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Medical Encyclopedia:

Restless Legs Syndrome

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


 
 
Sci-Tech Dictionary: restless legs syndrome
(′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

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

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

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
Restless legs syndrome
Classification & external resources
RLS-Schlafmuster.png
Sleep pattern of a Restless Legs Syndrome patient (red) vs. a healthy sleep pattern (blue).
ICD-10 G25.8
ICD-9 333.94
OMIM 102300 608831
DiseasesDB 29476
eMedicine neuro/509 
MeSH D012148

Restless legs syndrome (RLS, or Wittmaack-Ekbom's syndrome) is a condition that is characterised by an irresistible urge to move one's legs. It is poorly understood [citation needed], often misdiagnosed, and believed to be a neurological disorder.

It is sometimes mistakenly called "Ekbom's syndrome," but that is an entirely different condition that shares part of the Wittmaack-Ekbom syndrome eponym: delusional parasitosis, as both syndromes were described by the same person, Karl-Axel Ekbom. [1]

Many doctors express the view that the incidence of restless leg syndrome is exaggerated by manufacturers of drugs used to treat it.[2] Other physicians consider it a real entity that has specific diagnostic criteria. [3]

Many people tap their feet or shake their legs resulting from a nervous tic, consumption of stimulants, drug side-effects or other factors; this is usually innocuous, unnoticed, and does not interfere with daily life, quite distinct from Restless Leg Syndrome.

Explanation

Restless Leg Syndrome (RLS) (which is also sometimes referred to as Jimmy Legs) may be described as uncontrollable urges to move the limbs to stop uncomfortable or odd sensations in the body, most commonly in the legs, but can also be in the arms and torso. Moving the affected body part modulates the sensations, providing temporary relief.

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.

As with many diseases with diffuse symptoms, there is controversy among physicians, if RLS is a distinct syndrome. The US National Institute of Neurological Diseases and Stroke publishes an information sheet [4] characterizing the syndrome but acknowledging it is 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 (SNS) response that could be caused by any number of physical or emotional factors [citation needed]. Other clinicians associate it with lumbosacral spinal subluxations and life stress.[citation needed] Another possible explanation of RLS is acidosis, though this claim needs to be explored further. RLS as a result of acidosis/insufficient oxygen being circulated to the legs (which reduces acid build up) would explain why symptoms worsen when the legs are at rest, and why moving them (increasing circulation) offers some relief. The fact that iron offers relief for many can be explained by its vital role in hemoglobin, which is responsible for oxygen dispersion to the tissues. The legs would be more prone to the restless condition since they are furthest from the heart and lungs. Additionally, one may see below that many of the "lifestyle changes and other non-medicinal approaches" are related in some way or form to circulation (e.g. heat, stretching, movement), acid build up (e.g. too much exercise, ketosis from high-fat diets), or the amount of oxygen being dispersed in the blood (e.g. deep breathing, iron levels). It should be noted that this potential causal relationship between RLS and acidosis is purely speculative the time being, as far as the contributing editor is aware. If this causal relationship holds true, then finding the cause of the acidosis would most likely lead to the best treatment.

Some experts believe RLS and periodic limb movement disorder are strongly associated with ADHD in some children. Both conditions are hereditary and dopamine is believed to be involved. Many types of medication for both conditions are affecting the dopamine levels in the brain [1]

Symptoms

  • "An urge to move, usually due to uncomfortable sensations that occur primarily in the legs."

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, and many others. 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."

Movement will usually bring immediate relief, however, often only temporary and partial. Walking is most common; however, doing stretches, yoga, biking, or other physical activity may relieve the symptoms. Constant and fast up-and-down movement of the leg, coined "sewing machine legs" by at least one RLS sufferer, 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.

  • "Worsening of symptoms by relaxation."

Any type of inactivity involving sitting or lying – reading a book, a plane ride, watching TV or a movie, 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."

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) worsening at rest
  • (3) improvement with activity
  • (4) worsening in the evening or night.[5]

Incidence/Prevalence

Restless Leg Syndrome affects an estimated 2.7% of the general population in the U.S.A..[6]

Often sufferers think they are the only ones to be afflicted by this peculiar condition and are relieved when they find out that many others also suffer from it. The severity and frequency of the disorder vary tremendously. Many people only experience symptoms when they try to sleep, while others experience symptoms during the day. It is common to have symptoms on long car rides or during any long period of inactivity (like watching television or a movie, attending a musical or theatrical performance, etc.) Approximately 80-90% of people with RLS also have PLMD, Periodic Limb Movement Disorder, 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).

