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Restless legs syndrome

 
Medical Encyclopedia: Restless Legs Syndrome
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Definition

Restless legs syndrome (RLS) is characterized by unpleasant sensations in the limbs, usually the legs, that occur at rest or before sleep and are relieved by activity such as walking. These sensations are felt deep within the legs and are described as creeping, crawling, aching, or fidgety.

Description

Restless legs syndrome, also known as Ekbom syndrome, Wittmaack-Ekbom syndrome, anxietas tibiarum, or anxietas tibialis, affects up to 10–15% of the population. Some studies show that RLS is more common among elderly people. Almost half of patients over age 60 who complain of insomnia are diagnosed with RLS. In some cases, the patient has another medical condition with which RLS is associated. In idiopathic RLS, no cause can be found. In familial cases, RLS may be inherited from a close relative, most likely a parent.

— Ann M. Haren


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Sci-Tech Dictionary: restless legs syndrome
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(′rest·ləs ′legz ′sin′drōm)

(medicine) A condition that is characterized by intense disagreeable feelings in the legs at rest and repose with compulsion to move the legs to get relief from these symptoms, peak onset usually occurs during middle age, and the disorder tends to become more severe with age.

Neurological Disorder:

Restless legs syndrome

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Definition

Restless legs syndrome (RLS) is a neurological disorder characterized by uncomfortable sensations in the legs and, less commonly, the arms. These sensations are exacerbated (heightened) when the person with RLS is at rest. The sensations are described as crawly, tingly, prickly and occasionally painful. They result in a nearly insuppressible urge to move around. Symptoms are often associated with sleep disturbances.

Description

Restless legs syndrome is a sensory-motor disorder that causes uncomfortable feelings in the legs, especially during periods of inactivity. Some people also report sensations in the arms, but this occurs much more rarely. The sensations occur deep in the legs and are usually described with terms that imply movement such as prickly, creepy-crawly, boring, itching, achy, pulling, tugging and painful. The symptoms result in an irrepressible urge to move the leg and are relieved when the person suffering from RLS voluntarily moves. Symptoms tend to be worse in the evening or at night.

Restless legs syndrome is associated with another disorder called periodic limb movements in sleep (PLMS). It is estimated that four out of five patients with RLS also suffer from PLMS. PLMS is characterized by jerking leg movements while sleeping that may occur as frequently as every 20 seconds. These jerks disrupt sleep by causing continual arousals throughout the night.

People with both RLS and PLMS are prone to abnormal levels of exhaustion during the day because they are unable to sleep properly at night. They may have trouble concentrating at work, at school or during social activities. They may also have mood swings and difficulty with interpersonal relationships. Depression and anxiety may also result from the lack of sleep. RLS affects people who want to travel or attend events that require sitting for long periods of time.

Demographics

As much as 10% of the population of the United States and Europe may suffer from some degree of restless legs syndrome. Fewer cases are indicated in India, Japan and Singapore, suggesting racial or ethnic factors play a role in the disorder. Although the demographics can vary greatly, the majority of people suffering from RLS are female. The age of onset also varies greatly, but the number of people suffering from RLS increases with age. However, many people with RLS report that they had symptoms of the disorder in their childhood. These symptoms were often disregarded as growing pains or hyperactivity.

Causes and symptoms

Restless legs syndrome is categorized in two ways. Primary RLS occurs in the absence of other medical symptoms, while secondary RLS is usually associated with some other medical disorder. Although the cause of primary RLS is currently unknown, a large amount of research into the cause of RLS is taking place. Researchers at Johns Hopkins University published a study in July 2003 suggesting that iron deficiencies may be related to the disorder. They dissected brains from cadavers of people who suffered from RLS and found that the cells in the midbrain were not receiving enough iron. Other researchers suggest that RLS may be related to a chemical imbalance of the neurotransmitter dopamine in the brain. There is also evidence that RLS has a genetic component. RLS occurs three to five times more frequently in an immediate family member of someone who has RLS than in the general population. A site on a chromosome that may contain a gene for RLS has been identified by molecular biologists.

In many people, other medical conditions play a role in RLS and the disorder is therefore termed secondary RLS. People with peripheral neuropathies (injury to nerves in the arms and legs) may experience RLS. Such neuropathies may result from diabetes or alcoholism. Other chronic diseases such as kidney disorders and rheumatoid arthritis may result in RLS. Iron deficiencies and blood anemias are often associated with RLS and symptoms of the disease usually decrease once blood iron levels have been corrected. Attention deficit/hyperactivity disorder has also been implicated in RLS. Pregnant women often suffer from RLS, especially in the third trimester. Some people find that high levels of caffeine intake may result in RLS.

