bmj - vigabatrin and psychosis · psychosis after taking an overdose of between eight and 12 g...

Journal ofNeurology, Neurosurgery, and Psychiatry 1991;54:435-439

Vigabatrin and psychosis

JW A S Sander, Y M Hart, M R Trimble, S D Shorvon

AbstractWe report a series of 14 cases ofpsychosis occurring in patients withsevere intractable epilepsy, following theprescription of vigabatrin, a new anti-epileptic drug. Nine patients had noprevious history of psychosis. In eightpatients the psychosis occurred follow-ing a change in the habitual pattern ofseizure activity; in four it developedafter a period of seizure freedom fol-lowed by a cluster of seizures, and in theother four patients an alternatingpsychosis was observed. In five patientsthere was no clear relationship to seizurepattern. Another patient developedpsychosis after taking an overdose ofbetween eight and 12 g of vigabatrin. Afurther three patients, who developedpsychosis following vigabatrin with-drawal, were not included in this series.The mean dose at onset of the psychosis(excluding the patient who took an over-dose) was 2580 mg, and the period frominitiation of therapy to the onset ofpsychosis varied from five days to 32weeks (and occurred 24 hours after theoverdose of vigabatrin). In all casesthe psychosis resolved, but necessitatedthe withdrawal of vigabatrin, except inthe single patient who took the overdose.The mechanism of this behaviour changeis unclear, but in some instances mayreflect vigabatrin's powerful anti-epilep-tic action. This is clearly not the case forall patients. Vigabatrin should be startedwith caution in patients with severeepilepsy, particularly in the presence ofa previous history of psychosis, and suchpatients should be carefully monitored.

Vigabatrin, a new anti-epileptic drug, is anirreversible inhibitor of gamma-aminobutyricacid aminotransferase (GABA-T), the maincatabolic enzyme of the cerebral inhibitoryneurotransmitter GABA. It leads to a rise inGABA concentrations in cerebrospinal fluidand in the brainl" which is believed to be thebasis of its anti-epileptic action. The efficacyof vigabatrin as a new anti-epileptic drug hasbeen established in controlled studies and ithas been shown to reduce partial and general-ised tonic-clonic seizures.''0 Vigabatrin hasrecently been registered in the United King-dom for use as an anti-epileptic drug inrefractory epilepsy.

The side effect profile of vigabatrin is notdissimilar to other anticonvulsants, especiallyin the early phases of treatment, and to dateno particular long term hazards have beenidentified. Reversible intra-myelinic oedemahas been described in early toxicity studies inexperimental animals. This was seen inrodents and beagles, but has not been seen inprimates or humans.""3

Behavioural changes associated with theinitiation of vigabatrin therapy have beenreported. Behaviour has been variouslydocumented as being improved'4 ordeteriorating."5 In investigations, however,using standardised and validated rating scales,evidence for a consistent effect on affectivesymptoms is lacking.'6More severe behavioural problems repor-

ted, sufficient in some cases to lead to with-drawal of the drug, include severe agitation7 18and psychosis.'920 We report here a series of14 cases of psychosis which occurred follow-ing the prescription of vigabatrin, some ofwhich were noted during a clinical trial of thedrug reported elsewhere.21 22

Patients and methodsDuring the past four years, we have treatedapproximately 210 patients with vigabatrin(GVG), either during the course of a clinicaltrial of vigabatrin, or during the prescription ofthe drug to patients (mostly on compassionategrounds) from the specialist clinics of theNational Hospitals for Neurology and Neuro-surgery, including the National Hospital-Chalfont Centre for Epilepsy. We identified 14patients who became psychotic after the pres-cription of the drug. None of the patients waspsychotic at the time of starting vigabatrin,although five had a history of previous psy-chosis. Here we have documented the relevantclinical details of their epilepsy and the psy-choses, and other demographic and clinicalinformation on sex, seizure type, classificationand frequency, dose of vigabatrin, IQ, pastpsychiatric history and concomitant medica-tions. Psychoses were regarded as paranoid orschizophrenia-like if the patients presentedwith an incongruent mood, hallucinations ordelusions in the setting of clear consciousness,and many of these had Schneiderian first-ranksymptoms. The term "organic psychosis" wasused when there was clear evidence of altera-tion of consciousness in association with thepsychotic phenomena. No statistical methodshave been applied to the data.

