Sleep Medicine Reviews
Volume 6, Issue 4 , Pages 253-265 , July 2002

Clinical symptomatology and treatment of restless legs syndrome and periodic limb movement disorder

  • Karin Stiasny

      Affiliations

    • Department of Neurology, Center of Nervous Diseases, Philipps University of Marburg, Germany
    • ,
  • Wolfgang Hermann Oertel

      Affiliations

    • Department of Neurology, Center of Nervous Diseases, Philipps University of Marburg, Germany
    • ,
  • Claudia Trenkwalder

      Affiliations

    • Department of Clinical Neurophysiology, University of Göttingen, Germany

References 

  1. Walters AS. Toward a better definition of the restless legs syndrome. The International Restless Legs Syndrome Study Group. Mov Disord. 1995;10:634–642
  2. Hening WA, Walters A, LeBroca C, Hirsch L, Dhar A, IRLSSG Mot . The International RLS Study Group Rating Scale: a reliable and valid instrument for assessing severity of the restless legs syndrome. Neurology. 2001;56:A4
  3. Wetter TC, Stiasny K, Winkelmann J, Buhlinger A, Brandenburg U, Penzel T. A randomized controlled study of pergolide in patients with restless legs syndrome. Neurology. 1999;52:944–950
  4. Stiasny K, Wetter T, Winkelmann J, Brandenburg U, Penzel T, Rubin S. Long-term effects of pergolide in the treatment of restless legs syndrome. Neurology. 2001;
  5. Trenkwalder C, Brandenburg U, Hundemer H-P, Lledo A, Quail D, Swieca J. A randomized long-term placebo-controlled multicenter trial of pergolide in the treatment of RLS – the PEARLS-Study. Neurology (abstract). 2001;
  6. Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, Lesperance P. 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
  7. Smith RC. Relationship of periodic movements in sleep (nocturnal myoclonus) and the babinski sign. Sleep. 1985;8:239–243
  8. Sleep. 1993;16:748–759
  9. Atlas Task Force of the American Sleep Disorders Association (ASDA), The International Classification of Sleep Disorders – Diagnostic and Coding Manual, Rochester, Minnesota, 1997
  10. Sleep. 1992;15:173–184
  11. Pollmächer T, Schulz H. Periodic leg movements (PLM): their relationship to sleep stages. Sleep. 1993;16:572–577
  12. Ancoli-Israel S, Kripke DF, Klauber MR, Mason WJ, Fell R, Kaplan O. Periodic limb movements in sleep in community-dwelling elderly. Sleep. 1991;14:496–500
  13. Bixler EO, Kales A, Vela-Bueno A, Jacoby JA, S S, Soldatos CR. Nocturnal myoclonus and nocturnal myoclonic activity in a normal population. Research Communications in Chemical Pathology and Pharmacology. 1982;36:129–140
  14. Dickel, MJ, Mosko, SS, Morbidity cut-offs for sleep apnea and periodic leg movements in predicting subjective complaints in seniors, 1990, 13, 155, 166
  15. Mendelson WB. Are periodic leg movements associated with clinical sleep disturbances?. Sleep. 1996;19:219–223
  16. Schenck CH, Mahowald MW. Motor dyscontrol in narcolepsy: Rapid-eye-movement (REM) sleep without atonia and REM sleep behavior disorder. Ann Neurol. 1992;32:3–10
  17. Guilleminault C, Philip P. Tiredness and somnolence despite initial treatment of obstructive sleep apnea syndrome (what to do when an OSAS patient stays hypersomnolent despite treatment). Sleep. 1996;19:S117–122
  18. Lapierre O, Montplaisir J. Polysomnographic features of REM sleep behavior disorder: development of a scoring method. Neurology. 1992;42:1371–1374