The symptoms of RLS are all associated with unpleasant feelings in the limbs. The words used to describe these feelings are various, but include such adjectives as deep-seated crawling, jittery, tingling, burning, aching, pulling, painful, itchy or prickly. They are usually not described as a muscle cramp or numbness. Most often the sensations occur during periods of inactivity. They are characterized by an urge to get up and move. Such movements include stretching, walking, jogging or simply jiggling the legs. The feelings worsen in the evening.

A variety of symptoms are associated with RLS, but may not be characteristic of every case. Some people with RLS report involuntary arm and leg movements during the night. Others have difficulty falling asleep and are sleepy or fatigued during the day. Many people with RLS have leg discomfort that is not explained by routine medical exams.

Diagnosis

Restless legs syndrome cannot currently be diagnosed using any laboratory tests or via a routine physical examination. Diagnosis is based on information given to a doctor by the patient regarding his or her symptoms. Usually the doctor takes a complete medical history as well as a family history. The International Restless Legs Syndrome Study group has proposed a set of criteria that can be used while taking a medical history in order to diagnose RLS:

  • a compelling urge to move the arms and legs
  • restlessness that manifests itself in pacing, tossing and turning and/or rubbing the legs
  • symptoms that worsen when the patient is resting and are relieved when the patient is active
  • symptoms that worsen at the end of the day

In addition, a physical examination will be made to identify if there are any other medical conditions, such as neurological disorders or blood disorders that may be causing secondary RLS. A doctor who suspects a patient has RLS may suggest that the person spend the night in a sleep clinic to determine whether the patient also suffers from PLMS.

Treatment

Treatment for restless legs syndrome is generally twopronged, consisting of making lifestyle changes and using medications to relieve some of the symptoms. Lifestyle changes involve making changes to the diet, exercising and performing other self-directed activities, and practicing good sleep hygiene. Although the United States Food and Drug Administration has not yet approved any drugs for treating RLS, four classes of pharmaceuticals have been found effective for treating RLS: dopaminergic agents, benzodiazepines, opioids and anticonvulsants.

Lifestyle changes

Simple changes to the diet have proven effective for some people suffering from RLS. Vitamin deficiencies are a common problem in RLA patients. In patients with RLS, most physicians will check the levels of blood serum ferritin, which can indicate low iron storage. If these levels are below 50 mcg/L, then supplemental iron should be added to the diet. Other physicians have found that supplements of vitamin E, folic acid and B vitamins, and magnesium provide relief to symptoms or RLS. Reducing or eliminating caffeine and alcohol consumption has been effective in other patients.

Many who suffer from RLS find that exercise and massage help reduce symptoms. Walking or stretching before bed, taking a hot bath and using massage or acupressure help improve sleep. Practicing relaxation techniques such as mediation, yoga and biofeedback have also been found to be useful.

Good sleep hygiene includes having a restful, cool sleep environment and sleeping during consistent hours every night. Often people who suffer from RLS find that going to sleep later at night and sleeping later into the morning result in a better sleep.

Pharmaceuticals

Dopaminergic agents are the first type of drug prescribed in the treatment of RLS. Most commonly doctors prescribe dopamine-receptor agonists that are used to treat Parkinson's disease such as Mirapex (pramipexole), Permax (pergolide) and Requip (ropinirole). Sinemet (carbidopa/levodopa), which is a drug that adds dopamine to the nervous system, is also commonly prescribed. Sinemet has been used the more frequently than other drugs in treating RLS, but recently a problem known as augmentation has been associated with its use. When augmentation develops, symptoms of RLS will return earlier in the day and increasing the dose will not improve the symptoms.

Benzodiazepines are drugs that sedate and are typically taken before bedtime so that a patient with RLS can sleep more soundly. The most commonly prescribed sedative in RLS is Klonopin (clonazepam).

Opioids are synthetic narcotics that relieve pain and cause drowsiness. They are usually taken in the evening. The most commonly used opioids prescribed for RLS include Darvon or Darvocet (propoxyphene), Dolophine (methadone), Percocet (oxycodone), Ultram (Tramadol) and Vicodin (hydrocodone). One danger associated with opioids is that they can be addicting.

Anticonvulsants are drugs that were developed to prevent seizures in patients with epilepsy and stroke. Some RLS patients who report pain in their limbs have reported that these drugs, particularly Gabapentin (neurontin), are useful for relieving symptoms.

A few drugs have been found to worsen symptoms of RLS and they should be avoided by patients exhibiting RLS symptoms. These include anti-nausea drugs such as Antivert, Atarax, Compazine and Phenergan. Calcium channel blockers that are often used to treat heart conditions should be avoided. In addition, most anti-depressants tend to exacerbate symptoms of RLS. Finally, antihistamines such as Benadryl have been found to aggravate RLS symptoms in some people.

