Journal of Neurology

, 253:vii33 | Cite as

Restless Legs Syndrome and Parkinson’s Disease: Is there an etiologic link?

Article

Abstract

The etiologic link between restless legs syndrome (RLS) and Parkinson’s disease (PD) has been debated. Since dopaminergic dysfunction and response to dopaminergic agents are consistent features in RLS and PD, some authors have suggested that these two diseases may share common pathophysiology. However, presently there is not enough evidence to suggest that the actual pathophysiologic mechanism in both diseases is identical. The nigrostriatal dopaminergic system is primarily involved in PD and it is possible that the extrastriatal dopaminergic system may be variably involved in those PD patients with RLS symptoms.

Further clinical, imaging, pharmacologic, and genetic studies will be needed to address the many unanswered questions related to the link between RLS and PD.

Key words

Parkinson’s disease RLS 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Ekbom KA (1945) Restless legs. Acta Med Scand 158(Suppl):1–124Google Scholar
  2. 2.
    Rothdach AJ, Trenkwalder C, Haberstock J, Keil U, Berger K (2000) Prevalence and risk factors of RLS in an elderly population: the MEMO Memory and Morbidity in Augsburg Elderly. Neurology 54:1064–1068PubMedGoogle Scholar
  3. 3.
    Tan EK, Seah A, See SJ, Lim E, Wong MC, Koh KK (2001) Restless Legs Syndrome in an Asian population: a study in Singapore. Mov Disord 16(3):577–579PubMedCrossRefGoogle Scholar
  4. 4.
    Wetter TC, Pollmacher T (1997) Restless legs and periodic leg movements in sleep syndromes. J Neurol 244 (Suppl):S37–S45PubMedCrossRefGoogle Scholar
  5. 5.
    Walters AS and The International Restless Legs Syndrome Study Group (1995) Mov Disord 10:634–642PubMedCrossRefGoogle Scholar
  6. 6.
    Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J (2003) 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 4(2):101–119PubMedCrossRefGoogle Scholar
  7. 7.
    Ondo WG, Jankovic J (1996) Restless Legs Syndrome: clinico-radiologic correlates. Neurology 47:1435–1441PubMedGoogle Scholar
  8. 8.
    Tan EK, Ondo W (2000) Restless legs syndrome: clinical features and treatment. Am J Med Sci 319(6):397–403PubMedCrossRefGoogle Scholar
  9. 9.
    Tan EK, Ondo WG (2001) Motor restlessness. Int J Clin Pract 55(5):320–322PubMedGoogle Scholar
  10. 10.
    O’Keeffe ST, Noel J, Lavan JN (1993) Restless legs syndrome in the elderly. Postgrad Med J 69:701–703PubMedGoogle Scholar
  11. 11.
    Chokroverty S, Jankovic J (1999) Restless legs syndrome: a disease in search of an identity. Neurology 52:907–910PubMedGoogle Scholar
  12. 12.
    Coleman RM, Pollak CP, Weitzman ED (1980) Periodic movements in sleep (nocturnal myoclonus): relation to sleep disorders. Ann Neurol 8:416–421PubMedCrossRefGoogle Scholar
  13. 13.
    Ehrenberg BL (1992) Sleep pathologies associated with nocturnal movements. In: Joseph AB, Young RR (eds) Movement Disorders in Neurology and Psychiatry. Boston, Blackwell scientific, pp 634–648Google Scholar
  14. 14.
    Montplaisir J, Boucher S, Poirier G et al. (1997) Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: A study of 133 patients diagnosed with new standard of criteria. Mov Disord 1:61–65CrossRefGoogle Scholar
  15. 15.
    Jankovic J (2001) Parkinson’s disease. A half century of progress. Neurology 57(10 Suppl 3):S1–S3PubMedCrossRefGoogle Scholar
  16. 16.
