Epileptogenesis

About: Epileptogenesis is a research topic. Over the lifetime, 4218 publications have been published within this topic receiving 170809 citations.

Concise Review: Prospects of Stem Cell Therapy for Temporal Lobe Epilepsy

Abstract: Certain regions of the adult brain have the ability for partial self-repair after injury through production of new neurons via activation of neural stem/progenitor cells (NSCs). Nonetheless, there is no evidence yet for pervasive spontaneous replacement of dead neurons by newly formed neurons leading to functional recovery in the injured brain. Consequently, there is enormous interest for stimulating endogenous NSCs in the brain to produce new neurons or for grafting of NSCs isolated and expanded from different brain regions or embryonic stem cells into the injured brain. Temporal lobe epilepsy (TLE), characterized by hyperexcitability in the hippocampus and spontaneous seizures, is a possible clinical target for stem cell-based therapies. This is because these approaches have the potential to curb epileptogenesis and prevent chronic epilepsy development and learning and memory dysfunction after hippocampal damage related to status epilepticus or head injury. Grafting of NSCs may also be useful for restraining seizures during chronic epilepsy. The aim of this review is to evaluate current knowledge and outlook pertaining to stem cell-based therapies for TLE. The first section discusses the behavior of endogenous hippocampal NSCs in human TLE and animal models of TLE and evaluates the role of hippocampal neurogenesis in the pathophysiology and treatment of TLE. The second segment considers the prospects for preventing or suppressing seizures in TLE using exogenously applied stem cells. The final part analyzes problems that remain to be resolved before initiating clinical application of stem cell-based therapies for TLE.

Febrile Infection-Related Epilepsy Syndrome: Clinical Review and Hypotheses of Epileptogenesis.

Abstract: Febrile infection–related epilepsy syndrome (FIRES, AERRPS, or DESC) is one of the most severe, mostly irreversible, and presumably immune-mediated epileptic encephalopathies affecting healthy children. Refractory status epilepticus or a cluster of seizures start a few days after the onset of an acute febrile illness; however, encephalitis cannot be proved. Sequelae of FIRES are drug-resistant epilepsy and neuropsychological impairments occurring without latency. Clinical knowledge is limited because FIRES is sporadic and extremely rare. Therefore, based on literature and our data, this review includes clinical features, terminology, epidemiology, diagnostic criteria and procedures, differential diagnoses, acute and chronic therapeutic options, and outcome data. Particular attention is paid to the epileptogenesis. We hypothesize that FIRES is an immune but not an autoimmune disease and discuss GABAergic therapy at high doses, avoidance of burst-suppression coma, and early introduction of enteral or even parenteral ketogenic diet as the most promising treatment. The lack of evidence requires both a network and a multinational web-based clinical registry to define the clinical spectrum for improving diagnosis and treatment and at the very least, to clarify the cause of FIRES. We conclude that the term “fulminant inflammatory response epilepsy syndrome” may be more appropriate.

Development of Postinfection Epilepsy After Theiler's Virus Infection of C57BL/6 Mice

Abstract: Viral infection of the central nervous system can lead to long-term neurologic defects, including increased risk for the development of epilepsy. We describe the development of the first mouse model of viral-induced epilepsy after intracerebral infection with Theiler's murine encephalomyelitis virus. Mice were monitored with long-term video-electroencephalogram at multiple time points after infection. Most mice exhibited short-term symptomatic seizures within 3 to 7 days of infection. This was followed by a distinct latent period in which no seizures were observed. Prolonged video-electroencephalogram recordings at 2, 4, and 7 months after the initial infection revealed that a significant proportion of the mice developed profound, spontaneous epileptic seizures. Neuropathologic examination revealed hippocampal sclerosis in animals with epilepsy. Theiler's murine encephalomyelitis virus-infected C57BL/6 mice represent a novel "hit-and-run" model to investigate mechanisms underlying viral-induced short-term symptomatic seizures, epileptogenesis, and epilepsy. Importantly, this model will also be useful to investigate novel therapies for the treatment and prevention of epilepsy.

Neuropathological spectrum of cortical dysplasia in children with severe focal epilepsies

Abstract: Cortical dysplasias comprise a variable spectrum of clinical, neuroradiological and histopathological findings. We report about a cohort of 25 pediatric patients (mean age 8.1±4.8 years) with severe drug-resistant early onset focal epilepsies (mean duration 2.1±0.4 years), mental/psychomotor retardation, and multilobar epileptogenesis. Compared to age-matched biopsy controls, microscopical inspection of neurosurgically resected specimens revealed dysplastic neurons with/without balloon cells in only 7 patients. According to Palmini’s classification system, these lesions were categorized as focal cortical dysplasia (FCD) type II. All other patients presented with rather subtle but statistically significant neuroanatomical abnormalities. We identified increased numbers of ectopic neurons in white matter and cortical gliosis. However, most intriguing was our finding of a microcolumnar arrangement of cortical neurons in layer III. These microcolumns can be statistically defined as vertical lining of more than eight neurons (two times standard deviation of cell countings obtained from controls). In addition, neuronal perikarya were significantly smaller in epilepsy patients. Although histological abnormalities occurring during postnatal maturation of the brain challenge any neuropathological classification in this group of young patients, we propose that these findings are classified according to FCD type I. Our observations support a concept compatible with regional loss of high-order brain organization.