Treatment of Paroxysmal Sympathetic Storm With Labetalol

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LETTERS TO

THE EDITOR

Treatment of paroxysmal sympathetic

storm with labetalol

First described by Penfield in 1929, paroxys-mal sympathetic storm is characterised byepisodic hyperhidrosis, hypertension, hyper-thermia, tachypnoea, tachycardia, and pos-turing. It has commonly been associated withclosed head traumatic brain injury, agenesisof the corpus callosum, hydrocephalus, andsuprasellar or diencephalic tumours.1 2 Pen-field hypothesised that these sympatheticspells were caused by epileptiform dischargesin thalamic nuclei irritated by increasedintracranial pressure, thereby leading him toname this entity diencephalic autonomicseizures.2 Electroencephalograms obtainedon patients during these autonomic attacks,however, have not shown epileptic activity,and anticonvulsant therapies have not proveduseful in their treatment.2 3 Bromocriptine

and morphine have been the standardtreatments for paroxysmal sympatheticstorm, and propranolol has been shown toreduce the hyperpyrexia seen during auto-

nomic spells.3 4 In this case report, wedescribe a patient treated successfully with

labetalol, but not metoprolol, suggesting that

1 antagonism alone is not suYcient to sup-press paroxysmal sympathetic storm.

A 21 year old white man was an

unrestrained passenger in a motor vehicleaccident and developed a closed head shear

injury. He was admitted to a hospital where ahead CT showed hydrocephalus necessitat-ing a ventriculoperitoneal shunt placement.A head MRI showed abnormal T2 signal inthe corpus callosum and the dorsal midbrainconsistent with shear injury. Although ini-tially comatose, he improved to near baselineover the next few months. He was admittedto our hospital 15 months later with a shuntinfection, necessitating treatment with van-comycin, shunt externalisation, and, eventu-ally, replacement. During and after resolu-t ion of t he shunt complicat ions, hedeveloped episodes of sympathetic hyperac-tivity while under continuous monitoring inan intensive care unit. These attacks werecharacterised by (1) diaphoresis throughoutthe entire body, (2) tachycardia (heart rate140160 bpm) measured by automatedpulse oximetry or by ECG, (3) hypertension(blood pressure 170180/100 mm Hg)

measured by arterial line pressure transduc-ers or by sphygmomanometer, (4) fevers to39.1 C orally, and (5) flexor posturing. Hewas alert during these episodes, and re-

sponded to questions appropriately withdenial of any acute onset of discomfort orpain. Furthermore, these attacks were notcorrelated with periods of bladder distension(Foley catheter in place) or impaction(radiograph not suggestive of retained stool).Individual episodes lasted 510 minutes andrecurred at 510 minute intervals. Clustersof these spells would last 1 to 2 hours withmore than three clusters a day.

Multiple CSF and blood cultures werenegative. Serial head CT showed markedreduction of hydrocephalus and no brainstem abnormalitiesafter shuntcorrection.Noother intracranial pathology was noted. Plainfilms and MRI of the spine showed nomyelopathic findings suggesting autonomicdysreflexia.Abdominal andpelvic CT didnotshow any hidden masses or lesions. Toxicol-ogy screen at onset of symptoms wasnegative. Electroencephalograms obtainedduring these episodes of dysautonomia dis-closed theta and delta slowing with somesharply contoured waves, but no definite ictalor interictal epileptiform activity (figure).

Although initially treated successfully withbromocriptine (5 mg twice daily) and mor-phine (15 mg every 6 hours), he waswithdrawn from morphine with a methadone

taper at the request of his parents secondaryto concerns over addiction. He was thenstarted on metoprolol (25 mg thrice daily)with little eVect on the frequency or severity

EEG obtained during episodes of paroxysmal sympathetic storm (tachycardia with heart rate of 120 bpm) shows predominant delta and theta waves(greater on the right than on the left) with no clear epileptiform activity, indicating that these attacks are not of seizure origin.

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of the hyperautonomic episodes. Replace-ment with 100 mg labetalol twice daily led toreduction in the frequency of events to aboutone a day. Subsequent increase of themedication to 200 mg twice daily resulted ina marked decrease to less than one paroxys-mal sympathetic storm over several days. Atthe time of discharge, the patient hadreturned to his preadmission baseline.

The current observations lend support tothe prevailing view that paroxysmal sympa-thetic storm may represent disruption ofautonomic function in the diencephalon andbrainstem. Bullard has proposed that theclinical syndrome may be the result of arelease phenomenon within the brainstemand/or diencephalon from loss of overridingcortical or subcortical inhibition.3 Morerecent case studies suggest localisation to thecentral sympathoexcitatory regions includingthe paraventricular hypothalamic nucleus,lateral periaqueductal grey matter, lateralparabrachial nucleus, or rostral ventrolateralmedulla.3 Compromised autonomic neuronalintegrity centrally is not surprising in the set-ting of infection after traumatic brain injury.

Various medications can potentially beused in managing central sympathetic storm.Imidazoline agonists and specific 2 adreno-

ceptor antagonists, such as clonidine andmethyldopa,5 have recently been shown tohave sympathoinhibitory actions centrallywithin the rostral ventrolateral medulla.These agents have so far been used in thetreatment of essential hypertension, tetanus,or autonomic dysreflexia. Blockers such aspropranolol however, have long been themainstay of treatment of the hypertension,tachycardia, and hyperpyrexia associatedwith paroxysmal sympathetic storm.6 7 Thisnon-selective adrenergic antagonist actsthrough inhibition of peripheral catecho-lamine activity, and being highly lipophilic,may also exert central eVects through mem-brane stabilisation or receptor blockade.Moreover, propranolol may reduce sustainedmuscle contraction.7 Taken together, these

findings suggest that non-selective receptorantagonism is suYcient to inhibit the clinicalmanifestations of diencephalic seizures.

The present case suggests that 1 receptorantagonism alone is not suYcient to treathyperautonomia during paroxysmal sympa-thetic storm. This patient was initially placedon starting doses of metoprolol, a selective 1antagonist, with little clinical eVect in control-ling the frequency of the autonomic attacks;however, labetalol, an 1 and 1-2 adrener-gic receptor antagonist did lead to an observ-able decline in symptoms. Both sympatholyticagents were given at doses typically used ininitiating treatment of systemic hypertension,suggesting that the observed response seenwith labetalol could not be explained solely bya dosage phenomenon. Prior studies also

demonstrate that small amounts of pro-pranolol (20 mg four times a day) can achievesimilar responses to those seen with labeta-lol,6 7 further arguing against a dose depend-ent eVect. Thus, at a minimum, either 1 or2 receptor blockade, likely in addition to 1blockade, is necessary in the treatment of par-oxysmal sympathetic storm.

