Narcolepsy is a rare life-long disease that exists in two forms, narcolepsy type-1 (NT1) or type-2 (NT2), but only NT1 is accepted as clearly defined entity. Both types of narcolepsies belong to the group of central hypersomnias (CH), a spectrum of poorly defined diseases with excessive daytime sleepiness as a core feature. Due to the considerable overlap of symptoms and the rarity of the diseases, it is difficult to identify distinct phenotypes of CH. Machine learning (ML) can help to identify phenotypes as it learns to recognize clinical features invisible for humans. Here we apply ML to data from the huge European Narcolepsy Network (EU-NN) that contains hundreds of mixed features of narcolepsy making it difficult to analyze with classical statistics. Stochastic gradient boosting, a supervised learning model with built-in feature selection, results in high performances in testing set. While cataplexy features are recognized as the most influential predictors, machine find additional features, e.g. mean rapid-eye-movement sleep latency of multiple sleep latency test contributes to classify NT1 and NT2 as confirmed by classical statistical analysis. Our results suggest ML can identify features of CH on machine scale from complex databases, thus providing 'ideas' and promising candidates for future diagnostic classifications.

• MeSH
• biologické modely * MeSH
• databáze faktografické statistika a číselné údaje   MeSH
• datové soubory jako téma MeSH
• dospělí MeSH
• interpretace statistických dat MeSH
• lidé MeSH
• mladý dospělý MeSH
• narkolepsie klasifikace   diagnóza   patofyziologie   MeSH
• polysomnografie statistika a číselné údaje   MeSH
• řízené strojové učení * MeSH
• ROC křivka MeSH
• spánek REM fyziologie   MeSH
• spánková latence fyziologie   MeSH
• stochastické procesy MeSH
• vzácné nemoci klasifikace   diagnóza   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: There are limited data available on regional differences in the diagnosis and management of narcolepsy. In order to better understand worldwide trends in clinical assessment and management of narcolepsy, a survey of health-care providers was conducted by the World Sleep Society Narcolepsy task force. METHODS: A total of 146 surveys that included items on the diagnosis and management of narcolepsy were completed by practitioners representing 37 countries. RESULTS: Most of the participants were from Europe, North America, Oceania, Asia and Latin America. A consistent approach to applying the diagnostic criteria of Narcolepsy was documented with the exception of measurement of CSF hypocretin-1, which has limited availability. While the majority of practitioners (58%) reported not using the test, 1% indicated always evaluating CSF hypocretin-1 levels. There was much variability in the availability of currently recommended medications such as sodium oxybate and pitolisant; modafinil and antidepressants were the most commonly used medications. Amphetamines were unavailable in some countries. CONCLUSION: The results of the study highlight clinical and therapeutic realities confronted by worldwide physicians in the management of narcolepsy. While the diagnostic criteria of narcolepsy rely in part on the quantification of CSF hypocretin-1, few physicians reported having incorporated this test into their routine assessment of the condition. Regional differences in the management of narcolepsy appeared to be related to geographic availability and expense of the therapeutic agents.

• Klíčová slova
• CSF hypocretin-1, HLA DQB1∗0602, MSLT, Narcolepsy type-1, Narcolepsy type-2, Narcolepsy—pharmacotherapy,
• MeSH
• lidé MeSH
• narkolepsie * diagnóza   farmakoterapie   MeSH
• orexiny MeSH
• péče o pacienta MeSH
• polysomnografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Asie MeSH
• Evropa MeSH
• Severní Amerika MeSH
• Názvy látek
• orexiny MeSH

A 69-year-old male developed symptoms typical of the diagnosis of narcolepsy type 1 without any previous triggering events. First, daytime sleepiness occurred, soon followed by cataplexy. Nocturnal polysomnography revealed rapid eye movement (REM) sleep behavior disorder, a apnea-hypopnea index of 25.8 events/h, and no sleep-onset REM. Multiple Sleep Latency Test showed a mean sleep latency of 2.1 min and REM sleep in 3 tests. HLA DQB1*06:02 was positive and hypocretin-1 in cerebrospinal fluid unmeasurable. A treatment with 50 mg clomipramine controlled the cataplexy; excessive daytime sleepiness was sufficiently managed by repeated naps. The administration of 0.25 mg of clonazepam subjectively improved REM sleep behavior disorder. Bilevel Positive Airway Pressure improved the apnea-hypopnea index without important influence on sleepiness. Our unique case demonstrates that even elderly subjects can develop narcolepsy type 1.

• Klíčová slova
• Elderly, Narcolepsy with cataplexy, Rare case,
• Publikační typ
• časopisecké články MeSH
• kazuistiky 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."

