Current Treatment Options in Neurology

, Volume 14, Issue 5, pp 464–473 | Cite as

Sleep Dysfunction in Multiple System Atrophy

SLEEP DISORDERS (S CHOKROVERTY, SECTION EDITOR)
First Online:

Opinion statement

Sleep disorders in multiple system atrophy (MSA) are common manifestation and include reduced and fragmented sleep, excessive daytime sleepiness, REM sleep behaviour disorder (RBD), and sleep-disordered breathing. Of these, RBD is the most common (affecting 90 %–100 % of patients with MSA) and is regarded as a red flag for MSA. RBD, as well as stridor during sleep, may be the initial manifestation of the disease, occurring several years before the waking motor and dysautonomic onset. Sleep disorders occur in both MSA with predominant parkinsonism (MSA-P) and MSA with predominant cerebellar ataxia (MSA-C). Treatment strategies in patients with MSA presenting difficulties in initiating and maintaining sleep need to be highly individualized. Clonazepam has been found to be successful in treating RBD symptoms at the dose of 0.25 to 2.0 mg given approximately 30 min before bedtime. In case of comorbid obstructive sleep apnea, zopiclone (at the dose from 3.75 to 7.5 mg each night) or melatonin (with a recommended dose of 3 to 12 mg at bedtime) may be alternative treatments. An increased survival in MSA patients with stridor may be obtained both with continuous positive airway pressure (CPAP) and tracheostomy. Since tracheostomy is an invasive surgical procedure, not easily accepted by the patient, CPAP therapy should be considered first. However, tracheostomy is first indicated when stridor is present during wakefulness because of the high risk of respiratory failure and death. In MSA, obstructive sleep apnea (OSA) occurs more frequently than central sleep apnea, ranging from 15 % to 37 % of the cases. CPAP is an effective treatment for eliminating obstructive sleep apnea in MSA patients, even if the adaptation to the device may be difficult in advanced cases.

Keywords

Multiple system atrophy Sleep Excessive daytime sleepiness REM sleep Behavior disorders Stridor Central apnea Obstructive sleep apnea Sleep dysfunction Treatment 
This is a preview of subscription content, log in to check access.

Notes

Disclosure

Dr. Ferini-Strambi has served on boards for UCB Pharma, Boehringer-Ingelheim, and Angelini.

