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

预测脑型疟疾中的癫痫：致力于识别儿童癫痫发生的生物标志物

• 批准号: 10662476
• 负责人: Archana A. Patel
• 金额: $ 22.88万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662476
• 关键词: Acute; Affect; Africa; American; Antiepileptogenic; Area; Asphyxia Neonatorum; Award; Benchmarking; Biological; Biological Markers; Brain; Cerebral Malaria; Characteristics; Child; Childhood; Classification; Clinical; Clinical Data; Clinical Research; Clinical Trials Design; Coma; Complex; Computer Analysis; Development; Disease; Electroencephalography; Enrollment; Epilepsy; Epileptogenesis; Etiology; Fever; Foundations; Frequencies; Future; Goals; Hospitalization; Hypoglycemia; Individual; Infection; International; Intervention; K-Series Research Career Programs; Knowledge; Malaria; Measures; Mentors; Modeling; Monitor; Motor; National Institute of Neurological Disorders and Stroke; Nature; Neurologic Dysfunctions; Neurology; Outcome; Parasites; Participant; Patients; Phase; Population; Predictive Value; Process; Publishing; Questionnaires; Recording of previous events; Recovery; Regional Disease; Research; Research Methodology; Research Proposals; Resource Allocation; Resource-limited setting; Resources; Risk; Risk Factors; Risk Reduction; Seizures; Severities; Severity of illness; Societies; Statistical Methods; Survivors; System; Targeted Research; Testing; Time; Training; Translating; Visual; Zambia; acquired epilepsy; biomarker identification; career; career development; childhood epilepsy; clinical risk; cohort; cost; design; diagnostic criteria; epileptiform; experience; experimental study; follow-up; improved; interest; machine learning algorithm; malaria infection; motor impairment; neurodevelopment; neurophysiology; patient oriented; potential biomarker; preclinical study; predictive modeling; prevent; prognostication; prospective; response; risk prediction; skills; supervised learning; training opportunity; trend

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.

项目总结/摘要 每年有50多万儿童患有脑型疟疾，占总人口的10- 16 两年内患上癫痫因此，脑型疟疾是全球癫痫的重要原因之一。 负担在许多获得性癫痫，仍然有一个重要的知识差距，如何识别 脑型疟疾感染后的儿童将有癫痫发展的风险。鉴定 预示癫痫风险的生物标志物将有助于及时识别谁将最受益于更密切的 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。 识别特定的临床和脑电图（EEG）指标，这些指标会导致术后 疟疾癫痫也将有助于了解这种疾病的癫痫发展。研究这些 由于病因的不同性质， 脑损伤后癫痫发展的时间。脑型疟疾有可能成为一种独特的模型， 癫痫发生生物标志物的鉴定，因为它是一种癫痫后发病率高的单一疾病状态 在相对较短的时间内发展。该提案将解决知识方面的主要差距 关于在资源有限的环境中容易获得的临床和EEG指标的实用性， 预测脑型疟疾患儿癫痫风险的能力这些发现有可能奠定 未来研究针对减少脑后疟疾的有针对性的干预措施的基础 癫痫发展 这个指导病人为导向的职业发展奖申请符合两个基准 由美国国家神经疾病和中风研究所和美国癫痫协会制定，包括 区域II-了解癫痫发生，区域III-确定生物标志物。该提案还旨在 为候选人的培训和职业发展提供重要机会。帕特尔医生 在全球神经病学研究和临床神经生理学方面的经验;该奖项将使她获得 在临床研究方法学方面有进一步的经验，并接受过EEG计算分析方面的专门培训。 这些技术将为进一步研究这种情况和潜在的抗癫痫作用奠定基础 脑疟疾后癫痫模型的试验。最终，这项研究提案和伴随的 培训将提供一个成功的独立的研究生涯致力于一个坚实的基础， 了解癫痫发生和降低全球儿童获得性癫痫的风险。

项目成果

Protocol for a magnetic resonance imaging study of participants in the fever RCT: Does fever control prevent brain injury in malaria?

• DOI: 10.1371/journal.pone.0294823
• 发表时间: 2024-04-19
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Chilombe，Moses B.;Seydel，Karl B.;Birbeck，Gretchen L.
• 通讯作者: Birbeck，Gretchen L.