Neurophysiology for Nch

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CONTRIBUTORS

Numbers in parentheses indicate the pages on which the author’s contribution(s) begin.

RICK ABBOT (219), Hyman-Newman Institute for Neurology and Neurosurgery,Beth Israel Medical Center, New York

RON L. ALTERMAN (405), Department of Neurosurgery, Hyman-NewmanInstitute for Neurology and Neurosurgery, Beth Israel Medical Center, New York

VAHE E. AMASSIAN (3), Departments of Physiology and Pharmacology, andNeurology, State University of New York, Health Science Center at Brooklyn,New York

ALBINO BRICOLO (267), Section of Neurosurgery, Department of NeurologicalSciences and Vision, Verona University, Verona, Italy

VEDRAN DELETIS (25, 197, 319), Division of Intraoperative Neurophysiology,Hyman-Newman Institute for Neurology and Neurosurgery, Beth Israel MedicalCenter, New York

FRED J. EPSTEIN (55, 319), Hyman-Newman Institute for Neurology andNeurosurgery, Beth Israel Medical Center, New York

LEO HAPPEL (169), Louisiana State University Medical Center, New Orleans,Louisiana

GEORGE I. JALLO (55), Hyman-Newman Institute for Neurology and Neuro-surgery, Beth Israel Medical Center, New York

DAVID KLINE (169), Louisiana State University Medical Center, New Orleans,Louisiana

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xii Contributors

KARL F. KOTHBAUER (73), Hyman-Newman Institute for Neurology andNeurosurgery, Beth Israel Medical Center, New York

MATEVZ J. KRZAN (153), Department of Neurology, Children’s Hospital,University Medical Center, Ljubljana, Slovenia

PATRICK MERTENS (93), Department of Neurosurgery, Hopital NeurologiquePierre Wertheimer, University of Lyon, Lyon, France

AAGE R. MØLLER (291), Callier Center for Communication Disorders,University of Texas at Dallas, Dallas, Texas

NOBUHITO MOROTA (319), Department of Neurosurgery, National Children’sMedical Center, National Center for Child Health and Development, Tokyo,Japan

GEORG NEULOH (339), Department of Neurosurgery, University of Bonn,Germany

YASUNARI NIIMI (119), Center for Endovascular Surgery, Hyman-NewmanInstitute for Neurology and Neurosurgery, Beth Israel Medical Center, New York

FRANCESCO SALA (119, 267), Section of Neurosurgery, Department of Neu-rological Sciences and Vision, Verona University, Verona, Italy

JOHANNES SCHRAMM (339), Department of Neurosurgery, University ofBonn, Germany

JAY L. SHILS (405), Division of Intraoperative Neurophysiology and Depart-ment of Neurosurgery, Hyman-Newman Institute for Neurology and Neuro-surgery, Beth Israel Medical Center, New York

MARC SINDOU (93), Department of Neurosurgery, Hopital NeurologiquePierre Wertheimer, University of Lyon, Lyon, France

TOD B. SLOAN (451), Department of Anesthesiology, University of TexasHealth Science Center, San Antonio, Texas

MICHELE TAGLIATI (405), Department of Neurology, Beth Israel MedicalCenter, New York

RICHARD J. TOLEIKIS (231), Department of Anesthesiology, Rush-Presbyterian-St. Luke’s Medical Center, Rush University, Chicago, Illinois

DAVID B. VODUSEK (197), University Institute of Clinical Neurophysiology,University Medical Centre, Ljubljana, Slovenia

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ACKNOWLEDGMENTS

Many thanks to David Hershberger and Marco Campos for their editorial help aswell as to Dr. Andrea Szelényi, Dr. Adauri Bueno de Camargo and Dr. Klaus Novakfor their careful review of the manuscript and for their insightful suggestions.

Special thanks to Linda and Carlos Schejola for their generous support whichhas given us the opportunity to build equipment for simultaneous recording ofneurophysiological and intraoperative neurosurgical data.

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PREFACE

Prior to the advent of current intraoperative neurophysiological monitoringmethodologies, it was difficult for neurosurgeons to determine the extent towhich a tumor, such as a low-grade malignancy spinal cord tumor, should beremoved. Ten years ago it was not uncommon for many patients, even those inwhom only partial tumor removal had been performed, to experience post-operative deficits like paraplegia or even quadriplegia.

Today, intraoperative neurophysiological (ION) methodologies for moni-toring the motor system can provide surgeons with real-time data that has beenshown to consistently correspond with post-operative motor status. Surgeonsnow have at their disposal a reliable criteria for determining the extent of tumorremoval and for preventing serious intraoperative neurological injury to themotor system.

This ability to ascertain the motor pathways’ functional integrity has becomeone of ION’s most important achievements, fulfilling its primary goals ofprevention and documentation of intraoperatively-induced neurological injury.As new ION methodologies develop, our ability to monitor and identify (map)different nervous system structures has also significantly evolved. Today, thewealth of data being drawn directly from exposed nervous tissue is rapidly cre-ating a second goal for ION: expanded exploration of the nervous system’sphysiology. Thanks to the introduction of these new methodological approaches,the pursuit of this goal promises to contribute new knowledge about parts ofthe nervous system which were previously inaccessible.

Since modern ION methodologies are finally providing reliable data con-cerning the integrity of the motor and other parts of the nervous system, it hasincreasingly become an important tool in several surgical disciplines. ION isnow an interdisciplinary field incorporating knowledge and experience fromneurosurgery, neurology, orthopedic surgery, neurophysiology, anesthesiol-ogy, interventional neuroradiology, and biomedical engineering.

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xiv Preface

Furthermore, new experiences in functional and stereotactic neurosurgeryfor the precise targeting of deep-brain structures and chronically implantabledeep-brain electrodes have refined the treatment of movement disorders.Precise physiological targeting now allows the neurosurgeon to access deepbrain areas where minor errors can make the difference between success andfailure.

Achievements in ION have been recognized by the neuroscience community(Clinical Examinations in Neurology, Mayo Clinic and Mayo Foundation, MosbyYear Book, 1991; Neurosurgery: The Scientific Basis of Clinical Practice, BlackwellScience Publ., 1998; Neuroprotective Agents, Annals of New York Academy ofScience, Vol. 939, 2001). Indeed, thanks to technological advancements and therapid growth of methodologies over the last ten years, we believe ION is tra-versing a fruitful and important period that will continue to strengthen andestablish its relevance in the medical community.

We are pleased to present 17 chapters dealing with current developments inION, most of them written by peer-recognized experts from around the world.We invite the reader to make extensive use of the accompanying CD at the endof the book, which provides video and audio/visual examples of some of themethodologies presented in the book. We believe that it is a powerful educa-tional and instructional tool.

We hope that this book will continue to stimulate interest in the integrationof ION into neurosurgery, and consequently, continue to decrease the numberof patients experiencing intraoperatively induced injury to the nervous system.

New York, NY Vedran DeletisSummer, 2002 Jay L. Shils

Cover image: Mrs. San-San Chiang, Senior Neurophysiological Technician,checking electrodes attached to a patient’s head which has been fixed in a frame.

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C H A P T E R 1

Animal and Human MotorSystem NeurophysiologyRelated to IntraoperativeMonitoringVAHE E. AMASSIAN

Departments of Physiology and Pharmacology, and Neurology, State University of New York, Health Science Center at Brooklyn, New York

1 Introduction2 Corticospinal Responses

2.1 Configuration of CT Waves2.2 Eliciting D Waves2.3 Eliciting I Waves

3 Muscle ResponsesReferences

ABSTRACT

This chapter uses data from animal models and human subjects to describe somephysiological principles underlying intraoperative spinal cord monitoring of themotor pathways. In the first type of monitoring, conducted impulses in the corti-cospinal tract (CT) are recorded following transcranial electrical stimulation (TES)or transcranial magnetic stimulation (TMS). Single pulses elicit direct (D), i.e., unre-layed CT discharges, which are followed, if the anesthesia is light, by multiple indi-rect (I) waves that are transsynaptically generated in motor cortex. Corticocorticalafferent inputs from parietal areas generate the first I wave, and subsequent I wavesresult from excitation by a vertically oriented interneuron chain in the motor cortex,which functions like a “clock” in quantizing time in periods of 1.3–2.0 ms.

The D wave increases in amplitude monotonically with TES or TMS intensity; overportions of the relation between stimulus intensity and D response, the curve is veryapproximately linear, so that a percent decrease during an operation approximatelyreflects a block in conduction proportionately in the number of conducting CT fibers.

By contrast, muscle activation by the CT volleys involves a highly nonlinear trans-fer function from CT to motoneuron, which may render this measure oversensitive

3Neurophysiology in Neurosurgery: A Modern Intraoperative ApproachCopyright 2002, Elsevier Science (USA). All rights of reproduction in any form reserved.

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4 Vahe E. Amassian

to CT damage. Anesthesia reduces not only tonic facilitatory bombardment of themotoneuron, but also I wave components, thereby diminishing temporal facilitationof the motoneuron. Cooling the motor cortex reduces, especially later, I waves andleads to loss of the muscle response. Such diminished excitation of the motoneuroncan be counteracted by using a high-frequency train of TES, which at the appropri-ate interstimulus interval can lead to excitatory postsynaptic potential (EPSP) sum-mation and motoneuron discharge.

1 INTRODUCTION

Monitoring motor responses for stimulating the human cerebral cortex hasclearly been used for much more than clinical mapping studies of the exposedbrain at operation [1]. The discovery that transcranial electrical stimulation(TES) of the human motor cortex could cause muscle activation [2] and itsreplacement in (awake) humans by the less painful transcranial magneticstimulation (TMS) greatly expanded the opportunities for motor pathway mon-itoring. The current uses include the following:

1. Intraoperative monitoring was the focus of this and other presentationsduring the symposium entitled “Intraoperative Neurophysiological Monitoringin Neurosurgery” (Second International Symposium in New York City, November20–21, 2000). Such recordings immediately affect surgical procedures and alsoaid in predicting outcome [3].

2. Preoperative mapping of motor representation, e.g., prior to cortical removalor implanting of a grid for cortical stimulation. The combination of surfacevisualization of the cerebral cortex with appropriate MRI software and mappingwith focal TMS appears especially advantageous [4].

3. Diagnosis and pathophysiological research, e.g., of lesions of the motorsystem such as those caused by multiple sclerosis, amyotrophic lateral sclero-sis, strokes, myoclonus, etc., have yielded unique data on central motor delays[5]. However, rarely has the clinical diagnosis depended on the electrophysio-logical monitoring. Rather, such monitoring has provided a quantitative func-tional measure of the effect of the lesion, which may assist in correlating theimaged extent of the lesion and the results of neurological examination. Such acomparison potentially aids in explaining the underlying pathophysiology ofmotor system disease and the changes in brain function, i.e., “reorganization”following lesions [4, 6, 7].

In intraoperative motor system monitoring, the physiological and patho-physiological mechanisms concern two types of response to stimulation of thecerebral cortex. The first, recorded from the corticospinal tract (CT), is rela-tively insensitive to anesthetic conditions and is “approximately” linearlyrelated to stimulus intensity, but it is of low amplitude, and the recordings often


Animal and Human Motor System Neurophysiology 5

include troublesome stimulus artifacts requiring special attention. In the secondtype of recording, the electromyography (EMG) of transcranially activated mus-cles is of greater amplitude than the CT response and therefore is easilyrecorded by widely used techniques, but it is highly sensitive to anesthetic leveland requires particular attention to the parameters of cortical stimulation, towhich it is nonlinearly related, and a high-frequency short train of stimuli isusually needed.

2 CORTICOSPINAL RESPONSES

2.1 CONFIGURATION OF CT WAVES

2.1.1 Conducted Impulses

Soon after population-conducted impulses were recorded in cats and monkeys,it was apparent that recordings from the surface of the medullar pyramid or thedorsum of the spinal cord differed markedly from those among the CT fibers[8]. With single electrical pulse stimulation of the motor cortex, recordingsfrom the pial surface reveal a brief positive–larger negative deflection of thewave, whose latency is clearly accounted for by conduction time in fast CTfibers; i.e., the wave is direct (D) without intervening synapses (Fig. 1.1, left).

FIGURE 1.1 Conducted and blocked D and I responses in squirrel monkey and conductedresponses in humans. Left, indicated number of summed CT responses to motor cortical stimula-tion. Monkey anesthetized with pentobarbital. Middle and right, epidural recordings from humansat indicated cervical level; TMS stimulation was oriented to induce either a lateromedial (L-M) orpostero-anterior (P-A) electric field. At left, CT response increases in amplitude many-fold whenconducted response is blocked. On the right, interrupted lines indicate the “correction” factorapplied to I waves relative to D waves recorded in humans. Absolute amplitude of all waves wouldincrease. Left records reprinted from [10]; middle and right records reprinted from [11].


6 Vahe E. Amassian

Following the D wave are less well defined and usually much smaller waves,which upon appropriate analysis (see Section 2.3) were proved to be indirect(I), being CT fiber discharges following transsynaptic activation in motorcortex. Depending on the parameters of cortical stimulation, such conducted Dwaves, with or without I discharges, constitute the great majority of epiduralrecordings in humans. The explanation for the D wave configuration readilyderives from classical volume conductor theory. When the focal recording isreferenced against a “distant” electrode, the approach of an impulse in each CTfiber is signaled by an initial positivity; the isoelectric transition signals thearrival of the impulse, and the subsequent negativity results from fiber activa-tion under the focal electrode. Finally, propagation of the impulse beyond thefocal electrode with recovery toward the resting potential yields a low-amplitude,long-duration positivity. Whereas in animal preparations the final positivitymay be barely distinguishable, in human D recordings it is usually more promi-nent than the initial positivity, even when differentiation of the preceding neg-ativity is avoided by using an adequate band pass at the low-frequency end [9].Thus, given the triphasic potential associated with single CT fiber recordings,the amplitude of the population D wave reflects a number of factors: (1) Thefirst of these is the synchronicity of the potentials in each fiber; slowing of con-duction velocity in part of the responding population would lead to additionalreduction in peak amplitude through phase cancellation. A reduced D waveamplitude accompanied by a broadening of the negative component might evi-dence diminished synchronization. (2) The second factor is the number of acti-vated, fast CT fibers. (3) The action potential amplitude in individual fibers maybe changed by physiological phenomena such as refractoriness or supernor-mality [9] or by damage.

2.1.2 Blocked Impulses

When a semi-microelectrode is inserted into the CT (or pyramid), the config-uration of the D wave is markedly altered (Fig. 1.1, left). The polarity of the Dwave becomes substantially monophasic with a duration approximating theprevious (+ − +) wave [10]. The blocked region acts only as a source for theapproaching sink, or more accurately, the injury potential is briefly reduced.Furthermore, the amplitude of the D wave substantially increases (nearly 5 ×in Fig. 1.1). However, a much greater increase in amplitude (× 15.5) of the Iwave is recorded; i.e., a threefold increase in the I:D ratio can occur when a con-ducted CT response is blocked. In Fig. 1.1, right, this “correction” factor isapplied to conducted human CT responses [11]. Such a relative increase in theamplitude of a blocked response is usually attributed to lessened phase cancel-lation of slightly asynchronous triphasic potentials when these are converted by



block to monophasic potentials; although this may be an important factor, itmay not be the only factor [12].

The recording of a monophasic D wave provides a basis for constructingrelationships between stimulus intensity and D wave response [13]. Electricalstimulation of the subcortical white matter at increasing intensity yields amonotonic relationship to the D wave amplitude (Fig. 1.2). Theoretically, agroup of fast CT fibers, with diameters (and therefore thresholds) normally dis-tributed around a mean value, would, exposed to the same electrical stimulus,yield a sigmoid relation (i.e., the integral of the normal distribution function)between stimulus intensity and population D response. Experimentally, the Dwave response only approximates a sigmoid function. However, the CT in cats,monkeys, and humans contains a wide range of fiber diameters, and an electri-cal stimulus in the white matter cannot be expected to affect fibers uniformly;although the largest CT fibers that were closest to the stimulating electrodeswould first be excited, at increasing intensities nearby higher-threshold fibersand distant low-threshold fibers (subject to an inverse square reduction inintensity) would both be stimulated. Further complicating the stimulus-response relationship is that the lowest threshold CT fibers first excited wouldbe expected to contribute the largest action potentials to the populationresponse. Thus the amplitude of the population D wave only approximatelymeasures the number of synchronously active fibers (cf. the EMG response).With magnetic stimulation (Fig. 1.3), the large stimulus artifact precludes elic-iting a maximum D wave, but at submaximal stimulus intensities, the D waveclearly increases monotonically [10] in the “quasilinear” manner of the inter-mediate range of intensities in Fig. 1.2 [13].

Given that insertion of a recording electrode into the human CT would notbe justifiable in routine monitoring, the question arises as to whether there areany serious disadvantages in being restricted to recording conducted responses.

FIGURE 1.2 Relationship of electrical stimulus intensity to PT D wave amplitude. Subcorticalwhite matter of cat stimulated with 0.19 ms pulses at indicated current strengths via bipolar elec-trodes. Reprinted from [13].


8 Vahe E. Amassian

Clearly, the normal conducted D wave amplitude remains a valuable measureof the number of conducting fibers, limited only by the factor of pathologicaldesynchronization and reduced action potential amplitude in the individualfibers. However, the major reduction in I:D wave amplitude ratio renders con-ducted CT activity a technically unacceptable measure of thresholds of D and Iactivation with focal anodal versus cathodal stimulation or electrical versusmagnetic stimulation.

The conversion toward a monophasic potential with fiber injury permits afunctional identification of the site of experimental traumatic injury to thespinal cord [15], which can be compared with the rostral limit of the contusion(Fig. 1.4). A similar change toward positivity was caused by a spinal cord tumor[16]. It would be valuable to record the potential changes in the epi- or subduralD wave when recorded at several levels (i.e., above, at, or just below a trauma-tized level of spinal cord), to compare the “electrophysiological” level with theMRI and neurological levels. Such measurements would also serve to validateapplying to the human the I/D amplitude correction for blocked CT impulsesdeduced from the monkey (Fig. 1.1, right).

2.2 ELICITING D WAVES

Transient electrical stimulation of motor cortex in animals and human readilyelicits D activation, but there are important differences in the efficacies andsites of activation related to the intensity, the polarity (+ or −) of the focal stim-ulus, and the species. In cats, the CT neuron may be excited at three sites: at theinitial segment (IS) region and adjoining membrane, at its recurrent axon collat-erals (with increased latency through slowed propagation), and in white matter.

FIGURE 1.3 Effect of changing TMS stimulus intensity on CT D wave responses. Monkey main-tained under pentobarbital anesthesia. Round coil (9.4 cm outer diameter) in lateral-sagittal posi-tion so one set of windings over CT projections. One hundred percent output equivalent to 2.2 T.Five responses superimposed on each trace. Reprinted from [14].



Hern et al. [17] described in monkeys that focal anodal stimulation could elicitD excitation alone in conducted impulse recordings; however, later recordingsof blocked CT fibers revealed that when the stimuli were a little above thresh-old (e.g., 50%), both D and I waves were elicited by either polarity of stimula-tion [10]. Nevertheless, in the monkey, focal anodal and cathodal stimulationgenerates D waves at different sites; with cathodal stimulation, at a given inten-sity D waves are highly variable, while they are almost constant in amplitudewith anodal stimulation (Fig. 1.5). Presumably, with cathodal stimulation, Dactivation can occur close to the spike trigger zone, e.g., at the IS and adjoiningmembrane, while with anodal stimulation, it occurs at a white matter site elec-trotonically isolated from the synapses. Intracellular recording in the cat sup-ports this explanation, threshold bipolar stimulation generating a D impulsewhen CT and other motor cortical neurons are relatively depolarized (Fig. 1.6);when less depolarized, transsynaptic excitation was necessary [18].

The site within white matter where focal anodal stimulation elicits D activa-tion at the lowest threshold is now believed from modeling studies to be atbends in the CT fibers [19, 20]. Facilitation occurs when just threshold inten-sities of anodal TES and TMS are combined only at brief intervals (e.g., 30 µs;[21]). The site of electrotonic summation of the two stimuli is inferred to be at

FIGURE 1.4 Effect of weight drop on spinal cord and on feline CT response recorded epidurallyat indicated distances above the contused area in photograph. Cat anesthetized with pentobarbital.Weight drop was 47 g × 7.2 cm, producing a 96% block in conduction. Effect of impact occurswithin 1 s, precluding vascular factors or edema in the loss of conduction. Two hundred responsessummed on each trace. Reprinted from [15].


10 Vahe E. Amassian

FIGURE 1.5 Effect of changing surface anodal and cathodal stimulus intensities on CT responses.Squirrel monkey lightly anesthetized with pentobarbital, three superimposed responses on eachtrace. Reprinted from [10].

FIGURE 1.6 Relationship of site of D activation to membrane potential of PT neuron. At right,intracellular recording of PT neuron, which follows 1:1 at 500 Hz antidromic stimulation. (A) and(B) show latency variation with threshold stimulation at motor cortical sites A and B. (C) column isan intensity series. (D) shows clear onset of EPSP. Middle, above shows latency of first discharge plot-ted as a function of membrane potential; below, latency distributions with stimulation at sites A andB. At left, arrows in diagram show excitation at IS-axon hillock region, at recurrent collateral (initialdischarge in middle, bottom histogram) and at bend in fiber in white matter. Reprinted from [18].



bends of CT fibers in the white matter, where the directions of the orthogonalelectric fields would both lead to outward current from the node.

What implication do these findings have in the human? The great majorityof conducted D wave recordings will depend on TES, rather than stimulatingthe surgically exposed pial surface of motor cortex. Necessarily, the electricfield is developed over a wide area of cortex and subcortex because the closerthe interpolar distance, the greater the proportion of current shunted throughthe superficial tissues. Given the high resistance of the cranium, there seems noadvantage in using electrodes with small surface areas. Our standard techniqueuses a focal scalp electrode (dimension: 2 × 2 cm), over motor cortex, with alarge semicircular reference electrode (area: 25 cm2) at an interpolar distanceof approximately 6 cm [22]. Muscle responses during voluntary contraction areobtained at a higher threshold with focal cathodal than with anodal TES, butthe increased current strengths required are greater than expected from the dif-ferences in D threshold in monkeys or in humans [23]. Monitoring stimulatingcurrent, e.g., by an inductive probe on a stimulating lead (P6016, Tektronix,Inc., Beverton, OR), is valuable in monitoring stimulus intensity. Electrodeimpedances are readily assessed by substituting for the subject an appropriateprecision resistor (e.g., 1 KΩ); the electrode impedances are then calculatedfrom the ratio in currents flowing at the given voltage output of the stimulator.Initially, 25 µm-thick stainless steel electrodes were used, but these provedunsuitable because if bent, they no longer conformed to the scalp; aluminumfoil has proved a satisfactory substitute because it is easily flattened and doesnot distort brief electrical stimulating pulses (e.g., 0.2 ms in duration).

Practical considerations may require specific stimulating electrode montagesappropriate for the requirements of a particular group of patients (cf. the useof Corkscrew electrodes, Nicolet, Madison, WI [9]). The sites of stimulationC3 vs. C4 are of particular interest because of the likelihood of D excitationat both sites at the stimulus intensities used; this excitation increases the sizeof the CT D wave through summation. A possible problem could arise if thecombined D wave amplitude fell by x% due to unilateral pressure on one lateralcolumn and actually resulted from twofold damage to that column. A suggestedmontage to identify such a problem would be to connect the (−) output of thestimulator to the posteriorly sited large reference electrode and the (+) outputto a two-pole, three-way switch permitting a connection to (1) both focalanodes; (2) the right anode; and (3) the left anode. Alternatively, if a focalanodal pulse were delivered 1 ms after the first pulse at the same site, the CTfibers would be in the refractory period [9]. Therefore, focal anodic stimuligiven at C3 and C4 1 ms apart should generate independent D waves.

The initial animal experiments on the CT were all conducted under varyinglevels of barbiturate or chloralose anesthesia, without any description of anes-thetic effects on the D wave amplitude. However, it is evident that an increased


12 Vahe E. Amassian

anesthetic level could reduce D wave amplitude of cathodally elicited responsesif the level of a net steady-state facilitatory bombardment of CT neurons weredepressed. Unfortunately, there is no evidence in humans that focal cathodal(or anodal) stimuli preferentially excite CT neurons in the grey matter wheretranssynaptic conditioning effects could occur. On the contrary, the earliest Dwave recordings indicated increasingly subcortical sites of excitation withincreasing focal anodic stimulus intensities [24–26]. Therefore, the reporteddepression of CT responses to anodal TES excitation at higher anesthetic levelswould reflect either a direct effect on CT fibers [25] or an indirect effect, e.g.,through anesthetic-induced redistribution of fluids and therefore of stimulatingcurrents within the brain [12]. Significantly, the anesthetic mediated effect onD wave amplitude under 2% isofluoride caused a reduction to 46% with TES,but only to 80% with stimulation of the exposed motor cortex. Furthermore, anincreased level of anesthesia increases the latency of the CT response to TES,thereby supporting the hypothesis that the site of TES stimulation shifts withanesthetic level.

The above account has focused on the use of TES rather than TMS in elicit-ing D waves, although it has long been known that the appropriate lateral ori-entation of the coil can elicit muscle responses with latencies matching thosewith focal anodic TES [22, 27]. Proof of preferential direct CT excitation withthe appropriate orientation of the coil was secured in the monkey [14] and inhumans [11]. Although there appears to be little advantage of TMS over TESduring surgery, the use of TMS facilitates preoperative tests on the same patientprior to anesthesia.

2.3 ELICITING I WAVES

The monumental Golgi studies of connectivity in cerebral cortex by Lorente de Nó[28] led to the hypothesis that repetitive I waves result from excitatory bom-bardment of CT neurons by interneuron chains [8]. Subsequently, other mech-anisms have been proposed, which will be briefly reviewed later in this section.

Many powerful synaptic inputs impinge either directly or indirectly on large CTneurons, including (1) extrinsic inputs from (a) inter-areal corticocortical afferents,(b) callosal afferents, and (c) specific thalamocortical afferents; and (2) intrinsicinputs from local motor cortical neurons. A difficulty in analyzing the sourceof transsynaptic excitation of CT neurons when electrical (or magnetic) stim-uli are applied over the motor cortex is not knowing whether the CT neuronsrespond to one or other of the extrinsic inputs or to an intrinsic input. In thefollowing account, it is presumed that if I waves are elicited by distant corticalstimulation, they are most likely generated by corticocortical inputs; if loss orproduction of particular I waves occurs selectively with procedures applied


Animal and Human Motor System Neurophysiology 1 3

locally to motor cortex, such as cooling or microelectrode stimulation, thenintrinsic inputs may elicit such I waves.

2.3.1 Extrinsic Inputs

Among powerful extrinsic inputs, some can readily be eliminated as necessaryfor generating I waves. Thus excitation of specific thalamocortical afferentsderived from Nucleus ventralis lateralis (VL) and anterior (VA), which aremono- and disynaptically excitatory to large CT neurons, and those fromNucleus ventralis posterior (VP), which are polysynaptically excitatory [ 291,was eliminated in cats by massive radio frequency lesions of these thalamicnuclei. After allowing lo-27 days for degeneration of the afferent fibers, I acti-vation of pyramidal tract (PT) fibers was still obtainable with pericruciate stim-ulation of motor cortex [lo]. It would clearly be of interest to stimulate motorcortex with TMS in patients who previously had unilateral Nucleus VL-VAlesions for Parkinsonism to determine if the threshold for motor responses wasunelevated.

Among corticocortical inputs, those in the human from the contralateralhemisphere clearly can have excitatory effects, as when visual information isprojected onto the nondominant hemisphere and subsequently transferredtranscallosally for vocalization. However, the predominant transcallosal effectof single-pulse TMS is inhibitory [30]. By contrast, large multiple I waves werereadily elicited in monkey CT by electrical stimulation of parietal or premotorcortex (Fig. 1.7 [8,31]). In humans, facilitatory interaction between combinednear-threshold parietal and premotor cortical TMS is elicited at time intervalsexcluding any direct summation of the electric fields [32]. Therefore, the TMSand most likely TES over motor cortex most likely elicit multiple I waveresponses through generat ing an incoming vol ley in cort icocort ica l a f ferent f ibers .

BEFORE ABLATION

AFTER MOTOR CORTICAL ABLATION

FIGURE 1.7 Corticospinal responses in monkey to electrical stimulation of cortical loci before(above) and after (below) precentral ablation. The inset shows only D response when white matterexposed by ablation is stimulated. Reprinted from [31].

14 Vahe E. Amassian

Significantly, when the lateral windings of a circular coil centered on the vertexoverlie motor cortex, muscle activation occurs a minimum of 1–2 ms later thanwith focal anodic stimulation; the later activation by TMS is manifest also insingle motor unit recordings; i.e., it does not reflect activation of slowermotoneurons but their activation by I discharge [33]. With TMS appliedthrough a figure 8 coil, optimal motor response occurs when the midpoint of thejunction region of a figure 8 coil is close to the interaural line, i.e., over motorcortex and approximately at 90° to the central sulcus [34, 35]. The failure ofsingle-pulse TMS, applied parasagittally over motor cortex, to excite directly thelargest neurons in motor cortex, the Betz cells, which lie in a variety of orien-tations in the banks and crown of the folds of the precentral gyrus, makes it veryunlikely that smaller neurons are directly excited. Modeling experiments witha peripheral nerve in a skull volume conductor [19] implies that excitationwould preferentially occur at the bend in the corticocortical fibers toward greymatter. Excitation occurs at a bend optimally by the induced electric field at itspeak and not at its spatial derivative, as with a linear nerve [20]. As indicatedpreviously, optimal TMS parasagittal excitation occurs when the center of thejunction region, i.e., the peak electric field, is over motor cortex. Furthermore,optimal TMS excitation occurs when the direction of the induced electric fieldis posterior-anterior (P-A) [27, 33], i.e., appropriate for current exiting thebend of parietal corticocortical fibers. Responses from corticocortical fibersfrom more anterior portions of the frontal lobe, such as Area 6, are optimallyelicited when the induced field is A-P directed, i.e., exiting the bend of the pos-teriorly directed afferent fibers.

It must be emphasized that the difficulty of TMS in directly exciting neu-ropil in grey matter applies only to single stimuli. For example, when a near-threshold TMS pulse applied in the P-A orientation over motor cortex is briefly(e.g., 1–2 ms) followed by a weaker second pulse, (e.g., 70% of the intensity ofthe first), the first dorsal interosseous (FDI) response is markedly facilitated[36, 37]. Because the corticocortical fibers excited by the larger first TMS pulsewould be refractory to the even weaker second pulse, other neural elements whosethreshold was reduced by the transsynaptic effect of the first pulse most likelymediated the facilitation. A likely site where the electric field induced by thesecond TMS pulse and EPSPs from corticocortical action of the first could interactis the initial segment and adjoining membrane of the motor cortical neurons.

A major question that arises is whether the multiple I waves result from thetranssynaptic conductance changes induced by a single volley in thalamocorti-cal [38] or corticocortical fibers, or whether they reflect excitation by intrinsicmotor cortical neurons or a combination of both monosynaptic (corticocortical)and polysynaptic (local interneuronal) excitations. Clearly, invoking monosy-naptic activation of CT neurons by a synaptic input requires recording the min-imum EPSP delays and attaining subsequent delays for firing level in PT neurons


16 Vahe E. Amassian

unlikely that a prolonged conductance change alone generates the I waves. Fur-thermore, in humans, two near-threshold TMS pulses presented at intervalsthat are harmonics of the I wave periodicity yield optimal facilitation of FDIresponses [43]. With four near-threshold TMS pulses, a “tuning” curve (Fig. 1.8)of FDI facilitation was demonstrated, which peaked at an interstimulus inter-val of 1.3–1.7 ms in the four subjects tested. By contrast, facilitation tested inone of these subjects with four focal anodic stimuli was absent at 1.7 ms butprominent at 2.7 ms, indicating that the preferred timing of facilitation withTMS depends on motor cortical rather than spinal cord circuitry [12].

(b) Microelectrode stimulation at different depths within monkey motorcortex preferentially elicits late I waves superficially; early I waves are addedwhen the stimulation is in the deeper laminae (Fig. 1.9, middle). In cat andmonkey, bipolar microwire stimulation that generates an electric field with amajor transverse component elicits an I1 wave when close to lamina V (Fig. 1.10),possibly through stimulation of axons in the inner line of Baillarger [10].

(c) Cooling the pial surface of monkey motor cortex selectively causes thereversible loss of late I waves without reducing the earliest I wave (Fig. 1.9,right). Taken together, (b) and (c) imply that the excitatory motor cortical neu-rons are vertically oriented, as was earlier inferred by Lorente de Nó [28].

The differing latencies of, e.g., FDI response with P-A versus A-P orientedTMS pose a problem because of the descriptions of corticocortical afferents as

FIGURE 1.9 Differential effects on initial versus later I waves in monkey. Middle, microelectrodestimulation at indicated depth in motor cortex elicits later I waves superficially (with D wave).Right, progressive cooling nearly abolishes later I waves, but not I1. Left, diagram of possible verti-cally oriented, excitatory interneuron circuit, which may underlie the multiple I waves. Left dia-gram reprinted from [12]; middle records from [8]; right records from [10].



terminating throughout the laminae [28, 44, 45]. One possibility is that cortico-cortical inputs from parietal lobe and premotor cortex do not similarly terminatein all laminae; e.g., Jones et al. [46] described corticocortical afferents as ter-minating only in the superficial laminae of neighboring somatosensory cortex,and Chang [47] described both callosal and association corticocortical fibers asterminating in the superficial laminae. Alternatively, the classical descriptionsof the site of termination may apply to motor cortex, but the synaptic efficaciesof deeper termination may not be adequate for monosynaptic (I1) activationfrom premotor sources.

A final comment on the possible function of the motor cortical interneu-ronal circuitry is warranted, given the present focus on human spinal cordmonitoring. We have previously proposed that the multiple high-frequencyI waves function in a manner analogous to a computer clock, quantizing cor-tical time [10]. Nowhere is the synchronization of CT discharges at a rela-tively fixed period so remarkable as in human I waves recorded at greatconduction distance from the motor cortical circuitry that generates the period[25, 48].

FIGURE 1.10 Monosynaptic (I1) excitation in monkey and cat by bipolar microwire stimulationin deep laminae. Stimulation throughout the Teflon-insulated, adjoining 50 µm wires generated anelectric field that was mainly tangentially oriented. Five responses superimposed in each trace atthe indicated depth of stimulation. Left, monkey motor cortex penetrated at an angle of 55° fromthe radial axis. Marking lesion made at optimal site (4.9 mm) was found in the histological sectionto be just deep to lamina V. Middle, cat pericruciate cortex stimulated at indicated depth. Record-ings from the corticospinal tract showed optimal I1 with small D wave at 1.5 mm depth; histolog-ical section indicated that this depth was below lamina V. Right, pericruciate cortex of another catstimulated with recording from medullary pyramid. Top of marking lesion at optimal site (1.5 mm)for I1 just below lamina V. Reprinted from [10].


18 Vahe E. Amassian

3 MUSCLE RESPONSES

With the discovery by Merton et al. [2] that single-pulse TES in the awakehuman could elicit a muscle response in voluntarily contracting muscle, thequestion arises as to the necessary relationship between CT and motoneurondischarges. Brookhart [49] had earlier emphasized the role of temporal facili-tation in cats and monkeys in eliciting motor responses by a train of electricalstimuli to the medullary pyramid. While anodal TES at high intensity would beexpected to add I waves to the initial D discharge from a single-pulse TES (seeSection 2), this seems not to be the crucial factor in eliciting the muscleresponse in the awake human, because the short latency of the response reflectsD and not later I activation. The critical factors in the muscle response are thesize of the D volley, i.e., the degree of spatial facilitation and how close to thefiring level of the α-motoneurons are their membrane potentials. In the anes-thetized patient, the background depolarization from voluntary activity must bereplaced by another source, i.e., temporal facilitation that is achievable by atrain of CT volleys.

The basis of temporal facilitation by a train of CT volleys was shown byPhillips and Porter [50] in intracellular recordings from baboon α-motoneuronsto result from summation of successive EPSPs that mount to the firing level.Unfortunately, in their experiments, the anodal motor cortical stimuli, in addi-tion to the train of D volleys, elicited also I discharges because of facilitation atthe cortical level [51]. (Evidently, the component of temporal facilitation at themotoneuron would best be estimated by stimulation at the level of the medullarypyramid.) Nevertheless, temporal summation of EPSPs is clearly of majorimportance in securing motoneuron discharge. The length of the CT train ofvolleys determines whether the mounting EPSPs actually reach firing level.Thus selectively reducing the latest I activity by cooling the pial surface ofmonkey motor cortex abolishes the muscle response (Fig. 1.11).

Temporal facilitation during spinal cord monitoring could be secured byeither a train of stimuli each eliciting a D volley, or potentially with fewer stim-uli but each generating a D volley plus repetitive I waves. A major determinantin the human of the amplitude of I wave responses is the level of anesthesia [25,26, 51]. Thus, under deep anesthesia, temporal facilitation can only be securedby a train of D volleys. It must be emphasized that increasing the depth of anes-thesia would reduce not only I activity but also tonic facilitatory bombardmentof α-motoneurons and therefore reflex responses to a given sensory stimu-lus. The optimal period in a train of D volleys for activating muscle is a resul-tant of several factors. If the period is too long, the EPSPs will have largelydecayed before the next CT volley arrives; if too short, refractoriness reduces thesize of the CT volley. However, refractoriness would be absent at a period of 4 msand even at the shorter period with a long-duration (e.g., 0.5 ms) TES pulse [9].



The deeper the anesthesia, the longer would be the duration of the motoneu-ron membrane time constant because of the reduced resting conductance level.Thus, with an approximate decay time constant unlikely to be less than 4 ms,a 250 Hz train would still provide substantial facilitation.

Under light anesthesia, when the D wave is followed by multiple I waves,optimal conditions for temporal facilitations would be determined by additionalfactors. The I wave period is often as brief as 1.4 ms, probably because EPSPsat the spike trigger zone overcome relative refractoriness from the previousaction potential. In addition, I activation is known to occur in CT neurons thatwere not previously D activated [8, 18] or were activated after a double I period[14]. The optimal interstimulus period would be determined by the duration ofthe combined D and multiple I waves discharges, which is likely to exceed 5 ms.Little would be gained by using a shorter interstimulus period, because ofocclusion between D and I waves with those from an antecedent stimulus.

Another major difference between monitoring muscle versus CT response isthe nonlinear relationship between TES intensity and the muscle response. Inthe monkey, the muscle response appears abruptly with a small increase instimulus intensity and CT response (Fig. 1.12). As a result, the muscle responseis potentially more sensitive to spinal cord damage than the CT response, notonly because of the transfer function from the CT volleys to motoneurons, but

FIGURE 1.11 The effect of cooling the pial surface of the motor cortex on paired corticospinal Dwith multiple I waves (above) and thenar muscle responses (below) in monkeys. Three responsessuperimposed in each trace. First series (bottom left) was taken immediately after the onset of cool-ing; second series (top right) was started 35 s later; third series (bottom right) was taken immedi-ately after the second. Reprinted from [10].


20 Vahe E. Amassian

also because a reduction in tonic facilitation may reduce the efficacy of the CTvolleys still further.

Finally, it should be noted that important aspects of the relationship of CTactivity to motoneuron discharge require investigation at the cellular level. Forexample, it is unknown when repetitive CT volleys in the same presynapticfibers fail to maintain quantal transmitter release, or even invade terminals asstudied at group Ia endings [52]. At rates where failure occurs, increasing inten-sity during a TES train would, by recruiting additional presynaptic fibers, pro-vide spatial facilitation, thereby increasing the efficiency of stimulation for agiven total charge administered.

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FIGURE 1.12 The effect of increasing stimulus intensity applied to motor cortex of monkey on cor-ticospinal D and I waves and thenar muscle EMG responses. Ten responses superimposed in eachtrace. Anesthesia was pentobarbital. The bipolar stimulus (duration 100 µs) was applied at the indi-cated current strength to the optimal cortical site for thenar muscle responses. Reprinted from [10].



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25. Burke, D., Hicks, R.G., and Stephen, P.H. (1990). Corticospinal volleys evoked by anodal andcathodal stimulation to the human motor cortex. J. Physiol., 425, 283–299.

26. Burke, D., Hicks, R., Gandevia, S.C., Stephen, J., Woodforth, I., and Crawford, M. (1993).Direct comparison of corticospinal volleys in human subjects to transcranial magnetic andelectrical stimulation. J. Physiol., 470, 383–393.

27. Werhahn, K.J., Fong, J.K., Meyer, B.U., Priori, A., Rothwell, J.C., Day, B.L., and Thompson,P.D. (1994). The effect of magnetic coil orientation on the latency of surface EMG and singlemotor unit responses in the first dorsal interosseous muscle. Electroencephalogr. Clin. Neuro-physiol., 93, 138–146.

28. Lorente de Nó, R. (1943). Cerebral cortex: Architecture, intracortical connections, motorprojections. In “Physiology of the nervous system” (J.F. Fulton, ed.). Oxford University Press,New York.

29. Amassian, V.E., and Weiner, H. (1966). Monosynaptic and polysynaptic activation of pyrami-dal tract neurons by thalamic stimulation. In “The thalamus” (D.P. Purpura, and M.D. Yahr,eds.), pp. 255–282. Columbia University Press, New York.

30. Ferbert, A., Priori, A., Rothwell, J.C., Day, B.L., Colebatch, J.G., and Marsden, C.D. (1992).Interhemispheric inhibition of the human motor cortex. J. Physiol., 453, 525–546.

31. Patton, H.D., and Amassian, V.E. (1960). The pyramidal tract: Its excitation and functions. In“Handbook of physiology” (J. Field, ed.), section 1, vol. 2, pp. 837–861. American PhysiologicalSociety, Washington, D.C.

32. Amassian, V.E., Cracco, R.Q., Maccabee, P.J., Vergara, M., Hassan, N, Eberle, L., and Rothwell,J.C. (1997). Spatial facilitation of human motor responses by near-threshold magnetic stimu-lation of parietal and frontal areas. J. Physiol., 504P, 115P.

33. Rothwell, J.C., Thompson, P.D., Day, B.L., Boyd, S., and Marsden, C.D. (1991). Stimulation ofthe human motor cortex through the scalp. Exp. Physiol., 76, 159–200.

34. Mills, K.R., Boniface, S.J., and Schubert, M. (1992). Magnetic brain stimulation with a doublecoil: The importance of coil orientation. Electroencephalogr. Clin. Neurophysiol., 85, 17–21.

35. Sakai, K., Ugawa, Y., Terao, Y., Hanajima, R., Furabayashi, T., and Kanazawa, I. (1997). Pref-erential activation of different I waves by transcranial magnetic stimulation with a figure-of-eight shaped coil. Exp. Brain Res., 113, 24–32.

36. Ziemann, U., Tergau, F., Wassermann, E.M., Wischer, S., Hildebrandt, J., and Paulus, W.(1998). Demonstration of facilitatory I wave interaction in the human motor cortex by pairedtranscranial magnetic stimulation. J. Physiol., 511, 181–190.

37. Amassian, V.E., Rothwell, J.C., Cracco, R.Q., Maccabee, P.J., Vergara, M., Hassan, N., andEberle, L. (1998). What is excited by near-threshold twin magnetic stimuli over human cere-bral cortex? J. Physiol., 506P, 122P.



38. Phillips, C.G. (1987). Epicortical electrical mapping of motor areas in primates: Motor areas ofthe cerebral cortex. In “Ciba symposium 132” (G. Bock, M. O’Connor, and J. Marsh, eds.), pp.5–16. Wiley, Chichester.

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43. Tokimura, H., Ridding, M.C., Tokimura, Y., Amassian, V.E., and Rothwell, J.C. (1996). Shortlatency facilitation between pairs of threshold magnetic stimuli applied to human motor cotex.Electroencephalogr. Clin. Neurophysiol., 101, 263–272.

44. Goldman, P.S., and Nauta, W.J.H. (1977). Columnar distribution of cortico-cortical fibers inthe frontal association, limbic and motor cortex of the developing rhesus monkey. Br. Res., 122,393–413.

45. Szentagothai, J. (1978). The neuron network of the cerebral cortex: A functional interpretation.Proc. Roy. Soc. Lond., B201, 219–248.

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48. Deletis, V. (1993). Intraoperative monitoring of the functional integrity of the motor path-ways. In “Advances in neurology: electrical and magnetic stimulation of the brain” (O. Devinsky,A. Beric, and M. Dogali, eds.), pp. 201–214. Raven Press, New York.

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C H A P T E R 2

IntraoperativeNeurophysiologyand MethodologiesUsed to Monitor theFunctional Integrityof the Motor SystemVEDRAN DELETIS

Division of Intraoperative Neurophysiology, Hyman-Newman Institute for Neurologyand Neurosurgery, Beth Israel Medical Center, New York

1 Intraoperative Monitoring of the Motor System:A Brief History1.1 Penfield’s Time1.2 Spinal Cord to Spinal Cord1.3 Spinal Cord to Peripheral Nerve (Muscle)

2 New Methodologies2.1 Single-Pulse Stimulation Technique2.2 Multipulse Stimulation Technique

3 Methodological Aspects of TES During GeneralAnesthesia3.1 Electrode Montage Over the Scalp for Eliciting

MEPs (for Single- and Multipulse StimulationTechniques)

4 Recording of MEPs over the Spinal Cord (Epiduraland Subdural Space) Using Single-PulseStimulation Technique4.1 D Wave Recording Technique Through an

Epidurally or Subdurally Inserted Electrode4.2 Proper Placement of Epidural Electrodes



26 Vedran Deletis

4.3 Factors Influencing D and I Wave Recordings 4.4 Neurophysiological Mechanisms Leading to the

Desynchronization of the D Wave5 Recording of MEPs in Limb Muscles Elicited by a

Multipulse Stimulating Technique5.1 Selection of Optimal Muscles in Upper and Lower

Extremities for MEP Recordings5.2 Neurophysiological Mechanisms for Eliciting

MEPs using a Multipulse Stimulation Technique5.3 Surgically Induced Transient Paraplegia

6 ConclusionReferences

ABSTRACT

Beginning with Penfield’s early work and covering the latest developments in thefield, this chapter will present a brief history of intraoperative neurophysiology of themotor system, paying special attention to the use of motor evoked potentials (MEPs)during surgeries that place the motor system at risk of injury. The chapter will assessthe advantages and disadvantages of traditional techniques previously used to mon-itor the corticospinal tract (CT), discuss modern methodologies for eliciting andrecording MEPs (single and/or multipulse, transcranially applied, electrical stimu-lation, with recorded activity from either the spinal cord or from the limb muscles),and assess the neurophysiological background for both sets of techniques. Particu-lar interest will be placed on the intraoperative changes of MEPs, their relationshipto neurological outcome, and their potential neurophysiological explanations. As anexample, the phenomenon of surgically induced transient paraplegia, and thechanges in monitoring parameters accompanying it, will be discussed.

1 INTRAOPERATIVE MONITORINGOF THE MOTOR SYSTEM: A BRIEF HISTORY

1.1 PENFIELD’S TIME

When discussing the use of intraoperative electrical stimulation of the uppermotoneurons in humans, it is essential to mention Wilder Penfield (1891– 1976).His publication with Edwin Boldrey in the journal Brain [1] summarized hiswork on the motor and somatosensory system’s organization of the cerebralcortex in humans, as explored with intraoperative electrical stimulation. Penfield’ssystematic exploration of the brain with intraoperative stimulation laid thefoundation for the field of intraoperative neurophysiology (ION).

After Penfield—except for the work done to intraoperatively localize epilep-tic foci—almost half a century passed without any significant developments in


Intraoperative Neurophysiology and Methodologies 27

ION exploration of the nervous system. However, a transformation took placeduring the 1950s and the 1960s when clinical neurophysiology branched intothree subfields: electromyography (EMG), electroencephalography (EEG), andevoked potentials. These developments helped to widen the doors of the oper-ating room to the use of these methods intraoperatively.

By the late 1970s, somatosensory evoked potentials (SEPs) became routinelyused to intraoperatively assess the functional integrity of the somatosensorysystem in the spinal cord during surgical correction for scoliosis [2]. The sameSEPs data were also routinely extrapolated to assess the functional integrity ofthe upper motor neuron tracts; however, as data mounted, this approach provedunreliable: (a) it provided false results when SEPs were found to be presentdespite postoperative motor deficits [3, 13] (see Chapter 15, Fig. 15.19, page 386);(b) it provided unreliable (low-quality) or unmonitorable (complete absence) SEPsin patients in whom certain pathologies affected the somatosensory system; and(c) because dorsal myelotomy often destroyed the dorsal column’s integrity inpatients undergoing surgery for intramedullary spinal cord tumors, the abilityto monitor SEPs was immediately nullified [4].

Because of these difficulties, ION was forced to search for more reliable meth-ods to assess the motor system’s functional integrity. Initial attempts to monitormotor tracts in the spinal cord were made in both Japan and the United States.These attempts focused on two neurophysiological techniques: spinal-cord-to-spinal-cord recording, and spinal-cord-to-muscle/peripheral-nerve recording.

1.2 SPINAL CORD TO SPINAL CORD

This technique operates with nonselective electrical stimulation of the spinal cordand with nonselective recordings of elicited potentials from the spinal cord. It isused to record signals from the spinal cord regardless of the direction of prop-agation of the action potentials (either ascending, descending, or ortho/antidromic). The type of action potential recorded depends on the position ofthe stimulating and recording electrodes and the direction of the travelingwaves through the spinal cord with regards to the natural direction of the con-ducting pathways [5].

The evoked potentials recorded from the spinal cord using this technique arethe electrical sum of activity from multiple pathways. Because of the differentconduction properties of the various spinal cord pathways, the recorded poten-tials can show two distinctive wave morphologies. It has been speculated thatone of these waves represents transmission in the dorsal columns (DCs) and theother by the corticospinal tract (CT). Clinical testing on a large number ofpatients with different and relevant pathologies has not been done to confirmthis hypothesis.


28 Vedran Deletis

This method can evaluate the integrity of ascending and descending, and prob-ably propriospinal pathways, within the spinal cord. However, specific informationabout the DC or CT cannot be obtained with this method. Critical reports [6]could not confirm the value of the spinal cord to spinal cord technique in moni-toring motor pathways during surgery for intramedullary spinal cord tumors.

1.3 SPINAL CORD TO PERIPHERAL NERVE (MUSCLE)

This technique operates with nonselective stimulation of the spinal cord and selec-tive recordings from the peripheral nerves or muscles. Recordings from the muscle[7, 8] and peripheral nerves [9] presume that after electrical stimulation of thespinal cord, α-motoneurons are activated only by the CT tract. Therefore, com-pound muscle action potentials (CMAPs) in the limb muscles or electrical activ-ity in the peripheral nerves should be generated by CT stimulation. Unfortunately,α-motoneurons can also be activated by any of the multiple descending tractswithin the spinal cord after diffuse electrical stimulation of the spinal cordand/or by antidromically activated dorsal columns and their segmental branchesthat mediate the H reflex [10]. Electrical activity recorded from mixed periph-eral nerves is a combination of α-motoneuron discharges initiated by the CTand other descending tracts. Because the sensory component of mixed periph-eral nerves is a physical continuation of the dorsal columns, part of the electricalactivity recorded from mixed peripheral nerves after stimulation of the spinalcord arises from the antidromically activated dorsal columns that convey trav-eling waves to the peripheral nerves [10]. Collision studies have challenged thewidely accepted presumption that potentials recorded from peripheral nervesin the lower extremities after stimulation of the spinal cord are generated by theCT [11]. Therefore, there is convincing evidence that selective recording ofthe electrical activity from peripheral nerves elicited by electrical stimulation ofthe spinal cord does not arise from the CT [12]. Additional evidence concern-ing the inaccuracy of monitoring the motor pathways through potentialsrecorded from peripheral nerves is provided in a recent paper by Minahan et al.This paper describes two patients with postoperative paraplegia in spite ofpreservation of these potentials [13].

It is fair to say that both of the techniques described can grossly monitor thefunctional integrity of multiple pathways inside the spinal cord without beingspecific for any of them. In other words, these methods can indicate that cer-tain lesions to the spinal cord have occurred, but they lack the ability to pro-vide specific information as to which of the spinal cord pathways has beendamaged. This methodology may be useful in orthopedic surgical proceduresand other surgeries where lesioning of the nervous tissue within the spinal cordis diffuse in nature and where all pathways are usually affected. An exception to



this phenomenon involves vascular lesions of the spinal cord where selective lesion-ing of the anterolateral columns can occur.

Unfortunately, this nonselective evaluation of multiple pathways is not suf-ficient during surgery of the spinal cord, during which the DCs can be inde-pendently damaged from the anterior and lateral columns [4, 14]. Furthermore,these two techniques (for methodological reasons) cannot evaluate the func-tional integrity of the CT from the motor cortex to the upper cervical spinalcord. Therefore, supratentorial, brainstem, foramen magnum, and upper cervi-cal spinal cord surgeries cannot be monitored using these techniques. This isalso the case in procedures involving the clipping of an intracerebral aneurysm,where the perforating branches for the CT tract in the internal capsula can beselectively damaged while leaving the lemniscal pathways intact. This results ina so-called pure motor hemiplegia (i.e., the patient is postoperatively hemi-plegic while the sensory system is intact and SEPs are present) [10, 15, 16]. Sinceit requires the motor cortex to be surgically exposed, Penfield’s technique maynot be used for monitoring motor tracts within the spinal cord.

2 NEW METHODOLOGIES

Based on previous work by Hill et al. [17], Merton and Morton [18] discoveredthat high-voltage current applied over the skull could penetrate to the brain andactivate the motor cortex and the CT. Although they produced discomfort,these methods of transcranial electrical stimulation (TES) became an additionaltool used to diagnose upper motoneuron lesions in awake patients. On the basisof this work, two methodologies for monitoring the CT intraoperatively weredeveloped, the single-pulse stimulation technique and the multipulse stimula-tion technique.

2.1 SINGLE-PULSE STIMULATION TECHNIQUE

A single-pulse stimulating technique involves a single electrical stimulusapplied transcranially or over the exposed motor cortex while the descendingvolley of the CT is recorded over the spinal cord as a direct wave (D wave).

2.2 MULTIPULSE STIMULATION TECHNIQUE

A multipulse stimulating technique involves a short train of five to seven elec-trical stimuli applied transcranially or over the exposed motor cortex whilemuscle motor-evoked potentials (MEPs) from limb muscles in the form of


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CMAPs are recorded (Fig. 2.1) [28]. (This latter technique differs essentially fromthe Penfield technique in that it calls for only five to seven stimuli with a stimulat-ing rate of up to 2 Hz. Penfield’s technique calls for continuous stimulation over aperiod of a few seconds with a frequency of stimulation of 50–60 Hz, and only inthe cases when the motor cortex is surgically exposed. Furthermore, at such fre-quencies and train durations, seizures are easily induced.)

FIGURE 2.1 (A) Schematic illustration of electrode positions for transcranial electrical stimula-tion of the motor cortex according to the International 10–20 EEG system. The site labeled “6 cm”is 6 cm anterior to CZ. (B) Illustration of grid electrode overlying the motor and sensory cortexes.(C) Schematic diagram of the positions of the catheter electrodes (each with three recording cylin-ders) placed cranial to the tumor (control electrode) and caudal to the tumor to monitor thedescending signal after it passes through the site of surgery (left). In the middle are D and I wavesrecorded rostral and caudal to the tumor site. On the right is depicted the placement of an epiduralelectrode through a flavectomy/flavotomy when the spinal cord is not exposed. (D) Recordingof muscle motor evoked potentials from the thenar and tibialis anterior muscles after being elicitedwith multipulse stimuli applied either transcranially or over the exposed motor cortex. Modifiedfrom [31].



3 METHODOLOGICAL ASPECTS OF TESDURING GENERAL ANESTHESIA

3.1 ELECTRODE MONTAGE OVER THE SCALP

FOR ELICITING MEPS (FOR SINGLE AND MULTIPULSE

STIMULATION TECHNIQUES)

The electrode placement on the skull is based on the international 10–20 EEGsystem (Fig. 2.1A). Note that, instead of CZ, the CZ electrode is placed 1 cmbehind the typical CZ point. Some laboratories have used 2 cm in front of C3or C4 (Z. Rodi, personal communication). For transcranial stimulation, corkscrew–like electrodes (Corkscrew electrodes, Nicolet, Madison, WI) are prefer-able because of their secure placement and low impedance (usually 1 KΩ).Alternatively, an EEG needle electrode may be used. We do not recommendthe use of EEG cup electrodes fixed with collodium since they are impracti-cal and their placement is time-consuming. The only exception is for youngchildren in whom the fontanel still exists. Since the CS electrodes couldpenetrate the fontanel during placement, the use of EEG cup electrodes issuggested.

The skull presents a barrier of high impedance to the electrode currentapplied transcranially; therefore, we cannot completely control the spreadof electrical current when it is applied. For this reason, various combina-tions of electrode montages may need to be explored to obtain an optimal res-ponse. The standard montage is C3/C4 for eliciting MEPs in the upper extrem-ities and C1/C2 for eliciting MEPs in the lower extremities. With sufficientintensity of stimulation at C1/C2, MEPs are preferentially elicited in theright limb muscles while stimulation at C2/C1 elicits MEPs in the left limbmuscles.

With stronger electrical stimulation, the current will penetrate the brainmore deeply, stimulating the CT at a different depth from the motor cortex(Fig. 2.2). On the basis of measurements of the D wave latency, it has been pos-tulated that there are three favorable points that are susceptible to depolariza-tion of the CT: cortex/subcortex (weak electrical stimulation), internal capsula(moderate electrical stimulation), and brainstem/foramen magnum (strongelectrical stimulation). Selectivity of stimulation is possible at the level of thecortex (subcortex). Therefore, only the application of relatively weak electricalstimuli to the cortex is selective, and it activates only a small portion of the CTfibers (e.g., activating only one extremity) or only one CT. It is important toremember that during electrical stimulation of the motor cortex, the anode ispreferentially the stimulating electrode. With increasing intensity of the current,the cathode becomes the stimulating electrode as well.


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As an example, stimulation with the C3+/C4− will selectively activate mus-cles of the right arm. When stimulation intensity is increased, the cathode(C4−) becomes the stimulating electrode as well, resulting in the stimulationof the left arm. Finally, when current intensity becomes strong enough to pen-etrate to the internal capsule more caudally, all four extremity muscles can beactivated. For anatomical reasons (deep position of the leg motor area in theinterhemispheric fissure), more intense current is usually needed to obtainMEPs in the lower extremities. It is especially difficult to obtain them sepa-rately without also activating the upper extremities. Our observation has beenthat it can be done in certain patients, especially when using the CZ/6 cm infront montage (see Fig. 2.1).

By their anatomical location, recording electrodes in the limb muscles canindicate which fibers of the CT are activated predominantly (left or right,fibers for upper or lower extremities). If one would like to activate left andright CT simultaneously to obtain D wave recordings, weak electrical stimu-lation should be avoided and a moderate intensity should be used. In Fig. 2.3,it is obvious that weak electrical stimulation activates fibers of the CT for theleft upper extremities only. This can result in activation of only one CT whilenot affecting the other CT. Therefore, the intensity of electrical stimulationfor eliciting a D wave should be determined by simultaneous recordings ofMEPs from limb muscles (indicating which fibers of the CT have been pre-dominantly activated), or only moderate intensities of electrical current foreliciting D waves should be used. The moderate intensity of electrical current

FIGURE 2.2 D and I waves recorded after a single electrical stimulus delivered transcranially (CZanode/6 cm anterior cathode) in 14-year-old patient with idiopathic scoliosis. When the intensityof the stimulus is increased, electrical current activates the CT deeper within the brain and thelatency of the D wave becomes shorter. As current becomes stronger, more I waves are induced(100% corresponds to 750 volts of stimulator output). Modified from [10].



will activate both CTs at the level of the internal capsule. If MEP waves havenot been simultaneously recorded with D waves, the following guidelinesshould be followed: increase the intensity of the stimulation until D waves donot increase in amplitude (Fig. 2.2, the third trace from the top). This is a signthat most of the fast conducting neurons of CT from the left and right CT havebeen activated.

The neurophysiological mechanism for eliciting MEPs by stimulating themotor cortex in patients under the influence of anesthetics is different fromthe mechanism in the awake subject. In the latter, electrical current stimulates thebody of the motor neuron transynaptically over the chain of vertically orientedexcitatory neurons, resulting in I waves (indirect activation of the motoneu-rons). At the same time, electrical current activates axons of the corticalmotoneurons, directly generating D waves [19]. In anesthetized patients, anes-thetics block the synapses of the vertically oriented excitatory chains of neuronsterminating on the cortical motoneuron’s body. Therefore, only the D wave isgenerated after electrical stimulation of the motor cortex [19, 20]. Patients withidiopathic scoliosis are an exception. In this group, abundant I waves can berecorded (Fig. 2.2). We believe that this is one of the neurogenic markers of thedisease present in these patients [21]. Furthermore, it has been shown that afrontally oriented cathode preferentially generates I waves because at this stim-ulating setting corticocortical projections of vertically oriented interneuronsare optimally activated. With the cathode in the lateral position, this is not thecase [22, 23] (Fig. 2.4).

FIGURE 2.3 Transcranial electrical stimulation over the C4 anode/C3 cathode with recordingsof the D wave over the C6–C7 segment (above) and the T7–T8 segment of the spinal cord (below).Stimulus intensity was 35 and 40 mA, respectively. Stronger stimuli elicit the D wave over the tho-racic spinal cord, while a weaker stimulus (35 mA) elicits the D wave only over the cervical spinalcord.


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4 RECORDING OF MEPs OVER THE SPINAL CORD(EPIDURAL AND SUBDURAL SPACES) USINGSINGLE-PULSE STIMULATION TECHNIQUE

4.1 D WAVE RECORDING TECHNIQUE THROUGH AN

EPIDURALLY OR SUBDURALLY INSERTED ELECTRODE

This method is a direct clinical application of Patton and Amassian’s [19] dis-covery in the 1950s that electrically stimulated motor cortex in monkeys gen-erates a series of well-synchronized descending volleys in the pyramidal tract.This knowledge of CT neurophysiology, which was collected in primates, canbe applied to humans in most cases.

We have to be aware that even small methodological aspects of recording Dwaves are of the utmost importance and should be followed in order to achievereliable results.

4.1.1 Choice of Electrode

Practically any type of catheter-type electrode designed for electrical stimulationof the spinal cord epidurally can be used for recording D and I waves. We preferto use the JX-300 (Arrow International, Reading, PA) because of its optimalrecording properties and intercontact recording electrode distance (Fig. 2.5). Thiselectrode has three platinum-iridium recording cylinders 3 mm in length, 1.3 mmin diameter, and 18 mm apart, with recording surfaces of approximately 12.3 mm2.

FIGURE 2.4 Upper thoracic epidural recordings of D and I waves in a 14-year-old female duringsurgery for a low cervical intramedullary tumor. The upper trace was obtained after transcranialelectrical stimulation over C1 (anode) and C2 (cathode) using 140 mA stimulus intensity and astimulus duration of 500 µs. The lower trace was obtained after anodic stimulation at CZ and catho-dal stimulation at 6 cm anterior to CZ, using the same stimulus duration but at 200 mA. Note theappearance of the D and I waves with this electrode arrangement. (An upward deflection is nega-tive.) Reprinted from [23].



This electrode is semi-rigid, a property that facilitates its placement either per-cutaneously or through flavotomy. Furthermore, it consists of a double lumenwith two openings at the tip of the electrode. This allows for the injection ofsaline to flush the recording contact surfaces and reduce impedance. This is animportant methodological detail in the case of bad electrode contact if the elec-trode is placed percutaneously in the epidural space (where it can face a highimpedance). Once the electrode is in place, it is very difficult to reposition it.Thus an injection of saline through the outer lumen is a method of rectifyingthe high-impedance problem (Fig. 2.6). When the electrode is placed afterlaminectomy, problems with impedance and positioning of the electrode areeasier to solve because the surgeons are able to reposition the lead.

Most epidural electrodes are disposable. If one uses a nondisposable type,extreme care should be taken to ensure that the electrode is clean before steril-ization and thus has improved electrical properties. To clean the electrode, werecommend one of the following procedures. You can immerse the electrode tipin saline and pass a 9 V DC current (regardless of polarity) through it until abubble of gas cleans the contact surface for a period of a few minutes, or youcan use an ultrasound cleaner (Branson 1210, Branson Ultrasonics Corpora-tion, Danbury, CT) by submersing the electrode in the cleaner for 5 minutes.

FIGURE 2.5 Semi-rigid catheter electrode for recording MEPs (D wave) from the spinal cord, epi-or subdurally. The electrode has passed through a 14-gauge Touhy needle for percutaneous place-ment epidurally. To the left (enlarged) are two openings marked with asterisks for flushing the threecylindrical recording contacts (1, 2, 3) through the injection site (top, right).


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Both techniques will remove any film or biological material remaining on theelectrode from the contact surfaces and will decrease their impedance. Thismaneuver will diminish the stimulus artifact, which usually appears when con-tact surfaces have high impedance. Because of the short latency of the D wave,a large stimulus artifact in an uncleaned electrode can pose an insurmountableobstacle for D wave recording.

4.2 PROPER PLACEMENT OF EPIDURAL ELECTRODES

Depending on the surgical procedure, there are two methods of electrode place-ment: percutaneously, or after laminectomy/laminotomy or flavotomy/flavectomy.

4.2.1 Percutaneous Placement of Catheter Electrode

This technique is rather popular in Japan [5]. As used there, it is slightly differ-ent from the one we employ, since the neurosurgeon may ask for a subduralplacement of the catheter electrode. We have performed this procedure to mon-itor the CT during brainstem and supratentorial surgeries where there is high riskof potential damage. Today, because of the increasing popularity of MEPs moni-toring during procedures involving the spinal cord and brainstem, the demand(indications) for percutaneous placement of this type of electrode has dimin-ished. When we do use percutaneous placement, a 14-gauge, thin-wall Touhyneedle (T466LNRH, Becton Dickinson and Comp, Franklin Lakes, NJ; Fig. 2.5),is used for introducing the electrode into the epidural space percutaneously. Fol-lowing percutaneous electrode placement, care must be taken not to withdraw theelectrode while the Touhy needle is in place. Otherwise, the sharp edge of the

FIGURE 2.6 Two traces with a D wave recorded epidurally at the lower cervical spinal cord afterpercutaneous placement of the epidural electrode in a patient with a brain tumor. High impedanceresults in a large artifact (lower trace) which has been reduced (upper trace) after injection of salineinto the epidural space (see Fig. 2.5).



needle could shred the wall of the electrode. The optimal position for penetrat-ing the epidural space with the Touhy needle is the upper thoracic (T1–T2)epidural space. With the needle in this region, the catheter electrode can be gentlypushed up to the level of the lower cervical spinal cord. With this electrode place-ment we can monitor the CT for both the upper and lower extremities by record-ing D waves after selective stimulation of the motor cortex. Appropriate electrodeplacement can be confirmed either by x-ray or by recording epidural SEPs fromthe same electrode after stimulation of the median or ulnar nerves.

In two series consisting of 57 patients [24] and 16 patients [25], no compli-cations from the placement of the electrode occurred (e.g., bleeding, infection,or puncture of the spinal cord). This method requires skills that the anesthesi-ologist practiced in the epidural injection of anesthetics would typically have.

4.2.2 Placement of Electrode after Laminectomy/Laminotomyor Flavectomy/Flavotomy

Our center uses this technique regularly for all procedures that require CT mon-itoring when a laminectomy is performed. These procedures include surgery forthe removal of spinal cord tumors and different surgical interventions on thespinal cord. The surgeon places two catheter electrodes in the epi- or subduralspace at the rostral and caudal edge of the laminectomy. The rostral electrode isthe control electrode for nonsurgically induced changes in the D wave, while thecaudal one monitors the surgically induced changes to the CT (see Fig. 2.1).Massive dural adhesions, usually from previous surgery or after spinal cord radi-ation, can prevent the placement of the catheter electrode. Also, placementbelow the T10 bony level cannot record a D wave of sufficient amplitude becauseof lack of sufficient CT fibers. The control (rostral) electrode cannot be placedin cases of high cervical spinal cord pathology because of the lack of space. Theamplitude of the D wave recorded over the cervical spinal cord could be 60 µVor more, while over thoracic segments it may be only 10 µV. With a stimulatingrate of 2 Hz, it takes two to four averaged responses to get a reliable D wave. Thisresults in an update every second. Unfortunately, the maximal stimulating ratefrom commercially available TES stimulators is 1 stimulus per second.

In surgical procedures in which the spine is exposed but a laminectomy is notperformed (e.g., surgical corrections of scoliosis or dorsal approach to spine stabi-lization), the catheter electrode may be inserted through a flavotomy/flavectomy.

4.3 FACTORS INFLUENCING D AND I WAVE RECORDINGS

D waves represent a neurogram of the CT which is not significantly influencedby nonsurgically induced factors. Stimulation of the CT takes place intracraniallydistal to the cortical motoneuron body, while recording is done caudal to the


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surgical site but above the synapses of the CT at the α-motoneuron. Since nosynapses are involved between the stimulating site and the recording site, theD wave is very stable and reliable. Therefore, we consider D wave recordings tobe the “gold standard” for measuring the functional integrity of the CT.

Still, there exists a few nonsurgically induced changes that will affect the Dwave. Being able to correctly recognize them is essential to giving the surgeonappropriate information. If the exposed spinal cord is cooled, either by cold irri-gation with saline or low operating room temperature, the latency of the Dwave will be temporarily prolonged (Fig. 2.7). Sometimes during stimulation,even with a single stimulus, the epidural electrode can pick up the paraspinalmuscle artifact. This would affect the I wave, but not the D wave, parameters(see Fig. 2.8). If this phenomenon occurs, it is more frequent during cervicalthan thoracolumbar catheter placement.

In contrast to those of others [26], our data demonstrate that volatile anes-thetics do not change the parameters of the D wave by influence on the mem-brane properties of the CT. To demonstrate this, we see that as isofluraneconcentration increases (e.g., >2%), the latency of the D wave gets prolongedwhile the amplitude diminishes (see Fig. 2.9). However, this can be easily cor-rected by increasing the intensity of the current. Therefore, we believe that themechanism by which isoflurane influences the parameters of the D wave isvasodilatation of the cortical blood vessels. Because of the vasodilatation, cur-rent between the stimulating electrodes shunts and activates the CT moresuperficially, resulting in longer latencies of the D wave. The smaller amplitudeof the D wave results from fewer fibers of the CT being activated if current flowssuperficially (Fig. 2.10). A prolongation of the latency and a diminished ampli-tude of the D wave occur only if the CT is activated transcranially. In contrast,this phenomenon is not present when the motor cortex is stimulated directly

FIGURE 2.7 D waves recorded over the lower cervical spinal cord in a patient with an upper cer-vical intramedullary spinal cord tumor, after stimulation with CZ anode/6 cm anterior cathode.Temporary cooling of the exposed spinal cord results in delayed latency of the D and I waves. Afterwarming of the spinal cord, the latency of the D and I waves returned to the previous values.Reprinted from [10].



FIGURE 2.8 Epidurally recorded D and I waves over the cervical spinal cord showing a muscleartifact. After administration of the muscle relaxant, the muscle artifact disappears. The muscle arti-fact affects the I wave, but not the D wave, recordings. S = beginning of transcranially applied stim-ulus. Modified from [10].

FIGURE 2.9 Transcranial electrical stimulation (CZ anode/6 cm anterior cathode) and directelectrical stimulation of the exposed motor leg area with recording of the D wave over the lowerthoracic spinal cord in two different patients. Identical concentrations of isoflurane showed aprominent effect on the amplitude and latency of the D wave (50% decrement of amplitude and0.5 ms prolonged latency after end tidal concentration of 2% isoflurane). This effect is only evidentwhen transcranial electrical stimulation is used. A minimal effect of isoflurane on D wave parame-ters was observed when electrical stimulation was applied to the exposed cortex. Reprinted from [10]and [34].


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through a grid electrode with a short distance between the electrodes. All of theabove observations provide evidence that changes in the D wave are due tomechanisms other than influence on the CT axon membranes.

4.4 NEUROPHYSIOLOGICAL MECHANISMS LEADING

TO THE DESYNCHRONIZATION OF THE D WAVE

In certain patients with spinal cord tumors (usually involving a few segments)the D wave is not recordable at the beginning of surgery [27]. At the same time,muscle MEPs are recordable, even in patients that may not necessarily have amajor motor deficit (Fig. 2.11). The temporal summation of the desynchro-nized D waves occurs at the segmental level. The same phenomenon is presentin patients who undergo radiation of the spinal cord. We believe this is a resultof a desynchronization in conduction of the CT axon. In other words, fast fibersof the CT conduct D waves with different speeds over the site of the lesion orirradiation. Therefore, desynchronized D waves cannot be easily demonstratedcaudal to the lesion site with the present methodology. There are differentgrades of desynchronization, which will be seen as low-amplitude and wide-base D waves (Fig. 2.11A). A higher degree of desynchronization is representedby a nonrecordable D wave (Fig. 2.11B).

Patients who do not have a recordable D wave at the beginning of surgeryare challenging for the monitoring team because they represent a high-riskgroup of patients for injury to the CT. With the present methodology, we canonly monitor them by recording MEPs from limb muscles. Because of the

FIGURE 2.10 To the left, current flow is represented schematically before (white line) and after(grey line) administration of isoflurane. Because of the vasodilatatory effects of isoflurane on thecortical blood vessels, the current between the two stimulating electrodes is shunted, flowingthrough the brain more superficially. This results in a prolonged latency and smaller amplitude ofthe D wave when compared to a D wave elicited with the same intensity of current without isoflu-rane (6.0 ms vs. 6.3 ms, respectively; to the right). At the same time, the disappearance of the I wavecan be observed under the influence of isoflurane.



possibility that transient paraplegia may occur, this is not an ideal monitoringtool. When muscle MEPs disappear during surgery in the patients who do nothave a recordable D wave at baseline, it is not possible to distinguish transientfrom permanent motor deficit intraoperatively (see Section 5.3).

5 RECORDING OF MEPs IN LIMB MUSCLESELICITED BY A MULTIPULSESTIMULATING TECHNIQUE

5.1 SELECTION OF OPTIMAL MUSCLES IN UPPER

AND LOWER EXTREMITIES FOR MEP RECORDINGS

The selection of appropriate muscles to record from is an important issue in themonitoring of MEPs. In certain patients who have deep paresis, not choosingthe optimal muscles can result in “nonmonitorable” patients. The small handmuscle (e.g., abductor pollicis brevis, or APB) is one of the optimal muscles to

FIGURE 2.11 (A) Recording of a D wave cranially (upper trace) and caudally (lower trace) to theintramedullary spinal cord tumor. Note the well-synchronized D wave cranially, in contrast to thedesynchronized D wave caudal to the tumor. (B) Very small epidurally recorded MEPs caudal to ahigh cervical intramedullary tumor (due to extreme desynchronization), despite large muscle MEPsrecorded from a small hand muscle elicited after a short train of six stimuli were present (to theright). Modified from [33].


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monitor the CT for the upper extremities. It has been shown that a good alter-native is the long forearm flexors [28], or even the forearm extensors. Thespinal motoneurons for these muscle groups have rich CT innervation and aretherefore suitable for monitoring the functional integrity of the CT. This is notthe case with the proximal muscle of the arm or of the shoulder (biceps, triceps,or deltoid muscles).

For the lower extremities, abductor hallucis brevis (AHB) is the optimalmuscle because of its dominant CT innervation. In animal experiments, it hasbeen shown that after CT stimulation the highest amplitude of the excitatorypostsynaptic potential (EPSP) has been found in the α-motoneuron pools forthe lower extremities in the small and long flexors of the foot [29]. An alterna-tive to this muscle is the tibialis anterior muscle (TA). Our standard electrodemontage for recording MEPs in the upper and lower extremities are the AHBand TA for the lower extremities and the ABP for the upper extremities.

5.2 NEUROPHYSIOLOGICAL MECHANISMS

FOR ELICITING MEPS USING A MULTIPULSE

STIMULATION TECHNIQUE

Understanding the mechanism involved in the generation of MEPs is essentialfor describing their appropriate use, explaining their behavior, understandingtheir value, and knowing their limits during the monitoring of the CT. Gener-ation of MEPs is more complex in nature than the generation of the D and Iwaves. Therefore, their interpretation, especially during anesthesia, is rathercomplex. Generation of MEPs and their propagation to the end organ (muscle)depends on (a) the excitability of the motor cortex and the CT tract, (b) theconductivity of CT axons, (c) the excitability level of α-motoneuron pools,(d) the role played by the supportive system of the spinal cord (helping toincrease the excitability of α-motoneurons), and (e) the integrity of motornerves, the motor endplates and muscles.

5.2.1 Recovery of Amplitude and Latency of the D Wave

There is a frequency limit for the transmission of descending volleys throughthe CT axons to the α-motoneurons. This limit can be easily tested by apply-ing two identical electrical stimuli transcranially with different interstimulus inter-vals (ISIs). This test can show the recovery time of the second D wave response.



Using this paradigm (conditioning and test stimuli), a D wave recovery curvecan be plotted relative to the amplitude and latency of the second D wave (Fig.2.12). In a paper recently published [30], we show that the optimal ISI for com-plete recovery of the second D wave amplitude and latency is around 4 ms,using a moderate stimulus intensity with a duration of 500 µs. Because the α-motoneuron is optimally bombarded when the train of equal stimuli elicits Dwaves of equal amplitudes, the optimal ISI for muscle activation is expected tobe 4 ms. Fig. 2.13 indicates that with an ISI of 4 ms, three stimuli are sufficientto elicit MEPs because of the complete recovery of each consecutive D wave(Fig. 2.13B3). Comparatively, using the identical stimulus intensity but decreas-ing the ISI to 2 ms, five stimuli are needed to elicit MEPs, which are of even smalleramplitude, because of incomplete recovery of the amplitude of each consecu-tive D wave (Fig. 2.13A5). This rule applies only if a single stimulus elicits asingle D wave (see Section 5.2.3).

FIGURE 2.12 Two diagrams showing the relationship between interstimulus interval (ISI), dura-tion of stimuli, and recovery of the amplitude and latency of the conditioning D wave. Two iden-tical stimuli have been applied transcranially with different ISIs. Amplitude and latency of thesecond D wave (D2) were compared to those of the first one (D1). Note that earlier and completerecovery of the amplitude and latency of the second D wave occurs with a stimulus duration of 500 µsand an ISI of around 4 ms. Reprinted from [30].


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5.2.2 Facilitation of I Wave

We have been shown that three stimuli applied transcranially over the motorcortex can elicit more than three descending volleys in lightly anesthetizedpatients [31]. In Fig. 2.13A3, it is clearly visible that three stimuli generate fourdescending volleys (D1, D2, D3, and an additional I wave). Facilitation of pre-viously nonexisting I waves (after a single stimulus, Fig. 2.13A1) is one of theimportant factors underlying the potency of the multipulse stimulating tech-nique for eliciting MEPs in lightly anesthetized patients. Furthermore, it hasbeen shown that because of the lack of synchronicity of I waves, their recordedamplitude is only one third of their actual amplitude [32]. Certainly, if thepatient is deeply anesthetized, the cortical synapses where the I wave was facil-itated are completely blocked, so this phenomenon does not occur.

5.2.3 Total Number of D and I Waves

As stated previously, to allow for the complete recovery of the D wave, the ISIin the multipulse train should be 4 ms. In situations where a single stimulusgenerates more than a single D wave, the optimal ISI should be set long enoughto allow the entire set of D and I waves to recover, and in turn, to allow the next

FIGURE 2.13 Relationship between MEPs recorded epidurally and from muscle. (A) Train of fivestimuli are needed with an ISI of 2 ms in order to elicit muscle MEPs in tibialis anterior muscle (A5).(B) With an ISI of 4 ms, only three stimuli are needed to elicit muscle MEPs in the tibialis anteriormuscle (B3). D = D wave; I = I wave; PM = paraspinal muscle artifact. Reprinted from [31].



set of D and I waves to fully develop. Therefore, the second stimulus can gen-erate the same pattern of D and I waves (Fig. 2.14). Otherwise, the second setof D and I waves could fall into the CT axon refractory period resulting fromthe first set. This is the case in Fig. 2.14, where a single stimulus generates asingle D wave and multiple I waves (A). In this case only two stimuli, 8 ms apart,were necessary to generate the maximum amplitude of muscle MEPs (Fig. 2.14D).If the ISI is shorter (e.g., 4.1 ms in Fig. 2.14B), partial cancellation of the D andI waves elicited by a second stimulus will occur. Consequently, the total numberof D and I waves will be insufficient to bring an α-motoneuron to the firing leveland MEPs will not be generated. This mechanism could be important in thelightly anesthetized patient as well as in patients with idiopathic scoliosis wherea single stimulus generates multiple I waves (see Fig. 2.2).

5.2.4 Generation of Muscle MEPs Depends on Two Systems:The CT and the Supportive System of the Spinal Cord

To reiterate, descending activity from the CT axons alone is not sufficient togenerate muscle MEPs in anesthetized patients. The other system(s) should beactivated as well. Three examples support this statement:

FIGURE 2.14 (A) In this patient, a single stimulus delivered over the exposed motor hand area elic-its a single D wave and multiple I waves. The ISI should be long enough to prevent the second set ofD and I waves, elicited by a second stimulus, from falling into the CT axon refractory period result-ing from the previous waves (as is the case in trace B). When the ISI is 5.9 ms (C) and 8.0 ms (D),this will not occur, resulting in a sufficient numbers of D and I waves to elicit MEPs (trace D). Thestimulus is marked by an arrow and the D wave by an asterisk. Reprinted from [31].


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A. If the multipulse technique (in a non-deeply anesthetized patient) with arepetition rate of 1 or 2 trains per second is performed, each consecutiveresponse recorded from muscle will have an increasing amplitude. In caseswhere the intensity of stimuli is just slightly above the threshold, the first fewtrains will not generate muscle MEPs at all. At the same time, the D wave ampli-tudes remain the same (Fig. 2.15).

B. In the patients with intramedullary spinal cord tumors presented in Fig.2.16, recording of the D waves from the left and right CT generates symmet-rical D waves cranially and caudally to the tumor site. Yet muscle MEPs are sig-nificantly smaller over the right TA muscle where the patient has clinicalweakness. The presumption is that the current required to elicit MEPs frommuscles on one side of the body is activating only one CT. Therefore, the Dwave, recorded from the spinal cord using this same intensity, must predom-inantly belong to one CT.

C. During surgery for intramedullary spinal cord tumors, muscle MEPs cancompletely disappear with no significant changes in the amplitude of the Dwave (see further transient paraplegia, Fig. 2.17).

These three examples provide convincing evidence that the generation of MEPsinvolves more than just the CT system (see Section 5.3.1).

FIGURE 2.15 Recordings of 10 consecutive muscle MEPs from the right abductor hallucis brevismuscle (after delivering 10 trains consisting of five stimuli, pulse width of 100 µs, intensity of288 mA, stimulus rate of 1 Hz) over C3 anode/C4 cathode in a 60-year-old patient undergoing ante-rior cervical spine decompression and stabilization. Note that after the fifth train the amplitude ofthe muscle MEPs increases 10-fold, showing a tendency to further increase its amplitude.



FIGURE 2.16 Simultaneous recording of the D wave from the right and left CT, cranial and caudalto a midthoracic intramedullary spinal cord tumor (upper), showing a symmetrical amplitude of theD wave. At the same time, muscle MEPs showed significantly smaller amplitude over the right TAmuscle when compared to the left, correlating with the patient’s weakness in the right leg. Thisrecording indicates involvement of pathways other than the CT in the generation of the MEPs.

FIGURE 2.17 Muscle MEPs recorded from right and left TA muscle (left) and D wave recordedepidurally over the lower cervical spinal cord (right). During surgery, muscle MEPs completely dis-appeared while the D wave decreased in amplitude (less than 50%), resulting in transient paraple-gia for this patient during surgery for an intramedullary spinal cord tumor. The patient recoveredcompletely within a week. Reprinted from [33].


48 Vedran Deletis

5.3 SURGICALLY INDUCED TRANSIENT PARAPLEGIA

During surgery for intramedullary spinal cord tumors in the thoracic region,MEPs in the TA muscles will frequently disappear while the D wave remainsunaffected. All patients demonstrating this finding during surgery wake upparaplegic (or monoplegic if the TA MEPs disappear in one leg). In patientsin whom we have observed this phenomenon, motor strength is typicallyrecovered in a few hours to a few days following surgery. No permanentmotor deficits have been observed [14, 33] (Fig. 2.17). With almost all casesof transient paraplegia, the first changes are seen in the MEPs and not in theparameters of the D wave. This gives the surgeon a warning sign and awindow of time to plan to end the tumor removal. This is a critical point forintraoperative planning of the extent of tumor removal. If changes in theMEPs do not appear, tumor removal can proceed until a gross total resec-tion is accomplished without the patients having permanent motor deficitspostoperatively.

5.3.1 Neurophysiological Basis for Surgically InducedTransient Paraplegia

Taking into account the previous evidence that the generation of muscle MEPsinvolves more than just the CT, activation of the CT and other descendingsystems within the spinal cord is necessary. We speculate that the pro-priospinal (diffuse) system of the spinal cord is activated by CT axons that arelinked via synaptic connections to the propriospinal system within the spinalcord. In the case of surgically induced transient paraplegia, this system istemporarily compromised by selective surgery while the CT is left intact.After the patient wakes up, other descending systems compensate for the lackof propriospinal tonic influence on α-motoneurons. This results in the fastrecovery of these patients. This suggested mechanism is speculative but froma prognostic and pragmatic point of view is critical because it correlatesextremely well with clinical outcome. Comparatively, if the CT tract is dam-aged during surgery (complete loss of D wave or decrement of the amplitudecompared with the baseline of more than 50%), a permanent motor deficit isexpected [27].

Combining the information about the D wave and about the muscle MEPsduring surgery for intramedullary spinal cord tumors makes this surgery safer,changes the intraoperative strategy, and significantly diminishes the occurrenceof postoperative deficits (see Chapter 4).



6 CONCLUSION

Historically, intraoperative neurophysiology has progressed by means of trialand error. Unfortunately, this has resulted in a number of different opinions asto its utility in documenting and preventing surgically induced neurologicalinjury. In spite of this, the methodology for monitoring the functional integrityof the CT has progressed over the last 10 years into a reliable, fast, and relativelysimple tool that is easily utilized intraoperatively. The development of such asolid methodology has given us reliable and specific data that highly correlatewith neurological outcome postoperatively. This correlation and the publishedsurgical outcome data demonstrate the merits of these techniques.

Further developments in intraoperative neurophysiology should be directedtoward developing a methodology for the functional mapping of the nervoustissue in the exposed brain, brainstem, and spinal cord during surgery. Thefirst steps in this direction have given promising results (see mapping of thedorsal columns, Chapter 7), brainstem cranial motor nuclei (see Chapter 14),and mapping of pudendal afferents (see Chapter 9). We have recently reportedthe first trials using a technique for mapping the CT intraoperatively [35], andwe hope that this technique will evolve into a method for identifying the CTduring exposed brain and spinal cord surgery. Included with the accompany-ing CD is a video showing epidurally recorded D waves and muscle MEPsrecorded from limb muscles during surgery for the removal of an intramed-ullary tumor.

A CD-ROM video presentation will depict actual operating room imple-mentations of these methods (choose Chapter 2 from the accompanying CD’smain menu).

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13. Minahan, R.E., Sepkuty, J.P., Lesser, R.P., Sponseller, P.D., and Kostuik, J.P. (2001). Anteriorspinal cord injury with preserved neurogenic “motor” evoked potentials. Clin. Neurophysiol.,112, 1442–1450.

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17. Hill, D.K., McDonnell, M.J., and Merton, P.A. (1980). Direct stimulation of the abductor pol-licis in man. J. Physiol., 300, 2P.

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21. Deletis, V., Kiprovski, K., Neuwirth, M., and Engler, G. (1994). Do neurogenic lesions of thespinal cord generate distinctive features of the epidurally recorded motor evoked potentials?In “Handbook of spinal cord monitoring” (S.J. Jones, S.M. Boyd, and N.J. Smith, eds.), pp.266–271. Kluwer Academic Publishers, Dordrecht.

22. Kaneko, K., Kawai, S., Fuchigami, Y., Morieta, H., and Ofuji, A. (1966). The effect of currentdirection induced by transcranial magnetic stimulation on the corticospinal excitability inhuman brain. EEG Clin. Neurophysiol., 101, 478–482.

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24. Canter, M., and Deletis, V. (1995). Spinal epidural electrode catheter for intraoperative record-ing of evoked potentials (EPs) and injection of drugs. Sixth International Symposium on SpinalCord Monitoring, abstract book, pp. 50, New York, June 1995.

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26. Burke, D., Barthley, K., Woodforth, I.J., Yakoubi, A., and Stephen, P.H. (2000). The effects ofa volatile anesthetic on the excitability of human corticospinal axons. Brain, 123, 992–1000.

27. Morota, N., Deletis, V., Shlomi, C., Kofler, M., Cohen, H., and Epstein, F. (1997). The role ofmotor evoked potentials (MEPs) during surgery of intramedullary spinal cord tumors. Neuro-surgery, 41, 1327–1366.

28. Taniguchi, M., Cedzich, C., and Schramm, J. (1993). Modification of cortical stimulation formotor evoked potentials under general anesthesia: Technical description. Neurosurgery, 32(2),219–226.

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31. Deletis, V., Rodi, Z., and Amassian, V. (2001). Neurophysiological mechanisms underlyingmotor evoked potentials (MEPs) elicited by a train of electrical stimuli: Part 2. Relationshipbetween epidurally and muscle recorded MEPs in man. Clin. Neurophysiol., 112, 445–452.

32. Amassian, V.E., and Deletis, V. (1999). Relationships between animal and human corticospinalresponses. In “Transcranial magnetic stimulation” (W. Paulus, M. Hallett, P.M. Rossini, andJ.C. Rothwell, eds.), pp. 79–92. Elsevier, New York. Electroencephalogr. Clin. Neurophysiol.suppl. 51.

33. Deletis, V., and Kothbauer, K. (1998). Intraoperative neurophysiology of the corticospinaltract. In “Spinal cord monitoring” (E. Stalberg, H.S. Sharma, and Y. Olsson, eds.), pp. 421–444.Springer, Wien, New York.

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C H A P T E R 3

Spinal Cord Surgery GEORGE I. JALLO AND FRED J. EPSTEIN

Hyman-Newman Institute for Neurology and Neurosurgery,Beth Israel Medical Center, New York

1 Introduction2 Epidemiology and Histology3 Clinical Presentation4 Diagnostic Studies5 Surgical Management

5.1 Surgical Instruments5.2 Surgical Techniques

6 Outcome Following Surgery7 Surgical Complications

7.1 Deterioration in Functional Outcome7.2 Cerebrospinal Fluid Leak


ABSTRACT

This chapter reviews the current surgical management for intramedullary neo-plasms. The optimal management of these neoplasms remains controversial. Themajority of these tumors are histologically benign, with low-grade astrocytomasbeing the most common in children, whereas ependymomas are the most commonhistology in adults. These tumors typically have a long prodrome of symptoms thatinclude pain, motor deficit, or sensory loss. The recommended surgical approachis an osteoplastic laminotomy or laminectomy and radical resection of the tumor.This surgery is supplemented by specialized instruments such as the contact laserand ultrasonic aspirator as well as intraoperative neurophysiology. Gross totalresection is feasible for ependymomas, hemangioblastomas, and cavernomas andresults in a surgical cure. Although astrocytomas are typically infiltrative neo-plasms, the radical resection with intraoperative neurophysiology results in a longprogression-free survival. We avoid adjuvant radiotherapy for all neoplasms exceptthe rare malignant glioma. These high-grade tumors have a dismal outcome, andsurgery in these patients should be a conservative debulking with preservation ofneurological function.


Deletis_Quark_C03.qxd 6/13/02 12:51 PM Page 55

1 INTRODUCTION

The first successful resection of an intradural tumor, a fibromyxoma, wasaccomplished in 1887 by Victor Horsley [1], and the first successful resectionof an intramedullary spinal cord tumor was performed in 1907 by Anton vonEiselberg [2] in Austria. However, the first report of an intramedullary tumorwas written in 1911 by Charles Elsberg in New York [3]. Elsberg described atwo-stage strategy for the removal of these intramedullary tumors. At the ini-tial operation a myelotomy would be performed. The surgeon would thenreturn one week later to remove the spinal cord tumor. This technique allowedthe neurosurgeon to remove only the extruded portion of an intramedullarytumor. Tumor within the spinal cord would not be removed for fear of neuro-logical injury.

Following these initial reports for spinal cord tumors, other pioneering neuro-surgeons attempted spinal cord surgery. However, the complication rate, whichincluded surgery at wrong levels, cerebrospinal fluid leaks, infection, paralysis,and death, was quite significant. Thereafter, many neurosurgeons recom-mended a conservative approach with biopsy, dural grafting, and radiation ther-apy regardless of histological diagnosis [4]. With the advent of the operatingmicroscope, development of microsurgical techniques, imaging technology,and intraoperative neurophysiology, the strategy for these intramedullary neo-plasms has further evolved. The majority of spinal cord tumors are histologi-cally benign [5, 6], and the radical or gross total removal results in long-termsurvival with an acceptable morbidity [6–11].

2 EPIDEMIOLOGY AND HISTOLOGY

Tumors of the intramedullary spine account for only 5 to 10% of all central ner-vous system tumors. A review of the computer surgical pathology database forintramedullary lesions at a single institution between 1991 to 1998 yielded 294cases in adults and children [5]. The majority of these tumors were operatedupon by the senior author (FJE). The 294 tumors included 117 removed fromchildren under the age of 21 years, and 177 from patients 21 years and older(Table 3.1). The most common single tumor type in children was the fibrillaryastrocytoma, which accounted for 45 (39%) of the tumors. There were 31gangliogliomas, which were almost as common as the low-grade fibrillaryastrocytoma in the pediatric population. In our study of 164 children withintramedullary neoplasms, the majority of the tumors were located in the cer-vicothoracic or thoracic spinal cord (Fig. 3.1) [6]. In contrast, ependymomasare the predominant tumor in adults, accounting for 45% of 177 intramedullarytumors [5].

56 George I. Jallo and Fred J. Epstein


3 CLINICAL PRESENTATION

Intramedullary tumors may remain asymptomatic for a long time or cause non-specific complaints that make the diagnosis difficult. The most common symp-tom of an intramedullary tumor in adults is pain. The pain may be diffuse orradicular in nature. There is no characteristic feature of the pain distribution inpatients with intramedullary tumors, but patients with an intramedullaryependymoma tend to have dysesthetic pain as compared to astrocytomas. Thediagnosis is even more difficult in children, who may not complain of pain,dysesthesias, or sensory loss. Other children may only complain of symptomsfollowing a trivial fall or accident. Younger infants may even present with

Spinal Cord Surgery 57

TABLE 3.1 Histological Diagnoses of Intramedullary Neoplasms at a Single Institution between 1991–1998

Tumor type Children Adults

Juvenile Pilocytic Astrocytoma 4 4

Fibrillary Astrocytomas 45 44Low Grade 32 22Anaplastic 10 21Glioblastoma 3 1

Ependymomas 14 74Myxopapillary 5 14Subependymoma 0 5

Oligodendroglioma 1 0

Mixed Glioma 3 5

Ganglioglioma 31 10

Miscellaneous 14 21Neuronal 10 0Hemangioblastoma 3 5Others 1 16

Total 117 177

FIGURE 3.1 A chart of tumor location in 164 children with intramedullary tumors.

Cervicomedullary

Cervical

Cervicothoracic

Thoracic

Conus

0

10

20

30

40

50

60

70


abdominal pain and undergo extensive gastrointestinal investigations [4]. Theonset of symptoms is often insidious, and symptoms are typically present foraround 9 months. However, high-grade or malignant neoplasms typically havea shorter presentation than indolent low-grade tumors.

Patients may also present with a motor deficit. This is the most common pre-sentation in children with intramedullary tumors (Table 3.2). These deficits canresult in clumsiness, weakness, or frequent falls. In children, this may manifestas motor regression, such as refusal to stand or crawl after having learned to walk.

Scoliosis can also be a presenting complaint. This is seen in one third of chil-dren and young adults [12]. The direction of the scoliosis curve is not specific.Children with scoliosis typically have paraspinal pain, which is unusual forintramedullary tumors. Adult patients typically do not have scoliosis as a pre-senting complaint.

4 DIAGNOSTIC STUDIES

Magnetic resonance imaging (MRI) is the imaging study of choice to identify anintradural spinal cord neoplasm. MRI scans should be performed with intravenouscontrast agents (gadolinium diethylene-triamine-pentacetic acid) and in multipleplanes. These images demonstrate the solid tumor component, associated cysts,and edema. Although MRI does not provide the histological diagnosis, there aresome typical patterns of appearance for intramedullary tumors. Ependymomastend to enhance brightly and homogeneously with contrast (Fig. 3.2). They areoften associated with rostral and caudal cysts. These tumors are centrally locatedwithin the spinal cord. On the other hand, astrocytomas and gangliogliomas havea heterogeneous enhancement pattern (Fig. 3.3). These tumors are often eccen-trically located and produce an asymmetric enlargement of the spinal cord.Intramedullary tumors such as cavernous malformations and hemangioblastomasalso have distinct imaging qualities (Fig. 3.4). These lesions are typically situatednear the dorsal surface of the spinal cord [11]. Hemangioblastomas, regardless ofsize, have a syrinx or associated edema.


TABLE 3.2 Clinical Symptoms Prompting RadiologicalInvestigation in the Author’s Series of 164 Children with an Intramedullary Neoplasm

Symptom/sign Percentage of children

Motor Regression 65.2%

Pain 45.7%

Gait Abnormality 37.2%

Dysesthesia 32.3%

Progessive Scoliosis 32.3%


Computed tomography (CT) studies are reserved only for patients in whichMRI is contraindicated or investigation of the bone anatomy is essential. Thisstudy is useful for the rare tumor that may involve bone and have extension tothe spinal cord. With the advent of MRI, it is very unusual to diagnose intra-medullary neoplasms with this imaging modality. Plain radiographs are manda-tory for patients who present with scoliosis. In addition, young children whoundergo an extensive laminotomy or laminectomy are at risk for developingpostsurgical scoliosis and should be followed with serial radiographs.


