Restless legs syndrome: Clinical presentation diagnosis and treatment

Sleep Medicine

Volumn 16, Issue 6, 2015, Pages 678-690

  Wijemanne, Subhashie ^a   Jankovic, Joseph ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Augmentation; Dopamine agonist; Gabapentin; Methadone; Pramipexole; Restless legs syndrome; Ropinirole; Rotigotine

Indexed keywords

CABERGOLINE; CLONAZEPAM; CODEINE; DECARBOXYLASE INHIBITOR; DEXTROPROPOXYPHENE; DOPAMINE RECEPTOR STIMULATING AGENT; FERRIC CARBOXYMALTOSE; FERRIC GLUCONATE; GABAPENTIN; GABAPENTIN ENACARBIL; HYDROCODONE; IRON; IRON DEXTRAN; IRON SACCHARATE; LEVODOPA; METHADONE; NALOXONE PLUS OXYCODONE; NARCOTIC ANALGESIC AGENT; OXYCODONE; PENTAZOCINE; PERGOLIDE; PETHIDINE; PLACEBO; PRAMIPEXOLE; PREGABALIN; ROPINIROLE; ROTIGOTINE; TEMAZEPAM; TRAMADOL; UNINDEXED DRUG; 4 AMINOBUTYRIC ACID; AMINE; BENZOTHIAZOLE DERIVATIVE; CYCLOHEXANECARBOXYLIC ACID DERIVATIVE; INDOLE DERIVATIVE; TETRALIN DERIVATIVE; THIOPHENE DERIVATIVE;

ACUPUNCTURE; AEROBIC EXERCISE; ANAPHYLAXIS; APPLICATION SITE REACTION; BEDTIME DOSAGE; BLOATING; BRAIN DEPTH STIMULATION; CLINICAL FEATURE; COMPULSION; DIZZINESS; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG PROTEIN BINDING; DRUG WITHDRAWAL; EVENING DOSAGE; FAMILY HISTORY; FATIGUE; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENETIC ASSOCIATION; GENETIC VARIABILITY; HEADACHE; HUMAN; HYPERSEXUALITY; IMPULSE CONTROL DISORDER; INSOMNIA; IRON THERAPY; LONG TERM CARE; MASSAGE; MUSCLE CRAMP; NAUSEA; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOGENESIS; PATHOLOGICAL GAMBLING; PERIODIC LIMB MOVEMENT DISORDER; PERIPHERAL EDEMA; PHOTOTHERAPY; PRACTICE GUIDELINE; PREGNANCY; PREVALENCE; PRIORITY JOURNAL; RESISTANCE TRAINING; RESTLESS LEGS SYNDROME; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SKIN MANIFESTATION; SOMNOLENCE; SUICIDAL IDEATION; UNSPECIFIED SIDE EFFECT; VOMITING; VOXEL BASED MORPHOMETRY; WEIGHT GAIN;

AMINES; ANALGESICS, OPIOID; BENZOTHIAZOLES; CYCLOHEXANECARBOXYLIC ACIDS; DOPAMINE AGONISTS; GAMMA-AMINOBUTYRIC ACID; HUMANS; INDOLES; METHADONE; RESTLESS LEGS SYNDROME; TETRAHYDRONAPHTHALENES; THIOPHENES;

EID: 84938956251     PISSN: 13899457     EISSN: 18785506     Source Type: Journal    
DOI: 10.1016/j.sleep.2015.03.002     Document Type: Review

References (217)

1. Rye D.B., Trotti L.M. Restless legs syndrome and periodic leg movements of sleep. Neurol Clin 2012, 30:1137-1166.
2. Rizzo V., Arico I., Liotta G., et al. Impairment of sensory-motor integration in patients affected by RLS. J Neurol 2010, 257:1979-1985.
3. Patel N., Jankovic J., Hallett M. Sensory aspects of movement disorders. Lancet Neurol 2014, 13:100-112.
4. Ku J., Cho Y.W., Lee Y.S., et al. Functional connectivity alternation of the thalamus in restless legs syndrome patients during the asymptomatic period: a resting-state connectivity study using functional magnetic resonance imaging. Sleep Med 2014, 15:289-294.
5. Coccagna G., Vetrugno R., Lombardi C., et al. Restless legs syndrome: an historical note. Sleep Med 2004, 5:279-283.
6. Silber M.H., Becker P.M., Earley C., et al. Willis-Ekbom Disease Foundation revised consensus statement on the management of restless legs syndrome. Mayo Clin Proc 2013, 88:977-986.
7. 2012 revised diagnostic criteria International Restless Legs Syndrome Study Group, accessed 01.01.12. http://irlssg.org/diagnostic-criteria/.
8. Allen R.P., Picchietti D.L., Garcia-Borreguero D., et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria - history, rationale, description, and significance. Sleep Med 2014, 15:860-873.
9. Allen R.P., Picchietti D., Hening W.A., 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, 4:101-119.
10. Rana A.Q., Khan F., Mosabbir A., et al. Differentiating nocturnal leg cramps and restless legs syndrome. Expert Rev Neurother 2014, 14:813-818.
