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1.
Prion ; 13(1): 77-82, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30922182

RESUMO

The aim of the presented study was to reveal the frequency of insomnia spells in E200K genetic Creutzfeldt-Jakob disease (gCJD) patients. Clinical records of 22 subjects diagnosed with E200K gCJD were retrospectively reviewed. The patients w/wo insomnia (n = 4, 18%/n = 18, 82%) did not differ in age, sex and the duration of the symptomatic phase. Analysis of the clinical features in the groups yielded differences in the clinical signs in the early phase of the disorder, proportion of homozygotes (Met/Met) at codon 129, MRI changes in the thalamus and the typical EEG abnormality. The study suggests that apart from traditional clinical features, the insomnia is not a rare early symptom in phenotype of E200K gCJD based on early thalamic involvement.


Assuntos
Síndrome de Creutzfeldt-Jakob/complicações , Síndrome de Creutzfeldt-Jakob/genética , Mutação Puntual , Proteínas Priônicas/genética , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/genética , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos
3.
Sci Rep ; 8(1): 10628, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30006563

RESUMO

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.

4.
Front Neurol ; 9: 376, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29887829

RESUMO

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by repeated episodes of REM sleep-related vocalizations and/or complex motor behaviors. Definite diagnosis of RBD is based on history and polysomnography, both of which are less accessible due to the lack of trained specialists and high cost. While RBD may be associated with disorders like narcolepsy, focal brain lesions, and encephalitis, idiopathic RBD (iRBD) may convert to Parkinson's disease (PD) and other synucleinopathies in more than 80% of patients and it is to date the most specific clinical prodromal marker of PD. Identification of individuals at high risk for development of PD is becoming one of the most important topics for current PD-related research as well as for future treatment trials targeting prodromal PD. Furthermore, concomitant clinical symptoms, such as subtle motor impairment, hyposmia, autonomic dysfunction, or cognitive difficulties, in subjects with iRBD may herald its phenoconversion to clinically manifest parkinsonism. The assessment of these motor and non-motor symptoms in iRBD may increase the sensitivity and specificity in identifying prodromal PD subjects. This review evaluates the diagnostic accuracy of individual rating scales and validated single items for screening of RBD and the role and accuracy of available clinical, electrophysiological, imaging, and tissue biomarkers in predicting the phenoconversion from iRBD to clinically manifest synucleinopathies.

5.
Cent Eur J Public Health ; 26 Suppl: S32-S36, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30817870

RESUMO

OBJECTIVE: Obstructive sleep apnoea syndrome (OSAS) associated with daytime sleepiness (DS) contributes to a higher incidence of motor vehicle accidents. Validation of fitness to drive in driving license applicants, with special concern regarding OSAS accompanied by excessive DS, became mandatory under new EU legislation in January 2016. The aim of the study was to translate and validate the recommended questionnaire to screen for OSAS (Q-OSAS) in the Slovak population. No data on any Q-OSAS validation has previously been published. METHODS: The translated Q-OSAS was administered to 311 Slovak patients prior to a planned overnight polysomnography. The diagnostic accuracy of the Q-OSAS in OSAS with an apnoea-hypopnoea index of 15 or more/h of sleep was evaluated by calculating the area under the ROC curve. RESULTS: The sensitivity and specificity of the cut-off at 10 points for the Q-OSAS was 57% and 67%, respectively, with an increase of sensitivity and a decrease of specificity with a lowering of the cut-off values. Excluding the Epworth Sleepiness Scale (ESS) score from the final statistics yielded the best sensitivity (77%), specificity (50%), and an area under the ROC curve (0.637) for the cut-off value of 8 points (an equivalent of 10 points with the full version of the Q-OSAS). CONCLUSION: The Q-OSAS is an appropriate screening tool to facilitate the screening of subjects potentially at risk from moderate and severe OSAS. A modified two-step interpretation of the Q-OSAS in Slovakia yielded the best sensitivity, and in the future could promote evaluation of sleepiness in sleep and wake disorders other than OSAS for fitness to drive.


