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LETTERS TO

THE EDITOR

The rostrocaudal gradient for

somatosensory perception in the human

postcentral gyrus

Anatomical organisation of the primate post-central gyrus has been described in terms of several diV erent cytoarchitectures.1 2 Powelland Mountcastle stated that the area 3 was atypical koniocortex with granular cells,whereas in areas 1 and 2 the morphologicalcharacteristics changed gradually to thehomotypical parietal association cortex in themonkey Macaca mulatta.1 Iwamura e t al reported the physiological correlateson the anatomical rostrocaudal axis inmonkeys.2 The ratio of skin neurons to totalneurons was the largest in area 3b anddecreased gradually toward the caudal part of the postcentral gyrus.2 Specific types of stimulation such as rubbing of the skin in

certain directions were eV

ective in activatingsome of the caudal part of the postcentralgyrus. The anatomical and physiological datain the primate lead to the reasonabe hypoth-esis that there is a rostrocaudal functionalgradient within the postcentral gyrus. Thisnotion may explain why a lesion in the post-central gyrus causes varied sensory distur-bance in various people.

A 49 year old right handed man suddenlydeveloped dysaesthesia in the right hand.This recovered gradually, but 1 month laterhe still had an impaired tactile recognition forobjects. His voluntary movements were skill-ful. Deep tendon reflex was slightly exagger-ated in his right arm. Babinski’s sign wasabsent. His language was normal. Brain MRIon the 35th day after the onset showed alaminar necrosis on the caudal edge of thelateral portion of the left postcentral gyrus(figure).

Somaesthetic assessment was done duringthe 21–28th days of the illness.

Elementary somatosensory functions wereassessed, including light touch (long fibrecotton), pain (pinprick), thermal sensation(cold and hot water), joint position sense(tested by the ability of the patient to identifyflexion or extension of fingers with closedeyes), and vibration sense (128-Hz tuningfork).

Intermediate somatosensory tasks werecarried out. For two point discrimination, theexaminer placed a pair of plastic needles of aslide caliper on the index finger pad of thepatient, who had his eyes closed, and askedhim to answer the number of touchedneedles, “one” or “two”. For tactile localisa-

tion the examiner touched a point on theright or left hand of the patient, who had hiseyes closed, with a brush, then asked him toindicate the point by touching the place withthe first finger of the counter hand. Forweight perception, the patients were asked toarrange the stimuli in a correct order of theweight with either the left or right hand. Thestimuli were six metal plates of equal size,

shape, and texture weighing 50, 60, 70, 80,90, and 100 g. For texture perception, weprepared six wooden plates of an identicalsize and shape, on which one of six diV erenttextures (sandpaper, felt, wood, wool, finegrain, synthetic rubber) were mounted. Thepatient palpated one texture by either handwith his eyes closed. Then he was asked toselect tactually a correct one among the sixtextures. For shape perception (threedimensional figures) the patient palpated oneof the five wooden objects (cylinder, cube,sphere, prism,and cone) with his eyes closed.Then he was asked to explain the shape ver-bally. For extinction, the examiner deliveredlight and brief tactile stimuli, using the tips of the index fingers, to the dorsal surface of left,right, or both hands of the patient.

For tactile object recognition, the 15objects that are used in the naming list of theWestern aphasia battery test were presentedto either hand. For naming of objects, thepatient was asked to name a single manipu-lated object. In matching of objects, thepatient first grasps a single object among aselection of five objects, and then he wasasked to select the correct object among thefive.

In elementary sensory function, the test for

light touch, pain, thermal sensation, jointposition sense, and vibration sensedemonstrated no abnormalities for bothhands. The results of intermediate sensorytests showed that in all tests, except for shapeperception, we could detect no disturbance inboth hands. He could not discriminate theshape with his right hand. The correctresponses were 5/5 with the left hand and 0/5with his right hand. The correct responses inthe tactile naming test were 2/15 for the righthand and 15/15 for the left hand. The correctresponses of the tactile-tactile matching testwas 4/15 with his right hand and 15/15 withhis left hand. So the abilities of tactile recog-nition and tactile-tactile matching were dis-turbed with the right hand.

According to Delay, disturbances of the

tactile process in the cortex are classified intoat least three types.3 Ahylognosia is adistubance in the ability to discriminatematerials. Amorphognosia is a disturbance inthe diV erentiation of forms. Tactile agnosia isthe inability to recognise the identity of objects in the absence of ahylognosia andamorphognosia. In Delay’s terms, our patientshowed amorphognosia but not tactile agno-sia. Iwamura and Tanaka suggested that thehand region of area 2 in the rhesus monkey isconcerned with the tactile perception of thediscrimination of certain object forms.4 Thelesion localised at the equivalent corticalregion. This region thus may be critical forthe tactile discrimination for shape.

Rich intrinsic corticocortical connectionsare demonstrated within the rhesus monkey’s

postcentral gyrus, starting from Brodmannarea 3b and projecting to areas 1 and 2. 5 Thiscorticocortical connection may be a mainroute of inputs to area 2. This suggests thatwithin the postcentral gyrus somatosensoryinformation is processed from primary sensereception to integrating and more associatingstages. The results from our patient are com-patible with the notion that in the caudal por-tion of the human postcentral gyrus the morecomplex process such as shape perception isprocessed.

K TAKEDADepartment of Rehabilitation, Tokyo Metropolitan

Institute for Neuroscience, Tokyo MetropolitanOrganisation for Medical Research, Tokyo,Japan

Brain MRI of the patient. Transaxial T1 weighted (above) and T2 weighted images (below) areshown. The T1 weighted image disclosed a high intensity lesion distributed laminarly in the caudal edge of the left postcentral gyrus (Brodmann 1–2). Arrows indicate the left central sulcus.

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K TAKEDAY SHOZAWA

M SONOOT SHIMIZU

Department of Neurology, School of Medicine TeikyoUniversity, Tokyo,Japan

T KAMINAGADepartment of Radiology, School of Medicine Teikyo

University, Tokyo,Japan

Correspondence to: Dr Katsuhiko Takeda, Depart-ment of Neurology, Japanese Red Cross Medical

Center, Hiroo 4–1–22, Tokyo, 1–22, Shibuya-ku150–8935, Japan

Correspondence to: Dr Katsuhiko [email protected]

1 Powell TPS, Mountcastle VB. The cytoarchitec-ture of the postcentral gyrus of the monkeyMacaca mulatta. Bulletins of the Johns HopkinsHospital 1959;105:108–31.

2 Iwamura Y, Tanaka M, Sakamoto M, et al . Ros-trocaudal gradients in the neuronal receptivefield complexity in the finger region of the alertmonkey’s postcentral gyrus. Exp Brain Res1993;92:360–8.

3 Delay JPL. Les astéréognosies: Pathologie dutoucher . Paris: Masson, 1935.

4 Iwamura Y, Tanaka M. Postcentral neurons inhand region of area 2: their possible role in theform discrimination of tactile objects. Brain Res1978;150:662–6.

5 Vogt BA, Pandya DN. Corticocortical connec-tions of somatic sensory cortex (area 3, 1, and2) in the rhesus monkey. J Comp Neurol 1978;177:179–92.

Isolated spastic paraparesis leading to

diagnosis of Friedreich’s ataxia

Friedreich’s ataxia is the most commonhereditary ataxia. This neurological disorderwas initially defined by the association of ataxia, cerebellar syndrome, and pyramidalsigns. Atypical forms are increasingly recog-nised. The gene was mapped to 9q13-q21.1in 1988 and identified in 1996. We report ona patient with a spastic paraparesis, of whichmolecular analysis confirmed the diagnosis of

Friedreich’s ataxia.A 39 year old woman without any pastcondition presented with diYculty in walk-ing since the age of 20. Neurologicalexamination showed a spastic paraparesis,with tetrapyramidal signs, including general-ised brisk reflexes, bilateral Babinski’s signs,and clonus at the knees and ankles. Spastic-ity only concerned the lower limbs andspared the arms. Spastic paraparesis resultedin impaired walking at the time of the exam-ination. No other neurological abnormalitieswere found; notably, proprioception andvibration sense, and cerebellar function werenormal. No sensory symptoms were noted.No skeletal deformities were found. Allhematological investigations (including lac-tate and pyruvate concentrations, choles-

terol, apolipoproteinemia, Vitamin E, verylong chain fat acid concentrations, arylsulfa-tase, and hexosaminidase activities) werenormal. Electromyography, sensory andmotor nerve conduction studies in the upperand lower limbs, including sural nerve actionpotentials (right sural nerve action potential7 µV, normal>6 µV; left sural nerve actionpotential 8 µV, normal>6 µV) were normal.Cardiological tests (electrocardiography,transthoracic echocardiography) werenormal. Cerebral and spinal resonanceMRI were normal. No familial conditionwas found, except the sister who presentedthe same symptoms. No mutations involvedin mitochondriopathies were found

(3243tRNAleu, 8344tRNALys, nt 8993).The molecular analysis of the gene codingfor Friedreich’s ataxia was performed bySouthern blotting from DNA extracted fromperipheral blood and showed two abnormalexpansions of 2.5 kb and 3.1 kb on the chro-mosome 9q13-q21.1 (Dr M Schmitt, CHRUde Strasbourg, France). These expansionscorrespond to 830 and 1030 repeats. Diag-nosis of Friedreich’ s ataxia identified by anisolated paraparesis was definitevely re-

tained.Friedreich’s ataxia, an autosomal recessivedisorder, is one of the most common heredi-tary ataxias. The frequency of the gene isclose to 1/90 in the general population andthe prevalence of the disease is estimated tobe 1/50 000.Diagnosis is classically based onthe association of recessive inheritance, onsetbefore the age of 25, progressive ataxia of thefour limbs, loss of deep tendon reflexes,pyramidal signs, cerebellar dysarthria, distalloss of position and vibration sense, andelectrophysiological evidence of axonalneuropathy.1 Association of pes cavus, scolio-sis, cardiomyopathy, hearing loss, diabetes,and retinal disease are inconstantly seen. Bycontrast, atypical clinical symptoms areincreasingly encountered—for example, late

onset, brisk reflexes, spasticity, and slow pro-gression of the disease,2 and idiopathicataxia.3 Friedreich’s ataxia is a geneticallyhomogeneous condition. The frataxin genewas mapped to 9q13-q21.1 in 1988,4 andidentified in 1996.5 The mutations are mostoften GAA expansions located in the firstintron.5–7 Normal alleles range from 6 to 36GAA repeats, whereas pathological allelesrange from 90 to 1300 repeats.Ninety six percent of patients are homozygous for GAAtrinucleotide repeat expansions in the firstintron of the frataxin gene. The remainingpatients are compound heterozygotes for aGAA expansion and point mutations (mis-sense, nonsense, and splice site mutations).5 7

Frataxin, the protein encoded by the gene, isa protein associated with the inner mito-

chondrial membrane.8 It is thought toregulate the flux of iron in or out themitochondria. Identification of the mutatedgene allowed the correlation of certainphenotypes with genotypes. Larger expan-sions of the GAA repeats are correlated withan earlier age of onset, a faster progression of the disease, and additional clinical manifes-tations such as cardiomyopathy, pes cavus,scoliosis, and extensor plantar responses.6

The length of the expansion explains 50% of the variability of age at onset only. Other fac-tors are certainly involved in the phenotypevariability. We note that the correlations wereestablished from expansions measured inlymphocytic DNA. We cannot exclude thepossibility of somatic mutations. Thus, thelength of expansion in aV ected tissues wouldbe diV erent from the length found inlymphocytes. Some punctual mutations(D122Y, G130V) are correlated with a mildphenotype.7 Previous reports have noted thatpatients with Friedreich’s ataxia couldpresent with spasticity, usually associatedwith other neurological signs.9 Our report of isolated paraparesis confirmed again that thephenotypic range of Friedreich’s ataxia ismuch broader than previously considered.3 6

In addition, the spastic paraparesis presentedby our patient could be related to the cases of mitochondriopathies presenting with spasticparaplegia. Similar clinical symptoms inthese two diseases can be an additional argu-

ment for the implication of frataxin in mito-chondrial function.

G CASTELNOVOB BIOLSI

A BARBAUDP LABAUGE

Department of Neurology. CHU de Montpellier-Nîmes.CHU Caremeau. Avenue du Pr Debré. 30029 Nîmes

Cédex. France

M SCHMITTService de diagnostic génétique (Pr JL Mandel).

CHRU de Strasbourg. Faculté de Médecine. 11 Rue

Humann.67086 Strasbourg. Cédex. France

Correspondence to: Dr P [email protected]

1 Harding AE. Friedreich’s ataxia: a clinical andgenetic study of 90 families with an analysis of early diagnosis criteria and intrafamilial clus-tering of clinical features. Brain 1981;104:589– 620.

2 Richter A, Morgan K, Poirier J, et al . Friedre-ich’s ataxia in Acadian families from easternCanada: clinical diversity with conserved hap-lotypes. Am J Med Genet 1996;64:594–601.

3 Schöls L, Amoiridis G, Przuntek H, et al . Fried-reich’s ataxia. Revision of the phenotypeaccording to molecular genetics. Brain 1997;120:2131–40.

4 Chamberlain S, Shaw J, Wallis J, et al . Mappingof mutation causing Friedreich’s ataxia tohuman chromosome 9. Nature 1988;334:248– 50.

5 Campuzano V, Montermini L, Molto MD, et al .Friedreich’s ataxia: autosomal recessive diseasecaused by an intronic GAA triplet repeatexpansion. Science 1996;271:1423–7.

6 Dürr A, Cossee M, Agid Y, et al . Clinical andgenetic abnormalities in patients with Friedre-ich’s ataxia. N Engl J Med 1996;335:1169–75.

7 Cossee M, Dürr A, Schmitt M, et al . Friedre-ich’s ataxia: point mutations and clinicalpresentation of compound heterozygotes. Ann

Neurol 1999;45:200–6.8 Campuzano V, Montermini L, Lutzy, et al .

Frataxin is reduced in Friedreich’s ataxiapatients and is associated with mitochondrialmembranes. Hum Mol Genet 1997;6:1771–80.

9 Gates PC, Paris D, Forrest SM, et al . Friedre-ich’s ataxia presenting as adult-onset spasticparaparesis. Neurogenetics 1998;1:297–9.

Marked increase of interleukin-6 in

injured human nerves and dorsal root

ganglia

Nerve injury, particularly of the brachialplexus, may result in lifelong disability andchronic pain, despite technically excellentreconstructive surgery. Studies of molecularchanges in injured nerves may identify newtreatments to enhance the success of nerverepair, such as with recombinant humanneurotrophic factors. Interleukin-6 (IL-6) is amember of the neuropoietic cytokine familythat includes ciliary neurotrophic factor(CNTF), leukaemia inhibitory factor (LIF),and oncostatin M. As there is increasing evi-dence of a neurotrophic role for IL-6 in ani-mal models of ner ve injur y andinflammation,1 2 we have studied, for the firsttime in humans, IL-6 protein in injured and

control peripheral nerve and dorsal root gan-glia, using specific immunoassay, immunocy-tochemistry, and western blotting. We reporta most remarkable increase of IL-6 concen-trations in acutely avulsed dorsal root gangliaand injured nerves.

Proximal and distal injured nerve segmentswere obtained from six adult patients withtraction brachial plexus injury, ranging from2 weeks to 10 weeks after trauma. Injureddorsal root ganglia were collected from sevenadult patients with brachial spinal rootavulsion injuries (central axotomy), rangingfrom 3 days to 15 months after trauma.Tissue removal was a necessary part of thesurgical repair procedure; in all cases

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informed consent was obtained for tissue col-lection, and the study had ethics committeeapproval. Control dorsal root ganglia wereobtained from four subjects and segments of normal nerve from five subjects at postmor-tem, with a mean delay of 36 hours afterdeath; all died from myocardial causes.Tissue extracts prepared as previouslydescribed3 4 were analysed for IL-6 using anenzyme immunoassay (Pelikine CompactTM,Eurogenetics, UK Ltd, Middlesex, UK) withrecombinant human IL-6 standard calibratedagainst the World Health Organisation(WHO) First International Standard 89/548.For immunohistochemistry, frozen sections(8 µm) were fixed in 4% paraformaldehyde inphosphate buV ered saline for 30 minutes.Sections were incubated with monoclonalantibodies to IL-6 (CLB.IL-6/7 20 µg/ml,diluted 1:400; gift from K Nordlind,Sweden,or ref No 1618–01, Genzyme, USA) andimmunoreactivity to IL-6 visualised using astandard immunoperoxidase method (ABC;Vector Labs, UK) with nickel enhancementas described elsewhere.3 4 Specific immunore-activity was extinguished by a concentrationof rhIL-6 (ImmunoKontact, Frankfurt, ref 111–40–136) in the range 0.01–0.1 µg/ml.For western blotting, tissue extracts were

separated by gel electrophoresis on 15%acrylamide gels and then electrophoreticallytransferred to nitrocellulose membranes (Hy-bond Super, Amersham) using a semidrytransblotter. Strips were blocked in a solutionof 5% non-fat milk in phosphate buV eredsaline (PBS) containing 0.05% Tween-20 for1 hour and then probed with CLB.IL-6/7(with or without IL-6 peptide, 20 µl) at a finaltitre of 1:1000, for 2 hours. The strips werethen incubated with anti-rabbit HRP (Sigma)at 1:10,000 dilution fora further 30 minuttes.Bands were then visualised on x ray film aftertreatment with ECL reagents (Amersham).

