REM sleep behaviour disorder (RBD): Personal perspectives and research priorities.

The formal identification and naming of rapid eye movement (REM) sleep behaviour disorder (RBD) in 1985-1987 is described; the historical background of RBD from 1966 to 1985 is briefly discussed; and RBD milestones are presented. Current knowledge on RBD is identified with reference to recent comprehensive reviews, allowing for a focus on research priorities for RBD: factors and predictors of neurodegenerative phenoconversion from isolated RBD and patient enrolment in neuroprotective trials; isolated RBD clinical research cohorts; epidemiology of RBD; traumatic brain injury, post-traumatic stress disorder, RBD and neurodegeneration; depression, RBD and synucleinopathy; evolution of prodromal RBD to neurodegeneration; gut microbiome dysbiosis and colonic synuclein histopathology in isolated RBD; other alpha-synuclein research in isolated RBD; narcolepsy-RBD; dreams and nightmares in RBD; phasic REM sleep in isolated RBD; RBD, periodic limb movements, periodic limb movement disorder pseudo-RBD; other neurophysiology research in RBD; cardiac scintigraphy (123I-MIBG) in isolated RBD; brain magnetic resonance imaging biomarkers in isolated RBD; microRNAs as biomarkers in isolated RBD; actigraphic, other automated digital monitoring and machine learning research in RBD; prognostic counselling and ethical considerations in isolated RBD; and REM sleep basic science research. RBD research is flourishing, and is strategically situated at an ever-expanding crossroads of clinical (sleep) medicine, neurology, psychiatry and neuroscience.

Familial α-synucleinopathy spectrum features in patients with psychiatric REM sleep behaviour disorder.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the earliest and most specific prodromes of the α-synucleinopathies including Parkinson's disease (PD). It remains uncertain whether RBD occurring in the context of psychiatric disorders (psy-RBD), although very common, is merely a benign epiphenomenon of antidepressant treatment, or whether it harbours an underlying α-synucleinopathy. We hypothesised that patients with psy-RBD demonstrate a familial predisposition to an α-synucleinopathy. METHODS: In this case-control-family study, a combination of family history and family study method was used to measure the α-synucleinopathy spectrum features, which included RBD, neurodegenerative prodromal markers and clinical diagnoses of neurodegenerative disorders. We compared the risk of α-synucleinopathy spectrum features in the first-degree relatives (FDRs) of patients with psy-RBD, psychiatric controls and healthy controls. RESULTS: There was an increase of α-synucleinopathy spectrum features in the psy-RBD-FDRs, including possible and provisional RBD (adjusted HR (aHR)=2.02 and 6.05, respectively), definite RBD (adjusted OR=11.53) and REM-related phasic electromyographic activities, prodromal markers including depression (aHR=4.74) and probable subtle parkinsonism, risk of prodromal PD and clinical diagnosis of PD/dementia (aHR=5.50), as compared with healthy-control-FDRs. When compared with psychiatric-control-FDRs, psy-RBD-FDRs consistently presented with a higher risk for the diagnosis and electromyographic features of RBD, diagnosis of PD/dementia (aHR=3.91) and risk of prodromal PD. In contrast, psychiatric controls only presented with a familial aggregation of depression. CONCLUSION: Patients with psy-RBD are familially predisposed to α-synucleinopathy. The occurrence of RBD with major depression may signify a subtype of major depressive disorders with underlying α-synucleinopathy neurodegeneration. TRIAL REGISTRATION NUMBER: NCT03595475.

Severity of REM sleep without atonia correlates with measures of cognitive impairment and depressive symptoms in REM sleep behaviour disorder.

