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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.)

Objective: /Background: The change in cerebral hemodynamics induced by sleep apneas and hypopneas may contribute to the daytime sleepiness in patients with obstructive sleep apnea (OSA). However, previous studies failed to discovery their relationship. We propose and test a new parameter, the cumulative brain oxygen desaturation, which may contribute to OSA patient's daytime sleepiness., Patients/methods: 22 patients with severe OSA (apnea-hypopnea index (AHI) at diagnosis [mean ± standard deviation, std.]: 52.1 ± 21.6/h, median: 45.1/h, interquartile range: 34.4-60.2/h) were monitored by polysomnography during routine continuous positive airway pressure titration. The reductions of brain tissue oxygen saturation (StO2) in all respiratory events at baseline sleep were measured by frequency-domain near-infrared spectroscopy (NIRS). The cumulative brain desaturation was calculated as AHI times the mean StO2 desaturation (i.e., AHI×ΔStO2‾). Similarly, cumulative peripheral desaturation was also calculated, i.e., AHI×ΔSpO2‾ where ΔSpO2‾ was the mean reduction of peripheral arterial oxygen saturation (SpO2). The correlations between Epworth sleepiness scale (ESS) and AHI, ΔStO2‾, AHI×ΔStO2‾, and AHI×ΔSpO2‾ were tested, respectively. Linear regression was applied to predict ESS using AHI×ΔStO2‾ and AHI×ΔSpO2‾, with age and BMI as covariates., Results: ESS significantly correlates to the cumulative brain desaturation (Pearson's correlation coefficient: 0.68, p = 0.00056), not the other parameters. Regression analysis only finds significant association between ESS and the cumulative cerebral desaturation (p = 0.00195) but not the cumulative peripheral desaturation (p = 0.71)., Conclusions: The cumulative brain oxygen desaturation, which comprehensively combines total sleep time, the frequency of apnea and hypopnea events, and the severity of cerebral oxygen desaturation, is a new indicator for daytime sleepiness in severe OSA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhongxing Zhang and Ramin Khatami report financial support was provided by Clinic Barmelweid Scientific Foundation and Research Fund of the Swiss Lung Association, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives/background: Narcolepsy type 1 (NT1) is an immune-mediated disorder characterized by excessive daytime sleepiness, cataplexy, low levels of hypocretin-1 in the cerebrospinal fluid, and a strong association with the HLA DQB1*06:02 allele. There is evidence for streptococcal infections as one pathogenic factor that may lead to NT1 as part of a multifactorial pathogenesis. Elevated titers of Antistreptolysin-O antibodies and increased inflammatory activity in response to streptococci antigens have been described in patients with NT1. Sydenham chorea (SC) results from a post-streptococcal autoimmune process targeting basal ganglia neurons. Despite this common trigger, SC has been interpreted as a misdiagnosis in a few described cases of patients who were first diagnosed with SC and later with NT1. Our goal was to analyze the association between SC and NT1., Patients/methods: We reviewed the literature and report three patients from three European sleep centers who were diagnosed with both SC and NT1 within a few months., Results: We describe the cases of one male (age 10) and two female (age 22 and 10) patients., Conclusions: We argue that in those cases both diagnoses are justified, unlike reports of previous cases in which SC was considered a misdiagnosis in patients with NT1. It remains, however, unclear if the conditions occur independently or if there is an overlap disorder- an SC-like subtype of narcolepsy with a particular sequence of symptoms. Further studies need to clarify the causality of the relationship and the pathophysiology of the reported rare association., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elena S. Wenz reports a relationship with University of Bern that includes: funding grants. Ulf Kallweit reports a relationship with Bioprojet, Jazz Pharmaceuticals, Takeda Pharmaceuticals that includes: consulting or advisory and speaking and lecture fees. Rolf Fronczek reports a relationship with Takeda Pharmaceuticals, Bioprojet that includes: consulting or advisory. Rolf Fronczek reports a relationship with Jazz Pharmaceuticals that includes: funding grants. Gert Jan Lammers reports a relationship with Bioprojet, Jazz Pharmaceuticals, Takeda Pharmaceuticals, NLS Pharmaceutics that includes: consulting or advisory and speaking and lecture fees., (Copyright © 2023. Published by Elsevier B.V.)

Narcolepsy with cataplexy (NT1) is a chronic hypothalamic disorder with a presumed immune-mediated etiology leading to a loss of hypocretin neurons. Previous studies reported conflicting results in terms of presence of auto-antibodies involved in narcolepsy pathophysiology. A total of 86 patients with primary/idiopathic narcolepsy (74 NT1, 12 NT2) and 23 control patients with excessive daytime sleepiness due to other causes were tested for the presence of a wide range of anti-neuronal antibodies in both serum and cerebrospinal fluid (CSF). Anti-neuronal antibodies were rarely found in patients with narcolepsy (n = 2) and in controls (n = 1). Our results are in line with previous reports. We can therefore support the current evidence, that conventional anti-neuronal antibodies are not routinely detected during the workup of NT1 and other CDH patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Short mean latencies to the first epoch of non-rapid eye movement sleep stage 1 (NREM1) and the presence of >or= 2 sleep onset REM (SOREM) periods on multiple sleep latency test (MSLT) occur in both narcolepsy-cataplexy (NC) and behaviourally induced insufficient sleep syndrome (BIISS). It is not known whether specific MSLT findings help differentiate the two disorders., Methods: We analyzed MSLT data including sleep latencies to and between different sleep stages of 60 age-, gender- and body mass index (BMI)-matched subjects (hypocretin-deficient NC, actigraphy-confirmed BIISS, healthy controls: each 20)., Results: Mean latency (in minutes) to NREM1 sleep was significantly shorter in NC (1.8+/-1.5) than in BIISS (4.7+/-2.1, p<0.001) and controls (11.4+/-3.3, p<0.001). Mean latency to NREM2 sleep was similar in NC (8.6+/-4.7) and BIISS (8.1+/-2.7, p=0.64); latency to either NREM2 or rapid eye movement (REM) sleep (i.e., the sum of the sleep latency to NREM1 and the duration of the first NREM1 sleep sequence), however, was shorter in NC (4.4+/-2.9) than in BIISS (7.9+/-3.5, p<0.001). Referring to all naps with SOREM periods, the sequence NREM1-REM-NREM2 was more common (71%) in NC than in BIISS (15%, p<0.001), reflecting the shorter latency from NREM1 to NREM2 in BIISS (3.7+/-2.5) than in NC (6.1+/-5.9, p<0.001)., Conclusions: Our findings show that both sleepiness (as measured by NREM1 sleep latency) and REM sleep propensity are higher in NC than in BIISS. Furthermore, our finding of frequent REM sleep prior to NREM2 sleep in NC is in line with the recent assumption of an insufficient NREM sleep intensity in NC. Together with detailed clinical interviews, sleep logs, actigraphy, and nocturnal polysomnography, mean sleep latencies to NREM1