Circadian aspects in the pathophysiology of the restless legs syndrome

Several pieces of evidence suggest that a dopaminergic dysfunction might play a key role in the pathophysiology of restless legs syndrome (RLS), including the therapeutic effects of dopaminergic drugs and the results of several positron emission tomography and single photon emission computed tomography studies. However, RLS symptoms display a distinct circadian pattern, with an increase of both sensorial and motor symptoms in the evening and at night. Although the latter could also be caused by homeostatic mechanisms such as a linkage to the previous amount of wakefulness, several studies performed over the last few years under semiconstant, routine conditions have suggested the existence of a 'true' circadian mechanism modulating the severity of RLS symptoms across the day-night cycle. Thus, both periodic leg movements of sleep and restlessness show a maximal severity in timely coincidence with the falling phase of the core temperature circadian cycle. The present article reviews the evidence showing circadian oscillation of dopaminergic function and postulates that the amplitude of circadian rhythm of dopaminergic function is increased in RLS, with a hypofunction at night.