11. Ondo W., Jankovic J. Restless legs syndrome: clinicoetiologic correlates. Neurology 1996, 47:1435-1441.
12. Kerr S., McKinon W., Bentley A. Descriptors of restless legs syndrome sensations. Sleep Med 2012, 13:409-413.
13. Karroum E.G., Leu-Semenescu S., Arnulf I. Topography of the sensations in primary restless legs syndrome. J Neurol Sci 2012, 320:26-31.
14. Jankovic J. Treatment of hyperkinetic movement disorders. Lancet Neurol 2009, 8:844-856.
15. Stiasny-Kolster K., Kohnen R., Moller J.C., et al. Validation of the "L-DOPA test" for diagnosis of restless legs syndrome. Mov Disord 2006, 21:1333-1339.
16. 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, 12:61-65.
17. Aurora R.N., Kristo D.A., Bista S.R., 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, 35:1039-1062.
18. Stiasny K., Oertel W.H., Trenkwalder C. Clinical symptomatology and treatment of restless legs syndrome and periodic limb movement disorder. Sleep Med Rev 2002, 6:253-265.
19. Zucconi M., Ferri R., Allen R., et al. The official World Association of Sleep Medicine (WASM) standards for recording and scoring periodic leg movements in sleep (PLMS) and wakefulness (PLMW) developed in collaboration with a task force from the International Restless Legs Syndrome Study Group (IRLSSG). Sleep Med 2006, 7:175-183.
20. Ferri R., Fulda S., Manconi M., et al. Night-to-night variability of periodic leg movements during sleep in restless legs syndrome and periodic limb movement disorder: comparison between the periodicity index and the PLMS index. Sleep Med 2013, 14:293-296.
21. Earley C.J., Silber M.H. Restless legs syndrome: understanding its consequences and the need for better treatment. Sleep Med 2010, 11:807-815.
22. Abetz L., Allen R., Follet A., et al. Evaluating the quality of life of patients with restless legs syndrome. Clin Ther 2004, 26:925-935.
23. Allen R.P., 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, 26:114-120.
24. Lee H.B., Ramsey C.M., Spira A.P., et al. Comparison of cognitive functioning among individuals with treated restless legs syndrome (RLS), untreated RLS, and no RLS. J Neuropsychiatry Clin Neurosci 2014, 26:87-91.
25. Trenkwalder C., Paulus W. Restless legs syndrome: pathophysiology, clinical presentation and management. Nat Rev Neurol 2010, 6:337-346.
26. Lin C.H., Sy H.N., Chang H.W., et al. Restless legs syndrome is associated with cardio/cerebrovascular events and mortality in end-stage renal disease. Eur J Neurol 2014, 22:142-149.
27. Szentkiralyi A., Winter A.C., Schurks M., et al. Restless legs syndrome and all-cause mortality in four prospective cohort studies. BMJ Open 2012, 2.
28. Li Y., Wang W., Winkelman J.W., et al. Prospective study of restless legs syndrome and mortality among men. Neurology 2013, 81:52-59.
29. Allen R.P., Walters A.S., Montplaisir J., et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005, 165:1286-1292.
30. Tan E.K., Seah A., See S.J., et al. Restless legs syndrome in an Asian population: a study in Singapore. Mov Disord 2001, 16:577-579.
31. Cho S.J., Hong J.P., Hahm B.J., et al. Restless legs syndrome in a community sample of Korean adults: prevalence, impact on quality of life, and association with DSM-IV psychiatric disorders. Sleep 2009, 32:1069-1076.
32. Ohayon M.M., O'Hara R., Vitiello M.V. Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Med Rev 2012, 16:283-295.
33. Hogl B., Kiechl S., Willeit J., et al. Restless legs syndrome: a community-based study of prevalence, severity, and risk factors. Neurology 2005, 64:1920-1924.
34. Ondo W.G., Vuong K.D., Jankovic J. Exploring the relationship between Parkinson disease and restless legs syndrome. Arch Neurol 2002, 59:421-424.
35. Bhalsing K., Suresh K., Muthane U.B., Pal P.K. Prevalence and profile of Restless Legs Syndrome in Parkinson's disease and other neurodegenerative disorders: a case-control study. Parkinsonism Relat Disord 2013, 19:426-430.
36. Peeraully T., Tan E.K. Linking restless legs syndrome with Parkinson's disease: clinical, imaging and genetic evidence. Transl Neurodegener 2012, 1:6.
37. Aquino C.C., Mestre T., Lang A.E. Restless genital syndrome in Parkinson disease. JAMA Neurol 2014, 71:1559-1561.
38. Wong J.C., Li Y., Schwarzschild M.A., et al. Restless legs syndrome: an early clinical feature of Parkinson disease in men. Sleep 2014, 37:369-372.
39. Winkelmann J., Wetter T.C., Collado-Seidel V., et al. Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients. Sleep 2000, 23:597-602.
40. Lazzarini A., Walters A.S., Hickey K., et al. Studies of penetrance and anticipation in five autosomal-dominant restless legs syndrome pedigrees. Mov Disord 1999, 14:111-116.
41. Stefansson H., Rye D.B., Hicks A., et al. A genetic risk factor for periodic limb movements in sleep. N Engl J Med 2007, 357:639-647.
42. 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, 39:1000-1006.
