UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

不安腿综合征

Author
Daniel Tarsy, MD
Section Editors
Howard I Hurtig, MD
Marc C Patterson, MD, FRACP
Ruth Benca, MD, PhD
Deputy Editor
April F Eichler, MD, MPH
Translators
叶红, 主治医师

引言

不安腿综合征(restless legs syndrome, RLS)是指与使人不适的感觉异常相关的自发的持续性腿部运动症状[1]。患者迫切想活动下肢，夜间及静息状态下症状加重，活动可使症状缓解。睡眠障碍和常常与之相关的睡眠中下肢不自主抽动[也称为睡眠期周期性肢动(periodic leg movements of sleep, PLMS)]较为常见。夜间腿痉挛是另外一种疾病，将在别处讨论。 (参见“夜间腿部痛性痉挛”)

流行病学

5%-15%的人有RLS的轻度症状，患病率数据根据所调查的人群和入选标准对症状严重程度的要求不同而变化较大[2-5]。

在一项关于根据标准的诊断原则诊断出的RLS的群体研究中，来自美国和5个欧洲国家(法国、德国、意大利、西班牙和英国)的15391例受试者(≥18岁)完成了问卷调查，得出的结果如下[6]：

  • 7.2%的受试者报告出现发作频率不同的RLS症状。
  • RLS症状一周至少出现2次，且有2.7%的受试者报告RLS给其带来中度至重度痛苦。
  • RLS在女性中的患病率大概是男性的2倍。
  • 79岁及以前，RLS的发病率随年龄增长而升高，79岁后又呈下降趋势。

既往的一项调查也发现RLS(每月至少发病5晚)的患病率随着年龄增大而升高，18-29岁是3%，30-79岁是10%，而80岁及以上则是19%[7]。生育次数增加可能使RLS风险增加[8]。

                                    

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: 2017-06 . | This topic last updated: 2017-05-12.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. O'Keeffe ST. Restless legs syndrome. A review. Arch Intern Med 1996; 156:243.
  2. Lavigne GJ, Montplaisir JY. Restless legs syndrome and sleep bruxism: prevalence and association among Canadians. Sleep 1994; 17:739.
  3. Nichols DA, Allen RP, Grauke JH, et al. Restless legs syndrome symptoms in primary care: a prevalence study. Arch Intern Med 2003; 163:2323.
  4. Högl B, Kiechl S, Willeit J, et al. Restless legs syndrome: a community-based study of prevalence, severity, and risk factors. Neurology 2005; 64:1920.
  5. Allen RP, Bharmal M, Calloway M. Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Mov Disord 2011; 26:114.
  6. Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005; 165:1286.
  7. Phillips B, Young T, Finn L, et al. Epidemiology of restless legs symptoms in adults. Arch Intern Med 2000; 160:2137.
  8. Berger K, Luedemann J, Trenkwalder C, et al. Sex and the risk of restless legs syndrome in the general population. Arch Intern Med 2004; 164:196.
  9. Picchietti D, Allen RP, Walters AS, et al. Restless legs syndrome: prevalence and impact in children and adolescents--the Peds REST study. Pediatrics 2007; 120:253.
  10. Walters AS, Hickey K, Maltzman J, et al. A questionnaire study of 138 patients with restless legs syndrome: the 'Night-Walkers' survey. Neurology 1996; 46:92.
  11. Kotagal S, Silber MH. Childhood-onset restless legs syndrome. Ann Neurol 2004; 56:803.
  12. Pullen SJ, Wall CA, Angstman ER, et al. Psychiatric comorbidity in children and adolescents with restless legs syndrome: a retrospective study. J Clin Sleep Med 2011; 7:587.
  13. Lee HB, Hening WA, Allen RP, et al. Restless legs syndrome is associated with DSM-IV major depressive disorder and panic disorder in the community. J Neuropsychiatry Clin Neurosci 2008; 20:101.
