dissociable - bmjjournalofneurology, neurosurgery, andpsychiatry 1986;49:1354-1360...

Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:1354-1360

Decline of cognition in multiple sclerosis: dissociabledeficitsA JENNEKENS-SCHINKEL, E A C M SANDERS

From the Department of Neurology, University Hospital, Leyden, The Netherlands

SUMMARY Three female patients (ages 32, 37 and 27 years) developed progressive deficits of cogni-tion in stages of multiple sclerosis in which physical disability ratings were low. Neuropsychologicalexamination revealed severe cognitive impairments in the first two patients. Cognitive functioningwas essentially intact in the third patient, although her work pace was significantly slowed. CTscanning of the brain showed cortical atrophy as well as white matter lesions in patients 1 and 2, andmultiple lesions and oedema of predominantly white matter in patient 3. The differences of cognitivedysfunction between the third and the first two patients may be related to involvement of differentanatomical structures.

Mental symptoms of multiple sclerosis have beendescribed repeatedly since the earliest clinicalreports,' without having led to generally acceptedviews about the kind and the extent of the cognitiveimpairment2-" and the pathopsychological mech-anism.349' In addition, the relationship to otherfunctional disturbances is as yet unclear; someauthors have assumed that the severity of mentalchanges is related to the extent of motorimpairment,2 4 which is denied by others.6 Demen-tia is said to occur predominantly in relatively latestages of the disease.9 12 However, neuropsycho-logical testing may reveal cognitive impairment inpatients who are thought to have intact mentation onroutine clinical examination.8 13-15 The neuro-pathological substrate of neuropsychologicallydocumented cognitive deterioration in multiplesclerosis has as yet been investigated by only a fewauthors.'4 16Two cases with marked dementia concurrent with,

and in one patient even preceding, the neurologicalsigns and symptoms of cerebral multiple sclerosis arepresented. Both cases suffered from chronicallyprogressive multiple sclerosis. A third patient isdescribed whose CT scan indicated fulminant cere-bral multiple sclerosis but who, surprisingly, hadnear-normal mentation on bedside clinical testing. All

Address for reprint requests: A Jennekens-Schinkel, Departmentof Neuropsychology, University Hospital, 2333 AA Leyden, TheNetherlands.

Received 8 November 1985 and in revised form 19 February 1986.Accepted 4 April 1986

three patients were neuropsychologically assessed inorder to quantify and, if possible, define the patternsof cognitive deterioration.The combination of neuropsychological and CT

scan findings suggests that in the latter patient slow-ing of cognitive processing was related to whitematter dysfunction, whereas in the first two patientsdisturbed cognition was related to both cortical atro-phy and white matter involvement. This suggests thatmultiple sclerosis may affect cognition in at least twoways.

Case reports

Case 1An unmarried, right handed woman, aged 20 years, was ingood health until the first half of 1972. She engaged activelyin several sports and frequently won prizes in championshipmatches. In 1972, her fiance (later her husband) noticed thatshe occasionally reacted strangely and became almost dullduring social events. Surprisingly, she failed an examinationas a sports' teacher in 1974, and her achievements in activesports diminished. She married in 1974. In August of thatyear she complained of sudden visual loss in the right eye,diagnosed by an ophthalmologist as acute optic neuritis.Visual acuity recovered within two weeks. She complainedof double vision during a three week period in 1977. Herwork record (automatisation of a dairy factory adminis-tration) deteriorated; with increasing frequency she forgottasks or performed them deficiently so that, by 1980, she hadto stop working. During the following 4 years the cognitivedeterioration was rapidly progressive and she became unableto run her household. From 1982 it was hazardous to leaveher unattended at home and in 1983 she (at age 31 years) wasadmitted to a nursing home for severely demented people.Lumbar CSF in 1977 revealed oligoclonal IgG bands,

1354

guest. Protected by copyright.

on Septem

ber 4, 2021 byhttp://jnnp.bm

j.com/

J Neurol N

eurosurg Psychiatry: first published as 10.1136/jnnp.49.12.1354 on 1 D

ecember 1986. D

ownloaded from

http://jnnp.bmj.com/

Decline of cognition in multiple sclerosis: dissociable deficits

0D 0D

13 Demyelination

Ventricular enlargement +cortical atrophy

Fig 1 Case ! (age 32 yr) (a) schematic representation of (b); (b) CT scan showingage-inappropriate enlargement ofventricles, (periventricular) hypodense lesions and severecortical atrophy; (c) copy ofthree-dimensional design showing loss ofstructure and iteration ofline segments.