43. Schormair B., Kemlink D., Roeske D., et al. PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome. Nat Genet 2008, 40:946-948.
44. Winkelmann J., Czamara D., Schormair B., et al. Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1. PLoS Genet 2011, 7:e1002171.
45. Freeman A.A., Rye D.B. The molecular basis of restless legs syndrome. Curr Opin Neurobiol 2013, 23:895-900.
46. Rizzo G., Manners D., Vetrugno R., et al. Combined brain voxel-based morphometry and diffusion tensor imaging study in idiopathic restless legs syndrome patients. Eur J Neurol 2012, 19:1045-1049.
47. Connor J.R., Ponnuru P., Lee B.Y., et al. Postmortem and imaging based analyses reveal CNS decreased myelination in restless legs syndrome. Sleep Med 2011, 12:614-619.
48. Hornyak M., Ahrendts J.C., Spiegelhalder K., et al. Voxel-based morphometry in unmedicated patients with restless legs syndrome. Sleep Med 2007, 9:22-26.
49. Margariti P.N., Astrakas L.G., Tsouli S.G., et al. Investigation of unmedicated early onset restless legs syndrome by voxel-based morphometry, T2 relaxometry, and functional MR imaging during the night-time hours. AJNR Am J Neuroradiol 2012, 33:667-672.
50. Astrakas L.G., Konitsiotis S., Margariti P., et al. T2 relaxometry and fMRI of the brain in late-onset restless legs syndrome. Neurology 2008, 71:911-916.
51. Allen R.P., Barker P.B., Wehrl F., et al. MRI measurement of brain iron in patients with restless legs syndrome. Neurology 2001, 56:263-265.
52. Rizzo G., Tonon C., Manners D., et al. Imaging brain functional and metabolic changes in restless legs syndrome. Curr Neurol Neurosci Rep 2013, 13:372.
53. Ku J., Cho Y.W., Lee Y.S., et al. Functional connectivity alternation of the thalamus in restless legs syndrome patients during the asymptomatic period: a resting-state connectivity study using functional magnetic resonance imaging. Sleep Med 2014, 15:289-294.
54. Earley C.J., Kuwabara H., Wong D.F., et al. Increased synaptic dopamine in the putamen in restless legs syndrome. Sleep 2013, 36:51-57.
55. Ekbom K.A. Restless legs 1945, Ivar Haeggströms, Stockholm.
56. Connor J.R., Ponnuru P., Wang X.S., et al. Profile of altered brain iron acquisition in restless legs syndrome. Brain 2011, 134:959-968.
57. Dusek P., Jankovic J., Le W. Iron dysregulation in movement disorders. Neurobiol Dis 2012, 46:1-18.
58. Earley C.J., Connor J.R., Beard J.L., et al. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 2000, 54:1698-1700.
59. Mizuno S., Mihara T., Miyaoka T., et al. CSF iron, ferritin and transferrin levels in restless legs syndrome. J Sleep Res 2005, 14:43-47.
60. Connor J.R., Boyer P.J., Menzies S.L., et al. Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology 2003, 61:304-309.
61. Earley C.J., Connor J.R., Beard J.L., et al. Ferritin levels in the cerebrospinal fluid and restless legs syndrome: effects of different clinical phenotypes. Sleep 2005, 28:1069-1075.
62. Unger E.L., Bianco L.E., Jones B.C., et al. Low brain iron effects and reversibility on striatal dopamine dynamics. Exp Neurol 2014, 261:462-468.
63. Ondo W.G., Hossain M.M., Gordon M.F., et al. Predictors of placebo response in restless legs syndrome studies. Neurology 2013, 81:193-194.
64. Fulda S., Wetter T.C. Where dopamine meets opioids: a meta-analysis of the placebo effect in restless legs syndrome treatment studies. Brain 2008, 131:902-917.
65. Comella C.L. Treatment of restless legs syndrome. Neurother 2014, 11:177-187.
66. Walters A.S., LeBrocq C., Dhar A., et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 2003, 4:121-132.
67. Kohnen R., Allen R.P., Benes H., et al. Assessment of restless legs syndrome-methodological approaches for use in practice and clinical trials. Mov Disord 2007, 22(Suppl. 18):S485-S494.
68. Allen R.P., Earley C.J. Validation of the Johns Hopkins restless legs severity scale. Sleep Med 2001, 2:239-242.
69. Hogl B., Gschliesser V. RLS assessment and sleep questionnaires in practice-lessons learned from Parkinson's disease. Sleep Med 2007, 8(Suppl. 2):S7-12.
70. Allen R., Oertel W., Walters A., et al. Relation of the International Restless Legs Syndrome Study Group rating scale with the Clinical Global Impression severity scale, the restless legs syndrome 6-item questionnaire, and the restless legs syndrome-quality of life questionnaire. Sleep Med 2013, 14:1375-1380.
71. Aukerman M.M., Aukerman D., Bayard M., et al. Exercise and restless legs syndrome: a randomized controlled trial. J Am Board Fam Med 2006, 19:487-493.
72. Buchfuhrer M.J. Strategies for the treatment of restless legs syndrome. Neurother 2012, 9:776-790.
73. Lettieri C.J., Eliasson A.H. Pneumatic compression devices are an effective therapy for restless legs syndrome: a prospective, randomized, double-blinded, sham-controlled trial. Chest 2009, 135:74-80.
