Long­term effects of vitexin against development of pentylenetetrazole­induced kindling in rats.

Evidence is provided that the glycosylated flavonoid vitexin (apigenin­8­C­beta­D­glucopyranoside) attenuates pentylenetetrazole (PTZ)­induced acute tonic­clonic seizures in rats. However, the effects of chronic and systemic vitexin in PTZ­kindled rats remain unknown. The aim of this work was to investigate the effect of long­term treatment with vitexin in the PTZ­kindling model of epilepsy. Male Wistar rats received intraperitoneal injections of PTZ at a subconvulsive dose of 35 mg/kg every other day for 29 days. Either saline containing dimethyl sulfoxide - DMSO 1%  (vehicle), diazepam (2 mg/kg; positive control) or vitexin (2.5 mg/kg) was administered intraperitoneally 30 min before each PTZ injection. The behavioral reactions were recorded by 30 min immediately after each PTZ injection. Furthermore, on the 31st day, that is, 48 h after the latter dose of PTZ, the animals were euthanized and renal and hepatic biochemical markers were evaluated in blood serum. Chronic treatment with either diazepam or vitexin attenuated the seizures provoked by PTZ injections. Neither diazepam nor vitexin caused changes in renal levels of creatinine and urea and in hepatic levels of aspartate aminotransferase and alanine aminotransferase. Our findings suggest that chronic administration of vitexin attenuates the progression of PTZ­induced kindling without causing side effects on kidneys and liver.

Smartphone applications for the management of epilepsy in children and adolescents.

OBJECTIVE: To describe how smartphone applications can contribute to the management of epilepsy in children and adolescents. DATA SOURCE: This is an integrative review conducted on the Medline, PubMed, and SciELO databases, based on the descriptors "epilepsy" and "smartphone." Original studies published between 2017-2023 in Portuguese or English that addressed the research question were included. Theses and dissertations, duplicate studies, literature reviews, and studies that did not answer the research question were excluded. DATA SYNTHESIS: A total of 178 studies were located, of which six were selected for this review. The sample included 731 participants (631 children and adolescents with epilepsy and 100 caregivers). The applications allow for the collection of seizure frequency; timing and type of crisis; reminders for medication administration; and information about sleep quality. They can store these data for healthcare professionals, caregivers, and users to monitor the progress of the condition. CONCLUSIONS: The use of applications in managing seizures in children and adolescents with epilepsy shows promising results by promoting continuous and personalized monitoring. Further studies are needed to optimize beneficial outcomes and overcome challenges.

Neurological outcomes in neonates treated with therapeutic hypothermia: challenges in a developing country.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) affects 1.5 newborns per 1 thousand term live births. Therapeutic hypothermia (TH) does not prevent all adverse outcomes. The experience with TH is still limited in Latin America. In Rio de Janeiro, Hospital Universitário Pedro Ernesto treats neonates with HIE since 2017 using the servo-controlled system. OBJECTIVE: To describe the frequency of epilepsy, altered neurological exam, and neurodevelopmental delay at 12 months of age in patients treated with TH in a reference hospital in Rio de Janeiro and to evaluate the possible risk associations with clinical data and data from complementary exams. METHODS: We evaluated medical records from the Neonatal Intensive Care Unit hospitalization and from first evaluation recorded at 12 months of age in the High-Risk Neonate Follow-up Outpatient Sevice. RESULTS: A total of 30 subjects were included in the study. We found epilepsy in 18.2% of the patients, altered neurological exam in 40.9%, and neurodevelopmental delay in 36.4%. We also found a significant relationship between altered magnetic resonance imaging scan and subsequent altered neurological exam. Our findings are in line with those of the international literature, which shows that adverse outcomes are still observed, even when TH is applied. Brazilian data shows our limited access to complementary exams. The rate of loss to follow-up was of 26.6%, probably due to the coronavirus disease 2019 (COVID-19) pandemic and to unfavorable socioeconomic conditions. More time for prospective follow-up and protocol adjustments should contribute to improve our data. CONCLUSION: High incidences of epilepsy, altered neurological exams, and neurodevelopmental delay were found, despite the use of TH. A more efficient use of resources is needed, as well as measures such as early intervention.