INSEG-Institute ofNeurology, NationalHospital forNeurology, Londonand the NationalSociety for EpilepsyResearch Group,Gerrards CrossJWA S SanderYM HartMR TrimbleS D ShorvonCorrespondence to:Dr Sander,National Hospital, ChalfontCentre for Epilepsy,Gerrards Cross,Buckinghamshire SL9 ORJ,UKReceived 18 May 1990and in revised form15 August 1990.Accepted 30 August 1990

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Sander, Hart, Trimble, Shorvon

Table Clinical details ofpatients

Seizure NeurologicalNo Age Sex Aetiology Age of onset classification examination EEG

01 39 M Cryptog 12 yrs B C Ataxia Right front-temp focus

02 22 F Cryptog 8 yrs D G* Normal Diffuse03 21 M Cryptog 11 yrs B C Normal Bi-temp foci04 26 F Symptom 9yrs A B C Left sided focal Right occip pariet. focus

05 20 M Symptom 2 yrs D C* Normal Diffuse with R emphasis06 28 F Symptom 2 yrs B Normal Bi-temp foci07 21 F Cryptog 3 yrs B C Normal Multifocal08 29 M Symptom 20 yrs D G* Right sided focal Slow spike and waves

09 34 M Symptom 15 yrs B C Normal Multifocal

10 31 M Cryptog 12 yrs B C Normal Bi-temp foci

11 23 F Symptom 5 yrs B C Normal Multifocal, left temp seizure recorded12 40 M Cryptog 6 yrs A B C Normal Bi-temp foci

13 25 F Cryptog 11 yrs G M* Normal General spike and waves, right sidedonset

14 32 F Cryptog 12 yrs B C Normal Bi-tenp foci

Key: Seizure classification: A = simple partial seizure; B = complex partial seizure; C = secondary generalised seizures; D = atonic seizures; G = gen. tonicclonic;M = myoclonic seizures; * = atypical absences.

ResultsThe data from the 14 cases are shown in thetable. The mean age of the patients was 28, andhalfwere female. All patients had severe refrac-tory epilepsy, identifiable causes being presentin six. With regard to the seizure type, nine hadpartial seizures with secondary generalisation,one had complex partial seizures only and thefour remaining cases had a generalised seizuredisorder. Eleven patients had a normal neuro-logical examination and the CT scan wasnormal in 11 patients.

Eight patients were on anti-epileptic drug(AED) monotherapy at the initiation of GVG,five were taking two concomitant AEDs and theremaining patient was taking three con-comitant AEDs. The commonest concomitantAED was carbamazepine (n = 11) followed byphenytoin (n = 5). EEG data revealed that fivepatients had bilateral temporal changes, onehad a right fronto-temporal focus, and one hada right occipito-parietal focus. Three patientshad multifocal abnormalities in their EEG, andin one of these seizures originating in the lefttemporal region were recorded on telemetry.The remaining four patients had generalisedabnormalities; in one, however, seizure record-ing showed initial ictal electrographic activitywidely over the right hemisphere.Nine patients had no previous history of

psychosis, although two of these patients had along history of behavioural disorders and onehad a previous diagnosis of anorexia nervosa.Two patients had had an earlier psychoticepisode when clobazam was prescribed and theremaining three patients had an earlier historyof interictal psychosis not associated withseizures or drugs.The pattern of seizures in eight of these

patients was of particular interest, with fourpatients falling into each of two readily identi-fiable patterns. In the first (pattern 1), patients(3, 8, 9, and 10) became seizure free fairly soon,or virtually so, following the introduction ofvigabatrin, only to develop a cluster ofseizures,following which the psychosis erupted (in all

