Prophylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice.

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans.

Epilepsy awareness days, weeks, and months: Their roles in the fight against epilepsy and the intersectoral global action plan on epilepsy and other neurological disorders.

OBJECTIVES: This research sought to find out the epilepsy awareness days around the world and understand the nature and role of the days in the fight against epilepsy in relation to the Intersectoral Global Action Plan (IGAP) on epilepsy and other neurological disorders (2022-2031). METHODS: We conducted a review of journal articles. The databases that we searched were ProQuest Central, EBSCOhost Academic Search Complete, EBSCO Medline, PubMed Central, Wiley Online, Directory of Open Access Journals (DOAJ), African Journals Online (AJOL), and Google Scholar. We limited our search to papers of relevance to our subject published between January 2000 and January 2023. We searched 'epilepsy awareness day, week, or month'. From the databases, 13 articles met our inclusion criteria. We augmented our results with a search on Google of articles about epilepsy awareness day, week, or month. We also searched directly on the websites of epilepsy organizations. RESULTS: We found that epilepsy awareness days fall into these categories: global awareness days (n = 2), awareness months (n = 4), regional awareness weeks (n = 5), and regional awareness days (n = 1). Our search for national awareness days (n = 7) was not comprehensive, and this could be an area for future research. The literature shows that epilepsy awareness days could play a role in (1) reducing knowledge and treatment gaps, (2) increasing participation, (3) unlocking resources, and (4) necessitating policy change and increasing networking. The major role of these dedicated days in the IGAP is to accelerate awareness and advocacy for policy change and improved interventions. CONCLUSIONS: Epilepsy awareness days are bringing stakeholders together already, and IGAP initiatives could tap into this achievement to accelerate awareness in a cost effective, contextual and collaborative manner. This could be achieved by adopting themes that relate more directly to the IGAP goals. Another important strategy is to motivate countries that do not have national epilepsy days or regions that do not have a regional awareness days, to consider doing one within the confines of resources.

Vigabatrina comparado con hormona adrenocorticotrópica para el tratamiento de espasmos infantiles y Síndrome de West / Vigabatrin compared with adrenocorticotropic hormone for the treatment of infantile spasms and West Syndrome

OBJETIVO: Determinar los riesgos y beneficios del uso de vigabatrina comparada con hormona adrenocorticotrópica (ACTH) para el tratamiento de espasmos infantiles. MÉTODO: Se realizó una búsqueda en Epistemonikos. Se extrajeron datos desde las revisiones identificadas. Se realizó un metaanálisis a partir de estudios primarios y se utilizó el método GRADE para la presentación de resultados. RESULTADOS: Se identificaron nueve revisiones sistemáticas. Se observó que el uso de vigabatrina en comparación con ACTH disminuye la resolución de espasmos (RR 0,8, IC 95% 0,65 - 0,98) y podría disminuir la resolución de hipsarritmia (RR 0,71, IC 95% 0,48 - 1,05). No fue posible determinar si el uso de vigabatrina disminuye el riesgo de desarrollar efectos adversos (RR 0,75, IC 95% 0,23 - 2,45) por certeza de evidencia muy baja. CONCLUSIONES: La evidencia parece inclinarse a favor del uso de ACTH. Sin embargo debe considerarse la necesidad de nuevas investigaciones para esclarecer su seguridad.

OBJECTIVE: To determine the risks and benefits of the use of vigabatrin compared to ACTH for the treatment of infantile spasms. METHOD: A search in Epistemonikos was performed. Data were extracted from the identified reviews. A meta-analysis was performed from primary studies and the GRADE method was used to present the results. RESULTS: Nine systematic reviews were identified. Vigabatrin use compared to ACTH was found to decrease resolution of spasms (RR 0.8, 95% CI 0.65 - 0.98) and might decrease resolution of hypsarrhythmia (RR 0.71, 95% CI 0 .48 - 1.05). It was not possible to determine whether the use of vigabatrin reduces the risk of developing adverse effects (RR 0.75, 95% CI 0.23 - 2.45) due to very low certainty of evidence. CONCLUSIONS: The evidence seems to lean in favor of the use of ACTH. However, the need for new research should be considered to clarify its safety.

