Epileptogenesis

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

Preventing and treating posttraumatic seizures: the human experience.

Abstract: Posttraumatic epilepsy presents an ideal target for prevention efforts. Traumatic brain injury (TBI) is common, characteristics that put people at high risk such as penetrating injury or subdural hematoma or provoked seizures are easily identified, and the latency between the injury and the onset of epileptic seizures is frequently short. Several drugs have been tested for their ability to prevent provoked seizures and epilepsy after TBI. We describe the design of those studies and their results. Phenytoin and carbamazepine significantly reduce the incidence of provoked seizures. Phenobarbital and the combination of phenobarbital and phenytoin also look promising for reducing provoked seizures, but small sample sizes in the studies evaluating these drugs do not allow definitive conclusions. None of the drugs studied (phenytoin, phenobarbital, their combination, carbamazepine, valproate, or magnesium) have shown reliable evidence that they prevent, or even suppress, epileptic seizures after TBI. For most of the regimens tested (the phenytoin/phenobarbital combination being the exception), the best estimate of effect is under a 25% reduction in posttraumatic seizures, well less than the 50% reduction most studies were designed to detect. The evaluation of the tested drugs has serious limitations, however, and antiepileptic drugs (AEDs) developed since 1980 and other compounds have barely been tested at all. Better understanding the process of epileptogenesis, testing treatments that demonstrate antiepileptogenic effects in the laboratory, and performing thorough preclinical and phase II evaluations before attempting definitive trials should greatly improve the chance of identifying ways to prevent posttraumatic epilepsy, providing the ultimate cure for this condition.

Selective Alterations in GABAA Receptor Subtypes in Human Temporal Lobe Epilepsy

Abstract: Temporal lobe epilepsy (TLE) is associated with impaired inhibitory neurotransmission. Studies in animal models suggest that GABA(A) receptor dysfunction contributes to epileptogenesis. To understand the mechanisms underlying TLE in humans, it is fundamental to determine whether and how GABA(A) receptor subtypes are altered. Furthermore, identifying novel receptor targets is a prerequisite for developing selective antiepileptic drugs. We have therefore analyzed subunit composition and distribution of the three major GABA(A) receptor subtypes immunohistochemically with subunit-specific antibodies (alpha1, alpha2, alpha3, beta2,3, and gamma2) in surgical specimens from TLE patients with hippocampal sclerosis (n = 16). Profound alterations in GABA(A) receptor subtype expression were observed when compared with control hippocampi (n = 10). Although decreased GABA(A) receptor subunit staining, reflecting cell loss, was observed in CA1, CA3, and hilus, the distinct neuron-specific expression pattern of the alpha-subunit variants observed in controls was markedly changed in surviving neurons. In granule cells, prominent upregulation mainly of the alpha2-subunit was seen on somata and apical dendrites with reduced labeling on basal dendrites. In CA2, differential rearrangement of all three alpha-subunits occurred. Moreover, there was layer-specific loss of alpha1-subunit-immunoreactive interneurons in hippocampus proper, whereas surviving interneurons exhibited extensive changes in dendritic morphology. Throughout, expression patterns of beta2,3- and gamma2-subunits largely followed those of alpha-subunit variants. These results demonstrate unique subtype-specific expression of GABA(A) receptors in human hippocampus. The significant reorganization of distinct receptor subtypes in surviving hippocampal neurons of TLE patients with hippocampal sclerosis underlines the potential for synaptic plasticity in the human GABA system.

Epilepsy after head injury: an overview.

Abstract: Traumatic brain injury (TBI) has been recognized as a cause of epilepsy since antiquity, and it remains one of the most common and important causes of acquired epilepsy today. Epidemiologic studies have demonstrated a clear relationship between the severity of injury and the likelihood of developing epilepsy, with the risk approaching 50% in TBI cases associated with direct injury to brain parenchyma. Importantly, many TBI victims develop epilepsy months or years following the initial injury, making this patient population a prime target for the development of antiepileptogenesis therapies. However, progress in this area of clinical research is hindered by the lack of reliable and valid biomarkers. Given current events in the Middle East and elsewhere, the importance of TBI and epilepsy deserves special attention due to the increase in severe head trauma associated with modern warfare.