74. Cui Y., Wang Y., Liu Z. Acupuncture for restless legs syndrome. Cochrane Database Syst Rev 2008, 4):CD006457.
75. Mitchell U.H., Myrer J.W., Johnson A.W., et al. Restless legs syndrome and near-infrared light: an alternative treatment option. Physiother Theory Pract 2011, 27:345-351.
76. Mitchell U.H. Nondrug-related aspect of treating Ekbom disease, formerly known as restless legs syndrome. Neuropsychiatr Dis Treat 2011, 7:251-257.
77. Wilt T.J., MacDonald R., Ouellette J., et al. Pharmacologic therapy for primary restless legs syndrome: a systematic review and meta-analysis. JAMA Intern Med 2013, 173:496-505.
78. Hornyak M., Trenkwalder C., Kohnen R., et al. Efficacy and safety of dopamine agonists in restless legs syndrome. Sleep Med 2012, 13:228-236.
79. Manconi M., Ferri R., Zucconi M., et al. Effects of acute dopamine-agonist treatment in restless legs syndrome on heart rate variability during sleep. Sleep Med 2011, 12:47-55.
80. Allen R.P., Ondo W.G., Ball E., et al. Restless legs syndrome (RLS) augmentation associated with dopamine agonist and levodopa usage in a community sample. Sleep Med 2011, 12:431-439.
81. Silver N., Allen R.P., Senerth J., et al. A 10-year, longitudinal assessment of dopamine agonists and methadone in the treatment of restless legs syndrome. Sleep Med 2011, 12:440-444.
82. Cornelius J.R., Tippmann-Peikert M., Slocumb N.L., et al. Impulse control disorders with the use of dopaminergic agents in restless legs syndrome: a case-control study. Sleep 2010, 33:81-87.
83. Tippmann-Peikert M., Park J.G., Boeve B.F., et al. Pathologic gambling in patients with restless legs syndrome treated with dopaminergic agonists. Neurology 2007, 68:301-303.
84. Garcia-Borreguero D., Hogl B., Ferini-Strambi L., et al. Systematic evaluation of augmentation during treatment with ropinirole in restless legs syndrome (Willis-Ekbom disease): results from a prospective, multicenter study over 66 weeks. Mov Disord 2012, 27:277-283.
85. 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, 75:92-97.
86. Walters A.S., Ondo W.G., 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, 19:1414-1423.
87. Allen R., Becker P.M., Bogan R., et al. Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome. Sleep 2004, 27:907-914.
88. Trenkwalder C., Hening W.A., Montagna P., et al. Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice. Mov Disord 2008, 23:2267-2302.
89. Garcia-Borreguero D., Kohnen R., Silber M.H., et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med 2013, 14:675-684.
90. Hogl B., Garcia-Borreguero D., Trenkwalder C., et al. Efficacy and augmentation during 6 months of double-blind pramipexole for restless legs syndrome. Sleep Med 2011, 12:351-360.
91. Partinen M., Hirvonen K., Jama L., et al. Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study-the PRELUDE study. Sleep Med 2006, 7:407-417.
92. Oertel W.H., Stiasny-Kolster K., Bergtholdt B., et al. Efficacy of pramipexole in restless legs syndrome: a six-week, multicenter, randomized, double-blind study (effect-RLS study). Mov Disord 2007, 22:213-219.
93. Silber M.H., Girish M., Izurieta R. Pramipexole in the management of restless legs syndrome: an extended study. Sleep 2003, 26:819-821.
94. Lipford M.C., Silber M.H. Long-term use of pramipexole in the management of restless legs syndrome. Sleep Med 2012, 13:1280-1285.
95. Allen R.P., Chen C., Garcia-Borreguero D., et al. Comparison of pregabalin with pramipexole for restless legs syndrome. N Engl J Med 2014, 370:621-631.
96. Quilici S., Abrams K.R., Nicolas A., et al. Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome. Sleep Med 2008, 9:715-726.
97. Stiasny-Kolster K., Kohnen R., Schollmayer E., et al. Patch application of the dopamine agonist rotigotine to patients with moderate to advanced stages of restless legs syndrome: a double-blind, placebo-controlled pilot study. Mov Disord 2004, 19:1432-1438.
98. Oertel W.H., Benes H., Garcia-Borreguero D., et al. One year open-label safety and efficacy trial with rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome. Sleep Med 2008, 9:865-873.
99. Hening W.A., Allen R.P., Ondo W.G., et al. Rotigotine improves restless legs syndrome: a 6-month randomized, double-blind, placebo-controlled trial in the United States. Mov Disord 2010, 25:1675-1683.
100. Oertel W.H., Benes H., Garcia-Borreguero D., et al. Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: a randomized, placebo-controlled polysomnographic study. Sleep Med 2010, 11:848-856.
101. Oertel W., Trenkwalder C., Benes H., et al. Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study. Lancet Neurol 2011, 10:710-720.
102. Kenney C., Jankovic J. Rotigotine transdermal patch in the treatment of Parkinson's disease and restless legs syndrome. Expert Opin Pharmacother 2007, 8:1329-1335.
