J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.163 on 1 August 1999. Downloaded from J Neurol Neurosurg Psychiatry 1999;67:163–168 163 Basal forebrain amnesia: does the nucleus accumbens contribute to human memory?

Georg Goldenberg, Uwe Schuri, Olaf Grömminger, Ursula Arnold

Abstract and anterior portions of the thalamus can Objective—To analyse amnesia caused by cause amnesia.2–7 The evidence for a selective basal forebrain lesions. role of the basal forebrain in human memory is Methods—A single case study of a patient weaker and more indirect. It has originally with amnesia after bleeding into the ante- been derived from degeneration of cholinergic rior portion of the left basal ganglia. cells within the basal forebrain in Alzheimer’s Neuropsychological examination included disease.89 As amnesia is a core symptom of tests of attention, executive function, Alzheimer’s disease it has been concluded that working memory, recall, and recognition basal forebrain lesions can cause amnesia. This of verbal and non-verbal material, and conclusion is not compelling as neuronal recall from remote semantic and autobio- degeneration in Alzheimer’s disease aVects graphical memory. The patient’s MRI and medial temporal structures as well.10 11 More those of other published cases of basal direct evidence for basal forebrain amnesia is forebrain amnesia were reviewed to provided by patients with amnesia after cir- specify which structures within the basal cumscribed damage to only the basal forebrain are crucial for amnesia. forebrain.12–22 In most of them, the lesion was Results—Attention and executive function caused by haemorrhage from anterior commu- were largely intact. There was antero- nicating artery aneurysms and subsequent inf- grade amnesia for verbal material which arction of perforating arterial branches or aVected free recall and recognition. With Heubner’s recurrent artery.12–14 16 17 19–22 How- both modes of testing the patient pro- ever, subarachnoidal or intraventricular haem- duced many false positive responses and orrhage may cause hydrocephalus and di use intrusions when lists of unrelated words V had been memorised. However, he con- brain damage. This raises the possibility that at fabulated neither on story recall nor in least some of the symptoms of these patients are due to diVuse brain damage rather than to day to day memory, nor in recall from 23 remote memory. The lesion aVected the basal forebrain lesion. mainly the nucleus accumbens, but en- The anatomicoclinical relation of basal fore- croached on the inferior limb of the brain amnesia is further complicated by the capsula interna and the most ventral por- proximity of the basal forebrain to the frontal tion of the nucleus caudatus and globus lobe. Lesions from anterior artery aneurysms pallidus, and there was evidence of some often aVect the orbital and medial frontal http://jnnp.bmj.com/ atrophy of the head of the caudate nu- lobe.12 17 24 25 Disinhibition or unconcern re- cleus. The lesion spared the nucleus basa- lated to frontal lobe pathology may distort or lis Meynert, the diagnonal band, and the conceal the amnesic syndrome.16 Particularly, septum, which are the sites of cholinergic confabulations which are a frequent feature of cell concentrations. basal forebrain amnesia have been related to Conclusions—It seems unlikely that false accompanying frontal lobe pathology rather positive responses were caused by insuY- than to the basal forebrain lesion itself.26 cient strategic control of memory re- on September 28, 2021 by guest. Protected copyright. Neuropsychological The uncertainty of the anatomicoclinical Department, trieval. This speaks against a major role of relation increases when localisation within the Bogenhausen Hospital, the capsular lesion which might discon- basal forebrain is considered. Inspired by the Munich, Germany nect the prefrontal cortex from the thala- parallel with Alzheimer’s disease, some authors G Goldenberg mus. It is proposed that the lesion of the have considered damage to cholinergic cells in U Schuri nucleus accumbens caused amnesia. O Grömminger the septum, the diagonal band, or the nucleus (J Neurol Neurosurg Psychiatry 1999;67:163–168) U Arnold basalis of Meynert as being the cause of 12 18 Keywords: amnesia; basal forebrain; nucleus accumbens amnesia. An alternative account holds that Correspondence to: lesions of fibre tracts rather than cells are cru- Dr G Goldenberg, 15 20 Neuropsychologische cial for amnesia. The basal forebrain is tra- Abteilung, Krankenhaus Research in human amnesia has identified versed by the inferior and anterior thalamic München Bogenhausen, peduncles which connect the dorsomedial Englschalkingerstrasse 77, D three core regions where localised brain 81925 München, Germany. damage can cause a lasting amnesic syndrome: nucleus of the thalamus with the amygdalae Telephone 0049 89 9270 the medial temporal lobe, the thalamus, and and with the prefrontal cortex. Amnesia may be 2106; fax 0049 89 9270 1 caused by interruption of an amygdala- 2089; email the basal forebrain. However, the weight of the [email protected] evidence for a selective correlation between thalamic-prefrontal loop rather than by basal circumscribed lesions and amnesia is diVerent forebrain damage itself.11527 Received 20 October 1998 for these three locations. There are many case In this paper we describe a patient with and in revised form 12 January 1999 reports showing that circumscribed lesions of amnesia from a circumscribed basal forebrain Accepted 19 January 1999 the medial temporal lobes and of the medial lesion which did not extend into the frontal J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.163 on 1 August 1999. Downloaded from 164 Goldenberg, Schuri, Grömminger, et al

A which had been talked about only a few minutes ago. In addition he noted an impover- ishment of his autobiographical memories and a loss of professional knowledge. He could not remember geographical facts, names of other companies, mathematical formulae, or phone numbers which he had known by heart before. He said that he had lost his previous knowledge of foreign languages. He had to translate labo- riously even English which had been the every- day language in his job. Visiting a place where he had spent several holidays, his wife and he noted that he had diYculties in finding familiar routes. As well as his memory problems the patient complained of a loss of libido and of a flattening of emotional reactions. He said: “There is nothing which makes me really happy or really sad. It’s all far away”. Neurological examination showed only a slight reduction of fine motor skill of the right B hand, which disappeared completely during the subsequent weeks.

NEURORADIOLOGICAL EXAMINATION Brain MRI (figure) showed a sharply demar- cated, slit-like, lesion which ran from the bottom of the left frontal horn in a slightly Cd curved way laterally. The caudal limit of the lesion was at the level of the anterior commis- sure. The lesion destroyed a large portion of CI the nucleus accumbens and encroached on the GP inferior limb of the capsula interna and the most ventral portions of the anterior nucleus caudatus and globus pallidus. There was no Acb general enlargement of ventricles, but the wall of the left frontal horn was slightly widened and DB flattened, indicating some atrophy of the head of the caudate nucleus. Tc-99-HMPAO SPECT showed hypoper- (A)T1weighted MRI of the lesion. (B) Anatomical scheme of the centre of the lesion, corresponding to the leftmost image of the bottom row of the MRI. The right side of the fusion of left basal ganglia (92% of homologu- figures corresponds to the left side of the brain. GP=globus pallidus; Cd=caudate nucleus; ous right brain region), left frontal cortex

Acb=nucleus accumbens; CI=capsula interna; DB=diagonal band. (91%) and left basal and medial temporal cor- http://jnnp.bmj.com/ lobes and which largely spared structures rich tex (91% and 90%). on cholinergic cells. NEUROPSYCHOLOGICAL EXAMINATION Attention Case report The patient scored well within the normal The patient was a 55 year old right handed range on a battery of computerised tests prob- engineer who held a managing position in an ing reaction time, speed of visual scanning, 28 international computer company. He had arte- divided attention, and shifting of attention. on September 28, 2021 by guest. Protected copyright. rial hypertension. In July 1996 he became His attention/concentration index value on the somnolent and confused. On emergency ad- WMS- R29 was 111. mission, CT showed bleeding into the anterior portion of the left basal ganglia with invasion Language into the left frontal horn of the lateral ventricle. In German, his native language, speech was No source of bleeding could be identified on well articulated, fluent, and syntactically cor- angiography. During the subsequent weeks the rect. Only when talking about diYcult and medical records noted mild right sided weak- complex matters did his expression become ness, word finding diYculties, and paraphasia. imprecise and circumstantial with occasional His ability to store new information was confusions of low frequency words. He per- severely defective and he was disoriented to fectly named 20 highly familiar items from the time. Snodgrass-Vanderwart pictures30 31 but made He was admitted as an outpatient to our two errors for 20 unfamiliar items (“perhaps a department in October 1996. The hemiparesis goose?” for ostrich, and skittle for spinning had resolved and conversation was inobstru- top). Knowledge of second languages was not sive. He was fully oriented, but complained of assessed. memory problems: He rated himself as very poor at remembering names, places, and the Intelligence content of conversations. His spouse con- On a multiple choice lexical decision test with firmed that he often enquired about details words of decreasing frequency,32 reflecting pre- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.163 on 1 August 1999. Downloaded from Basal forebrain amnesia 165

Anterograde memory

Test Result Comment Rivermead behavioural memory battery: Profile score / screening score 15 / 6 Defective WMS-R index score: Verbal memory 83 Below average Visual memory 104 Average Delayed recall 78 Below average Berlin amnesia test z scores: Verbal -3.23 Severely defective Numeric -0.12 Average Recall/recognition verbal -1.88 Below average Recall/recognition numeric -1.06 Average Recognition memory: 25 words: immediate/delayed 6 (16/10) / 5 (21/16) Severely defective (correct/false positive) 25 faces: immediate/delayed 18 (19/1) / 15 (17/2) Average (correct/false positive) CVLT: List a: 5 trials (total intrusions) 4/4/7/6/6 (1) Defective List b 5 List a: recall after interference 0 (5)/ 1 (1) Severely defective /delayed (intrusions) Delayed recognition of list a (false 14 (9) Severely defective positive) Learning of eight paired associates (4 trials): Words 0/0/2/2 Defective with exception of trial 1-3 of face-name associations Objects 2/3/4/4 Face- name (delayed after 48 5/6/7/7 (0) hours) Story recall (24 units of information): 9 / 1 Below average / severely defective immediate / delayed Story recall (16 units of information): immediate / after 30 min / after 24 hours Emotional story (with cueing) 8.5 / 0 (5) / 0 (4.5) All values severely defective Neutral story (with cueing) 3* / 0 (2) / 0 (1) Taylor figure recall: 28 / 23 Average immediate/delayed

Below average=<25th percentile; defective=<5th percentile; severely defective=<1st percentile. *After immediate recall the neutral story had been presented for a second learning trial which yielded an immediate recall score of 5. morbid intelligence level, his score was equival- Anterograde memory ent to an IQ of 124. On the German WAIS-R33 A selection of tests of anterograde memory is his performance IQ was 121 and his verbal IQ given in the table. In accordance with the was 100. In the verbal part the poorest result patient’s complaints, the reports of his spouse was on arithmetic (scaled score 6) whereas the and our findings, the Rivermead behavioural 39 other subtests yielded scaled scores between 10 memory test confirmed ecologically signifi- http://jnnp.bmj.com/ and 13. In the performance part scaled scores cant memory impairment. Recall and recogni- on picture completion and block design were tion of verbal information were severely defec- superior (18 and 15) and the other scaled tive. By contrast, recall and recognition of non- scores ranged from 10 to 12. verbal visual information were normal. On the Berlin amnesia test,40 which provides norma- Executive functions tive data for comparing recall and recognition, He obtained normal scores on the modified recognition of words seemed to be less affected 34 Wisconsin card sorting test, the Tower of than free recall. A story with emotional content on September 28, 2021 by guest. Protected copyright. London test,35 and the six elements test.36 was better recalled than a neutral one. A nota- Design fluency37 was normal (25/3 minutes: ble feature of his performance on tests of free 40th percentile of normal controls). Fluency recall of words was the production of intru- for words with a given initial letter was lower sions. For example, in recall after interference albeit still within the normal range (20/3 min- of a German adaptation of the California utes: 15th percentile). verbal learning test (CVLT)41 he produced more intrusions than list words. Likewise, the Primary and working memory poor scores on verbal recognition memory Visual span was above average (WAIS-R: were largely due to false positive responses. forwards 98th percentile; backwards 90th per- Indeed, he recognised roughly equal numbers centile) and digit span average (forwards 51st of faces and words, but whereas the total score percentile, backwards 31st percentile). A weak- on face recognition was normal, the score on ness of verbal working memory manifested verbal recognition fell to near chance levels itself in tests which demand both maintainance because of the many false positive responses. and processing of verbal information—for However, he confabulated neither in story example, reading span38 (span=2, 6th percen- recall nor in daily life. tile) or a computerised test of verbal working memory28 (level 3, 1st percentile). The poor Semantic memory result on WAIS-R arithmetic may also relate to A preservation of basic semantic knowledge this weakness. was manifested by his average score on the J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.163 on 1 August 1999. Downloaded from 166 Goldenberg, Schuri, Grömminger, et al

