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<p><strong>Restless legs syndrome</strong> (RLS, <strong>Wittmaack-Ekbom's syndrome</strong>, or sometimes referred to as Nocturnal myoclonus) is a condition that is characterized by an irresistible urge to move one's legs. It is 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.</p>
<p>Many doctors express the view that the incidence of restless leg syndrome is exaggerated by manufacturers of drugs used to treat it.<sup class="reference" id="_ref-0">[1]</sup> Other physicians consider it a real entity that has specific diagnostic criteria. <sup class="reference" id="_ref-1">[2]</sup></p>
<p>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, which is very different. With a nervous tic, someone does not necessarily notice it, but in RLS it is very noticeable. With a nervous tic, someone may tap their leg or foot, but with RLS you feel an undescribable sensation in your legs that can most closely be compared to a burning, itching sensation in the muscles of the legs or arms.</p>
<p><br />
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<h2><span class="mw-headline">Signs and symptoms</span></h2>
<p>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.</p>
<p>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 the treatment of both conditions affect dopamine levels in the brain. [1]</p>
<ul>
<li>"An urge to move, usually due to uncomfortable sensations that occur primarily in the legs." </li>
</ul>
<p>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.</p>
<ul>
<li>"Motor restlessness, expressed as activity, that relieves the urge to move." </li>
</ul>
<p>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.</p>
<ul>
<li>"Worsening of symptoms by relaxation." </li>
</ul>
<p>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.</p>
<ul>
<li>"Variability over the course of the day-night cycle, with symptoms worse in the evening and early in the night." </li>
</ul>
<p>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.</p>
<p> </p>
<h3><span class="mw-headline">NIH criteria</span></h3>
<p>In 2003, a National Institutes of Health (NIH) consensus panel modified their criteria to include the following:</p>
<ul>
<li>(1) an urge to move the limbs with or without sensations </li>
<li>(2) worsening at rest </li>
<li>(3) improvement with activity </li>
<li>(4) worsening in the evening or night.<sup class="reference" id="_ref-2">[3]</sup> </li>
</ul>
<p>RLS is either primary or secondary.</p>
<ul>
<li>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. </li>
</ul>
<ul>
<li>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. </li>
</ul>
<p> </p>
<h2><span class="mw-headline">Causes</span></h2>
<p>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.</p>
<p>Hypoglycemia has also been found to worsen RLS symptoms.<sup class="reference" id="_ref-pmid9613772_0">[4]</sup> 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. Some doctors believe it is caused by irregular electrical impulses from the brain.</p>
<p>Both primary and secondary RLS can be worsened by surgery of any kind, however back surgery or injury can be associated with causing RLS.<sup class="reference" id="_ref-pmid15830971_0">[5]</sup> RLS can worsen in pregnancy. <sup class="reference" id="_ref-pmid3147073_0">[6]</sup></p>
<p> </p>
<h3><span class="mw-headline">Genetics</span></h3>
<p>40% of cases of RLS are familial and are inherited in an autosomal dominant fashion with variable penetrance.</p>
<p>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).<sup class="reference" id="_ref-3">[7]</sup> 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.<sup class="reference" id="_ref-4">[8]</sup><sup class="reference" id="_ref-5">[9]</sup> Various studies suggest chromosome 12q may indicate susceptibility to RLS.<sup class="reference" id="_ref-6">[10]</sup></p>
<p>There is also some evidence that periodic limb movements in sleep may be associated with the iron-regulating <em>BTBD9</em> at 6p21.2.<sup class="reference" id="_ref-pmid17634447_0">[11]</sup></p>
<p> </p>
<h2><span class="mw-headline">Diagnosis</span></h2>
<p><font size="2"></font></p>
<h2><span class="mw-headline">Prevention</span></h2>
<p><font size="2"></font></p>
<h2><span class="mw-headline">Treatment</span></h2>
<p>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.<sup class="reference" id="_ref-MayoAlgo_0">[12]</sup> 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.</p>
<p> </p>
<h3> <span class="mw-headline">Iron supplements</span></h3>
