Detection of REM sleep behaviour disorder by automated polysomnography analysis

ObjectiveEvidence suggests Rapid-Eye-Movement (REM) Sleep Behaviour Disorder (RBD) is an early predictor of Parkinson’s disease. This study proposes a fully-automated framework for RBD detection consisting of automated sleep staging followed by RBD identification.MethodsAnalysis was assessed using a limited polysomnography montage from 53 participants with RBD and 53 age-matched healthy controls. Sleep stage classification was achieved using a Random Forest (RF) classifier and 156 features extracted from electroencephalogram (EEG), electrooculogram (EOG) and electromyogram (EMG) channels. For RBD detection, a RF classifier was trained combining established techniques to quantify muscle atonia with additional features that incorporate sleep architecture and the EMG fractal exponent.ResultsAutomated multi-state sleep staging achieved a 0.62 Cohen’s Kappa score. RBD detection accuracy improved from 86% to 96% (compared to individual established metrics) when using manually annotated sleep staging. Accuracy remained high (92%) when using automated sleep staging.ConclusionsThis study outperforms established metrics and demonstrates that incorporating sleep architecture and sleep stage transitions can benefit RBD detection. This study also achieved automated sleep staging with a level of accuracy comparable to manual annotation.SignificanceThis study validates a tractable, fully-automated, and sensitive pipeline for RBD identification that could be translated to wearable take-home technology.     

Gender differences in clinical findings and α-synucleiopathy-related markers in patients with idiopathic REM sleep behavior disorder

BackgroundRapid eye movement (REM) sleep behavior disorder (RBD) is a male-predominant parasomnia. Earlier clinical RBD patient studies showed gender differences of clinical symptoms and polysomnographic (PSG) findings. However, no previous investigated this issue by means of validated severity scales or by neuropsychological examination related to alpha-synucleinopathy. This study elucidates gender differences in clinical, physiological, and neuropsychological findings in Japanese idiopathic RBD (iRBD) patients.MethodsFrom 220 patients with complaint of sleep-related vocalization or behaviors who visited Yoyogi Sleep Disorder Center from June 2003 through December 2016, 43 female (68.7 ± 7.3 yr) and 141 male patients (66.7 ± 6.7 yr) diagnosed as having iRBD by video-polysomnography (v-PSG) were selected. All subjects answered the RBD questionnaire (RBDQ-JP) and underwent olfactory function test (Sniffin' Sticks test) and cognitive function test (MoCA-J).ResultsFemale iRBD patients had later first symptom-witnessed age (sleep-talking 63.2 ± 10.5 yr, behaviors 60.9 ± 8.6 yr) than male patients (sleep-talking 59.1 ± 8.8 yr, behaviors 64.7 ± 8.9 yr). No gender difference was found in age at diagnosis, clinical severity (RBDQ-JP), or olfactory or cognitive function. Regarding electromyogram (EMG) findings during REM sleep, phasic EMG activity was higher in female patients (22.3 ± 17.8% vs. 16.5 ± 16.1%), although no difference was found in tonic EMG activity.ConclusionsAlthough female iRBD patient symptoms were first recognized later than those of male patients, they showed elevated EMG activity during REM sleep and showed deteriorated olfactory and cognitive function similarly to male patients at the first medical consultation. Results suggest that disease progression in female RBD patients is equivalent to that in male patients.     

A data-driven system to identify REM sleep behavior disorder and to predict its progression from the prodromal stage in Parkinson's disease

ObjectivesTo investigate electroencephalographic (EEG), electrooculographic (EOG) and micro-sleep abnormalities associated with rapid eye movement (REM) sleep behavior disorder (RBD) and REM behavioral events (RBEs) in Parkinson's disease (PD).MethodsWe developed an automated system using only EEG and EOG signals. First, automatic macro- (30-s epochs) and micro-sleep (5-s mini-epochs) staging was performed. Features describing micro-sleep structure, EEG spectral content, EEG coherence, EEG complexity, and EOG energy were derived. All features were input to an ensemble of random forests, giving as outputs the probabilities of having RBD or not (P (RBD) and P (nonRBD), respectively). A patient was classified as having RBD if P (RBD)≥P (nonRBD). The system was applied to 107 de novo PD patients: 54 had normal REM sleep (PDnonRBD), 26 had RBD (PD + RBD), and 27 had at least two RBEs without meeting electromyographic RBD cut-off (PD + RBE). Sleep diagnoses were made with video-polysomnography (v-PSG).ResultsConsidering PDnonRBD and PD + RBD patients only, the system identified RBD with accuracy, sensitivity, and specificity over 80%. Among the features, micro-sleep instability had the highest importance for RBD identification. Considering PD + RBE patients, the ones who developed definite RBD after two years had significantly higher values of P (RBD) at baseline compared to the ones who did not. The former were distinguished from the latter with sensitivity and specificity over 75%.ConclusionsOur method identifies RBD in PD patients using only EEG and EOG signals. Micro-sleep instability could be a biomarker for RBD and for proximity of conversion from RBEs, as prodromal RBD, to definite RBD in PD patients.     

