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Archives of Disease in Childhood Jan 2022Narcolepsy is a chronic disabling neurological sleep disorder that requires lifelong treatment. We have outlined the clinical features of narcolepsy, the assessment and... (Review)
Review
Narcolepsy is a chronic disabling neurological sleep disorder that requires lifelong treatment. We have outlined the clinical features of narcolepsy, the assessment and diagnosis process and have summarised the existing treatment options for children and adolescents with narcolepsy. In the future, the approach to management of paediatric narcolepsy should ideally be in a multidisciplinary setting, involving specialists in sleep medicine, sleep physiology, neurologists and psychologists/psychiatrists. A multidisciplinary approach will help to manage the potential impact of narcolepsy on children and adolescents who are in a stage of their life that is critical to their physical, emotional and social development and their academic attainment.
Topics: Actigraphy; Adolescent; Cataplexy; Central Nervous System Stimulants; Child; Exercise; Humans; Narcolepsy; Patient Care Team; Polysomnography; Sleep; Sleep Aids, Pharmaceutical; Wakefulness-Promoting Agents
PubMed: 33975822
DOI: 10.1136/archdischild-2020-320671 -
Current Opinion in Pulmonary Medicine Nov 2017Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development. (Review)
Review
PURPOSE OF REVIEW
Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development.
RECENT FINDINGS
Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Recent studies suggest both humoral and cellular immune responses in the disease development.
SUMMARY
Narcolepsy is a severe sleep disorder, in which neurons producing orexin/hypocretin in the hypothalamus are destroyed. The core symptoms of narcolepsy are debilitating, extreme sleepiness, cataplexy, and abnormalities in the structure of sleep. Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Importantly, the highest environmental risk is seen with influenza-A infection and immunization. However, how the cells are destroyed is currently unknown. In this review we summarize the disease symptoms, and focus on the immunological findings in narcolepsy. We also discuss the environmental and genetic risk factors as well as propose a model for disease development.
Topics: Autoimmunity; Genetic Predisposition to Disease; Humans; Immunity, Cellular; Immunity, Humoral; Influenza A virus; Influenza Vaccines; Influenza, Human; Narcolepsy; Risk Factors
PubMed: 28991006
DOI: 10.1097/MCP.0000000000000426 -
CMAJ : Canadian Medical Association... Jan 2024
Topics: Humans; Narcolepsy
PubMed: 38228341
DOI: 10.1503/cmaj.230650 -
Journal of Clinical Neurophysiology :... Jan 1990Narcolepsy is a neurological condition with a prevalence of up to 1 per 1,000 that is characterized by irresistible bouts of sleep. Associated features include the...
Narcolepsy is a neurological condition with a prevalence of up to 1 per 1,000 that is characterized by irresistible bouts of sleep. Associated features include the pathological manifestations of rapid-eye-movement (REM) sleep: cataplexy, sleep paralysis, hypnagogic hallucinations, and abnormal sleep-onset REM periods and disturbed nocturnal sleep. The condition is strongly associated with the HLA-DR2 and DQw1 phenotype. The phenomenology of narcolepsy is discussed, and diagnostic procedures are reviewed. Treatment modalities involving central nervous system stimulants for somnolence and tricyclic drugs for REM-sleep abnormalities are discussed. Sleep laboratory studies on the treatment efficacy of methylphenidate, pemoline, dextroamphetamine, protriptyline, and viloxazine are presented. Data suggest that: (1) methylphenidate and dextroamphetamine objectively improve somnolence; (2) pemoline, at doses up to 112.5 mg, is less effective in controlling somnolence but may improve certain aspects of performance; and (3) protriptyline and viloxazine are effective anticataplectic agents that produce little improvement in somnolence.
Topics: Adult; Antidepressive Agents; Central Nervous System Stimulants; Circadian Rhythm; Electroencephalography; Female; Humans; Male; Middle Aged; Narcolepsy; Pedigree; Sleep Stages
PubMed: 1968069
DOI: 10.1097/00004691-199001000-00008 -
Current Neuropharmacology 2022Sodium oxybate (SO) has been in use for many decades to treat narcolepsy with cataplexy. It functions as a weak GABAB agonist but also as an energy source for the brain...
Sodium oxybate (SO) has been in use for many decades to treat narcolepsy with cataplexy. It functions as a weak GABAB agonist but also as an energy source for the brain as a result of its metabolism to succinate and as a powerful antioxidant because of its capacity to induce the formation of NADPH. Its actions at thalamic GABAB receptors can induce slow-wave activity, while its actions at GABAB receptors on monoaminergic neurons can induce or delay REM sleep. By altering the balance between monoaminergic and cholinergic neuronal activity, SO uniquely can induce and prevent cataplexy. The formation of NADPH may enhance sleep's restorative process by accelerating the removal of the reactive oxygen species (ROS), which accumulate during wakefulness. SO improves alertness in normal subjects and in patients with narcolepsy. SO may allay severe psychological stress - an inflammatory state triggered by increased levels of ROS and characterized by cholinergic supersensitivity and monoaminergic deficiency. SO may be able to eliminate the inflammatory state and correct the cholinergic/ monoaminergic imbalance.
Topics: Cataplexy; Humans; Narcolepsy; Sleep; Sodium Oxybate; Wakefulness
PubMed: 33827411
DOI: 10.2174/1570159X19666210407151227 -
Journal of Clinical Sleep Medicine :... Oct 2020Mignot E, Black S. Narcolepsy risk and COVID-19. . 2020;16(10):1831–1833.
Mignot E, Black S. Narcolepsy risk and COVID-19. . 2020;16(10):1831–1833.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Narcolepsy; Pandemics; Pneumonia, Viral; SARS-CoV-2; Sleep
PubMed: 32621581
DOI: 10.5664/jcsm.8668 -
Journal of Clinical Sleep Medicine :... Jan 2022This review aimed to summarize current knowledge about disrupted nighttime sleep (DNS) and sleep instability in narcolepsy, including self-reported and objective... (Review)
Review
STUDY OBJECTIVES
This review aimed to summarize current knowledge about disrupted nighttime sleep (DNS) and sleep instability in narcolepsy, including self-reported and objective assessments, potential causes of sleep instability, health consequences and functional burden, and management.
METHODS
One hundred two peer-reviewed publications from a PubMed search were included.
RESULTS
DNS is a key symptom of narcolepsy but has received less attention than excessive daytime sleepiness and cataplexy. There has been a lack of clarity regarding the definition of DNS, as many sleep-related symptoms and conditions disrupt sleep quality in narcolepsy (eg, hallucinations, sleep paralysis, rapid eye movement sleep behavior disorder, nightmares, restless legs syndrome/periodic leg movements, nocturnal eating, sleep apnea, depression, anxiety). In addition, the intrinsic sleep instability of narcolepsy results in frequent spontaneous wakings and sleep stage transitions, contributing to DNS. Sleep instability likely emerges in the setting of orexin insufficiency/deficiency, but its exact pathophysiology remains unknown. DNS impairs quality of life among people with narcolepsy, and more research is needed to determine its contributions to cardiovascular risk. Multimodal treatment is appropriate for DNS management, including behavioral therapies, counseling on sleep hygiene, and/or medication. There is strong evidence showing improvement in self-reported sleep quality and objective sleep stability measures with sodium oxybate, but rigorous clinical trials with other pharmacotherapies are needed. Treatment may be complicated by comorbidities, concomitant medications, and mood disorders.
CONCLUSIONS
DNS is a common symptom of narcolepsy deserving consideration in clinical care and future research.
CITATION
Maski K, Mignot E, Plazzi G, Dauvilliers Y. Disrupted nighttime sleep and sleep instability in narcolepsy. . 2022;18(1):289-304.
