早期血浆生物标志物动态谱与急性缺血性卒中预后相关。

Early plasma biomarker dynamic profiles are associated with acute ischemic stroke outcomes.

作者信息

Correia Manuel, Silva Isabel, Gabriel Denis, Simrén Joel, Carneiro Angelo, Ribeiro Sara, Dória Hugo Mota, Varela Ricardo, Aires Ana, Minta Karolina, Antunes Rui, Felgueiras Rui, Castro Pedro, Blenow Kaj, Magalhães Rui, Zetterberg Henrik, Maia Luis F

机构信息

Department of Neurology, Centro Hospitalar Universitário do Porto, Porto, Portugal.

Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.

出版信息

Eur J Neurol. 2022 Jun;29(6):1630-1642. doi: 10.1111/ene.15273. Epub 2022 Feb 20.

DOI:10.1111/ene.15273

PMID:35124870

Abstract

BACKGROUND

Early outcome prediction after acute ischemic stroke (AIS) might be improved with blood-based biomarkers. We investigated whether the longitudinal profile of a multi-marker panel could predict the outcome of successfully recanalized AIS patients.

METHODS

We used ultrasensitive single-molecule array (Simoa) to measure glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total-tau (t-tau) and ELISA for brevican in a prospective study of AIS patients with anterior circulation large vessel occlusion successfully submitted to thrombectomy. Plasma was obtained at admission, upon treatment, 24 h and 72 h after treatment. Clinical and neuroimaging outcomes were assessed independently.

RESULTS

Thirty-five patients (64.8%) had good early clinical or neuroimaging outcome. Baseline biomarker levels did not distinguish between outcomes. However, longitudinal intra-individual biomarker changes followed different dynamic profiles with time and according to outcome. GFAP levels exhibited an early and prominent increase between admission and just after treatment. NfL increase was less pronounced between admission and up to 24 h. T-tau increased between treatment and 24 h. Interestingly, GFAP rate-of-change (pg/ml/h) between admission and immediately after recanalization had a good discriminative capacity between clinical outcomes (AUC = 0.88, p < 0.001), which was higher than admission CT-ASPECTS (AUC = 0.75, p < 0.01). T-tau rate-of-change provided moderate discriminative capacity (AUC = 0.71, p < 0.05). Moreover, in AIS patients with admission CT-ASPECTS <9 both GFAP and NfL rate-of-change were good outcome predictors (AUC = 0.82 and 0.77, p < 0.05).

CONCLUSION

Early GFAP, t-tau and NfL rate-of-change in plasma can predict AIS clinical and neuroimaging outcome after successful recanalization. Such dynamic measures match and anticipate neuroimaging predictive capacity, potentially improving AIS patient stratification for treatment, and targeting individualized stroke care.

摘要

背景

基于血液的生物标志物可能会改善急性缺血性卒中（AIS）后的早期预后预测。我们研究了多标志物组合的纵向变化情况是否能够预测成功再通的AIS患者的预后。

方法

在一项对成功接受血栓切除术的前循环大血管闭塞性AIS患者的前瞻性研究中，我们使用超灵敏单分子阵列（Simoa）测量胶质纤维酸性蛋白（GFAP）、神经丝轻链（NfL）、总tau蛋白（t-tau），并采用酶联免疫吸附测定法（ELISA）检测 brevican。在入院时、治疗时、治疗后24小时和72小时采集血浆。独立评估临床和神经影像学预后。

结果

35例患者（64.8%）早期临床或神经影像学预后良好。基线生物标志物水平无法区分预后情况。然而，个体内生物标志物的纵向变化随时间以及预后情况呈现出不同的动态变化模式。GFAP水平在入院至治疗刚结束后呈现出早期且显著的升高。NfL在入院至24小时之间的升高不太明显。t-tau在治疗至24小时之间升高。有趣的是，入院至再通后即刻的GFAP变化率（pg/ml/h）在临床预后之间具有良好的鉴别能力（曲线下面积[AUC]=0.88，p<0.001），高于入院时的CT-ASPECTS评分（AUC=0.75，p<0.01）。t-tau变化率具有中等鉴别能力（AUC=0.71，p<0.05）。此外，在入院时CT-ASPECTS评分<9的AIS患者中，GFAP和NfL变化率均为良好的预后预测指标（AUC分别为0.82和0.77，p<0.05）。