Sodium in the Relapsing–Remitting Multiple Sclerosis Spinal Cord: Increased Concentrations and Associations With Microstructural Tissue Anisotropy

Background: Associations between brain total sodium concentration, disability, and disease progression have recently been reported in multiple sclerosis. However, such measures in spinal cord have not been reported. Purpose: To measure total sodium concentration (TSC) alterations in the cervical spinal cord of people with relapsing–remitting multiple sclerosis (RRMS) and a control cohort using sodium MR spectroscopy (MRS). Study Type: Retrospective cohort. Subjects: Nineteen people with RRMS and 21 healthy controls. Field Strength/Sequence: 3 T sodium MRS, diffusion tensor imaging, and 3D gradient echo. Assessment: Quantification of total sodium concentration in the cervical cord using a reference phantom. Measures of spinal cord cross-sectional area, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity from 1H MRI. Clinical assessments of 9-Hole Peg Test, 25-Foot Timed walk test, Paced Auditory Serial Addition Test with 3-second intervals, grip strength, vibration sensitivity, and posturography were performed on the RRMS cohort as well as reporting lesions in the C2/3 area. Statistical Tests: Multiple linear regression models were run between sodium and clinical scores, cross-sectional area, and diffusion metrics to establish any correlations. Results: A significant increase in spinal cord total sodium concentration was found in people with RRMS relative to healthy controls (57.6 ± 18 mmol and 38.0 ± 8.6 mmol, respectively, P < 0.001). Increased TSC correlated with reduced fractional anisotropy (P = 0.034) and clinically with decreased mediolateral stability assessed with posturography (P = 0.045). Data Conclusion: Total sodium concentration in the cervical spinal cord is elevated in RRMS. This alteration is associated with reduced fractional anisotropy, which may be due to changes in tissue microstructure and, hence, in the integrity of spinal cord tissue. Level of Evidence: 1. Technical Efficacy Stage: 2.