This study aimed to correlate REM sleep without atonia (RSWA) and neuropsychological data in patients with idiopathic/isolated REM sleep behaviour disorder (iRBD) and those with RBD associated with Parkinson's disease (PDRBD), in order to assess whether higher degrees of RSWA are related to poorer cognitive performance. A total of 142 subjects were enrolled: 48 with iRBD, 55 with PDRBD, and 39 PD without RBD (PDnoRBD). All participants underwent video-polysomnographic recording, clinical and neuropsychological assessment. RSWA was quantified according to two manual scoring methods (Montréal, SINBAR) and one automated (REM atonia index, RAI). Mild cognitive impairment (MCI) was diagnosed according to diagnostic criteria for MCI in Parkinson's disease. The relationship between neuropsychological scores and RSWA metrics was explored by multiple linear regression analysis and logistic regression models. Patients with iRBD showed significantly lower visuospatial functions and working memory, compared with the others. More severe RSWA was associated with a higher risk of reduced visuospatial abilities (OR 0.15), working memory (OR 2.48), attention (OR 2.53), and semantic fluency (OR 0.15) in the iRBD. In the whole group, a greater RSWA was associated with an increased risk for depressive symptoms (OR 3.6). A total of 57(40%) MCI subjects were found (17 iRBD, 26 PDRBD, and 14 PDnoRBD). Preserved REM-atonia was associated with a reduced odds of multi-domain MCI in the whole study population (OR 0.54). In conclusion, a greater severity of RSWA was associated with an increased risk for poor cognitive performance and depressive mood in patients with RBD. Moreover, higher RAI was associated with a lower risk of multi-domain MCI.

Ethical Aspects of Prodromal Synucleinopathy Prognostic Counseling.

Alpha-synucleinopathies can be identified in their prodromal phase, raising several ethical issues. In this review, we first provide definitions of prodromal α-synucleinopathies and discuss the importance of distinguishing between prodromes and risk factors. Next, we discuss the implications of a diagnosis of prodromal α-synucleinopathy and considerations regarding prognostic counseling in both clinical and research settings. We review available data on patient preferences regarding disclosure as well as providers' perspectives. We examine the pros and cons of disclosing a diagnosis of prodromal α-synucleinopathy, taking into consideration the differences between clinical and research settings. Asking about willingness to know in clinical and research settings and the shared decision-making process applied to prognostic counseling is discussed. Concerning research settings, ethical aspects regarding clinical trials are addressed. Availability of direct-to-consumer technologies will likely lead to novel contexts requiring prognostic counseling, and future neuroprotective or neuromodulating treatments may require further considerations on the timing, role, and importance of prognostic counseling. Recommendations on how to address ethical gaps should be a priority for patients, medical professional societies, and research workgroups. Ethical issues must be considered as an integral part of the overall clinical and research approach to prodromal synucleinopathies.

Parasomnias in patients with addictions-a systematic review.

Parasomnias are involuntary behaviors or subjective experiences during sleep. Our objective was to review existing information on the presence of parasomnias in patients with addictions or during treatment for addictions. Information about parasomnias related to rapid-eye-movement (REM) and non-REM sleep in patients with addictions, while using substances or in abstinence, was reviewed. A systematic search of published articles reporting parasomnias as a consequence of drug use or abuse was conducted in the PubMed and SciELO databases. The search for the studies was performed in three phases: (1) by title, (2) by abstract, and (3) by complete text. The search was performed independently by two researchers, who then compared their results from each screening phase. Seventeen articles were found. The consumption of alcohol was reported in association with arousal disorders, such as sexsomnia and sleep-related eating disorder; and REM sleep behavior disorder was reported during alcohol withdrawal. Cocaine abuse was associated with REM sleep behavior disorder with drug consumption dream content. Overall, we found that several types of parasomnias were very frequent in patients with addictions. To avoid accidents in bedroom, legal problems, and improve evolution and prognosis; must be mandatory to include security measures related to sleep period; avoid pharmacological therapy described as potential trigger factor; improve sleep hygiene; and give pharmacological and behavioral treatments for patients with these comorbid sleep disorders.

REM sleep behavior disorder as a complex condition with heterogeneous underlying disorders: clinical management and prognostic implications [Commentary].