  19. Askenasy JJM. Sleep in Parkinson`s disease. Acta Neurol Scand. 1993;87:167–170
  20. Gadot N, Costeff H, Harel S, Lavie P. Motor abnormalities during sleep in patients with childhood hereditary progressive dystonia, and their uneffected family members. Sleep. 1989;12:233–238
  21. Wetter TC, Collado-Seidel V, Pollmächer T, Yassoudris A, Trenkwalder C. Sleep and periodic leg movement patterns in drug-free patients with Parkinson's disease and Multiple System Atrophy. Sleep. 2000;23:361–367
  22. Ferrini-Strambi L, Filippi M, Martinelli V, Oldani A, Rovaris M, Zucconi M. Nocturnal sleep study in multiple sclerosis: correlations with clinical and brain magnetic resonance imaging findings. J Neurol Sci. 1994;125:194–197
  23. Walters AS, Wagner M, Hening WA. Periodic limb movements as the initial manifestation of restless legs syndrome triggered by lumbosacral radiculopathy [letter]. Sleep. 1996;19:825–826
  24. de Mello MT, Silva AC, Rueda AD, Poyares D, Tufik S. Correlation between K complex, periodic leg movements (PLM), and myoclonus during sleep in paraplegic adults before and after an acute physical activity. Spinal Cord. 1997;35:248–252
  25. Lee MS, Choi YC, Lee SH, Lee SB. Sleep-related periodic leg movements associated with spinal cord lesions. Mov Disord. 1996;11:719–722
  26. Walker SL, Fine A, Kryger MH. L-DOPA/carbidopa for nocturnal movement disorders in uremia. Sleep. 1996;19:214–218
  27. Culpepper WJ, P . B, Shaffer JI. Time-of-night patterns in PLMS activity. Sleep. 1992;15:306–311
  28. Phillips B, Young T, Finn L, Asher K, Hening WA, Purvis C. Epidemiology of Restless Legs Syndrome in Adults. Arch Intern Med. 2000;160:2137–2141
  29. Rothdach A, Trenkwalder C, Haberstock J, Keil U, Berger K. Prevalence and risk factors of RLS in an elderly population – The MEMO study. Neurology. 2000;52:1064–1068
  30. Lavigne GJ, Montplaisir JY. Restless legs syndrome and sleep bruxism: prevalence and association among Canadians. Sleep. 1994;17:739–743
  31. Walters AS, Hickey K, Maltzman J, Verrico T, Joseph D, Hening W. A questionnaire study of 138 patients with restless legs syndrome: the “Night-Walkers” survey. Neurology. 1996;46:92–95
  32. Walters AS, Picchietti DL, Ehrenberg BL, Wagner ML. Restless legs syndrome in childhood and adolescence. Pediatr Neurol. 1994;11:241–245
  33. Winkelmann J, Wetter TC, Collado-Seidel V, Gasser T, Dichgans M, Yassouridis A. Frequency and characteristics of the hereditary restless legs syndrome in a population of 300 patients. Sleep. 2000;23:597–602
  34. Trenkwalder C, Seidel VC, Gasser T, Oertel WH. Clinical symptoms and possible anticipation in a large kindred of familial restless legs syndrome. Mov Disord. 1996;11:389–394
  35. Stautner A, Stiasny K, Collado-Seidel V, Bucher SF, Oertel WH, Trenkwalder C. Comparison of idiopathic and uremic restless legs syndrome: results of a database of 134 patients. Mov Dis. 1996;11:98
  36. Ondo W, Jankovic J. Restless legs syndrome: clinicoetiologic correlates. Neurology. 1996;47:1435–1441
  37. Lazzarini A, Walters AS, Hickey K, Coccagna G, Lugaresi E, Ehrenberg BL. Studies of penetrance and anticipation in five autosomal-dominant restless legs syndrome pedigrees. Mov Disord. 1999;14:111–116
  38. Collado-Seidel V, Kohnen R, Samtleben W, Hillebrand GF, Oertel WH, Trenkwalder C. Clinical and biochemical findings in uremic patients with and without restless legs syndrome. Am J Kidney Dis. 1998;31:324–328
