549
Views
3
CrossRef citations to date
0
Altmetric
REVIEW

Considering REM Sleep Behavior Disorder in the Management of Parkinson’s Disease

ORCID Icon, , ORCID Icon, , ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon show all
Pages 333-352 | Received 09 Nov 2022, Accepted 25 Apr 2023, Published online: 05 May 2023

References

  • Matar E, McCarter SJ, St Louis EK, Lewis SJG. Current Concepts and Controversies in the Management of REM Sleep Behavior Disorder. Neurotherapeutics. 2021;18(1):107–123. doi:10.1007/s13311-020-00983-7
  • Dauvilliers Y, Schenck CH, Postuma RB, et al. REM sleep behaviour disorder. Nat Rev Dis Primers. 2018;4(1):19. doi:10.1038/s41572-018-0016-5
  • Iranzo A. The REM sleep circuit and how its impairment leads to REM sleep behavior disorder. Cell Tissue Res. 2018;373(1):245–266. doi:10.1007/s00441-018-2852-8
  • Iranzo A, Santamaria J, Tolosa E. The clinical and pathophysiological relevance of REM sleep behavior disorder in neurodegenerative diseases. Sleep Med Rev. 2009;13(6):385–401. doi:10.1016/j.smrv.2008.11.003
  • Haba-Rubio J, Marti-Soler H, Marques-Vidal P, et al. Prevalence and determinants of periodic limb movements in the general population: PLMS in the General Population. Ann Neurol. 2016;79(3):464–474. doi:10.1002/ana.24593
  • Pujol M, Pujol J, Alonso T, et al. Idiopathic REM sleep behavior disorder in the elderly Spanish community: a primary care center study with a two-stage design using video-polysomnography. Sleep Med. 2017;40:116–121. doi:10.1016/j.sleep.2017.07.021
  • Iranzo A, Santamaria J, Tolosa E. Idiopathic rapid eye movement sleep behaviour disorder: diagnosis, management, and the need for neuroprotective interventions. Lancet Neurol. 2016;15(4):405–419. doi:10.1016/S1474-4422(16)00057-0
  • Högl B, Arnulf I, Bergmann M, et al. Rapid eye movement sleep behaviour disorder: past, present, and future. J Sleep Res. 2022;31:4. doi:10.1111/jsr.13612
  • Fereshtehnejad SM, Zeighami Y, Dagher A, Postuma RB. Clinical criteria for subtyping Parkinson’s disease: biomarkers and longitudinal progression. Brain. 2017;140(7):1959–1976. doi:10.1093/brain/awx118
  • Marras C, Chaudhuri KR. Nonmotor features of ParkinsonParkinson’s disease subtypes. Mov Disord. 2016;31(8):1095–1102. doi:10.1002/mds.26510
  • 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 behavior disorder. Neurology. 1996;46(2):388–393. doi:10.1212/wnl.46.2.388
  • Braak H, Del Tredici K, Rüb U, de Vos RAI, Jansen Steur ENH, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197–211. doi:10.1016/s0197-4580(02
  • Valencia Garcia S, Brischoux F, Clément O, et al. Ventromedial medulla inhibitory neuron inactivation induces REM sleep without atonia and REM sleep behavior disorder. Nat Commun. 2018;9(1):504. doi:10.1038/s41467-017-02761-0
  • Braak H, Ghebremedhin E, Rüb U, Bratzke H, Del Tredici K. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res. 2004;318(1):121–134. doi:10.1007/s00441-004-0956-9
  • Hawkes CH, Del Tredici K, Braak H. Parkinson’s disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol. 2007;33(6):599–614. doi:10.1111/j.1365-2990.2007.00874.x
  • Van Den Berge N, Ulusoy A. Animal models of brain-first and body-first Parkinson’s disease. Neurobiol Dis. 2022;163:105599. doi:10.1016/j.nbd.2021.105599
  • Attems J, Jellinger KA. The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson’s disease. Neuropathol Appl Neurobiol. 2008;34(4):466–467. doi:10.1111/j.1365-2990.2008.00937.x
  • Jellinger KA. Is Braak staging valid for all types of Parkinson’s disease? J Neural Transm. 2019;126(4):423–431. doi:10.1007/s00702-018-1898-9
  • Borghammer P, Van Den Berge N. Brain-First versus Gut-First Parkinson’s Disease: a Hypothesis. JPD. 2019;9(s2):S281–S295. doi:10.3233/JPD-191721
  • Horsager J, Andersen KB, Knudsen K, et al. Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain. 2020;143(10):3077–3088. doi:10.1093/brain/awaa238
  • McKenna D, Peever J. Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder. Mov Disord. 2017;32(5):636–644. doi:10.1002/mds.27003
  • Leclair-Visonneau L, Clairembault T, Coron E, et al. REM sleep behavior disorder is related to enteric neuropathology in Parkinson disease. Neurology. 2017;89(15):1612–1618. doi:10.1212/WNL.0000000000004496
