Journal of Neurology, Neurosurgery, and Psychiatry 1990;53:142-145

Neuropsychological assessment in patients withrelapsing-remitting multiple sclerosis and mildfunctional impairment: correlation with magneticresonance imaging

G P Anzola, L Bevilacqua, S F Cappa, R Capra, L Faglia, E Farina, G Frisoni, C Mariani,M P Pasolini, L A Vignolo

AbstractForty one moderately impaired patientswith clinically confirmed multiplesclerosis (MS) and a relapsing-remittingcourse were submitted to a neuropsycho-logical battery and magnetic resonanceimaging (MRI) to correlate the neuro-psychological performances with thedegree of cerebral demyelination. Theneuropsychological results were indica-tive of a very mild overall impairment.The patients were subdivided into twogroups (extensive periventricular de-myelination or discrete lesions on MRI)and the results of neuropsychologicaltests compared. Patients with extensiveperiventricular demyelination had aninferior performance on concept forma-tion, non-verbal reasoning and verbalmemory tests.

Clinica Neurologicadell'UniversitA diBresciaG P AnzolaS F CappaRT CapraL FagliaG FrisoniM P PasoliniL A VignoloDivisione NeurologicaOspedale Niguarda CAGranda Milano,L BevilacquaIstituto di ClinicaNeurologicaUniversitA di MilanoE FarinaC Mariani

Correspondence to:L A Vignolo MD, ClinicaNeurologica, II Neurologia,Spedali Civili, 25100 BresciaBS, Italy.Received 29 November 1988and in revised form 9 June1989.Accepted 17 July 1989

Magnetic Resonance Imaging (MRI) of thebrain is a sensitive tool to detect demyelinatinglesions in multiple sclerosis (MS). In clinicallydefinite MS, MRI demonstrates lesions in aproportion ranging from 78/o' to 99%2 ofcases; in suspected MS3 lesions have beenfound in 62% of patients.The correlation of MRI findings with the

clinical features report conflicting results.Some authors' found no correlation witheither the duration of illness or the disabilityscore, while others78 reported a positivecorrelation between severity of MRI lesionsand disability score. Moreover, recent serialstudies in relapsing patients have documentedchanges on MRI unaccompanied by relevantnew neurological symptoms or signs.910One relevant aspect ofMS disability, which

has been emphasised in recent years, is neuro-psychological impairment. Cognitive deficitscan be found in a substantial number of MSpatients11 and do not seem to be related either tolength of illness or severity of the functionalimpairment."'2- Studies investigating therelationship between neuropsychological de-ficits and structural brain damage are scanty.Rao et al " found a relationship between CT-assessed ventricular enlargement and intellec-tual and memory dysfunction in 47 patientswith chronic progressive MS. MRI has beenemployed by Medaer et al 16 and Huber et a 17to investigate the extent of brain involvement

in patients with clinically and/or psycho-metrically assessed dementia, with differentresults: in the former study patients withcognitive impairment showed an overallgreater degree of demyelination, while in thelatter it was only the severity of corpuscallosum atrophy that differentiated thedemented patients.The aim of the present research is to inves-

tigate the relationship between MRI involve-ment and neuropsychological performance in agroup of outpatients with relapsing-remitting,clinically definite MS and mild overall func-tional impairment.

Material and methodsPatientsForty one subjects were selected out of thepatient population attending three MS clinics,on the basis of the following criteria:1) Clinically definite MS according to Poser'scriteria. 182) Relapsing-remitting course.3) Kurtzke disability score"9 equal or inferiorto 6.4) Educational level of at least five years.5) Right-handedness (Edinburgh Inventoryscore = 10)206) Willingness to participate in the study.The patients' characteristics are summarised intable 1.

Neuropsychological batteryThe following tests were administered in thesame sequence in a single session lastingapproximately two hours. The patients hadreceived no medication for at least two daysbefore testing.Token Test2' A sensitive test to detect auditorycomprehension impairment. The score is thenumber of correct responses (range 0-36).Judgment of Line Orientation22 A visuo-spatialmatching task, sensitive to right hemispheredamage. The score is the number of correctresponses (range 0-30).

Table I Patients' characteristics (N = 41)

Sex (Male/Female) 10/31Age (years) mean 34 (range 17-56)Years of schooling mean 11 (range 5-23)Kurtzke Disability Status

Score mean 2 (range 0- 6)Time since onset of symptoms

(years) mean 6-8 (range 01-21)

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Neuropsychological assessment in patients with relapsing-remiuing multiple sclerosis

Table 2 Comparison (Mann- Whitney U-test) ofdemographic, clinical and neuropsychological data inpatients without (Group 1) and with (Group 2)extensive periventricular demyelination. Mean (range)

Group I Group 2(n= 19) (n= 22) U p

Age (years) 32 (17-56) 34-8 (20-56) 181 5 nsEducation

(years) 12 3 (5-18) 10-1 (5-23) 146-5 nsKurtzke Score 2 3 (0- 6) 2.0 (0- 6) 188 nsZung Score 42 9 (24-79) 43-9 (24-74) 196 5 nsShort Tale 15 7 (6-21) 12 6 (4-21) 123 0 012Raven's PM 32 1(20-36) 27 9 (12-36) 112 0 005Corsi

Supraspan 10-2 (4-18) 10 1 (3-18) 199 5 nsWeigl 12 7 (9-15) 10 1 (0-15) 122 5 0011Benton 22-9 (18-29) 22 7 (10-30) 208 ns

Short Tale23 A verbal memory test similar to the"logical memory" subtest of the WechslerMemory Scale. The score is the mean numberof items recalled immediately after presenta-tion and 10 minutes later (range 0-28).Raven's Coloured Progressive Matrices24 A nonverbal reasoning test. The score is the numberof correct responses (range 0-36).Digit Span From the Wechsler AdultIntelligence Scale,25 a verbal short termmemory test. The score is the longest sequencerecalled in correct order.Corsi Span25 A sequential block-tapping task,which is considered the visuo-spatialequivalent of Digit Span. Score as for digitspan.Verbal Fluency26 Assessing the timed produc-tion of words after phonemic and semanticcues. The score is the total number of accept-able responses.Corsi Supra-span27 A test of spatial non-verballearning. The score is the number of trials toreach the criterion (three consecutive correctrepetitions of an eight-block sequence) up to amaximum of eighteen trials.Weigl Test28 A sorting test assessing conceptformation as well as "set shifting" abilities.

