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Background: Lower-sodium oxybate (LXB) is an oxybate medication with the same active moiety as sodium oxybate (SXB) and a unique composition of cations, resulting in 92% less sodium. LXB was shown to improve cataplexy and excessive daytime sleepiness in people with narcolepsy in a placebo-controlled, double-blind, randomized withdrawal study (NCT03030599). Additional analyses of data from this study were conducted to explore the effects of LXB on cataplexy, including the clinical course and feasibility of transition from other anticataplectics to LXB monotherapy., Objective: The aim of these analyses was to evaluate cataplexy frequency during initiation/optimization of LXB and taper/discontinuation of prior antidepressant/anticataplectic medications., Methods: Eligible participants (adults aged 18-70 years with narcolepsy with cataplexy) entered the study taking SXB only (group A), SXB + other anticataplectics (group B), or anticataplectic medication other than SXB (group C), or were cataplexy-treatment naive (group D). LXB was initiated/optimized during a 12-week, open-label, optimized treatment and titration period (OLOTTP). Other anticataplectics were tapered/discontinued during weeks 3-10 of OLOTTP. A 2-week stable-dose period (SDP; during which participants took a stable dose of open-label LXB) and 2-week double-blind randomized withdrawal period (during which participants were randomized to continue LXB treatment or switch to placebo) followed OLOTTP. Treatment-emergent adverse events (TEAEs) were recorded throughout the duration of the study., Results: At the beginning of OLOTTP, median weekly cataplexy attacks were lower in participants taking SXB at study entry (SXB only [2.00]; SXB + other anticataplectics [0.58]) versus participants who were taking other anticataplectics (3.50) or were anticataplectic naive (5.83). Median weekly cataplexy attacks decreased during weeks 1-2 of OLOTTP in all groups. Increased cataplexy frequency was observed in participants tapering/discontinuing other anticataplectics during weeks 3-10 and was more prominent in participants taking other anticataplectics alone compared with those taking SXB plus other anticataplectics. Cataplexy frequency decreased throughout initiation/optimization in anticataplectic-naive participants. Median number of cataplexy-free days/week at the end of SDP (study week 14) was similar in all groups (6.0, 6.1, 6.0, and 6.2 in groups A, B, C, and D, respectively). During OLOTTP and SDP, TEAEs of worsening cataplexy were reported in 0%, 47.8%, 16.7%, and 2.2% of participants in groups A, B, C, and D, respectively; most TEAEs of worsening cataplexy were reported during tapering/discontinuation of other anticataplectics., Conclusions: LXB monotherapy was effective in reducing cataplexy and increasing cataplexy-free days. These results illustrate the feasibility of switching from SXB to LXB while tapering/discontinuing other anticataplectics., Trial Registration: A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy; https://clinicaltrials.gov/ct2/show/NCT03030599 ; clinicaltrials.gov identifier: NCT03030599., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In order to clarify the difference in clinical characteristics between narcolepsy-like hypersomnia without cataplexy, which is called essential hypersomnia syndrome (EHS), and narcolepsy, we compared background variables, symptoms and treatment outcomes between 19 EHS patients and 20 narcoleptic patients. The results indicated significantly milder rapid eye movement (REM)-related symptoms, longer sleep latencies on multiple sleep latency test and smaller dosages of psycho-stimulants for suppressing daytime sleepiness in EHS than in narcolepsy. Positive findings of HLA-DQB1*0602 were recognized in less than 40% of EHS patients. We speculated that EHS would form a subgroup of hypersomnia in which disease severity is milder, and treatment response is better than typical narcolepsy. [ABSTRACT FROM AUTHOR]

Background: Narcolepsy impacts quality of life (QoL) with its symptomatology in hobbies and everyday activities, work and productivity and has social and economic consequences. The aim of this review is to map and synthesize evidence about QoL in narcolepsy patients and to focus on research strategies and publications in the matter., Methods: A scoping review of articles published between 2014-2025. The initial search of WoS resulted in 7748 articles and 2583 in PubMed being screened for eligibility. Intervention, comorbidity, non-narcolepsy, prevalence and medical trials studies were excluded. We extracted data on bibliometric characteristics, research questions, sample and recruitment method, design, concepts and measures, and the main findings. Two independent reviewers did the screening and analyses. The analyzed data were consulted on with stakeholders to settle gaps, possibilities and directions for future research. This study followed the PRISMA-ScR guidelines., Results: Twenty papers were included in this study. There is an increasing trend in publishing studies focused on QoL in narcolepsy patients, but its spread is very limited across various audiences. Most of the studies assess the association of narcolepsy symptoms, treatment, mental health or nutritional status and QoL in narcolepsy patients. Most used was a questionnaire-based cross-sectional design comparing a control group vs narcolepsy patients recruited through regular follow up at a sleep clinic or national reference centers or patients' organization., Conclusion: There is a need to spread knowledge beyond the neurology audience, to widen the scope of research beyond the burden of the symptoms and to employ explorative qualitative designs., Competing Interests: Declarations. Ethical standards: This work did not include patients and only worked with previously published articles. Conflict of interest: Each author states that all relevant financial or non-financial, any personal or professional relationships with other people or organizations that could pose a conflict of interests or that could influence or bias this manuscript have been fully disclosed., (© 2025. The Author(s).)

