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The recent advent of endovascular procedures has created the unique opportunity to collect and analyze thrombi removed from cerebral arteries, instigating a novel subfield in stroke research. Insights into thrombus characteristics and composition could play an important role in ongoing efforts to improve acute ischemic stroke therapy. An increasing number of centers are collecting stroke thrombi. This paper aims at providing guiding information on thrombus handling, procedures, and analysis in order to facilitate and standardize this emerging research field. [ABSTRACT FROM AUTHOR]

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset., Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset., Design, Setting, and Participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at 47 US academic and community-based stroke thrombectomy centers. Three hundred patients presenting within 24 hours with anterior-circulation, large-vessel occlusion and large infarct on noncontrast CT scan, with Alberta Stroke Program Early CT Scores of 2 to 5, were randomized to undergo thrombectomy or usual care. Enrollment occurred July 16, 2019 to October 17, 2022; final follow-up, January 25, 2023., Intervention: The intervention patients (n = 152) underwent endovascular treatment using standard thrombectomy devices and usual medical care. Control patients (n = 148) underwent usual medical care alone., Main Outcomes and Measures: The primary efficacy end point was improvement in 90-day functional outcome measured using mean utility-weighted modified Rankin Scale (UW-mRS) scores (range, 0 [death or severe disability] to 10 [no symptoms]; minimum clinically important difference, 0.3). A bayesian model determined the posterior probability that the intervention would be superior to usual care; statistical significance was a 1-sided posterior probability of .975 or more. The primary adverse event end point was 90-day mortality; secondary adverse event end points included symptomatic intracranial hemorrhage and radiographic intracranial hemorrhage., Results: The trial enrolled 300 patients (152 intervention, 148 control; 138 females [46%]; median age, 67 years), without early stopping or enrichment; 297 patients completed the 90-day follow-up. The mean (SD) 90-day UW-mRS score was 2.93 (3.39) for the intervention group vs 2.27 (2.98) for the control group with an adjusted difference of 0.63 (95% credible interval [CrI], -0.09 to 1.34; posterior probability for superiority of thrombectomy, .96). The 90-day mortality was similar between groups: 35.3% (53 of 150) for the intervention group vs 33.3% (49 of 147) for the control group. Six of 151 patients (4.0%) in the intervention group and 2 of 149 (1.3%) in the control group experienced 24-hour symptomatic intracranial hemorrhage. Fourteen patients of 148 (9.5%) in the intervention group vs 4 of 146 (2.7%) in the control group experienced parenchymal hematoma type 1 hemorrhages; 14 (9.5%) in the intervention group vs 5 (3.4%) in the control group experienced parenchymal hematoma type 2 hemorrhages; and 24 (16.2%) in the intervention group vs 9 (6.2%) in the control group experienced subarachnoid hemorrhages., Conclusions and Relevance: Among patients with a large infarct on noncontrast CT within 24 hours, thrombectomy did not demonstrate improvement in functional outcomes. But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study., Trial Registration: ClinicalTrials.gov Identifier: NCT03805308.

Background: The extended Thrombolysis in Cerebral Infarction (eTICI) score is used in digital subtraction angiography (DSA) to quantify reperfusion grade in patients with an ischemic stroke who undergo endovascular thrombectomy (EVT). A previously developed automatic TICI score (autoTICI), which quantifies the ratio of reperfused pixels after EVT, demonstrates good correlation with eTICI., Objective: To evaluate the autoTICI model in a large multicenter registry of patients with an ischemic stroke, investigate the association with visual eTICI, and compare prediction of functional outcome between autoTICI and eTICI., Methods: Patients in the MR CLEAN Registry with an internal carotid artery, M1, and M2 occlusion were selected if both anteroposterior and lateral views were present in pre- and post-EVT DSA scans. The autoTICI score was compared with eTICI in predicting favorable functional outcome (modified Rankin Scale score 0-2), using area under the receiver operating characteristics curve (AUC) with a multivariable logistic regression model including known prognostic characteristics., Results: In total 421 of 3637 patients were included. AutoTICI was significantly associated with eTICI non-linearly (below 70% cOR=2.3 (95% CI 2.1 to 2.5), above 70% cOR=1.6 (95% CI 1.6 to 1.7) per 10% increment). The AUC of the model predicting favorable functional outcome was similar for autoTICI and eTICI (0.86, 95% CI 0.82 to 0.92 vs 0.86, 95% CI 0.83 to 0.90, P=0.73) and was higher than for a model with prognostic patient characteristics alone (0.86 vs 0.84, P=0.01)., Conclusion: Automatic quantitative assessment of reperfusion after EVT is associated with eTICI, and prediction of functional outcome is similar to that with visual eTICI. Therefore, autoTICI could be used as an alternative or additional review for visual reperfusion assessment to facilitate reproducible and uniform reporting., Competing Interests: Competing interests: Erasmus MC received funds from Stryker® by DD, AvdL, and Bracco Imaging® by DD. Amsterdam UMC received funds from Stryker® for consultations by CM, YR and OB. MUMC received funds from Stryker® and Codman® for consultations by WZ., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Occlusion of the anterior cerebral artery (ACA) is uncommon but may lead to significant disability. The benefit of endovascular treatment (EVT) for ACA occlusions remains uncertain., Methods: We included patients treated with EVT and compared patients with ACA occlusions with patients who had internal carotid artery (ICA) or proximal (M1/M2) middle cerebral artery (MCA) occlusions from the MR CLEAN Registry. Primary outcome was the modified Rankin Scale score (mRS). Secondary outcomes were functional independence (mRS 0-2), National Institutes of Health Stroke Scale (NIHSS) score, delta-NIHSS (baseline minus NIHSS score at 24-48 h), and successful recanalization (expanded thrombolysis in cerebral infarction (eTICI) score 2b-3). Safety outcomes were symptomatic intracranial hemorrhage (sICH), periprocedural complications, and mortality., Results: Of 5193 patients, 11 (0.2%) had primary ACA occlusions. Median NIHSS at baseline was lower in patients with ACA versus ICA/MCA occlusions (11, IQR 9-14; versus 15, IQR 11-19). Functional outcome did not differ from patients with ICA/MCA occlusions. Functional independence was 4/11 (36%) in patients with ACA versus 1949/4815 (41%) in ICA/MCA occlusions; median delta-NIHSS was - 1 (IQR - 7 to 2) and - 4 (IQR - 9 to 0), respectively. Successful recanalization was 4/9 (44%), versus 3083/4787 (64%) in ICA/MCA occlusions. Mortality was 3/11 (27%) versus 1263/4815 (26%). One patient with ACA occlusion had sICH; no other complications occurred., Conclusion: In this cohort ACA occlusions were uncommon. Functional outcome did not differ between patients with ACA occlusions and ICA/MCA occlusions. Prospective research is needed to determine feasibility, safety, and outcomes of EVT for ACA occlusions., (© 2023. The Author(s).)

Background: Computed tomography perfusion (CTP)-estimated core volume is associated with functional outcomes in acute ischemic stroke. This relationship might differ among patients, depending on brain volume., Materials and Methods: We retrospectively included patients from the MR CLEAN Registry. Cerebrospinal fluid (CSF) and intracranial volume (ICV) were automatically segmented on NCCT. We defined the proportion of the ICV and total brain volume (TBV) affected by the ischemic core as ICV core and TBV core . Associations between the core volume, ICV core , TBV core , and functional outcome are reported per interquartile range (IQR). We calculated the area under the curve (AUC) to assess diagnostic accuracy., Results: In 200 patients, the median core volume was 13 (5-41) mL. Median ICV and TBV were 1377 (1283-1456) mL and 1108 (1020-1197) mL. Median ICV core and TBV core were 0.9 (0.4-2.8)% and 1.7 (0.5-3.6)%. Core volume (acOR per IQR 0.48 [95%CI 0.33-0.69]), ICV core (acOR per IQR 0.50 [95%CI 0.35-0.69]), and TBV core (acOR per IQR 0.41 95%CI 0.33-0.67]) showed a lower likelihood of achieving improved functional outcomes after 90 days. The AUC was 0.80 for the prediction of functional independence at 90 days for the CTP-estimated core volume, the ICV core , and the TBV core ., Conclusion: Correcting the CTP-estimated core volume for the intracranial or total brain volume did not improve the association with functional outcomes in patients who underwent EVT.

