Castaño-Leon Ana M, Sánchez Carabias Cristina, Hilario Amaya, Ramos Ana, Navarro-Main Blanca, Paredes Igor, Munarriz Pablo M, Panero Irene, Eiriz Fernández Carla, García-Pérez Daniel, Moreno-Gomez Luis Miguel, Esteban-Sinovas Olga, Garcia Posadas Guillermo, Gomez Pedro A, Lagares Alfonso
1Department of Neurosurgery, Research Institute i+12-CIBERESP, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid.
2Research Institute i+12-CIBERESP, Hospital Universitario 12 de Octubre, Madrid.
J Neurosurg. 2022 Jul 15;138(2):454-464. doi: 10.3171/2022.5.JNS22638. Print 2023 Feb 1.
Diagnosis of traumatic axonal injury (TAI) is challenging because of its underestimation by conventional MRI and the technical requirements associated with the processing of diffusion tensor imaging (DTI). Serum biomarkers seem to be able to identify patients with abnormal CT scanning findings, but their potential role to assess TAI has seldomly been explored.
Patients with all severities of traumatic brain injury (TBI) were prospectively included in this study between 2016 and 2021. They underwent blood extraction within 24 hours after injury and imaging assessment, including DTI. Serum concentrations of glial fibrillary acidic protein, total microtubule-associated protein (t-Tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NfL) were measured using an ultrasensitive Simoa multiplex assay panel, a digital form of enzyme-linked immunosorbent assay. The Glasgow Outcome Scale-Extended score was determined at 6 months after TBI. The relationships between biomarker concentrations, volumetric analysis of corpus callosum (CC) lesions, and fractional anisotropy (FA) were analyzed by nonparametric tests. The prognostic utility of the biomarker was determined by calculating the C-statistic and an ordinal regression analysis.
A total of 87 patients were included. Concentrations of all biomarkers were significantly higher for patients compared with controls. Although the concentration of the biomarkers was affected by the presence of mass lesions, FA of the CC was an independent factor influencing levels of UCH-L1 and NfL, which positioned these two biomarkers as better surrogates of TAI. Biomarkers also performed well in determining patients who would have had unfavorable outcome. NfL and the FA of the CC are independent complementary factors related to outcome.
UCH-L1 and NfL seem to be the biomarkers more specific to detect TAI. The concentration of NfL combined with the FA of the CC might help predict long-term outcome.
创伤性轴索损伤(TAI)的诊断具有挑战性,因为传统磁共振成像(MRI)对其评估不足,且扩散张量成像(DTI)处理存在技术要求。血清生物标志物似乎能够识别出CT扫描结果异常的患者,但其在评估TAI方面的潜在作用鲜有研究。
2016年至2021年间,前瞻性纳入了所有严重程度的创伤性脑损伤(TBI)患者。他们在受伤后24小时内接受采血及成像评估,包括DTI。使用超灵敏单分子阵列免疫分析检测板(一种数字形式的酶联免疫吸附测定)测量血清中胶质纤维酸性蛋白、总微管相关蛋白(t-Tau)、泛素C末端水解酶L1(UCH-L1)和神经丝轻链(NfL)的浓度。在TBI后6个月确定格拉斯哥预后量表扩展评分。通过非参数检验分析生物标志物浓度、胼胝体(CC)病变的体积分析和各向异性分数(FA)之间的关系。通过计算C统计量和有序回归分析确定生物标志物的预后效用。
共纳入87例患者。与对照组相比,所有生物标志物的浓度在患者中均显著更高。尽管生物标志物的浓度受占位性病变的影响,但CC的FA是影响UCH-L1和NfL水平的独立因素,这使得这两种生物标志物成为TAI更好的替代指标。生物标志物在确定预后不良的患者方面也表现良好。NfL和CC的FA是与预后相关的独立互补因素。
UCH-L1和NfL似乎是检测TAI更具特异性的生物标志物。NfL浓度与CC的FA相结合可能有助于预测长期预后。