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1.
Ideggyogy Sz ; 73(7-08): 223-229, 2020 Jul 30.
Artigo em Húngaro | MEDLINE | ID: mdl-32750238

RESUMO

Background - Based on the literature and his long-term clinical practice the author stresses the main collisions of evidence and experience based medicine in the care of people with epilepsy. Purpose - To see, what are the professional decisions of high responsibility in the epilepsy-care, in whose the relevant clinical research is still lacking or does not give a satisfactory basis. Methods - Following the structure of the Hungarian Guideline the author points the critical situations and decisions. He explains also the causes of the dilemmas: the lack or uncertainty of evidences or the difficulty of scientific investigation of the situation. Results - There are some priorities of experience based medicine in the following areas: definition of epilepsy, classification of seizures, etiology - including genetic background -, role of precipitating and provoking factors. These are able to influence the complex diagnosis. In the pharmacotherapy the choice of the first drug and the optimal algorithm as well as the tasks during the care are also depends on personal experiences sometimes contradictory to the official recommendations. Same can occur in the choice of the non-pharmacological treatments and rehabilitation. Discussion and conclusion - Personal professional experiences (and interests of patients) must be obligatory accessories of evidence based attitude, but for achieving the optimal results, in some situations they replace the official recommendations. Therefore it is very important that the problematic patients do meet experts having necessary experiences and also professional responsibility to help in these decisions.


Assuntos
Anticonvulsivantes/administração & dosagem , Tomada de Decisões , Epilepsia/tratamento farmacológico , Medicina Baseada em Evidências , Convulsões/tratamento farmacológico , Humanos , Masculino
3.
S Afr Med J ; 110(2): 102-105, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32657678

RESUMO

The compounds present in cannabis have been in use for both recreational and medicinal purposes for many centuries. Changes in the legislation in South Africa have led to an increase in the number of people interested in using these compounds for self-medication. Many of them may approach their general practitioner as the first source of information about possible therapeutic effects. It is important that medical professionals are able to give patients the correct information. Cannabidiol (CBD) is one of the main compounds in cannabis plants, and there is evidence that it can successfully treat certain patients with epilepsy. This review looks at the most recent evidence on the use of CBD in the treatment of epilepsy and explores the mechanisms behind these beneficial effects.


Assuntos
Canabidiol/farmacologia , Cannabis/química , Epilepsia/tratamento farmacológico , Animais , Anticonvulsivantes/isolamento & purificação , Anticonvulsivantes/farmacologia , Canabidiol/isolamento & purificação , Epilepsia/fisiopatologia , Humanos , África do Sul
4.
PLoS One ; 15(7): e0235674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649723

RESUMO

BACKGROUND: Non-adherence to anti-seizure medication (ASM) therapy is an important contributing factor to the higher mortality rate and treatment failure of epilepsy. This study aimed to determine the rate and factors associated with non-adherence to ASM therapy through the WHO five dimensions of medication adherence framework. METHODS: We conducted a cross-sectional study at an outpatient Neurology Clinic of a tertiary government hospital in Malaysia. Between March and July 2019, we identified 217 patients with a confirmed diagnosis of epilepsy, receiving oral ASM therapy and able to administer their medications. We performed a semi-structured interview to gather information on sociodemographic background, clinical and medication history, and perceptions on healthcare services. Adherence to ASM therapy was evaluated using the Medication Compliance Questionnaire (MCQ). Patient's illness perception was assessed by the Brief Illness Perception Questionnaire (B-IPQ). RESULTS: 208 patients participated in this study. The median age of the study participants was 35 years (IQR 26-44). 58.2% were females and majority, 55.8%, were from the Malay ethnic group. Based on the MCQ scoring, 89 patients (42.8%) were non-adherent. Multiple logistic regression demonstrated that being employed or students (adjusted odds ratio [aOR] 2.26, 95%CI: 1.19-4.29 p = 0.012) and having an average or below average perceived access to pharmacy services (aOR 2.94, 95%CI: 1.38-6.24, p = 0.005) were significant contributors to non-adherence. CONCLUSION: Being employed or students and having an average or below average perceived access to pharmacy services were associated with ASM non-adherence Efforts to improve ASM adherence should adopt a comprehensive approach considering the success of adherence is contingent on the interrelationship of multiple dimensions.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adulto , Área Sob a Curva , Estudos Transversais , Epilepsia/diagnóstico , Epilepsia/psicologia , Feminino , Humanos , Modelos Logísticos , Malásia , Masculino , Curva ROC , Inquéritos e Questionários , Centros de Atenção Terciária
5.
Medicine (Baltimore) ; 99(22): e20507, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481472