PURPOSE: To review how REM sleep behavior disorder (RBD) is a complex condition with heterogeneous underlying disorders; and to review clinical management issues and prognostic implications. METHODS: PubMed literature search and contents from the first textbook of RBD (2018). RESULTS: RBD, with its core objective diagnostic feature of REM-without-atonia (RWA) documented by video-polysomnography, can emerge during the entire lifespan, and can initially present as an idiopathic (isolated) condition (iRBD), or can be associated with a broad spectrum of disorders including narcolepsy, alpha-synuclein neurodegenerative disorders (esp. Parkinson's disease [PD] and dementia with Lewy bodies [DLB]), paraneoplastic neurological syndromes and autoimmune disorders, CNS lesions (e.g., tumors, stroke), other neurological disorders, psychiatric disorders (PTSD, mood disorders), can be triggered by antidepressant/other medications, and can emerge acutely with drug withdrawal states, toxic-metabolic states, etc. Important clinical issues include the evolution of iRBD to PD/DLB in most middle-aged and older patients over a period of years to several decades, with compelling prognostic implications, along with the hope of enrolling these patients in future clinical trials to test promising disease-modifying therapies. Also, the strong link of RBD with narcolepsy needs further investigation. Parasomnia overlap disorder involves RBD and NREM parasomnias that can be idiopathic or linked with a broad range of clinical disorders. RBD usually responds to therapy consisting mainly of melatonin and/or clonazepam at bedtime. The complex associations of RBD with OSA are being increasingly investigated. RBD mimics with dream-enactment need to be recognized for diagnostic and management purposes, including severe OSA, NREM parasomnias, PLMD, nocturnal seizures, and other conditions. CONCLUSIONS: The clinical and research RBD fields span across the disciplines of neurology, pulmonary, psychiatry, psychology, and pediatric sleep medicine, along with physical medicine and rehabilitation medicine, other allied disciplines, and the basic and clinical neurosciences.

Clinical trials in REM sleep behavioural disorder: challenges and opportunities.

The rapid eye movement sleep behavioural disorder (RBD) population is an ideal study population for testing disease-modifying treatments for synucleinopathies, since RBD represents an early prodromal stage of synucleinopathy when neuropathology may be more responsive to treatment. While clonazepam and melatonin are most commonly used as symptomatic treatments for RBD, clinical trials of symptomatic treatments are also needed to identify evidence-based treatments. A comprehensive framework for both disease-modifying and symptomatic treatment trials in RBD is described, including potential treatments in the pipeline, cost-effective participant recruitment and selection, study design, outcomes and dissemination of results. For disease-modifying treatment clinical trials, the recommended primary outcome is phenoconversion to an overt synucleinopathy, and stratification features should be used to select a study population at high risk of phenoconversion, to enable more rapid clinical trials. For symptomatic treatment clinical trials, objective polysomnogram-based measurement of RBD-related movements and vocalisations should be the primary outcome measure, rather than subjective scales or diaries. Mobile technology to enable objective measurement of RBD episodes in the ambulatory setting, and advances in imaging, biofluid, tissue, and neurophysiological biomarkers of synucleinopathies, will enable more efficient clinical trials but are still in development. Increasing awareness of RBD among the general public and medical community coupled with timely diagnosis of these diseases will facilitate progress in the development of therapeutics for RBD and associated neurodegenerative disorders.

Firing a loaded gun during sleep in an elderly man with a "perfect storm" of risk factors including severe obstructive sleep apnea.

PURPOSE: We report a case of firing a loaded gun during sleep in a geriatric patient with undiagnosed major sleep disorders and multiple risk factors for sleep violence. Polysomnographic findings, diagnostic challenges, and forensic implications in this unprecedented geriatric case are discussed. METHODS: A 75-year-old employed man, married for 32 years, presented to a sleep center reporting to having fired a shot in his bedroom during sleep while his wife was away, without memory of hearing the gunshot. The day before the event, the patient had a normal life, apart from serious worries about recent nearby burglaries that prompted his sleeping with a loaded gun placed behind his bed. The patient underwent a sleep medicine workup, including nocturnal video polysomnography (vPSG). RESULTS: The patient and his wife were unaware of any sleep problems. Upon careful questioning, only mild daytime sleepiness and rare episodes of minor abnormal motor behavior were reported. At vPSG, sleep structure was markedly disrupted with only one clear sleep cycle with REM sleep that had preserved REM-atonia; severe obstructive sleep apnea and moderately severe periodic limb movement activity were documented. Brief abnormal movements from REM sleep without apparent precipitant were recorded. CPAP therapy was effective. CONCLUSIONS: In this case, there was a "perfect storm" of sleep and psychological risk factors that converged to strongly promote precipitous arousals with sleep-related violence in a patient with documented sleep motor dyscontrol. Primary care physicians, including geriatric specialists, should question patients and their spouses about any symptoms of sleep disorders.