103. Benes H., Garcia-Borreguero D., Ferini-Strambi L., et al. Augmentation in the treatment of restless legs syndrome with transdermal rotigotine. Sleep Med 2012, 13:589-597.
104. Inoue Y., Hirata K., Hayashida K., et al. Efficacy, safety and risk of augmentation of rotigotine for treating restless legs syndrome. Prog Neuropsychopharmacol Biol Psychiatry 2013, 40:326-333.
105. Hogl B., Oertel W.H., Schollmayer E., et al. Transdermal rotigotine for the perioperative management of restless legs syndrome. BMC Neurol 2012, 12:106.
106. Oertel W.H., Benes H., Bodenschatz R., et al. Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR). Neurology 2006, 67:1040-1046.
107. Trenkwalder C., Hundemer H.P., Lledo A., et al. Efficacy of pergolide in treatment of restless legs syndrome: the PEARLS Study. Neurology 2004, 62:1391-1397.
108. Tintner R., Manian P., Gauthier P., et al. Pleuropulmonary fibrosis after long-term treatment with the dopamine agonist pergolide for Parkinson Disease. Arch Neurol 2005, 62:1290-1295.
109. Andersohn F., Garbe E. Cardiac and noncardiac fibrotic reactions caused by ergot-and nonergot-derived dopamine agonists. Mov Disord 2009, 24:129-133.
110. Trenkwalder C., Stiasny K., Pollmacher T., et al. L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind, crossover trial. Sleep 1995, 18:681-688.
111. Trenkwalder C., Collado Seidel V., Kazenwadel J., et al. One-year treatment with standard and sustained-release levodopa: appropriate long-term treatment of restless legs syndrome?. Mov Disord 2003, 18:1184-1189.
112. von Scheele C., Kempi V. Long-term effect of dopaminergic drugs in restless legs. A 2-year follow-up. Arch Neurol 1990, 47:1223-1224.
113. Allen R.P., Earley C.J. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep 1996, 19:205-213.
114. Trenkwalder C., Benes H., Grote L., et al. Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial. Mov Disord 2007, 22:696-703.
115. Frauscher B., Gschliesser V., Brandauer E., et al. The severity range of restless legs syndrome (RLS) and augmentation in a prospective patient cohort: association with ferritin levels. Sleep Med 2009, 10:611-615.
116. Hendrich J., Van Minh A.T., Heblich F., et al. Pharmacological disruption of calcium channel trafficking by the alpha2delta ligand gabapentin. Proc Natl Acad Sci U S A 2008, 105:3628-3633.
117. Dooley D.J., Taylor C.P., Donevan S., et al. Ca2 + channel alpha2delta ligands: novel modulators of neurotransmission. Trends Pharmacol Sci 2007, 28:75-82.
118. Sills G.J. The mechanisms of action of gabapentin and pregabalin. Curr Opin Pharmacol 2006, 6:108-113.
119. Oertel W.H., Trenkwalder C., Zucconi M., et al. State of the art in restless legs syndrome therapy: practice recommendations for treating restless legs syndrome. Mov Disord 2007, 22(Suppl. 18):S466-S475.
120. Silber M.H., Ehrenberg B.L., Allen R.P., et al. An algorithm for the management of restless legs syndrome. Mayo Clin Proc 2004, 79:916-922.
121. Saletu M., Anderer P., Saletu-Zyhlarz G.M., et al. Comparative placebo-controlled polysomnographic and psychometric studies on the acute effects of gabapentin versus ropinirole in restless legs syndrome. J Neural Transm 2010, 117:463-473.
122. 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, 59:1573-1579.
123. Lal R., Sukbuntherng J., Luo W., et al. Pharmacokinetics and tolerability of single escalating doses of gabapentin enacarbil: a randomized-sequence, double-blind, placebo-controlled crossover study in healthy volunteers. Clin Ther 2009, 31:1776-1786.
124. Cundy K.C., Sastry S., Luo W., et al. Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin. J Clin Pharmacol 2008, 48:1378-1388.
125. Lal R., Ellenbogen A., Chen D., et al. A randomized, double-blind, placebo-controlled, dose-response study to assess the pharmacokinetics, efficacy, and safety of gabapentin enacarbil in subjects with restless legs syndrome. Clin Neuropharmacol 2012, 35:165-173.
126. Kushida C.A., Walters A.S., 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, 32:159-168.
127. Walters A.S., Ondo W.G., Kushida C.A., et al. Gabapentin enacarbil in restless legs syndrome: a phase 2b, 2-week, randomized, double-blind, placebo-controlled trial. Clin Neuropharmacol 2009, 32:311-320.
128. Bogan R.K., Bornemann M.A., Kushida C.A., Barrett R.W., et al. Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study. Mayo Clin Proc 2010, 85:512-521.
129. Ellenbogen A.L., Thein S.G., Winslow D.H., et al. A 52-week study of gabapentin enacarbil in restless legs syndrome. Clin Neuropharmacol 2011, 34:8-16.
130. Lee D.O., Ziman R.B., Perkins A.T., et al. 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 Med 2011, 7:282-292.
131. Winkelman J.W., Bogan R.K., Schmidt M.H., et al. Randomized polysomnography study of gabapentin enacarbil in subjects with restless legs syndrome. Mov Disord 2011, 26:2065-2072.
