Rapid Eye Movement Sleep Behavior Disorder

Abstract: Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by loss of normal voluntary muscle atonia during REM sleep, and is associated with excessive motor activity related to dreaming. The movements are often potentially harmful and may lead to repeated injuries to the patients and/or their bedpartners.
RBD is more common in the elderly and affects predominantly males. A recent survey reported an estimated prevalence of RBD of 0.38% in the elderly and 0.5% in the general population. Because the treatment of RBD is effective and safe in most cases, awareness and diagnosis of RBD is critical. Overnight polysomnography is required to differentiate accurately between RBD and other sleep disorders, even though the patients have been clinically diagnosed as RBD according to the minimal criteria of the International Classification of Sleep Disorders. Muscle tone persists during REM sleep in RBD patients, and may be frequently augmented for prolonged periods of time. The density of REMs or phasic muscle activity occurring during REM sleep significantly increases in these patients, although their overall sleep architecture is usually normal, with the expected cycles of non-REM and REM sleep.
RBD occurs in both acute and chronic form. Acute cases are associated with intoxication and withdrawal. Chronic cases are most often either idiopathic or associated with neurological disorders—especially neurodegenerative diseases. The etiology of idiopathic RBD is still unknown, but a recent study has shown an association between some cases of idiopathic RBD and neurodegenerative disorders with parkinsonism such as Parkinson's disease, multiple system atrophy, and diffuse Lewy body disease. RBD patients thus need to be carefully followed up in terms of neurological evaluation.     

Ethical Considerations in Screening for Rapid Eye Movement Sleep Behavior Disorder in the General Population

Clinical studies have shown that up to 90% of patients with idiopathic rapid eye movement sleep behavior disorder (RBD) will eventually be diagnosed with a clinical α-synucleinopathy. Because of this high conversion rate, screening for RBD is often performed to identify eligible participants for studies aimed at elucidating the prodromal phase of α-synucleinopathies. However, screening for RBD, especially in the general population, raises many ethical dilemmas. In light of the existing ethical literature and our experience in establishing a screening approach for RBD in the Rotterdam Study, we discuss ethical dilemmas when screening for RBD in population-based studies. We conclude that informing study participants about the reason for invitation and the possible trajectory that lies ahead when participating is essential. However, participants should not be troubled unnecessarily by giving them detailed information about possible diagnoses or associated disease risks. © 2020 International Parkinson and Movement Disorder Society     

The Views of Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder on Risk Disclosure

Background

Isolated rapid eye movement sleep behavior disorder (iRBD) is associated with an increased risk of Parkinson's disease and other synucleinopathies. There is no consensus about disclosure of this risk to patients with iRBD.

Objective

The objective of our study was to assess the experiences of risk disclosure in a group of patients with iRBD and their views on what, when, and how this should be done.

Methods

A survey was administered to patients with iRBD to explore their experiences and views on risk disclosure.

Results

Thirty-one patients with iRBD (28 males; mean age, 70 [SD 8.7] years; mean disease duration, 8.7 [SD 6.4] years) were included. A third reported they had not been informed about the link between iRBD and other conditions by clinicians at diagnosis, but 90% would have liked to have received prognostic information, and 60% indicated that this should happen at the point that iRBD was diagnosed. Most participants wanted this information to come from the clinician diagnosing and treating iRBD (90.3%). Almost three-quarters (72.2%) had searched for this information online.

Conclusions

Patients with iRBD mostly wished to have received information regarding the potential implications of iRBD when the diagnosis was made. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Correlations of Some Physical Variables with REM Sleep and Slow Wave Sleep in Man

Polysomnography recordings were taken on 11 healthy male students aged 19–23 years. The correlations were examined between the various physical variables and the appearance rates of REM sleep and slow wave sleep (SWS). The height showed a significant inverse correlation with %st.4 sleep and with %SWS and the plantar length with %SWS. The body weight and chest circumference showed a significant inverse correlation with %REM sleep. The weight/height ratio tended toward an inverse correlation with %REM sleep. Both the body surface area and basal metabolic rate showed a significant inverse correlation with %st.4 and %REM sleep. There was no significant correlation between the total sleep time and each physical variable. From these results the roles of REM sleep and slow wave sleep in man were discussed.     

快眼动睡眠调控机制及快眼动睡眠期行为障碍的神经通路相关研究

快眼动(REM)睡眠行为障碍(RBD)是一种以REM睡眠期骨骼肌弛缓能力障碍为特征的异态睡眠。患病个体因此在REM睡眠期出现不同严重程度的与梦境吻合的异常行为。至今与RBD相关的神经核团及通路尚未完全阐明,存在不同假说。文中从REM睡眠神经调控机制入手,结合猫和大鼠RBD模型发现,回顾近年来RBD相关神经通路研究的进展,并与人类RBD病例对照,综合阐述RBD产生的相关神经通路,为RBD发病机制的研究进一步提供线索。     

Study on the Effects of L-5HTP on the Stages of Sleep in Man as Evaluated by Using Sleep Deprivation

Abstract: The effects of L-5HTP 200 mg on the EEG sleep pattern were investigated in normal subjects. When L-5HTP 200 mg was orally administered, only %S1 significantly decreased in comparison with the baseline. There was no change in any sleep stage on the first recovery night. On the second recovery night, %S1 significantly decreased, while %SR increased significantly. SWS did not show any change. The effects of L-5HTP 200 mg were investigated on the first recovery night after one night of sleep deprivation. SWS significantly increased on the first recovery night when a placebo was given, while this rebound increase of SWS disappeared and %S2 significantly increased on the first recovery night when L-5HTP was given. %SR significantly increased on the next night after the L-5HTP night.     

