THE MYSTERY. Some people’s legs seem to have a mind of their own; they kick and thrash about in bed, keeping their owners (and anyone else in the bed) from sleeping. Yet this common—and often easily treatable—problem is rarely recognized in the medical profession, even among doctors whose family members suffer from it.
At lunch in the hospital cafeteria one of my colleagues asked me whether it would be worth his wife’s while to get evaluated for a sleep disorder. He was skeptical because she had not had a good night’s sleep for close to thirty years. But after he described the problem, I thought that it was worth looking into.
When I saw the doctor’s wife in the sleep clinic, she told a familiar tale. During her third and last pregnancy, thirty years earlier, she had developed an irresistible urge to move her legs when she tried to go to sleep. She couldn’t stop moving. She would toss and turn, but the only way she could find even temporary relief for her discomfort was by getting up and walking around. Because of this it was almost impossible for her to fall or stay asleep. She and her husband no longer shared a bed because the tossing and turning and recurrent awakenings disrupted his sleep as well. Her own interrupted sleep had created the usual daytime problems: lack of energy and a tendency to fall asleep at inconvenient times. She did not want to start on sleeping pills, and no one had been able to suggest another solution. After interviewing and examining her, I ordered some simple blood tests, which gave me the answer to her problem.
During pregnancy, many women suffer from a sleep disorder known as restless legs syndrome (RLS), abnormal and excessive movements of the legs while sleeping or trying to sleep. The second most common sleep disorder (after sleep apnea), it affects 15 percent of the general adult population of North America and 10 percent of the female population, yet general practitioners hardly ever diagnose it. It is much more common among older people, affecting 30 to 40 percent of people as they age; it also seems to run in families. It is likely that you or someone you know has this syndrome or will get it. Restless legs syndrome may be caused by various medical conditions, including iron deficiency, but it has other causes as well, and in many cases the cause is never found.
Most people with RLS complain of insomnia or restlessness at bedtime. Some will experience it in mild form, perhaps repetitive twitching during the night. Some patients say they have “crazy legs.” Some patients describe it as an irresistible urge to move their legs, some as a creepy-crawly sensation, either on the surface of the skin or, at times, below the skin. Often patients will say it feels as though insects are crawling under their skin. Others describe severe burning, itching, buzzing, or hot sensations in their feet or legs—when children complain of this sensation, it is often dismissed as “growing pains.” (Some RLS patients relate that when they were very young they were considered “squirmy” or restless children and were poor sleepers. The youngest child that I have seen with proven RLS was eight years old.) Most patients find some relief of these symptoms by moving around or walking. For many, the urge to move their feet or to walk around is irresistible. Some people fan their feet at night or apply cold wet towels to their legs. Some patients awaken with painful leg cramps, often in their calves.
Almost all RLS sufferers have trouble falling asleep, and more than three-quarters of them have trouble staying asleep, for even when they are asleep, the twitching does not stop. In roughly 80 percent of people with restless legs syndrome, twitches in their legs (and, less often, in their arms or other parts of their body) occur about every twenty to forty seconds. These twitches can easily be detected in a sleep laboratory. When more than five twitches per hour are present, the patient is diagnosed with periodic limb movement disorder (PLMD). A wide range of movements can occur in patients; some people look as if they are riding a bicycle in their sleep, whereas in other cases only the big toe moves. Sometimes the twitches are so subtle that although the monitors record their electrical activity, observers cannot see any movement. Patients with this milder form are less likely to be diagnosed because the twitching goes unnoticed. These patients need to have an overnight sleep study done.
Bed partners, who often suffer from secondhand sleep disruption, can help identify the patient’s RLS, especially if the patient has a movement or a twitch every twenty to forty seconds. Some sleepers with RLS might kick or hit their bed partner. The bed partners of RLS sufferers have told me that sometimes it feels like sleeping beside a wriggling fish, and bed partners might also develop insomnia because of the RLS sufferer’s excessive movements. Thus, most RLS patients have two problems: the unpleasant sensations that keep them from falling asleep, and the movements that awaken them or their bed partner. Frequently, couples start to sleep in separate beds and even in separate rooms.
As one woman, who went undiagnosed for forty years, described her experience, “I discovered I couldn’t sit still in movies or church and I was walking until three and four in the morning until exhaustion finally let me sleep. I was unable to describe what was happening in my legs. I try to describe the sensation as crawly things under your skin from the knee down, usually starting with a tingly feeling around the knee and then periodic jerks that caused the legs to jump. I have a very loving and sympathetic husband, but eventually we ended up in twin beds. Over the years it gradually got worse, especially with the start of menopause. I feared for what I might do, I got so exhausted and frustrated. I wondered how I could function with so little sleep. I began to panic. My thought at one time was: ‘Thank God I don’t live in a high-rise—anything to end this.’”
