106 J Neurol Neurosurg Psychiatry 1999;67:106–108 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.1.106 on 1 July 1999. Downloaded from

SHORT REPORT

Focal (segmental) dyshidrosis in

Kazumasa Sudo, Naoto Fujiki, Sachiko Tsuji, Minoru Ajiki, Takuya Higashi, Masaaki Niino, Seiji Kikuchi, Fumio Moriwaka, Kunio Tashiro

Abstract Methods The features or mechanisms of dyshidro- PATIENTS AND METHODS sis have not been suYciently clarified. We have stored clinical data of a consecutive 34 Neither has the diVerence between hyper- patients (0.28%) with MRI confirmed syringo- hidrosis and hypohidrosis. To clarify the myelia and Chiari malformation among the 11 features and mechanisms of dyshidrosis 967 outpatients who visited our (hyperhidrosis and hypohidrosis) in sy- clinic from April 1989 to November 1996. ringomyelia, the clinical features focusing Three quarters of the patients came without on hidrosis of 30 patients with syringomy- referral, and a quarter came with referral. Our elia and Chiari malformation located outpatient clinic is not only a primary but also from a syringomyelia database were pro- a secondary and tertiary centre for diagnosis spectively analysed. The patients were and treatment of all neurological disorders. classified into three groups: eight patients The case records of each patient showed that (26.7%) had segmental hypohidrosis, 10 there had been no referral bias to our clinic as (33.3%) had segmental hyperhidrosis, and a consequence of our interest in dyshidrosis in 12 (40.0%) had normohidrosis. We found syringomyelia. The protocol includes items for that the Karnofsky functional status for the autonomic as well as other the hyperhydrosis and normohidrosis systems. The data were obtained prospectively, groups were significantly higher than for with the intention of avoiding any predetermi- the hypohidrosis group (p=0.0012), with nation bias, according to a protocol for no significant diVerences between the examining patients with syringomyelia, which hyperhidrosis and normohidrosis groups. we ourselves designed. At the time of regis- The duration from the onset of syringo- tration for this study, we obtained informed myelia to the current dyshidrosis was sig- consent from patients to enter their infor- nificantly longer in the hypohidrosis mation into our study database. Four of the 34 group than in the hyperhidrosis group patients were dropped from the study because http://jnnp.bmj.com/ (p=0.0027). A significant correlation was they refused to give us permission to employ identified between the duration from the clinical information about themselves for any onset of syringomyelia to the time at study clinical study; this left 30 patients. Twelve of and the performance score (r=−0.599, these patients were operated on for syringomy- Department of p=0.0003). The results substantiate previ- elia, and we completed entering their infor- Neurology, Hokkaido ous hypotheses that in its early stage mation at the time of the operation. University School of Medicine, Sapporo, syringomyelia causes segmental hyperac- on September 24, 2021 by guest. Protected copyright. Japan tivity of the sympathetic preganglionic PROTOCOL FOR EXAMINING DYSHIDROSIS K Sudo neurons, and hyperactivity of these gradu- We obtained detailed clinical information for N Fujiki ally subsides as tissue damage progresses. each patient, including their previous experi- S Tsuji Focal hyperhidrosis may be regarded as a ence of hidrosis. A structured protocol was M Ajiki hallmark of a relatively intact , T Higashi used to examine the state of hidrosis: step 1 M Niino as well as normohidrosis. asking about the nature and distribution of the S Kikuchi (J Neurol Neurosurg Psychiatry 1999;67:106–108) hidrosis and the eVects of room temperature, F Moriwaka exercise, clothing, psychological burdens, food, K Tashiro Keywords: syringomyelia; Chiari malformation; dyshid- rosis; sympathetic preganglionic neuron etc; step 2 examining the state of hidrosis by Correspondence to: observation, manual examination, and drawing Dr Kazumasa Sudo, a metal spoon across the surface of the skin Department of Neurology, Syringomyelia is responsible for dyshidrosis as (spoon test12) either after adequate physical Hokkaido University School of Medicine, Kita 14, Nishi well as other disorders of the autonomic nerv- exercise or when lying in a bed warmed in 1–4 5, Kita-Ku, Sapporo, ous system. Although the link between syrin- advance by electric blankets. When further 060–8648 Japan. Telephone gomyelia and focal dyshidrosis (hyperhidrosis investigation was necessary to clarify the nature 0081 11 716 1161, ext 6028; fax 0081 11 700 5356; email and hypohidrosis) has been described, no and distribution of dyshidrosis, the following [email protected] adequate notice has been taken of the steps were performed; step 3 taking a thermo- phenomenon,1 5–8 nor has its mechanism been graph in a room at a temperature of 21–28°C; Received 6 July 1998 and in properly explained.1–3 9–11 Furthermore, no de- step 4 a hidrosis examination (the iodine-starch revised form ° 7 January 1999 scriptions have been oVered of any relation method) at a room temperature of 45–50 C, or Accepted 19 January 1999 between hyperhidrosis and hypohidrosis. in a bed warmed in advance. Consequently we Focal (segmental) dyshidrosis in syringomyelia 107 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.1.106 on 1 July 1999. Downloaded from

Thermograph of patient 18 before (A) and 11 days after (B) surgical decompression of syrinx (anterior views). Temperature asymmetry has resolved immediately after decompression of the syrinx. performed thermography in 16 patients, and to time of study, K score, and duration of the iodine-starch method in nine patients. We follow up period) for the three groups of assessed the performance status by Karnofsky patients (hyperhidrosis, normohidrosis, and performance score (K score); this ranges from hypohidrosis) by one way factorial analysis of 0 to 100, and the higher the score, the better variance (ANOVA) (Fisher’s PLSD method as the performance.13 a post hoc test), and for two factors (age of onset of current dyshidrosis and duration from CASE RECORDS onset of symptoms to current dyshidrosis) (See also our previous case records for three between the two groups of patients (hyperhid- patients with hyperhidrosis14). rosis and hypohidrosis) by non-paired t test. We Patient 18 (hyperhidrosis; 37 year old then obtained the Pearson’s correlation coef- woman) had a 7 month history of persistent ficient for duration from onset of symptoms to hyperhidrosis and pain in the left upper quad- time of study, and K score for all 30 patients. rant of the body. There was no muscle weakness or atrophy. Thermography showed Results low temperature in the left upper quadrant, Of the 30 patients, eight (26.7%) had hypohid- which was consistent with hyperhidrosis of the rosis, 10 (33.3%) had segmental hyperhidrosis, area (figure A). She underwent an operation (a and 12 (40%) had normohidrosis. In all syringosubarachnoid shunt) 7 months after patients, the distribution of dyshidrosis corre- onset, after which hyperhidrosis and pain sub- sponded with the location of the syrinx and sided within a week, as indicated by thermog- other neurological manifestations; the syrinx raphy (figure B). was located roughly in the region from the cen- tral canal to the unilateral (or sometimes bilat- STATISTICAL ANALYSIS eral with asymmetry) posterior angle of the

We performed a statistical analysis of five spinal cord. http://jnnp.bmj.com/ factors (age at time of study, age of onset of We have summarised the results of the statis- symptoms, duration from onset of symptoms tical analyses in the table. Although we Table 1 Summary of evaluation of each item

Item Hypohidrosis Hyperhidrosis Normohidrosis p Value Number of patients 8 10 12 Ageattimeofstudy:

Range (y) 17-71 18-75 19-75 on September 24, 2021 by guest. Protected copyright. Mean (SD) 45.4 (22.7) 39.2 (17.9) 42.9 (18.8) 0.7982* Age of onset of symptoms: Range (y) 2-55 5-45 10-69 Mean (SD) 21.5 (16.4) 23.8 (13.6) 33.3 (16.2) 0.2008* Duration from onset of symptoms to study: Range (y) 8-45 1-33 1-32 Mean (SD) 23.9 (13.3) 15.5 (10.1) 9.67 (9.61) 0.0273*{ Karnofsky performance score: Range 50-90 60-90 70-90 Mean (SD) 65.0 (16.9) 85.0 (9.72) 83.3 (6.51) 0.0012*§¶ Follow up period: Range (y) 1-9 1-9 1-8 Mean (SD) 3.38 (3.25) 5.00 (3.74) 2.83 (2.76) 0.2960* Age of onset of current dyshidrosis: Range (y) 16-66 13.50 — Mean (SD) 42.3 (21.0) 29.2 (13.5) — 0.1287† Duration of onset from symptoms to current dyshidrosis: Range (y) 7-45 0-15 — Mean (SD) 12.6 (4.5) 5.50 (4.70) — 0.0027†§

*One way factorial ANOVA (Fisher’s PLSD method). †Non-paired t test. §Statistically significant. {p value for each pair of items: hyperhidrosis v hypohidrosis 0.1148; hypohidrosis v normohidrosis 0.0078; normohidrosis v hyper- hidrosis 0.2194. ¶p value for each pair of items: hyperhidrosis v hyperhidrosis 0.0007; hypohidrosis v normohidrosis; 0.7282; normohidrosis v hypo- hidrosis 0.0012. 108 Sudo, Fujiki, Tsuji, et al J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.1.106 on 1 July 1999. Downloaded from

ourselves were not able to confirm any change SPGNs, consistent with the clinical history of in the features of hidrosis during the follow up five of our eight patients with hypohidrosis. By period, the clinical histories of five patients contrast, immediate resolution of hyperhidrosis indicate that hidrosis decreased segmentally or after decompression of the syrinx in patient 18, diVusely over a long period. Duration from whose disability was minimal, showed that the onset of symptoms to study was significantly damage to the SPGNs was mild and tends to longer in the hypohidrosis group than the nor- be reversible in patients with mild disability mohidrosis group (ANOVA; F(2, 27)=4.127, (figure). Before we reached the above hypoth- p=0.0273) (table). The K scores were signifi- esis for the mechanism of hyperhidrosis, we cantly higher in the hyperhidrosis and normo- had ruled out the possibility of interference to hidrosis groups than in the hypohidrosis group the inhibitory tract that connects the upper (ANOVA; F(2, 27)=8.765, p=0.0012), with no centre and the SPGNs as before because of the significant diVerence between the hyperhidro- segmental distribution of hyperhidrosis and sis and normohidrosis groups (p=0.7282). because of the locational relation among the Duration from onset of symptoms to current syrinx, inhibitory tracts, and SPGNs.14 16 dyshidrosis was significantly longer in the Current results substantiate previous specu- hypohidrosis than in the hyperhidrosis group lation about the mechanism of and relation (p=0.0027). There were no significant diVer- between hyperhidrosis and hypohidrosis in ences between hidrosis groups in the other fac- syringomyelia.3914We now think that, in syrin- tors. A significant correlation between the two gomyelia, focal hyperhidrosis can be regarded items (duration from onset of symptoms to as a hallmark of a relatively intact—even study, and K score) was recognised (r=−0.599, though slightly damaged—spinal cord. We also n=30, p=0.0003). think that, in syringomyelia, some part of nor- mohidrosis is associated with a considerable Discussion amount of spinal cord damage. We propose We performed a MEDLINE search for publi- that in diagnosing focal dyshidrosis, more cations dealing with dyshidrosis in syringomy- attention should be given to the possibility of elia between January 1966 and June 1997, with syringomyelia. a language limitation of English, German, and French. This search confirmed the scant accu- We are indebted to Drs Kazutoshi Hida, Yoshinobu Iwasaki, and mulation of information regarding dyshidrosis Hiroshi Abe (Department of Neurosurgery, Hokkaido Univer- sity School of Medicine) for their help in providing us with in syringomyelia; we were able to locate only clinical information regarding surgical treatment. This study four cases accompanied by Chiari malforma- was supported by Research Grant (5B-3) for Nervous and Mental Disorders, from the Japanese Ministry of Health and tion (three of which we have already reported Welfare. and are currently included in this study).10 14 We previously speculated that hyperhidrosis 1 Spillane JD. Syringomyelia. An atlas of clinical neurology. is caused by stimulation of sympathetic pregan- London: Oxford University Press, 1968:254–63. glionic neurons (SPGNs) rather than interfer- 2 Foster JB, Hudgson P. The clinical features of communicat- 14 ing syringomyelia. In: Barnett HJM, Foster JB, Hudgson P, ence to the inhibitory tract. This is equivalent eds. Syringomyelia. London: WB Saunders, 1973:16–29. to the hypothesis regarding body hypertrophy 3 Schliep G. Syringomyelia and syringobulbia. In: Vinken PJ, which we recently presented.4 Later, disinhibi- Bruyn GW, eds. Handbook of clinical neurology. Amsterdam:

