EEG Spectro-Spatial Covariance Patterns Related to Phenoconversion in Isolated REM Sleep Behavior Disorder and Their Longitudinal Trajectories in α-Synucleinopathies.

STUDY OBJECTIVES: This study aimed to identify electroencephalographic (EEG) spectro-spatial covariance patterns associated with phenoconversion in isolated rapid eye movement sleep behavior disorder (iRBD) patients and explore their longitudinal trajectories within α-synucleinopathies. METHODS: We assessed 47 participants, including 35 iRBD patients and 12 healthy controls (HC), through baseline eye-closed resting EEGs. iRBD patients underwent follow-up EEG assessments and 18 iRBD patients converted (12 to Parkinson's disease (PD), 6 to dementia with Lewy bodies (DLB)) during follow-up. We derived EEG spectro-spatial covariance patterns for PD-RBD and DLB-RBD from converters and HC. Correlations with motor and cognitive function, baseline distinctions among iRBD converters and nonconverters, and longitudinal trajectories were examined. RESULTS: At baseline, converters exhibited higher PD-RBD and DLB-RBD beta2 pattern scores compared to nonconverters (each area under curve (AUC) = 0.7751). The delta and alpha spatial patterns effectively distinguished both PD and DLB converters from HC, with the alpha pattern showing high discriminative power (AUC = 0.9097 for PD-RBD, 0.9306 for DLB-RBD). Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III scores correlated positively with PD-RBD and DLB-RBD delta patterns (Spearman's rho = 0.688, p = 0.00014; rho = 0.539, p = 0.0055, respectively), with age and sex as cofactors. Distinct trajectories emerged during follow-up among PD converters, DLB converters, and iRBD nonconverters. CONCLUSIONS: Unique EEG spectro-spatial patterns specific to PD-RBD and DLB-RBD offer potential as predictive markers for phenoconversion to α-synucleinopathies in iRBD.

Risk of encephalitis and meningitis after COVID-19 vaccination in South Korea: a self-controlled case series analysis.

BACKGROUND: Several neurological manifestations shortly after a receipt of coronavirus infectious disease 2019 (COVID-19) vaccine have been described in the recent case reports. Among those, we sought to evaluate the risk of encephalitis and meningitis after COVID-19 vaccination in the entire South Korean population. METHODS: We conducted self-controlled case series (SCCS) analysis using the COVID-19 immunization record data from the Korea Disease Control Agency between February 2021 and March 2022, linked with the National Health Insurance Database between January 2021 and October 2022. We retrieved all medical claims of adults aged 18 years or older who received at least one dose of COVID-19 vaccines (BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S), and included only those who had a diagnosis record for encephalitis or meningitis within the 240-day post-vaccination period. With day 0 defined as the date of vaccination, risk window was defined as days 1-28 and the control window as the remainder period excluding the risk windows within the 240-day period. We used conditional Poisson regression to estimate the incidence rate ratios (IRR) with 95% confidence intervals (CI), stratified by dose and vaccine type. RESULTS: From 129,956,027 COVID-19 vaccine doses administered to 44,564,345 individuals, there were 251 and 398 cases of encephalitis and meningitis during the risk window, corresponding to 1.9 and 3.1 cases per 1 million doses, respectively. Overall, there was an increased risk of encephalitis in the first 28 days of COVID-19 vaccination (IRR 1.26; 95% CI 1.08-1.47), which was only significant after a receipt of ChAdOx1-S (1.49; 1.03-2.15). For meningitis, no increased risk was observed after any dose of COVID-19 vaccine (IRR 1.03; 95% CI 0.91-1.16). CONCLUSIONS: Our findings suggest an overall increased risk of encephalitis after COVID-19 vaccination. However, the absolute risk was small and should not impede COVID-19 vaccine confidence. No significant association was found between the risk of meningitis and COVID-19 vaccination.

EEG-based machine learning models for the prediction of phenoconversion time and subtype in isolated rapid eye movement sleep behavior disorder.