indicative of multiple sclerosis. On re-examination in June1984 she was euphoric, disoriented in place and time, andunable to give reliable personal information because ofchildish and dependent behaviour. The temporal part of theright optic disc was pale. A fine nystagmus was presenton horizontal gaze to the right. The finger-nose test wasmoderately ataxic on the left side.At neuropsychological assessment the patient was

euphoric and she used indecent words. She was docilelycooperative. Her concentration was poor and she showedextreme bradyphrenia. Intelligence testing (Wechsler"7Adult Intelligence Scale) revealed a Full Scale IntelligenceQuotient (FSIQ) of 57, far below her estimated premorbidlevel of 100-110. Verbal IQ (VIQ) was 65 and performanceIQ (PIQ) was 56. She performed all subtests extremelypoorly (weighted scores 0-3). She managed only the simplestitems from the Stutsman"8 Intelligence test for preschoolchildren. Registration of aurally presented digits and ofvisu-ally presented nonverbal material was limited to four items(normal 7 items). She was unable to keep track of sequencesexcept automatised ones such as counting from I to 20 orsaying the alphabet. Reproduction of simple narratives waspoor and perseverative, both with aural and visualpresentation. Line drawings were reproduced fragmentarilyand distortedly. Of ten word pairs only four easy pairs werelearnt in three trials. The Memory Quotient (MQ) on theWechsler"9 Memory Scale was 54 (estimated premorbid MQ

110). Arithmetic skills had disintegrated, only addition andsubtraction of digits below 10 were correct. On dictatednumbers she iterated elements, showing a remote intuitionof number structure. Language comprehension and oral lan-guage production were childish, without signs of specific lan-guage disorders. Picture naming was, however, defectivebecause of erroneous interpretation and a slight anomia. Inword fluency tasks the patient produced few and mainly sca-brous words. Reading of letters and simple words was intactbut in sentence reading she made many mistakes and losthold of the task. Writing to dictation and copying weredefective. Speech melody was scanning. The copies of two-and three-dimensional designs showed remarkably goodconnections of line segments and quite skilful stroke,reflecting only minor motor involvement of the arms. Lossof structure and iteration of segments (fig lc) were featuresof constructional disability per se. Recognition of objects,images, sounds and body-parts was intact. Left-right dis-crimination errors and difficulty in finger naming occurredonly when commands were complex. On verbal request shesucceeded only in demonstrating object use if concreteobjects were at hand. Reaction times were long and choicereactions were erroneous. In summary, she was a woman inwhom a range ofcognitive abilities had deteriorated severelyand whose personality had regressed.

Laboratory testing was repeated in 1984. Blood count,serum urea, electrolytes, liver functions, calcium and phos-

1355


on Septem


j.com/

J Neurol N


ecember 1986. D

ownloaded from


Jennekens-Schinkel, Sanders

Fig 2 Case 2 (age 37 yr) (a) schematic representation of (b); (b) CT scan showingage-inappropriate enlargement of ventricles and signs ofcortical atrophy; (c) copy of three-dimensional design showing severe loss ofstructure.

phate were normal. The measles antibody titre in the serumwas negative. The CSF of the patient contained 11cells/mm3, with lymphocytes and atypical plasma cells. TheIgG index was elevated' 2 and isoelectric focusing revealed anumber of oligoclonal bands, indicating intrathecal IgG syn-thesis. A CT scan showed severe cortical atrophy and ven-tricular enlargement with white matter atrophy, as well as anumber of periventricular hypodense lesions (fig la, b).

Case 2A 26 year old, right handed housewife presented with feel-ings of pins and needles in both hands, in February 1971,lasting 6 months. In December 1971 she noticed a dead andheavy feeling in her left foot, lasting 2 months. From April1972 she noticed a black spot in her right eye for-2 months,and during several weeks in the second half of 1972 she oncemore had transient paraesthesiae in the hands. Early in 1979her husband noticed loss of memory for telephone numbersand frequent mistakes in the names of familiar persons. InSeptember 1979, she developed a chronic progressiveinstability of gait and difficulties with fine motor tasks, suchas fine embroidery. Signs of cognitive dysfunction increasedduring the following years. By 1982, the patient had slurredspeech and severe instability of gait. Tendon reflexes wereincreased. Both the finger-nose and knee-ankle test werebilaterally ataxic. Sense of touch and vibration sense weredecreased in the legs.On neuropsychological assessment the patient was

