Symptoms Of Narcolepsy Research Articles

Experiences and beliefs related to sleep paralysis among the general population of the twin cities: A cross-sectional study

BackgroundSleep paralysis (SP) is a rapid eye movement (REM) parasomnia that occurs during the transition between wakefulness and sleep. During this brief state, a person is conscious but unable to move or speak, often experiencing hallucinations. It is ‘isolated’ when it occurs without other symptoms of narcolepsy or sleep disorders. Despite its prevalence, much remains unknown about its clinical features and associated beliefs. ObjectivesThis study examines the frequency of self-reported SP experiences and its associated demographic characteristics, along with participants' beliefs about the condition. MethodsA cross-sectional survey was conducted among visitors at a shopping mall, using the Unusual Sleep Experiences Questionnaire (USEQ) to assess the features of SP episodes and the common beliefs surrounding them. ResultsA total of 350 participants were surveyed (mean age = 25.5 ± 9.30 years; 55.4 % females). Participants who experienced SP at least once in their life time (39.1 %) reported feeling pressure on their chest (67.2 %), an inability to open their eyes (71.5 %), and difficulty speaking (81.0 %) during the episode. The majority of the individuals reported having their first episode at a young age (16–20 years). Most people (24.5 %) were unaware that this condition was known as sleep paralysis, and many (23.5 %) thought that it was just ‘a dream’. ConclusionIsolated sleep paralysis episodes are fairly prevalent, with many people experiencing their first episode at a young age. A typical episode entails a sense of pressure on the chest and difficulty in vocalizing. Misconceptions about the condition are common and wage further exploration.

Efficacy of once-nightly sodium oxybate (FT218) on daytime symptoms in individuals with narcolepsy with or without concomitant alerting agent use: A post hoc analysis from the phase 3 REST-ON trial

Objective/BackgroundExtended-release, once-nightly sodium oxybate (ON-SXB) significantly improved narcolepsy symptoms in participants in the phase 3, randomized, double-blind, placebo-controlled REST-ON trial. This post hoc analysis of REST-ON data evaluated ON-SXB efficacy in participants with or without concomitant alerting agent use. Patients/methodsParticipants with narcolepsy aged >16 years were randomized 1:1 to ON-SXB (week 1: 4.5 g, weeks 2–3: 6 g, weeks 4–8: 7.5 g, weeks 9–13: 9 g) or placebo. Primary endpoints in this post hoc analysis included change from baseline in mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement (CGI-I) rating, and number of weekly cataplexy episodes. The secondary endpoints were change from baseline in the Epworth Sleepiness Scale (ESS) score and in objective and subjective disrupted nighttime sleep parameters. Post hoc analyses assessed participants with and without alerting agent use across 6-, 7.5-, and 9-g doses. ResultsIn the modified intent-to-treat population, 119 (63 %) were (ON-SXB, n = 66; placebo, n = 53) and 71 (37 %) were not (ON-SXB, n = 31; placebo, n = 40) taking alerting agents. Regardless of alerting agent use, treatment with ON-SXB resulted in significant improvements vs placebo (all doses, P < 0.05) for MWT, CGI-I, and number of weekly cataplexy episodes. Significant improvements in ESS (all doses, P < 0.05) with ON-SXB vs placebo were observed in the alerting agent use cohort. Directional improvements in ESS were reported with all doses in the no alerting agent use group. ConclusionsRegardless of concomitant alerting agent use, ON-SXB improved daytime and nighttime narcolepsy symptoms vs placebo.

Improvements in daytime sleepiness and disrupted nighttime sleep with once-nightly sodium oxybate in people with narcolepsy type 1 and type 2: a plain language summary.

