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Background and Purpose: The benefit of thrombectomy (TE) for acute ischemic stroke (AIS) in patients suffering basilar artery occlusion (BAO) is still unclear. Our aim was to analyze functional outcome after 3 months in BAO compared to anterior circulation large vessel occlusion (ACLVO) in a nationwide registry. Methods: Patients enrolled into the Austrian Endostroke Registry from 2013 to 2018 were analyzed. We used propensity score matching to control for imbalances and to compare patients with BAO and ACLVO. The primary outcome was favorable functional outcome after 3 months measured by the modified Rankin Scale (mRS) (0–2). Multivariate models were applied to estimate the effect of localization (BAO vs ACLVO). Results: In total, 2288 patients underwent TE for AIS with proximal vessel occlusion, of these 267 with BAO. Two hundred and sixty-four patients with BAO were matched to 264 patients with ACLVO. Baseline characteristics were well-balanced. The 90-day mortality did not significantly differ between patients with BAO and ACLVO. In a multivariate logistic regression model, we did not detect a significant difference in functional outcome between BAO and ACLVO (odds ratio for favorable outcome defined as mRS = 0–2: 1.19; 95% confidence interval (CI) = 0.78–1.81; p = 0.42). In patients with an onset-to-door-time ⩾270 min, TE of BAO was associated with poor functional outcome defined as mRS 3–6 (odds ratio (OR) = 3.97; 95% CI = 1.32–11.94; p = 0.01) as compared to ACLVO. Conclusion: In this study, functional outcome did not differ after TE in patients with BAO and ACLVO overall; however, we detected an association of BAO with poor outcome in patients arriving late.

Successful reperfusion determines the treatment effect of endovascular thrombectomy. We evaluated stent-retriever characteristics and their relation to reperfusion in the ESCAPE-NA1 trial.Independent re-scoring of reperfusion grade for each attempt was conducted. The following characteristics were evaluated: stent-retriever length and diameter, thrombus position within stent-retriever, bypass effect, deployment in the superior or inferior MCA trunk, use of balloon guide catheter and distal access catheter. Primary outcome was successful reperfusion defined as expanded thrombolysis in cerebral infarction (eTICI) 2b-3 per attempt. The secondary outcome was successful reperfusion eTICI 2b-3 after the first attempt. Separate regression models for each stent-retriever characteristic and an exploratory multivariable modeling to test the impact of all characteristics on successful reperfusion were built.Of 1105 patients in the trial, 809 with the stent-retriever use (1241 attempts) were included in the primary analysis. The stent-retriever was used as the first-line approach in 751 attempts. A successful attempt was associated with thrombus position within the proximal or middle third of the stent (OR 2.06; 95% CI: 1.24-3.40 and OR 1.92; 95% CI: 1.16-3.15 compared to the distal third respectively) and with bypass effect (OR 1.7; 95% CI: 1.07-2.72). Thrombus position within the proximal or middle third (OR 2.80; 95% CI: 1.47-5.35 and OR 2.05; 95% CI: 1.09-3.84, respectively) was associated with first-pass eTICI 2b-3 reperfusion. In the exploratory analysis accounting for all characteristics, bypass effect was the only independent predictor of eTICI 2b-3 reperfusion (OR 1.95; 95% CI: 1.10-3.46).The presence of bypass effect and thrombus positioning within the proximal and middle third of the stent-retriever were strongly associated with successful reperfusion.

Infarct lesion volume (ILV) may serve as an imaging biomarker for clinical outcomes in the early post-treatment stage in patients with acute ischemic stroke. The aim of this study was to evaluate the inter- and intra-rater reliability of manual segmentation of ILV on follow-up non-contrast CT (NCCT) scans. Fifty patients from the Prove-IT study were randomly selected for this analysis. Three raters manually segmented ILV on 24-h NCCT scans, slice by slice, three times. The reference standard for ILV was generated by the Simultaneous Truth And Performance Level estimation (STAPLE) algorithm. Intra- and inter-rater reliability was evaluated, using metrics of intraclass correlation coefficient (ICC) regarding lesion volume and the Dice similarity coefficient (DSC). Median age of the 50 subjects included was 74.5 years (interquartile range [IQR] 67–80), 54% were women, median baseline National Institutes of Health Stroke Scale was 18 (IQR 11–22), median baseline ASPECTS was 9 (IQR 6–10). The mean reference standard ILV was 92.5 ml (standard deviation (SD) ± 100.9 ml). The manually segmented ILV ranged from 88.2 ± 91.5 to 135.5 ± 119.9 ml (means referring to the variation between readers, SD within readers). Inter-rater ICC was 0.83 (95%CI: 0.76–0.88); intra-rater ICC ranged from 0.85 (95%CI: 0.72–0.92) to 0.95 (95%CI: 0.91–0.97). The mean DSC among the three readers ranged from 65.5 ± 22.9 to 76.4 ± 17.1% and the mean overall DSC was 72.8 ± 23.0%. Manual ILV measurements on follow-up CT scans are reliable to measure the radiological outcome despite some variability.