within five days and in most within 48 hours ofthe cluster). The clinical diagnosis in three wasof a schizophrenic psychosis with auditory andvisual hallucinations and religious delusions.The fourth developed a twilight state withvisual hallucinations and delusions. In thispattern, in all patients the period of seizurefreedom was unusually long, and somepatients' notes contained comments such as"this is the longest ever free of attacks",identifying the change of pattern. In one caseEEG recordings were obtained after the seizurecluster when the patient was psychotic. Therecord had normalised in contrast to recordingstaken in the pre-treatment, pre-psychotic state(fig 1). In patients 3 and 9, the psychosisresolved on halving the dose of vigabatrin, onlyto recur after a period of five weeks to fourmonths without a seizure cluster, necessitatingcomplete withdrawal of the drug.

In the other pattern (pattern 2), the patientsbecame seizure free, and developed the psy-chosis some time after the onset of the seizureremission. The time elapsing varied from tendays to six weeks. This pattern was seen in fourcases (patients 6, 7, 11 and 14). Three of thesepatients had a schizophrenic-like psychosis,and the fourth had an organic psychosis. EEGrecords in two patients with pattern 2 showsome evidence of forced normalisation23 24 (oneexample is shown in fig 2). This is the changefrom a patient's usual abnormal interictalEEG, during the non-psychotic state, to anormal or near normal EEG during thepsychosis.

It is worth noting that two of these patientshad had an earlier psychotic episode when theirseizures were treated and remitted in a similarway. Both (patients 6 and 11) were then pres-cribed clobazam, although at the time patient11 also had phenytoin toxicity. Patient 14 had aprevious history of interictal psychosis notclearly relatedto her seizure pattern. Patients 1,2, 4, 5 and 13 developed psychiatric distur-bances after initiation of vigabatrin with noclear relation to seizure pattern. Patient 1 had a

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Full Concom Initial therapy Dose ofCT IQ AEDs Past Psychiatric history Psychiatric diagnosis to episode Pattern GVG

Normal 80 CBZ Organic psychosis Organic psychosis 2 weeks n/a 2-0 gSVPCZP

Normal 82 CBZ Behav disturbances Schiz like psychosis 3 weeks n/a 2-5 gRight temp lesion 117 CBZ Nil Schiz like psychosis 12 weeks Type 1 4-0 g

DPHNormal 87 CBZ Nil Schiz like psychosis 6 weeks n/a 20 gNormal 61 CBZ Behav disturbances Paranoid state 3 weeks n/a 3 0 gNormal 93 CBZ Similar episode on COZ Schiz like psychosis 4 weeks Type 2 3-0 gNormal 92 DPH Anorexia nervosa Organic psychosis 2 weeks Type 2 2-0 gNormal 96 CBZ Nil Schiz like psychosis 5 weeks Type 1 30 g

DPHNormal 118 DPH Nil Schiz-manic 32 weeks Type 1 40 g

PRMNormal 122 CBZ Nil Twilight state/Org psychosis 5 weeks Type 1 40 g

DPHOccip lesion 80 CBZ Similar episode on COZ Schiz like psychosis 4 weeks Type 2 1 5 gNormal 94 CBZ Nil Organic psychosis 1 day after GVG n/a ?8-12 g

SVP overdoseNormal 87 CBZ Psychosis Schiz like psychosis 5 days n/a 0-5 g

Mild atrophy 88 PRM Schiz like psychosis Schiz like psychosis 6 weeks Type 2 2 0 g

Anti-Epileptic Drugs (AEDs): CBZ = carbamazepine; COZ = clobazam; CZP = clonazepam; DPH = phenytoin; GVG = vigabatrin; PRM = primidone;SVP = sodium valproate.

previous history of recurrent psychosis, anddeveloped a florid organic psychosis two weeksafter the start ofvigabatrin. Patient 2 developedan organic psychosis after starting vigabatrin.She had ceased to have generalised attacks,although atypical absences continued unabatedat an increased rate. She had diffuse abnor-mality on EEG. Patient 4 developed psychoticsymptoms after being seizure free for 17 days,six weeks after starting the drug, but had hadprevious episodes in which she had beenseizure free for up to three months withoutpsychiatric disorder. She had, however, beenhaving almost daily seizures in the periodimmediately before starting vigabatrin. Patient5 developed a paranoid state three weeks afterstarting vigabatrin. His seizure pattern wasunchanged. Patient 13 became psychotic fivedays after starting vigabatrin, during whichtime she had continued to have atypicalabsences.