RESUMO

RATIONALE: Asparagine synthetase deficiency (ASNSD) refers to a congenital metabolic abnormality caused by mutation in the asparagine synthetase (ASNS) gene encoded by chromosome 7q21. Herein, we report the first case of ASNSD in China, in which novel ASNS mutations were identified. PATIENT CONCERNS: A 6-month-old boy presented with a 4-month history of microcephaly and psychomotor developmental retardation and a 2-month history of epilepsy. Four months after birth, magnetic resonance imaging demonstrated a giant cyst in the right lateral ventricle, and a ventriculoperitoneal shunt was placed. Video electroencephalography showed a hypsarrhythmia pattern with a string of tonic-clonic and myoclonic seizures. On admission, physical examination showed microcephaly. Neurologic examination showed a decreased tension in the trunk muscles and an increased tension in the extremity muscles; tendon hyperreflexia was noted, and bilateral pathologic reflexes were positive. DIAGNOSIS: A diagnosed of congenital microcephaly was made. Whole-exome sequencing revealed a heterozygous deletion mutation c.666_667delCT (p.L2221Lfs*5) in exon 6 of the ASNS gene and a heterozygous missense mutation c.1424C>T (p.T457I) in exon 13 of the ASNS gene. INTERVENTIONS: After admission, intravenous adrenocorticotropic hormone and oral topiramate was administrated for 4 weeks, while the seizures persisted. Then, levetiracetam and clonazepam were added. OUTCOMES: After the follow-up period of 18 months, video electroencephalography showed that complex episodes disappeared with changes in multiple focal spike and sharp waves; 1 focal attack arising from the left occipital region and 2 focal attacks arising from the right middle temporal and the right occipital region were recorded. LESSONS: This is the first case of ASNSD in China. We identified 2 novel mutations (c.666_667delCT and c.1424C>T) in the ASNS gene, which expands the ASNS gene mutation profile and will be beneficial for genetic diagnosis.


Assuntos
Aspartato-Amônia Ligase/genética , Epilepsia/genética , Microcefalia/genética , Anticonvulsivantes/uso terapêutico , Aspartato-Amônia Ligase/deficiência , China , Clonazepam/uso terapêutico , Eletroencefalografia , Epilepsia/tratamento farmacológico , Humanos , Lactente , Levetiracetam/uso terapêutico , Masculino , Mutação de Sentido Incorreto
6.
Neurol Sci ; 41(8): 2005-2011, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32594268

RESUMO

People with epilepsy (PWE) are neither more likely to be infected by the coronavirus nor are they more likely to have severe COVID-19 manifestations because they suffer from epilepsy. However, management of COVID-19 in PWE may be more complicated than that in other individuals. Drug-drug interactions could pose significant challenges and cardiac, hepatic, or renal problems, which may happen in patients with severe COVID-19, may require adjustment to antiepileptic drugs (AEDs). In this review, we first summarize the potential drug-drug interactions between AEDs and drugs currently used in the management of COVID-19. We then summarize other challenging issues that may happen in PWE, who have COVID-19 and are receiving treatment.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Interações Medicamentosas , Epilepsia/tratamento farmacológico , Epilepsia/virologia , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Betacoronavirus , Humanos , Pandemias
7.
Clin Med (Lond) ; 20(4): e104-e106, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32518102

RESUMO

The COVID-19 pandemic will impact on how care for chronic conditions is delivered. We use epilepsy to exemplify how care for patients will be affected, and suggest ways in which healthcare systems can respond to deliver the most effective care. Where face-to-face outpatient appointments have been cancelled, telemedicine can facilitate remote clinical consultations for new and follow-up epilepsy clinic patients while reducing the risk of infection to both patients and healthcare staff. First-seizure patients will need investigation pathways rationalised, while those with chronic epilepsy will need to have reliable alternative avenues to access clinical advice. At the same time, neurologists should support emergency departments and acute medical units, advising on appropriate management of seizures and other acute neurological presentations. Ultimately, the revolution in our clinical practice is unlikely to cease after this pandemic, with reconfiguration of services likely to bring improvements in efficiency and convenience, and a reduced environmental impact.


