Clinical meaning
Restless leg syndrome (RLS, Willis-Ekbom disease) is a sensorimotor neurological disorder characterized by an irresistible urge to move the legs, usually accompanied by uncomfortable sensations (crawling, tingling, aching, pulling). Symptoms occur at rest, worsen in the evening/night, and are temporarily relieved by movement. The pathophysiology involves dopaminergic dysfunction in the basal ganglia (explaining response to dopamine agonists) and brain iron deficiency (iron is a cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis). Even with normal serum ferritin, CNS iron stores may be depleted. Secondary causes include iron deficiency (ferritin < 50 is significant in RLS), pregnancy (especially third trimester), chronic kidney disease/uremia, peripheral neuropathy, and medications that worsen RLS (antihistamines, antidopaminergic drugs like metoclopramide, SSRIs/SNRIs).
Exam relevance
Risk factors: - Iron deficiency (ferritin < 50 ng/mL — even without anemia) - Chronic kidney disease/ESRD (uremic RLS) - Pregnancy (especially third trimester) - Family history of RLS (autosomal dominant pattern in primary RLS) - Medications: antihistamines, dopamine blockers (metoclopramide), SSRIs/SNRIs, antipsychotics - Peripheral neuropathy - Female sex (slightly higher prevalence)