Orthostatic hypotension associated withdorsal medullary cavernous angioma

Introduction

Orthostatic hypotension (OH) is because ofimpaired reflex sympathetically mediated vasocon-striction of muscle and splanchnic vessels inresponse to orthostatic stress.OH has been reported in association with lesions

at different levels of central and peripheral nervoussystem. Brain stem lesions associated with OHinclude tumors (1–5), stroke (6), syringobulbia (7)and multiple sclerosis (8). Paroxysmal apnea andvasomotor instability have been reported in strokewith a left medullary infarction (9). It has beenspeculated that OH in brainstem lesions is becauseof interruption of descending sympathoexcitatorypathways. However, the precise distribution of thelesion in relationship to these pathways has notbeen analyzed. Neurons of the rostral ventrolateralmedulla (RVLM), including the C1 group ofepinephrine-synthesizing neurons (10), provideexcitatory glutamatergic inputs to preganglionicsympathetic neurons controlling blood pressureand are critical for the efferent vasoconstrictorcomponent of the baroreflex arc (11).

Here, we describe a patient with OH as one ofthe presenting symptom of a dorsal medullarycavernous angioma who experienced severe wors-ening of the orthostatic symptoms followingpartial removal of the lesion, which overlappedthe distribution of putative sympathoexcitatoryaxons.

Case history

A 51-year-old woman presented with a 20-yearhistory of episodic vertigo and ataxia. Last year,she had a progressive loss of coordination in theleft upper limb. She also had experienced fewsyncopal episodes prior to her evaluation. Neuro-logical examination revealed normal cranial nervefunction except for vertical nystagmus. She hadgait ataxia, but corticospinal and sensory functionswere normal. Motor and sensory nerve conductionvelocities were normal. An MRI study showed acavernous angioma located at dorsal and posteriormedulla (Fig. 1). The patient underwent partialsurgical removal of the lesion and the biopsyconfirmed presence of dilated vascular channels

Acta Neurol Scand 2009: 119: 45–48 DOI: 10.1111/j.1600-0404.2008.01050.x Copyright � 2008 The AuthorsJournal compilation � 2008 Blackwell Munksgaard

ACTA NEUROLOGICASCANDINAVICA

Idiaquez J, Araya P, Benarroch E. Orthostatic hypotension associatedwith dorsal medullary cavernous angioma.Acta Neurol Scand 2009: 119: 45–48.� 2008 The Authors Journal compilation � 2008 Blackwell Munksgaard.

Background – Orthostatic hypotension (OH) is a rare manifestationof medulla oblongata lesions that may be because of interruption ofdescending sympathoexcitatory axons. Aims – To illustrate thelocation of a medullary lesion that produced OH following resection inrelationship to the location of putative sympathoexcitatorypathways. Method – A case with dorsal medullary cavernous angiomapresenting with OH is described. The possible localization of lesionwas compared with distribution of tyrosine hydroxylase (TH)-immunoreactive axons in a comparable section of the medulla of acontrol brain. Results – The patient had marked OH after partialremoval of the cavernous angioma. Biopsy confirmed the diagnosis.The magnetic resonance imaging location of the lesion overlapped thatof TH-immunoreactive axons of the medullary transtegmentaltract. Conclusions – A restricted lesion of medullary lesion interruptingthe catecholaminergic transtegmental tract arising from thesympathoexcitatory C1 neurons of the rostral ventrolateral medullacould result in severe OH.

J. Idiaquez1, P. Araya1,E. Benarroch2

1Universidad de Valpara�so, Valpara�so, Chile; 2MayoClinic, Rochester, MN, USA

Key words: angioma; cavernous; hypotension; medullaoblongata; orthostatic

Juan Idiaquez, 4 norte 1093 depto 22 ViÇa del Mar.ChileTel.: 56-32-2975623Fax: 56-32-2975623e-mail: idiaquez@123.cl

Accepted for publication April 7, 2008

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with hemosiderin deposits. After surgery, neuro-logic examination was essentially unchangedexcept for new propioceptive sensory loss in theupper limbs and transient urinary retention. How-ever, the patient had several complications includ-ing sepsis, pneumonia and a venous thrombosis inthe right lower limb. She was essentially bedriddenfor about 6 weeks. Upon attempt to stand up shedeveloped severe orthostatic intolerance withrepetitive syncopal episodes, rendering her essen-tially unable to maintain erect posture for even fewseconds.

