Impact of rapid eye movement sleep behavior disorder and autonomic disorders on Parkinson's disease: a review

ABSTRACT

Parkinson's disease (PD) has heterogeneous clinical manifestations and prognoses. It is accompanied by a group of motor and non-motor symptoms ranging from independence to total disability, limiting work and personal care activities. Currently, disease subtype markers for informing prognosis remain elusive. However, some studies have reported an association between rapid eye movement (REM) sleep behavior disorder (RBD) and faster motor and non-motor symptom progression, including autonomic dysfunction and cognitive decline. Moreover, since autonomic dysfunction has been described in idiopathic forms of RBD, and they share some central regulatory pathways, it remains unclear whether they have a primary association or if they are more severe in patients with PD and RBD, and thus are a disease subtype marker. This article aimed at critically reviewing the literature on the controversies about the prevalence of RBD in PD, the higher incidence of PD non-motor symptoms associated with RBD, the evidence of faster motor worsening in parkinsonian patients with this parasomnia, and the main pathophysiological hypotheses that support these findings.

RESUMO

A doença de Parkinson (DP) apresenta variadas manifestações clínicas e distintos prognósticos. É caracterizada por um conjunto de sintomas motores e não motores que podem variar desde um quadro de independência até a completa incapacidade laborativa e de cuidados pessoais. Até o momento, não está claro quais seriam os marcadores de subtipos da doença que poderiam alertar para formas de prognóstico. Porém existem alguns estudos que mostram que a presença do transtorno comportamental do sono REM pode estar associada à progressão mais rápida dos sintomas motores e não motores, como disfunção autonômica e declínio cognitivo. Questiona-se ainda se a disautonomia está primariamente associada ao transtorno do sono REM, já que são relatadas nas formas idiopáticas deste transtorno de sono e compartilham alguns núcleos reguladores centrais. Ou se são mais graves nos pacientes com diagnóstico de DP e transtorno comportamental do sono REM, marcando assim um subtipo da doença. Esta revisão teve como objetivo revisar criticamente os principais estudos publicados envolvendo as controvérsias sobre a prevalência do transtorno comportamental do sono REM na DP, a maior incidência de sintomas não motores da DP associados ao transtorno do sono REM, as evidências de piora motora mais rápida nos pacientes parkinsonianos que apresentam este transtorno do sono e as principais hipóteses fisiopatológicas que justificam esses achados.

Keywords:

Parkinson Disease - REM Sleep Behavior Disorder - Autonomic Nervous System Diseases - Pathology - Epidemiology

Palavras-chave:

Doença de Parkinson - Transtorno do Comportamento do Sono REM - Doenças do Sistema Nervoso Autônomo - Patologia - Epidemiologia

Authors’ contributions:

PO: participated in the planning, execution, and preparation of the manuscript. FC: advisor and supervisor of this review.

