Chapter 53 - REM sleep parasomnias

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dreamenacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with Parkinsonian disorders, but is also reported in narcolepsy. Most patients with narcolepsy with cataplexy lack the hypocretin neurons in the lateral hypothalamus. In contrast, RBD, RSWA, and hypocretin deficiency are rare in narcolepsy without cataplexy. Phasic motor activity in REM and non-REM (NREM) and dreamenacting behavior (RBD) coexist with cataplexy in narcolepsy because of hypocretin deficiency. Thus, hypocretin deficiency is linked to the two major disturbances of REM sleep motor regulation in narcolepsy: RBD and cataplexy. Moreover, it is likely that hypocretin deficiency independently predicts periodic limb movements in REM and NREM sleep, probably via involvement of the dopaminergic system. This supports the hypothesis that an impaired hypocretin system causes general instability of motor regulation during wakefulness, REM and NREM sleep in human narcolepsy. We propose that hypocretin neurons are centrally involved in motor tone control during wakefulness and sleep in humans and that hypocretin deficiency causes a functional defect in the motor control involved in the development of cataplexy during wakefulness and RBD/RSWA/ phasic motor activity during REM sleep.

Rapid eye movement (REM) sleep behaviour disorder is a REM sleep parasomnia characterised by the loss of the physiological muscle atonia during REM sleep, resulting in dream enactment behaviours that may cause injuries to patients or their bed partners. The nocturnal motor episodes seem to respond to the dream contents, which are often vivid and violent. These behavioural and oneiric features make the REM sleep behaviour disorder a potential model to study dreams. This review aims to unify the literature about dream recall in REM sleep behaviour disorder as a privileged approach to study dreams, systematically reviewing studies that applied retrospective and prospective experimental designs to provide a comprehensive overview of qualitative and quantitative aspects of dream recall in this REM sleep parasomnia. The present work highlights that the study of dreaming in REM sleep behaviour disorder is useful to understand unique aspects of this pathology and to explore neurobiological, electrophysiological, and cognitive mechanisms of REM sleep and dreaming.

Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy. Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without cataplexy. Main outcome measures were: rapid eye movement sleep behaviour disorder symptoms; short and long muscle activations per hour rapid eye movement and non-rapid eye movement sleep; and periodic and non-periodic limb movements per hour rapid eye movement and non-rapid eye movement sleep. Outcome variables were analysed in relation to cataplexy and hypocretin deficiency with uni- and multivariate logistic/linear regression models, controlling for possible rapid eye movement sleep behaviour disorder biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Only hypocretin deficiency independently predicted rapid eye movement sleep behaviour disorder symptoms (relative risk = 3.69, P = 0.03), long muscle activations per hour rapid eye movement sleep (ln-coefficient = 0.81, P < 0.01), and short muscle activations per hour rapid eye movement sleep (ln-coefficient = 1.01, P < 0.01). Likewise, periodic limb movements per hour rapid eye movement and non-rapid eye movement sleep were only associated with hypocretin deficiency (P < 0.01). A significant association between hypocretin deficiency and cataplexy was confirmed (P < 0.01). In a sub-analysis, hypocretin deficiency suggested the association of periodic limb movements and rapid eye movement sleep behaviour disorder outcomes (symptoms, non-periodic short and long muscle activity) in rapid eye movement sleep. Our results support the hypothesis that hypocretin deficiency is independently associated with rapid eye movement sleep behaviour disorder in narcolepsy. Thus, hypocretin deficiency is linked to the two major disturbances of rapid eye movement sleep motor regulation in narcolepsy: rapid eye movement sleep behaviour disorder and cataplexy. Hypocretin deficiency is also significantly associated with periodic limb movements in rapid eye movement and non-rapid eye movement sleep, and provides a possible pathophysiological link between rapid eye movement sleep behaviour disorder and periodic limb movements in narcolepsy. The study supports the hypothesis that an impaired hypocretin system causes a general instability of motor regulation during wakefulness, rapid eye movement and non-rapid eye movement sleep in human narcolepsy.

