Restless legs syndrome
Other namesWillis–Ekbom disease (WED),[1] Wittmaack–Ekbom syndrome
Sleep pattern of a person with restless legs syndrome (red) compared to a healthy sleep pattern (blue)
SpecialtySleep medicine
SymptomsUnpleasant feeling in the legs that briefly improves with moving them[2]
ComplicationsDaytime sleepiness, low energy, irritability, sadness[2]
Usual onsetMore common with older age[3]
Risk factorsLow iron levels, kidney failure, Parkinson's disease, diabetes mellitus, rheumatoid arthritis, pregnancy, certain medications[2][4][5]
Diagnostic methodBased on symptoms after ruling out other possible causes[6]
TreatmentLifestyle changes, medication[2]
MedicationDopamine agonists, levodopa, gabapentinoids, opioids[4][7][8][9]
Frequency2.5–15% (US)[4]

Restless legs syndrome (RLS), also known as Willis–Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs.[2][10] There is often an unpleasant feeling in the legs that improves somewhat by moving them.[2] This is often described as aching, tingling, or crawling in nature.[2] Occasionally, arms may also be affected.[2] The feelings generally happen when at rest and therefore can make it hard to sleep.[2] Due to the disturbance in sleep, people with RLS may be sleepy during the day, have low energy, and feel irritable or depressed.[2] Additionally, many have limb twitching during sleep, a condition known as periodic limb movement disorder.[11] RLS is not the same as habitual foot-tapping or leg-rocking.[12]

Risk factors for RLS include low iron levels, kidney failure, Parkinson's disease, diabetes mellitus, rheumatoid arthritis, pregnancy and celiac disease.[2][4][13] A number of medications may also trigger the disorder including antidepressants, antipsychotics, antihistamines, and calcium channel blockers.[5] Restless leg syndrome may either be early-onset, occurring before age 45, or late-onset, occurring after age 45. Early-onset cases tend to progress more slowly and involve fewer comorbidities, while cases in older patients may progress suddenly and alongside other conditions.[14]

Diagnosis is generally based on a person's symptoms after ruling out other potential causes.[6]

Restless legs syndrome may resolve if the underlying problem is addressed.[15] Otherwise treatment includes lifestyle changes and medication.[2] Lifestyle changes that may help include stopping alcohol and tobacco use, and sleep hygiene.[15] Medications used to treat RLS include dopamine agonists like pramipexole and gabapentinoids (α2δ ligands) like gabapentin.[4][7] RLS affects an estimated 2.5–15% of the American population.[4] Females are more commonly affected than males, and it becomes increasingly common with age.[3][1]

History

Sir Thomas Willis provided a medical description in 1672.[16] Willis emphasized the sleep disruption and limb movements experienced by people with RLS.

Subsequently, other descriptions of RLS were published, including by Theodor Wittmaack [de] (1861) (in relation to whom it is sometimes known as Wittmaack-Ekbom syndrome).[17]

In 1945, Karl-Axel Ekbom (1907–1977) provided a detailed and comprehensive report of this condition in his doctoral thesis, restless legs: clinical study of hitherto overlooked disease.[18] Ekbom coined the term "restless legs".

Ekbom's work was largely ignored until it was rediscovered by Arthur S. Walters and Wayne A. Hening in the 1980s. Subsequent landmark publications include 1995 and 2003 papers, which revised and updated the diagnostic criteria.[19][20]

Signs and symptoms

RLS sensations range from pain or an aching in the muscles, to "an itch you can't scratch", a "buzzing sensation", an unpleasant "tickle that won't stop", a "crawling" feeling, or limbs jerking while awake. The sensations typically begin or intensify during quiet wakefulness, such as when relaxing, reading, studying, or trying to sleep.[19]

It is a "spectrum disorder" with some people experiencing only a minor annoyance and others having major disruption of sleep and impairments in quality of life.[21]

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 childhood, and is a progressive disease for some, while the symptoms may remit in others.[22] In a survey among members of the Restless Legs Syndrome Foundation, it was found that up to 45% of patients had their first symptoms before the age of 20 years.[23]

RLS may contribute to higher rates of depression and anxiety disorders in RLS patients.[25]

Primary and secondary

RLS is categorized as either primary or secondary.

Causes

While the cause is generally unknown, it is believed to be caused by changes in the neurotransmitter dopamine[27] resulting in an abnormal use of iron by the brain.[1] RLS is often due to iron deficiency (low total body iron status)[1] and could be a sign of anemia caused by internal bleeding or bone marrow issues. Other associated conditions may include end-stage kidney disease and hemodialysis, folate deficiency, magnesium deficiency, sleep apnea, diabetes, peripheral neuropathy, Parkinson's disease, and certain autoimmune diseases, such as multiple sclerosis.[28] RLS can worsen in pregnancy, possibly due to elevated estrogen levels.[1][29] Use of alcohol, nicotine products, and caffeine may be associated with RLS.[1] A 2014 study from the American Academy of Neurology also found that reduced leg oxygen levels were strongly associated with restless legs syndrome symptom severity in untreated patients.[27]

ADHD

An association has been observed between attention deficit hyperactivity disorder (ADHD) and RLS or periodic limb movement disorder.[30] Both conditions appear to have links to dysfunctions related to the neurotransmitter dopamine, and common medications for both conditions among other systems, affect dopamine levels in the brain.[31] A 2005 study suggested that up to 44% of people with ADHD had comorbid (i.e. coexisting) RLS, and up to 26% of people with RLS had confirmed ADHD or symptoms of the condition.[32]

Medications

Certain medications may cause or worsen RLS, or cause it secondarily, including:[1]

Both primary and secondary RLS can be worsened by surgery of any kind; however, back surgery or injury can be associated with causing RLS.[36]

The cause vs. effect of certain conditions and behaviors observed in some patients (ex. excess weight, lack of exercise, depression or other mental illnesses) is not well established. Loss of sleep due to RLS could cause the conditions, or medication used to treat a condition could cause RLS.[37][38]

Genetics

More than 60% of cases of RLS are familial and are inherited in an autosomal dominant fashion with variable penetrance.[39]

Research and brain autopsies have implicated both dopaminergic system and iron insufficiency in the substantia nigra.[40] Iron is well understood to be an essential cofactor for the formation of L-dopa, the precursor of dopamine.

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

Three genes, MEIS1, BTBD9 and MAP2K5, were found to be associated to RLS.[53] Their role in RLS pathogenesis is still unclear. More recently, a fourth gene, PTPRD was found to be associated with RLS.[54]

There is also some evidence that periodic limb movements in sleep (PLMS) are associated with BTBD9 on chromosome 6p21.2,[55][56] MEIS1, MAP2K5/SKOR1, and PTPRD.[56] The presence of a positive family history suggests that there may be a genetic involvement in the etiology of RLS.