Patient 12 developed a psychotic episodelasting 36 hours after having taken an overdoseof between eight and 12 g of vigabatrin duringpost-ictal confusion. The mean dose ofvigabatrin at the onset of psychosis was 2500mg (excluding patient 12) with a range of 500mg to 4000 mg. All patients made a fullrecovery, and in all but one patient (patient 12)vigabatrin has now been stopped. Threepatients (1, 6 and 14) required neurolepticdrugs.We have also noted the development of

psychosis within days of the withdrawal ofvigabatrin in a further three of our patients notdocumented above; two of these patients wereadmitted to hospitals other than our own.

DiscussionIt is well recognised that patients with chronicepilepsy may present with interictal psychosisor episodic psychosis related to drug therapy.Nevertheless, since the advent of GVG, wehave noted an increased incidence of suchcases, to an extent which is not associated withany of the major anti-epileptic drugs nor otherdrugs on clinical trial in our unit. We report

here 14 patients who developed a psychosisafter starting vigabatrin. Although isolatedcases of psychosis have been noted as a possibleside effect ofthis drug in clinical trials'9 20 to datethere has been no attempt at documenting suchcases from the clinical and EEG viewpoint.

Psychosis in these patients in associationwith GVG has followed a cluster of seizures(post-ictal psychosis-pattern 1), a period ofseizure freedom (altemating psychosis-pattem 2), withdrawal of anti-epileptic drugs,drug overdose, or in some cases occurredindependently of all these factors.

In pattern 1 (4 cases), patients had suppres-sion of their seizures following drug initiation,and then suddenly had a burst or cluster ofseizures (representing a change in pattem)which was followed by the psychosis. Psychoticepisodes were short lasting, and resolved withreduction or withdrawal of the vigabatrin. Inthe two patients who had the dose reduced,however, there was a subsequent recurrence ofthe psychosis (without a seizure cluster), neces-sitating the complete withdrawal of the drug.In pattem 2 (4 cases), an altemating psychosisoccurred with EEG evidence in two (patients 6and 14) of forced normalisation (fig 2). Theremaining six cases did not fit clearly into eitherofthese two patterns. Two ofthese patients hadhad a previous history of psychosis, however,and a third developed psychosis after an over-dose ofvigabatrin. In addition to these 14 cases,three further patients were seen who developedpsychosis on withdrawal of vigabatrin.The literature on post-ictal psychosis is

limited, and such states, while being commonin practice, are not well documented. In thelargest series, that of Levin,25 clinical featuressimilar to our cases in pattern 1 were noted, andit was reported that the onset could be up toseven days after the seizures. Two or moreattacks usually preceded the psychosis. In themore recent series of Logsdaile and Toone,26clusters were again a frequent herald to thepsychosis, and there was often a lucid intervalof several (up to six) days before the psychosisappeared.

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Figure 1 showing EEG recordings ofpatient 9 (A, interictal, before vigabatrduring the psychotic episode), demonstrating the marked improvement in theduring the psychotic phase.

The second pattern is also well rethe literature. Of interest in our serietwo cases the EEG showed markedment during the psychotic phasewith previous EEGs. Landolt2324 cphrase "forced normalisation" whported a group of patients whopsychosis with epilepsy, and noted t]these episodes, seizures abated arlogical EEGs normalised. He pointe

such attacks could last several weeks, and theyU could be provoked by anticonvulsant therapies.

Further, the psychoses could be relieved byECT, or a spontaneous seizure, and the EEGwould revert to its previous abnormal state.Although the term forced normalisation maynot have been well chosen, similar events havenow been well documented.27 In many settings,confirmation of the EEG changes is not pos-sible, and Tellenbach' introduced the term

.,1.... ..... alternating psychosis as a clinical expression ofthe alternation between seizures or psychosis asseen in these cases. In his earlier work Landolttended to emphasise a relationship to temporallobe epilepsy and partial seizures, although helater noted cases in association with generalisedseizure disorders.