Our understanding of rapid eye movement (REM) sleep and how it is generated remains a topic of debate. Understanding REM sleep mechanisms is important because several sleep disorders result from disturbances in the neural circuits that control REM sleep and its characteristics. This review highlights recent work concerning how the central nervous system regulates REM sleep, and how the make up and breakdown of these REM sleep-generating circuits contribute to narcolepsy, REM sleep behaviour disorder and sleep apnea. A complex interaction between brainstem REM sleep core circuits and forebrain and hypothalamic structures is necessary to generate REM sleep. Cholinergic activation and GABAergic inhibition trigger the activation of subcoeruleus neurons, which form the core of the REM sleep circuit. Untimely activation of REM sleep circuits leads to cataplexy - involuntary muscle weakness or paralysis - a major symptom of narcolepsy. Degeneration of the REM circuit is associated with excessive muscle activation in REM sleep behaviour disorder. Inappropriate arousal from sleep during obstructive sleep apnea repeatedly disturbs the activity of sleep circuits, particularly the REM sleep circuit.

Sleep is prompted by natural cycles of activity in the brain and consists of two basic states: rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. REM sleep behavior disorder (RBD) is characterized by violent motor and vocal behavior during REM sleep which represents dream enactment. The normal loss of muscle tone, with the exception of respiratory, sphincter, extra ocular and middle ear muscles, is absent in patients with RBD. The origin of RBD is frequently unknown, but can be associated with degenerative neurological disorders, such as Parkinson's disease (PD). PD patients do not necessarily express features of RBD, which is identified in approximately third to a half of them. The aim of this study was to estimate the prevalence of RBD in a cohort of PD patients, as well as to identify risk-factors for its development. In the period from December 2010 to September 2011 we recruited 97 consecutive PD outpatients, treated in the Institute of Neurology, Clinical Center of Serbia, Belgrade. After establishing the diagnosis, all the patients filled out a specially constructed questionnaire with the following items: actual age, sex, age at disease onset, disease duration, form of the disease, type of treatment, duration of treatment, the presence of constipation, lessening of smell sense, and family history of PD. At entring the study, patients disability was scored using the Unified Parkinson's Disease Rating Scale (motor part - UPDRS). Cognitive abilities were assessed by the Mini Mental Status Examination (MMSE) scale, and depression symptoms by the 21-item Hamilton Depression Rating Scale (HDRS). The patients with PD were dichotomized to those with and without RBD using the RBD Questionnaire-Hong Kong (RBDQ-HK) in the manner of an interview. Forms of PD, mode of treatment, sex, constipation and family history were investigated using the Fishers χ2 test. Symptoms and treatment duration, the presence of smell disturbances, MMSE score, UPDRS motor score and HDRS score were analyzed by implementation of the Z-test. Actual age and age at disease onset were evaluated by the unpaired t-test. The RBD-positive group contained 15 (15.5%) patients, while in the rest of them (82/97), RBD was not identified (nonRBD group). There was no difference between the two groups considering gender distribution (p = 0.847), age (p = 0.577), age at disease onset (p = 0.141 ), duration. of PD (p = 0.069), family history (p = 0.591), type of initial symptoms (p = 0.899), constipation (p = 0.353), olfaction (p = 0.32) and MMSE scores (p = 0.217). The duration of treatment in the RBD group was longer than in the non-RBD group (9.4 ± 5.3 and 6.3 ± 3.9 years, respectively; p = 0.029), and the UPDRS motor score in the RBD group was higher (19.1 ± 9.4 and 12.7 ± 8.2, respectively; p = 0.013). Also, HDRS scores were higher in patients expressing RBD (10.1 ± 6.0 and 6.4 ± 4.5, respectively; p = 0.019). We found that 15.5% of the consecutive PD patients had RBD, and that the patients with RBD differed from the non-RBD ones regarding duration of treatment, disease and depressive symptoms severity.

The discovery of rapid eye movement (REM) sleep and, in particular, REM sleep behavior disorder (RBD) have brought elusive nightmarish experiences to scientific scrutiny. This article summarizes a century of sleep research to examine the maladies of dreaming, their pathophysiologic significance, and management. Under healthy physiologic conditions, REM sleep is characterized by vivid mentation combined with skeletal muscle paralysis. The loss of REM sleep atonia in RBD results in vivid, potentially injurious dream enactment to patients and bed partners. RBD is common, affecting at least 1% of the population and is primarily caused by α-synuclein pathology of REM sleep-related brainstem neurons. The majority of patients with RBD ultimately develop a neurodegenerative syndrome such as Parkinson disease, dementia with Lewy bodies, or multiple system atrophy. Among patients with Parkinson disease, RBD predicts an aggressive disease course with rapid cognitive, motor, and autonomic decline. RBD is diagnosed by the presence of dream enactment episodes (either recorded or clinically recalled) and physiologic evidence of REM sleep without atonia demonstrated on polysomnography. Bedroom safety is of paramount importance in the management of RBD while pharmacokinetic options include melatonin or clonazepam. The injurious dream enactment of RBD is common and treatable. It is a syndrome of α-synuclein pathology with most patients ultimately developing Parkinson disease, dementia with Lewy bodies, or a related disorder.

Biscarini F, Montini A, Antelmi E, Vandi S, Pizza F, Plazzi G. REM sleep behavior disorder with predominant nightmares in a patient with ischemic pontine lesions. J Clin Sleep Med. 2022;18(3):945-948.

Neurologists are often enlisted to help diagnose, evaluate, and manage a spectrum of abnormal spells during the night ranging from parasomnias to motor disturbance that span the sleep-wake cycle. Parasomnias are undesirable emotional or physical events that accompany sleep. These events typically occur during entry into sleep from wakefulness, or during arousals from sleep, and are often augmented by the sleep state. Some parasomnias, such as the rapid eye movement (REM) sleep behavior disorder may be extremely undesirable, while others such as somniloquy are often of little concern. The parasomnias include a spectrum of abnormal emotions, movements, behaviors, sensory perceptions, dream mentation, and autonomic activity. Basic physiologic drives, such as sex, hunger, and aggression, may manifest as sleep-related eating, sleep-related sexual behaviors, and sleep-related violence. Parasomnias have a very bizarre nature, but are readily explainable, diagnosable, and treatable. They are hypothesized to be due to changes in brain organization across multiple states of being, and are particularly apt to occur during the incomplete transition or oscillation from one sleep state to another. Parasomnias are often explained on the basis that wakefulness and sleep are not mutually exclusive states, and abnormal intrusion of wakefulness into non-REM (NREM) sleep produces arousal disorders, and intrusion of wakefulness into REM sleep produces REM sleep parasomnias and REM sleep behavior disorder (RBD). Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD), two closely related conditions that often result in disturbed sleep onset and sleep maintenance, are also reviewed in this article. Although the mechanisms that underlie idiopathic RLS or PLMD are not fully understood, there is currently substantial evidence that dopaminergic dysfunction is likely involved in both conditions. The discussion will conclude with the "other parasomnias" and sleep-related movement disorders of clinical interest to the neurologist.

