Leg Disorders (Restless Legs Syndrome and Nocturnal Leg Cramps)

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Leg Disorders (Restless Legs Syndrome
and Nocturnal Leg Cramps)

WHAT IS RESTLESS LEGS SYNDROME AND ITS SYMPTOMS?

Restless legs Syndrome (RLS) (also called Ekbom's syndrome) is a poorly understood disorder affecting up to 5% of the general population. Characteristics of RLS include the following:

RLS is sometimes described as a sense of unease and weariness in the lower leg that is relieved by movement. It is often accompanied by an inability to fall asleep.
Patients may describe the symptoms as "pulling, searing, drawing, or crawling" beneath the skin, usually in the calf area.
Itching and pain may be present.
About 80% of patients with RLS also experience periodic limb movement disorder, also called PLMD (formerly known as nocturnal myoclonus). In PLMD, the leg muscles involuntarily and repetitively contract and jerk every 20 to 40 seconds during sleep. The contractions occasionally arouse patients, but often they are unaware of the interruption. (It should be noted that PLMD is a specific disorder and only about 30% of people with it also have RLS.)
These sensations may also affect thighs, feet, and even arms. In fact, a small 2000 study suggested that nearly half of patients may experience RLS-type symptoms in the upper part of the body, specifically the arms.
At night the unpleasant sensations and the resulting uncontrollable urge to move the legs can often disturb sleep. Throughout the day the patient may feel compelled to move his or her legs in order to relieve the symptoms.

Symptoms typically occur at 30 to 60 second intervals when the legs are at rest (ie, sitting or lying). Symptoms of PLMD and RLS usually fall between 10:00 PM and 4:00 AM, being at their worst right after midnight. Symptoms are at their lowest level between 9:00 and 11:00 AM. Such periodic events indicate that these conditions may be influenced by circadian rhythm (the normal cycle of biologic activity over a 24-hour period).

Some experts now believe there are two forms of RLS, early- and late-onset, and that each has different characteristics:

One study reported that people with the onset of RLS in adolescence or earlier tend to have a family history of the disorder and to have RLS without accompanying pain.
Those with later onset tend not to have a family history of RLS and may have a higher rate of pain in the lower extremities.

HEALTHY SLEEP

Circadian Rhythm

In sleep studies, subjects spend about one-third of their time asleep, suggesting that most people need about eight hours of sleep each day. Individual adults differ in the amount of sleep they need to feel well rested, however. (Infants may sleep as many as 16 hours a day.)

The daily cycle of life, which includes sleeping and waking, is called a circadian (meaning "about a day") rhythm, commonly referred to as the biologic clock. Hundreds of bodily functions follow biologic clocks, but sleeping and waking comprise the most prominent circadian rhythm. The sleeping and waking cycle is approximately 24 hours. (If confined to windowless apartments, with no clocks or other time cues, sleeping and waking as their bodies dictate, humans typically live on slightly longer than 24-hour cycles.) It usually takes the following daily patterns:

Humans are designed for daytime activity and nighttime rest.
Additionally, there is a natural peak in sleepiness at mid-day, the traditional siesta time.

In addition, daily rhythms intermesh with other factors that may interfere or change individual patterns:

The fraction-of-a-second-firing of nerve cells in the brain may be faster or slower in different individuals.
The monthly menstrual cycle in women can shift the pattern.
Light signals coming through the eyes reset the circadian cycles each day, so changes in season or various exposures to light and dark may unsettle the pattern. The importance of sunlight as a cue for circadian rhythms is dramatized by the problems experienced by people who are totally blind: they commonly suffer trouble sleeping and other rhythm disruptions.

The Response in the Brain to Light Signals

The response to light signals in the brain is an important key factor in sleep:

Light signals travel to a tiny cluster of nerves in the hypothalamus in the center of the brain, the body's master clock, which is called the supra chiasmatic nucleus or SCN.
This nerve cluster takes its name from its location, which is just above ( supra) the optic chiasm. The optic chiasm is a major junction for nerves transmitting information about light from the eyes.
The approach of dusk each day prompts the SCN to signal the nearby pineal gland (named so because it resembles a pine-cone) to produce the hormone melatonin.
Melatonin is thought to act as the body's time-setting hormone. The longer a person is in darkness the longer the duration of melatonin secretion. Secretion can be diminished by staying in bright light. Melatonin also appears to serve as a trigger for the need to sleep.

Sleep Cycles

Sleep consists of two distinct states that alternate in cycles and reflects differing levels of brain nerve cell activity. During a normal night's sleep, one progresses through these stages about five or six times:

Non-Rapid Eye Movement Sleep (NonREM). NonREM sleep is also termed quiet sleep. NonREM is further subdivided into three stages of progression:

Stage 1 (light sleep).
Stage 2 (so-called true sleep).
Stage 3 to 4 (deep "slow-wave" or delta sleep).

With each descending stage, awakening becomes more difficult. It is not known what governs NonREM sleep in the brain. A balance between certain hormones, particularly growth and stress hormones, may be important for deep sleep.

Rapid Eye-Movement Sleep (REM). REM sleep is termed active sleep and is believed by some experts to be regulated by the circadian clock in the hypothalamus. Most vivid dreams occur in REM sleep. REM-sleep brain activity is comparable to that in waking, but the muscles are virtually paralyzed, possibly preventing people from acting out their dreams. In fact, except for vital organs like lungs and heart, the only muscles not paralyzed during REM are the eye muscles. REM sleep may be critical for learning and for day-to-day mood regulation. When people are sleep-deprived, their brains must work harder than when they are well rested.

