Alterations in glymphatic system-related MRI markers in patients with primary restless legs syndrome and association with disease severity.

BACKGROUND AND OBJECTIVE: Restless legs syndrome (RLS) is a sleep-related sensorimotor disorder characterized by a prominent circadian rhythm that severely impairs patients' quality of life and sleep. Although previous studies indicate that sleep disturbances can disrupt glymphatic function, alterations in glymphatic system-related MRI markers in patients with primary RLS remain to be fully clarified. This study aims to systematically evaluate alterations in multimodal glymphatic system-related MRI markers in patients with primary RLS and to explore their clinical relationships with disease severity. METHODS: This prospective study enrolled 42 patients with primary RLS and 42 healthy controls (HC) with comparable age and sex distributions. All participants underwent multi-sequence brain MRI and clinical sleep quality questionnaire assessments. Glymphatic system-related MRI parameters, including the choroid plexus volume fraction (CPVF), perivascular space volume fraction (PVSVF), diffusion tensor imaging along the perivascular space (DTI-ALPS) index, and free water in white matter (FW-WM) volume fraction, were quantified. Partial correlation analysis was performed to evaluate relationships between these MRI parameters and clinical characteristics of RLS. RESULTS: Compared with HC, the RLS group demonstrated a significantly decreased DTI-ALPS index (1.440 ± 0.078 vs. 1.629 ± 0.086, PFDR-corrected < 0.001), along with significantly increased FW-WM (0.211 ± 0.029 vs. 0.189 ± 0.017, PFDR-corrected < 0.001) and CPVF (0.925 ± 0.277 vs. 0.747 ± 0.253, PFDR-corrected = 0.007). No statistically significant difference was observed in PVSVF (PFDR-corrected = 0.367). Partial correlation analysis revealed that the FW-WM in patients with RLS was significantly positively correlated with International Restless Legs Syndrome Study Group Rating Scale (IRLS) scores (r = 0.491, PFDR-corrected = 0.009); no other clinical or imaging parameters demonstrated significant correlations (all PFDR-corrected > 0.05). CONCLUSION: Patients with primary RLS exhibit alterations in glymphatic system-related MRI markers, with FW-WM correlated with disease severity. These findings suggest that these MRI parameters represent candidate surrogate markers for RLS. However, longitudinal studies are required to establish whether these alterations are causes, consequences, or correlates of RLS severity.