The discrepancy in response between me-toprolol and labetalol could result from theirdiVerent eVects on the cardiovascular systemor CNS. The 1-2 adrenergic receptorblockade by labetalol decreases blood pres-sure and heart rate through negative inotropicand chronotropic eVects, and by inhibitingrenin release. In addition, labetalol has

vasodilator properties resulting from 1blockade and partial 2 agonism. Thesereduce peripheral vascular resistance, bloodpressure, and coronary vascular resistance, apotential advantage over other blockers.Alternatively, diVerences in central activitymay explain the increased eYcacy of labetalolover metoprolol. As both agents are lipophilic,their central access should not diVer signifi-cantly; rather, diVerences in receptor antago-nism (1 versus 1, 1, 2) would more likelyexplain the therapeutic discrepancy. As pro-posed with propranolol,4 inhibition of 2receptors by labetalol may exert a stabilisingeVect within the CNS through indirectinhibition of sympathetic nerve activity.

In the present case, we report the use oflabetalol as an alternative agent in thetreatment of paroxysmal sympathetic storm.It likely exerts both a central and peripheralblockade of1 and adrenergic receptors toproduce inhibition of autonomic dysregula-tion. The clinical ineVectiveness of metopro-lol further suggests a necessary role for 2and/or 1 receptors in the clinical presenta-tion of paroxysmal sympathetic storm. La-betalol may prove an alternative equal to orbetter than morphine in the treatment ofthese spells, especially when addiction anddependency are of concern.

D DOV L SHEEN

E BROMFIELDDepartments of Neurology, Brigham and Womens

Hospital,75 Francis Street, Boston, MA 02115,USA

and Massachusetts General Hospital, Harvard

Medical School, Boston, MA, USA

Correspondence to: Dr E [email protected]

1 Penfield W, Jasper H. Epilepsy and the functionalanatomy of the human brain. 1st ed. Boston: Lit-tle Brown, 1954.

2 Boeve BF, Wijdicks EF, Benarroch EE, et al.Paroxysmal sympathetic storms (diencephalicseizures) after severe diVuse axonal headinjury. Mayo Clin Proc 1998;73:14852.

3 Bullard DE. Diencephalic seizures: responsive-ness to bromocriptine and morphine. Ann

Neurol1987;21:60911.4 Head GA. Central imidazoline- and 2-

receptors involved in the cardiovascular actionsof centrally acting antihypertensive agents.Ann

NY Acad Sci 1999;881:27986.5 Jenkins WL, Clark DR. A review of drugs

aVecting the heart. J Am Vet Med Assoc1977;171:8592.

6 Meythaler JM, Stinson AM. Fever of centralorigin in traumatic brain injury controlled withpropranolol. Arch Phys Med Rehabil 1994;75:81618.

7 Sneed RC. Hyperpyrexia associated with sus-tained muscle contractions: an alternativediagnosis to central fever. Arch Phys Med Reha-bil1995;76:1013.

Moyamoya disease presenting with

singing induced chorea

Moyamoya disease is a relatively uncommon,chronic cerebral vasculopathy of unknown

aetiology that is characterised by unilateral orbilateral stenosis or occlusion of the proximalportion of the carotidarteries, together with anabnormal vascular network at the base of thebrain. Most childhood cases manifest with thesigns and symptoms of cerebral ischaemia orinfarction, whereas intracerebral haemorrhageprevails in adults.1 2 We describe here a case ofmoyamoya disease in a 29 year old multipa-rous woman, who presented with involuntarylimb movements induced by singing.

A 29 year old woman, gravida two, para two,

presented to the neurological outpatient clinicat Chungbuk National University Hospital withrecurrent episodes of brief involuntary move-ments aVecting her left hand and arm. The

movements were characterised as unilateral,

brief,coarse, irregular, and wavering. There was

no history of neuroleptic drug therapy, or fam-

ily history of involuntary movement.General physical, neurological, and neuro-

psychological examinations were unremark-able. Baseline blood tests, ECG, and chestradiography all yielded normal results. Theepisodes of the patients involuntary move-ments were unique, in that they usuallyappeared while she was opera type singing ina choir at church. They were also occasionallyprovoked by some conditions of hyperventila-tion such as blowing to cool hot soup, orblowing the dust oV a table. This suggestedan underlying ischaemic pathophysiology andprompted us to investigate changes in brainvasculature and parenchyma. The short livedchoreiform movements were usually pre-ceded by a tingling sensation in her left hand,which occasionally extended to the left leg.

An EEG between ischaemic episodesdisclosed diVuse slow waves bilaterally overthe hemispheres; these slow waves increasedas build up with the appearance of deltawaves during hyperventilation. Magneticresonance imaging showed areas of highsignal intensity in both frontal subcorticalregions, suggestive of focal ischaemic lesions

(fig A and B). We determined the patientscerebral vascular reserve using technetium-99m-HMPAO brain SPECT with acetazola-mide challenge. This demonstrated a de-creased vascular reserve in both frontal andtemporal lobes, as well as in the basal ganglia.Magnetic resonance angiography and subse-quent four vessel angiography showed nearlycomplete obstruction of the terminal portionof each internal carotid artery and the outlineof a moyamoya network (fig C andD). Stagedencephaloduroarteriosynangiosis was per-formed on the left and right sides, 1 weekapart, resulting in an eventual amelioration ofthe patients involuntary movements.

Chorea is one of the rarer, althoughacknowledged, presenting features ofmoyamoya disease; chorea is usually observed

in children.3 4

It is suggested that about 6% ofpatients with moyamoya disease have chorea.5

Other types of involuntary movements havebeen described in patients with moyamoyadisease: Valsalva related seizures,6 recurrentepisodes of carpopedal spasm,7 recurrent tor-ticollis,8 and limb shaking transient ischaemicattack.9 Hemichorea is characterised by uni-lateral, brief, coarse, irregular, wavering,involuntary movements, and is usually causedby some asymmetric, focal brain lesion. Theclinical presentation of our patient was associ-ated with opera type singing.

Singing requires both hyperventilation andthe breath holding Valsalvas manoeuvre.Hyperventilation causes an increase in arte-rial oxygen tension, which subsequentlycauses vasoconstriction, which, in turn,

reduces blood flow. In addition, Valsalvasmanoeuvre increases cerebral venous pres-sure, which then increases intracranial bloodvolume and intracranial pressure, therebyreducing the arterial perfusion pressure.Thus, in those regions of the basal gangliaandcortexthat arealready critically perfused,hyperventilation and Valsalvas manoeuvrecan easily lead to transient ischaemic insult,which may be clinically manifested byinvoluntary movements. It seems likely thathyperventilation and breath holding actsynergistically to reduce brain perfusion. Inthis patient, the hemichoreic episodes wereattributed to hypoperfusion of the contralat-eral cerebral hemisphere, and not to epilep-

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togenic activity. Staged left and right en-cephaloduroarteriosynangiosis, using afrontal branch of the superficial temporalartery, was carried out, 1 week apart. Thisprocedure eventually ameliorated the pa-tients choreic movements.