The score reflects the number of correctlyidentified categories (range 0-15).Zung Depression Rating Scale29 A self-adminis-tered questionnaire.

MRI studyAll the MRI examinations were performedemploying a 0 5 T superconductive unit(Philips Gyroscan S 5), capable of performinginversion recovery (IR) and spin echo (SE)sequences. In a standard examination multipleechoes (ME) were employed: pulse sequenceshad a repetition time (TR) varying from 500 to800 ms with an echo time (TE) from 50 to200 ms. Four images were usually obtained foreach sequence. Pictures were acquired on 256x 256 matrix. Slice thickness varied from 6 to8 mm.The routine examination consisted of axial

slices from the foramen magnum up to thevertex and sagittal slices through the midlineincluding the cervical spinal cord. Coronalslices were also frequently obtained in thepertinent position.'

All the patients had been submitted to MRIin a period from two days to six months beforeneuropsychological testing. Patients who hadexperienced new clinical symptoms or signs inthe period between MRI and neuropsycho-logical testing had a repeat MRI scan. This wascarried out to improve clinical-anatomicalcorrelation, even if it has been recently shownthat MRI modifications may not be associatedwith clinical evidence.9 10The MRI films were scored using the

method proposed by Ormerod,2 which yields anumeric estimate of the severity of lesions in 15discrete standardised areas of the brain. Theevaluation of the MRI films was performedblindly to both the clinical conditions and theneuropsychological results for each patient.

Figure 1 (a and b) MRIof a patient with multipleisolated lesions (Group 1).

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Anzola, Bevilacqua, Cappa, Capra, Faglia, Farina, Frisoni, Mariani, Pasolini, Vignolo

Figure 2 (a and b) MRIof a patient with extensiveperiventriculardemyelination (Group 2).

ResultsThe scores on neuropsychological testing ofMS patients were scrutinised using publishednorms.2'128 Since none of the patients was

impaired on the Token Test and the Digit andCorsi Span, these data were not analysedfurther.Non-parametric correlations (Spearman

rank correlation coefficients) were computedfor the entire sample between the MRI abnor-mality index and scores (corrected for age,education and, when appropriate, sex) on selec-ted tests (Raven, Weigl, Short Tale, Kurtzkedisability score and Zung Depression Rating).The only significant correlation was betweenthe severity of MRI involvement and perfor-mance on Weigl's Test (p < 001). Kurtzkeand depression scores yielded no significantcorrelations with MRI involvement. Furthercorrelations were attempted between severityof left or right hemispheric involvement andperformances, respectively, on verbal fluencyand on line orientation and supraspan spatialtests, with non significant results.

Patients were then subdivided into twogroups, based on the presence of an extensive,irregular periventricular demyelination (a pat-tern of abnormality which has been suggestedas characteristic of MS) (N = 22) or, alter-natively, of single or multiple discrete lesions inthe periventricular or extraperiventricularregions (N = 19). Figures 1 and 2 show an

example of multiple isolated lesions and exten-sive periventricular demyelination respec-tively.The two groups did not differ with respect to

age, education, Kurtzke disability score andZung depression score. The demographic andclinical data are shown in table 2, together withthe results of neuropsychological tests. A sig-nificantly inferior performance in concept for-mation (Weigl's test), non-verbal reasoning(Raven's PM) and verbal memory (Short tale)tests was present in the patients with extensiveperiventricular demyelination.

DiscussionAt variance with reports of other series24 theneuropsychological results showed a very mild

overall impairment in our group of multiplesclerosis patients. This apparent discrepancy isprobably due to the characteristics of thepresent patient population. The majority ofprevious studies included patients with a widerrange of physical disability. Moreover, with afew exceptions,'5 it is often unclear whetherthe patients presented a chronic progressive ora relapsing-remitting course: this is par-ticularly relevant since there is considerableevidence that cognitive dysfunction is par-ticularly associated with a chronic/progressivedisease course.03' The selection of patients inthe ambulatory stage (Kurtzke score equal to orless than 6) and with a relapsing-remittingcourse may have excluded the majority ofpatients with MS-related dementia. Indeed, ofthe 41 patients only two had been consideredby the attending neurologists as cognitivelyimpaired on clinical grounds: both showedextensive periventricular demyelination.

Nevertheless, we found an inferior perfor-mance on abstract reasoning, concept forma-tion and verbal memory tests in patients withevidence of extensive demyelination. Visuo-spatial performance and language were gen-erally spared.The pattern of neuropsychological impair-

ment in MS patients is similar to the so called"subcortical dementias"."1 This groupincludes patients with different conditions,such as Huntington's chorea, progressivesupranuclear palsy and even Parkinson's dis-ease: intellectual slowing, attentional prob-lems, impairment in abstract reasoning, prob-lem solving and memory dysfunction are thehallmarks of this clinical picture."2 Studies, inparticular from positron emission tomo-graphy,33 suggest an association between "sub-cortical dementia" and a deactivation of thefrontal lobes, due to widespread interruption ofafferent connections coming from subcorticalstructures. The present study supports thishypothesis.

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