North-Holland, 1978:255–327. http://jnnp.bmj.com/ tion of the inhibitory local interneurons 4 Sudo K, Owada Y, Yabe I, et al. Syringomyelia as a cause of body hypertrophy. Lancet 1996;347:1593–5. (ILINs), which are located in the vicinity of 5 Nudleman K, Andermann E, Andermann F, et al. The hemi SPGNs, was supposed to be the cause of 3 syndrome. Hemihypertrophy, hemihypaesthesia, hemi- 10 areflexia and scoliosis. Brain 1984;107:533–46. segmental hyperactivity of the SPGNs. When, 6 Mancall EL. Syringomyelia. In: Rowland LP, ed. Merritt’s in the clinical course of syringomyelia, slowly textbook of neurology. 8th ed. Philadelphia: Lea and Febiger, 3 1989:687–91. progressive tissue damage around the syrinx 7 Adams RD, Victor M, Ropper AH. Syringomyelia. In: reaches the lateral horn, it will segmentally Adams RD, Victor M, Ropper AH, eds. Principles of neurol- aVect the SPGNs or adjacent structures.14 This ogy. 6th ed. New York: McGraw-Hill, 1997;1269–77. 8 Finlayson AI. Syringomyelia and related conditions. In: on September 24, 2021 by guest. Protected copyright. time our results have shown, from the view- Joynt RJ, eds. Clinical neurology. Philadelphia: Lippincott- Raven, 1995;1–17. point of sweating, that there evidently is a 9 Döring G. Zur Klinik vegetativer Störungen bei Syringomy- hyperactivity of the SPGNs as long as the dis- elie und über trophische Störungen im allgemeinen. Dtsch Med Wochenschr 1949;74:754–9. ability is mild; however, as the disability 10 Stovner LJ, Sjaastad O. Segmental hyperhidrosis in two sib- progresses, the hyperactivity gradually de- lings with Chiari type I malformation. Eur Neurol 1995;35: 149–55. creases and is replaced by hypoactivity (table). 11 Johnson RH, Lambie DG, Spalding JMK. Syringomyelia We have a choice of two possibilities for the and related conditions. In: Joynt RJ, ed. Clinical neurology. Philadelphia: Lippincott-Raven, 1995:1–17. mechanism responsible for the hyperactivity of 12 Pryse-Phillips W. Companion to clinical neurology. In: the SPGNs so far; the first is that the SPGNs Pryse-Phillips W, eds. Boston: Little, Brown, 1995;812. 13 Milstein JM, Cohen ME, Sinks LF. The influence and reli- are stimulated directly by a minimal tissue ability of neurologic assessment and Karnofsky perform- damage; the second is damage to the ILINs10 ance score on prognosis. Cancer 1985;56:1834–6. 14 Sudou K, Tashiro K. Segmental hyperhidrosis in syringomy- (preceding the damage to the SPGNs)—we elia with Chiari malformation. J Neurol 1993;240:75–8. have recently acquired some knowledge of 15 Berry MM, Standring SM, Bannister LH. Autonomic nerv- 15 16 ous system. In: Williams PL, ed. Gray’s anatomy. 38th ed. these ILINs. In either case, as the disease New York: Churchill Livingstone, 1995:1292–312. progresses, hyperactivity will shift to normoac- 16 Lewis DI, Coote JH. Chemical mediators of spinal tivity and finally to hypoactivity because of inhibition of rat sympathetic neurones on stimulation in the nucleus tractus solitarii. J Physiol (London) 1995;486:483– progressive and irreversible damage to the 94. J Neurol Neurosurg Psychiatry 1999;67:549–559 549

Hz-2.5 Hz with some mild increase in bilateral Despite its undoubted value in many indi- slow activity and no convincing evidence of vidual cases of temporal lobe , the LETTERS TO electrographic focalisation. Video EEG moni- IAP has remained a controversial assessment toring showed apparent generalised instrument.5 Amid this controversy its poten- THE EDITOR without any focal onset on scalp EEG. Brain tial usefulness in other patient groups seems MRI disclosed a well defined atrophic lesion to have been overlooked. A primary criticism involving the left frontal pole considered likely of its use in temporal lobe epilepsy has been to be post-traumatic in origin. Interictal FDG the question of irrigation and whether the Behavioural status during the PET and HMPO SPECT disclosed hypoper- medial temporal lobe is adequately “disa- intracarotid amobarbital procedure fusion in the left anterior frontal region bled” during the procedure. This particular limitation is not applicable when used in the (Wada test): relevance for surgical commensurate with the abnormality shown on patient with frontal lobe epilepsy, as the ( MRI. Although his electroclinical pattern was management J Neurol Neurosurg Psychiatry region of interest is clearly ablated via supply 1999;67:549–559) suggestive of symptomatic generalised epi- lepsy, because of the left frontal lesion, from the carotid arterial system. Caution Presurgical evaluation in many epilepsy onset from that region was considered likely. must, however, be exercised with respect to programmes often includes the intracarotid On neuropsychological examination, his possible crossflow into the contralateral ante- amobarbital procedure (IAP). Sodium general cognitive function was normal. At a rior cerebral artery via the anterior communi- amytal is injected into the internal carotid behavioural level, however, he presented as cating artery. When such crossflow is present, artery to produce a temporary “pharmaco- very peurile in manner with a very rigid, the ability to assess validly the integrity of logical paralysis” of hemispheric function. inflexible cognitive style. The neuropsycho- contralateral frontal lobe function will be Traditionally, the IAP has been employed in logical opinion was of a mild frontal lobe syn- confounded by virtue of a pharmacologically patients with refractory temporal lobe epi- drome consistent with the history of trau- induced bilateral frontal lobe syndrome. As lepsy being considered for anterior temporal matic head . There was no current with the use in cases of temporal lobe lobectomy. In these cases it is used to evidence of psychiatric disorder. Although epilepsy, only a restricted form of assessment determine cerebral dominance for language,1 having successfully passed his final year of is possible with the frontal lobe patient during to assess the risk of severe postsurgical secondary school (together with several the period of ablation. An assessment focus- amnesia,2 and to predict postsurgical material courses of advanced education), he had ing on issues of behavioural regulation would specific memory changes.3 More recently, the remained unemployed due to his seizures. He seem most useful. use of the IAP has been extended to compli- was socially isolated and his interpersonal It should be borne in mind that the degree ment EEG localisation and radiological data relationships were limited. of frontal lobe dysfunction induced by the by lateralising temporal lobe dysfunction.4 He had severe life threatening epilepsy with IAP represents the “worst case scenario” as The IAP may have a hitherto unrecognised the surgical option the only remaining avenue the entire frontal lobe is included in the abla- role in patients with refractory frontal lobe of treatment. However, as surgical manage- tion. There are likely to be few surgical epilepsy being considered for frontal lobec- ment would involve resection of the left fron- scenarios in which a comparable extensive resection of tissue is likely to be considered, tomy. Specifically, observation of behavioural tal lobe against a background of traumatic and results must be interpreted in this function during the period of the ablation head injury and the possibility of more gener- context. This limitation not withstanding, the may provide useful information about the alised frontal lobe compromise, a left hemi- IAP does seem to have a role in separating out integrity of the contralateral frontal lobe. spheric IAP was performed. Sodium amytal those patients in whom more extensive fron- This is particularly relevant in those candi- (125 mg) was administered via a slow hand tal lobe resections could be considered as dates with a history of cerebral trauma in injection. Of relevance, no crossflow into the opposed to those in whom a more conserva- whom damage to the bifrontal lobe is known contralateral anterior cerebral artery via the tive approach is warranted. or suspected. A review of the IAP studies anterior communicating artery was present This case report forms only the basis for a performed on patients with temporal lobe (as assessed by a separate injection of contrast novel hypothesis that clearly requires more epilepsy in our comprehensive epilepsy pro- medium). The injection was accompanied by rigorous scientific research before its clinical gramme (1991–8) suggests that the emer- a dense right hemiplegia and global aphasic utility can be reliably established. Nonethe- gence of frontal lobe behavioural features is arrest. Resolution of language was character- less, we think that it is worth drawing the common in patients in whom the aetiology ised by a dense perseveration of counting attention of the epileptological community to leads to the suspicion of bifrontal compro- which could not be influenced by the the potential application of the IAP in the mise (for example, a history of traumatic examiner. Despite normal comprehension, he surgical management of extratemporal cases. head injury). By contrast, these features showed severely impaired capacity for motor rarely emerge in cases of non-traumatic aeti- regulation (go-no go paradigm), together MARIE F O’SHEA ology, in which the integrity of frontal lobe with marked behavioural disinhibition (agita- MICHAEL M SALING systems is presumed. Although it remains an tion, swearing, verbosity, childishness). Al- Department of Neuropsychology incidental finding in the context of determin- though seemingly aware of some aspects of SAMUEL F BERKOVIC ing the suitability of a candidate for anterior his behaviour (apologising for swearing), he Department of Neurology, Austin and Repatriation temporal lobectomy, this outcome may have seemed unable to modify his responses. The Medical Centre, Melbourne, Australia; and potential implications for the selection of overall impression was of a pronounced fron- Department of Medicine, University of Melbourne, patients for frontal lobectomy. tal lobe syndrome, suggesting that the right Grattan Street, Parkville 3052, Australia. We report a case of frontal lobe epilepsy sec- frontal lobe had incurred some damage Correspondence to: Dr Marie F O’Shea, Depart- ondary to a traumatic head injury. Out of con- secondary to the documented head trauma ment of Neuropsychology, Austin and Repatriation cern for untoward postoperative behavioural and that he must have been reliant on some Medical Centre (Austin Campus), Studley Road, Heidelberg, Victoria 3084, Australia. Telephone change, we employed the IAP in an attempt to left frontal contribution. 613 3 03 9496 5913; Fax 613 3 03 9457 2654. predict the risk of a frontal lobe syndrome. On the basis of the IAP findings, a selective A 39 year old man had a 23 year history of cortical resection (as opposed to more exten- 1 Wada J, Rasmussen T. Intracarotid injection of severe refractory epilepsy. The seizures post- sive frontal lobectomy) restricted to the region sodium amytal for the lateralization of cerebral speech dominance: experimental and clinical dated a motor car accident at the age of 12 of damage was advised. Intraoperative electro- observations. J Neurosurg 1960;17:266–82. years when he sustained a head injury with an corticography showed active focal epileptiform 2 Rausch R, Silfveius H, Weiser H-G, et al. ill defined period of loss of consciousness. Sei- discharges maximal in the inferior frontal lobe Intraarterial amobarbital procedures. In: Engel J, ed, Surgical treatment of the . 2nd ed. zures commenced within months of that injury in the electrodes closest to the lesion. A corti- New York: Raven Press, 1993:341–57. and, although initially well controlled, became cal resection was performed with frameless 3 Kneebone AC, Chelune GJ, Dinner DS, et al. refractory within a few years. The seizure types stereotaxy guidance excision of the frontal Intracarotid amobarbital procedure as a pre- included staring spells, violent tonic-clonic lesion. Histopathology on the resected tissue dictor of material-specific memory change after anterior temporal lobectomy. Epilepsia 1995; seizures, and atonic drop attacks. He had com- showed an old post-traumatic cyst involving 36:857–65. plications from his epilepsy including a frac- the cortex and white matter. His postoperative 4 Baxendale SA, Van Paesschen W,Thompson PJ, tured jaw, two episodes of severe burning due course was unremarkable. When reviewed 3 et al. The relation between quantitative MRI months after surgery he was seizure free. His measures of hippocampal structure and the to seizures while showering, multiple episodes intracarotid amobarbital procedure. Epilepsia of postictal confusion and probable postictal performance on neuropsychological evalua- 1997;38:998–1007. psychosis, a lung abscess secondary to aspira- tion remained commensurate with presurgical 5 Jones-Gotman M, Barr WB, Dodrill CB, et al. tion, and episodes of . Interic- status. There were no novel subjective com- Controversies concerning the use of intraarte- rial procedures. In: Engel J, ed. Surgical tal EEG recordings showed bilateral general- plaints. Mood, behaviour, and temperament treatment of the epilepsies. 2nd ed. New York: ised spike and wave discharges at around 2 remained stable. Raven Press, 1993:445–9. 550 Letters, Correspondence, Book reviews, Correction

