Background Narcolepsy is a chronic sleep disorder that is characterized by excessive daytime sleepiness and cataplexy. It has been increasingly diagnosed over the years, impacting productivity and employment rates. Awareness of healthcare providers is crucial for the early identification and management of this condition. Objectives This study assessed physicians\' knowledge of narcolepsy in the Makkah region of Saudi Arabia. Method This cross-sectional study was conducted from February to November 2023. An online self-administered questionnaire has been used to target physicians working in the Makkah region of Saudi Arabia. The utilized questionnaire assessed demographic and professional data as well as the participants\' knowledge of narcolepsy. Statistical analysis was performed using RStudio (R version 4.3.1.). Statistical differences in knowledge were assessed using Pearson\'s chi-squared and Fisher\'s exact tests. Factors associated with knowledge of narcolepsy were investigated through univariable and multivariable regression analyses expressed using beta coefficients and 95% confidence intervals (95% CIs). Statistical significance was considered at p < 0.05. Results A total of 226 physicians participated in this study. Male physicians (54.4%, n = 123), practicing in governmental hospitals (77.9%, n = 176) and residing in Makkah City (43.4%, n = 98) were predominant. Non-surgical specialties represented 73.5% (n = 166) of the sample. Around 81% (n = 184) of the participants were aware of narcolepsy, with a significant difference according to professional status (p = 0.045). The majority of physicians have correctly identified narcolepsy as a sleep disorder (78.3%, n = 177), but only 32.3% (n = 73) have identified its typical onset age group and recognized that there are two types of narcolepsy. Almost half of the respondents indicated a lack of knowledge about the diagnostic criteria for narcolepsy in the DSM-5 (52.2%, n = 118). Only 27.4% (n = 62) recognized the correct diagnostic criteria. Half of the sample (51.3%, n = 116) recognized the use of multiple sleep latency tests for the diagnosis. For factors associated with higher participants\' knowledge, non-surgical specialties showed significantly higher knowledge scores compared to surgical specialties (beta = 0.91, 95% CI, 0.13 to 1.7, p = 0.024). Conclusion This study has revealed a significant lack of knowledge about narcolepsy among physicians in Makkah region. This raises concerns about the timely identification, proper understanding, and accurate diagnosis of patients with narcolepsy. Adequate understanding of narcolepsy is crucial to avoid its misdiagnosis or delays in receiving appropriate treatment and support, ultimately impacting their quality of life.

BACKGROUND: The study seeks to assess serum neurofilament light chain (NfL) levels in paediatric narcolepsy-diagnosed patients. Moreover, it aims to explore the correlation between NfL levels and the severity of narcolepsy symptoms, sleep quality, and manifestations of anxiety and depression.
METHODS: This retrospective analysis included 98 paediatric narcolepsy cases and 100 controls matched for age and gender. The study focused on comparing serum NfL levels across these groups. Severity of EDS in patients was measured with the Epworth Sleepiness Scale (ESS). Moreover, the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale-24 (HAMD-24), and Hamilton Anxiety Scale-14 (HAMA-14) were used to assess narcolepsy symptoms, sleep quality, and psychological conditions.
RESULTS: Patients with paediatric narcolepsy had significantly higher serum NfL levels than controls (P < 0.05). Additionally, a positive correlation was found between serum NfL levels and ESS scores (P < 0.001). An independent link between serum NfL and paediatric narcolepsy was established via multiple logistic regression (OR = 0.943, 95 % CI = 0.921-0.993, P = 0.004). Moreover, serum NfL\'s diagnostic precision for paediatric narcolepsy was evident from the ROC curve area of 0.938 (95 % CI: 0.86-0.99, P < 0.001).
CONCLUSIONS: The study implies a positive correlation between increased serum NfL levels and the severity of paediatric narcolepsy. Nevertheless, the causative link between serum NfL levels and paediatric narcolepsy remains uncertain, highlighting the need for larger sample sizes and well-structured cohort studies to offer more definitive.