cooperative and persistent. On the WAIS"7 the FSIQ was 69(estimated premorbid FSIQ 110). The VIQ of 83 wassignificantly below her premorbid abilities. The very poorresults in the performance subtests (PIQ = 58) could not be

explained by the motor impairment of the arms nor by theslow pace of work. Memory functions were impaired. On theWMS"8 her MQ (memory quotient) was 59 (estimated pre-morbid MQ 110). There was dyscalculia. Speech was slowand halting with dysarthria. Oral language was simple withsome problems of sentence structure and a slight namingimpairment. Word fluency (production of words beginningwith a given letter) was poor and perseverative. Languagecomprehension was intact. A written sentence containedseveral letter perseverations. The constructions (copyingthree- and two-dimensional designs) were, apart from tracesof difficult pencil manipulation, severely disturbed (fig2c).In summary, she was a woman aged 37, who was severelydeteriorated in all assessed components of cognition.Normal results were obtained from blood count, ESR,

serum urea, electrolytes and liver functions. The CSF con-tained 5 lymphocytes/mm3 with a cytological picture ofchronic infection. Isoelectric focusing of the CSF revealed anumber of oligoclonal bands not found in the serum,indicating intrathecal IgG synthesis. The CT scan showed anenlarged ventricular system, periventricular lesions andenlarged cortical sulci, indicating loss of white matter andglobal cortical atrophy (fig 2a, b).

Case 3A 27 year old, right handed female lawyer developed a con-stant frontal headache in January 1984, rapidly progressiveand associated with vomiting by March 1984. The patientlost interest in her work and often slept more than 12 hoursper day. According to her husband she developed slightdifficulties of speech. On admission she was somnolent, dis-oriented in space and had a slightly slurred speech. Thor-

1356


on Septem


j.com/

J Neurol N


ecember 1986. D

ownloaded from


Decline of cognition in multiple sclerosis: dissociable deficits

0 " 7 0. ~~~~~~~~~~-.

a

--S

"N

o Demyetinisationr ventrictesfl Oedema

0mLAi Demye inisationOedema

Fig 3 Case 3 (age 27 yr) (a) schematic representation of (b); (b) CT scans showing oedemaand ring-forming lesions ofdemyelination; (c) copy ofthree-dimensional design which is, apartfrom slightly uncertain stroke, structurally intact.

ough physical examination revealed no other neurologicalsigns or symptoms. Her headache and spatial disorientationdisappeared over a period of 3 weeks. In April 1984 she wasdischarged in a reasonably good condition. Four monthslater she had temporary visual loss of both eyes. She was

readmitted from February till May 1985 because of anotherrelapse in 1985 during which she developed axial ataxia andsigns of pyramidal involvement.At the time ofneuropsychological assessment (April 1985)

she was cooperative but somewhat childish in contact. Herwork pace was very low. On intelligence testing her WAISFSIQ was 108 (VIQ was 119, PIQ was 92). The PIQ was

definitely below her estimated premorbid level (estimated IQ120) and the response variability within and between theverbal subtests indicated that the VIQ had suffered as well,

but to a smaller extent than the PIQ. Registration of aurallypresented digits was normal (7 units) but of visuallypresented nonverbal material decreased. Reproduction ofsimple narrations was patchy but improved with multiplechoice questioning. Line drawings were poorly reproduced,which had to be attributed to insufficient recall of the stimulibecause copying was intact. Learning of word pairs wasinadequate. The Memory Quotient was 89 (estimated pre-morbid MQ 120). In mental arithmetic the patient knew thebasic processes but lost the elements of the sums. She madeperseverative errors in written arithmetic. She wrote dictatednumbers correctly and without hesitation. Language com-

prehension was intact but slow. Language production wascharacterised by word finding difficulty and slowness. Inconfrontation naming, searching for the correct word form

bo

_ it

1357


on Septem


j.com/

J Neurol N


ecember 1986. D

ownloaded from


1358

and benefit from first letter cueing were observed. A wordfluency task was qualitatively well performed. Written lan-guage (reading and writing) were intact. Drawings of three-and two-dimensional figures were correctly copied (fig3c),apart from an unsteady stroke which was a feature of allgraphic productions. Simple reaction times were long(476ms for visual and 374ms for auditory stimuli) andchoice reaction times were extremely long (565 ms). Insummary, she was a woman in whom cognitive instrumen-talities were intact but in whom slowness of processing wasincapacitating.

