Estimating the prevalence and clinical causality of obstructive sleep apnea in paediatric narcolepsy patients.

BACKGROUND: Numerous risk factors in paediatric narcolepsy may predispose them to obstructive sleep apnea (OSA). The concurrent presence of OSA in these patients might lead to underdiagnosing narcolepsy. This research investigates the prevalence and potential causality between OSA and paediatric narcolepsy. METHODS: A case-control study coupled with a two-sample Mendelian randomization (MR) analysis was employed to explore the prevalence and causal link between paediatric narcolepsy and OSA risk. RESULTS: The case-control study revealed that paediatric narcolepsy patients are at an increased risk of OSA, with an Odds ratio (OR) of 4.87 (95% CI: 2.20-10.71; P < 0.001). The inverse-variance weighted (IVW) model further suggests a potential causal link between narcolepsy and OSA (IVW OR: 4.671, 95% CI: 1.925-11.290; P < 0.001). Additionally, sensitivity analysis confirmed these findings' reliability. CONCLUSION: The findings highlight an elevated prevalence and genetic susceptibility to OSA among paediatric narcolepsy patients, underscoring the necessity for clinical screening of OSA. Continued research is essential to clarify the pathogenic mechanisms and develop potential treatments.

The electroretinography to identify biomarkers of idiopathic hypersomnia and narcolepsy type 1.

Hypersomnia spectrum disorders are underdiagnosed and poorly treated due to their heterogeneity and absence of biomarkers. The electroretinography has been proposed as a proxy of central dysfunction and has proved to be valuable to differentiate certain psychiatric disorders. Hypersomnolence is a shared core feature in central hypersomnia and psychiatric disorders. We therefore aimed to identify biomarkers by studying the electroretinography profile in patients with narcolepsy type 1, idiopathic hypersomnia and in controls. Cone, rod and retinal ganglion cells electrical activity were recorded with flash-electroretinography in non-dilated eye of 31 patients with idiopathic hypersomnia (women 84%, 26.6 ± 5.9 years), 19 patients with narcolepsy type 1 (women 63%, 36.6 ± 12.7 years) and 43 controls (women 58%, 30.6 ± 9.3 years). Reduced cone a-wave amplitude (p = 0.039) and prolonged cone (p = 0.022) and rod b-wave (p = 0.009) latencies were observed in patients with narcolepsy type 1 as compared with controls, while prolonged photopic negative response-wave latency (retinal ganglion cells activity) was observed in patients with idiopathic hypersomnia as compared with controls (p = 0.033). The rod and cone b-wave latency clearly distinguished narcolepsy type 1 from idiopathic hypersomnia and controls (area under the curve > 0.70), and the photopic negative response-wave latency distinguished idiopathic hypersomnia and narcolepsy type 1 from controls with an area under the curve > 0.68. This first original study shows electroretinography anomalies observed in patients with hypersomnia. Narcolepsy type 1 is associated with impaired cone and rod responses, whereas idiopathic hypersomnia is associated with impaired retinal ganglion cells response, suggesting different phototransduction alterations in both hypersomnias. Although these results need to be confirmed with a larger sample size, the electroretinography may be a promising tool for clinicians to differentiate hypersomnia subtypes.

Barriers to therapy adherence in narcolepsy.

BACKGROUND: Treatment adherence (TA) in narcolepsy is a complex phenomenon influenced by various factors beyond patient-related aspects. The management of narcolepsy involves non-pharmacological and symptomatic pharmacological treatment. Factors such as chronic daytime sleepiness, cognitive deficits, psychiatric comorbidities and adverse effects of pharmacological treatment are aspects of narcolepsy that could undermine TA, impacting patients' ability or willingness to consistently follow treatment plans. The aim of this study was to identify the factors influencing TA in narcolepsy and to determine the most significant barriers to adherence. METHODS: An online survey was conducted during the pandemic, assessing demographic and clinical data, medication usage, and adverse effects of treatment. Various questionnaires, such as the Adherence Barriers Questionnaire (ABQ) and Epworth Sleepiness Scale (ESS), were utilized. The ABQ identified patient-specific barriers to medication adherence, while the Patient Health Questionnaire (PHQ-9) assessed depressive symptoms. RESULTS: We analyzed 243 narcolepsy patients (77 % female, mean age 35.7 ± 12.3 years) with 71 % having narcolepsy type 1 (NT1). The average ESS score was 16.4 (SD ± 3.7). Adherence barriers (AB) were identified in 89 % of patients (216/243) based on ABQ score. The most common barriers reported were "Forgetfulness" (77 %), "Depression" (57 %), and "Side effect-driven medication reduction/stopping behavior" (49 %). Approximately 72 % of patients reported side effects from their narcolepsy medication, leading to discontinuation in 78 % of cases. A moderate correlation was found between the severity of adherence barriers (ABQ score) and levels of depression (PHQ-9 score; rs = 0.412, p = 00.000), as well as ESS score (p = . 048). The results of this study may have been influenced by the pandemic situation. CONCLUSION: Adherence barriers are common (89 %) and diverse among people with narcolepsy. Many barriers are related to excessive daytime sleepiness (EDS), cognitive deficits or depressive symptoms, highlighting the importance of recognizing and addressing them for optimal TA. Medication side effects, especially occurring when polypharmacology is utilized, also significantly contribute to adherence challenges. Effective communication regarding therapy adherence and improved detection and management of EDS and depression are crucial for enhancing TA in narcolepsy patients.

A scoping review of the evidence on pharmacological and non-pharmacological interventions for idiopathic hypersomnia.

STUDY OBJECTIVES: Idiopathic hypersomnia (IH) is characterized by excessive sleepiness during the day, prolonged sleep at night, and difficulty waking up. The true prevalence of IH is uncertain. ICSD provides criteria for diagnosing IH; however, the definition has evolved. Managing IH involves using pharmacologic and non-pharmacologic approaches, although the most effective strategies are still unclear. The objective of this scoping review was to identify the extent, range, and nature of the available evidence, identify research gaps, and discuss the implications for clinical practice and policy. METHODS: To conduct this review, a comprehensive search was conducted across scientific databases, without any restrictions on the date or study type. Eligible studies examined the effectiveness of pharmacologic and non-pharmacologic treatments for IH and reported the outcomes of these interventions. Data from the studies were screened, analyzed, and synthesized to provide an overview of the available literature landscape. RESULTS: 51 studies were included in this review, which used various methods and interventions. Pharmacological treatments, particularly modafinil, have been frequently studied and have yielded positive results. There is also emerging evidence for alternative medications such as low-sodium oxybate and pitolisant. Non-pharmacological approaches, such as CBT-H and tDCS have also shown promise in managing IH. CONCLUSIONS: This review highlights the complexity of managing IH management and emphasizes the need for personalized multidisciplinary approaches. Pharmacological interventions are important in managing IH and can be complemented by non-medication strategies. Larger-scale studies are necessary to advance our understanding of IH and to improve treatment outcomes.

Long-term follow-up of symptom and quality of life changes in patients with narcolepsy during and after the COVID-19 pandemic.

The COVID-19 pandemic may have a significant impact on patients with narcolepsy, yet a long-term follow-up study is currently lacking. This study aims to investigate changes in symptom severity and the quality of life of patients with narcolepsy during and after the pandemic. Patients with type 1 or type 2 narcolepsy (NT1, NT2) were retrospectively recruited and prospectively followed from 2020 to 2023. They received evaluations including the Epworth Sleepiness Scale (ESS), the visual analog scale (VAS) for hypersomnolence, the VAS for cataplexy, the Short-form 36 Health Survey questionnaire (SF-36), and a sleep diary. We compared the differences between the pre-lockdown, the lockdown, the post-lockdown, and the post-pandemic periods by repeated measures ANOVA or the Friedman test, with the Bonferroni test for post hoc analysis. A total of 100 patients completed the 4-year study (mean age, 24.06 ± 7.00 years; 55% male). We observed significant differences in the ESS (p = 0.037), total nighttime sleep (p = 0.03), total sleep time (p = 0.035), and sleep efficiency (p = 0.035) during the study period. There was also significantly worse physical role functioning in the post-pandemic period (p = 0.014). In particular, the NT1 group had significantly decreased VAS-C scores (p < 0.001) but experienced worse physical role functioning in the post-pandemic period (p = 0.009). Patients with narcolepsy continue to face challenges after the pandemic. A more flexible lifestyle with an adequate sleep time may be beneficial, and medication adherence should be emphasized.