Background: Intravenous thrombolysis improves functional outcome in patients with acute stroke and frequencies of r-tPA (recombinant tissue-type plasminogen activator) treatment have been increasing over time. We aimed to assess whether functional outcome in r-tPA–treated patients improved over time and to investigate the influence of clinical variables on functional outcome. Methods: We analyzed data of r-tPA–treated patients in the Austrian Stroke Unit Registry from 2006 to 2019. Favorable functional outcome was defined as modified Rankin Scale score of 0 to 2. Frequencies of modified Rankin Scale score of 0 to 2 were assessed for the overall population and in prespecified subgroups; multivariable logistic regression analysis was performed to assess associations of baseline characteristics including clinically relevant interactions, and outcome. Results: Overall, 4865 out of 9409 r-tPA–treated patients (51.7%) achieved favorable functional outcome 3 months post stroke. Between 2006 and 2019, frequencies of favorable functional outcome increased from 45.9% to 56.8%. In multivariable logistic regression analysis, year of treatment (adjusted odds ratio [adjOR], 1.08 [95% CI, 1.01–1.15]) was associated with favorable functional outcome. Stroke severity (National Institutes of Health Stroke Scale, adjOR, 0.86 [95% CI, 0.85–0.87]), age (61–70 years: adjOR, 0.67 [95% CI, 0.55–0.80], 71–80 years: adjOR, 0.42 [95% CI, 0.35–0.50], >80 years: adjOR, 0.16 [95% CI, 0.13–0.20]), female sex (adjOR, 0.89 [95% CI, 0.79–0.99]), and various comorbidities (eg, atrial fibrillation, prior stroke, diabetes) were negatively associated. Inclusion of interaction terms into the multivariable logistic regression model suggests a positive effect of year of treatment and endovascular treatment by increasing stroke severity on functional outcome (interaction between year of treatment and National Institutes of Health Stroke Scale: adjOR, 1.01 [95% CI, 1.00–1.02], interaction between National Institutes of Health Stroke Scale and endovascular treatment: adjOR, 1.02 [95% CI, 1.01–1.03]). Conclusions: Frequencies of favorable functional outcome in r-tPA–treated patients have been increasing over time, likely driven by improved outcome in patients with more severe strokes receiving endovascular treatment. However, some subgroups are still less likely to achieve functional independency and deserve particular attention.

Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To investigate the association of qualitative and quantitative infarct variables at 24-hour follow-up noncontrast CT and diffusion-weighted MRI with 90-day clinical outcome. Materials and Methods The Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke, or ESCAPE-NA1, randomized controlled trial enrolled patients with large-vessel-occlusion stroke undergoing mechanical thrombectomy from March 1, 2017, to August 12, 2019. In this post hoc analysis of the trial, qualitative infarct variables (predominantly gray [vs gray and white] matter involvement, corticospinal tract involvement, infarct structure [scattered vs territorial]) and total infarct volume were assessed at 24-hour follow-up noncontrast CT or diffusion-weighted MRI. White and gray matter infarct volumes were assessed in patients by using follow-up diffusion-weighted MRI. Infarct variables were compared between patients with and those without good outcome, defined as a modified Rankin Scale score of 0-2 at 90 days. The association of infarct variables with good outcome was determined with use of multivariable logistic regression. Separate regression models were used to report effect size estimates with adjustment for total infarct volume. Results Qualitative infarct variables were assessed in 1026 patients (mean age ± standard deviation, 69 years ± 13; 522 men) and quantitative infarct variables were assessed in a subgroup of 358 of 1026 patients (mean age, 67 years ± 13; 190 women). Patients with gray and white matter involvement (odds ratio [OR] after multivariable adjustment, 0.19; 95% CI: 0.14, 0.25; P < .001), corticospinal tract involvement (OR after multivariable adjustment, 0.06; 95% CI: 0.04, 0.10; P < .001), and territorial infarcts (OR after multivariable adjustment, 0.22; 95% CI: 0.14, 0.32; P < .001) were less likely to achieve good outcome, independent of total infarct volume. Conclusion Infarct confinement to the gray matter, corticospinal tract sparing, and scattered infarct structure at 24-hour noncontrast CT and diffusion-weighted MRI were highly predictive of good 90-day clinical outcome, independent of total infarct volume. Clinical trial registration no. NCT02930018 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mossa-Basha in this issue.

Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual.Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Background and Purpose: The prognosis of medium vessel occlusions (MeVOs), that is, M2/3 middle cerebral artery, A2/3 anterior cerebral artery, and P2/3 posterior cerebral artery occlusions, is generally better compared with large vessel occlusions, since brain ischemia is less extensive. However, in some MeVO patients, infarcts are seen outside the territory of the occluded vessel (MeVO with discrepant infarcts). This study aims to determine the prevalence and clinical impact of discrepant infarct patterns in acute ischemic stroke due to MeVO. Methods: We pooled data of MeVO patients from INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRove-IT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy)—2 prospective cohort studies of patients with acute ischemic stroke. The combination of occlusion location on baseline computed tomography angiography and infarct location on follow-up computed tomography/magnetic resonance imaging was used to identify MeVOs with discrepant infarct patterns. Two definitions for discrepant infarcts were applied; one was more restrictive and purely based on infarct patterns of the basal ganglia, whereas the second one took cortical infarct patterns into account. Clinical outcomes of patients with versus without discrepant infarcts were summarized using descriptive statistics. Logistic regression was performed to obtain adjusted effect size estimates for the association of discrepant infarcts and good outcome, defined as a modified Rankin Scale score of 0 to 2, and excellent outcome (modified Rankin Scale score 0–1). Results: Two hundred sixty-two patients with MeVO were included in the analysis. The prevalence of discrepant infarcts was 39.7% (definition 1) and 21.0% (definition 2). Patients with discrepant infarcts were less likely to achieve good outcome (definition 1: adjusted odds ratio, 0.48 [95% CI, 0.25–0.91]; definition 2: adjusted odds ratio, 0.47 [95% CI, 0.22–0.99]). When definition 1 was applied, patients with discrepant infarcts were also less likely to achieve excellent outcome (definition 1: adjusted odds ratio, 0.55 [95% CI, 0.31–0.99]; definition 2: adjusted odds ratio, 0.62 [95% CI, 0.31–1.25]). Conclusions: MeVO patients with discrepant infarcts are common, and they are associated with more severe deficits and poor outcomes.

BackgroundThe optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial.MethodsESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling.ResultsAmong 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0–2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0–2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1).ConclusionsTandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).

Background: Time from imaging to establishing reperfusion is a major influencer of clinical outcomes and over the years thrombectomy techniques have evolved rapidly. This has led to improvements in achieving fast and complete reperfusion. We analyzed the impact of various intra-procedural techniques and tools on the speed of reperfusion and correlated procedural duration with probability of achieving good clinical outcomes. Methods: We analyzed intra-procedural time metrics and examined factors leading to delays during EVT. The relationship between outcome (mRS Scale) and procedural time from arterial puncture to time of achieving mTICI 2b-3 First Reperfusion (FRE) was modeled using logistic regression. Results: The various procedural time metrics are summarized in Figure 1. Every 10-minute increase in FRE time reduced the probability of achieving functional independence(90-day modified Rankin Scale 0-2) by 6.7% (P=0.021, adjusted). The medianFRE timewas 25min (IQR 17-39) and was significantly longer in patients with tandem occlusions(median 34min, p 0.0005). General anesthesia vs procedural sedation vs no sedation use did not significantly alter the FRE time (p = 0.1453). The use of BGC (54.2%) was nominally longer FRE (median 26min “IQR 18-38” vs 23ming, “IQR 16-38”; p 0.095)while the use of contact aspiration (n=213) vs retrievable stents (n=676) as the first approach was associated with a shorter FRE time (21min “IQR 14-35” vs 26 min “IQR18-40”, p =0.001). Conclusions: Puncture to first reperfusion time is a significant predictor of clinical outcome in theESCAPE-NA1 trial. Various procedural and anatomical factors influence this timemetric. Figure: Intra-Procedural workflow time metrics expressed in medians and 90th percentiles. The cumulative times are calculated for each major milestone in the procedure for upto three attempts. First reperfusion duration where TICI 2b was achieved is shown in comparison to other procedural time metrics.

Purpose: We assessed whether balloon guide catheter (BGC) use during endovascular thrombectomy (EVT) influences procedural and clinical outcomes in the ESCAPE-NA1 trial. Methods: ESCAPE-NA1 was an international multicenter trial that randomized large vessel occlusion stroke patients who underwent endovascular thrombectomy (EVT) to receive Nerinetide vs. placebo. Information on EVT techniques and devices was extracted from angiographic images and procedure report forms. Effect estimates of BGC use on angiographic and clinical outcomes were obtained with logistic regression with adjustment for age, ASPECTS, baseline NIHSS, occlusion site, alteplase and study drug treatment. Results: Detailed information on EVT devices and technique was available for 891/1105 (80.6%) patients. A BGC was used in 599/891 patients (67.2%). BGC use was most common with a retrievable stent use (with or without distal access catheter) as the first-line approach (in 252/266 cases [94.7%] vs. combined approach (both aspiration and SR): 288/414 [69.6%], vs. contact aspiration: 37/159 cases [23.3%]). Overall, eTICI 2b/3 rates with vs. without BGC did not differ significantly (525/598 [87.8%] vs. 260/292 [89.0%]), but eTICI 2c/3 rates were significantly higher when a BGC was used (304/598 [50.8%] vs. 126/292 [43.2%], adjusted OR 1.39 [95%CI 1.05 - 1.9]). Good outcomes (mRS 0-2) were not associated with BGC use (adjusted OR 1.07 [95%CI 0.78 - 1.48]). Conclusion: BGC use was associated with a greater proportion of near-complete reperfusion, while there was no significant association with clinical outcomes.