Extensive laboratory examination was unremarkable, asis reported elsewhere.20 All virological tests were normal.The CSF contained 9 cells/mm3 (6 lymphocytes). The IgGindex was elevated (1 0) and isoelectric focusing revealed apattern of oligoclonal bands. On the CT scan were oedemaand multiple hypodense hemispherical lesions visible, withwell-defined ring formation after contrast enhancement(fig 3a, b).

Discussion

Comparison with previous reportsWe have described three female, right handed patients(ages 27, 32 and 37 years) with multiple sclerosis. Therelapsing and remitting course of the clinical signsand symptoms and the laboratory data confirmed thediagnosis.Two patients were demented at age 32 and 37 years

respectively. In the first patient the cognitiveimpairment was of longer duration and far moreincapacitating than the motor symptoms (Kurtzkedisability score: 1). In patient 2 the mental changesstarted early in the disease, in a stage of moderatephysical invalidation, and the progression of mentaldeficits almost equalled the progression of physicalsymptoms (Kurtzke disability score: 4). Although theravaging cerebral process with multiple lesions in thethird patient (Kurtzke disability score: 3) seemedincompatible with normal mentation, cognition wasslow but otherwise undisturbed.

In early stages of multiple sclerosis progressivedecline of cognition is stated to be rare, except inacute cases.12 We know only two reports of severemental deterioration early in the disease.'1621 Bothconcerned patients (n = 7) comparable to our cases 1and 2. We are not aware of a previous report of apatient comparable to our case 3. The patients ofBergin"6 underwent formal testing, but no neuro-psychological data are mentioned. The patients ofYoung et a121 were tested with the WAIS. FSIQof these patients varied from 62 to 114. No furthersystematic neuropsychological assessment wasperformed in these patients, although WMS scoreswere mentioned to be poor for some patients.

In group studies intellectual deterioration has beenreported,8"' but denied by Marsh.6 He surveyed

Jennekens-Schinkel, Sandersdifferences in patient and test selection that mightaccount for the conflicting evidence on intelligence inmultiple sclerosis. Memory disturbances were docu-mented, but again in extremely variable fre-quencies.9 13 There is no unanimity concerning thepossible relation of associated motor defects to psy-chometric measures of cognition in these studies.

In our patients 1 and 2, in whom motor defectswere negligible or slight, a severe memory loss wasshown to be embedded in severe intellectual deterio-ration. In patient 3, deteriorated cognitive per-formance is more likely explained by slowness than bymotor handicap.

Cognitive decline in multiple sclerosis. dissociabledeficits?The differences in cognitive functioning between ourfirst two patients and our third patient suggesteddifferent psychopathological mechanisms. In a recentreview22 Cummings and Benson elaborated the dis-tinguishing features of cortical and subcortical23dementia. In cortical dementia the point of impact isin the instruments of cognition,24 the stored knowl-edge such as language, numeracy, and praxis. A car-dinal feature of subcortical dementia is said to bemental slowing.22 We studied reaction times in simpleand choice tasks in 40 multiple sclerosis patients andfound motor and not mental slowing.25 Lehmann,however, found in multiple sclerosis patients evidencefor inordinately prolonged reaction times if the taskload was increased, and attributed this to dis-turbances in the central association systems.26 Apartfrom mental slowing, forgetfulness, impaired abilityto manipulate acquired knowledge, changes of per-sonality and affect including apathy and depression,are characteristics of subcortical dementia that arestrikingly similar to Ombredane's careful descriptionof psychic alterations in patients with multiple sclero-sis, based on findings in 72% of his patients.27

Subcortical dementia is a controversial concept,28requiring neuro-anatomical and neuropsychologicalconstruct validation. Neuro-anatomic explanationsof the decreased cognitive function in multiple sclero-sis are abundant,3 8 13 but up till now few combinedstudies of cognition and of the neuro-anatomic sub-stratum have been performed. On CT investigationcortical atrophy and/or ventricular enlargement havebeen detected in about 50% of multiple sclerosispatients.29 30 The relation between CT scans and clin-ical findings is, however, known to be far from per-fect,31 32 and many more multiple sclerosis lesions arefound by advanced techniques of brain imaging suchas magnetic resonance imaging than by CT scan-ning.33 Recently positron emission tomography(PET) revealed low levels of oxygen utilisation in