Sporadic Nocturnal Frontal Lobe Epilepsy--Report on Two Cases and Review of the First Taiwanese Series of 10 Cases.

PURPOSE: To report two additional cases of sporadic (i.e. non-familial) Nocturnal Frontal Lobe Epilepsy (NFLE) and integrate these two cases within the first series of 10 cases of sporadic NFLE reported in Taiwanese patients, and compare the findings with familial NFLE and with findings from Caucasian NFLE patients. METHODS: Clinical interviews, neurological examinations, EEG, brain MRI, and overnight videopolysomnographic (vPSG) monitoring with EEG seizure montage, and treatment outcome. RESULTS: The two additional patients were 12 and 29 year old females manifesting their sporadic NFLE with paroxysmal arousals (PAs) and nocturnal paroxysmal dystonia (NPD), respectively, and also hypermotor seizure behavior in one of these patients. In the series of 10 Taiwanese cases, 3 were classified with PAs, and 7 with NPD. No patient had combined PA/NPD seizure types. Furthermore, 4 cases also demonstrated hypermotor seizure behavior. Gender ratio was four males to six females. Mean age of NFLE onset was 9.6 yrs (range, 1-23), mean age at initial presentation was 16.1 yrs (range,2-41), and mean age at latest follow-up was 23.1 yrs (range 11-45). Premorbid history was negative for any neurologic, medical or psychiatric disorder. MRI brain scan abnormalities with clinical correlates were found in two patient. During vPSG studies, four of ten patients with NFLE seizure events had concurrent epileptiform EEG activity, and two patients had interictal epileptiform EEG activity during their vPSG studies. No case had a spontaneous remission. Anticonvulsant therapy was highly effective in all ten cases (>75% reduction in seizure frequency). CONCLUSION: The two newly reported cases that were integrated into the first series of 10 Taiwanese patients with sporadic NFLE corresponds closely to previously reported sporadic and familial NFLE among Caucasian patients in Europe and North America. There was a high rate of sustained anticonvulsant treatment efficacy, particularly with carbamazepine, oxcarbamazepine, and topiramate. Also, 4 of the 10 patients had hypermotor manifestations (in part) of their NFLE (including one of the two newly reported cases), which are discussed in regards to the newly published entity of "Sleep-Related Hypermotor Epilepsy(1)."

The parasomnia defense in sleep-related homicide: A systematic review and a critical analysis of the medical literature.

This review critically analyzes the forensic application of the Parasomnia Defense in homicidal incidents, drawing from medical literature on disorders of arousal (DOA) and rapid-eye-movement sleep behavior disorder (RBD). A systematic search of PubMed, Scopus, Embase, and Cochrane databases was conducted until October 16, 2022. We screened English-language articles in peer-reviewed journals discussing murders committed during sleep with a Parasomnia Defense. We followed PRISMA guidelines, extracting event details, diagnosis methods, factors influencing the acts, perpetrator behavior, timing, motives, concealment, mental experiences, victim demographics, and court verdicts. Three sleep experts evaluated each case. We selected ten homicides, four attempted homicides, and one homicide/attempted homicide that met inclusion/exclusion criteria. Most cases were suspected DOA as unanimously confirmed by experts. RBD cases were absent. Among aggressors, a minority reported dream-like experiences. Victims were primarily female family members killed in or near the bed by hands and/or with sharp objects. Objective sleep data and important crime scene details were often missing. Verdicts were ununiform. Homicides during DOA episodes, though rare, are documented, validating the Parasomnia Defense's use in forensics. RBD-related fatal aggression seems very uncommon. However, cases often lack diagnostic clarity. We propose updated guidelines to enhance future reporting and understanding of such incidents.