UNASSIGNED: Excessive daytime sleepiness (EDS) can have a significant impact on health and quality of life but may remain undiagnosed due to low awareness and underestimation of the clinical impact of the symptoms. An online screening tool supported by media campaigns might increase awareness and help detect undiagnosed cases of EDS and narcolepsy. The aim of this study was to develop an online screening method, along with a media campaign focusing on EDS, and evaluate its feasibility.
UNASSIGNED: Online screening supported by a media campaign targeting young and middle-aged adults (18-45 years old) were developed and implemented over a period of 1 year starting from November 2022. The Epworth Sleepiness Scale was used to identify EDS, and the Swiss Narcolepsy Scale was used to identify narcolepsy. In addition, the data on sociodemographic characteristics, selected sleep and health indicators and lifestyle behaviors were collected to indicate the etiology of the EDS. Feasibility, e.g., implementation and practicality, was assessed by the response rate, response to the promotion strategy, time spent on the tool, sample characteristics, and the prevalence of identified EDS and narcolepsy cases.
UNASSIGNED: A total of 2,390 people opened the screening link; 568 of them completed the online screening (23.8%), and most of them (n = 437, 76.9%) left their contact data to receive feedback. We identified 171 (30.1%) respondents at risk of EDS and 61 (10.7%) at risk of narcolepsy. The mean time of the screening was 15 min.
UNASSIGNED: An online screening tool supported with a campaign seems to be a feasible way to increase awareness about EDS and prevent delayed detection of EDS cases.

OBJECTIVE: Individuals with narcolepsy are more likely to be obese than the general population. Changes in weight-related measures with extended-release, once-nightly sodium oxybate (ON-SXB) and characteristics of participants with ≥5% weight loss were assessed in a Randomized study Evaluating the efficacy and SafeTy of a ONce nightly formulation of sodium oxybate (REST-ON) trial post hoc analysis.
METHODS: REST-ON (NCT02720744) was a Phase III, double-blind, placebo-controlled, multicenter, randomized clinical trial. Participants aged ≥16 years with narcolepsy type 1 (NT1) or NT2 received ON-SXB or placebo for 13 weeks (week 1, 4.5 g; weeks 2-3, 6 g; weeks 4-8, 7.5 g; and weeks 9-13, 9 g). Weight and body mass index were measured at baseline and study end.
RESULTS: Weights were similar between groups at baseline (mean [SD]; ON-SXB, 81.2 [20.8] kg; N = 107 [NT1, n = 80; NT2, n = 27]; placebo, 82.1 [22.5] kg; N = 105 [NT1, n = 82; NT2, n = 23]). At week 13 (9 g), mean (SD) weight decreased 1.3 (3.6) kg with ON-SXB and increased 0.2 (2.6) kg with placebo; 17.8% (19/107; NT1, n = 14; NT2, n = 5) of participants receiving ON-SXB had ≥5% weight loss versus 3.8% receiving placebo (4/105; NT1, n = 3; NT2, n = 1; P = 0.001). At week 13, least squares mean (SE) body mass index change from baseline was ‒0.51 (0.13) kg/m2 with ON-SXB and 0.08 (0.13) kg/m2 with placebo (least squares mean difference [95% CI], -0.59 [-0.95 to -0.23] kg/m2; P = 0.001). Excessive daytime sleepiness improved for both groups with ON-SXB, the ≥5% weight-loss subgroup exhibited larger improvement in the Maintenance of Wakefulness Test and Epworth Sleepiness Scale versus the other subgroup (weight loss <5%, no change, or weight gain) (Maintenance of Wakefulness Test, P = 0.019; Epworth Sleepiness Scale score, P < 0.001).
CONCLUSIONS: Narcolepsy is often associated with obesity, which may increase cardiometabolic risks. ON-SXB, an effective treatment for excessive daytime sleepiness and cataplexy, may be preferred in overweight or obese individuals to provide a more tailored treatment approach.
RESULTS:
UNASSIGNED: NCT02720744.

