Defining the clinical course of multiple sclerosis: the 2013 revisions

Abstract

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.

Figure 1. The 1996 vs 2013 multiple sclerosis phenotype descriptions for relapsing disease

*Activity determined by clinical relapses and/or MRI activity (contrast-enhancing lesions; new or unequivocally enlarging T2 lesions assessed at least annually); if assessments are not available, activity is “indeterminate.” **CIS, if subsequently clinically active and fulfilling current multiple sclerosis (MS) diagnostic criteria, becomes relapsing-remitting MS (RRMS).

Figure 2. The 1996 vs 2013 multiple sclerosis phenotype descriptions for progressive disease

*Activity determined by clinical relapses assessed at least annually and/or MRI activity (contrast-enhancing lesions; new and unequivocally enlarging T2 lesions). **Progression measured by clinical evaluation, assessed at least annually. If assessments are not available, activity and progression are “indeterminate.” MS = multiple sclerosis; PP = primary progressive; PR = progressive relapsing; SP = secondary progressive.