Restless legs syndrome and periodic leg movements in sleep

Restless legs syndrome (RLS) is a sensorimotor disorder that appears to affect at least 5% of the population. Women appear to be affected twice as commonly as men. The prevalence increases with age, as does disease severity. For many individuals with RLS there is significant sleep disruption and a general decrease in quality of life. RLS appears to be increased in subjects with iron deficiency, during pregnancy, and among those on hemodialysis. Cerebrospinal fluid, magnetic resonance imaging, and autopsy studies support the concept that RLS is associated with low brain iron levels, even in those who have no clear peripheral iron storage problems. Treatment studies, on the other hand, support a role for the dopaminergic system, as levodopa and dopamine agonists are considered the most effective agents for relieving RLS symptoms. Other treatments of value in RLS include opiates, benzodiazepine receptor agonists, and some anticonvulsants such as gabapentin. Because low brain iron appears to be a causal factor in RLS, treatment studies with oral or intravenous iron have been tried, with varying success. Finally, recent family studies and gene-wide association studies have identified several candidate genes; this may help to focus future research endeavors into the pathophysiology of RLS.