on Septem


j.com/

J Neurol N


ecember 1986. D

ownloaded from


Decline of cognition in multiple sclerosis: dissociable deficitsboth grey and white matter of the cortex, particularlyin multiple sclerosis cases with cortical atrophy asseen by CT examination. Global intellectual declinewas related to widespread cerebral atrophy and it wassuggested that cortical atrophy can be a feature ofmultiple sclerosis in the absence of obvious whitematter lesions.14Our three patients suffered from acquired intel-

lectual impairment. In the first, two specific deficitswere difficult to disentangle within the picture of gen-eral and severe dementia. However, slowness of cog-nition as well as cognitive impairment strictu sensu,such as disturbed numeracy and constructionalapraxia were present. The behaviour of case 1 showedsigns of personality changes in the sense of puerileeuphoria. Tentatively following Albert's23classification of dementia, these impairments mightbe interpreted as indicative of cortical and subcorticaldementia. Both patients had hypodense peri-ventricular lesions in addition to severe cortical atro-phy and severe ventricular enlargement on the CTscans. Patient 3, on the contrary, had devastatingwhite matter lesions without signs of cortical atrophy.Although achieving below her prior abilities on psy-chometric tests of intelligence and memory cognitionwas essentially intact, her work pace was significantlyslowed. She had difficulty retrieving learned materialof whatever kind but no disorder of cognitive instru-mentalities, and she rather seemed to show subcor-tical dementia.The question may be raised whether disease

duration explains the different cognitive patterns,patients I and 2 having much longer histories thanpatient 3. We cannot answer this question on the basisof the present findings. However, in a group of 40multiple sclerosis patients with disease durationsvarying from I to 48 years, we found no evidence ofmental deterioration in relation to duration of illness.Finding duration of illness related only to physicaldisability, Marsh6 also concluded that chronic multi-ple sclerosis need not be associated with intellectualdeficit. The presence of considerable oedema inpatient 3 may have affected cognitive performance.The important point is that patient 3 does not showso-called cortical signs of cognitive decline, notwith-standing considerable oedema.

Disputes about the nature, and even the very exis-tence, of cognitive disorders in multiple sclerosis maybe attributed not only to differences in disease vari-ables but also to reliance on tests designed to discoverindividual differences in performance, and neglect ofthe search for alterations in component mental pro-cesses. Our three case histories demonstrate thatcognitive decline in multiple sclerosis may have dis-tinct neuropsychological patterns which appear to berelated to CT findings. They strongly suggest that

research on the relation between structural and clin-ical alterations should be a combined effort in whichadvanced techniques of brain imaging are applied inclose combination with psychometric assessment andanalysis of deficits in cognitive processing.

The authors thank Professor Dr G W Bruyn, Dr F GI Jennekens and Dr A R Wintzen for valuable adviceand linguistic revision of a previous draft of thispaper. Dr W E Vliegenthart (neurologist, Utrecht)allowed us to study his patient (case 3). The neuro-psychological assessment of patient 2 was supervisedby Dr J B K Lanser (Head, NeuropsychologyDepartment). Mrs G J van der Giessen and A JRhijnsburger prepared the illustrations.

References

1 Vulpian A. Maladies du Systeme Nerveux. Vol 2. Paris:Doin, 1879:704-9.

2 Beatty PA, Gange JJ. Neuropsychological aspects ofmultiple sclerosis. J Nerv Ment Dis 1977;161:42-50.

3 Carroll M, Gates R, Roldan F. Memory impairment inmultiple sclerosis. Neuropsychologia 1984;12:297-302.

4 Goldstein G, Shelly CH. Neuropsychological diagnosisof multiple sclerosis in a neuropsychiatric setting.J Nerv Ment Dis 1974;158:280-90.

5 Ivnik RJ. Neuropsychological test performance as afunction of the duration of MS-related symptom-atology. J Clin Psychiatry 1978;39:304-12.

6 Marsh GG. Disability and intellectual function inmultiple sclerosis. J Nerv Ment Dis 1980;168:758-62.

7 Matthews CG, Cleeland CS, Hopper CL. Neuro-psychological patterns in multiple sclerosis. Dis NervSyst 1970;31:161-70.

8 Peyser JM, Edwards KR, Poser CM, Filskov SB.Cognitive functioning in patients with multiplesclerosis. Arch Neurol 1980;37:577-9.

9 Rao SM, Hammeke ThA, McQuillen MP, Khatri BO,Lloyd D. Memory disturbance in chronic progressivemultiple sclerosis. Arch Neurol 1984;41:625-31.

10 Reitan RM, Reed JC, Dyken ML. Cognitive psycho-motor and motor correlates of multiple sclerosis.J Nerv Ment Dis 1971;153:218-24.