ANTECEDENTES: A encefalopatia hipóxico-isquêmica (EHI) afeta 1,5 a cada mil nascidos vivos a termo. A hipotermia terapêutica (HT) não previne todos os desfechos negativos. A experiência com HT ainda é limitada na América Latina. No Rio de Janeiro, o Hospital Universitário Pedro Ernesto trata neonatos com EHI desde 2017 usando o sistema servo-controlado. OBJETIVO: Relatar a frequência de epilepsia, de alteração em exame neurológico e de atraso no desenvolvimento neuropsicomotor aos 12 meses de idade nos pacientes submetidos a HT em um hospital de referência no estado do Rio de Janeiro e avaliar as associações de risco com dados clínicos e de exames complementares. MéTODOS: Foi feita análise de dados do prontuário médico da internação na UTI Neonatal e da primeira avaliação registrada a partir de 12 meses completos de idade no Ambulatório de Seguimento de Recém-Nascido de Alto Risco. RESULTADOS: Ao todo, 30 pacientes foram incluídos. As frequências de epilepsia, de alteração em exame neurológico e de atraso no desenvolvimento neuropsicomotor aos 12 meses de idade foram, respectivamente, de 18,2%, 40,9% e 36,4%. Observamos relação significativa entre alteração na ressonância magnética e posterior alteração no exame neurológico. Nossos achados corroboram a literatura internacional, em que desfechos desfavoráveis ocorrem mesmo aplicando-se HT. Dados brasileiros mostram a limitação da disponibilidade dos exames complementares. Houve perda de seguimento de 26,6%, provavelmente pela pandemia da doença do coronavírus 2019 (coronavirus disease 2019, COVID-19, em inglês) e condições socioeconômicas desfavoráveis. Mais tempo de seguimento e ajustes no protocolo devem contribuir para melhorar nossos dados. CONCLUSãO: Foram encontradas elevadas incidências de epilepsia, de exame neurológico alterado e de atraso no neurodesenvolvimento, apesar da HT. Faz-se necessário uso mais eficiente dos recursos disponíveis, bem como de medidas como intervenção precoce.

Modification of pre-ictal cortico-hippocampal oscillations by medial ganglionic eminence precursor cells grafting in the pilocarpine model of epilepsy.

Cell replacement therapies using medial ganglionic eminence (MGE)-derived GABAergic precursors reduce seizures by restoring inhibition in animal models of epilepsy. However, how MGE-derived cells affect abnormal neuronal networks and consequently brain oscillations to reduce ictogenesis is still under investigation. We performed quantitative analysis of pre-ictal local field potentials (LFP) of cortical and hippocampal CA1 areas recorded in vivo in the pilocarpine rat model of epilepsy, with or without intrahippocampal MGE-precursor grafts (PILO and PILO+MGE groups, respectively). The PILO+MGE animals had a significant reduction in the number of seizures. The quantitative analysis of pre-ictal LFP showed decreased power of cortical and hippocampal delta, theta and beta oscillations from the 5 min. interictal baseline to the 20 s. pre-ictal period in both groups. However, PILO+MGE animals had higher power of slow and fast oscillations in the cortex and lower power of slow and fast oscillations in the hippocampus compared to the PILO group. Additionally, PILO+MGE animals exhibited decreased cortico-hippocampal synchrony for theta and gamma oscillations at seizure onset and lower hippocampal CA1 synchrony between delta and theta with slow gamma oscillations compared to PILO animals. These findings suggest that MGE-derived cell integration into the abnormally rewired network may help control ictogenesis.

[Contribution of the Ibero-American Academy of Neuropediatrics to the knowledge of self-limited epilepsy in infants]. / Aporte de la Academia Iberoamericana de Neuropediatría al conocimiento de la epilepsia autolimitada del lactante.

Since the first presentation at the IV Iberoamerican Academy of Neuropediatrics Congress in 1995, our group has studied self-limited infantile epilepsy (SeLIE), both familial and non-familial, corroborating that they belong to the same entity due to their clinical and electroencephalographic characteristics and excellent prognosis. Associations were found with paroxysmal dyskinesias and migraine, as well as with hemiplegic migraine, episodic ataxia and intellectual disability in atypical cases. Mutations in PRRT2 are the main cause of SeLIE, however, other genes, such as SCN2A, KCNQ2-3 and SCN8A, have been recognized. Drugs for focal seizures that act on sodium channels are indicated. In emergencies, during cluster seizures, the use of benzodiazepines is important. In this publication, we review our contribution in SeLIE from our first report to the present and review the existing literature on the subject.

Desde la primera presentación en el IV Congreso de la Academia Iberoamericana de Neurología Pediátrica en 1995, nuestro grupo ha estudiado las epilepsias autolimitadas del lactante (EAL), tanto familiares y no familiares, corroborando que pertenecen a una misma entidad por sus características clínicas, electroencefalográficas y excelente pronóstico. Se encontraron asociaciones con discinesias paroxísticas y migraña, como también con la migraña hemipléjica, la ataxia episódica y la discapacidad intelectual en casos atípicas. Las mutaciones en PRRT2 son la principal causa de EAL. Sin embargo, otros genes, como SCN2A, KCNQ2-3 y SCN8A, han sido reconocidos. Los fármacos para las crisis focales que actúan sobre los canales de sodio son los indicados. En emergencias, durante las convulsiones agrupadas, es importante el uso de benzodiacepinas. En esta publicación, hacemos un recorrido de nuestro aporte en EAL desde nuestra primera contribución hasta la actualidad y además realizamos una revisión de la literatura existente sobre el tema.

