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Current Neurology and Neuroscience... Dec 2023Since the formal discovery of rapid eye movement (REM) sleep in 1953, we have gained a vast amount of knowledge regarding the specific populations of neurons, their... (Review)
Review
PURPOSE OF REVIEW
Since the formal discovery of rapid eye movement (REM) sleep in 1953, we have gained a vast amount of knowledge regarding the specific populations of neurons, their connections, and synaptic mechanisms regulating this stage of sleep and its accompanying features. This article discusses REM sleep circuits and their dysfunction, specifically emphasizing recent studies using conditional genetic tools.
RECENT FINDINGS
Sublaterodorsal nucleus (SLD) in the dorsolateral pons, especially the glutamatergic subpopulation in this region (SLD), are shown to be indispensable for REM sleep. These neurons appear to be single REM generators in the rodent brain and may initiate and orchestrate all REM sleep events, including cortical and hippocampal activation and muscle atonia through distinct pathways. However, several cell groups in the brainstem and hypothalamus may influence SLD neuron activity, thereby modulating REM sleep timing, amounts, and architecture. Damage to SLD neurons or their projections involved in muscle atonia leads to REM behavior disorder, whereas the abnormal activation of this pathway during wakefulness may underlie cataplexy in narcolepsy. Despite some opposing views, it has become evident that SLD neurons are the sole generators of REM sleep and its associated characteristics. Further research should prioritize a deeper understanding of their cellular, synaptic, and molecular properties, as well as the mechanisms that trigger their activation during cataplexy and make them susceptible in RBD.
Topics: Humans; Cataplexy; Sleep, REM; REM Sleep Behavior Disorder; Brain; Narcolepsy
PubMed: 38060134
DOI: 10.1007/s11910-023-01322-x -
Brain : a Journal of Neurology Aug 2023Isolated rapid eye movement sleep behaviour disorder (iRBD) is a sleep disorder characterized by the loss of rapid eye movement sleep muscle atonia and the appearance of...
Isolated rapid eye movement sleep behaviour disorder (iRBD) is a sleep disorder characterized by the loss of rapid eye movement sleep muscle atonia and the appearance of abnormal movements and vocalizations during rapid eye movement sleep. It is a strong marker of incipient synucleinopathy such as dementia with Lewy bodies and Parkinson's disease. Patients with iRBD already show brain changes that are reminiscent of manifest synucleinopathies including brain atrophy. However, the mechanisms underlying the development of this atrophy remain poorly understood. In this study, we performed cutting-edge imaging transcriptomics and comprehensive spatial mapping analyses in a multicentric cohort of 171 polysomnography-confirmed iRBD patients [67.7 ± 6.6 (49-87) years; 83% men] and 238 healthy controls [66.6 ± 7.9 (41-88) years; 77% men] with T1-weighted MRI to investigate the gene expression and connectivity patterns associated with changes in cortical thickness and surface area in iRBD. Partial least squares regression was performed to identify the gene expression patterns underlying cortical changes in iRBD. Gene set enrichment analysis and virtual histology were then done to assess the biological processes, cellular components, human disease gene terms, and cell types enriched in these gene expression patterns. We then used structural and functional neighbourhood analyses to assess whether the atrophy patterns in iRBD were constrained by the brain's structural and functional connectome. Moreover, we used comprehensive spatial mapping analyses to assess the specific neurotransmitter systems, functional networks, cytoarchitectonic classes, and cognitive brain systems associated with cortical changes in iRBD. All comparisons were tested against null models that preserved spatial autocorrelation between brain regions and compared to Alzheimer's disease to assess the specificity of findings to synucleinopathies. We found that genes involved in mitochondrial function and macroautophagy were the strongest contributors to the cortical thinning occurring in iRBD. Moreover, we demonstrated that cortical thinning was constrained by the brain's structural and functional connectome and that it mapped onto specific networks involved in motor and planning functions. In contrast with cortical thickness, changes in cortical surface area were related to distinct genes, namely genes involved in the inflammatory response, and to different spatial mapping patterns. The gene expression and connectivity patterns associated with iRBD were all distinct from those observed in Alzheimer's disease. In summary, this study demonstrates that the development of brain atrophy in synucleinopathies is constrained by specific genes and networks.
