Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS
Huijbregts SC, Kalkers NF, de Sonneville LM, de Groot V, Reuling IE and Polman CH;
Commented by , 23 Aug 2004
Background
Cognitive impairment is a common symptom in MS, present in 40 – 60 % of all cases. It concerns most patients and counseling is important although difficult, due to the disabling nature of the symptom. Former studies have shown that progressive MS has a higher prevalence of cognitive deficits, but the qualitative differences between relapsing remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) have only been described in one study (ref. 1). The current study aims at describing these differences using a large sample size.
Aim
To describe cognitive dysfunction in RRMS, SPMS, and PPMS relative to healthy controls, and to assess if there is heterogeneity between these subtypes.
Methods
The authors studied 234 patients with MS (subgroup distribution: RRMS (n=108), SPMS (n=71) and PPMS (n=55)), as well as 67 control subjects. Kurtzke's EDSS was used to assess the neurological disability. For neuropsychological evaluation the authors used the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), which measures verbal learning, visuospatial learning, memory, information-processing speed, complex visual ability, calculation, and verbal fluency. The statistical approach was correlation analysis between clinical data and task performance/demographic data, and multivariate analysis between controls and MS patients as well as between subgroups.
Results
1. Age, disability, and disease duration correlated negatively with task performance.
2. In the multivariate analysis there were large differences between normal subjects and MS patients (p<0.001).
3. Relative to controls, RRMS patients performed poorer in higher order working memory processes, and SPMS and PPMS patients performed poorer in all tests.
4. The multivariate analysis of subgroups also showed large between-group differences.
5. SPMS patients performed poorer than PPMS in higher order working memory tests, except for task requiring speed of information processing.
6. RRMS patients generally performed better than the progressive subtypes, although verbal fluency was impaired.
Discussion
The study shows that cognitive deficits are most significant in SPMS patients, followed by PPMS and RRMS patients, and that there is heterogeneity between cognitive impairment of MS subgroups. The authors speculate that the degree of white matter pathology may determine these differences, although the study provides no relevant measurements in this regard.
It has been shown that cerebral activation is significantly changed, even in the initial stages of the disease with limited white matter pathology (ref. 2). It has also been shown that axonal/neuronal loss, and not white matter changes, is related to MS related fatigue (ref. 3) which again may be related to cognitive disability.
It would have been interesting if the authors had presented relevant MRI data, in order to determine if axonal loss or white matter pathology could explain the observed changes.
The authors hypothesize that loss of information-processing speed most significantly distinguish the cognitive profile of MS subtypes, which is interesting and may give rise to future studies elucidating the pathophysiology of these changes.
The study does not provide surprising new results, but the conclusions are helpful and important with regard to counseling in MS.
References
1. Gaudino EA, Chiaravalloti ND, DeLuca J, Diamond BJ. A comparison of memory performance in relapsing-remitting, primary progressive and secondary progressive, multiple sclerosis. Neuropsychiatry Neuropsychol Behav Neurol 2001;14:32-44.
2. Rocca MA, Mezzapesa DM, Falini A, Ghezzi A, Martinelli V, Scotti G, Comi G, Filippi M. Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage 2003;18:847-55.
3. Tartaglia MC, Narayanan S, Francis SJ, Santos AC, De Stefano N, Lapierre Y, Arnold DL. The relationship between diffuse axonal damage and fatigue in multiple sclerosis. Arch Neurol 2004;61:201-7.