Characteristics of early- and late-onset rapid eye movement sleep behavior disorder in China: a case–control study

ObjectiveTo investigate demography and clinic and polysomnographic characteristics in Chinese rapid eye movement (REM) sleep behavior disorder (RBD) patients across onset ages.MethodsNinety consecutive patients fulfilling the criteria for RBD were recruited for study in our sleep center. Patients were separated into early- and late-onset groups according to age when symptoms began (⩽50 and >50 years, respectively). Ninety age- and gender-matched healthy subjects served as controls. All subjects were interviewed for their clinical history, completed an RBD questionnaire, and underwent an overnight video polysomnography assessment. Demographics, comorbidities, scores on the RBD questionnaire, sleep architecture, and EMG activity were compared between the patients and controls and between the early- and late-onset groups.ResultsOf all RBD patients, 63 were male, and mean age of RBD onset was 54.3 ± 15.7 years. In 25 patients (28%), RBD was secondary and associated with neurodegenerative disease, narcolepsy or antidepressant use. Twenty-three patients (26%) had early-onset RBD and 67 (74%) were in the late-onset group. RBD patients had significantly more comorbidities, dreams and dream-enacting behaviors, and poorer sleep quality than did controls. The early-onset group had a high proportion of females (48%) and an increased proportion of cases associated with narcolepsy. The early-onset group also had fewer movements, lower EMG activity during REM sleep, and better sleep quality when compared to the late-onset group. EMG activity was positively correlated with age of onset. The mean follow-up time was 1.57 ± 0.82 years, and four patients in the late-onset group were subsequently diagnosed with neurodegenerative diseases.ConclusionsStratifying patients into early and late-onset RBD revealed different characteristics from those previously described as typical for RBD. EMG activity during REM sleep was positively correlated with age of onset. We suggest that it will be valuable to explore the relationship between age of onset conversion and neurodegenerative diseases.     

Surface EMG activity during REM sleep in Parkinson's disease correlates with disease severity

ObjectivesOver 40% of individuals with Parkinson's disease (PD) have rapid eye movement sleep behavior disorder (RBD). This is associated with excessive sustained (tonic) or intermittent (phasic) muscle activity instead of the muscle atonia normally seen during REM sleep. We examined characteristics of manually-quantitated surface EMG activity in PD to ascertain whether the extent of muscle activity during REM sleep is associated with specific clinical features and measures of disease severity.MethodsIn a convenience sample of outpatients with idiopathic PD, REM sleep behavior disorder was diagnosed based on clinical history and polysomnogram, and severity was measured using the RBD sleep questionnaire. Surface EMG activity in the mentalis, extensor muscle group of the forearms, and anterior tibialis was manually quantitated. Percentage of REM time with excessive tonic or phasic muscle activity was calculated and compared across PD and RBD characteristics.ResultsAmong 65 patients, 31 had confirmed RBD. In univariate analyses, higher amounts of surface EMG activity were associated with longer PD disease duration (srho = 0.34; p = 0.006) and greater disease severity (p < 0.001). In a multivariate regression model, surface EMG activity was significantly associated with RBD severity (p < 0.001) after adjustment for age, PD disease duration, PD severity and co-morbid sleep abnormalities.ConclusionSurface EMG activity during REM sleep was associated with severity of both PD and RBD. This measure may be useful as a PD biomarker and, if confirmed, may aid in determining which PD patients warrant treatment for their dream enactment to reduce risk of injury.     