WAIS-R subtest information and by the duced wrong information but stated that he did absence of significant naming diYculties. not know the response. However, he did have some word finding diY- Primary memory for verbal material was culties for unfamiliar items (see above) and within normal limits. Only when he had to categorical fluency42 was mildly impaired with maintain and simultaneously process verbal the exception of musical instruments (animals: material his performance fell below normal 13/1 min; birds: 4/1 min; household items: 15/1 values. He scored normally on tests of min; musical instruments: 12/1 min). Drawing executive functions. Verbal fluency was lower familiar objects from memory was good. We than graphic fluency, and there were some could not assess his professional knowledge but word finding problems for unfamiliar items. he credibly assured us that it had become These language diYculties were, however, far severely defective. On a famous faces test too mild to plausibly explain his severe amnesia which presents faces of 15 famous persons for any verbal material. from each decade and asks for the famous per- The responsible lesion was unilaterally left sons’ names and for semantic information sided. It had its centre in the nucleus about them his scores were at the 5th percentile accumbens but encroached on the inferior limb of age matched controls for persons famous of the internal capsula and the ventral portion between 1966 to 1975, below the 1st percentile of the globus pallidus and nucleus caudatus. for 1976 to 1985, and between the 5th and There was evidence of some atrophy of the 25th percentile for 1945 to 1965 and after head of the caudate nucleus and of frontal and 1986. In this test he never produced a wrong temporal hypoperfusion. name and only once wrong semantic infor- Similar to patients with unilaterally left sided mation (“American Secretary for Foreign medial temporal or thalamic lesions4645 and AVairs” for Winston Churchill). All other two other patients with strictly unilateral left errors were constituted by “don’t know” sided basal forebrain lesions15 21 he had amnesia responses. only for verbal material and no significant defi- cits of general intelligence, attention, or execu- Autobiographical memory tive function. This constellation is unlikely to 23 The patient complained of an impoverishment be a manifestation of diVuse brain damage. of his entire autobiographical memory. On the We therefore feel justified to interprete his autobiographical memory interview43 knowl- amnesia as a sequel of the circumscribed basal edge about autobiographical facts was good for forebrain lesion. childhood and for recent time (17.5 and 18 out In addition to the anterograde memory defi- of 21) but defective for early adulthood cit, he had diYculties recalling premorbidly (11/21). Recall of autobiographical incidents acquired autobiographical and semantic infor- was borderline to abnormal for all time periods mation. As these were tested mainly verbally, it and showed a similar time gradient with the is not clear whether the deficit aVected visual most severe loss for early adulthood (child- memory as well. Drawing of objects from hood: 6/9; early adulthood: 1/9; recent time: memory was normal, but the husband and his 4/9). Recall of autobiographical episodes was wife reported some diYculties with retrieval of further explored with a modified Crovitz topographical memories. Recall of autobio- technique.44 He was presented with 60 cue graphical episodes and of famous persons was http://jnnp.bmj.com/ words (for example, train, friendship, hostility, poorest for the years from 1976 to 1985 when swim, laugh, destroy). He was asked to produce he was between 35 and 45 years old. Presum- an autobiographical episode related to each ably, the poor result for “early adulthood” in word and to say from which period of his life it the autobiographical memory interview in- stems. Episodes were rated for specifity and cluded the same period. This gap may be an richness. He produced only 35 episodes, which enhancement of the paucity of memories from is below average. In addition, he gave 12 this period of life which has been documented 46 general statements without episodic character, in normal subjects older than 50 years. on September 28, 2021 by guest. Protected copyright. and refused to produce more specific infor- If anterograde and retrograde amnesia had a mation when requested to do so. In parallel to common cause, this would be most likely to be the famous faces test, production was poorest a defect of retrieval rather than of memory for the period from 1976 to 1985. We could not consolidation or storage. There are, however, check the veracity of those episodes which he other patients with basal forebrain amnesia produced but they did seem to be plausibly in whom premorbidly acquired auto- 20 21 20 true memories. biographical and semantic memory were normal. Apparently the combination of an- terograde and retrograde memory loss is not Discussion an invariable feature of basal forebrain amne- The patient had a severe anterograde memory sia. We think, however, that the published data deficit for verbal material aVecting free recall on retrograde memory loss in basal forebrain and recognition. With both modes of testing a amnesia are too scarce too permit any definite significant source of errors was constituted by conclusions regarding their underlying mecha- false positive responses and intrusions. How- nisms. Further discussion will concentrate on ever, the patient confabulated neither on story the anterograde verbal memory deficit. recall nor in day to day memory. Retrograde The absence of a general weakness of execu- memory was impoverished for both semantic tive function does not rule out the possiblity of and autobiographical information. On tests of a specific weakness of executive control of ver- retrograde memory he virtually never pro- bal memory. We discuss this possibility, and J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.163 on 1 August 1999. Downloaded from Basal forebrain amnesia 167

then the location of the critical lesion within central position in the functional interplay the basal forebrain. between these components of the basal fore- brain and between the basal forebrain and FALSE RESPONSES AND STRATEGIC CONTROL OF other brain regions. It constitutes a junction MEMORY RETRIEVAL between extended amygdalae and the ventral The patient produced numerous intrusions in striatopallidal system and it has eVerent recall of word lists, and the inaccuracy of his connections to the corticopetal system. It is recognition memory for words was entirely due therefore able to modulate cholinergic to the high number of false positive responses. output.47 48 The nucleus accumbens sends At the same time, he confabulated neither on eVerents to the hypothalamus, substantia story recall, nor in recall from remote semantic nigra, autonomic brainstam nuclei, and the and autobiographical memory, nor in daily life. pallidum, which provides a connection to the False responses were thus restricted to memory dorsomedial nucleus of the thalamus.49 It for word lists. For these words, the decision receives aVerent projections from dopaminer- whether a word coming to mind during recall gic midbrain nuclei and intralaminar thalamic was correct or not could be based on nothing nuclei, from the hippocampus and basolateral else but on memory of this particular word’s amygdalae, and from the prefrontal, insular, occurrence in the word list. There was no way and temporal association cortex.47 50–52 It is thus to infer the plausibility of the decision from in a position to integrate inputs from multiple partial recall of the memorised material or cortical and subcortical areas including the from preserved remote memory. By contrast, hippocampus and the amygdalae, and to exert tests which did not provoke false responses modulatory influences on widespread cortical asked either for memory of organised verbal function. information (story recall, autobiographical epi- Animal studies have suggested a role of the sodes), or for recall of names and information nucleus accumbens in memory. Rats with with a defining relation to pictures presented selective lesions of the nucleus accumbens have during recall (famous persons). In these tests, been found to fail on tests such as the Morris he could exploit partial recall of the memorised water maze or delayed win-shift foraging, material or preserved remote memory for which depend on mnemonic function and judging the plausibility of information coming which are known to be sensitive to hippocam- to mind. pal lesions.51 53–55 It has not, however, been set- On this account, supervisory control of recall tled whether these deficits are reflections of was intact. He used available knowledge for mnemonic dysfunction or of other behavioural controlling the plausibility of information disturbances.50 56 coming to mind. The source of false responses Published studies of basal forebrain amnesia might be sought in a general enhancement of lend credibility to a role of the nucleus “feeling of familiarity”24 which levelled the sig- accumbens in human memory. In a group nal to noise ratio between memorised items study of patients with operated anterior and items which were similar but had not been communicating artery aneurysms, Irle et al17 presented. Feelings of familiarity were assigned found memory disturbances only in patients indistinctly to any word that came to mind with “combined basal forebrain-striatum” le-

during recall and misled his responses when he sions. The nucleus accumbens forms part of http://jnnp.bmj.com/ had no external evidence for checking the the ventral striatum. Nucleus accumbens credibility of this feeling. False responses may lesions were visible on MRI or CT in several also have resulted from a strategic decision at published cases of basal forebrain the level of supervisory control. He may have amnesia.12–14 18 20 In a further patient15 the lesion opted for a liberal response bias whenever he aVected the ventral pallidum and in two other had no resources for estimating the plausiblity patients MRI showed atrophy of the caudate of responses. In any case, intrusions and false nucleus.21 22 It is notable that in some of these 13 15 21 22 positive responses do not indicate a failure of cases, as well as in our patient, the on September 28, 2021 by guest. Protected copyright. supervisory control of memory. nucleus basalis, septum, and diagonal band, which have the greatest concentration of corti- IS THE NUCLEUS ACCUMBENS A CRITICAL copetal cholingergic cells, seem to be unaf- STRUCTURE FOR HUMAN MEMORY? fected. The basal forebrain consists of three function- In summary, there seems to be rather ally distinct compartments47: the corticopetal, convincing evidence that aVection of parts of mainly cholinergic, system, the extended amyg- the striatopallidal system makes an important dalae, and the ventral striatopallidal system. contribution to basal forebrain amnesia.17 The Cholinergic cells are concentrated in the evidence for the nucleus accumbens as critical septum, the diagonal band, and the nucleus structure is less unequivocal, but does seem to basalis.48 The extended amygdalae stretch from deserve further studies in animals and the centromedial nuclei of the amygdalae humans.51 medially and rostrally through the substantia Because the patient’s lesion encroached on innominata into the medial portion of the the anterior limb of the internal capsula our nucleus accumbens where they join the ventral finding would be compatible with the hypoth- striatopallidal system. The ventral striatopalli- esis that lesions of fibre tracts rather than cell dal system is constituted rostrally by the bodies are responsible for amnesia from extra- nucleus accumbens and caudally by subcom- hippocampal lesions.15 27 In particular, the cap- missural continuations of putamen and globus sular lesion may have damaged the anterior pallidus. The nucleus accumbens occupies a thalamic peduncle which connects the dorso- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.67.2.163 on 1 August 1999. Downloaded from 168 Goldenberg, Schuri, Grömminger, et al