  14. Winkelmann J, Prager M, Lieb R, et al. "Anxietas tibiarum". Depression and anxiety disorders in patients with restless legs syndrome. J Neurol 2005; 252:67.
  15. Hornyak M. Depressive disorders in restless legs syndrome: epidemiology, pathophysiology and management. CNS Drugs 2010; 24:89.
  16. Hening W, Allen R, Earley C, et al. The treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine Review. Sleep 1999; 22:970.
  17. Montplaisir J, Boucher S, Poirier G, et al. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. Mov Disord 1997; 12:61.
  18. Ondo WG, Vuong KD, Wang Q. Restless legs syndrome in monozygotic twins: clinical correlates. Neurology 2000; 55:1404.
  19. Pichler I, Marroni F, Volpato CB, et al. Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate. Am J Hum Genet 2006; 79:716.
  20. Chen S, Ondo WG, Rao S, et al. Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p. Am J Hum Genet 2004; 74:876.
  21. Lohmann-Hedrich K, Neumann A, Kleensang A, et al. Evidence for linkage of restless legs syndrome to chromosome 9p: are there two distinct loci? Neurology 2008; 70:686.
  22. Desautels A, Turecki G, Montplaisir J, et al. Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q. Am J Hum Genet 2001; 69:1266.
  23. Desautels A, Turecki G, Montplaisir J, et al. Restless legs syndrome: confirmation of linkage to chromosome 12q, genetic heterogeneity, and evidence of complexity. Arch Neurol 2005; 62:591.
  24. Bonati MT, Ferini-Strambi L, Aridon P, et al. Autosomal dominant restless legs syndrome maps on chromosome 14q. Brain 2003; 126:1485.
  25. Levchenko A, Provost S, Montplaisir JY, et al. A novel autosomal dominant restless legs syndrome locus maps to chromosome 20p13. Neurology 2006; 67:900.
  26. Winkelmann J, Schormair B, Lichtner P, et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 2007; 39:1000.
  27. Schormair B, Kemlink D, Roeske D, et al. PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome. Nat Genet 2008; 40:946.
  28. Yang Q, Li L, Yang R, et al. Family-based and population-based association studies validate PTPRD as a risk factor for restless legs syndrome. Mov Disord 2011; 26:516.
  29. Stefansson H, Rye DB, Hicks A, et al. A genetic risk factor for periodic limb movements in sleep. N Engl J Med 2007; 357:639.
  30. Schöls L, Haan J, Riess O, et al. Sleep disturbance in spinocerebellar ataxias: is the SCA3 mutation a cause of restless legs syndrome? Neurology 1998; 51:1603.
  31. Chokroverty S, Jankovic J. Restless legs syndrome: a disease in search of identity. Neurology 1999; 52:907.
  32. Clemens S, Rye D, Hochman S. Restless legs syndrome: revisiting the dopamine hypothesis from the spinal cord perspective. Neurology 2006; 67:125.
  33. Ruottinen HM, Partinen M, Hublin C, et al. An FDOPA PET study in patients with periodic limb movement disorder and restless legs syndrome. Neurology 2000; 54:502.
  34. Turjanski N, Lees AJ, Brooks DJ. Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies. Neurology 1999; 52:932.
  35. Cervenka S, Pålhagen SE, Comley RA, et al. Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding. Brain 2006; 129:2017.
  36. Eisensehr I, Wetter TC, Linke R, et al. Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome. Neurology 2001; 57:1307.
  37. Ondo WG, Vuong KD, Jankovic J. Exploring the relationship between Parkinson disease and restless legs syndrome. Arch Neurol 2002; 59:421.
  38. Taheri S, Zeitzer JM, Mignot E. The role of hypocretins (orexins) in sleep regulation and narcolepsy. Annu Rev Neurosci 2002; 25:283.
