REM Sleep Without Atonia Research Articles

Validation of electronic diagnostic codes for rapid eye movement sleep behavior disorder.

Jones MB, Schenck CH, Azarian M, Jorge RE, Sharafkhaneh A, Razjouyan J. Validation of electronic diagnostic codes for rapid eye movement sleep behavior disorder. J Clin Sleep Med. 2024;20(8);1387-1389.

Comparison of quantitative REM without atonia parameters in isolated REM sleep behavior disorder and early untreated Parkinson's disease

ObjectivesTo analyze REM sleep without atonia (RWA) metrics in patients with isolated REM sleep behavior disorder (iRBD), Parkinson's disease (PD) and healthy subjects and compare them in terms of degree of presumed brainstem damage. MethodsForty-nine iRBD patients, 62 PD patients and 38 healthy controls were included into the analysis. Detailed polysomnographic and clinical data including motor, olfactory, autonomic, and cognitive assessment were obtained in all participants and subsequently compared within groups without RBD (i.e., healthy controls, PD-RBD-) and with RBD (i.e., iRBD, PD-RBD+). SINBAR criteria were used to score RWA. ResultsTwenty-one PD patients (33.8 %) had RBD. When comparing PD-RBD-patients and controls, RWA tonic (p = 0.001) and RWA mixed (p = 0.03) were higher in PD-RBD-group. PD-RBD-patients had worse olfactory function than controls (p < 0.001); no significant difference in autonomic or cognitive function was registered. There were no significant differences in RWA parameters when comparing iRBD and PD-RBD + groups. iRBD patients had better olfactory function than PD-RBD+ (p = 0.006); no significant difference in autonomic or cognitive function was registered. PD-RBD + had worse autonomic (p = 0.006) and olfactory (p = 0.001) but not motor and cognitive function compared to PD-RBD-. ConclusionsUntreated de-novo PD patients without RBD have increased RWA metrics compared to healthy subjects indicating subclinical degeneration of brainstem nuclei responsible for RWA. iRBD patients do not differ in RWA metrics from untreated de-novo PD patients with premotor RBD suggesting a similar level of brainstem degeneration caudal to substantia nigra in both groups. Groups with RBD are associated with autonomic dysfunction.

Automated Analysis of REM Sleep without Atonia in the Lewy Body Disease Spectrum

AbstractBackgroundQuantitative rapid eye movement (REM) sleep without atonia (RSWA) recorded during polysomnography (PSG) represents loss of normal REM sleep atonia. RSWA is the neurophysiologic signature of REM sleep behavior disorder (RBD). Visually scored RSWA is a candidate biomarker for synucleinopathies. However, visual RSWA scoring requires expert scoring, limiting widespread application. We comparatively analyzed RSWA in DLB and iRBD using the automated Ferri REM Atonia Index (RAI).MethodWe quantitatively analyzed the RAI in 12 DLB and 20 iRBD patients, compared to 20 controls using Hypnolab Software for Sleep Analysis (SWS Soft, Inc, Colognola ai Colli, Italy). PSG data were converted to European Data Format (.EDF), and the submentalis surface electromyogram (EMG) signal was notch‐filtered at 60 Hertz and rectified. Automatically calculated RAI scores were comparatively analyzed across groups (DLB, iRBD, controls) using Kruskal Wallis H tests for group comparisons, and regression analyses determined relationships between diagnosis, age, and sex. Logistic regression ROC determined optimal RAI for distinguishing iRBD from DLB. When interpreting RAI, lower values represent greater amounts of RSWA, and higher values represent more normal REM atonia.ResultMean age was older in DLB than in iRBD or controls (72.6 vs. 68.7 vs. 66.5 years). All 12 DLB participants were men, the iRBD group had 18 men and 2 women, and controls were comprised of 16 men and 4 women. Mean RAI was lowest in DLB (0.46), intermediate in iRBD (0.71) and highest in controls (0.96), indicating a gradient in RSWA amounts from DLB patients (highest) to controls (lowest) (Figure). Regression demonstrated diagnosis independently predicted RAI, controlling for age and sex (adjusted R2 = 0.49, p = 0.0001). The RAI that optimally distinguished iRBD from DLB was 0.46 (specificity 85%, sensitivity 58%, AUC = 0.75).ConclusionThe RAI demonstrated a clear gradient throughout the Lewy body spectrum; highest (indicating lowest RSWA amounts) in controls, intermediate in iRBD, and lowest (indicating greatest RSWA) in DLB. The RAI is a promising, time efficient and broadly applicable candidate biomarker for DLB and iRBD. Automated quantitative RSWA could be a valuable tool for deep phenotyping throughout the Lewy body disease spectrum.