Chorea is not unusual in moyamoyadisease. However, the causes of chorea aremanifold and careful neuroradiological andclinical evaluation is required to distinguishthem.10 Our findings emphasise thatmoyamoya disease should be included in thediVerential diagnosis of adult onset chorea.Recognition of this uncommon form ofocclusive carotid disease is important in theearly diagnosis and proper management of

neurological deficits.

This study was partly supported by a ClinicalResearch Fund from Chungbuk National Univer-sity Hospital.

S-H HANDepartment of Neurology,Chungbuk National

University Hospital, Chungbuk 361711,Korea

Y-G KIMDepartment of Neurosurgery

S-H CHADepartment of Radiology

S-Y CHUNG

Department of Pediatrics,Our Lady of Mercy

Hospital, Catholic University Medical College,

Inchon, Korea

Correspondence to: Professor Seol-Heui Han

[email protected]

1 Suzuki J, Kodama N. Moyamoya disease: areview. Stroke 1983;14:1049.

2 Bruno A, Adams HP Jr, Biller J, et al. Cerebralinfarction due to moyamoya disease in youngadults. Stroke 1988;19:82633.

3 Watanabe K, Negoro T, Maehara M, et al.Moyamoya disease presenting with chorea.Pediatr Neurol1990;6:402.

4 Levin SD, Hoare RD, Robinson RO. Childhoodmoyamoya presenting as dementia: report of acase. Dev Med Child Neurol 1983;25:7947.

5 Pavlakis SG, Schneider S, Black K, et al .Steroid-responsive chorea in moyamoya dis-ease. Move Disord1991;4:3479.

6 Robertson NP, Compston DAS, Kirkpatrick P.Moyamoya disease presenting as Valsalvarelated partial seizures. J Neurol Neurosurg Psy-chiatry 1999;66:111.

7 Chaudhuri KR, Edwards R, Scott J, et al. Adultmoyamoya disease. BMJ1993;307:8524.

8 Yasutomo K, Hashimoto T, Miyazaki M, et al.Recurrent torticollis as a presentation ofmoyamoya disease. J Child Neurol 1993;8:1878.

9 Ohkawa S, Tabuchi M, Yamadori A. A case ofmoyamoya-like disease with repetitive TIAon drinking. Rinsho Shinkeigaku 1992;32:75862.

10 Pelletier J, Cabanot C, Levrier O, et al. Angiod-ysplasia of moyamoya type disclosed by choreicinvoluntary abnormal movements during oralcontraception. Apropos of 2 cases. Rev Neurol(Paris) 1997;153:3937.

Late recurrence of glossopharyngeal

neuralgia after IXth and partial Xth

nerve rhizotomy: treatment by

microvascular decompression

Glossopharyngeal neuralgia, or vagoglos-sopharyngeal neuralgia as some would pre-fer,1 is a rare condition, occurring with a fre-quency of about 1% of that of trigeminalneuralgia. Medical treatment, particularlywith carbamazepine, is usually eVective. A

significant number of patients do, however,become refractory and go on to surgicaltreatment. The best established surgicaltreatment is rhizotomy of the glossopharyn-geal and upper vagal nerve roots, whichseems to be invariably eVective if the diagno-sis is correct although it is not withoutmorbidity and even mortality.2 Late recur-rence after such treatment, as describedbelow, has not previously been reported andraises interesting issues of mechanism andmethod of treatment which are considered inthis brief report.

The patient initially presented in 1988 as a23 year old woman with typical glossopharyn-geal neuralgia, experiencing severe intermit-tent pain in the left side of the throat, the backof the tongue, and the ear. The pain was

aggravated by talking and swallowing andrelieved, to some degree, by pressure on theleft side of the neck. At first there was a goodresponse to carbamazepine. When medicationwas stopped after several months the painreturned and was less well controlled with afurther course of the drug. Neurologicalexamination, CT, and MRI were normal. In1989 she underwent posterior fossa craniec-tomy and exploration of the IXth and Xthcranial nerve roots. No lesion, in particular novascular compression, was identified. The leftIXth nerve root and the two uppermost Xthnerve rootlets were divided adjacent to thebrain stem. Her postoperative course wasuncomplicated and she remained entirelysymptom free for over 9 years.

In 1998, now aged 33 years, she developed

recurrence of her original pain which shedescribed as essentially identical to that at theinitial presentation.Again the pain respondedto carbamazepine but required a high dose(1200 mg daily) which was accompanied bytroubling side eVects (drowsiness and dizzi-ness). In addition she was not completelypain free. Neurological examination and fur-ther MRI were normal. In October 1998 afurther posterior fossa exploration was car-ried out. The previously divided nerve rootswere identified and the completeness of theinitial section confirmed. There was now,however, a large, ectatic vertebral artery towhich the proximal ends of the previouslysectioned roots were adherent and which wasdistorting the remaining Xth nerve rootletsand the XIth nerve. A microvascular decom-

pression was carried out with a Teflon patchbeing placed between the ectatic artery andthe normal and previously sectioned nerveroots. The procedure was without complica-tion and the patient has remained well andentirely pain free since that time (18 months).

The first description of glossopharyngealneuralgia is credited to Weisenberg in 1910,in a patient in whom the pain was secondaryto a cerebellopontine angle tumour. The painis characteristic although two variants havebeen described; an otitic form with pain pre-dominantly deep in the ear, in the externalacoustic meatus, and the mastoid region andan oropharyngeal form in which the pain isexperienced in thepharynx, thetonsillar area,

(A and B) FLAIR axial images, showing bilateral focal ischaemic lesions in the frontal white matter.Low signal intensities surrounded by hyperintense rims are chronic lacunae (arrows) (C) Time of

flight MR angiography,indicating that both middle cerebral arteries were unidentifiable. Notemultiple tortuous flow signals, suggestive of moyamoya vessels (arrowheads). (D) Right internalcarotid angiogram, demonstrating middle cerebral artery occlusion, moyamoya vessels (curved

arrows), and the leptomeningeal collateral blood flow from the posterior circulation (straight arrows).

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the soft palate, and the posterior third of thetongue. For patients refractory to medicaltreatment several surgical options are avail-able including extracranial avulsion, intracra-nial preganglionic root section, trigeminaltractotomy, either open3 or percutaneous CTguided, and microvascular decompression.As mentioned at the outset, intracranial rootsection has been the most often employedand is generally regarded as curative. It was,however, realised early that section of theupper vagal rootlets is important in that somecases without the additional section wereeither not relieved or experienced earlyrecurrence.2 More recently microvasculardecompression has been employed, particu-larly by Jannetta et al, with complete relief ofpain in 76% and substantial improvement ina further 16% in the largest series, with amean follow up of 48 months.4 As withtrigeminal neuralgia, the actual incidence ofpresumed causative neurovascular conflictand, indeed, the exact mechanism of causa-tion are as yet unresolved questions.