Topics: Male; Humans; Female; Synucleinopathies; Alzheimer Disease; Cerebral Cortical Thinning; REM Sleep Behavior Disorder; Mitochondria; Atrophy
PubMed: 36826230
DOI: 10.1093/brain/awad044 -
Sleep Medicine Clinics Mar 2024Parasomnias are defined as abnormal movements or behaviors that occur in sleep or during arousals from sleep. Parasomnias vary in frequency from episodic events that... (Review)
Review
Parasomnias are defined as abnormal movements or behaviors that occur in sleep or during arousals from sleep. Parasomnias vary in frequency from episodic events that arise from incomplete sleep state transition. The framework by which parasomnias are categorized and diagnosed is based on the International Classification of Sleep Disorders-Third Edition, Text Revision (ICSD-3-TR), published by the American Academy of Sleep Medicine. The recent Third Edition, Text Revision (ICSD-3-TR) of the ICSD provides an expert consensus of the diagnostic requirements for sleep disorders, including parasomnias, based on an extensive review of the current literature.
Topics: Humans; Parasomnias; Sleep; Arousal
PubMed: 38368057
DOI: 10.1016/j.jsmc.2023.12.003 -
Pharmacology & Therapeutics Sep 2023Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by elevated motor behaviors and dream enactments in REM sleep, often preceding the... (Review)
Review
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by elevated motor behaviors and dream enactments in REM sleep, often preceding the diagnosis of Parkinson's disease (PD). As RBD could serve as a biomarker for early PD developments, pharmacological interventions targeting α-synuclein aggregation triggered RBD could be applied toward early PD progression. However, robust therapeutic guidelines toward PD-induced RBD are lacking, owing in part to a historical paucity of effective treatments and trials. We reviewed the bidirectional links between α-synuclein neurodegeneration, progressive sleep disorders, and RBD. We highlighted the correlation between RBD development, α-synuclein aggregation, and neuronal apoptosis in key brainstem regions involved in REM sleep atonia maintenance. The current pharmacological intervention strategies targeting RBD and their effects on progressive PD are discussed, as well as current treatments for progressive neurodegeneration and their effects on RBD. We also evaluated emerging and potential pharmacological solutions to sleep disorders and developing synucleinopathies. This review provides insights into the mechanisms and therapeutic targets underlying RBD and PD, and explores bidirectional treatment effects for both diseases, underscoring the need for further research in this area.
Topics: Humans; alpha-Synuclein; Parkinson Disease; REM Sleep Behavior Disorder; Sleep; Sleep Wake Disorders
PubMed: 37499913
DOI: 10.1016/j.pharmthera.2023.108498 -
Sleep Medicine Dec 2023Sleep disorders, including obstructive sleep apnea (OSA), restless leg syndrome (RLS) and insomnia, are present in chronic obstructive pulmonary disease (COPD) with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sleep disorders, including obstructive sleep apnea (OSA), restless leg syndrome (RLS) and insomnia, are present in chronic obstructive pulmonary disease (COPD) with varied prevalence. The aim of this systematic review and meta-analysis was to investigate prevalence of OSA, RLS and insomnia in patients with COPD and summarize their clinical characteristics.
METHODS
We searched PubMed, Web of Science and Scopus for eligible articles reporting the prevalence of OSA, RLS, and insomnia in COPD patients. The Newcastle‒Ottawa scale was applied for quality assessment. Odds ratios or mean differences with 95 % confidence intervals (CIs) were applied for the overall prevalence calculation and clinical characteristics assessment. Sensitivity analysis, subgroup analysis and meta-regression were conducted to evaluate the heterogeneity of the results.
RESULTS
Sixty articles reporting the prevalence of sleep disorders in patients with COPD were included, and the prevalence of OSA, RLS, and insomnia reached 29.1 %(95%CI 27.2%-30.9 %), 21.6 %(95%CI 11.8%-33.3 %) and 29.5 %(95%CI 16.9%-44.0 %), respectively. COPD patients with OSA were characterized by male sex (OR 1.631 95 % CI: 1.231-2.161), obesity(kg/m) (MD 4.435, 95 % CI 3.218-5.652), higher Epworth Sleepiness Scale (MD: 3.741, 95 % CI: 0.655-6.828, p = 0.018), better pulmonary function (MD 5.66, 95 % CI 3.546-7.774) and higher risks of hypertension (OR 1.933 95 % CI 1.382-2.70) and diabetes (OR 1.898 95 % CI 1.264-2.849). COPD patients with RLS were associated with a higher Epworth sleepiness scale (ESS) score (MD 3.444, 95 % CI 1.880-5.008) and a longer COPD duration(year) (MD: 3.656, 95 % CI: 2.209-5.103). COPD patients with insomnia were characterized by female sex(OR 0.556, 95%CI 0.545,0.567, p < 0.001).
CONCLUSION
Our study suggests that OSA, RLS and insomnia are common in COPD patients with specific clinical characteristics. Further studies are needed to explore the interactions between COPD and sleep disorders.