FIGURE 3.2 MRI of a 42-year-old male who presented with several months of upper extremityweakness and dysesthesias. MRI appearance consistent with an intramedullary ependymoma.(A) T1-weighted image demonstrates a homogeneously enhancing tumor at C4-C5. (B) T2-weighted image demonstrates the circumscribed tumor with rostral and caudal cysts. (C) The axialT1-weighted image demonstrates the central location of the tumor.


5 SURGICAL MANAGEMENT

5.1 SURGICAL INSTRUMENTS

The traditional method of suction and bipolar cautery for the removal of intra-medullary neoplasms is now supplemented by specialized microinstruments.These instruments have become essential for the microsurgical resection ofspinal cord tumors.

The cavitron ultrasonic aspirator (CUSA; Valleylab, Boulder, CO) uses high-frequency sound waves to fragment and then suction tumor from the probe


FIGURE 3.2 (Continued)


tip [13, 14]. There have been significant advances in this technology. The han-dles have become smaller and lighter for more delicate use in the spinal cord.This allows for tumor removal with only minimal manipulation of the adjacentspinal tissue.

The laser is an excellent surgical adjunct for intramedullary surgery.Although many surgeons do not use this technology, we prefer the Nd:YAGContact Laser System (SLT, Montgomeryville, PA) to other laser systems suchas the argon, CO2, or potassium titanyl phosphate (KTP) systems. The laser isused as a microsurgical instrument with its handpiece and various size andshapes of contact probes. The tip diameters of the probes for neurosurgical usevary from 200 µm to 1.2 mm (Fig. 3.5). The contact probes are useful as ascalpel to perform the myelotomy, to demarcate the glial–tumor interface, andto remove any residual fragments. Unlike other laser systems, there is minimalassociated char and smoke generation. For lipomas and firm intramedullary orextramedullary tumors, the larger probes provide great precision for vaporiza-tion and internal debulking.




5.2 SURGICAL TECHNIQUES

The surgical approach for all intramedullary tumors is an osteoplastic lamino-tomy or laminectomy with the patient in the prone position. For cervical or cer-vicothoracic tumors, the head is fixed in a Sugita (Mizuho, Beverly, MA) orMayfield (OMI, Cincinnati, OH) headholder. Venous hypertension, which maybe significant in obese patients, is minimized using soft gel-rolls under the chest.

The bone opening is done in a way that permits repositioning of the laminaewhen possible. Some authors advocate a laminoplasty with a threadwire saw [15].


FIGURE 3.3 MRI of a 15-year-old male with an intramedullary astrocytoma from C3-C7. (A) T1-weighted sagittal image demonstrates a heterogeneously enhancing tumor of the cervical spine. (B)Axial T1-weighted image typical for an astrocytoma.


However, a craniotome attachment on the Midas (Midas Rex, Fort Worth, TX)drill is an excellent alternative. In patients who have been previously operatedupon, the laminae may not be present for repositioning. For these patients weperform a reopening of the laminectomy with adequate exposure of the boneanatomy. The opening, regardless of a laminotomy or laminectomy, is largeenough to expose the solid component of the tumor. The rostral and caudalcysts do not need to be fully exposed. This opening is planned with intraoper-ative x-rays, and we seldom use fluoroscopy in localizing an intradural tumor.We prefer to use intraoperative x-rays and ultrasound, which allows us to visu-alize the spinal cord in two dimensions, sagittal and axial. Intramedullary astro-cytomas and gangliogliomas have the same echogenicity as the spinal cord. Incontrast, ependymomas tend to be hyperechogenic and can be readily differen-tiated from the spinal cord. This tumor tends to be more visible and in thecenter of the spinal cord. Ultrasound is helpful in identifying the associatedtumor cyst(s). If the bone removal does not fully expose the solid tumor com-ponent, the laminectomy or laminotomy is extended prior to opening the dura.

The dura is then opened in the midline. The spinal cord should be expandedand may occasionally be rotated. A surgeon should be wary of nonexpandedspinal cords. In these cases, one should suspect a nonneoplastic process. Theasymmetric expansion and rotation of the spinal cord may make the identifica-tion of the midline difficult. In those exceptional cases with an asymmetric




tumor and rotated spinal cord, a myelotomy may be performed through thedorsal root entry zone by localizing the midline using the neurophysiologicaltechnique of “dorsal column mapping” (see Chapter 7).

The neoplasm is typically located several millimeters underneath the dorsalsurface. The contact laser is used to perform the myelotomy with minimalneural injury, and it does not interfere with the intraoperative neurophysiolog-ical monitoring. Intramedullary tumors have different appearances, such as tex-ture and color, which help the neurosurgeon differentiate the tumor type.


FIGURE 3.4 MRI of 21-year-old girl with a cervical hemangioblastoma. (A) T1-weighted sagittalimage with gadolinium demonstrates the enhancing small dorsally situated tumor which abuts thepial surface and the extensive syrinx. (B) Axial T1-weighted image demonstrates the small dorsallysituated tumor.


5.2.1 Astrocytomas and Gangliomas

Astrocytomas or gangliogliomas have a gray-yellow appearance. A true planebetween tumor and normal spinal cord does not exist. The surgeon shouldmake no effort to define this true interface because it results in hazardousmanipulation of normal spinal cord tissue. Ependymomas are typically red ordark gray in color. These neoplasms have a clear margin from the surroundingspinal cord. This interface can be readily separated with a plated bayonet [16]or the scalpel probe of the contact laser.

Once the tumor is exposed, a biopsy is taken for immediate histologicalexamination. This information may be crucial in deciding the extent of tumorresection if the tumor is a malignant glioma or inflammatory process. For malig-nant gliomas, a more conservative approach, to limit any potential motordeficits, is undertaken. The goal is tumor debulking with preservation of motorfunction.




Tumor removal for low-grade astrocytomas and gangliogliomas begins afterthe initial myelotomy is performed. An internal debulking with the CUSA isdone to reduce the tumor volume. The resection of astrocytomas is initiated atthe midportion rather than the tumor poles. The rostral and caudal poles arethe least voluminous, and manipulation at these locations may be the most dan-gerous to the normal spinal cord tissue. Then, using the suction or contactlaser, the tumor is gently removed from the surrounding spinal cord tissue.These tumors do not have a cleavage plane, although in some areas a plane mayexist between tumor and normal spinal tissue. These tumors tend to displacethe motor tracts anteriorly or laterally. The surgeon should be aware of thesepathways during tumor resection.

5.2.2 Ependymomas

Ependymomas, which are more common in adults than in children, are typi-cally located in the center of the spinal cord. They frequently have a rostral orcaudal cyst. These tumors have a distinct cleavage plane that exists between thetumor and the normal spinal cord. After the myelotomy is performed, this planecan be identified most readily at the rostral or caudal pole. The contact laser isuseful in defining this cleavage plane and in cutting the adhesions surroundingthe tumor. The laser provides tactile sensation feedback and cuts tissue withminimal traction. Since the blood supply to this tumor comes from the ventralsurface, extreme care is taken not to injure the anterior spinal artery.


FIGURE 3.5 Photograph showing the tip of the laser probe (approximately 200 µm).


The rostral-caudal length of the tumor does not influence the functional out-come after tumor resection. We have found the removal of a small tumor witha wide girth to be more difficult than removal of a long narrower tumor. Thisobservation corresponds to previous reports that spinal cord atrophy is a poorprognostic factor [17].

5.2.3 Vascular Tumors

Hemangioblastomas in the spinal cord, regardless of size, are often associatedwith significant edema and syrinx formation. The resection of these lesions issimilar to resection of their intracranial counterpart. The lesion should beresected in a circumferential fashion. The tumor surface can be coagulated toallow for the manipulation of the lesion; however, this tumor should not andcannot be debulked from within. We do not embolize these tumors, but a pre-operative angiogram is still performed for large lesions. This is the only tumortype for which we do not stop surgery, regardless of information obtained fromintraoperative neurophysiological monitoring, until the tumor is completelyremoved. Residual tumor may predispose the patient for future intraspinalhemorrhages.

Cavernous malformations, similar to hemangioblastomas, are typically locatedon the dorsal surface of the spinal cord [11]. A bluish discoloration underneaththe pial surface identifies the lesion. This vascular malformation is resected in aninside-out fashion, similar to the technique for astrocytomas. These lesions do notusually bleed during the resection; thus the CUSA or suction cautery can be safelyused for their removal. Cavernous malformations are usually surrounded by a gli-otic plane that permits delineation from the surrounding spinal cord tissue. Thesevascular malformations are quite uncommon in children. When these lesions pre-sent in the pediatric population, there is high probability for multiple intracraniallesions [11].

5.2.4 Intramedullary Lipomas

Intramedullary lipomas require a different surgical strategy than glial neo-plasms. Although this tumor may appear well demarcated from the adjacentspinal tissue, these lesions are densely adherent. Thus total removal is fraughtwith neurological compromise. The contact laser is typically used to debulkthese tumors. The laser vaporizes the fatty tissue without any surgical traumato the spinal cord. The surgeon should only perform a debulking of this tumor,because further tumor growth is unlikely [18].

Following intramedullary tumor removal, hemostasis is obtained with warmsaline irrigation and avitene. The dura is then closed primarily in a water-tightfashion. If an osteoplastic laminotomy was performed, the laminae are replaced



and secured with a nonabsorbable suture. One tissue layer must be closed in awater-tight fashion, and the muscle and fascial closure must not be under ten-sion. A subcutaneous drain is placed only for reoperations. Patients who havehad previous surgery and radiation therapy are at considerable risk for wounddehiscence and cerebrospinal fluid leak. These patients are maintained atbedrest for several days to allow for wound healing.

6 OUTCOME FOLLOWING SURGERY

The major neurological hazard following intramedullary tumor surgery isparalysis. The incidence of paralysis is related to the preoperative motor status[6, 19]. Patients who have no or minimal preoperative motor deficits have lessthan 1% incidence of this postoperative complication. Thus today’s surgery onspinal cord tumors is relatively safe when the available microinstruments andintraoperative neurophysiological monitoring are used. Almost all patientsundergoing gross total resection of intramedullary spinal cord tumors experi-ence some immediate postoperative deterioration of neurological function. Thisneurological deterioration is typically temporary, and recovery occurs within afew hours, days, or weeks [20–23].

The incidence of clinical improvement after surgery is higher in patientsundergoing total resection than in patients undergoing partial resection [24].In our series the extent of resection, gross total (>95%) or subtotal resection(80–95%), did not significantly affect the long-term outcome. On the otherhand, patients who underwent a partial resection or biopsy (<80%) fared sig-nificantly worse than those with radically removed tumors. These conclusionsfor intramedullary astrocytomas have been supported by others [25]. On theother hand, radical resection of malignant astrocytomas has failed to show anybenefit [26–28]. In a review of the literature, patients with an intramedullaryanaplastic astrocytoma or glioblastoma do not survive beyond 2 years, despiteaggressive adjuvant radiotherapy and chemotherapy [25]. Thus, if at the timeof surgery the frozen histology returns as a high-grade glioma, we prefer to per-form a conservative resection of these neoplasms with preservation of motorfunction predicted intraoperatively by monitoring motor evoked potentials (seeChapters 2 and 4).

The extent of resection is most beneficial for ependymomas. Many studieshave shown substantial benefits associated with total resection of intra-medullary ependymomas [8, 20, 27, 29, 30]. Survival for patients with ependy-momas in one study was 219 months for patients undergoing total resection asopposed to 130 months for a subtotal removal [31]. These tumors, which havea cleavage plane, should be totally resected, and radiation therapy should beavoided.



Despite gross total resections for intramedullary neoplasms, residual micro-scopic fragments are left in the resection bed. These residual fragments mayremain dormant or involute over time. There is no evidence that radiation ther-apy improves the outcome of low-grade astrocytomas or ependymomas [9, 21,32, 33]. There is abundant evidence that radiation has deleterious effects on thenervous and osseous system [34–36]. There have been two studies that docu-ment alterations in motor and sensory evoked potentials in patients who havereceived radiation therapy [37, 38]. Some authors recommend radiotherapy forall intramedullary neoplasms [39, 40]; however, no prospective study has beenperformed comparing the results of radiotherapy. We recommend radiationtherapy only for malignant tumors, patients with documented postoperativerapid tumor regrowth, and in those cases where substantial tumor remains andfurther surgery is not safely feasible. Although neuraxis radiation therapy isrecommended for malignant tumors, these neoplasms invariably progress.Unfortunately, chemotherapy for these neoplasms has not been shown to bebeneficial.

7 SURGICAL COMPLICATIONS

7.1 DETERIORATION IN FUNCTIONAL OUTCOME

The earlier the diagnosis and radical resection of an intramedullary tumor, thegreater the likelihood of preserving the patient’s neurological function [6].Since 1987, no patient undergoing surgery who was functioning preoperativelyat a modified McCormick Grade I level [41] deteriorated more than one grade.The incidence of deteriorating more than one functional grade for the otherpatients was 8% in our study of 164 children, and most patients who deterio-rated had significant preoperative deficits. This confirms our thesis that unnec-essary delays in surgery may reduce the recovery potential of the spinal cord.

7.2 CEREBROSPINAL FLUID LEAK

This complication is unusual in most cases of intramedullary neoplasms, exceptfor patients who have been previously operated on or who have received radio-therapy. In these patients there is a risk for wound dehiscence and cerebrospinalfluid fistula. Early in our experience we had several patients with poor woundhealing and the development of meningitis or wound infection. We now useplastic surgical techniques for these patients [42]. We close the fascia in awater-tight fashion and without tension. This closure may require relaxing inci-sions to provide a tension-free closure. Subcutaneous drains are placed to allow



for the wound to heal. These patients are maintained at bed rest for several daysto avoid this complication.

8 CONCLUSION

Surgical resection for intramedullary neoplasms has evolved since the initialreport of Elsberg. With the advent of the microsurgical technique, imagingtechnology, and intraoperative neurophysiology, the radical resection ofintramedullary neoplasms is a safe and effective treatment. In particular, theneurophysiological monitoring of motor pathways is extremely helpful inachieving a radical resection for these intramedullary tumors. The functionaloutcome of surgery is best correlated with the preoperative status; thussurgery should be performed early prior to onset of severe motor deficits. Thepresent surgical adjuncts allow us to recommend radical resection for themajority of intramedullary neoplasms. This approach should be the standardfor intramedullary tumors because it provides excellent progression-free sur-vival. Adjuvant radiation and chemotherapy should only be administered formalignant gliomas.

Included with the accompanying CD is a video comparing the noise artifactsaffecting the intraoperative recordings when using the bipolar cautery, as com-pared to the artifact-free recordings when the contact laser is being used (chooseChapter 3 from the accompanying CDs main menu).

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3. Elsberg, C.A., and Beer, R. (1911). The operability of intramedullary tumors of the spinal cord.A report of two operations with remarks upon the extrusion of intraspinal tumors. Am. J. Med.Sci., 142, 636.

4. Wood, E.S., Berne, A.S., and Taveras, J.M. (1954). The value of radiation therapy in the man-agement of intrinsic tumors of the spinal cord. Radiology, 63, 11–24.

5. Miller, D.C. (2000). Surgical pathology of intramedullary spinal cord neoplasms. J. Neuro.-Oncol.,47, 189–194.

6. Constantini, S., Miller, D.C., Allen, J.C., Rorke, L.B., Freed, D., and Epstein, F.J. (2000). Rad-ical excision of intramedullary spinal cord tumors: Surgical morbidity and long-term follow-up evaluation in 164 children and young adults. J. Neurosurg. (Spine), 93, 183–193.

7. Greenwood, J. Jr. (1967). Surgical removal of intramedullary tumors. J. Neurosurg., 26, 276–282.8. Guidetti, B., Mercuri, S., and Vagnozzi, R. (1981). Long-term results of the surgical treatment

of 129 intramedullary spinal gliomas. J. Neurosurg., 54, 323–330.



9. Epstein, F., and Epstein, N. (1982). Surgical treatment of spinal cord astrocytomas of children.J. Neurosurg., 57, 685–689.

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11. Deutsch, H., Jallo, G., Faktorovich, A., and Epstein, F. (2000). Spinal intramedullary caver-noma: Clinical presentation and surgical outcome. J. Neurosurg. (Spine 1), 93, 65–70.

12. Yao, K., Kothbauer, K., Bitan, F., Constantini, S., Epstein, F., and Jallo, G. (2000). Spinal defor-mity and intramedullary tumor surgery. Child’s Nerv. Syst., 16, 530.

13. Flamm, E.S., Ransohoff, J.P., Wuchinich, D., and Broadwin, A. (1978). Preliminary experiencewith ultrasonic aspiration in neurosurgery. Neurosurgery, 2, 240–245.

14. Constantini, S., and Epstein, F.J. (1996). Ultrasonic dissection in neurosurgery. In “Neuro-surgery” (R.H. Wilkins, and S.S. Rengachary, eds.), vol. 1, pp. 607–608. McGraw-Hill, NewYork.

15. Hara, M., Takayasu, M., Takagi, T., and Yoshida, J. (2000). En bloe laminoplasty performedwith threadwire saw: Technical note. Neurosurgery, 48, 235–239.

16. Epstein, F.J., and Ozek, M. (1993). The plated bayonet: A new instrument to facilitate surgeryfor intra-axial neoplasms of the spinal cord and brain stem. Technical note. J. Neurosurg., 78,505–507.

17. Hoshimaru, M., Koyama, T., Hashimoto, N., and Kikuchi, H. (1999). Results of microsurgicaltreatment for intramedullary spinal cord ependymomas: Analysis of 36 cases. Neurosurgery, 44,264–269.

18. Lee, M., Rezai, A.R., Abbott, R., Coelho, D.H., and Epstein, F.J. (1995). Intramedullary spinalcord lipomas. J. Neurosurg., 82, 394–400.

19. Kothbauer, K., Deletis, V., and Epstein, F.J. (1997). Intraoperative spinal cord monitoring forintramedullary surgery: An essential adjunct. Pediatr. Neurosurg., 26, 247–254.

20. Brotchi, J., DeWitte, O., Levivier, M., Baleriaux, D., Vandesteene, A., Raftopoulos, C., Flament-Duran, J., and Noterman, J. (1991). A survey of 65 tumors within the spinal cord: Surgical resultsand the importance of preoperative magnetic resonance imaging. Neurosurgery, 29, 652–657.

21. Goh, K.Y., Velasquez, L., and Epstein, F.J. (1997). Pediatric intramedullary spinal cord tumors:Is surgery alone enough? Pediatr. Neurosurg., 27, 34–39.

22. Herrmann, H.D., Neuss, M., and Winkler, D. (1988). Intramedullary spinal cord tumorsresected with CO2 laser microsurgical technique: Recent experience in fifteen patients. Neuro-surgery, 22, 518–522.

23. Samii, M., and Klekamp, J. (1994). Surgical results of 100 intramedullary tumors in relationto accompanying syringomyelia. Neurosurgery, 35, 865–873; discussion 873.

24. Xu, Q.W., Bao, W.M., Mao, R.L., and Yang, G.Y. (1996). Aggressive surgery for intramedullarytumor of cervical spinal cord. Surg. Neurol., 46, 322–328.

25. Nadkarni, T.D., and Rekate, H.L. (1999). Pediatric intramedullary spinal cord tumors: Criti-cal review of the literature. Child’s Nerv. Syst., 15, 17–28.

26. Cohen, A.R., Wisoff, J.H., Allen, J.C., and Epstein, F. (1989). Malignant astrocytomas of thespinal cord. J. Neurosurg., 70, 50–54.

27. Cooper, P.R. (1989). Outcome after operative treatment of intramedullary spinal cord tumorsin adults: Intermediate and long-term results in 51 patients. Neurosurgery, 25, 855–859.

28. Houten, J.K., and Cooper, P.R. (2000). Spinal cord astrocytomas: Presentation, managementand outcome. J. Neuro.-Oncol., 47, 219–224.

29. Cristante, L., and Herrmann, H.D. (1994). Surgical management of intramedullary spinal cordtumors: Functional outcome and sources of morbidity. Neurosurgery, 35, 69–76.

30. Whitaker, S.J., Bessel, E.M., Ashley, S.E., Bloom, H.J.G., Bell, B.A., and Brada, M. (1991). Post-operative radiotherapy in the management of spinal cord ependymoma. J. Neurosurg., 74,720–728.



31. Innocenzi, G., Raco, A., Cantore, G., and Raimondi, A. J. (1996). Intramedullary astrocytomasand ependymomas in the pediatric age group: A retrospective study. Child’s Nerv. Syst., 12,776–780.

32. Stein, B.M. (1979). Surgery of intramedullary spinal cord tumors. Clin. Neurosurg., 26, 529–542.33. Stein, B.M. (1983). Intramedullary spinal cord tumors. Clin. Neurosurg., 30, 717–741.34. Clayton, P.E., and Shalet, S.M. (1991). The evolution of spinal growth after irradiation. Clin.

Oncol., 3, 220–222.35. Duffner, P.K., Horowitz, M.E., Krischer, J.P., Friedman, H.S., Burger, P.C., Cohen, M.E.,

Sanford, R.A., Mulhern, R.K., James, H.E., Freeman, C.R., Seidel, F.G., and Kun, L.E. (1993).Postoperative chemotherapy and delayed radiation in children less than three years of age withmalignant brain tumors. N. Eng. J. Med., 328, 1725–1731.

36. Marcus, R.B., and Million, R.R. (1990). The incidence of myelitis after irradiation of the cer-vical spinal cord. Int. J. Rad. Oncol. Biol. Phys., 19, 3–8.

37. Morota, N., Deletis, V., Constantini, S., Kofler, M., Cohen, H., and Epstein, F.J. (1997). Therole of motor evoked potentials during surgery for intramedullary spinal cord tumors. Neuro-surgery, 41, 1327–1336.

38. De Scisciolo, G., Bartelli, M., Magrini, S., Biti, G.P., Guidi, L., and Pinto, F. (1991). Long-termnervous system damage from radiation of the spinal cord: An electrophysiological study. J.Neurol., 238, 9–15.

39. O’Sullivan, C., Jenkin, R.D., Doherty, M.A., Hoffman, H.J., and Greenberg, M.L. (1994). Spinalcord tumors in children: Long-term results of combined surgical and radiation treatment. J.Neurosurg., 81, 507–512.

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41. McCormick, P.C., and Stein, B.M. (1990). Intramedullary tumors in adults. Neurosurg. Clin.N. Am., 1, 609–630.

42. Zide, B.M., Wisoff, J.H., and Epstein, F.J. (1987). Closure of extensive and complicatedlaminectomy wounds: Operative technique. J. Neurosurg., 67, 59–64.



C H A P T E R 4

Motor Evoked PotentialMonitoring forIntramedullary SpinalCord Tumor SurgeryKARL F. KOTHBAUER

Hyman-Newman Institute for Neurology and Neurosurgery,Beth Israel Medical Center, New York

1 Introduction2 Neurophysiology

2.1 D Waves (“Epidural MEPs”)2.2 Muscle MEPs

3 Anesthesia4 Safety5 Clinical Assessment and Correlation6 Practical Surgical Application of Intraoperative

Neurophysiological Information6.1 Feasibility and Practicality of Monitoring6.2 Interpretation of D Wave Data6.3 Interpretation of Muscle MEP Data6.4 Combined Interpretation of D Wave and Muscle

MEP Data6.5 Influence of MEP Monitoring on Extent

of Resection6.6 Observations on the Behavior of MEPs During

Intramedullary Spinal Cord Tumor Surgery7 Illustrative Cases

7.1 Case 17.2 Case 27.3 Case 37.4 Case 4



74 Karl F. Kothbauer

8 SummaryAcknowledgmentsReferences

ABSTRACT

This chapter reviews several important issues concerning intraoperative motorevoked potential (MEP) monitoring of spinal cord surgery. First, it gives an overviewof the technique of MEP monitoring in a surgical environment. Second, it reviewsthe evidence for accurate representation of the pre- and postsurgical motor status bycombined epidural and muscle MEP monitoring. Third, it addresses the intraopera-tive impact of the neurophysiological information on the course of the procedure(i.e., how “useful” monitoring is to the surgeon).

Motor potentials are evoked by transcranial electrical motor cortex stimulation.With the single-stimulus technique, D waves are elicited that are recorded from thespinal cord. With the train-stimulus technique, muscle MEPs are elicited that arerecorded from limb muscles. The amplitude of the D waves and the presence orabsence of muscle MEPs are the critical parameters for MEP interpretation. The prac-tical procedures for MEP recording fit well into a neurosurgical environment, and theintraoperative interpretation and application of neurophysiological information arefast and straightforward. MEP monitoring is almost always possible in a patient whois not severely disabled already prior to surgery.

Pre- and postoperative clinical motor findings correlate with intraoperative MEPdata. As a result, correct prediction of the clinical outcome at any given time duringthe operation is possible with considerable certainty (the sensitivity of muscle MEPsfor postoperative motor deficits is next to 100%, and its specificity is about 90%).Thus, MEP data do reflect the clinical “reality” for a patient.

Loss of muscle MEPs, interpreted in combination with stepwise decreases in theD wave amplitude, leaves a considerable window of warning between the firstchanges in recordings and a permanent injury to the essential motor pathways. Thusthe surgical strategy can be adapted before irreversible neurological damage occurs.On the other hand, present and stable recordings allow complete resection of tumorswith confidence about the integrity of the motor pathways. These two features makeMEP monitoring during intramedullary surgery very useful. Use of this monitoringtechnique should become a standard for this type of surgery.

1 INTRODUCTION

Neurosurgeons have great respect for the spinal cord. The resection of intra-medullary tumors of the spinal cord is believed to carry a high risk for surgicaldamage and subsequent neurological dysfunction because the cord is a delicatestructure with tightly packed essential pathways and neural circuits. Going intothe cord with surgical instruments and manipulation involves the possibility ofselective damage to the motor pathways, the sensory pathways, or the cord’sintrinsic neural apparatus. Since paralysis, the loss of voluntary motor control, isthe most feared neurological complication, it is essential to have a tool available


Motor Evoked Potential Monitoring for Intramedullary Spinal Cord Tumor Surgery 75

that directly and selectively monitors the functional integrity of the motorsystem during resection of intracord lesions. Intraoperative neurophysiologicalmonitoring with motor evoked potentials (MEPs) is exactly this tool.

The first impulse to use evoked potentials to assess functional aspects of thespinal cord during surgical procedures came from orthopedic surgeons [1, 2].Somatosensory evoked potentials (SEPs) were the only monitoring methodol-ogy available at the time. From the present “digital age” perspective, the diffi-culties with slow recording hardware, difficult documentation, and lack ofexperience must have been formidable. In addition, a serious conceptual prob-lem comes with monitoring of SEPs: they reflect, of course, the functionalintegrity of the sensory pathways and therefore provide only indirect informa-tion on the motor pathways. This may be acceptable for orthopedic surgery, inwhich external cord compression would be the mechanism of injury in mostcases. SEP monitoring is still used as a means of “overall” spinal cord monitor-ing in centers where MEP monitoring is not available. And SEP monitoring hasindeed been beneficial in large numbers of spinal orthopedic operations [3].However, when the resection of lesions within the cord is attempted, there is aconsiderable risk of selective damage to the motor tract that is not reflected bychanges in SEP recordings [4, 5]. Furthermore, change in or loss of SEPsduring intramedullary operations is quite common and is certainly associatedwith the need to enter the cord through the dorsal midline [6], but it does notcorrelate with the motor outcome. And, of course, there is the problem ofrecording delay, since with averaging times the identification of injury can lagconsiderably behind the progress of the surgical procedure. Because of thisknown shortcoming of SEPs, to this day many neurosurgeons have the some-what unreflected view of neurophysiological monitoring in general: whenchanges are recognized the damage has been done, and it is too late for anyintervention anyway.

With Merton’s first paper on electrically evoked MEPs [7], neurosurgeonsquickly understood the potential of this technique for the direct and selectiveintraoperative assessment of motor pathways in both the brain and the spinalcord. The early papers still reflect the methodological difficulty associated withmaking use of the new method in the operating room [8]. Going back to con-cepts of the motor system developed since the 1950s [9, 10], this direct motormonitoring technique became based on firm ground, the concept of corti-cospinal recordings that reflect a small but essential fiber population in thecord. This was the introduction of the D wave to the operating room [11–14].In addition to this recording technique, which requires recording from the cordwith an epidurally placed electrode, muscle recording techniques were intro-duced with magnetic [15] and electrical [16] stimulation of the brain. Anesthe-sia posed a major problem, but the development of a multipulse or train-stimulustechnique [17, 18] resolved this difficulty.



In the 1990s the understanding of neurophysiology, interpretation, andsafety increased, and the experience with practical application improved. Sev-eral series provided first evidence that intraoperative MEP monitoring reallyworks and is indeed useful for the experienced neurosurgeon [19–23]. Ourgroup has gained considerable experience in the combined use of D wave andmuscle MEP monitoring [21, 23–27].

Based on the neurosurgical and neurophysiological experience of severalhundred operations on spinal cord tumors from 1996 to 2000, and on the accu-mulated scientific evidence, this chapter attempts to illustrate that MEP moni-toring of the functional integrity of the motor pathways during intramedullarysurgery is one of the most impressive, accurate, and useful evoked potentialmonitoring technique in use today. MEP monitoring can be safely done, it rep-resents the clinical “reality,” and its concept provides a warning window ofreversible change. This allows for spinal cord tumor resection with muchgreater safety from neurological injury and with much greater confidence forradical resection during the operation.

2 NEUROPHYSIOLOGY

The intraoperative MEP monitoring techniques currently used for intramed-ullary surgery are the result of a long and ongoing development to which manyindividuals have contributed [7, 9, 10, 12, 14, 16, 18–21, 24–26, 28–31].

Motor potentials are evoked with transcranial electrical stimulation. Thestimulus points are C3, C4, C1, C2, Cz, and a point 6 cm in front of Cz (Inter-national 10-20 EEG electrode system [32]) (Fig. 4.1A). Electrical stimulationis performed with constant current square wave stimuli of 500 µs duration andintensities between 15 and 200 mA.

2.1 D WAVES (“EPIDURAL MEPS”)

D waves, or “epidural MEPs” [9], are elicited with single stimuli. This is thereforecalled the “single-stimulus technique” (Fig. 4.1B). Responses are recorded fromthe spinal cord with an electrode (Type JX-330, Arrow International, Inc., Read-ing, PA) inserted into the spinal epidural space by the surgeon after the laminec-tomy. One electrode is placed caudally, and if the tumor location permits it,another one is placed cranially as a control (Fig. 4.1C). The signals are amplified10,000 times, the filter bandpass is set from 1.5 to 1700 Hz, and responses arerecorded within 20 ms epochs. Baseline recordings are obtained before openingof the dura. The signal usually requires no averaging but may, at times, require afew (averaged) responses. Stimulation is repeated at a rate of 0.5 to 2 Hz duringthe critical part of the procedure. This provides fast, “real-time,” feedback.



The parameter monitored in epidural recordings is the peak-to-peakamplitude of the D wave. It has been shown that a decrease of more than 50%from the baseline value is associated with a long-term motor deficit [25].Latency changes of the D wave are rare and are due to nonsurgical influencessuch as temperature [24] (see also Chapter 2, Fig. 2.7, page 38). A change in

FIGURE 4.1 Motor evoked potential techniques. (A) Schematic view of the stimulus points fortranscranial electrical stimulation of the motor cortex. (B) Schematic representation of the singlestimulus and the train stimulus techniques. (C) Cranial and caudal epidural D wave recording. (D)Muscle MEP recording.



stimulus intensity also alters the D wave latency: higher intensities lead toshorter latencies, implying that the corticospinal tract fiber activation occursdeeper in the white matter of the brain [14].

2.2 MUSCLE MEPS

Muscle MEPs are also elicited with transcranial electrical stimulation. A shorttrain of five to seven stimuli, with a 4 ms interstimulus interval [33, 34], isused. Thus this technique is called the “train stimulus technique”(Fig. 4.1B),or multipulse technique [22]. Compound muscle action potentials (CMAPs)are recorded with needle electrodes from target muscles in all four extremities(e.g., the thenar and tibialis anterior muscles) (Fig. 4.1D). More recently, theabductor hallucis has proven to be useful, probably because this muscle has richpyramidal innervation [35]. The signals are amplified 10,000 times and arerecorded on epochs of 100 ms with a filter setting. CMAPs are amplified 10,000times and are recorded during a 100 ms epoch with a 1.5 to 853 Hz filter set-ting. Baseline recordings are obtained after positioning of the patient on theoperating table. Like the D waves, muscle MEP signals do not require averag-ing and can be repeated at a rate of 0.5 to 2 Hz. Therefore, real-time feedbackis possible here as well. With the focal anode as the stimulating electrode, amontage of C1/2 or C2/1 is tried first to elicit muscle MEPs in all four extrem-ities. In individual cases, C3/4, C4/3, or CZ/6 is used as an alternative stimula-tion point. Muscle MEPs are recorded in an alternating fashion with D waves.

The principle of evoking muscle responses follows from the D wave concept:each individual electrical stimulus on the motor cortex, either with exposedcortex or with transcranial stimulation [13], elicits a D wave in the corticospinaltract. A train of five stimuli, with an interstimulus interval of 4 ms, elicits fiveD waves that travel down the corticospinal tract 4 ms apart. Thus the spinal α-motorneurons are hit by five consecutive descending volleys and their mem-brane potential is elevated above firing threshold. This mechanism has beenshown with direct intracellular recordings from α-motorneurons in primateanimal experiments [10]. The additional role of facilitation of I waves [33, 34]is discussed in a separate chapter (see Chapter 2).

The parameter monitored during spine and spinal cord surgery is the pres-ence or absence of muscle MEPs in the target muscles. The stimulus intensitytypically ranges from 15 to 200 mA. This all-or-none concept has been adoptedfor two reasons. First, in contrast to epidural MEPs, which show little ampli-tude variation [36], the variability of muscle MEP amplitudes is tremendous[19, 30, 37]. Thus defining a threshold amplitude below which one expects anintraoperative injury would be extremely difficult. Second, our experience aswell as the evidence in the reported series (even with varying stimulus patterns)



has indicated that a motor deficit occurred only when the muscle response waslost [16, 19, 30]. Our data do not support the idea of using an increase of muscleMEP stimulus thresholds as a monitoring parameter [22]. The thresholds foreliciting epidural MEPs fluctuate very little. On the contrary, thresholds formuscle MEPs vary considerably during an individual procedure. However, onlythe presence or absence of muscle responses consistently correlates with theclinical findings. Experience with monitoring supratentorial surgeries is some-what different (see Chapter 15).

All recordings in our institution are obtained with the Axon Sentinel-4 EPanalyzer (Axon Systems Inc., Hauppauge, NY) equipped with a dedicated soft-ware for controlling transcranial stimulation paradigms.

3 ANESTHESIA

The effects of anesthetic agents on neurophysiologic recordings is extensivelycovered in a separate chapter of this book (see Chapter 17). Therefore, only abrief outline of the principles of anesthesia compatible with neurophysiologi-cal monitoring is given here. An anesthesia regimen that allows for intraopera-tive MEP monitoring consists of a constant infusion of propofol (usually in adose of about 100–150 µg/kg/min) and fentanyl (usually around 1 µg/kg/hr).The use of propofol for anesthesia with MEP monitoring has been reported withvarious stimulation techniques [38–42]. Nitrous oxide not exceeding 50 Vol%can be used. Bolus injections of both intravenous agents should be avoidedbecause this temporarily disrupts the generation of muscle MEPs, which areparticularly important during the critical resection part of the operation. Halo-genated anesthetics cannot be used [17, 18]. The use of short-acting musclerelaxants must be limited to the period of intubation.

Partial myorelaxation is used by some groups [30], but there is no convinc-ing evidence that its use makes management of anesthesia easier or safer. Thishas been a controversial issue, and our group has been subject to considerablecriticism in many discussions. Many neurosurgeons are still very reluctant toaccept even the possibility of slight movement during dissection.

Why should we avoid muscle relaxation? With the patient fully relaxed,muscle MEP monitoring is impossible. “Controlled” relaxation would add anuncontrollable variable in the interpretation of MEPs that would reduce thespecificity of muscle MEP monitoring. On the other hand, it is still unlikely thatpatient movement from stimulation can be completely avoided. In other words,controlled relaxation combines poor monitoring with poor relaxation. Ourexperience has been that relaxation is not necessary once both surgeon andanesthesiologist are used to working without it. In our practice we have notencountered problems because muscle relaxation was not used.



4 SAFETY

Aside from direct neural tissue damage [18, 43], the main safety concernwith the use of transcranial electrical multipulse stimulation has been theissue of seizures. None of our patients have had an epileptic event. There areno reports in the literature about intraoperative seizure induction with tran-scranial electrical stimulation using either a single or a train stimulationtechnique.

The term kindling has been indiscriminately used in this context. Kindlingis an experimental model that refers to the induction of self-perpetuatingepileptic foci in experimental animals. It requires daily repeated electrical stim-ulation at a rate of 50 Hz for several seconds. This paradigm is different fromthe MEP train stimulation paradigm of 250 Hz for 25 ms (Fig. 4.1B). In addi-tion, kindling of an epileptic focus requires a long period of time (weeks tomonths), particularly in primates [44], and, to our knowledge, it has not beenshown to occur in humans. Furthermore, the energy necessary to induce aseizure in electroconvulsive therapy (also with 50 Hz stimulation applied forseveral seconds) is two orders of magnitude higher than the overall energy usedfor MEP monitoring [45].

All data reported so far, as well as the theoretical concept of transcranialelectrical stimulation with a short high-frequency train to elicit muscle MEPs,indicate an extremely low risk of inducing seizures. The only adverse eventsthat we have experienced are minor laceration and hematoma of the tongue asa result of strong contraction of the masticatory muscles due to direct stimula-tion from the cranial stimulation electrodes. For the most part, this has beenavoided by tongue protection with a padded oropharyngeal tube.

Complications such as injury or infection due to electrode placement orstimulation, or spinal epidural hematomas resulting from placement ofepidural electrodes, have not been reported and have not occurred in ourexperience.

5 CLINICAL ASSESSMENT AND CORRELATION

From 1996 to 2000, about 250 operations for removal of intramedullary spinalcord tumors were performed with the use of intraoperative neurophysiologicalmonitoring at our institution. The majority of patients were either children oryounger adults, with a median overall age of about 29 years (1–75 years). Thevast majority of spinal cord tumors are low-grade astrocytomas in children andependymomas in adults. Gangliogliomas, dermoids, hemangioblastomas, caver-nomas, and other lesions also occur. Historically, malignant spinal cord tumors



are rare. The median size of the neoplasms is a segmental extension of fourspinal segments (range 1–12). In our practice about one operation in five is areoperation.

Usually pre- and postoperative motor function is classified as normal (nofocal motor deficit), slightly paretic (motor deficit not exceeding 4/5 and notsignificantly impairing the extremity’s function, walking not impaired), severelyparetic (motor deficit 3/5 or worse, significantly impaired function of extrem-ity, or inability to walk), and plegic (0/5 or 1/5). This is in principle consistentwith the McCormick scale [46].

The extent of surgical resection is assessed as gross-total resection (90%resection or more), subtotal resection (50–90%), partial resection (<50%), orbiopsy based upon the early postoperative MRI.

In a previously published series [23] of 100 consecutive operations of spinalcord tumors, 92 of the 100 patients had a normal or slightly impaired motorstatus before surgery. In all of these 92 cases, muscle MEPs could be recordedat the beginning of surgery (“baseline”). Epidural MEPs were recordable in 59of the 86 cases not involving the conus medullaris. Eight patients had severemotor deficits or were paralyzed. None of them had recordable MEPs (neitherepidural nor from muscle). In no preoperatively paralyzed extremity was thereever a muscle MEP recordable.

Postoperatively, a short-term motor status deterioration is noted in aboutevery third patient (35 of 92 patients, or 38%, in the aforementioned series[23]). A severe permanent neurological dysfunction occurred as a direct resultof the operation in only 2 of about 250 patients (unpublished data). Therefore,the risk of paraplegia following resection of a spinal cord tumor is lower thanis commonly believed. These changes in clinical status were correctly reflectedby the intraoperative MEP findings.

6 PRACTICAL SURGICAL APPLICATIONOF INTRAOPERATIVENEUROPHYSIOLOGICAL INFORMATION

6.1 FEASIBILITY AND PRACTICALITY OF MONITORING

Electrodes are attached to the patient at the same time that the anesthesia prepa-rations (intubation, intravenous and intra-arterial lines) are done. Additionaltime, if any, required for monitoring preparations is minimal. The epiduralrecording electrodes are placed by the surgeon during the operation from thesurgical field to a preamplifier attached to the end of the operating table. This does



not disturb the dissection. Occasionally, scarring from a previous surgery pro-hibits insertion of a recording electrode. In terms of monitorability, practicallyall patients without severe preoperative motor deficits can be monitored witheither D waves or muscle MEPs or both. The recordings are usually robust(between 10 and 70 µV amplitudes of epidural and up to 2 mV in muscle MEPs).Changes due to nonsurgical influences (intravenous bolus of anesthetic, tem-perature or blood pressure changes) can be recognized by following these para-meters together with the anesthesiologist.

Intraoperatively, the combined data of epidural and muscle MEPs indicatejeopardized functional integrity of the motor pathways at some point during theprocedure in almost every other patient with monitorable responses. In abouta third of all cases, these changes remain until the end of the operation and thencorrelate with a temporary motor deficit. In the remainder of cases the changesare reversible and correlate with intact motor function when the patient awakesfrom anesthesia.

6.2 INTERPRETATION OF D WAVE DATA

Two factors are important for interpretation of intraoperative D wave record-ings: the presence of the D wave and, when it is present, its peak-to-peakamplitude. The monitorability of the D wave and the significant intraoperativedecline of its amplitude have been shown to be of predictive value for motoroutcome after surgery for intramedullary spinal cord lesions [25]. In about twothirds of the patients with nonconus tumors, a D wave is recordable [23, 25].(Since D waves are generated by the corticospinal tract axons, conus tumors arenot monitorable with epidural MEPs.)

Patients in whom the baseline recording of epidural MEPs produces noresponse have a higher risk of postoperative motor deficits than those with arecordable D wave [25]. It is not known whether this is due to an inherent sub-clinical damage and “vulnerability” of the motor tract, or to the fact that therewas no monitoring support for the surgery. The mechanism of an unrecordableD wave coinciding with intact motor status (and recordable muscle MEPs) isbelieved to be due to chronic or inherent preexisting damage to the corticospinaltract resulting in a desynchronization of the wave [31] (see also Chapter 2, Fig.2.11, page 41). It appears that patients with prior surgery, those with very exten-sive tumors, and particularly those with prior radiation therapy are in this group.

The intraoperative amplitude decrease of the D wave correlates with post-operative outcome. If the D wave is unchanged, there is no permanent postop-erative deficit. If it declines more than 50% of the baseline value or evendisappears, the patients are likely to have a permanent motor deficit [11, 25].



6.3 INTERPRETATION OF MUSCLE MEP DATA

The presence of muscle MEPs indicates that the functional integrity of the cor-ticospinal tract is intact in all instances. Occasionally, in patients with a mod-erate motor deficit, it may be difficult to obtain recordings from both lowerextremities. If that occurs, responses in the weaker leg usually require higherstimulation intensities. Intraoperative preservation of muscle MEPs meansintact motor function postoperatively in all cases. Intraoperative loss of muscleMEPs indicates some postoperative impairment of voluntary motor controlwith a high (∼90%) specificity. For instance, muscle MEPs lost in one leg duringthe resection mean that the patient will postoperatively be unable to move thisparticular extremity, at least for a limited period of time. We call this a “tem-porary motor deficit.” Loss of muscle MEPs in both legs obviously is indicativeof a bilateral motor deficit. Unilateral loss is of less concern because it has beenshown in the past that unilateral motor disruption always recovers through amechanism by which the intact side “takes over” control of the affected side[47]. These changes must be interpreted together with changes in D waveamplitude.

6.4 COMBINED INTERPRETATION OF D WAVE

AND MUSCLE MEP DATA [23, 27]

The D wave amplitude is a measure of the number of synchronized fast con-ducting fibers in the corticospinal tract. If 50% of these fibers are damaged bythe procedure, the amplitude will decrease to 50% of its baseline value.

From practical experience we know that the D wave decrease usually occursin small steps, going down 15%, 20%, 30%, and so forth. Most D wave ampli-tude decreases will coincide with a loss of muscle MEPs. It may be, however,that muscle MEP loss occurs without D wave amplitude decrease, or that the Dwave decreases without any changes in muscle MEPs. The underlying mecha-nisms of these observations are not understood at this time. In any event,preservation of the D wave above the 50% cutoff has been found to be predic-tive of long-term preservation (or recovery) of voluntary motor control. If thereis loss of muscle MEPs, with preserved D wave amplitude, a temporary motordeficit can be expected postoperatively. However, in this situation it is still safeto complete a resection, or to pause and wait for recordings to improve again(which they often do). This situation is the window of warning, the window ofreversible change, that allows for a change in surgical strategy before irreversibleinjury has occurred. This is the concept that the skeptical neurosurgeon muststudy before intraoperative MEP monitoring is dismissed as “useless.”



6.5 INFLUENCE OF MEP MONITORING

ON EXTENT OF RESECTION

In some cases, resection is terminated before the desired extent of resection isachieved because the acceptable limit of MEP change is reached. Although theactual number of cases is low (about 5% in the previously mentioned series[23]), this is an important factor in subsequent decision making. Dependingupon the actual extent of resection on the postoperative MRI scan and the his-tology of the lesion, a second stage of the resection may be attempted once thepatient has recovered motor control. This is of particular importance in patientswith spinal cord ependymomas, for whom complete tumor resection is essen-tial for long-term, progression-free, survival [48]. Among other criticisms, it hasbeen claimed that MEP monitoring may be too sensitive, actually stoppingresection too early [49]. Although a comparison inevitably must remain incom-plete, it appears from the available data that the extent of resection increasedsince monitoring began at our institution [50]. However, there may still be asignificant trade-off between extent of resection and preservation of motor func-tion in some cases. On the other hand, in an equally significant number of cases,stable recordings encouraged the surgeon to proceed with tumor resection eventhough the anatomical situation suggested otherwise.

6.6 OBSERVATIONS ON THE BEHAVIOR OF MEPS

DURING INTRAMEDULLARY SPINAL CORD

TUMOR SURGERY

Usually MEP changes occur toward the end of the resection. Since most spinalcord tumors are resected in an inside-out and piecemeal fashion (with theexception of some ependymomas), direct manipulation or vascular compro-mise occurs when the tumor-cord interface is reached. Often muscle MEPs dis-appear first. This may be preceded by an increase in threshold for this particularmuscle response. Pausing the resection and irrigating the cavity with warmsaline sometimes results in reappearance of the response. Similarly, some Dwave amplitude decrease may also be reversible by pausing and irrigating. If dis-section in a particular location results in MEP changes, the resection can oftenproceed at a different spot without further change. Sudden drops in D waveamplitude, often coinciding with sudden loss of muscle MEPs, is believed to beassociated with some vascular compromise rather than with direct physicalmanipulation of the nervous tissue. In some patients, temporary moderate ele-vation of mean blood pressure has been a successful means to improve theMEPs, with a satisfactory clinical result postoperatively.



In some situations the warning provided by intraoperative MEP changes isstill only of documentary value: whereas the removal of an astrocytoma can beterminated without jeopardizing the patient’s neurologic and oncologic out-come, the attempt to remove a hemangioblastoma is an all-or-none enterprise.The lesion has to be entirely removed, no matter what the MEP parametersindicate, or serious bleeding and/or swelling will lead to certain damage of thespinal cord. This, however, is a limitation imposed by the anatomic nature ofthe lesion, rather than a shortcoming of the monitoring technique.

Other important surgical observations concern the use of specific surgicalinstruments and their impact on changes in MEP recordings. For instance, itappears to be our own and the observation of others that the use of the ultra-sonic aspirator (CUSA, Valleylab, Boulder, Co) sometimes results in MEP dete-rioration. On the contrary, use of the Nd:YAG hand-held “contact” laser (SLT,Surgical Laser Technologies, Inc., Montgomery, PA) or special bipolars [51] tovaporize tumor and mobilize small fragments seems to be less damaging. Usinga bipolar coagulation always disrupts MEP recordings for the time the currentis active. One of the distinct advantages of the hand-held laser is that its usedoes not produce an electrical artifact, and therefore monitoring continuesundisturbed during its use.

7 ILLUSTRATIVE CASES

7.1 CASE 1

A 14-year-old girl presented with progressive dysesthesias in the left arm and legand a slight weakness of the left extremities. MRI disclosed an intramedullaryspinal cord tumor from C3 to C7 that turned out to be an astrocytoma.

During microsurgical gross total resection of the lesion, monitoring the Dwave (Fig. 4.2A) showed no change in its amplitude. Muscle MEPs in the ante-rior tibial muscles bilaterally showed preserved responses until the end ofsurgery (Fig. 4.2B). The MEP data indicated preserved functional integrity ofthe motor system. Postoperatively the motor status was unchanged.

7.2 CASE 2

A 9-year-old girl underwent resection of a cervicothoracic intramedullaryganglioglioma. There was no preoperative motor deficit. Toward the end ofthe procedure, when only a small amount of tumor tissue remained, a suddenloss of muscle MEPs in the right anterior tibial muscle occurred (Fig. 4.3A).Simultaneously a drop of the D wave amplitude of about 40% was noted



FIGURE 4.2 Preserved functional integrity of the motor pathways. Epidural (A) and muscle MEP(B) recordings of Case 1. Stable D wave amplitude and preserved muscle MEPs correlate with intactmotor control.

FIGURE 4.3 Temporary motor deficit. D wave amplitude decrease of 40% (B) and unilateral lossof muscle MEPs in the Right TA (A) correlate with monoplegia of the right leg immediately aftersurgery.



(Fig. 4.3B). The resection was terminated. Some residual tumor tissue liningthe cavity was left. Immediately after surgery the patient had a monoplegia ofthe right leg, as expected from the MEP data. Recovery started on the first post-operative day with some movements of the toes. After one week she hadregained antigravity muscle strength.

7.3 CASE 3

A 27-year-old woman underwent resection of a C5-Th1 ependymoma. Preop-eratively she had slight leg weakness. At baseline, muscle MEPs were presentin the right leg only (Fig. 4.4B). The absence of a muscle response in the otherleg indicated subclinical damage to the functional integrity of the motor tracts.Early in the dissection it became clear that, morphologically, the tumor hadextremely thinned the surrounding surviving cord tissue. However, stability ofthe epidural as well as the single side muscle MEP recording encouraged anattempt for tumor removal. The tumor was then entirely removed, and the Dwave amplitude decreased but remained above the 50% limit (Fig. 4.4A). Elic-iting the right leg muscle MEPs required a higher intensity and seven insteadof five stimuli per train. Nevertheless, they remained present. The postopera-tive clinical status was not significantly changed.

FIGURE 4.4 Continual recordings as reassurance of intact motor pathways in difficult surgicaldissection (case 3). The D wave amplitude (A) declined throughout the critical part of the proce-dure but not more than 50% of the baseline value. Muscle MEPs (B) were only present on one sideat the beginning of the procedure. The response was preserved until the tumor was completelyremoved. The patient had no significantly increased postoperative motor deficit.



7.4 CASE 4

A 3-year-old boy underwent a T4 to T11 laminotomy for resection of a thoraciclow-grade astrocytoma. Preoperatively he had a significant degree of scoliosisbut no neurological deficits. At baseline, there was no D wave because thetumor involved the cord almost all the way to the conus. Muscle MEPs wereonly recordable in the toe abductor muscles but not in the tibialis anterior mus-cles, indicating subclinical damage to the motor system. During resection, aftersome minor fluctuation of stimulus thresholds, a sudden loss of muscle MEPsoccurred after a bleeding tumor vessel was coagulated (Fig. 4.5A). The resec-tion was stopped, warm irrigation was applied to the resection bed, and theblood pressure was increased from 110/80 to about 140/95. After about 5 minthe MEPs reappeared in the toe abductor on the right side, albeit with a higherstimulus threshold (Fig. 4.5B). The patient started to move his right leg severalhours after the operation. Thus even poor recordings at the baseline provideuseful intraoperative information and correctly correlate with postoperativerecovery.

FIGURE 4.5 Monitoring difficulty. In Case 4 there was no D wave because of the caudal tumorlocation. In addition, only the abductor hallucis muscle responses (not the tibialis anteriorresponses) could be elicited, indicating either some subclinical motor damage or simply the resultof the patient’s young age (3 years). After coagulation of a tumor vessel, all muscle responsesabruptly disappeared (A). After irrigation and slight hypertension, they reappeared on the right side(B), but not reliably on the left. The patient started to move his right leg after several hours, andhis left leg on the sixth postoperative day.



8 SUMMARY

The combined intraoperative monitoring of D waves and muscle MEPs elicitedby transcranial electrical stimulation during intramedullary spinal cord tumoroperations is based on a firm neurophysiological concept, and its use is practi-cal and safe. Intraoperative MEP monitoring data correctly represent the clini-cal “reality” of the patient’s motor status: the presence of muscle MEPs alwaysindicates intact motor function. Intraoperative loss of muscle MEPs indicates atemporary loss of motor function in the corresponding limb as long as the Dwave amplitude remains above 50% of the baseline value. Further decline of theamplitude indicates permanent paraplegia or, in the case of a high cervicaltumor, quadriplegia.

The technique is readily implemented in a routine neurosurgical environ-ment. It allows for the identification of impairment of the functional integrityof the motor pathways before a permanent deficit occurs. This knowledge hasproven to be extremely valuable for intraoperative decision making.

Included with the accompanying CD are two videos (choose Chapter 4 fromthe accompanying CD main menu). The first video shows a small clip of theCUSA being used to debulk a medullary tumor. The second video shows theloss of the right toe abductor MEPs during coagulation of blood vessels forhemostasis after tumor removal.

ACKNOWLEDGMENTS

The author is indebted to San-San Chiang, Linda Velazquez, Ingrid Kothbauer-Margreiter, Matevz Krzan, Nobu Morota, Shlomo Constantini, George I. Jallo,Fred J. Epstein, and Vedran Deletis.

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C H A P T E R 5

Selective Spinal CordLesioning Proceduresfor Spasticity and PainMARC SINDOU AND PATRICK MERTENS

Department of Neurosurgery, Hopital Neurologique Pierre Wertheimer,University of Lyon, Lyon, France

Part I: Selective Lesioning Procedures in Spinal Rootsand Spinal Cord for Treatment of Spasticity

1 Procedures1.1 Posterior Rhizotomies1.2 Results of Posterior Rhizotomies1.3 Longitudinal Myelotomy1.4 Surgery in the Dorsal Root Entry Zone (DREZ)

2 Indications2.1 Indications for Surgery in Adults2.2 Indications for Surgery in Children

with Cerebral Palsy3 ConclusionPart II: Selective Spinal Cord Lesioning Procedures

for Treatment of Pain: DREZ Lesions1 Microsurgical DREZotomy

1.1 Operative Procedure at the Cervical Level1.2 Operative Procedure at the Lumbosacral Level1.3 Neurophysiological Monitoring as an Aid to Surgery1.4 Microelectrophysiology and Microdialysis

Studies in the Dorsal Horn During Surgery2 Radiofrequency (RF) Thermocoagulation Procedure3 DREZ Procedures with the Laser Beam4 Ultrasonic DREZ Procedure5 Indications for DREZReferences



94 Marc Sindou and Patrick Mertens

Part I: Selective Lesioning Procedures in SpinalRoots and Spinal Cord for Treatment of Spasticity

ABSTRACT

Spasticity is one of the most common sequels of neurologic diseases. In mostpatients, spasticity is useful in compensating for lost motor strength. However, in asignificant number of patients it may become harmful and lead to further functionallosses. When not controllable by physical therapy and medications, excessive spas-ticity can benefit from neurostimulation, intrathecal Baclofen pharmacotherapy, bot-ulinum toxin injections, or selective ablative surgical procedures. Lesioning can beperformed at the level of the peripheral nerves, spinal roots, spinal cord, or the dorsalroot entry zone (DREZ). In this chapter, only selective procedures in the spinal roots,spinal cord, and DREZ will be described.

1 PROCEDURES

1.1 POSTERIOR RHIZOTOMIES

After Sherrington demonstrated in 1898 that decerebrate rigidity in an animalmodel was abolished by section of the dorsal roots (that is, by interruption ofthe afferent input to the monosynaptic stretch and polysynaptic withdrawalreflexes), posterior rhizotomy for the modification of spasticity was first per-formed by Foerster in 1908 [1]. Its undesired effects on sensory and sphincterfunction have limited its application in the past. To minimize these disadvan-tages, several authors in the 1960s and 1970s attempted to develop more selec-tive operations, especially for the treatment of children with cerebral palsy.

1.1.1 Posterior Selective Rhizotomy

To reduce the sensory side-effects of the original Foerster method, Gros andcoworkers [2] introduced a technical modification that consisted of sparing onerootlet of the five of each root, from L1 to S1. On similar principles, Ouaknine[3], a pupil of Gros, developed a microsurgical technique that consisted ofresecting one third to two thirds of each group of rootlets of all the posteriorroots from L1 to S1.

1.1.2 Sectorial Posterior Rhizotomy

In an attempt to reduce the side-effects of rhizotomy on postural tone in ambu-latory patients, Gros [4] and his pupils Privat [5] and Frerebeau [6] proposeda topographic selection of the rootlets to be sectioned. First, a preoperative


Selective Spinal Cord Lesioning Procedures for Pain and Spasticity 95

assessment of spasticity useful for postural tone (abdominal muscles, quadri-ceps, gluteus medius) and spasticity harmful to the patient (hip flexors, adduc-tors, hamstrings, and triceps surae) is conducted. Mapping of the evoked motoractivity of the exposed rootlets, from L1 to S2, by direct electrostimulation ofeach posterior group of rootlets is then carried out, and the rootlets to be sec-tioned are determined according to the preoperative program.

1.1.3 Partial Posterior Rhizotomy

Fraioli and Guidetti [7] reported on a procedure by which the dorsal half ofeach rootlet of the selected posterior roots is divided a few millimeters beforeits entrance into the posterolateral sulcus. The authors report good results with-out significant sensory deficit, the latter being explained by the fact that partialsection leaves intact a large number of fibers of all types.

1.1.4 Functional Posterior Rhizotomy

The search for specially organized circuits responsible for spasticity led Fasanoand associates [8] to propose a new method called functional posterior rhizo-tomy. This method is based on bipolar intraoperative stimulation of the poste-rior rootlets and analysis of different types of EMG reflex responses. Responsescharacterized by a permanent tonic contraction, an after-discharge pattern, ora large spatial diffusion to distant muscle groups were considered to belong todisinhibited spinal circuits responsible for spasticity. Functional posteriorrhizotomy—which was especially conceived for children with cerebral palsy—has also been used by other outstanding surgical teams, each one havingbrought its own technical modifications to the method [9–12]. Our personaladaptation of these methods is illustrated in Fig. 5.1.

1.2 RESULTS OF POSTERIOR RHIZOTOMIES

The results of posterior rhizotomies in children with cerebral palsy—whateverthe technical modality may be—have been recently reported in several publi-cations. We have reviewed and quoted them (46 references) on the occasion ofthe report of our own series [13]. Briefly, these publications show that about75% of the patients had nearly normal muscle tone at 1 year or more aftersurgery without spasticity limiting the residual voluntary movements of thelimbs. After a serious and persisting physical therapy and rehabilitation pro-gram, most children demonstrated improved stability in sitting and/or increasedefficiency in walking. It must be noted, however, that preexisting orthopedicdeformities cannot be improved with this method [13].


96

FIGURE 5.1 Lumbosacral posterior rhizotomy for children with cerebral palsy. Our personal technique consists of performing a limited osteoplasticlaminotomy using a power saw, in one single piece, from T11 to L1 (left). The laminae will be replaced at the end of the procedure and fixed with wires(right). The dorsal (and ventral) L1, L2, and L3 roots are identified by means of the muscular responses evoked by electrical stimulation performed intradu-rally just before entry into their dural sheaths. The dorsal sacral rootlets are recognized at their entrance into the dorsolateral sulcus of the conusmedullaris. The landmark between S1 and S2 medullary segments is located approximately 30 mm from the exit of the tiny coccygeal root from the conus.The dorsal rootlets of S1, L5, and L4 are identified by their evoked motor responses. The sensory roots for bladder (S2–S3) can be identified by monitor-ing vesical pressure. Those for the anal sphincter (S3–S4) can be identified by rectomanometry (or simply using finger introduced into the patient’s rectum)or EMG recordings. Surface spinal cord SEP recordings from tibial nerve (L5–S1) and pudendal nerve (S1–S3) stimulation may also be helpful.

For the surgery to be effective, a total amount of 60% of dorsal rootlets must be cut (with a different amount of rootlets cut according to the level andfunction of the roots involved). Also, the correspondence of the roots with the muscles having harmful spasticity or useful postural tone must be con-sidered in determining the amount of rootlets to be cut; in most cases, L4 (which predominantly gives innervation to the quadriceps femoris) has to bepreserved.



1.3 LONGITUDINAL MYELOTOMY

Longitudinal myelotomy, which was introduced by Bischof [14], was mademore selective by Pourpre [15] and later on by Laitinen [16]. The method con-sists of a frontal separation between the posterior and anterior horns of thelumbosacral enlargement from T11 to S2 performed from inside the spinalcord after a posterior commisural incision that reaches the ependymal canal.In Laitinen’s series of 25 patients, 60% had complete relief of spasticity and 36%showed some residual spasticity in one or both legs. Within 1 year, some mus-cular tone returned in most patients but seldom produced troublesome spas-ticity. A harmful effect on bladder function was present in 27% of the patients.Longitudinal myelotomy is indicated only for spastic paraplegias with flexionspasms, when the patient has no residual useful motor control and no bladderand sexual function.

1.4 SURGERY IN THE DORSAL ROOT ENTRY

ZONE (DREZ)

Selective posterior rhizotomy in the dorsal root entry zone (DREZ), referred toas micro-DREZotomy (MDT), was introduced in 1972 [17] to treat intractablepain. Because of its inhibitory effects on muscular tone, it has been applied topatients with focalized hyperspasticity [18–21]. This method attempts to selec-tively interrupt the small nociceptive and the large myotatic fibers (situated lat-erally and centrally, respectively), while sparing the large lemniscal fibers whichare regrouped medially. It also enhances the inhibitory mechanisms of Lissauer’stract and the dorsal horn [22] (Fig. 5.2 left).

MDT, the technique of which has been described elsewhere [23–25], con-sists of microsurgical incisions that are 2 to 3 mm deep and at a 35° angle forthe cervical level (Fig. 5.2 right) and at a 45° angle for the lumbosacral level(Fig. 5.3), followed by bipolar coagulations performed ventrolaterally at theentrance of the rootlets into the dorsolateral sulcus, along all the cord seg-ments selected for operation. For patients with paraplegia [24], the L2–S5segments are approached through a T11-L2 laminectomy, whereas for thehemiplegic upper limb [25], a C4–C7 hemilaminectomy with conservation ofthe spinous processes is sufficient to reach the C5–T1 segments. Identificationof the cord levels related to the undesirable spastic mechanisms is achievedby studying the muscle responses to bipolar electrical stimulation of the ante-rior and/or posterior roots. The motor threshold for stimulation of anteriorroots is one third that of the threshold for posterior roots. Then, the lateralaspect of the DREZ is exposed so that the microsurgical lesioning can be per-formed. Lesions are 2 to 3 mm in depth and are placed at 35 to 45° angles in the


FIGURE 5.2 Micro-DREZotomy (MDT). Left, organization of fibers at the DREZ in humans. Thelarge arrow shows the proposed extent of the MDT affecting the lateral and central bundles formedby the nociceptive and myotatic fibers, as well as the excitatory medial part of the Lissauer Tractand the upper layers of the dorsal horn. Right, principle behind the MDT technique. Example of theMDT at the cervical level through a right cervical hemilaminectomy (the procedure for the lumbosacralroots is the same). The right C6 posterior root has been retracted toward the inside to make theventrolateral region of the DREZ accessible. The incision is performed into the dorsolateral sulcususing a small piece of razor blade (upper operative view). The incision is 2 to 3 mm deep and ismade at a 35° angle (at a 45° angle for the lumbosacral level). Then microcoagulations are createdwith a very sharp and graduated bipolar microforceps down to the apex of the dorsal horn (loweroperative view).



FIGURE 5.3 MDT technique at the lumbosacral level. Top left, exposure of the conus medullaris through a T11–L1 laminectomy. Bottom left, approachof the left dorsolateral sulcus. For this approach, the rootlets of the selected lumbosacral dorsal roots are displaced dorsally and medially to obtain properaccess to the ventrolateral aspect of the DREZ. Right, the rootlets of the selected dorsal roots are retracted dorsomedially. They are subsequently held witha specially designed ball-tip microsucker, used as a small hook to gain access to the ventrolateral part of the DREZ. After the fine arachnoidal filamentssticking the rootlets together with the pia mater are divided with curved sharp microscissors (B), the main arteries running along the dorsolateral sulcusare dissected and preserved, while the smaller ones are coagulated with a sharp bipolar microforceps (F). Then, a continuous incision is performed using amicroknife (K) made with a small piece of razor blade inserted within the striated jaws of a curved razor blade holder (K). The cut is—on average—ata 45° angle and to a depth of 2 mm. The surgical lesion is completed by doing microcoagulations under direct magnified vision, at a low intensity, insidethe posterolateral sulcomyelotomy down to the apex of the dorsal horn. These microcoagulations are made by means of the special sharp bipolar forceps(F), insulated except for 5 mm at the tips and graduated every millimeter.

99



ventrolateral aspect of the sulcus all along the selected segments of the spinalcord. Intraoperative neurophysiological monitoring may be of some help foridentifying cord levels, quantifying the extent of MDT, and avoiding impairinglong fiber tracts.

MDT is indicated in paraplegic patients, especially when they are bedriddenas a result of disabling flexion spasms, and in hemiplegic patients with irre-ducible and/or painful hyperspasticity in the upper limb [23–27]. MDT also canbe used to treat neurogenic bladder with uninhibited detrusor contractionsresulting in leakage of urine around a catheter [26].

To date, our series has consisted of 45 patients with unilateral cervical(C5–T1) MDT for harmful spasticity in the upper limb, 121 patients with bilat-eral lumbosacral MDT (L2–S1 or S5) for disabling spasticity in the lower limbs,and 12 patients with bilateral sacral S2–S3 (S4) MDT for hyperactive neurogenicbladder only. Effects on muscular tone can be judged only after a 3-monthfollow-up. A “useful” effect on spasticity, allowing withdrawal of antispasmodicmedications, was obtained in 78% of the patients with a spastic upper limb. Asimilarly useful effect was obtained in 75% of the patients with spasticity in thelower limbs. When spasms were present in paraplegic patients, they were sup-pressed or markedly decreased in 88% of the patients. When compared topatients with multiple sclerosis (75% with good results), the results were betterin patients with spasticity (and spasms) caused by pure spinal cord lesions (80%with good results). The least improvement was observed in patients with spas-ticity resulting from cerebral lesions (60% with good results). Reduction inspasticity usually leads to a significant improvement in abnormal postures andarticular limitations. This was achieved in about 90% of our patients.

For the hemiplegic upper limb, the increase in articular amplitude was mostremarkable for the elbow and shoulder (when not “frozen”) and much morelimited for the wrist and fingers, especially if there was retraction of the flexormuscles and no residual voluntary motor activity in the extensors. For the lowerlimb(s), with abnormal postures in flexion, the increase in amplitude of jointmovement was very much dependent on the degree of the preoperative retrac-tions. When the post-MDT gains were deemed insufficient because of persistentjoint limitations, complementary orthopedic surgery was indicated. Withregard to the patients (n = 5) who had paraplegia with irreducible hyperexten-sion, all were completely relieved. In the patients with some voluntary move-ments hidden behind spasticity, reduction in the hypertonia resulted in animprovement in voluntary motor activity. Fifty percent of the patients operatedon for spasticity in the upper limb had better motor activity of the shoulder andarm, but only half of those with some preoperative distal motor functionobtained additional hand prehension. Only 10% of the patients with spasticityin the lower limb(s) had significant motor improvement after surgery (becausemost patients in this group had no preoperative motor function). In these



severely affected patients, the main benefit was better comfort, less pain, abil-ity to resume physical therapy, and less dependence in daily life (see [27] forpre- and postoperative assessment of patients, with details on the functionalscores used). Bladder capacity was significantly improved in 85% of the 38 patientswho had a hyperactive neurogenic bladder with urine leakage around thecatheter. The 32 patients who improved were those in whom the detrusor wasnot irreversibly fibrotic. Pain, when present, was in general favorably influ-enced. MDT continually produced a marked decrease in sensation.

Because most patients were in a precarious general and neurological state,death occurred in 5 patients (4%), resulting from respiratory problems in 4 andbed sores in 1. Two patients with multiple sclerosis (MS) presented with acutebut transient increases in their preexisting neurological symptoms during thepostoperative period. Two others had a new postoperative clinical manifesta-tion of the disease. The last of the complications we have to mention concernsa patient who was operated on at the cervical level and had a persistent motordeficit in the ipsilateral leg after surgery.

With rigorous selection of patients, MDT can be very effective in relievingpain and suppressing excessive spasticity. Good long-lasting relief of excessspasticity was achieved in 80% of our patients. As a result, MDT, sometimescombined with complementary orthopedic surgery, resulted in significantimprovement in patient comfort and joint deformities, and even enhancementof residual voluntary motility hidden preoperatively behind hypertonicity.

2 INDICATIONS

2.1 INDICATIONS FOR SURGERY IN ADULTS

2.1.1 Spinal Cord Stimulation

Provided that the spasticity is mild and the dorsal columns are still functioning,spinal cord stimulation can be useful for treating spasticity from diseases affect-ing the spinal cord (e.g., MS or degenerative diseases such as Strumpell-Lorrainsyndrome). A percutaneous trial before a definitive implantation may be useful.

2.1.2 Intrathecal Baclofen

Intrathecal baclofen administration is indicated for para- or tetraplegic patientswith severe and diffuse spasticity, especially when spasticity has a spinal origin.Because of its reversibility, this method should be used before an ablative proce-dure is considered. But the range between excessive hypotonia with loss of strengthand an insufficient effect is very narrow. An intrathecal test through a temporaryaccess port can be useful when deciding if permanent implantation is indicated.



2.1.3 Neuroablative Techniques

Neuroablative techniques are indicated for severe focalized spasticity in thelimbs of paraplegic, tetraplegic, or hemiplegic patients. Neurotomies are pre-ferred when spasticity is localized to muscle groups innervated by a smallnumber of, or a single, peripheral nerve (or nerves). When spasticity affects anentire limb, MDT is preferred. Several types of neuroablative procedures can becombined in the treatment of one patient, if needed.

Whatever the situation and the etiology may be, orthopedic surgery shouldbe considered only after spasticity has been reduced by physical and pharma-cological treatments first and, when necessary, by neurosurgical procedures.

Guidelines for surgical indications have been detailed elsewhere [28, 29]and are summarized in Fig. 5.4. The general rule is to tailor individual treat-ments as much as possible to the patient’s particular problems.

2.2 INDICATIONS FOR SURGERY IN CHILDREN

WITH CEREBRAL PALSY

Surgical indications depend on preoperative abilities, disabilities, and the even-tual functional goals. As a means of guidance, we have adopted the six-groupclassification as defined by Abbott [30].

FIGURE 5.4 Decision-making for hyperspasticity in adults.



2.2.1 Independent Ambulatory Patients

In independent ambulatory patients, the goal is to improve efficiency and cosmet-ics in walking by eliminating as many abnormally responsive neural circuits as canbe identified through functional posterior rhizotomy. Surgery is best performed assoon as possible after the child has demonstrated the ability to work with a thera-pist, usually between ages 3 and 7 years, and frequently must be done in conjunc-tion with operations on tendons because of concomitant shortened muscles.

2.2.2 Ambulatory Patients Dependent on Assistance Devices

For ambulatory patients dependent on assistance devices (canes, crutches, rol-lators, walkers), the goal is to lessen that dependence. A child with poor trunkcontrol or lack of protective reaction but with good underlying strength in theantigravity muscles can safely undergo a functional posterior rhizotomy. Inchildren dependent on hypertonicity in the quadriceps to bear weight, a limitedsectorial rhizotomy is preferable. For children who are in the process of devel-oping ambulatory skill and need a temporary assistance device, it is importantto delay surgery until they have perfected these skills.

2.2.3 Quadruped Crawlers

For quadruped crawlers (or bunny hoppers) the goal is to achieve assistedambulation during mid-childhood to early adolescence. A functional posteriorrhizotomy will decrease hypertonicity in the leg musculature and allow betterlimb alignment in the standing position for a child with adequate muscularstrength. However, a child who exhibits quadriceps weakness can be consideredfor a sectorial posterior rhizotomy. Children in this group can present at ayoung age with progressive hip dislocation. The goal is to stop the progressiveorthopedic deformity by using obturator neurotomy with adductor tenotomiesor functional posterior rhizotomy.

2.2.4 Commando (or Belly) Crawlers

For commando (or belly) crawlers disabled by severe deficiencies in the pos-tural control, the goal of posterior rhizotomy is only to improve functioning inthe sitting position by increasing stability.

2.2.5 Totally Dependent Children

In totally dependent children with no locomotive abilities, the goals are tosimply improve comfort and facilitate care. As with group 4 (commando [orbelly] crawlers), the preferred treatment is posterior rhizotomy, but there is alsoa need for exploring the efficacy of intrathecal baclofen.



2.2.6 Children with Asymmetrical Spasticity

For asymmetrical spasticity, selective peripheral neurotomies must be consid-ered, especially obturator and tibial for a spastic hip or foot, respectively. Forupper limb spasticity, the MDT procedure and/or selective neurotomies of theflexor muscles of wrist and fingers can be considered.

3 CONCLUSION

Spasticity is usually a useful substitute for deficiencies in motor strength. There-fore, it must be preserved. Although it happens infrequently, it can lead to theharmful aggravation of a motor disability. When excessive spasticity is not suffi-ciently controlled by physical therapy and pharmacological agents, patients canconsider surgery, especially neurosurgical procedures. By suppressing excessivespasticity, correcting abnormal postures, and relieving the frequently associatedpain, surgery for spasticity allows physiotherapy to be resumed and sometimesresults in the reappearance of, or improvement in, useful voluntary motility.When dealing with these patients, the surgeon must know the risks of the avail-able treatments. To minimize those risks, the surgeon needs a strong anatomic,physiological, and chemical background, rigorous methods to assess and quan-tify the disorders, and the ability to work in a multidisciplinary team [29].

Part II: Selective Spinal Cord LesioningProcedures for Treatment of Pain:DREZ Lesions

ABSTRACT

In the 1960s, a large number of neurophysiologic investigations proved that thedorsal horn was the primary level of modulation of pain sensation. This idea waspopularized in 1965 through the gate control theory [31], which drew neurosur-geons’ attention to this area as a possible target for pain surgery. Neurostimulationof the primary afferent neurons was developed to enhance the inhibitory mecha-nisms of the spinal cord [32]. Conversely, in 1972 we undertook anatomical studiesand preliminary surgical trials in the human dorsal root entry zone (DREZ) todetermine whether a destructive procedure at this level was feasible [33, 34]. Soonafter, in 1974, Nashold and his group started to develop DREZ lesions using the RF-thermocoagulation as the lesion maker in the substantia gelatinosa of the dorsal horn[35] and later in the whole DREZ [36]. This has been performed especially for paincaused by brachial plexus avulsion. Later on, DREZ procedures were performed byusing a laser [37, 38] and an ultrasound probe [39, 40] for pain caused by brachialplexus avulsion.



1 MICROSURGICAL DREZotomy

This procedure consists of a longitudinal incision of the dorsolateral sulcusventrolaterally at the entrance of the rootlets into the sulcus. Microbipolarcoagulations are performed continuously inside the sulcus down to the apex ofthe dorsal horn and along all the spinal cord segments selected for surgery. Thelesion, which penetrates the lateral part of the DREZ and the medial part of thetract of Lissauer (TL), extends down to the apex of the dorsal horn, which canbe recognized by its brown-gray color. The average lesion is 2 to 3 mm deep andis made at a 35° angle medially and ventrally.

The procedure is presumed to preferentially destroy the nociceptive fibersgrouped in the lateral bundle of the dorsal rootlets, as well as the excitatorymedial part of the TL. The upper layers of the dorsal horn are also destroyed ifmicrobipolar coagulations are made inside the dorsal horn . The upper layers ofthe dorsal horn are known to be the site of “hyperactive” neurons, especially inthe cases with peripheral deafferentation (Fig. 5.5). The procedure is presumedto at least partially preserve the inhibitory structures of the DREZ, (i.e., the lem-niscal fibers reaching the dorsal column, as well as their recurrent collateralsto the dorsal horn and the substantia gelatinosa [SG] propriospinal inter-connecting fibers running through the lateral part of the TL). This MDT was

FIGURE 5.5 Dorsal horn microelectrode recordings in man. The electrode was a floating tung-sten microelectrode that was implanted intraoperatively free-hand under the operative microscope;it reached 5 mm in depth (in laminae IV–VI). The vertical bars are 50 µV, and the horizontal barsare 100 ms. Upper trace, normal activity. Recordings in a nondeafferented dorsal horn (spasticpatient). Left, almost no spontaneous activity (3 spikes at random). Middle, spike burst discharges(arrows) evoked by regular light tactile stimulation of the corresponding dermatoma. Right, elec-trical stimulation of the corresponding peripheral nerve. Lower trace, deafferentation hyperactiv-ity. Recordings in the L5 cord segment of a patient with pain caused by a traumatic section of thehemi-cauda equina from root L4 to S4. Left, spontaneous activity of the recorded unit: continuous,regular, high-frequency discharge. Middle, unit during light tactile stimulation of the L4–S1 der-matome (arrow). Right, during electrical stimulation of the tibial nerve (the arrows are two con-secutive stimuli). Note the continuous regular discharges, which remain unaltered.



conceived in order to prevent the complete abolition of tactile and propriocep-tive sensations and to avoid deafferentation phenomena [41].

Working in the DREZ requires knowledge of the morphological anatomyof the dorsal roots corresponding to the spinal level. Details have been givenin previous publications [42–45]. The axis of the dorsal horn in relation tothe sagittal plan crossing the dorsolateral sulcus will condition the angula-tion of the DREZotomy. According to 82 measurements performed by Young(personal communication, 1991), the mean DREZ angle is 30° at C6, 26° atT4, 37° at T12, and 36° at L3. The site and extent of the DREZ lesion willalso be determined by the shape, width, and depth of the TL and dorsal horn(Fig. 5.6).

Surgery is performed with the patient under general anesthesia, but withonly an initial short-lasting muscle relaxant to allow intraoperative observa-tion of motor responses to bipolar electrical stimulation of the nerve roots.Stimulated ventral roots have a motor threshold at least three times lower thanthe dorsal roots. Standard microsurgical techniques are used with 10× to 25×magnification.

1.1 OPERATIVE PROCEDURE AT THE CERVICAL LEVEL

The prone position with the head and neck flexed in the “concorde” positionhas the advantage of avoiding brain collapse caused by cerebral spinal fluid(CSF) depletion. The head is fixed with a three-pin head holder. The level oflaminectomy is determined after identification of the prominent spinousprocess of C2 by palpation. A hemilaminectomy, generally from C4 to C7, withpreservation of the spinous processes, allows sufficient exposure to the pos-terolateral aspect of the cervical spinal cord segments that correspond to theupper limb innervation, that is, the rootlets of C5 to T1 (T2).

After the dura and the arachnoid are opened longitudinally, the exposedroots and rootlets are dissected free by separation of the tiny arachnoid fila-ments that bind them to each other, to the arachnoid sheath, and to the spinalcord pia mater. The radicular vessels are preserved.

Each ventral and dorsal root from C4 to T1 is electrically stimulated at thelevel of its corresponding foramen to precisely identify its muscular innervationand its functional value. Responses are in the diaphragm for C4 (the responseis palpable below the lower ribs), in the shoulder abductors for C5, in the elbowflexors for C6, in the elbow and wrist extensors for C7, and in the muscles ofthe hand for C8 and T1.

Microsurgical lesions are performed at selected levels that correspond to thepain territory. The technique is summarized and illustrated in Fig. 5.2 of the



previous chapter. The incision is made with a microknife. Then microcoagula-tions are made in a “chain” (i.e., dotted) manner. Each microcoagulation is per-formed by short-duration (a few seconds), low-intensity, bipolar electrocoagula-tion with a special sharp bipolar forceps. The depth and extent of the lesion

FIGURE 5.6 Variations of shape, width, and depth of the DREZ area, according to the spinal cordlevel (from top to bottom: cervical n° 7, thoracic n° 5, lumbar n° 4, sacral n° 3). Note how, at thethoracic level, Lissauer’s tract is narrow and the dorsal horn deep. Therefore, it is easy to under-stand that DREZ lesions at this level can be dangerous for the corticospinal tract and the dorsalcolumn.



depend on the degree of the desired therapeutic effect and the preoperative sen-sory status of the patient.

If the laxity of the root is sufficient, the sulcotomy is accomplished throughan incision performed continuously in the dorsolateral sulcus, ventrolaterallyalong all of the rootlets of the targeted root. If this is not the case, a partial ven-trolateral section is made successively on each rootlet of the root after the sur-geon has isolated each one by separation of the tiny arachnoid membranes thathold them together.

For pain due to brachial plexus avulsion, dotted microcoagulations insidethe dorsal horn (at least 3 mm in depth from the surface of the cord) are per-formed after incision of the dorsolateral sulcus. Sharp graduated bipolar forcepsare used to make the microcoagulations at the level of the avulsed roots. Selec-tive ventrolateral DREZ lesions are extended to the root remaining above andbelow. In brachial plexus avulsion, dissection of the spinal cord is sometimesdifficult to achieve safely because of scar tissue adhering to the cord. Atrophyand/or gliotic changes at the level of the avulsed roots can make identificationof the dorsolateral sulcus hazardous. In such cases, it is necessary to start fromthe roots remaining above and below. The presence of tiny radicular vessels thatenter the cord may help determine the site of the sulcus. Yellow areas corre-sponding to old hemorrhages on the surface of the cord and/or microcavities inthe depth of the sulcus and the dorsal horn provide some guidance for tracingthe sulcomyelotomy. When the dorsolateral sulcus is difficult to find, intraop-erative monitoring of the dorsal column somatosensory evoked potentials(SEPs) evoked by stimulation of the tibial nerve is especially helpful.

1.2 OPERATIVE PROCEDURE AT THE

LUMBOSACRAL LEVEL

The patient is positioned prone on thoracic and iliac supports, and the head isplaced 20 cm lower than the level of the surgical wound to minimize the intra-operative loss of CSF. The desired vertebral level is identified by palpation ofthe spinous processes or, if this is difficult, by a lateral x-ray study that includesthe S1 vertebra. Interspinous levels identified by a needle can then be markedwith methylene blue. A laminectomy—either bilateral or unilateral, accordingto pain topography—from T11 to L1 (or L2) is performed. The dura and arach-noid are opened longitudinally and the filum terminale is isolated. Roots arethen identified by electrical stimulation.

The L1 and L2 roots are easily identified at their penetration into theirrespective dural sheaths. Stimulation of L2 produces a response of the iliopsoasand adductor muscles.



Identification of L3 to L5 is difficult for many reasons: (1) the exit throughtheir respective dural sheaths is caudal to the exposure; (2) the dorsal rootletsenter the DREZ along an uninterrupted line; (3) the ventral roots are hidden infront of the dentate ligament; and (4) the motor responses in the leg to stimu-lation of the roots are difficult to observe intraoperatively because of the patient’sprone position. Stimulation of L3 produces a preferential response in the adduc-tors and quadriceps, of L4 in quadriceps, and of L5 in the tibialis anteriormuscle.

Stimulation of the S1 dorsal root produces a motor response of the gastroc-nemius-soleus group that can be confirmed later by repeatedly checking theAchilles ankle reflex before, during, and after MDT at this level.

Stimulation of the S2–S4 dorsal roots (or better, the corresponding spinalcord segments directly) can be assessed by recording the motor vesical or analresponse by use of cystomanometry, rectomanometry, or electromyography ofthe anal sphincter (or by inserting a finger into the rectum). Because neuro-physiological investigations are time-consuming to perform in the operatingroom, we have found that measurements at the conus medullaris can be suffi-cient in patients who already have severe preoperative impairment of their vesi-coanal functions. These measurements, based on human postmortemanatomical studies, have shown that the landmark between the S1 and S2 seg-ments is situated around 30 mm above the exit from the conus of the tiny coc-cygeal root.

Microsurgical DREZotomy at the lumbosacral levels follows the same prin-ciples as at the cervical level. The technique is summarized and illustrated inFig. 5.3 of the previous chapter.

At the lumbosacral level, MDT is difficult and possibly dangerous because ofthe rich vasculature of the conus. The posterolateral spinal artery courses alongthe posterolateral sulcus. Its diameter is between 0.1 and 0.5 mm, and it is fedby the posterior radicular arteries. It joins caudally with the descending ante-rior branch of the Adamkiewicz artery through the conus medullaris anasto-motic loop of Lazorthes. If it is freed from the sulcus, this artery can bepreserved.

1.3 NEUROPHYSIOLOGICAL MONITORING AS AN AID

TO SURGERY [46–48]

Intraoperative monitoring of SEPs can be performed at the surface of theexposed spinal cord. Recordings of presynaptic potentials from the dorsal rootand postsynaptic potentials from the dorsal horn can be useful for identificationof the spinal cord segments. Potentials have a maximal amplitude in C6–C7stimulation of the median nerve and the C8 segment for stimulation of the



ulnar nerve. They have a maximum amplitude in the L5–S2 segments for stim-ulation of the tibial nerve, and in the S2–S4 segments for stimulation of thedorsal nerve of the penis or clitoris (see Chapter 9).

Recordings of surface spinal cord SEPs can also be helpful in monitoring thesurgical lesion itself. Dorsal column potentials can be monitored to check theintegrity of the ascending dorsal column fibers, especially when the dorsolateralsulcus is not clearly marked (as is common in brachial root avulsion). The dorsalhorn potentials can be monitored to follow the extent of MDT, particularly whengood sensory functions are present before surgery (see legend of Fig. 5.7).

1.4 MICROELECTROPHYSIOLOGY

AND MICRODIALYSIS STUDIES IN THE DORSAL

HORN DURING SURGERY

Unitary spikes generated in the dorsal horn neurons are interesting to recordduring DREZotomy to indicate abnormal activities, to help identify the surgi-cal target, and to better understand the electrophysiological mechanisms under-lying painful phenomena. Toward this goal, our group in Lyon has developed

FIGURE 5.7 Effects of MDT on the evoked electrospinogram (EESG). Recordings from the sur-face of the dorsal column, medially to the DREZ at the C7 cervical (Ce) and the L5 lumbosacral(LS) segments, ipsilateral to the stimulation of the median and the tibial nerve, respectively, before(A) and after (B) MDT. The initial positive event P9 (for cervical) (P17 for lumbosacral) corre-sponds to the far-field compound potential originating in the proximal part of the brachial (lum-bosacral) plexus. The small and sharp negative peaks N11 (N21) correspond to near-field presynapticsuccessive axonal events, probably generated in the proximal portion of the dorsal root, the dorsalfuniculus, and the large-diameter afferent collaterals to the dorsal horn. After MDT, all of thesepresynaptic potentials remain unchanged. The larger slow negative wave N13 (N24) correspondsto the postsynaptic activation of the dorsal horn by group I and II peripheral afferent fibers of themedian (tibial) nerves. They are diminished after MDT (in the order of two thirds). The later neg-ative slow wave N2 (just visible in the cervical recording) corresponds to postsynaptic dorsal hornactivity consecutive to the activation of group II and III afferent fibers. N2 is suppressed after MDT(Reprinted from [46]).



special, simplified floating microelectrodes. At the beginning, these electrodeswere based on the design by Merril and Ainsworth [49], and later they weredeveloped into an original design (i.e., a double microelectrode with anenhanced ability to distinguish spikes from artifacts [50]). In this way, we haveconducted recordings in 25 patients. To learn about specific patterns recordedfrom deafferented neurons, more patients must be studied.

With approval from our Ethical Committee, our group has performedmicrodialysis studies in the dorsal horn of patients undergoing DREZotomy[51]. The aim of the work was to measure concentrations of some of the mainneurotransmitters hypothesized from the animal experiments to be present inthe human dorsal horn. The microprobe has an apical 4-mm-long tubularmembrane [diameter: 0.216 mm, Cuprophane (HOSPAL Industrie, Meyzieu,France), cutoff 6000 Da]. The probe is perfused at 2 µl/min with a Ringer solu-tion. Dialysate fractions are collected from the extracellular fluid every 5 minfor about 1 hr. All the samples are frozen for later analysis [high performanceliquid chromatography (HPLC) with fluometric detection]. At the present timewe have made the technique feasible for identification and dosages of the fol-lowing substances: glutamate, aspartate, GABA, glycine, taurine, serine, andthreonine.

The preliminary results indicate some differences between painful and non-painful states. Further studies are needed before we can give conclusions.

2 RADIOFREQUENCY (RF)THERMOCOAGULATION PROCEDURE

In 1976 Nashold and his group published data on a method using RF thermo-coagulation to destroy hyperactive neurons in the substantia gelatinosa [35]and in 1979 in the whole DREZ region [36]. In 1981 [52] the technique wasmodified to produce less extensive lesioning so that the risk of encroachmentinto the neighboring corticospinal tract and dorsal column would be mini-mized. With the modified technique, the lesion is made with a 0.5 mm insu-lated stainless steel electrode with a tapered noninsulated 2 mm tip, designedand manufactured by Radionics Inc. (Burlington, MA).

For treatment of pain after brachial plexus avulsion, the electrode penetratesthe dorsolateral sulcus to a depth of 2 mm at an angle of 25–45° in the lateral–medial direction. A series of RF coagulations are made under a current of35–40 mA (not over 75°C) for 10–15 s. The RF lesions are spaced at 2–3 mmintervals along the longitudinal extent of the dorsolateral sulcus. The lesionobserved under magnification is seen as a circular whitened area that extends1–2 mm beyond the tip of the electrode.



In a recent publication, Nashold emphasizes the importance of obtainingimpedance measurements from tissue during surgery [53]. Before and aftereach lesion is made, the impedance has to be measured. It is usually lessthan 1200 Ω in a damaged spinal cord. The authors state that as the transi-tion from injured parenchyma into more normal tissue is made, impedancereadings should increase and eventually reach normal levels of 1500 Ω. Theauthors use these numbers as a guide to stop the lesion making at the desiredend.

3 DREZ PROCEDURES WITH THE LASER BEAM

Levy et al. in 1983 [37] and Powers et al. in 1984 [38] advocated CO2 andargon lasers, respectively, as lesion makers. According to Levy et al.’s descrip-tion, the pulse duration of the CO2 laser is 0.1 sec and the power is adjustedto about 20 W, so that one or two single pulses create a 2 mm depression ata 45° angle in the DREZ. The lesions are probed with a microinstrumentmarked at 1 mm increments to ensure that the depth of the lesions (1–2 mm)is adequate.

Intraoperative observations in humans and experimental studies comparingDREZ lesions performed with the RF thermocoagulation to those made withvarious laser beams [54] found that the laser lesions were generally more cir-cumscribed and less variable. Walker et al. [55], on the other hand, reportedon the danger of creating extensive damage and syrinx cavities with the laser(CO2). In a well-documented study evaluating the effects of DREZ lesions withRF or CO2 on the dog spinal cord, Young [56] found that the size and extentof the lesion related primarily to the magnitude of power used to make thelesion. They showed that by using any of the three techniques, the lesionscould be successfully localized to the DREZ (including the layers I–VI of thedorsal horn) and the dorsal column and the corticospinal tract spared. The maindifference was that with the laser, the lesion was shaped like the letter “V”, withthe maximum width at the surface, whereas with RF it tended to be more spher-ical. The same glial reactions were observed using both methods in chronicanimal models.

Young [57], in his series of patients, made a comparative analysis of RF andCO2-laser procedures. With RF, 39 of the 58 patients (67%) reported goodresults (pain regressed by 50% or more) and with the CO2 laser, 9 out of the 20patients (45%) reported good results. Postoperative complications with RFwere noted in 26%, and with CO2 laser in 15%.



4 ULTRASONIC DREZ PROCEDURE

This procedure was developed by Kandel and Dreval [39, 40] in Moscow. Ithas been mostly used for pain caused by brachial plexus avulsion. Accordingto the description given by Dreval, the technique consists of a continuous lon-gitudinal opening of the dorsolateral sulcus at the level of the avulsed rootsto the depth of the microcavities and the changed spongy cord tissue. At thesame time, ultrasonic destruction of the pathological tissues is done. Thelesion is strictly in the projection of the dorsolateral sulcus at an angle of 25°medially and ventrally. The depth of the microcavities is the main criterionof the depth of the lesioning. After ultrasonic DREZ sulcomyelotomy, thegrey color of the dorsal horn is well seen in the depth of the opened dorso-lateral sulcus. The vessels crossing the sulcus are kept intact. The ultrasoniclesions are produced at a working frequency of 44 kHz, and the amplitude ofultrasonic oscillation is 15–50 µm. The lesions are placed in a “chain” manneralong the sulcus.

5 INDICATIONS FOR DREZ

Because of our experience with 362 patients operated on since 1972 for severechronic pain [58] and in consideration of the literature data [59], we concludethat indications are as follows:

1. Cancer pain that is limited in extent (such as in Pancoast-Tobiassyndrome).

2. Persistent neurogenic pain that is due to: A) Brachial plexus injuries, especially those with avulsion.B) Spinal cord lesions, especially for pain corresponding to segmental

lesions. Pain below the lesion is not favorably influenced. Segmentalpain caused by lesions in the conus medullaris and the cauda equinais significantly relieved. Pain due to cauda equina lesions can alsobe indications.

C) Peripheral nerve injuries, amputation, and herpes zoster, when thepredominant component of pain is of the paroxysmal type and/orcorresponds to provoked allodynia hyperalgesia.

3. Disabling hyperspasticity with pain.

Surgery in the DREZ must be considered alongside other methods belong-ing to the armamentarium of pain surgery. Figure 5.8 summarizes our presentprocess of decision making for neuropathic pain [60].



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FIGURE 5.8 Decision making for neuropathic pain, originating from the following: upper left,peripheral nerves, plexus, roots distal to ganglion lesions; upper right, roots central to ganglionlesions; lower right, incomplete and complete spinal cord lesions; lower left, treatment for the seg-mental and the infralesional components of the pain are different.



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119Book TitleCopyright line

C H A P T E R 6

NeurophysiologicalMonitoring DuringEndovascular Procedureson the Spine and the Spinal CordFRANCESCO SALA

Section of Neurosurgery, Department of Neurological Sciences and Vision,Verona University, Verona, Italy

YASUNARI NIIMI

Center for Endovascular Surgery, Hyman-Newman Institute for Neurology and Neurosurgery, Beth Israel Medical Center, New York

1 Spinal Cord Vascularization and Ischemia1.1 Vascular Anatomy of the Human Spinal Cord1.2 Primers on the Pathophysiology of Spinal Cord

Ischemia Secondary to Spinal Cord Vascular Malformations

2 Neurophysiological Monitoring2.1 Evoked Potentials in Spinal Cord Ischemia:

Experimental and Clinical Studies2.2 Clinical Application of Neurophysiological

Monitoring for Endovascular Treatment of Spine and Spinal Cord Vascular Lesions

3 Endovascular Treatment of Vascular Malformations and Tumors of the Spine and the Spinal Cord3.1 Indications3.2 Angiographic Vascular Anatomy of the Spine

and Spinal Cord3.3 Spinal Angiography

Neurophysiology in Neurosurgery: A Modern Intraoperative ApproachCopyright 2002, Elsevier Science (USA). All rights of reproduction in any form reserved.


120 Francesco Sala and Yasunari Niimi

3.4 Angiographic Evaluation, Endovascular Treatment, and Clinical Aspect of Neurophysiological Monitoring

4 ConclusionsReferences

ABSTRACT

After reviewing the vascular anatomy of the spinal cord and the pathophysiology ofspinal cord ischemia, this chapter will discuss the role of neurophysiological monitor-ing in animal studies and during ischemic events in the human spinal cord. In orderto assess the feasibility and reliability of neurophysiological monitoring, we will pre-sent data from a series of 110 consecutive endovascular procedures performed undergeneral anesthesia with neurophysiological monitoring. The different but comple-mentary roles of MEP and SEP monitoring will be discussed together with the criticalimportance of provocative tests using Amytal and Xylocaine. Finally, primers on theangiographic vascular anatomy of the spine and spinal cord and on the endovascularprocedures aimed to treat these hypervascular lesions will be given. Examples of par-ticularly challenging procedures in spinal interventional neuroradiology, and the ben-efit of neurophysiological assistance during these procedures, are presented.

1 SPINAL CORD VASCULARIZATION AND ISCHEMIA

1.1 VASCULAR ANATOMY OF THE HUMAN

SPINAL CORD

Before describing the role of neurophysiological monitoring during endovas-cular procedures aimed to treat spinal hypervascular lesions, an overview onthe vascular anatomy of the normal spinal cord is mandatory. Although werefer the reader to classical textbooks and articles for a detailed analysis of thevascular anatomy and the wide range of variations, here we will conciselydescribe those aspects relevant to the discussion of intraoperative neurophys-iological techniques.

During early embryonal development, each somite receives one pair of so-called segmental arteries arising from the dorsal aorta. Blood supply to theneural crest is then provided by a dorsomedial division of the ipsilateral seg-mental artery, the dorsospinal artery. This vessel supplies the neural tube viapaired ventral longitudinal arteries. Dorsally oriented branches of these ventralarteries penetrate deeply into the ipsilateral half of the neural tube. A networkof capillaries around the neural tube then organizes into longitudinal arterialaxes. Between the sixth week and the fourth month of uterine life, the cranio-caudal formation of a more mature vascular pattern is characterized by the ven-tral migration and then fusion of the ventral longitudinal arterial axes to formthe anterior spinal axis. On the posterior aspect of the cord, the pial networkorganizes into paramedian dominant axes that will give rise to two posterolateral


Neurophysiological Monitoring During Endovascular Procedures 121

spinal axes. Like the embryonal circulation of other systems, a multistagerearrangement of the original radicular feeders to the ventral and posterior axesalso occurs. As a result of this process, no more than 4 to 8 anterior and 10 to20 posterior radicular arteries remain by the end of development.