  39. O'Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing. 1994;23:200–203
  40. 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;33:60–63
  41. McParland P, Pearce JM. Restless legs syndrome in pregnancy. Case reports. Clin Exp Obstet Gynecol. 1990;17:5–6
  42. Winkelmann J, Wetter TC, Trenkwalder C, Auer D. Periodic limb movements in Syringomyelia and Syringobulbia. Mov Disord. 2000;15:752–755
  43. Rutkove SB, Matheson JK, Logigian EL. Restless legs syndrome in patients with polyneuropathy. Muscle Nerve. 1996;19:670–672
  44. Iannaccone S, Zucconi M, Marchettini P, Ferini-Strambi L, Nemni R, Quattrini A. Evidence of peripheral axonal neuropathy in primary restless legs syndrome. Mov Disord. 1995;10:2–9
  45. Gemignani F, Marbini A, Di Giovanni G, Salih S, Terzano MG. Charcot-Marie-Tooth disease type 2 with restless legs syndrome. Neurology. 1999;52:1064–1066
  46. Walters AS, Mandelbaum DE, Lewin DS, Kugler S, England SJ, Miller M. Dopaminergic therapy in children with restless legs/periodic limb movements in sleep and ADHD. Pediatric Neurology. 2000;22:182–186
  47. Picchietti DL, England SJ, Walters AS, Willis K, Verrico T. Periodic limb movement disorder and restless legs syndrome in children with attention-deficit hyperactivity disorder. J Child Neurol. 1998;13:588–594
  48. Dressler D, Thompson PD, Gledhill RF, Marsden CD. The syndrome of painful legs and moving toes. Mov Disord. 1994;9:13–21
  49. Sleep. 1997;20:406–422
  50. Montplaisir J, Boucher S, Nicolas A, Lesperance P, Gosselin A, Rompre P. Immobilization tests and periodic leg movements in sleep for the diagnosis of restless leg syndrome. Mov Disord. 1998;13:324–329
  51. Michaud M, Soucy JP, Chabli A, Lavigne G, Montplaisir J. Spect imaging of pre- and postsynaptic dopaminergic functions in patients with restless legs syndrome. Sleep. 2000;23:A129
  52. Staedt J, Stoppe G, Kogler A, Riemann H, Hajak G, Munz DL. Nocturnal myoclonus syndrome (periodic movements in sleep) related to central dopamine D2-receptor alteration. Eur Arch Psychiatry Clin Neurosci. 1995;245:8–10
  53. Turjanski N, Lees AJ, Brooks DJ. Striatal dopaminergic function in restless legs syndrome – 18F-dopa and 11C-raclopride PET studies. Neurology. 1999;52:932–937
  54. Ruottinen HM, Partinen M, Hublin M, Bergmann J, Haaparanta M, Solin O. A F-DOPA PET study in patients with periodic limb movement disorder and restless legs syndrome. Neurology. 2000;54:502–504
  55. Trenkwalder C, Walters AS, Hening WA, Chokroverty S, Antonini A, Dhawan V. Positron Emission Tomographic Studies in Restless Legs Syndrome. Mov Disord. 1999;14:141–145
  56. San Pedro EC, Mountz JM, Mountz JD, Liu HG, Katholi CR, Deutsch G. Familial painful restless legs syndrome correlates with pain dependent variation of blood flow to the caudate, thalamus, and anterior cingulate gyrus. J Rheumatol. 1998;25:2270–2275
  57. Bucher SF, Seelos KC, Oertel WH, Reiser M, Trenkwalder C. Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann Neurol. 1997;41:639–645
  58. Trenkwalder C, Bucher SF, Oertel WH, Proeckl D, Plendl H, Paulus W. Bereitschaftspotential in idiopathic and symptomatic restless legs syndrome. Electroencephalogr Clin Neurophysiol. 1993;89:95–103
  59. Stiasny K, Haeske H, Müller H-H, Braune H-J, Oertel WH. Inhibition of motor circuits is impaired in restless legs syndrome. Mov Disord. 2000;15:80
