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1.
Artigo em Inglês | MEDLINE | ID: mdl-38954792

RESUMO

Objective: To review the effects of the ketogenic diet on epilepsy in children and adolescents.Data Sources: A literature search was conducted in PubMed with no publication date or language restrictions based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. Keywords used included children, adolescent, ketogenic diet, epilepsy, and seizure.Study Selection: After excluding articles that did not meet the inclusion criteria, such as missing variables of study, adult population, and nonrandomized clinical trials, a total of 12 studies were included in the final review.Data Extraction: Data on study design, duration, sample size, population, and type of intervention were collected using a standard template.Results: The ketogenic diet and its modified versions were noted to have beneficial effects in reduction of seizure frequency and severity, with manageable adverse effects such as gastrointestinal disturbances, dehydration, dyslipidemia, hyperuricemia, infection, and metabolic acidosis.Conclusions: Depending on patient compliance and comorbidities, all variations of the ketogenic diet were found to be helpful for seizure treatment, whether as an additive or an alternative treatment option, for children and adolescents with epilepsy.Prim Care Companion CNS Disord 2024;26(3):23r03661. Author affiliations are listed at the end of this article.


Assuntos
Dieta Cetogênica , Epilepsia , Humanos , Dieta Cetogênica/efeitos adversos , Epilepsia/dietoterapia , Criança , Adolescente
2.
Arq Neuropsiquiatr ; 82(7): 1-8, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38955213

RESUMO

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with a wide clinical, cognitive, and behavioral expressivity. OBJECTIVE: To assess the neuropsychological profile of individuals clinically diagnosed with TSC and the factors that could significantly impact their cognitive development. METHODS: A total of 62 individuals with ages ranging from 3 to 38 years were followed up in a tertiary attention hospital in Southern Brazil, and they were assessed using a standard battery and the Vineland Adaptive Behavior Scales, when intellectual disability was observed. RESULTS: History of epilepsy was found in 56 participants (90.3%), and 31 (50%) presented an intellectual disability. Among the other half of TSC individuals without intellectual disability, 8 (12.9%) presented borderline classification, 20 (32.2%) presented average scores, and 3 (4.8%) were above average. In total, 17 participants (27.4%) fulfilled the diagnostic criteria for autism spectrum disorder. The results of the multiple linear regression analysis suggested that seizures, age at diagnosis, visual perception, and general attention significantly impact cognitive performance indexes. CONCLUSION: The present study suggests that the occurrence of epileptic seizures and older age at diagnosis contribute to higher impairment in the domains of cognitive development, underlining the importance of early diagnosis and the prevention of epileptic seizures or their rapid control. The development of attentional skills, visual perception, and executive functions must be followed up.


ANTECEDENTES: O complexo da esclerose tuberosa (CET) é uma doença genética autossômica dominante com ampla expressividade clínica, cognitiva e comportamental. OBJETIVO: Avaliar o perfil neuropsicológico de indivíduos com diagnóstico clínico de CET e os fatores que poderiam impactar significativamente o seu desenvolvimento cognitivo. MéTODOS: Ao todo, 62 indivíduos com idades entre 3 e 38 anos foram acompanhados em um hospital terciário do Sul do Brasil e avaliados por meio de uma bateria padrão e das Escalas de Comportamento Adaptativo Vineland, quando observada deficiência intelectual. RESULTADOS: Encontrou-se histórico de epilepsia em 56 participantes (90,3%) e de deficiência intelectual em 31 (50%). Quanto à outra metade dos indivíduos com CET sem deficiência intelectual, 8 (12,9%) apresentaram classificação limítrofe, 20 (32,2%) apresentaram pontuações médias e 3 (4,8%) estavam acima da média. No total, 17 participantes (27,4%) preenchiam os critérios diagnósticos para o transtorno do espectro autista. Os resultados da análise de regressão linear múltipla sugeriram que as crises epilépticas, a idade ao diagnóstico, a percepção visual e a atenção geral impactam significativamente os índices de desempenho cognitivo. CONCLUSãO: Este estudo sugere que a ocorrência de crises epilépticas e a maior idade ao diagnóstico contribuem para um maior comprometimento nos domínios do desenvolvimento cognitivo, e destaca-se a importância do diagnóstico precoce e da prevenção das crises epilépticas ou do seu rápido controle. O desenvolvimento de habilidades de atenção, percepção visual e funções executivas deve ser acompanhado.


