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Revue Neurologique Oct 2023Narcolepsy type 1 (NT1) and type 2 (NT2), also known as narcolepsy with and without cataplexy, are sleep disorders that benefited from major scientific advances over the... (Review)
Review
Narcolepsy type 1 (NT1) and type 2 (NT2), also known as narcolepsy with and without cataplexy, are sleep disorders that benefited from major scientific advances over the last two decades. NT1 is caused by the loss of hypothalamic neurons producing orexin/hypocretin, a neurotransmitter regulating sleep and wake, which can be measured in the cerebrospinal fluid (CSF). A low CSF level of hypocretin-1/orexin-A is a highly specific and sensitive biomarker, sufficient to diagnose NT1. Orexin-deficiency is responsible for the main NT1 symptoms: sleepiness, cataplexy, disrupted nocturnal sleep, sleep-related hallucinations, and sleep paralysis. In the absence of a lumbar puncture, the diagnosis is based on neurophysiological tests (nocturnal and diurnal) and the presence of the pathognomonic symptom cataplexy. In the revised version of the International Classification of sleep Disorders, 3rd edition (ICSD-3-TR), a sleep onset rapid eye movement sleep (REM) period (SOREMP) (i.e. rapid occurrence of REM sleep) during the previous polysomnography may replace the diurnal multiple sleep latency test, when clear-cut cataplexy is present. A nocturnal SOREMP is very specific but not sensitive enough, and the diagnosis of cataplexy is usually based on clinical interview. It is thus of crucial importance to define typical versus atypical cataplectic attacks, and a list of clinical features and related degrees of certainty is proposed in this paper (expert opinion). The time frame of at least three months of evolution of sleepiness to diagnose NT1 was removed in the ICSD-3-TR, when clear-cut cataplexy or orexin-deficiency are established. However, it was kept for NT2 diagnosis, a less well-characterized disorder with unknown clinical course and absence of biolo biomarkers; sleep deprivation, shift working and substances intake being major differential diagnoses. Treatment of narcolepsy is nowadays only symptomatic, but the upcoming arrival of non-peptide orexin receptor-2 agonists should be a revolution in the management of these rare sleep diseases.
Topics: Humans; Cataplexy; Orexins; Sleepiness; Narcolepsy; Sleep
PubMed: 37634997
DOI: 10.1016/j.neurol.2023.08.001 -
Mayo Clinic Proceedings May 2021Excessive daytime sleepiness (EDS) is a highly prevalent condition that is associated with significant morbidity. The causes of EDS are varied, and include inadequate... (Review)
Review
Excessive daytime sleepiness (EDS) is a highly prevalent condition that is associated with significant morbidity. The causes of EDS are varied, and include inadequate sleep, sleep disordered breathing, circadian rhythm sleep-wake disorders, and central disorders of hypersomnolence (narcolepsy, idiopathic hypersomnia, and Kleine-Levin syndrome). Additionally, EDS could represent a symptom of an underlying medical or psychiatric disorder. Assessment of EDS includes a thorough sleep, medical, and psychiatric history, targeted clinical examination, and appropriate use of actigraphy to measure sleep duration and sleep-wake patterns, polysomnography to assess for associated conditions such as sleep-related breathing disorders or other factors that might disrupt nighttime sleep, multiple sleep latency testing to ascertain objective sleepiness and diagnose central disorders of hypersomnolence, and measurement of cerebrospinal fluid hypocretin-1 concentration. Treatment of EDS secondary to central disorders of hypersomnolence is primarily pharmacologic with wakefulness-promoting agents such as modafinil, stimulants such as methylphenidate and amphetamines, and newer agents specifically designed to improve wakefulness; behavioral interventions can provide a useful adjunct to pharmacologic treatment. When excessive sleepiness is secondary to other conditions, the treatment should focus on targeting the primary disorder. This review discusses current epidemiology, provides guidance on clinical assessments and testing, and discusses the latest treatment options. For this review, we collated the latest evidence using the search terms excessive sleepiness, hypersomnia, hypersomnolence, treatment from PubMed and MEDLINE and the latest practice parameters from the American Academy of Sleep Medicine.
