The relation between abnormal behaviors and REM sleep microstructure in patients with REM sleep behavior disorder

ObjectiveTo investigate the temporal relation between rapid eye movement (REM) sleep microstructure (REMs, EMG activity) and motor events in REM sleep behavior disorder (RBD).MethodsPolysomnographic records of eight patients with RBD were analyzed and compared with those of eight sex- and age-matched controls. We examined sleep microstructure for REM sleep with and without REMs and phasic chin EMG activity and their temporal relation to motor events on video.ResultsAll types of motor events were either more frequent in RBD patients than in controls (P ? 0.007) or present solely in RBD patients. In RBD, major motor events were significantly more frequent during REM sleep with REMs than during REM sleep without REMs (violent, 84.0% vs. 16.0%, P < 0.001; complex/scenic behavior, 78.1% vs. 23.2%, P < 0.001; major jerks, 77.5% vs. 20.3%, P < 0.001), whereas minor motor activity was evenly distributed (54.1% vs. 45.9%, P = 0.889). Controls showed predominantly minor motor activity with rare myoclonic body jerks. The distribution of motor events did not differ between REM sleep with and without REMs (40.9% vs. 59.1%, P = 0.262).ConclusionsIn RBD, major motor activity is closely associated with REM sleep with REMs, whereas minor jerks occur throughout REM sleep. This finding further supports the concept of a dual nature of REM sleep with REMs and REM sleep without REMs and implies a potential gate control mechanism of REM sleep with REMs for the manifestation of elaborate or violent behaviors in RBD.     

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.     

REM and NREM sleep enactment behaviors in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies

Background/objectiveNocturnal sleep enactment behaviors (SEBs) are common in patients affected by Parkinson’s disease (PD), dementia associated with Parkinson’s disease (PDD), and dementia with Lewy bodies (DLB). We investigated the occurrence and neurobiological significance of abnormal SEBs in the context of PD without cognitive decline compared to PDD/DLB patients.MethodsWe evaluated a sample of 139 patients with PD, PDD, or DLB in a cross-sectional survey. One hundred and seventeen patients showing either no cognitive impairment (PD group) or meeting the diagnostic requirements for dementia (PDD/DLB group) underwent video-polysomnography. Seventy subjects (42 males) in whom a clear-cut diagnosis of abnormal sleep-related motor-behavioral episodes was possible were included in the final analysis.ResultsSEBs consisting of RBD or occurring on arousal from NREM or REM sleep were globally more frequent in the dementia group (PDD/DLB) than in the PD group (p = 0.001), the difference being statistically significant for arousal-related episodes (p = 0.002), while a trend emerged for RBD (p = 0.07). Male sex, daytime sleepiness, higher motor impairment, and lower mini-mental score were significantly more frequent with the occurrence of abnormal sleep-related motor-behavioral episodes.ConclusionSEBs in PD, PDD, and DLB may consist of RBD episodes or of arousal-related NREM and REM episodes. These latter are more frequent in patients with PDD/DLB and seem to be mainly related to more advanced stages of disease with a higher degree of cognitive decline.     

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.     

Comparison of severity of obstructive sleep apnea and degree of accumulation of cardiac 123I-MIBG radioactivity as a diagnostic marker for idiopathic REM sleep behavior disorder

ObjectiveWe investigated cardiac ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphic assessment as a supportive diagnostic indicator for idiopathic REM sleep behavior disorder (RBD) complicated by moderate to severe obstructive sleep apnea (OSA).Methods¹²³I-MIBG was intravenously injected in 23 idiopathic RBD patients with AHI < 5/h, 9 idiopathic RBD patients with 5 ? AHI < 15/h, 15 idiopathic RBD patients complicated with moderate to severe OSA with AHI ? 15/h, and 16 moderate to severe obstructive sleep apnea syndrome (OSAS) patients without RBD by polysomnography.ResultsCardiac MIBG uptake based on H/M was significantly decreased in RBD patients with or without OSA compared with patients with moderate to severe OSAS without RBD. ROC analysis revealed that a delayed H/M cut-off value of 1.97 was useful for differentiating idiopathic RBD complicated by moderate to severe OSA from moderate to severe OSAS without RBD.Conclusions¹²³I-MIBG cardiac scintigraphy has the potential to distinguish true RBD from pseudo-RBD associated with OSA. These results are noteworthy because treatment options and follow-up protocols are determined based on evaluation of moderate to severe OSA complicated with RBD, such as overlapping primary sleep disorders.     