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only 20% in one study, but the specificity was twice a day, always with his neck in extreme excellent (100%).2 The sensitivity was con- retroflexion. LETTERS TO siderably better in the hands of Auer et al,1 General physical examination (8 hours but in this study the specificity (true negative after onset of symptoms) was normal. Neuro- THE EDITOR rate in subjects free of disease) was not logical examination showed minimal paresis considered because all patients had vertebral and impaired dexterity of the right hand, mild artery dissection. The following case report circumduction of the right leg, and an illustrates that care must be taken to avoid insecure tandem gait. An MRI (including T1 false positive results when using MRA for the weighted spin echo images with and without Magnetic resonance imaging and diagnosis of vertebral artery dissection. fat suppression, and proton density and T2 vertebral artery dissection A 47 year old male pilot suddenly experi- weighted fast spin echo sequences, performed enced clumsiness and slight loss of strength in on a 1.5 Tesla whole body MRI system) per- Since the advent of advanced radiological the right arm and leg during a long distance formed several hours later visualised both a modalities such as MRI and magnetic flight, while he stooped forward. During the fresh and an old right sided cerebellar infarct resonance angiography (MRA), dissections (figure A). In addition, MRI showed an following hours, he developed a global head- of cervical arteries are increasingly recog- irregular right vertebral artery in which a pat- ache without irradiation to the neck, but the nised as a common cause of stroke in young ent lumen was partially surrounded by a 1 other symptoms gradually diminished. Prior adults. Auer et al recently advocated MRA as semilunar area of high signal intensity on T1 the initial diagnostic tool for vertebral artery history was unremarkable, except for a 3 hour and T2 weighted images. On fat suppressed dissection. Conventional angiography might period of horizontal diplopia which suddenly images, this area’s high signal intensity be avoided altogether in subjects with a developed 3 months earlier. He had never persisted, excluding the possibility that it suspicious history and MRA images sugges- smoked. Family history was negative for originated from perivascular fat. This image tive of a dissection (double lumen or mural cardiovascular disorders. The patient later was suggestive of mural haematoma due to 1 haematoma). The sensitivity of MRA for the confessed that he had recently picked up the vertebral dissection (figure B). Because we diagnosis of vertebral artery dissection was habit of gargling his throat with toothpaste were reluctant to base any treatment deci- sions (anticoagulants) merely on MRI find- ings, digital subtraction angiography was per- formed on the day of admission. This examination was normal (figure C). Shortly after this procedure, the patient developed vertigo and nystagmus which disappeared after 3 hours. Because we were puzzled by the discrepant findings on conventional angio- graphy and MRI, we performed an MRA 4 days later. At this examination, the semilunar area of high signal intensity was found again (figure D), despite saturation of craniofugal and craniopetal flow respectively, which was applied to exclude the possibility that the high signal originated from flow in the periarterial venous plexus. Therefore, this examination was again suggestive of right vertebral artery dissection. An extensive search for other causes of stroke showed no abnormalities. Hence, due to the continuing discrepancy between conventional angio- graphy and MRI/MRA, and due to the absence of any other cause of stroke, no cer- tain diagnosis could be established. In this patient, a diagnosis of right vertebral artery dissection was initially made given the clinical course with repeated episodes of ischaemia restricted to the vertebrobasilar system, as well as the suggestive MRI findings.1 We speculated that habitual gar- gling was a potential underlying cause, as neck retroflexion can cause cervical dissec- tions. However, we had to reject this diagno- sis in view of the normal conventional angio- graphy, which remains the gold standard for diagnosing cervical artery dissection.3 In one series,2 conventional angiography was never falsely negative in patients with clinical signs or symptoms of vertebral artery dissection. The possibility that conventional angio- graphy had nevertheless yielded a false nega- tive result seems highly unlikely. In dissected arteries, MRI/MRA can detect intimal flaps, mural haematomas, or aneurysmal dilata- tions that are sometimes missed by conven- tional angiography, but even in such patients conventional angiography is never completely normal in the acute stage. Follow up examinations of patients with proven verte- (A) T2 weighted fast spin echo image showing high signal intensity in the right cerebellar hemisphere, bral artery dissection indicate that the indicative for a recent infarct. The older infarct cannot be seen on this section. (B) Axial T1 weighted appearance of a dissected artery on conven- fast spin echo image with fat saturation at the level of the base of the tongue, showing a semilunar tional angiography can normalise in a sub- area with high signal intensity around the flow void in the right vertebral artery. (C) Selective contrast injection in the right vertebral artery shows no abnormalities. The remainder of the stantial proportion of patients, but always intra-arterial angiography of the cervical and cranial arteries was also normal. (D) Axial three after an interval of at least 1 to (usually) sev- dimensional time of flight technique, acquired in the axial plane image at the same level showing high eral weeks.1 Conventional angiography in our signal intensity at the same location as in B. patient was performed on the day of admis- 692 Letters, Correspondence, Book reviews, Correction sion, directly after the “abnormal“ MRI and 2 Levy C, Laissy JP, Raveau V, et al. Carotid and was no benefit. Electroconvulsive therapy was four days prior to the “abnormal“ MRA, vertebral artery dissections: three-dimensional proposed by a psychiatry consultant but was time-of-flight MR angiography and MR imag- hence spontaneous resolution of the dissec- ing versus conventional angiography. Radiology refused by the patient’s family. The clinical tion is very unlikely. Therefore, we consider 1994;190:97–103. picture was dominated by an akinetic mutism our MRI/MRA examinations falsely positive, 3 Hart RG. Vertebral artery dissection. Neurology with marked catatonia. Catatonia due to and we hypothesise that the area of semilunar 1988;38:987–9. 4 Miaux Y, Cognard C, Martin-Duverneuil N, et CPEM was considered. A repeat MRI 12 high signal intensity originated from a al. Flow related enhancement in the vertebral days after the onset of symptoms showed high perivascular venous plexus, in which we were plexus mimicking an intramural hematoma. intensity areas in the pons, caudate, and unable to saturate inflow of blood completely, Am J Neuroradiol 1996;17:191–2. putamen consistent with CPEM (figure A, 5 Dumas JL, Stanescu R, Goldlust D, et al. Verte- presumably due to extremely slow flow. bral vein imaging with MR angiography. Am J B). Physical and occupational therapy were Our “pilot study“ illustrates the specificity Neuroradiol 1997;18:1190–2. instituted and she gradually recovered over problems of MRI/MRA for the diagnosis of the next 2 weeks. She was transferred to a vertebral artery dissection. Two anatomical rehabilitation hospital where she recovered Catatonia due to central pontine and structures surrounding vertebral arteries con- completely and returned to live independ- tribute to these problems. The first structure extrapontine myelinolysis: case report ently. She has been followed up at the neurol- is the venous plexus that surrounds vertebral ogy clinic and has not shown any residual Central pontine and extrapontine myelinoly- arteries. This structure may have a semilunar deficits. sis (CPEM) are recognised complications of appearance, and slow flow in its lumen may CPEM usually presents with tetraparesis give rise to high signal intensity on both MRI hyponatraemia and its overly rapid 1 and pseudobulbar palsy. Unusual clinical and MRA, creating an image suggestive of correction. CPEM usually presents with 1 presentations include extrapyramidal syn- dissection.45It has been suggested that satu- spastic tetraparesis and pseudobulbar palsy. dromes, ataxia, and neurobehavioural syn- ration slabs in conjunction with MRA We describe a patient with CPEM in whom dromes. Although psychiatric manifestations completely suppress flow related high signal, behavioural manifestations overshadowed of CPEM have been recognised they usually thus distinguishing it from high signal from corticospinal tract signs. manifest as an agitated delirium, or a an intramural haematoma which cannot be A 64 year old Chinese speaking woman pseudobulbar state with pathological laugh- suppressed by saturation slabs.45The present with a history of episodic psychotic ing and crying.1 When present, neuropsychi- case report illustrates that flow in this plexus depression that had never required admis- atric symptoms are usually overshadowed by cannot always be suppressed. sion to hospital was admitted to a hospital florid signs of brainstem and pyramidal tract The second tissue that may falsely present because of vomiting and diarrhoea. Her gen- dysfunction.23 Behavioural changes such as as a dissection is fat that directly surrounds eral and neurological examination were nor- vertebral arteries. This fat also gives rise to mal. On admission she had a sodium inappropriate aVect, emotional lability, per- high signal intensity, but using fat suppres- concentration of 105 meq /l. An infusion of sonality changes, paranoia, poor judgement, 3% saline at a rate of 150 ml/ hour was given emotional incontinence, and disinhibition sion techniques it can be readily diVerenti- 12 ated from intramural haematoma. Further- during 6 hours. Ten hours later her sodium have been reported. Price and Mesulam more, the usual diameter asymmetry of was 134 meq/l and she was mute and described a case of pontine myelinolysis in vertebral arteries, turbulence and magnetic tetraparetic. She seemed catatonic with which transient pyramidal signs were fol- motor perseveration. Transfer to our hospital lowed by confusion, restless behaviour, pres- susceptibility near sharp vessel turns can also 2 cause false positive MRA results.2 In some was requested. sured tangential speech, and disinhibition. patients, MRI cannot distinguish between On admission her vital signs were normal. Our patient also had transient long tract signs intraluminal thrombus and intramural hae- She was mute without any spontaneous voli- but they were followed by a catatonic state. matoma, leading to false conclusions. tional movements except for visual pursuit. The extensive extrapontine myelinolysis Decisions based on false positive MRI/ She was tetraparetic and hyperreflexic with present in our patient may explain the behav- MRA results can be hazardous due to the increased tone and bilateral Babinski’s signs. ioural symptoms we encountered. sometimes severe side eVects of anticoagu- CPEM was suspected. Admission MRI, CPEM may present with unusual behav- lants, the treatment that is recommended by EEG, and spinal fluid examination were nor- ioural symptoms. At the onset of neurological some to prevent further ischaemic events. mal. Over the next 2 days the reflexes deterioration MRI may be normal but subse- Another danger of a false positive diagnosis of normalised and the Babinski’s signs disap- quent imaging studies usually disclose the vertebral dissection is that it may preclude the peared but she continued to have mild diffuse lesions. CPEM presenting with neuropsychi- search for other causes of stroke that could be weakness. She had waxy flexibility and atric symptoms in patients with normal initial amenable to secondary prevention. assumed bizarre non-physiological postures imaging studies might suggest a psychogenic MRI/MRA remains important because it consistent with catatonia. Psychogenic unre- aetiology. Corticospinal tract signs may be helps visualise ischaemic lesions and, in some sponsiveness was suspected and she was temporary. A strong index of suspicion for patients, provides complementary morpho- started on risperidone and sertraline. There CPEM is required when patients with recent logical information to cerebral angiography.1 Furthermore, it is a non-invasive procedure, an important advantage over cerebral angio- graphy which carries a morbidity and mor- tality risk. Our patient, who developed transient neurological deficits shortly after angiography, underscores this. Therefore, MRA can play a part in the diagnosis of ver- tebral artery dissection, provided that the pit- falls mentioned above are recognised to avoid false positive results. In case of doubt, cerebral angiography remains the gold stand- ard for vertebral artery dissection. B R BLOEM G J LAMMERS Department of Neurology M A VAN BUCHEM Department of Radiology, Leiden University Medical Centre, The Netherlands Correspondence to: Dr Bastiaan R Bloem, Depart- ment of Neurology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Neth- erlands. Telephone 0031 71 5262134; fax 0031 71 5248253; email [email protected]

1 Auer A, Felber S, Schmidauer C, et al. Magnetic resonance angiographic and clinical features of (A) Axial T2 weighted image showing prominent high signal intensity within the pons suggestive of extracranial vertebral artery dissection. J Neu- central pontine myelinolysis. (B) Axial T2 image showing symmetric bilateral areas of high signal in rol Neurosurg Psychiatry 1998;64:474–81. the caudate and putamen suggestive of extrapontine myelinolysis. Letters, Correspondence, Book reviews, Correction 693 hyponatraemia present with behavioural counts of those in the hippocampus and sample size was small, there were not even changes. Akinetic mutism and catatonia may superior temporal gyrus. Genotypes of BCHE trends for a positive association in our study, be the dominant clinical features in CPEM. and ApoE in all patients were determined as suggesting that the lack of association was not 12 JULIO CHALELA described elsewhere. Genotypic and allelic due to small sample size. The frequency of 2 JORGE KATTAH distributions of BCHE were analysed by ÷ BCHE-K in our Japanese control population Department of Neurology, Georgetown University test. The densities of the SPs, NPs, and was 0.18. This was not significantly diVerent Medical Center, Washington DC, USA NFTs, and ages at onset and durations of ill- from that in the British population examined Correspondence to: Dr Julio Chalela, 4000 Presi- ness were compared among BCHE genotypes by Russ et al (0.20).3 However, the frequency dential Boulevard, Apartment 213, Philadelphia, PA with the Kruskal-Wallis test or Mann- of BCHE-K in the British control population 19131, USA. Telephone 001 215 878 3311; Whitney U test in total subjects, those with reported by Lehmann et al was 0.09, which email:[email protected] Alzheimer’s disease, and non-demented sub- was significantly lower than our results jects. We also examined these relations in the (p=0.04).1 These findings indicate that the 1 Illowsky B, Laureno R. Pontine and extrapon- subgroups divided by the ApoE å4 status or frequency of BCHE-K and its genetic linkage tine myelinolysis. Pontine and extrapontine myelinolysis: a neurologic disorder following the age of 75 years. Statistical significance was with the development of Alzheimer’s disease rapid correction of hyponatremia. Medicine defined as two tailed probabilities of <0.05. would be diVerent among sample popula- 1993;72:359–73. There were no significant diVerences in the tions. 2 Price BH, Mesulam MM. Behavioral manifesta- frequency of BCHE-K genotypes or alleles tions of central pontine myelinolysis. Arch Neu- Our neuropathological study disclosed a rol 1987;44:671–3. between patients with Alzheimer’s disease significant association of BCHE-K with 3 Laureno R, Illowsky B. Myelinolysis after (0.16 in allele frequency) and non-demented Alzheimer type neuropathological changes in correction of hyponatremia. Ann Intern Med subjects (0.18), and in the total subjects, 1997;126:57–62. the ApoE å4 carriers older than 75 years, but ApoE å4 carriers or non-ApoE å4 carriers, not in the non-ApoE å4 carriers. Lehmann et although a strong association of ApoE å4 al showed that BCHE-K was strongly associ- Association between butyrylcholin- alleles with Alzheimer’s disease was found in ated with the development of Alzheimer’s esterase K variant and the Alzheimer this population (p=0.004). Genetic associ- disease in the ApoE å4 carriers older than 75 type neuropathological changes in ation of BCHE-K genotypes with sporadic years.1 Analyses of the same subgroup of apolipoprotein E å4 carriers older than Alzheimer’s disease was non-significant in all ApoE å4 carriers older than 75 years subjects older than 75 years, the ApoE å4 75 years increased statistical significance in both our carriers older than 75 years, and non-ApoE studies and that of Lehmann et al. This Apolipoprotein E (ApoE) å4 has a strong å4 carriers older than 75 years. There was no suggests that BCHE-K as a genetic marker is influence on the development of sporadic genetic association of BCHE-K with the den- linked with formation of Alzheimer type neu- Alzheimer’s disease in many ethnic popula- sities of the SPs, NPs, or NFTs in the ropathological changes or development of hippocampus and superior temporal gyrus in tions. However, ApoE å4 is neither necessary Alzheimer’s disease in the ApoE å4 carriers nor suYcient for the development of the total subjects, in the Alzheimer’s disease older than 75 years. However, a decrease of or non-demented groups, or with ages at Alzheimer’s disease, suggesting that other the severity of Alzheimer type neuropatho- onset or duration of illness in Alzheimer’s genes increase the risk of Alzheimer’s disease. logical changes with BCHE-K in our study disease. However, when we divided total sub- One such new candidate is the butyrylcho- was not expected because Lehmann et al 1 jects into two subgroups with diVerent ApoE linesterase (BChE) gene (BCHE). BChE is showed an increase in frequency of the å4 status, there was significant association associated with senile plaques (SPs) and neu- BCHE-K allele in Alzheimer’s disease.1 Sin- between BCHE-K and the density of the SPs rofibrillary tangles (NFTs). Lehmann et al gleton et al also reported that BCHE-K was recently reported that the K variant of BCHE and NPs in the superior temporal gyrus(STG) in the ApoE å4 carriers (SPs, not associated with the densities of the SPs (BCHE-K) was associated with the develop- and NFTs, even in the ApoE å4 carriers.4 In ment of Alzheimer’s disease, especially in p=0.04; NPs, p=0.03, data not shown). Fur- addition, BCHE-K was not related to the ApoE å4 carriers older than 75 years.1 A pos- ther, we analysed the correlation between and the densities of the SPs, NPs, development of Alzheimer’s disease in the sible mechanism as to how BCHE-K is BCHE-K 3 ApoE å4 carriers in our study. Russ et al and related to Alzheimer’s disease under the and NFTs in the hippocampus and superior Singleton et al4 also showed a lack of influence of ApoE å4 is the acceleration of temporal gyrus in the ApoE å4 carriers older association between and the devel- Alzheimer type neuropathological changes. If than 75 years and non-ApoE å4 carriers older BCHE-K opment of Alzheimer’s disease. However, BCHE-K has an eVect on the development of than 75 years (table). There was a significant Alzheimer’s disease in ApoE å4 carriers, the genetic association of BCHE-K with the den- Hiltunen et al showed that BCHE-K had a formation of Alzheimer type neuropathologi- sities of the SPs, NPs, and NFTs in the STG protective eVect on the development of cal changes may be accelerated by in the ApoE å4 carriers older than 75 years. Alzheimer’s disease in ApoE å4 carriers BCHE-K 5 in the ApoE å4 carriers. There was a decrease of severity of Alzheimer younger than 75 years. The eVects of We have examined genotypes of BCHE and type neuropathological changes with BCHE- BCHE-K on the Alzheimer type neuropatho- ApoE, and densities of the senile plaques K. A similar trend was seen in the hippocam- logical changes or development of (SPs), with dystrophic neurites (NPs), and pus though this did not reach significance. Alzheimer’s disease are diVerent among neurofibrillary tangles NFTs in the brains Our results showed that BCHE-K might studies, suggesting that the significant genetic from 51 patients with Alzheimer’s disease and have no eVect on the development of sporadic association in the studies by Lehmann et al,1 90 non-demented subjects from a postmor- Alzheimer’s disease even in the ApoE å4 car- Hiltunen et al,5 and ourselves might be tem series of Japanese. Clinical and postmor- riers or subjects older than 75 years. By con- linkage disequilibrium with relevant variabil- tem diagnosis of Alzheimer’s disease was car- trast with a significant genetic association in ity in BCHE or other adlacent gene on chro- ried out as described previously.2 The patients confirmed at postmortem in the mosome 3, and that BCHE-K does not play a densities of Alzheimer type neuropathologi- British population,1 there was no correlation direct part in the pathogenesis of Alzheimer’s cal changes were quantified by averaging the in the Japanese population. Although our disease. BCHE genotypes and the densities of the SPs, NPs and NFTs in the hippocampus and superior temporal gyrus in ApoE å4 carriers older than 75 years and non-ApoE å4 carriers older than 75 years