Purpose: Endovascular treatment (EVT) of acute ischemic stroke can be complicated by vessel perforation. We studied the incidence and determinants of vessel perforations. In addition, we studied the association of vessel perforations with functional outcome, and the association between location of perforation on digital subtraction angiography (DSA) and functional outcome, using a large EVT registry., Methods: We included all patients in the MR CLEAN Registry who underwent EVT. We used DSA to determine whether EVT was complicated by a vessel perforation. We analyzed the association with baseline clinical and interventional parameters using logistic regression models. Functional outcome was measured using the modified Rankin Scale at 90 days. The association between vessel perforation and angiographic imaging features and functional outcome was studied using ordinal logistic regression models adjusted for prognostic parameters. These associations were expressed as adjusted common odds ratios (acOR)., Results: Vessel perforation occurred in 74 (2.6%) of 2794 patients who underwent EVT. Female sex (aOR 2.0 (95% CI 1.2-3.2)) and distal occlusion locations (aOR 2.2  (95% CI 1.3-3.5)) were associated with increased risk of vessel perforation. Functional outcome was worse in patients with vessel perforation (acOR 0.38 (95% CI 0.23-0.63)) compared to patients without a vessel perforation. No significant association was found between location of perforation and functional outcome., Conclusion: The incidence of vessel perforation during EVT in this cohort was low, but has severe clinical consequences. Female patients and patients treated at distal occlusion locations are at higher risk., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Endovascular therapy (EVT) is the standard treatment for ischemic stroke caused by a large vessel occlusion (LVO). The effectiveness of EVT for distal medium vessel occlusions (MDVOs) is still uncertain, but newer, smaller devices show potential for EVT in MDVOs. The new Solitaire X 3 mm device offers a treatment option for MDVOs. Our study encompassed consecutive cases of primary and secondary MDVOs treated with the Solitaire X 3 mm stent-retriever as first-line EVT device between January and December 2022 at 12 European stroke centers. The primary endpoint was a first-pass near-complete or complete reperfusion, defined as a modified treatment in cerebral infarction (mTICI) score of 2c/3. Additionally, we examined reperfusion results, National Institutes of Health Stroke Scale (NIHSS) scores at 24 h and discharge, device malfunctions, complications and procedural technical parameters. Sixty-eight patients (38 women, mean age 72 ± 14 years) were included in our study. Median NIHSS at admission was 11 (IQR 6-16). In 53 (78%) cases, a primary combined approach was used as the frontline technique. Among all enrolled patients, first-pass mTICI 2c/3 was achieved in 22 (32%) and final mTICI 2c/3 in 46 (67.6%) patients after a median of 1.5 (IQR 1-2) passes. Final reperfusion mTICI 2b/3 was observed in 89.7% of our cases. We observed no device malfunctions. Median NIHSS at discharge was 2 (IQR 0-4), and no symptomatic intracranial hemorrhages were reported. Based on our analysis, the utilization of the Solitaire X 3 mm device appears to be both effective and safe for performing EVT in cases of MDVO stroke.

Background: Women have been reported to have worse outcomes after endovascular treatment (EVT), despite a similar treatment effect in non-clinical trial populations. We aimed to assess sex differences at hospital presentation with respect to workflow metrics, prestroke disability, and presenting clinical symptoms., Methods: We included consecutive patients from the Multicentre Randomised Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in The Netherlands (MR CLEAN) Registry (2014-2018) who received EVT for anterior circulation large vessel occlusion (LVO). We assessed sex differences in workflow metrics, prestroke disability (modified Rankin Scale (mRS) score ≥1), and stroke severity and symptoms according to the National Institutes of Health Stroke Scale (NIHSS) score on hospital admission with logistic and linear regression analyses and calculated the adjusted OR (aOR)., Results: We included 4872 patients (47.6% women). Compared with men, women were older (median age 76 vs 70 years) and less often achieved good functional outcome at 90 days (mRS ≤2: 35.2% vs 46.4%, aOR 0.70, 95% CI 0.60 to 0.82). Mean onset-to-door time was longer in women (2 hours 16 min vs 2 hours 7 min, adjusted delay 9 min, 95% CI 4 to 13). This delay contributed to longer onset-to-groin times (3 hours 26 min in women vs 3 hours 13 min in men, adjusted delay 13 min, 95% CI 9 to 17). Women more often had prestroke disability (mRS ≥1: 41.1% vs 29.1%, aOR 1.57, 95% CI 1.36 to 1.82). NIHSS on admission was essentially similar in men and women (mean 15±6 vs 15±6, NIHSS <10 vs ≥10, aOR 0.91, 95% CI 0.78 to 1.06). There were no clear sex differences in the occurrence of specific stroke symptoms., Conclusion: Women with LVO had longer onset-to-door times and more often prestroke disability than men. Raising awareness of these differences at hospital presentation and investigating underlying causes may help to improve outcome after EVT in women., Competing Interests: Competing interests: MJHW reports funding from the Dutch Research Council (VIDI grant 91717337). CBLMM reports funding from the TWIN Foundation, CVON/Dutch Heart Foundation, European Commission, Health Evaluation Netherlands, and Stryker, all outside the submitted work (paid to institution); he is shareholder of Nicolab. DWJD reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences and Health, and unrestricted grants from Penumbra Inc, Stryker European Operations BV, Medtronic, Thrombolytic Science, and Cerenovus, all paid to institution. JH reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, and ZonMw, all paid to institution. IRvdW reports funding from Jacobus Stichting. PJN reports funding from the Dutch Heart Foundation and The Netherlands Organisation for Health Research and Development, both paid to institution., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: It is unknown if ambulance paramedics adequately assess neurological deficits used for prehospital stroke scales to detect anterior large-vessel occlusions. We aimed to compare prehospital assessment of these stroke-related deficits by paramedics with in-hospital assessment by physicians., Methods: We used data from 2 prospective cohort studies: the LPSS (Leiden Prehospital Stroke Study) and PRESTO study (Prehospital Triage of Patients With Suspected Stroke). In both studies, paramedics scored 9 neurological deficits in stroke code patients in the field. Trained physicians scored the National Institutes of Health Stroke Scale (NIHSS) at hospital presentation. Patients with transient ischemic attack were excluded because of the transient nature of symptoms. Spearman rank correlation coefficient (r s ) was used to assess correlation between the total prehospital assessment score, defined as the sum of all prehospital items, and the total NIHSS score. Correlation, sensitivity and specificity were calculated for each prehospital item with the corresponding NIHSS item as reference., Results: We included 2850 stroke code patients. Of these, 1528 had ischemic stroke, 243 intracranial hemorrhage, and 1079 stroke mimics. Correlation between the total prehospital assessment score and NIHSS score was strong (r s =0.70 [95% CI, 0.68-0.72]). Concerning individual items, prehospital assessment of arm (r s =0.68) and leg (r s =0.64) motor function correlated strongest with corresponding NIHSS items, and had highest sensitivity (arm 95%, leg 93%) and moderate specificity (arm 71%, leg 70%). Neglect (r s =0.31), abnormal speech (r s =0.50), and gaze deviation (r s =0.51) had weakest correlations. Neglect and gaze deviation had lowest sensitivity (52% and 66%) but high specificity (84% and 89%), while abnormal speech had high sensitivity (85%) but lowest specificity (65%)., Conclusions: The overall prehospital assessment of stroke code patients correlates strongly with in-hospital assessment. Prehospital assessment of neglect, abnormal speech, and gaze deviation differed most from in-hospital assessment. Focused training on these deficits may improve prehospital triage., Competing Interests: Disclosures Dr Kruyt reported receiving grant HA20 15.01.02 from the Dutch Brain Foundation, grant 3.240 from the Dutch Innovation Funds, and grant LSHM16041 from Health~Holland during the conduct of the study. Dr Roozenbeek reported funding from the Dutch Heart Foundation and the Netherlands Organization for Health Research and Development (ZonMw) during the conduct of this study, paid to the institution. Dr Wermer reported receiving Clinical Established Investigator grant 2016T086 from the Dutch Heart Foundation and VIDI grant 9171337 from the Netherlands Organization for Health Research and Development (ZonMw) during the conduct of the original LPSS study (Leiden Prehospital Stroke Study). Dr Dippel reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, the Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences and Health, and unrestricted grants from Penumbra Inc, Stryker, Medtronic, Thrombolytic Science, LLC, and Cerenovus for research, all paid to institution outside the submitted work. Dr van den Wijngaard reports compensation from Philips and Medtronic for consultant services, and stock holdings in Neurophyxia BV. The other authors report no conflicts.

Background: Cerebral amyloid angiopathy (CAA) is a disease caused by the accumulation of the amyloid-beta protein and is a major cause of intracerebral hemorrhage (ICH) and vascular dementia in the elderly. The presence of the amyloid-beta protein in the vessel wall may induce a chronic state of cerebral inflammation by activating astrocytes, microglia, and pro-inflammatory substances. Minocycline, an antibiotic of the tetracycline family, is known to modulate inflammation, gelatinase activity, and angiogenesis. These processes are suggested to be key mechanisms in CAA pathology. Our aim is to show the target engagement of minocycline and investigate in a double-blind placebo-controlled randomized clinical trial whether treatment with minocycline for 3 months can decrease markers of neuroinflammation and of the gelatinase pathway in cerebrospinal fluid (CSF) in CAA patients., Methods: The BATMAN study population consists of 60 persons: 30 persons with hereditary Dutch type CAA (D-CAA) and 30 persons with sporadic CAA. They will be randomized for either placebo or minocycline (15 sporadic CAA/15 D-CAA minocycline, 15 sporadic CAA/15 D-CAA placebo). At t = 0 and t = 3 months, we will collect CSF and blood samples, perform a 7-T MRI, and collect demographic characteristics., Discussion: The results of this proof-of-principle study will be used to assess the potential of target engagement of minocycline for CAA. Therefore, our primary outcome measures are markers of neuroinflammation (IL-6, MCP-1, and IBA-1) and of the gelatinase pathway (MMP2/9 and VEGF) in CSF. Secondly, we will look at the progression of hemorrhagic markers on 7-T MRI before and after treatment and investigate serum biomarkers., Trial Registration: ClinicalTrials.gov NCT05680389. Registered on January 11, 2023., (© 2023. The Author(s).)