• Klíčová slova
• Cluster analysis, Factor analysis, Idiopathic hypersomnia, Narcolepsy type 1, 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

BACKGROUND: Childhood narcolepsy is associated with various emotional, behavioural and cognitive dysfunctions as well as with psychiatric and neurodevelopmental disorders: anxiety, depression, attention deficit hyperactivity disorder and psychosis. A relationship between these conditions is unclear - comorbidity or similar pathophysiological mechanisms can be suggested. OBJECTIVE: We reported four children with narcolepsy type 1 (NT1) and autism spectrum disorder (ASD) - Asperger syndrome (AS). RESULTS AND CONCLUSION: To the best of our knowledge co-occurrence of NT1 and AS has not been described in the literature as noted in this report.

• Klíčová slova
• Asperger syndrome, Autism spectrum disorders, Comorbidity, Hypocretin, Narcolepsy type 1,
• MeSH
• antidepresiva terapeutické užití   MeSH
• Aspergerův syndrom diagnóza   MeSH
• deprese diagnóza   farmakoterapie   MeSH
• dítě MeSH
• hyperkinetická porucha diagnóza   MeSH
• komorbidita * MeSH
• lidé MeSH
• methylfenidát aplikace a dávkování   MeSH
• narkolepsie komplikace   MeSH
• poruchy nadměrné spavosti diagnóza   farmakoterapie   MeSH
• stadia spánku fyziologie   MeSH
• tikové poruchy diagnóza   MeSH
• úzkostné poruchy diagnóza   farmakoterapie   MeSH
• věk při počátku nemoci * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antidepresiva MeSH
• methylfenidát 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
• 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

Increased incidence rates of narcolepsy type-1 (NT1) have been reported worldwide after the 2009-2010 H1N1 influenza pandemic (pH1N1). While some European countries found an association between the NT1 incidence increase and the H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus itself to be linked to the increased NT1 incidence. Using robust data-driven modeling approaches, that is, locally estimated scatterplot smoothing methods, we analyzed the number of de novo NT1 cases (n = 508) in the last two decades using the European Narcolepsy Network database. We confirmed the peak of NT1 incidence in 2010, that is, 2.54-fold (95% confidence interval [CI]: [2.11, 3.19]) increase in NT1 onset following 2009-2010 pH1N1. This peak in 2010 was found in both childhood NT1 (2.75-fold increase, 95% CI: [1.95, 4.69]) and adulthood NT1 (2.43-fold increase, 95% CI: [2.05, 2.97]). In addition, we identified a new peak in 2013 that is age-specific for children/adolescents (i.e. 2.09-fold increase, 95% CI: [1.52, 3.32]). Most of these children/adolescents were HLA DQB1*06:02 positive and showed a subacute disease onset consistent with an immune-mediated type of narcolepsy. The new 2013 incidence peak is likely not related to Pandemrix as it was not used after 2010. Our results suggest that the increased NT1 incidence after 2009-2010 pH1N1 is not unique and our study provides an opportunity to develop new hypotheses, for example, considering other (influenza) viruses or epidemiological events to further investigate the pathophysiology of immune-mediated narcolepsy.

• Klíčová slova
• H1N1 influenza, childhood narcolepsy, narcolepsy,
• MeSH
• chřipka lidská * epidemiologie   prevence a kontrola   MeSH
• dítě MeSH
• dospělí MeSH
• incidence MeSH
• lidé MeSH
• mladiství MeSH
• narkolepsie * epidemiologie   etiologie   MeSH
• vakcinace MeSH
• vakcíny proti chřipce * MeSH
• virus chřipky A, podtyp H1N1 * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Asie MeSH
• Evropa MeSH
• Názvy látek
• vakcíny proti chřipce * 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: Narcolepsy is associated with altered metabolic functions. We sought to investigate the effect of narcolepsy on pregnancy and newborns. MATERIAL/METHODS: A retrospective cohort study of patients in whom the first symptoms of narcolepsy appeared before or after pregnancy. Our study included 54 women, mothers of a total of 110 children (37 with symptoms of narcolepsy before and during pregnancy, 17 developed the narcolepsy syndrome only after childbirth). With only 1 exception, none of the patients were treated with drugs during pregnancy. RESULTS: We did not find any significant differences between the 2 groups in the registered parameters of: age of mothers at delivery, history of spontaneous abortion, alcohol and nicotine consumption, medication, complications during pregnancy, symptoms of narcolepsy, weight gain during pregnancy, length of pregnancy and delivery, complications during delivery, and weight and length of the newborn. The women experiencing symptoms of narcolepsy before or during pregnancy were found to have a significantly higher total number of pregnancy complications (35.8%) than those with later onset of symptoms (9.1%), although the complications were not clinically significant. More patients in the symptomatic group tended to have impaired glucose tolerance or type 2 diabetes, compared to the asymptomatic group. CONCLUSIONS: The study revealed no clinically relevant adverse effects of narcolepsy on pregnancy, childbirth or the newborn.

• MeSH
• dospělí MeSH
• kohortové studie MeSH
• komplikace těhotenství epidemiologie   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• narkolepsie komplikace   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• věkové faktory MeSH
• výsledek těhotenství epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Slovenská republika epidemiologie   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