In the adult, we observe three main longitudinal arterial systems. The anteriorspinal artery (ASA) extends almost uninterrupted from the medulla to the filumterminale. At the cervicomedullary junction it originates from the two vertebralarteries near the vertebrobasilar junction. Caudally, the major blood supplycomes from dorsal branches of intercostals and lumbar arteries. The major radicu-lomedullary arteries arise, at the level of the cervical enlargement, from vertebral,deep cervical, or ascending cervical arteries. The thoracolumbar territory is sup-plied mainly by the arteria radicularis anterior magna or “artery of Adamkiewicz.”This usually rises from the ninth to the twelfth intercostal artery, on the left sidein approximately 80% of the cases. It gives off a small ascending branch and alarge descending branch that anastomoses with the posterior spinal arteries toconfigurate the anastomotic basket surrounding the conus medullaris [1–3].

Because of its segmental vascularization, each major arterial group (cervical,upper thoracic, and Adamkiewicz) irrigates its own portion of the cord with-out significant anastomoses with other groups. Consequently, the spinal cordis typically vulnerable to hypoperfusion at the middle thoracic level.

The paired posterior spinal arteries arise, at the cervical level, either from thevertebral arteries or, less frequently, from the posteroinferior cerebellar arteries.Caudally, these paired posterior spinal axes receive radiculopial feeders alsofrom the vertebral, intercostal, and lumbar arteries, and they are located on theposterolateral surface of the cord adjacent to the dorsal root entry zone. Thenumerous anastomoses in this posterior system decrease the risk of ischemia forthe posterior spinal cord.

From a neurophysiological perspective, it is important to bear in mind thatthe direction of spinal cord blood flow (SCBF) at any level in the cord cannotbe easily predicted because it depends on the location of the dominant anterioror posterior spinal artery for that segment of the cord [4]. Nevertheless, as sum-marized in Fig. 6.1 (see also color plate), the ASA, through perforating sulco-commissural arteries, is assumed to supply the anterior two thirds to four fifthsof the cord, including the anterior column of the central grey matter, the ante-rior and lateral corticospinal tracts, and the anterior and lateral spinothalamictracts. The ASA therefore accounts for vascularization of those structuresinvolved in the propagation of motor evoked potentials (MEPs) from their cor-tical generators to the α-motoneurons: the anterior and lateral corticospinaltracts (CSTs) and, to a lesser extent, the propriospinal system. Conversely, theposterior spinal arteries (PSAs) supply the posterior horns of the central greymatter and the dorsal columns; although the debate is still open, these posteriorcolumns are usually considered the main tracts for central propagation ofsomatosensory evoked potentials (SEPs) after peripheral stimulation [5].



Circumferential vessels from the ASA anastomose with the PSAs through acomplex pial network, the so-called vasa corona [6], which supplies the periph-eral rim of the white matter and represents a functionally relevant dorsoventralconnection. Therefore, in the axial plane, the watershed zone of the cord islocated in the anterior two thirds of the cord in the white matter adjacent to theanterior horn cells, where penetrating branches from the ASA and PSA meet atthe circumferential pial network [7].

The complexity of both longitudinal and axial angioarchitecture of the vascu-lar supply to the spinal cord accounts for the unpredictability of hemodynamic

FIGURE 6.1 Schematic representation of spinal vascular anatomy and its relationship with longtracts involved in the generation of somatosensory and motor evoked potentials. 1. Posterior spinalarteries. 2. Posterior spinal vein. 3. Anterior spinal artery. 4. Anterior spinal vein. 5. Spinal ventralroots. 6. Anterior corticospinal tracts. 7. Lateral corticospinal tracts. 8. Dorsal columns. (Modifiedfrom Nieuwenhuys, R., Voogd, J., and van Huijzen, C. (1988). The human central nervous system:A synopsis and atlas, rev. ed. 3. Springer Verlag, Berlin) (see also color plate).



patterns in the spinal cord; the direction of SCBF becomes even more bizarre inthe presence of a vascular malformation that interferes with normal patterns.

Although studies on spinal cord vascular anatomy have mainly focused onthe arterial circulation, it has to be emphasized that venous anatomy is equallyessential, since it is dramatically involved in the pathophysiology of most vas-cular malformations. Although venous anatomy is even more unpredictablethan its arterial counterpart, two drainage pathways are usually considered.

Sulcal veins drain blood from the central portion of the cord through theanterior median fissure into the anterior median spinal vein; this receives bloodfrom tributaries of central veins that drain the central grey matter, including theanterior horns. A dorsal spinal vein, often larger than the anterior one, drains

FIGURE 6.2 Left, schematic illustration of the anatomic relationship between the aorta (AO), theintercostal artery (ICA), and the radiculomedullary artery (RMA) contributing to the anterior spinalartery axis (ASA). A spinal cord (SC) arteriovenous malformation (AVM) is represented. Xylocaineinjected during a provocative test is schematically represented by open circles (modified from [58]with permission from Elsevier). Right, typical example of mMEP behavior after provocative testwith Xylocaine injection at different catheter positions within the ASA. Top, muscle motor evokedpotentials (mMEPs) are elicited through transcranial electrical stimulation and recorded fromneedle electrodes inserted in the tibialis anterior muscle. Middle, when the tip of the catheter isin position 1, the injected Xylocaine will flow through vessels feeding the normal spinal cord(a). Provocative test will be positive: absence of the mMEP from the tibialis anterior muscle (TA).Bottom, when the tip of the catheter is more selectively advanced to position 2 or 3, Xylocaine willbe injected only in vessels feeding the AVM (b and c) and, accordingly, the provocative test will benegative: persistence of mMEP from the TA. Reprinted from [57].



the posterocentral portion of the cord. The radial or coronal veins originatefrom capillaries at the gray–white junction, coursing centrifugally and drainingthe anterolateral and dorsal regions of the spinal cord.

The final common pathway of spinal cord venous drainage is through the radic-ular veins that pierce the dura to drain into the epidural veins; these radicularveins lack valves but typically narrow at the dural penetration to prevent ret-rograde venous flow [8].

1.2 PRIMERS ON THE PATHOPHYSIOLOGY OF SPINAL

CORD ISCHEMIA SECONDARY TO SPINAL CORD

VASCULAR MALFORMATIONS

More recent classifications of spinal cord vascular malformations include a numberof lesions whose characteristics will be described later in this chapter. However,regardless of their specific hemodynamics, the final common pathway in thepathophysiology of these lesions is spinal cord ischemia or hemorrhage. Basically,in both the arteriovenous malformations and in the fistulas, the main mechanismis the lack of a capillary bed and a direct shunt of the arterial blood into the venouscompartment. This arteriovenous shunt leads to vascular steal phenomena fromthe adjacent normal vasculature; the more the malformation shares its arterialsupply with the normal spinal cord, the more the cord will be exposed to a vascu-lar steal, and therefore to an ischemic injury. On the venous side, a multifactorialphenomenon leads to venous hypertension and thrombosis. Venous inflow isincreased because of direct arterial feeders; venous outflow is sometimes compro-mised by a malfunctioning of the valve system of radicular veins when these piercethe dura (which contributes to venous engorgement). A subacute necrotizingmyelopathy resulting from thrombosis of a spinal arteriovenous malformation(AVM) has been described as the Foix-Alajounine syndrome [9]. The coexistenceof venous or arterial aneurysms increases the risk for subarachnoidal and parenchy-mal hemorrhages, which account for the acute onset of symptoms in intraduralAVMs. Arachnoiditis may evolve from repeated hemorrhages.

2 NEUROPHYSIOLOGICAL MONITORING

2.1 EVOKED POTENTIALS IN SPINAL CORD

ISCHEMIA: EXPERIMENTAL AND CLINICAL STUDIES

Most data on the role of neurophysiological techniques in decreasing the inci-dence of spinal cord ischemia come from thoracoabdominal aneurysm surgery.The role of SEPs and MEPs in detecting cord ischemia and preventing irre-versible neurological deficits has been investigated both in experimental animalmodels and in clinical studies.



Konrad et al. tested the sensitivity of MEPs recorded epidurally from thespinal cord as well as from the peripheral nerve after direct cortical stimulationof the motor cortex in dogs. The peripheral nerve response appeared to be verysensitive to cord ischemia after cardiac arrest when compared to the late disap-pearance of the spinal cord response [10].

Similarly, Kai and coworkers concluded that peripheral neurogenic MEPsprovide a better warning system for spinal cord ischemia than spinal MEPs andSEPs recorded from peripheral nerves after stimulation of the spinal cord;unfortunately, the spine-to-spine response is not specific, since it activatesneural pathways both orthodromically and antidromically [11].

Laschinger et al. investigated spinal cord ischemia after thoracic aortic cross-clamping in dogs. He documented a time- and level-dependent deteriorationand loss of the spinal cord response recorded from subcutaneously insertedspinal electrodes after spinal cord stimulation at T3–T4. This suggests thatischemia begins in the most distal cord, progresses upwardly, and can be pre-vented by maintaining an adequate distal aortic perfusion [12].

Similar results on the higher vulnerability of the lower spinal cord werereported by Reuter and coworkers, who correlated MEPs to ischemic spinaldamage after aortic occlusion in dogs; the greater portion of cord damage wasconfined to the grey matter of the caudal segments of the cord [13]. This mightbe related to a discontinuous ASA; if the lumbar cord relies only on theAdamkievicz artery for its blood supply, occlusion of this artery would not becorrected by collateral feeders and perfusion would be inadequate. Theseauthors also confirmed the early disappearance of the peripheral nerve MEP,which was considered even too sensitive as an indicator of spinal cord damage.Conversely, they found a clear correlation between spinal MEPs after brainstimulation, spinal cord perfusion, and histopathologic findings. In the samestudy, SEPs appeared to be more sensitive than spinal MEPs to ischemia [13].

Concerning the different role of spinal MEPs as compared to peripheralnerve MEPs, it is noteworthy that Reuter et al. observed the presence of spinalMEPs but the absence of peripheral nerve MEPs 24 hr after cord ischemia, whenanimals were paraplegic. This was explained on the basis of histological find-ings, since the damage was primarily confined to the gray matter but did not sig-nificantly affect the white matter, where propagation of the descending volleyswas preserved [13]. To elicit peripheral nerve MEPs after brain stimulation,conversely, requires the functional integrity of the anterior horns.

A similar comparison of the sensitivity between spinal and muscle MEPs(mMEPs) after transcranial electrical stimulation in the detection of spinal cordischemia was performed by de Haan et al. [14]. They concluded that mMEPs dis-appear earlier and are therefore more sensitive than epidural MEPs, suggestingtheir clinical use to assess spinal cord perfusion during surgery at risk for ischemia.Early disappearance of mMEPs is secondary to the polysynaptic transmission ofthis potential, so that a reduction in SCBF that affects the functional integrity of



the anterior horns will switch off neural transmission at that level. Epidurallyrecorded MEPs, conversely, are more robust, since no synapses are involved andwhite matter is more resistant to ischemia than grey matter [10, 13, 15, 16].

In the past few years, along with experimental work, there has been increas-ing clinical evidence of the usefulness of neurophysiological monitoring duringthoracic aorta surgery. For a long time, SEPs have been used to assess the func-tional integrity of the spinal cord [5, 17, 18]. Unfortunately, SEPs are aimed atmonitoring the dorsal column and the posterior spinal cord, but they do notreflect the functional integrity of motor pathways. Dorsal column response toischemia, moreover, is relatively slow [18], and SEP monitoring cannot detectischemia in time to revert the injury before irreversible neuronal damage occurs.

Machida et al. [19] described a dissociation of mMEPs (after spinal cord stim-ulation) and SEPs (also following spinal cord stimulation) resulting from ischemicdamage to the spinal cord in both an experimental setting as well as during spinalfusion with Cotrel-Dubousset instrumentation; because of the greater vulnerabil-ity of mMEPs to ischemia when elicited by this method, they suggested the use ofmMEPs as a sensitive measure of anterior cord function. Similarly, de Haan et al.proposed mMEPs after transcranial stimulation as optimal tools for assessing thestatus of motor pathways from the cortex to the muscle [20, 21]. In their experi-ence, mMEPs turned out to be sensitive and specific, since they correctly pre-dicted motor outcome in all patients with no false-negative (postoperative motordeficits despite unchanged motor evoked response) or false-positive results (sig-nificant changes in intraoperative MEPs despite unchanged motor outcome).

It is less likely that spinal cord surgery could damage the anterior horn greymatter while leaving the white matter intact. The opposite is true during spinalcord embolization because of the selectivity of spinal cord vascularization. Forgeneration of epidural MEPs after transcranial electrical stimulation, only intactlong motor tracts are necessary. The generation of mMEPs after transcranialelectrical stimulation, however, depends on long motor tracts and the segmen-tal level anterior horn grey matter. Therefore, mMEPs should be a better mon-itoring tool for endovascular embolization of the spinal cord vessels.

2.2 CLINICAL APPLICATION

OF NEUROPHYSIOLOGICAL MONITORING

FOR ENDOVASCULAR TREATMENT OF SPINE

AND SPINAL CORD VASCULAR LESIONS

Endovascular techniques are increasingly used in the treatment of hypervascularlesions in the spinal cord and surrounding structures. The injection of embo-lizing materials has proven useful in the devascularization of spinal cord tumorsand the occlusion of intramedullary, dural, or spinal arteriovenous malformations



or fistulas [22–29]. The occurrence of vasospasm or the unrecognized obliterationof vessels feeding the normal spinal cord, however, put the spinal cord at riskfor ischemia. If ischemia is not detected in time before irreversible damage hasoccurred, patients can suffer from permanent neurological deficits [30–33].

Since a detailed angiographic study and the following embolization can lastfor several hours, these procedures are often performed under general anesthe-sia, which also allows for an optimal angiographic study, as discussed later. Inthe past, a so-called wake-up test was performed to assess the neurologicalstatus of the patient immediately after any critical maneuver. These tests, how-ever, prolong the procedure, carry discomfort to the patient, and might take toomuch time before protective measures are readily available. The greater relia-bility of neurophysiological monitoring in detecting spinal cord ischemia, whencompared to the wake-up test, has been established for spine surgery [34, 35].

Through the years, intraoperative neurophysiological monitoring has beenproposed as a valid alternative to the wake-up test to assess the functionalintegrity of neural pathways during endovascular procedures. Somatosensoryevoked potentials have been used since the mid-1980s [36–38] based on theclinical evidence that SEPs were sensitive to compromises in anterior spinalartery circulation [36]. Concerns about the reliability of SEPs in evaluating theintegrity of descending motor tracts during spine and spinal cord surgery[39, 40], as well as during aortic surgery [41, 42], have then appeared in theliterature. As previously discussed in this chapter, the occurrence of a motordeficit despite intraoperatively unchanged SEPs is explained by the limited abil-ity of SEPs to assess the functional integrity of corticospinal tracts. Neverthe-less, despite the advent of reliable techniques to elicit MEPs under generalanesthesia [43, 44], reports on the use of MEPs during endovascular proceduresin the spinal cord remain anecdotal [45–48].

In the following sections we describe the protocol we currently use at theInstitute for Neurology and Neurosurgery to perform multimodal neurophysi-ological monitoring during endovascular treatments.

2.2.1 Patient Setup and Anesthesiological Management

In order not to delay the beginning of the endovascular procedure, it is desir-able to have the anesthesiologist and the neurophysiologist working together inpreparing the patient. As for any intraoperative neurophysiological monitoringprocedure, the greater the collaboration between these two teams, the moreeffective will be both the anesthesiological and neurophysiological managementof the patient. Although the basic setup of the patient does not differ from thatoccurring during any other neurosurgical procedures, it is important to bearin mind that in the angiography suite the patient can be moved upward anddownward along the operating bed and that the angiographic machine may be



rotated around the main axis for angiographic purposes. This implies carefulplacement of cables for evoked potentials stimulation and recording in order toavoid stretching of the wires or interference with the angiographic steps.

Electrodes for intraoperative neurophysiological monitoring (IOM) arehooked up as for any other surgical procedure where IOM is used. The standardneurophysiological monitoring consists of SEPs and mMEPs. We use the AxonSentinel-4 evoked potential system with modified software (AXON Systems,Inc., Hauppage, NY) for both stimulation and recording. SEPs are elicited bystimulation of the median nerve at the wrist (intensity up to 40 mA, duration0.2 ms, repetition rate of 4.3 Hz) and the posterior tibial nerve at the ankle(intensity up to 40 mA, duration 0.2 ms, repetition rate of 4.3 Hz). Recordingsare performed via corkscrew-like electrodes inserted subcutaneously in the scalp(CS electrode, Neuromedical Inc., Herndon, VA) at C3′/C4′–CZ′ (median nerve)and at CZ′–FZ (tibial nerve) according to the 10–20 International EEG System.

The mMEPs are elicited with transcranial electrical stimulation of the motorcortex using CS electrodes. Short trains of up to seven square-wave stimuli of500 µs duration each and interstimulus intervals of 4 ms are applied at a repe-tition rate of 2 Hz and intensity up to 200 mA, through electrodes placed at C1and C2 scalp sites, according to the International 10–20 EEG System. Muscleresponses are then recorded via needle electrodes inserted into the abductor pol-licis brevis (APB) and hypothenar muscle for the upper extremities and into thetibialis anterior (TA) and abductor hallucis brevis (AHB) muscles for the lowerextremities, bilaterally. This technique has been used at our institution to moni-tor over 100 spinal cord tumor cases and is described in detail elsewhere [49, 50].

A more invasive technique for monitoring MEPs was described in 1991 byKatayama et al. [46]. This author elicited MEPs through a burr hole with corti-cal epidural stimulation and spinal epidural recording, proposing this method asan optimal and specific tool to assess the functional integrity of the CST. At thepresent time there is no need for such an invasive monitoring procedure sincemMEPs are easily elicitable using multipulse transcranial stimulation. We usu-ally do not monitor spinal epidural MEPs during these procedures since thesepatients may receive a considerable amount of heparine by the end of the proce-dure and trancutaneous placement of an epidural catheter for spinal recordingwould therefore be hazardous. Furthermore, as previously mentioned, data fromexperimental studies suggest that monitoring only epidural MEPs (D waves) willnot cover the functional integrity of α-motoneurons, and, because of the higherresistance of white matter to ischemia, warning signs from this monitoringmodality could be too delayed to allow prompt restoration of spinal cord perfu-sion. According to our experience with IOM during spinal cord tumor surgery[49, 50], both muscle and epidural MEPs are required for optimal IOM to pre-dict outcome. For endovascular procedures, however, mMEPs are sufficient.

Whenever the lesion involves the lumbosacral segments of the spinal cord,we add the monitoring of the bulbocavernosus reflex (BCR) to the battery of



neurophysiological tests [51]. This oligosynaptic reflex allows us to assess thefunctional integrity of both the afferent and efferent fibers of the pudendalnerves together with the reflex center located in the gray matter at S2–S4 spinalsegments. For stimulation of the dorsal penile nerve (pudendal afferents), twosilver/silver chloride disc electrodes are placed on the dorsal aspect of thepenis with the cathode proximal. In female patients, the cathode is placedover the clitoris and the anode over the labia majora. Rectangular pulses of 0.2to 0.5 ms duration are applied as a train of five stimuli (interstimulus intervalsof 4 ms) at a repetition rate of 2.3 Hz. Stimulus intensities do not exceed 40 mA.Recordings are made from the external anal sphincter muscle using two pairsof intramuscular Teflon-coated hooked wire electrodes inserted into the analhemisphincters.

The optimal neuroanesthesiological management compatible with intraop-erative neurophysiological monitoring is discussed in Chapter 17 of this book.For interventional procedures, we use a continuous infusion of propofol (100–150 µg/kg/min) and fentanyl (1 µg/kg/h), avoiding boluses. No halogenatedagents or muscle relaxants are given after intubation. These parameters, whileallowing an easier management of the interventional procedure and optimiza-tion of the angiographic results, warrant an anesthesia slightly lighter than thatused for major surgical procedures so that patients can be quickly and easilyawakened at the end of the procedure.

Baseline traces of evoked potentials are taken at the beginning of the proce-dure. Because of the possibility of vasospasm secondary to a vessel catheteriza-tion, it is important to obtain baselines after anesthesia induction but before anyangiographic maneuver occurs. If not recognized, this event could lead toischemic derangements of the cord (see Fig. 6.6C, right). Since MEPs couldinduce muscle twitches that interfere with the imaging, it is preferable not torun mMEPs while the radiologist is performing the angiography. Muscle MEPs,however, do not need averaging and can be quickly assessed immediately afterany relevant angiographic step. Conversely, neither the BCR nor the SEPs inducetwitches and therefore can be continuously monitored.

With regard to the feasibility of evoked potentials during endovascular pro-cedures, results from our series demonstrate that these potentials are easily elic-itable in the majority of the patients, unless severe neurological deficits havealready compromised the functional integrity of neural pathways. In over 110endovascular procedures in 87 patients who were treated for spine and/or spinalcord vascular lesions between 1996 and 1999, monitorability of evoked potentialswas 80% for SEPs, 85% for the BCR, and 92% for mMEPs. Monitorability isdefined as the presence of a reliable response after the induction of anesthesiabut before any interventional procedures. There were no significant differencesin monitorability between males and females for MEPs and SEPs, while the BCRseemed more difficult to elicit in females, most likely because of technical dif-ficulties in placing stimulating electrodes.



2.2.2 Endovascular Procedure and Provocative Tests

Figure 6.3 summarizes the protocol for spinal endovascular embolization usedat our institution. The first step of the procedure consists of a detailed and care-ful investigation of the vascular anatomy. This is necessary for successful treat-ment, independent of any additional neurophysiological support. More detailson the angiographic protocols used for each disease category have been pro-vided later in this chapter (see Section 3). Regardless of the pathology to betreated, a critical step of IOM during endovascular procedures is the so-calledprovocative test. Provocative tests are aimed at assessing the safety of a plannedembolization, since they pharmacologically mimic the effects of the embolizationitself. Because of the intimate relationship of the malformations with the spinalcord vascularization, the embolization of an intradural AVM is the most riskyprocedure and one that we will refer to in discussing the role of provocativetests. To access an intradural spinal AVM, the catheter is introduced in the pedi-cle artery and then superselectively advanced into the spinal cord artery (ASA orPSA) feeding the AVM. Once the catheter has reached the embolizing position,but before any embolizing material is injected, provocative tests are performed.

This sort of “Wada test” [52] for the spinal cord consists of the intra-arterialinjection of the short-acting barbiturates amobarbital (Amytal) and lidocaine(Xylocaine) through a microcatheter. Amytal blocks neuronal activity, and Xylo-caine blocks axonal conduction [53, 54]. Therefore, a positive Amytal or Xylo-caine test (i.e., more than 50% decrease in SEP amplitude and/or mMEP dis-appearance) indicates that the vessel distal to the tip of the microcatheter suppliesthe functional grey or white matter of the spinal cord, respectively (see Fig. 6.2).

FIGURE 6.3 Protocol for spinal endovascular procedures using provocative tests (see text fordetails).

Identification of the ASA and PSAs supplying normalspinal cord below and above the AVM

Identification of the angioarchitecture of the AVM

Selective catheterization of the pedicle artery

Superselective catheterization of the ASA or PSA feeding the AVM

Provocative tests+

+

—

—

+

No embolization from that specific catheter position

More selective catheterization or attemptsto embolize through other feeding vessels

Embolization

Provocative tests

Abandoned embolization

Embolization



If a provocative test is positive, liquid embolization from that catheter posi-tion should not be performed. Instead, a superselective angiogram from themicrocatheter should be carefully reviewed to assess the following possibilities:(1) to further advance the microcatheter distally to bypass the vessel supplyingthe normal spinal cord; (2) to protect the normal spinal cord supply before theliquid embolization, as shown in Fig. 6.7; or (3) to use particulate embolicagents. If none of these is feasible, embolization should be attempted from otherfeeders or completely aborted [48] (Fig. 6.7).

In rare circumstances provocative tests may overestimate the effects ofendovascular obliteration [55] because of local hemodynamic or nonselectivecatheterization of the AVM feeder. This is the case when the sizes of theembolizing material, such as particles or coils, are bigger than the diameter ofthe small arteries feeding the normal spinal cord. In this case Xylocaine, whichis liquid, could easily diffuse through the vascular tree into those vessels feed-ing the AVM as much as in those feeding the normal spinal cord, and provoca-tive tests will be positive. However, relying on the different diameter betweenthe enlarged vessels of the AVM and the small feeders to the normal cord, inselected cases it is still possible to safely proceed with the embolization. A non-selective catheterization of the vessels feeding the malformation could alsoinduce a spreading of the provocative drug to the normal spinal cord and there-fore give a positive test result. Overall, however, these tests have proven to bevery useful in enhancing the safety of endovascular procedures for spine andspinal cord vascular lesions [48, 56–58].

We have performed more than 30 provocative tests with Amytal and Xylocaineduring endovascular procedures in the spinal cord. In our experience, Xylocainetests are more often positive than are Amytal tests. This is most likely due tothe different site of action of the two drugs. Xylocaine acts mainly on axonalconduction, whereas Amytal switches off neuronal activities without suppress-ing axonal conduction [53, 54]. Nevertheless, since these drugs test differentpathways of the spinal cord, both should be used in every patient undergoinga spinal embolization.

It is also noteworthy that we had no cases in which both SEPs and mMEPswere affected simultaneously after either Amytal or Xylocaine injection(Table 6.1). This suggests that to monitor only SEPs or only mMEPs wouldexpose the patient to the risk of neurological deficits [57]. Although, in ourseries, provocative tests affected mMEPs more than SEPs, mMEPs should beused as a complement rather than as an alternative to SEP monitoring. In fact,the possibility of selective sensory deficits with preserved motor functionduring removal of a spinal AVM and its correlation with neurophysiologicaltests has been described [59].

The need for multimodal (mMEPs and SEPs) neurophysiological monitor-ing comes also from the observation that there is no correlation between the



vascular compartment where the provocative test is performed (ASA or PSA) andthe neurophysiological modality that is affected (SEPs or mMEPs) (Table 6.2).The unpredictability of provocative tests when Amytal or Xylocaine is injectedin the ASA and/or PSA supports the existence of vascular anastomoses and thevariability of the spinal cord flow dynamic, the latter being even more complexin the presence of an AVM. Touho et al. described motor, but not sensory,deficits as a result of Xylocaine injection in the ASA [58]. Vice-versa, we haveexperienced one case where injection of Amytal or Xylocaine in the ASAcaused loss of SEPs while mMEPs remained unchanged. Therefore, we routinelymonitor SEPs as well as mMEPs even if the endovascular procedure is limitedto the ASA territory. Because any interventional procedure may acutely modifythe local hemodynamic, it is also critical to repeat provocative tests for bothSEPs and MEPs before each embolization procedure.

We performed neurophysiological monitoring during 110 endovascular pro-cedures in 87 patients who were treated for spine and/or spinal cord lesionsbetween 1996 and 1999. In terms of neurological outcome, two patients woke upwith a paraparesis, one moderate and one severe, that was not present before theprocedure. Paradoxically, both of them belong to a group of 59 patients who wereconsidered at low risk because they harbored extramedullary vascular lesions that

TABLE 6.1 Results of Provocative Tests

mMEPsmMEPs SEPs drop disappearance &

N° of tests Positive tests disappearance >50% SEPs drop >50%

Amytal 31 1 (3%) 1 0 0Xylocaine 33 9 (27%) 7 2 0

TABLE 6.2 Correlation between Positive Provocative Tests and Evoked Potentials

IntraoperativelyPositive tests Vessel changed EP

Amytal 1 (3%) PSA mMEPsXylocaine 9 (27%) PSA mMEPs

PSA mMEPsPSA SEPsASA mMEPsASA mMEPsASA mMEPsASA mMEPsASA SEPsPICA mMEPs

Legend: EP = evoked potentials; PSA = posterior spinal artery; ASA = anterior spinal artery.



were not in close vascular relationship with the spinal cord. In both these patients,however, provocative tests were not done, and neurophysiological monitoringcould only document the disappearance of mMEPs from the lower extremitiesand anticipate the neurological motor deficit. Conversely, whenever provocativetests were performed, either in the low-risk patients or in those harboringintramedullary AVMs or fistulas, neurological morbidity was never documented.

On the basis of our experience, we believe that our provocative test protocolhelps decrease the risk of spinal cord ischemia during endovascular procedures.Since it is unsafe and unethical to expose patients to the risk of embolizationafter a positive test (with the few exceptions already mentioned), controlledtrials are unlikely to occur. Accordingly, the ability to superselectively catheter-ize vessels feeding the vascular malformation is of paramount importance.

In the last sections of this chapter we will focus on the classification of spinalvascular lesions, their angiographic features, and principles of endovasculartreatment. Those aspects relevant to neurophysiological monitoring will beemphasized.

3 ENDOVASCULAR TREATMENT OF VASCULAR MALFORMATIONS AND TUMORSOF THE SPINE AND THE SPINAL CORD

3.1 INDICATIONS

All vascular lesions of the spine, spinal cord, and surrounding tissues may becandidates for endovascular embolization. The indications include preoperativetreatment to decrease vascularity (and therefore intraoperative blood loss), pal-liation for incurable diseases, and curative therapy when embolization alone iscurative. Various embolic agents are used, depending on the purpose of thetreatment and the nature of the disease. We will discuss endovascular emboliza-tion of these lesions and the implication of neurophysiological monitoring.

3.2 ANGIOGRAPHIC VASCULAR ANATOMY

OF THE SPINE AND SPINAL CORD

The vascular supply to the spine and paraspinal musculature arises from themain trunk of the intercostal or lumbar artery as well as the dorsospinal artery[60]. Vascular supply to the spinal dura and spinal cord is derived from the ven-tral division of the dorsospinal artery. There are rich longitudinal and transverseanastomoses between the adjacent segmental arteries. Longitudinal anastomotic



vessels connect branches of the segmental arteries to adjacent branches aboveand below. Transverse anastomotic vessels connect right and left segmentalarteries across the midline. Both longitudinal and transverse anastomotic ves-sels can be outside or inside the spinal canal. Nerve roots and the spinal duraare supplied by the radicular artery arising from each segmental artery. Pro-gressing caudally from the intercostal to the lumbar levels, there is increasingobliquity of both the nerve roots and the radicular arteries because of differ-ences in the growth rate between the spine and spinal cord. If a radicular arterysupplies the ASA, it is called a radiculomedullary artery, and if it supplies thePSA, it is called a radiculopial artery. A radiculomedullary artery and a radicu-lopial artery may have a common trunk.

Because the segmental arrangement during embryonic development, partic-ularly in the cervical region, several vessels must be angiographically evaluatedto delineate the vascular supply of the spine and spinal cord. At the cervicallevel, the ascending cervical artery, the vertebral artery, and the deep cervicalartery on both sides must be evaluated. Additionally, at the C1–C2 levels, theascending pharyngeal and occipital arteries should also be studied. For the tho-racolumbar levels, angiographic evaluation of the bilateral supreme intercostal,intercostal, and lumbar arteries is indicated. At the sacral level, bilateral lateralsacral and iliolumbar arteries arising from the internal iliac artery as well asmedian sacral artery may supply the sacral nerve roots, spinal cord, vertebrae,and parasacral musculature.

As previously mentioned, the spinal cord derives its vascular supply fromone anterior midline ASA and two posterolateral paramedian PSAs [61].Angiographically, the radiculomedullary artery has a characteristic hairpinconfiguration that continues to the ASA, which appears as a midline continu-ous longitudinal straight vessel. The ascending limb of the ASA may be opaci-fied from a large radiculomedullary artery. The ASA continues caudally to thefilum terminale and forms anastomoses with bilateral PSAs at the level of theconus [1]. The PSA appears as a relatively small paramedian longitudinalstraight vessel. The PSA axis is smaller and discontinuous compared to theASA axis. The radiculopial artery also forms a hairpin configuration that has amore acute angle than the radiculomedullary artery because of its paramedianlocation.

The venous drainage of the spinal cord is characterized by rich intra- andperimedullary anastomoses. The perimedullary veins form a rich venous plexusas well as two longitudinal collector veins in the midline on the anterior andposterior surfaces of the spinal cord (the anterior and posterior median spinalveins). These perimedullary veins can be angiographically opacified by injec-tion of a large radiculomedullary artery. They drain to the extradural internalvertebral plexus via the radicular veins and then to the paravertebral veins[62–64].



3.3 SPINAL ANGIOGRAPHY

Spinal angiography and subsequent endovascular treatment are best performedunder general anesthesia. This not only provides the patients with comfort, butalso allows for extended periods of apnea (up to 40 s) and thus provides theopportunity to obtain high-resolution images necessary to identify small spinalcord arteries and to evaluate slow flow lesions. For lower thoracic and lumbarlesions, glucagon may also be administered to limit bowel motion which degradesthe image quality.

It is important to identify spinal cord arteries and differentiate them from sur-rounding extradural vessels supplying osteomuscular structures. In order to iden-tify the midline ASA and paramedian PSAs, it is mandatory to perform spinalangiography in the exact posterior–anterior projection. This is sometimes impossi-ble because of distortion of the spinal column and cord from previous treatmentor a pathology, either associated with or unrelated to the target lesion. In such acase, oblique and lateral views may be necessary to identify the spinal cord vessels.

Pretherapeutic spinal angiography should evaluate the vascular anatomy ofboth the pathology and normal surrounding spinal cord. More details of ourangiographic protocol will be discussed under each disease category.

3.4 ANGIOGRAPHIC EVALUATION, ENDOVASCULAR

TREATMENT, AND CLINICAL ASPECT

OF NEUROPHYSIOLOGICAL MONITORING

3.4.1 Tumors

Vascular tumors are classified as benign or malignant. Malignant tumors can befurther classified as primary or metastatic. For the purpose of endovascularembolization, it is also useful to classify tumors as extramedullary or intra-medullary. Intramedullary tumors are supplied by the spinal cord arteries, andtheir embolization carries higher risk than extramedullary tumors which arenot supplied by the spinal cord arteries. Hemangioblastomas are the onlyintramedullary tumors that are candidates for embolization. These tumors arebenign but usually hypervascular and are embolized primarily as a preoperativeprocedure depending on the vascularity, location, and size of the feeding ves-sels of the tumor. Angiographic assessment and endovascular treatment areperformed in a manner similar to that used for intradural spinal cord vascularmalformations.

Intradural extramedullary tumors such as meningiomas and neurinomasare not usually very vascular and embolization is typically not indicated. Incontrast, vascular tumors located in the extradural or paraspinal compartments



are frequently amenable to embolization as a preoperative or palliative measure.These tumors include benign lesions such as hemangiomas, giant-cell tumors,and aneurysmal bone cysts. Embolization may also be performed for vascularextradural malignancies such as primary sarcomas, plasmacytomas, heman-giopericytomas, and metastatic carcinomas such as those from the breast, thyroid,kidney, and stomach.

We usually use particles such as polyvinyl alcohol (PVA) particles as theprimary embolic agent. Coils are used to protect normal territory from inad-vertent embolization. Liquid adhesive, such as n-butyl cyanoacrylate (NBCA),is not routinely used for tumors because of its higher potential risk of penetra-tion into the spinal cord artery. It may, however, be used in highly vasculartumors to obtain a better occlusive effect. For palliative embolization of malig-nant tumors, ethanol may also be used as an embolic agent and results in a long-lasting effect because of its cytotoxicity.

Pretherapeutic angiographic assessment should address the exact location,size, and configuration of the lesion. The feeding arteries and draining veins ofthe lesion as well as the associated vascular dynamics (i.e., presence of arterio-venous shunting) should be assessed. It is also important to determine if thereis ASA or PSA contribution at or near the level of the lesion. For this purpose,angiographic evaluation should include not only the assessment of bilateralsegmental arteries at the level of the lesion, but also at least two levels above andbelow the lesion. As previously discussed, in the case of distortion of the spineor spinal cord from the previous treatment, the disease itself, or the existenceof overlapping metallic stabilization instruments, oblique and lateral views maybe helpful to identify spinal cord arteries [65, 66].

The main purpose of neurophysiological monitoring for spinal or paraspinaltumor embolization is to detect masked and unrecognized spinal cord arteries.If the existence of a spinal cord artery is suspected but uncertain, provocativetesting may be performed by observing changes in SEPs or MEPs after injectionof sodium Amytal and Xylocaine from a microcatheter placed within the feedingvessel of the tumor. If any changes are noted in either SEPs or MEPs, aggressiveembolization from that catheter position should be avoided. Also, if a signifi-cant change in SEPs or MEPs occurs during an embolization procedure, spinalcord ischemia should be suspected and the procedure should be terminated tominimize the risk of permanent damage and maximize the possibility of recoveryof the spinal cord. Improvement of SEPs or MEPs after tumor embolization issometimes observed in association with clinical improvement. This phenomenonmost often occurs in a tumor with epidural extension and spinal cord com-pression and is probably due to decreased mass effect secondary to tumordevascularization. This improvement is an indicator of effective embolizationeither as a preoperative or a palliative treatment. An example of preoperativeembolization for a cervical spine tumor is presented in Fig. 6.4.



3.4.2 Vascular Malformations

Vascular malformations can be simply classified into dural/extradural orintradural lesions. This distinction is important because the risk of embolizationand the role of neurophysiological monitoring are significantly different forthese two categories.

3.4.2.1 Dural/Extradural Lesions

Dural/extradural lesions include spinal dural arteriovenous fistulas (SDAVFs),epidural or paraspinal arteriovenous malformations (AVMs) or fistulas (AVFs),and spine AVMs or AVFs. Endovascular embolization is indicated in all of theselesions, usually as a curative treatment but also sometimes for palliative or pre-operative therapy. We prefer to use a liquid adhesive, such as NBCA, as anembolic agent because of its ability to penetrate into small vessels and its perma-nent occlusive effect. For the permanent cure of an AVF, the liquid embolic mate-rial should penetrate into the proximal portion of the draining vein through thefistula site [67]. Insufficient penetration of the embolic material frequently resultsin recanalization of the lesion due to rich collateral vessels. Coils may be used asan adjunct agent in NBCA embolization to protect normal territory or may beused as a primary agent for high-flow AVFs. Particles are not used because theirocclusive effect tends to be temporary, resulting in a higher rate of recanalization.

The pretherapeutic angiographic protocol for these lesions is similar to thatfor tumors except that evaluation of the venous drainage is more important.Angiograms of the bilateral segmental arteries should be obtained at the level of thefeeders as well as at least two levels above and below the level of the malformation.If there is intradural venous drainage to the perimedullary veins, it is essentialto evaluate the circulation time of the ASA. For this purpose, an angiogram ofthe dominant radiculomedullary artery (frequently Adamkiewicz’s artery)should be obtained by injecting a large amount of contrast material with a longimaging time (e.g., 10 cc of contrast injected at a rate of 1 cc/s, imaging time40–60 s). If the circulation time of the ASA is prolonged with no opacificationof the spinal cord venous drainage, this indicates the existence of spinal cordvenous hypertension and explains the most likely etiology of the patient’s neu-rological deficits. Spinal cord venous hypertension is the underlying cause ofalmost all SDAVFs, many perimedullary AVFs, and many epidural AVFs withintradural perimedullary venous drainage [30].

The primary role of neurophysiological monitoring for this disease group isto detect a masked spinal cord artery originating from the same pedicle as thefeeder to the malformation. If there is an ASA or a PSA originating from thesame pedicle as the feeder, endovascular embolization is contraindicated unlessvery distal advancement of the microcatheter within the feeding vessel can beobtained beyond the origin of the spinal cord artery. Provocative testing by


FIGURE 6.4 A 48-year-old man with a cervical spine hemangiopericytoma. (A) Right dorsocer-vical artery angiogram on the PA view demonstrating a hypervascular tumor stain in the right C6hemivertebra. No definite spinal cord artery is identified on this study. (B) Postembolization con-trol angiogram of the right dorsocervical artery demonstrating complete devascularization of thetumor stain with preservation of the anterior spinal artery (arrows). Embolization was performedusing polyvinyl alcohol (PVA) particles with assistance of one provocative testing to confirmabsence of a spinal cord artery distal to the tip of the microcatheter. (C) Left dorsocervical arteryangiogram demonstrating hypervascular tumor stain in the left C6 hemivertebra. (D) Superselec-tive angiogram from a branch of the left dorsocervical artery. The small arrow indicates the tip ofthe microcatheter, and the large arrow indicates the tip of the guiding catheter. No spinal cordartery is identified on this study. (E) Superselective angiogram of a branch of the left dorsocervicalartery during embolization using PVA particles. The medium arrow shows the tip of the micro-catheter. There is anastomotic opacification of the anterior spinal artery (small arrows) through theretrocorporeal anastomosis from left to right. Compare to Fig. 6.1B. Provocative test can be per-formed to confirm the existence of the anterior spinal artery if there is any question. The large arrowindicates the tip of the guiding catheter. (F) Postembolization control angiogram of the left dor-socervical artery demonstrating complete devascularization of the tumor. The patient was operatedon 2 days later without significant blood loss and transfusion.

138



injecting sodium Amytal and Xylocaine should be performed if there is any sus-picion of the existence of an unidentified spinal cord artery from the feedingvessel to the malformation. The necessity of provocative testing in dural/extradural lesions, however, is exceptional because, compared with tumorcases, identification of a spinal cord artery is easier because of less distortion ofthe spine and spinal cord and no overlapping abnormal vascularity or metallicdevices. Careful analysis of the vascular anatomy of the lesion and the normalspinal cord is far more important than provocative testing. Another role of neu-rophysiological monitoring is early detection of possible spinal cord ischemia.If significant changes in SEPs or MEPs are detected during embolization, theprocedure should be suspended until full recovery of SEPs and MEPs or termi-nated to minimize the permanent damage to the spinal cord.

For certain diseases, neurophysiological monitoring has another promisingbut not yet proven role: that is, the prediction of functional recovery afterembolization. Significant improvement of SEPs or MEPs after embolization isfrequently observed in diseases with neurological symptoms secondary to spinalcord venous hypertension, including SDAVFs and spinal epidural fistulas withintradural venous drainage [45]. Reduction of spinal cord venous hypertensionafter embolization is sometimes associated with improvement of SEPs andMEPs and correlated with improvement of neurological symptoms. Althoughimprovement of SEPs and MEPs after embolization is a favorable prognosticatorfor satisfactory neurological outcome in our experience, these patients will still




require intensive rehabilitation to maximize functional recovery, even if thelesion is angiographically cured. Clinical improvement typically occurs first inmotor function, followed by sensory functions, and bladder and bowel func-tions improve last, if at all. It should be noted that improvement of potentialsduring neurophysiological monitoring does not promise complete cure of thedisease or lasting remission of the symptoms. Symptomatic lesion recurrence istypically associated with deterioration of the neurophysiological findings. There-fore, correlation of neurophysiological improvement (SEPs and MEPs) withangiographic cure of the lesion (i.e., penetration of the embolic material into thevenous side) is important for predicting permanent clinical improvement. Fur-ther accumulation of cases with detailed analysis and long-term follow-up isnecessary to establish the exact role of neurophysiological monitoring as a pre-dictor of functional recovery after endovascular treatment for these diseases.

A case of endovascular treatment of an epidural fistula with intraduralvenous drainage is presented in the video for this chapter (choose Chapter 6from the accompanying CD main menu). This patient had improvement ofMEPs and SEPs after the embolization (Fig. 6.5) with angiographic demon-stration of complete cure of the lesion and improvement of spinal cord venoushypertension. The patient experienced immediate clinical improvement afterthe embolization and was neurologically intact at the 3-month follow-up.

3.4.2.2 Intradural Vascular Malformations

Intradural vascular malformations are further classified into spinal cord AVMsor AVFs, telangiectasias, and cavernous malformations. Endovascular embo-lization is indicated and is the first choice of treatment for spinal cord AVMsand AVFs. Embolization is usually curative for simple AVMs and AVFs, but pal-liative or rarely curative for complex or extensive AVMs. Palliative embolizationis targeted to occlude dangerous structures such as aneurysms or high-flow fis-tulas and is performed to decrease the risk of hemorrhage or to improve neu-rological symptoms. Endovascular treatment for this disease group isconsidered as high risk because embolization is performed through the ASAs orPSAs that supply the normal spinal cord as well as the lesion. A liquid embolicagent, such as NBCA, is preferred for nidus AVMs and small fistulas because ofits ability to penetrate distally and cause permanent occlusion. For large fistu-las and associated aneurysms, coils are also effective. Particles are used mainlyfor small AVMs or AVFs for which distal catheterization through the feeder isdifficult [25, 45, 68–70].

Neurophysiological monitoring, including provocative testing, is mostimportant in this disease category because of the high-risk nature of the treat-ment. The main role of this monitoring is early detection of spinal cord ischemiaby continuous monitoring of SEPs, MEPs, and BCRs, and prediction of the safetyof embolization from a certain microcatheter position by provocative testing.



Spinal cord ischemia due to compromised spinal cord vascular supply duringthe procedure can occur not only by injection of embolic agents but also bycatheterization of a feeder, either from blockage of the flow by the catheteritself, or spasm or dissection created by catheter manipulation [47]. An exam-ple of early detection of compromised spinal cord vascular supply by MEP mon-itoring and its treatment is demonstrated in Fig. 6.6.

FIGURE 6.5 A 23-year-old woman presented with progressive bilateral lower extremity weakness,numbness, and bladder and bowel dysfunction. The angiography and embolization procedure ofthis patient is presented in the video (choose Chapter 6 from the accompanying CD main menu).(A) SEPs from the bilateral posterior tibialis nerve (PTN) before (OP) and after (CL) embolizationprocedure, demonstrating significant improvement of the latency of the response. (B) MEPs fromthe bilateral abductor hallucis muscles (AH) before (OP) and after (CL) the embolization proce-dure, demonstrating significant improvement of the latency of the response. These figures demon-strate neurophysiological evidence of improvement of the spinal cord venous hypertension.


FIGURE 6.6 A 28-year-old man presented with progressive weakness and numbness of both lowerextremities and bladder dysfunction. (A) Left, normal MEPs recorded from the left tibialis anterior(TA) muscle. Right, left T11 intercostal angiogram showing an intramedullary AVM (arrows) suppliedby the anterior spinal artery (ASA, arrowheads). (B) Left, disappearance of MEPs from the left TAmuscle during superselective catheterization of the ASA. Middle, complete flow arrest in the ASA(arrowheads) distal to the tip of the microcatheter (arrow) was noted. Right, nonsubtracted imagedemonstrating opened hairpin loop of the radiculomedullary artery (arrowheads) by the micro-catheter. (C) Following quick particle embolization of the AVM, the microcatheter was removed withtemporary partial improvement of MEPs and flow in the ASA. Left, a few minutes later, the MEPs fromthe left TA muscle completely disappeared. Right, left T11 angiogram demonstrating no opacificationof the ASA due to severe vasospasm. (D) This was treated by superselective infusion of papaverineinto the radiculomedullary artery. Left, complete recovery of MEPs after papaverine infusion. Right,complete resolution of vasospasm with opacification of the normal ASA and minimal opacification ofthe remaining AVM after embolization. Modified from [47].

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FIGURE 6.6 (Continued).

143



FIGURE 6.7 A 46-year-old man presented with progressive paraparesis, urinary and fecal incon-tinence, and associated lower back pain. (A) Right L2 lumbar artery angiogram demonstrating anintramedullary arteriovenous malformation (AVM) supplied by the posterior spinal artery (PSA,arrowheads). This was superselectively catheterized for embolization. (B) Superselective angiogramof the right PSA showing the AVM. No normal spinal cord supply is identified on this study. Thearrow indicates the tip of the microcatheter. Provocative testing from this catheter position was pos-itive with disappearance of SEPs from the right posterior tibialis nerve (PTN). Repeat testing wasalso positive, and saline injection from the same catheter position did not cause any change in SEPs.See G. (C) Superselective angiogram of the right PSA from the further advanced microcatheter(arrow), demonstrating the distal portion of the AVM as well as normal PSA on both sides (smallarrowheads). There is also anastomotic opacification of the ASA (curved arrow) with deviation ofits proximal portion (large arrowheads) due to the AVM. (D) Nonsubtracted image demonstratinga microcoil placed to protect the distal normal PSA (arrows). The large arrow indicates the tip ofthe microcatheter, which was brought back after placement of the microcoil. The arrowheads indi-cate NBCA cast due to prior embolization from the ASA. (E) Superselective angiogram of the PSArepeated from the catheter position in D. Repeat provocative testing was negative (see G), andembolization using NBCA was performed from this catheter position. (F) Postembolization controlangiogram of the right T11 intercostal artery demonstrating small residual nidus of the AVM. Theright PSA distal to the AVM (arrows) is supplied by anastomotic vessels (arrowheads) from the leftPSA. No change in SEPs was seen after the embolization. See G. (G) Trace of the provocative test-ing using Xylocaine and SEPs from the right PTN. The patient was neurologically unchanged afterthe embolization. Modified from [48].









In the rare situation in which the vascular anatomy of the lesion is so com-plicated that it is difficult to differentiate feeders to the malformation from thenormal spinal cord supply, provocative testing can be used as an aid for analy-sis of the vascular anatomy. It should be emphasized, however, that the avail-ability of provocative testing does not decrease the importance of preciseangiographic analysis of the vascular anatomy of the malformation and sur-rounding normal spinal cord. The correlation between clinical improvement andimprovement of MEPs or SEPs after embolization of intradural AVFs and AVMsremains to be elucidated [48], and further accumulation of experience is needed.Figure 6.7 shows an example of a spinal cord AVM embolization using neuro-physiological monitoring and provocative testing.

4 CONCLUSIONS

To date, neurophysiological monitoring is feasible in the great majority of patientsundergoing endovascular procedures for spine or spinal cord lesions. MuscleMEPs and SEPs retain their own specificity in assessing the functional integrityof motor and sensory pathways, respectively. To rely solely on either one ofthese monitoring modalities is not supported from a scientific background orjustified from a clinical perspective. Provocative tests with both Amytal andXylocaine are mandatory in selecting those patients amenable to a safe embo-lization. Neurophysiological monitoring during endovascular procedures offersa unique opportunity to investigate the spinal cord hemodynamic and to inte-grate functional, anatomical, and clinical data. Included with the accompany-ing CD is a video showing an angioembolization of an epidural fistula of thespinal cord (choose Chapter 6 from the main CD menu).

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FIGURE 6.1 Schematic representation of spinal vascular anatomy and its relationship with long tracts involved in the generation of somatosensory and motor evoked potentials. 1. Posterior spinal arteries. 2. Posterior spinal vein. 3. Anterior spinal artery. 4. Anterior spinal vein. 5. Spinal ventral roots. 6. Anterior corticospinal tracts. 7. Lateral corticospinal tracts. 8. Dorsal columns. (Modified from Nieuwenhuys, R., Voogd, J., and van Huijzen, C. (1988). The human central nervous system: A synopsis and atlas, rev. ed. 3. Springer Verlag, Berlin).

C H A P T E R 7

IntraoperativeNeurophysiologicalMapping of the SpinalCord’s Dorsal ColumnsMATEVZ J. KRZAN

Department of Neurology, Children’s Hospital, University Medical Center, Ljubljana, Slovenia

1 Introduction1.1 Neurophysiological Generators of SEPs

in the Spinal Cord2 Methods of Intraoperative Recording of SEPs

with Miniature Electrodes2.1 Recording of SEPs with a Miniature Multielectrode

3 Results4 Discussion5 ConclusionReferences

ABSTRACT

Intramedullary lesions distort the anatomical features of the spinal cord dorsum,making it difficult for the surgeon to perform a myelotomy precisely at the midline.Myelotomies not performed at the midline may damage the dorsal columns. To helpestablish neurophysiological landmarks on the dorsal cord surface to compensatefor distorted anatomy and provide reliable guidance, a highly selective miniaturemapping multielectrode was placed on the exposed dorsal cord surface in patientsundergoing resection of intramedullary lesions. This miniature electrode recordssomatosensory evoked potentials (SEPs) after tibial and median nerve stimulation.The electrode consists of eight parallel wires spaced 1 mm apart, each having a diam-eter of 76 µm and an exposed recording surface of 2 mm. After each of the tibialnerves at the ankles was electrically stimulated, SEPs were recorded with the minia-ture electrode separately from each of the eight parallel recording sites with a refer-ence needle electrode placed in nearby muscle. Recordings were obtained in 55



154 Matevz J. Krzan

patients and revealed an amplitude gradient across the eight recording sites with max-imum amplitude toward the midline and decreasing amplitude toward the dorsal rootentry zone. SEPs consisted of multispike activity lasting about 10 ms with mean ampli-tudes ranging from 0.7 to 43 µV. SEPs recorded over the cervical spinal cord aftermedian nerve stimulation showed an amplitude gradient as well, but in the oppositedirection of the tibial nerve SEPs. For median nerve SEPs, the site with the highestamplitude was always lateral to the site with the highest amplitude of SEPs after tibialnerve stimulation. The two recording sites with highest-amplitude SEPs after stimula-tion of either left or right tibial nerve identified the neurophysiological midline betweenthe dorsal columns. In the patients in whom the anatomy had not been distorted, theneurophysiological midline corresponded with the anatomical one.

1 INTRODUCTION

Lesions to nervous structures induced during surgery can be avoided using intra-operative neurophysiological techniques [1]. Mapping techniques, in contrast tothose applied for continuous monitoring, are used to neurophysiologically locatespecific structures in the nervous system but not to continuously monitor theirfunctional integrity. They have been applied to map different parts of the humannervous system at critical periods of surgical procedures, usually before incisionplacement or lesioning, in order to confirm anatomical structures or to give guid-ance when anatomical landmarks are distorted or nonexistent [2].

Some of the more frequently applied intraoperative mapping techniquesinclude phase reversal of the median nerve somatosensory evoked potentials(SEPs) [3] and exposed motor cortex stimulation [4] to locate the primary sen-sory and motor cortices, mapping of the cranial nerve motor nuclei within thebrainstem [5], mapping of the dorsal root entry zone (DREZ) in the spinal cord[6], mapping of pudendal afferents and lumbosacral efferents [2, 7], andbrachial plexus mapping [8].

Spinal intramedullary lesions are surgically approached by entering thespinal cord in the midline at the posterior median sulcus between the left andright dorsal columns. Anatomical features of the exposed spinal cord can oftenbe distorted, making it difficult for the surgeon to choose the optimal incisionplacement. Severing dorsal column pathways can lead to serious postopera-tive neurological impairment (e.g., ataxia or sensory loss). With continuousintraoperative recording of SEPs, such lesioning can be documented but notprevented [2, 9].

In a series of 35 patients undergoing resection of intramedullary lesions at theInstitute for Neurology and Neurosurgery, Beth Israel Hospital in New York, SEPrecordings were lost early in the course of resection in 20 (57%), indicating alesion of the dorsal columns during placement of the initial incision into thespinal cord (myelotomy) [10].


Intraoperative Neurophysiological Mapping of the Spinal Cord’s Dorsal Columns 155

1.1 NEUROPHYSIOLOGICAL GENERATORS

OF SEPS IN THE SPINAL CORD

On the surface of the spinal cord, conducted and segmental evoked potentialscan be easily distinguished after stimulation of peripheral nerves or roots[11].

1.1.1 Conducted Potentials

Conducted spinal evoked potentials recorded from the dorsal pial cord surfaceconsist primarily of negative waves reflecting the compound action potentialstraveling in the dorsal column fibers. Their amplitudes diminish from caudal torostral recording sites due to dispersion of the afferent volleys caused by dif-ferent conduction velocities among various fibers, but are not significantlyreduced at higher stimulation frequencies. When recorded from the ventral pialcord surface, their polarity is unchanged, suggesting that a generator is ori-ented along the longitudinal axis of the cord, with the negative pole placed cau-dally and the positive pole placed cranially [11–13].

1.1.2 Segmental Potentials

Segmental potentials represent the summated activity of cells of the spinalcord’s grey matter with intermixed rootlet activity. They have a maximumamplitude at the levels corresponding to the cord entry of the stimulated nervefibers and decrease caudally and cranially [14, 15]. Following the electricalstimulus, the afferent compound action potential of the dorsal root fibers isrecorded as a fast, predominantly positive wave (P1) on the dorsal surface of theexposed spinal cord. This is predominantly generated by fast-conducting Aβand Aγ fibers, and its amplitude is not reduced by high-frequency stimulation[15]. A negative wave (N1) representing postsynaptic potentials generated inthe dorsal horn neurons of the spinal cord follows. It has a longer durationthan the previous one because of repetitive firing and relaying of neurons in thedorsal horns and is reduced by high-frequency stimulation. A low-voltage, slowpositive wave (P2) that reflects depolarization of afferent fiber terminals follows[13–15].

When recorded from the ventral cord surface, segmental potentials invertpolarity, since their generator dipoles are placed in the sagittal plane [16]. Afterstimulation of median/ulnar or tibial nerves, the segmental responses areP9/N13 or P17/N22, respectively [14].


156 Matevz J. Krzan

2 METHODS OF INTRAOPERATIVERECORDING OF SEPs WITH MINIATURE ELECTRODES

Intraoperative recordings from the exposed surface of the human spinal cord werefirst reported during surgical ablative procedures for relief of chronic pain [6, 11,16]. Silver ball [11] or stainless steel disc electrodes [17] were used to record spinalresponses after peripheral nerve stimulation. Segmental responses were recordedrostrally and caudally to identify the DREZ for lesioning. Jeanmonod et al. [11]also reported intraoperative recordings of conducted potentials with the ball elec-trode on the dorsal columns rostral to the surgical site. They were used for moni-toring in order to avoid lesioning the dorsal columns, but not for mappingpurposes [16].

2.1 RECORDING OF SEPS WITH A MINIATURE

MULTIELECTRODE

In order to be able to offer guidance to surgeons in performing myelotomy inthe midline, we attempted to identify neurophysiological features on the exposeddorsal cord surface using conducted potentials. Prior to myelotomy, the sur-geon placed a miniature multielectrode on the exposed dorsal cord surfaceapproximately at the midline and according to available anatomical landmarks(choose Chapter 7 from the accompanying CD’s main menu to see a short videoof this procedure). This multielectrode is highly selective for recording spinalSEPs from the dorsal surface of the exposed spinal cord [18].

A specially designed miniature multielectrode consisting of 8 parallelTeflon-coated stainless steel wires (with a diameter of 76 µm spaced 1 mmapart) embedded in silastic was used. Each wire was stripped of its coatingalong a length of 2 mm. The recording wires ran parallel to the long axis of thespinal cord, and the reference needle electrode was placed in nearby muscle.The impedance for all recording surfaces was about 20 kΩ, the filter settingswere 50–1700 Hz, and the epoch length was 20 ms. To ensure reproducibility,two sets of 100 sweeps were averaged from each of the eight parallel record-ing surfaces after stimulation of each tibial nerve at the ankle (or median nerveat the wrist). The stimulus intensity was 40 mA or lower, stimulus durationwas 0.2 ms, and the repetition rate of the stimulation was 13.3 Hz. Patientswere anesthetized using a continuous intravenous infusion of propofol andfentanyl with addition of N2O. In 65 patients studied, 56 patients had tumors(ependymomas, astrocytomas, vascular tumors, lipomas, metastases, etc.),7 patients had syrinxes, and 2 patients had inflammatory lesions. The lesion



was located in the cervical spinal cord in 46 patients, 17 patients had lesionsin the thoracic spinal cord, and 2 patients had lesions in the lumbar sectionsof the spinal cord.

3 RESULTS

We obtained reproducible spinal SEPs in 55 of the 65 patients, aged 7–66 years,before myelotomy was performed. In 10 patients reproducible spinal SEPscould not be obtained because of anatomical (large lesion protruding to thecord surface, previous surgery producing adhesions), physiological (low ampli-tude and inconsistent responses, segmental wave contamination at the lumbarlevel), or technical factors. In patients in whom anatomical factors preventedrecordings, the responses could usually be recorded caudally to the site of thelesion.

The recordings from each of the eight parallel electrode surfaces resembledconducted spinal SEPs previously detected with the silver ball electrode orconventional epidural electrodes [11, 12, 13]. They consisted of multispikeactivity lasting about 10 ms with mean amplitudes ranging from 0.7 to 43 µV.An amplitude gradient of SEPs across different electrode recording sites wasobserved. For tibial nerve SEPs, the maximum amplitude was toward the mid-line and decreased toward the DREZ. The neurophysiological or functionalmidline was determined to lie between the two recording sites, with highestSEP amplitudes after stimulation of either left or right tibial nerve (Fig. 7.1)(see also color plate). In one patient we recorded conducted responses usingtwo recording methods: in monopolar fashion (needle electrode versus each ofthe eight recording surfaces) as well as in bipolar fashion using differentialrecordings (recording surfaces 1–2, or 2–3, or 3–4, etc.) (Fig. 7.2). In 3 patients,spinal SEPs were obtained with the electrode turned at a right angle so thatthe recording wires were perpendicular to the cord axis and the direction ofthe fibers in the dorsal column (orthogonal position) (Fig. 7.3). In theserecordings, no amplitude gradient was seen across the eight electrode sur-faces. A slight latency shift from the caudal to the cranial electrode enabledthe calculation of conduction velocities for some of the most prominentpeaks, having a value of 45 m/s.

In patients with cervical lesions, we also recorded spinal SEPs aftermedian nerve stimulation. The recorded potentials consisted mainly of seg-mental responses. An amplitude gradient across eight recording sites wasalso observed, with highest amplitudes of SEPs laterally, close to the DREZ.Lower amplitudes were observed toward the dorsal midline (Fig. 7.4). Thisis the opposite of what was observed for recorded SEPs following tibial nervestimulation.


158

FIGURE 7.1 Dorsal column mapping in a 58-year-old patient with an inflammatory lesion between the C2 and C6 segments of the spinal cord. SpinalSEP responses were obtained from the eight recording sites after left and right tibial nerve stimulation. Two sets of 100 sweeps were averaged. Note theamplitude gradient across the recording surfaces. Maximum amplitude after left-sided stimulation occurred at recording site 6, and right-sided stimulationproduced the maximum amplitude at recording site 4. Between the traces is an intraoperative picture taken during the measurement. Above, schematic crosssection of the cervical spinal cord showing the approximate position of the recording electrode, with the dorsal column midline under recording site 5 (seealso color plate).


159

FIGURE 7.2 Spinal SEP responses obtained at the eight recording surfaces using monopolar (left) and bipolar (right) montage after stimulation of thesame tibial nerve. Note that the highest amplitude in the responses on the left is at the identical recording site as the phase reversal for the responses onthe right.


160 Matevz J. Krzan

4 DISCUSSION

Our continuous involvement with intramedullary surgery has prompted us tolook for new methods in preventing intraoperative injury to the dorsal columnsof the spinal cord. The posterior funiculi of the spinal cord are at high risk fordamage during these procedures because the approach to deeper-lying lesionsoften leads through the dorsal columns.

In all patients undergoing spinal cord surgery, routine multimodal neuro-physiological monitoring including tibial and median nerve SEPs is used. SinceSEP signals pass through the dorsal columns, we use them for mapping purposesin addition to continuous monitoring. In the cervical spinal cord, the fibers fromthe lower extremities that convey tibial nerve SEPs are situated in the ipsilateralfasciculus gracilis (i.e., medially), and those conveying median nerve SEPs aremore lateral in the ipsilateral cuneate fascicle [11, 14]. With the multielectrodeplaced on the dorsal cord surface, we recorded repeatable, conducted waves aftertibial nerve stimulation. The spinal SEPs showed an amplitude gradient ipsilat-eral to the stimulated side, with the highest amplitude of SEPs at a single elec-trode contact for each stimulated tibial nerve (Figs. 7.1 and 7.4) (see also colorplate). Spinal SEPs after median nerve stimulation recorded with the miniaturemultielectrode represent mainly dorsal horn activity (segmental potentials)with a small superposition of conducted potentials. Because the dorsal horns are

FIGURE 7.3 Spinal SEP responses obtained at the eight recording sites with the electrode record-ing surfaces orthogonal to the long spinal cord axis. No amplitude gradient was observed. Theenlarged segment of the SEP (between 28 and 32 ms) showed slight changes in latency betweenrecording sites 1 and 8.


161

FIGURE 7.4 Dorsal column mapping in a 43-year-old patient with an ependymoma between the C1 and C7 segments of the spinal cord. Spinal SEPresponses were obtained from the eight recording sites after left and right tibial (bottom 2 traces) and median nerve (top 2 traces) stimulation. Two setsof 100 sweeps were averaged. Note the amplitude gradient of conducted potentials across the recording surfaces, with maximum amplitude after left tibialstimulation at recording site 4, whereas after right-sided stimulation it was at recording site 6. There is also an amplitude gradient of segmental potentialsacross the recording sites after median stimulation. The maximum amplitude after left-sided stimulation was at recording site 1, and after right-sided stim-ulation it was at site 7. Between the traces is an intraoperative picture taken during the measurement (see also color plate).


162 Matevz J. Krzan

laterally positioned, recorded segmental potentials still showed an amplitudegradient, having maximal amplitude laterally.

In 1 patient, we recorded conducted responses in monopolar as well as bipo-lar fashion. The site with the highest amplitude, recorded monopolarly, showedphase reversal in the bipolar recording, demonstrating the high selectivity of themapping multielectrode (Fig. 7.2).

Contamination of recordings by activity originating from ipsilateral spino-cerebellar tracts situated in the lateral columns is very unlikely because (1) thetibial nerves were stimulated at the ankles, where, according to the literature,fibers contributing to the spinocerebellar pathways are relatively rare [19];(2) the DREZ separates the electrical activity of the dorsal columns from thatof the dorsolateral columns; and (3) more laterally situated recording sites,although being closer to the spinocerebellar pathways, showed lower amplitudeactivity when compared to sites closer to the dorsal midline.

We recorded spinal SEPs in 3 patients with the electrode positioned at a rightangle to the cord axis (Fig. 7.3). In this position no amplitude gradient was recorded,but a stepwise increase in latency toward the proximal electrodes was observed.

The miniature multielectrode was found to reliably record high-quality andhigh-amplitude tibial nerve spinal SEPs over the cervical and thoracic spinalcord. The electrode size was appropriate to the size of the dorsal columnsaccording to anatomical studies that showed the distance between DREZs to be6 to 7 mm at the cervical level [20]. In the lumbar area there was contamina-tion with the higher-amplitude segmental responses arising from activity in thedorsal roots and horns. Even with the hi-pass filter set at 100 Hz, we were notable to clearly distinguish conducted waves from the segmental ones. In thisarea the dorsal columns are also narrower, making positioning of the electrodemore difficult. Similar contamination with segmental waves was experienced inthe cervical area with spinal SEPs recorded after median nerve stimulation. Thiswas only helpful in determining the functional midline indirectly, indicatingproximity to the DREZ. Therefore, it can be useful in mapping of the DREZ.Nevertheless, the midline in the cervical spinal cord could successfully be deter-mined using tibial nerve SEPs.

Besides showing that measurements of SEP amplitude gradients were possi-ble intraoperatively, we were also able to identify the functional midlinebetween left and right dorsal columns in 55 of 65 patients in whom mappingwas attempted. We found this midline to lie between two recording sites withthe highest SEP amplitudes after right or left tibial nerve stimulation. In patientsin whom the anatomical midline was clearly delineated, it corresponded withthe functional midline.

Figure 7.5 (see also color plate) depicts the practical aspects of dorsal columnmapping as used to guide the surgeon in performing the myelotomy on a patient witha cervical syringomyelic cyst. According to the mapping results, the patient’s left andright dorsal columns have been shifted to the right side within the spinal cord.


163

FIGURE 7.5 Dorsal column mapping in an 18-year-old patient with a syringomyelic cyst between the C2 and C7 segments of the spinal cord. Upper right,MRI showing syrinx. Lower middle, placement of miniature electrode over surgically exposed dorsal column; vertical bars on the electrode represent thelocation of the underlying exposed electrode surfaces. SEPs after stimulation of the left and right tibial nerves showing maximum amplitude between record-ing sites 1 and 2 (lower left and right). These data strongly indicate that both dorsal columns from the left and right lower extremities have been pushed tothe extreme right side of the spinal cord. Using these data as a guideline, the surgeon performed the myelotomy through the left side of the spinal cord(upper middle) and inserted the shunt to drain the cyst. Postoperatively, the patient did not suffer from a sensory deficit. Reprinted from [1] (see also colorplate).


164 Matevz J. Krzan

5 CONCLUSION

In the nondistorted anatomy of the spinal cord dorsum, the determination of themidline in order to perform a midline myelotomy could be done on the basis ofanatomical landmarks alone. Because of pathology, the anatomical landmarks ofthe spinal cord dorsum are often not visible, and the anatomy of the spinal cordcan be changed. This makes midline myelotomy difficult to perform, increasingthe risk of postoperative sensory deficits for the patient. The dorsal column map-ping technique is a promising tool as a guide to determine the midline whenanatomical landmarks are distorted. The method is also a powerful research toolfor the study of human spinal cord physiology, offering new possibilities for fur-ther improvement of mapping and monitoring methodology.

Included with the accompanying CD is a video demonstrating the utility ofdorsal column mapping in locating the physiological midline of the dorsal columnsduring surgery on the cervical spinal cord for removal of an intramedullary tumor(choose Chapter 7 from the accompanying CD’s main menu).

REFERENCES

1. Deletis, V., and Sala, F. (2001). The role of intraoperative neurophysiology in the protectionor documentation of surgically induced injury to the spinal cord. In “Neuroprotective agents.Fifth International Conference” (W. Slikker, Jr., and W. Trembly, eds.), vol. 939, pp. 137–144.New York Academy of Science, New York.

2. Deletis, V. (1994). Evoked potentials. In “Clinical monitoring for anesthesia and critical care”(C.L. Lake, ed.), pp. 288–314. W.B. Saunders, Philadelphia.

3. Wood, C.C., Spencer, D.D., Allison, T., McGarthy, G., Williamson, V.D., and Goff, W.R.(1988). Localization of human sensorymotor cortex during surgery by cortical surface record-ing of somatosensory evoked potentials. J. Neurosurg., 68, 99–111.

4. Taniguchi, M., Cedzich, C., and Schramm, J. (1993). Modification of cortical stimulation for motorevoked potentials under general anesthesia: Technical description. Neurosurgery, 32(2), 219–226.

5. Morota, N., Deletis, V., Epstein, F., Kofler, M., Abbott, R., Lee, M., and Ruskin, K. (1996). Brainstem mapping: Neurophysiological localization of motor nuclei on the floor of the fourth ven-tricle. Neurosurgery, 37(5), 922–930.

6. Campbell, J.A., and Miles, J. (1984). Evoked potentials as an aid to lesion making in the dorsalroot entry zone. Neurosurgery, 15(6), 951–952.

7. Deletis, V., Vodusek, D., Abbott, I.R., Epstein, F.J., and Turndorf, H. (1992). Intraoperativemonitoring of the dorsal sacral roots. Minimizing the risk of iatrogenic micturition disorders.Neurosurgery, 30(1), 72–75.

8. Deletis, V., Morota, N., and Abbott, I.R. (1995). Electrodiagnosis in the management of brachialplexus surgery. In “Hand clinics: Brachial plexus surgery” (J.A. Grossman, ed.), vol. 11(4), pp.555–561. W.B. Saunders, Philadelphia.

9. Young, W. (1991). Neurophysiology of spinal cord injury. In “Spinal trauma” (T.J. Errico, R.Bauer, and T. Waugh, eds.), pp. 377–414. Lippincott, Philadelphia.

10. Kothbauer, K., and Deletis, V. (1997). Comparison of motor and sensory evoked potentialmonitoring in surgery of intramedullary tumors. Invited lecture, annual meeting of the Amer-ican Academy of Clinical Neurophysiology, Jan 29, 1997, San Francisco, CA.



11. Jeanmonod, D., Sindou, M., and Mauguiere, F. (1989). Three transverse dipolar generators inthe human cervical and lumbo-sacral dorsal horn: Evidence from direct intraoperative record-ings on the spinal cord surface. Electroencephalogr. Clin. Neurophysiol., 74, 236–240.

12. Ertekin, C. (1976). Studies on the human evoked electrospinogram: II. The conduction veloc-ity along the dorsal funiculus. Acta. Neurol. Scand., 53, 21–38.

13. Halter, J.A. (1995). Spinal cord evoked potentials recorded at different vertebral levels. In “Atlasof human spinal cord evoked potentials” (M.R. Dimitrijevic, and J.A. Halter, eds.), pp. 39–83.Butterworth-Heinemann, Boston.

14. Desmedt, J.E. (1989). Somatosensory evoked potentials in neuromonitoring. In “Neuromoni-toring in surgery” (J.E. Desmedt, ed.), pp. 1–21. Elsevier, Amsterdam.

15. Shimoji, K. (1995). Origins and properties of spinal cord evoked potentials. In “Atlas of humanspinal cord evoked potentials” (M.R. Dimitrijevic, and J.A. Halter, eds.), pp. 1–25. Butterworth-Heinemann, Boston.

16. Turano, G., Sindou, M., and Mauguiere, F. (1995). Spinal cord evoked potential monitoringduring spinal surgery for pain and spasticity. In “Atlas of human spinal cord evoked potentials”(M.R. Dimitrijevic, and J.A. Halter, eds.), pp. 107–122. Butterworth-Heinemann, Boston.

17. Nashold, B.S. Jr., Ovelmen-Levitt, J., Sharpe, R., and Higgins, A. (1985). Intraoperative evokedpotentials recorded in man directly from dorsal roots and spinal cord. J. Neurosurg., 62,680–693.

18. Krzan, M., Deletis, V., and Isgum, V. (1997). Intraoperative neurophysiological mapping ofdorsal columns: A new tool in the prevention of surgically induced sensory deficit? Electroen-cephalogr. Clin. Neurophysiol., 102, 37P.

19. Halonen, J.P., Jones, S.J., Edgar, M.A., and Ransford, A.O. (1989). Conduction properties ofepidurally recorded spinal cord potentials following lower limb stimulation in man. Electroen-cephalogr. Clin. Neurophysiol., 74, 161–174.

20. Smith, M., and Deacon, P. (1984). Topographical anatomy of the posterior columns of thespinal cord in man: The long ascending fibres. Brain, 107, 671–698.


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C H A P T E R 8

IntraoperativeNeurophysiology of thePeripheral Nervous SystemLEO HAPPEL AND DAVID KLINE

Louisiana State University Medical Center, New Orleans, Louisiana

1 Background2 Nerve Regeneration3 Equipment for Intraoperative Recording4 Electrodes for Intraoperative Recording

and Stimulation5 Anesthetic Considerations6 Recording CNAPs Intraoperatively7 Criteria for Appraising a CNAP8 Operative Results9 Troubleshooting


ABSTRACT

Intraoperative recordings of compound nerve action potentials (CNAPs) can providequick, reliable information on the status of peripheral nerves at the time of surgery.The technique is straightforward and can be easily used by those without a lot of pre-vious experience in monitoring peripheral nerves. It requires no unusual instru-mentation and is very cost-effective. It does not compromise routine surgicalexploration of a peripheral nerve injury. The information provided by these studiesis very useful in determining the best course of action to deal with a particularperipheral nerve injury. The indications of early, successful peripheral nerve regen-eration observed in these studies cannot be obtained in any other way. Thus themethod should not be viewed as a “monitor” of peripheral nerve activity—the infor-mation is diagnostic and essential. We encourage the use of this technique as a meansof evaluating a peripheral nerve injury and deciding on the best way to deal with it.To facilitate the application of intraoperative recordings, this chapter will include adescription of the methodology, an interpretation of the findings of intraoperative



170 Leo Happel and David Kline

recordings, some background in the pathophysiology of nerve injury and regenera-tion, and a practical section on troubleshooting to assist those who are just begin-ning to use this technique.

1 BACKGROUND

The surgeon confronted by a neuroma in continuity has difficult decisions tomake. He must determine the status of the nerve at the time of surgery andjudge its potential to recover from injury. He must decide the best course ofaction to give the injured nerve the best prospect for an optimal recovery.Although pathologic examination can provide anatomical information on thestatus of the nerve, this information is not available without removing a speci-men. This may further damage a nerve already undergoing regeneration and isnot a reasonable solution. Few studies have focused on the functional status ofthe nerve. Over the course of three and a half decades, we have explored the useof operative peripheral nerve recordings to facilitate the process of decisionmaking during exploration and repair of a peripheral nerve injury [1]. Thecompound nerve action potential (CNAP) has been found to be a useful tooltoward this goal [1–7].

Some background knowledge on the response of nerves to injury is necessaryto understand the findings of these neurophysiological studies. One objective ofthis chapter will be to describe the changes that occur in injured nerves and torelate these to the process of regeneration in order to gain insight into the inter-pretation of intraoperative neurophysiological studies. The technical difficultiesassociated with recording nerve action potentials often prevent those with littleexperience from obtaining useful recordings. Therefore, another objective will beto guide the reader with a detailed technical background. These technical issuesmay seem needlessly complex at times, but it is hoped that they may serve as areference to address specific problems that may arise as one gains experience.

A nerve lesion that leaves the nerve in some degree of continuity may affectsome parts of the nerve more than others. Though it may be misleading, theterm partial nerve injury is often applied in this circumstance. The use of thisterm seems to imply that some parts of the nerve fibers remain normal whileother parts are affected by injury. In such a lesion it is more realistic to hold theposition that none of the nerve is normal but some portions are more severelyaffected than others [5, 8]. Perhaps a better term for this situation would be amixed injury to the nerve. Often, some parts of the nerve can be treated differ-ently to improve prospects for recovery. Some fascicles can be resected andrepaired, and others can simply be neurolysed. In this “split repair,” those por-tions of the nerve that are minimally influenced by the surgeon will show a fasterfunctional recovery than those that had to be resected and repaired. Thus they


Intraoperative Neurophysiology of the Peripheral Nervous System 171

will also ultimately regenerate more effectively. Most injuries that are severeand yet leave the nerve in continuity affect in similar fashion the whole crosssection of the nerve. However, some of these nerves have the ability to regen-erate well and others do not. Operative nerve recording are equally importantin these instances [8–10].

When some fascicles contain axons that are interrupted and others containintact axons, a neuroma in continuity may develop in part of the nerve. Thisoccurs as regrowing axons fail to project in length and fold back onto them-selves. The entangled, growing neurites increase in volume and begin to com-press the intact axons. This results in a progressive loss of function long afterthe initial insult to the nerve. We have seen many examples of large neuromasin continuity, such as that seen in Fig. 8.1B, with significant portions of thenerve still showing conduction. Operative recordings, then, have accuratelyshown that the proper course of surgical treatment is to do a split repair, resect-ing only those fascicles involved in a neuroma and sparing those that remainintact. This ensures that the patient will have the best outcome for the injuryhe or she has sustained.

Similarly, as in Fig. 8.1A, we have seen many examples of lesions that arebenign in appearance but that show no electrical conduction. Visual inspectionalone might deceive the surgeon, suggesting that this lesion might regeneratewithout repair. In most cases such a severe lesion will not show significantregeneration, and the best course of action would be to resect and repair it.

At the time of surgery the objective is to put neurophysiological findings intothe context of patient history to gain some insight into the anatomy of the nervewithout having to biopsy it. Preoperative neurophysiological studies may behelpful in describing the lesion, though these studies should not be done within72 hr of injury. Within this 72 hr time period, axons distal to the point of injurymay survive even if they are completely transected and may subsequently pro-vide misleading information [5, 8, 11]. If the surgery is a primary repair per-formed within 72 hr of injury, preoperative neurophysiological studies may notbe helpful. If the nerve is bluntly and completely transected, a delayed earlyrepair may be planned at 3 weeks. Lesions in continuity, however, are more dif-ficult to deal with. In the case of a secondary repair when a lesion in continu-ity is suspected, we will usually plan surgery at approximately 2 to 4 monthspost injury. In this case, initial neurophysiological studies would be routine andwould evaluate the extent of the initial injury. They also provide a basis of com-parison for what can be seen operatively. Surgical exploration three monthsafter injury may also indicate whether spontaneous regeneration has begun.The operative electrophysiology supplements information that was learnedpreoperatively to provide a perspective of the extent of injury to the nerve.Once the extent of the injury has been determined, the optimal surgical treat-ment can be provided.



FIGURE 8.1 (A) This neuroma in continuity is small in size and appears benign. However, neu-rophysiological testing and subsequent pathological examination confirm that there were no sig-nificant axons passing through the lesion, which was properly resected and repaired. (B) This largeneuroma in continuity looked and felt as if it was simply scar tissue. CNAPs recorded across it con-firmed good conduction in many of the axons. This lesion was present in only a small part of thewhole nerve, leaving much of it spared. We conducted a “split repair,” resecting and repairing onlythe involved fascicles.



Sunderland has classified nerve injuries into five categories ranging frommild functional change to division of the nerve [8, 12]. Operative recordingscan facilitate an understanding of the degree of injury as described by Sunder-land. A Sunderland grade 1 injury that is neurapraxic leaves the axon in conti-nuity. There may be mild changes to myelin but little other anatomic change.As long as the axon remains connected to the cell body, it remains functionaleven though a localized conduction block exists at the point of injury. This canbe determined easily at the operating table by stimulating and successfullyrecording from a section of axon that is distal to the point of injury. Preopera-tive EMG would show similar findings, and the needle EMG study would showlittle or no evidence of denervation. Again, these recordings should not be madewithin 72 hr of the initial injury, for the reasons cited previously. A functionalblock of conduction at the site of injury does not affect conduction in the axondistally. A demonstration of normal nerve excitation and conduction in thenerve distal to the point of injury is proof of axonal integrity. An importantexception to this is the avulsive injury that divides the sensory axon proximalto the dorsal root ganglion but spares the distal axon in the nerve. The distalaxon would exhibit normal excitation and conduction properties, and yet itwould be disconnected from the central nervous system. Preoperative EMGstudies—as well as radiographic studies—should alert the surgeon to this pos-sibility, which should be considered in appropriate circumstances and whichwill be treated later in this chapter.

A Sunderland grade 2 injury is axonotmetic, leading to Wallerian degenera-tion of the axon distal to the point of injury. This degeneration causes the distalaxon to lose its properties of electrical excitability over the course of 72 hr. Noperipheral nerve action potential can be seen if all of the fibers of the nerveunder study have degenerated. This injury, however, is associated with littlederangement of the connective tissue elements of the nerve. Spontaneous nerveregeneration is likely with this degree of injury, and, if the timing of surgicalexploration is appropriate, early indications of axonal regeneration can be seenacross the site of injury. This is one of the great advantages of operative record-ings. Routine preoperative EMG studies would not show these early indica-tions of regeneration. The electrical characteristics of these regenerating axonsdistinguish them from normal axons, as will be discussed later.

Sunderland grade 3 and grade 4 injuries represent greater obstacles to nerveregeneration. In these cases the injury is neurotmetic, altering the connectivetissue components of the nerve. A grade 3 injury is a mix of axonotmetic andneurotmetic injuries and is associated with mild derangement of connectivetissue and mild scar formation. Examination of this injury by operative record-ings at 3 months may also show indications of early spontaneous regeneration,suggesting conservative surgical treatment. However, a grade 4 injury is neurot-metic and will be associated with much greater scar formation and a formidable



barrier to nerve regeneration. Electrical recordings performed at 3 months afterinjury would not show indications of early regeneration if this scar blocksregrowing axons. Grade 3 and grade 4 injuries are the most important to dif-ferentiate, since the heavy scar of grade 4 injury will not permit spontaneousregeneration. This lesion in continuity must be resected and repaired in orderto provide the best chance for optimal recovery and to remove the offensive scarthat blocks the regrowth of nerve [6–8].

A grade 5 injury results in a complete transection of nerve, either from a sharpor blunt insult. Blunt injuries may include those that, by stretching, pull thenerve completely apart. In both of these cases, a complete repair of the nerve isnecessary. However, with blunt injury it is often difficult to determine the lengthof injured nerve that should be removed. Operative recordings can be helpful inthis regard, demonstrating the point on the proximal stump where viable axonsremain. Then, once the nerve is sectioned at this point, one can visibly determineif a fascicular pattern remains at this level. In this way one can determinewhether the entire scar has been removed before the repair is begun [8, 13].

2 NERVE REGENERATION

In order to understand neurophysiological findings obtained during surgery, itis necessary to understand the process of nerve regeneration. This process iscomplex, and particularly so in humans. There is a significant difference in theprocesses of regeneration between lower mammals, such as the rat, and thoseprocesses in the human. In lower mammals nerve regeneration is much moreeffective and complete, so much so that in some experimental settings it evenbecomes difficult to prevent nerve regeneration. Rat nerves usually show sig-nificant regeneration even in the most adverse circumstances. By contrast,peripheral nerve regeneration in humans is not nearly so effective, and regen-erated axons never regain the electrical properties of their original counter-parts. For this reason, one needs to be particularly careful in applying theresults of research conducted on lower mammals to the human [8, 13, 14].

When an axon is divided, the distal part undergoes Wallerian degeneration[11], and the proximal part seals off at the point of division. Within 36 hr, mul-tiple sprouts of growing neurites appear at the sealed end of the proximal axon[12]. These sprouts will give rise to several small, growing axons, each attachedto the single proximal axon. The point of injury becomes a branch point, andit is not uncommon to see axon counts distal to the point of injury that arehigher than proximal axon counts. These growing axons are much smaller indiameter and have distinctive electrical properties [15–18]. Their thresholds aremarkedly higher than those of normal nerves, and they are particularly insen-sitive to short-duration stimulus pulses, in part because of the increased capac-itance of their membranes. Their conduction velocities fall into a range that is



much lower than that of normal nerve. As the process of nerve regenerationcontinues, these axon sprouts elongate. During effective regeneration, some ofthese fine fibers will eventually die back in order to allow remaining fibers toincrease in caliber [12]. If these small-diameter fibers do not increase in diam-eter, they are unlikely to form an effective junction with muscle, since motoraxons must achieve a critical diameter in order to produce a useful motor unit.Should many fine fibers persist, the motor units formed will not lead to signif-icant muscle strength [8, 12, 14, 19]. The presence of fine fibers may be an indi-cation of ongoing regeneration at a very early stage but may also indicateineffective regeneration at a later stage.

3 EQUIPMENT FOR INTRAOPERATIVE RECORDING

Operative recordings of peripheral nerve action potentials can be easily accom-plished with many types of commercially available EMG machines. These offerboth stimulating and recording capabilities that are appropriate for the opera-tive setting [20]. Evoked potential instrumentation can also be used, though itis usually more complex and difficult to use in such a simple setting. The stim-ulator used operatively should have the ability to produce pulses of short dura-tion (0.02–0.05 ms) and intensities up to 70 V. We advocate the use of veryshort duration stimulus pulses to reduce stimulus artifact. Short-duration stim-ulus pulses may also help discriminate the types of fibers that might be present, asis illustrated in Fig. 8.2. Small-diameter fibers of normal nerve are less sensitive to

FIGURE 8.2 The strength–duration relationship for stimulation shows that for normal fibersshort-duration stimulus pulses require greater intensity. This phenomenon is particularly exag-gerated at extremely short stimulus pulse durations. By comparison, regenerated axons are even lesssensitive to short-duration stimulus pulses. This principle can be used to help discriminate the qual-ities of axons found in injured nerve. By using short-duration stimulus pulses, we can selectivelyactivate larger-diameter axons. Reprinted from [5].



short-duration stimulus pulses [17]. The fine fibers of regenerating axons areeven less sensitive to short-duration pulses than are equivalent normal fibers.Their strength–duration relationship is different than that of normal fibers withsimilar size. The responses that we record to stimulation with short-durationpulses are, necessarily, from larger-diameter axons, and these may be a betterindicator of effective regeneration. Additionally, these short-duration pulsesreduce the amount of stimulus artifact; this subject will be discussed further ina later section [20].

The strength–duration relationship seen in Fig. 8.2 also shows that withshort-duration stimulus pulses much higher stimulus intensities must be used[17, 21]. We have found that in some cases when short-duration pulses areused, stimulus intensities as high as 70 V are required to excite regeneratingaxons. As long as pulse duration is kept short, these intensities can be usedsafely. However, if long-duration pulses are used at this intensity, the energiestransferred by the stimulator can become dangerous and electrical burns maybe possible. This is an additional reason for using short-duration pulses.

The stimulus should be properly isolated from ground (as illustrated inFig. 8.1) in order to prevent electrical currents from leaking into the recorderor through some other part of the patient’s body. With no stimulus isolation, apotential difference applied between stimulating electrodes also represents apotential difference with any other electrode that may be connected to ground,such as the recording electrode seen in this example. The stimulator may pro-duce a current through any other electrical contact that the patient may havewith ground. Though stimulus isolation is engineered into the EMG machine,this engineering can be defeated through poor application. If the wires leadingto the stimulating electrodes are shielded, the resulting capacitance to grounddefeats stimulus isolation and spurious currents may result. The cable con-necting stimulating electrodes to the instrumentation should not be shielded.The same process may occur if these wires are draped against a metal surfacesuch as the operating table or next to other wires. The resulting capacitive cou-pling defeats the stimulus isolation engineered into the EMG machine. Thismay produce excessive stimulus artifact or may even put the patient at risk foraccidental electrical shock. Care should also be exercised in the positioning ofwires connecting the stimulator to the stimulating electrodes. When possible,suspend these wires in the air, away from any other wires or metal objects. Itmay also help to separate the stimulating cable from the recording cable as it isled off the sterile field to the EMG machine.

Most modern recording instrumentation now employ isolation amplifiers toaugment stimulus isolation. The recorder portion of the EMG machine is opticallyisolated from ground by isolation amplifiers that reduce stimulus artifact evenmore, in addition to enhancing patient safety. Each recording channel will have apositive (+) and negative (−) active input and also an isolation ground connection.



This isolated ground connection is not a true ground and would not be con-nected to any other part of the EMG machine. It cannot become part of a so-called ground loop. Thus, when properly connected, the patient is not attachedto any true ground. The isolation ground connection on the EMG machine maysafely be attached to the patient and may help to reduce electrical interference.This connection is not essential, however, and we routinely conduct studieswith no ground connection at all.

The recording sensitivity should initially be set to approximately 100 µV/cmor 1 mV for full-screen deflection [5, 8, 14]. At this sensitivity one shouldclearly see stimulus artifact at the beginning of the trace. If not, it will be nec-essary to troubleshoot in an effort to detect the source of the problem. Trou-bleshooting will be discussed in a later section. When a trace has been obtainedthat shows some stimulus artifact, the intensity of stimulation can be increasedto a range of 6 to 8 V. If no nerve action potentials can be seen under these con-ditions, the recording sensitivity can be progressively increased to approxi-mately 20 µV/cm. At this sensitivity stimulus artifact should be quite large, andone may have to inspect the tail of the stimulus artifact closely to determine ifa CNAP is present. The stimulus artifact decays as an exponential curve, andthe shape of this curve is dramatically affected by the settings of filters [20].

The slope of the exponential decay of the stimulus artifact is most affectedby the low-frequency filter setting. We would normally begin recording with alow-frequency filter setting of about 10 Hz. At this setting the exponential decayis relatively slow and causes the tracing to be fairly flat. However, some ampli-fiers would saturate under these conditions, and the trace would appear flat ateither the uppermost or lowermost part of the display screen. If this happens,it will be necessary to increase the low-frequency filter setting to 30 or even100 Hz. Under these conditions, the slope of the stimulus artifact will be muchsteeper and the amplifier should emerge from saturation. However, this maymake the CNAP difficult to see.

The high-frequency filter setting that we routinely use is between 2500 and3000 Hz. This does not usually affect the shape of the CNAP, which has anequivalent frequency of approximately 500–2700 Hz. It will remove extraneoushigh-frequency noise from many other sources. The high-frequency filter set-ting will not affect the rate at which the amplifier emerges from saturation. Animportant point to remember in selecting filter settings is that the CNAP shouldnot be affected in an effort to reduce stimulus artifact or extraneous noise [20].

If an evoked potential machine is being used to record the CNAP, there maybe a 60 Hz notch filter available. This should not be used under any circum-stances, since it may produce an effect called “ringing.” With stimulation, adampened oscillation will become part of the stimulus artifact. This dampenedoscillation may look very much like a CNAP and confuse the observer. For thisreason, most EMG machines do not contain a 60 Hz notch filter. In any case, it



is not advisable to use a 60 Hz notch filter when stimulating and recordingfrom peripheral nerve.

4 ELECTRODES FOR INTRAOPERATIVERECORDING AND STIMULATION

More than 30 years ago, we developed our own electrodes for stimulating andrecording from nerve tissue. During the ensuing years we have been able torefine them, adding helpful features. Examples of these can be seen in Fig. 8.3,

FIGURE 8.3 Electrodes for stimulating and recording CNAPs can be made in many sizes, accord-ing to one’s needs. Illustrated here, from left to right, are miniature, midsize, and large electrodes.The stimulating electrode contains three contacts, and the recording electrode contains two. Theinset enlargement of the electrode tips illustrates the curved hooks on which exposed nerve can besuspended. The tip separation of the recording electrodes can be adjusted according to the size ofthe nerve from which recordings are made.



which demonstrates the simple and convenient design of these electrodes. Therequirements for electrodes include durability, reliability, and functionality.The electrodes should withstand steam autoclaving and the rigors of routinehandling together with other surgical instruments. They should have electri-cal characteristics that are conducive to safe stimulation and effective record-ing. The stimulating electrode contacts should never be made of silver.Although the resistance of silver wire is very low, stimulation through silverelectrodes deposits silver salts that are toxic to nerve. Any metals used fortissue contact should have good tissue compatibility. The electrodes shouldhave low electrical resistance, and they should resist tarnishing. They shouldalso have adequate strength to hold their shape even under the weight and pullof nerves suspended on them. We have found stainless steel electrodes to beeffective, and their cost is modest compared to that of noble metals such asplatinum [5, 8, 14].

The recording electrodes that we use consist of a handle that is made from ahigh-temperature plastic (acetal), which is easy to clean. Attached to the handleare two Teflon-insulated stainless steel electrodes approximately 8 cm long.For large-sized electrodes these are 1.125 mm in diameter, for medium-sizedelectrodes they are 0.875 mm in diameter, and for the miniature electrodes theyare 0.625 mm in diameter. The ends are blunted and bent like a shepherd’scrook and can be used to pick up and suspend the nerve. The tips of these elec-trodes are separated by a distance of 5 to 7 mm for the large-sized electrodes, 3to 5 mm for the medium-sized electrodes, and 2 to 3 mm for the miniature-sizedelectrodes. The distance between the tips of the recording electrodes deter-mines, in part, the amplitude of the CNAP. If the distance between the tips ofthe recording electrodes is too small, the size of the CNAP will be reduced andinappropriate amounts of amplification may be required to see the CNAP. Athigh amplification, then, stimulus artifact could become a problem. Thisemphasizes the need to maintain an adequate distance between electrode tips,which should always be greater than the length of active nerve during theCNAP. If both recording tips are applied to a section of nerve that is simulta-neously active, the size of the CNAP may be markedly reduced. The length ofactive nerve is considerably larger than one might imagine based on theanatomy of nodes of Ranvier. This is due to the fact that saltatory conductionin myelinated fibers is not simply regeneration of the action potential at suc-cessive nodes of Ranvier but rather a process in which several nodes of Ranvier(two to three) are activated simultaneously. One only needs to do simple arith-metic to show this. By considering the period of time required to produce anaction potential at a single node of Ranvier and also the distance between nodesof Ranvier, a theoretical conduction velocity can be calculated. This theoreticalconduction velocity is only one half to one third the observed conduction veloc-ity in myelinated fibers [15, 16]. This fact dictates that action potentials must



jump several nodes of Ranvier at a time, as is illustrated in Fig. 8.4. This processindicates that the length of active nerve is greater as a result of this phenome-non. Therefore, Fig. 8.4 illustrates that a consistent distance between the tipsof the electrodes must be maintained. One of the electrode tips must lie on thepart of the nerve that is not active, and the other must contact the active part ofthe nerve.

The electrodes are soldered to a 10-ft length of flexible, Teflon-insulatedwire that permits these wires to be led off of the sterile field. The Teflon insu-lation resists abrasion and is also unaffected by high-temperature autoclaving.Appropriate plugs are used on the ends of these wires to permit attachment tothe recording instrumentation. It should be noted that soldering to stainlesssteel requires special soldering flux and some skill. The stainless steel electrodesare then embedded into the acetal handles using methacrylate cement. Strain-relief is provided to the wires leaving the acetal handles to prevent bendingfatigue and eventual breakage of the wires.

Similarly, stimulating electrodes are also fabricated with stainless steel elec-trodes and an acetal handle. However, in this case, three electrodes are embed-ded into the handle. These electrodes are also blunted and bent like a shepherd’scrook to support the suspended nerve. Tip separation is similar to that for therecording electrodes. This tripolar electrode is used to circumvent a special sit-uation that exists when stimulating a nerve in continuity. As can be seen inFig. 8.5, stimulation with a bipolar electrode produces two current paths, oneshort and one quite long. The longer current path seen in this figure is veryundesirable because it leads to excessive stimulus artifact, especially when thedistance between stimulating and recording electrodes is very short. In addition,

FIGURE 8.4 Saltatory conduction in myelinated axons occurs as small groups of nodes of Ranvierbecome active simultaneously. This conduction increases the length of active nerve and requires agreater distance between the tips of the recording electrodes. Reprinted from [5].



it may permit the spread of stimulation over long lengths of the nerve whenhigher intensities of stimulation are used. The tripolar electrode that we havedeveloped breaks the longer current path and so reduces stimulus artifact andhelps localize stimulation. In the tripolar electrode, the outermost electrodes areconnected together so that there is no potential difference between them. Thereare still two current paths in this situation, but they are both short and local-ized to the region of contact with the nerve. There is very little spread of stim-ulation with the tripolar electrode [5].

The electrodes described here have been used successfully for many yearsand have proven their durability, reliability, and functionality. To maintainthese electrodes over many years, we recommend gas sterilization for routineuse, though they will withstand occasional high-temperature steam auto-claving. They can even be flash-sterilized should they become accidentallycontaminated during a surgical procedure. Steam autoclaving, however, hasa tendency to make plastics become brittle, and this eventually leads to adegradation of the electrodes. An occasional soaking in Instrument Milk (acleaning and lubricating solution frequently applied to surgical instruments)will retard this degradation. The electrodes can be cleaned routinely with hotsoap and water. In addition, their exposed metal tips will accumulate a pro-tein coat of coagulum, and this should be periodically removed. Soaking theelectrodes overnight in a solution of 30% bleach will soften and remove thiscoagulum.

FIGURE 8.5 Stimulation of nerve in continuity presents an unusual situation in which bipolarstimulation, top, produces two current paths. There is a very short path directly between electrodes,but there is also a second, longer path through the nerve and through the forearm. This second pathpasses beneath the recording electrode, producing large quantities of stimulus artifact. Tripolarstimulation, bottom, breaks the longer current path and localizes the stimulus to the region of elec-trode application. This dramatically reduces stimulus artifact, especially when the distance betweenrecording and stimulating electrodes is short. Modified from [5].



