Restless Legs and Brain Iron Management
abstract & commentary
Source: Earley CJ, et al. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 2000;54:1698-1700.
Anxietas tibiarum (restless legs syndrome, rls), an ultimately irresistible compulsion to move the legs, usually benign but occasionally a harbinger of peripheral neuropathy, responds to several medications including L-dopa/carbidopa, dopamine agonists, clonazepam, and imipramine. Iron supplements, even in the absence of iron deficiency, have also long been known to be beneficial but for unknown reasons (Acta Med Scand 1953;145:453-457). Serum and cerebrospinal fluid (CSF) iron, ferritin (the primary iron storage protein in the brain), and transferrin (the primary iron transport protein in the brain) were assayed in 16 RLS patients (mean age, 64.2 years) and eight age-matched healthy controls (mean age, 61.2 years) to determine if brain iron concentrations were decreased in RLS.
CSF iron levels were not significantly different between the groups, serum iron was normal, and serum ferritin and transferrin levels were similar in both groups. However, CSF ferritin was lower (P = 0.0002), and CSF transferrin was higher (P = 0.018) in RLS compared to controls, supporting the hypothesis that brain iron concentrations are low in RLS, and explaining why iron supplementation helps alleviate its symptoms.
Commentary
Up to 10-15% of the population may suffer from RLS, 80% of whom also experience periodic leg movements of sleep (PLMS), the combination of which fragments sleep and results in impaired sleep onset and sleep maintenance, with consequent excessive daytime drowsiness (Sleep 1994;17:739-743; Mov Disord 1995;10:634-642; Mayo Clin Proc 1997;72:261-264). PLMS, however, although particularly common in the elderly, are not associated with RLS. Diagnosis is based on history, although sleep studies may help to identify PLMS. Differential diagnosis includes nocturnal leg cramps and neuroleptic-induced akathisia. If dopamine or dopamine agonists are ineffective, opioids (oxycodone, methadone) may be used alone or in combination with the above. And don’t forget the iron. —mr
Which of the following statements is true?
a. RLS is often associated with periodic leg movements of sleep.
b. RLS is a diagnosis made on history.
c. Differential diagnosis of RLS includes nocturnal leg cramps, peripheral neuropathy, and neuroleptic-induced akathisia.
d. If dopamine or dopamine agonists are ineffective, opioids (oxycodone, methadone) may be used alone or in combination with the above for RLS.
e. All the above
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