  39. Allen RP, Mignot E, Ripley B, et al. Increased CSF hypocretin-1 (orexin-A) in restless legs syndrome. Neurology 2002; 59:639.
  40. EKBOM KA. Restless legs syndrome. Neurology 1960; 10:868.
  41. O'Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing 1994; 23:200.
  42. Earley CJ, Connor JR, Beard JL, et al. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 2000; 54:1698.
  43. Allen RP, Barker PB, Wehrl FW, et al. MRI measurement of brain iron in patients with restless legs syndrome. Neurology 2001; 56:263.
  44. Silber MH, Richardson JW. Multiple blood donations associated with iron deficiency in patients with restless legs syndrome. Mayo Clin Proc 2003; 78:52.
  45. Connor JR, Ponnuru P, Wang XS, et al. Profile of altered brain iron acquisition in restless legs syndrome. Brain 2011; 134:959.
  46. Connor JR, Boyer PJ, Menzies SL, et al. Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology 2003; 61:304.
  47. Connor JR, Wang XS, Patton SM, et al. Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome. Neurology 2004; 62:1563.
  48. Trotti LM, Bhadriraju S, Becker LA. Iron for restless legs syndrome. Cochrane Database Syst Rev 2012; :CD007834.
  49. Walker S, Fine A, Kryger MH. Sleep complaints are common in a dialysis unit. Am J Kidney Dis 1995; 26:751.
  50. Thorp ML. Restless legs syndrome. Int J Artif Organs 2001; 24:755.
  51. Kavanagh D, Siddiqui S, Geddes CC. Restless legs syndrome in patients on dialysis. Am J Kidney Dis 2004; 43:763.
  52. Harris DC, Chapman JR, Stewart JH, et al. Low dose erythropoietin in maintenance haemodialysis: improvement in quality of life and reduction in true cost of haemodialysis. Aust N Z J Med 1991; 21:693.
  53. Sloand JA, Shelly MA, Feigin A, et al. A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis 2004; 43:663.
  54. Collado-Seidel V, Kohnen R, Samtleben W, et al. Clinical and biochemical findings in uremic patients with and without restless legs syndrome. Am J Kidney Dis 1998; 31:324.
  55. O'Hare JA, Abuaisha F, Geoghegan M. Prevalence and forms of neuropathic morbidity in 800 diabetics. Ir J Med Sci 1994; 163:132.
  56. Lopes LA, Lins Cde M, Adeodato VG, et al. Restless legs syndrome and quality of sleep in type 2 diabetes. Diabetes Care 2005; 28:2633.
  57. Merlino G, Fratticci L, Valente M, et al. Association of restless legs syndrome in type 2 diabetes: a case-control study. Sleep 2007; 30:866.
  58. Müller-Felber W, Landgraf R, Wagner S, et al. Follow-up study of sensory-motor polyneuropathy in type 1 (insulin-dependent) diabetic subjects after simultaneous pancreas and kidney transplantation and after graft rejection. Diabetologia 1991; 34 Suppl 1:S113.
  59. Auger C, Montplaisir J, Duquette P. Increased frequency of restless legs syndrome in a French-Canadian population with multiple sclerosis. Neurology 2005; 65:1652.
  60. Italian REMS Study Group, Manconi M, Ferini-Strambi L, et al. Multicenter case-control study on restless legs syndrome in multiple sclerosis: the REMS study. Sleep 2008; 31:944.
  61. Deriu M, Cossu G, Molari A, et al. Restless legs syndrome in multiple sclerosis: a case-control study. Mov Disord 2009; 24:697.
  62. Gómez-Choco MJ, Iranzo A, Blanco Y, et al. Prevalence of restless legs syndrome and REM sleep behavior disorder in multiple sclerosis. Mult Scler 2007; 13:805.
  63. Li Y, Munger KL, Batool-Anwar S, et al. Association of multiple sclerosis with restless legs syndrome and other sleep disorders in women. Neurology 2012; 78:1500.
