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.     

A preliminary quantitative analysis of REM sleep chin EMG in Parkinson's disease with or without REM sleep behavior disorder

ObjectivesTo compare REM sleep chin EMG quantitative features between Parkinson’s disease (PD) patients with or without REM sleep behavior disorder (RBD).Subjects and methodsTwenty-seven consecutive PD patients (mean age 67.9 years) and 19 normal controls (mean age 67.5 years) were enrolled. Detailed clinical, laboratory, and polysomnographic studies were obtained in all participants and characteristics of chin electromyographic amplitude during rapid eye movements sleep were analyzed by means of an automatic quantitative approach (Atonia Index).ResultsSixteen of the 27 patients were affected by RBD. An Atonia Index below 0.90 showed high sensitivity (0.938) and specificity (0.909) for the diagnosis of RBD within the group of PD patients.ConclusionThis study recommends the Atonia Index as an objective measure to support and aid the diagnosis of RBD in PD.     

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.     

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.     

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.     

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.     

Decreased sleep spindle density in patients with idiopathic REM sleep behavior disorder and patients with Parkinson’s disease

ObjectiveTo determine whether sleep spindles (SS) are potentially a biomarker for Parkinson’s disease (PD).MethodsFifteen PD patients with REM sleep behavior disorder (PD + RBD), 15 PD patients without RBD (PD − RBD), 15 idiopathic RBD (iRBD) patients and 15 age-matched controls underwent polysomnography (PSG). SS were scored in an extract of data from control subjects. An automatic SS detector using a Matching Pursuit (MP) algorithm and a Support Vector Machine (SVM) was developed and applied to the PSG recordings. The SS densities in N1, N2, N3, all NREM combined and REM sleep were obtained and evaluated across the groups.ResultsThe SS detector achieved a sensitivity of 84.7% and a specificity of 84.5%. At a significance level of α = 1%, the iRBD and PD + RBD patients had a significantly lower SS density than the control group in N2, N3 and all NREM stages combined. At a significance level of α = 5%, PD − RBD had a significantly lower SS density in N2 and all NREM stages combined.ConclusionsThe lower SS density suggests involvement in pre-thalamic fibers involved in SS generation. SS density is a potential early PD biomarker.SignificanceIt is likely that an automatic SS detector could be a supportive diagnostic tool in the evaluation of iRBD and PD patients.     

Parkinson’s disease and REM sleep behavior disorder result in increased non-motor symptoms

ObjectiveRapid eye movement (REM)-sleep behavior disorder (RBD) is often comorbid with Parkinson’s disease (PD). The current study aimed to provide a detailed understanding of the impact of having RBD on multiple non-motor symptoms (NMS) in patients with PD.MethodsA total of 86 participants were evaluated for RBD and assessed for multiple NMS of PD. Principal component analysis was utilized to model multiple measures of NMS in PD, and a multivariate analysis of variance was used to assess the relationship between RBD and the multiple NMS measures. Seven NMS measures were assessed: cognition, quality of life, fatigue, sleepiness, overall sleep, mood, and overall NMS of PD.ResultsAmong the PD patients, 36 were classified as having RBD (objective polysomnography and subjective findings), 26 as not having RBD (neither objective nor subjective findings), and 24 as probably having RBD (either subjective or objective findings). RBD was a significant predictor of increased NMS in PD while controlling for dopaminergic therapy and age (p = 0.01). The RBD group reported more NMS of depression (p = 0.012), fatigue (p = 0.036), overall sleep (p = 0.018), and overall NMS (p = 0.002).ConclusionIn PD, RBD is associated with more NMS, particularly increased depressive symptoms, sleep disturbances, and fatigue. More research is needed to assess whether PD patients with RBD represent a subtype of PD with different disease progression and phenomenological presentation.     

Age,drugs, or disease: What alters the macrostructure of sleep in Parkinson’s disease?

