Control of visually guided saccades in multiple sclerosis: Disruption to higher-order processes

Ocular motor abnormalities are a common feature of multiple sclerosis (MS), with more salient deficits reflecting tissue damage within brainstem and cerebellar circuits. However, MS may also result in disruption to higher level or cognitive control processes governing eye movement, including attentional processes that enhance the neural processing of behaviourally relevant information. The attentional control of eye movement was investigated in 25 individuals with MS and a comparable number of neurologically healthy individuals matched for age and IQ. This entailed an evaluation of distractor-related effects on the generation of both unpredictable and predictable visually guided saccades, as well as an evaluation of the effects of presenting endogenous cues prior to target onset. For unpredictable saccades, we revealed an exaggerated distractor effect in MS, with saccade latencies prolonged and endpoints less accurate in the presence of a visual distractor. Predictable saccades tended to be hypometric for MS patients, although we found no significant distractor effects. For endogenously cued saccades, we found no group differences in latency following a valid cue, but an exaggerated increase in latency following invalid cues for MS patients. MS patients also generated a significantly greater proportion of erroneous responses to cue stimuli. These ocular motor characteristics demonstrate considerable sensitivity with respect to evaluating attentional deficits in MS, evident even in the absence of clinical signs of disease.     

Oligoclonal band number as a marker for prognosis in multiple sclerosis.

The natural course of disease in multiple sclerosis varies. Multiple sclerosis that is clinically apparent but causes minimal disability over time has been labeled benign multiple sclerosis. The ability to predict the subsequent clinical course of multiple sclerosis on the basis of clinical and other supportive data at presentation would be invaluable. In this article we report our findings based on a retrospective analysis of 1800 patients diagnosed as having multiple sclerosis, of which 44 patients met our inclusion criteria. There was a suggestion that a low or absent number of oligoclonal bands in the cerebrospinal fluid at the time of diagnosis predicts a better prognosis. However, quantification of oligoclonal bands in cerebrospinal fluid remains an insensitive prognostic indicator and must not be used to influence decisions regarding therapeutic options.     

The flight of colors test in multiple sclerosis

Flight of colors (FOC), the rapidly changing series of colored afterimages perceived when a bright light briefly strikes the eye, is impaired or absent in patients with lesions affecting central visual fields, especially optic neuropathies (ONs). The effectiveness of a bedside test of FOC using a pocket flashlight was compared with that of pattern-reversal visual evoked responses (PRVERs) in examining 74 subjects): 20 controls, seven patients with ON not due to multiple sclerosis (MS), 26 patients with MS, and 21 patients with possible MS and no clinical ON. The FOC test correctly identified 95 of 99 normal eyes and 45 of 49 eyes with ON, and accurately diagnosed 140 (95%) of 148 eyes overall. In 84 eyes examined by PRVER and FOC, the results agreed in 73 cases (87%), including those of subclinical ON.     

Evoked potentials to test a treatment of chronic multiple sclerosis

Multimodal evoked potentials (EPs) were obtained serially in 57 patients with multiple sclerosis enrolled in a double-blind, controlled study of hyperbaric oxygen. We encountered drawbacks in the use of EPs in monitoring effects of a treatment for chronic multiple sclerosis. Limitations include a relatively arduous testing protocol and the significant occurrence of ambiguous and frankly unreproducible results. Test/retest variability is large in stable patients. There is poor correspondence between EP changes and changes of clinical function as well as among EP modalities. Whether EP measurements ultimately prove to be useful in testing new therapies awaits the development of a truly effective treatment, the effects of which can be shown despite these factors and limitations.     