  64. Garcia-Borreguero D, Odin P, Serrano C. Restless legs syndrome and PD: a review of the evidence for a possible association. Neurology 2003; 61:S49.
  65. Krishnan PR, Bhatia M, Behari M. Restless legs syndrome in Parkinson's disease: a case-controlled study. Mov Disord 2003; 18:181.
  66. Lee JE, Shin HW, Kim KS, Sohn YH. Factors contributing to the development of restless legs syndrome in patients with Parkinson disease. Mov Disord 2009; 24:579.
  67. Guerreiro TM, Nishikawa DR, Ferreira LC, et al. Restless legs syndrome in Parkinson's disease: clinical characteristics and biochemical correlations. Arq Neuropsiquiatr 2010; 68:869.
  68. Lang AE, Johnson K. Akathisia in idiopathic Parkinson's disease. Neurology 1987; 37:477.
  69. Tan EK, Lum SY, Wong MC. Restless legs syndrome in Parkinson's disease. J Neurol Sci 2002; 196:33.
  70. Gjerstad MD, Tysnes OB, Larsen JP. Increased risk of leg motor restlessness but not RLS in early Parkinson disease. Neurology 2011; 77:1941.
  71. Angelini M, Negrotti A, Marchesi E, et al. A study of the prevalence of restless legs syndrome in previously untreated Parkinson's disease patients: absence of co-morbid association. J Neurol Sci 2011; 310:286.
  72. Arnulf I, Morgan J. Not all that goes "bump in the night" is RLS: leg motor restlessness in PD. Neurology 2011; 77:1936.
  73. Peralta CM, Frauscher B, Seppi K, et al. Restless legs syndrome in Parkinson's disease. Mov Disord 2009; 24:2076.
  74. García-Borreguero D, Allen RP, Benes H, et al. Augmentation as a treatment complication of restless legs syndrome: concept and management. Mov Disord 2007; 22 Suppl 18:S476.
  75. Comella CL, Goetz CG. Akathisia in Parkinson's disease. Mov Disord 1994; 9:545.
  76. Poewe W, Högl B. Akathisia, restless legs and periodic limb movements in sleep in Parkinson's disease. Neurology 2004; 63:S12.
  77. Ekbom KA. Restless legs syndrome. Acta Med Scan Suppl 1945; 158:4.
  78. Goodman JD, Brodie C, Ayida GA. Restless leg syndrome in pregnancy. BMJ 1988; 297:1101.
  79. Suzuki K, Ohida T, Sone T, et al. The prevalence of restless legs syndrome among pregnant women in Japan and the relationship between restless legs syndrome and sleep problems. Sleep 2003; 26:673.
  80. Manconi M, Govoni V, De Vito A, et al. Restless legs syndrome and pregnancy. Neurology 2004; 63:1065.
  81. Dzaja A, Wehrle R, Lancel M, Pollmächer T. Elevated estradiol plasma levels in women with restless legs during pregnancy. Sleep 2009; 32:169.
  82. Salih AM, Gray RE, Mills KR, Webley M. A clinical, serological and neurophysiological study of restless legs syndrome in rheumatoid arthritis. Br J Rheumatol 1994; 33:60.
  83. Gudbjörnsson B, Broman JE, Hetta J, Hällgren R. Sleep disturbances in patients with primary Sjögren's syndrome. Br J Rheumatol 1993; 32:1072.
  84. Hassan N, Pineau CA, Clarke AE, et al. Systemic lupus and risk of restless legs syndrome. J Rheumatol 2011; 38:874.
  85. Yunus MB, Aldag JC. Restless legs syndrome and leg cramps in fibromyalgia syndrome: a controlled study. BMJ 1996; 312:1339.
