title: Pathophysiology of status epilepticus.
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.
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3BG, United Kingdom. Electronic address: m.walker@ucl.ac.uk.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Walker
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology*; D013226:Status Epilepticus / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D017382:Reactive Oxygen Species
keywords: Drug resistance; Excitotoxicity; Mitochondria; Reactive oxygen species; Status epilepticus