A Dialogue about Vaccine Side Effects: Understanding Difficult Pandemic Experiences.

This paper investigates the relationship between the experiences of mass vaccinations against two pandemic viruses: the swine flu in 2009-2010 and COVID-19 in the early 2020s. We show how distressing memories from the swine flu vaccination, which led to the rare but severe adverse effect of narcolepsy in approximately 500 children in Sweden, were triggered by the COVID-19 pandemic. The narcolepsy illness story has rarely been told in academic contexts; therefore, we will provide space for this story. It is presented through a dialogue with the aim of shedding light on the interrelationship between pandemics-and between mass vaccinations-to investigate what could be termed cultural wounds that influence societies because they are characterized by the difficulty of talking about them. The paper explores the multiple shocks of illness in life and what can be learned from them by sharing them.

Novel biomarkers derived from the Maintenance of Wakefulness Test as predictors of sleepiness and response to treatment.

The Maintenance of Wakefulness Test (MWT) is a widely accepted objective test used to evaluate daytime somnolence and is commonly used in clinical studies evaluating novel therapeutics for excessive daytime sleepiness. In the latter, sleep onset latency (SOL) is typically the sole MWT endpoint. Here, we explored microsleeps, sleep probability measures derived from automated sleep scoring, and quantitative electroencephalography (qEEG) features as additional MWT biomarkers of daytime sleepiness, using data from a phase 1B trial of the selective orexin receptor 2 agonist danavorexton (TAK-925) in people with narcolepsy type 1 (NT1) or type 2 (NT2). Danavorexton treatment reduced the rate and duration of microsleeps during the MWT in NT1 (days 1 and 7; p ≤ 0.005) and microsleep rate in NT2 (days 1 and 7; p < 0.0001). Use of an EEG-sleep-staging-derived measure to determine the probability of wakefulness for each minute revealed a novel metric to track changes in daytime sleepiness, which were consistent with the θ/α ratio, a known biomarker of drowsiness. The slopes of line-fits to both the log-transformed sleepiness score or log-transformed θ/α ratio correlated well to (inverse) MWT SOL for NT1 (R = 0.93 and R = 0.83, respectively) and NT2 (R = 0.97 and R = 0.84, respectively), suggesting that individuals with narcolepsy have increased sleepiness immediately after lights-off. These analyses demonstrate that novel EEG-based biomarkers can augment SOL as predictors of sleepiness and its response to treatment and provide a novel framework for the analysis of wake EEG in hypersomnia disorders.

High-resolution HLA sequencing and hypocretin receptor 2 autoantibodies in narcolepsy type 1 and type 2.

Narcolepsy is a sleep disorder caused by an apparent degeneration of orexin/hypocretin neurons in the lateral hypothalamic area and a subsequent decrease in orexin/hypocretin levels in the cerebrospinal fluid. Narcolepsy is classified into type 1 (NT1) and type 2 (NT2). While genetic associations in the human leukocyte antigen (HLA) region and candidate autoantibodies have been investigated in NT1 to imply an autoimmune origin, less is known about the pathogenesis in NT2. Twenty-six NT1 and 15 NT2 patients were included, together with control groups of 24 idiopathic hypersomnia (IH) patients and 778 general population participants. High-resolution sequencing was used to determine the alleles, the extended haplotypes, and the genotypes of HLA-DRB3, -DRB4, -DRB5, -DRB1, -DQA1, -DQB1, -DPA1, and -DPB1. Radiobinding assay was used to determine autoantibodies against hypocretin receptor 2 (anti-HCRTR2 autoantibodies). NT1 was associated with HLA-DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01, -DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01 (odds ratio [OR]: 9.15; p = 8.31 × 10-4) and HLA-DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01, -DRB4*01:03:01, -DRB1*04:01:01, -DQA1*03:02//03:03:01, -DQB1*03:01:01 (OR: 23.61; p = 1.58 × 10-4) genotypes. Lower orexin/hypocretin levels were reported in the NT2 subgroup (n = 5) that was associated with the extended HLA-DQB1*06:02:01 haplotype (p = .001). Anti-HCRTR2 autoantibody levels were not different between study groups (p = .8524). We confirmed the previous association of NT1 with HLA-DQB1*06:02:01 extended genotypes. A subgroup of NT2 patients with intermediate orexin/hypocretin levels and association with HLA-DQB1*06:02:01 was identified, indicating a possible overlap between the two distinct narcolepsy subtypes, NT1 and NT2. Low anti-HCRTR2 autoantibody levels suggest that these receptors might not function as autoimmune targets in either NT1 or NT2.

