Investigating rapid eye movement sleep without atonia in Parkinson's disease using the rapid eye movement sleep behavior disorder screening questionnaire

Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently observed in patients with Parkinson's disease (PD). Accurate diagnosis is essential for managing this condition. Furthermore, the emergence of idiopathic RBD in later life can represent a premotor feature, heralding the development of PD. Reliable, accurate methods for identifying RBD may offer a window for early intervention. This study sought to identify whether the RBD screening questionnaire (RBDSQ) and three questionnaires focused on dream enactment were able to correctly identify patients with REM without atonia (RWA), the neurophysiological hallmark of RBD. Forty‐six patients with PD underwent neurological and sleep assessment in addition to completing the RBDSQ, the RBD single question (RBD1Q), and the Mayo Sleep Questionnaire (MSQ). The REM atonia index was derived for all participants as an objective measure of RWA. Patients identified to be RBD positive on the RBDSQ did not show increased RWA on polysomnography (80% sensitivity and 55% specificity). However, patients positive for RBD on questionnaires specific to dream enactment correctly identified higher degrees of RWA and improved the diagnostic accuracy of these questionnaires. This study suggests that the RBDSQ does not accurately identify RWA, essential for diagnosing RBD in PD. Furthermore, the results suggest that self‐report measures of RBD need to focus questions on dream enactment behavior to better identify RWA and RBD. Further studies are needed to develop accurate determination and quantification of RWA in RBD to improve management of patients with PD in the future. © 2014 International Parkinson and Movement Disorder Society     

Decreased phasic EMG activity during rapid eye movement sleep in treatment‐naïve Parkinson's disease: Effects of treatment with levodopa and progression of illness

Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently associated with Parkinson's disease (PD) and may anticipate its diagnosis by several years. We assessed the presence of motor dyscontrol during REM sleep in treatment‐naïve PD patients and investigated the putative effect of levodopa (L ‐dopa) treatment on motor activity. Overnight sleep studies were performed on 15 previously untreated PD patients and 14 controls at baseline, again after a 3‐ to 9‐month treatment period with a low dose of L ‐dopa, and 2 to 5 days after treatment discontinuation (in 8 patients). No differences in sleep parameters were observed across groups or treatment conditions. None of the patients met criteria for RBD at baseline, whereas 5 patients were symptomatic at the time of the second sleep study. A quantitative analysis of electromyographic (EMG) activity during REM sleep showed a lower phasic twitching activity in untreated PD than in controls. However, an increase in both phasic twitching and tonic activity was found after treatment with L ‐dopa. Discontinuation of treatment resulted in a return to pretreatment values of phasic but not of tonic EMG activity. Thus, the increase in phasic activity seems to depend on the effects of L ‐dopa, whereas the increase in tonic EMG activity during REM sleep might be caused by other factors such as the progression of disease. Potential implications for the understanding of the relationship between RBD and PD are discussed. © 2002 Movement Disorder Society     

Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder

Background: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear. Objective: To study the role of MAPT variants in rapid eye movement sleep behavior disorder. Methods: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950). MAPT‐associated variants and the entire coding sequence of MAPT were analyzed. Age‐, sex‐, and ethnicity‐adjusted analyses were performed to examine the association between MAPT, PD, and rapid eye movement sleep behavior disorder. Results: MAPT‐H2 variants were associated with PD (odds ratios: 0.62‐0.65; P = 0.010‐0.019), but not with rapid eye movement sleep behavior disorder. In PD, the H1 haplotype odds ratio was 1.60 (95% confidence interval: 1.12‐2.28; P = 0.009), and the H2 odds ratio was 0.68 (95% confidence interval: 0.48‐0.96; P = 0.03). The H2/H1 haplotypes were not associated with rapid eye movement sleep behavior disorder. Conclusions: Our results confirm the protective effect of the MAPT‐H2 haplotype in PD, and define its components. Furthermore, our results suggest that MAPT does not play a major role in rapid eye movement sleep behavior disorder, emphasizing different genetic background than in PD in this locus. © 2018 International Parkinson and Movement Disorder Society     

Visual hallucinations as REM sleep behavior disorders in patients with Parkinson's disease.

