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Narcolepsy is a primary neurological sleep disorder characterized by excessive daytime sleepiness, and in a majority of patients, cataplexy, which is sudden muscle weakness brought on by strong emotion. While often thought of as an adult condition, narcolepsy can be present at any age and may occur as often as 1 in 2000 individuals. Regardless of age, its effects are far-reaching, resulting in missed school or work days, poor school or work performance and all associated ramifications. In children and young-adults, narcolepsy can masquerade for years as anxiety, depression, attention deficit disorder and even bipolar disorder, thus delaying diagnosis. Most patients diagnosed with narcolepsy receive significant benefit from standard medication. In addition to medication, however, this article describes promising roles for clinical hypnosis in the care of young patients with narcolepsy, including through teaching them how to have more control over their sleepiness and the emotions that can induce cataplexy, while minimizing side effects that can occur when using narcolepsy medication.

Study Objectives: Mindfulness-based interventions (MBI) have been shown to improve psychosocial functioning in medical populations but have not been studied in narcolepsy. This study examined the feasibility and acceptability of an MBI that was adapted for narcolepsy, including three variations in program length., Methods: Adults with narcolepsy (N = 60) were randomized to MBI groups of varying durations: brief (4 weeks), standard (8 weeks), or extended (12 weeks). Participants completed assessments at baseline, 4, 8, and 12 weeks. To assess feasibility and acceptability, primary outcomes included attendance, meditation practice, and data completeness. Additionally, participants completed measures of mindfulness, self-compassion, mood, sleep, psychosocial functioning, and cognition. An effect size of Cohen's d ≥ 0.5 was used as the prespecified benchmark for a minimal clinically important difference (MCID)., Results: The attendance, meditation, and data completeness benchmarks were met by 71.7%, 61.7%, and 78.3% of participants, respectively. Higher proportions of the brief and extended groups met these benchmarks compared to the standard group. All groups met the MCID for mindfulness, self-compassion, self-efficacy for managing emotions, positive psychosocial impact, global mental health, and fatigue. Standard and extended groups met the MCID for anxiety and depression, and extended groups met the MCID for additional measures including social and cognitive functioning, daytime sleepiness, hypersomnia symptoms, and hypersomnia-related functioning., Conclusions: Results suggest that the remote delivery and data collection methods are feasible to employ in future clinical trials, and it appears that the extended MBI provides the most favorable clinical impact while maintaining attendance and engagement in meditation practice., Clinical Trial Registration: Awareness and Self-Compassion Enhancing Narcolepsy Treatment (ASCENT), NCT04306952, https://clinicaltrials.gov/ct2/show/NCT04306952., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Study Objectives: The purpose of this study was to characterize the incidence of pediatric narcolepsy diagnosis, subsequent care, and potential sociodemographic disparities in a large US claims database., Methods: Merative MarketScan insurance claims (n = 12,394,902) were used to identify youth (6-17 years of age) newly diagnosed with narcolepsy ( International Classification of Diseases, 10th revision codes). Narcolepsy diagnosis and care 1 year postdiagnosis included polysomnography with Multiple Sleep Latency Test, pharmacological care, and clinical visits. Potential disparities were examined by insurance coverage and child race and ethnicity (Medicaid-insured only)., Results: The incidence of narcolepsy diagnosis was 10:100,000, primarily type 2 (69.9%). Most diagnoses occurred in adolescents with no sex differences, but higher rates in Black vs White youth with Medicaid. Two thirds had a prior sleep disorder diagnosis and 21-36% had other co-occurring diagnoses. Only half (46.6%) had polysomnography with Multiple Sleep Latency Test (± 1 year postdiagnosis). Specialty care (18.9% pulmonary, 26.9% neurology) and behavioral health visits were rare (34.4%), although half were prescribed stimulant medications (51.0%). Medicaid-insured were 86% less likely than commercially insured youth to have any clinical care and 33% less likely to have polysomnography with Multiple Sleep Latency Test., Conclusions: Narcolepsy diagnoses occurred in 0.01% of youth, primarily during adolescence, and at higher rates for Black vs White children with Medicaid. Only half overall had evidence of a diagnostically required polysomnography with Multiple Sleep Latency Test, underscoring potential misdiagnosis. Many patients had co-occurring conditions, but specialty and behavioral health care were limited. Results suggest misdiagnosis, underdiagnosis, and limited narcolepsy treatment, as well as possible disparities. Results highlight the need to identify determinants of evidence-based pediatric narcolepsy diagnosis and management., Citation: Tang SH, Min J, Zhang X, et al. Incidence of pediatric narcolepsy diagnosis and management: evidence from claims data. J Clin Sleep Med . 2024;20(7):1141-1151., (© 2024 American Academy of Sleep Medicine.)

Background and Objective: No study on neurostimulation in narcolepsy is available until now. Arousal- and wake-promoting effects of vagus nerve stimulation (VNS) have been demonstrated in animal experiments and are well-known as side effects of VNS therapy in epilepsy and depression. The objective was to evaluate the therapeutic effect of VNS on daily sleepiness and cataplexies in narcolepsy., Methods: In our open-label prospective comparative study, we included narcolepsy patients who were treated with VNS because of depression or epilepsy and compared them to controls without narcolepsy treated with VNS for depression or epilepsy (18 patients in each group, aged 31.5 ± 8.2 years). We evaluated daily sleepiness (Epworth Sleepiness Scale, ESS) and the number of cataplexies per week before the implantation of VNS and at three and six month follow-ups., Results: Compared to baseline (ESS: 15.9 ± 2.5) patients with narcolepsy showed a significant improvement on ESS after three months (11.2 ± 3.3, p < 0.05) and six months (9.6 ± 2.8, p < 0.001) and a trend to reduction of cataplexies. No significant ESS-improvement was observed in patients without narcolepsy (14.9 ± 3.9, 13.6 ± 3.7, 13.2 ± 3.5, p = 0.2 at baseline, three and six months, correspondingly). Side effects did not differ between the study groups., Conclusion: In this first evaluation of VNS in narcolepsy, we found a significant improvement of daily sleepiness due to this type of neurostimulation. VNS could be a promising non-medical treatment in narcolepsy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:YW reports honoraria for educational presentations and consultations from Angelini Pharma, Arvelle Therapeutics, Bayer AG, BIAL, Bioprojet, Eisai, Idorsia Pharmaceuticals, JAZZ Pharmaceuticals, LivaNova, Novartis and UCB Pharma. SG received compensation for professional services from Abbott, Abbvie, Bial, Medtronic, UCB and Zambon; research grants from Abbott, Boston Scientific, MagVenture, German Research Council and German Ministry of Education and Health. MG received honoraria and educational grants from Precisis, LivaNova, Abbott, Medtronic, Boston Scientific and Nevro. CB, KS, DC, AZ, AK and AS declare no conflict of interest. JK performed consultations for Medtronic and Boston Scientific. FR is a consultant for Stryker, Brainlab, Icotec and Spineart and receives royalties from Spineart., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