This is a plain language summary of a published article in the journal Sleep. Narcolepsy is a sleep condition that has 2 different subtypes: narcolepsy type 1 and narcolepsy type 2. These are called NT1 and NT2 for short. Sodium oxybate (SXB) is approved to treat excessive daytime sleepiness (EDS) and cataplexy. People with NT1 and NT2 both have EDS, but cataplexy is only present in people with NT1. Limited information is available about how SXB works in people with NT2. This is because previous trials have included only people with NT1 or people with unspecified narcolepsy. For more than 20years, the only available formulation of this medicine had to be given twice during the night. Many people with narcolepsy find that chronically waking up in the middle of the night for a second dose of SXB is disruptive to themselves or others in their household. People have also reported sleeping through alarm clocks, missing their second dose, and feeling worse the next day. Some people have accidentally taken the second dose too early, putting them at risk for serious adverse effects. These adverse effects may include slow breathing, low blood pressure, or sedation. The US Food and Drug Administration (FDA) approved a medicine called LUMRYZ™ (sodium oxybate) for extended-release oral suspension in May 2023. LUMRYZ is a once-nightly formulation of SXB (ON-SXB for short) and is taken as a single dose before bedtime. This medicine treats EDS and muscle weakness (also known as cataplexy) in people with narcolepsy. A clinical trial called REST-ON studied ON-SXB to find out if it was better at treating narcolepsy symptoms than a medicine with no active ingredients (placebo). This summary describes a study that tested whether ON-SXB was better than placebo at treating narcolepsy symptoms in people with NT1 or NT2. This study showed that compared to people who took placebo, people who took ON-SXB were able to stay awake longer during the day, felt less sleepy during the daytime, had less cataplexy, and had more improvements in their symptoms overall than people who took placebo. ON-SXB has been proven effective for people with NT1 or NT2. Unlike prior formulations of SXB, ON-SXB is taken once at bedtime, without requiring waking up in the middle of the night for a second dose.

Exploring the correlation between paediatric narcolepsy and serum neurofilament light chain levels: An exploratory study

BackgroundThe 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. MethodsThis 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. ResultsPatients 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). ConclusionThe 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.

Incidence of narcolepsy symptoms after taking COVID-19 vaccines: a Jordanian cross-sectional study.

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. 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. 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. 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.

The impact of narcolepsy symptoms and treatment on sex life - current evidence and reports

Introduction: Narcolepsy (NT) can manifest as excessive daytime sleepiness (EDS), cataplexy, hypnagogic (HHG) and hypnopompic (HHP) hallucinations, sleep paralysis, orgasmolepsy – all of which may affect patients' functioning. The aim of the study was to determine the impact of NT, specific sexual dysfunctions and drugs used in NT on sex life. Materials and methods: A narrative review was conducted, using keywords: narcolepsy, sexual dysfunctions, medications in narcolepsy from repository inception to March 17, 2024 searching PubMed/MEDLINE, Google Scholar, Crossref, Cochrane databases. The quality of the reviewed articles was assessed using the Scale for the Assessment of Narrative Review Articles (SANRA). Results: Sexual activity and satisfaction are reduced in up to 81.1% of patients. There are often multiple co-occurring autonomic dysregulations in patients, including the genitourinary system, causing sexual dysfunction (erectile dysfunction in 48% of men; vaginal lubrication in 81% of women). Orgasmolepsy negatively affects sexual and social relationships in more than 1⁄3 of respondents. Sleep paralysis can be accompanied by HHG, which often present the impression of sexual assault and harassment. They may cause anxiety, post-traumatic stress disorder (PTSD) features, depressed mood, in extreme cases leading to suicide attempts. Of the drugs used in NT, only methylphenidate can increase libido and reduce erectile dysfunction in NT. Conclusions: Orgasmolepsy, sexual and autonomic dysfunction in NT significantly reduce patients' quality of sex life. Sleep paralysis with sexual HHG can reduce psychological well-being. A holistic intervention approach, using behavioural interventions, cognitive-behavioural therapy, education of the patient and their loved ones, is crucial in the treatment of sexual difficulties. Keywords: narcolepsy, sexual dysfunctions, medications in narcolepsy

Development of the pediatric narcolepsy patient-reported outcomes scale (PN-PROs)