OBJECTIVE: Idiopathic hypersomnia (IH) is a disorder of central hypersomnolence that results in excessive daytime sleepiness in the absence of another identifying cause. Case studies from sleep clinic patients may not be a fair representation of the wider IH population. This study aims to better characterize patients diagnosed with IH in Australia and New Zealand using online patient-driven survey data.
METHODS: A retrospective analysis of 686 participants from the Hypersomnolence Australia Patient Data Registry diagnosed with either IH (n = 554), narcolepsy type 1 (NT1, n = 54) or narcolepsy type 2 (NT2, n = 78) between January 2013 and October 2022 was performed.
RESULTS: Participants with IH reported additional sleep disorders such as OSA (16.4%) and restless legs syndrome (7.9%) and notable comorbidities included depression (46.2%) and anxiety (50%). There was a mean delay in diagnosis of 10 years in participants with IH, when compared to symptom onset. IH presents with unique but also overlapping symptomatology with NT2, with similar reporting of long daytime naps, unrefreshed sleep and automatic behavior. Modafinil was the most common medication (45.5%) used by participants with IH followed by dexamphetamine (44.2%). Most participants with IH reported receiving physician advice regarding positive lifestyle changes but recommend that newly diagnosed patients be given more advice about medication use.
CONCLUSIONS: This study demonstrates a delay in IH diagnosis when compared to symptom onset and overlapping features of IH and NT2. It also highlights the heterogeneous presentation of IH and the value of large patient registries in future research.

OBJECTIVE: Narcolepsy is a neurologic disorder characterized by irresistible sleep attacks. Although its etiology is unknown, it is strongly associated with genetic variances in the human leukocyte antigen (HLA) complex. We investigated the association of HLA class II-DR-DQ alleles in a sample of patients with narcolepsy-cataplexy (narcolepsy type 1; NT1) and patients with narcolepsy without cataplexy (narcolepsy type 2; NT2) with a control group. Additionally, we compared demographic, clinical, and laboratory characteristics of patients with narcolepsy with or without the DQB1*06:02 allele.
METHODS: This case control study included 21 patients with NT1 (56.8%), 16 patients with NT2 (43.2%), and 100 controls. Sequence-based typing identified HLA-DRB1 alleles, and HLA-DQB1 typing was done using PCR-Sequence-Specific Oligonucleotide. Allele and haplotype frequencies were calculated by direct counting. Nocturnal polysomnography and Multiple Sleep Latency Test were performed in all participants.
RESULTS: In the NT1 group, only one allele had a significantly higher frequency than in the NT2 group: DQB1*06:02 (61.9% vs. 18.8%;). Compared to controls, DQB1*06:02 (61.9% vs. 18.0% in controls) and DRB1*15:01(47.6% vs. 8.0%), had higher frequencies in patients with NT1. Multiple analyses showed that patients with NT1 had an increased chance of being HLA-DQB1*06:02 positive. HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is associated with NT1 in our Brazilian patients. PSG was identified in DQB1*06:02 positive subgroup REM sleep latency (REML) ≤ 15 minutes, and all patients had two or more sleep-onset REM periods (SOREMPs) at MSLT.
CONCLUSIONS: This study showed a strong association between HLA DQB1*06:02 and the haplotype HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 in patients with NT1. Patients with DQB1*0602 allele showed shorter REMLs at PSG. These results reinforce the suggestion of DQB1 genotyping as relevant to narcolepsy screening.

UNASSIGNED: Sleeping disorders were reported in many patients who took vaccines during previous pandemics. We aim to investigate the relationship between coronavirus disease 2019 (COVID-19) vaccines and the incidence of narcolepsy symptoms in the Jordanian population.
UNASSIGNED: We used a descriptive, cross-sectional, online self-administered survey conducted between December 2022 and May 2023. The survey targeted males and females above the age of 18 years who took any type of COVID-19 vaccine, had no chronic diseases, and had no sleep disorders prior to taking the vaccine. The survey was distributed via social media platforms.
UNASSIGNED: A total of 873 participants were included in this study, consisting of 44.4% males and 55.6% females, with the majority being in the 18-29 age group. Most participants (79.8%) received two vaccine doses, with the Pfizer vaccine being the most common. Nearly half of the participants reported excessive daytime sleepiness. Sleep paralysis and hypnagogic hallucinations were reported by a notable proportion of participants, but no significant differences were found among the vaccine types. Sleep attacks and fragmented nighttime sleep were associated with the number of vaccine doses received, suggesting a possible influence of the dose count on these symptoms. The presence of excessive daytime sleepiness, sudden loss of muscle tone, sleep paralysis, and hypnagogic hallucinations showed no significant association with the number of doses taken.
UNASSIGNED: We hypothesize a possible link between COVID-19 vaccination and the emergence of narcolepsy symptoms in Jordanian individuals. Additional investigations and continuous monitoring to determine the extent of the risk and uncover potential mechanisms behind this connection should be performed.