While sleepiness is common among children, and particularly adolescents, profound sleepiness in the setting of apparently adequate sleep should prompt consideration of a central disorder of hypersomnolence. These disorders, which include narcolepsy, idiopathic hypersomnia, Kleine-Levin syndrome, and others, are likely underrecognized in the pediatric population. Narcolepsy in particular should be of interest to child neurologists as the unique signs and symptoms of this disease often prompt evaluation in pediatric neurology clinics. While sleepiness may appear to be a straightforward complaint, its evaluation requires a nuanced approach. Cataplexy, a hallmark of narcolepsy, can be confused for other neurologic conditions, though understanding its various manifestations makes it readily identifiable. Clinicians should be aware of these symptoms, as delay in diagnosis and misdiagnosis are common in childhood narcolepsy. While treatment options have been limited in the past, many new therapeutic options have become available and can result in significant improvement in symptoms. Given the age at presentation, paroxysmal and chronic features, diagnostic modalities, and available treatment options, the field of child neurology is well equipped to see patients with narcolepsy. In this review, I will focus on the presentation, evaluation, and management of pediatric patients with narcolepsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

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., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: This article provides a comprehensive review of pediatric sleep disorders including the clinical features, diagnosis, and treatment of sleep-disordered breathing, insomnia, parasomnias, restless sleep disorder, restless legs syndrome, narcolepsy in childhood, and Kleine-Levin syndrome., Latest Developments: Our understanding of pediatric sleep pathophysiology continues to evolve, and diagnostic and treatment modalities have expanded. A low-sodium oxybate formulation was approved in July 2020 in the United States to treat cataplexy and excessive daytime sleepiness in patients 7 years old and older with narcolepsy. A validated pediatric hypersomnolence survey for pediatric narcolepsy and idiopathic hypersomnia with high sensitivity, specificity, and interrater reliability is now available., Essential Points: The clinical presentation, diagnostics, and treatment of children with sleep disorders differ from those of adults. Untreated sleep disorders in childhood can lead to adverse physical and psychological consequences in adults. Correctly diagnosing and treating sleep disorders in youth can prevent a significant burden of disease in adulthood., (Copyright © 2023 American Academy of Neurology.)

Background and Objective: Excessive daytime sleepiness (EDS) has been far back reported as the most disabling symptom in the pediatric narcoleptic patients. However, there is a lack of studies to examine the circadian rhythms of EDS in pediatric narcoleptic population. Therefore, we aim to investigate the circadian rhythm of EDS in pediatric narcolepsy patients., Methods: We identified 50 pediatric narcoleptic patients (36 males and 14 females, mean age 13.68 ± 2.75 years). Data were collected through interviews and the relevant questionnaires (children depression inventory [CDI] and the pediatric quality of life inventory [PedsQL])., Result: The frequencies of sleep attacks during different intervals of the day differed significantly, with higher frequency in the morning (p < .001). The times of sleep attacks in the morning and in the afternoon were significantly associated with the degree of impairment on class and the severity of worry about sleepiness, with spearman correlation coefficient ranging from .289 to .496 (p < .05). The total scores of PedsQL and CDI differed significantly among morning sleepiness dominant, afternoon sleepiness dominant, and evening sleepiness dominant groups (p = .042, p = .040). The severity scores of the narcoleptic patients' sleepiness had two peaks, one of which occurred at 16:00, and the other peaks occurred at about 11:00., Conclusion: These results suggest that changes based on the circadian rhythm of sleepiness of the pediatric narcoleptic patients should be made in the treatment strategy. In addition, regulating the secretion of melatonin could serve as a promising treatment to relieve sleepiness in the future., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

This White Paper addresses the current gaps in knowledge, as well as opportunities for future studies in pediatric sleep. The Sleep Research Society's Pipeline Development Committee assembled a panel of experts tasked to provide information to those interested in learning more about the field of pediatric sleep, including trainees. We cover the scope of pediatric sleep, including epidemiological studies and the development of sleep and circadian rhythms in early childhood and adolescence. Additionally, we discuss current knowledge of insufficient sleep and circadian disruption, addressing the neuropsychological impact (affective functioning) and cardiometabolic consequences. A significant portion of this White Paper explores pediatric sleep disorders (including circadian rhythm disorders, insomnia, restless leg and periodic limb movement disorder, narcolepsy, and sleep apnea), as well as sleep and neurodevelopment disorders (e.g. autism and attention deficit hyperactivity disorder). Finally, we end with a discussion on sleep and public health policy. Although we have made strides in our knowledge of pediatric sleep, it is imperative that we address the gaps to the best of our knowledge and the pitfalls of our methodologies. For example, more work needs to be done to assess pediatric sleep using objective methodologies (i.e. actigraphy and polysomnography), to explore sleep disparities, to improve accessibility to evidence-based treatments, and to identify potential risks and protective markers of disorders in children. Expanding trainee exposure to pediatric sleep and elucidating future directions for study will significantly improve the future of the field., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess problems faced by children with type 1 narcolepsy (NT1) at school and obtain insight into potential interventions for these problems., Methods: We recruited children and adolescents with NT1 from three Dutch sleep-wake centers. Children, parents, and teachers completed questionnaires about school functioning, interventions in the classroom, global functioning (DISABKIDS), and depressive symptoms (CDI)., Results: Eighteen children (7-12 years) and thirty-seven adolescents (13-19 years) with NT1 were recruited. Teachers' most frequently reported school problems were concentration problems and fatigue (reported by about 60% in both children and adolescents). The most common arrangements at school were, for children, discussing school excursions (68%) and taking a nap at school (50%) and, for adolescents, a place to nap at school (75%) and discussing school excursions (71%). Regular naps at home on the weekend (children 71% and adolescents 73%) were more common than regular naps at school (children 24% and adolescents 59%). Only a minority of individuals used other interventions. School support by specialized school workers was associated with significantly more classroom interventions (3.5 versus 1.0 in children and 5.2 versus 4.1 in adolescents) and napping at school, but not with better global functioning, lower depressive symptom levels, or napping during the weekends., Conclusions: Children with NT1 have various problems at school, even after medical treatment. Interventions to help children with NT1 within the classroom do not seem to be fully implemented. School support was associated with the higher implementation of these interventions. Longitudinal studies are warranted to examine how interventions can be better implemented within the school.