Alteraciones electrocardiográficas periictales en pacientes pediátricos con epilepsia. Un estudio prospectivo / Peri-ictal electrocardiographic alterations in paediatric epilepsy patients. A prospective study

INTRODUCCIÓN: Las crisis epilépticas pueden asociarse a alteraciones del ritmo cardíaco periictales e incluso a muerte súbita (SUDEP). Existen escasos estudios pediátricos al respecto. OBJETIVO: Determinar las alteraciones del ritmo cardíaco en pacientes pediátricos con epilepsia estudiados con videoelectroencefalograma (video-EEG). MÉTODOS: Estudio prospectivo, observacional, en pacientes menores de 18 años ingresados para video-EEG en el Hospital Clínico Red de Salud UC-Christus, Santiago, Chile. Se realizó una evaluación neurológica y cardiológica, electrocardiograma (ECG) y Holter ECG simultáneo al video-EEG. RESULTADOS: Se estudió a 25 pacientes, 12 con epilepsias refractarias, 23/25 focales y 20 en tratamiento con politerapia. Se registraron 768 horas de video-EEG, incluyendo 281 crisis epilépticas en 15 pacientes: 157 clínicas y 103 generalizadas. No hubo arritmias graves; sólo alteraciones inespecíficas o probablemente benignas, principalmente bloqueo incompleto de la rama derecha en 11 pacientes, más frecuente en las epilepsias refractarias (p < 0,036). La variación de la frecuencia cardíaca ocurrió principalmente en crisis > 30 segundos. Ningún paciente ha presentado SUDEP. CONCLUSIONES: Éste es el primer estudio prospectivo, con una nueva técnica, usando simultáneamente video-EEG y Holter ECG en pediatría. Pese al alto número de crisis y pacientes refractarios, no encontramos alteraciones graves del ritmo cardíaco, en concordancia con la evaluación clínica. El bloqueo de la rama derecha se considera un hallazgo cardiológico no patológico, pero tuvo una alta prevalencia en nuestra muestra, comparada con la población normal, especialmente en la epilepsia refractaria. Dado que la SUDEP es un evento grave en la epilepsia, es importante ahondar más en este tipo de estudios para evaluar medidas preventivas

INTRODUCTION: Epileptic seizures can be associated with peri-ictal heart rhythm disorders and even sudden death (SUDEP). Few paediatric studies have been conducted on the subject. AIM: To determine heart rhythm disorders in paediatric patients with epilepsy who were studied with video-electroencephalogram (video-EEG). METHODS: Prospective, observational study in patients under 18 years of age admitted for video-EEG at the Hospital Clínico Red de Salud UC-Christus, Santiago, Chile. A neurological and cardiological evaluation and electrocardiogram (ECG) were performed, in addition to a Holter ECG simultaneously with the video-EEG. RESULTS: Twenty-five patients were studied, 12 with refractory epilepsies, 23/25 focal and 20 on polytherapy. Altogether 768 hours of video-EEG were recorded, including 281 seizures in 15 patients: 157 clinical and 103 generalised. There were no serious arrhythmias, only non-specific or probably benign disorders, mainly incomplete right bundle branch block in 11 patients, which were more frequent in refractory epilepsies (p < 0.036). Heart rate variation occurred mainly in seizures >30 seconds. No patient presented SUDEP. CONCLUSIONS: This is the first prospective study, with a new technique, using video-EEG and Holter ECG simultaneously in paediatrics. Despite the high number of seizures and refractory patients, we found no serious heart rhythm disorders, consistent with the clinical evaluation. Right bundle branch block is considered a non-pathological cardiological finding, but was highly prevalent in our sample compared to the normal population, especially in refractory epilepsy. Given that this is a serious event in epilepsy, it is important to further investigate such studies to assess preventive measures

Epilepsia y pandemia por COVID-19: recomendaciones para un manejo integral / Epilepsy and pandemic by COVID-19: recommendations for an integral management

La pandemia de COVID-19, nos ha enfrentado una situación de emergencia que ha impactado múltiples aspectos de la vida diaria y además dificultades asociadas al manejo de las enfermedades crónicas como la epilepsia, en la cual la adherencia al tratamiento, los costos y las comorbilidades, juegan un rol importante. También el personal que trabaja o que atiende a los pacientes con epilepsia, su entorno y familiares han debido modificar su accionar. Hay pacientes, que han mejorado el control de sus crisis por diferentes motivos y otros en cambio, han empeorado y además han evolucionado con mayor ansiedad. El objetivo de este artículo es revisar diferentes elementos a considerar en el manejo de las epilepsias en el contexto de la pandemia por COVID-19.

The COVID-19 pandemic has faced us with an emergency situation that has impacted multiple aspects of daily life and also difficulties associated with the management of chronic diseases such as epilepsy, in which adherence to treatment, costs and comorbidities, play an important role. Also, the staff who work with or care for patients with epilepsy, their environment and family members have had to modify their actions. There are patients, who have improved the control of their seizures for different reasons while others have worsened and have also presented with greater anxiety. The objective of this article is to review different elements to consider in the management of epilepsy in the context of the Pandemic by COVID-19.

