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on both sides involving the vestibulospinaltracts bilaterally (figure C). Patients 2 and 3also had high intensity areas in the sameareas. Apart from lesions in this area, allshowed high signal intensity areas in the cer-ebral white matter.

This preliminary study shows that latenciesof a vestibulospinal reflex can be prolonged inmultiple sclerosis. As in these three patientsthe VEMPs were remarkably delayed ratherthan simply abolished as occurs in patientswith peripheral vestibular lesions,24 theVEMP delay could be attributed to demyeli-nation either of primary aVerent axons at theroot entry zone or secondary vestibulospinaltract axons rather than to lesions involvingvestibular nucleus neurons. The MRI find-ings in these patients were not inconsistentwith this proposition. Measurement ofVEMPs could be a useful clinical test toevaluate function of the vestibulospinal path-way and for detecting subclinical vestibulos-pinal lesions in suspected multiple sclerosis.

This study was supported by a Research Grant fromthe Intractable Diseases Fund (Vestibular Disor-ders) of the Ministry of Health and Welfare, Japan(1999).

KEN SHIMIZUTOSHIHISA MUROFUSHI

Neuro-otology Clinic, Department of Otolar yngology,Faculty of Medicine, University of Tokyo,

731 Hongo, Tokyo 1138655, Japan

MASAKI SAKURAIDepartment of Physiology, Teikyo University School of

Medicine, Tokyo,Japan

MICHAEL HALMAGYI

Neurology Department, Royal Prince Alfred Hospital,

Sydney, Australia

Correspondence to: Dr Toshihisa Murofushitoshi-tky@umin.ac.jp

1 Colebatch JG, Halmagyi GM, Skuse NF.Myogenic potentials generated by a click-evoked vestibulocollicreflex. J Neurol NeurosurgPsychiatry1994;57:1907.

2 Murofushi T, Matsuzaki M, Mizuno M. Ves-tibular evoked myogenic potentials in patientswith acoustic neuromas.Arch Otolaryngol Head

Neck Surg1998;124:50912.3 Murofushi T, Halmagyi GM, Yavor RA, et al.Vestibular evoked myogenic potentials in ves-tibular neurolabyrinthitis; an indicator of infe-rior vestibular nerve involvement? ArchOtolaryngol Head Neck Surg1996;122:8458.

4 Heide G, Freitag S, Wollenberg I, et al. Clickevoked myogenic potentials in the diVerentialdiagnosis of acute vertigo. J Neurol NeurosurgPsychiatry1999;66:787790.

5 Murofushi T, Curthoys IS. Physiological andanatomical study of click-sensitive primary ves-tibular aVerents in the guinea pig. ActaOtolaryngol (Stockh)1997;117:6672.

6 Kushiro K, Zakir M, Ogawa Y, et al. Saccularand utricular inputs to sternocleidomastoidmotoneurons of decerebrate cat. Exp Brain Res1999;126:41016.

7 Poser CM, Paty DW, Scheinberg L, et al. Newdiagnostic criteria for multiple sclerosis: guide-lines for research protocols. Ann Neurol1983;13:22731.

Sensory ataxia as the initial clinical

symptom in X-linked recessive

bulbospinal neuronopathy

X-Linked recessive bulbospinal neuronopa-thy (X-BSNP) has previously been describedas a disease in which the first clinicalsymptoms which occur concern the motorsystem. A weakness of theshoulderand pelvicgirdle muscles as well as cramps and musclepain in the proximal limbs are normallyfound in the early stages.13 The onset ofX-BSNPgenerally rangesbetween the ages of25 and 50 years; the disorder then shows aslow but continuous progression of

symptoms.1 3 An involvement of facial andbulbar musculature with fasciculations andatrophy of these muscles and, therefore, oftendysarthria anddysphagia, arecommonsymp-toms of an advanced stage.1 3 Nevertheless,life expectancy does not seem to be consider-ably reduced.1 Sensory impairment wasreported to be minimal or non-existent.13