Autonomic studies

Orthostatic blood pressure (BP) testing was per-formed using a DINAMAP monitor (Critikon,Tampa, FL, USA); the patient was in supineposition in a quiet room. Supine BP measured after30 min of rest was 121 ⁄76 mm Hg with a heart rate(HR) of 72 beats per minute. Using a tilt table, BPafter upright tilt to 80� showed an immediate fall ofBP to 60 ⁄38 mmHg, with no compensatory changein HR. Supine norepinephrine was 82 pg ⁄ml(normal resting value: 80–446 pg ⁄ml) and ontilting increased to 120 pg ⁄ml.The HR response to deep breathing was per-

formed with the patient lying quietly and breathingdeeply at six breaths per minute (5 s in and 5 sout). The maximum–minimum HR during each10-s breathing cycle was measured and the mean ofthe differences during three succesive breathing

cycles was 14 beats ⁄min (normal age values from5th to 95th percentiles, in our laboratory, are 9.1 to30.9 beats ⁄min). Twenty-four hour continuous BPrecording showed significant inversion of circadianBP variability, with lowest supine BP (73 ⁄50 mmHg) in the morning and highest supine BP(161 ⁄91 mmHg) at night. The patient was notreferred to our laboratory prior to surgery proce-dure. Average routine ambulatory BP (patientseated) was 134 ⁄82 mmHg andHRwas 68 beats ⁄min,before surgery.Follow-up: the patient was started with mido-

drine (peripheral a-adrenergic agonist) at 2.5 mgthrice a day and fludrocortisone at 0.2 mg per day;she showed a slow improvement of her orthostatictolerance. After 6 moths of treatment, her supineBP was 130 ⁄79 mmHg and fell to 58 ⁄40 mmHgduring head-up tilt, but the patient was able tomaintain an erect posture for about 30 min. Shedid not present new syncopal episodes. Autonomicsymptom questionnaire for gastrointestinal, uri-nary and sudomotor dysfunction did not showabnormalities.

Assessment of the location of the lesion

The location of the lesions based on magneticresonance imaging (MRI) was plotted against thedistribution of tyrosine hydroxylase (TH)-immu-nolabeled axons in comparable sections of themedulla obtained at post-mortem from a subjectwith no history of neurologic disease. There wasclear overlap of the lesion with that of theTH-immunoreactive axons of the medullary trans-tegmental tract (10; Fig. 2).

Discussion

Our case confirms that restricted lesions of thedorsal medulla, in our case a cavernous angioma,may result in OH. This symptom became disablingfollowing partial resection of the lesion. Althoughsimilar observation has been previously reported incases of medullary astrocytomas (1, 3–5), heman-gioblastoma (1, 12), tuberculomas (2) and meta-static infiltration (1) or following resection of abrain stem tumors (13), our study provides the firstanatomical evidence supporting that these lesionsinterrupt putative sympathoexcitatory pathways inthe medulla. The lesion overlapped the distributionof the catecholaminergic transtegmental tract,which contains the axons of epinephrine-synthe-sizing C1 sympathoexcitatory neurons of theRVLM (10). These neurons also contain glutamateand together with non-C1 glutamatergic neuronsof the RVLM, provide tonic excitatory input to

Sag: R6.4

Mag: 1.2x

A P

512 × 512

Figure 1. Sagittal T1-weighted magnetic resonance imagingshowing the location of the lesions in the posterior caudalmedulla.

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sympathetic preganglionic neurons, controllingoutflow to resistance vessels of the muscle andsplanchnic beds, and is the critical efferent path-way for baroreflex-mediated vasoconstriction trig-gered by orthostatic stress. This tract also containsascending axons from A1 neurons (containingnorepinephrine) which are involved in stimulationof vasopressin release during baroreceptor unload-ing during orthostatic stress. As TH-immunoreac-tivity does not allow differentiation betweenepinephrine (C1)- and norepinephrine (A1)-containing axons, involvement of the ascendingA1 pathway to magnocellular nuclei of the hypo-thalamus may have contributed to orthostaticintolerance in this patient. Unfortunately, supineand plasma levels of arginine vasopressin were notdetermined in this case (11). It is also possible thatthe lesion affected lateral medullary tegmentalneurons that contribute an excitatory input to theRVLM (10). Involvement of the nucleus of thesolitary tract (NTS) is less likely to explain OH inthis patient, as NTS lesions are typically associatedwith fluctuating hypertension (11).Whereas it is possible that the presence of the

cavernous angioma per se may be the cause oforthostatic symptoms and syncopal episodesexperienced by the patient prior to surgery, thedevelopment of severe OH following surgery likelyreflects further damage of this sympathoexcitatorypathway. The impaired baroreflex activity may

also have become symptomatic at the beginning,probably as a result of deconditioning, as thepatient was bedridden for several weeks. The slowimprovement of her orthostatic tolerance, in spiteof persistent low BP on standing, possibly could bebecause of a further expansion of her cerebralautoregulation range.

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A B Dorsal transtegmentalcatecholaminergic tract

A1/C1

Figure 2. (A) Axial T1-weighted magnetic resonance imaging showing the topography of the medullary lesion. (B) Plotting of thedistribution of the lesion against a section of the normal medulla immunostained for tyrosine hydroxylase, to identify the A1 ⁄C1groups of catecholaminergic neurons and the distribution of the dorsal transtegmental catecholaminergic tract. This pathwayincludes axons of from sympathoexcitatory C1 neurons that are critically involved in tonic maintenance of sympathetic vasomotortone to resistance vessels and are the efferent components of the baroreflex. This pathway may also contain ascending axons of A1neurons that provide noradrenergic inputs to the magnocellular neurons of the hypothalamus and control release of argininevasopressin in response to baroreceptor unloading during orthostatic stress.

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