Overnight Distribution of REM Sleep Features in People with Parkinson's Disease (PD) and Non-PD Controls.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a leading predictor of Parkinson's disease (PD). Diagnosis is performed in the sleep laboratory by detecting pathological REM sleep without atonia (RSWA). The evidence on the overnight distribution of RSWA% is conflicting. To investigate the temporal distribution of the number of ocular movements per REM sleep minute (REM density), and RSWA% in people with PD and non-PD controls. All participants underwent a single overnight evaluation in a sleep laboratory. Clinical evaluation was performed on a separate day. REM density and RSWA% were compared between PD and controls both across four sleep periods and individual REM cycles. A total of 51 participants with recorded RSWA in polysomnography laboratory were included, 28 with PD aged 64±9 years with a disease duration of 3.3±2.9 years, and 23 controls aged 55±8 years. People with PD had lower REM density and higher RSWA% compared to controls. As expected, REM density was higher towards the morning. In contrast, RSWA% was equally distributed across the night, for both PD and controls. PD pathology affects REM sleep features, but not the overnight distribution of those features. While REM density increased towards the end of the night, RSWA% was equally distributed across the night for both PD and controls. Our findings have clinical implications for diagnosing RBD, as quantification of RSWA% in any sleep cycle is sufficient for reliably evaluating total RSWA% and reduced REM density may be a marker of PD.

A Study on the Evaluation of Brainstem Dysfunction in Rapid Eye Movement Sleep Behavior Disorder Using Video Nystagmography

Background: This study aimed to differentiate video nystagmography (VNG) characteristics, including the video head impulse test (vHIT), in patients with idiopathic rapid eye movement behavior disorder (RBD) from healthy controls, which is considered a precursor to degenerative diseases.Methods: One hundred eighty-five patients underwent overnight polysomnography (PSG) and VNG. Based on overnight PSG, 27 patients with RBD or REM sleep without atonia (RWA) and AHI&lt;15 were categorized into the RBD group, 34 patients with RBD/RWA and AHI≥15 were grouped into the combined group. Sixty patients with AHI≥15 and no RBD/RWA were included in the obstructive sleep apnea (OSA) group, and 64 negative participants were assigned to the control group. In VNG, we measured the gain of vHIT in each canal, with the latency, amplitude, and velocity of horizontal saccades and smooth pursuit. We compared the results between groups using ANOVA, after normalization and adjustment for age and sex.Results: The gain of vHIT in the left horizontal canal was decreased in the RBD group, but it was more pronounced in the OSA group. Elevated gain of the left posterior canal was seen in the RBD group, but technical errors were attributable. The RBD group displayed prolonged latency of saccade on the left side and slowed saccade on the right side, but these were statistically insignificant.Conclusions: The VNG study revealed differences between the sleep disorders, potentially reflecting brainstem function in each disorder. However, these differences lacked statistical significance. We anticipate that significant results could be obtained with more controlled conditions.

REM Behavior Disorder: Implications for PD Therapeutics.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia that occurs during REM sleep, characterized by REM sleep without atonia (RSWA) and dream enactment behavior (DEB). RBD is associated with several diseases and medications but most notably is a prodromal feature of synucleinopathies, including Parkinson's disease (PD). This article reviews RBD, its treatments, and implications for PD therapeutics. Recent research recognizes RBD as a prodromal marker of PD, resulting in expansion of basic science and clinical investigations of RBD. Current basic science research investigates the pathophysiology of RBD and explores animal models to allow therapeutic development. Clinical research has focused on natural history observation, as well as potential RBD treatments and their impact on sleep and phenoconversion to neurodegenerative disease. RBD serves as a fresh access point to develop both neuroprotective and symptomatic therapies in PD. These types of investigations are novel and will benefit from the more established basic science infrastructure to develop new interventions.

Contemporary diagnostic visual and automated polysomnographic REM sleep without atonia thresholds in isolated REM sleep behavior disorder.

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. 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. 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%). 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. Leclair-Visonneau L, Feemster JC, Bibi N, etal. 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.

SViT: A Spectral Vision Transformer for the Detection of REM Sleep Behavior Disorder.