Clinical trials

A broad spectrum of clinical trials are currently underway to study RLS. The Restless Legs Syndrome Foundation maintains a website that lists a variety of studies throughout the United States that are currently recruiting volunteers. The studies test the effects of a variety of treatments including intravenous iron supplements, exercise and sleeping aids on RLS. More information can be found at .

The National Institutes of Health support three clinical trials to gain information about RLS. The first study investigates the effects of the drug Ropinirole, a dopamine-receptor agonist, on spinal cord reflexes and on symptoms of restless legs syndrome. A second study is testing whether or not sensorimotor gating (the brain's ability to filter multiple stimuli) is deficient in patients who suffer from RLS. The goal of the third study is to improve understanding of neurological conditions associated with RLS by taking careful histories and following the treatment provided by primary car physicians. Information on all three trials can be found at or by calling the Patient Recruitment and Public Liaison Office at 1-800-411-1222 or sending an electronic message to prpl@mail.cc.nih.gov.

Prognosis

RLS is usually compatible with an active, healthy life when symptoms are controlled and nutritional deficits are corrected.

Resources

BOOKS

Cunningham, Chet. Stopping Restless Legs Syndrome. United Research Publishers, 2000.

OTHER

"Do You have Restless Legs Syndrome?" Restless Leg Syndrome Foundation. (January 23, 2003). http://www.rls.org/frames/home_frame.htm.

"Facts about Restless Legs." National Sleep Foundation. (June 2003). http://www.sleepfoundation.org/publications/fact_rls.cfm.

"Facts About Restless Legs Syndrome (RLS)." National Heat Blood and Lung Institute. (October 1996). http://www.nhlbi.nih.gov/health/public/sleep/rls.htm.

Mayo Clinic Staff. "Restless Legs Syndrome." (July 23, 2002). http://www.mayoclinic.com/invoke.cfm?objectid=3E2E9266-6525-4125-923345C17FB0E20F.

National Institute of Neurological Disorders and Stroke. NINDS Restless Legs Syndrome Information Page. (July 1, 2001). http://www.ninds.nih.gov/health_and_medical/disorders/restless_doc.htm.

ORGANIZATIONS

RLS Foundation, Inc. 819 Second Street SW, Rochester, MN 55902. (507) 287-6465; Fax: (507) 287-6312. rlsfoundation@rls.org. http://www.rls.org.

National Center on Sleep Disorders Research (NCSDR). Two Rockledge Center, Suite 7024, 6701 Rockledge Drive, MSC 7920, Bethesda, MD 20892. (301) 435-0199; Fax: (301) 480-3451.


Juli M. Berwald, PhD


Dental Dictionary: restless legs syndrome
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n

A benign condition of unknown origin characterized by an irritating sensation of uneasiness, tiredness, and itching deep within the muscles of the legs, accompanied by twitching and sometimes pain. The only relief is walking or moving the legs.

Alternative Medicine Encyclopedia: Restless Leg Syndrome
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Definition

The condition known as restless leg syndrome (RLS) is a movement disorder caused by an irresistible urge to move the legs due to unpleasant sensations. It occurs primarily during times of relaxation, such as when the patient is trying to go to sleep.

Description

Most frequently, RLS troubles people over age 40. Almost half of patients over age 60 who complain of insomnia are diagnosed with RLS. Those who have a family history of it may have trouble with it as younger adults, or even as children. It is not usually described as painful, although some may complain of a disagreeable creeping, tugging, or aching sensation. A related condition, experienced by as many as 80% of RLS sufferers, is known as periodic limb movements of sleep (PLMS), or nocturnal myoclonus. In PLMS, jerky leg movements occur about every 20–40 seconds during sleep, and the arms may be affected as well.

Causes & Symptoms

Although RLS appears to be familial in some cases, other causes should be ruled out and treated before starting medication. Certain diseases and conditions are more highly associated with RLS. People experiencing symptoms should be examined and tested for anemia, uremia, and imbalances of electrolytes and vitamins. Renal failure is a major predisposing factor. RLS can also be associated with pregnancy. As many as one in seven women may experience it to some degree. It usually disappears after delivery, but it can recur with subsequent pregnancies or later in life.

Many medications can induce or worsen the symptoms of RLS. A prescribed medication should not be stopped without consulting a health care provider. Medications that may cause problems for some patients include some antidepressants, antihistamines, most antinausea medications, phenothiazine tranquilizers, sinemet, some calcium channel blockers used for hypertension, and a few psychiatric drugs. Patients with RLS or PLMS should have a health care provider ask whether alternative medications are available if one is prescribed that may worsen RLS symptoms.

