Restless legs syndrome (RLS) as a sleep/wake cycle disorder has a circadian rhythm that affects patients in the evening or at night. Periodic limb movements in sleep (PLMS) occur in up to 85% of patients with RLS, are currently the only objective measure of RLS, and build a prominent cause of sleep disruption. There are some reports in which the onset of RLS or PLMS coincided with a documented structural lesion (e.g. stroke). PLMS onset after stroke was observed in the internal capsule, cerebellum, corona radiata, and pons. Special neuroimaging studies assessed the involvement of cortical and subcortical structures, respectively gray and white matter, in RLS. Diffusion tensor imaging (DTI) and additional findings of a combined post-mortem and voxel-based morphometry (VBM) study point to a possible wide-spread subcortical involvement of white matter areas; however, the relevance of these alterations is open as they may also mirror secondary changes in RLS.