5 ANESTHETIC CONSIDERATIONS

There are few pharmacologic considerations in making operative peripheralnerve recordings. Inhalational agents and narcotics do not affect peripheralnerve function, and neuromuscular blocking agents may or may not be used,depending upon personal preference. The latter may prevent evoked musclecontractions, but this information is only useful in an ancillary way. Peripheralnerve surgery often involves surgery on a limb, and it is common to apply atourniquet to control bleeding. We do not use a tourniquet, but if one is used,it should be released at least 20 min prior to any neurophysiological studies. Ifthe tourniquet pressure is maintained, the nerve may not be functional and thefindings of CNAP studies may be misleading. Local anesthetics placed into orclose to the nerve can also block nerve conduction.

6 RECORDING CNAPs INTRAOPERATIVELY

Once the level of a lesion to peripheral nerve has been determined by physicalexamination, patient history, and preoperative neurophysiological studies, sur-gical exploration can be carried out. A length of nerve is exposed that shouldinclude the site of the lesion. Over the years, we have seen many examples oflesions that appear benign yet prove to be complete and offer no indication ofearly successful regeneration. Similarly, we have also seen examples of large neu-romas in continuity that encompass only one or two fascicles and spare adjacentfascicles or when the whole cross section is involved but it still conductsresponses. The visual appearance of a lesion in continuity may be deceptive. Wehave successfully recorded from lengths of nerve as short as 4 cm. With thisshort distance, stimulus artifact can become an overpowering consideration, andlonger lengths of nerve (8–10 cm) will facilitate recording. If a 4-cm length ofnerve is not accessible, it may be necessary to stimulate or record percutaneouslyat a distant site. This can be accomplished by using skin electrodes or subder-mal needle electrodes at some point down the length of the nerve. We begin byapplying stimulus pulses of 0.02 ms duration and 6 to 8 V intensity. This stim-ulus is usually applied proximally, and recording electrodes are placed distally.When stimulation is applied distally and recordings made proximally, the sizeof the compound nerve action potential may be slightly reduced by fibers thatare added to the nerve at proximal levels and are not subjected to the stimulat-ing electrodes. The active fibers may thus become “buried” by the fibers that arenot being stimulated and consequently do not produce action potentials. For thisreason, a proximal response to distal stimulation may be reduced in size.

To record potentials from the distal electrodes, the amplifiers are set at asensitivity of 200–500 µV/cm. A time window of 0.5–0.1 ms/cm is set. Underthese conditions normal nerve will produce a clear CNAP. If no response can



be seen, the sensitivity of the recorder will then be increased progressively downto 10 µV/cm. A small potential from regenerating nerve can be seen in Fig. 8.6.If there is still no clear CNAP, the stimulation will be increased progressivelyto levels of 50 V or more. If there is still no visible CNAP, this indicates theabsence of significant numbers of adequate fibers and dictates resection andrepair. For initial recordings, we do not use the signal-signal-averaging featurefound on many EMG machines to enhance recordings of CNAPs. This tech-nique is so sensitive that it may record very small numbers of fine fibers andindicate significant function in a segment of nerve that has no significant func-tion. Once we do see a CNAP on each single trace, we may then average anumber of traces to provide a clear, stable response for the patient’s record.

7 CRITERIA FOR APPRAISING A CNAP

If the CNAP is present, it will meet the following criteria. The putative responsewill be phase-locked to the stimulus, causing it to appear in a fixed position onthe recorder screen each time a stimulus is delivered. It will appear “frozen” onthe screen with repetitive stimulation, and its amplitude will always be less than2 mV. A response larger than 2 mV is more likely a muscle action potential. Inaddition to being larger, evoked muscle action potentials usually have a longerduration than the CNAP. Thus an evoked response with a duration greater than2 ms is likely to be a muscle response. Muscle responses also tend to be polypha-sic, whereas CNAPs are not. The response should exhibit threshold behavior asthe stimulus intensity is raised and lowered. It should also exhibit a maximumsize with increased stimulation. If visible contraction of adjacent muscle can beseen during stimulation, the stimulus intensity can be lowered until the musclecontraction stops and a small CNAP can still be seen. This may help distinguish

FIGURE 8.6 This small CNAP was recorded from a section of nerve undergoing appropriate regen-eration. The low amplitude and slow conduction velocity distinguish it from the CNAP of normalnerve. The presence of such a response is an indication for conservative treatment of a lesion.



a muscle action potential from a CNAP. The duration of the CNAP should beless than 2 ms. Most CNAPs are not polyphasic, though under some particularconditions they may be. This may occur when some fascicles in the nerve areundergoing regeneration while others are recovering from a neurapraxic injury.

It is helpful to begin stimulation and recordings on a segment of nerve thatis presumed to be normal. This may be a portion of the nerve proximal to a vis-ible point of injury or an adjacent nerve accessible within the operative site. Bystimulating and recording from a section of nerve that was functional preoper-atively, one can verify that the instrumentation is working properly and onecan be comfortable with an observation of no function in a section of adjacentnerve. A great advantage of the electrodes that we use is that they can slide alongthe length of nerve easily. In doing this, care must be taken to maintain goodcontact with the nerve. If these electrodes are held perpendicular to the floor,gravity becomes an ally, pressing the nerve against all of the contacts of the elec-trodes evenly. This ensures appropriate stimulating and recording conditions.With this technique, proximal recordings from normal nerve can be comparedto recordings made over and across a lesion in continuity and also distal to thelesion. Changes in the CNAP recorded at different levels of the nerve can thenbe related to the functional status of the nerve at those levels.

Often, there may be little anatomical indication of a lesion along the lengthof a nerve, and these operative recordings can localize the problem. Again, ifone recorded proximally and slides the distal stimulating electrode along thelength of the nerve, the recorded CNAP would be lost at the point where axonalcontinuity is lost. In our experience, resection of nerve at this point shows thatthe specimen removed contains mostly scar and few, if any, axons.

Intraoperative stimulation of peripheral nerve is often accompanied byevoked motor responses if the anesthetist has not blocked the neuromuscularjunction. Although this observation may lend support to observations ofperipheral nerve action potentials, it should not be used by itself as an indica-tion of good functional connection with muscle. For example, we have seenpatients with clear evoked motor activity who, preoperatively, had no voluntarycontrol over a particular muscle following a nerve injury of long standing. Withoperative nerve stimulation there may be clear contractions of the muscle inner-vated. Collectively, these findings indicate that, with extended time, smallaxons may regrow and reach their target muscles. However, the motor unitsthat they form are too small to mediate voluntary movements. When all of thesemotor units are synchronized by electrical stimulation of their nerve supply,they may produce a visible contraction even though such contractions cannotbe produced voluntarily. Thus the manifestation of a visible contraction ofappropriate muscles may not be an indication of adequate functional nerveregeneration. Even though stimulation of the nerve above the lesion will exhibitthis phenomenon, the lesion should still be properly resected and repaired if itdoes not transmit a recordable CNAP.



For very proximal root or spinal nerve injuries, it may become necessary tostimulate spinal nerves and record from nerve trunks. In the case of a root avul-sion, this preganglionic injury (between dorsal root ganglion and spinal cord) tothe sensory root will produce a relatively large and rapidly conducting CNAP.If, by contrast, regeneration is occurring, the CNAP will be smaller and will havea slower conduction velocity in the range of 20–40 m/s. If there is a combinationof postganglionic and preganglionic injury without effective regeneration, therecordings will be flat with no CNAP. For this type of extensive injury, the dis-ruption of the axon proximal and distal to the dorsal root ganglion usually killsthe cells of the dorsal root ganglion. For these cases we can section spinal nerveor roots proximally to prove the lack of proximal fascicular structure. We mayalso stimulate the exposed elements in the neck and record from the sensorycortex. In this regard, we have used somatosensory evoked potentials (SEPs) toget some indication of connection of nerve roots to the central nervous system.The complete absence of an SEP on stimulation of the nerve root indicates a com-plete avulsion and precludes surgical repair. The presence of an SEP upon nerveroot stimulation should be viewed with some caution, however, since previousstudies have shown that stimulation of even a very small number of fibers can pro-duce a normal SEP [22]. If an SEP can be recorded following root stimulation, itshould not be taken as evidence of normal function in the proximal parts of theroot. Thus an absent SEP provides more definitive information than one that ispresent. When there is no SEP, one can accurately assume that there is no prox-imal connection.

Such findings can often be verified by preoperative EMG studies conductedon peripheral parts of the nerve. In the case of an avulsive injury, the intact sen-sory axons produce a normal CNAP in the distal sensory branches. The elec-trical characteristics of the distal axon remain fairly normal with stimulation,and recording distal to the dorsal root ganglion will reveal the presence of thesesurviving axons. However, needle EMG studies will indicate profound dener-vation in all of the muscles supplied by this root. The distal motor axons willall have undergone Wallerian degeneration. The combination of normal sen-sory studies together with profound denervation of muscle indicates a veryproximal, avulsive injury. In addition, the complete absence of an SEP uponstimulation of these distal axons may also demonstrate a complete avulsion.

8 OPERATIVE RESULTS

Between 1965 and 1990 intraoperative recordings have been done in over 2000patients. We have recorded through lesions in continuity in the upper and lowerextremities of 877 patients, brachial plexus lesions in 432 patients, nerve tumorsin 245 patients, nerve entrapments in 617 patients, and cranial nerve palsies in62 patients. These numbers do not include patients with pelvic plexus involvement,



birth palsies, or injuries to smaller nerves such as digital, cutaneous antebrachii,sural, or saphenous nerves. In addition, this analysis does not reflect the factthat we often recorded from less involved or intact nerves in the neighborhoodof the more seriously injured nerve. These data are not included in the analy-sis, since CNAP recording was not used in those cases to determine partialinjury or regeneration. CNAP recording from these more intact nerves was doneeither out of scientific interest or to ensure that our instrument settings forrecording from the more seriously injured nerve were adequate.

Tables 8.1–8.5 show the results for upper- and lower-extremity nerves at dif-ferent levels. Although loss associated with these lesions in continuity was usually

TABLE 8.1 Criteria for Grading Whole Nerve Injury (LSUMC System)

0 (absent) No muscle contraction. Absent sensation

1 (poor) Proximal muscles contract but not against gravity Sensory grade 1 or 0.

2 (fair) Proximal muscles contract against gravity, distal muscles do not contract,sensory grade if applicable was usually 2 or lower.

3 (moderate) Proximal muscles contract against gravity and some resistance, some distal muscles contract against at least gravity, sensory grade was usually 3

4 (good) All proximal and some distal muscles contract against gravity and some resistance. Sensory grade was 3 or better

5 (excellent) All muscles contract against moderate resistance; sensory grade was 4 or better

TABLE 8.2 In Continuity Cases Studied (1965–1990) UpperExtremity Nerves

(+) NAP = (−) NAP =Neurolysis/Result∗ Repair/Result

MedianUpper arm 23/22 16/11•Elbow forearm 25/24 16/12•Wrist 24/24 17/14

72/70 49/37

RadialUpper arm 30/28 62/42+Elbow 10/9 8/7PIN 5/5 4/4Forearm 1/1 4/2SSR 3/3 6/6

49/46 84/61

121/117 (97%) 123/98 (79%)

∗Result = Those achieving a grade 3 or better result• = 1 split repair+ = 2 split repairs



complete both clinically and neurophysiologically before operation, there weresome exceptions. In the upper- and lower-extremity nerve lesions, some oper-ations were necessary for relief of severe pain or for partial but still severe func-tional loss distal to the lesion. Thus 70% of patients with median nerve lesionshaving complete functional loss distal to the lesion before operation had posi-tive intraoperative recordings. For radial nerve lesions this figure was close to74%, and for ulnar nerve lesions it was 68%. For lower-extremity nerves, pre-operative functional loss was complete in 65% of patients. Although the major-ity of lower-extremity nerve lesions had complete functional loss in theirdistributions at the time of operation, there were important exceptions. Theseincluded injection injuries with incomplete loss but severe pain, gunshotwounds associated with partial loss and sustained pain, and a variety of otherincomplete injuries affecting femoral or the more distal tibial nerve. Brachialplexus lesions are listed as having complete or incomplete functional loss at thetime of their evaluation (see Table 8.4). They are also tabulated as major ele-ments involved and evaluated, as well as cases operated on.

Patients with tumors involving nerves usually had little or no functional losspreoperatively. Intraoperative CNAP recording was used to test fascicles enter-ing and leaving intraneural tumors and to check progress of the dissection inother cases. For example, in 68% of 69 solitary neurofibromas involving nerves,major function in the innervating field of the particular nerve could be pre-served despite total tumor removal by using intraoperative recordings and fas-cicular dissection.

As can be seen in Tables 8.2–8.5, when a lesion was partial to begin withor, more frequently, had complete functional loss and yet a recordable CNAP,neurolysis alone led to an eventual recovery. Thus 93% of nerves having a

TABLE 8.3 In Continuity Cases Studied (1965–1990) Upper Extremity Nerves

(+) NAP = (−) NAP =Neurolysis/Result∗ Repair/Result

UlnarUpper arm 17/16 16/7•Elbow forearm 45/43 14/10•Wrist 8/8 8/5+

Combined median-ulnar 40/36 48/30

Combined median-radial 11/8 5/4

Combined median-ulnar- 4/4 8/6radial

125/118 (93%) 99/62 (61%)

∗Result = Those achieving a grade 3 or better result• = 1 split repair+ = 2 split repairs



recordable CNAP that underwent subsequent neurolysis recovered to a grade3 or better (see Table 8.1 for grading method). From another perspective,82% of patients had a grade 4 or 5 recovery, which represents a very accept-able outcome.

Of equal importance is the fact that when CNAPs were absent and a lesionin continuity was resected, pathological studies confirmed that the lesion wasalways neurotmetic or a Sunderland grade 4 nerve lesion. Such lesions had littleor no potential for spontaneous regeneration that might lead to useful function.

Optimal timing for recording varies according to the mechanism of injury.In lengthier lesions like those produced by stretch and/or severe contusion,

TABLE 8.4 In Continuity Cases Studied (1965–1990) Lower Extremity Nerves

(+) NAP = (−) NAP =Neurolysis/Result Repair/Result

Sciatic Tibial Peroneal Tibial PeronealButtock 30/28 28/23 23/20• 19/6•Thigh 38/36 34/31 37/33+ 43/19•

Tibial 13/12 11/10•Peroneal 34/30 69/15+Femoral 15/13 14/7

193/175 (90%) 216/110 (51%)

• = 1 split repair+ = 2 split repairs

TABLE 8.5 Brachial Plexus In Continuity Elements Studied (1965–1990)

(+) NAP = (−) NAP =Neurolysis/Result Repair/Result

Injury Mechanism Complete Incomplete Complete Incomplete

Lacer. in contin. 10/9 18/17 15/10 4/3(12)

GSW’s (90) 41/40 47/44 116/64∗ 8/7•Iatrogenic (30) 18/17 17/17 32/23• 6/4

Stretch/Contusion 93/84 102/96 336/150• 45/28+(300)

162/150 184/74 499/247 63/42

• = 1 split repair Complete = Complete loss in distribution of one or+ = 2 split repairs more major elements preoperatively∗ = 5 split repairs Incomplete = Incomplete loss of function felt to be in

the distribution of element testedCases are listed in ()



it takes longer for significant regeneration than can be recorded by direct CNAPstudies. Thus most fracture-associated contusions and gunshot wounds can betested operatively at 2 to 3 months post injury, whereas plexus stretch injuriesare more reliably evaluated at 4 or 5 months after injury. On the other hand,recording can be done as an adjunct to tumor resection at any time and can beused as an investigative tool for entrapment or compressive neuropathies atany point in the course of these disorders.

Intraoperative recording has been helpful in a relatively large number ofpatients with palsy of the accessory nerve. Loss of function in these patients wasusually iatrogenic and due to lymph node biopsy or removal of a neck lesionand inadvertent damage to nerve distal to its innervation of sternocleidomas-toid muscle. When the lesion was in continuity, as it was in 26% of cases, oper-ative CNAP studies were done. This approach led to resection of about 50% ofsuch accessory nerve lesions in continuity. These proved to be neurotmetic orSunderland grade 4 nerve lesions. The other accessory nerve lesions in continu-ity had a neurolysis with a good outcome (average postoperative grade was 3.9).

Although not essential for operative management of entrapment neuropathy,CNAP recordings were usually done and had interesting features. A directrecording was first made proximal to the presumed entrapment site. The actualentrapment site was then defined by progressively moving the recording elec-trodes in a distal direction toward, into, and across the presumed entrapmentsite. Mild degrees of decreased conduction velocities were sometimes seen wellproximal to an area of more severe conduction problems. Only in a few casesdid this appear to be due to separate lesions or what has been described as a“double crush syndrome.” On the other hand, operative conduction across thearea of entrapment was almost always more severely affected than might havebeen predicted by the preoperative EMG studies. This may relate to the fact thatthe distance between the stimulating and recording sites was less at the time ofintraoperative recordings than at the time of EMG studies. These differenceswere usually most obvious in patients with ulnar entrapments at the elbow andthose with presumed entrapment of the peroneal nerve over the region of thehead of the fibula.

In only five examples of true distal cubital tunnel syndrome did ulnar nerveentrapment appear clinically or neurophysiologically at the level of the twoheads of flexor carpi ulnaris and distal to the olecranon notch. On the otherhand, slowing of conduction velocity with ulnar nerve entrapment at the elbowusually appeared to be maximal either just proximal to the olecranon notch or,more often, within the level of the olecranon notch itself. Thus 341 of the350 patients studied for ulnar nerve entrapment at the level of the elbow hadneurophysiological findings indicating maximal lesioning just proximal to orin the notch. Also of interest were intraoperative recordings on patients withposterior interosseus nerve entrapments. The area of maximal abnormality in



conduction, while usually beginning at the arcade of Frohse, appeared toextend beyond that level distally and beneath the actual volar head of the supina-tor itself.

Some unusual entrapments or functional lesions to nerve have been furtherdocumented by intraoperative recording (see also Table 8.6). These haveincluded radial nerve lesions at the level of the long head of the triceps, medianas well as ulnar nerve entrapments by Struthers’ ligament, and irritative as wellas compressive sciatic lesions just below the buttocks crease due to hamstringhypertrophy. There were many more lesions of plexus spinal nerves where tho-racic outlet syndrome was suspected and intraoperative recordings showed con-ductive defects. These areas of reduced conduction velocity were more dramaticon the lower roots (especially C8 and T1) but at times were seen at C7 as well.Conductive defects in these patients began at a spinal nerve or spinal nerve totrunk level but not more distally. By comparison, conduction velocities andamplitudes recorded from C5, C6, and usually C7 roots were almost alwaysgreater than those in lower roots in the patients with “true” thoracic outlet syn-drome. In these cases there was often some weakness of hand intrinsic musclesin both the median and ulnar nerve distributions.

9 TROUBLESHOOTING

The operating room is generally regarded as a hostile setting for neurophysio-logical recording using electronic instrumentation. It is likely that those start-ing a program of intraoperative neurophysiology will encounter someproblems, at least initially, and have to perform the task of troubleshooting.Troubleshooting involves observation of existing conditions which may beproblematic and knowing how to effectively deal with them. The powers ofobservation cannot be overemphasized. The sources of problems vary widely,though they can be put into several general categories. They may come in theform of the spontaneous and continuous electrical noise, which preventsrecordings, or, more commonly, in the form of an inability to stimulate andrecord from sections of nerve that are known to be normal. This section isintended to provide a basis for dealing with these problems.

TABLE 8.6 Other In Continuity Cases Studied (1965–1990)

Intraneural Tumors of Brachial Plexus 80

Intraneural Tumors of Other Nerves 165

Entrapments 617

Cranial Nerve Injuries 62 (VII,XI,XII)



With electrodes applied to the nerve and the instrumentation adjusted to thesettings described previously, one should view the display of the recordingequipment. With the intensity of the stimulator turned all the way down, thetrace should be relatively flat. If not, and the trace displays large regular andcontinuous excursions, there may be several sources for the interfering signal.The most common of these is 60 Hz interference from electrical powersources. This can be readily identified by temporarily increasing the display to10 or 20 ms per division. The most offensive devices would be those that con-tain electric motors. Hospital beds, pumps, and hot-air or fluid warmers aregood examples. Turning these devices off may not prevent the interference,however, and they may have to be unplugged. Although older forms of fluo-rescent lighting were a significant problem in the past, modern fluorescentlighting rarely presents a problem. Sometimes, however, x-ray view boxes canproduce an artifact, and these should be turned off when the problem is iden-tified. Methodically unplugging, briefly, each of the devices identified as a pos-sible source of the problem may help to eliminate the source of noise. If thesource of the noise cannot be found, the electrodes should be disconnectedfrom the EMG machine while the EMG machine is still recording. If the noiseremains, it is most likely originating from the instrumentation itself, arrivingthere through electrical power lines. It may be necessary to plug the EMGmachine into a different outlet. More commonly, however, the interference willdisappear when the recording electrodes are unplugged, indicating that itssource is from the recording electrodes. One should inspect the routing of thewires from the recording electrodes as they are passed off of the sterile field. Ifthese wires are placed close to the power cords of other equipment, they maybe the source of the interference. These wires should preferably be suspendedin air from the operating table to the recording input; they should not be placedadjacent to any other metallic objects. In addition, these wires should not move,either from evoked muscle activity in the patient or simply from air currentsaround them. Movement, by itself, will produce electrical interference.

Current protocols specified by the Joint Commission for the Accreditationof Hospitals ( JCAH) require that patients on the operating table must not beconnected to any true ground. Thus the reference for the electrosurgical unit(Bovie) and any other electrical equipment connected to the patient should notbe grounded. The operating table itself is not grounded. Attaching the isolatedground from the EMG machine to the patient may help to eliminate the sourceof noise under these circumstances. This may be done using a large-surface-areadisposable ground pad attached to the patient’s body at a point that is as closeto the recording site as is convenient.

With the recording electrodes attached to the EMG machine, the surgeonshould be able to make contact between tissue and both recording electrodes, asthe trace of the recorder remains flat. If there is a great deal of difference in the



amount of noise displayed on the recorder as the surgeon touches both record-ing electrodes to the patient, there may be a broken or bad connection betweenthe EMG machine and the recording electrodes. If only one of these electrodesactually makes connection with the patient, it will lead to excessive amounts ofnoise. This may occur if one of the wires to the electrodes is broken or if thereis poor contact between a wire and the plug attached to it. Bad electrical contactbetween the nerve and the electrodes will lead to a similar result and may occurif the electrodes have not been properly cleaned. It may be helpful to scrape thestainless steel surface of the electrodes that contact the nerve. This will producea low-resistance junction that facilitates stimulation and recording.

Other sources of spontaneous, continuous interference include radio trans-mitting devices (telemetry), electrosurgical units, and spontaneous EMG. Thesesources of interference are high frequency and tend to fill the screen of therecorder. They may or may not be regular in appearance. In this case, it may benecessary to use the filters on the EMG machine to attenuate the noise, as wasdiscussed previously. Occasionally, some unusual sources of interfering noisecan be identified, including implanted stimulators and pacemakers.

Another challenge to monitoring is artifact related to the stimulus. Excessivestimulus artifact can be caused by a loss of stimulus isolation (which has alreadybeen discussed) or by improper filter settings. Insufficient distance betweenstimulating and recording electrodes or insufficient distance between recordingelectrode tips may also lead to excessive stimulus artifact. A lack of adequateseparation between stimulating and recording cables as they lead off the sterilefield may capacitively produce excessive stimulus artifact. High-intensity stim-ulation or using long-duration stimulus pulses may also contribute to stimulusartifact problems. Although all recordings should contain some degree of stim-ulus artifact, it should not be so great as to prevent visualization of the CNAPimmediately following it. In fact, if no stimulus artifact can be seen, it may bean indication of insufficient amplification or a failure of stimulation. As onebecomes familiar with this technique, the appearance of a modest amount ofstimulus artifact is comforting.

Another feature of recordings that one quickly adjusts to is the sweep speedof the recording instrument. This should be adjusted to approximately 1 ms/cmor a total sweep length of approximately 10 ms. If the display is set for too longa window of time, the CNAP will be lost in the stimulus artifact at the verybeginning of the trace. Those accustomed to viewing SEPs will quickly appre-ciate that the CNAP has a much shorter latency and is a much faster event. Thesweep required to view this event must be considerably faster than that requiredfor the SEP.

In an effort to expedite troubleshooting, a flowchart is presented in Table 8.7.Following the steps of this flowchart in a methodical way should permit one toidentify problems quickly.


Select Nerve level (min. 4 cm. Length)

Set Stim = 6-8 V Set Rec. = 100 mV/cm

Suspend Nerve on Electrodes

Can stimulus artifact be seen at the beginning of the trace?

Check electrode connectionsCheck stim. & Rec. settingsPossible recorder malfunction

NO

YES

YES

NO

NO YESEVALUATION:

Check:Appropriate nerve length?Good electrode contact with nerve?Separate Stim. & Rec. leads from electrodes?Shorten stimulus duration Check filter settings

Potential may beartifact or electricalnoise

NO “Response” always appears with exactly the same latency (appears “frozen” on screen)

YES

YES

NO

NO

NO

NO

NO

Amplitude at maximum less than 2 mV

YES

YES

YES

YES

Does potential show threshold behavior asstimulus is increased and decreased?

Is there too much stimulus artifact?

Does potential show maximum size withincreased stimulation?

Can potential be seen without muscle activity near the recording electrodes?

Waveform of CNAP is less than 2 mSecduration and not polyphasic?

Nerve activity indicates significant fiberspresent at this levelEVALUATION COMPLETEPROCEED TO ANOTHER LEVEL

Potential may bemuscle activity

Potential may bestimulus artifact

Potential may be artifact orstimulus may be spreading

Potential may be muscleaction potential

Potential could be muscleaction potential

Set Stim. = 25-35 VSet Rec. = 20 mV/cm

Go toEVALUATION

YES

NO

Test System: Check a segment ofnerve which is known to be functional

NO YES

Check:Are electrode connections good?Is stimulator working touch exposedmuscle; does it contract?Is recorder working some stimulus artifactat beginning of trace?

Set Stim. = 70 VSet Rec. = 10 mV/cm

Previous segmentshows no nerve fiber activity?

Retest previoussegment

NO

YES

Go to EVALUATION

No Significant AxonsPresent!!TESTINGCOMPLETE

CNAP?

CNAP?

CNAP?

CNAP?

START

193

TABLE 8.7



10 CONCLUSIONS

Intraoperative neurophysiology is a new and exciting field that provides func-tional information to the surgical team. Despite the development of sophis-ticated new imaging techniques, these cannot provide the same kind ofinformation that neurophysiological studies can. With respect to peripheralnerve, intraoperative neurophysiology provides diagnostic as well as prognos-tic information that cannot be learned in any other way. Preoperative EMGstudies are very useful in evaluating the extent of a nerve injury, but even thesecannot detect the electrical manifestations of very early regeneration. This canonly be learned at the operating table. With this information in hand, the sur-geon can decide on the proper course of action to treat the nerve injury. Theassurance provided by these recordings gives him or her the proper feedbackthat his or her decisions are correct. The end result is that the patient willreceive the benefits of surgery that will produce the best prospect for optimalrecovery.

As with any new procedure, there will be apprehensions with implementa-tion. The novelty of a new technology in the operating room requires someadjustments and accommodation on the part of the surgical team. However,operative recording of peripheral nerve activity provides useful informationconcerning nerve function at the time of surgery, and the results are certainlyworth the small amount of extra effort required to obtain them. These record-ings can be made quickly and reliably and represent an effective means ofassessing the status of a segment of peripheral nerve. They provide assuranceto the surgeon that the difficult decisions that must be made to deal with alesion in continuity are based on good information and are not simply guidedby intuition.

REFERENCES

1. Kline, D.G., and Happel, L.T. (1993). Penfield Lecture. A quarter century’s experience withintraoperative nerve action potential recording. Can. J. Neurol. Sci., 20(1), 3–10.

2. Arai, M., Goto, T., Seichi, A., Miura, T., and Nakamura, K. (2000). Comparison of spinal cordevoked potentials and peripheral nerve evoked potentials by electric stimulation of the spinalcord under acute spinal cord compression in cats. Spinal Cord, 38(7), 403–408.

3. Carter, G.T., Robinson, L.R., Chang, V.H., and Kraft, G.H. (2000). Electrodiagnostic evalua-tion of traumatic nerve injuries. Hand. Clin., 16(1), 1–12, vii.

4. Grant, G.A., Goodkin, R., and Kliot, M. (1999). Evaluation and surgical management ofperipheral nerve problems. Neurosurgery, 44(4), 825–839; discussion 839–840.

5. Happel, L.T., and Kline, D.G. (1991). Nerve lesions in continuity. In “Operative nerve repairand reconstruction” (R.H. Gelberman, ed.), 1st ed, vol. 1, pp. 601–616. J.B. Lippincott,Philadelphia.

6. Kline, D.G. (1990). Surgical repair of peripheral nerve injury. Muscle Nerve, 13(9), 843–852.



7. Spinner, R.J., and Kline, D.G. (2000). Surgery for peripheral nerve and brachial plexus injuriesor other nerve lesions. Muscle Nerve, 23(5), 680–695.

8. Kline, D.G., and Hudson, A.R. (1995). “Nerve injuries,”1st ed. W.B. Saunders, Philadelphia.9. Williams, H.B., and Terzis, J.K. (1976). Single fascicular recordings: An intraoperative diag-

nostic tool for the management of peripheral nerve injuries. Plastic and Reconstructive Surgery,57, 562–569.

10. Oberle, J.W., Antoniadis, G., Rath, S.A., and Richter, H.P. (1997). Value of nerve action poten-tials in the surgical management of traumatic nerve lesions. Neurosurgery, 41(6), 1337–1342;discussion 1342–1344.

11. Chaudhry, V., and Cornblath, D.R. (1992). Wallerian degeneration in human nerves: Serialelectrophysiological studies. Muscle Nerve, 15(6), 687–693.

12. Lundborg, G., and Danielson, N. (1991). Injury, degeneration, and regeneration, In “Opera-tive nerve repair and reconstruction” (R.H. Gelberman, ed.), 1st ed., vol. 1, pp. 109–132. J.B.Lippincott, Philadelphia.

13. Lundborg, G., and Dahlin, L. (1991). Structure and function of peripheral nerve. In “Operativenerve repair and reconstruction” (R.H. Gelberman, ed.), 1st ed., vol. 1, 3–18. J.B. Lippincott,Philadelphia.

14. Kline, D.G., Kim, D., Midha, R., Harsh, C., and Tiel, R. (1998). Management and results of sci-atic nerve injuries: A 24-year experience. J. Neurosurg., 89(1), 13–23.

15. Dorfman, L., and Cummins, K.L. (1981). “Conduction velocity distributions: A populationapproach to electrophysiology of nerve.” W.R. Liss, New York.

16. Galbraith, J.A., and Myers, R.R. (1991). Impulse conduction. In “Operative nerve repair andreconstruction” (R.H. Gelberman, ed.), vol. 1, pp. 19–45. J.B. Lippincott, Philadelphia.

17. Mogyoros, I., Kiernan, M.C., and Burke, D. (1997). Strength-duration properties of sensoryand motor axons in carpal tunnel syndrome. Muscle Nerve, 20(4), 508–510.

18. Wall, E.J., Massie, J.B., Kwan, M.K., Rydevik, B.L., Myers, R.R., and Garfin, S.R. (1992). Exper-imental stretch neuropathy: Changes in nerve conduction under tension. J. Bone Joint Surg. Br.,74(1), 126–129.

19. Rochkind, S., and Alon, M. (2000). Microsurgical management of old injuries of the periph-eral nerve and brachial plexus. J. Reconstr. Microsurg., 16(7), 541–546.

20. Tiel, R.L., Happel, L.T. Jr., and Kline, D.G. (1996). Nerve action potential recording methodand equipment. Neurosurgery, 39(1), 103–108; discussion 108–109.

21. Holland, N.R., Lukaczyk, T.A., Riley, L.H. III, and Kostuik, J.P. (1998). Higher electrical stim-ulus intensities are required to activate chronically compressed nerve roots. Implications forintraoperative electromyographic pedicle screw testing. Spine, 23(2), 224–227.

22. Zhao, S., Kim, D., and Kline, D. (1993). Somatosensory evoked potentials induced by stimu-lating a variable number of nerve fibers in the rat. Muscle Nerve, 16, 1220–1227.


C H A P T E R 9

IntraoperativeNeurophysiologicalMonitoring of the SacralNervous SystemDAVID B. VODUSEK

University Institute of Clinical Neurophysiology, University Medical Centre, Ljubljana, Slovenia

VEDRAN DELETIS


1 Introduction2 Functional Anatomy

2.1 Neural Control of the Lower Urinary Tract2.2 Anorectum2.3 Sexual Organs

3 Clinical Neurophysiological Tests in Diagnostics4 Intraoperative Clinical Neurophysiology

4.1 Basic Technical Aspects of Stimulation for Intraoperative Sacral Monitoring

4.2 Basic Technical Aspects of Recording for Intraoperative Sacral Monitoring

4.3 Specific Sacral Neuromuscular System Monitoring Procedures

5 Discussion and ConclusionsReferences

ABSTRACT

In the first part of this chapter, the basic functional neuroanatomy of the genitouri-nary and anorectal systems is briefly described. These systems are involved in the so-called sacral functions (micturition, defecation, erection, ejaculation, etc.). In thissection we describe clinical neurophysiological tests of the functional integrity of the



198 David B. Vodusek and Vedran Deletis

sacral neuromuscular system used for diagnostic purposes. The second part of thischapter deals with intraoperative neurophysiological monitoring of the lumbosacralnervous system. The validity of different intraoperative monitoring techniques of thissystem is summarized.

1 INTRODUCTION

The functions involving the genitourinary and anorectal systems are uniquelycontrolled by the complex interaction of the vegetative and the somatic nervoussystem. Insofar as it is the sacral parasympathetic and somatic systems that con-stitute the most important peripheral nervous structures controlling these func-tions, they may also be referred to as sacral functions. The functions themselves(micturition, defecation, erection, etc.) are now better understood because wehave applied methods of measuring the different functional parameters (uro-dynamics, faecodynamics, measurements of the sexual response) that providefor better diagnosis of dysfunction. The awareness that such dysfunction is alsoa consequence of damage to neural structures has also greatly increased. On theother hand, it has become possible to better define the various lesions to thenervous system by electrophysiological methods. However, these methods byand large document only the somatic sacral nervous system and its centralpathways [1]. Nevertheless, such information is clinically relevant because (1)the somatic nervous system plays a part in all sacral functions, and (2) thesomatic and parasympathetic sacral systems are closely related, and informationon the somatic system may therefore be a relevant indicator of the overall neu-rogenic lesion in several clinical situations.

In fact, the common denominator of lower urinary tract, anorectal, andsexual functions is that many of their efferent and afferent pathways travel atleast partly in close vicinity. They “share” common spinal cord regulatory seg-ments (the upper lumbar segments—sympathetic efferents; the middle andlower sacral segments—parasympathetic and somatic efferents). Even the longpathways connecting the relevant spinal cord segments with higher levels of thecentral nervous system are situated close together. Thus it is not uncommonthat in lesions to the nervous system, and particularly in lesions affecting thespinal cord, cauda equina, sacral plexus, and pudendal nerve, the sacral func-tions are affected together. Dysfunctions may arise not only from disease ortrauma, but also from inadvertent lesions to the previously named structuresduring invasive procedures, particularly several surgeries involving the pelvicorgans and the spinal canal. The consequences of lesions to the neurocontrolof sacral functions include disturbing sensory phenomena like pain, dysethe-siae, urgency and frequency, loss of genital sensation, bladder or rectal fullness,and subsequent retention, obstipation, soiling, incontinence, and erectile dys-function. Neurogenic damage may lead to lost coordination between detrusor


Intraoperative Neurophysiological Monitoring of the Sacral Nervous System 199

and sphincter function, leading to high bladder pressures and upper urinarytract dysfunction. Incontinence may—particularly in motor-disabled persons—lead to problems with hygiene, skin problems, infections, and decubiti.Although neurogenic sexual dysfunction may not be life-threatening, it can beextremely disruptive psychologically and can lead to severe emotional andinterpersonal problems. All these may be particularly tragic when they are aconsequence of an inadvertent intraoperative lesion.

A whole array of clinical neurophysiological diagnostic methods has beenmodified for use in the anogenital area, including electromyographic methodsand reflex, conduction, and evoked potential studies [2,3]. These methods areroutinely employed in uroneurological and neuro-urological laboratories fordiagnostics and follow-up in patients with (suspected) neurogenic sacral dys-function. The authors have pioneered with trials to establish some of these neu-rophysiological methods in the operating room, to help the surgeon identifyparticular sacral nervous structures, and to monitor the function of the sacralneuromuscular system during surgery [4–7].

2 FUNCTIONAL ANATOMY

Although the functional anatomy of the genitourinary and anogenital systemsis highly complex, it need not be considered in detail because only the grossanatomy of the relevant somatic nervous structures can be approached by clin-ical neurophysiological methods that are applicable in the operating room envi-ronment. Most of the information relevant for intraoperative neurophysiologycan be summarized as follows.

Afferent fibers from the mucosa and skin of the genitoperineal region travelmostly with the pudendal nerves. The distally most accessible group of sensoryfibers are the dorsal nerves of the penis (or clitoris). The sensory fibers from thegenital, perineal, and anal region enter through the dorsal spinal roots S2–S5into the spinal cord and synapse (through interneurons) with sphincteric motorneurons. The afferent information also ascends (the primary sensory neuronssynapsing to higher-order sensory neurons at various levels) via the spinothal-amic and dorsal column tracts, the lemniscal system and thalamocortical tracts,and finally to the somatosensory cortex (at its interhemispheric location) [8].

The sphincteric lower motor neurons in the midventral spinal grey matter ofthe second to fourth sacral spinal cord segments (the “Onuf nucleus”) are undervoluntary control from the motor cortex. Somatic motor nerve fibers leavethrough the ventral roots and the sacral plexus, combining into the pudendalnerves; direct branches innervate the levator ani and the anal sphincter [8]. Theexternal urethral sphincter may be innervated by sacral somatic fibers travelingvia splanchnic nerves [9] or the pudendal nerve [10], or possibly both.



2.1 NEURAL CONTROL OF THE LOWER

URINARY TRACT

The lower urinary tract (LUT) is innervated by three sets of peripheral nerves.The pelvic parasympathetic nerves arise at the sacral level of the spinal cord(they excite the bladder and relax the urethra). The sympathetic nerves arisefrom the upper lumbar segments and inhibit the bladder body, modulate trans-mission in bladder parasympathetic ganglia, and excite the bladder base andurethra. The somatic efferents and afferents from the S2–S4 sacral roots inner-vate pelvic floor muscles (levator ani) both through direct branches and by thepudendal nerve, which innervates also the perineal muscles, including the analand urethral sphincter.

All of these nerves contain both efferent and afferent nerve fibers that arecontrolled by centers in the brain and particularly important centers in thebrainstem. Long tracts in the spinal cord subserve the spinobulbospinal reflexpathway, which is relevant for coordinated detrusor-sphincter function andnormal micturition. The dorsal pontine tegmentum is established as an essen-tial control center for micturition (with a close anatomical relationship with thelocus coeruleus). While different types of sensation of the lower urinary tracttravel both in the anterolateral and the dorsal part of the spinal cord, thedescending (motor) pathways lie within the lateral aspects of the spinal cord.

2.2 ANORECTUM

Touch, pin-pricks, and hot and cold stimuli can be perceived in the anal canalto a level of up to 15 mm above the anal valves. The epithelium in the area fromabout 10–15 mm above the valves has a rich sensory nerve supply made up ofboth free and organized nerve endings. The sensory endings in the hairy peri-anal skin are similar to those in hairy skin elsewhere. The afferent nerve path-way for anal canal sensation is by the inferior hemorrhoidal branches of thepudendal nerve. Sensory pathways from the rectum and the bladder travel inthe pelvic visceral nerves to the sacral cord, but some afferent information isprobably also related to hypogastric nerves entering the spinal cord at the tho-racolumbar level.

Functionally, the most important part of the smooth musculature of theanorectum is the internal anal sphincter, which is responsible for about 85% ofthe resting pressure in the lumen of the canal. The smooth musculature of rectalwalls (and of the detrusor) receives extrinsic motor innervation from the sacralparasympathetic outflow arising in the intermediolateral cell columns of sacralcord segments S2–S4. These first-order neurons send axons that emerge with



the ventral spinal nerve roots to synapse with second-order neurons lyingwithin the pelvic plexus or the visceral walls. The sympathetic nerve supplyarises from the thoracolumbar chain and travels in the hypogastric nerve toinnervate visceral smooth muscle directly, and also via a modulatory influenceon parasympathetic function at the level of the pelvic plexus. The internal analsphincter is probably controlled both by sympathetic (hypogastric) and sacralparasympathetic pathways, but the inhibition brought about by rectal disten-tion (the important rectoanal inhibitory reflex) is predominantly an intramuralone.

The external anal sphincter is innervated by the pudendal nerve andoccasionally also by a perineal branch of S4. The neurons of the sphinctermotor nucleus (Onuf’s nucleus) are under voluntary control via corticospinalpathways.

Normal defecation is probably triggered by filling of the rectum from the sig-moid colon, and the signals from stretch receptors in the rectal wall and pelvicfloor muscles are interpreted at the conscious level as a desire to defecate. Theextension of the rectum causes reflex relaxation of the smooth internal sphinc-ter muscle. Voluntary relaxation of the striated sphincter muscle permits defe-cation, which is assisted by colonic pressure waves and abdominal straining. Ifdefecation is to be deferred, brief conscious contraction of the voluntary sphinc-ter allows time for recovery of internal sphincter tone and relaxation of therectum to accommodate filling. Conscious appreciation of the desire to defecateand intentional control over defecation are conferred by suprasacral neuralinfluences. The precise way in which the autonomic, pyramidal, extrapyrami-dal, and sensory pathways integrate to achieve a reliable and predictable anorec-tal function is not yet fully understood [11].

2.3 SEXUAL ORGANS

Of the sexual functions affected by neurogenic lesions, research has centered onthe male functions, and particularly on erection. Erection can be initiated in thebrain and/or follow genital stimulation; in sexual activity a combination of bothis probably involved.

Neurogenic erectile dysfunction due to peripheral lesions can be secondaryto the disruption of sensory nerves contributing to the afferent arm of reflexerection or to the disruption of autonomic nerves that mediate arterial dilata-tion and trabecular smooth muscle relaxation. Erectile dysfunction can occurfrom disruption of the relevant pathways in centers within the spinal cord (bothsuprasacral and sacral), cauda equina, the sacral plexus, the pelvic plexus, thecavernosal nerves, and the pudendal nerves. Particular pelvic surgeries such asradical prostatectomy or cystoprostatectomy lead to a high percentage of



mostly neurogenic erectile dysfunction; the lesion occurs in the pelvic plexusor in the cavernosal nerves located in the posterolateral aspect of the prostate.

Ejaculation can be abolished by a lesion to the sympathetic innervation ofthe bladder neck (leading to a retrograde ejaculation) and by disruption of thesensory and (particularly) motor nerves innervating the perineal muscles,whose contraction leads to expulsion of the semen. It can also be abolished bycentral lesions.

A disturbed sexual response in females is due to (1) afferent lesions leadingto loss of sensitivity of the perineal area, and (2) efferent lesions leading to a lossof lubrication, loss of clitoral erection, and pelvic floor muscle denervation.

3 CLINICAL NEUROPHYSIOLOGICAL TESTSIN DIAGNOSTICS

Since the function of all the aforementioned systems relies on neural control,clinical neurophysiological tests have been introduced to support and supple-ment clinical evaluation in patients. The tests comprise electrophysiologicmethods of testing conduction through motor and sensory pathways (bothperipheral and central) and electromyographic methods. Traditionally, in test-ing both the lower urinary tract and anorectal function, the EMG signalobtained from sphincter muscles has been used to delineate the sphincter activ-ity patterns in relationship to micturition or defecation. In addition to that,electromyographic methods have been used to distinguish between normal andneuropathic pelvic floor muscles. Conduction tests have been introduced toevaluate the integrity of different reflex pathways (sacral reflexes), the individ-ual motor pathways (pudendal nerve terminal latency, MEP), and sensory path-ways (penile sensory neurography, SEP). In addition, autonomic tests have alsobeen introduced (sympathetic skin response, corpus cavernosum EMG). Fordiagnostic purposes a single testing is performed without knowledge of the pre-vious status of the investigated structure. In this diagnostic situation, resultshave to be compared to values obtained from healthy subjects. The tests of con-duction have been found to be relatively insensitive to axonal lesions becauseamplitudes of responses vary widely in the control population (particularly dueto technical reasons), and conduction may remain normal in partial lesions.Thus, in the diagnostic situation, the ability of the concentric needle EMG todetect abnormal spontaneous activity as an indicator of denervation, andchanges of motor unit potentials as indications of reinnervation, has been foundto be particularly helpful. EMGs and recordings of the bulbocavernosus reflex(indicating the potency of the lower sacral reflex arc) have been proposed as thebasic battery of tests for evaluation of patients with sacral dysfunctions and sus-pected neurogenic involvement [12]. From conduction tests, only recordings



of the sacral reflex and SEP after dorsal penile or clitoral nerve stimulation havebeen suggested since they have been validated by extensive clinical studies.They may be of value in selected patients with suspected peripheral (i.e., bul-bocavernosus reflex testing) and central nervous system (i.e., SEP testing)lesions [3, 13]. The other neurophysiological tests have been suggested asuseful in further research. The corpus cavernosum EMG is the most contro-versial of the tests so far described. It is not yet well clarified whether the signalreally originates from penile smooth muscle; validation of the method wouldoffer a most important source of information on penile innervation status,which is necessary for erection.

4 INTRAOPERATIVECLINICAL NEUROPHYSIOLOGY

The authors have demonstrated that with appropriate modifications of methodsit is technically feasible to record in anesthetized patients (a) dorsal root actionpotentials (DRAPs) after pudendal nerve stimulation, (b) pudendal somatosen-sory evoked potentials over the conus, the spinal cord, and the scalp, (c)sphincter muscle EMG responses to sacral ventral root stimulation and motorcortex stimulation, and (d) the bulbocavernosus reflex. Only one of the afore-mentioned techniques has been used extensively enough to gather pertinentinformation regarding the practical relevance of sacral nervous system moni-toring during surgical interventions. However, the techniques are expected tobe valuable safeguards against inadvertent lesioning of nervous structures thatwould lead to some (neurogenic) dysfunction of micturition, defecation, or thesexual response. Further studies are required to clarify these issues.

4.1 BASIC TECHNICAL ASPECTS OF STIMULATION

FOR INTRAOPERATIVE SACRAL MONITORING

In order to obtain bioelectrical signals useful for monitoring purposes in the dif-ferent segments of the sacral neuromuscular system, it is necessary to depolar-ize the nervous system at particular segments. Up to now only electricalstimulation has been appropriate for this purpose. Stimulation can be appliedto either the sensory part or the motor part of the system (afferent versus effer-ent events; Fig. 9.1). At present, most intraoperative monitoring of the sacralsystem has relied on responses evoked from stimulation of the sensory system,apart from recording of anal sphincter muscle responses upon stimulation ofventral spinal roots or the motor cortex.



FIGURE 9.1 Neurophysiological events used to intraoperatively monitor the sacral nervoussystem. Left, “afferent” events after stimulation of the dorsal penile or clitoral nerves and recordingover the spinal cord: (1) pudendal SEPs, traveling waves, (2) pudendal DRAPs, and (3) pudendalSEPs, stationary waves, recorded over the conus. Right, “efferent” events: (4) anal M wave recordedfrom the anal sphincter after stimulation of the S1–S3 ventral roots, (5) anal motor-evoked poten-tials recorded from the anal sphincter after transcranial electrical stimulation of the motor cortex,and (6) bulbocavernosus reflex obtained from the anal sphincter muscle after electrical stimulationof the dorsal penile or clitoral nerves. Reprinted from Deletis, V. (2001). Neuromonitoring. In “Pedi-atric neurosurgery,” 4th ed. (D. MacLeone, ed.), pp. 1204–1213. W.B. Saunders, Philadelphia.



The appropriate peripheral sensory structures that are available for stimu-lating purposes are the two adjacent dorsal penile or clitoral nerves. Thesenerves are stimulated by silver/silver chloride cup EEG-type electrodes (EEGelectrodes) placed on the dorsal surface of the penis or clitoris (this electroderepresenting the cathode). The other electrode (anode) is placed either distallyon the penis (1–2 cm apart from the proximal electrode) or on the adjacentlabia (Fig. 9.2). In small children with short penises, the anode may be attachedon the ventral side of the penis. The dorsal side of the penis must be scrubbedgently with Nuprep (D. O. Weaver & Co., Aurora, CO) before placing electrodesin order to avoid stimulus artifacts. The electrodes are filled with electrodecream and secured appropriately (Tegaderm; Smith and Nephew Medical Lim-ited, Hull, England). The electrode sites are then bandaged with a few layers of

FIGURE 9.2 Lower left, position of the electrodes over the clitoris and labia majora for the stim-ulation of the dorsal clitoral nerves. Lower right, position of the electrode for stimulating the dorsalpenile nerves. R1 = recording BCR from anal sphincter. Upper right, schematics of recording DRAPswith a hand-held hook electrode (R2) over the exposed dorsal sacral roots of the cauda equina.Upper left, intraoperative picture of DRAP recordings.



gauze to prevent them from being displaced when the patient is moved onto theoperating table. Electrode impedances should be kept below 5 kΩ.

As a general rule, stimuli of 20 mA intensity at 0.2 ms duration have beendelivered in procedures involving stimulation of the penis or clitoris (at vari-ous frequencies for different measurements, up to 13.3 Hz).

Stimulation can also be performed at the level of the spinal roots; a hand-held sterile monopolar electrode can be placed under the appropriate roots (orrootlets, after the root is freed from neighboring roots and lifted outside thespinal canal). Square wave pulses of 1 to 2 mA intensity and 0.2 ms durationare delivered (Fig. 9.1, right).

4.2 BASIC TECHNICAL ASPECTS OF RECORDING FOR

INTRAOPERATIVE SACRAL MONITORING

In our practice, bioelectrical activity from the sacral neuromuscular system hasup to now been recorded from the sacral dorsal spinal roots, the spinal cord, thesomatosensory cortex, and the anal sphincter muscle.

Recordings from dorsal spinal roots (dorsal root action potentials, DRAPs)are obtained by hand-held sterile bipolar hook electrodes (after the root is freedfrom neighboring roots and lifted outside the spinal canal). In this case, theelectrode closer to the point of stimulation is the G1 (active) electrode. Epochlengths of 0 to 50 ms are used for these recordings (Figs. 9.1, 9.2).

Recordings of pudendal spinal somatosensory evoked responses (SSEPs, sta-tionary wave) are obtained by a spinal epidural electrode placed over the conus(S2–S4). These potentials are generated by interneurons of the grey matterwithin the S2–S4 segments of the spinal cord. Typically 100 responses are aver-aged together; epoch lengths of 0–50 ms are used (Fig. 9.1).

Recordings of pudendal spinal somatosensory evoked responses (SSEPs, travel-ing wave) are obtained by a spinal epidural electrode inserted anywhere overthe dorsal column of the spinal cord. These potentials are generated by puden-dal afferents traveling within the dorsal columns. Typically 100 responses areaveraged together; epoch lengths of 0–50 ms are used (Fig. 9.1).

To obtain pudendal cerebral somatosensory evoked responses (CSEPs), Screw-type recording electrodes are placed on the scalp 2 cm behind CZ (G1 or activeelectrode) and at FZ (G2 or reference electrode), according to the somatotopicrepresentation in the primary somatosensory cortex related to the International10–20 System of scalp electrode placement. The active electrode is placed in themidline because the sacral segments are represented deep within the mediallongitudinal interhemispheric fissure. For CSEPs, 100–200 traces are typicallyaveraged together. Epoch lengths of 0–200 ms are used.



To record anal sphincter (EMG) responses, either surface-type electrodes orhook wire electrodes can be used. Given the close anatomical relationshipbetween the small sphincter muscle and neighboring larger muscle groups,recording must be selective (e.g., with intramuscular hook wire electrodes) ifthe stimulation technique is “nonselective” (such as in the case of ventral rootstimulation, as a consequence of which neighboring muscles are also excited).When the stimulation procedure is more specific (e.g., in bulbocavernosus orpudendoanal reflex monitoring), the recording may be obtained with properlyattached surface-type electrodes.

Sterile hook wire recording electrodes (Teflon-coated, 76 µm diameter wirewith a 3 mm bare tip) are introduced into the left and right sides of the exter-nal anal sphincter with sterile needles; these are immediately removed carefullyfrom the sphincter (the hooked wires remaining in place). The integrity of theelectrodes can be tested by passing a short train of 50 Hz current at 10 mA andobserving sphincter contraction (if the patient is not paralyzed at the time ofelectrode placement). The electrode impedances of these electrodes should bechecked, although clean recordings are usually still possible with high elec-trode impedances.

The epoch length used for anal sphincter EMG recordings varies accordingto the type of response; either single or few averaged responses can be obtainedupon stimulation (of course, the patient should not be under the influence of amuscle relaxant during this procedure).

4.3 SPECIFIC SACRAL NEUROMUSCULAR SYSTEM

MONITORING PROCEDURES

4.3.1 Pudendal Dorsal Root Action Potentials (DRAPs)

In the treatment of spasticity (e.g., in cerebral palsy), the sacral roots areincreasingly being included during rhizotomy procedures (see Chapter 10).Lang [14] demonstrated that children who underwent L2–S2 rhizotomies hadan 81% greater reduction in plantar/flexor spasticity compared to childrenwho underwent only L2–S1 rhizotomies. But, as more sacral dorsal roots havebeen included in rhizotomies, neurosurgeons have experienced an increasedrate of postoperative complications, especially with regards to bowel and blad-der functions.

In order to spare sacral function, we attempted to identify those sacral dorsalroots that were carrying afferents from pudendal nerves. To do this, we usedrecordings of dorsal root action potentials (DRAPs). Patients were anesthetizedwith isoflurane, nitrous oxide, fentanyl, and a short-acting muscle relaxantintroduced only at the time of intubation. The cauda equina was exposed



through a T12–S2 laminotomy or laminectomy and the sacral roots were iden-tified using bony anatomy. The dorsal roots were separated from the ventralones, and DRAPs were recorded by a hand-held sterile bipolar hooked electrode(the root being lifted outside the spinal canal) (Fig. 9.2). The DRAPs wereevoked by electrical stimulation of the penile or clitoral nerves. One hundredresponses were averaged together and filtered between 1.5 and 2100 Hz. Eachaverage response was repeated to assess its reliability. Afferent activity from theright and left dorsal roots of S1, S2, and S3 was always recorded, along withoccasional recordings from the S4–S5 dorsal roots. DRAP recording was suc-cessfully obtained in the majority of patients. In our first publication [4], theDRAPs were present in the S2 and S3 roots bilaterally in 19 patients, whereasin 7 patients DRAPs were also present in both S1 roots (in 8 patients they werepresent in the S1 root unilaterally). However, the response in the Sl root wasnever larger than the S2 or S3 root responses. The range of amplitudes was2.9–18.3 µV in S1 roots, 3.2–129.9 µV in S2 roots, and 4.6–333 µV in S3 roots.Of special relevance was the finding that in 7.6% of these children, all afferentactivity was carried by only one S2 root (Fig. 9.3, C and F). These findings wereconfirmed by a later analysis of the results of mapping in 114 children (72 male,42 female, mean age 3.8 years) [5]. Mapping was successful in 105 out of 114patients; S1 roots contributed 4.0%, S2 roots 60.5%, and S3 roots 35.5% of theoverall pudendal afferent activity. The distribution of responses was asym-metrical in 56% of the patients (Fig. 9.3, B, C, and F). Pudendal afferent dis-tribution was confined to a single level in 18% (Fig. 9.3, A), and even to asingle root in 7.6% of patients (Fig. 9.3, C and F). Fifty-six percent of thepathologically responding S2 roots during rhizotomy testing were preservedbecause of the significant afferent activity, as demonstrated during pudendalmapping. None of the 105 patients developed long-term bowel or bladdercomplications.

All our results in the early series of dorsal root mapping with 19 patients [4]have been confirmed by analysis of the larger series of 105 patients [5]. Withthis series we showed that selective S2 rhizotomy can be performed safely with-out an associated increase in residual spasticity, while at the same time boweland bladder function are preserved by performing pudendal afferent mapping [14].Therefore, we suggest that the mapping of pudendal afferents in the dorsal rootsshould be employed whenever these roots are considered for rhizotomy in chil-dren with cerebral palsy without urinary retention. Preoperative neurourolog-ical investigation of the children should help in making appropriate decisions;for example, in children with cerebral palsy with hyperreflexive detrusor dys-function, sacral rhizotomy may be considered to alleviate the problem. In anycase, intraoperative mapping of sacral afferents should make selective surgicalapproaches possible and provide the maximal benefit for children with cerebralpalsy.


FIGURE 9.3 Six characteristic examples of DRAPs showing the entry of a variety of pudendal nerve fibers to the spinal cord via S1–S3 sacral roots. (A)Symmetrical distribution of DRAPs confined to one level (S2) or three levels (D). Asymmetrical distribution of DRAPS confined to the right side (B), onlyone root (C or F), or all roots except right S1 (E). Recordings were obtained after electrical stimulation of bilateral penile/clitoral nerves.

209



Our results so far support the hypothesis that the root distribution of affer-ent fibers that are important for the control of micturition may be similar to thedistribution of mucocutaneous afferent fibers from the pudendal nerve. Onlyfurther studies will clarify the complex functional anatomic issues involved.

4.3.2 Pudendal Spinal Somatosensory Evoked Responses (SSEPs)

Recordings were performed in four children of both sexes, 2.5 to 7.0 years ofage. Small-amplitude (up to 1 µV) SSEPs, which were very stable, could berecorded with subdurally placed electrodes over the thoracic spinal cord (trav-eling waves), while a stationary wave could be recorded with a much higheramplitude (up to 10 µV) over the conus region. The latencies of the spinal SEPover the conus region ranged from 6.0 to 10.4 ms (Fig. 9.1, left). The record-ings were made as a pilot study, and thus far only demonstrate the ability toobtain such recordings intraoperatively. Further employment of this techniqueshowed that traveling waves are difficult to record, and successful recording ofa stationary wave necessitates that the electrode be placed strictly over the S2–S4sections of the spinal cord.

4.3.3 Pudendal Cerebral Somatosensory Evoked Potentials (CSEPs)

Well-formed cerebral SEPs with amplitudes of 0.5–0.7 µV were recorded ondorsal penile nerve stimulation throughout spinal neurosurgical procedures intwo adult male patients, 50 and 78 years of age. Stable P40 peaks were obtained.The recordings were made as a pilot study and thus far only demonstrate theability to obtain such recordings intraoperatively. Further employment of thismethod showed that this potential is very sensitive to anesthetics; a formal fea-sibility study has not yet been performed.

4.3.4 Anal Sphincter Motor Response Monitoring

In five children of both sexes, 2.5 to 9.0 years old, anal sphincter muscle EMGresponses were recorded by stimulation of the ventral spinal roots (L5, S1, S2,S3, and S4) to identify ventral roots carrying motor fibers to the sphinctermuscle. Recordings were obtained by surface conductive rubber electrodes(applied para-anally) and intramuscular hooked wire electrodes. In surfacerecordings, no unilateral responses could be identified, and responses werealso obtained on stimulation of the L5 and S1 roots (on stimulation of L5 andS1 roots no adequate responses could be discerned from simultaneous record-ings from intramuscular electrodes). The surface recorded responses were rec-ognized as “nonspecific” (derived from neighboring muscles, most probablyglutei [15]).



The latency of surface recorded responses was, as a rule, shorter than thelatency of responses obtained from intramuscular electrodes, which was between5 and 8 ms. On electrical stimulation of the motor cortex, anal sphincterresponses were recorded in a large group of anesthetized patients without pyra-midal involvement. Because of polysynaptic connections of the corticospinaltract to the α-motoneuron of S2–S4, these responses are moderately sensitiveto anesthetics (Fig. 9.1).

4.3.5 Bulbocavernosus Reflex (BCR) Monitoring

Intraoperative recordings were first performed in 15 neurosurgical patients (11males, 4 females, 2–6 years old). Patients were without sacral dysfunction andwere anesthetized with fenatyl and propofol or nitrous oxide without theinfluence of a muscle relaxant. Recordings from the anal sphincter wereobtained by hooked wire electrodes and were recorded as a single response.Very reproducible responses could be obtained on double-pulse stimulation,the optimum interstimulus interval being found to be 3 ms and the optimumstimulation rate 2.3 Hz. Continuous periods of stimulation and recording forup to 10 min were repeatedly performed with very reproducible results (Fig.9.4). The reflex response was suppressed by the administration of isofluraneand nitrous oxide and was completely abolished by muscle relaxants [16]. Afterthis pilot study, 119 patients were tested, 38 of which underwent surgery with-out risk and 81 of which underwent surgery with risk of damage to sacralstructures. In all, 51 adults (19 to 64 years old, 32 male and 19 female) and68 children (24 days to 17 years old, 30 male and 38 female) took part in thestudy. Patients were anesthetized with propofol, fenatyl, or nitrous oxidewith a short-acting relaxant. Clinically, most patients had mild to moderateupper motor neuron deficits in the lower extremities, and no patient had majorurinary problems. In all patients it was possible to record reproducible reflexresponse with the previously described method. In patients without risk to thesacral system, only a few minutes of the responses were recorded to test theirfeasibility, whereas in the patients at risk, continuous monitoring was con-ducted. The influence of volatile anesthetic was tested in 6 patients. In 3patients, BCR was suppressed by the administration of 1.25% isoflurane for 15 min(Fig. 9.5). Administration of nitrous oxide (60% inspired concentration) for15 min reduced the BCR in 3 patients, and the response was completely abol-ished by muscle relaxant in 2 patients [6].

Preliminary results conducted in 50 patients with a lumbosacral teth-ered cord showed no clear correlation between BCR and postoperativesphincter control. The authors concluded that the complexity of sphincterinnervation and segmental or suprasegmental control probably accounts for thisdiscrepancy [17].



Up to now, close to 250 patients have been monitored using this method. Inthe last 100 patients, a train of four consecutive stimuli [7] was used rather thana double stimulus, providing even more robust responses. Some problems havebeen encountered in female patients in whom the stimulation method is not asrobust as required; this problem needs particular attention from the technician.

5 DISCUSSION AND CONCLUSIONS

The impetus to include intraoperative monitoring of sacral nervous structurescame from concerns over optimizing care for children with cerebral palsy.These were successfully treated for their spasticity by performing selectivedorsal rhizotomy; surgeons have always sought to minimize the side-effects ofthis procedure while maintaining its benefits (benefits being a reduction inmuscle hypertonia, the side-effects being a partial or complete loss of sensory

FIGURE 9.4 Continuous monitoring of the BCR for a period of 10 min showing the stability ofthe BCR’s appearance.



modalities). The first sacral dorsal roots have always been a target for rhizotomyin this procedure, but the S2 dorsal roots have become increasingly consideredfor rhizotomy. Not to treat the S2 dorsal roots is to leave potentially abnormalreflexive circuits that will continue to drive spasticity in the musculature of theleg. For this reason, the lesion zone was extended to include S2 dorsal roots,and the result was a greater reduction in spasticity as compared with children

FIGURE 9.5 The influence of isoflurane (Iso) on the BCR. Note that the response was almost com-pletely blocked when the concentration of 1.25% was administered for 15 min and did not recoveruntil almost 30 min after the isoflurane was discontinued. Reprinted from [6].



in whom the lesion was extended only to the S1 segment. Unfortunately, theextension to include S2 roots was also associated with disorders in micturition.In one group of patients, before DRAP mapping was introduced, 24% experi-enced urinary retention (which was only transient in most children). Althoughmost of these children had both the left and right S2 roots cut, 2 of the childrenhad only one S2 root cut, and they also experienced retention. The selectivedorsal rhizotomy procedure should be performed in young children who arecertainly too young to assess sexual function; they are even too young to becompletely confident that all symptomatic complaints regarding micturition ordefecation and perineal sensation were being relayed. It was this concern overthe preservation of genitourinary afferent function that led us to develop thetechnique of intraoperative neurophysiological identification of the sacral rootsresponsible for perineal sensation. In the first 31 children, neurophysiologicalidentification of roots and rootlets carrying afferent activity from the penile orclitoral nerves led to zero micturition disturbances and allowed for rhizotomyof S2 roots or rootlets not carrying such afferent activity. Therefore, maximumpossible antispastic effects could be achieved. The particularly important lessonwe learned by doing very systematic recordings in S1–S2 and S3 roots bilater-ally (and in some children also S4 and S5 roots) is that although most of ourpatients showed evidence of pudendal afferents in S2 and S3 roots bilaterally,about half of them also showed evidence of some afferent activity in S1 (eitherunilaterally or bilaterally). In slightly more than half of our patients, the rootpotentials were symmetrical, but the pudendal afferents of many were irregu-larly distributed across the sacral roots. In a few of the children the afferentactivity was confined to a single root (either S2 or S3 root). Since this may bethe most important afferent contribution from the genitourinary area, even ifonly the S2 dorsal roots are checked for relevant afferent activity, they shouldnot be sacrificed if they show any such activity. The finding of asymmetrical dis-tribution of fibers that may be confined to a single root is consistent with thework of Junemann et al. [18], who found that the majority of motor fibers forthe urethral sphincter are carried by a single variable lower sacral root. There-fore, for some patients undergoing an operation in the area of the cauda equina,the sacrifice of one single root may have dire functional consequences.

For other neurosurgical procedures in the lumbosacral spinal canal (e.g.,the release of a tethered cord or the removal of a tumor), other authors haveproposed, and in a small series have performed, the identification of motor andsensory nerve roots. This has been achieved through continuous monitoring ofelectromyographic activity in muscles innervated by lumbosacral segments, andthrough monitoring of tibial nerve somatosensory evoked potentials [19]. Inaddition, monitoring pudendal SEPs should provide very relevant complemen-tary information, and, as we have demonstrated, should not be technicallydemanding if the structures are preserved preoperatively. Kothbauer et al. [19]



claim that intraoperative recordings saved operating time by allowing the sur-geon more rapid and decisive preparation than would be possible on ananatomical basis alone, and they also gave the impression that the procedureswere safer. The recordings of spontaneous anal sphincter electromyographicactivity during such operations have been described earlier [20]. To accomplishthe two goals of neurophysiology (i.e., first, immediate identification of struc-tures as functional nervous tissue and their distinction from other tissue; andsecond, continuous monitoring of the function of the relevant nervous struc-tures), a battery of methods needs to be applied, and a whole set of structuresneeds to be assessed bilaterally. Therefore, both the lower sacral segments andsphincter muscles, and also the upper sacral segments and the lumbar seg-ments, need to be included. Also, all these segments and several functionalmodalities need to be monitored more or less simultaneously. The appropriatesetup for each surgical situation would need to be selected on the basis ofanatomical and physiological considerations, and a compromise between thepossible and the necessary would be sought.

Other authors have claimed that continuous EMG recording of bursts ortrains of motor unit potentials or repetitive neurotonic discharges elicited byinjury to the peripheral motor fibers have correlated with postoperative transientor permanent neurological deficit [21, 22] in the area of facial nerves. The pre-dictive value of these “manipulation-evoked” discharges is only based on empir-ical data, but has been proposed to also be of value in the lumbosacral segments[19]. The electrophysiological identification of motor nerves is already an inte-gral part of cranial nerve surgery [22] and should also provide a similar servicein the region of the cauda equina.

Up to now, only recordings of DRAPs have been made in a large number ofsubjects (to identify sacral roots carrying genitourinary afferents), and the elec-trophysiological procedure decreased postoperative voiding disturbances [4, 5].We propose, however, that the other intraoperative electrophysiological record-ings of the sacral neuromuscular system that have been described (spinal SEP,CMAP of sphincter muscles, bulbocavernosus reflex recordings) should proverelevant in surgeries involving the sacral roots, the cauda equina, and the conusand should aid the surgeon in preventing inadvertent damage to these struc-tures. These other procedures have not, however, been performed in an ade-quate number of patients, and their relevance cannot yet be appraised. Themost interesting question is whether monitoring of the bulbocavernosus reflexfor conus and cauda equina surgery could, as we are proposing, replace andeven improve upon separate monitoring of motor and sensory fibers of thelower sacral roots.

As for surgeries involving the spinal cord above the conus, the proceduresof pudendal SSEPs, cortical SEPs, and (possibly) motor evoked potentials of theanal sphincter muscle might be interesting in some selected patient groups.



These would include groups in whom the preservation of sacral function maybe particularly important (for instance, in scoliosis surgery in patients withadvanced neuromuscular diseases who have heavily compromised motor func-tion but no sacral dysfunction).

In other contexts, authors have argued that recordings from the anal sphinc-ter cannot be taken as completely adequate information on the functional statusof the urethral sphincter [18]. Since innervation of both sphincters originatesfrom the same sacral segments (which also provide innervation for the detru-sor), the monitoring of sphincter ani should generally mirror the function ofrelevant urethral structures.

As previously stated, the relatively limited experience with the monitoringof sacral structures cannot as yet prove that surgeries accompanied by suchmonitoring are easier and safer. For the time being, there is anecdotal evidencethat difficult surgical decisions that have relied on the results of intraoperativeneurophysiological measurements have not resulted in unexpected neurologi-cal deficits. Although the techniques described clearly provide the surgeon withadditional information about nerve location and function, the value of thesetechniques must be further defined and documented. As Daube [23] sug-gests, it will be necessary to demonstrate that these techniques indeed saveoperative time, save anesthesia time, or—most importantly—improve out-comes. It will be difficult to demonstrate this without doing a randomized studyof patients who are undergoing surgery with and without such monitoringtechniques.

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7. Rodi, Z., and Vodusek, D.B. (2001). Intraoperative monitoring of bulbocavernous reflex: Themethod and its problems. Clin. Neurophysiol., 112, 879–883.



8. Williams, P.L., Warwick, R., Dyson, M., and Bannister, L.H. (Eds.) (1989). “Gray’s anatomy.”Churchill Livingstone, Edinburgh.

9. Donker, P.M., Droes, J., and Van Ulden, B.M. (1976). Anatomy of the musculature and inner-vation of the bladder and the urethra. In “The scientific foundation of urology: Volume 2” (D.I.Williams, and G.D. Chisholm, eds.), pp. 32–39. Year Book Medical Publishers, Chicago.

10. Vodusek, D.B., and Light, J. K. (1983). The motor nerve supply of the external urethral sphinc-ter muscles: An electrophysiologic study. Neurourol. Urodynam., 2, 193–200.

11. Henry, M.M., and Swash, M. (1992). “Coloproctology and the pelvic floor,” 2nd ed. ButterworthHeinemann, Oxford.

12. Vodusek, D.B., Fowler, C.J., Deletis, V., and Podnar, S. (2000). Clinical neurophysiology ofpelvic floor disorders. In “Clinical neurophysiology at the beginning of the 21st century” (Z.Ambler, S. Nevsímalová, Z. Kadanka, and P.M. Rossini, eds.), pp. 220-227 (Clinical Neuro-physiology, Suppl. 53). Elsevier Science B.V., Amsterdam.

13. Lundberg, P.O., Brackett, N.L., Denys, P., Chartier-Kastler, E., Sønksen, J., and Vodusek, D.B.(2000). Neurological disorders: Erectile and ejaculatory dysfunction. In “Erectile dysfunction”(A. Jardin, G. Wagner, S. Khoury, F. Guiliano, H. Padma-Nathan, and R. Rosen, eds.), pp. 593-645. Health Publication, Plymouth, U.K.

14. Lang, F.F., Deletis, V., Valasquez, L., and Abbott, R. (1994). Inclusion the S2 dorsal rootlets infunctional posterior rhizotomy for spasticity in children with cerebral palsy. Neurosurgery, 34,847–853.

15. Vodusek, D.B., and Zidar, J. (1988). Perineal motor evoked responses. Neurourol. Urodynam.,7(3), 236–237.

16. Vodusek, D.B., Deletis, V., and Kiprovski, K. (1993). Intraoperative bulbocavernosus reflexmonitoring: Decreasing the risk of postoperative sacral dysfunction. Neurourol. Urodynam.,12, 425–427.

17. Sala, F., Krzan, M.J., Epstein, F.J., and Deletis, V. (1999). Specificity of neurophysiologicalmonitoring of the lumbosacral nervous system during tethered cord release: A preliminaryreport. Childs Nerv. Syst., 15, 426.

18. Junemann, K.P., Schmidt, R.A., Melchior, H., and Tanagho, E.A. (1987). Neuroanatomy andclinical significance of the external urethral sphincter. Urol. Int., 42, 132–136.

19. Kothbauer, K., Schmid, U.D., Seiler, R.W., and Eisner, W. (1994). Intraoperative motor andsensory monitoring of the cauda equina. Neurosurgery, 34(4), 702–707.

20. James, H.E., Mulcahy. J.J., Walsh, J.W., and Kaplan, G.W. (1979). Use of anal sphincter elec-tromyography during operations on the conus medullaris and sacral nerve roots. Neurosurgery,4(6), 521–523.

21. Daube, J.R. (1991). Intraoperative monitoring of cranial motor nerves. In “Intraoperative neu-rophysiologic monitoring in neurosurgery” (J. Schramm, and A.R. Møller, eds.), pp. 246–267.Springer-Verlag, Berlin.

22. Harder, S., Daube, J.R., Ebersold, M.J., and Beatty, C.W. (1987). Improved preservation offacial nerve function with use of electrical monitoring during removal of acoustic neuromas.Mayo Clin. Proc., 62, pp. 92–102.

23. Daube, J.R. (1994). Comment on Kothbauer, K., et al. (1994). Intraoperative motor and sen-sory monitoring of the cauda equina. Neurosurgery, 34(4), 702–707.


C H A P T E R 10

Sensory Rhizotomyfor the Treatmentof Childhood SpasticityRICK ABBOTT

Hyman-Newman Institute for Neurology and Neurosurgery, Beth Israel Medical Center, New York

1 Introduction2 Modern Development of Selective Dorsal Rhizotomy3 Physiologic Basis of Current Techniques4 Outcome5 ConclusionReferences

ABSTRACT

Sensory rhizotomy has been used for the past century to treat spasticity. Over the lastseveral decades there has been an evolution in the technique, and a clearer idea ofexpected outcomes has been gained. This chapter will describe the evolution in sur-gical techniques of sensory rhizotomy as well as reported results when using thesenewer techniques to treat childhood spasticity.

1 INTRODUCTION

Selective functional, dorsal (or posterior) rhizotomy (SDR) has become anincreasingly popular means of treating children with congenital spastic diplegicand quadriplegic cerebral palsy. Sensory rhizotomies were first used in the latenineteenth century [1]. In the 1960s, serious work began on refining this tech-nique, and SDR was introduced in the mid-1970s. Several papers have since beenpublished describing the short- and intermediate-term benefits as well as com-plications seen in children receiving selective functional rhizotomies [2–8].This chapter will describe the physiology supporting SDR as well as the com-plications and outcome reported in children who have been treated with it.



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2 MODERN DEVELOPMENT OF SELECTIVE

DORSAL RHIZOTOMY

The bulk of SDRs performed in North America are based on the surgical tech-nique developed by Fasano [9]. In 1976, he described a modification of earlierforms of rhizotomy that was based on the studies by DeCandia of spinal reflexesin cats [10, 11]. DeCandia had shown that stimulation of the dorsal root withtrains of 15 Hz or greater would cause a progressive depression in the evokedreflex motor response in normal states of spinal reflex circuit excitability. Thisdepression did not occur, however, in the context of an upper motor neuroninjury. Rather, a one-for-one compound motor action potential (CMAP) wasseen when sensory roots were stimulated in animals with upper motor neuroninjuries. Fasano applied these findings to children with spasticity and foundthat some sensory fibers, when stimulated with 30 to 50 Hz trains, would trig-ger one CMAP response for each stimulus, with an associated muscle contrac-tion. Other sensory fibers, when stimulated with an identical train, did not.Instead, there was a rapid diminution of response with an abolishment of themotor response within several pulses of initiation of the stimulus train. Fasanodescribed the first type of response pattern as abnormal in that it identified acircuit whose controlling interneuronal pool had lost the inhibitory influenceof descending upper motor neurons. Thus a circuit was identified that mediatedthe spasticity present (an abnormal root or rootlet). The second type of patternidentified normal roots or rootlets. He described other patterns of response asbeing associated with abnormal roots or rootlets (i.e., tetanic contraction lastinglonger than the duration of stimulation and/or spread of muscle activation out-side the myotome of the spinal segment whose sensory root was being stimu-lated, or to another limb) (Fig. 10.1). Fasano stimulated the sensory roots of thecauda equina, labeling them as normal or abnormal in their response pattern toa 50 Hz stimulation train. Abnormal roots were subdivided into their componentrootlets, which in turn were stimulated (Fig. 10.2) (see also color plate), andabnormally responding rootlets were cut. Fasano coined the term functionaldorsal rhizotomy to describe the technique. This is the rhizotomy techniquethat most centers in North America have used as a starting point in treatingspasticity.

SDR was introduced to North America by Peacock, who also can be creditedwith improving the procedure’s safety [12]. He noted that the procedure as per-formed by Fasano put the urologic system at significant risk because when oper-ating at the level of the conus there can be difficulty in identifying the functionallevel of the sensory nerve roots. For that reason, he moved the site of thesurgery to the lumbosacral canal, which allowed for a more secure identifica-tion of the midsacral nerve roots.


Sensory Rhizotomy for the Treatment of Childhood Spasticity 221

This concern was underscored in the early 1990s as centers began to reporton occurrences of postoperative urologic dysfunction in children undergoingrhizotomies. As a consequence, Deletis et al. developed a mapping technique toidentify nerve roots involved in micturition reflexes, and a decrease in post-operative urologic dysfunction was reported [13, 14] (see Chapter 9). In 1987we reported on the utility of multichannel EMG recording in monitoring for thespread of muscle activity during nerve root stimulation [15].

As already explained, there seems to be a relationship between spasticity andhyperactive stretch reflexes. Consequently, much of the evolution in sensoryrhizotomy has centered on attempting to identify sensory roots or their subdi-visions that are participating in these hyperactive reflexes. In the 1950s,Magladery described the effect of a conditioning compound muscle actionpotential (CMAP) triggered by an afferent sensory stimulus on the amplitudeof subsequent evoked CMAPs [16]. The amplitude of these CMAPs (so-calledH reflexes) can be expressed as a ratio, and a H reflex recovery curve (H2/H1)

FIGURE 10.1 Eight-channel EMG recordings showing spreading of activity in (top to bottom)right hip adductors, quadriceps, femoris, hamstrings, and gastrocnemius muscles in response tostimulation of the right L5 sensory nerve root. (Reprinted from Abbott, R. (2001), Sensory rhizo-tomy for the treatment of childhood spasticity, in “Pediatric neurosurgery: Surgery of the develop-ing nervous system,” 4th ed. (P.G. McClone, ed.), pp. 1053–1062, W.B. Saunders Company,Philadelphia.)


222 Rick Abbott

can be generated. In normal individuals, an attenuation in the response to thesecond (or later) sensory stimuli is expected when the stimulation train is above10 Hz due to recurrent inhibition by the interneuronal pool on the α-motoneu-ron. Mayer and Mosser [17] described a 82.3% reduction in responses followingCMAPs with a 10-Hz stimulation train in children aged 3–7 years. Nishida et al.[18] described a surgical technique using the H2/H1 reflex recovery curve thatwas established using a subthreshold sensory stimulation train. They used asomewhat arbitrary figure of 50% as the amount of expected diminution inamplitude of CMAPs following the initial CMAP. Abnormal roots were thosefound to not have the expected 50% or greater diminution. Logigian et al. [19]described a technique of stimulating the sensory roots first near the cord andthen at a distance. If the latency of the CMAP increases as the root is stimulatedat greater distances from the cord, the response is felt to be reflexive [19]. Theseroots are then separated into their component rootlets, and these are stimulated.The amplitude of the response is then graded, and those with the greatestresponse are cut (typically 40–70% of the tested rootlets at a given level).

There has been a tendency for centers performing SDRs to modify and intro-duce subtle variations to the technique. Almost uniformly, surgeons todayreport fewer rootlets being cut. Figures between 20 and 60% are commonly

FIGURE 10.2 Rootlet of L5 sensory root being held by stimulator probes away from rest of sen-sory root (see also color plate).



cited, as opposed to 80% cited in earlier papers. A paper released in the mid-1990s by Steinbok et al. [20] described the evolution of their group’s SDR tech-nique and the rationale behind it. As their experience grew, they modified thedescriptor of an abnormal CMAP response to a rootlet being stimulated. Cur-rently, an abnormal response consists of activation of muscles in the contralat-eral leg or, more importantly, in the upper extremities. They made this modificationafter noting the pattern of muscle contraction in four nonspastic childrenundergoing surgery for a tethered spinal cord. The exposed sensory roots inthese children were stimulated when the same protocol as their rhizotomy pro-tocol was used. There was a spread in muscle activation to involve muscles out-side of the nerve root’s myotome, but it was unusual to see contractions in thecontralateral limb, and no muscle contraction was seen in the upper extremity.After using this modification, Steinbok et al. observed no change in functionaloutcome, although they have experienced a greater amount of postoperative in-toeing, which they attribute to an imbalance in the surgery’s effect on the toneof the medial and lateral hamstrings.

Phillips and Parks [21] have described a grading system of “abnormal”responses. Grade 0 is Fasano’s normal response (unsustained response to astimulus train). Grade 1 represents a sustained response in the root’s myotome,and grade 2 represents a spread of activity to muscles innervated by roots adja-cent to the one being stimulated. Grade 3 represents a spread of activity to mus-cles innervated by roots distant from the one being stimulated, and grade 4represents a spread to muscles in the contralateral limb [21]. This group advo-cates lesioning rootlets with grade 3 and grade 4 responses, and most centersperforming conventional rhizotomies do the same today.

3 PHYSIOLOGIC BASISOF CURRENT TECHNIQUES

SDR is a deafferentation procedure that is felt to alter the modulating milieu ofthe interneuronal pool responsible for controlling the excitability of the α-motoneurons. One of this pool’s primary functions is to modulate the patternand reactivity of the spinal cord’s reflex circuitry [22–24]. The pool receivesinhibitory innervation from Ia afferents, flexor reflex afferents, and high-thresholdafferents (secondary muscle afferents, joint receptor afferents, and cutaneousreceptor afferents) [23–26]. Descending fiber tracts from the brain as well assegmental spinal afferents, spinal propriospinal fibers, and Renshaw fibers pro-vide an excitatory influence on the pool [23, 27–32; Fig. 10.3A]. When eitherthe spinal cord or the brain is injured, the excitatory and inhibitory influenceson the interneuronal pool become unbalanced, and spasticity can result ifinhibitory influences outweigh excitatory ones, resulting in a net amplification


224 Rick Abbott

of the reflexive output of α-motoneurons (Fig. 10.3B). The cutting of Ia fibersto offset the lack of descending fiber input on the α-motoneurons brings theinfluences on the interneuronal pool back into balance. The SDR seeks to targetIa fibers that are feeding into a segment of the interneuronal pool that is unbal-anced because of a decrease in descending, excitatory influences.

Unfortunately, as eloquent as this rationale seems, operative observationshave not consistently supported it. We reported in 1990 that the evoked pat-tern of muscle contraction in response to repetitive electrical stimulation ofsensory roots varies from stimulation to stimulation [33]. Weiss and Schiff [34]reported on similar findings in their paper in 1993. If the theory is correct,repeated stimulation of a sensory root after an appropriate interval for recoveryshould evoke the same abnormal response, but this was by no means the case.Although some of the variation seen was undoubtedly due to variation in stim-ulator output, subsequent reports support other conclusions. Cohen and Webster[35] reported on 22 patients undergoing SDR, stating that they were unable toelicit a “normal” response to sensory root stimulation in any of the patients.

FIGURE 10.3 (A) Normal circuit modulating reactivity of reflex circuit. (B) Amplification of cir-cuit as a result of loss of upper motor neurons.

DESCENDING CORTICOSPINALTRACTS

INTERNEURONALPOOL

SENSORY

AFFERENTS

a-MOTONEURON

B

A

DESCENDING CORTICOSPINALTRACTS

INTERNEURONALPOOL

SENSORY

AFFERENTS

a-MOTONEURON



In the same paper they also described the results of stimulating the sensoryroots in a nonspastic patient. They were unable to record a so-called normaldecremental motor response, as would be expected when stimulating a normalsensory root. Steinbok et al. [36] reported on 60 consecutive spastic patientswho had 680 roots tested; 99.4% failed to demonstrate a diminution in motorresponse to a 50 Hz stimulus train applied to the sensory roots. Additionally,they used the same stimulation parameters on 4 nonspastic children, stimu-lating a total of 11 roots. They found an abnormal pattern of response in 6 outof 11, and the remaining 5 roots showed the expected diminution of responseto the stimulus train. Finally, Logigian et al. [19] showed that the elicited pat-tern of responses in some patients was probably due to direct activation of sur-rounding motor neurons and that random cutting of rootlets was as efficaciousas directed lesioning (although they used different criteria to determine whatwas cut and what was preserved). Clearly, more understanding of the normaland injured system is required before we can securely postulate what exactlywe are accomplishing when we use evoked motor activity in response to sen-sory root or rootlet stimulation to label what should be cut and what shouldbe preserved.

4 OUTCOME

In the last decade, several papers have discussed the outcome in children withspastic cerebral palsy treated with SDR. One striking finding in all the papers isthat SDR is effective in decreasing spasticity and that this reduction appears tobe permanent. The experience in South Africa has been reviewed by Peter andArens [6]. They examined 104 children 2 to 12 years after they had undergonean SDR and found that 95% experienced a long-term, persistent reduction intone. Cahan et al. [37] used an instrumented gait analysis to examine 14patients and found that the EMG signature of spasticity seen in preoperativetesting had disappeared in the postoperative testing done 6 to 14 months aftertheir surgery. Park et al. [4] found that SDR “always reduced spasticity” inpatients, and Cohen and Webster [35] described “an immediate and significantreduction in muscle tone in the lower extremities of every patient” after theyunderwent an SDR. Steinbok et al. [8] used a myotome to examine 50 patientsbefore and after undergoing an SDR and found that there was a significantdecrease in tone in the lower extremities and that this decrease persisted for thefirst year after their surgeries. Peacock and Staudt [5] used a modified Ashworthscale to assess tone in 25 patients who had received rhizotomies for their spas-ticity; they found that every child demonstrated a normalization of tone andloss of clonus after surgery. We looked at 49 of our patients 6 months and 1 yearafter they had undergone an SDR and found that they had experienced a


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statistically significant drop in hypertonia by 6 months after their surgery andthat this drop persisted at 1 year [2]. We have since been able to examine thesechildren at their 5 year surgical anniversary, and there have been no statisticallysignificant changes in the tone of their lower-extremity musculature. Severalchildren did experience transient increases in tone because of a noxious stim-ulus such as a dislocated hip or a viral illness. After the pain abated, however,the tone returned to its postrhizotomy, premorbid state without any furthertreatment.

A common way to measure the impact of treatment on children with cere-bral palsy is to record the available range of passive motion at a given joint(goniometric measurement), and most papers publishing outcome informationin children treated with SDR have followed this convention. Peacock and Staudt[38] found that patients’ available ranges improved in the hamstrings (but thisdid not reach clinical significance as defined by Stuberg [39]) and in the plan-tar flexors. Children treated at Bristish Columbia Children’s Hospital inVancouver experienced significant improvement in goniometric measurementof the passive range of motion of the hip adductors (hip abduction), hamstrings(knee extension), and ankle plantar flexors (ankle dorsiflexion), but the ham-string’s available range tailed off between 6 and 12 months [8]. Nishida’spatients had significant improvement 2 years after their surgeries in the avail-able range of the hip adductors, knee flexors, hamstrings, and plantar flexors[18]. Our patients showed a statistically significant decrease in range limitationin the hip adductors and hamstrings at 1 year post rhizotomy, and this has per-sisted at 5 year follow-up [2]. We also found that the available range for move-ment of the hamstring muscle is vulnerable to deterioration over time in boththe diplegic and quadriplegic groups. Although this finding may not be clini-cally significant in a child who is wheelchair bound, it can have a great impacton ambulation in a higher-functioning child, and it can be particularly prob-lematic in children who are not being watched by either a therapist or a trainedparent, emphasizing the importance of having an ongoing program of stretch-ing the leg’s musculature.

Although documentation of the muscle tone and passive movement is help-ful in quantifying the procedure’s impact, it is the procedure’s effect on func-tion that truly measures the utility of the procedure in the management ofchildhood spasticity. Early on, most facilities created in-house measurementtools to quantify change in a child’s ability to assume and maintain functionallyimportant positions used in the children’s therapy sessions. Peacock andStaudt [5], using such a system, found that five out of nine children requiredless support to sit, six out of nine improved in their ability to move from akneeling to a half-kneeling position, and four out of nine improved in their abil-ity to rise from a seated position to standing. Twenty-nine of their patientstreated in South Africa were examined by Berman 4–14 months after SDR [40].



She found that 27 could maintain a long sitting position better after theirsurgery, while 19 improved in side sitting, 24 in half-kneeling, and 15 in stand-ing. We used a similar measure after dividing our patients into subgroups ofchildren who preoperatively could walk (walkers), quadriped-crawl (crawlers),or at best could only drag themselves about the room (nonlocomotors) [2]. Ofthe 41 patients followed, 11 were walkers, 11 were crawlers, and 19 were non-locomotors. Of the 11 walkers, 2 improved in long sitting, 1 improved in sidesitting while 3 declined, 5 improved in half-kneeling, and 2 improved in stand-ing. With regards to the crawlers, 7 improved in long sitting while 1 declined,9 improved in side sitting, 10 improved in half-kneeling, and 9 improved instanding. Of the nonlocomotors, 4 improved in long sitting with 2 declining, 5 inside sitting with 3 declining, 8 in half-kneeling with 3 declining, and 4 in stand-ing with 2 declining.

Another way to measure the functional impact of SDR is to analyze the chil-dren’s gait pattern before and after surgery using computerized gait analysis sys-tems. Several centers have done this and have found that the major improvementexperienced by these children is an increase in the stride length due to anincreased ability to extend the knee and/or hip. Adams et al. [41] found thisimprovement to be double that which would be expected with normal matura-tion over a comparable length of time. Boscarino et al. [42], in addition to doc-umenting an increase in stride length, found that there was an increase in theamount of pelvic tilt, presumably due to an asymmetrical effect of the rhizo-tomy, with the hip extensors experiencing a greater reduction in tone than thehip flexors. Both of these groups also found that dorsiflexion at the anklesduring the swing phase of gait improved after surgery. After documenting a sig-nificant increase in valgus deformity during the terminal stance phase of the gaitcycle, Adams et al. also recommended an ankle-foot orthotic to prevent hindand forefoot eversion. He also recommended the inclusion of a dorsiflexionstop to deal with a weakness in the plantar flexors and to control the forwardmomentum of the tibia during the stance phase.

By the mid-1990s, several validated methods had been made available to mea-sure children’s functional capability as well as the degree of assistance theyrequire in the management of daily activities. The Pediatric Evaluation Disabil-ity Index (PEDI) and the Functional Inventory Measure for Children (WeeFIM)are two such tools that can be used to measure a child’s independence or needfor assistance in activities of daily living. Dudgeon et al. [43] followed 16 spas-tic diplegics for a year after their SDRs; all 16 showed improvement in theirmobility scores, and 13 out of 16 improved in their self-care scores. Dudgeon alsoserially examined 5 spastic quadriplegics and found that the changes seen inthis group were not as dramatic as those seen with the spastic diplegics. Bloomand Nazar [44] looked at 8 spastic diplegics and 8 spastic quadriplegics, alsousing the PEDI, and found a significant improvement in self-care scores for


228 Rick Abbott

both groups. The WeeFIM was used by Nishida et al. [18] to study a group ofspastic quadriplegics who had undergone an SDR. They found that the childrenimproved most in bowel and bladder function. They also studied a group ofspastic diplegics undergoing the surgery and found that the greatest improve-ment was in the mobility index. Surgeons have also reported improvement inupper limb function for children after rhizotomies. Steinbok et al. [8] foundthat 26 out of 39 patients experienced improvement in upper limb function,and Kinghorn [45] found that for 7 children with increased and disabling tonein their upper extremities, 6 had an improvement in tone to such a degree as toallow for an improvement in function.

5 CONCLUSION

It seems clear at this point that selective dorsal rhizotomies reliably reduce spas-ticity and that this reduction is permanent. There is increasing evidence thatthis reduction also translates into improvement in function. What remainsunclear are the physiologic explanation for this treatment’s effect and the bestway to perform the treatment. Although there can be little doubt that selectiveposterior rhizotomy is a valid treatment for spastic cerebral palsy, I would antic-ipate a further evolution in the technique as our understanding of the treat-ment’s effect on the nervous system’s physiology grows.

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3. Fasano, V.A., Broggi, G., Zeme, S., Lo Russo, G., and Sguazzi, A. (1980). Long-term results ofposterior functional rhizotomy. Acta Neurochir. Suppl. (Wien), 30, 435–439.

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20. Steinbok, P., Gustavsson, B., Kestle, J.R., Reiner, A., and Cochrane, D.D. (1995). Relationshipof intraoperative electrophysiological criteria to outcome after selective functional posteriorrhizotomy. J. Neurosurg., 83, 18–26.

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28. Jankowska, E., Lundberg, A., and Roberts, W. (1974). A long propriospinal system with directeffects on motoneurones and on interneurones in the cat lumbosacral cord. Exp. Brain Res., 21,169–194.

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30. Lundberg, A. (1964). Supraspinal control of transmission in reflex paths to motoneurones andprimary afferents. In “Physiology of spinal neurones” (J.C. Eccles, ed.), pp. 197–221. Elsevier,Amsterdam.

31. Nathan, P., and Smith, M. (1959). Fasciculi proprii of the spinal cord in man: Review of pre-sent knowledge. Brain, 82, 610–668.

32. Stelzner, D. (1982). The role of the descending systems in maintaining intrinsic spinal func-tion: A developmental approach. In “Brainstem control of spinal mechanisms” (B. Sjolund,ed.), pp. 297–321. Elsevier, Amsterdam.

33. Abbott, R., Deletis, V., Spielholz, N.I., Wisoff, J.H., and Epstein, F.E. (1990). Selective poste-rior rhizotomy, pitfalls in monitoring. In “Concepts of pediatric neurosurgery” (A. Marlin, ed.),pp. 187–195. Basel: Karger.

34. Weiss, I., and Schiff, S. (1993). Reflex variability in selective dorsal rhizotomy. J. Neurosurg.,79, 346–353.

35. Cohen, A., and Webster, H. (1991). How selective is selective posterior rhizotomy. Surg.Neurol., 35, 267–272.

36. Steinbok, P., Langill, L., Cochrane, D.D., and Keyes, R. (1992). Observations on electrical stim-ulation of lumbosacral nerve roots in children with and without lower limb spasticity. ChildsNerv. Syst., 8, 376–382.

37. Cahan, L.D., Adams, J.M., Perry, J., and Beeler, L.M. (1990). Instrumented gait analysis afterselective dorsal rhizotomy. Dev. Med. Child Neurol., 32, 1037–1043.

38. Peacock, W.J., and Staudt, L.A. (1991). Selective posterior rhizotomy: Evolution of theory andpractice. Pediatr. Neurosurg., 17, 128–134.

39. Stuberg, W., Fuchs, R., and Miedaner, J. (1988). Reliability of gonometric measurements ofchildren with cerebral palsy. Dev. Med. Child Neurol., 30, 657–666.

40. Berman, B., Vaughan, C., and Peacock, W. (1990). The effect of rhizotomy on movement inpatients with cerebral palsy. Am. J. Occup. Ther., 44, 511–516.

41. Adams, J., Cahan, L., Perry, J., and Beeler, L. (1995). Foot contact pattern following selectivedorsal rhizotomy. Pediatr. Neurosurg., 23, 76–81.

42. Boscarino, L., Ounpuu, S., Davis, R., Gage, J., and DeLuca, P. (1993). Effects of selective dorsalrhizotomy on gait in children with cerebral palsy. J. Pediatr. Orthop., 13, 174–179.

43. Dudgeon, B., Libby, A., McLaughlin, J., Hays, R., Bjornson, K., and Roberts, T. (1994).Prospective measurement of functional changes after selective dorsal rhizotomy. Arch. Phys.Med. Rehabil., 75, 46–53.

44. Bloom, K.K., and Nazar, G.B. (1994). Functional assessment following selective posterior rhi-zotomy in spastic cerebral palsy. Childs Nerv. Syst., 10, 84–86.

45. Kinghorn, J. (1992). Upper extremity functional changes following selective posterior rhizo-tomy in children with cerebral palsy. Am. J. Occup. Ther., 46, 502–507.


FIGURE 10.2 Rootlet of L5 sensory root being held by stimulator probes away from rest of sensory root.

FIGURE 16.1 A three-dimensional artist's rendition of the structures involved in surgery for movement disorders. The light greenish blue structure on the left is the globus pallidus (GPi and GPe). The large grey structure on the right is the thalamus, and the small dark green structure is the subthalamic nuclei (STN). The medial edge of the STN is only 6.0 m m from the midline of the brain. With the trajectories that our group uses in the operating room, we encounter around 10.0 m m of GPi, 11.0 m m of VIM, and 5.0 m m of STN. Modified from [117].

C H A P T E R 11

NeurophysiologicalMonitoring During PedicleScrew PlacementRICHARD J. TOLEIKIS

Department of Anesthesiology, Rush-Presbyterian-St. Luke’s Medical Center,Rush University, Chicago, Illinois

1 Introduction2 Techniques for Assessing Nerve Root Function

and Pedicle Screw Placement2.1 Sensory Pathway Assessment Techniques 2.2 Motor Pathway Assessment Techniques2.3 Anesthetic Management for Motor Techniques2.4 Factors That Can Contribute to

False-Negative Findings2.5 Impedance Testing

3 Personal Experience4 ConclusionsReferences

ABSTRACT

The use of pedicle screws for spinal stabilization has become commonplace duringvarious spinal surgical procedures. However, the placement of these screws is largelydone blindly, and even in the hands of experienced surgeons, the incidence of mis-placed pedicle screws resulting in neurological impairment has been reported to bequite high, despite the use of surgical inspection and imaging techniques. Althoughnew imaging techniques have been developed that may help to reduce the incidenceof misplaced hardware, the equipment needed to implement their usage is generallycostly, and the techniques themselves are still not developed to the point where theyare free from error. As a result, surgeons and clinical neurophysiologists have usedvarious electrophysiological monitoring techniques for assessing nerve root functionand pedicle screw placements. To be widely and effectively used, these techniquesmust meet certain criteria; the strengths and limitations of each of the techniques willbe discussed in terms of these criteria. On the basis of the author’s experience and


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232 Richard J. Toleikis

outcome data, the combined use of spontaneous and triggered myogenic activity forintraoperative monitoring purposes satisfies all the criteria that a monitoring tech-nique should meet. This technique is cost-effective and improves surgical outcomes.

