Restless legs syndrome (RLS) is a neurological disorder
characterized by unpleasant sensations in the legs and 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 and trying to relax activates the symptoms. As a result,
most people with RLS have difficulty falling asleep and staying
asleep. Left untreated, the condition causes exhaustion and daytime
fatigue. Many people with RLS report that their job, personal
relations, and activities of daily living are strongly affected as a
result of their exhaustion. They are 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 and, 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 is not 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 and for longer periods of time.
More than 80 percent 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 and 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 do not experience RLS. Like RLS, the cause of PLMD is unknown.
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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 and ankle; more rarely, they
occur in the feet, thighs, arms, and 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, and toss and turn
in bed.
Most people find the symptoms to be less noticeable during the
day and 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 and duration from person to
person. Mild RLS occurs episodically, with only mild disruption of
sleep onset, and 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 and
result in burdensome interruption of sleep and 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 is usually during the early stages
of the disorder. In general, however, symptoms become more severe
over time.
People who have both RLS and an associated condition tend to
develop more severe symptoms rapidly. In contrast, those whose RLS
is not related to any other medical condition and whose onset is at
an early age show a very slow progression of the disorder and many
years may pass before symptoms occur regularly.
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In most cases, the cause of RLS is unknown (referred to as
idiopathic). A family history of the condition is seen in
approximately 50 percent of such cases, suggesting a genetic form of
the disorder. People with familial RLS tend to be younger when
symptoms start and have a slower progression of the condition.
In other cases, RLS appears to be related to the following
factors or conditions, although researchers do not yet know if these
factors actually cause RLS.
- 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,
and 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), and some cold and allergy medications-may
aggravate symptoms. Patients can talk with their physicians about the possibility
of changing medications.
Researchers also have found that caffeine, alcohol, and tobacco
may aggravate or trigger symptoms in patients who are predisposed to
develop RLS. Some studies have shown that a reduction or complete
elimination of such substances may relieve symptoms, although it
remains unclear whether elimination of such substances can prevent
RLS symptoms from occurring at all.
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Currently, there is no single diagnostic test for RLS. The
disorder is diagnosed clinically by evaluating the patient's history
and 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 four
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 and are partially or
temporarily relieved by activity, (3) motor restlessness, and (4)
nocturnal worsening of symptoms. Although about 80 percent of those
with RLS also experience PLMD, it is not necessary for a diagnosis
of RLS. In more severe cases, patients may experience dyskinesia
(uncontrolled, often continuous movements) while awake, and 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 and jerking. The result is excessive daytime
sleepiness and 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 and information from
their medical history, including past medical problems, family
history, and current medications. Patients may be asked about
frequency, duration, and intensity of symptoms as well as their
tendency toward daytime sleep patterns and 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 and support the diagnosis of RLS. Blood tests to exclude
anemia, decreased iron stores, diabetes, and renal dysfunction
should be performed. Electromyography and nerve conduction studies
may also be recommended to measure electrical activity in muscles
and nerves, and Doppler sonography may be used to evaluate muscle
activity in the legs. Such tests can document any accompanying
damage or disease in nerves and nerve roots (such as peripheral
neuropathy and 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, and 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.
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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, and
many physicians suggest certain lifestyle changes and activities to
reduce or eliminate symptoms. Decreased use of caffeine, alcohol,
and tobacco may provide some relief. Physicians may suggest that
certain individuals take supplements to correct deficiencies in
iron, folate, and 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, and
anticonvulsants. Dopaminergic agents, largely used to treat
Parkinson's disease, have been shown to reduce RLS symptoms and PLMD
and 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, and ropinirole hydrochloride may be
effective in some patients and are less likely to cause
augmentation.
Benzodiazepines (such as clonazepam and diazepam) may be
prescribed for patients who have mild or intermittent symptoms.
These drugs help patients obtain a more restful sleep but they do
not fully alleviate RLS symptoms and can cause daytime sleepiness.
Because these depressants also may induce or aggravate sleep apnea
in some cases, they should not 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 and diminish pain. Side effects include dizziness,
nausea, vomiting, and the risk of addiction.
Anticonvulsants such as carbamazepine and gabapentin are also
useful for some patients, as they decrease the sensory disturbances
(creeping and crawling sensations). Dizziness, fatigue, and
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.
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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 and
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 does not indicate the onset of another
neurological disease.
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Within the Federal Government, the National Institute of
Neurological Disorders and Stroke (NINDS), one of the National
Institutes of Health, has primary responsibility for conducting and
supporting research on RLS. The goal of this research is to increase
scientific understanding of RLS, find improved methods of diagnosing
and treating the syndrome, and 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, and 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 and 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 and recommend
ways to advance and encourage research in this field. Participants'
recommendations for further research included the development of an
animal model of RLS; additional genetic, epidemiologic, and
pathophysiologic investigations of RLS; efforts to define genetic
and non-genetic forms of RLS; establishment of a brain tissue bank
to aid investigators; continuing investigations on dopamine and RLS;
and 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 and may
lead to a possible treatment. A recent study by NINDS-funded
researchers showed that a patient with RLS and Parkinson's disease
benefited from a pallidotomy and obtained relief from the limb
discomfort caused by RLS. Additional research must be conducted to
duplicate these results in other patients and to learn whether
pallidotomy would be effective in RLS patients who do not 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.
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Restless Legs Syndrome Foundation
National Sleep Foundation
National Heart, Lung, and Blood Institute
(NHBLI)
BRAIN
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