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. Keywords: Immunity, Inflammation, Drug-Resistant Epilepsy, Auto-antibodies, Cytokines
Highlights
Affecting around 50 million people worldwide, epilepsy is a most common disabling neurological disorder, which is characterized by recurring unprovoked seizures [1]
Inflammation in the brain is usually caused by an precipitate injurious stimulus of peripheral neurons and results in the release of cytokines and neuropeptides with a variety of cytological and chemical reactions, which further affect the brain vascular permeability and help initiate five major mechanisms of drug-resistant epilepsy (DRE)
Modoni A. et al [75] reported a case of acute nonherpetic LE with negative testing for antibodies directed against onconeuronal and cell membrane antigens, including VGKCs and NMDAR, that showed a dramatic response to treatment with intravenous immunoglobulin (IVIG) followed by a short course of oral prednisone, obtaining a full clinical recovery
Summary
Affecting around 50 million people worldwide, epilepsy is a most common disabling neurological disorder, which is characterized by recurring unprovoked seizures [1]. Even the first non-folk medication of epilepsy, potassium bromide, has been introduced for oneand-a-half century [3, 4], and the introduction of over 10 new-generation anti-epileptic drugs (AEDs) in the last decades, the currently available AEDs still only provide a satisfactory level of seizure control in up to 70% of patients with epilepsy [5, 6]. Uncontrolled seizures are occurred in nearly 1/3 of adult epilepsy patients, which are defined as drug-resistant epilepsy (DRE) [7]. Modulation of Immunity and Inflammatory Response summarize the current approaches of immunomodulation and anti-inflammatory therapy in the treatment of DRE; and iii) analyze the benefits and side effects of these treatments, and to discuss the future directions
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