ApoE å4 carriers over 75 years (n=28) non-ApoE å4 carriers over 75 years (n=95)

BCHE genotype K/N (n=8) N/N (n=20) p K/K (n=4) K/N (n=25) N/N (n=66) p

Hippocampus: SPs 3.0 (0.0, 17.2) 12.2 (4.5, 28.7) 0.13 0.0 (0.0, 5.7) 0.0 (0.0, 16.7) 0.0 (0.0, 10.3) 0.69 NPs 0.7 (0.0, 11.9) 11.0 (3.9, 25.3) 0.07 0.0 (0.0, 3.5) 0.0 (0.0, 14.0) 0.0 (0.0, 8.6) 0.63 NFTs 1.1 (0.4, 23.1) 17.4 (2.5, 59.6) 0.12 3.9 (0.9, 10.0) 7.0 (0.6, 35.7) 4.6 (0.4, 15.0) 0.72 Superior temporal gyrus: SPs 0.2 (0.0, 22.8) 49.7 (12.1, 83.8) 0.007 0.0 (0.0, 58.0) 6.0 (0.0, 64.8) 1.2 (0.0, 44.0) 0.61 NPs 0.2 (0.0, 8.8) 10.7 (3.6, 19.0) 0.02 0.0 (0.0, 3.7) 2.0 (0.0, 6.5) 0.4 (0.0, 7.8) 0.59 NFTs 0.0 (0.0, 0.2) 0.9 (0.0, 4.9) 0.04 0.0 (0.0, 0.0) 0.0 (0.0, 0.5) 0.0 (0.0, 0.4) 0.32

Values are medians (25th percentile, 75th percentile). The density represents the average counts in 2.56 mm2 for the SPs and NPs, and in 0.64 mm2 for the NFTs. BCHE=butyrylcholinesterase gene; ApoE=apolipoprotein E; K=the K variant allele of butyrylcholinesterase gene; N = the normal allele of butyrylcholinesterase gene; SPs =senile plaques; NPs=senile plaques with dystrophic neurites; NFTs=neurofibrillary tangles. 694 Letters, Correspondence, Book reviews, Correction