[Epilepsy or functional neurological disorder. Diagnostic strategies]. / Epilepsia o trastorno neurológico funcional. Estrategias para el diagnóstico.

A seizure is the manifestation of symptoms or signs produced by excessive or synchronous neuronal activity in the brain. It usually presents as brief, self-limited episodes of involuntary movements that can affect a part or the entire body and that are sometimes accompanied by loss of consciousness and sphincter control. Epilepsy may be considered after a single unprovoked seizure in a patient with a high risk of recurrence. Paroxysmal non-epileptic disorders are defined as episodes of sudden onset and short duration that imitate an epileptic seizure, caused by a brain dysfunction of diverse origin that, unlike epilepsy, is not due to excessive neuronal discharge. Its incidence is much higher than epilepsy and it can appear at any age. It is important for diagnosis to analyze the triggering factors, the details of each episode, physical examination and only proceed to basic complementary tests such as video-electroencephalogram in case of doubt or for diagnostic confirmation. There is a tendency to overdiagnose epilepsy and excessive use of anticonvulsant drugs. Those that can most frequently be confused are syncope, "daydreams" and pseudoseizures.

Una convulsión es la manifestación de signos o síntomas producidos por una actividad neuronal excesiva o sincrónica en el cerebro. Suele presentarse como episodios breves, autolimitados, de movimientos involuntarios que pueden afectar a una parte del cuerpo o su totalidad y que, en ocasiones, se acompañan de pérdida de la conciencia y control de esfínteres. Puede considerarse epilepsia una sola crisis no provocada en un paciente con un elevado riesgo de recurrencia. Los trastornos paroxísticos no epilépticos se definen como episodios de aparición brusca y de breve duración que imitan a una crisis epiléptica, originados por una disfunción cerebral de origen diverso que a diferencia de la epilepsia no obedecen a una descarga neuronal excesiva. Su incidencia es mucho más elevada que la epilepsia y pueden aparecer a cualquier edad. Es importante para el diagnóstico analizar los factores desencadenantes, los pormenores de cada episodio, examen físico y solamente proceder a los exámenes complementarios básicos como video-electroencefalograma en caso de duda o para confirmación diagnóstica. Existe la tendencia a sobrediagnosticar epilepsia y al uso excesivo de fármacos anticonvulsivos. Los que con mayor frecuencia se pueden confundir son los síncopes, ensoñaciones y las pseudocrisis.

[Epileptic syndromes in pediatrics. What's new?] / Síndromes epilépticos en pediatría ¿Qué hay de nuevo?

The classification of epilepsy syndromes in pediatrics has undergone significant changes. In 2017, the International League Against Epilepsy Task Force on Nosology and Definitions proposed a new classification and definition and established mandatory, exclusionary, and alert criteria for the diagnosis of the different syndromes. The goal of this article is not to provide an extensive review of each syndrome, but to focus on syndromes that suffered important changes in terminology and/or when consensus or new methods to improve diagnosis and treatment have been designed.

La clasificación de síndromes epilépticos en pediatría ha sufrido cambios significativos. En el 2017, la Comisión en Nosología y Definiciones de la Liga Internacional Contra La Epilepsia propuso una nueva clasificación y definición y estableció criterios, mandatarios, de exclusión y de alerta para los diferentes síndromes. El objetivo de este artículo no es revisar detalladamente cada uno de estos síndromes, pero enfatizar en los que han sufrido cambios importantes en terminología o en los cuales se ha obtenido consenso o se han diseñado nuevos métodos para optimizar el diagnóstico y tratamiento.

