利用血清生物标志物和弥散张量成像预测轻度创伤性脑损伤且CT正常患者的恢复情况（CENTER-TBI）：一项观察性队列研究
Predicting recovery in patients with mild traumatic brain injury and a normal CT using serum biomarkers and diffusion tensor imaging (CENTER-TBI): an observational cohort study.
作者信息
Richter Sophie, Winzeck Stefan, Correia Marta M, Czeiter Endre, Whitehouse Daniel, Kornaropoulos Evgenios N, Williams Guy B, Verheyden Jan, Das Tilak, Tenovuo Olli, Posti Jussi P, Vik Anne, Moen Kent Gøran, Håberg Asta K, Wang Kevin, Buki Andras, Maas Andrew, Steyerberg Ewout, Menon David K, Newcombe Virginia F J
机构信息
Department of Medicine, University of Cambridge, Cambridge, UK.
MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
出版信息
EClinicalMedicine. 2024 Aug 8;75:102751. doi: 10.1016/j.eclinm.2024.102751. eCollection 2024 Sep.
BACKGROUND
Even patients with normal computed tomography (CT) head imaging may experience persistent symptoms for months to years after mild traumatic brain injury (mTBI). There is currently no good way to predict recovery and triage patients who may benefit from early follow-up and targeted intervention. We aimed to assess if existing prognostic models can be improved by serum biomarkers or diffusion tensor imaging metrics (DTI) from MRI, and if serum biomarkers can identify patients for DTI.
METHODS
We included 1025 patients aged >18 years with a Glasgow Coma Score >12 and normal CT from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study which recruited between December 19,2014 and December 17, 2017 (NCT02210221). Biomarkers (GFAP, NFL, S100B) were obtained at a median of 8.8 h (Q1-Q3 4.2-16.7) and DTI at 13 days (3-19) after injury. DTI metrics were available in 153 patients for 48 white matter tracts (ICBM-DTI-81 atlas). Incomplete recovery at three months was defined as an extended Glasgow Outcome Scale score <8. Existing prognostic models were fitted with and without biomarkers, or with and without DTI, and internally validated using bootstrapping.
FINDINGS
385 (38%) patients had incomplete recovery. Adding biomarkers did not improve performance beyond the best existing clinical prognostic model [optimism-corrected AUC 0.69 (95% CI 0.65-0.72) and R 17% (11-22)]. Adding DTI metrics significantly enhanced all models [best optimism-corrected AUC 0.82 (0.79-0.85) and R 75% (39-100)]. The top three prognostic tracts were the left posterior thalamic radiation, left superior cerebellar peduncle and right uncinate fasciculus. Serum biomarkers could have avoided 1 in 5 DTI scans, with GFAP <12 h and NFL 12-24 h from injury performing best.
INTERPRETATION
DTI substantially improved existing prognostic models for functional outcome in patients with mTBI and a normal CT, and biomarkers could help select patients for MRI. If validated, DTI could allow for targeted follow-up and enrichment of clinical trials of early interventions to improve outcome.
FUNDING
EU Seventh Framework Programme, Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, NeuroTrauma Sciences.
背景
即使头部计算机断层扫描（CT）成像正常的患者，在轻度创伤性脑损伤（mTBI）后也可能持续数月至数年出现症状。目前尚无很好的方法来预测恢复情况并对可能从早期随访和针对性干预中获益的患者进行分类。我们旨在评估现有的预后模型是否可以通过血清生物标志物或磁共振成像（MRI）的扩散张量成像指标（DTI）得到改进，以及血清生物标志物是否可以识别适合进行DTI检查的患者。
方法
我们纳入了1025名年龄大于18岁、格拉斯哥昏迷评分大于12且CT正常的患者，这些患者来自于欧洲创伤性脑损伤协作有效性研究（CENTER-TBI），该研究于2014年12月19日至2017年12月17日期间招募（NCT02210221）。在受伤后中位数8.8小时（四分位间距Q1-Q3为4.2-16.7）获取生物标志物（胶质纤维酸性蛋白GFAP、神经丝轻链NFL、S100B），并在受伤后13天（3-19天）进行DTI检查。153名患者的48条白质束（ICBM-DTI-81图谱）有DTI指标。三个月时恢复不完全定义为扩展格拉斯哥预后量表评分<8分。现有的预后模型分别在纳入和不纳入生物标志物、或纳入和不纳入DTI的情况下进行拟合，并使用自抽样法进行内部验证。
结果
385名（38%）患者恢复不完全。添加生物标志物并没有使性能超过现有的最佳临床预后模型[乐观校正的曲线下面积（AUC）为0.69（95%可信区间0.65-0.72），R为17%（11-22）]。添加DTI指标显著增强了所有模型[最佳乐观校正的AUC为0.82（0.79-0.85），R为75%（39-100）]。预后效果最好的三条白质束是左侧丘脑后辐射、左侧小脑上脚和右侧钩束。血清生物标志物可以避免五分之一的DTI扫描，受伤后GFAP<12小时和NFL在12-24小时时效果最佳。
解读
DTI显著改善了mTBI且CT正常患者功能预后的现有预后模型，生物标志物可以帮助选择适合进行MRI检查的患者。如果得到验证，DTI可以实现有针对性的随访，并丰富早期干预改善预后的临床试验。
资金来源
欧盟第七框架计划、汉诺洛蕾·科尔基金会、一心基金、英特格拉生命科学公司、神经创伤科学公司。
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