Publication History

Received: 23 April 2020

Accepted: 25 June 2020

Article published online:
04 July 2023

• References

• 1 Aygun D, Turkel Y, Onar MK, Sunter T. Clinical REM sleep behavior disorder and motor subtypes in Parkinson's disease: a questionnaire-based study. Clin Neurol Neurosurg. 2014 Apr;119:54-8. https://doi.org/10.1016/j.clineuro.2014.01.011
• 2 Pagano G, De Micco R, Yousaf T, Wilson H, Chandra A, Politis M. REM behavior disorder predicts motor progression and cognitive decline in Parkinson disease. Neurology. 2018 Sep;91(10):e894-e905. https://doi.org/10.1212/WNL.20200173202001736134
• 3 Baig F, Kelly MJ, Lawton MA, Ruffmann C, Rolinski M, Klein JC, et al. Impulse control disorders in Parkinson and RBD: A longitudinal study of severity. Neurology. 2019 Aug;93(7):e675-e687. https://doi.org/10.1212/WNL.20200173202001737942
• 4 Liu Y, Zhu XY, Zhang XJ, Kuo SH, Ondo WG, Wu YC. Clinical features of Parkinson's disease with and without rapid eye movement sleep behavior disorder. Transl Neurodegener. 2017 Dec;6:35. https://doi.org/10.1186/s40035-017-0105-5
• 5 Mahajan A, Rosenthal LS, Gamaldo C, Salas RE, Pontone GM, McCoy A, et al. REM sleep behavior and motor findings in Parkinson's disease: a cross-sectional analysis. Tremor Other Hyperkinet Mov (N Y). 2014 Jun;4:245. https://doi.org/10.7916/D84B2ZDF
• 6 Frauscher B, Nomura T, Duerr S, Ehrmann L, Gschliesser V, Wenning GK, et al. Investigation of autonomic function in idiopathic REM sleep behavior disorder. J Neurol. 2012 Jun;259(6):1056-61. https://doi.org/10.1007/s00415-011-6298-0
• 7 Ferini-Strambi L, Oertel W, Dauvilliers Y, Postuma RB, Marelli S, Iranzo A, et al. Autonomic symptoms in idiopathic REM behavior disorder: A multicentre case-control study. J Neurol. 2014 Jun;261(6):1112-8. https://doi.org/10.1007/s00415-014-7317-8
• 8 Janković M, Svetel M, Kostić V. Frequency of REM sleep behavior disorders in patients with Parkinson's disease. Vojnosanit Pregl. 2015 May;72(5):442-6. https://doi.org/10.2298/vsp130501006j
• 9 Munhoz RP, Moro A, Silveira-Moriyama L, Teive HA. Non-motor signs in Parkinson's disease: a review. Arq Neuropsiquiatr. 2015 May;73(5):454-62. https://doi.org/10.1590/0004-282X20150029
• 10 Högl B, Stefani A. REM sleep behavior disorder (RBD): Update on diagnosis and treatment. Somnologie (Berl). 2017;21(Suppl 1):1-8. https://doi.org/10.1007/s11818-016-0048-6
• 11 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 Jan;1184:15-54. https://doi.org/10.1111/j.1749-6632.2009.05115.x
• 12 Fraigne JJ, Torontali ZA, Snow MB, Peever JH. REM sleep at its core - circuits, neurotransmitters, and pathophysiology. Front Neurol. 2015 May;6:123. https://doi.org/10.3389/fneur.2015.00123
• 13 Fantini ML, Ferini-Strambi L, Montplaisir J. Idiopathic REM sleep behavior disorder: Toward a better nosologic definition. Neurology. 2005 Mar;64(5):780-6. https://doi.org/10.1212/01.WNL.0000152878.79429.00
• 14 Postuma RB, Lanfranchi PA, Blais H, Gagnon JF, Montplaisir JY. Cardiac autonomic dysfunction in idiopathic REM sleep behavior disorder. Mov Disord. 2010 Oct;25(14):2304-10. https://doi.org/10.1002/mds.23347
• 15 Sorensen GL, Mehlsen J, Jennum P. Reduced sympathetic activity in idiopathic rapid-eye-movement sleep behavior disorder and Parkinson's disease. Auton Neurosci. 2013 Dec;179(1-2):138-41. https://doi.org/10.1016/j.autneu.2013.08.067