STUDY OBJECTIVES: Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathies and eventually phenoconverts to overt neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Associations of baseline resting-state electroencephalography (EEG) with phenoconversion have been reported. In this study, we aimed to develop machine learning models to predict phenoconversion time and subtype using baseline EEG features in patients with iRBD. METHODS: At baseline, resting-state EEG and neurological assessments were performed on patients with iRBD. Calculated EEG features included spectral power, weighted phase lag index, and Shannon entropy. Three models were used for survival prediction, and four models were used for α-synucleinopathy subtype prediction. The models were externally validated using data from a different institution. RESULTS: A total of 236 iRBD patients were followed up for up to 8 years (mean 3.5 years), and 31 patients converted to α-synucleinopathies (16 PD, 9 DLB, 6 MSA). The best model for survival prediction was the random survival forest model with an integrated Brier score of 0.114 and a concordance index of 0.775. The K-nearest neighbor model was the best model for subtype prediction with an area under the receiver operating characteristic curve of 0.901. Slowing of the EEG was an important feature for both models. CONCLUSIONS: Machine learning models using baseline EEG features can be used to predict phenoconversion time and its subtype in patients with iRBD. Further research including large sample data from many countries is needed to make a more robust model.

Quantitative Network Comparisons of REM Sleep Without Atonia Across the α-Synucleinopathy Spectrum: A Systematic Review.

Purpose: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by REM sleep without atonia (RWA) and is regarded as the prodromal stage of α-synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). RWA is also associated with neurodegeneration driven by α-synucleinopathy. However, the level of RWA across the α-synucleinopathy spectrum remains elusive. We aimed to rate the percentage of RWA across the α-synucleinopathy spectrum, encompassing prodromal and overt phenotypes. Methods: A systematic search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases. We included cohort, cross-sectional, and case-control studies comparing the RWA percentage during REM sleep evaluated by tonic chin activity (RWA%-T) or by phasic chin activity (RWA%-P) across the α-synucleinopathy spectrum. Bayesian network meta-analysis was used to combine both direct and indirect evidence regarding the group differences in the RWA%-T and RWA%-P. The surface under the cumulative ranking curve was used to estimate the ranked probability. Results: Fifteen articles met the inclusion criteria. The investigations included 204 iRBD, 295 PD with RBD (PDwtRBD), 187 PD without RBD (PDwoRBD), 42 MSAwtRBD, 9 DLBwtRBD patients, and 246 controls. MSAwtRBD ranked first in RWA%-T, whereas iRBD ranked first in RWA%-P. RWA% in PDwoRBD patients was comparable to that in the controls and was lower than that in PDwtRBD patients. Conclusion: Overt phenotypes such as MSAwtRBD and PDwtRBD ranked high in RWA%-T, whereas iRBD, a prodromal type, ranked highest in RWA%-P. Taken together, our data suggest that the percentage of neurodegeneration in RBD patients may be associated with RWA%-T rather than RWA%-P. Prospero Registration Number: CRD42021276445.

Management of convulsive status epilepticus: recent updates.

Convulsive status epilepticus (SE) is a medical emergency associated with high morbidity and mortality. Recently, clinical trials and meta-analyses investigating medical treatment of SE have been published. Benzodiazepine is well known as the first-line treatment for SE. Recent evidence suggests the equivalence of intravenous fosphenytoin, valproate, and levetiracetam for treatment of established SE. There is lack of evidence regarding treatment for refractory SE. Intravenous midazolam is commonly used, and recent evidence supports the use of ketamine. Additional studies are needed to improve the management of convulsive SE.

Quantitative measurement of motor activity during sleep in isolated REM sleep behavior disorder patients using actigraphy before and after treatment with clonazepam.