Purpose: The aim of this review is to give updated information to pediatric neurologists on the correct diagnostic approach and treatment of excessive daytime sleepiness (EDS) in children and adolescents. Due to the change in the society habits, EDS is becoming an emerging problem for the health system. At the present there are few articles specifically devoted to the evaluation of EDS. EDS is often reported in several manuscripts as a side effect of other sleep disorders (obstructive sleep apnea, circadian disorders, etc.) or of the use of drugs or of the substance abuse or as a consequence of bad sleep habits and poor sleep hygiene. EDS, especially in children, may manifest with paradoxical symptoms like hyperactivity, inattention, and impulsiveness. However, common sign of EDS in children are the propensity to sleep longer than usual, the difficulty waking up in the morning, and falling asleep frequently during the day in monotonous situation. The diagnosis should include subjective (sleep diaries, questionnaires) and objective (polysomnography, multiple sleep latency test, etc.) instruments to avoid misdiagnosis. Narcolepsy is the most studied central disorder of hypersomnolence, and it is a predominantly pediatric disease with a peak age of onset in prepuberty but the diagnosis is often delayed especially in mild forms. The early and correct treatment of narcolepsy and of other form of EDS is extremely important since late and inappropriate treatments can affect the psychosocial development of the children and adolescents., Competing Interests: Declaration of competing interest The author reports no conflicts of interest related to this manuscript., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Narcolepsy is a relatively rare brain disorder caused by the selective loss of orexin neurons. Narcolepsy is divided into Narcolepsy Type 1 (NT1) and Narcolepsis Type 2 (NT2). The pathogenesis of NT1 has been well established due to the severe loss of orexin neurons, while NT2 is still poorly understood, and little is known about its underlying neurobiological mechanisms. human leukocyte antigen alleles have been found to strongly influence the development of narcolepsy, with more than 90% of NT1 patients carrying the human leukocyte antigen II allele DQB1*06:02. In addition to the genetic evidence for the DQBI*06:02 allele, some other evidence suggests that a T cell-mediated immune mechanism destroys the orexin neurons of NT1, with CD4 + T cells being key. For this disease, traditional Chinese medicine (TCM) therapy has its own characteristics and advantages, especially the combination of acupuncture and medicine in the treatment of this disease in TCM, which has made considerable and gratifying progress. The purpose of this review is to introduce the frontier progress of neurobiology of narcolepsy, and to explore the syndrome differentiation and treatment of narcolepsy with the combined use of TCM and Western medicine combined with TCM., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Objectives: To systematically determine subjective and objective outcome measures used to measure the efficacy of narcolepsy interventions in randomized controlled trials (RCTs) in adults and children and assess psychometric properties of patient-reported outcome measures (PROMs) used., Methods: We searched bibliographical databases and clinical trial registries for narcolepsy RCTs and extracted objective and subjective outcome measures. If PROMs were used, we searched for psychometric studies conducted in a narcolepsy population using bibliographical databases and appraised using Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines., Results: In total, 80 different outcome measures were used across 100 RCTs. Epworth Sleepiness Scale (ESS) (n = 49) and Maintenance of Wakefulness Test (n = 47) were the most frequently used outcome measures. We found 19 validation studies of 10 PROMs in narcolepsy populations. There was limited evidence for validity or responsiveness of the ESS; yet sufficient reliability (pooled ICC: 0.81-0.87). Narcolepsy Severity Scale (NSS) had sufficient reliability (pooled ICC: 0.71-0.92) and both adult and pediatric versions had sufficient discriminant validity (treated/untreated). Content validity was only evaluated in pediatric populations for ESS-CHAD and NSS-P and rated inconclusive. Quality of evidence of the psychometric studies for all scales ranged from very low to low., Conclusions: Although recognized by regulatory bodies and widely used as primary outcome measures in trials, there is surprisingly little evidence for the validity, reliability, and responsiveness of PROMs frequently used to assess treatment efficacy in narcolepsy. The field needs to establish patient-centered minimal clinically important differences for the PROMs used in these trials., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society.)

This article addresses the clinical presentation, diagnosis, pathophysiology and management of narcolepsy type 1 and 2, with a focus on recent findings. A low level of hypocretin-1/orexin-A in the cerebrospinal fluid is sufficient to diagnose narcolepsy type 1, being a highly specific and sensitive biomarker, and the irreversible loss of hypocretin neurons is responsible for the main symptoms of the disease: sleepiness, cataplexy, sleep-related hallucinations and paralysis, and disrupted nocturnal sleep. The process responsible for the destruction of hypocretin neurons is highly suspected to be autoimmune, or dysimmune. Over the last two decades, remarkable progress has been made for the understanding of these mechanisms that were made possible with the development of new techniques. Conversely, narcolepsy type 2 is a less well-defined disorder, with a variable phenotype and evolution, and few reliable biomarkers discovered so far. There is a dearth of knowledge about this disorder, and its aetiology remains unclear and needs to be further explored. Treatment of narcolepsy is still nowadays only symptomatic, targeting sleepiness, cataplexy and disrupted nocturnal sleep. However, new psychostimulants have been recently developed, and the upcoming arrival of non-peptide hypocretin receptor-2 agonists should be a revolution in the management of this rare sleep disease, and maybe also for disorders beyond narcolepsy., (© 2022 European Sleep Research Society.)

Narcolepsy type 1 is a central disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy (i.e., sudden loss of muscle tone during wakefulness triggered by emotions), and REM sleep-related manifestations that can present with a peculiar phenotype when arising at a pediatric age. Several features of childhood-onset narcolepsy type 1 are also common in neuropsychiatric conditions; discrete neuropsychiatric comorbidity has also been demonstrated. Here, we report on 3 children with very early narcolepsy type 1. All 3 patients had psychiatric features at the time of symptom onset coupled with peculiar motor disturbances. The course of narcolepsy symptoms also paralleled neuropsychiatric symptoms, suggesting a possible intrinsic link between sleep and psychological features. Multidisciplinary management is mandatory for pediatric narcolepsy type 1 since prompt disease management addressing neuropsychiatric symptoms could lead to better clinical outcomes and quality of life., (© 2022 American Academy of Neurology.)

