Introduction: Despite the major prognostic value of early spinal cord (SC) damage in MS, the processes of demyelination and remyelination in this structure and their clinical relevance remain to be evaluated. In this longitudinal study, we used magnetization transfer ratio (MTR) changes in the cervical SC to generate patient-specific profiles of myelin content change and investigated their clinical relevance. Objectives/Aims: i) to characterise myelin content changes in the SC over a period of 1 year in early relapsing-remitting MS patients (RRMS); ii) to investigate the association between SC myelin content changes with disability and cross-sectional area (CSA) at 5-year. Methods: After IRB approval (NCT02117375), 37 RRMS patients (disease duration<1 year; mean EDSS=0.6 at baseline [BL]) underwent a cervical SC MRI at BL, 1 year and 5 years, and 19 healthy controls (HC) at BL only. SC lesions were manually segmented on T2*w cervical axial images at BL. CSA in C2C3 was computed at BL and 5 years on T1w brain images. Based on MTR maps of HC, SC MTR z-maps were computed for each MS patient at BL and 1 year and binarized at -2.58 (p=.01) as a proxy of demyelination. A global index of myelin content change (GIMCC) was calculated as the proportion of voxels classified as normal at BL and identified as demyelinated after 1 year (demyelination over time) minus the proportion of voxels classified as demyelinated at BL but not at 1 year (remyelination over time). Partial correlations between GIMCC and disability scores or CSA at BL and 5 years were calculated, with age and gender as covariates. Results: We observed a wide variability of GIMCC (from -13% to 28%), with 18 patients showing a predominance of demyelination over 1 year (GIMCC>0) and 18 a predominance of remyelination (GIMCC<0). Greater GIMCC, reflecting a predominant process of demyelination over remyelination in the SC, was associated with more severe disability at 5 years (EDSS p=.007) and with greater disability progression over the follow-up (EDSS change over 5 years p=.012). Greater GIMCC was associated with reduced CSA at 5 years (p=.032) and BL (p=.023), but not with lesion volume at BL (p=.36). Conclusion: Patients with early RRMS exhibit heterogeneous profiles of SC myelin loss and repair measured over a period of one year. Greater SC remyelination during the first year was significantly associated with lower disability progression and greater SC volume 5 years later. These results highlight the potential of myelin repair in the SC to prevent neurodegeneration and clinical progression in patients with MS.