title: Mechanistic and pharmacologic aspects of status epilepticus and its treatment with new antiepileptic drugs.
abstract: We review recent advances in our understanding and treatment of status epilepticus (SE). Repeated seizures cause an internalization of gamma-aminobutyric acid (GABA)(A) receptors, together with a movement of N-methyl-d-aspartate (NMDA) receptors to the synapse. As a result, the response of experimental SE to treatment with GABAergic drugs (but not with NMDA antagonists) fades with increasing seizure duration. Prehospital treatment, which acts before these changes are established, is finding increased acceptance, and solid evidence of its efficacy is available, particularly in children. Rational polypharmacy aims at multiple receptors or ion channels to increase inhibition and simultaneously reduce excitation. Combining GABA(A) agonists with NMDA antagonists and with agents acting at other sites is successful in treating experimental SE, and in reducing SE-induced brain damage and epileptogenesis. The relevance of these experimental data to clinical SE is actively debated. Valproate and levetiracetam have recently become available for intravenous use, and the use of ketamine and of other agents (topiramate, felbamate, etc.) have seen renewed interest. A rapidly increasing but largely anecdotal body of literature reports success in seizure control at the price of relatively few complications with the clinical use of those agents in refractory SE.
authors.affiliation: Epilepsy Research Laboratories, Department of Neurology, David Gefen School of Medicine at UCLA, Los Angeles, California, USA. wasterla@ucla.edu
authors.forename: Claude G
authors.initials: CG
authors.lastname: Wasterlain
authors.forename: James W Y
authors.initials: JW
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D013226:Status Epilepticus / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents