White matter microstructure alterations in idiopathic restless legs syndrome: a study combining crossing fiber-based and tensor-based approaches

Introduction: Restless legs syndrome (RLS) is a common sensorimotor disorder characterized by an irrepressible urge to move the legs and frequently accompanied by unpleasant sensations in the legs. The pathophysiological mechanisms underlying RLS remain unclear, and RLS is hypothesized to be associated with alterations in white matter tracts. Methods: Diffusion MRI is a unique noninvasive method widely used to study white matter tracts in the human brain. Thus, diffusion-weighted images were acquired from 18 idiopathic RLS patients and 31 age- and sex-matched healthy controls (HCs). Whole brain tract-based spatial statistics (TBSS) and atlas-based analyzes combining crossing fiber-based metrics and tensor-based metrics were performed to investigate the white matter patterns in individuals with RLS. Results: TBSS analysis revealed significantly higher fractional anisotropy (FA) and partial volume fraction of primary (F1) fiber populations in multiple tracts associated with the sensorimotor network in patients with RLS than in HCs. In the atlas based analysis, the bilateral anterior thalamus radiation, bilateral corticospinal tract, bilateral inferior fronto-occipital fasciculus, left hippocampal cingulum, left inferior longitudinal fasciculus, and left uncinate fasciculus showed significantl increased F1, but only the left hippocampal cingulum showed significantly higher FA. Discussion: The results demonstrated that F1 identified extensive alterations in white matter tracts compared with FA and confirmed the hypothesis that crossing fiber-based metrics are more sensitive than tensor-based metrics in detecting white matter abnormalities in RLS. The present findings provide evidence that the increased F1 metric observed in sensorimotor tracts may be a critical neural substrate of RLS, enhancing our understanding of the underlying pathological changes.