Although people complain that their symptoms are the most severe at bedtime, some patients develop an irresistible urge to move their legs or walk around when they are sedentary or in situations that require them to sit still. People with RLS might find it extremely difficult to sit in a car for a long trip; they might need the driver to stop the car frequently so they can get out and walk around. Or they might find it difficult to sit still in a movie theater, irritating the people around them by their constant fidgeting. Even when they are simply sitting in a chair, they might continuously move their legs or tap a heel. As one sufferer described it, “I had to stay still for a bone scan. It was forty-five minutes of sheer torture. Finally they tied my legs down with elastic bands and then had to hold them in place because the spasms were so strong.”
Some people with RLS fall asleep at the wrong time or in the wrong place during the day and this is the reason they seek medical help. Their main complaint is not the movements but their severe daytime sleepiness, which can drastically affect their personal and professional life. Even when they fall asleep, the continuous disruptions and movements result in poor sleep quality and sleepiness the next day. Some people find themselves overwhelmingly sleepy and yet unable to sleep. One person who sought help when he was thirty explained that he couldn’t sit still in the evening because his right leg would either jerk or get a bone-tickling feeling that forced him to move it. He rarely felt energetic when he got up in the morning no matter how much sleep he had had. For at least twelve years he would fall asleep as soon as he became inactive, no matter where he was; in college he would fall asleep in class and frequently go to the library for the sole purpose of sleeping between classes.
Often family members can help with a diagnosis of RLS. Bed partners, in particular, are likely to notice movement disorders in their partner. Someone with RLS will sleep fitfully and may get out of bed and return several times a night. He or she might change positions frequently even while sleeping or have repetitive twitches or movements of the legs or, sometimes, the arms. Sometimes they will even kick or hit out. Some RLS patients sweat profusely. If a bed partner shows these symptoms, he or she may have RLS and should bring this to the attention of the family doctor.
We have little data on how common RLS is in young children. A 2015 study found that it is present in probably 2–3 percent of North American children. I have seen it in children as young as eight. One way a parent might recognize a movement disorder in a child is if the child is a very restless sleeper. If he or she tosses, turns, and changes positions constantly, or if the bedclothes are in a tangle in the morning, it might indicate that a movement disorder is present. (It could also indicate that the child has a sleep-breathing disorder, which is discussed in Chapter 12.) If the child also falls asleep in class, it could be another indication that he or she has a movement disorder.
A great deal of research has recently been done on the relationship between attention deficit hyperactivity disorder (ADHD) and restless legs syndrome. For example, one study reported that children who were performing very poorly at school had severe insomnia caused by restless legs syndrome and low iron levels. When the iron levels were corrected, the symptoms vanished and the children’s grades improved in school. Parents whose children have been diagnosed with ADHD or ADD (attention deficit disorder) should look into the possibility that the problem might in fact be RLS before putting the child on unnecessary medications.
Restless legs syndrome and periodic limb movements in sleep are extremely common among the older population. The reasons for this are not entirely clear but may in part relate to the fact that many older persons have medical conditions that predispose them to the conditions. Movements may be more common in those with Parkinson’s disease, arthritis, anemia, diabetes, and heart disease. As in younger people, difficulty falling asleep and staying asleep may be a clue to a movement disorder.
Restless legs syndrome can be caused by a number of factors, which is another reason for getting an evaluation at a sleep clinic. What causes these excessive movements is just beginning to be understood by the sleep medicine community. The impulses that cause the increased movements appear to arise in the central nervous system. And the regularity of the twitches suggests that a pacemaker of some kind within the brain is triggering the movement. Recent research suggests that reduced levels of iron in the brain might play an important role in RLS.
Certain kinds of medication suppress the movements, and this, too, can give doctors an indication of what is causing a patient’s RLS. Drugs like ropinirole (Requip) and pramipexole (Mirapex), which increase the amount of dopamine or attach themselves to dopamine receptors in the nervous system, have been successful at treating RLS and suppressing the twitches. Dopamine is one of many chemicals the nervous system uses to send messages between cells. A person with reduced dopamine levels might therefore be more likely to develop RLS, and doctors should look for factors that might reduce dopamine in the central nervous system. For example, iron is involved in the production of dopamine. Reduced iron levels in the body, quite common in women, may be associated with RLS.
