Incidence, Associations, and Mechanisms of Unexplained Early Neurologic Deterioration After Thrombectomy in Stroke Patients

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.