Conjunto de herramientas del promotor para que la epilepsia sea una prioridad en la Región de las Américas

La Caja de herramientas del promotor para que la epilepsia sea una prioridad en región de las Américas fue desarrollada para ayudar a individuos y organizaciones a identificar oportunidades que permitan la plena participación de las personas con epilepsia en la comunidad. Fue desarrollado para las organizaciones que buscan orientación, ideas o inspiración a medida que desarrollan proyectos de promoción de la epilepsia. La caja de herramientas está dirigida a las organizaciones de la sociedad civil que trabajan en toda la Región de las Américas y ha sido inspirada por las necesidades y experiencias de las personas con epilepsia. Los diversos módulos y temas abordados pueden ser utilizados como una guía paso a paso para orientar en el proceso de planificación de la incidencia, o como una referencia independiente o un conjunto de recursos que pueden ser utilizados cuando se encuentra un problema u oportunidad en el contexto de la política existente sobre epilepsia, la legislación o el acceso a la atención. No pretende ser una guía independiente sobre cómo llevar a cabo la promoción. En su lugar, proporciona pistas clave para la reflexión y el debate, indicaciones básicas para la incidencia (la teoría) y herramientas esenciales para ayudar a la sociedad civil a trabajar de forma lógica a través de las distintas etapas de un ciclo de planificación de la incidencia. Pretende ser versátil y útil para diversos públicos. Ha sido desarrollado conjuntamente por la Organización Panamericana de la Salud y la Oficina Internacional para la Epilepsia (IBE en inglés) con aportaciones de partes interesadas clave, incluidas personas con epilepsia y sus familias, y con proveedores de atención sanitaria de la Región. A través de una evaluación inicial de las necesidades, las partes interesadas aportaron sus puntos de vista sobre los recursos de los que disponían actualmente, las mejores prácticas que querían compartir, las áreas en las que buscaban apoyo y las oportunidades de apoyo o colaboración adicionales.

Advocate’s toolkit for making epilepsy a priority in the Americas

The Advocate’s Toolkit for Making Epilepsy a Priority in the Americas was developed to help individuals and organizations to identify opportunities that provides full participation of people with epilepsy in the community. It was developed for organizations looking for guidance, ideas, or inspiration as they develop advocacy projects around epilepsy. The toolkit is aimed at civil society organizations working across the Region of the Americas and has been heavily influenced by the needs and experiences of people with epilepsy. The various modules and topics addressed in this toolkit can be used both as a step-by-step guide to lead in the advocacy planning process, or as a reference or set of stand-alone resources that can be used when encountering a problem or opportunity in the context of existing epilepsy policy, legislation, or access to care. It is not meant as a stand-alone guide on how to conduct advocacy activities. Instead, it provides key prompts for reflection and discussion, basic advocacy pointers (the theory), and essential tools to help civil society to work logically through the various stages of an advocacy planning cycle. It is meant to be versatile and useful to a variety of audiences. It recognises that stigma is a major barrier preventing social inclusion and access to health care and treatment for people with epilepsy. Civil society can use the guidance, evidence, and templates to promote epilepsy as a public health priority in their local community or at the national, and regional levels. The toolkit was co-developed by the Pan American Health Organization and the International Bureau for Epilepsy (IBE) with important input from key stakeholders, including persons with epilepsy and their families, and with healthcare providers from the Region. It includes input from others with a connection to epilepsy either personally or through an organization. Through an initial needs assessment, stakeholders provided their perspectives on resources that were currently available to them, best practices they wanted to share, areas where they were seeking support, and opportunities for additional support or collaboration. This toolkit was developed based on that input as well as on feedback on initial drafts. The toolkit can be used as a companion document to support implementation of the WHO Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders (IGAP) which recognises that epilepsy is treatable, medication can be made affordable and basic epilepsy care can be provided at the primary care level for all people. All countries across the Americas have ratified IGAP and the UN SDG’s and can use this toolkit to plan their advocacy. The toolkit is full of resources, ideas, and guidance for addressing and dismantling stigma and for monitoring and evaluating progress towards implementation of the IGAP.

[Etiology of epilepsy in Mexico: results from the national multi-centre register]. / Etiología de la epilepsia en México: resultados del registro multicéntrico nacional.

INTRODUCTION: Epilepsy affects millions of people and its geographical patterns are usually linked to etiological aspects. Our objective was to describe main etiologies of epilepsy in Mexico. PATIENTS AND METHODS: We selected patients from the Multicenter Epilepsy Registry carried out from 2021 to 2022 in 89 Mexican hospitals in 31 states, a sample predominantly of pediatric age. Only patients with electroencephalography and neuroimaging studies were included. RESULTS: We analyzed 6,653 patients with documented etiologies. Etiology frequency with confidence interval (95% CI) was: structural 46.1% (44.9-47.3), genetic 12.9% (12.1-13.7), infectious 2.9%. (2.5-3.3), metabolic 1.4% (1.1-1.7), immune 0.9% (0.8-1.3) and unknown 40.9% (39.8-42.2). The two main structural etiologies were malformations of cortical development and hypoxic-ischemic encephalopathy. Neurocysticercosis represented a minority with only 1%. Structural and genetic etiologies were associated with focal and generalized onset seizures respectively. Status epilepticus was identified, mostly with motor component, associated with immune and infectious etiologies. Comorbidities were found in 61.6%, mainly neurological development disorders. Drug-resistant epilepsy was more common in patients with immune, infectious and structural etiologies. CONCLUSIONS: The main etiology of epilepsy was structural. The frequency of genetic etiology was relatively lower than in other series, possibly due to the limited availability of genetic tests. Despite technological advances, a large fraction of epilepsies still has unknown origin.

