Glymphatic dysfunction in multiple sclerosis and its association with disease pathology and disability

Background: MS is a chronic neuroinflammatory and neurodegenerative disease, in which the glymphatic system remains underexplored. The diffusion tensor image analysis along the perivascular space (ALPS) offers a non-invasive method to assess glymphatic function. Objective: To investigate glymphatic function in MS, and its relationship with disease pathology and disability. Methods: This retrospective study involved 118 MS patients, divided based on the Expanded Disability Status Scale (EDSS) into MS-L (EDSS < 3) and MS-H (EDSS ≥ 3). The ALPS index, brain parenchymal fraction (BPF), and lesion load (LL) were measured. Subgroup comparisons, ALPS index correlations with clinical and MRI measures, and logistic regression were performed. Results: Significant differences in the mean ALPS index between MS-H and MS-L (d=-0.71, p-FDR=0.001) were found. The ALPS index correlated significantly with disease duration (rp=-0.29, p-FDR=0.002), and EDSS (rsp=-0.35, p-FDR=0.0002). The ALPS index also showed significant correlations with BPF and LL. The ALPS index and LL were significant predictors of lower disability (ALPS: Odds ratio (OR)=1.77, p=0.04, LL: OR=0.94, p=0.02). Conclusion: Our findings highlight the ALPS index as an imaging biomarker in MS. This suggests the involvement of glymphatic dysfunction in MS pathology and underscores the need for further research to elucidate its role in MS.