Reversal of tetrabenazine induced WOLFGANG SCHREIBER hemiparesis and the diVerent temperature depression by selective noradrenaline JÜRGEN-CHRISTIAN KRIEG sensation in the limbs resolved completely Department of Psychiatry and Psychotherapy, (norepinephrine) reuptake inhibition within 3 weeks. Philipps-University, Rudolf-Bultmann-Straâe8, Tibial nerve somatosensory evoked poten- D-35033 Marburg/Lahn, Germany tials (SSEPs) had regular N22 and P40 Tetrabenazine (TBZ), a synthetic benzoqui- TOBIAS EICHHORN latencies and amplitudes. Central motor con- nolizine, was first introduced as a neuroleptic Department of Neurology, Philipps-University, duction time (CMCT) after transcranial agent in 1960, and is now widely used in the Rudolf-Bultmann-Straâe 8, D-35033 Marburg/Lahn, magnetic stimulation was prolonged to the treatment of hyperkinetic movement disor- Germany right abductor digiti minimi (9.2 ms) and ders such as , tics, or tardive dyski- Correspondence to: Dr Wolfgang Schreiber, De- tibialis anterior (23.1 ms). The CMCT to the nesia. The side eVect profile is mainly partment of Psychiatry and Psychotherapy, left target muscles was normal. Duplex Philipps-University, Rudolf-Bultmann-Stra e8, characterised by the triad of drowsiness/ â sonography showed increased flow velocity fatigue, , and depression; de- D-35033 Marburg/Lahn, Germany. Telephone 0049 6421 286277; fax 0049 6421 285229; email on the level of the cervical vertebrae 3 to 5 pression is found in about 15% of patients [email protected] with a maximum of 214 cm/s in the right and treated with TBZ.1 We here report on the 197 cm/s in the left vertebral artery. Colour rapid reversal of depressive symptoms in a 1 Jankovic J, Beach J. Long-term eVects of mode showed irregular narrowings of the patient treated with TBZ for orofacial dysto- tetrabenazine in hyperkinetic movement disor- lumen indicating dissections. nia by administering the new and highly ders. Neurology 1997;48:358–62. Cervical MRI showed a spinal cord infarc- selective noradrenaline (norepinephrine) re- 2 Montgomery S. Reboxetine: additional benefits tion at the level C2 (figure). The circumfer- 2 to the depressed patient. J Psychopharmacol uptake inhibitor (SNRI) reboxetine. 1997;11(suppl 4):S9–15. ence and dorsal part of the cord were not On admission, the 64 year old woman pre- 3 Erickson JD, Schäfer MK, Bonner TI, et al. Dis- aVected. In digital subtraction angiography sented with perioral and lingual hyperkinesias tinct pharmacological properties and distribu- (DSA) both vertebral arteries had string signs tion in neurons and endocrine cells of two iso- as well as intermittent and involuntary move- forms of the human vesicular monoamine in the V1 and V2 segments with collateral flow ments of her lower jaw, which had lasted for transporter. Proc Natl Acad Sci U S A 1996;93: to the distal V2–4 segments via the thyreocer- about 2 years, causing her a considerable 5166–71. vical trunk (cervical ascendent artery) and the 4HoVman BJ, Hansson SR, Mezey E, et al. impairment of articulation. No history of Localization and dynamic regulation of bio- costocervical trunk also. The anterior spinal neuroleptic treatment or Parkinson’s disease genic amine transporters in the mammalian artery was incompletely contrasted by unilat- was evident. Her cranial CT and blood central nervous system. Front Neuroendocrinol eral spinal branches of the right vertebral chemistry were normal. We diagnosed a seg- 1998;19:187–231. artery. They originated at the level of dissec- 5 Knoll J, Miklya I, Knoll B, et al. Phenylethyl- mental , which improved dramati- amine and tyramine are mixed-acting sym- tion. The intradural origins of the anterior spi- cally after initiation of a tetrabenazine pathomimetic amines in the brain. Life Sci nal artery from the distal part of the vertebral medication (60 mg a day). This successful 1996;58:2101–14. arteries (V4 segment) were not visible. treatment response, however, was accompa- Bilateral spontaneous VAD is not rare, but often missed. In most cases, microtrauma pre- nied by a severe depressive syndrome, which Spinal sulcal artery syndrome due to was characterised by a mixed anxious- ceding the dissection can be recalled by the spontaneous bilateral vertebral artery depressive mood, low self esteem, a complete patients. Due to the mild mechanical impact, loss of drive, and intermittent suicidal dissection the action of predisposing factors might be ideations. After switching from TBZ to postulated. Among these may be changing in In young adults vertebral artery dissection tiapride, the patient recovered from depres- type III collagen, , fibromuscular dys- (VAD) is an important cause of brain sion, but her neurological status worsened 12 plasia, infections in the near past, and inflam- infarction. A known mechanism is micro- 2 significantly. The re-exposure to TBZ again matory vasculopathy. Magnetic resonance traumata due to abrupt head movements— ameliorated hyperkinesia, but provoked a imaging with typical semilunar mural hae- for example, chiropractic manoeuvres. In depressive relapse. A comedication with matoma and in addition magnetic resonance addition a pathogenetic role of connective tis- angiography (MRA) with complementary reboxetine (6 mg/day), a new and selective sue diseases, cystic media necrosis, fibromus- noradrenaline reuptake inhibitor, finally led documentation of an irregular lumen or taper- cular dysplasia, migraine, and inflammatory ing occlusion have a high sensitivity and to a stable remission of the depressive symp- diseases has been postulated.3 In VAD initial toms within a week, without any worsening of specificity in cases of internal carotid artery neck pain is often reported, which may be dissection.1 By contrast, mural haematomas of the dystonic syndrome. slight. Lesions caused by VAD are cerebellar Tetrabenanzine (TBZ) is known to act as a the VA especially in the V1 and the V3 or infarcts, unilateral or bilateral segments are often not detectable by MRI. In monoamine depleting and dopamine recep- thalamic infarcts (top of the basilar syn- tor blocking drug.1 In more detail, TBZ cases of unclear non-invasive findings, DSA is drome), or infarctions in the posterior cer- still the method of choice.1 binds to and inhibits specifically the human ebral artery territory due to intra-arterial vesicular monoamine transporter isoform 2 In addition to consecutive brain infarc- embolism or haemodynamic decompensation tions, cervical spinal cord infarctions and (hVMAT2). Whereas the indolamine serot- when collaterals are insuYcient.1 Lesions of onin (5-HT) performs a similar aYnity for nerve root compression syndromes may the cervical spinal cord are rare because of its occur in cases of unilateral or bilateral VAD. both hVMAT1 and hVMAT2, catecho- 45 good collateral supply. We report on a Probably as a result of the pial collateral net- lamines such as noradrenaline exhibit a patient with a syndrome of the spinal sulcal 3 work and the dual posterior spinal artery, spi- threefold higher aYnity for hVMAT2. As artery (incomplete Brown-Séquard syn- these specific transporters are responsible for drome) caused by spontaneous bilateral VAD. packaging monoamine neurotransmitters A 43 year old man with a history of arterial into presynaptic secretory vesicles for release hypertension presented with left sided numb- by exocytosis, the inhibition of hVMAT2 by ness sparing the face, which had evolved sud- compounds such as tetrabenazine thus denly while he was walking. In addition, he results in consecutive noradrenaline reported on dull right sided neck pain irradi- depletion.4 ating into the occiput, which had been Alterations of noradrenergic neurotrans- initiated by a head rotation while he was mission—that is, a neuronal noradrenaline working at a computer 2 weeks before. The depletion—can therefore be postulated to neck pain had spontaneously ceased 6 days form one major origin of TBZ induced later. Neurological examination disclosed depression. In line with this assumption, dissociated sensation defect on the left with brain-specific catecholaminergic activity en- an indistinct level around C4 to C6. Below hancers (CAEs) such as phenylethylamine this level on the left he had a marked have been shown to antagonise TBZ induced hypalgesia and nearly a loss of temperature depression-like behaviour in rats.5 Modulat- sense. The right limbs were warmer than the ing this altered noradrenergic neurotransmis- left ones. In addition, we found mild right sion pattern by the administration of selective sided motor system deficits. Cranial nerve noradrenaline reuptake inhibitors such as function was intact, despite a right sided reboxetine may thus provide a new, specific, Horner’s syndrome. According to chest and fast acting tool in the management of radiography phrenic nerve function was depression caused by TBZ and related (neu- preserved. Routine laboratory findings in- Coronal T2 weighted MRI: ventrolateral roleptic) compounds. cluding CSF analysis were normal. The paramedian right sided medullary infarction. Letters, Correspondence, Book reviews, Correction 551 nal cord infarction is often located in the American descent with a strong founder south east (CVE28), and north east (CVE29). anterior spinal artery territory with the grey eVect.23 Around 50% of non-Hispano- Seventy seven subjects including 55 potentially matter of the anterior horns exhibiting the American families showed linkage to CCM1 informative meioses and 12 spouses gave their highest vulnerability to ischaemia.45 This but no common haplotype was found.45 A informed consent. They were examined by a mechanism may lead to a typical “snake eye” recent study showed linkage of cerebral board certified neurologist, underwent cer- configuration of medullary infarction.3 Be- cavernous malformations to two additional ebral MRI, and blood samples were taken. sides the supply via VA spinal branches, loci.5 No Spanish family with cerebral Magnetic resonance imaging was used to which is found in 19% only unilaterally,4 cavernous malformations has been analysed establish status for linkage analysis. Thirty four there are branches originating from the so far. members had MRI diagnosis of cavernomas ascendant cervical artery (thyreocervical We report herein a genetic linkage analysis and were considered as aVected. Among them, trunk) and the costocervical trunk supplying conducted on nine Spanish families with 14 experienced neurological symptoms (cer- the spinal cord. cerebral cavernous malformations. All proce- ebral haemorrhage n=6, seizures n=8). Nine- DSA findings in the present case suggest dures were approved by an ethics comittee. teen members with normal cerebral MRI were that spinal branches originating from the The families were unrelated and originated considered as healthy. Twelve members with- right V2 segment were dominant feeders of from diVerent regions of Spain (south west out MRI investigation had an unknown status. the anterior spinal artery whereas there was (CVE2, 3, 4, 10, 17, 25), central (CVE24), Analysis of pedigrees was consistent with an no evidence of direct communication be- tween vertebral and spinal arteries from the V4 segment. The dissection involved the V2 A CVE2 CVE3 ? ? segment from which these spinal branches ? originate. A transient occlusion of these spinal branches is a likely consequence. This ? unusual type of arterial medullary supply ? ? may explain why VAD causes spinal cord inf- arction. Contrary to Pullicino,5 who de- ? ? scribed upper limb atrophies due to cervical ? ? ? spinal cord infarction involving the anterior horns, the present case shows a unilateral CVE4 ? ? CVE10 involvement of commissural, spinothalamic, pyramidal, and vasoconstrictor tracts. To our ? ? knowledge sulcal spinal artery syndrome caused by bilateral spontaneous VAD has not yet been described. In conclusion, differential diagnosis of acute spinal symptoms in young adults should include spontaneous unilateral or bilateral VAD with cervical spinal cord ischaemia. CVE17 CVE24 CVE25 S WEIDAUER ? ? D CLAUS Department of Neurology ? M GARTENSCHLÄGER Institute for Radiology, Klinikum Darmstadt, ? ? Teaching Hospital University Frankfurt, Germany CVE28 Correspondence to: Professor D Claus, Depart- CVE29 ment of Neurology, Klinikum Darmstadt, Teaching ? ? ? Hospital University Frankfurt, Heidelberger Land- ? ? strasse 379, 64297 Darmstadt, Germany.

1 Auer AS, Felber S, Schmidauer C, et al. ?? ? Magnetic resonance angiographic and clinical features of extracranial vertebral artery dissec- tion. J Neurol Neurosurg Psychiatry 1998;64:474–81. 2 Caplan LR, Zarins CK, Hemmati M. Spontane- B Hispanic- ous dissection of the extracranial vertebral Marker CVE2 CVE3 CVE4 CVE10 CVE24 CVE25 CVE28 CVE17 CVE29 arteries. 1985;16:1030–8. American 3 Hundsberger T, Thömke F, Hopf HC, et al. Symmetrical infarction of the spinal cord due D7S2410279 273 265 269 265 265 267 263 265 263263 269 to spontaneous bilateral vertebral artery dissec- tion. Stroke 1998;29:1742. 4 Kaneki M, Inoue K, Shimizu T, et al. Infarction D7S2409ND 221 219 215 221 219 219 223 219 223223 219 of the unilateral horn and the lateral column of the spinal cord with sparing of posterior D7S1813137 123 127 127 127 125 127 131 125 127127 127 columns: demonstration by MRI. J Neurol Neurosurg Psychiatry 1994;57:629–31. 5 Pullicino P. Bilateral distal upper limb amyotro- D7S1789137 139 133 133 129 131 133 129 129 133129 133 phy and watershed infarcts from vertebral dissection. Stroke 1994;25:1870–2. MS65BND 135 133 131 133 135 133 129 ND ND137 133

Spanish families with cavernous D7S646185 185 185 187 197 183 185 181 187 197 201197 185 angiomas do not share the Hispano- American CCM1 haplotype D7S558107 107 107 103 107 103 103 103 103 103103 103