Background: The degree of cortical venous opacification could reflect the degree of ischemia in tandem occlusions strokes. We assessed the association between asymmetric cortical vein opacification and outcome among patients with acute ischemic stroke and tandem occlusion. Methods: ESCAPE NA1 was a multicenter randomized-controlled trial comparing medical treatments nerinetide vs. placebo in patients with acute ischemic stroke and large vessel occlusion who underwent EVT. Tandem carotid occlusion was defined as complete occlusion of the ICA on catheter angiography. We assessed cortical venous opacification on baseline CTA using the COVES score (Jansen, et al. Radiology 2019, ranging from 0-6 with lower numbers indicating poor cortical venous filling, and dichotomized to 0 vs. 1-6). The influence of cortical venous opacification on functional outcome was analyzed using regression modelling with adjustment for age, baseline NIHSS and ASPECTS, thrombolysis and treatment allocation. Results: We assessed 115 patients with tandem occlusion. Median COVES score was 2 (IQR 1-3) with 9 patients (8%) scoring 0 (complete absence of cortical venous filling). Patients with COVES 0 were less likely to have good leptomeningeal collaterals (good collaterals: COVES 0: 0/9 (0%) vs. COVES 1-6: 19/102 (18%), p = 0.007). Patients with COVES 0 were less likely to achieve good outcome (mRS 0-2, COVES 0: 3/9 patients (33%) vs. COVES 1-6: 79/106 (74%), p=0.016). Cortical venous filling was significantly associated with good functional outcome on univariable analysis (OR 5.9, 95%CI 1.4 - 25.0), and after adjustment for baseline variables (OR 8.6, 95%CI 1.4 - 51.0). Cervical carotid angioplasty and/or stenting did not modify functional outcome after adjustment for COVES score. Conclusion: Impaired venous drainage is a marker of poor pial collaterals and is associated with poorer outcome in tandem occlusion patients.

Background: We evaluated technical aspects of stent retriever use and its relation to reperfusion in ESCAPE NA1 trial. Methods: ESCAPE-NA1 was a multicenter, international randomized trial assessing the efficacy of nerinetide in ischemic stroke patients who underwent EVT within 12h from onset. The following stent retriever characteristics were evaluated: stent retriever length, diameter, thrombus position in relation to stent retriever - proximal, middle or distal third, bypass effect during stent retriever deployment (Figure 1), and stent retriever placement in the anterior or posterior MCA trunk (in M1 occlusions). Primary outcome was reperfusion grade and the unit of analysis was stent retriever attempt. Results: Data from 1062 patients were evaluated. Angiographic data for up to three passes were analyzed as only 8.9% of patients required >3 passes. Stent retriever was used in 1241 passes in 808 patients. The occlusion sites were terminal ICA (14.9%), M1 MCA (58.7%), M2 MCA (23.7%), other (2.1%). A successful reperfusion attempt (mTICI 2b-3) was associated with the presence of bypass effect (OR 1.7; 95%CI 1.07-2.72), and positioning of stent retriever so the thrombus was in the proximal and middle third of stent retriever (OR 2.06; 95%CI 1.24-3.40 and OR 1.92; 95%CI 1.16-3.15, respectively). The position of the thrombus in the middle third of stent retriever was a significant predictor of bypass effect (OR 2.71; 95%CI 1.61-4.58). Stent retriever length, diameter, or choice of MCA trunk did not predict successful attempts, Table 1. Conclusion: Bypass effect and positioning of stent retriever so the thrombus was in proximal 2/3rds are predictors of successful reperfusion attempts.

Introduction: Infarct in new territory (INT) is a known complication of endovascular therapy. We assessed the prevalence, predictors and clinical relevance of INT Methods: We included patients from the ESCAPE-NA1: a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in patients with acute ischemic stroke who underwent EVT within 12 hours from onset. All imaging was re-evaluated, and INT was defined by presence of infarct in new vascular territory, outside the baseline target occlusion(s) on follow up CT and MRI. INT’s were classified by maximum diameter (20mm) and location. Results: Of 1099 analyzed patients in ESCAPE NA1, 107 had INT (9.7%, mean age 67 years, 51.4% females). There were no differences at baseline in those with vs without INT. Most INTs (75.7%) were angiographically occult and 41(38.3%) were > 20mm. The most common INT territory was the ACA alone or in combination with MCA/PCA (30.3%). The presence of emboli in new territory angiographically was significantly associated with INT (OR 16.39, 95%CI 8.14-33.09). Alteplase use, balloon guide catheter use, nerinetide and initial occlusion site did not predict INT. INT patients had higher final median infarct volumes compared to non-INT (44.5cc vs 23.3cc, P20mm) were associated with poor clinical outcome compared to INT ( Conclusion: Infarcts in new territory are common and are associated with poor outcome.