Mechanism

Although it is only partly understood, pathophysiology of restless legs syndrome may involve dopamine and iron system anomalies.[57][58] There is also a commonly acknowledged circadian rhythm explanatory mechanism associated with it, clinically shown simply by biomarkers of circadian rhythm, such as body temperature.[59] The interactions between impaired neuronal iron uptake and the functions of the neuromelanin-containing and dopamine-producing cells have roles in RLS development, indicating that iron deficiency might affect the brain dopaminergic transmissions in different ways.[60]

Medial thalamic nuclei may also have a role in RLS as part as the limbic system modulated by the dopaminergic system[61] which may affect pain perception.[62] Improvement of RLS symptoms occurs in people receiving low-dose dopamine agonists.[63]

Diagnosis

There are no specific tests for RLS, but non-specific laboratory tests are used to rule out other causes such as vitamin deficiencies. Five symptoms are used to confirm the diagnosis:[1]

The symptoms below are not essential, like the ones above, but occur commonly in RLS patients:[1][64]

According to the International Classification of Sleep Disorders (ICSD-3), the main symptoms have to be associated with a sleep disturbance or impairment in order to support RLS diagnosis.[65] As stated by this classification, RLS symptoms should begin or worsen when being inactive, be relieved when moving, should happen exclusively or mostly in the evening and at night, not be triggered by other medical or behavioral conditions, and should impair one's quality of life.[65][66] Generally, both legs are affected, but in some cases there is an asymmetry.

Differential diagnosis

The most common conditions that should be differentiated with RLS include leg cramps, positional discomfort, local leg injury, arthritis, leg edema, venous stasis, peripheral neuropathy, radiculopathy, habitual foot tapping/leg rocking, anxiety, myalgia, and drug-induced akathisia.[12]

Peripheral artery disease and arthritis can also cause leg pain but this usually gets worse with movement.[11]

There are less common differential diagnostic conditions included myelopathy, myopathy, vascular or neurogenic claudication, hypotensive akathisia, orthostatic tremor, painful legs, and moving toes.[12]

Treatment

If RLS is not linked to an underlying cause, its frequency may be reduced by lifestyle modifications such as adopting improving sleep hygiene, regular exercise, and stopping smoking.[67] Medications used may include dopamine agonists and gabapentinoids in those with daily restless legs syndrome.[1][35][7][8] In severe or refractory cases, opioids have been used.[68]

Treatment of RLS should not be considered until possible medical causes are ruled out. Secondary RLS may be cured if precipitating medical conditions (anemia) are managed effectively.[1]

Physical measures

Stretching the leg muscles can bring temporary relief.[19][69] Walking and moving the legs, as the name "restless legs" implies, brings temporary relief. In fact, those with RLS often have an almost uncontrollable need to walk and therefore relieve the symptoms while they are moving. Unfortunately, the symptoms usually return immediately after the moving and walking ceases.

Counter-stimulation from massage, a hot or cold compress, or a vibratory counter-stimulation device has been found to help some people with primary RLS to improve their sleep.[70][71]

Iron

There is some evidence that intravenous iron supplementation moderately improves restlessness for people with RLS.[72]

Medications

For those whose RLS disrupts or prevents sleep or regular daily activities, medication may be useful. Evidence supports the use of dopamine agonists including pramipexole, ropinirole, rotigotine, cabergoline, and pergolide.[7][73][74] They reduce symptoms, improve sleep quality and quality of life.[75] Levodopa is also effective.[76] However, pergolide and cabergoline are less recommended due to their association with increased risk of valvular heart disease.[77] Ropinirole has a faster onset with shorter duration.[78] Rotigotine is commonly used as a transdermal patch which continuously provides stable plasma drug concentrations, resulting in its particular therapeutic effect on patients with symptoms throughout the day.[78] A 2008 meta-analysis[needs update] found pramipexole to be better than ropinirole.[79]

There are, however, issues with the use of dopamine agonists including 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. In many cases, the longer dopamine agonists have been used, the higher the risk of augmentation and rebound as well as the severity of the symptoms. Patients may also develop dopamine dysregulation syndrome, meaning that they can experience an addictive pattern of dopamine replacement therapy. A 2007 study indicated that dopamine agonists used in restless legs syndrome can lead to an increase in compulsive gambling.[80] Patients may also exhibit other impulse-control disorders such as compulsive shopping and compulsive eating.[81] There are some indications that stopping the dopamine agonist treatment has an impact on the resolution or at least improvement of the impulse-control disorder, even though some people can be particularly exposed to dopamine agonist withdrawal syndrome.[81]

Gabapentinoids (α2δ ligands), including gabapentin, pregabalin, and gabapentin enacarbil, are also widely used in the treatment of RLS.[7][82] They are used as first-line treatments similarly to dopamine agonists, and as of 2019, guidelines have started to recommend gabapentinoids over dopamine agonists as initial therapy for RLS due to higher known risks of symptom augmentation with long-term dopamine agonist therapy.[83] Gabapentin enacarbil is approved by regulatory authorities for the treatment of RLS, whereas gabapentin and pregabalin are used off-label.[7] Data on gabapentinoids in the treatment of RLS are more limited compared to dopamine agonists.[84] However, based on available evidence, gabapentinoids are similarly effective to dopamine agonists in the treatment of RLS.[83][85][82]

Low doses of opioids are used in the treatment of severe and treatment-resistant cases and are recommended by multiple reputable medical guidelines.[7][8][86] The most commonly used agents are prolonged-release oxycodone and methadone, but other opioids, including tramadol, codeine, morphine, and hydrocodone, may also be considered.[7][87][8] Opioids are only indicated in severe cases that do not respond to other measures due to their very high abuse liability and high rate of side effects, which may include constipation, fatigue, and headache.[88][35] However, opioids are said to be highly effective for severe and refractory RLS, and can be helpful in well-selected individuals.[7][8][87]

Benzodiazepines, such as diazepam or clonazepam, are not generally recommended,[89] and their effectiveness is unknown or contradictory.[90][84] They, however, are sometimes still used as a second-line treatment,[91] as add-on agents.[90] Other treatments have also been explored, such as valproate, carbamazepine, perampanel, and dipyridamole, but are either not effective or have insufficient data to support their use.[84]

Placebo

Placebos provide a large benefit in terms of reduction of RLS symptoms.[92] This is thought to be due to positive expectancy effects and conditioning, which activate dopamine and opioid pathways in the brain.[92] Both dopamine agonists and opioids are used in and effective for the treatment of RLS, which is thought to be related to the effectiveness of placebos for the condition.[92] More than half of the benefit of RLS medications such as pramipexole and gabapentin enacarbil appears to be due to the placebo component based on clinical trial data.[93][94]

Prognosis

RLS symptoms may gradually worsen with age, although more slowly for those with the idiopathic form of RLS than for people who also have an associated medical condition.[95] Current therapies can control the disorder, minimizing symptoms and increasing periods of restful sleep. In addition, some people have remissions, periods in which symptoms decrease or disappear for days, weeks, or months, although symptoms usually eventually reappear.[95] Being diagnosed with RLS does not indicate or foreshadow another neurological disease, such as Parkinson's disease.[95] RLS symptoms can worsen over time when dopamine-related drugs are used for therapy, an effect called augmentation which may represent symptoms occurring throughout the day and affect movements of all limbs.[95] There is no cure for RLS.[95]

