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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.

Background Intracranial hemorrhage is a known complication after endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion, but the association between radiologic hemorrhage severity and outcome is controversial. Purpose To investigate the prevalence and impact on outcome of intracranial hemorrhage and hemorrhage severity after endovascular stroke treatment. Materials and Methods The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial enrolled participants with acute large vessel occlusion stroke who underwent endovascular treatment from March 1, 2017, to August 12, 2019. Evidence of any intracranial hemorrhage, hemorrhage multiplicity, and radiologic severity, according to the Heidelberg classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], and parenchymal hematoma type 2 [PH2]) was assessed at CT or MRI 24 hours after endovascular treatment. Good functional outcome, defined as a modified Rankin score of 0-2 at 90 days, was compared between participants with intracranial hemorrhage and those without intracranial hemorrhage at follow-up imaging and between hemorrhage subtypes. Poisson regression was performed to obtain adjusted effect size estimates for the presence of any intracranial hemorrhage and hemorrhage subtypes at good functional outcome. Results Of 1097 evaluated participants (mean age, 69 years ± 14 [standard deviation]; 551 men), any degree of intracranial hemorrhage was observed in 372 (34%). Good outcomes were less often achieved among participants with hemorrhage than among those without hemorrhage at follow-up imaging (164 of 372 participants [44%] vs 500 of 720 [69%], respectively; P < .01). After adjusting for baseline variables and infarct volume, intracranial hemorrhage was not associated with decreased chances of good outcome (adjusted risk ratio [RR] = 0.91 [95% CI: 0.82, 1.02], P = .10), but there was a graded relationship of radiologic hemorrhage severity and outcomes, whereby PH1 (RR = 0.77 [95% CI: 0.61, 0.97], P = .03) and PH2 (RR = 0.41 [95% CI: 0.21, 0.81], P = .01) were associated with decreased chances of good outcome. Conclusion Any degree of intracranial hemorrhage after endovascular treatment was seen in one-third of participants. A graded association existed between radiologic hemorrhage severity and outcome. Hemorrhagic infarction was not associated with outcome, whereas parenchymal hematoma was strongly associated with poor outcome, independent of infarct volume. © RSNA, 2021 Clinical trial registration no. NCT01778335 Online supplemental material is available for this article.

Background Clopidogrel is an inhibitor of the P2Y12 platelet receptor but testing to demonstrate a drug effect is controversial since there are often discordant results between different tests methods. Methods Samples from patients taking clopidogrel prior to intracranial flow-diversion procedures were tested using light transmission aggregometry (LTA), whole blood impedance aggregometry (WBIA) and the VerifyNow device (VND). Samples were classified as concordant if all test results were either responsive (inhibition) or resistant. Discordant results were separated using the VND into those with a responsive versus a resistant test result. Results Samples from 96 patients were studied. Concordance for all three tests was seen in 53/96 (55%) of samples, of which 41 (43%) were responsive and 12 (12%) were resistant. Discordance was observed in 43 samples (45%), 37 (28%) of which were caused by responsive VND and either a resistant WBIA or LTA and 6 (7%) of which were caused by a resistant VND but a responsive test result using either WBIA or LTA. These two discordant groups differed in both platelet count and hematocrit, but no such difference was present between the two concordant groups. Conclusion Discordance in P2Y12 inhibition testing may be partly explained by sample platelet count and hematocrit.

Intro SARS-CoV-2 (COVID-19) infection is associated with acute ischemic stroke (AIS), which may be due to a prothrombotic state. Early reports have suggested high rates of reocclusion following mechanical thrombectomy (MT) with poor radiographic and clinical outcomes. We report our early experience using intra-procedural antithrombotics to address SARS-CoV-2 reocclusion. Methods We identified 6 patients that experienced early reocclusion after MT for COVID-19-associated AIS through retrospective chart review abstracting their basic demographics, COVID-19 status, and stroke management. All these patients were treated after reocclusion with aspirin and cangrelor intra-procedurally, the latter of which was converted to ticagrelor post-procedurally. Some patients additionally received argatroban infusion intraprocedurally. Results Mean age was 54. There were 3 post-procedural and 3 intra-procedural re-occlusions. After repeat thrombectomy and treatment with aspirin and cangrelor, those with post-procedure reocclusion did not show further reocclusion, while those with intra-procedural reocclusion showed radiographic improvement with intraprocedural cangrelor administration. Outcomes for these patients were poor, with a median mRS of 4. Two patients developed petechial hemorrhage of their stroke which was managed conservatively, and one developed a retroperitoneal hemorrhage from femoral access requiring transfusion. There were no patients who developed new parenchymal hematomas. Conclusion COVID-19 AIS may be associated with a hypercoagulable state which risks malignant reocclusion complicating MT. We found antithrombotic treatment periprocedural cangrelor with or without argatroban transitioned to oral aspirin with ticagrelor to be a viable method for management of these patients.