<p>According to some guidelines<sup class="noprint Template-Fact"><span title="This claim needs references to reliable sources since December 2007" style="WHITE-SPACE: nowrap">[<em>citation needed</em>]</span></sup>, 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.<sup class="reference" id="_ref-pmid17516455_0">[13]</sup></p>
<p> </p>
<h3><span class="mw-headline">Pharmaceuticals</span></h3>
<p>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,<sup class="reference" id="_ref-MayoAlgo_1">[12]</sup> medication from four categories:</p>
<ol>
<li>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. It was approved for sale in the EU in 2007. 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.<sup class="reference" id="_ref-7">[14]</sup> </li>
<li>Opioids such as propoxyphene, oxycodone, or methadone, etc. </li>
<li>Benzodiazepines, which often assist in staying asleep and reducing awakenings from the movements </li>
<li>Anticonvulsants, which often help people who experience the RLS sensations as painful, such as gabapentin </li>
</ol>
<p>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 <sup class="reference" id="_ref-8">[15]</sup> received 44% of its $1.4 million in funding from these pharmaceutical groups<sup class="reference" id="_ref-9">[16]</sup></p>
<p> </p>
<h2><span class="mw-headline">Prognosis</span></h2>
<p><font size="2"></font></p>
<h2><span class="mw-headline">Epidemiology</span></h2>
<p>Restless leg syndrome affects an estimated 2.7% of the general population in the U.S.A., but claims about the prevalence of RLS can be confusing because its severity varies enormously between individual sufferers; only a minority of sufferers experience daily or severe symptoms.<sup class="reference" id="_ref-allen2005_0">[17]</sup></p>
<p>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 experience 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).</p>
<p>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.<sup class="reference" id="_ref-10">[18]</sup></p>
<p> </p>
<h2><span class="mw-headline">History</span></h2>
<p>Earlier studies were done by Thomas Willis (1622-1675) and by Theodor Wittmaack.<sup class="reference" id="_ref-WhoNamedIt_0">[19]</sup> Another early description of the disease and its symptoms were made by George Miller Beard (1839-1883).<sup class="reference" id="_ref-WhoNamedIt_1">[19]</sup> In a 1945 publication titled 'Restless Legs', Karl-Axel Ekbom described the disease and presented eight cases used for his studies.<sup class="reference" id="_ref-11">[20]</sup></p>
<p>As with many diseases with diffuse symptoms, there is controversy among physicians as to whether RLS is a distinct syndrome. The US National Institute of Neurological Disorders and Stroke publishes an information sheet <sup class="reference" id="_ref-12">[21]</sup> 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 (SNS) response that could be caused by any number of physical or emotional factors<sup class="noprint Template-Fact"><span title="This claim needs references to reliable sources since August 2007" style="WHITE-SPACE: nowrap">[<em>citation needed</em>]</span></sup>. Other clinicians associate it with lumbosacral spinal subluxations and life stress.<sup class="noprint Template-Fact"><span title="This claim needs references to reliable sources since August 2007" style="WHITE-SPACE: nowrap">[<em>citation needed</em>]</span></sup></p>
<p>The UK support group for RLS calls itself the "Ekbom support group" and explains that RLS and "Ekbom's Syndrome" are two names for the same condition. 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. <sup class="reference" id="_ref-WhoNamedIt_2">[19]</sup></p>
<p> </p>
<h2><span class="mw-headline">See also</span></h2>
<ul>
<li>Actigraphy </li>
<li>Parasomnia </li>
<li>Disease mongering </li>
<li>Akathisia: A similar condition. </li>
</ul>
<p> </p>
<h2><span class="mw-headline">References</span></h2>
<div class="references-small" style="column-count: 2; -moz-column-count: 2; -webkit-column-count: 2">
<ol class="references">
<li id="_note-0"><strong>^</strong> <cite style="FONT-STYLE: normal">Woloshin S, Schwartz L (2006). "Giving legs to restless legs: a case study of how the media helps make people sick". <em>PLoS Med.</em> <strong>3</strong> (4): e170. PMID 16597175.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Giving+legs+to+restless+legs%3A+a+case+study+of+how+the+media+helps+make+people+sick&rft.jtitle=PLoS+Med.&rft.date=2006&rft.volume=3&rft.issue=4&rft.au=Woloshin+S%2C+Schwartz+L&rft.pages=e170&rft_id=info:pmid/16597175&rft_id=http%3A%2F%2Fdx.doi.org%2F10.1371%2Fjournal.pmed.0030170"> </span> </li>