  60. Entezari-Taher M, Singleton JR, Jones CR, Meekins G, Petajan JH, Smith AG. Changes in excitability of motor cortical circuitry in primary restless legs syndrome [In Process Citation]. Neurology. 1999;53:1201–1205
  61. Tergau F, Wischer S, Paulus W. Impaired motor cortex excitability in patients with restless legs syndrome. Neurology. 1998;50:A 223
  62. Bara-Jimenez W, Aksu M, Graham B, Sato S, Hallet M. Periodic limb movements in sleep. State-dependent excitability of the spinal flexor reflex. Neurology. 2000;54:1609–1615
  63. Tarquini B. Iron metabolism: clinical chronobiological aspects. Chronobiologica. 1978;5:315–336
  64. Early CJ, Connors JR, Allen RP. RLS patients have abnormal reduced CSF ferritin compared to normal controls. Neurology. 1999;52:A111–A112
  65. Allen RP, Barker PB, Wehrl F, Song HK, Early CJ. MRI measurement of brain iron in patients with restless legs syndrome. Neurology. 2001;56:263–265
  66. Davis BJ, Rajput A, Rajput ML, Aul EA, Eichhorn GR. A randomized, double-blind, placebo-controlled trial of iron in restless legs syndrome. Eur Neurol. 2000;43:70–75
  67. Hornyak M, Voderholzer U, Hohagen F, Berger M, Riemann D. Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study. Sleep. 1998;21:501–505
  68. Chesson AL, Wise M, Davila D, Johnson S, Littner M, Anderson M. Practice parameters for the treatment of restless legs syndrome and periodic limb movement disorder. Sleep. 1999;22:961–968
  69. Hening W, Allen R, Earley C, Kushida C, Picchietti D, Silber M. The treatment of restless legs syndrome and periodic limb movement disorder – an American Academy of Sleep Medicine Review. Sleep. 1999;22:970–998
  70. Trenkwalder C, Stiasny K, Pollmächer T, Wetter TC, Schwarz J, Kohnen R. L-dopa therapy of uremic and idiopathic restless legs syndrome: A double-blind, crossover trial. Sleep. 1995;18:681–688
  71. Collado-Seidel V, Kazenwadel J, Wetter TC, Kohnen R, Winkelmann J, Selzer R. A controlled study of additional SR-L-dopa in L-dopa responsive RLS with late night symptoms. Neurology. 1999;52:285–290
  72. Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep. 1996;19:205–213
  73. Walters AS, Hening WA, Kavey N, Chokroverty S, Gidro-Frank S. A double-blind randomized crossover trial of bromocriptine and placebo in restless legs syndrome. Ann Neurol. 1988;24:455–458
  74. Stiasny K, Roebbecke J, Schüler P, Oertel WH. Treatment of idiopathic restless legs syndrome (RLS) with the D2-agonist cabergoline – an open clinical trial. Sleep. 2000;23:349–354
  75. Saletu B, Gruber G, Saletu M, Brandstatter N, Hauer C, Prause W. Sleep laboratory studies in restless legs syndrome patients as compared with normals and acute effects of ropinirole. 1. Findings on objective and subjective sleep and awakening quality. Sleep Neuropsychobiology. 2000;41:181–189
  76. Montplaisir J, Nicolas A, Denesle R, Gomez-Mancilla B. Restless legs syndrome improved by pramipexole: a double-blind randomized trial. Neurology. 1999;52:938–943
  77. Montplaisir J, Denesle R, Petit D. Pramipexole in the treatment of restless legs syndrome: a follow-up study. European J of Neurol. 2000;7:27–31
  78. Stiasny K, Moeller JC, Oertel WH. Safety of pramipexole in patients with restless legs syndrome. Neurology. 2000;55:1589–1590
  79. Benes H, Deißler A, Clarenbach P, Rodenbeck A, Hajak G. Lisurid in the management of restless legs syndrome – an extended polysomnographic study. Mov Disord. 2000;15:134