11 Jambor KL. Cognitive functioning in multiple sclerosis.Br J Psychiatry 1969;115:765-75.

12 Matthews WB, Acheson ED, Batchelor JR, Weller RO.McAlpine's Multiple Sclerosis. Edinburgh: ChurchillLivingstone, 1985:107-8.

13 Grant J, McDonald WI, Trimble MR, Smith E.Deficient learning and memory in early and middlephases of multiple sclerosis. JNeurol NeurosurgPsychiatry 1984;47:250-5.

14 Brooks DJ, Leenders KL, Head G, Marshall J, Legg NJ,Jones T. Studies on regional cerebral oxygen util-isation and cognitive function in multiple sclerosis.J Neurol Neurosurg Psychiatry 1984;47: 1182-91.

15 Heaton RK. Neuropsychological findings associatedwith two clinical courses of multiple sclerosis.

1359


on Septem


j.com/

J Neurol N


ecember 1986. D

ownloaded from


1360

Abstract, International Neuropsychological SocietyBulletin, Nov 1984:56.

16 Bergin JD. Rapidly progressing dementia in dissem-inated sclerosis. J Neurol Neurosurg Psychiatry1957;20:285.

17 Wechsler D. Manualfor the Wechsler Adult IntelligenceScale. New York: The Psychological Corporation,1955. Dutch revision: Stinissen J, etal. Amsterdam:Swets & Zeitlinger.

18 Stutsman C. Mental Measurement ofPreschool Children:Dutch instruction. Nijmegen: Berkhout, 1931.

19 Wechsler D, Stone C. Wechsler Memory Scale. NewYork: The Psychological Corporation, 1945.

20 Vliegenthart WE, Sanders EACM, Bruyn GW. Anunusual CT-scan appearance in multiple sclerosis.J Neurol Sci 1985;71:129-34.

21 Young AC, Saunders J, Ponsford JR. Mental change as

an early feature of multiple sclerosis. J Neurol Neuro-surg Psychiatry 1976;39:1008-13.

22 Cummings JL, Benson DF. Subcortical dementia, an

emerging concept. Arch Neurol 1984;41:874-9.23 Albert ML, Feldman RG, Willis AL. The subcortical

dementia in supranuclear palsy. J Neurol NeurosurgPsychiatry 1974;37: 121-30.

24 Editorial. Cognitive Neuropsychology 1984;1: 1-8.25 Jennekens-Schinkel A, Sanders EACM, Lanser JBK.

Neuropsychological evaluation of fatiguability inMultiple Sclerosis. Neuroscience Letters suppl 22

Jennekens-Schinkel, Sanders

Si -S360. Abstracts 9th European NeuroscienceCongress. Amsterdam: Elsevier, 1985:589.

26 Lehmann HJ, Glockner RJ. Cerebral disconnection inmultiple sclerosis. Eur Neurol 1972;8:257-69.

27 Ombredane A. Sur les Troubles Mentaux de la Scleroseen Plaques. Paris: Presses Universitaires de France,1929.

28 Freedman M, Albert ML. Subcortical dementia. In:Vinken PJ, Bruyn GW, Klawans HL, eds. Handbookof Clinical Neurology, vol 46. Frederiks JAM, co-editor, Neurobehavioural Disorders. Amsterdam:Elsevier, 1985:311-6.

29 Gyldensted G. Computer tomography of the cerebrumin multiple sclerosis. Neuroradiology 1976;12:33-42.

30 Cala LA, Mastaglia FL, Black JL. Computerized tomo-graphy of brain and optic nerves in multiple sclerosis.J Neurol Sci 1978;36:411-26.

31 Reisner T, Maida A. Computerized tomography inmultiple sclerosis. Arch Neurol 1980;37:475-7.

32 Loizou LA, Rolfe EB, Hewazy H. Cranial computedtomography in the diagnosis of multiple sclerosis.J Neurol Neurosurg Psychiatry 1982;45:905-12.

33 Kelly R. Clinical aspects of multiple sclerosis. In: VinkenPJ, Bruyn GW, Klawans HL, eds. Handbook ofClinical Neurology, vol 47. Koetsier JC, co-editor,Demyelinating Diseases. Amsterdam: Elsevier,1985:49-78.


on Septem


j.com/

J Neurol N


ecember 1986. D

ownloaded from


dissociable - bmjjournalofneurology, neurosurgery, andpsychiatry 1986;49:1354-1360...

Documents