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Department of Neurology

Houston, Texas

BCM neurologists see patients through the Baylor Clinic and some of the world's leading specialty clinics.
Department of Neurology
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Restless Legs Syndrome (RLS)

What is Restless Legs Syndrome (RLS)?

With the emergence of new, approved, treatments and increased public awareness, RLS is now recognized to be one of the most common movement disorders.  The diagnosis of RLS is entirely based on the symptoms that the patient reports. In 2003 a National Institute of Health (NIH) committee defined RLS as: 1. a desire to move the limbs, often associated with unpleasant sensations, 2. worsening of symptoms at physical and mental rest, 3. complete or partial relief with movement, and 4. worsening of symptoms in the evening or night. Some patients, however, may lose the diurnal pattern so that their RLS may not necessarily worsen at night.

The sensations that people feel are always unpleasant but not necessarily painful. The most common descriptions used include such words as “need to move”, “crawling”, “tingling”, “restless”, “cramping”, “creeping”, “pulling”, “painful”, “electric”, “tension”, “discomfort”, and “itching”. These sensations are usually deep in the limbs and can be improved by rubbing, hot/cold water, and by any movement. Patients often get up to walk around in an attempt to relieve the irresistible restlessness. Despite the name, RLS, these sensations may also be felt in the arms, although the legs are almost always more severely affected; the face and torso are rarely ever involved.

Since the sensations are worse at night, patients often have great difficulty in falling asleep. This sleep deprivation can lead to a variety of other problems including memory problems, depression, and even contribute to other medical problems such as hypertension.

Another feature that many patients with RLS have is called periodic limb movements of  sleep (PLMS). These are kick-like movements of the legs while patients are asleep. They can also occur when patients are drowsy but not yet asleep. This is often more of a problem for the bed partner, who may get kicked, than the patient, who if often unaware of these sleep-related movements.  

How common is RLS?

Several surveys have now shown that RLS affects between 5 and 15% of all people; women are more affected than men. In one study the prevalence among people in over the age of 50 was found to be 10.6% (14.2% in women, 6.6% in men). The chance of having RLS increases with age. RLS patients often do not see a physician until mid to later life but many actually report subtle symptoms dating from much earlier in their life. These symptoms typically worsen over time. The onset of mild symptoms during childhood or even infancy is not rare. Children, however, often do not report all the classical symptoms, and may just have irritability and difficulty concentrating. Some physicians feel that attention deficit hyperactivity disorder (ADHD) may actually be a form of RLS in certain cases, but this  relationship has not yet been clarified. RLS appears in all ethnic backgrounds and nationalities, although people from European descent (Caucasian) seem most like to have RLS.

What causes RLS?

The exact cause(s) of RLS are not known. The diagnosis of RLS is divided into a primary type and a secondary or symptomatic type. Patients with “primary” RLS have no other medical condition that causes their symptoms. In many cases of primary RLS there is a family history of similar symptoms in blood relatives. Therefore, this RLS is usually “genetic”. Often patients do not know that other family members suffer from the same condition because the relatives usually do not share the information about their RLS symptoms with their relatives or even their physicians and, hence, have never been diagnosed with RLS. It is very important to identify other family members that may have RLS because an identification of large families with RLS may help researchers find gene or genes that cause RLS. Once this is accomplished, it will greatly improve our understanding of the condition and may lead to DNA diagnostic tests. Such tests could then be used to confirm the diagnosis and to identify individuals at risk for developing the condition. Most researchers feel that RLS is inherited in an autosomal dominant pattern, which means that if someone has primary (genetic) RLS, then each of their children has a 50% chance of inheriting the gene and possibly developing the symptoms. Current research has identified four chromosomes (6, 9, 12, and 14) involved in RLS and more RLS-related genetic abnormalities are expected to be identified in the near future.  Based on some animal models developed by scientists at Baylor College of Medicine, the lower part of the brain (brainstem) has been implicated in the pathophysiology of RLS.