Epidemiology

RLS affects an estimated 2.5–15% of the American population.[4][96] A minority (around 2.7% of the population) experience daily or severe symptoms.[97] RLS is twice as common in women as in men,[98] and Caucasians are more prone to RLS than people of African descent.[96] RLS occurs in 3% of individuals from the Mediterranean or Middle Eastern regions, and in 1–5% of those from East Asia, indicating that different genetic or environmental factors, including diet, may play a role in the prevalence of this syndrome.[96][99] RLS diagnosed at an older age runs a more severe course.[69] RLS is even more common in individuals with iron deficiency, pregnancy, or end-stage kidney disease.[100][101] The National Sleep Foundation's 1998 Sleep in America poll showed that up to 25 percent of pregnant women developed RLS during the third trimester.[102] Poor general health is also linked.[103]

There are several risk factors for RLS, including old age, family history, and uremia. The prevalence of RLS tends to increase with age, as well as its severity and longer duration of symptoms. People with uremia receiving renal dialysis have a prevalence from 20% to 57%, while those having kidney transplant improve compared to those treated with dialysis.[104]

RLS can occur at all ages, although it typically begins in the third or fourth decade.[66] Genome‐wide association studies have now identified 19 risk loci associated with RLS.[105] Neurological conditions linked to RLS include Parkinson's disease, spinal cerebellar atrophy, spinal stenosis,[specify] lumbosacral radiculopathy and Charcot–Marie–Tooth disease type 2.[96]

Nomenclature

In 2013, the Restless Legs Syndrome Foundation renamed itself the Willis–Ekbom Disease Foundation; however, it reverted to its original name in 2015 “to better support its mission”.[106]

A point of confusion is that RLS and delusional parasitosis are entirely different conditions that have both been called "Ekbom syndrome", as both syndromes were described by the same person, Karl-Axel Ekbom.[107] Today, calling WED/RLS "Ekbom syndrome" is outdated usage, as the unambiguous names (WED or RLS) are preferred for clarity.

Controversy

Some doctors express the view that the incidence of restless legs syndrome is exaggerated by manufacturers of drugs used to treat it.[108] Others believe it is an underrecognized and undertreated disorder.[96] Further, GlaxoSmithKline (GSK) ran advertisements that, while not promoting off-licence use of their drug (ropinirole) for treatment of RLS, did link to the Ekbom Support Group website. That website contained statements advocating the use of ropinirole to treat RLS. The Association of the British Pharmaceutical Industry (ABPI) ruled against GSK in this case.[109]

Research

Different measurements have been used to evaluate treatments in RLS. Most of them are based on subjective rating scores, such as IRLS rating scale (IRLS), Clinical Global Impression (CGI), Patient Global Impression (PGI), and Quality of life (QoL).[110] These questionnaires provide information about the severity and progress of the disease, as well as the person's quality of life and sleep.[110] Polysomnography (PSG) and actigraphy (both related to sleep parameters) are more objective resources that provide evidences of sleep disturbances associated with RLS symptoms.[110]