For many patients, RLS does not seem to be associated with another medical condition but is rather genetic. (It is quite common among people of French-Canadian descent, for example.) At least six different abnormalities in genes have been linked to RLS, and scientists have shown that RLS (especially if it starts early in life) is an autosomal dominant trait; a person must have one of two abnormal chromosomes to have the trait. Each child receives half of each parent’s chromosomes and thus has a 50 percent chance of inheriting this trait from a parent with RLS. The trait has variable penetrance; this means that even if a person carries the gene the symptoms can range from absent or mild to severe. Thus RLS can appear to skip generations. Sometimes families with RLS are found to have low vitamin B12 levels, which could indicate inefficient absorption of B vitamins.
Some medical conditions also lead to RLS, including iron deficiency, anemia, folic acid deficiency, vitamin B12 deficiency, osteoarthritis and rheumatoid arthritis, diabetes, kidney problems, and depression. People with one or more of these medical conditions are at increased risk for RLS and should consult their doctor.
Restless legs syndrome may occur in people with anemia (a reduced level of red blood cells), especially if it is caused by an iron or vitamin B12 deficiency. In fact, recent research has shown that iron deficiency, even when there is no anemia, might still cause RLS. People who donate blood frequently might be at greater risk of developing anemia and restless legs syndrome because when they donate blood they lose iron that might not be replenished by their diet.
Women are at a higher risk than men of developing anemia and iron deficiency because of the repeated loss of blood during the menstrual cycle. This can result in iron deficiency if they do not replace the lost iron in their diet.
Many women first notice restless legs syndrome during pregnancy. About a quarter of pregnant women have RLS by the third trimester. (If RLS is present before pregnancy the symptoms will worsen but may vanish after the birth of the baby.) The fetus is taking iron from the mother, so if her dietary intake of iron does not keep up with what the fetus is taking, she will develop iron deficiency. RLS can also be caused by a deficiency in folic acid, one of the B vitamins, which plays a role in the production of red blood cells. Folic acid deficiency has become less common in North America because of fortification of grains but still occurs. Having adequate folic acid levels during early pregnancy has been linked to a reduced risk of birth defects such as spina bifida.
Because of the importance of B vitamins to red blood cell production, RLS may be more common among people with low levels of vitamin B12. In particular, it might be found among patients (usually older people with pernicious anemia) who do not absorb adequate amounts of B12 from the gastrointestinal tract. Other gastrointestinal disorders such as ulcerative colitis and Crohn’s disease might also block the absorption of vitamins or iron and lead to RLS.
Millions of North Americans diet to become or stay thin, and this may result in their not getting enough nutrients from food. A diet deficient in certain nutrients such as iron and vitamin B12 can cause RLS or worsen an already existing case. At the sleep clinic, we have seen RLS caused by low levels of iron in people who avoid red meat or are strict vegetarians.
RLS is also more common in diabetics. This is because of the effect diabetes has on the nervous system. When diabetes has been present for many years, it can damage nerves, resulting in neuropathy, which is believed to be a cause of RLS. About half of all patients with kidney failure who are treated with dialysis have RLS.
At the sleep clinic, we have also found that RLS is more common in people with diseases such as osteoarthritis or rheumatoid arthritis. This disorder has frequently appeared in people waiting for implantation of artificial joints. We do not yet know the reason these diseases are linked to RLS. The RLS might represent a reaction to the pain caused by these conditions.
The right treatment for RLS can be prescribed only when the syndrome has been correctly diagnosed. Many doctors do not ask patients about the quality or quantity of their sleep or whether they have symptoms of RLS. People with RLS are too frequently diagnosed with depression and treated with antidepressants. In some cases they might actually be clinically depressed, but often the patients have not been asked about the symptoms of RLS before they are treated for depression. People with severe restless legs syndrome are often very sleepy during the day, and this desire to sleep all the time, along with disturbed sleep at night, can be misinterpreted as a symptom of depression. Compounding the problem, some of the drugs used to treat depression, such as antidepressants, can make RLS worse. At the sleep clinic we have also seen many patients who had been diagnosed as having chronic fatigue syndrome or fibromyalgia who actually had RLS. RLS is perhaps the most common medical condition that doctors fail to diagnose. Patients who suspect they have a movement disorder or are being treated for depression need to talk to their doctor about the possibility that they have RLS and be sure to describe all their symptoms carefully.
