BACKGROUND: We explored the evolution of brain atrophy in relation to development of confirmed disability progression (CDP) on serial 1.5T magnetic resonance imaging (MRI) scans over a 10-year period in 181 patients with early relapsing-remitting multiple sclerosis (RRMS). METHODS: At 10-year follow-up, they were divided into those with (100) or without (76) CDP (confirmed after 48 weeks). Changes in whole brain (WB), cortical, gray matter (GM), white matter, and ventricular cerebrospinal fluid (vCSF) volumes were calculated on three-dimensional T1-weighted (3D-T1) scans between all available time points. RESULTS: In multiple sclerosis (MS) patients with CDP compared to those without, the greatest effect size percentage volume change from baseline to follow-up was detected for WB (d = 0.55, -7.5% vs -5.2%, p < 0.001), followed by vCSF (d = 0.51, +41.1% vs +25.7%, p < 0.001), cortical (d = 0.49, -7.7% vs -6.2%, p = 0.001), and GM (d = 0.40, -7.1% vs -5.8%, p = 0.006) volumes. Mixed-effects model analysis, adjusted for age, sex, and treatment change, showed significant interactions between CDP status and percentage changes for WB and vCSF (p < 0.001), cortical (p = 0.02), and GM (p = 0.04) volumes. CONCLUSIONS: WB and cortical atrophy, and enlargement of vCSF spaces are associated with development of CDP on serial yearly MRI assessments over a period of 10 years.

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo The State University of New York Buffalo NY USA

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo The State University of New York Buffalo NY USA Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine and General University Hospital Charles University Prague Prague Czech Republic

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo The State University of New York Buffalo NY USA IRCCS S Maria Nascente Don Carlo Gnocchi Foundation Milan Italy

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo The State University of New York Buffalo NY USA MR Imaging Clinical Translational Research Center Jacobs School of Medicine and Biomedical Sciences University at Buffalo The State University of New York Buffalo NY USA

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine and General University Hospital Charles University Prague Prague Czech Republic

Department of Radiology 1st Faculty of Medicine and General University Hospital Charles University Prague Prague Czech Republic

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