Study Objective: Sleep is traditionally scored using 30-s epochs of polysomnographies. As sleep is physiologically dynamic and 30-s epochs may conceal important characteristics, we aim to challenge this standard by scoring sleep in 5-s mini-epochs and analyzing inter-rater variability between human and automatic scorers., Methods: In 40 polysomnography recordings, 120 mini-epochs per polysomnography were scored manually by three human experts (expert1_5s, expert2_5s and expert3_5s) and automatically by a validated sleep classifier (USleep_5s). Additionally, 5-s mini-epochs (clinical_5s) extracted from conventional human-scored 30-s epochs were considered. We assessed inter-rater variability and stage shifting in epochs and mini-epochs and further in narcolepsy type 1 (NT1) patients and siblings., Results: Agreement for mini-epochs was κ = 0.50 ± 0.11 (expert1_5s vs clinical_5s) and κ = 0.51 ± 0.12, (expert1_5s vs USleep_5s). Between human experts, agreement was κ = 0.51 ± 0.16 (expert1_5s vs expert2_5s), and κ = 0.57 ± 0.11 (expert1_5s vs expert3_5s). Stage shift percentages were significantly higher in mini-epochs scored by expert1_5s (27.75 %) and USleep_5s (22.88 %) than corresponding conventional epochs (5.12 %), with no significant difference between NT1 patients and siblings., Conclusion: While mini-epoch scoring agreement was generally high, it was still lower than within epochs, likely due to a lack of standard mini-epoch scoring procedure and the automatic classifier being trained on epochs. However, stage discrepancies between epochs and mini-epochs and increased stage shifting in mini-epochs support that epochs can contain several stages, and that mini-epochs could supplement more detailed sleep characterization potentially enabling more precise diagnosis and finding new polysomnographic biomarkers. Future studies should include larger datasets to refine mini-epoch scoring rules and exploit automatic classifiers e.g. via transfer learning., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.K.H. has been an expert consultant for the Norwegian state but reports no other non-financial. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Currently, diagnosing narcolepsy and idiopathic hypersomnia (IH) in subjectively sleepy children requires an overnight polysomnographic sleep study followed by a daytime multiple sleep latency test (MSLT). We aimed to compare sleep macro-architecture to identify differences between these groups., Methods: All children referred for a MSLT between May 2010 to December 2023 whose parent consented for their data be used in research were eligible. Each child was age- and sex-matched to a control. Sleep stability was defined as the maintenance of a particular sleep stage before waking or transitioning to another sleep state. As a measure of sleep disturbance, the number and duration of bouts of each sleep stage was recorded., Results: 28 children with Narcolepsy, 11 with IH and 26 with subjective sleepiness were included. Children with narcolepsy exhibited higher numbers of transitions to wake after sleep onset compared to their controls and to the subjectively sleepy group (p < 0.001 for both). The number of REM bouts was greater in the narcolepsy group compared to their control group (p < 0.001), the IH group (p < 0.05) and the subjectively sleepy group (p < 0.05), while the average duration of REM bouts was shorter in the narcolepsy group compared to both the IH group (p < 0.05) and subjectively sleepy group (p < 0.05). Mean sleep latency on the MSLT was correlated with a number of polysomnographic variables., Conclusions: Our study suggests that specific sleep architecture patterns could potentially serve as diagnostic biomarkers for distinguishing paediatric narcolepsy from those with IH and those with a non-diagnostic MSLT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To assesses the prevalence and co-occurrence of anxiety, depressive symptoms, suicidal thoughts, and hopelessness in patients with narcolepsy type 1 (NT1)., Patients/methods: In this cross-sectional study, 127 patients with NT1 (mean age 38.2 ± 15.5 years, 53.5 % female) and 131 controls (mean age 37.4 ± 14.3 years, 59.5 % female) matched for age, sex, and education, filled in the following validated questionnaires: Beck Depression Inventory-II (BDI), State-Trait Anxiety Inventory (STAI), and Beck Hopelessness Scale (BHS). Comparisons between groups and multivariable logistic regression analyses were performed., Results: Patients with NT1 presented significantly higher scores in BDI, suicidal thoughts (BDI-item-9), STAI-trait, STAI-state, and BHS than controls. Adjusted for age, sex, and educational level, NT1 was significantly associated with depressive symptoms (BDI≥13; OR 3.23, 95%CI 1.71-6.10), trait anxiety symptoms (STAI-trait≥38; OR 1.91, 95%CI 1.14-3.21), co-occurrence of BDI≥13 with STAI-trait≥38 (OR 2.72, 95%CI 1.47-5.05), and with STAI-state≥38 (OR 2.24, 95%CI 1.17-4.30), and moderate to severe hopelessness (BHS≥9; OR 2.95, 95%CI 1.55-5.63)., Conclusions: Patients with NT1 present a multidimensional psychiatric burden and comorbidity between symptoms of depression and anxiety and suicidal thoughts, a concern that deserves tailored interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giuseppe Plazzi reports a relationship with Jazz Pharmaceuticals that includes: board membership. Giuseppe Plazzi reports a relationship with Bioprojet that includes: board membership. Giuseppe Plazzi reports a relationship with Centessa Pharmaceuticals, LLC that includes: board membership. Giuseppe Plazzi reports a relationship with Takeda Pharmaceutical Company Limited that includes: board membership. Giuseppe Plazzi reports a relationship with Idorsia Pharmaceuticals Ltd that includes: board membership. Fabio Pizza reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory. Fabio Pizza reports a relationship with Jazz Pharmaceuticals Inc that includes: speaking and lecture fees. Fabio Pizza reports a relationship with Bioprojet that includes: travel reimbursement. Elena Antelmi reports a relationship with Bioprojet that includes: speaking and lecture fees and travel reimbursement. Elena Antelmi reports a relationship with Jazz Pharmaceuticals Inc that includes: speaking and lecture fees and travel reimbursement. Elena Antelmi reports a relationship with Polifarma that includes: speaking and lecture fees. Francesco Biscarini reports a relationship with Bioprojet that includes: travel reimbursement. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background and Purpose: Narcolepsy is a chronic illness characterized by excessive daytime sleepiness and cataplexy. Recently, sodium oxybate (SXB) has been the only effective drug in treating multiple symptoms of narcolepsy. Our study aims to assess the effectiveness and safety of SXB in treating narcolepsy., Method: We searched four databases for eligible studies. Our primary outcome was to investigate the effectiveness of SXB through symptom improvement. For the secondary outcome, we assess its safety through the reported adverse events., Result: Five RCTs were included. The SXB group had significantly improved weekly cataplexy attacks better than the placebo (MD = -5.04, 95% CI [-6.35, -3.72], P < 0.00001), also the improvement in the Maintenance of Wakefulness Test, and ESS was better in the SXB group with (MD = 4.66, 95% CI: [2.24, 7.07], p = 0.0002), (MD = -1.93, 95% CI: [-2.73, -1.13], p < 0.00001) respectively. CGI-I was observed to be significantly better in the SXB group with (RR = 2.15, 95% CI: [1.69, 2.73], p < 0.00001). The weekly cataplexy attack was significantly improved by the doses (4.5, 6, and 9 gm) in comparison with the placebo, with the 9-gm dose having the most beneficial effect. The improvements were significant only in SXB 9 gm in ESS and 6 and 9 gm in CGI-I., Conclusion: SXB is an effective pharmacological treatment for the management of narcoleptic patients with cataplexy with an acceptable safety profile. Further studies with a large scale are needed to investigate and prove the efficacy and tolerability of SXB., Competing Interests: Declarations. Ethical approval and consent to participate: This study is a systematic review and meta-analysis that did not require ethical approval, as it did not involve the direct participation of individuals who would provide informed consent. Consent to publication: Consent to publication is not applicable in this case since this study is not a primary research study but rather a review and analysis of existing literature. Previous publication: We declare that this research paper has not been published elsewhere in any other academic journal or platform. Generative AI in scientific writing: We declare that we have not used AI in writing any part of this manuscript. Conflict of interest: No conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Study Objectives: The purpose of this study was to investigate the effects of neck myoclonus (NM) on sleep quality and daytime sleepiness in patients with narcolepsy (NT) and to further explore possible underlying mechanisms., Methods: We included 72 patients with narcolepsy type 1 (NT1), 34 patients with narcolepsy type 2 (NT2) and 33 healthy controls. Patients underwent questionnaires, lumbar puncture procedure, polysomnography, and multiple sleep latency test (MSLT). Healthy controls underwent polysomnography and questionnaires. Orexin-A levels in the cerebrospinal fluid (CSF) were analyzed by radioimmunoassay. Three catecholamines, including dopamine, norepinephrine and epinephrine, in the CSF were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)., Results: Both the NT1 and NT2 groups displayed a higher level of NM incidence rate and index compared to the control group in PSG. NT1 displayed greater MSLT REM--NM incidence rate and index than NT2. NM were often associated with arousal or awakening and body movements, which had a prominent influence on sleep quality in both narcoleptic patients and controls. There was a positive correlation between the NM index and the Pittsburgh Sleep Quality Index (PSQI), Stanford Sleepiness Scale (SSS) and Ullanlinna Narcolepsy Scale (UNS) scores in NT1 patients. In MSLT of NT1 patients, REM-NM index were positively correlated with the CSF dopamine levels, and there were elevated dopamine levels but reduced orexin-A levels in patients with REM-NM., Conclusion: NM incidence rate and index were high in patients with narcolepsy, which had a huge effect on sleep quality and aggravated daytime sleepiness. NM should be considered pathological and viewed as a new sleep-related movement disorder. Orexin-A and dopamine may be involved in the development of NM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Narcolepsy is a rare neurological disease caused by dysfunction of hypocretin-producing neurons. Hypocretin concentrations in the cerebrospinal fluid (CSF) of less than 110 pg/ml are considered pathological in adults., Objectives: To compare hypocretin levels of children with narcolepsy type 1, type 2 and disease control groups, in addition to a detailed CSF analysis, clinical and polysomnographic parameters., Methods: In a retrospective, cross-sectional study, children diagnosed with narcolepsy based on clinical and polysomnographic parameters, who received a CSF analysis and hypocretin measurement, in addition to controls, were included. CSF was analyzed for the presence of cells, total protein, lactate, intrathecal synthesis of antibodies against measles, rubella and/or varicella zoster, and oligoclonal bands. All children had a complete sleep study including a multiple sleep latency test (MSLT)., Results: 49 children with narcolepsy type 1, 15 children with type 2 and 37 children with other (suspected) neurological diseases were included. CSF routine analysis did not reveal any differences between the three groups. All children with narcolepsy type 1 had hypocretin levels of less than 110 pg/ml (range: 10-101 pg/ml). Hypocretin levels in type 2 patients ranged from 43 to 436 pg/ml (median 157 pg/ml). The median hypocretin level in the control cohort was 365 pg/ml (range: 153-583 pg/ml). In 4 children with narcolepsy type 2 the diagnosis was changed to narcolepsy level 1 because of a CSF hypocretin level of less than 110 pg/ml according to the recently proposed criteria, which consider the measurement of hypocretin in CSF., Conclusion: Children with narcolepsy type 1 showed significantly lower CSF hypocretin levels than children with narcolepsy type 2 and controls. As suggested by the recently published narcolepsy criteria, hypocretin levels of less than 110 pg/ml should be used as an additional criterion for the presence of narcolepsy type 1 in children., Competing Interests: Declaration of competing interest M.Otto received research support from the EU Joint Programm neurodegenerative diseases networks Genfi-Prox, the EU (MOOD-MARKER), the German Research Foundation/DFG (SFB1279), the foundation of the state Baden-Württemberg D.3830), Boehringer Ingelheim Ulm University BioCenter (D.5009) and the Thierry Latran Foundation. M. Otto gave scientific advice to Roche, Biogen, Axon, and Fujirebio. K.Rostasy received honoraria from UCB, Horizon, and Euroimmun, and serves as Consultant for Roche in the Operetta2 trial. A.Bertolini received travel funds from Octapharma, honoraria for the advisory board through Horizon. E.Wendel received travel funds from UCB. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

The article presents several research papers related to medicine. One paper discusses how respiratory events in Obstructive Sleep Apnea (OSA) end without Cortical Arousal. Another research is on sleepiness and information processing among individuals with narcolepsy. Another study discusses how chronic insomnia can be treated through light therapy.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Narcolepsy with cataplexy (NT1) is a rare hypothalamic disorder that presents with a dysregulation of the sleep-wake cycle (i.e., excessive daytime sleepiness and sleep and cataplectic attacks) and other motor, cognitive, psychiatric, metabolic, and autonomic disturbances, with putative autoimmune pathogenesis. Pediatric acute-onset neuropsychiatric syndrome (PANS) is a clinically heterogeneous disorder that presents with acute-onset obsessive-compulsive symptoms and/or a severe eating restriction, with concomitant cognitive, behavioral, or affective symptoms caused by infections and other environmental triggers provoking an inflammatory brain response, which evolves into a chronic or progressive neuroimmune disorder. In this study, we present the case of a 13-year-old boy with vocal tics and syncopal-like episodes, eventually diagnosed as NT1 and PANS, and from this we discuss the hypothesis that both NT1 and PANS might belong to the same immunological spectrum, resulting in comparable imbalances in key neurotransmitter axes (i.e., orexinergic and dopaminergic), with conceptual and operational implications, especially with regards to the pharmacological tretament., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PATRIZIA CONGIU reports financial support was provided by Fidia Farmaceutici S.p.a. PATRIZIA CONGIU reports financial support was provided by Pandas Italia ODV. PATRIZIA CONGIU reports financial support was provided by Fondazione di Sardegna. Professor Giuseppe Plazzi is part of the editorial board of Sleep Medicine journal If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Optimal measurement tools for problematic sleep inertia, common in some central disorders of hypersomnolence (CDH), have not yet been determined. We evaluated the performance of the Sleep Inertia Questionnaire (SIQ) in CDH, and how well it distinguished hypersomnolent groups from controls, and IH (idiopathic hypersomnia) from narcolepsy type 1 (NT1)., Methods: This prospective, bi-centric study included 63 control, 84 IH, 16 NT1, 18 narcolepsy type 2 (NT2), and 88 subjective excessive daytime sleepiness (sEDS) participants, using ICSD-3 criteria. 