Disease evolution in multiple sclerosis

Multiple sclerosis is a long-term disease that evolves over a period of 30 to 40 years with progressive accumulation of unremitting disability. When developing treatments for multiple sclerosis, it is important to be able to measure accurately the impact of treatments on disability progression. An analysis of 31 previous clinical trials revealed that small changes in EDSS scores measured across two or three years may be insufficiently sensitive to detect sustained changes in disability reliably. Information from large longitudinal natural history databases indicates that long-term outcome is largely independent of previous relapse history, although the occurrence of relapses complicates the short-term quantification of unremitting disability. Treatment effects on relapses may thus not predict long-term effects on disability, although currently available data are insufficient to settle this issue. Natural history studies show that the principal determinant of long-term outcome is conversion to a progressive disease course, which may be related to neurodegeneration of specific neuronal pathways, for example the corticospinal tract. For this reason, it is important to develop tools to identify disease conversion that could be used in future clinical trials.