REM sleep behavior disorder in 703 sleep-disorder patients: The importance of eliciting a comprehensive sleep history

ObjectivesThe aim of our study was to evaluate the frequency of REM sleep behavior disorder (RBD) in a mixed sleep laboratory population and to assess potential associations. Moreover, we investigated referral diagnoses of patients subsequently diagnosed with RBD and assessed the frequency of incidental RBD.MethodsCharts and polysomnographic reports of 703 consecutive patients comprising the full spectrum of ICSD-2 sleep disorders [501 males, 202 females; mean age, 51.0 ± 14.1 years (range: 10–82 years)] were carefully reviewed. The vast majority of patients were adults (98.7%). Patients were categorized into those with and without RBD. For associations, all concomitant sleep and neurological diagnoses and medications were evaluated.ResultsThirty-four patients (4.8%) were diagnosed with RBD (27 men; 7 women, mean age, 57.7 ± 12.3 years). RBD was idiopathic in 11 patients (1.6%; 9 men) and symptomatic in 23 patients (3.3%; 18 men) secondary to Parkinsonian syndromes (n = 11), use of antidepressants (n = 7), narcolepsy with cataplexy (n = 4), and pontine infarction (n = 1). Six out of 34 patients were referred for suspected RBD, 20 reported RBD symptoms only on specific questioning, and 8 patients had no history of RBD but showed typical RBD behavioral manifestations in the video-polysomnography. Logistic regression analysis revealed significant associations between RBD and the presence of Parkinsonian syndromes (odds ratio [OR] 16.8, 95%CI: 6.4–44.1; P < 0.001), narcolepsy with cataplexy (OR 10.7, 95%CI: 2.9–40.2; P < 0.001), SSRI use (OR 3.9, 95%CI: 1.6–9.8; P = 0.003), and age (OR 1.5/10-year increase, 95%CI: 1.0–2.0; P = 0.039).ConclusionIn this population of 703 consecutive sleep-disorder patients, RBD was uncommon. Its etiology was predominantly symptomatic. The majority of RBD patients reported RBD symptoms on specific questioning only, underlining the importance of eliciting a comprehensive sleep history for the diagnosis of RBD.     

REM sleep behavior disorder in Parkinson disease: Association with abnormal ocular motor findings

BackgroundThe anatomical substrates associated with generalized muscle atonia during REM sleep are located on the pontine tegmentum and medial medulla oblongata. We examined whether patients with REM sleep behavior disorder (RBD) have abnormal ocular movements suggesting brainstem or cerebellar dysfunction in Parkinson's disease (PD).MethodsCross-sectional survey for the existence of RBD and abnormal ocular movements. Ocular movements were examined by video-oculography (VOG).ResultsA total of 202 patients were included in this study. One hundred and sixteen (57.4%) of the 202 patients have clinically probable RBD, and 28 (24.1%) of the 116 with clinically probable RBD patients had abnormal VOG findings suggesting brainstem or cerebellar dysfunction; whereas 86 of the 202 patients did not have clinically probable RBD, and only 7 (8.1%) of the 86 patients had abnormal VOG findings suggesting brainstem or cerebellar dysfunction (P = 0.001).ConclusionThis study suggests that the presence of RBD is associated with more severe or extensive brainstem pathology or different distribution of pathology in PD.     