Machine learning-Based model for prediction of Narcolepsy Type 1 in Patients with Obstructive Sleep Apnea with Excessive Daytime Sleepiness.

Background: Excessive daytime sleepiness (EDS) forms a prevalent symptom of obstructive sleep apnea (OSA) and narcolepsy type 1 (NT1), while the latter might always be overlooked. Machine learning (ML) models can enable the early detection of these conditions, which has never been applied for diagnosis of NT1. Objective: The study aimed to develop ML prediction models to help non-sleep specialist clinicians identify high probability of comorbid NT1 in patients with OSA early. Methods: Totally, clinical features of 246 patients with OSA in three sleep centers were collected and analyzed for the development of nine ML models. LASSO regression was used for feature selection. Various metrics such as the area under the receiver operating curve (AUC), calibration curve, and decision curve analysis (DCA) were employed to evaluate and compare the performance of these ML models. Model interpretability was demonstrated by Shapley Additive explanations (SHAP). Results: Based on the analysis of AUC, DCA, and calibration curves, the Gradient Boosting Machine (GBM) model demonstrated superior performance compared to other machine learning (ML) models. The top five features used in the GBM model, ranked by feature importance, were age of onset, total limb movements index, sleep latency, non-REM (Rapid Eye Movement) sleep stage 2 and severity of OSA. Conclusion: The study yielded a simple and feasible screening ML-based model for the early identification of NT1 in patients with OSA, which warrants further verification in more extensive clinical practices.

An Unusual Cause of Increasing Excessive Daytime Sleepiness in a CPAP-treated Obstructive Sleep Apnea Patient.

The onset of narcolepsy type 1 (NT1) occurs after 50 years of age in less than 2% of the cases. In older adults, the diagnosis is often delayed due to the presence of neurological degenerative and inflammatory comorbidities and overlapping sleep disorders. We report the case of a 63-year-old man with a 5-year history of excessive daytime sleepiness (EDS) and a 2-year diagnosis of obstructive sleep apnea syndrome (OSAS), which. OSAS was confirmed by respiratory polygraphy that showed an apnea-hypopnea index (AHI) of 71 events/hour of sleep associated with significant nocturnal hypoxemia (lowest oxygen saturation: 53%), which lead to the initiation of continuous positive airway pressure (CPAP) treatment. Cognitive complaints, unexplained spells of dizziness, and lack of improvement in EDS with CPAP led to further diagnostic investigation of infectious, inflammatory, and neurodegenerative disorders. Low hypocretin levels in the cerebrospinal fluid (CSF) confirmed the diagnosis of NT1, and the patient's symptoms improved with the treatment with pitolisant. Though exceptional in older adults, NT1 should be suspected in the presence of atypical EDS with neurological complaints, unexplained dizzy spells, or OSAS that resists the CPAP treatment. Low levels of hypocretin in the CSF are highly specific and rule out other neurological and sleep disorders.

The Changed Nocturnal Sleep Structure and Higher Anxiety, Depression, and Fatigue in Patients with Narcolepsy Type 1.

