Anterior thalamic nuclei deep brain stimulation inhibits mossy fiber sprouting via 3',5'-cyclic adenosine monophosphate/protein kinase A signaling pathway in a chronic epileptic monkey model / 中华医学杂志(英文版)

BACKGROUND@#Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.@*METHODS@#Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.@*RESULTS@#ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).@*CONCLUSION@#ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

Hippocampus chronic deep brain stimulation induces reversible transcript changes in a macaque model of mesial temporal lobe epilepsy / 中华医学杂志(英文版)

BACKGROUND@#Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level.@*METHODS@#We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses.@*RESULTS@#The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance.@*CONCLUSION@#Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.

O Methohexital Sódico (Brevital) no Teste de Wada: relato de dois casos / The sodium methohexital (Brevital) in Wada's test: report of two cases

O Teste de Wada continua sendo um exame frequentemente utilizado, para a avaliação qualitativa e quantitativa da lateralidade das funções de linguagem e das funções de memória verbal, e do possível déficit residual, uma vez que simula o efeito da cirurgia na investigação pré-operatória de candidatos a lobectomia temporal. No Brasil, há consideráveis dificuldades impostas pelas autoridades sanitárias para obtenção do Amytal (amobarbital sódico). Descreve o protocolo do Teste de Wada realizado com Brevital (methoexital sódico) em dois candidatos a lobectomia temporal, comentar sua eficácia e suas diferenças em relação ao realizado com o Amytal. Relatou-se o uso do Brevital em dois pacientes submetidos a determinação da lateralidade da linguagem e da memória através de protocolo adaptado pata tal. O Brevital, um anestésico de ação curta, mostrou-se eficiente em ambos os casos como substituto ao Amytal. O Brevital pode ser utilizado no Brasil para a realização do Teste de Wada, com a vantagem de possibilitar um exame mais breve, assim como uma investigação abrangente das funções de memória

Sindrome de la esclerosis mesial temporal en pacientes adultos / Mesial temporal sclerosis syndrome in adult patients

Las imágenes por resonancia magnética (IRM) resultan una herramienta esencial en el estudio de pacientes con epilepsia. Desde su aplicación, es posible detectar lesiones, como la esclerosis hipocampal (EH), que antes eran reconocidas sólo en exámenes anatomopatológicos. El objetivo de este estudio fue analizar las manifestaciones clínicas, electroencefalográficas y evolución de la epilepsia en pacientes con diagnóstico de EH realizado a través de las IRM. Se revisaron 384 historias de pacientes del Centro de Epilepsia, Hospital Ramos Mejía, que contaban con un estudio de IRM. De ellos 35 (15.5 por ciento), tenían diagnóstico de EH, sobre la base de los cambios estructurales observados en las imágenes. Seis pacientes fueron excluidos por falta de datos clínicos. De los 29 restantes, 15 eran hombres. El promedio de edad fue de 32.7 + 10.2 años (límites: 19-58). Todos los pacientes tenían crisis parciales. Diez (34.5 por ciento) habían tenido convulsiones febriles en la infancia. El EEG interictal mostró anormalidades focales que fueron coincidentes en lateralidad con los hallazgos de las IRM en 16 pacientes (55.1 por ciento). Catorce enfermos (48.3 por ciento) tenían la lesión del lado derecho en las IRM, trece del lado izquierdo (44.9 por ciento) y en 2 casos era bilateral (6.8 por ciento). Veintisiete pacientes (93.1 por ciento) eran refractarios al tratamiento. En 3 casos se realizó una lobectomía temporal anterior, con buena evolución posterior. La identificación de estos pacientes, que presentan determinadas características clínicas, junto con los hallazgos en las IRM, definen al síndrome de la esterosis mesial temporal. Esto permite beneficiar a estos enfermos a fin de establecer el progóstico de la epilepsia y definir su tratamiento específico.

Epilepsia do lobo temporal em psiquiatria / Temporal lobe epilepsy in psychiatry

A epilepsia do lobo temporal é uma das principais condiçöes médicas que o psiquiatra deve afastar durante a avaliaçäo de pacientes com transtornos mentais. Os autores realizam breve revisäo da literatura sobre a história, fisiopatologia, diagnóstico e tratamento das crises epilépticas do lobo temporal, enfatizando os aspectos psicopatógicos e o diagnóstico diferencial com transtornos psiquiátricos como o pânico e a esquizofrenia. Dentre os avanços na área, a ressonância nuclear magnética tem demonstrado eficiência diagnóstica superior à da tomografia computadorizada na detecçäo da esclerose temporal mesial - a causa mais freqüente de epilepsia do lobo temporal. A detecçäo da esclerose temporal mesial é importante devido à freqüente indicaçäo de cirurgia nesses casos

Epilepsia temporal: hepar sulphur, un caso clínico, dosis única / Temporal epilepsy: hepar sulphur, clinical case, single dose

En este trabajo se relata el caso de un paciente adolescente con antecedentes de epilepsia temporal desde la infancia, corroborada por electroencefalograma, y trastornos de la conducta grave que requieren intervención policial. Medicado con Hepar sulphur en dosis única, mejora su conducta y normaliza el electroencefalograma. Se trata de un caso con 4½ años de control