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.     

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

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

Parasomnia as an occasion for the diagnosis of Parkinson's disease.

We report a case of Parkinson's disease (PD) diagnosed by REM sleep behavior disorder (RBD). The patient was a 68-year-old man. On admission, rigidity in the left upper and lower extremities, bradykinesia, and gait disturbance were noted. In addition, polysomnography revealed REM sleep without atonia (RWA), and a diagnosis of untreated PD associated with RBD was made. Polysomnographic data showed that REM density decreased and RWA tended to increase after administration of a combination of L-DOPA and DCI (L-DOPA/DCI). Thus, we considered that the pathophysiological mechanism of RBD in this case was based not only on the dysfunction of the brainstem mechanism of RWA, but also on the impairment of dopaminergic neuron.     

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.     

Rapid eye movement sleep behavior disorder and the link to alpha-synucleinopathies

Rapid eye movement (REM) sleep behavior disorder (RBD) involves REM sleep without atonia in conjunction with a recurrent nocturnal dream enactment behavior, with vocalizations such as shouting and screaming, and motor behaviors such as punching and kicking. Secondary RBD is well described in association with neurological disorders including Parkinson’s disease (PD), multiple system atrophy (MSA), and other conditions involving brainstem structures such as tumors. However, RBD alone is now considered to be a potential harbinger of later development of neurodegenerative disorders, in particular PD, MSA, dementia with Lewy bodies (DLB), and pure autonomic failure. These conditions are linked by their underpinning pathology of alpha-synuclein protein aggregation. In RBD, it is therefore important to recognize the potential risk for later development of an alpha-synucleinopathy, and to investigate for other potential causes such as medications. Other signs and symptoms have been described in RBD, such as orthostatic hypotension, or depression. While it is important to recognize these features to improve patient management, they may ultimately provide clinical clues that will lead to risk stratification for phenoconversion. A critical need is to improve our ability to counsel patients, particularly with regard to prognosis. The ability to identify who, of those with RBD, is at high risk for later neurodegenerative disorders will be paramount, and would in addition advance our understanding of the prodromal stages of the alpha-synucleinopathies. Moreover, recognition of at-risk individuals for neurodegenerative disorders may ultimately provide a platform for the testing of possible neuroprotective agents for these neurodegenerative disorders.     

Observations on muscle activity in REM sleep behavior disorder assessed with a semi-automated scoring algorithm

Objectives

Rapid eye movement (REM) sleep behavior disorder (RBD) is defined by dream enactment due to a failure of normal muscle atonia. Visual assessment of this muscle activity is time consuming and rater-dependent.

A case series and systematic review of rapid eye movement sleep behavior disorder outcome after deep brain stimulation in Parkinson's disease

REM-sleep behavior disorder (RBD) is a parasomnia and a common sleep disorder in Parkinson's disease (PD). While deep brain stimulation (DBS) is an established treatment for advanced PD with beneficial effects on cardinal PD motor symptoms, the data on the impact of DBS on RBD are limited and often controversial.We reviewed published articles that reported on RBD in the context of DBS surgery via systematic PubMed search. We identified 75 studies and included 12 studies, involving a total of 320 subjects, in our review. Results in respect to EMG activity outcome after subthalamic stimulation are inconsistent. We found no study that reported on RBD outcome after pallidal DBS and no DBS study quantified complex behavior during REM sleep.We also added data on RBD outcome after subthalamic (N = 4 patients) or pallidal (N = 3 patients) DBS from patients with PD with RBD, obtained as part of a prospective DBS study in our centre. Our case series showed an increase of complex behavior during REM (CB-REM) after surgery, independent of DBS target. Conversely, we found a trend towards increasing REM sleep without atonia (RSWA) in subthalamic-stimulated patients and a trend towards decreased RSWA in pallidal stimulated patients.We conclude that CB-REM and RSWA might represent two distinct elements in RBD and should be assessed separately, especially in studies that report on RBD outcome after treatment interventions. Further, larger, prospective, controlled studies in different DBS targets, reporting separately on the different RBD modalities, are needed.     