  • Postuma RB, Adler CH, Dugger BN, et al. REM sleep behavior disorder and neuropathology in Parkinson’s disease: RBD in PD. Mov Disord. 2015;30(10):1413–1417. doi:10.1002/mds.26347
  • Bohnen NI, Postuma RB. Body-first versus brain-first biological subtyping of Parkinson’s disease. Brain. 2020;143(10):2871–2873. doi:10.1093/brain/awaa293
  • Borghammer P. The α-Synuclein Origin and Connectome Model (SOC Model) of Parkinson’s Disease: explaining Motor Asymmetry, Non-Motor Phenotypes, and Cognitive Decline. JPD. 2021;11(2):455–474. doi:10.3233/JPD-202481
  • Oltra J, Uribe C, Segura B, et al. Brain atrophy pattern in de novo Parkinson’s disease with probable RBD associated with cognitive impairment. npj Parkinsons Dis. 2022;8(1):60. doi:10.1038/s41531-022-00326-7
  • Riboldi GM, Russo MJ, Pan L, Watkins K, Kang UJ. Dysautonomia and REM sleep behavior disorder contributions to progression of Parkinson’s disease phenotypes. npj Parkinsons Dis. 2022;8(1):110. doi:10.1038/s41531-022-00373-0
  • Fereshtehnejad SM, Romenets SR, Anang JBM, Latreille V, Gagnon JF, Postuma RB. New Clinical Subtypes of Parkinson Disease and Their Longitudinal Progression: a Prospective Cohort Comparison With Other Phenotypes. JAMA Neurol. 2015;72(8):863. doi:10.1001/jamaneurol.2015.0703
  • Fereshtehnejad SM, Postuma RB. Subtypes of Parkinson’s Disease: what Do They Tell Us About Disease Progression? Curr Neurol Neurosci Rep. 2017;17(4). doi:10.1007/s11910-017-0738-x
  • Zhang H, Iranzo A, Högl B, et al. Risk Factors for Phenoconversion in Rapid Eye Movement Sleep Behavior Disorder. Ann Neurol. 2022;91(3):404–416. doi:10.1002/ana.26298
  • 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;14(8):744–748. doi:10.1016/j.sleep.2012.10.009
  • de Natale ER, Wilson H, Politis M. Predictors of RBD progression and conversion to synucleinopathies. Curr Neurol Neurosci Rep. 2022;22(2):93–104. doi:10.1007/s11910-022-01171-0
  • Miglis MG, Adler CH, Antelmi E, et al. Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder. Lancet Neurol. 2021;20(8):671–684. doi:10.1016/S1474-4422(21)00176-9
  • Postuma RB, Iranzo A, Hu M, et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain. 2019;142(3):744–759. doi:10.1093/brain/awz030
  • Fereshtehnejad SM, Yao C, Pelletier A, Montplaisir JY, Gagnon JF, Postuma RB. Evolution of prodromal Parkinson’s disease and dementia with Lewy bodies: a prospective study. Brain. 2019;142(7):2051–2067. doi:10.1093/brain/awz111
  • Del Din S, Yarnall AJ, Barber TR, et al. Continuous Real-World Gait Monitoring in Idiopathic REM Sleep Behavior Disorder. J Parkinsons Dis. 2020;10(1):283–299. doi:10.3233/JPD-191773
  • Arora S, Baig F, Lo C, et al. Smartphone motor testing to distinguish idiopathic REM sleep behavior disorder, controls, and PD. Neurology. 2018;91(16):e1528–e1538. doi:10.1212/WNL.0000000000006366
  • Hanuška J, Rusz J, Bezdicek O, et al. Eye movements in idiopathic rapid eye movement sleep behaviour disorder: high antisaccade error rate reflects prefrontal cortex dysfunction. J Sleep Res. 2019;28(5):e12742. doi:10.1111/jsr.12742
  • Krupička R, Krýže P, Neťuková S, et al. Instrumental analysis of finger tapping reveals a novel early biomarker of parkinsonism in idiopathic rapid eye movement sleep behaviour disorder. Sleep Med. 2020;75:45–49. doi:10.1016/j.sleep.2020.07.019
  • Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson’s disease. Mov Disord. 2015;30(12):1600–1611. doi:10.1002/mds.26431
  • Iranzo A, Marrero-González P, Serradell M, Gaig C, Santamaria J, Vilaseca I. Significance of hyposmia in isolated REM sleep behavior disorder. J Neurol. 2021;268(3):963–966. doi:10.1007/s00415-020-10229-3
  • Miyamoto T, Miyamoto M. Odor identification predicts the transition of patients with isolated RBD: a retrospective study. Ann Clin Transl Neurol. 2022;9(8):1177–1185. doi:10.1002/acn3.51615
  • Postuma RB, Gagnon JF, Vendette M, Desjardins C, Montplaisir JY. Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder. Ann Neurol. 2011;69(5):811–818. doi:10.1002/ana.22282
  • Li Y, Zhang H, Mao W, et al. Visual dysfunction in patients with idiopathic rapid eye movement sleep behavior disorder. Neurosci Lett. 2019;709:134360. doi:10.1016/j.neulet.2019.134360