REM sleep behavior disorder (RBD) is a parasomnia with dream enactment and presence of REM sleep without atonia (RSWA). RBD diagnosed manually via polysomnography (PSG) scoring, which is time intensive. Isolated RBD (iRBD) is also associated with a high probability of conversion to Parkinson's disease. Diagnosis of iRBD is largely based on clinical evaluation and subjective PSG ratings of REM sleep without atonia. Here we show the first application of a novel spectral vision transformer (SViT) to PSG signals for detection of RBD and compare the results to the more conventional convolutional neural network architecture. The vision-based deep learning models were applied to scalograms (30 or 300 s windows) of the PSG data (EEG, EMG and EOG) and the predictions interpreted. A total of 153 RBD (96 iRBD and 57 RBD with PD) and 190 controls were included in the study and 5-fold bagged ensemble was used. Model outputs were analyzed per-patient (averaged), with regards to sleep stage, and the SViT was interpreted using integrated gradients. Models had a similar per-epoch test F1 score. However, the vision transformer had the best per-patient performance, with an F1 score 0.87. Training the SViT on channel subsets, it achieved an F1 score of 0.93 on a combination of EEG and EOG. EMG is thought to have the highest diagnostic yield, but interpretation of our model showed that high relevance was placed on EEG and EOG, indicating these channels could be included for diagnosing RBD.

Expert Opinion on Current Polysomnography Procedure for Diagnosis of Rapid Eye Movement Sleep Behavior Disorder in Korea

Rapid eye movement (REM) sleep behavior disorder (RBD) is diagnosed based on a history of dream-enactment behavior and documentation of REM sleep without atonia (RWA) on polysomnography (PSG). RWA can be quantified using various methods. To establish comprehensive and clear PSG criteria for diagnosing RBD, the International RBD Study Group (IRBDSG) has recently published guidelines, which include the use of a video-PSG technical setup, REM sleep staging, RWA scoring, video and audio recording and analyses, and a video-PSG procedure for the diagnosis and identification of the prodromal stages of neurodegenerative diseases. Although the guidelines can identify patients with homogeneous RBD, their applicability in a real-world setting, particularly in Korea, presents challenges. Therefore, the aim of the present study was to evaluate and introduce IRBDSG guidelines and results of Korean sleep experts’ opinion survey for diagnosing RBD based on PSG findings.

Differential diagnosis of sleep laughter: A case report and literature review

Sleep laughter is a relatively common phenomenon. It is classically seen during REM sleep, which is associated with dreams, and may be a component of REM sleep without atonia (RWA) as seen in cases of REM sleep behavior disorder (RBD). However, repetitive laughter episodes during NREM or during sleep-wake transition have not been described in the literature.We present a case of paroxysmal laughter out of drowsiness and NREM sleep, occurring almost every night, prompting evaluation for a possible seizure disorder. Multiple tests were unrevealing, including brain magnetic resonance imaging, polysomnogram, multiple sleep latency test and electroencephalogram. However, despite the lack of diagnostic certainty, this case provoked a discussion of key factors distinguishing parasomnia from seizure, which is useful for all physicians who may be faced with a case of unusual behavior in sleep.This case highlights the challenges that are encountered when trying to classify certain unusual sleep-related paroxysmal events.

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

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. 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. 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. 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. CRD42021276445.

Magnetic susceptibility changes in the brainstem reflect REM sleep without atonia severity in isolated REM sleep behavior disorder

REM sleep without atonia (RWA) is the hallmark of isolated REM sleep behavior disorder (iRBD) and is caused by neurodegeneration of brainstem structures. Previously, quantitative susceptibility mapping (QSM) was shown to detect microstructural tissue changes in neurodegenerative diseases. The goal of the study was to compare brainstem magnetic susceptibility (MS) in iRBD and controls using the voxel-based QSM approach and to examine the association between brainstem MS and severity of RWA in iRBD. Sixty iRBD patients and 41 healthy controls were included in the study. Phasic, tonic, mixed RWA and SINBAR score was quantified. QSM maps were reconstructed with QSMbox software from a multi-gradient-echo sequence acquired at 3T MRI system and normalized using a custom T1 template. Voxel-based analysis with age and gender as covariates was performed using a two-sample t-test model for between-group comparison and using a linear regression model for association with the RWA parameters. Statistical maps were generated using threshold free cluster enhancement with p-value p < 0.05, corrected for family wise error. Compared to controls, the iRBD group had higher MS in bilateral substantia nigra (SN), red nucleus and the ventral tegmental area. MS positively correlated with iRBD duration in the right pedunculotegmental nucleus and white matter of caudal mesencephalic and pontine tegmentum and with phasic RWA in bilateral SN. QSM was able to detect MS abnormalities in several brainstem structures in iRBD. Association of MS levels in the brainstem with the intensity of RWA suggests that increased iron content in SN is related to RWA severity.