Concentrations of IL-6 were increased ininjured nerves (figure). The increase wasgreater in nerve segments distal to injury, butIL-6 concentrations in both proximal and

distal segments were both significantly in-creased compared with controls (p<0.01,Mann-Whitney test). Concentrations of IL-6were greatly raised in two avulsed dorsal rootganglia obtained 3 and 4 days after injury(354 pg/mg and 128 pg/mg). At longeroperative delays after injury, IL-6 concentra-tions in avulsed dorsal root ganglia ap-proached the range of values obtained forpostmortem controls (4.9 (SD 2.9) pg/mg foroperative delays from 1 week to 15 months,and 0.2 (SD 0.06) pg/mg for controls). West-ern blotting showed the presence of anexpected strong 29 kDa band in detergentextracts of injured nerve, which was abolishedin the presence of excess synthetic IL-6.Immunohistochemical studies with both anti-bodies demonstrated IL-6 staining within the

soma of avulsed dorsal root ganglion neuronsof all sizes, particularly of small size.Immunostaining of postmortem gangliaseemed similar in pattern, but was generallyweaker. Interleukin-6 immunoreactivity wasalso seen in nerve-like structures within thedorsal root ganglia and distal injured nervesegments.

The pattern of changes of IL-6 in injurednerves and dorsal root ganglia diV ers fromthat seen for other neurotrophic factors, suchas nerve growth factor (NGF) and glial-derived neurotrophic factor (GDNF).3 4

Concentrations of IL-6 were usually higher indistal nerve segments when compared withthose proximal to the site of injury: this seems

to result from IL-6 synthesis in Schwann cellsin Wallerian degeneration, as shown byimmunostaining, and previous animal modelstudies.2 Interleukin-6 and its receptor havebeen shown to be required for normal nerveregeneration in animal models, which may beenhanced with exogenous IL-6.1 The injurednerves presumably take up IL-6 synthesisedin the Schwann cells, and transport itproximally, which accounts for the higherIL-6 concentrations in proximal segments of injured nerves in comparison with controls.Anterogradely transported IL-6,if released inthe spinal cord, may play a part in painprocessing, for which there is some evidencefrom animal models. In this study, the mostremarkable finding was the very high concen-tration of IL-6 in extracts of the acutelyavulsed dorsal root ganglia, with muchsmaller increases at later times after injury.The acute increase of IL-6 could originatefrom sensory cell bodies themselves, as hasbeen shown with IL-6 mRNA in situ hybridi-sation studies in rat sensory ganglia afterperipheral nerve injury,5 or from inflamma-tory cells. This increase may have autocrine/paracrine eV ects, which may aid cell survival,or have a role in sensory or sympatheticsprouting.

We conclude that IL-6 is a significantfactor in the events after nerve injury inhumans, particularly in sensory neurons. Thepotential therapeutic role in nerve repair forrecombinant human IL-6, and agents thatmodulate its action, deserves further investi-gation.

G SALDANHAK J BÄR

Y YIANGOUP ANAND

Division of Neuroscience and Psychological Medicine,Imperial College of School of Medicine,Area A,

Ground Floor, Hammersmith Hospital, Du CaneRoad, London W12 0NN, UK

R BIRCHT CARLSTEDT

Peripheral Nerve Injury Unit, Royal National Orthopaedic Hospital, Stanmore,Middlesex, UK

J M BURRI NSt Bartholomews and The Royal London School of

Medicine and Dentistr y,Queen Mary and Westfield College, Royal London Hospital, London, UK

Correspondence to: Professor P Anand

1 Hirota H, Kiyama H, Kishimoto T, et al . Accel-erated nerve regeneration in mice by upregu-lated expression of interleukin-6 and IL-6receptor after trauma. J E xp Me d 1996;183:2627–34.

2 Bolin LM, Verity AN, Silver JE, et al .Interleukin-6 production by Schwann cells andinduction in sciatic nerve injury. J Neurochem1995;64:850–8.

3 Bar KJ, Saldanha GJ, Kennedy AJ, et al . GDNFand its receptor component Ret in injuredhuman nerves and dorsal root ganglia. Neurore-

port 1998;9:43–7.

4 Anand P, Terenghi G, Birch R. et al . Endog-enous NGF and CNTF levels in humanperipheral nerve injury. Neuroreport 1997;8:1935–8.

5 Murphy PG, Grondin J, Altares M, et al . Induc-tion of interleukin-6 in axotomized sensoryneurons. J Neurosci 1995;15:5130–8.

Crossed face apraxia

Apraxia refers to the disorder of movementplanning and execution that cannot be

accounted for by motor or sensory deficitsnor by other cognitive impairments. Theterm apraxia encompasses several diV erentdeficits, including “face apraxia”, whichdefines the impairment of movements per-formed within the district of the cranialnerves. Group studies have shown that faceapraxia results from lesions of the lefthemisphere.1 However, a few cases can begleaned from the literature of patients whoseface apraxia followed lesions in their righthemisphere and was mentioned in fleetingcomments.2–4

Face apraxia has generally been equated tooral apraxia and tests aimed at assessing itonly comprise items exploring skilled move-ments of the lips, cheeks, and tongue.However, several early authors reported on

patients with face apraxia also showingmovement deficits of the eyes and eyebrows.5

Some anecdotal evidence of upper faceapraxia is also reported in more recentinvestigations. 6 We report on a patient,who, 2years after a right hemispheric lesion, showedsevere face apraxia for movements of both thelower and the upper parts of the face. A 55year old artist with 17 years of education hadan ischaemic stroke in August 1997. A seriesof CT and MR scans showed a rightfrontoparietal insular hypodensity also en-croaching on the anterior region of the rightinternal capsule and of the right deep nuclei,sparing the mesial and the anterior part of theparietal lobe. He had always been righthanded, scored 100% right handed on boththe Edinburgh handedness questionnaire7

and the 12 question handedness inventory.8

He also denied familiarity for left handed-ness. We examined the patient in October1999, 5 months after the end of his rehabili-tation therapy and more than 2 years after hisstroke. He still showed a severe left paresis,hemianopia, and a deficit of the lower facialnerve. No further deficits of the cranialnerves were seen. In particular, spontaneousmovements of the oculomotor nerves werenormal. The patient did not show generalcognitive impairment: his scores on intelli-gence tests were well within the normalrange. At the time of our assessment he didnot show clear evidence of visuospatialneglect which was mentioned in the clinicalnotes at onset. He performed flawlessly tasksassessing the ability to search for particular

targets, in reading, or in line bisecting,although he omitted a few left details incopying complex geometrical drawings. Dur-ing neurological examination the patientproved unable to close his eyes on verbalcommand. He failed even when the examinershowed him how to do it. He was thereforesubmitted to a battery of tests assessingapraxia including the upper and lower faceapraxia test.9 The nine upper and 29 loweritems of the test were performed first on imi-tation and then, considering the possibilitythat the patient could have some diYculty inperception, on verbal command. On imita-tion, the patient scored 2/45 and 320.25/435(adjusted scores) on the upper and lower face

IL-6 immunoreactivity in human nerve tissues. Assay concentrations of IL-6 in extracts of human nerve, comparing segments proximal and distal to injury with control postmortemnerve.

7.5

5.0

2.5

0.0

I L - 6 ( p g / m g )

Control Proximal Distal

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sections of the test respectively, both wellbelow the inner tolerance limit cut oV scores(38.43/45; 400.04/435). On command hefailed all items of the upper face test and hefailed the same items of the lower face testwhich he failed on imitation.

His errors were perseveration of the previ-ous item or substitutions with anothermovement—for instance, when asked tomake a clip-clop noise with his tongue, heshowed his teeth, then made his teeth chatter.Similarly, asked to close his eyes, he said“yes” at first, then he opened his mouth, thenhe tried to show his tongue. He was unable toclose either his right or his left eye, to lookleftward or rightward keeping his headmotionless, or to wrinkle his forehead or hisnose.

The patient’s face apraxia could not be dueto motor impersistence because he was notrequired to hold a position for a given time. 10

Moreover, the fact that his face apraxia waslong lasting excludes the possibility thatupper face apraxia has to be drawn back todiaschisis or other similar phenomena. Fi-nally, neglect had recovered at the time of testing and there was no cognitive deteriora-tion to account for the presence of this symp-tom.

Ideomotor apraxia was also assessed bymeans of a 24 item test.11 His score with theright arm and hand was normal (64/72, cutoV score=53). The patient was not aphasic;his language was emitted with a normalprosody, was well articulated, informative,and without qualitatively aphasic errors.

This case points to a possible role that theright hemisphere might have in normal facialpraxis, both for the lower and upper faceareas, in some people. Moreover, it confirmsthe dissociation between face apraxia andaphasia, as well as between limb and faceapraxia.

C PAPAGNODipartimento di Psicologia,

Università di Palermo, Italy

S DELLA SALA

Department of Psychology,King’s College,University of Aberdeen, AB24 2UB Aberdeen, UK

Correspondence to: Professor S Della [email protected]

1 De Renzi E. Apraxia. In: Denes F, PizzamiglioL, eds. Handbook of clinical and experimental neuropsychology. Hove: Psychology Press,1999:421–41.

2 Kleist K. Gehirnpathologie. Vornehmlich auf Grund der Kriegserfahrungen. (Brain pathologybased on war experience). Leipzig: JohanAmbrosius Barth, 1934.

3 Kramer JH, Delis DC, Nakada T. Buccofacialapraxia without aphasia due to a right parietallesion. Ann Neurol 1985;18:512–14.

4 Marchetti C, Della Sala S. On crossed apraxia.Description of a right-handed apraxic patientwith right supplementary motor area damage.Cortex 1997;33:341–54.

5 Lewandowsky M. Über apraxie des Lid-

schlusses. (About lid apraxia). Berliner KlinischeWochenschrift 1907;29:921–3.6 Lebrun Y. Apraxie de la parole et apraxia

bucco-faciale (Speech apraxia and oralapraxia). In: Le Gall D, Aubin G, eds.L’apraxie. Marseille: Solal, 1994:160–82.

7 Oldfield RC. The assessment and analysis of handedness: the Edinburgh Inventory. Neu-ropsychologia 1971;9:97–113.

8 Annett MT. The binomial distribution of right,mixed and left handedness. Q J Exp Psychol A1967;19:327–333.

9 Della Sala S, Spinnler H, Venneri A. Un test diaprassia della faccia: dati normativi e validazi-one su cerebrolesi sinistri e dementi diAlzheimer (A test of face apraxia: norms andvalidation with a sample of focal brain dam-aged patients and a sample of patients withAlzheimer’s disease). Archivio di Psicologia Neu-rologia e Psichiatria 2000 1998;49:346–57.

10 De Renzi E, Gentilini M, Bezzolli C. Eyelidmovement disorders and motor impersistencein acute hemisphere disease. Neurology 1986;36:414–18.

11 De Renzi E, Motti F, Nichelli P. Imitatinggestures: a quantitative approach to ideomotorapraxia. Arch Neurol 1980;37:6–10.

A case of BickerstaV ’s brainstem

encephalitis mimicking tetanus

BickerstaV ’s brainstem encephalitis is charac-

terised by acute ophthalmoplegia and ataxiawith progressive consciousness disturbance.1

Although BickerstaV described rigidity in therecovery phase,1 rigidity in the clinical courseof BickerstaV ’s brainstem encephalitis hasrarely been reported.2 We encountered a casein which the initial diagnosis was tetanus,because of the progression of severe rigidityand risus sardonicus, but which turned out tobe BickerstaV ’s brainstem encephalitis owingto the presence of anti-GQ1b IgG antibody.

A 23 year old man who had had no priorapparent infectious episode began to showdysaesthesia, clumsiness, and slight weaknessof all limbs (day 1). Due to rapid exacerba-tion of these symptoms he was admitted to ahospital the next day. On day 3, he becameirritable because of increased anxiety, al-

though he was alert and completely oriented.He was transferred to another hospital forfurther treatment. There he required assist-ance in walking because of new severe rigidityin all his limbs. Oral haloperidol (maximumdose 20 mg/day) was given for 10 days toreduce his anxiety, but his symptoms did notlessen. Treatment with intravenous methyl-prednisolone (1000 mg/day) from day 14 to16, as well as acyclovir (1500 mg/day) givenintravenously, failed to ameliorate his symp-toms. On day 17, he was transferred to ourhospital for further evaluation and treatment.

Physical examination on day 17 showed abody temperature of 37.0°C, blood pressure130/80 mm Hg, pulse rate 100 beats/min,respiratory rate 12 /min, and severe hyperhid-rosis. Neurological examination showed that

he was alert and well oriented. The pupilswere isocoric and round but mydriatic. Lightreflexes were prompt. Bilateral blephaloptosiswas present. Extraocular movement wascompletely inhibited vertically and horizon-tally. Restriction of mouth opening anddysarthria similar to risus sardonicus werecaused by increased tonus of the massetermuscles. Neither tongue atrophy nor fascicu-lation was present. Tests for muscle strengthand coordination could not be made due tosevere rigidity of the neck, trunk, and limbs.Deep tendon reflexes were absent, probablysecondary to the rigidity. The Babinskiresponse was negative bilaterally. Voluntarymovements were markedly slow, and sittingbalance was poor. Opisthotonus was notpresent. No abnormality was found in the

sensory examination. Because of Forley cath-eter placement due to the patient’s severegeneral condition, we did not evaluate hisbladder function.

White blood cell count was 13 320 /mm3

(84% neutrophils), but the erythrocyte sedi-mentation rate and C reactive protein con-centration were normal. Protein in CSF was144 mg/dl with normal cellularity. Nooligoclonal IgG bands were detected in theCSF. Magnetic resonance imaging detectedno abnormalities in the brain stem. An EEGwas normal. Motor nerve conduction veloci-ties and compound muscle action potentialsmeasured in the right median, ulnar, andposterior tibialis nerves were normal, but no

F waves were evoked. Antidromic sensorynerve velocity in the right median nerve wasnormal, but no sensory activation potentialswere evoked in the right ulnar and posteriortibial nerves.

Based on his clinical course and the physi-cal examination, the tentative diagnosis wasgeneral tetanus. On day 18, intravenous pip-eracillin sodium (4000 mg/day) and oral dan-trolene sodium (25–50 mg/day) were started.On day 19, 4500 IU human anti-tetanusimmunoglobulin (Tetanobulin®, Yoshitomi,Tokyo, Japan) was infused. On day 20, hisbilateral blephaloptosis and rigidity of thelimbs began to lessen. Subsequently hissymptoms and signs improved dramatically.On day 24 he could turn himself over in bed.On day 25 ophthalmoplegia was amelioratedwith slight limitation of lateral gaze. On day26 he could sit independently. On day 32 hecould stand without assistance, andon day 37he could walk independently. During therecovery phase, no ataxia was seen. He hasnot had a relapse for 2 years and 6 months.

After his recovery, we evaluated the anti-ganglioside antibodies and antitetanus anti-body activity in his serum. An enzyme linkedimmunosorbent assay3 showed that serumIgG on day 19 had high (4000) anti-GQ1b

antibody titre. The IgG antibodies did notreact with GM1, GM2, GD1a, GalNAc-GD1a, GD1b, or GT1b. Thin layer chroma-tography with immunostaining confirmedthat the patient’s IgG bound strongly toGQ1b, but not to GM1, GD1a, GD1b, orGT1b. No anti-GQ1b IgG antibody wasdetectable (titre<500) 2 years and 6 monthsafter the onset of neurological symptoms. Bycontrast, the neutralising antitetanus anti-body activity in the serum on day 17 was0.41–0.75 IU/ml, suYcient for protectionagainst tetanus infection.4

Serum anti-GQ1b IgG antibodies havebeen found in patients with Miller Fishersyndrome, Guillain-Barré syndrome withophthalmoparesis, acute ophthalmoparesis,and BickerstaV ’s brainstem encephalitis.5

Albumino-cytological dissociation in CSFand poor F wave response of the examinednerve are compatible with Miller Fisher orGuillain-Barré syndrome. The clinical find-ings, most characteristic of this patient, how-ever, were severe rigidity of the face, neck,trunk, and limbs, which has not beendescribed in Miller Fisher syndrome,Guillain-Barré syndrome, or acute ophthal-moparesis. The extrapyramidal side eV ect of haloperidol was unlikely because rigidity waspresent before the drug was administered.BickerstaV reported the development of par-kinsonism, including rigidity, within 2–4weeks of onset and during the recovery phasein BickerstaV ’s brainstem encephalitis, withthe exception of a fatal case in which parkin-sonism developed before maximal disability.1

Our patient showed rigidity from the begin-ning. Although an overlap of Guillain-Barrésyndrome could not be excluded,2 ourdiagnosis was BickerstaV ’s brainstem en-cephalitis, because the patient’s case wasclose to the exceptional one reported byBickerstaV . Antitetanus imunoglobulin iscomprised of high dose polyclonal IgGs totetanus toxin and other types of IgGs andIgMs, and it may have had an eV ect similar tothat of intravenous immunoglobulin in ourpatient. His dramatic recovery immediatelyafter antitetanus immunoglobulin adminis-tration could not be explained as part of anatural course. Although the mechanism forthe early appearance of rigidity in our


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reported case is not clear, BickerstaV ’s brain-stem encephalitis should be considered thediV erential diagnosis when rigidity, such astetanus, is present.