The REM/NREM Cycle. The cycle between quiet (NREM) and active (REM) sleep generally follows this pattern:

After about 90 minutes of NonREM sleep, eyes move rapidly behind closed lids, giving rise to REM sleep.
As sleep progresses the NonREM/REM cycle repeats.
With each cycle, NonREM sleep becomes progressively lighter, and REM sleep becomes progressively longer, lasting from a few minutes early in sleep to perhaps an hour at the end of the sleep episode.

WHAT CAUSES RESTLESS LEGS SYNDROME?

The primary cause of restless legs syndrome is not known. Researchers are investigating neurologic problems that may arise either in the spinal cord or the brain. Such problems most likely have a genetic basis in many cases.

Neurologic Abnormalities in the Spine

Some evidence suggests that restless legs syndrome may be due to nerve impairment in the spinal cord. Until recently, this was believed to be located in the lower back. A recent study reporting symptoms in the arms, however, suggests that nerve damage may occur in the upper spine.

Neurologic Abnormalities in the Brain

Other researchers believe that the neurologic abnormalities involved with RLS are more likely to originate in the brain and be due to imbalances in certain neurotransmitters (chemical messengers in the brain). A variety of studies support the hypothesis that an imbalance in the neurotransmitters dopamine and serotonin may play a part in RLS. Dopamine and serotonin unleash an array of nerve impulses that affect muscle movement. Genetic factors may be a factor in dopamine imbalance. A similar effect is seen in Parkinson's disease, and indeed, drugs that increase dopamine are used for both disorders [ see Medications for Restless Legs Syndrome below ].

Iron Insufficiency

Iron deficiency has been linked to RLS in some people and may affect dopamine receptors in the brain. In one 2001 study of 10 people, for example, magnetic resonance imaging (MRI) scans found iron insufficiency in parts of the brains of RLS patients. Other studies have also found an association and some suggest that RLS may occur in between 25% and 30% of people with iron deficiencies.

WHAT ARE THE RISK FACTORS FOR RESTLESS LEGS SYNDROME?

Leg restlessness at bedtime occurs in more than 15% of adults. It is more common in women than in men, and its prevalence increases with age. Up to half the people with RLS have a family history of the disorder. In about 40% of patients, RLS begins in adolescence.

Attention Deficit Hyperactivity Disorder (ADHD)

RLS and periodic limb movement disorder are thought by some experts to be strongly associated with attention-deficit hyperactivity disorder (ADHD) in some children. One study suggested that a quarter of children diagnosed with ADHD also has RLS or PLMD, and this may actually contribute to inattentiveness and hyperactivity. More research is needed to determine if RLS is a cause of some cases of ADHD or if it simply aggravates it. The disorders have much in common, including poor sleep habits, twitching, and the need to get up suddenly and walk about frequently.

Medical Conditions

People with the following medical conditions have a higher-than-average incidence of RLS. Some of these conditions may cause RLS and in some patients RLS and these medical conditions may have a common cause. Many people, however, have RLS without any of these problems:

Pregnancy. As many as 25% of pregnant women experience restless legs. In one 2001 study, RLS in this population was strongly associated with folate deficiencies (which in turn reduce iron levels).
Osteoarthritis. (About 72% of RLS patients have osteoarthritis.)
Varicose veins. (They occur in 14% of RLS sufferers.)
Diabetes.
Iron Deficiency Anemia.
Fibromyalgia.
Rheumatoid arthritis.
Kidney failure. (The risk is very high in people on dialysis.)
Emphysema.
Chronic alcoholism.
Many muscle and nerve disorders.
Hereditary ataxia, a group of genetic diseases that affect the central nervous system and are associated with many medical condition. Some experts believe that this may supply clues for the genetic cause of RLS.

Environmental and Dietary Factors

A number environmental and dietary factors can worsen or provoke RLS:

Smoking.
Alcohol abuse.
Caffeine.
Stress.
Fatigue.
Prolonged exposure to cold.
Iron or folic acid deficiencies.

Medications

Drugs that worsen or provoke the condition include:

Antidepressants.
Antipsychotic drugs.
Beta blockers.
Antihistamines.
Oral decongestants.
Diuretics.
Asthma drugs.

HOW SERIOUS IS RESTLESS LEGS SYNDROME?

Daytime Sleepiness and Its Consequences

Restless legs syndrome rarely results in any serious consequences. But in some cases, severe and persistent symptoms can cause considerable mental distress, chronic insomnia, and daytime sleepiness. [For more information see the Report #27, Insomnia.]

Sleep deprivation, and the daytime sleepiness that follows, is increasingly recognized as a cause of mood disruption and contributor to industrial errors and motor vehicle crashes. Insomnia costs the US approximately $13.9 billion each year in direct medical costs and unknown billions from decreased productivity and consequences of accidents.

Increased Risk for Accidents. As many as 200,000 automobile accidents in the US and 1,500 deaths from such accidents are caused by sleepiness. Studies continue to report that drowsy driving is as risky as drunk driving. The following are some examples:

Estimates on fatigue as a cause of automobile crashes range from 1% to 56%, depending on the study.
A large 1997 survey indicated that accidents involving motor vehicles or machine tools occurred twice as often in persons with moderate or severe daytime sleepiness, compared with those without daytime sleepiness.
In a major 1995 poll, 33% of those surveyed said they had fallen asleep while driving, and 10% of these people had had accidents because of this.
An Australian study reported that 17 hours of sleep deprivation cause impaired performance levels comparable to those found in people who have blood alcohol levels of 0.10%, a level that defines intoxication in many states.

