We investigated the evolution of cortical atrophy in patients with early relapsing-remitting (RR) multiple sclerosis (MS) and its association with lesion volume (LV) accumulation and disability progression. 136 of 181 RRMS patients who participated in the Avonex-Steroids-Azathioprine study were assessed bimonthly for clinical and MRI outcomes over 2 years. MS patients with disease duration (DD) at baseline of ≤24 months were classified in the early group (DD of 1.2 years, ), while patients with DD > 24 months were classified in the late group (DD of 7.1 years, ). Mixed effect model analysis was used to investigate the associations. Significant changes in whole brain volume (WBV) ( ), cortical volume (CV) ( ), and in T2-LV ( ) were detected. No significant MRI percent change differences were detected between early and late DD groups over 2 years, except for increased T2-LV accumulation between baseline and year 2 in the early DD group ( ). No significant associations were found between changes in T2-LV and CV over the followup. Change in CV was related to the disability progression over the 2 years, after adjusting for DD ( ). Significant cortical atrophy, independent of T2-LV accumulation, occurs in early RRMS over 2 years, and it is associated with the disability progression. 1. Introduction Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects both white matter (WM) and gray matter (GM). In the last decade, there has been increased interest in studying GM damage in MS, especially in the cortical regions [1]. Advances in both MRI acquisition and analysis techniques have enabled better detection of changes in GM morphology [2]. The MRI assessments included measurements of cortical atrophy, cortical thinning, and cortical lesions [1–4]. Because imaging techniques are still unable to adequately detect GM lesions, especially in the cortex [5–9], measurement of cortical atrophy is gaining increasing attention in the literature [1], in order to assess the real extent of cortical pathology in vivo in patients with MS [2]. Recent studies have established that subcortical, but not cortical, atrophy is present at the earliest clinical stages of the disease [10–15]. However, most of these studies had a cross-sectional design, and only a few longitudinal studies investigated possible associations between GM atrophy and clinical outcomes in patients with MS [11, 15–18]. In addition, only one serial MRI study investigated the evolution of GM atrophy over a 9-month period [19]. Therefore, one of the main goals of this study
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