Background: Successful recanalization and good collateral status are associated with good clinical outcomes after endovascular treatment (EVT) for acute ischemic stroke, but the relationships among them are unclear., Objective: To assess if collateral status is associated with recanalization after EVT and if collateral status modifies the association between successful recanalization and functional outcome., Methods: We retrospectively analyzed data from the MR CLEAN Registry, a multicenter prospective cohort study of patients with a proximal anterior occlusion who underwent EVT in the Netherlands. We determined collateral status with a previously validated four-point visual grading scale and defined successful recanalization as an extended Thrombolysis in Cerebral Infarction score ≥2B. Functional outcome was determined using the modified Rankin Scale score at 90 days. We assessed, with multivariable logistic regression models, the associations between (1) collateral status and successful recanalization, (2) successful recanalization and functional outcome, (3) collateral status and functional outcome. An interaction of collateral status and successful recanalization was assessed. Subgroup analyses were performed for patients treated with intravenous thrombolysis., Results: We included 2717 patients, of whom 1898 (70%) had successful recanalization. There was no relationship between collateral status and successful recanalization (adjusted common OR (95% CI) of grades 1, 2, and 3 vs 0: 1.19 (0.82 to 1.72), 1.20 (0.83 to 1.75), and 1.10 (0.74 to 1.63), respectively). Successful recanalization (acOR (95% CI): 2.15 (1.84 to 2.52)) and better collateral grades (acOR (95% CI) of grades 1, 2, and 3 vs 0: 2.12 (1.47 to 3.05), 3.46 (2.43 to 4.92), and 4.16 (2.89 to 5.99), respectively) were both associated with a shift towards better functional outcome, without an interaction between collateral status and successful recanalization. Results were similar for the subgroup of thrombolysed patients., Conclusions: Collateral status is not associated with the probability of successful recanalization after EVT and does not modify the association between successful recanalization and functional outcome., Competing Interests: Competing interests: Simone M. Uniken Venema, Jan Willem Dankbaar, Lennard Wolff, Adriaan C. G. M. van Es, Marieke Sprengers report no disclosures; Diederik W. J. Dippel: reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences and Health, and unrestricted grants from Penumbra Inc., Stryker, Medtronic, Cerenovus and Thrombolytic Science, LLC for research, all paid to his institution; Aad van der Lugt: reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences and Health, and unrestricted grants from Penumbra Inc., Stryker, Medtronic, Cerenovus, and Thrombolytic Science, LLC for research, all paid to his institution; H. Bart van der Worp: received fees for consultation for Bayer and LivaNova, all paid to his institution., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Endovascular thrombectomy (EVT) through femoral access is difficult to perform in some patients with acute ischemic stroke due to challenging vasculature. We compared outcomes of EVT through femoral versus alternative arterial access. Methods: In this observational study, we included patients from the MR CLEAN Registry who underwent EVT for acute ischemic stroke in the anterior circulation between 2014 and 2019 in the Netherlands. Patients who underwent EVT through alternative and femoral access were matched on propensity scores in a 1:3 ratio. The primary endpoint was favorable functional outcome (modified Rankin Scale score ≤ 2) at 90 days. Secondary endpoints were early neurologic recovery, mortality, successful intracranial reperfusion and puncture related complications. Results: Of the 5197 included patients, 17 patients underwent EVT through alternative access and were matched to 48 patients who underwent EVT through femoral access. Alternative access was obtained through the common carotid artery (n = 15/17) and brachial artery (n = 2/17). Favorable functional outcome was less often observed after EVT through alternative than femoral access (18% versus 27%; aOR, 0.36; 95% CI, 0.05-2.74). The rate of successful intracranial reperfusion was higher for alternative than femoral access (88% versus 58%), although mortality (59% versus 31%) and puncture related complications (29% versus 0%) were more common after alternative access. Conclusions: EVT through alternative arterial access is rarely performed in the Netherlands and seems to be associated with worse outcomes than standard femoral access. A next step would be to compare the additional value of EVT through alternative arterial access after failure of femoral access.

Purpose: The composition of thrombi retrieved during endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) may differ depending on their origin. In this study, we investigated the association between thrombus composition and stroke etiology in a large population of patients from the Dutch MR CLEAN Registry treated with EVT in daily clinical practice., Methods: The thrombi of 332 patients with AIS were histologically analyzed for red blood cells (RBC), fibrin/platelets (F/P), and white blood cells (leukocytes) using a machine learning algorithm. Stroke etiology was assessed using the Trial of Org 10,172 in acute stroke treatment (TOAST) classification., Results: The thrombi of cardioembolic origin contained less RBC and more F/P than those of non-cardioembolic origin (25.8% vs 41.2% RBC [p = 0.003] and 67.1% vs 54.5% F/P [p = 0.004]). The likelihood of a non-cardioembolic source of stroke increased with increasing thrombus RBC content (OR 1.02; [95% CI 1.00-1.06] for each percent increase) and decreased with a higher F/P content (OR 1.02; [95% CI 1.00-1.06]). Thrombus composition in patients with a cardioembolic origin and undetermined origin was similar., Conclusion: Thrombus composition is significantly associated with stroke etiology, with an increase in RBC and a decrease in F/P raising the odds for a non-cardioembolic cause. No difference between composition of cardioembolic thrombi and of undetermined origin was seen. This emphasizes the need for more extensive monitoring for arrhythmias and/or extended cardiac analysis in case of an undetermined origin., (© 2023. The Author(s).)

