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Restless legs syndrome: a comprehensive overview on its epidemiology, risk factors, and treatment

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Abstract

Purposes

Restless legs syndrome (RLS) is underdiagnosed and poorly understood by clinicians and the general public alike; accordingly, a broad literature review with information most relevant to general practice is needed to help dispel misconceptions and improve level of care.

Methods

Specifically, this review comprehensively provides an epidemiological analysis of RLS and examines the risk factors and treatment options for RLS by compiling the findings of past RLS studies. These RLS studies were identified through a retrospective PubMed search. The epidemiological analysis was conducted by calculating a weighted mean average of all the relevant general population RLS prevalence studies, separated into geographical/racial categories.

Results

A comprehensive analysis of RLS epidemiological studies finds the prevalence rate of RLS to be 5–15% in the general population with 2.5% of adults having symptoms severe enough to require medical intervention. Some of the risk factors for RLS include female gender, pregnancy, low iron levels, lower socioeconomic status, poor health, elderly age, comorbidity with Parkinson’s disease, positive family history of RLS, and comorbidity with psychiatric disorders. A wide array of treatment options exist for RLS including pharmacological and nonpharmacologic interventions.

Conclusions

Clinicians’ understanding of RLS enigma has recently improved due to the increased intensity of RLS research over the past decade. This review summarizes the current findings in the RLS field as well as providing guidelines for future RLS-related research.

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References

  1. Högl B, Kiechl S, Willeit J, Saletu M, Frauscher B, Seppi K, Muller J, Rungger G, Gasperi A, Wenning G, Poewe W (2005) Restless legs syndrome: a community-based study of prevalence, severity, and risk factors. Neurology 64:1920–1924

    Article  PubMed  Google Scholar 

  2. Allen RP, Walters A, Montplaisir J, Hening W, Myers A, Bell TJ, Ferini-Strambi L (2005) Restless legs syndrome prevalence and impact: REST general population survey. Arch Int Med 165:1286–1292

    Article  Google Scholar 

  3. BaHamamm A, Al-Sharani K, Al-Zahrani S, Al-Shammari A, Al-Amri N, Sharif M (2011) The prevalence of restless legs syndrome in adult Saudis attending primary health care. Gen Hosp Psychiatry 33(2):102–106

    Article  Google Scholar 

  4. Hadjigeorgiou GM, Sefandis I, Dardiotis E, Aggellakis K, Sakkas GK, Xiromerisiou G, Konitsiotis S, Paterakis K, Poultsidi A, Tsimourtou V, Ralli S, Gourgoulianis K, Zintzaras E (2007) Low RLS prevalence and awareness in central Greece: an epidemiological survey. Eur J Neurology 14(11):1275–1280

    Article  CAS  Google Scholar 

  5. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J, Restless Legs Syndrome Diagnosis and 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 Institute of Health. Sleep Med 4:101–119

    Article  PubMed  Google Scholar 

  6. Benes H, Walters AS, Allen RP, Hening WA, Kohnen R (2007) Definition of restless legs syndrome, how to diagnose it, and how to differentiate it from RLS mimics. Move Dis 22(S18):S401–S408

    Google Scholar 

  7. Ohayon MM, O’Hara R, Vitiello MV (2011) Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Med Rev. doi:10.1016/j.smrv.2011.05.002

  8. Walters AS (1995) Toward a better definition of the restless legs syndrome. The International Restless Legs Syndrome Study Group. Mov Disord 10:634–642

    Article  PubMed  CAS  Google Scholar 

  9. Walters AS, Winkelmann J, Trenkwalder C, Fry JM, Kataria V, Wagner M, Sharma R, Hening W, Li L (2001) Long-term follow-up on restless legs syndrome patients treated with opioids. Mov Disord 16:1105–1109

    Article  PubMed  CAS  Google Scholar 

  10. Hanson M, Honour M, Singleton A, Crawley A, Singleton A, Hardy J, Gwinn-Hardy K (2004) Analysis of familial and sporadic restless legs syndrome in age of onset, gender, and severity features. J Neurol 251(11):1398–1401

    Article  PubMed  Google Scholar 

  11. Allen RP, La Buda MC, Becker P, Earley CJ (2002) Family history study of the restless legs syndrome. Sleep Med 3(Suppl):S3–S7

    Article  PubMed  Google Scholar 

  12. Dantas F, Medeiros J,Farias K, Ribeiro CD (2008) Restless legs syndrome in institutionalized elderly. Arquivos de Neuro-Psiquiatria 66(2b):328–330

    Google Scholar 

  13. Yee B, Killick R, Wang K (2009) Restless legs syndrome. Aust Fam Phys 38(5):296–300

    Google Scholar 

  14. Lang AE (1993) Akathisia and the restless legs syndrome. In: Jankovic E, Tolosa E (eds) Parkinson's disease and movement disorders, 2nd edn. Williams & Wilkins, Baltimore, pp 399–418

    Google Scholar 

  15. Hening WA, Allen RP, Thanner S, Washburn T, Heckler D, Walters AS, Earley CJ (2003) The Johns Hopkins telephone diagnostic interview for the restless legs syndrome: preliminary investigation for validation in a multi-center patient and control population. Sleep Med 4:137–141

    Article  PubMed  Google Scholar 

  16. Allen RP, Earley CJ (2001) Validation of the Johns Hopkins restless legs severity scale. Sleep Med 2:239–242

    Article  PubMed  Google Scholar 

  17. Kohnen R, Allen RP, Benes H, Garcia-Borreguero D, Hening WA, Stiasny-Kolster K, Zucconi M (2007) Assessment of restless legs syndrome—methodological approaches for use in practice and clinical trials. Mov Disord 22:S485–S494

    Article  PubMed  Google Scholar 

  18. Abetz L, Arbuckle R, Allen RP, Garcia-Borreguero D, Hening W, Walters AS, Mavraki E, Kirsch JM (2006) The reliability, validity and responsiveness of the International Restless Legs Syndrome Study Group rating scale and subscales in a clinical-trial setting. Sleep Med 7:340–349

    Article  PubMed  Google Scholar 

  19. Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C (2003) Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 4:121–132

    Article  PubMed  Google Scholar 

  20. Hening W, Walters AS, Allen AP, Montplaisir J, Myers A, Ferini-Strambi L (2004) Impact, diagnosis, and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med 5:3–237

    Article  Google Scholar 

  21. Cotter PE, O’Keeffe ST (2006) Restless leg syndrome: is it a real problem? Ther Clin Risk Manage 2(4):465–475

    Article  CAS  Google Scholar 

  22. Allen RP, Stillman P, Myers AJ (2010) Physician-diagnosed restless legs syndrome in a large sample of primary medical care patients in Western Europe: prevalence and characteristics. Sleep Med 11(1):31–37

    Article  PubMed  Google Scholar 

  23. Picchietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi L (2007) Restless legs syndrome: prevalence and impact in children and adolescents—the Peds REST study. Pediatrics 120(2):253–266

    Article  PubMed  Google Scholar 

  24. Hening WA, Allen RP, Chaudhuri KR, Hornyak M, Lee HB, Winkelman J, Yoakum R (2007) Clinical Significance of RLS. Move Dis 22(S18):S395–S400

    Google Scholar 

  25. Trenkwalder C, Allen R (2006) Epidemiology and social costs of restless legs syndrome (RLS). J Sleep Res 15(Supplement 1):9

    Google Scholar 

  26. Hening WA, Allen RP, Earley CJ, Picchietti DL, Silber MH (2004) An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep 27:560–583