Comparison between an automatic and a visual scoring method of the chin muscle tone during rapid eye movement sleep

ObjectiveTo compare two different methods, one visual and the other automatic, for the quantification of rapid eye movement (REM) sleep without atonia (RSWA) in the diagnosis of REM sleep behavior disorder (RBD).MethodsSeventy-four RBD patients (mean age, 62.14 ± 9.67 years) and 75 normal controls (mean age, 61.04 ± 12.13 years) underwent one night video-polysomnographic recording. The chin electromyogram (EMG) during REM sleep was analyzed by means of a previously published visual method quantifying the percentage of 30 s epochs scored as tonic (abnormal, ⩾30%) and that of 2 s mini-epochs containing phasic EMG events (abnormal, ⩾15%). For the computer quantitative analysis we used the automatic scoring algorithm known as the atonia index (abnormal, <0.8). The percentage correct classification, sensitivity, specificity, and Cohen kappa were calculated.ResultsThe atonia index correctly classified 82.6% of subjects, similar to the percentage of correct classifications with individual components of the visual analysis (83.2% each for tonic and phasic), and the combined visual parameters (85.9%). The sensitivity and specificity of automatic analysis (84% and 81%) was similar to the combined visual analysis (89% and 83%). The correlation coefficient between the automatic atonia index and the percentage of visual tonic EMG was high (r = −0.886, P < 0.00001), with moderately high correlation with the percentage of phasic EMG (r = −0.690, P < 0.00001). The agreement between atonia index and the visual parameters (individual or combined) was approximately 85% with Cohen’s kappa, ranging from 0.638 to 0.693.ConclusionSensitivity, specificity, and correct classifications were high with both methods. Moreover, there was general agreement between methods, with Cohen’s kappa values in the ‘good’ range. Given the considerable practical advantages of automatic quantification of REM atonia, automatic quantification may be a useful alternative to visual scoring methods in otherwise uncomplicated polysomnograms.     

Difference in severity of sleep apnea in patients with rapid eye movement sleep behavior disorder with or without parkinsonism

ObjectiveRapid eye movement sleep behavior disorder (RBD) is a common sleep disturbance in patients with neurodegenerative disorders. We aimed to compare sleep parameters among the different types of RBD patients.MethodsA total of 122 patients with dream enactment behavior were screened. Of these, 92 patients who were diagnosed with RBD by polysomnography were included in this study. Enrolled patients with RBD were classified into four groups based on the following diagnoses: idiopathic RBD (iRBD); RBD with Parkinson disease (PD-RBD); multiple system atrophy (MSA) with RBD (MSA-RBD); and dementia with Lewy bodies (DLB) with RBD (DLB-RBD). Various clinical and polysomnographic parameters were compared.ResultsAmong the 92 patients with RBD, 35 had iRBD, 25 had PD-RBD, 17 had MSA-RBD, and 15 had DLB-RBD. The mean apnea−hypopnea index of atypical parkinsonism with RBD (AP-RBD) group was 16.2 ± 17.7 events/h (MSA-RBD, 14.0 ± 16.6; DLB-RBD, 18.8 ± 19.1), which was significantly higher than the other groups (p < 0.05). The proportion of patients with 100% supine sleep in the AP-RBD group (44%) was higher than that in the iRBD group (14%; p = 0.030). The proportion of OSA with 100% supine sleep position was significantly higher in the MSA-RBD and DLB-RBD groups than in the iRBD group (p = 0.042 and p = 0.029, respectively).ConclusionOur study demonstrated that patients in the MSA-RBD and DLB-RBD groups had a tendency to sleeping in the supine position and a higher vulnerability to OSA compared to other RBD groups. Further cohort studies are needed to evaluate the influence of these factors on the development of parkinsonism.     

A comparative study of methods for automatic detection of rapid eye movement abnormal muscular activity in narcolepsy

ObjectiveTo evaluate rapid eye movement (REM) muscular activity in narcolepsy by applying five algorithms to electromyogram (EMG) recordings, and to investigate its value for narcolepsy diagnosis.Patients/methodsA modified version of phasic EMG metric (mPEM), muscle activity index (MAI), REM atonia index (RAI), supra-threshold REM EMG activity metric (STREAM), and Frandsen method (FR) were calculated from polysomnography recordings of 20 healthy controls, 18 clinic controls (subjects suspected with narcolepsy but finally diagnosed without any sleep abnormality), 16 narcolepsy type one without REM sleep behavior disorder (RBD), nine narcolepsy type one with RBD, and 18 narcolepsy type two. Diagnostic value of metrics in differentiating between groups was quantified by area under the receiver operating characteristic curve (AUC). Correlations among the metrics and cerebrospinal fluid hypocretin-1 (CSF-hcrt-1) values were calculated using linear models.ResultsAll metrics excluding STREAM found significantly higher muscular activity in narcolepsy one cases versus controls (p < 0.05). Moreover, RAI showed high sensitivity in the detection of RBD. The mPEM achieved the highest AUC in differentiating healthy controls from narcoleptic subjects. The RAI best differentiated between narcolepsy 1 and 2. Lower CSF-hcrt-1 values correlated with high muscular activity quantified by mPEM, sMAI, lMAI, PEM and FR (p < 0.05).ConclusionsThis automatic analysis showed higher number of muscle activations in narcolepsy 1 compared to controls. This finding might play a supportive role in diagnosing narcolepsy and in discriminating narcolepsy subtypes. Moreover, the negative correlation between CSF-hcrt-1 level and REM muscular activity supported a role for hypocretin in the control of motor tone during REM sleep.     