<li id="_note-1"><strong>^</strong> <cite style="FONT-STYLE: normal">Montplaisir J; Boucher S; Nicolas A; Lesperance P; Gosselin A; Rompré P; Lavigne G (1998). "{{{title}}}". <em>Movement disorders</em> <strong>13</strong> (2): 324-9. PMID 9539348.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Movement+disorders&rft.date=1998&rft.volume=13&rft.issue=2&rft.au=Montplaisir+J%3B+Boucher+S%3B+Nicolas+A%3B+Lesperance+P%3B+Gosselin+A%3B+Rompr%C3%A9+P%3B+Lavigne+G&rft.pages=324-9&rft_id=info:pmid/9539348&rft_id=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fsites%2Fentrez%3Fdb%3DPubMed%26cmd%3Dretrieve%26dopt%3DAbstractPlus%26list_uids%3D9539348"> </span> </li>
<li id="_note-2"><strong>^</strong> <cite style="FONT-STYLE: normal">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.". <em>Sleep Med</em> <strong>4</strong> (2): 101-19. PMID 14592341.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Restless+legs+syndrome%3A+diagnostic+criteria%2C+special+considerations%2C+and+epidemiology.+A+report+from+the+restless+legs+syndrome+diagnosis+and+epidemiology+workshop+at+the+National+Institutes+of+Health.&rft.jtitle=Sleep+Med&rft.date=2003&rft.volume=4&rft.issue=2&rft.au=Allen+R%2C+Picchietti+D%2C+Hening+W%2C+Trenkwalder+C%2C+Walters+A%2C+Montplaisi+J&rft.pages=101-19"> </span> </li>
<li id="_note-pmid9613772"><strong>^</strong> <cite style="FONT-STYLE: normal">Kurlan R (1998). "Postprandial (reactive) hypoglycemia and restless leg syndrome: related neurologic disorders?". <em>Mov. Disord.</em> <strong>13</strong> (3): 619-20. doi:10.1002/mds.870130349. PMID 9613772.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Postprandial+%28reactive%29+hypoglycemia+and+restless+leg+syndrome%3A+related+neurologic+disorders%3F&rft.jtitle=Mov.+Disord.&rft.date=1998&rft.volume=13&rft.issue=3&rft.au=Kurlan+R&rft.pages=619-20&rft_id=info:pmid/9613772&rft_id=info:doi/10.1002%2Fmds.870130349"> </span> </li>
<li id="_note-pmid15830971"><strong>^</strong> <cite style="FONT-STYLE: normal">Crotti FM, Carai A, Carai M, Sgaramella E, Sias W (2005). "Entrapment of crural branches of the common peroneal nerve". <em>Acta Neurochir. Suppl.</em> <strong>92</strong>: 69-70. PMID 15830971.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Entrapment+of+crural+branches+of+the+common+peroneal+nerve&rft.jtitle=Acta+Neurochir.+Suppl.&rft.date=2005&rft.volume=92&rft.au=Crotti+FM%2C+Carai+A%2C+Carai+M%2C+Sgaramella+E%2C+Sias+W&rft.pages=69-70&rft_id=info:pmid/15830971"> </span> </li>
<li id="_note-pmid3147073"><strong>^</strong> <cite style="FONT-STYLE: normal">McParland P, Pearce JM (1988). "Restless leg syndrome in pregnancy". <em>BMJ</em> <strong>297</strong> (6662): 1543. PMID 3147073.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Restless+leg+syndrome+in+pregnancy&rft.jtitle=BMJ&rft.date=1988&rft.volume=297&rft.issue=6662&rft.au=McParland+P%2C+Pearce+JM&rft.pages=1543&rft_id=info:pmid/3147073"> </span> </li>
<li id="_note-3"><strong>^</strong> <cite style="FONT-STYLE: normal">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.". <em>Neurology</em> <strong>61</strong> (3): 304-9. PMID 12913188.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Neuropathological+examination+suggests+impaired+brain+iron+acquisition+in+restless+legs+syndrome.&rft.jtitle=Neurology&rft.date=2003&rft.volume=61&rft.issue=3&rft.au=Connor+J%2C+Boyer+P%2C+Menzies+S%2C+Dellinger+B%2C+Allen+R%2C+Ondo+W%2C+Earley+C&rft.pages=304-9"> </span> </li>
<li id="_note-4"><strong>^</strong> <cite style="FONT-STYLE: normal">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.". <em>Am J Hum Genet</em> <strong>69</strong> (6): 1266-70. PMID 11704926.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identification+of+a+major+susceptibility+locus+for+restless+legs+syndrome+on+chromosome+12q.&rft.jtitle=Am+J+Hum+Genet&rft.date=2001&rft.volume=69&rft.issue=6&rft.au=Desautels+A%2C+Turecki+G%2C+Montplaisir+J%2C+Sequeira+A%2C+Verner+A%2C+Rouleau+G&rft.pages=1266-70"> </span> </li>
<li id="_note-5"><strong>^</strong> <cite style="FONT-STYLE: normal">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.". <em>Ann Neurol</em> <strong>55</strong> (6): 887-91. PMID 15174026.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+14q+restless+legs+syndrome+locus+in+the+French+Canadian+population.&rft.jtitle=Ann+Neurol&rft.date=2004&rft.volume=55&rft.issue=6&rft.au=Levchenko+A%2C+Montplaisir+J%2C+Dub%C3%A9+M%2C+Riviere+J%2C+St-Onge+J%2C+Turecki+G%2C+Xiong+L%2C+Thibodeau+P%2C+Desautels+A%2C+Verlaan+D%2C+Rouleau+G&rft.pages=887-91"> </span> </li>
<li id="_note-6"><strong>^</strong> Christopher J. Earley, M.B., B.Ch., Ph.D., "Restless Legs Syndrome" <em>New England J Medicine</em> 2003; 348:2103 - 9. </li>