Paced visual serial addition test in multiple sclerosis

The paced auditory serial addition test (PASAT), a subtest of the multiple sclerosis functional composite score (MSFC), is increasingly used in the evaluation of cognitive function in multiple sclerosis (MS). While patient acceptance for the PASAT is low, its visual version, the paced visual serial addition test (PVSAT), is perceived to be better tolerated. The aim of this study was to investigate the interchangeability of PVSAT and PASAT in the evaluation of cognitive function in MS. Twenty-one normal controls and 50 patients with clinically definite MS were tested with PASAT and PVSAT. Both for PASAT and PVSAT, 3 and 2-second versions of two parallel test forms were used. In the PVSAT, the PASAT stimuli were shown on a computer screen. Patients were also tested with the other two MSFC subtests, i.e. the nine-hole pegboard test and timed 25-foot walk test, to calculate MSFC scores. PASAT-3 correlated highly with both PVSAT-3 and PVSAT-2. MSFC-v scores calculated with PVSAT-2 and PVSAT-3 values correlated highly with MSFC scores calculated with PASAT-3 results. The results suggest that the PVSAT can be used as an alternative for the PASAT in the MSFC.     

The rapid assessment of visual dysfunction in multiple sclerosis.

A consecutive series of patients with normal activity and a diagnosis of multiple sclerosis (10 male and 31 female) underwent extensive ophthalmological examination including visual evoked potentials (VEPs) and a new test of contrast sensitivity, which is described in detail. Seventy three per cent of patients had abnormal contrast sensitivity and 83% had abnormal VEPs. There was no association between abnormalities of the two types, but patients who had impaired contrast sensitivity and normal VEPs were younger than those whose contrast sensitivity was normal but whose VEPs were not. The test of contrast sensitivity (which took less than 5 minutes to administer) was the only examination to reveal visual abnormalities in all nine patients with a history of optic neuritis, and would be a useful supplementary test in the examination of patients with suspected multiple sclerosis.     

Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis

OBJECTIVE: The apolipoprotein E (APOE) polymorphism is known to impact on various neurologic disorders and has differential effects on the immune system and on CNS repair. Previous findings concerning a possible modulation of the clinical course of MS have been inconsistent, however. METHODS: In a cross-sectional study, the authors investigated 374 patients with clinically definite MS and a disease duration of at least 3 years and related their clinical and demographic findings to the allelic polymorphism of the APOE gene. The genotype distribution of patients with MS was compared with a cohort of 389 asymptomatic, randomly selected elderly volunteers. RESULTS: The authors found no significant differences in the distribution of genotypes between patients with MS and controls. However, patients with MS with the epsilon4 allele (n = 85) had a significantly higher progression index of disability (0.46 +/- 0.4 versus 0.33 +/- 0.26; p < 0.004) and a worse ranked MS severity score (5.1 +/- 1.9 versus 5.7 +/- 1.7; p = 0.05) than their non-epsilon4 counterparts, despite significantly more frequent long-term immunotherapy in epsilon4 carriers (74% versus 58%; p < 0.007). The annual relapse rate in epsilon4 carriers (0.87 +/- 0.56) was significantly higher than in patients with MS without an epsilon4 allele (0.71 +/- 0.47; p = 0.03). CONCLUSIONS: These results suggest no effect of the APOE genotype on susceptibility to MS, but indicate an association of the APOE epsilon4 allele with a more severe course of the disease.     

Neglect in a patient with multiple sclerosis

We report a patient with multiple sclerosis (MS) who developed left-sided neglect. Although MS is commonly associated with mental status changes, we believe that this is the first reported case of hemineglect. The deficit is probably related to the location, acuteness, size, and right hemispheric predominance of lesions in this patient.     

Glioma in a patient with multiple sclerosis

The simultaneous occurrence of multiple sclerosis and a primary brain neoplasm is exceptional: only 32 cases have been reported in the literature. We report the case of a 30-year-old woman with multiple sclerosis proven for 10 years who developed a grade II astrocytoma revealed by MRI. At the pathology examination, there was no cellular continuity with areas of demyelinized white matter. Unlike the hypothesis put forward in certain publications describing this association that argue for an induction link between these two entities, our case did not demonstrate any spatial or temporal relationship suggestive a common cause.     