TITLE: Etiología de la epilepsia en México: resultados del registro multicéntrico nacional.Introducción. La epilepsia afecta a millones de personas y sus patrones geográficos suelen estar vinculados a aspectos etiológicos. Nuestro objetivo fue describir las principales etiologías de epilepsia en México. Pacientes y métodos. Seleccionamos a pacientes del Registro Multicéntrico de Epilepsia realizado de 2021 a 2022 en 89 hospitales mexicanos de 31 estados, una muestra con predominio en edad pediátrica. Se incluyó a pacientes con estudios de electroencefalografía y neuroimagen. Resultados. Analizamos a 6.653 pacientes con etiologías documentadas. Las frecuencias de etiologías con intervalo de confianza al 95% fueron: estructural, 46,1% (44,9-47,3); genética, 12,9% (12,1-13,7); infecciosa, 2,9% (2,5-3,3); metabólica, 1,4% (1,1-1,7); inmunitaria, 0,9% (0,8-1,3); y desconocida, 40,9% (39,8-42,2). Las dos principales etiologías estructurales fueron las malformaciones del desarrollo cortical y la encefalopatía hipóxico-isquémica. La neurocisticercosis representó una minoría, con sólo el 1%. Las etiologías estructurales y genéticas se relacionaron con crisis de inicio focal y generalizado, respectivamente. Se identificó estado epiléptico, en su mayoría con componente motor, asociado a etiologías inmunitarias e infecciosas. Se encontraron comorbilidades en el 61,6%, principalmente trastornos del desarrollo neurológico. La epilepsia farmacorresistente fue más frecuente en pacientes con etiologías inmunitaria, infecciosa y estructural. Conclusiones. La principal etiología de la epilepsia fue estructural. La frecuencia de etiología genética fue menor que en otras series por la limitada disponibilidad de pruebas genéticas. A pesar de los avances tecnológicos, una gran parte de las epilepsias aún tiene un origen desconocido.

Teratogenicity of Valproic Acid: Can Reverse its Possible Effects on Testicular Development with Vitamin E? / Teratogenicidad del Ácido Valproico: ¿Se Pueden Revertir sus Posibles Efectos sobre el Desarrollo Testicular con la Vitamina E?

Epilepsy is the chronic non-communicable disease of the nervous system most prevalent in the world. Valproic acid (VPA) is one of the most used drugs in the treatment of epilepsy but with various side effects. One of the organs that can be affected is the testis, where it has been seen that men treated with VPA reduce their fertility rates, in addition to causing endocrine disorders by decreasing androgens and gonadotropins. In animal models, it has been shown to reduce the weights of the glands attached to the male reproductive tract, as well as at the testicular level, decreasing sperm concentration and increasing apoptotic cell count. These effects are because VPA increases reactive oxygen species (ROS), causing damage to macromolecules and affecting all cellular processes sensitive to oxide reduction. Throughout testicular development, in utero, it has been seen that the expression of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase, are lower during early embryonic development, as well as vitamin E (VE) is decreased. Therefore, they are not sufficient to reverse the toxic effects of ROS. The objective of this study was to review the use of VPA during pregnancy, its effect on testicular development, and to explore the potential protective role of vitamin E.

La epilepsia es una enfermedad crónica no transmisible que afecta al sistema nervioso más prevalente en el mundo. Dentro de los tratamientos, uno de los fármacos más utilizados es el ácido valproico (AVP), el que ocasiona diversos efectos secundarios. Entre los órganos que se pueden ver afectados se encuentra la gónada masculina, en donde se ha visto que hombres en tratamiento con AVP reducen sus tasas de fecundidad, además de causar trastornos endocrinos disminuyendo andrógenos y gonadotrofinas. En modelos animales, se ha visto que disminuye los pesos de las glándulas anexas al tracto reproductor masculino, como también a nivel testicular, disminuyendo la concentración espermática y aumentando el recuento de células apoptóticas. Estos efectos se deberían a que el AVP aumenta las especies reactivas de oxígeno (ROS), ocasionando daño en macromoléculas, afectando todos los procesos celulares sensibles a óxido reducción. A lo largo del desarrollo testicular, in utero se ha visto que la expresión de enzimas antioxidantes como superóxido dismutasa, catalasa y glutatión peroxidasa, son más bajos durante el desarrollo embrionario temprano, como también la vitamina E (VE) se encuentra disminuida. Por tanto, no resultan suficientes para revertir los efectos tóxicos de las ROS. El objetivo de esta revisión fue asociar el uso de AVP durante la gestación y sus efectos a nivel del desarrollo testicular y describir el potencial rol protector de la VE.