Most sufferers of RLS experience mild symptoms. They may lie down to rest at the end of the day and, just before sleep, will experience discomfort in their legs that prompts them to stand up, massage the leg, or walk briefly. Eighty-five percent of RLS patients either have difficulty falling asleep or wake several times during the night; almost half experience daytime fatigue or sleepiness. It is common for the symptoms to be intermittent. They may disappear for several months and then return for no apparent reason. Two-thirds of patients report that their symptoms become worse with time. Some older patients claim to have had symptoms since they were in their early 20s, but were not diagnosed until their 50s. Suspected under diagnosis of RLS may be attributed to the difficulty experienced by patients in describing their symptoms. An estimated 2–15% of the population has some degree of RLS symptoms.

Diagnosis

A careful history enables the physician to distinguish RLS from similar types of disorders that cause nighttime discomfort in the limbs, such as muscle cramps, circulatory diseases, and damage to nerves that detect sensations or cause movement (peripheral neuropathy).

The most important tool the doctor has in diagnosing RLS is the history obtained from the patient. Several common medical conditions are known to either cause or to be closely associated with RLS. The doctor may link the patient's symptoms to one of these conditions, which include anemia; diabetes; disease of the spinal nerve roots (lumbosacral radiculopathy); Parkinson's disease; late-stage pregnancy; kidney failure (uremia); and complications of stomach surgery. In order to identify or eliminate such a cause, blood tests may be performed to determine the presence of serum ferritin, folate, vitamin B12, creatinine, and thyroid-stimulating hormones. The physician may also ask if symptoms are present in any close family members, since it is common for RLS to run in families and this type is sometimes more difficult to treat.

Treatment

It is likely that the best alternative therapy will combine both conventional and alternative approaches. Levodopa may be combined with a therapy that relieves pain, relaxes muscles, or focuses in general on the nervous system and the brain. Any such combined therapy that allows a reduction in dosage of levodopa is advantageous, since this approach will reduce the likelihood of unacceptable levels of drug side effects. Of course, the physician who prescribes the medication should monitor any combined therapy.

Acupuncture

Patients who also suffer from rheumatoid arthritis may especially benefit from acupuncture to relieve RLS symptoms. Acupuncture is believed to be effective in arthritis treatment and may stimulate those parts of the brain that are involved in RLS. It is also thought to benefit RLS patients who do not have rheumatoid arthritis.

Homeopathy

Homeopaths believe that disorders of the nervous system are especially important because the brain controls so many other bodily functions. The remedy is tailored to the individual patient and is based on individual symptoms as well as the general symptoms of RLS.

Reflexology

Reflexologists claim that the brain, head, and spine all respond to indirect massage of specific parts of the feet.

Nutritional Supplements

Supplementation of the diet with vitamin E, calcium, magnesium, and folic acid may be helpful for people with RLS.

Allopathic Treatment

If causes related to diet, metabolic abnormalities, and medication have been excluded or treated, therapeutic medications may be helpful. Some medications, including those mentioned above, may cause symptoms of RLS. Patients should check with a health care provider about these possible side effects, especially if symptoms first occur after starting a new medication.

In some people whose symptoms cannot be linked to a treatable associated condition, drug therapy may be necessary to provide relief and restore a normal sleep pattern. Prescription drugs that are normally used for RLS may include dopaminergic agents (such as levodopa and/or carbidopa, used to treat Parkinson's syndrome), dopamine agonists, opioids, benzodiazepines, anticonvulsants, iron (for anemic patients), and clonidine. Patient response is variable, so it is best to consult a health care provider to determine the best medication or combination regimen for the individual circumstances. Careful monitoring of side effects and good communication between patient and doctor can result in a flexible program of therapy that minimizes side effects and maximizes effectiveness.

Expected Results

RLS usually does not indicate the onset of other neurological disease. It may remain static, although two-thirds of patients get worse with time. The symptoms usually progress gradually. Treatment with dopamine agonists is effective in moderate to severe cases that may include significant PLMS. These drugs, however, produce significant side effects, including sleepiness and nausea. An individually tailored treatment plan is optimal. The prognosis is usually best if RLS symptoms are recent and can be traced to another treatable condition that is associated with RLS.

Prevention

Diet is one factor that can prevent symptoms of RLS. A helpful diet will include an adequate intake of iron and the B vitamins, especially B12 and folic acid. Strict vegetarians should take vitamin supplements to obtain sufficient vitamin B12. Ferrous gluconate may be easier on the digestive system than ferrous sulfate, if iron supplements are prescribed. Caffeine, alcohol, and nicotine use should be minimized or eliminated. Even a hot bath before bed has been shown to prevent symptoms for some sufferers.

Resources

Books

The Editors of Time-Life Books. The Medical Advisor. The Complete Guide to Conventional and Alternative Medicine. Alexandria, VA: Time-Life Books, 1997.

Long, James W., and James J. Rybacki. The Essential Guide to Prescription Drugs. New York: Harper Perennial, 1995.

Mills, Simon, and Stephen J. Finando. Alternatives in Healing. New York: New American Library, 1989.