Purpose: This study aimed to evaluate nocturnal sleep structure and anxiety, depression, and fatigue in patients with narcolepsy type 1 (NT1). Methods: Thirty NT1 patients and thirty-five healthy controls were enrolled and evaluated using the Epworth sleepiness scale (ESS), Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Fatigue Severity Scale (FSS), polysomnography, multiple sleep latency test, and brain function state monitoring. Statistical analyses were performed using SPSS Statistics for Windows, version 23.0. Benjamini-Hochberg correction was performed to control the false discovery rate. Results: Apart from typical clinical manifestations, patients with NT1 are prone to comorbidities such as nocturnal sleep disorders, anxiety, depression, and fatigue. Compared with the control group, patients with NT1 exhibited abnormal sleep structure, including increased total sleep time (P adj=0.007), decreased sleep efficiency (P adj=0.002), shortening of sleep onset latency (P adj<0.001), elevated wake after sleep onset (P adj=0.002), increased N1% (P adj=0.006), and reduced N2%, N3%, and REM% (P adj=0.007, P adj<0.001, P adj=0.013). Thirty-seven percent of patients had moderate to severe obstructive sleep apnea-hypopnea syndrome. And sixty percent of patients were complicated with REM sleep without atonia. Patients with NT1 displayed increased anxiety propensity (P adj<0.001), and increased brain fatigue (P adj=0.020) in brain function state monitoring. FSS scores were positively correlated with brain fatigue (P adj<0.001) and mean sleep latency was inversely correlated with FSS scores and brain fatigue (P adj=0.013, P adj=0.029). Additionally, ESS scores and brain fatigue decreased after 3 months of therapy (P=0.012, P=0.030). Conclusion: NT1 patients had abnormal nocturnal sleep structures, who showed increased anxiety, depression, and fatigue. Excessive daytime sleepiness and fatigue improved after 3 months of treatment with methylphenidate hydrochloride prolonged-release tablets in combination with venlafaxine.

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 weeks, 8 weeks, 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 pre-specified 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 group met the MCID for additional measures including social and cognitive functioning, daytime sleepiness, hypersomnia symptoms, and hypersomnia-related functioning. CONCLUSION: 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.

Evaluating routine blood and cerebrospinal fluid samples in narcolepsy patients.

Cerebrospinal fluid hypocretin-1 is proven to be a precise diagnostic marker of narcolepsy Type 1 (NT1). However other characteristics of cerebrospinal fluid and blood parameters have not yet been described. The objective of this study was to evaluate the differences in routine blood and cerebrospinal fluid analyses between NT1 patients and patients suspected of hypersomnia. We collected retrospectively all measures of cerebrospinal fluid hypocretin-1 between 2019 and 2022. This yielded 612 patients out of which 146 were diagnosed with NT1 and the rest (466 patients) were used as a control group. We selected the most relevant routine samples from both blood, plasma and cerebrospinal fluid and compared the two groups. The only significantly different analytes were plasma lactate dehydrogenase and cerebrospinal fluid hypocretin-1. No other differences were found between the groups including thyroid markers, markers of neuroendocrine function, inflammatory markers in blood or cerebrospinal fluid, markers of permeability of the blood brain barrier or metabolic markers in blood samples. We found no significant differences in routine blood or cerebrospinal fluid components, neuroendocrine function, neuroinflammation and metabolic markers. The results reflect that the hypocretin system does not seem to play a chronic major role in regulation of these markers. None of the parameters routinely measured in blood in these patients could differentiate between NT1 and non-NT1 disorders besides CSF-hcrt-1.

Impaired Cognition in Narcolepsy: clinical and neurobiological perspectives.

In addition to well-known symptoms such as sleepiness and cataplexy, many people with narcolepsy have impaired cognition, reporting inattention, poor memory and other concerns. Unfortunately, research on cognition in narcolepsy has been limited. Strong evidence demonstrates difficulties with sustained attention, but evidence for executive dysfunction and impaired memory is mixed. Animal research provides some insights into how loss of the orexin neurons in narcolepsy type 1 may give rise to impaired cognition via dysfunction of the prefrontal cortex, and cholinergic and monoaminergic systems. This paper reviews some of these clinical and preclinical findings, provides a neurobiological framework to understand these deficits, and highlights some of the many key unanswered questions.

Sleep regulation and host genetics.