The particular dilemma posed by thepresent case had both a diagnostic and atherapeutic arm, referable in each caseultimately to mechanism. The only reportedcases of recurrence after preganglionic sec-

tion are the small group, referred to above, inwhom only the IXth nerve root had been cutand who subsequently responded to sectionof the upper vagal rootlets and one patientwho had had both a IXth and partial Xthrhizotomy and who later responded to atrigeminal nerve procedure. In these casesfailure was typically either immediate or notlong delayed. In the largest series reportingthe results of treatment2 and in a smallerseries with long follow up5 there were norecurrences after preganglionic section of theIXth and upper Xth roots. Likewise, aftertotal sensory root section via the posteriorfossa (Dandy procedure) trigeminal neural-gia does not recur.

In our case, assuming completeness of theinitial section, there seemed to be, essentially,

three possible explanations for the recurrentpain. Firstly, that the pain was due to involve-ment of the remaining non-trigeminal so-matic aVerent components of the spinaltrigeminal nucleus (in the VIIth and theremainder of the Xth cranial nerves); sec-ondly, that it was some form of postdenerva-tion pain akin to the anaesthesia dolorosadescribed after Vth nerve section1 and in oneinstance afterIXth nerve section; and,thirdly,it was a form of trigeminal neuralgia, therebeing a reported coincidence of the twoforms of neuralgia in a few cases.2 The closesimilarity of the recurrent to the initial pain,both in nature and site, the long period sincethe initial pain, and the response to car-bamazepine all favoured the first possibility.On the basis of this diagnosis, coupled with

the patients relative youth and, it must besaid, her strong insistence, re-exploration wasundertaken as described above. Whateverones position on the vascular compressiontheory of thecause of cranial nerve neuralgiasthe findings were impressive and, in conjunc-tion with the undesirability of further nervesection, encouraged treatment by microvas-cular decompression alone. The immediacyof pain relief, sustained now for 18 months,supports this decision. It might be arguedthat the presumed vascular compression wasoverlooked at thefirst procedure butthereareseveral points against this. Firstly, bothprocedures were performed by the same sur-geon, experienced in posterior fossa surgery,

and the area of compression was in the sameplace as the initial section;. Secondly, theyoung age at first presentation is against avascular pathology, particularly where thevertebral artery is causative; and thirdly, thereis a reported incidence of new vascular com-pression in re-exploration for recurrenttrigeminal neuralgia.

In conclusion, the salient points to emergefrom this brief report are that vagoglossopha-ryngeal neuralgia can recur after IXth andpartial Xth nerve section and that this patientprovides evidence for a pure vagal neuralgia.This supposition is supported by the findingthat even the most caudal vagal rootlets maycarry general somatic aVerent fibres to thespinal trigeminal tract.1 In addition, the twoseparate episodes with diVering pathologiesraise the interesting question of whether thereis a particular propensity for neuralgia whichmay or may not require a vascular trigger.This bears on the point raised by Adams et alas to why there are so many possibly causativevessels and so few neuralgias.6

BKO and IJ are supported by the Sydney UniversityMedical Foundation Wood Grant and by theMadeline Foundation for Neurosurgical Research.

B K OWLER

Department of Neurosurgery,Royal Prince Alfred

Hospital Camperdown, NSW, 2050,AustraliaI JOHNSTON

Department of Surgery, University of Sydney,Sydney,

NSW, 2006, Australia

M KENNEDYDepartment of Medicine,Manly Hospital, Manly,

NSW 2095, Australia

Correspondence to: Dr I Johnston, GPO Box 811,Hobart, Tasmania 7001, [email protected]

1 White JC, Sweet WH. Pain and the neurosurgeon:a 40 year experience. Springfield, Illinois: CCThomas, 1969.

2 Rushton JG, Stevens C, Miller RH. Glossopha-ryngeal (vagoglossopharyngeal) neuralgia. Astudy of 217 cases. Arch Neurol 1981;38:2015.

3 Kunc Z. Treatment of essential neuralgia of the9th nerve by selective tractotomy. J

Neurosurg1965;23:494500.4 Resnick DK, Jannetta PJ, Bissonnette D, et al.Microvascular decompression for glosso-pharyngeal neuralgia. Neurosurgery 1995;36:649.

5 Taha JM, Tew JM. Long term results of surgicaltreatment of idiopathic neuralgias of theglossopharyngeal and vagal nerves. Neurosur-

gery 1995;36:92631.6 Adams CTB, Kaye AH, Teddy PJ. The treat-

ment of trigemina neuralgia by posterior fossamicrosurgery. J Neurol Neurosurg Psychiatry1982;45:10206.

Immunohistochemistry distinguishes

between Picks disease and cor ticobasal

degeneration

The clinical syndrome of frontotemporaldementia is associated with several neurode-

generative disorders: Picks disease, corticoba-sal degeneration, motor neuron disease-associated dementia (MND-dementia),frontotemporal dementia and parkinsonismlinked to chromosome 17 (FTDP-17), andfrontal lobe degeneration (FLD). Thesedisorders, although they do not match the fre-quency of Alzheimers disease, are far fromuncommon, and present clinicians and neu-ropathologists with formidable, if not insur-mountable diagnostic diYculties. However,recent advances in cellular and molecularpathology, biochemistry, and molecular ge-netics have been instrumental in their nosolo-gical definition. The discovery of a mutationin the tau protein gene on chromosome 17 in

1998 has established that several phenotypi-cally heterogeneous familial dementias with aconfusing variety of names all belong toFTDP-17.1 2 Most but not all frontotemporaldementias are characterised by intracellularinclusions formed by abnormal cytoskeletalcomponents, both in neurons and in glialcells. Picks disease, corticobasal degenera-tion,and FTDP-17 belongto the largergroupof tauopathies, as their hallmark lesionscontain tau protein, distinguishing them fromMND-dementia and FLD, two disorderswithout tau pathology. Of the three tauopa-thies, FTDP-17 can be defined by its geneticabnormality, whereas the diVerential diagno-sis of Picks disease and corticobasal degen-eration remains diYcult and controversial.

Clinically Picks disease is characterised byfrontal and anterior temporal lobe dysfunc-tion and progressive dementia, whereas neu-ropathologically the underlying frontotempo-ral atrophy is complemented histologically bythe presence of large, swollen, achromaticneurons, the Pick cells, and by tau positiveintraneuronal inclusions, the Pick bodies. Theclinical features of corticobasal degenerationinclude asymmetric extrapyramidal signs,parkinsonism, and the alien limb phenom-enon (apparent purposeful movements which

are not under voluntary control) followed bycognitive impairment. Histologically there isneuronal loss, astrocytosis, and tau positiveneuronal and glial inclusions, but the mostprominent feature is the presence of large,swollen neurons, morphologically indistin-guishable from Pick cells. It is the occurrenceof these cells in both disorders which causesmost of the diVerential diagnostic problems.