National Institutes of Health. Restless Legs Syndrome: Detections and Management in Primary Care. Bethesda, MD: NIH, 2000.

Periodicals

O'Keeffe, Shaun T. "Restless Legs Syndrome: A Review." Archives of Internal Medicine 56 (Feb 12, 1996): 243-246.

Organizations

Restless Legs Syndrome Foundation. 1904 Banbury Road. Raleigh, NC 27608-4428. (919) 781-4428. http://www.rls.org.

[Article by: Judith Turner]

Wikipedia: Restless legs syndrome
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Restless legs syndrome Image = RLS-Schlafmuster.png
Classification and external resources
ICD-10 G25.8
ICD-9 333.94
OMIM 102300 608831
DiseasesDB 29476
eMedicine neuro/509
MeSH D012148

Restless legs syndrome (RLS), also known as Wittmaack-Ekbom's syndrome, and colloquially as "the jimmylegs" is a condition that is characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can also affect the arms or torso and even phantom limbs.[1] Moving the affected body part modulates the sensations, providing temporary relief.

RLS causes a sensation in the legs or arms that can most closely be compared to a burning, itching, or tickling sensation in the muscles. Some controversy surrounds the marketing of drug treatments for RLS. It is a 'spectrum' disease with some people experiencing only a minor annoyance and others experiencing major issues.

Contents

Signs and symptoms

The sensations—and the need to move—may return immediately after ceasing movement or at a later time. RLS may start at any age, including early childhood, and is a progressive disease for a certain portion of those afflicted, although the symptoms have disappeared permanently in some sufferers.[citation needed]

  • "An urge to move, usually due to uncomfortable sensations that occur primarily in the legs, but occasionally in the arms or elsewhere."[citation needed]
The sensations are unusual and unlike other common sensations, and those with RLS have a hard time describing them. People use words such as: uncomfortable, "antsy", electrical, creeping, painful, itching, pins and needles, pulling, creepy-crawly, ants inside the legs, numbness, and many others. While it may be impossible to describe the sensation to someone without RLS, other RLS sufferers can easily relate to the peculiar sensation. The sensation and the urge can occur in any body part; the most cited location is legs, followed by arms. Some people have little or no sensation, yet still have a strong urge to move.
  • "Motor restlessness, expressed as activity, that relieves the urge to move."[citation needed]
Movement will usually bring immediate relief; however, this relief will often be only temporary and partial. Walking is most common; however, doing stretches, yoga, biking, or other physical activity may relieve the symptoms. Continuous, fast up-and-down movements of the leg, is often done to keep the sensations at bay without having to walk. Sometimes a specific type of movement will help a person more than another.
Any type of inactivity involving sitting or lying down: reading a book, a plane ride, watching TV or a movie, or taking a nap can trigger the sensations and urge to move. This depends on several factors: the severity of the person’s RLS, the degree of restfulness, the duration of the inactivity, etc.
  • "Variability over the course of the day-night cycle, with symptoms worse in the evening and early in the night."[citation needed]
While some only experience RLS at bedtime and others experience it throughout the day and night, most sufferers experience the worst symptoms in the evening and the least in the morning.

NIH criteria

In 2003, a National Institutes of Health (NIH) consensus panel modified their criteria to include the following:

  1. an urge to move the limbs with or without sensations
  2. improvement with activity
  3. worsening at rest
  4. worsening in the evening or night.[2]

RLS is either primary or secondary.

  • Primary RLS is considered idiopathic, or with no known cause. Primary RLS usually begins before approximately 40 to 45 years of age, and can even occur as early as the first year of life.[citation needed] In primary RLS, the onset is often slow. The RLS may disappear for months, or even years. It is often progressive and gets worse as the person ages. RLS in children is often misdiagnosed as growing pains.
  • Secondary RLS often has a sudden onset and may be daily from the very beginning. It often occurs after the age of 40, however it can occur earlier. It is most associated with specific medical conditions or the use of certain drugs (see below).

Causes

Disease mechanism

Most research on the disease mechanism of restless legs syndrome has focused on the dopamine and iron system.[3][4] These hypotheses are based on the observation that levodopa and iron can be used to treat RLS, but also on findings from functional brain imaging (such as positron emission tomography and functional magnetic resonance imaging), autopsy series and animal experiments.[5] Differences in dopamine- and iron-related markers have also been demonstrated in the cerebrospinal fluid of individuals with RLS.[6] A connection between these two systems is demonstrated by the finding of low iron levels in the substantia nigra of RLS patients, although other areas may also be involved.[7]

