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Abstract：
BACKGROUND: Rapid disease progression in neuroemergencies is associated with blood-brain barrier (BBB) disruption. We investigated a less invasive strategy for assessing BBB status by evaluating S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) at early stages of the hypoxic-ischemic brain injury (HIBI) cascade.
METHODS: This retrospective study used prospectively collected data from patients with out-of-hospital cardiac arrest (August 2019-July 2021). Albumin specimens obtained from serum and cerebrospinal fluid via arterial catheter and lumbar puncture were used to measure the albumin quotient (Qa), which is widely accepted as the gold standard method for detecting BBB disruption. Serum S100B and NSE levels were measured simultaneously following the return of spontaneous circulation. We conducted linear regression to evaluate the relationship between S100B and Qa and the predictive performance of S100B for abnormal Qa. The primary study outcome was abnormal Qa (>0.007).
RESULTS: Forty-one patients were enrolled; 30 showed an abnormal Qa suggestive of BBB disruption. S100B levels were significantly higher than in those with a normal Qa (0.244 μg/L [interquartile range [IQR], 0.146-0.823 vs 0.754 μg/L [IQR, 0.317-2.228], P = .03). We report a positive correlation between serum S100B and Qa (R2 = 0.110; P = .04). The area under the receiver operating characteristics curve (AUROC) evaluating the predictive performance of S100B with respect to abnormal Qa was 0.718 (95% confidence interval, 0.556-0.847). The cutoff value for S100B (with respect to BBB disruption) in the total cohort was 0.283 μg/L (sensitivity, 80.0%; specificity, 72.7%). Subgroup analyses in patients with serum neuron-specific enolase (NSE) levels of <40.8 ng/mL (excluding those with established neuronal cell injury) showed an improved correlation coefficient (R2 = 0.382; P < .01) and predictive performance (AUROC, 0.836 [95% confidence interval, 0.629-0.954]) compared with the total cohort.
CONCLUSIONS: Serum S100B obtained at an early stage of the HIBI cascade is associated with abnormal Qa, suggesting BBB disruption. The predictive performance of S100B and the correlation between serum S100B and Qa can be improved using a complementary strategy (i.e., evaluations of S100B and NSE levels) that combines considerations of cell damage in astrocytes and neurons.
METHODS: This retrospective study used prospectively collected data from patients with out-of-hospital cardiac arrest (August 2019-July 2021). Albumin specimens obtained from serum and cerebrospinal fluid via arterial catheter and lumbar puncture were used to measure the albumin quotient (Qa), which is widely accepted as the gold standard method for detecting BBB disruption. Serum S100B and NSE levels were measured simultaneously following the return of spontaneous circulation. We conducted linear regression to evaluate the relationship between S100B and Qa and the predictive performance of S100B for abnormal Qa. The primary study outcome was abnormal Qa (>0.007).
RESULTS: Forty-one patients were enrolled; 30 showed an abnormal Qa suggestive of BBB disruption. S100B levels were significantly higher than in those with a normal Qa (0.244 μg/L [interquartile range [IQR], 0.146-0.823 vs 0.754 μg/L [IQR, 0.317-2.228], P = .03). We report a positive correlation between serum S100B and Qa (R2 = 0.110; P = .04). The area under the receiver operating characteristics curve (AUROC) evaluating the predictive performance of S100B with respect to abnormal Qa was 0.718 (95% confidence interval, 0.556-0.847). The cutoff value for S100B (with respect to BBB disruption) in the total cohort was 0.283 μg/L (sensitivity, 80.0%; specificity, 72.7%). Subgroup analyses in patients with serum neuron-specific enolase (NSE) levels of <40.8 ng/mL (excluding those with established neuronal cell injury) showed an improved correlation coefficient (R2 = 0.382; P < .01) and predictive performance (AUROC, 0.836 [95% confidence interval, 0.629-0.954]) compared with the total cohort.