    PubMed  Google Scholar 

  27. Molnar MZ, Novak M, Szeifert L, Ambrus C, Keszei A, Koczy A, Lindner A, Barotfi S, Szentkiralyi A, Remport A, Mucsi I (2007) Restless legs syndrome, insomnia, and quality of life after renal transplantation. J Psychosom Res 63(6):591–597

    Article  PubMed  Google Scholar 

  28. Abetz L, Vallow SM, Kirsch J, Allen RP, Washburn T, Earley CJ (2005) Validation of the Restless Legs Syndrome Quality of Life questionnaire. Value Health 8(2):157–167

    Article  PubMed  Google Scholar 

  29. Tan EK, Seah A, See SJ, Lim E, Wong MC, Koh KK (2001) Restless legs syndrome in an Asian population: a study in Singapore. Mov Disord 16(3):577–579

    Article  PubMed  CAS  Google Scholar 

  30. Lavigne GJ, Montplaisir JY (1994) RLS and sleep bruxism—prevalence and association among Canadians. Sleep 17(8):739–743

    PubMed  CAS  Google Scholar 

  31. Phillips B, Hening W, Britz P, Mannino D (2006) Prevalence and correlates of restless legs syndrome—results from the 2005 National Sleep Foundation Poll. Chest 129(1):76–80

    Article  PubMed  Google Scholar 

  32. Nichols DA, Allen RP, Grauke JH, Brown JB, Rice ML, Hyde PR, Dement WC, Kushida CA (2003) RLS in primary care: a prevalence study. Arch Intern Medicine 163(19):2323–2329

    Article  Google Scholar 

  33. Oboler SK, Prochazka AV, Meyer TJ (1991) Legs symptoms in outpatient veterans. West J Medicine 155:256–259

    CAS  Google Scholar 

  34. Berger K, Kurth T (2007) RLS Epidemiology—frequencies, risk factors and methods in population studies. Move Dis 22(Suppl.18):S420–S423

    Google Scholar 

  35. Winkler AS, Trendafilova A, Meindl M, Kaaya J, Schmutzhard E, Kassubek J (2010) Restless legs syndrome in a population of Northern Tanzania: a community-based study. Mov Disord 25(5):596–601

    Article  PubMed  Google Scholar 

  36. Nomura T, Inoue Y, Kusumi M, Oka Y, Nakashima K (2008) E-mail based epidemiological surveys on restless legs syndrome in Japan. Sleep Bio Rhythms 6(3):139–145

    Article  Google Scholar 

  37. Lee HB, Morgan JC (2007) Race, RLS, PLMs: an epidemic conundrum. Sleep Med 8(3):196–197

    Article  PubMed  Google Scholar 

  38. Eckeli AL, Gitai LLG, Dach F, Ceretta H, Sander HH, Passos ADC, do Prado GF, Fernandes RMF (2011) Prevalence of restless legs syndrome in the rural town of Cassia dos Coqueiros. Sleep Med. doi:10.1016/j.sleep.2011.01.018

  39. Turkdogan D, Bekiroglu N, Zaimoglu S (2011) A prevalence study of restless legs syndrome in Turkish children and adolescents. Sleep Med 12(4):315–321

    Article  PubMed  Google Scholar 

  40. Benediktsdottir B, Janson C, Lindberg E, Arnardóttir ES, Olafsson I, Cook E, Thorarinsdottir EH, Gislason T (2010) Prevalence of restless legs syndrome among adults in Iceland and Sweden: lung function, comorbidity, ferritin, biomarkers and quality of life. Sleep Med 11(10):1043–1048

    Article  PubMed  Google Scholar 

  41. Zeitlhofer J, Seidel S, Klösch G, Moser D, Anderer P, Saletu B, Bolitschek J, Popovic R, Lehofer M, Mallin W, Fugger B, Holzinger B, Kerbl R, Saletu A, Machatschke IH, Pavelka R, Högl B (2010) Sleep habits and sleep complaints in Austria: current self-reported data on sleep behaviour, sleep disturbances and their treatment. Acta Neurol Scand 122(6):389–403

    Article  Google Scholar 

  42. Chen NH, Chuang LP, Yang CT, Kushida CA, Hsu SC, Wang PC, Lin SW, Chou YT, Chen RS, Li HY, Lai SC (2010) The prevalence of restless legs syndrome in Taiwanese adults. Psychiatry Clin Neurosci 64(2):170–178

    Article  PubMed  Google Scholar 

  43. Tasdemir M, Erdogan H, Boru UT, Dilaver E, Kumaş A (2010) Epidemiology of restless legs syndrome in Turkish adults on the western Black Sea coast of Turkey: a door-to-door study in a rural area. Sleep Med 11(1):82–86

    Article  PubMed  Google Scholar 

  44. Moller C, Wetter TC, Köster J, Stiasny-Kolster K (2010) Differential diagnosis of unpleasant sensations in the legs: prevalence of restless legs syndrome in a primary care population. Sleep Med 11(2):161–166

    Article  PubMed  Google Scholar 

  45. Cho SJ, Hong JP, Hahm BJ, Jeon HJ, Chang SM, Cho MJ, Lee HB (2009) Restless legs syndrome in a community sample of Korean adults: prevalence, impact on quality of life, and association with DSM-IV psychiatric disorders. Sleep 32:1069–1079

    PubMed  Google Scholar 

  46. Nomura T, Inoue Y, Kusumi M, Uemura Y, Nakashima K (2009) Prevalence of restless legs syndrome in rural community in Japan. Mov Disord 23(16):2363–2369

    Article  Google Scholar 

  47. Froese CL, Butt A, Mulgrew A, Cheema R, Speirs MA, Gosnell C, Fleming J, Fleetham J, Ryan CF, Ayas NT (2008) Depression and sleep-related symptoms in an adult, indigenous, North American population. J Clin Sleep Med 4:356–361

    PubMed  Google Scholar 

  48. Cho YW, Shin WC, Yun CH, Hong SB, Kim JH, Allen RP, Earley CJ (2008) Epidemiology of restless legs syndrome in Korean adults. Sleep 31(2):219–223

    PubMed  Google Scholar 

  49. Happe S, Vennemann M, Evers S, Berger K (2008) Treatment wish of individuals with known and unknown restless legs syndrome in the community. J Neurology 255:1365–1371

    Article  Google Scholar 

  50. Broman JE, Mallon L, Hetta J (2008) Restless legs syndrome and its relationship with insomnia symptoms and daytime distress: epidemiological survey in Sweden. Psychiatry Clin Neurosci 62:472–475

    Article  PubMed  Google Scholar 

  51. Rangarajan S, Ragarahan S, D’Souza GA (2007) Restless legs syndrome in an Indian urban population. Sleep Med 9(1):88–93

    Article  PubMed  Google Scholar 

  52. Ulfberg J, Bjorvatn B, Leissner L, Gyring J, Karlsborg M, Regeur L, Skeidsvoll H, Polo O, Partinen M (2007) Comorbidity in restless legs syndrome among a sample of Swedish adults. Sleep Med 8(7–8):768–772

    Article  PubMed  Google Scholar 

  53. Vogl FD, Pichler I, Adel S, Pinggera GK, Bracco S, De Grandi A, Volpato CB, Aridon P, Mayer T, Meitinger T, Klein C, Casari G, Pramstaller PP (2006) Epidemiological and clinicogenetic study in a South Tyrolean population isolate. Mov Disord 21:1189–1195

    Article  PubMed  Google Scholar 

  54. Castillo PR, Kaplan J, Lin SC, Fredrickson PA, Mahowald MW (2006) Prevalence of restless legs syndrome among native South Americans residing in coastal and mountainous areas. Mayo Clin Proc 81(10):1345–1347