1 INTRODUCTION

Through the ages, various treatments for spinal deformity have evolved. In1962, Harrington [1] ushered in the revolutionary use of metallic, internal fix-ation devices for spinal deformity when he reported on the use of a distractionrod construct for the treatment of scoliosis. In 1982, Luque [2] demonstratedhow spinal deformity could be corrected by the use of segmental fixation andthe application of transverse forces. In the thoracolumbar region of the spine,spinal instrumentation constructs consisting of hooks and rods have nowbecome the standard of care for the surgical management of degenerative spinaldisease and traumatic insults. In the lumbosacral region, it has become verypopular to use pedicle screws rather than hooks to hold the rods in place forthe purpose of segmental transpedicular fixation.

Although pedicle screws can be placed in the thoracic and lumbosacralspine, they are generally placed in the most caudal segments of the spine:L2–S1. The cross-sectional area of the pedicles is smaller in the thoracic seg-ments of the spine. Because of this, and because it is common for spinal insta-bilities to occur in the lumbosacral region, it is unusual for pedicle screws to beplaced in the thoracic region. From a monitoring perspective, it is important toremember that the spinal cord ends in the conus medullaris at about the T12–L1level of the spine. Therefore, the placement of pedicle screws below these levelspotentially places nerve root rather than spinal cord function at risk.

Proper placement of pedicle screws requires that a surgeon be extremelyknowledgeable about the anatomical characteristics of the thoracic, lumbar,and sacral vertebrae. Despite the use of anatomical landmarks and fluoroscopy,the placement of pedicle screws is largely done blindly. Ideally, they should beplaced so that they pass through the pedicle with about 1 mm to spare on boththe medial and lateral walls and without any breach of the pedicle walls. Inaddition, they should be placed well into the vertebral bodies without anybreach of the vertebral body walls. Nerve roots tend to position themselves nearthe medial and inferior aspects of the pedicles as they exit the spinal canalthrough the spinal foramen. Therefore, screws that are placed so that they pro-trude or are exposed from the medial or inferior pedicle walls can cause nerveroot irritation or injury.

In preparation for the placement of pedicle screws, markers are generallyplaced into the pedicles in order to visualize, via radiographs, the trajectoriesthat the pedicle screws will take. These trajectories may place nerve roots at risk


Neurophysiological Monitoring During Pedicle Screw Placement 233

for injury, because both lateral and anterior–posterior radiographs are subjectto reading errors. As a result, undesirable medial placements of both markersand screws may not be identified. [3, 4]. Such readings are followed by removalof the markers and tapping of the holes made by the markers. These holes canthen be palpated to detect holes in the pedicle walls. The pedicle screws are thenplaced. This placement can result in fractures of the pedicle, breakthroughs ofthe pedicle walls, and/or extrusion of pedicle fragments. Even in the hands ofexperienced surgeons, the current literature reports pedicle cortical perfora-tion rates that have ranged from 5.4 to 40% [5–11]. Such events may go unde-tected unless the pedicle walls are visualized. However, most surgeons arereluctant to routinely visualize screw placements unless this action is war-ranted, since doing so would require that the surgeon do multiple lamino-tomies. This is time-consuming, and these additional procedures by themselvescould also affect postoperative outcome. However, despite the use of surgicalinspection and imaging techniques, misplaced screws have still been frequentlyassociated with neurological functional impairment. The incidence has rangedfrom 1% to more than 11% [12–15].

New imaging technologies aimed at reducing these incidences continue toevolve. Thus far, they have been somewhat cumbersome, costly, and time-consuming, and the end result is that they are still not free of error [16]. There-fore, existing electrophysiological techniques have been used, as well as othersthat have evolved for monitoring neurological function during pedicle screwplacement and for assessing these placements. They include mixed nervesomatosensory evoked potentials (SEPs), dermatomal somatosensory evokedpotentials (DSEPs), and techniques that rely upon both spontaneous and trig-gered myogenic activity. In addition, the measurement of electrical tissueimpedance has been suggested as another means for assessing placements.Other techniques, which include transcranial and spinal stimulation, can alsobe used to test nerve root function during pedicle screw placement; however,although feasible, these techniques are rarely used for this purpose.

2 TECHNIQUES FOR ASSESSING NERVE ROOTFUNCTION AND PEDICLE SCREW PLACEMENT

All nerve roots consist of both sensory and motor fibers. The monitoring tech-niques that are used to assess nerve root function during surgery produce eithersensory or motor responses. Sensory responses that are mediated by a singlespecific nerve root can be elicited by stimulating a specific body surface areaknown as a dermatome. Motor activity that is mediated by a single specificmotor nerve root can elicit myogenic responses from a group of muscles knownas a myotome. Therefore, the responses that are acquired to assess the sensory



and motor function of a single nerve root are known as dermatomal andmyotomal responses, respectively.

There are certain criteria that monitoring techniques should meet if they areto be widely and effectively used to assess pedicle screw placements and pre-serve nerve root function. First of all, implementation of the techniques shouldbe practical; in other words, they should not require special equipment orexpertise. Otherwise, these factors will be a deterrent to their use. For economicand practical reasons, the techniques should utilize standard equipment thatmay already be used for monitoring purposes, they should be easy to perform,and the anesthetic requirements should not be unusual. Second, the techniquesmust be effective. They should provide an instantaneous indication of nerveroot irritation in order to prevent injury or further damage of a nerve root thatis already irritated. They should also be able to detect the presence of a mis-placed screw that is not causing nerve root irritation but that may have thepotential to do so. Finally, they should produce accurate results that make a dif-ference in patient outcomes and that are cost-effective. A discussion of each ofthe following techniques will address these requirements.

2.1 SENSORY PATHWAY ASSESSMENT TECHNIQUES

2.1.1 Somatosensory Evoked Potentials (SEPs)

Since the late 1970s, mixed nerve somatosensory evoked potentials (SEPs) havebeen used to monitor spinal cord function during spinal instrumentation pro-cedures in order to minimize the probability of postoperative neurologicaldeficits [17–20]. SEPs are elicited by stimulating a peripheral nerve at a distalsite: typically the median or ulnar nerves at the wrist for acquiring SEPs fromthe upper extremities, and the posterior tibial nerve at the ankle or the peronealnerve at the fibular head for acquiring lower-extremity SEPs. The ascendingsensory volley that contributes to the SEP enters the spinal cord through dorsalnerve roots at several segmental levels and may ascend the spinal cord via mul-tiple pathways. The general consensus is that the dorsal or posterior columnspinal pathways [21–24] primarily mediate the SEPs. Other pathways, such asthe dorsal spinocerebellar tracts [25, 26] and the anterolateral columns [27, 28],may contribute to the early SEP responses that are used for monitoring pur-poses. Despite the fact that SEPs are primarily mediated by the dorsal columnsand therefore are a means of directly assessing only sensory and not motorpathway function, they have proven to be extremely useful as a clinical tool fordetecting changes in spinal cord motor function, particularly when thesechanges result from mechanical insults.

It is important to realize that mixed nerves receive sensory and motor fibersfrom multiple nerve roots. Therefore, when mixed nerves are stimulated, the



electrophysiological responses that result from the stimulation (known as SEPs)are mediated by more than one nerve root prior to being mediated by the spinalcord. It is not unreasonable to expect that SEP changes should occur when thefunction of one of the contributing nerve roots becomes abnormal. However,the usefulness of SEPs for assessing spinal root function in patients diagnosedas having cervical spondylosis [29–31] and lumbar root lesions [32, 33] hasbeen limited. In addition, when used as a neurophysiological monitoring toolduring pedicle screw placements, they appear to be totally insensitive tochanges in nerve root function [34] (Figs. 11.1 and 11.2), largely because sev-eral nerve roots typically contribute to the composition of a peripheral nerve.For example, the posterior tibial nerve receives contributions from the L4, L5,S1, S2, and S3 nerve roots. As a result, a monoradicular functional abnormalitymay not be apparent when mixed-nerve evoked potentials are used to evaluatea patient because abnormal nerve root function may be masked by the normalactivity mediated via unaffected spinal nerve roots [35–37]. Therefore, mixed-nerve SEPs may be insensitive to irritation or injury to a single nerve root. Forthis reason, they should not be used to monitor spinal nerve root function,since other techniques are much better suited for this purpose. On the otherhand, since SEPs were developed and continue to be used as a technique forassessing spinal cord function, they might be useful during pedicle screw place-ments if spinal cord rather than nerve root function is placed at risk. However,since pedicle screws are usually placed at levels caudal to the conus medullaris(i.e., L2–S1), screw placement would not place spinal cord function at risk,and, indeed, there have been no published reports of the loss of spinal cordfunction during such procedures. Therefore, unless there is reason to believethat spinal cord function is at risk, there appears to be no basis for the use ofSEPs as a monitoring tool during pedicle screw procedures.

FIGURE 11.1 False-negative posterior tibial nerve SEP responses from a patient who sufferedintraoperative compression of the right L5 nerve root. The intraoperative responses wererepeatable and demonstrated no significant changes throughout the surgical procedure. Reprintedfrom [34].



2.1.2 Dermatomal Somatosensory Evoked Potentials (DSEPs)

A dermatome is defined as a body surface area that receives its cutaneous sen-sory innervation from a single spinal nerve root. It has been demonstrated thatDSEPs arise from stimulation of receptors in the skin rather than from subcu-taneous digital nerves [38]. As a result, they are normally elicited using someform of surface electrodes and are probably mediated via the same pathways asmixed-nerve SEPs.

The first reported use of dermatomal or segmental SEPs (as they were ini-tially named) was by European investigators [39]. Since these first studies, theyhave been used to assess children with myelomeningocele [40], to evaluatepatients with spinal cord injuries [41], as a monitoring tool during spinalsurgery to determine the adequacy of spinal nerve root decompression [42–44],and to detect nerve root functional impairment during pedicle screw placement[34, 45]. DSEPs are acquired using the same stimulation and recording tech-niques and equipment that are used to acquire mixed-nerve SEPs. Unlike SEPs,however, the only DSEP responses that are clinically useful are recorded from

FIGURE 11.2 CT scan of the patient whose SEP responses are shown in Fig. 11.1. The pediclescrew has entered the spinal canal and is in a position where the right-sided L5 spinal nerve root(left in the photo) was found on surgical inspection to be significantly compromised. Reprintedfrom [34].



the scalp, because it is normally very difficult to record either peripheral orsubcortical DSEP responses. This may be a function of the relative number of affer-ent nerve fibers that mediate and contribute to DSEPs as compared to mixed-nerve SEP responses. As a result, like mixed-nerve cortical SEP responses, DSEPresponses can be very susceptible to the anesthetic drugs that are used duringsurgery [45]. In addition, it has been shown that the latency and amplitude ofdermatomal responses are a function of the stimulation intensity [46]. Therefore,for monitoring purposes, stimulation intensity should remain constant through-out a surgical procedure so that one does not attribute response changes to sur-gical events.

DSEP responses, at least ideally, are considered to be nerve root–specific.However, this may not always be the case. Dermatomes tend to overlap, andtheir spatial distributions vary from person to person. Besides their suscepti-bility to typical anesthetic drugs, this is another minor shortcoming of this tech-nique. One of the two major limitations associated with the use of DSEPs is that,because of their small amplitude, they can only be acquired using an averagingtechnique; hence, their acquisition, like that of SEPs, may require a few min-utes. During this period of time, functional changes can occur that may goundetected until another average is acquired. At that point in time, nerve rootdamage may have occurred and the associated functional changes may be irre-versible. For pedicle screw placement, the second major limitation of the DSEPtechnique is that changes in dermatomal responses will only occur if a pediclescrew actually makes contact with a nerve root (Fig. 11.3). Misplaced screwsthat do not make contact with a nerve root may still represent a potential sourceof nerve root irritation or damage and will go undetected with the dermatomaltechnique.

FIGURE 11.3 Intraoperative responses obtained from a patient in which the right-sided L4 DSEPresponses increased in latency and then disappeared during screw insertion. The surgeon was noti-fied of the response changes and immediately removed the right L4 pedicle screw. The screw wasredirected and the responses returned to normal. The patient experienced no postoperative deficitsrelated to screw placement. Reprinted from [34].



2.1.3 Anesthetic Management for Sensory Techniques

Although the monitoring of SEPs has clearly been beneficial during many sur-gical procedures, the anesthesia used to facilitate these procedures produceseffects that alter the evoked potentials. These effects are well documented[47–50]. They are most prominent on the cortically generated responses andless so on the subcortical and peripheral responses. They are generally doserelated, and their effects on cortical SEPs tend to parallel their effects on EEG.Most of the commonly used anesthetic drugs produce dose-related SEP changesthat include amplitude decreases and latency increases. The relative degree ofchange differs between anesthetic agents. The drug dosage that causes a 50%decrease of cortical SEP amplitude correlates with the lipid solubility of theagent and therefore its anesthetic potency [48, 49]. Therefore, when anesthetictechniques are being considered, the effect of each anesthetic agent on specificmonitoring modalities must be considered.

Probably the most commonly used anesthetics are the halogenated inhala-tional agents (desflurane, enflurane, halothane, isoflurane, sevoflurane). Allthese agents produce a dose-related increase in latency and reduction in ampli-tude of the cortically recorded SEP responses. Several studies have demon-strated that halogenated agents differ in their potency of effect on cortical SEPs.Isoflurane has been reported to be the most potent, and enflurane and halothanethe least potent [49]. At steady state, the potency of sevoflurane and desfluraneappears to be similar to that of isoflurane. The effects are less on the subcorti-cal SEP responses recorded over cervical spine and are minimal on spinal res-ponses recorded epidurally or on peripherally recorded responses. If it isessential to monitor cortical SEPs, the use of halogenated inhalational agentsmay need to be restricted or eliminated entirely. However, if the recording ofsubcortical responses is adequate for monitoring purposes, halogenated agentsmay be acceptable anesthetic choices.

Nitrous oxide produces decreases in cortical SEP amplitude and increases incortical SEP latencies when used alone or in conjunction with halogenatedinhalational agents or opioid anesthetics. When compared to other inhalationalanesthetic agents at equipotent anesthetic concentrations, nitrous oxide pro-duces the most profound cortical SEP changes [50]. Like halogenated agents,the effects of nitrous oxide on subcortical and peripheral sensory responses areminimal. However, nitrous oxide has been reported to have a synergistic effecton cortical SEPs when used in conjunction with other inhalational agents.

Although the use of DSEPs represents an improvement over the use of SEPssince one is able to detect single nerve root functional changes, both SEP andDSEP cortical responses are sensitive to standard anesthetic management thatincludes the use of halogenated gases and nitrous oxide; the DSEPs are rela-tively more sensitive to these anesthetic agents than are mixed-nerve SEPS



because they are smaller in amplitude to begin with. This minor limitation canbe minimized by using anesthetic agents that are administered intravenously(total intravenous anesthesia–TIVA), but these anesthetic agents tend to bemore costly than the anesthetic gases.

A number of factors determine the choice of anesthetic agents when moni-toring is to be performed. These include (1) how anesthetic agents may interactwith a patient’s pathophysiology, (2) surgical requirements (i.e., performance ofa stagnara wake-up test, awake during a carotid endarterectomy procedure), and(3) the specific monitoring modalities to be used.

In general, anesthetic agents produce an alteration in the evoked responsesconsistent with their clinical effects on the CNS. Several important generaliza-tions can be made regarding the effects of anesthetic agents on SEPs. First, mosttend to decrease neural conduction and synaptic transmission. As a result, theytend to decrease the amplitude and increase the latency of SEPs. Second, theeffects of anesthetics on SEPs appear to be most prominent in regions wheresynaptic transmission is prominent. Therefore, their effects are most pro-nounced on cortically generated peaks and least effective on brainstem, spinalcord, and peripheral responses. Third, anesthetic effects appear to be doserelated, although many agents have a disproportionate effect at low dosages inthe range where major clinical anesthetic effects are occurring. Fourth, just aspatients react differently to the same dose of an anesthetic drug, so also theirSEPs are affected differently. Finally, during periods when neurological func-tion is acutely at risk, it is important to maintain a steady state of anesthesia.Taking into consideration all these factors, an anesthetic regimen can usuallybe chosen that will permit effective monitoring.

2.2 MOTOR PATHWAY ASSESSMENT TECHNIQUES

Myotomes are the motor complement to dermatomes, and myotomal distribu-tions are also quite variable between individuals. Whereas a myotome is a groupof muscles that receive their motor innervation from a specific spinal nerveroot, most muscles receive efferent innervation from several spinal nerve rootlevels. The amount and type of innervation to specific muscle groups will varyfrom person to person.

Myotomal activity can be spontaneously elicited by mechanical stimulationor triggered by electrical stimulation. Typically, the myotomal activity fromseveral muscle groups is monitored at any given time, and the activity isrecorded using either surface or subdermal needle electrodes placed over or intothe various muscle groups. The selection of the muscle groups to monitor ismade on the basis of which spinal nerve roots are at risk for irritation or injury.Muscles typically receive their innervation from several spinal levels, although



one spinal level generally predominates in terms of the amount of innervationit provides to any given muscle group. Activity can be recorded from musclesinnervated by the cervical, thoracic, lumbar, and sacral spinal nerve roots. Inaddition to paraspinal muscles, the muscles commonly used for these record-ings and their innervation appear in Table 11.1.

2.2.1 Spontaneous Myogenic Activity

The responses that are elicited when nerve roots are mechanically or electri-cally stimulated are summed responses from many muscle fibers known ascompound muscle action potentials (CMAPs). They can be recorded usingpairs of surface or needle electrodes that are placed over or into the belly of amuscle.

Recordings should be made continuously throughout a surgical procedure.Assuming that excessive amounts of muscle relaxants have not been adminis-tered to a patient during surgery and that muscles are adequately unrelaxed,spontaneous activity will be elicited when mechanical activation results innerve root irritation or injury. This spontaneous activity, suggestive of nerveroot irritation, can be recorded when train-of-four testing of target muscles (i.e.,muscle groups innervated by the nerve roots at risk) produces only one CMAP.The activity will typically be elicited from one or more muscle groups, depend-ing on the activated nerve root, the muscle groups being monitored, and theplacement of the recording electrodes on these muscle groups.

The EMG activity from each electrode pair is recorded using differentialamplification and is filtered using a wide bandpass filter (30 Hz–3 kHz).

TABLE 11.1 Innervation to Various Muscle Groups

Innervation levels Muscles

Cervical C2, C3, C4 Trapezius, SternocleidomastoidC5, C6 Biceps, DeltoidC6, C7 Flexor Carpi RadialisC8, T1 Abductor Pollicis Brevis,

Abductor Digit Minimi

Thoracic T5, T6 Upper Rectus AbdominisT7, T8 Middle Rectus AbdominisT9, T10, T11 Lower Rectus AbdominisT12 Inferior Rectus Abdominis

Lumbosacral L2, L3, L4 Vastus MedialisL4, L5, S1 Tibialis AnteriorL5, S1 Peroneus Longus

Sacral S1, S2 GastrocnemiusS2, S3, S4 External Anal Sphincter



When spontaneous myogenic activity is recorded to detect mechanical nerveroot irritation, the data acquisition system should be set to operate in the freerun mode. In this mode, the sweep time is typically 1 s and any elicited activ-ity can easily be visualized and evaluated. Typically, several channels of myo-genic activity should be monitored simultaneously, depending on the numberof channels available, but six or more should be monitored.

When interpreting spontaneous activity, there are several factors to take intoconsideration. First of all, normal nerve roots and irritated or regeneratingnerves in continuity react differently to mechanical forces. When mechanicalforces are statically or rapidly applied to normal nerve roots, they induce nonerve root activity or trains of impulses of short duration [51]. When the sameforces are applied to irritated or regenerating nerves, they induce long periodsof repetitive impulses. Minimal acute compression of normal dorsal root gan-glion also induces prolonged repetitive firing of nerve roots. When interpretingintraoperative motor nerve root activity, it is important to understand thepathophysiological mechanisms of nerve root injury and to understand theresponse of normal and pathological nerve to not only different types ofmechanical force but also to electrical stimulation.

Normally, the recordings of spontaneous activity will demonstrate the lackof activity. However, when preexisting nerve root irritation has been present,the recordings will often consist of low-amplitude periodic firing patterns.Mechanically elicited activity consists of either short bursts of activity that canlast a fraction of a second or long trains of activity that can last up to severalminutes (Fig. 11.4). The short aperiodic bursts of activity are common. Atten-tion should be paid to these, but they are normally not cause for alarm and arerarely indicative of a neural insult. The long trains are more serious, may beindicative of neural injury, and are causes for alarm. The short bursts are asso-ciated with direct nerve trauma such as tugging and displacement, irrigation,electrocautery, metal-to-metal contact, or application of soaked pledgets. Trainactivity is commonly related to sustained traction and compression. The moresustained the activity, the greater the likelihood of nerve root damage. Whentrain activity occurs, the surgeon must be notified so that corrective measurescan immediately be taken.

2.2.2 Triggered Myogenic Activity

As mentioned earlier, triggered myogenic activity can be elicited in severalways: through direct nerve root stimulation [12], indirect nerve root stimula-tion by means of stimulation of spinal instrumentation [9, 13, 15, 46, 52], directspinal cord stimulation (myogenic motor evoked potentials) [53, 54], and trans-cranial motor evoked potentials elicited by either electrical or magnetic trans-cranial stimulation [55, 56].



2.2.2.1 Transcranial and Spinal Stimulation

Both spinal cord and transcranial stimulation are typically used to elicit myo-genic responses from lower-extremity muscle groups in order to assess spinalcord motor function. They can also be used to assess individual nerve root func-tion during pedicle screw placements. However, they typically are not used inthis fashion, for several reasons. First, these techniques are more complex thanother techniques that are currently available; they require special equipment,electrode placement skills, anesthetic management, and/or consent for theirimplementation. Second, functional status can only be determined when stim-ulation occurs, and not continuously. Third, although myogenic responses can

FIGURE 11.4 Spontaneous myogenic activity elicited from the left tibialis anterior muscle as aresult of mechanical irritation of the left L5 nerve root. Short bursts of such activity are sometimesobserved with manipulation of nerve roots that are not irritated or injured. Such activity is consid-ered insignificant and rarely results in postoperative sequelae. Sustained activity (more than asecond) is attributed to the manipulation of irritated nerve roots or to nerve root injury. Such activ-ity is considered significant and should be avoided to minimize the chances of postoperativedeficits. Reprinted from [52].



generally be elicited from some designated target muscle groups such as thetibialis anterior muscles, the threshold stimulation intensities needed to elicitmyogenic responses from other designated target muscles vary from muscle tomuscle. These thresholds can vary during a procedure, and these changes maybe unrelated to surgical causes. Therefore, their reliability in determining whena surgical event has caused a functional change is in question. Finally, the tech-niques can only detect when functional changes have already occurred; they arenot able to detect potential causes of functional changes. As a result, investiga-tors have turned to other techniques for monitoring nerve root function duringpedicle screw placements. These techniques include direct nerve root stimula-tion and indirect nerve root stimulation by means of stimulation of spinalinstrumentation.

2.2.2.2 Direct Nerve Root Stimulation

Direct nerve root stimulation is sometimes used to determine the stimula-tion thresholds of nerve roots placed at risk during screw placement. Ideally,this technique should be used in conjunction with indirect nerve root stimu-lation when stimulation thresholds are in question, either as a result of chronicnerve root compression (particularly when a radiculopathy is present) [57, 58]or when disease processes are present, such as diabetes, that may effect nerveroot function. It is generally assumed that when nerve roots are indirectly stim-ulated via the spinal instrumentation, the nerve roots that are being excited arehealthy and function normally. Maguire et al. [9] reported that the constantcurrent stimulation threshold for eliciting responses from normal nerve rootsranged from 0.2 to 5.7 mA, with an average stimulation intensity of 2.2 mA.Calancie et al. [13] reported that constant current stimulation thresholds fornerve roots ranged from 1.2 to 3.8 mA with an average of 2.1 mA. However,investigators have reported that chronically compressed nerve roots have ele-vated stimulation thresholds [57, 58], and Holland et al. [58] reported thatstimulation thresholds greater than 20 mA may be necessary to elicit myo-genic responses from such nerve roots. These findings indicate that if test para-meters that have been developed from testing pedicle screw placements inpatients with normal nerve root function are used to test screw placementsinvolving chronically compressed nerve roots, false-negative findings canresult.

As indicated earlier, elevated stimulation thresholds may also occur inpatients with metabolic disorders such as diabetes. However, to my knowledge,no reports have appeared in the literature to support this supposition. Our ownexperience with such patients is limited, but some of the diabetic patients wehave tested have had only moderately elevated stimulation thresholds. Ratherthan having thresholds of 2 mA or less, the diabetic patients have been found



to have thresholds of 4–5 mA—still in the normal range reported by otherinvestigators [9].

One way to avoid false-negative findings is to directly stimulate each nerveroot at risk to ensure that it is functioning normally before testing the place-ment of each pedicle screw. Although this may be a reasonable step if decom-pressions are being done, routine laminotomies to explore each nerve root aretime-consuming and can be associated with undue risk. Therefore, most sur-geons may prefer not to use direct stimulation of nerve roots in conjunctionwith indirect nerve root stimulation techniques. However, in patients exhibit-ing signs of nerve root malfunction as a result of either compression or diseaseprocesses, it is strongly suggested that direct nerve root testing be performed toestablish stimulation thresholds when indirect nerve root stimulation tech-niques are being used.

2.2.2.3 Indirect Nerve Root Stimulation Techniques

Indirect nerve root stimulation is performed by electrically stimulatingbone or hardware in order to elicit nerve root responses. Some surgeons favorsuch testing during every aspect of pedicle screw placement. They test theprobe used to make the initial hole into the pedicle for marker placement, themarkers, the taps used to make the holes for the pedicle screws, the pediclescrew holes, and the pedicle screws themselves. Other surgeons may prefer totest only the screw placements. The assessment criteria are similar in all cases.

Several articles have reported on the efficacy of these techniques [9, 13–16,46, 52, 57–64]. The published stimulation parameters that have been usedhave varied. These studies have used either constant current or constant volt-age stimulation to assess placements. Although similar, these two forms ofstimulation are not equivalent. The flow of electrons, also known as currentflow, is what actually causes a nerve or nerve root to depolarize. Voltage is onlythe driving force that causes the electrons to flow through the resistance orimpedance of biological tissue. When testing pedicle screw placements, tissueimpedance includes that of pedicle and vertebral body bone in addition to the impe-dance of muscle, vascular tissue, and blood. Although the latter impedancesprobably remain relatively constant between individuals, bone density andtherefore bone impedance is known to vary between individuals as a result ofosteoporosis and other factors. Therefore, it takes more or less voltage to causethe same current to flow in various individuals. Therefore, it would beexpected that the results of using constant voltage for testing pedicle screwplacements would be more variable than constant current stimulation. Severalinvestigators have already reported this to be the case [9, 61], and our findingsare in agreement (Fig. 11.5). Constant current stimulation appears to be supe-rior to constant voltage stimulation for assessing pedicle screw placements.



Various stimulation parameters and techniques have been used to electri-cally assess pedicle screw placements. A probe of some type such as a nasopha-ryngeal electrode functions as the cathode and is placed within the pediclescrew holes and/or on hardware, and a needle electrode is typically placed inmuscle near the surgical site (Fig. 11.6). It is used as the anode and provides a

FIGURE 11.5 A graph of the constant voltage versus constant current stimulation intensitiesrequired to elicit myogenic responses when the same pedicle screw was stimulated. Nerve root exci-tation is always a function of current flow. Although a linear relationship exists between these twostimulation techniques, constant voltage stimulation appears more variable than constant currentstimulation. This variability may be a function of the resistance of the pedicle bone.

FIGURE 11.6 The stimulation technique used to assess pedicle screw placements. The same tech-nique can be used to test markers, taps, and pedicle holes. In this case, the pedicle screw has brokenthrough the wall of the pedicle and is situated very close to an emerging nerve root. As a result, elec-trical current, following the path of least resistance through the pedicle screw and the breach in thepedicle wall, is expected to excite the nerve root. Excitation typically occurs at very low stimula-tion intensities and results in triggered myogenic responses from muscles innervated by the nerveroot. Reprinted from [52].



FIGURE 11.7 Radiographic data (A) and pedicle screw stimulation data (B, C) acquired duringthe same surgical procedure. (A) The lateral radiograph shows the pedicle screws that were placedinto the L4 and L5 vertebrae. Although the radiograph suggests adequate screw placement at boththese levels, it cannot indicate any medial screw displacement. (B, C) Triggered myogenicresponses were elicited by stimulation of the left L4 (B) and left L5 (C) pedicle screws. The stim-ulation intensity was initially 0.0 mA and was gradually increased until triggered responses wereevident. The threshold stimulation intensity (current level at which responses were first elicited)for the left L4 screw (B) was 32.6 mA, which was suggestive of adequate screw placement. Thethreshold stimulation intensity for the left L5 screw (C) was 4.3 mA, which was suggestive of apotentially harmful screw placement. The placement of the left L5 screw was visually inspectedand confirmed to be positioned in the spinal canal. It was removed. Reprinted from [52].



return path for the stimulation current. Rates of pulsatile stimulation haveranged from 1 to 5 Hz with pulse durations of 50–300 ms [61]. Typically, whentesting, the intensity of the stimulation is gradually increased from 0 mA untila current threshold is reached at which a reliable and repeatable EMG responseis elicited from at least one of the monitored muscle groups or a predeterminedmaximum stimulus intensity is reached. For safety reasons, we generally use50 mA as a maximum stimulation intensity. If EMG responses are elicited at astimulus intensity that is lower than a predetermined “warning threshold,” i.e.,the stimulus intensity that is used to warn of a possible breach of the pediclewall, the surgeon is advised to examine the hole or hardware placement. Insuch instances, radiographs may falsely suggest adequate screw placements(Fig. 11.7). These “warning thresholds” have varied between groups of inves-tigators. Some have used stimulus intensities of 10 mA or higher, whereasothers have used intensities as low as 6 mA [61].




2.3 ANESTHETIC MANAGEMENT

FOR MOTOR TECHNIQUES

In order to provide an optimal surgical field, the anesthesiologist must rendera patient unconscious and free from pain and must also control muscle tone.The degree of muscle relaxation is the only anesthetic factor of concern whenmyogenic activity is used for monitoring purposes. One way to suppress muscletone is to suppress it at its origin, within the cerebral cortex, with deep anes-thesia [65]. Although nitrous oxide does not produce muscle relaxation, theadministration of the halogenated agents such as halothane, enflurane, andisoflurane does have a dose-related effect. However, because of cardiovasculardepression, these agents cannot be used by themselves to produce the amountof relaxation necessary for abdominal surgery. A second means of diminishingmuscle tone is to block the signals from the brain to the muscles as they traverse




the spinal canal by using either spinal or epidural anesthesia. A third means ofdoing so is to use neuromuscular blocking agents that interfere with the trans-mission of signals from motor nerves to muscle fibers. In order to avoid majorarterial hypotension, neuromuscular blockade is achieved by the use of a neu-romuscular blocking agent in conjunction with a volatile halogenated agent. Inthis way, the anesthetic is used to produce only unconsciousness and analgesiaand can be administered at low safe concentrations.

When monitoring nerve root function using the spontaneous or triggeredmyogenic activity from specific muscle groups, it is imperative that thesemuscle groups be sensitive to changes in nerve root function resulting fromtraction or compression of the roots. The level of muscle relaxation signifi-cantly affects myogenic responses. The greater the degree of muscle relaxationfor the muscle groups of interest, the less likely they will be to respond tochanges in nerve root function. As a result, it would be ideal if no muscle relax-ation were used to interfere with elicited activity. To be absolutely sure thatrelaxation levels play no part in determining response thresholds, some neuro-physiologists insist on patients being totally unrelaxed when testing. However,in many clinical settings, this level of relaxation may be difficult if not impos-sible to achieve, particularly if surgeons feel that it compromises their ability toadequately perform surgery.

An effective means of assessing the degree of muscle relaxation is to use atrain-of-four technique, which consists of electrically stimulating a peripheralnerve four times and recording the four CMAPs (T1, T2, T3, and T4) that resultfrom target muscle groups. For the hands, the ulnar nerve could be stimulatedat the wrist with CMAPs recorded from the adductor digiti minimi muscle. Forthe legs, the peroneal nerve could be stimulated at the fibular head and CMAPscould be recorded from the tibialis anterior muscle. Typically, 2 Hz, 0.2 mspulses of supramaximal stimulation intensity are used to elicit the CMAPs. TheT4 CMAP disappears with a 75% blockade, the T3 with 80%, T2 with 90%, andT1 with 100% [66, 67].

2.4 FACTORS THAT CAN CONTRIBUTE

TO FALSE-NEGATIVE FINDINGS

When pedicle screws have breached pedicle walls, these events should bedetectable when using electrical stimulation for test purposes. When this formof testing fails to detect these events, false-negative findings in the form of nerveroot irritation or damage can result. Several factors, both technical and physi-ological, can contribute to such findings. The following is a discussion of thesefactors.



2.4.1 Degree of Muscle Relaxation

Probably the most important factor when testing during the placement of pedi-cle screws is the degree of muscle relaxation, because it can significantly influ-ence the stimulation thresholds at which responses are elicited. Therefore, anaccurate assessment of muscle relaxation is essential. Train-of-four testing is acommon way for anesthesiologists to make these assessments. Although thistesting technique appears to be a reasonable way to make these assessments,testing should be done by the person providing the monitoring rather than bythe anesthesiologist, for several reasons. First, the anesthesiologist typicallydoes a train-of-four assessment using a small portable battery-driven device.These devices may not always work properly and should not be relied upon.Second, the anesthesiologist’s assessment of train-of-four test results is a sub-jective one based on visible twitches from muscle groups that the anesthesiol-ogist has access to—either hand or facial muscles. It is unlikely that theresponses from these muscle groups will be the same as those from the leg mus-cles from which responses are elicited when pedicle screw testing is performed,because these muscle groups react differently to the relaxant levels. Finally, itis appropriate that the person providing the monitoring be responsible for guar-anteeing that the test results are as accurate as possible by doing his or her owntrain-of-four testing of leg musculature.

The issue of what are adequate relaxant levels for accurately assessingthreshold stimulation intensities remains controversial. Clearly, no sponta-neous or triggered myogenic activity will be present with 100% blockade. Onthe other hand, it has been reported that it is not necessary to have the absenceof any blockade to effectively monitor spontaneous and triggered myogenicactivity. We have observed that spontaneous activity can be elicited with onetwitch present during train-of-four testing, or up to 90% neuromuscular block-ade. However, when using indirect stimulation during pedicle screw placement,the assessment criteria make a determination of relaxant levels much more crit-ical. It cannot be overstated how important it is to have the patient adequatelyunrelaxed when testing. If a patient is too relaxed when testing is performed,the stimulation thresholds for eliciting responses will be artificially elevatedand may lead to false-negative findings. One example of this from personalexperience occurred when a patient had only one large twitch during train-of-four testing and pedicle screw testing was performed. The stimulation thresh-old was found to be 50 mA. Further screw testing was delayed until a smallfourth twitch became evident during train-of-four testing. Stimulation of thesame screw then resulted in a threshold of 12 mA! Clearly, the relaxant levelassociated with the presence of only one twitch during train-of-four testing maybe adequate for eliciting spontaneous activity, but it is not adequate for testingduring screw placement. It has been reported that the minimal criterion for



making such assessments is the presence of a fourth twitch from a target muscle[52, 68]. It has also been proposed that a postinduction–preinduction CMAPamplitude ratio from a hand muscle that is greater than 0.8 is a better measurefor determining adequacy of relaxation [70]. Our own service is currently usingan amplitude ratio of the fourth to the first twitch to determine adequacy ofrelaxation criteria for assessing screw placements. Based on surgical findingswhen visualizing screw placements after experiencing stimulation thresholdsbelow “warning thresholds,” we now feel that the value of this ratio must be atleast 0.1 (Fig. 11.8).

The direct electrical stimulation of nerve roots is one means of determiningif the level of muscle relaxation is adequate for using myotomal responses to

FIGURE 11.8 Train-of-four test data. The right side of the figure indicates the four myogenicresponses elicited from the left tibialis anterior muscle as a result of stimulation of the left peronealnerve at the head of the fibula. Four 0.3 ms pulses with an intensity of 40 mA were presented at arate of 2 Hz. On the left side of the figure, the myogenic response amplitudes resulting from the firstand the fourth stimuli were measured and the amplitude ratio of the fourth over the first twitch wascalculated. A minimum ratio of 0.1, based on previous findings [69], was used for testing purposes.



assess nerve root function. If myogenic responses cannot be elicited using aconstant current stimulation level of 2–4 mA, it is likely that the muscle relax-ant level is too high to effectively monitor nerve root function using myogenictechniques. Considering the importance of proper relaxation, further studiesneed to be done to correlate the results of direct nerve root stimulation withnoninvasive twitch monitoring.

2.4.2 Current Shunting

It was pointed out earlier that excitation of a nerve root only occurs when a por-tion of the current being applied in a pedicle hole or to pedicle hardware is ade-quate to excite and depolarize the nerve root. The stimulation current that isused to test pedicle screw placements can exit the screw through several dif-ferent pathways and will seek the pathways of least resistance as the currentreturns to the anodal electrode. When a pedicle screw breaches a pedicle wall,it provides a pathway for current to exit. The larger the breach, the lower theresistance to current flow, and the greater the amount of current that will flowthrough the breach. If a nerve root is located close to the breach, excitation ofthe nerve root will occur. However, if fluid is allowed to accumulate at the sur-gical site so that the fluid makes contact with the stud of a pedicle screw, thatfluid will provide another low-resistance pathway for current to flow away fromthe screw. Less current will exit through the pedicle wall, and the amount ofcurrent needed to flow into the pedicle screw and cause depolarization of thenerve root will increase. As a result, we found that stimulation intensitiesneeded to elicit myogenic responses generally increased between 12 and 20 mA[70] (Fig. 11.9). It is interesting that despite the low resistance of the fluid, cur-rent is not completely but only partially shunted away from the pedicle screw.Therefore, if shunting is present, it appears that it can mask the presence of abreached pedicle and result in false-negative findings when stimulation inten-sities are less than 30 mA. However, at stimulation intensities greater than this,such an occurrence seems unlikely.

2.4.3 Physiologic Factors

The physiologic factors that can contribute to false-negative findings largelypertain to the health status of the stimulated nerve roots. The threshold crite-ria for all of the stimulation techniques that are used for testing purposes arebased on the assumption that the nerve roots that are being excited by the pedi-cle screw stimulation are healthy and function normally. These nerve roots,when directly stimulated, have excitation thresholds of about 2 mA. However,it has been reported that chronically compressed nerve roots have elevated



stimulation thresholds [57, 58]. For some of these nerve roots, thresholds mayeven exceed 20 mA [56]. Therefore, the use of the “warning threshold” fornormal nerve roots when testing chronically compressed nerve roots may alsocontribute to false-negative findings.

In the author’s experience, we have had two cases of chronic nerve rootcompression in which nerve root thresholds were determined as a result ofdirect nerve root stimulation and were found to be elevated. In the first case,the patient was diagnosed with spinal stenosis, and a right L5 nerve root thathad been chronically compressed had a stimulation threshold of 5.5 mA. Inthe second case, the patient presented with a left-sided drop foot of about1 month duration that occurred immediately after a previous back surgery.The placement of the left L5 screw was visually examined during surgery andwas found to be in contact with the left L5 nerve root. Direct stimulation ofthe left L5 nerve root just outside the foramen resulted in a stimulationthreshold of 13.7 mA.

Stimulation thresholds may also be elevated when testing patients with meta-bolic disorders such as diabetes. Our experience with such patients is limitedwith regard to directly stimulating nerve roots and acquiring thresholds. Thosewe have tested have either exhibited normal thresholds or thresholds that havebeen only slightly elevated (thresholds of 4–6 mA).

FIGURE 11.9 Data showing the effects of current shunting. Twenty-one pedicle screws werestimulated, and the threshold intensities for eliciting myogenic responses were determined withminimal fluid in the surgical field (“dry” testing) and with fluid in contact with the pedicle screws(“wet” testing). The consistent increase in stimulus intensities needed to elicit myogenic responseswhen “wet” testing indicates the effects of current shunting.



2.5 IMPEDANCE TESTING

An alternative approach to pedicle screw stimulation is to use the electricalimpedance of biological tissues as a means of assessing pedicle screw place-ments. Using a porcine model, Myers et al. [71] reported on a method forassessing pedicle wall thickness using impedance techniques. They were ableto determine that the impedance of intact vertebral bone was about 400 Ω(400 ± 156 Ω) when a probe was first inserted into a pedicle and decreased asthe depth of insertion increased. For an intact pedicle, the vertebral impedancedecreased to 100 ± 22 Ω at maximum probe penetration. The accuracy of thetechnique was determined using postmortem anatomical confirmation of thepedicle probe placement and regression analysis of the impedance data. Basedon this model, it was determined that impedance values below 58 Ω were asso-ciated with a 100% likelihood of a breach in the pedicle wall. These data weregathered from probing pedicle holes and measuring the impedance of the walls.Although very promising, the authors recognized that the technique’s utilityneeded to be demonstrated for implanted pedicle screws. Thus far, this utilityhas not been demonstrated. When testing implanted pedicle screws, the factorsthat contribute to the measured impedance become much more complex thansimply measuring the tissue impedance at various points on the pedicle wall(Fig. 11.10). Other investigators [59] besides ourselves have compared theimpedance measurements taken from pedicle screws to the results obtained viaelectrical stimulation. Our findings are in agreement that the impedance read-ings were very variable, with no correlation to electrical stimulation data or find-ings from visual observation (Fig. 11.11). At the present time, impedancemeasurements do not appear useful for assessing pedicle screw placements.

FIGURE 11.10 The impedance that is measured when a pedicle screw is in place is a complexmeasurement consisting of the combined impedance of many tissue elements.



Further refinements in the technique may be necessary to make this techniqueuseful.

3 PERSONAL EXPERIENCE

For many years, mixed-nerve SEPs have traditionally been used to monitorspinal cord function during spinal instrumentation procedures in order to min-imize the probability of postoperative neurological deficits [17–20, 24, 25]. Inthe past 10–15 years, intrapedicular fixation of the thoracolumbar and lum-bosacral spine by means of pedicle screw instrumentation has become increas-ingly popular. With increased use of pedicle screw instrumentation camevarying degrees of neurological impairment. However, when the implementa-tion of pedicle screws was increasing, the only forms of neurophysiologicalintraoperative monitoring that were available to avoid postoperative neurolog-ical deficits were mixed-nerve SEPs. One of the patients that was monitored inthis fashion using SEPs elicited by posterior tibial nerve stimulation had com-plaints of paresthesia and numbness of the right great toe immediately aftersurgery. The scope and intensity of these symptoms increased, and the patientwas clinically found to also have increasing weakness of the dorsiflexors andextensor hallucis longus muscle on the right side. A computed tomography(CT) scan was subsequently obtained that provided evidence of pedicular screwirritation of the nerve root (Fig. 11.2). Subsequent surgery revealed that theright L5 pedicular screw was located medial to the pedicle and juxtaposed tothe right L5 nerve root. Review of the intraoperative monitoring tracingsrevealed no significant changes in the monitored responses throughout the sur-gical procedure. In addition, tracings acquired during postoperative testing

FIGURE 11.11 Impedance versus threshold stimulation intensity data. There was no correlationbetween the impedance readings taken from the top of the pedicle screws and the threshold currentintensities needed to elicit myogenic responses or findings from visual inspection of screw placements.



were comparable to those obtained intraoperatively (Fig. 11.1). SEPs are typi-cally mediated by several spinal nerve roots. It was surmised that the reason themonitored SEPs did not demonstrate any changes was that the functional com-promise of the single L5 nerve root was masked by the normal volleys mediatedby unaffected nerve roots. On the basis of this one case, it was determined thatmixed-nerve SEPs might be an inappropriate tool for monitoring procedures inwhich nerve root rather than spinal cord function is at risk. The use of SEPs formonitoring purposes was abandoned, and other methodologies were sought formonitoring during pedicle screw procedures. As a result, DSEPs, which previ-ous studies had already indicated were an effective means of assessing singlenerve root function [35–44], were used to monitor pedicle screw procedures[34, 45].

Subsequently, the results of our experience using DSEPs as a monitoringtool during surgical intrapedicular fixation procedures were published [35].They indicated that the loss of DSEP responses appeared to be a sensitive indi-cator of mechanical root compression (Fig. 11.3), whereas DSEP responseswere rarely found to change to any significant degree during root decompres-sion or even several days post surgery. However, because of the major short-comings associated with DSEPs (i.e., the time-consuming need for averaging toacquire responses and the insensitivity to potential sources of nerve root irrita-tion or damage), their use was later abandoned in favor of monitoring sponta-neous myogenic activity in conjunction with indirect nerve root stimulationresponses. Monitoring using a combination of both these techniques appears tohave adequately addressed all of the DSEP shortcomings.

Although the monitoring of spontaneous myogenic activity is used to safe-guard nerve roots during pedicle screw placement, the actual probability ofnerve root irritation or injury during these placements, although finite [35],appears to be very small. Having kept data from over 1000 surgical proceduresthat have involved the placement of over 5000 pedicle screws, we have neverobserved any sustained (longer than 2 s) spontaneous activity that was associ-ated with the tapping of screw holes or the placement of markers or screws. Sus-tained spontaneous activity has been observed in less than 4% of the patientsthat have been monitored, and this activity has always been associated withmechanical nerve root irritation during traction or decompression. Others havereported similar findings [14].

Based on the data that were acquired from 662 patients using a “warningthreshold” of 10 mA (using a stimulus duration of 0.2 ms), we have publishedour findings [52] on the correlation between responses elicited at or belowwarning threshold, the surgical findings, and the actions surgeons took basedon visual inspection of the screw placements (Fig. 11.12). When EMGresponses were elicited at or below 5 mA, screws were almost always removedand might be redirected. If responses were elicited at intensities at or greater



than 8 mA, screws were generally left in place. Between 5 and 8 mA, screwswere equally likely to be removed or left in place. Therefore, despite the fact thatstimulation thresholds less than 5 mA generally resulted in screw removal,screw removal also occurred at stimulation intensities up to and including the“warning threshold” of 10 mA. These findings support the findings of others[9, 10, 13–15, 46, 61, 62, 68], which indicate a close correlation between theintensity of screw stimulation needed to elicit myogenic responses and the riskfor neurological injury associated with the screw placements.

When electrical stimulation is used to assess hardware placement or theintegrity of a pedicle hole, the stimulation current can take many pathways asit returns to the anodal needle electrode, but it will follow those pathways thatprovide the least resistance (Fig. 11.13). When hardware or pedicle hole stim-ulation is associated with low-threshold stimulation intensities, the results sug-gest that a path of least resistance is located near a nerve root, but one cannottell whether the pathway is through a cracked pedicle, a thin wall of osteo-porotic bone, or an exposed pedicle screw. Responses elicited at stimulationintensities below the “warning threshold” could result from current flowthrough any of these pathways. However, there does appear to be a relationshipbetween threshold stimulation intensities and the exposure of a pedicle screw;i.e., cracked pedicles or a minimally exposed screw tends to be associated withstimulation thresholds greater than 7 mA, whereas exposed screws near a nerveroot tend to have thresholds less than 5 mA. However, not all low-threshold

FIGURE 11.12 Data from 662 patients whose screws were found to have a “warning thresh-old” less than or equal to 10 mA. After visual inspection, those screws with thresholds less than5 mA were generally removed. Screws with thresholds between 5 and 8 mA were equally likelyto be removed or left in place. Screws with thresholds of 8 mA or greater were generally left inplace. However, some screws with thresholds as high as 10 mA were also removed. Reprintedfrom [52].



readings are associated with screw placements that represent threats of poten-tial neurological injuries. Testing of pedicle screws in two patients resulted ineach having a screw with a stimulation threshold less than 5 mA. After visualinspection, neither was removed because their placement did not appear to rep-resent a threat of potential neurological injury. Neither patient experienced anypostoperative pedicle screw–related neurological deficits.

Based on the author’s experience and the results of other investigators, screwplacements that are associated with stimulation thresholds greater than 10 mAare unlikely to represent a risk to neurological function if normal healthy nerveroots are involved and testing conditions are adequate. However, several fac-tors, both technical and physiologic, can contribute to false-negative findingswhen stimulation thresholds exceed “warning thresholds.” These includeexcessive muscle relaxation, current shunting as a result of excessive fluid in thesurgical site, and chronic nerve root compression. Examples of all three of thesefactors appear in the chapter text.

Since 1995, our service has monitored well over 1000 patients duringsurgery in which over 5000 pedicle screws were placed. For each patient, aphysical therapist and the attending physician routinely performed postopera-tive assessments. These practitioners were asked to inform the monitoring staffof any imaging or surgical evidence of misplaced hardware or any functionaldeficits that could be attributed to hardware placement. Based on their infor-mation, only one patient has experienced a postoperative neurological deficitdirectly attributable to a misplaced pedicle screw. In that patient, pedicle screwswere placed from L3 to L5. The patient had stimulation thresholds thatexceeded the “warning threshold” of 10 mA in all cases except for the left and

FIGURE 11.13 The stimulation current that is used to assess pedicle screw placements can takemany pathways as it returns to the anodal electrode that is placed in muscle tissue. The current willfollow those pathways that provide the least resistance.



right L3 screws, which had thresholds of 6.7 and 5.1 mA, respectively. The sur-geon elected to leave these screws in place. Immediately after the operation, thepatient experienced symptoms of low back pain and right leg pain. The patientwas brought back to surgery, and both L3 pedicle screws were removed andreplaced with sublaminar hooks at L3 and pedicle screws at S1 using TexasScottish Rite Hospital (TSRH) instrumentation and a crosslink. Following thisprocedure, the patient’s leg pain completely resolved. This is considered a goodexample of a true-positive finding. We have also had what we consider to be onefalse-negative finding, although the patient did not experience any postopera-tive neurological symptoms as a result of the screw placement. After operation,the patient reported unilateral back and leg pain. Postoperative CT scans werenot routinely performed for our patients, but in this case one was ordered andrevealed a screw that was positioned medial to the pedicle in the spinal canalon the asymptomatic side. Because of the location of the screw, it was removedless than 1 week after it had been placed and before it caused any postoperativenerve root irritation. Unfortunately, in this one case, the screw was removedwithout any repeated testing to confirm earlier monitoring findings. A retro-spective review of these findings indicated that the stimulation thresholds forthe four placed screws were 40–50 mA. Routine train-of-four testing of the legmusculature performed by the monitoring staff just before and after screwplacement indicated that the level of paralysis was adequate for accurate assess-ments because four full twitches could be elicited from the tibialis anteriormuscle. Although this patient did not experience any new postoperative deficitsas a result of screw placement, the electrical stimulation technique should havedetected the misplaced screw. Thus this result is considered a false-negativefinding. None of the factors that have been discussed earlier can explain theseresults. Therefore, it is possible that other factors that are not obvious to us mayalso contribute to false-negative findings.

4 CONCLUSIONS

The incidence of neurological complications associated with the placement ofpedicle screws has been reported as 2–10% [68, 72, 73]. Based on these esti-mates of incidence, we would then expect that for every 1000 patients in whichpedicle screws were placed, between 20 and 100 should have exhibited somenew postoperative neurological deficits directly attributable to screw place-ment. Our outcome data, which indicate that only 1 patient in our populationof over 1000 patients has thus far exhibited such symptoms (actually, the resultof a screw with a low test threshold that was left in place), clearly suggest thatour use of pedicle screw stimulation to monitor screw placements has playedan important role in minimizing the incidence of such deficits. The technique



appears to be very reliable for detecting breaches of the pedicle wall, even thosethat may pose no threat of causing neurological irritation or injury. It providesan easy, quick, and accurate means to assess pedicle screw placements and tosafeguard neurological function.

In the real world, it is also essential that monitoring be cost-effective. Thatis, the overall costs of monitoring should not exceed the costs associated withpatient care if monitoring is not provided. In most institutions at this time, thecost of monitoring for a typical instrumented fusion involving pedicle screwplacement with spontaneous and triggered myogenic techniques is generally$1000 or less. Therefore, the cost associated with monitoring 1000 procedureswould be $1 million. However, as indicated earlier, the minimal expected inci-dence of postoperative neurological deficits resulting from the placement ofpedicle screws is 2%, and it would involve at least 20 patients. Therefore, if theaverage medical costs to correct a patient’s postoperative outcome and to reha-bilitate that patient are more than $50,000, then the monitoring is cost-effective.It is very unlikely that $50,000 would cover all of the resultant medical costs. Thisdiscussion of cost-effectiveness does not even take into account the medical andlegal costs associated with each of these occurrences. Clearly, monitoring duringpedicle screw placement is cost-effective.

All the techniques that can be used to monitor during pedicle screw place-ments have some limitations. The combined use of spontaneous and triggeredmyogenic activity is the only technique that meets all the necessary criteria if itis to be widely and effectively used to assess pedicle screw placements and topreserve nerve root function.

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C H A P T E R 12

Surgery of BrainstemLesionsALBINO BRICOLO AND FRANCESCO SALA

Section of Neurosurgery, Department of Neurological Sciences and Vision,Verona University, Verona, Italy

1 Introduction2 Patient Selection and Rationale for Surgery3 General Principles of the Surgical Strategy

3.1 Midbrain3.2 Pons3.3 Medulla and Cervicomedullary Junction

4 Postoperative Care5 Neurophysiological Monitoring6 ConclusionReferences

ABSTRACT

During the decade of the brain, a more rational and constructive approach to the sur-gical management of neoplastic and vascular brainstem lesions has emerged. Theattitude held by many in the neurosurgical community who regard the brainstem as“untouchable” has been progressively counterbalanced by increasing evidence thatsurgical “violation” of the brainstem is safely feasible in certain subgroups ofpatients. Multiplanar MRI allows for an accurate distinction between differentgrowth patterns of brainstem mass lesions. MRI data, together with a refined neuro-logical evaluation, support the decision-making process in selecting those patientsamenable to surgical treatment and help in planning an optimal surgical strategy.Surgery of the brainstem, however, remains a challenging task that requires adetailed understanding of the microsurgical and functional correlative anatomy ofthe brainstem. In this chapter we will first revisit those aspects of functional neu-roanatomy relevant to modern neurosurgical approaches to the brainstem. Theanatomy of the brainstem is characterized by an extremely dense, although phylo-genetically ordered, concentration of functionally relevant structures such as cranialnerve nuclei, motor and sensory pathways, crossing bundles, and the reticular for-mation. Based on results from our experience with over 250 brainstem gliomas andvascular lesions surgically treated at the Department of Neurosurgery of Verona over



268 Albino Bricolo and Francesco Sala

the last 15 years, a map of safe “entry zones” is suggested that may guide the surgeonin choosing the least dangerous approach to this critical area. We will then criticallyreview surgical approaches to the brainstem, from the midbrain to the cervi-comedullary junction and the fourth ventricle. Finally, in the spirit of this book,those mapping and monitoring techniques that may play a role in enhancing thesafety of the different approaches will be outlined.

1 INTRODUCTION

In 1939, Bailey and colleagues described the treatment of brainstem gliomas as“a pessimistic chapter” in the history of neurosurgery [1]. Thirty years laterMatson stated that “regardless of specific histology [they] must be all classifiedas malignant tumors, since their location in itself renders them inoperable” [2].Traditionally, all tumors involving the brainstem were considered infiltrativewith diffused glial proliferation. Therefore, in consideration of the high densityof cranial nerve nuclei, fascicles, and pathways contained within the brainstem,this small part of the encephalon—approximately 6 cm high and 3.5 cm wideat the pons—has been considered untouchable by several generations of neu-rosurgeons. This attitude, which still prevails in a part of the neurosurgicalcommunity, has been progressively counterbalanced by increasing evidencethat surgical “violation” of the brainstem is safely feasible in a subgroup ofpatients. Favorable results appeared in the literature starting in the early 1980s[3–7]. More recently, brainstem surgery has been promoted by a number ofauthors who are convinced that this delicate and difficult field of surgery cannow be approached with increased confidence [8–14]. More refined imagingtechniques [15–18], better surgical techniques and equipment [4–19], andmore effective neuroanesthesia and postoperative intensive care [20–21] haveall improved the feasibility and safety of brainstem surgery. The contributionof MRI to this field has been immeasurable, given its ability to determine thatnot all tumors in the brainstem are diffuse. As a result, based on MRI, brainstemgliomas may be categorized into four groups: (1) focal; (2) cervicomedullary;(3) dorsally exophytic; or (4) diffuse. These subgroups, which reflect differentgrowth patterns, not only assist the surgeon in identifying tumor invasivenessbut also aid in selecting those tumors amenable to surgical treatment and deter-mination of prognosis [6, 11, 16, 17, 22–24]. Moreover, this grouping corre-lates well with tumor histology, since almost all diffuse tumors are infiltrative,highly aggressive lesions that are always malignant, regardless of histology atthe time of biopsy [23]. In the other groups, the great majority of tumors arebenign, low-grade astrocytomas.

During the decade of the brain, a more rational and constructive approachto the surgical management of neoplastic and vascular brainstem lesions hasemerged. Yet surgery of the brainstem remains a challenging task that requiresdeep knowledge of the microsurgical and functional correlative anatomy of the



low-grade astrocytomas. Subtotal or partial removal was done in 87% of the72 malignant gliomas, with the large majority demonstrating diffuse MRI patterns.

This series strongly confirms that brainstem gliomas have to be categorizedin distinct subgroups and no longer represent a homogeneous nosologic entityamenable only to nonspecific treatment. The focal brainstem glioma is anexpanding mass that usually dislocates neighboring nervous structures withoutinvading them, and tumor growth is infiltrative only in the subset of diffusetumors [11, 23, 27].

3 GENERAL PRINCIPLES OF THESURGICAL STRATEGY

The brainstem may be defined as the part of the neuraxis located between thediencephalon and the spinal cord, into which it continues without definiteanatomical demarcation. Comprising the midbrain, pons, and medulla oblon-gata, the brainstem is almost entirely contained in the posterior fossa, except fora small rostral portion that goes beyond the tentorial incisure and a short tract ofthe medulla oblongata that runs below the foramen magnum. Crowded by cra-nial nerve and nuclei and ascending, descending, and interconnecting fascicles,bundles, pathways, and the reticular formation, the brainstem presents a highlycomplex structure both anatomically and functionally. This makes it a neurolog-ical “minefield,” and surgical resection of brainstem tumors demands meticulousmicrosurgical technique because of the narrow routes leading to the lesion. If thetumor is exophytic or fungating out from the brainstem surface, its removalclearly begins at such an outgrowth. Thus the tumor itself creates its own entryinto the brainstem, where it may be penetrated without any risk and eventuallyremoved. Other tumors characteristically bulge without violating the brainstemsurface and may be seen under the pia or ependyma. In these cases, the accessroute for removal is also provided by the tumor itself, but much care must be paidwhen widening the entry point, given the functional significance of the sur-rounding structures, which is vital to the application and direction of microre-traction. Tumors with no surface components—the pure intrinsic tumors—require even greater care and understanding of the involved functional anatomy.With a clear mental image of the internal architecture of the brainstem and thepossible deficits that may be incurred by surgical injury, the surgeon chooses thesafest entry zones, avoiding those that could be more dangerous [28].

Entering the floor of the fourth ventricle, through which some tumors arereached, requires a clear understanding of the underlying structures (Fig.12.1). Within the small concavity of the calamus scriptorius situated above theobex and usually below the striae medullares lie two triangles of great func-tional importance: the hypoglossal triangle and the ala cinerea or vagal triangle.


Surgery of Brainstem Lesions 271

Immediately below the two medial triangles lie the hypoglossal nuclei, whichcontrol the muscles of the tongue. Because of the close proximity of the twonuclei, surgical injury to this area almost always results in severe tongue paral-ysis and atrophy. Since hypoglossal paralysis represents one of the most dev-astating cranial nerve deficits, even a minor injury in this area must be avoided.

Lateral to the hypoglossal are the vagal triangles, and under these lie thedorsal nuclei of the vagus, from where motor fibers to the bronchi, heart, andstomach originate. Slightly deeper and laterally lies the nucleus ambiguus,which gives rise to fibers of the glossopharyngeal (IX), vagus (X), and acces-sory (XI) nerves supplying musculature to the palate, pharynx, and larynx.Therefore, injury to the small concavity that forms the inferior part of therhomboid fossa, the calamus scriptorius, may result in deficits such asimpaired swallowing, dysphonia, nose regurgitation, and coughing reflex loss,thus exposing the patient to the risk of aspiration pneumonia and the inca-pacity to eat or drink [29].

The more prominent part of the median eminence, the facial colliculus, rep-resents a second highly dangerous brainstem “entry zone” through the rhomboidfossa [30]. Damage to this area invariably causes facial (VII) and abducens (VI)nerve paralysis, as well as lateral gaze disturbances due to parapontine reticularformation dysfunction. Injury to the medial longitudinal fascicles, which borderthe median sulcus and lie between the abducens and oculomotor nuclei (the

FIGURE 12.1 The positions of the cranial nerve motor nuclei are schematically projected on thedorsal surface of the brainstem (A) and outlined on the paramedian sagittal section (B). Awarenessof their location may assist in selecting the safest surgical entry zone. Modified from [11].



so-called VI–III pathway), may cause internuclear ophthalmoplegia. Despite thehigh density of neural structures involved in oculomotion, one can leave the latterquite undisturbed by entering the floor of the fourth ventricle through the mediansulcus above the facial colliculi, as long as the two medial longitudinal fascicles,which have no crossing fibers at this level, are not injured by retraction [11, 31].

Consequently, when surgical incision and microretraction on the floor of thefourth ventricle are required, four safer entries are advisable: the suprafacial, theinfrafacial, the midline above the facial colliculus, and the acoustic area. Figures12.2 and 12.3, respectively, present all the relatively safe entry zones to the dorsalbrainstem and the dangerous areas associated with expected neurological deficits.

Multiplanar MRI permits an accurate preoperative localization of the tumorand its relationship to brainstem structures. This invaluable information,together with the patient’s neurological picture and the aforementioned neuro-anatomical considerations, should all help clarify the optimal approach to sur-gical removal of a brainstem lesion. Because of the small size of the brainstem,the surgical approach must be in all senses “minimally invasive”: a surgicalmicroscope, often used at the highest magnification, fixed microretractors, anda few tiny instruments are therefore the standard tools for this type of surgery.

In the following section, we will briefly describe the major surgical routes weroutinely use to approach lesions from the upper brainstem caudally to the cer-vicomedullary junction.

3.1 MIDBRAIN

Since almost all midbrain gliomas are focal, benign astrocytomas (Table 12.1),the planned goal of surgery in this setting must be complete removal of thetumor, which will result in permanent cure. These tumors usually arise fromeither the tectal plate or the tegmentum and may extend upward to the thala-mus or downward to the pons, displacing but not infiltrating these structures[3, 32, 33]. The midbrain, which occupies the notch of the tentorium, consistsof a dorsal part (the corpora quadrigemina or tectum), a large ventral portion(the tegmentum), and the cerebral peduncles. Posterior cerebral (PCA) andsuperior cerebellar (SCA) arteries encircle the midbrain and in their course arein close relationship to the oculomotor (III) and trochlear (IV) cranial nerves.Minimizing manipulation of these normal neurovascular structures is the keyto successful extirpation of the lesion in such a constricted area [34].

Lesions of the dorsal mesencephalon in the tectal area of the quadrigeminalplate are easily approached through a standard infratentorial supracerebellarapproach popularized by Stein [35, 36] for pineal region neoplasms. This app-roach may also be used successfully for removing lower median tumors in thequadrigeminal region when an infracollicular entry is chosen to avoid ocularand auditory disturbances associated with injury to the colliculi. With a meticu-lous opening of the cerebellomesencephalic fissure and a retractor pressing



down the vermis, exposure as far down as the inferior colliculi may be obtainedwithout splitting the anterior vermis.

A particular modification of this route can be used for successful removal oflesions more ventrally placed in the tegmentum and peduncles. A semi-sittingposition and suboccipital craniotomy are the standard approach, with the excep-tion that the dural opening is extended more laterally very close to the sigmoid

FIGURE 12.2 Relatively safe entry zones into the dorsal brainstem. Supracollicular (A), infra-collicular (C), and lateral mesencephalic sulcus (B) are suitable entries for the removal of tectalmesencephalic tumors approached by the infratentorial-supracerebellar route. The median sulcusabove the facial colliculus (D), suprafacial (E), infrafacial (F), and area acoustica (G) provides safeentry for dorsal pontine tumors approached through the floor of the fourth ventricle. The posteriormedian fissure below the obex (H), the posterior intermediate sulcus (I), and the posterior lateralsulcus ( J) are sites recommended for longitudinal myelotomies to approach medullary and cervi-comedullary junction tumors. Reprinted from [31].



sinus on the side of the chosen entry: a careful dissection of the arachnoid mem-branes allows a wide opening of the cerebellomesencephalic fissure on this side.A retractor is then placed to weigh down the anterior part of the tentorial sur-face of the cerebellum. With this done, a full exposure of the lateral aspectof the midbrain is obtained. By moving the SCA and the fourth nerve, it is easyto identify the lateral mesencephalic vein, which courses into the lateral

FIGURE 12.3 Outline of the dangerous areas for entering the dorsal brainstem. Superior col-liculus (associated with visual and oculomotor disorders) (A), inferior colliculus (auditory distur-bances) (B), corpora quadrigemina (C) (as in A and B), medial longitudinal fascicles (internuclearophthalmoplegia) (D), facial colliculus (facial palsy and internuclear ophthalmoplegia) (E), facialcolliculus (immobile eyes and bilateral facial palsy) (F), facial nerve (facial palsy) (G), hypoglos-sal and vagus nuclei (dysphagia) (H), calamus scriptorius (dysphagia and cardiorespiratory dis-turbances) (I), and gracilis and cuneate tubercles (ataxia) ( J). Modified from [11].



mesencephalic sulcus. The entry is posterior to this sulcus to avoid injury to thepyramidal tract in the peduncle.

To avoid damage to the colliculi in the supracerebellar approach to tumorslocated anterior to the quadrigeminal plate, an alternative adopted by manycould be the occipital transtentorial approach [37–39], which calls for a rightoccipital craniotomy and sectioning of the tentorium adjacent to the straightsinus. The main advantage offered by this route, compared to the supracerebellarinfratentorial, is direct vision into the fissure between the superior vermis, thequadrigeminal plate, and the superior medullary velum. However, one must takeinto consideration that the occipitoparietal lobe retraction required for exposingthe falcotentorial junction may induce sensory and visual field deficits [40].

Tumors of the midbrain located near its median ventral surface may beaccessed through a pterional transsylvian route after a frontotemporal cran-iotomy as developed and extensively applied by Yasargil [41]. Following a wideopening of the sylvian fissure, the tentorial edge, third cranial nerve, andinterpeduncular cisterns are exposed. The anatomical landmark of the targetarea is the emergence of the third nerve from the midbrain with the PCA above.Below the nerve, the SCA runs medial to lateral, and the safe entry zone intothe midbrain is the small rectangular area outlined medially by the exit of thethird nerve and the basilar artery (BA), inferiorly by the SCA, superiorly by thePCA, and laterally by the tentorial edge. This narrow but fairly safe window allowssurgical access through the more medial part of the peduncle, sparing the motortract that occupies only the intermediate three fifths or so of the peduncle [11].

Tumors involving the anterolateral aspect of the midbrain can be reachedthrough a subtemporal transtentorial approach [42]. The tentorial incisure isdivided posterior to the entry of the fourth nerve, allowing exposure of theanterolateral midbrain and upper pons. This seemingly attractive route, at leastin this author’s experience, is associated with some risk because it requires tem-poral lobe retraction and thus may injure the vein of Labbé.

3.2 PONS

Tumors that involve one side of the ventral pons and fungate into the area ofthe cerebellopontine angle may be reached by a standard retrosigmoid approachthrough a lateral suboccipital retromastoid craniectomy as used in acoustic neu-roma surgery. Also, a number of diffuse gliomas appear to originate from theventral side of the pons and grow in the direction of the pontocerebellar fiberstoward the cerebellar peduncle and the cerebellopontine angle. In such cases,MRI shows the ventral pons deeply grooved by the BA and contralaterallyrotated completely to the side of the tumor, resulting in a filled cerebellopon-tine angle. With the patient in a semi-sitting position with the head rotatedtoward the side of the expansion, the bulging pons is entered through the fissure



between the stretched fifth and the seventh through eighth cranial nerves. Thediffuse tumor is then generously debulked [11].

The uncommon focal pontine tumor that is ventrolaterally placed requires acombined petrosal approach that combines subtemporal and transtentorial pre-sigmoid avenues as described by Al-Mefty [43] and Spetzler [44]. The mainadvantage of this opening is the short distance and the direct line of light to theanterolateral brainstem (Figs. 12.4 and 12.5).

FIGURE 12.4 Large cavernous malformation in the pons removed through a posterolateraltranspetrosal approach. Pre- and postoperative coronal (A) and axial (B) MRIs. Note, in the earlyT2 postoperative axial images, the route followed for removal.


FIGURE 12.5 Intraoperative microphotographs of the patient in Fig. 12.4. The right lateral aspectof the pons, encircled by the superior cerebellar artery and the trigeminal root, is directly exposed(A) and entered. The cavernoma is easily removed without any surgical injury to the neurovascu-lar structures involved (B, C).

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For tumors located in the dorsal part of the pons (and the open portion ofthe medulla), access is by a suboccipital craniotomy and trans-fourth-ventricleroute. It should be noted that the temptation of splitting the vermis during thisapproach may result in significant postoperative disturbances, such as bodytruncal ataxia, a wobbling gait, oculomotor disturbances, and cerebellar mutism[45]. In our experience [11], the vermis can be preserved by positioning thepatient in a semi-sitting position with the head fairly flexed, so that a wideexposure of the rhomboid fossa may be obtained through the cerebello-medullary fissure.

By elevating and splitting the cerebellar tonsils and displacing the posteriorinferior cerebellar arteries (PICAs), which course into the fissure itself, one canexpose the tela choroidea of the roof of the fourth ventricle, cut it at the taeniaat both sides, and then fold it back upward to expose both the lateral recesses,if necessary. Next, the tela choroidea can be divided longitudinally up to theanterior medullary velum, to which it is attached along with the choroid plexus.At that point, two strategically positioned retractors will keep the access open




and a suitable angulation of the surgical microscope will yield a complete viewof the floor of the fourth ventricle from the obex to the cerebral aqueduct. Thisroute can also be used for some tumors of the dorsal mesencephalon that dipinto the ventricular chamber, thereby avoiding possible injury to the colliculi.

For tumors further away from the midline (i.e., those located in the areaacoustica and those growing in the middle cerebellar peduncle), access can beobtained only through the ipsilateral cerebellomedullary fissure. This creates aposterolateral paratruncal route that allows for control of the region of the lat-eral recess and that of the perimedullary area on the same side.

3.3 MEDULLA AND CERVICOMEDULLARY JUNCTION

Tumors developing in the closed part of the medulla near its posterior aspectand in the cervicomedullary junction are approached through a low midlinesuboccipital craniectomy (or craniotomy) extended to the posterior arch of theatlas, followed by the necessary cervical laminotomy if the lesion extends fur-ther caudally (Figs. 12.6 and 12.7).

When the tumor is medial, it is accessed through a midline longitudinalmyelotomy and removed with a similar technique to that normally used for aspinal cord tumor (Figs. 12.8 and 12.9). For tumors laterally placed, either theposterior intermediate or the posterior lateral sulcus is used for entrance.

When the tumor is more laterally and/or ventrally located, a dorsolateralapproach is recommended. This exposure, designed by Heros [46] and imple-mented by Spetzler and Grahm [47] for vertebrobasilar junction aneurysms,provides excellent exposure of the anterolateral aspect of the medulla, the cer-vicomedullary junction, the foramen of Luschka, cranial nerves IX–XII, andassociated arteries. For removal of intra-axial lesions that expand the lowerbrainstem, it is not necessary to perform extensive bone removal of the occipi-tal condyle and the lateral mass of C1. Adequate exposure is obtained by arestricted retrosigmoid craniotomy, a C1-hemilaminectomy, and drilling awayof the posterior third of the occipital condyle.

4 POSTOPERATIVE CARE

Reviewing the first 175 of more than 250 patients operated on in Verona forintrinsic brainstem lesions, we had no intraoperative mortality, and 6 patientsdied in the first month after surgery. Despite advancements in intra- and post-operative care that have significantly reduced mortality and morbidity relatedto brainstem surgery, patients often present with new deficits or a worsening ofexisting deficits in the early postoperative period. Most of these deficits, however,


FIGURE 12.6 Comparable pre- and postoperative sagittal (A), coronal (B), and axial (C) MRIsof a dorsally exophytic astrocytoma removed via a midline suboccipital approach. A tiny sole ofnon-enhancing tumor was left over the calamus scriptorius.

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FIGURE 12.7 Intraoperative views of the same patient as shown in Fig. 12.6. The tumor bulgingat the obex is debulked (A) and then detached from the floor of the fourth ventricle (B), which islargely exposed at the end of the tumor removal (C).



FIGURE 12.8 Intrinsic ependymoma of the cervicomedullary junction. Pre- and postoperativesagittal (A), preoperative axial (B), and postoperative axial (C) MRIs showing a total removal.


FIGURE 12.9 Intraoperative microphotographs of the patient in Fig. 12.8. The dramaticallyenlarged cervicomedullary junction is exposed (A). It is entered through a midline myelotomy andthe tumor is removed with the aid of an ultrasonic aspirator during continuous lower cranial nervemonitoring (B). After radical removal of the tumor, the floor of the fourth ventricle (C) and theopened cervicomedullary junction (D) are neurophysiologically mapped. The responses from boththe left (LH) and the right (RH) hypoglossal nerves are recorded through needle electrodes insertedin tongue muscles (E).

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improve within the first few weeks, and patients are stabilized or even improvedat discharge.

The most dangerous surgical complication is palsy of the lower cranialnerves (IX–XII), which causes dyspnea and severe dysphagia, thus requiringtracheostomy and persistent attention to prevent aspiration pneumonia [21].To minimize these complications, as a rule, we keep patients in the intensivecare unit for at least 24 hr following surgery. The oral or nasal tracheal tube ismaintained with mechanical ventilation and necessary sedation. Three or 4hours after surgery a CT scan is usually taken to identify any early blood clot-ting, pneumocephalus, and hydrocephalus (although such complications arevery uncommon). Once one has a “clean” early postoperative CT scan, the tra-cheal tube may be safely removed when the patient regains consciousness andnormal ventilation parameters [31].




The removal of the tube must be done with great caution, particularly inpatients operated on for lower brainstem tumors in whom dysphagia, vocalcord paresis, and loss of the cough and gag reflexes may be expected. Also, inpatients having severe dysphagia, it has proven beneficial to delay tracheostomybecause often with sedulous care and rehabilitation training these disturbancesresolve and the patient regains the ability to swallow [48].

5 NEUROPHYSIOLOGICAL MONITORING

A detailed analysis of neurophysiological monitoring techniques relevant tobrainstem surgery is presented by Dr. Moller and Dr. Morota in Chapters 13 and14 of this book. Although classical methods of neurophysiological monitoringsuch as somatosensory evoked potentials (SEPs) and brainstem auditory evokedpotentials (BAEPs) have been extensively used in the past, it is noteworthy thatthese two methods can evaluate the functional integrity of less than 20% ofbrainstem areas [49]. Furthermore, SEPs and BAEPs are monitoring, not map-ping, techniques; therefore, they cannot help in recognizing functional land-marks in the brainstem. Displacement of a classical anatomical landmark suchas the facial colliculus is a common difficulty faced by neurosurgeons. Similarly,even when anatomy is not significantly distorted by the tumor, the identifica-tion of areas overlapping the lower cranial nerve motor nuclei can be challeng-ing. Mapping techniques are now available to intraoperatively identify motornuclei VII, X–IX, and XII on the floor of the fourth ventricle [50, 51], and pat-terns of cranial nerve motor nuclei displacement have also been recognized[51]. Results from direct stimulation of the brainstem may be invaluable inchoosing the safest approach to intrinsic tumors with no surface components.It should be stressed, however, that mapping techniques should never replacemonitoring techniques, since only these latter allow the “real-time” assessmentof the functional integrity of corticobulbar pathways and should be used anytime motor cranial nerves and nuclei are at risk of surgical manipulation orinjury.

When dealing with lesions close to the cerebral peduncle or the ventral partof the medulla, injury to the corticospinal tracts becomes a major concern to thesurgeon. Like other areas in neurosurgery, brainstem surgery has significantlybenefited from the recent introduction of intraoperative motor-evoked poten-tials (MEPs) [53, 54]. Besides continuous recording of muscle or epiduralmotor-evoked potentials [55], mapping of the corticospinal tract at the level ofthe cerebral peduncle has also become a feasible and reliable technique [56].

Neurophysiologists and neurosurgeons involved in intraoperative neuro-physiology should keep in mind that the combined use of different monitoringtechniques allows the most reliable and prompt evaluation of the functional



integrity of brainstem structures. So, although monitoring only BAEPs, onlySEPs, or only corticospinal and corticobulbar MEPs can be misleading, therational integration of data from all these modalities will provide the best pic-ture of “what is going on” in the brainstem. During surgery at the cervi-comedullary junction, monitoring of the lower cranial nerves (X–XII) shouldbe added to the same monitoring techniques used for cervical spinal cordtumors (see Chapter 4). When working on a more rostral lesion, such as a pon-tine tumor, monitoring of corticospinal and corticobulbar pathways should beintegrated with SEPs, BAEPs, and mapping of the floor of the fourth ventricle.At the midbrain level, mapping of the cerebral peduncle may be added to thebattery of neurophysiological tests.

Neurophysiological data should never replace a detailed knowledge of brain-stem functional anatomy, careful interpretation of the MRI, and an extremelygentle and refined surgical technique. Nevertheless, monitoring and mappingtechniques are becoming increasingly valuable as tools in the hands of thoseneurosurgeons who approach this “forbidden area” of the central nervoussystem. From a neurophysiological perspective, postoperative swallowing andeye movement coordination deficits remain unsolved problems. It has beendocumented that swallowing problems may develop in spite of intraoperativelypreserved corticobulbar MEPs. Besides descending cortical control of the motornuclei of the glossopharyngeal and vagal nerves, preservation of the afferentarch of this reflex as much as of the interneurons involved in the coordinatedact of swallowing is necessary for preserving normal function. Internuclear oph-thalmoplegia is also far from being solved, since monitoring and mapping of theinternuclear fascicles have not yet been developed.

6 CONCLUSION

A hopeless attitude when facing brainstem tumors is no longer justified, at leastin subgroups of patients who could significantly benefit from surgery [57, 58].Our personal experience with over 250 tumors confirms the increasing evi-dence that surgical “violation” of the brainstem is safely feasible when selectioncriteria are followed. In our opinion, surgery should be recommended as the“first choice” for almost all focal tumors and for that subset of diffuse gliomasprotruding into the cerebellopontine angle or bulging at the external aspect ina relatively silent area. Together with improvements in neuroimaging, surgicaltechnique, and intra- and postoperative intensive care, neurophysiologicalmonitoring has now established its role in further improving the results of thischallenging surgery.



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43. Al-Mefty, O. (1990). Surgical exposure of petroclival tumors. In “Neurosurgery update: I. Diag-nosis, operative technique, and neurooncology” (R.H. Wilkins, and S.S. Rengachary, eds.),pp. 409–414. McGraw-Hill, New York.

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45. Ersahin, Y., Mutluer, S., Saydam, S., and Barcin, E. (1997). Cerebellar mutism: Report of twounusual cases and review of the literature. Clin. Neurol. Neurosurg., 99, 130–134.

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49 Fahlbusch, R., and Strauss, C. (1991). The surgical significance of brain stem cavernoushemangiomas. Zentralbl Neurochir., 52, 25–32.

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C H A P T E R 13

Monitoring and Mappingthe Cranial Nerves and the BrainstemAAGE R. MØLLER

Callier Center for Communication Disorders, University of Texas at Dallas, Dallas, Texas

1 Introduction2 Monitoring Cranial Motor Nerves

2.1 Monitoring the Facial Nerve2.2 Monitoring the Motor Portion of the

Trigeminal Nerve (CN V)2.3 Monitoring Cranial Nerves That Innervate

the Extraocular Muscles2.4 Monitoring Other Cranial Motor Nerves

3 Monitoring Sensory Cranial Nerves3.1 Monitoring the Auditory Nerve3.2 Monitoring the Optic Nerve3.3 How Large a Change is Allowed?

4 Monitoring the Brainstem5 Mapping the Floor of the Fourth Ventricle6 Monitoring That Can Guide the Surgeon

During an Operation6.1 Hemifacial Spasm6.2 Mapping the Auditory-Vestibular Nerve6.3 Mapping the Trigeminal Nerve


ABSTRACT

Monitoring cranial nerves in skull base operations has been proven to reduce the riskof permanent postoperative neurological deficits. The most frequently monitoredcranial nerves are the auditory and the facial nerves, which are at risk in operationsin the cerebellopontine angle. Lower cranial nerves (CN IX, X, XI, and XII) are at risk



292 Aage R. Møller

in operations affecting the lower skull base, and monitoring the cranial motor nervesthat innervate the extraocular muscles is beneficial in many skull base operations.Monitoring brainstem auditory evoked potentials (BAEPs) is useful when monitor-ing the overall function of the brainstem in operations where the brainstem is sur-gically manipulated or compressed, particularly in operations of large acoustictumors. In some operations it has been possible to use electrophysiological methodsto aid the surgeon in achieving the therapeutic goal of the operation. Examples areoperations for hemifacial spasm, for vestibular neurectomy, and for whenever it isimportant to find safe entry to the brainstem from the floor of the fourth ventricle.Monitoring the sensory part of CN V has not found general use, but mapping thatnerve can help the surgeon make a selective section of the nerve.

This chapter reviews methods for intraoperative localization and monitoring ofcranial motor nerves. It describes methods of monitoring the neural conduction in theauditory nerve using recordings of BAEPs and evoked potentials recorded directlyfrom the CN VIII. Methods for recording an electromyogram (EMG) from musclesinnervated by cranial motor nerves are also detailed. Intracranial electrical stimula-tion of the respective cranial nerves is described, as is mapping of CN V, CN VIII, andthe floor of the fourth ventricle for finding safe entry points to the brainstem.

1 INTRODUCTION

Intraoperative neurophysiologic monitoring of cranial nerves is now used inmany kinds of neurosurgical operations. This monitoring can improve surgicaloutcome by several means. It can help reduce the risk of surgically inducedinjuries, aid in proper identification of specific neural structures, and, in a fewoperations, can also ensure that the therapeutic goal of an operation is achievedbefore the operation is ended. Whereas imaging methods, such as MRI, arerestricted to detecting structural changes or coarse changes in function throughmeasurements of oxygen consumption, neurophysiologic monitoring is aninexpensive and effective method for detecting changes in functional integrity.

Methods for monitoring the facial nerve were the first to be described [1–4], fol-lowed by intraoperative monitoring of the neural conduction in the auditory nerve[5–8]. These techniques came into general use in operations in the cerebellopon-tine angle during the 1980s [4, 9–12]. Operations on large skull base tumors weredeveloped during the same period [13–15], and subsequently methods for intra-operative monitoring of several other cranial nerves were introduced [7, 8, 15, 16].The work by these and other investigators has led to techniques that optimize theuse of intraoperative monitoring for a growing number of surgical procedures.

2 MONITORING CRANIAL MOTOR NERVES

The general principles of monitoring cranial motor nerves include the use of ahand-held electrical stimulating electrode to probe the surgical field while elec-tromyographic (EMG) potentials are recorded from muscles that are innervatedby the respective cranial nerve. That method was developed in connection with


monitoring the facial nerve in operations for tumors of the acoustic nerve, andit makes it possible to identify regions of a tumor where there is no (motor)nerve present. The same method can be used to determine the anatomical loca-tion of cranial motor nerves in the surgical field and to preserve their functionalintegrity. Continuous monitoring of muscle activity helps the surgeon preservethe postoperative function of cranial motor nerves because it can detect whensurgical manipulation has caused injury to the nerve.

2.1 MONITORING THE FACIAL NERVE

The introduction of intraoperative monitoring of the facial nerve was promptedby the high incidence of loss of facial function in operations for tumors of theacoustic nerve. The principle of probing the surgical field with a hand-heldelectrode has not changed since such monitoring was introduced in the 1960s,but the way that muscle contractions are monitored has been modified. Earlyin the history of facial nerve monitoring, the face of the patient was observedby an assistant [1, 2], later, contractions of face muscles were converted intoelectrical signals using mechanotransducers [3, 9]. Now, contractions of facialmuscles are usually detected by recording an electromyogram from facial mus-cles [4, 8, 10–12, 16, 17].

The first goal of facial nerve monitoring in operations of large acoustictumors is to find regions of the tumor that do not contain any portion of thefacial nerve so that one can rapidly remove large portions of the tumor with lowrisk of permanently injuring the facial nerve. That is done most efficiently byusing a monopolar hand-held stimulating electrode to probe the tumor whileobserving EMG potentials recorded from electrodes placed in face muscles.Short, constant-voltage impulses are the most suitable stimuli [4, 8, 12, 16].

A monopolar stimulating electrode that is insulated except at the tip willactivate a nerve that is located within a sphere around the tip of the electrode.The size of that sphere depends on the stimulus intensity. The larger the stim-ulus intensity, the larger the diameter of the sphere, and thus the larger thevolume of tissue in which nerves will be activated. It is therefore important touse adequate stimulus strength so that all nerve fibers are activated in a suffi-ciently large volume of tumor. If the stimulus is too weak, the facial nerve maybe located closer to the stimulating electrode than the surgeon has expected andthe portion of the tumor that is removed may contain parts of the facial nerve.Probing the tumor with a stimulus that is too strong may give the impressionthat the facial nerve is closer to the stimulating electrode than it is, and that willslow down tumor removal.

When a nerve is stimulated electrically, it is important that the currentthrough the nerve is affected as little as possible by external factors such as the

Monitoring and Mapping the Cranial Nerves and the Brainstem 293Monitoring and Mapping the Cranial Nerves and the Brainstem 293


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electrode impedance or by shunting of current by cerebrospinal fluid (CSF).When stimulating peripheral nerves through electrodes placed on the skin, itis common to use a stimulator that delivers a constant current because the elec-trode impedance is likely to change. Ohm’s law reveals that constant-currentstimulation maintains a constant current independent of the electrode resis-tance; that is, the current through the nerve will be independent of changes inelectrode impedance or skin resistance. The situation is different when stimu-lating inside the skull, where the stimulating electrode is likely to be submergedin CSF at certain times whereas the surgical field may be relatively dry at othertimes. Therefore, the shunting of applied electrical current will vary as theamount of CSF in the surroundings changes, but variations in the electrodeimpedance is of less importance. Again, Ohm’s law reveals that shunting of cur-rent will not affect the current delivered to any volume of tissue when the stim-ulator delivers a constant voltage. Thus a constant-voltage stimulator will deliveran electrical current to a nerve in the operative field that varies less than thatdelivered by a constant-current stimulator. Consequently, constant-voltagestimulation will provide a nearly constant stimulation of a nerve that is embed-ded in a tumor and from time to time submerged in CSF [4, 16]. For this reason,constant-voltage stimulators are preferred over constant-current stimulators forelectrical stimulation of an intracranial portion of the cranial nerve in the oper-ative field. Whereas a stimulator can be designed to deliver a constant voltage,the stimulating electrode has a certain impedance and that makes the stimula-tion semiconstant. Such stimulation is less dependent on current shunting thanif a constant-current stimulator is used.

The second goal of facial nerve monitoring is to identify all parts of the facialnerve. A monopolar stimulating electrode can be used for that purpose, but abipolar electrode has greater spatial selectivity and is therefore more suitable fordetermining of the exact location of a nerve [18]. However, a monopolar stim-ulating electrode is more suitable for probing a tumor for the presence of thefacial nerve because the volume of tissue that a bipolar electrode stimulatesdepends on the electrode’s orientation. Ideally, one would thus prefer to haveboth a monopolar and a bipolar stimulating electrode available in operationswhere motor nerves are at risk of being injured. It is important to use the opti-mal stimulus strength for the task of finding the facial nerve, particularly if amonopolar stimulating electrode is used. The stimulus strength should be kepthigh in the beginning, and when a response is obtained, it should be reducedto find the exact location of the facial nerve. Watching the amplitude of theEMG response while probing the surgical field can provide information aboutthe location of the nerve relative to the stimulating electrode and thus facilitateits rapid identification. If the amplitude of the EMG response decreases whenthe stimulating electrode is moved, it is a sign that the stimulating electrodemoved away from the facial nerve, whereas an increase in the response amplitude


Monitoring and Mapping the Cranial Nerves and the Brainstem 295

indicates that the stimulating electrode was moved toward the facial nerve.When the response reaches supramaximal amplitude, the stimulus strengthsmust be decreased to find the direction of the facial nerve.

The third goal of facial nerve monitoring is to detect when injuries haveoccurred to the facial nerve. Continuous monitoring of facial EMG in theabsence of electrical stimulation is useful for that purpose. Normally, no orvery little EMG activity should be present in the absence of electrical stimula-tion of the facial nerve, but injury to the facial nerve may generate various kindsof EMG activity. Such activity may only occur when the facial nerve is surgi-cally manipulated, or it may last for shorter or longer periods after the surgicalmanipulation has ended [17, 19–21]. Short periods of EMG activity may notindicate that the facial nerve has been permanently injured. However, the like-lihood that a patient will have postoperative facial weakness increases if suchEMG activity occurs frequently or for long periods.

Mechanical stimulation of a normal (uninjured) facial nerve normally produceslittle or no activation of facial muscles. Slightly injured nerves are likely to becomemore sensitive to mechanical stimulation, whereas severely injured nerves do notrespond to mechanical stimulation. Slightly injured nerves may act as impulsegenerators, which explains the spontaneous facial activity that can result from sur-gical manipulations. However, the absence of mechanically induced EMG activitydoes not guarantee that injury has not occurred to the facial nerve. Electrical stim-ulation must therefore always be used to verify that the facial nerve has not beeninjured. Prolonged latency and decreased amplitude of the EMG potentials evokedby electrical stimulation of the facial nerve are signs of injury.

2.1.1 Recording Facial EMG Potentials

Investigators have suggested different ways of recording EMG potentials fromthe facial muscles. Some have used two recording channels, one connected toelectrodes placed in facial muscles of the upper face and the other recordingEMG potentials from muscles of the lower face. Since the purpose of facialnerve monitoring is to avoid injury to any part of the facial nerve, it is not nec-essary to differentiate between different parts of the face when recording EMGpotentials, and a single recording channel is therefore sufficient for monitoringEMG activity. Recording from muscles of the entire face can be accomplishedby placing one of the two recording electrodes that are connected to a differ-ential amplifier in the orbicularis oculi muscles and the other in the orbicularisoris muscles (Fig. 13.1A). (EMG potentials are best recorded using needle elec-trodes that are secured by adhesive tape that has micropores, e.g., 3M’s Blen-derm 3M Health Care, St. Paul, MN.)

The motor portion (portio minor) of the trigeminal nerve may be stimulatedwhen probing large acoustic tumors to find the facial nerve eliciting contractions


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of the muscles of mastication (masseter and temporalis muscles). Because of thespread of EMG activity, that activity from these muscles may be picked up bythe recording electrodes that are placed in facial muscles and become mistakenfor contractions of the facial muscles, causing misidentification of the facial nerve.The peak latency of the response to stimulation of the trigeminal nerve is less

FIGURE 13.1 (A) Illustration of placement of recording electrodes for recording facial EMG andEMG from the masseter muscle. (B) Responses from facial muscles and the masseter muscles tointracranial electrical stimulation of the facial and the trigeminal nerves, respectively, from elec-trode placement as shown in (A). Reprinted from [8].



than 6 ms (masseter muscle), and the peak latency of the response from thefacial muscles (orbicularis oris/oculi) to intracranial stimulation of the facialnerve is longer than 8 ms. The latency of the beginning of the masseter muscle’sresponse to intracranial stimulation is 1.5–2.0 ms for the trigeminal nerve and5–6 ms for the facial nerve (Fig. 13.1B). If a second recording channel is avail-able, it is best to use it to record directly from the mastication muscles such asthe masseter muscle (Fig. 13.1A).

Monitoring of neural conduction in the facial nerve is facilitated by makingthe recorded EMG potentials audible [4, 17], but it is also important to displaythe EMG potentials on an oscilloscope to make it possible to measure theiramplitude and latency. When the recorded EMG potentials are audible, thestimulus artifact should be suppressed from reaching the loudspeaker [4]. Thatfeature is now available in most commercial equipment. Some commercialequipment designed for facial nerve monitoring produces a tone signal whenthe EMG potentials reach a certain preset amplitude. However, the direct soundof the EMG signal contains much valuable information that is lost when onlythe tone signals are presented through the loudspeaker.

EMG potentials cannot be recorded if muscle relaxants are used. It is there-fore important to use an anesthesia regimen that does not include paralyzingagents. To prevent accidental muscle paralysis from the application of relaxants,the monitoring team must maintain good communication with the anesthesi-ologists during an operation.

It has been suggested that testing of the neural conduction of the facial nervein operations for tumors of the cerebellopontine angle might aid in makingdecisions regarding the feasibility of grafting the facial nerve in the same oper-ation. Absence of an EMG response to electrical stimulation of the facial nerveat a strength that normally elicits a maximal EMG response indicates a totalconduction block peripherally to the stimulated site. However, such a block ofneural conduction may be caused by different kinds of injuries to the nerve. Ifit is caused by neurapraxia, the nerve will recover in a short time without anyintervention. If the cause of the conduction block is axonotmesis, the nerve willregrow spontaneously and function will be regained after 8–12 months withoutany intervention. Only if the injury is caused by neurotmesis is it appropriateto graft the facial nerve, but neurotmesis cannot be distinguished from neu-rapraxia or axonotmesis by electrophysiologic measures. That can only beassessed by visual observation of the nerve.

Injury to the facial nerve in the beginning of the operation, to the extent thatblockage of neural conduction occurs, should be avoided because it will makeit impossible to monitor the facial nerve during the rest of the operation, evenif the cause of the neural conduction block is neurapraxia.

Continuous monitoring of the facial nerve has been previously described[22]. The method described by Colletti et al. (1997) [22] makes use of record-ings of antidromic potentials from the facial nerve that are elicited by electrically


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stimulating the marginal mandibular nerve and that are recorded from the facialnerve intracranially. This method is still in its infancy but will probably becomea clinically useful method in the future.

2.2 MONITORING THE MOTOR PORTION

OF THE TRIGEMINAL NERVE (CN V)

The motor portion (portio minor) of the trigeminal nerve can be monitored byrecording EMG potentials from the masseter muscle, as already described(Fig. 13.1). Such monitoring helps reduce the risk of injuring the trigeminalmotor nerve (portio minor, CN V) in operations for large acoustic tumors and forother skull base tumors in the regions of the brain where the trigeminal nerve ispresent.

2.3 MONITORING CRANIAL NERVES THAT

INNERVATE THE EXTRAOCULAR MUSCLES

Cranial nerves IV and VI and the motor portion of CN III can be identified inthe surgical field in a similar way as that described for the facial nerve: by usinga hand-held electrical stimulator and recording EMG potentials from the mus-cles that these nerves innervate. Regions of a tumor that do not contain anyparts of these cranial nerves can be identified by probing the tumor with a hand-held electrical stimulating electrode.

EMG potentials from the muscles that are innervated by these cranial nervescan be recorded by placing needle electrodes percutaneously so that they comein close proximity to the respective muscles [7, 8, 15] (Fig. 13.2). The CN VIis monitored by recording from the lateral rectus muscle, and CN III can bemonitored by recording from the medial rectus muscle. Recordings from thesuperior oblique muscle can monitor neural activity in CN IV [7, 8]. Monopo-lar recording electrodes are used rather than bipolar electrodes because of insuf-ficient space to place bipolar electrodes. The reference electrodes are placed onthe opposite side of the head to avoid recording EMG activity from facial mus-cles on the operated side of the head, where they may be activated by surgicalmanipulation of the facial nerve (Fig. 13.2), assuming that the facial nerve onthe opposite side has not been manipulated.

An alternative to invasive placement of electrodes for recording EMG poten-tials from the extraocular muscles was described by Sekiya and coworkers [23].Instead of using needle electrodes, these investigators placed wire loops underthe eyelids to record EMG potentials. The amplitude of the recorded EMG



potentials is smaller than that obtained using needle electrodes but sufficientlylarge for direct display on an oscilloscope.

2.4 MONITORING OTHER CRANIAL

MOTOR NERVES

The motor portion of lower cranial motor nerves CN IX, CN X, CN XI, and CNXII can be monitored using methods similar to those described for the facialnerve. These are mixed nerves containing sensory and autonomic fibers inaddition to motor fibers. It is not practical to monitor these other populations

FIGURE 13.2 Placement of electrodes for recording EMG responses from the extraocular mus-cles (CN III, CN IV, CN VI), the facial muscles (CN VII), the masseter muscle (portio minor of CNV), the tongue (CN XII), and the neck muscles (CN XI). Also shown is electrode placement forrecording BAEPs and visual evoked potentials (VEP), placement of an earphone for presentingclick stimuli, and a contact lens with light-emitting diodes for stimulating the eye. Reprintedfrom [24].


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of nerve fibers, but it is assumed that if motor fibers are not injured the sensoryand autonomic fibers are also intact. Thus EMG potentials from muscles inner-vated by mixed nerves can be assumed to represent the entire nerve, and thelower cranial nerves can be monitored by recording EMG potentials from mus-cles innervated by these nerves.