Topics: Humans; Male; Female; Sleep Initiation and Maintenance Disorders; Prevalence; Sleepiness; Pulmonary Disease, Chronic Obstructive; Sleep Apnea, Obstructive; Sleep Wake Disorders; Restless Legs Syndrome
PubMed: 37950939
DOI: 10.1016/j.sleep.2023.10.034 -
Sleep Medicine Nov 2023Non-rapid eye movement (NREM) parasomnias are often benign and transient, requiring no formal treatment. However, parasomnias can also be chronic, disrupt sleep quality,... (Review)
Review
BACKGROUND
Non-rapid eye movement (NREM) parasomnias are often benign and transient, requiring no formal treatment. However, parasomnias can also be chronic, disrupt sleep quality, and pose a significant risk of harm to the patient or others. Numerous behavioral strategies have been described for the management of NREM parasomnias, but there have been no published comprehensive reviews. This systematic review was conducted to summarize the range of behavioral and psychological interventions and their efficacy.
METHODS
We conducted a systematic search of the literature to identify all reports of behavioral and psychological treatments for NREM parasomnias (confusional arousals, sexsomnia, sleepwalking, sleep terrors, sleep-related eating disorder, parasomnia overlap disorder). This review was conducted in line with PRISMA guidelines. The protocol was registered with PROSPERO (CRD42021230360). The search was conducted in the following databases (initially on March 10, 2021 and updated February 24, 2023): Ovid (MEDLINE), Cochrane Library databases (Wiley), CINAHL (EBSCO), PsycINFO (EBSCO), and Web of Science (Clarivate). Given a lack of standardized quantitative outcome measures, a narrative synthesis approach was used. Risk of bias assessment used tools from Joanna Briggs Institute.
RESULTS
A total of 72 publications in four languages were included, most of which were case reports (68%) or case series (21%). Children were included in 32 publications and adults in 44. The most common treatment was hypnosis (33 publications) followed by various types of psychotherapy (31), sleep hygiene (19), education/reassurance (15), relaxation (10), scheduled awakenings (9), sleep extension/scheduled naps (9), and mindfulness (5). Study designs and inconsistent outcome measures limited the evidence for specific treatments, but some evidence supports multicomponent CBT, sleep hygiene, scheduled awakenings, and hypnosis.
CONCLUSIONS
This review highlights the wide breadth of behavioral and psychological interventions for managing NREM parasomnias. Evidence for the efficacy of these treatments is limited by the retrospective and uncontrolled nature of most research as well as the infrequent use of validated quantitative outcome measures. Behavioral and psychological treatments have been studied alone and in various combinations, and recent publications suggest a trend toward preference for multicomponent cognitive behavioral therapies designed to specifically target priming and precipitating factors of NREM parasomnias.
Topics: Adult; Child; Humans; Retrospective Studies; Parasomnias; Somnambulism; Sleep Arousal Disorders; Night Terrors
PubMed: 37716336
DOI: 10.1016/j.sleep.2023.09.004 -
Journal of Sleep Research Feb 2024Maternal depressive symptoms are associated with poorer sleep quality in their children. Although parasomnias can occur at any age, this group of sleep disorders is more...
Maternal depressive symptoms are associated with poorer sleep quality in their children. Although parasomnias can occur at any age, this group of sleep disorders is more common in children. The aim of this study was to assess whether maternal depression trajectories predict parasomnias at the age of 11 years. Data were from a Birth Cohort of 4231 individuals followed in the city of Pelotas, Brazil. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) at 12, 24, and 48 months, and 6 and 11 years postpartum. Maternal depression trajectories were calculated using a group-based modelling approach. Information on any parasomnias (confused arousals, sleepwalking, night terrors, and nightmares) was provided by the mother. Five trajectories of maternal depressive symptoms were identified: chronic-low (34.9%), chronic-moderate (41.4%), increasing (10.3%), decreasing (8.9%), and chronic-high (4.4%). The prevalence of any parasomnia at the age of 11 years was 16.8% (95% confidence interval [CI] 15.6%-18.1%). Confusional arousal was the most prevalent type of parasomnia (14.5%) and varied from 8.7% to 14.7%, 22.9%, 20.3%, and 27.5% among children of mothers at chronic-low, moderate-low, increasing, decreasing, and chronic-high trajectories, respectively (p < 0.001). Compared to children from mothers in the chronic-low trajectory, the adjusted prevalence ratio for any parasomnia was 1.58 (95% CI 1.29-1.94), 2.34 (95% CI 1.83-2.98), 2.15 (95% CI 1.65-2.81), and 3.07 (95% CI 2.31-4.07) among those from mothers in the moderate-low, increasing, decreasing, and chronic-high trajectory groups, respectively (p < 0.001). In conclusion, parasomnias were more prevalent among children of mothers with chronic symptoms of depression.
