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AIM: The primary goal was to determine the yield of next-generation sequencing (NGS) epilepsy gene panels used for epilepsy etiology diagnosing using a multidisciplinary approach and to demonstrate the importance of genotype-phenotype correlations. The secondary goal was to evaluate the application of precision medicine in selected patients. METHODS: This single-center retrospective study included a total of 175 patients (95 males and 80 females) aged 0-19â¯years. They were examined between 2015 and 2020 using an NGS epilepsy gene panel (270 genes). A bioinformatic analysis was performed including copy number variation identification. Thorough genotype-phenotype correlation was performed. RESULTS: Out of 175 patients, described pathogenic variants or novel variants with clear pathogenic impact were identified in 30 patients (17.14%). Genotype-phenotype correlations and parental DNA analysis were performed, and genetic diagnosis was confirmed on the basis of the results in another 16 out of 175 patients (9.14%). The diagnostic yield of our study increased from 30 to 46 patients (by 53.33%) by the precise genotype-phenotype correlation. INTERPRETATION: We emphasize a complex genotype-phenotype correlation and a multidisciplinary approach in evaluating the results of the NGS epilepsy gene panel, which enables the most accurate genetic diagnosis and correct interpretation of results.
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Variações do Número de Cópias de DNA , Epilepsia , Epilepsia/diagnóstico , Epilepsia/genética , Feminino , Estudos de Associação Genética , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Mutação , Fenótipo , Estudos RetrospectivosRESUMO
The lower airways of turtles consist of the larynx, trachea and bronchi. Due to incomplete information about the anatomical structure of the lower respiratory tract in turtles, we decided to explore this topic more deeply. The material for this study included 95 turtle cadavers. Terrestrial tortoises were represented by 63 individuals from 8 species, aquatic and semi-aquatic turtles by 32 individuals from 11 species. The sex ratio was 54 females to 41 males. In addition to the anatomical autopsies and assessments of the macroscopic structures, numerous measurements were performed. The length, width and height of the larynx and trachea, and the length of the bronchi were measured. We found clinical significance in two parameters. The first one is the formation of the rima glottidis, which is significantly shorter and narrower in the aquatic turtles than in the terrestrial tortoises. It follows that for these species, we should use a smaller diameter of endotracheal cannula for intubation. The second parameter is a very short trachea in tortoises of the genus Testudo. The length of the trachea is only a few centimetres, which significantly increases the risk of intubation into one bronchus only.
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with the Dravet's syndrome phenotype are associated with the detection of a sequence variant in the SCN1A gene (alpha 1 subunit of the voltage-gated sodium channel) (2). However, sequence variants in the SCN1A gene are associated with a very broad clinical spectrum, from asymptomatic carriers to the severe myoclonic epilepsy phenotype with severe disease (3).In the presented work, we retrospectively evaluated a group of 6 patients of the Department of Pediatric Neurology of the Medical Faculty of Masaryk University and the University Hospital in Brno with a proven missense mutation. Based on the specific pathogenic sequence variant, we correlated the patient's phenotype with the location of the sequence variant in the SCN1A gene. The aim of the analysis was to verify the extent, to which the storage of a pathogenic sequence variant in the SCN1A gene corresponds to the clinical picture of the patient (Tab. 2, Fig. 2, Ref. 10). Keywords: Dravet's syndrome, sodium channel, functional analysis, prognosis.
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Epilepsias Mioclônicas , Convulsões Febris , Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/genética , Síndromes Epilépticas , Humanos , Lactente , Mutação , Mutação de Sentido Incorreto , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Fenótipo , Estudos Retrospectivos , Convulsões Febris/genética , Espasmos InfantisRESUMO
We present the case report of an unvaccinated Czech child with tetanus. The child had not received any vaccines due to its parent's refusal. The disease originated from the wound in the nose caused by a small flat battery. The typical onset of tetanus followed after two weeks, rapidly progressing to respiratory failure with the need for mechanic ventilation despite intensive treatment. The child spent five weeks in the hospital. Mild long-term sequelae persisted 5 months.
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Tétano , Criança , Família , Humanos , Tétano/diagnóstico , Toxoide TetânicoRESUMO
In 2022/2023, Europe experienced its third consecutive season of high-pathogenicity avian influenza. During this period, the Czech Republic was again severely affected. For the first time, the number of culled birds approached one million, which was three times higher than in previous seasons. In parallel to the outbreaks in poultry, mass die-offs of gulls were also observed. In the present study, we performed whole-genome sequencing and phylogenetic analysis of 137 H5N1 strains collected in the Czech Republic in 2022/2023 (94.6% of all outbreaks or locations). The analysis revealed four distinct genotypes: AB, CH, BB and AF. Phylogenetic analysis suggested that the AF genotype persisted from the previous H5N1 season without reassortment. In addition, the genotype BB, which was detected mainly in gulls, showed a noticeable strain diversity at the local level. This virus was also responsible for a single outbreak in commercially bred turkeys. Finally, an interesting spatio-temporal cluster with three co-circulating H5N1 genotypes, AB, CH and AF, was identified with no evidence of intrasubtype reassortment. Highly sensitive molecular surveillance and the timely sharing of genomic sequences and associated metadata could greatly assist in tracking the spread and detecting molecular changes associated with the increased virulence of this potentially zoonotic pathogen.