Objective: To determine the prevalence of non-stenotic carotid plaques ( Methods: Data was analyzed from the STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)—a prospective, nonrandomized study of patients undergoing thrombectomy with the Solitaire device. Prevalence of non-stenotic carotid plaques, ipsilateral and contralateral to the stroke was compared in patients with ESUS and cardioembolic strokes. Plaque features were further compared within both subgroups between patients with and without ipsilateral stroke. Uni- and multivariable logistic regression was performed to determine associations between non-stenotic carotid plaque, plaque characteristics, and ipsilateral stroke in both subgroups. Results: Of the 946 patients in the database, 226 patients with cardioembolic stroke (median age, 72 years) and 141 patients with ESUS (median age, 69 years) were included in the analysis.The prevalence of non-stenotic carotid plaque in the cardioembolic and ESUS subgroups was 33/226 (14.6%) and 32/141(22.7%) respectively. Bilateral non-stenotic carotid plaques were seen in 10/226(4.4%) cardioembolic and 13/141(9.2%) ESUS patients. Non-stenotic carotid plaques were significantly associated with ipsilateral strokes in cardioembolic stroke (aOR,1.91 [95% CI,1.15-3.18]) and in ESUS (aOR,1.69 [95% CI, 1.05-2.73]). Plaque irregularity, plaque hypodensity and increasing plaque thickness were significantly associated with ipsilateral stroke, only in the ESUS subgroup. Conclusion: Non-stenotic carotid plaques were significantly associated with ipsilateral stroke in cardioembolic and ESUS subgroups and there was increased association of hypodense plaque, increasing plaque thickness and plaque irregularity with ipsilateral stroke in the ESUS subgroup, suggesting these plaques could be a potential cause of stroke in these patient subgroups.

Purpose: In this post-hoc analysis of the ESCAPE-NA1 trial, we investigated the prevalence of deep grey matter infarcts and their influence on clinical outcome. Methods: Infarcts on 24 hour follow up imaging (non contrast head CT or diffusion-weighted MRI) were categorized as predominantly deep grey matter infarcts (caudate and/or lentiform nucleus infarcts with sparing of the superficial grey matter and white matter) vs. other infarcts. Total infarct volume was manually segmented in all patients. When MRI follow-up was available, deep grey matter and grey matter infarct volumes were segmented separately. Multivariable logistic regression with adjustment for key minimization variables and by infarct volume was used to assess the association of predominantly deep grey matter infarcts and good outcome. Results: Of the 1026 included patients, 316 (30.8%) had predominantly deep grey matter infarcts. Cumulative proportions of good outcome for overall, grey matter, deep grey matter, and superficial grey matter infarct volumes are shown in the figure. Good outcomes were more frequently achieved in patients with predominantly deep grey matter infarcts (239/316 [75.6%] vs. 374/704 [53.1%]). Deep infarcts were tightly correlated with infarct volume (Pearson rho -0.35) and in multivariable analysis deep grey matter infarcts were predictive of outcome overall; when examined in volume percentiles, there was no effect of deep infarct location. Conclusion: Predominantly deep grey matter infarcts are associated with good outcomes. Deep grey matter infarct location favorable prognosis is associated with small overall infarct size.

Purpose: We investigated the prevalence and prognostic impact on outcome of any intracranial hemorrhage, hemorrhage morphology, type and volume in acute ischemic stroke patients undergoing mechanical thrombectomy. Methods: Prevalence of intracranial hemorrhage, hemorrhage type, morphology and volume was determined on 24h follow-up imaging (non contrast head CT or gradient-echo/susceptibility-weighted MRI). Proportions of good outcome (mRS 0-2 at 90 days) were reported for patients with vs. without any intracranial hemorrhage. Multivariable logistic regression with adjustment for key minimization variables and total infarct volume was performed to obtain adjusted effect size estimates for hemorrhage type and volume on good outcome. Results: Hemorrhage on follow up-imaging was seen in 372/1097 (33.9%) patients, among them 126 (33.9%) with hemorrhagic infarction (HI) type 1, 108 (29.0%) with HI-2, 72 /19.4%) with parenchymal hematoma (PH) type 1, 37 (10.0) with PH2, 8 (2.2%) with remote PH and 21 (5.7%) with extra-parenchymal/intraventricular hemorrhage. Good outcomes were less often achieved by patients with hemorrhage on follow-up imaging (164/369 [44.4%] vs. 500/720 [69.4%]). Any type of intracranial hemorrhage was strongly associated with decreased chances of good outcome ( adj OR 0.62 [CI 95 0.44 - 0.87]). The effect of hemorrhage was driven by both PH hemorrhage sub-type [PH-1 ( adj OR 0.39 [CI 95 0.21 - 0.72]), PH-2 ( adj OR 0.15 [CI 95 0.05 - 0.50])] and extra-parenchymal/intraventricular hemorrhage ( adj OR 0.60 (0.20-1.78) Petechial hemorrhages (HI-1 and HI-2) were not associated with poorer outcomes. Hemorrhage volume ( adj OR 0.97 [CI 95 0.05 - 0.99] per ml increase) was significantly associated with decreased chances of good outcome. Conclusion: Presence of any hemorrhage on follow-up imaging was seen in one third of patients and strongly associated with decreased chances of good outcome.