  • Yang ZJ, Wei J, Mao CJ, et al. Retinal nerve fiber layer thinning: a window into rapid eye movement sleep behavior disorders in Parkinson’s disease. Sleep Breath. 2016;20(4):1285–1292. doi:10.1007/s11325-016-1366-4
  • Ferini-Strambi L, Oertel W, Dauvilliers Y, et al. Autonomic symptoms in idiopathic REM behavior disorder: a multicentre case–control study. J Neurol. 2014;261(6):1112–1118. doi:10.1007/s00415-014-7317-8
  • Zitser J, During EH, Chiaro G, Miglis MG. Autonomic impairment as a potential biomarker in idiopathic REM-sleep-behavior disorder. Autonomic Neurosci. 2019;220:102553. doi:10.1016/j.autneu.2019.05.005
  • Postuma RB, Lanfranchi PA, Blais H, Gagnon JF, Montplaisir JY. Cardiac autonomic dysfunction in idiopathic REM sleep behavior disorder. Mov Disord. 2010;25(14):2304–2310. doi:10.1002/mds.23347
  • Yang JH, Choi SH, Lee MH, et al. Association of heart rate variability with REM sleep without atonia in idiopathic REM sleep behavior disorder. J Clin Sleep Med. 2021;17(3):461–469. doi:10.5664/JCSM.8934
  • McCarter SJ, Gehrking TL, St Louis EK, et al. Autonomic dysfunction and phenoconversion in idiopathic REM sleep behavior disorder. Clin Auton Res. 2020;30(3):207–213. doi:10.1007/s10286-020-00674-5
  • Bauckneht M, Chincarini A, De Carli F, et al. Presynaptic dopaminergic neuroimaging in REM sleep behavior disorder: a systematic review and meta-analysis. Sleep Med Rev. 2018;41:266–274. doi:10.1016/j.smrv.2018.04.001
  • Iranzo A, Santamaría J, Valldeoriola F, et al. Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder. Ann Neurol. 2017;82(3):419–428. doi:10.1002/ana.25026
  • Li Y, Kang W, Yang Q, et al. Predictive markers for early conversion of iRBD to neurodegenerative synucleinopathy diseases. Neurology. 2017;88(16):1493–1500. doi:10.1212/WNL.0000000000003838
  • Chahine LM, Brumm MC, Caspell-Garcia C, et al. Dopamine transporter imaging predicts clinically-defined α-synucleinopathy in REM sleep behavior disorder. Ann Clin Transl Neurol. 2021;8(1):201–212. doi:10.1002/acn3.51269
  • Arnaldi D, Chincarini A, Hu MT, et al. Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder. Brain. 2021;144(1):278–287. doi:10.1093/brain/awaa365
  • Arnaldi D, Famà F, Girtler N, et al. Rapid eye movement sleep behavior disorder: a proof-of-concept neuroprotection study for prodromal synucleinopathies. Eur J Neurol. 2021;28(4):1210–1217. doi:10.1111/ene.14664
  • Dang-Vu TT, Gagnon JF, Vendette M, Soucy JP, Postuma RB, Montplaisir J. Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder. Neurology. 2012;79(24):2302–2306. doi:10.1212/WNL.0b013e318278b658
  • Heller J, Brcina N, Dogan I, et al. Brain imaging findings in idiopathic REM sleep behavior disorder (RBD) – a systematic review on potential biomarkers for neurodegeneration. Sleep Med Rev. 2017;34:23–33. doi:10.1016/j.smrv.2016.06.006
  • Campabadal A, Segura B, Junque C, Iranzo A. Structural and functional magnetic resonance imaging in isolated REM sleep behavior disorder: a systematic review of studies using neuroimaging software. Sleep Med Rev. 2021;59:101495. doi:10.1016/j.smrv.2021.101495
  • Ota Y, Kanel P, Bohnen N. Imaging of sleep disorders in pre-Parkinsonian syndromes. Curr Opin Neurol. 2022;35(4):443–452. doi:10.1097/WCO.0000000000001084
  • Shi M, Sheng L, Stewart T, Zabetian CP, Zhang J. New windows into the brain: central nervous system-derived extracellular vesicles in blood. Prog Neurobiol. 2019;175:96–106. doi:10.1016/j.pneurobio.2019.01.005
  • Kluge A, Bunk J, Schaeffer E, et al. Detection of neuron-derived pathological α-synuclein in blood. Brain. 2022;145(9):3058–3071. doi:10.1093/brain/awac115
  • Stefani A, Iranzo A, Holzknecht E, et al. Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder. Brain. 2021;144(4):1118–1126. doi:10.1093/brain/awab005
  • Zitser J, Gibbons C, Miglis MG. The role of tissue biopsy as a biomarker in REM sleep behavior disorder. Sleep Med Rev. 2020;51:101283. doi:10.1016/j.smrv.2020.101283
  • Iranzo A, Fairfoul G, Ayudhaya ACN, et al. Detection of α-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study. Lancet Neurol. 2021;20(3):203–212. doi:10.1016/S1474-4422(20)30449-X
  • Thaler A, Bregman N, Gurevich T, et al. Parkinson’s disease phenotype is influenced by the severity of the mutations in the GBA gene. Parkinsonism Relat Disord. 2018;55:45–49. doi:10.1016/j.parkreldis.2018.05.009