    Article  PubMed  Google Scholar 

  55. Kim J, Choi C, Shin K, Yi H, Park M, Cho N, Kimm K, Shin C (2005) Prevalence of restless legs syndrome and associated factors in the Korean adult population: The Korean Health and Genome Study. Psychiatry Clin Neurosci 59(3):350–353

    Article  PubMed  Google Scholar 

  56. Tison F, Crochard A, Léger D, Bouée S, Lainey E, El Hasnaoui A (2005) Epidemiology of restless legs syndrome in French adults: a nationwide survey: the INSTANT Study. Neurology 65:239–246

    Article  PubMed  CAS  Google Scholar 

  57. Bjorvatn B, Leissner L, Ulfberg J, Gyring J, Karlsborg M, Regeur L, Skeidsvoll H, Nordhus IH, Pallesen S (2005) Prevalence, severity and risk factors of restless legs syndrome in the general adult population in two Scandinavian countries. Sleep Med 6:307–312

    Article  PubMed  Google Scholar 

  58. Mizuno S, Miyaoka T, Inagaki T, Horiguchi J (2005) Prevalence of restless legs syndrome in non-institutionalized Japanese elderly. Psychiatry Clin Neurosci 59:461–465

    Article  PubMed  Google Scholar 

  59. Berger K, Luedemann J, Trenkwalder C, John U, Kessler C (2004) Sex and the risk of RLS in the general population. Arch Intern Medicine 164:196–202

    Article  Google Scholar 

  60. Rijsman R, Neven AK, Graffelman W, Kemp B, de Weerd A (2004) Epidemiology of restless legs in The Netherlands. Eur J Neurol 11(9):607–611

    Article  PubMed  Google Scholar 

  61. Sevim S, Dogu O, Camdeviren H, Bugdayci R, Sasmaz T, Kaleagasi H, Aral M, Helvaci I (2003) Unexpectedly low prevalence and unusual characteristics of RLS in Mersin, Turkey. Neurology 61(11):1562–1569

    Article  PubMed  CAS  Google Scholar 

  62. Ohayon MM, Roth T (2002) Prevalence of RLS and periodic limb movement disorder in the general population. J Psychosom Res 53(1):547–554

    Article  PubMed  Google Scholar 

  63. Ulfberg J, Nystrom B, Carter N, Edling C (2001) Restless legs syndrome among young men aged 18 to 64 years old: an association with somatic disease and neuropsychiatric disorder. Mov Disord 16(6):1159–1163

    Article  PubMed  CAS  Google Scholar 

  64. Ulfberg J, Nystrom B, Carter N, Edling C (2001) Restless legs syndrome among working-aged women. Eur Neurol 46(1):17–19

    Article  PubMed  CAS  Google Scholar 

  65. Diego G-B (2001) Restless legs syndrome: a clinical study in general Chilean population and in uremic patients (review). Sleep Med 2(6):557–559

    Article  Google Scholar 

  66. Kageyama T, Kabuto M, Nitta H, Kurokawa Y, Taira K, Suzuki S, Takemoto T (2000) Prevalence of periodic limb movement-like and restless legs syndrome-like symptoms among Japanese adults. Psychiatry Clin Neurosci 54(3):296–298

    Article  PubMed  CAS  Google Scholar 

  67. Schmitt BE, Gugger M, Augustiny K, Bassetti C, Radanov BP (2000) Prevalence of sleep complaints: a questionnaire-based study of a Swiss working population. Schweiz Med Wochenschr 130(21):772–778

    PubMed  CAS  Google Scholar 

  68. O’Hare JA, Abuaisha F, Geoghegan M (1994) Prevalence and forms of neuropathic morbidity in 800 diabetic patients. Ir J Med Sci 163(3):132–135

    Article  PubMed  Google Scholar 

  69. Strang RR (1967) The symptom of restless legs. Medicine J Aust 1:1211–1213

    CAS  Google Scholar 

  70. Ekbom KA (1945) Restless legs: a clinical study. Acta Med Scand 158:1–123

    Google Scholar 

  71. Allen RP, Bharmal M, Calloway M (2011) Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Mov Disord 26(1):114–120

    Article  PubMed  Google Scholar 

  72. Ram S, Seirawan H, Kumar SK, Clark GT (2010) Prevalence and impact of sleep disorders and sleep habits in the States. Sleep Breath 14(1):63–70

    Article  PubMed  Google Scholar 

  73. Winkelman JW, Redline S, Baldwin CM, Resnick HE, Newman AB, Gottlieb DJ (2009) Polysomnographic and health-related quality of life correlates of restless legs syndrome in the sleep heart health study. Sleep 32:772–778

    PubMed  Google Scholar 

  74. Winkelman JW, Shahar E, Sharief I, Gottlieb DJ (2008) Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study. Neurology 70:35–42

    Article  PubMed  Google Scholar 

  75. Lee HB, Hening WA, Allen RP, Earley CJ, Eaton WW, Lyketsos CG (2006) Race and restless legs syndrome symptoms in an adult community sample in east Baltimore. Sleep Med 7(8):642–645

    Article  PubMed  Google Scholar 

  76. Phillips B, Young T, Finn L, Asher K, Hening WA, Purvis C (2000) Epidemiology of restless legs syndrome in adults. Arch Intern Medicine 160(14):2137–2141

    Article  CAS  Google Scholar 

  77. Purvis C, Phillips B, Asher K (1997) Self report of RLS: 1996 Kentucky Behavior risk factor surveillance survey. J Sleep Res 26:474

    Google Scholar 

  78. Bentley AJ, Rosman KD, Mitchell D (2006) Gender differences in the presentation of subjects with restless legs syndrome. Sleep Med 7(1):37–41

    Article  PubMed  Google Scholar 

  79. Gijbers van Wijk CM, Huisman H, Kolk AM (1999) Gender differences in physical symptoms and illness behavior. A health diary study. Soc Sci Med 49(8):1061–1074

    Article  Google Scholar 

  80. Jahn I (2005) Taking into consideration gender and sex. New chances to improve the quality of epidemiological and health research. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 48(3):287–295

    Article  PubMed  CAS  Google Scholar 

  81. Garcia-Borreguero D, Egatz R, Winkelmann J, Berger K (2006) Epidemiology of restless legs syndrome: the current status. Sleep Med Rev 10(3):153–167

    Article  PubMed  Google Scholar 

  82. Ekbom K (1960) Restless legs syndrome. Neurology 10:868–873

    Article  PubMed  CAS  Google Scholar 

  83. Goodman JD, Brodie C, Ayida GA (1988) Restless legs syndrome in pregnancy. Br Medicine J 297(6656):1101–1102

    Article  CAS  Google Scholar 

  84. Manconi M, De Vito A, Economou NT, Cesnik E, Mollica G, Granieri E (2002) Pregnancy as a risk factor for restless legs syndrome. J Sleep Research 11:145

    Google Scholar 

  85. Suzuki K, Ohida T, Sone T, Takemura S, Yokoyama E, Miyake T, Harano S, Motojima S, Suga M, Ibuka E (2003) The prevalence of restless legs syndrome among pregnant women in Japan and the relationship between restless legs syndrome and sleep problems. Sleep 26(6):673–677

    PubMed  Google Scholar 

  86. Tunç T, Karadağ YS, Doğulu F, Inan LE (2009) Predisposing factors of restless legs syndrome in pregnancy. Mov Disord 22(5):627–631

    Article  Google Scholar 

  87. Alves DA, Carvalho LB, Morais JF, Prado GF (2010) Restless legs syndrome during pregnancy in Brazilian women. Sleep Med 11(10):1049–1054