Assuntos
Programas de Rastreamento/instrumentação , Polissonografia/métodos , Psicometria/estatística & dados numéricos , Apneia Obstrutiva do Sono/diagnóstico , Inquéritos e Questionários/normas , Humanos , Reprodutibilidade dos Testes , Sono , Eslováquia , Tradução
6.
Cent Eur J Public Health ; 26 Suppl: S37-S41, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30817871

RESUMO

OBJECTIVES: An extraordinary incidence of genetic Creutzfeldt-Jakob disease (gCJD) appearing in clusters in the Slovak Republic was described in the 1990's. The aim of the study was to analyse data of CJD cases obtained from surveillance in Eastern Slovakia (ES) (2004-2016), the region outside the described geographical clusters. METHODS: The database set in the project was the source for epidemiological and clinical analysis of CJD cases. RESULTS: The incidence of CJD in ES (2004-2016) was 1.7/million person-years (95% CI 1-2.4); the incidence increase in the last five years (2012-2016) was comparable to the whole country. Twenty seven of 29 reported CJD cases were available for analysis (mean age 59 years, F/M 15/12). The proportion of gCJD (E200K mutation) cases remained dominant (78%), with 9 familiar cases originating in 4 families. Analysis of the clinical features revealed shorter duration of the symptomatic phase in sporadic CJD (sCJD) (3.4 months) versus gCJD (5.15 months). Cognitive/behavioural changes, insomnia, and sensory disturbance were more pronounced in the early symptoms of gCJD. Periodic EEG discharges were more frequent in sCJD (83%) than gCJD (56%), all 19 available MR findings were CJD specific and localisation of abnormalities varied amongst the CJD forms. CONCLUSIONS: The surveillance of CJD in ES (2004-2016) showed an increased incidence of CJD in ES, reaching the incidence rate of the whole country, with a permanent proportion of 70% gCJD cases based on the E200K mutation. Clinical, electrophysiological and MR features of sCJD and gCJD cases were in conformity with already published data. Epidemiological analysis of CJD in ES shows increasing detection of CJD but also suggests that current routine surveillance systems for CJD may underestimate the true burden of disease, especially sporadic cases in Slovakia.


Assuntos
Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/genética , Encefalopatia Espongiforme Bovina , Príons/genética , Adolescente , Adulto , Idoso , Animais , Bovinos , Síndrome de Creutzfeldt-Jakob/epidemiologia , Feminino , Genótipo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Vigilância da População , Eslováquia/epidemiologia
7.
Cent Eur J Public Health ; 26 Suppl: S51-S55, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30817874

RESUMO

OBJECTIVE: The aim of the study was to evaluate the seroprevalence of West Nile virus (WNV) among the variable population of Eastern Slovakia. METHODS: A serologic survey was conducted using 464 serum samples. The basic demographic, epidemiologic and clinical information was obtained for each serum sample at the time of specimen collection. The presence of antibodies against WNV was investigated using a commercial enzyme-linked immunosorbent assay (ELISA). All the ELISA positive samples were further analysed by a neutralization test with WNV and Usutu virus. RESULTS: Three serum samples (0.65%) from the participants (N = 464) were considered positive for antibodies to WNV. A 29-year-old female was repeatedly exposed to mosquito bites working as a shepherdess and participating in many outdoor activities. Two other females (61 and 76 years old) were treated at the Department of Neurology due to monoparesis of the upper extremity, vertigo; both had a significant epidemiological history with frequent tick and mosquito bites and stay in an endemic region. CONCLUSIONS: Although there was no evidence of WNV infection in the Slovak Republic, the epidemiological situation in the neighbouring countries warrants vigilance and appropriate measures, including the introduction of specific diagnostic tools into clinical practice. The constant monitoring of birds and mosquitoes also seems necessary.