Study Objectives: Previous estimated prevalence of narcolepsy in Europe was 47 patients per 100,000 persons, with a yearly incidence of 0.64-1.37 per 100,000. However, analyses of representative datasets from large cohorts are limited. This study aimed to estimate the population-based diagnostic prevalence and incidence of narcolepsy in Germany and to describe these patients and their health care resource utilization., Methods: This study used the InGef research database, an anonymized representative dataset of 4 million persons covered by statutory health insurance in Germany. Patients with confirmed narcolepsy diagnoses in 2018 were included. Mid-p-exact tests were used to calculate 95% confidence intervals. Patients with narcolepsy diagnoses and narcolepsy-targeting therapy in 2014-2018 were included to describe health care resource utilization in the year prior to diagnosis., Results: In 2018, diagnostic prevalence was estimated as 17.88 (95% confidence interval 16.45-19.40) and 12-month incidence as 0.79 (0.52-1.15) per 100,000 persons. Forty-six percent of patients were in psycho-behavioral therapeutic treatment and 61% of employees had sick leave days. One in three patients was hospitalized for any cause; 28% received antibiotics., Conclusions: Diagnostic prevalence was lower, but incidence was consistent with previous reports, although previous estimates may diverge in terms of age/sex distributions. Patients showed a substantial utilization of health care resources, including sick leave and hospitalization. Almost half the patients underwent psycho-behavioral treatment in the year prior to diagnosis, which might indicate a high burden of psychiatric symptoms. The increased use of antibiotics could indicate more frequent infections than in the general population., Citation: Kallweit U, Nilius G, Trümper D, Vogelmann T, Schubert T. Prevalence, incidence, and health care utilization of patients with narcolepsy: a population-representative study. J Clin Sleep Med . 2022;18(6):1531-1537., (© 2022 American Academy of Sleep Medicine.)

Background and Objectives: Narcolepsy and idiopathic hypersomnia usually begin in early adolescence, but diagnostic delays ranging from 5 to 10 years are common, affecting disease burden. To improve early identification of these treatable conditions, we developed and validated the Pediatric Hypersomnolence Survey (PHS)., Methods: Content was developed through literature review, patient focus groups, interviews with experts in the field, and field testing. We then validated the 14-item self-reported survey across 3 hospitals and web recruitment from patient groups. In the validation phase, we recruited a total of 331 participants (patients with narcolepsy type 1 [n = 64], narcolepsy type 2 [n = 34], idiopathic hypersomnia [n = 36], and other sleep disorders [n = 97] and healthy controls [n = 100], ages 8-18 years) to complete the survey. We assessed a range of psychometric properties, including discriminant diagnostic validity for CNS disorders of hypersomnolence using receiver operating characteristic curve analysis and reliability across a 1-week period., Results: Confirmatory factor analysis indicated a 4-domain solution with good reliability expressed by satisfactory omega values. Across groups, the PHS total score showed appropriate positive correlations with other validated surveys of sleepiness ( r = 0.65-0.78, p < 0.001) and negative correlations with multiple sleep latency test measures (mean sleep latency: r = -0.27, p = 0.006; number of sleep-onset REM periods: r = 0.26, p = 0.007). Compared to controls and patients with other sleep disorders, the area under the curve for participants with narcolepsy or idiopathic hypersomnia was 0.87 (standard error 0.02, 95% CI 0.83-0.91) with high sensitivity (81.3, 95% CI 73.7%-87.5%) and specificity (81.2%, 95 CI 75.1%-86.4%). Test-retest reliability was r = 0.87., Discussion: The PHS is a valid and reliable tool for clinicians to identify pediatric patients with narcolepsy and idiopathic hypersomnia. Implemented in clinical practice, the PHS will potentially decrease diagnostic delays and time to treatment, ultimately reducing disease burden for these debilitating conditions., Classification of Evidence: This study provides Class III evidence that the PHS accurately identifies patients with central disorders of hypersomnolence., (© 2022 American Academy of Neurology.)

Sleep disorders are common in the general adult population and are associated with adverse effects such as motor vehicle collisions, decreased quality of life, and increased mortality. Patients with sleep disorders can be categorized into three groups: people with problems falling asleep, people with behavior and movement disturbances during sleep, and people with excessive daytime sleepiness. Insomnia, the most common sleep disorder, is defined by difficulty initiating sleep, maintaining sleep, or both, resulting in daytime consequences. Insomnia is diagnosed by history and is treated with cognitive behavior therapy, with or without medications. Rapid eye movement sleep behavior disorder is characterized by increased muscle tone during rapid eye movement sleep, resulting in patients acting out their dreams with potentially harmful effects. Rapid eye movement sleep behavior disorder is diagnosed by polysomnography and treated with melatonin or clonazepam. Restless legs syndrome is defined by an urge to move the legs that worsens when at rest. Restless legs syndrome is treated with gabapentin or dopamine agonists, depending on the severity. Narcolepsy is characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and sleep hallucinations. Diagnosis is suggested by the history and can be confirmed with polysomnography and a multiple sleep latency test the following day. Narcolepsy is treated with behavior modifications and medications such as stimulants, selective serotonin reuptake inhibitors, sodium oxybate, and pitolisant. Obstructive sleep apnea may be diagnosed in patients with excessive snoring and witnessed apneas and can be diagnosed using overnight polysomnography. Treatment consists of positive airway pressure therapy while sleeping in conjunction with weight loss.

