Spring 2004 Volume 16, Number 3	Ironing Out RLS
	Recent studies by neurologist Christopher Earley, M.D., Ph.D., point to lowered stores of iron in key parts of the brain as a basis of restless legs syndrome (RLS).
Over the years, Earley had collected a mass of indirect evidence: Pregnant women who develop RLS's hallmarks-uncomfortable sensations in their legs and the overwhelming urge to move them-are iron-deficient. Lower blood serum levels of ferritin, a storage form of the mineral, mean more severe symptoms in patients. Patient MRIs reveal lowered brain iron in the substantia nigra, an area tied to initiating movement. But this year, his brain autopsy reports give direct results. Using the new technique of laser capture, which pulls specific cells for study out of tissues, his team measured iron directly in patients' neuromelanocytes, the key substantia nigra cells. No surprise: They were low in iron. And as important, the system that keeps iron levels on an even keel, the fine balance of proteins that oversee iron's movement into substantia nerve cells, looks out of whack. "You'd think that having low iron would heighten the body's ability to take it into cells-to maximize what exists," says Earley. "But that's not the case in the RLS patients." Their cells had fewer of the receptors that serve as gateways for transported iron. "The disorder appears to be an iron-regulation problem," he adds, "one that may have a genetic basis." Earley is readying microarray studies to see if iron-handling genes are abnormally switched on or off in RLS patients. "Many of our patients respond well to intravenous iron treatments," he says, "but this approach will help understand those who don't." For information, call 410-550-1044.