“Secondary” RLS means that another medical condition is the cause, or at least is associated with RLS symptoms. Several common conditions including neuropathy, kidney failure, iron deficiency, essential tremor, pregnancy, and certain drugs can cause RLS symptoms. “Neuropathy” means any damage to the nerves in the legs. There are many specific causes of “neuropathy”, some of which are treatable, but most of which are not. Kidney or renal failure (uremia) is usually diagnosed easily with blood tests. Up to 1/3 of all patients with kidney failure have RLS. Iron deficiency is usually confirmed measured by a blood test for serum iron and “ferritin” as well as other blood tests. Iron-deficiency anemia may not be present. Up to 1/3 of all women experience RLS during the last trimester of pregnancy. Symptoms, however, improve shortly after delivery. Several other conditions may also be associated with RLS.

Are there any tests for RLS?

There are tests that can identify some of the diseases that can cause “secondary” RLS. Iron deficiency should be excluded and tests for peripheral neuropathy, such as an electrical test called “nerve conduction velocity” (NCV) and “electromyogram” (EMG) may be warranted. There are, however, no diagnostic tests available for primary RLS. Patients occasionally have sleep studies (poly-somnograms) to document the leg kicking (PLMS).

What are the treatments for RLS?

No two patients respond identically to treatments for RLS. All treatments are felt to provide only symptom relief, rather than permanently cure RLS. Therefore, treatment should only be started when the benefits are felt to justify any potential side effects and costs. RLS is a chronic condition and, therefore, treatment decisions should take into account potential long-term issues and be individualized to the particular needs of the patient. Both dosing and medication changes are often required to maximize benefit and minimize the risk of tolerance and side effects over time.

Physical measures: It is clear that intense physical and even mental activity can forestall RLS symptoms. The problem is of course that symptoms are worst when people are trying to fall asleep, which is not a convenient time to exercise. There are certain situations, such as a plane flight, where intense concentration (i.e., a challenging video game) may improve symptoms.

No natural or over the counter (OTC) medications consistently improve RLS. OTC sleeping medicines such as Benadryl and melatonin may actually worsen symptoms. Some patients report that calcium and magnesium help them, but when these were examined scientifically they did not show any benefit. OTC iron supplements may help some people, however iron pills only mildly increase iron in the body. Less than 1% of the pill is actually absorbed from the stomach. Because of potential side effects patients should always check with their physicians before taking any OTC medications.

By far, the most consistently effective treatments for RLS are prescription medications. No medication has been specifically developed for RLS, but fortunately medications developed for other condition often help RLS symptoms.

Dopaminergic medications, which replace or imitate a brain chemical called dopamine, were developed to treat Parkinson’s disease (PD). It should be re-emphasized that RLS does not lead to PD, or any other neurological conditions, despite the fact that the same medications improve both PD and RLS. The first anti-PD drug found to help RLS was carbidopa/levodopa (Sinemet). While most RLS patients initially improve with levodopa, this improvement usually lessens over time. A series of other dopamine drugs called agonists (dopamine mimickers) have since been shown to markedly improve RLS symptoms, often more than Sinemet. These include pramipexole (Mirapex), ropinirole (Requip), and rotigotine (Neupro); only the first two dopamine agonists are currently approved for use by the Food and Drug Administration. No one drug is consistently better than the others. Side effects of these dopamine drugs are generally mild but may include nausea, lightheadedness associated with low blood pressure, sleepiness (often welcomed), and nasal congestion. Both tolerance, symptom augmentation, and late night or early morning rebound symptoms may develop, necessitating temporary drug withdraw (“drug holiday”).