Assuntos
Febre do Nilo Ocidental/diagnóstico , Vírus do Nilo Ocidental/isolamento & purificação , Animais , Anticorpos Antivirais , Culicidae , Ensaio de Imunoadsorção Enzimática , Feminino , Estudos Soroepidemiológicos , Eslováquia/epidemiologia , Febre do Nilo Ocidental/epidemiologia
8.
Cent Eur J Public Health ; 26 Suppl: S56-S60, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30817875

RESUMO

OBJECTIVE: The aim of this seroepidemiological study was to determine the current prevalence of antibodies against tick-borne encephalitis virus (TBEV) in the representative group of Slovak population with included potential risk factors for TBEV. METHODS: Representative group consisted of 428 persons (also with possible exposure to risk factors for tick bite or raw milk consumption). Serum samples were screened by commercial enzyme-linked immunosorbent assay (ELISA). The persons involved in the study completed questionnaires with general demographic, epidemiological and clinical data. During the analysis, we used linear regression to interpret the influence between selected variables. RESULTS: We detected 1.2% prevalence of positive IgG and 1.6% prevalence of positive IgM antibodies in all tested groups. Our results also confirmed that the following risk factors such as tourism, hunting, fishing, and consumption of raw milk are significantly associated with the prevalence of specific antibodies against TBEV. CONCLUSION: The results of seroprevalence obtained by this study confirm the possibility of infection with TBEV among respondents exposed to possible contact with ticks.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Encefalite Transmitidos por Carrapatos/imunologia , Encefalite Transmitida por Carrapatos/imunologia , Imunoglobulina G/sangue , Adulto , Estudos Transversais , Vírus da Encefalite Transmitidos por Carrapatos/genética , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/epidemiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Eslováquia/epidemiologia
9.
Cent Eur J Public Health ; 26 Suppl: S61-S66, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30817876

RESUMO

OBJECTIVE: The aim of the presented cross-sectional seroepidemiological study was to determine the current presence of antibodies against B. burgdorferi s.l. in the groups of Slovak population, and to identify potential risk factors to Lyme borreliosis. METHODS: A group of 261 adults (patients from the Neurological Clinic with possible symptoms of LB and healthy persons with possible working exposure to tick bite: gardeners and soldiers working in afforested areas) were examined in order to assess the seroprevalence of anti-Borrelia antibodies. Sera were screened by commercial enzyme-linked immunosorbent assay (ELISA). The respondents completed questionnaires with general demographic, epidemiological and clinical data. RESULTS: We detected 17.2% presence of positive IgG and 5.7% presence of positive IgM antibodies in all investigated groups. Our results confirmed that the following risk factors such as age and gender are significantly associated with the presence of positive specific antibodies against investigated disease. CONCLUSION: The results of seroprevalence obtained in the present study confirm the possibility of infection with B. burgdorferi among respondents exposed to contact with ticks.


Assuntos
Borrelia burgdorferi/isolamento & purificação , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Doença de Lyme/diagnóstico , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Humanos , Doença de Lyme/sangue , Doença de Lyme/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Eslováquia/epidemiologia
10.
Cent Eur J Public Health ; 26 Suppl: S67-S71, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30817877

RESUMO

OBJECTIVE: Lyme disease (LD) is chronic, multi-system zoonosis transmitted by ticks, and LD aetiological agents are spirochetes of the Borrelia burgdorferi sensu lato complex. The aim of the cross-sectional study was to analyze the LD incidence on the basis of the presence of specific antibodies in the serum of patients in Eastern Slovakia, and to compare the results of serological ELISA and immunoblot assays. METHODS: Venous blood with questionnaires was obtained by field sampling of respondents from Eastern Slovakia. Overall, we examined 537 human sera by the ELISA and for confirmation we tested all positive IgG antibodies against the Borrelia immunoblot assay. RESULTS: Our results confirmed the high serum prevalence of anti-Borrelia antibodies (17.9% for IgG), while the immunoblot seropositive test was confirmed in 69.8% of responders from ELISA IgG positive sera. Positive antibodies of the IgM class were found in 7.6% of the population under study. Most commonly found were antibodies against VlsE (80.2%), p41 (66.7%), p18 (56.3%), p100 (41.7%), p58 (31.3%), and p39 (30.2%). CONCLUSION: It should be noted that detection of antibodies against B. burgdorferi s.l. is only an indirect evidence of the presence of this bacterium in the development of clinical signs of LD in humans. Laboratory LD tests should be performed in accordance with valid standards, positive and uncertain results must be confirmed by the Western Blot/Immunoblot assay.


