No abstract

In childhood and juvenile cases, multiple sclerosis (MS) is associated with cognitive impairment and low IQ scores, the latter related to younger age at onset. These aspects are of critical importance in helping children and adolescents with MS to manage their difficulties and psychosocial challenges.

The Brief Repeatable Battery of Neuropsychological Tests (BRB) is by far the most widely used instrument to estimate cognitive dysfunction in multiple sclerosis (MS) patients. However, the paucity of normative data currently limits its applicability. We administered the BRB to 200 healthy subjects to obtain normative values. Moreover, we assessed the influence of demographic factors on the test scores and calculated corrections for these relevant factors. To test executive functions not explored by the BRB, we also included the Stroop word-color task (ST). Higher educational level was associated with better performance on all the tests, except for the world list generation (WLG) and the ST, considering version A, and on Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT) and Selective Reminding Test-Delayed (SRT-D), considering version B. Females performed better than males on the WLG considering version A, and on the SRT-Long-Term Storage (SRT-LTS) and SRT-Consistent Long-Term Retrieval (SRT-CLTR) considering version B. Increasing age was associated with worse performance on the ST in version A, and on the SRT-LTS, SRT-CLTR and WLG in version B. Our data can improve the applicability of the BRB for both clinical and research purposes.

Our findings confirm the importance of systematic assessment of cognitive and psychosocial issues in children and teens with MS. The progressive nature of the cognitive difficulties emphasizes the need for developing effective treatment strategies.

Cortical atrophy was found only in cognitively impaired patients and was significantly correlated with a poorer performance on tests of verbal memory, attention/concentration, and verbal fluency. Gray matter pathology may contribute to the development of cognitive impairment in MS from the earliest stages of the disease.

Objective:To investigate the impact of interferon-beta (IFN␤) on disease progression in relapsing-remitting multiple sclerosis patients. Methods: A cohort of 1,504 relapsing-remitting multiple sclerosis (1,103 IFN␤-treated and 401 untreated) patients was followed for up to 7 years. Cox proportional hazards regression adjusted for propensity score inverse weighting was used to assess the differences between the two groups for three different clinical end points: secondary progression (SP) and irreversible Expanded Disability Status Scale (EDSS) scores 4 and 6. Times from first visit and from date of birth were used as survival time variables. Results: The IFN␤-treated group showed a highly significant reduction in the incidence of SP (hazard ratio [HR], 0.38, 95% confidence interval [CI], 0.24 -0.58 for time from 1st visit; HR, 0.36, 95% CI, 0.23-0.56 for time from date of birth; p Ͻ 0.0001), EDSS score of 4 (HR, 0.70, 95% CI, 0.53-0.94 for time from first visit; HR, 0.69, 95% CI, 0.52-0.93 for time from date of birth; p Ͻ 0.02), and EDSS score of 6 (HR, 0.60, 95% CI, 0.38 -0.95 for time from first visit; HR, 0.54, 95% CI, 0.34 -0.86 for time from date of birth; p Յ 0.03) when compared with untreated patients. SP and EDSS scores of 4 and 6 were reached with significant delays estimated by times from first visit (3.8, 1.7, and 2.2 years) and from date of birth (8.7, 4.6, and 11.7 years) in favor of treated patients. Sensitivity analysis confirmed findings. Interpretation: IFN-␤ slows progression in relapsing-remitting multiple sclerosis patients.Ann Neurol 2007;61: 300 -306 Few experienced in the long-term management of multiple sclerosis (MS) patients would disagree that the development of unremitting disability progression represents the major adverse event in the course of this illness, and as a consequence, it is the most important target for clinical trials to evaluate their real cost effectiveness. Whether long-term treatment with the current interferon-␤ (IFN␤) products in relapsingremitting MS (RRMS) can alter the development of long-term disability is not yet known, but it can be surmised from short-term randomized controlled trials (RCTs) 1-3 and their continuous extensions at no more than 4 years 4 and 5 years. 5 This is the stage at which immunomodulatory therapy is likely to be most effective, but then the long-term benefits on disability have to be projected from the results generated during a much earlier and briefer period in the natural disease course. Long-term RCTs would undoubtedly provide definitive evidence, but they are impractical and considered by many to be unethical. 6 More recently, further data have been collected in noncontinuous and/or retrospective, open-label extensions of the IFN␤ RCTs 7-10 ; but in these studies, the protection against bias afforded by randomization was largely lost.11 Moreover, patients enrolled in the placebo arms of RCTs do not represent the natural history of MS because they are selected for having frequent attacks during a set interval before the study....

Over a 3-year period cognitive deterioration can be expected in approximately one-third of MS patients with relatively short disease duration. The SDMT is particularly suitable for longitudinal assessment of MS-related cognitive changes.

Background : We previously reported selective decreases of neocortical volumes in patients with early relapsing-remitting (RR) multiple sclerosis (MS) with mild cognitive impairment, with a good correlation between cortical volumes and cognitive measures.Objective: To assess the relevance of gray matter changes over time to changes in cognition in RRMS.Design: A longitudinal survey after 2.5 years. Each patient underwent a magnetic resonance imaging (MRI) protocol identical to that performed at baseline; cognitive performance was reassessed with the Rao Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis. Setting: Two university MS clinics.Patients: Of 41 patients with RRMS who participated in the original cross-sectional study, 28 were available for the follow-up evaluation (18 women; mean±SD age, 37.1±8.9 years; mean±SD MS duration, 7.3±2.9 years; mean±SD Expanded Disability Status Scale score, 1.8±1.5). Main Outcome Measures:We measured the percentage of brain volume changes, normalized cortical volume (NCV) changes, and normalized deep gray matter volume changes on conventional T1-weighted MRIs and changes in lesion load on T2-weighted MRIs. The number of tests failed on the Rao Brief Repeatable Battery were used to classify the patients as cognitively deteriorating or stable or improving.Results: We identified 12 of 28 cognitively deteriorating and 16 of 28 stable or improving patients. These subgroups did not differ in the mean±SD percentage of brain volume changes (−2.1%±1.2% vs −1.3%±1.3%; P=.11), normalized deep gray matter volume changes (−2.1±2.8 mL vs −0.6±3.1 mL; P=.60), and changes in lesion load on T2-weighted MRIs (1.9±2.6 mL vs 1.6±2.3 mL; P=.73). However, NCV changes were significantly higher in deteriorating than in stable or improving patients (−43.0±18.9 mL vs −17.8 ± 26.6 mL; P = .007). In deteriorating patients, NCV changes were correlated with performance in a verbal fluency test (r=0.73; PϽ.001). In a regression model, only NCV changes were significantly associated with deteriorating cognitive performance (odds ratio, 0.8; 95% confidence interval, 0.7-0.9). Conclusion:Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.