  86. Ondo W, Tan EK, Mansoor J. Rheumatologic serologies in secondary restless legs syndrome. Mov Disord 2000; 15:321.
  87. Kanter AH. The effect of sclerotherapy on restless legs syndrome. Dermatol Surg 1995; 21:328.
  88. Poynard T, Valterio C. Meta-analysis of hydroxyethylrutosides in the treatment of chronic venous insufficiency. Vasa 1994; 23:244.
  89. Chaudhuri KR, Appiah-Kubi LS, Trenkwalder C. Restless legs syndrome. J Neurol Neurosurg Psychiatry 2001; 71:143.
  90. Lutz EG. Restless legs, anxiety and caffeinism. J Clin Psychiatry 1978; 39:693.
  91. LaBan MM, Viola SL, Femminineo AF, Taylor RS. Restless legs syndrome associated with diminished cardiopulmonary compliance and lumbar spinal stenosis--a motor concomitant of "Vesper's curse". Arch Phys Med Rehabil 1990; 71:384.
  92. Markkula J, Lauerma H. Mianserin and restless legs. Int Clin Psychopharmacol 1997; 12:53.
  93. Hattan E, Chalk C, Postuma RB. Is there a higher risk of restless legs syndrome in peripheral neuropathy? Neurology 2009; 72:955.
  94. Gao X, Schwarzschild MA, Wang H, Ascherio A. Obesity and restless legs syndrome in men and women. Neurology 2009; 72:1255.
  95. Rajabally YA, Shah RS. Restless legs syndrome in chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 2010; 42:252.
  96. Limousin N, Blasco H, Corcia P, et al. The high frequency of restless legs syndrome in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2011; 12:303.
  97. Karatas M. Restless legs syndrome and periodic limb movements during sleep: diagnosis and treatment. Neurologist 2007; 13:294.
  98. Walters AS, Rye DB. Review of the relationship of restless legs syndrome and periodic limb movements in sleep to hypertension, heart disease, and stroke. Sleep 2009; 32:589.
  99. Coelho FM, Georgsson H, Narayansingh M, et al. Higher prevalence of periodic limb movements of sleep in patients with history of stroke. J Clin Sleep Med 2010; 6:428.
  100. Yumino D, Wang H, Floras JS, et al. Relation of periodic leg movements during sleep and mortality in patients with systolic heart failure. Am J Cardiol 2011; 107:447.
  101. Koo BB, Blackwell T, Ancoli-Israel S, et al. Association of incident cardiovascular disease with periodic limb movements during sleep in older men: outcomes of sleep disorders in older men (MrOS) study. Circulation 2011; 124:1223.
  102. Hornyak M, Feige B, Voderholzer U, et al. Polysomnography findings in patients with restless legs syndrome and in healthy controls: a comparative observational study. Sleep 2007; 30:861.
  103. Hening WA, Allen RP, Earley CJ, et al. An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep 2004; 27:560.
  104. Lesage S, Hening WA. The restless legs syndrome and periodic limb movement disorder: a review of management. Semin Neurol 2004; 24:249.
  105. American Academy of Sleep Medicine. International classification of sleep disorders, 2nd ed: Diagnostic and coding manual, Westchester, IL, American Academy of Sleep Medicine, 2005.
  106. Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003; 4:101.
  107. Chesson A Jr, Hartse K, Anderson WM, et al. Practice parameters for the evaluation of chronic insomnia. An American Academy of Sleep Medicine report. Standards of Practice Committee of the American Academy of Sleep Medicine. Sleep 2000; 23:237.
  108. Walters AS, Hening W, Rubinstein M, Chokroverty S. A clinical and polysomnographic comparison of neuroleptic-induced akathisia and the idiopathic restless legs syndrome. Sleep 1991; 14:339.
  109. Dressler D, Thompson PD, Gledhill RF, Marsden CD. The syndrome of painful legs and moving toes. Mov Disord 1994; 9:13.
  110. Scholz H, Trenkwalder C, Kohnen R, et al. Dopamine agonists for restless legs syndrome. Cochrane Database Syst Rev 2011; :CD006009.
