Background and objectives: The dynamics of microstructural spinal cord (SC) damage and repair in people with multiple sclerosis (pwMS) and their clinical relevance have yet to be explored. We set out to describe patient-specific profiles of microstructural SC damage and change during the first year after MS diagnosis and to investigate their associations with disability and SC atrophy at 5 years.

Methods: We performed a longitudinal monocentric cohort study among patients with relapsing-remitting MS: first relapse <1 year, no relapse <1 month, and high initial severity on MRI (>9 T2 lesions on brain MRI and/or initial myelitis). pwMS and age-matched healthy controls (HCs) underwent cervical SC magnetization transfer (MT) imaging at baseline and at 1 year for pwMS. Based on HC data, SC MT ratio z-score maps were computed for each person with MS. An index of microstructural damage was calculated as the proportion of voxels classified as normal at baseline and identified as damaged after 1 year. Similarly, an index of repair was also calculated (voxels classified as damaged at baseline and as normal after 1 year). Linear models including these indices and disability or SC cross-sectional area (CSA) change between baseline and 5 years were implemented.

Results: Thirty-seven patients and 19 HCs were included. We observed considerable variability in the extent of microstructural SC damage at baseline (0%-58% of SC voxels). We also observed considerable variability in damage and repair indices over 1 year (0%-31% and 0%-20%), with 18 patients showing predominance of damage and 18 predominance of repair. The index of microstructural damage was associated positively with the Expanded Disability Status Scale score (r = 0.504, p = 0.002) and negatively with CSA change (r = -0.416, p = 0.02) at 5 years, independent of baseline SC lesion volume.

Discussion: People with early relapsing-remitting MS exhibited heterogeneous profiles of microstructural SC damage and repair. Progression of microstructural damage was associated with disability progression and SC atrophy 5 years later. These results indicate a potential for microstructural repair in the SC to prevent disability progression in pwMS.