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Restless Legs Syndrome: Diagnosis, Treatment and Research


The symptoms of restless legs syndrome (RLS) often strike at night. Just when you sit down to watch television, put your feet up to read a book, or lay down to sleep, an unpleasant, irritating and sometimes overwhelming sensation in your legs won’t let you rest. You feel an increasing urge to move your legs that will not stop until you do. “Some people with RLS walk for hours at night before they can finally fall asleep,” says Johns Hopkins sleep expert Christopher J. Earley, M.B.B.Ch., Ph.D. “Or sensations in their legs wake them up over and over again.”

What’s going on? “RLS is a metabolic brain disease, most likely caused by an iron deficiency in the brain tissue,” explains Johns Hopkins sleep expert Richard P. Allen, Ph.D. “Genetics also plays a role. So does the brain’s ability to respond to the neurotransmitter dopamine.”

An estimated one in 10 Americans have RLS. For many, symptoms are mild or intermittent. But for the estimated 40 percent with moderate to severe RLS, the discomfort and lost sleep make daytime activities—working, going to school, keeping house and maintaining relationships—difficult.

Risk Factors

Knowing the risk factors can help you recognize restless legs syndrome and get treatment.

Family history. While no single gene seems to cause RLS, risk can be inherited. In one Johns Hopkins study, 19.9 percent of people with RLS had a parent, brother or sister with the condition. Having a second-degree relative with RLS—such as a grandparent, aunt or uncle—increased the odds somewhat.

Gender. Overall, women are twice as likely as men to experience mild to severe RLS symptoms. However, women who have not been pregnant have the same risk of RLS as men.

Low iron levels. About 15 percent of people with RLS have low scores on blood tests of the iron stores in their body—defined as a serum ferritin level below 50 mc/gl. (However, far more may have low brain-iron stores—see “Diagnosis and Treatment” for more information.)

Pregnancy. Up to one in five women develop RLS while pregnant, most often during the third trimester. It usually resolves within a few weeks or months of birth. However, having RLS during pregnancy triples your risk of developing chronic RLS later in life.

Medications. Many antidepressants and medications that block the neurotransmitter dopamine, can also trigger or aggravate RLS symptom. Anti-histamines that are centrally active commonly exacerbate RLS.

Diabetes and peripheral neuropathy. People with high blood sugar as well as nerve damage caused by diabetes may have a higher risk of RLS. Peripheral neuropathy can also make the symptoms more intense.

End-stage renal disease. Severe kidney disease that requires dialysis is associated with higher odds of RLS. Experts are still looking into the cause of this connection, but iron status appears to be a primary factor.

Diagnosis & Treatment


“There is no medical test for restless legs syndrome. Your doctor will use your answers to a set of key questions to determine whether you have the condition, as well as its severity,” Allen says.

It is likely you have RLS if you have all of these:

  • An urge to move your legs, usually accompanied by uncomfortable and unpleasant sensations in your legs.
  • The urge to move your legs and the unpleasant sensations begin when you’re resting or inactive—such as when you’re sitting down to watch TV or lying in bed.
  • The urge to move your legs and the uncomfortable sensations are relieved, at least partially, by activities like walking or stretching.
  • The urge to move your legs and the unpleasant sensations are at their worst in the evening or at night.
  • These symptoms are not caused by other health conditions such as muscle cramps, arthritis or reduced blood flow in the legs.


“Doctor-supervised iron supplementation, medications to relieve symptoms, and home strategies can all ease the symptoms of restless legs syndrome,” Earley says. Treatment options include:

Iron supplementation: Iron replacement therapy is emerging as an important RLS treatment. “We have found that iron therapy is an important but often overlooked treatment forRLS, but you should never start iron supplements on your own,” Allen says. “For some people, it can lead to a dangerous iron buildup in the body, if they have a condition called hemochromatosis.”

Your doctor may try oral iron supplements first while carefully monitoring your iron levels and symptoms. If RLS does not improve, iron infusions may help. For some people, symptoms clear up after one or two infusions, while others find they have to return for additional infusions. Who may benefit? Hopkins researchers have found that body stores of iron (measured with a serum ferritin test) are low in one in seven people with RLS, but iron stores in specific brain regions may be low in many more. Iron replacement may be recommended if your serum ferritin level is lower than 100 mcg/L.

“Iron replacement is effective and safe under a doctor’s care, but you may have to go to a medical center that the Restless Legs Syndrome Foundation has designated as a certified Quality Care Center for this treatment,” Earley says. (Find one at

Alpha-2-delta drugs: These medications help normalize electrical activity in nerve cells. Johns Hopkins experts recommend these as the first medication choice for most people with RLS. “These drugs take longer at first to bring relief than dopamine agonists but will not trigger worsening RLS symptoms over time—called augmentation—the way dopamine-boosting medications often do,” Earley says.