Polysomnographic findings, video-based sleep analysis and sleep perception in progressive supranuclear palsy

Objectives: To compare subjective sleep perception, sleep architecture, rapid eye movement (REM) sleep without atonia, and REM sleep behavior disorder (RBD) in patients with progressive supranuclear palsy (PSP) to patients with Parkinson’s disease (PD).Methods: A comparative sleep study using the Parkinson’s Disease Sleep Scale (PDSS), the Mini-Mental State Examination (MMSE), and cardiorespiratory polysomnography on two consecutive nights with synchronized video recording. The study was undertaken in a sleep laboratory in a movement disorder center. Forty patients matched for age and cognition with probable PSP (n = 20, aged 71 ± 8 years, MMSE ? 24 in n = 7) and PD (n = 20, aged 69 ± 5 years, MMSE ? 24 in n = 8).Results: PDSS sum scores showed no difference between PSP and PD. PSP patients had significantly lower sleep efficiency (43.0 ± 15.0%) compared to PD patients (62.8 ± 19.1%) (p < 0.0008). Seventeen PSP patients and 19 PD patients had REM without atonia (RWA). Seven PSP patients and 13 PD patients had clinical RBD. The amount of RWA was lower in PSP (14.5 ± 17.3%) than in PD (44.6 ± 31.3%) (p < 0.0007). Eleven PSP and 11 PD patients were newly identified with sleep-disordered breathing (SDB).Conclusions: Polysomnographically recorded sleep is more severely impaired in PSP than in PD. PDSS ratings do not reflect the poorer sleep quality in PSP, possibly pointing to a specific neuropsychological profile. RWA and RBD are present in both neurodegenerative diseases. So far undetected SDB affects more than half of all patients in this study.     

Loss of REM sleep features across nighttime in REM sleep behavior disorder

ObjectivesMelatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep behavior disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects.MethodsAn overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD + RBD+), ten PD patients without RBD (PD + RBD−), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity.ResultsFrom the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change.ConclusionsPatients with PD or iRBD lost the physiologic nocturnal increase in REM sleep duration, and patients with RBD (either with or without PD) lost the increase of REMs frequency across the night, suggesting an alteration in the circadian system in RBD. This supports the hypothesis of a direct effect of melatonin on RBD symptoms by its chronobiotic activity.     

REM sleep without atonia and nocturnal body position in prediagnostic Parkinson's disease

BackgroundSleep disturbances are features of Parkinson's disease (PD), that can already occur before PD diagnosis. The most investigated prodromal PD sleep disorder is REM sleep behavior disorder (RBD). The relation between other polysomnographic (PSG) alterations and the prediagnostic stages of PD, however, is less clear.MethodsWe performed a retrospective case–control study to characterize polysomnographic alterations in PD and prediagnostic PD. We included 63 PD subjects (33 subjects that underwent a video-PSG before PD diagnosis [13 with and 20 without RBD] and 30 subjects that underwent a PSG after PD diagnosis) and 30 controls. PSGs were analyzed for sleep stages, different RSWA variables, body position, arousals, periodic limb movements, and REM density.ResultsHigher subscores of all RSWA variables were observed in subjects with PD and prediagnostic PD (with and without RBD). Total RSWA, tonic RSWA and chin RSWA severity were significant predictors for all PD and prediagnostic PD groups. Our study also shows a higher percentage of nocturnal supine body position in all PD and prediagnostic PD groups. Supine body position percentage is the highest in the PD group and has a positive correlation with time since diagnosis.ConclusionsThese findings suggest that increased total, tonic and chin RSWA as well as nocturnal supine body position are already present in prediagnostic PD, independently of RBD status. Prospective longitudinal studies are necessary to confirm the additional value of these PSG abnormalities as prodromal PD biomarkers.     

REM sleep characteristics of nightmare sufferers before and after REM sleep deprivation

ObjectivesTo examine whether disrupted regulation of REM sleep propensity is implicated in nightmare (NM) pathophysiology.BackgroundHeightened REM propensity induced by REM sleep deprivation is belied by increases in REM %, REM density and the dreamlike quality of dream mentation during post-deprivation recovery sleep. Compromised regulation of REM sleep propensity may be a contributing factor in the pathophysiology of frequent NMs.MethodsA preliminary study of 14 subjects with frequent NMs (?1 NM/week; 27.6 ± 9.9 years) and 11 healthy control subjects (<1 NM/month; 24.3 ± 5.3 years) was undertaken. Subjects completed home sleep/dream logs and underwent three nights of polysomnographic recording with REM sleep deprivation on night 2. Group differences were assessed for a battery of REM sleep and dream measures on nights 1 and 3.ResultsSeveral measures, including #skipped early-night REM periods, REM latency, REM/NREM cycle length, early/late REM density,REM rebound, late-night REM% and dream vividness, suggested that REM sleep propensity was abnormally low for the frequent NM group throughout the 3-day study.ConclusionsFindings raise the possibility that REM anomalies recorded from NM sufferers sleeping in the laboratory environment reflect a disruption of one or more endogenous regulators of REM sleep propensity.     

