OBJECTIVE AND BACKGROUND: Health-related quality of life (HRQoL) is reduced in narcolepsy type 1 (NT1), but proper information on HRQoL in narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) is lacking. This study examines HRQoL of NT1, NT2, IH, and healthy controls (HC) and assesses the HRQoL associates in these diseases. PATIENTS AND METHODS: 117 adults (64 NT1, 22 NT2, 31 IH; 61.5 % women; 38.3 ± 12.0 years; 71.8 % treated) and 41 HC (53.7 % women; 35.9 ± 9.6 years) completed questionnaires assessing sleepiness, fatigue, symptoms severity, sleep inertia, depressive and anxiety symptoms, HRQoL, and underwent a semi-structured interview. Data were analyzed using the Mann-Whitney and Kruskal-Wallis tests, Spearman's correlation coefficient, and regression analysis. RESULTS: HRQoL of NT1, NT2, and IH, separately, was poorer compared to HC (p < 0.001). According to the 36-Item Short Form Health Survey, the mental HRQoL was more impaired in NT2 and IH than NT1 (p < 0.05) in association with more pronounced depressive symptoms (p < 0.01; p < 0.05, respectively) and sleep inertia (p < 0.01; p < 0.01, respectively). Psychiatric disorders were more prevalent in NT2 and IH versus NT1 (p < 0.05). CONCLUSION: HRQoL is reduced in NT1, NT2, and IH, with this reduction being more pronounced in NT2 and IH. Poor mental HRQoL of NT2 and IH was associated both with the severity of depressive symptoms and more intense sleep inertia.

• MeSH
• deprese psychologie   MeSH
• dospělí MeSH
• idiopatická hypersomnie * psychologie   MeSH
• kvalita života * psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• narkolepsie * psychologie   MeSH
• průzkumy a dotazníky MeSH
• stupeň závažnosti nemoci MeSH
• únava psychologie   MeSH
• úzkost psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• narkolepsie * farmakoterapie   MeSH
• stimulanty centrálního nervového systému terapeutické užití   farmakologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• stimulanty centrálního nervového systému MeSH

Little attention has been paid to the long-term development of idiopathic hypersomnia symptoms and idiopathic hypersomnia comorbidities. The aim of this study was to describe the general health of patients with idiopathic hypersomnia years after the initial diagnosis, focusing on current subjective hypersomnolence and the presence of its other possible causes. Adult patients diagnosed with idiopathic hypersomnia ≥ 3 years ago at sleep centres in Prague and Kosice were invited to participate in this study. A total of 60 patients were examined (age 47.3 ± SD = 13.2 years, 66.7% women). In all participants, their hypersomnolence could not be explained by any other cause but idiopathic hypersomnia at the time of diagnosis. The mean duration of follow-up was 9.8 + 8.0 years. Fifty patients (83%) reported persisting hypersomnolence, but only 33 (55%) had no other disease that could also explain the patient's excessive daytime sleepiness and/or prolonged sleep. In two patients (3%), the diagnosis in the meantime had changed to narcolepsy type 2, and 15 patients (25%) had developed a disease or diseases potentially causing hypersomnolence since the initial diagnosis. Complete hypersomnolence resolution without stimulant treatment lasting longer than 6 months was reported by 10 patients (17%). To conclude, in a longer interval from the diagnosis of idiopathic hypersomnia, hypersomnolence may disappear or may theoretically be explained by another newly developed disease, or the diagnosis may be changed to narcolepsy type 2. Thus, after 9.8 years, only 55% of the examined patients with idiopathic hypersomnia had a typical clinical picture of idiopathic hypersomnia without doubts about the cause of the current hypersomnolence.

• Klíčová slova
• comorbidity, depression, diagnosing, follow-up, hypersomnolence, idiopathic hypersomnia,
• MeSH
• dospělí MeSH
• idiopatická hypersomnie * diagnóza   epidemiologie   farmakoterapie   MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• narkolepsie * diagnóza   epidemiologie   MeSH
• poruchy nadměrné spavosti * diagnóza   epidemiologie   komplikace   MeSH
• pozornost MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