See also

References

  1. ^ a b c d e f g h i j k l m "Restless Legs Syndrome Fact Sheet | National Institute of Neurological Disorders and Stroke". Ninds.nih.gov. Archived from the original on 28 July 2017. Retrieved 7 July 2019.
  2. ^ a b c d e f g h i j k l "What Is Restless Legs Syndrome?". NHLBI. November 1, 2010. Archived from the original on 21 August 2016. Retrieved 19 August 2016.
  3. ^ a b "Who Is at Risk for Restless Legs Syndrome?". NHLBI. November 1, 2010. Archived from the original on 26 August 2016. Retrieved 19 August 2016.
  4. ^ a b c d e f g Ramar, Kannan; Olson, Eric J. (15 August 2013). "Management of common sleep disorders". American Family Physician. 88 (4): 231–238. PMID 23944726. Archived from the original on 27 February 2024. Retrieved 26 November 2022.
  5. ^ a b "What Causes Restless Legs Syndrome?". NHLBI. November 1, 2010. Archived from the original on 20 August 2016. Retrieved 19 August 2016.
  6. ^ a b "How Is Restless Legs Syndrome Diagnosed?". NHLBI. November 1, 2010. Archived from the original on 27 August 2016. Retrieved 19 August 2016.
  7. ^ a b c d e f g h i Garcia-Borreguero D, Silber MH, Winkelman JW, Högl B, Bainbridge J, Buchfuhrer M, Hadjigeorgiou G, Inoue Y, Manconi M, Oertel W, Ondo W, Winkelmann J, Allen RP (May 2016). "Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation". Sleep Med. 21: 1–11. doi:10.1016/j.sleep.2016.01.017. PMID 27448465.
  8. ^ a b c d e Silber MH, Buchfuhrer MJ, Earley CJ, Koo BB, Manconi M, Winkelman JW (July 2021). "The Management of Restless Legs Syndrome: An Updated Algorithm". Mayo Clin Proc. 96 (7): 1921–1937. doi:10.1016/j.mayocp.2020.12.026. PMID 34218864. S2CID 235733578.
  9. ^ Gossard, Thomas R.; Trotti, Lynn Marie; Videnovic, Aleksandar; St Louis, Erik K. (20 April 2021). "Restless Legs Syndrome: Contemporary Diagnosis and Treatment" (PDF). Neurotherapeutics. 18 (1): 140–155. doi:10.1007/s13311-021-01019-4. PMC 8116476. PMID 33880737. Archived (PDF) from the original on 27 January 2023. Retrieved 27 January 2023.
  10. ^ "Restless Legs Syndrome Information Page | National Institute of Neurological Disorders and Stroke". Ninds.nih.gov. Archived from the original on 8 October 2019. Retrieved 7 July 2019.
  11. ^ a b "What Are the Signs and Symptoms of Restless Legs Syndrome?". NHLBI. November 1, 2010. Archived from the original on 27 August 2016. Retrieved 19 August 2016.
  12. ^ a b c Allen, Richard P.; Picchietti, Daniel L.; Garcia-Borreguero, Diego; Ondo, William G.; Walters, Arthur S.; Winkelman, John W.; Zucconi, Marco; Ferri, Raffaele; Trenkwalder, Claudia; Lee, Hochang B. (August 2014). "Restless legs syndrome/Willis–Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria – history, rationale, description, and significance". Sleep Medicine. 15 (8): 860–873. doi:10.1016/j.sleep.2014.03.025. PMID 25023924. Archived from the original on 2024-02-27. Retrieved 2022-04-09.
  13. ^ Zis P, Hadjivassiliou M (2019). "Treatment of Neurological Manifestations of Gluten Sensitivity and Coeliac Disease". Curr Treat Options Neurol (Review). 21 (3): 10. doi:10.1007/s11940-019-0552-7. PMID 30806821.
  14. ^ Didato, G.; Di Giacomo, R.; Rosa, G. J.; Dominese, A.; De Curtis, M.; Lanteri, P. (2020). "Restless Legs Syndrome across the Lifespan: Symptoms, Pathophysiology, Management and Daily Life Impact of the Different Patterns of Disease Presentation". International Journal of Environmental Research and Public Health. 17 (10): 3658. doi:10.3390/ijerph17103658. PMC 7277795. PMID 32456058.
  15. ^ a b "How Is Restless Legs Syndrome Treated?". NHLBI. November 1, 2010. Archived from the original on 27 August 2016. Retrieved 19 August 2016.
  16. ^ Coccagna, G; Vetrugno, R; Lombardi, C; Provini, F (2004). "Restless legs syndrome: an historical note". Sleep Medicine. 5 (3): 279–83. doi:10.1016/j.sleep.2004.01.002. PMID 15165536.
  17. ^ Behrman, Simon (21 June 1958). "Disturbed Relaxation of Limbs". BMJ. 1 (5085): 1454–1457. doi:10.1136/bmj.1.5085.1454. PMC 2029296. PMID 13536531. Archived from the original on 17 November 2023. Retrieved 17 November 2023.
  18. ^ Ekrbom, Karl-Axel (2009). "PREFACE". Acta Medica Scandinavica. 121: 1–123. doi:10.1111/j.0954-6820.1945.tb11970.x.
  19. ^ a b c Allen, R; Picchietti, D; Hening, WA; Trenkwalder, C; Walters, AS; Montplaisi, J; Restless Legs Syndrome Diagnosis Epidemiology workshop at the National Institutes of Health; International Restless Legs Syndrome Study Group (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 Medicine. 4 (2): 101–19. doi:10.1016/S1389-9457(03)00010-8. PMID 14592341.
  20. ^ Walters, Arthur S.; Aldrich, Michael S.; Allen, Richard; Ancoli-Israel, Sonia; Buchholz, David; Chokroverty, Sudhansu; Coccagna, Giorgio; Earley, Christopher; Ehrenberg, Bruce; Feest, T. G.; Hening, Wayne; Kavey, Neil; Lavigne, Gilles; Lipinski, Joseph; Lugaresi, Elio; Montagna, Pasquale; Montplaisir, Jacques; Mosko, Sarah S.; Oertel, Wolfgang; Picchietti, Daniel; Pollmächer, Thomas; Shafor, Renata; Smith, Robert C.; Telstad, Wenche; Trenkwalder, Claudia; Von Scheele, Christian; Walters, Arthur S.; Ware, J. Catesby; Zucconi, Marco (1995). "Toward a better definition of the restless legs syndrome". Movement Disorders. 10 (5): 634–42. doi:10.1002/mds.870100517. PMID 8552117. S2CID 22970514.
  21. ^ Earley, Christopher J.; Silber, Michael H. (2010). "Restless legs syndrome: Understanding its consequences and the need for better treatment". Sleep Medicine. 11 (9): 807–15. doi:10.1016/j.sleep.2010.07.007. PMID 20817595.
  22. ^ Xiong, L.; Montplaisir, J.; Desautels, A.; Barhdadi, A.; Turecki, G.; Levchenko, A.; Thibodeau, P.; Dubé, M. P.; Gaspar, C.; Rouleau, GA (2010). "Family Study of Restless Legs Syndrome in Quebec, Canada: Clinical Characterization of 671 Familial Cases". Archives of Neurology. 67 (5): 617–22. doi:10.1001/archneurol.2010.67. PMID 20457962.
  23. ^ Walters, A. S.; Hickey, K.; Maltzman, J.; Verrico, T.; Joseph, D.; Hening, W.; Wilson, V.; Chokroverty, S. (1996). "A questionnaire study of 138 patients with restless legs syndrome: The 'Night-Walkers' survey". Neurology. 46 (1): 92–5. doi:10.1212/WNL.46.1.92. PMID 8559428. S2CID 25278952.
  24. ^ Phillips, B.; Hening, W.; Britz, P. (2006). "Prevalence and correlates of restless legs syndrome: results from the 2005 National Sleep Foundation Poll". Chest. 129 (1): 76–80. doi:10.1378/chest.129.1.76. PMID 16424415.
  25. ^ Becker, Philip M.; Sharon, Denise (15 July 2014). "Mood Disorders in Restless Legs Syndrome (Willis-Ekbom Disease)". The Journal of Clinical Psychiatry. 75 (7): e679–e694. doi:10.4088/jcp.13r08692. PMID 25093484.
  26. ^ "Restless legs syndrome". NHS inform. Archived from the original on 2023-11-06. Retrieved 2023-11-06.
  27. ^ a b St. Louis, E. K. (27 May 2014). "New evidence for reduced leg oxygen levels in restless legs syndrome". Neurology. 82 (21): e185–e187. doi:10.1212/WNL.0000000000000513. PMID 24862901. S2CID 207107060.
  28. ^ MedlinePlus Encyclopedia: Restless legs syndrome
  29. ^ Gupta, R.; Dhyani, M.; Kendzerska, T.; Pandi-Perumal, S. R.; BaHammam, A. S.; Srivanitchapoom, P.; Pandey, S.; Hallett, M. (May 2016). "Restless legs syndrome and pregnancy: prevalence, possible pathophysiological mechanisms and treatment". Acta Neurologica Scandinavica. 133 (5): 320–329. doi:10.1111/ane.12520. PMC 5562408. PMID 26482928.
  30. ^ Walters, A. S.; Silvestri, R; Zucconi, M; Chandrashekariah, R; Konofal, E (2008). "Review of the Possible Relationship and Hypothetical Links Between Attention Deficit Hyperactivity Disorder (ADHD) and the Simple Sleep Related Movement Disorders, Parasomnias, Hypersomnias, and Circadian Rhythm Disorders". Journal of Clinical Sleep Medicine. 4 (6): 591–600. doi:10.5664/jcsm.27356. PMC 2603539. PMID 19110891.
  31. ^ "Attention deficit hyperactivity disorder – Other Disorders Associated with ADHD". University of Maryland Medical Center. 2008. Archived from the original on 2008-05-07. Retrieved 27 October 2021.
  32. ^ Cortese, S; Konofal, E; Lecendreux, M; Arnulf, I; Mouren, MC; Darra, F; Dalla Bernardina, B (2005). "Restless legs syndrome and attention-deficit/hyperactivity disorder: A review of the literature". Sleep. 28 (8): 1007–13. doi:10.1093/sleep/28.8.1007. PMID 16218085.
  33. ^ a b c Buchfuhrer, MJ (October 2012). "Strategies for the treatment of restless legs syndrome". Neurotherapeutics (Review). 9 (4): 776–90. doi:10.1007/s13311-012-0139-4. PMC 3480566. PMID 22923001.
  34. ^ Neiman, J.; Lang, A. E.; Fornazzari, L.; Carlen, P. L. (May 1990). "Movement disorders in alcoholism: A review". Neurology. 40 (5): 741–746. doi:10.1212/wnl.40.5.741. PMID 2098000. S2CID 8940680.
  35. ^ a b c Trenkwalder, Claudia; Zieglgänsberger, Walter; Ahmedzai, Sam H.; Högl, Birgit (March 2017). "Pain, opioids, and sleep: implications for restless legs syndrome treatment". Sleep Medicine. 31: 78–85. doi:10.1016/j.sleep.2016.09.017. PMID 27964861.
  36. ^ Crotti, Francesco Maria; Carai, A.; Carai, M.; Sgaramella, E.; Sias, W. (2005). "Entrapment of crural branches of the common peroneal nerve". Advanced Peripheral Nerve Surgery and Minimal Invasive Spinal Surgery. Acta Neurochirurgica. Vol. 97. pp. 69–70. doi:10.1007/3-211-27458-8_15. ISBN 978-3-211-23368-9. PMID 15830971.
  37. ^ Aukerman, M. M.; Aukerman, D.; Bayard, M.; Tudiver, F.; Thorp, L.; Bailey, B. (1 September 2006). "Exercise and Restless Legs Syndrome: A Randomized Controlled Trial". The Journal of the American Board of Family Medicine. 19 (5): 487–493. doi:10.3122/jabfm.19.5.487. PMID 16951298. S2CID 34376834.
  38. ^ Phillips, Barbara A.; Britz, Pat; Hening, Wayne (1 October 2005). "The NSF 2005 Sleep in American Poll and those at risk for RLS". Chest. 128 (4): 133S. doi:10.1378/chest.128.4_MeetingAbstracts.133S. Gale A138392919 ProQuest 200457669.
  39. ^ Lavigne, GJ; Montplaisir, JY (1994). "Restless legs syndrome and sleep bruxism: prevalence and association among Canadians". Sleep. 17 (8): 739–43. PMID 7701186.
  40. ^ Connor, J.R.; Boyer, P.J.; Menzies, S.L.; Dellinger, B.; Allen, R.P.; Ondo, W.G.; Earley, C.J. (2003). "Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome". Neurology. 61 (3): 304–9. doi:10.1212/01.WNL.0000078887.16593.12. PMID 12913188. S2CID 44703083.
  41. ^ Desautels, Alex; Turecki, Gustavo; Montplaisir, Jacques; Sequeira, Adolfo; Verner, Andrei; Rouleau, Guy A. (2001). "Identification of a Major Susceptibility Locus for Restless Legs Syndrome on Chromosome 12q". The American Journal of Human Genetics. 69 (6): 1266–70. doi:10.1086/324649. PMC 1235538. PMID 11704926.
  42. ^ Desautels, A.; Turecki, G; Montplaisir, J; Xiong, L; Walters, AS; Ehrenberg, BL; Brisebois, K; Desautels, AK; Gingras, Y; Johnson, WG; Lugaresi, E; Coccagna, G; Picchietti, DL; Lazzarini, A; Rouleau, GA (2005). "Restless Legs Syndrome: Confirmation of Linkage to Chromosome 12q, Genetic Heterogeneity, and Evidence of Complexity". Archives of Neurology. 62 (4): 591–6. doi:10.1001/archneur.62.4.591. PMID 15824258.
  43. ^ Winkelmann, Juliane; Lichtner, Peter; Pütz, Benno; Trenkwalder, Claudia; Hauk, Stephanie; Meitinger, Thomas; Strom, Tim; Muller-Myhsok, Bertram (2006). "Evidence for further genetic locus heterogeneity and confirmation of RLS-1 in restless legs syndrome". Movement Disorders. 21 (1): 28–33. doi:10.1002/mds.20627. PMID 16124010. S2CID 25736900.
  44. ^ Bonati, M. T. (2003). "Autosomal dominant restless legs syndrome maps on chromosome 14q". Brain. 126 (6): 1485–92. doi:10.1093/brain/awg137. PMID 12764067.
  45. ^ Levchenko, Anastasia; Montplaisir, Jacques-Yves; Dubé, Marie-Pierre; Riviere, Jean-Baptiste; St-Onge, Judith; Turecki, Gustavo; Xiong, Lan; Thibodeau, Pascale; Desautels, Alex; Verlaan, Dominique J.; Rouleau, Guy A. (2004). "The 14q restless legs syndrome locus in the French Canadian population". Annals of Neurology. 55 (6): 887–91. doi:10.1002/ana.20140. PMID 15174026. S2CID 31001901.
  46. ^ Kemlink, David; Polo, Olli; Montagna, Pasquale; Provini, Federica; Stiasny-Kolster, Karin; Oertel, Wolfgang; De Weerd, Al; Nevsimalova, Sona; Sonka, Karel; Högl, Birgit; Frauscher, Birgit; Poewe, Werner; Trenkwalder, Claudia; Pramstaller, Peter P.; Ferini-Strambi, Luigi; Zucconi, Marco; Konofal, Eric; Arnulf, Isabelle; Hadjigeorgiou, Georgios M.; Happe, Svenja; Klein, Christine; Hiller, Anja; Lichtner, Peter; Meitinger, Thomas; Müller-Myshok, Betram; Winkelmann, Juliane (2007). "Family-based association study of the restless legs syndrome loci 2 and 3 in a European population". Movement Disorders. 22 (2): 207–12. doi:10.1002/mds.21254. PMID 17133505. S2CID 34801702.
  47. ^ Chen, Shenghan; Ondo, William G.; Rao, Shaoqi; Li, Lin; Chen, Qiuyun; Wang, Qing (2004). "Genomewide Linkage Scan Identifies a Novel Susceptibility Locus for Restless Legs Syndrome on Chromosome 9p". The American Journal of Human Genetics. 74 (5): 876–885. doi:10.1086/420772. PMC 1181982. PMID 15077200.
  48. ^ Liebetanz, K. M.; Winkelmann, J; Trenkwalder, C; Pütz, B; Dichgans, M; Gasser, T; Müller-Myhsok, B (2006). "RLS3: Fine-mapping of an autosomal dominant locus in a family with intrafamilial heterogeneity". Neurology. 67 (2): 320–321. doi:10.1212/01.wnl.0000224886.65213.b5. PMID 16864828. S2CID 20796797.
  49. ^ Lohmann-Hedrich, K.; Neumann, A.; Kleensang, A.; Lohnau, T.; Muhle, H.; Djarmati, A.; König, I. R.; Pramstaller, P. P.; Schwinger, E.; Kramer, P. L.; Ziegler, A.; Stephani, U.; Klein, C. (2008). "Evidence for linkage of restless legs syndrome to chromosome 9p: Are there two distinct loci?". Neurology. 70 (9): 686–694. doi:10.1212/01.wnl.0000282760.07650.ba. PMID 18032746. S2CID 24889954.
  50. ^ Levchenko, A.; Provost, S; Montplaisir, JY; Xiong, L; St-Onge, J; Thibodeau, P; Rivière, JB; Desautels, A; Turecki, G; Dubé, M. P.; Rouleau, G. A. (2006). "A novel autosomal dominant restless legs syndrome locus maps to chromosome 20p13". Neurology. 67 (5): 900–901. doi:10.1212/01.wnl.0000233991.20410.b6. PMID 16966564. S2CID 20555259.
  51. ^ Pichler, Irene; Marroni, Fabio; Beu Volpato, Claudia; Gusella, James F.; Klein, Christine; Casari, Giorgio; De Grandi, Alessandro; Pramstaller, Peter P. (2006). "Linkage Analysis Identifies a Novel Locus for Restless Legs Syndrome on Chromosome 2q in a South Tyrolean Population Isolate". The American Journal of Human Genetics. 79 (4): 716–23. doi:10.1086/507875. PMC 1592574. PMID 16960808.
  52. ^ Levchenko, Anastasia; Montplaisir, Jacques-Yves; Asselin, GéRaldine; Provost, Sylvie; Girard, Simon L.; Xiong, Lan; Lemyre, Emmanuelle; St-Onge, Judith; Thibodeau, Pascale; Desautels, Alex; Turecki, Gustavo; Gaspar, Claudia; Dubé, Marie-Pierre; Rouleau, Guy A. (2009). "Autosomal-dominant locus for restless legs syndrome in French-Canadians on chromosome 16p12.1". Movement Disorders. 24 (1): 40–50. doi:10.1002/mds.22263. PMID 18946881. S2CID 7796597.
  53. ^ Winkelmann, Juliane; Schormair, Barbara; Lichtner, Peter; Ripke, Stephan; Xiong, Lan; Jalilzadeh, Shapour; Fulda, Stephany; Pütz, Benno; Eckstein, Gertrud; Hauk, Stephanie; Trenkwalder, Claudia; Zimprich, Alexander; Stiasny-Kolster, Karin; Oertel, Wolfgang; Bachmann, Cornelius G; Paulus, Walter; Peglau, Ines; Eisensehr, Ilonka; Montplaisir, Jacques; Turecki, Gustavo; Rouleau, Guy; Gieger, Christian; Illig, Thomas; Wichmann, H-Erich; Holsboer, Florian; Müller-Myhsok, Bertram; Meitinger, Thomas (2007). "Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions". Nature Genetics. 39 (8): 1000–6. doi:10.1038/ng2099. PMID 17637780. S2CID 10606410.
  54. ^ Ding, Li; Getz, Gad; Wheeler, David A.; Mardis, Elaine R.; McLellan, Michael D.; Cibulskis, Kristian; Sougnez, Carrie; Greulich, Heidi; Muzny, Donna M.; Morgan, Margaret B.; Fulton, Lucinda; Fulton, Robert S.; Zhang, Qunyuan; Wendl, Michael C.; Lawrence, Michael S.; Larson, David E.; Chen, Ken; Dooling, David J.; Sabo, Aniko; Hawes, Alicia C.; Shen, Hua; Jhangiani, Shalini N.; Lewis, Lora R.; Hall, Otis; Zhu, Yiming; Mathew, Tittu; Ren, Yanru; Yao, Jiqiang; Scherer, Steven E.; Clerc, Kerstin (2008). "Somatic mutations affect key pathways in lung adenocarcinoma". Nature. 455 (7216): 1069–75. Bibcode:2008Natur.455.1069D. doi:10.1038/nature07423. PMC 2694412. PMID 18948947.
  55. ^ Stefansson, Hreinn; Rye, David B.; Hicks, Andrew; Petursson, Hjorvar; Ingason, Andres; Thorgeirsson, Thorgeir E.; Palsson, Stefan; Sigmundsson, Thordur; Sigurdsson, Albert P.; Eiriksdottir, Ingibjorg; Soebech, Emilia; Bliwise, Donald; Beck, Joseph M.; Rosen, Ami; Waddy, Salina; Trotti, Lynn M.; Iranzo, Alex; Thambisetty, Madhav; Hardarson, Gudmundur A.; Kristjansson, Kristleifur; Gudmundsson, Larus J.; Thorsteinsdottir, Unnur; Kong, Augustine; Gulcher, Jeffrey R.; Gudbjartsson, Daniel; Stefansson, Kari (16 August 2007). "A Genetic Risk Factor for Periodic Limb Movements in Sleep". New England Journal of Medicine. 357 (7): 639–647. doi:10.1056/NEJMoa072743. PMID 17634447. S2CID 44726156.
  56. ^ a b Moore, H; Winkelmann, J; Lin, L; Finn, L; Peppard, P; Mignot, E (2014). "Periodic leg movements during sleep are associated with polymorphisms in BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD". Sleep. 37 (9): 1535–1542. doi:10.5665/sleep.4006. PMC 4153066. PMID 25142570.
  57. ^ Allen, Richard (July 2004). "Dopamine and iron in the pathophysiology of restless legs syndrome (RLS)". Sleep Medicine. 5 (4): 385–391. doi:10.1016/j.sleep.2004.01.012. PMID 15222997.
  58. ^ Clemens, S.; Rye, D.; Hochman, S. (11 July 2006). "Restless legs syndrome: Revisiting the dopamine hypothesis from the spinal cord perspective". Neurology. 67 (1): 125–130. doi:10.1212/01.wnl.0000223316.53428.c9. PMID 16832090. S2CID 40963114.
  59. ^ Barrière, G.; Cazalets, J.R.; Bioulac, B.; Tison, F.; Ghorayeb, I. (October 2005). "The restless legs syndrome". Progress in Neurobiology. 77 (3): 139–165. doi:10.1016/j.pneurobio.2005.10.007. PMID 16300874. S2CID 9327680.
  60. ^ Dauvilliers, Yves; Winkelmann, Juliane (November 2013). "Restless legs syndrome: update on pathogenesis". Current Opinion in Pulmonary Medicine. 19 (6): 594–600. doi:10.1097/MCP.0b013e328365ab07. PMID 24048084. S2CID 20370566.
  61. ^ Klein, Marianne O.; Battagello, Daniella S.; Cardoso, Ariel R.; Hauser, David N.; Bittencourt, Jackson C.; Correa, Ricardo G. (January 2019). "Dopamine: Functions, Signaling, and Association with Neurological Diseases". Cellular and Molecular Neurobiology. 39 (1): 31–59. doi:10.1007/s10571-018-0632-3. PMID 30446950. S2CID 53567202.
  62. ^ Garcia-Borreguero, Diego; Williams, Anne-Marie (August 2014). "An update on restless legs syndrome (Willis-Ekbom disease): clinical features, pathogenesis and treatment". Current Opinion in Neurology. 27 (4): 493–501. doi:10.1097/WCO.0000000000000117. PMID 24978636.
  63. ^ Paulus, Walter; Trenkwalder, Claudia (October 2006). "Less is more: pathophysiology of dopaminergic-therapy-related augmentation in restless legs syndrome". The Lancet Neurology. 5 (10): 878–886. doi:10.1016/S1474-4422(06)70576-2. PMID 16987735. S2CID 43111931.