Efectos Adversos del Tratamiento con Vigabatrina en Síndrome de West: reporte de 2 casos / Adverse Effects of Vigabatrin Use for West Syndrome treatment: a report of 2 Clinical Cases

El síndrome de West (SW) es un síndrome epiléptico de la infancia temprana. Dentro de los fármacos de primera línea utilizados para su tratamiento se encuentran la hormona adrenocorticotropa (ACTH) y Vigabatrina. Estudios sugieren igual efectividad en el uso a largo plazo de ambos para controlar el SW. En Chile, el uso de Vigabatrina ha aumentado dada su mayor disponibilidad, facilidad de uso y menor costo. Se describen 2 casos clínicos presentando complicaciones agudas infrecuentes secundarias a su uso. Ambos pacientes con antecedentes de SW y trisomía 21. Primer caso: Lactante de 11 meses que inicia tratamiento con 100 mg/kg/día de Vigabatrina a los 7 meses, aumentando a 150 mg/kg/día por mala respuesta. Evolucionó con un síndrome extrapiramidal, con alteraciones radiológicas características. Segundo caso: Lactante de 7 meses, que tras iniciar tratamiento con vigabatrina (100 mg/kg/día) desarrolla rash facial sugerente de hipersensibilidad a fármacos antiepilépticos (FAEs), sin compromiso mucoso ni alteraciones sistémicas. Ambas regresan a su basal luego de suspensión o disminución de dosis del medicamento. Destaca la importancia de la monitorización de efectos adversos en el uso de FAEs y atender la aparición de reacciones poco conocidas. Las alteraciones imagenológicas por Vigabatrina son conocidas, no así el síndrome extrapiramidal asociado (primer caso). Por otra parte, las reacciones cutáneas están ampliamente descritas para múltiples FAEs, pero no para Vigabatrina (segundo caso). Dado el uso frecuente de Vigabatrina para tratar SW y otras epilepsias, es fundamental conocer y manejar reacciones adversas poco conocidas como las aquí presentadas. Palabras claves: Síndrome de West, Síndrome de Down, espasmos infantiles, vigabatrina, reacciones adversas, toxicidad, alergia, rash.

West Syndrome is an epileptic syndrome which typically presents in early childhood. In regard to treatment, the first line includes adrenocorticotropic hormone (ACTH) and Vigabatrin. Studies suggest similar response in the long term to both treatments. In Chile, Vigabatrin is being used more frequently as it is more available, of easier administration and lower cost. We present in the following report 2 clinical cases that presented acute infrequent complications secondary to its use in patients with both Down and West Syndrome. First case: 11-month-old infant who was initially treated with 100mg/kg/day of Vigabatrin at 7 months of age and increased to 150mg/kg/day due to lack of response. She evolved with an extrapyramidal syndrome with radiological manifestations. The second case: 7-month old toddler who initiated treatment with 100mg/kg/day of Vigabatrin and developed a facial rash, suggestive of hypersensitivity to antiepileptic drugs, with no mucosal or systemic involvement. Both patients returned to their previous condition shortly after Vigabatrin was decreased or discontinued. We emphasize the importance of the early monitorization of adverse effects in the use of antiepileptic drugs and awareness of less common reactions. Radiological findings associated with the use of Vigabatrin are well known, but not the clinical evolution with symptomatic extrapyramidal symptoms, as in the first case. Allergic reactions to the use of antiepileptic drugs have also been reported to several drugs, but not to Vigabatrin (second case). As Vigabatrin is being used more frequently to treat WS and other epilepsies it is important to know and manage uncommon adverse reactions as the ones presented in this report. Keywords: West Syndrome, Down Syndrome, infantile spasms, vigabatrin, adverse reactions, toxicity, allergy, rash

[Refractory status epilepticus in children: characterisation of epilepsies, continuous electroencephalographic monitoring and response to treatment]. / Estado epileptico refractario en ninos: caracterizacion de las epilepsias, monitorizacion electroencefalografica continua y respuesta al tratamiento.