Introduction: Emboli in new territory (ENT) are known potential complication of endovascular thrombectomy. We explored their incidence and predictors in ESCAPE-NA-1 trial. Methods: We included patients from the ESCAPE-NA1: a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in patients with acute ischemic stroke who underwent EVT within 12 hours from onset. All the imaging was reassessed, and ENT was defined as angiographic evidence of emboli in vascular territories other than the MCA, which was not present in the initial CT angiogram. We collected details of management and its influence on outcomes. Results: We analyzed 1095 patients from the ESCAPE NA1. ENT occurred in 40 patients (3.6%, mean age 69.5 years, 50% females). There were no significant differences at baseline in groups with and without ENT. Most common ENT site was ACA (38,95%). Thrombolysis, use of balloon guide catheter, nerinetide treatment, and initial occlusion site did not predict ENT. Seven ENTs (17.5%) were pursued with endovascular therapy: retrievable stents in 6 patients and intra-arterial thrombolysis in 1 patient. Patients with ENT had longer total arterial puncture to first reperfusion times (65 vs 40.5 minutes, P Conclusion: The incidence of ENT was low in ESCAPE NA1 trial but associated with poorer clinical outcomes.

Background: We evaluated clinical outcome in relation to the degree of reperfusion in ESCAPE-NA1 trial. Methods: ESCAPE-NA1 was a multicenter, international randomized trial assessing the efficacy of nerinetide in ischemic stroke patients who underwent EVT within 12h from onset. Independent clinical outcome [90-days modified Rankin Scale (mRS) 0-2], excellent clinical outcome (90-days mRS 0-1), isolated subarachnoid hemorrhage with no parenchymal hemorrhage (iSAH) or symptomatic hemorrhage (sICH) on follow-up imaging, and death were compared between a treatment group and control group with respect to the level of reperfusion defined as mTICI. Univariable and multivariable logistic regression analyses were performed. Results: Data from 1090 patients were assessed. The occlusion locations were terminal ICA (18.3%), M1 MCA (61.8%,) M2 MCA (15.1%), other - e.g. M3 (3.7%). Final mTICI 0-1 was achieved in 5.5% of patients, mTICI 2a in 7.5%, mTICI 2b in 40.8%, mTICI 2c in 26.6% and mTICI 3 in 19.5%. Isolated SAH was present in 1.7% and sICH in 3%. There was no significant difference between the nerinetide and control groups in the reperfusion grade, presence of iSAH or sICH, or in clinical outcome. Odds of independent outcomes (mRS 0-2) and odds of excellent outcome (mRS 0-1) were significantly increasing with each improved reperfusion grade, Table 1. Sixty percent of patients with final mTICI 2b, 70% with mTICI 2c and 69% with mTICI 3 achieved good clinical outcome in comparison to 30% of patients with mTICI 0-2a. The incidence of iSAH was significantly lower in the NA1 arm (OR 0.28, 95%CI: 0.09-0.86, p=.027) adjusting for reperfusion status. Conclusion: Degrees of better reperfusion are strongly associated with better outcomes and reduced mortality. mTICI 2c-3 reperfusion should be a standard goal of EVT.

Background: The optimal treatment for stroke patients with tandem cervical carotid occlusion is debated. We analyzed the treatment strategies and outcomes of tandem occlusion patients in the ESCAPE NA1 trial. Methods: ESCAPE NA1 was a multicenter international randomized trial of nerinetide vs. placebo in patients with acute ischemic stroke who underwent EVT. We defined tandem occlusions as complete occlusion of the cervical ICA on catheter angiography. The influence of tandem occlusions on outcome was analyzed using regression modeling with adjustment for age, sex, baseline NIHSS and ASPECTS, occlusion location, thrombolysis and treatment allocation. Results: 115 of 1105 patients (10.4%) had tandem occlusions. 73/115 tandem patients (66.0%) received treatment for the cervical occlusion: 21.9% were stented before thrombectomy, 68.5% were stented after thrombectomy, and 8.2% had angioplasty alone. Successful reperfusion was significantly higher in patients who had thrombectomy first followed by carotid treatment (eTICI 2b-3: 40/40 (100.0%)) or carotid angioplasty before and cervical stent after intracranial thrombectomy (9/10 (90.0%)) compared to carotid intervention before intracranial thrombectomy: (19/23 (82.1%), p=0.016). 90-day mRS 0-2 was achieved in 82/115 patients (71.3%) with tandem occlusions (treated occlusions: 74.0%, untreated: 66.7%) compared to 579/981 (59.5%) patients without tandem occlusions. In adjusted analysis, tandem occlusion was not predictive of outcome. In the subgroup of tandem patients, cervical stent-treatment was nominally associated with better outcomes (OR 2.2, 95% CI 0.5 - 9.2). Conclusion: Cervical carotid stenting may improve outcomes for EVT patients with tandem occlusions, but these results are limited by the sample size and non-randomized selection of patients for stenting.

Glioblastoma might have widespread effects on the neural organization and cognitive function, and even focal lesions may be associated with distributed functional alterations. However, functional changes do not necessarily follow obvious anatomical patterns and the current understanding of this interrelation is limited. In this study, we used resting-state functional magnetic resonance imaging to evaluate changes in global functional connectivity patterns in 15 patients with glioblastoma. For six patients we followed longitudinal trajectories of their functional connectome and structural tumour evolution using bi-monthly follow-up scans throughout treatment and disease progression. In all patients, unilateral tumour lesions were associated with inter-hemispherically symmetric network alterations, and functional proximity of tumour location was stronger linked to distributed network deterioration than anatomical distance. In the longitudinal subcohort of six patients, we observed patterns of network alterations with initial transient deterioration followed by recovery at first follow-up, and local network deterioration to precede structural tumour recurrence by two months. In summary, the impact of focal glioblastoma lesions on the functional connectome is global and linked to functional proximity rather than anatomical distance to tumour regions. Our findings further suggest a relevance for functional network trajectories as a possible means supporting early detection of tumour recurrence.

