Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.

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This interventional study provides class 1 evidence that dalfampridine extended-release tablets produce clinically meaningful improvement in walking ability in a subset of people with MS, with the effect maintained between doses.

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Objective: To determine whether glatiramer acetate (GA) slows accumulation of disability in primary progressive multiple sclerosis. Methods: A total of 943 patients with primary progressive multiple sclerosis were randomized to GA or placebo (PBO) in this 3-year, double-blind trial. The primary end point was an intention-to-treat analysis of time to 1-(entry expanded disability status scale, 3.0 -5.0) or 0.5-point expanded disability status scale change (entry expanded disability status scale, 5.5-6.5) sustained for 3 months. The trial was stopped after an interim analysis by an independent data safety monitoring board indicated no discernible treatment effect on the primary outcome. Intention-to-treat analyses of disability and magnetic resonance imaging end points were performed. Results: There was a nonsignificant delay in time to sustained accumulated disability in GA-versus PBO-treated patients (hazard ratio, 0.87 [95% confidence interval, 0.71-1.07]; p ϭ 0.1753), with significant decreases in enhancing lesions in year 1 and smaller increases in T2 lesion volumes in years 2 and 3 versus PBO. Post hoc analysis showed that survival curves for GA-treated male patients diverged early from PBO-treated male subjects (hazard ratio, 0.71 [95% confidence interval, 0.53-0.95]; p ϭ 0.0193). Interpretation:The trial failed to demonstrate a treatment effect of GA on primary progressive multiple sclerosis. Both the unanticipated low event rate and premature discontinuation of study medication decreased the power to detect a treatment effect. Post hoc analysis suggests GA may have slowed clinical progression in male patients who showed more rapid progression when untreated.

IFNbeta-1a demonstrated benefit on MSFC progression, relapses, quality of life, and MRI activity in SPMS.

Strength and motor fatigue can be measured reliably in patients with MS. MS patients experience more fatigue than healthy control subjects during sustained contractions, repetitive contractions, and ambulation. Motor fatigue appears to be distinct from weakness because the degree of fatigue was not associated with the degree of weakness in individual muscles. Quantitative assessment of strength and fatigue may be useful to monitor changes in motor function over time in MS patients.

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