INTRODUCTION: Patients with refractory status epilepticus (RSE) have high morbidity and mortality rates, are hospitalised for longer periods of time, suffer greater neurological damage and progress to symptomatic epilepsy. Continuous electroencephalogram (cEEG) monitoring is a valuable aid in the early detection of RSE, especially in the case of non-convulsive status epilepticus (NCSE). In this study we describe the clinical characteristics, treatment and use of cEEG in paediatric patients with RSE. PATIENTS AND METHODS: A retrospective study was conducted at the Hospital Clinico de la Pontificia Universidad Catolica de Chile between November 2005 and March 2011 in patients aged between 1 month and 15 years diagnosed with RSE and cEEG. Demographic characteristics, baseline and final conditions, and therapy were recorded. RESULTS: A total of 15 patients, 12 of whom were males, with a mean age of 4 years (1.5 months-13 years) were identified. Eight patients had a history of epilepsy. The most frequent aetiologies were progressive symptomatic and acute symptomatic. Convulsive epileptic status (CSE) was present in 11 patients and NCSE in the other four. During the cEEG, six of the 11 patients with CSE later progressed to NCSE. The mean amount of time with RSE was 10.2 days. Of the 15 patients, 13 responded to anticonvulsive drugs and the main secondary complications were respiratory depression and hypotension. Patients with CSE tended to evolve in a more torpid manner than patients with NCSE. On discharge from hospital, 13 patients (86.6%) presented new neurological deficit or difficult-to-manage epilepsy, one still had RSE and one died (6%). CONCLUSIONS: The aggregate neurological morbidity and mortality rates of RSE were high. The use of cEEG monitoring should be considered for use in the management of such cases of status epilepticus.

Estado epiléptico refractario en niños: caracterización de las epilepsias, monitorización electroencefalográfica continua y respuesta al tratamiento / Refractory status epilepticus in children: characterisation of epilepsies, continuous electroencephalographic monitoring and response to treatment

Introducción. Los pacientes con estados epilépticos refractarios (EER) tienen alta morbimortalidad, hospitalizaciones más prolongadas, mayor daño neurológico y evolución a epilepsia sintomática. La monitorización mediante electroencefalograma continuo (EEGc) es útil en la detección precoz del EER, especialmente el estado epiléptico no convulsivo (EENC). En este trabajo describimos las características clínicas, el tratamiento y el uso del EEGc en pacientes pediátricos con EER. Pacientes y métodos. Es un estudio retrospectivo realizado en el Hospital Clínico de la Pontificia Universidad Católica de Chile entre noviembre de 2005 y marzo de 2011, en pacientes de 1 mes a 15 años de edad, con diagnóstico de EER y EEGc. Se registraron características demográficas, condición basal y a la salida, y terapia. Resultados. Se identificaron 15 pacientes, 12 varones, con una edad promedio de 4 años (1,5 meses-13 años). Ocho pacientes tenían antecedente de epilepsia. Las etiologías más frecuentes fueron sintomática progresiva y sintomática aguda. Presentaron estado epiléptico convulsivo (EEC) 11 pacientes, y EENC, cuatro. Durante el EEGc, seis de los 11 pacientes con EEC evolucionaron posteriormente a EENC. El tiempo promedio de EER fue 10,2 días. De los 15 pacientes, 13 respondieron al uso de anticonvulsionantes, y las principales complicaciones secundarias fueron depresión respiratoria e hipotensión. Los pacientes con EEC tendieron a evolucionar más tórpidamente que los pacientes con EENC. En el momento del alta, 13 pacientes (86,6%) presentaron nuevo déficit neurológico o epilepsia de difícil manejo, uno persistió con EER y uno falleció (6%). Conclusiones. La morbilidad neurológica agregada y la mortalidad de los EER fueron altas. Debería considerarse el uso de la monitorización del EEGc en el manejo de estos estados epilépticos (AU)

Introduction. Patients with refractory status epilepticus (RSE) have high morbidity and mortality rates, are hospitalised for longer periods of time, suffer greater neurological damage and progress to symptomatic epilepsy. Continuous electroencephalogram (cEEG) monitoring is a valuable aid in the early detection of RSE, especially in the case of nonconvulsive status epilepticus (NCSE). In this study we describe the clinical characteristics, treatment and use of cEEG in paediatric patients with RSE. Patients and methods. A retrospective study was conducted at the Hospital Clínico de la Pontificia Universidad Católica de Chile between November 2005 and March 2011 in patients aged between 1 month and 15 years diagnosed with RSE and cEEG. Demographic characteristics, baseline and final conditions, and therapy were recorded. Results. A total of 15 patients, 12 of whom were males, with a mean age of 4 years (1.5 months-13 years) were identified. Eight patients had a history of epilepsy. The most frequent aetiologies were progressive symptomatic and acute symptomatic. Convulsive epileptic status (CSE) was present in 11 patients and NCSE in the other four. During the cEEG, six of the 11 patients with CSE later progressed to NCSE. The mean amount of time with RSE was 10.2 days. Of the 15 patients, 13 responded to anticonvulsive drugs and the main secondary complications were respiratory depression and hypotension.Patients with CSE tended to evolve in a more torpid manner than patients with NCSE. On discharge from hospital, 13 patients (86.6%) presented new neurological deficit or difficult-to-manage epilepsy, one still had RSE and one died (6%). Conclusions. The aggregate neurological morbidity and mortality rates of RSE were high. The use of cEEG monitoring hould be considered for use in the management of such cases of status epilepticus (AU)