T SAITOI MIYAI

T MATSUMURAS NOZAKI

J KANGDepartment of Neurology,Toneyama National

Hospital 5–1–1Toneyama,Toyonaka, Osaka560–8552, Japan

H FUJITADepartment of Pediatrics, Osaka University Medical

School

N SUGIMOTODivision of Advanced Medical Bacteriology, Graduate

School of Medicine,Osaka University

N YUKIDepartment of Neurology,Dokkyo University School of

Medicine

Correspondence to: Dr Toshio [email protected]

1 BickerstaV ER. Brain stem encephalitis (Bicker-staV ’s encephalitis). In: Vinken P J, Bruyn G W,eds. Handbook of clinical neurology. Amsterdam:North Holland, 1978;34:605–9.

2 Yuki N, Wakabayashi K, Yamada M, et al . Over-lap of Guillain-Barré syndrome and Bicker-staV ’s brainstem encephalitis. J Neurol Sci

1997;145:119–21.3 Yuki N, Sato S, Tsuji S, et al . An immunologicabnormality common to BickerstaV ’s brainstem encephalitis and Fisher’s syndrome. J

Neurol Sci 1993;118:83–7.4 Kameyama S, Kondo S. Titration of tetanus

antitoxin by passive hemagglutination: I. titra-tion of guinea-pig antitoxins at various periodsof immunization. Japan J Med Sci Biol 1975;28:127–38.

5 Yuki N. Acute paresis of extraocular musclesassociated with IgG anti-GQ1b antibody. Ann

Neurol 1996;39:668–72.

Lysozyme in ventriculitis: a marker for

diagnosis and disease progression

The development of a hydrocephalus as atypical complication after subarachnoidhaemorrhage often requires implantation of a

catheter for drainage of ventricular fluid.Because this is an open system it carries a riskof development of bacterial ventriculitis bycontamination. This potentially life threaten-ing or neurologically disabling disease can bediagnosed by microbiological tests on theCSF. However, microbiological examinationis often not possible or shows pathologicalresults only after a delay, probably because of antibiotic prophylaxis. Standard CSF indicesare diYcult to interpret, because subarach-noid haemorrhage leads to an irritationsyndrome in the CSF, which can imitateinfection.

Lysozyme is a basic polypeptide of 129amino acids weighing 15 kDa, which is foundin neutrophilic granulocytes or monocytes,and is released from cytoplasmic and az-

urophilic granules.1

It is capable of degradingbacterial proteoglycans.2 Lysozyme showssignificantly higher concentrations in CSF inbacterial meningitis in comparison withabacterial meningitis, whereas in other dis-eases of the CNS much lower concentrationsare found.3 4

We retrospectively documented the resultsfrom 146 patients who underwent externalventricular drainage after subarachnoidhaemorrhage. As well as documenting thefrequency and timing of infection, themedical notes were inspected for risk factorsof infection.

In 64 patients (15 with microbiologicallyconfirmed ventriculitis, and 49 with no

evidence of ventriculitis) the following meas-urements were compared: serial CSF cytol-ogy; total protein; albumin; IgM, IgA, IgG;plasma/CSF ratio of albumin, IgM, IgA, IgG;locally produced fraction of IgM, IgA, IgGand CSF oligoclonal IgG, lactate, andglucose.

For further analysis, 61 CSF samples wereavailable from 14 patients with microbiologi-cally confirmed ventriculitis. As a control, weused one sample from each of 31 patients inwhom no evidence of ventriculitis was found.Immediately after these CSF samples hadbeen collectedfor clinical tests,the remainderof the samples had been frozen at−80°C.These CSF samples were investigated tomeasure their lysozyme concentrations byradial immunodiV usion. The sample is trans-ferred to circular wells in an agarose gel; theantigen then diV uses radially from the sampleinto the gel, which contains the correspond-ing antibody. After an incubation period (18hours) the antigen concentration can be readfrom a reference table (“The binding site”,Birmingham, UK).

For statistical analysis we used the 2 test,

the Wilcoxon matched pairs test, and aKaplan-Meier survival analysis. A pvalue<0.05 was considered to be statistically

significant.Fifteen of 146 patients (10.3%) developeda microbiologically established ventriculitis,confirmed by detection of pseudomonas aeru- ginosa (one case), staphylococcus epidermidis

(12 cases), gram negative rod cells (one case),and enterococci (two cases). The period of drainage was 3–39 days (mean 10 days).Infection rate was 3.5% (5/146) within the1st week, 5.3% (4/77) within the 2nd week,and 15.4% (6/39) after 2 weeks of drainage(p<0.02, df=2). Mean survival time (=noventriculitis) was 26 days. The probability of drainage without ventriculitis decreased to0.96 (SE 0.02) after 7 days, 0.86 (SE 0.045)after 14 days,0.66 (SE 0.1) after 22 days, and0.53 (SE 1.4) after 26 days. We identifiedpotential risk factors for ventriculitis in eight

of 15 patients with ventriculitis,and in nine of 131 patients without ventriculitis (p<0.001,df=1). The risk factors were: leakage in thedrainage system (26% with ventriculitis;8.4% without ventriculitis), disconnection(13.3%; 2.3%), blockage which was clearedby irrigation (20%; 5.3%), and dermal infec-tion (6.6%; 0%).

Comparison of the CSF results in 15patients who had established ventriculitiswith those in 49 patients without ventriculitisshowed no significant diV erence for most of the mentioned indices except the following.Ten of 15 patients with ventriculitis and onlyeight of 49 patients without ventriculitisshowed oligoclonal IgG in the CSF(p<0.001,df=1).Thirteen of 15 patients withventriculitis and 18 of 49 patients without

ventriculitis showed increased CSF-IgM (>7mg/l) concentrations (p=0.002, df=1). Thir-teen of 15 patients with ventriculits and 17 of 49 patients without ventriculitis showedincreased CSF lactate (>2.1 mmol/l;p<0.001, df=1).

In all 14 of the 15 patients with microbio-logically confirmed ventriculitis available foranalysis, maximal lysozyme concentrations of above 2.5 mg/l were found (mean 11.29 (SD8.1) mg/l, range 2.6–25 mg/l), in 61 samplesat diV erent times (figure). In only two of the31 control patients could lysozyme concen-trations just above 2.5 mg/l be detected, withall others lying clearly below this concentra-tion (mean 1.44 (SD 0.64) mg/l, range 0–2.6

mg/l, p<0.001, df=1). In 17 samples, theventricular concentration of lysozyme wascompared with the concentration in lumbarCSF samples takensynchronously. The meanratio of lumbar to ventricular concentrationwas 2.24 (SD 0.525) (range 1.4–2.8, 2 tailedp=0.0003, Wilcoxon matched pairs test).

Our study shows a clear connectionbetween the duration of drainage and the riskof ventriculitis. The indication for implantingor continuing ventricular drainage shouldtherefore be checked daily, and alternativessuch as catheter exchange should be consid-ered at an early stage. The documented riskfactors show that improving the standards of hygiene and nursing care are necessary forreduction of the risk of ventriculitis. Wefound the presence of oligoclonal IgG bands,CSF IgM,5 CSF lactate, and lysozyme in theCSF to be statistically relevant indices fordiagnosis. The finding that lysozyme concen-trations in lumbar CSF are more than twiceas high as in ventricular CSF has not to ourknowledge been described previously. Evi-dently lysozyme, as a relatively large proteinmolecule, is concentrated in the lumbar CSF.

The interpretation and the definition of nor-mal values must take account of thesefindings.

This study shows that a single, marginallypathological value has less diagnostic valuethan an increase in lysozyme detected in aseries of CSF samples. As a pragmaticapproach to early diagnosis of ventriculitis,we recommend a CSF analysis within the 1stweek, including measurement of lysozymeconcentration. If drainage is to be continuedlonger than 1 week, we would advise dailyCSF analysis, in particular of lysozyme. If there is a relative increase in lysozymeconcentration, ventriculitis should be as-sumed, even when microbiological findingsare still negative.

S SCHROEDER H J STUERENBURG

F ESCHERICHG PFEIFFER

Department of Neurology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246

Hamburg, Germany

F SCHROEDER Department of Neurosurgery

Correspondence to: Dr S Schroeder

1 Resnitzky P, Shaft D, Yaarrii A, Nir E. Distinctintracellular lysozyme content in normalgranulocytes and monocytes. A quantitativeimmunoperoxidase and ultrastructural immu-nogold study. J Histochem Cytochem 1994;42:1471–7.

Mean concentrations of lysozyme concentrationin ventriculitis during the 4 day periods around the detection of bacteria.

20

10

0

Day

Microbiologicalverificationof ventriculitis

M e a n c o n c e n t r a t i o n v e n t r i c u l a r

l y s o z y m

e i n v e n t r i c u l i t i s ( m g / l )

<1 1–5 6–10 >11

n=17mean

2.8

n=20mean

8.7

n=15mean

6.8

n=10mean

0.9


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2 Hoijer MA, de Groot R, van Lieshout L, et al .DiV erences in n-acethylmuramyl-l-alanineamidase and lysozyme in serum and cerebros-pinal fluid of patients with bacterial meningitis.

J Infect Dis 1998;177:102–106.3 Constantopoulos A, Zoumboulakis D, Kara-

boula K, et al . Cerebrospinal fluid and serumlysozyme activity in bacterial and viral menin-gits. Helvetica Pediatrica Acta 1977;32:217–20.

4 Firth G, Rees J, McKeran RO. The value of measurement of cerebrospinal fluid levels of lysozyme in the diagnosis of neurologicaldisease. J Neurol Neurosurg Psychiatry 1985;48:709–12.

5 Ribeiro MA, Kimura RT, Irulguit I, et al .

Cerebrospinal fluid levels of lysozyme, IgM,C-reactive protein in identification of bacterialmeningitis. Journal of Tropical Medicine and Hygiene 1992;95:87–94.

Clinicoanatomical correlates of a Fou

rire prodromique in a pontine

infarction

Pathological laughter heralding a neurologi-cal deficitwas first described by Ferré in 1903as Fou rire prodromique.1 2 We present a patientwith prodromal pathological laughter and aright pontine infarction in the territory of theparamedian branch of the basilar artery.These are the first clinicoanatomical corre-lates integrating MRI lesion mapping with

immunohistochemical studies for a serot-oninergic specific enzyme of human brainstems.

A right handed 61 year old woman wasadmitted to hospital for a left hemiplegia. Shepresented with a history of diabetes, highblood pressure, and an old myocardialinfarct. She had experienced spells of uncon-trolled and inappropriate laughter during thenight and the subsequent morning. At noon,her left side became paralysed. On admission,

she was alert, attentive, and had a right sixthnerve palsy and a left hemiparesis thatincluded the face. There was a left Babinski’ssign. Neuropsychological testing disclosed amild attentional deficit and a decreased pho-nological fluency. There was no lability of aV ect and no inappropriate crying. Sherecognised the laughter as abnormal. Thespells were usually totally inappropriate andwithout any associated mirth. Sometimesthey could be triggered by an unfamiliar situ-ation, such as talking to thephysicaltherapist.To measure pathological laughter with a vali-dated scale, we used the pathological laughterand crying scale3 (PLCS) and her score was15/27. A psychiatric evaluation was negativefor manic disorder. Brain MRI disclosed an

infarction in the right ventral pons withoutother focal lesion (figure, A). An EEG wasnormal. Spells of pathological laughter con-tinued for a week then gradually resolved.After 2 weeks, the PLCS score was 2/27.

The limits of the lesion in the right ventralpons were overlayed on a section of acorresponding level taken from a series of immunohistochemical preparations used tomap the entire human serotoninergicsystem.4 The main tracts and structuresinvolved are shown in the figure (B, C).

Pathological laughter is an exaggerated,uncontrollable, and inappropriate laughterusually unrelated to a true emotion or a con-gruent mood. It is found in gelastic epilepsy(ictal pathological laughter), associated withlesions in the hypothalamus, anterior cingu-late, or basal temporal lobe. Non-ictal patho-logical laughter is often associated withpathological crying and usually seen withbilateral, multiple cerebral lesions as acomponent of pseudobulbar palsy. However,non-ictal pathological laughter can occur inpatients with unilateral lesion, and withoutpseudobulbar palsy. In these cases, imagingstudies show lesions in the lenticulocapsular,thalamocapsular, and pontine base areas.Recognised causes include strokes or tu-

mours. Non-ictal pathological laughter mayalso occur in the cortical and subcortical ter-ritory of large arteries, usually the middlecerebral artery, and, in these cases, it may bevery diYcult to distinguish from a gelasticseizure. In prodromal pathological laughter,the locations of the lesions and the patholo-gies are similar, and include mainly strokesand tumours. The pathophysiology of patho-logical laughter was discussed by Wilson5 in1924, who suggested a motor release phe-nomenon. He pointed to an imbalancebetween voluntary motor pathways in thecorticobulbar tract and involuntary pathwaysfrom limbic circuits to the facial nervenucleus, the nucleus ambiguous, and anteriorhorn cells that subserve the phrenic nerve(faciorespiratory coordination of laughter).

Another hypothesis involves serotoninergicneurotransmission, originating in the pontineserotoninergic raphe nuclei.Pharmacologicalevidence also shows that serotonin reuptakeinhibitors may improve a patient’s laughter.3

The raphe nuclei are divided in a rostraland a caudal group.4 Nuclei of the rostralgroup, in the midbrain and rostral pons,project rostrally to the forebrain. They areseparated by a gap from the nuclei of the cau-dal group extending from the caudal pons tothe end of the medulla. These nuclei projectto the entire brainstem and spinal cord. Sero-toninergicneurons of the caudalpons lying inthe ventral tegmentum belong to the raphenucleus magnus (RMg), and are at the originof a widespread innervation of brainstemstructures.

Our patient presented with prodromalpathological laughter heralding an infarctionin theright ventral pons,in theterritory of theparamedian branch of the basilar artery. Shehad no other signs of pseudobulbar palsy. It isunlikely that pathological laughter in our casewas due to seizures (gelastic epilepsy) be-cause of the long duration of the episodes,theabsence of altered sensorium, automatisms,or EEG abnormalities, and the location of thestroke. The unique and circumscribed lesionof the corticospinal and corticobulbar tractsat the level of the ventral pons, saving themedial lemniscus, may seem to favourWilson’s hypothesis; however, the posteriorangle of the lesion along the midline also

Axial views at the level of the sixth nerve and the middle cerebellar peduncle in the pons. (A) MRI showing the infarct in the right ventral pons. Box area depicted in (B). (B) Micrograph of a humanbrainstem transverse section at the level corresponding to the MRI, immunostained for a serotoninspecific enzyme. The limit of the infarct is overlayed, with respect to the reference structures:( N )=medial lemniscus; CT=corticospinal and corticobulbar tracts; MCP=medial cerebellar peduncles.(C) Enlargment of the boxed area in (B), showing the location of the raphe nucleus magnus (RMg)relative to the medial lemniscus. Scale bars: (A) 1000 µm, (B) 500 µm, (C) 250 µm.


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involves the serotoninergic RMg (figure,A-C). An involvement of this serotoninergicnucleus is further supported by the temporalcharacteristics of pathological laughter, oc-curing in transient bursts before the develop-ment of motor signs in the limbs. Wetherefore conjecture that pathological laugh-ter was prodromal because ischaemia beganat the distal end of the vascular territory of the paramedian branch of basilar arteryinvolving the RMg first. Both hypothesescould be reconciled if we assume thatemotional motor pathways can be modulatedby serotononergic neurotransmission fromthe raphe nuclei. A small lesion involvingconvergence of both emotional motor path-ways and raphe nuclei would also explain thelocation of prodromal pathological laughterin the pons.

FRÉDÉRIC ASSAL NATHALIE VALENZA

THEODOR LANDISDepartment of Neurology,HUG, 24 rue

Micheli-du-Crest,CH-1211 Geneva, Switzerland

JEAN-PIERRE HORNUNGIBCM, Faculty of Medicine, 1005 Lausanne,

Switzerland

Correspondence to: Dr Frédéric [email protected]

1 Féré C. Le fou rire prodromique. Rev Neurol 1903;11:353–8.

2 Wali GM. Fou rire prodromique heralding abrainstem stoke. J Neurol Neurosurg Psychiatry1993;56:209–10.

3 Robinson RG, Parikh RM, Lipsey JR, et al .Pathological laughing and crying followingstroke: validation of a measurement scale and adouble-blind treatment study. Am J Psychiatry1993;150:286–93.

4 Törk I, Hornung JP. Raphe nuclei and the sero-toninergic system. In: Paxinos G, eds. Thehuman nervous system. San Diego: AcademicPress, 1990:1001–22.

5 Wilson SAK. Some problems in neurology, II:pathological laughing and crying. J Neurol Psy-chopathol 1924;16:299–333.

Proximal median mononeuropathy

associated with an anomalous deepcourse through the brachialis muscle

Proximal median mononeuropathies, unre-lated to direct trauma or external compres-sion, are unusual in neurophysiological prac-tice; several syndromes have been morecommonly described including the anteriorinterosseus syndrome, the pronator teres syn-drome, and entrapments at the lacertusfibrosus or at the ligament of Struthers.1

We report the case of a 29 year old womanwith an upper median mononeuropathy at anunusual lesional site. She started a new jobconsisting of repeatedly lifting heavy cratesfull of apples from the ground, carrying themfor a while, and then putting them on a shelf.Fifteen days later, at the end of a working day,

she began to complain of right hand weaknesswith numbness and tingling limited to thefirst, second, and third fingers; 4 weeks afterthe onset of symptoms neurological examina-tion showed marked weakness of thumbabduction and opposition, forearm prona-tion, and flexion of the wrist and of the distalphalanges of the thumb and index finger; shehad paraesthesias on the palmar side of theright thumb, index, and middle fingers with-out spontaneous pain, which could otherwisebe strongly evoked by deep palpation of themedian nerve trunk at the lower third of theright upper arm. The patient denied any kindof trauma or prolonged direct compressionon that limb.

