Small vessel disease in patients with restless legs syndrome evidenced by elevated peak width of skeletonized mean diffusivity

Abstract

Peak width of skeletonized mean diffusivity (PSMD) is a novel marker of small vessel disease. This study aimed to investigate small vessel disease in patients with restless legs syndrome (RLS) using PSMD. We prospectively enrolled 65 patients with primary RLS and 59 age- and sex-matched healthy controls. Diffusion tensor imaging (DTI) was performed using a 3-T magnetic resonance imaging scanner in patients with RLS and healthy controls. We obtained PSMD by DTI in several steps, including preprocessing, skeletonization, application of a custom mask, and histogram analysis. We compared the PSMD between patients with RLS and healthy controls and performed a correlation analysis between the PSMD and clinical characteristics in patients with RLS. The PSMD significantly differed between patients with RLS and healthy controls; it was higher in patients with RLS than that in healthy controls (2.423 vs. 2.298 × 10⁻⁴ mm²/s, p = 0.017). The PSMD significantly differed according to the RLS severity (2.305 × 10⁻⁴ mm²/s, moderate RLS; 2.368 × 10⁻⁴ mm²/s, severe RLS; 2.477 × 10⁻⁴ mm²/s, very severe RLS; p = 0.003). Additionally, the PSMD was positively correlated with age (r = 0.522, p < 0.001) and RLS severity (r = 0.263, p = 0.033). Patients with RLS exhibited a higher PSMD than that in healthy controls, indicating the evidence of small-vessel disease in RLS and that the severity increased as RLS severity increased. These findings provide crucial information for clinical management and treatment strategies, highlighting the importance of addressing small vessel disease in patients with RLS.