It is unclear why orexin-deficient animals, but not wild-type mice, show cataplexy. The current hypothesis predicts simultaneous excitation of cataplexy-inhibiting orexin neurons and cataplexy-inducing amygdala neurons. To test this hypothesis, we measured the activity of putative orexin neurons in orexin-knockout mice during cataplexy episodes using fiber photometry. We created two animal models of orexin-knockout mice with a GCaMP6 fluorescent indicator expressed in putative orexin neurons. We first prepared orexin-knockout mice crossed with transgenic mice carrying a tetracycline-controlled transactivator transgene under the control of the orexin promoter. TetO-GCaMP6 was then introduced into mice via an adeno-associated virus injection or natural crossing. The resulting two models showed restricted expression of GCaMP6 in the hypothalamus, where orexin neurons should be located, and showed excitation to an intruder stress that was similar to that observed in orexin-intact mice in our previous study. The activity of these putative orexin neurons increased immediately before the onset of cataplexy-like behavior but decreased (approximately - 20% of the baseline) during the cataplexy-like episode. We propose that the activity of orexin neurons during cataplexy is moderately inhibited by an unknown mechanism. The absence of cataplexy in wild-type mice may be explained by basal or residual activity-induced orexin release, and emotional stimulus-induced counter activation of orexin neurons may not be necessary. This study will serve as a basis for better treatment of cataplexy in narcolepsy patients., (© 2022. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH., (© 2021 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Objective: We validated the Narcolepsy Severity Scale (NSS) in adults with narcolepsy type 1 (NT1) to quantify the severity, frequency, and consequences of the 5 key narcolepsy symptoms over the last month, and we now developed the Pediatric NSS (NSS-P); thus, the aims of this study were to assess NSS-P psychometric properties, validity, and reliability, and to evaluate its responsiveness to treatment in a well-characterized sample of children and adolescents with NT1., Methods: The NSS was reformulated for children, and the item about driving was removed. The total score of the 14-item NSS-P ranges from 0 to 54, and higher scores reflect more severe disease. Children and adolescents (n = 209, 6-17 years of age) with NT1 diagnosed in 2 Reference Centers for Narcolepsy in France were consecutively asked to fill in the NSS-P. The scale was fully and correctly completed by 160 (10-18 years of age, 68 untreated). Moreover, 65 participants completed it twice (33 before/during treatment, and 32 under the same treatment). The NSS-P psychometric properties, score changes before/during treatment, and convergent validity with other clinical parameters were assessed., Results: The NSS-P showed adequate psychometric properties with significant item-total score correlations. Factor analysis indicated a 4-factor solution with good reliability. The NSS-P score was lower in treated than untreated patients with a mean difference of 3.71 ± 1.45, with a minimum clinically important difference between untreated and treated patients in the longitudinal sample estimated at 4 points. Four severity levels were defined (mild, moderate, severe, very severe) with between-group differences related to treatment. The NSS-P total score was associated with self-reported sleepiness, insomnia, and depressive symptoms. Its temporal stability was satisfactory., Discussion: We validated a brief instrument to assess NT1 symptom frequency, severity, and consequences in ≥10-year-old children and adolescents with 4 clinically relevant severity score ranges. This scale constitutes a relevant tool to improve and provide guidance for NT1 management in pediatric populations. The ease of administration, its good psychometric properties, and its sensitivity to detect symptom changes after treatment ensure future use of the NSS-P in clinical and research settings., (© 2021 American Academy of Neurology.)

Abstract: Narcolepsy continues to be a significantly underdiagnosed/misdiagnosed condition worldwide. According to the National Institutes of Health (NIH), an estimated 135,000 to 200,000 patients in the United States are living with narcolepsy. However, due to the number of patients who either do not seek medical advice for their symptoms or receive an incorrect initial diagnosis at onset, this number may be higher. This article reviews the different subtypes of narcolepsy along with the pathophysiology, screening guidelines, clinical features, diagnosis, and management of the disorder. Educational awareness from a healthcare and patient standpoint can enhance early detection and accurate diagnosis of narcolepsy and improve patient quality of life., (Copyright © 2021 American Academy of Physician Assistants.)

Obstructive sleep apnea (OSA) has been shown to increase risk of adverse perioperative events. More recently, investigators have begun to examine other common sleep disorders to assess how they may be impacted by the perioperative environment, as well as influence postoperative outcomes. There are a number of mechanisms by which such common sleep disorders (eg, insomnia, restless legs syndrome, narcolepsy, and parasomnias) may have consequences in the perioperative setting, both related to the underlying pathophysiology of the diseases as well as their treatments. This review will highlight the current state of the literature and offer recommendations for management of these conditions during the perioperative journey., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

The cause of obesity in narcolepsy type 1 (NT1) patients is not fully understood. The present study investigated if a reduced physical activity could explain weight gain in NT1. Seventy-nine patients were included in this retrospective study and divided into an NT1 group (n = 56) and a non-NT1 group (n = 23), including NT2 and idiopathic hypersomnia (IH). Accelerometry-derived measures of physical activity, total energy expenditure and skin temperature were collected from patients during seven consecutive days without medication. In addition, results from multiple sleep latency tests and the Epworth Sleepiness Scale questionnaire, body weight, height and CSF orexin/hypocretin were acquired. Three measurements of physical activity, including metabolic equivalent of task (MET), the average time of physical activity and step count, were compared without differences between groups. Neither could we find a significant difference in total energy expenditure or skin temperature. Thus, by analysing accelerometric data, we could not find any differences in the amount of physical activity or total energy expenditure explaining overweight in NT1., (© 2020 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Narcolepsy is a hypersomnolence disorder of central origin that presents with a disturbance of the wake-sleep regulation. Lead symptoms consist of excessive daytime sleepiness and cataplexy. Nowadays, two types of narcolepsy are distinguished. Type 1 narcolepsy, formerly known as narcolepsy with cataplexy, is based on hypocretin deficiency. The cause of type 2 narcolepsy, formerly known as narcolepsy without cataplexy, remains mainly unknown. A multimodal approach is necessary for diagnosis. The mean latency between the onset of disease and diagnosis in Europe ranges 14 years. Narcolepsy has a major impact on workability and quality of life. The management of narcolepsy is usually life-long and includes non-pharmacological approaches and a symptomatic pharmacological treatment., Competing Interests: MPM erhielt Honorare für Vortrags- und Beratertätigkeit von UCB und EISAI.JN berichtet keine Interessenkonflikte.AT berichtet keine Interessenkonflikte.UK erhielt Honorare für Vortrags- und Beratertätigkeit von AOP Orphan Pharmaceuticals, Bioprojet Pharma, Harmony Biosciences, Jazz Pharma, Takeda Pharmaceutical, UCB Pharma. Die wissenschaftlichen Arbeiten wurden unterstützt durch das European Narcolepsy Network, die Universität Witten/Herdecke (interne Forschungsförderung Nr. 2020-31), Bioprojet Pharma, Harmony Biosciences und UCB Pharma., (Thieme. All rights reserved.)

Narcolepsy is a rare, chronic, and disabling central nervous system hypersomnia; two forms can be recognized: narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). Its etiology is still largely unknown, but studies have reported a strong association between NT1 and HLA, as well as a pathogenic association with the deficiency of cerebrospinal hypocretin-1. Thus, the most reliable pathogenic hypothesis is an autoimmune process destroying hypothalamic hypocretin-producing cells. A definitive cure for narcolepsy is not available to date, and although the research in the field is highly promising, up to now, current treatments have aimed to reduce the symptoms by means of different pharmacological approaches. Moreover, overall narcolepsy symptoms management can also benefit from non-pharmacological approaches such as cognitive behavioral therapies (CBTs) and psychosocial interventions to improve the patients' quality of life in both adult and pediatric-affected individuals as well as the well-being of their families. In this review, we summarize the available therapeutic options for narcolepsy, including the pharmacological, behavioral, and psychosocial interventions.