    Tan EK, Khajavi M, Thornby JI, Nagamitsu S, Jankovic J, Ashizawa T (2000) Variability and validity of polymorphism association studies in Parkinson’s disease. Neurology 55:533–538PubMedGoogle Scholar
  17. 17.
    Tan EK, Jankovic J (2006) Genetic testing in Parkinson’s disease: promises and pitfalls. Arch Neurol 63:1232–1237PubMedCrossRefGoogle Scholar
  18. 18.
    Nomura T, Inoue Y, Miyake M, Yasui K, Nakashima K (2006) Prevalence and clinical characteristics of restless legs syndrome in Japanese. patients with Parkinson’s disease. Mov Disord 21(3):380–384PubMedCrossRefGoogle Scholar
  19. 19.
    Krishnan PR, Bhatia M, Behari M (2002) Restless legs syndrome in Parkinson’s disease: a case controlled study. Mov Disord 18:181–185CrossRefGoogle Scholar
  20. 20.
    Tan EK, Lum SY, Wong MC (2002) Restless legs syndrome in Parkinson’s disease. J Neurol Sci 196(1–2):33–36PubMedCrossRefGoogle Scholar
  21. 21.
    Ondo WG, Vuong KD, Jankovic J (2002) Exploring the relationship between Parkinson disease and restless legs syndrome. Arch Neurol 59:421–424 PubMedCrossRefGoogle Scholar
  22. 22.
    Kedia S, Moro E, Tagliati M, Lang AE, Kumar R (2004) Emergence of restless legs syndrome during subthalamic stimulation for Parkinson disease. Neurology 63(12):2410–2412PubMedGoogle Scholar
  23. 23.
    Tan EK, Yew K, Chua E et al. (2006) PINK1 mutations in sporadic early-onset Parkinson’s disease. Mov Disord 21(6):789–793PubMedCrossRefGoogle Scholar
  24. 24.
    Adel S, Djarmati A, Kabakci K et al. (2006) Co-occurrence of restless legs syndrome and Parkin mutations in two families. Mov Disord 21(2):258–263PubMedCrossRefGoogle Scholar
  25. 25.
    Lesperance P, Djerroud N, Diaz Anzaldua A, Rouleau GA, Chouinard S, Richer F; Montreal Tourette Study Group (2004) Restless legs in Tourette syndrome. Mov Disord 19(9):1084–1087PubMedCrossRefGoogle Scholar
  26. 26.
    Evers S, Stogbauer F (2003) Genetic association of Huntington’s disease and restless legs syndrome? A family report. Mov Disord 18(2):225–227PubMedCrossRefGoogle Scholar
  27. 27.
    Tan EK, Ho SC, Eng P, Loh LM, Koh L, Lum SY, Teoh ML, Yih Y, Khoo D (2004) Restless legs symptoms in thyroid disorders. Parkinsonism Relat Disord 10(3):149–151PubMedCrossRefGoogle Scholar
  28. 28.
    Tan EK, Ho SC, Koh L, Pavanni R (2004) An urge to move with L-thyroxine: clinical, biochemical, and polysomnographic correlation. Mov Disord 19(11):1365–1367PubMedCrossRefGoogle Scholar
  29. 29.
    Ondo WG, Lai D (2006) Association between restless legs syndrome and essential tremor. Mov Disord 21(4):515–518PubMedCrossRefGoogle Scholar
  30. 30.
    Aldrich MS (2000) Parkinsonism. In: Kryger M, Roth T, Dement W (eds) Principles and practice of sleep medicine. 3rd ed. Philadelphia: WB Saunders, pp 1051–1057Google Scholar
  31. 31.
    Pollmacher T, Schulz H (1993) Periodic leg movements (PLM): their relationship to sleep stages. Sleep 16:572–577PubMedGoogle Scholar
  32. 32.
    Wetter TH, Collado-Seidel V, Pollmächer T, Yassouridis A, Trenkwalder C (2000) Sleep and periodic leg movement patterns in drug-free patients with Parkinson’s disease and multiple system atrophy. Sleep 23:361–367PubMedGoogle Scholar
  33. 33.
    Michaud M, Soucy JP, Chabli A, Lavigne G, Montplaisir J (2002) SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep. J Neurol 249:164–170PubMedCrossRefGoogle Scholar
  34. 34.
    Turjanski N, Lees AJ, Brooks DJ (1999) Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11Craclopride PET studies. Neurology 52:932–937PubMedGoogle Scholar