Assuntos
Infecções por Coronavirus/complicações , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Neurologia/organização & administração , Pneumonia Viral/complicações , Telemedicina , Anticonvulsivantes/provisão & distribução , Anticonvulsivantes/uso terapêutico , Doença Crônica , Serviço Hospitalar de Emergência , Epilepsia/diagnóstico , Epilepsia/etiologia , Humanos , Pandemias , Encaminhamento e Consulta
8.
Gene ; 754: 144847, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32531456

RESUMO

BACKGROUND: A 30-year-old man presented with intellectual disability associated with epilepsy. The epilepsy was initially treated with sodium valproate and since he was 28 years-old with lamotrigine. With the addition of lamotrigine, a pattern of Brugada syndrome appeared on the electrocardiogram. The family history was positive for epilepsy from the mothers side, who had never been treated with lamotrigine. OBJECTIVE: Determine the genetic cause of the intellectual disability, epilepsy and Brugada syndrome of the patient and try to establish a possible correlation between the genetic background and the Brugada syndrome pattern under lamotrigine treatment. METHODS: A standard karyotype, array comparative genomic hybridization and two different NGS panels have done to the index case to identify the genetic causes of the intellectual disability, epilepsy and Brugada syndrome pattern. RESULTS: Genetic analyses in the family identified a de novo duplication of 1.3 Mb in 8p21.3 as well as two novel heterozygous rare variants in SCN9A and AKAP9 genes, both inherited from the mother. CONCLUSION: We hypothesize that in this family the SCN9A variant was responsible for the epileptic syndrome. In addition, given that SCN9A is lightly expressed in the heart tissue, we postulate that this SCN9A variant, alone or in combination with AKAP9 variant, might be responsible for the Brugada pattern when challenged by lamotrigine.


Assuntos
Anticonvulsivantes/efeitos adversos , Síndrome de Brugada/patologia , Epilepsia/tratamento farmacológico , Duplicação Gênica , Lamotrigina/efeitos adversos , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Adulto , Síndrome de Brugada/induzido quimicamente , Síndrome de Brugada/genética , Epilepsia/genética , Epilepsia/patologia , Humanos , Masculino
9.
Ideggyogy Sz ; 73(3-4): 121-127, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32364339

RESUMO

Background and purpose: To evaluate P-wave dispersion before and after antiepileptic drug (AED) treatment as well as to investigate the risk of ventricular repolarization using the Tpeak-Tend (Tp-e) interval and Tp-e/QT ratio in patients with epileptic disorder. Methods: A total of 63 patients receiving AED therapy and 35 healthy adults were included. ECG recordings were obtained before and 3 months after anti-epileptic treatment among patients with epilepsy. For both groups, Tp-e and Tp-e/QT ratio were measured using a 12-lead ECG device. Results: Tp-e interval, Tpe/QT and Tp-e/QTc ratios were found to be higher in the patient group than in the control group (p<0.05, for all), while QTmax ratio was significantly lower in the patient group. After 3 months of AED therapy, significant increases in QT max, QTc max, QTcd, Tp-e, Tp-e/QT, and Tp-e/QTc were found among the patients (p<0.05). When the arrhythmic effects of the drugs before and after treatment were compared, especially in the valproic acid group, there were significant increases in Tp-e interval, Tp-e/QT and Tp-e/QTc values after three months of treatment (p<0.05). Carbamazepine and levetiracetam groups were not statistically significant in terms of pre- and post-treatment values. Conclusion: It was concluded that an arrhythmogenic environment may be associated with the disease, and patients who received AED monotherapy may need to be followed up more closely for arrhythmia.


Assuntos
Anticonvulsivantes/uso terapêutico , Arritmias Cardíacas/diagnóstico , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Sistema de Condução Cardíaco/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Levetiracetam/uso terapêutico , Ácido Valproico/uso terapêutico , Adulto , Arritmias Cardíacas/fisiopatologia , Estudos de Casos e Controles , Eletrocardiografia/métodos , Sistema de Condução Cardíaco/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos
11.
Proc Natl Acad Sci U S A ; 117(19): 10155-10164, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32327603