Topics: Combined Modality Therapy; Disorders of Excessive Somnolence; Humans; Risk Factors; Treatment Outcome
PubMed: 33840518
DOI: 10.1016/j.mayocp.2020.08.033 -
Respiratory Investigation Jan 2022The prevalence of sleep disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously...
The prevalence of sleep disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared in order to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Because sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.
Topics: Adult; Continuous Positive Airway Pressure; Female; Humans; Male; Prevalence; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Surveys and Questionnaires
PubMed: 34986992
DOI: 10.1016/j.resinv.2021.08.010 -
European Respiratory Review : An... Jun 2021Obstructive sleep apnoea (OSA) is a common sleep disorder with a high social and economic burden. Thus, early prediction and diagnosis of OSA are important. Changes in... (Review)
Review
INTRODUCTION
Obstructive sleep apnoea (OSA) is a common sleep disorder with a high social and economic burden. Thus, early prediction and diagnosis of OSA are important. Changes in metabolism and the microbiome may serve as biomarkers for OSA. Herein, we review the literature on the metabolomic and microbiome changes associated with OSA, and identify the metabolites and microorganisms involved.
METHODS
We searched the PUBMED and EMBASE electronic databases using the following terms: "obstructive sleep apnea", "OSA", "sleep disordered breathing", "SDB", "intermittent hypoxia", "sleep fragmentation", and either "metabolomics" or "microbiome". In total, 273 papers were identified, of which 28 were included in our study.
RESULTS
Changes in the levels of certain metabolites related to fatty acid, carbohydrate and amino acid metabolism were associated with the incidence of OSA. The diversity and abundance of microflora, particularly Firmicutes and Bacteroidetes, were altered in humans and rodents with OSA.
CONCLUSIONS
Certain changes in metabolism and the microbiota play an integral role in the pathophysiology of OSA and OSA-induced cardiovascular complications. Metabolomic and microbiome biomarkers shed light on the pathogenesis of OSA, and facilitate early diagnosis and treatment.
Topics: Biomarkers; Humans; Metabolomics; Microbiota; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
PubMed: 33980666
DOI: 10.1183/16000617.0220-2020 -
Sleep Medicine Reviews Feb 2023Repetitive transcranial magnetic stimulation (rTMS) is a widely used non-invasive neuromodulatory technique. When applied in sleep medicine, the main hypothesis... (Review)
Review
Repetitive transcranial magnetic stimulation (rTMS) is a widely used non-invasive neuromodulatory technique. When applied in sleep medicine, the main hypothesis explaining its effects concerns the modulation of synaptic plasticity and the strength of connections between the brain areas involved in sleep disorders. Recently, there has been a significant increase in the publication of rTMS studies in primary sleep disorders. A multi-database-based search converges on the evidence that rTMS is safe and feasible in chronic insomnia, obstructive sleep apnea syndrome (OSAS), restless legs syndrome (RLS), and sleep deprivation-related cognitive deficits, whereas limited or no data are available for narcolepsy, sleep bruxism, and REM sleep behavior disorder. Regarding efficacy, the stimulation of the dorsolateral prefrontal cortex bilaterally, right parietal cortex, and dominant primary motor cortex (M1) in insomnia, as well as the stimulation of M1 leg area bilaterally, left primary somatosensory cortex, and left M1 in RLS reduced subjective symptoms and severity scale scores, with effects lasting for up to weeks; conversely, no relevant effect was observed in OSAS and narcolepsy. Nevertheless, several limitations especially regarding the stimulation protocols need to be considered. This review should be viewed as a step towards the further contribution of individually tailored neuromodulatory techniques for sleep disorders.