Longitudinal changes in cognition in early Parkinson's disease patients with REM sleep behavior disorder

IntroductionCognitive decline is common in Parkinson's disease (PD), and identifying patients at highest risk for it is essential. We aimed to examine the effect of possible REM sleep behavior disorder (pRBD) on rate of cognitive decline in early PD, for both global cognition and in specific cognitive domains.MethodsParkinson's Progression Markers Initiative (PPMI) is a multi-site, international study of PD patients untreated at enrollment. pRBD was assessed with the REM sleep behavior disorder questionnaire (RBDSQ). Global cognition was assessed at baseline and annually using the Montreal Cognitive Assessment (MoCA) and a cognitive battery. Linear mixed effects models were used to examine the relationship between pRBD (RBDSQ ≥ 6) and rate of change in cognitive variables. Age, sex, years of education, and baseline motor and cognitive scores were included as covariates.ResultsThe baseline sample consisted of 423 individuals with PD, mean age 61.7 years and 65.5% male. Data was available on 389, 366, and 196 participants at 1-year, 2-year, and 3-year follow-up respectively. Possible RBD occurred in 108 (25.5%) at baseline. In multivariate analyses, baseline RBD was associated with greater annual rate of decline in MoCA score (β = −0.34, 95%CI −0.54, −0.13, p < 0.001), Symbol Digit Modalities Test (β = −0.69, 95%CI −1.3, −0.09, p = 0.024), and Hopkins Verbal Learning Test-Revised, delayed free recall (β = −0.21, 95%CI −0.41, −0.013, p = 0.037).ConclusionsPossible RBD is common in early PD and predicts future cognitive decline, particularly in attention and memory domains.     

Rapid eye movement sleep behaviour disorder in young- and older-onset Parkinson disease: a questionnaire-based study

BackgroundRapid eye movement sleep behavior disorder (RBD) is common in Parkinson disease (PD).ObjectivesTo determine the frequency of clinically probable RBD (cpRBD) in young-onset (21 to ⩽40 years; YOPD) and older-onset PD (>40 years; OOPD) and characterize its pattern.MethodsA total of 156 patients with PD (YOPD-51, OOPD-105) were clinically examined and the presence of RBD was diagnosed using the minimal criteria for diagnosis of RBD (International Classification of Sleep Disorders, ICSD-1). RBD screening questionnaire based on the minimal criteria was used. The bed-partners were also interviewed with Mayo sleep questionnaire. Other scales included Unified Parkinson Disease Rating Scale part III (UPDRS III), Hoehn & Yahr stage, Mini Mental Status Examination, Pittsburgh Sleep Quality Index, Parkinson Disease Sleep Scale, Epworth Sleep Scale, Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale.ResultscpRBD was diagnosed in 30 (19.2%) patients, majority being OOPD rather than YOPD (86.7% vs 13.3%; P = 0.01). The frequency of RBD was significantly higher (P = 0.016) in OOPD (24.8%) compared to those with YOPD (7.8%). Most often (72.4%) RBD occurred after the onset of parkinsonian symptoms. RBD was independently associated with higher global PSQI scores, total ESS scores and total PDSS scores after adjusting for the effects of age, gender, Hoehn & Yahr stage and duration of illness.ConclusionsPatients with RBD were older with later-onset motor symptoms, a more advanced stage, poorer sleep quality, and more frequent daytime sleepiness. Older-onset PD had a higher frequency of RBD than young-onset PD.     

