Background: Some patients do poorly despite small infarcts after endovascular therapy(EVT) whilst others with large infarcts do well. We validated exploratory findings from the ESCAPE trial regarding factors associated with such discrepancies, in the ESCAPE-NA1 trial(NCT02930018). Methods: We identified “discrepant cases” with modified Rankin Scale(mRS)≥3 despite small follow-up infarct volume(FIV≤25th-percentile) on 24-hour CT/MRI or mRS≤2 despite large FIV(volume≥75th-percentile). We compared area-under-the-curve(AUC) of pre-specified logistic models containing (a)pre-treatment factors(age/cancer/vascular risk-factors) and (b)treatment-related/post-treatment factors(serious adverse events/SAEs) in identifying small-FIV/mRS≥3 and large-FIV/mRS≤2, with stepwise regression-derived models. Results: Among 1,091 patients, 42/287(14.6%) with FIV≤7mL(25th-percentile) had mRS≥3; 65/275(23.6%) with FIV≥92mL(75th-percentile) had mRS≤2. Pre-specified pre-treatment factors(age/cancer/vascular risk-factors) were associated with FIV≤7mL/mRS≥3; stepwise models selected similar variables(similar AUCs:0.92-0.93,p=0.42). SAEs(infarct-in-new-territory/recurrent stroke/pneumonia/heart failure) were strongly associated with FIV≤7mL/mRS≥3; stepwise models also identified onset-to-needle time and hemoglobin(24-hours) as treatment-related/post-treatment factors(similar AUCs:0.92-0.94,p=0.14). Younger age was associated with FIV≥92mL/mRS≤2; stepwise models also selected diabetes absence and baseline hemoglobin(similar AUCs:0.76-0.77,p=0.82). Absence of SAEs(stroke progression/pneumonia/intracerebral hemorrhage) was strongly associated with FIV≥92mL/mRS≤2; stepwise models also identified 24-hour hemoglobin, glucose, and BP(similar AUCs:0.79-0.80,p=0.030). Conclusions: FIV-mRS discrepancies are associated with pre-treatment factors like age/comorbidities; and post-treatment complications related to stroke evolution, secondary prevention, and post-acute care quality. Optimizing thrombolysis speed, BP, glucose, and hemoglobin are modifiable factors meriting further study.

Background: Decisions to treat large-vessel occlusion with endovascular therapy(EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients’ pre-stroke comorbidities. Methods: In an international survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case-scenarios. Five included comorbidities(metastatic/non-metastatic cancer, cardiac/respiratory/renal disease, non-disabling/mild cognitive impairment[MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions. Results: Among 607 physicians(38 countries), EVT was favoured in 1,097/1,379(79.6%) responses for comorbidity-related scenarios under current resources versus 1,510/1,657(91.1%,OR:0.38, 95%CI.0.31-0.47) for six “level-1A” scenarios (assuming ideal conditions:82.7% vs 95.1%,OR:0.25,0.19-0.33). However, this was reversed on including all other scenarios(e.g. under current resources:3,489/4,691[74.4%], OR:1.34,1.17-1.54). Responses favouring alteplase for comorbidity-related(e.g.75.0% under current resources) scenarios were comparable to level-1A scenarios(72.2%) and higher than all others(60.4%). No comorbidity-related factor independently diminished EVT-odds. MCI and dependence carried higher alteplase-odds; cancer and cardiac/respiratory/renal disease had lower odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT, lower alteplase-odds), practicing in East-Asia (higher EVT-odds), and in interventional neuroradiology(lower alteplase-odds vs neurology). Conclusions: Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT.

