Wang W, Jia Q, Wang S B, Li X D, Fan Y M
Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300350, China.
Zhonghua Wai Ke Za Zhi. 2024 May 1;62(5):443-451. doi: 10.3760/cma.j.cn112139-20230926-00144.
To explore the clinical characteristics of neutrophil extracellular trap (NET) in patients with severe cerebral venous sinus thrombosis (CVST) and to study their prognostic value in the acute and subacute phases. This study is a retrospective case series analysis. Clinical and pathological data of 52 patients with severe cerebral venous sinus thrombosis who underwent endovascular treatment in the Department of Neurosurgery, Tianjin Huanhu Hospital from June 2019 to June 2022 were retrospectively analyzed. There were 20 males and 32 females, with an age of (40.1±13.6) years(range:18 to 66 years). Forty-five healthy physical examinees were included in the control group. High-resolution MRI was used to stage the thrombus, with 11 cases in the acute group, 28 cases in the subacute group, and 13 cases in the chronic group. Thrombus specimens were obtained through endovascular treatment, and the fluorescence intensity of NET in peripheral blood at different time points was analyzed by immunofluorescence contrast,including the double-stranded DNA structure and adhesion protein components (citrolinated histone H3 (CitH3), myeloperoxidase-DNA complex(MPO-DNA), neutrophil elastase (NE)). The NET markers were determined by ELISA. Spearman rank correlation analysis was used to analyze the correlation between the NET markers in peripheral blood of patients with severe cerebral venous sinus thrombosis in the acute and subacute phases and the volume of venous sinus thrombus, the degree of venous sinus recanalization after treatment, and the discharge modified Rankin scale(mRS)score. The accuracy of NET markers in predicting the prognosis of patients with severe cerebral venous sinus thrombosis was analyzed by drawing receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). The results of immunofluorescence staining and ELISA showed that no NET structure was formed in the peripheral blood of the control group, while CitH3, MPO-DNA and NE levels in the peripheral blood of CVST patients were increased, among which the acute stage group was the highest, followed by the subacute group, and the chronic group was the lowest. Spearman correlation analysis showed that CitH3, MPO-DNA and NE levels in peripheral blood of patients in acute group and subacute group were positively correlated with thrombus volume and mRS score at discharge (<0.05). The levels of CitH3 and MPO-DNA in peripheral blood of patients with complete venous sinus recanalization were lower than those of patients with partial venous sinus recanalization (<0.01). ROC curve analysis results showed that MPO-DNA and NE had no predictive ability for the prognosis of CVST patients ( values were 0.614 and 0.324, respectively), and the AUC of CitH3 was 0.800 (95%: 0.638~0.962, =0.032), the best cut-off value was 13.5 μg/L, the sensitivity was 100%, and the specificity was 58.8%. A large number of NET are formed in patients with severe cerebral venous sinus thrombosis in acute stage. Patients with severe cerebral venous sinus thrombosis in acute stage and subacute stage with high peripheral blood NET content has a low rate of complete sinus revascularization and poor neurological function recovery after treatment.
探讨重症脑静脉窦血栓形成(CVST)患者中性粒细胞胞外陷阱(NET)的临床特征,并研究其在急性期和亚急性期的预后价值。本研究为回顾性病例系列分析。回顾性分析2019年6月至2022年6月在天津环湖医院神经外科接受血管内治疗的52例重症脑静脉窦血栓形成患者的临床和病理资料。其中男性20例,女性32例,年龄(40.1±13.6)岁(范围:18至66岁)。对照组纳入45名健康体检者。采用高分辨率MRI对血栓进行分期,急性组11例,亚急性组28例,慢性组13例。通过血管内治疗获取血栓标本,采用免疫荧光对比分析不同时间点外周血中NET的荧光强度,包括双链DNA结构和黏附蛋白成分(瓜氨酸化组蛋白H3(CitH3)、髓过氧化物酶-DNA复合物(MPO-DNA)、中性粒细胞弹性蛋白酶(NE))。采用酶联免疫吸附测定(ELISA)法测定NET标志物。采用Spearman等级相关分析分析急性期和亚急性期重症脑静脉窦血栓形成患者外周血中NET标志物与静脉窦血栓体积、治疗后静脉窦再通程度及出院时改良Rankin量表(mRS)评分之间的相关性。通过绘制受试者工作特征(ROC)曲线并计算曲线下面积(AUC)分析NET标志物对重症脑静脉窦血栓形成患者预后的预测准确性。免疫荧光染色和ELISA结果显示,对照组外周血未形成NET结构;CVST患者外周血中CitH3、MPO-DNA和NE水平升高,其中急性期组最高,其次为亚急性期组,慢性期组最低。Spearman相关性分析显示,急性组和亚急性组患者外周血中CitH3、MPO-DNA和NE水平与血栓体积及出院时mRS评分呈正相关(<0.05)。静脉窦完全再通患者外周血中CitH3和MPO-DNA水平低于部分静脉窦再通患者(<0.01)。ROC曲线分析结果显示,MPO-DNA和NE对CVST患者预后无预测能力(值分别为0.614和0.324),CitH3的AUC为0.800(95%:0.638~0.962,=0.032),最佳截断值为13.5μg/L,灵敏度为100%,特异度为58.8%。重症脑静脉窦血栓形成急性期患者大量形成NET。急性期和亚急性期外周血NET含量高的重症脑静脉窦血栓形成患者静脉窦完全再通率低,治疗后神经功能恢复差。