Negative Effect on Thinking and Performance. Studies suggest that insomnia worsens many waking behaviors including the following:

Reduced concentration. Some experts report that deep sleep deprivation impairs the brain's ability to process information.
Impaired task performance . One study reported that missing only two to three hours of sleep every night for a week significantly impaired performance and mood. • Effect on learning. One study indicated that healthy sleep is important for learning certain perceptual skills related to visual patterns as well as repetitive skills, such as typing. Some studies reported no difference in test scores between people with temporary sleep loss and those with full sleep, although a Canadian study found that students who slept after cramming for an exam did better than those who stayed awake.

Effects on Emotions. One study reported that 20% of people with insomnia suffer from major depression. Although stress and depression are major causes of insomnia, insomnia may also increase the activity of the hormones and pathways in the brain that can produce these emotional problems. Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood.

Alcohol and Substance Abuse

Treatments for RLS. Medications used to treat RLS, such as the anti-anxiety agents (benzodiazepines) and opiates, can become habit forming and addictive.

Alcohol Abuse. A study found that people with insomnia were more likely to use alcohol for inducing sleep than people without insomnia. It should be noted, however, that a drink or two does no harm and may be helpful in people who are not at risk for alcoholism.

Psychiatric Effects

Some experts believe that many cases of RLS are due to underlying anxiety or depression. A 2001 study in Swedish working-aged women reported that women with RLS were more apt to be socially isolated, to have frequent daytime headaches, and to complain of problems at work due to sleepiness. The study suggests that emotional issues are more likely to be due to RLS than the other way around.

HOW IS RESTLESS LEGS SYNDROME DIAGNOSED?

Taking a Sleep History

A diagnosis of restless legs syndrome or nocturnal leg cramps often relies solely on the patient's description of symptoms. In general, the recommended approach is first to take a sleep and personal history. The physician may begin an interview that may include the following questions:

How would the sleep problem be described?
How long has the sleep problem been experienced?
How long does it take to fall asleep?
How many times a week does it occur?
How restful is sleep?
What are the leg problems like (cramps, twitching, crawling feelings)?
What is the sleep environment like? Noisy? Not dark enough?
What medications are being taken (including the use of self-medications for insomnia, such as herbs, alcohol, and over-the-counter or prescription drugs)?
Is the patient taking or withdrawing from stimulants, such as coffee or tobacco?
How much alcohol is consumed per day?
What stresses or emotional factors may be present?
Has the patient experienced any significant life changes?
Does the patients snore or gasp during sleep (an indication of sleep apnea)?
If there is a bed partner, is his or her behavior distressing or disturbing?
Is the patient a shift worker?

Sleep Diary. If the patient cannot answer these questions, keeping a sleep diary is a helpful diagnostic tool. Every day for two weeks, the patient should record all sleep-related information, including responses to questions listed above described on a daily basis. A bed partner can help by adding his or her observations of the patient's sleep behavior.

Sleep Disorders Centers

A physician can recommend a sleep specialist or a sleep disorders center for patients with severe restless legs syndrome. Centers are accredited by the American Academy of Sleep Medicine. Patients should investigate centers carefully, being sure that they offer full sleep studies. [ See Where Else Can Help for Insomnia Be Obtained?, below.]

Among the signs that may indicate a need for a sleep disorders center are the following:

Insomnia due to psychologic disorders.
Sleeping problems due to substance abuse.
Snoring and sudden awakening with gasping for breath (possible sleep apnea).
Severe restless legs syndrome.
Persistent daytime sleepiness.
Sudden episodes of falling asleep during the day (possible narcolepsy).
At most, sleep disorders centers patients undergo an in-depth analysis, usually supervised by a multidisciplinary team of consultants who can provide both physical and psychiatric evaluations.

Polysomnography. Polysomnography may be used to rule out other sleep disorders. It is not useful for restless legs syndrome itself unless the physician suspects that presence of periodic limb movement. The patient arrives about two hours before bedtime without having made any changes in daily habits. The instrument electronically monitors the patient during sleep. It tracks the following:

Brain waves.
Body movements.
Breathing.
Heartbeats.

Investigative Monitors

It is often difficult to evaluate the extent of restless legs syndrome from patient self-reporting, since they may not even be aware of some of the events that occur during the night. New tools are being developed to monitor activity during sleep while the patient is at home.

Actigraph. A new device, the actigraph, can be worn on the wrist. It records body movements during wakefulness and sleep. It can be used at home and therefore is reflects more natural conditions than tests in a laboratory. It can also keep a record over several nights rather than a single session. However, it cannot distinguish whether the patient is awake or asleep.

BodyTrac. R esearchers are looking at a new device called BodyTrac, which monitors and stores behavioral sleep-related events in sleepwalkers. So far, BodyTrac is very accurate in evaluating a variety of sleep disturbances, like RLS, not likely to be recalled by the sleeper. More research is needed.

WHAT ARE THE NONMEDICAL TREATMENTS FOR RESTLESS LEGS SYNDROME?