Use of artisanal and non-regulated cannabis-based products for the treatment of epilepsy in a low-income population.

INTRODUCTION: Several artisanal and non-regulated cannabis-based products used for the treatment of epilepsy are available and can be easily obtained. Many of these preparations lack proper quality validation and exhibit cannabinoid contents significantly different from those stated on their labels, along with the presence of potentially harmful compounds. This study aims to evaluate the frequency of use and prescription patterns of these products among patients with epilepsy from a low-income population. METHODS: Observational and cross-sectional study. A survey was conducted on patients with epilepsy at a public hospital in Bogotá, Colombia. RESULTS: A total of 380 patients were evaluated, with 10.3 % (n = 39) reporting the use of artisanal and non-regulated cannabis-based products for the treatment of epilepsy. Among these patients, 84.6 % (n = 33) used the product on their own initiative, without a medical recommendation. Only 7.7 % (n = 3) of the patients had a record of the consumption of these products in their medical history. Age (p = 0.002), type of therapeutic response (p = 0.01), number of previous antiseizure medications used (p < 0.01), and non-pharmacological treatment such as vagal nerve stimulation (p < 0.01) showed a statistically significant association with the utilization of these products. CONCLUSION: One in ten patients with epilepsy has used artisanal and non-regulated cannabis-based products for the treatment of their condition. The majority of patients used these products on their own initiative, without a medical recommendation. The prevalence of consuming these products was higher among younger individuals with uncontrolled epilepsy, who had previously used multiple antiseizure medications and other non-pharmacological alternatives such as vagal nerve stimulation.

Exercise-produced irisin effects on brain-related pathological conditions.

Exercise increases peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) expression, which in turn causes the fibronectin type III domain containing 5 (FNDC5) protein to be produced. This protein is then cleaved, primarily in skeletal muscle fibers, to produce irisin. When the mature FNDC5 is cleaved by proteases, Irisin - which is the fibronectin III domain without the signal sequence - is released. Resistance, aerobic, and high-intensity interval training (HIIT) are recognized as forms of physical exercise that raise irisin levels, and insulin receptor phosphorylation in tyrosine residues, favoring an increase in the activity of the insulin-dependent pathway (PI3K pathway) and assisting in the fight against insulin resistance, inflammation, and cognitive decline. Irisin may represent a promising option for the therapeutic targeting in several brain-related pathological conditions, like Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, type 2 diabetes, and obesity. Exercise protocols are healthy and inexpensive interventions that can help find cellular and molecular changes in several brain-related pathological conditions. Here, it was reviewed what is known about exercise-produced irisin studies involving AD, PD, epilepsy, type 2 diabetes, and obesity.

Pentylenetetrazole: A review.

Pentylenetetrazole (PTZ), a tetrazole derivative, is commonly used as a chemical agent to induce neurological disorders and replicate the characteristics of human epileptic seizures in animal models. This review offers a comprehensive analysis of the behavioral, neurophysiological, and neurochemical changes induced by PTZ. The epileptogenic and neurotoxic mechanisms of PTZ are associated with an imbalance between the GABAergic and glutamatergic systems. At doses exceeding 60 mg/kg, PTZ exerts its epileptic effects by non-competitively antagonizing GABAA receptors and activating NMDA receptors, resulting in an increased influx of cations such as Na+ and Ca2+. Additionally, PTZ promotes oxidative stress, microglial activation, and the synthesis of pro-inflammatory mediators, all of which are features characteristic of glutamatergic excitotoxicity. These mechanisms ultimately lead to epileptic seizures and neuronal cell death, which depend on the dosage and method of administration. The behavioral, electroencephalographic, and histological changes associated with PTZ further establish it as a valuable preclinical model for the study of epileptic seizures, owing to its simplicity, cost-effectiveness, and reproducibility.

