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Sleep Dysfunction in Multiple System Atrophy

  • SLEEP DISORDERS (S CHOKROVERTY, SECTION EDITOR)
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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.

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References and Recommended Reading

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

  1. Ubhi K, Low P, Masliah E. Multiple system atrophy: a clinical and neuropathological perspective. Trends Neurosci. 2011;34(11):581–90.

    Article  PubMed  CAS  Google Scholar 

  2. Colosimo C. Nonmotor presentations of multiple system atrophy. Nat Rev Neurol. 2011;7(5):295–8.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  5. Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71:670–6.

    Article  PubMed  CAS  Google Scholar 

  6. Wenning GK, Colosimo C, Geser F, et al. Multiple system atrophy. Lancet Neurol. 2004;3:93–103.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  8. Plazzi G, Corsini R, Provini F, et al. REM sleep behavior disorders in multiple system atrophy. Neurology. 1997;48:1094–7.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  11. Köllensperger M, Geser F, Seppi K, et al. Red flags for multiple system atrophy. Mov Disord. 2008;23(8):1093–9.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  20. Arnulf I. Excessive daytime sleepiness in parkinsonism. Sleep Med Rev. 2005;9(3):185–200.

    Article  PubMed  Google Scholar 

  21. Benarroch EE, Schmeichel AM, Sandroni P, et al. Involvement of hypocretin neurons in multiple system atrophy. Acta Neuropathol. 2007;113:75–80.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  23. Drouot X, Moutereau S, Nguyen JP, et al. Low levels of ventricular CSF orexin/hypocretin in advanced PD. Neurology. 2003;61:540–3.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  42. Gagnon JF, Postuma RB, Montplaisir J. Update on the pharmacology of REM sleep behavior disorder. Neurology. 2006;67(5):742–7.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  44. Takeuchi N, Uchimura N, Hashizume Y, et al. Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci. 2001;55(3):267–9.

    Article  PubMed  CAS  Google Scholar 

  45. Gaig C, Iranzo A. Sleep-disordered breathing in neurodegenerative diseases. Curr Neurol Neurosci Rep. 2012;12(2):205–17.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  52. Glass GA, Josephs KA, Ahlskog JE. Respiratory insufficiency as the primary presenting symptom of multiple system atrophy. Arch Neurol. 2006;63:978–81.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  56. Yamaguchi M, Arai K, Asahina M, et al. Laryngeal stridor in multiple system atrophy. Eur Neurol. 2003;49:154–9.

    Article  PubMed  Google Scholar 

  57. Iranzo A. Management of sleep-disordered breathing in multiple system atrophy. Sleep Med. 2005;6:297–300.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  59. Louter M, Pelleboer RH, van den Broek GB, et al. Nocturnal stridor in multiple system atrophy. Ned Tijdschr Geneeskd. 2011;155(46):A3621.

    PubMed  Google Scholar 

  60. Merlo IM, Ochinni A, Pacchetti C, et al. Not paralysis, but dystonia causes stridor in multiple system atrophy. Neurology. 2002;58:649–52.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  62. Iranzo A. Sleep and breathing in multiple system atrophy. Curr Treat Opt Neurol. 2007;9(5):347–53.

    Google Scholar 

  63. Chokroverty S, Sachdeo R, Masdeu J. Autonomic dysfunction and sleep apnea in olivopontocerebellar degeneration. Arch Neurol. 1984;41(9):926–31.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  65. Suzuki M, Saigusa H, Shibasaki K. Multiple system atrophy manifesting as complex sleep-disordered breathing. Auris Nasus Larynx. 2010;37:110–3.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

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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.

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Correspondence to Luigi Ferini-Strambi MD, PhD.

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Ferini-Strambi, L., Marelli, S. Sleep Dysfunction in Multiple System Atrophy. Curr Treat Options Neurol 14, 464–473 (2012). https://doi.org/10.1007/s11940-012-0189-2

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