ObjectiveTo describe the alterations in the macrostructure of sleep in a large cohort of sleep-disturbed patients with Parkinson’s disease (PD) and investigate influencing factors.MethodsA cohort of sleep-disturbed but otherwise unselected PD patients (n = 351) was investigated with video-supported polysomnography. We analyzed the influence of age, disease duration, disease severity, and dopaminergic medication on subjective sleep perception, sleep efficiency, the amount of slow wave sleep, awakenings, periodic leg movements in sleep (PLMS), and REM sleep behavior disorder (RBD).ResultsSleep efficiency and slow wave sleep decreased with age (p = 0.003 and p = 0.041, respectively). The number of awakenings and the frequency of RBD increased with age (p = 0.028 and p = 0.006, respectively). Higher Hoehn & Yahr stages were associated with more PLMS (p = 0.017). A higher daily dose of levodopa corresponded to more RBD (p < 0.001). Neither disease duration nor levodopa dosage had any influence on sleep efficiency, slow wave sleep, awakenings, or PLMS. Dopamine agonists increased awakenings (p < 0.001) and lowered PLMS (p < 0.001). Subjective sleep perception was not influenced by any of the factors analyzed. The only path model that could be replicated identified disease severity and dopamine agonists as interdependent factors influencing awakenings and PLMS.ConclusionAge leads to less sleep and a higher risk for RBD, and disease severity increases motor phenomena such as PLMS; dopamine agonists reduce PLMS but increase awakenings. No single factor analyzed influenced subjective sleep perception in this cohort of sleep disturbed PD patients.     

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.     

Electroencephalographic slowing heralds mild cognitive impairment in idiopathic REM sleep behavior disorder

ObjectivePatients with idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) may show electroencephalographic (EEG) slowing reflecting cortical dysfunction and are at risk for developing neurological conditions characterized by cognitive dysfunction including mild cognitive impairment (MCI), dementia with Lewy bodies and Parkinson’s disease with associated dementia. We hypothesized that those IRBD patients who later developed MCI had pronounced cortical EEG slowing at presentation.MethodsPower EEG spectral analysis was blindly quantified from the polysomnographic studies of 23 IRBD patients without cognitive complaints and 10 healthy controls without RBD. After a mean clinical follow-up of 2.40 ± 1.55 years, 10 patients developed MCI (RBD + MCI) and the remaining 13 remained idiopathic.ResultsPatients with RBD + MCI had marked EEG slowing (increased delta and theta activity) in central and occipital regions during wakefulness and REM sleep, particularly in the right hemisphere, when compared with controls and, to a lesser extent, with IRBD subjects who remained idiopathic. The EEG spectral pattern of the RBD + MCI group was similar to that seen in patients with dementia with Lewy bodies and Parkinson’s disease associated with dementia.ConclusionOur findings suggest that the presence of marked EEG slowing on spectral analysis might be indicative of the short-term development of MCI in patients initially diagnosed with IRBD.     

Validation study of REM Sleep Behavior Disorder Questionnaire – Hong Kong (RBDQ-HK) in East China

ObjectiveTo validate the REM Sleep Behavior Disorder (RBD) Questionnaire – Hong Kong (RBDQ-HK) in polysomnography (PSG)-confirmed RBD and non-RBD subjects, and to evaluate its usefulness in different clinical populations.MethodsIn total, 325 subjects (115 RBD and 210 controls) from East China were enrolled. After patients had finished the structured interview, and completed the RBDQ-HK and video-PSG test, we evaluated the reliability of RBDQ-HK (areas under the curves (AUC), the best cut-off values, factor 2 of RBDQ-HK, and overall scale) and validated the usefulness of RBDQ-HK between the Parkinson disease (PD) and obstructive sleep apnea (OSA) groups.ResultsThe best cut-off values for factor 2 of RBDQ-HK were located at 7/8 with a sensitivity of 90% and specificity of 82% (AUC = 0.911), and for RBDQ-HK overall scale were located at 17 with a sensitivity of 85% and specificity of 81% (AUC = 0.892) in all subjects. Both factor 2 and overall scale of RBDQ-HK are valid in all subjects (PD and OSA patients), with a higher accuracy given by factor 2 of RBDQ-HK.ConclusionsRBDQ-HK and its factor 2 are useful and validated RBD screening instruments, and could be used as a tool for screening RBD in patients with PD and OSA.     

