Glymphatic system impairment causes clinical disability through the accumulation of tissue damage in multiple sclerosis

Motivation: The role of the glymphatic system in multiple sclerosis (MS)-related disability has not been thoroughly investigated. Diffusion-tensor image analysis along the perivascular space (DTI-ALPS) offers a noninvasive method. Goal(s): To investigate the association between glymphatic function and disability in MS and analyze whether it was mediated by the tissue damage accumulation. Approach: 59 MS patients and 44 healthy controls were enrolled. DTI-ALPS index was calculated. Correlations between DTI-ALPS and tissue damage accumulation and clinical disability were analyzed. Results: The glymphatic system is impaired in MS. The impact of glymphatic impairment on disability is mediated by the tissue damage accumulation. Impact: The impact of glymphatic impairment on disability is mediated by the tissue damage accumulation, indicating a pathological mechanism for MS-related disability.