Pathoanatomical studies showed that adegeneration of both the lower motor andprimary sensory neurons represent the un-derlying pathological process for the clinicalsymptoms.4 The pathogenetic link betweenthe abnormally expanded CAG trinucleotiderepeat in the first exon of the androgenreceptor gene which is found in aVectedpatients and the depletion of the anteriorhorn cells and the primary sensory neuronswith consecutive axonal degeneration of thedorsal root fibres has not been establishedyet.4 5 Although central and peripheral sen-sory conduction has been shown to be highlyabnormal with absent or markedly prolongedsensory action potentials, most of the timethe clinical findings of only a little sensoryimpairment do not correspond well to thiselectrophysiological constellation.1 3 We re-port sensory ataxia as the initial clinicalsymptom in a patient with X-BSNP.

A 63 year old retired journalist felt likewalking on pillows for the first time whenhe was 45 years old. During the subsequentyears the distally accentuated and symmetricloss of sensibility for touch, temperature,pain, position, and vibration was progressivein the legsand lateralso in the arms. Atthe age of 48 he noticed fasciculations of thefacial muscles and a slow development of apainless, bilateral weakness of the proximalmuscles of the lower and upper limbs. Norelated disease was found in his fathers fam-ily; nothing is known about the maternal sideof his family history.

The clinical examination of the patientshowed a severe sensory gait ataxia as well as adyspraxia of his hands.Othersymptoms were atremor of the hands and occasional spasms of

the oral and pharyngeal musculature. Thefunctions of other cranial nerves were normal.Spontaneous fasciculations of the buccal mus-cles and less often of the proximal and distallimb musculature were seen. Deep tendonreflexes could generally not be detected andthere were no pathological reflexes. A proxi-mally accentuated weakness and amyotrophyof the legs and arms as well as a distally accen-tuated hypaesthesia for all qualities was found.There were no cognitive deficits, cerebellarataxia, or gynaecomastia.

Laboratory results were not abnormal(including plasmatestosterone, follicle stimu-lating hormone, luteinising hormone, andglucose tolerance) except for a raised creatinekinase (354 U/l). The CSF examination alsoshowed no abnormalities. Motor nerve con-

duction velocities were only slightly reducedwhereas sensory action potentials were ab-sent. Electromyography showed the typicalfeatures of chronic denervation in the proxi-mal muscles of the lower and upper limbs aswell as in the tongue. Motor evoked poten-tials showed normal central conduction timesbut partially prolonged latencies with stimu-lation of the cervical and lumbal roots. Withtibial and median nerve stimulation no soma-tosensory evoked potentials were foundneither at the cervical or lumbal nor at thecortical recording sites. Brain MRI wasnormal.The genetic analysis showed42 CAGtrinucleotide repeats within the androgenreceptor gene (normal length 1134 repeats),

which is a valuable criterion in the diagnosisof X-BSNP.5

The example of our patient shows that theelectrophysiological findings of the sensorysystem may correspond well to the clinicalsyndrome in X-BSNP. It is not clear whypatients with X-BSNP in most cases do notshow significant sensory impairment al-though substantial loss of the primarysensory neuron has been proved. We hopethat findings as in this case report may be anincentive for us to work for a betterunderstanding of the problem as to why aspecific neuronal degeneration can lead to aless specific pattern of clinical symptoms.

ANSGAR BUECKINGROBERT PFISTER

Department of Neurology, Zentralklinikum Augsburg,

Stenglinstrasse 2, D-86156 Augsburg, Germany

Correspondence to: Dr Robert Pfister

1 Harding AE, Thomas PK, Baraitser M, et al.X-linked recessive bulbospinal neuronopathy: areportof 10 cases.J Neurol Neurosurg Psychiatry1982;45:101219.