Topics: Humans; Transcranial Magnetic Stimulation; Brain; Restless Legs Syndrome; Sleep Apnea, Obstructive; Sleep Initiation and Maintenance Disorders; Narcolepsy; Sleep Wake Disorders
PubMed: 36563570
DOI: 10.1016/j.smrv.2022.101735 -
International Journal of Environmental... Sep 2019The obstructive sleep apnea syndrome (OSAS) represents only part of a large group of pathologies of variable entity called respiratory sleep disorders (RSD) which... (Review)
Review
The obstructive sleep apnea syndrome (OSAS) represents only part of a large group of pathologies of variable entity called respiratory sleep disorders (RSD) which include simple snoring and increased upper airway resistance syndrome (UARS). Although the etiopathogenesis of adult OSAS is well known, many aspects of this syndrome in children are still debated. Its prevalence is about 2% in children from 2 to 8 years of age, mostly related to the size of the upper airways adenoid tissue. Several risk factors linked to the development of OSAS are typical of the pediatric age. The object of this paper is to analyze the state of the art on this specific topic, discussing its implications in terms of diagnosis and management.
Topics: Child; Child, Preschool; Humans; Prevalence; Risk Factors; Sleep Apnea, Obstructive
PubMed: 31487798
DOI: 10.3390/ijerph16183235 -
Current Opinion in Pulmonary Medicine Nov 2020The purpose of this review is to describe the variability of obstructive sleep apnea (OSA), both from a standpoint of underlying mechanisms and in terms of clinical... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to describe the variability of obstructive sleep apnea (OSA), both from a standpoint of underlying mechanisms and in terms of clinical manifestations.
RECENT FINDINGS
Recent data suggest that not all patients with sleep apnea get their disease for the same reason. As such, no one variable is effective at defining which patients do or do not have sleep apnea. Identifying the mechanism(s) underlying OSA for an individual is helpful as it can help to determine whether personalized therapy could be developed based on an individual's characteristics. In addition, these underlying mechanisms may be helpful in predicting response to therapy and prognosticating regarding future complications.
SUMMARY
OSA is a heterogeneous disease with highly varying underlying mechanisms. OSA has variable clinical manifestations with definable subsets having risk of particular complications. Future studies will be helpful to identify mechanisms underlying OSA using clinically accessible tools and then using these data to focus individualized treatment approaches.
Topics: Humans; Phenotype; Sleep Apnea, Obstructive
PubMed: 32890019
DOI: 10.1097/MCP.0000000000000724 -
Annals of the American Thoracic Society May 2021Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other... (Review)
Review
Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other aspects of well-being. Although EDS can be reduced with primary OSA treatment, such as continuous positive airway pressure (CPAP) therapy, a significant proportion of patients continue to experience EDS despite receiving optimized therapy for OSA. This article reviews the pathophysiology and clinical evaluation and management of EDS in patients with OSA. The mechanisms underlying EDS in CPAP-treated patients remain unclear. Experimental risk factors include chronic intermittent hypoxia and sleep fragmentation, which lead to oxidative injury and changes in neurons and brain circuit connectedness involving noradrenergic and dopaminergic neurotransmission in wake-promoting regions of the brain. In addition, neuroimaging studies have shown alterations in the brain's white matter and gray matter in patients with OSA and EDS. Clinical management of EDS begins with ruling out other potential causes of EDS and evaluating its severity. Tools to evaluate EDS include objective and self-reported assessments of sleepiness, as well as cognitive assessments. Patients who experience residual EDS despite primary OSA therapy may benefit from wake-promoting pharmacotherapy. Agents that inhibit reuptake of dopamine or of dopamine and norepinephrine (modafinil/armodafinil and solriamfetol, respectively) have demonstrated efficacy in reducing EDS and improving quality of life in patients with OSA. Additional research is needed on the effects of wake-promoting treatments on cognition in these patients and to identify individual or disorder-specific responses.