The motor portion of the glossopharyngeal nerve (CN IX) is monitored byplacing needle electrodes in the soft palate [2, 8, 16, 24]. The vagus nerve (CN X)can be monitored by placing receding electrodes in the vocal folds [16] torecord EMG potentials from laryngeal muscles. This must be done with a laryn-goscope and requires expert assistance. Some tracheal tubes have electrodesbuilt in for recording EMG potentials from larynx muscles, which can also berecorded from needle electrodes that are placed percutaneously in the larynxmuscles [25]. The spinal accessory nerve (CN XI) is monitored by recordingEMG potentials from neck muscles (e.g., the trapezius muscle).

The hypoglossal nerve (CN XII), the main function of which is to control thetongue, is at risk in operations of tumors of the clivus. A lesion of the hypoglos-sal nerve is serious, and bilateral loss of that nerve is devastating. It is a verysmall nerve that is often totally obscured in the surgical field. The techniquedescribed for finding the facial nerve is equally effective in finding the hypoglos-sal nerve. Recording EMG potentials from the tongue [16, 24] (Fig. 13.2) usingneedle electrodes is suitable for monitoring EMG potentials evoked by intracra-nial stimulation of the CN XII.

Although the amplitude of the recorded EMG potentials obtained from thesedifferent muscles varies, it is usually sufficient to directly observe the EMGpotentials on an oscilloscope. Monitoring many cranial motor nerves requiressimultaneous display of the EMG potentials recorded from one muscle for eachof the nerves that are monitored. It is useful to make the EMG audible, but onlyone channel can be made audible at one time.

There are some risks involved in stimulating motor nerves electrically. Forexample, stimulating the vagus nerve in this way may affect vital organs suchas the heart. Since it is particularly risky to use a high stimulating rate, the stim-ulus rate should be kept low (2–4 pps). Electrical stimulation of motor nervessuch as CN XI that innervate large muscles also involves risk because suchstimulation may activate many motor units in synchrony, which does not occurwhen the muscles are activated voluntarily. Electrical stimulation of a motornerve can therefore produce more muscle force than do the usual voluntarymovements and can possibly injure the muscle or its tendons. Also, the naturalfeedback from tendon organs that normally prevents excessive forces is notfunctional when the motor nerve is stimulated directly. It is therefore impor-tant that caution is exercised whenever one is electrically stimulating motornerves to large muscles.



3 MONITORING SENSORY CRANIAL NERVES

The auditory nerve is the most commonly monitored cranial sensory nerve.The sensory portion of the trigeminal nerve (portio major) or the sensory partof mixed nerves is rarely monitored. As described previously, it is the motorportions of mixed cranial nerves that are usually monitored because it is tech-nically easier than monitoring sensory nerves.

3.1 MONITORING THE AUDITORY NERVE

The auditory nerve is especially at risk during operations in the cerebellopon-tine angle. It may be injured from surgical manipulations or from heating fromelectrocoagulation, which results in changes in the neural conduction of thenerve. Several monitoring methods are currently used for detecting suchchanges in neural conduction in the auditory nerve. Recording of far-field audi-tory evoked potentials (brainstem auditory evoked potentials, BAEPs), alsoknown as auditory brainstem responses (ABRs), is the most commonly usedmethod for such monitoring [5, 8, 26–33]. Recording BAEPs requires littlepreparation, but it takes a relatively long time to obtain an interpretable recordbecause the amplitude of these potentials is very small. In the other methodused for monitoring neural conduction in the auditory nerve, the auditoryevoked potentials are recorded directly from the exposed CN VIII [34–36] orfrom the surface of the cochlear nucleus [37, 38]. Direct recordings from CNVIII and the cochlear nucleus have the advantage of providing almost instanta-neous information about changes in neural conduction in the auditory nerve,but these methods can only be used when the appropriate structure is exposedsurgically, and they require that the surgeon position the recording electrode.

3.1.1 Techniques for Recording BAEPs

The technique used for recording BAEPs in the operating room is similar to thatused in the clinic, with some important differences. It is important to obtain aninterpretable record in a short time in the operating room, and the electricalnoise that typically occurs in operating rooms needs to be addressed to moni-tor BAEPs intraoperatively. The following can reduce the time it takes to obtainan interpretable record:

1. Reduce electrical interference2. Use optimal electrode placement3. Use optimal filtering4. Use optimal stimulus intensity and repetition rate


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The ratio between the amplitude of the recorded potentials and the back-ground noise (the signal-to-noise ratio) determines how many responses mustbe added in order to obtain an interpretable record. Reduction of electricalinterference can therefore reduce the number of responses that must be addedand thus the time it takes to detect a change in neural conduction time of theauditory nerve. The ongoing electrical activity from the brain (EEG) and theactivity from muscles (EMG) are also recorded by the electrodes used to recordBAEPs. These biological potentials reduce the signal-to-noise ratio and thusincrease the number of responses that must be added to obtain an interpretablerecord. Optimal electrode placement can reduce such interference.

The use of optimal filtering can decrease the time it takes to obtain an inter-pretable record because it reduces the noise more than the signal. Using opti-mal stimulus intensity ensures the highest amplitude of the BAEP.

3.1.1.1 Reducing Interference

Signal averaging (adding responses) is a relatively slow way to improve thesignal-to-noise ratio because the ratio only improves by the square root of thenumber of responses that are added. This makes it imperative to reduce the elec-trical interference as much as possible, and that can only be done by meticu-lously studying the operating room and its electrical installations. The best timeto do this is when no operation is being performed, such as often occurs in thelate afternoon. Then it is possible to switch equipment on and off while watch-ing its effect on evoked potentials recorded from a dummy or from a volunteerwho is wired up in a similar way as a patient. An oscilloscope connected directlyto the output of the physiologic amplifiers (before the signal is routed to theanalog to the digital converter) is the necessary tool for such work. The use ofan antenna connected to an amplifier with an oscilloscope attached is also aneffective means of identifying sources of electrical interference [8].

Magnetic interference may occur from transformers in the power supply, forinstance, for the light source of microscopes. This interference affects record-ing because it induces electrical current in the electrode leads. The source ofmagnetic interference may be identified in a similar way as that used for iden-tifying static electric interference, by using a coil connected to an amplifier [8].To reduce the interference from magnetic fields, the electrode wires should bekept as short as possible and the wires should be twisted. That will reduce thepickup of both electrical and magnetic interference. Wire loops can pick upmagnetic interference and should be avoided.

Interference may appear unexpectedly during monitoring. To detect suchinterference, the recorded potentials should be displayed directly on an oscillo-scope that is connected to the output of the physiologic amplifiers. To identifythe nature of the interference, which is a prerequisite for eliminating the inter-ference, one must inspect the displayed waveform of interference. Display of the



averaged potentials does not provide such information, and it is difficult toidentify the interference by observing the waveform of the averaged potentials.If not watched directly on an oscilloscope, the interference becomes apparentonly by an increase in the number of rejected responses.

3.1.1.2 Electrode Placement

Recording electrodes should be placed so that they record the BAEPs with thehighest amplitude while recording as little EEG and muscle EMG as possible.Recording electrodes placed on the vertex and earlobe fulfill that requirement.

It may be advantageous to record BAEPs in two planes [8]. Two pairs ofelectrodes are used, one pair placed at the vertex and upper neck, and the otherpair placed at the earlobe. The electrodes are connected to separate amplifiers,and the responses are averaged and displayed separately. The earlobe–earlobeelectrodes will record peaks I–III of the BAEPs with a higher amplitude than thevertex–neck electrodes, which in turn will record peak V with a higher ampli-tude than the earlobe–earlobe electrodes.

The BAEP recorded in patients with hearing loss usually has a lower amplitudethan that recorded in individuals with normal hearing, and the waveform is oftenless well defined. The BAEPs in individuals with acoustic tumors have a low ampli-tude and prolonged latencies. It is therefore a greater challenge to obtain an inter-pretable BAEP in individuals with hearing loss than it is in individuals who havenormal hearing preoperatively. It takes a longer time to obtain an interpretablerecord in patients with tumors of the acoustic nerve than in other patients, andtherefore changes in neural conduction in the auditory nerve are detected later.Also, injuries to the auditory nerve affect the BAEP more than do injuries to thecochlea. As an operation proceeds, temporary or permanent injury to the auditorynerve may occur; that will further impair the quality of the BAEP and prolong thetime it takes to detect a change in neural conduction in the auditory nerve.

3.1.1.3 Stimulation

Clicks are the common form of stimuli used both in the clinic and in theoperating room, and the stimulus intensity should be as high as possible with-out involving a noticeable risk for noise-induced hearing loss. Approximately105 dB PeSPL, corresponding to approximately 65–70-dB hearing level (HL)when presented at a rate of 20 pps, is appropriate. The optimal repetition rateis 30–40 pps [8], but often a much lower rate is used. When recording BAEPsunder the best circumstances, i.e., in individuals with normal hearing when theelectrical interference is low, one must add at least 1000 responses to obtain aninterpretable record. Using a repetition rate of 10 pps, as is common in theclinic, means that it would take 100 s to obtain an interpretable record. Usinga stimulus rate of 30 pps would reduce the time to 30 s.



without introducing phase shift (zero phase filters), which is unavoidable whenusing electronic filtering. Phase shifts cause changes in the latencies of responsessuch as BAEPs.

3.1.2 Recording Directly from the Exposed Auditory Nerve

The compound action potential (CAP) that is recorded in response to clicksfrom the exposed intracranial portion of the CN VIII has been used for moni-toring in operations for tumors of the acoustic nerve [36, 41] and in microvas-cular decompression operations [30, 35]. When recorded with a monopolarelectrode, these potentials have much larger amplitudes than BAEPs [34, 35,42]. The CAP recorded directly from the auditory nerve can therefore beviewed directly on an oscilloscope, or an interpretable record can be obtainedafter only a few responses have been added. That means that such recordingsprovide nearly instantaneous monitoring of neural conduction in the portionof the auditory nerve that is located peripherally to the recording electrode.

The waveform of the recorded CAP is similar to that recorded from a longnerve using a monopolar recording electrode, i.e., an initial positive deflectionfollowed by a large negative peak, which is followed by a smaller positive poten-tial (Fig. 13.4). The waveform of the CAP is affected by hearing loss [43] andis typically more complex in individuals who are hard of hearing than in indi-viduals with normal hearing.

Stretching the auditory nerve typically reduces its conduction velocitywhich is reflected by an increased latency of the negative peak of the CAP. Con-duction block in some nerve fibers results in decreased amplitude of the nega-tive peak of the CAP, while the amplitude of the initial positive peak increases(Fig. 13.4). A total conduction block results in the total absence of a negativepeak, and the CAP consists of a single positive deflection. This is known as a“cut end” potential.

Recordings directly from the exposed CN VIII can only be done when theauditory nerve is exposed, and the recording electrode must be kept in place onthe nerve during the operation [8]. CN VIII is more sensitive to mechanicalmanipulation than other cranial nerves in the cerebellopontine angle because it iscovered with central myelin (oligodendrocytes) over its entire intracranial courseand has no perineurium. Thus CN VIII’s glial transition zone (Obersteiner-Redlich zone) is located in the internal auditory meatus, just inside the porusacusticus, whereas in other cranial nerves of the cerebellopontine angle thetransition zone between peripheral and central myelin is located close to thebrainstem, leaving only a few millimeters of the nerve covered with centralmyelin [44]. In addition, there are indications from animal experiments thatmanipulations of CN VIII intracranially that cause the nerve to be pulled in a


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medial direction may cause injury to the nerve deep within the internal audi-tory meatus. The recording electrode must therefore be soft and exert minimalpressure on the nerve [8]. We have used a multistrand, Teflon-insulated silverwire to which uninsulated tips of cotton wick are sutured [8, 34, 35]. Onemajor problem is that the electrode may easily be dislocated during surgicalmanipulations. Many of the problems associated with recording directly fromthe exposed eighth nerve can be eliminated, however, by instead recording fromthe surface of the cochlear nucleus [38].

3.1.3 Recording Directly from the Cochlear Nucleus

The cochlear nucleus is the floor of the lateral recess of the fourth ventricle,and recordings from the cochlear nucleus can therefore be made by placing anelectrode in the lateral recess of the fourth ventricle [35, 38, 45] (Fig. 13.5A).A cotton wick electrode similar to the one used to record from the exposed

FIGURE 13.4 Examples of changes in the waveform of CAP recorded from the proximal portionof the intracranial part of the auditory nerve during a microvascular decompression operation. (A)Normal waveform. (B) Beginning coagulation showing how spread of heat to the nerve graduallyimpairs the response. Reprinted from Møller, A.R. (1988). “Evoked potentials in intraoperativemonitoring.” Williams & Wilkins, Baltimore, MD.


FIGURE 13.5 (A) Illustration of placement of the electrode for recording evoked potentials fromthe cochlear nucleus. (B) Waveform of recorded potentials. Top tracings: BAEP; middle tracings:CAP recorded directly from the intracranial portion of CN VIII; bottom tracings: response recordedfrom the surface of the cochlear nucleus as shown in (A). The stimuli for all recordings were clicks,105 dB PeSPL. Solid lines: rarefaction clicks; dashed line: condensation clicks. Reprinted from [38].

307


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eighth nerve is suitable for such recordings. The electrode may be pushedthrough the foramen of Luschka to reach the floor of the lateral recess.Recording from the cochlear nucleus yields potentials of similar amplitudeto those recorded from the exposed eighth nerve (Fig. 13.5B), but the record-ing electrode is out of the surgical field and is not disturbed by surgicalmanipulations in operations in the cerebellopontine angle. Useful recordingscan also be obtained by placing the electrode on the CN X where it enters thebrainstem.

3.2 MONITORING THE OPTIC NERVE

Recordings of visual evoked potentials from electrodes placed on the scalp areused in operations where the optic nerve is at risk. It is also technically possi-ble to record CAPs from the optic nerve during operations in which it isexposed [7].

The choice of stimulus to evoke the visual response in the operating room islimited to brief light flashes. Such stimuli evoke a clearly recordable response,but the changes in such visual evoked potentials to flash stimulation that mayoccur intraoperatively are not directly related to injuries of the optic nerve orthe optic tract [46]. This is probably because the visual system is not specifi-cally responding to the time pattern of light stimuli. This fact has been recog-nized clinically, and therefore diagnostic tests using visual evoked potentialsfollow a checkerboard pattern of changing contrasts as stimulus. Such a stim-ulus cannot be used in the anesthetized patient because it requires a focusedpattern on the patient’s retina. Recently, it has been suggested that theresponses to high-intensity light flashes are better indicators of injuries to theoptic nerve than responses to less intense light flashes [47].

3.3 HOW LARGE A CHANGE IS ALLOWED?

The question of how large a change in the latency of peak III or peak V of theBAEP is “safe” and does not require any action from the surgeon has beendebated extensively. Some authors have stated that there is no need to takeaction even when large changes in the BAEP occur [27], while others [8] haveexpressed the opinion that any small change in the latency implies a certain(small) risk of change in hearing postoperatively.

Measurements of changes in neural conduction of the auditory nerve onlyprovide information about the likelihood of acquiring a permanent hearingimpairment. That means that a certain increase in latency of recorded evoked



potentials means that there is a likelihood of postoperative hearing loss of a cer-tain magnitude. Therefore, the allowable change in latency depends on howlarge a number of individuals can be allowed to acquire a permanent hearingloss of a certain magnitude. Information about the relationship between latencyshift and the likelihood of permanent hearing loss is difficult to obtain becausea large number of patients must be studied. It is not known if there is a saferange of latency changes in which there is no risk of permanent hearing loss.The time during which the latency is increased most likely also plays a role, andit is likely that a concomitant decrease in amplitude influences the outcome[28]. As a further complication, the meaning of “safe” varies among investiga-tors, and so does the definition of “no noticeable hearing loss” (i.e., the amountof allowable hearing loss).

Our experience from monitoring a large number of patients who were oper-ated on for disorders of cranial nerves V, VII, and VIII (due to vascular com-pression) leads us to believe that there is no threshold. This means that the riskof permanent postoperative hearing loss increases from very small shifts inlatency of the BAEP. Thus intervention by the surgeon is justified when anydetectable change (i.e., changes that are larger than those that occur when nooperation is performed) in the latency occurs. This emphasizes the importanceof reversing even small changes in intraoperative recordings.

It is noteworthy that the quality of life was reduced in a large fraction ofpatients who had no postoperative neurological deficits that were detectableusing objective testing [48]. This would suggest that detrimental changes didoccur that were beyond the scope of the objective tests used.

4 MONITORING THE BRAINSTEM

Intraoperative monitoring of BAEPs can provide information about the gen-eral condition of the brainstem, and BAEPs are generally monitored in oper-ations where the brainstem is being manipulated [7, 8, 15, 49]. The changesin the BAEP that occurred as a result of surgical manipulations of the brain-stem were found to be more consistent and occurred, on average, earlier thanchanges in cardiovascular signs could be detected [50]. Monitoring of BAEPsis therefore valuable in operations for large tumors of the acoustic nerve andother operations where the brainstem may be manipulated. When used inoperations on tumors of the acoustic nerve, the BAEP is elicited from the earopposite to the tumor. It is useful to consider the neural generators of the dif-ferent components of the BAEP [8, 51] when interpreting the recordingsbecause that can provide information about the anatomical location of thechanges.


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5 MAPPING THE FLOOR OF THE FOURTH VENTRICLE

Intraoperative mapping of the floor of the fourth ventricle can help the surgeonfind safe entry points to the brainstem for removal of intrinsic tumors or vascularmalformations. Mapping makes use of recordings of EMG responses from musclesthat are innervated by cranial nerves VII and XII while the floor of the fourth ven-tricle is being probed with a bipolar electrical stimulating electrode [52, 53] (Fig.13.6). This technique has mainly been able to identify the CN VII, but the locationof CN XII can also be determined. For the location of CN XII, recordings are madefrom the genioglossal muscle or from the tongue. Other locations can also be iden-tified using such mapping. Thus the location of the abducent and hypoglossal

FIGURE 13.6 Recordings of EMG potentials from muscles innervated by CN VII and CN XIIwhen bipolar electrical stimulation was done at different locations on the floor of the fourth ven-tricle. (A) Bipolar stimulation of the right facial colliculus and recordings from the genioglossal (CNXII) and orbicularis muscles (CN VII) on both sides. The stimulus current was 0.5 µA. (B) Bipolarstimulation at the left trigone of the hypoglossal (CN XII) nerve. (C) Bipolar stimulation of the leftfacial colliculus in the same patient who had a left peripheral facial paresis. The stimulus strengthrequired to evoke a response was 2 mA because of the facial paresis. Reprinted from [53].



nerves, the motor nucleus of the fifth cranial nerve, and the ambiguous nucleus canbe identified using these techniques [54] (see Chapter 15 for details).

6 MONITORING THAT CAN GUIDE THESURGEON DURING AN OPERATION

The use of electrophysiologic methods in the operating room can increase thesuccess rate and reduce failures in a few operations.

6.1 HEMIFACIAL SPASM

Neurophysiologic monitoring can increase the success rate of operations forhemifacial spasm (HFS) [55]. HFS is a rare disorder (incidence of approxi-mately 0.8 per 100,000 in the United States [56]) that can be cured by microvas-cular decompression (MVD) of the intracranial portion of the facial nerve. Inthis operation, a blood vessel is moved off the facial nerve and a soft implant isplaced between the vessel and the nerve. The basis for the neurophysiologicmonitoring is the finding that abnormal muscle responses that seem to be char-acteristic of HFS [57] disappear when the vessel that is associated with thespasm is moved off the facial nerve [8, 58] (Fig. 13.7). The abnormal muscle

FIGURE 13.7 EMG recordings from a patient undergoing MVD to relieve HFS. Each graph showsconsecutive recordings (beginning at top) from the mentalis muscle in response to electrical stim-ulation of the zygomatic branch of the facial nerve. As indicated, the recordings at the bottom ofthe left column were made when the vessel was lifted off the nerve. Reprinted from [58].


312 Aage R. Møller

response can be demonstrated by recording EMG potentials from a face musclewhile electrically stimulating a branch of the facial nerve different from thebranch that innervates the muscle from which recording is made (Fig. 13.8). Bymonitoring that response during an MVD operation for HFS, it is possible toidentify the vessel that causes the spasm [55]. That vessel may be an artery, avein, or a very small artery. Such monitoring has increased the success rate ofthe MVD operation, which, under ideal circumstances, can be more than 95%

FIGURE 13.8 Electrode placement for monitoring abnormal muscle response in a patient under-going MVD to relieve HFS. Reprinted from [8].



successful [55]. In some cases more than one vessel is in close contact with thefacial nerve. Before such intraoperative neurophysiological monitoring is intro-duced [55], some patients have to be reoperated on because vessels involved incausing the symptoms of HFS have remained in contact with the facial nerve.

6.2 MAPPING THE AUDITORY-VESTIBULAR NERVE

The auditory and the vestibular portions of the eighth cranial nerve are locatedclose together in the posterior fossa, and it is necessary to identify the cleavageplane between these two portions of the auditory vestibular nerve to performselective sectioning of the vestibular nerve. Although this can often be doneusing visual criteria, electrophysiological methods are of great help in this task[59].

Direct recording of sound-evoked CAPs from the surface of the eighth cranialnerve using a bipolar recording electrode is a useful method for identifying theborder between the auditory and the vestibular nerves. Bipolar recordings havea greater spatial selectivity than monopolar recordings and are the method ofchoice for this task. A hand-held bipolar electrode made of Teflon-insulatedsilver wires that are twisted and cut with an intertip distance of 1–2 mm [60] issuitable for probing the nerve (Fig. 13.9).

FIGURE 13.9 Bipolar electrode used to record from the exposed CN VIII. Reprinted from [60].


314 Aage R. Møller

When CN VIII is probed by a bipolar recording electrode, the response tosound stimulation is only present when the recording electrode is placed on theauditory nerve (Fig. 13.10). It has been shown that a low stimulus intensity isimportant for achieving the best spatial selectivity [59]. Recording from theexposed auditory-vestibular nerve using such a bipolar electrode requires cau-tion because it can injure the nerve.

6.3 MAPPING THE TRIGEMINAL NERVE

Mapping the intracranial portion of the sensory portion of the trigeminal nerveis useful in operations for selective posterior fossa trigeminal rhizotomy to treattrigeminal neuralgia. Similar techniques as already described for mapping CNVIII can be used to localize fibers of individual subdivisions of the trigeminalnerve as well as to ensure that the selective trigeminal rhizotomy is complete[61]. The intracranial portion of the trigeminal sensory nerve is mapped bystimulating the exposed trigeminal nerve electrically in the posterior fossa whilerecording the CAP from the individual branches of the trigeminal nerve wherethey emerge from their respective foramina. The recording electrodes are needleelectrodes (Grass-type E2 subdermal needles; Grass Instruments, Astro-Med,Inc., West Warwick, RI) placed in each of the supraorbital, infraorbital, andmental foramina. In some such operations, the respective reference electrodeswere placed subdermally 5 mm adjacent to the recording electrodes. Theantidromic CAPs were observed while the trigeminal nerve was stimulated

FIGURE 13.10 Bipolar recordings from the intracranial portion of CN VIII. The stimuli wereclicks with an intensity that was 25 dB above the threshold for BAEPs. Reprinted from [59].



electrically with a bipolar electrode similar to the one used for mapping theeighth cranial nerve (Fig. 13.11).

7 CONCLUSIONS

Many studies have shown that intraoperative monitoring of the integrity of thefacial nerve in operations for acoustic tumors is helpful in reducing the risk ofloss or impairment of facial function. Similar techniques can be used to moni-tor other cranial motor nerves, and such monitoring is an effective tool forreducing postoperative neurological deficits. Intraoperative neurophysiologicmonitoring also helps the surgeon in other ways, such as to confirm theanatomical location of specific structures, and it gives the surgeon a feeling ofsecurity that can make operating less stressful.

Mapping the floor of the fourth ventricle can benefit operations of the brain-stem by allowing the surgeon to find safe entry to the brainstem. Mapping theeighth cranial nerve is important for hearing preservation in operations for sec-tioning the vestibular portion in the cerebellopontine angle. Mapping the trigem-inal nerve can facilitate selective sectioning of branches of the trigeminal nerve.

FIGURE 13.11 Compound action potentials recorded from the trigeminal nerve by monopolarelectrodes placed in each of the three foramina. Reprinted from [61]. A: supraorbital foramen;B: infraorbital foramen; C: mental foramen.


316 Aage R. Møller

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C H A P T E R 14

Brainstem MappingNOBUHITO MOROTA

Department of Neurosurgery, National Children’s Medical Center, National Centerfor Child Health and Development, Tokyo, Japan

VEDRAN DELETIS


FRED J. EPSTEIN

Hyman-Newman Institute for Neurology and Neurosurgery, Beth Israel Medical Center, New York

1 Introduction1.1 What is Brainstem Mapping?

2 Methodology of BSM2.1 Anesthesia Regimen

3 Results of BSM4 Surgical Implications of BSM5 Clinical Limitations of BSM6 Representative Case of BSM7 Clinical Application of BSM8 SummaryReferences

ABSTRACT

Brainstem mapping is a neurophysiological method of locating the cranial nervemotor nuclei (CMN) on the floor of the fourth ventricle. The motor nuclei of the cra-nial nerves are usually located in the vicinity of specific anatomical landmarks on thefloor of the fourth ventricle. Because of the distorting effects of a tumor on the localanatomy, these landmarks are not evident in most patients. Even in patients withouta tumor, specific anatomical landmarks are often not visible. Different points of thesurgically exposed floor of the fourth ventricle were electrically stimulated by thesurgeon using a hand-held probe. Electromyographic responses were recorded withelectrodes inserted in the muscles of the head that are innervated by cranial motornerves. This technique was found to be useful for locating cranial nerve motor nucleibefore tumor resection and enabled the surgeon to avoid damaging the nuclei whenentering the brainstem. Furthermore, intraoperative neurophysiological localizationof the CMN showed specific patterns of displacement by brainstem tumors. Pontinetumors displaced the CMN of the nerve VII around the edge of the tumor, andmedullary tumors ventrally displaced the low CMN. Understanding the patterns of



320 Nobuhito Morota, Vedran Deletis, and Fred J. Epstein

CMN displacement can help in establishing a surgical plan that minimizes the riskof damaging the CMN and allows for safer surgery for brainstem tumors.

1 INTRODUCTION

Brainstem mapping (BSM) is emerging as an addition to the neurophysiologi-cal armamentarium available during surgery for brainstem lesions that oftenplaces cranial nerve motor nuclei (CMN) at risk for injury [1–4]. Historically,auditory brainstem responses (ABRs) and somatosensory evoked potentials(SEPs) were among the most commonly used neurophysiological techniquesfor monitoring during brainstem surgery [5]. However, responses obtainedfrom ABRs and SEPs give only indirect information regarding the functionalintegrity of the CMN. These two methods cover only 20% of the brainstem area[6] and thus play a limited role in the effort to preserve the functional integrityof the CMN during brainstem surgery.

1.1 WHAT IS BRAINSTEM MAPPING?

BSM is a neurophysiological technique that helps to localize the CMN on thesurgically exposed floor of the fourth ventricle (Fig. 14.1). During surgery fora brainstem tumor, the surgeon must know the location of the CMN to avoiddamaging this area.

Up to now, surgeons were guided by anatomical landmarks [7] in the operat-ing field of the fourth ventricle when trying to prevent injury to the CMN andother structures. Using these landmarks, safe entry zones to the brainstemthrough the floor of the fourth ventricle have been determined that include thesupra- and infrafacial triangles. Their anatomical importance has been dis-cussed elsewhere [8, 9]. The problems the surgeon encounters using anatomi-cal landmarks as guidelines for safe entry to the brainstem are twofold: first,normal anatomy is usually distorted by tumor, and second, anatomical land-marks on the floor of the fourth ventricle (facial colliculus and striaemedullares) can not be easily recognized in some patients with brainstemtumors. In our previous study [2], we showed that the facial colliculi could bevisualized in 3 out of 12 patients. This study was done in 7 patients withmedullary tumors that did not influence the anatomy of the facial colliculi andin 5 patients with a pontine tumor. In 9 out of 14 patients, the striae medullarescould be visualized (9 patients with medullary tumors and 5 patients with pon-tine tumors). BSM was used to localize the CMN and to provide the surgeonwith anatomical guidance, even when anatomical landmarks were not visible onfloor of the fourth ventricle [2, 3, 10, 11]. Thus, it provided guidance as to


FIGURE 14.1 Mapping of the brainstem cranial nerve motor nuclei. Upper left, drawing of the exposed floor of the fourth ventricle with the surgeon’shand-held stimulating probe in view. Upper middle, sites of insertion of wire hook electrodes for recording muscle responses. Far Upper right, compoundmuscle action potentials recorded from the orbicularis oculi and oris muscles after stimulation of the upper and lower facial nuclei (upper two traces) andfrom the pharyngeal wall and tongue muscles after stimulation of the motor nuclei of cranial nerves IX, X, and XII (lower two traces). Lower left, photo-graph obtained from the operating microscope showing the hand-held stimulating probe placed on the floor of the fourth ventricle (F). A: aqueduct. Mod-ified from [2].

321



where to make incisions on the floor of fourth ventricle and/or when to stoptumor resection at the bottom of the tumor cavity.

2 METHODOLOGY OF BSM

After endotracheal intubation, EMG wire recording electrodes were inserted intothe appropriate muscles under direct laryngoscopy. They were inserted bilater-ally into the posterior pharyngeal wall to record responses from the CMN IX andX and into the lateral aspect of the tongue to record the response of CMN XII.Wire electrodes were inserted into the obicularis oris and oculi muscles to recordresponses from CMN VII (Fig. 14.1). Electrodes can be safely placed in theextraocular muscles for mapping CMN III and CMN VI [12]. In this case, pairsof electrodes were used with an interelectrode distance of 5 mm. The recordingelectrodes were custom-made Teflon-coated wire electrodes (type 316SS 3T;Medwire, Mount Vernon, NY) with 2 mm bare, hooked tips. The electrode endwas encased in a 27-gauge needle, which allowed it to be manipulated with a longneedle holder. After insertion into the muscle, the needle was withdrawn, leav-ing the tip of the electrode in place. After surgical exposure of the floor of thefourth ventricle, electrical stimulation was delivered using a hand-held monopo-lar stimulation probe with a modified tip (Xomed, #82-25100; Medtronic XomedSurgical Products, Inc., Jacksonville, FL). A corkscrew electrode (Nicolet, Madi-son, WI), placed at FZ (10–20 International EEG System) was used as reference(anode). Stimuli of 0.2 ms duration were delivered at a stimulating rate of 4 Hzfor a few seconds. An initial stimulus intensity of 1.5–2.0 mA was used. Later,when muscle responses were obtained, the intensity was reduced to determinethe threshold (usually 0.3–2.0 mA). Mapping the upper and lower CMN tookabout 5 min. The EMG responses were recorded within an epoch length of 20 ms,were amplified 10,000 times, and were filtered between 50 and 2133 Hz.

2.1 ANESTHESIA REGIMEN

Anesthetics used for general anesthesia have little or no effect on the lowermotor neurons. Since we were stimulating the lower motor neurons (motornuclei of cranial nerves or their intramedullary roots), any type of anesthesiathat didn’t include a long-lasting relaxant was compatible with BSM.

In the first series of 18 patients, we used fentanyl, thiopental, and a short-acting, nondepolarizing relaxant. Anesthesia was maintained with fentanylinfusion, 0.4% isoflurane, and a 70% nitrous oxide and oxygen mixture. OnceBSM was established as a routine intraoperative procedure, our standard anes-thesia regimen included propofol, fentanyl, a nitrous oxide and oxygen mix-ture, and a short-acting muscle relaxant (prior to intubation only).


Brainstem Mapping 323

3 RESULTS OF BSM

In our study published previously [2], we neurophysiologically localized theCMN of the facial nerve prior to tumor resection in 8 out of 10 patients whounderwent surgery for brainstem tumors. The facial nucleus was typicallylocated close to the facial colliculus. CMN XII was often localized close to or atthe obex, and CMN IX or X was localized at the area rostral and lateral to theobex. Large pontine tumors displaced the facial nuclei laterally (at the edge ofthe tumor). Contrary to the mapping of the facial nuclei, localization of theCMN of IX or X and XII in patients with medullary tumors was not always pos-sible before tumor resection. The tumor mass displaced those nuclei ventrally,preventing electrical current from reaching the nuclei during stimulation.

Our data, collected in 20 patients with brainstem tumors and cervi-comedullary spinal cord tumors, showed displacement of the CMN in consis-tent patterns, depending on the location of the tumor (Fig. 14.2) [3]. Thosepatterns are as follows. In pontine tumors, the CMN of the facial nerves weredisplaced around the tumor edge on the floor of the fourth ventricle. An upperpontine tumor displaced the CMN of the facial nerve caudally, and a lower pon-tine tumor displaced them rostrally. If the tumor was predominantly occupy-ing one side, both facial nuclei were displaced to the opposite side. We did notfind displacement of the lower CMN in patients with pontine tumors and nodisplacement of the facial nuclei in patients with medullary tumors.

In patients with medullary tumors, one or more lower CMN were displacedventrally to the tumor. Therefore, mapping of lower CMN in those cases was onlypossible at the end of tumor resection at the bottom of the tumor cavity, andunsuccessful BSM of low CMN conveyed important information suggesting thatthe CMN could be located ventral to the tumor. In patients with cervi-comedullary spinal cord tumors, the lower CMN were displaced rostrally,sometimes involving the rostral displacement of the striae medullares [3]. Inpatients with small tumors, no displacement of the lower CMN was found.

The varying modality of tumor compression to the CMN based on tumorlocation seems to be derived from variations in tumor biology. It is well knownthat most pontine tumors are malignant and grow invasively in an intrinsicfashion, thus displacing the CMN VII bilaterally at the edge of the exposedtumor. On the other hand, the medullary tumor is likely to be low grade inmalignancy and tends to grow in a more exophytic fashion. As the tumorextends into the fourth ventricle, the lower CMN can be pushed ventrallybeneath it. The cervicomedullary junction spinal cord tumor behaves muchlike a medullary tumor. Since low-grade tumors are common at the cervi-comedullary junction, they displace the lower CMN rostrally during theirgrowth into the fourth ventricle [14]. Electrical stimulation of the floor of thefourth ventricle with a low stimulation rate and low current intensity is safe [2].



In a series of 18 patients, we have had 1 patient with transient, premature ven-tricle contraction during mapping of CN IX or X, and other patients have hada mild increase in blood pressure. Both of these side-effects disappeared afterthe stimulation ceased. Other authors [4, 15] have not reported any side effectsor complications during BSM. In an experimental animal study, Suzuki et al.[16] reported that transient hypotension and bradycardia developed in adultdogs when the floor of the fourth ventricle was electrically stimulated withgreater than 2 mA intensity. Respiratory arrest was observed with 3 mA. Theadministration of atropine sulfate prior to stimulation decreased the intensityof these side-effects.

FIGURE 14.2 Typical patterns of cranial nerve motor nuclei displacement by brainstem tumorsin different locations. Upper and lower pontine tumors typically push the facial nuclei around theedge of the tumor, suggesting that precise localization of the facial nuclei before tumor resection isnecessary to avoid their damage during surgery. Medullary tumors typically grow more exophyti-cally and compress the lower cranial nerve motor nuclei ventrally; these nuclei may be located onthe ventral edge of the tumor cavity. Because of the interposed tumor, in these cases mappingbefore tumor resection usually does not allow identification of cranial nerve IX, X, and XII motornuclei. However, responses could be obtained close to the end of the tumor resection, when mostof the tumoral tissue between the stimulating probe and the motor nuclei had been removed. Atthis point, repeated mapping is recommended because the risk of damaging motor nuclei is signi-ficantly higher than at the beginning of tumor debulking. Cervicomedullary junction spinal cordtumors simply push the lower cranial nerve motor nuclei rostrally when extending into the fourthventricle. Reprinted from [3].



4 SURGICAL IMPLICATIONS OF BSM

The surgical implications of BSM are important [3]. The pontine tumor oftenpushes the CMN VII around the tumor edge, suggesting that precise localiza-tion of the CMN VII before tumor resection is mandated to avoid direct damageby compression or incision on the floor of the fourth ventricle. The surgeon isrequired to perform an elaborate dissection at the tumor edge on the floor of thefourth ventricle where the CMN VII are in close proximity. If the tumor is inthe upper pons and the CMN VII are displaced caudally, incision on the floorof the fourth ventricle should be directed rostrally. If the tumor is in the lowerpons and the CMN VII are displaced rostrally, incision should be directed cau-dally (Fig. 14.3).

As mentioned previously, the medullary tumor tends to grow exophyticallyand compress some of the lower CMN ventrally. Care should be taken nearthe end of tumor resection if the CMN were unmapped before tumor resection.The unmapped lower CMN may be present at the bottom of the tumor cavity. Thetumor resection should be approached cautiously at the tumor base to preservethe lower CMN. Leaving a thin layer of tumor at the bottom of the tumor cavityis recommended, considering the fact that most medullary tumors are low grade(Fig. 14.4).

FIGURE 14.3 Schematic of the different displacements of the facial nuclei on the floor of thefourth ventricle in upper and lower pontine tumors. Arrows indicate the direction of the initial inci-sion on the floor of the fourth ventricle.



Large cervicomedullary junction spinal cord tumors often grow and extendinto the fourth ventricle. Displacing the lower CMN rostrally, the rostral end ofthe tumor may extend beneath the lower part of the floor of the fourth ventri-cle and lift it up slightly. In such a case, the surgeon needs to undermine thelower part of the floor of the fourth ventricle when the tumor resection reachesthe rostral end. If the rostral end of the tumor is directly approached throughthe floor of the fourth ventricle, the lower CMN are placed at high risk forinjury (Fig. 14.5).

FIGURE 14.4 Schematic of displacement of the lower CMN in patients with medullary tumors.Because the lower CMN are displaced ventrally, extreme care should be taken to prevent damag-ing them during resection of the tumor base.

FIGURE 14.5 Schematic of rostral displacement of the lower CMN by a cervicomedullary junc-tion spinal cord tumor. If the rostral end of the tumor is directly approached through the floor ofthe fourth ventricle, the lower CMN are placed at high risk for injury.



5 CLINICAL LIMITATIONS OF BSM

BSM has proven valuable for preventing direct damage to the CMN duringsurgery of brainstem tumors and other pathologies in and around the brainstem[2, 3, 6]. However, it does have some limitations.

First of all, this is a mapping technique, not a monitoring technique. BSM isa procedure to localize the CMN, and as such is performed intermittentlyduring tumor resection to confirm the location of the CMN. It is not a proce-dure to continuously monitor the integrity of the CMN throughout the tumorresection. Any damage induced during tumor resection cannot be prevented bythis method.

Second, BSM cannot detect damage to the corticonuclear tract originatingfrom the motor cortex and ending on the CMN. Therefore, supranuclear motorparalysis may occur even if the integrity of lower motor neurons is preserved(from the CMN to the cranial muscle).

Third, the response recorded at the end of the tumor resection does notmean that the CMN were preserved. Theoretically, the response could beobtainable from the cut end of the intramedullary roots of the cranial nerve thatwere mapped. However, this has not been our experience.

Furthermore, it seems very difficult to preserve other neural elementsinvolved in the swallowing and coughing reflex, despite the use of BSM. This isunderstandable, since BSM can only test the efferent part of those reflex arcs.Damage to the intramedullary afferent roots on neural connections betweennuclei is undetectable using this technique. Difficulties with swallowing orcoughing (with an absence of the gag reflex) may develop even though EMGresponses from the lower CMN have been maintained after BSM at the end oftumor resection.

Damage to the corticobulbar tract is a possible condition undetected byBSM. However, damage is less likely to happen because of the anatomy of thecorticobulbar tract. According to Krieg’s anatomy of the corticobulbar tract[17], there are seven major branches of the corticobulbar tract. All of themrun in the ventrodorsal direction toward the CMN (Fig. 14.6). Thus, as longas the brainstem tumor is approached through the floor of the fourth ventri-cle, the corticobulbar tract remains relatively isolated from possible trauma.Furthermore, because of the complexity of CMN innervation by the corti-cobulbar tract, it would be unlikely that all branches of the corticobulbar tractending up on the CMN would be damaged at once. Although there is a pos-sibility that some branches of the corticobulbar tract could be damagedduring surgery, their function will be taken over by other corticobulbar tractslater. Permanent damage to the corticobulbar tract by brainstem surgeryseems exceptional as long as the brainstem lesion is approached from thefourth ventricle.



6 REPRESENTATIVE CASE OF BSM

The advantages and limitations of using BSM during surgery on a brainstemlesion when anatomy is distorted are described in the following case (patient 1).A 54-year-old woman had repeated episodes of brainstem hemorrhage result-ing in mild left hemiparesis, sensory disturbance, dysarthria, and bilateral facialweakness (House & Brackmann grade 2). MRI revealed a large brainstemhematoma caused by a brainstem cavernous angioma (Fig. 14.7). Duringsurgery, swelling of the right upper half of the floor of the fourth ventricle wasso prominent that the left upper half of the floor was not visible (Fig. 14.8). Noanatomical landmarks were observed on the upper half of the floor of the fourthventricle. The striae medullares were displaced caudally. An abnormal vesselwas observed on the swelled right upper part of the floor of the fourth ventri-cle. A part of the hematoma was exposed rostral to the abnormal vessel. Byusing BSM, we located the right facial colliculus caudal to the abnormal vessel(Fig. 14.9). An incision on the floor of the fourth ventricle was directed caudallyfrom the exposed hematoma and rostral to the abnormal vessel (Fig. 14.10).The hematoma and cavernous angioma were extensively removed (Fig. 14.11).BSM following the hematoma removal was consistent with responses obtainedprior to hematoma removal. Postoperatively, the patient showed no neurological

FIGURE 14.6 Schematic of three major branches of the corticobulbar tract (midbrain, pontine,and medullary; drawn according to Krieg’s anatomy book), with their divisions (a–g). Note that thecorticobulbar tract innervates the cranial nerve motor nuclei from the ventral side. Therefore, it isless likely that they will be damaged during surgery for brainstem tumors.


FIGURE 14.7 Preoperative MRI of patient 1. A large hematoma caused by a cavernous angioma occupies the pons predominantly on the right side.

329


FIGURE 14.8 Left, intraoperative photograph of patient 1. The right pontine part of the floor of the ventricle bulges onto the left side. Abnormal ves-sels cross the right part of the pontine floor of the fourth ventricle. Part of the hematoma is exposed rostrally to the abnormal vessel. Right, intraoperativephotograph of BSM using a hand-held stimulating probe.

330



deterioration except mild ataxia. Facial weakness disappeared soon after thesurgery (Fig. 14.12).

This example illustrates how BSM can show the surgeon where to performthe initial incision and prevent injury to the CMN of the facial nerves.

7 CLINICAL APPLICATION OF BSM

The methodology of BSM can be applied to locate CMN other than CMN VII,IX or X, and XII. Mapping of the oculomotor nuclei (CMN III) and trochlearnuclei (CMN IV) can be achieved in surgery on a midbrain lesion if it isapproached dorsally. The same is true in surgery for quadrigeminal plate, tectal,and pineal region tumors [12].

FIGURE 14.9 Results of BSM from patient 1. The largest response from the right orbicularis oculiand oris was recorded from the area caudal to the abnormal vessel (B). The amplitude of theresponse is smaller rostral (A) and caudal (C) to the point where the maximum response wasobtained.



8 SUMMARY

Recent advances in neurophysiological techniques have influenced several chal-lenging neurosurgical procedures [18]. Despite the advent of microneuro-surgery and MRI, which clearly depicts the relationship between the surgicallesion and the surrounding anatomy [8, 19–22], surgery on the brainstem stillholds the possibility of surgical morbidity, mainly because of the distortingeffects that a tumor can have on the local anatomy. The neurophysiologicaltechnique of BSM can be used to recognize the functional anatomy of the CMNwhen this anatomy has been distorted.

Mapping critical neural structures during surgery has become an importantconcept in intraoperative neurophysiology. Brainstem lesions in the midbrain,pons, and medulla can now be surgically resected using BSM as a technique tolocate the CMN on the floor of the fourth ventricle. Using BSM, the surgeon isguided to enter the brainstem through a “silent area,” thus avoiding directdamage to the CMN.

FIGURE 14.10 Left, schematic of results of BSM from patient 1. Right, localized area of the rightfacial nucleus is superimposed on the floor of the ventricle. Surrounding grey zone indicates thearea where smaller responses from the facial muscles were obtained by BSM. No response wasobtained from the area rostral to the abnormal vessel. Based on the result of BSM, an incision wasmade on the hematoma cranial to the abnormal vessel. Rt FN: right facial nucleus.


FIGURE 14.11 Left, CT scan taken immediately after surgery demonstrated the path of hematoma removal. Right, MRI taken 2 weeks after surgeryshowed a small residual hematoma with sufficient brainstem decompression.

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REFERENCES

1. Katsuta, T., Morioka, T., Fujii, K., and Fukui, M. (1993). Physiological localization of the facialcolliculus during direct surgery on an intrinsic brain stem lesion. Neurosurgery, 32, 861–863.

2. Morota, N., Deletis, V., Epstein, F.J., Kofler, M., Abbott, R., Lee, M., and Ruskin, K. (1995).Brain stem mapping: Neurophysiological localization of motor nuclei on the floor of the fourthventricle. Neurosurgery, 37, 922–930.

3. Morota, N., Deletis, V., Lee, M., and Epstein, F.J (1996). Functional anatomic relationshipbetween brain stem tumors and cranial motor nuclei. Neurosurgery, 39, 787–794.

4. Strauss, C., Romstock, J., Nimsky, C., and Fahlbusch, R. (1993). Intraoperative identificationof motor areas of the rhomboid fossa using direct stimulation. J. Neurosurg., 79, 393–399.

5. Albright, A.L., and Sclabassi, R.J. (1985). Use of the Cavitron ultrasonic surgical aspirator andevoked potentials for the treatment of thalamic and brain stem tumors in children. Neuro-surgery, 17, 564–568.

6. Fahlbusch, R., and Strauss, C. (1991). The surgical significance of brainstem cavernous heman-giomas. Zentrabl. Neurochir., 52, 25–32.

7. Lang, J., Ohmachi, N., and Lang Sen, J. (1991). Anatomical landmarks of the rhomboid fossa(floor of the 4th ventricle), its length and its width. Acta Neurochir. (Wien), 113, 84–90.

8. Bricolo, A., and Turazzi, S. (1995). Surgery for gliomas and other mass lesions of the brainstem.In “Advances in Technical Standards Neurosurgery, 22” (L. Symon, ed.), pp. 261–341.Springer, New York.

9. Kyoshima, K., Kobayashi, S., Gibo, H., and Kuroyanagi, T. (1993). A study of safe entry zonesvia the floor of the fourth ventricle for brain-stem lesions: Report of three cases. J. Neurosurg.,78, 987–993.

10. Grabb, P.A., Albright, A.L., Sclabassi, R.J., and Pollack, I.F. (1997). Continuous intraoperativeelectromyographic monitoring of cranial nerves during resection of fourth ventricular tumorsin children. J. Neurosurg., 86, 1–4.

FIGURE 14.12 Postoperative facial appearance of patient 1 showed complete recovery from facialweakness.



11. Strauss, C., Romstock, J., and Fahlbusch, R. (1999). Pericollicular approaches to the rhomboidfossa: Part II. Neurophysiological basis. J. Neurosurg., 91, 768–775.

12. Sekiya, T., Hatayama, T., Shimamura, N., and Suzuki, S. (2000). Intraoperative electrophysio-logical monitoring of oculomotor nuclei and their intramedullary tracts during midbrain tumorsurgery. Neurosurgery, 47, 1170–1177.

13. Epstein F.J., and Farmer, J.P. (1993). Brain-stem glioma growth patterns. J. Neurosurg., 78,408–412.

14. Epstein, F., and Constantini, S. (1996). Practical decisions in the treatment of pediatric brainstem tumors. Pediatr. Neurosurg., 24, 24–34.

15. Eisner, W., Schmid, U.D., Reulen, H.J., Oeckler, R., Olteanu-Nerbe, V., Call, C., and Kothbauer,K. (1995). The mapping and continuous monitoring of the intrinsic motor nuclei during brainstem surgery. Neurosurgery, 37, 255–265.

16. Suzuki, K., Matsumoto, M., Ohta, M., Sasaki, T., and Kodama, N. (1997). Experimental studyfor identification of the facial colliculus using electromyography and antidromic evoked poten-tials. Neurosurgery, 41, 1130–1136.

17. Krieg, W.J.S. (1957). “Brain mechanisms in diachrome,” Brain Books, 2nd edition, pp. 287–290.Bloomington, IL.

18. Deletis, V. (1993). Intraoperative monitoring of the functional integrity of the motor path-ways. In “Electrical and magnetic stimulation of the brain and spinal cord.” (O. Devinsky, A.Beric, M. Dogali, eds.), pp. 201–214. Raven Press, New York.

19. Abbott, R., Shiminski-Maher, T., and Epstein, F.J. (1996). Intrinsic tumor of the medulla: Pre-dicting outcome after surgery. Pediatr. Neurosurg., 25, 41–44.

20. Epstein, F., and McCleary, E.L. (1986). Intrinsic brain stem tumors of childhood: Surgicalindications. J. Neurosurg., 64, 11–15.

21. Pierre-Kahn, A., Hirsch, J.F., Vinchon, M., Payan, C., Sainte-Rose, C., Renier, D., Lelouch-Tubiana, A., and Fermanian, J. (1993). Surgical management of brain stem tumors in children:Results and statistical analysis of 75 cases. J. Neurosurg., 79, 845–852.

22. Pollack, I.F., Hoffman, H.J., Humphreys, R.P., and Becker, L. (1993). The long-term outcomeafter surgical treatment of dorsally exophytic brain stem gliomas. J. Neurosurg., 78, 859–863.


C H A P T E R 15

IntraoperativeNeurophysiologicalMapping and Monitoringfor SupratentorialProceduresGEORG NEULOH AND JOHANNES SCHRAMM

Department of Neurosurgery, University of Bonn, Germany

1 Introduction2 Somatosensory Evoked Potentials

2.1 Technique2.2 Principles of Clinical Application

3 Intraoperative and Perioperative NeurophysiologicalFunctional Mapping3.1 SEP Phase Reversal3.2 Extraoperative Mapping with Grid or Multiple-

Strip Electrodes for Motor, Sensory,and Speech Localization

3.3 Intraoperative Electrical Stimulation of MotorCortex and White Matter

3.4 MEP Mapping4 MEP Monitoring

4.1 Technique4.2 Principles of Clinical Application

5 Safety and Anesthesia5.1 Safety5.2 Anesthesia

6 Value and Limitations from a Clinical Perspective6.1 Aneurysms6.2 Aneurysms—Summary



340 Georg Neuloh and Johannes Schramm

6.3 AVMs—Summary6.4 Centrally Located Tumors6.5 Centrally Located Tumors—Summary

AcknowledgmentsReferences

ABSTRACT

The goal of delineation through mapping and monitoring of eloquent cortical areas andsubcortical pathways is to achieve a more radical cytoreduction while still preservingunimpaired function. The use of different neurophysiological methods in the operationroom has a long history, but monitoring with evoked potential technology is a devel-opment of the last 25 years; in particular, motor tract monitoring is a very recent devel-opment. In this chapter we summarize the experience from our center in intraoperativeneurophysiological monitoring of more than 1500 patients over the last 10 years. Thisincludes patients operated on for cerebral aneurysms, arteriovenous malformations,central and insular tumors, and deep-seated cerebral lesions, as well as patients whohave undergone surgery for epilepsy. The methods employed for monitoring weresomatosensory evoked potential phase reversal; motor pathway monitoring; mappingof motor, sensory, and speech areas; and zones of ictal and interictal spiking in patientswith chronic epilepsy. The experience in monitoring supratentorial lesions includesover 60 vascular malformations, 170 tumors, and over 200 patients with epilepsy. Wediscuss the interpretation of results, safety and anesthesia issues, and the limitationsand drawbacks of the method. Intraoperative neurophysiological monitoring of thefunctional integrity of the cortical sensory and motor areas and pathways is noninva-sive and does not interfere with the ongoing surgical procedure. It gives immediatefeedback about functional impairment of the monitored structure. In some cases, thisfeedback provides the opportunity to rectify this impairment.

1 INTRODUCTION

From the end of the 1970s to the middle of the 1980s, intraoperative evokedpotential monitoring developed from an experimental technique into a reliabletool used during different types of cranial and spinal surgeries involvingacoustic, motor, and sensory evoked potential modalities. The intraoperativeuse of neurophysiological methods, in particular evoked potentials as a moni-toring tool, was independently conceived by a Japanese orthopedic surgeon [1]and a group of American neurosurgeons [2]. The idea to use evoked potentialmonitoring was first applied to spine surgery and later on to posterior fossasurgery. The first papers about evoked potentials from our group concernedexperimental spinal cord injury, but clinical applications soon followed [3–8].Some of the early diagnostic applications for spinal lesions thought to be impor-tant were soon overshadowed by the advent of MRI technology, which is moreproficient for pinpointing intramedullary lesions (e.g., in multiple sclerosis[9]). The early years were devoted to working out the technical principles and


Intraoperative Neurophysiological Mapping and Monitoring 341

optimizing anesthesia, electrode montages, and criteria of abnormality. One ofthe first meetings on intraoperative monitoring was an informal one in St. Louisin 1977. This was followed shortly afterwards by the First International SpinalCord Monitoring Symposium held in Tokyo and organized by T. Tamaki [10].Some of the historical views discussed are quite interesting in retrospect, suchas the definition of criteria for abnormal intraoperative changes in evokedpotentials. Although these criteria were arbitrarily defined, they were based ona lengthy experience of observing SEPs vary and change during surgery, some-times being lost and sometimes recovering again. These criteria were tentativelybased on experiences that were not scientifically justified or on statisticallyexamined series that used varying parameters. Twenty years later, much of whatwas intuitively defined in those days has remained valid:

1. Changes in amplitudes are much more variable than latency changes.2. Amplitude changes have to be much more significant than latency

changes to be relevant. 3. Waveform alterations are not really important, with a few exceptions.

When the first papers on intraoperative monitoring were presented, skepticsasked questions such as the following: What are you going to do when thepotential is lost? Are you going to leave the tumor in? This last question hassince been answered. A surgeon’s reaction may involve checking retractors, ves-sels, clips, and blood pressure; stopping coagulation; applying papaverine; stop-ping dissection; and changing the area and style of dissection. In short, monitoringhas become an educational tool. Evoked potential monitoring during surgery,first with somatosensory evoked potentials (SEPs) and now also with motorevoked potentials (MEPs), has become an accepted technique for monitoring theintegrity of motor and sensory pathways within the spinal cord, the medulla, thebrainstem, and the brain.

For many years MEPs could not be reliably assessed intraoperatively. Manyof the so-called false-positive and false-negative results of the past, when SEPmonitoring was the only available methodology (particular during aneurysmsurgery) [11–16], can now be judged using both modalities. It has become quiteclear that monitoring using SEPs, MEPs, and auditory evoked potentials (AEPs)improves safety standards for intracranial surgery. Certain lesions, such as largemultilobulated aneurysms in the anterior cerebral circulation, should not beoperated on without neurophysiological monitoring. Monitoring reassures thesurgeon when MEPs and SEPs remain stable with a clipped internal carotidartery (ICA), and it clarifies necessary action if potentials are lost with a clip onthe ICA. There are many other instances in which monitoring has provenextremely useful. In our hospital service, certain procedures, such as treatmentof central and insular gliomas, acoustic neurinomas with preserved hearing,complex aneurysms, and central arteriovenous malformations (AVMs), would



not be done without monitoring. This chapter reviews our current experienceusing intraoperative neuromonitoring techniques during surgeries for supra-tentorial lesions.

2 SOMATOSENSORY EVOKED POTENTIALS

SEP recording has become a well-established method in intraoperative neu-romonitoring. Extensive literature exists on SEP monitoring during spinal cordand posterior fossa surgeries for the following services: neurosurgery [4, 5, 7,8, 17–26], orthopedic surgery [27, 28], cardiovascular surgery [29–31], andinterventional neuroradiology [32]. SEP monitoring with supratentorial proce-dures is mainly applied for functional mapping purposes with lesions adjacentto the central region (see Section 3) and for continuous monitoring purposesin aneurysm surgery [11, 15, 16, 33–40]. The latter application has becomestandard in a growing number of neurosurgical centers over the last decade. Itis based on the well-established observation of a close relationship between cor-tical cerebral blood flow and SEP changes [41–44]. With aneurysm dissectionand clipping, SEPs may reflect intentional or inadvertent vessel occlusion orcompromise. In addition, clinical experience and experimental work haveshown that SEPs are sensitive to local factors such as pressure or heat, as wellas to systemic parameters like blood pressure, body temperature, or metabolicchanges. They may therefore also be applied with other lesions, such as vascu-lar malformations or tumors. This chapter sketches SEP stimulation and record-ing techniques, safety and anesthesia requirements, and principles and specificaspects of their clinical application as appears necessary for understanding SEPmonitoring in supratentorial surgical procedures.

2.1 TECHNIQUE

For intraoperative monitoring purposes, SEPs are elicited and recorded accord-ing to common international standards previously published [7, 15–17, 45, 46].A comprehensive review of the underlying functional neuroanatomy and phys-iology as well as detailed considerations regarding SEP stimulation and record-ing in the neurosurgical setting can be found in Intraoperative NeurophysiologicMonitoring by A. Møller [26]. Here we will present the basic technical and phys-iological information. The basic principle behind SEP recording is stimulationof a peripheral nerve with recording of the resulting evoked activity from thecentral nervous system, which typically arises from nuclei of the somatosensorypathways, the cortex, and the axonal fibers [26]. In neuromonitoring of supra-tentorial lesions, cortical activity must obviously be included in the recording



scheme, although subcortically evoked SEP components may give valuableadditional information.

2.1.1 Stimulation

SEPs are typically elicited by electrical bipolar stimulation of a peripheral nerve[46]. The most commonly stimulated nerves are the median nerve, if sensorymodalities and cortical regions representing the upper extremities are to be mon-itored, and the posterior tibial nerve for the lower extremities. SEP recordingfrom these nerves is easiest to obtain and provides the most stable results [23].Under special circumstances, such as amputated limbs or preexisting nervedamage, other (e.g., ulnar or peroneal) nerves may be chosen for stimulation.

The cathode is placed proximally to avoid anode block of the ascendingaction potential. Monopolar pulses of 200 to 500 µs duration are delivered asconstant-current or constant-voltage stimuli through sterile subcutaneous needleelectrodes or surface electrodes spaced about 2 cm apart. We prefer needle elec-trodes for the posterior tibial nerve and surface electrodes for median nerve stim-ulation. Ground electrodes (saline-soaked cloth wrapped around the stimulatedlimb) are placed close to the stimulation site to keep the stimulating artifactlow. With simultaneous stimulation of several limbs, which is often the casein intraoperative monitoring, a single ground must be used. The actual stim-ulation parameters (such as frequency and intensity) need to be adjusted tointraoperative requirements, particularly regarding to the effects of generalanesthesia.

2.1.1.1 Stimulus Intensity

As with awake patients, the stimulus intensity is set slightly above the motorthreshold in nonrelaxed patients. Otherwise, the lowest intensity at which themaximum amplitude of early SEP components can be evoked is chosen. It maybe considerably higher in anesthetized than in awake patients, but 20–25 mAwith median nerve stimulation and 25–30 mA with posterior tibial nerve stim-ulation are rarely exceeded (Table 15.1). Unnecessarily strong stimulation mustbe avoided, both for safety considerations and to maintain minimal muscletwitching in nonrelaxed patients, which can be disturbing during subtle micro-surgical supratentorial procedures.

2.1.1.2 Stimulus Duration

A stimulus duration of 300 µs is usually sufficient, representing a compromisebetween safety considerations and the effort to obtain a stable signal. In cases ofdifficult SEP recording (e.g., with sensory polyneuropathy), a stimulus durationof 500 µs or more may be adequate.



2.1.1.3 Stimulus Frequency

SEP recording requires the averaging of 200–500 (or more) trials. Thus stim-ulation must be repeated at a relatively fast frequency. Stimulation frequenciesof 1–10 Hz are commonly used in awake patients. With intraoperative moni-toring, a fast SEP update is obviously important in order to provide real-timefeedback and to allow for early reaction to relevant changes. No significant dif-ferences in latency and amplitude occur with stimulation frequencies between1 and 3 Hz, and a stimulus frequency below 5 Hz has been recommended forroutine recording of early cortical SEPs [46]. In our experience, a stimulationfrequency around 5 Hz (e.g., 5.3 Hz) represents a good trade-off between a fastupdate and high-amplitude, stable potentials. Stimulation at exactly 5 Hz maylead to interference with line-frequency (50 or 60 Hz) artifacts, which wouldbe particularly disturbing since 50 or 60 Hz notch filters should not be appliedwith a recording of early SEP components (see Section 2.1.2). In general, aneven-numbered Hz value, or harmonic parts of 50 or 60 Hz, should be avoidedto minimize artifacts. If SEPs are recorded bilaterally, stimulation may be per-formed by alternating between sides to preserve update speed. With such astimulus rate, and particularly in combination with a current anesthetic regi-men, an SEP update up to three times per minute or even more frequently maybe obtained, which comes close to real-time monitoring [47] (Fig. 15.1).

2.1.2 Recording

2.1.2.1 Electrode Montage

For intracranial procedures, the recording electrode montage should includea cervical and a cortical site to differentiate between central and peripheral causesof SEP latency changes. This setup also helps in differentiating technical problems

TABLE 15.1 SEP Stimulation and Recording Parameters for IntraoperativeMonitoring of SEPs

Median nerve Tibial nerve

Pulse width 300 (200–500) µs 300 (200–500) µs

Intensity max. 20–25 mA max. 25–30 mA

Stimulation rate 5.3 Hz 5.3 Hz

Recording sites C3′, C4′ (C5) vs Fpz Cz (lower cervical) vs Fpz

Sweep length 50 ms post stim 100 ms post stim

Averages 150–250 150–250

Band pass 30–3000 (500) Hz 30–3000 (500) Hz



from relevant changes that may occur intraoperatively. The cervical electrodeshould be placed at about C5–C7 spine level, whereas the scalp electrodes forrecording of cortical potentials are placed at parietal positions 2–3 cm posteriorto the C3–C4 (upper extremity) or the Cz (lower extremity) sites of the Inter-national 10–20 System. Recording is performed in a referential way with the ref-erence electrode placed at Fpz, although other montages are also used (e.g.,with extracranial references) [26, 46, 48]. Since intraoperative recording ofspinal components of SEPs may often prove difficult (in particular with lowerextremity SEPs) and acute peripheral changes are unlikely to occur, scalp elec-trodes alone can be considered sufficient in many cases (see Section 2.2.1). Theskin incision for craniotomy may necessitate some adjustment of electrodeplacement, although this problem is more common with MEP recording, sinceSEPs are usually monitored in cases requiring standard frontotemporal cran-iotomy, e.g., in cerebral aneurysms. Intraoperative SEP recording is best per-formed through sterile subdermal needle electrodes. It is recommended to placeat least two electrodes at each recording site—one as a reserve—since elec-trodes may easily slip during the disinfection and scrub procedure. Impedancemeasured at 100–500 Hz should be kept below 5–10 kΩ.

FIGURE 15.1 Fast median nerve SEP updates were recorded in a patient under propofol anesthe-sia. Twenty updates were obtained within 7 minutes, allowing for nearly real-time monitoring.



2.1.2.2 Filtering

The signal is amplified and (digitally) filtered. A band-pass of about 10–3000Hz is standard in common outpatient SEP recording [46], and equivalent fil-tering parameters are usually applied with intraoperative recording. However,the signal components most relevant for intraoperative purposes, namely, thespinal and the early cortical responses, do not have much power above 100–200 Hz. Therefore, a considerably tighter low-pass filter can usually be appliedwithout losing much relevant information. High-frequency artifacts are commonin the operating room setting and may require aggressive filtering in order toenhance the signal-to-noise ratio. According to our experience, low-pass filter-ing as low as 500 Hz or even lower can be used without significant compromiseof early cortical SEP recording. On the other hand, very tight high-pass filter-ing should not be used and will rarely be necessary above 30 Hz. Line-frequencynotch filters, available with most current recording systems, should not beapplied or applied only in cases with a severe artifact problem, since the signalof interest has its main power within this frequency range. Ringing, an artifactcaused by the filter, may also occur.

2.1.2.3 Sweep Length and Averaging

A poststimulus time window of 50–100 ms with median or tibial nerve stim-ulation is usually sufficient to register the relevant early SEP components. Thenumber of sweeps averaged depends on the signal-to-noise ratio, which can bequite low intraoperatively because of the usually high noise level and the oftenlow SEP amplitude under general anesthesia. With an adequate anesthetic reg-imen and with properly chosen stimulation and recording parameters, aver-aging of 100–150 sweeps or even fewer is sufficient in many cases [47]. Inintraoperative situations requiring a particularly fast update, the averaging pro-cedure can be stopped manually as soon as an assessable potential can be rec-ognized. The amplitude gain through this method (the averaging procedureleads to a slight amplitude reduction due to the natural latency jitter of thesignal) will be insignificant in most cases.

2.1.2.4 Signal

A large variety of positive and negative deflections can be recorded fromnumerous spinal and cranial recording sites with peripheral nerve stimulation[26, 49]. However, for intraoperative monitoring purposes, only a few SEPcomponents are relevant and can be reliably assessed. If spinal components canbe obtained, the most prominent negative deflections in healthy subjects occurat approximately 13 ms (N13; upper extremity SEP) and 30 ms (N30; lowerextremity SEP) after the stimulus . For median nerve SEPs, they most probably



represent dorsal horn postsynaptic activity triggered by ascending volleys fromthe dorsal nerve roots, which are reflected by smaller positive deflections pre-ceding the N13/22 [49]. The N30 recordable at C5–C7 vs. Fpz with tibial nervestimulation probably arises at the pontomedullary junction. The SEP compo-nents most commonly evaluated intraoperatively are the early cortical compo-nents N20 (upper extremity SEP) and P40 (lower extremity SEP), which arerecorded from the (contralateral) parietal postrolandic electrode positiondescribed previously. They probably correspond to activity elicited in the pos-terior bank of the central sulcus (Brodmann area 3b) and are followed byP25/N50-components, which are thought to be generated in Brodmann areas 1and possibly 3a/4 [50, 51].

Later components are probably generated in secondary association cortices.There is little experience with those late potentials in the intraoperative setting,in particular since they are more sensitive to anesthetic effects. They are not rou-tinely evaluated for intraoperative monitoring purposes. Earlier componentsimmediately preceding the N20/P40 may arise from subcortical structures like thebasal ganglia and could therefore be of particular interest with supratentorial pro-cedures [52], but they are too small and delicate to allow for reliable intraopera-tive evaluation. With all SEP components, amplitude and latency are the mostimportant parameters that can be easily and objectively evaluated, the potentialshape being more difficult to assess. Latencies are usually determined from stim-ulus to potential peak or between potential peaks (e.g., N13/N30–N20/P40 forcentral conduction time; for a definition of central conduction time, see [42]), andamplitudes are measured in a base-to-peak or peak-to-peak fashion. Common cri-teria for assessing SEP parameters intraoperatively are discussed in following text.Table 15.1 summarizes common stimulation and recording parameters.

2.2 PRINCIPLES OF CLINICAL APPLICATION

SEP monitoring can obviously only provide direct information about thesomatosensory pathways and regions. However, indirect conclusions aboutother brain regions can be drawn from SEP observation. Several different prin-ciples apply. Local proximity (e.g., of central lesions) makes it possible thatlocally interfering factors affect both the target region and adjacent somatosen-sory structures. Adjacent or remote regions sharing a common vascular supplywith somatosensory structures can be indirectly assessed with vascular proce-dures (e.g., in middle cerebral artery [MCA] aneurysm surgery). Here theM2/M3 branches may supply the motor and sensory cortex simultaneously, andthus SEP changes would also indicate some possibility of a major motor deficit.Smaller perforators will more likely affect only one tract system. Therefore, ifperforator manipulation is likely to occur [e.g., large posterior communicating



artery (PCOM) or ICA bifurcation aneurysm], combined SEP and MEP moni-toring is advisable.

SEP monitoring may also reflect the general functional state of the brain andcan give important information in case of increasing intracranial pressure causedby remote events (bleeding), general hypoxia, or other systemic changes. Thisfact is most important when trying to determine the prognosis for comatosepatients on the neurosurgical intensive care unit [53–56], but it may also be ofuse intraoperatively. With every application, only clinical experience can revealthe validity of SEP findings, i.e., the degree to which SEP changes reflect sig-nificant physiological phenomena in the target structure.

2.2.1 Interpretation and Practical Aspects

The relevant parameters and SEP components have been described (Section2.1.2). At present, there is no definite criterion for when to consider SEPchanges significant with regard to impending neural impairment. Normal fluc-tuations, technical conditions, the influence of systemic factors like anesthesiaor blood pressure (Fig. 15.2), and interindividual differences must be takeninto consideration when interpreting intraoperative SEP findings.

FIGURE 15.2 Effect of systemic blood pressure on SEP. Median nerve SEPs were recorded duringdissection of a right temporobasal AVM. During bleeding from the AVM, mean arterial blood pres-sure (ABP) was lowered to 60 mmHg for more than 1 hr, eventually leading to a significant impair-ment of SEP amplitude. This was resolved when ABP was raised above 80 mmHg after the successfulresection of the AVM.



Although they still remain arbitrary to a certain extent, the experimental andclinical literature converges toward some criteria concerning SEP interpreta-tion. A latency increase of earlier components by 10% is usually considered sig-nificant, and an amplitude decrease by less than 30–50% is considered withinnormal range [11, 15, 33, 34, 36–42, 57]. It is worthwhile to check suddendrops of amplitude against recent anesthetic bolus, blood pressure decreases, orsurgical maneuvers. Changes of SEP waveforms are much more difficult toassess objectively and have been found to be of little value.

SEP changes must be determined by comparing the latest curve with somereasonable baseline measurement. Usually, a first baseline potential is obtainedafter induction of anesthesia, before the operation has started. However, cran-iotomy and opening of the dura may lead to marked SEP changes before the rel-evant intracranial procedure has started. Thus it is often necessary to update thebaseline values. These postdurotomy changes may be due to brain prolapsewith ischemia at the rim or air between cortex and skull [58]. Moreover, non-surgical factors like fluctuation of anesthesia, change in technical conditions, orprevious transient or incomplete neural impairment may also lead to intraop-erative SEP changes. These must be differentiated from truly current patho-logic events so that further relevant changes can be interpreted with regard tothe latest state considered stable.

In principle, SEP monitoring makes sense with virtually all supratentorialprocedures with regard to possible systemic or remote events, even if thesomatosensory system is not affected. Given limits on time, equipment, and staff,a more specific use of SEP monitoring appears desirable. The next section pre-sents some considerations on how to use a simple yet sensitive setup with spe-cific applications. A general aspect to consider is whether to record SEPsbilaterally. In principle, bilateral recording is useful even with a clearly lateral-ized lesion, since monitoring of the unaffected side provides a biological control,which helps to differentiate specific (i.e., localized technical or iatrogenic) fromsystemic effects (e.g., anesthetic). In midline lesions such as anterior communi-cating artery (ACOM) aneurysms, the necessity of bilateral recording is obvious.

Another issue is whether to record more than cortically evoked responses.Many published results refer to the central conduction time (CCT) [11, 15, 33,34, 36–40]. In order to determine CCT, cervical potentials need to be recordedas well. The presence of spinal potentials also helps to ensure that proper stim-ulation and conduction through the peripheral nerves are being maintained.This helps to distinguish between peripheral failure and central failure whenchanges in cortical SEPs occur. We have seen two cases with unilateral corticaland spinal SEP loss due to acute plexus traction from an unnoticed droppedarm in the sitting position. However, in the operating room these subcorticalpotentials may be very difficult to record, much more so than cortical activity,in particular with tibial nerve stimulation. In fact, reliable recording of cervicalpotentials cannot be obtained in many cases.



2.2.2 Specific Applications

2.2.2.1 Aneurysms

In supratentorial surgery, continuous SEP monitoring is mainly used with cere-bral aneurysms [11, 15, 16, 33–40]. The primary goal of recording SEPs is todetect impairment of cortical perfusion by intended or inadvertent vessel occlu-sion. SEP changes are expected to also reflect perfusion of nonsensory eloquentareas like the motor or speech cortex, as well as local events (pressure or trac-tion from retractor) and systemic influences. This necessitates that the manipu-lation of larger arteries is monitored (i.e., of ICA, M1, or A1). Principally, SEPmonitoring in supratentorial aneurysms is only reliably used with lesions of theanterior circulation. The territory supplied by the posterior cerebral artery isneither overlapping with, nor adjacent to, the somatosensory cortex. The situa-tion is different with posterior fossa aneurysms, since vascular supply of infraten-torial pathways stems from the basilar and vertebral arteries. Tables 15.2 and15.3 summarize the correlation of SEPs, surgical events, and clinical outcome.

TABLE 15.3 SEP Findings versus Clinical Outcome with Temporary Vessel Occlusionin Aneurysm Surgerya

Vessel occlusion (46/148) SEP change (18/46) No SEP change (28/46)

Clinical impairment (8) 6/18 (33%) 2/28 (7%)

No clinical impairment (38) 12/18 (67%) 26/28 (93%)

aIn a series of 148 aneurysms with 46 vessel occlusions, intraoperative SEP changes aftervessel occlusion were correlated with postoperative clinical outcome. With SEP changesoccurring independently from time of vessel occlusion, postoperative clinical impair-ment was significantly more frequent than with unchanged SEPs. Modified from [16].

TABLE 15.2 Correlation of Intraoperative SEP Changes with Surgical Eventsin an Earlier Series of 282 Aneurysms from Our Service [16]

SEPEvent N Unchanged Deterioration Loss

Accidental occlusion 22 18 2 2

Intentional occlusion 10 8 1 1

Temp. occlusion 51 29 14 8

Vessel retraction 6 4 2 —

Cerebellar retraction 1 — 1 —

Intent. narrowing 2 2 — —

Others 11 11 — —

Total 103 72 20 11



For monitoring aneurysms of the upper posterior circulation system, visualevoked potentials would, in principle, be suitable. However, it has been shownthat the current intraoperative technique of flash evoked visual potentials doesnot allow for reliable monitoring of the visual cortex or pathways [60–63]. Withaneurysms of the anterior cerebral artery (ACA), tibial nerve SEPs are mostlikely to pick up compromise of the vascular supply of ACA territory, whereasmedian nerve SEPs will not reflect cortical ischemia in this area. Since ACAaneurysms are usually located close to the midline, bilateral tibial nerve stimu-lation is highly recommended, in particular with ACOM lesions. In the lattercase, median nerve SEP monitoring may in theory also be useful, since perfo-rating arteries branching off the ACA (such as Heubner’s recurrent artery) maysupply territories comprising other than lower extremity motor or sensoryfibers. However, median nerve monitoring is rarely performed with ACA orACOM aneurysm clipping at our institution. MEP monitoring has been intro-duced at our institution with all anterior circulation aneurysms to pick upcompromise of perforating vessels, which may lead to motor impairment notreflected by SEPs [12–14]. Contrary to the ACA, the branches of the MCAsupply the sensorimotor hand area on the hemispheric convexity. Therefore,median nerve SEP (and upper extremity MEP) monitoring is performed withMCA aneurysms. Although bilateral recording is desirable, contralateral SEPswill provide most of the relevant information with a limited number of record-ing channels. Clipping of aneurysms of the ICA proximal to its bifurcation willbe sufficiently monitored with median nerve SEPs, which are to be preferredover lower extremity SEPs because of their technical advantages. With aneu-rysms of the ICA bifurcation, tibial nerve SEPs may also be monitored if theACA or its perforators are involved or if sufficient proximal control cannot beobtained. As with MCA aneurysms, unilateral SEP recording is not optimal,but sufficient in most cases of ICA lesions. If perforators are endangered, how-ever, MEP monitoring is a useful addition (e.g., in large PCOM or giant ICAaneurysms). See Figs. 15.3 and 15.4 for examples of intentional and inadver-tent vessel occlusion.

2.2.2.2 Vascular Malformations

Surgery or endovascular embolization of vascular malformations located nearthe central region or close to the sensorimotor pathways can be usefully mon-itored with SEPs [64–66]. Local factors like retractor placement or heat fromelectrocoagulation may damage those structures directly, and SEP recordingmay provide early warning signs. Moreover, vascular malformations may shareblood supply with adjacent brain areas, including sensory regions, and occlu-sion of superficial or deep feeders may compromise perfusion of normal braintissue. SEP recording will allow for test occlusion of those vessels even in the



anesthetized patient. As with aneurysms, the type of SEPs that should berecorded depends on the location and vascularization of the lesion and theinvolvement of perforating vessels. Future monitoring setups will routinelyinclude MEP monitoring in case motor function is endangered.

2.2.2.3 Tumors

When feasible, tumor removal from within or adjacent to the central regionor sensorimotor pathways mainly requires MEP monitoring, since impendingsensory impairment alone will generally not be accepted as a criterion to stoptumor resection. Only with tumors close to or involving the basal ganglia(except the internal capsule), SEPs alone may provide the criterion for how farto proceed with the resection. With insular tumors extending deeply toward the

FIGURE 15.3 Surgeon’s reaction triggered by SEP loss. Median nerve SEPs were monitored duringclipping of a middle cerebral artery (MCA) aneurysm. The aneurysm ruptured during repositioningof a first clip, and the M1 was temporarily closed. A significant reduction of SEP amplitude occurredalmost immediately. Since clipping and suture of the avulsed aneurysm neck were not accomplishedwithin 10 min, the temporary clip was readjusted to close only that M2 branch of the M1 bifurca-tion carrying the aneurysm. SEP recovery provided reassurance to proceed with the closure of theaneurysm base, which lasted a further 20 min. Postoperatively there was a slight transient hemi-paresis. Modified from Fig. 2 in [143].



internal capsule, MEPs will be more useful than SEPs to determine resectionborders (see Section 3). However, the tumor may involve vessels in the Sylvianfissure, or the transsylvian approach may lead to significant vasospasm [67],and SEPs may provide valuable information complementary to MEP monitor-ing in such cases. For complex deep-reaching and vessel-encroaching tumors,the combined use of SEP and MEP monitoring may be considered. If resourcesare limited, however, MEPs should be preferred.

3 INTRAOPERATIVE AND PERIOPERATIVENEUROPHYSIOLOGICAL FUNCTIONAL MAPPING

In supratentorial procedures, functional neurophysiological mapping basicallycomprises median nerve SEP phase reversal techniques for the localization ofthe central sulcus, or direct stimulation techniques used extraoperatively withimplanted grid electrodes and intraoperatively in awake craniotomies. The most

FIGURE 15.4 Inadvertent M2 closure detected by SEP change. Median nerve SEPs were monitoredduring clipping of an MCA aneurysm. Shortly after a seemingly successful placement of the clip, asignificant SEP change occurred. The surgeon was informed, and thorough examination of the situsrevealed an inadvertent closure of one M2 branch. After readjustment of the clip, SEP amplitudesrecovered fully within a few minutes.



common way to use the median nerve SEP phase reversal technique is as a firststep during the resection of a lesion around the motor area. Median nerve phasereversal aids in planning the cortical approach, in determining the precise loca-tion of the motor strip, and in using the ideal stimulation site for motor tractmonitoring during surgery in these areas. Extraoperative mapping via implantedgrid and strip electrodes is mostly used in cases of epilepsy surgery. In additionto giving the same information as a simple phase reversal technique with mediannerve SEPs, it allows additional information to be gained regarding sensory areasand in particular speech areas. Extraoperative mapping via a grid or multiplestrips is therefore useful in all lesions encroaching on one of the two speechareas or encroaching on both the speech and the motor strip. From our experi-ence with over 200 of these patients in our epilepsy surgery series, we areincreasingly applying this technique to a series of regular tumor surgeries whenthe complexity, the location, or other factors seem to warrant such information.

3.1 SEP PHASE REVERSAL

This technique is useful to point out the location of the central sulcus. Theclassic triphasic negative-positive-negative configuration of the early compo-nents of median nerve SEPs with N20 over the sensory cortex changes shapeinto a mirror image with N20 becoming P25 over the motor cortex. This phe-nomenon was initially described by Woolsey et al. [68] and has been used byother authors during epilepsy surgery [69] and tumor surgery [70–72]. Pro-vided that the strip electrode is positioned in an adequate angle across the cen-tral sulcus, the switch in polarity for the early cortical median nerve SEP caneasily be detected. Since both intrinsic and extrinsic brain tumors can easily dis-place cortical structures by 1.5–2.0 cm (which is more than the breadth of agyrus), this can be important information. Figure 15.5 shows a typical case ofa lesion around the central sulcus requiring use of the intraoperative phasereversal method (see also Fig. 15.8).

3.1.2 Technique

Standard stimulation setup and recording parameters for median nerve SEPs areused. The reference electrode is fixed to the skull with its usual reserve elec-trode. The trepanation is planned in such a manner that the lesion can beapproached and that there is enough space to place a two-row strip electrodeacross the presumed central sulcus. In principle, the SEP phase reversal tech-nique can be applied both intra- and extraoperatively. The strip electrode maybe pushed underneath the dura and away from the rim of the trepanation.Having ensured good contact with the brain surface by saline irrigation, oneshould check the electrode impedance to ensure that the electrode has settled


355

FIGURE 15.5 Central sulcus mapping by the SEP phase reversal method. Median nerve SEP phase reversal was recorded in a patient with a left pre-central AVM (Spetzler-Martin grade II). The first precentral electrode (closest to the central sulcus) was selected for intraoperative MEP stimulation andelicitation of MEPs (see Fig. 15.11).



and that artifacts are minimized. If a four to eight channel averager is avail-able, evoked potentials from the two rows of eight contact electrodes can berecorded within 5–10 min, depending on the number of channels and the levelof noise. Since electrodes are located 1 cm apart and the sulci can sometimeseasily be detected or dissected underneath the veins, a delineation of the posi-tion of the central sulcus is usually achievable in well over 90% of cases.Cedzich et al. have summarized some of our experiences [72]. One importantresult was that the presumed localization of the central sulcus as calculated onthe basis of preoperative MRIs was found to be inaccurate as judged by intraop-erative SEP phase reversal in 12% of all cases [72]. Even with modern-day MRItechnology, it may be difficult to precisely and correctly locate the central sulcus,especially if normal anatomy has been distorted by tumor or overshadowed bypathological vascularization. In about 5% of these cases, the redetermination ofthe lesion site was from postcentral to precentral or from central to precentral(Fig. 15.6). Even if a classical phase reversal cannot be obtained, the central sulcuscan often be located by the absence of the classical negative-positive-negative con-figuration of median nerve SEPs across the suspected sulcus (Fig. 15.7).

It is also important that the direction of the two electrode strips pushedacross the sulcus is at least 45° (and optimally 90°) to the assumed direction ofthe sulcus (on-axis vs. off-axis recording [73]). Obviously, the best mediannerve potentials could also be obtained in the area representing the hand, whichmeans the electrode should be neither immediately parasagittal nor just brieflyabove the Sylvian fissure.

Sometimes if orientation is difficult, a four-row strip electrode should beused. The neurophysiology technician then marks the position of the phasereversal potential between the respective electrodes on a schematic drawing forthe surgeon and presents it to the surgeon. The surgeon can then either memorizethe position of the sulcus in this field or can mark it with a sterile cotton strip

FIGURE 15.6 Comparison of preoperative (MRI) data versus intraoperative (SEP phase reversal)localization. In a series of 67 cases from our service [72], the localization of pericentral lesions asdetermined according to preoperative MRI and intraoperative SEP phase reversal was compared. Ina significant number of patients (8 patients, 12%) the lesion was intraoperatively found to belocated differently than was suggested by preoperative imaging, which had obvious consequencesin terms of approach and extent of resection.



placed directly on the cortex. The position with the best P25, which most likelycorresponds to the hand area of the motor cortex, is then used for placement ofthe stimulation electrode for motor tract monitoring. For this purpose, thealready placed strip electrode can be connected to the stimulator and used forstimulating purposes, or it can be replaced by a single 1 cm cup electrode formotor tract stimulation.

3.2 EXTRAOPERATIVE MAPPING WITH GRID

OR MULTIPLE-STRIP ELECTRODES FOR MOTOR,SENSORY, AND SPEECH LOCALIZATION

This technique is applied in lesions in or adjacent to speech areas and motorand sensory cortices. It is mostly used in surgery for chronic and drug-resistantepilepsy, but it is also applied in vascular and tumor-related lesions if the riskis considered high for a standard surgery. The technique of extraoperative

FIGURE 15.7 Alternative localization of the central sulcus by absence of N20 instead of truephase reversal. In this patient with a parietotemporal tumor, median nerve SEPs were recorded viaan (epidural) electrode strip placed across the central region. Although no “classical” phase rever-sal could be obtained, absence of the precentral SEPs allowed for identification of the central sulcus,which correlated well with anatomy.



mapping implies two different procedures: the implantation of the grid fol-lowed by the neurophysiological evaluation, and as a second step the resectionof the lesion. The alternative method to this two-step procedure is a one-stepprocedure whereby the electrophysiological functional mapping is done intra-operatively with the patient being awake during craniotomy. This intraopera-tive mapping technique was pioneered by Foerster, was used extensively byPenfield, and was later used extensively by Goldring, Ojeman, and the Montrealgroup. It has recently been revived for glioma surgery in several centers [71,74–77]. Both methods have strengths and weaknesses. The main weakness ofthe two-step method is that two surgical procedures with anesthesia are needed.For review of advantages, see [78]. The advantage of this method is that testingcan be done in a patient who is not under stress and who is not sedated. Mostimportantly, testing can be expanded as long as needed. In our settings, usuallytwo sessions of approximately 3 hr are needed to get a reliable map of thespeech area, the motor cortex, the sensory cortex, and the areas with interictalspikes for the epilepsy surgery cases. Proponents of the awake craniotomy pro-cedure maintain that the patients do not find it stressful and are cooperative,and that generalized seizures are rare. We prefer extraoperative mapping mostlybecause of its more reliable nature and the chance to reproduce results on asecond day of testing. It also has the advantage that in patients with epilepsy,lengthy EEG recordings to detect zones of interictal spiking, as well as ictalvideo-EEG recordings, are easy to perform. For several reasons, extraoperativefunctional mapping is obviously superior to acute intraoperative stimulationmapping in terms of reliability and precision of results (see [78] for review). Onthe other hand, it entails the risks of an additional operation, and it lengthensthe inpatient hospitalization considerably if the electrode implantation is per-formed for reasons of functional mapping alone.

3.2.1 Technique

When planning the trepanations, it is important to keep in mind that they mustbe large enough to accommodate the grid electrodes, which are usually 8 by 8cm in size, or several strip electrodes, which come in sizes of 2 by 8, 2 by 4, or4 by 8 cm. For this application, the larger rectangular subdural grid electrodeswith up to 8 by 8 contacts are particularly well suited (see [79] for review). Inthe last 2 years it has been our routine to do a digital photograph of the exposedbrain surface with and without the electrode in situ. This has the advantage thatduring a second stage the electrode grid can be removed, and the orientationwill be easily maintained using the two photographs without having an elec-trode in the surgeon’s way or having to cut the electrode in order to delineate



the area to be preserved or resected. Craniotomies are placed in such a fash-ion that both the lesion and the functional areas of interest can easily bereached. The electrodes should usually be placed so that all the areas are opento direct visual observation. This implies that craniotomies are larger than forthe standard removal of a tumor or a lesion in another brain area. Electrodecables are led outside through separate small incisions in the dura, led aroundthe bony borders, which have been smoothed by rongeur, and then led throughthe scalp again via a separate small incision. Both the dural exit and the scalpexit are closed with an encircling pouch suture. Watertight sutures cannotalways be achieved, but they are possible with a very careful suturing techniquein most cases. The patient is referred to the electrophysiological unit the dayafter surgery, and a first recording session is done, usually lasting at least 2.5–3 hr.Since all the procedures have been explained to the patient in advance, coop-eration is usually very high. Extraoperative mapping can include the standardmedian nerve SEP phase reversal, but also recording for interictal spikes and,of course, mapping of areas where stimulation induces dysnomia or speecharrest, or motor and sensory phenomena.

In the presurgical evaluation of epilepsy, chronically implanted subdural ordepth electrodes are widely applied for invasive seizure recording and hence forthe determination of the epileptogenic area. Circumscribed electrical stimula-tion may induce clinical or subclinical seizures, especially in the zone of onsetof spontaneous seizures. However, the localizing value of those inducedseizures has been controversial [80, 81].

In epilepsy surgery programs worldwide, stimulation mapping via chroni-cally implanted grid electrodes is applied whenever an overlap of the epilepto-genic area with eloquent cortices is suspected. Three types of eloquent corticesare of major interest:

1. The primary motor cortex2. The primary sensory cortices, especially the visual cortex and the

somatosensory cortex3. Association cortices with more or less circumscribed representations of

higher cognitive functions, particularly the language cortices and theleft perisylvian association cortex

In the primary motor cortex, single stimuli typically elicit single clonic uni-lateral movements according to the topography of the motor homunculus inthe precentral gyrus. High-frequency (50 to 60 Hz) stimulus series are res-ponded to by slower, rather tonic contralateral movements. In the primarysensory cortices, high-frequency trains of stimuli also elicit positive responsesaccording to the respective modality, namely, visual or auditory pseudohalluci-nations and somatosensory phenomena. On the other hand, in higher association



cortices, mainly negative phenomena (i.e., specific loss of some aspect of cog-nitive behavior) are observed. Because of the different organization of thosefunctional networks, the represented functions are acutely impaired duringstimulation.

FIGURE 15.8 Lesions at the deeper part of the precentral sulcus, undermining the precentralgyrus. Schematic presentation of a grid with small electrodes of 0.5 cm distance center to center.The position of the central sulcus is most easily determined by initial phase reversal of median nerveSEPs for the hand area, and it can be confirmed by combined use of stimulation mapping and directvisualization following the direction or path of the identified sulcus.



3.2.1.1 Mapping Using the Stimulation Technique

In the University of Bonn epilepsy surgery program, electrical stimulation isperformed and documented in a video-electrocorticography setting. Stimula-tion is performed with a Grass S88 stimulator and Grass constant-current unit(Grass Instruments, Astro Med, West Warwick, RI) by way of a step-by-stepstimulation of neighboring electrodes in a bipolar montage. On the second day,the whole procedure, which may last up to 3 or 4 hr, is repeated with a mon-tage orthogonal to the preceding one in order to improve spatial resolution andto confirm the previous results. If the data are contradictory or inconclusive, theprocedures will be repeated. Stimulus intensity ranges from 1 to 15 mA,depending on the threshold of after-discharges. For intraoperatve stimulationparameters, see Table 15.4. The stimulation rate ranges between 10 and 60 Hz,with a train duration of 3–8 s, depending on the task (see following text). Motorand sensory cortices are mapped with a short stimulus train. For mapping oflanguage and associated perisylvian functions (reading, calculation, writing,etc.), a train of stimuli below the threshold producing after-discharges is deliv-ered for the duration of patient instruction and performance. After priorinstruction, specially selected short tasks are given repetitively with and with-out stimulation. For language testing, the following subfunctions are evaluated:naming, continuous speech, repetition, body commands, reading, and sentencecomprehension. Additionally, simple tasks from the Token Test [82] are per-formed under stimulation. Repeated testing yields a sufficiently reliable map ofeloquent areas. In epileptic patients, this documentation is supplemented by anoverlayed map of ictal onset sites, and additional electrophysiological data arerecorded with the very same electrode array.

It needs to be mentioned that the functional inhibitory effects of electricalstimulation, such as dysnomia or speech arrest, do not always and preciselyindicate that the brain directly underlying that particular electrode representsthe speech center. Spreading effects to adjacent cortical areas (e.g., by short-reaching U-fibers) are possible. In Fig. 15.9, for example, the stimulationeffects with sensory speech phenomena are much bigger than Wernicke’s areaas known from functional MRI testing. Another argument underlining thiscautionary remark is the wide-spread disinhibition of effects on speechdescribed by Ojemann, which reach anteriorly on the temporal lobe. If thesestimulation effects would represent the true speech cortex, standard temporallobectomy should produce speech deficits in a considerable proportion of cases.This is not the case, however, as shown by Hermann and Wyler in a prospec-tive comparative study on temporal lobe resection with and without languagemapping [83, 84].

As for rivaling methods, the localization of primary sensory and motor areascan be determined noninvasively by means of functional MRI with increasingvalidity [85]. The primary motor area can be identified indirectly using the



intraoperative SEP phase reversal technique [72]. Results from intracarotidamobarbital testing correspond well with electrical language mapping [86], butthe Wada test is insufficient for determining the intrahemispheric topographyof language areas. For the depiction of language areas, functional MRI hasrecently been shown to be an increasingly valuable method as well [87]. How-ever, neurophysiological mapping must still be considered an indispensableprocedure in presurgical evaluation, particularly in epilepsy surgery programs.

3.3 INTRAOPERATIVE ELECTRICAL STIMULATION

OF MOTOR CORTEX AND WHITE MATTER

An alternative method for functional mapping of the central region in anes-thetized patients is to directly stimulate motor structures. SEP phase reversalessentially identifies the motor cortex as it relates to the somatosensory handor foot area. With increasing distance from these areas, and with distortion of

FIGURE 15.9 A patient with parietal cortical dysplasia. Motor, sensory, and speech phenomenacan be identified. Stimulation in the region of the angular gyrus elicits motor and sensory speech phe-nomena. The dispersion of speech phenomena is marked and may be induced by cortical dysplasia.Occasional motor phenomena may be recorded following stimulation of the postcentral gyrus. Thiscase demonstrates that conventional knowledge about cortical function may be misleading.



the local geometry, mapping results may become unreliable. In this connection,SEP phase reversal may not be obtained, and identification of the motor cortexmay only be possible with regard to anatomical criteria. Despite clear advan-tages of the phase reversal method, direct motor mapping is desirable in suchcases. In fact, it has been repeatedly shown that a combination of direct motormapping and SEP phase reversal allows for reliable identification of the motorarea with a success rate close to 100% [72, 88, 89]. Two major methods fordirect mapping of the motor cortex via electrical stimulation are currentlyapplied. The first and more common method uses bipolar stimulation (i.e., thePenfield technique), with observation of movement during craniotomy in anawake patient. Or, if the patient is anesthetized, EMG can be used. This methodhas been used for many years [60, 71, 74, 75, 77, 88, 90–95]. However, it hasbeen found to have conceptual and practical weaknesses and disadvantagesthat limit its use. The second method, using monopolar stimulation withrecording of MEPs, has been developed over the last 10 years [72, 89, 91, 96].Although it is not yet as commonly used as the traditional technique, it seemsto lack some of the drawbacks and provides the additional possibility of con-tinued MEP monitoring throughout the operation. Both methods are describedonly broadly here. A detailed overview of more recent techniques is given inSections 2 and 4.

3.3.1 Bipolar Cortex Stimulation (Penfield’s Technique)

Penfield [97] established the method of eliciting movement using a bipolar elec-trode to stimulate the exposed motor cortex with 50 to 60 Hz frequency stim-ulation. This method has been developed further by different groups over thelast 50 years [68, 71, 74, 75, 77, 88, 90–95]. Whereas the original method relieson observation of tonic movements after cortical stimulation, recording of elec-tromyographic (EMG) responses has been introduced as an improvement insensitivity and safety [93].

3.3.1.1 Stimulation

The stimulation technique is based on the activation of cortical circuitry byrepetitive application of electrical pulses. The current paradigm [71, 91] usesbipolar, biphasic rectangular pulses of 1 ms duration and 2 to 20 mA intensity,delivered for 1–4 s at a rate of 50–60 Hz via electrode strips or a hand-held stim-ulator with spheric steel tips spaced at about 5 mm apart. Stimulus intensity isincreased in 1 to 2 mA steps, starting from a low level of 3–5 mA, until a motorresponse is recorded. The stimulus train is delivered for 1–4 s, until a responseis obtained (if present) with a given stimulus intensity. Sites of successful stim-ulation can be marked with sterile tokens.



3.3.1.2 Recording

Motor responses can be observed as limb or face movements. The limbs needto be sufficiently exposed so that the entire side contralateral to the craniotomycan be observed. With sufficient stimulation, brief but tonic movements areelicited that allow for a determination of the stimulated cortex’s specific motorfunction. The movement usually is small so that positioning of the patient andsurrounding equipment will not be disturbed. As an alternative to the observa-tion of movements, EMG recording with this stimulation paradigm has beenrecently described [89, 93]. Subdermal needle electrodes are placed into repre-sentative face, trunk, and limb muscle groups. The recording scheme dependson the location of the lesion. If precise mapping is the main goal, as many dif-ferent muscles as possible should be recorded from. If subtle cortical mappingis less important than a greater extent of the activation given the limited numberof amplifier channels, the two electrodes of each channel may be placed to con-nect related muscles groups, e.g., elbow flexors and extensors [93]. Neither move-ment observation nor EMG recording can provide quantitative information.

3.3.2 Clinical Application

3.3.2.1 Cortical Mapping

The most common application of this mapping method is identification anddelineation of the motor cortex with lesions within or adjacent to the centralregion. In a recent series of 66 such operations [93], motor responses could beregistered by either EMG recordings or observation of movement in 79% ofcases. In another recent study [89], motor responses were obtained in 95% ofmotor cortex stimulations, but were also present in almost 30% of premotor andin only 9% of postcentral stimulations. Whereas the sensitivity of the methodappears somewhat low in the former series, the latter result indicates a doubt-ful specificity of the method with regard to motor cortex identification.

3.3.2.2 Subcortical Stimulation

There are anecdotal reports on the use of this method for stimulation of sub-cortical motor tracts [92–94]. These concern its use for both defining resectionborders with tumors approaching deep motor (and other functional) pathways,and for determining the extent of functioning tissue within the boundaries ofinfiltrative gliomas. However, the latter applications were not easy to replicateat our institution. Obtaining a muscle response by 50 to 60 Hz electrical stim-ulation of the motor cortex is based on the activation of motor cortex circuitry,which is a very powerful mechanism for reaching the α-motoneuron firingthreshold. Producing the same effect by subcortical (axonal) stimulation requiresmuch higher stimulation frequencies than 50 or 60 Hz (see following text).



Nevertheless, a reliable technique for stimulation of subcortical motor struc-tures would obviously be a very attractive intraoperative aid to avoid lesioningthe motor tracts.

3.3.2.3 Advantages and Disadvantages

The method is virtually the oldest intraoperative electrophysiological methodapplied for routine use, and much experience has been gathered. A number ofhigh-quality publications enable a reliable assessment of the adequacy in a givensituation. However, the limited specificity of the method, its lack of quantifiableresults and continuous monitorability, as well as safety issues (see Section 5),trigger the search for an alternative, and less problematic, technique.