The initial approach to a patient who complains of sleeplessness and restless legs syndrome is a non-drug one that aims at improving sleep and eliminating possible causes of RLS. A nondrug approach is particularly an important first step in elderly patients:

A physician should first try to treat any underlying medical condition that may be causing restless legs.
If medications may be causing RLS, the physician should try to prescribe alternatives, if possible.
If the cause cannot be determined, it is best to try sleep hygiene and relaxation methods described below.
Hot baths or cold compresses may help.
Some patients report that symptoms don't occur if they sleep late in the morning, so, if feasible, changing sleep patterns may be helpful.

This approach provides added benefits, even if drug therapy is later required.

Exercise

Exercise may be one of the best ways to achieve healthy sleep. A study found that people who engaged in brisk walking for 30 minutes, four times a week, improved minor sleep disturbances after four months. Another study reported that sleep improved in a group of elderly people who exercised regularly. Regular, moderate exercise, healthful in any case, may help prevent RLS. Patients report that either bursts of excessive energy or long sedentary periods worsen symptoms.

Behavioral Approaches for Preventing Insomnia

Prevention of sleeplessness is very much dependent upon the patient's ability to relax and learn the art of sleeping well. A number of behavioral methods are aimed at achieving these goals. Behavioral methods are effective and work better than drugs in all age groups, including elderly patients. Studies have reported that between 70% and 80% of those who are treated with non-drug methods experience improved sleep with an average treatment duration of only five hours over a four-week period. Furthermore, studies report that 75% of those who have been taking drugs are able to stop or reduce their use.

Experts currently recommend the following methods in order of effectiveness for patients with chronic primary insomnia. Some may be helpful for patients with sleeplessness due to RLS:

Stimulus control (standard treatment, which receives a high degree of physician support). It may also be helpful for some patients with secondary insomnia caused by a medical or psychiatric condition.
Progressive muscle relaxation (studies and physician reports reflect a moderate degree of confidence in its effectiveness). It may also be helpful for some patients with secondary insomnia caused by a medical or psychiatric condition.
Paradoxical intention (studies and physician reports reflect a moderate degree of certainty in its effectiveness).
Biofeedback (studies and physician reports reflect a moderate degree of certainty in its effectiveness).
Sleep restriction (evidence inconclusive on its value).
Multicomponent cognitive behavioral therapy (evidence is inconclusive on its value, although a 2001 study reported that it was significantly more effective that progressive muscle relaxation and offered persistent benefits).
Sleep hygiene, imagery training, and cognitive training only (experts unable to recommend these approaches as sole therapy).

Stimulus Control. Stimulus control is now considered the standard treatment for primary chronic insomnia and may be helpful for some patients with secondary insomnia as well. The primary goal of stimulus control is to regain the idea that the bed is for sleeping. It involves the following:

Go to bed only when ready to sleep or for sex.
If unable to sleep within fifteen to twenty minutes, get up and go into another room. (People who find it physically difficult to get out of bed may stay in bed, but they should do something relatively arousing, such as reading.)
Maintain a regular wake-up time no matter how few hours are spent sleeping.
Avoid naps.

Progressive Muscle Relaxation. Progressive muscle relaxation is another effective technique for inducing sleep and may help reduce legs symptoms in some patients.

It takes about 10 minutes a day and involves the following:

Focus on a specific muscle group (for example the muscle in the right foot).
Inhale and tense the muscle group for about eight seconds until the muscles start to shake and there is some mild muscle pain. (Do this gently. It is not intended to cause any severe muscles contraction pain.)
Release the muscles quickly and let them become loose and limp. Stay relaxed for 15 seconds and then repeat the same muscle group.
Focus on the next muscle group and repeat the sequence. (Typically start with the muscles in one foot and move progressively from each foot and leg up through the abdomen, chest, then to each hand and arm and then to the neck and shoulders and face.)

Paradoxical Intention. Paradoxical intention is a psychological approach that is based on doing the opposite of what one wants or fears and take it to extreme. The first step is to make a plan to take such a paradoxical approach to RLS.

Instead of going through activities leading to sleep, the patient prepares for staying awake and doing something energetic.
In some cases, people may take specific psychological barriers to sleep to an extreme limit. For example, if worry is a factor in RLS, the patient intensifies the worries.

Biofeedback. Biofeedback is also effective but requires being monitored with an electroencephalogram (EEG), a device that measures brain waves. Patients are given feedback to recognize certain states of tension or sleep stages so that they can either avoid or repeat them voluntarily.

Sleep Restriction Therapy. Sleep restriction therapy may be effective, although evidence is inconclusive. In one 2001 study, patients practiced sleep hygiene and sleep restriction. Sleep hygiene was very helpful during the first two months while sleep restriction led to sustained benefits and deeper sleep. The approach is a systematic method for achieving sleep and restricting the time spent in bed.

The first step is to calculate a person's sleep efficiency number :

Keep a sleep diary for two weeks.
Dividing actual average nightly sleep time by hours in bed. The answer, given as a percentage, is the sleep efficiency number. (For example, if a patient sleeps five hours out of seven hours in bed the calculation result is .714 and the sleep efficiency percentage is 71%.)
The patient's goal is to achieve a sleep efficiency percentage of between 85% and 90%, which means only 10% to 15% of the time is spent staying awake in bed. (Sleep efficiency in older people may fall somewhere between 75% to 85%.)

To achieve this goal, the patient takes the following actions:

Begin by going to bed fifteen minutes later than usual the first week.
If 85% sleep efficiency isn't reached by the end of the week, another fifteen minutes is added to staying up until bedtime.
The patient must limit time in bed even when tired. (The time in bed should not be reduced below five hours, however.)
Once efficiency reaches 90% or more, the time allowed in bed is increased by 15 minutes per week.