  • Krohn L, Ruskey JA, Rudakou U, et al. GBA variants in REM sleep behavior disorder: a multicenter study. Neurology. 2020;95(8):e1008–e1016. doi:10.1212/WNL.0000000000010042
  • Honeycutt L, Montplaisir JY, Gagnon JF, et al. Glucocerebrosidase mutations and phenoconversion of REM sleep behavior disorder to parkinsonism and dementia. Parkinsonism Relat Disord. 2019;65:230–233. doi:10.1016/j.parkreldis.2019.04.016
  • Krohn L, Wu RYJ, Heilbron K, et al. Fine‐Mapping of SNCA in Rapid Eye Movement Sleep Behavior Disorder and Overt Synucleinopathies. Ann Neurol. 2020;87(4):584–598. doi:10.1002/ana.25687
  • Ye G, Li Y, Zhou L, et al. Predictors of Conversion to α-Synucleinopathy Diseases in Idiopathic Rapid Eye Movement Sleep Behavior Disorder. J Parkinsons Dis. 2020;10(4):1443–1455. doi:10.3233/JPD-202243
  • Terzaghi M, Toscano G, Casoni F, et al. Assessment of cognitive profile as a prodromal marker of the evolution of REM sleep Behavior Disorder. Sleep. 2019. doi:10.1093/sleep/zsz103
  • Vendette M, Montplaisir J, Gosselin N, et al. Brain perfusion anomalies in rapid eye movement sleep behavior disorder with mild cognitive impairment. Mov Disord. 2012;27(10):1255–1261. doi:10.1002/mds.25034
  • Jozwiak N, Postuma RB, Montplaisir J, et al. REM Sleep Behavior Disorder and Cognitive Impairment in Parkinson’s Disease. Sleep. 2017;40:8. doi:10.1093/sleep/zsx101
  • Marchand DG, Montplaisir J, Postuma RB, Rahayel S, Gagnon JF. Detecting the Cognitive Prodrome of Dementia with Lewy Bodies: a Prospective Study of REM Sleep Behavior Disorder. Sleep. 2017;40:1. doi:10.1093/sleep/zsw014
  • Gagnon JF, Vendette M, Postuma RB, et al. Mild cognitive impairment in rapid eye movement sleep behavior disorder and Parkinson’s disease. Ann Neurol. 2009;66(1):39–47. doi:10.1002/ana.21680
  • McCarter SJ, Tabatabai GM, Jong HY, et al. REM sleep atonia loss distinguishes synucleinopathy in older adults with cognitive impairment. Neurology. 2020;94(1):e15–e29. doi:10.1212/WNL.0000000000008694
  • Rahayel S, Postuma RB, Montplaisir J, et al. Cortical and subcortical gray matter bases of cognitive deficits in REM sleep behavior disorder. Neurology. 2018;90(20):e1759–e1770. doi:10.1212/WNL.0000000000005523
  • Rahayel S, Postuma RB, Montplaisir J, et al. A Prodromal Brain-Clinical Pattern of Cognition in Synucleinopathies. Ann Neurol. 2021;89(2):341–357. doi:10.1002/ana.25962
  • Rémillard-Pelchat D, Rahayel S, Gaubert M, et al. Comprehensive Analysis of Brain Volume in REM Sleep Behavior Disorder with Mild Cognitive Impairment. J Parkinsons Dis. 2022;12(1):229–241. doi:10.3233/JPD-212691
  • Postuma RB, Iranzo A, Hogl B, et al. Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study. Ann Neurol. 2015;77(5):830–839. doi:10.1002/ana.24385
  • Génier Marchand D, Postuma RB, Escudier F, et al. How does dementia with Lewy bodies start? Prodromal cognitive changes in REM sleep behavior disorder. Ann Neurol. 2018;83(5):1016–1026. doi:10.1002/ana.25239
  • Génier Marchand D, Montplaisir J, Postuma RB, Rahayel S, Gagnon JF. Detecting the Cognitive Prodrome of Dementia with Lewy Bodies: a Prospective Study of REM Sleep Behavior Disorder. Sleep. 2017;40:1. doi:10.1093/sleep/zsw014
  • Heinzel S, Berg D, Gasser T, et al. Update of the MDS research criteria for prodromal Parkinson’s disease. Mov Disord. 2019;34(10):1464–1470. doi:10.1002/mds.27802
  • Gagnon JF, Bertrand JA, Génier Marchand D. Cognition in rapid eye movement sleep behavior disorder. Front Neurol. 2012;3:82. doi:10.3389/fneur.2012.00082
  • Ferini-Strambi L, Fasiello E, Sforza M, Salsone M, Galbiati A. Neuropsychological, electrophysiological, and neuroimaging biomarkers for REM behavior disorder. Expert Rev Neurother. 2019;19(11):1069–1087. doi:10.1080/14737175.2019.1640603
  • Figorilli M, Lanza G, Congiu P, et al. Neurophysiological Aspects of REM Sleep Behavior Disorder (RBD): a Narrative Review. Brain Sci. 2021;11(12):1588. doi:10.3390/brainsci11121588
  • Valomon A, Riedner BA, Jones SG, et al. A high-density electroencephalography study reveals abnormal sleep homeostasis in patients with rapid eye movement sleep behavior disorder. Sci Rep. 2021;11(1):4758. doi:10.1038/s41598-021-83980-w