When we get a patient at the sleep clinic whom we think might have RLS, we follow a standard sequence to make our diagnosis. First we take a medical history of the patient. This is followed by a complete clinical interview and often a variety of tests.
We expect to find the following symptoms:
Less commonly, other muscles (arms or back) may be affected.
If we believe that the patient might have RLS, we order blood tests to see whether anemia is present. Red blood cells contain a pigment called hemoglobin that carries oxygen. When the number of red blood cells or the amount of hemoglobin is too low, anemia is present. Three factors—iron, vitamin B12, and folic acid—are involved in the production of red blood cells and are thus believed to play a role in causing RLS. Iron is found in the red cells and in the bone marrow where the red cells are produced. Iron is also carried by ferritin, the body’s major iron-storage protein. The most reliable way to detect iron deficiency, other than examining a bone marrow specimen, is to run a complete blood count and measure the ferritin level.
Even when the blood count is normal, however, the body’s iron stores might be reduced. The range of normal ferritin levels is wide, but within the normal range, the lower the ferritin level, the more likely it is that the person is iron deficient. The National Institutes of Health suggest that a ferritin value of less than 75 micrograms per liter in a person with RLS indicates that iron deficiency might be a causative factor. One problem with the ferritin level test is that the level might be elevated when the patient has certain acute or chronic illnesses or inflammatory diseases that mask an iron deficiency.
In some cases the patient might need an overnight sleep study. To monitor movements, activity of the anterior tibialis muscle (the muscle over the shins) is recorded. The sleep study could reveal that the patient takes a long time to fall asleep, tossing, turning, and trying to find a comfortable position.
Patients with RLS show an increase in activity of the anterior tibialis muscles while they are awake. After the patient falls asleep (which may take hours), we frequently detect the repetitive twitches in the muscles, occurring every twenty to forty seconds, symptoms of periodic limb movement disorder.
Although the diagnosis of PLMD is established when there are more than five repetitive twitches per hour of sleep, most patients have many times that number. RLS patients usually have between thirty and a hundred twitches per hour of sleep. When we observe the patients during the sleep test, we can usually see the repetitive movements. But even slight twitches can be detected because each time the patient twitches, his or her pulse (heart rate) increases.
Sometimes patients complain to their physicians about daytime sleepiness; they do not have prominent symptoms of insomnia or restlessness at bedtime but do have repetitive twitches during the night. A sleep clinic evaluation will establish that many of these twitches are linked to brief awakenings of the brain. These short awakenings not only change the brain waves, they also temporarily increase the heart rate. So the quality of sleep decreases, and this could cause sleepiness during the day. People experiencing extreme sleepiness should ask their doctor whether a sleep test is appropriate. The sleepiness could be caused by RLS, although it might also be the result of a coexisting problem such as sleep apnea (see Chapter 12) or narcolepsy (see Chapter 13).
Complete blood count to check for anemia
Studies (ferritin, serum iron, total iron-binding capacity) to check for reduced iron levels
Vitamin B12 level
Folic acid level
Sleep study
After RLS is diagnosed, a treatment can be prescribed. The type of treatment will depend on how severe the problem is and what the tests uncover. Sometimes no cause can be determined.
At the sleep lab we do not recommend that people treat themselves. Self-treatment without a correct diagnosis can be dangerous. For example, although iron deficiency might be the result of heavy periods or pregnancy, it could also be the result of a serious medical condition such as colon cancer or an inflammatory bowel disease. Taking large amounts of iron if you do not have a severe iron deficiency could lead to serious medical problems.
So if a patient is diagnosed as iron deficient, the cause of the iron deficiency then needs to be determined. If iron deficiency is the cause of RLS, the doctor should prescribe iron, usually in the form of tablets, to be taken for several months. Only about 1 percent of iron taken by mouth is absorbed, so it takes a long time to replenish iron stores in the body. Many preparations or multivitamins contain so little iron that they do not replenish the body’s iron stores. The doctor should recommend a preparation that contains the proper amount of absorbable iron. For people, particularly children, who have trouble taking iron tablets, fruit-flavored liquid iron preparations are available. People who become constipated from taking iron supplements could eat prunes; these contain iron and will also help with constipation. In rare cases, injections of iron can be used to treat iron deficiency. The good news is that when treated correctly, improvement can be dramatic. It has been my experience, however, that if the iron deficiency has been present for many years, the RLS might not resolve with iron replacement.