Topics: Cataplexy; Humans; Narcolepsy; Quality of Life; Sleep; Sodium Oxybate
PubMed: 34463249
DOI: 10.5664/jcsm.9638 -
Journal of Internal Medicine May 2022The hypocretins (Hcrts), also known as orexins, are two neuropeptides produced exclusively in the lateral hypothalamus. They act on two specific receptors that are... (Review)
Review
The hypocretins (Hcrts), also known as orexins, are two neuropeptides produced exclusively in the lateral hypothalamus. They act on two specific receptors that are widely distributed across the brain and involved in a myriad of neurophysiological functions that include sleep, arousal, feeding, reward, fear, anxiety and cognition. Hcrt cell loss in humans leads to narcolepsy with cataplexy (narcolepsy type 1), a disorder characterized by intrusions of sleep into wakefulness, demonstrating that the Hcrt system is nonredundant and essential for sleep/wake stability. The causal link between Hcrts and arousal/wakefulness stabilisation has led to the development of a new class of drugs, Hcrt receptor antagonists to treat insomnia, based on the assumption that blocking orexin-induced arousal will facilitate sleep. This has been clinically validated: currently, two Hcrt receptor antagonists are approved to treat insomnia (suvorexant and lemborexant), with a New Drug Application recently submitted to the US Food and Drug Administration for a third drug (daridorexant). Other therapeutic applications under investigation include reduction of cravings in substance-use disorders and prevention of neurodegenerative disorders such as Alzheimer's disease, given the apparent bidirectional relationship between poor sleep and worsening of the disease. Circuit neuroscience findings suggest that the Hcrt system is a hub that integrates diverse inputs modulating arousal (e.g., circadian rhythms, metabolic status, positive and negative emotions) and conveys this information to multiple output regions. This neuronal architecture explains the wealth of physiological functions associated with Hcrts and highlights the potential of the Hcrt system as a therapeutic target for a number of disorders. We discuss present and future possible applications of drugs targeting the Hcrt system for the treatment of circuit-related neuropsychiatric and neurodegenerative conditions.
Topics: Humans; Intracellular Signaling Peptides and Proteins; Narcolepsy; Neuropeptides; Orexins; Sleep Initiation and Maintenance Disorders
PubMed: 35043499
DOI: 10.1111/joim.13406 -
Behavioral and Brain Functions : BBF Dec 2018Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. This disease affects... (Review)
Review
Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. This disease affects significantly the overall patient functioning, interfering with social, work, and affective life. Some symptoms of narcolepsy depend on emotional stimuli; for instance, cataplectic attacks can be triggered by emotional inputs such as laughing, joking, a pleasant surprise, and also anger. Neurophysiological and neurochemical findings suggest the involvement of emotional brain circuits in the physiopathology of cataplexy, which seems to depending on the dysfunctional interplay between the hypothalamus and the amygdala associated with an alteration of hypocretin levels. Furthermore, behavioral studies suggest an impairment of emotions processing in narcolepsy-cataplexy (NC), like a probable coping strategy to avoid or reduce the frequency of cataplexy attacks. Consistently, NC patients seem to use coping strategies even during their sleep, avoiding unpleasant mental sleep activity through lucid dreaming. Interestingly, NC patients, even during sleep, have a different emotional experience than healthy subjects, with more vivid, bizarre, and frightening dreams. Notwithstanding this evidence, the relationship between emotion and narcolepsy is poorly investigated. This review aims to provide a synthesis of behavioral, neurophysiological, and neurochemical evidence to discuss the complex relationship between NC and emotional experience and to direct future research.
Topics: Cataplexy; Emotions; Humans; Narcolepsy; Polysomnography; Sleep, REM
PubMed: 30587203
DOI: 10.1186/s12993-018-0151-x -
Human Vaccines & Immunotherapeutics 2016A link between Pandemrix™ (AS03-adjuvanted H1N1 pandemic influenza vaccine, GSK Vaccines, Belgium) and narcolepsy was first suspected in 2010 in Sweden and Finland... (Review)
Review
A link between Pandemrix™ (AS03-adjuvanted H1N1 pandemic influenza vaccine, GSK Vaccines, Belgium) and narcolepsy was first suspected in 2010 in Sweden and Finland following a number of reports in children and adolescents. Initial scepticism about the reported association faded as additional countries reported similar findings, leading several regulatory authorities to restrict the use of Pandemrix™. The authors acknowledge that currently available data suggest an increased risk of narcolepsy following vaccination with Pandemrix™; however, from an epidemiologist's perspective, significant methodological limitations of the studies have not been fully addressed and raise questions about the reported risk estimates. We review the most important biases and confounders that potentially occurred in 12 European studies of the observed association between Pandemrix™ and narcolepsy, and call for further analyses and debate.
Topics: Epidemiologic Methods; Europe; Humans; Influenza Vaccines; Narcolepsy
PubMed: 26379011
DOI: 10.1080/21645515.2015.1068486