Advertisement

Restless Legs Syndrome and Periodic Limb Movements in Parkinson’s Disease

  • William G. OndoEmail author
Chapter

Abstract

The symptoms of Parkinson’s disease (PD) commonly include a number of sleep disorders, including restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS). RLS occurs in about 20 % of PD patients in most studies, but idiopathic RLS does not seem to precede the development of PD. In fact there is some evidence that idiopathic RLS may prevent the subsequent development of PD. In cases of PD/RLS the PD usually presents first, and RLS may represent one of many non-motor features associated with PD. Although common, RLS is usually not a major contributor to sleep deprivation or functional impairment in the PD population. PLMS are seen in many neurodegenerative disorders, as well as idiopathic RLS. Most studies report higher rates of PLMS in PD, but polysomnography studies suggest relatively little impact of PLMS on other sleep measures. The response of both PD and RLS to dopaminergics is of great interest, especially given the lack of overt dopamine pathology in RLS.

Keywords

Deep Brain Stimulation Periodic Limb Movement Periodic Limb Movement Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Wetter TC, et al. Sleep and periodic leg movement patterns in drug-free patients with Parkinson’s disease and multiple system atrophy. Sleep. 2000;23(3):361–7.PubMedGoogle Scholar
  2. 2.
    Horiguchi J, et al. [Sleep-wake complaints in Parkinson’s disease]. Rinsho Shinkeigaku Clin Neurol. 1990;30(2):214–6.Google Scholar
  3. 3.
    Banno K, et al. Restless legs syndrome in 218 patients: associated disorders. Sleep Med. 2000;1(3):221–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Lang AE. Restless legs syndrome and Parkinson’s disease: insights into pathophysiology. Clin Neuropharmacol. 1987;10(5):476–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Paulson G. Is restless legs a prodrome to Parkinson’s disease. Mov Disord. 1997;12 Suppl 1:68.Google Scholar
  6. 6.
    Allen RP, 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(2):101–19.CrossRefPubMedGoogle Scholar
  7. 7.
    Ondo W, Jankovic J. Restless legs syndrome: clinicoetiologic correlates. Neurology. 1996;47(6):1435–41.CrossRefPubMedGoogle Scholar
  8. 8.
    Hening W, et al. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med. 2004;5(3):237–46.CrossRefPubMedGoogle Scholar
  9. 9.
    Tan EK, et al. Restless legs syndrome in an Asian population: a study in Singapore. Mov Disord. 2001;16(3):577–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Winkelmann J, et al. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet. 2007;39(8):1000–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Stefansson H, et al. A genetic risk factor for periodic limb movements in sleep. N Engl J Med. 2007;357(7):639–47.CrossRefPubMedGoogle Scholar
  12. 12.
    Chen S, et al. Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p. Am J Hum Genet. 2004;74(5):876–85.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Desautels A, et al. Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q. [see comment]. Am J Hum Genet. 2001;69(6):1266–70.CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Bonati MT, et al. Autosomal dominant restless legs syndrome maps on chromosome 14q. Brain. 2003;126(Pt 6):1485–92.CrossRefPubMedGoogle Scholar
  15. 15.
    Earley CJ, et al. Abnormalities in CSF concentrations of ferritin and transferrin in restless legs syndrome. Neurology. 2000;54(8):1698–700.CrossRefPubMedGoogle Scholar
  16. 16.
    Schmidauer C, et al. Brain parenchyma sonography differentiates RLS patients from normal controls and patients with Parkinson’s disease. Mov Disord. 2005;20 Suppl 10:S43.Google Scholar
  17. 17.