Effects of long-term use of clonazepam on nonrapid eye movement sleep patterns in rapid eye movement sleep behavior disorder

ObjectiveWe aim to analyze in detail the characteristics of nonrapid eye movement (NREM) sleep in drug-free patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). We compare drug-free iRBD patients to both normal controls and drug-free patients with narcolepsy/RBD and evaluate the changes following the long-term use of bedtime clonazepam.Participants and methodsForty-six participants were recruited: 15 with iRBD (13 men, 2 women; mean age, 65.8 ± 4.39 years), 13 with narcolepsy/RBD (10 men, 3 women; mean age, 63.0 ± 6.73 years), and 18 normal controls (10 men, 8 women; mean age 69.4 ± 7.72 years). Sleep was video polysomnographically recorded and the RBD severity scale (RBDSS) was obtained. Chin electromyography (EMG) amplitude was quantitatively assessed and the atonia index was computed. Additionally, NREM sleep instability was evaluated using an automatic quantitative analysis. Participants with iRBD were re-evaluated after 2.75 ± 1.62 years of regular therapy with 0.5 to 1-mg clonazepam at bedtime.ResultsSlow transient electroencephalography (EEG) events were increased in iRBD and decreased in narcolepsy/RBD, while fast transient events decreased in iRBD and increased in narcolepsy/RBD. During rapid eye movement (REM) sleep the atonia index was reduced in both iRBD and narcolepsy/RBD groups and during NREM sleep atonia index was increased in iRBD participants, remaining low in narcolepsy/RBD participants. After long-term therapy with clonazepam, wakefulness after sleep onset was decreased together with an increase in both slow-wave sleep (SWS) and sleep stage 2, in which the latter reached statistical significance; sleep stages 1 and 2 instability significantly decreased and the duration of EEG transients also slightly but significantly decreased. Finally, chin tone was not modified by clonazepam.ConclusionsOur study confirms that clonazepam modifies some aspects of NREM sleep in iRBD participants with a decrease in its instability. Moreover, we also show that a complex modification of sleep chin atonia exists in these participants, which also involves NREM sleep; for iRBD more complex neuropathologic models encompassing REM sleep and NREM sleep mechanisms are needed.     

Severity of idiopathic rapid eye movement sleep behavior disorder correlates with depression and alexithymia

BackgroundDepression and alexithymia often accompany early stages of Parkinson's disease (PD). However, these symptoms in idiopathic rapid eye movement sleep behavior disorder (iRBD) remain incompletely understood. The aim of this study was to compare depression and alexithymia between iRBD patients and healthy controls, and to evaluate the association between clinical RBD severity and severity of depression and alexithymia.MethodsPolysomnography-confirmed iRBD patients (n = 86) and healthy controls (n = 74) were enrolled. Clinical RBD severity was assessed using the RBD questionnaire-Hong Kong (RBDQ-HK). Depression and alexithymia were evaluated by the Beck Depression Inventory (BDI) and the 20-item Toronto Alexithymia Scale (TAS-20), respectively. Multivariate linear regression analysis was performed with adjustments for several covariates to determine the correlations between RBD severity and severity of depression and alexithymia.ResultsBDI scores were significantly higher in the iRBD group (10.6 ± 7.3) than in healthy controls (8.2 ± 6.0, p = 0.024). Higher total RBDQ-HK scores were associated with more severe depression in iRBD patients, even after controlling for confounding variables. iRBD patients exhibited significantly higher TAS-20 scores (45.7 ± 10.4) than healthy controls (42.1 ± 9.8, p = 0.026). Total RBDQ-HK scores were positively correlated with TAS-20 scores independent of BDI scores.ConclusionsPatients with iRBD were more depressed and had more severe alexithymia than healthy controls. Notably, as the clinical severity of RBD increased, both depression and alexithymia worsened.     

