唾液生物标志物与儿童脑震荡亚型之间的关联

文献信息

中文摘要

目的： 检验特定唾液生物标志物与儿童脑震荡亚型相关的假设。
研究设计： 开展了一项横断面多中心研究，于2021年8月至2024年1月纳入确诊脑震荡后10天内的11-20岁儿童患者以及未受伤的健康对照。脑震荡亚型，包括焦虑/情绪、认知、头痛/偏头痛、眼部和前庭亚型，采用先前发表的通用数据元素标准进行盲法裁定。参与者在受伤后10天内完成了多域脑震荡评估并提供被动流涎唾液样本。数字免疫组织化学检测测量了代表各亚型的混合唾液样本中82种应激反应生物标志物组合。倍数变化（FC）阈值（≥2倍）和变异系数（CV）用于识别儿童脑震荡亚型中升高的生物标志物。
结果： 共纳入156名脑震荡参与者（平均年龄=15.3±2.1岁；46%为女性）和15名对照。检测分析识别出21种在至少1种脑震荡亚型中较对照升高≥2倍的生物标志物。其中6种生物标志物具有亚型特异性，包括焦虑/情绪的催产素（FC=3.3；CV=13%）；认知的缺氧诱导因子α1、神经丝轻链和c-Fos即刻早期转录因子（FC=7.9、3.0、2.9；CV=18%、22%、18%）；以及头痛/偏头痛的B型利钠肽和Toll样受体2（FC=2.0、2.2；CV=9%、14%）。神经病靶酯酶在各亚型中均升高（FC：4.0-16.7；CV：5%-25%）。
结论： 结果识别出唾液生物标志物与儿童脑震荡亚型之间的关联，特别是焦虑/情绪、认知和头痛/偏头痛亚型。这些发现为使用唾液生物标志物方法补充现有多域临床评估提供了初步支持；然而，在临床实施之前还需要外部验证和更多研究。

英文摘要

OBJECTIVE: To test the hypothesis that specific saliva-based biomarkers are associated with pediatric concussion subtypes.
STUDY DESIGN: A cross-sectional multicenter study was conducted from August 2021 to January 2024 enrolling pediatric patients aged 11-20 years within 10 days of a diagnosed concussion and uninjured healthy controls. Concussion subtypes, including anxiety/mood, cognitive, headache/migraine, ocular, and vestibular, were blindly adjudicated using previously published common data elements criteria. Participants completed a multidomain concussion assessment and provided a passive drool saliva sample within 10 days of injury. Digital immunohistochemistry assays measured a panel of 82 stress response biomarkers in pooled saliva samples representing individual subtypes. Fold-change (FC) thresholds (≥2-fold) and coefficients of variability (CVs) identified elevated biomarkers in pediatric concussion subtypes.
RESULTS: A total of 156 participants (mean age = 15.3 ± 2.1; 46% female) with concussion and 15 controls were enrolled. Analyses of assays identified 21 biomarkers with ≥2-fold elevation compared with controls in at least 1 concussion subtype. Six of these biomarkers were subtype-specific, including oxytocin for anxiety/mood (FC = 3.3; CV = 13%); hypoxia-induced factor alpha 1, neurofilament light, and c-Fos immediate early transcription factor for cognitive (FCs = 7.9, 3.0, 2.9; CVs = 18%, 22%, 18%); and B-type natriuretic peptide and Toll-like receptor 2 for headache/migraine (FCs = 2.0, 2.2; CVs = 9%, 14%). Neuropathy target esterase was elevated across subtypes (FCs: 4.0-16.7; CVs: 5%-25%).
CONCLUSIONS: Results identified an association between saliva-based biomarkers and pediatric concussion subtypes, specifically the anxiety/mood, cognitive, and headache/migraine subtypes. These findings provide preliminary support for using a saliva-based biomarker approach to complement existing multidomain clinical assessments; however, external validation and additional research are needed before clinical implementation.