BACKGROUND: Severe carotid stenosis carries a high risk of stroke. However, the risk of stroke with nonstenotic carotid plaques (10 patients with 50% were extracted if reported. DATA SYNTHESIS: We identified 31 studies reporting on the risk of ipsilateral stroke/TIA in patients with nonstenotic carotid plaques. Twenty-five studies (n = 13,428 participants) reported on first-ever stroke/TIA and 6 studies (n = 122 participants) reported on the recurrence of stroke/TIA. DATA ANALYSIS: The incidence of first-ever ipsilateral stroke/TIA was 0.5/100 person-years. The risk of recurrent stroke/TIA was 2.6/100 person-years and increased to 4.9/100 person-years if intraplaque hemorrhage was present. The risk of progression to severe stenosis (>50%) was 2.9/100 person-years (8 studies, n = 448 participants). LIMITATIONS: Included studies showed heterogeneity in reporting stroke etiology, the extent of stroke work-up, imaging modalities, and classification systems used for characterizing carotid stenosis. CONCLUSIONS: The risk of recurrent stroke/TIA in nonstenotic carotid plaques is not negligible, especially in the presence of high-risk plaque features. Further research is needed to better define the significance of nonstenotic carotid plaques for stroke etiology.

Non-stenotic (50%) carotid plaques have recently been recognized as a potential source of stroke. This meta-analysis aims to summarize the prevalence of non-stenotic carotid plaques in stroke patients in general and in patients with embolic stroke of undetermined source in particular.We performed a comprehensive systematic review of the literature and meta-analysis on acute ischemic stroke patients in whom carotid imaging was performed using the MEDLINE, Embase and Cochrane database, including studies published up to December 2019. Keywords were "stroke", "transient ischemic attack", "carotid", "plaque", "atherosclerosis" and "disease". Included studies had ≥10 patients with acute ischemic stroke and reported the prevalence of non-stenotic (50%%stenosis) carotid plaques detected on any imaging modality.We included forty-five studies (n = 18304 patients, 48.4% males, mean age 63.6 years) in our meta-analysis. Imaging modalities used were ultrasound (n = 26 studies), CT-angiography (n = 7), magnetic resonance-imaging (n = 8) and catheter angiography (n = 4). The overall prevalence of non-stenotic carotid plaques was 51% (95% CI: 43 - 59). 10 studies included mainly patients with embolic stroke of undetermined source (50% of all patients). The pooled prevalence of non-stenotic carotid plaques in these studies was 55% (95% CI: 42 - 68). 23 studies explicitly reported ipsilateral non-stenotic carotid plaques, the pooled prevalence of which was 51% (95% CI: 45 - 59).In this meta-analysis, non-stenotic carotid plaques were present in more than 50% of all acute ischemic stroke patients, with a slightly higher prevalence in ESUS patients. Given the potential role of non-stenotic carotid plaques in stroke etiology, particularly in ESUS, further research should aim to identify criteria that predict the stroke risk associated with non-stenotic carotid plaques.

Background and Purpose— Embolic stroke of undetermined source (ESUS) constitutes a large proportion of acute ischemic stroke. It is crucial to identify possible stroke etiologies in this patient subgroup to individually tailor secondary stroke prevention strategies. This study aimed to assess the prevalence of carotid plaques causing Methods— Patients from INTERRSeCT—a multicenter prospective study of patients with acute ischemic stroke—were included in this study if their stroke etiology was not large artery atherosclerosis (>50% stenosis), and neck computed tomography angiography was obtained. Degree of stenosis ( Results— Four hundred forty-six patients were included in the study (median age, 73 years; 218 men), 138 of which were ESUS patients (median age, 70 years; 61 men). Nonstenotic carotid plaques (with P =0.004). Nonstenotic carotid plaques were significantly associated with ipsilateral strokes (adjusted odds ratio, 1.83 [95% CI, 1.05–3.18]). Conclusions— In patients with ESUS, nonstenotic carotid plaques were significantly more common on the side of the ischemic stroke, suggesting that these plaques could be a potential stroke etiology in patients in whom the ischemic stroke is classified currently as ESUS.