    Allen RP, et al. MRI measurement of brain iron in patients with restless legs syndrome. Neurology. 2001;56(2):263–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Connor JR, et al. Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome. Neurology. 2004;62(9):1563–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Connor JR, et al. Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology. 2003;61(3):304–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Ryu JH, Lee MS, Baik JS. Sonographic abnormalities in idiopathic restless legs syndrome (RLS) and RLS in Parkinson’s disease. Parkinsonism Relat Disord. 2010;17(3):201–3.CrossRefPubMedGoogle Scholar
  21. 21.
    Kwon DY, et al. Transcranial brain sonography in Parkinson’s disease with restless legs syndrome. Mov Disord. 2010;25(10):1373–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Garcia-Borreguero D, et al. Circadian variation in neuroendocrine response to L-dopa in patients with restless legs syndrome. Sleep. 2004;27(4):669–73.PubMedGoogle Scholar
  23. 23.
    Trenkwalder C, et al. Positron emission tomographic studies in restless legs syndrome. Mov Disord. 1999;14(1):141–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Ruottinen HM, et al. An FDOPA PET study in patients with periodic limb movement disorder and restless legs syndrome. Neurology. 2000;54(2):502–4.CrossRefPubMedGoogle Scholar
  25. 25.
    Turjanski N, Lees AJ, Brooks DJ. Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies. Neurology. 1999;52(5):932–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Michaud M, et al. SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep. J Neurol. 2002;249(2):164–70.CrossRefPubMedGoogle Scholar
  27. 27.
    Linke R, et al. Presynaptic dopaminergic function in patients with restless legs syndrome: are there common features with early Parkinson’s disease? Mov Disord. 2004;19(10):1158–62.CrossRefPubMedGoogle Scholar
  28. 28.
    Eisensehr I, et al. Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome. Neurology. 2001;57(7):1307–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Earley CJ, et al. The dopamine transporter is decreased in the striatum of subjects with restless legs syndrome. Sleep. 2011;34(3):341–7.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Qu S, et al. Locomotion is increased in a11-lesioned mice with iron deprivation: a possible animal model for restless legs syndrome. J Neuropathol Exp Neurol. 2007;66(5):383–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Stiasny-Kolster K, et al. Normal dopaminergic and serotonergic metabolites in cerebrospinal fluid and blood of restless legs syndrome patients. Mov Disord. 2004;19(2):192–6.CrossRefPubMedGoogle Scholar
  32. 32.
    Earley CJ, Hyland K, Allen RP. CSF dopamine, serotonin, and biopterin metabolites in patients with restless legs syndrome. Mov Disord. 2001;16(1):144–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Earley CJ, Hyland K, Allen RP. Circadian changes in CSF dopaminergic measures in restless legs syndrome. Sleep Med. 2006;7(3):263–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Pittock SJ, et al. Neuropathology of primary restless leg syndrome: absence of specific tau- and alpha-synuclein pathology. Mov Disord. 2004;19(6):695–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Ye Z, Connor JR. Identification of iron responsive genes by screening cDNA libraries from suppression subtractive hybridization with antisense probes from three iron conditions. Nucleic Acids Res. 2000;28(8):1802–7.CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Wang X, 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.CrossRefPubMedGoogle Scholar
  37. 37.