  • Ferri R, Rundo F, Silvani A, et al. REM Sleep EEG Instability in REM Sleep Behavior Disorder and Clonazepam Effects. Sleep. 2017;40:8. doi:10.1093/sleep/zsx080
  • Ferri R, Zucconi M, Marelli S, Plazzi G, Schenck CH, Ferini-Strambi L. Effects of long-term use of clonazepam on nonrapid eye movement sleep patterns in rapid eye movement sleep behavior disorder. Sleep Med. 2013;14(5):399–406. doi:10.1016/j.sleep.2013.01.007
  • Shin C, Park H, Lee WW, Kim HJ, Kim HJ, Jeon B. Clonazepam for probable REM sleep behavior disorder in Parkinson’s disease: a randomized placebo-controlled trial. J Neurol Sci. 2019;401:81–86. doi:10.1016/j.jns.2019.04.029
  • Hadi F, Agah E, Tavanbakhsh S, et al. Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson’s disease and sleep disorders: a randomized, double-blind trial. Neurol Sci. 2022;43(10):6141–6148. doi:10.1007/s10072-022-06188-4
  • Yan J, Liu A, Huang J, et al. Pharmacological Interventions for REM Sleep Behavior Disorder in Parkinson’s Disease: a Systematic Review. Front Aging Neurosci. 2021;13:709878. doi:10.3389/fnagi.2021.709878
  • Que Z, Zheng C, Zhao Z, et al. The treatment efficacy of pharmacotherapies for rapid eye movement sleep behavior disorder with polysomnography evaluation: a systematic review and meta-analysis. Heliyon. 2022;8(11):e11425. doi:10.1016/j.heliyon.2022.e11425
  • Brooks PL, Peever JH. Impaired GABA and glycine transmission triggers cardinal features of rapid eye movement sleep behavior disorder in mice. J Neurosci. 2011;31(19):7111–7121. doi:10.1523/JNEUROSCI.0347-11.2011
  • Parrino L, Ferri R, Bruni O, Terzano MG. Cyclic alternating pattern (CAP): the marker of sleep instability. Sleep Med Rev. 2012;16(1):27–45. doi:10.1016/j.smrv.2011.02.003
  • Kutlu A, Işeri P, Selekler M, Benbir G, Karadeniz D. Cyclic alternating pattern analysis in REM sleep behavior disorder. Sleep and Breathing. 2013;17(1):209–215. doi:10.1007/s11325-012-0675-5
  • Melpignano A, Parrino L, Santamaria J, et al. Isolated rapid eye movement sleep behavior disorder and cyclic alternating pattern: is sleep microstructure a predictive parameter of neurodegeneration? Sleep. 2019;42(10):zsz142. doi:10.1093/sleep/zsz142
  • O’Reilly C, Godin I, Montplaisir J, Nielsen T. REM sleep behaviour disorder is associated with lower fast and higher slow sleep spindle densities. J Sleep Res. 2015;24(6):593–601. doi:10.1111/jsr.12309
  • Christensen JAE, Kempfner J, Zoetmulder M, et al. Decreased sleep spindle density in patients with idiopathic REM sleep behavior disorder and patients with Parkinson’s disease. Clin Neurophysiol. 2014;125(3):512–519. doi:10.1016/j.clinph.2013.08.013
  • Ruffini G, Ibañez D, Castellano M, et al. Deep Learning With EEG Spectrograms in Rapid Eye Movement Behavior Disorder. Front Neurol. 2019;10:806. doi:10.3389/fneur.2019.00806
  • Gong S-Y, Shen Y, Gu H-Y, et al. Generalized EEG Slowing Across Phasic REM Sleep, Not Subjective RBD Severity, Predicts Neurodegeneration in Idiopathic RBD. Nat Sci Sleep. 2022;14:407–418. doi:10.2147/NSS.S354063
  • Lanza G, DelRosso LM, Ferri R. Sleep and homeostatic control of plasticity. Handb Clin Neurol. 2022;184:53–72. doi:10.1016/B978-0-12-819410-2.00004-7
  • Fisicaro F, Lanza G, Cantone M, et al. Clinical and Electrophysiological Hints to TMS in De Novo Patients with Parkinson’s Disease and Progressive Supranuclear Palsy. J Pers Med. 2020;10(4):E274. doi:10.3390/jpm10040274
  • Cantone M, Lanza G, Ranieri F, Opie GM, Terranova C. Editorial: non-invasive Brain Stimulation in the Study and Modulation of Metaplasticity in Neurological Disorders. Front Neurol. 2021;12:721906. doi:10.3389/fneur.2021.721906
  • Di Lazzaro V, Bella R, Benussi A, et al. Diagnostic contribution and therapeutic perspectives of transcranial magnetic stimulation in dementia. Clin Neurophysiol. 2021;132(10):2568–2607. doi:10.1016/j.clinph.2021.05.035
  • Nardone R, Bergmann J, Kunz A, et al. Cortical afferent inhibition is reduced in patients with idiopathic REM sleep behavior disorder and cognitive impairment: a TMS study. Sleep Med. 2012;13(7):919–925. doi:10.1016/j.sleep.2012.03.009
  • Nardone R, Bergmann J, Brigo F, et al. Functional evaluation of central cholinergic circuits in patients with Parkinson’s disease and REM sleep behavior disorder: a TMS study. J Neural Transm. 2013;120(3):413–422. doi:10.1007/s00702-012-0888-6