Assuntos
Testes Neuropsicológicos , Esclerose Tuberosa , Humanos , Esclerose Tuberosa/complicações , Esclerose Tuberosa/psicologia , Masculino , Feminino , Criança , Adolescente , Adulto , Adulto Jovem , Brasil , Pré-Escolar , Deficiência Intelectual/etiologia , Cognição/fisiologia , Epilepsia/psicologia , Transtorno do Espectro Autista/psicologia , Estudos de Coortes , Transtornos Cognitivos/etiologia
3.
Zhonghua Er Ke Za Zhi ; 62(7): 655-660, 2024 Jul 02.
Artigo em Chinês | MEDLINE | ID: mdl-38955684

RESUMO

Objective: To investigate the risk factors of acute symptomatic seizures (ASS) and epilepsy in children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: A ambispective cohort study was used including 74 children with MOGAD who were admitted to the Department of Pediatrics of Peking University First Hospital from January 2013 to June 2023 and were followed up. Demographic information, clinical information, treatment status, ASS and epilepsy status were collected. The clinical phenotypes were classified. According to the presence or absence of ASS in the course of disease, the children and the course of disease were divided into groups with and without ASS. Chi-square test, Fisher exact test and Mann Whitney U test were used to analyze the correlation between symptoms and auxiliary examination characteristics and the occurrence of ASS in the two groups of children. Multivariate Logistic regression analysis was used for multivariate analysis. Results: The onset age of the 74 children with MOGAD was 6.58 (3.80, 9.67) years, including 38 females (51.4%) and 36 males (48.6%). The duration of the final follow-up was 2.67 (1.10, 4.12) years, with a total of 239 times acute clinical episodes. ASS occurred in 39.2% (29/74) children during the course of disease and in 29.3% (70/239) of attacks. The common phenotypes were ADEM (67 times (28.0%)), optic neuritis (37 times (15.4%)) and cerebral cortical encephalitis (31 times (13.0%)) in 239 times acute clinical episodes. The incidence of ASS in ADEM and cerebral cortical encephalitis phenotype was 28.4%(19/67) and 100.0% (31/31), respectively. Multivariate analysis showed that cortical involvement on magnetic resonance imaging during clinical attacks was an independent risk factor for ASS (ß=-1.49, OR=0.23) after excluding attacks involving only optic nerve or spinal cord (49 episodes). During the follow-up, 5 children (6.8%) had epilepsy, and all children with epilepsy had multiple clinical attacks of MOGAD and previous ASS. Conclusions: Cortical involvement on magnetic resonance imaging during clinical episodes is an independent risk factor for ASS in children with MOGAD. All MOGAD children with epilepsy had ASS and multiple MOGAD clinical episodes in the past.


Assuntos
Autoanticorpos , Epilepsia , Glicoproteína Mielina-Oligodendrócito , Convulsões , Humanos , Glicoproteína Mielina-Oligodendrócito/imunologia , Masculino , Criança , Feminino , Epilepsia/etiologia , Pré-Escolar , Fatores de Risco , Convulsões/etiologia , Autoanticorpos/sangue , Estudos de Coortes , Doença Aguda , Imageamento por Ressonância Magnética , Modelos Logísticos
4.
Nat Commun ; 15(1): 5609, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965228

RESUMO

Epilepsy affects 1% of the general population and 30% of patients are resistant to antiepileptic drugs. Although optogenetics is an efficient antiepileptic strategy, the difficulty of illuminating deep brain areas poses translational challenges. Thus, the search of alternative light sources is strongly needed. Here, we develop pH-sensitive inhibitory luminopsin (pHIL), a closed-loop chemo-optogenetic nanomachine composed of a luciferase-based light generator, a fluorescent sensor of intracellular pH (E2GFP), and an optogenetic actuator (halorhodopsin) for silencing neuronal activity. Stimulated by coelenterazine, pHIL experiences bioluminescence resonance energy transfer between luciferase and E2GFP which, under conditions of acidic pH, activates halorhodopsin. In primary neurons, pHIL senses the intracellular pH drop associated with hyperactivity and optogenetically aborts paroxysmal activity elicited by the administration of convulsants. The expression of pHIL in hippocampal pyramidal neurons is effective in decreasing duration and increasing latency of pilocarpine-induced tonic-clonic seizures upon in vivo coelenterazine administration, without affecting higher brain functions. The same treatment is effective in markedly decreasing seizure manifestations in a murine model of genetic epilepsy. The results indicate that pHIL represents a potentially promising closed-loop chemo-optogenetic strategy to treat drug-refractory epilepsy.