<li id="_note-pmid17634447"><strong>^</strong> <cite style="FONT-STYLE: normal">Stefansson H, Rye DB, Hicks A, <em>et al</em> (2007). "A genetic risk factor for periodic limb movements in sleep". <em>N. Engl. J. Med.</em> <strong>357</strong> (7): 639–47. doi:10.1056/NEJMoa072743. PMID 17634447.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+genetic+risk+factor+for+periodic+limb+movements+in+sleep&rft.jtitle=N.+Engl.+J.+Med.&rft.date=2007&rft.volume=357&rft.issue=7&rft.au=Stefansson+H%2C+Rye+DB%2C+Hicks+A%2C+%27%27et+al%27%27&rft.pages=639%E2%80%9347&rft_id=info:pmid/17634447&rft_id=info:doi/10.1056%2FNEJMoa072743&rft_id=http%3A%2F%2Fcontent.nejm.org%2Fcgi%2Fpmidlookup%3Fview%3Dshort%26pmid%3D17634447%26promo%3DONFLNS19"> </span> </li>
<li id="_note-MayoAlgo">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> Mayo Clinic Algorithm also available as .pdf </li>
<li id="_note-pmid17516455"><strong>^</strong> <cite style="FONT-STYLE: normal">Oertel WH, Trenkwalder C, Zucconi M, <em>et al</em> (2007). "State of the art in restless legs syndrome therapy: Practice recommendations for treating restless legs syndrome". <em>Mov Disord</em>. doi:10.1002/mds.21545. PMID 17516455.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=State+of+the+art+in+restless+legs+syndrome+therapy%3A+Practice+recommendations+for+treating+restless+legs+syndrome&rft.jtitle=Mov+Disord&rft.date=2007&rft.au=Oertel+WH%2C+Trenkwalder+C%2C+Zucconi+M%2C+%27%27et+al%27%27&rft_id=info:pmid/17516455&rft_id=info:doi/10.1002%2Fmds.21545"> </span> </li>
<li id="_note-7"><strong>^</strong> "Medical Therapy for Restless Legs Syndrome may Trigger Compulsive Gambling", Mayo Clinic in Rochester, February 08, 2007 </li>
<li id="_note-8"><strong>^</strong> * RLS Foundation </li>
<li id="_note-9"><strong>^</strong> Marshall, Jessica, and Peter Aldhous. "Patient Groups Special." New Scientist, 10/26/06 </li>
<li id="_note-allen2005"><strong>^</strong> <cite style="FONT-STYLE: normal">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". <em>Arch. Intern. Med.</em> <strong>165</strong> (11): 1286-92. PMID 15956009.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Restless+legs+syndrome+prevalence+and+impact%3A+REST+general+population+study&rft.jtitle=Arch.+Intern.+Med.&rft.date=2005&rft.volume=165&rft.issue=11&rft.au=Allen+R%2C+Walters+A%2C+Montplaisir+J%2C+Hening+W%2C+Myers+A%2C+Bell+T%2C+Ferini-Strambi+L&rft.pages=1286-92&rft_id=info:pmid/15956009"> </span> </li>
<li id="_note-10"><strong>^</strong> Welcome - National Sleep Foundation. Retrieved on 2007-07-23. </li>
<li id="_note-WhoNamedIt">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <sup><em><strong>c</strong></em></sup> </li>
<li id="_note-11"><strong>^</strong> Ekbom, K.-A. Restless legs: a clinical study. Acta Med. Scand. (Suppl.) 158: 1-123, 1945. </li>
<li id="_note-12"><strong>^</strong> Restless Legs Syndrome Fact Sheet </li>
</ol>
</div>
<p><a id="External_links" name="External_links"></a></p>
<h2><span class="mw-headline">External links</span></h2>
<ul>
<li><em><a class="external text" title="http://www.ninds.nih.gov/disorders/restless_legs" href="http://www.ninds.nih.gov/disorders/restless_legs" rel="nofollow">restless_legs</a></em> at <a title="National Institute of Neurological Disorders and Stroke" href="http://en.wikipedia.org/wiki/National_Institute_of_Neurological_Disorders_and_Stroke">NINDS</a> </li>
<li><em><a class="external text" title="http://www.medicinenet.com/restless_leg_syndrome/article.htm" href="http://www.medicinenet.com/restless_leg_syndrome/article.htm" rel="nofollow">"restless_leg_syndrome"</a></em> at <a title="WebMD" href="http://en.wikipedia.org/wiki/WebMD">medicinenet.com</a> </li>
<li><a class="external text" title="http://www.neuro.jhmi.edu/rls/aboutus.htm" href="http://www.neuro.jhmi.edu/rls/aboutus.htm" rel="nofollow">Center for RLS</a>, <a class="external text" title="http://www.neuro.jhmi.edu/rls/edu.htm" href="http://www.neuro.jhmi.edu/rls/edu.htm" rel="nofollow">education</a> at <a title="Johns Hopkins" href="http://en.wikipedia.org/wiki/Johns_Hopkins">Johns Hopkins</a> </li>
<li><a class="external text" title="http://health.ivillage.com/quicklinks_sleepdisorders/0,,b6fj76m5,00.html" href="http://health.ivillage.com/quicklinks_sleepdisorders/0,,b6fj76m5,00.html" rel="nofollow">Restless Leg Syndrome Treatment, Diagnosis, and Symptoms</a> at <a title="IVillage" href="http://en.wikipedia.org/wiki/IVillage">iVillage</a> </li>
<li><a class="external text" title="http://www.dmoz.org/Health/Conditions_and_Diseases/Sleep_Disorders/Restless_Legs_Syndrome//" href="http://www.dmoz.org/Health/Conditions_and_Diseases/Sleep_Disorders/Restless_Legs_Syndrome//" rel="nofollow">Restless legs syndrome</a> at the <a title="Open Directory Project" href="http://en.wikipedia.org/wiki/Open_Directory_Project">Open Directory Project</a> </li>