132. Inoue Y., Uchimura N., Kuroda K., et al. Long-term efficacy and safety of gabapentin enacarbil in Japanese restless legs syndrome patients. Prog Neuropsychopharmacol Biol Psychiatry 2012, 36:251-257.
133. Garcia-Borreguero D., Ferini-Strambi L., Kohnen R., et al. European guidelines on management of restless legs syndrome: report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society. Eur J Neurol 2012, 19:1385-1396.
134. XenoPort I Gabapentin Enacarbil (GSK1838262) Adult Restless Legs Syndrome Post Marketing commitment study (CONCORD) accessed 06.01.14. http://clinicaltrials.gov/ct2/show/NCT01668667?term=concord%26rank=1.
135. Kume A. Gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (Willis-Ekbom disease): 600 or 1,200 mg dose?. Neuropsychiatr Dis Treat 2014, 10:249-262.
136. Sommer M., Bachmann C.G., Liebetanz K.M., et al. Pregabalin in restless legs syndrome with and without neuropathic pain. Acta Neurol Scand 2007, 115:347-350.
137. Garcia-Borreguero D., Larrosa O., Williams A.M., et al. Treatment of restless legs syndrome with pregabalin: a double-blind, placebo-controlled study. Neurology 2010, 74:1897-1904.
138. Allen R., Chen C., Soaita A., et al. A randomized, double-blind, 6-week, dose-ranging study of pregabalin in patients with restless legs syndrome. Sleep Med 2010, 11:512-519.
139. Chokroverty S. Therapeutic dilemma for restless legs syndrome. N Engl J Med 2014, 370:667-668.
140. Benarroch E.E. Endogenous opioid systems: current concepts and clinical correlations. Neurology 2012, 79:807-814.
141. Trenkwalder C., Benes H., Grote L., et al. Prolonged release oxycodone-naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebo-controlled trial with an open-label extension. Lancet Neurol 2013, 12:1141-1150.
142. von Spiczak S., Whone A.L., Hammers A., et al. The role of opioids in restless legs syndrome: an [11C]diprenorphine PET study. Brain 2005, 128:906-917.
143. Walters A.S., Ondo W.G., Zhu W., et al. Does the endogenous opiate system play a role in the Restless Legs Syndrome? A pilot post-mortem study. J Neurol Sci 2009, 279:62-65.
144. Vetrugno R., La Morgia C., D'Angelo R., et al. Augmentation of restless legs syndrome with long-term tramadol treatment. Mov Disord 2007, 22:424-427.
145. Earley C.J., Allen R.P. Restless legs syndrome augmentation associated with tramadol. Sleep Med 2006, 7:592-593.
146. Walters A.S., Wagner M.L., Hening W.A., et al. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep 1993, 16:327-332.
147. Kaplan P.W., Allen R.P., Buchholz D.W., et al. A double-blind, placebo-controlled study of the treatment of periodic limb movements in sleep using carbidopa/levodopa and propoxyphene. Sleep 1993, 16:717-723.
148. Walters A.S., Winkelmann J., Trenkwalder C., et al. Long-term follow-up on restless legs syndrome patients treated with opioids. Mov Disord 2001, 16:1105-1109.
149. Ondo W.G. Methadone for refractory restless legs syndrome. Mov Disord 2005, 20:345-348.
150. Wang J., O'Reilly B., Venkataraman R., et al. Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: a randomized, double-blind, placebo-controlled study. Sleep Med 2009, 10:973-975.
151. Davis B.J., Rajput A., Rajput M.L., et al. A randomized, double-blind placebo-controlled trial of iron in restless legs syndrome. Eur Neurol 2000, 43:70-75.
152. Trenkwalder C., Hogl B., Benes H., et al. Augmentation in restless legs syndrome is associated with low ferritin. Sleep Med 2008, 9:572-574.
153. Earley C.J., Heckler D., Allen R.P. The treatment of restless legs syndrome with intravenous iron dextran. Sleep Med 2004, 5:231-235.
154. Ondo W.G. Intravenous iron dextran for severe refractory restless legs syndrome. Sleep Med 2010, 11:494-496.
155. Grote L., Leissner L., Hedner J., et al. A randomized, double-blind, placebo controlled, multi-center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome. Mov Disord 2009, 24:1445-1452.
156. Allen R.P., Adler C.H., Du W., et al. Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. Sleep Med 2011, 12:906-913.
157. Cho Y.W., Allen R.P., Earley C.J. Lower molecular weight intravenous iron dextran for restless legs syndrome. Sleep Med 2013, 14:274-277.
158. Silverstein S.B., Rodgers G.M. Parenteral iron therapy options. Am J Hematol 2004, 76:74-78.
159. Garcia-Borreguero D., Allen R.P., Kohnen R., et al. 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 2007, 8:520-530.
160. Allen R.P., Ondo W.G., Ball E., et al. Restless legs syndrome (RLS) augmentation associated with dopamine agonist and levodopa usage in a community sample. Sleep Med 2011, 12:431-439.
161. Garcia-Borreguero D., Allen R., Kohnen R., et al. Loss of response during long-term treatment of restless legs syndrome: guidelines approved by the International Restless Legs Syndrome Study Group for use in clinical trials. Sleep Med 2010, 11:956-957.