BackgroundPediatric narcolepsy is a chronic neurological disorder that impacts the health and overall wellbeing of children and adolescents with the disease. Meaningful and regular assessment of symptom frequency and severity is important for the long-term management of narcolepsy and for optimizing quality of life. However, there is currently no patient-reported outcomes (PROs) measure developed from both patient and expert input that is designed specifically to assess the impact of pediatric narcolepsy on daily life and overall disease burden.MethodsWe conducted a qualitative mixed-methods study to develop a novel patient-reported outcomes measure for pediatric narcolepsy patients. We created and refined a conceptual framework through literature review, semi-structured interviews with narcolepsy experts, and focus groups of children and adolescents with narcolepsy and their parents. Guided by the domains and facets identified in our conceptual framework and further literature review, we developed a PROs item bank. Our team further refined the item bank and classified items through team discussions and expert guidance. Content validity of the item pool was evaluated with expert review, readability analysis, and cognitive interviews with narcolepsy patients.ResultsThrough our processes, we developed a PROs item bank comprising two domains (narcolepsy symptoms and functional impairment) that contains 10 facets. The final item bank consists of 55 items, with 27 items representing five facets of narcolepsy symptoms (behavior, cataplexy, cognitive difficulties, sleep quality, and sleepiness) and 28 items representing five facets of functional impairment (bothered by/worried about symptom, cognitive/academic, global functioning, safety, and social).ConclusionWe developed items for the Pediatric Narcolepsy Patient-Reported Outcomes (PN-PROs) measure that incorporates expert insight, published literature, and testimony from children/adolescents living with narcolepsy and their families. Upon completion of the psychometric testing and content validation process, we believe the PN-PROs will provide a useful longitudinal measure of disease control and standardize outcome assessments in clinical practice and research studies.

Dosing Optimization of Low-Sodium Oxybate in Narcolepsy and Idiopathic Hypersomnia in Adults: Consensus Recommendations.

Low-sodium oxybate (LXB) is approved for treatment of narcolepsy in patients aged 7years and older and treatment of idiopathic hypersomnia in adults. LXB contains the same active moiety with 92% less sodium than sodium oxybate (SXB). As the indication for oxybate treatment in patients with idiopathic hypersomnia is new and allows for individualized dosing optimization, guidance for beginning LXB treatment is needed. In particular, clinicians may benefit from guidance regarding treatment initiation, dosing/regimen options, potential challenges, and treatment expectations. Additionally, pharmacokinetic profiles differ slightly between both treatments, and further guidance on transitioning from SXB to LXB in patients with narcolepsy may aid clinicians. An expert panel of five sleep specialists was convened to obtain consensus on recommendations for these topics using a modified Delphi process. Across two virtual meetings, the panel agreed on 31 recommendations with a high degree of consensus that fell into four overarching topics: (1) introducing LXB to patients; (2) initiating LXB for adult narcolepsy and idiopathic hypersomnia; (3) addressing challenges in using LXB; and (4) transitioning from SXB to LXB. The panel recommended that clinicians provide a clear overview of how LXB works for treating symptoms in narcolepsy or idiopathic hypersomnia, as appropriate for their patients, explain safety aspects, and set expectations prior to initiating LXB treatment. Strategies for initial dosing and regimen are provided. Strategies for adjusting the dose, regimen, timing, and consideration of individual factors were developed for specific instances in which patients may have trouble staying asleep or waking up, as well as guidance for addressing potential adverse events, such as nausea, dizziness, anxiety, and depression. Discussion points based on existing literature and clinical experience were included as relevant for each statement. Clinicians may use this resource to guide LXB dosing optimization with patients.

Effectiveness and optimization of low-sodium oxybate in participants with narcolepsy switching from a high-sodium oxybate: data from the Substitution of Equal Grams of Uninterrupted Xyrem to Xywav study.