Video polysomnographic analysis of elevated EMG activity and rapid eye movements before abnormal behaviors in REM sleep behavior disorder.

The pathogenesis of rapid eye movement (REM) sleep behavior disorder (RBD) is unclear. According to the cortical hypothesis, severe RBD episode (RBDE) occurs when spinal motoneurons are less inhibited and cortical and limbic systems are more active. We made this study to prove the hypothesis for the development of RBDE using video-polysomnography (VPSG). VPSG records of 35 patients with RBD were analyzed. According to severity, RBDEs were classified into three motor events (MEs): ME 1; small movements or jerks, ME 2; proximal movements including violent behavior, and ME 3; axial movements including bed falls. For each ME, we measured the number of MEs preceded or not preceded by both REM sleep without atonia (RWA) and REMs during the 10-s-period immediately before ME onset. In severe RBDE (ME 3), the number of MEs preceded by both RWA and REMs was significantly higher than that of MEs not preceded by both (0.8 vs. 0.2, P = 0.033). This was not the case for mild RBDE (ME 1) and moderate RBDE (ME 2). Our results suggest that both RWA and REMs are associated with the development of severe RBDE.

0704 A PSG Study of the Effect of Clonazepam and Melatonin on REM Sleep without Atonia in Isolated REM Sleep Behavior Disorder

Abstract Introduction Although very few prospective clinical trials are available assessing the benefits of drugs in isolated REM sleep behavior disorder (iRBD), clonazepam and melatonin are considered as the first-line treatment options. However, while evidence supporting the efficacy of these two compounds on the clinical behavioral outcomes seems to be clear, it is not clear if they are able to significantly modify the main polysomnographic (PSG) feature of iRBD, i.e. REM sleep without atonia (RSWA). For this reason, we carried-out an observational cross-sectional retrospective PSG study of the effects of clonazepam and melatonin on RSWA. Methods A total of 83 iRBD patients (70 males and 13 females, age range 50.9-83.2 years) were enrolled in this study: 43 drug-free, 21 patients taking at bedtime chronically (&amp;gt;6 months) clonazepam (0.5-2 mg), seven patients taking melatonin extended-release alone (2-3 mg), and 12 taking a combination of clonazepam and melatonin extended-release (same doses as above). PSG studies were assessed for all subjects, including the measurement of the automatic REM sleep atonia index (RAI) and periodic leg movements during sleep, as well as a series of demographic and clinical variables, such as age, age at onset, disease duration, clinical global impression scale (severity and improvement), mini-mental state evaluation, and RBD severity scale. Results None of the outcomes considered in this study showed significant differences between the groups considered. All showed low average values of RAI, as expected, and there were no differences between patients taking clonazepam, melatonin, or a combination of them (drug-free 0.778±0.184, clonazepam 0.797±0.183, clonazepam+melatonin 0.692±0.224, melatonin 0.673±0.228; ANOVA F = 1.329, p = 0.271), despite the clinical global impression scale-improvement was reported to be “much improved” or “minimally improved” in all treated patients. Conclusion This study confirms our previous findings in smaller patient series taking only clonazepam and suggest that both clonazepam and melatonin might be beneficial on some clinical manifestations of iRBD but are unable to modify its underlying neurophysiology. This might also indicate that these agents do not seem to interfere with the core mechanisms of this disease and other disease modifying drugs need to be discovered for iRBD. Support (if any)

