Glymphatic system dysfunction in restless legs syndrome: evidenced by diffusion tensor imaging along the perivascular space

Study Objectives There is growing evidence pointing at glymphatic system dysfunction in diseases with circadian disruption, such as sleep disorders. Lower diffusivity in the direction of perivascular space has been shown in several neurological and sleep-related disorders; however, its role in restless legs syndrome (RLS) is unclear. We hypothesized that similarly, in RLS the diffusivity in glymphatic system is decreased. Here, we aimed to evaluate glymphatic system functionality in patients with RLS, compare it to healthy controls, and analyze the correlation between its function and clinical characteristics.Methods Sixty-nine patients with primary RLS and 51 healthy controls were recruited at a tertiary hospital. All participants underwent diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI) using a 3T MRI scanner, and the DTI along the perivascular space (DTI-ALPS) index was calculated using DTI data. We compared the DTI-ALPS index between the patients with RLS and healthy controls. We also conducted the correlation analysis between the DTI-ALPS index and clinical characteristics, including age, age of onset, symptom duration, and RLS severity.Results DTI-ALPS index differed significantly between the patients with RLS and healthy controls; the DTI-ALPS index in the patients with RLS was lower than that in the healthy controls (1.48 vs. 0.60, p = 0.008). There was no significant correlation between the DTI-ALPS index and clinical characteristics.Conclusion A significantly lower DTI-ALPS index in patients with RLS suggests that the glymphatic system function is impaired in patients with RLS. Graphical Abstract