Due to the multifactorial and complex nature of rest, we focus on phenotypes related to sleep. Sleep regulation is a multifactorial process. In this chapter, we focus on those phenotypes inherent to sleep that are highly prevalent in the population, and that can be modulated by lifestyle, such as sleep quality and duration, insomnia, restless leg syndrome and daytime sleepiness. We, therefore, leave in the background those phenotypes that constitute infrequent pathologies or for which the current level of scientific evidence does not favour the implementation of practical approaches of this type. Similarly, the regulation of sleep quality is intimately linked to the regulation of the circadian rhythm. Although this relationship is discussed in the sections that require it, the in-depth study of circadian rhythm regulation at the molecular level deserves a separate chapter, and this is how it is dealt with in this volume.

Narcolepsy and risk of traumatic injury: a population-based matched cohort study.

STUDY OBJECTIVES: We evaluated the risk of traumatic injury in patients with narcolepsy compared to the general population. METHODS: We conducted a population-based matched cohort study using a Japanese health insurance claims database. For each patient with narcolepsy, up to 5 individuals from the general population without narcolepsy were matched by variables such as sex, age, and cohort entry month. The primary outcome was traumatic injury, and the secondary outcome was fracture. The study population was followed for up to 5 years from the cohort entry date. We estimated crude incidence rates, adjusted incidence rate differences (aIRDs), adjusted hazard ratios (aHRs), and their 95% confidence intervals (CIs) for study outcomes using crude and multivariable Poisson and Cox regression models. RESULTS: We included 2,451 patients with narcolepsy (mean age, 30.3 years; male, 58.0%) and 10,591 matched individuals (mean age, 30.6 years; male, 58.4%). Crude incidence rate of traumatic injury was 11.4 per 100 person-years for patients with narcolepsy compared with 6.2 per 100 person-years for matched individuals (aIRD, 6.2 excess events per 100 person-years [95% CI, 4.9-7.4]; aHR, 1.8 [95% CI, 1.5-2.2]). Crude incidence rate of fracture was 2.3 per 100 person-years for patients with narcolepsy compared with 1.3 per 100 person-years for matched individuals (aIRD, 1.2 excess events per 100 person-years [95% CI, 0.7-1.7]; aHR, 1.7 [95% CI, 1.4-2.1]). CONCLUSIONS: Narcolepsy was associated with increased risk of traumatic injury. For patients with narcolepsy, optimized approaches to injury prevention should be considered.

Causal relationship between narcolepsy and anxiety: A two-sample Mendelian randomization study.

BACKGROUND: The aim of this study was to assess the causal relationship between narcolepsy and anxiety using Mendelian randomization (MR) methodology. METHODS: Our research applied a bidirectional two-sample Mendelian Randomization strategy to explore the linkage between narcolepsy and anxiety. Utilizing summary data from GWAS on both conditions, we primarily employed the inverse-variance weighted technique for our analysis. To evaluate heterogeneity and horizontal pleiotropy, we utilized tools such as the MR Egger method, the weighted median method, Cochran's Q statistic, and the MR Egger intercept. RESULTS: The analysis using the inverse variance-weighted method showed a clear positive link between narcolepsy and anxiety, with an odds ratio of 1.381 (95% CI: 1.161-1.642, p < 0.001). Tests for heterogeneity and horizontal pleiotropy, including MR Egger and IVW methods, indicated no significant findings (p-values 0.616 and 0.637, respectively, for heterogeneity; p = 0.463 for pleiotropy). Furthermore, no reverse causation was observed between anxiety and narcolepsy (odds ratio 1.034, 95% CI: 0.992-1.078, p = 0.111), with consistent findings across various analytical approaches. CONCLUSION: This research suggests a possible causal link between narcolepsy and anxiety disorders. The results illuminate this connection and advocate additional studies to elucidate the mechanisms involved and to identify effective interventions.

Executive function performance in children and adolescent patients with narcolepsy type 1.