Background and Purpose— Frequencies of treatment with r-tPA (recombinant tissue-type plasminogen activator) are increasing over the past 15 years. However, published data on the influence of various demographic and clinical factors on r-tPA treatment as well as estimates of future trajectories are limited. We evaluated time trends and future trajectories of r-tPA treatment in patients with acute stroke and the influence of various factors on r-tPA treatment by analyzing data of 103 970 patients enrolled in the Austrian Stroke Unit Registry from 2006 to 2018, of which 18 953 were treated with r-tPA. Methods— Time trends of r-tPA-treatment were investigated in predefined subgroups (minor/major stroke, age, anterior/posterior circulation stroke); limited exponential time series models were calculated to estimate future trends of r-tPA-treatment. Logistic regression models were calculated to estimate the influence of clinical variables on r-tPA-treatment. Results— Overall, r-tPA treatment frequencies increased from 9.9% in 2006 to 21.8% in 2018. We observed a particular increase in patients >80 years, patients presenting with a National Institutes of Health Stroke Scale Score of 2 to 3, patients with posterior circulation stroke, patients with wake-up stroke, and patients without atrial fibrillation. Forecast of overall r-tPA frequencies predicted a further but flattened increase up to 24% by 2025. Logistic regression of time-dependent associations of clinical variables with r-tPA-treatment revealed increasing odds of r-tPA-treatment in patients with a posterior circulation stroke and decreasing odds of r-tPA-treatment in patients with atrial fibrillation. Conclusions— We observed a positive development of r-tPA-treatment frequencies mirroring increasing confidence with intravenous thrombolysis in clinical practice; however, decreasing odds of r-tPA-treatment over time in patients with atrial fibrillation deserve particular attention.

Background and Purpose— Posterior circulation stroke (PCS) account for 20% of all ischemic strokes. There is limited evidence whether functional outcome of PCS is comparable to that of anterior circulation stroke (ACS). We aimed to analyze whether 3-month functional outcome is different in PCS and ACS. Methods— Patients with acute ischemic stroke prospectively enrolled within the Austrian Stroke Unit Registry were stratified by infarct localization according to the Oxfordshire Community Stroke Project Classification. Propensity score matching was used to control for covariate imbalances and to match patients with PCS and ACS. Patients were matched for stroke severity, recombinant tissue-type plasminogen activator treatment, and demographic and vascular risk factors. Main outcomes were the distribution of modified Rankin Scale after 3 months and multiple proportional odds models to estimate the influence of the infarct localization on the functional outcome. Results— From a total of 90 484 patients enrolled within the Austrian Stroke Unit Registry, 9208 (4604 PCS/4604 ACS) were matched, of those 954 (477 in each group) were treated with recombinant tissue-type plasminogen activator. We detected a significant shift towards better 3-month functional outcome in patients with ACS compared with PCS (odds ratio [OR], 1.19; 95% CI, 1.1–1.28; P 270 minutes (OR, 1.34; 95% CI, 1.17–1.54; P P P =0.3554; 181–270 minutes: OR, 1.04, 95% CI, 0.79–1.37, P =0.7689). In patients treated with recombinant tissue-type plasminogen activator, functional outcome was not significantly different between PCS and ACS. Conclusions— PCS was associated with worse outcome compared with ACS in patients arriving later than 4.5 hours at hospital or in those with unknown onset of symptoms. Our results urge for implementation of symptoms found in the posterior circulation into preclinical patient-triage tools.

CDKN2A is the most prominent familial melanoma gene, with mutations occurring in up to 40% of the families. Numerous mutations in the gene are known, several of them representing regional founder mutations. We sought to determine, for the first time, germline mutations in CDKN2A in Austria to identify novel mutations. In total, 700 individuals (136 patients with a positive family history and 164 with at least two primary melanomas as the high-risk groups; 200 with single primary melanomas; and 200 healthy individuals as the control groups) were Sanger sequenced for CDKN2A exon 1α, 1β, and 2. The 136 patients with affected relatives were also sequenced for CDK4 exon 2. We found the disease-associated mutations p.R24P (8×), p.N71T (1×), p.G101W (1×), and p.V126D (1×) in the group with affected relatives and p.R24P (2×) in the group with several primary melanomas. Furthermore, we discovered four mutations of unknown significance, two of which were novel: p.A34V and c.151-4 GC, respectively. Computational effect prediction suggested p.A34V as conferring a high risk for melanoma, whereas c.151-4 GC, although being predicted as a splice site mutation by MutationTaster, could not functionally be confirmed to alter splicing. Moreover, computational effect prediction confirmed accumulation of high-penetrance mutations in high-risk groups, whereas mutations of unknown significance were distributed across all groups. p.R24P is the most common high-risk mutation in Austria. In addition, we discovered two new mutations in Austrian melanoma patients, p.A34V and c.151-4 GC, respectively.

Systems consisting of a bilindione or dipyrrinone chromophore and a covalently attached, but nonconjugated, fluorescing naphthyl, anthranyl, and indolyl residue were prepared and their luminescence properties measured. Excitation energy is very effectively quenched by the dipyrrin radiationless deexcitation channel of bilins as well as by the photodiastereomerization mode of dipyrrinone fragments. A Forster type energy transfer mechanism is inferred from intermolecular Stern-Volmer kinetics in solvents of different viscosity.

A violinoid and a 2,3-dihydrobilindione chromophore is attachedvia an appendix anchored at rings A of the pigments by means of reacting them with the polyacryl-N-acryloxysuccinimid copolymer to yield water-soluble chromopolymers. They are characterized by a molecular mass of about 4000 to 6000 and a relation of one chromophoric unit per 6 to 22 monomers. Their absorption spectra and circular dichroism recorded in water and dimethylsulfoxide as solvents are discussed with respect to structural aspects, and in comparison with monomeric chromophore derivatives.