STUDY OBJECTIVES: We conducted a prospective study to quantify motor activity during sleep measured by actigraphy before and after 3 months of treatment with clonazepam in patients with video-polysomnography (vPSG) confirmed isolated rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: The motor activity amount (MAA) and the motor activity block (MAB) during sleep were obtained from actigraphy. Then, we compared quantitative actigraphic measures with the results of the REM sleep behavior disorder questionnaire for the previous 3-month period (RBDQ-3M) and of the Clinical Global Impression-Improvement scale (CGI-I), and analyzed correlations between baseline vPSG measures and actigraphic measures. RESULTS: Twenty-three iRBD patients were included in the study. After medication treatment, large activity MAA dropped in 39% of patients, and the number of MABs decreased in 30% of patients when applying 50% reduction criteria. 52% of patients showed more than 50% improvement in either one. On the other hand, 43% of patients answered "much or very much improved" on the CGI-I, and RBDQ-3M was reduced by more than half in 35% of patients. However, there was no significant association between the subjective and objective measures. Phasic submental muscle activity during REM sleep was highly correlated with small activity MAA (Spearman's rho = 0.78, p < .001) while proximal and axial movements during REM sleep correlated with large activity MAA (rho = 0.47, p = .030 for proximal movements, rho = 0.47, p = .032 for axial movements). CONCLUSIONS: Our findings imply that quantifying motor activity during sleep using actigraphy can objectively assess therapeutic response in drug trials in patients with iRBD.

Altered functional connectivity of the ascending reticular activating system in obstructive sleep apnea.

Repeated arousals during sleep in obstructive sleep apnea (OSA) may lead to altered functional connectivity (FC) of the ascending reticular activating system (ARAS). We evaluated resting-state FC between eight ARAS nuclei and 105 cortical/subcortical regions in OSA patients and healthy controls. Fifty patients with moderate to severe OSA and 20 controls underwent overnight polysomnography and resting-state functional magnetic resonance imaging. Seed-to-voxel analysis of ARAS-cortex FC was compared between OSA patients and controls. The ARAS nuclei included the locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), and ventral tegmental area (VTA). FC values of three ARAS nuclei (the LC, LDTg, and VTA) significantly differed between the groups. FC of the LC with the precuneus, posterior cingulate gyrus, and right lateral occipital cortex (LOC) was stronger in OSA patients than controls. FC between the LDTg and right LOC was stronger in OSA patients than controls, but FC between the VTA and right LOC was weaker. Average LC-cortex FC values positively correlated with the arousal, apnea, and apnea-hypopnea index in OSA patients. Alterations in ARAS-cortex FC were observed in OSA patients. The strength of LC-cortex noradrenergic FC was related to arousal or OSA severity in patients.

Change of iron content in brain regions after intravenous iron therapy in restless legs syndrome: quantitative susceptibility mapping study.

STUDY OBJECTIVES: The pathomechanism of restless legs syndrome (RLS) is related to brain iron deficiency and iron therapy is effective for RLS; however, the effect of iron therapy on human brain iron state has never been studied with magnetic resonance imaging. This study aimed to investigate the change of brain iron concentrations in patients with RLS after intravenous iron therapy using quantitative susceptibility mapping (QSM). METHODS: We enrolled 31 RLS patients and 20 healthy controls. All participants underwent initial baseline (t0) assessment using brain magnetic resonance imaging, serum iron status, and sleep questionnaires including international RLS Study Group rating scale (IRLS). RLS patients underwent follow-up tests at 6 and 24 weeks (t1 and t2) after receiving 1000 mg ferric carboxymaltose. Iron content of region-of-interest on QSM images was measured for 13 neural substrates using the fixed-shaped method. RESULTS: RLS symptoms evaluated using IRLS were significantly improved after iron treatment (t0: 29.7 ± 6.5, t1: 19.5 ± 8.5, t2: 21.3 ± 10.1; p < .001). There was no significant difference in susceptibility values between the controls and RLS patients at t0. In the caudate nucleus, putamen, and pulvinar thalamus of RLS patients, the QSM values differed significantly for three timepoints (p = .035, .048, and .032, respectively). The post-hoc analysis revealed that the QSM values increased at t1 in the caudate nucleus (66.8 ± 18.0 vs 76.4 ± 16.6, p = .037) and decreased from t1 to t2 in the putamen (69.4 ± 16.3 vs 62.5 ± 13.6, p = .025). Changes in the QSM values for the pulvinar and caudate nuclei at t1 were positively and negatively correlated with symptomatic improvement, respectively (r = 0.361 and -0.466, respectively). CONCLUSIONS: Intravenous iron treatment results in changes in brain iron content which correlate to reductions in RLS severity. This suggests a connection between symptom improvement and the associated specific brain regions constituting the sensorimotor network.

