Department of Neurology, Goethe-University Hospital Frankfurt, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany.
The Norwegian Air Ambulance Foundation, Oslo, Norway.
Neurocrit Care. 2020 Aug;33(1):39-48. doi: 10.1007/s12028-020-00931-5.
Biomarkers indicative of intracerebral hemorrhage (ICH) may help triage acute stroke patients in the pre-hospital phase. We hypothesized that serum concentration of glial fibrillary acidic protein (GFAP) in combination with ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), measured by a rapid bio-assay, could be used to distinguish ICH from ischemic stroke.
This prospective two-center study recruited patients with a clinical diagnosis of acute stroke both in the pre-hospital phase and at hospital admission (within 4 and 6 h after symptom onset, respectively). Blood samples were analyzed for concentrations of GFAP and UCH-L1 using ELISA techniques. The reference standard was the diagnosis of ICH, ischemic stroke, or stroke mimicking condition achieved after clinical workup including brain imaging.
A total of 251 patients were included (mean age [± SD] 72 ± 15 years; 5 ICH, 23 ischemic strokes and 14 stroke mimics in the pre-hospital part; and 59 ICH, 148 ischemic strokes and 2 stroke mimics in the in-hospital part). Mean delay (± SD) from symptom onset to blood withdrawal was 130 ± 79 min for the pre-hospital patients and 136 ± 86 min for the in-hospital patients. Both GFAP and UCH-L1 serum concentrations were higher in patients having ICH as compared to other diagnoses (GFAP: median 330 ng/L [interquartile range 64-7060, range 8-56,100] vs. 27.5 ng/L [14-57.25, 0-781], p < 0.001; UCH-L1: 401 ng/L [265-764, 133-1812] vs. 338 ng/L [213-549.5, 0-2950], p = 0.025). Area-under-the-curve values were 0.866 (95% CI 0.809-0.924, p < 0.001) for GFAP, and 0.590 (0.511-0.670, p = 0.033) for UCH-L1. Regarding overall diagnostic accuracy, UCH-L1 did not add significantly to the performance of GFAP.
GFAP may differentiate ICH from ischemic stroke and stroke mimics. A point-of-care test to distinguish between ischemic and hemorrhagic strokes might facilitate triage to different treatment pathways or locations, or be used to select patients for trials of ultra-early interventions.
能指示脑出血（ICH）的生物标志物可能有助于在院前阶段对急性脑卒中患者进行分诊。我们假设通过快速生物测定测量的血清胶质纤维酸性蛋白（GFAP）和泛素羧基末端水解酶-L1（UCH-L1）浓度可用于区分 ICH 和缺血性脑卒中。
这项前瞻性的双中心研究招募了在院前阶段和入院时（分别为症状发作后 4 小时和 6 小时内）均具有急性脑卒中临床诊断的患者。使用 ELISA 技术分析 GFAP 和 UCH-L1 的浓度。参考标准是通过包括脑成像在内的临床评估后获得的 ICH、缺血性脑卒中或脑卒中模拟疾病的诊断。
共纳入 251 例患者（平均年龄[±标准差]72±15 岁；院前部分有 5 例 ICH、23 例缺血性脑卒中及 14 例脑卒中模拟病例；入院部分有 59 例 ICH、148 例缺血性脑卒中及 2 例脑卒中模拟病例）。从发病到采血的平均延迟（±标准差）分别为 130±79 分钟和 136±86 分钟。与其他诊断相比，ICH 患者的 GFAP 和 UCH-L1 血清浓度均更高（GFAP：中位数 330ng/L[四分位距 64-7060，范围 8-56100]vs.27.5ng/L[14-57.25，0-781]，p<0.001；UCH-L1：401ng/L[265-764，133-1812]vs.338ng/L[213-549.5，0-2950]，p=0.025）。GFAP 的曲线下面积值为 0.866（95%CI 0.809-0.924，p<0.001），UCH-L1 为 0.590（0.511-0.670，p=0.033）。关于总体诊断准确性，UCH-L1 并未显著提高 GFAP 的性能。
GFAP 可区分 ICH 和缺血性脑卒中及脑卒中模拟病例。一种即时检测方法来区分缺血性卒中和出血性卒中可能有助于分诊到不同的治疗途径或地点，或用于选择接受超早期干预试验的患者。
