Conditions associated with reduced body iron content such as late stage pregnancy, advanced renal failure, and blood loss from frequent blood donations appear to precipitate RLS [36,37]. However, only 20-25% of patients with iron deficiency exhibit symptoms of RLS. Studies of cerebrospinal fluid, magnetic resonance imaging of the brain, and post-mortem tissue all demonstrate CNS iron deficiency in RLS. Recent therapeutic trials of oral and intravenously administered iron [38,39] have shown positive effects on the course of RLS in patients with iron deficiency or serum ferritin levels <45 mg/L. Contrasting findings were reported by Earley and coworkers [40] in a placebo-controlled study of high-dose intravenous iron sucrose in idiopathic RLS and normal iron status (serum ferritin >45 mg/L). Explanations for the discrepant results may include the type of iron formulation used, the dosing regimen, patient characteristics, or, importantly, the peripheral iron status with or without significant iron store depletion.

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