STUDY OBJECTIVES: Microbial antigens can elicit an immune response leading to the production of autoantibodies cross-reacting with autoantigens. Still, their clinical significance in human sera in the context of brain diseases is unclear. Therefore, assessment of natural autoantibodies reacting with their neuropeptides may elucidate the autoimmune etiology of central hypersomnias. The study aims to determine whether serum autoantibody levels differ in patients with different types of central hypersomnias (narcolepsy type 1 and 2, NT1 and NT2; idiopathic hypersomnia, IH) and healthy controls and if the differences could suggest the participation of autoantibodies in disease pathogenesis. METHODS: Sera from 91 patients with NT1, 27 with NT2, 46 with IH, and 50 healthy controls were examined for autoantibodies against assorted neuropeptides. Participants were screened using questionnaires related to sleep disorders, quality of life, and mental health conditions. In addition, serum biochemical parameters and biomarkers of microbial penetration through the intestinal wall were determined. RESULTS: A higher prevalence of autoantibodies against neuropeptides was observed only for alpha-melanocytes-stimulating hormone (α-MSH) and neuropeptide glutamic acid-isoleucine (NEI), which differed slightly among diagnoses. Patients with both types of narcolepsy exhibited signs of microbial translocation through the gut barrier. According to the questionnaires, patients diagnosed with NT2 or IH had subjectively worse life quality than patients with NT1. Patients displayed significantly lower levels of bilirubin and creatinine and slightly higher alkaline phosphatase values than healthy controls. CONCLUSIONS: Overall, serum anti-neuronal antibodies prevalence is rare, suggesting that their participation in the pathophysiology of concerned sleep disorders is insignificant. Moreover, their levels vary slightly between diagnoses indicating no major diagnostic significance.

• Klíčová slova
• Autoantibodies, Hypersomnia, Immunity, Narcolepsy, Neuropeptides, Sleepiness,
• MeSH
• autoprotilátky MeSH
• kvalita života MeSH
• lidé MeSH
• narkolepsie * epidemiologie   MeSH
• neuropeptidy * MeSH
• poruchy nadměrné spavosti * epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• autoprotilátky MeSH
• neuropeptidy * MeSH

In recent years, there has been an increased interest in elucidating the influence of the gut microbiota on sleep physiology. The gut microbiota affects the central nervous system by modulating neuronal pathways through the neuroendocrine and immune system, the hypothalamus-pituitary-adrenal axis, and various metabolic pathways. The gut microbiota can also influence circadian rhythms. In this study, we observed the gut microbiota composition of patients suffering from narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. We did not observe any changes in the alpha diversity of the gut microbiota among patient groups and healthy controls. We observed changes in beta diversity in accordance with Jaccard dissimilarities between the control group and groups of patients suffering from narcolepsy type 1 and idiopathic hypersomnia. Our results indicate that both these patient groups differ from controls relative to the presence of rare bacterial taxa. However, after adjustment for various confounding factors such as BMI, age, and gender, there were no statistical differences among the groups. This indicates that the divergence in beta diversity in the narcolepsy type 1 and idiopathic hypersomnia groups did not arise due to sleep disturbances. This study implies that using metabolomics and proteomics approaches to study the role of microbiota in sleep disorders might prove beneficial.

• Klíčová slova
• Central disorders of hypersomnolence, Gut microbiota, Idiopathic hypersomnia, Microbiota-gut-brain axis, Narcolepsy type 1, Narcolepsy type 2, Sleep,
• MeSH
• idiopatická hypersomnie * MeSH
• lidé MeSH
• narkolepsie * MeSH
• poruchy nadměrné spavosti * MeSH
• poruchy spánku a bdění * MeSH
• spánek MeSH
• střevní mikroflóra * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

• MeSH
• autoimunita genetika   MeSH
• autoimunitní nemoci * epidemiologie   genetika   MeSH
• chřipka lidská * epidemiologie   genetika   MeSH
• lidé MeSH
• narkolepsie * chemicky indukované   genetika   MeSH
• vakcíny proti chřipce * škodlivé účinky   MeSH
• virus chřipky A, podtyp H1N1 * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• vakcíny proti chřipce * MeSH

BACKGROUND AND OBJECTIVES: Recent studies fueled doubts as to whether all currently defined central disorders of hypersomnolence are stable entities, especially narcolepsy type 2 and idiopathic hypersomnia. New reliable biomarkers are needed, and the question arises of whether current diagnostic criteria of hypersomnolence disorders should be reassessed. The main aim of this data-driven observational study was to see whether data-driven algorithms would segregate narcolepsy type 1 and identify more reliable subgrouping of individuals without cataplexy with new clinical biomarkers. METHODS: We used agglomerative hierarchical clustering, an unsupervised machine learning algorithm, to identify distinct hypersomnolence clusters in the large-scale European Narcolepsy Network database. We included 97 variables, covering all aspects of central hypersomnolence disorders such as symptoms, demographics, objective and subjective sleep measures, and laboratory biomarkers. We specifically focused on subgrouping of patients without cataplexy. The number of clusters was chosen to be the minimal number for which patients without cataplexy were put in distinct groups. RESULTS: We included 1,078 unmedicated adolescents and adults. Seven clusters were identified, of which 4 clusters included predominantly individuals with cataplexy. The 2 most distinct clusters consisted of 158 and 157 patients, were dominated by those without cataplexy, and among other variables, significantly differed in presence of sleep drunkenness, subjective difficulty awakening, and weekend-week sleep length difference. Patients formally diagnosed as having narcolepsy type 2 and idiopathic hypersomnia were evenly mixed in these 2 clusters. DISCUSSION: Using a data-driven approach in the largest study on central disorders of hypersomnolence to date, our study identified distinct patient subgroups within the central disorders of hypersomnolence population. Our results contest inclusion of sleep-onset REM periods in diagnostic criteria for people without cataplexy and provide promising new variables for reliable diagnostic categories that better resemble different patient phenotypes. Cluster-guided classification will result in a more solid hypersomnolence classification system that is less vulnerable to instability of single features.

