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.     

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.     

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.     

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.     

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.     

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.     

Rapid eye movement sleep behaviour disorder in women with Parkinson’s disease is an underdiagnosed entity

Rapid eye movement sleep behavior disorder (RBD) is common in Parkinson’s disease (PD). Little information exists about RBD in women with PD. The aim of this study was to determine the clinical expression of RBD in women with PD and note any differences in women with PD with and without RBD. One hundred fifty-six patients with PD were recruited. There were 37 women with PD and probable RBD was diagnosed using the RBD Screening Questionnaire. Other scales included Pittsburgh Sleep Quality Index, Parkinson’s Disease Sleep Scale, Epworth Sleep Scale, Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. Probable RBD was diagnosed in 10 women with PD (27%). Most often (70%) RBD occurred after the onset of parkinsonian symptoms. Women with probable RBD were older, had shorter duration of PD symptoms, lower tremor score, and higher axial signs score. They had insomnia (80% versus non-probable RBD patients 44%, p = 0.019), and poor sleep quality with excessive daytime sleepiness. Anxiety and depression were common in women with probable RBD. Episodes were brief and confined to vocalization and simple limb movements. No injury to self or bed partners was noted. Women with PD have fewer fights and less aggressive dream enacting behaviour than men, but suffer from significant disturbed sleep, and levels of anxiety and depression.     

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 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.     

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.     

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.     

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.     

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.     

Is obstructive sleep apnea a problem in Parkinson’s disease?

BackgroundParkinson’s disease (PD) is associated with sleep disorders and daytime sleepiness. Upper airway dysfunction in PD may promote obstructive sleep apnea. However, the frequency and clinical relevance of sleep-disordered breathing in PD remains unclear.MethodsSleep apnea symptoms, cardiovascular events and treatment were collected in 100 patients with PD (50 unselected, consecutive patients matched for age, sex and body mass index with 50 patients referred for sleepiness) and 50 in-hospital controls. The motor and cognitive status was evaluated in patients with PD. The 150 subjects underwent a video-polysomnography.ResultsSleep apnea (defined as an apnea–hypopnea index greater than 5) was less frequent in the PD group (27% patients, including 6% with mild, 11% with moderate and 10% with severe sleep apnea) than in the control group (40% in-hospital controls, p < 0.002). Sleep apnea was not associated with increased sleepiness, nocturia, depression, cognitive impairment and cardiovascular events in patients with PD. Sleep apnea was more frequent and severe in the most disabled patients. Patients with PD did not display sleep hypoventilation, stridor and abnormal central sleep apnea. In patients with REM sleep behavior disorders, snoring and obstructive sleep apnea occurred during REM sleep, although the chin muscle tone was maintained.ConclusionObstructive sleep apnea does not seem to be a clinically relevant issue in PD. Daytime sleepiness, nocturia and cognitive impairment are mostly caused by other, non-apneic mechanisms. The maintenance of chin muscle tone during REM sleep behavior disorder has no influence on the frequency of apneic events.     

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.     

Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder

ObjectiveTo determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder.MethodsThe clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria.Results172 cases were identified, of whom 143 (83%) were men. The mean ± SD age of onset in years for the core features were as follows – RBD, 62 ± 14 (range, 20–93), cognitive impairment (n = 147); 69 ± 10 (range, 22–90), parkinsonism (n = 151); 68 ± 9 (range, 20–92), and autonomic dysfunction (n = 42); 62 ± 12 (range, 23–81). Death age was 75 ± 9 years (range, 24–96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10 ± 12 (range, 1–61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n = 97), Parkinson’s disease with or without mild cognitive impairment or dementia (n = 32), multiple system atrophy (MSA) (n = 19), Alzheimer’s disease (AD)(n = 9) and other various disorders including secondary narcolepsy (n = 2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n = 1). The neuropathologic diagnoses were Lewy body disease (LBD)(n = 77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n = 59), MSA (n = 19), AD (n = 6), progressive supranulear palsy (PSP) (n = 2), other mixed neurodegenerative pathologies (n = 6), NBIA-1/LBD/tauopathy (n = 1), and hypothalamic structural lesions (n = 2). Among the neurodegenerative disorders associated with RBD (n = 170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features.ConclusionsIn this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.     

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.     

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.