162. Guilleminault C., Cetel M., Philip P. Dopaminergic treatment of restless legs and rebound phenomenon. Neurology 1993, 43:445.
163. Page R.L., Ruscin J.M., Bainbridge J.L., et al. Restless legs syndrome induced by escitalopram: case report and review of the literature. Pharmacotherapy 2008, 28:271-280.
164. Ohayon M.M., Roth T. Prevalence of restless legs syndrome and periodic limb movement disorder in the general population. J Psychosom Res 2002, 53:547-554.
165. Rottach K.G., Schaner B.M., Kirch M.H., et al. Restless legs syndrome as side effect of second generation antidepressants. J Psychiatr Res 2008, 43:70-75.
166. Salin-Pascual R.J., Galicia-Polo L., Drucker-Colin R. Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers. J Clin Psychiatry 1997, 58:348-350.
167. Goerke M., Rodenbeck A., Cohrs S., et al. The influence of the tricyclic antidepressant amitriptyline on periodic limb movements during sleep. Pharmacopsychiatry 2013, 46:108-113.
168. Hoque R., Chesson A.L. Pharmacologically induced/exacerbated restless legs syndrome, periodic limb movements of sleep, and REM behavior disorder/REM sleep without atonia: literature review, qualitative scoring, and comparative analysis. J Clin Sleep Med 2010, 6:79-83.
169. Smith H.S., Dhingra R., Ryckewaert L., et al. Proton pump inhibitors and pain. Pain Physician 2009, 12:1013-1023.
170. Alvarez-Ossorio L., Kirchner H., Kluter H., et al. Low ferritin levels indicate the need for iron supplementation: strategy to minimize iron-depletion in regular blood donors. Transfus Med 2000, 10:107-112.
171. Rizzo G., Manners D., Testa C., et al. Low brain iron content in idiopathic restless legs syndrome patients detected by phase imaging. Mov Disord 2013, 28:1886-1890.
172. Allen R.P., Auerbach S., Bahrain H., et al. The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia. Am J Hematol 2013, 88:261-264.
173. Montplaisir J., Boucher S., Nicolas A., et al. Immobilization tests and periodic leg movements in sleep for the diagnosis of restless leg syndrome. Mov Disord 1998, 13:324-329.
174. Garcia-Borreguero D., Kohnen R., Boothby L., et al. Validation of the Multiple Suggested Immobilization Test: A Test for the Assessment of Severity of Restless Legs Syndrome (Willis-Ekbom Disease). Sleep 2013, 36:1101-1109.
175. Ferini-Strambi L., Marelli S. Pharmacotherapy for restless legs syndrome. Expert Opin Pharmacother 2014, 15:1127-1138.
176. Garcia-Borreguero D., Allen R.P., Benes H., et al. Augmentation as a treatment complication of restless legs syndrome: concept and management. Mov Disord 2007, 22(Suppl. 18):S476-S484.
177. Maestri M., Fulda S., Ferini-Strambi L., et al. Polysomnographic record and successful management of augmentation in restless legs syndrome/Willis-Ekbom disease. Sleep Med 2014, 15:570-575.
178. Kurlan R., Rabin M. Augmentation in restless legs syndrome: poor response to sudden withdrawal of dopaminergic therapy. J Parkinsonism Restless Legs Syndr 2013, 3:49-52.
179. Kurlan R., Richard I.H., Deeley C. Medication tolerance and augmentation in restless legs syndrome: the need for drug class rotation. J Gen Intern Med 2006, 21:C1-C4.
180. Ondo W.G. Restless legs syndrome: pathophysiology and treatment. Curr Treat Options Neurol 2014, 16:317.
181. Sivertsen B., Omvik S., Pallesen S., et al. Cognitive behavioral therapy vs zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial. JAMA 2006, 295:2851-2858.
182. Williams J., Roth A., Vatthauer K., et al. Cognitive behavioral treatment of insomnia. Chest 2013, 143:554-565.
183. Buysse D.J. Insomnia. JAMA 2013, 309:706-716.
184. Jama L., Hirvonen K., Partinen M., et al. A dose-ranging study of pramipexole for the symptomatic treatment of restless legs syndrome: polysomnographic evaluation of periodic leg movements and sleep disturbance. Sleep Med 2009, 10:630-636.
185. Bogan R.K., Fry J.M., Schmidt M.H., 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, 81:17-27.
186. Happe S., Sauter C., Klosch G., et al. Gabapentin versus ropinirole in the treatment of idiopathic restless legs syndrome. Neuropsychobiology 2003, 48:82-86.
187. Saletu M., Anderer P., Saletu-Zyhlarz G., et al. Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol 2001, 11:153-161.
188. Ross D.A., Narus M.S., Nutt J.G. Control of medically refractory restless legs syndrome with intrathecal morphine: case report. Neurosurgery 2008, 62:E263. Discussion E.
189. Lindvall P., Ruuth K., Jakobsson B., et al. Intrathecal morphine as a treatment for refractory restless legs syndrome. Neurosurgery 2008, 63:E1209. Author reply E.
190. Jakobsson B., Ruuth K. Successful treatment of restless legs syndrome with an implanted pump for intrathecal drug delivery. Acta Anaesthesiol Scand 2002, 46:114-117.
