Objective: A recent cross-sectional study has shown a plateauing relationship between T2 lesion volume (T2LV) and disability in patients with multiple sclerosis (MS). In this analysis, which also included longitudinal observations, we investigated whether such a relationship is a consequence of the decreased frequency of "inflammatory" events occurring in more disabled patients, rather than reflecting their disability status.

Methods: The placebo arms of 2 clinical trials were analyzed. One cohort consisted of 548 patients with relapsing-remitting (RR) MS enrolled in a 14-month, randomized, double-blind, placebo-controlled trial of oral glatiramer acetate. The second cohort consisted of 358 patients with secondary progressive (SP) MS still experiencing relapses enrolled in a 3-year, randomized, double-blind, placebo-controlled trial of interferon beta-1b.

Results: At baseline, T2LV was associated with disease duration (p < 0.001), age at MS onset (p < 0.001), and disability (p < 0.001). The relationship between baseline T2LV and Expanded Disability Status Scale (EDSS) was not significantly different between patients with RRMS and SPMS. At a multivariate analysis, T2LV change was associated with the number of on-trial relapses (p < 0.001) and age at MS onset (p = 0.02). The correlations of T2LV change with baseline EDSS and EDSS changes were not significant.

Conclusions: We showed that the plateauing relationship between T2 lesion volume and disability in multiple sclerosis is not always present and is likely due to the reduced frequency of "inflammatory" events in the most common form of secondary progressive multiple sclerosis.