Why do restless legs occur at rest?—pathophysiology of neuronal structures in RLS. Neurophysiology of RLS (part 2)

Restless legs syndrome (RLS) is a heterogeneous disorder encompassing genetically caused types with early onset and acquired varieties occurring later in life. Genetic studies in the near future will most likely discover more than one causative gene. The acquired cases too have different etiologies ranging from idiopathic types to secondary forms with uremia, iron depletion, polyneuropathy and others. Here we aim to correlate typical RLS symptoms, such as the sensory symptoms at rest, the reduction of the complaint in response to movement or other physical stimuli, the dominant involvement of the legs, pain, circadian rhythm, and the responsiveness to dopaminergic drugs with neurophysiological features of the central nervous system. We outline the complexity of the neural structures involved and their connections. A diversity of hypothetical affections of different neuronal levels might lead to various combinations of RLS symptomatology. No single pathophysiological explanation has yet been developed that covers all clinical features.