2 Kennedy WR, Alter M, Sung JH. Progressiveproximal spinal and bulbar muscular atrophyof late onset. A sex-linked recessive trait.

Neurology (Minneapolis)1968;18:67180.3 Wilde J, Moss T, Thrush D. X-linked bulbo-

spinal neuronopathy: a family study of three

patients.J Neurol Neurosurg Psychiatry1987;50:27984.4 Sobue G, Hashizume Y, Mukai E, et al. X-linked

recessive bulbospinal neuronopathy. A clinico-pathological study.Brain1989;112:20932.

5 La Spada AR, Paulson HL, Fischbeck KH. Tri-nucleotide repeat expansion in neurologicaldisease.Ann Neurol1994;36:81422.

Neuroleptic malignant syndrome

without fever: a report of three cases

Although fever is considered to be a cardinalfeature of neuroleptic malignant syndrome,we report on three patients who were afebrilebut had all the other features of the neurolep-tic malignant syndrome. This paper high-lights the need to suspect neuroleptic malig-nant syndrome and immediately initiate

investigation and appropriate management inany patient who develops rigidity and cloud-ing of consciousness while receiving antipsy-chotic medication, thus averting potentiallylethal sequelae such as death.

The neuroleptic malignant syndrome(NMS) is an uncommon but potentially fatalidiosyncratic reaction characterised by thedevelopment of altered consciousness, hyper-thermia, autonomic dysfunction, and muscu-lar rigidity on exposure to neuroleptic (andprobably other psychotrophic) medications.1 2

According to the DSM IV criteria,3 promi-nence has been given to signs of increase intemperature (>39o C) and muscular rigidity.These must be accompanied by two or moreof: diaphoresis, dysphagia, tremor, inconti-nence, altered consciousness, tachycardia,

blood pressure changes, leucocytosis andraised creatine kinase concentrations. Someresearchers have also advocated that a pyrexiain excess of 380C or 390C is necessary for thediagnosis of NMS.45 However, on reviewingthe literature since 1965, we found three pre-vious case reports highly suggestive of NMSoccurring without fever.68 We report threepatients who had all the major features ofNMS but were afebrile during the entirecourse of their illness. These cases were seenwithin a 1 year period from July 1998 to July1999.

A 52 year old man who was on treatmentfor postpsychotic depression presented afteran act of deliberate self poisoning with a

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rodenticide. As he became acutely disturbedand violent in the ward he was given severalinjections of intramuscular haloperidol, andhe received no further antipsychotic medi-cation. On the next day he developed severerigidity associated with profuse sweating andmarked autonomic instability. His heart ratewas 120 beats per minute and was irregular.His blood pressure showed wide fluctuationsand there was urinary incontinence. He thenbecame confused and went into a state ofsemiconsciousness. There was no increase inbody temperature. The creatine phosphoki-nase concentration was 1575 IU on the 2ndday and 6771 IU on the 4th day of his illness,and the white cell count was 17 000/mm3

(neutrophils 60%, leucocytes 30%, eosi-nophils 6%, macrophages 4%).As the patientdid not have any increase in body tempera-ture there was doubt as to the diagnosis. Instandard medical texts fever was recorded asa necessary finding in NMS. However, amedline search contained reports of threepatients with NMS in the absence of fever.The patient was immediately startedon bromocriptine at a dose of 2.5 mg threetimes a day. By the 5th day of treatment hiscondition improved with the autonomicdisturbances disappearing and the rigidity

subsiding. His creatine phosphokinase con-centration became normal after 5 days oftreatment.