Dr. Marelli reported no potential conflicts of interest relevant to this article.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.••
    Ubhi K, Low P, Masliah E. Multiple system atrophy: a clinical and neuropathological perspective. Trends Neurosci. 2011;34(11):581–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Colosimo C. Nonmotor presentations of multiple system atrophy. Nat Rev Neurol. 2011;7(5):295–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Fellner L, Jellinger KA, Wenning GK, et al. Glial dysfunction in the pathogenesis of α-synucleinopathies: emerging concepts. Acta Neuropathol. 2011;121(6):675–93.PubMedCrossRefGoogle Scholar
  4. 4.
    Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci. 1999;163:94–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71:670–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Wenning GK, Colosimo C, Geser F, et al. Multiple system atrophy. Lancet Neurol. 2004;3:93–103.PubMedCrossRefGoogle Scholar
  7. 7.
    Watanabe H, Saito Y, Terao S, et al. Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. Brain. 2002;125:1070–83.PubMedCrossRefGoogle Scholar
  8. 8.
    Plazzi G, Corsini R, Provini F, et al. REM sleep behavior disorders in multiple system atrophy. Neurology. 1997;48:1094–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Tachibana N, Kimura K, Kitajima K, et al. REM sleep motor dysfunction in multiple system atrophy: With special emphasis on sleep talk as its early clinical manifestation. J Neurol Neurosurg Psychiatry. 1997;63:678–81.PubMedCrossRefGoogle Scholar
  10. 10.
    Iranzo A, Rye DB, Santamaria J, et al. Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD. Neurology. 2005;65:247–52.PubMedCrossRefGoogle Scholar
  11. 11.
    Köllensperger M, Geser F, Seppi K, et al. Red flags for multiple system atrophy. Mov Disord. 2008;23(8):1093–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Gama RL, Távora DG, Bonfim RC, et al. Sleep disturbances and brain MRI morphometry in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a comparative study. Parkinsonism Relat Disord. 2010;16(4):275–9.PubMedCrossRefGoogle Scholar
  13. 13.••
    Moreno-López C, Santamaría J, Salamero M, et al. Excessive daytime sleepiness in multiple system atrophy (SLEEMSA study). Arch Neurol. 2011;68:223–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Beck RO, Betts CD, Fowler CJ. Genitourinary dysfunction in multiple system atrophy: clinical features and treatment in 62 cases. J Urol. 1994;151:1336–41.PubMedGoogle Scholar
  15. 15.
    Ghorayeb I, Yekhlef F, Chrysostome V, et al. Sleep disorders and their determinants in multiple system atrophy. J Neurol Neurosurg Psychiatry. 2002;72(6):798–800.PubMedCrossRefGoogle Scholar
  16. 16.
    Högl B, Seppi K, Brandauer E, et al. Irresistible onset of sleep during acute levodopa challenge in a patient with multiple system atrophy (MSA): placebo-controlled, polysomnographic case report. Mov Disord. 2001;16(6):1177–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Seppi K, Högl B, Diem A, et al. Levodopa-induced sleepiness in the Parkinson variant of multiple system atrophy. Mov Disord. 2006;21(8):1281–3.PubMedCrossRefGoogle Scholar
  18. 18.
    Homann CN, Homann B, Ott E, et al. Sleep attacks may not be a side effect of dopaminergic medication. Mov Disord. 2003;18(12):1569–70.PubMedCrossRefGoogle Scholar
  19. 19.
    Martinez-Rodriguez JE, Seppi K, Cardozo A, et al. SINBAR (Sleep Innsbruck Barcelona) group. Cerebrospinal fluid hypocretin-1 levels in multiple system atrophy. Mov Disord. 2007;22(12):1822–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Arnulf I. Excessive daytime sleepiness in parkinsonism. Sleep Med Rev. 2005;9(3):185–200.PubMedCrossRefGoogle Scholar
  21. 21.
    Benarroch EE, Schmeichel AM, Sandroni P, et al. Involvement of hypocretin neurons in multiple system atrophy. Acta Neuropathol. 2007;113:75–80.PubMedCrossRefGoogle Scholar
  22. 22.
    Mignot E, Lammers GJ, Ripley B, et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol. 2002;59:1553–62.PubMedCrossRefGoogle Scholar
  23. 23.
    Drouot X, Moutereau S, Nguyen JP, et al. Low levels of ventricular CSF orexin/hypocretin in advanced PD. Neurology. 2003;61:540–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Abdo WF, Bloem BR, Kremer HP, et al. CSF hypocretin-1 levels are normal in multiple-system atrophy. Parkinsonism Relat Disord. 2008;14(4):342–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Schenck CH, Bundlie SR, Patterson AL, et al. Rapid eye movement sleep behavior disorder. A treatable parasomnia affecting older adults. JAMA. 1987;257:1786–9.PubMedCrossRefGoogle Scholar