In the human central CNS six tau isoformsare generated by alternative splicing andthese are then postranslationally phosphor-ylated. At molecular level the electrophoreticprofiles of aggregated tau proteins in theseneurodegenerative disorders are disease spe-cific. For example, although both Picksdisease and corticobasal degeneration aretauopathies, characterised by tau positive cel-

lular inclusions, their tau profile is apparentlydiVerent: the tau doublet is 64 and 69 kDa incorticobasal degeneration, but55 and64 kDain Picks disease.3 Here we report the use oftau antibodies which, exploiting the diVerentphosphorylation patterns of these two disor-ders, has made a more accurate neuropatho-logical diagnosis possible.

Sections from the frontal lobe and the tem-poral lobe (including the hippocampus) from10 cases of corticobasal degeneration and 10cases of Picks disease were examined byimmunohistochemistry, using phosphoryla-tion independent (SMI51, TP007, TP70,304, 189) and phosphorylation dependent(AT180, AT270, AT8, 12E8) anti-tau anti-bodies. All sections were immunostainedaccording to a standardised protocol using

the avidin-biotin complex (DAKO) withappropriate positive and negative controls.All the swollen neurons and neuronal andglial inclusions were positively immunos-tained with all the anti-tau antibodies in cor-ticobasal degeneration. However, in Picksdisease all the antibodies but one immunos-tained the Pick bodies and the large swollenPick cells: antibody 12E8 gave negativeresults (figure A and B).

Phosphorylation at the site of Ser262/Ser356 is thought to be one of the mostprominent factors aVecting the biologicalactivity of tau.3 In corticobasal degenerationantibody 12E8 detected the phosphorylatedepitopes Ser262 and/or Ser356, whereas in


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Picks disease these sites remain unphospho-rylated and consequently this antibody didnot label any of the Pick bodies or Pick cells. 4

These findings are important both from apractical and from a theoretical point of view.The immediate practical implication is amore accurate neuropathological diagnosis,enabling Picks disease to be distinguished

from corticobasal degeneration; this, in turn,is essential for improving clinical investiga-tions. In addition, new insights into themolecular pathology of these disorders con-tribute to the nosological definition and bet-ter understanding of a complex group ofneurodegenerative diseases.

K BELLN J CAIRNS

P L LANTOS

Institute of Psychiatry, Kings College London,

Department of Neuropathology, Denmark Hill, London

SE5 8AF, UK

M N ROSSOR

Institute of Neurology, University College London,

Department of Clinical Neurology,Queen Square,

London WC1N 3BG, UK

Correspondence to: Dr PL Lantos

[email protected]

1 Lantos PL. Cracking an enigma: the puzzle ofunusual dementias. In: Iqbal K, Swaab DF,Winblad B, et al, eds. Alzheimers disease andrelated disorders. Chichester: John Wiley,1999:50922.

2 Spillantini MG, Goedert M. Tau mutations infamilial frontotemporal dementia. Brai n2000,123:8579.

3 Haque N, Tanaka T,Iqbal K, et al. Regulation ofexpression, phosphorylation and biologicalactivity of tau during diVerentiation in SY5Ycells. Brain Res 1999;838:6977.

4 Delacourte A, Sergeant N, Wattez A, et al. Vul-nerable neuronal subsets in Alzheimers andPicks disease are distinguished by their tauisoform distribution and phosphorylation. Ann

Neurol1998;43:193204.

CORRESPONDENCE

Neurological emergencies: acute stroke

We greatly enjoyed reading the recently pub-lished review on acute stroke by Davenportand Dennis.1 Their didactic approach andstrict compromise to distinguishing betweenevidence basedapproachesand their personalbeliefs deserve compliment. We would like tocontribute by clarifying some information ontwo topics.

Firstly, the authors make a brief commenton the use of anticoagulants in the treatment

of cerebral venous thrombosis (CVT) indi-

cating that a recent randomised trial showeda non-significant favourable eVect.2 This may

lead to a misinterpretation. Most expertscurrently agree that anticoagulation should

be used in the acute treatment of CVT based

on the available evidence. In 1991, Einhaulpet al3 published the results of their ran-

domised double blind prospective study

comparing heparin and placebo. This studywas prematurely interrupted after enrolling20 patients because of the dramatic diVer-ences noted in outcome in favour of theheparin group (basically eight patients recov-ered fully and no deaths occurred in theheparin arm whereas only one patient recov-ered completely and three others died in theplacebo group). Concerns about possiblemethodological flaws in this German trialfueled some controversy about its results.This led to a new trial by the Cerebral VenousSinus Study Group3 which randomised 60patients with CVT to receive nadroparin orplacebo for 3 weeks. Poor outcome wasdefined as death,Barthel index of less than 15at 3 weeks or Oxford handicap score equal orgreater than 3 at 12 weeks. The resultsshowed poor outcome in six of 30 patients(20%) in the nadroparin arm and seven of 29(24%) in the placebo group at 3 weeks andfour of 30 (13%) in the nadroparin treatedpatients versus six of 29 (21%) in the placebogroup (absolute risk reduction of 7% andrelative risk reduction of 38% for a non-statistically significant diVerence). But alsovery remarkably, there were no new sympto-matic cerebral haemorrhages even among the15 patients treated with anticoagulation whohad haemorrhagic lesions on the initial CT.Finally, the same authors performed a meta-analysis combining the results of the two

available trials

2 3

which showed a modest butclinically important (although not statisti-cally significant) benefit in the use of antico-agulation (absolute risk reduction of 14% inmortality and 15% in death or dependency,with relative risk reductions of 70% and 56%respectively). When combined with theproved safety of anticoagulation even in thesetting of pre-existent haemorrhagic infarctand the highly unpredictable course ofpatients with CVT, these results shouldencourage the use of anticoagulation in thetreatment of CVT.

Secondly, Davenport and Dennis men-tioned the use of decompressive craniectomyas one of the interventions that may be used

in patients with stroke who are rapidlydeteriorating from raised intracranial pres-sure. However, they questioned whether thisaggressive approach was associated withimproved survival with acceptable quality oflife.1 Growing experience with our patientsas well as the available literature seems toindicate that it does, especially when decom-pressive surgery is performed early. Schwab etal4 studied 63 patients with complete middlecerebral artery (MCA) infarctions and evi-dence of increased intracranial pressuretreated with either early (within 24 hours ofsymptom onset) or late craniectomy. Mor-tality was 27% (compared with 78% inhistorical controls) and all suvivors werereported to be able to walk short distanceswithout assistance and none were left withglobal aphasia. Mean Barthel index scoreswere 68.8 in the early hemicraniectomygroup, 62.6 in the late hemicraniectomygroup, and 60 in historical controls (but thevery high mortality in this last group mayaccount for a less dramatic diVerence infunctional outcome). Similar favourable re-sults were reported by Carter et al5 in their aretrospective analysis of 14 patients treatedwith decompressive surgery after massivenon-dominant hemispheric infarctions. Eightof their 11 surviving patients were able to

function with minimal to moderate assistance(Barthel index >60) 1 year after the surgery.Depression and failure to reintegrate sociallywere often found in this group of patients 5 asopposed to the experience reported bySchwab et al.4

In conclusion, decompressive craniectomyseems a valuable treatment option in cases ofmalignant MCA infarction, especially wheninvolving the non-dominant hemisphere.This surgery is potentially lifesaving andreported functional outcomes are encourag-ing.Therefore,it needs to be considered earlyin every patient with complete MCA strokesshowing incipient signs of increased intracra-nial pressure.