Cerebral cavernous malformations are vascu- D7S689129 127 125 129 127 127 139 127 125 127129 127 lar malformations mostly located in the CNS. Their frequency is estimated close to 0.5% in (A) Pedigrees of the nine families with cerebral cavernous malformations. Black symbols=symptomatic the general population.1 Cerebral cavernous patients with cavernous angiomas on MRI; half filled symbols=asymptomatic members with cavernous malformations occur as a sporadic or heredi- angiomas on MRI; empty symbols=asymptomatic members with normal MRI; question tary condition. From the Hispano-American mark=members with unknown status. (B) Comparison of the Hispano-American CCM1 haplotype population, familial forms were reported with and the haplotypes segregating with the disease phenotype within Spanish families. Polymorphic 2 markers are shown on the left. Numbers indicate the sizes in base pairs. Primers used to amplify a high frequency. CCM1, a hitherto uniden- D7S2409 were diVerent from those in the Hispano-American families resulting in a diVerent size of tified gene mapping on chromosome 7 was the amplified fragment. M65B was not studied in the Hispano-American families. Family CVE24 shown to be involved in all families with cer- was not informative for D7S646. For families CVE17 and CVE29, the two haplotypes of the aVected ebral cavernous malformations of Hispano- siblings are indicated. ND=not determined. 552 Letters, Correspondence, Book reviews, Correction autosomal dominant pattern of inheritance cerebral cavernous malformations, this hap- rosurgical procedure. In performing third (figure A). lotype is most likely not predominant in ventriculostomy, a hole is created in the floor Eight polymorphic microsatellite markers Spain, and the strong founder eVect seen in of the third ventricle, allowing CSF inside the spanning the CCM1 interval were selected for all published Hispano-American families ventricle to drain out to the CSF space linkage analysis. Four were chosen from the with cerebral cavernous malformations might surrounding the brain. Although third ven- Généthon linkage map (D7S2410, D7S2409, be specific for this population. triculostomy has a low operative morbidity D7S646, D7S689), and three from the and a high probability of success in secondary Cooperative Human Linkage Center HJ is supported by the Schweizerische Stiftung für , it is only commonly used on (D7S1813, D7S1789, D7S558). The last one medizinisch-biologische Stipendien (Switzerland), patients with aqueductal stenosis and the (M65B) was identified by SL based on SL by the Fonds de Recherche en Santé (Canada), pediatric population. To avoid placing shunts PL by the Collège des Enseignants de Neurologie sequencing data of a bacterial artificial chro- and ZENECA pharmaceutical group. The work was in patients with inoperable metastatic brain mosome (Genbank HSAC000065; BAC founded by INSERM, Ministère de l’Enseignement tumours who typically have only a few RG085C05). The length of the genetic inter- Superieur et de la Recherche, CSIC, and the Fondo months to live, we have oVered the patients val flanked by markers D7S2410 and de Investigacion de la Seguridad Social (Fiss: third ventriculostomy as a palliative proce- 99/0407). D7S689 is 4 centimorgans (cM). Marker dis- dure. tances between D7S2410/D7S2409, HHJUNG We performed third ventriculostomy on D7S1813/D7S1789/D7S646/D7S558, and P LABAUGE seven patients with hydrocephalus due to S LABERGE D7S689 have been estimated to be 2.2 cM, E MARÉCHAL metastatic tumours of the posterior fossa or 3 and 1.8 cM, respectively. Oligonucleotide E TOURNIER-LASSERVE thalamus. They typically presented with sequences are available through the Genome INSERM U25, Faculté de Médecine Necker, Paris, symptoms of acute hydrocephalus in addition Data Bank (John Hopkins University, Balti- France to any local mass eVect of the tumour. more). Genotyping and linkage analysis M LUCAS Postoperatively, five patients were relieved of (LINKAGE package version 5.1) were per- Laboratorio de Biologia Molecular hydrocephalic symptoms and follow up brain formed as previously described.5 imaging studies disclosed decreased ventricu- J M GARCIA-MORENO Lod scores were calculated in the five M A GAMERO lar size. These five patients had a median families having a suYcient number of poten- G IZQUIERDO hospital time of 6.5 days and median survival tially informative meioses—that is, CVE3 Servicio de Neurologia, Hospital Unversitario Virgen of 9.5 weeks after the operation (table). Their (eight), CVE4 (16), CVE10 (seven), CVE25 Macarena, Avenida Dr Fedriani, 41071 Sevilla, Spain hospital stay was prolonged by care of their (five), and CVE28 (seven). Lod scores higher E TOURNIER-LASSERVE primary disease. However, most of our than 1 were obtained for three families Hôpital Lariboisière, Paris, France patients who underwent this operation for hydrocephalus caused by other diseases were (CVE3, 4, and 28) for at least one marker. Correspondence to: E Tournier-Lasserve, Due to incomplete informativity of three INSERM U25, Faculté de Médecine Necker, 156 discharged from the hospital between 24 and markers within family CVE4, lod scores did Rue de Vaugirard, 75730 Paris Cedex 15. France, 48 hours from the procedure. There were no not reach the level of 3. In family CVE10, lod Telephone 0033 1 45 67 25 97; fax 0033 1 40 56 01 operative complications. All five patients had scores were close to 1 for four markers 07; email: [email protected] no evidence of redevelopment of hydrocepha- (D7S2410, D7S1789, D7S558, D7S689). lus up to the last clinic visit. Family CVE25 showed a lod score close to 0 1 Otten P, Pizzolato GP, Rilliet B, et al. A propos Two patients had unsuccessful results from for all markers. In this family, two aVected de 131 cas d’angiomes caverneux (cavern- their third ventriculostomy. One patient (case and one asymptomatic sibling with normal omes) du SNC, repérés par l’analyse rétrospec- 4) showed no change from his initial tive de 24 535 autopsies. Neurochirurgie standard MRI inherited the same haplotype 1989;35:82–3. neurological exam after the procedure, but from their aVected father. When the data of 2 Günel M, Awad IA, Finberg K, et al. A founder his mental status deteriorated on post opera- all examined families were pooled, a maxi- mutation as a cause of cerebral cavernous mal- tive day 6. Brain CT showed no change in the mum combined lod score of 5.92 was formation in hispanic Americans. N Engl J Med size of his ventricles compared with the scan 1996;334:946–51. obtained for marker D7S2410 at è=0. 3 Johnson EW, Lyer LM, Rich SS, et al. Refined obtained on the day of admission. The In seven families (CVE2, 3, 4, 10, 24, 25, localization of the cerebral cavernous malfor- patient’s family requested comfort care only and 28), all aVected members inherited an mation gene (CCM1) to a 4-cM interval of and the patient died 2 days later. In the chromosome 7q contained in a well-defined haplotype that was not shared by their healthy YAC Contig. Genome Res 1995;5:368–80. second case (case 6) the patient had improve- relatives (figure B). In family CVE17, both 4 Labauge P, Laberge S, Brunereau L, et al. ment in his neurological examination and aVected siblings inherited a distinct haplo- Hereditary cerebral cavernous angiomas: clini- ventricle size by CT scan immediately after cal and genetic features in 57 French families. the operation, but had recurrent symptoms of type from their aVected mother. Although the Lancet 1998;352:1892–7. limited size of this family does not allow to 5 Craig HD, Günel M, Cepeda O, et al. Multilo- hydrocephalus 11 days later. After placement formally conclude, this suggests genetic cus linkage identifies two new loci for a of a ventriculoperitoneal shunt, his examina- heterogeneity. In family CVE29, the two Mendelian form of stroke, cerebral cavernous tion returned to baseline. malformation, at 7p15–13 and 3q25.2–27. aVected siblings inherited the same haplo- Hum Mol Gen 1998;7:1851–8. Every patient except the person described types from their mother and father whose in pase 4 received brain radiation therapy status was unknown. after the palliative procedure. One patient None of the families shared a common hap- Hydrocephalus caused by metastatic (case 3) underwent a course of radiation lotype (figure B). In addition, the extended brain lesions: treatment by third treatment prior to the operation. Another Hispano-American haplotype was not segre- ventriculostomy (case 5) had radiation to her orbit in the dis- gating with the disease phenotype in any of the tant past after enucleation for retinoblast- nine families including the four families with Metastasis to the brain occurs in 20%–40% oma. Even though previous radiotherapy may suggested linkage to CCM1. However, two out of cancer patients.1 About 20% of these be considered a contraindication for third of nine families (CVE2 and 3), the D7S646 metastases are located in the posterior fossa, ventriculostomy by some authors, it did not (185bp) and D7S558 (107bp) alleles segregat- cerebellum, and brainstem. Metastatic dis- seem to aVect the success of third ventricu- ing with the disease phenotype were identical ease to periventricular brain tissue can lostomy in our patients. Carcinomatous men- to the ones observed in the Hispano-American obstruct the flow of cerebrospinal fluid (CSF) ingitis which could have caused a concomi- haplotype. Consequently, we analysed the fre- produced in the ventricles to the subarach- tant communicating hydrocephalus was not quency of this combination of alleles within a noid space where it is normally absorbed by grossly evident on examination, on any of the panel of 80 haplotypes of 40 healthy white arachnoid granulations. This typically causes brain imagings, or during endoscopy. How- subjects. Frequency was 17% compared with an obstructive or non-communication hydro- ever, tumours in contact with CSF space can 22% in our Spanish sample. Therefore, this cephalus. A shunt has been customarily also cause a communicating hydrocephalus finding might be attributed to a random distri- placed to drain CSF from a lateral ventricle by raising CSF protein which can obstruct bution of these alleles. through a pressure regulating valve and into distal CSF space and arachnoid granulations. In conclusion, linkage analysis of Spanish the atrium or peritoneal or pleural cavity. Our success rate of about 70% (five of families with cerebral cavernous malforma- Even though this technique has been success- seven) for third ventriculostomy in periven- tions did not show any evidence for Hispano- ful in relieving the hydrocephalus, it has tricular metastatic disease is consistent with American haplotype sharing or a founder about a 50% chance of infection or failure the results obtained with third ventriculos- eVect. Although our sample was limited in from blockage.2 tomy for adult patients with secondary size and does therefore not formally exclude Another option for the treatment of hydrocephalus.3 This is comparable with the the presence of the Hispano-American haplo- obstructive hydrocephalus is third ventricu- alternative shunting with an implanted cath- type in additional Spanish families with lostomy, a minimal invasive endoscopic neu- eter which has a first year revision rate as high Letters, Correspondence, Book reviews, Correction 553

Table 1 Clinical characteristics of patients who underwent third ventriculostomy for obstructive hydrocephalus

Case Age (y), Postoperative stay in Survival time No Sex Diagnosis Result* hospital(days) (weeks) 1 70,M Lung mixed adenocarcinoma and squamous cancer metastasis to thalamus Improved 17 4 2 46,F Ovarian adenocarcinoma metastases to cerebrum and medulla Improved 9 13 3 38,F Breast ductal carcinoma metastases to brainstem and cerebellum Improved 3 8 4 75,M Rectal adenocarcinoma metastasis to cerebellum Failed 8 1 5 39,F Breast adenocarcinoma metastasis to cerebellum Improved 4 11 6 60,M Lung adenocarcinoma metastasis to thalamus Failed 6 6+† 7 64,M Oesophageal carcinoma metastatic to cerebellum Improved 7+ 1+†

*Results are considered improved if the patient had resolution of symptoms and follow up imaging showed hydrocephalus improved or resolved. †Patient is currently alive. as 50%, with the highest failure rate in the Such an interaction between cortical blood tumour during neuronal activation, suggest- first few months after shunt placement.2 The flow and tumour blood flow may be of value ing that the local blood flow of the tumour complication rates for both procedures are for evaluating mechanisms of neurological was decreased by a transient increase of rCBF low. Third ventriculostomy and shunting can symptoms associated with brain tumours. induced by neuronal activation. potentially cause a stroke, bleeding, ventricu- Neuronal activation causes an increase of The patient was a 35 year old right handed litis, , a subdural haematoma, CSF regional cerebral blood flow (rCBF) in the man who presented with complaints of head- leak, diabetes insipidus, and SIADH. How- activating cortical area.2 Near infrared spec- ache and dizziness. A neurological examina- ever shunting has additional risks of mechani- troscopy (NIRS) demonstrates the increase tion showed no abnormalities and a decline in cal malfunction, complications associated in rCBF during neuronal activity as increases language functions. A postcontrast CT with implanting a foreign body, and overd- in oxygenated haemoglobin (oxy-Hb) and showed a well defined large enhancing rainage syndrome.4 total haemoglobin (total-Hb) with a decrease tumour (4×5 cm) compressing the left frontal Because third ventriculostomy restores in deoxyhaemoglobin (deoxy-Hb)3–5; NIRS is lobe. Computed tomographic angiography near normal CSF dynamics,5 overdrainage is an optical method to measure concentration showed that the branches of the left middle prevented. The procedure is also minimally changes of oxy-Hb, deoxy-Hb, and total-Hb cerebral artery supplied the tumour (figure invasive and safe. The procedure’s low (oxy-Hb+deoxy-Hb) in cerebral vessels by A). The patient underwent a left frontal morbidity, high eYcacy, and potentially short means of the characteristic absorption spec- craniotomy for removal of the tumour; the hospital stay are well suited as a palliative tra of haemoglobin in the near infrared range. pathological diagnosis was meningioma. The treatment of hydrocephalus for patients with In the present study, we measured changes NIRS measurement was performed before an expected shortened life span. We propose of oxygenation and haemodynamics in the the operation. that third ventriculostomy should be oVered brain tumour adjacent to the activating We measured haemodynamic changes in as a first treatment to patients suVering from cortex by means of NIRS. We found transient the brain tumour during neuronal activation obstructive hydrocephalus from unresectable decreases in oxy-Hb and total-Hb in the in the left frontal lobe induced by cognitive tumours.