OBJECTIVE: The executive function profile in patients with narcolepsy type 1 (NT1) has been mentioned; however, limited research exists on children and adolescent patients with NT1.This study aims to assess executive function in children and adolescent patients with NT1 in China, examine potential influencing factors and evaluate the short-term treatment effect on executive function. METHODS: 53 NT1 patients (36 males, age 12.2 ± 3.4 years) and 37 healthy controls (23 males, age 12.2 ± 2.5 years) underwent self-reported measures assessing subjective sleepiness, depression, anxiety and sleep quality. A comprehensive neuropsychological test was administered to assess executive function domains, including processing speed, inhibitory control, cognitive flexibility and working memory. These assessments were repeated in NT1 patients after three-day regular drug treatment. RESULTS: NT1 patients exhibited higher levels of excessive daytime sleepiness, depression, anxiety, and poor sleep quality compared to healthy controls. Patients showed impaired processing speed, inhibitory control and cognitive flexibility (p < 0.05), whereas working memory was unaffected (p > 0.05). Regression analysis revealed that parameters from sleep monitoring, such as sleep efficiency and sleep latency, were correlated with executive function performance after controlling for age, gender, and education years. The short-term treatment led to improvements in inhibitory control, cognitive flexibility, and working memory. CONCLUSION: The findings showed that executive function was impaired among children and adolescent patients with NT1, which was associated with objective sleep parameters. Furthermore, this study emphasizes the necessity of neuropsychological assessments and early interventions among children and adolescent NT1 patients.

Development and validation of a machine learning model for prediction of comorbid major depression disorder among narcolepsy type 1.

BACKGROUND: Major depression disorder (MDD) forms a common psychiatric comorbidity among patients with narcolepsy type 1 (NT1), yet its impact on patients with NT1 is often overlooked by neurologists. Currently, there is a lack of effective methods for accurately predicting MDD in patients with NT1. OBJECTIVE: This study utilized machine learning (ML) algorithms to identify critical variables and developed the prediction model for predicting MDD in patients with NT1. METHODS: The study included 267 NT1 patients from four sleep centers. The diagnosis of comorbid MDD was based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5). ML models, including six full models and six compact models, were developed using a training set. The performance of these models was compared in the testing set, and the optimal model was evaluated in the testing set. Various evaluation metrics, such as Area under the receiver operating curve (AUC), precision-recall (PR) curve and calibration curve were employed to assess and compare the performance of the ML models. Model interpretability was demonstrated using SHAP. RESULT: In the testing set, the logistic regression (LG) model demonstrated superior performance compared to other ML models based on evaluation metrics such as AUC, PR curve, and calibration curve. The top eight features used in the LG model, ranked by feature importance, included social impact scale (SIS) score, narcolepsy severity scale (NSS) score, total sleep time, body mass index (BMI), education years, age of onset, sleep efficiency, sleep latency. CONCLUSION: The study yielded a straightforward and practical ML model for the early identification of MDD in patients with NT1. A web-based tool for clinical applications was developed, which deserves further verification in diverse clinical settings.

Comparing the Prevalence of Sleep Disorders Among Underweight, Normal, Overweight, and Obese Adults in Riyadh, Saudi Arabia.

Background Sleep disorders are prevalent worldwide and can have a negative impact on physical and psychological well-being. Numerous studies have explored the reciprocal connection between obesity and sleep disorders. This study aimed to compare the prevalence of sleep disorders among underweight, normal, overweight, and obese adults in Riyadh, Saudi Arabia. Methods This cross-sectional study was conducted on 378 adults visiting primary healthcare centers in Riyadh, Saudi Arabia, from August to November 2022. Data were collected using a self-administered questionnaire that included a section for demographic data and the SLEEP-50 questionnaire in both English and Arabic languages. Results Most of the participants were aged between 25 and 34 years (37.6%), 79.1% were females and 59.5% were either overweight or obese. Most participants (78.3%) had at least one sleep disorder, with narcolepsy being the most frequent disorder (65.1%), and 23% had two combined sleep disorders. Obese and overweight patients were significantly more likely to have sleep disorders (p=0.011), and obese patients were more likely to have all sleep disorders (p=0.049). Conclusion The prevalence of sleep disorders, namely narcolepsy and insomnia, is high among adults in Riyadh, Saudi Arabia. Moreover, sleep disorders are significantly associated with obesity. Evaluation and management of sleep disorders in clinical settings among patient with overweight or obese is important to improve their quality of life and to prevent physical and psychological complications.