Luger Sebastian, Witsch Jens, Dietz Andreas, Hamann Gerhard F, Minnerup Jens, Schneider Hauke, Sitzer Matthias, Wartenberg Katja E, Niessner Marion, Foerch Christian
Department of Neurology, Goethe-University, Frankfurt am Main, Germany.
Charité Center for Stroke Research Berlin (CSB), Berlin, Germany.
Clin Chem. 2017 Jan;63(1):377-385. doi: 10.1373/clinchem.2016.263335. Epub 2016 Nov 23.
Recent studies have suggested that glial fibrillary acidic protein (GFAP) serum concentrations distinguish between intracerebral hemorrhage (ICH) and ischemic stroke (IS) shortly after symptom onset. In this prospective multicenter trial we validated GFAP in an independent patient cohort and assessed the quantitative relationship between GFAP release, bleeding size, and localization.
We included patients with a persistent neurological deficit (NIH Stroke Scale ≥4) suggestive of stroke within 6 h of symptom onset. Blood samples were drawn at hospital admission. GFAP serum concentrations were measured using an electrochemiluminometric immunoassay. Primary endpoint was the final diagnosis established at hospital discharge (ICH, IS, or stroke mimic).
202 patients were included (45 with ICH, 146 with IS, 11 stroke mimics). GFAP concentrations were significantly higher in ICH than in IS patients [median (interquartile range) 0.16 μg/L (0.04-3.27) vs 0.01 μg/L (0.01-0.01), P <0.001]. A GFAP cutoff of 0.03 μg/L provided a sensitivity of 77.8% and a specificity of 94.2% in distinguishing ICH from IS and stroke mimics [ROC analysis area under the curve 0.872 (95% CI, 0.802-0.942), P <0.001]. GFAP serum concentrations were positively correlated with ICH volume. Lobar ICH volumes were larger and thus associated with higher GFAP concentrations as compared to deep ICH.
Serum GFAP was confirmed to be a biomarker indicating ICH in patients presenting with acute stroke symptoms. Very small ICH may be missed owing to less tissue destruction.
最近的研究表明,胶质纤维酸性蛋白(GFAP)血清浓度可在症状出现后不久区分脑出血(ICH)和缺血性中风(IS)。在这项前瞻性多中心试验中,我们在一个独立的患者队列中验证了GFAP,并评估了GFAP释放、出血量和出血部位之间的定量关系。
我们纳入了症状出现后6小时内出现持续性神经功能缺损(美国国立卫生研究院卒中量表≥4)提示中风的患者。入院时采集血样。使用电化学发光免疫分析法测量GFAP血清浓度。主要终点是出院时确定的最终诊断(ICH、IS或疑似中风)。
纳入202例患者(45例ICH,146例IS,11例疑似中风)。ICH患者的GFAP浓度显著高于IS患者[中位数(四分位间距)0.16μg/L(0.04 - 3.27)对0.01μg/L(0.01 - 0.01),P <0.001]。GFAP临界值为0.03μg/L时,区分ICH与IS和疑似中风的敏感性为77.8%,特异性为94.2%[ROC分析曲线下面积0.872(95%CI,0.802 - 0.942),P <0.001]。GFAP血清浓度与ICH体积呈正相关。与深部ICH相比,脑叶ICH体积更大,因此GFAP浓度更高。
血清GFAP被证实是急性中风症状患者中指示ICH的生物标志物。由于组织破坏较少,可能会漏诊非常小的ICH。