Idiopathic REM sleep behavior disorder in the elderly Spanish community: a primary care center study with a two-stage design using video-polysomnography

ObjectiveTo examine the presence and characteristics of idiopathic REM sleep behavior disorder (IRBD) in a representative Caucasian sample from the elderly community of Lleida, Spain, attending primary care centers.MethodsParticipants were individuals aged 60 years or older who underwent routine visits in two primary care centers. They underwent a two-stage study; a validated screening single question for IRBD diagnosis (RBD1Q) followed by, in those who endorsed positive answer, clinical assessment by a neurologist plus video-polysomnography (V-PSG).ResultsOf 539 individuals (56.4% women, mean age 72.86 ± 8.20 years), 28 (5.2%) endorsed positively the RBD1Q. Four of these 28 refused further assessments. Four of the 24 remaining subjects underwent clinical assessment but refused V-PSG. Of the 20 who underwent clinical assessment plus V-PSG, REM sleep was not recorded in four (20%, all four taking antidepressants). V-PSG ruled out RBD in 12 subjects who had obstructive sleep apnea (n = 9), periodic limb movement disorder in sleep (n = 2) and normal sleep (n = 1). IRBD was diagnosed in four individuals giving an estimated prevalence of 0.74% (95% CI = 0.29–1.89). They were three men and one woman between 74 and 82 years of age who never reported dream-enacting behaviors to their doctors because they thought they represented a normal phenomenon despite suffering sleep-related injuries. These patients had history of violent sleep behaviors with an interval between estimated RBD onset and V-PSG of 4.5 ± 4.2 years.ConclusionsIRBD is not uncommon in the elderly community and its demographic and clinical profile is similar to those diagnosed in sleep centers.     

Gender differences in REM sleep behavior disorder: a clinical and polysomnographic study in China

ObjectiveRapid eye movement (REM) sleep behavior disorder (RBD) has been considered a male-predominant parasomnia, and there is little comparative data on potential differences between males and females. Therefore, the aim of our study was to examine and characterize gender difference in RBD.MethodsNinety patients diagnosed with RBD were consecutively recruited from a sleep medicine clinic. All patients were assessed by a RBD questionnaire and overnight video polysomnography. Demographic, clinical data, presence of dreams and dream-enacting behaviors, sleep parameters and electromyographic (EMG) activity were compared for male and female patients with RBD.ResultsFemales were significantly younger than males, both in the mean age of RBD onset (45.3 ± 19.3 vs. 56.2 ± 14.1; p = 0.027) and the mean age at diagnosis (50.4 ± 18.2 vs. 61.1 ± 14.1; p = 0.022). Secondary RBD was 21% in males and 44% in females (p = 0.021). Antidepressant use was more common among females (22%) than males (2%; p = 0.003). There was no significant gender difference in dream content (eg, violent and frightening dreams) of RBD patients. However, females had less dream-enacting behaviors, especially in movement related dreams and falling out of bed. Interestingly, no significant difference was found in the quantification of EMG activity during REM sleep between male and female patients.ConclusionsWe found significant gender differences in demographics, associated comorbidities, and dream-related behaviors in patients with RBD. Female RBD patients reported significantly less behavior during dreams, but there was no significant gender difference in EMG activity during REM sleep.     

Napping and weekend catchup sleep do not fully compensate for high rates of sleep debt and short sleep at a population level (in a representative nationwide sample of 12,637 adults)

