Pensato Umberto, Coutts Shelagh B, van Adel Brain, Chapot Rene, Puetz Volker, Demchuk Andrew, Goyal Mayank, Hill Michael D, Ospel Johanna Maria
IRCCS Humanitas Research Hospital, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Milan, Italy.
Neurology. 2025 Aug 26;105(4):e213945. doi: 10.1212/WNL.0000000000213945. Epub 2025 Jul 30.
Early neurologic deterioration (END) in ischemic stroke after endovascular thrombectomy (EVT) is a frequent complication that remains unexplained in most cases. We aimed to explore the incidence of, and associated variables with, unexplained END (unEND).
This is a post hoc analysis of the ESCAPE-NA1 trial, a double-blind, multicentric, randomized clinical trial evaluating nerinetide vs placebo in adult ischemic stroke patients with anterior circulation large vessel occlusion treated with EVT. END was defined as an increase of ≥4 points in the NIH Stroke Scale score between baseline or 2-6 hours after EVT (whichever was the lowest) and 24-hour assessment. The primary outcome was unEND, defined as END without associated hemorrhagic or thrombotic/thromboembolic events. Backward stepwise multivariable logistic regression was used to identify baseline variables independently associated with unEND. In the CT perfusion (CTP) subgroup, regression analysis adjusted for baseline covariates was used to assess the association between unEND and infarct extension beyond the penumbra (IEBP), defined as a follow-up infarct volume larger by at least 10 mL than the initial critically hypoperfused tissue volume (time-to-maximum >6-second volume).
Overall, 1063 patients were included in this study; the median age was 70.8 years (interquartile range 60.7-79.7), and 526 (49.5%) were women. Among them, 172 (16.2%) experienced END: 20 (11.6%) had an associated thrombotic/thromboembolic event, 27 (15.7%) had an associated hemorrhagic event, 8 (4.7%) had both associated thrombotic/thromboembolic and hemorrhagic events, and 117 (68.0%) had an unEND (overall incidence of unEND = 11.0%). Variables independently associated with unEND were anesthesia use (adjusted odds ratio [aOR] 7.23, 95% CI 4.63-11.30), age (aOR 1.02, 95% CI 1.01-1.04 per 1-year increase), and onset-to-reperfusion time (aOR 1.02, 95% CI 1.01-1.03 per 10-minute increase). In patients with available baseline CTP (n = 410), unEND was associated with the presence of IEBP (OR 6.81, 95% CI 2.58-18.01) and larger IEBP volume (OR 1.07, 95% CI 1.01-1.13 per 10-mL increase).
UnEND occurred in approximately 10% of large vessel occlusion thrombectomy patients and was associated with older age, longer onset-to-reperfusion time, and anesthesia use. Patients who experienced IEBP, that is, 24-hour infarct volume extension beyond the initial hypoperfused tissue, were 7 times more likely to develop unEND.
血管内血栓切除术（EVT）治疗缺血性卒中后的早期神经功能恶化（END）是一种常见并发症，多数情况下其病因不明。我们旨在探讨不明原因的END（unEND）的发生率及相关变量。
这是对ESCAPE-NA1试验的事后分析，该试验是一项双盲、多中心、随机临床试验，评估在接受EVT治疗的前循环大血管闭塞成年缺血性卒中患者中，神经保护剂与安慰剂的疗效。END定义为在基线或EVT后2至6小时（取较低值）至24小时评估期间，美国国立卫生研究院卒中量表（NIHSS）评分增加≥4分。主要结局为unEND，定义为无相关出血或血栓形成/血栓栓塞事件的END。采用向后逐步多变量逻辑回归分析来确定与unEND独立相关的基线变量。在CT灌注（CTP）亚组中，采用经基线协变量调整的回归分析来评估unEND与梗死灶超出半暗带范围（IEBP）的相关性，IEBP定义为随访梗死体积比初始严重灌注不足组织体积（最大密度时间>6秒时的体积）至少大10 mL。
总体而言，本研究纳入了1063例患者；中位年龄为70.8岁（四分位间距60.7 - 79.7），526例（49.5%）为女性。其中，172例（16.2%）发生END：20例（11.6%）伴有血栓形成/血栓栓塞事件，27例（15.7%）伴有出血事件，8例（4.7%）同时伴有血栓形成/血栓栓塞和出血事件，117例（68.0%）发生unEND（unEND总体发生率 = 11.0%）。与unEND独立相关的变量包括麻醉使用（调整后的优势比[aOR] 7.23，95%置信区间[CI] 4.63 - 11.30）、年龄（每增加1岁，aOR 1.02，95% CI 1.01 - 1.04）以及发病至再灌注时间（每增加10分钟，aOR
