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脑源性 Tau 蛋白用于监测急性缺血性卒中的脑损伤

Brain-derived Tau for Monitoring Brain Injury in Acute Ischemic Stroke.

作者信息

Vlegels Naomi, Gonzalez-Ortiz Fernando, Knuth Nicoló Luca, Khalifeh Nada, Gesierich Benno, Müller Franziska, Müller Philipp, Klein Matthias, Dimitriadis Konstantinos, Franzmeier Nicolai, Liebig Thomas, Duering Marco, Reidler Paul, Dichgans Martin, Karikari Thomas K, Blennow Kaj, Tiedt Steffen

机构信息

Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Germany.

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

出版信息

medRxiv. 2023 Nov 19:2023.11.18.23298728. doi: 10.1101/2023.11.18.23298728.

Abstract

The evolution of infarcts varies widely among patients with acute ischemic stroke (IS) and influences treatment decisions. Neuroimaging is not applicable for frequent monitoring and there is no blood-based biomarker to track ongoing brain injury in acute IS. Here, we examined the utility of plasma brain-derived tau (BD-tau) as a biomarker for brain injury in acute IS. We conducted the prospective, observational Precision Medicine in Stroke [PROMISE] study with serial blood sampling upon hospital admission and at days 2, 3, and 7 in patients with acute ischemic stroke (IS) and for comparison, in patients with stroke mimics (SM). We determined the temporal course of plasma BD-tau, its relation to infarct size and admission imaging-based metrics of brain injury, and its value to predict functional outcome. Upon admission (median time-from-onset, 4.4h), BD-tau levels in IS patients correlated with ASPECTS (=-0.21, <.0001) and were predictive of final infarct volume (=0.26, <.0001). In contrast to SM patients, BD-tau levels in IS patients increased from admission (median, 2.9 pg/ml [IQR, 1.8-4.8]) to day 2 (median time-from-onset, 22.7h; median BD-tau, 5.0 pg/ml [IQR, 2.6-10.3]; <.0001). The rate of change of BD-tau from admission to day 2 was significantly associated with collateral supply (=0.10, <.0001) and infarct progression (=0.58, <.0001). At day 2, BD-tau was predictive of final infarct volume (=0.59, <.0001) and showed superior value for predicting the 90-day mRS score compared with final infarct volume. In conclusion, in 502 patients with acute IS, plasma BD-tau was associated with imaging-based metrics of brain injury upon admission, increased within the first 24 hours in correlation with infarct progression, and at 24 hours was superior to final infarct volume in predicting 90-day functional outcome. Further research is needed to determine whether BD-tau assessments can inform decision-making in stroke care.

摘要

急性缺血性卒中(IS)患者梗死灶的演变差异很大,且会影响治疗决策。神经影像学不适用于频繁监测,目前尚无基于血液的生物标志物可用于追踪急性IS患者持续的脑损伤情况。在此,我们研究了血浆脑源性tau蛋白(BD-tau)作为急性IS脑损伤生物标志物的效用。我们开展了前瞻性观察性卒中精准医学[PROMISE]研究,对急性缺血性卒中(IS)患者在入院时以及第2、3和7天进行系列血样采集,并对疑似卒中(SM)患者进行对比研究。我们确定了血浆BD-tau的时间进程、其与梗死灶大小及基于入院时影像学的脑损伤指标的关系,以及其预测功能转归的价值。入院时(发病至入院的中位时间为4.4小时),IS患者的BD-tau水平与ASPECTS评分相关(=-0.21,<.0001),并可预测最终梗死体积(=0.26,<.0001)。与SM患者不同,IS患者的BD-tau水平从入院时(中位值,2.9 pg/ml[四分位间距,1.8 - 4.8])升高至第2天(发病至入院的中位时间为22.7小时;BD-tau中位值,5.0 pg/ml[四分位间距,2.6 - 10.3];<.0001)。从入院到第2天BD-tau的变化率与侧支循环供血(=0.10,<.0001)和梗死进展(=0.58,<.0001)显著相关。在第2天,BD-tau可预测最终梗死体积(=0.59,<.0001),且与最终梗死体积相比,在预测90天改良Rankin量表(mRS)评分方面显示出更高的价值。总之,在502例急性IS患者中,血浆BD-tau与入院时基于影像学的脑损伤指标相关,在最初24小时内随梗死进展而升高,且在24小时时预测90天功能转归优于最终梗死体积。需要进一步研究以确定BD-tau评估是否能为卒中治疗决策提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f45/10680879/e943a871d996/nihpp-2023.11.18.23298728v1-f0001.jpg

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