3.4 MEP MAPPING

The major part of the stimulation and recording paradigm for mapping pur-poses is equivalent to the monitoring technique presented in Section 4.1. There-fore, only the basic concepts, as far as they are important for an understandingof the mapping method, will be presented here.

MEPs recorded from limb muscles are elicited by short trains of electricalpulses delivered to the exposed motor cortex. Because of the somatotopic orga-nization of the motor cortex, motor responses recorded as evoked potentials frommuscle groups provide a functional map of the stimulated cortical area. Contin-uous monitoring of motor tract functional integrity would, in principle, be pos-sible with recording of spinal volleys alone, which are not significantly affectedby anesthesia. Conversely, motor mapping requires specific identification of cor-tical regions beyond mere identification of the motor strip. This cannot beachieved by a recording of spinal activity, since a differentiated mapping of thespinal motor somatotopy is not yet possible. Therefore, recording directly fromrelevant muscle groups must be included in the mapping paradigm.

3.4.1 Technique

3.4.1.1 Stimulation

Typically, trains of five (four to nine) monopolar anodal, rectangular elec-trical pulses of 300 (200–500) µs duration, with an interstimulus interval of2–4 ms, are delivered to the exposed cortex via a hand-held stimulator or, morecommonly, via an electrode grid covering the area of interest. The referenceelectrode is placed at Fpz or some other suitable remote cephalic site.

For mapping purposes, as low as possible suprathreshold stimulus intensi-ties are desirable to preserve the specificity of the method, since strong stimu-lation may lead to activation of neurons not located directly beneath the



stimulation site. Threshold intensity is usually below 15–20 mA. When muscleMEPs are being recorded, extrapyramidal motor fibers may theoretically be acti-vated as well, but the actual mono- or oligosynaptic corticospinal connectionsdescending from the primary motor cortex are obviously more sensitive to elec-trical stimulation.

3.4.1.2 Recording

Although phasic muscle twitching is often elicited, observation of move-ments is not practical. MEPs, or compound muscle action potentials (CMAPs),are recorded by differential surface electrodes or, more commonly, by sterilesubdermal needle electrodes. Impedances should be below 10 kΩ. Electrodesare placed in a belly-tendon fashion if single muscles or muscle groups are tobe mapped. If a comprehensive sampling of all relevant muscle groups isrequired with a limited number of recording channels available, electrodes fromtwo adjacent muscle groups can be connected to one channel. The recordedsignal can be quantitatively evaluated in terms of latency, amplitude, width, andshape. Whereas this is important with continuous MEP monitoring, it is lessrelevant with mapping, although differences in amplitude between differentstimulation sites may contribute to the specificity of the method.

3.4.2 Clinical Application

3.4.2.1 Cortical Mapping

The main goal of using this technique is identification and delineation of themotor cortex, as well as determination of the lesion’s position with respect to it.For superficial lesions within or directly adjacent to the motor cortex, resectionborders may be determined with the aid of the mapping procedure. With deeplylocated lesions, the transcortical approach can be planned with greater safety.This kind of motor mapping is usually performed in combination with record-ing of SEP phase reversal. Recent reports [72, 89, 91] showed a sensitivity andspecificity of over 90% of combined MEP and phase reversal recording (as wellMEP recordings alone) with regard to motor cortex identification [91]. MEPswere elicited in 97% of primary motor cortex stimulation, but in only 14.6% ofpremotor and in 8% of postcentral stimulation. The latter results are better whencompared with the traditional stimulation method [91] (see Section 3.3).

3.4.2.2 Advantages and Disadvantages

In principle, both methods presented here are suitable for mapping the motorcortex. The major advantages and disadvantages of the traditional method arediscussed in Section 3.2.1.1. The more recent method of MEP mapping is notsupported by clinical experience. Nevertheless, it appears superior in terms of



sensitivity, specificity, and reliability [91]. At the same time, it is safer [96] andallows for quantitative evaluation and continuous intraoperative monitoring.Table 15.4 summarizes stimulation and recording parameters for both methods.

4 MEP MONITORING

The preservation of motor function is a major concern with surgery in manysupratentorial lesions. At the same time, the most radical resection possible isdesirable with regard to postoperative quality of life [98–100]. It is thereforedesirable to obtain a clear delineation of motor cortex and a continuous moni-toring of the motor tracts’ functional integrity. Although preoperative func-tional imaging may help to identify the structures [101], those methods stilllack the required precision at this point of time. Furthermore, they cannot beused for continuous intraoperative functional assessment. In fact, no imagingor mapping technique is conceivable that may replace preoperative directrecording of the actual neural activity.

The intraoperative monitoring of MEPs with supratentorial procedures hasonly developed over the last decade, and its status has not yet reached that of astandard method such as SEP monitoring. In fact, this application must still beconsidered developmental. Beyond preliminary reports, no large series has yetbeen published [20, 72, 96, 102] on the clinical use of MEPs with supratento-rial surgery. The situation is different with spinal cord MEP monitoring, wherean increasing number of clinical reports converge on some general principlesregarding recording technique and clinical interpretation [22, 103–107]. Basedon these principles, this method is routinely applied in many institutions thatperform spinal, medullary, or aortic surgery. Our method of MEP recordingwith certain supratentorial procedures, as well as some considerations andexperiences with regard to its clinical application, is now described.

TABLE 15.4 Stimulation and Recording Parameters for IntraoperativeMapping of the Motor Cortex

Bipolar stimulation MEP mapping

Polarity Bipolar Monopolar anodal

Phase Biphasic/monophasic Monophasic

Frequency 50–60 Hz 200–500 Hz

Amplitude 2–20 mA 5–25 mA

Pulse width 1 ms 50–500 µs

Number of pulses Sustained stim 1–4 s 4–9 pulses

Motor response Movement, EMG CMAP

Filtering 10 Hz–3 (10) kHz 10 Hz–3 (10) kHz

Averages None None/few



4.1 TECHNIQUE

4.1.1 Development of Technique

Experimental work performed over the last 50 years [108, 109] has led to arather detailed, though still very incomplete, understanding of the physiologi-cal processes occurring after electrical stimulation of the cerebral cortex (seeChapter 1 of this book). Since the introduction of transcranial electro- and mag-netic motor cortex stimulation [110, 111] with recording of spinal and muscleevoked activity (MEPs), various attempts were made to use this technique forintraoperative motor monitoring purposes, mainly in spinal surgery [103,112–117]. However, general anesthesia seemed to prevent reliable intraopera-tive recording of myogenic MEPs. In 1993, Taniguchi et al. from Bonn [96] pro-posed a modification of the stimulus paradigm that turned out to be suitable forboth direct cortical [72, 91, 96] and transcranial [118, 119] stimulation undergeneral anesthesia. The method exploits the fact that the inhibitory effect ofmost anesthetics at the α-motoneuron can be overcome by temporal summa-tion [120] of excitatory postsynaptic potentials elicited by a train of descend-ing volleys. This is directly elicited via corticospinal tract (CT) axons activatedby transcranial stimulation. Only with this facilitation does reliable intraoper-ative recording of muscle motor activity become possible. Other methods offacilitation had previously been tried (e.g., H reflex).

4.1.2 Stimulation

The current flow necessary to activate the motor tract can be induced by elec-tric [108, 111] or magnetic [110] pulses, the latter also being applied transcra-nially. Both direct cortical and transcranial stimulation are suitable withmonitoring for supratentorial lesions. If the motor cortex is exposed, direct cor-tical stimulation is preferable. With electric pulses delivered directly to theexposed cortex, descending pyramidal axons are activated at one of the firstinternodes [108], while the site of activation appears to be deeper in the whitematter with transcranial stimulation [121]. Cortical circuitry may also be acti-vated with direct electrical stimulation, leading to a variable series of corti-cospinal volleys (I waves) following the first volley from direct axonalexcitation (D wave) [108]. Conversely, transcranial magnetic stimulation, withthe coil axis oriented tangentially to the cortex, seems to activate only (or pre-dominantly) cortical circuitry [122]. Therefore, the inhibition in the cerebralcortex induced by anesthesia is easily seen if MEPs are exerted with magnetic,rather than with electrical, stimulation. In practice, MEPs elicited by magneticstimulation start to deteriorate during induction of anesthesia. Since it does notprovide other advantages but does have a number of disadvantages (e.g., depres-sion by anesthetics, strong magnetic field, bulky equipment, slow repetition rate



of magnetic stimulators, overheating of the coil, etc.), we will focus here onelectrical stimulation. Most parameters applied with transcranial stimulationcorrespond to those employed with direct cortical excitation. Since transcra-nially elicited MEPs are usually more difficult to obtain, and since the record-ings tend to be less stable in general, it is important to determine the optimumparameters, which can vary between patients.

4.1.2.1 Polarity

Monopolar anodal stimulation has turned out to be the most efficient for cor-tical stimulation [108, 121]. With an anodal stimulus applied to the cortex, cur-rent is assumed to enter at the apical dendrites, leading to depolarization at theproximal Ranvier internodes of the CT axons [108]. Conversely, current fromcathodal stimulation is thought to lead to hyperpolarization, which preventsexcitation. In practice, cathodal cortical stimulation at a somewhat higherintensity level also leads to reliable motor activation in most cases.

4.1.2.2 Stimulation Site

Direct cortical stimulation is applied with lesions that require exposure ofthe motor cortex, or if craniotomy enables the subdural advance of surface elec-trodes over the central region. In order to perform successful stimulation, themotor cortex has to be identified, which is often not possible by mere anatomiccriteria, given the limited view. Therefore, some kind of functional mappingmust precede the actual MEP recording. It is also possible to perform preoper-ative functional MRI and feed the data into a navigation system. The functionalMRI data may then be transposed onto the cortex during surgery. This, how-ever, is an expensive way to replace the quick phase reversal technique.

In principle, the mapping procedures described in Section 3.3 could be usedto search systematically for the optimum stimulation site. The point of bestresponse (highest amplitude MEPs or lowest threshold for eliciting them)would be chosen. In practice, however, this procedure would be relatively time-consuming and might even give unreliable results. For these reasons, SEP phasereversal is always performed preceding cortical stimulation (see Section 3.1).The point of the best precentral response (i.e., highest amplitude of P25/N40) isconsidered closest to the motor hand/foot area (N40) and is selected for motorcortex stimulation, while the second electrode (cathode) is placed at Fpz.

In most cases, the craniotomy allows for median nerve SEP recording. Theelectrode is placed as close as possible to the sensorimotor hand area. Withlesions located predominantly at the paramedian central region, tibial nerveSEP phase reversal recorded from the paramedian motor cortex is advanta-geous. If the recording electrode cannot be placed optimally, full phase reversal



may not be obtained. In particular, if the electrode strip is positioned off axis(i.e., does not equally cover sensory and motor hand area) and crosses the cen-tral sulcus, only an absence of potentials from the precentral gyrus, afterattempts to record with the strip electrode, would indicate that motor cortexhas been identified (Fig. 15.7) (for details see [69]). With reference to the localanatomy, it is usually still possible to reliably identify the central sulcus and themotor cortex [72, 89]. Similar problems may arise with extra-axial tumors likemeningiomas or unusual constellations of vasculature preventing subduraladvancement and correct positioning of the electrode strip. Alternatively, MEPscan still be successfully recorded by looking for the best MEP amplitude usingan electrode strip and trying various electrodes. However, if the local geometryis significantly distorted (e.g., with a truly central lesion), unambiguous iden-tification of the motor strip may not be possible with mere SEP phase reversal.

The optimum site for transcranial stimulation has not yet been determined.Several different stimulation electrode montages have been described: The stim-ulating anode can be placed at Cz+2cm to Fpz or Fz (Cz+2cm indicating ananterior shift of about 2 cm from the standard Cz position of the International10–20 System in order to obtain placement over the motor cortex). Use of a cir-cumferential cathode from linked electrodes at Fz, F3/4, and A1/2 has provedto be more efficient [124]. Other electrode montages include positions C3+2cm/C4+2cm and C1+2cm/C2+2cm (as before, 2 cm anterior to the standard posi-tions of the International 10–20 System), corresponding to the motor hand areaand positions somewhat more medial [118, 123, 125]. Stimulation of C3+2 cmversus C4+2cm, with the cathode placed over the contralateral hemisphere withupper-extremity MEP recording and over the ipsilateral hemisphere with lower-extremity MEPs, has been shown to be most efficient but produces pronouncedtwitches from contractions of the back musculature. The twitches are consid-erably lower with stimulation sites C1+2cm/C2+2cm or if the cathode isplaced at Cz+2cm, but the stimulus efficiency is usually lower as well. Nev-ertheless, particularly with recording of MEPs from the lower extremities,which requires high-intensity stimulation, positions C1+2cm/C2+2cm may pro-vide the best trade-off between high efficiency and low twitching. If the patientis in a sitting position, subdural air may collect intracranially, preventing tran-scranial stimulation with the standard electrode montage. In those cases, stim-ulation electrodes may be placed laterally/caudally from C3+2cm/C4+2cmpositions [59].

4.1.2.3 Intensity

The threshold intensity at which a motor response can be recorded obviouslydepends on various factors, such as electrode position, anesthetic regimen, andapplication and degree of relaxation. With direct cortical stimulation, 10–15 mA



corresponding to 40–60 V at typical impedances around 2.5–6.0 kΩ is usuallysufficient. With optimal electrode placement, 5 mA can be sufficient. Even withsuboptimal electrode placement, preexisting paresis, partial muscle relaxation,or other interfering factors, 25–30 mA is very rarely to be exceeded. With tran-scranial stimulation, about 10–20% of the applied current reaches the motorcortex [126]. For eliciting upper extremity MEPs, 50–100 mA is usually suffi-cient, while for lower extremity MEPs, a considerably stronger transcranialstimulation intensity of up to 150 mA or even higher is often required. Thecommon commercially available stimulating devices do not provide such high-intensity output at sufficiently long duration of stimuli and high-stimulationrepetition rate. In practice, stimulus intensity appears to be more importantthan stimulus duration, and pulses lasting 50–100 µs are acceptable, althougha significant superiority of stimuli lasting 500 µs has been shown [127]. Withconstant voltage stimulation, up to 1000 V output can be obtained from cur-rent monitoring hardware using a stimulus duration of 50 µs.

For mapping of the exposed cortex, stimulation at threshold may be ade-quate. For continuous monitoring purposes, an intensity somewhat abovethreshold is usually selected to obtain stable MEP monitoring. Since it couldlead to a misinterpretation of MEP behavior, stimulation intensities higher thanthat are not recommended, both in order to not deliver unnecessary chargeload to the brain, and to avoid excitation of the descending CT fibers caudal tothe lesion. For eliciting MEPs from remote sites of the cortex after direct corti-cal stimulation (e.g., simultaneously from face and the lower extremities),stronger stimulation may be necessary to obtain reliable responses. However,the lesion is always deeply located in such situations.

4.1.2.4 Pulse Duration

In our experience, pulse width is not a very important factor with direct cor-tical stimulation. With this technique, pulses lasting 200–300 µs are alwayssufficient, and the use of longer pulse width may mean unnecessary load to thebrain. With transcranial stimulation, pulse width seems to play a more signifi-cant role.

4.1.2.5 Number of Pulses in Train

Since a higher number of pulses will lead to summation of more EPSPs at theα-motoneuron, it will in principle lead to better motor responses. Dependingon the frequency at which the pulses are delivered (interstimulus intervalwithin the train), there is a limit with regard to how many successive excitatorypostsynaptic potentials (EPSPs) can actually overlap and summate for a moreefficient depolarization. However, it has been shown that sustained synaptic



depolarization at the motoneuron leads to repetitive firing of the neuron [128],so that a longer train of stimuli may eventually lead to a better motor response,without increased depolarization. With direct cortical stimulation, more thanfour to six pulses will rarely be necessary.

4.1.2.6 Interstimulus Interval (ISI) Within Train

The findings on ISI are somewhat controversial [96, 118, 123, 125]. Whilein a number of clinical studies the highest MEP amplitudes were obtained at atrain frequency of 350–500 Hz (ISI of 2.0–2.8 ms) [96, 118, 125], it has beenargued from experimental findings that a frequency of about 250–350 Hz maybe most efficient [123]. According to our clinical experience, all train stimula-tion frequencies between 250 and 500 Hz are about equally efficient with cor-tically elicited MEPs, while transcranial stimulation may be more successfulwith longer ISIs (lower train stimulation frequencies).

4.1.2.7 Train Stimulation Rate

Another fundamental question is at which rate to repeat stimulation. Obvi-ously, frequently recording MEPs will increase the sensitivity of the methodfor detecting impending motor damage. In our experience a repetition every15–30 s is sufficient with many supratentorial procedures because of the slowpace at which such an operation usually proceeds. In certain situations (e.g.,when approaching motor tracts during resection or after application of a clipto a blood vessel), the stimulation rate may be increased up to 1 Hz or evenfaster for a short period. During monitoring of MEPs in supratentorial lesions,preserving them is very important to predict a good motor outcome. Con-versely, convincing data exist with spinal cord monitoring that show that themere preservation or loss of muscle MEPs correlates with clinical outcome,whereas changes in amplitude and latency do not influence prognosis [22].Figure 15.10 shows the influence of varying stimulation parameters on MEPlatency and amplitude.

4.1.3 Recording

Responses after transcranial or direct cortical stimulation can be recorded fromthe spinal cord as well as from peripheral nerves and muscles as spinal, neuro-genic, and muscle MEPs. Eliciting movement after motor cortex stimulationunder conditions of general anesthesia is not possible in a significant numberof patients, and it does not provide quantifiable information [89, 93]. Record-ing of axonal, synaptic, or neuromuscular electric activity (MEPs) has greatlyreplaced the observation of movements with most stimulation paradigms.



4.1.3.1 MEPs Recorded from the Spinal Cord (D and I Waves)and Neurogenic MEPs (recorded from Peripheral Nerves)

Theoretically, motor evoked activity over the spinal cord could be recordedfor monitoring supratentorial motor pathways. During spinal and intramedullarysurgeries, recording of epidural MEPs has become a standard monitoring pro-cedure in a number of institutions [123, 129], and semiquantitative correlationsbetween intraoperative MEP findings and motor outcome have been establishedfor those applications [22]. In practice, however, invasive recordings for D wavesfrom the spinal cord are rarely used for monitoring the supratentorial portion

FIGURE 15.10 Influence of varying stimulation parameters on MEPs recorded from the thenarmuscle and elicited by transcranial stimulation (C3+2cm vs. C4+2cm). The following parameterconstellation was varied systematically: five anodal pulses of 300 ms duration and 100 mA inten-sity were applied with an interstimulus interval of 2 ms (500 Hz) using constant current.



of the CT [102, 130]. Transcranial or exposed motor cortex stimulation elicitsa series of volleys descending through the CT (D and I waves; see Chapter 2 inthis book). If converging corticomotoneuronal output leads to a sufficient depo-larization of the α-motoneurons, further volleys descend via the peripheral nervetoward the neuromuscular endplate. Axonal activity can be recorded as D and Iwaves via epidurally placed catheter electrodes [123]. The signal-to-noise ratiois usually good enough to allow for unaveraged recording. Occasionally, a fewaverages, rarely more than 3–10, are required. The main advantage of this record-ing technique is the relative refractoriness of D waves to the effects of generalanesthetics, contrary to I waves, which are more easily suppressed by manyanesthetics. With surgeries that do not provide access to the epidural spinalspace, in particular with supratentorial lesions, the recording electrodes mustbe inserted via Touhy needles, which adds minimal but still additional risk.Although this may be the main drawback of the method, there are further dis-advantages of spinal MEP recording with respect to supratentorial monitoring.Epidural recording does not reflect the somatotopy of the motor cortex; thus itallows for neither functional mapping nor selective monitoring for upper andlower extremities, as is possible with MEP recording from muscles. Corticonu-clear tract volleys cannot be recorded at all, so facial paresis of central origin willremain undetected. Nevertheless, identification and global monitoring of largeparts of the motor cortex are possible by spinal MEP recording [102, 130]. Asuccess rate of only 80% for spinal MEP recording after direct cortical stimula-tion has been described [102]. In this series, the recording electrodes wereinserted the day before surgery. For patients in whom reliable monitoring wasachieved, a good correlation between spinal MEP behavior and postoperativeoutcome was found.

Recording neurogenic MEPs (from the peripheral nerves) has been advo-cated with spinal procedures [131, 132], mainly after direct spinal rather thancortical stimulation. Application of this technique has not been described as yetfor supratentorial procedures. The major potential advantage as compared withmyogenic MEPs is the insensitivity toward muscle relaxants. Theoretically, amore differentiated monitoring may be possible with recording activity fromperipheral nerves rather than spinal cord activity. However, only a few majornerves supplying upper and lower extremities are suitable for this rather trickymethod, which requires the averaging of about 100 additional responses due tothe low signal-to-noise ratio. Lateralized recording is possible, however. Otherthan spinal responses, neurogenic MEPs have the same sensitivity toward anes-thesia as muscle potentials. Therefore, successful recording requires the samemodified stimulation paradigm as described in Section 4.1. In summation, neu-rogenic MEPs do not seem to provide significant advantages over spinal MEPsin monitoring for supratentorial surgeries. (Note: A critical review of thismethod can be found in Chapter 2).



4.1.3.2 Muscle MEPs

Recording MEPs from the muscle as the actual end organ of the motorsystem makes possible a valid assessment of the system’s overall functionalstate. Unlike spinal recordings, placement of recording electrodes in the muscleis minimally invasive. With the current anesthetic regimen and the adequatestimulation paradigm, reliable recording of muscle responses has become fea-sible. Recorded potentials represent CMAPs, or more specifically, muscle motorevoked potentials (mMEPs).

4.1.3.3 Electrode Montage for Recording mMEPs

Muscle MEPs are most readily recorded from distal limb muscles, the corti-comotoneuronal supply of which includes the highest proportion of mono- oroligosynaptic connections. Thus a typical electrode montage includes distalmuscles of upper and lower extremities (e.g., forearm flexor, thenar, or hypo-thenar muscles and tibialis anterior and possibly extensor digitorum muscles).Other muscle groups typically monitored are the orbicularis oculi and orbicu-laris oris, the trapezoid, the biceps and triceps brachii, the quadriceps femoris,and the soleus muscles. Which muscle groups are selected for monitoring in agiven patient depends on various factors, including the location of the lesion,the necessity of detailed intraoperative motor mapping, and technical con-straints (number of available recording channels, etc.). With increased sensi-tivity (more muscles monitored) and unchanged specificity, the rate of false-positive responses will increase. According to the experience with MEP moni-toring at our institution, a montage including the orbicularis oris, thenar or fore-arm flexor, and tibialis anterior muscle will pick up basically all motor impairmentthat can be found on postoperative examination. Depending on the exact loca-tion of the target lesion, additional muscles may be included in the recordingscheme. Regardless of the location of the lesion, merely recording from onelimb may miss impending damage elsewhere.

4.1.3.4 Filtering

Muscle MEPs may contain a large degree of high-frequency activity. There-fore, filtering must be performed with great care, avoiding too tight bounds. A10 Hz to 3–10 kHz band-pass is usually suitable. The signal-to-noise ratio isusually quite excellent in terms of high-frequency noise, since MEP amplitudeis often in the mV range. Conversely, a strong low-frequency electric stimulusartifact may occur that cannot usually be filtered out without affecting thesignal. Thorough grounding of the patient is important with regard to bothsafety and recording quality.



4.1.3.5 Sweep Length and Averaging

Sweeps of 70 ms will be sufficient to record motor responses from both upperand lower extremity muscles. With preexisting paresis, MEP latency may increasesignificantly, and sweep length may have to be adapted. Because of the highamplitude of a normal mMEP response, averaging is not necessary in most cases.With partial neuromuscular block, inappropriate anesthesia, or preexisting pare-sis, MEP amplitude may be decreased significantly, and averaging of a few (usu-ally not more than 3–10) MEP responses may be helpful in overcoming the poorsignal-to-noise ratio. High trial-to-trial variability of motor responses must betaken into consideration when deciding whether or not to perform averaging.

4.1.3.6 Signal

The typical muscle MEP is an oligophasic response of 10 µV to 10 mV ampli-tude, occurring 15–30 (35) ms post stimulus with a duration of 10–15 ms. Thelatency depends on the recording site and varies greatly between individuals.Both latency and amplitude are subject to strong fluctuations in anesthetizedpatients [121, 133]. In particular, with transcranial electrical stimulation, ampli-tudes tend to vary to an extent that may prevent true quantitative assessment.Latencies of responses are determined as the time of the first significant deflec-tion of the isoelectric line after stimulation. Amplitudes are usually measured ina peak-to-peak fashion as the difference between the most negative and the mostpositive component within one response. The duration of the response does notplay an important role in monitoring practice. Central motor conduction time,an important parameter in perioperative and intensive care unit diagnostics, isnot routinely measured in the operating room, since it complicates the record-ing procedure without adding much essential information.

4.2 PRINCIPLES OF CLINICAL APPLICATION

The literature on the application of MEP monitoring with supratentorial proce-dures remains sparse [20, 59, 72, 89, 102]. In fact, the method must still be con-sidered to be “in statu nascendi,” since only preliminary principles on how tointerpret intraoperative MEP data with this application are emerging. The con-siderations and observations outlined here are based on our own clinical expe-rience gathered with about 250 patients with supratentorial lesions. MEPmonitoring followed transcranial or direct motor cortex stimulation. MEPs canprovide direct information about the functional state of motor pathways.Although indirect conclusions about other brain regions can be drawn accord-ing to principles like local proximity and common vascular supply, the high sen-sitivity of MEPs to all kinds of interfering factors suggests a more specific use.Nevertheless, MEP monitoring can provide complementary information to SEPdata in most cases where SEP monitoring is performed.



4.2.1 Interpretation of MEPs and Practical Considerations

The relevant mMEP parameters are described in Section 4.1.3.2. There are nodefinite criteria for considering which MEP changes are significant for indicat-ing impairment in supratentorial lesions. Our practical experience in usingthem intraoperatively is described in following text. As with SEPs, normal fluc-tuations, technical conditions, the influence of systemic factors like anesthesia,and interindividual differences must be taken into consideration. According toour experience, the application of latency and amplitude criteria analogous tointerpretation of SEP findings leads to clinically useful conclusions. While alatency increase by 10% can be considered significant, an amplitude decreaseby less than 50% may be considered within acceptable range. The followingsemiquantitative relations seem to apply. Thus far, potential loss is most impor-tant: irreversible MEP loss is associated with permanent new postoperativemotor deficits, while preservation of MEPs denotes preserved motor function(Fig. 15.11).

FIGURE 15.11 Functional testing after placement of the test clip on a feeder in a patient with anAVM at the precentral sulcus. Upper extremity MEPs were recorded during removal of a left pre-central AVM. After induction of hypotension and application of a test clip on a major feeder, nosignificant changes of the parameters of the MEPs were recorded. This ruled out ischemia to themotor cortex and enabled the surgeon to proceed with this potentially hazardous procedure. Therewas no postoperative neurologic deficit.



Irreversible MEP alteration, or reversible loss or alteration, is associated witheither permanent or transient motor impairment, the former being rare withreversible MEP loss or alteration. Reversibility of MEP changes is usually dueto some surgical reaction to an early warning of MEP impairment. These prin-ciples differ from the current state of mMEP interpretation in spinal procedures[22, 123], resembling an all-or-nothing paradigm. Changes of MEP waveformare more difficult to assess objectively. However, dispersion phenomena withimpaired motor conduction may lead to a more polyphasic potential, whichmay therefore be interpreted as a warning sign. Central motor conduction time,routinely evaluated in preoperative and diagnostic MEP measurements, doesnot play a significant role in intraoperative MEPs. As a matter of fact, MEPlatency increase is rarely found without concomitant amplitude decrease, sothat isolated latency assessment is hardly ever necessary. Table 15.5 summa-rizes current principles of MEP interpretation. Figures 15.12–15.15 show typ-ical MEP behavior due to lesion resection or other surgical events.

MEP changes must be determined by comparing the most recent potentialwith some reasonable baseline measurement. A first baseline potential shouldbe obtained after induction of anesthesia, before the operation has started. How-ever, craniotomy and opening of the dura may lead to significant MEP changesbefore the actual intracranial procedure has started, so that it may be necessaryto update the baseline values. Nonsurgical factors such as fluctuation of anes-thesia or change in technical conditions (e.g., poorer electrode contact duringdirect cortical stimulation due to brain shift) may lead to intraoperative MEPchanges, necessitating the interpretation of further MEP changes with regard tothe latest state considered stable.

Analogous to SEP monitoring, bilateral MEP recording is mandatory withmidline lesions and desirable with lateralized approaches. However, bilateralrecording is usually only feasible with transcranial stimulation, since direct cor-tical stimulation requires exposure of the motor cortex.

TABLE 15.5 Correlation Between Cortically Evoked MEPs and Clinical Outcomea

MEP findings Clinical outcome (monitored limb)

Permanent new deficit Transient new deficit No new deficit

Irreversible loss always

Irreversible alteration frequently frequently rarely

Reversible loss rarely frequently frequently

Reversible alteration rarely frequently frequently

Unaltered always

aThis is a schematic summary presenting our long-standing experience in about 170 patients inwhom MEP monitoring was applied for supratentorial lesions and intraoperative MEP findingswere correlated with postoperative motor outcome.



MEPs should be recorded from both upper and lower extremities as well asfrom facial muscles, since motor deficit may occur in muscle groups or limbsnot monitored with otherwise stable MEPs. Given the usually limited numberof recording channels, the selection of recording sites depends on the specificsituation in a given patient. Some basic considerations are sketched in follow-ing text.

FIGURE 15.12 MEP loss due to overheating from an electrocoagulation instrument. Upperextremity MEPs were monitored during removal of a partially thrombosed postcentral-central AVM(Spetzler-Martin grade III) that had bled 2 weeks before, leading to a severe hemiparesis. Extensiveintraoperative use of bipolar coagulation during removal of the bleeding AVM led to transient MEPdeterioration and subsequent complete loss. At the end of the AVM resection, MEPs returned to thebaseline parameters. There was no postoperative increase in weakness, and the preoperative hemi-paresis slowly improved during follow-ups.



4.2.2 Specific Applications

4.2.2.1 Central Tumors and AVMs

The indication for MEP monitoring with central lesions adjacent to motorpathways is obvious. Direct motor cortex stimulation is performed via an elec-trode strip or grid. Figure 15.16 shows a typical case. Where to focus the record-ing depends on the exact location of the lesion. The more deeply seated thelesion, the more comprehensive a recording scheme is required. With a smallsuperficial lesion of the lateral frontal convexity, MEPs from the arm and facemuscles may be sufficient, while a frontomedial lesion will also require lowerextremity MEP recordings. Concomitant SEP recordings are seldom useful evenwith postcentral lesions, since resection will usually not be stopped because of SEPchanges with preserved MEPs.

In arteriovenous malformations (AVMs), motor tract monitoring is useful if theAVMs are located very close to the motor cortex or the motor tract. An exampleis found in temporomesial locations when the AVM encroaches on the brainstemand the tangle of vessels needs to be dissected from those vessels that encircle the

FIGURE 15.13 MEP loss due to vasospasm. MEPs were recorded from forearm flexor musclesduring resection of an insular glioma via a transsylvian approach. After tumor removal, a signifi-cant reduction (and eventually a complete disappearance) in MEP amplitude occurred. Warningwas given to the neurosurgeon. Papaverine was applied to the spastic sylvian vessels, and MEPsrecovered within 6 min.



brainstem and give off perforators through the basal surface of the brain. In thissituation, a test clipping of a vessel can be useful. The same holds during a dis-section of an AVM when the surgeon wants to temporarily exclude vascularbranches to the motor cortex. Lack of significant MEP and SEP changes helpssupport the surgeon in a dangerous step of dissection or sacrifice of a vessel. Inour experience, combined use of MEPs and SEPs can be helpful if the vascularmalformation is located close to the brainstem, underneath the insular cortex, orvery close to the central sulcus. In some occasions potential loss was observed dueto vasospasm, which could be reversed by the application of papaverine. In sev-eral instances SEPs or MEPs changed because of the systemic effects of low bloodpressure (BP). Significant lowering of mean arterial BP is a well-known aid inhandling the deep-seated, thin-walled vessels in the white matter at the deep apexof the AVM. Usually there are no changes at a mean BP of 60 mm Hg, but the com-bined effects of retraction, compression of the AVM toward the surrounding brain,and lowered BP can lead to MEP loss. Although the number of AVMs lying closeto the motor pathways is not high enough for a systematic evaluation of the results

FIGURE 15.14 Permanent MEP deterioration with permanent new paresis. Upper extremityMEPs were recorded during removal of a precentral malignant glioma. During resection, a signifi-cant MEP deterioration occurred without complete loss close to the posterior margin of the tumor.When a further MEP deterioration was indicated during removal of the posterior lesion wall, resec-tion was halted. There was a permanent new hemiparesis postoperatively.



of MEP monitoring, a number of rewarding observations support the notion thatmonitoring for AVMs may be very helpful in avoiding neurological deficits. Moreclinical perspectives and experiences are summarized in Section 6.

4.2.2.2 Insular Lesions

Insular tumors may extend deeply toward the basal ganglia and the internalcapsule [134]. The temporal part and, on the right side, the frontal part do notpose insurmountable problems. The greatest threat is posed by a tumor grow-ing beneath the M2 and M3 branches, which are covered by the frontal and tem-poral opercula, and the tumor has replaced the insular cortex, the claustrum,and the external capsule and has invaded the lateral putamen (especially itsmost dorsal extension). If the surgeon uses a transsylvian approach, all theseMCA branches have to be dissected away and the tumor resection has to pro-ceed beyond these arteries. One will also encounter the small perforating ves-sels that are supplying the lateral putamen and parts of the tumor. This is the

FIGURE 15.15 Permanent MEP deterioration with transient new deficit. Upper extremity MEPswere recorded during resection of a temporoinsular benign oligoastrocytoma invading the basalganglia. A significant MEP impairment occurred when the medial portion of the tumor was beingresected. Resection was stopped in this area. Postoperatively, there was a slight transient worsen-ing of the preoperative hemiparesis, which resolved completely until discharge.



most significant technical problem in the resection of insular gliomas, and, inour experience, MEP recording has been found to be useful in such cases. Itprovides a valuable criterion for proceeding with the resection, in particular ifintraoperative imaging is not available, as is the case in most neurosurgical cen-ters. Our experience with some 40 patients with insular tumors and MEP mon-itoring shows that maximum resection without significant postoperative motorimpairment is obtained if resection is stopped at the first signs of significantand persistent MEP deterioration (Fig. 15.17). Postoperative imaging typicallyreveals resection in the putamen close to the internal capsule, while slight tran-sient paresis may be found in the postoperative clinical evaluation. With insular

FIGURE 15.16 MEP deterioration that convinced the surgeon to stop a resection of a precentrallylocated tumor. Upper extremity MEPs were monitored during removal of a precentral low-gradeglioma that had partially invaded the precentral gyrus. Tumor resection was halted when MEPsdeteriorated during surgical approach to the motor strip. This led to full MEP recovery. Postoper-atively there was transient motor aphasia without paresis, corresponding to an incomplete supple-mentary motor area (SMA) syndrome. Postoperative MRI revealed the remains of the tumoranterior to and within the precentral gyrus.



lesions, the size and location of the craniotomy determine whether transcra-nially or cortically elicited MEPs are performed. In any case, a comprehensiverecording montage is advisable. SEP monitoring may also be useful with largelesions that require extensive dissection of sylvian vessels that are possibly sup-plying nonmotor parietal territories.

We have now had experience with well over 40 patients with insular tumorsmonitored with MEPs; the tumors included various types of astrocytic tumors.Nearly half of the patients had a tumor on the left side, and in about 40% ofthem, complete resection could be achieved as assessed on postoperative MRI.The policy of continuing the resection until significant changes of MEPs areobserved has proven to be extremely useful. Even transient MEP losses are

FIGURE 15.17 MEP loss indicating resection of tumor near the internal capsule. Upper extremityMEPs were recorded during resection of a grade II insular glioma extending deeply toward the inter-nal capsule. While the surgeon was working deep under the level of the insular cortex, MEPs wereimpaired, and resection was halted within this portion of the tumor. There was no new motordeficit postoperatively, and early postoperative MRI showed gross total (>90%) tumor resection,with the small dorsal portion of the tumor removed.



acceptable if surgery stops immediately. The likelihood of permanent deficits inthis group is less than 10%. The introduction of MEP monitoring was a strongsupporting element in our decision to develop a strategy for total resection ofhuge fronto-temporo-insular gliomas where the whole MCA tree frequently hasto be skeletonized. More clinical perspectives and experiences are summarizedon Sections 6.4 and 6.5.

4.2.2.3 Aneurysms

SEP monitoring does not pick up impending motor impairment in a certainproportion of aneurysms, obviously because of a poor sensitivity for subcorti-cal ischemia induced by compromise of perforating vessels (see Section 2) [13].At our institution, MEP monitoring in parallel with SEP monitoring has beenintroduced, and has proven useful in predicting postoperative subcorticalstroke with unchanged SEPs (Figs. 15.18 and 15.19). It is not yet clear, however,

FIGURE 15.18 Test occlusion of ICA with no change in the parameters of SEPs and MEPs. MEPsrecorded from the finger flexor and median nerve SEPs were monitored during clipping of a left ACIaneurysm. No changes in the parameters of the evoked potentials during test occlusion enabled thesurgeon to proceed with surgery.



whether MEP monitoring can reliably help to prevent such lesions, which seemto occur with inadvertent compromise of perforating arteries at dissection of theaneurysm. The dissection will be performed with maximum care anyway andperforators will be inspected. They may appear open but kinked, and the com-promised flow through these small vessels may be irreversible even if it is notdue to placement of the clip (e.g., by vasospasm).

Given the more basal location of the craniotomy usually required foraneurysm surgery, MEPs are usually elicited by transcranial electrical stimu-lation. Recording MEPs from the upper extremities and face muscles may be

FIGURE 15.19 New motor deficit from subcortical stroke following perforator manipulationreflected by transient MEP loss and subsequent MEP deterioration despite stable SEPs. Thenar MEPsand median nerve SEPs were recorded during dissection and clipping of an aneurysm of the basi-lar artery and superior cerebellar artery and a posterior communicating artery (PCOM) infundibu-lum via a common pterional approach. MEP impairment with no changes in the parameters of SEPsoccurred during manipulation of perforators from the PCOM. Postoperatively, the patient experi-enced a new slight hemiparesis, and brain CT scans revealed a small basal ganglia infarction.



sufficient for vertebral basilar artery and MCA aneurysms. In surgery for ICAand ACA aneurysms, lower extremity SEPs are more important than lowerextremity MEPs which are more difficult to elicit. Cortical ischemia seems to bereliably picked up by SEP monitoring.

The perforating arteries branching from the ACA (e.g., the Heubner’s recur-rent artery) supply motor pathways, including corticonuclear efferents andfibers descending toward cervical motoneurons. Thus, if lower extremity MEPscannot be reliably obtained with ACA aneurysms, or exceedingly strong muscletwitches incompatible with microsurgical dissection would be unavoidable, onemay switch to the more readily recordable hand MEPs. A summary of clinicalaspects and limitations is given in Sections 6.1 and 6.2.

5 SAFETY AND ANESTHESIA

5.1 SAFETY

Neurophysiological monitoring, when properly performed with reliably func-tioning equipment and according to the technical standards described in thesechapters, does not seem to carry significant health risks to the patient. Theplacement of subdermal needle electrodes in a sterile manner for stimulation orrecording has never been associated with inflammation or severe bleeding inour experience with over 1500 patients monitored intraoperatively. The onlyadverse effect is slight local venous bleeding after removal of the needle elec-trodes in some cases. The use of electrical equipment and the application of cur-rent for stimulation purposes requires optical grounding of all patient contactsand thorough grounding of the patient to prevent inadvertent current flow.

5.1.1 SEP Monitoring

This type of monitoring requires almost continuous stimulation, often for sev-eral hours at a relatively strong intensity (as compared with the SEP eliciting inawake patients). This has never led to adverse effects in a series of over 900monitored patients at our institution. Muscle twitching induced by peripheralnerve stimulation in nonrelaxed patients does not seem to cause postoperativeconsequences and rarely interferes with microsurgical dissection.

5.1.2 Motor Mapping and Monitoring

The main concern with high-voltage electric pulses applied to the brain isexcessive charge density, charge per phase, and “damage threshold” values forneural injury that have been deduced from animal models [126, 135]. It hasbeen argued that electrical stimulation for eliciting MEPs, presented in Section 4,



meets the limits set by these conservative criteria [96]. Conversely, the sus-tained repetitive stimulation at 50–60 Hz via bipolar ball-tip stimulators (Penfield’stechnique) may exceed those limits by many thousand of times [71, 77, 88]. Asa matter of fact, no neural damage has been found in well over 350 cases ofdirect cortical or transcranial stimulation performed at our institution, or inother large series of transcranial MEP monitoring [22, 107, 125]. Even with themuch more aggressive exposed cortex bipolar stimulation method (Penfield’stechnique), no neural injury has been reported [68, 71, 74, 75, 77, 88, 90–95].However, the release of gas bubbles has been observed in animal experimentswith only a slight modification of the method (rectified stimuli) [68]. With thebipolar stimulation method (Penfield’s technique), overt seizures (tonic move-ment beyond stimulation) were found in 11% of cases in a recently publishedseries [93] and prolonged EMG activity after stimulation in another 14%. Theconcern, however, that the method may induce epilepsy by some kind of kin-dling effect [136] has not been confirmed. Conversely, epileptogenicity of theMEP stimulation method is very low because of the high-frequency trains,which have a lower tendency to trigger autonomous cortical circuitry than fre-quencies around 50 Hz. An additional factor is the length of the train: 25 ms inthe MEP stimulation method versus 3–4 s in Penfield’s technique using 50 Hzstimulation. In our experience with both direct cortical and transcranial elec-trical stimulation using a short train of stimuli, intraoperative seizures areinduced or facilitated in very rare cases (below 1%) that require immediateapplication of neuromuscular block or barbiturates. Other adverse effects thatcan potentially interfere with the ongoing microsurgical procedure includestrong muscle twitching by inadvertent activation of back muscles. Sometimesthis requires a brief halt in monitoring during the lesion dissection.

5.2 ANESTHESIA

SEP and MEP amplitudes, waveforms, and latencies are affected by various sys-temic factors, including body temperature, blood pressure, blood oxygenation,and PaCO2 [137, 138]. Although the effects can be significant, careful preser-vation of homeostasis by the anesthesiologist and the surgeon will minimizesuch influences. On the contrary, the effects of anesthestics may be more dis-crete in some cases, but they obviously cannot be eliminated and must be takeninto consideration with intraoperative evoked potential (EP) assessment.Latency or amplitude alterations occurring with fluctuations in the depth ofanesthesia may mask or simulate changes induced by surgical events. This maylead to false-negative or false-positive interpretations of the neurophysiologicalsignals. The effects of anesthesia will often be more prominent with preexistingEP alterations (e.g., due to neural damage) or with more difficult recording



conditions (e.g., with lower extremity SEPs or MEPs). Coordination with theneuroanesthesiological team should be established. In addition to sharing detailsabout anesthesia in a given case, the surgeon often has to guide the anesthesiol-ogist with regard to the anesthetic regimen. This method should be discussedwith the anesthesiologist to obtain optimal anesthesia for the patient.

5.2.1 Anesthesia for Motor Cortex Mapping and MEP Monitoring

5.2.1.1 MEPs

Homeostasis and adequate anesthesia are of paramount importance withmuscle MEP monitoring. The great importance of anesthesia for successful EPrecording is attested to by the fact that a whole chapter (Chapter 17) is devotedto this subject. Here, we will restrict ourselves to some basic descriptionsregarding MEPs. Muscle MEP monitoring is mainly hampered by the inhibitoryeffects of general anesthesia at the corticomotoneuronal junction. Although theshort train stimulation paradigm has led to a major improvement in elicitingMEPs in terms of stability and overall recordability, the anesthetic regimen stillexerts great influence on MEP properties (e.g., signal-to-noise ratio and trial-to-trial variability). Since semiquantitative evaluation of responses is helpful insupratentorial MEP monitoring, amplitude stability is a major issue. Total intra-venous anesthesia with propofol and opioids has proven suitable and is appliedin many institutions that perform MEP monitoring [123, 125, 139]. Volatileanesthetics, in particular halogenated agents, may have a stronger depressanteffect on motor responses and are therefore avoided with MEP monitoringwhen possible [139]. In practice, however, MEP monitoring is usually still pos-sible under inhalational anesthesia if total intervenous anesthetic (TIVA) use isnot feasible. The greater variability of responses must be taken into considera-tion when interpreting intraoperative changes. Partial neuromuscular blockadeadds to the variability of MEP responses but may still preserve recordability[140]. Although relaxation should be avoided with MEP monitoring to obtainoptimum recording conditions, the muscle twitching may be so disturbing thatonly a partial neuromuscular block will enable continued parallel MEP moni-toring and microsurgery. In our experience, a blockade of up to two responsesin the train-of-four paradigm is compatible with MEP monitoring. This corre-sponds to the findings of other groups [140, 141].

5.2.1.2 Bipolar Cortex Stimulation Technique (Penfield’s technique)

The compatibility of mapping the exposed motor cortex using the bipolarstimulation method in the presence of anesthesia has not been formally tested.However, it has proven compatible with an anesthetic regimen including



nitrous oxide, isoflurane, fentanyl, and propofol [93]. To reliably pick up move-ment or EMG motor responses, relaxation cannot be applied during the map-ping procedure. Even residual relaxation after intubation should be excludedto avoid false-negative responses when trying to identify motor cortex areas.

6 VALUE AND LIMITATIONS FROM A CLINICAL PERSPECTIVE

For all neurosurgical groups that have been involved with SEP monitoring—such as ours—the advent of reliable motor tract monitoring has been a long-awaited event. MEP monitoring has been possible on a routine basis for about7 years now and has been applied not only for aneurysm surgeries but also forcentrally located gliomas, centrally located AVMs, insular gliomas, difficult-to-access cavernomas, deep-seated metastases (if not treated by Gamma-knife),and lesions in the midbrain. Simultaneous monitoring of MEPs and SEPs wasfound to be a valuable addition to the armamentarium that is available inmodern microneurosurgery. This section summarizes our experience with 250supratentorial surgeries monitored with MEPs.

6.1 ANEURYSMS

Many experienced surgeons do not believe that there is a need to monitoraneurysms with SEPs, let alone with MEPs. Is it worthwhile to perform bothmethods and increase the expense of monitoring 100 patients to avoid one ortwo hemipareses? In our experiences, it is. In our first publication on ane-urysms and monitoring with SEPs, we concluded that monitoring should bedone in larger lobulated or complicated aneurysms of the anterior circulation[15]. We still believe that this is true. All neurosurgeons who have startedaneurysm surgery during the last 10 years in our service have chosen to use thismodality whenever it was available. In certain aneurysms, such as very largeones in the MCA bifurcation or large aneurysms of the carotid bifurcation or ofthe PCOM, we would delay surgery if monitoring was not available (even formore than a day if it was elective surgery). Such has become the attitude of theneurovascular fellows in our group. Small MCA aneurysms, especially if theyhave not been bleeding, can be done without monitoring. Aneurysms of thebasilar tip or at the origin of the superior cerebellar artery (SCA) need to bedone with simultaneous monitoring of SEPs and MEPs. We have currently gath-ered experience with about 60 aneurysms using simultaneous SEP and MEPmonitoring, since SEPs alone would be unreliable. It was found that if new



motor deficits occurred that had not been detected with the SEPs and could bereconstructed after the surgery from postoperative MRI or CT, small perforat-ing vessels usually accounted for those insults that led to MEP deteriorationduring surgery or shortly after it. Obviously, the avoidance of all motor defectsfrom surgery is the aim. But some of these defects were obviously due tovasospasm or to the insufficient flow in a seemingly unaffected or only mildlydistorted perforating vessel. Thus MEP monitoring helps more than SEP mon-itoring alone, but it cannot prevent all motor deficits.

Although no formal evaluation has yet taken place, a number of cases inwhich clips were reapplied or the course of surgery was influenced by motortract monitoring appear to be similar to the experience with SEP monitoring. Itis an interesting experience in aneurysm surgery when one observes potentialloss, inspects the situs, and suddenly detects the kinking of a perforator 2–3 mmbeyond the tip of the clip due to indirect traction exerted by tension on anarachnoid string. The use of intraoperative ultrasound is easily possible onbranches such as M2 or the carotid main trunk. However, it can be impossiblefor the smaller perforators, especially if they are obstructed from view or cov-ered by the bulk of the aneurysm.

6.2 ANEURYSMS—SUMMARY

The absence or presence of SEP changes following surgical maneuvers may beequally useful indicators. SEP changes led to a modification in surgical strat-egy in 8.1% of patients in whom SEP changes were monitored. Surgical reac-tion consisted of removing offending traction, removing temporary vesselclips, replacing aneurysm clips, and elevating blood pressure [16]. Whereas inthe past aneurysms were only monitored with SEPs, complicated aneurysmshave now been simultaneously monitored using MEPs and SEPs in over 60patients. The most important difference from single-modality SEP monitoringwas the increased detection of motor impairment stemming from manipula-tion of small perforators. Not all these motor deficits could be reversed by thesurgeon’s reaction, but there are reasons beyond the immediate capability ofthe surgeon to rectify them. The fact that not all motor deficits can be avoidedshould not be taken as a serious argument against motor tract monitoring,since every motor deficit avoided is worth the effort. We observed that neces-sary narrowing of an M2 branch with reduced flow confirmed by intraopera-tive ultrasound testing could be accepted since the functional monitoring withMEPs and SEPs did not show changes. Neurophysiological monitoring wasthus helpful in deciding which degree of narrowing was acceptable and whichwas not.



6.3 AVMS—SUMMARY (SEE ALSO SECTION 2.2.2.2)

Over 30 AVMs and over 30 patients with cerebral cavernomas have been mon-itored. In vascular surgery the absence of changes is as important as changes orthe disappearance of the potentials. Test clipping without changes in evokedpotentials can be of significant reassurance for the surgeon and thus help inspeeding up the procedure. In addition, systemic factors such as arterial bloodpressure that may play a more important role than in tumor cases can also beassessed. With many vascularly induced changes, reversibility can be achieved.Therefore, monitoring in patients with vascular pathology appears to be par-ticularly helpful.

6.4 CENTRALLY LOCATED TUMORS

Centrally located tumors provide particular problems: The normal geometrymay be distorted to such a degree that it is impossible to even guess whetherthe motor cortex has been pushed backward or anteriorly or whether it is lyingunderneath the lesion. In patients with cavernomas, it may be of the utmostimportance to detect precisely whether the motor tract fibers convergingtoward the knee of the internal capsule are being pushed anteriorly or poste-riorly by the lesion. Intraoperative use of the phase reversal technique or extra-operative mapping with a grid has been found to be helpful in planning theapproach (either more anteriorly or posteriorly) as well as for guidance duringthe resection. The same has been found true for gliomas lying superficially oron the mesial hemispheric cortex. Even if the surgeon thinks he or she is stay-ing strictly within the tumor, he or she can reach the healthy surroundingtissue and unknowingly affect the motor tracts. Because removal of tumortissue is indirectly exerting traction forces on the surrounding healthy brain,MEP or SEP alterations may occur shortly before one reaches the motor fibers.Particularly dangerous is a situation where one reaches a sulcus 2 or 2.5 cmbelow the surface with the chance of injuring a vessel that supplies the motorcortex.

In our experience, it has been impossible to avoid all new motor deficits, andin a strict scientific way we have not even tried to ensure that the rate of newmotor deficits is lower with monitoring compared to surgery without monitor-ing. In essence, the number of amplitude deteriorations and complete potentiallosses that have been observed have convinced us that monitoring of MEPs isuseful.

This is particularly true for insular gliomas. No insular glioma will be oper-ated on without monitoring. The schematic relationship given in Table 15.5has thus far been consistent. If some evoked potentials remain at the end of



surgery, then there is a very good chance that the motor deficit is either notpresent or, if it has been present, it will recover. It remains more doubtfulwhether MEP monitoring is necessary with meningeomas bulging into the brainsubstance. It may help with the preservation of ACA branches that have beenpushed away by the meningeoma, but usually the dissection of the borderbetween meningeoma and brain is not so difficult. In insular gliomas we haverepeatedly seen cases where vasospasm led to loss of potentials and recoveryfollowing application of papaverine. We are convinced that the removal oflarge type B insular gliomas would have been associated with a much highermorbidity than in our previously published paper [134]. Since that study wehave altered our strategy and no longer operate on grade IV gliomas in olderpatients. With this new policy the incidence of motor deficits has decreasedsignificantly, and it appears that the use of MEP monitoring has contributedto this. We continue the resection following the outline of the tumor (nowwith the use of a neuronavigation system) as long as there is no significantreduction in amplitude of evoked potentials and as long as there is no loss ofthe potentials (even in the deeper sections of the tumor cavity). If loss ofpotentials occurs, we apply papaverine to the vessels and wait a certain amountof time. If there is no recovery (making it a transient loss), resection is stopped.We frequently find the posterior part (2–3 cm) of the insular cortex infiltratedby the tumor left behind.

Encouraged by our experiences with surgery for drug-resistant epilepsy, incertain centrally located gliomas without drug-resistant epilepsy we havestarted to apply preoperative mapping of motor, sensory, and speech function.In these cases the procedure is explained to the patient, and if he or she agreesto the second procedure of grid implantation, one can approach the tumor witha precise map of functional areas as it relays to the cortical surface. Transposi-tion of the map is facilitated by the use of digital photography of the brain sur-face before and after grid application.

In benign lesions, such as cavernomas, MEP and SEP monitoring is used ifthe lesions are close to the motor tract. These cases are rare, but they haveoccurred, and MEP and SEP monitoring was able to provide good feedback tothe surgeon. Therefore, the general attitude in our department is that benigntumors should not be removed without combined MEP and SEP monitoring.An interesting case has been published of a midbrain cavernoma that wasapproached through a transventricular subforniceal approach and was removedwith monitoring of MEPs and SEPs. Obviously, brainstem cavernomas are alsomonitored with both modalities [142].

With approximately 350 MEP monitoring cases, including spinal surgeriesand infratentorial surgeries, we have gained enough experience to develop afeeling for the application of MEP monitoring and for criteria for reacting toMEP changes.



6.5 CENTRALLY LOCATED TUMORS—SUMMARY

Neurophysiological mapping has corrected the presurgical estimation of the cen-tral sulcus location in 12% of the patients. It also helps identify the motor stim-ulation point for monitoring MEPs. In a series of 140 operations for central andinsular lesions, most cases being gliomas and a minority being meningiomas,metastases, and other lesions, important observations could be made. In the vastmajority of patients operated on, there were no new motor deficits. Many newdeficits were related to supplementary motor area syndrome; thus they weretotally reversible. Of the permanent new deficits, around 10% were severe, andaround 29% occurred in muscle groups that were not included in the monitor-ing setup. Therefore, if only monitored muscle groups or limbs are considered,only about 9% new permanent deficits were observed in this group of central andinsular space-occupying lesions. Considering the MEP results in this group, 58%had no significant change in potentials. In the group without significant changes,continuously stable potentials were seen in 75%, the rest showing only variationsin amplitude. In the group with significant changes, irreversible loss occurred in9% of the patients and reversible loss in 17%. The rest were reversible or irre-versible alteration of potentials only. Of the group with reversible potential loss,permanent deficits occurred in only 10% of patients and transient deficits in45%. In all patients in which irreversible MEP loss occurred, however, long last-ing new motor deficits were observed postoperatively. In one third of cases withirreversible MEP alterations, transient deficits occurred, but permanent deficitswere more frequent in this group (see Table 15.5).

ACKNOWLEDGMENTS

We thank M. Kurthen, M.D., Department of Epileptology, Bonn, for help withthe section on the extraoperative mapping technique in epilepsy, and U. Pechstein,M.D., for his help in designing some figures while he was a coworker in themonitoring group in Bonn. Thanks also to all former coworkers from the Bonnmonitoring group: M. Taniguchi, M.D.; U. Pechstein, M.D.; J. Zentner, M.D.;and C. Cedzich, M.D.

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C H A P T E R 16

NeurophysiologicalMonitoring DuringNeurosurgery forMovement DisordersJAY L. SHILS

Division of Intraoperative Neurophysiology and Department of Neurosurgery, Hyman-NewmanInstitute for Neurology and Neurosurgery, Beth Israel Medical Center, New York

MICHELE TAGLIATI

Department of Neurology, Beth Israel Medical Center, New York

RON L. ALTERMAN

Department of Neurosurgery, Hyman-Newman Institute for Neurology and Neurosurgery, Beth Israel Medical Center, New York

1 Introduction2 History and Theory

2.1 Historical Notes2.2 Theoretical Basis for Surgery in the Basal Ganglia2.3 Modern Movement Disorder Surgery: General Overview

3 Operating Room Environment and Basic Equipment3.1 Operating Room3.2 Recording Electrodes3.3 Amplification3.4 Stimulation

4 Technique for Movement Disorder Surgery4.1 General Stereotactic Technique


ABSTRACT

During stereotactic procedures for the treatment of medically refractory movement dis-orders, intraoperative neurophysiology shifts its focus from simply monitoring the effectsof surgery to actually guiding the surgeon’s actions. The small size, poor visualization,and physiological nature of these deep brain targets compel the surgeon to rely on some



406 Jay L. Shils, Michele Tagliati, and Ron L. Alterman

form of physiological confirmation of proper anatomical targeting, whether a neuroablativeor deep brain stimulation procedure is being performed. This chapter reviews the historyof movement disorder surgery; the current physiological rationale for surgical interven-tion in cases of medically refractory Parkinson’s disease, dystonia, and essential tremor;and the various neurophysiological monitoring methods employed during these so-calledfunctional neurosurgical procedures. Finally, the authors discuss the most common surg-eries currently employed and detail their preferred surgical techniques.

1 INTRODUCTION

The full potential of intraoperative neurophysiology is realized during the perfor-mance of so-called functional neurosurgical procedures. During these interventionstherapeutic lesions or stimulating electrodes are stereotactically placed within deepbrain structures to treat movement disorders such as Parkinson’s disease (PD),essential tremor (ET), dystonia, affective disorders, and chronic neuropathic pain.

The deep location of these structures precludes direct surgical approaches.Instead, surgeons rely on a combination of image-guided stereotactic techniquesand intraoperative neurophysiology to place the therapeutic lesions or stimulatingelectrodes with acceptable accuracy and safety. Unlike tumors, which are relativelylarge and easily identified on CT or MRI, functional neurosurgical targets typicallyare small and poorly visualized with current imaging modalities. Moreover, becausethese are physiologic as much as anatomic targets, image-based targeting mayincompletely identify the desired location. Consequently, intraoperative recordingand stimulation techniques have been developed to aid target localization. Thesetechniques complement anatomical targeting by providing real-time electrophysi-ological data concerning probe position and the surgical target. The surgeon andphysiologist use these data to “fine-tune” their anatomic targeting before complet-ing the therapeutic intervention. Thus employed, intraoperative neurophysiologydoes not simply monitor surgical activity; it guides it.

In this chapter, we provide an historic overview of intraoperative monitoringfor movement disorder surgery and a detailed account of our approach to thesesurgeries, which has evolved over the course of more than 500 interventions.

2 HISTORY AND THEORY

2.1 HISTORICAL NOTES

2.1.1 Surgery for Movement Disorders

Sir Victor Horsely is reported to have performed the first neurosurgical pro-cedure for a movement disorder when, in the late 1800s, he resected part ofthe precentral gyrus in a patient with athetoid movements. The surgery haltedthe abnormal movements but caused dyspraxia and paralysis of the limb [1].


Neurophysiological Monitoring During Neurosurgery for Movement Disorders 407Neurophysiological Monitoring During Neurosurgery for Movement Disorders 407

The first successful basal ganglia surgery is credited to Meyers [2–4], whoreported improvement in a patient with postencephalitic parkinsonism in 1939.Prior to this landmark report, surgery within the basal ganglia was avoidedbecause it was believed that human consciousness resided in these structures.Despite the high mortality rates (10–12%) that plagued these “open” proce-dures (i.e., via craniotomy) [2–5], Meyers demonstrated the potential benefitsof basal ganglia surgery and opened the door for the application of less invasivestereotactic approaches to these deep brain structures. He also provided thefirst accounts of human basal ganglia physiology, describing the frequency,phase, and amplitude of neuronal signals from the striatum, pallidum, corpuscallosum, internal capsule, subcallosal bundle, and dorsal thalamus in patientswith and without movement disorders [3, 4, 6]. Meyers quickly realized thepotential value of the accumulated data, which he ultimately employed to helplocalize specific deep brain structures during movement disorder surgery.

Robert Clarke designed the first stereotactic frame in 1908 [7]. His frameemployed skull landmarks to target deep brain structures in small animals, atechnique that could not be translated to clinical use because of the more variedand complex shape of the human skull and brain. Consequently, it was notuntil 1947, after the introduction of ventriculography, that Spiegel and Wycisperformed the first human stereotactic surgeries, for psychiatric illness [8] andHuntington’s chorea [9]. In following years a number of human stereotacticatlases were published, and standard meridia (e.g., the intercommissural line)from which stereotactic coordinates could be determined were established.

Effective targets for stereotactically guided neuroablation were discoveredempirically. For example, Cooper stumbled upon the beneficial effects ofglobus pallidus lesioning by accidentally ligating the anterior choroidal arteryof a PD patient [10] while performing a pedunculotomy. He later adoptedstereotactic approaches to pallidal lesioning, reporting favorable results andreduced surgical mortality rates (∼3%) as compared to open procedures[11–14]. Laitinen described how Leksell further improved the results of palli-dotomy by placing the lesion more posteriorly and ventrally within the inter-nal segment of the globus pallidus (GPi) [15], that portion of the nucleus thatwe now know is responsible for sensorimotor processing [16, 17]. In 1963,Spiegel et al. [18] described campotomy, in which the fibers of the pallidofu-gal, rubrothalamic, corticofugal, and hypothalamofugal pathways are inter-rupted within the H fields of Forel. They reported promising results in25 patients with tremor and 25 with rigidity. In the end, however, thalamo-tomy emerged as the most commonly performed movement disorder proce-dure in the pre-levodopa era because of the consistent tremor control itprovided. Though most surgery for PD ceased after the introduction of lev-odopa in 1967, small numbers of thalamotomies were performed for medicallyrefractory tremor during the next 25 years, until the reintroduction of Leksell’spallidotomy by Laitinen et al. in 1992 [15].



2.1.2 Neurophysiology and Movement Disorder Surgery

Most early electrophysiologic studies of the human thalamus and basal gangliawere performed with macroelectrode techniques that yielded relatively crude,EEG-like responses [19–23]. Electrodes and recording techniques were refinedover subsequent decades, culminating in the development of single-cell micro-electrode recording. Of note is the work of Albe-Fessard, who refined micro-electrode techniques for experimental purposes and paved the way for theirintraoperative use [24, 25]. It was her belief that micro-electrode recording(MER) would “provide a powerful tool in improving stereotactic localizationand that it would furthermore reduce the risk due to anatomical variability”[25]. In recent years, Madame Albe-Fessard’s vision has been realized as MERhas gained in popularity and ready-to-use recording systems have become com-mercially available.

The history of electrical brain stimulation begins with Fritsch and Hitzig,who in 1870 elicited limb movement in dogs by stimulating the frontal cortex,and then defined the limits of the motor area electrophysiologically [26]. Intra-operative cortical stimulation studies by Penfield and colleagues from the late1920s through the late 1940s contributed seminal information concerning thesomatotopic organization of the cerebral cortex by defining the motor and sen-sory “homunculi.” In 1950, Spiegel et al. described the use of stimulationduring surgery at the H fields of Forel to both “test the position of the electrodeand to avoid proximity to the corticospinal pathways ventrally, the sensorythalamic-relay nuclei dorsally, and the third nucleus posteriorly” [18].

Other neurophysiological techniques, such as impedance monitoring [20,27, 28] and evoked potential recordings [29–33] also have been employed aslocalization tools; however, these techniques serve predominantly as adjunctsto recording and stimulation.

Perhaps the most significant advance in functional neurosurgery in the lastdecade has been the introduction of chronic electrical stimulation (termed“deep brain stimulation” or DBS) as a therapeutic alternative to neuroablation.Deep brain stimulation provides three potential advantages when compared toneuroablation:

1. DBS is reversible. If stimulation induces an unwanted side-effect, onesimply turns the stimulator off or adjusts parameters. Thus the risk ofpermanent adverse neurological events is reduced.

2. Stimulation parameters may be customized to each patient, potentiallyenhancing therapeutic efficacy.

3. Access to the surgical target is maintained via the implanted electrodeand programmable pulse generator. Therefore, therapy may be modifiedover time through simple stimulation adjustments, potentiallyincreasing the longevity of response.


Neurophysiological Monitoring During Neurosurgery for Movement Disorders 409

Thus far, two studies that compared thalamic DBS to thalamotomy for thetreatment of tremor have been published. Both studies found DBS to be thesuperior treatment modality in large part because of the ability to adjust stim-ulation parameters in the event of symptom recurrence.

Presently, movement disorder surgery is focused on three structures: theventrolateral (VL) nucleus of the thalamus, the globus pallidus pars internus(GPi), and the subthalamic nucleus (STN) (Fig. 16.1) (see also color plate).Each of these structures can be targeted for ablation in procedures that are,respectively, termed thalamotomy [26, 34–47], pallidotomy [18, 33, 39, 46,48–86], and subthalamotomy [87, 88]. Alternatively, each can be targeted forchronic electrical stimulation [33, 47, 52, 77, 89–115]. The choice of targetis based largely on clinical diagnosis and the symptoms to be treated. Theinterested reader is directed to a detailed account of our patient and targetselection criteria [116].

FIGURE 16.1 A three-dimensional artist’s rendition of the structures involved in surgery formovement disorders. The light greenish blue structure on the left is the globus pallidus (GPi andGPe). The large grey structure on the right is the thalamus, and the small dark green structure isthe subthalamic nuclei (STN). The medial edge of the STN is only 6.0 mm from the midline of thebrain. With the trajectories that our group uses in the operating room, we encounter around10.0 mm of GPi, 11.0 mm of VIM, and 5.0 mm of STN. Modified from [117] (see also color plate).



2.2 THEORETICAL BASIS FOR SURGERY

IN THE BASAL GANGLIA

Our current understanding of the functional organization of the basal gangliaand PD pathophysiology is based predominantly on data derived from the studyof primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-inducedParkinsonism [118–123]. Microelectrode techniques also have contributedgreatly to this body of knowledge. Though incomplete, the current model ofbasal ganglia function is partly responsible for the rebirth of movement disor-der surgery, providing a scientific basis for selecting those deep brain structuresthat are currently targeted for therapeutic interventions.

The model is depicted in Fig. 16.2. The basal ganglia are composed of two prin-cipal input structures (the corpus striatum and the STN), two output structures(GPi and substantia nigra pars reticulata [SNr]), and two intrinsic nuclei (exter-nal segment of the globus pallidus [GPe] and substantia nigra pars compacta [SNc])[124]. Five parallel basal ganglia-thalamo-cortical circuits (motor, oculomotor,

FIGURE 16.2 Diagrammatic representation of the basal ganglia circuit, showing the direct andindirect pathways proposed by DeLong and colleagues [121, 122]. The light grey lines representexcitatory pathways, and the darker lines show inhibitory pathways.



two prefrontal, and limbic) have been described [123]. While surgical interventionstarget the motor circuit, it is likely that lesioning and stimulation also impact othercircuits as well.

The corpus striatum, which is composed of the caudate and putamen, is thelargest nuclear complex of the basal ganglia. The striatum receives excitatory(glutamatergic) input from several areas of the cerebral cortex as well asinhibitory input from the dopaminergic cells of the SNc. Cortical and nigralinputs are received via the “spiny” neurons. One subset of these cells projectsdirectly to the GPi, forming the “direct pathway,” while another subset pro-jects to the GPe, the first relay station of a complementary “indirect pathway,”that passes through the STN before terminating at GPi. The antagonisticactions of the direct and indirect pathways regulate the neuronal activity ofGPi, which, in turn, provides inhibitory input to the pedunculopontinenucleus (PPN) and the VL nucleus of the thalamus. The VL nucleus projectsback to the primary and supplementary motor areas [125, 126], completingthe cortico-ganglio-thalamo-cortical loop. The direct pathway inhibits GPi,resulting in a net disinhibition of the motor thalamus and facilitation of thethalamo-cortical projections. The indirect pathway, via its serial connections,provides excitatory input to the GPi, inhibiting the thalamo-cortical motorpathway.

In PD, loss of dopaminergic input to the striatum leads to a functional reduc-tion of direct pathway activity and a facilitation of the indirect pathway. Thesechanges result in a net increase in GPi excitation and a concomitant hyperinhi-bition of the motor thalamus. The excessive inhibitory outflow from GPireduces the thalamic output to supplementary motor areas that are critical tothe normal execution of movement.

This model accounts well for the negative symptoms of PD (i.e., rigidity andbradykinesia) and supports both GPi and STN as rational targets for surgicallytreating PD. The model is incomplete, however, because it does not fullyaccount for hyperkinetic features of PD such as tremor and levodopa-induceddyskinesias, physiological phenomena that are poorly understood.

Tremor activity is consistently detected in the VL nucleus of patients withPD or ET, and the VL nucleus continues to be the primary surgical target fortreating medically refractory tremor. However, it is unclear if the motor thala-mus is the primary generator of tremor activity or merely participates in thetransmission of tremor-generating signals. Moreover, the evidence that bothpallidotomy [52, 60] and STN DBS [96] also control parkinsonian tremor sug-gests that intervention at many points within the tremor-generating loop maysuppress this symptom.

Levodopa-induced dyskinesias (LIDs) are involuntary movements of the limbsor trunk that are temporally associated with levodopa administration [127, 128].



These movements are typically choreiform or dystonic in nature and are easilydistinguished from the tremor of PD. Pharmacodynamic factors related tochronic exogenous dopaminergic stimulation probably play a fundamental rolein levodopa-induced dyskinesia. According to the model, pallidotomy shouldworsen LID by reducing pallidal inhibition of the VL nucleus, a hypothesis thatis supported by the experimental observation that STN lesions, which reducethe excitatory output from STN to GPi, cause dyskinesias in primates that areindistinguishable from LID [129]. On the contrary, LID is the most respon-sive symptom to pallidotomy, a consistently observed phenomenon [130]. Ithas been hypothesized that sensitization of dopamine receptors by exogenouslyadministered levodopa may cause aberrant neuronal firing patterns with con-sequent disruption of the normal flow of information to the thalamus and thecortical motor areas [131]. It follows that pallidotomy may improve LID by dis-rupting this aberrant flow.

2.3 MODERN MOVEMENT DISORDER SURGERY:GENERAL OVERVIEW

There is no one best method for performing movement disorder surgery.Rather, stereotactic surgeons modify general approaches to target localizationto suit their personal preferences and to take advantage of their institution’sstrengths. Currently accepted technique involves frame-based anatomical local-ization supported by intraoperative physiological confirmation of proper tar-geting. An overview of the various anatomic and physiologic techniquescurrently in use follows.

2.3.1 Anatomical Targeting Techniques

In the pre-levodopa era, positive contrast and air ventriculography wereemployed to localize the foramen of Monro and the anterior and posteriorcommissures. The stereotactic coordinates of therapeutic targets were thendetermined [98, 132] based on their relationship to these structures as describedin various stereotactic atlases. Targeting accuracy was therefore limited by theinaccuracies of these atlases, which were typically generated from just one ora few specimens whose true dimensions were distorted by formalin fixationand by anatomical distortions created by the intraventricular injection of airor contrast. Today, CT- and MRI-based techniques, which demonstrate thebrain parenchyma noninvasively, have supplanted ventriculography as theprimary means of anatomically localizing stereotactic targets. Nevertheless,



ventriculography is still employed by many stereotactic surgeons and thereforeremains an important technique.

The introduction of CT [133] revolutionized the diagnosis and treatment ofneurologic diseases and encouraged changes in stereotactic frame design,expanding the uses of frame-based stereotaxis to include tumor biopsy andresection [134, 135]. Soon after the introduction of MRI, Leksell et al. [136]demonstrated its applicability to stereotactic systems. MRI provides superiorresolution as compared to CT, as well as multiplanar images [137, 138] withminimal frame-related artifact [137]. Nonreformatted MRI beautifully demon-strates the commissures, the thalamus, and most basal ganglia structures [138].These features permit direct stereotactic localization of the surgical target insome instances [104, 139–143]; however, indirect targeting, based on accuratelocalization of the commissures, may still yield the most reliable target coordi-nates [143].

The most significant drawback to targeting with MRI is the potential forimage distortion introduced by nonlinearities within the magnetic field [144].Distortions can be generated by a number of factors, including the presence offerromagnetic objects within the field, imperfections in the scanner’s magnets,and, most commonly, patient movement [138, 144, 145]. Walton et al. demon-strated that targeting errors are greater in the periphery than in the center of themagnetic field and stereotactic space [146, 147]. MRI distortion may also berelated to the pulse sequence(s) employed. For example, it has been suggestedthat fast spin-echo inversion recovery sequences resist imaging distortions sec-ondary to magnetic susceptibility better than other image acquisition methods[148, 149].

In contrast to MRI, CT maintains linear accuracy, thereby reducing image-induced targeting errors [138, 150]. However, metallic artifact can impede visu-alization of the commissures, CT tissue resolution is inferior to MRI, and axialimages alone are provided. Commercially available targeting software packagescan fuse CT and MRI images, but to our knowledge there are no studies to sug-gest that such image fusion techniques improve targeting accuracy.

2.3.2 Physiological Targeting: Recording Techniques

The four most commonly employed techniques for physiologic localizationduring movement disorder surgery are: (1) impedance measurements; (2)macroelectrode recordings and stimulation; (3) semimicroelectrode recording(and/or stimulation); and (4) microelectrode recording (with or without stim-ulation). Evoked potentials have also been employed at times [29–33], but atpresent these are primarily used as an adjunct to stimulation during thalamicinterventions.



2.3.2.1 Impedance Techniques

Changes in electrical impedance can accurately demarcate the boundaries ofneural structures and may therefore be used to define the borders of a surgicaltarget [27, 28]. Impedance measurements can be performed with monopolarelectrodes that are referenced to the scalp [57, 81] or with concentric bipolarelectrodes employing the outer ring as the reference [56, 57, 152]. Employing atest frequency of 1 KHz, impedances of 400 Ω or greater are recorded in the deepgrey matter while white matter can be greater or less depending upon orientation.

The major advantages of this technique are the ease with which it is per-formed and the fact that the same electrode can be used during both the local-ization and the lesioning phases of an ablative procedure. The major disadvantageis the relative crudeness of the physiological information provided. Moreover,impedance measures may not adequately distinguish borders between adjacentnuclei and work best when there are clear grey matter–white matter boundariesto be defined. Therefore, impedance recordings primarily are used for the local-ization of large white matter bundles and nuclear groups [41, 152]. We performimpedance measurements during ablative procedures only after the final targetis selected via microelectrode recording (see following text), and simply toensure that the lesioning electrode has not strayed from its desired trajectoryand is located within grey matter.

2.3.2.2 Macroelectrode Recording

Macroelectrode (ME) recording, defined as any low-impedance (1–100 kΩ)recording that generates either multiunit potentials or neural background noise,provides somewhat more detailed physiologic information as compared to imped-ance measurements [20, 21, 41, 153]. The electrode tip may be as small as 50 µmand may be configured in a bipolar concentric fashion with an intertip distanceof 200–300 µm, or as a single active tip referenced to the cortical surface via theinsertion cannula or to the scalp via a surface electrode.

The main advantage of ME recording is the ease and speed with which dataare collected as compared to microelectrode techniques. The obvious disad-vantage is that EEG-like field potentials lack the discrimination necessary tocharacterize single-unit firing features within the surgical target (Fig. 16.3).Consequently, physiologic detail regarding the surgical target is lacking.

2.3.2.3 Semi-Microelectrode Technique

Electrodes that have small tip diameters (<50 µm) and impedances of100–500 kΩ are referred to as semi-microelectrodes. These electrodes providemore detailed information than do macroelectrodes, but they still do not yield



single-unit recordings. Semi-microelectrodes detect the responses of a few cells(∼10−100) (Fig. 16.4) localized to a small area around the recording tip (∼10−100 µm). These so-called field potentials are more refined than the EEG-likerecordings provided by macroelectrodes but lack the detail provided by micro-electrode techniques.

FIGURE 16.3 This is a poor semi-microelectrode recording from a substantia nigra pars reticulatacell. Note the multiple amplitude activity and the depth of EEG quality. This cell was recorded froman electrode that had an impedance of around 50 kΩ. The diameter of the electrode was around50 µm (5 s epoch).

FIGURE 16.4 Three semi-microelectrode recordings in which single units can be distinguished.What differentiates these from pure microelectrode recordings is the fact that they contain morethan one clearly distinguishable unit (5 s epoch).



2.3.2.4 Microelectrode Techniques

Microelectrodes provide the most detailed picture of the neural elementsencountered during movement disorder surgery [20, 34, 38, 53, 71, 73, 74, 102,111, 154–159]. Microelectrode tips have diameters of 1–40 µm and impedancesof ∼1 MΩ. By recording individual neuronal activity (Fig. 16.5), microelectrodesprovide real-time information concerning the physiological characteristics of therecorded neuron and thereby the nucleus within which the cell is located.

The major drawback to microelectrode recordings is the time and expertiserequired to perform the technique well. The sophisticated electronics equip-ment is expensive and must be maintained expertly. Thus the investment inmachinery and personnel can be prohibitive to some centers. It is sometimesdifficult to acquire a useful signal because of electrical noise in the operatingroom, and even in the best circumstances, recording tracts may take 20–40 minto complete. Finally, interpreting single-cell recordings is a skill that is masteredonly with experience and patience. It is our experience, however, that, oncemastered, microelectrode recording can be performed efficiently and yieldsinvaluable data concerning electrode position. For example, Alterman et al.demonstrated that in 12% of 132 consecutive pallidotomies, final lesion place-ment, as guided by microelectrode recording, was more than 4 mm removedfrom the site that was originally selected by the surgeon based on stereotacticMRI [68]. This distance is considered significant, since it is equivalent to thediameter of the typical pallidotomy lesion.

FIGURE 16.5 A set of microelectrode recordings. Note that only a single unit is being recorded.Each spike has relatively the same amplitude and shape (5 s epoch).



3 OPERATING ROOM ENVIRONMENT AND BASIC EQUIPMENT

3.1 OPERATING ROOM

3.1.1 Electrical Noise (recording only)

It is difficult to record low-amplitude neural signals reliably in the electricallyharsh operating room environment, which can affect even more robust, easilyrecorded signals, such as the EKG. Anesthesia equipment, electric cautery,lighting, radios, telemetry equipment, and countless other electronic devicescan all negatively impact recording quality. While the surgical team can con-trol the use of these devices within their own operating room, external electri-cal influences, such as ongoing construction, poor wiring, and the use of largepieces of equipment in adjacent operating rooms, may also erode recordings. Inorder to control for these external influences fully, movement disorder surgeryprocedures ideally should be performed in an electrically shielded operatingroom. Of course, few facilities possess such an expensive facility, so we makethe following recommendations:

1. Minimize any stray electrical switching noises. Typically, this type of noisederives from two sources: lighting fixtures that are equipped with dimmersand poorly shielded computer equipment. In our experience, a properlygrounded recording head stage can be operated with minimal switchinginterference when the dimmers are set either all the way on or all the way off.Fluorescent lighting may also interfere with the recording equipment, but such60-Hz signals are attenuated easily with a notch filter. Computer monitorsshould be fitted with static screen covers that can be grounded. If the monitoris part of the recording system, it can be grounded to the common systemground. Otherwise, it should be grounded to the operating room groundingsystem.

2. Employ battery-powered anesthesia and monitoring equipment. Alternatively,position anesthesia equipment in such a way as to reduce electrical interference.Turn down audible indicators. One can reduce cross-talk by keeping monitoringand neural recording cables on opposite sides of the patient. Newer anesthesiasystems are equipped with cathode ray tube (CRT), liquid crystal display (LCD),and/or plasma displays, the electromagnetic (EM) leakage from which can bebothersome. If the interference from such monitors becomes overpowering, asimple aluminum foil shield can be placed between the monitor and the re-cording stage and connected to the system ground.

3. Turn off and unplug all electrical equipment that is not in use duringrecording. Electric cautery, electrically controlled operating tables, and patient



warmers generate very powerful electromagnetic radiation. Fortunately, thesedevices are not necessary during recording and can be unplugged.

4. Employ isolated power supplies for the recording equipment. Electrical equi-pment used in adjacent operating rooms may interfere with recording due topoor operating room wiring schemes. Employing isolated power supplies andgrounded EM shields can minimize this interference.

Proper planning will help minimize most sources of noise, but noise willoccur despite the most prudent planning. It is important that both the surgeonand the neurophysiologist are prepared for these occasional frustrations. Thepatient should also be informed of the possibility of delays during the surgeryshould electrical noise be encountered. Taking the aforementioned preventivesteps minimizes the risk of encountering noise and provides a framework fromwhich one can troubleshoot noise problems when they occur.

3.1.2 Electrical Noise (internal system influences)

Sources of electrical noise from within the recording system include: (1) themicroelectrode transducer, which detects the neural activity; (2) the preamplifier,which is located close to the recording structure; (3) the amplifier; (4) signalconditioners; (5) the visual display; and (6) auditory processors (Fig. 16.6).However, electrical noise primarily enters the system proximal to the first stageof the preamplifier.

The amplitude of the recorded signals is small (range: 100 µV to 100 mV) sothat failure of any real-time component can severely compromise the integrityof the signal and, in turn, the accuracy of the mapping. Poorly designed equip-ment is the most common cause of intrasystem noise; poor system maintenanceis second. Connectors must be cleaned or replaced regularly to combat oxida-tion, particularly in high-humidity environments. Cables must also be inspectedregularly and replaced when worn.

3.2 RECORDING ELECTRODES

Lenz [36, 37] has previously described the construction of recording micro-electrodes, and Geddes [160] provides a useful description of electrode proper-ties. Microelectrode tips may be composed of a number of materials, includingstainless steel and tungsten, but the authors prefer the platinum-iridiumetched tip, which is glass coated. The tip diameter ranges from 1 to 40 µm andis beveled to a maximum diameter of 350–400 µm. The tip is coated with a thin



layer of glass to make the maximum diameter between 400 and 450 µm. Theelectrode tip is connected to a stainless steel wire (diameter: 500 µm) and aglass soldered bead. Alternatively, Epoxylite (The Epoxylite Corporation, St.Louis, MO) is used to seal the junction. An outer insulating sheath is placedover the stainless steel wire, making the total shaft diameter 600–700 µm. Anelectrode (including the tip) is typically around 300 mm in length. The last15–20 mm of insulation is removed in order to connect the electrode to theamplifier.

The electrodes exhibit a low-frequency roll-off below 1000 Hz (Fig. 16.7).The resulting reduction in transmitted power (frequency range: 100–2000 Hz)can be as much as 17.9 dB [161]. Even though cellular firing rates range from5 to 500 Hz, it is the high-frequency components that are most important forauditory discrimination. The microelectrodes exhibit adequate response char-acteristics in these higher frequencies.

Semi-microelectrodes are usually made of either stainless steel or tungstenwith tip diameters of less than 50 µm; however, tip impedance and geometryimpact recording discrimination (i.e., field potentials vs. single unit recordings)more than tip diameter [160]. Semi-microelectrodes are technically easier to

FIGURE 16.6 A representation of the signal flow through the intraoperative recording system.The microelectrode (or transducer) converts the cellular chemical potentials to a pure electricalsignal that is then passed though the amplification system. From there the data pass through a dig-itizer or audio processing system. The data are then displayed on a computer, amplified and playedthrough audio speakers, and stored for off-line analysis.



produce than microelectrodes because they can be made from existing fine wire,while microelectrode tips must be electrolytically etched.

3.3 AMPLIFICATION

The preamplifier is the first active component of the recording system. Eitherreferential or differential amplification techniques are employed to measurevoltage variations at both the active and referential inputs. Referential ampli-fiers reference the active input to a second input that is either located far fromthe active input and/or has a larger surface area than the active input. The vari-ations measured by the active input are independent of the relatively inactivereference input, permitting discrimination of the true signal. In reality, largeamplitude signals in the reference electrode may conceal smaller voltage vari-ations at the active electrode, masking signal. This possibility should be keptin mind if extensive noise is observed on the recording display. Another dis-advantage of referential recording is the possibility of amplifying noise that ismistakenly interpreted as signal. Differential amplification is superior in thisregard.

FIGURE 16.7 The gain versus frequency of the recording system. The recording system acts as ahigh-pass filter. Below 1000 Hz there is a reduction in the system’s gain. This reduction is accept-able because most of the spike energy is contained in the higher frequencies of the spike. Reprintedfrom [161].



Differential amplifiers use two active inputs and electrically subtract signalsthat are common to both. The transmission cables of both inputs run to theamplifier side by side. The amplifier receives two of the same input signal, butone is 180° out of phase from the other (i.e., one is positive while the other isnegative). The two active signals are then subtracted. Noise that is externallyinduced on the transmission cable is subtracted out since the same noise is theo-retically induced in both the transmission and reference cables. Differences inthe signals are also accentuated (SA1 + N − (−SA1 + N) = 2 SA1). The common-mode-rejection-ratio (CMRR) defines the ability of a differential amplifier toexclude common input noise. The larger this number, the greater is the reduc-tion of the induced cable noise.

We employ a differential amplifier (Model MDA4I, Atlantic Research Sys-tems, Inc., Dothan, AL) for intraoperative single-unit recording. The groundand the active input are interconnected on a large ground plane to minimizevoltage variations, which are typically close to zero. The ground plane includesthe head stage, the cerebral cortex, and the base of the isolated amplifier. Iso-lation is important for safety. These amplifiers must have a very high inputimpedance (∼200 MΩ) to enhance signal transfer from the high-impedanceelectrode (∼1 MΩ). Considering the electrode and amplifier as a voltagedivider, we see that the voltage at the amplifier is determined by the equation:

As the amplifier input impedance approaches the electrode impedance, signaltransfer decreases. The amplifier output impedance is 10 Ω. The amplifier con-sists of two sections: the preamplifier and a built-in impedance test circuit.

The preamplifier attaches to the head stage and serves not only as the first stageof the amplification section but also as a switchbox that is used to switch betweenrecording, stimulation, and impedance testing modes. Since the preamplifier isisolated from the main amplifier by an optical connection, the preamplifier ispowered from two 9-V batteries that are located in the main amplifier. Amplifi-cation control is possible via the main amplifier. The gain of the entire amplifica-tion system varies from 100 to 10,000 times with a CMRR of 80 dB at 1000 Hz.The noise floor level of the system is 5 µV when the inputs are shorted. The maxi-mum input to the amplifier is ±15 V, while the maximum linear output is 20 Vp-p.The amplifier has built-in high- and low-pass variable single-pole filters (range:1–500 Hz and 1–10 kHz, respectively).

The second component of the amplifier is a built-in impedance test circuit.This circuit passes a 30-nA (max.) current through the electrode to groundand has a range of 10 kΩ to 5 MΩ. Our standard settings are as follows: gain:approximately 4000 times; high pass filter: 100 Hz; low pass filter: 10 kHz.

VV

VAMPIN

IN=+

=( )

.200

200 10 995



3.4 STIMULATION

A number of stimulation techniques may also be performed during movement dis-order surgery. Stimulation may be delivered via macro- or microelectrodes andmay be used either to assess proximity to structures one wishes to avoid (e.g.,internal capsule, optic tract) or to assess the potential clinical effects of chronicstimulation. Many microelectrode recording systems allow the surgical team toswitch between recording and stimulation modes. This permits direct comparisonof recording and stimulation data; however, stimulation leads to a more rapiddegradation of the microelectrode, so a new electrode may be required for eachrecording tract. Moreover, the volume of tissue that can be affected with micro-electrode stimulation is so small that gross clinical changes are rarely observedwith this technique, in our experience. We therefore prefer to stimulate withmacroelectrodes, employing either the Radionics (Burlington, MA) stimulator andlesion generator prior to performing a neuroablation, or the DBS lead itself whenperforming a DBS procedure. Single- and dual-channel “screener boxes” (Fig. 16.8)are commercially available for this purpose (Models 3625 [single lead] and 3628[dual lead]; Medtronics Inc., Minneapolis, MN).

FIGURE 16.8 The Medtronic’s screener boxes. The unit on the left is a dual channel stimulatorand allows for testing two leads simultaneously. These devices are used in the operating room totest the location of the DBS electrode before final implantation. The screener boxes can also be usedwith the lead externalized while the patient is in the hospital. This gives the movement disorderteam time to test parameters without permanently implanting the whole system.



During stimulation, a train of impulses is passed through the region of inter-est and the clinical effects are noted. The stimulus can be delivered in either amono- or biphasic fashion. A monophasic stimulus varies from the reference bythe signal amplitude and then returns to the reference. The rate of change canbe edge, ramp, or sinusoidal in nature. A biphasic stimulus varies from the ref-erence in both the positive and negative directions. Typically, the amplitude ofthe change is the same in both directions, but this is not always the case. TheMedtronics, Inc. implantable neural stimulators generate a biphasic pulse witha positive component that is less intense than the negative component.

Stimulation may also be mono- or bipolar in nature. Monopolar stimulationis generated at the active tip and is referenced to some distant point. With bipo-lar stimulation, the active and reference electrodes are in close proximity so thatcurrent flows within a tightly defined space. The concentric ring electrode is acommonly employed bipolar stimulation configuration where the inner tip isthe active electrode and the outer ring is the reference electrode. Chronicallyimplanted DBS leads are equipped with four contacts arranged in series, allow-ing for either mono- or bipolar stimulation employing any one or combinationof contacts. In order to deliver a monopolar stimulus, the active contact(s)is(are) referenced to the pulse generator case. Bipolar stimuli are conductedbetween any combination of contacts. Table 16.1 demonstrates some of theimportant specifications for stimulators.

TABLE 16.1 Stimulator Specifications

Feature First type Second type

Output Polarity Bi-Phasic – Deviations in both the Mono-Phasic – Single deviationpositive and negative directions from the reference pointfrom the reference point

Constant Measure Constant Current – The current Constant Voltage – The voltage ofof the device is set by the user, the device is set by the user,and the stimulator adjusts the and the stimulator adjusts the voltage to compensate for current to compensate for theimpedance deviations impedance deviations.

Pulse Width The width of each pulse

Frequency The number of pulses per second

Train Length The time that the stimulator presents a set of pulses

Amplitude The strength of the stimulus

Wave Shape The type of waveform. Most stimulators used for these procedures generate square pulses.



4 TECHNIQUE FOR MOVEMENT DISORDER SURGERY

A detailed account of our surgical technique is beyond the scope of this book.Instead, we will provide a brief overview of our general technique for perform-ing movement disorder surgery and detail the physiological localization meth-ods we employ for each surgical target. The interested reader is directed to amore detailed description of our preferred technique [131].

4.1 GENERAL STEREOTACTIC TECHNIQUE

The stereotactic headframe is applied on the morning of surgery with localanesthetic (Fig. 16.9). Care is taken to center the head within the frame and toalign the base ring of the frame with the orbitomeatal line, which approximatesthe orientation of the AC-PC line. In this way, axial images obtained perpen-dicular to the axis of the frame will run parallel to the AC-PC plane. The patientis transferred to radiology, where a stereotactic MRI is performed. We employ

FIGURE 16.9 The stereotactic frame with the MRI localizer box. The plastic box is used to addcoordinate points the surgeon can use to locate objects in the frame’s three-dimensional space.



axial fast spin-echo inversion recovery MRI to localize the commissures anddetermine their stereotactic coordinates. We then derive the coordinates of themidcommissural point (MCP) by averaging the coordinates of the commis-sures and calculate the coordinates of our surgical target based on its rela-tionship to the commissures and/or the MCP. The calculations employed for themost commonly targeted sites are given in Table 16.2.

The patient is returned to the operating room (Fig. 16.10 shows the roomlayout that we employ at our center) and is positioned supine on the operatingtable, which is configured as a reclining chair for the patient’s comfort. The target

TABLE 16.2 Initial Target Coordinates

Medial lateral Anterior-posterior Ventral-dorsalTarget coordinate coordinate coordinate

GPi 20–23 mm from midline 2–3 mm anterior to MCP 6 mm ventral to AC-PC

VIM 13–15 mm from midline 5–6 mm anterior to PC 0 mm from AC-PC

STN 12 mm from midline 2 mm posterior to MCP 6 mm ventral to AC-PC

FIGURE 16.10 Layout of our operating room. This particular setup has been found to minimizenoise.



coordinates are set on the frame, bringing the presumptive target to the centerof the operating arc. The operation is performed through a 14-mm burr holethat is positioned approximately 1 cm anterior to the coronal suture and 2–3 cmlateral of the midline. The dura mater is opened and microelectrode recordingis begun.

The microdrive adapter and the X-Y adjustment stage are mounted onto theoperating arc. The microelectrode is back-loaded into the microdrive andzeroed to the guide tube. The electrode is withdrawn into the cannula (∼5 mm)for safe insertion. An insertion cannula is advanced through the frontal lobe toa point that is 20 mm anterosuperior to the presumptive target. The guide tubecontaining the recording electrode is inserted into the insertion cannula and themicrodrive apparatus is mounted to the X-Y adjustment stage. At this point theguide tube, to the end of which the electrode tip position is zeroed, is flush withthe end of the insertion cannula. Thus recording begins 20 mm anterosuperiorto the presumptive target.

The electrode is driven 3.0 mm into the brain and the impedance of theelectrode–tissue system is measured. In our experience, impedances of 700 KΩto 1.2 MΩ provide the best single-unit recordings. Even with conditioning ofthe electrode and stimulation testing, these starting impedances allow for suf-ficient current passage without degradation of the recording electrode surface.If there is a large impedance drop following electrode conditioning, the elec-trode is deemed unacceptable and is replaced. We correct any noise problemsat this time and then proceed to data acquisition.

At the conclusion of each recording trajectory, the collected data aremapped onto scaled sagittal sections derived from the Schaltenbrand-Wahrenstereotactic atlas [164], and a determination is made as to tract location andorientation employing a “best fit” model (see data organization section). Whenthe data suggest that our targeting is correct, we proceed either to test stimu-lation and ablation or DBS lead insertion. Detailed discussions of microelec-trode recording and macroelectrode stimulation, as we employ them for eachof the three primary movement disorder targets, are described in the follow-ing sections.

4.1.1 GPi Procedures1

Posteroventral pallidotomy and GPi deep brain stimulation are reported toimprove tremor, rigidity, and LID in patients with medically refractory, mod-erately advanced PD. Though the published experience is limited, preliminary

1 To hear single-unit examples: (1) go to Chapter 16 from the main menu; (2) select the targetof interest (GPi, VIM, STN) with the left mouse button; (3) select the single-unit example with theleft mouse button.



results suggest that GPi stimulation yields results that are similar to pallido-tomy, with the added benefit that bilateral stimulation can be performed moresafely than bilateral pallidotomy.

Profound improvements have also been reported in patients with DYT1-associated primary dystonia in whom GPi stimulation was performed. Theauthors have performed seven of these procedures, noting dramatic improvementsin tone, posture, and overall motor function. Of course, further study is requiredbefore the full benefit of this surgery in primary and secondary dystonias is known.

Successful pallidal interventions require targeting of the sensorimotor regionof GPi, which lies posterior and ventral in the nucleus. When recording in thisregion, three key nuclear structures must be recognized: the striatum, the GPe,and the GPi (Fig. 16.11) (see also color plate). Our typical trajectory passes at a60–70° angle above the horizontal of the AC-PC line, and at a medial-lateral angleof 90° (i.e., true vertical). By employing this purely parasagittal trajectory, we canmore readily fit the operative recording data to the parasagittal sections providedin human stereotactic atlases.

The first cells encountered during recording are in the corpus striatum(caudate and putamen; colored blue in Fig. 16.11). They exhibit characteristic

FIGURE 16.11 Sagittal slice through the globus pallidus, taken 20.0 mm from the midline. Thecolor shading is referenced in the text. Reprinted from [164] (see also color plate).



low-amplitude action potentials, which sound like corn popping (Fig. 16.12A,CD-GPi sound 1). Cellular activity in this area is extremely scanty, and the back-ground is quiet. The electrode may also traverse some quiet regions that representsmall fingerlike projections of the internal capsule into the striatum.

Either the detection of a border cell or an increase in background activitymarks entry into the GPe, the next structure to be encountered. Border cells(Fig. 16.12B, CD-GPi sound 2) exhibit very low frequencies (between 2 and20 Hz) that are highly periodic and high-amplitude spikes with moderate towide firing times. Though rare in this region, border cells greatly facilitate local-ization of the boundaries within the globus pallidus.

Two major cell types are found within the GPe: pausers (Fig. 16.12C, CD-GPi sound 3) and bursters (Fig. 16.12D, CD-GPi sound 4). Pauser cells firearrhythmically at a frequency of 30–80 Hz. They exhibit moderate to highamplitude discharges, a shorter time period, and lower amplitude than the

FIGURE 16.12 Representative tracings of cellular activity that may be encountered during a GPirecording trajectory. Each tracing is 5 s in length, except for trace GG, which is 1 s in length. (A)(Sound 1) Low frequency, and sparse single spikes of the striatum. (B) (Sound 2) Boarder cell. (C)(Sound 3) GPe pauser cell. (D) (Sound 4) GPe burster cell. (E) (Sound 5) The X-cell represents acell that is dying. (F) (Sound 6) A GPi tremor cell. (G and GG) (Sound 7) A high-frequency cellfrom GPi. (H) (Sound 8) The entry of the microelectrode into the optic tract. The point at whichthe amplitude starts to increase represents the optic tract entry.



border cells. They are distinguishable by their staccato-type, asynchronouspauses. An extremely small number of pauser cells (<5%) may demonstratesomatotopically organized kinesthetic responses.

As their name implies, burster cells are distinguished by short bursts ofhigh-frequency discharges, achieving rates as high as 500 Hz. Amplitudesvary but are usually less than the amplitudes of the pauser cells. It is impor-tant to differentiate bursters from what we refer to as X-cells (Fig. 16.12E,CD-GPi sound 5). X-cells exhibit high-frequency discharges (near 500 Hz)with a time-related (<30 s) decrease in amplitude, representing death of thecell.