Topics: Child; Female; Humans; Depression; Parasomnias; Somnambulism; Night Terrors; Mothers; Sleep Arousal Disorders; Prevalence
PubMed: 36940922
DOI: 10.1111/jsr.13870 -
Continuum (Minneapolis, Minn.) Aug 2023This article reviews rapid eye movement (REM) sleep behavior disorder (RBD) and other REM sleep parasomnias, particularly recurrent isolated sleep paralysis and... (Review)
Review
OBJECTIVE
This article reviews rapid eye movement (REM) sleep behavior disorder (RBD) and other REM sleep parasomnias, particularly recurrent isolated sleep paralysis and nightmare disorder.
LATEST DEVELOPMENTS
People with RBD have dream enactment behaviors that can be distressing and cause injuries to themselves or a bed partner. Diagnosis of RBD still requires video polysomnography but new evaluative techniques are emerging. Automatic scoring of REM sleep without atonia, the polysomnographic RBD feature, has led to clearer diagnostic cutoff values. Isolated RBD is strongly linked with neurodegenerative disorders, particularly α-synucleinopathies, with a median latency to neurodegenerative disease diagnosis of 8 years. Mounting imaging, electrophysiologic, and pathologic evidence supports neurodegenerative changes in patients with isolated RBD. Safety precautions should be reviewed with patients to reduce the risk of injury. Clonazepam and melatonin are first-line agents for RBD symptoms, and rivastigmine appears to be beneficial for RBD in people with mild cognitive impairment. For nightmare disorder, image rehearsal therapy is effective and can be delivered through online platforms.
ESSENTIAL POINTS
While RBD symptoms can often be managed, patients with isolated RBD should be monitored for signs and symptoms of impending neurodegenerative disease. Individuals who wish to know about the associated risk should be counseled accordingly to allow planning and involvement in research if they choose. Exercise may have some neuroprotective effects, although no treatment has been shown to modify the neurodegenerative risk.
Topics: Humans; REM Sleep Behavior Disorder; Neurodegenerative Diseases; Parasomnias; REM Sleep Parasomnias; Cognitive Dysfunction
PubMed: 37590824
DOI: 10.1212/CON.0000000000001293 -
Revue Neurologique Oct 2023Nocturnal agitation refers to a broad spectrum of symptoms from simple movements to aggressive behaviors with partial or complete loss of awareness. An accurate... (Review)
Review
Nocturnal agitation refers to a broad spectrum of symptoms from simple movements to aggressive behaviors with partial or complete loss of awareness. An accurate identification of its etiology is critical for appropriate therapeutic intervention. In children and young adults, distinguishing between non-rapid eye movement (NREM) sleep parasomnias and psychogenic non-parasomniac manifestations, a condition known as sleep-related dissociative disorder (SRDD), can be challenging. This review aims to summarize current clinical, neurophysiological, and epidemiological knowledge on NREM parasomnia and SRDD, and to present the pathophysiological hypotheses underlying these nocturnal manifestations. Sleepwalking, sleep terror and confusional arousals are the three main presentations of NREM parasomnias and share common clinical characteristics. Parasomniac episodes generally occur 30minutes to three hours after sleep-onset, they are usually short, lasting no more than few minutes and involve non-stereotyped, clumsy behaviors with frequent amnesia. The prevalence of NREM parasomnia decreases from 15-30% in children to 2-4% in adults. Parasomniac episodes are incomplete awakening from the deepest NREM sleep and are characterized by a dissociated brain activity, with a wake-like activation in motor and limbic structures and a preserved sleep in the fronto-parietal regions. SRDD is a less known condition characterized by dramatic, often very long episodes with frequent aggressive and potentially dangerous behaviors. SRDD episodes frequently occur in quiet wakefulness before falling asleep. These dissociative manifestations are frequently observed in the context of psychological trauma. The pathophysiology of SRDD is poorly understood but could involve transient changes in brain connectivity due to labile sleep-wake boundaries in predisposed individuals. We hypothesize that SRDD and NREM parasomnia are forms of sleep-related dissociative states favored by a sleep-wake state dissociation during sleep-onset and awakening process, respectively.
Topics: Child; Young Adult; Humans; Parasomnias; Sleep Arousal Disorders; Dissociative Disorders; Movement; Sleep
PubMed: 37625976
DOI: 10.1016/j.neurol.2023.07.003