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion can be achieved, while in cases with failed reperfusion, EVT may cause harm, as procedure-related complications may occur. We hypothesized that EVT with failed recanalization does not result in worse outcomes compared to best medical management and compared clinical outcomes of LVO stroke patients who underwent EVT with failed reperfusion to those who were treated with best medical management.We included patients with failed reperfusion from the control (EVT-only) arm of the ESCAPE-NA1 trial and the EVT arm of the ESCAPE trial and patients of the ESCAPE control arm who were treated with best medical management. Failed reperfusion following EVT was defined as modified thrombolysis in cerebral infarction score 0-2a. Proportions of good outcome (modified Rankin scale 0-2) were compared between patients who did and did not undergo EVT, and adjusted effect size estimates for EVT on outcomes were obtained.We included 260 patients (110 failed EVT and 150 non-EVT patients). Proportions of good outcome were 38/110 (34.6%) with failed EVT vs.43/147 (29.3%) without EVT (adjusted odds ratio[aOR]: 1.48 [95%CI: 0.81-2.68]). Mortality and proportions of sICH in the failed EVT group vs. patients treated with best medical management were 26/110 (23.6%) vs. 28/147 (19.1%), aOR: 1.12 (95%CI: 0.56-2.24), and 7/110 (6.4%) vs. 4/150 (2.7%), aOR: 2.34 (95%CI: 0.00-22.97).Clinical outcomes of EVT patients with failed reperfusion did not differ significantly from patients treated with best medical management.

There are few data on the prevalence and impact of isolated deep grey matter infarction in acute stroke. In this study, we aimed to investigate the prevalence of isolated deep grey matter infarcts and their impact on the outcome.Infarcts on 24-h follow-up imaging (non-contrast head CT or diffusion-weighted MRI) in the ESCAPE-NA1 trial were categorized into predominantly deep grey matter infarcts vs. infarcts involving additional territories ("other infarcts"). Total infarct volume was manually segmented. Baseline characteristics and proportions of good outcome (primary outcome, defined as modified Rankin Score [mRS] 0-2 at 90 days), excellent outcome (mRS 0-1) and mortality were compared between patients with and without predominantly deep grey matter infarcts. Multivariable logistic regression with adjustment for baseline variables and total infarct volume was used to determine a possible association of predominantly deep grey matter infarcts and clinical outcome.Predominantly deep grey matter infarcts were seen in 316/1026 patients (30.8%). Compared to other patients, their ASPECTS was higher, collateral status and reperfusion quality were better and time to treatment was shorter. Good outcome was seen in 239/316 (75.6%) with vs. 374/704 (53.1%) without predominantly deep grey matter infarcts. After adjusting for baseline variables and total infarct volume, predominantly deep grey matter infarcts were independently associated with excellent outcome (

Introduction: Carotid web is a putative mechanism of cryptogenic ischemic stroke. We aimed to determine the prevalence of carotid web based on assigned stroke mechanism, and hypothesized that carotid webs would be found more frequently in younger cryptogenic stroke patients. Methods: We performed a single-center retrospective cohort study using institutional registry data from consecutive patients with confirmed anterior circulation ischemic stroke between July 2015-September 2017. We reviewed all available computed tomography angiogram (CTA) studies of the neck, and excluded patients who did not have a high-quality CTA of the neck performed. Carotid web was defined as a thin shelf of non-calcified tissue protruding into the lumen of the internal carotid artery immediately distal to the bifurcation, best visualized on sagittal oblique imaging and evident as a small septum on axial imaging. Stroke subtype was adjudicated a priori using validated methods, and we compared relevant risk factors in patients with cryptogenic stroke with and without carotid web. Results: We identified 882 patients with anterior circulation stroke who had a CTA neck available for review (49.3% male, 30% cryptogenic). A total of 7 patients (0.8%) were found to have carotid webs, of which 4 were ipsilateral to a patient’s stroke; all patients with ipsilateral carotid webs were adjudicated to have cryptogenic stroke. Patients with carotid web were younger than other patients in our cohort (age 49.0±14.6 vs. 72.2±14.9 years, p=0.003), and none of them had a history of hypertension (0% vs. 72%, p=0.04). In patients with cryptogenic stroke, overall prevalence of carotid webs was 1.5%, but the prevalence was significantly higher in younger cryptogenic stroke patients (age Discussion: Carotid web may represent an under-recognized occult mechanism of cryptogenic stroke, particularly amongst younger patients.

Stroke is a major cause of death and disability in the United States and rapid evaluation and treatment of stroke patients are critical to good outcomes. Effective surgical treatments aim to restore adequate cerebral blood flow, prevent secondary brain injury, or reduce the likelihood of recurrent stroke. Patient evaluation in centers with a comprehensive stroke program and a dedicated neuro- vascular team is recommended. [Full article available at http://rimed.org/rimedicaljournal-2017-06.asp].

Dural arteriovenous fistulae (DAVF) are cerebrovascular lesions with pathologic shunting into the venous system from arterial feeders. Digital subtraction angiography (DSA) has long been considered the gold standard for diagnosis, but advances in noninvasive imaging techniques now play a role in the diagnosis of these complex lesions. Herein, we describe the case of a patient with right-side pulsatile tinnitus and DAVF diagnosed using computed tomography angiography, magnetic resonance with arterial spin labeling, and DSA. Implications for imaging analysis of DAVFs and further research are discussed.

Introduction: The double-stranded AAV (dsAAV) vector is a new entity in the field of AAV based technologies. DsAAVs bypass a key requirement of AAV mediated transduction-conversion of the single stranded AAV genome into a double-stranded DNA template capable of RNA transcription. Currently, the only reported method for efficient and practical synthesis of double-stranded AAV's involves a standard AAV plasmid that has had one of its two AAV-inverted terminal repeat sequences mutated. Here we report a novel and practical method to synthesize double-stranded AAV vectors with a slightly increased packaging capacity as compared to the recently published technique.