    Article  PubMed  Google Scholar 

  88. Dzaja A, Wehrle R, Lancel M, Pollmächer T (2009) Elevated estradoil plasma levels in women with restless legs during pregnancy. Sleep 32(2):169–174

    PubMed  Google Scholar 

  89. Neau JP, Marion P, Mathis S, Julian A, Godeneche G, Larrieu D, Meurice JC, Paquereau J, Ingrand P (2010) Restless legs syndrome and pregnancy: follow-up of pregnant women before and after delivery. Eur Neurol 64(6):361–366

    Article  PubMed  Google Scholar 

  90. Harano S, Hida T, Kaneita Y, Yokoyama E, Tamaki T, Takemura S, Osaki Y, Hayashi K (2008) Prevalence of restless legs syndrome with pregnancy and relationship with sleep disorders in the Japanese large population. Sleep and Biological Rhythms 6(2):102–109

    Article  Google Scholar 

  91. Manconi M, Govoni V, De Vito A, Economou NT, Cesnik E, Casetta I, Mollica G, Ferini-Strambi L, Granieri E (2004) Restless legs syndrome and pregnancy. Neurology 63(6):1065–1069

    Article  PubMed  CAS  Google Scholar 

  92. Ismailogullari S, Ozturk A, Mazicioglu MM, Serin S, Gultekin M, Aksu M (2010) Restless legs syndrome and pregnancy in Kayseri, Turkey: a hospital based survey. Sleep and Biological Rhythms 8(2):137–143

    Article  Google Scholar 

  93. Wesstrom J, Nilsson S, Sundstrom-Poromaa I, Ulfberg J (2008) Restless legs syndrome among women: prevalence, co-morbidity and possible relationship to menopause. Climacteric 11(5):422–428

    Article  PubMed  CAS  Google Scholar 

  94. Lee KA, Zaffke ME, Baratte-Beebe K (2001) Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron. J Womens Health Gend Based Medicine 10(4):335–341

    Article  CAS  Google Scholar 

  95. Jolivet B (1953) Paresthésies agitantes nocturnes des membres inférieurs, impatiences, Thése de Paris

  96. Guyatt GH, Patterson C, Ali M, Singer J, Levine M, Turpie I, Meyer R (1990) Diagnosis of iron-deficiency anaemia in the elderly. Am J Medicine 88:205–209

    Article  CAS  Google Scholar 

  97. Allen RP, Hening WA, Earley CJ (2008) Adult RLS patients show lower serum ferritin occurs with earlier age-of-onset of RLS symptoms indicating RLS may impair the normal age-related increase in brain iron. Sleep 31(S.814):A267

    Google Scholar 

  98. Allen RP, Barker PB, Wehrl F, Song HK, Earley CJ (2001) MRI measurement of brain iron in patients with restless legs syndrome. Neurology 56(2):263–265

    Article  PubMed  CAS  Google Scholar 

  99. Reynolds G, Blake DR, Pall HS, Williams A (1986) Restless legs syndrome and rheumatoid arthritis. Br Med J 292(6521):659–660

    Article  CAS  Google Scholar 

  100. Ondo W, Tan EK, Mansoor J (2000) Rheumatologic serologies in secondary restless legs syndrome. Mov Disord 15(2):321–323

    Article  PubMed  CAS  Google Scholar 

  101. Rangarajan S, D’souza GA, Srikanth AM (2007) Restless legs syndrome in Indian patients having iron deficiency anemia in a tertiary care hospital. Sleep 8(3):247–251

    Article  Google Scholar 

  102. Ulfberg J, Nystrom B (2004) Restless legs syndrome in blood donors. Sleep Med 5(2):115–118

    Article  PubMed  Google Scholar 

  103. O’Keeffe ST, Gavin K, Lavan JN (1994) Iron status and restless legs syndrome in the elderly. Age Ageing 23(3):200–203

    Article  PubMed  Google Scholar 

  104. Sun ER, Chen CA, Ho G, Earley CJ, Allen RP (1998) Iron and the restless legs syndrome. Sleep 21(4):371–377

    PubMed  CAS  Google Scholar 

  105. Frauscher B, Gschliesser V, Brandauer E, El-Demerdash E, Kaneider M, Rücker L, Poewe W, Högl B (2009) The severity range of restless legs syndrome (RLS) and augmentation in a prospective patient cohort: Association with ferritin levels. Sleep Med 10(6):611–615

    Article  PubMed  Google Scholar 

  106. Cançado RD, Chiattone CS, Alonso FF, Langhi Júnior DM, Alves Rde C (2001) Iron deficiency in blood donors. Sao Paulo Medicine J 119:132–134

    Google Scholar 

  107. Minai OA, Golish JA, Yataco JC, Budev MM, Blazey H, Giannini C (2007) Restless legs syndrome in lung transplant recipients. J Heart Lung Transplant 26(1):24–29

    Article  PubMed  Google Scholar 

  108. Kawauchi A, Inoue Y, Hashimoto T, Tachibana N, Shirakawa S, Mizutani Y, Ono T, Miki T (2006) Restless legs syndrome in hemodialysis patients: health-realted quality of life and laboratory data analysis. Clin Nephrol 66(6):440–446

    PubMed  CAS  Google Scholar 

  109. Takaki J, Nishi T, Nangaku M, Shimoyama H, Inada T, Matsuyama N, Kumano H, Kuboki T (2003) Clinical and psychological aspects of restless legs syndrome in uremic patients on hemodialysis. American Journey of Kidney Diseases 41(4):833–839

    Article  Google Scholar 

  110. Sakkas GK, Hadjigeorgiou GM, Karatzaferi C, Maridaki MD, Giannaki CD, Mertens PR, Rountas C, Vlychou M, Liakopoulos V, Stefanidis I (2008) Intradialytics aerobic exercise training ameliorates symptoms of restless legs syndrome and improves functional capacity in patients on hemodialysis: a pilot study. ASAIO J 54(2):185–190

    Article  PubMed  Google Scholar 

  111. Aukerman MM, Aukerman D, Bayard M, Tudiver F, Thorp L, Bailey B (2006) Exercise and restless legs syndrome: a randomized controlled trial. J Am Board Fam Medicine 19(5):487–493

    Article  Google Scholar 

  112. Gao X, Schwarzschild MA, Wang H, Ascherio A (2009) Obesity and restless legs syndrome in men and women. Neurology 72(14):1255–1261

    Article  PubMed  Google Scholar 

  113. Minai OA, Mailk N, Foldvary N, Bair N, Golish JA (2008) Prevalence and characteristics of restless legs syndrome in patients with pulmonary hypertension. J Heart Lung Transplant 27(3):335–340

    Article  PubMed  Google Scholar 

  114. Winkelman JW, Finn L, Young T (2006) Prevalence and correlates of restless legs syndrome symptoms in the Wisconsin Sleep Cohort. Sleep Med 7(7):545–552

    Article  PubMed  Google Scholar 

  115. Schlesinger I, Erikh I, Avizohar O, Sprecher E, Yarnitsky D (2009) Cardiovascular risk factors in restless legs syndrome. Mov Disord 24(11):1587–1592

