Background Plasma glial fibrillary acidic protein (GFAP) and tau are promising markers for differentiating acute cerebral ischemia (ACI) and hemorrhagic stroke (HS), but their prehospital dynamics and usefulness are unknown. Methods We performed ultra-sensitivite single-molecule array (Simoa®) measurements of plasma GFAP and total tau in a stroke code patient cohort with cardinal stroke symptoms [National Institutes of Health Stroke Scale (NIHSS) ≥3]. Sequential sampling included 2 ultra-early samples, and a follow-up sample on the next morning. Results We included 272 cases (203 ACI, 60 HS, and 9 stroke mimics). Median (IQR) last-known-well to sampling time was 53 (35–90) minutes for initial prehospital samples, 90 (67–130) minutes for secondary acute samples, and 21 (16–24) hours for next morning samples. Plasma GFAP was significantly higher in patients with HS than ACI (P < 0.001 for <1 hour and <3 hour prehospital samples, and <3 hour secondary samples), while total tau showed no intergroup difference. The prehospital GFAP release rate (pg/mL/minute) occurring between the 2 very early samples was significantly higher in patients with HS than ACI [2.4 (0.6–14.1)] versus 0.3 (−0.3–0.9) pg/mL/minute, P < 0.001. For cases with <3 hour prehospital sampling (ACI n = 178, HS n = 59), a combined rule (prehospital GFAP >410 pg/mL, or prehospital GFAP 90–410 pg/mL together with GFAP release >0.6 pg/mL/minute) enabled ruling out HS with high certainty (NPV 98.4%) in 68% of patients with ACI (sensitivity for HS 96.6%, specificity 68%, PPV 50%). Conclusions In comparison to single-point measurement, monitoring the prehospital GFAP release rate improves ultra-early differentiation of stroke subtypes. With serial measurement GFAP has potential to improve future prehospital stroke diagnostics.

中文翻译：

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通过测量GFAP的院前释放率对急性脑缺血和出血性卒中进行超早期鉴别诊断

背景 血浆胶质纤维酸性蛋白 (GFAP) 和 tau 是区分急性脑缺血 (ACI) 和出血性中风 (HS) 的有希望的标志物，但它们的院前动力学和有用性尚不清楚。方法 我们对具有主要卒中症状 [美国国立卫生研究院卒中量表 (NIHSS) ≥3] 的卒中代码患者队列进行了血浆 GFAP 和总 tau 的超灵敏单分子阵列 (Simoa®) 测量。顺序采样包括2个超早期样本，以及次日早上的后续样本。结果 我们纳入了 272 例（203 例 ACI、60 例 HS 和 9 例中风模拟）。中值 (IQR) 最后已知的采样时间为初始院前样本 53 (35-90) 分钟，二次急性样本为 90 (67-130) 分钟，次日早晨样本为 21 (16-24) 小时。HS 患者的血浆 GFAP 显着高于 ACI（对于＜1 小时和＜3 小时的院前样本和＜3 小时的二次样本，P < 0.001），而总 tau 显示没有组间差异。HS 患者的 2 个非常早期样本之间的院前 GFAP 释放率（pg/mL/分钟）显着高于 ACI [2.4 (0.6–14.1)] 与 0.3 (-0.3–0.9) pg/mL/分钟， P＜0.001。对于院前采样 <3 小时 (ACI n = 178, HS n = 59) 的病例，综合规则 (院前 GFAP > 410 pg/mL，或院前 GFAP 90–410 pg/mL 连同 GFAP 释放 > 0.6 pg/mL/分钟）能够在 68% 的 ACI 患者中以高确定性（NPV 98.4%）排除 HS（对 HS 的敏感性 96.6%，特异性 68%，PPV 50%）。结论 与单点测量相比，监测院前 GFAP 释放率可改善卒中亚型的超早期分化。通过连续测量，GFAP 有可能改善未来的院前卒中诊断。