We are grateful to I Isahai, M Takeda, H Konuma, The patient was a 71 year old, retired phy- “Honey PLEASE!” with loudness, stress, and Y Miura for their expert technical assistance. sician witha3to4yearhistory of memory accentuation of the word “please,” and as if The study was supported in part by a Health Science Research Grant to MY from the Ministry of impairment. Neuropsychological evaluation he really meant it. If he failed (the words were Health and Welfare, Japan and a Grant-in-Aid for disclosed a high average to superior general read without the acoustical features ex- Scientific Research to MY from the Ministry of intellectual functioning, with mild impair- pected), the patient was asked to imitate the Education, Science, Sports and Culture, Japan. ment in naming to confrontation and epi- experimenter’s reading of the word(s) or sen- N SODEYAMA sodic memory for visual and verbal memory. tence which incorporated the appropriate M YAMADA His visuospatial ability remained relatively prosodic elements only after he was asked to H MIZUSAWA unimpaired and was rated as average for his describe the aVective prosodic quality of the Department of Neurology age. His comprehension for verbal and phrase to ensure good comprehension. Five Y ITOH written instruction remained intact. At the age matched normal healthy controls volun- E OTOMO present time he is still well oriented to time teered to read the items found in the table, Department of Internal Medicine, Tokyo Medical and and place, and is somewhat independent in and in each case, read spontaneously the Dental University, Tokyo, Japan activities of daily living. He is, remarkably, word or phrase with appropriate and ex- N SUEMATSU not depressed, but does, repeatedly, raise pected prosody. Department of Pathology, Yokufukai Geriatric concern regarding the “burden he has The patient was unable to read any words Hospital, Tokyo, Japan become to his wife.” Moreover, mild hypop- or sentences with normal (appropriate and M MATSUSHITA erfusion in the frontotemporal lobes bilater- expected) prosody. Indeed, the patient had Department of Neuropathology, Tokyo Institute of ally was seen on SPECT investigation and no lost his ability to “act.” The patient’s use of Psychiatry, Tokyo, Japan evidence of pathognomonic laboratory re- prosody did, however, improve dramatically Correspondence to: Dr Masahito Yamada, Depart- sults were found. Taken together, the pattern with imitation. That is, he was able to repeat ment of Neurology, Tokyo Medical and Dental of episodic memory and naming impairments eight of the 10 items in the table with appro- University, Yushima 1–5–45, Bunkyo-ku, Tokyo and functional imaging findings was thought priate and expected prosody. Interestingly, 113–8519, Japan. Telephone 0081 3 5803 5234; fax to be consistent with the early stages of the single item that he continued to have 0081 3 5803 0169; email m-amada.nuro@ dementia of the Alzheimer’s type (DAT) in trouble producing was item three (You med.tmd.ac.jp keeping with National Institute of Neurologi- know . . .there was a time when . . .). He could cal and Communicative Disorders not pause after the words “you know” Association-Alzheimer’s Disease and Related suggesting that this patient seems to also have 1 Lehmann DJ, Johnston C, Smith AD. Synergy 6 between the genes for butyrylcholinesterase K Disorders Association criteria. The patient features characteristic of motor aprosodia. variant and apolipoprotein E4 in late-onset was consequently referred to our department Hence, because he had available the knowl- confirmed Alzheimer’s disease. Hum Mol Genet for “prospective memory book training” and edge to successfully select and use appropri- 1997;6:1933–6. follow up assessments to index progression of ate prosody, but failed to produce prosodic 2 Sodeyama N, Itoh Y, Suematsu N, et al. Presenilin 1 intronic polymorphism is not asso- disease. speech to command, dysfunction of the ciated with Alzheimer type neuropathological During our sessions his wife had stated that praxis production system is implied rather changes or sporadic Alzheimer’s disease. J the patient could no longer “act” and than the conceptual system.3 Thus, ideomo- Neurol Neurosurg Psychiatry 1998;64:548–51. complained that her once “flamboyant” and tor prosodic apraxia can be defined as an 3 Russ C, Powell J, Lovestone S, et al. K variant of butyrylcholinesterase and late-onset “unblushing” husband could no longer “put inability to produce prosody to command Alzheimer’s disease. Lancet 1998;351:881. any feeling into his lines” when they read play during speech. The precise underlying 4 Singleton AB, Smith G, Gibson AM, et al.No scripts together. She thought that he had mechanism(s)] responsible for producing this association between the K variant of the “lost his enthusiasm to act” consequent to his deficit is unknown, although Heilman et al7 butyrylcholinesterase gene and pathologically 8 confirmed Alzheimer’s disease. Hum Mol Genet new found memory loss and an “understand- and Tucker et al have hypothesised that the 1998;7:937–9. able depressive reaction.” It became clear, right hemisphere is indeed dominant for 5 Hiltunen M, Mannermaa A, Helisalmi S, et al. however, that the patient was remarkably not organising the aVective-prosodic components Butyrylcholinesterase K variant and apolipo- depressed and that he maintained normal of language and gestural behaviour and that protein E4 genes do not act in synergy in Finn- ish late-onset Alzheimer’s disease patients. prosodic speech during conversation. When the functional anatomical organisation of Neurosci Lett 1998;250:69–71. asked to use prosody to command when aVective language in the right hemisphere was reading script, however, this once gallant analogous to the organisation of proposi- actor spoke without melody, loudness, stress, tional language in the left (non-dominant) Ideomotor prosodic apraxia nor accent, with inappropriate pauses. To hemisphere. Conceptually, therefore, evi- quantify this patient’s peculiar deficit, the dence of poor aVective prosody to command Prosody is a non-verbal or suprasegmental patient was required to read and repeat words yet normal spontaneous aVective prosody, feature of language that conveys various levels and sentences to prosodic command and and good aVective prosodic repetition and of information to the listener, including imitation. Observation revealed five single comprehension would suggest a “transcorti- linguistic, aVective (attitudinal and emo- 2 1 words and five sentences that the patient cal motor aprosodia.” Note however, that the tional), dialectical, and idiosyncratic data. often and spontaneously uttered with normal patient’s spontaneous prosody was unaf- The acoustical features underlying prosody prosody, such as “Honey, PLEASE(!).” fected whereas spontaneous speech is af- include pitch, intonation, melody, cadence, These 10 items were used to assess the fected by a transcortical motor aphasia. loudness, timbre, tempo, stress, accent, and 2 patient’s ability to produce prosody to Hence, we might place the critical lesion for pauses. These acoustical features are typi- command and imitation (table). For exam- prosodic apraxia in the right dorsolateral cally spared in patients with cortical demen- ple, the patient was told to read the words frontal lobe, extending into the deep frontal tias such as Alzheimer’s disease in which temporoparietal cortices are primarily af- fected. Patients with Alzheimer’s disease, Ten item prosodic apraxia scale* however, often develop apraxia, which can be defined as a disorder of skilled movement not Script to be read Type of emphasis caused by weakness, akinesia, deaVerenta- tion, abnormal tone or posture, movement 1. Honey PLEASE ! Accentuate PLEASE ! disorders (such as tremor or chorea), intellec- 2. Are you hungry? Rise in pitch tual deterioration, poor comprehension, or 3. You know...... there was a time when I could Pause after “You know” uncooperativeness.3 Moreover, subtypes of recite all the streets in my neighborhood apraxia have been delineated and are defined 4. Holy COW ! With surprise by the nature of errors made by the patient 5. YUP, yup, yup, yup, yup... As if you were distressed with decenting intonation and stress and the means by which these errors are 6. La de da da... With melody 45 elicited. Accordingly, a patient with prob- 7. O Canada, our home and native land... With proper tempo, as if you were singing able dementia of the Alzheimer’s type is 8. SHIT ! As if you were frustrated and upset described who had normal prosodic elements 9. Thank you As if you sincerely meant it to his spontaneous everyday speech, but 10. May I go to the bathroom, I really need to go As if you really meant it, accentuating the word could not produce the same acoustical quite badly... “REALLY” features underlying prosody to command. Directions: Read the above word[s] and sentences as if you really mean them. Pretend you are auditioning The nature of his errors might constitute for a play and you are required to read the lines with the type of emphasis noted beside each line. what can be termed “ideomotor prosodic *These items were selected based on observation of the patients spontaneous speech. Therefore, they are apraxia.” qualitatively constructed and should not be used as a general measure of prosodic apraxia with all patients. Letters, Correspondence, Book reviews, Correction 695 white matter, in keeping with typical domi- The rating scale used to evaluate maximal daytime and during sleep.24We suspect that nant hemispheric lesions producing transcor- abduction of the vocal cords during larygofi- the VCAP in patients with SCA1 may be tical motor aphasia. This speculation is broscopy was as follows: (-)=normal; dominantly paralytic, because the nucleus supported by the patient’s SPECT findings of (+)=median position; (++)=paramidline po- ambiguus is sometimes pathologically in- mild hypoperfusion in the frontotemporal sition; (+++)=midline position. For the volved in SCA1 and because stridor in our lobes bilaterally. evaluation of VCAP, we tried the respiratory patients with SCA1 was more marked in 5 KONSTANTINE K ZAKZANIS flow volume loop study as well in one patient sleep. Department of Psychology, Division of Life Sciences, (patient 2) in whom maximal abduction of Our laryngofibroscopic findings suggested University of Toronto, Canada the vocal cords was slightly limited (+) on that severe VCAP caused breathing diYculty Correspondence to: Dr Konstantine K Zakzanis, laryngofibroscopy. on inspiration in the patients with SCA1 by Department of Psychology, Division of Life Sci- The correlations between VCAP and CAG obstructing the airway. Moreover, the stridor ences, University of Toronto, 1265 Military Trail, repeat length or duration of illness were ana- during wakefulness as well as sleep indicated Toronto, Ontario, Canada M1C 1A4. email lysed with the non-parametric Mann- it to be very serious. The important question [email protected] Whitney U test. concerns when tracheostomy should be The clinical features, including the vocal carried out after the diagnosis of VCAP to 1 Monrad-Krohn GH. The third element of cord findings, are summarised in the table. prevent respiratory abnormalities leading to speech: prosody and its disorders. In: Halpern VCAP was present in five of the seven sudden death. Although we consider tracheo- L, ed. Problems in dynamic neurology. Jerusalem: patients with SCA1. Although it is diYcult to stomy at the stage when breathing diYculty Hebrew University Press, 1963:101–18. 2 Ross E. The aprosodias. In: Feinberg TE, Farah know when the VCAP first became manifest on inspiration or stridor during wakefulness MJ, eds. Behavioral neurology and neuropsychol- in each patient, patient 1 showed VCAP con- is noted, it awaits further study with a large ogy. New York: McGraw-Hill, 1997:699–709. firmed by laryngofibroscopy only 2 years number of patients to decide which stage is 3 Heilman KM, Rothi LJG. Apraxia. In: Heilman after the onset of gait disturbance. KM, Valenstein E, eds. Clinical neuropsychology. best for tracheostomy. 3rd ed. New York: Oxford University Press, All five patients with VCAP showed mild Furthermore, we now consider endoscopic 1993. dysphagia requiring no tube feeding, and four cord lateralisation as another possible man- 4 Rothi LJG, Heilman KM. Apraxia: the neuropsy- patients had a history of stridor at night. agement for VCAP. chology of action. East Sussex, UK: Psychology Press, 1997. Patient 1 showed VCAP accompanying dysphagia without stridor at night even in an T SHIOJIRI 5 Roy EA. Hand preference, manual asymmetries T TSUNEMI and limb apraxia. In: Elliot E, Roy EA, eds. early stage of the disease. The VCAP was Manual asymmetries in motor performance. Boca T MATSUNAGA Raton: CRC Press, 1996:215–36. found to be severe on laryngofibroscopy in all Department of Neurology, Asahi General Hospital, 6 McKhann G, Drachman D, Folstein M, et al. three patients with breathing diYculty on Chiba, Japan Clinical diagnosis of Alzheimer’s disease: re- inspiration. Patient 5, who had the severest H SASAKI port of the NINCDS-ADRDA work group VCAP, developed stridor during wakefulness under the auspices of the Department of I YABE Health and Human Services Task Force on as well. In patients 4 and 5, the breathing dif- K TASHIRO Alzheimer’s disease, Neurology 1984;34:939– ficulty on inspiration was improved by Department of Neurology 44. tracheostomy. The respiratory flow volume 7 Heilman KM, Bowers D, Speedie L, et al. Com- loop study did not detect abnormality in N NISHIZAWA prehension of aVective and nonaVective Department of Oto-Rhino-Laryngology, Hokkaido speech. Neurology 1984;34:917–21. patient 2. University School of Medicine, Hokkaido, Japan 8 Tucker DM, Watson RT, Heilman KM. Dis- The CAG repeat number tended to be crimination and evocation of aVectively in- higher in the patients with VCAP than in the K TAKAMOTO toned speech in patients with right parietal dis- Department of Neurology, Tokyo Metropolitan ease. Neurology 1977;27:947–50. patients without VCAP (p=0.05), but the duration of illness was not significantly Neurological Hospital, Tokyo, Japan correlated with the presence of VCAP T YOKOTA Vocal cord abductor paralysis in (p=0.43). H MIZUSAWA spinocerebellar ataxia type 1 This is the first report that VCAP is often Department of Neurology, found in patients with SCA1. As VCAP may Tokyo Medical and Dental University, Tokyo, Japan Vocal cord abductor paralysis (VCAP) is not usually be a late feature in patients with Correspondence to: Dr Toshiaki Shiojiri, Depart- considered a sign of a poor prognosis in neu- SCA1, evaluation of VCAP is necessary even ment of Neurology, Asahi General Hospital, I-1345, rodegenerative diseases, because severe la- in early stages of the disease. It is not surpris- Asahi-city, Chiba 289–2511, Japan. Telephone 0081 479 63 8111; fax 0081 479 60 1210. ryngeal dysfunction by VCAP may result in ing to find VCAP in patients with stridor, acute airway obstruction and require emer- because stridor is usually caused by airway 1 gency tracheotomy. obstruction of the larynx. However, VCAP 1 Williams A, Hanson D, Calne DB. Vocal cord Although VCAP is a cardinal feature in was detected by laryngofibroscopy in a paralysis in the Shy-Drager syndrome. J Neurol multiple system atrophy (MSA), it has not patient without stridor who had dysphagia. Neurosurg Psychiatry 1979;42:151–3. been reported in several types of spinocer- Furthermore, all patients with VCAP exhib- 2 Isozaki E, Shimizu T, Takamoto K, et al. Vocal cord abductor paralysis (VCAP) in Parkinson’s ebellar ataxia with dominant inheritance. We ited dysphagia. We therefore think that laryn- disease: diVerence from VCAP in multiple sys- evaluated the movements of the vocal cords gofibroscopy should be performed in SCA1 tem atrophy. J Neurol Sci 1995;130:197–202. of seven patients with SCA1 by laryngofibro- patients with dysphagia as well as stridor. 3 Hayashi M, Isozaki M, Oda M, et al. Loss of scopy. The mechanism of VCAP may be divided large myelinated nerve fibers of the recurrent laryngeal nerve in patients with multiple Seven unrelated patients with SCA1 who into some types, the paralytic type, the non- system atrophy and vocal cord palsy. J Neurol had the expanded CAG repeat of ataxin-1 paralytic type, and these two combined type.2 Neurosurg Psychiatry 1997;62:234–8. were investigated. There were two men and The first is possibly caused by loss of 4 Isozaki E, Naito A, Horiguchi S, et al. Early five women ranging in age from 27 to 67 years neurons in the nucleus ambiguus.23 The diagnosis and stage classification of vocal cord abductor paralysis in patients with multiple old (mean 44.5 years). Spouses and other second is considered to be due to over- system atrophy. J Neurol Neurosurg Psychiatry family members, in addition to the patients, activity of the intrinsic laryngeal muscles.2 1996;60:399–402. were questioned about events of stridor, dys- Stridor due to paralysis has been found to be 5 Genis D, Matilla T, Volpini V, et al. Clinical, pnoea, and dysphagia. Vocal cord movement more prominent in sleep than during wake- neuropathologic and genetic studies of a large spinocerebellar ataxia type 1 (SCA1) kindred: was examined by laryngofibroscopy and fulness; whereas stridor by non-paralytic (CAG)n expansion and early premonitory recorded during inspiration and phonation. dysfunction has been found both during the signs and symptoms. Neurology 1995;45:24–30.

Brief summary of the clinical features and CAG repeat numbers in the patients with SCA1

Disease Vocal cord Stridor at Stridor during Breathing (CAG)n of Patient Age/sex Onset (y) duration (y) paralysis* night wakefulness Dysphagia diYculty Tracheotomy mutant allele 1 30/M 28 2 + − − + − − 53 2 48/F 39 9 + + − + − − 48 3 27/F 20 7 ++ + − + + − 59 4 34/M 23 11 ++ + − + + + 52 5 56/F 46 9 +++ + + + + + 47 6 67/F 51 14 − + − + − − 46 7 50/F 41 8 − − − − − − 46

*(−)=normal, (+)=median position, (++)=paramidline position, (+++)=midline position. 696 Letters, Correspondence, Book reviews, Correction