Clinical manifestations of Parkinson disease and the onset of rapid eye movement sleep behavior disorder

ObjectiveTo identify whether the presence and/or timing of rapid eye movement (REM) sleep behavior disorder (RBD) onset were associated with differences in clinical features and sleep parameters of Parkinson disease (PD).MethodsIn all, 112 PD patients were enrolled and all underwent extensive clinical evaluations and video-polysomnography (PSG). Clinical features and PSG parameters were compared in PD patients with (PD + RBD) or without (PD − RBD) RBD, RBD preceding (RBD > PD), or not (PD ⩾ RBD) PD onset.ResultsSixty-three of the 112 PD patients were affected by RBD. Adjusted for age, gender, education, body mass index (BMI), levodopa equivalent daily dose (LED) and PD duration, PD + RBD patients had higher Hoehn & Yahr stage, higher scores for UPDRS parts I, II and III, more dyskinesia, higher ratio of axial/limb manifestations, and more hallucinations. Their cognitive and quality-of-life status was significantly lower (all P < 0.05). For PSG, PD + RBD patients exhibited higher percentages of phasic and tonic EMG activities, lower apnea hypopnea (AHI) and oxygen desaturation index (ODI), and less time in arterial oxygen saturation (SaO₂) <90% during REM sleep (all P < 0.05). PD ⩾ RBD (n = 22) patients did not significantly differ from RBD > PD (n = 41) patients in clinical manifestations, whereas the PD ⩾ RBD subgroup had significantly higher UPDRS part I score, lower PDQ score and lower AHI during REM than the PD − RBD group (all P < 0.05), but not RBD > PD subgroup. Correlation analysis showed that worse cognition was associated with shorter interval of RBD preceding PD onset (r = 0.297, P = 0.018), but not RBD duration (P = 0.202).ConclusionsClinical manifestations of PD may vary depending on the presence and timing of RBD onset. These findings are compatible with the hypothesis that RBD may be a marker of complex subtypes of PD.     

Validation of the Japanese version of the REM sleep behavior disorder questionnaire (RBDQ-JP)

BackgroundThe rapid eye movement (REM) sleep behavior disorder (RBD) questionnaire (RBDQ)-Hong Kong was the first tool developed for quantifying the severity of RBD. This study was conducted to validate the Japanese version of the questionnaire and to investigate its reliability, validity, and responsiveness.MethodsPatients with idiopathic RBD and sex and age-matched healthy controls completed the Japanese version of the questionnaire (RBDQ-JP). In addition to the evaluation of its reliability and validity, the questionnaire scores were compared between those earned before and those earned after pharmaceutical treatment to assess the questionnaire’s responsiveness.ResultsThe questionnaire demonstrated high test–retest reliability and moderate internal consistency. The best cut-off score was 19/20 with a sensitivity of 97.2% and a specificity of 97.5%. Exploratory factor analysis revealed that the questionnaire consists of the following two factors: Factor 1, Dream and dream-related behaviors and Factor 2, Violent/complex behaviors. Among the patients, significant correlation was found between the rate of change of questionnaire score and the clinical global impression improvement score with pharmaceutical treatment (rs = ?0.829, p < 0.01).ConclusionsThe RBDQ-JP provides satisfactory reliability, validity, and responsiveness. The questionnaire is suitable for severity assessment and for assessing the RBD treatment outcome.     

Treatment outcomes in REM sleep behavior disorder

ObjectiveREM sleep behavior disorder (RBD) is usually characterized by potentially injurious dream enactment behaviors (DEB). RBD treatment aims to reduce DEBs and prevent injury, but outcomes require further elucidation. We surveyed RBD patients to describe longitudinal treatment outcomes with melatonin and clonazepam.MethodsWe surveyed and reviewed records of consecutive RBD patients seen at Mayo Clinic between 2008–2010 to describe RBD-related injury frequency–severity as well as RBD visual analog scale (VAS) ratings, medication dosage, and side effects. Statistical analyses were performed with appropriate non-parametric matched pairs tests before and after treatment, and with comparative group analyses for continuous and categorical variables between treatment groups. The primary outcome variables were RBD VAS ratings and injury frequency.ResultsForty-five (84.9%) of 53 respondent surveys were analyzed. Mean age was 65.8 years and 35 (77.8%) patients were men. Neurodegenerative disorders were seen in 24 (53%) patients and 25 (56%) received antidepressants. Twenty-five patients received melatonin, 18 received clonazepam, and two received both as initial treatment. Before treatment, 27 patients (60%) reported an RBD associated injury. Median dosages were melatonin 6 mg and clonazepam 0.5 mg. RBD VAS ratings were significantly improved following both treatments (p_m = 0.0001, p_c = 0.0005). Melatonin-treated patients reported significantly reduced injuries (p_m = 0.001, p_c = 0.06) and fewer adverse effects (p = 0.07). Mean durations of treatment were no different between groups (for clonazepam 53.9 ± 29.5 months, and for melatonin 27.4 ± 24 months, p = 0.13) and there were no differences in treatment retention, with 28% of melatonin and 22% of clonazepam-treated patients discontinuing treatment (p = 0.43).ConclusionsMelatonin and clonazepam were each reported to reduce RBD behaviors and injuries and appeared comparably effective in our naturalistic practice experience. Melatonin-treated patients reported less frequent adverse effects than those treated with clonazepam. More effective treatments that would eliminate injury potential and evidence-based treatment outcomes from prospective clinical trials for RBD are needed.     

Auditory arousal responses and thresholds during REM and NREM sleep of sleepwalkers and controls

BackgroundIt has been suggested that sleepwalkers are more difficult to awaken from sleep than are controls. However, no quantified comparisons have been made between these two populations. The main goal of this study was to assess arousal responsiveness via the presentation of auditory stimuli (AS) in sleepwalkers and controls during normal sleep and recovery sleep following sleep deprivation.MethodsTen adult sleepwalkers and 10 age-matched control subjects were investigated. After a screening night, participants were presented with AS during slow-wave sleep (SWS), REM, and stage 2 sleep either during normal sleep or daytime recovery sleep following 25 h of sleep deprivation. The AS conditions were then reversed one week later.ResultsWhen compared to controls sleepwalkers necessitated a significantly higher mean AS intensity (in dB) to induce awakenings and arousal responses during REM sleep whereas the two groups’ mean values did not differ significantly during SWS and stage 2 sleep. Moreover, when compared to controls sleepwalkers had a significantly lower mean percentage of AS that induced arousal responses during REM sleep while the opposite pattern of results was found during SWS.ConclusionsThe data indicate that sleepwalkers have a higher auditory awakening threshold than controls, but only for REM sleep. These findings may reflect a compensatory mechanism of the homeostatic process underlying sleep regulation during sleepwalkers’ REM sleep in reaction to their difficulties maintaining consolidated periods of NREM sleep.     

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.     

Validation of a new REM sleep behavior disorder questionnaire (RBDQ-HK)

ObjectivesThere are limited screening instruments for diagnosis of REM sleep behavior disorder (RBD) and none for quantifying the severity of disease. We aimed to validate a 13-item self-reported RBD questionnaire (RBDQ-HK) for diagnostic and monitoring purposes.MethodsBased on ICSD-II and our previous clinical and empirical work, the RBDQ-HK questionnaire was designed and administered in patients attending university-affiliated sleep clinic and psychiatric out-patient clinic, and subjects from the general population. ROC curve and exploratory factor analysis were employed to evaluate the scale, which had a score ranging from 0 to 100.ResultsOne hundred and seven RBD patients [mean age 62.6 (15.5) years; male 70.1%] and 107 control subjects [mean age 55.3 (9.0) years, male 57.9%] completed the questionnaire. The diagnoses of all the study subjects were independently ascertained by clinical interview and PSG. RBD patients had a significantly higher total RBDQ-HK score [mean (s.d.): 32.1 (16.1), range 3–71] than the control group [9.5 (10.2), range 0–55] (p < 0.005). The RBDQ-HK demonstrated robust psychometric properties with moderate sensitivity (82.2%), specificity (86.9%), positive predictive value (PPV; 86.3%), and negative predictive value (NPV; 83.0%), high internal consistency and test–retest reliability. Exploratory factor analysis revealed two components (dream-related and behavioral factors) that corresponded to the essential clinical features of RBD. The best cut-off for total score (range 0–100) was at 18/19 and the best cut-off for factor 2 (behavioral factors including sleep talking, shouting, limb movements and sleep-related injuries, range 0–70) was at 7/8.ConclusionsThe RBDQ-HK has satisfactory validity and reliability as a measure of clinical RBD symptoms and severity. It may serve as an effective tool for diagnosis and evaluation of the disease course to facilitate future clinical and research studies.