  26. 26.••
    Boeve BF. REM sleep behavior disorder: updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions. Ann N Y Acad Sci. 2010;1184:15–54.PubMedCrossRefGoogle Scholar
  27. 27.
    American Academy of Sleep Medicine. REM sleep behavior disorder. In: International Classification of Sleep Disorders. In: Diagnostic and Coding Manual. 2nd ed. Westchester: American Academy of Sleep Medicine; 2005. p. 148–52.Google Scholar
  28. 28.
    Ferini-Strambi L. Does idiopathic REM sleep behavior disorder (iRBD) really exist? What are the potential markers of neurodegeneration in iRBD? Sleep Med. 2011;(Suppl 2):S43–49.Google Scholar
  29. 29.
    Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38 % of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology. 1996;46:388–93.PubMedCrossRefGoogle Scholar
  30. 30.
    Schenck C, Bundlie SR, Mahowald MW. REM behavior disorder (RBD): delayed emergence of parkinsonism and/or dementia in 65 % of older men initially diagnosed with idiopathic RBD, and an analysis of the minimum and maximum tonic and/or phasic electromyographic abnormalities found during REM sleep. Sleep. 2003;26:A316.Google Scholar
  31. 31.
    Iranzo A, Molinuevo JL, Santamaria J, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006;5:572–7.PubMedCrossRefGoogle Scholar
  32. 32.••
    Postuma RB, Gagnon JF, Vendette M, et al. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology. 2009;72:1296–300.PubMedGoogle Scholar
  33. 33.
    Vetrugno R, Provini F, Cortelli P, et al. Sleep disorders in multiple system atrophy: a correlative video-polysomnographic study. Sleep Med. 2004;5:21–30.PubMedCrossRefGoogle Scholar
  34. 34.
    Claassen DO, Josephs KA, Ahlskog JE, et al. REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010;75:494–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Nomura T, Inoue Y, Högl B, et al. Comparison of the clinical features of rapid eye movement sleep behavior disorder in patients with Parkinson's disease and multiple system atrophy. Psychiat Clin Neurosci. 2011;65:264–71.CrossRefGoogle Scholar
  36. 36.
    Iranzo A, Santamaria J, Tolosa E. The clinical and pathological relevance of REM sleep behavior disorder in neurodegenerative disease. Sleep Med Rev. 2009;13:385–401.PubMedCrossRefGoogle Scholar
  37. 37.
    McCarter SJ, St Louis EK, Boeve BF. REM sleep behavior disorder and REM sleep without atonia as an early manifestation of degenerative neurological disease. Curr Neurol Neurosci Rep. 2012;12(2):182–92.PubMedCrossRefGoogle Scholar
  38. 38.
    Howell MJ, Arneson PA, Schenck CH. A novel therapy for REM sleep behavior disorder (RBD). J Clin Sleep Med. 2011;7(6):639–44A.PubMedGoogle Scholar
  39. 39.
    Schenck CH, Mahowald MW. A polysomnographic, neurologic, psychiatric and clinical outcome report on 70 consecutive cases with REM sleep behavior disorder (RBD): sustained clonzepam efficacy in 89.5% of 57 treated patients. Clev Clin J Med. 1990;57(Suppl):10–24.Google Scholar
  40. 40.
    Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003;4(4):281–4.PubMedCrossRefGoogle Scholar
  41. 41.
    Kunz D, Mahlberg R. A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder. J Sleep Res. 2010;19(4):591–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Gagnon JF, Postuma RB, Montplaisir J. Update on the pharmacology of REM sleep behavior disorder. Neurology. 2006;67(5):742–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Anderson KN, Shneerson JM. Drug treatment of REM sleep behavior disorder: the use of drug therapies other than clonazepam. J Clin Sleep Med. 2009;5(3):235–9.PubMedGoogle Scholar
  44. 44.
    Takeuchi N, Uchimura N, Hashizume Y, et al. Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci. 2001;55(3):267–9.PubMedCrossRefGoogle Scholar
  45. 45.•
    Gaig C, Iranzo A. Sleep-disordered breathing in neurodegenerative diseases. Curr Neurol Neurosci Rep. 2012;12(2):205–17.PubMedCrossRefGoogle Scholar
  46. 46.
    Iranzo A, Santamaria J, Tolosa E, et al. Long-term effect of CPAP in the treatment of nocturnal stridor in multiple system atrophy. Neurology. 2004;63:930–2.PubMedCrossRefGoogle Scholar
  47. 47.