  • Lanza G, Aricò D, Lanuzza B, et al. Facilitatory/inhibitory intracortical imbalance in REM sleep behavior disorder: early electrophysiological marker of neurodegeneration? Sleep. 2020;43(3):zsz242. doi:10.1093/sleep/zsz242
  • Peever J, Luppi PH, Montplaisir J. Breakdown in REM sleep circuitry underlies REM sleep behavior disorder. Trends Neurosci. 2014;37(5):279–288. doi:10.1016/j.tins.2014.02.009
  • Lanza G, Cosentino FII, Lanuzza B, et al. Reduced Intracortical Facilitation to TMS in Both Isolated REM Sleep Behavior Disorder (RBD) and Early Parkinson’s Disease with RBD. J Clin Med. 2022;11(9):2291. doi:10.3390/jcm11092291
  • Bhattacharya A, Kamble N, Yadav R, Stezin A, Pal PK. Abnormal Intracortical Functions in Parkinson’s Disease with Rapid Eye Movement Sleep Behaviour Disorder. Can J Neurol Sci. 2022;49(5):672–677. doi:10.1017/cjn.2021.206
  • Lanza G, Fisicaro F, Cantone M, et al. Repetitive transcranial magnetic stimulation in primary sleep disorders. Sleep Med Rev. 2023;67:101735. doi:10.1016/j.smrv.2022.101735
  • Magnano I, Pes GM, Cabboi MP, et al. Comparison of brainstem reflex recordings and evoked potentials with clinical and MRI data to assess brainstem dysfunction in multiple sclerosis: a short-term follow-up. Neurol Sci. 2016;37(9):1457–1465. doi:10.1007/s10072-016-2604-z
  • de Natale ER, Ginatempo F, Laccu I, et al. Vestibular Evoked Myogenic Potentials Are Abnormal in Idiopathic REM Sleep Behavior Disorder. Front Neurol. 2018;9:911. doi:10.3389/fneur.2018.00911
  • de Natale ER, Ginatempo F, Paulus KS, et al. Abnormalities of vestibular-evoked myogenic potentials in idiopathic Parkinson’s disease are associated with clinical evidence of brainstem involvement. Neurol Sci. 2015;36(6):995–1001. doi:10.1007/s10072-014-2054-4
  • Puligheddu M, Figorilli M, Serra A, et al. REM Sleep without atonia correlates with abnormal vestibular-evoked myogenic potentials in isolated REM sleep behavior disorder. Sleep. 2019;42(9):zsz128. doi:10.1093/sleep/zsz128
  • Xie WY, Shen Y, Chen Y, et al. REM sleep without atonia and vestibular-evoked myogenic potentials: clinical brainstem dysfunction in early-stage Parkinson’s disease and isolated REM sleep behavior disorder. Sleep Med. 2022;89:122–129. doi:10.1016/j.sleep.2021.12.004
  • Stefani A, Holzknecht E, Högl B. Clinical neurophysiology of REM parasomnias. Handb Clin Neurol. 2019;161:381–396. doi:10.1016/B978-0-444-64142-7.00062-X
  • Perkins JE, Janzen A, Bernhard FP, et al. Saccade, Pupil, and Blink Responses in Rapid Eye Movement Sleep Behavior Disorder. Mov Disord. 2021;36(7):1720–1726. doi:10.1002/mds.28585
  • Weise D, Pargac C, Pelz JO, Rumpf JJ, Fricke C, Classen J. Assessing blink reflex circuits by three different afferent routes in Parkinson’s disease. Clin Neurophysiol. 2019;130(4):582–587. doi:10.1016/j.clinph.2018.12.009
  • Aygün D, Ertaş Fİ, Gündüz A, Benbir Şenel G, Karadeniz D, Kızıltan M. The role of pedunculopontine nucleus in isolated REM sleep behavior disorder and REM sleep without atonia. Parkinsonism Relat Disord. 2021;84:68–73. doi:10.1016/j.parkreldis.2021.01.025
  • Frauscher B, Nomura T, Duerr S, et al. Investigation of autonomic function in idiopathic REM sleep behavior disorder. J Neurol. 2012;259(6):1056–1061. doi:10.1007/s00415-011-6298-0
  • Pilotto A, Romagnolo A, Tuazon JA, et al. Orthostatic hypotension and REM sleep behaviour disorder: impact on clinical outcomes in α-synucleinopathies. J Neurol Neurosurg Psychiatry. 2019;90(11):1257–1263. doi:10.1136/jnnp-2019-320846
  • Jung KY, Cho JH, Ko D, et al. Increased Corticomuscular Coherence in Idiopathic REM Sleep Behavior Disorder. Front Neurol. 2012;3:60. doi:10.3389/fneur.2012.00060
  • Choi GS, Yun JY, Hwang S, et al. Can Corticomuscular Coherence Differentiate between REM Sleep Behavior Disorder with or without Parkinsonism? J Clin Med. 2021;10(23):5585. doi:10.3390/jcm10235585
  • Raggi A, Manconi M, Consonni M, et al. Event-related potentials in idiopathic rapid eye movements sleep behaviour disorder. Clin Neurophysiol. 2007;118(3):669–675. doi:10.1016/j.clinph.2006.11.011