Low-sodium oxybate (LXB; calcium, magnesium, potassium, and sodium oxybates; Xywav) contains the same active moiety as high-sodium oxybates (SXBs; SXB [Xyrem] and fixed-dose SXB [Lumryz]), with 92% less sodium, and is approved in the United States for treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy, and idiopathic hypersomnia in adults. Patients with narcolepsy have increased cardiovascular risk relative to people without narcolepsy. LXB's lower sodium content is recognized by the United States Food and Drug Administration in the narcolepsy population as clinically meaningful in reducing cardiovascular morbidity compared with SXBs. The Substitution of Equal Grams of Uninterrupted Xyrem to Xywav study (NCT04794491) examined the transition experience of patients with narcolepsy switching from SXB to LXB. Eligible participants were aged 18-80 years with narcolepsy type 1 or 2 on a stable SXB dose/regimen. After 2 weeks, participants transitioned gram-per-gram to LXB for 6 weeks, with opportunity for subsequent titration. Assessments included the Epworth Sleepiness Scale, Patient Global Impression of change, Ease of Switching Medication Scale, and Forced Preference Questionnaire. The study enrolled 62 participants at baseline; 60 transitioned to LXB and 54 completed the study. At baseline and end of the LXB intervention/early discontinuation, respectively, mean total doses were 8.0 and 8.0 g/night; mean Epworth Sleepiness Scale scores were 9.4 and 8.8. Most participants reported improvement (45%) or no change (48%) in narcolepsy symptoms on the Patient Global Impression of change, reported the transition to LXB was "easy" (easy, extremely easy, not difficult at all; 93%) on the Ease of Switching Medication Scale, and preferred LXB compared with SXB (79%) on the Forced Preference Questionnaire, most commonly due to the lower sodium content. Most participants switched from SXB to LXB with minimal modifications of dose/regimen and reported the transition process was easy. Effectiveness of oxybate treatment was maintained on LXB, and most participants preferred LXB to SXB. No new safety or tolerability issues were identified. Registry: ClinicalTrials.gov; Name: An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy; URL: https://classic.clinicaltrials.gov/ct2/show/NCT04794491; Identifier: NCT04794491. Macfadden W, Leary EB, Fuller DS, Kirby MT, Roy A. Effectiveness and optimization of low-sodium oxybate in participants with narcolepsy switching from a high-sodium oxybate: data from the Substitution of Equal Grams of Uninterrupted Xyrem to Xywav study. J Clin Sleep Med. 2024;20(9):1467-1477.

0645 Comparison of Demographics and Baseline Narcolepsy Symptoms Between Participants with NT1 and NT2 from REST-ON

0645 Comparison of Demographics and Baseline Narcolepsy Symptoms Between Participants with NT1 and NT2 from REST-ON

Effectiveness of an intervention program on physical activity in children with narcolepsy type 1

ObjectivesPhysical activity (PA) is recommended as part of the management of narcolepsy type 1 (NT1). This study aimed at 1) characterizing PA in children and adolescents treated for NT1 using objective and subjective measurements, 2) evaluating how PA is associated with NT1 symptoms and comorbidities, and 3) evaluating the effects of an Adapted Physical Activity (APA) program on PA and clinical characteristics. Patients/methodsPatients with NT1 from the National Reference Center of Narcolepsy (Lyon, France) were consecutively included in an APA intervention protocol. Narcolepsy symptoms and comorbidities were collected using standardized questionnaires and sustained attention was evaluated using the Bron-Lyon Attention Stability Test before and after the four-week APA intervention. PA was measured objectively using actigraphy throughout the study. ResultsTwenty-seven NT1 patients were included (median age 14.7 years [8.3–18.4], cataplexy 88.9%, obesity 37.0%). At baseline, 52.4% of the patients had satisfactory PA levels according to international recommendations. Patients with leisure-time PA (LTPA) showed higher quality of life than patients without. 45% of the patients increased PA during the intervention compared to baseline. These responsive patients had more depressive feelings and tended to have lower objective PA than non-responsive patients at baseline. No significant correlation was found between PA levels before and during the intervention and other clinical data. ConclusionsMost children with NT1 showed satisfying PA levels despite their daytime sleepiness. LTPA engagement was associated with higher quality of life. An APA intervention could be effective in children with narcolepsy, especially for those with depressive feelings.

Theory of Mind impairment in childhood narcolepsy type 1: a case-control study.

Narcolepsy type 1 is a central disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy and other rapid eye movement sleep-related manifestations. Neurophysiological studies suggest that narcolepsy type 1 patients may experience impairment in emotional processing due to structural and functional changes in limbic structures and associated areas. However, the only study exploring narcolepsy behavioural responses found no impairment in the ability to recognize emotions, possibly due to compensatory mechanisms. The present study was designed to fill this gap in the literature by investigating the behavioural impairment related to emotional processing focusing on an advanced socio-cognitive skill, namely Theory of Mind, in paediatric narcolepsy type 1 patients. Twenty-two narcolepsy type 1 children and adolescents (six female; age range: 8.0-13.5) and 22 healthy controls matched for age and sex (six female; age range: 8.9-13.0) underwent a neuropsychological evaluation to assess socio-economic status, verbal abilities, working memory, social anxiety and Theory of Mind via a verbal task (i.e. Strange Stories task) and a visual task (i.e. Silent Films). Narcolepsy type 1 patients were also evaluated for disease severity. Patients exhibited impairment in Theory of Mind skills, as assessed both through both verbal (controls median = 8; patients median = 5; P = 0.009) and visual tasks (controls median = 8; patients median = 6; P = 0.003), compared to healthy controls. Correlation analyses showed that verbal and visual Theory of Mind was negatively related to narcolepsy severity (ρ = -0.45, P = 0.035 and ρ = -0.52, P = 0.012), and daytime sleepiness (ρ = -0.48, P = 0.025 and ρ = -0.45, P = 0.038). Our study shows a selective impairment in the Theory of Mind domain in children and adolescents with narcolepsy type 1. In addition, our results highlight a link between symptom severity and Theory of Mind, suggesting that lower Theory of Mind levels are associated with higher symptom severity. Further, longitudinal studies are needed to disentangle the direction of this relation and to disambiguate if narcolepsy severity impaired children's Theory of Mind or if Theory of Mind skills modulate the severity of narcolepsy symptoms by providing a greater ability to avoid cataplexy.