    Article  PubMed  Google Scholar 

  116. Manconi M, Ferini-Strambi L, Filippi M, Bonanni E, Iudice A, Murri L, Gigli GL, Fratticci L, Merlino G, Terzano G, Granella F, Parrino L, Silvestri R, Aricò I, Dattola V, Russo G, Luongo C, Cicolin A, Tribolo A, Cavalla P, Savarese M, Trojano M, Ottaviano S, Cirignotta F, Simioni V, Salvi F, Mondino F, Perla F, Chinaglia G, Zuliani C, Cesnik E, Granieri E, Placidi F, Palmieri MG, Manni R, Terzaghi M, Bergamaschi R, Rocchi R, Ulivelli M, Bartalini S, Ferri R, Lo Fermo S, Ubiali E, Viscardi M, Rottoli M, Nobili L, Protti A, Ferrillo F, Allena M, Mancardi G, Guarnieri B, Londrillo F (2008) Multicenter case-control study on restless legs syndrome in multiple sclerosis: the MEMO study. Sleep 31(7):944–952

    PubMed  Google Scholar 

  117. Chen WC, Lim PS, Wu WC, Chiu HC, Chen CH, Kuo HY, Tsai TW, Chien PI, Su YJ, Su YL, Hung SH, Woods HF (2006) Sleep behavior disorders in a large cohort of Chinese (Taiwanese) patients maintained by long-term hemodialysis. Am J Kidney Dis 48:277–284

    Article  PubMed  Google Scholar 

  118. Gigli GL, Adorati M, Dolso P, Piani A, Valente M, Brotini S, Budai R (2004) Restless legs syndrome in end-stage renal disease. Sleep Med 5(3):309–315

    Article  PubMed  Google Scholar 

  119. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS (2001) Brain dopamine and obesity. Lancet 357:354–357

    Article  PubMed  CAS  Google Scholar 

  120. Auger C, Montplaisir J, Duquette P (2005) Increased frequency of restlesslegs syndrome in a French–Canadian population with multiple sclerosis. Neurology 65:1652–1653

    Article  PubMed  Google Scholar 

  121. Moreira NCV, Damasceno RS, Medeiros CAM, Bruin PF, Teixeira CA, Horta WG, Bruin VM (2008) Restless legs syndrome, sleep quality and fatigue in multiple sclerosis patients. Braz J Med Biol Res 41(10):932–937

    Article  PubMed  CAS  Google Scholar 

  122. van Eeghen AM, Numis AI, Staley BA, Therrien SE, Thibert RL, Thiele EA (2011) Characterizing sleep disorders of adults with tuberous sclerosis complex: a questionnaire-based study and review. Epilepsy Behav 20(1):68–74

    Article  PubMed  Google Scholar 

  123. Weinstock LB, Walters AS, Mullin GE, Duntley SP (2010) Celiac disease is associated with restless legs syndrome. Dig Dis Sci 55(6):1667–1673

    Article  PubMed  Google Scholar 

  124. Moccia M, Pellecchia MT, Erro R, Zingone F, Marelli S, Barone DG, Ciacci C, Strambi LF, Barone P (2010) Restless legs syndrome is a common feature of adult celiac disease. Mov Disord 25(7):877–881

    Article  PubMed  Google Scholar 

  125. Lopes LA, Lins Cde M, Adeodato VG, Quental DP, de Bruin PF, Montenegro RM Jr, de Bruin VM (2005) Restless legs syndrome and quality of sleep in type 2 diabetes. Diabetes Care 28(11):2633–2636

    Article  PubMed  Google Scholar 

  126. Greco D, Gambina F, Pisciotta M, Abrignani M, Maggio F (2009) Clinical characteristics and associated comorbidities in diabetic patients with restless legs syndrome. Exp Clin Endocrinol Diabetes 117(9):496–499

    Article  PubMed  CAS  Google Scholar 

  127. Viola-Saltzman M, Watson NF, Bogart A, Goldberg J, Buchwald D (2010) High prevalence of restless legs syndrome among patients with fibromyalgia: a controlled cross-sectional study. J Clin Sleep Med 6(5):423–427

    PubMed  Google Scholar 

  128. Taylor-Gjevre RM, Gjevre JA, Nair B, Skomro R, Lim HJ (2010) Hypersomnolence and sleep disorders in a rheumatic disease patient population. J Clin Rheumatol 16(6):255–261

    Article  PubMed  Google Scholar 

  129. Rajabally YA, Shah RS (2010) Restless legs syndrome in chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 42(2):252–256

    Article  PubMed  Google Scholar 

  130. Boentert M, Dziewas R, Heidbreder A, Happe S, Kleffner I, Evers S, Young P (2010) Fatigue, reduced sleep quality and restless legs syndrome in Charcot–Marie–Tooth disease: a web-based survey. J Neurol 257(4):646–652

    Article  PubMed  Google Scholar 

  131. Weinstock LB, Bosworth BP, Scherl EJ, Li E, Iroku U, Munsell MA, Mullen GE, Walters AS (2010) Crohn's disease is associated with restless legs syndrome. Inflamm Bowel Dis 16(2):275–279

    PubMed  Google Scholar 

  132. Lespérance P, Djerroud N, Diaz Anzaldua A, Rouleau GA, Chouinard S, Richer F (2004) Restless legs in Tourette syndrome. Mov Disord 19(9):1084–1087

    Article  PubMed  Google Scholar 

  133. Rutkove SB, Matheson JK, Logigian EL (1996) Restless legs syndrome in patients with polyneuropathy. Muscle Nerve 19(5):670–672

    Article  PubMed  CAS  Google Scholar 

  134. De Mello MT, Laura FAA, Silva AC, Tufik S (1996) Incidence of periodic leg movements and of the restless legs syndrome during sleep following acute physical activity in spinal cord injury subjects. Spinal Cord 34(5):294–296

    Article  PubMed  Google Scholar 

  135. Telles SCL, Alves RC, Chadi G (2011) Periodic limb movements during sleep and restless legs syndrome in patients with ASIA A spinal cord injury. J Neurol Sci 303(1–2):119–123

    Article  PubMed  Google Scholar 

  136. Plazzi G, Ferri R, Antelmi E, Bayard S, Franceschini C, Cosentino FI, Abril B, Spruyt K, Provini F, Montagna P, Dauvilliers Y (2010) Restless legs syndrome is frequent in narcolepsy with cataplexy patients. Sleep 33(5):689–694

    PubMed  Google Scholar 

  137. Plazzi G, Ferri R, Franceschini C, Vandi S, Detto S, Pizza F, Poli F, De Cock VC, Bayard S, Dauvilliers Y (2011) Periodic leg movements during sleep in narcoleptic patients with or without restless legs syndrome. J Sleep Res. doi:10.1111/j.1365-2869.2011.00942.x

  138. Caylak E (2009) The genetics of sleep disorders in humans: narcolepsy, restless legs syndrome, and obstructive sleep apnea syndrome. Am J Med Genet A 149A:2612–2626

    Article  PubMed  CAS  Google Scholar 

  139. Gamaldo CE, Benbrook AR, Allen RP, Scott JA, Henning WA, Earley CJ (2007) Childhood and adult factors associated with restless legs syndrome (RLS) diagnosis. Sleep Med 8(7–8):716–722

    Article  PubMed  Google Scholar 

  140. Spiegelhalder K, Hornyak M (2008) Restless legs syndrome in older adults. Clin Geriat Med 24(1):167–180

    Article  Google Scholar 

  141. Rothdach AJ, Trenkwalder C, Haberstock J, Keil U, Berger K (2000) Prevalence and risk factors of RLS in an elderly population—the Memo study. Neurology 54(5):1064–1068

    Article  PubMed  CAS  Google Scholar 

  142. Celle S, Roche F, Kerleroux J, Thomas-Anterion C, Laurent B, Rouch I, Pichot V, Barthélémy JC, Sforza E (2010) Prevalence and clinical correlates of restless legs syndrome in an elderly French population: the Synapse study. J Ger Series A Bio Sci Med Sci 65(2):165–173