A RABINSTEIN

Department of Neurology,University of Miami School

of Medicine,1501 NW 9 Avenue, Miami, FL 33136,

USA

1 Davenport R, Dennis M. Neurological emer-gencies: acute stroke. J Neurol NeurosurgPsychiatry 2000;68:27788.

2 Einhaupl KM, Villringer A, Meister W, et al.Heparin treatment in sinus venous thrombosis.Lancet1991;338:597600.

3 De Brujin SFTM, Stam J, for the CerebralVenous Sinus Thrombosis Group. Randomisedplacebo controlled tr ial of anticoagulant treat-ment with low molecular weight heparin for cer-ebral sinus thrombosis. Stroke 1999;30:4848.

4 Schwab S, Steiner T, AschoV A, et al. Earlyhemicraniectomy in patients with completemiddle cerebral artery infarction. Stroke 1998;29:188893.

5 Carter BS, Ogilvy CS, Candia GJ, e t a l .One-year outcome after decompressive surgeryfor massive nondominant hemispheric infarc-tion. Neurosurgery 1997;40:116875.

Davenport and Dennis reply:

We are grateful for Rabinsteins interest andcomments. Although our interpretation ofthe available data may be more conservative,we do indeed consider anticoagulation forCVT, but do not think that it is appropriate inall cases. Similarly, we have consideredcraniectomy for malignant MCA occlu-sion, but so far we have not thought it appro-priate to proceed. We note the good out-comes from the published case series andawait the results of randomised trials withinterest. However, many of the case serieshave involved rather younger than average

Positive and negative immunostaining in large, swollen neurons by anti-tau antibody 12E8 incorticobasal degeneration (A) and in Picks disease (B), respectively. ABC method (DAKO).


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patients, who have a greater capacity forfunctional recovery than older people (whomake up the bulk of our case load), in whomwe doubt whether such good functional out-comes are achievable.

R J DAVENPORTM S DENNIS

Department of Clinical Neurosciences, Western General

Hospital, Crewe Road,Edinburgh EH4 2XU,

Scotland,UK

Correspondence to: Dr R J [email protected]

Illusory movements of the paralysed

upper limb in stroke

Feinberg et al have recently reported theassociation between anosognosia for hemi-plegia and the illusion of movement of theparalysed upper limb.1 They considered theillusion a form of confabulation that isdistinct from other phantom phenomena.This explanation is not supported by myfindings in a patient with a stroke who expe-rienced transient purposeful movements ofhis paretic hand.

The patient was a 66 year old right handedman who presented with acute onset weak-ness of his right arm and leg and slurring of

his speech. He was known to be hypertensiveand a non-insulin dependent diabetic patient.Neurological examination confirmed thepresence of right hemiplegia with facialinvolvement and mild to moderately severedysphasia. Muscle power, as measured by theMedical Research Council (MRC) scale, was1/5 and 2/5 in the upper and lower limbsrespectively. Spinothalamic and posteriorcolumn sensations were intact. No visualfielddefects were found on examination using theconfrontation method. There was no aster-eognosis or sensory extinction of tactile orvisual stimuli. The patient was alert andcooperative. His comprehension of spokenand written language was good but there wasevidence of moderately severe nominal dys-phasia. The rest of the physical examination

was normal. Brain CT confirmed the pres-ence of a non-haemorrhagic infarct in the leftcorona radiata. The patient scored 19 on themini mental state examination. There was noevidence of hemineglect as assessed clinicallyand with the line bisection test. The patientwas correct in 8/10 items of the anosognosiafor hemiplegia questionnaire.1

Six weeks after his stroke the patient devel-oped an itchy skin condition, probably a drughypersensitivity reaction. When he scratchedhis skinwithhis left(good) handto relieve theitching he thought that his right hand wasalso simultaneously scratching the same skinarea. The right hand stopped workingwhen he ceased scratching his skin but theperception of movement recurred each timehe scratched the same or a diVerent skin area

until his symptoms resolved 2 weeks later.The use of the left hand for other activitiesdid not result in a similar phenomenon. Thepatient had good insight into his motor func-tional disability and described his perceivedhand movements as a silly situation.

The case reported here demonstrates thatillusory movements in stroke are independentof anosognosia for hemiplegia. This finding isin agreement with those of a previous study. 2

It also suggests that illusory movements areunlikely to be the product of confabulations.Confabulation is primarily a memory disor-der and results from lesions in the forebrainand medial temporal lobe that disruptconnections of the limbic system.3 The

patient reported here did not have an amnes-tic syndrome; neither was his brain lesion (asdemonstrated with CT) in the limbic systemarea. It seems likely that the illusory move-ments described by Feinberg et alwere phan-tom phenomena associated with reorganisa-tion of cortical maps and neural plasticity.4

A M O BAKHEIT

University of Plymouth,Mount Gould Hospital,

Plymouth PL4 7QD, UK

1 Feinberg TE, Roane DM, Ali J. Illusory limbmovements in anosognosia for hemiplegia. JNeurol Neurosurg Psychiatry 2000;68:51113.

2 Lu LH, Barrett AM, Schwartz RL, et al .Anosognosia and confabulation during theWada test. Neurology 1997;49:131622.

3 Hashimoto R, Tanaka Y, Nakano I. Amnesicconfabulatory syndrome after focal basal fore-brain damage. Neurology 2000;54:97880.

