Hervella Pablo, Pérez-Mato María, Rodríguez-Yáñez Manuel, López-Dequidt Iria, Pumar José M, Sobrino Tomás, Campos Francisco, Castillo José, da Silva-Candal Andrés, Iglesias-Rey Ramón
Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, IdiPAZ, UAM, Madrid, Spain.
Front Neurol. 2021 May 11;12:652867. doi: 10.3389/fneur.2021.652867. eCollection 2021.
The purpose of this study was to investigate clinical and neuroimaging factors associated with stroke recurrence in reperfused ischemic stroke patients, as well as the influence of specific biomarkers of inflammation and endothelial dysfunction. We conducted a retrospective analysis on a prospectively registered database. Of the 875 patients eligible for this study (53.9% males; mean age 69.6 ± 11.8 years vs. 46.1% females; mean age 74.9 ± 12.6 years), 710 underwent systemic thrombolysis, 87 thrombectomy and in 78, systemic or intra-arterial thrombolysis together with thrombectomy was applied. Plasma levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) were analyzed as markers of inflammation, and soluble tumor necrosis factor-like inducer of apoptosis (sTWEAK) as an endothelial dysfunction marker. The main outcome variables of the study were the presence and severity of leukoaraiosis (LA) and stroke recurrence. The average follow-up time of the study was 25 ± 13 months, during which 127 patients (14.5%) showed stroke recurrence. The presence and severity of LA was more severe in the second stroke episode (Grade III of the Fazekas 28.3 vs. 52.8%; < 0.0001). IL-6 levels at the first admission and before reperfusion treatment in patients with and without subsequent recurrence were similar (9.9 ± 10.4 vs. 9.1 ± 7.0 pg/mL, = 0.439), but different for TNFα (14.7 ± 5.6 vs. 15.9 ± 5.7 pg/mL, = 0.031) and sTWEAK (5,970.8 ± 4,330.4 vs. 8,660.7 ± 5,119.0 pg/mL, < 0.0001). sTWEAK values ≥7,000 pg/mL determined in the first stroke were independently associated to recurrence (OR 2.79; CI 95%: 1.87-4.16, < 0.0001). The severity and the progression of LA are the main neuroimaging factors associated with stroke recurrence. Likewise, sTWEAK levels were independently associated to stroke recurrence, so further studies are necessary to investigate sTWEAK as a therapeutic target.
本研究的目的是调查再灌注缺血性中风患者中风复发相关的临床和神经影像学因素，以及炎症和内皮功能障碍的特定生物标志物的影响。我们对一个前瞻性注册数据库进行了回顾性分析。在符合本研究条件的875例患者中（男性占53.9%；平均年龄69.6±11.8岁，女性占46.1%；平均年龄74.9±12.6岁），710例接受了全身溶栓治疗，87例接受了血栓切除术，78例接受了全身或动脉内溶栓联合血栓切除术。分析了血浆白细胞介素6（IL-6）和肿瘤坏死因子α（TNFα）水平作为炎症标志物，以及可溶性肿瘤坏死因子样凋亡诱导因子（sTWEAK）作为内皮功能障碍标志物。本研究的主要结局变量是白质疏松症（LA）的存在和严重程度以及中风复发。该研究的平均随访时间为25±13个月，在此期间127例患者（14.5%）出现中风复发。LA的存在和严重程度在第二次中风发作时更为严重（Fazekas分级III级，分别为28.3%和52.8%；P<0.0001）。有或无后续复发患者首次入院时和再灌注治疗前的IL-6水平相似（9.9±10.4 vs. 9.1±7.0 pg/mL，P = 0.439），但TNFα水平不同（14.7±5.6 vs. 15.9±5.7 pg/mL，P = 0.031），sTWEAK水平也不同（5970.8±4330.4 vs. 8660.7±5119.0 pg/mL，P<0.0001）。首次中风时测定的sTWEAK值≥7000 pg/mL与复发独立相关（OR 2.79；95%CI：1.87-4.16，P<0.0001）。LA的严重程度和进展是与中风复发相关的主要神经影像学因素。同样，sTWEAK水平与中风复发独立相关，因此有必要进一步研究将sTWEAK作为治疗靶点。
