Atrophy patterns and imaging biomarkers in Indian patients with early relapsing remitting multiple sclerosis: addressing geographic gaps

Abstract Background Gray matter (GM) atrophy in early relapsing–remitting multiple sclerosis (RRMS) is increasingly recognized as a marker of clinical disability yet remains under-characterized in Indian cohorts. We aimed to elucidate patterns of brain atrophy and asymmetry in early RRMS, and to explore its clinical correlates. Methods This cross-sectional case–control study included 50 RRMS patients with EDSS (Expanded Disability Status Score) between 0 and 5, disease duration < 5 years and stable disease course, and 50 age- and sex- matched healthy controls. Participants underwent 3 T MRI, and segmentation was performed using VolBrain to obtain volumetric measures for 231 brain regions. Asymmetry indices (AI) were computed, and statistical analyses were conducted to assess volumetric and AI differences and the correlations of brain volumes with EDSS scores and T2 lesion volumes. Results Despite low clinical disability, short disease duration and stable course, patients showed significant and widespread atrophy affecting global brain tissue and subcortical gray matter, and to a lesser extent cortical gray matter regions and infratentorial structures. Cortical gray matter atrophy was predominantly observed in frontal and temporal regions. Volume loss of the middle frontal gyrus and lateral orbital gyrus demonstrated stronger associations with clinical disability compared to T2 lesion volumes, suggesting their potential role as early imaging biomarkers of disease burden. Conclusion This study identifies clinically linked neuroanatomic targets in early RRMS, supporting volumetric metrics as candidate biomarkers for early prognostication and treatment stratification. The pattern of early subcortical and fronto-temporal cortical involvement observed in our study, warrants further cross-ethnic comparisons, and sets a precedent for future neuroimaging biomarker research in South Asian MS cohorts.