4 Ramachandran VS, Hirstein W. The perceptionof phantom limbs. The DO Hebb lecture.Brain 1998;121:160330.

Feinberg and Roane reply:

The patient described by Bakheit is of interestbut is not relevant to our investigation.1 To beincluded in our investigation, patients wererequired to have righthemispheric strokes andlefthemiplegia.Furthermore, 10/11 patients inour study had left hemispatial neglect and left

hemisensory defect. The patient described byBakheit had a right hemiplegia, and had noneglect or sensory defects. Therefore, Ba-kheits patient would not have qualified for ourstudy and cannot be fairly compared with ourstudy population. Additionally, the factitiousmovements described in Bakheits patient dif-fered from those experienced by our patientsin two significant respects. Firstly, Bakheitspatient experienced a mirroring phantommovement of the plegic right limb only whenthe normal hand was active. In our study, tominimise the potentially confounding role ofcompletion, we specifically excluded from themain analysis those patients who only experi-enced illusory limb movements when the non-plegic limb was active. Secondly, the phantommovements experienced by Bakheits patient

were restricted to a particular idiosyncraticactionnamely, scratchingas opposed toour patients who experienced illusory limbmovements when simply asked to raise the leftarm, an action which apparently failed to elicitfactitious movement in Bakheits patient.Therefore, according to the criteria set out inour investigation, the movements experiencedby the patient of Bakheit would not be catago-rised as illusory limb movements in our study.Finally, it should be further noted that ourpatients were examined within a week of onset(some within a day) of acute hemiplegia,before significant reorganisation of corticalmaps and neural plasticity is likely to haveoccurred. The patient of Bakheit is reported tohave had phantom movements at 6 weeks afteronset of hemiplegia when cortical reorganisa-

tion andneuralplastic eV

ects are more likelytohave occurred.In our opinion, Bakheit has committed the

same error that we have previously cautionedagainst.2 3 He has failed to distinguish phan-tom limb movements in his patient fromillusory limb movements that occur in associ-ation with right hemispheric damage andhemineglect. Patients with true phantomlimbs, as in Bakheits case, do not deny theidentity of the actual arm and recognise thephantom movements as illusory. By contrast,the patients with illusory limb movements inour study all denied ownership of the plegicarm and believed in the reality of thefactitious movements. It is in this group in

which we found illusory limb movements andwhich bears a relation to anosognosia andrepresents a variety of confabulation. Finally,we point out that confabulation is notconfined to amnestic patients, and occurs inother conditions such as Antons syndrome.

TODD E FEINBERG

Yarmon Neurobehavior and Alzheimers Disease

Center,Beth Israel Medical Center, 317 East 17th

Street, New York, New York 10003,USA

DAVID M ROANE

Department of Psychiatry, Beth Israel Medical Center,16th Street and 1st Avenue, New York, New York

10003,USA

Correspondence to: Dr Todd E Feinberg

1 Feinberg TE, Roane DM, Ali J. Illusory limbmovements in anosognosia for hemiplegia. J

Neurol Neurosurg Psychiatry 2000;68:51113.2 Feinberg TE. Anosognosia and confabulation.

In: Feinberg TE, Farah M, eds. Behavioral neu-rology and neuropsychology. New York:McGraw-Hill, 1997:36990.

3 Feinberg TE, Roane DM. Anosognosia, com-pletion, and confabulation: the neutral-personal dichotomy. Neurocase 1997;3:7385.

Social deprivation and prevalence of

epilepsy and associated health usage

I read the study of Morgan et al on social

deprivation and prevalence of epilepsy andassociated health usage1 with great interestand would like to add some remarks from myexperience in the most impoverished regionof the United States, near the MississippiDelta. I would caution that it is especially in apoor and traumatised population, extremelydiYcult to diVerentiate between true electri-cal events and non-epileptic (or pseudo) sei-zures.2 We have known since Charcot aboutthe correlation between psychological trau-matic states, to which poverty is intimatelyrelated and conducive, and hystericalseizures.35 There is a substantial comorbidityof epileptic and non-epileptic seizures.2 Infact, what I see here in Mississippi is moreoften than not a mixture of both and withoutproper, expensive testing, such as video EEG,

it is sometimes impossible to make the diV

er-ence. Because of the way the data werecollected, it is diYcult to know from thepaper of Morgan et al1 whether pseudosei-zures were properly taken into account whenassessing the prevalence of epilepsy. Thesame caveat applies to the ascertainment ofpsychiatric comorbidity. A thorough neu-ropsychiatric screening of the clientele of anepilepsy clinic would disclose a much higherpsychiatric comorbidity than the record link-age used here. Because of the way neurolo-gists are trained, at least in the United States,most psychiatric comorbidity in neurologypatients in general probably goes undiag-nosed.

What the usage data of Morgan et al doshow is how vain the treatment of neurologi-

cal illness remains without addressing itssocial ecology. This certainly is true in Walesas well as in Mississippi.

M PRETERDepartments of Psychiatry and Neurology, University

of Mississippi Medical Center, 713 Northwest Avenue,

Durant,MS 390633007, USA

Correspondence to:[email protected]

1 Morgan CLI, Ahmed Z, Kerr MP. Social depri-vation and prevalence of epilepsy and associ-ated health usage.J Neurol Neurosurg Psychiatry2000;69:1317.

2 Devinsky O. Non-epileptic psychogenicseizures: quagmires of pathophysiology, diag-nosis, and treatment. Epilepsia 1998;39:45862.


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3 Bowman ES, Markand ON. The contribution oflife events to pseudoseizure occurrence inadults. Bull Menninger Clin 1999;63:7088.

4 Bowman ES, Markand ON. Psychodynamicsand psychiatric diagnoses of pseudoseizuresubjects. Am J Psychiatry 1996;153:5763.

5 Cartmill A, Betts T. Seizure behaviour in apatient with post-traumatic stress disorder fol-lowing rape. Notes on the aetiology of pseudo-seizures. Seizure 1992;1:336.

The authors reply:

We thank Preter for his interest in our paper

and for his comments identifying the prob-lems associated with correctly diagnosingepilepsy. As we have indicated in the paper,these problems are intensified by record link-age techniques with the possibility of bothfalse positive and false negative results. Wediscussed in some detail the issue of falsenegatives as we think this to be the greaterproblem within our study and so Preterscomments about false positives, particularlypseudoseizures, are most useful. Patients withpseudoseizures, however, will still place ademand on epilepsy services and thereforeremain an issue in the allocation of resourceswithin areas of high social deprivation.

We also accept that our ascertainment ofpsychiatric morbidity will be skewed towardsthe more severe forms of psychiatric comor-

bidity as, by our methodology, they will haveto have come into contact with secondarycare services. It is, however, these patients,excluded from our second analysis, who willhave the greatest influence upon social andmaterial deprivation.

We think, however, that despite these cave-ats, the findings of the study remain valid. Asis often the case, a record linkage study raisesas many questions as it answers and moredetailed research is required in this area.

C L MORGANZ AHMEDM P KERR

Department of Psychological Medicine, University of

Wales, College of Medicine,Heath Park, CardiV

CF4 4XW, UK

Correspondence to: Dr M P [email protected]

Neuropsychological abnormalities in

first degree relatives of patients with

familial Parkinsons disease

We enjoyed reading the paper by Dujardin etal1 who investigated possible preclinicalfeatures of asymptomatic relatives in familieswith Parkinsons disease. A battery of neuro-psychological tests disclosed impaired frontalexecutive function in 15 of 41 first degreerelatives of patients with familial Parkinsonsdisease. Nine showed general frontal execu-tive impairment. The other six only had lowerscores in parts of motor dynamic sequences

and word fluency. The authors concludedthat this dysexecutive syndrome could be apremorbid expression of Parkinsons disease.It could represent an early nigrostriataldysfunction in first degree relatives ofprobands with familial Parkinsons diseasewho may thus carry a higher genetic risk ofdeveloping the disease.