  35. 35.
    Eisensehr I, Wetter TC, Linke R et al. (2001) Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome. Neurology 57:1307–1309PubMedGoogle Scholar
  36. 36.
    Ruottinen HM, Partinen M, Hublin C et al. (2000) An FDOPA PET study in patients with periodic limb movement disorder and restless legs syndrome. Neurology 54:502–504Google Scholar
  37. 37.
    Trenkwalder C, Walters AS, Hening WA et al. (1999) Positron emission tomographic studies in restless legs syndrome. Mov Disord 14:141–145PubMedCrossRefGoogle Scholar
  38. 38.
    Boyer P, Ondo W, Allen R (2000) Neuropathologic evaluation of the central nervous system in restless legs syndrome: case report and review of the literature. Soc Neurosci 2:2060. AbstractGoogle Scholar
  39. 39.
    Pittock SJ, Parrett T,Adler CH, Parisi JE, Dickson DW, Ahlskog JE (2004) Neuropathology of primary restless leg syndrome: absence of specific tau- and alpha-synuclein pathology. Mov Disord 19(6):695–699PubMedCrossRefGoogle Scholar
  40. 40.
    Ondo WG, He Y, Rajasekaran S, Le WD (2000) Clinical correlates of 6-hydroxydopamine injections into A11 dopaminergic neurons in rats: a possible model for restless legs syndrome. Mov Disord 15(1):154–158PubMedCrossRefGoogle Scholar
  41. 41.
    Walters AS, Hening W, Rubinstein M, Chokroverty S (1991) A clinical and polysomnographic comparison of neuroleptic induced akathisia and the idiopathic restless legs syndrome. Sleep 14:339–345PubMedGoogle Scholar
  42. 42.
    Comella CL, Goetz CG (2003) Akathisia in Parkinson’s disease. Mov Disord 9:545–549CrossRefGoogle Scholar
  43. 43.
    Riley DE, Lang AE (1993) The spectrum of levodopa-related fluctuations in Parkinson’s disease. Neurology 43:1459–1464PubMedGoogle Scholar
  44. 44.
    Earley CJ, Connor JR, Beard JL, Malecki EA, Epstein DK, Allen RP (2000) Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology 54:1698–1700PubMedGoogle Scholar
  45. 45.
    O’Keeffe ST, Galvin K, Lavan JN (1994) Iron status and restless legs syndrome in the elderly. Age Ageing 23:200–203PubMedGoogle Scholar
  46. 46.
    Krieger J, Schroeder C (2001) Iron, brain and restless legs syndrome. Sleep Med Rev 5:277–286PubMedCrossRefGoogle Scholar
  47. 47.
    Sun ER, Chen CA, Ho G, Earley CJ, Allen RP (1998) Iron and the restless legs syndrome. Sleep 21:371–377PubMedGoogle Scholar
  48. 48.
    O’Keeffe ST, Noel J, Lavan JN (1993) Restless legs syndrome in the elderly. Postgrad Med J 69:701–703PubMedCrossRefGoogle Scholar
  49. 49.
    Earley CJ, Allen RP, Beard JL, Connor JR (2000) Insight into the pathophysiology of restless legs syndrome. J Neurosci Res 62:623–628PubMedCrossRefGoogle Scholar
  50. 50.
    Allen RP, Barker PB, Wehrl F, Song HK, Earley CJ (2001) MRI measurement of brain iron in patients with restless legs syndrome. Neurology 56(2):263–265PubMedGoogle Scholar
  51. 51.
    Schmidauer C, Sojer M, Seppi K et al. (2005) Transcranial ultrasound shows nigral hypoechogenicity in restless legs syndrome. Ann Neurol 58(4):630–634PubMedCrossRefGoogle Scholar
  52. 52.
    Connor JR, Wang XS, Patton SM, Menzies SL, Troncoso JC, Earley CJ, Allen RP (2004) Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome. Neurology 62(9):1563–1567PubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  1. 1.Parkinson’s Disease and Movement Disorder Program, Department of NeurologySingapore General HospitalSingapore 169608Republic of Singapore

Personalised recommendations