Spatiotemporal characteristics of cortical activities of REM sleep behavior disorder revealed by explainable machine learning using 3D convolutional neural network.

Isolated rapid eye movement sleep behavior disorder (iRBD) is a sleep disorder characterized by dream enactment behavior without any neurological disease and is frequently accompanied by cognitive dysfunction. The purpose of this study was to reveal the spatiotemporal characteristics of abnormal cortical activities underlying cognitive dysfunction in patients with iRBD based on an explainable machine learning approach. A convolutional neural network (CNN) was trained to discriminate the cortical activities of patients with iRBD and normal controls based on three-dimensional input data representing spatiotemporal cortical activities during an attention task. The input nodes critical for classification were determined to reveal the spatiotemporal characteristics of the cortical activities that were most relevant to cognitive impairment in iRBD. The trained classifiers showed high classification accuracy, while the identified critical input nodes were in line with preliminary knowledge of cortical dysfunction associated with iRBD in terms of both spatial location and temporal epoch for relevant cortical information processing for visuospatial attention tasks.

Performance of the Fitbit Charge 2 and Galaxy Watch 2 compared with polysomnography in assessing patients with obstructive sleep apnoea.

Wearable devices may be used to evaluate sleep in patients with obstructive sleep apnoea (OSA). This study compared the use of two wearable devices (the Fitbit Charge 2 (FC2) and Galaxy Watch 2 (GW2)) with that of polysomnography (PSG) for assessing the sleep time of OSA patients. A total of 127 consecutive patients with OSA underwent overnight PSG while wearing the FC2 and GW2 on their nondominant wrist. We compared the total sleep time (TST) determined by the devices with that obtained by PSG with paired t tests, Bland‒Altman plots, and interclass correlations. Moreover, we evaluated the time in each sleep stage and differences due to OSA severity. The mean age of the OSA patients was 50 years, and the mean apnoea-hypopnea index was 38.3 events/h. The recording failure rate was not significantly different between the GW2 and FC2 (15.7% vs. 8.7%, p = 0.106). Compared to PSG, both the FC2 and GW2 underestimated TST by 27.5 and 24.9 minutes, respectively. TST bias in both devices did not correlate with OSA severity. The FC2 and GW2 underestimated TST, which should be considered when monitoring sleep time in patients with OSA.

Altered intrinsic brain functional network dynamics in moderate-to-severe obstructive sleep apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) can affect temporal fluctuations in brain activity during rest. Dynamic functional connectivity (dFC) captures the fluctuations in FC during the resting state. This study aimed to investigate differences in dFC between moderate-to-severe OSA patients and healthy controls using resting-state functional magnetic resonance imaging (fMRI) and sliding-window analysis. METHODS: Thirty-seven consecutive patients with moderate-to-severe OSA and 16 age- and sex-matched controls underwent resting-state fMRI in the morning following overnight polysomnography. The dynamics of aberrant FC between the groups and the correlation between the dynamics and clinical variables were evaluated. RESULTS: dFC analysis revealed two distinct connectivity states: hypoconnected (State I) and hyperconnected (State II). In OSA patients, State I occurred 34% more often than in the controls and the occurrence of State II was proportionally reduced. The time in State I positively correlated with the Pittsburg Sleep Quality Index score in the OSA patients. CONCLUSIONS: This study showed dFC alterations in moderate-to-severe OSA patients, which may serve as a novel physiological biomarker for OSA.

