Modulation of Immunity and the Inflammatory Response: A New Target for Treating Drug-resistant Epilepsy

Abstract

Until recently, epilepsy medical therapy is usually limited to anti-epileptic drugs (AEDs). However, approximately 1/3 of epilepsy patients, described as drug-resistant epilepsy (DRE) patients, still suffer from continuous frequent seizures despite receiving adequate AEDs treatment of sufficient duration. More recently, with the remarkable progress of immunology, immunity and inflammation are considered to be key elements of the pathobiology of epilepsy. Activation of inflammatory processes in brain tissue has been observed in both experimental seizure animal models and epilepsy patients. Anti-inflammatory and immunotherapies also showed significant anticonvulsant properties both in clinical and in experimental settings. The above emerging evidence indicates that modulation of immunity and inflammatory processes could serve as novel specific targets to achieve potential anticonvulsant effects for the patients with epilepsy, especially DRE. Herein we review the recent evidence supporting the role of inflammation in the development and perpetuation of seizures, and also discuss the recent achievements in modulation of inflammation and immunotherapy applied to the treatment of epilepsy. Apart from medical therapy, we also discuss the influences of surgery, ketogenic diet, and electroconvulsive therapy on immunity and inflammation in DRE patients. Taken together, a promising perspective is suggested for future immunomodulatory therapies in the treatment of patients with DRE.

Epilepsy and the inflammasome: Targeting inflammation as a novel therapeutic strategy for seizure disorders

“…Increased staining for HMGB1, TLR4 and RAGE, is detectable in an analogous pattern to that observed in mouse models of epilepsy in human hippocampal tissue obtained at surgery from patients with (2). Inflammasome formation induces caspase-1 activation (3).…”

Association of Tag SNPs and Rare CNVs of the MIR155HG/miR-155 Gene with Epilepsy in the Chinese Han Population

“…Recent studies have indicated that inflammation probably plays a crucial role in the development of DRE [ 32 – 35 ]. Moreover, inflammatory modulation could improve seizure control in some patients with DRE [ 34 , 35 ], which supports the hypothesis of an inflammatory mechanism of DRE and suggests a new strategy for drug resistance. Interestingly, this study found that the AA genotype at rs4817027 and the CC haplotype (rs987195-rs969885) were genetic susceptibility markers for DRE but the CG haplotype (rs987195-rs969885) was a genetic protective factor against DRE.…”

The efficacy of gastrodin in combination with folate and vitamin B12 on patients with epilepsy after stroke and its effect on HMGB-1, IL-2 and IL-6 serum levels

“…ii) Factors affecting neural cell membrane stability: after stroke, neural cell membrane instability can give rise to abnormalities in the function of surrounding cells and selective neuronal mutations, leading to an increase in neural cell excitability and synchronous discharge, thus resulting in epilepsy ( 9 ). iii) Inflammatory factors: after stroke, long-term inflammatory responses can generate changes in morphology, increasing the amount of neuroglia, thus causing or aggravating epilepsy ( 10 ). iv) Immunological factors: Disorders in immunological functions have been found in EAS patients, including abnormal humoral and cellular immunological functions, which can induce the onset of epilepsy ( 11 ).…”