Pathophysiology of status epilepticus. (22nd February 2018)

• Record Type: Journal Article
• Authors: Walker, Matthew C.
• Is Part Of: Neuroscience letters. Volume 667(2018)
• Page Start: 84
• Page End: 91
• Publication Date: 2018-02-22
• Subjects: Status epilepticus -- Drug resistance -- Reactive oxygen species -- Mitochondria -- Excitotoxicity; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.12.044
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Mechanisms for the failure of seizure termination are described. Drug resistance of status epilepticus results partly from receptor changes. Status epilepticus can lead to excitotoxic neuronal death. Reactive oxygen species and mitochondrial failure contribute to SE pathology. Abstract: Status epilepticus (SE) is the maximal expression of epilepsy with a high morbidity and mortality. It occurs due to the failure of mechanisms that terminate seizures. Both human and animal data indicate that the longer a seizure lasts, the less likely it is to stop. Recent evidence suggests that there is a critical transition from an ictal to a post-ictal state, associated with a transition from a spatio-temporally desynchronized state to a highly synchronized state, respectively. As SE continues, it becomes progressively resistant to drugs, in particular benzodiazepines due partly to NMDA receptor-dependent internalization of GABA(A) receptors. Moreover, excessive calcium entry into neurons through excessive NMDA receptor activation results in activation of nitric oxide synthase, calpains, and NADPH oxidase. The latter enzyme plays a critical part in the generation of seizure-dependent reactive oxygen species. Calcium also accumulates in mitochondria resulting in mitochondrial failure (decreased ATP production), and opening of the mitochondrial permeability transition pore. Together these changes result in status epilepticus-dependent neuronal death via several pathways. Multiple downstream mechanisms including inflammation, break down of the blood-brain barrier, and changes in gene expression can contribute to later pathological processes including chronic epilepsy and cognitive decline.