191. Lindvall P.K., Ruuth K., Jakobsson B., et al. Intrathecal morphine infusion a possible treatment in restless legs]. Lakartidningen 2007, 104:2250-2252.
192. Lindvall P., Hariz G.M., Blomstedt P. Overall self-perceived health in Restless legs treated with intrathecal morphine. Acta Neurol Scand 2013, 127:268-273.
193. Hornyak M., Kaube H. Long-Term treatment of a patient with severe restless legs syndrome using intrathecal morphine. Neurology 2012, 79:2361-2362.
194. Ondo W.G., Jankovic J., Simpson R., et al. Globus pallidus deep brain stimulation for refractory idiopathic restless legs syndrome. Sleep Med 2012, 13:1202-1204.
195. Okun M.S., Fernandez H.H., Foote K.D. Deep brain stimulation of the GPi treats restless legs syndrome associated with dystonia. Mov Disord 2005, 20:500-501.
196. Rye D.B., DeLong M.R. Amelioration of sensory limb discomfort of restless legs syndrome by pallidotomy. Ann Neurol 1999, 46:800-801.
197. Kedia S., Moro E., Tagliati M., et al. Emergence of restless legs syndrome during subthalamic stimulation for Parkinson disease. Neurology 2004, 63:2410-2412.
198. Driver-Dunckley E., Evidente V.G., Adler C.H., et al. Restless legs syndrome in Parkinson's disease patients may improve with subthalamic stimulation. Mov Disord 2006, 21:1287-1289.
199. Ondo W. VIM deep brain stimulation does not improve pre-existing restless legs syndrome in patients with essential tremor. Parkinsonism Relat Disord 2006, 12:113-114.
200. Srivanitchapoom P., Pandey S., Hallett M. Restless legs syndrome and pregnancy: A review. Parkinsonism Relat Disord 2014, 20:716-722.
201. Manconi M., Ferini-Strambi L. Restless legs syndrome among pregnant women. Sleep 2004, 27:350. Author reply 1.
202. Patrick L.R. Restless legs syndrome: pathophysiology and the role of iron and folate. Altern Med Rev 2007, 12:101-112.
203. Picchietti D.L., Bruni O., de Weerd A., et al. Pediatric restless legs syndrome diagnostic criteria: an update by the International Restless Legs Syndrome Study Group. Sleep Med 2013, 14:1253-1259.
204. Picchietti D., Allen R.P., Walters A.S., et al. Restless legs syndrome: prevalence and impact in children and adolescents - the Peds REST study. Pediatrics 2007, 120:253-266.
205. Wagner M.L., Walters A.S., Fisher B.C. Symptoms of attention-deficit/hyperactivity disorder in adults with restless legs syndrome. Sleep 2004, 27:1499-1504.
206. Oner P., Dirik E.B., Taner Y., et al. Association between low serum ferritin and restless legs syndrome in patients with attention deficit hyperactivity disorder. Tohoku J Exp Med 2007, 213:269-276.
207. Silvestri R., Gagliano A., Arico I., et al. Sleep disorders in children with Attention-Deficit/Hyperactivity Disorder (ADHD) recorded overnight by video-polysomnography. Sleep Med 2009, 10:1132-1138.
208. Newcorn J.H., Schulz K., Harrison M., et al. Alpha 2 adrenergic agonists. Neurochemistry, efficacy, and clinical guidelines for use in children. Pediatr Clin North Am 1998, 45. 1099-22, viii.
209. Owens J.A., Rosen C.L., Mindell J.A. Medication use in the treatment of pediatric insomnia: results of a survey of community-based pediatricians. Pediatrics 2003, 111:e628-e635.
210. Picchietti M.A., Picchietti D.L. Advances in pediatric restless legs syndrome: iron, genetics, diagnosis and treatment. Sleep Med 2010, 11:643-651.
211. Kotagal S., Silber M.H. Childhood-onset restless legs syndrome. Ann Neurol 2004, 56:803-807.
212. Muhle H., Neumann A., Lohmann-Hedrich K., et al. Childhood-onset restless legs syndrome: clinical and genetic features of 22 families. Mov Disord 2008, 23:1113-1121. quiz 203.
213. Konofal E., Arnulf I., Lecendreux M., et al. Ropinirole in a child with attention-deficit hyperactivity disorder and restless legs syndrome. Pediatr Neurol 2005, 32:350-351.
214. Walters A.S., Mandelbaum D.E., Lewin D.S., et al. Dopaminergic therapy in children with restless legs/periodic limb movements in sleep and ADHD. Dopaminergic Therapy Study Group. Pediatr Neurol 2000, 22:182-186.
215. Tilma J., Tilma K., Norregaard O., et al. Early childhood-onset restless legs syndrome: symptoms and effect of oral iron treatment. Acta Paediatr 2013, 102:e221-e226.
216. Dosman C., Witmans M., Zwaigenbaum L. Iron's role in paediatric restless legs syndrome - a review. Paediatr Child Health 2012, 17:193-197.
217. Grim K., Lee B., Sung A.Y., et al. Treatment of childhood-onset restless legs syndrome and periodic limb movement disorder using intravenous iron sucrose. Sleep Med 2013, 14:1100-1104.