Electromyography showed fibrillation po-tentials and neurogenic motor units recruit-ment in all forearm right median innervatedmuscles, including the pronator teres; inthenar median innervated muscles abundant

fasciculations and severely reduced recruit-ment patterns were the major findings, withminimal denervation; on nerve conductionstudies the distal right median cMAP had alatencyof 4 ms and a positiveto negativepeakamplitude of 25 mV; antidromic SNAPrecorded at the third finger had an onsetlatency of 3.6 ms and a positive to negativepeak amplitude of 70 µV; forearm medianmotor and sensory conduction velocitieswere54 m/s and 60 m/s respectively; stimulation of the median nerve at more proximal sites dis-closed a partial motor (fig 1 (A)) andcomplete sensory (fig 1 (B)) conductionblock in the distal third of the upper arm; aninching technique allowed better localisationof the site of conduction block about 9 cmproximal to the elbow along themedian nerve

course. The rest of the neurophysiologicalstudy, performed in four limbs, was normal.Routine blood chemistry was normal, includ-ing tests for diabetes, thyroid function, andvasculitis. A study of DNA excluded thepresence of the deletion at chromosome17p11.2-p12.

Radiography of the right humerus ruledout a supracondylar process; an MRI studyof the right upper arm using T1 weightedaxial images along the nerve course showedthe median nerve to be normally recognis-able within the arm neurovascular bundleabove the lesional site (fig 2 A); following thenerve course in more distal sections thenerve seemed to separate from the bundle asit approached the belly of the brachialismuscle (fig 2 B). In the subsequent more

distal sections the nerve was no longerrecognisable within the image of the brachia-lis muscle belly (fig 2 C). At surgicalexploration of the right median nerve, theproximal segment seemed to be locatedwithin the neurovascular bundle in a deepinferolateral position. At the transition be-tween the middle and the distal third of thearm, where the basilic vein joined thehumeral vein, the nerve was found to turndeeply through the brachialis muscle bellyfrom which it emerged about 5 cm more dis-tal. Muscle fibres covering the nerve weresectioned allowing appraisal of a consistentreduction of the size of the nerve throughoutits intramuscular course. No other abnor-

malities were detected along the nerve untilit entered the antecubital fossa (fig 2 C).

Neurolysis was followed by clinical andneurophysiological improvement. Fifteendays after surgery hand function improved; 2

years later there was no weakness and EMGwas consistent with a good reinnervationprocess.

Our patient presented a subacute uppermedian mononeuropathy in the distal third of the upper arm associated with an anomalousintramuscular course through the brachialismuscle; this was documented by neurophysi-ological investigation, imaging studies, andsurgical exploration. To our knowledge this isthe first report of a median nerve lesion atthat site associated with such anatomicalfindings.

Anatomical variations involving the courseor the structure of muscles and nerves andtheir relations are reported as not uncommonin cadaveric dissection studies of the upperlimbs2; as these anatomical variations are

rarely associated with peripheral nerve le-sions, their pathophysiological relation re-mains somehow unclear.

For the proximal upper arm Bellmann andVellander3 described an isolated case of median nerve compression at its origin by ananomalous muscle band originating from theinterval between the subscapularis and latis-simus dorsi muscles and crossing the neuro-vascular bundle to reach the anterior surfaceof the humerus.

In the distal upper arm and elbow regionthe presence of a supracondilar ligament andthe variable relation of the median nerve withthe heads of the pronator teres muscle areindeed the most often reported situationspredisposing to an entrapment.

A few authors have described even more

uncommon anatomical variations atnecropsy, discussing their potential role incausing a focal median nerve lesion. Dharap4

described a case showing an anomalous mus-cle arising from the humerus and crossing themedian nerve andthe brachial artery to blendwith the common origin of the forearm flexormuscles. Nakatani et al 5 reported a case inwhich a muscle slip from an anomalous fourheaded biceps brachii muscle joined the pos-terior fascia of the pronator teres forming atunnel where the median nerve seemed to becompressed.

At the forearm level the median nerve maybe compressed by an anomalous palmarislongus muscle or in the hand by anomalous

Figure 1 Neurophysiological study: (A) motor and (B) sensory inching of the r ight median nerveacross the site of conduction block; the drop of motor and sensory potentials at l atencies 9.8 and 8.3ms respectively corresponded to a stimulation site located along the nerve course about 9 cm proximal to a line between the biceps tendon and the medial epicondyle; recordings from the abductor brevis pollicis muscle by surface electrodes in (A) and from the third finger by r ing electrodes in (B).

A B5 ms 2 ms

5 mV 20 µV


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lumbrical or thenar muscles6; similar casesmay involve the ulnar and the superficialradial nerves.

The pathophysiology of this type of lesionis mainly mechanical: a repeated and pro-longed compression may develop eitherdirectly by the contracting muscle itself or byfixation against more rigid osteoligamentous

tissues; the movements performed by ourpatient consisted in repeated and alternatedelbow flexions and extensions under loading:in this setting the contracting muscle couldalso have reduced or blocked the longitudinalsliding of the nerve along its bed, with subse-quent stretching and friction of the nervetrunk.7

In conclusion, this case emphasises thatrare anatomical variations should be consid-ered in the diV erential diagnosis of proximalmedian mononeuropathies at uncommonlesional sites.

This work was presented in abstract form at theannual meeting of the Italian Society of ClinicalNeurophysiology-Trieste, Italy, October 3–6 1998.

ALBERTO MORINI

LAURA VIOLADANIELE ORRICODepartment of Neurology, Santa Chiara Hospital,

Largo medaglie d’oro no1, 38100 Trento,Italy

GIORGIO BIANCHINIDepartment of Orthopaedic Surgery

WALTER DELLA SALADepartment of Radiology

ALESSANDRO D GHOBERTDepartment of Rehabilitation

Correspondence to: Dr Alberto [email protected]

1 Gross PT, Royden Jones H Jr. Proximal medianneuropathies: electromiographic and clinicalcorrelation. Muscle Nerve 1992;15:390–5.

2 Lahey MD. Anomalous muscles associated withcompression neuropathies. Orthopaedic Review1986;4:199–208.

3 Bellmann S, Velander E. Neurovascular distur-bance of unusual origin in the arm. Acta Chiru-rgica Scandinavica 1963;125:199.

4 Dharap AS. An anomalous muscle in the distalhalf of the arm. Surg Radiol Anat 1994;16:97– 9.

5 Nakatani T, Tanaka S, Mizukami S, et al . Bilat-

eral four-headed biceps brachii muscles: themedian nerve and the brachial artery passingthrough a tunnel formed by a muscle slip fromthe accessory head. Clin Anat 1998;11:209–12.

6 Bang H, Kojima T, Tsuchida Y, et al . A case of carpal tunnel syndrome caused by accessorypalmaris longus muscle. Handchir Mikrochir Plast Chir 1988;3:141–3.

7 Mc Lellan DL, Swash M. Longitudinal slidingof the median nerve during movements of theupper limb. J Neurol Neurosurg Psychiatry1976;39:566–70.

Documented growth of a temporal

arachnoid cyst

Most arachnoid cysts are probably present atbirth, or develop soon after. Once they areformed, they are thought to remain stable,

apparently in some kind of equilibrium withthe rest of the intracranial space. Notinfrequently, cysts have been reported to dis-appear spontaneously (for references seeWester and Hugdahl1) and a minority maygrow with increasing age, although ratherslowly.2 Occasionally, cysts in infants havebeen reported to grow to a substantial size.Kumagai et al. 3 reported on a newborn boywho developed a temporal fossa cyst betweenthe age of 2 and 4 months, which laterincreased considerably before it was removedwhen the patient was 8 months old.

Except for the very smallest, most arach-noid cysts display radiological signs indicat-ing an increased intracystic or intracranial

pressure. For example, during infancy andearly childhood, cysts may influence theshaping of the adjacent skull bone, in the caseof middle fossa cysts resulting in an enlargedfossa, often with a bulging of the overlyingbone. Moreover, middle fossa cysts may alsodislocate the temporal lobe posteriorly, andlarger cysts regularly cause a midline shift,

thus indicating expansive forces.This notion of raised intracystic and

intracranial pressures is supported by thecommon intraoperative finding of a cyst wallbulging out of the dural incision. However,the relative paucity of associated symptoms,the moderate radiological displacement, theabsence of perifocal oedema in the adjacentbrain parenchyma, and, finally, the totalintraoperative impression,all indicate that thepressure is only moderately increased.

It is a common clinical experience that thesymptoms caused by an arachnoid cyst mayfirst present after many years, and that thesymptoms also may vary over time. Why thisis so is not known, but it is tempting tosuggest variations in the intracystic pressure

as one explanation.The demonstration of a cyst enlargementover time may be of some importance, as itwould provide additional evidence of anincreased intracysticpressure,and that arach-noid cysts not merely represent passive accu-mulations of fluid as implied by the term “thetemporal lobe agenesis syndrome”.4 With theexceptions mentioned above, results fromvery few patients have been published thatshow growth of an arachnoid cyst. We herebyreport on one such patient.

An 18 year old man had CT at the age of 8because of complaints thought to be causedby a sinusitis (a moderate transitory head-ache) and no other symptoms. It was then

Figure 2 Anatomical study. Top: T1 weighted MR axial images of the distal right upper arm across the lesional site;(A): proximal;(B): intermediate; (C):distal section.Left: surgical findings (D); brachialis muscle fibrescovering the median nerve have been sectioned;note theanomalous deep course of the median nerve trunk (small white arrow) apart from the vascular bundle (large whitearrow) and through the brachialis muscle belly (blackarrow).See text for details.


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discovered that he had a relatively smallarachnoid cyst in the left temporal fossa.The cyst did not reach above the sphenoidalwing or the pyramid (figure A and B). As weat that time were not yet aware of the cogni-tive impairment caused by most temporalcysts,1 we refrained from surgical decom-pression.

Ten years later, he was referred to us again,nowcomplainingof a strong, episodic,frontal

headache that had developed over the pastyear. The strength of the headache variedwith body position; it increased when he wasleaning forward, and was relieved when hewas resting on his back. New CT (figure Cand D) showed that the cyst had grown con-siderably. At the age of 8, the cyst volume was6.5 ml, as calculated from the films. Duringthe next 10 years, the cyst volume nearly tri-pled, measuring 18.3 ml when he was 18years of age.

The total intracranial volume was calcu-lated to be 1485 ml on both occasions, withno skull growth occurring between the agesof 8 and 18 years. Also the size of the twomiddle cranial fossae remained practically

unchanged during the same period. The sizeof each fossa was calculated from the films,using a standardised technique based on thebony landmarks surrounding it. The rightfossa was calculated to contain 19 ml on bothoccasions, and the somewhat larger left fossashowed a non-insignificant increase, from 24ml to 24.7 ml.

The patient was operated on under generalanaesthesia, with craniotomy, removal of cyst

membranes, and fenestration to the basal cis-terns. Postoperatively, the left temporal lobeexpanded and completely filled the space thathad been occupied by the cyst. Thus, the cystdisappeared, and so did his headache. He hasnow been followed up for 23 months aftersurgery, without reproduction of the cyst orthe headache.

The patient presented here displayed aconsiderable growth of a temporal arachnoidcyst as seen on two scans 10 years apart. Wedo not know exactly when the growth tookplace, but it is tempting to correlate it withthe increased symptoms (mainly headache)evolving over the past year before thesecond CT. In retrospect it is possible, or

even probable, that the patient’s headacheat the age of 8 also was caused by the cyst,and not a sinusitis. The increase in cysticvolume must have occurred after the neuro-cranium had become relatively rigid, as thepatient was already 8 years old before thedocumented growth started, and the totalintracranial volume as well as the volume of the left middle fossa remained constantover the 10 years. Therefore, the cyst growthmust have occurred at the expense of brain tissue or the CSF compartment, andcannot be ascribed to a soft, yielding skullallowing an unrestrained growth of theunderlying cyst, as we may occasionally seein infants, and as was reported by Kumagaiet al .3

Thus, the present finding may be taken asan indication that temporal arachnoid cystsare not merely passive accumulations of fluid,andthat thecysticgrowth in this patient musthave been caused by an increased intracysticpressure that was suYcient to widen thesylvian fissure, and to dislocate the temporallobe. In previous studies, it has been shownthat this eV ect on the temporal lobe issuYcient to cause cognitive dysfunction, withpostoperative improvement when the cyst issurgically decompressed.1–5 In our opinion,such findings alone may constitute a suY-cient indication for surgery, but only if thecomplication rate can be kept at a negligiblelevel.

K WESTER Department of Neurosurgery

G MOENDepartment of Radiology, Neuroradiological Section,

University of Bergen Medical School, Haukeland University Hospital, N-5021 Bergen, Norway

Correspondence to: Dr Knut Wester

1 Wester K, Hugdahl K. Arachnoid cysts of the left temporal fossa: impaired preoperativecognition and postoperative improvement.

J Neurol Neurosurg Psychiatry 1995;59:293–8.2 Becker T, Wagner M, Hofman E, et al . Do

arachnoid cysts grow? A retrospective CTvolumetric study. Neuroradiology 1991;33:341– 5.

3 Kumagai M, Sakai N, Yamada H, et al . Postna-tal development and enlargement of primarymiddle cranial fossa arachnoid cyst recognizedon repeat CT scans. Childs Nerv Syst 1986;2:211–5.

4 Robinson RG. The temporal lobe agenesis syn-drome. Brain 1964;87:87–106.

5 Soukup VM, Patterson J, Trier TT, et al . Cogni-tive improvement despite minimal arachnoidcyst decompression. Brain Dev 1998;20:589– 93.

Pituitary apoplexy presenting as

massive subarachnoid haemorrhage

Pituitary apoplexy is an uncommon, but wellrecognised clinical syndrome, which usuallyresults from ischaemic or haemorrhagicnecrosis of a pituitary adenoma.1 It is charac-

terised by the abrupt onset of severe head-ache, visual impairment, ophthamolplegiaand often, a deteriorating level of consciousness.2 Signs of meningeal irritationare frequent accompaniments, which mayconfuse the clinical picture with that of aneu-rysmal subarachnoid haemorrhage (SAH).We report a case of massive SAH caused bypituitary apoplexy and present the CT andMRI findings.

A 72 year old woman, with nothing in herhistory to suggest pituitary dysfunction,presented with the abrupt onset of severeheadache, vomiting, and gradually deteriorat-ing level of consciousness. A CT examinationof the brain without contrast enhancement

(A and B) Axial CT when the patient was 8 years old, showing a small arachnoid cyst in the left middle fossa. (C and D) Axial CT when the patient was 18 years old, showing that the cyst in the left middle fossa had grown considerably, now reaching well above the sphenoidal wing.


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showed an extensive basal subarachnoidhaemorrhage that had diV used into both syl-vian fissures and into the sulci over theconvexity of the cerebral hemispheres. Inaddition there was a rounded heterogeneousdensity mass in the suprasellar cistern (fig 1A). After the administration of contrastmaterial the lesion displayed heterogeneouscentral enhancement (fig 1 B.) A rupturedanterior communicating aneurysm was sus-pected but was excluded by normal cerebralangiography.

Brain MRI confirmed haemorrhage withina pituitary tumour (fig 2 A). It could also beseen that the haemorrhage had rupturedthrough a defect in the tumour capsule intothe subarachnoid space (fig 2 B). Despite theadministration of 100 mg hydrocortisoneintravenously every 6 hours and cardiopul-monary support her condition progressivelyworsened and she died 3 days after admis-sion.

The clinical syndrome of pituitary apo-plexy evolves within hours to days.2 Thesymptoms vary from mild to severe and canprogress rapidly to coma and death. Becausemany patients are unaware that they harboura pituitary tumour,pituitary apoplexy is oftenunrecognised at presentation. In pituitaryapoplexy, blood and necrotic tumour tissueare enclosed and compressed within the con-fined space of the sella turcica, a region that isin close anatomical proximity to the basal cis-terns. When the pressure gradient within thesella exceeds the resistance of the surround-ing structures, blood is expelled into the sub-arachnoid space producing a clinical picturethat may be indistinguishable from aneurys-mal SAH.3 Thus pituitary apoplexy must beincluded in the diV erential diagnosis of “angiographically negative” SAH.4 Brain CTis the modality of choice in the initial investi-gation of SAH. It will show the spread andseverity of the haemorrhage within the

subarachnoid space, as well as any extensioninto the brain.1 When pituitary apoplexy isthe cause, CT will usually show the pituitarytumour as well as any recent haemorrhage.Brain MRI is superior to CT in identifyingthe tumour as well as the associated haemor-rhage or infarction. In the case presentedhere, the enhanced MRI also displayed thedefect in the tumour capsule which repre-sented the site of rupture. The managementof pituitary apoplexy includes the immediateadministration of high dose corticosteroids tocombat adrenal insuYciency. When there israpid deterioration of visionor a progressivelyworsening level of consciousness, urgent sur-gery in the form of trans-sphenoidal decom-pression should be carried out.