IntroductionShort total sleep time (TST < 6 h) is a strong major health determinant that correlates with numerous metabolic, cardiovascular and mental comorbidities, as well as accidents. Our aim was to better understand, at a population level, how adults adapt their TST during the week, and how short sleepers and those with sleep debt and sleep restriction use napping or catching up on sleep during weekends (ie, sleep debt compensation by sleeping longer), which may prevent these comorbidities.MethodsA large representative sample of 12,367 subjects (18–75 years old) responded by phone to questions about sleep on a national recurrent health poll (Health Barometer, Santé Publique France 2017) assessing sleep schedules (TST) at night, when napping, and over the course of a 24-h period while using a sleep log on workdays and weekends. Retained items were: (1) short sleep (TST ≤ 6 h/24 h); (2) chronic insomnia (international classification of sleep disorders third edition, ICSD-3 criteria); (3) sleep debt (self-reported ideal TST – TST > 60 min, severe > 90 min); and (4) sleep restriction (weekend TST – workday TST = 1–2 h, severe > 2 h).ResultsAverage TST/24 h was 6h42 (± 3 min) on weekdays and 7h26 (± 3 min) during weekends. In addition, 35.9% (± 1.0%) of the subjects were short sleepers, 27.7% (± 1.0%) had sleep debt (18.8% (± 0.9%) severe), and 17.4% (± 0.9%) showed sleep restriction (14.4% (± 0.8%) severe). Moreover, 27.4% (± 0.9%) napped at least once per week on weekdays (average: 8.3 min (± 0.5 min)) and 32.2% (± 1.0%) on weekend days (13.7 min (± 0.7 min)). Of the 24.2% (± 0.9%) of subjects with severe sleep debt (> 90 min), only 18.2% (± 1.6%) balanced their sleep debt by catching up on sleep on weekends (14.9% (± 0.8%) of men and 21.5% (± 0.9%) of women), and 7.4% (± 1.2%) of these subjects balanced their sleep debt by napping (7.8% (± 0.5%) of men and 6.6% (± 0.4%) of women). The remaining 75.8% (± 5.4%) did not do anything to balance their severe sleep debt during the week.Discussion and conclusionsShort sleep, sleep debt, and sleep restriction during weekdays affected about one third of adults in our study group. Napping and weekend catch-up sleep only compensated for severe sleep debt in one in four subjects.     

Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder

ObjectiveTo evaluate changes in the expression of clock genes and melatonin levels in patients with idiopathic REM sleep behavior disorder (RBD) as a potential early stage of synucleinopathies.MethodsWe assessed the rhythmicity of circadian clock genes using real time-quantitative polymerase chain reaction and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and nine age-matched controls.ResultsThe RBD patients did not show circadian rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1 remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did not differ between RBD patients and healthy control subjects. Melatonin profile in RBD patients was delayed by 2 h compared to controls, the habitual sleep phases were phase delayed by about 1 h, however no phase shift occurred in any of the clock genes studied. The control group had stable acrophases of melatonin rhythms of approximately 5 h whereas the RBD patients had a more dispersed range over 11 h.ConclusionsOur results suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion. Thus, we argue that circadian system dysregulation could play a role in RBD.     

Two polysomnographic features of REM sleep behavior disorder: Clinical variations insight for Parkinson's disease

IntroductionLoss of REM sleep muscle atonia (RWA) and dream-enactment behavior (DEB) are two associated features of REM sleep behavior disorder (RBD), which is frequently associated with Parkinson's disease (PD). Few studies have examined both DEB and RWA simultaneously in patients with PD. This study aimed to evaluate relationships between RWA, DEB and clinical characteristics of PD.MethodsWe conducted overnight polysomnography in 145 patients with PD. DEB (motor behaviors and/or vocalizations during REM) and increased RWA (IRWA; tonic and phasic chin EMG density ≥ 30% and ≥15%, respectively) were identified. Patients were categorized as clinical RBD (DEB and IRWA), sub-DEB positive (DEB only), subclinical RBD (IRWA only), or normal REM sleep.ResultsPatients with DEB had higher Hoehn and Yahr (H&Y) stage, Unified Parkinson's Disease Rating Scale (UPDRS) III score, levodopa equivalent dose(LEDs), and worse cognition. RWA was associated with H&Y stage, LEDs, cognition, and sleep structure in all patients. PD duration was associated with RWA, but not DEB. The PD patients who exhibited clinical or subclinical RBD, compared to sub-DEB positive, had higher H&Y stage, UPDRS III score and LEDs, lower cognitive score, worse sleep structure than the PD + cREM group.ConclusionBoth DEB and RWA were associated with severity of PD illness. Subclinical RBD might have different disease progression from sub-DEB positive. DEB symptoms may fluctuate or disappear whereas RWA may continue to develop as PD progresses. Differences in the course of DEB and RWA may reflect the difference in the degeneration process of neurodegenerative disorders.     