BACKGROUND: Recent studies suggest the existence of a physiologic basis for bone rarefaction and increased risk for fractures. This study aimed to address anthropometric differences between patients with narcolepsy type 1 (NT1) and type 2 (NT2) and discrepancies in bone mineral content (BMC) as a function of hypocretin-1 (Hcrt-1) measured in cerebrospinal fluid (CSF).
METHODS: We have evaluated 31 adult patients (aged 18-65 years) with NT1 and 18 patients with NT2, comparing the groups in terms of anthropometric variables - body mass index (BMI) and waist-to-hip ratio (WHR) - and percentage of bone mineral content (%BMC), measured by bioelectrical impedance analysis (BIA). Statistical analysis assessed the effects of Hcrt-1 levels on CSF, dietary intake, and medication use over these variables. Statistical significance was achieved with a confidence interval of 95 % and p < 0.05.
RESULTS: Patients with NT1 presented with higher BMI (32.04 ± 6.95 vs. 25.38 ± 4.26 kg/m2; p < 0.01) and WHR (0.89 ± 0.09 vs. 0.83 ± 0.09; p = 0.02) compared to NT2, in detriment of %BMC, which was lower for NT1 (4.1 ± 1.02 vs. 4.89 ± 0.59; p < 0.01). Hcrt-1 in CSF showed a positive correlation with %BMC (r = +0.48, p < 0.01) and a negative correlation with anthropometric features (BMI: r = -0.54, p < 0.01; WHR: r = -0.37, p = 0.01). There was a correlation between WHR and diary caloric intake (r = +0.42, p < 0.01).
CONCLUSIONS: The evaluation of patients with narcolepsy presupposes a syndromic approach comprising symptoms that go far beyond excessive daytime sleepiness. The integrated follow-up, including nutritional profile and anthropometric features, should add value in reducing morbidity in this population.

β-amyloid42 (Aβ42) in Alzheimer\'s disease (AD) and orexin in narcolepsy are considered crucial biomarkers for diagnosis and therapeutic targets. Recently, orexin and Aβ cerebral dynamics have been studied in both pathologies, but how they interact with each other remains further to be known. In this study, we investigated the reliability of using the correlation between orexin-A and Aβ42 CSF levels as a candidate marker to explain the chain of events leading to narcolepsy or AD pathology. In order to test the correlation between these biomarkers, patients diagnosed with AD (n = 76), narcolepsy type 1 (NT1, n = 17), narcolepsy type 2 (NT2, n = 23) and healthy subjects (n = 91) were examined. Patients and healthy subjects underwent lumbar puncture between 8:00 and 10:00 am at the Neurology Unit of the University Hospital of Rome \"Tor Vergata\". CSF levels of Aβ42, total-tau, phosphorylated-tau, and orexin-A were assessed. The results showed that CSF levels of Aβ42 were significantly lower (p < 0.001) in AD (332.28 ± 237.36 pg/mL) compared to NT1 (569.88 ± 187.00 pg/mL), NT2 (691.00 ± 292.63 pg/mL) and healthy subjects (943.68 ± 198.12 pg/mL). CSF orexin-A levels were statistically different (p < 0.001) between AD (148.01 ± 29.49 pg/mL), NT1 (45.94 ± 13.63 pg/mL), NT2 (104.92 ± 25.55 pg/mL) and healthy subjects (145.18 ± 27.01 pg/mL). Moderate-severe AD patients (mini mental state examination < 21) showed the highest CSF orexin-A levels, whereas NT1 patients showed the lowest CSF orexin-A levels. Correlation between CSF levels of Aβ42 and orexin-A was found only in healthy subjects (r = 0.26; p = 0.01), and not in narcolepsy or AD patients. This lack of correlation in both diseases may be explained by the pathology itself since the correlation between these two biomarkers is evident only in the healthy subjects. This study adds to the present literature by further documenting the interplay between orexinergic neurotransmission and cerebral Aβ dynamics, possibly sustained by sleep.

OBJECTIVE: 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.