  • Raggi A, Lanza G, Ferri RA. Review on P300 in Obsessive-Compulsive Disorder. Front Psychiatry. 2021;12:751215. doi:10.3389/fpsyt.2021.751215
  • Raggi A, Lanza G, Ferri R. Auditory mismatch negativity in bipolar disorder: a focused review. Rev Neurosci. 2022;33(1):17–30. doi:10.1515/revneuro-2021-0010
  • Gaudreault PO, Gagnon JF, Montplaisir J, et al. Abnormal occipital event-related potentials in Parkinson’s disease with concomitant REM sleep behavior disorder. Parkinsonism Relat Disord. 2013;19(2):212–217. doi:10.1016/j.parkreldis.2012.10.006
  • Iranzo A, Santamaría J, Rye DB, et al. Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD. Neurology. 2005;65(2):247–252. doi:10.1212/01.wnl.0000168864.97813.e0
  • Antelmi E, Pizza F, Donadio V, et al. Biomarkers for REM sleep behavior disorder in idiopathic and narcoleptic patients. Ann Clin Transl Neurol. 2019;6(9):1872–1876. doi:10.1002/acn3.50833
  • Berg D, Borghammer P, Fereshtehnejad SM, et al. Prodromal Parkinson disease subtypes - key to understanding heterogeneity. Nat Rev Neurol. 2021;17(6):349–361. doi:10.1038/s41582-021-00486-9
  • Gilat M, Marshall NS, Testelmans D, Buyse B, Lewis SJG. A critical review of the pharmacological treatment of REM sleep behavior disorder in adults: time for more and larger randomized placebo-controlled trials. J Neurol. 2022;269(1):125–148. doi:10.1007/s00415-020-10353-0
  • de Almeida CMO, Pachito DV, Sobreira-Neto MA, Tumas V, Eckeli AL. Pharmacological treatment for REM sleep behavior disorder in Parkinson disease and related conditions: a scoping review. J Neurol Sci. 2018;393:63–68. doi:10.1016/j.jns.2018.08.008
  • Li SX, Lam SP, Zhang J, et al. A prospective, naturalistic follow-up study of treatment outcomes with clonazepam in rapid eye movement sleep behavior disorder. Sleep Med. 2016;21:114–120. doi:10.1016/j.sleep.2015.12.020
  • Ferri R, Marelli S, Ferini-Strambi L, et al. An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder. Sleep Med. 2013;14(1):24–29. doi:10.1016/j.sleep.2012.09.009
  • McCarter SJ, Boswell CL, St Louis EK, et al. Treatment outcomes in REM sleep behavior disorder. Sleep Med. 2013;14(3):237–242. doi:10.1016/j.sleep.2012.09.018
  • Kunz D, Bes F. Melatonin as a therapy in rem sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on rem-sleep regulation. Mov Disorders. 1999;14(3):507–511. doi:10.1002/1531-8257(199905)14:3<507::
  • Boeve B. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003;4(4):281–284. doi:10.1016/S1389-9457(03)00072-8
  • Taximaimaiti R, Luo X, Wang XP. Pharmacological and Non-pharmacological Treatments of Sleep Disorders in Parkinson’s Disease. Curr Neuropharmacol. 2021;19(12):2233–2249. doi:10.2174/1570159X19666210517115706
  • Gilat M, Coeytaux jackson A, Marshall NS, et al. Melatonin for Rapid Eye Movement Sleep Behavior Disorder in Parkinson’s disease: a Randomised Controlled Trial. Mov Disorders. 2020;35(2):344–349. doi:10.1002/mds.27886
  • Kashihara K, Nomura T, Maeda T, et al. Beneficial Effects of Ramelteon on Rapid Eye Movement Sleep Behavior Disorder Associated with Parkinson’s Disease - Results of a Multicenter Open Trial. Intern Med. 2016;55(3):231–236. doi:10.2169/internalmedicine.55.5464
  • Nomura T, Kawase S, Watanabe Y, Nakashima K. Use of ramelteon for the treatment of secondary REM sleep behavior disorder. Intern Med. 2013;52(18):2123–2126. doi:10.2169/internalmedicine.52.9179
  • Dusek P, Busková J, Růzicka E, et al. Effects of ropinirole prolonged-release on sleep disturbances and daytime sleepiness in Parkinson disease. Clin Neuropharmacol. 2010;33(4):186–190. doi:10.1097/WNF.0b013e3181e71166
  • Wang Y, Yang Y, Wu H, Lan D, Chen Y, Zhao Z. Effects of Rotigotine on REM Sleep Behavior Disorder in Parkinson Disease. J Clin Sleep Med. 2016;12(10):1403–1409. doi:10.5664/jcsm.6200
  • Wilson SM, Wurst MG, Whatley MF, Daniels RN. Classics in Chemical Neuroscience: pramipexole. ACS Chem Neurosci. 2020;11(17):2506–2512. doi:10.1021/acschemneuro.0c00332
  • Schmidt MH, Koshal VB, Schmidt HS. Use of pramipexole in REM sleep behavior disorder: results from a case series. Sleep Med. 2006;7(5):418–423. doi:10.1016/j.sleep.2006.03.018
  • Kumru H, Iranzo A, Carrasco E, et al. Lack of effects of pramipexole on REM sleep behavior disorder in Parkinson disease. Sleep. 2008;31(10):1418–1421.