MOHAMMED AL WOHAIBINEVILLE A RUSSELL

AHMED AL FERAYANDivision of Neurosurgery, King Fahad National

Guard Hospital,PO Box 22490, Riyadh 11426,Saudi Arabia

ADNAN AWADAMOHAMMED AL JUMAH

Division of Neurology

MATTHEW OMOJOLADepartment of Diagnostic Imaging

Correspondence to: Dr Neville A Russell

1 Bills DC, Meyer FB, Laws ER, et al . Aretrospective analysis of pituitary apoplexy.

Neurosurgery 1993;33:602–9.2 Cardoso EB, Peterson EW. Pituitary apoplexy: a

review. Neurosurgery 1984;14:363–73.3 Chen ST, Chen SD, Ryu SJ, et al . Pituitary apo-

plexy with intracerebral hemorrhage simulatingrupture of an anterior cerebral artery aneu-rysm. Surg Neurol 1988;29:322–5.

4 Gabriel JE, Rinkel GJE, Van Gijn J, et al .Subarachnoid hemorrhage without detectableaneurysm. A review of the causes. Stroke 1993;24:1403–9.

Early detection of non-compliance in

Wilson’s disease by consecutive copper

determination in cerebrospinal fluid

A 41 year old technical employee was

diagnosed with Wilson’s disease in 1982, 2yearsafter onset of dysarthria,diplopia,visualdeficits, ataxia, and concentration deficits.The patient improved rapidly withd -penicillamine and a copper free diet, andhas since returned to normal neurologicalfunction. Penicillamine was stopped in 1989and he changed his diet from copper free to anormal diet in 1987. In 1990 he was put on800 mg zinc a day. During the past 17 yearshe underwent 20 determinations of copperconcentration in CSF for follow up of treatment (figure) as copper concentrationsin CSF can be used as an indicator of braincopper concentration in the cerebral manifes-tation of Wilson’s disease.1–5

Copper was measured by flameless atomicabsorption (Perkin Elmer, HGA 500, Über-

lingen, Germany). The main resonance linewas 324.7 nm with deuterium backgroundcompensation and argon as a protective gas;the sample volume was 20 µl using anautosampling system. The CSF wasmeasured undiluted. The patient was nowagain routinely admitted for monitoring of the eYciency of the treatment. He was free of complaints and the neurological examina-tion as well as a neuropsychological test bat-tery and visually evoked potentials were nor-mal. He explicitly denied any change in dietor drug therapy (zinc, 800 mg a day). Wefound, however, an almost threefold increaseof his CSF copper concentration comparedwith the previous values (figure). Serum

Figure 1 (A)Cranial CT without contrast, showing a heterogeneous but mostly high density mass inthe suprasellar cistern (arrowheads). There is also extensive subarachnoid haemorrhage. (B) Cranial CT with contrast, showing central enhancement within a heterogenous high density mass(arrowheads).

Figure 2 (A) Coronal T1 weighted MRI, showing suprasellar extension of a sellar mass. The area of high intensity signal (arrow) represents methaemoglobin within clotted blood. Note also thehyperintense tumour rim. (B) Contrast enhanced sagittal MRI T1 weighted image,showing that thebulk of the mass is isointense with brain. There is a defect posteriorly in the superior aspect of thecapsule representing the site of rupture (arrow).


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copper and coeruloplasmin were unchanged.Confronted with these results the patientadmitted that he had been non-adherentto his zinc regimen for the past 2 years

by reducing the daily zing intake to lessthan 400 mg a day. One established param-eter for the eYcacy of treatment in Wilson’sdisease is the balancing of the intake andexcretion of copper. This, however, was notfeasible as the patient refused to take astandardised diet, rendering the daily copperintake unknown. As is displayed in the figurethere had been a continuous decrease of theCSF copper concentrations over the pastyears, although the treatment consisted onlyof 800 mg zinc a day without a restriction incopper intake. The repeated determinationof the CSF copper allowed for the demon-stration of a suYcient treatment and forthe detection of non-adherence to the treat-ment regimen before the reappearance of

clinical symptoms. We conclude that thedetermination of CSF copper reliably de-tects copper accumulation in the CNS andmay be used to monitor the treatmenteYcacy, particularly in patients with non-adherence to (copper free) diet and drugtreatment.

HANS JOERG STUERENBURGCHRISTIAN EGGERS

Neurological Department, University Hospital

Hamburg-Eppendorf, Martinistrasse 52, 20246

Hamburg, Germany

Correspondence to: Dr H J [email protected]

1 Weisner B, Hartard C, Dieu C. CSF copperconcentration: a new parameter for diagnosis

and monitoring therapy of Wilson’s diseasewith cerebral manifestation. J Neurol Sci 1987;79:229–37.

2 Kodama H, Okabe I, Yanagisawa M, et al . DoesCSF copper level in Wilson disease reflect cop-per accumulation in the brain. Pediatr Neurol 1988;4:35–7.

3 Hartard C, Weisner B, Dieu C, et al . Wilson’sdisease with cerebral manifestation: monitor-ing therapy by CSF copper concentration. J

Neurol 1993;241:101–7.4 Stuerenburg HJ, Kunze K. Determinants of the

copper concentration in CSF. J Neurol Neuro-surg Psychiatry 1999;67:252–3.

5 Stuerenburg HJ. CSF copper concentrations,blood-brain barrier function and coerulo-plasmin synthesis during the treatment of Wilson’s disease. J Neural Transm 2000;107:321–9.

CORRESPONDENCE

Between will and action

I read with great interest the recent paper byBundick and Spinella1 and the related

commentary by Goldberg.

2

These articlesaddress the neurological substrates of voli-tional disturbance and in places they adoptthe vocabulary of the philosophy of action— for example, Goldberg refers to the “will”.However, their uses of action related termsare mutually inconsistent and some clarifica-tion might assist in elucidating the functionalanatomical relevance of the disorders de-scribed.

If we are to use the terms “will” and“action” then their use should be internallyconsistent. The “will” is that process thatdeliberates (consciously) on what is to bedone, and the “action” is the performance,which follows on from that deliberation.3 4 (Itshould be noted that the temporal sequenceof this philosophical model of volition is sub-

stantially undermined by the classic EEGexperiments of Libet et al on “intention”.5 6)An “action” is consciously chosen;there is nosuch thing as an “involuntary action” (ac-cording to this model). Involuntary move-ments are movements not the intended actions

of the agent (“the one who acts”).4 It followsthat the movements initiated by an “alienhand” may seem purposeful, but they are notactions (chosen by the patient). They are fail-ures of action in so far as the patient cannotmake the limb “behave”. Hence, althoughGoldberg refers to the “will” being involvedin action generation, his terminology isextrapolated inconsistently: he refers to alienhands performing “purposeful acts” and“involuntary actions”2; the first is an attributeof an agent, the second is an oxymoron.4

Bundick and Spinella, by contrast, refer to“involuntary motor activity” and “non-purposeful” movements.1 These terms arecoherent within the context of the “will”vocabulary being used.

The above points are not merely pedantic,as a case can be made for “action” and“agency”implicating diV erent brainsystems,7

and thus the volitional deficit demonstratedin each form of the alien hand syndrome mayhave some cognitive-neurobiological rel-evance.

In the medial-prefrontal and callosal formsof alien hand syndrome, the patients, al-though they have a failure of motor control,and an inability to impose their “will” on thealien limb, do not generally attribute alienagency to that limb—that is, they do not

experience it as belonging to an “other”.However, in the posterior alien hand syn-drome, personal agency may be lost, and thelimb experienced as belonging to someoneelse. Consider the case of Leiguarda et al ,8

cited by neither Bundick and Spinella norGoldberg.1 2 This alien limb (associated withictal activity from a right parietal lesion) wasexperienced thus by the patient:

”Suddenly I had a strange feeling on myleft side; later I could not recognize the leftarm as my own; I felt it belonged to someoneelse and wanted to hurt me because it movedtowards me”.8

This third form of alien hand syndrome hasbeen referred to previously.7 The loss of

agency it comprises is consistent with thatalienation noted in “somatoparaphrenia” byCritchley9 and is congruent with that attribu-tion of agency to external forces so character-istic of schizophrenic “alien control”; itself associated with functional abnormality of theright parietal region.10

Hence, a consistent application of actionterminology may help to elucidate thefunctional anatomical correlates of disordersof volition.7

S A SPENCE Academic Department of Psychiatry,University of

She Yeld,The Longley Centre,She Yeld S5 7JT, UK

1 Bundick Jr T, Spinella M. Subjective experi-ence, involuntary movement, and posterioralien hand syndrome. J Neurol Neurosurg Psychiatry 2000;68:83–5.

2 Goldberg G. When aliens invade: multiplemechanisms for dissociation between will andaction. J Neurol Neurosurg Psychiatry 2000;68:7.

3 Dilman I. Free will: an historical and philosophical introduction. New York: Routledge, 1999.

4 Macmurray J. The self as agent . London: Faberand Faber, 1991.

5 Libet B, Gleason CA, Wright EW, et al . Time of conscious intention to act in relation to onset of cerebral activity: readiness-potential. Brain1983;106:623–42.

6 Spence SA. Free will in the light of neuropsy-chiatry. Philosophy, Psychiatry and Psychology1996;3:75–90.

7 Spence SA, Frith CD. Towards a functionalanatomy of volition. Journal of Conscious Studies1999;6:11–29.

8 Leiguarda R, Starkstein S,Nogues M, et al . Par-oxysmal alien hand syndrome. J Neurol Neuro-surg Psychiatry 1993;56:788–92.

9 Critchley M. The parietal lobes. New York:Hafner Press, 1953.

10 Spence SA, Brooks DJ, Hirsch SR, et al . A PETstudy of voluntary movement in schizophrenicpatients experiencing passivity phenomena(delusions of alien control). Brain 1997;120:1997–2011.

Progressive dementia and gait disorder

in a 78 year old woman

Although the provisional diagnosis of glioma-tosis cerebri in the clinicopathological case con- ference by Tagliati et al was the one eventuallyvalidated at necropsy,1 the discussion shouldalso have entertained the possibility that theoccurrence of signal hyperintensity on MRI,in the context of dementia, ataxia, andBabinski’s sign could also be consistent withthe diagnosis of cerebral amyloid angiopathy(with giant cell inflammatory reaction toB4-amyloid and vasculitis), exemplified by a63 year old man presenting with some of these stigmata.2 In the classic triad, consistingof cognitive impairment,upper motor neuronsigns, and lobar haemorrhage,3 the thirdmight well be a criterion potentially inter-changeable with, or antedated by amyloidrelated vasculitis and attendant stigmata suchas focal non-specific hyperintensity on MRI.

O M P JOLOBEDepartment of Medicine for the Elderly, Tameside

General Hospital,Fountain Street, Ashton under Lyne,OL6 9RW, UK

1 Tagliati M, Perl DP, Drayer B, et al . Progressivedementia and gait disorder in a 78 year oldwoman. J Neurol Neurosurg Psychiatry2000:68:526–31.

2 Caplan LR. Case 10–2000. N Engl J Med 2000:342:957–65.

3 Weir NU, van Gijn J, Lammie GA, et al . Recur-rent cerebral haemorrhage in a 65 year old manadvanced clinical neurology course, Edin-burgh, 1997. J Neurol Neurosurg Psychiatry1999:66:104–10.

Copper concentration in CSF during the courseof treatment in a 41 year old patient withWilson’s disease. The arrow marks the timewhen the patient started to take his zinc inreduced doses and irregularly.

90

70

80

60

40

50

30

20

0

10

200180140 16012080 100

Month

C o p p e r i n C S F ( µ g / l )

60400 20


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Guillain-Barré, Fisher, and BickerstaV

syndromes: nature versus well

established ideas

As the author of the first ever reportdocumenting central nervous system involve-ment in Miller Fisher syndrome,1 I begpermission to discuss certain aspects of thework of Yuki et al on Guillain-Barré syn-drome and BickerstaV ’s brainstem encephali-tis, an example of which was published in this

Journal .2

Twenty three years ago, I perusedthe literature in search of a diagnosis for achild I had seen in Iran. Eyeing incessantly afew certain guide posts in the neurologicalheavens (Babinski’s response, internuclearophthalmplegia, spasticity) I sailed the lorediligently, arriving at two inescapable conclu-sions: (a) that my patient with a midbrainlesion demonstrated by CT was an instanceof Miller Fisher syndrome, hitherto a variantof Guillain-Barré syndrome; (b) that Bicker-staV ’s brainstem encephalitis and MillerFisher syndrome are one and the same entity.With that perusal behind me, I thought itentirely suYcient to include BickerstaV ’swork in my references and ended the articleby the following statement: It is evident thatour finding, if confirmed, raises questions

regarding pathophysiology of Landry-Guillain-Barré syndrome, of which Fishersyndrome is a limited form. That pivotalobservation has since been amply substanti-ated (see below for an incomplete list of references).

In 1982 the article became the subject of an editorial in the Archives of Neurology inopposition to my position. It was acknowl-edged parenthetically by BickerstaV himself who eventually embraced my second conclu-sion even though he sided with the splitters,considering the entity of a separate disease.The arrival of MRI turned the tide entirely infavour of the lumpers soon after 3, confirmingmy impression of a need for a reappraisalindicated above. Electrophysiological studiespointed to the same conclusion—that is,Miller Fisher syndrom often, if not always, issuperimposed on a Guillain-Barré syndromebackground sometimes so mild requiringcomplex techniques to disclose its presence.4

Frequent shuttling of Yuki et al betweenGuillain-Barré syndrome, BickerstaV ’s brain-stem encephalitis, and Miller Fisher syn-drome when reporting “overlapping” hybridcases means the same thing as well. Manyothers have made similar observations de-scribing an ascending or descending march of the pathology along the brainstem, displayingcorresponding neurological features.5 Thereport of Odaka et al concerning ballism6 in acase of Guillain-Barré syndrome/MillerFisher syndrome is a novel observation, andanother warning to those remaining sceptics

who, while ignoring other guide posts,consider Miller Fisher syndrome strictly aperipheral nervous system disease. But whenYuki et al draw any distinction between Fisherand BickerstaV syndromes they are displayinga lack of historical perspective and paucity of clinical perspicuity which I am rectifyinghere, as this is an important area of neurologywhere the stakes are high and simple logicmust prevail. It is this blurring of traditionalborder between certain maladies aV ecting theperipheral and central nervous system that isthe thrust of what has followed our groundbreaking observation, including the work of Yuki et al (whatever its eventual immunologi-cal import may be).

The role of MRI in the ensuing eventswhich sometimes resembled an eponymouswar deserves a comment. Whereas Ropperand others mistakenly relied on the absenceof a lesion in conventional MRI to refute therole of a central nervous system lesion inMiller Fisher syndrome such instances aremore cogently explained as follows: (a) theexistenceof a pathological diV erence betweena signal producing inflammation and merepresence of a viral infection in the centralnervous system; for example, in a recentreport 30% of clinically proved enterovirus71 related rhombencephalitides had negativeconventional MRI7; (b) the subject of “nor-mal appearing” white matter when in fact it isnot normal may one day loom large here as ithas in the case of multiple sclerosis.

Thus our novel observation of 1979 allevi-ated Fisher’s “certain reluctance to upset wellestablished ideas concerning the disease(Guillian-Barré syndrome)” and removed thestigma of “oddity” and “aberration” from thesyndrome described by the two luminaries,Miller Fisher and BickerstaV , who did notknow of each others’ contributions; nor couldthey have known of the fact that they weredescribing the same clinical entity. And fortwo good reasons—that is, sharing the abovementioned reluctance to upset the well estab-lished ideas concerning Guillain-Barré syn-drome (as admitted by Fisher himself) andpreceding the wonderful age of computerisedneuroimaging by a quarter of a century. Itwas left to the serendipitous observation in a7 year old Persian girl, and its aftermath, forthe facts to be gleaned—as depicted here.

I DERAKHSHAN415 Morris Street, Suite 401, Charleston,West

Virginia 25301, USA

1 Derakhshan I, Lotfi J, Kaufman B. Ophthalmo-plegia, ataxia and hyporeflexia (Fisher syn-drome) with a midbrain lesion demonstratedby CT scanning. Eur Neurol 1979;18:361–6.

2 Yuki N, Massaki O, Hirata K. BickerstaV ’sbrainstem encephalitis subsequent to campylo-bacter jejunoenteritis. J Neurol Neurosurg Psy-

chiatry 2000;68:679–683.3 Fargas A, Roig M, Vazquez E, et al . Brainsteminvolvement in a child with ophthalmoplegia,ataxia, areflexia syndrome. Pediat Neurol 1998;18:73–5.

4 Buchner H, Schuehardt V, Imbert M, et al .Clinical aspects of acute lesions of the brain-stem of inflammatory origin. Fortschr Neurol Psychiatry 1991;59:43–52.

5 Ter Bruggen JP, Van Der Meche FG, de JagerAE, et al . Ophthalmoplegic and lower cranialnerve variants merge into each other and intoclassical Guillain-Barré syndrome. Muscle

Nerve 1998;21:239–42.6 Odaka M, Yuki N, Arai M, et al . Bilateral ballism

in a patient with over lapping Fisher andGuillain-Barré syndromes. J Neurol Neurosurg Psychiatry 1999;67:206–8.

7 Huang CC, Liu CC, Chang YC, e t al .Neurologic complications in children withenterovirus infections. N Engl J Med 1999;341:935–42.

