Researchers at University of Bologna, Italy, evaluated medial thalamus metabolism and structural integrity in 23 patients with restless legs syndrome and 19 healthy controls. Proton magnetic resonance spectroscopy (PMRS) disclosed a significantly reduced N-acetylaspartate creatine ratio and N-acetylaspartate concentrations in the medial thalamus of patients with restless legs syndrome compared to controls (P<0.01). Lower N-acetylaspartate concentrations were significantly associated with a family history of restless legs syndrome (P=0.018). Dysfunction of the medial thalamus and limbic system plays a role in the pathophysiology of idiopathic restless legs syndrome. In contrast, thalamic volume studies using diffusion tensor imaging, and voxel-based morphometry showed no structural thalamic changes. 
COMMENT. RLS is heterogeneous, some cases symptomatic of iron deficiency, uremia, pregnancy and polyneuropathy, and others idiopathic, especially patients with onset before age 30 years. Genetic risk variants have also been identified. 
Investigation of unmedicated early onset restless legs syndrome by voxel-based morphometry, T2 relaxometry, and functional MR imaging during the night-time hours reveals no regional brain volume changes but indicates increased iron content in the globus pallidus and substantia nigra, suggesting dysfunction of the basal ganglia. Activation of the striatofrontolimbic area may represent the neurofunctional substrate mediating RLS.