Hypnosis: An aid in working with patients with narcolepsy.

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.

Development of a mindfulness-based intervention for narcolepsy: a feasibility study.

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.

Incidence of pediatric narcolepsy diagnosis and management: evidence from claims data.

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.

Vagus nerve stimulation for the treatment of narcolepsy.

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.

Idiopathic Hypersomnia and Kleine-Levin Syndrome: Primary Disorders of Hypersomnolence Beyond Narcolepsy.

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.

Clinical Evaluation and Management of Narcolepsy in Children and Adolescents.

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.

Sleep Disorders in Childhood.

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.

Narcolepsies, update in 2023.

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.

Circadian rhythm of daytime sleepiness in pediatric narcolepsy: A pilot study.

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.

Narcolepsy and Idiopathic Hypersomnia.

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.

School Problems and School Support for Children with Narcolepsy: Parent, Teacher, and Child Reports.

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.

Pediatric sleep: current knowledge, gaps, and opportunities for the future.

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.

Approach to a sleepy child: Diagnosis and treatment of excessive daytime sleepiness in children and adolescents.

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.

Evaluation of psychometric properties of patient-reported outcome measures frequently used in narcolepsy randomized controlled trials: a systematic review.

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.

Narcolepsy.

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.

Common Sleep Disorders in Adults: Diagnosis and Management.

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.

Child Neurology: A Case Series of Heterogeneous Neuropsychiatric Symptoms and Outcome in Very Early-Onset Narcolepsy Type 1.

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.

Development and Validation of the Pediatric Hypersomnolence Survey.

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.

Activity of putative orexin neurons during cataplexy.

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.