Yuki replies:

Derakhshan wrote “when Yuki et al draw anydistinction between Fisher and BickerstaV syndromes they are displaying a lack of historical perspective”, but we had describedin detail the historical background in theintroduction of our original paper,1 which hedid not cite. In 1951, BickerstaV and Cloake2

described three patients who had ophthalmo-plegia and ataxia as a grave syndrome theycalled “mesencephalitis and rhombencepha-litis”. They speculated that the aetiology of BickerstaV ’s brainstem encephalitis is similarto that of Guillain-Barré syndrome becauseprodromal upper respiratory infection, are-

flexia, and CSF albumino-cytological disso-ciation were detected. In 1956, Fisher3

described three patients who presented withacute ophthalmoplegia, ataxia of the cerebel-lar type, and areflexia as a variant of Guillain-Barré syndrome. One of the three patientsshowed mild drowsiness. In 1957,BickerstaV 4 added five more patients to theoriginal study and named the condition“brain-stem encephalitis”. In 1982, Al-Din et al 5 (BickerstaV being one of the authors)described 18 patients,and considered Bicker-staV ’s brainstem encephalitis to be a distinctclinical entity, not a variant of Guillain-Barrésyndrome on the basis of radiological (threepatients) and pathological (one patient)changes in the brainstem. In 1983, Ropper,6

however, criticised their report. He consid-ered that six of the 18 cases reported by Bick-erstaV ’s group were typical Miller Fisher syn-drome, and that the other 12 representedobscure brainstem lesions without peripheralpolyneuropathy. In 1987, Al-Din7 describedtwo cases in which there was an altered stateof consciousness and motor nerve dysfunc-tion, in addition to the triad of Miller Fisher.He presented a “spectrum hypothesis”, inwhich Guillain-Barré syndrome and the syn-drome of ophthalmoplegia, ataxia, and are-

flexia are at opposite ends of a broadspectrum, although clinically and pathologi-cally distinct. He regarded his reported casesas being in the middle of that spectrum.

Patients showing drowsiness, brisk reflexes,extensor plantar responses, and hemisensorydisturbance, or central nervous system pleo-cytosis usually are considered to have Bicker-staV ’s brainstem encephalitis rather thanMiller Fisher syndrome. Opinions diV er as towhether these two conditions are distinct orrelated because the aetiology had yet to beestablished. While studying serum samplesfrom patients with Miller Fisher syndrome,our attention was brought back to a patientwith BickerstaV ’s brainstem encephalitis pre-viously treated in our hospital. In addition toacute ophthalmoplegia and cerebellar ataxia,

this patient (patient 2 in Yuki et al 1

) hadabnormal plantar responses and becamecomatose. These neurological symptoms,however, disappeared 2 months after onset.At that time, we thought that anti-GQ1bantibody testing could be used to diV erenti-ate between BickerstaV ’s brainstem encepha-litis and Miller Fisher syndrome. Unexpect-edly, the patient had the anti-GQ1b IgGantibody. Therefore, we investigated whethertwo other patients with BickerstaV ’s brain-stem encephalitis had this antibody. All threepatients had high anti-GQ1b IgG antibodytitres, which decreased with their clinicalimprovement.1 As prior infection is frequentin BickerstaV ’s brainstem encephalitis, as inMiller Fisher syndrome and Guillain-Barrésyndrome, an autoimmune mechanism was

suggested in the pathogenesis of BickerstaV

’sbrainstem encephalitis. The finding thatBickerstaV ’s brainstem encephalitis andMiller Fisher syndrome share common au-toantibodies suggested that the autoimmunemechanism is common to both and that theyare not distinct, but closely related condi-tions. BickerstaV and Cloake2 speculated thatthe aetiology of BickerstaV ’s brainstem en-cephalitis is similar to that of Guillain-Barrésyndrome, but the nosological relation be-tween the two had yet to be clarified becauseof the lack of pathological findings inoverlapping cases. We therefore reportednecropsy findings for a patient in whom over-lapping BickerstaV ’s brainstem encephalitis


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and Guillain-Barré syndrome had been diag-nosed clinically.8

EV ective therapy for BickerstaV ’s brain-stem encephalitis has yet to be established.Asshown, BickerstaV ’s brainstem encephalitisand Guillain-Barré syndrome are closelyrelated; therefore, steroids should not be usedto treat these disorders. Instead, the estab-lished treatments—plasmapheresis and intra-venous immunoglobulins (IVIg)— should beused. Recent studies9 10 provide theoreticalevidence that the removal of anti-GQ1b anti-bodies is reasonable and beneficial. Somepatients with BickerstaV ’s brainstem en-cephalitis respond favourably to plasmapher-esis and IVIg.11 12 We recommend that nosteroids, rather IVIg (or plasmapheresis), beused to treat BickerstaV ’s brainstem encepha-litis. Controlled clinical trials are needed toestablish the eYcacy of these procedures astherapy for this disease.

NOBUHIRO YUKIDepartment of Neurology,Dokkyo University School of

Medicine, Kitakobayashi 880, Mibu, Shimotsuga,Tochigi 321–0293, Japan

Correspondence to: Dr N [email protected]

1 Yuki N, Sato S, Tsuji S, et al . An immunologicabnormality common to BickerstaV ’s brainstem encephalitis and Fisher’s syndrome. J

Neurol Sci 1993;118:83–7.2 BickerstaV ER, Cloake PCP. Mesencephalitis

and rhombencephalitis. BMJ 1951;ii:77–81.3 Fisher M. An unusual variant of acute idio-

pathic polyneuritis: syndrome of ophthalmo-plegia,ataxia and areflexia. N Engl J Med 1956;255:57–65.

4 BickerstaV ER. Brain-stem encephalitis: furtherobservations on a grave syndrome with benignprognosis. BMJ 1957;i:1384–7.

5 Al-Din AN, Anderson M, BickerstaV ER, et al Brainstem encephalitis and the syndrome of Miller Fisher: a clinical study. Brain 1982;105:481–5.

6 Ropper AH. The CNS in Guillain-Barrésyndrome. Arch Neurol 1983;40:397–8.

7 Al-Din ASN. The nosological position of theophthalmoplegia, ataxia and areflexiasyndrome: the spectrum hypothesis. Acta Neu-rol Scand 1987;75:287–94.

8 Yuki N, Wakabayashi K, Yamada M, et al . Over-lap of Guillain-Barré syndrome and Bicker-

staV ’s brainstem encephalitis. J Neurol Sci 1997;145:119–21.

9 Plomp JJ, Molenaar PC, O’Hanlon GM, et al.Miller Fisher anti-GQ1b antibodies:-latrotoxin-like eV ects on motor end plates.

Ann Neurol 1999;45:189–99.10 Buchwald B, Weishaupt A, Toyka KV, et al . Pre-

and postsynaptic blockade of neuromusculartransmission by Miller Fisher syndrome IgG atmouse motor nerve terminals. Eur J Neurosci 1998;10:281–90.

11 Yuki N. Successful plasmapheresis in Bicker-staV ’s brain stem encephalitis associated withanti-GQ1b antibody. J Neurol Sci 1995;131:108–10.

12 Yuki N,Odaka M, Hirata K. BickerstaV ’s brain-stem encephalitis subsequent to Campylobacter

jejuni enteritis. J Neurol Neurosurg Psychiatry2000;68:680–1.

Intravenous immunoglobulin causing

reversible posteriorleukoencephalopathy syndrome?

Turner and Wills describe a patient with theMiller Fisher syndrome treated with intra-venous immunoglobulin (IVIg), who devel-oped transient confusion and reversibleblindness.1 The authors state that the bilat-eral occipital lobe changes seen on brain MRIwere secondary to cerebral infarction. Theypostulate that this may have occurred as aresult of hyperviscosity, although at the timeof the event the plasma viscosity was onlymarginally raised at 1.85 cP (normal range1.5—1.72 cP). The images seem to showrelative sparing of the cortex, which would be

rather unusual if the cause was indeed anarterial infarct as would be expected if themechanism was hyperviscosity inducedthromboembolism.2 The authors do not spe-cifically mention that they excluded a cer-ebral venous sinus thrombosis with appropri-ate imaging and although the pattern andclinical history would be slightly unusual, thisis a possibility that needs to be considered.

We suspect, however, that this patientactually experienced the reversible posteriorleukoencephalopathy syndrome (rPLES).This is a syndrome of reversible symptomscomprising any of altered mental function;headaches; visual loss; seizures; andweakness.3 4 The syndrome has been de-scribed with many underlying conditions3 4

and has previously been reported with IVIguse.5 6 The patient reported on1 has many of the clinical and radiological features of rPLES, in particular the MRI changes arepredominantly subcortical and the visionrecovered well. A repeat MRI in this casewould be useful and should show resolutionof the abnormalities seen on T2 weightedimaging with little or no corresponding T1weighted abnormality, showing that the brainhad been oedematous rather than infarcted.

Reversible posterior leukoencephalopathyis an important syndromic diagnosis to makeas it obviates the need for extensive strokerelated investigations and has diV erent impli-cations for prognosis and future manage-ment.

MARK LEWIS

PAUL MADDISONDepartment of Neurology, Leeds General Infirmary,

Great George Street, Leeds LS1 3EX, UK

Correspondence to: Dr M B [email protected]

1 Turner B, Wills AJ. Cerebral infarction compli-cating intravenous immunoglobulin therapy ina patient with Miller Fisher syndrome. J Neurol

Neurosurg Psychiatry 2000;68:790–1.2 Dalakas MC. High-dose intravenous immu-

noglobulin and serum viscosity: risk of precipi-tating thromboembolic events. Neurology 1994;

44:223–6.3 Hinchey J, Chaves C, Appignani B, et al . Areversible posterior leukoencephalopathy syn-drome. N Engl J Med 1996;334:494–500.

4 Lewis MB. Cyclosporin causes reversible poste-rior leukoencephalopathy syndrome. BMJ 1999;319:54.

5 Voltz R, Rosen FV, Yousry T, et al . Reversibleencephalopathy with cerebral vasospasm in aGuillain-Barré syndrome patient treated withintravenous immunoglobulin. Neurology 1996;46:250–1.

6 Mathy I, Gille M, Van Raemdonck F, et al .Neurological complications of intravenous im-munoglobulin (IVIg) therapy: an illustrativecase of acute encephalopathy following IVIgtherapy and a review of the literature. Acta

Neurol Belg 1998;98:347–51.

Turner and Willis reply:

We thank Maddison and Lewis for their

considered comments. They suggest cerebralvenous sinus thrombosis and reversible poste-rior leukoencephalopathy syndrome (rPLES)as two diV erential diagnoses for our reportedcase of IVIg associated with cerebralinfarction.1 Formal magnetic resonancevenography was not performed on the patient;however, the major sinuses were patent onconventional MRI and the clinical picture wasrelatively short lived, making cerebral sinusthrombosis unlikely. The initial MR scan and afollow up scan 11 days later, after clinicalimprovement, demonstrated high signalchanges on T2 and T1 weighted images inboth the cortex and subcortical white matterindicative of irreversible cerebral damage,

most probably infarction. rPLES is a rapidlyevolving neurological condition characterisedby headache, nausea, and vomiting, visual fielddisturbances, altered mental status, decreasedalertness, and seizures.2 The leukoencepha-lopathy syndromes have a heterogeneousaetiology2; reversible multifocal encephalopa-thy has been reported with IVIg,3 but aspointed out by Lewis4 the commonest associ-ation of rPLESs is hypertension. It has beensuggested that in PLES, seizures are thecausative factor and essential in thepathogenesis.5 Our patient had no evidence of epileptic activity or hypertension. Vasogenicoedema is hypothesised as the pathology of rPLES and explains its reversibility2 butclinical improvement is also recognised inthromboembolic pathology. The plasma vis-cosity was not greatly raised in our patient butthere may be other contributing factors forIVIg to cause a thromboembolic phenom-enon. It has beenshown that IVIg preparationscontain anticardiolipin and antiphospholipidantibodies, which may have a role inthromboembolism.6 The images shown in ourpaper1 may not do justice to the radiologicalevidence but along with the raised plasma vis-cosity, the absence of hypertension andseizures we consider cerebral infarction themost likely pathology. Whatever the patho-physiology the lesson remains the same that inunwell patients IVIg should be usedcautiously.

BENJAMIN TURNER ADRIAN J WILLS

Division of Clinical Neurology, University Hospital,Queen’s Medical Centre, Nottingham NG7 2UH, UK

Correspondence to: Dr B [email protected]

1 Turner B, Wills AJ. Cerebral infarction compli-cating intravenous immunoglobulin therapy ina patient with Miller Fisher syndrome. J Neurol

Neurosurg Pyschiatry 2000;68:790–1.2 Ay H, Buonanno FS, Schaefer PW, Le D, et al .

Posterior leukoencephalopathy without severehypertension: utility of diV usion-weightedMRI. Neurology 1998;51:1369–76.

3 Voltz R, Rosen FV, Yousry T, et al . Reversibleencephalopathy with cerebral vasospasm in a

Guillian-Barré syndrome patient treated withintravenous immunoglobulin. Neurology 1996;46:250–1.

4 Lewis MB. Cyclosporin causes reversible poste-rior leukoencephalopathy syndrome. BMJ 1999;319:54.

5 Obeid T, Awada A. Posterior leukoencepha-lopathy without severe hypertension: utility of diV usion-weighted MRI. Neurology 1999;53:1372–3.

6 Krause I, Blank M, Shoenfield Y. Anti-DNAand antiphospholipid antibodies in IVIgpreparations: in vivo study in naïve mice. J ClinImmunol 1998;18:52–60.

Charles Bonnet syndrome: an example

of cortical dissociation syndrome

aV ecting vision?

Although Cole’s article was published some-

time ago,1

it was brought to ourattention onlyrecently during the weekly journal review byone of our senior house oYcers. Myself andmy other neurological colleagues are left withlittle doubt that the symptoms of visualhallucinations experienced by Cole is due tothe Charles Bonnet syndrome (CBS).

This syndrome comprises the triad of visual hallucinations, visual sensory depriva-tion, and preserved cognitive status. Thevisual hallucinations in CBS may persist oneye closure (unlike the visual hallucinationsof hemianopia) and are often complex, vivid,and elaborate consisting of moving andcolourful images. In epidemiological studies,two common factors for CBS were visual


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sensory deprivation typically aV ecting theanterior visual pathway (due to cataract orsenile macular degeneration) and advancedage ( older than 60 years). As the hallucina-tory symptoms in CBS occur with preservedinsight, these are not true but pseudohalluci-nations.

The syndrome occurs as a result of the dis-sociation between visual perception andvisual sensory input in psychologically nor-mal aged people. Functional neuroimaging(fMRI) has shown that the hallucinations of colour, faces, textures, and objects in CBScorrelate with the cerebral activity in the ven-tral extrastriate visual cortex whereas thecontents of hallucinations reflect the func-tional specialisation of this region.2 In ourexperience, carbamazepine has been partiallyeV ective in suppressing the visual pseudohal-lucinations of CBS, presumably because itmight inhibit the increased ventral extrastri-ate neuronal activity in patients with CBSthat persists between the attacks of hallucina-tory symptoms.2

In Cole’s case,1 the occipital infarct in thedominant (left) hemisphere led to the disso-ciation between the visual sensory input (nowlimited to the right striate cortex) and thevisual perception sense of the dominantextrastriate and the visual association cortexspared by the ischaemic event. Collicularvision (“blindsight”) plays no part in thesymptoms of visual hallucination. In the lightof the recent fMRI data, CBS may be consid-ered as a visual dissociation syndrome similarto the cortical dissociation syndromes wellrecognised in the Geschwind model of language function. Cole gives one of the fin-est clinical examples to illustrate this phe-nomenon. Why CBS should occur with visualsensory deprivation exclusively in elderlypeople and not in young people is unknownbut it might reflect the nature of neural plas-ticity in the visual cortex as opposed to theother cortical functions.

We were, however, a little surprised thatCBS did not feature even once in theotherwise erudite discussion of the case

report.1 Did Cole and the reviewers of the Journal not consider this common diagnosticpossibility?

ABHIJIT CHAUDHURIDepartment of Neurology,University of Glasgow, UK

1 Cole M. When the left brain is not right theright brain may be left: report of personalexperience of occipital hemianopia. J Neurol

Neurosurg Psychiatry 1999;67:169–73.2 Ffytche DH, Howard RJ, Brammer MJ, et al .

The anatomy of conscious vision: an fMRIstudy of visual hallucinations. Nat Neurosci 1998;1:738–42.

Corticobasal ganglionic degeneration

and/or frontotemporal dementia?

I read with interest the recent paper byMathuranath et al 1 describing two patientswith the pathology of corticobasal ganglionicdegeneration (CBD), the first presenting withthe syndrome of frontotemporal dementiaand the second with a mixed picturedominated by progressive aphasia. The con-cept that CBD may present with clinical fea-tures distinct from the “perceptuomotor”syndrome widely recognised as “classic” of the disorder is not new. However, untilrecently it had generally been thought thatthese cases represented the minority and thuscould be considered “atypical”. However,knowledge about this disorder has evolvedsince our group and others reported the first

large series. I think that in 2000 it is notappropriate to quote our 1994 book chapter2

stating that “Frank dementia or languagedysfunctions are said to be rare and, if present, are mild, and typically occur late inthe course of the disease,”1 as currentwisdom. Within 2 years of that book chapterourselves and others were reporting alterna-tive presentations for this pathology and mostrecently we have published the clinical-pathological experience of the CanadianBrain Tissue Bank in a paper that waspresumably in press at the time that the paperof Mathuranath et al was being reviewed.3 Inthis study we found that of 13 patients provedpathologically to have CBD, nine presentedwith cognitive or language disturbances, onlyone failed to show dementia during thecourse of the illness and only four were diag-nosed as having CBD in life. Since that time,a 14th patient has come to necropsy whosepresentation was that of primary progressiveaphasia.

There have also been patients reported inthe literature by ourselves and others withalternative neuropathological disorders pre-senting with clinical features that weremistaken for the “classic” (but now it seemsnot the commonest) phenotype of CBDincluding progressive supranuclear palsy,Pick’s disease, motor neuron inclusion bodydementia, Alzheimer’s disease, and familialfrontotemporal dementia due to chromo-some 17 mutations.

