Background: The definition of rapid eye movement (REM) sleep behavior disorder (RBD) has varied over the years. Rapid eye movement sleep behavior disorder can be considered isolated or idiopathic or can occur in the context of other disorders, including trauma-associated sleep disorder (TSD) and overlap parasomnia. However, whether trauma in RBD carries any prognostic specificity is currently unknown. Study Objectives: To test the hypothesis that RBD secondary to trauma is less likely to result in the development of neurodegeneration compared to idiopathic RBD (iRBD) without trauma in the general population. Methods: A retrospective cohort study of 122 consecutive RBD patients (103 males) at two tertiary sleep clinics in Europe between 2005 and 2020 was studied. Patients were diagnosed as having iRBD by video polysomnography (vPSG) and had a semi-structured interview at presentation, including specifically eliciting any history of trauma. Patients with secondary RBD to recognized causes were excluded from the study. Patients with iRBD were categorized into three groups according to reported trauma history: (1) No history of trauma, (2) traumatic experience at least 12 months prior to RBD symptom onset, and (3) traumatic experience within 12 months of RBD symptom onset. Idiopathic RBD duration was defined as the interval between estimated onset of RBD symptoms and last hospital visit or death. Follow-up duration was defined as the interval between iRBD diagnosis and last hospital visit or death. Results: In a follow-up period of up to 18 years, no patient who experienced trauma within 12 months preceding their iRBD diagnosis received a diagnosis of a neurodegenerative disorder (n = 35), whereas 38% of patients without trauma within the 12 months of symptom onset developed a neurodegenerative illness. These patients were also significantly more likely to have a family history of α-synucleinopathy or tauopathy. Conclusions: The development of RBD within 12 months of experiencing a traumatic life event, indistinguishable clinically from iRBD, did not lead to phenoconversion to a neurodegenerative disorder even after 18 years (mean follow up 6 years). We suggest that a sub-type of RBD be established and classified as secondary RBD due to trauma. Additionally, we advocate that a thorough psychological and trauma history be undertaken in all patients presenting with dream enactment behaviors (DEB).

Department of Neurology University of Dundee Ninewells Hospital Dundee United Kingdom

Northumbria Centre for Sleep Research Northumbria University Newcastle United Kingdom

Sleep Research Unit Centre for Clinical Brain Sciences University of Edinburgh Edinburgh United Kingdom

The Department of Neurology and Clinical Sciences Charles University Prague Czechia

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Schenck CH, Mahowald MW. REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP. Sleep. (2002) 25:120–38. 10.1093/sleep/25.2.120 PubMed DOI

American Academy of Sleep Medicine . International Classification of Sleep Disorders, 3rd ed: Diagnostic and Coding Manual. Darien, IL: American Academy of Sleep Medicine; (2014).

Kang SH, Yoon IY, Lee SD, Han JW, Kim TH, Kim KW, et al. . Sleep behavior disorder in the Korean elderly population: prevalence and clinical characteristics. Sleep. (2013) 36:1147–52. 10.5665/sleep.2874 PubMed DOI PMC

Pujol M, Pujol J, Alonso T, Fuentes A, Pallerola M, Freixenet J, 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) 40:116–21. 10.1016/j.sleep.2017.07.021 PubMed DOI

Rodriguez CL, Jaimchariyatam N, Budur K. Rapid eye movement sleep behavior disorder: a review of the literature and update on current concepts. Chest. (2017) 152:650–62. 10.1016/j.chest.2017.03.015 PubMed DOI

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. 10.1111/j.1749-6632.2009.05115.x PubMed DOI PMC

McCann H, Stevens CH, Cartwright H, Halliday GM. α-Synucleinopathy phenotypes. Parkinsonism Relat Disord. (2014) 20:S62–7. 10.1016/S1353-8020(13)70017-8 PubMed DOI

Mysliwiec V, O'Reilly B, Polchinski J, Kwon HP, Germain A, Roth BJ. Trauma associated sleep disorder: a proposed parasomnia encompassing disruptive nocturnal behaviors, nightmares, and REM without atonia in trauma survivors. J Clin Sleep Med. (2014) 10:1143–8. 10.5664/jcsm.4120 PubMed DOI PMC

Feemster JC, Smith KL, McCarter SJ, St Louis EK. Trauma-associated sleep disorder: a posttraumatic stress/REM sleep behavior disorder mash-up? J Clin Sleep Med. (2019) 15:345–9. 10.5664/jcsm.7642 PubMed DOI PMC

Mysliwiec V, Brock MS, Creamer JL, O'Reilly BM, Germain A, Roth BJ. Trauma associated sleep disorder: a parasomnia induced by trauma. Sleep Med Rev. (2018) 37:94–104. 10.1016/j.smrv.2017.01.004 PubMed DOI

Fernández-Arcos A, Iranzo A, Serradell M, Gaig C, Santamaria J. The clinical phenotype of idiopathic rapid eye movement sleep behavior disorder at presentation: a study in 203 consecutive patients. Sleep. (2016) 39:121–32. 10.5665/sleep.5332 PubMed DOI PMC

World Medical Association . World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. (2013). 310:2191–4. 10.1001/jama.2013.281053 PubMed DOI

American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; (2013). 10.1176/appi.books.9780890425596 DOI

ICD-10_CM Official Guidelines for Coding and Reporting FY 2018 . (October 1, 2017–September 30, 2018). Available online at: https://www.cdc.gov/nchs/data/icd/10cmguidelines_fy2018_final.pdf (accessed March 1, 2020).