The influence of sleep disordered breathing in REM sleep behavior disorder

Objectives/backgroundBecause both REM sleep behavior disorder (RBD) and Obstructive Sleep Apnea (OSA) can present with similar symptoms, it is important to understand the influence of OSA in the clinical manifestations of RBD and whether RBD modulates OSA severity. Our objectives were to compare: 1. the intensity of non-motor symptoms between RBD patients with (RBD-OSA) and without OSA (RBD-non-OSA), and 2. polysomnographic features between RBD-OSA and OSA without RBD (OSA-non-RBD) patients.Methods32 RBD cases were divided in two groups according to the presence of moderate to severe OSA [Apnea Hypopnea Index (AIH) > 14] (RBD-OSA vs. RBD-non-OSA). Non-motor symptoms were assessed with Montreal Cognitive Assessment Scale, SCOPA-Sleep and the Non-Motor Symptom Scale (NMSS) for Parkinson's disease. RBD-OSA patients were compared to 20 OSA-non-RBD patients matched for age, AHI and gender.ResultsCompared to RBD-non-OSA (n = 22) patients, RBD-OSA patients (n = 10) showed significantly higher scores in SCOPA-Sleep Daytime and NMSS Attention/Memory, Gastrointestinal and Urinary domains, as well as higher sleep fragmentation, more oxygen desaturation and higher AIH in NREM sleep. RBD-OSA patients presented with less O₂ desaturation, snoring, and BMI when compared to OSA-non-RBD patients.DiscussionOur data suggests that OSA contributes to hypersomnolence, gastro-intestinal, memory, and urinary complaints in RBD patients. RBD patients seem to have a milder OSA phenotype (possible reflecting a protective role conferred by the maintenance of muscle tone during REM sleep) and to be less prone to obesity and snoring than non-RBD patients.     

An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder

ObjectiveTo analyze the differences in sleep structure and nocturnal motor activity between drug-free REM sleep behavior disorder (RBD) patients and those under therapy with clonazepam, and to evaluate the long-term longitudinal changes under continued therapy with clonazepam.MethodsFifty-seven consecutive iRBD patients were recruited (52 men and 5 women, mean age 68.8 ± 6.03 years). Forty-two patients were not taking any medication at the time of the evaluation (iRBD − Clo) while 15 were taking clonazepam (0.5–1 mg) at bedtime (iRBD + Clo). The Clinical Global Impression-Severity (CGI-S) scale was obtained. Sleep was video-polysomnographically recorded and the RBD severity scale (RBDSS) obtained. The chin EMG amplitude was quantitatively assessed and the Atonia Index computed.ResultsDisease duration was significantly longer in iRBD + Clo patients who also showed a lower rate of stage shifts, higher sleep efficiency and lower percentage of wakefulness after sleep onset and of sleep stage 1, and an increased percentage of sleep stage 2. The longitudinal long-term follow up study in a subgroup of 13 patients showed moderately increased total sleep time, sleep efficiency, sleep stage 2, slow-wave sleep and decreased wakefulness after sleep onset and sleep stage 1, under clonazepam treatment. The CGI scale clearly tended to improve after treatment, but no common trend was evident for RBDSS or Atonia Index.ConclusionsThis study provides evidence of important objective effects of clonazepam on NREM sleep in RBD; this data might be very important for the development of new and effective treatments for this condition.     

Does REM sleep behavior disorder change in the progression of Parkinson’s disease?

Objectives/backgroundRapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD.Patients/methodsIn sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years.ResultsAt follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = −0.57,p = 0.04).ConclusionDespite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.     

Revisiting the impact of REM sleep behavior disorder on motor progression in Parkinson's disease

BackgroundEstimation of progression in Parkinson's disease (PD) is useful to guide clinical decisions and to enable patients to plan and manage their life with PD. Rapid eye movement (REM) sleep behavior disorder (RBD) and REM sleep without atonia (RWA) are recognized as early harbingers of neurodegeneration and may precede motor symptoms by years. However, their impact on motor progression remains elusive.MethodsWe retrospectively analyzed polysomnographic and clinical data of 59 PD patients, grouping them into patients with RBD (n = 15), RWA (n = 22) and those with normal muscle atonia (n = 22). We compared the three groups with regard to motor progression, defined as changes in Unified Parkinson's Disease Rating Scale (UPDRS) III values per year, and selected PD specific characteristics.ResultsMotor disability at first visit and time interval between first and last visits were similar between groups. We observed a significantly faster motor progression in PD patients with RBD and RWA than in those with preserved REM sleep atonia.ConclusionOur findings suggest that impaired muscle atonia during REM sleep might represent a marker of faster motor progression in PD.