Study Objectives: Narcolepsy type 1 (NT1) is a chronic rare hypersomnia of central origin requiring a combination of behavioral and pharmacological treatments. During the coronavirus disease 2019 (COVID-19) pandemic, in Italy the population was forced into a lockdown. With this study, we aimed to describe the lockdown impact on NT1 symptom management, according to different patients' working schedule., Methods: In the period between 10 April and 15 May 2020, we performed routine follow-up visits by telephone (as recommended during the COVID-19 emergency) to 50 patients >18 years old (40% males) under stable long-term treatment. We divided patients into three groups: unchanged working schedule, forced working/studying at home, and those who lost their job ("lost occupation"). Current sleep-wake habit and symptom severity were compared with prelockdown assessment (six months before) in the three patient groups., Results: At assessment, 20, 22, and eight patients belonged to the unchanged, working/studying at home, and lost occupation groups, respectively. While in the lost occupation group, there were no significant differences compared with prepandemic assessment, the patients with unchanged schedules reported more nocturnal awakenings, and NT1 patients working/studying at home showed an extension of nocturnal sleep time, more frequent daytime napping, improvement of daytime sleepiness, and a significant increase in their body mass index. Sleep-related paralysis/hallucinations, automatic behaviors, cataplexy, and disturbed nocturnal sleep did not differ., Conclusions: Narcolepsy type 1 patients working/studying at home intensified behavioral interventions (increased nocturnal sleep time and daytime napping) and ameliorated daytime sleepiness despite presenting with a slight, but significant, increase of weight., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Narcolepsy Type 1 (NT1) is hypothesized to be an autoimmune disease targeting the hypocretin/orexin neurons in the lateral hypothalamus. Ample genetic and epidemiologic evidence point in the direction of a pathogenesis involving the immune system. Many autoantibodies have been detected in blood samples from NT1 patients, but none in a consistent manner. Importantly, T cells directed toward hypocretin/orexin neurons have been detected in samples from NT1 patients. However, it remains to be seen if these potentially autoreactive T cells are also present in the hypothalamus and if they are pathogenic. For this reason, NT1 does still not fully meet the criteria for being classified as a genuine autoimmune disease, even though more and more results are pointing in that direction as will be described in this chapter. The autoimmune hypothesis has led to many attempts at slowing or stopping disease progression with immunomodulatory treatment, but so far the overall results have not been very encouraging. It is clear that more research into the pathogenesis of NT1 is needed to establish the precise role of the immune system in disease development., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Narcolepsy type 1 (NT1, narcolepsy with cataplexy) is a disabling neurological disorder caused by loss of excitatory orexin neurons from the hypothalamus and is characterized by decreased motivation, sleep-wake fragmentation, intrusion of rapid-eye-movement sleep (REMS) during wake, and abrupt loss of muscle tone, called cataplexy, in response to sudden emotions., Objective: We investigated whether subcortical stimulation, analogous to clinical deep brain stimulation (DBS), would ameliorate NT1 using a validated transgenic mouse model with postnatal orexin neuron degeneration., Methods: Using implanted electrodes in freely behaving mice, the immediate and prolonged effects of DBS were determined upon behavior using continuous video-electroencephalogram-electromyogram (video/EEG/EMG) and locomotor activity, and neural activation in brain sections, using immunohistochemical labeling of the immediate early gene product c-Fos., Results: Brief 10-s stimulation to the region of the lateral hypothalamus and zona incerta (LH/ZI) dose-responsively reversed established sleep and cataplexy episodes without negative sequelae. Continuous 3-h stimulation increased ambulation, improved sleep-wake consolidation, and ameliorated cataplexy. Brain c-Fos from mice sacrificed after 90 min of DBS revealed dose-responsive neural activation within wake-active nuclei of the basal forebrain, hypothalamus, thalamus, and ventral midbrain., Conclusion: Acute and continuous LH/ZI DBS enhanced behavioral state control in a mouse model of NT1, supporting the feasibility of clinical DBS for NT1 and other sleep-wake disorders., Competing Interests: Declaration of competing interest JTW serves as a consultant to Medtronic, Inc., Neuropace, Inc., and MRI Interventions, Inc., and receives compensation for these services, which are not directly related to this study. The terms of these arrangements have been received and approved by Emory University in accordance with its conflict of interest policies. The remaining authors have nothing to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Orexin is a neurotransmitter that mainly regulates sleep/wake cycle. In addition to its sleep cycle regulatory role, it is involved in regulation of attention, energy homeostasis, neurogenesis and cognition. Several evidences has shown the involvement of orexin in narcolepsy, but there are also growing evidences that shows the disturbance in orexin system in neurodegenerative diseases including Alzheimer's, Parkinson's, Epilepsy, Huntington's diseases and Amyotrophic lateral sclerosis. Pathogenesis and clinical symptoms of these disorders can be partly attributed from orexin system imbalance. However, there are controversial reports on the exact relationship between orexin and these neurodegenerative diseases. Therefore, the aim of this review is to summarize the current evidences regarding the role of orexin in these neurodegenerative diseases., Competing Interests: Declaration of competing interest We, the authors, declare that the research was conducted in the absence of any potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Excessive daytime sleepiness (EDS) is the core complaint of central nervous system (CNS) hypersomnias. In this mini-review, we summarized EDS features in CNS hypersomnias to provide a guide for differential diagnosis purposes., Methods: A review of recent literature was performed to provide an update in CNS hypersomnias., Results: At clinical evaluation, narcolepsy patients report a good restorative potential of sleep together with the frequent occurrence of dreaming even during short-lasting naps. These features are mirrored by the neurophysiological evidence of REM sleep at sleep onset (SOREMP) during the Multiple Sleep Latency Test (MSLT), a specific marker. Conversely, patients with idiopathic hypersomnia (IH) complain sleep inertia and prolonged nocturnal sleep. Polysomnographic studies show high sleep propensity on the MSLT or high 24-h total sleep time during continuous monitoring. Patients with insufficient sleep syndrome (ISS) can present with variable clinical EDS features in between narcolepsy and IH. ISS diagnosis is based on the clinical evidence of nocturnal sleep curtailment (weekdays versus vacations) associated with the disappearance of EDS complaint after sleep extension. Polysomnographic data are not required, but when the MSLT is performed, ISS patients can present with SOREMP arising from non-REM stage 2 sleep (vs narcolepsy patients entering into SOREM most frequently from wakefulness). Kleine-Levin Syndrome is characterized by recurrent episodes of enormously prolonged sleep time lasting days associated with abnormal cognition and behavior intermixed by asymptomatic periods, a sleep pattern that can be well documented by actigraphy., Conclusions: Different CNS hypersomnias present with specific features of EDS are useful to guide the clinician to apply and interpret appropriate neurophysiological investigations.

