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Background: Isolated rapid-eye-movement (REM) sleep behaviour disorder (IRBD) can be part of the prodromal stage of the α-synucleinopathies Parkinson's disease and dementia with Lewy bodies. Real-time quaking-induced conversion (RT-QuIC) analysis of CSF has high sensitivity and specificity for the detection of misfolded α-synuclein in patients with Parkinson's disease and dementia with Lewy bodies. We investigated whether RT-QuIC could detect α-synuclein in the CSF of patients with IRBD and be used as a biomarker of prodromal α-synucleinopathy., Methods: In this longitudinal observational study, CSF samples were obtained by lumbar puncture from patients with video polysomnography-confirmed IRBD recruited at a specialised sleep disorders centre in Barcelona, Spain, and from controls free of neurological disease. CSF samples were stored until analysed using RT-QuIC. After lumbar puncture, participants were assessed clinically for neurological status every 3-12 months. Rates of neurological disease-free survival were estimated using the Kaplan-Meier method. Disease-free survival rates were assessed from the date of lumbar puncture to the date of diagnosis of any neurodegenerative disease, or to the last follow-up visit for censored observations., Findings: 52 patients with IRBD and 40 healthy controls matched for age (p=0·20), sex (p=0·15), and duration of follow-up (p=0·27) underwent lumbar puncture between March 23, 2008, and July 16, 2017. The CSF α-synuclein RT-QuIC assay was positive in 47 (90%) patients with IRBD and in four (10%) controls, resulting in a sensitivity of 90·4% (95% CI 79·4-95·8) and a specificity of 90·0% (95% CI 76·9-96·0). Mean follow-up from lumbar puncture until the end of the study (July 31, 2020) was 7·1 years (SD 2·8) in patients with IRBD and 7·7 years (2·9) in controls. During follow-up, 32 (62%) patients were diagnosed with Parkinson's disease or dementia with Lewy bodies a mean 3·4 years (SD 2·6) after lumbar puncture, of whom 31 (97%) were α-synuclein positive at baseline. Kaplan-Meier analysis showed that patients with IRBD who were α-synuclein negative had lower risk for developing Parkinson's disease or dementia with Lewy bodies at 2, 4, 6, 8, and 10 years of follow-up than patients with IRBD who were α-synuclein positive (log-rank test p=0·028; hazard ratio 0·143, 95% CI 0·019-1·063). During follow-up, none of the controls developed an α-synucleinopathy. Kaplan-Meier analysis showed that participants who were α-synuclein negative (ie, five patients with IRBD plus 36 controls) had lower risk of developing Parkinson's disease or dementia with Lewy bodies at 2, 4, 6, 8 and 10 years after lumbar puncture than participants who were α-synuclein positive (ie, 47 patients with IRBD plus four controls; log-rank test p<0·0001; hazard ratio 0·024, 95% CI 0·003-0·177)., Interpretation: In patients with IRBD, RT-QuIC detects misfolded α-synuclein in the CSF with both sensitivity and specificity of 90%, and α-synuclein positivity was associated with increased risk of subsequent diagnosis of Parkinson's disease or dementia with Lewy bodies. Detection of α-synuclein in the CSF represents a potential prodromal marker of Parkinson's disease and dementia with Lewy bodies. If these findings are replicated in additional cohorts, detection of CSF α-synuclein by RT-QuIC could be used to enrich IRBD cohorts in neuroprotective trials, particularly when assessing interventions that target α-synuclein., Funding: Department of Health and Social Care Policy Research Programme, the Scottish Government, and the Weston Brain Institute., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Rapid eye movement behaviour disorder (RBD) is a parasomnia in which there is loss of muscle atonia during rapid eye movement (REM) sleep, resulting in dream enactment. The aims of this study were to determine the prevalence of obstructive sleep apnoea (OSA) in RBD patients and determine whether continuous positive airway pressure (CPAP) therapy improved RBD symptoms in patients with concomitant RBD and OSA., Methods: A questionnaire was mailed to 120 patients identified from a tertiary sleep centre with RBD meeting full International Classification for Sleep Disorders-3 (ICSD-3) criteria. Patients were diagnosed as having OSA if they had an apnoea-hypopnea index (AHI) ≥ 5. The questionnaire focused on CPAP-use, compliance and complications. Standard statistical analysis was undertaken using SPSS (v.21, IBM)., Results: One hundred and seven of the potential participants (89.2%) had an OSA diagnosis. Out of 72 who responded to the questionnaire, (60%) 27 patients were using CPAP therapy. CPAP therapy improved RBD symptoms in 45.8% of this group. Despite this positive response to treatment in nearly half of CPAP-users, there was no significant difference in subjective or objective CPAP compliance between those who reported RBD improvement and those who did not. Subjective compliance with CPAP was over-reported, with mean usage being 7.17 ± 1.7 h per night compared to objective mean compliance of 5.71 ± 1.7., Conclusions: OSA is a very common co-morbidity of RBD. CPAP therapy might improve self-reported RBD symptoms further, in addition to standard RBD treatment. However, further research into its topic is necessary.

Study Objectives: REM sleep behavior disorder (RBD) is a parasomnia in which normal muscle atonia of REM sleep is lost. The aim of this study was to confirm if diagnostic delay exists in RBD and identify any contributing factors., Methods: A database was compiled of 49 patients with RBD seen at a tertiary referral center from 2005 to 2011 by retrospective review of referral letters and polysomnographic (PSG) reports. Patients with comorbid narcolepsy were excluded. A questionnaire was sent to investigate diagnostic delay, management, and comorbidities., Results: Mean diagnostic delay was 8.7 ± 11 (median 4.5, IQR 1.75-11.75) years in 30 questionnaire responders. Common reasons for diagnostic delay included belief that symptoms were not serious enough to consult a doctor (59%), mild or infrequent occurrence of sleep behavior (56%), belief that symptoms may resolve (47%), and lack of knowledge of treatment options (47%). The bed partner was an important influence, with the decision to seek medical attention being made jointly by the patient and partner in 47%., Conclusions: This study has demonstrated the existence of significant diagnostic delay in RBD, mainly due to lack of understanding of the disorder and its treatment by patients and members of the medical profession.