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Charadriiformes , Virus da Influenza A Subtipo H5N1 , Influenza Aviária , Doenças das Aves Domésticas , Animais , Influenza Aviária/epidemiologia , Aves Domésticas , Virus da Influenza A Subtipo H5N1/genética , Estações do Ano , Virulência , República Tcheca/epidemiologia , Filogenia , Surtos de Doenças/veterinária , Aves , Doenças das Aves Domésticas/epidemiologiaRESUMO
OBJECTIVE: We analyzed trends in patients' characteristics, outcomes, and waiting times over the last 25 years at our epilepsy surgery center situated in Central Europe to highlight possible areas of improvement in our care for patients with drug-resistant epilepsy. METHODS: A total of 704 patients who underwent surgery at the Brno Epilepsy Center were included in the study, 71 of those were children. Patients were separated into three time periods, 1996-2000 (n = 95), 2001-2010 (n = 295) and 2011-2022 (n = 314) based on first evaluation at the center. RESULTS: The average duration of epilepsy before surgery in adults remained high over the last 25 years (20.1 years from 1996 to 2000, 21.3 from 2001 to 2010, and 21.3 from 2011 to 2020, P = 0.718). There has been a decrease in rate of surgeries for temporal lobe epilepsy in the most recent time period (67%-70%-52%, P < 0.001). Correspondingly, extratemporal resections have become more frequent with a significant increase in surgeries for focal cortical dysplasia (2%-8%-19%, P < 0.001). For resections, better outcomes (ILAE scores 1a-2) have been achieved in extratemporal lesional (0%-21%-61%, P = 0.01, at least 2-year follow-up) patients. In temporal lesional patients, outcomes remained unchanged (at least 77% success rate). A longer duration of epilepsy predicted a less favorable outcome for resective procedures (P = 0.024) in patients with disease duration of less than 25 years. SIGNIFICANCE: The spectrum of epilepsy surgery is shifting toward nonlesional and extratemporal cases. While success rates of extratemporal resections at our center are getting better, the average duration of epilepsy before surgical intervention is still very long and is not improving. This underscores the need for stronger collaboration between epileptologists and outpatient neurologists to ensure prompt and effective treatment for patients with drug-resistant epilepsy.
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Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Epilepsia , Adulto , Criança , Humanos , Epilepsia/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Resultado do Tratamento , Procedimentos Neurocirúrgicos/métodosRESUMO
The key part of creating bone material for teaching is degreasing and whitening it. However, the substances used are often dangerous and toxic. We tested and compared safer methods based on two physical variables. These are light and heat. The material for our study was 45 femurs from 23 adult domestic dogs (Canis lupus f. familiaris). The bones were divided into three groups of 15 pieces according to the method used to remove muscles and ligaments from their surface. Five femurs from each group were exposed to three different light sources for 28 days-sunlight, warm light from a classical incandescent light bulb and cold light by a LED bulb. At regular intervals, the change in the colour of the bone surface and the amount of fat loss from the medullary cavity was also monitored. The best degreasing and bleaching results were achieved in macerated bones exposed to sunlight. They achieved the required condition as early as 21 days after the start of sun exposure. The biggest problem was haemoglobin, which permeated through the Haversian canals and discoloured the bone tissue. The results showed that the use of light and heat is a suitable and safe alternative to chemical methods of degreasing and bleaching bones. The disadvantage is the length of time, especially for native material.
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Clareamento Dental , Animais , Cães , Clareamento Dental/métodos , Peróxido de Hidrogênio , Osteologia , Osso e Ossos , Temperatura Alta , Ácido HipoclorosoRESUMO
To understand which morphological/anatomical parts may be responsible in artiodactyl ungulates for the clicking sound made when moving, this research focuses on the forelimb tendon apparatus where an undescribed opening in the fibrous cuff (manica flexoria), called hereafter for its shape as an "oval window" in the manica flexoria (OWMF), was detected. This oval window was found in 24 of the 25 species of four families (Camelidae, Giraffidae, Cervidae, and Bovidae) evaluated; the exception being in Bos taurus taurus (Domestic cattle). The length and width of the OWMF enabled correct species discrimination between the majority of species, but remained conservative intraspecifically, as it did not differ between the left and right side of the forelimb, third and fourth digits, or between sexes. When evaluating the shape of OWMF in individual species, and measuring its length and width, 18 out of the 24 species investigated had this window as an oval shape, the remaining 25% of species exhibited more oval-oblong shapes with either proximal or distal asymmetry. The function of the OWMF in the thoracic autopodium of most ruminant even-toed ungulates is not yet fully understood. Its most likely function is to help balance the pressure inside the ligament cuff and reduce the friction of the touching surfaces of the muscle tendons-thus facilitating the movement of the digits when walking. None of the absolute or relative OWMF parameters fit exclusively with the occurrence and distribution of knee-clicks produced by some bovids and cervids during movement, so the mechanism responsible for this sound remains cryptic from the present anatomical perspective.