Unlike other reviews written on this topic, the focus of this article is primarily on nonpharmacologic treatments for daytime sleepiness that is not secondary to other medical or psychological conditions. To provide an appropriate background on primary excessive daytime sleepiness, what is considered optimal sleep in terms of sleep duration, sleep insufficiency, and sleep need is discussed in detail. This discussion is followed by an examination of the behavioral strategy of banking sleep. After briefly discussing behavioral interventions for sleepiness associated with narcolepsy, a new behavioral method of treating daytime somnolence is proposed and described., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Narcolepsy is a disabling, rare, and chronic sleep disorder, currently classified as distinct central nervous system hypersomnia in narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). Although today a reliable pathogenic hypothesis identifies the cause of NT1 as an autoimmune process destroying hypocretin-producing cells, there is no cure for narcolepsy, and the symptomatic pharmacological available treatments are not entirely effective for all symptoms. Behavioral therapies play a synergistic role in the disease treatment. We here review the available therapeutic options for narcolepsy, including symptomatic pharmacological treatments as well as behavioral and psychosocial interventions that could help clinicians improve the quality of life of patients with narcolepsy in adulthood and childhood.

Background: Narcolepsy is a rare chronic sleep disorder that typically begins in youth. Excessive daytime sleepiness is the main disabling symptom, but the disease is often associated with severe endocrine-metabolic and psychosocial issues, worsened by a long diagnostic delay, requiring a multidisciplinary approach. The scarcity of reference Sleep Centres forces the patient and family to travel for seeking medical consultations, increasing the economic and psychosocial burden of the disease. Growing evidence suggests that Telemedicine may facilitate patient access to sleep consultations and its non-inferiority in terms of patient satisfaction, adherence to treatment, and symptom improvement for sleep disorders. However, Telemedicine clinical and economic benefits for patients with narcolepsy are still unknown., Methods: TENAR is a two-part project, including: 1. a cross-sectional study (involving 250 children and adults with suspected narcolepsy) evaluating the accuracy of Teletriage (i.e., a synchronous live interactive sleep assessment through a Televisit) for narcolepsy diagnosis compared to the reference standard; and 2. a two-arm, parallel, open randomized controlled trial (RCT) to demonstrate the non-inferiority of the multidisciplinary care of narcolepsy through Televisits versus standard care. In this RCT, 202 adolescents (> 14 y.o.) and adults with narcolepsy will be randomly allocated (1:1 ratio) either to Televisits via videoconference or to standard in-person outpatient follow-up visits (control arm). The primary outcome is sleepiness control (according to the Epworth Sleepiness Scale). Secondary outcomes are other symptoms control, compliance with treatment, metabolic control, quality of life, feasibility, patient and family satisfaction with care, safety, and disease-related costs. At baseline and at 12 months, patients will undergo neurologic, metabolic, and psychosocial assessments and we will measure primary and secondary outcomes. Primary outcomes will be also measured at 6 months (remotely or in person, according to the arm)., Discussion: TENAR project will assess, for the first time, the feasibility, accuracy, efficacy and safety of Telemedicine procedures applied to the diagnosis and the multidisciplinary care of children and adults with narcolepsy. The study may be a model for the remote management of other rare disorders, offering care access for patients living in areas lacking medical centres with specific expertise., Trial Registration: Number of the Tele-multidisciplinary care study NCT04316286. Registered 20 March 2020.

Purpose: This review (Part II of a series on sleep disorders) presents an update of the characteristics, epidemiology, assessment, and latest management of insomnia, restless legs syndrome (Willis-Ekbom disease; RLS/WED), and narcolepsy. Insomnia, the most common sleep disorder and most prevalent of all psychological health disorders, is a problem of difficulty initiating and maintaining sleep and early morning awakenings. RLS/WED is characterized by a crawling sensation or urge to move the legs in the evening and nighttime. Narcolepsy is a sleep disorder that commonly results in chronic daytime sleepiness and cataplexy. Nonpharmacological management, which includes education, cognitive behavioral therapy, and complementary therapy, is used as primary or adjunctive to pharmacotherapy for the treatment of these disorders., Methods: This narrative review utilized medical databases such as PubMed to identify relevant English-language original and systematic review articles predominantly from peer-reviewed journals from 2012 to 2019. However, as background, findings from classic articles prior to 2012 were also included., Clinical Relevance: Assessment of sleep problems, excessive sleepiness, and difficulty performing activities or being productive should be routine in the care of all patients. Utilization of behavioral interventions, including cognitive behavioral therapy, in addition to education and sleep hygiene, can promote sleep quality. Management of insomnia, RLS/WED, and narcolepsy should include helping patients adjust to treatment, managing cataplexy triggers in narcolepsy, and initiating strategies to live with chronic illness to improve quality of life., (© 2019 Sigma Theta Tau International.)

Background: Patients with narcolepsy may be at increased perioperative risk due to the interactions among anesthesia, narcolepsy, and narcolepsy medications. This study sought to determine the perioperative experience of narcoleptic patients undergoing anesthesia or sedation, the frequency of perioperative counseling, and self-reported surgical complications., Methods: A 22-question survey was developed by expert consensus and distributed by the Narcolepsy Network. Recruitment was via the Narcolepsy Network's list-serve and a Facebook link to the survey. One thousand and twenty respondents reported a diagnosis of narcolepsy and 1 or more procedures under anesthesia or sedation. Descriptive, comparative statistics and logistic regression were utilized., Results: Respondents were mostly women (79.5%) and Caucasian (84.9%), with a mean age of 45 ± 16 years. Most respondents did not receive counseling regarding the possibility of increased sleepiness (70%), cataplexy (90%), or drowsy driving (59%) postanesthesia. More than half of respondents reported adverse events (medication withdrawal symptoms, inadequate pain relief, increased cataplexy). Subjects with cataplexy more frequently reported surgical complications (70% vs 31%; P = .03) and medication withdrawal symptoms (stimulant medications: odds ratio, 3.0 [95% CI, 1.9, 3.06]; P > .001 and antidepressant medications: odds ratio, 6.5 [95% CI, 2.1-19.5]; P = .001). Of the total sample, 18% indicated surgical complications. Undergoing 5 or more separate surgeries or procedures was associated with a 2-fold increase in self-reported complications (odds ratio, 2.2 [95% CI, 1.3-3.4]; P = .001), difficulty waking (odds ratio, 2.1 [95% CI, 1.45-3.06]; P = .001), and inadequate pain relief (odds ratio, 1.77 [95% CI, 1.01-3.13]; P < .05)., Conclusions: Most narcoleptic patients report not receiving counseling regarding potential worsening of narcolepsy symptoms postanesthesia or an increased risk of drowsy driving. Enhanced education of perioperative providers about potential narcolepsy-related issues is essential. Respondents frequently self-report adverse events in the perioperative period. Future studies should clarify the perioperative risk associated with narcolepsy to optimize the care and safety of narcoleptic patients.