Perfil de prescripción de levetiracetam en niños menores de cuatro años atendidos en un hospital de alta complejidad de Chile / Levetiracetam prescription profile in children younger than 4 years treated at a tertiary care hospital in Chile

Introducción. El levetiracetam (LEV) es un antiepiléptico aprobado por el Instituto de Salud Pública de Chile como terapia concomitante en crisis epilépticas en niños mayores de cuatro años. Sin embargo, es ampliamente indicado desde el periodo neonatal, lo que hace necesario evaluar su utilización fuera de ficha técnica. Objetivo. Determinar el perfil de prescripción-indicación de LEV en el tratamiento de las crisis epilépticas en menores de cuatro años en un hospital de alta complejidad del sur de Chile. Población y método. Estudio observacional, descriptivo y retrospectivo. Se revisaron las historias clínicas de quienes iniciaron tratamiento con LEV entre 2014 y 2019, y se recopilaron datos sobre variables sociodemográficas, farmacológicas y clínicas. El análisis se basó en la descripción del perfil de los pacientes, prescripción, seguimiento y seguridad. Resultados. Se incluyeron 68 pacientes: 40 (58,8 %) de sexo masculino, 49 (72,1 %) con edad gestacional ≥ 37 semanas. La etiología principal de la epilepsia fue de tipo estructural (35,3 %); el LEV se utilizó principalmente en niños diagnosticados con malformación del sistema nervioso central (17,6 %) y predominó la monoterapia (55,9 %). En el 50 % se usó LEV para crisis focales. Cinco niños (7,3 %) presentaron trastornos de tipo psiquiátrico clasificados como probables reacciones adversas al medicamento. Conclusión. El LEV se utilizó en niños con diferentes diagnósticos con baja frecuencia de eventos adversos. El perfil de utilización varió en los diferentes grupos etarios. Es necesario identificar en futuros estudios la efectividad especialmente en el recién nacido y en epilepsias refractarias.

Introduction. Levetiracetam (LEV) is an antiepileptic drug approved by the Chilean Institute of Public Health as concomitant therapy for epileptic seizures in children older than 4 years of age. However, it is widely prescribed from the neonatal period, which makes it necessary to evaluate its off-label use. Objective. To determine the prescription-indication profile of LEV in the treatment of epileptic seizures in children younger than 4 years in a tertiary care hospital in southern Chile. Population and method. Observational, descriptive, and retrospective study. The medical records of patients who started treatment with LEV between 2014 and 2019 were reviewed, and data on sociodemographic, pharmacological, and clinical variables were collected. The analysis was based on the description of the profile of patients, prescriptions, follow-up, and safety. Results. A total of 68 patients were included: 40 (58.8%) were males, 49 (72.1%) were born at a gestational age ≥ 37 weeks. The main etiology of epilepsy was structural (35.3%); LEV was mostly used in children diagnosed with central nervous system malformation (17.6%), and monotherapy was the prevailing dosage (55.9%). LEV was used for focal seizures in 50% of cases. Five children (7.3%) had psychiatric disorders, classified as probable adverse drug reactions. Conclusion. LEV was used in children with various diagnoses, with a low rate of adverse events. The profile of drug use varied in the different age groups. Future studies are needed to identify effectiveness, especially in newborn infants and patients with refractory epilepsy.

Overnight Electroencephalogram to Forecast Epilepsy Development in Children with Autism Spectrum Disorders.

OBJECTIVE: To establish the utility of long-term electroencephalogram (EEG) in forecasting epilepsy onset in children with autism spectrum disorder (ASD). STUDY DESIGN: A single-institution, retrospective analysis of children with ASD, examining long-term overnight EEG recordings collected over a period of 15 years, was conducted. Clinical EEG findings, patient demographics, medical histories, and additional Autism Diagnostic Observation Schedule data were examined. Predictors for the timing of epilepsy onset were evaluated using survival analysis and Cox regression. RESULTS: Among 151 patients, 17.2% (n = 26) developed unprovoked seizures (Sz group), while 82.8% (n = 125) did not (non-Sz group). The Sz group displayed a higher percentage of interictal epileptiform discharges (IEDs) in their initial EEGs compared with the non-Sz group (46.2% vs 20.0%, P = .01). The Sz group also exhibited a greater frequency of slowing (42.3% vs 13.6%, P < .01). The presence of IEDs or slowing predicted an earlier seizure onset, based on survival analysis. Multivariate Cox proportional hazards regression revealed that the presence of any IEDs (HR 3.83, 95% CI 1.38-10.65, P = .01) or any slowing (HR 2.78, 95% CI 1.02-7.58, P = .046 significantly increased the risk of developing unprovoked seizures. CONCLUSION: Long-term EEGs are valuable for predicting future epilepsy in children with ASD. These findings can guide clinicians in early education and potential interventions for epilepsy prevention.

The reality of epilepsy in primary care in Rio de Janeiro: the importance of educational projects for better patient care.