TIEN T NGUYEN A (A) CT angiography of the brain MARK V SMITH tumour. Note that the tumour was GERARD S RODZIEWICZ supplied by the branches of the left Department of Neurosurgery middle cerebral artery. (B) SHEILA M LEMKE Oxygenation changes in the brain Department of Medicine, Division of Oncology, SUNY tumour during the naming task Health Science Center, University Hospital, Syracuse, measured by NIRS. The ordinates New York, USA indicate concentration changes of Correspondence to: Dr G S Rodziewicz, Depart- oxy-Hb, deoxy-Hb, and total-Hb in ment of Neurosurgery, 750 East Adam Street, Syra- arbitrary units (au). Horizontal thick cuse, NY 13210, USA. Telephone 001 315 464 bar indicates the period of the task. 4470;fax 001 315 464 5520;email [email protected]

1 Patchell RA. Brain metastases and carcinoma- tous meningitis. In: AbeloV MD, Armitage JO, Lichter AS, et al,eds. Clincal oncology. New York: Churchill Livingstone, 1995:629–41. 2 Borgbjerg BM, Gjerris F, Albeck MJ, et al. Fre- 1 quency and causes of shunt revision in different B cerebrospinal fluid shunt types. Acta Neurochir (Wien) 1995;136:189–94. Oxy-Hb 3 Jones RFC, Kwok BCT, Stening WA, et al. The current status of endoscopic third ventriculos- Deoxy-Hb tomy in the managment of non- Total-Hb communicating hydrocephalus. Minim Invasive Neurosurg 1994;37:28–36. 0 4 Faulhauer K, Schmitz P.Overdrainage phenom- ena in shunt treated hydrocephalus. Acta Neu- rochir (Wien) 1978;45:89–101. 5 Frim DM, Goumnerova LC. Telemetric intra- ventricular pressure measurements after third ventriculostomy in a patient with noncommu- nicating hydrocephalus. Neurosurgery 1997;4: 1425–8. –1

Neuronal activity alters local blood flow in brain tumour adjacent to the activating cortex Concentration changes (au) Characteristics of blood flow in brain tu- –2 mours have been studied extensively1; these studies are important for diagnosis of malig- nancy and therapy monitoring. Our study is the first to consider how activity dependent changes of regional cerebral blood flow (rCBF) alter tumour blood flow in the brain –3 tumour adjacent to the activating cortex. 10 s 554 Letters, Correspondence, Book reviews, Correction tasks. We monitored concentration changes that a stealing of blood flow is one of the lasted for about 10–25 minutes and were fol- of oxy-Hb, deoxy-Hb, and total-Hb, using an mechanisms.4 The present report supports lowed by a hemicranial, throbbing NIRO-500 instrument (Hamamatsu Photon- this hypothesis. which was often associated with nausea, pho- ics KK, Japan). The optodes were placed at KAORU SAKATANI tophobia, and occasionally vomiting. Head- an interoptode distance of 3.5 cm on the left HUANCONG ZUO ache used to last for about 4 to 18 hours and forehead so that the centre of the two optodes YENG WANG would respond to either ergot drugs or was placed on the centre of the tumour. With Department of Neurosurgery, China-Japan Friendship sumatriptan, especially if taken at the begin- an optode distance of 4 cm, correlations of Hospital, Beijing, China ning of the episode. Occasionally these visual oxy-Hb and total-Hb measured by NIRS and WEMARA LICHTY symptoms were not followed by headache. rCBF measured by PET suggested that the Group of Detection and Analysis of Human Body The patient would not lose contact with the reliable penetration depth of near infrared Movement, Program of BME, Department of Electrical environment during or after the visual symp- light into brain tissue is about 1.3 cm3; thus Engineering, Tsinghua University, Japan toms. Her mother and two younger sisters the present NIRS measurement area was KIYOMI YABU were also having paroxysmal episodes of restricted in the tumour. The patient was Department of Rehabilitation, Takahashi common migraine. seated and had his eyes open during the Neurosurgical Hospital, Japan Her general physical and neurological NIRS measurement. Informed consent was Correspondence to: Dr Kaoru Sakatani, Depart- examination in between the episodes was obtained from the patient. ment of Neurosurgery, China-Japan Friendship unremarkable. Neurological examination To activate the left frontal lobe, we used the Hospital, Yinghua East Rd., Hepingli, Beijing during the aura symptoms disclosed that she following four tasks: (1) semantic verbal 100029, People’s Republic of China. Telephone was unable to see simultaneously all the fluency, which entails naming as many items (fax) 0086 10 64203246; email sakatani@ objects in the visual field (simultagnosia). She public.east.cn.net in a semantic category (for example, animals) did omit several words while reading a as possible; (2) confrontational naming, paragraph. However, she could comprehend which involves naming ordinary items pre- 1 Terada T, Miyamoto K, Hyotani G, et al. Local and read each and every word individually. blood flow changes in malignant brain tumors sented by the tester; (3) backward digit span, under induced hypertension. Acta Neurochir On being shown a complex picture compris- a working memory task which involves (Wien) 1992;118:108–11. ing multiple subunits she was not able to reporting of digits (2 to 8) in the reverse 2 Fox PT, Raichle ME. Focal physiological comprehend and perceive the entire picture uncoupling of cerebral blood flow and oxida- order; (4) reading, which entails reading a tive metabolism during somatosensory stimu- but was able to perceive all the components of short descriptive passage aloud. The speech lation in human subjects. Proc Natl Acad Sci the picture individually (seeing in piecemeal). responses of the patient to the tasks were USA. 1986;83:1140–4. These aforementioned features were consist- 3 Hock C, Villringer K, Müller-Spahn F, et al. normal. Decrease in parietal cerebral hemoglobin ent with simultagnosia. Besides simultagno- Figure B shows an example of changes in oxygenation during performance of a verbal sia, she had optic ataxia as evidenced by her NIRS during the naming task. After the fluency task in patients with Alzheimer’s inability to coordinate hand and eye move- beginning of the task, oxy-Hb and total-Hb disease monitored by means of near-infrared ments. Optic ataxia was tested as follows: spectroscopy (NIRS)-correlation with simulta- decreased to negative values during the task, neous rCBF-PET measurements. Brain Res each eye was tested separately and the hand and deoxy-Hb also decreased. These changes 1997;755:293–303. ipsilateral to the eye being tested was used. returned to the control level gradually after 4 Sakatani K, Xie Y, Lichty W, et al. Language- The target stimulus wasa5mmlong pin with activated cerebral blood oxygenation and the end of the task. The other tasks also hemodynamic changes of the left prefrontal a white head placed at preselected locations. caused similar changes of oxy-Hb, total-Hb, cortex in poststroke aphasic patients: a near The patient was asked to touch this pin with and deoxy-Hb. infrared spectroscopy study. Stroke 1998;29: her index finger without shifting her gaze The rCBF in the left frontal lobe is gener- 1299–304 from the fixation point. The patient had diY- 5 Hoshi Y, Onoe H, Watanabe Y, et al. Non- ally increased by all the tasks used in the synchronous behavior of neuronal activity, oxi- culty in performing this test but had no prob- present study.3–5 Indeed, our NIRS activation dative metabolism and blood supply during lems in reaching out to her own body parts or study using the cognitive tasks showed mental tasks in man. Neurosci Lett 1994;172: an auditory stimulus with her eyes closed. 129–33. increases in oxy-Hb and total-Hb in the left These features were consistent with optic frontal lobe in most normal adults—for ataxia. Moreover, gaze apraxia was evident by example, increases in oxy-Hb and total-Hb— Migraine aura masquerading as Balint’s her inability to look at an object on were found in 92.3% of young adult subjects syndrome command. However, she could do it sponta- (mean (SD) 28.8 (4.4) years) during the neously. In addition, she had impaired word fluency task (unpublished data). There- Migraine is a common neurological disorder smooth pursuit and voluntary saccades in all fore, although we could not measure the with a prevalence of 0.5% to 2% in the directions. Reflex eye movements were nor- changes in rCBF in the left frontal lobe of the general population.1 In one fourth of total mal. Visual acuity during the episode was 6/6 patient, the evidence from our previous stud- migraineurs, headache is preceded by an bilaterally. Visual fields were also normal ies strongly suggests that the tasks caused an aura.2 We describe a patient with recurrent during the episode as demonstrated by the increase in rCBF in the left frontal lobe of the episodes of migraine in whom headache was confrontation method. Ophthalmological ex- patient. preceded by a constellation of visual symp- amination, including perimetry performed The decrease in oxy-Hb and total-Hb tomatology which constituted salient compo- during a symptom free period, was normal. recorded from the brain tumour indicates a nents of Balint’s syndrome. This syndrome, There was no clinical evidence of Gerstmann decrease of local blood flow in the tumour consisting of a triad of simultagnosia, optic syndrome, prosopognosia, object agnosia, or because the NIRS measurement area was ataxia, and oculomotor apraxia, is seen with colour agnosia. Her cranial CT and magnetic restricted to the brain tumour.3 The de- bilateral lesions of occipitoparietal cortices resonance angiography were unremarkable. creases in oxy-Hb and total-Hb were found aVecting connections between visual cortical Electroencephalography was also non- only during the tasks; consequently, these regions and the frontal eye field.3 contributory. The frequency of visual aura changes were probably not due to changes in A 29 year old female teacher presented symptoms and headache decreased consider- systemic blood pressure, which can alter with an 8 year history of paroxysmal alternat- ably after the patient was started on flunar- tumour blood flow.1 Based on these assump- ing hemicranial and throbbing headache izine at a daily dosage of 10 mg at bed time. tions, we suggest that the increase of rCBF in which was often associated with nausea and The visual impulses, after being received by the left frontal lobe induced by the tasks stole photophobia. Patients fulfilled the requisite the primary visual cortex (Brodmann area the local blood flow of the brain tumour criteria for establishing the diagnosis of 17), are interpreted and integrated in visual through the cortical branches, leading to the migraine with aura as devised by the association areas 18 and 19. Brodmann area decrease of local blood flow in the tumour. International Headache Society (1988).4 She 19, in turn, is connected with the angular The present report suggests that activity used to have six to eight episodes of headache gyrus and frontal eye field by virtue of associ- dependent increase in rCBF can steal blood a month. There was no history of status ation fibres. Any lesion in the visual associ- flow from the adjacent tissues including non- migranosus during these years. On several ation areas or their connections would result activating cortex. Recent NIRS activation occasions, headache was preceded by a pecu- in impaired integration of visual impulses studies have shown that cognitive tasks cause liar constellation of visual symptomatology despite normal visual acuity. decreases in oxy-Hb and total-Hb in the left comprising distortion of visual images fol- The visual symptom complex in this case frontal lobe in some normal subjects45; these lowed by inability to perceive simultaneously possibly represents an aura of migraine. The decreases indicate a decrease in rCBF.5 objects in the visual field and touch an object pathogenesis of migraine aura has been a Although the physiological mechanisms of under direct visual guidance. However, she debatable issue.5 in this case it is suggested that the decrease in rCBF during neuronal activity could see the component parts of objects the pathophysiological process of migraine have not yet been elucidated, we hypothesise during the episode. These visual symptoms aura results in a disconnection syndrome by Letters, Correspondence, Book reviews, Correction 555 involving visual association areas and their ing, walking, and continent but with some neurological reactions, including postvacci- association pathways. Optic ataxia, gaze persistent emotional liability and mild nation , in up to 1 in 220 apraxia, and simultagnosia seem to represent a memory impairment. A follow up MRI courses, with a 3% mortality.3 Clinical forms dissociation of visual information from the examination 5 weeks after discharge showed include a reversible mononeuritis multiplex, frontal eye field and dorsal parietal regions. further improvement, apart from minor and meningoencephalitic and encephalomy- PARVAIZ A SHAH abnormalities in the basal ganglion, and gen- elitic reactions. Myelin basic protein and A NAFEE eralised increase in ventricular size, consist- related neural proteins from the nervous Division of Neurology, Department of Medicine, ent with residual cerebral atrophy. tissue of the animal on which the virus was Government Medical College and Associated SMHS Rabies is caused by an RNA virus, a mem- cultivated stimulate an autoimmune reaction Hospital, Srinagar, Kashmir, J and K 190001, India ber of the Rhabdoviridae family, it infects in the human nervous system. Correspondence to: Dr Parvaiz A Shah, Firdousa- mammals and can be transmitted to humans Tolerance has been improved by the devel- bad, Batmaloo, Srinager, Kashmir, J and K 190001, by contact, generally from an animal excret- opment of the suckling mouse brain vaccine India. Telephone 0091 194 452379. ing the virus in the saliva. Rabies manifests as (SMBV). The attenuated virus is cultured on an acute encephalomyelitis, the development immature mouse brain tissue, which contains 1 Ziegler DK. Headache: public health problem. of which is almost invariably fatal. The little myelin, thus reducing the risk of compli- Neurol Clin 1990:8:781–91. distinction between rabies and postvaccine cations. SMBV is inexpensive (US$1.5 per 2 Campbell JK. Manifestations of migraine. Neu- is diYcult and may be helped by rol Clin 1990:8:841–55. treatment course) and easily manufactured 3 Damasio AR, Tranel D. Disorders of higher antigen detection via a skin biopsy; however, 1 locally; it is the most widely used postexposure brain function. In: Rosenberg RN, ed. Compre- this technique is not available in Vietnam. hensive neurology. New York : Raven Press, Paralytic rabies could not be excluded in this vaccine in Vietnam. Rare neurological reac- 1991:639–57. tions do occur with SMBV, Complications of 4 Headache classification Committee or Inter- patient and hence steroids were not used ini- national Headache Society. Classification and tially. Steroids have been reported to increase the CNS have been reported to occur after diagnostic criteria for headache disorders, cra- mortality in experimental animals with ra- vaccination with an incidence of 1:27000 nial neuralgias and facial pain. Cephalalgia treated people, with a 22% mortality4 The 1988;3(suppl 7):1–96. bies, and it has been suggested that they may 5 Blau JN. Migraine: theories of pathogenesis. abrogate the immune response to the postex- mortality was particularly high (90%) if there Lancet 1992;339:1202–6. posure vaccine, thus precipitating uncon- was extensive CNS involvement. The third trolled rabies.2 type of vaccine available is the human diploid There are three types of postexposure vac- cell tissue culture vaccine (HDCV), which is “Can’t you use another vaccine”? cine in use world wide. The Semple type both safe and eYcacious. However, the recom- postrabies vaccination encephalitis (STV) is obtained from inactivated virus pre- mended regimen is not aVordable in most pared on adult animal nerve tissue; it is inex- developing countries. A healthy 39 year old man was bitten on the pensive and relatively easy to produce. In When we approached the Rabies Labora- ankle by his own apparently normal dog. After India 3 million people receive postexposure tory, Ministry of Agriculture and Fisheries, the incident the dog disappeared into the courses of STV (phenolised sheep brain) United Kingdom for advice in this case their forest and was not seen again. Three days later 1 antirabies vaccine each year. These produce comment was “why do you use the SMBV, the patient was seen at a provincial hospital in can’t you use another vaccine”. Worldwide Vietnam and started on an alternate day regi- about 10 million people each year receive men of suckling mouse brain postrabies expo- sure vaccination (SMBV). After the second rabies vaccine after exposure; at the Centre dose, he felt unusually lethargic although he for Tropical Diseases we treat 3000 people was still able to work. After the third dose, he with dog bites annually. The cost of an became unrousable, and was transferred to the HDCV in Vietnam, administered in its Centre for Tropical Diseases, Ho Chi Minh present regimen (1ml given for 5 days on days City, the referral hospital for infectious dis- 0, 3, 7, 14, and 28 with an optional booster on eases in southern Vietnam. On admission, he day 90) is US$ 125, making the use of this was afebrile, confused, had slurred speech, and vaccine unaVordable. his Glasgow coma score was 13. He had mild This is the first report to show the demyeli- spastic weakness of his left face, left arm, and nating CNS lesions on MRI, and their both legs. Full blood count and results from resolution after steroid therapy. It is relatively routine biochemistry and chest radiography rare for patients to survive if they develop were all normal. The CSF: blood glucose ratio severe CNS eVects after postexposure rabies was 0.47 (63/140 mg%), the protein content vaccination. Although the incidence of reac- was raised (78 mg/dl), and there was one tions to SMBV is very much lower than STV, lymphocyte/ml in the CSF. Screens for malaria this report confirms that it does still occur. toxoplasmosis, cryptococcus, and neurocyst- Both SMBV and STV are widely used icercosis were negative, as was a CSF gram throughout the developing world, and would stain. The CSF was sterile after 2 weeks of be the vaccine administered to travellers culture. Brain MRI (Access Toshiba LPT exposed to animal bites in such countries. 6.01p, 0.064 Tesla) showed areas of high signal This case stresses the need for high dose ster- throughout the white matter, and cystic-like oids in postexposure vaccine encepahlitis and change in the basal ganglion and right cerebel- the urgent need for the development and lar hemisphere (figure A). These variably sized deployment of a safe, and critically, aVord- lesions were bilateral, widely distributed, able postrabies exposure vaccine regimen. asymmetric, and showed no evidence of The economic low dose multisite intradermal haemorrhage or mass eVect. regimen using the HDCV provides an exam- As paralytic rabies could not be excluded ple of how this goal may be achieved although he was managed conservatively and the it is not yet widely accepted. Such a vaccine SMBV course was continued. On the 4th day regimen (0.1 ml HDCV given at multisite after admission he deteriorated with a injections on days 0, 7, 28, and 90) could be Glasgow coma score of 10, and was inconti- made aVordable, and oVers excellent protec- nent of urine and faeces with generalised tion without the risks of postexposure im- spastic paraparesis. Methylprednisolone (500 mune mediated encephalitis.5 mg/ day) was given for 5 days followed by a reducing course of prednisone for a presump- N V V CHAU tive diagnosis of postvaccination encephalitis. TTHIEN The SMBV was stopped. Within 72 hours of Centre for Tropical Diseases, 190 Ben Ham Tu, District starting steroids there was a dramatic im- 5, Ho Chi Minh City, Vietnam provement in his neurological state. An MRI Brain MRI in May 1997. (A) T2 weighted R SELLAR image showing multiple areas of high signal in examination performed 4 weeks later showed Department of Clinical Neurosciences, Western General the cerebral white matter. Bilateral subcortical Hospital, Edinburgh, UK a marked decrease in both size and number of and periventricular lesions are seen. (B) Brain brain lesions and no new lesions (figure B). MRI in July 1997. T2 weighted image shows R KNEEN After 6 weeks he was discharged talking, eat- resolution of the white matter lesions. J J FARRAR 556 Letters, Correspondence, Book reviews, Correction

