Brain on Fire: How Brain Infection and Neuroinflammation Drive Worldwide Epilepsy Burden

IF 5.8 2区 医学 Q1 CLINICAL NEUROLOGY Epilepsy Currents Pub Date : 2024-04-30 DOI:10.1177/15357597241242238
Melissa Barker-Haliski, Ana Beatriz DePaula-Silva, Julika Pitsch, Harald Sontheimer, Lawrence J. Hirsch, Aristea S. Galanopoulou, Jennifer A. Kearney
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Abstract

Roughly 80% of the global burden of epilepsy resides in low- and middle-income countries (LMICs; WHO, 2022). Despite numerous new therapies for the treatment of epilepsy, the number of patients who remain resistant to available medications is unchanged. Additionally, no therapy has yet been clinically proven to prevent or attenuate the development of epilepsy in at-risk individuals. Unfortunately, access to next generation therapies in LMICs is low, the stigma associated with epilepsy remains high, and access to adequate resources is unchanged. Thus, the global epilepsy burden disproportionately falls on LMICs such that strategies to conscientiously integrate global epilepsy risk factors into preclinical research may meaningfully advance 21st century epilepsy therapies. Brain infections are one of the main risk factors for epilepsy in resource-poor settings. Further, both infection- and autoimmune-associated encephalitis contribute to worldwide epilepsy risk and remain relatively understudied. For example, clinical SARS CoV-2 infection can induce rare instances of encephalopathy and acute seizures. Among viruses known to cause acute brain infection, enteroviruses increase risk for encephalitis-induced epilepsy, but are not associated with risk for other neurodevelopmental disorders (eg, autism spectrum or attentional deficit hyperactivity disorders). Naturally occurring models of viral infection-induced epilepsy therefore provide an exquisite opportunity to uncover novel contributors to epileptogenesis. Moreover, the convergent neuroinflammatory pathways that are associated with viral infection-induced encephalitis and autoimmune encephalitis reflect an untapped therapeutic opportunity to meaningfully reduce the global burden of epilepsy. This review summarizes the latest advances in translational research integrating encephalitis-induced seizure and epilepsy models, in tandem with progress in clinical diagnosis of inflammation and virally mediated epilepsy. This improved awareness of the shared biological underpinnings of epileptogenesis following brain infection or autoimmune encephalitis is anticipated to beneficially impact the global burden of epilepsy.
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脑部着火:脑部感染和神经炎症如何导致全球癫痫负担加重
全球约 80% 的癫痫患者生活在中低收入国家(LMICs;WHO,2022 年)。尽管治疗癫痫的新疗法层出不穷,但对现有药物产生抗药性的患者人数却没有变化。此外,还没有任何疗法经临床验证可预防或减轻高危人群癫痫的发展。不幸的是,在低收入和中等收入国家,获得新一代疗法的机会很少,与癫痫相关的耻辱感仍然很高,获得充足资源的机会也没有改变。因此,全球癫痫负担不成比例地落在了低收入和中等收入国家,将全球癫痫风险因素有意识地纳入临床前研究的战略可能会有意义地推动 21 世纪癫痫疗法的发展。在资源匮乏的环境中,脑部感染是癫痫的主要风险因素之一。此外,感染性脑炎和自身免疫相关性脑炎也是导致全球癫痫风险的原因之一,但相关研究仍相对不足。例如,临床 SARS CoV-2 感染可诱发罕见的脑病和急性癫痫发作。在已知可导致急性脑部感染的病毒中,肠道病毒会增加脑炎诱发癫痫的风险,但与其他神经发育障碍(如自闭症谱系或注意缺陷多动障碍)的风险无关。因此,病毒感染诱发癫痫的自然发生模型为揭示癫痫发生的新因素提供了一个绝佳的机会。此外,与病毒感染诱发的脑炎和自身免疫性脑炎相关的神经炎症通路趋同,反映出一种尚未开发的治疗机会,可有效减轻全球癫痫的负担。本综述总结了结合脑炎诱导的癫痫发作和癫痫模型的转化研究的最新进展,以及炎症和病毒介导的癫痫临床诊断的进展。人们对脑部感染或自身免疫性脑炎后癫痫发生的共同生物学基础的认识有所提高,预计这将对全球癫痫负担产生有益影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Epilepsy Currents
Epilepsy Currents CLINICAL NEUROLOGY-
CiteScore
2.40
自引率
5.60%
发文量
88
审稿时长
>12 weeks
期刊介绍: Epilepsy Currents is an open access, bi-monthly current-awareness journal providing reviews, commentaries and abstracts from the world’s literature on the research and treatment of epilepsy. Epilepsy Currents surveys and comments on all important research and developments in a format that is easy to read and reference. Each issue is divided into two main sections: Basic Science and Clinical Science. An outstanding Editorial Board reviews the literature and assigns topics and articles to world experts for comment. In addition, the Editors commission authoritative review articles on important subjects.
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