  64. ^ Allen, Richard P.; Montplaisir, Jacques; Walters, Arthur Scott; Ferini-Strambi, Luigi; Högl, Birgit (2017), "Restless Legs Syndrome and Periodic Limb Movements During Sleep", Principles and Practice of Sleep Medicine, Elsevier, pp. 923–934.e6, doi:10.1016/b978-0-323-24288-2.00095-7, ISBN 9780323242882
  65. ^ a b Sateia, Michael J (November 2014). "International Classification of Sleep Disorders-Third Edition". Chest. 146 (5): 1387–1394. doi:10.1378/chest.14-0970. PMID 25367475.
  66. ^ a b Breen, DP; Högl, B; Fasano, A; Trenkwalder, C; Lang, AE (July 2018). "Sleep-related motor and behavioral disorders: Recent advances and new entities". Movement Disorders. 33 (7): 1042–1055. doi:10.1002/mds.27375. PMID 29756278. S2CID 21672153.
  67. ^ "Restless legs syndrome—Treatment". National Health Service. 6 August 2018. Archived from the original on 15 May 2019. Retrieved 17 March 2019.
  68. ^ "Restless Legs Syndrome | Baylor Medicine". www.bcm.edu. Archived from the original on 2023-11-05. Retrieved 2023-11-06.
  69. ^ a b Allen, Richard P.; Earley, Christopher J. (2001). "Restless Legs Syndrome". Journal of Clinical Neurophysiology. 18 (2): 128–47. doi:10.1097/00004691-200103000-00004. PMID 11435804. S2CID 34082653.
  70. ^ Pacheco, Danielle; Wright, Heather (2023-05-05). "Treatment for Restless Legs Syndrome (RLS)". Sleep Foundation. Archived from the original on 2023-06-06. Retrieved 2023-06-18.
  71. ^ Foy, Jonette. "Regulation Name: Vibratory counter-stimulation device" (PDF). Food and Drug Administration. Archived (PDF) from the original on 24 October 2014. Retrieved 17 October 2014.
  72. ^ Trotti, Lynn M; Becker, Lorne A (4 January 2019). "Iron for the treatment of restless legs syndrome". Cochrane Database of Systematic Reviews (Systematic review). 2019 (1): CD007834. doi:10.1002/14651858.CD007834.pub3. PMC 6353229. PMID 30609006.
  73. ^ Zintzaras, Elias; Kitsios, Georgios D.; Papathanasiou, Afroditi A.; Konitsiotis, Spiros; Miligkos, Michael; Rodopoulou, Paraskevi; Hadjigeorgiou, George M. (February 2010). "Randomized trials of dopamine agonists in restless legs syndrome: A systematic review, quality assessment, and meta-analysis". Clinical Therapeutics. 32 (2): 221–237. doi:10.1016/j.clinthera.2010.01.028. PMID 20206780.
  74. ^ Winkelman, John W.; Armstrong, Melissa J.; Allen, Richard P.; Chaudhuri, K. Ray; Ondo, William; Trenkwalder, Claudia; Zee, Phyllis C.; Gronseth, Gary S.; Gloss, David; Zesiewicz, Theresa (13 December 2016). "Practice guideline summary: Treatment of restless legs syndrome in adults: Table: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology". Neurology. 87 (24): 2585–2593. doi:10.1212/wnl.0000000000003388. PMC 5206998. PMID 27856776.
  75. ^ Scholz, Hanna; Trenkwalder, Claudia; Kohnen, Ralf; Kriston, Levente; Riemann, Dieter; Hornyak, Magdolna (15 March 2011). "Dopamine agonists for the treatment of restless legs syndrome". Cochrane Database of Systematic Reviews. 2011 (5): CD006009. doi:10.1002/14651858.CD006009.pub2. PMC 8908466. PMID 21412893.
  76. ^ Scholz, Hanna; Trenkwalder, Claudia; Kohnen, Ralf; Kriston, Levente; Riemann, Dieter; Hornyak, Magdolna (15 February 2011). "Levodopa for the treatment of restless legs syndrome". Cochrane Database of Systematic Reviews. 2011 (5): CD005504. doi:10.1002/14651858.CD005504.pub2. PMC 8889887. PMID 21328278. S2CID 196338172.
  77. ^ Zanettini, Renzo; Antonini, Angelo; Gatto, Gemma; Gentile, Rosa; Tesei, Silvana; Pezzoli, Gianni (4 January 2007). "Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson's Disease". New England Journal of Medicine. 356 (1): 39–46. doi:10.1056/NEJMoa054830. PMID 17202454.
  78. ^ a b Mackie, Susan; Winkelman, John W. (May 2015). "Long-Term Treatment of Restless Legs Syndrome (RLS): An Approach to Management of Worsening Symptoms, Loss of Efficacy, and Augmentation". CNS Drugs. 29 (5): 351–357. doi:10.1007/s40263-015-0250-2. PMID 26045290.
  79. ^ Quilici, S.; Abrams, K.R.; Nicolas, A.; Martin, M.; Petit, C.; LLeu, P.-L.; Finnern, H.W. (October 2008). "Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome". Sleep Medicine. 9 (7): 715–726. doi:10.1016/j.sleep.2007.11.020. PMID 18226947.
  80. ^ Tippmann-Peikert, M.; Park, J. G.; Boeve, B. F.; Shepard, J. W.; Silber, M. H. (2007). "Pathologic gambling in patients with restless legs syndrome treated with dopaminergic agonists". Neurology. 68 (4): 301–3. doi:10.1212/01.wnl.0000252368.25106.b6. PMID 17242339. S2CID 26183000.
  81. ^ a b Aurora, R. Nisha; Kristo, David A.; Bista, Sabin R.; Rowley, James A.; Zak, Rochelle S.; Casey, Kenneth R.; Lamm, Carin I.; Tracy, Sharon L.; Rosenberg, Richard S. (August 2012). "The Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder in Adults—An Update for 2012: Practice Parameters with an Evidence-Based Systematic Review and Meta-Analyses". Sleep. 35 (8): 1039–1062. doi:10.5665/sleep.1988. PMC 3397811. PMID 22851801.
  82. ^ a b Zhou X, Du J, Liang Y, Dai C, Zhao L, Liu X, Tan C, Mo L, Chen L (2021). "The Efficacy and Safety of Pharmacological Treatments for Restless Legs Syndrome: Systemic Review and Network Meta-Analysis". Front Neurosci. 15: 751643. doi:10.3389/fnins.2021.751643. PMC 8576256. PMID 34764852.
  83. ^ a b Wanner V, Garcia Malo C, Romero S, Cano-Pumarega I, García-Borreguero D (2019). "Non-dopaminergic vs. dopaminergic treatment options in restless legs syndrome". Pharmacology of Restless Legs Syndrome (RLS). Adv Pharmacol. Vol. 84. pp. 187–205. doi:10.1016/bs.apha.2019.02.003. ISBN 9780128167588. PMID 31229171. S2CID 88409441.
  84. ^ a b c Riccardi S, Ferri R, Garbazza C, Miano S, Manconi M (April 2023). "Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis". J Clin Sleep Med. 19 (4): 811–822. doi:10.5664/jcsm.10440. PMC 10071388. PMID 36692194.
  85. ^ Iftikhar IH, Alghothani L, Trotti LM (December 2017). "Gabapentin enacarbil, pregabalin and rotigotine are equally effective in restless legs syndrome: a comparative meta-analysis". Eur J Neurol. 24 (12): 1446–1456. doi:10.1111/ene.13449. PMID 28888061. S2CID 22262972.
  86. ^ Winkelman JW, Armstrong MJ, Allen RP, Chaudhuri KR, Ondo W, Trenkwalder C, Zee PC, Gronseth GS, Gloss D, Zesiewicz T (December 2016). "Practice guideline summary: Treatment of restless legs syndrome in adults: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology". Neurology. 87 (24): 2585–2593. doi:10.1212/WNL.0000000000003388. PMC 5206998. PMID 27856776.