Other parts of the program include stopping any sleep medications and following good sleep hygiene. [ See Box Sleep Hygiene Tips.]

People using this treatment have reported lasting improvements after just eight weeks. In one study comparing those who used sleep restriction therapy and those who used relaxation techniques, the improvement for sleep restriction subjects was approximately twice that of those who used relaxation methods alone.

Cognitive-Behavioral Therapy. Cognitive behavioral therapy (CBT) is a form of therapy that emphasizes observing and changing negative thoughts (such as, "I'll never fall asleep"). It also employs actions intended to change behavior. Studies have been mixed on its effectiveness. One reported that it helped people with insomnia, even when it was caused by pain disorders, which are commonly thought to require sleeping medications and be resistant to therapeutic maneuvers.

Sleep Hygiene. The term sleep hygiene is used to describe simple behaviors that may help everyone improve their sleep. [ See Box Sleep Hygiene Tips.]

Sleep Hygiene Tips

Establish a regular time for going to bed and getting up in the morning and stick to it even on weekends and during vacations.
Use the bed for sleep and sexual relations only, not for reading, watching television, or working; excessive time in bed seems to fragment sleep.
Avoid naps, especially in the evening.
Exercise before dinner. A low point in energy occurs a few hours after exercise; sleep will then come more easily. Exercising close to bedtime, however, may increase alertness.
Take a hot bath about an hour and a half to two hours before bedtime. This alters the body's core temperature rhythm and helps people fall asleep more easily and more continuously. (Taking a bath shortly before bed increases alertness.)
Do something relaxing in the half-hour before bedtime. Reading, meditation, and a leisurely walk are all appropriate activities.
Keep the bedroom relatively cool and well ventilated.
Do not look at the clock. Obsessing over time will just make it more difficult to sleep.
A light snack before bedtime can help sleep, but a large meal may have the opposite effect.
Eat light meals and schedule dinner four to five hours before bedtime.
Spend a half hour in the sun each day. (Take precautions against overexposure to sunlight by wearing protective clothing and sunscreen. The best times are early or late in the day.)
Avoid fluids just before bedtime so that sleep is not disturbed by the need to urinate.
Avoid caffeine in the hours before sleep.
Quitting smoking not only brings many health benefits to any smoker, it eliminates the effects of nicotine that contribute to sleep loss.
Patients who cannot sleep after 15 or 20 minutes should get up and go into another room, read or do a quiet activity using dim lighting until they are sleepy again. (Don't watch television, for it emits too bright a light.)
One study showed that sleeping alone is more restful than sleeping with another person. If a person with insomnia is distracted by a sleeping bed partner, moving to the couch for a couple of nights might be useful.

WHAT ARE THE MEDICATIONS FOR RESTLESS LEGS SYNDROME?

The American Academy of Sleep Medicine recommends medications only for persons who fulfill certain diagnostic criteria, and who experience excessive sleepiness that occurs secondary to RLS or periodic limb movement disorder. Little is known about the best way to treat RLS but some experts suggest the following:

Over-the-counter pain relievers and possibly mineral and vitamin supplements (particularly folic acid in people who might be deficient) should be tried first.
People who are iron deficient might try oral iron supplements.
The best-studied medications are dopaminergic agents (drugs that increase levels of dopamine) are the standard agents to date for treating severe RLS.
If dopaminergic agents failed, other agents tried include opioids, benzodiazepines (anti-anxiety drugs), and anticonvulsants.

Over-the Counter Drugs and Supplements

NSAIDs. Before taking stronger medications, people should try over-the-counter pain relievers, such as acetaminophen (Tylenol) or nonsteroidal anti-inflammatory drugs (NSAIDs), which include ibuprofen (Advil, Motrin, Rufen), naproxen (Anaprox, Naprosyn, Aleve), and ketoprofen (Orudis KT, Aktron).

Over-the Counter Supplements. The following supplements may have some benefit:

Some people report that vitamin E (800 to 1200 IU per day) may help.
Calcium, magnesium, or potassium supplements have helped some people.
People who have folate deficiencies should take supplements of folic acid. This is particularly important during pregnancy, when folate deficiencies have been associated with RLS. (And, more importantly, deficiencies also increase the risk for birth defects in the infant.)

Iron Supplements

Iron supplements can produce a significant reduction in symptoms in people with RLS who are iron deficient. They do not appear to have much value for RLS patients with normal or above normal levels. To replace iron, the preferred form of iron tablets are ferrous salts, usually ferrous sulfate (Feosol, Fer-In-Sol, Mol-Iron). Other forms include ferrous fumarate (Femiron, FerroSequels, Feostat, Fumerin, Hemocyte, Ircon), ferrous gluconate (Fergon, Ferralet, Simron), polysaccharide-iron complex (Niferex, Nu-Iron), and carbonyl iron (Elemental Iron, Feosol Caplet, Ferra-Cap). Specific brands and forms may have certain advantages. The following are some examples:

Prolonged-release ferrous sulfate (Slow Fe) may enhance iron absorption with fewer side effects than standard ferrous sulfate pills.
FerroSequels contains a stool softener, which helps prevent constipation.
Polysaccharide-iron complex has fewer side effects than and has equal absorption rates to ferrous salts. It is very expensive, however.
Carbonyl iron is composed of very fine tiny uniform spheres of iron powder and may prove to be less toxic than ferrous iron.
Coated or combination pills do not appear to offer any additional advantages and may hinder absorption of the iron.