Berry RB, Brooks R, Gamaldo C, Harding SM, Lloyd RM, Quan SF, et al. . The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Version 2.4. Darien, IL: American Academy of Sleep Medicine; (2017).

Galbiati A, Carli G, Hensley M, Ferini-Strambi L. REM sleep behavior disorder and Alzheimer's disease: definitely no relationship? J Alzheimers Dis. (2018) 63:1–11. 10.3233/JAD-171164 PubMed DOI

Postuma RB, Iranzo A, Hu M, Högl B, Boeve BF, Manni R, et al. . Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain. (2019) 142:744–59. 10.1093/brain/awz030 PubMed DOI PMC

Galbiati A, Verga L, Giora E, Zucconi M, Ferini-Strambi L. The risk of neurodegeneration in REM sleep behavior disorder: a systematic review and meta-analysis of longitudinal studies. Sleep Med Rev. (2019) 43:37–46. 10.1016/j.smrv.2018.09.008 PubMed DOI

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) 14:744–8. 10.1016/j.sleep.2012.10.009 PubMed DOI

Germain A, Buysse DJ, Nofzinger E. Sleep-specific mechanisms underlying posttraumatic stress disorder: integrative review and neurobiological hypotheses. Sleep Med Rev. (2008) 12:185–95. 10.1016/j.smrv.2007.09.003 PubMed DOI PMC

Pawlyk AC, Jha SK, Brennan FX, Morrison AR, Ross RJ. A rodent model of sleep disturbances in posttraumatic stress disorder: the role of context after fear conditioning. Biol Psychiatry. (2005) 57:268–77. 10.1016/j.biopsych.2004.11.008 PubMed DOI

Jha SK, Brennan FX, Pawlyk AC, Ross RJ, Morrison AR. REM sleep: a sensitive index of fear conditioning in rats. Eur J Neurosci. (2005) 21:1077–80. 10.1111/j.1460-9568.2005.03920.x PubMed DOI

Engdahl BE, Eberly RE, Hurwitz TD, Mahowald MW, Blake J. Sleep in a community sample of elderly war veterans with and without posttraumatic stress disorder. Biol Psychiatry. (2000) 47:520–5. 10.1016/s0006-3223(99)00201-2 PubMed DOI

Hurwitz TD, Mahowald MW, Kuskowski M, Engdahl BE. Polysomnographic sleep is not clinically impaired in Vietnam combat veterans with chronic posttraumatic stress disorder. Biol Psychiatry. (1998) 44:1066–73. 10.1016/s0006-3223(98)00089-4 PubMed DOI

Clark RW, Boudoulas H, Schaal SF, Schmidt HS. Adrenergic hyperactivity and cardiac abnormality in primary disorders of sleep. Neurology. (1980) 30:113–9. 10.1212/wnl.30.2.113 PubMed DOI

Oudiette D, De Cock VC, Lavault S, Leu S, Vidailhet M, Arnulf I. Nonviolent elaborate behaviors may also occur in REM sleep behavior disorder. Neurology. (2009) 72:551–7. 10.1212/01.wnl.0000341936.78678.3a PubMed DOI

El-Solh AA. Management of nightmares in patients with posttraumatic stress disorder: current perspectives. Nat Sci Sleep. (2018) 10:409–20. 10.2147/NSS.S166089 PubMed DOI PMC

Nardo D, Högberg G, Jonsson C, Jacobsson H, Hällström T, Pagani M. Neurobiology of sleep disturbances in PTSD patients and traumatized controls: MRI and SPECT findings. Front Psychiatry. (2015) 6:134. 10.3389/fpsyt.2015.00134 PubMed DOI PMC

Williams LM, Kemp AH, Felmingham K, Barton M, Olivieri G, Peduto A, et al. . Trauma modulates amygdala and medial prefrontal responses to consciously attended fear. Neuroimage. (2006) 29:347–57. 10.1016/j.neuroimage.2005.03.047 PubMed DOI

Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A, Deisseroth K, et al. . Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature. (2012) 484:381–5. 10.1038/nature11028 PubMed DOI PMC

LeDoux JE, Iwata J, Cicchetti P, Reis DJ. Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear. J Neurosci. (1988) 8:2517–29. 10.1523/JNEUROSCI.08-07-02517.1988 PubMed DOI PMC

Tong J, Simpson K, Alvarez-Jimenez M, Bendall S. Talking about trauma in therapy: perspectives from young people with post-traumatic stress symptoms and first episode psychosis. Early Interv Psychiatry. (2019) 13:1236–44. 10.1111/eip.12761 PubMed DOI

Scottish Health Survey. (2019). Available online at: https://www.gov.scot/publications/scottish-health-survey-2019-volume-1-main-report/ (accessed May 12, 2021).

Iranzo A, Fairfoul G, Ayudhaya ACN, Serradell M, Gelpi E, Vilaseca I, 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) 20:203–12. 10.1016/S1474-4422(20)30449-X PubMed DOI

Dauvilliers Y, Postuma RB, Ferini-Strambi L, Arnulf I, Högl B, Manni R, et al. . Family history of idiopathic REM behavior disorder: a multicenter case-control study. Neurology. (2013) 80:2233–5. 10.1212/wnl.0b013e318296e967 PubMed DOI PMC

Liu Y, Zhang J, Lam SP, Zhou J, Yu MWM, Li SX, et al. . A case-control-family study of idiopathic rapid eye movement sleep behavior disorder. Ann Neurol. (2019) 85:582–92. 10.1002/ana.25435 PubMed DOI