    Vetrugno R, Liguori R, Cortelli P, et al. Sleep-related stridor due to dystonic vocal cord motion and neurogenic tachypnea/tachycardia in multiple system atrophy. Mov Disord. 2007;22(5):673–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Wenning GK, Tison F, Shlomo YB, et al. Multiple system atrophy: a review of 203 pathologically proven cases. Mov Disord. 1997;12:133–47.PubMedCrossRefGoogle Scholar
  49. 49.
    Ghorayeb I, Yekhlef F, Chrysostome Y, et al. Sleep disorders and their determinants in multiple system atrophy. J Neurol Neurosurg Psychiatry. 2002;72:798–800.PubMedCrossRefGoogle Scholar
  50. 50.
    Manni R, Morini R, Martignoni E, et al. A nocturnal sleep in multisystem atrophy with autonomic failure: polygraphic findings in ten patients. J Neurol. 1993;240:247–50.CrossRefGoogle Scholar
  51. 51.
    Iranzo A, Santamaria J, Tolosa E, et al. Continuous positive air pressure eliminates nocturnal stridor in multiple system atrophy. Lancet. 2000;356:1329–30.PubMedCrossRefGoogle Scholar
  52. 52.
    Glass GA, Josephs KA, Ahlskog JE. Respiratory insufficiency as the primary presenting symptom of multiple system atrophy. Arch Neurol. 2006;63:978–81.PubMedCrossRefGoogle Scholar
  53. 53.
    Uzawa A, Sakakibara R, Tamura N, et al. Laryngeal abductor paralysis can be a solitary manifestation of multiple system atrophy. J Neurol Neurosurg Psychiatry. 2005;76:1739–41.PubMedCrossRefGoogle Scholar
  54. 54.
    Munschauer FE, Loh L, Bannister R, et al. Abnormal respiration and sudden death during sleep in multiple system atrophy with autonomic failure. Neurology. 1990;40:677–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Shimohata T, Ozawa T, Nakayama H, et al. Frequency of nocturnal sudden death in patients with multiple system atrophy. J Neurol. 2008;255:1483–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Yamaguchi M, Arai K, Asahina M, et al. Laryngeal stridor in multiple system atrophy. Eur Neurol. 2003;49:154–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Iranzo A. Management of sleep-disordered breathing in multiple system atrophy. Sleep Med. 2005;6:297–300.PubMedCrossRefGoogle Scholar
  58. 58.
    Kuźniar TJ, Morgenthaler TI, Prakash UB, et al. Effects of continuous positive airway pressure on stridor in multiple system atrophy-sleep laryngoscopy. J Clin Sleep Med. 2009;5:65–7.PubMedGoogle Scholar
  59. 59.
    Louter M, Pelleboer RH, van den Broek GB, et al. Nocturnal stridor in multiple system atrophy. Ned Tijdschr Geneeskd. 2011;155(46):A3621.PubMedGoogle Scholar
  60. 60.
    Merlo IM, Ochinni A, Pacchetti C, et al. Not paralysis, but dystonia causes stridor in multiple system atrophy. Neurology. 2002;58:649–52.PubMedCrossRefGoogle Scholar
  61. 61.
    Benarroch EE, Schmeichel AM, Low PA, et al. Depletion of putative chemosensitive respiratory neurons in the ventral medullary surface in multiple system atrophy. Brain. 2007;130(Pt 2):469–75.PubMedCrossRefGoogle Scholar
  62. 62.
    Iranzo A. Sleep and breathing in multiple system atrophy. Curr Treat Opt Neurol. 2007;9(5):347–53.Google Scholar
  63. 63.
    Chokroverty S, Sachdeo R, Masdeu J. Autonomic dysfunction and sleep apnea in olivopontocerebellar degeneration. Arch Neurol. 1984;41(9):926–31.PubMedCrossRefGoogle Scholar
  64. 64.
    Cormican LJ, Higgins S, Davidson AC, et al. Multiple system atrophy presenting as central sleep apnoea. Eur Respir J. 2004;24(2):323–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Suzuki M, Saigusa H, Shibasaki K. Multiple system atrophy manifesting as complex sleep-disordered breathing. Auris Nasus Larynx. 2010;37:110–3.PubMedCrossRefGoogle Scholar
  66. 66.
    Shimohata T, Shinoda H, Nakayama H, et al. Daytime hypoxemia, sleep-disorder breathing, and laryngopharyngeal findings in multiple system atrophy. Arch Neurol. 2007;64:856–61.PubMedCrossRefGoogle Scholar
  67. 67.
    Vincken W, Gauthier S, Dollfuss R, et al. Involvement of upper-airway muscles in extrapyramidal disorders. A cause of airflow limitation. N Engl J Med. 1984;16:438–42.CrossRefGoogle Scholar
  68. 68.
    Ghorayeb I, Yekhlef F, Bioulac B, et al. Continuous positive airway pressure for sleep-related breathing disorders in multiple system atrophy: long term acceptance. Sleep Med. 2005;6:359–62.PubMedCrossRefGoogle Scholar
  69. 69.••
    Shimohata T, Tomita M, Nakayama H, et al. Floppy epiglottis as a contraindication of CPAP in patients with multiple system atrophy. Neurology. 2011;76:1841–2.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Clinical Neurosciences, Sleep Disorders CenterUniversità Vita-Salute San RaffaeleMilanItaly

Personalised recommendations