Understanding Sexual Parasomnias: A Review of the Current Literature on Their Nature, Diagnosis, Impacts, and Management.

Sexual behavior during sleep, known as sexual parasomnias, has captured the interest of researchers and clinicians. These parasomnias involve various sexual activities that occur unconsciously during sleep. Although relatively rare, they can profoundly affect well-being and relationships and can carry legal consequences. Understanding their nature, prevalence, and causes is crucial for advancing knowledge in this field. This article revisits the topic of sexsomnia, presenting new data and discussing cases published from 2007 to 2023. By analyzing these cases, we aim to enhance recognition, diagnosis, and management of sexsomnia, reducing stigma and providing better support for affected individuals.

A case of accidental self-enucleation caused by obstructive sleep apnea.

A novel form of injury associated with obstructive sleep apnea (OSA) that was comorbid with obesity hypoventilation syndrome, and severe daytime somnolence is reported in a 55 year-old woman, manifesting as severe ocular and extra-ocular muscle injuries sustained from suddenly falling asleep and colliding with a sharp object, resulting in surgical enucleation of the right eye and orbital implant. The literature on injuries (falls, motor vehicle accidents) related to OSA and excessive day time sleepiness (EDS) is reviewed, along with the literature on injuries from OSA-related parasomnias. The diverse health hazards, including physical injury, associated with OSA-EDS, are emphasized, further encouraging the need to educate primary care providers on early detection of OSA with prompt treatment intervention.

Validation of electronic diagnostic codes for rapid eye movement sleep behavior disorder.

We investigated the accuracy of International Classification of Diseases (ICD) codes for the identification of Veterans with rapid eye movement (REM) sleep behavior disorder (RBD). The charts of 139 randomly sampled Veterans with ≥1 ICD-9 and ICD-10 code(s) for RBD were reviewed for documentation of a suspected, previous, or current diagnosis; clinical symptoms; and/or empiric treatments for this disorder. Notably, 71 (51.1%) of patients with RBD electronic diagnoses lacked polysomnography (PSG), and 29 (20.9%) had PSG reports without commentary on REM sleep without atonia (RSWA). Sleep centers are therefore encouraged to include a brief sentence in PSG report templates commenting on the presence/absence of RSWA.

Polysomnographic features associated with clonazepam and melatonin treatment in isolated REM sleep behavior disorder: Time for new therapeutic approaches?

AIMS: Although clonazepam (CLO) and melatonin (MLT) are the most frequently used treatments for REM sleep behavior disorder, the polysomnographic features associated with their use are little known. The aim of this study was to evaluate polysomnographic and clinical parameters of patients with idiopathic/isolated REM sleep behavior disorder (iRBD) treated chronically with CLO, sustained-release MLT, alone or in combination, and in a group of drug-free iRBD patients. METHODS: A total of 96 patients were enrolled: 43 drug-free, 21 with CLO (0.5-2 mg), 20 with sustained-release MLT (1-4 mg), and 12 taking a combination of them (same doses). Clinical variables and polysomnography were collected. RESULTS: Although clinical improvement was reported in all groups, MLT impacted sleep architecture more than the other treatments, with significant and large increase in N3 stage, moderate reduction in N2 and REM sleep, and moderate increase in REM latency. CLO moderately increased the percentage of both REM sleep and especially N2, while reducing N1 and wakefulness. Patients treated with both CLO and MLT did not show major changes in sleep architecture. CONCLUSION: These results suggest that the administration of MLT or CLO impacts (positively) on sleep parameters of iRBD patients. However, there is a need to better stratify patients, in order to treat them in a targeted manner, depending on the patient's individual sleep architecture and expected differential effects of these agents.

Comorbid neurotrauma increases neurodegenerative-relevant cognitive, motor, and autonomic dysfunction in patients with rapid eye movement sleep behavior disorder: a substudy of the North American Prodromal Synucleinopathy Consortium.