Positron Emission Tomography Correlates of Visually-Scored Electroencephalographic Waveforms During Non-Rapid Eye Movement Sleep

Visually-scored, non-Rapid Eye Movement (REM) sleep electroencephalographic (EEG) waveform activity for each 30-s sleep scored epoch—including the number of sleep spindles, the number of K-complexes, and the percentage of delta waves occupying the epoch—was correlated with H₂¹⁵O positron emission tomography. Sleep spindle correlations included positive correlations in the thalamus and right hippocampus. K-complex correlations included positive correlations in the frontomedian prefrontal cortex and cerebellum. Delta wave correlations included negative correlations in the thalamus, frontomedian prefrontal cortex, dorsal pons, and primary visual cortex. Each pattern of correlations may suggest a functional significance for these waveforms that relates to a waking outcome.     

特发性快眼动睡眠期行为障碍患者大脑相关皮质厚度的影像形态学变化

目的探讨特发性快眼动睡眠期行为障碍(iRBD)患者大脑相关皮质的形态学变化,为研究iRBD的中枢机制提供客观依据。方法对20例多导睡眠监测(PSG)确诊的iRBD患者(iRBD组)和20名年龄匹配的健康对照者(对照组)进行MR3D T1W1扫描。在Matlab平台上应用SPM12软件和CAT12工具箱进行影像数据处理和统计学分析,处理过程包括脑的空间标准化、灰白质分割、自动化重建脑表面及空间平滑,采用基于脑表面的形态测定法对iRBD组和对照组双侧脑皮质厚度进行统计学分析比较。结果与对照组比较,iRBD组左侧额下回、额中回、扣带回皮质厚度显著变薄;右侧大脑半球未见皮质厚度明显变薄的脑区;双侧大脑半球未见皮质厚度明显增加的脑区。结论 MR3D T1W1扫描发现i RBD患者存在相关脑区皮质厚度变薄,为其脑代谢及血流灌注异常提供影像解剖学基础。     

Glutamatergic Neurons in the Preoptic Hypothalamus Promote Wakefulness,Destabilize NREM Sleep,Suppress REM Sleep,and Regulate Cortical Dynamics

Clinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study, we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2⁺) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. We also demonstrate, for the first time, that activation of these preoptic glutamatergic neurons causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, decreases body temperature, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons can initiate, but not maintain, arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the hypothesis that the preoptic area causally contributes to the regulation of both sleep and wakefulness.SIGNIFICANCE STATEMENT Historically, the preoptic area of the hypothalamus has been considered a key site for sleep generation. However, emerging modeling and empirical data suggest that this region might play a dual role in sleep-wake control. We demonstrate that chemogenetic stimulation of preoptic glutamatergic neurons produces brief arousals that fragment sleep, persistently suppresses REM sleep, causes hypothermia, and shifts EEG patterns toward a “lighter” NREM sleep state. We propose that preoptic glutamatergic neurons can initiate, but not maintain, arousal from sleep and gate REM sleep generation, possibly to block REM-like intrusions during NREM-to-wake transitions. In contrast to the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic, we provide further evidence that preoptic neurons also generate wakefulness.     

Cholinergic Nucleus 4 Degeneration and Cognitive Impairment in Isolated Rapid Eye Movement Sleep Behavior Disorder

Background

Cholinergic nucleus 4 (Ch4) degeneration is associated with cognitive impairment in Parkinson's disease and dementia with Lewy bodies, but it is unknown if Ch4 degeneration is also present in isolated rapid eye movement sleep behavior disorder (iRBD).

Objective

The aim was to determine if there is evidence of Ch4 degeneration in patients with iRBD and if it is associated with cognitive impairment.

Methods

We analyzed the clinical and neuropsychological data of 35 iRBD patients and 35 age- and sex-matched healthy controls. Regional gray matter density (GMD) was calculated for Ch4 using probabilistic maps applied to brain magnetic resonance imaging (MRI).

Results

Ch4 GMD was significantly lower in the iRBD group compared to controls (0.417 vs. 0.441, P = 0.02). Ch4 GMD was also found to be a significant predictor of letter number sequencing (β-coefficient = 58.31, P = 0.026, 95% confidence interval [7.47, 109.15]), a measure of working memory.

Conclusions

iRBD is associated with Ch4 degeneration, and Ch4 degeneration in iRBD is associated with impairment in working memory. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.