    Jeng CJ, et al. Thy-1 is a component common to multiple populations of synaptic vesicles. J Cell Biol. 1998;140(3):685–98.CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Vilarino-Guell C, et al. Susceptibility genes for restless legs syndrome are not associated with Parkinson disease. Neurology. 2008;71(3):222–3.CrossRefPubMedGoogle Scholar
  39. 39.
    Adel S, et al. Co-occurrence of restless legs syndrome and Parkin mutations in two families. Mov Disord. 2006;21(2):258–63.CrossRefPubMedGoogle Scholar
  40. 40.
    Pichler I, et al. Parkin gene modifies the effect of RLS4 on the age at onset of restless legs syndrome (RLS). Am J Med Genet B Neuropsychiatr Genet. 2010;153B(1):350–5.PubMedGoogle Scholar
  41. 41.
    Ondo WG, Vuong KD, Jankovic J. Exploring the relationship between Parkinson disease and restless legs syndrome. Arch Neurol. 2002;59(3):421–4.CrossRefPubMedGoogle Scholar
  42. 42.
    Driver-Dunckley E, et al. Restless legs syndrome in Parkinson’s disease patients may improve with subthalamic stimulation. Mov Disord. 2006;21(8):1287–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Peralta CM, et al. Restless legs syndrome in Parkinson’s disease. Mov Disord. 2009;24:2076–80.CrossRefPubMedGoogle Scholar
  44. 44.
    Simuni T, Wilson R, Stern MB. Prevalence of restless legs syndrome in Parkinson’s disease. Mov Disord. 2000;15(Supple 5):1043.Google Scholar
  45. 45.
    Braga-Neto P, et al. Snoring and excessive daytime sleepiness in Parkinson’s disease [erratum appears in J Neurol Sci. 2004;219(1–2):171]. J Neurol Sci. 2004;217(1):41–5.Google Scholar
  46. 46.
    Chaudhuri KR, et al. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord. 2006;21(7):916–23.CrossRefPubMedGoogle Scholar
  47. 47.
    Verbaan D, et al. Prevalence and clinical profile of restless legs syndrome in Parkinson’s disease. Mov Disord. 2010;25(13):2142–7.CrossRefPubMedGoogle Scholar
  48. 48.
    Loo HV, Tan EK. Case-control study of restless legs syndrome and quality of sleep in Parkinson’s disease. J Neurol Sci. 2008;266(1–2):145–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Kumar S, Bhatia M, Behari M. Sleep disorders in Parkinson’s disease. Mov Disord. 2002;17(4):775–81.CrossRefPubMedGoogle Scholar
  50. 50.
    Krishnan PR, Bhatia M, Behari M. Restless legs syndrome in Parkinson’s disease: a case-controlled study. Mov Disord. 2003;18(2):181–5.CrossRefPubMedGoogle Scholar
  51. 51.
    Nomura T, et al. Prevalence and clinical characteristics of restless legs syndrome in Japanese patients with Parkinson’s disease. Mov Disord. 2006;21(3):380–4.CrossRefPubMedGoogle Scholar
  52. 52.
    Tan EK, Lum SY, Wong MC. Restless legs syndrome in Parkinson’s disease. J Neurol Sci. 2002;196(1–2):33–6.CrossRefPubMedGoogle Scholar
  53. 53.
    Rijsman RM, et al. Restless legs syndrome in Parkinson’s disease. Parkinsonism Relat Disord. 2014;20 Suppl 1:S5–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Gjerstad MD, Tysnes OB, Larsen JP. Increased risk of leg motor restlessness but not RLS in early Parkinson disease. Neurology. 2011;77(22):1941–6.CrossRefPubMedGoogle Scholar
  55. 55.
    Fazzini E, Diaz R, Fahn S. Restless legs in Parkinson’s disease-clinical evidence for underactivity of catecholamine neurotransmission. [abstract]. Ann Neurol. 1989;26:142.Google Scholar
  56. 56.
    Walters AS, et al. A preliminary look at the percentage of patients with Restless Legs Syndrome who also have Parkinson Disease, Essential Tremor or Tourette Syndrome in a single practice. J Sleep Res. 2003;12(4):343–5.CrossRefPubMedGoogle Scholar
  57. 57.
    Gao X, et al. Restless legs syndrome and Parkinson’s disease in men. Mov Disord. 2010;25(15):2654–7.CrossRefPubMedCentralPubMedGoogle Scholar
  58. 58.
    Wong JC, et al. Restless legs syndrome: an early clinical feature of Parkinson disease in men. Sleep. 2014;37(2):369–72.PubMedCentralPubMedGoogle Scholar
  59. 59.