• 16 Lee H, Cho YW, Kim HA. The severity and pattern of autonomic dysfunction in idiopathic rapid eye movement sleep behavior disorder. Mov Disord. 2015 Nov;30(13):1843-8. https://doi.org/10.1002/mds.26416
• 17 Aguirre-Mardones C, Iranzo A, Vilas D, Serradell M, Gaig C, Santamaria J, et al. Prevalence and timeline of nonmotor symptoms in idiopathic rapid eye movement sleep behavior disorder. J Neurol. 2015 Jun;262(6):1568-78. https://doi.org/10.1007/s00415-015-7742-3
• 18 Bedard MA, Aghourian M, Legault-Denis C, Postuma RB, Soucy JP, Gagnon JF, et al. Brain cholinergic alterations in idiopathic REM sleep behaviour disorder: a PET imaging study with (18)F-FEOBV. Sleep Med. 2019 Jun;58:35-41. https://doi.org/10.1016/j.sleep.2018.12.020
• 19 Zitser J, During EH, Chiaro G, Miglis MG. Autonomic impairment as a potential biomarker in idiopathic REM-sleep-behavior disorder. Auton Neurosci. 2019 Sep;220:102553. https://doi.org/10.1016/j.autneu.2019.05.005
• 20 Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 2013 Aug;14(8):744-8. https://doi.org/10.1016/j.sleep.2012.10.009
• 21 Kim YE, Jeon BS. Clinical implication of REM sleep behavior disorder in Parkinson's disease. J Parkinsons Dis. 2014;4(2):237-44. https://doi.org/10.3233/JPD-130293
• 22 Zhang X, Sun X, Wang J, Tang L, Xie A. Prevalence of rapid eye movement sleep behavior disorder (RBD) in Parkinson's disease: a meta and meta-regression analysis. Neurol Sci. 2017 Jan;38(1):163-70. https://doi.org/10.1007/s10072-016-2744-1
• 23 Munhoz RP, Teive HA. REM sleep behaviour disorder: how useful is it for the differential diagnosis of parkinsonism? Clin Neurol Neurosurg. 2014 Dec;127:71-4. https://doi.org/10.1016/j.clineuro.2014.09.014
• 24 Kim YE, Yang HJ, Yun JY, Kim HJ, Lee JY, Jeon BS. REM sleep behavior disorder in Parkinson disease: association with abnormal ocular motor findings. Parkinsonism Relat Disord. 2014 Apr;20(4):444-6. https://doi.org/10.1016/j.parkreldis.2013.12.003
• 25 Alatriste-Booth V, Rodríguez-Violante M, Camacho-Ordoñez A, Cervantes-Arriaga A. Prevalence and correlates of sleep disorders in Parkinson's disease: a polysomnographic study. Arq Neuropsiquiatr. 2015 Mar;73(3):241-5. https://doi.org/10.1590/0004-282X20140228
• 26 Swallow DM, Lawton MA, Grosset KA, Malek N, Smith CR, Bajaj NP, et al. Variation in recent onset parkinson's disease: implications for prodromal detection. J Parkinsons Dis. 2016 Mar;6(2):289-300. https://doi.org/10.3233/JPD-150741
• 27 Chahine LM, Xie SX, Simuni T, Tran B, Postuma R, Amara A, et al. Longitudinal changes in cognition in early Parkinson's disease patients with REM sleep behavior disorder. Parkinsonism Relat Disord. 2016 Jun;27:102-6. https://doi.org/10.1016/j.parkreldis.2016.03.006
• 28 Suzuki K, Okuma Y, Uchiyama T, Miyamoto M, Sakakibara R, Shimo Y, et al. Impact of sleep-related symptoms on clinical motor subtypes and disability in Parkinson's disease: a multicentre cross-sectional study. J Neurol Neurosurg Psychiatry. 2017 Nov;88(11):953-9. https://doi.org/10.1136/jnnp-2017-316136
• 29 Zhang J, Xu CY, Liu J. Meta-analysis on the prevalence of REM sleep behavior disorder symptoms in Parkinson's disease. BMC Neurol. 2017 Feb;17:23. https://doi.org/10.1186/s12883-017-0795-4
• 30 Duarte Folle A, Paul KC, Bronstein JM, Keener AM, Ritz B. Clinical progression in Parkinson's disease with features of REM sleep behavior disorder: a population-based longitudinal study. Parkinsonism Relat Disord. 2019 May;62:105-11. https://doi.org/10.1016/j.parkreldis.2019.01.018