A 20 year old man was started on 10 mgtrifluperazine twice a day for schizophreniawith catatonic features and discharged afterbeing given a depot injection of 40 mgflupenthixol intramuscularly. Five days laterhe was readmitted due to progressivelyincreasing stiVness of his body, diYculty inswallowing, drowsiness, and incontinence ofurine. On examination he was very rigid andsemiconscious, but opened his eyes to deeppain, and had severe diaphoresis whichdrenched the bed clothes. However, he hadno rise in body temperature. His heart ratewas 130 beats per minute, respiratory rate 28per minute, and his blood pressure showed

marked fluctuations. The creatine phos-phokinase assay done on the 2nd day gave2109 IU/l and the white blood cell countwas 12 400/mm3 (neutrophils 93%). Otherinvestigations including analysis of hisCSF was normal. We made a tentative diag-nosis of NMS, even though the patient didnot have fever, as we had treated a patientwith NMS presenting without fever previ-ously. The neuroleptic medication wasstopped and he was started on 2.5 mgbromocriptine three times a day. As theresponse was poor the dose was graduallyincreased to 10 mg three times a day. Hemade a relatively slow recovery and came outof the comatose state after 1 week oftreatment and autonomic disturbances andrigidity disappeared after 10 days of treat-

ment. On discharge from hospital on the14th day after starting bromocriptine hiscreatine phosphokinase was 230 IU/l.

An 18 year old boy with schizophreniawas on long term antipsychotic drugs.He was admitted with increasing stiVness ofthe body, drowsiness, and urinary inconti-nence. On examination he was rigid, had atachycardia (pulse rate 130 beats perminute) alternating with a bradycardia(pulse rate 50 beats per minute) and hisblood pressure showed wide fluctuations.There was no increase in body temperatureat admission or during the course of hisillness. The creatine phosphokinase concen-tration was 1450 IU/l on the 2nd day of his

illness and the white cell count was 15000/mm3 (neutrophils 85%). Antipsychoticmedication was stopped and he was startedon 2.5 mg bromocriptine three times a day.He made a complete recovery,with the auto-nomic disturbances and rigidity subsidingwithin 5 days of treatment. One week laterhis creatine phosphokinase was 100 IU/l.

The neuroleptic malignant syndrome usu-ally occurs with the use of therapeutic dosesof neuroleptic drugs and commonly developsduring the initial phases of treatment, whenthe drug dose is being stepped up, or when asecond drug is introduced. However, it canoccur at any time during long term neurolep-tic treatment with factors such as exhaustion,agitation, and dehydration acting as triggers.1

The above point is noteworthy especiallygiven the possibility of the occurrence of avariant and uncommon clinical picture suchas that described in our paper. There are nospecific laboratory findings, but neutrophilleucocytosis and raised creatine phosphoki-nase concentrations lend weight to thediagnosis.9

These three cases illustrate the point thatNMS can occur without fever. Our patientshad all the features of NMS apart from feverand the response to bromocriptine can be

taken as strong evidence that the diagnosiswas accurate.Beingfamiliar with this factandother diVerent ways in which this syndromecan present plus a high degree of suspicionare important in making an early andaccurate diagnosis of NMS. In fact, theappearance of muscle rigidity and clouding ofconsciousness in any patient receiving antip-sychotic medication should prompt cliniciansto suspect NMS and immediately initiateappropriateinvestigation and management. Afailure to do so may lead to delay or failure towithdraw neuroleptic medication, and thuslead to potentially irreversible sequelae andeven death. The first case also illustrates thatat times of doubt about the diagnosis of anuncommon presentation of a well describedillness, reference to the literature including animmediate Medline search could help inmaking decisions about appropriate patientmanagement.

D T S PEIRISK A L A KURUPPUARACHCHI

L P WEERASENA

Department of Psychiatry, Faculty of Medicine,

University of Kelaniya, PO Box 6, Tallagolla Road,

Ragama,Sri Lanka

S L SENEVIRATNEY T TILAKARATNA

H J DE SILVA

Department of Medicine

B WIJESIRIWARDENA

Colombo North Teaching Hospital,Ragama, Sri

Lanka

Correspondence to: Dr D T S Peiristhush@mfac.kln.ac.lk

1 Bristow MF, Kohen D. Neuroleoptic malignantsyndrome.Br J Hosp Med1996;55:51720.

2 Haddad PM. Neuroleptic malignant syndromemay be caused by other drugs. BMJ1994;308:2001.

3 American Psychiatric Association. Diagnosticand statistical manual of mental disorders. 4th ed.Washington, DC: American Psychiatric Associ-ation, 1994.

