Modeling of cognitive impairment by disease duration in multiple sclerosis: a cross-sectional study.

BACKGROUND/AIMS: Large-scale population studies measuring rates and dynamics of cognitive decline in multiple sclerosis (MS) are lacking. In the current cross-sectional study we evaluated the patterns of cognitive impairment in MS patients with disease duration of up to 30 years. METHODS: 1,500 patients with MS were assessed by a computerized cognitive battery measuring verbal and non-verbal memory, executive function, visual spatial perception, verbal function, attention, information processing speed and motor skills. Cognitive impairment was defined as below one standard deviation (SD) and severe cognitive impairment as below 2SD for age and education matched healthy population norms. RESULTS: Cognitive performance in our cohort was poorer than healthy population norms. The most frequently impaired domains were information processing speed and executive function. MS patients with secondary-progressive disease course performed poorly compared with clinically isolated syndrome, relapsing-remitting and primary progressive MS patients. By the fifth year from disease onset, 20.9% of patients performed below the 1SD cutoff for impairment, p=0.005, and 6.0% performed below the 2SD cutoff for severe cognitive impairment, p=0.002. By 10 years from onset 29.3% and 9.0% of patients performed below the 1SD and 2SD cutoffs, respectively, p=0.0001. Regression modeling suggested that cognitive impairment may precede MS onset by 1.2 years. CONCLUSIONS: The rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health.

Single dose of methylphenidate improves cognitive performance in multiple sclerosis patients with impaired attention process.

BACKGROUND AND PURPOSE: Attention is one of the major cognitive domains adversely affected in multiple sclerosis (MS). The aim of the current study was to determine the effect of a single dose of methylphenidate on cognitive performance of MS patients with significant attention deficit. METHODS: In a double-blind placebo-controlled study design, 26 MS patients with impaired attention were randomly assigned to receive a single dose of 10 mg methylphenidate or placebo. Attention was assessed using the paced auditory serial addition test for 3 and 2 s (PASAT3'' and PASAT2'') at baseline and 1 h after drug/placebo administration. RESULTS: Methylphenidate significantly improved performance of both PASAT3'' and PASAT2'' tests by 22.8% and 25.6% respectively (p<0.001), while no significant changes were observed in placebo treated patients. CONCLUSION: Administration of a single dose of methylphenidate significantly improved attention in MS patients with considerable attention deficit.

Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Intravenous immunoglobulin (IVIg) has been reported to reduce disease activity in patients with relapsing-remitting multiple sclerosis. We assessed the effect of IVIg treatment in patients after the first neurological event suggestive of demyelinative disease and evaluated the occurrence of a second attack and dissemination in time demonstrated by brain magnetic resonance imaging within the first year from onset. METHODS: We conducted a randomized, placebo-controlled, double-blind study in 91 eligible patients enrolled within the first 6 weeks of neurological symptoms. Patients were randomly assigned to receive IVIg treatment (2-g/kg loading dose) or placebo, with boosters (0.4 g/kg) given once every 6 weeks for 1 year. Neurological and clinical assessments were done every 3 months, and brain magnetic resonance imaging was performed at baseline and the end of the study. RESULTS: The cumulative probability of developing clinically definite multiple sclerosis was significantly lower in the IVIg treatment group compared with the placebo group (rate ratio, 0.36 [95% confidence interval, 0.15-0.88]; P = .03). Patients in the IVIg treatment group had a significant reduction in the volume and number of T2-weighted lesions and in the volume of gadolinium-enhancing lesions as compared with the placebo group (P = .01, P = .01, and P = .03, respectively). Treatment was well tolerated, compliance was high, and incidence of adverse effects did not differ significantly between groups. CONCLUSIONS: Intravenous immunoglobulin treatment for the first year from onset of the first neurological event suggestive of demyelinative disease significantly lowers the incidence of a second attack and reduces disease activity as measured by brain magnetic resonance imaging.

Screening for early cognitive impairment in multiple sclerosis patients using the clock drawing test.

The clock drawing test (CDT) is a complex task assessing integrative functions, abstract thinking and visuospatial organization. In the present study we evaluated the CDT as a possible screening instrument for early cognitive impairment in multiple sclerosis (MS) patients. In total, 107 MS patients completed the CDT as well as a battery assessing five cognitive domains. There were 73 female and 34 male participants (mean age 45.4+/-11.6 years, range 19-69). The majority (76/107) were diagnosed with a relapsing-remitting disease course. Mean expanded disability status scale (EDSS) score was 4.3+/-2.4 (range 0-8). The CDT was scored on a 1-6 point scale with "1" being a perfect score and "6" reflecting severe disorganization. Mean CDT score was 2.6+/-1.4. In 53% of patients the CDT was normal while in 11.2% dementia was apparent. The CDT score did not correlate with the total EDSS. Significant correlations were obtained with the mental functional system score of the EDSS (r = 0.78; p = 0.0001), visual learning and recall, sustained attention and concentration. Our findings demonstrate the sensitivity of the CDT to several cognitive domains. The absence of correlation with total EDSS score coupled with significant correlation with the mental functional system suggests that the CDT may be useful for screening MS patients.