Wellcome Trust Clinical Research Unit, Centre for normal results. Tests for HIV antibody, presentation is a necrotising vasculitis, a well Tropical Diseases, 190 Ben Ham Tu, District 5, Ho serum angiotensin converting enzyme, white described complication of oral amphetamine Chi Minh City, Vietnam cell enzymes, and serum and urinary porphy- misuse.5 The clinical features, MRI appear- R KNEEN rins were negative. Erythrocyte sedimenta- ance, brain biopsy, absence of haemorrhage, J J FARRAR tion rate on admission was 58 mm/h. and lack of response to steroids make this Centre for Tropical Medicine, NuYeld Department of Examination of the CSF showed normal unlikely. Clinical Medicine, John RadcliVe Hospital, University opening pressure, protein 0.27 g/l, glucose The likely precipitant of this man’s illness of Oxford, UK 4.3 mmol/l (blood glucose 6.1 mmol/l), and seems to be his use of khat. A drug screen on Correspondence to: DrJJFarrar, Wellcome Trust no cells. His initial EEG was abnormal with admission was negative, and his family denied Clinical Research Unit, Centre for Tropical Dis- diVuse slow waves indicative of widespread misuse of other drugs. It remains possible eases, 190 Ben Ham Tu, District 5, Ho Chi Minh cerebral dysfunction. that the sample of khat chewed by this man City, Vietnam A chest radiograph and ultrasound exam- was contaminated. We are unaware of any ination of the abdomen were normal. Cranial previous reports of khat misuse with severe 1 Warrell MJ, Warrell DA. Rhabdoviruses: rabies MRI, although contaminated by movement neurological deterioration; previous cases and rabies related viruses. In: Weatherall DJ, artefact, showed diVuse abnormality in the may not have been investigated or reported. Ledingham JGG, Warrell DA, eds. Oxford text- deep cerebral white matter of both cerebral In reporting this case our intention is to alert book of medicine. 3rd ed. Oxford: Oxford University Press, 1996:394–405. hemispheres. Fourteen days after admission he others to a possible complication of the mis- 2 Fishbein DB, Bernard KW. Rabies virus. In: was witnessed to have a single brief adversive use of this drug. Evidence of other cases Mandel GL, Douglas RG, Bennett JE, eds. seizure with eye and head deviation to the would provide a powerful argument for the Principle and practice of infectious diseases. 4th ed. New York: Churchill Livingstone, 1995:1527– right. restriction of import and sale of khat. 43. The patient was admitted to a rehabilita- P K MORRISH 3 Swaddiwudhipong W,Prayoonwiwat N, Kuna- tion unit. His mini mental state examination N NICOLAOU sol P, et al. A high incidence of neurological score and Barthel scores were zero. Feeding complications following Semple anti-rabies P BRAKKENBERG vaccine. Southeast Asian J Trop Med Public by percutaneous gastrostomy was started. A P E M SMITH Health 1987;18:526–3. trial of intravenous methylprednisolone (1 g Department of Neurology, University Hospital of 4 Toro G; Vergara I; Roman G. Neuroparalytic on 3 consecutive days) gave no benefit. Wales, Heath Park, CardiV CF4 4XN, UK accidents of antirabies vaccination with suck- Repeated EEGs (on four occasions) showed ling mouse brain vaccine. Clinical and patho- Correspondence to: Dr PK Morrish, Department logic study of 21 cases. Arch Neurol 1977;34: diVuse slow waves only. A second MRI of Neurology, University Hospital of Wales, Heath 694–700. (figure) 3 months after onset of symptom Park, CardiV CF4 4XN, UK. Telephone 0044 1222 5 Warrell MJ, Nicholson KG, Warrell DA, et al. showed the presence of a continuing diVuse 747747; fax 004 1222 744166; email: Economical multiple-site intradermal immuni- [email protected] sation with human diploid cell strain vaccine is extensive abnormal signal in the deep white eVective for post-exposure rabies prophylaxis. matter of both cerebral hemispheres with Lancet 1985;i:1059–62. marked cortical atrophy. Brain biopsy (via 1 Pantelis C, Hindler CG, Taylor JC. Use and right frontal craniotomy) was performed 3 abuseofkhat(Catha edulis): a review of the months after the onset of his illness. There distribution, pharmacology, side eVects and a Leukoencephalopathy associated with was no evidence of acute inflammation, description of psychosis attributed to khat khat misuse chewing. Psychol Med 1989;19:657–68. vasculitis, or infarction. 2 Khattab NY, Galal A. Undetected neuropsycho- While undergoing rehabilitation there has logical sequelae of khat chewing in standard The leaves of the tree Catha edulis, or khat been slow improvement in his cognitive and aviation medical examination. Aviat Space (also qat and kat) are chewed by a large pro- locomotor function. After 1 year he is able to Environ Med 1995;66:739–44. 3 Celius EG, Andersson S. Leucoencephalopathy portion of the adult population of the Yemen, open and close his eyes, occasionally verbal- and throughout Saharan and sub-Saharan after inhalation of heroin: a case report. J Neu- ise, localise pain, and obey simple commands. rol Neurosurg Psychiatry 1996;60:694. Africa. The leaves are also chewed by His plantars are flexor but he has persistent 4 Walters EC, van Wijngaarden GK, Stam FC, et members of the Yemeni and Somali commu- grasp and palmomental reflexes. His nutri- al. Leucoencephalopathy after inhaling nity in the United Kingdom.1 The psychoac- “heroin” pyrolysate. Lancet 1982;ii:1233–7. tion is maintained by gastrostomy and he has 5 Salanova V, Taubner R. Intracerebral haemor- tive constituents of khat are cathin (d- an indwelling catheter. rhage and vasculitis secondary to amphetamine norisoephedrine), cathidine, and cathinone The clinical presentation, EEG, and MRI use. Postgrad Med J 1984;60:429–30. (an alkaloid with a structure resembling findings suggest a rapidly progressive leu- ephedrine and amphetamine) and users koencephalopathy. There are no previous report a mild euphoria similar to that of Necrotising vasculitis with conduction 1 reports of leukoencephalopathy in association amphetamine. Khat is acknowledged as a with khat or amphetamine misuse; it has, block in mononeuropathy multiplex precipitant of psychosis and has also been with cold agglutinins 2 however, been reported in association with reported to cause cognitive impairment. We other recreational drugs taken by mouth or report a case in which khat chewing has been inhalation.34 An alternative for this man’s Cold agglutinins are cold reactive autoanti- associated with a severe and disabling neuro- bodies that have haemolytic eVects on red logical illness. blood cells mediated via complement fixa- A 56 year old Somali living in the United tion. Neuropathy associated with cold agglu- Kingdom for the past 18 years was admitted to tinins has been described,1–5 however, details a psychiatric hospital witha5weekhistory of of its pathomechanism are unclear. Here, we progressive confusion and agitation. His family report the clinical, electrophysiological, and reported that he had been chewing khat, in pathological findings of a mononeuropathy their opinion to excess, every day during that multiplex in a patient with cold agglutinins, time but had stopped 2 days before admission. who responded very well to plasmapheresis. There was one previous admission to hospital A 72 year old man was admitted with a 1 9 months previously with khat induced psy- month history of progressing dysaesthesia and chosis, from which he recovered without com- weakness of the limbs. He had no anaemia, plications within 24 hours. On this occasion, jaundice, hepatosplenomegaly, or lymphaden- shortly after admission, his conscious level opathy. Cranial nerves and the cerebellum deteriorated abruptly and he was referred for were not involved. There was severe weakness neurological opinion. He was apyrexial and and atrophy of bilateral thenar, interossei, and general medical examination was normal. He plantar muscles with severe dysaesthesia of opened his eyes spontaneously but there was both palms and plantaris. Pin prick and light no verbal response and he did not obey touch were reduced as well as position and commands. He withdrew all four limbs to vibratory sensation in both hands and feet. pain. Upper and lower limbs were held in flex- Deep tendon reflexes were hypoactive. Babin- ion with markedly increased tone. Reflexes ski’s sign was negative. were brisk but equal. The right plantar was Laboratory investigation showed a raised extensor. There were bilateral palmomental erythrocyte sedimentation rate: 52 mm/hour and grasp reflexes. Cranial MRI 3 months after onset of symptoms (normal <10) and serum C reactive protein: Full blood count, urea and electrolytes, showing diVuse signal abnormality in the deep 1.8 mg/dl (normal; < 0.5). Blood cell counts glucose, liver function tests, thyroid function white matter of both cerebral hemispheres. There were within normal limits. The following test, viral serology, and malaria screen all gave is also marked cortical atrophy. were normal or negative; IgG, IgA, IgE, IgM, Letters, Correspondence, Book reviews, Correction 557