Assuntos
Grupo Borrelia Burgdorferi/isolamento & purificação , Borrelia burgdorferi/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Doença de Lyme/diagnóstico , Doença de Lyme/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Grupo Borrelia Burgdorferi/classificação , Criança , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Humanos , Incidência , Doença de Lyme/sangue , Doença de Lyme/microbiologia , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Eslováquia/epidemiologia
11.
J Parkinsons Dis ; 7(3): 481-489, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28387681

RESUMO

BACKGROUND: Gastrointestinal symptoms are a well-recognized and common premotor feature of Parkinson's disease (PD). Moreover, multiple studies have assessed the value of colonic α-synuclein as a potential marker of prodromal PD. Recently, the International Parkinson and Movement Disorders Society (MDS) defined research criteria for prodromal PD. OBJECTIVE: The aim of our study was to test the MDS research criteria in patients undergoing diagnostic colonoscopies as potential candidates for inclusion in prospective trials evaluating colonic biopsies as a potential biomarker of prodromal PD. METHODS: We evaluated elderly patients without manifest parkinsonism undergoing diagnostic colonoscopies. During the study we assessed all risks and prodromal markers of the MDS research criteria, excluding radiotracer imaging and genetic testing. RESULTS: The mean age of the 100 enrolled patients was 61.6±9.7 years; 42 were men. The most common prodromal marker in our cohort was constipation (40%), followed by MDS-UPDRS part III scores of >6 points, excluding action tremor items (39%) and hyposmia (37%). Substantia nigra hyperechogenicity was identified in 9%, and polysomnography confirmed REM sleep behavior disorder in 2% of the patients. Five of the 100 enrolled patients (5%) fulfilled the criteria for probable prodromal PD, while another 3 patients met the 50% probability threshold. CONCLUSIONS: Our findings suggest, that the prevalence of prodromal PD in patients undergoing diagnostic colonoscopies may be higher compared to the general elderly population, although this should be confirmed in further studies including also matched controls not undergoing colonoscopy. The real prevalence of prodromal PD in this cohort will have to be confirmed in longitudinal follow-up. Patients undergoing diagnostic colonoscopies may be good candidates for multistep screening and inclusion in prospective trials.


Assuntos
Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Prevalência , Sintomas Prodrômicos , Estudos Prospectivos
12.
Prague Med Rep ; 117(2-3): 81-89, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27668524

RESUMO

Narcolepsy-cataplexy (NC) is a chronic neurological disease with suggested autoimmune etiopathogenesis. Nicotine stimulates central nervous system and smoking increases the risk of autoimmune diseases. Assessment of smoking habits and its correlation to clinical parameters among 87 adult NC patients (38 male, 49 female) included night polysomnography and multiple sleep latency test. In our sample, 43.7% NC patients were regular smokers, and 19.5% former smokers compared to 22.2%, and 12.6%, respectively, in the general population. Patients started to smoke in the mean age of 20.0 (SD ±6.0) years. 72.2% of NC smokers started to smoke before the onset of NC and the mean of the delay between smoking onset and NC onset was 9.1 (±5.8) years. We found a direct correlation between smoking duration and the number of awakenings, duration of N1 sleep, REM sleep latency, and apnoea/hypopnoea index (AHI), and, on the contrary, indirect correlation between smoking duration and N3 sleep duration, showing that smoking duration consistently correlates with sleep macrostructure. Smoking is highly prevalent in NC and has relationship with clinical features of NC.