Lateral gaze synkinesis on downward showed saccade oscillations (usually square a bilateral thalamomesencephalic infarct saccade attempts with paramedian and macrosquare wave jerks)—that is, back which involved predominantly the right thalamic and midbrain infarct to back involuntary horizontal saccades with side. an amplitude ranging from about 2 to about Horizontal gaze deviation on attempted downward saccades disappeared after about The symptoms of paramedian thalamic and 10 degrees and with an intersaccadic interval 15 days, whereas vertical gaze impairment midbrain infarct include ocular motor distur- of about 200 ms, that brought the eyes away bances mainly in the vertical plane.1 We here from and back to the fixation point, at an and hypersomnia were unchanged 1 year describe a patient with the additional feature approximate rate of three every 2 seconds. later. Subsequent polisomnographic testing of an unusual horizontal eye movement Clinical examination of eye movements in disclosed sleep apnoea. synkinesis. the horizontal plane and visually guided The clinical features of our patient A 60 year old overweight man, reflexive saccades recorded by the infrared are those reported for thalamic infarct with diabetes and mild hypertension, reflection technique were both normal, involving the rostrointerstitial nucleus of suddenly fell into a coma that lasted whereas the amplitude range of vertical sac- the medial longitudinal fasciculus (riMLF). for 4 hours and was followed by slight right cade and smooth pursuit eye movements By contrast, the leftward gaze deviation elic- ited by the attempt to make a downward sac- hemiparesis, recent memory impairment, covered only a few degrees of upward gaze. cade is at variance with all previous descrip- hypersomnia, and vertical gaze impair- Vertical amplitude range was slightly greater tions. ment. for the vestibulo-ocular reflex in the pitch The triggering of a saccade requires not On admission to our centre, about 10 days (yes-yes) plane. Moreover, when the patient only the activation of the exitatory burst neu- after symptom onset, the patient still pre- attempted to make a downward saccade, he sented fluctuating drowsiness from which he rons (EBNs), but also the deactivation of the showed a gaze deviation to the left (figure). could be easily aroused, normal cognitive omnipause neurons (OPNs), which provide This synkinesis was more evident when the functions with mild attention disturbance, tonic inhibition of both horizontal and verti- slight right facial weakness, and mild incoor- examiner lifted the patient’s lids, thus cal EBNs. dination at the finger-to-nose test with his preventing lid synkinesis during downgaze. Accordingly, any attempt to activate a right arm. Attempted upward saccades did not lesioned riMLF should be associated with The most important findings involved produce any horizontal gaze deviation. maximal OPN inhibition. However, OPNs ocular motor function. Both pupils were Finally, the patient showed normal Bell’s discharge for saccade in any direction and are normal in diameter and reacted normally phenomenon. not strictly direction selective,2 as shown by both to light and to convergence. The cover An EEG showed frontal, bilateral horizontal oscillations during vertical sac- test did not disclose any eye misalignment. theta and theta/delta activity and sporadic cades detectable in normal subjects.3 These During attempted fixation, the patient drowsiness, and MRI (figure) disclosed oscillations suggest that during vertical sac- cades the inhibition of OPNs disinhibits both vertical and, to a lesser extent, horizontal EBNs. In our patient, the horizontal gaze devia- tion was always directed to the left rather than in both directions as during oscillations. Many ocular motor structures, including those located in the midbrain,4 trigger a purely vertical (downward) saccade only when stimulated bilaterally, so as to nullify horizontal components with diVerent direc- tion depending on the stimulation side. This probably occurs for the riMLF too, as it shows ipsilateral projections to the abducens nucleus.5 In our patient, the projections to the left nucleus were probably spared by the fact that the lesion predominantly aVected the right side. Overall, our patient’s horizontal ocular motor synkinesis is unusual, and probably derives from a strong inhibition of OPNs, C which in turn frees the horizontal EBNs, and from an unbalanced activation of the left abducens neurons via riMLF projections spared from the lesion, although it is not pos- R 0 deg sible to exclude the possibility that the unbal- anced activation of abducens neurons origi- 8 deg nated from frontal or parietal cortical areas or L from the superior colliculus rather than from riMLF projections. left eye horizontal This hypothesis is strengthened by the reinforcement of the leftward eye deviation when the examiner kept the patient’s lids lifted. Since this manoeuvre right eye vertical prevents lid synkinesis, it results in what resembles an attempted forced lid closure which, on the basis of blink induced eye 6 0.5 s oscillations, is likely to be an additional stimulus for OPN inhibition. Moreover, although they occur in various conditions, (A) and (B) show a thalamomesencephalic ischaemic lesion, hyperintense in T2 weighted saccade oscillations during fixation are in scans (SE, TR=2300 ms; TE=25 ms). The lesion involves the anteromedial portion of both thalami, keeping with a reduction of OPN inhibition but the right one to a larger exrtent. In the midbrain, the lesion is located around the Sylvian level.7 acqueduct, and symmetrically, but prevalently right sided, and involves the area that is located In conclusion, our patient presented an posteromedially with respect to both red nuclei. (C) Recording of the horizontal (upper tracing) and ocular motor synkinesis that should be listed of the vertical (bottom tracing) movement recorded respectively from the left and right eye with the infrared reflection technique (Skalar, IRIS system) during an attempted downward saccade. The among those occurring in thalamomesen- vertical tracing is flat, as the patient was unable to move his eyes downward. By contrast, the cephalic infarcts. This sign is unusual and it horizontal tracing shows a concomitant leftward saccade. At outset, both tracings show a blink is likely to be overlooked, but it is fully artifact. explicable both by neurophysiology and Letters, Correspondence, Book reviews, Correction 697 by anatomical connections of the saccade blocking SNAP-25, a protein involved in the system. fusion of acetylcholine containing vesicles Systemic sclerosis (scleroderma) is a multi- 5 system connective tissue disease of unknown M VERSINO with the plasma membrane. F SIMONETTI Against this background we evaluated the aetiology, characterised by progressive fibro- MGEGITTO usefulness of botulinum toxin injections into sis of the skin and internal organs including M CERONI the parotid gland in four patients with exces- the lungs and gastrointestinal tract.1 Patho- V COSI sive drooling of saliva, with their consent. logical calcification of soft tissues (known as Fondazione IRCCS Istituto Neurologico C Mondino, One patient had young onset secondary gen- calcinosis) is a common feature in the Pavia, Italy eralised dystonia with severe mouth opening CREST syndrome of scleroderma (calcino- M VERSINO spasms, one had advanced Parkinson´s dis- sis, Raynaud’s phenomenon, oesophageal M CERONI ease, the third patient had progressive supra- dysmotility, sclerodactyly, telangiectasia). By V COSI nuclear palsy, and the fourth patient had contrast, internal organ calcification is rare, Dipartimento Scienze Neurologiche motor neuron disease. Drooling in these and isolated cases of spinal calcinosis and G BELTRAMI patients was so severe that they had to wear a calcific constrictive pericarditis have been Dipartimento di Informatica e Sistemistica, bib or carry a towel around their neck. With reported.23 We report here the cases of two Università di Pavia, Italy one exception 20 units of Dysport( (Ipsen) patients with systemic sclerosis whose CT Correspondence to: Dr Maurizio Versino, Diparti- were injected superficially subcutaneously examination disclosed extensive brain calcifi- mento Scienze Neurologiche, Università di Pavia, above the angle of the mandible at the poste- cations. Fondazione Istituto Neurologico C Mondino rior margin of the masseter muscle, avoiding Case 1, a 48 year old man was referred to IRCCS, Via Palestro 3, 27100 Pavia, Italy. Tele- the bulk of the muscle. The shorter version hospital because of polyarthralgia involving phone 0039 0382 380340; fax 0039 0382 380286; (5/8”) of the 25 gauge needle was used. email [email protected] the wrists and ankles, Raynaud’s phenom- Because worsening of dysphagia was feared enon, and tightness of hand skin. The only 10 U Dysport were injected into each patient’s wife had noticed that during the 1 Castaigne P, Lhermitte F, Buge A, et al. parotid gland in the patient with motor neu- previous months, he had a slowed mentation Paramedian thalamic and midbrain infarcts: ron disease. Drooling did not significantly and a depressive mood. Physical examination clinical and neuropathological study. Ann Neu- improve in this patient, possibly due to the disclosed a sclerodactyly but no telangiecta- rol 1981;10:127–48. low dose of botulinum toxin used. He 2 Nakao S, Shiraishi Y, Li W, et al. Cat pontine sias. Routine haematological tests were nor- omnipause neurons: direct inhibitory connec- declined further treatment. mal. Antinuclear antibodies were positive at a tion with Forel’ s field burst neurons participat- All the other patients had a beneficial 1/2000 dilution with nucleolar fluorescence. ing in the genesis of vertical saccades. Acta response beginning by the end of the first Otolaryngol 1991;481(suppl):199–204. Rheumatoid factors, antidouble stranded 3 Zee DS, Fitzgibbon EJ, Optican LM. Saccade- week and lasting 6 weeks in one patient and 3 DNA and antiphospholipid antibodies were vergence interactions in humans. J Neurophysiol to 4 months in the others. Apart from subjec- negative. There was no cryoglobulinaemia. 1992;68:1624–41. tive improvement reported by the patients Complement was normal. Lung function 4 Kömpf D, Pasik T, Pasik P, et al. Downward and caregivers, reduction of drooling was gaze in monkeys. Stimulation and lesion tests showed a restrictive syndrome (forced studies. Brain 1979;102:527–58. demonstrated by the fact that the patients did vital capacity=75% predicted). Chest radio- 5 Langer T, Kaneko CRS, Scudder CA, et al. not have to use a bib or towel. One patient graphy was normal, as were oesophageal AVerents to the abducens nucleus in the mon- had mild worsening of existing dysphagia. manometry and cardiac ultrasonographic key and cat. J Comp Neurol 1986;245:379–400. Two patients had mild chewing diYculties, 6 Hain TC, Zee DS, Mordes M. Blink-induced examination. A diagnosis of systemic sclerosis saccadic oscillations. Ann Neurol 1986;19:299– possibly due to diVusion of the toxin into the was made and the patient was given diltiazem 301 masseter and one patient complained of a dry (180 mg/day) and ketoprofene (150 mg/day). 7 Averbuch-Heller L, Kori AA, Rottach KG, et al. mouth. None developed facial weakness. All Dysfunction of pontine omnipause neurons Six months later the patient’s neurological causes impaired fixation: macrosaccadic oscil- three patients considered the response good status had worsened. He complained of lations with unilateral pontine lesion. Neu- enough and side eVects suYciently minimal memory loss, poor concentration, and insom- roophthalmology 1996;16:99–206. for them to continue botulinum toxin treat- nia. On neurological examination he was ment at regular intervals. anxious and very slow in answering ques- Injections of botulinum toxin into the tions. Mini mental state examination score Botulinum toxin is a useful treatment in parotid gland (and other salivary glands) may excessive drooling of saliva was 22/30. The patient was oriented to place, be an eVective and simple treatment for but not to time. Anterograde amnesia was excessive disabling drooling of saliva in noted. Agnosia, apraxia, and aphasia were Excessive drooling of saliva or hypersialor- selected patients. rhea is a common problem in neurodegenera- absent. There was no muscle weakness and tive disorders such as motor neuron disease muscle tone was normal, as were tendon AM was supported by the Ernst Jung-Stiftung für reflexes. Plantar responses were both flexor. or Parkinson´s disease. It is usually caused by Wissenschaft und Forschung in Hamburg, Ger- swallowing dysfunction and can facilitate many. There was no sensory loss or impairment of cranial nerves. Systemic sclerosis signs were choking, aspiration, and chest infections. KP BHATIA Socially it is embarrassing and disabling. A MÜNCHAU unchanged. Routine hematological tests were There are not many treatment options. Anti- P BROWN normal. Results of blood chemical tests were cholinergic drugs are sometimes tried but are Institute of Neurology, Queen Square, also unremarkable (serum electrolytes, urea, usually of little benefit and side eVects London, UK creatinine, iron), including phosphorus and (orthostatic hypotension, dizziness, and men- Correspondence to: Dr Kailash P Bhatia, Univer- calcium metabolism (serum parathyroid hor- tal confusion, particularly in the elderly) limit sity Department of Clinical Neurology, Institute of mone concentration, blood calcium and their usefulness. Neurology, Queen Square, London WC1N 3BG, phosphorus, 25-hydroxyvitamin D, 1,25- Occasionally, as a more drastic treatment UK. Tel 0044 171 837 3611 extention 4228; fax dihydroxyvitamin D, calciuria, and phospha- irradiation of the parotid gland is carried out 0044 171 278 5616; email HYPERLINK turia). Serum concentrations of free trio- when hypersialorrhea becomes intractable. mailto:[email protected] dothyroxine, free thyroxine, and thyroid Apart from its established usefulness in stimulating hormone were normal. Serologi- 1 Naumann M, Zellner M, Toyka KV, et al. Treat- cal tests for syphilis, HIV-1,2, and Lyme dis- dystonia, spasticity and strabismus there are ment of gustatory sweating with botulinum some data showing that botulinum toxin toxin. Ann Neurol 1997;42:973–5. ease were negative. Brain CT showed bilat- injections are eVective in autonomic 2 Schnider P, Binder M, AuV E, et al. Double- eral extensive calcification in the dentate disorders—for example, gustatory sweating1 blind trial of botulinum A toxin for the nuclei (figure 1A), basal ganglia, and subcor- 2 treatment of focal hyperhidrosis of the palms. and hyperhidrosis of the palm. It has been Br J Dermatol 1997;136:548–52. tical white matter (figure 1B). On MRI T1 hypothesised that botulinum toxin may help 3 Bushara KO. Sialorrhea in amyotrophic lateral weighted images and T2 weighted images, in sialorrhea.3 In a historical note Erbguth sclerosis: a hypothesis of a new treatment: calcification was visible as a low intensity sig- recently pointed out the potential use of botulinum toxin A injections of the parotid nal. The patient was given fluoxetine (20 glands. Med Hypothesis 1997;48:337–9. botulinum toxin for hypersalivation, quoting 4 Erbguth FJ. Botulinum toxin, a historical note. mg/day) and bromazepam (6 mg/day). At fol- a paper by the German physician and poet Lancet 1998;351:1820. low up, 1 year later, the patient’s clinical sta- Justinus Kerner written in 1817.4 5 Blasi J, Chapman ER, Link E, et al. Botulinum tus was unchanged, as was brain CT. toxin selectively cleaves the synaptic protein Botulinum toxin inhibits acetylcholine re- SNAP-25. Nature 1993;365:160–3. Case 2, a 64 year old right handed woman lease in nerve terminals mainly at the neuro- was admitted to hospital for evaluation of a muscular junction, but also in sympathetic Raynaud’s phenomenon which had lasted for and parasympathetic ganglion cells and in Extensive brain calcifications in more than 10 years. At physical examination, postganglionic parasympathetic nerves, by systemic sclerosis: two cases sclerodactyly and tightness of the facial skin 698 Letters, Correspondence, Book reviews, Correction

CREST syndrome. Arthritis Rheum 1996;39: 347–50. 4 Harrington MG, Macpherson P, McIntosh WB, et al. The significance of the incidental finding of basal ganglia calcification on computed tomography. J Neurol Neurosurg Psychiatry 1981;44:1168–70. 5 Ellie E, Julien J, Ferrer X, et al. Extensive cerebral calcification and retinal changes in pseudohypoparathyroidism. J Neurol 1989;236: 432–4. 6 Heron E, Fornes P, Rance A, et al. Brain involvement in scleroderma: two autopsy cases. Stroke 1998;29:719–21. 7 Anderson HC. Calcific lesions: a concept. Arch Pathol Lab Med 1983;107:341–8.