Assuntos
Epilepsia , Neurônios , Optogenética , Animais , Concentração de Íons de Hidrogênio , Camundongos , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Epilepsia/fisiopatologia , Epilepsia/metabolismo , Epilepsia/tratamento farmacológico , Humanos , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Convulsões/metabolismo , Halorrodopsinas/metabolismo , Halorrodopsinas/genética , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Masculino , Luciferases/metabolismo , Luciferases/genética , Células Piramidais/metabolismo , Células Piramidais/efeitos dos fármacos , Imidazóis/farmacologia , Pilocarpina/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Células HEK293 , Pirazinas
5.
Sci Rep ; 14(1): 15313, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961125

RESUMO

Epileptogenesis is the process by which a normal brain becomes hyperexcitable and capable of generating spontaneous recurrent seizures. The extensive dysregulation of gene expression associated with epileptogenesis is shaped, in part, by microRNAs (miRNAs) - short, non-coding RNAs that negatively regulate protein levels. Functional miRNA-mediated regulation can, however, be difficult to elucidate due to the complexity of miRNA-mRNA interactions. Here, we integrated miRNA and mRNA expression profiles sampled over multiple time-points during and after epileptogenesis in rats, and applied bi-clustering and Bayesian modelling to construct temporal miRNA-mRNA-mRNA interaction networks. Network analysis and enrichment of network inference with sequence- and human disease-specific information identified key regulatory miRNAs with the strongest influence on the mRNA landscape, and miRNA-mRNA interactions closely associated with epileptogenesis and subsequent epilepsy. Our findings underscore the complexity of miRNA-mRNA regulation, can be used to prioritise miRNA targets in specific systems, and offer insights into key regulatory processes in epileptogenesis with therapeutic potential for further investigation.


Assuntos
Epilepsia , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs , RNA Mensageiro , Convulsões , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Convulsões/genética , Convulsões/metabolismo , Epilepsia/genética , Epilepsia/metabolismo , Masculino , Regulação da Expressão Gênica , Teorema de Bayes , Modelos Animais de Doenças , Transcriptoma
6.
Nat Commun ; 15(1): 5528, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009561

RESUMO

The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for either epilepsy or major depressive disorder. We found that beta (12-30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward receipt, thereby predicting bias on future trials. We found reduced magnitude of bias in depressed patients, in whom the beta-specific effects were correspondingly reduced. Our findings suggest that ACC beta oscillations may orchestrate the learning of reward information to guide adaptive choice, and, more broadly, suggest a potential biomarker for anhedonia and point to future development of interventions to enhance reward impact for therapeutic benefit.


Assuntos
Transtorno Depressivo Maior , Giro do Cíngulo , Recompensa , Humanos , Giro do Cíngulo/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Masculino , Adulto , Feminino , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Comportamento de Escolha/fisiologia , Pessoa de Meia-Idade , Ritmo beta/fisiologia , Epilepsia/fisiopatologia , Adulto Jovem
7.
Clinics (Sao Paulo) ; 79: 100432, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39013275

RESUMO

OBJECTIVES: Planning for the child and adolescent to have a safe handling in the epilepsy transition process is essential. In this work, the authors translated the "Readiness Checklists" and applied them to a group of patients and their respective caregivers in the transition process to assess the possibility of using them as a monitoring and instructional instrument. METHODS: The "Readiness Checklists" were applied to thirty adolescents with epilepsy and their caregivers. The original English version of this instrument underwent a process of translation and cultural adaptation by a translator with knowledge of English and epilepsy. Subsequently, it was carried out the back-translation and the Portuguese version was compared to the original, analyzing discrepancies, thus obtaining the final version for the Brazilian population. RESULTS: Participants were able to answer the questions. In four questions there was an association between the teenagers' educational level and the response pattern to the questionnaires. The authors found a strong positive correlation between the responses of adolescents and caregivers (RhoSpearman = 0.837; p < 0.001). The application of the questionnaire by the health team was feasible for all interviewed patients and their respective caregivers. CONCLUSION: The translation and application of the "Readiness Checklists" is feasible in Portuguese. Patients with lower educational levels felt less prepared for the transition than patients with higher educational levels, independently of age. Adolescents and caregivers showed similar perceptions regarding patients' abilities. The lists can be very useful tools to assess and plan the follow-up of the population of patients with epilepsy in the process of transition.