Regimen. The general guidelines for iron replacement are as follows:

For adults, physicians usually advise one ferrous sulfate tablet three times a day. No one should take a double dose of iron if one is missed. As few as three adult iron tablets can poison children, even fatally. This includes any form of iron pill.

Other tips for taking iron are as follows:

For best absorption, iron should be taken between meals. (Iron may cause stomach and intestinal disturbances, however, and some experts believe that low doses of ferrous sulfate can be taken with food and absorbed without side effects.)
One should always drink a full eight ounces of fluid with an iron pill.
Tablets should be kept in a cool place. (Bathroom medicine cabinets may be too warm and humid, which may cause the pills to disintegrate.)
One study suggested that iron supplements impeded the absorption of non-heme iron (found in legumes and other vegetables) but not heme iron (contained in meat).

Side Effects. Common side effects of iron supplements include the following:

Constipation and diarrhea are very common. They are rarely severe, although iron tablets can aggravate existing gastrointestinal problems such as ulcers and ulcerative colitis.
Nausea and vomiting may occur with high doses, but can be controlled by taking smaller amounts. Switching to ferrous gluconate may help some people with severe gastrointestinal problems.
Black stools are normal when taking iron tablets. In fact, if they do not turn black, the tablets may not be working effectively. This tends to be a more common problem with coated or long-acting iron tablets.
If the stools are tarry looking as well as black, if they have red streaks, or if cramps, sharp pains, or soreness in the stomach occur, gastrointestinal bleeding may be causing the iron deficiency and the patient should call the physician promptly.
Acute iron poisoning is rare in adults but can be fatal in children who take adult-strength tablets.

Interactions with Other Drugs. Importantly, iron supplements may reduce the effectiveness of the anti-Parkinson's Disease drugs methyldopa, levodopa, and carbidopa, which are often taken for severe RLS. Iron tablets may also reduce the effectiveness of other drugs, including antacids and the antibiotics tetracycline, penicillamine, and ciprofloxacin. At least two hours should elapse between doses of these drugs and iron supplements.

Supplementary Agents. Adding either ascorbic acid (vitamin C) or succinic acid to ferrous sulfate therapy will improve absorption of iron stores. Ascorbic acid added to iron therapy, however, may exacerbate some of the side effects. Succinic acid added to ferrous sulfate does not appear to increase side effects. Some studies have found that the addition of zinc to iron supplements increases hemoglobin levels more than iron alone. One study of pregnant women suggested that zinc affects a hormone called insulin-like growth factor-I (IGF-I), which plays a role in the regulation of red blood cell production.

Levodopa and Other Dopaminergic Agents

Medications called dopaminergic agents increase the availability of the brain chemical dopamine and are the standard agents used for severe RLS. These drugs significantly reduce the number of periodic limb movements per hour and improve the subjective quality of sleep. Such drugs are ordinarily used for Parkinson's disease, and can have severe side effects.

Levodopa. The drug levodopa (L-dopa) is the agent most often used for severe RLS. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America. (Levodopa combinations are shown to be well tolerated and safe.) Levodopa has a rapid onset of action, and effectiveness is usually achieved within the first few days of therapy. One study reported that a combination therapy of regular-release L-dopa plus sustained release L-dopa was effective in improving sleep. About 25% of patients who take Sinemet report a rebound effect, with increased leg movements not only in the morning as the dose wears off, but in late afternoon as well. Using the lowest dose possible can minimize this effect.

Dopaminergic Receptor Agonists. Agents known as dopamine receptor agonists may be effective alternatives to L-dopa and have fewer side effects. They include Pergolide (Permax), pramipexole (Mirapex), ropinirole (Requip), cabergoline (Dostinex), and tolpicone (Tasmar). Studies on some of these agents report the following:

Pergolide is as effective Sinemet with fewer side effects and the benefits persist for at least a year. Nausea and nasal congestion are common, however. Adding the drug domperidone helps relieve nausea.
To date, pramipexole is the most potent drug yet used for RLS and has resulted in dramatic improvement in symptoms. It seems to be very effective in improving sleep and may also reduce periodic limb movement. A long-term, follow up study showed the drug continued to be effective for RLS, even after seven months of use. Pramipexole also appears to have antidepressant properties. The drug is used at much lower doses than when used for Parkinson's disease, so severe long-term side effects are rare.
Cabergoline (Dostinex), another dopamine agonist, is also showing promise. In the study, cabergoline was used for RLS after levodopa had either failed or resulted in increased symptoms. Patients in the study reported relief or freedom from symptoms after four weeks of use.

Side effects of all these agents include nausea, nasal congestion, dizziness, headache, diarrhea, and vertigo. More research is needed.

Side effects of all these drugs vary, but generally include nausea, constipation, headache, rapid heartbeat, and nasal congestion. In rare cases, they can cause hallucinations.

Benzodiazepines

Benzodiazepines, such as clonazepam (Klonopin), are commonly called hypnotics and are used for insomnia and anxiety. They have also proven to be helpful for some patients with severe RLS. Clonazepam (Klonopin) may be particularly helpful for children with both periodic limb movement and symptoms of attention-deficit hyperactivity disorder.

