Restless Legs Syndrome

Authors: D. Kemlink;  J. Vávrová
Authors place of work: Neurologická klinika 1. LF UK a VFN v Praze
Published in the journal: Cesk Slov Neurol N 2011; 74/107(2): 141-149
Category: Minimonografie


Restless legs syndrome (RLS) is a common neurological disorder with a prevalence in Europe ranging from 5% to 10%. The disease is characterized by an imperative urge to move the legs associated with an unpleasant sensation in the lower limbs, typically occurring at rest in the evening and during the night. RLS can lead to disturbances of sleep and an impaired quality of life. It is diagnosed clinically by means of four internationally recognized criteria that summarize the main characteristics of the disorder. The disease exists in forms classified as idiopathic and secondary. Iron deficiency, end-stage renal disease and pregnancy are well established secondary causes of RLS. Several neurological disorders are also associated with RLS. Iron and dopamine play an important role in the pathophysiology of the disease. RLS is a complex genetic disorder, although no disease-causing gene has yet been identified. Dopaminergic therapy is currently the most effective treatment for this disease.

Key words:
restless legs syndrome – periodic limb movements during sleeping – dopaminergic therapy


1. Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005; 165(11): 1286–1292.

2. Hening W. The clinical neurophysiology of the restless legs syndrome and periodic limb movements. Part I. diagnosis, assessment, and characterization. Clin Neurophysiol 2004; 115(9): 1965–1974.

3. Coleman R. Periodic movements in sleep (nocturnal myoclonus) and restless legs syndrome. In: Guilleminault C et al (eds). Sleeping and waking disorders: indications and techniques. Menlo Park, CA: Addison-Wesley 1982: 265–295.

4. Iber C, Ancoli-Israel S, Chesson AL, Quan SF. The AASM Manual for the Scoring of Sleep and and Associated Events – Rules, Terminology and Technical Specifications. 1st ed. Westchester, IL: American Academy of Sleep Medicine 2007.

5. Harsh J, Peszka J, Hartwig G, Mitler M. Night-time sleep and daytime sleepiness in narcolepsy. J Sleep Res 2000; 9(3): 309–316.

6. Schenck CH, Mahowald MW. REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP Sleep 2002; 25(2): 120–138.

7. Warnes H, Dinner DS, Kotagal P, Burgess RC. Perio­dic limb movements and sleep apnoea. J Sleep Res 1993; 2(1): 38–44.

8. 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(6): 496–500.

9. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless Legs Syndrome Dia­gnosis and Epidemiology workshop at the Natio­nal Institutes of Health; International Restless Legs Syndrome Study Group, 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(2): 101–119.

10. Berger K, Luedemann J, Trenkwalder C, John U., Kessler C. Sex and the risk of restless legs syndrome in the general population. Arch Intern Med 2004; 164(2):196–202.

11. Valkovič P, Juračičová M, Ramos Rivera GA, Martinková J, Benetin J. Vyhľadávanie pacientov so syndrómom nepokojných nôh v čakárni klinickej ambulancie pomocou dotazníkovej metódy. Cesk Slov Neurol N 2009; 72/105(3): 250–254.

12. 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(5): 639–645.

13. Barrière G, Cazalets JR, Bioulac B, Tison F, Ghorayeb I. The restless legs syndrome. Progress Neurobiol 2005; 77(3): 139–165.

14. Šonka K. Syndrom neklidných nohou. Praha: Max­dorf 2008.

15. Scales, WE, Vander, AJ, Brown, MB, Kluger, MJ. Human circadian rhythms in temperature, trace metals, and blood variables. J Appl Physiol 1988; 65(4): 1840–1846.

16. Earley CJ, Connor JR, Beard JL. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 2000; 54(8): 1698–1700.

17. Schmidauer C, Sojer M, Seppi K, Stockner H, Hogl B, Biedermann B et al. Transcranial ultrasound shows nigral hypoechogenicity in restless legs syndrome. Ann Neurol 2005; 58(4): 630–634.

18. Connor JR, Wang XS, Patton SM, Menzies SL, Troncoso JC, Earley CJ et al. Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome. Neurology 2004; 62(9): 1563–1567.

19. Eisenstein RS. Iron regulatory proteins and the molecular control of mammalian iron metabolism. Annu Rev Nutr 2000; 20: 627–662.

20. Allen RP, Connor JR, Hyland K, Earley CJ. Abnormally increased CSF 3-Ortho-methyldopa (3-OMD) in untreated restless legs syndrome (RLS) patients indicates more severe disease and possibly abnormally increased dopamine synthesis. Sleep Med 2009; 10(1): 123–128.