Comparative efficacy of prolonged-release melatonin versus clonazepam for isolated rapid eye movement sleep behavior disorder.

PURPOSE: Clonazepam and melatonin are recommended as first-line treatments for isolated rapid eye movement (REM) sleep behavior disorder (iRBD). This study aimed to compare their efficacy and safety in REM sleep without atonia (RWA) and RBD-related symptoms. METHODS: This prospective, open-label, randomized trial included patients with video-polysomnography-confirmed iRBD. The patients were randomly assigned to receive either clonazepam 0.5 mg or prolonged-release (PR) melatonin 2 mg 30 min before bedtime for 4 weeks. The primary outcome was changes in RWA on follow-up polysomnography (PSG). Secondary endpoints were changes in other PSG parameters, clinical global improvement-impression scale (CGI-I) scores, and sleep questionnaire scores. The safety endpoint was adverse events. RESULTS: Of 40 patients with probable RBD considered, 34 were enrolled in the study and randomized. Visual scoring parameters of RWA indices were reduced, and automatic scoring parameters tended to be improved after clonazepam treatment but not after PR melatonin treatment. The proportion of N2 sleep was increased, and N3 and REM sleep were decreased only in the clonazepam group. The clonazepam group tended to answer "much or very much improvement" on the CGI-I more frequently than the PR melatonin group (p = 0.068). Daytime sleepiness and insomnia symptoms were reduced after PR melatonin but not after clonazepam. Depressive symptoms increased after clonazepam. Four of the patients (13.3%) reported mild to moderate adverse events, which were similar between the two groups. CONCLUSION: Four weeks of clonazepam, but not PR melatonin, improved RWA. RBD symptom improvement tended to be better after clonazepam than PR melatonin in exchange for increased depressive symptoms and daytime sleepiness. CLINICALTRIALS: gov identifier: NCT03255642 (first submitted August 21, 2017).

Deep learning signature of brain [18F]FDG PET associated with cognitive outcome of rapid eye movement sleep behavior disorder.

An objective biomarker to predict the outcome of isolated rapid eye movement sleep behavior disorder (iRBD) is crucial for the management. This study aimed to investigate cognitive signature of brain [18F]FDG PET based on deep learning (DL) for evaluating patients with iRBD. Fifty iRBD patients, 19 with mild cognitive impairment (MCI) (RBD-MCI) and 31 without MCI (RBD-nonMCI), were prospectively enrolled. A DL model for the cognitive signature was trained by using Alzheimer's Disease Neuroimaging Initiative database and transferred to baseline [18F]FDG PET from the iRBD cohort. The results showed that the DL-based cognitive dysfunction score was significantly higher in RBD-MCI than in RBD-nonMCI. The AUC of ROC curve for differentiating RBD-MCI from RBD-nonMCI was 0.70 (95% CI 0.56-0.82). The baseline DL-based cognitive dysfunction score was significantly higher in iRBD patients who showed a decrease in CERAD scores during 2 years than in those who did not. Brain metabolic features related to cognitive dysfunction-related regions of individual iRBD patients mainly included posterior cortical regions. This work demonstrates that the cognitive signature based on DL could be used to objectively evaluate cognitive function in iRBD. We suggest that this approach could be extended to an objective biomarker predicting cognitive decline and neurodegeneration in iRBD.

Emotional and Environmental Factors Aggravating Dream Enactment Behaviors in Patients with Isolated REM Sleep Behavior Disorder.