Side Effects. Elderly people are more susceptible to side effects and should usually start at half the dose prescribed for younger people and should not take long-acting forms. Side effects may differ depending on whether the benzodiazepine is long- or shorting acting. They include the following:

The drugs may increase depression, a common co-condition in any case in many people with insomnia.
Respiratory depression may occur with overuse or with people with pre-existing respiratory illness.
Long-acting agents have a very high rate of residual daytime drowsiness compared to others. They have been associated with a significantly increased risk for automobile accidents and falls in the elderly particularly in the first week after taking them. Shorter-acting benzodiazepines do not appear to pose as high a risk.
Memory loss (so-called traveler's amnesia), sleepwalking, and odd mood states have been reported after taking Halcion and other short-acting benzodiazepines. These effects are rare and probably enhanced by alcohol.
Because these drugs cross the placenta and enter breast milk, pregnant nursing women should not use them. An association was reported between the use of benzodiazepines in the first trimester of pregnancy and the development of cleft lip in newborns.
In rare cases, overdoses have been fatal.

Interactions. Benzodiazepines are potentially dangerous when used in combination with alcohol, and some medications, like the ulcer medication cimetidine, can slow the metabolism of the benzodiazepine.

Withdrawal Symptoms. Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last one to three weeks after stopping the drug and may include the following:

Gastrointestinal distress.
Sweating.
Disturbed heart rhythm.
In severe cases, patients might hallucinate or experience seizures, even a week or more after the drug has been stopped.

Rebound Insomnia. Rebound insomnia, which often occurs after withdrawal, typically includes one to two nights of sleep disturbance, daytime sleepiness, and anxiety. The chances for rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.

Opiates

Narcotics, pain-relieving and sleep-inducing drugs that act on the central nervous system are sometimes prescribed for severe cases of RLS. There are two types of narcotics:

Opiates which are derived from natural opium (eg, morphine and codeine).
Opioids, which are synthetic drugs (eg, oxycodone, tramadol).

Examples used for RLS include the following:

Some patients report relief with the use of the opiate fentanyl (Duragesic), used in skin patch form.
Apomorphine is a morphine derivative. In one study, it was administered subcutaneously (under the skin) at night and reduced nocturnal discomfort and leg movements in some patients.
Tramadol (Ultram) was very effective for RLS with few or no side effects in one small study. It has fewer adverse effects than other narcotics and has specific properties that make dependency unlikely. Nevertheless, withdrawal after long-term use (eg, over a year) can cause intense symptoms, including diarrhea, insomnia, and even restless legs syndrome it self.

Although the use of narcotics for severe RLS is controversial, many studies have suggested that they are rarely addictive for pain sufferers except among patients with a history of substance abuse. The use of such agents may be beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse and then regularly monitoring those who are taking it, adjusting the dose as necessary to achieve an acceptable balance between pain relief and side effects.

Note: Of great concern are media reports of abuse from illegal sales of oxycodone (Percodan, Percocet, Roxicodone, Oxycontin), a very effective pain killer. Such reports may cause unwarranted fear of addiction in chronic pain sufferers who might benefit from tramadol.

Antiseizure Agents

The antiseizure drugs, such as gabapentin (Neurontin), valproic acid (Depakene), and carbamazepine (Tegretol), relax blood vessels and are being tested for RLS. Gabapentin, a newer antiseizure drug, is showing particular promise for mild to moderate RLS. A small study showed gabapentin was also effective in some hemodialysis patients with RLS.

Side Effects. All antiseizure agents have potentially severe side effects and should be tried only after non-drug methods have failed. Side effects of many anti-seizure agents include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and loss (taking zinc and selenium supplements may help reduce this effect). Some can also cause birth defects and, in rare cases, liver toxicity. Gabapentin may have fewer of these side effects than valproic acid or carbamazapine.

Selective Serotonin Reuptake Inhibitors (SSRIs) and Similar Agents

Although the neurotransmitter serotonin has been associated with RLS, one study found that the common antidepressants known as SSRIs, which increase serotonin in the brain, reduced RLS in 58% of patients and eliminated symptoms in 12%. Oddly, however, RLS became worse in another 12%. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa, Cipramil).

Wellbutrin (bupropion) a newer agent that has slightly different actions may also be helpful for RLS. These agents are not addictive and do not have the severe side effects of other RLS drugs, but more research is warranted.

Side Effects of SSRIs. Side effects include the following:

Nausea and gastrointestinal problems. These effects usually wear off over time.
Agitation, insomnia, mild tremor, and impulsivity occur in 10% and 20% of people who take SSRIs, these symptoms may be particularly problematic in patients who also suffer from anxiety, sleeplessness, or both. Such side effects may persist. On the other hand, about 20% of SSRI-treated patients experience drowsiness, which may be counteracted by taking the medication at bedtime.
Dry mouth is common and can increase the risk for cavities and mouth sores.
Headache.
Some weight loss during the first few weeks of treatment may occur, but over time patients on maintenance treatment typically return to their pretreatment weight.
Sexual dysfunction, including delayed or loss of orgasm and low sexual drive, occurs in 30% to 40% of patients on SSRIs and accounts for a substantial amount of noncompliance. (Citalopram, a newer SSRI, may pose a lower risk than other SSRIs for this side effect.) Taking a supervised drug "holiday" on the weekend may improve sexual function during that time. (Withdrawal symptoms may develop and include return of depression, sleep problems, exhaustion, and dizziness. Prozac, with its longer duration of action, appears to be associated with a lower risk for withdrawal symptoms than shorter-lasting SSRIs, but a weekend off this drug may not be long enough to restore sexual function.) The physician may recommend other possible strategies to circumvent sexual dysfunction, including reducing the antidepressant dosage, switching antidepressants, or adding medication to curtail the side effect.