Topics: Continuous Positive Airway Pressure; Disorders of Excessive Somnolence; Humans; Modafinil; Quality of Life; Sleep Apnea, Obstructive
PubMed: 33621163
DOI: 10.1513/AnnalsATS.202006-696FR -
Chest Sep 2021Delirium is a deleterious condition affecting up to 60% of patients in the surgical ICU (SICU). Few SICU-focused delirium interventions have been implemented, including... (Observational Study)
Observational Study
BACKGROUND
Delirium is a deleterious condition affecting up to 60% of patients in the surgical ICU (SICU). Few SICU-focused delirium interventions have been implemented, including those addressing sleep-wake disruption, a modifiable delirium risk factor common in critically ill patients.
RESEARCH QUESTION
What is the effect on delirium and sleep quality of a multicomponent nonpharmacologic intervention aimed at improving sleep-wake disruption in patients in the SICU setting?
STUDY DESIGN AND METHODS
Using a staggered pre-post design, we implemented a quality improvement intervention in two SICUs (general surgery or trauma and cardiovascular) in an academic medical center. After a preintervention (baseline) period, a multicomponent unit-wide nighttime (ie, efforts to minimize unnecessary sound and light, provision of earplugs and eye masks) and daytime (ie, raising blinds, promotion of physical activity) intervention bundle was implemented. A daily checklist was used to prompt staff to complete intervention bundle elements. Delirium was evaluated twice daily using the Confusion Assessment Method for the Intensive Care Unit. Patient sleep quality ratings were evaluated daily using the Richards-Campbell Sleep Questionnaire (RCSQ).
RESULTS
Six hundred forty-six SICU admissions (332 baseline, 314 intervention) were analyzed. Median age was 61 years (interquartile range, 49-70 years); 35% of the cohort were women and 83% were White. During the intervention period, patients experienced fewer days of delirium (proportion ± SD of ICU days, 15 ± 27%) as compared with the preintervention period (20 ± 31%; P = .022), with an adjusted pre-post decrease of 4.9% (95% CI, 0.5%-9.2%; P = .03). Overall RCSQ-perceived sleep quality ratings did not change, but the RCSQ noise subscore increased (9.5% [95% CI, 1.1%-17.5%; P = .02).
INTERPRETATION
Our multicomponent intervention was associated with a significant reduction in the proportion of days patients experienced delirium, reinforcing the feasibility and effectiveness of a nonpharmacologic sleep-wake bundle to reduce delirium in critically ill patients in the SICU.
TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT03313115; URL: www.clinicaltrials.gov.
Topics: Cardiology Service, Hospital; Critical Care; Critical Illness; Delirium; Dyssomnias; Female; Humans; Intensive Care Units; Light Pollution; Male; Middle Aged; Noise; Outcome and Process Assessment, Health Care; Patient Care Bundles; Protective Devices; Quality Improvement; Sleep Quality; Sleep Wake Disorders
PubMed: 33773988
DOI: 10.1016/j.chest.2021.03.030 -
Archivos de Bronconeumologia Jan 2023Conventional measures of obstructive sleep apnea (OSA) severity, such as the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) are commonly used to quantify...
Conventional measures of obstructive sleep apnea (OSA) severity, such as the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) are commonly used to quantify OSA severity and guide therapeutical decision-making processes. However, it is widely recognized that both AHI and ODI have important limitations and novel physiologically-informed metrics are needed to better capture the severity of OSA and characterize its physiological consequences, particularly the severity of recurrent nocturnal hypoxemia, ensuing the respiratory events. According to recent studies, the sleep apnea-specific "hypoxic burden (HB)", defined as the sum of individual areas under the oxygen desaturation curve, has shown some promise in identifying high risk individuals with OSA. In addition to the frequency of respiratory events, HB capture the depth and duration of OSA-related hypoxemia that may prove to be important disease characterizing features, not captured by the conventional "frequency-based" metrics, such as AHI and ODI. In this "perspective" paper the methods to quantify the HB, its characteristics, associations with health outcomes, and its limitations will be discussed.
Topics: Humans; Polysomnography; Sleep Apnea, Obstructive; Sleep Apnea Syndromes; Hypoxia; Oxygen
PubMed: 36115739
DOI: 10.1016/j.arbres.2022.08.005