Assuntos
Cuidadores , Lista de Checagem , Características Culturais , Epilepsia , Traduções , Humanos , Adolescente , Brasil , Feminino , Masculino , Inquéritos e Questionários , Cuidadores/psicologia , Criança , Idioma , Transição para Assistência do Adulto , Comparação Transcultural , Escolaridade , Tradução , Reprodutibilidade dos Testes
9.
Int J Mol Sci ; 25(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39000494

RESUMO

The hypothalamic-pituitary-adrenal axis is known to be involved in the pathogenesis of epilepsy and psychiatric disorders. Epileptic seizures (ESs) and psychogenic non-epileptic seizures (PNESs) are frequently differentially misdiagnosed. This study aimed to evaluate changes in serum cortisol and prolactin levels after ESs and PNESs as possible differential diagnostic biomarkers. Patients over 18 years with ESs (n = 29) and PNESs with motor manifestations (n = 45), captured on video-EEG monitoring, were included. Serum cortisol and prolactin levels as well as hemograms were assessed in blood samples taken at admission, during the first hour after the seizure, and after 6, 12, and 24 h. Cortisol and prolactine response were evident in the ES group (but not the PNES group) as an acute significant increase within the first hour after seizure. The occurrence of seizures in patients with ESs and PNESs demonstrated different circadian patterns. ROC analysis confirmed the accuracy of discrimination between paroxysmal events based on cortisol response: the AUC equals 0.865, with a prediction accuracy at the cutoff point of 376.5 nmol/L 0.811 (sensitivity 86.7%, specificity 72.4%). Thus, assessments of acute serum cortisol response to a paroxysmal event may be regarded as a simple, fast, and minimally invasive laboratory test contributing to differential diagnosis of ESs and PNESs.


Assuntos
Biomarcadores , Epilepsia , Hidrocortisona , Convulsões , Humanos , Hidrocortisona/sangue , Diagnóstico Diferencial , Biomarcadores/sangue , Masculino , Adulto , Feminino , Convulsões/sangue , Convulsões/diagnóstico , Epilepsia/sangue , Epilepsia/diagnóstico , Pessoa de Meia-Idade , Prolactina/sangue , Eletroencefalografia , Curva ROC , Adulto Jovem
10.
West Afr J Med ; 41(4): 397-405, 2024 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-39002170

RESUMO

BACKGROUND: Over the years efforts has been made through public health education to change the knowledge, attitude and practice of epilepsy and seizures among the populace in Nigeria. One surrogate method of reviewing the impact of these educational interventions includes changes in treatment-seeking behavior of People Living With Epilepsy and the reasons for their choices of treatment. METHODS: This was a cross-sectional descriptive study. Data were collected from People Living With Epilepsy attending the medical outpatient clinics in two tertiary hospitals in Enugu, Enugu State southeast Nigeria. RESULTS: A total 276 people living with epilepsy were recruited with a mean age of 30.1 years and a median age of 25 years. After the onset of epilepsy, 76(27.5%) and 70(25.4%) visited general hospitals and teaching hospitals respectively, while prayer houses and traditional healing centers were first visited by 54(19.6%) and 40(14.5%) respectively. As a second choice of care 9(3.3%) and 13(4.7%) visited prayer houses and traditional healing centers. Only 42(15.2%) selected their treatment center because they were confident of getting a cure however, this was highest for those that visited traditional healing centers 11(27.5%). The age of onset of epilepsy positively correlated with selecting orthodox treatment at the choice of care, while occupational status negatively correlated with selecting orthodox care at the same period. CONCLUSIONS: Health care seeking behaviors among PLWE in Southeast Nigeria might have changed over the years as more people living with epilepsy were more likely to select orthodox treatment compared to non-orthodox means of treatment.