CONCLUSIONS: Serum S100B obtained at an early stage of the HIBI cascade is associated with abnormal Qa, suggesting BBB disruption. The predictive performance of S100B and the correlation between serum S100B and Qa can be improved using a complementary strategy (i.e., evaluations of S100B and NSE levels) that combines considerations of cell damage in astrocytes and neurons.
摘要：
背景：神经急症的快速疾病进展与血脑屏障（BBB）破坏有关。我们通过评估缺氧缺血性脑损伤（HIBI）级联反应早期的S100钙结合蛋白B（S100B）和神经元特异性烯醇化酶（NSE），研究了一种侵入性较小的评估BBB状态的策略。
方法：这项回顾性研究使用了来自院外心脏骤停患者（2019年8月至2021年7月）的前瞻性数据。通过动脉导管和腰椎穿刺从血清和脑脊液中获得的白蛋白标本用于测量白蛋白商（Qa）。被广泛认为是检测BBB破坏的金标准方法。自发循环恢复后，同时测量血清S100B和NSE水平。我们进行了线性回归，以评估S100B和Qa之间的关系以及S100B对异常Qa的预测性能。主要研究结果为Qa异常(>0.007)。
结果：纳入41例患者；30例患者Qa异常提示BBB破坏。S100B水平显着高于Qa正常的那些（0.244μg/L[四分位距[IQR]，0.146-0.823vs0.754μg/L[IQR，0.317-2.228],P=.03）。我们报告血清S100B和Qa之间呈正相关（R2=0.110；P=0.04）。评估S100B相对于异常Qa的预测性能的受试者工作特征曲线下面积（AUROC）为0.718（95％置信区间，0.556-0.847)。整个队列中S100B（相对于BBB破坏）的截止值为0.283μg/L（敏感性，80.0%；特异性，72.7%）。血清神经元特异性烯醇化酶（NSE）水平<40.8ng/mL（不包括已确定的神经元细胞损伤）的患者的亚组分析显示出改善的相关系数（R2=0.382；P<0.01）和预测性能（AUROC，0.836[95%置信区间，0.629-0.954])与总队列相比。
结论：在HIBI级联的早期阶段获得的血清S100B与异常Qa有关，提示BBB中断。S100B的预测性能以及血清S100B和Qa之间的相关性可以使用互补策略（即，S100B和NSE水平的评估），结合了星形胶质细胞和神经元细胞损伤的考虑。
方法：这项回顾性研究使用了来自院外心脏骤停患者（2019年8月至2021年7月）的前瞻性数据。通过动脉导管和腰椎穿刺从血清和脑脊液中获得的白蛋白标本用于测量白蛋白商（Qa）。被广泛认为是检测BBB破坏的金标准方法。自发循环恢复后，同时测量血清S100B和NSE水平。我们进行了线性回归，以评估S100B和Qa之间的关系以及S100B对异常Qa的预测性能。主要研究结果为Qa异常(>0.007)。
结果：纳入41例患者；30例患者Qa异常提示BBB破坏。S100B水平显着高于Qa正常的那些（0.244μg/L[四分位距[IQR]，0.146-0.823vs0.754μg/L[IQR，0.317-2.228],P=.03）。我们报告血清S100B和Qa之间呈正相关（R2=0.110；P=0.04）。评估S100B相对于异常Qa的预测性能的受试者工作特征曲线下面积（AUROC）为0.718（95％置信区间，0.556-0.847)。整个队列中S100B（相对于BBB破坏）的截止值为0.283μg/L（敏感性，80.0%；特异性，72.7%）。血清神经元特异性烯醇化酶（NSE）水平<40.8ng/mL（不包括已确定的神经元细胞损伤）的患者的亚组分析显示出改善的相关系数（R2=0.382；P<0.01）和预测性能（AUROC，0.836[95%置信区间，0.629-0.954])与总队列相比。
结论：在HIBI级联的早期阶段获得的血清S100B与异常Qa有关，提示BBB中断。S100B的预测性能以及血清S100B和Qa之间的相关性可以使用互补策略（即，S100B和NSE水平的评估），结合了星形胶质细胞和神经元细胞损伤的考虑。