• MeSH
• idiopatická hypersomnie * diagnóza   MeSH
• kataplexie * diagnóza   MeSH
• lidé MeSH
• mladiství MeSH
• narkolepsie * diagnóza   farmakoterapie   MeSH
• poruchy nadměrné spavosti * diagnóza   epidemiologie   MeSH
• shluková analýza MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

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.

People with narcolepsy are often sleepy during the day. They may also have sudden muscle weakness (known as cataplexy). Lower-sodium oxybate (LXB) is a narcolepsy medicine that is similar to sodium oxybate (SXB) but has 92% less sodium. A recent study found that treatment with LXB was better at reducing how often people with narcolepsy had sleepiness and cataplexy than no medicine at all (NCT03030599). This paper is about the first 12 weeks of that study, when all the people taking part in the study first tried LXB to check that they were being given the right amount. In people who only took LXB, cataplexy happened less often over time. Some people were already taking other medicines to treat their cataplexy (such as antidepressants), so they were asked to slowly stop those medicines while taking LXB. In those people, cataplexy happened more often at first as they stopped taking antidepressants and then less often later on. The increase in cataplexy when antidepressants were stopped was smaller in people who switched from SXB to LXB. This study shows that many people getting treatment for narcolepsy can switch to LXB without their cataplexy becoming worse.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• kataplexie * farmakoterapie   MeSH
• lidé MeSH
• narkolepsie * chemicky indukované   farmakoterapie   MeSH
• oxybát sodný * škodlivé účinky   MeSH
• poruchy nadměrné spavosti * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• oxybát sodný * MeSH

STUDY OBJECTIVES: In some patients, it is difficult to correctly nosologically classify daytime sleepiness. Clinical manifestations may be nonspecific; on the basis of objective measures it is possible to determine the current severity of sleepiness, but they do not always allow accurate diagnosis. It is especially difficult to distinguish between idiopathic hypersomnia (IH) and hypersomnia associated with a psychiatric disorder (PSY). METHODS: To find significant differences between the IH and PSY groups, we included 67 patients (IH, n = 15; PSY, n = 52) in the study, focusing on differences in self-reported symptoms, evaluating current depressive symptoms using the Beck Depression Inventory-II score and personality traits measured by the Temperament and Character Inventory. All of the patients underwent polysomnography, the Multiple Sleep Latency Test, and ad libitum sleep monitoring. RESULTS: The patients with IH showed greater difficulty than those in the PSY group with waking up in the morning (P < .001) and complained of memory (P = .04) and attention deficit (P = .006). They also showed higher total sleep time (P < .001) and sleep efficiency (P = .007) and a shorter mean sleep latency on the Multiple Sleep Latency Test (P < .001). Nevertheless, the IH and PSY groups did not differ in Beck Depression Inventory scores or personality characteristics. CONCLUSIONS: IH is a syndrome in which depression/external life stressors and personality characteristics also play a role. Patients with IH may benefit from the cooperation of sleep specialists with psychotherapists/psychiatrists. CITATION: Bušková J, Novák T, Miletínová E, et al. Self-reported symptoms and objective measures in idiopathic hypersomnia and hypersomnia associated with psychiatric disorders: a prospective cross-sectional study. J Clin Sleep Med. 2022;18(3):713-720.

• Klíčová slova
• depressivity *, hypersomnia associated with psychiatric disorder *, idiopathic hypersomnia *, personality traits *,
• MeSH
• duševní poruchy * komplikace   MeSH
• idiopatická hypersomnie * komplikace   diagnóza   psychologie   MeSH
• lidé MeSH
• narkolepsie * komplikace   MeSH
• poruchy nadměrné spavosti * komplikace   diagnóza   MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• zpráva o sobě MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND AND PURPOSE: Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children. METHODS: The European Academy of Neurology (EAN), European Sleep Research Society (ESRS), and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach. RESULTS: A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness (EDS) in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong); methylphenidate, amphetamine derivatives (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) EDS in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivatives (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions. CONCLUSION: The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.

• Klíčová slova
• European, cataplexy, guideline, management, narcolepsy,
• MeSH
• dítě MeSH
• dospělí MeSH
• kataplexie * MeSH
• lidé MeSH
• modafinil terapeutické užití   MeSH
• narkolepsie * diagnóza   farmakoterapie   MeSH
• oxybát sodný * terapeutické užití   MeSH
• spánek MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• modafinil MeSH
• oxybát sodný * MeSH