126 (47.2 %) participants were on any medication at the time of SIQ completion. We assessed construct validity of SIQ scores, and sleep inertia duration (SID), and compared them across diagnoses, controlling for age and center. We derived cutpoints to distinguish hypersomnolent patients from controls and IH from NT1. Sensitivity analyses for depression, chronotype, and medication were performed., Results: The SIQ sum and composite score were significantly lower in controls than in other groups (p < 0.0001), demonstrating outstanding ability to distinguish patients from controls (AUCs 0.92), without differences among hypersomnolent groups. SID (AUC 0.76) was significantly shorter in controls than in all hypersomnolent groups except NT1, and was shorter in NT1 than in IH or sEDS. Optimal SIQ sum cutpoint was 42 (J = 0.71) for patients versus controls. Optimal SID cutpoint in distinguishing IH from NT1 was 25 min (J = 0.39)., Conclusion: The SIQ has excellent ability to distinguish hypersomnolent patients from healthy controls, after controlling for depression, eveningness, and medication. SID is best at distinguishing IH from NT1., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Lynn Marie Trotti reports financial support was provided by National Institutes of Health. David T. Plante reports financial support was provided by American Academy of Sleep Medicine Foundation. Dr. Lynn Marie Trotti reports a relationship with American Academy of Sleep Medicine Foundation that includes: board membership and funding grants. Lynn Marie Trotti reports a relationship with American Academy of Sleep Medicine that includes: board membership, speaking and lecture fees, and travel reimbursement. Lynn Marie Trotti reports a relationship with American Board of Sleep Medicine that includes: board membership. Lynn Marie Trotti reports a relationship with Sleep Research Society that includes: speaking and lecture fees. Lynn Marie Trotti reports a relationship with CHEST that includes: speaking and lecture fees and travel reimbursement. Lynn Marie Trotti reports a relationship with Haymarket Medical Education that includes: speaking and lecture fees and travel reimbursement. Lynn Marie Trotti reports a relationship with Per CME that includes: speaking and lecture fees and travel reimbursement. Lynn Marie Trotti reports a relationship with Efficient CME that includes: speaking and lecture fees. Lynn Marie Trotti reports a relationship with Clinical Care Options LLC that includes: speaking and lecture fees and travel reimbursement. David T. Plante reports a relationship with National Institutes of Health that includes: funding grants. David T. Plante reports a relationship with Wisconsin Alumni Research Foundation Inc that includes: funding grants. David T. Plante reports a relationship with Harmony Biosciences that includes: consulting or advisory and funding grants. David T. Plante reports a relationship with Alzheimer's Association that includes: funding grants. David T. Plante reports a relationship with Jazz Pharmaceuticals Inc that includes: consulting or advisory. David T. Plante reports a relationship with Aditium Biosci that includes: consulting or advisory. David T. Plante reports a relationship with Alkermes that includes: consulting or advisory. David T. Plante reports a relationship with Teva Pharmaceutical Australia that includes: consulting or advisory. David T. Plante reports a relationship with American Academy of Sleep Medicine that includes: speaking and lecture fees. David Rye reports a relationship with National Institutes of Health that includes: funding grants. David T. Plante reports a relationship with NextSense that includes: funding grants. David Rye reports a relationship with Jazz Pharmaceuticals Inc that includes: consulting or advisory. David Rye reports a relationship with Takeda that includes: consulting or advisory. Ana Maria Vascan reports a relationship with National Institutes of Health that includes: funding grants. Ana Maria Vascan reports a relationship with Wisconsin Alumni Research Foundation Inc that includes: funding grants. Ana Maria Vascan reports a relationship with NASA that includes: funding grants. Prabhjyot Saini reports a relationship with NextSense that includes: consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Royalty from Cambridge University Press to David T. Plante. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Introduction: 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/m 2 ; 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)., Conclusion: 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

β-amyloid 42 (Aβ 42 ) 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 Aβ 42 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 Aβ 42 , total-tau, phosphorylated-tau, and orexin-A were assessed. The results showed that CSF levels of Aβ 42 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 Aβ 42 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Symptoms of depression and anxiety are common complications of narcolepsy. Earlier studies have shown that narcolepsy type 1 (NT1) is an autoimmune inflammatory disease and symptoms of depression and anxiety are closely related to fluctuations in inflammatory cytokines. The objective of the current research was to investigate the potential correlation between cytokines and symptoms of depression and anxiety in patients with NT1., Methods: We collected demographic and clinical data and information on cytokine levels from 50 patients with NT1 and used Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) to assess the severity of depression and anxiety symptoms. Patients with SDS scores ≥ 53 points were defined as depressive narcolepsy type 1 (D-NT1) and those with SDS scores < 53 points as non-depressive narcolepsy type 1 (ND-NT1). Patients with SAS scores ≥ 50 points were defined as anxious narcolepsy type 1 (A-NT1) and those with SAS scores < 50 points as non-anxious narcolepsy type 1 (NA-NT1). A binary logistic regression model was employed to identify the influencing factors of depressive and anxiety symptoms., Results: Levels of IL-10 (p = 0.02), IL-4 (p = 0.049) and disease duration (p = 0.049) were decreased, while SAS scores (p < 0.001) and total sleep duration (p = 0.03) were increased in D-NT1 relative to ND-NT1 patients. A-NT1 patients had higher SDS scores (p < 0.001) compared to NA-NT1 patients. Binary logistic regression analysis revealed associations of longer disease duration (OR=0.83; 95 % CI: 0.70-0.97) and increased IL-10 (OR=0.40; 95 % CI: 0.17-0.90) with reduced risk of depression and worsening anxiety (SAS score; OR=1.17; 95 % CI: 1.06-1.30) with increased