Objective: To identify emotional and environmental factors that aggravate dream enactment behaviors (DEBs) in isolated rapid eye movement (REM) sleep behavior disorder (iRBD). Methods: In this cross-sectional study, a total of 96 polysomnography-confirmed iRBD patients (mean age, 68.5 years; men, 68%) and their caregivers completed questionnaires regarding potential aggravating factors related to DEBs, including emotion/feelings (stress, anger, anxiety, depressive mood, fatigue, pain), food (alcohol, caffeine, overeating in the evening, fasting/hunger), activities and sleep patterns (strenuous exercise, sex before bed, conflict/fighting, sleep deprivation, oversleeping, sleeping away from home, watching TV before bed), weather/environmental factors (cloudy or rainy weather, heat, cold, noise) and medication (skipping medication, taking hypnotics). Results: The patients reported that stress (61%) was the most aggravating factor for DEBs, followed by anxiety (56%), anger (51%), fatigue (49%), and watching TV before bed (46%). Similarly, the caregivers reported that these factors were most relevant to the aggravation of DEBs in the patients, although some factors were ranked differently. In the subgroup analyses, aggravating factors for DEBs did not differ by RBD symptom severity. Interestingly, the proportion of patients experiencing DEB aggravation by stress, anxiety and depressive mood was significantly higher in women than in men. Furthermore, depressed patients reported that stress and cloudy or rainy weather made DEBs worse than nondepressed patients. Conclusion: Our results suggest that DEBs in iRBD patients may be mainly aggravated by emotional factors. These negative effects appeared to be more prominent in female and depressed patients.

Association of Nucleus Basalis of Meynert Functional Connectivity and Cognition in Idiopathic Rapid-Eye-Movement Sleep Behavior Disorder.

BACKGROUND AND PURPOSE: Cognitive impairments are common in isolated rapid-eye-movement sleep behavior disorder (iRBD), in which the cholinergic system may play an important role. This study aimed to characterize the cortical cholinergic activity using resting-state functional connectivity (FC) of the nucleus basalis of Meynert (NBM) according to the cognitive status of iRBD patients. METHODS: In this cross-sectional study, 33 patients with polysomnography-confirmed iRBD and 20 controls underwent neuropsychological evaluations and resting-state functional magnetic resonance imaging. Thirteen of the iRBD patients had mild cognitive impairment (iRBD-MCI), and the others were age-matched patients with normal cognition (iRBD-NC). The seed-to-voxel NBM-cortical FC was compared among the patients with iRBD-MCI, patients with iRBD-NC, and controls. Correlations between average values of significant clusters and cognitive function scores were calculated in the patients with iRBD. RESULTS: There were group differences in the FC of the NBM with the left lateral occipital cortex and lingual gyrus (adjusted for age, sex, and education level). The strength of FC was lower in the iRBD-MCI group than in the iRBD-NC and control groups (each post-hoc p<0.001). The average NBM-lateral occipital cortex FC was positively correlated with the memory-domain score in iRBD patients. CONCLUSIONS: The results obtained in this study support that cortical cholinergic activity is impaired in iRBD patients with MCI. FC between NBM and posterior regions may play a central role in the cognitive function of these patients.

White matter tract-specific microstructural disruption is associated with depressive symptoms in isolated RBD.

OBJECTIVE: White matter (WM) tract-specific changes may precede gray matter loss in isolated rapid eye movement sleep behavior disorder (iRBD). We aimed to evaluate tract-specific WM changes using tract-specific statistical analysis (TSSA) and their correlation with clinical variables in iRBD patients. METHODS: This was a cross-sectional single-center study of 50 polysomnography-confirmed iRBD patients and 20 age- and sex-matched controls. We used TSSA to identify tract-specific fractional anisotropy (FA) and mean diffusivity (MD) in fourteen major fiber tracts and analyzed between-group differences in these values. Correlations between FA or MD values and clinical variables, including RBD symptom severity, depression and cognition, were evaluated. RESULTS: Patients with iRBD showed lower FA in the right anterior thalamic radiation (ATR) and higher MD in the bilateral ATR and right inferior fronto-occipital fasciculus (IF-OF) than controls after adjusting for age, sex, and years of education. MD values in the IF-OF positively correlated with scores on the Korean version of the Rapid Eye Movement Sleep Behavior Disorder Questionnaire-Hong Kong (RBDQ-KR, p = 0.042) and the Korean version of the geriatric depression scale (GDS-K, p = 0.002) in iRBD patients. Only GDS-K scores independently correlated with IF-OF MD values after adjusting for RBDQ-KR scores (adjusted p = 0.026). CONCLUSION: This study suggests WM microstructural disruption in the bilateral ATR and right IF-OF in patients with iRBD and that alterations in the IF-OF may contribute to depressive symptoms.

