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

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
• 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

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

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

BACKGROUND: The successive editions of the International Classification of Sleep Disorders (ICSD) reflect the evolution of the concepts of various sleep disorders. This is particularly the case for central disorders of hypersomnolence, with continuous changes in terminology and divisions of narcolepsy, idiopathic hypersomnia, and recurrent hypersomnia. According to the ICSD 2nd Edition (ICSD-2), narcolepsy with cataplexy (NwithC), narcolepsy without cataplexy (Nw/oC), idiopathic hypersomnia with long sleep time (IHwithLST), and idiopathic hypersomnia without long sleep time (IHw/oLST) are four, well-defined hypersomnias of central origin. However, in the absence of biological markers, doubts have been raised as to the relevance of a division of idiopathic hypersomnia into two forms, and it is not yet clear whether Nw/oC and IHw/oLST are two distinct entities. With this in mind, it was decided to empirically review the ICSD-2 classification by using a hierarchical cluster analysis to see whether this division has some relevance, even though the terms "with long sleep time" and "without long sleep time" are inappropriate. RESULTS: The cluster analysis differentiated three main clusters: Cluster 1, "combined monosymptomatic hypersomnia/narcolepsy type 2" (people initially diagnosed with IHw/oLST and Nw/oC); Cluster 2 "polysymptomatic hypersomnia" (people initially diagnosed with IHwithLST); and Cluster 3, narcolepsy type 1 (people initially diagnosed with NwithC). CONCLUSIONS: Cluster analysis confirmed that narcolepsy type 1 and polysymptomatic hypersomnia are independent sleep disorders. People who were initially diagnosed with Nw/oC and IHw/oLST formed a single cluster, referred to as "combined monosymptomatic hypersomnia/narcolepsy type 2."

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• narkolepsie klasifikace   diagnóza   MeSH
• polysomnografie MeSH
• poruchy nadměrné spavosti klasifikace   diagnóza   MeSH
• shluková analýza MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Narcolepsy-cataplexy (N-C) is a focal neurodegenerative disease with a genetic predisposition and autoimmune etiology; the pathogenesis of narcolepsy without cataplexy (Nw/oC) is less clear. One hundred and forty eight patients underwent clinical face-to face interviews, polysomnography, multiple sleep latency testing and HLA-DQB1*0602 typing. The cohort was divided into four age groups: children and adolescents under 19 years (N = 31), adults aged 20-39 years (N = 51), 40-59 years (N = 28) and over 60 years (N = 38). N-C was found in 93 adults (79.5 %) compared with 16 pediatric patients (51.6 %) (p < 0.01), suggesting that at least some of the children were candidates for developing cataplexy in the future. Statistical evaluation showed an increasing age-related proportion of associated sleep disorders-obstructive sleep apnea, periodic leg movements and restless leg syndrome (p < 0.001). Nw/oC patients showed sleep comorbidities less frequently than N-C group. A close connection with N-C was found particularly in REM behavior disorder (RBD) (p < 0.05). RBD affected a third of the patients in the youngest as well as in the oldest groups. However, association with other sleep disorders had no significant effect on nocturnal sleep (with the exception of obstructive sleep apnea), and the sleep comorbidities under study had no noticeable effect on daytime sleepiness.

• MeSH
• dítě MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• narkolepsie diagnóza   epidemiologie   patofyziologie   MeSH
• polysomnografie metody   MeSH
• porucha chování v REM spánku diagnóza   epidemiologie   patofyziologie   MeSH
• poruchy spánku a bdění diagnóza   epidemiologie   patofyziologie   MeSH
• průřezové studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stadia spánku fyziologie   MeSH
• syndrom neklidných nohou diagnóza   epidemiologie   patofyziologie   MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND: Narcolepsy is a life-long disease characterized by abnormal regulation of the sleep-wake cycle and increased penetration of rapid eye movement (REM) sleep. In children, narcolepsy without cataplexy is more frequently seen than in adults. The aim of our study was to evaluate clinical and polysomnographic parameters to verify if cataplexy appearing later in life can be foretold. METHODS: 30 patients (12 boys), who contracted narcolepsy before the age of 18, were enrolled. All underwent clinical examination, nocturnal polysomnography (PSG), multiple sleep latency test (MSLT), HLA-DQB1∗0602 testing and, most of them Epworth Sleepiness Scale (ESS) rating. The Mann-Whitney rank and Fisher's tests were used for statistical analysis. RESULTS: Narcolepsy without cataplexy (NwC) was diagnosed in 40% of the patients. The mean age at the first symptoms was 14.0 ± 3.0, at diagnosis 15.6 ± 3.1 years. Narcolepsy was accompanied by hypnagogic hallucinations in 15 and sleep paralysis in 12 patients. Frequent symptoms were sleep inertia during awakening, REM behavior symptoms, behavioral and serious school problems. BMI was higher in patients with narcolepsy-cataplexy (N-C). A high ESS score was indicative of excessive daytime sleepiness (17.1 ± 2.5). Mean MSLT sleep latency was 4.0 ± 3.1 min with 3.2 ± 1.4 sleep onset REM periods (SOREMs) with no difference between the two study groups. HLA typing revealed no differences either. The N-C group showed a higher degree of wakefulness and superficial non-REM (NREM) stage 1 with a lower NREM stage 3 during PSG. CONCLUSION: Narcolepsy in childhood leaves very little scope for the prediction of cataplexy later in life.

