血清神经丝轻链和胶质纤维酸性蛋白作为血液生物标记物在预测严重急性缺血性脑卒中功能预后方面的增量价值。

IF 5.8 3区 医学 Q1 CLINICAL NEUROLOGY European Stroke Journal Pub Date : 2024-09-01 Epub Date: 2024-02-24 DOI:10.1177/23969873241234436
Christoph Vollmuth, Cornelia Fiessler, Felipe A Montellano, Alexander M Kollikowski, Fabian Essig, Patrick Oeckl, Lorenzo Barba, Petra Steinacker, Cara Schulz, Kathrin Ungethüm, Judith Wolf, Mirko Pham, Michael K Schuhmann, Peter U Heuschmann, Karl Georg Haeusler, Guido Stoll, Markus Otto, Hermann Neugebauer
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引用次数: 0

摘要

导言:基于血液的生物标志物可改善急性缺血性卒中患者功能预后的预测。神经丝蛋白轻链(NfL)和胶质纤维酸性蛋白(GFAP)作为潜在的生物标志物,尤其是在重症中风患者中的作用尚不清楚:前瞻性、单中心、队列研究,包括入院时患有前循环严重缺血性卒中的连续患者(NIHSS评分⩾ 6分或有机械血栓切除指征)。卒中发生 3 个月后,采用改良兰金量表(mRS)对患者的预后进行评估。血清生物标志物 NfL 和 GFAP 水平采用超灵敏 ELISA 法测定。采用单变量和多变量逻辑回归模型来确定生物标志物水平与功能障碍之间的关系。通过AUROC、校准图(含Emax和Eavg)、Brier-score和R2分析了不同模型的辨别、校准和总体性能,这些变量在之前的研究中被确定为功能结果的重要协变量:2020 年 6 月至 2021 年 8 月间,共纳入 213 名患者[47% 为女性,平均年龄 76(SD ± 12)岁,NIHSS 评分中位数为 13(四分位数间距,IQR 9; 17)]。生物标志物血清水平在入院后 1 [IQR, 1; 2] 天进行中位测量。与 3 个月时 mRS 为 0-2 的患者相比,mRS 为 3-6 的患者血清中的 NfL 水平更高(中位数为 136 pg/ml vs 41 pg/ml):136 pg/ml vs 41 pg/ml; p p 结论:在中风急性期测量的血液生物标志物血清 NfL 和 GFAP 能更好地预测严重急性缺血性中风后的功能预后。这些研究结果需要在独立的外部队列中进行验证:研究注册号:DRKS00022064。
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Incremental value of serum neurofilament light chain and glial fibrillary acidic protein as blood-based biomarkers for predicting functional outcome in severe acute ischemic stroke.

Introduction: Blood-based biomarkers may improve prediction of functional outcome in patients with acute ischemic stroke. The role of neurofilament light chain (NfL) and glial fibrillary acidic (GFAP) as potential biomarkers especially in severe stroke patients is unknown.

Patients and methods: Prospective, monocenter, cohort study including consecutive patients with severe ischemic stroke in the anterior circulation on admission (NIHSS score ⩾ 6 points or indication for mechanical thrombectomy). Outcome was assessed 3 months after the index stroke by the modified Rankin Scale (mRS). Serum biomarkers levels of NfL and GFAP were determined by ultrasensitive ELISA. Univariate and multivariate logistic regression models were performed to determine the association of biomarker levels and functional disability. Discrimination, calibration, and overall performance were analyzed in different models via AUROC, calibration plots (with Emax and Eavg), Brier-score and R2 using variables, identified as important covariates for functional outcome in previous studies.

Results: Between 06/2020 and 08/2021, 213 patients were included [47% female, mean age 76 (SD ± 12) years, median NIHSS score 13 (interquartile range, IQR 9; 17)]. Biomarker serum levels were measured at a median of 1 [IQR, 1; 2] day after admission. Compared to patients with mRS 0-2 at 3 months, patients with mRS 3-6 had higher serum levels of NfL (median: 136 pg/ml vs 41 pg/ml; p < 0.0001) and GFAP (700 ng/ml vs 9.6 ng/ml; p < 0.0001). Both biomarkers were significantly associated with functional outcome [adjusted logistic regression, odds ratio (95% CI) for NfL: 2.63 (1.62; 4.56), GFAP: 2.16 (1.58; 3.09)]. In all models the addition of serum NfL led to a significant improvement in the AUROC, as did the addition of serum GFAP. Calibration plots showed high agreement between the predicted and observed outcomes and after addition of the two blood-based biomarkers there was an improvement of the overall performance.

Conclusion: Prediction of functional outcome after severe acute ischemic stroke was improved by the blood-based biomarkers serum NfL and GFAP, measured in the acute phase of stroke. These findings have to be replicated in independent external cohorts.Study registration: DRKS00022064.

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来源期刊
CiteScore
7.50
自引率
6.60%
发文量
102
期刊介绍: Launched in 2016 the European Stroke Journal (ESJ) is the official journal of the European Stroke Organisation (ESO), a professional non-profit organization with over 1,400 individual members, and affiliations to numerous related national and international societies. ESJ covers clinical stroke research from all fields, including clinical trials, epidemiology, primary and secondary prevention, diagnosis, acute and post-acute management, guidelines, translation of experimental findings into clinical practice, rehabilitation, organisation of stroke care, and societal impact. It is open to authors from all relevant medical and health professions. Article types include review articles, original research, protocols, guidelines, editorials and letters to the Editor. Through ESJ, authors and researchers have gained a new platform for the rapid and professional publication of peer reviewed scientific material of the highest standards; publication in ESJ is highly competitive. The journal and its editorial team has developed excellent cooperation with sister organisations such as the World Stroke Organisation and the International Journal of Stroke, and the American Heart Organization/American Stroke Association and the journal Stroke. ESJ is fully peer-reviewed and is a member of the Committee on Publication Ethics (COPE). Issues are published 4 times a year (March, June, September and December) and articles are published OnlineFirst prior to issue publication.
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