M-protein, direct and indirect Coombs tests, aesthesia and muscle strength improved re- may be as follows. Firstly, conduction block cryoglobulin, antibodies to mycoplasma, my- markably.The titre of cold agglutinins was may occur as a consequence of nerve ischae- elin associated glycoprotein, gangliosides reduced to 1:64. The motor nerve conduction mia due to small vessel occlusion. There have (GM1, GD1b, asialo-GM1, GT1b, GQ1b, velocity (MCV) of the right median nerve like- been reports of conduction block occurring in Gal-C), P-ANCA, and C-ANCA. The CSF wise improved (pretreatment; 40.0 m/s, post- vasculitic neuropathy which support this possi- was normal. Titre of cold agglutinins was treatment; 57.0 m/s). Double filtration plas- bility. Secondly, humoral factors including detectable at 1:1024 at 4°C (normal; mapheresis was followed by oral azathioprine cold agglutinins may induce immune medi- <1:256). The patient’s serum agglutinated (50 mg/day) with tapering of steroid. He was ated demyelination in the peripheral nervous adult group OI-red blood cells, but not discharged on prednisolone (20 mg/day). In system. Taken together, neuropathy with cold Oi-red blood cells or human cord red blood the subsequent 4 years, he has had mild exac- agglutinins may involve immunologically me- cells, signifying cold agglutinins with I erbation of dysaesthesia that responded to diated demyelination, microcirculation occlu- specificity. Immunoelectrophoresis of the intermittent steroid therapy. sion, and vasa nervorum vasculitis. The diver- eluate confirmed IgM composition. Characteristic features of the present case sity of pathomechanisms may come from the The initial nerve conduction study showed are as follows: (1) subacute onset of monone- diVerence target antigens recognised by cold severe diminution or absence of compound uropathy multiplex; (2) necrotising vasculitis agglutinins. Plasmapheresis proved eVective in muscle action potentials (CMAPs) with with marked loss of myelinated fibres; (3) all cases. These findings strongly suggest that mildly diminished conduction velocities. F probable conduction block in the median humoral factors including cold agglutinins wave latencies were mildly prolonged. There nerve; (4) increased concentrations of serum may play an important part in the induction of were no evoked sensory nerve action poten- titres of cold agglutinin; and (5) marked neuropathy with cold agglutinins. We re- tials (SNAPs) in median, ulnar, and sural response to plasmapheresis. Extensive inves- commend plasmapheresis as first choice treat- nerves bilaterally. Electromyographic studies tigation for other causes of neuropathy was ment for neuropathy associated with cold of the aVected muscles showed moderate negative except for an increased serum agglutinins. neurogenic changes, but there were no fibril- concentration of cold agglutinins, which We thank Dr Gerard Salazar for critical reading of lation potentials except in the left anterior strongly suggests that cold agglutinins may the manuscript, Ms M Teshima and N Hirata for tibialis muscle. Sural nerve biopsy was play an important part in the induction of their technical assistance, Dr S Kusunoki (Depart- performed. Epineurial vessels were sur- neuropathy in this case. ment of Neurology, Institute for Brain research, rounded by mononuclear cell infiltrates Six patients with neuropathy associated with University of Tokyo) for analyses of antibodies to 1–5 gangliosides, and Mr H Moug (Division of Blood (figure A). Some vessels had focal necrosis of cold agglutinins have been reported includ- Transfusion Medicine, University of Kagoshima) their wall. The small vessels in the endoneu- ing our patient. Cold agglutinins are cold reac- for characterization of cold agglutinin. rium and epineurium showed slugging of red tive autoantibodies that react with the anti- R OTSUKA blood cells. The densities of large and small genic determinant termed I/i or Pr present on F UMEHARA myelinated fibres were markedly decreased glycoproteins and glycolipids in erythrocyte K ARIMURA (diameter<5 µm: 1504/mm2, diameter >5 membranes. Arai et al1 reported a case of Y MARUYAMA µm:708/mm2, total: 2212/mm2)(figure B). polyneuropathy and IgMê M proteinemia Y ARIMURA Teased fibre analysis showed that 90% of the with anti-Pr2 CA activity. IgM M protein cross M OSAME fibres were undergoing axonal degeneration. reacted with sialosyl paragloboside, GT1b, The Third Department of Internal Medicine, Oral prednisolone (30–50 mg/day) for 4 GD1a, GD1b, GM3, and GD3 present in Kagoshima University School of Medicine, Sakuragaoka 8–35–1 Kagoshima, Japan weeks reduced the erythrocyte sedimentation myelin and in endothelial cells of the periph- rate and C reactive protein, but not the serum eral nervous system. It has been speculated Correspondence to: Dr R Otsuka, The Third Department of Internal Medicine, Kagoshima titre of cold agglutinins; neither was there any that anti-Pr2 IgM protein induced immune University School of Medicine, Sakuragaoka improvement of symptoms. He received mas- mediated damage to vascular endothelium and 8–35–1 Kagoshima, Japan. Telephone 0081 99 275 sive dose intravenous corticosteroid therapy. peripheral nervous system myelin. A similar 5332; fax 0081 99 265 7164; email This moderately improved the muscle strength pathomechanism has been postulated in the [email protected] and sensory disturbance. Follow up nerve other cases.2–3 However, necrotising vasculitis conduction studies (71 days after the initial has never been reported in neuropathy with 1 Arai M, Yoshino H, Kusano Y, et al. Ataxic study) suggested conduction block of the right cold agglutinins. This is the first demonstra- polyneuropathy and anti-Pr2 IgMê M pro- teinemia. J Neurol 1992;239:147–51. median nerve on the forearm (CMAP, dura- tion of vasculitic neuropathy with cold aggluti- 2 Willison HJ, Paterson G, Veitch J, et al. Periph- tion at the wrist: 2.76 mV, 8.4 ms; CMAP, nins. Although the mechanism for neuropathy eral neuropathy assaciated with monoclonal duration at the elbow: 1.87 mV, 8.8 ms), with cold agglutinins is unknown, mechanisms IgM anti-Pr2 cold agglutinins. J Neurol Neuro- whereas CMAP could not be elicited in the similar to those in cryoglobulinaemic neu- surg Psychiatry 1993;56:1178–83. 4 3 Herron B, Willison HJ, Veitch J, et al. Mono- initial study. We adapted the following criteria ropathy have been postulated. The hypotheses clonal IgM cold agglutinins with anti-Pr1d to define conduction block: <15% change in are (1) immunologically mediated demyelina- specificity in a patient with peripheral neu- duration and >20% fall in negative peak tion; (2) ischaemic injury secondary to slug- ropathy. Vox Sang 1994;67:58–63. 4 Thomas TD, Donofrio PD, Angero J. Peripheral amplitude between proximal and distal sites by ging or agglutination of red blood cells in the neuropathy in cold agglutinin disease. Muscle percutaneous supramaximal stimulation of vasa nervorum; and (3) an associated vasculi- Nerve 1991;14:331–4. motor nerves. As the conduction block might tis. In the present case, we have confirmed the 5 Valbonesi M, Guzzini F, Zerbi D, et al. Success- delay smooth recovery of symptoms, Double necrotising vasculitis and probable conduction ful plasma exchange for a patient with chronic demyelinating polyneuropathy and cold agglu- filtration plasmapheresis was performed four block. Pathophysiological explanations for tinin disease due toanti-Pra. J Clin Apheresis times. After the second plasmapheresis, dys- association of vasculitis and conduction block 1986;3:109–10.

(A) Sural nerve (toluidine blue staining) showing epineurial vessel surrounded by mononuclear cell infiltrates. Note fibrin deposition (arrow) and necrosis in media. (bar=20 µm). (B) Most of myelinated fibres are undergoing axonal degeneration. Many macrophages containing myelin debris infiltrate the endoneurium. (bar=30 µm). 558 Letters, Correspondence, Book reviews, Correction