Background: Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA)., Methods: MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220., Findings: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10])., Interpretation: In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow., Funding: Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation., Competing Interests: Declaration of interests RJvO and WHvZ report financial support for the current manuscript from the Collaboration for New Treatments of Acute Stroke (CONTRAST) consortium (which was financed for the current study by the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation, the Netherlands Brain Foundation, Stryker, Medtronic, and Cerenovus), all paid to their institution. WHvZ reports speaker fees from Stryker, Cerenovus, and Nicolab, and consulting fees from Philips, all paid to institution; participated in the advisory boards of WeTrust (Philips) and ANAIS (Anaconda), all paid to institution; and participated in the advisory boards of InEcxtremis (CHU Montpellier, Montpellier, France) and DISTAL (University Hospital Basel, Basel, Switzerland), studies for which no payments were received. AvdL reports financial support for this study by grants from the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation, the Netherlands Brain Foundation, Medtronic, and Cerenovus, all paid to institution; reports grants from Stryker, Thrombolytic Science, Penumbra, GE Healthcare, Philips Healthcare, and Siemens Healthineers, all paid to institution; reports payments from Siemens Healthineers, all paid to institution; participates in the advisory board of ESCAPE-MEVO; and is a research leader of the CONTRAST consortium. CBLMM reports grants from the Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation, TWIN Foundation, European Commission, Healthcare Evaluation Netherlands, and Stryker (all paid to institution); and is a (minority interest) shareholder of Nicolab. MU reports research grants from the Dutch Heart Foundation, the Netherlands Organisation for Health Research and Development, and Belgian Health Care Knowledge Centre, all paid to institution; and support to attend the Stroke Symposium Johnson & Johnson 2022. BR reports being the chair of the Writing Committee of the Dutch Stroke Guideline. DWJD reports funding from the Dutch Heart Foundation, Netherlands Brain Foundation, the Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, Penumbra, Stryker, Medtronic, Thrombolytic Science, and Cerenovus (all unrestricted grants for research), paid to institution. JMC reports receiving research support from Bayer, AstraZeneca, and Medtronic for research, all paid to institution; and is a co-founder and shareholder of TrianecT. HDB reports consulting fees from Stryker Neurovascular, all paid to institution. AAP reports institutional grants from Siemens Healthcare and Bayer Healthcare, paid to institution. BJE reports funding from the Netherlands Organisation for Health Research and Development and Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Nicolab, all paid to institution. HBvdW reports research grants from the Dutch Heart Foundation, European Commission, and Stryker; consultancy fees from Bayer and TargED, all paid to institution; and stocks in Philips. RPHB reports research grants from the Netherlands Organisation for Health Research and Developmen and the Dutch Ministry of Economic Affairs and Climate Policy, an unrestricted grant from Siemens Healthineers, and consulting fees from Guerbet, all paid to institution. P-JvD reports consulting fees from Stryker and Philips, all paid to institution. YBWEMR reports being a minor shareholder of Nicolab. IRvdW reports consulting fees from Philips (paid to IRvdW) and is a stockholder and inventor of a patent owned by Neurophyxia. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Endovascular treatment (EVT) is standard of care in anterior circulation large vessel occlusions. In posterior circulation occlusions, data on EVT in isolated posterior cerebral artery (PCA) occlusions are limited, although PCA occlusions can cause severe neurological deficit., Objective: To describe in a prospective study the clinical manifestations, outcomes, and safety of EVT in isolated PCA occlusions., Methods: We used data (2014-2017) from the MR CLEAN Registry, a nationwide, prospective cohort of EVT-treated patients in the Netherlands. We included patients with acute ischemic stroke (AIS) due to an isolated PCA occlusion on CT angiography. Patients with concurrent occlusion of the basilar artery were excluded. Outcomes included change in National Institutes of Health Stroke Scale (ΔNIHSS) score, modified Rankin Scale (mRS) score 0-3 after 90 days, mortality, expanded Thrombolysis in Cerebral Infarction (eTICI), and periprocedural complications., Results: Twenty (12%) of 162 patients with posterior circulation occlusions had an isolated PCA occlusion. Median age was 72 years; 13 (65%) were women. Median baseline NIHSS score was 13 (IQR 5-21). Six (30%) patients were comatose. Twelve patients (60%) received IVT. Median ΔNIHSS was -4 (IQR -11-+1). At follow-up, nine patients (45%) had mRS score 0-3. Seven (35%) died. eTICI 2b-3 was achieved in 13 patients (65%). Nine patients (45%) had periprocedural complications. No symptomatic intracranial hemorrhages (sICH) occurred., Conclusions: EVT should be considered in selected patients with AIS with an isolated PCA occlusion, presenting with moderate-severe neurological deficits, as EVT was technically feasible in most of our patients and about half had good clinical outcome. In case of lower NIHSS score, a more conservative approach seems warranted, since periprocedural complications are not uncommon. Nonetheless, EVT seems reasonably safe considering the absence of sICH in our study., Competing Interests: Competing interests: CBLMM and YBWEMR received funds from the Applied Scientific Institute for Neuromodulation (Toegepast Wetenschappelijk Instituut voor Neuromodulatie - TWIN) Foundation (related to this project, paid to institution). CBLMM received funds from CVON/Dutch Heart Foundation, Stryker, European Commission, Health Evaluation Netherlands (unrelated; all paid to institution). DWJD and AvdL received research grants from Dutch Heart Foundation, Brain Foundation Netherlands, the Netherlands Organisation for Health Research and Development and Health Holland Top Sector Life Sciences and Health, and unrestricted grants from AngioCare BV, Medtronic/Covidien/EV3, Medac Gmbh/Lamepro, Penumbra Inc, Stryker, Top Medical/Concentric, Thrombolytic Science LLC, Stryker European Operations BV and Cerenovus. YBWEMR and CBLMM are shareholders of Nico.laboratory. CBLMM, YBWEMR, and JMC were principal investigators of the MR CLEAN NO IV trial. DWJD and AvdL were principal investigators of the MR CLEAN MED trial. JMC reports grants from Medtronic, Boehringer Ingelheim, and Bayer outside the submitted work., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Current guidelines for ischaemic stroke treatment recommend a strict, but arbitrary, upper threshold of 185/110 mm Hg for blood pressure before endovascular thrombectomy. Nevertheless, whether admission blood pressure influences the effect of endovascular thrombectomy on outcome remains unknown. Our aim was to study the influence of admission systolic blood pressure (SBP) on functional outcome and on the effect of endovascular thrombectomy., Methods: We used individual patient data from seven randomised controlled trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, PISTE, and THRACE) that randomly assigned patients with anterior circulation ischaemic stroke to endovascular thrombectomy (predominantly using stent retrievers) or standard medical therapy (control) between June 1, 2010, and April 30, 2015. We included all patients for whom SBP data were available at hospital admission. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. We assessed the association of SBP with outcome in both the endovascular thrombectomy group and the control group using multilevel regression analysis and tested for non-linearity and for interaction between SBP and effect of endovascular thrombectomy, taking into account treatment with intravenous thrombolysis., Findings: We included 1753 patients (867 assigned to endovascular thrombectomy, 886 assigned to control) after excluding 11 patients for whom SBP data were missing. We found a non-linear association between SBP and functional outcome with an inflection point at 140 mm Hg (732 [42%] of 1753 patients had SBP <140 mm Hg and 1021 [58%] had SBP ≥140 mm Hg). Among patients with SBP of 140 mm Hg or higher, admission SBP was associated with worse functional outcome (adjusted common odds ratio [acOR] 0·86 per 10 mm Hg SBP increase; 95% CI 0·81-0·91). We found no association between SBP and functional outcome in patients with SBP less than 140 mm Hg (acOR 0·97 per 10 mm Hg SBP decrease, 95% CI 0·88-1·05). There was no significant interaction between SBP and effect of endovascular thrombectomy on functional outcome (p=0·96)., Interpretation: In our meta-analysis, high admission SBP was associated with worse functional outcome after stroke, but SBP did not seem to negate the effect of endovascular thrombectomy. This finding suggests that admission SBP should not form the basis for decisions to withhold or delay endovascular thrombectomy for ischaemic stroke, but randomised trials are needed to further investigate this possibility., Funding: Medtronic., Competing Interests: Declaration of interests SB reports personal fees from the University of Calgary during the conduct of the HERMES collaboration and membership on a data safety monitoring board (DSMB) for the TESLA trial, no payment accepted. MG reports that Medtronic, NoNO, and Cerenovus provided a grant to the University of Calgary; royalties or licenses from GE Healthcare for systems of acute stroke diagnosis and Microventric for systems of intracranial access; consulting fees from Medtronic, Microvention, Stryker, and Mentice; and holds stock in Circle Neurovascular. KWM reports a grant from Boehringer Ingelheim payed to the institution for support of the ATTEST-2 trial; consulting fees from Boehringer Ingelheim, AbbVie, and Biogen; and BHF-funded DSMB participation (ARREST trial). PMW reports unrestricted grants from Stryker, Medtronic (Covidien), and Penumbra payed to the institution. TGJ reports honoraria from Stryker, Silk Road Medical, Blockade Medical, FreeOx Biomedical, Route 92, Neurotrauma Science, Viz.ai, Corindus, Anaconda, Medtronic, Contego, and Methinks as a consultant; and has consulted for Cerenovus as a steering committee member and Stryker Neurovascular as a principal investigator of DAWN and AURORA. MDH reports a research grant from Medtronic paid to the University of Calgary for the HERMES collaboration; grants all paid to the University of Calgary from Boehringer-Ingelheim (for the TEMPO-2 trial), Biogen, NoNO (for the ESCAPE-NA1 trial, ESCAPE-NEXT trial), Canadian Institutes for Health Research (for the ESCAPE-NA1 trial, ESCAPE-NEXT trial), and Alberta Innovates (for the QuICR Alberta Stroke Program; some of the funds were used for the ESCAPE-NA1 trial). MDH also reports paid work for Sun Pharma and Brainsgate for adjudication of clinical trial outcomes; patents (US Patent 62/086,077 and US Patent 10,916,346) licensed to Circle NVI; and participation as a DSMB chair for the RACECAT trial (end 2020), Oncovir Hiltonel trial (ongoing), and DUMAS trial (ongoing), and DSMB member for the ARTESIA trial (ongoing) and BRAIN-AF trial (ongoing). MDH is president of the Canadian Neurological Sciences Federation (not for profit), board member of the Canadian Stroke Consortium (not for profit), and holds stock in Circle and PureWeb. PJM reports speaking engagements from Stryker and Medtronic and research institutional support from Stryker Neurovascular and Medtronic. AMD reports honoraria from Medtronic, grants from Cerenovus for the ENDOLOW trial, and participated in a DSMB for the WE-TRUST trial (Philips). DWJD reports unrestricted research grants from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences and Health, and unrestricted grants from Medtronic, Penumbra, Stryker, Thrombolytic Science, and Cerenovus (all paid to institution). AvdL reports grants from Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences & Health, Stryker, Penumbra, Medtronic, Cerenovus, Thrombolytic Science, GE Healthcare, Siemens Healthineers, and Philips Healthcare (all paid to his institution). AvdL also reports speaking fees from Siemens Healthineers paid to the institution, participation on a DSMB for the ESCAPE-MEVO trial, and is research leader of CONTRAST consortium (unpaid). All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Higher expanded Treatment In Cerebral Ischemia (eTICI) reperfusion scores after endovascular treatment (EVT) are associated with better outcomes. However, the influence of the number of passes on this association is unclear. We aimed to compare outcomes of single-pass good reperfusion (eTICI 2B) with multiple-pass excellent/complete reperfusion (eTICI 2C/3) in daily clinical practice., Methods: We compared outcomes of patients in the MR CLEAN Registry with good reperfusion (eTICI 2B) in a single pass to those with excellent/complete reperfusion (eTICI 2C/3) in multiple passes. Regression models were used to investigate the association of single-pass eTICI 2B versus multiple-pass eTICI 2C/3 reperfusion with 90-day functional outcome (modified Rankin Scale (mRS)), functional independence (mRS 0-2), per-procedural complications and safety outcomes., Results: We included 699 patients: 178 patients with single-pass eTICI 2B, and 242 and 279 patients with eTICI 2C/3 after 2 and ≥3 passes, respectively. Patients with eTICI 2C/3 after 2 or ≥3 passes did not achieve significantly better functional outcomes compared with patients with single-pass eTICI 2B (adjusted common OR (acOR) 1.06, 95% CI 0.75 to 1.50 and acOR 0.88, 95% CI 0.74 to 1.05 for 90-day mRS, and adjusted OR (aOR) 1.24, 95% CI 0.78 to 1.97 and aOR 0.79, 95% CI 0.52 to 1.22 for functional independence)., Conclusions: Our results did not show better outcomes for patients who achieved eTICI 2C/3 in multiple, that is, two or more, passes when compared with patients with single-pass eTICI 2B. However, this concerns observational data. Further research is necessary to investigate the per-pass effect in relation to reperfusion and functional outcome., Competing Interests: Competing interests: Amsterdam UMC received funds from Stryker for consultation by CBLM. Unrelated to this study, Amsterdam UMC received grants from the Netherlands Organization for Health Research and Development, Health Holland Top Sector LSH and Nicolab B.V. Erasmus University Medical Center received funds from Stryker, Siemens Healthineers, GE Healthcare and Bracco Imaging for consultation by DWJD. Maastricht University Medical Center received funds from Stryker, Cerenovus, Nicolab B.V. and Philips for consultation by WvZ. JMC reports a grant from Medtronic, all fees paid to institution. HAM is co-founder and shareholder of Nicolab B.V. Dr Charles BLM Majoie reports grants from the TWIN Foundation, CVON/Dutch Heart Foundation, European Commission, Health Evaluation Netherlands, and Stryker, all paid to the institution. CBLM is minor shareholder of Nicolab B.V. Dr Bart J Emmer reports a TKI-Private PPP Grant from the Dutch Ministry of Economics. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Direct transportation to a thrombectomy-capable intervention center is beneficial for patients with ischemic stroke due to large vessel occlusion (LVO), but can delay intravenous thrombolytics (IVT). The aim of this modeling study was to estimate the effect of prehospital triage strategies on treatment delays and overtriage in different regions., Methods: We used data from two prospective cohort studies in the Netherlands: the Leiden Prehospital Stroke Study and the PRESTO study. We included stroke code patients within 6 h from symptom onset. We modeled outcomes of Rapid Arterial oCclusion Evaluation (RACE) scale triage and triage with a personalized decision tool, using drip-and-ship as reference. Main outcomes were overtriage (stroke code patients incorrectly triaged to an intervention center), reduced delay to endovascular thrombectomy (EVT), and delay to IVT., Results: We included 1798 stroke code patients from four ambulance regions. Per region, overtriage ranged from 1-13% (RACE triage) and 3-15% (personalized tool). Reduction of delay to EVT varied by region between 24 ± 5 min ( n  = 6) to 78 ± 3 ( n  = 2), while IVT delay increased with 5 ( n  = 5) to 15 min ( n  = 21) for non-LVO patients. The personalized tool reduced delay to EVT for more patients (25 ± 4 min [ n  = 8] to 49 ± 13 [ n  = 5]), while delaying IVT with 3-14 min (8-24 patients). In region C, most EVT patients were treated faster (reduction of delay to EVT 31 ± 6 min ( n  = 35), with RACE triage and the personalized tool., Conclusions: In this modeling study, we showed that prehospital triage reduced time to EVT without disproportionate IVT delay, compared to a drip-and-ship strategy. The effect of triage strategies and the associated overtriage varied between regions. Implementation of prehospital triage should therefore be considered on a regional level.