To clarify whether visual hallucinations in patients with Parkinson's disease (PD) are related to rapid eye movement (REM) sleep, nocturnal polysomnographic variables were compared between a group with hallucinations (hallucinators, n = 14) and a group without hallucinations (nonhallucinators, n = 8). A multiple sleep latency test (MSLT) was performed on 3 hallucinators, and the content of dreams during daytime REM sleep was investigated. The efficacy of clonazepam, a standard treatment choice for REM sleep behavior disorders, was investigated in 8 hallucinators. Nocturnal polysomnograms of the hallucinators showed a higher amount of stage 1-REM sleep with tonic electromyogram (stage 1-REM) than the nonhallucinators, and the reported occurrences of nocturnal hallucinations corresponded with the periods of stage REM or stage 1-REM in most hallucinators. The frequency of sleep onset REM periods (SOREMP) on the MSLT were pathologically high in the hallucinators, and the content of the dreams during the MSLT period was quite similar to their hallucinations. During clonazepam treatment, the frequency of hallucinatory symptoms decreased in 5 of 8 hallucinators. These results indicate that visual hallucinations in PD are likely to be related to a REM sleep disorder manifested as the appearance of both stage 1-REM during the night and SOREMP in the daytime.     

Clinical and dopaminergic imaging characteristics of the FARPRESTO cohort of trial-ready idiopathic rapid eye movement sleep behavior patients

Introduction

Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the ideal target for disease-modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well-characterized subjects.

Methods

Polysomnography-confirmed iRBD patients were retrospectively and prospectively enrolled. Baseline harmonized clinical and nigrostriatal functioning data were collected at baseline. Nigrostriatal functioning was evaluated by dopamine transporter-single-photon emission computed tomography (DaT-SPECT) and categorized with visual semi-quantification. Longitudinal data were evaluated to assess phenoconversion. Cox regressions were applied to calculate hazard ratios.

Results

365 patients were enrolled, and 289 patients with follow-up (age 67.7 ± 7.3 years, 237 males, mean follow-up 40 ± 37 months) were included in this study. At follow-up, 97 iRBD patients (33.6%) phenoconverted to an overt synucleinopathy. Older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression, and visual semi-quantification of nigrostriatal functioning predicted phenoconversion. The remaining 268 patients are in follow-up within the FARPRESTO project.

Conclusions

Clinical data (older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression) predicted phenoconversion in this multicenter, longitudinal, observational study. A standardized visual approach for semi-quantification of DaT-SPECT is proposed as a practical risk factor for phenoconversion in iRBD patients. Of note, non-converted and newly diagnosed iRBD patients, who represent a trial-ready cohort for upcoming disease-modification trials, are currently being enrolled and followed in the FARPRESTO study. New data are expected to allow better risk characterization.     

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

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

伴与不伴快速眼动睡眠行为障碍帕金森病患者临床差异的meta分析

目的系统评价伴与不伴快速眼动睡眠行为障碍(RBD)帕金森病(PD)患者之间临床特征的差异。方法检索Pub Med、EMbase等外文数据库及中国生物医学数据库(CMB)、中国知识基础设施工程(CNKI)、维普中文科技期刊全文数据库(VIP)、万方数据库等中文数据库关于PD与RBD相关性分析的病例对照研究,检索时限从建库至2018年09月01日。对入选文献进行质量评价,并用Stata 12. 0软件进行Meta分析。结果共纳入了17项符合标准的病例对照研究,共计PD患者3006例,Meta分析结果显示:与不伴RBD的PD患者相比,伴RBD的PD患者年龄更大(SMD=0. 26; 95%CI0. 19～0. 34; P 0. 00 001)、病程更长(SMD=0. 29; 95%CI 0. 21～0. 37; P 0. 00 001)、Hoehn-Yahr分级更高(SMD=0. 22; 95%CI 0. 11～0. 33; P 0. 00 001)、UPDRS-III评分更高(SMD=0. 25; 95%CI 0. 15～0. 36; P 0. 00 001)、左旋多巴剂量更大(SMD=0. 17; 95%CI 0. 08～0. 26; P 0. 00 001),更易出现症状波动(OR=1. 65; 95%CI1. 34～2. 03; P0. 00 001)、异动症(OR=2. 24; 95%CI 1. 74～2. 88; P 0. 00 001),MMSE评分更低(SMD=-0. 23; 95%CI-0. 40～-0. 06; P=0. 008),幻觉(OR=3. 15; 95%CI 2. 06～4. 80; P 0. 00 001)更多见,而性别(OR=1. 15; 95%CI 0. 99～1. 35; P=0. 07)、发病年龄(SMD=0. 09; 95%CI-0. 01～0. 19; P=0. 08)组间差异不明显。结论 PD患者中RBD的发生与患者年龄、病程有关,且伴RBD的PD患者需要更高的左旋多巴剂量、更易出现运动并发症,非运动症状更明显,提示伴RBD的PD患者中枢神经系统变性程度更严重、损害范围更广泛。     