</ul>
<p>Many doctors express the view that the incidence of restless leg syndrome is exaggerated by manufacturers of drugs used to treat it.<sup class="reference" id="_ref-0">[1]</sup> Other physicians consider it a real entity that has specific diagnostic criteria. <sup class="reference" id="_ref-1">[2]</sup></p>
<p>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, which is very different. With a nervous tic, someone does not necessarily notice it, but in RLS it is very noticeable. With a nervous tic, someone may tap their leg or foot, but with RLS you feel an undescribable sensation in your legs that can most closely be compared to a burning, itching sensation in the muscles of the legs or arms.</p>
<p><br />
</p>
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<p> </p>
<h2><span class="mw-headline">Signs and symptoms</span></h2>
<p>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.</p>
<p>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 the treatment of both conditions affect dopamine levels in the brain. [1]</p>
<ul>
<li>"An urge to move, usually due to uncomfortable sensations that occur primarily in the legs." </li>
</ul>
<p>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.</p>
<ul>
<li>"Motor restlessness, expressed as activity, that relieves the urge to move." </li>
</ul>
<p>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.</p>
<ul>
<li>"Worsening of symptoms by relaxation." </li>
</ul>
<p>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.</p>
<ul>
<li>"Variability over the course of the day-night cycle, with symptoms worse in the evening and early in the night." </li>
</ul>
<p>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.</p>
<p> </p>
<h3><span class="mw-headline">NIH criteria</span></h3>
<p>In 2003, a National Institutes of Health (NIH) consensus panel modified their criteria to include the following:</p>
<ul>
<li>(1) an urge to move the limbs with or without sensations </li>
<li>(2) worsening at rest </li>
<li>(3) improvement with activity </li>
<li>(4) worsening in the evening or night.<sup class="reference" id="_ref-2">[3]</sup> </li>
</ul>
<p>RLS is either primary or secondary.</p>
<ul>
<li>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. </li>
</ul>
<ul>
<li>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. </li>
</ul>
<p> </p>
<h2><span class="mw-headline">Causes</span></h2>
<p>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.</p>
<p>Hypoglycemia has also been found to worsen RLS symptoms.<sup class="reference" id="_ref-pmid9613772_0">[4]</sup> 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. Some doctors believe it is caused by irregular electrical impulses from the brain.</p>
<p>Both primary and secondary RLS can be worsened by surgery of any kind, however back surgery or injury can be associated with causing RLS.<sup class="reference" id="_ref-pmid15830971_0">[5]</sup> RLS can worsen in pregnancy. <sup class="reference" id="_ref-pmid3147073_0">[6]</sup></p>
<p> </p>
<h3><span class="mw-headline">Genetics</span></h3>
<p>40% of cases of RLS are familial and are inherited in an autosomal dominant fashion with variable penetrance.</p>
<p>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).<sup class="reference" id="_ref-3">[7]</sup> 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.<sup class="reference" id="_ref-4">[8]</sup><sup class="reference" id="_ref-5">[9]</sup> Various studies suggest chromosome 12q may indicate susceptibility to RLS.<sup class="reference" id="_ref-6">[10]</sup></p>
<p>There is also some evidence that periodic limb movements in sleep may be associated with the iron-regulating <em>BTBD9</em> at 6p21.2.<sup class="reference" id="_ref-pmid17634447_0">[11]</sup></p>
<p> </p>
<h2><span class="mw-headline">Diagnosis</span></h2>
<p><font size="2"></font></p>
<h2><span class="mw-headline">Prevention</span></h2>
<p><font size="2"></font></p>
<h2><span class="mw-headline">Treatment</span></h2>
<p>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.<sup class="reference" id="_ref-MayoAlgo_0">[12]</sup> 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.</p>
<p> </p>
<h3> <span class="mw-headline">Iron supplements</span></h3>
<p>According to some guidelines<sup class="noprint Template-Fact"><span title="This claim needs references to reliable sources since December 2007" style="WHITE-SPACE: nowrap">[<em>citation needed</em>]</span></sup>, 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.<sup class="reference" id="_ref-pmid17516455_0">[13]</sup></p>
<p> </p>
<h3><span class="mw-headline">Pharmaceuticals</span></h3>
<p>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,<sup class="reference" id="_ref-MayoAlgo_1">[12]</sup> medication from four categories:</p>
<ol>
<li>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. It was approved for sale in the EU in 2007. 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.<sup class="reference" id="_ref-7">[14]</sup> </li>
<li>Opioids such as propoxyphene, oxycodone, or methadone, etc. </li>
<li>Benzodiazepines, which often assist in staying asleep and reducing awakenings from the movements </li>
<li>Anticonvulsants, which often help people who experience the RLS sensations as painful, such as gabapentin </li>
</ol>
<p>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 <sup class="reference" id="_ref-8">[15]</sup> received 44% of its $1.4 million in funding from these pharmaceutical groups<sup class="reference" id="_ref-9">[16]</sup></p>
<p> </p>
<h2><span class="mw-headline">Prognosis</span></h2>
<p><font size="2"></font></p>
<h2><span class="mw-headline">Epidemiology</span></h2>
<p>Restless leg syndrome affects an estimated 2.7% of the general population in the U.S.A., but claims about the prevalence of RLS can be confusing because its severity varies enormously between individual sufferers; only a minority of sufferers experience daily or severe symptoms.<sup class="reference" id="_ref-allen2005_0">[17]</sup></p>
<p>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 experience 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).</p>
<p>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.<sup class="reference" id="_ref-10">[18]</sup></p>
<p> </p>
<h2><span class="mw-headline">History</span></h2>
<p>Earlier studies were done by Thomas Willis (1622-1675) and by Theodor Wittmaack.<sup class="reference" id="_ref-WhoNamedIt_0">[19]</sup> Another early description of the disease and its symptoms were made by George Miller Beard (1839-1883).<sup class="reference" id="_ref-WhoNamedIt_1">[19]</sup> In a 1945 publication titled 'Restless Legs', Karl-Axel Ekbom described the disease and presented eight cases used for his studies.<sup class="reference" id="_ref-11">[20]</sup></p>
<p>As with many diseases with diffuse symptoms, there is controversy among physicians as to whether RLS is a distinct syndrome. The US National Institute of Neurological Disorders and Stroke publishes an information sheet <sup class="reference" id="_ref-12">[21]</sup> 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 (SNS) response that could be caused by any number of physical or emotional factors<sup class="noprint Template-Fact"><span title="This claim needs references to reliable sources since August 2007" style="WHITE-SPACE: nowrap">[<em>citation needed</em>]</span></sup>. Other clinicians associate it with lumbosacral spinal subluxations and life stress.<sup class="noprint Template-Fact"><span title="This claim needs references to reliable sources since August 2007" style="WHITE-SPACE: nowrap">[<em>citation needed</em>]</span></sup></p>
<p>The UK support group for RLS calls itself the "Ekbom support group" and explains that RLS and "Ekbom's Syndrome" are two names for the same condition. 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. <sup class="reference" id="_ref-WhoNamedIt_2">[19]</sup></p>
<p> </p>
<h2><span class="mw-headline">See also</span></h2>
<ul>
<li>Actigraphy </li>
<li>Parasomnia </li>
<li>Disease mongering </li>
<li>Akathisia: A similar condition. </li>
</ul>
<p> </p>
<h2><span class="mw-headline">References</span></h2>
<div class="references-small" style="column-count: 2; -moz-column-count: 2; -webkit-column-count: 2">
<ol class="references">
<li id="_note-0"><strong>^</strong> <cite style="FONT-STYLE: normal">Woloshin S, Schwartz L (2006). "Giving legs to restless legs: a case study of how the media helps make people sick". <em>PLoS Med.</em> <strong>3</strong> (4): e170. PMID 16597175.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Giving+legs+to+restless+legs%3A+a+case+study+of+how+the+media+helps+make+people+sick&rft.jtitle=PLoS+Med.&rft.date=2006&rft.volume=3&rft.issue=4&rft.au=Woloshin+S%2C+Schwartz+L&rft.pages=e170&rft_id=info:pmid/16597175&rft_id=http%3A%2F%2Fdx.doi.org%2F10.1371%2Fjournal.pmed.0030170"> </span> </li>