Background: The usefulness of prehospital scales for identifying anterior circulation large vessel occlusion (aLVO) in patients with suspected stroke may vary depending on the severity of their presentation. The performance of these scales across the spectrum of deficit severity is unclear. The aim of this study was to evaluate the diagnostic performance of 8 prehospital scales for identifying aLVO across the spectrum of deficit severity., Methods: We used data from the PRESTO study (Prehospital Triage of Patients With Suspected Stroke Symptoms), a prospective observational study comparing prehospital stroke scales in detecting aLVO in suspected stroke patients. We used the National Institutes of Health Stroke Scale (NIHSS) score, assessed in-hospital, as a proxy for the Clinical Global Impression of stroke severity during prehospital assessment by paramedics. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and the difference in aLVO probabilities with a positive or negative prehospital scale test (ΔP aLVO ) for each scale for mild (NIHSS 0-4), intermediate (NIHSS 5-9), moderate (NIHSS 10-14), and severe deficits (NIHSS≥15)., Results: Among 1033 patients with suspected stroke, 119 (11.5%) had an aLVO, of whom 19 (16.0%) had mild, 25 (21.0%) had intermediate, 30 (25.2%) had moderate, and 45 (37.8%) had severe deficits. The scales had low sensitivity and positive predictive value in patients with mild-intermediate deficits, and poor specificity, negative predictive value, and accuracy with moderate-severe deficits. Positive results achieved the highest ΔP aLVO in patients with mild deficits. Negative results achieved the highest ΔP aLVO with severe deficits, but the probability of aLVO with a negative result in the severe range was higher than with a positive test in the mild range., Conclusions: Commonly-used prehospital stroke scales show variable performance across the range of deficit severity. Probability of aLVO remains high with a negative test in severely affected patients. Studies reporting prehospital stroke scale performance should be appraised in the context of the NIHSS distribution of their samples.

Objectives: Thrombus computed tomography (CT) characteristics might be used to assess histopathologic thrombus composition in patients treated with endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). We aimed to assess the variability in thrombus composition that could be predicted with combined thrombus CT characteristics., Methods: Thrombi of patients enrolled in the MR CLEAN Registry between March 2014 and June 2016 were histologically analyzed with hematoxylin-eosin staining and quantified for percentages of red blood cells (RBCs) and fibrin/platelets. We estimated the association between general qualitative characteristics (hyperdense artery sign [HAS], occlusion location, clot burden score [CBS]) and thrombus composition with linear regression, and quantified RBC variability that could be explained with individual and combined characteristics with R 2 . For patients with available thin-slice (≤ 2.5 mm) imaging, we performed similar analyses for general and quantitative characteristics (HAS, occlusion location, CBS, [relative] thrombus density, thrombus length, perviousness, distance from ICA-terminus)., Results: In 332 included patients, the presence of HAS (aβ 7.8 [95% CI 3.9-11.7]) and shift towards a more proximal occlusion location (aβ 3.9 [95% CI 0.6-7.1]) were independently associated with increased RBC and decreased fibrin/platelet content. With general characteristics, 12% of RBC variability could be explained; HAS was the strongest predictor. In 94 patients with available thin-slice imaging, 30% of RBC variability could be explained; thrombus density and thrombus length were the strongest predictors., Conclusions: Quantitative thrombus CT characteristics on thin-slice admission CT improve prediction of thrombus composition and might be used to further guide clinical decision-making in patients treated with EVT for AIS in the future., Key Points: • With hyperdense artery sign and occlusion location, 12% of variability in thrombus RBC content can be explained. • With hyperdense artery sign, occlusion location, and quantitative thrombus characteristics on thin-slice (≤ 2.5 mm) non-contrast CT and CTA, 30% of variability in thrombus RBC content can be explained. • Absolute thrombus density and thrombus length were the strongest predictors for thrombus composition., (© 2022. The Author(s).)