Sex disparities in clinical features and burden of narcolepsy type 1.

To investigate potential sex-related differences in patients with narcolepsy type 1, we carried out an analysis of baseline data from 93 women and 89 men with narcolepsy type 1 who participated in the TElemedicine for NARcolepsy (TENAR) trial. The following data were considered: sociodemographics; diagnostic (disease history, polysomnography, orexin, human leukocyte antigen) and clinical features, including sleepiness (Epworth Sleepiness Scale), cataplexy and other narcolepsy symptoms; disease severity (Narcolepsy Severity Scale); pharmacological treatment; depressive symptoms (Beck Depression Inventory); and self-reported relevance of eight narcolepsy-related issues. We found that, compared with men, significantly more women reported automatic behaviours (55.4% versus 40%) and had higher Epworth Sleepiness Scale (median 10 versus 9) and Beck Depression Inventory scores (median 10.5 versus 5), and there was a trend for a higher Narcolepsy Severity Scale total score in women (median 19 versus 18, p = 0.057). More women than men were officially recognized as having a disability (38% versus 22.5%) and considered 5/8 narcolepsy-related issues investigated as a relevant problem. More severe sleepiness and a greater narcolepsy-related burden in women could mirror sex differences present in the general population, or may be related to suboptimal management of narcolepsy type 1 or to more severe depressive symptoms in women. Future studies and guidelines should address these aspects.

Creation of a shortened version of the Sleep Disorders Questionnaire (SDQ).

The 176-item Sleep Disorders Questionnaire (SDQ) was initially developed using canonical discriminant function analysis on 4 groups of sleep disorder patients, but it was never studied by factor analysis in its entirety. Several authors have criticized 2 of its subscales as being confounded with each other, and its narcolepsy scale as substantially over-diagnosing narcolepsy. This study describes its first exploratory factor analysis (EFA), the intent of which was to reassess item membership on the 4 existing subscales and to derive new scales to improve differential diagnosis between patient groups. It was also hoped that EFA could reduce the total number of questions, to increase speed of completion. The EFA was performed on the anonymized SDQ results from a retrospective review of the charts of 2131 persons from 7 sleep disorders clinics and research centers. Factors were assessed via scree plots and eigenvalues. The EFA identified four main factors: insomnia, daytime sleepiness, substance use, and sleep-disordered breathing. The insomnia factor had 3 subfactors: psychological symptoms of insomnia, subjective description of insomnia, and insomnia due to periodic limb movements. The sleepiness factor had two subfactors: daytime sleepiness and neurological symptoms of narcolepsy. The novel substance use factor was homogeneous, as was the sleep-disordered breathing factor. Importantly, the EFA reassigned items from the original SDQ's NAR, PSY, and PLM subscales to five of the new subscales. The Sleep Apnea (SA) subscale emerged mostly unchanged. The 7 resulting factors comprised only 66 items of the original 176-item SDQ. These results have allowed the creation of a new shorter questionnaire, to be called the SDQ-2. External validation of the SDQ-2 is currently underway. It will likely prove to be a superior differential diagnostic instrument for sleep disorders clinics, compared to the original SDQ.