Underlying disorders

The most commonly associated medical condition is iron deficiency (specifically blood ferritin below 50 µg/L[8]), which accounts for just over 20% of all cases of RLS. Other conditions associated with RLS include varicose vein or venous reflux, folate deficiency, magnesium deficiency, sleep apnea, uremia, diabetes, thyroid disease, peripheral neuropathy, Parkinson's disease and certain auto-immune disorders such as Sjögren's syndrome, celiac disease, and rheumatoid arthritis. RLS can also worsen in pregnancy.[9] In a recent study, RLS was detected in 36% of patients attending a phlebology (vein disease) clinic, compared to 18% in a control group.[10]

Certain medications may worsen RLS in those who already have it, or cause it secondarily. These include: some antiemetics (the dopaminergic ones), certain antihistamines (often in over-the-counter cold medications), many antidepressants (both older TCAs and newer SSRIs), antipsychotics, and certain anticonvulsants. Treatment of underlying conditions, or cessation of use of the offending drug, often eliminates the RLS. Restless legs syndrome can occur as a result of the benzodiazepine withdrawal syndrome when discontinuing benzodiazepine tranquillisers or sleeping pills. A sedative hypnotic with a short half life may also induce restless legs syndrome when the dose wears off as part of a rebound effect.[11]

Hypoglycemia has also been found to worsen RLS symptoms.[12] Opioid detoxification has also recently been associated with provocation of RLS-like symptoms during withdrawal. [13] For those affected, a reduction or elimination in the consumption of simple and refined carbohydrates or starches (for example, sugar, white flour, white rice and white potatoes) or some hard fats, such as those found in beef or biscuits, is recommended. Some doctors believe it is caused by irregular electrical impulses from the brain.[citation needed]

Both primary and secondary RLS can be worsened by surgery of any kind, however back surgery or injury can be associated with causing RLS.[14]

Some experts believe RLS and periodic limb movement disorder are strongly associated with ADHD in some children. Dopamine appears to factor into both conditions. In addition, many types of medication for the treatment of both conditions affect dopamine levels in the brain.[15]

The cause vs. effect of certain conditions and behaviors that are observed in some patients (ex. carrying excess weight, lack of exercise, suffering from depression or other mental illnesses) does not appear to be well established. The loss of sleep due to RLS could be the cause of the conditions, or the medication used to treat a condition could be the cause of an individual's RLS.[16][17]

Genetics

More than 60% of cases of RLS are familial[18] and are inherited in an autosomal dominant fashion with variable penetrance.

No one knows the exact cause of RLS at present. Research and brain autopsies have implicated both dopaminergic system and iron insufficiency in the substantia nigra (study published in Neurology, 2003).[19] Iron is an essential cofactor for the formation of L-dopa, the precursor of dopamine.

Six genetic loci found by linkage are currently known and are listed below. Other than the first one in this list, the remainder of the linkage loci were discovered using an autosomal dominant model of inheritance.

  • The second RLS locus maps to chromosome 14q and was discovered in one Italian family.[23] Evidence for this locus was found in one French Canadian family.[24] Also, an association study in a large sample 159 trios of European descent showed some evidence for this locus.[25]
  • The third locus maps to chromosome 9p and was discovered in two unrelated American families.[26] Evidence for this locus was also found by the TDT in a large Bavarian family,[27] as well as in a German family, in which significant linkage to this locus was found.[28]
  • The next locus maps to chromosome 20p and was discovered in a large French Canadian family with RLS.[29]
  • The fifth locus maps to chromosome 2p and was found in three related families from population isolate in Bolzano-Bozen.[30]
  • The sixth locus is located on chromosome 16p12.1 and was discovered by Levchenko et. al in 2008[31].

Three genes, MEIS1, BTBD9 and MAP2K5, were found to be associated to RLS.[32] Their role in RLS pathogenesis is still unclear. More recently, a fourth gene, PTPRD was found to be associated to RLS [33]

There is also some evidence that periodic limb movements in sleep (PLMS) are associated with BTBD9 on chromosome 6p21.2.[34]

Diagnosis

The diagnosis of RLS relies essentially on a good medical history and physical examination. Sleep registration in a laboratory (polysomnography) is not necessary for the diagnosis. Peripheral neuropathy, radiculopathy and leg cramps should be considered in the differential diagnosis; in these conditions, pain is often more pronounced than the urge to move. Akathisia, a side effect of several antipsychotics or antidepressants, is a more constant form of leg restlessness without discomfort. Doppler ultrasound evaluation of the vascular system is essential in all cases to rule out venous disorders which is common etiology of RLS. A rare syndrome of painful legs and moving toes has been described, with no known cause.[35]

Prevention

Other than preventing the underlying causes, no method of preventing restless legs has been established or studied.[citation needed]

