Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Portugal (D.F., J.N., R.D.).
Department of Neurology (D.F., M.M., R.D., E.A., P.C.), Centro Hospitalar Universitário de São João, Porto, Portugal.
Stroke. 2021 Mar;52(3):859-867. doi: 10.1161/STROKEAHA.120.032130. Epub 2021 Feb 1.
The mechanisms linking systemic inflammation to poor outcome in ischemic stroke are not fully understood. The authors investigated if peripheral inflammation following reperfusion therapy leads to an increase in cerebral edema (CED), thus hindering the clinical recovery.
We designed a single-center study conducted at Centro Hospitalar Universitário São João between 2017 and 2019. Inclusion criteria were being adult, having an anterior circulation acute ischemic stroke, and receiving reperfusion therapy. Neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios, and the systemic inflammatory response syndrome criteria were determined. The presence and grade of CED were evaluated on the computed tomography performed 24 hours following event. The clinical outcomes included early neurological deterioration and functional dependence at 90 days. Adjusted odds ratio and 95% CI were obtained by ordinal and logistic regression models. Optimal cutoff values were defined using receiver operating characteristic analysis in the training cohort and validated in an independent data set.
Five hundred fifty-three patients were included. Neutrophil-to-lymphocyte increased with higher degrees of CED at 24 hours (adjusted odds ratio, 1.34 [1.09-1.68], <0.01) and was associated with early neurological deterioration (adjusted odds ratio, 1.30 [1.04-1.63], <0.05) and poor functional status at 90 days (adjusted odds ratio, 1.79 [1.28-2.48], <0.01). Platelet-to-lymphocyte was not associated with the outcomes. Systemic inflammatory response syndrome was related to CED due to altered white blood cell counts. Neutrophil-to-lymphocyte was the best predictor with an area under the curve around 0.7. Neutrophil-to-lymphocyte ≥7 had and accuracy, sensitivity, and specificity around 60%.
Increased systemic inflammation is linked to the severity of CED early after reperfusion therapy in stroke. Easily obtained inflammatory markers convey early warning alerts for patients at risk of severe neurological complications with an impact on long-term functional outcome. CED quantification should be included as an end point in proof-of-concept trials in immunomodulation in stroke.
目前尚不完全清楚全身炎症与缺血性脑卒中不良预后之间的关联机制。本研究旨在探讨再灌注治疗后外周炎症是否会导致脑水肿（CED）增加，从而阻碍临床康复。
本研究为单中心研究，于 2017 年至 2019 年在 Centro Hospitalar Universitário São João 进行。纳入标准为：成年患者、急性前循环缺血性脑卒中、接受再灌注治疗。检测中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值和全身炎症反应综合征标准。发病 24 小时内行颅脑计算机断层扫描（CT）评估 CED 发生情况和严重程度。临床结局包括：发病 24 小时内发生早期神经功能恶化和 90 天功能依赖。采用有序和逻辑回归模型计算调整后的比值比（OR）及其 95%置信区间（CI）。在训练队列中采用受试者工作特征（ROC）曲线分析确定最佳截断值，并在独立数据集进行验证。
共纳入 553 例患者。发病 24 小时时，随着 CED 程度的增加，中性粒细胞与淋巴细胞比值逐渐升高（调整 OR，1.34[1.09-1.68]，<0.01），且与早期神经功能恶化（调整 OR，1.30[1.04-1.63]，<0.05）和 90 天功能不良（调整 OR，1.79[1.28-2.48]，<0.01）相关。血小板与淋巴细胞比值与结局无关。全身炎症反应综合征与白细胞计数改变引起的 CED 相关。中性粒细胞与淋巴细胞比值是最佳预测指标，ROC 曲线下面积约为 0.7。中性粒细胞与淋巴细胞比值≥7 的准确率、灵敏度和特异度均约为 60%。
再灌注治疗后，全身炎症与 CED 严重程度增加相关。易于获得的炎症标志物可对发生严重神经并发症风险较高的患者发出早期预警，对长期功能结局产生影响。在脑卒中免疫调节的概念验证试验中，应将 CED 量化作为终点纳入研究。
