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Background and Objectives: Isolated REM sleep behavior disorder (iRBD) is strongly associated with synucleinopathies. Previous iRBD cohort studies have primarily focused on older (>50 years), male-predominant cohorts. Risk of phenoconversion in women and younger adults remains unclear. The study aimed to determine clinical features associated with conversion to a defined neurodegenerative disorder in women and men with iRBD., Methods: One hundred eighty-six women and 186 men with iRBD were matched by polysomnography month. Baseline clinical variables and subsequent neurodegenerative outcomes were abstracted by chart review. Kaplan-Meier curves assessed conversion rates. Cox proportional hazards modeling evaluated factors associated with phenoconversion risk., Results: Age at iRBD diagnosis was younger in women compared with men (54.9 vs 62.5 years, p < 0.01). Forty-eight patients (12.9%), including 18 women (9.7%) and 30 men (16.1%), phenoconverted during a median follow-up of 6.0 years. Conversion rates were lower in antidepressant users and patients with chronic pain or psychiatric comorbidity while rates were higher in those with vascular comorbidity. Only age at diagnosis (HR 1.09, 95% CI 1.06-1.13) was associated with phenoconversion after adjusting for RBD symptom duration; sex; antidepressant use; and psychiatric, chronic pain, and vascular comorbidities., Discussion: Age at diagnosis was independently associated with phenoconversion risk in women and men with iRBD.

Background: Currently, no standard scale has been validated to assess overall severity of RBD symptoms in the home environment. We aimed to evaluate the psychometric properties of the International RBD Severity Scale (IRBD-SSS), a new tool designed by the International RBD Study Group., Methods: Two versions of the IRBD-SSS were created, one for the patient (IRBD-SSS-PT) and another for the bedpartner (IRBD-SSS-BP), both consisting of 3 components, namely vocalizations, body movements and injury, with a fourth component (patient version only) evaluating dream content. To score each dimension, the frequency and severity/impact of behaviors during the previous month are multiplied. Psychometric properties of the IRBD-SSS were assessed, including reproducibility., Results: A total of 188 subjects including n = 132 RBD patients (n = 94 isolated RBD and n = 38 symptomatic RBD) and n = 52 bedpartners were enrolled from eight Sleep centers across France and Italy. Participants completed the scale at baseline and after one week. Acceptability of the scale was excellent in patients (97%) and bedpartners (98%). Internal consistency was acceptable for IRBD-SSS-PT (Cronbach α = 0.75) while slightly low for IRBD-SSS-BP (Cronbach α = 0.49). Concurrent validity was good for both patient (r = 0.70;p < 0.001, see Figure) and bedpartner (r = 0.69;p < 0.001) IRBD-SSS. Reproducibility was high for IRBD-SSS-PT (Lin's coefficient of agreement = 0.85 [0.81;0.90]) and good for the IRBD-SSS-BP (0.79 [0.68;0.90] (p < 0.001)., Conclusions: Both the patient and bedpartner versions of the IRBD-SSS showed excellent acceptability, acceptable internal consistency, good external validity and high reproducibility. IRBD-SSS is a useful tool to test the severity of RBD symptoms in clinical settings and clinical trials., Trial Registration: NCT04071899., Competing Interests: Declarations Conflicts of interest Authors have no financial or non-financial interests that are directly or indirectly related to the work submitted for publication. Ethical standard statement All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by local ethical board (CPP Ouest II)., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: The recurrence of obstructive sleep apnoea (OSA) after positive airway pressure (PAP) therapy termination has physiological consequences that may increase cardiovascular (CV) risk. We aimed to determine whether PAP termination is associated with an increased incidence of major adverse CV events (MACE) compared with adherent PAP continuation., Methods: Data from the Pays de la Loire Sleep Cohort were linked to the French national health insurance database to identify incident MACE (composite outcome of mortality, stroke and cardiac diseases), and CV active drug (lipid-lowering, antihypertensive and antiplatelet drugs, beta-blockers) adherence (medication possession ratio ≥80%). The association of PAP termination with MACE was evaluated using a time-dependent survival Cox model, with adjustment for confounders including CV active drug status., Results: After a median follow-up of 8 years, 969 of 4188 included patients (median age 58 years, 69.6% men) experienced MACE, 1485 had terminated PAP while 2703 continued PAP with at least 4 hours/night use. 38% of patients were adherent to all CV drugs in the PAP continuation group versus 28% in the PAP termination group (p<0.0001). After adjustment for confounders, PAP termination was associated with an increased risk of MACE (HR (95% CI): 1.39 (1.20 to 1.62); p<0.0001). PAP termination was not associated with incident heart failure and coronary artery disease., Conclusions: In this multicentre clinical-based cohort involving 4188 patients