Pathophysiology of status epilepticus.
The cellular and molecular pathophysiology of status epilepticus (SE) provides a conceptual framework for understanding clinical scenarios and prospectively designing logical therapies. SE is a dynamic process that evolves over time in a predictable manner with an established sequence of EEG, motor, physiologic, and cellular changes. Neuronal injury and death are the result of processes intrinsic to the brain, mediated by a complex neurotoxic cascade consisting of multiple serial and parallel processes. The risk of cell injury depends also on the overall pathophysiologic profile, including the presence of alterations resulting from SE and occurring independent of SE. On neurophysiologic grounds, we divide SE into "spike-wave" and "nonspike-wave" forms. Spike-wave "absence" status epilepticus carries a low risk of epileptic brain damage, and therapy should be adjusted accordingly. All nonspike-wave SE has a theoretical basis for epileptic brain damage, but the actual risk is variable. There is a significant known risk of cell injury during generalized convulsive SE, a variety of nonspike-wave SE, so aggressive treatment is warranted to prevent sequelae. There is also a theoretical basis for epileptic brain damage in nonspike-wave nonconvulsive SE, but prospective studies are needed to determine which of these patients warrant aggressive therapy. Based on pathophysiologic principles, future treatment of nonspike-wave SE may use a combination of anti-ictal agents, including gamma-aminobutyric acid agonists and N-methyl-D-aspartate antagonists, as well as various neuroprotectants.
Fountain
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NB
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Lothman
E W
EW
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D013226:Status Epilepticus / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology
D018377:Neurotransmitter Agents