Imaging brain functional and metabolic changes in restless legs syndrome.

Even though the pathophysiology of restless legs syndrome is not completely understood, several imaging studies have contributed to our understanding of the disease. Functional and metabolic impairment seems to be the pathophysiological core, tied to a single brain network or multiple connected brain networks, via neurotransmitter modifications. Positron emission tomography and single photon emission computed tomography studies support a dysfunction of dopaminergic pathways, involving not only the nigrostriatal pathway but also the mesolimbic pathway. Furthermore, a possible role of serotonergic neurotransmission has been suggested. Functional magnetic resonance imaging studies have demonstrated in restless legs syndrome patients a pathologic activation of cerebral areas belonging to both the sensorimotor and the limbic networks. Proton magnetic resonance spectroscopy has confirmed abnormality of the limbic system and suggested the presence of a glutamatergic disorder. Finally magnetic resonance studies using iron-sensitive sequences have demonstrated reduced iron content in several regions of the brain of restless legs syndrome patients. In this review we attempt to integrate all current imaging study results into a convergent pathophysiological interpretation.