早期帕金森病患者快速眼动睡眠期行为障碍研究

目的探讨早期帕金森病患者快速眼动睡眠期行为障碍发生情况,以及帕金森病运动症状、非运动症状和快速眼动睡眠期行为障碍特点。方法共60例原发性帕金森病患者,采用统一帕金森病评价量表第二和第三部分(UPDRSⅡ和UPDRSⅢ)以及Hoehn-Yahr分期评价帕金森病非运动症状和运动症状,蒙特利尔认知评价量表评价认知功能,汉密尔顿焦虑量表和汉密尔顿抑郁量表评价焦虑和抑郁症状;中文版快速眼动睡眠期行为障碍筛查量表判断是否伴快速眼动睡眠期行为障碍,Epworth嗜睡量表(ESS)评价白天过度嗜睡程度;多导睡眠图监测睡眠障碍特征,包括下颌位相性肌电活动密度和快速眼动睡眠期肌肉失弛缓。结果 60例帕金森病患者中42例(70%)伴快速眼动睡眠期行为障碍(PD+RBD组),多导睡眠图监测其异常行为主要表现为上肢伸展抓握、肢体震颤抽搐、发笑、喊叫和怒骂等非暴力动作,仅2例出现暴力击打、蹬踢等异常行为。PD+RBD组患者年龄(P=0.024)、病程8年比例(P=0.000)、UPDRSⅡ(P=0.005)和UPDRSⅢ(P=0.001)评分、Hoehn-Yahr分期2级比例(P=0.007)、焦虑障碍(P=0.044)和抑郁障碍(P=0.001)比例,以及下颌位相性肌电活动密度(P=0.000)和快速眼动睡眠期肌肉失弛缓比例(P=0.000)均高于对照组,其中,PD+RBD组有16例(38.10%)快速眼动睡眠期行为障碍症状早于帕金森样症状5.20(3.91,6.51)年。结论年龄大、病程长、运动症状和非运动症状严重的帕金森病患者易伴发快速眼动睡眠期行为障碍,快速眼动睡眠期行为障碍可能是帕金森病的早期表现。多导睡眠图监测对早期帕金森病伴快速眼动睡眠期行为障碍的诊断有重要参考价值。     

Development of scales for assessment of rapid eye movement sleep behavior disorder (RBD)

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by an absence of normal skeletal muscle atonia during REM sleep and clinical features of disturbing dreams and dream enacting behaviors. Hence, the common sequelae are sleep-related injury and violence to both patients and bed-partners. Although polysomnographic evidence of REM sleep without atonia, is regarded as a gold standard for the confirmation of RBD diagnosis, polysomnography is both time and resource consuming. In order to facilitate early detection and clinical management, developing a convenient and suitable screening tool to identify individuals at risk of RBD would enable physicians to prioritize those who may require timely assessment and clinical intervention. In addition, the longitudinal course of RBD and its prognostic implication in predicting neurodegenerative disorders may suggest a potential therapeutic window for early preventive management of underlying progress of neurodegeneration. The availability of suitable RBD scales may facilitate timely assessment, accurate diagnosis and monitoring of disease progress of RBD. The present paper summarized recent research on the development of screening tools of RBD, their psychometric properties, and the applications of these questionnaires.     

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     

Olfactory deficit in idiopathic rapid eye movements sleep behavior disorder

INTRODUCTION: REM sleep behavior disorder (RBD) is a parasomnia characterized by a loss of atonia and an increased phasic muscle activity during REM sleep. Idiopathic RBD frequently herald an alpha-synucleinopathy, including such as Parkinson's disease (PD) and dementia with Lewy Body (DLB). Pathological changes in the anterior olfactory nucleus and olfactory loss occur very early in the course of PD and DLB. The aim of the study was to assess olfactory function in a large group of idiopathic RBD patients. METHODS: Fifty-four consecutive polysomnographically-confirmed iRBD patients (44 men, 10 women; mean age: 69.2+/-8.3 years; mean Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score: 4.9+/-4.3) and 54 age and gender-matched control subjects underwent the Brief University of Pennsylvania Smell Identification Test (B-SIT). RESULTS: A marked olfactory impairment was observed in the RBD group (mean B-SIT score: 7.1+/-2.5 versus 9.4+/-1.8; p < 0.0001), with 33 (61.1%) RBD patients versus 9 (16.6%) controls showing abnormal olfactory function (p < 0.0001). No correlation was found between the degree of olfactory loss and either duration of RBD symptoms or UPDRS-III score. Deficit in recognize paint thinner odorant showed the highest positive predictive value (0.95) for identifying idiopathic RBD. CONCLUSIONS: The olfactory deficit found in most idiopathic RBD patients shares similarities with that described in PD and may be a sign of a widespread neurodegenerative process. Its detection may help in identifying subjects at higher risk of developing an alpha-synucleinopathy-mediated neurodegeneration.     

