The aim of the present study was to examine gender and age-specific effects on subjective daytime sleepiness (as measured by the Epworth Sleepiness Scale), body weight and eating behaviour in patients with central disorders of hypersomnolence. Based on the European Narcolepsy Network database, we compared 1035 patients with narcolepsy type I and 505 patients with other central disorders of hypersomnolence ("narcoleptic borderland"), including narcolepsy type II (N = 308) and idiopathic hypersomnia (N = 174), using logistic regression and general linear models. In the entire study population, the Epworth Sleepiness Scale was higher in women (N = 735, mean age = 30 years, mean Epworth Sleepiness Scale = 16.6 ± SD 3.9) than in men (N = 805, mean age = 32 years, mean Epworth Sleepiness Scale = 15.8 ± SD 4.4). In women with narcolepsy type I (N = 475), both Epworth Sleepiness Scale and body mass index increased in parallel with age. In women of the narcoleptic borderland (N = 260), the Epworth Sleepiness Scale markedly peaked in their early 30s, while body mass index only started to rise at that age. This rise in body mass index following the Epworth Sleepiness Scale peak cannot be explained by sleepiness-induced uncontrolled eating, as self-reported uncontrolled eating was negatively associated with the Epworth Sleepiness Scale in this group. We propose that the narcoleptic borderland harbours a unique cluster of women in their fertile years with an unexplored aetiology requiring further investigation towards tailored interventions.
- MeSH
- Adult MeSH
- Body Mass Index * MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Narcolepsy * physiopathology MeSH
- Disorders of Excessive Somnolence * physiopathology epidemiology MeSH
- Sex Factors MeSH
- Feeding Behavior MeSH
- Body Weight MeSH
- Age Factors MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
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
- Depression psychology MeSH
- Adult MeSH
- Idiopathic Hypersomnia * psychology MeSH
- Quality of Life * psychology MeSH
- Middle Aged MeSH
- Humans MeSH
- Narcolepsy * psychology MeSH
- Surveys and Questionnaires MeSH
- Severity of Illness Index MeSH
- Fatigue psychology MeSH
- Anxiety psychology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Narcolepsy * drug therapy MeSH
- Central Nervous System Stimulants therapeutic use pharmacology MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Publication type
- Letter 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.
- MeSH
- Adult MeSH
- Idiopathic Hypersomnia * diagnosis epidemiology drug therapy MeSH
- Comorbidity MeSH
- Middle Aged MeSH
- Humans MeSH
- Narcolepsy * diagnosis epidemiology MeSH
- Disorders of Excessive Somnolence * diagnosis epidemiology complications MeSH
- Attention MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article 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.
- MeSH
- Autoantibodies MeSH
- Quality of Life MeSH
- Humans MeSH
- Narcolepsy * epidemiology MeSH
- Neuropeptides * MeSH
- Disorders of Excessive Somnolence * epidemiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article 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.
- MeSH
- Idiopathic Hypersomnia * MeSH
- Humans MeSH
- Narcolepsy * MeSH
- Disorders of Excessive Somnolence * MeSH
- Sleep Wake Disorders * MeSH
- Sleep MeSH
- Gastrointestinal Microbiome * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Humans MeSH
- Methylphenidate pharmacology adverse effects therapeutic use MeSH
- Adolescent MeSH
- Narcolepsy * diagnosis drug therapy MeSH
- Polysomnography methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Child MeSH
- Adult MeSH
- Idiopathic Hypersomnia diagnosis drug therapy MeSH
- Cataplexy diagnosis drug therapy MeSH
- Humans MeSH
- Narcolepsy diagnosis drug therapy MeSH
- Polysomnography methods MeSH
- Disorders of Excessive Somnolence * diagnosis etiology classification MeSH
- Sleep Latency physiology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Case Reports 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
- Autoimmunity genetics MeSH
- Autoimmune Diseases * epidemiology genetics MeSH
- Influenza, Human * epidemiology genetics MeSH
- Humans MeSH
- Narcolepsy * chemically induced genetics MeSH
- Influenza Vaccines * adverse effects MeSH
- Influenza A Virus, H1N1 Subtype * genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
