Measuring disability in relapsing-remitting MS

The ultimate aim of disease-modifying therapy for multiple sclerosis (MS) is to reduce or reverse neurologic disability, but consensus has developed that current treatments may be most effective early in MS, when neurologic disability is minimal. For the early stages of MS—clinically isolated syndromes or relapsing-remitting MS (RRMS)—there is uncertainty and controversy about the best way to measure disease severity and disability. Should we focus on new brain lesions, which can be detected at a frequency up to 10 times greater than clinical relapses? This is appealing, but the correlation between new brain lesions and clinical manifestations has been disappointingly weak.^1,2 Should we count relapses? This is relatively easy to do, but relapses may resolve completely, without leaving any residual disability, and bear an uncertain relationship to future neurologic disability. Should we define disability based on the standard disease severity scale—Kurtzke's³ Expanded Disability Status Scale (EDSS)? In this approach, EDSS worsening that persists on 2 consecutive study visits, separated by 3 or 6 months, is considered confirmed disability progression. However, the mild end of the EDSS scale has been criticized as quantifying neurologic signs and impairment …