• 31 Postuma RB, Montplaisir J, Lanfranchi P, Blais H, Rompre S, Colombo R, et al. Cardiac autonomic denervation in Parkinson's disease is linked to REM sleep behavior disorder. Mov Disord. 2011 Jul;26(8):1529-33. https://doi.org/10.1002/mds.23677
• 32 Fantini ML, Macedo L, Zibetti M, Sarchioto M, Vidal T, Pereira B, et al. Increased risk of impulse control symptoms in Parkinson's disease with REM sleep behaviour disorder. J Neurol Neurosurg Psychiatry. 2015 Feb;86(2):174-9. https://doi.org/10.1136/jnnp-2014-307904
• 33 Cui SS, Du JJ, Fu R, Lin YQ, Huang P, He YC, et al. Prevalence and risk factors for depression and anxiety in Chinese patients with Parkinson disease. BMC Geriatr. 2017 Nov;17:270. https://doi.org/10.1186/s12877-017-0666-2
• 34 Jozwiak N, Postuma RB, Montplaisir J, Latreille V, Panisset M, Chouinard S, et al. REM sleep behavior disorder and cognitive impairment in Parkinson's disease. Sleep. 2017 Aug;40(8):zsx101. https://doi.org/10.1093/sleep/zsx101
• 35 Kang SH, Yoon IY, Lee SD, Han JW, Kim TH, Kim KW. REM sleep behavior disorder in the Korean elderly population: prevalence and clinical characteristics. Sleep. 2013 Aug;36(8):1147-52. https://doi.org/10.5665/sleep.2874
• 36 Kim Y, Kim YE, Park EO, Shin CW, Kim HJ, Jeon B. REM sleep behavior disorder portends poor prognosis in Parkinson's disease: A systematic review. J Clin Neurosci. 2018 Jan;47:6-13. https://doi.org/10.1016/j.jocn.2017.09.019
• 37 Liu H, Ou R, Wei Q, Hou Y, Cao B, Zhao B, et al. Rapid eye movement behavior disorder in drug-naive patients with Parkinson's disease. J Clin Neurosci. 2019 Jan;59:254-8. https://doi.org/10.1016/j.jocn.2018.07.007
• 38 Banks SJ, Bayram E, Shan G, LaBelle DR, Bluett B. Non-motor predictors of freezing of gait in Parkinson's disease. Gait Posture. 2019 Feb;68:311-6. https://doi.org/10.1016/j.gaitpost.2018.12.009
• 39 Bargiotas P, Ntafouli M, Lachenmayer ML, Krack P, Schupbach WMM, Bassetti CLA. Apathy in Parkinson's disease with REM sleep behavior disorder. J Neurol Sci. 2019 Apr;399:194-8. https://doi.org/10.1016/j.jns.2019.02.028
• 40 Pilotto A, Romagnolo A, Tuazon JA, Vizcarra JA, Marsili L, Zibetti M, et al. Orthostatic hypotension and REM sleep behaviour disorder: impact on clinical outcomes in alpha-synucleinopathies. J Neurol Neurosurg Psychiatry. 2019 Nov;90(11):1257-63. https://doi.org/10.1136/jnnp-2019-320846
• 41 Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. Mar-Apr 2003;24(2):197-211. https://doi.org/10.1016/s0197-4580(02)00065-9
• 42 Iranzo A, Fernandez-Arcos A, Tolosa E, Serradell M, Molinuevo JL, Valldeoriola F, et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: Study in 174 patients. PLoS One. 2014 Feb;9(2):e89741. https://doi.org/10.1371/journal.pone.0089741
• 43 Beissner F, Meissner K, Bar KJ, Napadow V. The autonomic brain: an activation likelihood estimation meta-analysis for central processing of autonomic function. J Neurosci. 2013 Jun;33(25):10503-11. https://doi.org/10.1523/JNEUROSCI.1103-13.2013
• 44 Fenster RJ, Lebois LAM, Ressler KJ, Suh J. Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man. Nat Rev Neurosci. 2018 Sep;19(9):535-51. https://doi.org/10.1038/s41583-018-0039-7
• 45 Miglis MG. Autonomic dysfunction in primary sleep disorders. Sleep Med. 2016 Mar;19:40-9. https://doi.org/10.1016/j.sleep.2015.10.001