RESUMO

Myeloperoxidase (MPO)-mediated oxidative stress has been suggested to play an important role in the pathological dysfunction of epileptic brains. However, there is currently no robust brain-imaging tool to detect real-time endogenous hypochlorite (HClO) generation by MPO or a fluorescent probe for rapid high-throughput screening of antiepileptic agents that control the MPO-mediated chlorination stress. Herein, we report an efficient two-photon fluorescence probe (named HCP) for the real-time detection of endogenous HClO signals generated by MPO in the brain of kainic acid (KA)-induced epileptic mice, where HClO-dependent chlorination of quinolone fluorophore gives the enhanced fluorescence response. With this probe, we visualized directly the endogenous HClO fluxes generated by the overexpression of MPO activity in vivo and ex vivo in mouse brains with epileptic behaviors. Notably, by using HCP, we have also constructed a high-throughput screening approach to rapidly screen the potential antiepileptic agents to control MPO-mediated oxidative stress. Moreover, from this screen, we identified that the flavonoid compound apigenin can relieve the MPO-mediated oxidative stress and inhibit the ferroptosis of neuronal cells. Overall, this work provides a versatile fluorescence tool for elucidating the role of HClO generation by MPO in the pathology of epileptic seizures and for rapidly discovering additional antiepileptic agents to prevent and treat epilepsy.


Assuntos
Apigenina/farmacologia , Encéfalo/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Ferroptose , Ácido Hipocloroso/metabolismo , Estresse Oxidativo , Peroxidase/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Mapeamento Encefálico/métodos , Epilepsia/metabolismo , Epilepsia/patologia , Corantes Fluorescentes/química , Camundongos , Neuroimagem/métodos , Fármacos Neuroprotetores/farmacologia
14.
Nurs Outlook ; 68(3): 337-344, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32334826

RESUMO

BACKGROUND: Parents across the United States use medical cannabis for their children, often without professional guidance. These parents have become more expert on medical cannabis than most health professionals. PURPOSE: Using a case-study design, this study was conducted to describe the experience of parents using medical cannabis for relief of seizures in their child or dependent. METHODS: Data were subjected to qualitative content analysis for the identification of patterns and themes. FINDINGS: Analysis of all data revealed seven themes including "Discovery of Cannabis as a Medication," "Guidance on Dosing," "Costs and Benefits of Cannabis," "Distrust of the Pharmaceutical Industry," "Federal Interference," "God and Cannabis," and "Changing Societal Perceptions about Medical Cannabis." DISCUSSION: Themes revealed a complex, multifaceted experience. Many parents report benefit from medical cannabis, and are not hindered by the financial costs or uncertainties. Political and social influences have significant impact on the stigmatization and normalization of cannabis.


Assuntos
Atitude Frente a Saúde , Epilepsia/tratamento farmacológico , Maconha Medicinal/uso terapêutico , Pais/psicologia , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Estereotipagem , Estados Unidos
15.
Artigo em Russo | MEDLINE | ID: mdl-32323939

RESUMO

OBJECTIVE: To study a cohort of adult patients with various forms of epilepsy to determine various clinical patterns of remission with subsequent relapse of seizures. MATERIALS AND METHODS: The study included 1384 patients. Two hundred and forty-nine patients with one or more remissions in the history resulted in relapse. Patients were stratified into 6 groups by clinical features of the disease. For each group, a long-term outcome of the disease was evaluated. RESULTS AND CONCLUSIONS: Return to a basic therapy after a relapse due to dose reduction or AED discontinuation does not guarantee the remission. One or more «honeymoons¼ in medical history are predictors of the low probability of achieving remission. Patients with focal epilepsies often have one or more long-term remissions that may not correspond with AED treatment. In these patients, the relapse often happen in the second decade of life with the following development of intractable epilepsy.


Assuntos
Epilepsia , Recidiva , Adulto , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Epilepsias Parciais/complicações , Epilepsias Parciais/tratamento farmacológico , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Humanos , Convulsões/complicações , Convulsões/tratamento farmacológico
16.
Medicina (B Aires) ; 80 Suppl 2: 58-62, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32150715