risk of depression in patients with NT1. Consistently, worsening depression (SDS score; OR=1.22; 95 % CI: 1.07-1.39) was correlated with increased risk of anxiety in the NT1 group., Conclusion: Our finding that higher IL-10 levels correlate with a lower risk of depression in NT1 patients provides a reference for further exploration of the pathophysiological mechanisms of depressive symptoms in NT1 patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Patients with narcolepsy often experience disturbed nighttime sleep. Modafinil is commonly prescribed for hypersomnolence, but its impacts on nocturnal sleep remain unclear. This study uses actigraphy to examine the effect of modafinil on both hypersomnolence and nocturnal sleep patterns in patients with narcolepsy., Methods: Prior to treatment, 87 patients with narcolepsy wore an actigraphy for 7-14 days to assess their nighttime sleep. After evaluation, they received a daily dose of 200-400 mg of modafinil in the morning and wore an actigraphy again six months after initiating treatment. Questionnaires, including the Epworth-Sleepiness-Scale (ESS), the Visual-Analogue-for-Hypersomnolence (VAS), and the Short-Form-36-Health-Survey (SF-36), were used to evaluate hypersomnolence and quality of life both before and after treatment. Paired t-tests and independent samples t-tests were used for pre- and post-treatment comparisons and subgroup analysis. We used the Pearson's correlation test to measure the correlations between the sleep parameters of the actigraphy and data of the questionnaires., Results: Improvements in hypersomnolence were noted following modafinil treatment, and we observed no significant deterioration in nocturnal sleep parameters by the actigraphy. The total number of awakenings by actigraphy significantly decreased (p = 0.005), especially in females (p = 0.008), while sleep onset latency significantly increased in children/adolescents (p = 0.014). Correlations were found between the sleep parameters of the actigraphy and ESS, VAS, and SF-36 scores., Conclusion: Modafinil treatment may not worsen nighttime sleep in patients with narcolepsy. However, it should be administered with care in children and adolescents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Narcolepsy, a rare neurological disorder believed to have an autoimmune etiology, necessitates lifelong management. This study aimed to provide evidence supporting the safety of pharmacological treatment for narcolepsy. Methods: Five-year data on pitolisant, sodium oxybate, solriamfetol, and modafinil were extracted from the FDA Adverse Event Reporting System (FAERS) self-reporting database for the period spanning from 2019 to 2023. Various statistical methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network analysis (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed to quantify the signals. Finally, a comparative analysis was conducted between demographic data, outcomes, and inherent associations among the medications and the signals. Results: After data analysis, we obtained 50 signals (a cumulative count of 762 cases) for pitolisant, 640 signals (corresponding to 46,962 cases) for sodium oxybate, 40 signals (equivalent to 1,228 cases) for solriamfetol, and finally, 72 signals (representing 632 cases) for modafinil. The majority of these patients were female. Psychiatric and nervous system disorders were identified as the predominant adverse drug events (ADEs). For sodium oxybate, it is crucial to consider psychiatric disorders (such as suicidal ideation), respiratory disorders (including sleep apnea syndrome and respiratory depression), and signs of pregnancy and congenital familial diseases. For solriamfetol, noteworthy new ADEs include drug inefficacy, suicidal ideation, restless legs syndrome, and somnambulism. Furthermore, a relationship has been observed between modafinil use and restricted fetal growth, spontaneous abortion, cognitive disorders, and drug inefficacy and abuse. Conclusion: The majority of observed adverse reactions in this study were consistent with those listed in the product instructions. However, potential novel or notable ADE signals were identified through real-world pharmacovigilance analysis. It is anticipated that this paper will offer additional information regarding safe and rational medication for narcolepsy. [ABSTRACT FROM AUTHOR]

Sleep affects the functioning of all biological processes in the human body. Sleep disorders disrupt the well‐being of an individual and can potentially lead to other health complications. It affects a large part of the population, and their timely and efficient detection is crucial for improving the quality of health. Sleep disorders are generally analyzed using polysomnogram (PSG) signals, which must be captured in sophisticated laboratory settings. However, electrocardiogram (ECG) signals provide information about the electrical activity of the heart, which is strongly linked with disturbances in sleep and can be used as an indicator of disordered sleep. Along with that, the recording of ECG signals is much easier than other signals and can be done remotely without causing any significant disturbance to the subject. This brings practicality to the systems that are already being employed for sleep disorder detection. In this paper, we present a method for identifying types of sleep disorders using ECG signals. The objective of this paper is to investigate the use of ECG signals for the automated identification of insomnia, narcolepsy, periodic leg movement (PLM), rapid eye movement (REM) behavior disorder (RBD), and nocturnal frontal lobe epilepsy (NFLE) against healthy subjects. We aim to develop a machine learning‐based algorithm that automatically classifies ECG signals into these sleep disorder categories. The cyclic alternating pattern (CAP) sleep database was used in this study, which contains PSG recordings from individuals with and without sleep disorders, including insomnia, narcolepsy, PLM, RBD, and NFLE. A wavelet scattering network has been used to extract features from the ECG signals. Various classifiers were tested, and the ensemble bag of trees classifier provided the optimum performance. An overall accuracy of 98% was obtained for the identification of sleep disorders, along with a classification accuracy of 99.37%, 99.45%, 99.23%, 99.4%, and 99.65% for insomnia, narcolepsy, NFLE, PLM, and RBD, respectively, for binary classification against healthy subject data. Our results show that wavelet scattering network and ensemble of bagged tree (EbagT) classification can accurately identify various sleep disorders. They provided evidence that ECG signals can be used to identify and diagnose sleep disorders, which could lead to the development of accurate detection of these sleep disorders. Also, our study demonstrated the effectiveness of the proposed algorithm in identifying multiple sleep disorders, which could lead to more efficient and cost‐effective diagnosis and treatment of sleep disorders. [ABSTRACT FROM AUTHOR]