Dopamine agonists: Dopamine-related medications increase dopamine levels or dopamine signals in brain cells. Long considered the first-line treatment for RLS, Johns Hopkins experts now recommend using them only if alpha-2 drugs aren’t effective. “Dopamine-based drugs work quickly but have risks,” Earley says. About one-third of people who take them for two years develop worsening RLS symptoms, called augmentation. “The symptoms improve when the medication is stopped and other drugs can control them,” he says. “Using the lowest possible dose and taking these medications only in the evening, to control nighttime symptoms, can delay augmentation.”

Benzodiazepine receptor agonists: Antianxiety drugs and some new sleep aids are most helpful for people with mild symptoms. They may also help if you only experience sleep problems due to RLS once in a while.

Opioid pain relievers: These medications can ease symptoms in severe RLS that isn’t helped by other treatments. But side effects include nausea, constipation and a risk of dependence.

Living With …

At-home strategies may help ease the leg discomfort of mild to moderate restless legs syndrome. In addition, making healthy food choices could help maintain your iron stores.

Engage in moderate-intensity exercise. Regular physical activity may help reduce the severity of RLS by as much as 40 percent. “Avoid vigorous or extreme exercise. It can make symptoms worse,” Allen says. Aim for 30 minutes a day of an activity you enjoy, such as walking. To fit activity into busy days, take the stairs instead of the elevator, or park farther from the door at work or the supermarket.

Cut back on caffeine and alcohol. Some people experience milder symptoms when they reduce or eliminate alcoholic beverages and sources of caffeine (coffee, tea, cola soft drinks and chocolate) from their diet.

Use heat and cold. A hot bath, or applying hot and cold packs to your legs, may bring relief.

Massage your legs. Kneading and rubbing your leg muscles in the evening could help too. In one study of home care for RLS, participants said they got the most relief with this strategy.

Time your activities around symptoms. RLS usually follows a daily pattern, with more discomfort in the evening and overnight. If you can, plan travel and activities where you must remain in your seat (such as going to a concert or movies) for times of day when your RLS is less active. “Some people go to bed later at night and sleep later during the day too,” Allen says.

Distract yourself. Keeping your mind off the feelings in your legs—by reading, listening to a recorded book or music, playing cards or working on your computer—could help you cope better with mild symptoms.

Do your best to get enough sleep. Skimping on slumber could make symptoms worse.

Follow a healthy diet. Low iron stores are associated with more severe symptoms. A healthy, varied diet that includes foods rich in iron such as fortified breakfast cereals, legumes (such as white beans and kidney beans), green vegetables such as spinach, and lean red meats can help you maintain a healthier iron status. That’s especially important if you’re a woman in her reproductive years (menstruation can reduce iron stores) or are pregnant. However, diet alone is likely not enough to replenish the low iron that triggers RLS symptoms.

Related Conditions

Several health conditions are linked to restless legs syndrome. Among them:

Iron deficiency anemia: In one recent Johns Hopkins study, people with iron deficiency anemia were six times more likely to have RLS than people without low iron stores. They were also nine times more likely to have moderate to severe RLS symptoms that prevented them from getting a full night of restful sleep.

Periodic limb movement in sleep (PLMS): Up to 90 percent of people with RLS also have PLMS—rhythmic or semi-rhythmic movements of the foot, lower leg or whole leg while asleep. This can disrupt slumber, leading to daytime drowsiness.


Recent research by Johns Hopkins scientists is changing the way restless legs syndrome is treated. Two examples:

Iron replacements may put RLS symptoms in remission. In a study of people with RLS, 29 percent of those who received intravenous infusions of ferric carboxymaltose (FCM) saw symptoms go into remission. Six months later, 25 percent of those who had iron transfusions still did not need medication for RLS. “Iron replacement is not right for everyone, but it can markedly improve and even eliminate RLS symptoms,” Earley says.

Alpha-2 delta medications have advantages. In another study of people with RLS, Johns Hopkins researchers found that the drug pregabalin relieved symptoms in 71 percent of patients. But long-term use did not worsen RLS symptoms (a phenomenon called augmentation) the way the widely prescribed, dopamine-based medication pramipexole did. “We now recommend alpha-2 delta medications like pregabalin, gabapentin or gabapentin enacarbil first, to lower the risk of augmentation,” Allen says.


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