BCcogSEP: a French test battery evaluating cognitive functions in multiple sclerosis

In French language, there is no standardized procedure to assess cognitive function in patients with multiple sclerosis (MS). Such an assessment is however very useful to determine the consequences of the disease on cognitive function, to evaluate the disease progression and the consequences of usual treatments on cognition. This study aimed to develop and validate a French language battery based on "the Brief Repeatable Battery of Neuropsychological tests for Multiple Sclerosis" (BRB-N) often used in other countries. In an initial phase, the battery was composed of the French version of the 5 BRB-N tests to which were added 4 tests assessing immediate and working memory as well as executive function. 52 healthy control subjects (20-50 years) participated in the study. A principal component analysis (PCA) of their data examined the contribution of each test into the battery. 93 other healthy subjects participated in a second phase where analyses of variance were carried out to investigate the effect of the main demographical variables. Finally, the performance of two patient groups (20 with a EDSS score3) was compared to the healthy controls in order to investigate the ability of our battery to detect cognitive impairment in MS patients. The PCA showed that each test, except one, had a specific contribution to the battery. The final battery (BCcogSEP) was thus comprised of 8 tests. MANOVA and ANOVA showed significant effects of age, sex and educational level on performance. In consequence, a procedure allowing to take into account these factors was developed. The battery was able to detect cognitive impairment in MS patients, even when the disease is not severe. In this case, deficits were observed in tests assessing executive function, information processing speed, immediate and working memory. This short battery with reliable psychometric qualities allows the interpretation of a MS patient's performance considering his/her demographical characteristics and is able to detect cognitive abnormalities even in case of mild physical handicap.     

Transferrin in patients with multiple sclerosis: a comparison among various subgroups of multiple sclerosis patients

OBJECTIVES: To compare cerebrospinal fluid (CSF) and serum transferrin (Tf) concentrations, transferrin quotient and index in various subgroups of MS patients. MATERIAL AND METHODS: CSF and serum transferrin concentrations, transferrin quotient QTf (i.e. CSF transferrin/serum transferrin x 10(3)) and index (QTf/Qalbumin) were determined in a group of 51 patients with clinically definite or probable multiple sclerosis (MS). Patients were subdivided according to the disease form (relapsing-remitting = RR, secondary progressive = SP, primary progressive = PP; patients with RR form were further subdivided into those in the attack and those in remission), disease severity (EDSS 0-5.5, EDSS 6.0-10.0), its treatment (non-treated - including patients treated with vitamins and/ or vasodilators only, treated - i.e. glucocorticoids and/or immunosuppressants and/or (exceptionally) beta-interferon), disease duration (0-2 years, >2-10 years, > 10 years) and sex. Correlation of transferrin values with age was also performed. RESULTS: Serum transferrin was somewhat lower and significantly more frequently subnormal in PP patients in comparison with the SP form and the RR form in remission. Transferrin index was significantly higher in the PP form than in the RR as well as the SP form. Transferrin quotient was significantly more frequently subnormal in patients in remission compared to those in the attack of the RR disease. CSF transferrin as well as transferrin quotient were more frequently subnormal in patients with short disease duration (0-2 years) than in patients with longer disease duration; these parameters, however, correlated also significantly with age. CSF transferrin and transferrin quotient were higher in male than in female patients. CONCLUSION: The authors conclude that evaluation of transferrin in MS patients - along with albumin - may help to differentiate among various MS subgroups, since there are significant differences among RR, SP and PP forms. For this purpose, however, other CSF protein fractions should be evaluated in parallel in order to obtain more complex information and to establish a panel of examinations enabling multiple statistical analyses. Transferrin evaluation in MS may also be of significant theoretical interest, since transferrin is known to be involved in the regulation of iron metabolism and it may have a protective role against the oxidative stress. Moreover, transferrin is a growth factor important for proliferation of activated T lymphocytes. By means of the use of transferrin quotient and especially transferrin index, it may be possible to estimate the proportion of intra-CNS-synthesized transferrin and/or rate of specific transferrin transport across the blood-CSF barrier. Further studies are, however, needed for such an evaluation.