Narcolepsy type-1
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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
- práce podpořená grantem MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Narkolepsie typ 1 (NT1), narkolepsie typ 2 (NT2) a idiopatická hypersomnie (IH) mají hlavní symptom centrální hypersomnii (CH). Etiopatofyziologie NT1 je spojena s deficitem hypokretinu autoimunitního původu. Etiopatofyziologie NT2 a IH je neznámá. Jsou pochybnosti o nezávislosti NT2 a IH a o jejich dlouhodobém průběhu. Střevní microbiota má vliv na mozkové funkce a chování buď přímo přes tvorbu mediátorů nebo nepřímo prostřednictvím autoprotilátek proti vybraným neuronům. Lze proto vyslovit hypotézu, že microbiota hraje roli v etiopatofyziologii nemocí s CH a může modifikovat aktuální intenzitu samotné hypersomnie. Nemocní s CH a zdravé kontroly budou klinicky vyšetřeni (včetně dlouhodobého vývoje NT2 a IH). Jejich stolice bude geneticky analyzována s cílem definovat mikrobiom střevní mikrobioty. Bude pátráno po autoprotilátkách. Výsledky budou vzájemně korelovány. Tento výzkum má osvětlit patofyziologii nemocí s CH a také má pomoci v doporučeních nemocným a může otevřít nové směry léčby.; Narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) have as a main symptom central hypersomnia (CH). The etiopathophysiology of NT1 is related to the hypocretin deficiency of autoimmune origin. The etiopathophysiology of NT2 and IH is unknown. There are doubts on the independence of NT2 and IH and their long-term course. The gut microbiota has an impact on brain functions and behavior either directly by mediators’ production or indirectly via autoantibodies against selected neurons. This evokes the hypothesis that microbiota has a role in etiopathophysiology of diseases with CH and may modify actual intensity of hypersomnia itself. Patients with CH and healthy controls will be clinically examined (including the long-term evolution of NT2 and IH). Their stools will be genetically analyzed in attempt to define the microbiome of the gut microbiota. The autoantibodies will be searched in their blood. The results will be mutually correlated. This research may elucidate the pathophysiology of CH disorders as well as may help to counselling the patients and fina
- Klíčová slova
- autoimmunity, mikrobiom, microbiome, autoprotilátky, autoantibodies, idiopatická hypersomnie, Idiopathic hypersomnia, autoimunita, elderly, extrakce DNA, vysoce výkonné sekvenování (HTS), funkce střevní bariéry, DNA extraction, high throughput sequencing (HTS), stáří, mikrobiota, microbiota, Narkolepsie typ 1 - narkolepsie s kataplexií, narkolepsie typ 2 - narkolepsie bez kataplexie, centrální hypersomnie, vývoj nemoci, Narcolepsy type 1 - narcolepsy with cataplexy, narcolepsy type 2 - narcolepsy without cataplexy, central hypersomnia, intesintal barrier function, disease evolution,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
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
- 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
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
- 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
Cíl: Studie si kladla za cíl ověřit vhodnost použití Škály tíže narkolepsie (Narcolepsy Severity Scale; NSS) jako základního klinického nástroje pro stanovení subjektivní tíže onemocnění u pacientů s narkolepsií typu 1 (NT1) v ČR. Soubor a metodika: Celkem 78 pacientů ze 2 spánkových center s diagnózou NT1 (29 mužů, 49 žen, průměrný věk 36,1 ± 11,7 let, rozmezí 18–71 let, z toho léčených n = 51) vyplnilo škálu NSS sestávající z 15 otázek zaměřených na výskyt, frekvenci a dopad na denní aktivity všech hlavních narkoleptických příznaků. Současně byli instruováni vyplnit Epworthskou škálu spavosti (Epworth Sleepiness Scale; ESS), Škálu tíže únavy (Fatigue Severity Scale; FSS), Škálu hodnocení úzkosti a deprese při hospitalizaci (Hospital Anxiety and Depression Rating Scale; HADS) a zkrácenou verzi Dotazníku kvality života (Quality of Life Questionnaire; SF-36). Výsledky: Škála NSS vykazuje dobrou vnitřní konzistenci dotazníku pomocí koeficientu Cronbachova a, která je pro celou kohortu pacientů s NT1 0,80, pro skupinu léčených pacientů 0,79 a pro skupinu neléčených pacientů 0,82. Keiser-Meyer-Olkinův index pro celou kohortu je 0,73, což potvrzuje dostatečnou strukturální validitu dotazníku. Nebyl zjištěn signifikantní rozdíl ve skóre NSS léčených a neléčených pacientů, nicméně byla potvrzena korelace celkového skóre NSS s ESS (ρ = 0,61; p < 0,0001) a FSS (ρ = 0,4438; p < 0,0001). Závěr: NSS představuje vhodný a snadno aplikovatelný klinický nástroj ke stanovení subjektivní tíže onemocnění, dobře vystihuje hlavní narkoleptické příznaky a hodnotí jejich vliv na denní aktivity.