TL.e possibility that anticonvulsant drugsplayed a role in the development of these stateswas earlier raised by Gibbs' in trials withphenacetylurea (phenurone), and in Landolt'sstudies, particular attention was drawn to thesuccinimides. Wolf2730 has reinforced this sug-gestion, noting especially a link between gen-eralised seizures, alternating psychoses andethosuximide. In his studies valproic acid wasnot associated in the same way, although otherauthors have described cases of forced normal-isation on this anticonvulsant.3' Wolf specu-lates that disturbed sleep is an early manifesta-tion of the ethosuximide induced alternatingpsychosis, this drug sometimes provokingarousal.27 0 It is of interest that of the anti-convulsants tested using Critical FlickerFusion (CFF), a measure of cortical arousal, alldecrease values, with the exception of viga-batrin,32 and clobazam.33 It is the more remark-able therefore that two of our cases hadprevious episodes of alternating psychosiswhile on clobazam with similar clinicalfeatures. Although the influence of etho-suximide on CFF is untested, these ideas are inkeeping with the views of Wolf.The relationship between GABA and psy-

chosis is unclear. At first sight a GABA agonistmay be expected to be antipsychotic. GABAlevels in schizophrenic brain material and inCSF are probably normal,34 3 and theoreticallya GABA agonist should antagonise dopaminerelease. Certainly the acute rise in CSFhomovanillic acid (HVA) noted on treatmentwith vigabatrin is similar to that seen withtypical neuroleptics.3 In contrast, the knownGABA pathways from limbic forebrain areassuch as the nucleus accumbens to ventral

-__-_--_ pallidum and the ventral tegmental area sug--in, B, gest possible associations between vigabatrin,EEG GABA and anatomical pathways thought to be

involved in the pathogenesis ofthe psychoses.36Further work in this area is urgently required.

-corded in Vigabatrin is a potent anti-epileptic drug,.s is that in and in our experience2l 22 and that of others,>'0improve- has been highly effective in controlling seizurescompared in some patients. All our patients had severe,oined the epilepsy and had been prescribed vigabatrinten he re- only after conventional anti-epileptic treat-developed ment had failed. The role of vigabatrin in thehat during development ofpsychosis in these patients mayad patho- be due to a number of factors. In the casesd out that exhibiting patterns 1 and 2, the psychosis may

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Figure 2 showing EEG recordings of patient 6 (A, before vigabatrin, B, during thepsychotic episode), shows features similar to that offigure 1.

result from an alteration in seizure activity.Furthermore, it is common clinical experiencethat epileptic psychosis is more frequent inpatients with severe epilepsy; all patients in thisseries had a severe and intractable seizuredisorder and over one third had a previoushistory of psychosis. Whatever the mechanismof the psychosis, and the relationship betweenthis and the prescription of vigabatrin, wewould urge caution when starting vigabatrin,particularly in patients with a previous historyof psychosis or with severe chronic epilepsy.Other behaviour disturbances were also seen insome of our patients, including agitation, con-fusion, hyperactivity, stupor and depressionand certainly in our series and others, be-haviour changes were the most common im-portant side effect of this anti-epileptic drug.We are very grateful for the support of Merrell-Dow in ourstudies on vigabatrin. We are also grateful for the support of theNational Society for Epilepsy, Sir Jules Thorn Charitable Trust,the Action Research for Crippling Diseases, and the BrainResearch Trust. We thank Dr David Fish for his helpfulcomments on the EEGs of our patients.

1 Jung MJ, Lippert B, Metcalf BW, Bohlen P, Schechter PJ.

Gamma-vinyl-GABA (4-amino-hex-5-enoic-acid), a newselective inhibitor of GABA-T: effects on brain GABAmetabolism in mice. JNeurochem 1977;29:797-802.