CORRESPONDENCE

Brain CT of case 1 shows dense symmetric calcifications in the dentate nuclei (1A) and basal ganglia (1B). All tibial foot: an electrophysiological were noted. Telangiectasias were present on in more than 30 conditions, including abnor- artifact the face, hands, and palate. The patient com- malities of calcium phosphorus metabolism 5 plained of pyrosis. Oesophageal manometry such as pseudohypoparathyroidism. Yamashita et al1 claim they have proved an showed abnormalities of oesophageal motil- Systemic sclerosis leads to the formation of “all tibial foot” for the motor innervation, an ity. Hand radiography disclosed soft tissue calcium deposits in the subcutaneous tissue. anomalous dual innervation of the tibialis calcifications. Anticentromere antibodies Rarely, the calcific process has been shown to anterior muscle by the deep peroneal and were positive at a 1/1000 dilution. A CREST involve the spine or pericardium.23Recently, posterior tibial nerve, and a sensory coinner- syndrome was diagnosed and the patient was Heron et al described two cases of cerebral vation of the skin between the first and given buflomedil (600 mg/day) and pred- involvement in systemic sclerosis.6 In both second toes by the tibial and deep peroneal nisone (25 mg/day). cases necropsy showed extensive wall calcifi- One year later she was admitted for the cation of the small arteries and arterioles of nerve in a patient. To support their view they quote the letters of Linden and Berlit2 and of evaluation of recent transient ischaemic the brain. Our two patients have scleroderma 3 4 attacks (TIAs). During the previous week she and extensive striopallidodentate calcifica- Glocker et al, ignoring our letter and that of 5 had experienced three bouts of expressive tions and metabolic investigations failed to Magistris and TruVert , both considering the aphasia and right hemiplegia, each lasting disclose any specific aetiology in either case. conclusions of Linden and Berlit and Glocker about 10 minutes. She never smoked and did We think that scleroderma should be added et al to be wrong. I point out that the not have diabetes, hypertension, or dyslipi- to the list of conditions described as occur- mentioned letter of Linden and Berlit2 and daemia. The neurological examination was ring with basal ganglia calcification. our response to it were published in the same normal. Routine blood chemical tests were The pathogenesis of the formation of issue. normal (serum electrolytes, urea, creatinine) calcium deposits in systemic diseases remains We have recorded a compound muscle including phosphorus and calcium metabo- poorly understood. However, pathological action potential (CMAP) with a negative ini- lism (serum parathyroid hormone concentra- calcification can be subdivided into meta- tial deflection on tibial nerve stimulation in tion, blood calcium and phosphorus, 25- static (occurring in undamaged tissues when 83% of 50 subjects, using a surface electrode hydroxyvitamin D, 1,25-dihydroxyvitamin D, extracellular calcium and phosphate concen- over the extensor digitorum brevis.4 In the calciuria, and phosphaturia). Cranial CT trations are increased) and dystrophic (ocur- same subjects no potential was recorded by showed bilateral calcifications of the basal ring in injured tissue when extracellular means of a concentric needle electrode ganglia, and faint calcifications of the dentate calcium and phosphate concentrations are inserted in the extensor digitorum brevis.1 In nuclei and rubrum nucleus. Moderate cer- normal) calcification.7 In our patients, as in our view, this proves that the CMAP recorded ebral and cerebellar atrophy was noted. the patients of Heron et al, the brain calcifying by surface electrode over the extensor digito- Duplex carotid ultrasound and 24 hour ECG process may be related to primary cerebrov- rum brevis on tibial nerve stimulation is a recording were normal. Echocardiography ascular changes induced by systemic sclero- remote potential originated in the plantar showed a normal left ventricle with an sis. muscles (volume conducted potential). Fur- ejection fraction of 60%. There was mild cal- Routine brain CT examination in systemic thermore, we consider that the CMAP cification and a thickening of the mitral valve sclerosis could help to determine the true recorded over the tibialis anterior muscle by leaflets. Aspirin (250 mg daily) was given at incidence of basal ganglia calcifications and surface electrode on tibial nerve stimulation hospital discharge. No further TIA occurred their clinical relevance. in the popliteal fossa, as reported by Yamas- duringa5yearfollow up and the patient’s 1 PATRICK BLANCO hita et al, represents a volume conduction clinical status has remained unchanged. JEAN-FRANÇOIS VIALLARD potential originating in the foot and toe flex- Systemic sclerosis is a multisystem disease EMMANUEL ELLIE ors. The sensory nerve action potential predominantly aVecting the skin, lungs, ISABELLE FAURE recorded dorsally in the space between the vascular system, and gastrointestinal tract.1 PATRICK MERCIÉ Neurological involvement occurs in a few JEAN-LUC PELLEGRIN first and the second toes on tibial nerve patients (ranging from 0.8 to 18.5%) includ- BERNARD LENG stimulation could also be a volume con- ing cranial nerve abnormalities, peripheral Clinique de Médecine Interne, Hôpital Haut-Lévêque, ducted potential originating in the first com- neuropathy, CNS vasculitis, and autonomic avenue de Magellan, 33604 Pessac, France mon plantar digital nerve, as the distance peripheral neuropathy. To our knowledge, Correspondence to: Dr Jean-François Viallard, between this nerve and the recording elec- extensive cerebral calcifications have not yet Clinique de Médecine Interne, Hôpital Haut- trode is short. Such volume conduction phe- Lévêque, Centre François Magendie, 33604 Pessac, been reported. nomena are known to occur on surface France. Telephone 0033 556556483; fax 0033 recordings from the median nerve at the wrist Calcification of the brain is discovered in 556556484. 0.8 to 1.2% of subjects undergoing routine in severe carpal tunnel syndrome, when the CT examination, mainly in the globus forth finger is stimulated. It is unclear why pallidus. In most cases the deposits are small 1 Seibold JR. Scleroderma. In: Kelley WN, Harris Yamashita et al could not record a CMAP ED, Ruddy S, et al,eds.Textbook of Rheumatol- over the extensor digitorum brevis bilaterally and involve older patients who remain ogy. Philadelphia: WB Saunders 1997:1133– asymptomatic, leading to the concept of 62. on deep peroneal nerve stimulation in their “physiological” senescent basal ganglia 2 Ward M, Curé J, Schabel S, et al. Symptomatic young patient who did not have neuropathy. calcifications.4 On the other hand, basal gan- spinal calcinosis in systemic sclerosis (sclero- A probable explanation is a bilateral aplasia of derma). Arthritis Rheum 1997;40:1892–5. glia calcifications, often associated with den- 3 Panchal P, Adams E, Hsieh A. Calcific constric- the extensor digitorum brevis, comparable tate nuclei calcifications, have been reported tive pericarditis. A rare complication of with the known aplasia of the thenar.6 The Letters, Correspondence, Book reviews, Correction 699 appropriate examination would have been a planning and execution of any clinical Chronic Fatigue and its Syndromes.By needle EMG of the extensor digitorum research. For clinicians, psychologists, occu- SIMON WESSELY, MATTHEW HOTOPF, and brevis. pational therapists, and other members of the MICHAEL SHARPE. (Pp 428, £29.50). GEORGIOS AMOIRIDIS multidisciplinary old age psychiatry team, the Published by Oxford University Press, Department of Neurology, University of Crete, PO Box collection of so many scales covering all Oxford, 1998. ISBN 0-19-263046-6. 1393, 71 110 Heraklion, Crete, Greece. Telephone aspects of mental health of elderly people 0030 81 394651; email [email protected] should encourage the use of valid and reliable My first sensation is that such a book is long assessment procedures that enhance rather overdue. There is a paucity of books written by 1 Yamashita M, Mezaki T, Yamamoto T. “All than detract from good clinical practice. My clinicians on this subject compared with the tibial foot” with sensory crossover innervation only question is “Why didn’t somebody do many gloom and doom tracts written by between the tibial and deep peroneal nerves. J this before”. suVerers who have apparently been ill with Neurol Neurosurg Psychiatry 1998;65:798–9. CFS/PVS/ME for 20 years and which depress 2 Linden D, Berlit P. The intrinsic foot muscles SIMON LOVESTONE are purely innervated by the tibial nerve (all the hell out of the patients that I see. Why this tibial foot): an unusual innervation anomaly. lack? Undoubtedly because relatively few doc- Muscle Nerve 1994;5:560–1. 3 Glocker FX, Deuschl G, Lucking CH. Trau- Lumbar Disc Herniation.ByFRANCO tors want to put their heads above the parapet matic lesion of the common peroneal nerve POSTACCHINI. (Pp 623, US$299.00). and profess to a great expertise or desire to see with complete foot drop and preserved dorsi- Published by Springer-Verlag, Wien, 1999. patients with it. It is a condition for which there flexion of the toes: an innervation anomaly. is no objective test, no objective monitoring of Muscle Nerve 1995;8:926–7. ISBN 3-211-83118-5. 4 Amoiridis G, Schols L, Meves S, et al. Fact and progress, whose symptoms are so vague that fallacy in clinical and electrophysiological they repeatedly defy classification and can only studies of anomalous innervation of the intrin- Professor Franco Postacchini is an orthopae- be catalogued. Among those patients with a sic foot muscles. Muscle Nerve 1996;9:1227–9. dic surgeon at the University “La Sapienza” in 5 Magistris MR, TruVert A. Extensor digitorum genuine postinfectious fatigue (who mainly get brevis innervated by the tibial nerve (all tibial Rome and is a well known widely respected better relatively quickly) there is a large body of foot): anomalous innervation or technical spinal surgeon. He is to be congratulated on those with hospital records measured by the pitfall? Muscle Nerve 1997;7:906–8. the production of this book which is wide kilogram who arrive with sheaves of self com- 6 Iyer KM, Stanley JK. Congenital absence of ranging, comprehensive, and beautifully illus- flexor pollicis brevis and abductor pollicis piled additional notes and occupy huge brevis. Hand 1982;3:313–6. trated. The management of lumbar disc periods in the clinic to little eVect other than disease is fraught with uncertainty and there frustration for both doctor and patient. Why are many diagnostic and therapeutic pitfalls. they do this is a diVerent story. The author has succeeded in addressing most So what about the book? Firstly I must say of these controversies in a clear and logical it comes armour plated against criticism with BOOK REVIEWS fashion. He occasionally blurs the distinction a pack of glowing references from ennobled between theories and established scientific fact and famous physicians on the back. Presum- forgetting that the practice of medicine and in ably the authors chose these referees whose particular the management of spinal disorders major feature in common is distinction in is full of paradoxes. For example, he states that fields other than chronic fatigue syndrome. Assessment Scales in Old Age large extruded disc fragments are unlikely to So, for whatever reason they were chosen the .byALISTAIR BURNS, BRIAN Psychiatry resolve spontaneously and will usually require result is also to make this a poisoned chalice LAWLOR, and SARAH CRAIG. (Pp 302, £29.95). surgical treatment. This seems a logical to review if one has the temerity to disagree Published by Martin Dunitz, London, 1999. proposition but my experience is that many of with such a company. IBSN 1-85317-562-5. these large extrusions undergo complete clini- Chronic fatigue and its Syndromes is written by cal and radiological resolution within 2 or 3 three psychiatrists. That in itself is a little odd If it moves - measure it. Such is the trend in months. Paradoxically, it is often the smaller as although psychiatric illness is quite common psychiatry and this has led to a proliferation contained disc prolapses which fail to improve in the chronic fatigue syndrome group, most of assessment scales of variable utility; from with conservative measures. Like many ortho- patients with chronic fatigue syndrome are the esoteric to the ubiquitous. This book has paedic surgeons he is persuaded by the alluring very reluctant to be seen on first presentation them all and is, quite genuinely, one of the theories of discogenic low back pain and wor- by psychiatrists. One usually has to reassure most useful volumes I have seen for a very them that one is not dismissing their symp- ships at the altar of segmental microinstability. long time. It covers everything from the toms as psychiatric if one does suggest such a However, I agree with much that he has AMTS through the MMSE to the KEW cog- referral. What proportion of patients I wonder written and diVerences of emphasis are nitive test. Each scale is presented in full go to psychiatrists as their first hospital together with a short commentary, critical inevitable in a field that is strong on dogma referral? I would guess very few. references and, usefully, an estimated time and short of established truths. The book is very comprehensive. As a source taken to perform the test together with an I would have no hesitation in recommend- of references on the subject of fatigue it is address to contact the original author. ing the text to trainees as the book is very encyclopaedic. It begins with a nice history of The scales presented are divided into those readable and makes a good introduction to the syndrome. Of a 428 page book only 44 covering depression, neuropsychiatric assess- the management of lumbar disc disease. pages cover assessment of the patient and a ments, activities of daily living, global assess- Nearly all aspects of diagnosis and treatment very telling paltry 14 are devoted to treatment. ments, visible assessments, delirium, care- are covered but I was disappointed with the What is all the rest? The answer is that the giver assessments and scales for memory chapter discussing results of surgery. There is authors have attempted to deal with every function. This organisation, together with a no mention of the use of objective validated fatigue associated subject including: aetiology useful and functional index, will make the disability and quality of life instruments in of chronic fatigue syndrome (summary - not task of selecting an appropriate scale much the assessment of outcome. For a text that known) and in a move which Sir Humphrey easier in the future. Some of these scales are aims to be comprehensive this constitutes a Appleby might have described as “courageous“ covered by patent law and my only quibble is serious omission. It is because practitioners they have ventured way outside their own areas that it would have been useful to know which have failed to use objective outcome meas- of expertise into subjects such as viruses and instruments can be reproduced and for what ures to establish the natural history of lumbar immunity. The result is a collection of compre- purpose without fear of being billed for the disc disease and the eVects of therapeutic hensively referenced and uncritically selected privilege. Maybe highlighting such infor- interventions that there remains so much facts from the literature, many of which are very mation would give unpatented authors a uncertainty about management. These un- useful, such as the collected data on enterovi- stimulus to visit their lawyer and therefore certainties cover (among others) physi- ruses and chronic fatigue syndrome but much increase this deplorable practice. otherapy, manipulation, timing of radiology, of which is of uncertain value—for example, This aside, I cannot recommend this book timing of surgery, whether spinal fusion is “divorced and separated women have higher highly enough. By contrast with books that ever indicated, and what treatments are clini- titres of EBV-VCA antibodies” quoted out of come highly recommended in diverse reviews cally and cost eVective. Despite these draw- context but not unrepresentatively. To glean but remain pristine on your library shelf, if backs, surgeons who manage lumbar disc interesting and important information from you are ever fortunate enough to get hold of disorders will want to have a copy of this this book requires a fair degree of skill in this volume from your institution library then book, either on their own or their departmen- distinguishing timber from forest. you will, I guarantee, find it well thumbed. tal library’s shelf. When in their own field of psychiatry there For academics, the book is a prayer answered is, unsurprisingly, a much more confident and will become an essential resource in the RODNEY LAING and informative air to the book. It is 700 Letters, Correspondence, Book reviews, Correction disappointing and somewhat introspective determining why drugs work, or don’t work, in Advances and Technical Standards In that they did not think that subjects such as migraine. The book is up to date, containing Neurosurgery. Volume 24. Editor In Chief neurobiology, microbiology, and immunol- many 1998 references. Another strong point of F COHADON. (Pp 57, US$159.00). Published ogy might justify equally expert contributors. the book it its comprehensiveness; though only by Springer-Verlag, Wien, 1998. ISBN Is it an easy read? There is no easy way to 184 pages long, it covers every major aspect of write on a subject such as this, bedevilled by the pathophysiology of migraine. There are 3-211-83064-2. lack of objective facts and the writers have chapters on innervation of cranial blood chosen a discursive, debating style which vessels, receptor physiology, neurotransmit- Advances and Technical Standards in Neurosur- when not tightly controlled can slip towards ters, 5-hydroxytrptamine receptor subtypes, gery is sponsored by the European Associ- verbosity. This, however, is not a standard cortical spreading, depression, neurogenic ation of Neurosurgical Societies. The inten- medical text book and it would be unfair to inflammation, arteriovenous shunts, cerebral tion is to publish reviews of topics in which make direct comparisons.. haemodynamics, and animal modelling. This recent advances have been made, and to Is this a useful book? As a source of is achieved at the expense of some pretty terse invite acknowledged experts to present in references, yes. As a guide to clinicians I am prose at times, which can make it diYcult for depth accounts of established knowledge in less convinced. The two commonest questions the non-expert to follow. It should be noted various fields of neurosurgery. patients ask are hardly mentioned: “How long that, the title notwithstanding, this book deals The advances under review in this volume does the illness last?” and “What are my almost exclusively with the pathophysiology of are the contribution of the septal region to chances of recovery” Cognitive behavioural migraine, and the reader who buys it to get memory, the in vivo metabolic investigation therapy is concisely and usefully summarised. some insight into the mechanisms of tension- of cerebral gliomas with PET, and the use of There is a single page on complementary type headaches, or other kinds of headache, is image guidance in neurosurgery. In the tech- treatment, which again is often an area of con- going to be disappointed. nical standards section, Professors Valavanis siderable interest to patients notwithstanding Who should read this book? Certainly the and Yasargil discuss the endovascular treat- the lack of controlled evidence for or against it. migraine research should. Though much of it ment of arteriovenous malformations, Dr On that note it is perhaps appropriate to will be familiar to those who have kept up with Guglielmi reports on the interventional neu- quote one very intelligent patient with the literature, it is nevertheless an attractive roradiological treatment of intracranial aneu- chronic fatigue syndrome I saw who became and handy compendium of current research rysms, and Dr Sussman and colleagues ill during his PhD. “I’ve done a lot of reading information. Moreover, the first chapter (by describe the management of benign intracra- and internet searching about the causes and Lars Edvinsson) and the last chapter (by Peter nial hypertension. possible cures of this, before I came to see Goadsby) are very pretty syntheses of the field. This book is aimed primarily at young neu- you” he said “It seems to me that most peo- What about clinicians? Some of it is heavy rosurgeons, but is an excellent source of refer- ple have an illness a bit like that which you going for people like me, who are not basic sci- ence for those who are already trained. The commonly see after glandular fever and entists. But I got through it all in about 6 fact that it is in its 24th volume is a testament nobody seems to think it odd that after glan- hours, and found I knew more about migraine to its success in achieving this objective. dular fever you can feel unwell for quite a coming out than I did going in—which makes long time” he continued “If most people get reading it a very worthwhile exercise. ROBERT MACFARLANE better from this” (and many do) and if you try JOHN EDMEADS all sorts of other treatments like homoeopa- thy, acupuncture, meditation then the one Hospitalist Neurology. Blue Books of you were doing when you got better will be Systemic Diseases, Part II. By MJ AMINOFF Practical Neurology. Edited by MARTIN A the one you think cured you”. He had of and CG GOETZ. (Handbook of Clinical SAMUELS. (Pp 748, £70.00). Published by course discovered the maxim of entertaining Neurology, series edited by PJ VINKEN and GW Butterworth Heinemann, Oxford, 1999. the patient while nature gets them better. One BRUYN. (Pp 486, US$224.00). Published by ISBN 0750697792. could do worse perhaps than keep patients Elsevier Science, Amsterdam, 1998. ISBN with chronic fatigue syndrome occupied, if 044481289X. It seems that there is a new specialty in North not necessarily always entertained for quite a American neurology, hospitalist neurology. while, by recommending this book for them There is something about the anachronistic The drive to promote managed health care to read. They might end up with a greater binding of the Handbook of Clinical Neurol- has apparently resulted in hospitals “filled to understanding of fatigue and they would cer- ogy series that is rather reassuring. Surely if overflowing with more acutely ill patients tainly realise how little really is known and classic phenomenological neurology is to be requiring a pace of evaluation unprecedented how the search for an instant cure (which found anywhere, it will be between these fake anywhere in the world”. Enter the hospitalist drives many of them) is currently futile. leather embossed covers. This volume, the sec- neurologist. Unencumbered by the demands ANDREW LEVER ond of three on the neurology of systemic of outpatient neurology, he or she stumbles diseases, does nor disappoint. Here, in 450 through the wards of the general hospital pages of close type and few illustrations, are “faced with a dizzying array of neurologic Migraine and Headache Pathophysio- covered the neurology of orthopaedic, endo- problems”. Most British neurologists have a logy. Edited by LARS EDVINSSON. (pp 184, crine, gastrointestinal, and metabolic disorders. ward referral practice and will not be £65.00). Published by Martin Dunitz Goetz and AminoV, the volume editors, have impressed by its elevation to the status of a Publishers, London, 1999. ISBN assembled an authoritative panel of authors specialty and still less by the agrammatical 1-85317-737-7. that equitably straddle the Atlantic. There are title Martin Samuels has chosen for it. Which detailed reviews of familiar territory such as is a shame, because this book deserves a wide New information about how and why mi- diabetes, orthopaedic trauma, thyroid diseases, readership. One in the Butterworth Hein- graine happens continues to break on us in a and porphyria. Cole’s historical survey of B12 mann series of Blue Books of Practical Neu- dizzying succession of waves coming from deficiency is particularly fine. In addition there rology, it is attractively produced and reason- various journals in diVerent disciplines. We are excellent chapters on more arcane topics— ably well illustrated. Its place on your need an accessible, understandable, and uni- for instance the neurology of pancreatic trans- bookshelf is earned by collating the neuro- tary vehicle to collect, organise, and present plantation and intestinal pseudo-obstruction. logical aspects of diverse medical specialties: this information. Journals, the Internet, and Perhaps the movement disorders associated to name a few, organ transplantation, ortho- the abstracting services have their place, but with coeliac disease could have been men- paedics, oncology, and urology. A quick for this purpose nothing beats the book. How tioned and a chapter on the neurology of glance here before a ward referral might well well does Lars Edvinsson’s Migraine and inflammatory bowel disorders is certainly be rewarding. However, the chapters on more Headache Pathophysiology meet this need? lacking. But these are trifling complaints conventional neurological topics, such as This book has several attractive features. against a text that, with its twin volumes, is sig- neuro-ophthalmology, stroke, and seizures Recognising that some of the world’s best sci- nificantly more comprehensive than any other are probably briefer than most neurologists ence is now being done in the laboratories of account of the neurology of systemic diseases. would require. So, for those made dizzy by industry, it has enlisted as authors several It is hard to imagine a practicing neurologist the delirious patient after bypass, the en- leading researchers from the major pharma- requiring (or easily aVording) a personal copy cephalopathic flapping on the transplant ceutical manufacturing companies, in addition of all three volumes, but the local medical ward, or the weak and wasted on intensive library should certainly buy them; both to “the usual suspects” from academe. Not care units, this is for you. And remember: you neurologists and general physicians will work only has this introduced some exciting writers are a hospitalist neurologist. to the “review book” audience, but it has pro- the better for having them close to hand. vided a particular insight into the science of ALASTAIR COLES ALASTAIR COLES Letters, Correspondence, Book reviews, Correction 701