    Ancoli-Israel S, et al. Periodic limb movements in sleep in community-dwelling elderly. Sleep. 1991;14(6):496–500.PubMedGoogle Scholar
  60. 60.
    Mosko SS, et al. Sleep apnea and sleep-related periodic leg movements in community resident seniors. J Am Geriatr Soc. 1988;36(6):502–8.PubMedGoogle Scholar
  61. 61.
    Bara-Jimenez W, et al. Periodic limb movements in sleep: state-dependent excitability of the spinal flexor reflex. [comment]. Neurology. 2000;54(8):1609–16.CrossRefPubMedGoogle Scholar
  62. 62.
    Pennestri MH, et al. Nocturnal blood pressure changes in patients with restless legs syndrome. Neurology. 2007;68(15):1213–8.CrossRefPubMedGoogle Scholar
  63. 63.
    Walters AS, Rye DB. Evidence continues to mount on the relationship of restless legs syndrome/periodic limb movements in sleep to hypertension, cardiovascular disease, and stroke. Sleep. 2010;33(3):287.PubMedCentralPubMedGoogle Scholar
  64. 64.
    Winkelman JW, et al. Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study. Neurology. 2008;70(1):35–42.CrossRefPubMedGoogle Scholar
  65. 65.
    Montplaisir J, 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(1):61–5.CrossRefPubMedGoogle Scholar
  66. 66.
    Coleman RM, et al. Sleep-wake disorders in the elderly: polysomnographic analysis. J Am Geriatr Soc. 1981;29(7):289–96.PubMedGoogle Scholar
  67. 67.
    Trenkwalder C. Sleep dysfunction in Parkinson’s disease. Clin Neurosci. 1998;5(2):107–14.PubMedGoogle Scholar
  68. 68.
    Covassin N, et al. Clinical correlates of periodic limb movements in sleep in Parkinson’s disease. J Neurol Sci. 2012;316(1–2):131–6.CrossRefPubMedCentralPubMedGoogle Scholar
  69. 69.
    Wetter TC, et al. Polysomnographic measures in Parkinson’s disease: a comparison between patients with and without REM sleep disturbances. Wien Klin Wochenschr. 2001;113(7–8):249–53.PubMedGoogle Scholar
  70. 70.
    Ma JF, et al. Efficacy and safety of pramipexole in chinese patients with restless legs syndrome: results from a multi-center, randomized, double-blind, placebo-controlled trial. Sleep Med. 2012;13(1):58–63.CrossRefPubMedGoogle Scholar
  71. 71.
    Happe S, et al. Periodic leg movements in patients with Parkinson’s disease are associated with reduced striatal dopamine transporter binding. J Neurol. 2003;250(1):83–6.CrossRefPubMedGoogle Scholar
  72. 72.
    Hogl B, et al. The effect of cabergoline on sleep, periodic leg movements in sleep, and early morning motor function in patients with Parkinson’s disease. Neuropsychopharmacology. 2003;28(10):1866–70.CrossRefPubMedGoogle Scholar
  73. 73.
    Shpirer I, et al. Excessive daytime sleepiness in patients with Parkinson’s disease: a polysomnography study. Mov Disord. 2006;21(9):1432–8.CrossRefPubMedGoogle Scholar
  74. 74.
    Rye DB, DeLong MR. Amelioration of sensory limb discomfort of restless legs syndrome by pallidotomy. Ann Neurol. 1999;46(5):800–1.CrossRefPubMedGoogle Scholar
  75. 75.
    Chahine LM, Ahmed A, Sun Z. Effects of STN DBS for Parkinson’s disease on restless legs syndrome and other sleep-related measures. Parkinsonism Relat Disord. 2011;17(3):208–11.CrossRefPubMedGoogle Scholar
  76. 76.
    Kedia S, et al. Emergence of restless legs syndrome during subthalamic stimulation for Parkinson disease. Neurology. 2004;63(12):2410–2.CrossRefPubMedGoogle Scholar
  77. 77.
    Parra J, et al. [Severe restless legs syndrome following bilateral subthalamic stimulation to treat a patient with Parkinson’s disease]. Rev Neurol. 2006;42(12):766–7.PubMedGoogle Scholar
  78. 78.
    Ondo WG, et al. Globus pallidus deep brain stimulation for refractory idiopathic restless legs syndrome. Sleep Med. 2012;13(9):1202–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Texas Health Science Center-HoustonHoustonUSA

Personalised recommendations