The mechanisms underlying the individual need for sleep are unclear. Sleep duration is indeed influenced by multiple factors, such as genetic background, circadian and homeostatic processes, environmental factors, and sometimes transient disturbances such as infections. In some cases, the need for sleep dramatically and chronically increases, inducing a daily-life disability. This "excessive need for sleep" (ENS) was recently proposed and defined in a European Position Paper as a dimension of the hypersomnolence spectrum, "hypersomnia" being the objectified complaint of ENS. The most severe form of ENS has been described in Idiopathic Hypersomnia, a rare neurological disorder, but this disabling symptom can be also found in other hypersomnolence conditions. Because ENS has been defined recently, it remains a symptom poorly investigated and understood. However, protocols of long-term polysomnography recordings have been reported by expert centers in the last decades and open the way to a better understanding of ENS through a neurophysiological approach. In this narrative review, we will 1) present data related to the physiological and pathological variability of sleep duration and their mechanisms, 2) describe the published long-term polysomnography recording protocols, and 3) describe current neurophysiological tools to study sleep microstructure and discuss perspectives for a better understanding of ENS., Competing Interests: Declaration of competing interest The authors report no financial or non-financial conflicts of interest in this work., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: Physical 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/methods: Patients 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., Results: Twenty-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., Conclusions: Most 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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The authors declare no conflict of interestBrunel Lisa reports financial support was provided by French Society for Sleep Research And Sleep Medicine. Franco Patricia reports a relationship with Bioprojet Biotech that includes: speaking and lecture fees and travel reimbursement. Franco Patricia reports a relationship with Biocodex SA that includes: board membership, speaking and lecture fees, and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: It is hypothesized that narcolepsy type 1 (NT1) develops in genetically susceptible people who encounter environmental triggers leading to immune-mediated hypocretin-1 deficiency. The pathophysiologies of narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) remain unknown. The main aim of this study was to collect all reported immunological events before onset of a central disorder of hypersomnolence., Methods: Medical records of 290 people with NT1, and 115 with NT2 or IH were retrospectively reviewed to extract infection and influenza vaccination history. Prevalence, distribution of immunological events, and time until hypersomnolence onset were compared between NT1 and the combined group of NT2 and IH., Results: Immunological events were frequently reported before hypersomnolence disorder onset across groups. Flu and H1N1 influenza vaccination were more common in NT1, and Epstein-Barr virus and other respiratory and non-respiratory infections in NT2 and IH. Distributions of events were comparable between NT2 and IH. Rapid symptom onset within one month of infection was frequent across groups, especially after flu infection in NT1. Hypersomnolence disorder progression after an immunological event was reported in ten individuals., Conclusions: Our findings suggest a variety of immunological triggers potentially related to NT1, including H1N1 influenza infection or vaccination, infection with other flu types, and other respiratory and non-respiratory infections. Frequent reports of immunological events (other than those reported in NT1) immediately prior to the development of NT2 and IH support the specificity of triggers for NT1, and open important new research avenues into possible underlying immunological mechanisms in NT2 and IH., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lammers GJ reports a relationship with Alkermes plc that includes: consulting or advisory. Lammers GJ reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory. Lammers GJ reports a relationship with Bioprojet that includes: consulting or advisory. Lammers GJ reports a relationship with Jazz Pharmaceuticals plc that includes: consulting or advisory. Fronczek R reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory. Fronczek R reports a relationship with Bioprojet that includes: consulting or advisory, funding grants, and speaking and lecture fees. Fronczek R reports a relationship with Jazz Pharmaceuticals plc that includes: funding grants. Khatami R reports a relationship with Neuraxpharm that includes: consulting or advisory. Khatami R reports a relationship with Idorsia Pharmaceuticals Ltd that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The gold standard investigation for central disorders of hypersomnolence is the Multiple Sleep Latency Test (MSLT). As the clinical features of these disorders of hypersomnolence evolve with time in children, clinicians may consider repeating a previously non-diagnostic MSLT. Currently there are no guidelines available regards the utility and timing of repeating paediatric MSLTs., Methods: Retrospective review of children aged 3-18years with ≥2MSLTs between 2005 and 2022. Narcolepsy was defined as mean sleep latency (MSL) <8min with ≥2 sleep onset REM (SOREM); idiopathic hypersomnia (IH) was defined as MSL <8min with <2 SOREM. MSLTs not meeting these criteria were labelled non-diagnostic., Results: 19 children (9 female) with initial non-diagnostic MSLT underwent repeat MSLT, with 6 proceeding to a 3rd MSLT following 2 non-diagnostic MSLTs. The 2nd MSLT resulted in diagnosis in 6/19 (32 %) (3 narcolepsy, 3 IH); and 2/6 (33 %) 3rd MSLT were diagnostic (2 IH). Median age at initial MSLT was 7.5y (range 3.4-17.8y), with repeat performed after median of 2.9y (range 0.9-8.2y), and 3rd after a further 1.9 years (range 1.2-4.2y). Mean change in MSL on repeat testing was -2min (range -15.5min to +4.9min, p = 0.18). Of the 8 diagnostic repeat MSLTs, in addition to the MSL falling below 8 min, 2 children also developed ≥2 SOREM that had not been previously present., Conclusions: A third of repeat MSLTs became diagnostic, suggesting repeat MSLT should be considered in childhood if clinical suspicion persists. Further work needs to address the ideal interval between MSLTs and diagnostic cut-points specific to the paediatric population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Excessive daytime sleepiness (EDS) is common in childhood and is currently quantified using adult criteria on a multiple sleep latency test (MSLT). This study aimed to describe paediatric MSLT results, particularly focussing on a previously proposed alternative mean sleep latency (MSL) threshold for children of 12 min, and assess the impact of a 5th nap. We performed a retrospective analysis of MSLTs at a single paediatric centre from 2004 to 2021. Narcolepsy was defined as a mean sleep latency (MSL) ≤8min with ≥2 sleep onset REM (SOREM) periods. Idiopathic Hypersomnia (IH) was defined as a MSL ≤8min with <2 SOREMs. An ambiguous MSLT result was defined as a MSL 8-12min and/or ≥2 SOREM periods. Of 214 MSLTs [50 % female, median age 14.0y (range 3.3-20.1y)], narcolepsy was diagnosed in 48 (22 %), IH in 22 (10 %) and the result was ambiguous in 44 (21 %). Those with ambiguous MSLT results were older (15.6 vs 13.4y, p = 0.006) with a higher proportion of females (61 % vs 35 %, p = 0.01) in comparison to the narcolepsy group. A 5th nap was performed in 60 (28 %) of MSLTs and only changed the outcome in one case. In conclusion, MSLT results are borderline in 21 % of paediatric cases, suggesting that current adult diagnostic criteria may miss narcolepsy and IH in children. A 5th nap usually makes no difference or increases the MSL, suggesting