NoNO (Canada)

Background: Sex differences have been observed in functional outcomes after endovascular thrombectomy (EVT). Brain frailty markers like atrophy and small vessel disease burden have been shown to be associated with EVT outcomes. We aimed to investigate the association between imaging markers of brain frailty and functional outcomes after EVT in women and men. Methods: This study is a post hoc analysis of the ESCAPE-NA1 trial that evaluated the efficacy and safety of nerinetide in patients with large vessel occlusion receiving EVT within 12 hours of onset. Baseline CT was used to assess brain frailty markers including atrophy score, inter-caudate distance to inner table width ratio [CC/IT ratio]), white matter disease (Fazekas score), presence of lacunes and old infarctions, and follow-up MRI was used to assess microbleed and lacunes burden. Outcomes included the modified Rankin Scale (mRS) at 90 days (dichotomized as 0-2 vs 3-6, and ordinal/shift analysis). Multivariable logistic regression models were used to examine the association between imaging frailty measures and 90-day mRS separately in women and men. Results: A total of 1,102 participants (mean age 69.5 ± 13.7 years, 548 women) were analyzed. Women were older (74 vs. 69 years, p<0.0001), less likely to smoke (38% vs. 60%, p<0.0001), and had a lower baseline NIHSS (16 [12–21] vs. 17 [13–21], p=0.009), compared to men. Regarding imaging frailty measures, women had a lower CC/IT ratio (0.12 [0.09–0.15] vs. 0.13 [0.10–0.15], p=0.01), a higher Fazekas score (1 [0–2] vs. 0 [0–2], p<0.0001), and more frequent lacunes (27% vs. 22%, p=0.04). In the multivariable analyses, imaging frailty measures were generally associated with worse outcomes at 90-days; however, significant associations between these markers and 90-day mRS were observed only in women and not in men. CT-based markers such as cortical and subcortical atrophy, CC/IT ratio, old infarction carried significantly lower odds of 90-day mRS 0-2 in women but not men (Figure 1). Similar findings were also seen on shift analyses of the mRS. However, there were no statistically significant interactions by sex for these brain frailty measures. Conclusion: In this cohort of EVT recipients, significant associations between imaging brain frailty measures and 90-day outcomes were seen only in women and not in men. These findings merit validation in other cohorts as they suggest sex differences in the effects of brain frailty on post-stroke outcomes.

Predicting outcome after endovascular treatment for acute ischemic stroke is challenging. We aim to investigate differences between predicted and observed outcomes in patients with acute ischemic stroke treated with endovascular treatment and to evaluate the performance of a validated outcome prediction score. MR PREDICTS is an outcome prediction tool based on a logistic regression model designed to predict the treatment benefit of endovascular treatment based on the MR CLEAN and HERMES populations. ESCAPE-NA1 is a randomized trial of nerinetide vs. placebo in patients with acute stroke and large vessel occlusion. We applied MR PREDICTS to patients in the control arm of ESCAPE-NA1. Model performance was assessed by calculating its discriminative ability and calibration. Overall, 556/1105 patients (50.3%) in the ESCAPE-NA1-trial were randomized to the control arm, 435/556 (78.2%) were treated within 6 h of symptom onset. Good outcome (modified Rankin scale 0-2) at 3 months was achieved in 275/435 patients (63.2%), the predicted probability of good outcome was 52.5%. Baseline characteristics were similar in the study and model derivation cohort except for age (ESCAPE-NA1: mean: 70 y vs. HERMES: 66 y), hypertension (72% vs. 57%), and collaterals (good collaterals, 15% vs. 44%). Compared to HERMES we observed higher rates of successful reperfusion (TICI 2b-3, ESCAPE-NA1: 87% vs. HERMES: 71%) and faster times from symptom onset to reperfusion (median: 201 min vs. 286 min). Model performance was good, indicated by a c-statistic of 0.76 (95%confidence interval: 0.71-0.81). Outcome-prediction using models created from HERMES data, based on information available in the emergency department underestimated the actual outcome in patients with acute ischemic stroke and large vessel occlusion receiving endovascular treatment despite overall good model performance, which might be explained by differences in quality of and time to reperfusion. These findings underline the importance of timely and successful reperfusion for functional outcomes in acute stroke patients.

Although reperfusion is associated with improved outcomes in patients with acute ischemic stroke undergoing endovascular treatment, many patients still do poorly. We investigated whether CTP modifies the effect of near-complete reperfusion on clinical outcomes, ie, whether poor clinical outcomes despite near-complete reperfusion can be partly or fully explained by CTP findings. Data are from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial. Admission CTP was processed using RAPID software, generating relative CBF and CBV volume maps at standard thresholds. CTP lesion volumes were compared in patients with-versus-without near-complete reperfusion. Associations between each CTP metric and clinical outcome (90-day mRS) were tested using multivariable logistic regression, adjusted for baseline imaging and clinical variables. Treatment-effect modification was assessed by introducing CTP lesion volume × reperfusion interaction terms in the models. CTP lesion volumes and reperfusion status were available in 410/1105 patients. CTP lesion volumes were overall larger in patients without near-complete reperfusion, albeit not always statistically significant. Increased CBF <34%, CBV <34%, CBV <38%, and CBV <42% lesion volumes were associated with worse clinical outcome (ordinal mRS) at 90 days. CTP core lesion volumes did not modify the treatment effect of near-complete recanalization on clinical outcome. CTP did not modify the effect of near-complete reperfusion on clinical outcomes. Thus, CTP cannot explain why some patients with near-complete reperfusion have poor clinical outcomes.

IntroductionIt remains unclear whether incomplete reperfusion caused by multiple small occlusions or slow flow after mechanical thrombectomy (MT) results in infarction on follow-up imaging.1AimWe investigated whether small peripheral thrombi or slow flow was associated with infarction on follow-up scan.MethodsPatients from the ESCAPE-NA1 trial with final reperfusion grade eTICI 2b were analysed. Residual/peripheral occlusions were evaluated on the final DSA run. Patients with multiple small non-MT-accessible occlusions (clear marked filling defects representing the peripheral thrombus edge (meniscus sign)) or slow flow (gradual stagnation of flow) or both (mixed pattern) were included. Established infarct within the incomplete reperfusion territory was retrospectively reviewed on baseline non-contrast CT to distinguish slow flow through infarcted brain. New infarct in the incomplete reperfusion territory was assessed on follow-up CT/MR.ResultsOf 1105 ESCAPE-NA1 patients, 443 with final eTICI 2b reperfusion were included (40.1%). Of these, 260 had multiple small non-MT-accessible occlusions. Meniscus sign was detected in 26/260 (10%) cases, slow flow in 156/260 (60%) and mixed pattern in 78/260 (30%). 47/260 cases (18.1%) had an established infarct on baseline imaging. Of the remaining 213 cases, IR resulted in infarction in 114 cases (43.9%); of which, meniscus sign was seen in 16/114 cases (14%) and mixed pattern in 42/114 cases (36.8%).ConclusionThe majority of incomplete reperfusion caused by multiple small occlusions or slow flow was associated with new infarction on follow-up imaging. In half of these cases, distal occlusions (meniscus sign) were detected, which could be potential targets for intra-arterial thrombolysis.ReferencesKaesmacher J, Ospel JM, Meinel TR, et al. Thrombolysis un Cerebral Infarction 2b Reperfusions. Stroke. September 2020.Do you have any conflict of interest to declare?: No

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