CONTEXTE: Au fil des ans, des efforts ont été déployés par le biais de l'éducation en santé publique pour changer les connaissances, les attitudes et les pratiques concernant l'épilepsie et les crises d'épilepsie parmi la population au Nigeria. Une méthode indirecte pour examiner l'impact de ces interventions éducatives comprend les changements dans le comportement de recherche de traitement des personnes vivant avec l'épilepsie et les raisons de leurs choix de traitement. MÉTHODES: Il s'agit d'une étude descriptive transversale. Les données ont été collectées auprès de personnes vivant avec l'épilepsie fréquentant les cliniques de consultations externes médicales dans deux hôpitaux tertiaires à Enugu, dans l'État d'Enugu, au sud-est du Nigeria. RÉSULTATS: Au total, 276 personnes vivant avec l'épilepsie ont été recrutées, avec un âge moyen de 30,1 ans et un âge médian de 25 ans. Après le début de l'épilepsie, 76 (27,5 %) et 70 (25,4 %) ont consulté respectivement des hôpitaux généraux et des hôpitaux universitaires, tandis que les lieux de prière et les centres de guérison traditionnelle ont été les premiers consultés par respectivement 54 (19,6 %) et 40 (14,5 %). Comme deuxième choix de soins, 9 (3,3 %) et 13 (4,7 %) ont consulté des lieux de prière et des centres de guérison traditionnelle. Seuls 42 (15,2 %) ont choisi leur centre de traitement parce qu'ils étaient confiants d'obtenir une guérison, cependant, ce taux était le plus élevé pour ceux qui ont consulté les centres de guérison traditionnelle (11 soit 27,5 %). L'âge de début de l'épilepsie était positivement corrélé avec la sélection d'un traitement orthodoxe comme choix de soins, tandis que le statut professionnel était négativement corrélé avec la sélection de soins orthodoxes au même moment. CONCLUSIONS: Les comportements de recherche de soins parmi les personnes vivant avec l'épilepsie dans le sud-est du Nigeria ont peut-être changé au fil des ans, car davantage de personnes vivant avec l'épilepsie étaient plus susceptibles de choisir un traitement orthodoxe par rapport aux moyens de traitement non orthodoxes. MOTS-CLÉS: Épilepsie, Comportement de recherche de soins, Guérisseurs traditionnels, Lieux de prière, Médecine orthodoxe, sud-est du Nigeria.


Assuntos
Epilepsia , Conhecimentos, Atitudes e Prática em Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Nigéria , Epilepsia/terapia , Epilepsia/epidemiologia , Epilepsia/psicologia , Adulto , Estudos Transversais , Masculino , Feminino , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Inquéritos e Questionários
11.
Hum Brain Mapp ; 45(10): e26720, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994740

RESUMO

Electro/Magneto-EncephaloGraphy (EEG/MEG) source imaging (EMSI) of epileptic activity from deep generators is often challenging due to the higher sensitivity of EEG/MEG to superficial regions and to the spatial configuration of subcortical structures. We previously demonstrated the ability of the coherent Maximum Entropy on the Mean (cMEM) method to accurately localize the superficial cortical generators and their spatial extent. Here, we propose a depth-weighted adaptation of cMEM to localize deep generators more accurately. These methods were evaluated using realistic MEG/high-density EEG (HD-EEG) simulations of epileptic activity and actual MEG/HD-EEG recordings from patients with focal epilepsy. We incorporated depth-weighting within the MEM framework to compensate for its preference for superficial generators. We also included a mesh of both hippocampi, as an additional deep structure in the source model. We generated 5400 realistic simulations of interictal epileptic discharges for MEG and HD-EEG involving a wide range of spatial extents and signal-to-noise ratio (SNR) levels, before investigating EMSI on clinical HD-EEG in 16 patients and MEG in 14 patients. Clinical interictal epileptic discharges were marked by visual inspection. We applied three EMSI methods: cMEM, depth-weighted cMEM and depth-weighted minimum norm estimate (MNE). The ground truth was defined as the true simulated generator or as a drawn region based on clinical information available for patients. For deep sources, depth-weighted cMEM improved the localization when compared to cMEM and depth-weighted MNE, whereas depth-weighted cMEM did not deteriorate localization accuracy for superficial regions. For patients' data, we observed improvement in localization for deep sources, especially for the patients with mesial temporal epilepsy, for which cMEM failed to reconstruct the initial generator in the hippocampus. Depth weighting was more crucial for MEG (gradiometers) than for HD-EEG. Similar findings were found when considering depth weighting for the wavelet extension of MEM. In conclusion, depth-weighted cMEM improved the localization of deep sources without or with minimal deterioration of the localization of the superficial sources. This was demonstrated using extensive simulations with MEG and HD-EEG and clinical MEG and HD-EEG for epilepsy patients.


