Emerging therapies for treatment of multiple sclerosis

In the last decade, a new armamentarium of immune-based therapies have been developed and tested in patients with multiple sclerosis. Some of these therapies are showing a high level of efficacy, with an acceptable adverse effect profile. Because present therapies have significant limitations in slowing disease progression, require injections, are sometimes associated with significant side effects of immunosuppression, and do little to reverse disability, identifying more effective treatments is an important goal for clinical research in multiple sclerosis. However, in order to improve our current approach to disease-modifying therapies, it is imperative to promote the development of individualized therapy strategies

The effects of test-enhanced learning on long-term retention in AAN annual meeting courses.

OBJECTIVE: We measured the long-term retention of knowledge gained through selected American Academy of Neurology annual meeting courses and compared the effects of repeated quizzing (known as test-enhanced learning) and repeated studying on that retention. METHODS: Participants were recruited from 4 annual meeting courses. All participants took a pretest. This randomized, controlled trial utilized a within-subjects design in which each participant experienced 3 different postcourse activities with each activity performed on different material. Each key information point from the course was randomized in a counterbalanced fashion among participants to one of the 3 activities: repeated short-answer quizzing, repeated studying, and no further exposure to the materials. A final test covering all information points from the course was taken 5.5 months after the course. RESULTS: Thirty-five participants across the 4 courses completed the study. Average score on the pretest was 36%. Performance on the final test showed that repeated quizzing led to significantly greater long-term retention relative to both repeated studying (55% vs 46%; t[34] = 3.28, SEM = 0.03, p = 0.01, d = 0.49) and no further exposure (55% vs 44%; t[34] = 3.16, SEM = 0.03, p = 0.01, d = 0.58). Relative to the pretest baseline, repeated quizzing helped participants to retain almost twice as much of the knowledge acquired from the course compared to repeated studying or no further exposure. CONCLUSIONS: Whereas annual meeting continuing medical education (CME) courses lead to long-term gains in knowledge, when repeated quizzing is added, retention is significantly increased. CME planners may consider adding repeated quizzing to increase the impact of their courses

Adjustments in Torque Steadiness During Fatiguing Contractions Are Inversely Correlated With IQ in Persons With Multiple Sclerosis

Fatigue is one of the most debilitating symptoms of multiple sclerosis (MS), and the underlying mechanisms are poorly understood. When exposed to a physical or cognitive challenge, individuals with MS tend to exhibit greater declines in task performance (performance fatigability) and increased levels of self-reported fatigue (perceived fatigability), but these effects may be attenuated by greater intellectual capacity. The purpose of our study was to examine the influence of intelligence on fatigability in persons with MS. We hypothesized that greater intellectual capacity confers some protection against heightened levels of fatigue and fatigability associated with MS. Twelve adults with relapsing-remitting MS were compared with 12 control (CO) subjects who were matched for age, sex, and premorbid intellectual capacity. Performance fatigability was measured as the decline in maximal voluntary contraction (MVC) torque after 60 isometric contractions (10 s contraction at 25% MVC, 5 s rest) performed with the knee extensor muscles. Perceived fatigability was assessed with the modified fatigue impact scale (MFIS) questionnaire (trait fatigability) and the Borg rating of perceived exertion (RPE, state fatigability). Persons with MS reported greater MFIS scores (MS: 43 ± 14; CO: 11 ± 8, P ≤ 0.001). Initial MVC torque for the knee extensors did not differ between the groups (MS: 112 ± 38 N⋅m; CO: 107 ± 44 N⋅m) and the decline (performance fatigability) was similar for both groups (MS: -16 ± 19 N⋅m; CO: -13 ± 16 N⋅m). RPE increased during the fatiguing contraction for both groups (P < 0.001) but was significantly greater in magnitude (main effect for group, P = 0.03) and increased more for the MS group (group × time interaction, P = 0.05). Torque steadiness declined during the fatiguing contractions (main effect for time, P = 0.05) and was less steady for the MS group (main effect for group, P = 0.02). Performance and full-4 IQ was correlated with the decline in torque steadiness for the MS group (r = -0.63, P < 0.05; r = -0.64, P < 0.05). Intellectual capacity was not associated with fatigability in persons with MS but was associated with adjustments in muscle activation during the fatiguing contractions

The nature of verbal memory impairment in multiple sclerosis: A list-learning and meta-analytic study

Abstract The primary purpose of this study was to test the hypothesis that multiple sclerosis (MS) patients have impaired acquisition rather than a retrieval deficit. Verbal memory impairment in MS was examined in 53 relapsing-remitting MS patients and 31 healthy controls (HC), and in a meta-analysis of studies that examined memory functioning in MS with list-learning tasks. The MS group demonstrated significantly lower acquisition and delayed recall performance than the HC group, and the meta-analysis revealed that the largest effect sizes were obtained for acquisition measures relative to delayed recall and recognition. Our data argue against a retrieval deficit as the sole explanation for verbal memory impairment in MS, and make a consistent case for the position that deficient acquisition contributes to the memory dysfunction of MS patients. Deficient acquisition may result from demyelination in relevant white matter tracts that reduces encoding efficiency as a result of impaired speed of information processing. (JINS, 2013, 19, 995-1008) Copyright © INS. Published by Cambridge University Press, 2013

Epstein-Barr virus is present in the brain of most cases of multiple sclerosis and may engage more than just B cells

<div><p>Multiple sclerosis (MS) is a chronic neuroinflammatory condition of the central nervous system (CNS). It is a major cause of neurological disability in young adults, particularly women. What triggers the destruction of myelin sheaths covering nerve fibres is unknown. Both genetic and infectious agents have been implicated. Of the infectious agents, Epstein-Barr virus (EBV), a common herpesvirus, has the strongest epidemiological and serological evidence. However, the presence of EBV in the CNS and demonstration of the underlying mechanism(s) linking EBV to the pathogenesis of MS remain to be elucidated. We aimed at understanding the contribution of EBV infection in the pathology of MS. We examined 1055 specimens (440 DNA samples and 615 brain tissues) from 101 MS and 21 non-MS cases for the presence of EBV using PCR and EBER-<i>in situ</i> hybridization (EBER-ISH). EBV was detected by PCR and/or EBER-ISH in 91/101 (90%) of MS cases compared to only 5/21 (24%) of non-MS cases with other neuropathologies. None of the samples were PCR positive for other common herpesviruses (HSV-1, CMV, HHV-6). By quantitative PCR, EBV viral load in MS brain was mainly low to moderate in most cases. However, in 18/101 (18%) of MS cases, widespread but scattered presence of EBV infected cells was noted in the affected tissues by EBER-ISH. Immunohistochemical analysis of EBV gene expression in the 18 heavily infected cases, revealed that the EBV latent protein EBNA1, and to a lesser extent the early lytic protein BZLF1 were expressed. Furthermore, using double-staining we show for the first time that astrocytes and microglia, in addition to B-cells can also be infected. To the best of our knowledge, this is the most comprehensive study demonstrating that EBV is present and transcriptionally active in the brain of most cases of MS and supports a role for the virus in MS pathogenesis. Further studies are required to address the mechanism of EBV involvement in MS pathology.</p></div