Background: Thrombus embolization during endovascular treatment (EVT) occurs in up to 9% of cases, making secondary medium-vessel occlusions (MeVOs) of particular interest to neurointerventionalists. We sought to gain insight into the current EVT approaches for secondary MeVO stroke in an international case-based survey as there are currently no clear recommendations for EVT in these patients. Methods: Participants were presented with three secondary MeVO cases, each consisting of three case-vignettes with changes in patient neurological status (improvement, no change, unable to assess). Clustered multivariable logistic regression analyses were used to assess factors influencing the decision to treat. Results: 366 physicians from 44 countries took part. The majority (54.1%) were in favor of EVT. Participants were more likely to treat occlusions in the anterior M2/3 (74.3%; risk ratio [RR]2.62, 95%CI:2.27-3.03) or A3 (59.7%; RR2.11, 95%CI:1.83-2.42) segment, compared to the M3/4 segment (28.3%;reference). Physicians were less likely to pursue EVT in patients with neurological improvement (49.9% versus 57.0%; RR0.88, 95%CI:0.83-0.92). Interventionalists and more experienced physicians were more likely to treat secondary MeVOs. Conclusions: Physician’s willingness to treat secondary MeVOs endovascularly is limited and varies per occlusion location and change in neurological status. More evidence on the safety and efficacy of EVT for secondary MeVO stroke is needed.

Background: Small brain infarcts are often seen on diffusion-weighted MRI(DWI) following surgical/endovascular procedures. Little is known about their clinical effects. We examined the association of iatrogenic infarcts with outcomes in the ENACT(Evaluating Neuroprotection in Aneurysm Coiling Therapy) trial of nerinetide in endovascular aneurysm repair. Methods: In this post-hoc analysis, we used multi-variable models to evaluate the association of presence/number of DWI iatrogenic infarcts with NIHSS(National Institutes of Health Stroke Scale), mRS(modified Rankin Scale), and cognitive/neuropsychological scores(30-minute battery) at 1-4 and 30-days post-procedure. We also related infarct number to a Z-score-derived composite outcome score(quantile regression). Results: Among 185 patients(median age:56,IQR:50-64), 124(67.0%) had iatrogenic infarcts(median:4,IQR:2-10.5). Nerinetide resulted in fewer infarcts. Patients with infarcts had lower Mini-Mental State Exam(MMSE) scores at 2-4 days(median:28 vs 29, adjusted-coefficient[acoef] per additional infarct:-1.11,95%CI:-1.88 to -0.34,p=0.005). Infarct number was associated with worse day-1 NIHSS(aOR for NIHSS≥1:1.07,1.02-1.12,p=0.009), day 2-4 mRS(adjusted common odds-ratio[aOR]:1.05,1.01-1.09,p=0.005) and MMSE(acoef:-0.07,-0.13 to -0.003,p=0.040), 30-day mRS(aOR:1.04,1.01-1.07,p=0.016) and Hopkins Verbal Learning Test scores(acoef:-0.21,-0.39 to -0.03,p=0.020), as well as worse composite scores at 1-4 and 30-days(acoef:-0.09,-0.15 to -0.03,p=0.006). Conclusions: Iatrogenic infarcts were associated with subtle differences in post-procedural(1-4 days) and 30-day outcomes in this middle-aged cohort. Future studies should use batteries of similar/greater granularity to validate optimal measures for short- versus long-term manifestations.

Background: There are no recommendations regarding endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to primary medium vessel occlusion (MeVO). The aim of this study was to examine the willingness to perform EVT among stroke physicians in patients with mild, yet personally-disabling deficits due to MeVO. Methods: In an international survey consisting of 4 cases of primary MeVOs, participants were asked whether the presence of personally-disabling deficits would influence their decision-making for EVT despite the patients having low NIHSS scores. Decision rates were calculated based on physician characteristics. Clustered univariable logistic regression was performed. Results: 366 participants from 44 countries provided 2562 answers. 56.9% opted to perform EVT in scenarios in which the deficit was relevant to the patient’s profession versus 41.0% in which no information regarding patient profession was provided (RR1.39, p<0.001). The largest effect sizes were seen for female participants (RR1.68, 95%CI:1.35-2.09), participants >60 years (RR1.61, 95%CI:1.23-2.10), with more neurointervention experience (RR1.60, 95%CI:1.24-2.06), and who personally performed >100 EVTs per year (RR1.63, 95%CI:1.22-2.17). Conclusions: The presence of a patient-relevant deficit in low NIHSS AIS due to MeVO is an important factor for EVT decision-making. This may have relevance for the conduct and interpretation of low NIHSS EVT randomized trials.