Andrew Reisner, Ali M Alawieh, Jacob R Lepard, Anna V Baer, Youssef M Zohdy, Joshua J Chern, Stefania Mondello, Laura M Johnson, Adrianna L Westbrook, Kevin K Wang, Firas Kobeissy, Rebekah Mannix, Geoffrey T Manley, Laura S Blackwell
{"title":"Biomarker-informed prediction of neurosurgical intervention in pediatric traumatic brain injury: a proof-of-concept study.","authors":"Andrew Reisner, Ali M Alawieh, Jacob R Lepard, Anna V Baer, Youssef M Zohdy, Joshua J Chern, Stefania Mondello, Laura M Johnson, Adrianna L Westbrook, Kevin K Wang, Firas Kobeissy, Rebekah Mannix, Geoffrey T Manley, Laura S Blackwell","doi":"10.3171/2026.4.PEDS25694","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Emerging traumatic brain injury (TBI) guidelines increasingly recognize the role of blood-based biomarkers in improving diagnostic and triage accuracy, yet their integration into pediatric care remains limited and underexplored. This study examined the performance of a blood-based biomarker panel in predicting which pediatric patients with TBI received neurosurgical intervention (NSI).</p><p><strong>Methods: </strong>This was a prospective cohort study of 425 children (aged 0-17 years) treated at a pediatric tertiary hospital between March 2017 and June 2021 with nonpenetrating TBI (Glasgow Coma Scale [GCS] score 3-15). Standard of care was rendered. NSI included craniotomy, craniectomy, external ventricular drain (EVD) placement, and intracranial pressure (ICP) monitor placement. Blood samples collected within 24 hours of injury were measured for plasma glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and total tau (t-tau) with the Quanterix Simoa platform, as well as osteopontin (OPN) quantification via ELISA. Logistic regression and area under the curve (AUC) analysis with 95% confidence intervals (CI) were used to measure predictive discrimination.</p><p><strong>Results: </strong>NSI occurred in 14.35% of patients. These children were younger (mean age 6.0 vs 10.1 years) with more severe injury (median GCS score 9.0 vs 15.0) than those who did not require NSI. All median biomarker concentrations were higher in NSI compared with non-NSI patients (p < 0.001). After age and GCS score were controlled for, GFAP significantly predicted NSI (AUC 0.83, 95% CI 0.75-0.90), defining the best predictive model for NSI.</p><p><strong>Conclusions: </strong>Blood-based biomarkers predicted NSI following pediatric TBI, independent of age and admission GCS score. These findings support further prospective trials to determine whether integrating blood-based biomarkers into clinical triage algorithms and TBI guidelines can improve neurosurgical decision-making and patient outcomes.</p>","PeriodicalId":16549,"journal":{"name":"Journal of neurosurgery. Pediatrics","volume":" ","pages":"1-11"},"PeriodicalIF":2.2000,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neurosurgery. Pediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3171/2026.4.PEDS25694","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Emerging traumatic brain injury (TBI) guidelines increasingly recognize the role of blood-based biomarkers in improving diagnostic and triage accuracy, yet their integration into pediatric care remains limited and underexplored. This study examined the performance of a blood-based biomarker panel in predicting which pediatric patients with TBI received neurosurgical intervention (NSI).
Methods: This was a prospective cohort study of 425 children (aged 0-17 years) treated at a pediatric tertiary hospital between March 2017 and June 2021 with nonpenetrating TBI (Glasgow Coma Scale [GCS] score 3-15). Standard of care was rendered. NSI included craniotomy, craniectomy, external ventricular drain (EVD) placement, and intracranial pressure (ICP) monitor placement. Blood samples collected within 24 hours of injury were measured for plasma glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and total tau (t-tau) with the Quanterix Simoa platform, as well as osteopontin (OPN) quantification via ELISA. Logistic regression and area under the curve (AUC) analysis with 95% confidence intervals (CI) were used to measure predictive discrimination.
Results: NSI occurred in 14.35% of patients. These children were younger (mean age 6.0 vs 10.1 years) with more severe injury (median GCS score 9.0 vs 15.0) than those who did not require NSI. All median biomarker concentrations were higher in NSI compared with non-NSI patients (p < 0.001). After age and GCS score were controlled for, GFAP significantly predicted NSI (AUC 0.83, 95% CI 0.75-0.90), defining the best predictive model for NSI.
Conclusions: Blood-based biomarkers predicted NSI following pediatric TBI, independent of age and admission GCS score. These findings support further prospective trials to determine whether integrating blood-based biomarkers into clinical triage algorithms and TBI guidelines can improve neurosurgical decision-making and patient outcomes.
目的:新出现的创伤性脑损伤(TBI)指南越来越多地认识到基于血液的生物标志物在提高诊断和分诊准确性方面的作用,但它们在儿科护理中的整合仍然有限且未得到充分探索。本研究检验了基于血液的生物标志物面板在预测哪些儿科TBI患者接受神经外科干预(NSI)方面的表现。方法:这是一项前瞻性队列研究,纳入了2017年3月至2021年6月在某儿科三级医院接受非穿透性TBI治疗的425名儿童(0-17岁)(格拉斯哥昏迷量表[GCS]评分为3-15)。已经表现出了谨慎的标准。NSI包括开颅、颅骨切除术、外脑室引流(EVD)放置和颅内压(ICP)监测仪放置。采用Quanterix Simoa平台检测损伤24小时内采集的血液中血浆胶质纤维酸性蛋白(GFAP)、泛素c端水解酶- l1 (UCH-L1)、神经丝光(NfL)和总tau蛋白(t-tau),并通过ELISA检测骨桥蛋白(OPN)。采用Logistic回归和曲线下面积(AUC)分析,95%置信区间(CI)来测量预测判别。结果:NSI发生率为14.35%。这些儿童年龄更小(平均年龄6.0 vs 10.1岁),损伤更严重(中位GCS评分9.0 vs 15.0)。与非NSI患者相比,NSI患者的所有中位生物标志物浓度均较高(p < 0.001)。在控制年龄和GCS评分后,GFAP显著预测NSI (AUC 0.83, 95% CI 0.75-0.90),定义了NSI的最佳预测模型。结论:基于血液的生物标志物预测儿童TBI后的NSI,独立于年龄和入院GCS评分。这些发现支持进一步的前瞻性试验,以确定将基于血液的生物标志物纳入临床分诊算法和TBI指南是否可以改善神经外科决策和患者预后。