RESUMO
Background: Generalized convulsive epilepsy (GCE), an important subtype of epilepsy, is a syndrome of neuronal dysfunction characterized by diffuse abnormal discharge of neurons within the brain. Compounding evidence suggests a correlation between epilepsy and inflammatory factors, for instance, cyclooxygenase-2, interleukin-1ß, and interleukin-6. Elevated levels of inflammatory factors have been observed in patients with epilepsy and several animal models. Therefore, inflammation may be closely associated with the pathogenesis and progression of GCE. However, the cause-and-effect relationship between the two is difficult to determine because of small sample sizes and confounding factors. Methods: To test for causality of the 41 cytokines on GCE, we conducted a two-sample Mendelian randomization (MR) based on the largest and latest genome-wide association study (GWAS) involving 290 cases and 453,521 European controls and a GWAS meta-analysis consisting of 41 cytokines from 8,293 individuals. Results: R confirmed a bidirectional causal link between cytokines and GCE. Genetically predicted increased levels of hepatocyte growth factor and decreased levels of eotaxin and interleukin-18 are associated with an increased risk of GCE (OR = 1.904, 95% CI = 1.019-3.561, p = 0.044; OR = 0.641, 95% CI = 0.417-0.984, p = 0.042; OR = 0.482, 95% CI = 0.251-0.927, p = 0.046). Furthermore, the presence of GCE is related to an increase in levels of multiple cytokines, such as macrophage inflammatory protein-1α, interleukin-12p70, interleukin-17, interleukin-1 receptor antagonist, and basic fibroblast growth factor (OR = 1.038, 95% CI = 1.005-1.073, p = 0.024; OR = 1.031, 95% CI = 1.009-1.054, p = 0.006; OR = 1.027, 95% CI = 1.002-1.053, p = 0.037; OR = 1.037, 95% CI = 1.003-1.072, p = 0.032; OR = 1.032, 95% CI = 1.000-1.066, p = 0.048; OR = 1.025, 95% CI = 1.003-1.048, p = 0026). Conclusion: A bidirectional causal link existed between inflammation and GCE. Detecting significantly altered factor concentrations may be of great significance for screening GCE and predicting their occurrence. Moreover, available pharmacological treatments for GCE are focused primarily on suppressing seizures. In future, altering the concentration of these cytokines in the body through targeted anti-inflammatory therapy to modify the epileptogenic mechanism and prevent the recurrence and refractoriness of GCE may become the key to new treatments.
RESUMO
INTRODUCCIÓN: El estatus epiléptico superrefractario se define como convulsiones de 24 horas o más posterior al uso de anestésicos generales. Se presenta el siguiente caso con el fin de discutir el uso de anticonvulsivantes y la importancia del manejo multidisciplinario. PRESENTACIÓN DEL CASO: Escolar masculino de 8 años con antecedentes mórbidos de epilepsiades de los 2 meses en tratamiento con ácido valproico, lamotrigina y clobazam por recurrencia de crisis hipotónicas. Se hospitaliza por crisis atónicas frecuentes y compromiso de conciencia, se inicia levetiracetam y se retira lamotrigina. Electroencefalograma (EEG) muestra actividad epileptiforme muy frecuente sin variación ingresándose a unidad cuidados intensivos para administración de metilprednisolona por 5 días y manejo del estatus epiléptico superrefractario con midazolam en infusión continúa. Nuevo EEG severamente patológico compatible con status epiléptico eléctrico generalizado por lo que se induce coma barbitúrico con diferentes esquemas de tiopental y ketamina con persistencia del patrón de estallido supresión. Tras lo cual se modifica esquema a propofol y topiramato manteniendo antiepilépticos de base. A los 2 días de uso, se suspende propofol por mala respuesta, tras lo cual presenta 2 crisis convulsivas iniciándose fenobarbital. Evoluciona deforma favorable, sin crisis epilépticas clínicas, por lo que se decide alta con ácido valproico, levetiracetam, fenobarbital y topiramato. DISCUSIÓN: La tórpida evolución del caso expuesto y la necesidad de múltiples esquemas farmacológicos dejan en evidencia la necesidad de disponer y conocer el modo de uso de un amplio arsenal de fármacos anticonvulsivantes
INTRODUCTION: Super-refractory status epilepticus is defined as a 24 hours or more lasting seizure after the use of anaesthetics. The following case is shown in order to discuss the use of anticonvulsants and the importance of multidisciplinary management. CASE REPORT: 8 year old male with morbid history of epilepsy since 2 months old treated with valproic acid, lamotrigine and clobazam for recurrent hypotonic crisis. Is hospitalized for frequent atonicseizures and impaired consciousness, levetiracetam is initiated and lamotrigine removed. Electroencephalogram (EEG) shows persistent very frequent epileptiform activity. Patient is admitted to the intensive care unit for administration of methylprednisolone for 5 days and management with continuous infusion of midazolam for the super-refractory status epilepticus. New severely abnormal EEG compatible with generalized electrical status epilepticus deciding to induce a barbiturate coma with different schemes of ketamine and thiopental. Because of persistent suppression burst patter whereupon scheme is changed to propofol and topiramte maintaining chronic antiepileptic. After 2 days of use, propofol is suspended for poor response, after which the patient presents 2 seizures beginning the use of phenobarbital. He evolved favourably, without clinical seizures, so it is decided hospital discharge with valproic acid, levetiracetam, phenobarbital and topiramate. DISCUSSION: The torpid case exposed and the lack for multiple drug regimens are evidence of the need of having a wide arsenal of anticonvulsant drugs and how to use them