Assuntos
Eletroencefalografia , Entropia , Magnetoencefalografia , Humanos , Magnetoencefalografia/métodos , Eletroencefalografia/métodos , Adulto , Feminino , Masculino , Simulação por Computador , Adulto Jovem , Epilepsia/fisiopatologia , Epilepsia/diagnóstico por imagem , Pessoa de Meia-Idade , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Modelos Neurológicos
13.
CNS Neurosci Ther ; 30(7): e14827, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38992878

RESUMO

AIMS: This multicenter prospective cohort study (registration no. ChiCTR2000032089) aimed to investigate the relationship between saliva and plasma levetiracetam concentrations to determine whether saliva could be used for routine monitoring of levetiracetam during pregnancy. METHODS: The slot concentrations of levetiracetam in simultaneously obtained saliva and plasma samples were measured using UPLC-MS/MS. The correlations between saliva and plasma levetiracetam concentrations and the dose-normalized concentrations were compared among pregnant women in different stages and nonpregnant control participants with epilepsy. RESULTS: In total, 231 patients with 407 plasma and saliva sample pairs were enrolled from 39 centers. Linear relationships between salivary and plasma levetiracetam concentrations were reported in the enrolled population (r = 0.898, p < 0.001), including pregnant (r = 0.935, p < 0.001) and nonpregnant participants (r = 0.882, p < 0.001). Plasma concentrations were moderately higher than saliva concentrations, with ratios of saliva to plasma concentrations of 0.98 for nonpregnant women, 0.98, 1, and 1.12 for pregnant women during the first trimester, the second trimester, the and third trimester, respectively. The effective range of saliva levetiracetam concentration was found to be 9.98 µg/mL (lower limit) with an area under the curve (AUC) of 0.937 (95% confidence intervals, 0.915-0.959), sensitivity of 88.9%, specificity of 86.8%, and p < 0.001, to 24.05 µg/mL (upper limit) with an AUC of 0.952 (0.914-0.99), sensitivity of 100%, specificity of 92.3%, and p = 0.007. CONCLUSION: The saliva/plasma concentration ratio of levetiracetam remains constant during pregnancy and is similar to that in non-pregnant individuals. Monitoring levetiracetam concentration in saliva during pregnancy should be widely promoted.


Assuntos
Anticonvulsivantes , Epilepsia , Levetiracetam , Saliva , Humanos , Levetiracetam/farmacocinética , Levetiracetam/sangue , Feminino , Saliva/química , Saliva/metabolismo , Gravidez , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/sangue , Anticonvulsivantes/análise , Adulto , Epilepsia/tratamento farmacológico , Epilepsia/sangue , Adulto Jovem , Monitoramento de Medicamentos/métodos , Piracetam/análogos & derivados , Piracetam/análise , Piracetam/farmacocinética , Piracetam/sangue , Estudos Prospectivos , Estudos de Coortes , Espectrometria de Massas em Tandem/métodos
15.
Drug Res (Stuttg) ; 74(6): 296-301, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38968953

RESUMO

BACKGROUND: Epilepsy poses a significant global health challenge, particularly in regions with limited financial resources hindering access to treatment. Recent research highlights neuroinflammation, particularly involving cyclooxygenase-2 (COX-2) pathways, as a promising avenue for epilepsy management. METHODS: This study aimed to develop a Cyclooxygenase-2 inhibitor with potential anticonvulsant properties. A promising drug candidate was identified and chemically linked with phospholipids through docking analyses. The activation of this prodrug was assessed using phospholipase A2 (PLA2)-mediated hydrolysis studies. The conjugate's confirmation and cytotoxicity were evaluated using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and Sulphoramide B (SRB) assays. RESULTS: Docking studies revealed that the Celecoxib-Phospholipid conjugate exhibited a superior affinity for PLA2 compared to other drug-phospholipid conjugates. FT-IR spectroscopy confirmed the successful synthesis of the conjugate, while DSC analysis confirmed its purity and formation. PLA2-mediated hydrolysis experiments demonstrated selective activation of the prodrug depending on PLA2 concentration. SRB experiments indicated dose-dependent cytotoxic effects of Celecoxib, phospholipid non-toxicity, and efficient celecoxib-phospholipid conjugation. CONCLUSION: This study successfully developed a Celecoxib-phospholipid conjugate with potential anticonvulsant properties. The prodrug's specific activation and cytotoxicity profile makes it a promising therapeutic candidate. Further investigation into underlying mechanisms and in vivo studies is necessary to assess its translational potential fully.