Excessive fragmentary myoclonus in Machado–Joseph disease

ObjectiveMachado–Joseph disease (MJD) is a neurodegenerative disease which usually presents several clinical findings including cerebellar ataxia and other extracerebellar features, such as Parkinsonism, dystonia, peripheral neuropathy, and lower motor neuron disease. Some data have demonstrated a high frequency of sleep disorders in these patients, including excessive daytime sleepiness (EDS), insomnia, obstructive sleep apnea (OSA), rapid eye movement (REM) sleep behavior disorder (RBD), and restless legs syndrome (RLS). Herein, we aimed to describe the high frequency of excessive fragmentary myoclonus (EFM) in MJD.Materials and methodsWe recruited 44 patients with MJD and 44 healthy controls. All participants underwent an all-night polysomnography (PSG). EFM was evaluated and defined in accordance to the criteria of the American Academy of Sleep Medicine.ResultsHalf of the MJD patients (n = 22) had EFM diagnosed through PSG, though no healthy control participant presented this finding (P < .0001). In the MJD group, older participants and men had a higher frequency of EFM. There was no correlation between EFM and the following data: body mass index (BMI), apnea–hypopnea index (AHI), EDS, loss of atonia during REM sleep, periodic limb movements during sleep (PLMS), RLS, RBD, ataxia severity, the number of cytosine–adenine–guanine trinucleotide (CAG) repeats, disease duration, sleep efficiency, sleep fragmentation, and sleep stage percentages between patients with or without EFM.ConclusionEFM is highly prevalent in patients with MJD. Our study demonstrates that EFM must be included in the clinical spectrum of sleep disorders in MJD patients.     

Association of sleep with sudden unexpected death in epilepsy

ObjectiveThe objective of this study was to determine the association of sleep with sudden unexpected death in epilepsy (SUDEP).MethodsWe conducted a systematic review and meta-analysis based on literature search from databases PubMed, Web of Science, and Scopus using keywords “SUDEP”, or “sudden unexpected death in epilepsy”, or “sudden unexplained death in epilepsy”. Sudden unexpected death in epilepsy was considered to occur during sleep if the patient was found in bed, if the SUDEP cases were documented as in sleep, or if the patient was found at bedside on the bedroom floor.ResultsCircadian pattern was documented in 880 of the 1025 SUDEP cases in 67 studies meeting the inclusion and exclusion criteria. Of the 880 SUDEP cases, 69.3% occurred during sleep and 30.7% occurred during wakefulness. Sudden unexpected death in epilepsy was significantly associated with sleep as compared to wakefulness (P < 0.001). In the subgroup of 272 cases in which circadian pattern and age were documented, patients 40 years old or younger were more likely to die in sleep than those older than 40 years (OR: 2.0; 95% CI = 1.0, 3.8; P = 0.05). In the subgroup of 114 cases in which both circadian pattern and body position at the time of death were documented, 87.6% (95% CI = 81.1%, 94.2%) of patients who died during sleep were in the prone position, whereas 52.9% (95% CI = 24.7%, 81.1%) of patients who died during wakefulness were in the prone position. Patients with nocturnal seizures were 6.3 times more likely to die in a prone position than those with diurnal seizures (OR: 6.3; 95% CI = 2.0, 19.5; P = 0.002).ConclusionsThere is a strong association of SUDEP with sleep, suggesting that sleep is a significant risk factor for SUDEP. Although the risks of SUDEP associated with sleep are unknown and likely multifactorial, the prone position might be an important contributory factor.     

REM sleep behaviour disorder (RBD) and its associations in young patients

Study objectivesTo retrospectively examine the characteristics of a population of patients <50 years of age with clinical and polysomnographic features diagnostic for RBD.MethodsReview of our sleep centre’s database for patients with RBD diagnosed over the last 7 years. Ninety-one patients were separated into two groups according to their age at the time of diagnosis (<50 y and ?50 y). Clinical and polysomnographic data were reviewed.ResultsSixty-two were male; mean age was 52 ± 19 y. Thirty-nine were <50 y. In the group <50 y there was a male predominance but in a smaller proportion (M:F = 1.4:1) compared with the group ?50 (M:F = 3:1). Seventy-six patients complained of abnormal behaviour (AB) during sleep, 12 with narcolepsy complained of excessive daytime sleepiness (EDS) with the AB being elicited only during consultation, and three complained of both EDS and AB. All patients, except one in the group ?50, described AB related to vivid dreams with violent content. The majority of the patients had the idiopathic form of RBD in both groups (51.2% group <50, 63.4% group ?50). The secondary form was associated with narcolepsy in 38.4% of patients in the group <50 y and with a synucleinopathy in 28.8% of patients in the group ?50. A strong association was noted between RBD and non-REM parasomnias.ConclusionsIn a population of patients with RBD presenting to a regional sleep laboratory, more than one-third of patients were <50 y at time of diagnosis. The commonest associated disorder was narcolepsy in patients <50 y, and synucleinopathy in those ?50 y. The coexistence of RBD with a NREM parasomnia was not uncommon in cases of idiopathic RBD affecting patients <50 y.     

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.     