that a four nap MSLT protocol could be used apart from rare cases where the result is borderline after the 4th nap., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Fatigue is a frequent complaint among patients with narcolepsy. Studies have shown that inflammatory cytokines are associated with fatigue in neurological disorders; however, this association has not been identified in patients with type 1 narcolepsy. The purpose of this study was to investigate the potential relationship between cytokines and fatigue in patients with type 1 narcolepsy., Methods: We investigated the association between 12 inflammatory cytokines and fatigue in 49 patients with type 1 narcolepsy. The Multidimensional Fatigue Inventory-20 was used to assess the fatigue severity. The associations of fatigue were identified using Spearman and Pearson correlation analyses. A linear regression analysis model was used to adjust the confounding factors and evaluate the associations of fatigue., Results: Correlation analysis showed that the plasma interleukin (IL)-2 level (r = 0.409, p = 0.004) was positively correlated with fatigue in patients with narcolepsy type 1. After adjusting for confounding factors, the linear regression model revealed a positive association between the IL-2 level (β = 1.148, p = 0.04) and fatigue in individuals diagnosed with type 1 narcolepsy., Conclusion: IL-2 levels show a positive correlation with fatigue in type 1 narcolepsy, suggesting its potential role in the pathophysiology of fatigue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: - Narcolepsy type 1 (NT1) is a rare chronic sleep disorder, usually arising by adolescence that negatively impacts quality of life. It is characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic/hypnopompic hallucinations, sleep paralysis and sleep fragmentation. The goals of this work were to characterize NT1 adolescents regarding sleep characteristics, health-related quality of life (HRQoL) and future life perspectives and later to compare this group with a control group of healthy adolescents (HA)., Methods: - Transversal descriptive/analytical study including NT1 patients followed in a sleep center of a tertiary hospital and 23 HA. Data were collected through an online survey, fulfilled by the participants, including four sections: demographics; questionnaire evaluating sleep and EDS; questionnaire evaluating HRQoL; inquiry regarding future perspectives. An extra section for the NT1 group only, comprising questions about the characterization of narcolepsy, was included., Results: 22 NT1 adolescents were included, with a median age of 15.0 years-old. Beyond EDS, all had presented cataplexy - 19 still reported it. Twenty patients took psychostimulants regularly for EDS, while 13 patients took venlafaxine or fluoxetine for cataplexy. Nineteen adolescents took regular naps and 19 maintained psychological appointments. Self-reported sleep quality was similar between groups (p = 0.112). EDS was identified in seven NT1 patients and none in the control group. HRQOL was significantly lower in NT1 patients only for the physical well-being domain (p = 0.001). Regarding future perspectives, results were similar, except for a lower probability of getting a driver's license in NT1 patients, despite no statistical significance (p = 0.104)., Discussion: Daytime sleepiness is difficult to control in NT1, despite specialized treatment. HRQoL was similar between groups in all domains except for the physical well-being. Despite good adherence to pharmacological and non-pharmacological treatments (namely psychological therapy) that account for these good results, the physical well-being domain is difficult to manage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rationale and Objectives: To explore indicators of neuropsychological changes in patients with type 1 narcolepsy (NT1) using resting-state functional magnetic resonance imaging (rs-fMRI)., Materials and Methods: Thirty-four NT1 patients and 34 age- and sex-matched healthy volunteers were recruited for neuropsychiatric assessments and rs-fMRI data acquisition. Fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and related brain functional connectivity (FC) were calculated for the two groups and compared using a two-sample t test with cluster-level FDR correction. Moreover, partial correlation analysis was performed between these functional values of changed brain regions and clinical scales., Results: Compared to those of healthy controls, spontaneous functional activities were significantly weakened in patients with NT1 in regions such as the left/right posterior cerebellum lobe, left inferior temporal gyrus, and left dorsolateral superior frontal gyrus, whereas those in regions such as the left middle occipital gyrus, right inferior occipital gyrus, and left/right lingual gyrus were significantly strengthened. Furthermore, NT1 patients displayed significantly changed FCs between the left/right anterior cingulate gyrus (ACG) and regions such as the left/right cerebellum, left middle occipital gyrus, and left inferior frontal gyrus in the operculum. In partial correlation analysis, the functions in the left dorsolateral superior frontal gyrus were significantly related to the Trail Making Tests (TMT) score. Moreover, the FC between the left ACG and left inferior frontal gyrus in the operculum was highly correlated with anxiety and depression features, including the Hamilton Anxiety Scale (HAMA) score and Hamilton Depression Rating Scale (HAMD-17) score., Conclusion: Patients with NT1 exhibited abnormalities in the anterior cingulate cortex, frontal-parietal cortex, hippocampus, and left/right posterior cerebellum lobe. The deactivation of the left frontal-temporal cortex is stronger, which is involved in the cognitive decline and mental disorders in these patients. Damage to the ACG may affect its FC with other regions and cause cognition and emotion dysregulation, perhaps by impairing patients' visual pathways and frontal-temporal-parietal networks. Hence, these could be important biomarkers for their neuropsychological changes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: To explore topological alterations of white matter (WM) structural connectome, and their associations with clinical characteristics in type 1 narcolepsy (NT1)., Methods: 46 NT1 patients and 34 age- and sex-matched healthy controls were recruited for clinical data and diffusion tensor imaging collection. Using graph theory analysis, the topology metrics of structural connectome, rich club organization, and connectivity properties were compared between two groups. Furthermore, partial correlation analysis was performed between the network characteristics of 90 nodes or weakened edges and clinical data using Pearson or Spearman correlation, controlling by age and sex., Results: Between-group comparison reflected that NT1 patients exhibited sleep disorders with comorbidities of impaired cognition and psychological problems. In patients, the global efficiency, local efficiency, and average clustering coefficient were significantly lower, whereas characteristic path length was larger compared to healthy control. Pertinently, nodal path length of left middle frontal gyrus was positively correlated with Pittsburgh Sleep Quality Index scores. The rich club analysis identified six affected nodes: bilateral dorsolateral superior frontal gyrus, bilateral supplementary motor area, left hippocampus, and left pallidum. Furthermore, six significantly weakened structural connections seeding from these rich club nodes have shown significant correlations with clinical index or polysomnography parameters., Conclusion: In NT1 patients, WM structural connectome has shown to be disrupted, which were primarily distributed in frontal-parietal cortex, subcortical regions, and particularly cingulate, potentially affecting their clinical manifestations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objective: People with epilepsy frequently encounter sleep disruptions that can stem from a variety of complex factors. Epilepsy-related sleep disturbance can lead to reduced quality of life and excessive daytime hypersomnolence. Identification of sleep disturbances may help in the overall management of epilepsy patients. This study was conducted to determine the prevalence and predictors of poor sleep quality and daytime sleepiness in epilepsy., Methods: A cross-sectional study on 284 epilepsy patients was performed in a local tertiary centre. The demographic and clinical epilepsy data were collected. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires were utilised to determine the quality of life and daytime hypersomnolence of epilepsy patients, respectively., Results: Poor sleep quality was reported in 78 (27.5%) patients while daytime hypersomnolence was present in 17 (6%) patients. The predictors of poor sleep quality include structural causes (OR = 2.749; 95% CI: 1.436, 5.264, p = 0.002), generalised seizures (OR = 1.959, 95% CI: 1.04, 3.689, p = 0.037), and antiseizure medications such as Carbamazepine (OR = 2.34; 95% CI: 1.095, 5.001, p = 0.028) and Topiramate (OR 2.487; 95% CI: 1.028, 6.014, p = 0.043). Females are 3.797 times more likely score higher in ESS assessment (OR 3.797; 95% CI: 1.064, 13.555 p = 0.04)., Discussion: Sleep disturbances frequently coexist with epilepsy. Patients should be actively evaluated using the PSQI and ESS questionnaires. It is imperative to identify the key factors that lead to reduced sleep quality and heightened daytime sleepiness in patients with epilepsy, as this is essential to properly manage their condition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Daytime sleepiness is common amongst children and adolescents. Inadequate sleep duration, inappropriate school start times, and the delay in sleep phase of adolescence may all contribute. Nocturnal sleep disruption due to sleep disorders such as obstructive sleep apnea or restless legs syndrome/periodic limb movement disorder may also lead to daytime sleepiness. Profound sleepiness however, when occurring in the setting of adequate sleep duration, is rare amongst children and adolescents and may prompt consideration of a central disorder of hypersomnolence (CDH). Narcolepsy is the archetypal and most studied form of CDH and a detailed review of the presentation, evaluation, treatment of narcolepsy is included separately in this edition of Seminars in Pediatric Neurology. In addition to narcolepsy, 2 other forms of primary CDH exist, idiopathic hypersomnia (IH) and Kleine-Levin syndrome (KLS). Onset of IH and KLS occurs most frequently during the pediatric age range and presentation may include signs of encephalopathy in addition to hypersomnolence. As such, they are of particular relevance to pediatric neurology and associated fields. Unfortunately, when compared to narcolepsy little is known about IH and KLS, at both the physiologic and clinical level. This review will focus on the presentation, evaluation, and management of idiopathic hypersomnia and Kleine-Levin syndrome in the pediatric population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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

Narcolepsy type 1 (NT1) and type 2 (NT2), also known as narcolepsy with and without cataplexy, are sleep disorders that benefited from major scientific advances over the last two decades. NT1 is caused by the loss of hypothalamic neurons producing orexin/hypocretin, a neurotransmitter regulating sleep and wake, which can be measured in the cerebrospinal fluid (CSF). A low CSF level of hypocretin-1/orexin-A is a highly specific and sensitive biomarker, sufficient to diagnose NT1. Orexin-deficiency is responsible for the main NT1 symptoms: sleepiness, cataplexy, disrupted nocturnal sleep, sleep-related hallucinations, and sleep paralysis. In the absence of a lumbar puncture, the diagnosis is based on neurophysiological tests (nocturnal and diurnal) and the presence of the pathognomonic symptom cataplexy. In the revised version of the International Classification of sleep Disorders, 3rd edition (ICSD-3-TR), a sleep onset rapid eye movement sleep (REM) period (SOREMP) (i.e. rapid occurrence of REM sleep) during the previous polysomnography may replace the diurnal multiple sleep latency test, when clear-cut cataplexy is present. A nocturnal SOREMP is very specific but not sensitive enough, and the diagnosis of cataplexy is usually based on clinical interview. It is thus of crucial importance to define typical versus atypical cataplectic attacks, and a list of clinical features and related degrees of certainty is proposed in this paper (expert opinion). The time frame of at least three months of evolution of sleepiness to diagnose NT1 was removed in the ICSD-3-TR, when clear-cut cataplexy or orexin-deficiency are established. However, it was kept for NT2 diagnosis, a less well-characterized disorder with unknown clinical course and absence of biolo biomarkers; sleep deprivation, shift working and substances intake being major differential diagnoses. Treatment of narcolepsy is nowadays only symptomatic, but the upcoming arrival of non-peptide orexin receptor-2 agonists should be a revolution in the management of these rare sleep diseases., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background and aims: Orphan diseases, or rare diseases, are defined in Europe as diseases that affect less than 5 out of every 10,000 citizens. Given the small number of cases and the lack of profit potential, pharmaceutical companies have not invested much in the development of possible treatments. However, over the last few years, new therapies for rare diseases have emerged, giving physicians a chance to offer personalized treatment. With this paper, we aim to present some of the orphan neurological diseases for which new drugs have been developed lately. Methods: We have conducted a literature review of the papers concerning rare diseases and their treatment, and we have analyzed the existing studies for each orphan drug. For this purpose, we have used the Google Scholar search engine and the Orphanet. We have selected the studies published in the last 15 years. Results. Since the formation of the National Organization for Rare Diseases, the Orphan Drug Act, and the National Institutes of Health Office of Rare Diseases, pharmacological companies have made a lot of progress concerning the development of new drugs. Therefore, diseases that until recently were without therapeutic solutions benefit today from personalized treatment. We have detailed in our study over 15 neurological and systemic diseases with neurological implications, for which the last 10–15 years have brought important innovations regarding their treatment. Conclusions: Many steps have been taken towards the treatment of these patients, and the humanity and professionalism of the pharmaceutical companies, along with the constant support of the patient's associations for rare diseases, have led to the discovery of new treatments and useful future findings. [ABSTRACT FROM AUTHOR]

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