Disturbance of rapid eye movement sleep in spinocerebellar ataxia type 2.

Five genetically confirmed spinocerebellar ataxia type 2 (SCA2) patients were admitted to our sleep laboratory for two all-night video-polysomnographies. A standard montage was used, including electroencephalography, vertical and horizontal electrooculography, electromyography of mental, submental, and tibialis anterior muscles, and respiratory monitoring. Four of five SCA2 patients had insufficient muscle atonia during rapid eye movement (REM) sleep. All patients exhibited myoclonic jerks during REM sleep, while elaborated behavior was not observed in the video. Abnormal motor control during sleep with periodic leg movements and REM sleep without atonia occurs frequently in SCA2. This finding may reflect a dysfunction of dopaminergic and/or brainstem and cerebellar outflow pathways.     

Comparison of the clinical features of rapid eye movement sleep behavior disorder in patients with Parkinson's disease and multiple system atrophy

Aims: The aim of this study was to evaluate differences in the clinical presentation and polysomnographic characteristics of rapid eye movement sleep behavior disorder (RBD) between patients with Parkinson's disease (PD) and those with multiple system atrophy (MSA). Methods: We conducted clinical interviews examining RBD symptoms, including violent and non‐violent behaviors, in 49 patients with PD and 16 patients with MSA (as well as their bed partners) and performed polysomnography on all subject patients. Results: Twenty‐seven patients with PD (55.1%) and 11 patients with MSA (68.8%) had rapid eye movement sleep without atonia (RWA) on polysomnogram. The relative amounts of RWA were quite similar between the two groups. For most of the RWA‐positive patients in both groups, RBD symptoms remained non‐violent or silent. RBD symptoms in PD patients seemed to increase with the course of PD, while most of the RBD symptoms in the MSA patients occurred just prior to or at the onset of MSA and then disappeared within a short period. Conclusion: Although PD and MSA frequently accompany RWA, RBD symptoms often remain non‐violent or silent. Differences in the course of RBD symptoms in patients with PD and MSA may reflect the difference in the degeneration process of the two disorders.     

Recent data on rapid eye movement sleep behavior disorder in patients with Parkinson disease: analysis of behaviors,movements, and periodic limb movements

Rapid eye movement (REM) sleep behavior disorder (RBD) is a fascinating parasomnia in which patients are able to enact their dreams because of a lack of muscle atonia during REM sleep. RBD represents a unique window into the dream world. Frequently associated with Parkinson’s disease (PD), RBD raises various issues about dream modifications in this pathology and about aggressiveness during RBD episodes in placid patients during wakefulness. Studies on these behaviors have underlined their non-stereotyped, action-filled and violent characteristics but also their isomorphism with dream content. Complex, learnt behaviors may reflect the cortical involvement in this parasomnia but the more frequent elementary movements and the associated periodic limb movements during sleep also implicate the brainstem. Surprisingly, patients with PD have an improvement of their movements during their RBD as if they were disease-free. Also not yet understood, this improvement of movement during REM sleep raises issues about the pathways involved in RBD and about the possibility of using this pathway to improve movement in PD during the day.     

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.     

Phenomenology of dreams in Parkinson's disease.

Rapid eye movement sleep behavior disorder (RBD) occurs in approximately one third of patients with Parkinson's disease (PD) and is associated with a loss of muscle atonia during REM sleep and aggressive dream content. We examined the dream characteristics of PD patients to determine whether dream content differed between patients with RBD and without RBD, men and women with RBD, and men and women with PD. One hundred-twenty patients with a diagnosis of idiopathic PD were consecutively recruited from a movement disorders clinic and were assessed for RBD using clinical diagnostic criteria of the International Classification of Sleep Disorders Revised (2001). Verbatim dream content was obtained from each patient and categorized into dream themes that were coded into nominal categories. Fisher's exact tests determined whether particular dreams were correlated with RBD versus non-RBD, men and women with RBD, and men and women with PD. RBD patients had a higher percentage of violent dreams compared to non-RBD patients. There were no significant sex differences in the dream content of RBD patients. Men with PD had more aggressive dreams compared to females with PD. Aggressive dream content was characteristic of RBD patients and sex differences exist in the dream content of the PD population.     