  111. Aurora RN, Kristo DA, Bista SR, et al. 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: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep 2012; 35:1039.
  112. Wilt TJ, MacDonald R, Ouellette J, et al. Treatment for restless legs syndrome. Agency for Healthcare Research and Quality (US). www.ncbi.nlm.nih.gov/books/NBK115385/ (Accessed on January 22, 2013).
  113. Silber MH, Ehrenberg BL, Allen RP, et al. An algorithm for the management of restless legs syndrome. Mayo Clin Proc 2004; 79:916.
  114. Earley CJ. Clinical practice. Restless legs syndrome. N Engl J Med 2003; 348:2103.
  115. Leschziner G, Gringras P. Restless legs syndrome. BMJ 2012; 344:e3056.
  116. Mitchell UH. Nondrug-related aspect of treating Ekbom disease, formerly known as restless legs syndrome. Neuropsychiatr Dis Treat 2011; 7:251.
  117. Nofzinger EA, Fasiczka A, Berman S, Thase ME. Bupropion SR reduces periodic limb movements associated with arousals from sleep in depressed patients with periodic limb movement disorder. J Clin Psychiatry 2000; 61:858.
  118. Jaber BL, Schiller B, Burkart JM, et al. Impact of short daily hemodialysis on restless legs symptoms and sleep disturbances. Clin J Am Soc Nephrol 2011; 6:1049.
  119. Trenkwalder C, Garcia-Borreguero D, Montagna P, et al. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry 2004; 75:92.
  120. Walters AS, Ondo WG, Dreykluft T, et al. Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel-group, placebo-controlled study. Mov Disord 2004; 19:1414.
  121. Bogan RK, Fry JM, Schmidt MH, et al. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc 2006; 81:17.
  122. Winkelman JW, Sethi KD, Kushida CA, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology 2006; 67:1034.
  123. Stiasny K, Möller JC, Oertel WH. Safety of pramipexole in patients with restless legs syndrome. Neurology 2000; 55:1589.
  124. Tippmann-Peikert M, Park JG, Boeve BF, et al. Pathologic gambling in patients with restless legs syndrome treated with dopaminergic agonists. Neurology 2007; 68:301.
  125. Silber MH, Girish M, Izurieta R. Pramipexole in the management of restless legs syndrome: an extended study. Sleep 2003; 26:819.
  126. Winkelman JW, Johnston L. Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS). Sleep Med 2004; 5:9.
  127. Ondo W, Romanyshyn J, Vuong KD, Lai D. Long-term treatment of restless legs syndrome with dopamine agonists. Arch Neurol 2004; 61:1393.
  128. Stiasny K, Röbbecke J, Schüler P, Oertel WH. Treatment of idiopathic restless legs syndrome (RLS) with the D2-agonist cabergoline--an open clinical trial. Sleep 2000; 23:349.
  129. Chaudhuri KR. Restless legs syndrome. N Engl J Med 2003; 349:815.
  130. Stiasny-Kolster K, Benes H, Peglau I, et al. Effective cabergoline treatment in idiopathic restless legs syndrome. Neurology 2004; 63:2272.
  131. Oertel WH, Benes H, Bodenschatz R, et al. Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR). Neurology 2006; 67:1040.
  132. Yamamoto M, Uesugi T, Nakayama T. Dopamine agonists and cardiac valvulopathy in Parkinson disease: a case-control study. Neurology 2006; 67:1225.
  133. Van Camp G, Flamez A, Cosyns B, et al. Treatment of Parkinson's disease with pergolide and relation to restrictive valvular heart disease. Lancet 2004; 363:1179.
  134. FDA Announces Voluntary Withdrawal of Pergolide Products. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108877.htm.
  135. Scholz H, Trenkwalder C, Kohnen R, et al. Levodopa for restless legs syndrome. Cochrane Database Syst Rev 2011; :CD005504.