• 46 McDonald C, Winge K, Burn DJ. Lower urinary tract symptoms in Parkinson's disease: Prevalence, aetiology and management. Parkinsonism Relat Disord. 2017 Feb;35:8-16. https://doi.org/10.1016/j.parkreldis.2016.10.024
• 47 Palma JA, Gomez-Esteban JC, Norcliffe-Kaufmann L, Martinez J, Tijero B, Berganzo K, et al. Orthostatic hypotension in Parkinson disease: how much you fall or how low you go? Mov Disord. 2015 Apr;30(5):639-45. https://doi.org/10.1002/mds.26079
• 48 Yu QJ, Yu SY, Zuo LJ, Lian TH, Hu Y, Wang RD, et al. Parkinson disease with constipation: clinical features and relevant factors. Sci Rep. 2018 Jan;8(1):567. https://doi.org/10.1038/s41598-017-16790-8
• 49 Srivanitchapoom P, Pandey S, Hallett M. Drooling in Parkinson's disease: a review. Parkinsonism Relat Disord. 2014 Nov;20(11):1109-18. https://doi.org/10.1016/j.parkreldis.2014.08.013
• 50 Bronner G, Vodusek DB. Management of sexual dysfunction in Parkinson's disease. Ther Adv Neurol Disord. 2011 Nov;4(6):375-83. https://doi.org/10.1177/1756285611411504
• 51 Nomura T, Inoue Y, Kagimura T, Nakashima K. Clinical significance of REM sleep behavior disorder in Parkinson's disease. Sleep Med. 2013 Feb;14(2):131-5. https://doi.org/10.1016/j.sleep.2012.10.011
• 52 Anang JB, Gagnon JF, Bertrand JA, Romenets SR, Latreille V, Panisset M, et al. Predictors of dementia in Parkinson disease: a prospective cohort study. Neurology. 2014 Sep;83(14):1253-60. https://doi.org/10.1212/WNL.20200173202001730842
• 53 Kim JS, Park HE, Oh YS, Lee SH, Park JW, Son BC, et al. Orthostatic hypotension and cardiac sympathetic denervation in Parkinson disease patients with REM sleep behavioral disorder. J Neurol Sci. 2016 Mar 15;362:59-63. https://doi.org/10.1016/j.jns.2016.01.020
• 54 Jin H, Zhang JR, Shen Y, Liu CF. Clinical significance of REM sleep behavior disorders and other non-motor symptoms of Parkinsonism. Neurosci Bull. 2017 Oct;33(5):576-84. https://doi.org/10.1007/s12264-017-0164-8
• 55 Kim JS, Park HE, Park IS, Oh YS, Ryu DW, Song IU, et al. Normal ‘heart’ in Parkinson's disease: is this a distinct clinical phenotype? Eur J Neurol. 2017 Feb;24(2):349-56. https://doi.org/10.1111/ene.13206
• 56 Fereshtehnejad SM, Postuma RB. Subtypes of Parkinson's disease: what do they tell us about disease progression? Curr Neurol Neurosci Rep. 2017 Apr;17(4):34. https://doi.org/10.1007/s11910-017-0738-x
• 57 Al-Qassabi A, Pelletier A, Fereshtehnejad SM, Postuma RB. Autonomic sweat responses in REM sleep behavior disorder and Parkinsonism. J Parkinsons Dis. 2018;8(3):463-8. https://doi.org/10.3233/JPD-181357
• 58 Kadastik-Eerme L, Rosenthal M, Paju T, Muldmaa M, Taba P. Health-related quality of life in Parkinson's disease: a cross-sectional study focusing on non-motor symptoms. Health Qual Life Outcomes. 2015 Jun;13:83. https://doi.org/10.1186/s12955-015-0281-x
• 59 Mendoza-Velásquez JJ, Flores-Vázquez JF, Barrón-Velázquez E, Sosa-Ortiz AL, Illigens BW, Siepmann T. Autonomic dysfunction in alpha-synucleinopathies. Front Neurol. 2019 Apr;10:363. https://doi.org/10.3389/fneur.2019.00363
• 60 De Pablo-Fernandez E, Tur C, Revesz T, Lees AJ, Holton JL, Warner TT. Association of autonomic dysfunction with disease progression and survival in Parkinson disease. JAMA Neurol. 2017 Aug;74(8):970-6. https://doi.org/10.1001/jamaneurol.2017.1125