Background and Objectives: Preventive unruptured intracranial aneurysm (UIA) occlusion can reduce the risk of subarachnoid hemorrhage, but both endovascular and microneurosurgical treatment carry a risk of serious complications. To improve individualized management decisions, we developed risk scores for complications of endovascular and microneurosurgical treatment based on easily retrievable patient, aneurysm, and treatment characteristics., Methods: For this multicenter cohort study, we combined individual patient data from patients with UIA aged 18 years or older undergoing preventive endovascular treatment (standard, balloon-assisted or stent-assisted coiling, Woven EndoBridge-device, or flow-diverting stent) or microneurosurgical clipping at one of the 10 participating centers from 3 continents between 2000 and 2018. The primary outcome was death from any cause or clinical deterioration from neurologic complications ≤30 days. We selected predictors based on previous knowledge about relevant risk factors and predictor performance and studied the association between predictors and complications with logistic regression. We assessed model performance with calibration plots and concordance ( c ) statistics., Results: Of the 1,282 included patients, 94 (7.3%) had neurologic symptoms that resolved <30 days, 140 (10.9%) had persisting neurologic symptoms, and 6 died (0.5%). At 30 days, 52 patients (4.1%) were dead or dependent. Predictors of procedural complications were size of aneurysm, aneurysm location, familial subarachnoid hemorrhage, earlier atherosclerotic disease, treatment volume, endovascular modality (for endovascular treatment) or extra aneurysm configuration factors (for microneurosurgical treatment, branching artery from aneurysm neck or unfavorable dome-to-neck ratio), and age (acronym: SAFETEA). For endovascular treatment (n = 752), the c -statistic was 0.72 (95% CI 0.67-0.77) and the absolute complication risk ranged from 3.2% (95% CI 1.6%-14.9%; ≤1 point) to 33.1% (95% CI 25.4%-41.5%; ≥6 points). For microneurosurgical treatment (n = 530), the c -statistic was 0.72 (95% CI 0.67-0.77) and the complication risk ranged from 4.9% (95% CI 1.5%-14.9%; ≤1 point) to 49.9% (95% CI 39.4%-60.6%; ≥6 points)., Discussion: The SAFETEA risk scores for endovascular and microneurosurgical treatment are based on 7 easily retrievable risk factors to predict the absolute risk of procedural complications in patients with UIAs. The scores need external validation before the predicted risks can be properly used to support decision-making in clinical practice., Classification of Evidence: This study provides Class III evidence that SAFETEA scores predict the risk of procedural complications after endovascular and microneurosurgical treatment of unruptured intracranial aneurysms., (© 2022 American Academy of Neurology.)

Objectives: We aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a successful reperfusion after the procedure., Materials and Methods: We performed a post-hoc analysis of the MR CLEAN-MED trial, including adult patients with a large vessel occlusion in the anterior circulation eligible for endovascular treatment (EVT). In this trial, patients were randomized for periprocedural intravenous treatment with aspirin or no aspirin (1:1 ratio), and for moderate-dose unfractionated heparin, low-dose unfractionated heparin or no unfractionated heparin (1:1:1 ratio). We tested for interaction between the post-EVT extended thrombolysis in cerebral infarction (eTICI) score and treatment with periprocedural medication with multivariable regression analyses. The primary outcome was the modified Rankin Scale score at 90 days. Secondary outcomes were final infarct volume, intracranial hemorrhage, and symptomatic intracranial hemorrhage., Results: Of 534 included patients, 93 (17%) had a post-EVT eTICI score of 0-2a, 115 (22%) a score of 2b, 73 (14%) a score of 2c, and 253 (47%) a score of 3. For both aspirin and heparin, we found no interaction between post-EVT eTICI score and treatment on the modified Rankin Scale score (p=0.76 and p=0.47, respectively). We found an interaction between post-EVT eTICI score and treatment with heparin on the final infarct volume (p=0.01). Of note, this interaction showed a biologically implausible distribution over the subgroups., Conclusions: The overall harmful effect of periprocedural aspirin and unfractionated heparin is not different in patients with a successful reperfusion after EVT., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location., Methods: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue., Results: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06-2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02-1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI, 1.16-2.78])., Conclusions: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms., Registration: URL: https://www.isrctn.com/; Unique identifier: ISRCTN10888758.

Background and Objectives: No consensus exists on adequate surveillance of conservatively managed unruptured intracranial aneurysms (UIAs). We aimed to determine optimal MRI surveillance strategies for the growth of UIAs using cost-effectiveness analysis. A secondary aim was to develop a clinical tool for personalizing UIA surveillance., Methods: We designed a microsimulation model from a health care perspective simulating 100,000 55-year-old women to estimate costs and quality-adjusted life years (QALYs) over a lifetime horizon in the United States, the United Kingdom, and the Netherlands, using literature-derived model parameters. Country-specific costs and willingness-to-pay thresholds ($100,000/QALY for the United States, £30,000/QALY for the United Kingdom, and €80,000/QALY for the Netherlands) were used. Lifetime costs and QALYs were annually discounted at 3% for the United States, 3.5% for the United Kingdom, or 4% (costs) and 1.5% (QALYs) for the Netherlands. Strategies were no follow-up surveillance, follow-up with MRI in the first and fifth year after UIA discovery, every 5 years, every 2 years, or annually, or immediate intervention (i.e., clipping or coiling). Using the microsimulation model, we developed a tool for personalizing UIA surveillance for men and women, with different ages and varying aneurysm characteristics. Uncertainty in the input parameters was modeled with probabilistic sensitivity analysis., Results: Among 55-year-old women, 2,222 individuals in the United States, 1,910 in the United Kingdom, and 2,040 in the Netherlands needed to undergo an annual MRI scan to prevent 1 case of subarachnoid hemorrhage per year. No surveillance MRI was most cost-effective in the United States (in 47% of the simulations) and United Kingdom (in 54% of simulations), whereas annual MRI was most cost-effective in the Netherlands (in 53% of simulations). In the United States and United Kingdom, annual surveillance or surveillance in the first and fifth year after discovery was cost-effective in patients <60 years and at increased risk of aneurysm growth. The optimal, personalized, surveillance strategies were summarized in a look-up table for use in clinical practice., Discussion: Generally, the US and UK physicians should refrain from assigning patients, particularly older patients and those with few risk factors for aneurysm growth or rupture, to frequent MRI surveillance. In the Netherlands, annual follow-up is generally most cost-effective., (© 2022 American Academy of Neurology.)

Objectives: Outcome of endovascular treatment in acute ischemic stroke patients depends on collateral circulation to provide blood supply to the ischemic territory. We evaluated the performance of a commercially available algorithm for assessing the collateral score (CS) in acute ischemic stroke patients., Methods: Retrospectively, baseline CTA scans (≤ 3-mm slice thickness) with an intracranial carotid artery (ICA), middle cerebral artery segment M1 or M2 occlusion, from the MR CLEAN Registry (n = 1627) were evaluated. All CTA scans were evaluated for visual CS (0-3) by eight expert radiologists (reference standard). A Web-based AI algorithm quantified the collateral circulation (0-100%) for correctly detected occlusion sides. Agreement between visual CS and categorized automated CS (0: 0%, 1: > 0- ≤ 50%, 2: > 50- < 100%, 3: 100%) was assessed. Area under the curve (AUC) values for classifying patients in having good (CS: 2-3) versus poor (CS: 0-1) collaterals and for predicting functional independence (90-day modified Rankin Scale 0-2) were computed. Influence of CTA acquisition timing after contrast material administration was reported., Results: In the analyzed scans (n = 1024), 59% agreement was found between visual CS and automated CS. An AUC of 0.87 (95% CI: 0.85-0.90) was found for discriminating good versus poor CS. Timing of CTA acquisition did not influence discriminatory performance. AUC for predicting functional independence was 0.66 (95% CI 0.62-0.69) for automated CS, similar to visual CS 0.64 (95% CI 0.61-0.68)., Conclusions: The automated CS performs similar to radiologists in determining a good versus poor collateral score and predicting functional independence in acute ischemic stroke patients with a large vessel occlusion., Key Points: • Software for automated quantification of intracerebral collateral circulation on computed tomography angiography performs similar to expert radiologists in determining a good versus poor collateral score. • Software for automated quantification of intracerebral collateral circulation on computed tomography angiography performs similar to expert radiologists in predicting functional independence in acute ischemic stroke patients with a large vessel occlusion. • The timing of computed tomography angiography acquisition after contrast material administration did not influence the performance of automated quantification of the collateral status., (© 2022. The Author(s).)