21. Wang X, Wiesinger J, Beard J, Felt B, Menzies S, Earley C et al. Thy1 expression in the brain is affected by iron and is decreased in Restless Legs Syndrome. J Neurol Sci 2004; 220(1–2): 59–66.

22. Earley CJ, Heckler D, Allen RP. The treatment of restless legs syndrome with intravenous iron dextran. Sleep Med 2004; 5(3): 231–235.

23. Ondo WG, Vuong KD, Wang Q. Restless legs syndrome in monozygotic twins: Clinical correlates. Neurology 2000; 55(9): 1404–1407.

24. Winkelmann J, Polo O, Provini F, Nevsimalova S, Kemlink D, Sonka K et al. Genetics of restless legs syndrome (RLS): State-of-the-art and future directions. Mov Disord 2007; 22 (Suppl 18): S449–S458.

25. Kemlink D, Plazzi G, Vetrugno R, Provini F, Polo O, Stiasny-Kolster K et al. Suggestive evidence for linkage for Restless Legs Syndrome on Chromosome 19p13, Neurogenetics 2008; 9(2): 75–82.

26. Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 2007; 39(8): 1000–1006.

27. Stefansson H, Rye DB, Hicks A, Petursson H, Ingason A, Thorgeirsson TE et al. A genetic risk factor for periodic limb movements in sleep. N Engl J Med 2007; 357(7): 639–647.

28. Schormair B, Kemlink D, Roeske D, Eckstein G, Xiong L, Lichtner P et al. PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome. Nat Genet 2008; 40(8): 946–948.

29. Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 2003; 4(2) :121–132.

30. Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep 1996; 19(3): 205–213.

31. Šonka K, Nevšímalová S. Abnormální pohyby související se spánkem. In: Nevšímalová Š, Šonka K (eds). Poruchy spánku a bdění. Praha: Galén 2007: 243–265.

32. Kemlink D, Pretl M, Sonka K, Nevsimalova S. A comparison of polysomnographic and actigraphic evaluation of periodic limb movements in sleep. Neurol Res 2008; 30(3): 234–238.

33. Kemlink D. Periodické pohyby končetinami ve spánku. Neurol pro praxi 2008; 9(5): 290–293.

34. Benz RL, Pressman MR, Hovick ET, Peterson DD. A preliminary study of the effects of correction of anemia with recombinant human erythropoietin therapy on sleep, sleep disorders, and daytime sleepiness in hemodialysis patients (The SLEEPO study). Am J Kidney Dis 1999; 34(6): 1089–1095.

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

36. Kotagal S, Silber MH. Childhood-onset restless legs syndrome. Ann Neurol 2004; 56(6): 803–807.

37. Manconi M, Govoni V, De Vito A, Economou NT, Cesnik E, Casetta I et al. Restless legs syndrome and pregnancy. Neurology 2004; 63(6): 1065–1069.

38. Manconi M, Ferini-Strambi L, Filippi M, Bonanni E, Iudice A, Murri L et al. Multicenter case-control study on restless legs syndrome in multiple sclerosis: the REMS study. Sleep 2008; 31(7): 944–952.

39. Winkelmann J, Schadrack J, Wetter TC, Zieglgansberger W, Trenkwalder C. Opioid and dopamine antagonist drug challenges in untreated restless legs syndrome patients. Sleep Med 2001; 2(1): 57–61.

40. Rottach KG, Schaner BM, Kirch MH, Zivotofsky AZ, Teufel LM, Gallwitz T et al. Restless legs syndrome as side effect of second generation antidepressants. J Psychiatr Res 2008; 43(1): 70–75.

41. Brown LK, Dedrick DL, Doggett JW, Guido PS. Antidepressant medication use and restless legs syndrome in patients presenting with insomnia. Sleep Med 2005; 6(5): 443–450.

42. Earley CJ, Silber MH. Restless legs syndrome: understanding its consequences and the need for better treatment. Sleep Med 2010; 11(9): 807–815.

43. Allen R, Chen C, Soaita A, Wohlberg C, Knapp L, Peterson BT et al. A randomized, double-blind, 6-week, dose-ranging study of pregabalin in patients with restless legs syndrome. Sleep Med 2010; 11(6): 512–519.

Dětská neurologie Neurochirurgie Neurologie

Článek vyšel v časopise

Česká a slovenská neurologie a neurochirurgie

Číslo 2

2011 Číslo 2

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…

Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se