mon factor in most studies in this field and is 1 Kaufer DI, Cummings JL, Christine D. EVect of worthy of some explanation in its own right. tacrine on behavioral symptoms in Alzheimer’s disease: an open label study. J Geriatr Psychiatr CORRESPONDENCE Although it seems that these studies compare Neurol 1996;9:1–6. drug treatment with that of a placebo (one 2 Bodick N, OVen W, Levey AI, et al.EVects of treatment against no treatment), the reality is xanomeline, a selective muscarinic agonist, on that it is a comparison of patients receiving cognitive function and behavioral symptoms in Alzheimer’s disease. Arch Neurol 1997;54:465–73. two treatments against other patients who are 3 Cummings JL, Back C. The cholinergic hypo- The cholinergic hypothesis of receiving one form of treatment. The addi- thesis of neuropsychiatric symptoms in Alzheimer’s disease: a review of tional treatment regime is, of course, the care Alzheimer’s disease. Am J Geriatr Psychiatry and attention that they receive by being part 1998;6:S64–78. progress 4 Kaufer DI, Catt K, Pollock BG, et al. Donepezil of the clinical study, which often seems to in Alzheimer’s disease: relative cognitive and have an impact, not just on the patient but neuropsychiatric responses and impact on care- I read with interest the review of Francis et al also on their main carer or carers. giver distress. Neurology 1998;19(suppl 4): regarding the progress of the cholinergic As far as behavioural disturbances are S182. 1 5 Morris JC, Cyrus PA, Orazem J, et al. Metri- hypothesis of Alzheimer’s disease. They concerned, however, our review was making fonate benefits cognitive, behavioral and global mentioned that donepezil produced improve- the point that evidence is emerging from clini- function in patients with Alzheimer’s disease. ment or no deterioration in more than 80% of cal trials to suggest that cholinomimetic drugs Neurology 1998;50:1222–30. patients, and that such responses should be 6 Cummings JL, Kaufer D. Neuropsychiatric as a whole may have a beneficial eVect on some aspects of Alzheimer’s disease: the cholinergic viewed positively considering the progressive, non-cognitive behavioural symptoms. This has hypothesis revisited. Neurology 1996;47:867–83. degenerative nature of the disease. Various now been reported for at least two cholinest- 7 Hutchinson M, Fazzini E. Cholinesterase inhi- donepezil manufacturer’s medical repre- erase inhibitors, and two muscarinic bition in Parkinson’s disease. J Neurol Neuro- surg Psychiatry 1986;61:324–5. sentatives presenting data from a clinical agonists.1–5 In particular, a clear link is emerg- 2 8 Perry EK, Marshall E, Kerwin J, et al. Evidence study also commonly use this statement. ing between psychotic symptoms and cholin- of a monoaminergic-cholinergic imbalance However, this only partially reveals the truth. ergic dysfunction. Thus, Bodick et al2 have related to visual hallucinations in Lewy body . 1990; :1454–6. In fact, the same study produced improve- shown that the M /M agonist xanomeline J Neurochem 55 1 4 9 Bymaster FP, Shannon HE, Rasmussen K, et al. ment or no deterioration in 59% patients on causes a dose dependent reduction in halluci- Unexpected antipsychotic-like activity with the placebo. I think that the beneficial eVect of nations, agitation, and delusions in a 6 month muscarinic receptor ligand (5R,6R)6-(3- donepezil in particular clinical trials should randomised double blind placebo controlled, propylthio-1,2,5-thiadiazol-4-yl)-1- always be critically reviewed in comparison azabicyclo[3.2.1]octane. Brain Res 1998;795: parallel group trial. In addition, Cummings 179–90. with placebo. In addition, as both 24 week and Kaufer6 have shown that the cholinest- 10 Hong CH, Woo JI, Suh YH, et al.EVect of placebo controlled donepezil trials performed erase inhibitor tacrine is more eVective in ketamine on the acetylcholine concentration of so far excluded patients with behavioural dis- various regions of rat brain. Seoul Journal of reducing psychotic features than cognitive dis- Medicine 1987;28:347–51. turbances, my impression is that the positive turbances; tacrine also reduces or abolishes eVect of donepezil on the symptoms of hallucinations in Parkinson’s disease.7 Another behavioural disturbances still remains con- cholinesterase inhibitor, metrifonate, was also troversial. In fact there are reports that shown to reduce the number of hallucinations donepezil might induce behavioural distur- in a 26 week randomised, double blind, 34 BOOK REVIEWS bances in patients with Alzheimer’s disease. placebo controlled safety and eYcacy study in Therefore I would be extremely cautious patients with Alzheimer’s disease. Further about prescribing donepezil to patients with support for a link between acetylcholine and Alzheimer’ s disease accompanied by behav- psychosis derives from postmortem data show- Clinical Management of Diabetic ioural disturbances. ing that the activity of choline acetyltransferase Edited by ARISTIDIS VEVES. (Pp Finally, donepezil was never investigated in a in the temporal cortex of patients with Lewy Neuropathy. 30 week randomised double blind study as was body dementia was lower in those patients 348, US$125). Published by The Humana mentioned in the review. The authors are with hallucinations than in patients without Press, New Jersey, 1998. ISBN probably referring to the randomised 24 week this feature.8 Finally, in animals the partial 0-896-03528-X. double blind placebo controlled trial with an M2/M4 agonist (5R,6R)6-(3-propylthio-1,2,5- additional 6 week single blinded placebo thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane The neuropathies of diabetes are common (as phase. produced a preclinical profile suggestive of the chapters in this book repeatedly remind antipsychotic eYcacy9 and that the psychomi- us) and can be very disagreeable. Symptom- T BABIC less neuropathy underlies foot ulceration and Department of Neurology, Medical School University metic NMDA receptor antagonist ketamine (when administered at subanaesthetic doses) sepsis as the commonest clinical consequence of Zagreb, Kisˇaticeva 12, 10000 Zagreb, Croatia. of diabetic neuropathy but other extremely Telephone 00385 1 217280, fax 00385 1 217280, reduced brain concentrations of acetylcho- 10 unpleasant disorders range from exception- email [email protected] line. Thus, on the basis of both clinical and preclinical data, a clear rationale is emerging ally severe pain to the whole range of for prescribing cholinomimetic agents for problems resulting from autonomic failure. This book comprehensively covers every 1 Francis PT, Palmer AM, Snape M, et al. The treating the non-cognitive behavioural symp- cholinergic hypothesis of Alzheimer’s disease: a toms associated with dementia, particularly aspect of the subject, systematically (and at review of progress. J Neurol Neurosurg Psychia- psychosis. times exhaustively) from its epidemiology try 1999;66:137–47. and pathogenesis (exhaustingly) to struc- 2 Rogers SL, Farlow MR, Doody RS, et al.A Professor Babic is also correct in identify- 24-week, double-blind, placebo-controlled trial ing two of the studies referred to as the 30 tural, functional, and clinical problems and of donepezil in patients with Alzheimer’s week randomised multicentre placebo con- their treatment. Most of the authors are well disease. Donepezil Study Group. Neurology trolled parallel group studies, which included known in the field and their accounts are up 1998;50:136–45. to date and authoritiative. 3 Wengel SP, Roccaforte WH, Burke WJ, et al. a 24 week double blinded treatment phase. Behavioural complication associated with Unfortunately, struggle as they might, all donepezil. Am J Psychiatry 1998;155:1632–3. authorities have diYculty in defining what 4 Bouman WP, Pinner G. Violent behaviour- they mean by diabetic neuropathy and, in this associated with donepezil. Am J Psychiatry We are grateful to your correspondent for providing regard, understanding of this complication 1998;155:1626–7. us with the opportunity to clarify these points. both in clinical and pathological terms, as well as with regard to treatment, lags far PAUL T FRANCIS Neuroscience Research Centre, GKT School of behind that of the other classic diabetic com- The authors reply: Biomedical Science, King’s College London, London plications, nephropathy and retinopathy. We thank Professor Babic for the letter, which SE1 9RT,UK Even its classification presents problems and raises several interesting points. We agree that attempts to do so are found in four diVerent it may be more helpful to put the results ALAN M PALMER chapters, describing four classifications. Rep- attributed to treatment with donepezil in the MICHAEL SNAPE etition is an unfortunate feature of this book context of the placebo response. In general, Cerebrus Pharmaceuticals Ltd, Winnersh, Wokingham, and—quite apart from the confusion over looking at this as a class eVect in relation to RG41 5UA, UK classification—aspects of pathogenesis, struc- several compounds, the picture emerging is tural changes, epidemiology, diagrams, and that about twice as many people obtain a GORDON K WILCOCK some reference to treatment (for example, response to active treatment as to that with Department of Care of the Elderly, Frenchay Hospital, that of pain) appear repeatedly in diVerent placebo. The high placebo response is a com- Bristol, BS16 2EW,UK chapters in greater or lesser detail. Letters, Correspondence, Book reviews, Correction 559

This is certainly a book for the specialist radiosurgery, and to image guidance in Readers may be interested in: and not at all (as the preface suggests) for the epilepsy and functional surgery. The final family practitioner. There are good reviews of section is entitled Frontiers in Neurosurgical nerve structure, causation, and treatment of Navigation and considers, among other top- States of Mind. Edited by ROBERTA CONLAN. painful neuropathies and focal neuropathies. ics, intraoperative MRI, telepresence in neu- (Pp214, £19.99). Published by John Wiley The comprehensive survey of the Diabetes rosurgery, and robotics. And Sons, Chichester, 1999. ISBN Control and Complications Trial (DCCT) The incorporation of new technology is 0-471-29963-4. shows in detail the only treatment which is likely to alter surgical practice radically over truly eVective (diabetic control); and the the coming decade and equipment that lengthy description of aldose reductase in- seemed at the cutting edge of technology only First Episode Psychosis. By K AITCHISON, hibitor trials establishes that, even after more a few years ago, such as the mechanical arm, KM MEEHAN, and R MURRAY. (Pp 152, £19.95). than two decades of investigation, further has already passed into near obsolescence at a Published by Martin Dunitz, London, 1999. trials are still needed. bewildering rate. This volume provides an ISBN 1-85317-435-1. Clinical evaluation of somatic and auto- excellent account of the developments which nomic neuropathies are useful and also, to have occurred in neuronavigation, and a some extent, comprehensive but lack thought provoking insight into the wider Endoscopy in Neuro-otology. Edited By J specificity—that is, normal values for simple applications of equipment of which many of MAGNAN and M SANNA. (Pp 101, DM198). tests are di cult to find. The huge subject of Y us use only a fraction of the potential capabil- Published by Georg Thieme Verlag, the diabetic foot is covered in these chapters ity. The title of the book should perhaps have Stuttgart, 1999. ISBN 313-113061-X. and “the impact of micro and macrovascular included the word cranial, as there is almost disease” is compressed into the last nine no discussion of the impact that this technol- pages of the book. ogy has had in surgery of the spine. This aside The bibliography is important and often it is an excellent book although, like the tech- Advances in Biological Psychiatry Vol 19: very up to date with references ranging from nology it chronicles, one which is likely to New Models For Depression. Edited by D 33 to 283 per chapter. date quite rapidly. EBERT and K P EBMEIER. (Pp 204, US$170.50). If this book is at times confusing, this reflects ROBERT MACFARLANE Published by Karger, Basel, 1998. ISBN the confusion regarding the nature and treat- 3-8055-6698-0. ment of the diabetic neuropathies as much as the overlap and repetition found in its different chapters. It is a book of reference for the Key Topics in Neurology.ByPEM SMITH. Screening for Brain Dysfunction in (Pp 318, £22.95). Published by BIOS specialist who will be well served by the com- Psychiatric Patients. By COOPER B HOLMES. prehensiveness of some of its reviews and their Scientific Publishers Ltd, Oxford, 1998. (Pp 136, US$36.95). Published by Charles C assembly of the appropriate literature. ISBN 1-85996-261-0. Thomas, Illinois, 1998. ISBN 0-398- PETER WATKINS 06921-2. The title and back cover of the latest addition to Neurology Lite texts contains the usual By proclamations. “Concise, key topics, revision Advanced Neurosurgical Navigation. Management of Depression. By GIN S EBEN ALEXANDER III and ROBERT J MACIUNAS. aid, essential, review”... the well trailed MALHI and PAUL K BRIDGES. (Pp 136, £19.95). soundbites demanded by the consumer in the (Pp 605, DM398.00). Published by Thieme, Published by Martin, Dunitz Publishers, New York, 1999. ISBN 3-13-115391 1. increasingly competitive market of “read less - learn more” books. This book, however, is London 1998. ISBN 1-85317-547-1. The quest for a means of accurate localisation unusual and distinct. Unlike many rivals it is not an A5 facsimile of a superior parent A3 of structures during neurosurgery has taxed Clinical Research in Psychiatry. A the minds of clinicians from early in the reference tome. Brevity, so essential to the Practical Guide. Edited by STEPHEN history of the specialty, starting with Zernov’s success of an overview work, has sacrificed encephalometer more than a century ago. neither clarity nor clinical relevance. The CURRAN AND CHRISTOPHER J WILLIAMS. (Pp Just as the solution to the mariners’ problem strength of Key Topics in Neurology owes much 185, £17.99). Published by Butterworth of determining longitude from which it partly to the author’s ability to negotiate skilfully the Heinemann, Oxford 1999. ISBN 07506 takes its name, neuronavigation ("the sur- compromises necessary for a successful 4073 1. geon’s sextant”) has relied on the advent of distillation of a large and complex field. He new technologies to provide solutions to an has not shied from wholesale culling of age old puzzle. neurological ballast. The allied ability to dis- Advances In Neuronavigation begins by trac- tinguish and highlight the salient and relevant ing the history of stereotaxis from a Cartesian from the obscure and historical allows this coordinate system devised by Clarke and small book to be surprisingly thorough in its CORRECTION Horsley at the beginning of this century, coverage and topicality. There is suYcient up through ventriculography, stereotactic brain to date information on most areas of neurol- atlases, and CT/MR frame based stereotaxis. ogy such that this book would be useful for The final part of the first section discusses the specialist registrars albeit without the detail roots of image guided frameless stereotaxis or embellishment they seek. In terms of the through the integration of high speed graph- aims of this book such observations must be K Sudo, N Fujiki, S Tsuji, M Ajiki, T ics computers, informatics, biotechnology, regarded as complimentary. Higashi, M Niino, S Kikuchi, F Moriwaka, K and robotics. My limited criticisms relate to details of Tashiro. The remainder of the text is divided into layout and presentation. I found the exclusive Focal (segmental) dyshidrosis in syringomy- four sections. The first concerns the creation alphabetical arrangement of chapters mildly elia. J Neurol Neurosurg Psychiatry of maps from CT, MRI, MRA, PET, and disorientating in that, for example, History 1999;67:106-8. During the editorial process various types of functional imaging. The fol- taking in Neurology is to be found at p 131. the footnote to table 1(p 107) was wrongly lowing section discusses clinical applications Similarly, the absence of diagrams and tables transcribed.The last line—¶p value for each of stereotaxis, beginning with diVerent au- is an unexpected omission as I would imagine pair of items: hyperhydrosis v hyperhydrosis thors’ experiences of their own favoured that this would have complemented the over- 0.0007; hypohydrosis v normohydrosis frames, the biopsy of diYcult lesions such as all style of the book. These are minor gripes 0.7282; normohydrosis v hypohydrosis those in the brainstem or posterior fossa, and of what in print largely matches the sleeve 0.0012 should read—¶p value for each pair finally experience with diVerent image guid- hype and with a price tag of just £27-50 the of items: hyperhydrosis v hypohydrosis ance systems and their integration with the book will be welcomed by undergraduates 0.0007; hyperhydrosis v normohydrosis operating microscope and endoscope. There through to specialist registrars. 0.7282; normohydrosis v hypohydrosis then follows a series of chapters devoted to SIDDHARTHAN CHANDRAN 0.0012.