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Sleep Medicine Clinics Jun 2023Narcolepsy types 1 and 2 and idiopathic hypersomnia are primary Central Nervous System (CNS) disorders of hypersomnolence characterized by profound daytime sleepiness... (Review)
Review
Narcolepsy types 1 and 2 and idiopathic hypersomnia are primary Central Nervous System (CNS) disorders of hypersomnolence characterized by profound daytime sleepiness and/or excessive sleep need. Onset of symptoms begins typically in childhood or adolescence, and children can have unique presentations compared with adults. Narcolepsy type 1 is likely caused by immune-mediated loss of orexin (hypocretin) neurons in the hypothalamus; however, the causes of narcolepsy type 2 and idiopathic hypersomnia are unknown. Existing treatments improve daytime sleepiness and cataplexy but there is no cure for these disorders.
Topics: Adult; Adolescent; Child; Humans; Idiopathic Hypersomnia; Narcolepsy; Disorders of Excessive Somnolence
PubMed: 37120161
DOI: 10.1016/j.jsmc.2023.01.003 -
Seminars in Pediatric Neurology Dec 2023Daytime sleepiness is common amongst children and adolescents. Inadequate sleep duration, inappropriate school start times, and the delay in sleep phase of adolescence... (Review)
Review
Daytime sleepiness is common amongst children and adolescents. Inadequate sleep duration, inappropriate school start times, and the delay in sleep phase of adolescence may all contribute. Nocturnal sleep disruption due to sleep disorders such as obstructive sleep apnea or restless legs syndrome/periodic limb movement disorder may also lead to daytime sleepiness. Profound sleepiness however, when occurring in the setting of adequate sleep duration, is rare amongst children and adolescents and may prompt consideration of a central disorder of hypersomnolence (CDH). Narcolepsy is the archetypal and most studied form of CDH and a detailed review of the presentation, evaluation, treatment of narcolepsy is included separately in this edition of Seminars in Pediatric Neurology. In addition to narcolepsy, 2 other forms of primary CDH exist, idiopathic hypersomnia (IH) and Kleine-Levin syndrome (KLS). Onset of IH and KLS occurs most frequently during the pediatric age range and presentation may include signs of encephalopathy in addition to hypersomnolence. As such, they are of particular relevance to pediatric neurology and associated fields. Unfortunately, when compared to narcolepsy little is known about IH and KLS, at both the physiologic and clinical level. This review will focus on the presentation, evaluation, and management of idiopathic hypersomnia and Kleine-Levin syndrome in the pediatric population.
Topics: Adolescent; Child; Humans; Kleine-Levin Syndrome; Idiopathic Hypersomnia; Disorders of Excessive Somnolence; Narcolepsy; Brain Diseases
PubMed: 38065631
DOI: 10.1016/j.spen.2023.101082 -
The Neuroscientist : a Review Journal... Aug 2020Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis... (Review)
Review
Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis of neurological disorders, including sleep disorders. At present, the diagnosis of narcolepsy and primary hypersomnias is largely limited to subjective assessments and objective measurements of behavior and sleep physiology. In this review, we focus on recent neuroimaging findings that provide insight into the neural basis of narcolepsy and the primary hypersomnias Kleine-Levin syndrome and idiopathic hypersomnia. We describe the role of neuroimaging in confirming previous genetic, neurochemical, and neurophysiological findings and highlight studies that permit a greater understanding of the symptoms of these sleep disorders. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps, and the potential role for neuroimaging in understanding the pathogenesis and clinical features of narcolepsy and primary hypersomnias.
Topics: Animals; Disorders of Excessive Somnolence; Humans; Kleine-Levin Syndrome; Narcolepsy; Nervous System Diseases; Neuroimaging; Sleep
PubMed: 32111133
DOI: 10.1177/1073858420905829 -
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 -
The Psychiatric Clinics of North America Dec 2015Primary sleep disorders include those not attributable to another medical or psychiatric condition: insomnia disorder, hypersomnolence disorder, narcolepsy, obstructive... (Review)
Review
Primary sleep disorders include those not attributable to another medical or psychiatric condition: insomnia disorder, hypersomnolence disorder, narcolepsy, obstructive sleep apnea hypopnea syndrome, central sleep apnea syndrome, and the parasomnias. They are commonly encountered and are comorbid with many psychiatric disorders. It is important to recognize these disorders and be comfortable treating them or to know when to refer to a sleep disorders center and sleep specialist. Treatment of a comorbid sleep disorder can improve the overall quality of life, symptoms in mood disorders, and symptoms of excessive daytime sleepiness, and decrease cardiovascular morbidity and mortality.
Topics: Disorders of Excessive Somnolence; Humans; Narcolepsy; Parasomnias; Restless Legs Syndrome; Risk Factors; Sleep Apnea Syndromes; Sleep Initiation and Maintenance Disorders
PubMed: 26600103
DOI: 10.1016/j.psc.2015.08.002 -
Nature Reviews. Immunology Jan 2024Narcolepsy type 1 (NT1) is a chronic sleep disorder resulting from the loss of a small population of hypothalamic neurons that produce wake-promoting hypocretin (HCRT;... (Review)
Review
Narcolepsy type 1 (NT1) is a chronic sleep disorder resulting from the loss of a small population of hypothalamic neurons that produce wake-promoting hypocretin (HCRT; also known as orexin) peptides. An immune-mediated pathology for NT1 has long been suspected given its exceptionally tight association with the MHC class II allele HLA-DQB1*06:02, as well as recent genetic evidence showing associations with polymorphisms of T cell receptor genes and other immune-relevant loci and the increased incidence of NT1 that has been observed after vaccination with the influenza vaccine Pandemrix. The search for both self-antigens and foreign antigens recognized by the pathogenic T cell response in NT1 is ongoing. Increased T cell reactivity against HCRT has been consistently reported in patients with NT1, but data demonstrating a primary role for T cells in neuronal destruction are currently lacking. Animal models are providing clues regarding the roles of autoreactive CD4 and CD8 T cells in the disease. Elucidation of the pathogenesis of NT1 will allow for the development of targeted immunotherapies at disease onset and could serve as a model for other immune-mediated neurological diseases.