Dujardin et aldescribe modifications of thecognitive status which we reported in unaf-fected co-twins of patients with Parkinsonsdisease2 After this, 3 years ago our grouppublished a similar study3 to the one byDujardin et al. As they do not mention ourfindings, we briefly discuss our data inrelation to their results. We compared 35

motor asymptomatic first degree relatives(mean age 52.6 (SD 10.6) years) of familieswith at least two members aVected byParkinsons disease to 29 relatives (mean age52.1 (SD 4.1) years) of patients with sporadicParkinsons disease and to 32 healthy con-trols (mean age 51.9 (SD 4.6) years). Toaccount for a possible low dopamine syn-drome, we studied memory, frontal lobefunction, mood, personality traits, somaticcomplaints, and fine motor abilities. Testsused were the short form of the Wechsleradult intelligence scale, the auditory verballearning test, the controlled oral word associ-ation test, the Wisconsin card sorting test(Nelson version), the paranoid depressionscale, the revised version of the Freiburg per-sonality inventory, a list of complaints, and astandardised finger tapping test. We foundthat first degree relatives of both patients withfamilial Parkinsons disease and those withsporadic Parkinsons disease diVered signifi-cantlyfrom controls in several tests.They hadlower scores in total fluency and fewercategories in the Wisconsin card sorting test.Relatives of both patients with familialParkinsons disease and with sporadic diseaseexpressed more impulsiveness, more strain,and less extraversion on personality assess-ment. In addition, relatives of patients with

familial Parkinsons disease had more errorsthan controls in the Wisconsin card sortingtest. Relatives of patients with sporadicParkinsons disease showed more depression,more somatic complaints, and inhibitednessthan controls and also less extraversion, lessemotionality, and a lower tapping rate of theright hand. Our results, both motor and non-motor, were comparable with those ofpatients with early stage Parkinsons diseaseand are in keeping with some of the findingsof Dujardin et al.

On average, our proband sample was 14years older than that of Dujardin et al, and bycontrast with these authors, we includedassessment of depression as a possibleconfounder of the neuropsychological testresults. Depression may have a substantial

impact on cognitive function,4 and a historyof depression is thought to be a risk factor fordeveloping Parkinsons disease.5 In our study,there were no correlations between cognitiveimpairment and depression. We thereforeconsidered frontal lobe dysfunction anddepression as independent signs of the lowdopamine syndrome in our samples. An-other important result of our investigationwas that, apart from one personality trait(aggressiveness), we could not establishdiVerences between relatives of patients withfamilial Parkinsons disease and those ofpatients with sporadic Parkinsons disease inany test item, nor were there item clusters insubsets of probands. Thus, according to ourdata, frontal lobe dysfunction and depressioncan be found to a variable degree in some

relatives of patients with both the familial andthe sporadic form of Parkinsons disease. Itshould be kept in mind that the finding ofsuch neuropsychological abnormalities doesnot prove that their origin is genetic.

B KISI HEBERLEIN

J HAGENAHH JACOBS

C KLEINP VIEREGGE

Department of Neurology,Medical University of

Lbeck,Ratzeburger Allee 160, 23538 Lbeck,

Germany

Correspondence to: Professor P [email protected]

1 Dujardin K, Duhamel A, Becquet E, et al.Neuropsychological abnormalities in fir st de-gree relatives of patients with familial Parkin-sons disease. J Neurol Neurosurg Psychiatry1999;67:3238.

2 HolthoV VA, Vieregge P, Kessler J, et al. Discord-ant twins with Parkinsons disease: positron emis-sion tomography and early signs of impairedcognitive circuits. Ann Neurol 1994;36:17682.

3 Vieregge P, Heberlein I, Kmpf D. Are neuro-psychological tests useful in screening for thegenetic risk of Parkinsons disease? Parkinson-ism and Related Disorders 1997;3:14150.

4 Channon S, Green PSS. Executive function indepression: the role of performance strategies in

aiding depressed and non-depressed participants.J Neurol Neurosurg Psychiatry 1999;66:16271.

5 Taylor CA, Saint-Hilaire MH, Cupples LA, etal. Environmental, medical, and family historyrisk factors for Parkinsons disease: a NewEngland-based case control study. Am J MedGenet1999;88:7429.

BOOK REVIEW

Juvenile Myoclonic Epilepsy: the Janz

Syndrome. Edited by B SCHMITZ and T

SANDER. (Pp 207, 42.50). Petersfield:

Wrightson Biomedical, 2000. ISBN 1871816 42 4.

Have you ever had that feeling that something

is just on the tip of your tongue but you cantquite get at it or that if only you had one morepiece of the jigsaw, you would be able to see thewhole picture? Welcome to juvenile myoclonic

epilepsy. It is one of the most rewarding condi-tions in epilepsy to diagnose and treat. Indeedjuvenile myoclonic epilepsy has the unusual,dual virtues of being both common and

treatable. But what is it? This book introducesthe conditionprevalence 3%-11% of allepilepsy, easily diagnosed if you think to ask forearly morning twitchiness or clumsiness, char-acteristic EEG appearance etc. But then come

all the tantalising clues that leave one on the

brink of understanding. It is obviously geneticand a linkage to chromosome 6 has beensuggested for years, now honed down to near

the HLAgene. Buta recent analysis has tried tosubdivide juvenile myoclonic epilepsy accord-ing to electroclinical criteria to obtain morehomogeneous groups for genetic analysis and

this has suggested genetic heterogeneity. Whyare there so many focal elements in this gener-alised epilepsy syndrome? These include focalclinical seizure manifestations, focal EEG

changes, focal imaging changes such as thick-ening of the grey matter detectable by math-ematical techniques. What is the overlap withother syndromes such as childhood absence

epilepsy and why are seizures triggered byreading or praxis in some cases?

At least all can agree that it usually gets

better with valproate but comes back if youstop the drug. Unfortunately this text doesnot discuss other newer medications. Experi-ence with them is largely anecdotalexceptthetreatment of the myoclonus with benzodi-azepines and piracetam.

This book summarises our knowledge ofjuvenile myoclonic epilepsy in a readable andconcise but comprehensive text. The troubleis that we are on a threshold betweendescriptive knowledge and understanding sojuvenile myoclonic epilepsy remains onejigsaw piece short of a picture. It will be ofinterest primarily to those in the epilepsy andgenetics fields.

MARK MANFORD


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doi: 10.1136/jnnp.69.6.832

2000 69: 832-833J Neurol Neurosurg PsychiatryD DO, V L SHEEN and E BROMFIELDwith labetalolTreatment of paroxysmal sympathetic storm

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