We may encounter anywhere from 4 to 8 mm of GPe during one recordingtract. Border cells are again encountered at the inferior border of GPe and are moreplentiful in this region. A quiet laminar area (Fig. 16.11) is encountered upon exitfrom the GPe, marked by a steep dropoff in background activity.

Border cells are again encountered upon entry into the GPi, and again, twoclasses of neurons predominate within the nucleus: tremor-related cells andhigh-frequency cells. Tremor cells (Fig. 16.12F, CD-GPi sound 6) fire rhyth-mically in direct relation to the patient’s tremor. Single-unit recordings show afrequency modulation pattern, while semi-microelectrode recordings show afrequency and amplitude modulation pattern. The firing rate of these cells isbetween 80 and 200 Hz.

High-frequency cells (Fig. 16.12G, CD-GPi sound 7) are characterized byfiring rates that are similar to the tremor cells (80–100 Hz), but are much morestable, exhibiting consistent amplitude and frequency. Many of these cellsrespond to active or passive range of motion of a specific joint or extremity.Guridi et al. have physiologically defined a somatotopic organization of thekinesthetic cells in the GPi, with the face and arm region located ventrolaterallyand the leg dorsomedially [69]. Taha et al. found a slightly different arrange-ment, with the leg sandwiched centrally between the arm in both the rostral andcaudal areas [74]. Vitek et al. have found the leg to be medial and dorsal withrespect to the arm, and the face more ventral [16]. The GPi is subdivided intoexternal and internal segments, labeled GPie (external GPi) and GPii (internalGPi), respectively. Both regions exhibit similar cellular recording patterns, butGPie may exhibit less cellularity than GPii. Total GPi recordings normally spanfrom 5 to 12 mm. A steep dropoff in background activity denotes exit from theGPi inferiorly.

Three important white matter structures border the GPi and may beencountered during recording. The ansa lenticularis (AL), which emerges fromthe base of the GPi, carries motor-related efferents from the GPi to the ven-trolateral thalamus, merging with its sister pathway, the lenticular fasciculusat the H field of Forel. The AL is an electrically quiet region, although rare cellsof relatively low amplitudes and firing frequencies can be recorded. It has been



proposed that lesioning within the AL generates the best results from pos-teroventral pallidotomy.

The optic tract (OT) lies directly inferior to the AL (Fig. 16.11, CD-GPisound 8), accounting for the high rate of visual field complications reported inthe early modern pallidotomy literature [17, 60]. With quality recordings, it ispossible to hear the microelectrode tip enter the OT, the sound of which isreminiscent of a waterfall. Upon hearing this background change, one may con-firm entry into the optic tract by turning off the ambient lights and shining aflashlight in the patient’s eyes. This will increase the recorded signal if the elec-trode is within the OT. Finally, one may encounter the internal capsule. Back-ground recordings within the capsule are similar to those of the OT. Movementof the mouth or contralateral hemibody will generate a swooshing sound that iscorrelated to the movement. Obviously, one wishes to avoid the posterior cap-sule when making a lesion or placing a DBS lead, since a hemiparesis or hemi-plegia may result.

Macroelectrode stimulation is performed prior to lesioning to ensure that theelectrode is a safe distance from the internal capsule and the OT. We conducttest stimulation with the Radionics 1.1-mm by 3-mm exposed-tip stimulatingand lesioning electrode (Radionics, Burlington, MA), employing a stimulationfrequency of 60 Hz and a pulse width of 0.2 ms at 0–10 V. Stimulation of con-tralateral muscular contractions at less than 2.5 V suggests that the lesioningelectrode is too close to the internal capsule and should be adjusted laterally.Induction of phosphenes at less than 2.0 V suggests that the electrode is too closeto the OT and should be withdrawn slightly. Test stimulation should be per-formed at 2- to 3-mm intervals beginning 6–8 mm above the base of GPi asdefined by MER. Decreasing voltage trends in the induction of muscular con-tractions and/or phosphenes should be monitored. If stimulation is begun infe-riorly, one risks creating a tract through which current may leak, resulting inpersistently low thresholds for the stimulation of phosphenes that will cause thelesioning probe to be withdrawn too far. A suboptimal lesion may result. Detailsof this technique have been published previously [76]. Employing this tech-nique, one of the authors (RLA) has performed more than 110 pallidotomieswithout inducing visual field abnormalities or hemiparesis.

If stimulation indicates that the targeted region is a safe distance from theinternal capsule and OT, the therapeutic lesion is placed. Ablation begins at thebase of the GPi and progresses upward in 2-mm increments, creating a cylin-drical lesion that encompasses the span of GPi as defined by MER. A test lesionis initially performed at 40°C for 40 s, after which the patient’s visual fields andbasic motor function are checked. If there are no adverse visual field or motorchanges, a permanent lesion is performed at 80°C for 60 s. Ideally, lesionsshould not encroach upon the GPe, because the working model of basal gangliaphysiology suggests that GPe lesioning may worsen parkinsonism.



Excellent pallidotomy results also have been reported without the use ofmicroelectrode recording and with the performance of ablations of varyingsize ranges. To date, no correlation between lesion size and surgical outcomehas been made.

4.1.2 VIM Procedures

Therapeutic neuroablation or chronic high-frequency electrical stimulationwithin the ventral intermediate nucleus of the thalamus (VIM; Fig. 16.13) (seealso color plate) suppresses parkinsonian and essential tremor without adverselyaffecting voluntary motor activity to a significant degree (thalamotomy may beassociated with some loss of fine dexterity). Thalamic interventions are extremelygratifying to perform because of the immediacy of the results and the well-definedphysiology of the motor and sensory thalamic nuclei [41].

When targeting VIM, our standard angles of approach are 60–70° relative tothe AC-PC line, and 5–10° lateral of the true vertical. Pure parasagittal trajec-tories cannot be employed as they are in globus pallidus procedures due to themedial location of the target and a desire to avoid the ipsilateral lateral ventricle.

FIGURE 16.13 Sagittal slice through the thalamus taken 14.5 mm from the midline. The colorshading is referenced in the text. Reprinted from [164] (see also color plate).



Transit through the ventricle may increase the risk of hemorrhage and typicallyleads to more rapid loss of cerebral spinal fluid (CSF) with resulting brain shiftand loss of targeting accuracy.

Recording begins in the dorsal thalamus, where cells characterized by lowamplitudes and sparse firing patterns are encountered. Bursts of activity andsmall-amplitude single spikes (Fig. 16.14A, CD-VIM sound 9) are typical find-ings in this region. Upon exiting the dorsal thalamus, the electrode enters theVL nucleus, which is composed of nucleus ventralis oralis anterior (VOA), ven-tralis oralis posterior (VOP), and VIM. The dorsal third of the VL nucleus issparsely populated such that cellular recordings in this area are similar to thoseof the dorsal thalamus. As the electrode passes ventrally within the VL complex,cellular density increases and cells with firing rates of 40–50 Hz (Fig. 16.14B,CD-VIM sound 10) are encountered. Kinesthetic cells with discrete somato-topic representation are routinely encountered. This organization permits anassessment of the mediolateral position of the electrode. The homunculus of the

FIGURE 16.14 Representative tracings of cellular activity that may be encountered during a VIMrecording trajectory. Each tracing is 5 s in length. (A) (Sound 9) Sparse dorsal thalamic cells. (B)(Sound 10) Nontremor VIM cell. (C) (Sound 11) VIM tremor cell. (D) (Sound 12) Nonsensory VCcell. (E) (Sound 13) Finger VC sensory cell. Note the increase in firing rate as a light bristle paintbrush is dabbed against the finger.



ventrocaudal (Vc) and VIM nuclei are virtually identical: representation of thecontralateral face and mouth lies 9–11 mm lateral of midline, the arm is repre-sented lateral to this at 13–15 mm lateral of midline, and the leg is more lateralstill, adjacent to the internal capsule. Thus, if one encounters a cell that respondsto passive movement of the ankle, one knows that one has targeted too laterallyto treat an upper-extremity tremor and should adjust the mediolateral positionaccordingly.

In addition to kinesthetic neurons, one will routinely encounter “tremor”cells (Fig. 16.14C, CD-VIM sound 11) within the VIM of tremor patients. Thesecells exhibit a rhythmic firing pattern that can be synchronized to EMG record-ings of the patient’s tremor [37]. Lenz et al. demonstrated that these cells areconcentrated within VIM, 2–4 mm above the AC-PC plane, a site that is empir-ically known to yield consistent tremor control [162].

The recording electrode may exit VIM inferiorly, passing into the zonaincerta (ZI) with a resulting decrease in background signal, or it will enter Vc,the primary sensory relay nucleus of the thalamus. Entry into Vc is markedby a change in the background signal. Cells in this region are densely packed,exhibit high amplitudes, and respond to sensory phenomena (e.g., lighttouch) with a discreet somatotopic organization, which mirrors that of VIMand may also be used to assess target laterality (Fig. 16.14D, CD-VIM sound12). A typical cell, which responds to lightly brushing the patient’s finger, isfeatured in Fig. 16.14E (CD-VIM sound 13). Note the increase in firing rateas a light bristle paintbrush is dabbed against the finger. The bars representthe times that the brush is being dabbed against the finger. If Vc is encoun-tered early in the recording trajectory, the electrode may be targeted posteri-orly and should be adjusted anteriorly. The nucleus ventrocaudalis parvo-cellularis (VCpc) rests inferiorly to Vc. Recordings within this nucleus aresimilar to those of Vc; however, stimulation in this location may yield painfulor temperature-related sensations. Single-unit recordings in this area willrespond to both painful and temperature-related stimuli applied within thecell’s receptive field.

Stimulation within the thalamus for the purposes of localizing therapeu-tic lesions may be performed with constant-voltage or constant-currentdevices, and with micro- or macroelectrodes. When stimulating with con-stant current, we employ 60 µs and 1 ms pulse widths at a frequency of 180 Hz.Regardless of technique, the reference is a cautery ground pad that is placedon the back of the thigh ipsilateral to the side of the stimulation. We considera motor stimulation threshold of 1 mA or 3 V safe for placing a thalamotomylesion.2

2 Note that the threshold values described in this chapter are specific to the stimulators, stim-ulator parameters, and electrode geometries that we employ.



When performing VIM DBS, we use the lead itself to perform test stimula-tion. In such cases bipolar stimulation is performed so that a reference pad isunnecessary. In our experience, a properly positioned DBS lead results intremor arrest at <3 V (pulse width: 60 µs; frequency: 180 Hz). Transient pares-thesias are common with a properly positioned electrode; however, persistentparesthesias, which are induced at low voltages, indicate that the electrode is posi-tioned posteriorly, near or within Vc. Failure to suppress tremor or induce pares-thesias, even at 5 V, suggests that the electrode is positioned anteriorly withinVOA. Muscular contractions (typically of the contralateral face and/or hand) sug-gest that the lead is positioned too laterally and stimulation is affecting the inter-nal capsule.

It has been our experience that microelectrode stimulation may not suppresstremor at sites where macroelectrode stimulation is effective.

4.1.3 STN Procedures

Bilateral STN DBS appears to be the most effective treatment for PD since lev-odopa, which was introduced more than a generation ago. Subthalamic DBSimproves all of the cardinal features of PD, dampens the severity of “on–off”fluctuations, alleviates freezing spells, and dramatically reduces medicationrequirements.

The STN is approached at an angle of 70° relative to the AC-PC line and10–15° lateral of the true vertical. Microelectrode recording begins in the ante-rior thalamus and passes sequentially through the ZI, Forel’s field H2, the STN,and the substantia nigra pars reticulata (SNr) (Fig. 16.15) (see also colorplate).

In the thalamus, one encounters cells that fire with low amplitude and fre-quency. Two patterns of activity may be identified: (1) bursts of activity(Fig. 16.16A, CD-STN sound 1) and; (2) irregular, low-frequency (1–30 Hz)activity (see Chapter 16, CD-video segment 1) (Fig. 16.16B, CD-STN sound 2).The density of cellular activity varies in this region. For example, we haveobserved that VOA is more cellular than the reticular thalamus.

The border between the thalamus and ZI (Fig. 16.16C, CD-STN sound 3)may be very distinct, but not in all cases. Developmentally, the ZI is a continu-ation of the reticular nucleus of the thalamus, and the transition from one to theother may not be clear. The ZI can be differentiated electrophysiologically fromthe thalamus in two ways. First, cellular activity is more muffled or “muddy” inthe ZI. By this we mean that the cellular firing rates slow and become a little moreasynchronous, and the amplitudes decrease in intensity. These changes aresubtle and can be missed by inexperienced observers. The second indicationof transition from thalamus to ZI is a change in the background recordings.



Whereas the background of the thalamus proper is somewhat active, the ZIbackground is much quieter. Typically, the recording electrode will exit thethalamus 6–10 mm anterosuperior to our presumptive target and will passthrough 2.5–4.0 mm of ZI before entering H2. If more than 4 mm of relative“quiet” is encountered, a trajectory that is anterior or posterior to the STNshould be suspected.

A decrease in background activity demarcates entry into Forel’s field H2,which lies immediately superior to the STN, 10–12 mm lateral of midline.Sparse cellular activity is detected over a span of 1–2 mm. Background activityincreases as the recording electrode enters STN. Additionally, dense cellularactivity is now encountered. Two patterns of cellular activity are observedwithin STN: (1) tremor activity (Fig. 16.16D, CD-STN sound 4) similar to thatencountered in VIM or GPi; and (2) single-cell activity (Fig. 16.16E, CD-STNsound 5) with frequencies that vary from ∼25 Hz to 45 Hz. Cells in the dorsalsegments of the STN exhibit slower firing rates than those of the ventral STN(A. Beric, personal communication). Kinesthetic related activity (see Chapter 16CD-video segments 2 and 3) is often observed, but a clear somatotopy is not evi-dent. Upon exiting the STN, the microelectrode may pass through a thin quiet

FIGURE 16.15 Sagittal slice through the STN taken 12.0 mm from the midline. Reprinted from[164] (see also color plate).



zone or will pass directly into the SNr. Entry into the SNr is demarcated by sig-nificant increases both in background neural activity and in cellular firing rates(Fig. 16.16F, CD-STN sound 6), which are usually greater than 60 Hz. Up to7 mm of SNr may be encountered, depending on the anteroposterior positionof the trajectory.

We require 4–6 mm of STN, preferably with evidence of kinesthetic activity,for implantation of the DBS lead. This large a span allows for two of the fourelectrode contacts to be placed within the nucleus, leaving the other two abovethe nucleus in the ZI and H2. Additionally, this large a span of STN recordingensures that the electrodes are implanted solidly within the nucleus and notnear a border.

The primary goal of test stimulation at the STN is to check for stimulation-induced adverse events (AEs) because, aside from tremor arrest and somemodest reductions in rigidity, positive STN stimulation effects may not beobserved for hours or days. Test stimulation is performed in bipolar configuration

FIGURE 16.16 Representative tracings of cellular activity that may be encountered during a STNrecording trajectory. Each tracing is 5 s in length, except for trace FF, which is 1 s in length. (A)(Sound 14) Thalamic burster cell and single cell. (B) (Sound 15) Thalamic single cell. (C) (Sound16) ZI cellular activity. (D) (Sound 17) STN tremor cell. (E) (Sound 18) Nontremor STN cell fromthe ventral half of the STN nucleus. (F) (Sound 19) SNr cell.



with the implanted DBS lead and Medtronic’s single lead screener (model 3625,Medtronic, Minneapolis, MN). Parameters are: 60 µs, 180 Hz, 0–4 V. We do notstimulate higher than 4.0 V for fear of inducing hemiballism. Moreover, wehave yet to employ amplitudes greater than 4 V to achieve clinical benefit at thistarget. Transient paresthesias are frequently encountered with the onset of stim-ulation. Persistent paresthesias indicate stimulation of the medial lemniscalpathway, which lies posterolateral to the nucleus. Stimulation-induced con-tractions of the contralateral hemibody and/or face indicate anterolateral mis-placement of the lead. Finally, abnormal eye movements may be encounteredif the lead is positioned too medially or deep to the nucleus. The first test stim-ulation is performed using contacts 0−, 1+ up to a voltage of 4.0 V. If no signif-icant adverse effects are encountered with this focal test, we proceed to teststimulation employing all four contacts (i.e., 0−, 1−, 2+, 3+ up to a voltage of4.0 V). This test covers the full contact space of the electrodes and focuses onidentifying stimulation-induced adverse events in the ventral aspect of the stim-ulation field. This is the area where most AEs have occurred in our experience.The final stimulation is performed using contacts 0+, 1+, 2−, 3− up to a voltageof 4.0 V. This examines the dorsal aspect of the stimulation field.

4.1.4 Data Organization

The data from each microrecording tract are plotted on scaled graph paper(1.0 cm: 1.0 mm) [17, 163]. The borders of each encountered structure aremarked, and the span of each region is represented by a different color foreasy differentiation. In order to accurately account for our angle of approach,a line that is parallel to the intercommissural line is also drawn. The plottedtract is then traced onto a transparent plastic sheet. The transparency isplaced on scaled maps (10:1) derived from the Schaltenbrand-Wahren humanstereotactic atlas [164] (see Chapter 16, CD-video segment 4 for a STN pro-cedure and Fig. 16.17 (see also color plate) for a GPi procedure) in order todetermine to which map the trajectory best fits. The accuracy of the fit isdependent upon the number of trajectories, the number of structures encoun-tered along each trajectory, and finally upon how well the patient’s anatomyfits the atlas, which is derived from a single human specimen. It can be diffi-cult to find one place to which a single tract fits best, especially when per-forming pallidal or thalamic interventions. When mapping the STN, the manystructures encountered along a single trajectory make fitting it to the atlas alittle more straightforward. If there is any question about the proper fit of thedata, we perform another recording tract. Knowing the spatial relationshipbetween each tract, we can better fit all of the data to the atlas with each sub-sequent trajectory.



FIGURE 16.17 Once the recording data are transferred to 1:10 scaled graph paper, the trajecto-ries are transferred to a transparency. The angle of the trajectory relative to the AC-PC line is addedto the transparency, and the trajectory is then fitted to scaled atlas sections. This figure shows twotrajectories during a GPi lesion surgery. The green lines represent the GPe part of the trajectory,and the red lines represent the GPi part of the trajectory. By overlaying two atlas maps, a three-dimensional picture of the trajectories can be formed. Original non-scaled or enhanced tracingfrom [164] (see also color plate).



5 CONCLUSION

The fine details of these procedures vary from center to center, but theneurophysiological techniques used by each center can be divided into thefollowing categories: (1) microrecording; (2) semi-microrecording; (3) stimu-lation; and (4) evoked response testing. In the over 1,500 trajectories performedby the authors, we feel that the information gathered with microrecording isof great benefit when performing these surgeries. Microrecording has beenshown to be as safe as other stereotactic procedures [165] when done prop-erly. With these surgeries we are trying to modify the physiology of a targetstructure; therefore, microrecording gives specific physiologic data to helpdetermine the optimal placement. In most cases (43–88%, depending on thestudy [69, 114, 139]), this physiological target corresponds to the anatomictarget, but in the 12–67% of cases that is not the case. At present there is noway of knowing which of these patients will fall into either category before thesurgery.

The neurophysiologic techniques used in the operating room require trainedand skilled personnel, not only to acquire but also to interpret the data. If every-thing goes perfectly, the data are relatively easy to interpret, but when the sig-nals are not textbook cases, this interpretation needs to be done by veryexperienced personnel. Up until the mid-1990s, centers had to put their ownmicroelectrode recording systems together and build their own microelec-trodes, since there were no commercially available systems. At the present timethere now exist about 10 companies (internationally) that produce micro-recording systems, and the first FDA-approved microelectrodes were placed onthe market in 2000. The key points to get the best signals at are the microelec-trode, preamplifier, and amplifier. The main feature of reliable microelectrodesystems for neurophysiological targeting of deep brain structure is the qualityof the recorded signal. This is more important than any of the fashionable fea-tures that many manufactures offer. No software-based interpretation scheme isgoing to replace the skilled human interpreter when the recordings are difficult.As already stated, the operating room is very harsh electrically. The more welearn about the areas of interest, the faster and smoother each of these proce-dures will go.

Included with the CD at the end of the book is a short video that demon-strates the recording of an anterior thalamic cell, the kinesthetic response of theSTN to passive and active movements of the patient’s right wrist, and a singletrajectory showing the relationship of the recordings for that tract to the scaledatlas maps. The CD also includes examples of single-unit recordings from thevarious structures described in this chapter.



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(1992). A comparison between magnitude resonance imaging and computed tomography forstereotactic coordinate determination. Neurosurgery, 30, 402–407.

139. Alterman, R.L., Reiter, G.T., Shils, J., Skolnick, B., Arle, J.E., Lesutis, M., Simuni, T., Colcher,A., Stern, M., and Hurtig, H. (1999). Targeting for thalamic deep brain stimulation implanta-tion without computer guidance: Assessment of targeting accuracy. Stereotact. Funct. Neuro-surg., 72, 150–153.

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141. Starr, P.A., Vitek, J.L., DeLong, M., and Bakay, R.A.E. (1999). Magnetic resonance imaging-based stereotactic localization of the globus pallidus and subthalamic nucleus. Neurosurgery,44, 303–314.



142. Reich, C.A., Hudgins, P.A., Sheppard, S.K., Starr, P.A., and Bakay, R.A.E. (2000). A high-resolution fast spin-echo inversion-recovery for preoperative localization of the internal globuspallidus. Amer. J. Neuroradiol., 21, 928–931.

143. Zonenshayn, M., Rezai, A.R., Mogilner, A.Y., Beric, A., Sterio, D., and Kelly, P.J. (2000).Comparison of anatomic and neurophysiologic methods for subthalamic nucleus targeting.Neurosurgery, 47, 282–294.

144. Sumanaweera, T.S., Adler, J.R., Napel, S., and Glover, G.H. (1994). Characterization of spa-tial distortion in magnetic resonance imaging and its implications for stereotactic surgery.Neurosurgery, 35, 696–704.

145. Gerdes, J.S., Hitchon, P.W., Neerangun, W., and Torner, J.C. (1994). Computed tomographyversus magnetic resonance imaging in stereotactic localization. Stereotact. Funct. Neurosurg.,63, 124–129.

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148. Alterman, R.L., Shils, J.L, Tagliati, M., and Rogers, J. (2000), Relative accuracy of inversionrecovery and T2-weighted MRI for targeting the subthalamic nucleus. Presented at the XIVthEuropean Society for Stereotactic and Functional Neurosurgery, London, U.K.

149. Shils, J.L., and Alterman, R.L. (2000). Comparative accuracy of stereotactic coordinatesderived from various MRI acquisition techniques. Presented at the XIVth European Society forStereotactic and Functional Neurosurgery, London, U.K.

150. Holtzheimer, P.E., Roberts, D.W., and Darcey, T.M. (1999). Magnetic resonance imagingversus computer tomography for target localization in functional stereotactic neurosurgery.Neurosurgery, 45, 290–298.

151. Axer, H., Stegelmeyer, J., and von Keyserlingk, D.G. (1999). Comparison of tissue impedancemeasurements with nerve fiber architecture in human telencephalon: Value in identificationof intact subcortical structures. J. Neurosurg., 90, 902–909.

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153. Yoshida, M., Yanagisawa, N., Shimazu, H., Givre, A., and Narabayashi, H. (1964). Physiolog-ical identification of the thalamic nucleus. Arch. Neurol., 11, 435–443.

154. Guridi, J., and Lozano, A.M. (1997). A brief history of pallidotomy. Neurosurgery, 41,1169–1180.

155. Ohye, C., and Narabayashi, H. (1979). Physiological study of presumed ventralis intermediusneurons in the human thalamus. J. Neurosurg., 50, 290–297.

156. Hardy, J. (1966). Electrophysiological localization and identification. J. Neurosurg., 24,410–414.

157. Lozano, A., Hutchison, W., Kiss, Z., Tasker, R., Davis, K., and Dostrovsky, J. (1996). Meth-ods for microelectrode-guided posteroventral pallidotomy. J. Neurosurg., 84, 194–202.

158. Hirai, T., Miyazaki, M., Nakajima, H., Shibazaki, T., and Ohye, C. (1983). The correlationbetween tremor characteristics and the predicted volume of effective lesions in stereotaxicnucleus ventralis intermedius thalamotomy. Brain, 106, 1001–1018.

159. Gillingham, F.J. (1966). Depth recording and stimulation. J. Neurosurg., 24, 382–387.160. Geddes, L.A. (1972). “Electrodes and the measurement of bioelectric events.” Wiley-Interscience,

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161. Shils, J.L., Patterson, T., and Stecker, M.M. (2000). Electrical properties of metal microelec-trodes. Amer. J. Electrodiag. Technol., 40, 71–82.

162. Lenz, F.A., Tasker, R.R., Kwan, H.C., Schnider, S., Kwong, R., Murayama, Y., Dostrovsky, J.O.,and Murphy, J.T. (1988). Single unit analysis of the human ventral thalamic nuclear group:Correlation of thalamic “tremor cells” with the 3–6 Hz component of parkinsonian tremor. J.Neurosci., 8, 754–764.

163. Starr, P.A., Vitek, J.L., and Bakay, R.A.E. (1998). Deep brain stimulation for movement dis-orders. Neurosurg. Clin. N. Amer., 9, 381–402.

164. Schaltenbrand, G., and Wahren, W. (1977). “Atlas for stereotaxy of the human brain.”Thieme, New York.

165. Alterman, R.L., and Kelly, P.J. (1998). Pallidotomy technique and results. Neurosurg. Clin. N.Amer., 9, 337–343.


FIGURE 10.2 Rootlet of L5 sensory root being held by stimulator probes away from rest of sensory root.

FIGURE 16.1 A three-dimensional artist's rendition of the structures involved in surgery for movement disorders. The light greenish blue structure on the left is the globus pallidus (GPi and GPe). The large grey structure on the right is the thalamus, and the small dark green structure is the subthalamic nuclei (STN). The medial edge of the STN is only 6.0 m m from the midline of the brain. With the trajectories that our group uses in the operating room, we encounter around 10.0 m m of GPi, 11.0 m m of VIM, and 5.0 m m of STN. Modified from [117].

,,,,, M EDIAL

POSTERIOR

SU PER IOR / DORSALI

ANTERIOR

LATERAL ~r INFERIOR/VENTRAL

FIGURE 16.11 Sagittal slice through the globus pallidus, taken 20.0 mm from the midline. The color shading is referenced in the text. Reprinted from [164].

AL )

SUPERIOR I DORSAL

ANTERIOR

i

POSTERIOR

LATERAL ~r INFERIOR / VENTRAL

FIGURE 16.13 Sagittal slice through the thalamus taken 14.5 mm from the midline. The color shading is referenced in the text. Reprinted from [164].

DIAL SUPERIOR I DORSAL T

POSTERIOR

ANTERIOR L

LATERAL

INFERIOR I VENTRAL ~1 ~ ~ i ~

FIGURE 16.15 Sagittal slice through the STN taken 12.0 mm from the midline. Reprinted from [164].

FIGURE 16.17 Once the recording data are transferred to 1:10 scaled graph paper, the trajecto m ries are transferred to a transparency. The angle of the trajectory relative to the ACmPC line is added to the transparency, and the trajectory is then fitted to scaled atlas sections. This figure shows two trajectories during a GPi lesion surgery. The green lines represent the GPe part of the trajectory, and the red lines represent the GPi part of the trajectory. By overlaying two atlas maps, a three- dimensional picture of the trajectories can be formed. Original non-scaled or enhanced tracing from [164].

C H A P T E R 17

Anesthesia and Motor Evoked PotentialMonitoringTOD B. SLOAN

Department of Anesthesiology, University of Texas Health Science Center,San Antonio, Texas

1 Introduction2 Overview3 Effects of Specific Anesthetic Agents

3.1 Halogenated Inhalational Agents3.2 Intravenous Analgesic Agents3.3 Muscle Relaxants

4 Conclusion: Anesthetic Choice for Motor Tract Monitoring

References

ABSTRACT

Anesthesia used to conduct surgery where motor evoked potential (MEP) monitor-ing is used has marked effects on the ability to record responses. This review willfocus on both the theory and the practical issues of the effects of anesthetic agents.In theory, the type of interaction should be predictable, based on the mechanism ofaction of the drugs involved. Unfortunately, we do not have a thorough under-standing of the mechanisms of anesthesia. However, the major target of anestheticaction appears to be at the gaba amino butyric acid (GABA) and the n-methyl-d-aspartic acid (NMDA) receptors mediating electrolyte channels (Na+, Cl−, Ca2+) atsynapses, so that synaptic transmission is hampered. In addition, halogenated inhala-tional agents and ketamine appear to hinder axonal conduction. As a result, themajor anesthetic impact on neurological pathways used for monitoring appears to be atthe synaptic connections, with an additional minor component based on the lengthof the pathway. Varying locations of action as well as differences related to drugdosage make marked differences between agents when related to motor-evokedresponses. Further, neurological disease appears to make the responses more diffi-cult to record under anesthesia, increasing the challenge of monitoring in the verypatients where it may be most important.



452 Tod B. Sloan

1 INTRODUCTION

The anesthesia that is used during surgery where motor evoked potential(MEP) monitoring is used can markedly affect the ability to record some typesof responses. This review will focus on both the theory and practical aspects ofthese anesthetic agents. In theory, the type of interaction between the anesthe-sia and the motor responses should be predictable from knowledge of the mech-anism of action of the anesthetic drugs involved. Unfortunately, we do not havea thorough understanding of the mechanism of anesthesia, but the major targetfor anesthetic action appears to be at neural synapses, especially the gaba aminobutyric acid (GABA) and n-methyl-d-aspartic acid (NMDA) receptors, whichmediate electrolyte channels (Na+, Cl−, Ca2+). Hence synaptic transmission ishampered. In addition, ketamine appears to hinder axonal conduction. As aresult, these two effects suggest that the major anesthetic impact on neurolog-ical pathways will be at synaptic connections, with an additional minor com-ponent based on the length of the pathway [1]. This is consistent with theobserved effects (see following text) and is corroborated by the observation thatmuscle recorded responses from transcranial magnetic stimulation are alteredby anticonvulsant medications that do not produce anesthesia [2] but producepostsynaptic enhancement of GABA receptors. Different anesthetic agents pro-duce unique effects, depending on the specific locations of anesthetic action,drug type, and drug potency. Finally, the presence of neurological disease mayenhance the effects of anesthesia drugs as well as change the relative effects ondifferent pathways. As discussed in following text, providing anesthesia duringmonitoring of the motor pathway can pose a very significant challenge for theanesthesiologist in the very patients where it may be most important.

2 OVERVIEW

Since the anesthetic effects will vary with the methodology, it is important toreview the three basic techniques that have been employed to attempt moni-toring of motor tracts. The first technique involves stimulation of the motorcortex using transcranial electrical (tcEMEP), direct cortical electrical, or tran-scranial magnetic stimulation (tcMMEP). The descending electrical volley inthe motor tracts that is produced can be measured in the epidural space or byrecording the compound muscle action potential (CMAP) produced in themuscles (“myogenic” responses). The second method involves the stimulationof the spinal cord by epidural or percutaneously placed perispinal electrodesand recording in the muscles or in the peripheral nerves (“neurogenic”responses). One popular technique of spinal stimulation has been pioneered byOwen [3] and has been termed the “neurogenic motor-evoked potential”


Anesthesia and Motor Evoked Potential Monitoring 453

(NMEP), based on early experiments that suggested that the response so mea-sured was a motor tract response. As discussed in the following text, this technique(as with any form of spinal stimulation) is probably the result of stimulation ofboth sensory and motor tracts and therefore may not be an appropriate tech-nique for monitoring pure motor tracts. Recent reports by Minahan and col-leagues show that this technique monitors only the functional integrity of thedorsal columns [4, 5]. To date it is believed that transcranial motor evokedpotentials (tcMEP) by electrical or magnetic stimulation produce a pure motortract response. The third technique of motor monitoring involves stimulationof the peripheral motor system such as the nerve roots (as with pedicle screwmonitoring) or the use of reflex arcs synapsing in the caudal spinal cord.

For motor cortex stimulation (transcranial or direct), two basic mechanismsproduce a descending electrical volley. First, they produce a direct activation ofthe pyramidal cells producing a D (direct) wave. Second, activation of inter-nuncial pathways produces a series of I waves that follow the D waves down thedescending motor pathways in 1.3 to 2.0 ms intervals. D waves appear to orig-inate from the trigger zone of the motor cortex pyramidal cells by direct stim-ulation, whereas I waves appear to be produced by transsynaptic activation oftangentially oriented corticocortical interconnections of lamina V as well ascorticocortical projections from the precentral and premotor cortex. Since mag-netic stimulation induces a tangentially oriented electric current in the brain,weaker magnetic stimulation may preferentially produce I waves. Hence,although electrical and high-magnetic-field impulses directly stimulate thepyramidal cells, weaker magnetic impulses appear to depend on synaptic acti-vation for production of a response.

Since no synapses are involved, the production of D waves will be relativelyimmune to anesthetic effects on the motor cortex. However, since the produc-tion of I waves involves synapses, the production of these waves will be reducedwith anesthetic agents that depress synaptic function. The situation may be abit more complex, since synaptic function (and the ability to activate I wavesvia synaptic stimulation) is probably the result of a delicate balance of inhibitoryand excitatory influences from adjacent neural pathways. Therefore, it is pos-sible that anesthetic agents that block inhibitory influences may lesson the anes-thetic impact by making internuncial synapses more easily activated. Likewise,anesthetics that block excitatory influences may worsen the anesthetic impactat the internuncial synapses.

Once activated, the electrical responses that travel down the spinal cordreach the α-motoneuron, where, after sufficient stimulation has occurred, aperipheral nerve response results. For a single stimulation of the motor cortex,D and I waves both appear necessary for bringing the α-motoneuron to firingthreshold for production of a peripheral nerve response. Likewise, techniquesthat involve stimulation of the spinal cord or sensory reflex arcs will also traverse


454 Tod B. Sloan

the α-motoneuron. Methods that involve stimulation of the nerve root or motorcomponent of the peripheral nerve will not involve this synapse. As the secondsynaptic system in the motor pathway, corticospinal tract (CT) α-motoneuronssynapse in a location potentially susceptible to anesthetic effects. Anestheticaction here may have two effects. First, partial synaptic blockade may com-pound a loss of I waves, making it more difficult for cortical stimulation tobring the α-motoneuron to firing threshold. This may explain why cortical stim-ulation with weak magnetic fields (tcMMEP) is more susceptible to inhalationalanesthesia than is electrical stimulation (tcEMEP). At higher anesthetic doses,synaptic blockade may inhibit synaptic transmission regardless of the compo-sition of the descending spinal cord volley of activity.

Of note is that stimulation of the pathways that lead to peripheral motorresponse (peripheral sensory stimulation or stimulation of the sensory path-ways of the spinal cord that result in descending antidromic volleys) may passthrough other synapses and thus make the anesthetic effects more complex.Likewise, anesthetic effects that alter the excitatory or inhibitory influences onthe α-motoneuron may also alter the anesthetic effect on the α-motoneuron.

One method that has somewhat overcome the anesthetic effect at theα-motoneuron is multipulse stimulation of the motor cortex. In this case, mul-tiple D waves are produced such that anesthetic depression of the internuncialpathways in the cortex has little effect. Thus, for this technique, the major anes-thetic effect may be at the α-motoneuron. This may allow better myogenicresponses at low anesthetic doses. However, at higher doses of anesthetics,these multiple D waves may be insufficient to overcome the depression effec-tively blocking the response. Clearly, the interstimulus interval of the multi-pulse stimulation will also interact with the effectiveness of the technique. Withwidely spaced stimuli, decay of the effect at the α-motoneuron may preventeffective summation. With closely spaced stimuli, the cortical neurons maynot have recovered effectively from the previous response to produce an ade-quate response to subsequent stimuli. Hence an optimal interstimulus inter-val (ISI) should be found. It is possible that anesthetic influences may alterthe optimal ISI if they alter the recovery characteristics of the motor cortex orspinal cord for the production of spinal cord responses. The same is true ifanesthetic influences alter the decay characteristics of the α-motoneuron thateffect summation.

The third major synaptic location for anesthetic effect in the motor pathwayis at the neuromuscular junction. Fortunately, with the exception of neuro-muscular blocking agents and drugs that alter acetylcholine transmission, anes-thetic drugs have little effect at the neuromuscular junction. The converse isalso true, since neuromuscular blocking agents have little effect in synaptictransmission and axonal conduction in motor pathways other than at the neu-romuscular junction. This means that neuromuscular blockade will need to be



carefully controlled when myogenic responses are monitored. Finally, it shouldbe noted that anesthetic drugs might have an indirect effect on motor-evokedresponses by virtue of alterations in the physiological factors that provide nutri-ent supply to the neural tracts. For example, anesthetic agents typically lowerblood pressure, which can contribute to neural ischemia and alteration in motorresponses. Similarly, anesthesia or anesthetic management can cause changesin cerebral or spinal cord blood flow through changes in vascular tone medi-ated by the anesthetic directly or through carbon dioxide and tissue pH. Ofinterest is that synaptic function may be the most highly vulnerable region ofthe neural tracts to ischemia and physiological changes because of its highdependence on energy metabolism.

3 EFFECTS OF SPECIFIC ANESTHETIC AGENTS

Given this theoretical background, we can review the effects of individualagents on the various components of the motor-evoked responses. Since agentsmay differ as to which synaptic transmitter they interact with, the actual effecton the evoked responses may also differ. Further, as already stated, if they inter-act primarily at excitatory or inhibitory responses, they may produce a spectrumof effects at different concentrations due to changes in the balance of excitatoryand inhibitory contributions to the motor pathway. Since the electroen-cephalogram (EEG) is produced by synaptic activity, the effect of anestheticdrugs on MEP often parallels the effects on the EEG [6, 7].

3.1 HALOGENATED INHALATIONAL AGENTS

The most common anesthetics in use today, the halogenated inhalational agents(desflurane, enflurane, halothane, isoflurane, sevoflurane), have been exten-sively studied with motor-evoked responses [8–17]. These agents producesynaptic inhibition as revealed by reduction in frequency and amplitude in theEEG until electrocerebral silence occurs. As such, one would predict anestheticdepression at the α-motoneuron as well as in the internuncial neurons of themotor pathway. Depression of the neuromuscular junction does not appear tobe a major effect on the MEP. These agents depress the EEG to different degreesat equipotent anesthetic concentrations. For the MEP, several studies supportdifferences in the potency of halogenated inhalational agents on transcranialMEPs. The relative order seen is isoflurane (most potent), enflurane, andhalothane (least potent) [10]. Studies with the newer agents sevoflurane anddesflurane suggest that these agents are similar to isoflurane at steady state.However, because of their more rapid onset and offset of effect (because of their


456 Tod B. Sloan

relative insolubility), they may appear to be more potent during periods whenconcentrations are increasing. Also, because of their lower solubility, their useallows a more rapid adjustment during anesthesia (i.e., the concentration canbe raised or lowered more rapidly if needed).

Single-pulse transcranial stimulation with MEPs recorded in muscle appearsto be so easily abolished by inhalational agents that the MEPs are oftenunrecordable in the presence of these agents [9, 14, 18, 19]. When recordable,the major effect appears to occur at low concentrations (e.g., less than 0.2–0.5%isoflurane) [12, 16, 20, 21]. This effect is likely due to depression of the α-motoneuron synapse as well as loss of I waves caused by anesthetic effects inthe internuncial synapses [15, 22]. Changes in the H reflex confirm an effect ofhalogenated inhalational agents at the spinal level [23]. Figure 17.1 shows theloss of amplitude of the tcEMEP CMAP as isoflurane concentration is increasedin the ketamine anesthetized baboon.

In contrast to myogenic responses, the D response recorded from the epiduralspace is highly resistant to the effects of these agents and is easily recordable athigh concentrations [19, 20, 24, 25] and can be used for monitoring. This has sug-gested that the most prominent anesthetic effect on tcMEP is at the α-motoneu-ron level [11, 13]. However, the loss of I waves from a cortical effect may besufficient to block myogenic responses, even in the absence of anesthetic effectsat the α-motoneuron. This is because repetitive I waves appear to be necessaryfor producing myogenic responses in the unanesthetized state [26]. Figure 17.2shows the tcEMEP epidural response in a baboon as isoflurane concentrationis increased from 0.3 to 2.1%. Note that although the D wave is maintained, theI waves are lost.

FIGURE 17.1 The effect of increasing isoflurane concentrations on the compound muscleaction potential (CMAP) response to transcranial electrical motor cortex stimulation (tcEMEP) ina ketamine-anesthetized baboon. As can be seen, the amplitude decreases progressively with increas-ing concentrations.



Studies comparing tcMMEP and tcEMEP suggest that the magnetic tech-nique can be more sensitive to the inhalational agents [10], probably becausemagnetic stimulation (especially weaker field strengths) rely more on transsy-naptic activation of the CT. High-magnetic-strength tcMMEP (which producesD waves) appears to overcome this cortical difference. The difference betweentcEMEP and tcMMEP likely also relates to the type of current pulse driving themagnetic coil. Since biphasic or rapidly attenuated sine wave pulses may bemore effective than monophasic pulses, anesthetic effect may be more pro-nounced in the latter technique [27, 28].

Because the D wave is resistant to anesthetic depression, the anestheticeffect at the α-motoneuron can be partially overcome at low concentrations bymultiple-pulse transcranial stimulation [33, 34]. In this circumstance the mul-tiple D waves formed (and I waves if produced) summate at the α-motoneuron,resulting in a peripheral nerve and motor response when cortical stimuli areplaced at an ISI interval of 1–2 ms optimally, but also effectively to 10 ms [33].Alternatively, the anesthetic effect can also be partially overcome by activationof the H reflex through peripheral nerve stimulation combined with transcra-nial stimulation [35]. Hence, low concentrations of inhalational agents appearacceptable when high-frequency transcranial stimulation is used (trains of stim-uli with ISI of 2–5 ms [29, 30]). As predicted, higher concentrations of theseagents eliminated the myogenic responses from this stimulation. Clinical expe-rience (noted in following text) suggests that avoiding the inhalational agentsmay still be desirable for monitoring during high-frequency stimulation [30].It appears that the total intravenous anesthesia (TIVA) technique also may pro-duce superior responses with high-frequency stimulation [30–32].

As indicated previously, the optimal interstimulus interval may vary with theanesthetic effect [36]. This has been noted with isoflurane and is depicted in

FIGURE 17.2 The effect of increasing isoflurane concentrations on the epidural response to tran-scranial electrical motor cortex stimulation (tcEMEP) in a ketamine-anesthetized baboon. Note thatalthough the D wave is maintained, the I waves are lost.


458 Tod B. Sloan

Fig. 17.3, which shows that a relatively broad ISI (1–5 ms) is effective at lowconcentrations (0.2% isoflurane); however, a wider interval appears better athigher concentrations (e.g., 4–5 ms at 0.4–0.6% isoflurane). At even higherconcentrations (1% isoflurane), the most effective ISI was 1 ms. These data sug-gest that if inhalational agents are used with the multipulse technique, a “tuning”of the stimulation ISI may improve the effectiveness of the monitoring.

Studies with spinal or epidural stimulation show minimal effects of anes-thesia on neurogenic or myogenic responses, suggesting that the neurophysi-ology of the electrical activity arriving at the α-motoneuron is different thanfrom cortical stimulation [3, 37]. However, the anesthetic effects in the spinalcord at all of the synapses involved (sensory and motor pathways) may changethe mixture of orthodromic motor and antidromic sensory contributions to therecorded responses. Mochida studied the responses in the peripheral nerve andmuscle following epidural stimulation in the cat [34]. He noticed that single-pulse

FIGURE 17.3 A smoothed plot of CMAP amplitude at various combinations of isoflurane(0.2–1.0%) and interstimulus interval (1–6 ms) for dual-pulse transcranial electrical stimulation.As can be seen, the largest amplitude with low concentrations is 2–5 ms. As the isoflurane con-centration is increased, the optimal ISI increases to the higher level, and at the highest concentra-tion the largest amplitude is with an ISI of 1 ms.



stimulation produced a response that was eliminated by pentobarbitol, by low-dose isoflurane, and by posterior column transection (but not lateral columntransection). When a pair of stimuli was used (ISI 1–5 ms), a new complex inthe peripheral nerve response was seen. This complex and the CMAP wereeliminated only by high-dose isoflurane or by lateral spinal cord transection.Mochida’s study suggests that the type of spinal cord stimulation and the anes-thetic used may alter the balance of sensory and motor contributions to theperipheral nerve and muscle response of spinal stimulation. Of interest is thatthe sensory tracts were more easily stimulated than motor tracts. Recent stud-ies suggest that with isoflurane anesthesia, the motor component is preferen-tially blocked, perhaps by interaction at the synapses at the α-motoneuron orby differential effects on conduction in the spinal tracts in humans [20]. Basedon these studies, it is conceivable that spinal stimulation techniques may mon-itor a mixture of sensory and motor pathways that may change with the typeand dosage of the anesthetic agents used.

3.1.1 Nitrous Oxide

Despite its weak anesthetic profile, studies with tcMMEP [8] and tcEMEP [38]show that nitrous oxide produces depression of myogenic tcMEP. When com-pared at equipotent anesthetic concentrations, nitrous oxide produces moreprofound changes in myogenic tcMEP than any other inhalational anestheticagent [1]. Like halogenated agents, the effects on the epidurally recorded MEPare minimal.

Despite the depressant effect of nitrous oxide, it has been used with record-ing of myogenic responses, particularly when combined with opioids (“nitrous-narcotic” anesthetic technique). It has also been used to supplement intravenous-based anesthetics with opioids combined with propofol [30, 32] or etomidate[32, 39–42]. It has been used in concentrations of <52% [42–43], 50–60% [30,44–47], 60–65% [48], 65–66% [39, 40], and 70–75% [18, 25, 32]. Since nitrousoxide is rather insoluble in tissues, its concentration and the depressant effectcan be titrated rather quickly, so that if chosen as an anesthetic technique it canbe reversed rapidly [41].

Figures 17.4 (CMAP responses) and 17.5 (epidural responses) show theeffect of increasing inspired nitrous oxide from 0 to 79% on tcEMEP. The effectsappear to mimic the effects of isoflurane (i.e., loss of CMAP and decreasednumber of I waves at higher concentrations).

Studies suggest that nitrous oxide may actually be “context sensitive” in itseffects, similar to its effects on the EEG (i.e., the actual effect may vary depend-ing on the other anesthetics already present). Studies of equi-anesthetic mix-tures of isoflurane and nitrous oxide have demonstrated that the mixture has amore potent effect on cortical SSEP than would be predicted by adding the


460 Tod B. Sloan

effects of each agent [49]. This suggests that the mechanism of action of nitrousoxide may be different from that of isoflurane.

3.2 INTRAVENOUS ANALGESIC AGENTS

Since the inhalational agents and nitrous oxide are poor choices for anesthesiawhen myogenic responses of tcMEP are desired, anesthetic techniques havefocused on intravenous anesthetic agents for clinical monitoring. If the inhala-tional agents need to be completely avoided, then intravenous agents can becombined to produce a total intravenous anesthetic (TIVA). Fortunately, because

FIGURE 17.4 The effect of increasing nitrous oxide concentrations on the CMAP response totcEMEP in a ketamine-anesthetized baboon. As can be seen, the amplitude is progressivelydecreased with increasing concentrations, similar to isoflurane.

FIGURE 17.5 The effect of increasing nitrous oxide concentrations on the epidural response totcEMEP in a ketamine-anesthetized baboon. Note that although the D wave is maintained, thenumber of I waves is decreased, and their latencies are prolonged in a way that is similar to theeffects of isoflurane.



the mechanism of action of intravenous agents appears to be different than thatof inhalational agents, these agents differ in their effects on MEP such that theycan be more favorable for intraoperative monitoring.

3.2.1 Opioid Agents

Since analgesia (pain relief) is a primary component of anesthesia, the opioids(fentanyl, alfentanil, sufentanil, and remifentanil) are the intravenous agentsmost frequently chosen when inhalational agents must be avoided or used inlow concentrations. As with minimal depression of the EEG (a dose-relateddecline in frequency of the EEG in the delta range while maintaining ampli-tude), opioid effects on MEP are less than those of inhalational agents. Studieswith myogenic responses of tcMEP from electrical and magnetic stimulationshow only mild amplitude decreases and latency increases that usually permitrecording [21, 50–52]. The observed effects are reversed with naloxone, sug-gesting that this effect is related to mu receptor activity [53–55].

As with systemic opioids, the spinal application of morphine or fentanylfor postoperative pain management produces minimal changes in the H reflex[56, 57] suggesting that effects on motor-evoked responses should be minimal.In addition to having minimal effects on the motor pathways, fentanyl hasbeen suggested to be useful in reducing background spontaneous muscle con-tractions and associated motor unit potentials, which may improve CMAPrecordings.

The effects of opioids appear to be related to drug concentration, since max-imal changes occur at the same time drug concentrations peak, after bolus drugdelivery. One study of fentanyl suggests that the effect on sensory evokedresponses may be minimized by using a drug infusion to avoid transient boluseffects [58]. Remifentanil, a rapidly metabolized opioid, may be well suited foruse by infusion since its concentration and effect can be rapidly changed.

Because opioids have less effect than inhalational agents, opioid-based anes-thesia has usually been used when myogenic tcMEPs are monitored [18, 24, 25,30–32, 39, 40, 42, 44–48, 59–68].

3.2.2 Ketamine

Ketamine is a less frequently used analgesic but a valuable component of anes-thetic techniques for recording responses that are easily depressed by anesthe-sia. This is because ketamine is an excitatory agent (probably through itsinteraction at the NMDA receptor) that may heighten synaptic function ratherthan depress it. For example, ketamine produces high-amplitude theta activityin the EEG, with an accompanying increase in beta activity that appears torepresent activation of thalamic and limbic structures. It has been reported to


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provoke seizure activity in individuals with epilepsy but not in normal indi-viduals. In addition, ketamine has been reported to increase cortical SSEP ampli-tude [56] and increase the amplitude of muscle and spinal recorded responsesfollowing spinal stimulation [21, 69]. This latter effect on muscle responses maybe mediated by the same mechanism that potentates the H reflex [70].

Minimal effects were observed in myogenic tcMEP with ketamine [21, 71,72]. Muscle responses and spinal recorded responses to spinal stimulation arealso enhanced at doses that do not produce spike and wave activity in the EEG[65, 69]. As such, ketamine has become a valuable adjunct during some TIVAtechniques for recording muscle responses. In these techniques it has beencombined with opioids [42, 59, 66, 67] or methohexitol [66]. High dosages,however, produce depression of the myogenic response, which is consistentwith its known property of spinal axonal conduction block [73]. These effectshave made ketamine a valuable adjunct to anesthesia with tcMEP [74]; how-ever, its hallucinatory potential and known increase in intracranial pressurewith intracranial pathology have led to a reluctance to use it in anesthesia.

3.2.3 Sedative-Hypnotic Drugs

Intravenous sedative agents are frequently used to induce or supplement gen-eral anesthesia, particularly with opioids or ketamine, when inhalational agentsare not used. This is because fentanyl is primarily an analgesic, and, even withhigh doses, sedation, anxiolysis, or amnesia cannot be ensured (i.e., intraoper-ative awareness may be present). Although ketamine doses produce some dis-sociative effects in addition to analgesia, supplementation of ketamine withsedative drugs can reduce the risk of excitatory events, including hallucina-tions. Hence, a TIVA usually includes an opioid or ketamine for analgesia com-bined with a sedative-hypnotic agent. Like opioids and ketamine, thesedative-hypnotic agents (except droperidol) can be used by infusion to reducetransient changes in the monitored responses.

In studies where the different drugs have been compared, marked differ-ences in recording myogenic tcMEP have been observed [18, 21, 65]. In gen-eral, thiopental, midazolam, and propofol produced marked depression in bolusdoses. Because of the slower metabolism of these drugs, the authors concludedthat thiopental and midazolam were poor drugs for induction of anesthesiabecause their effects may linger into the surgical procedure.

3.2.4 Barbiturates

Popular drugs for induction of general anesthesia, barbiturates are similar toinhalational agents in their effect on the EEG, producing mild activation (fastactivity) at low doses and a depressant effect leading to burst suppression and



electrical silence at higher doses. Not surprisingly, myogenic responses of tcMEPare unusually sensitive to barbiturates. Further, the effect appears quite pro-longed; in one study, induction eliminated the tcMMEP response for a period of45–60 min [21], suggesting that barbiturates may be a poor induction choicewhen monitoring with this modality. For this reason, most anesthetic protocolsdo not use thiopental for induction of anesthesia. However, it has been suc-cessfully used in some anesthetic regimes [44, 46, 68] and given as intermittentboluses during the anesthetic [68]. Given newer, better agents (e.g., propofoland etomidate), the use of barbiturates has largely been eliminated duringtcMEP monitoring.

One exception, methohexitol, has different characteristics from thiopental.It is rapidly metabolized, so that it is short acting and rapidly titratable. In addi-tion, since it is known to enhance seizure activity at low doses, it may reducethe inhibitory influences on the motor pathway. Although not commonly used,one TIVA protocol for myogenic tcMEP successfully used methohexitol infu-sions with opioids and ketamine [66]. Fortunately, this drug is more rapidlymetabolized and appears to have excitatory properties (low doses can be usedto identify seizure foci during cortical mapping of epilepsy).

3.2.5 Benzodiazepines

The benzodiazepines, notably midazolam, have been advocated as supplementsto TIVA in routine surgery because of their excellent sedation and amnesic qual-ities (particularly to reduce the chance of hallucinogenic activity with ketamine).However, at higher doses they produce generalized slowing of the EEG into thetheta and delta range without burst suppression, suggesting marked synapticinhibition via GABA channel action. Midazolam has been used as intermittentboluses during recording of myogenic tcMEP [68], but as with thiopental, itproduces prolonged marked depression of myogenic tcMEP [51, 65, 75, 76].This has been interpreted as inhibition of cortical pyramidal cell neurons. Likebarbiturates, the benzodiazepines have not gained favor for induction or as acomponent of TIVA during myogenic tcMEP recordings.

3.2.6 Etomidate

As opposed to the barbiturates and benzodiazepines, etomidate can enhancesynaptic activity at low doses, possibly by changing the balance of inhibitoryand excitatory influences on motor pathways. At low doses (0.1 mg/kg), eto-midate may produce seizures in patients with epilepsy [77], and markedmyoclonic activity is often seen with anesthesia induction. However, at higherdoses it can produce a flat EEG. Since etomidate is rapidly metabolized, its con-centration can be rapidly adjusted to take advantage of the enhancing activity


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or reduce the depressant effects seen at high concentrations. This effect hasbeen used to enhance amplitude in both sensory and motor-evoked responses[78, 79]. Fortunately, the enhancing activity occurs at doses that are consistentwith the desired degree of sedation and amnesia needed for TIVA. Studies withtcMEP have suggested that etomidate is an excellent agent for induction andmonitoring of these modalities [21, 51, 65, 67, 80, 81]. Of several intravenousagents studied, etomidate had the least degree of amplitude depression afterinduction doses or continual intravenous infusion [21]. Latency (onset) changeswere not observed, and amplitude enhancement of muscle responses was notobserved except at high dosages [80]. Because of the prolonged effect of thiopen-tal, etomidate has been used for induction of anesthesia during monitoring [41,42, 45, 59, 67]. As a component of TIVA, infusions of etomidate have been com-bined with opioids [40, 41, 60, 67].

Figures 17.6 (CMAP) and 17.7 (epidural), showing recordings from tcEMEPwith increasing concentrations of etomidate, demonstrate that etomidate behavesdifferently than inhalational agents or propofol (see next section). Note an ini-tial increase in CMAP amplitude at low doses (an effect more prominent intcMMEP than tcEMEP) and an increase in I waves rather than a loss.

3.2.7 Propofol

As the newest sedative-hypnotic agent, propofol has been extensively studied.It produces dose-dependent depression of the EEG reminiscent of the barbitu-rates and can produce burst suppression and electrical silence at high doses.This is consistent with the postulated site of anesthetic action of propofol on thecerebral cortex [82]. However, the drug is very rapidly metabolized, so that the

FIGURE 17.6 The effect of increasing doses of etomidate on the CMAP response to tcEMEP in aketamine-anesthetized baboon. As can be seen, the amplitude is progressively decreased withincreasing concentrations, similar to isoflurane. Note an initial increase in CMAP amplitude at lowdoses.



drug concentration can be titrated down to levels compatible with adequateTIVA and MEP recording. Studies with tcMEP have demonstrated a depressanteffect on myogenic response amplitude, also consistent with a cortical effect[51, 65, 83]. As a component of TIVA, induction of anesthesia can includepropofol [30], and infusions of propofol have been combined with opioids[30–32, 48]. Not unexpectedly, propofol has been used in tcEMEP when therecordings are epidural [13].

Figures 17.8 (CMAP) and 17.9 (epidural) show recordings from tcEMEPwith increasing concentrations of propofol. Note that the pattern is similar tothat of inhalational agents, with loss of CMAP and decrease of the number ofI waves at higher concentrations.

FIGURE 17.7 The effect of increasing doses of etomidate on the epidural response to tcEMEP ina ketamine-anesthetized baboon. Note that although the D wave is maintained, the I waves are lost(similar to isoflurane). Note an increase in I waves rather than a loss.

FIGURE 17.8 The effect of increasing doses of propofol on the CMAP response to tcEMEP in aketamine-anesthetized baboon. As can be seen, the amplitude decreases progressively with increas-ing concentrations (similar to isoflurane). Note the pattern is similar to that of inhalational agents,with loss of CMAP at higher concentrations.


466 Tod B. Sloan

3.2.8 Droperidol

Droperidol has little effect on the EEG when used alone. However, it is knownto lower seizure threshold, probably by dopamine antagonism. It does notappear to produce neuroexcitatory phenomena or induce seizures in epilepticpatients. When combined with fentanyl (“neurolept anesthesia”), it increasesEEG alpha activity at low doses. At higher doses, it produces high-amplitudebeta and delta activity. It appears to have minimal effects on myogenic tcMMEPwhen combined with opioids [60, 65]. However, since its effect is long-lasting,it is not suitable for use by infusion, and many anesthesiologists would preferto use a more rapidly metabolized sedative hypnotic for TIVA.

3.3 MUSCLE RELAXANTS

Since muscle relaxants have their major site of action at the neuromuscularjunction, they have little effect on electrophysiological recordings that do notderive from muscle activity. In fact, they may improve or be essential for sometypes of recordings where the muscle activity near the recording electrode maybe unwanted noise. This is true for epidural or peripheral nerve recordingswhere the activity of overlying muscle obscures the response from transcranialor spinal stimulation. For recording of epidural or neurogenic responses, com-plete or near complete neuromuscular blockade is highly desirable [25, 61].Figure 17.10 shows recording from the epidural space from tcEMEP with(below) and without (top) muscle relaxation. Note that the muscle artifactobscures the identification of I waves.

FIGURE 17.9 The effect of increasing doses of propofol on the epidural response to tcEMEP in aketamine-anesthetized baboon. Note that the pattern is similar to that of inhalational agents, withdecreased number of I waves at higher concentrations.



Certainly, complete neuromuscular blockade will prevent recording ofmuscle responses (CMAPs) during MEP recording. However, partial neuromus-cular blockade has the benefit of reducing a substantial portion of the movementthat accompanies the testing, and it may facilitate some surgical procedures inwhich muscle relaxation is needed for retraction of tissues. In these cases, care-ful monitoring of the blockade of the neuromuscular junction is critical.

Two methods are customarily used to assess the degree of neuromuscularblockade [85]. The method that best quantitates the blockade involves mea-suring the amplitude of the CMAP (T1) produced by supramaximal stimulationof a peripheral motor nerve (M response). When neuromuscular monitoring isconducted this way, successful monitoring of myogenic responses has beenaccomplished at 5–15% [61], 10% [63], 10–25% [64], 10–25% [47], 20% [40,41, 45, 59, 60], 25% [42], and 30–50% [24, 43, 67] of T1 compared to baseline.Clinically, anesthesiologists often assess neuromuscular blockade by countingthe number of twitches resulting from four motor nerve stimuli delivered at arate of 2 Hz (called a train-of-four response). Measured this way, acceptableCMAP monitoring has been conducted with only two out of four responsesremaining [31, 48]. For comparison of the two techniques, only one responseof four is present when T1 is less than 10%, two twitches are present at 10–20%,and three twitches at 20–25% of the baseline T1 response [84]. When intenseneuromuscular blockade is required (e.g., recording of epidural or neurogenicresponses), T1 response less than 10% [85], or no more than two out of fourtwitches [37], has been recommended.

Many clinicians use closed-loop control systems to monitor the twitch andcontrol the infusion so that excessive blockade does not eliminate the ability torecord or mimic loss of the response with neural injury [40, 43, 60, 64, 86, 87].

FIGURE 17.10 Recordings from the epidural space from tcEMEP with (below) and without (top)muscle relaxation. Note that the muscle artifact obscures the identification of I waves.


468 Tod B. Sloan

Because of varying muscle sensitivity to muscle relaxants, the neuromuscularblockade may need to be evaluated continuously in the same muscle groupsused for monitoring. It is important to note that the use of neuromuscularblockade is controversial during monitoring of muscle responses from mechan-ical stimulation of nerves, and partial paralysis may reduce the ability to recordthese responses (e.g., facial nerve monitoring or monitoring for pedicle screwplacement).

Although recording of myogenic responses is possible with partial neuro-muscular blockade, the amplitude of the CMAP will be reduced by the block-ade. Studies suggest that the actual reduction varies from a linear reductionparalleling the percent T1 effect to a slightly decreased rate of reduction [88,89]. As a consequence of the amplitude reduction, the ability to record withpartial neuromuscular blockade will be dependent on other factors that reducethe myogenic response amplitude, such as anesthesia or neurologic disease.Hence, amplitude reduction with initially small responses or with anestheticchoices that markedly reduce amplitude may make the use of blockade moredifficult. Fortunately, the CMAP amplitude is usually quite large. It is alsoimportant to recognize that the use of amplitude criteria for warning of impend-ing neurological injury may not be possible because inevitable fluctuations inthe degree of blockade may obscure the application of strict criteria.

4 CONCLUSION: ANESTHETIC CHOICE FOR MOTOR TRACT MONITORING

These studies suggest that for monitoring of epidural D responses from tran-scranial stimulation, the sole anesthetic consideration is the use of adequatemuscle relaxation to prevent paraspinal muscles from obscuring the epiduralrecordings. Because of its resistance to anesthesia, the D wave response shouldbe remarkably stable if the anesthetic state fluctuates so that both amplitude andlatency criteria are usable for determining neurophysiological change. If main-tenance of I waves is desired, then the anesthetic choices are limited, as dis-cussed in the previous text for recording of myogenic responses. To date, the useof I waves has not been described, although their loss might be indicative ofischemia in the motor cortex.

Anesthesia for monitoring of peripheral muscle responses to spinal cordnerve root stimulation should also be unaffected by anesthetic choice, with thesole exception of neuromuscular blockade. If the responses are dependent onsensory tract stimulation (e.g., monitoring of reflex activity through the spinalcord), then anesthetic choice must consider the effects on the α-motoneuronand the synapses involved in the pathway.



Anesthesia choice for recording of neurogenic or myogenic responses fromspinal stimulation has been described clinically. Neuromuscular blockade isclearly important (as with epidural recording) to reduce the influence of over-lying muscle activity. The studies presented here, particularly those of Mochida[34], suggest that anesthesia may play a very important role in determining thecontributions of sensory and motor pathways to monitoring responses follow-ing spinal stimulation. Since the type and intensity of stimulation may varybetween different clinically used protocols, it is difficult to make anesthetic rec-ommendations that would allow preferential recording of motor tract responses.

Clearly, the choice of anesthesia makes a marked difference in the ability torecord myogenic (and presumably neurogenic) responses following transcra-nial stimulation of the motor tracts. Because these responses are exquisitelysensitive to a large variety of anesthetic agents, it appears that the best techniquefor monitoring is a total intravenous technique. Current drug combinationsusually include opioids with ketamine, etomidate, or closely titrated propofolinfusions [30, 31, 66, 40–42, 59]. Although neuromuscular blockade reducesthe amplitude of the muscle response, a controlled degree of blockade (10–20%of single twitch remaining, or two out of four twitches remaining in a train-of-four response) is highly desirable to reduce patient motion and facilitate someprocedures. A tightly controlled muscle relaxant infusion is needed to accom-plish this to avoid excessive blockade, which would hamper monitoring. In thecircumstances of anesthetic and neuromuscular blockade reduction in ampli-tude, the amplitude of the myogenic response will inevitably fluctuate duringthe procedure. Hence, warning criteria may need to be less dependent on ampli-tude and more dependent on onset-latency or the simple presence or absenceof the response.

Perhaps newer transcranial stimulation or response facilitation techniqueswill allow a more liberal anesthesia use. Although high-frequency stimulationwould appear to allow the use of depressant agents (notably, low-dose inhala-tional agents), the authors of clinical studies using this technique recommendTIVA. Clearly, this is an area of anesthesia and monitoring that awaits advancesto allow for a wider application of this monitoring technique.

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475

1-methyl-4phenyl-1,2,3,6-tetrahydropyridine(MPTP), 410

Aα-motoneuron

anesthetic effects on, 368, 454excitability level of, 42, 44, 47and corticospinal tract, 15, 18, 28, 211

Abducens nerve, 271Abductor hallucis brevis, use in recording

MEPs, 42Abductor pollicis brevis, use in recording

MEPs, 41AC-PC, 425tAC/PC line, 424, 427, 431, 438fACA, 351, 387, 393Accessory nerve, palsy of, 189Acoustic nerve, 292, 303, 309Acoustic tumor, 295, 298, 304, 315Adamkiewicz’s artery, 137Affective disorders, 406Albe-Fessard, 408Alfentanil, effects on intraoperative

monitoring, 461Amplification

differential, 420–421impedance testing and, 421preamplification, 420–421referential, 420

Amplitude gradient, 157, 158f, 160–162Amytal test, for spinal cord ischemia,

130–132Anal M wave, 204fAnatomic target, 406Anesthesia

agents of, 238, 241, 455–468and [alpha]-motoneuron synapses,

454and bipolar cortex stimulation technique,

389–390effects on intraoperative monitoring,

31–34, 238–239, 389effects on motor cortical stimulation,

453–454effects on neuromuscular junction,

454–455effects on spinal stimulation, 452–453electrode montage in, 30f, 31–33halogenated inhalational agents,

455–458intravenous agents, 459–466methods of, 79for motor techniques, 248–249muscle relaxants, 466–468nitrous oxide, 459–460target for action of, 452

Aneurysmal bone cysts, embolization therapyfor, 136

INDEX

The letter f appended to a page reference indicates a figure; the letter t refers to a table.

Deletis_Index 6/13/02 12:51 PM Page 475

AneurysmsMEP monitoring in surgery for, 385–387,

385f, 386fSEP monitoring in surgery for, 350–351,

351t, 385value of intraoperative monitoring in,

390–391Angiography

anatomy for, 133–134anesthesia for, 135of dural/extradural lesions, 137–140of intradural lesions, 140–147neurophysiological monitoring and, 35–147of vascular tumors, 135–136

Anodal stimulation, 9, 369Anorectum, innervation of, 200–201Ansa lenticularis (AL), 429Anterior spinal artery (ASA)

effects on MEP’s, 121–122, 123fand angiographic evaluation, 135–136,

141f, 144fArteriovenous malformations (AVMs)

MEP monitoring in surgery for, 380–382value of intraoperative monitoring for, 392

Arteriovenous malformation (AVM), 123f,130–141, 140–142, 143f

Ascending cervical artery, 134Ascending occipital artery, 134Ascending pharyngeal artery, 134Astrocytoma

appearance of, 65case studies of, 85, 88clinical presentation of, 57diagnosis of, 58, 62–63fincidence of, 56, 57fin midbrain, 274–275, 280–281fprognosis after surgery, 68surgical treatment of, 65–66, 274–275

Auditory nerve monitoring, 292directly from cochlear nucleus, 306, 307f,

308directly from exposed nerve, 305–306, 306felectrode placement for, 303filtering for, 304–305interference reduction in, 302–303rationale for, 301stimuli for, 303techniques for, 301–302

Auditory-vestibular nerve, mapping of,313–314

BBaclofen, to treat spasticity, 101, 103Barbiturates, effects on intraoperative

monitoring, 462–463Basal ganglia surgery

history of, 407theoretical basis for, 410–412, 410f

Benzodiazepines, effects on intraoperativemonitoring, 463

Bilateral lateral sacral artery, 134Bilateral supreme intercostal artery, 134Bipolar cortex stimulation technique

advantages and disadvantages of, 365adverse effects of, 388anesthesia and, 389–390applications of, 364–365cortical mapping by, 364recording in, 364, 367tstimulation in, 363, 367tsubcortical stimulation by, 364–365

Blocked impulsescharacteristics of, 5f, 6–8from cord trauma, 8, 9f

Border cell, 428–429Brachial plexus, 108, 118, 154, 185Brain shift, 379, 432Brainstem

anatomy of, 269–271, 271fentry routes into, 272ftumor localization in, 272–274

Brainstem auditory evoked potentials (BAEPs)

allowable variation in, 308–309enhancement of, 304ffiltering of, 304–305monitoring of, 309recording of, 301–305

Brainstem lesion surgeryanatomic background for, 270approaches to, 274–279complications of, 284–285dangers of, 272–273, 273fhistory of, 268–269neurophysiological monitoring in,

285–286patient selection for, 269postoperative care in, 279, 284–285rationale for, 269strategy for, 269–274

476 Index


Brainstem mapping (BSM)anesthesia in, 322case study of, 328, 329f–330f, 331, 331f,

332f, 333f, 334fclinical application of, 331–332clinical limitations of, 327described, 320, 321femergence of, 320results of, 323–324surgical implications of, 325–326, 325ftechnique of, 322

Bulbocavernosus reflex (BCR), 203monitoring of, 128–129, 211–212, 215

Burster cell, 428f, 436f

CCampotomy, 407Carotid artery, 341Cathodal stimulation, 7, 10, 369Cavernomas, 393Cavernous malformations, 142

diagnosis of, 56surgical treatment of, 67

Cavitron ultrasonic aspirator, 60–61Central sulcus, localization of, 354, 355f, 356,

357fCentral tumors

difficulties posed by, 392–393MEP monitoring in surgery for, 380–382SEP monitoring in surgery for, 352–353value of intraoperative monitoring in

surgery for, 394Cerebral palsy

baclofen to treat, 103classification of, 103intraoperative sacral monitoring in,

212–216MDT to treat, 104outcome assessment for, 226–228rhizotomy to treat, 95, 96f, 103SDR rhizotomy to treat, 94–95, 96f, 219–228

Cerebrospinal fluid, postsurgical leakage of,69–70

Cervicomedullary junction, 121, 279, 282fCervicomedullary tumors, cranial nerve motor

nucleus displacement by, 323, 324f, 326,326f

CMAPs (compound muscle action potentials),28, 220

intraoperative use of, 221–223

monitoring in pedicle screw placement,240–241

CNAPs (compound nerve action potentials),170, 183f

anesthetics and, 182characteristics of, 184electrodes for recording and stimulating,

178–181evaluation of, 183–185to grade nerve injury, 185–187intraoperative recording of, 182–183,

187–190in spinal nerve injuries, 185

Cochlear nucleus, 301, 306f, 308Common mode rejection ratio (CMRR), 421Conducted impulses

characteristics of, 5–6, 5fgeneration of, 8–12, 155

Constant current, 76, 243–244, 245f, 373f Constant voltage, 244, 245f, 294, 423tContact laser, 60, 63–66Cooper, 407Corpus striatum, and Parkinson’s disease,

411Cortical mapping

using MEP mapping, 366using Penfield’s technique, 364

Corticobulbar tract, 327, 328fCorticospinal tract (CT) waves, 4–5

D waves, 5–6, 5fI waves, 5f, 6monitoring, 7–8stimulus intensities and, 10f

Cranial motor nerve monitoring benefits of,315

of CN III, IV, VI, 298–299of CN IX–XII, 299–300of facial nerve, 293–298risks of, 300of trigeminal nerve, 298

Cranial motor nerves, displacement by tumor,323, 324f

Cranial nerve III, motor portion of,monitoring of, 298–299

Cranial nerve IV, monitoring of, 298–299Cranial nerve VI, monitoring of, 298–299Current shunting, 252, 253f, 294CUSA, 59, 65–66, 89Cystoprostatectomy, adverse effects of,

203–204

Index 477


DD volley, 18D waves, 5–6, 5f, 75

anesthesia and, 453desynchronization of, 40–41, 41feliciting, 7f, 8–12, 15f, 76factors influencing recording of, 37–38, 39f,

40, 40fgeneration of, 45–46, 47finterpretation of, 82–83latency of, 43neurophysiology of, 76–77number of, 44–45recording, 7–8recording using single-pulse TES, 34–36recovery of, 42–43, 42fsite of, 9

Deep brain stimulation (DBS), 408advantages of, 408studies on, 409

Deep cervical artery, 134Dermatomal SEPs (DSEPs), 236–237

to aid pedicle screw placement, 255–259Desflurane, effects on intraoperative

monitoring, 453Desynchronization, 8, 40, 41f, 82Differential amplifier, 421Direct electrical stimulation, 251, 368Direct nerve root stimulation, of MEPs, 243–244Direct pathway, 410f, 411Distal cubital tunnel syndrome, 189Dorsal columns

mapping of, 157, 158f, 161f, 163fmidline determination, 154, 164

Dorsal hornelectrode recordings of, 105, 110–111surgery on. See MDT

Dorsal rhizotomy. See Posterior rhizotomyDorsal root entry zone (DREZ), 97, 98f

indications for surgery on, 113–114laser surgery on, 112microsurgery on. See MDT (micro-

DREZotomy)RF thermocoagulation in, 111–112ultrasonic procedures on, 113variations in, 107f

Dorsospinal artery, 134Double crush syndrome, 189DRAPs (dorsal root action potentials)

elicitation of, 206

of pudendal nerve, 203, 207–208, 209f, 210, 215

Droperidol, effects on intraoperativemonitoring, 466

Dural/extradural vascular malformationsangiography of, 137treatment of, 137, 139–140types of, 137

Dystonia, 406globus pallidus procedures to treat, 427

EEEG (electroencephalography)

intraoperative use of, 27Eighth nerve, 306, 308Electrical noise

compensating for, 190–191sources of, 191–192

Electrodespercutaneous placement of, 36–37placement after laminectomy or flavectomy,

37for recording D and I waves, 34–36,

39f, 40ffor peripheral nerve monitoring, 178–181for recording, 418–420, 420ffor sacral monitoring, 207

EMG (electromyography)of facial nerve, 295–298for intraoperative monitoring, 5, 108origin of, 27

Endovascular embolizationanatomy for, 133–134angiographic evaluation for, 135–137indications for, 133for tumors, 135–136, 140f–141ffor vascular malformations, 137–147

Enflurane, effects on intraoperativemonitoring, 455

Entrapment neuropathy, assessment for, 189Ependymoma

appearance of, 65case study of, 87clinical presentation of, 57diagnosis of, 58, 59–61fincidence of, 56, 59fin midbrain, 282f–283fprognosis after surgery, 68surgical treatment of, 66–67

Epidural electrode, 35, 38, 80, 157, 206

478 Index


Epidural MEPs, 76–77, 373Epilepsy, stimulation mapping and, 357, 359,

361–362Erectile dysfunction

diagnostic testing of, 202–203neurogenic causes of, 201–202

Essential tremor, 406Ethanol, as embolic agent, 136Etomidate, effects on intraoperative

monitoring, 463–464, 464f,465fExtraoperative function mapping with grid or

multiple-strip electrodesindications for, 357–358using stimulation technique, 361–362techniques for, 358–360types of, 358

FFacial nerve monitoring, 292

goals of, 293–295neural conduction, 297recording EMG potentials, 295–298

Fentanyl, effects on intraoperative monitoring,461

Fibrillary astrocytoma, incidence of, 57fFifth nerve, 311Filtering, 301–305, 367tFirst dorsal interosseus muscle, 14–15Flavectomy, electrode placement after, 37Flavotomy, electrode placement after, 37Floor of fourth ventricle

mapping of, 310–311, 310f, 315recording from, 306, 307f, 308stimulation of, 323–324

Fluoroscopy, 62, 232Forearm flexors, use in recording MEPs, 42Forel’s Field H (H2), 434–435Functional Inventory Measure for Children

(WeeFIM), 227–228Functional mapping, 353–354

extraoperative, with grid or multiple-stripelectrodes, 357–362

intraoperative, of motor cortex and whitematter, 362–365

SEP phase reversal in, 354–357

GGanglioglioma

appearance of, 65case study of, 85, 87

diagnosis of, 58incidence of, 56, 57fsurgical treatment of, 65–66

Giant-cell tumor, embolization therapy for,136

Glioblastomaincidence of, 57fprognosis after surgery, 68

Gliomabrainstem, 268operability of, 269

Glioma, 383f, 384fincidence of, 57finsular, 392–393prognosis after surgery, 68

Globus pallidus pars externa, cell typesof, 428

Globus pallidus pars internadeep brain stimulation of, 426and Parkinson’s disease, 411postventral pallidotomy, 426–427recording of, 428–431, 428f

Glossopharyngeal nerve (CN IX), motorportion of, monitoring of, 300

GPe, 409f, 410–411, 427–430GPi, 409f, 410–411, 425t, 426–430Grid electrode, 30f, 353, 358Ground, 176–177, 191, 343, 375

HH reflex, 28, 221, 456Halogenated anesthetic agents

effects on intraoperative monitoring,456–459, 456f, 457f,458f

types of, 455–456Halogenated inhalational agents, 456Halothane, effects on intraoperative

monitoring, 455Hamstring hypertrophy, nerve entrapment

caused by, 190Hemangioblastoma

diagnosis of, 58, 64–65fincidence of, 57fsurgical treatment of, 67vascularization of, 135

Hemangioma, embolization therapyfor, 136

Hemangiopericytomacervical spinal, 138f–139fembolization therapy for, 136

Index 479


Hemifacial spasmincidence of, 311intraoperative monitoring for, 311–313,

311f, 312fHemiplegia, MDT to treat, 100Hypoglossal nerve (CN XII), monitoring of,

300

II waves, 5f, 6

anesthesia and, 453–454eliciting by extrinsic inputs, 12–15eliciting by intrinsic inputs, 12, 15–18, 16f,

17ffacilitation of, 44, 44ffactors influencing recording of, 37–38,

39fnumber of, 44–45

Iliolumbar artery, 134Impedance, 11, 35–36, 206, 423tImpedance change monitoring, 414Impedance testing, 254, 421Indirect nerve root stimulation, of MEPs,

244–245, 247Indirect pathway, 410f, 411Insular lesions, 382, 394Insular tumors, 392–393

MEP monitoring in surgery for, 382–385Intercostal artery (ICA), 123f, 134Internal capsule (IC), 32–33, 352–353, 384f,

407, 428Internal iliac artery, 134Interstimulus interval, 15f, 43f, 128, 211,

371–372, 373fInterstimulus interval (ISI), 15f, 42, 43fIntradural vascular malformations

classification of, 140neurophysiological monitoring for,

140–141, 141f, 142f–146fIntramedullary lipoma, surgical treatment of,

67–68Intramedullary neoplasms

clinical presentation of, 55–56diagnostic studies of, 58–59epidemiology of, 56prognosis after surgery, 68–69radiotherapy for, 69surgical management of, 60–68symptoms of, 58t

Intraoperative monitoringamplification in, 420–421anesthesia and, 451–468anesthetic choice for, 468–469data organization for, 437, 448felectrodes for, 418–420EMG for, 5evolution of, 338–339flowchart for, 193indications for, 311–315macroelectrode recording in, 414microelectrode recording in, 416, 416fnoise issues in, 191, 417–418of peripheral nervous system, 175–181recording sweep speed, 192of sacral nervous system, 203–216safety of, 387–388semi-microelectrode technique in, 414–415,

415fstimulation techniques for, 422–423stimulus artifact in, 192targeting techniques in, 412–413transcranial stimulation for, 4–5troubleshooting of, 190–192value and limitations of, 390–395. See also

MEP monitoring;SEP monitoring

Intraoperative neurophysiology (ION), 26–27

Intravenous analgesics, 460–461barbiturates, 462–463benzodiazepines, 463droperidol, 466etomidate, 463–464ketamine, 461–462opioids, 463propofol, 464–465sedative-hypnotic drugs, 463

Intubation, 79–81, 207, 322Ischemia, spinal cord, 142f–143f

assessment of, 127endovascular correction of, 130–133neurophysiological findings in, 124–126preoperative procedures in, 127–129provocative testing of, 130–132,

130f, 132tsurgical treatment for, 126–133

Isoflurane, effects on intraoperativemonitoring, 455, 456, 456f, 457f, 458f

480 Index


JJuvenile pilocytic astrocytoma, incidence of,

57f

KKetamine, effects on intraoperative

monitoring, 461–462Kindling, 79

LLaminectomy

electrode placement after, 37technique for, 62–64

Laminotomyelectrode placement after, 37technique for, 62–64

Lasersin DREZ surgery, 112in spinal cord surgery, 61

Leksell, 407, 413Levodopa (L-Dopa), 407, 411–412Levodopa-induced dyskinesia, 411–412

pallidotomy as treatment for, 412Lipoma, intramedullary, 67–68Localizer box, 424fLong forearm flexors, use in recording MEPs,

42Longitudinal myelotomy, 97Lower urinary tract, neural control of, 200Lumbar artery, 134

MMacroelectrode recording, 414Macroelectrode stimulation, 426, 430, 434Mayfield, 61MDT (micro-DREZotomy)

anesthesia for, 106cervical-level operative procedure, 106–108described, 105–106effects on SEPs, 109–111, 110findications for, in adults, 101–102indications for, in children, 102–104lumbosacral–level operative procedure,

108–109microdialysis in dorsal horn during, 111radiofrequency thermocoagulation in,

111–112results of, 100–101technique of, 97, 98f, 99f, 100

to treat hemiplegia, 100to treat neurogenic bladder, 101to treat paraplegia, 97, 100to treat spasticity, 97, 100, 102

Median sacral artery, 134Medulla, and cervicomedullary junction,

279–285Medullary pyramid, 17f, 18Medullary tumor, 320, 323, 324fMedullary tumors, 280f–283f

approaches to, 279cranial nerve motor nucleus displacement

by, 323, 324f, 325, 326fMeningioma, vascularization of, 135MEP mapping

advantages and disadvantages of, 366–367applications of, 366for cortical mapping, 366recording for, 366, 367tsafety of, 387–388stimulation for, 365–366, 367t

MEP monitoring, 34–42, 367anesthesia and, 389–390, 451–468anesthetic choice for, 468–469in brainstem surgery, 285–286case studies of, 85–88clinical applications of, 376–387complications of, 80difficulties in, 88, 88felectrodes for, 375history of, 75–76, 341–342interpretation of, 82–83in pedicle screw placement, 241–247polarity of stimulus and, 369practicality of, 81–82pulse characteristics for, 371–372safety of, 80, 387–388selection of muscles for, 41–42signal filtering for, 375in spinal ischemia, 124–127, 128stimulation for, 368–369surgical decisions based on, 84, 87fsweep length and averaging in, 376techniques of, 77f, 368

MEP recording, 372, 373felectrode placement for, 375filtering of signal, 375sweep length and averaging in, 376

MEP recording using, 41–42

Index 481


MEP stimulation, 368–369intensity of, 370–371interstimulus interval for, 372polarity of, 369pulse duration for, 371pulse frequency for, 371–372site for, 369–370train stimulation rate for, 372

MEPs (motor-evoked potentials)assessment based on, 75, 80–81, 86fcharacteristics of, 376correlated to clinical outcome, 378, 378tdirect nerve root stimulation of, 243–244effects of surgical events on, 378, 379f, 380f,

381f, 382feliciting during general anesthesia, 30f,

31–33, 79epidural, 76–77, 373generation of, 45–47, 49fduring intramedullary surgery, 84–85indirect nerve root stimulation of, 244–245,

247interpretation of, 377–379, 377fmuscle, 78–79, 375–376neurogenic, 373–374neurophysiology of, 42–42, 76–79spinal generation of, 242–243, 373–374transcranial generation of, 242–243

Metastatic carcinoma, embolization therapyfor, 136

Methohexitol, effects on intraoperativemonitoring, 463

Meyers, 407Microdrive, 426Microelectrode recording, 416, 416fMicroelectrode stimulation, 13, 16, 434Midas, 62Midazolam, effects on intraoperative

monitoring, 462, 463Midbrain tumors

occipital transtentorial approach to surgeryin, 275

pterional transsylvan route of entry into, 275standard infratentorial supracerebellar

approach to surgery in, 274subtemporal transtentorial approach to

surgery in, 275Miniature multielectrode, 156, 162Mixed nerve injury, 170Motor homunculus, 408

Movement disorder surgeryamplification techniques in, 420–421anatomy of, 409, 409fdeep brain stimulation and, 408–409globus pallidus procedures, 426–431history of, 406–407impedance change monitoring in, 414indications for, 406macroelectrode recording in, 414microelectrode recording in, 414, 416fmonitoring as adjunct to, 428–431neurophysiology and, 408–409operating room environment in, 417–418,

425recording electrodes for, 418–420recording techniques for, 413–416semi–microelectrode technique in, 414–415,

415fstereotactic technique for, 424–438stimulation techniques in, 422–423STN procedures, 434–437targeting techniques in, 412–413VIM procedures, 431–434

MRIand brainstem gliomas, 268–269, 269tand brainstem hematomas, 328, 328fand central sulcus localization, 356and intramedullary tumors, 58, 59ffor intraoperative mapping, 340, 362, 412

Multiphase TES, 29–30Multiple sclerosis (MS), 101Multipulse technique, 46, 78, 458Multiunit, 414Muscle artifact, 38, 39f, 466Muscle MEPs, 78–79

interpretation of, 83optimizing signal of, 375recording of, 375

Muscle relaxantseffects on intraoperative monitoring,

467–468site of action of, 464

Myelotomy, longitudinal, 97Myogenic activity, 233, 241, 242fMyorelaxation, 79

NNBCA (n-butyl cyanoacrylate), as embolic

agent, 136, 137, 140Nd:YAG lasers, 61

482 Index


Nerve injuryclassification of, 173–174

Nerve regeneration, 174–175Nerve root stimulation, 221, 241–244

LSUMC grading of, 186t–187tnature of, 170–171partial, 170regeneration after, 174–175from trauma, 189

Neurapraxia, 297Neurinoma, vascularization of, 135Neuroablation (lesioning), 407–408, 431Neurogenic bladder, MDT to treat, 100, 101Neuromas, 172f

nature of, 170–171Neuromuscular blockade

assessment of, 466–467importance of, 469

Neuronal neoplasms, incidence of, 57fNeuropathic pain, 406Neurophysiological mapping, 353, 362, 394Neurophysiological monitoring, 66–67,

136–137Neurotmesis, 297Neurotomy, to treat spasticity, 102Nitrous oxide

effects of, 459effects on intraoperative monitoring,

459–460, 460fNoise

effects in the operating room, 417, 425feffects on the CNAP, 178effects on EMG machine, 191–192effects on intraoperative recording, 74, 301signal-to-noise-ratio, 346, 374–376

OOligodendroglioma, incidence of, 57fOpioids, effects on intraoperative monitoring,

461Optic nerve, monitoring of, 308Optic tract, and pallidotomy, 430

PPain

decision making regarding, 114spinal cord surgery to remedy, 104–114

Pallidotomycomplications of, 430postventral, 426–427

Pallidum, 407Paralysis, postsurgical, 68Paraplegia

MDT to treat, 97surgically induced transient, 48

Paraspinal arteriovenous fistula (AVF), 137Paraspinal arteriovenous malformation

(AVM), 137Paravertebral veins, 134Parkinson’s disease, 406

etiology of, 411globus pallidus procedures to treat,

426–427and Pars compacta (SNc), 410and Pars reticulata (SNr), 410, 415fSTN procedures to treat, 434–437studies on, 410VIM procedures to treat, 431

Partial nerve injury, 170Partial posterior rhizotomy, 95Pauser cell, 428f, 429Pediatric Evaluation Disability Index (PEDI),

227Pedicle screw placement

anesthesia in, 238–239, 248–249assessment of nerve root function for,

233–234CMAP recording in, 240–241complications of, 259–260current shunting and, 252, 253fdirect nerve root stimulation for,

243–244DSEPs to aid, 236–237, 237f, 255–259false negative findings of complications of,

249–253history of, 232impedance testing of, 254–255indirect nerve root stimulation for, 244–245,

245f, 247MEP monitoring in, 241–248motor path assessment techniques for,

239–248muscle relaxation and assessment of,

250–252physiologic factors and assessment of,

252–253proper placement of, 232–233, 246f, 247fSEPs to aid, 234–235, 236ftranscranial and spinal stimulation for,

242–243

Index 483


Penfield, Wilder, 26Penfield’s technique

advantages and disadvantages of, 365adverse effects of, 388anesthesia and, 389–390applications of, 364–365cortical mapping by, 364recording in, 364, 367tstimulation in, 363, 367tsubcortical stimulation by, 364–365

Perimedullary veins, 134Peripheral nervous system

electrodes for recording and stimulatingimpulses in, 178–181

injuries to, 170–174nerve regeneration in, 174–175recording of action potentials in, 175–178,

175f, 182–183Peroneal nerve entrapment, 189Phase reversal, 154, 159f, 162, 353Physiologic target, 439Plasmacytoma, embolization therapy for,

136Polarity, 5, 7, 9, 35, 155, 367tPolyvinyl alcohol, as embolic agent, 136Pons, 268–270, 276fPontine tumors

combined petrosal approach to, 276, 276f,277f–278f

cranial nerve motor nucleus displacementby, 323, 324f, 325, 325f

retrosigmoid approach to, 273suboccipital craniotomy and trans-fourth-

ventricle route to, 278–279Postcentral, 356, 362f, 366Posterior communicating artery (PCOM), 348,

351, 386fPosterior rhizotomy

functional, 95, 97fpartial, 95selective, 94results of, 95, 225–228sectorial, 94–95techniques of, 223–225

Posterior spinal artery (PSA), 121–122, 130f,132t, 133–137, 144f

Precentral, 369–370, 377f, 453Preoperative mapping, transcranial

stimulation for, 4Programmable pulse generator, 408

Propofol, 462effects on intraoperative monitoring,

464–465, 465f, 466fProstatectomy, adverse effects of, 201–202Provocative tests, 123f, 130–132, 132tPT neurons, membrane potential of, 10fPudendal SEP, 204f, 214Pudendal nerve

cerebral SEPs of, 206, 210, 215dorsal root action potentials (DRAPs) of,

203, 207–208, 209f, 210, 215spinal SEPs of, 203, 208, 210, 215

RRadicular arteries, 134Radicular veins, 134Radiculomedullary arteries, 134Radiculopial arteries, 134Radiofrequency (RF) thermocoagulation, in

DREZ region, 111–112Radiotherapy, for intramedullary neoplasms,

69Recording electrode, 7, 27, 32, 81, 158f, 181f,

191, 314, 322, 435, 466Remifentanil, effects on intraoperative

monitoring, 461Rhizotomy

functional posterior, 95, 96fhistory of, 220–223indications for, 219partial posterior, 95posterior selective, 94results of, 95, 225–228sectorial posterior, 94–95techniques of, 223–225

Rootlets, 94–99, 106, 206Roots, 94–99, 106, 206

SSacral monitoring, 203Sacral nervous system

of anorectal region, 200–201diagnostic tests of, 202–203functional anatomy of, 199–202functions of, 198of lower urinary tract, 200neurophysiology of, 224frecording techniques for, 206–207

484 Index


of sexual organs, 201–202stimulation techniques, 203–206types of problems of, 198–199

Sarcoma, embolization therapy for,136

Sectorial posterior rhizotomy, 94–95Sedative-hypnotic drugs, effects on

intraoperative monitoring, 462Segmental potentials, generation of, 155Selective functional posterior rhizotomy

(SDR), 95, 96f, 222fhistory of, 220–223indications for, 219monitoring in, 220–221, 221fresponses to, 223results of, 225–228techniques of, 223–225variations in, 222–223

Semi-microelectrode recording, 414–415,415f

Sensory cranial nerve monitoringof auditory nerve, 292, 301–308of optic nerve, 308

Sensory homunculus, 408SEP monitoring

clinical application of, 347–353to facilitate pedicle screw placement,

234–235, 236findications for, 342interpretation of, 348–350intraoperative, 27, 156, 352f, 353fwith miniature multielectrodes, 156–157,

158f, 159f, 1601f, 162, 162f, 163frecording for, 344–347safety of, 387stimulation for, 343–344technique of, 342–353

SEP phase reversalindications for, 354, 355ftechnique for, 354, 356

SEP recordingelectrode placement for, 344–345filtering in, 346signal in, 346–347sweep length and averaging in, 346

SEP stimulationduration of, 343electrode placement for, 343frequency of, 344

intensity of, 343parameters for, 344t

SEPs (somatosensory evoked potentials,SSEPs), 27, 75

dermatomal, 236–237, 255–259effect of blood pressure on, 348feffects of MDT on, 109–110, 110fgenerators of, 155and peripheral nervous system, 185in spinal cord ischemia, 125–126, 127

Sevoflurane, effects on intraoperativemonitoring, 455

Sexual organs, innervation of, 201–202Signal averaging, 302Single unit, 415f, 416f, 419Single-pulse TES, 29

D wave recording in, 34–41Spasticity

decision tree for treatment for, 102intrathecal baclofen to treat, 101longitudinal myelotomy to treat, 97MDT to treat, 97, 100, 102neurotomy to treat, 102sacral rhizotomy for, 207, 212–214

SDR rhizotomy to treat, 94–95, 96f,219–228

Speech localization, 357Sphincter muscles, EMG of, 203, 207,

210–211, 216Spiegel, 407–408Spinal accessory nerve (CN XI), monitoring

of, 300Spinal arteriovenous fistula, 137Spinal arteriovenous malformation, 137Spinal cord

angiographic vascular anatomy of,133–134

arterial systems of, 120–121, 123fdirection of blood flow in, 121dorsal columns, mapping of, 153–164ischemia of, 124–133, 142f–143fneurophysiological monitoring of,

124–133vascular anatomy of, 120–123, 122fvascular malformations of, 137–147vascular tumors of, 135–136,

138f–139fvenous systems of, 122–123

Spinal cord AVFs, 140Spinal cord AVMs, 140, 142f–146f

Index 485


486 Index

Spinal cord lesioningDREZ surgery, 97–101, 104–114indications for, in adults, 101–102indications for, in children, 102–104longitudinal myelotomy, 97posterior rhizotomies, 94–97to treat pain, 104–114to treat spasticity, 94–104

Spinal cord stimulation, 101, 125, 241, 459Spinal cord surgery

case studies of, 85–88complications of, 69–70, 74history of, 56indications for, 57–58instruments for, 60–61lasers in, 61MEP behavior during, 84–85outcomes after, 68–69techniques of, 62–68

Spinal deformities, pedicle screws to correct,232–233

Spinal dural arteriovenous fistula (SDAVF),137

Spinal-cord-to-peripheral-nerve recording,28–29

Spinal-cord-to-spinal-cord recording, 27–28Spinal roots, 199, 203, 206, 210Stereotactic, 406–407, 412–413Stereotactic atlas, 412, 426–427, 437Stereotactic frame, 407, 413, 424fStereotactic technique, 406Stimulating electrodes, 7, 39, 40f, 129, 176Stimulus artifact, 192Striae medullares, 270, 320, 328Striatum, 407, 410–411, 427Strumpell-Lorrain syndrome, 101Subcortical stimulation, using Penfield’s

technique, 364–365Substantia gelatinosa, thermocoagulation of,

111–112Subthalamic nucleus (STN)

anatomy of, 435felectrical behavior of, 434–435, 436fand Parkinson’s disease, 411, 434test stimulation of, 436–437

Subthalamic nucleus (STN), 409, 411, 425t,434–437

Subthalamotomy, 409Sufentanil, effects on intraoperative

monitoring, 461

Sugita, 61Sunderland classification, 173–174Supportive system, 42, 45Supratentorial surgery

functional mapping in, 353–367MEP monitoring in, 367–388

SEP monitoring in, 350–351Surgical instruments, 74, 179, 181Surgically induced transient paraplegia,

48Sylvian fissure, 275, 353, 356

TTarget localization, 406, 412Telangiectasias, 140TES (transcranial electrical stimulation)

compared to TMS, 13–14, 13fin general anesthesia, 31–34multiphase stimulation, 29–30, 41–47muscle responses to, 18–20, 19f, 20fnew methods of, 29–31single-pulse stimulation, 29uses of, 4

Thalamotomy, 409, 431, 473Thalamus

cell electrophysiology of, 434ventral intermediate nucleus of, 431–434

Thermocoagulation, in DREZ region, 111–112Thiopental, effects on intraoperative

monitoring, 462Thoracic outlet syndrome, plexus nerve

lesions due to, 190Tibialis anterior muscle (TA), 30f, 42, 44f, 78,

123f, 242f, 249, 251f, 375TMS (transcranial magnetic stimulation)

compared to TES, 13–14, 13fintensity-related effects of, 7, 8fuses of, 4–5

Total intravenous anesthesia (TIVA), 239,389, 457, 462

Train stimulation, 80, 372, 389Transient paraplegia, 41, 46, 47fTremor cell, 428f, 429, 432fTrigeminal nerve (CN V)

mapping of, 314–315monitoring of motor portion of, 298stimulation of, 295–297

Trigeminal neuralgia, 314Trochlear cranial nerve, 272


Index 487

UUlnar nerve entrapment, 189–190Ultrasonic aspirator, 60–61Ultrasonic DREZ sulcomyelotomy, 113Urinary tract, 198, 200

VVagal nerve (CN X), monitoring of, 300Vagus nerve, 300Vascular malformations

dural/extradural lesions, 137–140intradural lesions, 140–147SEP monitoring in surgery for, 351–352

Vascular tumorsclassification of, 135

Ventralis lateralis (VL), 13, 411, 432Ventralis oralis anterior (VOA), 432Ventralis oralis posterior (VOP), 432Ventriculography, 407, 412–413Ventrocaudal Nucleus (VC), 433Vertebral artery, 134

VIM (ventral intermediate nucleus of thethalamus)

and Parkinsonism, 431–432recording of, 432–433, 432f

W Wada test, 130Wallerian degeneration, 173

regeneration after, 174WeeFIM (Functional Inventory Measure for

Children), 227–228Wycis, 407

XXylocaine test, for spinal cord ischemia, 130,

131, 132

ZZona incerta (ZI), 433–435, 436f


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Neurophysiology for Nch