Makerere University College of Health Sciences, Kampala, Uganda.
Centre of Tropical Neuroscience (CTN), Kitgum Site, Uganda.
Epilepsia Open. 2021 Jun;6(2):297-309. doi: 10.1002/epi4.12463. Epub 2021 Mar 12.
Nodding syndrome is a poorly understood epileptic encephalopathy characterized by a unique seizure type-head nodding-and associated with Onchocerca volvulus infection. We hypothesized that altered immune activation in the cerebrospinal fluid (CSF) and plasma of children with nodding syndrome may yield insights into the pathophysiology and progression of this seizure disorder.
We conducted a case-control study of 154 children (8 years or older) with long-standing nodding syndrome and 154 healthy age-matched community controls in 3 districts of northern Uganda affected by nodding syndrome. Control CSF samples were obtained from Ugandan children in remission from hematological malignancy during routine follow-up. Markers of immune activation and inflammation (cytokines and chemokines) and complement activation (C5a) were measured in plasma and CSF using ELISA or Multiplex Luminex assays. O volvulus infection was assessed by serology for anti-OV-16 IgG levels.
The mean (SD) age of the population was 15.1 (SD: 1.9) years, and the mean duration of nodding syndrome from diagnosis to enrollment was 8.3 (SD: 2.7) years. The majority with nodding syndrome had been exposed to O volvulus (147/154 (95.4%)) compared with community children (86/154 (55.8%)), with an OR of 17.04 (95% CI: 7.33, 45.58), P < .001. C5a was elevated in CSF of children with nodding syndrome compared to controls (P < .0001). The levels of other CSF markers tested were comparable between cases and controls after adjusting for multiple comparisons. Children with nodding syndrome had lower plasma levels of IL-10, APRIL, CCL5 (RANTES), CCL2, CXCL13, and MMP-9 compared with community controls (P < .05 for all; multiple comparisons). Plasma CRP was elevated in children with nodding syndrome compared to community children and correlated with disease severity.
Nodding syndrome is associated with exposure to O. volvulus. Compared to controls, children with long-standing symptoms of nodding syndrome show evidence of complement activation in CSF and altered immune activation in plasma.
点头综合征是一种病因尚未完全阐明的癫痫性脑病，其特征为独特的发作类型——点头，并与旋盘尾丝虫感染有关。我们假设，点头综合征患儿脑脊液（CSF）和血浆中改变的免疫激活可能为该癫痫障碍的发病机制和进展提供一些见解。
我们在乌干达北部受点头综合征影响的 3 个地区进行了一项病例对照研究，纳入了 154 名患有长期点头综合征的 8 岁及以上儿童（病例组）和 154 名年龄匹配的健康社区对照儿童（对照组）。对照组 CSF 样本取自乌干达在常规随访中患有血液系统恶性肿瘤但已缓解的儿童。使用 ELISA 或多重 Luminex 检测试剂盒检测血浆和 CSF 中的免疫激活和炎症标志物（细胞因子和趋化因子）以及补体激活（C5a）。通过检测抗 O 旋盘尾丝虫 IgG 水平来评估 O 旋盘尾丝虫感染。
研究人群的平均年龄（标准差）为 15.1（1.9）岁，从诊断到入组的点头综合征平均病程为 8.3（2.7）年。与社区儿童（86/154（55.8%））相比，多数点头综合征患儿（147/154（95.4%））曾接触过 O 旋盘尾丝虫，比值比为 17.04（95%置信区间：7.33，45.58），P<.001。与对照组相比，点头综合征患儿的 CSF 中 C5a 升高（P<.0001）。在进行多重比较校正后，病例组和对照组 CSF 标志物的水平相当。与社区对照组相比，点头综合征患儿的血浆中 IL-10、APRIL、CCL5（RANTES）、CCL2、CXCL13 和 MMP-9 水平较低（所有比较均 P<.05；多重比较）。与社区儿童相比，点头综合征患儿的血浆 CRP 升高，且与疾病严重程度相关。
点头综合征与接触 O 旋盘尾丝虫有关。与对照组相比，患有长期点头综合征症状的患儿 CSF 中存在补体激活，血浆中存在免疫激活改变的证据。