Perspectives on the rapid eye movement sleep switch in rapid eye movement sleep behavior disorder

Rapid eye movement (REM) sleep in mammals is associated with wakelike cortical and hippocampal activation and concurrent postural muscle atonia. Research during the past 5 decades has revealed the details of the neural circuitry regulating REM sleep and muscle atonia during this state. REM-active glutamatergic neurons in the sublaterodorsal nucleus (SLD) of the dorsal pons are critical for generation for REM sleep atonia. Descending projections from SLD glutamatergic neurons activate inhibitory premotor neurons in the ventromedial medulla (VMM) and in the spinal cord to antagonize the glutamatergic supraspinal inputs on the motor neurons during REM sleep. REM sleep behavior disorder (RBD) consists of simple behaviors (i.e., twitching, jerking) and complex behaviors (i.e., defensive behavior, talking). Animal research has lead to the hypothesis that complex behaviors in RBD are due to SLD pathology, while simple behaviors of RBD may be due to less severe SLD pathology or dysfunction of the VMM, ventral pons, or spinal cord.     

Quantitative assessment of isolated rapid eye movement (REM) sleep without atonia without clinical REM sleep behavior disorder: clinical and research implications

BackgroundRapid eye movement (REM) sleep without atonia (RWA) is observed in some patients without a clinical history of REM sleep behavior disorder (RBD). It remains unknown whether these patients meet the refined quantitative electromyographic (EMG) criteria supporting a clinical RBD diagnosis. We quantitatively evaluated EMG activity and investigated its overnight distribution in patients with isolated qualitative RWA.MethodsFifty participants with an incidental polysomnographic finding of RWA (isolated qualitative RWA) were included. Tonic, phasic, and ‘any’ EMG activity during REM sleep on PSG were quantified retrospectively.ResultsReferring to the quantitative cut-off values for a polysomnographic diagnosis of RBD, 7/50 (14%) and 6/50 (12%) of the patients showed phasic and ‘any’ EMG activity in the mentalis muscle above the respective cut-off values. No patient was above the cut-off value for tonic EMG activity or phasic EMG activity in the anterior tibialis muscles. Patients with RWA above the cut-off value showed higher amounts of RWA during later REM sleep periods.ConclusionsThis is the first study showing that some subjects with incidental RWA meet the refined quantitative EMG criteria for a diagnosis of RBD. Future longitudinal studies must investigate whether this subgroup with isolated qualitative RWA is at an increased risk of developing fully expressed RBD and/or neurodegenerative disease.     

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.     

快速眼动期睡眠行为障碍与突触核蛋白病的关系

目的 研究快速眼动(REM)期睡眠行为障碍(RBD)在突触核蛋白病中的出现率、出现时间、电生理特点,探讨RBD与突触核蛋白病之间的关系以及电生理诊断指标.方法 通过对患者的睡眠状况调查以及夜间多导睡眠监测(NPSG),研究本组疾病的睡眠障碍特征:(1)主观睡眠调查:帕金森病(PD)患者66例,多系统萎缩(MSA)患者30例,性别、年龄匹配的健康对照组65名,询问睡眠史,了解RBD出现的比例及出现时间.(2)NPSG:PD组8例、MSA组13例,健康对照组15名,所有受试者行连续两夜NPSG监测.分析伴发RBD的突触核蛋白病患者的NPSG特点.结果 PD和MSA合并RBD比例分别是59.1%(39/66)和86.6%(26/30),明显高于对照组(4.6%,3/65),其中RBD早于两种变性病临床发病的患者比例分别是46.2%(18/39)和84.6%(22/26).PD和MSA合并RBD最主要的NPSG特点是:REM期肌肉弛缓现象消失(RWA)和运动增多.RWA比例和位相性肌电活动密度可能成为神经变性病合并RBD的NPSG诊断指标.结论 RBD在PD和MSA患者中出现率明显增高,部分RBD发生先于变性病,提示RBD与突触核蛋白病关系密切,RBD有可能是突触核蛋白病的早期表现.NPSG特征应作为RBD的主要诊断标准,RWA比例和位相性肌电活动密度可能成为神经变性病合并RBD的NPSG诊断指标.