About 10 percent of adults in North America and Europe may experience RLS symptoms, according to the National Sleep Foundation, which reports that "lower prevalence has been found in India, Japan and Singapore," indicating that ethnic factors, including diet, may play a role in the prevalence of this syndrome.[7]

History

In a 1945 publication titled 'Restless Legs', Karl-Axel Ekbom described the disease and presented eight cases used for his studies.[8]

Earlier studies were done by Thomas Willis (1622-1675) and by Theodor Wittmaack.[1] Another early description of the disease and its symptoms were made by George Miller Beard (1839-1883).[1]

Types

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. 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. The most commonly associated medical condition is iron deficiency, which accounts for just over 20% of all cases of RLS. The conditions include: pregnancy, varicose vein or venous reflux, folate deficiency, sleep apnea, uremia, diabetes, thyroid problems, peripheral neuropathy, Parkinson's disease and certain auto-immune disorders such as Sjögren's syndrome, Celiac Disease, and rheumatoid arthritis. Treatment of the underlying condition, or cessation of use of the offending drug, often eliminates the RLS.

Causes

See potential causal relationship between acidosis and RLS above in "Explanation." Dehydration may also be a cause of an urge to move one's legs, as some sufferers often find that drinking a glass of water may stop the urges for a short while. Certain medications may worsen RLS in those who already have it, or cause it secondarily. These include: anti-nausea drugs, certain antihistamines (often in over-the-counter cold medications), drugs used to treat depression (both older tricyclics and newer SSRIs), antipsychotic drugs, and certain medications used to control seizures.

Hypoglycemia has also been found to worsen RLS symptoms.[9] Opioid detoxification has also recently been associated with provocation of RLS-like symptoms during withdrawal. 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.

Both primary and secondary RLS can be worsened by surgery of any kind, however back surgery or injury can be associated with causing RLS.[10] RLS can worsen in pregnancy. [11]

Genetics

40% of cases of RLS are familial 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).[12] Iron is an essential cofactor for the formation of L-dopa, the precursor of dopamine. An Icelandic study in 2005 confirmed the presence of an RLS susceptibility gene also found previously in a smaller French-Canadian population.[13][14] Various studies suggest chromosome 12q may indicate susceptibility to RLS.[15]

Treatment

See potential causal relationship between acidosis and RLS above in "Explanation." An algorithm for treating Primary RLS ( RLS without any secondary medical condition including iron deficiency, varicose vein, thyroid, etc.) was created by leading RLS 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.[16] Treatment of primary RLS should not be considered unless all the secondary medical conditions are ruled out. Drug therapy in RLS is not curative and is known to have significant side effects and needs to be considered with caution. The secondary form of RLS has the potential for cure if the precipitating medical condition (iron deficiency, venous reflux/varicose vein, thyroid, etc.) is managed effectively.

Iron supplements

All people with RLS should have their ferritin levels tested; ferritin levels should be at least 50 mcg 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 mcg is not sufficient for some sufferers and increasing the level to 80 mcg 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.

New results from the first ever double-blind clinical study,[17] performed at Örebro University Hospital show that all 29 out of 60 patients that were treated with IV-infusion of up to a total of 1000 mg of iron (in the form of iron saccharose, Venofer), were markedly improved after 3 weeks. The effect lasted for 5-6 months. Those 31 receiving placebo had just a slight effect after 3 weeks that additionally disappeared rapidly.

The treatment was given even if iron deficiency was not shown according to ferritin levels. Worries of anaphylactic reactions did not come true. This is probably due to the form the IV iron was given. Anaphylaxis has been associated predominantly with dextran based infusions.

Lifestyle changes and other non-medicinal approaches

Treatment for RLS is based on how disruptive the symptoms are. All people should review their lifestyle and see what changes could be made to reduce or eliminate their RLS symptoms. These include: finding the right level of exercise (too much worsens it, too little may trigger it); eliminating caffeine, smoking, and alcohol; changing the diet to eliminate foods that trigger RLS (different for each person, but may include eliminating sugar, triglycerides, gluten, sugar substitutes (aspartame), following a low-fat diet, etc.); keeping good sleep hygiene; treating conditions that may cause secondary RLS; avoiding or stopping OTC or prescription drugs that trigger RLS; adding supplements such as potassium, magnesium, B-12, folate, vitamin E, and calcium. Some of these changes, such as diet (particularly aspartame) and adding supplements are based on anecdotal evidence from RLS sufferers as few studies have been done on these alternatives.

For those who experience RLS infrequently and do not need or want to try medication, in addition to lifestyle changes they can try:

  • some form of exercise for several minutes such as walking, stretching, meditation, yoga, etc. at bedtime
  • heat or cold, such as a hot or cold bath, a heating pad, a cold cloth, or a fan
  • soaking one's feet in hot water just prior to going to sleep
  • engrossing the mind in a game, the computer, or figuring something out
  • wearing compression stockings, tight pantyhose, or wrapping the legs in elastic bandages
  • placing a pillow between the knees or upper-legs while lying in bed
  • eating porridge oats or almonds daily for their magnesium content [citation needed]
  • hot green tea can relieve symptoms[citation needed]
  • deep breathing for one or two minutes
  • Massage and chiropractic spinal manipulation provide significant relief for some patients.[citation needed]

Medicinal approaches

For those whose RLS disrupts or prevents sleep or regular daily activities, medication is often required. Many Doctors currently use, and the Mayo Clinic Algorithm includes,[16] medication from four categories:

Agent Timeline Comments
ropinirole Approved In 2005 by the Food and Drug Administration 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) In February 2006, the EU Scientific Committee issued a positive recommendation for approving for the treatment of RLS in the EU. US FDA approved Mirapex in 2006. -
rotigotine Currently in process for US FDA and EU approval for RLS Delivered via a transdermal patch
pergolide In March 2007 was withdrawn from the U.S. market Withdrawn due to implication in valvular heart disease, that was shown in two independent studies.