0982 Atrial fibrillation diagnosed from a home-based sleep study in a patient with REM behavior disorder

Abstract Introduction Atrial fibrillation (A-Fib) is the most common form of cardiac arrhythmia and is a major cause of stroke. Obstructive sleep apnea (OSA) is an established risk factor of A-Fib, but sleep disruption with frequent awakenings was recently identified as another risk factor, independent from OSA. Home sleep apnea test (HSAT) is widely used to diagnose OSA with low cost and short wait time, and HSAT that uses peripheral arterial tonometry (PAT) can reveal cardiac arrhythmia. Here we report a case of A-Fib detected by PAT-based HSAT in a patient with REM sleep disorder. Report of case(s) A 60-year-old man with hypertension, depression, anxiety, tobacco and alcohol use disorders presented to sleep clinic for frightening vivid dreams and violent dream enactments that gradually developed over the last two years. A diagnostic polysomnography study showed mild OSA, normal heart rhythm, and no epoch of REM sleep without atonia (RSWA). In the following four years, he used CPAP therapy, imagery rehearsal therapy, high-dose melatonin, doxepin and hydroxyzine. However, the frightening dreams and dream enactments persisted despite full adherence to CPAP. To reassess OSA, the patient took a PAT-based HSAT, which showed not only mild OSA, but one episode of irregularly irregular PAT-derived pulsation variations that lasted three hours and started and stopped abruptly. We therefore ordered longitudinal cardiac monitoring, which showed multiple asymptomatic episodes of A-Fib during nighttime. After treatments for A-Fib were started, a polysomnography study with effective CPAP titration showed one episode of A-Fib with rapid ventricular response that lasted 2.5 hours during non-REM sleep, and multiple epochs of RSWA. The diagnosis of REM sleep behavior disorder (RBD) was thus established. Conclusion We reported concurrent developments of RBD and asymptomatic paroxysmal A-Fib in a man in his early sixties. Our case suggests a potential association between RBD and A-Fib, which has not been studied but is conceivable, given that RBD causes frequent awakenings with surges of sympathetic activity. Our case also highlights the advantage of PAT in capturing not only OSA but cardiac arrhythmia. Clinical interpreters of PAT-based HSAT can seize the opportunity to diagnose A-Fib and prevent stroke. Support (if any)

Psychobehavioural profile in narcolepsy type 1 with and without REM sleep behaviour disorder.

REM sleep behaviour disorder (RBD) is common in narcolepsy type 1 (NT1). Abnormalities in the reward system have been observed in NT1, possibly related to impaired orexin projections towards the mesolimbic reward system, but also in RBD when associated with Parkinson's disease. Our study aimed to explore the psychobehavioural profile of NT1 patients with and without RBD compared with healthy controls (HC). Forty patients with NT1 were compared with 20 sex- and age-matched HC. All patients with NT1 underwent a video-polysomnography including a measure of REM sleep without atonia (RSWA). The following neuropsychobehavioural variables were assessed: apathy, impulsivity, depression, cognition, subjective and objective attention, sensation-seeking, and behavioural addictions. The patient population included 22 patients with NT1-RBD and 18 patients with NT1-noRBD. Compared with the healthy controls, patients with NT1 had higher scores of apathy, impulsivity, and depression; a lower score on global cognition, and poorer self-perceived attention. No differences were found between patients with NT1 with and without RBD in all neuropsychological variables, except for impaired objective attention in patients with NT1-RBD. In patients with NT1, a positive correlation was observed between RSWA and both apathy and impulsivity subscale. Moreover, in patients with NT1-RBD, RSWA was positively correlated with depression. Patients with NT1 showed higher depression, apathy, and impulsivity compared with controls. These measures correlate with the severity of RSWA, suggesting a transdiagnostic association between RBD and abnormalities of the reward system at least for patients with NT1.

Ikelos-RWA. Validation of an Automatic Tool to Quantify REM Sleep Without Atonia.

Study Objectives. To present and evaluate an automatic scoring algorithm for quantification of REM-sleep without atonia (RWA) in patients with REM-sleep behaviour disorder (RBD) based on a generally accepted, well-validated visual scoring method, ("Montreal" phasic and tonic) and a recently developed, concise scoring method (Ikelos-RWA). Methods. Video-polysomnographies of 20 RBD patients (68.2 ± 7.2 years) and 20 control patients with periodic limb movement disorder (65.9 ± 6.7 years) were retrospectively analysed. RWA was estimated from chin electromyogram during REM-sleep. Visual and automated RWA scorings were correlated, and agreement (a) and Cohen's Kappa (k) calculated for 1735 minutes of REM-sleep of the RBD patients. Discrimination performance was evaluated with receiver operating characteristic (ROC) analysis. The algorithm was then applied on the polysomnographies of a cohort of 232 RBD patients (total analysed REM-sleep: 17,219 minutes) and evaluated, while correlating the different output parameters. Results. Visual and computer-derived RWA scorings correlated significantly (tonic Montreal: rTM = 0.77; phasic Montreal: rPM = 0.78; Ikelos-RWA: rI = 0.97; all p < 0.001) and showed good to excellent Kappa coefficients (kTM = 0.71; kPM = 0.79; kI = 0.77). The ROC analysis showed high sensitivities (95%-100%) and specificities (84%-95%) at the optimal operation points, with area under the curve (AUC) of 0.98, indicating high discriminating capacity. The automatic RWA scorings of 232 patients correlated significantly (rTM{I} = 0.95; rPM{I} = 0.91, p < 0.0001). Conclusions. The presented algorithm is an easy-to-use and valid tool for automatic RWA scoring in patients with RBD and may prove effective for general use being publicly available.