Management of SSRI-Induced Side Effects

Elderly people taking these drugs should take the lowest dose possible, and those with heart problems should be monitored closely. Over the years, some patients taking SSRIs have reported a group of side effects, known as extrapyramidal symptoms, which are similar to those in Parkinson disease and affect the nerves and muscles controlling movement and coordination. They are uncommon and when they develop they tend to occur within the first month of treatment.
High doses or interactions with other drugs may cause hallucinations, confusion, changes in blood pressure, stiffness, and irregular heart beats. Serious interactions can occur with other antidepressants, such as tricyclics and, of particular note, MAOIs [ see below ]. Other serious interactions have occurred with Meperidine (Demerol), illegal substances, such as LSD, cocaine, or "ecstasy."
People who take SSRIs may drink alcohol in moderation, although the combination may compound any drowsiness experienced with SSRIs, and some SSRIs increase the effects of alcohol.
Death from overdose is extremely rare.

Other Agents

Clonidine (Catapres), a drug used for high blood pressure, is helpful for some patients. The anti-spasm drug baclofen (Lioresal) appears to reduce intensity but not frequency of movements.

WHAT ARE NOCTURNAL LEG CRAMPS?

Benign nocturnal leg cramps are muscle spasms in the calf (also called a charley horse). They can occur one or many times during the night, lasting from a few seconds to a few minutes. Some people experience them regularly; others only on isolated occurrences.

Causes of Nocturnal Leg Cramps

Calcium and phosphorus imbalances can cause cramping, particularly during pregnancy. Low fluid levels in the body can also result in calcium and phosphorus imbalances that can cause leg cramps. This can occur from taking diuretics, excessive perspiration, vomiting, and diarrhea. Medical causes of muscle cramping include hypothyroidism, Addison's disease, uremia, and many diseases that affect nerves and muscles. Peripheral neuropathy, a complication of diabetes in which the nerves in the extremities are impaired, which can cause painful, numb, or tingling legs.

Risk Factors for Nocturnal Leg Cramps

Nocturnal leg cramps occur at all ages but peak at different times. They occur particularly in adolescence, during pregnancy, and in old age. One study in campers reported an incidence of 7.3% in children older than eight (but not younger). This incidence increased at 12 years old and peaked at 16 to 18 years. Most adolescents with leg cramps reported that they had them one to four times per year. Pregnant women with low calcium levels due to an imbalance in calcium and phosphorus are at risk for leg cramps (such women should reduce milk intake because it does not correct this imbalance and they should take nonphosphate calcium supplements instead).

Consequences of Nocturnal Leg Cramps

Nocturnal leg cramps, like restless legs syndrome, rarely have any serious consequences. In some cases, however, severe and persistent symptoms can cause chronic insomnia and considerable mental distress.

Treatments for Nocturnal Leg Cramps

The treatments for nocturnal leg cramps are generally lifestyle changes. Everyone with leg cramps should drink plenty of water to maintain adequate fluid levels. Taking nonphosphate calcium supplements and reducing mild intake may help relieve leg cramps in pregnant women and other people who require calcium supplements. Drinking tonic soda (which contains small amounts of quinine) before bedtime may be helpful.

To prevent cramps from occurring, nightly stretching exercises may be the best preventive measures for leg cramps. And while in bed, loose covers should be used to prevent pointing the toes, which causes calf muscles to contract and cramp. Propping the feet up higher than the torso may help. Once a cramp begins, the patient should straighten the leg, flex the foot up or grab the toes and pull forward.

Medications. Drugs used for leg cramps include vitamin E and potassium chloride, but they are not very effective. Quinine had been used to prevent leg cramping, but was banned by the FDA. Studies indicate quinine had only a slight benefit. Some serious, although rare, side effects were reported, including bleeding problems and heart irregularities. Other, less serious side effects include headaches, vision problems, and rash.

WHERE ELSE CAN HELP FOR LEG DISORDERS BE OBTAINED?

American Academcy of Sleep Medicine, 6301 Bandel Road, Suite 101, Rochester, MN 55901, call (507-287-6006) or on the Internet (http://www.asda.org/)

Gives all accredited sleep disorders centers. This is a professional organization, but they will provide people with a full list of accredited Sleep Disorder Clinics. They publish the journal Sleep.

National Sleep Foundation, 1522 K Street, NW, Suite 500, Washington, DC 20005. Call (202-347-347) or (http://www.sleepfoundation.org)

Will supply names of sleep disorders clinics and information to the public.

National Center for Sleep Disorders Research, National Heart, Lung, Blood Institute, PO Box 30105, Bethesda, MD 20824-0105. Call (301-251-1222) or (http://www.nhlbi.nih.gov/health/public/sleep/index.htm)

Restless Legs Syndrome Foundation, 819 Second Street SW, Rochester, Minnesota 55902-2985 or (http://www.rls.org)

Society for Light Treatment and Biological Rhythms, PO Box 591687, 174 Cook Street. San Francisco, CA 94159-1687, or (http://www.sltbr.org/)

Useful Internet Sites

Comprehensive website on sleep disorders (http://www.sleephomepages.org/) Has a searchable database with articles on all sleep topics.

The Sleep Well (http://www.sleepquest.com/). This is a very good site filled with information

Sleep Research Online (http://www.sro.org/)