Assuntos
Cataplexia/epidemiologia , Narcolepsia/epidemiologia , Fumar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cataplexia/diagnóstico , Cataplexia/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Comorbidade , República Tcheca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Narcolepsia/diagnóstico , Narcolepsia/tratamento farmacológico , Polissonografia , Prevalência , Fatores de Risco , Síndromes da Apneia do Sono/epidemiologia , Adulto Jovem
13.
J Sleep Res ; 25(3): 32017 Apr, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26809504

RESUMO

Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials.


Assuntos
Bases de Dados Factuais , Narcolepsia , Sistema de Registros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cataplexia/tratamento farmacológico , Cataplexia/epidemiologia , Bases de Dados Factuais/normas , Europa (Continente)/epidemiologia , Feminino , Humanos , Disseminação de Informação , Internet , Masculino , Pessoa de Meia-Idade , Narcolepsia/tratamento farmacológico , Narcolepsia/epidemiologia , Fenótipo , Vigilância de Produtos Comercializados , Estudos Prospectivos , Controle de Qualidade , Doenças Raras/tratamento farmacológico , Doenças Raras/epidemiologia , Sistema de Registros/normas , Adulto Jovem
14.
Sleep ; 39(3): 581-7, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26518595

RESUMO

STUDY OBJECTIVES: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. METHODS: HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4,043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. RESULTS: HLA-A*11:01 (OR = 1.49 [1.18-1.87] P = 7.0*10(-4)), C*04:01 (OR = 1.34 [1.10-1.63] P = 3.23*10(-3)), and B*35:01 (OR = 1.46 [1.13-1.89] P = 3.64*10(-3)) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr(9) (OR = 1.32 [1.15-1.52] P = 6.95*10(-5)) and HLA-C-Ser(11) (OR = 1.34 [1.15-1.57] P = 2.43*10(-4)). CONCLUSIONS: Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons.


Assuntos
Alelos , Linfócitos T CD8-Positivos/imunologia , Cataplexia/genética , Cataplexia/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Neurônios/imunologia , Neurônios/patologia , Estudos de Casos e Controles , Cataplexia/patologia , Epitopos/imunologia , Europa (Continente)/etnologia , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Cadeias beta de HLA-DQ/genética , Haplótipos/genética , Haplótipos/imunologia , Humanos , Desequilíbrio de Ligação , Neurônios/metabolismo , Razão de Chances , Orexinas/imunologia , Orexinas/metabolismo , Linfócitos T Citotóxicos/imunologia
16.
Sleep ; 37(1): 19-25, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24381371

RESUMO

STUDY OBJECTIVE: Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. DESIGN: Retrospective case-control study. SETTING: A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. PATIENTS AND PARTICIPANTS: For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. MEASUREMENTS AND RESULTS: None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified. CONCLUSION: An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.


Assuntos
Cataplexia/genética , Predisposição Genética para Doença/genética , Cadeias beta de HLA-DQ/genética , Narcolepsia/genética , Alelos , Desoxirribonuclease I/metabolismo , Europa (Continente)/epidemiologia , Europa (Continente)/etnologia , Grupo com Ancestrais do Continente Europeu/genética , Exoma/genética , Estudo de Associação Genômica Ampla , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/administração & dosagem , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Estudos Retrospectivos , Vacinação
17.
J Sleep Res ; 22(5): 482-95, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23496005

RESUMO

The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.


Assuntos
Cataplexia/genética , Cataplexia/fisiopatologia , Estudo de Associação Genômica Ampla , Polissonografia , Adulto , Fatores Etários , Idade de Início , Envelhecimento , Índice de Massa Corporal , Cataplexia/diagnóstico , Cataplexia/psicologia , Diagnóstico Tardio , Europa (Continente) , Feminino , Predisposição Genética para Doença , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Masculino , Neuropeptídeos/líquido cefalorraquidiano , Orexinas , Análise de Componente Principal , Estudos Retrospectivos , Caracteres Sexuais , Fatores Sexuais , Fases do Sono/fisiologia , Fatores de Tempo , Adulto Jovem
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