Barker-Haliski Melissa, DePaula-Silva Ana Beatriz, Pitsch Julika, Sontheimer Harald, Hirsch Lawrence J, Galanopoulou Aristea S, Kearney Jennifer A
Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, WA, USA.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
Epilepsy Curr. 2024 Apr 30:15357597241242238. doi: 10.1177/15357597241242238.
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.
全球约80%的癫痫负担集中在低收入和中等收入国家（LMICs；世界卫生组织，2022年）。尽管有许多治疗癫痫的新疗法，但对现有药物仍有耐药性的患者数量并未改变。此外，尚无疗法在临床上被证明可预防或减轻高危个体癫痫的发生。不幸的是，低收入和中等收入国家获得下一代疗法的机会很低，与癫痫相关的污名仍然很高，获得充足资源的情况也没有改变。因此，全球癫痫负担不成比例地落在低收入和中等收入国家，以至于将全球癫痫风险因素认真纳入临床前研究的策略可能会切实推动21世纪的癫痫治疗。在资源匮乏地区，脑部感染是癫痫的主要风险因素之一。此外，感染和自身免疫相关的脑炎都增加了全球癫痫风险，但相关研究仍相对较少。例如，临床严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染可引发罕见的脑病和急性癫痫发作。在已知会引起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（如自闭症谱系障碍或注意力缺陷多动障碍）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绝佳机会。此外，与病毒感染诱发的脑炎和自身免疫性脑炎相关的趋同神经炎症途径反映了一个尚未开发的治疗机会，有望切实减轻全球癫痫负担。本综述总结了整合脑炎诱发癫痫和癫痫模型的转化研究的最新进展，以及炎症和病毒介导癫痫临床诊断的进展。预计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这种更高认识将对全球癫痫负担产生有益影响。
