Understanding restless legs syndrome


The symptoms of restless legs syndrome sound so bizarre — creepy-crawly feelings and an uncontrollable urge to move the legs, especially at bedtime — that, until recently, many sufferers have simply not been believed.

Ron Blum, 38, a Boston e-mail marketer who got RLS as a 7-year-old, recalls that the minute he lay down and tried to sleep, “my left leg felt like it had to go for a walk.” Though he never told his parents, he’d get up and walk for hours in circles. It wasn’t until years later that a friend heard about RLS. “He called me up and said, ‘Ron, I know what you have. It has a name.’”

Today, RLS has not just a name but also a growing rap sheet.

In recent years, the neurological condition has been linked to increased hypertension, stroke, erectile dysfunction, higher death rates from kidney disease, possibly Parkinson’s disease and fibromyalgia, and perhaps other problems as well. RLS affects 12 million Americans, according to a National Institutes of Health website, though some researchers think the prevalence is higher and some, lower.

“You can think of RLS today as where sleep apnea was 10 to 15 years ago,” says Dr. John Winkelman, a psychiatrist, RLS expert and medical director of the Sleep Health Centers, which is affiliated with Brigham and Women’s Hospital. It’s even been dubbed “the most common disorder you’ve never heard of.”

“We used to think of sleep apnea as a bunch of fat guys snoring,” says Winkelman, who consults for drug companies that make RLS medications. “Now we know it’s a risk factor for heart disease, stroke, motor vehicle accidents. We are also just beginning to recognize the potential negative medical consequences of RLS.”

Not to mention the toll RLS takes on quality of life.

“There were many, many nights when I would sleep for only 21/2 or three hours,” recalls Roberta Kittredge, a 65-year-old retired teacher in Hampton, N.H., who, like many women, first got RLS when she was pregnant. (Studies suggest a link between RLS and high estrogen levels.) “Every night I went to bed positive I would sleep, and two or three minutes later, I was out of bed and walking the floor for hours and hours.”

Iron and dopamine

There is still no objective test for restless legs syndrome, but at long last, “we know what’s wrong. The neurobiology of RLS is definitely clear,” says Richard Allen, an associate professor of neurology at Johns Hopkins University.

In parts of the brain, levels of iron fall too low, which results in reduced availability of dopamine, a neurotransmitter that is also deficient in Parkinson’s disease.

If a person is prone to RLS — it often runs in families, and so far four genes have been linked to RLS or a related condition — and is also low on iron, there’s a good chance he or she will develop RLS. A study published in the May issue of Archives of Neurology showed that siblings of a person with RLS have a 3.6 times greater chance than normal of developing the condition. Replacing iron through supplements sometimes makes RLS go away.

The dopamine connection also helps explain why the condition has such a distinct circadian rhythm, says Allen, who consults for companies that make RLS drugs. Dopamine levels follow a clear 24-hour pattern, with levels lowest in the evening.

Moreover, presumably because both RLS and Parkinson’s involve low dopamine, some of the dopamine-enhancing drugs used to treat Parkinson’s, such as Mirapex and Requip, also help RLS patients.

Epidemiologist Xiang Gao of the Harvard School of Public Health, who has no ties to RLS drug companies, has shown that men with relatively severe RLS have nearly double the normal risk of erectile dysfunction. Dopamine plays an important role in erectile function.

Syndrome most severe at night

Restless legs syndrome, which can be triggered whenever a person has to sit or lie still, as on long plane trips or at concerts, is most severe at night, which is why it often affects sleep. And, once asleep, 80% of people with RLS also exhibit another condition, periodic limb movement during sleep (PLMS), in which the legs jerk as often as every 20 or 30 seconds. (PLMS can be measured objectively.)

Researchers from the University of Montreal and elsewhere have shown that each of these leg movements is associated with a dramatic increase in blood pressure, which may help explain the increased risk of hypertension and cardiovascular disease in RLS.

If this link is confirmed, the effect will be dramatic because “hypertension is a powerful predictor of premature death,” says Dr. David Rye, a neurologist at Emory University, who studies the genetics of RLS and PLMS and has the conditions himself. Rye, who consults for companies that make RLS drugs, and his team have a research paper on the links to hypertension in the works.

Curiously, receptors other than dopamine also play into RLS. Histamine, a neurotransmitter, is a powerful brain stimulant; drugs that block histamine — antihistamines such as Benadryl that induce drowsiness — can significantly exacerbate RLS symptoms.

It’s a complicated and still-emerging picture, and many people with the condition suffer in silence and shame. But patients like Kittredge can offer some hard-won advice: “Find an educated doctor … who understands RLS. There is hope out there. I am living proof.”

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