Treatment

An algorithm for treating primary RLS (i.e., RLS that is not the result of another medical condition) was created by leading researchers at the Mayo Clinic and is endorsed by the Restless Legs Syndrome Foundation. This document provides guidance to both the treating physician and the patient, and includes both nonpharmacological and pharmacological treatments.[36] Treatment of primary RLS should not be considered until possible precipitating medical conditions are ruled out, especially venous disorders. Drug therapy in RLS is not curative and is known to have side effects such as nausea, dizziness, hallucinations, orthostatic hypotension, and sudden sleep attacks during the daytime. In addition, it can be expensive (about $100–150 per month for life), and thus it needs to be considered with caution.[citation needed]

Secondary RLS has the potential for cure if the precipitating medical conditions, anaemia, venous disorder, etc., are managed effectively. In many instances the alleged secondary conditions might be the only conditions causing the RLS; these include iron deficiency, varicose veins, and thyroid problems. Karl Ekbom in his original thesis on RLS in 1945 had suspected venous disease in about 12.5% of the cases he studied. But due to the unavailability of Doppler ultrasound imaging technology (the diagnostic tool that detects the abnormal blood flow in the veins, "Venous Reflux", the pathological basis for varicose veins) at that time, Ekbom may have underestimated the role of venous disease. In uncontrolled prospective series, improvement of RLS was achieved in a high percentage of patients who had presented with a combination of RLS and venous disease and had sclerotherapy or other treatment for the correction of venous insufficiency.[37][38]

Stretching & Shaking Legs

Stretching the muscles in the legs can bring instant relief.[39][40]

Iron supplements

According to some guidelines[citation needed], all people with RLS should have their ferritin levels tested; ferritin levels should be at least 50 µg for those with RLS. Oral iron supplements, taken under a doctor's care, can increase ferritin levels. For some people, increasing ferritin will eliminate or reduce RLS symptoms. A ferritin level of 50 µg is not sufficient for some sufferers and increasing the level to 80 µg may greatly reduce symptoms. However, at least 40% of people will not notice any improvement. Treatment with IV iron is being tested at the US Mayo Clinic and Johns Hopkins Hospital. It is dangerous to take iron supplements without first having ferritin levels tested, as many people with RLS do not have low ferritin and taking iron when it is not called for can cause iron overload disorder, potentially a very dangerous condition.[41]

Pharmaceuticals

For those whose RLS disrupts or prevents sleep or regular daily activities, medication may be required. Many doctors currently use, and the Mayo Clinic algorithm includes,[36] medication from four categories:

  1. Dopamine agonists such as ropinirole, pramipexole, carbidopa/levodopa or pergolide. Ropinirole (Requip) was first approved In 2005 by the US Food and Drug Administration (FDA) to treat moderate to severe Restless Legs Syndrome. The drug was first approved for Parkinson's disease in 1997. Pramipexole (Mirapex, Sifrol, Mirapexen in the EU) received a positive recommendation by the EU Scientific Committee in February 2006. The FDA approved Mirapex for sale in the US in 2006. Rotigotine (Neupro), which is delivered by a transdermal patch was approved by the FDA in May 2007 for early stage Parkinson's disease; it is not yet approved for RLS in the US. Rotigotine (Neupro), was approved for sale in the EU in 2007 for not only advanced stage Parkinson's disease but also for RLS. There are some issues with the use of dopamine agonists. Dopamine agonists may cause augmentation. This is a medical condition where the drug itself causes symptoms to increase in severity and/or occur earlier in the day. Dopamine agonists may also cause rebound, when symptoms increase as the drug wears off. Also, a recent study indicated that dopamine agonists used in restless leg patients can lead to an increase in compulsive gambling.[42]
  2. Opioids such as propoxyphene, oxycodone, or methadone, and mainly tramadol
  3. Benzodiazepines, such as diazepam, which often in addition to symptom relief assist in staying asleep and reducing awakenings from the movements
  4. Anticonvulsants, such as carbamazepine, help people who experience the RLS sensations as painful. [43]

Recently, several major pharmaceutical companies are reported to be marketing drugs without an explicit approval for RLS, which are "off-label" applications for drugs approved for other diseases. The Restless Legs Syndrome Foundation[44] received 44% of its $1.4 million in funding from these pharmaceutical groups[45]

Ropinirole vs. Pramipexole

A meta-analysis published November 2007 combined previous 6-12 week long placebo-controlled studies done for ropinirole and pramipexole to indirectly compare adverse reactions and efficacy. It found that while both drugs had the same efficacy, pramipexole had significantly lower incidences of nausea, vomiting and dizziness. This led the authors to conclude "differences in efficacy and tolerability favouring pramipexole over ropinirole can be observed."[46]

The non drug musculoskeletal approach

The non-drug musculoskeletal approach has been developed by a small group of doctors working at the London College of Osteopathic Medicine, London, UK and appears to produce relief of symptoms in 80–90% of patients. A small pilot study carried out at the London College of Osteopathic Medicine, using a specific form of manipulation, showed successful relief of symptoms in more that 80% of sufferers [47]. This followed the empirical observation that a large proportion of RLS sufferers have a "somatic dysfunction" at the lowermost level of the lumbar spine, and that a specific type of gentle manipulation could relieve their symptoms. One study has shown that RLS patients have increased rather than the normal decreased spinal cord excitability during sleep[48] and this fits with the osteopathic concept of spinal facilitation postulated by Korr. Specific types of manipulation appear to reduce this excessive sensory input and relieve symptoms. This non drug treatment approach is free of the side effects associated with many of the drug treatments outlined above.

