ObjectivesTo assess whether quantitative spinal cord MRI (SC-MRI) measures, including atrophy, and diffusion tensor imaging (DTI) and magnetization transfer imaging metrics were different in radiologically isolated syndrome (RIS) vs healthy controls (HCs).MethodsTwenty-four participants with RIS and 14 HCs underwent cervical SC-MRI on a 3T magnet. Manually segmented regions of interest circumscribing the spinal cord cross-sectional area (SC-CSA) between C3 and C4 were used to extract SC-CSA, fractional anisotropy, mean, perpendicular, and parallel diffusivity (MD, λ⊥, and λ||) and magnetization transfer ratio (MTR). Spinal cord (SC) lesions, SC gray matter (GM), and SC white matter (WM) areas were also manually segmented. Multivariable linear regression was performed to evaluate differences in SC-MRI measures in RIS vs HCs, while controlling for age and sex.ResultsIn this cross-sectional study of participants with RIS, 71% had lesions in the cervical SC. Of quantitative SC-MRI metrics, spinal cord MTR showed a trend toward being lower in RIS vs HCs (p = 0.06), and there was already evidence of brain atrophy (p = 0.05). There were no significant differences in SC-DTI metrics, GM, WM, or CSA between RIS and HCs.ConclusionThe SC demonstrates minimal microstructural changes suggestive of demyelination and inflammation in RIS. These findings are in contrast to established MS and raise the possibility that the SC may play an important role in triggering clinical symptomatology in MS. Prospective follow-up of this cohort will provide additional insights into the role the SC plays in the complex sequence of events related to MS disease initiation and progression.

Background: The spinal cord (SC) is highly relevant to disability in multiple sclerosis (MS), but few studies have evaluated longitudinal changes in quantitative spinal cord magnetic resonance imaging (SC-MRI). Objectives: The aim of this study was to characterize the relationships between 5-year changes in SC-MRI with disability in MS. Methods: In total, 75 MS patients underwent 3 T SC-MRI and clinical assessment (expanded disability status scale (EDSS) and MS functional composite (MSFC)) at baseline, 2 and 5 years. SC-cross-sectional area (CSA) and diffusion-tensor indices (fractional anisotropy (FA), mean, perpendicular, parallel diffusivity (MD, λ⊥, λ||) and magnetization transfer ratio (MTR)) were extracted at C3–C4. Mixed-effects regression incorporating subject-specific slopes assessed longitudinal change in SC-MRI measures. Results: SC-CSA and MTR decreased ( p = 0.009, p = 0.03) over 5.1 years. There were moderate correlations between 2- and 5-year subject-specific slopes of SC-MRI indices and follow-up EDSS scores (Pearson’s r with FA = −0.23 ( p < 0.001); MD = 0.31 ( p < 0.001); λ⊥ = 0.34 ( p < 0.001); λ|| = −0.12 ( p = 0.05), MTR = −0.37 ( p < 0.001); SC-CSA = −0.47 ( p < 0.001) at 5 years); MSFC showed similar trends. The 2- and 5-year subject-specific slopes were robustly correlated ( r = 0.93–0.97 for FA, λ⊥, SC-CSA and MTR, all ps < 0.001). Conclusion: In MS, certain quantitative SC-MRI indices change over 5 years, reflecting ongoing tissue changes. Subject-specific trajectories of SC-MRI index change at 2 and 5 years are strongly correlated and highly relevant to follow-up disability. These findings suggest that individual dynamics of change should be accounted for when interpreting longitudinal SC-MRI measures and that measuring short-term change is predictive of long-term clinical disability.