Probing Question: What is Restless Leg Syndrome, and how can it be cured?

Photo by James Collins

By Sarah Etter
Research/Penn State

At the end of a long day, most people look forward to a good night's sleep. But for the 10 percent of Americans who suffer from Restless Leg Syndrome (RLS), that sleep may be painfully elusive. RLS is a neurological disorder, often inherited, that causes unpleasant feelings or sensations in the legs. These sensations usually strike late in the evening, and symptoms tend to worsen the longer a person is at rest.

Doctors have described the symptoms of the disorder for centuries. In 1672, Sir Thomas Willis, an English physician wrote of "leapings and contractions" so intense that sufferers "are not more able to sleep than if they were in a place of the greatest torture."

Until now, however, no one could point to the source. Although many researchers had considered RLS a psychiatric condition, recent studies by neurologist James R. Connor at Penn State College of Medicine suggest that RLS actually may be caused by a deficiency of iron in the brain.

"Restless Leg Syndrome was not established as a true biological disorder before this research," said Connor. "Discovering the relationship between RLS and iron deficiency really shows that this condition is not psychiatric; in fact, it's quite the opposite."

After conducting studies on iron-deficient rats and sliced samples of human brain tissue, Connor's team found that people who suffer from RLS have unusually high levels of the enzyme tyrosine hydrocylase (TH) in the midbrain region known as the substantia nigra. TH regulates production of the neurotransmitter dopamine, which we associate with the sensations of pleasure, but which is also important for motor control.

Despite the excess TH, Connor found, sufferers lacked sufficient dopamine. The result, he posits, is a "misfire" in the neural signals from the brain to the legs, creating the "creepy-crawly" sensations characteristic of RLS. Since TH requires iron to produce dopamine, excess amounts of TH without sufficient amounts of iron result in an irregular distribution of dopamine throughout the brain. "If iron was present in sufficient amounts, the feedback process would signal cells to stop or slow TH production."

Does boosting a person's iron intake solve the problem? Not necessarily, Connor said. In some cases, RLS may be an inherited condition requiring different treatment. Currently, researchers are attempting to illuminate the relationship between genetics and iron deficiency, and the effectiveness of supplements administered both orally and intravenously.

For now, however, the Restless Leg Syndrome Foundation (RLSF) suggests taking hot or cold evening baths, exercising before bed and avoiding caffeine as much as possible. Stretching and practicing meditation or yoga also may help, as may maintaining a cool, clean sleeping area.

"Our next steps are to continue investigations of treatment strategies involving iron supplementation and dopamine agents to attempt to reach the normal balance between iron and dopamine in the brain," Connor said. "We hope these discoveries lead to a test that could diagnose this syndrome, and a potential for therapy to bring long-term relief to those who suffer with it."

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James R. Connor, professor and vice chair in the Department of Neural and Behavioral Sciences in the Penn State College of Medicine, can be reached at jrc3@psu.edu. For more Probing Questions, and other features about research at Penn State, visit Research/Penn State at http://www.rps.psu.edu/ online.