Subjective sleep disturbances are associated with reduced MRI-derived perivascular-space diffusivity in multiple sclerosis

Background and objective: Sleep modulates brain-fluid transport and glymphatic clearance. In multiple sclerosis (MS), lower diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index has been reported, but whether sleep quality contributes to DTI-ALPS variability is unknown. We assessed whether sleep disturbances are associated with a lower DTI-ALPS index in MS. Methods: 77 MS patients and 84 age- and sex-matched healthy controls (HC) underwent 3 T brain MRI. In MS patients, disability was assessed with the expanded disability status scale (EDSS), sleep quality with the Pittsburgh sleep quality index (PSQI; >5 defining sleep disturbances), and fatigue with the modified fatigue impact scale (MFIS). DTI-ALPS index was derived from fractional anisotropy (FA) maps after lesion exclusion. Results: Sleep disturbances were reported in 32 (41.6%) MS patients. Disease duration, clinical phenotype, treatment status, and EDSS score did not differ between patients with and without sleep disturbances (p ≥ 0.181). Compared with HC, both MS groups showed a higher T2-hyperintense lesion volume, a lower brain volume, a lower FA and a higher mean diffusivity in normal-appearing white matter, and a lower DTI-ALPS index (p-FDR≤0.007). DTI-ALPS index was lower in patients with sleep disturbances than those without (p-FDR=0.029), with no differences in other MRI variables. In MS patients, a higher PSQI score was associated with a lower DTI-ALPS index (r=−0.356, p-FDR=0.003) and a higher MFIS score (r=0.461, p-FDR<0.001), but not with conventional MRI measures (p-FDR≥0.189). Conclusions: Sleep disturbances are associated with reduced MRI-derived perivascular-space diffusivity in MS, independent of clinical disability and conventional MRI measures. Sleep quality should be considered when interpreting DTI-ALPS measures in MS.