Diagnosis and symptoms of narcolepsy from the patient perspective: results from in-depth qualitative interviews

Diagnosis and symptoms of narcolepsy from the patient perspective: results from in-depth qualitative interviews

Application of AASM clinical significance thresholds to once-nightly sodium oxybate for improvement in narcolepsy symptoms

Application of AASM clinical significance thresholds to once-nightly sodium oxybate for improvement in narcolepsy symptoms

Comparison of demographics and baseline narcolepsy symptoms between participants with NT1 and NT2 from the Phase 3 REST-ON clinical trial

Comparison of demographics and baseline narcolepsy symptoms between participants with NT1 and NT2 from the Phase 3 REST-ON clinical trial

Bi-allelic variants in HCRT cause autosomal recessive narcolepsy.

Narcolepsy with cataplexy is a complex disease with both genetic and environmental risk factors. To gain further insight into the homozygous HCRT-related narcolepsy, we present a case series of five patients from two consanguineous families, each harboring a novel homozygous variant of HCRT c.17_18del. All affected individuals exhibited severe cataplexy accompanied by narcolepsy symptoms during infancy. Additionally, cataplexy symptoms improved or disappeared in the majority of patients over time. Pathogenic variants in HCRT cause autosomal recessive narcolepsy with cataplexy. Genetic testing of the HCRT gene should be conducted in specific subgroups of narcolepsy, particularly those with early onset, familial cases, and a predominantly cataplexy phenotype.

Disrupted topological properties of structural brain networks present a glutamatergic neuropathophysiology in people with narcolepsy.

Growing evidences have documented various abnormalities of the white matter bundles in people with narcolepsy. We sought to evaluate topological properties of brain structural networks, and their association with symptoms and neuropathophysiological features in people with narcolepsy. Diffusion tensor imaging was conducted for people with narcolepsy (n = 30) and matched healthy controls as well as symptoms assessment. Structural connectivity for each participant was generated to analyze global and regional topological properties and their correlations with narcoleptic features. Further human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. A wide and dramatic decrease in structural connectivities was observed in people with narcolepsy, with descending network degree and global efficiency. These metrics were not only correlated with sleep latency and awakening features, but also reflected alterations of sleep macrostructure in people with narcolepsy. Network-based statistics identified a small hyperenhanced subnetwork of cingulate gyrus that was closely related to rapid eye movement sleep behavior disorder (RBD) in narcolepsy. Further imaging genetics analysis suggested glutamatergic signatures were responsible for the preferential vulnerability of connectivity alterations in people with narcolepsy, while additional PET/SPECT data verified that structural alteration was significantly correlated with metabotropic glutamate receptor 5 (mGlutR5) and N-methyl-D-aspartate receptor (NMDA). People with narcolepsy endured a remarkable decrease in the structural architecture, which was not only closely related to narcolepsy symptoms but also glutamatergic signatures.

Prevalence and incidence of narcolepsy symptoms in the US general population

ObjectiveThe objectives of this study are to evaluate the prevalence and incidence of Narcolepsy type 1 and type 2 and to determine the prevalence of narcolepsy diagnosis criteria in the US general population. MethodsThis longitudinal study was conducted in the adult US general population in two occasions. The initial interviews included 15 states (Arizona, California, Colorado, Florida, Idaho, Missouri, New York, North Carolina, North Dakota, Oregon, Pennsylvania, South Dakota, Texas, Washington, and Wyoming). The follow-up interviews, was done three years later in eight of these states. Of the 19,136 contacted individuals, 15,929 completed the initial interview and 10,931 completed the follow-up. Participants were interviewed using the Sleep-EVAL system, an artificial intelligence tool. Narcolepsy Type 1 (with cataplexy) and Narcolepsy Type 2 (without cataplexy) were defined according to the ICSD-3 classification. Symptoms of narcolepsy were assessed by frequency per week and duration. Medical visits and diagnoses were also collected. ResultsParticipants were aged between 18 and 102 years of age (mean 45.8 ± 17.9 years), 51.3 % were women. The prevalence of narcolepsy with cataplexy was 12.6 per 100,000 individuals (95 % C.I., 0 to 30) and narcolepsy without cataplexy was 25.1 per 100,000. The incidence per year was 2.6 per 100,000 individuals (95 % C.I., 0 to 11). ConclusionsNarcolepsy is a rare condition affecting 37.7/100,000 individuals (126,191 individuals in the current US population). Our US general population prevalence is in line with rates found in community-based studies but lower than what is reported in claim database studies.