Background: Machine learning algorithms hold the potential to contribute to fast and accurate detection of large vessel occlusion (LVO) in patients with suspected acute ischemic stroke. We assessed the diagnostic performance of an automated LVO detection algorithm on CT angiography (CTA)., Methods: Data from the MR CLEAN Registry and PRESTO were used including patients with and without LVO. CTA data were analyzed by the algorithm for detection and localization of LVO (intracranial internal carotid artery (ICA)/ICA terminus (ICA-T), M1, or M2). Assessments done by expert neuroradiologists were used as reference. Diagnostic performance was assessed for detection of LVO and per occlusion location by means of sensitivity, specificity, and area under the curve (AUC)., Results: We analyzed CTAs of 1110 patients from the MR CLEAN Registry (median age (IQR) 71 years (60-80); 584 men; 1110 with LVO) and of 646 patients from PRESTO (median age (IQR) 73 years (62-82); 358 men; 141 with and 505 without LVO). For detection of LVO, the algorithm yielded a sensitivity of 89% in the MR CLEAN Registry and a sensitivity of 72%, specificity of 78%, and AUC of 0.75 in PRESTO. Sensitivity per occlusion location was 88% for ICA/ICA-T, 94% for M1, and 72% for M2 occlusion in the MR CLEAN Registry, and 80% for ICA/ICA-T, 95% for M1, and 49% for M2 occlusion in PRESTO., Conclusion: The algorithm provided a high detection rate for proximal LVO, but performance varied significantly by occlusion location. Detection of M2 occlusion needs further improvement., Competing Interests: Competing interests: WHvZ reports grants from Stryker and Cerenovus, all paid to the institution. DWJD reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences and Health, and unrestricted grants from Penumbra, Stryker, Medtronic, Thrombolytic Science, LLC, and Cerenovus, all paid to the institution. AvdL reports grants from Penumbra, Stryker, Cerenovus, and Medtronic, all paid to the institution., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Awareness campaigns advise the public to call emergency medical services (EMS) directly in case of suspected stroke. We aimed to explore patient and notification characteristics that influence direct EMS notification, the time to alert, and the time to treatment., Methods: We performed a secondary analysis with data from the PRESTO study, a multi-center prospective observational cohort study that included patients with suspected stroke. We used multivariable binary logistic regression analyses to assess the association with direct EMS notification and multivariable linear regression analyses to assess the association with the onset-to-alert time, onset-to-needle time and onset-to-groin time., Results: Of 436 included patients, 208 patients (48%) contacted EMS directly. FAST scores (aOR 1.45 for every point increase, 95%CI: 1.14-1.86), alert outside office hours (aOR 1.64 [1.05-2.55]), and onset-to-alert time (aOR for every minute less [≤55 min]: 0.96 [0.95-0.97]) were independently associated with direct EMS notification. Direct EMS call was independently associated with shorter onset-to-alert times (27 min [54-0.84]) and with shorter onset-to-needle times (-30 min [-51 to -10]). The association between direct EMS call and the onset-to-groin time was almost similar to the association with onset-to-needle time, though not statistically significant (univariable analysis: 23.7 min decrease [-103.7 to 56.2])., Conclusion: More than half of all patients with suspected stroke do not call EMS directly but call their GP instead. Patients with higher FAST scores, alert outside office hours, and a rapid alert, more often call EMS directly. Patients who call EMS directly are treated with IVT 30 min faster than patients who call the GP first., Trial Registration Number: Netherlands Trial Register: NL7387, (www.trialregister.nl)., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Approximately one-third of patients with ischemic stroke treated with endovascular treatment do not recover to functional independence despite rapid and successful recanalization. We aimed to quantify the importance of predictors of poor functional outcome despite successful reperfusion., Methods: We analyzed patients from the MR CLEAN Registry between March 2014 and November 2017 with successful reperfusion (extended Thrombolysis In Cerebral Infarction ≥2B). First, predictors were selected based on expert opinion and were clustered according to acquisition over time (ie, baseline patient factors, imaging factors, treatment factors, and postprocedural factors). Second, several models were constructed to predict 90-day functional outcome (modified Rankin Scale (mRS)). The relative importance of individual predictors in the most extensive model was expressed by the proportion of unique added χ 2 to the model of that individual predictor., Results: Of 3180 patients, 1913 (60%) had successful reperfusion. Of these 1913 patients, 1046 (55%) were functionally dependent at 90 days (mRS >2). The most important predictors for mRS were baseline patient factors (ie, pre-stroke mRS, added χ 2 0.16; National Institutes of Health Stroke Scale score at baseline, added χ 2 0.12; age, added χ 2 0.10), and postprocedural factors (ie, symptomatic intracranial hemorrhage (sICH), added χ 2 0.12; pneumonia, added χ 2 0.09). The probability of functional independence for a typical stroke patient with sICH was 54% (95% CI 36% to 72%) lower compared with no sICH, and 21% (95% CI 4% to 38%) for pneumonia compared with no pneumonia., Conclusion: Baseline patient factors and postprocedural adverse events are important predictors of poor functional outcome in successfully reperfused patients with ischemic stroke. This implies that prevention of postprocedural adverse events has the greatest potential to further improve outcomes in these patients., Competing Interests: Competing interests: DWJD reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra, Stryker European Operations BV, Medtronic, Thrombolytic Science, and Cerenovus for research, all paid to the institution. AvdL reports funding from the Dutch Heart Foundation, Dutch Brain Foundation, Stryker, Angiocare BV, Medtronic/Covidien/EV3, MEDAC GmbH/LAMEPRO, Penumbra, and Top Medical Concentric, all paid to the institution. CBLMM reports funding from CVON/Dutch Heart Foundation, Stryker, Health Evaluation Netherlands, all paid to the institution, and is a shareholder of Nico.lab, a company that focuses on the use of artificial intelligence for medical imaging analysis. YBWR reports funding from CVON/Dutch Heart Foundation, Stryker, Health Evaluation Netherlands, all paid to the institution, and is a shareholder of Nico.lab, a company that focuses on the use of artificial intelligence for medical imaging analysis., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Thrombus volume in posterior circulation stroke (PCS) has been associated with outcome, through recanalization. Manual thrombus segmentation is impractical for large scale analysis of image characteristics. Hence, in this study we develop the first automatic method for thrombus localization and segmentation on CT in patients with PCS. In this multi-center retrospective study, 187 patients with PCS from the MR CLEAN Registry were included. We developed a convolutional neural network (CNN) that segments thrombi and restricts the volume-of-interest (VOI) to the brainstem (Polar-UNet). Furthermore, we reduced false positive localization by removing small-volume objects, referred to as volume-based removal (VBR). Polar-UNet is benchmarked against a CNN that does not restrict the VOI (BL-UNet). Performance metrics included the intra-class correlation coefficient (ICC) between automated and manually segmented thrombus volumes, the thrombus localization precision and recall, and the Dice coefficient. The majority of the thrombi were localized. Without VBR, Polar-UNet achieved a thrombus localization recall of 0.82, versus 0.78 achieved by BL-UNet. This high recall was accompanied by a low precision of 0.14 and 0.09. VBR improved precision to 0.65 and 0.56 for Polar-UNet and BL-UNet, respectively, with a small reduction in recall to 0.75 and 0.69. The Dice coefficient achieved by Polar-UNet was 0.44, versus 0.38 achieved by BL-UNet with VBR. Both methods achieved ICCs of 0.41 (95% CI: 0.27-0.54). Restricting the VOI to the brainstem improved the thrombus localization precision, recall, and segmentation overlap compared to the benchmark. VBR improved thrombus localization precision but lowered recall.

Background: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes., Methods: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days)., Results: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; P <0.001 and 236 versus 270 minutes; P <0.001, respectively). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 66%; P <0.001). Functional outcome significantly improved (adjusted common odds ratio 1.23 [95% CI, 1.07-1.40]). This effect was attenuated by adjustment for time from onset to reperfusion (adjusted common odds ratio, 1.12 [95% CI, 0.98-1.28]) and successful reperfusion (adjusted common odds ratio, 1.13 [95% CI, 0.99-1.30]). Outcomes were consistent in the analysis per chronological quartile., Conclusions: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates.

Translation of acute ischemic stroke research to the clinical setting remains limited over the last few decades with only one drug, recombinant tissue-type plasminogen activator, successfully completing the path from experimental study to clinical practice. To improve the selection of experimental treatments before testing in clinical studies, the use of large gyrencephalic animal models of acute ischemic stroke has been recommended. Currently, these models include, among others, dogs, swine, sheep, and nonhuman primates that closely emulate aspects of the human setting of brain ischemia and reperfusion. Species-specific characteristics, such as the cerebrovascular architecture or pathophysiology of thrombotic/ischemic processes, significantly influence the suitability of a model to address specific research questions. In this article, we review key characteristics of the main large animal models used in translational studies of acute ischemic stroke, regarding (1) anatomy and physiology of the cerebral vasculature, including brain morphology, coagulation characteristics, and immune function; (2) ischemic stroke modeling, including vessel occlusion approaches, reproducibility of infarct size, procedural complications, and functional outcome assessment; and (3) implementation aspects, including ethics, logistics, and costs. This review specifically aims to facilitate the selection of the appropriate large animal model for studies on acute ischemic stroke, based on specific research questions and large animal model characteristics.

