Epilepsia refractaria con convulsiones febriles plus en niños con mutaciones de la subunidad alfa de canales de sodio (SCN1A): un reporte de caso / Refractory epilepsy with febrile seizures in a child with sodium channel alpha subunit mutation (SCN1A): A case report

RESUMEN Se presenta caso de una niña de 10 años con cuadro de epilepsia mioclónica juvenil severa en la infancia, que a los 6 meses de edad debutó con crisis tónico-clónicas generalizadas (TCG) luego de la administración de una dosis de vacuna DPT, con posteriores crisis TCG, mioclónicas y múltiples episodios de estado epiléptico refractarios a fármacos antiepilépticos (FAE) de primera y segunda línea durante los primeros 5 años. Las crisis se asociaron a retraso global en el desarrollo luego del primer episodio. Durante la evolución se realizaron estudios que incluyen resonancia magnética cerebral que fue normal y tomografía por emisión de positrones (PET-CT) que evidenció alteraciones en el metabolismo en región temporal izquierda, además de estudios para inmunodeficiencias y trombofilias sin alteraciones. Los electroencefalogramas iniciales fueron normales, pero video electroencefalograma de 12 horas mostró actividad irritativa en la región central con diseminación bilateral. Los estudios genéticos identificaron una mutación en el marco de lectura de tipo "frameshift" del gen SCN1A mediante secuenciación de la región codificante. Luego de los primeros años de vida, la paciente presenta, atípicamente, remisión progresiva de las crisis con posterior desmonte de FAE y mejoría del neuro-desarrollo en el proceso interdisciplinario de rehabilitación.

SUMMARY We report the case of a 10-year-old female with a history of severe myoclonic epilepsy of infancy who presents with generalized tonic-clonic (GTC) seizures at 6 months of age after administration of a DPT vaccine, who then begins to present frequent and severe GTC seizures, myoclonic seizures and multiple refractory status epilepticus poorly controlled with first and second line anti-epileptic drugs (AEDs). This was accompanied by development delay. Studies performed on the patient included brain MRI which was normal, immunodeficiency and trombophilic studies which were normal and electroencephalographs: studies (EEG) that were at first mostly normal. The most significant findings were seen during a 12-hour video-EEG which reported epileptogenic activity in central region with bilateral dissemination and a PET-CT that showed metabolism alterations in the left temporal region. Due to this presentation a channelopathy was suspected and a coding region sequentiation study was performed which identified a frameshift mutation of the SCN1A gene confirming the diagnosis. Atipically, after 5 years the patient begins to present a favorable evolution with significant seizure remission even allowing the progressive weaning of AEDs and a remarkable stalemate of developmental delay after interdisciplinary rehabilitation process was started.

Investigation of magnetic resonance imaging texture analysis as an aid tool for characterization of refractory epilepsies / Investigacao da analise de textura em imagem de ressonancia magnetica como auxilio para caracterizacao de epilepsias refratarias

Refractory epilepsies are syndromes for which therapies that employ two or more antiepileptic drugs, separately or in association, do not result in control of crisis. Patients may present focal cortical dysplasia or diffuse dysplasia and/or hippocampal atrophic alterations that may not be detectable by a simple visual analysis in magnetic resonance imaging. The aim of this study was to evaluate MRI texture in regions of interest located in the hippocampi, limbic association cortex and prefrontal cortex of 20 patients with refractory epilepsy and to compare them with the same areas in 20 healthy individuals, in order to find out if the texture parameters could be related to the presence of the disease. Of the 11 texture parameters calculated, three indicated the existence of statistically significant differences between the studied groups. Such findings suggest the possibility of this technique contributing to studies of refractory epilepsies.

Epilepsias refratárias compreendem síndromes para as quais as terapias que empregam duas ou mais drogas antiepilépticas, isoladamente ou em associação, não resultam no controle da frequência das crises. Portadores podem apresentar displasias corticais focais ou difusas e/ou alterações atróficas hipocampais que, em alguns casos, não são detectáveis por uma simples análise visual nas imagens de ressonância magnética. Nesse contexto, o objetivo deste estudo foi avaliar a textura de imagens de RM em regiões de interesse localizadas nos hipocampos, córtex de associação límbico e córtex pré-frontal de 20 pacientes com epilepsia refratária e compará-las às mesmas áreas de um grupo de 20 indivíduos sadios. Dos 11 parâmetros de textura calculados, três indicaram a existência de diferenças estatisticamente significantes entre os grupos estudados. Tais achados sugerem a possibilidade desta técnica contribuir para os estudos das epilepsias de difícil controle.

The effect of zonisamide in children with refractory epilepsies

Zonisamide was administered to 20 patients with refractory epileptic seizures. The mean duration of the administration was 6 months, and the mean dosage was 7.2 mg/kg/day. The efficacy of zonisamide was rated remarkable in 15% of the cases, improvement in 40%, and no change in 45%. The response rates of zonisamide were 62.5% for myoclonic seizures, 50% for tonic-clonic seizures, 80% for atonic seizures and 33.3% for atypical absence seizures. There was no correlation between the clinical response and dose or serum concentration of the drug. The adverse effects were observed in 35% of the cases which were drowsiness, dizziness, ataxia, nausea, and vomiting. In all cases, however, the administration of zonisamide could be continued.