The Accuracy and Reliability of Sleep Staging and Sleep Biomarkers in Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder.

This study aimed to establish the diagnostic accuracy of a previously validated sleep staging system in patients with probable isolated REM sleep behavior disorder (iRBD), and to compare physicians' diagnoses of iRBD based on REM sleep without atonia (RSWA) to non-REM hypertonia (NRH), a sleep measure independently associated with Parkinsonian spectrum disorders. Twenty-six patients with a history of dream enactment behavior underwent a diagnostic PSG with simultaneous Sleep Profiler (SP) acquisition at two sites. PSG and SP records were sleep staged, and two sleep neurologists independently diagnosed iRBD based on the presence or absence of polysomnographic identified RSWA. Comparisons for PSG vs SP sleep staging and the qualitative presence or absence of PSG-based RSWA vs automated SP-detected NRH was performed using kappa coefficients (k), positive and negative percent agreements (PPA and NPA), and chi-square tests. The kappa scores from Sites-1 and -2 for PSG vs SP staging were different for Wake (k=0.82 vs 0.65), N2 (k=0.63 vs 0.72) and REM (k=0.83 vs.0.72). The by-site kappa values for stage N3 increased from 0.72 and 0.37 to 0.88 and 0.74 after PSG records were reedited. The kappa values for between-physician agreement in iRBD diagnoses were fair (k = 0.22). The agreement between each physician's iRBD diagnoses and NRH were also fair (k=0.29 and 0.22). Abnormal NRH agreed with at least one physician's iRBD diagnosis in 83% of the records. The PPA resulting from between-physician iRBD agreement was stronger and the NPA weaker than the values obtained from comparison of each physician's iRBD diagnosis and abnormal NRH. The potential utility of RSWA and stage N3 as neurodegenerative disorder biomarkers was influenced by between-site variability in visual scoring. The degree to which NRH was associated with iRBD was similar to the between-physician agreement in their diagnosis of iRBD using RSWA.

Severity of REM sleep without atonia correlates with measures of cognitive impairment and depressive symptoms in REM sleep behaviour disorder.

This study aimed to correlate REM sleep without atonia (RSWA) and neuropsychological data in patients with idiopathic/isolated REM sleep behaviour disorder (iRBD) and those with RBD associated with Parkinson's disease (PDRBD), in order to assess whether higher degrees of RSWA are related to poorer cognitive performance. A total of 142 subjects were enrolled: 48 with iRBD, 55 with PDRBD, and 39 PD without RBD (PDnoRBD). All participants underwent video-polysomnographic recording, clinical and neuropsychological assessment. RSWA was quantified according to two manual scoring methods (Montréal, SINBAR) and one automated (REM atonia index, RAI). Mild cognitive impairment (MCI) was diagnosed according to diagnostic criteria for MCI in Parkinson's disease. The relationship between neuropsychological scores and RSWA metrics was explored by multiple linear regression analysis and logistic regression models. Patients with iRBD showed significantly lower visuospatial functions and working memory, compared with the others. More severe RSWA was associated with a higher risk of reduced visuospatial abilities (OR 0.15), working memory (OR 2.48), attention (OR 2.53), and semantic fluency (OR 0.15) in the iRBD. In the whole group, a greater RSWA was associated with an increased risk for depressive symptoms (OR 3.6). A total of 57(40%) MCI subjects were found (17 iRBD, 26 PDRBD, and 14 PDnoRBD). Preserved REM-atonia was associated with a reduced odds of multi-domain MCI in the whole study population (OR 0.54). In conclusion, a greater severity of RSWA was associated with an increased risk for poor cognitive performance and depressive mood in patients with RBD. Moreover, higher RAI was associated with a lower risk of multi-domain MCI.

Prognostic biomarkers in prodromal α-synucleinopathies: DAT binding and REM sleep without atonia

BackgroundIsolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a prodromal state of clinical α-synucleinopathies such as Parkinson’s disease and Lewy body dementia. The lead-time until conversion is unknown....