<li id="_note-1"><strong>^</strong> <cite style="FONT-STYLE: normal">Montplaisir J; Boucher S; Nicolas A; Lesperance P; Gosselin A; Rompré P; Lavigne G (1998). "{{{title}}}". <em>Movement disorders</em> <strong>13</strong> (2): 324-9. PMID 9539348.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Movement+disorders&rft.date=1998&rft.volume=13&rft.issue=2&rft.au=Montplaisir+J%3B+Boucher+S%3B+Nicolas+A%3B+Lesperance+P%3B+Gosselin+A%3B+Rompr%C3%A9+P%3B+Lavigne+G&rft.pages=324-9&rft_id=info:pmid/9539348&rft_id=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fsites%2Fentrez%3Fdb%3DPubMed%26cmd%3Dretrieve%26dopt%3DAbstractPlus%26list_uids%3D9539348"> </span> </li>
<li id="_note-2"><strong>^</strong> <cite style="FONT-STYLE: normal">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.". <em>Sleep Med</em> <strong>4</strong> (2): 101-19. PMID 14592341.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Restless+legs+syndrome%3A+diagnostic+criteria%2C+special+considerations%2C+and+epidemiology.+A+report+from+the+restless+legs+syndrome+diagnosis+and+epidemiology+workshop+at+the+National+Institutes+of+Health.&rft.jtitle=Sleep+Med&rft.date=2003&rft.volume=4&rft.issue=2&rft.au=Allen+R%2C+Picchietti+D%2C+Hening+W%2C+Trenkwalder+C%2C+Walters+A%2C+Montplaisi+J&rft.pages=101-19"> </span> </li>
<li id="_note-pmid9613772"><strong>^</strong> <cite style="FONT-STYLE: normal">Kurlan R (1998). "Postprandial (reactive) hypoglycemia and restless leg syndrome: related neurologic disorders?". <em>Mov. Disord.</em> <strong>13</strong> (3): 619-20. doi:10.1002/mds.870130349. PMID 9613772.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Postprandial+%28reactive%29+hypoglycemia+and+restless+leg+syndrome%3A+related+neurologic+disorders%3F&rft.jtitle=Mov.+Disord.&rft.date=1998&rft.volume=13&rft.issue=3&rft.au=Kurlan+R&rft.pages=619-20&rft_id=info:pmid/9613772&rft_id=info:doi/10.1002%2Fmds.870130349"> </span> </li>
<li id="_note-pmid15830971"><strong>^</strong> <cite style="FONT-STYLE: normal">Crotti FM, Carai A, Carai M, Sgaramella E, Sias W (2005). "Entrapment of crural branches of the common peroneal nerve". <em>Acta Neurochir. Suppl.</em> <strong>92</strong>: 69-70. PMID 15830971.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Entrapment+of+crural+branches+of+the+common+peroneal+nerve&rft.jtitle=Acta+Neurochir.+Suppl.&rft.date=2005&rft.volume=92&rft.au=Crotti+FM%2C+Carai+A%2C+Carai+M%2C+Sgaramella+E%2C+Sias+W&rft.pages=69-70&rft_id=info:pmid/15830971"> </span> </li>
<li id="_note-pmid3147073"><strong>^</strong> <cite style="FONT-STYLE: normal">McParland P, Pearce JM (1988). "Restless leg syndrome in pregnancy". <em>BMJ</em> <strong>297</strong> (6662): 1543. PMID 3147073.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Restless+leg+syndrome+in+pregnancy&rft.jtitle=BMJ&rft.date=1988&rft.volume=297&rft.issue=6662&rft.au=McParland+P%2C+Pearce+JM&rft.pages=1543&rft_id=info:pmid/3147073"> </span> </li>
<li id="_note-3"><strong>^</strong> <cite style="FONT-STYLE: normal">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.". <em>Neurology</em> <strong>61</strong> (3): 304-9. PMID 12913188.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Neuropathological+examination+suggests+impaired+brain+iron+acquisition+in+restless+legs+syndrome.&rft.jtitle=Neurology&rft.date=2003&rft.volume=61&rft.issue=3&rft.au=Connor+J%2C+Boyer+P%2C+Menzies+S%2C+Dellinger+B%2C+Allen+R%2C+Ondo+W%2C+Earley+C&rft.pages=304-9"> </span> </li>
<li id="_note-4"><strong>^</strong> <cite style="FONT-STYLE: normal">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.". <em>Am J Hum Genet</em> <strong>69</strong> (6): 1266-70. PMID 11704926.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identification+of+a+major+susceptibility+locus+for+restless+legs+syndrome+on+chromosome+12q.&rft.jtitle=Am+J+Hum+Genet&rft.date=2001&rft.volume=69&rft.issue=6&rft.au=Desautels+A%2C+Turecki+G%2C+Montplaisir+J%2C+Sequeira+A%2C+Verner+A%2C+Rouleau+G&rft.pages=1266-70"> </span> </li>
<li id="_note-5"><strong>^</strong> <cite style="FONT-STYLE: normal">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.". <em>Ann Neurol</em> <strong>55</strong> (6): 887-91. PMID 15174026.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+14q+restless+legs+syndrome+locus+in+the+French+Canadian+population.&rft.jtitle=Ann+Neurol&rft.date=2004&rft.volume=55&rft.issue=6&rft.au=Levchenko+A%2C+Montplaisir+J%2C+Dub%C3%A9+M%2C+Riviere+J%2C+St-Onge+J%2C+Turecki+G%2C+Xiong+L%2C+Thibodeau+P%2C+Desautels+A%2C+Verlaan+D%2C+Rouleau+G&rft.pages=887-91"> </span> </li>
<li id="_note-6"><strong>^</strong> Christopher J. Earley, M.B., B.Ch., Ph.D., "Restless Legs Syndrome" <em>New England J Medicine</em> 2003; 348:2103 - 9. </li>
<li id="_note-pmid17634447"><strong>^</strong> <cite style="FONT-STYLE: normal">Stefansson H, Rye DB, Hicks A, <em>et al</em> (2007). "A genetic risk factor for periodic limb movements in sleep". <em>N. Engl. J. Med.</em> <strong>357</strong> (7): 639–47. doi:10.1056/NEJMoa072743. PMID 17634447.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+genetic+risk+factor+for+periodic+limb+movements+in+sleep&rft.jtitle=N.+Engl.+J.+Med.&rft.date=2007&rft.volume=357&rft.issue=7&rft.au=Stefansson+H%2C+Rye+DB%2C+Hicks+A%2C+%27%27et+al%27%27&rft.pages=639%E2%80%9347&rft_id=info:pmid/17634447&rft_id=info:doi/10.1056%2FNEJMoa072743&rft_id=http%3A%2F%2Fcontent.nejm.org%2Fcgi%2Fpmidlookup%3Fview%3Dshort%26pmid%3D17634447%26promo%3DONFLNS19"> </span> </li>
<li id="_note-MayoAlgo">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> Mayo Clinic Algorithm also available as .pdf </li>
<li id="_note-pmid17516455"><strong>^</strong> <cite style="FONT-STYLE: normal">Oertel WH, Trenkwalder C, Zucconi M, <em>et al</em> (2007). "State of the art in restless legs syndrome therapy: Practice recommendations for treating restless legs syndrome". <em>Mov Disord</em>. doi:10.1002/mds.21545. PMID 17516455.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=State+of+the+art+in+restless+legs+syndrome+therapy%3A+Practice+recommendations+for+treating+restless+legs+syndrome&rft.jtitle=Mov+Disord&rft.date=2007&rft.au=Oertel+WH%2C+Trenkwalder+C%2C+Zucconi+M%2C+%27%27et+al%27%27&rft_id=info:pmid/17516455&rft_id=info:doi/10.1002%2Fmds.21545"> </span> </li>
<li id="_note-7"><strong>^</strong> "Medical Therapy for Restless Legs Syndrome may Trigger Compulsive Gambling", Mayo Clinic in Rochester, February 08, 2007 </li>
<li id="_note-8"><strong>^</strong> * RLS Foundation </li>
<li id="_note-9"><strong>^</strong> Marshall, Jessica, and Peter Aldhous. "Patient Groups Special." New Scientist, 10/26/06 </li>
<li id="_note-allen2005"><strong>^</strong> <cite style="FONT-STYLE: normal">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". <em>Arch. Intern. Med.</em> <strong>165</strong> (11): 1286-92. PMID 15956009.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Restless+legs+syndrome+prevalence+and+impact%3A+REST+general+population+study&rft.jtitle=Arch.+Intern.+Med.&rft.date=2005&rft.volume=165&rft.issue=11&rft.au=Allen+R%2C+Walters+A%2C+Montplaisir+J%2C+Hening+W%2C+Myers+A%2C+Bell+T%2C+Ferini-Strambi+L&rft.pages=1286-92&rft_id=info:pmid/15956009"> </span> </li>
<li id="_note-10"><strong>^</strong> Welcome - National Sleep Foundation. Retrieved on 2007-07-23. </li>
<li id="_note-WhoNamedIt">^ <sup><em><strong>a</strong></em></sup> <sup><em><strong>b</strong></em></sup> <sup><em><strong>c</strong></em></sup> </li>
<li id="_note-11"><strong>^</strong> Ekbom, K.-A. Restless legs: a clinical study. Acta Med. Scand. (Suppl.) 158: 1-123, 1945. </li>
<li id="_note-12"><strong>^</strong> Restless Legs Syndrome Fact Sheet </li>
</ol>
</div>
<p><a id="External_links" name="External_links"></a></p>
<h2><span class="mw-headline">External links</span></h2>
<ul>
<li><em><a class="external text" title="http://www.ninds.nih.gov/disorders/restless_legs" href="http://www.ninds.nih.gov/disorders/restless_legs" rel="nofollow">restless_legs</a></em> at <a title="National Institute of Neurological Disorders and Stroke" href="http://en.wikipedia.org/wiki/National_Institute_of_Neurological_Disorders_and_Stroke">NINDS</a> </li>
<li><em><a class="external text" title="http://www.medicinenet.com/restless_leg_syndrome/article.htm" href="http://www.medicinenet.com/restless_leg_syndrome/article.htm" rel="nofollow">"restless_leg_syndrome"</a></em> at <a title="WebMD" href="http://en.wikipedia.org/wiki/WebMD">medicinenet.com</a> </li>
<li><a class="external text" title="http://www.neuro.jhmi.edu/rls/aboutus.htm" href="http://www.neuro.jhmi.edu/rls/aboutus.htm" rel="nofollow">Center for RLS</a>, <a class="external text" title="http://www.neuro.jhmi.edu/rls/edu.htm" href="http://www.neuro.jhmi.edu/rls/edu.htm" rel="nofollow">education</a> at <a title="Johns Hopkins" href="http://en.wikipedia.org/wiki/Johns_Hopkins">Johns Hopkins</a> </li>
<li><a class="external text" title="http://health.ivillage.com/quicklinks_sleepdisorders/0,,b6fj76m5,00.html" href="http://health.ivillage.com/quicklinks_sleepdisorders/0,,b6fj76m5,00.html" rel="nofollow">Restless Leg Syndrome Treatment, Diagnosis, and Symptoms</a> at <a title="IVillage" href="http://en.wikipedia.org/wiki/IVillage">iVillage</a> </li>
<li><a class="external text" title="http://www.dmoz.org/Health/Conditions_and_Diseases/Sleep_Disorders/Restless_Legs_Syndrome//" href="http://www.dmoz.org/Health/Conditions_and_Diseases/Sleep_Disorders/Restless_Legs_Syndrome//" rel="nofollow">Restless legs syndrome</a> at the <a title="Open Directory Project" href="http://en.wikipedia.org/wiki/Open_Directory_Project">Open Directory Project</a> </li>
</ul>