Epileptogenesis

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

Dynamical intrinsic functional architecture of the brain during absence seizures

Abstract: Epilepsy is characterized by recurrent and temporary brain dysfunction due to discharges of interconnected groups of neurons. The brain of epilepsy patients has a dynamic bifurcation that switches between epileptic and normal states. The dysfunctional state involves large-scale brain networks. It is very important to understand the network mechanisms of seizure initiation, maintenance, and termination in epilepsy. Absence epilepsy provides a unique model for neuroimaging investigation on dynamic evolutions of brain networks over seizure repertoire. By using a dynamic functional connectivity and graph theoretical analyses to study absence seizures (AS), we aimed to obtain transition of network properties that account for seizure onset and offset. We measured resting-state functional magnetic resonance imaging and simultaneous electroencephalography (EEG) from children with AS. We used simultaneous EEG to define the preictal, ictal and postictal intervals of seizures. We measured dynamic connectivity maps of the thalamus network and the default mode network (DMN), as well as functional connectome topologies, during the three different seizure intervals. The analysis of dynamic changes of anti-correlation between the thalamus and the DMN is consistent with an inhibitory effect of seizures on the default mode of brain function, which gradually fades out after seizure onset. Also, we observed complex transitions of functional network topology, implicating adaptive reconfiguration of functional brain networks. In conclusion, our work revealed novel insights into modifications in large-scale functional connectome during AS, which may contribute to a better understanding the network mechanisms of state bifurcations in epileptogenesis.

Epileptogenicity of cortical dysplasia in temporal lobe dual pathology: an electrophysiological study with invasive recordings.

Abstract: Hippocampal sclerosis is often associated with macroscopic or microscopic dysplasia in the temporal neocortex (TN). The relevance of such a dual pathology with regard to epileptogenesis is unclear. This study investigates the role of both pathologies in the generation of ictal and interictal activity. Ictal (113 seizures) and interictal data from invasive EEG recordings with simultaneous depth electrodes in the hippocampus and subdural electrodes over the TN were analysed retrospectively in 12 patients with variable degrees of hippocampal sclerosis and different types of histologically confirmed temporal cortical dysplasia [all male, age at epilepsy onset 25 Hz) and repetitive sharp waves. The interictal patterns over the TN were similar to those seen over extratemporal focal cortical dysplasias. Simultaneous recordings from the hippocampus and the TN strongly suggest that dysplastic tissue in the TN is often epileptogenic. The quantitative contribution of the hippocampus to seizure generation corresponded with the degree of hippocampal pathology, whereas different subtypes of cortical dysplasia did not affect its relative contribution to seizure generation and even mild forms of dysplasia were epileptogenic.

A critical review of mTOR inhibitors and epilepsy: from basic science to clinical trials.

Abstract: Present medications for epilepsy have substantial limitations, such as medical intractability in many patients and lack of antiepileptogenic properties to prevent epilepsy. Drugs with novel mechanisms of action are needed to overcome these limitations. The mTOR signaling pathway has emerged as a possible therapeutic target for epilepsy. Preliminary clinical trials suggest that mTOR inhibitors reduce seizures in tuberous sclerosis complex (TSC) patients with intractable epilepsy. Furthermore, mTOR inhibitors have antiepileptogenic properties in preventing epilepsy in animal models of TSC. Besides TSC, accumulating preclinical data suggest that mTOR inhibitors may have antiseizure or antiepileptogenic actions in other types of epilepsy, including infantile spasms, neonatal hypoxic seizures, absence epilepsy and acquired temporal lobe epilepsy following brain injury, but these effects depend on a number of conditions. Future clinical and basic research is needed to establish whether mTOR inhibitors are an ef...

Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons

Abstract: Epilepsy is a common and refractory neurological disorder, but the neuronal regulatory mechanisms of epileptogenesis remain largely unclear. Activity-dependent transcription of genes for neurotrophins such as brain-derived neurotrophic factor (BDNF) has been shown to promote epileptogenesis; however, little is known about factors that may act as intrinsic, homeostatic or counterbalancing mechanisms. Using rodent models, here we show that limbic seizure activity upregulated NRG1-ErbB4 signaling and that epileptogenesis was inhibited by infusing NRG1 intracerebrally but exacerbated by neutralizing endogenous NRG1 with soluble ErbB4 extracellular domain, by inhibiting ErbB4 activation or by deleting the Erbb4 gene. Furthermore, specific depletion of ErbB4 in parvalbumin-expressing interneurons abolished NRG1-mediated inhibition of epileptogenesis and promoted kindling progression, resulting in increased spontaneous seizures and exuberant mossy fiber sprouting. In contrast, depleting ErbB4 in CaMKII alpha-positive pyramidal neurons had no effect. Thus, NRG1-induced activation of ErbB4 in parvalbumin-expressing inhibitory interneurons may serve as a critical endogenous negative-feedback mechanism to suppress limbic epileptogenesis.