  80. Tergau F, Wischer S, Wolf C, Paulus W. Treatment of restless legs syndrome with α-dihydroergocriptine. Mov Disord. 1998;13:292
  81. Evidente VGH, Adler CH, Caviness JN, Hentz JG, Gwinn-Hardy K. Amantadine is beneficial in restless legs syndrome. Mov Disord. 2000;15:324–327
  82. Reuter I, Ellis CM, Chauduri KR. Nocturnal subcutaneous apomorphine infusion in Parkinson's disease and restless legs syndrome. Acta Neurol Scand. 1999;100:163–167
  83. Walters AS, Wagner ML, Hening WA, Grasing K, Mills R, Chokroverty S. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep. 1993;16:327–332
  84. Allen RP, Kaplan PW, Buchholz DW, Early CJ, Walters JK. Double-blinded, placebo controlled comparison of high dose propoxyphene and moderate dose carbidopa/levodopa for treatment of periodic limb movements in sleep. Sleep Res. 1992;21:166
  85. Lauerma H, Markkula J. Treatment of restless legs syndrome with tramadol: an open study. J Clin Psychiatry. 1999;60:241–244
  86. Walters AS, Winkelmann J, Trenkwalder C, Fry JM, Kataria V, Wagner M. Long-term opioid monotherapy in patients with restless legs syndrome. Mov Disord. 2001;
  87. Telstad W, Sorensen O, Larsen S, Lillevold PE, Stensrud P, Nyberg-Hansen R. Treatment of the restless legs syndrome with carbamazepine: a double blind study. Br Med J (Clin Res Ed). 1984;288:444–446
  88. Zucconi M, Coccagna G, Petronelli R, Gerardi R, Mondini S, Cirignotta F. Nocturnal myoclonus in restless legs syndrome effect of carbamazepine treatment. Funct Neurol. 1989;4:263–271
  89. Laschewski F, Sanner B, Konermann M, Kreuzer I, Horstensmeyer D, Sturm A. Pronounced hypersomnia in a 13-year-old patient with periodic leg movements]. Pneumologie. 1997;51:725–728
  90. Ehrenberg BL, Eisensehr I, Corbett KE, Crowley PF, Walters AS. Valproate for sleep consolidation in periodic limb movement disorder. J Clin Psychopharmacol. 2000;20:574–578
  91. Adler CH. Treatment of restless legs syndrome with gabapentin. Clin Neuropharmacol. 1997;20:148–151
  92. Peled R, Lavie P. Double-blind evaluation of clonazepam on periodic leg movements in sleep. J Neurol Neurosurg Psychiatry. 1987;50:1679–1681
  93. Horiguchi J, Inami Y, Sasaki A, Nishimatsu O, Sukegawa T. Periodic leg movements in sleep with restless legs syndrome: effect of clonazepam treatment. Jpn J Psychiatry Neurol. 1992;46:727–732
  94. Braude W, Barnes T. Clonazepam: effective treatment for restless legs syndrome in uraemia [letter]. Br Med J (Clin Res Ed). 1982;284:510
  95. Montagna P, Sassoli de Bianchi L, Zucconi M, Cirignotta F, Lugaresi E. Clonazepam and vibration in restless legs syndrome. Acta Neurol Scand. 1984;69:428–430
  96. Guilleminault C, Flagg W. Effect of baclofen on sleep-related periodic leg movements. Ann Neurol. 1984;15:234–239
  97. Wagner ML, Walters AS, Coleman RG, Hening WA, Grasing K, Chokroverty S. Randomized, double-blind, placebo-controlled study of clonidine in restless legs syndrome. Sleep. 1996;19:52–58
  98. Trenkwalder C, Brandenburg U, Hundemer HP, Lledo A, Quail D, Wood E, et al. A randomized long-term placebo-controlled multicenter trial of pergolide in the treatment of restless legs syndrome with central evaluation of polysomnographic data. Neurology. 2001;56:A5

PII: S1087-0792(01)90193-5

doi: 10.1053/smrv.2001.0193

Sleep Medicine Reviews
Volume 6, Issue 4 , Pages 253-265 , July 2002

Article Tools