Narcolepsy is a rare brain disorder that reflects a selective loss or dysfunction of orexin (also known as hypocretin) neurons of the lateral hypothalamus. Narcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy, accompanied by sleep-wake symptoms, such as hallucinations, sleep paralysis and disturbed sleep. Diagnosis is based on these clinical features and supported by biomarkers: evidence of rapid eye movement sleep periods soon after sleep onset; cerebrospinal fluid orexin deficiency; and positivity for HLA-DQB1*06:02. Symptomatic treatment with stimulant and anticataplectic drugs is usually efficacious. This Review focuses on our current understanding of how genetic, environmental and immune-related factors contribute to a prominent (but not isolated) orexin signalling deficiency in patients with NT1. Data supporting the view of NT1 as a hypothalamic disorder affecting not only sleep-wake but also motor, psychiatric, emotional, cognitive, metabolic and autonomic functions are presented, along with uncertainties concerning the 'narcoleptic borderland', including narcolepsy type 2 (NT2). The limitations of current diagnostic criteria for narcolepsy are discussed, and a possible new classification system incorporating the borderland conditions is presented. Finally, advances and obstacles in the symptomatic and causal treatment of narcolepsy are reviewed.

Objective: To validate the Idiopathic Hypersomnia Severity Scale (IIHSS), a self-report measure of hypersomnolence symptoms, consequences, and responsiveness to treatment., Methods: The 14-item IHSS (developed and validated by sleep experts with patients' feedback) was filled in by 218 participants (2.3% missing data). Among the 210 participants who fully completed the IHSS, there were 57 untreated and 43 treated patients with idiopathic hypersomnia (IH) aged 16 years or older, 37 untreated patients with narcolepsy type 1 (NT1), and 73 controls without sleepiness. IHSS psychometric properties, discriminant diagnostic validity, and score changes with treatment were assessed., Results: The IHSS showed good internal consistency and content validity. Factor analysis indicated a 2-component solution with good reliability expressed by satisfactory Cronbach α values. IHSS scores were reproducible without changes in the test-retest evaluation (13 treated and 14 untreated patients). Convergent validity analysis showed that IHSS score was correlated with daytime sleepiness, depressive symptoms, and quality of life in patients with IH. The IHSS score was lower in treated than untreated patients (5-8 unit difference, without ceiling effect). The cutoff value for discriminating between untreated and treated patients was 26/50 (sensitivity 55.8%, specificity 78.9%). IHSS scores were higher in drug-free IH patients than NT1 and controls. The best cutoff value to differentiate between untreated IH patients and controls was 22 (sensitivity 91.1%, specificity 94.5%), and 29 with NT1., Conclusions: The IHSS is a reliable and valid clinical tool for the quantification of IH symptoms and consequences that might be useful for patient identification, follow-up, and management., (© 2019 American Academy of Neurology.)

Sleep disorders are frequent and can have serious consequences on patients' health and quality of life. While some sleep disorders are more challenging to treat, most can be easily managed with adequate interventions. We review the main diagnostic features of 6 major sleep disorders (insomnia, circadian rhythm disorders, sleep-disordered breathing, hypersomnia/narcolepsy, parasomnias, and restless legs syndrome/periodic limb movement disorder) to aid medical practitioners in screening and treating sleep disorders as part of clinical practice., (Copyright © 2018. Published by Elsevier Inc.)

Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin (hcrt) neurons in the hypothalamus. Cerebrospinal fluid (CSF) hcrt-1 measurement has been well established as a gold standard of narcolepsy diagnosis, although some portions of narcoleptic patients show normal hcrt-1 levels. We aimed to examine peptide degradation of hcrt-1 and its abnormality in the CSF of patients by using high performance liquid chromatography (HPLC) followed by radioimmunoassay (RIA). CSF was collected from healthy controls, narcoleptic patients of type 1 with hcrt-1 deficiency, type 1 with normal hcrt-1 level, and type 2 with normal hcrt-1 level. We found that the majority of hcrt-1 immunoreactivity in extracted CSF was derived from unauthentic hcrt-1 peaks, which are predicted to be inactive metabolites, and the intact hcrt-1 peptide was less than 10% of the gross amount, suggesting that the regular RIA for CSF hcrt-1 measures largely reflect the unauthentic hcrt-1-related metabolites rather than the intact one. As expected, all hcrt-1-related peaks were abolished in type 1 with hcrt-1 deficiency. Importantly, we also found that the sum of the authentic hcrt-1 peptide (peaks 3 and 4) significantly decreased in non-deficient type 1 and tended to decrease in type 2 narcoleptic patients although the levels with the regular RIA in non-extracted CSF was equivalent to healthy controls. Immunoreactivity with unauthentic hcrt-1 metabolites may masks the possible decline in authentic hcrt-1 level caused by the partial loss of hcrt neurons. Our findings may provide new insights into the degradation of the hcrt-1 peptide and the pathophysiology of narcolepsy.

Narcolepsy is a disease related to hypersomnia type-sleep disorders and characterized by the following manifestations: excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed night sleep. There are several models of the disease pathogenesis each of them assumes the autoimmune nature of the disease. In this regard, it is necessary to develop etiological approaches to the treatment of the disease.

Narcolepsy is a chronic disorder of hypersomnia that can have a significant impact on quality of life and livelihood. However, with appropriate treatment, its symptoms are manageable, and a satisfying personal, social, and professional life can still be enjoyed. Greater awareness of the disorder promotes accurate and efficient diagnosis. With ongoing research into its underlying biology, better treatments for narcolepsy will inevitably become available., (Copyright © 2018 Cleveland Clinic.)