In summary, clinical and pathologicalexperience at the turn of the century stronglysupports the conclusions of Mathuranath et al . Clinical phenotypes have not proved to berestricted to specific pathological substraitsand several diV erent clinical phenotypes maybe caused by the same underlying pathology,probably largely dependent on the anatomi-cal distribution of greatest involvement.Where I mainly take issue with the authors isin their belief, which largely justifies theirreport, that a clear distinction between CBDand FTD is “currently accepted”. Thecumulative literature since our 1994 review,

most recently culminating in a monograph ona topic,4 indicates that CBD is no longerthought of as a predominately extrapyramidaldisorder that is distinct and unrelated tofrontotemporal dementia.

ANTHONY E LANGToronto Western Hospital, Toronto,Canada

1 Mathuranath PS, Xuereb JH, Bak T, et al . Cor-ticobasal ganglionic degeneration and/or fron-totemporal dementia? A report of two overlapcases and review of literature. J Neurol

Neurosurg Psychiatry 2000;68:304–12.2 Lang AE, Riley DE, Bergeron C. Cortical-basal

ganglionic degeneration. In: Calne DB, ed. Neurodegenerative diseases. Philadelphia: WBSaunders, 1994:877–94.

3 Grimes DA, Lang AE, Bergeron CB. Dementiaas the most common presentation of cortical-basal ganglionic degeneration. Neurology 1999;

53:1969–74.4 Litran I, Goetz CG, Lang AE. Corticobasal degeneration and related disorders. Philadelphia,PA: Lippincott Williams and Wilkins, 2000.

Diagnostic criteria for corticobasal

degeneration

The study of Mathuranath et al 1 of corticoba-sal degeneration (CBD) and its overlap withfrontotemporal dementia (FTD) contributesinteresting information to a controversial areaof neurodegeneration. Unfortunately it alsointroduces a potentially confusing his-topathological diagnostic error. The authorsfound oligodendroglial inclusions which they

considered to be glial cytoplasmic inclusionsand claimed that these, diagnostic hallmarkof multiple system atrophy, “have beendescribed in other neurodegenerative dis-eases, including CBD”. This is clearly not thecase.

To support their view the authors refer totwo papers2 3 reporting, among other cy-toskeletal abnormalities, tau positive inclu-sions in oligodendroglial cells. A letter,published earlier in this Journal ,4 but notquoted in the current paper,1 hasalso claimedthat glial cytoplasmic inclusions are notexclusive to multiple system atrophy. Theevidence is now overwhelming that they are.What the authors of this1 and the otherpapers2–4 have described are indeed tau posi-tive oligodendroglial inclusions, but they arenot the same as glial cytoplasmic inclusions.5

Oligodendroglial inclusions, chiefly coiledbodies, undoubtedly occur in various neuro-degenerative diseases, including CBD, buttheir morphology and molecular pathologyare diV erent from those of glial cytoplasmicinclusions. Whereas glial cytoplasmic inclu-sions immunostain with -synuclein6 andonly with unphosphorylated tau antibodies,7

the oligodendroglial inclusions seen in CBDand other neurodegenerative diseases are-synuclein negative and give positive reac-tion with both phosphorylated and unphos-phorylated tau antibodies. This basic diV er-ence has been recognised by a newclassification of neurodegenerative disorders:CBD is one of the tauopathies, whereas mul-tiple system atrophy is an -synucleinopathy.Thus glial cytoplasmic inclusions remain themost consistent and reliable diagnostic hall-marks of multiple system atrophy and do notoccur in other neurodegenerative diseases.

P L LANTOSInstitute of Psychiatry, King’s College London,

Department of Neuropathology, London SE5 8AF, UK

1 Mathuranath PS, Xuereb JH, Bak T, et al . Cor-ticobasal ganglionic degeneration and/or fron-totemporal dementia? A report of two overlapcases and review of literature. J Neurol

Neurosurg Psychiatry 2000;68:304–12.2 Wakabayashi K, Oyanagi K, Makifuchi T, et al .Corticobasal degeneration: etiopathologicalsignificance of the cytoskeletal alterations. Acta

Neuropathol 1994;87:545–53.3 Mori H,Nishimura M, Namba Y, et al . Cortico-

basal degeneration: a disease with widespreadappearance of abnormal tau and neurofibril-lary tangles, and its relation to progressivesupranuclear palsy. Acta Neuropathol 1994;88:113–21.

4 Daniel SE, Geddes JF, Revesz T. Glial cytoplas-mic inclusions are not exclusive to multiplesystem atrophy. J Neurol Neurosurg Psychiatry1995;58:262.

5 Papp MI, Kahn JE, Lantos PL. Glial cytoplas-mic inclusions in the CNS of patients withmultiple system atrophy (striatonigral degen-eration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 1989;94:79– 100.

6 Spillantini MG, Crowther RA, Jakes R, et al .Filamentous -synuclein inclusions link multi-ple system atrophy with Parkinson’s diseaseand dementia with Lewy bodies. Neurosci Lett 1998;251:205–8.

7 Cairns NJ, Mackay D, Daniel SE, e t a l .Tau-pathology of oligodendroglial inclusions inmultiple system atrophy, progressive supranu-clear palsy and corticobasal degeneration. Neu-ropathol App Neurobiol 1998;24:145.

Xuereb and Hodges reply

The topic of how to apply the term “glialcytoplasmic inclusions” and their specificityto a particulardisorder is clearly controversialand in a state of evolution. We used glialcytoplasmic inclusions in a non-specific wayto indicate simply the presence of cytoplas-mic inclusions in glial cells. We found these


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inclusions in subcortical oligodendrocytes.Glial inclusions were initially described inmultiple system atrophy by Papp et al in1989;1 their paper brought glial cellularpathology in neurodegenerative disease to theattention of neuropathologists. Cytoplasmicinclusions in glial cells have since beenreported in various neurodegenerative dis-eases. The label “glial cytoplasmic inclu-sions” and the initials “GCIs” used in thegeneral sense cannot, therefore, properly beregarded as pathognomonic of any single dis-ease entity. Indeed, a neuroscientist withoutneuropathological training could conceivablymisdiagnose tissue as coming from a case of multiple system atrophy if that tissue con-tained oligodendroglial cytoplasmic inclu-sions (in silver preparations or ubiquitinimmunohistochemistry). Our paper does not,we would argue, contain a “histopathologicaldiagnostic error” as suggested by Lantos.

On the other hand, Lantos’ criticism thatwe made no mention of recent discoveries of -synuclein involvement in the biology of MSA is justified. In the discussion, we shouldhave emphasised the fact that glial cytoplas-mic inclusions in multiple systems atrophy,and so far only in multiple systems atrophy,are indeed -synuclein-positive and phospho-rylated tau negative, whereas the opposite istrue for the glial cytoplasmic inclusions of CBD and related tauopathies. Lest the futureshould see -synuclein positive glial cytoplas-mic inclusions identified in some otherdisease, it is well to emphasise that thediagnosis of multiple systems atrophy de-pends on the clinical history and distributionpattern of neurodegeneration (which deter-mines the clinical phenotype), and thepresence of -synuclein positive glial cyto-plasmic inclusions is valuable confirmatoryevidence in this context.

We also appreciate Lang’s comments onthe paper and are very pleased that thecumulative Canadian experience mirrors theconclusions of our paper in that languageand/or other cognitive disturbances are a vir-tually universal feature of CBD and in many

cases mayindeed be themode of presentationas highlighted by the recent paper by Grimeset al 2 which appeared after the submission of our manuscript.

JOHN XUEREB JOHN HODGES

MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 2EF, UK

Correspondence to: Professor John Hodges

1 Papp MI, Kahn JE, Lantos PL. Glial cytoplas-mic inclusions in the CNS of patients withmultiple system atrophy (striatonigral degen-eration, olivoponto-cerebellar atrophy, andShy-Dragar syndrome). J Neurol Sci 1989:94:79–100.

2 Grimes DA, Lang AE, Bergeron CB. Dementiaas the most common presentation of cortical-basal ganglionic degeneration. Neurology 1999;53:1969–74.

Assessment and treatment of dizziness

In a recent editorial, Halmagyi and Cremerconsider Menière’s disease in their discussionof recurrent spontaneous vertigo.1 Menière’sdisease is a diagnosis of exclusion. Many con-ditions may present with the triad of hearingloss, vertigo, and tinnitus, most importantlyvestibular schwannomas.2 Gadolinium en-hanced MRI imaging is the current goldstandard for diagnosing vestibular schwan-noma and is mandatory before giving some-body the diagnosis of Menière’s disease. The

Committee on Hearing and Equilibrium of the American Academy of Otolaryngology— Head and Neck Surgery have set outguidelines for the diagnosis and evaluation of therapy in Menière’s disease.3

Audiovestibular testing can be useful inMenière’s disease. Caloric testing has poorsensitivity and specificity in diagnosing thedisease. Electrocochleography and glyceroldehydration testing can be useful in theearlier stages of the disease before the hearingfunction is irreversibly and severely lost. InMenière’s disease,the most common findingson electrocochleography are an increasedsummating potential to action potential ratio,a widened summating potential/action poten-tial complex, and a disturbed cochlear micro-phonic potential.4

For medical treatment, dietary advice withstrict sodium restriction is useful. However,betahistine probably helps more patients withMenière’s disease than any other drugs.Labyrinthine sedatives are also helpful inpatients who have severe attacks of vertigo.5

Surgical treatment of Menière’s disease treatsonly the vertigo. A wide range of operationshave been described, from grommet insertionto vestibular nerve section, all of which havehad a similar degree of success. These areparticularly diYcult to compare due to thehuge variations in the natural history of thedisease.

Assessment and treatment of patients withbalance disturbance covers many specialties,who all approach the problem from slightlydiV erent angles with diV erent perspectives. Itis important to liase closely with colleagues inassociated specialties to optimise the diagno-sis and treatment of these patients.

A P COATESWORTHDepartment of Otolaryngology,Leeds General

Infirmary,Great George Street,Leeds LS1 3EX,UK

1 Halmagyi GM, Cremer PD. Assessment andtreatment of dizziness. J Neurol Neurosurg Psychiatry 2000;68:129–36.

2 Ramsden RT. Vestibular schwannoma. In: Scott-Brown’s otolaryngology 6th ed . Oxford:Butterworth-Heinemann 1997:3/21/1–38.

3 Committee on Hearing and Equilibrium.Guidelines for the diagnosis and evaluation of therapy in Menière’s disease. Otolaryngol Head

Neck Surg 1995;113:181–5.4 Gibson WPR, MoV at DA, Ramsden RT.

Clinical electrocochleography in the diagnosisand management of Menière’s disorder. Audi-ology 1977;16:389–401.

5 Brookes GB. The pharmacological treatment of Menière’s disease. Clin Otolaryngol 1996;21:3– 11.

Halmagyi and Cremer reply:

One cannot help but feel a certain sense of nostalgia reading Coatesworth’s textbookdescription of Menière’s disease: if only thereal world was like that. We deal with hiscomments in order.

Menière’s disease is a diagnosis of exclusion —It

is diY

cult to conceive what needs to beexcluded in a patient who has repeated devas-tating attacks of acute spontaneous vertigolasting several hours as well as unilateral tinni-tus, aural fullness, and fluctuatinghearingloss.When the audiogram shows a unilateral lowfrequency sensorineural hearing loss, thecaloric test shows a canal paresis and the elec-trocochleogram shows a pathologically largesummating potential to action potential ratio1

the patient has Menière’s disease. Menière’sdisease is a clinical diagnosis supported bylaboratory testing. It is no more a diagnosis of exclusion than is multiple sclerosis.

The vestibular schwannoma story —This is adiYcult one. Maybe the answer is that if

someone else is paying and the lawyers arewatching anyone with any unilateral balanceor hearing problem should have a gadoliniumenhanced MRI in case they are harbouringwhatmight eventually become a symptomaticintracanalicular vestibular schwannoma(“acoustic neuroma”). If the patient actuallydoes have one,then the problem becomes notso much the dizziness but what to do aboutthe “tumour”. Vestibular schwannomas can,very rarely, present with one, at the most two

attacks of acute spontaneous vertigo,

2

just asthey can, rarely, present as sudden hearingloss.2 We see about 2500 new patients eachyear in our balance disorders clinic and in thepast 15 years we have seen three patients withacute spontaneous vertigo who had smallvestibular schwannomas.

Caloric testing has poor sensitivity and specifi-

city in diagnosing Menière’s disease — In part itdepends who does it. Technical standards forcaloric testing are in general not as rigorouslyenforced as those for audiological testing.Some factors that can have a profoundinfluence on the quality of the results include:(a) method of recording—DC electro-oculography versus infrared and video meth-ods;(b) method of removing fixation—eye clo-sure versus darkness; (c) method or

irrigation—water versus air.3

Caloric testing(or “ENG”) is no more specific forany diseasethan is EMG.It shows the site of lesion not thenature of the lesion. When one is confident inthe technical standards of the caloric testingthe most helpful finding in the diagnosis of Menière’s disease is a fluctuating unilateralvestibular loss—the vestibular equivalent of the classic fluctuating hearing loss.

Electrocochleography (ECOG) —Again, itdepends on who does it. An ECOG withextratympanic recording of the responses toclicks alone is generally useless or worse, mis-leading. A transtympanic recording of theresponses to tone bursts can disclose, un-equivocally, the presence of endolymphatichydrops, the pathophysiological basis of Menière’s disease.4 The test is, as Coates-

worth notes, most useful in the early stagesbefore a severe fixed hearing loss due to lossof hair cells.

Surgery for Menière’s disease —Vestibularnerve section stops the vertigo attackswithout worsening the hearing but mightcause chronic vestibular insuYciency.5 Intra-tympanic gentamicin is a lotsimpler andsaferand might be just as good at stopping the ver-tigo but can worsen the hearing.6 Endolym-phatic sac surgery ? The controversy stillrages.7 8

We certainly agree on the need forcooperation between specialties in the man-agement of patients with dizziness. Neurolo-gists needs to work with otolaryngologistswho have expertise and interest in otology.The neurologists of Leeds should know how

lucky they are to have one.G MICHAEL HALMAGYI

PHILLIP D CREMER Royal Prince Alfred Hospital, Sydney, Australia

Correspondence to: Dr G Michael Halmagyi

1 Sass K Sensitivity and specificity of transtym-panic electrocochleography in Menierè’s dis-ease. Acta Otolaryngol (Stockh) 1998;118:150–6.

2 Morrison GA, Sterkers JM. Unusual presenta-tions of acoustic tumor. Clin Otolaryngol 1996;21:80–3.

3 Halmagyi GM, Yavor RA, McGarvie LM. Testsof vestibular function. In: Jerger J, Alford B,

Jenkins H, eds. Electrophysiologic evaluation inotolaryngology. Basel, Karger, 1997;53:132–54.


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4 Gibson WPR, Arenberg IK. Pathophysiologictheories in the etiology of Menierè’s disease.Otolaryngol Clin North Am 1997;30:961–8.

5 Reid CB, Eisenberg R,Halmagyi GM,et al .Theoutcome of vestibular nerve section for intrac-table vertigo:the patients’ point of view.Laryn-

goscope 1996;106:1553–6.6 Murofushi T, Halmagyi GM, Yavor RA. Intra-

tympanic gentamicin in Menierè’s disease:results of therapy. Am J Otol 1997;18:52–7.

7 Pensak ML, Friedman RA. The role of endol-ymphatic shunt surgery in the managed careear. Am J Otol 1998;19:337–40.

8 Thomsen J, Bonding P, Becker B, et al . Thenon-specific eV ect of endolymphatic sac sur-gery in treatment of Menierè’s disease: aprospective, randomized controlled study com-paring the “classic” endolymphatic sac surgerywith the insertion of a ventilating tube in thetympanic membrane. Acta Otolaryngol 1998;118:769–73.

BOOK REVIEWS

Cranial base surgery. Edited by JAMES T

ROBERTSON, HUGH B COAKHAM, and J ON H

ROBERTSON. (Pp 688, £150.00). London:

Churchill Livingstone,2000. ISBN0-443-056854.

Cranial Base Surgery is a multiauthored text-book with internationally recognised con-tributors from Europe and the United Statesof America. The stated aim of the editors is tocollate the experience of skull base surgeonsto provide an account of the contemporarymanagement of skull base lesions includingsurgical techniques and outcome data. How-ever, because of the rarity of some of thelesions, the authors admit that long term dataon their outcomes are not yet available, whichprecludes definitive statements about the bestmanagement plans.

The book is divided into four sectionsdealing initially with presentation and diag-

nosis and sequentially with the surgicalapproaches, pathological conditions and fi-nally with adjuvant therapy for cranial basetumours.

The section on general considerations con-centrates on neuroimaging, interventionalneuroradiology, neurophysiological monitor-ing, and neuroanaesthesia. The chapter oncritical surgical anatomy is excellent and cer-tainly for this reviewer provided a useful revi-sion exercise.

The chapters dealing with surgical ap-proaches to the cranial base will be most use-ful to those who are in training rather thanproviding any new information to those whoalready have an established practice, althoughit does provide a logical overview of thediV erent approaches.

The mark of a good operative text iswhether, when one has read and digested it,one would have the confidence to undertakethe procedure. For experienced surgeons theanswer would be yes but for those in trainingthe text is not supported by the quality of theillustrations. These are largely black andwhite and have been executed by diV erentartists, which gives them a non-uniformappearance. The intraoperative photographsare unsatisfactory; for example, a picture of ajuvenile nasopharyngeal angiofibroma wasunrecognisable.