  136. Akpinar S. Restless legs syndrome treatment with dopaminergic drugs. Clin Neuropharmacol 1987; 10:69.
  137. von Scheele C. Levodopa in restless legs. Lancet 1986; 2:426.
  138. Trenkwalder C, Stiasny K, Pollmächer T, et al. L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind, crossover trial. Sleep 1995; 18:681.
  139. Guilleminault C, Cetel M, Philip P. Dopaminergic treatment of restless legs and rebound phenomenon. Neurology 1993; 43:445.
  140. von Scheele C, Kempi V. Long-term effect of dopaminergic drugs in restless legs. A 2-year follow-up. Arch Neurol 1990; 47:1223.
  141. Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep 1996; 19:205.
  142. Earley CJ, Allen RP. Pergolide and carbidopa/levodopa treatment of the restless legs syndrome and periodic leg movements in sleep in a consecutive series of patients. Sleep 1996; 19:801.
  143. Collado-Seidel V, Kazenwadel J, Wetter TC, et al. A controlled study of additional sr-L-dopa in L-dopa-responsive restless legs syndrome with late-night symptoms. Neurology 1999; 52:285.
  144. Schenck CH, Mahowald MW. Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am J Med 1996; 100:333.
  145. Montplaisir J, Godbout R, Boghen D, et al. Familial restless legs with periodic movements in sleep: electrophysiologic, biochemical, and pharmacologic study. Neurology 1985; 35:130.
  146. Montagna P, Sassoli de Bianchi L, Zucconi M, et al. Clonazepam and vibration in restless legs syndrome. Acta Neurol Scand 1984; 69:428.
  147. Read DJ, Feest TG, Nassim MA. Clonazepam: effective treatment for restless legs syndrome in uraemia. Br Med J (Clin Res Ed) 1981; 283:885.
  148. Kushida CA, Becker PM, Ellenbogen AL, et al. Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS. Neurology 2009; 72:439.
  149. Kushida CA, Walters AS, Becker P, et al. A randomized, double-blind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome. Sleep 2009; 32:159.
  150. Happe S, Klösch G, Saletu B, Zeitlhofer J. Treatment of idiopathic restless legs syndrome (RLS) with gabapentin. Neurology 2001; 57:1717.
  151. Garcia-Borreguero D, Larrosa O, de la Llave Y, et al. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology 2002; 59:1573.
  152. Thorp ML, Morris CD, Bagby SP. A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients. Am J Kidney Dis 2001; 38:104.
  153. Hening WA, Walters A, Kavey N, et al. Dyskinesias while awake and periodic movements in sleep in restless legs syndrome: treatment with opioids. Neurology 1986; 36:1363.
  154. Walters AS, Wagner ML, Hening WA, et al. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep 1993; 16:327.
  155. Walters AS, Winkelmann J, Trenkwalder C, et al. Long-term follow-up on restless legs syndrome patients treated with opioids. Mov Disord 2001; 16:1105.
  156. Garcia-Borreguero D, Larrosa O, Williams AM, et al. Treatment of restless legs syndrome with pregabalin: a double-blind, placebo-controlled study. Neurology 2010; 74:1897.
  157. Telstad W, Sørensen O, Larsen S, et al. Treatment of the restless legs syndrome with carbamazepine: a double blind study. Br Med J (Clin Res Ed) 1984; 288:444.
  158. Wagner ML, Walters AS, Coleman RG, et al. Randomized, double-blind, placebo-controlled study of clonidine in restless legs syndrome. Sleep 1996; 19:52.
  159. Derom E, Elinck W, Buylaert W, van der Straeten M. Which beta-blocker for the restless leg? Lancet 1984; 1:857.
  160. Evidente VG, Adler CH, Caviness JN, et al. Amantadine is beneficial in restless legs syndrome. Mov Disord 2000; 15:324.