4 CaroVSN, Mann SC. Neuroleptic malignantsyndrome. Med Clin North Am 1993;77:185202.

5 Adityanjee, Singh S, Singh G, et al. Spectrumconcept of neuroleptic malignant syndrome. Br

J Psychiatry 1988;153:10711.6 Sullivan CF. A possible variant of the neurolep-

tic malignant syndrome. Br J Psychiatry 1987;151:68990.

7 Dalkin T, Lee AS. Carbamazepine and formefruste neuroleptic malignant syndrome. Br JPsychiatry1990;157:4378.

8 Hynes AF, Vickar EL. Case study: neurolepticmalignant syndrome without pyrexia. J Am

Acad Child Adolesc Psychiatry 1996;35:95962.9 Schrader GD. The neuroleptic malignant syn-

drome.Med J Aust1991;154:3012.

Acute psychosis and EEG normalisation

after vagus nerve stimulation

The acute appearance of psychosis onachievement of seizure control and normali-sationof a previously abnormal EEGhas longbeen recognised as a clinical entity termedforced normalisation.1 Focal and general-ised epilepsies are both implicated.1 Most ofthe old and new antiepileptic drugs have beenimplicated in theemergence of psychosiswithEEG normalisation.1 2

Chronic vagus nerve stimulation has beenproposed as an eVective and safe treatment ofmedically intractable epilepsy, although themechanism of action and the specific indica-tions of this treatment remain unknown. SideeVects are limited and no serious or lifethreatening damage has been reported.3

The case of a patient with medicallyintractable epilepsy who developed a

schizophrenia-like psychosis when control ofseizures and scalp EEG normalisation wereachieved through vagus nerve stimulation ispresented.

A 35 year old man had had intractable leftfrontotemporal epileptic seizures since theage of 10 years. He is right handed and leftlanguage dominant. Up to the age of 25 yearshe was almost free of seizures under treat-ment with carbamazepine and phenobarbital.After that the number of seizures graduallyincreased and secondary generalised seizuresappeared. Phenyntoin, carbamazepine, valp-roic acid, phenobarbital, vigabatrin, lamot-rigine, and clonazepam were used in diVerentcombinations without an acceptable seizurecontrol. Repeated EEG recordings during thepast few years were abnormal with prominent

slow activity, long intervals of voltage attenu-ation, and common bursts of high voltagespike wave complexes recorded mainly at theleft frontotemporal area. A high resolutionMRI was normal.

In October 1997, a vagus nerve stimulatorwas implanted because of poor seizurecontrol. During a 12 week baseline precedingthe implantation, more than 40 complex par-tial and one to two secondary generalised sei-zures every 4 weeks were noted. The patientalso experienced bursts of uncounted shortlasting complex partial seizures on a few daysevery month. At the time of implantationmedical treatment consisted of 500 mgtopiramate and 475 mg lamotrigine daily.The patient had been on this daily dose for 6months before implantation.

The stimulator output was progressivelyincreased over 1 month from implantation.The final parameters were: pulse rate 30 Hz,5 minutes oV, 30 seconds on, 1.5 mA inten-sity, and 500 ms pulse width. During thesubsequent 2 months, seizure frequency dra-matically reduced even though medicationremained unchanged. For the last 2 weeks ofthe second month he had noted only oneshort lasting complex partial seizure; at thesame time the family had noted a change inthe patients behaviour. Psychiatric evalua-tion disclosed a schizophrenia-like syndromewith auditory hallucinations, delusions ofpersecution, thought broadcasting, psycho-motor agitation, and complete lack of insight.

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