Topics: Animals; Humans; CD8-Positive T-Lymphocytes; Narcolepsy; Alleles
PubMed: 37400646
DOI: 10.1038/s41577-023-00902-9 -
Frontiers in Immunology 2022A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the...
A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the potential causative relationship between them. In this study, we selected genetic instruments for sleep traits from pooled data from published genome-wide association studies (GWAS). Independent genetic variants associated with six sleep-related traits (chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, and daytime sleepiness) were selected as instrumental variables. A two-sample Mendelian randomization (TSMR) study was first conducted to assess the causal relationship between sleep traits and SLE (7219 cases versus 15,991 controls). The reverse MR analysis was then used to infer the causal relationship between SLE and sleep traits. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were applied to perform the primary MR analysis. MR Egger regression and the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were used to detect horizontal pleiotropy, and Cochran's was used to detect heterogeneity. In studies of the effect of sleep traits on SLE risk, the IVW method demonstrated no causal relationship between chronotype, sleep duration, short sleep duration, long sleep duration, insomnia, daytime sleepiness and SLE risk. The remaining three methods agreed with the results of IVW. In studies of the effect of SLE on the risk of sleep traits, neither IVW, MR Egger, Weighted median, nor Weighted mode methods provided evidence of a causal relationship between SLE and the risk of sleep traits. Overall, our study found no evidence of a bidirectional causal relationship between genetically predicted sleep traits and SLE.
Topics: Disorders of Excessive Somnolence; Genome-Wide Association Study; Humans; Lupus Erythematosus, Systemic; Mendelian Randomization Analysis; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 35784289
DOI: 10.3389/fimmu.2022.918749 -
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 -
Current Neurology and Neuroscience... Mar 2006Hypersomnia includes a group of disorders in which the primary complaint is excessive daytime sleepiness. Chronic hypersomnia is characterized by at least 3 months of... (Review)
Review
Hypersomnia includes a group of disorders in which the primary complaint is excessive daytime sleepiness. Chronic hypersomnia is characterized by at least 3 months of excessive sleepiness prior to diagnosis and may affect 4% to 6% of the population. The severity of daytime sleepiness needs to be quantified by subjective scales (at least the Epworth sleepiness scale) and objective tests such as the multiple sleep latency test. Chronic hypersomnia does not correspond to an individual clinical entity but includes numerous different etiologies of hypersomnia as recently reported in the revised International Classification of Sleep Disorders. This review details most of those disorders, including narcolepsy with and without cataplexy, idiopathic hypersomnia with and without long sleep time, recurrent hypersomnia, behaviorally induced insufficient sleep syndrome, hypersomnia due to medical condition, hypersomnia due to drug or substance, hypersomnia not due to a substance or known physiologic condition, and also sleep-related disordered breathing and periodic leg movement disorders.
Topics: Chronic Disease; Diagnosis, Differential; Disorders of Excessive Somnolence; Humans; Narcolepsy; Sleep Apnea Syndromes; Sleep Wake Disorders
PubMed: 16522270
DOI: 10.1007/s11910-996-0039-2 -
Seminars in Neurology Sep 2009Hypersomnia is a frequently encountered symptom in clinical practice. The cardinal manifestation is inappropriate daytime sleepiness, common to all types of... (Review)
Review
Hypersomnia is a frequently encountered symptom in clinical practice. The cardinal manifestation is inappropriate daytime sleepiness, common to all types of hypersomnias. Hypersomnias of central origin are a rare cause of excessive daytime sleepiness, much rarer than the hypersomnia related to other pathologies, such as sleep-disordered breathing. Narcolepsy, with or without cataplexy, remains the most well studied of the primary hypersomnias. Although recognized more than a century ago, it was not until the end of the 20th century that major breakthroughs led to a better understanding of the disease, with hope of more specific therapies. The authors review the major aspects of this disorder, including the newer treatment modalities. Idiopathic hypersomnia is also part of the primary hypersomnias. Although difficult to diagnose, certain peculiarities stand out to help us differentiate it from the more commonly seen narcolepsy. The recurrent hypersomnias, particularly the Kleine-Levin syndrome, will be discussed. This rare disorder has been studied more closely in the last few years with abundant epidemiologic data assembled through literature and worldwide case reviews. Understanding the primary central hypersomnias warrants a thorough look from the original description, as well as a peek at the future, while more efficacious diagnostic and therapeutic interventions are currently being developed.
Topics: Cataplexy; Diagnosis, Differential; Disorders of Excessive Somnolence; Humans; Kleine-Levin Syndrome; Narcolepsy
PubMed: 19742411
DOI: 10.1055/s-0029-1237114