with OSA, PAP termination compared with adherent PAP continuation was associated with an increased risk of MACE. More research is needed to determine whether support programmes on PAP adherence could improve CV outcomes., Competing Interests: Competing interests: FGag declares receipt of personal fees from AIR LIQUIDE SANTE, INSPIRE, BIOPROJET, RESMED and SEFAM outside the submitted work; payment for presentations from PHILIPS RESPIRONICS, JAZZ PHARMACEUTICAL, BIOPROJET, CIDELEC and RESMED, non-financial support from ASTEN SANTE outside the submitted work. WT received support from ASTEN for attending scientific meetings and payment from AstraZeneca for lectures. SL has declared links of interest with Bioprojet, Idorsia, Vifor Pharma France (consultant), Resmed, Philips, Bioprojet, Jazz Pharmaceuticals, Cidelec, SOS Oxygène, Vitalaire, Zambon (speaker’s fees), ISIS Médical, Bioprojet, Resmed, SOS Oxygène (invitation to scientific meetings) and Bioserenity France (paid employee from 2019 to 2021). CL reports payment or presentations from RESMED, outside the submitted work. AS has recently been hired by SEFAM and has had links with interest with SOS Oxygène, Philips Respironics, Nukute, Nyxah and Cidelec. The other authors have no interests to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Objectives: The body-first Parkinson's disease (PD) hypothesis suggests initial gut Lewy body pathology initially propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels, a disease course presumed to likely occur in PD with rapid eye movement sleep behavior disorder (RBD). We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by non-rapid eye movement (NREM) sleep and wakefulness polysomnographic markers., Methods: In a study involving 43 patients with PD who underwent clinical examination, rectosigmoidoscopy, and polysomnography, we detected PASH on colonic biopsies using whole-mount immunostaining. We performed a visual semi-quantitative analysis of NREM sleep and wake electroencephalography (EEG), confirmed it with automated quantification of spindle and slow wave features of NREM sleep, and the wake dominant frequency, and then determined probable Arizona PD stage classifications based on sleep and wake EEG features., Results: The visual analysis aligned with the automated quantified spindle characteristics and the wake dominant frequency. Altered NREM sleep and wake parameters correlated with markers of PD severity, colonic PASH, and RBD diagnosis. Colonic PASH frequency also increased in parallel to probable Arizona PD stage classifications., Conclusions: Colonic PASH is strongly associated with widespread brain sleep and wake dysfunction, suggesting an extensive diffusion of the pathologic process in PD. Visual and automated analyses of polysomnography signals provide useful markers to gauge covert brain dysfunction in PD., Clinical Trial: Name: SYNAPark, URL: https://clinicaltrials.gov/study/NCT01748409, registration: NCT01748409., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Accurate diagnosis of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is crucial due to its injury potential and neurological prognosis. We aimed to analyze visual and automated REM sleep without atonia (RSWA) diagnostic thresholds applicable in varying clinical presentations in a contemporary cohort of patients with iRBD using submentalis (SM) and individual bilateral flexor digitorum superficialis (FDS) and anterior tibialis electromyography limb recordings during polysomnography., Methods: We analyzed RSWA in 20 patients with iRBD and 20 age-, REM-, apnea-hypopnea index-matched controls between 2017 and 2022 for phasic burst durations, density of phasic, tonic, and "any" muscle activity (number of 3-second mini-epochs containing phasic or tonic muscle activity divided by the total number of REM sleep 3-second mini-epochs), and automated Ferri REM atonia index (RAI). Group RSWA metrics were comparatively analyzed. Receiver operating characteristic curves determined optimized area under the curve (AUC) and maximized specificity and sensitivity diagnostic iRBD RSWA thresholds., Results: All mean RSWA metrics were higher in patients with iRBD than in controls ( P < .05), except for selected anterior tibialis measures. Optimized, maximal specificity AUC diagnostic cutoffs for coprimary outcomes were: SM "any" 6.5%, 14.0% (AUC = 92.5%) and combined SM+FDS "any" 15.1%, 27.4% (AUC = 95.8%), while SM burst durations were 0.72, and 0.72 seconds (AUC 90.2%) and FDS RAI = 0.930, 0.888 (AUC 92.8%)., Conclusions: This study provides evidence for current quantitative RSWA diagnostic thresholds in chin and individual 4 limb muscles applicable in different iRBD clinical settings and confirms the key value of SM or SM+FDS to assure accurate iRBD diagnosis. Evolving iRBD recognition underscores the necessity of continuous assessment with future large, prospective, well-harmonized, multicenter polysomnographic analyses., Citation: Leclair-Visonneau L, Feemster JC, Bibi N, et al. Contemporary diagnostic visual and automated polysomnographic REM sleep without atonia thresholds in isolated REM sleep behavior disorder. J Clin Sleep Med . 2024;20(2):279-291., (© 2024 American Academy of Sleep Medicine.)