    Google Scholar 

  143. Kim KW, Yoon IY, Chung S, Shin YK, Lee SB, Choi EA, Park JH, Kim JM (2010) Prevalence, comorbidities and risk factors of restless legs syndrome in the Korean elderly population—results from the Korean Longitudinal Study on Health and Aging. J Sleep Res 19(1):87–92

    Article  PubMed  Google Scholar 

  144. Tsuboi Y, Imamura A, Sugimura M, Nakano S, Shirakawa S, Yamada T (2009) Prevalence of restless legs syndrome in a Japanese elderly population. Parkionsonism Relat Dis 15(8):598–601

    Article  Google Scholar 

  145. Erer S, Karli N, Zarifoglu M, Ozcakir A, Yildiz D (2009) The prevalence and clinical features of restless legs syndrome: a door to door population study in Orhangazi, Bursa in Turkey. Neurol India 57(6):729–733

    Article  PubMed  Google Scholar 

  146. Juuti AK, Läärä E, Rajala U, Laakso M, Härkönen P, Keinänen-Kiukaanniemi S, Hiltunen L (2010) Prevalence and associated factors of restless legs in a 57-year-old urban population in northern Finland. Acta Neurol Scand 122(1):63–69

    Article  PubMed  CAS  Google Scholar 

  147. Park YM, Lee HJ, Kang SG, Choi HS, Choi JE, Cho JH, Kim L (2010) Prevalence of idiopathic and secondary restless legs syndrome in Korean Women. Gen Hosp Psychiatry 32(2):164–168

    Article  PubMed  Google Scholar 

  148. Ferri R, Lanuzza B, Cosentino FII, Iero I, Tripodi M, Spada RS, Toscano G, Marelli S, Aricò D, Bella R, Hening WA, Zucconi M (2007) A single question for the rapid screening of restless legs syndrome in the neurological clinical practice. Eur J Neurol 14:1016–1021

    Article  PubMed  CAS  Google Scholar 

  149. Haggstram F, Bigolin AV, Assoni AS, Mezzomo C, Dos Santos IW, Correa MR, Linhares T, Fam CF (2009) Restless legs syndrome study of prevalence among medical school faculty members. Arquivos de Neuro-Psiquiatra 67(3B):822–826

    Google Scholar 

  150. Yilmaz K, Kilincaslan A, Aydin N, Kor D (2011) Prevalence and correlates of restless legs syndrome in adolescents. Dev Med Child Neurol 53(1):40–47

    Article  PubMed  Google Scholar 

  151. Rajaram SS, Walters AS, England SJ, Mehta D, Nizam F (2004) Some children with growing pains may actually have restless legs syndrome. Sleep 27(4):767–773

    PubMed  Google Scholar 

  152. Krishnan PR, Bhatia M, Behari M (2003) Restless legs syndrome in Parkinson’s disease: a case-controlled study. Mov Disord 18(2):181–185

    Article  PubMed  Google Scholar 

  153. Lee JE, Shin HW, Kim KS, Sohn YH (2009) Factors contributing to the development of restless legs syndrome in patients with Parkinson disease. Mov Disord 24(4):579–582

    Article  PubMed  Google Scholar 

  154. Lang AE (1987) Restless legs syndrome and Parkinson’s disease: insights into pathophysiology. Clin Neuropharmacology 10(5):476–478

    Article  CAS  Google Scholar 

  155. Verbaan D, van Rooden SM, van Hilten JJ, Rijsman RM (2010) Prevalence and clinical profile of restless legs syndrome in Parkinson's disease. Mov Disord 25(13):2142–2147

    Article  PubMed  Google Scholar 

  156. Tan EK, Lum SY, Wong MC (2002) Restless legs syndrome in Parkinson’s disease. J Neurol Sci 196(1–2):33–36

    Article  PubMed  CAS  Google Scholar 

  157. Ondo WG, Vuong KD, Jankovic J (2002) Exploring the relationship between Parkinson disease and restless legs syndrome. Arch Neurol 59(3):421–424

    Article  PubMed  Google Scholar 

  158. Nomura T, Inoue Y, Nakashima K (2006) Clinical characterizations of restless legs syndrome in patients with Parkinson’s disease. Journal of Neurological Science 250(1–2):39–44

    Article  Google Scholar 

  159. Ivanenko A, Crabtree VM, Gozal D (2004) Sleep in children with psychiatric disorders. Pediatr Clin North Am 51:51–68

    Article  PubMed  Google Scholar 

  160. Wesström J, Nilsson S, Sundström-Poromaa I, Ulfberg J (2010) Health-related quality of life and restless legs syndrome among women in Sweden. Psychiatry Clin Neurosci 64(5):574–579

    Article  PubMed  Google Scholar 

  161. Trenkwalder C, Kohnen R, Allen RP, Benes H, Ferini-Strambi L, Garcia-Borreguero D, Hadjigeorgiou GM, Happe S, Högl B, Hornyak M, Klein C, Nass A, Montagna P, Oertel WH, O'Keeffe S, Paulus W, Poewe W, Provini F, Pramstaller PP, Sieminski M, Sonka K, Stiasny-Kolster K, de Weerd A, Wetter TC, Winkelmann J, Zucconi M (2007) Clinical trials in restless legs syndrome—recommendations of the European RLS study group (EURLSSG). Move Dis 22(S18):S495–S504

    Google Scholar 

  162. Lattova Z, Keckeis M, Nia S, Maurovich-Horvat, E, Pollmächer, T (2008) Prevalence of restless legs syndrome in a psychiatric population. J Sleep Res 17(Supplement 1):76

    Google Scholar 

  163. Tuncel D, Orhan FO, Karalaslan MF (2009) The levels of depression and somatization in restless legs syndrome. Bull Clin Psychopharma 19(2):143–147

    Google Scholar 

  164. Kalaydjian A, Bienvenu OJ, Hening WA, Allen RP, Eaton WW, Lee HB (2009) Restless legs syndrome and the five-factor model of personality: results from a community sample. Sleep Med 10(6):672–675

    Article  PubMed  CAS  Google Scholar 

  165. Szentikirayli A, Molnar MZ, Czira ME, Deak G, Lindner AV, Szeifert L, Torzsa P, Vamos EP, Zoller R, Mucsi I, Novak M (2009) Association between restless legs syndrome and depression in patients with chronic kidney disease. J Psychosom Res 67(2):173–180

    Article  Google Scholar 

  166. Chervin RD, Archbold KH, Dillon JE, Pituch KJ, Panahi P, Dahl RE, Guilleminault C (2002) Associations between symptoms of inattention, hyperactivity, restless legs, and periodic leg movements. Sleep 25(2):213–218

    PubMed  Google Scholar 

  167. Picchietti DL, Underwood DJ, Farris WA, Walters AS, Shah MM, Dahl RE, Trubnick LJ, Bertocci MA, Wagner M, Hening WA (1999) Further studies on periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder. Mov Disord 14(6):1000–1007

    Article  PubMed  CAS  Google Scholar 

  168. Wagner ML, Walters AS, Fisher BC (2004) Symptoms of attention-deficit/hyperactivity disorder in adults with restless legs syndrome. Sleep 27(8):1499–1504

    PubMed  Google Scholar 

  169. 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 28:1007–1013

    PubMed  Google Scholar 

  170. Richards K, Shue VM, Beck CK, Lambert CW, Bliwise DL (2010) Restless legs syndrome risk factors, behaviors, and diagnoses in persons with early to moderate dementia and sleep disturbance. Behav Sleep Med 8(1):48–61

