Predicting epilepsy in cerebral malaria: working toward identifying biomarkers of epileptogenesis in children

项目摘要/摘要 每年有50多万儿童患有脑型疟疾，占总人口的10%-16%。 在两年内患上癫痫。因此，脑型疟疾对全球癫痫起着重要作用。 负担。就像许多获得性癫痫一样，在如何识别的知识上仍然存在着重要的差距。 哪些儿童感染脑型疟疾后会有癫痫发作的风险。身份识别 预示癫痫风险的生物标志物将有助于及时识别谁将从CLOSE中获得最大好处 临床监测--改善有限可用资源分配的关键考虑因素 这种疾病最流行的地区。 确定特定的临床和脑电(EEG)指标，这些指标赋予后遗症的风险 疟疾癫痫也将有助于了解癫痫在这种疾病中的发展。研究这些 获得性癫痫的过程被证明是困难的，因为病因和 脑损伤后癫痫发生的时间。脑型疟疾有可能成为一种独特的治疗模式 癫痫发生生物标志物的鉴定，因为它是一种癫痫后高发病率的单一疾病状态 在相对较短的时间内发展。这项提议将解决知识方面的主要差距。 关于在资源有限的环境中随时可用的临床和EEG指标的实用性，以用于预测 预测脑型疟疾儿童癫痫风险的能力。这些发现有可能为 为未来针对减少脑后疟疾的有针对性干预措施的研究奠定基础 癫痫的发展。 这份以患者为导向的导师职业发展奖申请符合以下两个基准 由国家神经紊乱和中风研究所和美国癫痫学会设定，包括 区域II-了解癫痫的发生，区域III-识别生物标记物。这项提议还旨在 为应聘者的培训和职业发展提供重要机会。帕特尔医生已经 在全球神经学研究和临床神经生理学方面的经验；这一奖项将使她获得 在脑电计算分析方面的临床研究方法和具体培训方面的进一步经验。 这些技能将为进一步研究这种情况以及可能在抗癫痫发生方面奠定基础。 脑后疟疾癫痫模型的试验。最终，这项研究提案和随附的 培训将为成功的独立研究职业生涯提供坚实的基础 了解癫痫的发生，降低全球儿童获得性癫痫的风险。

PROJECT SUMMARY/ABSTRACT Over half a million children suffer from cerebral malaria annually, with up to 10-16% of this population developing epilepsy within two years. Thus, cerebral malaria contributes significantly to the global epilepsy burden. As in many acquired epilepsies, there remains an important gap in knowledge on how to identify which children after cerebral malaria infection will be at risk for epilepsy development. Identification of biomarkers heralding epilepsy risk would improve timely identification of who would most benefit from closer clinical monitoring- a critical consideration for improved allocation of the limited available resources in regions where this disease is most prevalent. Identification of the specific clinical and electroencephalographic (EEG) metrics which confer risk of post- malaria epilepsy will also importantly help understand epilepsy development in this disease. Studying these processes in acquired epilepsies has proven difficult to date due to the varied nature of etiologies and timing of epilepsy development after brain insult. Cerebral malaria has potential to be a unique model for identification of epileptogenesis biomarkers, as it is a single disease state with a high rate of post-epilepsy development within a relatively short time frame. This proposal will address key gaps in knowledge regarding the utility of clinical and EEG metrics readily available in resource-limited settings for predictive ability to prognosticate epilepsy risk in children with cerebral malaria. The findings have the potential to lay the foundation for future research of targeted interventions directed toward reducing post-cerebral malaria epilepsy development. This Mentored Patient-Oriented Career Development Award application aligns with two of the benchmarks set by the National Institute of Neurological Disorders and Stroke and American Epilepsy Society, including Area II- understanding epileptogenesis, and Area III- identify biomarkers. This proposal is also designed to provide important opportunities for the training and career development of the candidate. Dr. Patel has experience in global neurology research and clinical neurophysiology; this award will allow her to gain further experience in clinical research methodology and specific training in computational analysis of EEG. These skills will lay a foundation for further study of this condition and potentially in anti-epileptogenesis trials of the post-cerebral malaria epilepsy model. Ultimately, this research proposal and the accompanying training will provide a strong foundation for a successful independent research career devoted to the understanding of epileptogenesis and reducing the risk of acquired epilepsies in children globally.