Edridge Arthur W D, Abd-Elfarag Gasim, Deijs Martin, Broeks Melissa H, Cristella Cosimo, Sie Brandon, Vaz Frédéric M, Jans Judith J M, Calis Job, Verhoef Hans, Demir Ayse, Poppert Sven, Nickel Beatrice, van Dam Alje, Sebit Boy, Titulaer Maarten J, Verweij Jaco J, de Jong Menno D, van Gool Tom, Faragher Brian, Verhoeven-Duif Nanda M, Elledge Stephen J, van der Hoek Lia, Boele van Hensbroek Michael
Amsterdam Centre for Global Child Health, Emma Children's Hospital, Amsterdam UMC, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Brain Commun. 2023 Aug 17;5(5):fcad223. doi: 10.1093/braincomms/fcad223. eCollection 2023.
Nodding syndrome is a neglected, disabling and potentially fatal epileptic disorder of unknown aetiology affecting thousands of individuals mostly confined to Eastern sub-Saharan Africa. Previous studies have identified multiple associations-including , antileiomodin-1 antibodies, vitamin B deficiency and measles virus infection-yet, none is proven causal. We conducted a case-control study of children with early-stage nodding syndrome (symptom onset <1 year). Cases and controls were identified through a household survey in the Greater Mundri area in South Sudan. A wide range of parasitic, bacterial, viral, immune-mediated, metabolic and nutritional risk factors was investigated using conventional and state-of-the-art untargeted assays. Associations were examined by multiple logistic regression analysis, and a hypothetical causal model was constructed using structural equation modelling. Of 607 children with nodding syndrome, 72 with early-stage disease were included as cases and matched to 65 household- and 44 community controls. infection (odds ratio 7.04, 95% confidence interval 2.28-21.7), infection (odds ratio 2.33, 95% confidence interval 1.02-5.3), higher antimalarial seroreactivity (odds ratio 1.75, 95% confidence interval 1.20-2.57), higher vitamin E concentration (odds ratio 1.53 per standard deviation increase, 95% confidence interval 1.07-2.19) and lower vitamin B concentration (odds ratio 0.56 per standard deviation increase, 95% confidence interval 0.36-0.87) were associated with higher odds of nodding syndrome. In a structural equation model, we hypothesized that infection, higher vitamin E concentration and fewer viral exposures increased the risk of nodding syndrome while lower vitamin B concentration, and malaria infections resulted from having nodding syndrome. We found no evidence that antileiomodin-1 antibodies, vitamin B and other factors were associated with nodding syndrome. Our results argue against several previous causal hypotheses including . Instead, nodding syndrome may be caused by a complex interplay between multiple pathogens and nutrient levels. Further studies need to confirm these associations and determine the direction of effect.
点头综合征是一种被忽视的、致残且可能致命的癫痫疾病，病因不明，影响着数千人，主要集中在撒哈拉以南非洲东部地区。先前的研究已经确定了多种关联，包括抗雷莫丁 -1 抗体、维生素 B 缺乏和麻疹病毒感染，但尚无一种被证实具有因果关系。我们对早期点头综合征（症状发作 <1 年）的儿童进行了一项病例对照研究。通过在南苏丹大蒙德里地区的家庭调查确定病例和对照。使用传统和最先进的非靶向检测方法对广泛的寄生虫、细菌、病毒、免疫介导、代谢和营养风险因素进行了调查。通过多元逻辑回归分析检验关联，并使用结构方程模型构建了一个假设的因果模型。在 607 名点头综合征儿童中，72 名早期疾病儿童被纳入病例组，并与 65 名家庭对照和 44 名社区对照进行匹配。感染（比值比 7.04，95% 置信区间 2.28 - 21.7）、感染（比值比 2.33，95% 置信区间 1.02 - 5.3）、较高的抗疟疾血清反应性（比值比 1.75，95% 置信区间 1.20 - 2.57）、较高的维生素 E 浓度（每标准差增加比值比 1.53，95% 置信区间 1.07 - 2.19）和较低的维生素 B 浓度（每标准差增加比值比 0.56，95% 置信区间 0.36 - 0.87）与点头综合征的较高几率相关。在一个结构方程模型中，我们假设感染、较高的维生素 E 浓度和较少的病毒暴露增加了点头综合征的风险，而较低的维生素 B 浓度、和疟疾感染是由点头综合征导致的。我们没有发现证据表明抗雷莫丁 -1 抗体、维生素 B 和其他因素与点头综合征有关。我们的结果反驳了之前的几个因果假设，包括 。相反，点头综合征可能是由多种病原体和营养水平之间的复杂相互作用引起的。需要进一步的研究来证实这些关联并确定影响方向。