    Article  PubMed  Google Scholar 

  171. Telarovic S, Reija M, Trkulja V (2007) Restless legs syndrome in hemodialysis patients: association with calcium antagonists. Eur Neurol 58(3):166–169

    Article  PubMed  CAS  Google Scholar 

  172. Unruh ML, Levey AS, D’Ambrosio C, Fink NE, Powe NR, Meyer KB (2004) Restless legs symptoms among incident dialysis patients: association with lower quality of life and shorter survival. American Journal of Kidney Disorders 43(5):900–909

    Article  Google Scholar 

  173. Azar SA, Hatefi R, Talebi M (2007) Evaluation of effect of renal transplantation in treatment of restless legs syndrome. Transplant Proc 39(4):1132–1133

    Article  PubMed  CAS  Google Scholar 

  174. Collado-Seidel V, Kohnen R, Samtleben W, Hillebrand GF, Oertel WH, Trenkwalder C (1998) Clinical and biochemical findings in uremic patients with and without restless legs syndrome. Am J Kidney Dis 31(2):324–328

    Article  PubMed  CAS  Google Scholar 

  175. Bhowmik D, Bhatia M, Gupta S, Agarwal SK, Tiwari SC, Dash SC (2003) Restless legs syndrome in hemodialysis patients in India: a case controlled study. Sleep Med 4(2):143–146

    Article  PubMed  Google Scholar 

  176. Goffredo GS, Gorini CC, Purysko AS, Silva HC, Elias IE (2003) Restless legs syndrome in patients on chronic hemodialysis in a Brazilian city—frequency, biochemical findings, and comorbidities. Arquivos de Neuro-Psiquiatria 61(3B):723–727

    Google Scholar 

  177. La Manna G, Pizza F, Perisci E, Baraldi O, Comai G, Cappuccilli ML, Centofanti F, Carretta E, Plazzi G, Colì L, Montagna P, Stefoni S (2011) Restless legs syndrome enhances cardiovascular risk and mortality in patients with end-stage kidney disease undergoing long-term haemodialysis treatment. Nephrol Dial Transplant 26(6):1976–1983

    Article  PubMed  Google Scholar 

  178. Winkelmann JW, Chertow GM, Lazarus JM (1996) Restless legs syndrome in end-stage renal disease. American J Kidney Dis 28(3):372–378

    Article  Google Scholar 

  179. Kutner NG, Bliwise DL (2002) Restless legs complaint in African-American and Caucasian hemodialysis patients. Sleep Med 3(6):497–500

    Article  PubMed  Google Scholar 

  180. Lee JH, Parker KP, Ansari FP, Bliwise DL (2006) A secondary analysis of racial differences in periodic limb movements in sleep and ferritin in hemodialysis patients. Sleep Med 7(8):646–648

    Article  PubMed  Google Scholar 

  181. Allen RP, Earley CJ (1996) Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep 19:205–213

    PubMed  CAS  Google Scholar 

  182. Garcia-Borreguero D, Allen RP, Kohnen R, Högl B, Trenkwalder C, Oertel W, Hening WA, Paulus W, Rye D, Walters A, Winkelmann J, Earley CJ (2007) Diagnostic standards for dopaminergic augmentation of restless legs syndrome: report from a World Association of Sleep Medicine—International Restless Legs Syndrome Study Group Consensus Conference at the Max Planck Institute. Sleep Med 8:520–530

    Article  PubMed  Google Scholar 

  183. Serafini A, Lorenzut S, Gigli GL, Merlino G, Valente M (2010) The use of rotigotine in the treatment of restless legs syndrome. Ther Adv Nuerol Disord 3(4):241–248

    Article  CAS  Google Scholar 

  184. Silber MH, Girish M, Izurieta R (2003) Pramipexole in the management of restless legs syndrome: an extended study. Sleep 26(7):819–821

    PubMed  Google Scholar 

  185. Stiasny K, Wetter TC, Trenkwalder C, Oertel WH (2000) Restless legs syndrome and its treatment by dopamine agonists. Parkinsonism Relat Disord 7:21–25

    Article  PubMed  Google Scholar 

  186. Bayard M, Avonda T, Wadzinski J (2008) Restless legs syndrome. Am Fam Physician 78(2):235–240

    PubMed  Google Scholar 

  187. Salas RE, Gamaldo CE, Allen RP (2010) Update in restless legs syndrome. Curr Opin Neurol 23:401–406

    PubMed  Google Scholar 

  188. Garcia-Borreguero D, Grunstein R, Sridhar G, Dreykluft T, Montagna P, Dom R, Lainey E, Moorat A, Roberts J (2007) A 52-week open-label study of the long-term safety of ropinirole in patients with restless legs syndrome. Sleep Med 8(7–8):742–752

    Article  PubMed  Google Scholar 

  189. Winkelman JW, Johnston L (2004) Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS). Sleep Med 5:9–14

    Article  PubMed  Google Scholar 

  190. Ferini-Strambi L (2002) Restless legs syndrome augmentation and pramipexole treatment. Sleep Med 3(Suppl):S23–S25

    Article  PubMed  Google Scholar 

  191. Vetrugno R, Contin M, Baruzzi A, Provini F, Plazzi G, Montagna P (2006) Polysomnographic and pharmacokinetic findings in levodopa-induced augmentation of restless legs syndrome. Mov Disord 21:254–258

    Article  PubMed  Google Scholar 

  192. Merlino G, Serafini A, Robiony F, Valente M, Gigli GL (2009) Restless legs syndrome: differential diagnosis and management with rotigotine. Neuropsychiatr Dis Treat 5:67–80

    PubMed  CAS  Google Scholar 

  193. Baldwin CM, Keating GM (2008) Rotigotine transdermal patch: in restless legs syndrome. CNS Drugs 22:797–806

    Article  PubMed  CAS  Google Scholar 

  194. Saletu M, Anderer P, Saletu-Zyhlarz G, Prause W, Semler B, Zoghlami A, Gruber G, Hauer C, Saletu B (2001) Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol 11:153–1461

    Article  PubMed  CAS  Google Scholar 

  195. Boghen D, Lamothe L, Elie R, Godbout R, Montplaisir J (1986) The treatment of the restless legs syndrome with clonazepam: a prospective controlled study. Can J Neurol Sci 13:245–247

    PubMed  CAS  Google Scholar 

  196. Montagna P, Sassoli de Bianchi L, Zucconi M, Cirignotta F, Lugaresi E (1984) Clonazepam and vibration in restless legs syndrome. Acta Neurol Scand 69:428–430

    Article  PubMed  CAS  Google Scholar 

  197. Earley CJ, Silber MH (2010) Restless legs syndrome: understanding its consequences and the need for better treatment. Sleep Med 11:807–815

    Article  PubMed  Google Scholar 

  198. Silber MH, Ehrenberg BL, Allen RP, Buchfuhrer MJ, Earley CJ, Hening WA, Rye DB (2004) An algorithm for the management of restless legs syndrome. Mayo Clin Proc 79(7):916–922

    Article  PubMed  Google Scholar 

  199. Schenck CH, Mahowald MW (1996) Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am J Medicine 100:333–337

    Article  CAS  Google Scholar 

  200. Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G (2002) Treatment of restless legs syndrome with gabapentin: a double-blind, crossover study. Neurology 59:1573–1579

    Article  PubMed  CAS  Google Scholar 

  201. Happe S, Sauter C, Klösch G, Saletu B, Zeitlhofer J (2003) Gabapentin versus ropinirole in the treatment of idiopathic restless legs syndrome. Neuropsychobiology 48:82–86

    Article  PubMed  CAS  Google Scholar 

  202. Happe S, Klosch G, Saletu B, Zeitlhofer J (2001) Treatment of idiopathic restless legs syndrome (RLS) with gabapentin. Neurology 57:1717–1719