Some people with RLS have a vitamin B12 deficiency because they do not absorb B12 properly from the gastrointestinal tract. These people often require repeated B12 injections.
Women who are pregnant and have an iron or folic acid deficiency should speak to the doctor about proper supplementation. Since red meat is the major source of iron in the Western diet, vegetarians need to find other sources. In particular they need to ensure that they take in enough of the foods (for example, bran flakes, chickpeas, beans, and spinach) that contain significant amounts of iron. Vitamin B12 is found mainly in meat, eggs, and dairy products. Although some plant products contain vitamin B12, they are not as reliable sources of this important vitamin. Vegetarians should consider taking vitamin B12 supplements or eat fortified products to maintain a daily intake of 1.5 micrograms per day (or 2 micrograms during pregnancy).
If the RLS seems to be associated with a condition causing pain, such as arthritis, one management approach is to treat the patient’s underlying medical condition. The doctor might prescribe a medication such as a nonsteroidal anti-inflammatory like celecoxib (Celebrex) to treat the arthritis and/or the pain.
Many antidepressants cause RLS symptoms. If the RLS is clearly associated with the use of antidepressant medications, patients should discuss the issue with their doctor, who could suggest alternative treatments. Antidepressants are available that are not associated with restless legs.
Frequently doctors cannot determine an obvious cause of a patient’s RLS. In such cases, drugs to reduce movements could be prescribed as a treatment option. Three such drugs have been approved for use in the United States by the FDA. Two are medications that are often used to treat Parkinson’s disease and one is an anti-epilepsy medication.
Dopamine agonists. Drugs that increase dopamine levels or attach to dopamine receptors in the nervous system have been found to be an effective treatment for RLS. These are the same types of medications used for Parkinson’s patients, but at a smaller dosage. Parkinson’s disease is also a movement disorder in which dopamine levels are reduced in parts of the brain. The prescription pills pramipexole (Mirapex) and ropinirole (Requip) and the patch rotigotine (Neupro) have been approved for treatment, but patients should take care to follow their doctor’s recommendations on how to take them. These medications can have serious side effects, such as daytime sleepiness, worsening of symptoms as the drugs’ effect wears off, and, rarely, a tendency toward risk-taking behavior such as gambling.
Anti-epilepsy medications. Another approach, which has become a first-line treatment, is to use drugs that reduce the brain’s response to the excessive movements. These drugs permit the brain to ignore or suppress the movements. One drug that has been approved is gabapentin enacarbil (Horizant). Another anti-epilepsy drug that has been prescribed, especially if falling asleep is difficult, is clonazepam, which is in the class of benzodiazepines (see Chapter 20). Sometimes these medications might still be taking effect after the patient wakes up, resulting in a hangover. Those patients might find that taking the medication one or two hours before bedtime helps counter this side effect.
Devices. A device that applies vibrations to the legs (Relaxis) has been approved by the FDA to treat RLS.
For resistant cases. In the most severe cases, when other treatments have not proved effective, we might recommend low doses of codeine or another opiate medication at bedtime, a treatment that has been known to be effective for many years. These are narcotics and are generally classified as controlled substances. How these drugs work is not clear, but they have an effect of decreasing activity in some parts of the nervous system. For example, codeine can suppress the cough center. Patients should discuss this type of medication carefully with their doctor and review the possible side effects.
Other recommendations. Lifestyle modifications can also help decrease RLS. These might include decreasing caffeine and avoiding alcohol and nicotine. Moderate exercise might be helpful, as well as relaxation techniques, massage, and putting hot or cold compresses on the limbs. Some people find that cooling their legs or feet at night helps them; others find the opposite. RLS is truly a mystifying disorder.
The patient had restless legs syndrome, brought on by iron deficiency–related anemia. Her tests revealed a very low ferritin level, a low level of hemoglobin, and decreased red blood cells. We did not need to give her a sleep test because her clinical history was so typical of RLS. The treatment we prescribed was to take iron supplements. Three months later, to the astonishment of her husband, her RLS symptoms, which had been present for thirty years, were completely resolved and her sleep became normal.
Many doctors don’t know enough or don’t ask the right questions about women’s sleep disorders, even when the patient is a relative. Restless legs syndrome is a common disorder that causes insomnia. It is particularly problematic in women because it frequently comes on during pregnancy and can also be related to the blood loss of menstrual cycles, which lowers iron levels. It is also extremely common in elderly women. But most patients with RLS can be treated if they can get a correct diagnosis.