Immunity and inflammation in status epilepticus and its sequelae: possibilities for therapeutic application

• Type of Material: Article
• Authors: Annamaria Vezzani, Mario Negri Institute for Pharmacological Research; Raymond Dingledine, Emory University; Andrea O Rossetti, University of Lausanne
• Language: English
• Date: 2015-01-01
• Publisher: Expert Reviews (formerly Future Drugs)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Informa UK, Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1586/14737175.2015.1079130
• Title of Journal or Parent Work: Expert Review of Neurotherapeutics
• ISSN: 1473-7175
• Volume: 15
• Issue: 9
• Start Page: 1081
• End Page: 1092
• Grant/Funding Information: A Vezzani is supported by Fondazione Monzino and EPITARGET (FP7 2007–2013, grant agreement no602102).; R Dingledine is supported by National Institute of Neurological Disorders and Stroke (NINDS) CounterACT program grant U01 NS05158 and NIH grants R21 NS074169 and P20 NS080185.
• Keywords: neurodegeneration; RAT MODEL; Pharmacology & Pharmacy; animal models; prognosis; Clinical Neurology; COX-2; TEMPORAL-LOBE EPILEPSY; REFRACTORY STATUS EPILEPTICUS; EXPERIMENTAL FEBRILE SEIZURES; refractory status epilepticus; blood-brain barrier; BRAIN INFLAMMATION; Neurosciences & Neurology; RETROSPECTIVE MULTICENTER; comorbidities; Science & Technology; outcome; PROSTAGLANDIN RECEPTOR EP2; seizures; Life Sciences & Biomedicine; SPONTANEOUS RECURRENT SEIZURES; MEDIATED STATUS EPILEPTICUS; cytokines; anti-inflammatory treatments; MOBILITY GROUP BOX-1
• Research Categories: Health Sciences, General; Health Sciences, Pharmacology; Biology, Neuroscience

Abstract

Status epilepticus (SE) is a life-threatening neurological emergency often refractory to available treatment options. It is a very heterogeneous condition in terms of clinical presentation and causes, which besides genetic, vascular and other structural causes also include CNS or severe systemic infections, sudden withdrawal from benzodiazepines or anticonvulsants and rare autoimmune etiologies. Treatment of SE is essentially based on expert opinions and antiepileptic drug treatment per se seems to have no major impact on prognosis. There is, therefore, urgent need of novel therapies that rely upon a better understanding of the basic mechanisms underlying this clinical condition. Accumulating evidence in animal models highlights that inflammation ensuing in the brain during SE may play a determinant role in ongoing seizures and their long-term detrimental consequences, independent of an infection or auto-immune cause; this evidence encourages reconsideration of the treatment flow in SE patients.