Relationship between insomnia and pain in major depressive disorder: A sleep diary and actigraphy study

ObjectivesInsomnia and pain are frequent complaints during the course of a major depressive episode. We analyzed the association between insomnia and pain symptoms using subjective and objective sleep measures.MethodsThis is a prospective, naturalistic follow-up study in a university-based psychiatric unit. Ninety-one Chinese patients were enrolled during an acute episode of major depressive disorder (mean age = 48 years, 73 women); 82 of them were reassessed 3 months later using the same assessment on sleep, pain, depressive, and anxiety symptoms. Clinician-rated insomnia symptoms were obtained using the insomnia items of the Hamilton Rating Scale for Depression. Subjective sleep disturbances were assessed using the Insomnia Severity Index (ISI). Detailed sleep pattern was acquired using sleep diary and actigraphy. Pain intensity was evaluated using a verbal rating scale, a visual analog scale, and a multidimensional pain scale.ResultsCross-sectional analyses found that insomnia symptoms and quantitative sleep parameters were related to pain symptoms. The correlations between sleep and pain scores were more significant after 3 months of pharmacotherapy as compared to baseline. After controlling for the severity of anxiety and depression, the ISI total score and actigraphy-derived wake after sleep onset and total sleep time remained significant in predicting pain.ConclusionThis study supports specific role of subjective sleep disturbances and actigraphic measures in predicting pain symptoms in major depressive disorder. Further studies using a micro-longitudinal design are necessary to find out the causal relationship between sleep and pain in depressed patients.     

Sleep parameters associated with long-term outcome following subthalamic deep brain stimulation in Parkinson's disease

IntroductionWe aimed to investigate the effects of changes in sleep architecture on long-term clinical outcome in patients with Parkinson's disease (PD) who underwent deep brain stimulation of subthalamic nuclei (STN DBS).MethodsWe followed up eight PD patients before and three years after STN DBS surgery. In addition to clinical assessments, polysomnography (PSG) followed by multiple sleep latency tests was performed before and after STN DBS, while stimulator was ON and OFF.ResultsSubjective sleep latency was significantly decreased (P = 0.033) and sleep duration was increased (P = 0.041), as measured by Pittsburgh sleep quality index. Latency to REM sleep stage was shortened after surgery with STN DBS ON (P = 0.002). Index of central type of abnormal respiratory events was significantly increased while stimulator was ON (P = 0.034). Total number of major body movements was found to be increased when stimulator was turned OFF (P = 0.012). Among PSG data obtained during STN DBS ON, it was observed that duration of N3 sleep was negatively correlated with UPDRS scores at 1st (P = 0.038) and 3rd (P = 0.045) post-operative years. Among PSG variables during STN DBS OFF, durations of N3 sleep (P = 0.017) and REM sleep (P = 0.041) were negatively correlated with UPDRS scores at post-operative 1st year.ConclusionDisturbances in sleep architecture are associated with higher UPDRS scores and worse prognosis at 1st and 3rd post-operative years. Similar results obtained while stimulator was OFF at the end of 1st year support the presence of microlesion effect after STN DBS, which is probably not long lasting.     

The sleep macroarchitecture of children at risk for depression recruited in sleep centers

ObjectiveThe primary aim of this study was to compare the sleep macroarchitecture of children and adolescents whose mothers have a history of depression with children and adolescents whose mothers do not.MethodPolysomnography (PSG) and Holter electroencephalogram (EEG) were used to compare the sleep architecture of 35 children whose mothers had at least one previous depressive episode (19 boys, aged 4–18 years, “high-risk” group) and 25 controls (13 males, aged 4–18 years, “low-risk” group) whose mothers had never had a depressive episode. The total sleep time, wakefulness after sleep onset (WASO), sleep latency, sleep efficiency, number of awakenings per hour of sleep, percentages of time spent in each sleep stage, rapid eye movement (REM) latency and the depressive symptoms of participants were measured.ResultsIn children (4–12 years old), the high-risk group exhibited significantly more depressive symptoms than controls (P = 0.02). However, PSG parameters were not significantly different between high-risk children and controls. In adolescents (13–18 years old), the high-risk subjects presented with significantly more depressive symptoms (P = 0.003), a significant increase in WASO (P = 0.019) and a significant decrease in sleep efficiency compared to controls (P = 0.009).ConclusionThis study shows that children and adolescents born from mothers with a history of at least one depressive episode had significantly more depressive symptoms than controls. However, only high-risk adolescents presented with concurrent alterations of sleep macroarchitecture.