CNS Atrophy Predicts Future Dynamics of Disability Progression in a Real-World Multiple Sclerosis Cohort.

Abstract

BACKGROUND\nIn an era of individualized multiple sclerosis (MS) patient management, biomarkers for accurate prediction of future clinical outcomes are needed. We aimed to evaluate the potential of short-term MRI atrophy measures and serum neurofilament light chain (sNfL) as predictors of the dynamics of disability accumulation in relapse-onset MS.\n\n\nMETHODS\nBrain gray and white matter, thalamic, striatal, pallidal, cervical spinal cord volumes and lesion-load were measured over three available time points (mean time-span: 2.24±0.70 years) for 183 patients (140 relapsing-remitting (RRMS) and 43 secondary-progressive (SPMS); 123 female, age: 46.4±11.0 years; disease duration: 15.7±9.3 years) and their respective annual changes were calculated. Baseline sNfL was also measured in the third available time-point for each patient. Subsequently, patients received annual clinical examinations over 5.4±3.7 years including expanded disability status scale (EDSS), nine-hole peg test and timed 25-foot walk test.\n\n\nRESULTS\nHigher annual spinal cord atrophy rates and lesion-load increase predicted higher future expanded disability status scale worsening over time in SPMS. Lower baseline thalamic volumes predicted higher walking-speed worsening over time in RRMS. Lower baseline gray matter as well as higher white matter and spinal cord atrophy rates, lesion-load increase, baseline striatal volumes and baseline sNfL predicted higher future hand-dexterity worsening over time. All models showed reasonable to high prediction accuracy.\n\n\nCONCLUSION\nThis study demonstrates the capability of short-term MRI metrics to accurately predict future dynamics of disability progression in a real-world relapse-onset MS cohort. The current work represents a step towards the utilization of structural MRI-measurements in patient care.