Aim: The aim of the study was to verify the applicability of the Narcolepsy Severity Scale (NSS) as a basic clinical tool for determining the subjective severity of the disease in patients with narcolepsy type 1 (NT1) in the Czech Republic. Patients and methods: A total of 78 patients from 2 sleep centers with a diagnosis of NT1 (29 men, 49 women, mean age 36.1 ± 11.7 years, range 18–71 years, N = 51 were treated) completed the NSS scale consisting of 15 questions focusing on the occurrence, frequency, and impact on daily activities of all major narcoleptic symptoms. At the same time, they were instructed to complete the Epworth Sleepiness Scale (ESS), the Fatigue Severity Scale (FSS), the Hospital Anxiety and Depression Rating Scale (HADS) and a short version of the Quality of Life Questionnaire (SF-36). Results: The NSS scale shows good internal consistency of the questionnaire using Cronbach‘s a, which is 0.80 for the whole cohort of NT1 patients, 0.79 for the treated group and 0.82 for the untreated group. The Keiser-Meyer-Olkin index for the entire cohort is 0.73, confirming sufficient structural validity of the questionnaire. There was no significant difference in the NSS scores of treated and untreated patients; however, the correlation of the total NSS score with ESS (ρ = 0.61; P < 0.0001) and FSS (ρ = 0.4438; P < 0.0001) was confirmed. Conclusions: The NSS is a convenient and practical clinical tool for determining the subjective severity of the disease, well capturing the main narcoleptic symptoms and assessing their impact on daily activities.
Cíl: Srovnání polysomnografických parametrů nočního spánku pacientů mužů s narkolepsií typu 1 ve věku nad 55 let s věkově spárovanými kontrolami. Soubor a metodika: Soubor tvořilo 17 mužů (průměrný věk 66,1 ± 8,3 let) s narkolepsií typu 1, jejichž dříve získané záznamy polysomnografického vyšetření byly porovnány z hlediska základních parametrů makrostruktury spánku a jeho základních poruch s polysomnografickými záznamy věkově spárovaných mužů (průměr 65,0 ± 6,6 let). Výsledky: Pacienti s narkolepsií typu 1 měli oproti kontrolám významně nižší procentuální zastoupení stádia NREM 3 (8 vs. 26 %; p = 0,003) a REM spánku (12 vs. 19 %; p = 0,01) a vyšší zastoupení stádia NREM 1 (17 vs. 10 %; p = 0,01). Zastoupení bdělosti (29 vs. 26 %) a stádia NREM 2 (33 vs. 30 %), průměrná latence usnutí, latence REM spánku, trvání spánku i spánková efektivita (67 ± 14 vs. 72 ± 17 %) se mezi soubory nelišily. Výskyt obstrukčních spánkových apnoí byl srovnatelný (apnoe/hypopnoe index 25 ± 26 vs. 23 ± 18). Index periodických pohybů končetinami ve spánku byl v narkoleptické skupině výrazně vyšší (46 ± 31 vs. 16 ± 22; p = 0,02) a přítomnost poruchy atonie v REM spánku (47 vs. 8 %; p = 0,002) četnější. Závěr: Muži s narkolepsií typu 1 mají signifikantně méně zastoupena stádia NREM 3 a REM, a naopak více stádia NREM 1.
Aim: The aim of this study was to compare polysomnographic parameters of nocturnal sleep in male patients with narcolepsy type 1 aged over 55 years with age-matched controls. Patients and methods: The cohort consisted of 17 men (mean age 66.1 ± 8.3 years) with narcolepsy type 1 whose previously obtained polysomnographic records were compared in terms of basic parameters of sleep macrostructure and its basic disorders with polysomnographic records of age-paired men (mean 65.0 ± 6.6 years). Results: Compared to controls, males with narcolepsy type 1 had a significantly lower percentage of NREM 3 (8 vs. 26%; P = 0.003) and REM sleep stages (12 vs. 19%; P = 0.01) and a higher presentation of NREM 1 stages (17 vs. 10%; P = 0.01). The representation of wakefulness (29 vs. 26%) and NREM 2 stages (33 vs. 30%), mean sleep latency, REM sleep latency, sleep duration, and sleep efficiency (67 ± 14 vs. 72 ± 17%) did not differ between groups. The incidence of obstructive sleep apneas was comparable (apnea-hypopnea index 25 ± 26 vs. 23 ± 18). The index of periodic limb movements during sleep was significantly higher (46 ± 31 vs. 16 ± 22; P = 0.02) and the presence of REM sleep without atonia (47 vs. 8%; P = 0.02) was more frequent in the narcoleptic group. Conclusion: Men with narcolepsy type 1 have significantly less NREM 3 and REM stages and more NREM 1 stages.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- narkolepsie * patofyziologie patologie MeSH
- polysomnografie * metody přístrojové vybavení MeSH
- poruchy spánku a bdění diagnóza MeSH
- senioři MeSH
- stadia spánku MeSH
- statistika jako téma MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