Study Objectives: The body-first Parkinson's disease (PD) hypothesis suggests initial gut Lewy body pathology that propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels. This disease course may also be the most likely in PD with rapid eye movement sleep behavior disorder (RBD)., Objectives: We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by non-rapid eye movement (NREM) sleep and wakefulness polysomnographic markers., Methods: In a study involving 43 patients with PD who underwent clinical examination, rectosigmoidoscopy, and polysomnography, we detected PASH on colonic biopsies using whole-mount immunostaining. We performed a visual semi-quantitative and automated quantification of spindle and slow wave features of NREM sleep, and the wake dominant frequency, and then determined Braak and Arizona stage classifications for PD severity based on sleep and wake electroencephalographic features., Results: The visual analysis aligned with the automated quantified spindle characteristics and the wake dominant frequency. Altered NREM sleep and wake parameters correlated with markers of PD severity, colonic PASH, and RBD diagnosis. Colonic PASH frequency also increased in parallel to presumed PD Braak and Arizona stage classifications., Conclusions: Colonic PASH in PD is strongly associated with widespread brain sleep and wake dysfunction, pointing toward likely extensive diffusion of the pathological process in the presumptive body-first PD phenotype. Visual and automated analyses of polysomnography signals provide useful markers to gauge covert brain dysfunction in PD., Statement of Significance: The presence of gut synucleinopathy in Parkinson's disease can be linked to the body-first hypothesis in its pathophysiology. This study, performed in a cohort of 43 patients with Parkinson's disease that underwent clinical assessment, rectosigmoidoscopy and polysomnography, provides evidence that colonic neuropathology in Parkinson's disease is associated with widespread brain dysfunction, as evaluated by wake and non-rapid eye movement sleep polysomnographic markers. Our results support the assumption of an extensive diffusion of the pathological process to diencephalic and neocortical structures in the presumptive body-first phenotype. They also suggest the use of routine polysomnography in phenotyping patients with Parkinson's disease. Future studies should investigate the brain diffusion pattern and its sleep markers in the hypothesized brain-first phenotype of Parkinson's disease.

The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson's disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson's disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson's disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We recently demonstrated in a randomized controlled trial (APOMORPHEE, NCT02940912) that night-time only subcutaneous apomorphine infusion improves sleep disturbances and insomnia in patients with advanced Parkinson's disease and moderate to severe insomnia., Objectives: To identify the best candidates for receiving night-time only subcutaneous apomorphine infusion in routine care., Methods: In this post-hoc analysis of APOMORPHEE, we compared the characteristics of patients according to whether they chose to continue night-time only subcutaneous apomorphine infusion at the end of the study period or not., Results: Half of the patients (22/42) chose to continue the treatment. Off duration (day or night), painful Off dystonia, and insomnia severity at baseline were associated with night-time only apomorphine continuation. Multivariate analysis retained only Off duration as an independent predictor of continuation., Conclusions: The best candidates for night-time only apomorphine are patients with severe and prolonged Off periods (day or night) and severe insomnia., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Purpose: Early prognostication of neurologic outcome in neonates and children supported with extra-corporeal membrane oxygenation (ECMO) is challenging. Amplitude-integrated EEG (aEEG) offers the advantages of continuous monitoring and 24-hours availability at the bedside for intensive care unit providers. The objective of this study was to describe the early electrophysiological background patterns of neonates and children undergoing ECMO and their association with neurologic outcomes., Methods: This was a retrospective review of neonates and children undergoing ECMO and monitored with aEEG. Amplitude-integrated EEG was summarized as an aEEG background score determined within the first 24 hours of ECMO and divided in 3-hour periods. Screening for electrical seizures was performed throughout the