Evolution of Brain Volume Loss Rates in Early Stages of Multiple Sclerosis


To describe the dynamics of brain volume loss (BVL) at different stages of relapsing-remitting multiple sclerosis (RRMS), to describe the association between BVL and clinical measures, and to investigate an effect of treatment escalation on the rate of BVL.


Together, 1903 patients predominantly with RRMS from the Avonex-Steroids-Azathioprine cohort (N = 166), the study of early IFN-β1a treatment cohort (N = 180), and the quantitative MRI cohort (N = 1,557) with ≥2 MRI scans and ≥1-year of follow-up were included. Brain MRI scans (N = 7,203) were performed using a single 1.5-T machine. Relationships between age or disease duration and global and tissue-specific BVL rates were analyzed using mixed models.


Age was not associated with the rate of BVL (β = –0.003; Cohen f2 = 0.0005; adjusted p = 0.39). Although disease duration was associated with the rate of BVL, its effect on the BVL rate was minimal (β = –0.012; Cohen f2 = 0.004; adjusted p = 4 x 10–5). Analysis of association between tissue-specific brain volume changes and age (β = –0.019 to –0.011; adjusted p = 0.028–1.00) or disease duration (β = –0.028 to –0.008; adjusted p = 0.16–0.96) confirmed these results. Although increase in the relapse rate (β = 0.10; adjusted p = 9 x 10–9), Expanded Disability Status Scale (EDSS; β = 0.17; adjusted p = 8 x 10–5), and EDSS change (β = 0.15; adjusted p = 2 x 10–5) were associated with accelerated rate of BVL, their effect on the rate of BVL was minimal (all Cohen f2 ≤ 0.007). In 94 patients who escalated therapy, the rate of BVL decreased following treatment escalation by 0.29% (β = –0.29; Cohen f2 = 0.133; p = 5.5 x 10–8).


The rate of BVL is relatively stable throughout the course of RRMS. The accelerated BVL is weakly associated with concurrent higher disease activity, and timely escalation to high-efficacy immunotherapy helps decrease the rate of BVL.

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