Fatigue, depression, and sleep inertia are frequently underdiagnosed manifestations in narcolepsy and idiopathic hypersomnia. Our cross-sectional study design included diagnostic interview accompanied by assessment instruments and aimed to explore how these factors influence disease severity as well as to elucidate any sex predisposition. One hundred and forty-eight subjects (female 63%) were divided into narcolepsy type 1 (NT1; n = 87, female = 61%), narcolepsy type 2 (NT2; n = 22, female = 59%), and idiopathic hypersomnia (IH; n = 39, female = 69%). All subjects completed a set of questionnaires: Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scales (HADS), Fatigue Severity Scale (FSS), and Sleep Inertia Questionnaire (SIQ). In narcoleptic subjects, questionnaire data were correlated with the Narcolepsy Severity Scale (NSS), and in subjects with idiopathic hypersomnia, with the Idiopathic Hypersomnia Severity Scale (IHSS). The highest correlation in narcoleptic subjects was found between NSS and ESS (r = 0.658; p < 0.0001), as well as FSS (r = 0.506; p < 0.0001), while in subjects with idiopathic hypersomnia, the most prominent positive correlations were found between IHSS and SIQ (r = 0.894; p < 0.0001), FSS (r = 0.812; p < 0.0001), HADS depression scale (r = 0.649; p = 0.0005), and HADS anxiety scale (r = 0.528; p < 0.0001). ESS showed an analogic correlation with disease severity (r = 0.606; p < 0.0001). HADS anxiety and depression scores were higher in females (p < 0.05 and p < 0.01), with similar results for FSS and SIQ scales (p < 0.05 for both), and a trend toward higher ESS values in females (p = 0.057). Our study illustrates that more attention should be focused on pathophysiological mechanisms and associations of fatigue, depression, as well as sleep inertia in these diseases; they influence the course of both illnesses, particularly in women.
- Publikační typ
- časopisecké články MeSH
Denná spavosť (DS) predstavuje pre postihnutého jedinca závažné riziko v podobe sťaženého pracovného uplatnenia a zníženej kvality života a v závislosti od jej príčiny aj metabolické a kardiovaskulárne následky. Práca analyzuje charakter ospalosti v závislosti od jej príčiny, diagnostické postupy a terapeutické možnosti. Na príklade piatich kazuistík poukazuje na rozdiely v klinickej manifestácii spavosti pri narkolepsii 1. typu, Kleinovom-Levinovom syndróme, epilepsii, sclerosis multiplex a osmotickom demyelinizačnom syndróme, dokladuje uplatnenie diagnostických a terapeutických možností v praxi.
Daytime sleepiness (DS) poses a serious risk to the affected individual in the form of difficult employment and reduced quality of life and, depending on its cause, also metabolic and cardiovascular consequences. The work analyzes the nature of sleepiness depending on its cause, diagnostic procedures and therapeutic options. On the example of five case reports points out the differences in clinical manifestation of sleepiness in narcolepsy type 1, Klein-Levin syndrome, epilepsy, multiple sclerosis and osmotic demyelinating syndrome, it demonstrates the application of diagnostic and therapeutic options in clinical practice.
Purpose: Narcolepsy type-1 (NT1) is a rare chronic neurological sleep disorder with excessive daytime sleepiness (EDS) as usual first and cataplexy as pathognomonic symptom. Shortening the NT1 diagnostic delay is the key to reduce disease burden and related low quality of life. Here we investigated the changes of diagnostic delay over the diagnostic years (1990-2018) and the factors associated with the delay in Europe. Patients and Methods: We analyzed 580 NT1 patients (male: 325, female: 255) from 12 European countries using the European Narcolepsy Network database. We combined machine learning and linear mixed-effect regression to identify factors associated with the delay. Results: The mean age at EDS onset and diagnosis of our patients was 20.9±11.8 (mean ± standard deviation) and 30.5±14.9 years old, respectively. Their mean and median diagnostic delay was 9.7±11.5 and 5.3 (interquartile range: 1.7-13.2 years) years, respectively. We did not find significant differences in the diagnostic delay over years in either the whole dataset or in individual countries, although the delay showed significant differences in various countries. The number of patients with short (≤2-year) and long (≥13-year) diagnostic delay equally increased over decades, suggesting that subgroups of NT1 patients with variable disease progression may co-exist. Younger age at cataplexy onset, longer interval between EDS and cataplexy onsets, lower cataplexy frequency, shorter duration of irresistible daytime sleep, lower daytime REM sleep propensity, and being female are associated with longer diagnostic delay. Conclusion: Our findings contrast the results of previous studies reporting shorter delay over time which is confounded by calendar year, because they characterized the changes in diagnostic delay over the symptom onset year. Our study indicates that new strategies such as increasing media attention/awareness and developing new biomarkers are needed to better detect EDS, cataplexy, and changes of nocturnal sleep in narcolepsy, in order to shorten the diagnostic interval.
- Publikační typ
- časopisecké články MeSH