2 Schechter PJ, Hanke NF, GroveJ, Huebert N, Sjoerdsma A.Biochemical and clinical effects of gamma-vinyl-GABA inpatients with epilepsy. Neurology 1984;34:182-6.

3 Ben-Menachem E, Persson LI, Schechter PJ. Effects ofsingle doses of vigabatrin on CSF concentrations ofGABA, homocarnosine, homovanillic acid and 5-hydroxyindolacetic acid in patients with complex partialepilepsy. Epilepsy Res 1988;2:96-101.

4 Gram L, Larsson OM, Johnsen A, Schousboe A. Experi-mental studies of the influence of vigabatrin on the Gabasystem. Br J Clin Pharmac 1989;27:13S-7S.

5 Rimmer EM, Richens A. Double-blind study of gamma-vinyl-GABA in patients with refractory epilepsy. Lancet1984;i:189-90.

6 Gram L, Klosterkov P, Dam M. Gamma-vinyl-GABA: adouble-blind, placebo-controlled trial in partial epilepsy.Ann Neurol 1985;17:262-6.

7 Loiseau P, Hardenberg JP, Pestre M, Guyot M, SchechterPJ, Tell GP. Double-blind, placebo-controlled study ofvigabatrin in drug resistant epilepsy. Epilepsia 1986;27:115-20.

8 Tartara A, Manni R, Galimnberti CA, Herdenberg J, OrwinJ, Perucca E. Vigabatrin in the treatment of epilepsy: adouble-blind, placebo-controlled study. Epilepsia 1986;27:717-23.

9 Tassinari CA, Michelucci R, Ambrosetto G, Salvi F.Double-blind study of vigabatrin in the treatment of drug-resistant epilepsy. Arch Neurol 1987;44:907-10.

10 Mumford JP, Dam M. Meta-analysis of European placebocontrolled studies of vigabatrin in drug resistant epilepsy.BrJ Clin Pharmac 1989;27:101-7S.

11 Butler WH, Ford GP, Newberne JW. A study of the effects ofvigabatrin on the central nervous system and retina of rats.Toxicol Pathol 1987;15:143-8.

12 Pederson B, Hojgaard K, Dam M. Vigabatrin: no micro-vacuoles in human brain. Epilepsy Res 1987;1:74-6.

13 Anon. Vigabatrin (editorial). Lancet 1989;i:532-3.14 Chauvel T, Vignal JP, Trottier S, Beaumont D. Long term

follow up of vigabatrin treated patients with partial seizures.Abstracts: 18th Epilepsy International Congress; NewDelhi, India, 1989:140.

15 Birbeck KA, Ossetin J, Ring HA, Farr I, Heller A, ReynoldsEH. Vigabatrin and mood. Abstracts: 18th Epilepsy Inter-national Congress; New Delhi, India, 1989:78.

16 McGuire A, Duncan JS, Trimble MR. Effects of vigabatrinin cognitive function and mood, when used as an add-ontherapy in patients with intractable epilepsy. Epilepsia1990 (in press).

17 Livingston JH, Beaumont D, Arzimanoglou A, Aicardi J.Vigabatrin in the treatment of epilepsy in children. Br JClin Pharmac 1989;27:109-12S.

18 Luna D, Dulac 0, Pajot N, Beaumont D. Vigabatrin in thetreatment of childhood epilepsies: A single-blind placebocontrolled study. Epilepsia 1989;30:430-7.

19 Faedda MR, Iani C, Paris L, Fusco L, Manfredi M, Ash-Rogers G, Mumford JP. Clinical results of vigabatrintreatment in patients with refractory epilepsy. Abstracts:17th Epilepsy International Congress; Jerusalem, Israel,1987:59.

20 Ben-Menachem E, Persson L, Mumford J. Long-termevaluation of once daily vigabatrin in drug-resistantpartial epilepsy. Epilepsy Res 1990;5:240-6.