Symptom Management in Multiple Sclerosis, 3rd Edition.ByRANDALL T SCHAPIRO. (Pp 176, US$19.95). Published by CORRECTION Demos Medical Publishing, New York, 1998. ISBN 1-888799-22-6. Goldenberg G, Schuri U, Grömminger O, During printing, the figure in this paper (p This is one of a new type of medical Arnold U. Basal forebrain amnesia: does the 164) was made darker than the original. The textbook written to meet the needs nucleus accumbens contribute to human correct version appears below. of an increasingly informed patient memory? J Neurol Neurosurg Psychiatry 1999; population. Aimed very much at those with 67:163-8. multiple sclerosis, their families, and care- workers, it is simple and clearly written with jargon and technical terms kept to a A minimum but without patronising. Chronic diseases, and especially multiple sclerosis, are not always well managed by the physi- cian. Too many of us think that there is no cure and feel helpless in a busy clinic faced with the patient with a long list of com- plaints. There are too few specialty multiple sclerosis clinics in which neurologists, pain specialists, uroneurologists, physiotherapists etc liase. Patients often feel left in the dark, unaware which of their symptoms can be attributed to their multiple sclerosis and whether it is “worth bothering a busy doctor”. Many can cite bad experiences in their past when they have been fobbed oV with well meaning reassurance but without practical help. Dysaesthesia, sexual problems, and urinary incontinence are only a few of the symptoms that can bring misery to the lives of patients and their fami- lies and which are poorly addressed by doc- tors. This book, in a language accessible to most (and with a glossary to explain some unavoidable jargon), explains multiple B sclerosis, its symptoms, and what might realistically be obtained in terms of symptom control. All aspects are covered and nothing considered too trivial; constipa- tion or cold feet might be extremely trying for an individual patient and each is consid- ered. The old idea that is doesn’t help a Cd patient to know too much about his disease (“it will only make him introspective and hypochondrial”) is outdated. Multiple scle- rosis can hit anyone and patients now want, CI and deserve, to be informed. While doctors find it challenging to be faced with a patient equipped with the latest information down GP loaded from the internet or well informed having read a book such as this, this is a Acb challenge to which we must be ready to rise. This textbook provides the information patients want and fills the gap left by busy DB doctors. It should be marketed appropriately and we must be ready to respond to the reaction of patients. Perhaps someone with multiple sclerosis should have been invited to (A) T1 weighted MRI of the lesion. (B)Anatomical scheme of the centre of the lesion, corresponding write this review. to the leftmost image of the bottom row of the MRI. The right side of the figures corresponds to the left side of the brain. GP=globus pallidus; Cd=caudate nucleus, Acb=nucleus accumbens; CI=capsula GILLIAN HALL interna; DB=diagonal band.