STUDY OBJECTIVES: Rapid eye movement sleep behavior disorder (RBD) is strongly associated with phenoconversion to an overt synucleinopathy, e.g. Parkinson's disease (PD), Lewy body dementia, and related disorders. Comorbid traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD)-henceforth "neurotrauma" (NT)-increase the odds of RBD by ~2.5-fold and are associated with an increased rate of service-connected PD in Veterans. Thus, RBD and NT are both independently associated with PD; however, it is unclear how NT influences neurological function in patients with RBD. METHODS: Participants ≥18 years with overnight polysomnogram-confirmed RBD were enrolled between 8/2018 to 4/2021 through the North American Prodromal Synucleinopathy Consortium. Standardized assessments for RBD, TBI, and PTSD history, as well as cognitive, motor, sensory, and autonomic function, were completed. This cross-sectional analysis compared cases (n = 24; RBD + NT) to controls (n = 96; RBD), matched for age (~60 years), sex (15% female), and years of education (~15 years). RESULTS: RBD + NT reported earlier RBD symptom onset (37.5 ±â€…11.9 vs. 52.2 ±â€…15.1 years of age) and a more severe RBD phenotype. Similarly, RBD + NT reported more severe anxiety and depression, greater frequency of hypertension, and significantly worse cognitive, motor, and autonomic function compared to RBD. No differences in olfaction or color vision were observed. CONCLUSIONS: This cross-sectional, matched case:control study shows individuals with RBD + NT have significantly worse neurological measures related to common features of an overt synucleinopathy. Confirmatory longitudinal studies are ongoing; however, these results suggest RBD + NT may be associated with more advanced neurological symptoms related to an evolving neurodegenerative process.

Validation of the RBD Symptom Severity Scale in the North American Prodromal Synucleinopathy Consortium.

BACKGROUND AND OBJECTIVES: REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment. The International RBD Study Group developed the RBD Symptom Severity Scale (RBDSSS) to assess symptom severity for clinical or research use. We assessed the psychometric and clinimetric properties of the RBDSSS in participants enrolled in the North American Prodromal Synucleinopathy (NAPS) Consortium for RBD. METHODS: NAPS participants, who have polysomnogram-confirmed RBD, and their bedpartners completed the RBDSSS (participant and bedpartner versions). The RBDSSS contains 8 questions to assess the frequency and severity/impact of (1) dream content, (2) vocalizations, (3) movements, and (4) injuries associated with RBD. Total scores for participant (maximum score = 54) and bedpartner (maximum score = 38) questionnaires were derived by multiplying frequency and severity scores for each question. The Clinical Global Impression Scale of Severity (CGI-S) and RBD symptom frequency were assessed by a physician during a semistructured clinical interview with participants and, if available, bedpartners. Descriptive analyses, correlations between overall scores, and subitems were assessed, and item response analysis was performed to determine the scale's validity. RESULTS: Among 261 study participants, the median (interquartile range) score for the RBDSSS-PT (participant) was 10 (4-18) and that for the RBDSSS-BP (bedpartner) was 8 (4-15). The median CGI-S was 3 (3-4), indicating moderate severity. RBDSSS-BP scores were significantly lower in women with RBD (6 vs 9, p = 0.02), while there were no sex differences in RBDSSS-PT scores (8 vs 10.5, p = 0.615). Positive correlations were found between RBDSSS-PT vs RBDSSS-BP (Spearman rs = 0.561), RBDSSS-PT vs CGI-S (rs = 0.556), and RBDSSS-BP vs CGI-S (rs = 0.491, all p < 0.0001). Item response analysis showed a high discriminatory value (range 1.40-2.12) for the RBDSSS-PT and RBDSSS-BP (1.29-3.47). DISCUSSION: We describe the RBDSSS with adequate psychometric and clinimetric properties to quantify RBD symptom severity and good concordance between participant and bedpartner questionnaires and between RBDSSS scores and clinician-assessed global severity.

A challenging case of sexsomnia in an adolescent female presenting with depressive-like symptoms.

