Epileptogenesis

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

Responses to single pulse electrical stimulation identify epileptogenesis in the human brain in vivo.

Abstract: The aim of the present study was to investigate in vivo cortical excitability in the human brain. We studied 45 consecutive patients with refractory epilepsy in whom subdural or intracerebral electrodes were implanted for assessment prior to epilepsy surgery. We compared cortical responses to single pulse stimulation (up to 8 mA, 1 ms duration) in areas where seizure onset occurred, with responses recorded elsewhere. Two main types of responses were seen: (i) 'early responses', spikes and/or slow waves starting within 100 ms after the stimulus which were observed in most regions in all patients; and (ii) 'delayed responses', spikes or sharp waves occurring between 100 ms and 1 s after stimulation which were seen in some regions in 27 patients. The distributions of early and delayed responses were compared with the topography of seizure onset. Whereas early responses were seen in most regions and seem to be a normal response of the cortex to single pulse stimulation, the distributions of delayed responses were significantly associated with the regions where seizure onset occurred. We conclude that the presence of delayed responses can identify regions of hyperexcitable cortex in the human brain. The study of delayed responses may improve our understanding of the physiology and dynamics of neuronal circuits in epileptic tissue and may have an immediate clinical application in assessment of candidates for surgical treatment of epilepsy.

Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. I. Development of seizurelike activity in low extracellular calcium.

Abstract: Epileptiform activity induced in rat hippocampal slices by lowering extracellular Ca2+ concentration ([Ca2+]o) was studied with extracellular and intracellular recordings. Perfusing the slices with...

Alterations of hippocampal GABAergic system contribute to development of spontaneous recurrent seizures in the rat lithium-pilocarpine model of temporal lobe epilepsy

Abstract: Reorganization of excitatory and inhibitory circuits in the hippocampal formation following seizure-induced neuronal loss has been proposed to underlie the development of chronic seizures in temporal lobe epilepsy (TLE). Here, we investigated whether specific morphological alterations of the GABAergic system can be related to the onset of spontaneous recurrent seizures (SRS) in the rat lithium-pilocarpine model of TLE. Immunohistochemical staining for markers of interneurons and their projections, including parvalbumin (PV), calretinin (CR), calbindin (CB), glutamic acid decarboxylase (GAD), and type 1 GABA transporter (GAT1), was performed in brain sections of rats treated with lithium-pilocarpine and sacrificed after 24 h, during the silent phase (6 and 12 days), or after the onset of SRS (10-18 days after treatment). Semiquantitative analysis revealed a selective loss of interneurons in the stratum oriens of CA1, associated with a reduction of GAT1 staining in the stratum radiatum and stratum oriens. In contrast, interneurons in CA3 were largely preserved, although GAT1 staining was also reduced. These changes occurred within 6 days after treatment and were therefore insufficient to cause SRS. In the dentate gyrus, extensive cell loss occurred in the hilus. The pericellular innervation of granule cells by PV-positive axons was markedly reduced, although the loss of PV-interneurons was only partial. Most strikingly, the density of GABAergic axons, positive for both GAD and GAT1, was dramatically increased in the inner molecular layer. This change emerged during the silent period, but was most marked in animals with SRS. Finally, supernumerary CB-positive neurons were detected in the hilus, selectively in rats with SRS. These findings suggest that alterations of GABAergic circuits occur early after lithium-pilocarpine-induced status epilepticus and contribute to epileptogenesis. In particular, the reorganization of GABAergic axons in the dentate gyrus might contribute to synchronize hyperexcitability induced by the interneuron loss during the silent period, leading to the onset of chronic seizures.

Interictal spikes and epileptogenesis.

Abstract: Interictal spikes are widely accepted diagnostically as a sign of epilepsy, but reasons for the presence of interictal activity in the epileptic brain are unknown. Interictal spikes are easily generated in normal brain by pharmacologically reducing inhibition, and experimental studies of acquired epilepsy indicate that spikes precede seizures. These data lead to the hypothesis that interictal spikes are correlated with epilepsy because they play a fundamental role in epileptogenesis following brain injury. Spikes may guide sprouting axons back to their network of origin, increase and sustain the strength of the synapses formed by sprouted axons, and alter the balance of ion channels in the epileptic focus, such that seizures become possible. This hypothesis has implications that are testable: altering spiking or the calcium signals generated by spikes should alter epileptogenesis and spikes should precede seizures in brain-injured human patients.