BACKGROUND: The Basic Health Unit (Unidade Básica de Saúde - UBS, in Portuguese) is the first point of contact in the public healthcare system for people with epilepsy. Primary care professionals need to appropriately diagnose, treat, and refer, if necessary, to tertiary services. OBJECTIVE: To evaluate the knowledge of UBS professionals on the management of patients with epilepsy in Rio de Janeiro. METHODS: Online questionnaires were performed on the topic of epilepsy before and after exposure to classes taught by epileptologists. RESULTS: A total of 66 doctors participated, 54.5% of whom were residents or trained in family medicine. The majority had from 1 to 3 years of practice. Insecurity prevailed in the management of pregnant women and the elderly. Around 59.1% of the participants referred patients with seizures without examinations. A total of 78% of the participants did not correctly classify seizure types, and 2/3 did not define drug-resistant epilepsy. Induction and broad-spectrum drugs were common. The therapeutic decision depended on availability in the basic health unit (UBS) (81.8%), dosage (60.6%), side effects (34.8%), and age (36.4%). Comorbidities and sex influenced 1/4 of the sample. For 23% of the participants, the type of crisis did not affect the choice. Regarding typical non-pharmacological options, 75% of the participants were aware of cannabidiol, 40.9% of surgery, 22.7% of ketogenic diet, and 22.8% of deep brain stimulation/vagus nerve stimulation (DBS/VNS). A total of 90.2% indicated the need for training. CONCLUSION: There are deficits in the knowledge of UBS professionals in the management of epilepsy. Specialized training is imperative to optimize the care offered within SUS.

ANTECEDENTES: A Unidade Básica de Saúde (UBS) é o primeiro contato no sistema público de saúde para pessoas com epilepsia. Profissionais de atenção primária precisam diagnosticar, tratar e encaminhar adequadamente, se necessário, a serviços terciários. OBJETIVO: Avaliar o conhecimento dos profissionais das UBSs sobre o manejo de pacientes com epilepsia no Rio de Janeiro. MéTODOS: Foram realizados questionários online sobre o tema da epilepsia pré e pós exposição a aulas ministradas por epileptólogos. RESULTADOS: Participaram 66 médicos, sendo 54,5% residentes ou formados em medicina da família. A maioria tinha de 1 a 3 anos de prática. A insegurança prevaleceu no manejo de gestantes e idosos. Cerca de 59,1% dos participantes encaminhavam pacientes com crises sem exames. Um total de 78% dos participantes não classificou corretamente tipos de crises, e 2/3 não definiram epilepsia farmacorresistente. Fármacos indutores e de amplo espectro foram comuns. A decisão terapêutica dependeu da disponibilidade na Unidade Básica de Saúde (UBS) (81,8%), posologia (60,6%), efeitos colaterais (34,8%) e idade (36,4%). Comorbidades e sexo influenciaram 1/4 da amostra. Para 23% dos participantes, o tipo de crise não afetou a escolha. Quanto a opções não farmacológicas típicas, 75% conheciam o canabidiol, 40,9% a cirurgia, 22,7% a dieta cetogênica, 22,8% a estimulação cerebral profunda/estimulação do nervo vago (ECP/ENV). Um total de 90,2% dos participantes indicou necessidade de treinamento. CONCLUSãO: Há déficits no conhecimento dos profissionais das UBSs no manejo da epilepsia. O treinamento especializado é imperativo para otimizar o cuidado oferecido no âmbito do SUS.

Neuropsychological profile in tuberous sclerosis complex: a study of clinical and cognitive variables in a cohort from Brazil.

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.

An update on the novel methods for the discovery of antiseizure and antiepileptogenic medications: where are we in 2024?

INTRODUCTION: Despite the availability of around 30 antiseizure medications, 1/3 of patients with epilepsy fail to become seizure-free upon pharmacological treatment. Available medications provide adequate symptomatic control in two-thirds of patients, but disease-modifying drugs are still scarce. Recently, though, new paradigms have been explored. AREAS COVERED: Three areas are reviewed in which a high degree of innovation in the search for novel antiseizure and antiepileptogenic medications has been implemented: development of novel screening approaches, search for novel therapeutic targets, and adoption of new drug discovery paradigms aligned with a systems pharmacology perspective. EXPERT OPINION: In the past, worldwide leaders in epilepsy have reiteratively stated that the lack of progress in the field may be explained by the recurrent use of the same molecular targets and screening procedures to identify novel medications. This landscape has changed recently, as reflected by the new Epilepsy Therapy Screening Program and the introduction of many in vitro and in vivo models that could possibly improve our chances of identifying first-in-class medications that may control drug-resistant epilepsy or modify the course of disease. Other milestones include the study of new molecular targets for disease-modifying drugs and exploration of a systems pharmacology perspective to design new drugs.

Translation to Portuguese and cross-cultural adaptation of the epilepsy transition readiness checklist for use in Brazil.

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.