Jeon So-Young, Kang Changshin, You Yenho, Park Jung Soo, Min Jin Hgon, Jeong Wonjoon, Ryu Hyun Shik, Choi Jiyoung, Lee Byung Kook
Department of Emergency Medicine, College of Medicine, Chungnam National University, 266 Munwha-ro, Jung-gu, Daejeon, 35015, Republic of Korea.
Department of Emergency Medicine, Chungnam National University Hospital, Daejoen, Republic of Korea.
Crit Care. 2025 Aug 4;29(1):342. doi: 10.1186/s13054-025-05572-8.
The prognostic value of serum biomarkers after out-of-hospital cardiac arrest (OHCA) depends on timing, but the physiological basis remains unclear. We investigated whether blood-brain barrier (BBB) integrity and biomarker-specific properties explain the time-dependent differences in prognostic performance.
This retrospective study included comatose adult OHCA survivors who underwent paired serum and cerebrospinal fluid (CSF) measurements of neuron-specific enolase (NSE; 47 kDa) and S100 calcium-binding protein B (S100B; 21 kDa) at 0 (H0), 24 (H24), 48 (H48), and 72 (H72) h after return of spontaneous circulation. BBB disruption was assessed using the CSF/serum albumin quotient (Q). Prognostic performance was assessed using AUC analysis for 6-month poor neurological outcome (Cerebral Performance Category 3-5).
Among 111 patients (59% poor outcome), 646 serum and 620 CSF samples were analyzed. BBB disruption was more severe in the poor outcome group at all timepoints (all P < 0.001), peaking at H24 (Q 0.0282 [IQR 0.0150-0.120]) and remaining elevated at H72 (0.0228 [IQR 0.0147-0.0598]). In the poor outcome group, serum S100B levels peaked at H0 (0.80 ng/mL [IQR 0.39-2.81]) and declined despite a persistent elevation in CSF levels at or above the upper detection limit (≥ 30 ng/mL). Conversely, NSE levels progressively increased in both compartments, with serum and CSF levels increasing in parallel over time. Serum NSE concentrations showed a time-dependent improvement in prognostic accuracy, peaking at H72 (AUC 0.88), whereas S100B concentrations maintained stable performance across all timepoints (AUCs 0.79-0.85, all P > 0.4). Notably, the prognostic performance of S100B remained relatively consistent regardless of BBB disruption severity, whereas NSE showed progressively improved predictive accuracy with increased BBB disruption. Across all timepoints, CSF biomarkers-particularly S100B and NSE-showed consistently higher AUCs than serum, suggesting superior prognostic utility.
Serum NSE levels closely reflect the degree of BBB disruption and CSF levels, while S100B exhibits a transient early-phase profile, with decreased serum detectability over time, even in the presence of sustained CSF elevation or severe BBB disruption. These findings highlight the importance of interpreting biomarker kinetics across compartments and timepoints rather than relying on molecular weight or BBB status alone.
院外心脏骤停（OHCA）后血清生物标志物的预后价值取决于检测时间，但生理基础尚不清楚。我们研究了血脑屏障（BBB）完整性和生物标志物特异性特性是否能解释预后性能的时间依赖性差异。
这项回顾性研究纳入了昏迷的成年OHCA幸存者，他们在自主循环恢复后的0（H0）、24（H24）、48（H48）和72（H72）小时接受了神经元特异性烯醇化酶（NSE；47 kDa）和S100钙结合蛋白B（S100B；21 kDa）的配对血清和脑脊液（CSF）检测。使用脑脊液/血清白蛋白商（Q）评估血脑屏障破坏情况。使用AUC分析评估6个月时神经功能不良预后（脑功能类别3 - 5）的预后性能。
在111例患者（59%预后不良）中，分析了646份血清样本和620份脑脊液样本。在所有时间点，预后不良组的血脑屏障破坏都更严重（所有P < 0.001），在H24时达到峰值（Q 0.0282 [IQR 0.0150 - 0.120]），并在H72时仍保持升高（0.0228 [IQR 0.0147 - 0.0598]）。在预后不良组中，血清S100B水平在H0时达到峰值（0.80 ng/mL [IQR 0.39 - 2.81]），尽管脑脊液水平持续升高至或高于检测上限（≥ 30 ng/mL），血清S100B水平仍下降。相反，两个样本中的NSE水平均逐渐升高，血清和脑脊液水平随时间平行升高。血清NSE浓度显示出预后准确性的时间依赖性改善，在H72时达到峰值（AUC 0.88），而S100B浓度在所有时间点的表现保持稳定（AUCs 0.79 - 0.85，所有P > 0.4）。值得注意的是，无论血脑屏障破坏的严重程度如何，S100B的预后性能都保持相对一致，而NSE随着血脑屏障破坏程度的增加，预测准确性逐渐提高。在所有时间点，脑脊液生物标志物——尤其是S100B和NSE——的AUC始终高于血清，表明其预后效用更佳。
血清NSE水平密切反映血脑屏障破坏程度和脑脊液水平，而S100B呈现短暂的早期特征，随着时间推移血清可检测性降低，即使脑脊液水平持续升高或血脑屏障严重破坏也是如此。这些发现强调了解释不同样本和时间点生物标志物动力学的重要性，而不是仅依赖分子量或血脑屏障状态。
