Stefani Marco A, Modkovski Rafael, Hansel Gisele, Zimmer Eduardo R, Kopczynski Afonso, Muller Alexandre P, Strogulski Nathan R, Rodolphi Marcelo S, Carteri Randhall K, Schmidt André P, Oses Jean P, Smith Douglas H, Portela Luis V
Laboratory of Neuroanatomy Department of Morphological Sciences Federal University of Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil.
Laboratory of Neurotrauma Department of Biochemistry Post-graduation Program in Biochemistry Federal University of Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil.
Ann Clin Transl Neurol. 2017 May 4;4(6):392-402. doi: 10.1002/acn3.416. eCollection 2017 Jun.
Clinical neurological assessment is challenging for severe traumatic brain injury (TBI) patients in the acute setting. Waves of neurochemical abnormalities that follow TBI may serve as fluid biomarkers of neurological status. We assessed the cerebrospinal fluid (CSF) levels of glutamate, lactate, BDNF, and GDNF, to identify potential prognostic biomarkers of neurological outcome.
This cross-sectional study was carried out in a total of 20 consecutive patients (mean [SD] age, 29 [13] years; M/F, 9:1) with severe TBI Glasgow Coma Scale ≤ 8 and abnormal computed tomography scan on admission. Patients were submitted to ventricular drainage and had CSF collected between 2 and 4 h after hospital admission. Patients were then stratified according to two clinical outcomes: deterioration to brain death (nonsurvival, = 6) or survival (survival, = 14), within 3 days after hospital admission. CSF levels of brain-derived substances were compared between nonsurvival and survival groups. Clinical and neurological parameters were also assessed.
Glutamate and lactate are significantly increased in nonsurvival relative to survival patients. We tested the accuracy of both biomarkers to discriminate patient outcome. Setting a cutoff of >57.75, glutamate provides 80.0% of sensitivity and 84.62% of specificity (AUC: 0.8214, 95% CL: 54.55-98.08%; and a cutoff of >4.65, lactate has 100% of sensitivity and 85.71% of specificity (AUC: 0.8810, 95% CL: 54.55-98.08%). BDNF and GDNF did not discriminate poor outcome.
This early study suggests that glutamate and lactate concentrations at hospital admission accurately predict death within 3 days after severe TBI.
在急性情况下，对重度创伤性脑损伤（TBI）患者进行临床神经学评估具有挑战性。TBI后出现的神经化学异常波动可能作为神经状态的液体生物标志物。我们评估了脑脊液（CSF）中谷氨酸、乳酸、脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）的水平，以确定神经功能预后的潜在生物标志物。
本横断面研究共纳入20例连续的重度TBI患者（平均[标准差]年龄，29[13]岁；男/女，9:1），格拉斯哥昏迷量表评分≤8，入院时计算机断层扫描异常。患者接受脑室引流，并在入院后2至4小时收集脑脊液。然后根据两种临床结局对患者进行分层：入院后3天内恶化至脑死亡（未存活，n = 6）或存活（存活，n = 14）。比较未存活组和存活组脑脊液中脑源性物质的水平。还评估了临床和神经学参数。
与存活患者相比，未存活患者的谷氨酸和乳酸水平显著升高。我们测试了这两种生物标志物区分患者结局的准确性。设定谷氨酸>57.75的临界值时，其敏感性为80.0%，特异性为84.62%（曲线下面积：0.8214，95%可信区间：54.55 - 98.08%）；设定乳酸>4.65的临界值时，其敏感性为100%，特异性为85.71%（曲线下面积：0.8810，95%可信区间：54.55 - 98.08%）。BDNF和GDNF不能区分不良结局。
这项早期研究表明，入院时谷氨酸和乳酸浓度可准确预测重度TBI后3天内的死亡情况。