The third section comprises 13 chaptersrelating to the individual surgical pathologyof tumours and vascular lesions. In these

chapters there is repetition of the materialalluded to in the surgical approaches section.Despite this the transglabellar subfrontalapproach was not described either in the surgical approaches section or in the chapter onolfactory groove meningiomas.

The chapters on surgical pathology wouldhave benefited from having standard sub-headings which would have simplified accessto specific information such as that relating tooutcome data. The excellent chapter by

Jennetta and Resnick on microvascular de-compression would have provided an idealtemplate for this, and the intraoperativecolour photographs in the chapter on themicrosurgical treatment of trigeminal neural-gia demonstrates what might have beenachieved in the other chapters where suchquality photographs were absent. The man-agement algorithms at the end of each chap-ter of surgical pathology provide a usefuladjunct although I note no mention of stere-otactic radiosurgery was made in relation tothe treatment of trigeminal neuralgia.

Much work and no little suV ering hascharacterised the evolution of the surgicalapproaches to the skull base. There can be nodoubt that on occasion these formidable sur-gical procedures may have led to as theauthors state “unnecessary significant mor-bidity“. It is encumbent upon us to embraceadvances which might in the future make oursurgical approaches redundant. It is to behoped that over the next 10-20 years resultsof carefully undertaken studies comparingoutcome and morbidity between surgery andadjuvant therapies will allow us to makedefinitive decisions as to how best managepatients with skull base tumours. It is to behoped that future editions of this text (eitheras a paper text or CD Rom) will reflect theseresults.

The last chapter is about primary bonedisease of the skull base. It is not clear why itis included in the section relating to adjuvanttherapy and would have been more appropri-ate in the section on surgical pathologies.

The book itself is attractive to look at and

handle with good quality paper and font.In summary, this is an excellent text book

review of the state of the art of cranial basesurgery, largely fulfillingthe statedaims of theeditors. I would hope that a future editionwould include improved illustrations andmore editing of the operative procedures.

I would certainly recommend this book tothose in training with an interest in skull basesurgery and to those already established whowish to have a definitive textbook to delveinto occasionally.

NIGEL MENDOZA

EMG Waveforms: Video Companion to

Electromyography and Neuromuscular

Disorders. Edited by DAVID C PRESTON andBARBARA E SHAPIRO. (Pp 56, £55.00).Published by Butterworth Heinemann,Oxford, 2000. ISBN 0750672293.

This is a well constructed video with plentyof examples of EMG phenomena of interest tothe trainee clinical neurophysiologist. Somecommon and unusual examples are includedwhich provide an opportunity to recognisethem, particularly when they can sometimesbe diYcult to capture and demonstrate in theclinic.

There are only a few minor areas of concern. It would be helpful to know some of the clinical background behind the various

cases presented, which would probably helpin the understanding and interpretation of the various abnormalities. On occasion, theEMG pictures seem to be slightlyout of focusand future availability in a digital formatmight be more convenient. The accompany-ing booklet is essential (related to theauthors’ textbook, reviewed in an earlier edi-tion of this Journal ), and is required readingthroughout the video. An auditory commen-tary may have been easier to follow. Forfuture editions, a quiz type session at the endof the video might also be a useful trainingexercise.

Despite these reservations, this is a goodtraining video and I recommend it.

SIMON BONIFACE

Neural transplantation: an introduction.By WILLIAM J FREED. (Pp 561, £39.95).Published by MIT Press, London, 2000.ISBN 0 262 06208 9.

This book by Bill Freed summarises the fieldof neural transplantation and as might beexpected from this author the approach issomewhat diV erent. Bill Freed was one of theoriginal scientists involved with the early pio-

neering work on neural transplants especiallyin the experimental exploration of adrenalmedullary transplants in Parkinson’s disease.He is not to be confused with the controver-sial neurosurgeon Curt Freed, the principalinvestigator of the recent double blindedembryonic nigral grafts trial in Parkinson’sdisease. This book is written by one who sawthe field develop out of its experimentalorigins into the clinical domain, and as suchshould be capable of providing the readerwith a balanced rationale to neural transplan-tation. Unfortunately, it fails to do thisbecause it often rambles oV into quasiphilo-sophical topics, which is a shame as it under-mines much that could be gleaned from thistome.

The book begins with a preface that sets

the tone of the rest of the book, concludingwith a rather odd quotation from The jigsawman by Larry Niven. The book then leadsthrough a series of introductory chapterswhich includes a list of conditions that maybe suitable for transplantation. This listrather extraordinarily contains schizophreniabut other more sensible candidates such asmotor neuron disease or cerebellar degenera-tions do not make an appearance at all.Immersed in this early section of the book ischapter 7 which discusses neural transplantsin terms of changes in personality. Althoughthis is of interest it is clearly out of place in anintroductory book such as this, not leastbecause it confuses in the readers mind thenotion of selective grafts for neurodegenera-tive conditions with the ludicrous head trans-

plants that some have advocated. Thus thebook has the potential to lead the uninitiatedto think that the ultimate goal of neuraltransplantation is brain replacement ratherthan brain repair. Thebook thereafter returnsto a more logical and better balancedapproach but sadly detours at the end intodangerous waters once again with a mis-judged final concluding chapter.

In summary, the book contains much of interest butpresents it in a fashion that makesit diYcult to recommend. So for those want-ing an introduction to the subject of neuralgrafting this is not the book to read, becauseof its eclectic approach. To those familiarwith the field, it represents an interesting


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diversion, but is deeply irritating in parts andcreates a sense of confusion as to where BillFreed thinks the field is going—a situation atvariance with those actively involved in thefield.

ROGER BARKER

Current progress in the understanding

of secondary brain damage from

trauma and ischaemia. Edited by A

BAETHMANN et al . (Pp 116; £46). Publishedby Springer Verlag, Wien, 1999. ISBN 3 21183313 7.

The editors of this short book have drawntogether the Proceedings of the 6th International Symposium on Mechanisms of Secondary BrainDamage including Novel Developments, whichwas held in Mauls/Sterzing, Italy in February1998. It takes the form of a supplement for Acta Neurochirurgica, which traditionally con-tributed significantly to the subject.

The topics covered are variable, written bymultiple authors from diV erent nations. Theyaddress both the experimental and clinicalaspects of brain injury in ischaemia, touchingon modern concepts. They are organisedunder the headings of molecular and cellular

mechanisms, cerebral ischaemia, and remain-ing problems in severe head injury. Eachchapter provides comprehensive up to datereferences.

Although clinical issues aretouched on,thegeneral theme of the book is promoting novelideas in experimental brain ischaemia andtheir potential extrapolation into the clinicalfield. As such, it is of great interest to thoseinvolved in the experimentation of cerebraltrauma and ischaemia, and to those clinicianswith a very high subspecialty interest in thisarena. Although most of the chapters are of high calibre, those addressing mechanisms of secondary mitochondrial failure, molecularsignals for glial activation, gene expression,and recovery from cerebral ischaemia andmodellingof the ischaemic penumbra I found

particularly informative.PJ KIRKPATRICK

Neuroimaging: Clinical and Physical

Principles. Edited by RA ZIMMERMAN, WA

GIBBY, and RF CARMODY. (Pp 1642, £124.00).Published by Springer-Verlag, New York,2000. ISBN 0 387 94963 1.

This large single volume textbook has almost30 contributors. Many chapters are writtenby more than one person, but one of the edi-tors has personally contributed almost a thirdof the text, including the first 11 chapters on“physical principles”: computed tomography(60 pages) and magnetic resonance imaging

(350 pages). The remainder of the book isdivided into four sections. “Clinical princi-ples: normal anatomy and variants” consistsof one chapter on “normal variations of theskull and its contents”, with 95 figures, butnot a single skull radiograph or any referenceto anomalies of the cerebral vasculature.There are 15 on “brain and skull”, ratherheavily weighted towards children, which isperhaps not surprising given that the firsteditor is one of America’s foremost paediatricneuroradiologists. The five chapters makingup the “orbits, paranasal sinuses, and skullbase”are distinctly disappointing, at least twoprobably best skipped over.The secondof theseven chapters on “spine” is a rather superfi-

cial review of myelography, which to a Euro-pean also seems anachronistic (although I amassured that many myelograms are stillcarried out in the United States for medicole-gal reasons, which seems perverse!). Theauthor claims that “in older patients, whogenerally have considerable cervical spondy-losis and thoracic kyphosis, the C1–2 injec-tion technique is preferred”. Leaving asidethe agist slur on elderly Americans, manyexperienced neuroradiologists would firmlyreject this.

Curiously, there are no correspondingchapters on sonography or cerebral or spinalangiography, although chapter 23, “Interven-tional neuroradiology”, is written so as tosuggest that the authors thought the lattertopics would be covered elsewhere. Bizarrely,however, the chapter on “haemorrhage” inthe principles of MRI section, oV ers “tips” onangiographic diagnosis of intracranial haem-orrhage! Chapter division is rather idiosyn-cratic throughout, so that, for example,inflammatory disease of the spinal cord isdealt with under “brain and skull”, whereasinflammatory spinal column disease comes500 pages later. There is significant repeti-tion, two contributors illustrating a metopicsuture, and Alzheimer’s disease crops up inabout half a dozen diV erent places.

In the 1980s, postgraduate students oftensought a recommendation for a single volumeneuroradiology textbook. Now there is ahandful to choose from, and it is diYcult topick a winner: most, like this one, have meritsand failings, some to a greater degree. Thechoice might be guided by the space left onthat quasitheoretical “departmental shelf”; at£124 for a very well produced radiologybook, “Neuroimaging” is certainly not un-duly expensive. Another text, recently pub-lished with the same title,was more obviouslyoriented towards that no man’s land betweenneuroradiology and neurology which inEurope is usually referred to as “neuroimag-ing”. This one is very definitely a neuroradi-ology text: “Neuroimaging and nuclear medi-cine” is relegated (appropriately, some would

say) to the 13 page appendix B, whichincludes three and a half pages of text on“clinical applications”.

The text is moderately well written,accepting that not all the authors haveEnglish as their first language, but the indexcould have been better. The illustrations aregenerally of very good quality (although thereare some appalling graphics in chapter 14,and the legends of some figures in chapter 19do not say what conditions they show). Myfavourite thing is figure 11.95. The caption,which I quote in its entirety, similarly doesnot draw attention to the specific radiologicalfeatures, and one can only wonder whetherthe author is settling some heartfelt score:“This is a coronal CT scan of a thick-skinned73-year-old retired businessman”!

I S MOSELY

Pediatric Neurosurgery. Edited by M

CHOUX, C DI ROCCO, A D HOCKLEY, et al . (Pp875, £170.00). Published by ChurchillLivingstone, London, 1999. ISBN 0 44305630 7.

In a suitably resourced healthcare system it isno longer acceptable for children to receiveneurosurgical care from a surgeon who onlyoccasionally dabbles with “small adults”.Those who provide paediatric neurosurgicalcare must understand the diV erences be-

tween the developing nervous system and thedegenerating one that our adult colleagueshave to deal with. Likewise it is no longerappropriate to add the odd chapter onchildren onto a predominantly adult text-book. This multiauthor textbook is thereforewelcome and should be on the bookshelf of any department where paediatric neurosur-gery is carried out.

It is in competition with two othermultiauthor textbooks, all unimaginativelycalled “Pediatric Neurosurgery”. For the nextedition I wouldadvise thepublishers to createsome distance from the other two by spellingthe title properly, for the main diV erencebetween this book and the others is that it ispredominantly European in its authorshipand style, whereas the others are almostexclusively North American. All three booksare comprehensive and well written byleaders in the field and the diV erencesbetween them are predominantly of style.The North American books I find a little toobusinesslike, being the type of books you justwant to look things up in. This Europeanbook conveys the same information in a morerelaxed style which I find informative,entertaining, and more readable than thecompetition.

I think that an institution performing pae-diatric neurosurgery should have all threebooks in the department. An individual prac-tising or planning a career in paediatric neu-rosurgery should have at least one, the choicebeing dependent on which style suits thatperson. Before being asked to review this vol-ume I had already purchased all three TheAmerican books I keep in my oYce where Ican easily consult them for the odd fact orreference. This book stays on our children’sward where its style encourages all staV topick it up and enjoyably read about the con-ditions they are treating.

PETER RICHARDS

Multiple Sclerosis: the Questions You

Have—the Answers You Need. Edited byR C KALB. (Pp 614, US$39.95). Published byDemos Medical, New York, 2000. ISBN 1– 888799–43–9.

People with multiple sclerosis feel deprived of information about their condition, a feelingwhich is most acute just after formal diagno-sis and early in the course of the disease. Thisnew edition of the American question andanswer book is published within weeks of asimilar, but shorter, publication from Robin-son et al in the United Kingdom.1

The book, edited by a clinical psychologist,contains chapters written by specialists,including neurologists, physiotherapists andoccupational therapists, speech pathologists,

psychologists, nurses, financial advisers, em-ployment experts, and lawyers, some of whom are themselves people with multiplesclerosis. It uses team work to formulate andanswer hundreds of potential questions andin an information oriented society in which itis often hard to know which information totrust it promises to be ‘trustworthy, factualand honest’.

The problem with such texts is that theindividual questions never seem preciselycorrect for the individual patient and, despitethe chapter headings, it is diYcult to findany specific question; questions on treat-ment,for example, appear in the chapterson neurology, treatment, physical therapy,


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and sexuality. None the less, it providesreasonable, comprehensive, and factual an-swers and does not show the bias of manycurrent internet information services. It isNorth American in style and content and theuseful appendix on resources has littlerelevance outside the continental UnitedStates. It provides information for peoplewith multiple sclerosis and would be useful ina multiple sclerosis resource centre in theUnited Kingdom provided that the peoplewith multiple sclerosis who use it rememberthe advice from Dr Schapiro in the forwardthat “it is no substitute for talking with yourhealth professional”.

DAVID BATES

1 Robinson I, et al . MS at your fingertips. London:Class Publishers, 2000.

Hormone Therapy and the Brain: a

Clinical Perspective on the Role of

Oestrogen. By V W HENDERSON. (Pp 112,£28.00). Published by Parthenon PublishingGroup, Carnforth, 2000. ISBN 1–85070– 078–8.

The role of sex steroids in neurological

disease is a topic of importance in our agingpopulation and very worthy of discussion.This book is set out in chapters focusing ondiV erent individual subspecialties, includingdementia, vascular disease, and epilepsy, withan initial backdrop of basic science followedby a discussion of clinical studies and obser-vations. The chapters are concise and wellillustrated with pathological material, photo-graphs, and bright flow diagrams. Theyprovide an informative introduction to thefield, but lack depth of discussion in clinicalapplications.

Study findings are often summarised inhistogram format, but lack confidence inter-

vals, thus limiting the visual interpretation of data. Studies summarised in figures andtables are numerically referenced and thus donot instantly draw the reader to namedresearch groups whose material would be of further interest.

As a clinician the discussion of dementiacaught my interest and the argument fordetailed controlled trials of oestrogen inAlzheimer’s disease seemed most compelling,perhaps reflecting the author’s clear interest

in this field.Overall, this is a relatively light read whichserves as an excellent introduction to thefield, easily accessible to medical studentsand junior neuroscientists. I think that itwould be a worthy addition to the universitylibrary, but the text lacks suYcient meatinessto inspire purchase by the individual neurolo-gist.

KIRSTY HARKNESS

Headache and Facial Pain. By F MONGINI.(Pp 292, DEM 228.00). Published by Thieme,

Stuttgart, 1999. ISBN 3 13 116541 3.

There exists a wide discrepancy between the

excitement of recent advances in the patho-physiology of headache, including the neu-rovascular hypothesis of migraine, serotiner-gic receptor pharmacology,and knowledge of the involvement of brainstem structures inhead pain, and the often low level of enthusi-asm for headache management in the UnitedKingdom. In this volume Mongini presents apersonal view of headache and facial painaetiology and management which comple-ments other researchers in the field.

The first section concentrates on theimportance of facial, cervical, and mastica-tory muscles in the aetiology of headache

with some excellent anatomical illustrations.Reference is also made to serotinergicmechanisms in migraine but this could havebeen expanded to include a more currentview of the neurovascular hypothesis of migraine and also a discussion of calciumchannelopathies in the pathogenesis of mi-graine.

The second clinical section describes indetail the examination of the muscles of mas-tication including palpation of trigger points

and recognition of bite abnormalities. Thissection would have benefited from more dis-cussion of the features of secondary head-aches, altered intacranial pressure syn-dromes, the importance of vascular riskfactors in migraine assessment, and unusualvariants of migraine such as familial hemiple-gic migraine. Mongini includes many clearphotographs of patients with abnormalities of masticatory muscles and tension relatedsymptoms to illustrate his points.

The chapters on management of headacheare based around case discussions, with anemphasis on physical therapy for the cervicaland masticatory muscles and on treatment of comorbidity of depression as being para-mount to successful therapy. Whereas therecognition of concurrent depression cannot

be over emphasised in its importance it wouldhave been useful to include a comments onthe stepwise approach to migraine therapyand a guide to the use of triptans. Perhaps themost obvious omission in this section is a dis-cussion of chronic daily headaches with anal-gesic misuse, probably the most commonproblem seen in headache clinics.

This book should be used as an adjunct toother headache texts on themarket to give thereader an insight into a management strategyfor those patients with challenging andunusual headache problems.

N J GIFFIN



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