    Article  PubMed  CAS  Google Scholar 

  203. Trenkwalder C, Hening WA, Montagna P, Oertel WH, Allen RP, Walters AS, Costa J, Stiasny-Kolster K, Sampaio C (2008) Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice. Mov Disord 23(16):2267–2302

    Article  PubMed  Google Scholar 

  204. Stewart BH, Kugler AR, Thompson PR, Bockbrader HN (1993) A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. Pharm Res 10:276–281

    Article  PubMed  CAS  Google Scholar 

  205. Gidal BE, DeCerce J, Bockbrader HN, Gonzalez J, Kruger S, Pitterle ME, Rutecki P, Ramsay RE (1998) Gabapentin bioavailability: effect of dose and frequency of administration in adult patients with epilepsy. Epilepsy Res 31:91–99

    Article  PubMed  CAS  Google Scholar 

  206. Vollmer KO, von Hodenberg A, Kolle EU (1986) Pharmacokinetics and metabolism of gabapentin in rat, dog and man. Arzneimittelforschung 36:830–839

    PubMed  CAS  Google Scholar 

  207. Lee DO, Ziman RB, Perkins AT, Poceta JS, Walters AS, Barrett RW (2011) A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome. J Clin Sleep Medicine 7(3):282–292

    Google Scholar 

  208. Cundy KC, Annamalai T, Bu L, De Vera J, Estrela J, Luo W, Shirsat P, Torneros A, Yao F, Zou J, Barrett RW, Gallop MA (2004) XP13512 [(+/−)-1-([(alphaisobutanoyloxyethoxy) carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: II. Improved oral bioavailability, dose proportionality, and colonic absorption compared with gabapentin in rats and monkeys. J Pharmacol Exp Ther 311:324–333

    Article  PubMed  CAS  Google Scholar 

  209. Cundy KC, Sastry S, Luo W, Zou J, Moors TL, Canafax DM (2008) Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin. J Clin Pharmacol 48:1378–1388

    Article  PubMed  CAS  Google Scholar 

  210. Lal R, Sukbuntherng J, Luo W, Chen D, Vu A, Tovera J, Cundy KC (2009) Pharmacokinetics of single escalating doses of gabapentin enacarbil in healthy adult volunteers: a randomized sequence, double-blind, placebo-controlled, crossover study. Clin Ther 31:1776–1786

    Article  PubMed  CAS  Google Scholar 

  211. Sommer M, Bachmann CG, Liebetanz KM, Schindehütte J, Tings T, Paulus W (2007) Pregabalin in restless legs syndrome with and without neuropathic pain. Acta Neurol Scand 115(5):347–350

    Article  PubMed  CAS  Google Scholar 

  212. Benes H, Kurella B, Kummer J, Kazenwadel J, Selzer R, Kohnen R (1999) Rapid onset of action of levodopa in restless legs syndrome: a double-blind, randomized, multicenter, crossover trial. Sleep 22(8):1073–1081

    PubMed  CAS  Google Scholar 

  213. Yang C, White DP, Winkelman JW (2005) Antidepressants and periodic leg movements of sleep. Biol Psychiatry 58(6):510–514

    Article  PubMed  CAS  Google Scholar 

  214. Nofzinger EA, Fasiczka A, Berman S, Thase ME (2000) Bupropion SR reduces periodic limb movements associated with arousals from sleep in depressed patients with periodic limb movement disorder. J Clin Psychiatry 61(11):858–862

    Article  PubMed  CAS  Google Scholar 

  215. Sloand JA, Shelley MA, Feigin A, Bernstein P, Monk RD (2004) A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis 43:663–670

    Article  PubMed  CAS  Google Scholar 

  216. Botez MI, Fontaine F, Botez T, Bachevalier J (1977) Folate-responsive neurological and mental disorders: report of 16 cases. Eur Neurol 15:230–246

    Article  Google Scholar 

  217. Hornyak M, Voderholzer U, Hohagen F, Berger M, Riemann D (1998) Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study. Sleep 21:501–505

    PubMed  CAS  Google Scholar 

  218. Eliasson A, Lettieri C (2007) Sequential compression devices for treatment of restless legs syndrome. Medicine 86(6):317–323

    Article  PubMed  Google Scholar 

  219. Sun D, Huang A, Recchia FA, Cui Y, Messina EJ, Koller A, Kaley G (2001) Nitric oxide-mediated arteriolar diation after endothelial deformation. Am J Physiol Heart Circ Physiol 280:H714–H721

    PubMed  CAS  Google Scholar 

  220. Mitchell U, Johnson A, Myrer J (2011) Comparison of two infrared devices in their effectiveness in reducing symptoms associated with RLS. Physiother Theory Pract 27(5):352–359

    Article  PubMed  Google Scholar 

  221. Russell M (2007) Massage therapy and restless legs syndrome. J Bodyw Mov Ther 11(2):146–150

    Article  Google Scholar 

  222. Cui Y, Wang Y, Liu Z (2008) Acupuncture for restless legs syndrome (review). Cochrane Database of Systemic Reviews 8(4):CD006457

    Google Scholar 

  223. Mitchell UH (2011) Nondrug-related aspect of treating Ekbom disease, formerly known as restless legs syndrome. Neuropsychiatric Disease and Treatment 7:251–257

    Article  PubMed  Google Scholar 

  224. Konofal E, Cortese S, Marchand M, Mouren MC, Arnulf I, Lecendreux M (2007) Impact of restless legs syndrome and iron deficiency on attention-deficit/hyperactivity disorder in children. Sleep Med 8:711–715

    Article  PubMed  Google Scholar 

  225. Oner P, Dirik EB, Taner Y, Caykoylu A, Anlar O (2007) Association between low serum ferritin and restless legs syndrome in patients with attention deficit hyperactivity disorder. The Tohoku J Exper Medicine 213:269–276

    Article  CAS  Google Scholar 

  226. Reinhold T, Müller-Riemenschneider F, Willich SN, Brüggenjürgen B (2009) Economic and human costs of restless legs syndrome. Pharmacoeconomics 27(4):267–279

    Article  PubMed  Google Scholar 

  227. Turk F, Quellhorst A, Troche CJ (2004) The economic burden of RLS: a human capital approach. European J Neurology 11(Supplement 2):117

    Google Scholar 

  228. Dodel R, Happe S, Peglau I, Mayer G, Wasem J, Reese JP, Giani G, Geraedts M, Trenkwalder C, Oertel WH, Stiasny-Kolster K (2010) Health economic burden of patients with restless legs syndrome in a german ambulatory setting. Pharmacoeconomics 28(5):381–393

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Vanderbilt–Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Paul Yeh

  2. Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA

    Arthur S. Walters

  3. Dual Diagnostic Treatment Program, Harbor-University of California, Los Angeles Medical Center, Los Angeles, CA, 90502, USA

    John W. Tsuang

  4. Department of Psychiatry, Harbor-University of California, Los Angeles Medical Center, 1,000 West Carson Street, Box 488, Torrance, CA, 90509, USA

    John W. Tsuang

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  1. Paul Yeh
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  2. Arthur S. Walters
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  3. John W. Tsuang
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Correspondence to John W. Tsuang.

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Yeh, P., Walters, A.S. & Tsuang, J.W. Restless legs syndrome: a comprehensive overview on its epidemiology, risk factors, and treatment. Sleep Breath 16, 987–1007 (2012). https://doi.org/10.1007/s11325-011-0606-x

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  • DOI: https://doi.org/10.1007/s11325-011-0606-x

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