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

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.

Keywords:

• animal models
• anti-inflammatory treatments
• blood–brain barrier
• comorbidities
• COX-2
• cytokines
• neurodegeneration
• outcome
• prognosis
• refractory status epilepticus
• seizures

Financial & competing interests disclosure

A Vezzani is supported by Fondazione Monzino and EPITARGET (FP7 2007–2013, grant agreement n°602102). 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. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Status epilepticus (SE) is linked to a considerable risk of short-term mortality, unfavorable functional outcome and epilepsy.

• Treatment of SE is essentially based on expert opinions.

• SE etiology and age are the main prognostic determinants.

• Anticonvulsant drug treatment per se seems to have no major impact on SE prognosis. Broad spectrum anti-inflammatory treatments are reserved to patients with a proven autoimmune cause.

• Inflammation appears to play a determinant role in ongoing seizures and their long-term consequences independently of infection or auto-immunity.

• This may lead to reconsideration of the treatment of SE to include adjunctive anti-inflammatory drugs targeted to specific pathogenic pathways.

• Randomized controlled trials are needed in this field.

Notes