Assuntos
Anticonvulsivantes , Celecoxib , Simulação de Acoplamento Molecular , Fosfolipases A2 , Fosfolipídeos , Pró-Fármacos , Celecoxib/farmacologia , Fosfolipídeos/química , Anticonvulsivantes/farmacologia , Anticonvulsivantes/síntese química , Anticonvulsivantes/química , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Pró-Fármacos/síntese química , Fosfolipases A2/metabolismo , Humanos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Animais , Varredura Diferencial de Calorimetria , Epilepsia/tratamento farmacológico , Hidrólise , Sobrevivência Celular/efeitos dos fármacos
16.
Sci Adv ; 10(28): eadk5462, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38985877

RESUMO

Adherens junction-associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses in the brain. Here, we show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs, resulting in the inability to recruit them. Ultrastructural analysis revealed significantly decreased presynaptic GBR levels in Ajap1-/- and Ajap1W183C/+ mice. Consequently, these mice exhibited reduced GBR-mediated presynaptic inhibition at excitatory and inhibitory synapses, along with impaired synaptic plasticity. Our study reveals that AJAP1 enables the postsynaptic neuron to regulate the level of presynaptic GBR-mediated inhibition, supporting the clinical relevance of loss-of-function AJAP1 variants.


Assuntos
Neurotransmissores , Sinapses , Transmissão Sináptica , Animais , Humanos , Neurotransmissores/metabolismo , Camundongos , Sinapses/metabolismo , Masculino , Alelos , Feminino , Neurônios/metabolismo , Mutação com Perda de Função , Epilepsia/metabolismo , Epilepsia/genética , Epilepsia/patologia , Camundongos Knockout , Plasticidade Neuronal , Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia
17.
Sci Rep ; 14(1): 15823, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982283

RESUMO

People with epilepsy frequently under- or inaccurately report their seizures, which poses a challenge for evaluating their treatment. The introduction of epilepsy health apps provides a novel approach that could improve seizure documentation. This study assessed the documentation performance of an app-based seizure diary and a conventional paper seizure diary. At two tertiary epilepsy centers patients were asked to use one of two offered methods to report their seizures (paper or app diary) during their stay in the epilepsy monitoring unit. The performances of both methods were assessed based on the gold standard of video-EEG annotations. In total 89 adults (54 paper and 35 app users) with focal epilepsy were included in the analysis, of which 58 (33 paper and 25 app users) experienced at least one seizure and made at least one seizure diary entry. We observed a high precision of 85.7% for the app group, whereas the paper group's precision was lower due to overreporting (66.9%). Sensitivity was similar for both methods. Our findings imply that performance of seizure self-reporting is patient-dependent but is more precise for patients who are willing to use digital apps. This may be relevant for treatment decisions and future clinical trial design.


Assuntos
Epilepsia , Aplicativos Móveis , Convulsões , Autorrelato , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Convulsões/diagnóstico , Convulsões/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Eletroencefalografia/métodos , Adulto Jovem , Idoso
18.
Int Rev Neurobiol ; 177: 135-147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39029983

RESUMO

Cannabidiol (CBD) has been investigated as a pharmacological approach for treating a myriad of neurological and psychiatric disorders, the most successful of them being its use as an antiseizure drug (ASD). Indeed, CBD has reached the clinics for the treatment of certain epileptic syndromes. This chapter aims to overview the pharmacology of CBD and its potential mechanisms of action as an ASD. First, we give an outline of the concepts, mechanisms and pharmacology pertaining to the field of study of epilepsy and epileptic seizures. In the second section, we will summarize the effects of CBD as an ASD. Next, we will discuss its potential mechanisms of action to alleviate epileptic seizures, which seem to entail multiple neurotransmitters, receptors and intracellular pathways. Finally, we will conclude and present some limitations and perspectives for future studies.


Assuntos
Anticonvulsivantes , Canabidiol , Epilepsia , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Humanos , Epilepsia/tratamento farmacológico , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Animais
20.
Ann Afr Med ; 23(2): 160-168, 2024 Apr 01.
Artigo em Francês, Inglês | MEDLINE | ID: mdl-39028164

RESUMO

OBJECTIVE: The objective of this study was to observe the effects of various clinical factors on the activation and appearance of epileptiform abnormalities (EAs) in routine electroencephalography (rEEG) by different provocation methods. METHODS: This observational study involved a review of 136 patients presented for EEG recording due to various indications and their EEG showing EAs during various provocation methods. RESULTS: Generalized spike-wave discharges (GSWDs) were the most frequent activated epileptiform pattern observed in, 81 (59.1%) recordings. This pattern was seen mainly in females 49 (P = 0.00), in patients with generalized seizures 48 (P = 0.00), in prolonged EEG records 3 (P = 0.03), and in both genetic 35 (P = 0.00) and lesional epilepsies 21 (P = 0.00). Focal sharp waves with bilateral synchrony (FSWSBS) were the most activated ictal pattern (P = 0.00). Ictal EAs after hyperventilation (HV) (P = 0.03) and intermittent photic stimulation (IPS) (P = 0.01) were mainly observed in patients with uncontrolled seizures (P = 0.00), and immune-mediated epilepsy (P = 0.02). Females sex (odds ratio [OR]: 1.33, confidence interval [CI]: 0.6-2.6; P = 0.25), bilateral tonic-clonic seizures (OR: 1.17, CI: 0.5-2.4; P = 0.31) and lesional epilepsies (OR: 1.45, CI: 0.7-2.9; P = 0.20) had risk of activation of EAs by provocation methods; however this risk was not statistically significant. While sleep deprivation (SD) (OR: 6.33, CI: 2.2-18.2; P = 0.00), nonrapid eye movement sleep (NREM) (OR: 2.41, CI: 1.0-5.4; P = 0.00), and prolong EEG recording (OR: 1.91, CI: 0.9-3.9; P = 0.04) were leading to a statistically significant risk of activation and appearances of EAs due to provocation. CONCLUSION: Different provocation methods can activate and augment the variety of EEG patterns of diverse clinical significance. Detection of activated ictal EAs is dependent on various patient factors, including seizure control, and the provocation method applied. Further larger prospective cohort studies with adequate sample sizes are warranted.


Résumé Objectif:L'objectif de cette étude était d'observer les effets de différents facteurs cliniques sur l'activation et l'apparition d'épileptiformes. anomalies (EA) dans l'électroencéphalographie (EEG) de routine par différentes méthodes de provocation.Méthodes:Cette étude observationnelle impliquait une examen de 136 patients présentés pour un enregistrement EEG en raison de diverses indications et de leurs EEG montrant des EA au cours de diverses méthodes de provocation.Résultats:Les décharges épileptiformes généralisées étaient le schéma épileptiforme activé le plus fréquemment observé dans 81 enregistrements (59,1 %). Cele schéma a été observé principalement chez les femmes 49 (P = 0,00), chez les patients présentant des crises généralisées 48 (P = 0,00), dans les enregistrements EEG prolongés 3 (P = 0,03), et dans les épilepsies génétiques 35 (P = 0,00) et lésionnelles 21 (P = 0,00). Les ondes aiguës focales avec synchronie bilatérale étaient les ondes critiques les plus activées motif (P = 0,00). Les AE ictales après hyperventilation (P = 0,03) et stimulation photique intermittente (P = 0,01) ont été principalement observées chez les patients avec crises incontrôlées (P = 0,00) et épilepsie à médiation immunitaire (P = 0,02). Sexe féminin (oddsratio [OR] : 1,33, intervalle de confiance [IC] :0,6­2,6; P = 0,25), crises tonico-cloniques bilatérales (OR : 1,17, IC : 0,5­2,4; P = 0,31) et épilepsies lésionnelles (OR : 1,45, IC : 0,7­2,9; P = 0,20) avait un risque d'activation des EA par des méthodes de provocation; cependant, ce risque n'était pas statistiquement significatif. Alors que la privation de sommeil (OR : 6,33, IC : 2,2­18,2; P = 0,00), sommeil à mouvements oculaires non rapides (OR : 2,41, IC : 1,0­5,4; P = 0,00) et prolonger l'enregistrement EEG (OR : 1,91, IC : 0,9­3,9; P = 0,04) entraînaient un risque statistiquement significatif d'activation et d'apparition d'AE par provocation.Conclusion:Différent les méthodes de provocation peuvent activer et augmenter la variété des schémas EEG de signification clinique diverse. La détection des EA ictaux activés est dépend de divers facteurs liés au patient, y compris le contrôle des crises et la méthode de provocation appliquée. D'autres études de cohorte prospectives plus importantes avec des tailles d'échantillons adéquates sont justifiées.


Assuntos
Eletroencefalografia , Epilepsia , Convulsões , Humanos , Feminino , Eletroencefalografia/métodos , Masculino , Adulto , Epilepsia/fisiopatologia , Epilepsia/diagnóstico , Pessoa de Meia-Idade , Adolescente , Convulsões/diagnóstico , Convulsões/fisiopatologia , Adulto Jovem , Criança , Estimulação Luminosa/métodos , Hiperventilação/fisiopatologia , Pré-Escolar , Estudos Retrospectivos , Idoso
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