Prognosis

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.

Epidemiology

Claims about the prevalence of restless legs syndrome can be confusing because its severity and frequency varies enormously between individual sufferers. RLS affects an estimated 7% to 10% of the general population in North America and Europe.[49][50][51] minority of sufferers (around 2.7% of the population) experience daily or severe symptoms.[50] RLS is twice as common in women as in men,[52] and whites are more prone to RLS than African Americans.[49] RLS occurs in 3% of individuals from the Mediterranean or Middle Eastern region, and in 1-5% of those from the Far East, indicating that different genetic or environmental factors, including diet, may play a role in the prevalence of this syndrome.[49][53] With age, RLS becomes more common, and RLS diagnosed at an older age runs a more severe course.[54]

RLS is even more common in individuals with iron deficiency, pregnancy and end-stage renal disease.[55][56] Neurologic conditions linked to RLS include Parkinson disease, spinal cerebellar atrophy, spinal stenosis, lumbosacral radiculopathy and Charcot-Marie-Tooth disease type 2.[49] Approximately 80–90% of people with RLS also have periodic limb movement disorder (PLMD), which causes slow "jerks" or flexions of the affected body part. These occur during sleep (PLMS = periodic limb movement while sleeping) or while awake (PLMW—periodic limb movement while waking).

The National Sleep Foundation's 1998 Sleep in America poll showed that up to 25 percent of pregnant women developed RLS during the third trimester.[57]

History

Earlier studies were done by Thomas Willis (1622–1675) and by Theodor Wittmaack.[58] Another early description of the disease and its symptoms were made by George Miller Beard (1839-1883).[58] In a 1945 publication titled 'Restless Legs', Swedish neurologist Karl-Axel Ekbom (1907-1977)[58] described the disease and presented eight cases used for his studies.[59]

Controversy

As with many diseases with diffuse symptoms, there is controversy among physicians as to whether RLS is a distinct syndrome. The U.S. National Institute of Neurological Disorders and Stroke publishes an information sheet[60] characterizing the syndrome but acknowledging it as a difficult diagnosis. Some physicians doubt that RLS actually exists as a legitimate clinical entity, but believe it to be a kind of "catch-all" category, perhaps related to a general heightened sympathetic nervous system response that could be caused by any number of physical or emotional factors[citation needed]. Other physicians consider it a real entity that has specific diagnostic criteria.[61]

However, RLS and delusional parasitosis are entirely different conditions that share part of the Wittmaack-Ekbom syndrome eponym, as both syndromes were described by the same person, Karl-Axel Ekbom.[58]

Many doctors express the view that the incidence of restless leg syndrome is exaggerated by manufacturers of drugs used to treat it.[62] Others believe it is an underrecognized and undertreated disorder.[49] Some of the controversy results from the fact that certain pharmaceutical companies used medical representatives (i.e., salespeople) to perform investigations into the treatment of RLS, even though those companies had no licensed treatments for the condition. Further, GlaxoSmithKline ran advertisements that, whilst not promoting off-license use of their drug (ropinirole) for treatment of RLS, did link to the Eckbom Support Group website. That website contained statements advocating the use of ropinirole to treat RLS. The ABPI ruled against GSK in this case.[63]

See also

References

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External links

v • d • e
Symptoms and signs: nervous and musculoskeletal systems (R25-R29, 781.0, 781.2-9)
Primarily nervous system
Primarily CNS
Lack of coordination
Other
Primarily PNS
Primarily muscular
Spasm (Trismus) · Fasciculation · Fibrillation · Myokymia · Cramp  · Restless legs syndrome
Other
Primarily skeletal
central nervous system navs: anat/physio/dev, noncongen/congen/neoplasia, symptoms+signs/eponymous, proc
peripheral nervous system navs: anat/histo/physio/dev, noncongen PNS somatic/autonomic/congen/neoplasia, symptoms+signs/eponymous, proc
muscle, DF+DRCT navs: anat/hist/physio, acquired myopathy/congenital myopathy/neoplasia, symptoms+signs/eponymous, proc
bone and cartilage navs: anat/physio/dev, noncongen/congen/neoplasia, symptoms+signs/eponymous signs, proc


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