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

The role of the glymphatic system in multiple sclerosis (MS)-related disability remains underexplored. Diffusion-tensor image analysis along the perivascular space (DTI-ALPS) offers a non-invasive method to assess glymphatic function.

Objective:

To evaluate glymphatic function in MS patients with lower and higher disability.

Methods:

This study included 118 MS patients who underwent structural, diffusion-weighted imaging, and clinical assessment. The participants were divided into lower (MS-L, n  = 57) and higher disability (MS-H, n  = 61) subgroups. Brain parenchymal fraction (BPF), lesion load (LL), and DTI-ALPS index were measured. Subgroup differences and correlations between DTI-ALPS index and other measures were explored. Logistic regression was performed to evaluate BPF, LL, and DTI-ALPS index in classifying lower and higher disability patients.

Results:

Significant differences in DTI-ALPS index between MS-H and MS-L ( d  = −0.71, false discovery rate-corrected p -value ( p- FDR) = 0.001) were found. The DTI-ALPS index correlated significantly with disease duration ( r _p  = −0.29, p- FDR = 0.002) and EDSS ( r _sp  = −0.35, p- FDR = 0.0002). It also showed significant correlations with BPF and LL. DTI-ALPS index and LL were significant predictors of disability subgroup (DTI-ALPS: odds ratio (OR) = 1.77, p  = 0.04, LL: OR = 0.94, p  = 0.02).

Conclusion:

Our findings highlight DTI-ALPS index as an imaging biomarker in MS, suggesting the involvement of glymphatic impairment in MS pathology, although further research is needed to elucidate its role in contributing to MS-related disability.