Sleep-related sexualized behaviors occur in the parasomnia known as sexsomnia, recognized as a variant of confusional arousals in the International Classification of Sleep Disorders, third edition. These instinctive behaviors of a sexual nature emerge from deep non-rapid eye movement sleep, and patients often present with distinguishing features within this sleep disorder category. There are often adverse psychosocial consequences and not uncommonly medicolegal implications. While associations to psychiatric consequences from the sexsomnia have been demonstrated and efforts to further typify this condition have been made, sexsomnia remains incompletely characterized in the more than 200 published cases to date, with male predominance. We now present the first reported case of an adolescent female with sexsomnia that was triggered by the onset of Crohn's disease and its treatment with azathioprine and with interpersonal consequences leading to an initial psychiatric consultation on account of depressive symptoms. These symptoms were deemed to be secondary to the sexsomnia. In addition to describing unusual and clinically relevant features in this case of sexsomnia, this original case provides insights into triggers, predisposing factors, perpetuating factors, and therapeutic considerations that are important for raising awareness in sleep clinicians, primary care providers, and mental health professionals. CITATION: Brás J, Schenck CH, Andrade R, et al. A challenging case of sexsomnia in an adolescent female presenting with depressive-like symptoms. J Clin Sleep Med. 2023;19(10):1845-1847.

Effects of bupropion and SSRI antidepressants on leg movement activity and chin muscle tone during sleep in adolescents.

STUDY OBJECTIVES: To evaluate the effects of bupropion on periodic limb movements during sleep (PLMS) and chin electromyography tone in children taking it for their mood disorder, compared to the effects of selective serotonin reuptake inhibitors (SSRIs) and of bupropion combined with SSRIs. METHODS: Six adolescents (aged 16.0 ± 0.63 years) taking bupropion alone and 6 adolescents (aged 15.9 ± 1.36 years) taking bupropion in combination with an SSRI antidepressant were recruited, along with 10 adolescents (aged 16.2 ± 0.2 years) taking different SSRIs, and they were also enrolled together with 17 age- and sex-matched control patients (aged 15.5 ± 1.26 years). Polysomnographic studies were obtained, and participants' leg movement activity during sleep and muscle tone were assessed quantitatively (atonia index) during all sleep stages. RESULTS: Participants taking SSRIs showed PLMS indices significantly higher than those of control patients, whereas adolescents taking bupropion showed only slightly increased indexes of nonperiodic leg movements during sleep. No differences in PLMS were observed between adolescents taking bupropion alone or in association with SSRIs. The atonia index showed, within each sleep stage, the lowest values in the 2 groups taking SSRIs and the highest in the control patients; adolescents taking bupropion alone tended to show values slightly smaller than those of the control patients. CONCLUSIONS: We found that similar to adults, in adolescents SSRIs but not bupropion are associated with increased PLMS. Bupropion also seems to counteract the SSRI-induced increase of PLMS, when administered in combination; thus, the dopaminergic effect of bupropion seems to outmatch the antidopaminergic action of SSRIs. Conversely, bupropion does not counteract the effects of SSRIs on chin electromyography tone. CITATION: DelRosso LM, Mogavero MP, Fickensher A, Bruni O, Schenck CH, Ferri R. Effects of bupropion and SSRI antidepressants on leg movement activity and chin muscle tone during sleep in adolescents. J Clin Sleep Med. 2023;19(1):151-161.

Awake or Sleeping? Maybe Both A Review of Sleep-Related Dissociative States.

Recent studies have begun to understand sleep not only as a whole-brain process but also as a complex local phenomenon controlled by specific neurotransmitters that act in different neural networks, which is called "local sleep". Moreover, the basic states of human consciousness-wakefulness, sleep onset (N1), light sleep (N2), deep sleep (N3), and rapid eye movement (REM) sleep-can concurrently appear, which may result in different sleep-related dissociative states. In this article, we classify these sleep-related dissociative states into physiological, pathological, and altered states of consciousness. Physiological states are daydreaming, lucid dreaming, and false awakenings. Pathological states include sleep paralysis, sleepwalking, and REM sleep behavior disorder. Altered states are hypnosis, anesthesia, and psychedelics. We review the neurophysiology and phenomenology of these sleep-related dissociative states of consciousness and update them with recent studies. We conclude that these sleep-related dissociative states have a significant basic and clinical impact since their study contributes to the understanding of consciousness and the proper treatment of neuropsychiatric diseases.