Identifying biomarkers for epilepsy after cerebral malaria in Zambian children: rationale and design of a prospective observational study.
Identifying biomarkers for epilepsy after cerebral malaria in Zambian children: rationale and design of a prospective observational study.
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DOI：
10.1136/bmjopen-2022-062948
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发表时间：
2022-07-18
期刊：
影响因子：
2.9
通讯作者：
Rotenberg, Alexander
中科院分区：
文献类型：
--
作者：
Patel, Archana A.;Birbeck, Gretchen L.;Mazumdar, Maitreyi;Mwanza, Suzanna;Nyirongo, Rosemary;Berejena, Dixon;Kasolo, Joseph;Mwale, Tina;Nambeye, Violet;Nkole, Kafula Lisa;Kawatu, Nfwama;Zhang, Bo;Rotenberg, Alexander
影响中枢神经系统（CM）的疟疾是资源匮乏环境中儿科癫痫的主要原因，10%-16%的幸存者在感染后2年内患上癫痫。尽管疟疾后癫痫（PME）的风险很高，但缺乏指示哪些CM幸存者将发展癫痫的生物标志物。这些生物标志物对于识别那些可能从密切监测和/或预防性治疗中获益最多的高危人群至关重要。脑电图（EEG）包含信号（特别是伽马频率活动），这些信号与PME的高风险相关，并为癫痫的发展提供了生物标志物。我们建议研究定量和定性EEG指标在预测PME中的敏感性，以及该措施与其他临床指标的潜在敏感性增加。我们的目标是开发一种由EEG和临床病史指标组成的预测性PME指数，这些指标在低资源地区非常可行。这项在赞比亚东部进行的前瞻性观察性研究将招募250名年龄在6个月至11岁之间的急性CM儿童，并对他们进行为期两年的随访。将排除既存癫痫诊断的儿童。结局指标将包括常规EEG记录的定性和定量分析，以及急性和亚急性期的临床指标，包括寄生虫负荷的富组氨酸蛋白2水平、昏迷深度和持续时间、急性癫痫发作的存在和严重程度、低血糖的存在、最高体温和CM后1个月的神经发育评估评分。我们将通过多变量逻辑回归分析测试这些EEG和临床指标在预测癫痫发展中的性能。本研究已获得波士顿儿童医院机构审查委员会、赞比亚大学生物医学研究伦理委员会和赞比亚国家卫生研究局的批准。研究结果将在赞比亚当地传播，然后在可行的情况下在国际、开放获取、同行评审的期刊上发表。
Malaria affecting the central nervous system (CM) is a major contributor to paediatric epilepsy in resource-poor settings, with 10%–16% of survivors developing epilepsy within 2 years of infection. Despite high risk for post-malaria epilepsy (PME), biomarkers indicating which CM survivors will develop epilepsy are absent. Such biomarkers are essential to identify those at highest risk who might benefit most from close surveillance and/or preventive treatments. Electroencephalography (EEG) contains signals (specifically gamma frequency activity), which are correlated with higher risk of PME and provide a biomarker for the development of epilepsy. We propose to study the sensitivity of quantitative and qualitative EEG metrics in predicting PME, and the potential increased sensitivity of this measure with additional clinical metrics. Our goal is to develop a predictive PME index composed of EEG and clinical history metrics that are highly feasible to obtain in low-resourced regions. This prospective observational study being conducted in Eastern Zambia will recruit 250 children aged 6 months to 11 years presenting with acute CM and follow them for two years. Children with pre-existing epilepsy diagnoses will be excluded. Outcome measures will include qualitative and quantitative analysis of routine EEG recordings, as well as clinical metrics in the acute and subacute period, including histidine-rich protein 2 levels of parasite burden, depth and length of coma, presence and severity of acute seizures, presence of hypoglycaemia, maximum temperature and 1-month post-CM neurodevelopmental assessment scores. We will test the performance of these EEG and clinical metrics in predicting development of epilepsy through multivariate logistic regression analyses. This study has been approved by the Boston Children’s Hospital Institutional Review Board, University of Zambia Biomedical Research Ethics Committee, and National Health Research Authority of Zambia. Results will be disseminated locally in Zambia followed by publication in international, open access, peer-reviewed journals when feasible.
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影响因子：
11.2
作者：
Kotulska K;Kwiatkowski DJ;Curatolo P;Weschke B;Riney K;Jansen F;Feucht M;Krsek P;Nabbout R;Jansen AC;Wojdan K;Sijko K;Głowacka-Walas J;Borkowska J;Sadowski K;Domańska-Pakieła D;Moavero R;Hertzberg C;Hulshof H;Scholl T;Benova B;Aronica E;de Ridder J;Lagae L;Jóźwiak S;EPISTOP Investigators
通讯作者：
EPISTOP Investigators
影响因子：
48
作者：
Birbeck, Gretchen L.;Molyneux, Malcolm E.;Taylor, Terrie E.
通讯作者：
Taylor, Terrie E.
影响因子：
2.2
作者：
Banerjee, Poonam Nina;Filippi, David;Hauser, W. Allen
通讯作者：
Hauser, W. Allen
影响因子：
3.7
作者：
MacMullin, Paul;Hodgson, Nathaniel;Rotenberg, Alexander
通讯作者：
Rotenberg, Alexander
影响因子：
5.2
作者：
Kakooza-Mwesige, Angelina;Ssebyala, Keron;Grether, Judith K.
通讯作者：
Grether, Judith K.