  87. ^ a b Silber MH, Becker PM, Buchfuhrer MJ, Earley CJ, Ondo WG, Walters AS, Winkelman JW (January 2018). "The Appropriate Use of Opioids in the Treatment of Refractory Restless Legs Syndrome". Mayo Clin Proc. 93 (1): 59–67. doi:10.1016/j.mayocp.2017.11.007. PMID 29304922. S2CID 12192080.
  88. ^ de Oliveira CO; Carvalho LB; Carlos K; Conti C; de Oliveira MM; Prado LB; Prado GF (29 June 2016). "Opioids for restless legs syndrome". Cochrane Database of Systematic Reviews. 6 (6): CD006941. doi:10.1002/14651858.CD006941.pub2. PMC 6885031. PMID 27355187.
  89. ^ Trenkwalder, Claudia; Winkelmann, Juliane; Inoue, Yuichi; Paulus, Walter (August 2015). "Restless legs syndrome—current therapies and management of augmentation". Nature Reviews Neurology. 11 (8): 434–445. doi:10.1038/nrneurol.2015.122. PMID 26215616. S2CID 22534190.
  90. ^ a b Carlos K, Prado GF, Teixeira CD, Conti C, de Oliveira MM, Prado LB, Carvalho LB (2017). "Benzodiazepines for restless legs syndrome". Cochrane Database Syst Rev. 2017 (3): CD006939. doi:10.1002/14651858.CD006939.pub2. PMC 6464545. PMID 28319266.
  91. ^ Garcia-Borreguero, Diego; Stillman, Paul; Benes, Heike; Buschmann, Heiner; Chaudhuri, K Ray; Gonzalez Rodríguez, Victor M; Högl, Birgit; Kohnen, Ralf; Monti, Giorgio Carlo; Stiasny-Kolster, Karin; Trenkwalder, Claudia; Williams, Anne-Marie; Zucconi, Marco (December 2011). "Algorithms for the diagnosis and treatment of restless legs syndrome in primary care". BMC Neurology. 11 (1): 28. doi:10.1186/1471-2377-11-28. PMC 3056753. PMID 21352569.
  92. ^ a b c Fulda S, Wetter TC (April 2008). "Where dopamine meets opioids: a meta-analysis of the placebo effect in restless legs syndrome treatment studies". Brain. 131 (Pt 4): 902–17. doi:10.1093/brain/awm244. PMID 17932100.
  93. ^ "HIGHLIGHTS OF PRESCRIBING INFORMATION" (PDF). www.accessdata.fda.gov. Archived (PDF) from the original on 5 November 2023. Retrieved 14 November 2023. -INDICATIONS AND USAGE- MIRAPEX is a non-ergot dopamine agonist indicated for the treatment of: • Parkinson's disease (PD) • Moderate-to-severe primary Restless Legs Syndrome (RLS)
  94. ^ "HIGHLIGHTS OF PRESCRIBING INFORMATION" (PDF). www.accessdata.fda.gov. Archived (PDF) from the original on 5 November 2023. Retrieved 14 November 2023. INDICATIONS AND USAGE -HORIZANT is indicated for: • treatment of moderate-to-severe primary Restless Legs Syndrome (RLS) in adults. • management of postherpetic neuralgia (PHN) in adults
  95. ^ a b c d e "Restless Legs Syndrome Factsheet". National Institutes of Health. Archived from the original on January 4, 2015. Retrieved January 13, 2015.
  96. ^ a b c d e Gamaldo, C. E.; Earley, C. J. (2006). "Restless Legs Syndrome: A Clinical Update". Chest. 130 (5): 1596–604. doi:10.1378/chest.130.5.1596. PMID 17099042.
  97. ^ Allen, R. P.; Walters, AS; Montplaisir, J; Hening, W; Myers, A; Bell, TJ; Ferini-Strambi, L (2005). "Restless Legs Syndrome Prevalence and Impact: REST General Population Study". Archives of Internal Medicine. 165 (11): 1286–92. doi:10.1001/archinte.165.11.1286. PMID 15956009.
  98. ^ Berger, K.; Luedemann, J; Trenkwalder, C; John, U; Kessler, C (2004). "Sex and the Risk of Restless Legs Syndrome in the General Population". Archives of Internal Medicine. 164 (2): 196–202. doi:10.1001/archinte.164.2.196. PMID 14744844.
  99. ^ "Welcome – National Sleep Foundation". Archived from the original on 2007-07-28. Retrieved 2007-07-23.
  100. ^ Lee, Kathryn A.; Zaffke, Mary Ellen; Baratte-Beebe, Kathleen (2001). "Restless Legs Syndrome and Sleep Disturbance during Pregnancy: The Role of Folate and Iron". Journal of Women's Health & Gender-Based Medicine. 10 (4): 335–41. doi:10.1089/152460901750269652. PMID 11445024.
  101. ^ Trenkwalder, C; Allen, R; Högl, B; Paulus, W; Winkelmann, J (5 April 2016). "Restless legs syndrome associated with major diseases: A systematic review and new concept". Neurology. 86 (14): 1336–1343. doi:10.1212/WNL.0000000000002542. PMC 4826337. PMID 26944272.
  102. ^ "Sleeping By Trimesters: 3rd Trimester". National Sleep Foundation. Archived from the original on 2007-05-08.
  103. ^ Yeh, Paul; Walters, Arthur S.; Tsuang, John W. (December 2012). "Restless legs syndrome: a comprehensive overview on its epidemiology, risk factors, and treatment". Sleep and Breathing. 16 (4): 987–1007. doi:10.1007/s11325-011-0606-x. PMID 22038683. S2CID 24079411.
  104. ^ Hening, Wayne; Allen, Richard; Earley, Christopher; Kushida, Clete; Picchietti, Daniel; Silber, Michael (1999). "The Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder". Sleep. doi:10.1093/sleep/22.7.970.
  105. ^ Schormair, Barbara (November 2017). "Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis". The Lancet Neurology. 16 (11): 898–907. doi:10.1016/S1474-4422(17)30327-7. PMC 5755468. PMID 29029846.
  106. ^ "Willis–Ekbom Disease Foundation Reverts to Original Name" (PDF). 2013. Archived from the original (PDF) on 2015-09-24.
  107. ^ Wittmaack–Ekbom syndrome at Who Named It?
  108. ^ Woloshin, Steven; Schwartz, Lisa M. (2006). "Giving Legs to Restless Legs: A Case Study of How the Media Helps Make People Sick". PLOS Medicine. 3 (4): e170. doi:10.1371/journal.pmed.0030170. PMC 1434499. PMID 16597175.
  109. ^ Templeton, Sarah-Kate (August 6, 2006). "Glaxo's cure for 'restless legs' was an unlicensed drug". Times Online. Times Newspapers Ltd. Archived from the original on February 11, 2007. Retrieved 2009-07-24.
  110. ^ a b c Aurora, R. Nisha; Kristo, David A.; Bista, Sabin R.; Rowley, James A.; Zak, Rochelle S.; Casey, Kenneth R.; Lamm, Carin I.; Tracy, Sharon L.; Rosenberg, Richard S. (August 2012). "Update to the AASM Clinical Practice Guideline: "The Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder in Adults—An Update for 2012: Practice Parameters with an Evidence-Based Systematic Review and Meta-Analyses"". Sleep. 35 (8): 1037. doi:10.5665/sleep.1986. PMC 3397810. PMID 22851800.

External links

Wikimedia Commons has media related to Restless leg syndrome.
Look up restless legs syndrome in Wiktionary, the free dictionary.
Classification
Diseases of the nervous system, primarily CNS
Authority control databases: National
Categories