full ECMO duration. Neurologic outcome was defined by the Pediatric Cerebral Performance Category score at hospital discharge., Results: Seventy-three patients (median age 79 days [8-660], median weight 4.78 kg [3.24-10.02]) were included in the analysis. Thirty-two patients had a favorable neurologic outcome and 41 had an unfavorable neurologic outcome group at hospital discharge. A 24-hour aEEG background score >17 was associated with an unfavorable outcome with a sensitivity of 44%, a specificity of 97%, a positive predictive value of 95%, and a negative predictive value of 57%. In multivariate analysis, 24-hour aEEG background score was associated with unfavorable outcome (hazard ratio, 6.1; p = 0.001; 95% confidence interval, 2.31-16.24). The presence of seizures was not associated with neurologic outcome at hospital discharge., Conclusions: Continuous aEEG provides accurate neurologic prognostication in neonates and children supported with ECMO. Early aEEG monitoring may help intensive care unit providers to guide clinical care and family counseling., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Study Objectives: Isolated REM sleep behavior disorder (iRBD) carries a high lifetime risk for phenoconversion to a defined neurodegenerative disease (NDD) including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. We aimed to examine iRBD patient values and preferences regarding prognostic counseling., Methods: One hundred thirteen iRBD patient participants enrolled in the Mayo Clinic iRBD Patient Registry were sent an email survey concerning their values and preferences concerning NDD prognostic counseling and their experiences following diagnosis with iRBD., Results: Of 81 respondents (71.7% response rate), the majority were men (74.0%) with an average age of 65.7 (±9.7) years. Responses indicated a strong preference toward receiving prognostic information about possible future NDD development. 92.5% of respondents felt knowledge concerning personal NDD risk was important, while 87.6% indicated prognostic discussions were important to maintaining trust in their physician. 95.7% indicated a desire for more information, while only 4.3% desired less information regarding their NDD prognostic risk. Most respondents strongly agreed that prognostic information was important to discuss with their family and friends and inform future life planning, and most expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia., Conclusions: Most iRBD patients indicated strong preferences for disclosure of NDD prognostic risk and indicated that prognostic information was important for family discussions and future life planning. Future broader surveys and qualitative studies of clinic-based and ultimately community dwelling iRBD patients' values and preferences are needed to guide appropriately tailored and individualized prognostic counseling approaches following iRBD diagnosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale: Randomized controlled trials showed no effect of positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA) on cardiovascular (CV) risk. However, patient selection and low PAP adherence preclude the generalization of their data to clinical samples. Objectives: To evaluate the association between hours of PAP use, mortality, and CV morbidity in real-life conditions. Methods: Data from the Pays de la Loire Cohort were linked to health administrative data to identify incident major adverse cardiovascular events (MACEs; a composite outcome of mortality, stroke, and cardiac diseases) in patients with OSA who were prescribed PAP. Cox proportional hazards analyses were conducted to evaluate the association between MACEs and quartiles of average daily PAP use over the study period. Measurements and Main Results: After a median follow-up of 6.6 years, 961 of 5,138 patients experienced MACEs. Considering nonadherent patients (0-4 h/night) as the reference group, adjusted hazard ratios (95% confidence intervals) for MACEs were 0.87 (0.73-1.04) for the 4-6 h/night group, 0.75 (0.62-0.92) for the 6-7 h/night group, and 0.78 (0.65-0.93) for the ⩾7 h/night group ( P  = 0.0130). Sensitivity analyses using causal inference approaches confirmed the association of PAP use with MACEs. The association was stronger in male patients ( P value for interaction = 0.0004), patients without overt CV disease at diagnosis ( P  < 0.0001), and those belonging to the excessively sleepy symptom subtype ( P  = 0.060). Conclusions: These real-life clinical data demonstrate a dose-response relationship between PAP adherence and incident MACEs in OSA. Patient support programs may help improve PAP adherence and CV outcomes in patients with OSA.

