A clinical primer on restless legs syndrome: what we know, and what we don't know

Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a common sensorimotor disorder that may be idiopathic (primary) or secondary to a diverse group of conditions. The pathophysiology of primary RLS is only partly understood, but a strong association with brain iron deficiency possibly resulting in impaired dopaminergic function has been recognized. Genomic studies have established a genetic basis for primary RLS as well, and at least 42% of people with primary RLS possess a first-degree relative with the disorder. Secondary RLS is often associated with renal insufficiency, pregnancy, iron deficiency anemia, diabetic neuropathy, and Parkinson's disease. Approximately one-fourth of pregnant women experience RLS, with more intense symptoms experienced during the third trimester, and resolution of symptoms typically occurring within a few months after delivery, though RLS may resolve as early as 2 weeks after delivery. Restless legs syndrome is associated with increased prevalence of mood disturbances, sleep disturbances, and an impaired quality of life. The diagnosis of RLS involves 4 essential criteria related to a compelling urge to move the legs with an accompanying unpleasant sensation in the legs that is worse in the evening and at rest and improved by movement. Treatment of RLS incorporates both pharmacologic and nonpharmacologic approaches. Dopamine agonists are the mainstay of RLS treatment, but other therapies, including gabapentin, benzodiazepines, and low-potency opioids, are also commonly employed.