Rapid eye movement (REM) sleep is a behavioural state characterized by activation of the cortical and hippocampal EEG, rapid eye movements and muscle atonia. For the past 30 years, the most widely accepted neural circuitry model for the regulation of REM sleep has emphasized reciprocal inhibitory interactions between pontine brainstem monoaminergic and cholinergic neurons. In general support of the reciprocal interaction model, neuropharmacological studies have shown that cholinergic agonists promote REM sleep and muscarinic antagonists and monoamines inhibit REM sleep. It has nevertheless proven difficult to reconcile both the theoretical framework of this model and the pharmacological data with the fact that selective lesions of either cholinergic or monoaminergic (noradrenergic, serotoninergic or dopaminergic) nuclei in the brainstem have relatively limited effects on REM sleep. Recent work by our laboratory has revealed the presence of non-cholinergic and non-monoaminergic mutually inhibitory REM-off and REM-on areas in the mesopontine tegmentum that may form the neuroanatomical basis of the switching circuitry for REM sleep. These findings posit a REM switching circuitry model that is analogous to an electronic 'flip-flop' switch. In this flip-flop switch arrangement, GABAergic REM-on neurons (located in the sublaterodorsal tegmental nucleus (SLD)) inhibit GABAergic REM-off neurons (located in the ventrolateral periaqueductal grey matter (vlPAG) and lateral pontine tegmentum (LPT)) and vice versa. In the REM-on area are two populations of glutamatergic neurons, the first of which projects to the basal forebrain and regulates EEG components of REM sleep and the second of which projects to the ventromedial medulla and spinal cord and regulates atonia during REM sleep. Our findings demonstrating independent pathways mediating atonia and the EEG components of REM provide a basis for their occasional dissociation in pathological states, e.g. REM sleep behaviour disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by complex behavior during REM sleep. The etiology of this disorder is still unknown, but a recent study showed that RBD precedes symptoms of Parkinson disease (PD) by several years, and in a previous study, we found reduced striatal dopamine transporters in idiopathic clinically manifest RBD. Hypothesizing that subclinical RBD shows a less severe reduction of striatal dopamine transporters than clinically manifest RBD, we studied striatal postsynaptic dopamine D2-receptors with (S)-2hydroxy-3iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide labeled with iodine 123 (IBZM) and the striatal presynaptic dopamine transporters with (N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane labeled with iodine 123 (IPT) using single-photon emission computed tomography (SPECT) in the following groups: 8 patients with idiopathic subclinical RBD, 8 patients with idiopathic clinically manifest RBD, 11 controls, and 8 patients with PD stage Hoehn & Yahr I. The IPT uptake was highest in controls. There was a significant decrease in IPT uptake from controls to patients with subclinical RBD, from patients with subclinical RBD to clinically manifest RBD, and from patients with clinically manifest RBD to patients with PD (controls: right = 4.07 +/- 0.29, left = 4.07 +/- 0.30; subclinical RBD: right = 3.56 +/- 0.21, left = 3.55 +/- 0.25; clinically manifest RBD: right = 3.18 +/- 0.43, left = 3.2 +/- 0.43; PD: ipsilateral to the clinically affected body side = 3.25 +/- 0.35, contralateral to the clinically affected body side = 2.51 +/- 0.28). Muscle activity during REM sleep lasting persistently longer than 0.5 seconds was independently associated with reduction of striatal dopamine transporters (P = 0.001). The IBZM uptake was not significantly different between the groups. This study suggests that there is a continuum of reduced striatal dopamine transporters involved in the pathophysiologic mechanisms causing increased muscle activity during REM sleep in patients with subclinical RBD.

The REM (Rapid Eye Movement) sleep as one of the five stages of sleep is the restorative part of the sleep cycle. During REM sleep, eyes move quickly in different directions and most dreams occur. Why people need REM sleep, why we dream, and what purpose our dreams serve are not known exactly. RBD (REM Behavior Disorder), a parasomnia, involves abnormal behavior during REM sleep phase, such as loss of muscle atonia. RBD is most often associated with elderly and in those with neurodegenerative disorders such as Parkinson’s disease, multiple system atrophy and Lewy body dementia. A portable and user friendly REM sleep detecting system is proposed based on differential shift of the eyeball localization using infrared optical sensor in this study. The system consists of an optical source/detector, current regulator, differential amplification, data acquisition, feature extraction, and classification parts, where a 730 nm light emitting diode and two photo detectors were used in the optical source/detector part, and wavelet transformation was applied in the feature extraction and the classification parts. In the feature extraction part, sleep time series data obtained from the data acquisition part was resampled to a sampling frequency of 256 Hz and then filtered with a 1st order 0.16 Hz high pass filter to remove dc offset and a 2nd order 60 Hz band limit filter. Finally, the filtered data was transformed using Matlab dwt function to detect periods of REM sleep. The performance of this REM sleep detecting system was evaluated with overnight recordings of 5 subjects. The results showed sensitivity of 85% and specificity of 92%, suggesting that this system can be a very practically efficient in automatic detection of REM sleep stages in a mobile environment.

