Restless legs syndrome (RLS) is a neurological disorder characterized by unpleasant sensations in the legs & an uncontrollable urge to move when at rest in an effort to relieve these feelings.

RLS sensations are often described by people as burning, creeping, tugging, or like insects crawling inside the legs. Often called paresthesias (abnormal sensations) or dysesthesias (unpleasant abnormal sensations), the sensations range in severity from uncomfortable to irritating to painful.

The most distinctive or unusual aspect of the condition is that lying down & trying to relax activates the symptoms. As a result, most people with RLS have difficulty falling asleep & staying asleep.

Left untreated, the condition causes exhaustion & daytime fatigue. Many people with RLS report that their job, personal relations & activities of daily living are strongly affected as a result of their exhaustion.

They're often unable to concentrate, have impaired memory, or fail to accomplish daily tasks.

Some researchers estimate that RLS affects as many as 12 million Americans. However, others estimate a much higher occurrence because RLS is thought to be underdiagnosed & in some cases, misdiagnosed.

Some people with RLS will not seek medical attention, believing that they will not be taken seriously, that their symptoms are too mild, or that their condition isn't treatable. Some physicians wrongly attribute the symptoms to nervousness, insomnia, stress, arthritis, muscle cramps, or aging.

RLS occurs in both genders, although the incidence may be slightly higher in women. Although the syndrome may begin at any age, even as early as infancy, most patients who are severely affected are middle-aged or older.

In addition, the severity of the disorder appears to increase with age. Older patients experience symptoms more frequently & for longer periods of time.

More than 80% of people with RLS also experience a more common condition known as periodic limb movement disorder (PLMD). PLMD is characterized by involuntary leg twitching or jerking movements during sleep that typically occur every 10 to 60 seconds, sometimes throughout the night.

The symptoms cause repeated awakening & severely disrupted sleep. Unlike RLS, the movements caused by PLMD are involuntary-people have no control over them. Although many patients with RLS also develop PLMD, most people with PLMD don't experience RLS. Like RLS, the cause of PLMD is unknown.

As described above, people with RLS feel uncomfortable sensations in their legs, especially when sitting or lying down, accompanied by an irresistible urge to move about. These sensations usually occur deep inside the leg, between the knee & ankle; more rarely, they occur in the feet, thighs, arms & hands. Although the sensations can occur on just one side of the body, they most often affect both sides.

Because moving the legs (or other affected parts of the body) relieves the discomfort, people with RLS often keep their legs in motion to minimize or prevent the sensations. They may pace the floor, constantly move their legs while sitting & toss & turn in bed.

Most people find the symptoms to be less noticeable during the day & more pronounced in the evening or at night, especially during the onset of sleep. For many people, the symptoms disappear by early morning, allowing for more refreshing sleep at that time.

Other triggering situations are periods of inactivity such as long car trips, sitting in a movie theater, long-distance flights, immobilization in a cast, or relaxation exercises.

The symptoms of RLS vary in severity & duration from person to person. Mild RLS occurs episodically, with only mild disruption of sleep onset & causes little distress.

In moderately severe cases, symptoms occur only once or twice a week but result in significant delay of sleep onset, with some disruption of daytime function.

In severe cases of RLS, the symptoms occur more than twice a week & result in burdensome interruption of sleep & impairment of daytime function.

Symptoms may begin at any stage of life, although the disorder is more common with increasing age. Sometimes people will experience spontaneous improvement over a period of weeks or months.

Although rare, spontaneous improvement over a period of years also can occur. If these improvements occur, it's usually during the early stages of the disorder. In general, however, symptoms become more severe over time.

People who have both RLS & an associated condition tend to develop more severe symptoms rapidly. In contrast, those whose RLS isn't related to any other medical condition & whose onset is at an early age show a very slow progression of the disorder & many years may pass before symptoms occur regularly.

• People with low iron levels or anemia may be prone to developing RLS. Once iron levels or anemia is corrected, patients may see a reduction in symptoms.

• Chronic diseases such as kidney failure, diabetes, Parkinson's disease & peripheral neuropathy are associated with RLS. Treating the underlying condition often provides relief from RLS symptoms.

• Some pregnant women experience RLS, especially in their last trimester. For most of these women, symptoms usually disappear within 4 weeks after delivery.

• Certain medications-such as antinausea drugs (prochlorperazine or metoclopramide), antiseizure drugs (phenytoin or droperidol), antipsychotic drugs (haloperidol or phenothiazine derivatives) & some cold & allergy medications-may aggravate symptoms.

Currently, there is no single diagnostic test for RLS. The disorder is diagnosed clinically by evaluating the patient's history & symptoms. Despite a clear description of clinical features, the condition is often misdiagnosed or underdiagnosed.

In 1995, the International Restless Legs Syndrome Study Group identified 4 basic criteria for diagnosing RLS:

(1) a desire to move the limbs, often associated with paresthesias or dysesthesias

(2) symptoms that are worse or present only during rest & are partially or temporarily relieved by activity

(3) motor restlessness

(4) nocturnal worsening of symptoms

Although about 80% of those with RLS also experience PLMD, it isn't necessary for a diagnosis of RLS. In more severe cases, patients may experience dyskinesia (uncontrolled, often continuous movements) while awake & some experience symptoms in one or both of their arms as well as their legs.

Most people with RLS have sleep disturbances, largely because of the limb discomfort & jerking. The result is excessive daytime sleepiness & fatigue.

Despite these efforts to establish standard criteria, the clinical diagnosis of RLS is difficult to make. Physicians must rely largely on patients' descriptions of symptoms & information from their medical history, including past medical problems, family history & current medications.

Patients may be asked about frequency, duration & intensity of symptoms as well as their tendency toward daytime sleep patterns & sleepiness, disturbance of sleep, or daytime function.

If a patient's history is suggestive of RLS, laboratory tests may be performed to rule out other conditions & support the diagnosis of RLS.

Blood tests to exclude anemia, decreased iron stores, diabetes & renal dysfunction should be performed. Electromyography & nerve conduction studies may also be recommended to measure electrical activity in muscles & nerves & Doppler sonography may be used to evaluate muscle activity in the legs.

Such tests can document any accompanying damage or disease in nerves & nerve roots (such as peripheral neuropathy & radiculopathy) or other leg-related movement disorders.

Negative results from tests may indicate that the diagnosis is RLS. In some cases, sleep studies such as polysomnography (a test that records the patient's brain waves, heartbeat & breathing during an entire night) are undertaken to identify the presence of PLMD.

The diagnosis is especially difficult with children because the physician relies heavily on the patient's explanations of symptoms, which, given the nature of the symptoms of RLS, can be difficult for a child to describe.

The syndrome can sometimes be misdiagnosed as "growing pains" or attention deficit disorder.

Although movement brings relief to those with RLS, it is generally only temporary. However, RLS can be controlled by finding any possible underlying disorder.

Often, treating the associated medical condition, such as peripheral neuropathy or diabetes, will alleviate many symptoms. For patients with idiopathic RLS, treatment is directed toward relieving symptoms.

For those with mild to moderate symptoms, prevention is key & many physicians suggest certain lifestyle changes & activities to reduce or eliminate symptoms.

Decreased use of caffeine, alcohol & tobacco may provide some relief. Physicians may suggest that certain individuals take supplements to correct deficiencies in iron, folate & magnesium.

Studies also have shown that maintaining a regular sleep pattern can reduce symptoms. Some individuals, finding that RLS symptoms are minimized in the early morning, change their sleep patterns.

Others have found that a program of regular moderate exercise helps them sleep better; on the other hand, excessive exercise has been reported by some patients to aggravate RLS symptoms.

Taking a hot bath, massaging the legs, or using a heating pad or ice pack can help relieve symptoms in some patients. Although many patients find some relief with such measures, rarely do these efforts completely eliminate symptoms

Physicians also may suggest a variety of medications to treat RLS. Generally, physicians choose from dopaminergics, benzodiazepines (central nervous system depressants), opioids & anticonvulsants.

Dopaminergic agents, largely used to treat Parkinson's disease, have been shown to reduce RLS symptoms & PLMD & are considered the initial treatment of choice.

Good short-term results of treatment with levodopa plus carbidopa have been reported, although most patients eventually will develop augmentation, meaning that symptoms are reduced at night but begin to develop earlier in the day than usual.

Dopamine agonists such as pergolide mesylate, pramipexole & ropinirole hydrochloride may be effective in some patients & are less likely to cause augmentation.

In 2005, ropinirole became the only drug approved by the U.S. Food and Drug Administration specifically for the treatment of moderate to severe RLS. The drug was first approved in 1997 for patients with Parkinson’s disease.

Benzodiazepines (such as clonazepam & diazepam) may be prescribed for patients who have mild or intermittent symptoms. These drugs help patients obtain a more restful sleep but they don't fully alleviate RLS symptoms & can cause daytime sleepiness.

Because these depressants also may induce or aggravate sleep apnea in some cases, they shouldn't be used in people with this condition.

For more severe symptoms, opioids such as codeine, propoxyphene, or oxycodone may be prescribed for their ability to induce relaxation & diminish pain. Side effects include dizziness, nausea, vomiting & the risk of addiction.

Anticonvulsants such as carbamazepine & gabapentin are also useful for some patients, as they decrease the sensory disturbances (creeping & crawling sensations). Dizziness, fatigue & sleepiness are among the possible side effects.

Unfortunately, no one drug is effective for everyone with RLS. What may be helpful to one individual may actually worsen symptoms for another. In addition, medications taken regularly may lose their effect, making it necessary to change medications periodically.

RLS is generally a lifelong condition for which there is no cure. Symptoms may gradually worsen with age, though more slowly for those with the idiopathic form of RLS than for patients who also suffer from an associated medical condition.

Nevertheless, current therapies can control the disorder, minimizing symptoms & increasing periods of restful sleep.

In addition, some patients have remissions, periods in which symptoms decrease or disappear for days, weeks, or months, although symptoms usually eventually reappear.

A diagnosis of RLS doesn't indicate the onset of another neurological disease.

Within the Federal Government, the National Institute of Neurological Disorders & Stroke (NINDS), one of the National Institutes of Health, has primary responsibility for conducting & supporting research on RLS.

The goal of this research is to increase scientific understanding of RLS, find improved methods of diagnosing & treating the syndrome & discover ways to prevent it.

NINDS-supported researchers are investigating the possible role of dopamine function in RLS. Dopamine is a chemical messenger responsible for transmitting signals between one area of the brain, the substantia nigra & the next relay station of the brain, the corpus striatum, to produce smooth, purposeful muscle activity.

Researchers suspect that impaired transmission of dopamine signals may play a role in RLS. Additional research should provide new information about how RLS occurs & may help investigators identify more successful treatment options.

The NINDS sponsored a workshop on dopamine in 1999 to help plan a course for future research on disorders such as RLS & recommend ways to advance & encourage research in this field.

Participants' recommendations for further research included the development of an animal model of RLS; additional genetic, epidemiologic & pathophysiologic investigations of RLS; efforts to define genetic & non-genetic forms of RLS; establishment of a brain tissue bank to aid investigators; continuing investigations on dopamine & RLS & studies of PLMD as it relates to RLS.

Research on pallidotomy, a surgical procedure in which a portion of the brain called the globus pallidus is lesioned, may contribute to a greater understanding of the pathophysiology of RLS & may lead to a possible treatment.

A recent study by NINDS-funded researchers showed that a patient with RLS & Parkinson's disease benefited from a pallidotomy & obtained relief from the limb discomfort caused by RLS.

Additional research must be conducted to duplicate these results in other patients & to learn whether pallidotomy would be effective in RLS patients who don't also have Parkinson's disease.

In other related research, NINDS scientists are conducting studies with patients to better understand the physiological mechanisms of PLMD associated with RLS.