21 Sander JWAS, Hart YM. Vigabatrin and behaviour distur-bances. Lancet 1990;i:57.

22 Sander JWAS, Trevisol-Bittencourt PC, Hart YM,Shorvon SD. Evaluation of vigabatrin as an add-on drugin the management of severe epilepsy. J Neurol NeurosurgPsychiatry 1990;53:1008-10.

23 Landolt H. Some clinical EEG correlations in epilepticpsychoses. Electroencephalogr Clin Neuro 1953;5:121.

24 Landolt H. Serial EEG investigations during psychoticepisodes in epileptic patients and during schizophrenicattacks. In: Lorenz de Haas AM, ed. Lectures on Epilepsy.Amsterdam: Elsevier, 1958:91-133.

25 Levin S. Epileptic clouded states. JNerv Men Dis 1952;116:215-25.

26 Logsdaile S, Toone B. Post-ictal psychoses. Brit J Psychiat1988;152:246-52.

27 Wolf P. Forced Normalisation. In: Trimble MR, Bolwig T,eds. Aspects of Epilepsy and Psychiatry. Chichester: JWiley, 1986:101-15.

28 Tellenbach H. Epilepsie als Anfallsfeiden und als Psychose.Nervenartz 1965;36:190-202.

29 Gibbs FA. Ictal and non-ictal psychiatric disorders intemporal lobe epilepsy. J Nerv Men Dis 1951;113:522-8.

30 Wolf P. Forced Normalisation. In: Smith DB, Treiman D,Trimble MR, eds. Neurobehavioural Problems in Epilepsy:Scientific basis, Insights and Hypotheses. New York: RavenPress, 1991:127-42.

31 Pakalnis A, Drake ME, Kuruvilla J, Blake K. ForcedNormalisation. Arch Neurol 1988;44:289-92.

32 Morrow JI, Richens A, Gisselbrecht D, Mumford J. A longterm placebo controlled study of vigabatrin in resistantepilepsy with reference to dose and toxicity evaluation.Abstract: 18th Epilepsy International Congress; NewDelhi, India, 1989:26.

33 Hindmarsh I. The psychopharmacology of clobazam. RSMInt Congress and Symposium Series, 74. London: RSM,1985:3-10.

34 Von Kammen DP, Sternberg DE, Harle TA, Walters RN,Bunney WE. SCF levels ofGABA in schizophrenia. ArchGen Psychiat 1982;39:91-7.

35 Cross AJ, Crow TJ, Owen F. GABA in the brain inschizophrenia. Lancet 1979;i:560-1.

36 Trimble MR. Biological Psychiatry. Chichester: J Wiley,1988.

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Book reviews

in the book leading to unnecessary complex-ity which in my view interrupts the flow whenreading. Overall Professor Al-Mefty hasachieved his aim of embodying the progresswhich has occurred in the fifty years sinceCushing and Eisenhardt published theirmonograpn on meningbomas.

Essentials of NeuroimagingWOOD. (Pp 497; Illustrated. F

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This book is an attempt tcoverview of Neuroimaging anclinical management forNeuroradiology, Neurology argery. There are twelve chapteintracranial pathology, includintwo to the spine.The first chapter, dealing wi

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ters is better balanced, bothclinical topics and radiological iIThe role of each imaging metho4and emphasis placed on conditi(importance. Revision lists are

strategically placed boxed inseout. The method works well indealing with intracranial disordin the spine where insufficient ston the increasing importanceResonance. The illustrations,numerous, well chosen and genequality, are the chiefstrength ofmake it worthy of study.Here is a brave effort to covei

range of clinical activity. It inedepth and unfortunately the irniques themselves are dispresented.