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Artiodáctilos , Cervos , Animais , Bovinos , Membro Anterior , Humanos , Ligamentos , Tendões , Extremidade SuperiorRESUMO
This work presents a case series of four children diagnosed with severe cerebrovascular disease in association with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet no patient from the group met typical diagnostic criteria for multisystem inflammatory syndrome in children. Our aim was to highlight the possible vascular involvement and coagulopathies associated with SARS-CoV-2 infection in the pediatric population. Further data are needed to better understand the pathophysiological basis of this condition in children and to ensure its optimal management.
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COVID-19 , COVID-19/complicações , Criança , Humanos , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
Acute Ischemic Stroke (AIS) in children is an acute neurologic emergency associated with significant morbidity and mortality. Although the incidence of AIS in pediatric patients is considerably lower than in adults, the overall cumulative negative impact of the quality of life could be even higher in children. The age-related variable clinical presentation could result in a delay in diagnosis and could negatively influence the overall outcome. The early management should be based on early recognition, acute transfer to pediatric AIS centre, standardised approach (ABCDE), early neurologic examination together with neuroimaging (preferable Magnetic Resonance Imaging-MRI). The treatment is based on supportive therapy (normoxemia, normocapnia, normotension and normoglycemia) in combination with intravenous/intraarterial thrombolytic therapy and/or mechanical thrombectomy in selected cases. Pediatric stroke centres, together with the implementation of local stroke management protocols, could further improve the outcome of pediatric patients with AIS.
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Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. Methods: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease. Results: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. Significance: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers.
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Encefalite/imunologia , Epilepsia/terapia , Doenças Raras , Espasmos Infantis , Esclerose Tuberosa , Adulto , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Consenso , Encefalite/terapia , Epilepsias Mioclônicas/terapia , Epilepsia/fisiopatologia , Europa (Continente) , Everolimo/uso terapêutico , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Espasmos Infantis/terapia , Inquéritos e Questionários , Esclerose Tuberosa/terapiaRESUMO
PURPOSE: Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by focal seizures with dominant auditory symptomatology. We present a case report of an 18-year-old patient with acute onset of seizures associated with epilepsy. Based on the clinical course of the disease and the results of the investigation, the diagnosis of ADLTE with a proven mutation in the RELN gene, which is considered causative, was subsequently confirmed. The aim of this study was to use 3 Tesla (3â¯T) magnetic resonance imaging (MRI) and advanced neuroimaging methods in a patient with a confirmed diagnosis of ADTLE. METHODS: 3â¯T MRI brain scan and advanced neuroimaging methods were used in the standard protocols to analyzse voxel-based MRI, cortical thickness, and functional connectivity. RESULTS: Morphometric MRI analysis (blurred grey-white matter junctions, voxel-based morphometry, and cortical thickness analysis) did not provide any informative results. The functional connectivity analysis revealed higher local synchrony in the patient in the left temporal (middle temporal gyrus), left frontal (supplementary motor area, superior frontal gyrus), and left parietal (gyrus angularis, gyrus supramarginalis) regions and the cingulate (middle cingulate gyrus) as compared to healthy controls. CONCLUSIONS: Evidence of multiple areas of functional connectivity supports the theory of epileptogenic networks in ADTLE. Further studies are needed to elucidate this theory.
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PURPOSE: The aim of this study was to evaluate seizure outcome in children with hematological malignancies and PRES and to identify prognostic factors that could help manage the syndrome. METHOD: We retrospectively reviewed the report data of 21 patients diagnosed with hematological malignancy or aplastic anemia and PRES between 2008 and 2018. Basic demographic data, oncology treatment, presymptomatic hypertension before PRES manifestation, neurological status, seizure type, and EEG and MRI findings at PRES onset and at the one-year follow-up visit were studied. Patients who developed remote symptomatic seizures or epilepsy were identified. RESULTS: We included 21 children (11 females and 10 males) in the study. Sixteen patients (76.2%) were diagnosed with ALL and the rest individually with AML, CML, T-lymphoma, Burkitt lymphoma, and severe aplastic anemia. Presymptomatic hypertension (PSH) was evaluated in 19 patients and was present in 18 (94.7%). The duration was 9 h and more in 16 patients (88.8%); the severity was grade II in 12 patients (66.7%). Seizures as the initial symptom of PRES were present in 17 patients (80.9%). Four patients (19.0%) were assessed with remote symptomatic seizures. Two of them (9.5%) had ongoing seizures at the one-year follow-up visit and were diagnosed with epilepsy. The presence of gliosis on follow-up MRI indicated worse outcome with development of epilepsy (without statistical significance). CONCLUSIONS: PRES syndrome has an overall good prognosis and the evolution to epilepsy is rare. The severity and duration of PSH or seizure severity and EEG findings at PRES onsetwere not associated with worse neurological outcomes in this study.