RESUMO

Epilepsy and attention deficit and hyperactivity disorder (ADHD) are frequent conditions in pediatrics. Their association is frequent and complex, often sharing psychiatric comorbidity. Patients who present epilepsy and ADHD, show equal frequency in both genders, with the inattentive type, as predominant presentation. Cognitive deficit increases the risk of associating ADHD in patients with epilepsy. There is not enough evidence for other risk factors, however there is enough information that allows to ant icipate its presence in some types of epilepsy, with neuropsychological models that evidence the underlying network dysfunction. The relationship with frequency and seizure control, electroencephalographic alterations and antiepileptic drugs (AEDs) is also reviewed. Recommendations to reduce adverse effects of AEDs are described. The diagnosis must therefore be based on suspicion, through clinical instruments and assessments of cognitive functioning. Multimodal treatment is also recommended in patients with ADHD with and without epilepsy. Psych stimulants can be used safely. The quality of life of the patients and their families is affected, so it is advisable for them to be supported by a specialized team that could provide education, early assessment and therapy. If they are omitted, the consequences can be negative at school, social environment and emotional development, which could be relevant and become persistent.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Epilepsia/complicações , Epilepsia/fisiopatologia , Anticonvulsivantes/uso terapêutico , Criança , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Comorbidade , Epilepsia/tratamento farmacológico , Humanos , Fatores de Risco
17.
BMC Neurol ; 20(1): 88, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164605

RESUMO

BACKGROUD: This study aimed to explore the clinical value of long - term electroencephalogram (LTM EEG) in seizure-free individuals taking antiepileptic drugs (AEDs) for more than 2 years. We try to look for clinical factors associated with epileptiform activity on LTM EEG in seizure free patients. We hope that the detection of epileptiform activity by the LTM EEG recording can develop the better treatment strategy. METHODS: The LTM EEG recordings of 770 individuals with a definite diagnosis of epilepsy were assessed. Two hundred sixty-two individuals accorded with the inclusion criteria and exclusion criteria. We collect the demographic and clinical information and LTM EEG data of these 262 individuals. We analysed the data by one-way analysis of variance and Cox proportional hazards models. RESULTS: We found that more epileptiform activity were found with LTM EEG recording than regular EEG recording in seizure-free individuals. We found several clinical factors could be associated with epileptiform activity on LTM EEG in seizure free patients by a one-way analysis: symptomatic or cryptogenic epilepsy [hazard ratio (HR) = 2.6], history of cerebral trauma (HR = 7.5), and abnormal imaging findings (HR = 3.1). The following factors suggested a correlation between history of cerebral trauma (HR = 2.4) and history of cerebral surgery (HR = 3.4) with epileptiform activity on LTM EEG presentation by multivariate logistic regression analysis. CONCLUSIONS: The study indicated a correlation of a number of factors with abnormal LTM EEG presentation: symptomatic or cryptogenic epilepsy, history of cerebral trauma, history of cerebral surgery, and abnormal imaging findings. The LTM EEG recording may help find epileptiform activity in high risk seizure-free individuals. The individuals need be reevaluated the therapeutic strateagies, and increase the hope to reach real seizure-free.


Assuntos
Anticonvulsivantes/uso terapêutico , Eletroencefalografia , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Adulto Jovem
18.
Nervenarzt ; 91(4): 353-361, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-32144451

RESUMO

In an aging society, epilepsy in old age will become a more and more relevant disease. The diagnosis is often difficult because of the frequent occurrence of focal seizures in old age, which are easily overlooked. The diagnosis is often delayed, particularly in older patients who, for example also suffer from dementia. The causes of the epilepsy can be manifold in the aging brain. Another challenge for neurologists is the medicinal treatment of geriatric epilepsy, as many anticonvulsive drugs can be associated with serious side effects and interactions. The evidence for the effectiveness and tolerability of anticonvulsive drugs in old age is insufficient, so that the choice of drugs must be made on an individual basis. Status epilepticus is a neurological emergency, which occurs not only more frequently in older than in younger persons but is also associated with a higher mortality, so that immediate diagnosis and adequate treatment is necessary.


Assuntos
Anticonvulsivantes , Epilepsia , Idoso , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Encéfalo/patologia , Demência/complicações , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Humanos
19.
PLoS One ; 15(3): e0230187, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163504