Narcotic or opioid medication used to treat pain can also help RLS symptoms. These include mostly older medications: morphine, methadone, codeine, oxycodone, hydrocodone, and propoxyphene. Again no single medication is consistently best, however in any single patient, one medication may be superior to the others. Possible side effects of these medications include constipation, nausea, and sedation. The biggest concern about using these medications is that their use may cause psychological addiction and physical dependence. Nevertheless, in cases with very severe RLS, these drugs may be the only option.

Benzodiazepines, which are often used as regular sleeping pills or anxiety medications, are often used for RLS. Common benzodiazepines include diazepam (Valium), clonazepam (Klonopin), alprazolam (Xanax), and lorazepam (Ativan). Our experience is that these medications can help patients fall asleep, but do not help the leg sensations much, except in milder cases. There is also not much scientific evidence that they are very beneficial for RLS. Several medications developed for treatment of epilepsy may also help RLS, including carbamazepine (Tegretol), gabapentin (Neurontin), topiramate (Topamax), and pregabalin (Lyrica).

Sometimes, combinations of these different types of drugs are needed to control severe symptoms, and often medicines may work for a period of time before needing to be replaced by other medications. The dose of medication and the time at which they are given depend on the duration and intensity of symptoms. In all cases patients should take the lowest dose that controls their individual symptoms.

Selected References

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  • Chokroverty S, Jankovic J. Restless legs syndrome. A disease in search of identity. Neurology 1999;52:907-10.
  • Earley CJ. Restless legs syndrome. N Engl J Med 2003;348:22103-9.
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  • Kenney C, Jankovic J. Rotigotine transdermal patch in the treatment of Parkinson's disease and restless legs syndrome. Expert Opin Pharmacother 2007;8:1329-1335.
  • Mata IF, Bodkin CL, Adler CH, Uitti RJ, Wszolek ZK et al. Genetics of restless legs syndrome. Parkinsonism Relat Disord 2006;12;1-7
  • McCormack PL, Siddiqui MA. Pramipexole: in restless legs syndrome. CNS Drugs 2007;21:429-37.
  • Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, Lesperance P. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: A study of 133 patients diagnosed with new standard criteria. Mov Disord 1997;12:61-5.
  • Oertel WH, Trenkwalder C, Zucconi M et al. State of the art in restless legs syndrome therapy: Practice recommendations for treating restless legs syndrome. Mov Disord 2007 Epub ahead of print
  • Ondo WG, Jankovic J. Restless legs syndrome: Clinical Etiologic Correlates. Neurology 1996;47:1435-1441.
  • Ondo WG, Tan EK, Mansoor J. Rheumatologic serologies in restless legs syndrome. Mov Disord 2000;15: 321-323.
  • Ondo WG, Vuong KD, Wang Q. Restless legs syndrome in monozygotic twins: Phenotype and serologic correlations. Neurology 2000;55:1404-1406.
  • Ondo WG, Romanyshyn J, Vuong K, Lai D. The Long-term treatment of restless legs syndrome with dopamine agonists. Arch Neurol 2004;1393-1397.
  • Ondo WG. Methadone for refractory restless legs syndrome. Mov Disord 2005;20:345-8.
  • Ondo WG, Zhao HR, Le WD. Animal models of restless legs syndrome. Sleep Med 2007;8:344-8.
  • Shen C, Ondo WG, Rao S, Li L, Wang Q. Genome-wide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p. Am J Hum Gen 2004;74:876-885.
  • Stefansson H, Rye DB, Hicks A, et al. A genetic risk factor for periodic limb movements in sleep. N Engl J Med 2007;357:639-47.
  • Winkelman JW, Allen RP, Tenzer P, Hening W. Restless legs syndrome: nonpharmacologic and pharmacologic treatments. Geriatrics 2007;62:13-6.

Appendix

Restless Legs Syndrome Foundation
819 Second Street SW
Rochester, MN 55902-2985
Tel: 507-287-6465
Fax: 507-287-6312
Email: rlsfoundation@rls.org
www.rls.org

For additional information visit http://www.bcm.edu/neurology/pdcmdc/