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).
Normal substantia nigra cells hold plenty of transferrin receptors - iron's gateways.
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.
