Redefining the role of the cerebellum in restless legs syndrome

Objectives: We aimed to investigate alterations in cerebellar volume and the intrinsic cerebellar network in patients with restless legs syndrome (RLS).Methods: We recruited 69 patients with RLS and 50 healthy controls who underwent brain magnetic resonance imaging (MRI), including three-dimensional T1-weighted imaging. The total cerebellar volume and cerebellar volume subdivisions were analyzed through automatic cerebellum anatomical parcellation using U-Net with locally constrained optimization program. The intrinsic cerebellar network was calculated through brain analysis using a graph theory program based on the cerebellar volume subdivisions. The cerebellar volumes and intrinsic cerebellar networks were compared between patients with RLS and healthy controls.Results: The cerebellar volume and subdivisions in patients with RLS did not show significant differences compared to those in healthy controls. However, significant alterations were observed in the intrinsic cerebellar network of patients with RLS. Increased mean clustering coefficient (0.185 vs. 0.114; p = 0.047) and smallworldness index (0.927 vs. 0.800; p = 0.047) were observed in patients with RLS. Additionally, total cerebellar volume was negatively correlated with the Pittsburgh Sleep Quality Index (r = -0.398; p = 0.020) and Insomnia Severity Index (ISI; r = -0.396; p = 0.011). Negative correlations were additionally observed between the right X lobule volume and the International Restless Legs Syndrome Severity Scale (r = -0.425; p = 0.008) and between the vermis VIII volume and ISI score (r = -0.399; p = 0.011).Conclusion: We demonstrated alterations in the intrinsic cerebellar network in patients with RLS compared with healthy controls, showing increased connectivity with increased segregation in patients with RLS. This suggests a potential role of the cerebellum in RLS pathophysiology.