There are some issues with the use of dopamine augmentation. 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.[18]

In a study of 10 patients, it was reported that partial relief with taking a supplemental magnesium salt[19] such as magnesium oxide or magnesium gluconate once or twice a day, and reducing the dose if diarrhea develops. Magnesium sulfate is the most active form; however, magnesium supplementation can cause complications for patients with renal problems.[20]

Controversies


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 Leg Foundation [21] received 44% of its $1.4 million in funding from these pharmaceutical groups[22]. This has called into question the neutrality of this group (significant conflict of interest issue) and the course of action which they recommend to RLS patients.

See also

References

  1. ^ a b c Wittmaack-Ekbom syndrome at Who Named It
  2. ^ Woloshin S, Schwartz L (2006). "Giving legs to restless legs: a case study of how the media helps make people sick". PLoS Med. 3 (4): e170. PMID 16597175. 
  3. ^ Montplaisir J; Boucher S; Nicolas A; Lesperance P; Gosselin A; Rompré P; Lavigne G (1998). "{{{title}}}". Movement disorders 13 (2): 324-9. PMID 9539348. 
  4. ^ Restless Legs Syndrome Fact Sheet
  5. ^ Allen R, Picchietti D, Hening W, Trenkwalder C, Walters A, Montplaisi J (2003). "Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health.". Sleep Med 4 (2): 101-19. PMID 14592341. 
  6. ^ Allen R, Walters A, Montplaisir J, Hening W, Myers A, Bell T, Ferini-Strambi L (2005). "Restless legs syndrome prevalence and impact: REST general population study". Arch. Intern. Med. 165 (11): 1286-92. PMID 15956009. 
  7. ^ Welcome - National Sleep Foundation. Retrieved on 2007-07-23.
  8. ^ Ekbom, K.-A. Restless legs: a clinical study. Acta Med. Scand. (Suppl.) 158: 1-123, 1945.
  9. ^ Kurlan R (1998). "Postprandial (reactive) hypoglycemia and restless leg syndrome: related neurologic disorders?". Mov. Disord. 13 (3): 619-20. DOI:10.1002/mds.870130349. PMID 9613772. 
  10. ^ Crotti FM, Carai A, Carai M, Sgaramella E, Sias W (2005). "Entrapment of crural branches of the common peroneal nerve". Acta Neurochir. Suppl. 92: 69-70. PMID 15830971. 
  11. ^ McParland P, Pearce JM (1988). "Restless leg syndrome in pregnancy". BMJ 297 (6662): 1543. PMID 3147073. 
  12. ^ Connor J, Boyer P, Menzies S, Dellinger B, Allen R, Ondo W, Earley C (2003). "Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome.". Neurology 61 (3): 304-9. PMID 12913188. 
  13. ^ Desautels A, Turecki G, Montplaisir J, Sequeira A, Verner A, Rouleau G (2001). "Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q.". Am J Hum Genet 69 (6): 1266-70. PMID 11704926. 
  14. ^ Levchenko A, Montplaisir J, Dubé M, Riviere J, St-Onge J, Turecki G, Xiong L, Thibodeau P, Desautels A, Verlaan D, Rouleau G (2004). "The 14q restless legs syndrome locus in the French Canadian population.". Ann Neurol 55 (6): 887-91. PMID 15174026. 
  15. ^ Christopher J. Earley, M.B., B.Ch., Ph.D., "Restless Legs Syndrome" New England J Medicine 2003; 348:2103 - 9.
  16. ^ a b Mayo Clinic Algorithm also available as .pdf
  17. ^ Järninfusioner minskar symtomen vid restless legs. Retrieved on 2007-07-23.
  18. ^ "Medical Therapy for Restless Legs Syndrome may Trigger Compulsive Gambling", Mayo Clinic in Rochester, February 08, 2007
  19. ^ Hornyak M, Voderholzer U, Hohagen F, Berger M, Riemann D (1998). "Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study". Sleep 21 (5): 501-5. PMID 9703590. 
  20. ^ Magnesium Supplements (Systemic) - MayoClinic.com. Retrieved on 2007-08-08.
  21. ^ * RLS Foundation
  22. ^ Marshall, Jessica, and Peter Aldhous. "Patient Groups Special." New Scientist, 10/26/06

External links