Alpha-synuclein deposits, the pathological hallmarks of Parkinson's disease, are consistently found in the gastrointestinal tract of parkinsonian subjects. These observations have raised the potential that endoscopically obtainable mucosal biopsies can aid to a molecular diagnosis of the disease. The possible usefulness of mucosal biopsies is, however, not limited to the detection of alpha-synuclein, but also extends to other essential aspects underlying pathophysiological mechanisms of gastrointestinal manifestations in Parkinson's disease. The aim of the current review is to provide an appraisal of the existing studies showing that gastrointestinal biopsies can be used for the analysis of enteric neuronal and glial cell morphology, intestinal epithelial barrier function, and gastrointestinal inflammation in Parkinson's disease. A perspective on the generation of organoids with GI biopsies and the potential use of single-cell and spatial transcriptomic technologies will be also addressed., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: It is now well established that phosphorylated alpha-synuclein histopathology, the pathologic hallmark of Parkinson's disease (PD) is not limited to the brain but also extends to the enteric nervous system (ENS). This observation led to the hypothesis that the ENS could play a pivotal role in the development of PD. Research on the enteric synucleinopathy has, however, been hampered by difficulties in detecting phosphorylated alpha-synuclein in the ENS by Western blotting, even when the transferred membrane is fixed with an optimized protocol. This suggests that the available antibodies used in previous studies lacked of sensitivity for the detection of phosphorylated alpha-synuclein at Ser129 in enteric neurons. Here, we evaluated three recent commercially available phospho-alpha-synuclein antibodies and compared them to two antibodies used in previous research., Methods: The specificity and sensitivity of the 5 antibodies were evaluated by Western blot performed with recombinant alpha-synuclein and with protein lysates from rat primary cultures of ENS. In primary culture of ENS, additional experiments were performed with the most specific antibody in order to modulate alpha-synuclein phosphorylation and to validate its utilization in immunofluorescence experiments., Results: The rabbit monoclonal antibody D1R1R uniquely and robustly detected endogenous phosphorylated alpha-synuclein at Ser129 in rat primary culture of ENS without any non-specific bands, allowing for a reliable analysis of phosphorylated alpha-synuclein regulation by pharmacologic means., Conclusions and Inferences: Using D1R1R antibody together with the optimized protocol for membrane fixation may help deciphering the signaling pathways involved in enteric alpha-synuclein post-translational regulation in PD., (© 2022 John Wiley & Sons Ltd.)

Background: Insomnia is a frequent complaint of patients with Parkinson's disease, and it negatively affects quality of life. Drugs that improve both sleep and parkinsonism would be of major benefit to patients with Parkinson's disease-related insomnia. We aimed to test the safety and efficacy of subcutaneous night-time only apomorphine infusion in patients with Parkinson's disease and insomnia., Methods: We did a randomised, multicentre, double-blind, placebo-controlled, crossover trial in 11 expert centres in Parkinson's disease and sleep centres in France. Participants aged 35-90 years with fluctuating Parkinson's disease and moderate to severe insomnia (Insomnia Severity Index score ≥15) were randomly assigned to either first receive night-time subcutaneous apomorphine (up to 5 mg/h) or matching placebo. Randomisation was done using a computer-generated plan in blocks of four, stratified by centre. This first intervention was followed by a 14-night washout period, then crossover to the other intervention. The treatment periods consisted of a 10-night titration phase followed by a 7-night fixed-dose phase. The dose was adjusted during the titration phase on the basis of a daily telephone call assessing sleep quality and treatment tolerability. The primary efficacy endpoint was the difference in Parkinson's disease sleep scale (PDSS) scores from the beginning to the end of each treatment period. Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT02940912., Findings: Between Jan 31, 2017, and Jan 29, 2021, 46 participants were enrolled. 25 (54%) patients were randomly assigned to receive apomorphine first and 21 (46%) patients to receive placebo first. Mean change in PDSS score was significantly greater with night-time apomorphine infusion (15·18 [SD 24·34]) compared with placebo (5·23 [21·52]; treatment effect 9·95 [95% CI 0·88-19·03]; p=0·041). Adverse events were reported in 25 (54%) participants during the apomorphine period and in 17 (37%) participants during the placebo period (p=0·16). Apomorphine was associated with more frequent dizziness than was placebo (seven [15%] vs 0; p=0·041)., Interpretation: Subcutaneous night-time only apomorphine infusion improved sleep disturbances according to difference on PDSS score, with an overall safety profile consistent with previous studies in Parkinson's disease. This treatment might be useful to manage sleep