The role of eletrical synapses in epileptic seizures

INTRODUÇÃO: No sistema nervoso central a comunicação entre neurônios se realiza através de estruturas denominadas sinapses: elétricas ou químicas. As sinapses elétricas são formadas pela aproximação das membranas plasmáticas de dois neurônios formando estruturas chamadas junções comunicantes (gap junctions, do inglês). As junções comunicantes são compostas por seis subunidades da proteína conexina de cada membrana, formando poros que comunicam o citoplasma de células adjacentes e permitem a passagem de íons e pequenas moléculas. OBJETIVOS: A presente revisão pretende descrever e discutir os principais resultados que apontam para uma importante relação entre junções comunicantes e sincronia neuronal durante crises epilépticas. RESULTADOS E CONCLUSÃO: Quando um neurônio é despolarizado, este tipo de comunicação permite a rápida transferência iônica entre as células, promovendo alta sincronia neuronal. Recentemente, o papel das junções comunicantes na geração e propagação de descargas epilépticas tem sido estudado através do uso de diferentes modelos experimentais in vivo, in vitro e in silico (modelos computacionais).INTRODUCTION: In the central nervous system, neuronal communication is accomplished by structures called synapses: electrical or chemical. Electrical synapses are formed by the apposition of plasmatic membranes at gap junctions and the interaction of connexin subunits from two neurons. At this site, connexin complexes create intercellular pores that communicate the cytoplasm of adjacent neurons and allow free flow of ions and small molecules. OBJECTIVE: In this review, we will present and discuss recent results showing the possible involvement of electrical synapses in the neuronal hypersynchronization during epileptic seizures. RESULTS AND CONCLUSION: When a neuron is depolarized, ions flow very rapidly from one cell to the other promoting high neuronal synchrony. More recently, the role of gap junctions in the generation and propagation of epileptic discharges has been investigated using combined approaches of in vivo, in vitro and in silico (computational) models

Ativação variável da ressonância magnética funcional com duas tarefas diferentes em um paciente com retardo mental

Functional MRI produces a more accurate localization of the language areas for epilepsy surgery purpose, but requires the patient cooperation. We report a 34 years-old woman with mental retardation who underwent two different verbal fluency tasks, category and word naming. We found a strong activation of the Broca’s area in the most difficult task. We suggest that a multi-task fMRI study could be successful in patients with cognitive delay.A ressonância magnética funcional permite uma localização acurada da área da linguagem para fins de cirurgia de epilepsia, mas requer a colaboração do paciente na execução da tarefa proposta, o que pode limitar a sua utilização em pacientes com retardo mental. Nós apresentamos o caso de uma mulher com 34 anos de idade, com retardo mental, que foi submetida a duas tarefas distintas de geração silenciosa de palavras, por categoria e letras. Encontramos forte ativação da área de Broca na tarefa mais complexa. Sugerimos que um estudo com múltiplas tarefas pode ser útil em pacientes com retardo mental

Multimodal quantitative magnetic resonance imaging analysis with individualized postprocessing in patients with drug-resistant focal epilepsy and conventional visual inspection negative for epileptogenic lesions

OBJECTIVES: Approximately one-third of candidates for epilepsy surgery have no visible abnormalities on conventional magnetic resonance imaging. This is extremely discouraging, as these patients have a less favorable prognosis. We aimed to evaluate the utility of quantitative magnetic resonance imaging in patients with drug-resistant neocortical focal epilepsy and negative imaging. METHODS: A prospective study including 46 patients evaluated through individualized postprocessing of five quantitative measures: cortical thickness, white and gray matter junction signal, relaxation rate, magnetization transfer ratio, and mean diffusivity. Scalp video-electroencephalography was used to suggest the epileptogenic zone. A volumetric fluid-attenuated inversion recovery sequence was performed to aid visual inspection. A critical assessment of follow-up was also conducted throughout the study. RESULTS: In the subgroup classified as having an epileptogenic zone, individualized postprocessing detected abnormalities within the region of electroclinical origin in 9.7% to 31.0% of patients. Abnormalities outside the epileptogenic zone were more frequent, up to 51.7%. In five patients initially included with negative imaging, an epileptogenic structural abnormality was identified when a new visual magnetic resonance imaging inspection was guided by information gleaned from postprocessing. In three patients, epileptogenic lesions were detected after visual evaluation with volumetric fluid-attenuated sequence guided by video electroencephalography. CONCLUSION: Although quantitative magnetic resonance imaging analyses may suggest hidden structural lesions, caution is warranted because of the apparent low specificity of these findings for the epileptogenic zone. Conversely, these methods can be used to prevent visible lesions from being ignored, even in referral centers. In parallel, we need to highlight the positive contribution of the volumetric fluid-attenuated sequence

Increased Metallothionein I/II Expression in Patients with Temporal Lobe Epilepsy

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) and patients with TLE associated with tumor or dysplasia (TLE-TD) were evaluated for expression of MT-I/II, for the vesicular zinc levels, and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis, microgliosis and reduced neuronal population. In TLE-TD, the same changes were observed, except that were mainly confined to fascia dentata. Increased vesicular zinc was observed only in the inner molecular layer of MTLE patients, when compared to control cases. Correlation and linear regression analyses indicated an association between increased MT-I/II and increased astrogliosis in TLE. MT-I/II levels did not correlate with any clinical variables, but MTLE patients with secondary generalized seizures (SGS) had less MT-I/II than MTLE patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from TLE patients and our data suggest that it is associated with astrogliosis and may be associated with different seizure spread patterns.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2005/56447-7, 2009/53447-7, 2008/52657-5]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

On the relationship between neurocysticercosis and mesial temporal lobe epilepsy associated with hippocampal sclerosis: coincidence or a pathogenic relationship?

Neurocysticercosis (NCC) and mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) are two common worldwide forms of focal epilepsy. In regions where NCC is endemic, both diseases can be observed in the same patient. There is recent and growing evidence suggesting that NCC might contribute to or even cause MTLE-HS. In this article, we review the literature regarding NCC and temporal lobe epilepsy, specifically addressing the relationship between NCC and MTLE-HS. In addition, we review some scenarios where NCC seems to emerge as a causative agent or contributor to the development of MTLE-HS in some patients. This association is important because it may have an impact on the evaluation and treatment of a sizable proportion of patients with epilepsy. Insights from these clinical observations might also contribute to the understanding of the neurobiology of both NCC and MTLE-HS. We hope that our review might shed some light on this interesting interplay between two of the most common worldwide conditions associated with human focal epilepsy.Brazilian governmentBrazilian governmentFAPESP/CINAPCE Project [04/14004-9]FAPESP/CINAPCE ProjectCNPqCNPq [306644/2010-0, 483108/2010-3]FAPERGS/CNPq PRONEM grantFAPERGS/CNPq PRONEM gran