• MeSH
• bdění fyziologie   MeSH
• dítě MeSH
• halucinace diagnóza   MeSH
• kohortové studie MeSH
• lidé MeSH
• mladiství MeSH
• narkolepsie diagnóza   MeSH
• parasomnie spojené s REM spánkem diagnóza   MeSH
• polysomnografie metody   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• spánek REM fyziologie   MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Nadměrnou denní spavostí (excessive daytime sleepiness, EDS) trpí necelých 5 % populace a EDS představuje proto závažný společenský problém. Nejvyšší podíl na snížené vigilitě během dne však mají poruchy nočního spánku (syndrom spánkové apnoe, syndrom neklidných nohou, případně insomnie), nedodržování správné životosprávy a hygieny spánku, lékové a jiné závislosti (alkohol, drogy). Přehled je zaměřen na nově zavedenou mezinárodní klasifikaci centrálních hypersomnií, mezi které je řazena narkolepsie s kataplexií, narkolepsie bez kataplexie, skupina idiopatických a rekurentních hypersomnií a sekundární formy hypersomnií, které mohou být průvodním projevem organického i neorganického postižení CNS. Stručně je uvedena historie jednotlivých klinických jednotek s významem českého přínopro mezinárodní vědecké poznání, jejich epidemiologie a patofyziologie. Podrobněji jsou uvedeny diagnostické a vyšetřovací postupy, klinický obraz i diferenciální diagnostika. Důležitou úlohu v diagnostice obtíží má kromě podrobné anamnézy a subjektivního škálování objektivizace EDS, zejména test mnohoČetné spánkové latence (multiple sleep latency test, MSLT) a určení některých biochemických a imunologických markerů. Deficit hladiny hypokretinu/orexinu v mozkomíšním moku a přítomnost haplotypu HLA-DQB1*0602 je diagnostickou podporou narkolepsie-kataplexie. V současné době je nejosvědčenějším lékem při léčbě EDS a zejména narkolepsie modafinil a nadějným lékem k ovlivnění kataplexie je oxybát sodný.

Nearly 5% of population suffer from excessive daytime sleepiness (EDS), thus making the condition a major social problem. However, decreased daytime wakefulness is mainly due to nocturnal sleep disorders (sleep apnoea syndrome, restíess legs syndrome and/or insomnia), failure to adhere to a healthful regimen and sleep hygiene, drug and other types of addiction (alcohol, narcotics). The survey is directed to the newly introduced international classification of central hypersomnias including narcolepsy with and without cataplexy, a group of idiopathic and recurrent hypersomnias and secondary hypersomnias, possibly concomitant with organic and inorganic CNS involvement. The history of diagnostic and examination procedures, clinical picture and differential diagnostics has been briefly presented. Besides detailed history-taking and subjective scoring for EDS objectivization, a major role in diagnosing sleep problems is played chiefly by MSLT (multiple sleep latency test) and tests for some biochemical and immunological markers. The decreased levels of hypocretin/orexin in the cerebrospinal fluid and the presence of HLA-DQB 1*0602 haplotype facilitate the diagnosis of narcolepsy-cataplexy. Modafinil is currently the best-tried drug for treating EDS and especially narcolepsy while sodium oxybate is a promising medicament for the management of cataplexy.

• MeSH
• benzhydrylové sloučeniny terapeutické užití   MeSH
• idiopatická hypersomnie MeSH
• kataplexie MeSH
• lidé MeSH
• narkolepsie diagnóza   patofyziologie   terapie   MeSH
• oxybát sodný terapeutické užití   MeSH
• poruchy nadměrné spavosti diagnóza   patofyziologie   terapie   MeSH
• poruchy spánku a bdění epidemiologie   patofyziologie   MeSH
• průzkumy a dotazníky klasifikace   využití   MeSH
• Check Tag
• lidé MeSH