disturbances in patients with advanced Parkinson's disease and moderate to severe insomnia., Funding: Orkyn and Aguettant Pharma., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests SLS has received travel grants from UCB Pharma. VCDC has served on a scientific advisory board for Jazz Pharma and received honoraria for speeches from Orkyn, Aguettant and LVL medical; received research support from Orkyn and Aguettant; and received travel grants from Orkyn and Aguettant. IA has received consultancy fees from IDORSIA Pharma, ONO Pharma, and Roche Pharma, and payment for a lecture by UCB Pharma. ER has served on scientific advisory boards for Orkyn, Aguettant, Merz-Pharma, and Allergan; received honoraria for speeches from Orkyn, Aguettant, Merz-Pharma, Everpharma, Elivie, and the International Parkinson and Movement Disorders Society; received research support from Merz-Pharma, Orkyn, Aguettant, Elivie, Ipsen, Allergan, Everpharma, Fondation Desmarest, AMADYS, Fonds de Dotation Brou de Laurière, ADCY5.org, Agence Nationale de la Recherche, and Societé Française de Médecine Esthétique; received travel grants from Vitalaire, PEPS development, Aguettant, Merz-Pharma, Ipsen, Merck, Orkyn, Elivie, Adelia Medical, Dystonia Medical Research Foundation, International Parkinson and Movement Disorders Society, European Academy of Neurology, and the International Association of Parkinsonism and Related Disorders. MA declares honoraria and travel grants from AbbVie, Teva, Merz, Orkyn, Aguettant, Actelion Pharmaceuticals, and Johnson and Johnson. PD has received support from UCB Pharma for attending a meeting, and speaker's honoraria from Roche. CA has received travel grants from Merz, and honoraria for presentations from Abbvie and Orkyn. LLV has received travel grants from UCB Pharma and Bioprojet. SD has received support for attending meetings from Aguettant, Orkyn, LVL, Homeperf, Elivie, and Boston Scientific; honoraria for presentations from Aguettant, Orkyn, LVL, Medtronic, Homeperf, Elivie, and Boston Scientific; and consulting fees from Aguettant, Orkyn, and Boston Scientific. DD has received consultancy fees for a scientific advisory board for Abbvie, Alterity, Orkyn, Air Liquide, Apopharma, Lundbeck, Everpharma, Boston Scientific, and the Cure Parkinson Trust; grants from the French Ministry of Health: projet hospitalier de recherche clinique grants; French Ministry of Research: ANR; European Preclinical Research: Coen; European Clinical Research: Horizon 2020, charities from France Parkinson, ARSLA Foundation; Foundations: University of Lille, CA; and has equity stake from InBrain Pharma; InVenis biotherapies. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Increasing evidence suggests that obstructive sleep apnoea (OSA) contributes to cancer risk; however, limited data are available on the impact of continuous positive airway pressure (CPAP) therapy on cancer incidence. We aimed to determine whether adherence to CPAP therapy is associated with a reduction in all-cancer incidence compared with nonadherent patients with OSA., Methods: The study relied on data collected by the multicentre Pays de la Loire Sleep Cohort study, linked to health administrative data, so as to identify new-onset cancer. We included patients who were prescribed CPAP for OSA, with no history of cancer before the diagnostic sleep study or during the first year of CPAP. Patients with documented CPAP use for ≥4 h per night were defined as adherent. Those who discontinued or used CPAP <4 h per night constituted the nonadherent group. A propensity score inverse probability of treatment weighting analysis was performed to assess the effect of CPAP adherence on cancer risk., Results: After a median (interquartile range) follow-up of 5.4 (3.1-8.0) years, 437 (9.7%) out of 4499 patients developed cancer: 194 (10.7%) in the nonadherent group (n=1817) and 243 (9.1%) in adherent patients (n=2682). The final weighted model showed no significant impact of CPAP adherence on all-cause cancer risk (subdistribution hazard ratio 0.94, 95% CI 0.78-1.14)., Conclusions: Adherence to CPAP therapy in OSA patients was not associated with a reduction in all-cancer incidence. Whether adherent CPAP therapy of OSA might reduce the risk of specific cancer sites should be further evaluated., Competing Interests: Conflict of interest: G. Justeau has nothing to disclose. Conflict of interest: S. Bailly reports consulting fees for methodology and statistical analyses from Institut Recherche en Santé Respiratoire des Pays de la Loire, outside the submitted work. Conflict of interest: C. Gervès-Pinquié has nothing to disclose. Conflict of interest: W. Trzepizur has nothing to disclose. Conflict of interest: N. Meslier has nothing to disclose. Conflict of interest: F. Goupil has nothing to disclose. Conflict of interest: T. Pigeanne has nothing to disclose. Conflict of interest: S. Launois has nothing to disclose. Conflict of interest: L. Leclair-Visonneau has nothing to disclose. Conflict of interest: P. Masson has nothing to disclose. Conflict of interest: A. Bizieux-Thaminy has nothing to disclose. Conflict of interest: J-L. Racineux has nothing to disclose. Conflict of interest: D. Gozal reports NIH grants, outside the submitted work. Conflict of interest: F. Gagnadoux reports support for the present manuscript from Institut Recherche en Santé Respiratoire des Pays de la Loire to the University Hospital of Angers; consulting fees from Nyxoah, Sefam and ResMed; payment or honoraria for lectures from Cidelec, Asten Santé and Boehringer Ingelheim; payment for expert testimony from Boehringer Ingelheim; support for attending meetings and/or travel from Asten Santé and Actelion; participation on a data safety monitoring board or advisory board for Jazz Pharmaceutical; receipt of equipment, materials, drugs, medical writing, gifts or other services from Inspire to the University Hospital of Angers, outside the present work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Objective: Adherence is a critical issue in the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP). Approximately 40% of patients treated with CPAP are at risk of discontinuation or insufficient use (< 4 h/night). Assuming that the first few days on CPAP are critical for continued treatment, we tested the predictive value at day 14 (D14) of the Philips Adherence Profiler™ (AP) algorithm for adherence at 3 months (D90)., Method: The AP™ algorithm uses CPAP machine data hosted in the database of EncoreAnywhere™. This retrospective study involved 457 patients (66% men, 60.0 ± 11.9 years; BMI = 31.2 ± 5.9 kg/m 2 ; AHI = 37.8 ± 19.2; Epworth score = 10.0 ± 4.8) from the Pays de la Loire Sleep Cohort. At D90, 88% of the patients were adherent as defined by a mean daily CPAP use of ≥ 4 h., Results: In a univariate analysis, the factors significantly associated with CPAP adherence at D90 were older age, lower BMI, CPAP adherence (≥ 4 h/night) at D14, and AP™ prediction at D14. In a multivariate analysis, only older age (OR 2.10 [1.29-3.41], p = 0.003) and the AP™ prediction at D14 (OR 16.99 [7.26-39.75], p < 0.0001) were significant predictors. CPAP adherence at D90 was not associated with device-derived residual events, nor with the levels of pressure or leakage except in the case of very significant leakage when it persisted for 90 days., Conclusion: Automatic telemonitoring algorithms are relevant tools for early prediction of CPAP therapy adherence and may make it possible to focus therapeutic follow-up efforts on patients who are at risk of non-adherence.

Background: Previous studies have yielded inconsistent findings regarding the association between OSA and cancer in humans., Research Question: Is there an association between indexes of sleep-disordered breathing severity and cancer incidence in patients investigated for suspected OSA?, Study Design and Methods: Data from a large multicenter cohort of cancer-free patients investigated for OSA were linked to health administrative data to identify new-onset cancer. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the association of cancer incidence with OSA severity and nocturnal hypoxemia., Results: After a median follow-up period of 5.8 years (interquartile range, 3.8-7.8), 718 of 8,748 patients (8.2%) had received a diagnosis of cancer. On unadjusted Kaplan-Meier survival analyses, cancer incidence was associated with increasing severity of OSA (log-rank test, P < .0005) and nocturnal hypoxemia (log-rank test, P < .0001 for both oxygen desaturation index and percent night time with oxygen saturation < 90% [T90]). After adjustment for anthropomorphic data, smoking and alcohol consumption, comorbid cardiac, metabolic, and respiratory diseases, marital status, type of sleep study, and study site, only T90 was associated with cancer incidence (adjusted hazard ratio, 1.33; 95% CI, 1.05-1.68 for T90 ≥ 13% vs < 0.01%; P = .02). On stratified analyses, the association between T90 and cancer appeared stronger in older patients with obesity and no adequate OSA therapy. Among the most frequent cancer sites, nocturnal hypoxemia was associated with lung and breast malignancies., Interpretation: Nocturnal hypoxemia was associated with all-cancer incidence in patients investigated for OSA. Whether OSA therapy might reduce the risk of cancer needs further evaluation., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

An accumulating body of literature has emerged in the past 25 years to show that Parkinson's disease (PD) is not only a disorder of the brain but also of the gastrointestinal tract and more generally of the gut-brain axis. Gastrointestinal symptoms occur in almost every PD patient at some point and in nearly every case examined pathologically autopsy studies find alpha-synuclein deposits, the pathological hallmarks of PD, in the enteric nervous system. This concept of 'enteric synucleinopathy' led to the hypothesis that the enteric nervous system might play a pivotal role in the initiation and spreading of PD. Although this hypothesis opens up interesting perspectives on the pathogenesis of neurodegenerative disorders, some important questions are still pending. The present opinion paper describes and compares the physiological and pathophysiological properties of alpha-synuclein in the brain and the enteric nervous system. We conclude that the existing data supports the existence of pathological alpha-synuclein species in the gut in PD. We also discuss if gut-brain interactions are important in other neurodegenerative disorders.