Comparison of rapid eye movement without atonia quantification methods to diagnose rapid eye movement sleep behavior disorder: a systematic review.

STUDY OBJECTIVES: Rapid eye movement (REM) sleep without atonia (RWA) is essential for diagnosing REM sleep behavior disorder (RBD). Manual and automatic quantifications of RWA that use different criteria have been validated. This study compared the RWA quantification methods for diagnosing RBD. METHODS: The PubMed, EMBASE, Web of Science, and Cochrane Library databases were systemically searched for studies published from inception to December 2021. The inclusion criteria were cohort, cross-sectional, and case-control studies assessing the sensitivity and specificity of RWA quantification methods. Pooled estimates of the sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were determined. Risk of bias and certainty of evidence was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool and the Grading of Recommendations, Assessment, Development, and Evaluations framework, respectively. RESULTS: Fourteen articles including 402 patients with RBD met the inclusion criteria. Manual methods evaluating any chin and phasic flexor digitorum superficialis (FDS) activity had the highest DOR (138.8, 95% CI = 21.8% to 881.7%) and AUC (0.9686). The automatic REM atonia index (RAI) showed similar or higher sensitivity (89.1%, 95% CI = 84.6% to 92.7%) but a lower specificity (73.5%), DOR (43.1), and AUC (0.9369) than the manual techniques. CONCLUSIONS: In this meta-analysis, manual RWA quantification that employed chin or phasic FDS activity had the best RBD diagnostic performance. The automatic RAI method may be useful for screening patients with RBD. The results should be interpreted carefully because of the high risk of bias in patient selection and significant heterogeneity among the studies. PROSPERO REGISTRATION NUMBER: CRD42021276445.

Isolated rapid eye movement sleep behavior disorder combined with obstructive sleep apnea: response to treatment and its associated factors.

OBJECTIVE/BACKGROUND: When isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is combined with obstructive sleep apnea (OSA), the pattern of temporal association between REM without atonia (RWA) and apnea-hypopnea events may be related to improvements in RBD symptoms after positive airway pressure (PAP) treatment. We evaluated the frequency of improvement in RBD symptoms after PAP and the relationship of the degree of co-occurrence between RWA and apnea-hypopnea events to RBD symptom improvement after PAP treatment. PATIENTS/METHODS: In an institutional cohort with sleep disorders, 31 patients with video-polysomnography confirmed iRBD and concomitant OSA with an apnea-hypopnea index (AHI) of ≥15/h who received PAP treatment were included. Along with gross video-polysomnography parameters such as AHI and electromyography activity index during REM sleep, a mini-epoch-based parameter apnea-hypopnea-electromyography activity ratio (AH EMG activity ratio) was used to evaluate the co-occurrence between RWA and apnea-hypopnea events. Improvement in RBD symptoms after PAP treatment was designated as a clinical global impression-improvement (CGI-I) score of 0-3 at three-month. RESULTS: Twenty-three (74.2%) patients exhibited improvement in RBD symptoms after PAP treatment. No patient was taking an antidepressant medication. An AH EMG activity ratio of ≥15% (Odds ratio [OR] 10.146, 95% CI 1.302-79.032, P = 0.027) was significantly associated with clinical improvement after PAP treatment in a regression model adjusted for age, sex, AHI, and electromyography activity index during REM. CONCLUSIONS: Treatment of concomitant OSA with PAP can improve symptoms of iRBD. Respiratory events that co-occur with RWA may predict improvement in RBD symptoms after PAP treatment.