  • Trenkwalder C, Kies B, Rudzinska M, et al. Rotigotine effects on early morning motor function and sleep in Parkinson’s disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord. 2011;26(1):90–99. doi:10.1002/mds.23441
  • Di Giacopo R, Fasano A, Quaranta D, Della marca G, Bove F, Bentivoglio AR. Rivastigmine as alternative treatment for refractory REM behavior disorder in Parkinson’s disease. Mov Disord. 2012;27(4):559–561. doi:10.1002/mds.24909
  • Brunetti V, Losurdo A, Testani E, et al. Rivastigmine for refractory REM behavior disorder in mild cognitive impairment. Curr Alzheimer Res. 2014;11(3):267–273. doi:10.2174/1567205011666140302195648
  • Ringman JM, Simmons JH. Treatment of REM sleep behavior disorder with donepezil: a report of three cases. Neurology. 2000;55(6):870–871. doi:10.1212/wnl.55.6.870
  • Larsson V, Aarsland D, Ballard C, Minthon L, Londos E. The effect of memantine on sleep behaviour in dementia with Lewy bodies and Parkinson’s disease dementia. Int J Geriatr Psychiatry. 2010;25(10):1030–1038. doi:10.1002/gps.2506
  • Chagas MHN, Eckeli AL, Zuardi AW, et al. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson’s disease patients: a case series. J Clin Pharm Ther. 2014;39(5):564–566. doi:10.1111/jcpt.12179
  • 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):235–239.
  • Bamford CR. Carbamazepine in REM sleep behavior disorder. Sleep. 1993;16(1):33–34.
  • Abenza Abildúa MJ, Miralles Martinez A, Arpa Gutiérrez FJ, et al. Conditions associated with REM sleep behaviour disorder: description of a hospital series. Neurologia. 2019;34(3):159–164. doi:10.1016/j.nrl.2016.11.011
  • Keir LHM, Breen DP. New awakenings: current understanding of sleep dysfunction and its treatment in Parkinson’s disease. J Neurol. 2020;267(1):288–294. doi:10.1007/s00415-019-09651-z
  • Meloni M, Figorilli M, Carta M, et al. Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson’s disease. Sleep Breath. 2022;26(3):1023–1031. doi:10.1007/s11325-021-02417-w
  • Shinno H, Kamei M, Nakamura Y, Inami Y, Horiguchi J. Successful treatment with Yi-Gan San for rapid eye movement sleep behavior disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(7):1749–1751. doi:10.1016/j.pnpbp.2008.06.015
  • Kunz D, Stotz S, Bes F. Treatment of isolated REM sleep behavior disorder using melatonin as a chronobiotic. J Pineal Res. 2021;71(2):e12759. doi:10.1111/jpi.12759
  • Cammisuli DM, Ceravolo R, Bonuccelli U. Non-pharmacological interventions for Parkinson’s disease mild cognitive impairment: future directions for research. Neural Regen Res. 2020;15(9):1650–1651. doi:10.4103/1673-5374.276329
  • Cristini J, Weiss M, De Las Heras B, et al. The effects of exercise on sleep quality in persons with Parkinson’s disease: a systematic review with meta-analysis. Sleep Med Rev. 2021;55:101384. doi:10.1016/j.smrv.2020.101384
  • McCarter SJ, Boeve BF, Graff-Radford NR, Silber MH, St Louis EK. Neuroprotection in idiopathic REM sleep behavior disorder: a role for exercise? Sleep. 2019;42(6):zsz064. doi:10.1093/sleep/zsz064
  • Hughes KC, Gao X, Molsberry S, Valeri L, Schwarzschild MA, Ascherio A. Physical activity and prodromal features of Parkinson disease. Neurology. 2019;93(23):e2157–e2169. doi:10.1212/WNL.0000000000008567
  • Frazzitta G, Maestri R, Ferrazzoli D, et al. Multidisciplinary intensive rehabilitation treatment improves sleep quality in Parkinson’s disease. J Clin Mov Disord. 2015;2:11. doi:10.1186/s40734-015-0020-9
  • Memon AA, Coleman JJ, Amara AW. Effects of exercise on sleep in neurodegenerative disease. Neurobiol Dis. 2020;140:104859. doi:10.1016/j.nbd.2020.104859
  • Howell MJ, Arneson PA, Schenck CH. A novel therapy for REM sleep behavior disorder (RBD). J Clin Sleep Med. 2011;7(6):639–644A. doi:10.5664/jcsm.1470
  • Zuzuárregui JRP, During EH. Sleep Issues in Parkinson’s Disease and Their Management. Neurotherapeutics. 2020;17(4):1480–1494. doi:10.1007/s13311-020-00938-y
  • Pereira EA, Muthusamy KA, De Pennington N, Joint CA, Aziz TZ. Deep brain stimulation of the pedunculopontine nucleus in Parkinson’s disease. Preliminary experience at Oxford. Br J Neurosurg. 2008;22:S41–44. doi:10.1080/02688690802448335
  • Stefani A, Lozano AM, Peppe A, et al. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain. 2007;130(Pt 6):1596–1607. doi:10.1093/brain/awl346
  • Chambers NE, Lanza K, Bishop C. Pedunculopontine Nucleus Degeneration Contributes to Both Motor and Non-Motor Symptoms of Parkinson’s Disease. Front Pharmacol. 2019;10:1494. doi:10.3389/fphar.2019.01494