While the pathogenesis of Parkinson's disease is not fully understood, there is increasing evidence that inflammatory responses in the brain are implicated in both disease initiation and progression. The inflammatory process in Parkinson's disease is, however, not limited to the brain but also involves the gastrointestinal tract. High amounts of cytokines and inflammatory markers are found in the colon of Parkinson's disease patients and there is now strong epidemiological and genetical evidence linking Parkinson's disease to inflammatory bowel diseases. Recent findings obtained in both experimental inflammatory bowel diseases and Parkinson's disease further support a bidirectional link between gastrointestinal inflammation and brain neurodegeneration. Altogether, these observations suggest a role for gastrointestinal inflammation in the initiation and progression of Parkinson's disease.

Purposes: Amplitude-integrated EEG (aEEG) has been widely developed in neonatal intensive care unit, but few studies focused on pediatric intensive care unit. Furthermore, reliability of aEEG under real-life conditions is unknown., Methods: Participants were nurses from a 12-bed pediatric intensive care unit in a referral university hospital in France. Amplitude EEG was implemented after standardized training, including e-learning course, individual feedback and bedside teaching concerning monitoring installation, background classification patterns recognition, artefact analysis, and seizure detection. The primary judgment criterion was the agreement (Cohen Kappa) between nurses and aEEG experts for the detection of abnormal aEEG traces (moderately or severely altered background pattern according to Hellström-Westas classification and/or seizure activity)., Results: During the study period, 196 consecutives traces from 79 patients were analyzed by 51 nurses. According to expert's classification, 53% of traces were abnormal, including 17.5% of severely abnormal traces (severely altered traces and/or seizure activity) and 14% exhibiting seizure activity. Moderate agreement between experts and nurses was found for detection of any abnormal trace (k = 0.53; 95% confidence interval [CI]: 0.39-0.67). Substantial agreement was found for severely altered traces (k = 0.71; 95% CI: 0.57-0.85). Finally, fair agreement was found for seizure detection (irrespective of background classification, k = 0.40; 95% CI: 0.25-0.54)., Conclusions: These results suggest that aEEG monitoring may be implemented in routine nursing care in pediatric intensive care unit. Further training courses are needed to enhance nurses' skill in detecting seizures activity at the bedside.

Objectives: To assess the ability of amplitude-integrated electroencephalography monitoring within 24 hours of the return of spontaneous circulation to prognosticate neurologic outcomes in children following cardiac arrest DESIGN:: Retrospective review of prospectively recorded data. An amplitude-integrated electroencephalography background score was calculated according to background activity during the first 24 hours after return of spontaneous circulation, a higher score correlating with more impaired background activity. The primary endpoint was the neurologic outcome as defined by the Pediatric Cerebral Performance Category at PICU discharge (Pediatric Cerebral Performance Category 1-3: a good neurologic outcome; Pediatric Cerebral Performance Category 4-6: a poor neurologic outcome)., Setting: A referral PICU., Patients: Thirty children with a median age of 10 months (2-38 mo) and a male/female sex ratio of 1.3 were included., Interventions: None., Measurements and Main Results: Eighteen patients were assigned to the favorable outcome group and 12 to the unfavorable outcome group. The median time between return of spontaneous circulation and amplitude-integrated electroencephalography initiation was 4 hours (3-9 hr). The amplitude-integrated electroencephalography score within 24 hours after return of spontaneous circulation was significantly higher in the children with poor outcomes compared with those with good outcomes (12 ± 4 vs 25 ± 8; p < 0.001). Background activity during amplitude-integrated electroencephalography monitoring was able to predict poor neurologic outcomes at PICU discharge, with an area under the receiver operating characteristic curve of 0.91 (95% CI, 0.81-1.00)., Conclusions: Early amplitude-integrated electroencephalography monitoring may help predict poor neurologic outcomes in children within 24 hours following cardiac arrest.