I I

Tremor By RJ ELBLE AND WC KOLLER. (Pp204; Price: $39.50). Baltimore, The JohnsHopkins University Press. 1991. ISBN 0-8018-4024-4

MDM SHAW Despite its high population prevalence, in

publishing terms tremor has always been thepoor relation to Parkinson's disease. Thus,other than the multi-author book edited byFindley and Capildeo in 1984, I am not awareof any other volumes devoted to the subject.Thus "duograph" by Elble and Koller

By j R KIRK- admirably fills the gap. It is one of that select'rice £65.00). band of neurology books that is actuallygstone, 1990. produced with the reader in mind. Thus, it is

not too big, not too heavy and not too long,and divided into bite-sized chapters that can

provide an even be tackled in a standing position on theid its role in Northern Line. The book itself is welltrainees in produced and printed and, miraculously for aad Neurosur- first edition, I could detect only one typo-rs devoted to graphical error in the text itself. The list ofkg trauma, and 786 references is at the end of the book, and

each chapter ends with a summary. Thisith techniques latter feature is particularly useful forTwenty-eight innumerates like myselfwho might balk at thedescription of sight of seemingly complex equations in theight to Mag- chapter on measurement of tremor.alf a page to The authors tell us clearly and conciselyh is dismissed not only what we do know about tremor butme principles also, just as importantly, expose considerablelide scanning areas ofuncertainty. Thus, after reading bothar briefly in a sides of the arguments, we learn how many ofcular disease. the questions concerning the whereabouts ofrits of digital tremor generators, the significance of alter-

nating versus co-contracting EMG patterns,Weeding chap- and the capacity of peripheral perturbationsin regard to to reset certain tremors, are still open andnvestigations. undecided. To take another example, whered is discussed does enhanced physiological tremor end andons of clinical benign essential tremor begin (not known),provided in and can tremor recordings distinguish be-

.rts through- tween them? (no).the sections It is difficultto find fault. However, the 1955

iers, less well paper by Schwab and Chafetz concernedtress is placed procyclidine, not amantadine. Perhaps dys-of Magnetic tonic tremor could have been given morewhich are space, the tremor ofdysgammaglobulinaemic

erally of good neuropathy a mention, and the usefulness ofthis book and jaw tremor in distinguishing between parkin-

sonian and essential tremor might have beenr a very wide addressed, but these are only minor quibbles.vitably lacks Overall this is an excellent book. It shouldmaging tech- be a part of all neurological libraries, andsappointingly many neurologists will also wish to have a

personal copy on their shelves.ISHERWOOD NIALL QUINN

Neural Transplantation: FromMolecular Basis to Clinical Applica-tions. Progress in Brain Research Vol 82.Edited by SB DUNNETT AND S-J RICHARDS. (Pp743 Illustrated; Price: Dfl 440). 1990. Amster-dam, Elsevier Science Publishers BV. ISBN0-444-81137-0

This volume records some of the paperspresented at the Symposium on NeuralTransplantation in 1989. It is already twoyears out of date and is published only one

year before the next Symposium on thissubject is due to take place. However it bringswithin the covers of one volume a compre-hensive review of knowledge and experiencein this field to 1989.There are few areas of basic and clinical

research where there is a more pressing needfor an understanding of biological mechan-isms and their clinical application than in thefield of neural transplantation. This volumehas sections devoted to genetic manipulationof cells for neural grafts, immunological con-siderations in the brain, and extensive reviewof experience of glial and neuronal grafting inanimals. Finally there are reports of clinicalexperience with adrenal and nigral grafts.This is a useful book because it provides

information on the experience of most of thecentres with an active programme of researchin 1989. Inevitably most of the papers posemore questions than they answer but progresshas been so rapid that some of the answers arealready available in subsequent publications.This book is an essential reference work for

the library of any institution where neuraltransplantation research is being done. It isalso a valuable source of data and referencesfor anyone seeking information in this rapidlyadvancing area of neuroscience.

R GODWIN-AUSTEN

Erratum

Vigabatrium and psychosis-JNNP1991;54:435-9.The authors omitted the following paragraphfrom the "Patients and methods" section:

The illustrated awake EEG recordings werecarried out using the standard 10/20 system ofelectrode placement, an amplitude of100 mV/cm and a paper speed of 30 mm persecond (the time marker in seconds is shownat the top of each illustration), with a highfrequency filter of 120 Hertz (fig I b, 2a and 2b)or 60 Hertz (fig la) and a time constant of 0-3second.

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bmj - vigabatrin and psychosis · psychosis after taking an overdose of between eight and 12 g...

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