ObjectiveCognitive impairment is a rapidly growing global public health problem in China and worldwide. In the recent decades, emerging studies have explored the associations between sleep disturbances and cognitive impairment. However, the variety of the results imply us that further studies should be conducted for the associations.MethodsThis is a cross-sectional study conducted between August and October 2018 in five cities in Hebei province, China. Subjects were 21,376 community residents. Cognitive impairment was screened by the Chinese version of the Mini-Mental State Examination (MMSE). Scales of Athens Insomnia Scale (AIS), Berlin Questionnaire (BQ), REM (rapid eye movement) Sleep Behavior Disorder Questionnaire (RBDQ-HK), Ullanlinna Narcolepsy Scale (CUNS), and Cambridge-Hopkins Restless Legs Syndrome Questionnaire (CH-RLSq) were used to access insomnia, sleep apnea, REM sleep behavior disorder, narcolepsy, and restless leg syndrome.ResultsThe mean ± SD (standard error) of MMSE, AIS, RBDQ-HK, and CUNS were 27.95 ± 4.79, 2.16 ± 3.39, 5.55 ± 7.75, and 3.76 ± 2.31, respectively. Among the participants, 10.6% and 1.5% of the participants were identified as having a high risk of sleep apnea and restless leg syndrome, respectively. The results of multiple linear regression showed that cognitive impairment was associated with insomnia (β = −0.037, p < 0.001) and narcolepsy (β = −0.023, p < 0.001). The association between sleep apnea (β = −0.002, p > 0.05), REM sleep behavior disorder (β = 0.006, p > 0.05), restless leg syndrome (β = −0.007, p > 0.05), and cognitive impairment were not supported. Other factors associated with cognitive impairment were gender, age, education level, married status, and region.ConclusionThis study provides some epidemiological evidence for the association between sleep disturbances and cognitive impairment among community residents in central China. In this study, the associations between insomnia, narcolepsy, and cognitive impairment were identified, but the associations between sleep apnea, REM sleep behavior disorder, narcolepsy, restless leg syndrome, and cognitive impairment were not supported among community residents.

Background:Rapid eye movement (REM) sleep behavior disorder (RBD) and obstructive sleep apnea (OSA) are the most common sleep disorders in Parkinson's disease (PD). The aim of this study was to identify whether RBD could alleviate OSA severity in PD patients and its effect on cognitive impairment.Methods:From February 2014 to May 2017, we recruited 174 PD patients from the Second Affiliated Hospital of Soochow University, all of whom underwent polysomnography (PSG). We collected clinical data, PSG results, and compared information between patients with and without RBD or OSA by analysis of covariance. We also investigated the effect of these sleep disorders on cognitive impairment using linear regression.Results:We grouped participants as follows: PD only (n = 53), PD + OSA (n = 29), PD + RBD (n = 61), and PD + RBD + OSA (n = 31). Minimum oxygen saturation (SaO2) during whole sleep and in REM sleep was higher in PD + RBD + OSA patients than that in PD + OSA patients. PD + RBD patients had worse Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) scores than those in the PD group (P < 0.001), especially in visuospatial/executive, attention, and memory functions. The PD + OSA group performed worse than the PD group in the delayed recall domain. After adjusting for age, sex, body mass index, education, disease severity, and other sleep disorders, MoCA was negatively associated with OSA (β = −0.736, P = 0.043) and RBD (β = −2.575,P < 0.001). The severity of RBD (tonic/phasic electromyography activity) and OSA (apnea-hypopnea index/oxygen desaturation index/minimum SaO2) were also associated with MoCA. The adjusted β values of RBD-related parameters were higher than that for OSA.Conclusions:We found that RBD alleviated OSA severity; however, RBD and OSA together exacerbated PD cognitive impairment. Further studies are needed to evaluate whether OSA treatment can improve cognition in PD.

Neural circuitry underlying REM sleep: A review of the literature and current concepts.

Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases