Restless legs syndrome: pathophysiology and the role of iron and folate

Restless Legs Syndrome (RLS) is a common movement disorder characterized by a circadian variation in symptoms involving an urge to move the limbs, usually the legs. Pregnant women, patients with end-stage renal disease or iron-deficiency anemia, and children with attention deficit hyperactivity disorder (AD/HD) have a significantly higher prevalence of RLS. The classic presentation includes the onset or worsening of symptoms when at rest and the circadian pattern of exacerbation of symptoms at night. These symptoms reflect a circadian fluctuation of dopamine in the substantia nigra. Patients with RLS have lower levels of dopamine in the substantia nigra and respond to iron administration. Iron, as a cofactor in dopamine production, plays a central role in the etiology of RLS. Folic acid administration has also been shown to alleviate the symptoms of RLS and may play a role in the treatment of primary (familial) RLS.