RESUMO

BACKGROUND: Epilepsy is the most common chronic neurologic disorder which affects an estimated 10.5 million children worldwide. Despite the burden, the scarcity of study held in Ethiopia. Hence, the aim of this study was to assess the treatment outcomes of epilepsy and its root causes in children with epilepsy. METHODS: A hospital-based retrospective cohort study was conducted from October 10/2017 up to October 10/2018. A total of 210 study participants who fulfilled the eligibility criteria were included in the study. A structured interviewer-administered questionnaire with a document review was used to collect data. The data were entered into Epi Info version 7.2.1 and analyzed using SPSS version 21. Descriptive statistics were computed. Simple logistic analysis was run (at 95% CI and p-value < 0.05) to identify factors associated with treatment outcome. RESULT: 210 eligible patients with epilepsy were recruited for the study. About half of the respondents were females and the majority was within the age group of 5-10 years. Phenobarbital has been the most frequently prescribed drugs and thirteen percent of patients were in the escalation phase of treatment. Eight percent of the study participants had poor adherence to the treatment regimen. About six percent of the study subjects were suffering from an uncontrolled seizure. Being a female child (AOR = 2. 21; 95%CI: 1.11, 4.41) and excellent adherence to anti-epilepsy treatment (AOR = 4. 51; 95%CI: 1.53, 13.42) were significantly associated with treatment outcome. CONCLUSION: This study revealed that many children were suffering from uncontrolled seizure and escalation therapy is being exercised. Being a female child and adherence to anti-epilepsy treatment were significantly associated with treatment outcome. Therefore, attention should be given to adherence counseling to convey a better treatment outcome.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Hospitais de Ensino , Hospitais Universitários , Humanos , Lactente , Masculino , Adesão à Medicação , Fenobarbital/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
20.
PLoS One ; 15(3): e0229953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32168507

RESUMO

Epilepsy is a complex neurological disorder characterized by sudden and recurrent seizures, which are caused by various factors, including genetic abnormalities. Several animal models of epilepsy mimic the different symptoms of this disorder. In particular, the genetic audiogenic seizure hamster from Salamanca (GASH/Sal) animals exhibit sound-induced seizures similar to the generalized tonic seizures observed in epileptic patients. However, the genetic alterations underlying the audiogenic seizure susceptibility of the GASH/Sal model remain unknown. In addition, gene variations in the GASH/Sal might have a close resemblance with those described in humans with epilepsy, which is a prerequisite for any new preclinical studies that target genetic abnormalities. Here, we performed whole exome sequencing (WES) in GASH/Sal animals and their corresponding controls to identify and characterize the mutational landscape of the GASH/Sal strain. After filtering the results, moderate- and high-impact variants were validated by Sanger sequencing, assessing the possible impact of the mutations by "in silico" reconstruction of the encoded proteins and analyzing their corresponding biological pathways. Lastly, we quantified gene expression levels by RT-qPCR. In the GASH/Sal model, WES showed the presence of 342 variations, in which 21 were classified as high-impact mutations. After a full bioinformatics analysis to highlight the high quality and reliable variants, the presence of 3 high-impact and 15 moderate-impact variants were identified. Gene expression analysis of the high-impact variants of Asb14 (ankyrin repeat and SOCS Box Containing 14), Msh3 (MutS Homolog 3) and Arhgef38 (Rho Guanine Nucleotide Exchange Factor 38) genes showed a higher expression in the GASH/Sal than in control hamsters. In silico analysis of the functional consequences indicated that those mutations in the three encoded proteins would have severe functional alterations. By functional analysis of the variants, we detected 44 significantly enriched pathways, including the glutamatergic synapse pathway. The data show three high-impact mutations with a major impact on the function of the proteins encoded by these genes, although no mutation in these three genes has been associated with some type of epilepsy until now. Furthermore, GASH/Sal animals also showed gene variants associated with different types of epilepsy that has been extensively documented, as well as mutations in other genes that encode proteins with functions related to neuronal excitability, which could be implied in the phenotype of the GASH/Sal. Our findings provide valuable genetic and biological pathway data associated to the genetic burden of the audiogenic seizure susceptibility and reinforce the need to validate the role of each key mutation in the phenotype of the GASH/Sal model.


Assuntos
Biologia Computacional , Epilepsia Reflexa/epidemiologia , Epilepsia/epidemiologia , Convulsões/epidemiologia , Estimulação Acústica , Animais , Cricetinae , Modelos Animais de Doenças , Epilepsia/tratamento farmacológico , Epilepsia/genética , Epilepsia/patologia , Epilepsia Reflexa/tratamento farmacológico , Epilepsia Reflexa/genética , Epilepsia Reflexa/patologia , Feminino , Regulação da Expressão Gênica/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Masculino , Proteína 3 Homóloga a MutS/genética , Mutação/genética , Convulsões/tratamento farmacológico , Convulsões/genética , Convulsões/patologia , Sequenciamento Completo do Exoma
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