Impulse control disorder and rapid eye movement sleep behavior disorder in Parkinson's disease

IntroductionThe relationship between ICD and RBD is still not yet understood and the results from the current literature are contradictory in PD. We aimed to explore the association between rapid eye movement (REM) sleep behavior disorder (RBD) and impulse control disorder in Parkinson's disease.MethodsNinety-eight non-demented patients with Parkinson's disease underwent one night of video-polysomnography recording. The diagnosis of RBD was established according to clinical and polysomnographic criteria. Impulse control disorders were determined by a gold standard, semi-structured diagnostic interview.ResultsHalf of the patients (n = 49) reported clinical history of RBD while polysomnographic diagnosis of RBD was confirmed in 31.6% of the patients (n = 31). At least one impulse control disorder was identified in 21.4% of patients, 22.6% with RBD and 20.9% without. Logistic regression controlling for potential confounders indicated that both clinical RBD (OR = 0.34, 95% CI = 0.07–1.48, P = 0.15) and polysomnographic confirmed RBD diagnoses (OR = 0.1.28, 95% CI = 0.31–5.33, P = 0.34) were not associated with impulse control disorder.ConclusionIn Parkinson's disease, REM Sleep Behavior Disorder is not associated with impulse control disorder. The results of our study do not support the notion that PSG-confirmed RBD and ICD share a common pathophysiology.     

SCOPA‐sleep and PDSS: Two scales for assessment of sleep disorder in Parkinson's disease

This study evaluated the comparative validity and usefulness of the Parkinson's Disease Sleep Scale (PDSS) and the Scales for Outcomes in PD‐Sleep Scale (SCOPA‐S), two disease‐specific rating scales for assessing sleep disorders in Parkinson's disease (PD). Hoehn and Yahr staging (HY), SCOPA‐Motor, Mini‐Mental State Examination, Clinical Impression of Severity Index for PD, Hospital Anxiety and Depression Scale, EuroQoL, and SCOPA‐Psychosocial, in addition to PDSS and SCOPA‐S (night‐time sleep (NS) and daytime sleepiness (DS) subscales), were applied to 187 consecutive PD patients. PDSS and SCOPA‐S proved similar in acceptability, scaling assumptions, precision, and internal consistency (Cronbach's α = 0.82–0.84). Factor analysis revealed five separate factors for PDSS (67% of the variance) and one factor for each SCOPA‐S subscale (60% of the variance for NS and 57% for DS). Correlation coefficient between PDSS and SCOPA‐S NS was ?0.60. Sleep scales correlated moderately with mood, low‐to‐moderate with HRQoL, and low with the rest of measures. PDSS and SCOPA‐S DS discriminated between patients grouped by HY severity levels and disease duration. Cutoff points of 82/83 for PDSS and 6/7 for SCOPA‐S NS were drawn to identify PD patients with sleep problems. Depression/anxiety scores explained 26% for PDSS and 22% for SCOPA‐S NS scores. Both scales provide valid, reliable, and useful means to evaluate sleep disorders in PD. PDSS may be used to obtain a profile about potential causes of “bad sleep,” but is barely useful to assess DS, whereas SCOPA‐S assesses nocturnal sleep disorders and daytime somnolence at a similar extent, without exploring the potential causes. © 2008 Movement Disorder Society     

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

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

Testosterone not associated with violent dreams or REM sleep behavior disorder in men with Parkinson's.

We examined the relationship between testosterone levels, violent dreams, and REM sleep behavior disorder (RBD) in 31 men with Parkinson's disease (PD): 12 with clinical RBD and 19 without. All PD patients with clinical RBD experienced violent dreams, but none of the 19 non-RBD patients reported violent dreams. While dream content appears to be more aggressive in PD patients with clinical RBD, the presence of violent dreams or clinical RBD is not associated with testosterone levels in men with PD.