Background: First pass reperfusion (FPR), that is, excellent reperfusion (expanded treatment in cerebral ischemia (eTICI) 2C-3) in one pass, after endovascular treatment (EVT) of an occluded artery in the anterior circulation, is associated with favorable clinical outcome, even when compared with multiple pass excellent reperfusion (MPR). In patients with posterior circulation ischemic stroke (PCS), the same association is expected, but currently unknown. We aimed to assess characteristics associated with FPR and the influence of FPR versus MPR on outcomes in patients with PCS., Methods: We used data from the MR CLEAN Registry, a prospective observational study. The effect of FPR on 24-hour National Institutes of Health Stroke Scale (NIHSS) score, as percentage reduction, and on modified Rankin Scale (mRS) scores at 3 months, was tested with linear and ordinal logistic regression models., Results: Of 224 patients with PCS, 45 patients had FPR, 47 had MPR, and 90 had no excellent reperfusion (eTICI <2C). We did not find an association between any of the patient, imaging, or treatment characteristics and FPR. FPR was associated with better NIHSS (-45% (95% CI: -65% to -12%)) and better mRS scores (adjusted common odds ratio (acOR): 2.16 (95% CI: 1.23 to 3.79)) compared with no FPR. Outcomes after FPR were also more favorable compared with MPR, but the effect was smaller and not statistically significant (NIHSS: -14% (95% CI: -51% to 49%), mRS acOR: 1.50 (95% CI: 0.75 to 3.00))., Conclusions: FPR in patients with PCS is associated with favorable clinical outcome in comparison with no FPR. In comparison with MPR, the effect of FPR was no longer statistically significant. Nevertheless, our data support the notion that FPR should be the treatment target to pursue in every patient treated with EVT., Competing Interests: Competing interests: DWJD reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra Inc., Stryker European Operations BV, Medtronic, Thrombolytic Science, LLC, and Cerenovus for research, all paid to his institution. CBLMM reports grants from CVON/Dutch Heart Foundation, European Commission, TWIN Foundation, Dutch Health Evaluation Program, and Stryker, paid to his institution and is a minority shareholder of NICO.LAB. WHvZ received consultation fees from Stryker and Cerenovus, paid to his institution. PJvD received consultation fees from Stryker, paid to his institution., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Intracranial vessel perforation is a peri-procedural complication during endovascular therapy (EVT). Prompt recognition is important as its occurrence is strongly associated with unfavorable treatment outcomes. However, perforations can be hard to detect because they are rare, can be subtle, and the interventionalist is working under time pressure and focused on treatment of vessel occlusions. Automatic detection holds potential to improve rapid identification of intracranial vessel perforation. In this work, we present the first study on automated perforation detection and localization on X-ray digital subtraction angiography (DSA) image series. We adapt several state-of-the-art single-frame detectors and further propose temporal modules to learn the progressive dynamics of contrast extravasation. Application-tailored loss function and post-processing techniques are designed. We train and validate various automated methods using two national multi-center datasets (i.e., MR CLEAN Registry and MR CLEAN-NoIV Trial), and one international multi-trial dataset (i.e., the HERMES collaboration). With ten-fold cross-validation, the proposed methods achieve an area under the curve (AUC) of the receiver operating characteristic of 0.93 in terms of series level perforation classification. Perforation localization precision and recall reach 0.83 and 0.70 respectively. Furthermore, we demonstrate that the proposed automatic solutions perform at similar level as an expert radiologist., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Charles B.L.M. Majoie received funds from TWIN Foundation (related to this project, paid to institution); and from CVON/Dutch Heart Foundation, Stryker, European Commission, Health Evaluation Netherlands (unrelated; all paid to institution). Charles Majoie is shareholder of Nico.lab, a company that focuses on the use of artificial intelligence for medical imaging analysis. Danny Ruijters is an employee of Philips Healthcare. Wiro J. Niessen is founder, scientific lead, and shareholder of Quantib BV., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke., Methods: We did an open-label, multicentre, randomised controlled trial with a 2 × 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, ≥18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621., Findings: Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1·95 [95% CI 1·13-3·35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1·98 [1·14-3·46]). Both aspirin (adjusted common OR 0·91 [95% CI 0·69-1·21]) and unfractionated heparin (0·81 [0·61-1·08]) led to a non-significant shift towards worse modified Rankin Scale scores., Interpretation: Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome., Funding: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation., Competing Interests: Declaration of interests BR and DWJD report financial support for the current manuscript from the CONTRAST consortium, all paid to their institution. AvdL, BR, HBvdW, CBLMM, DWJD, and MU report funding from the Dutch Heart Foundation, all paid to their institution. AvdL and DWJD report funding from the Dutch Brain foundation paid to their institution. AvdL, BJE, DWJD, and MU report funding from Health Holland Top Sector Life Sciences & Health, all paid to their institution. AvdH, BJE, BR, DWJD, JAV, JMC, and RvdB report grants from the Netherlands Organisation for Health Research and Development, all paid to their institution. AvdL, AJY, HBvdW, CBLMM, and DWJD report funding from Stryker, all paid to their institution. AvdL, AJY, DWJD, and RPHB report funding from Cerenovus, all paid to their institution. AvdL, AJY, DWJD, and JMC report funding from Medtronic, all paid to their institution. AvdL, AJY, and DWJD report funding from Penumbra, all paid to their institution. AvdL and DWJD report funding from Thrombolytic Science paid to their institution. AJY, CBLMM and YBWEMR are minor shareholders of Nicolab. AJY reports funding from Genentech paid to his institution; consulting fees from Penumbra, Cerenovus, Philips, and Vesalio paid to himself; participates in an advisory board of Philips, Nicolab, XCath, and HCA; is part of the endovascular safety monitor of the NIH MOST trial; is an associate editor of the Stroke: Vascular and Interventional Neurology journal; and is a stock owner of Insera. AAP reports institutional grants from Siemens Healthineers and Bayer Healthcare. FJAM reports reimbursements for lectures for Speaker Bureau and Canon Medical Systems. AMT reports being a junior staff member of the Dutch Heart Foundation. BJE reports being a delegate of the Netherlands in the European Union of Medical Specialists Neuroradiology. HBvdW reports grants from the European Union, and participation in an advisory board of Bayer Healthcare and LivaNova, all paid to their institution. CBLMM received funds from the European Commission, TWIN foundation, and Health Evaluation Netherlands, all paid to their institution. JMC reports funding from the Dutch Thrombosis Society and the Dr CJ Vaillant Foundation; consulting fees from Bayer Healthcare, Boehringer, and Portola, all paid to their institution; a fellowship from the European Stroke Organisation; and is a member of the writing committee of the European Stroke Organisation guideline on cerebral venous thrombosis, both unpaid. WvZ reports consulting and speaker fees from Philips, Stryker, Cerenovus, and NicoLab, all paid to their institution; and participation in advisory boards of WeTrust (Philips), Solonda (Anaconda), and InExtremis (CHU Montpellier). All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The aim of this article is to describe neurovascular findings in patients with Loeys Dietz syndrome type III and their possible clinical impact. Loeys Dietz syndrome type III, caused by pathogenic SMAD3 variants, is an autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis. Neurovascular abnormalities have been described in other heritable aortic syndromes, however, reliable data in Loeys Dietz syndrome type III is missing. In our tertiary center, all adult patients with confirmed Loeys Dietz syndrome type III are followed in a standardized aorta outpatient clinic including Computed Tomography Angiography (CTA) of the head and neck region at baseline and (tri) yearly during follow-up. We performed an analysis of the neurovascular imaging findings and clinical follow-up. The primary outcome was a combined endpoint of mortality, dissection, cerebral vascular event and intervention. In addition, tortuosity and vascular growth were assessed. In total 26 patients (mean age 38.4 years, 38.5% males) underwent 102 (mean 3.9 (1-8) per patient) neurovascular Computed Tomography Angiography scans between 2010 and 2021. In 84.6% some form of neurovascular abnormality was found. The abnormalities at baseline were aneurysm (26.9%) dissection flap (7.7%), arterial tortuosity (61.5%), arterial coiling (23.1%) and arterial kinking (3.8%). During follow up (mean 8.85 (1-11) years) one patient suffered from sudden death and one patient needed a neuro-radiological intervention. No cerebral bleeding or stroke occurred. In conclusion, neurovascular imaging in Loeys Dietz syndrome type III patients revealed abnormalities such as aneurysm, tortuosity, coiling and kinking in the vast majority of patients, but clinical events were rare. Neurovascular screening and follow up is advised in all Loeys Dietz syndrome type III patients., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Although the provision of performance feedback to healthcare professionals based on data from quality registries is common practice in many fields of medicine, observational studies of its effect on the quality of care have shown mixed results. The objective of this study is to evaluate the effect of performance feedback on the quality of care for acute ischemic stroke., Methods: PERFEQTOS is a stepped wedge cluster randomized trial in 13 hospitals in the Netherlands providing endovascular thrombectomy for ischemic stroke. The primary outcome is the hospital's door-to-groin time. The study starts with a 6-month period in which none of the hospitals receives the performance feedback intervention. Subsequently, every 6 months, three or four hospitals are randomized to cross over from the control to the intervention conditions, until all hospitals receive the feedback intervention. The feedback intervention consists of a dashboard with quarterly reports on patient characteristics, structure, process, and outcome indicators related to patients with ischemic stroke treated with endovascular thrombectomy. Hospitals can compare their present performance with their own performance in the past and with other hospitals. The performance feedback is provided to local quality improvement teams in each hospital, who define their own targets on specific indicators and develop performance improvement plans. The impact of the performance feedback and improvement plans will be evaluated by comparing the primary outcome before and after the intervention., Discussion: This study will provide evidence on the effectiveness of performance feedback to healthcare providers. The results will be actively disseminated through peer-reviewed journals, conference presentations, and various stakeholder engagement activities., Trial Registration: Netherlands Trial Register NL9090 . Registered on December 3, 2020., (© 2021. The Author(s).)

Introduction: Early detection of large vessel occlusion (LVO) is essential to facilitate fast endovascular treatment. CT angiography (CTA) is used to detect LVO in suspected stroke patients. We aimed to assess the accuracy of CTA evaluations in daily clinical practice in a large cohort of suspected stroke patients., Patients and Methods: We used data from the PRESTO study, a multicenter prospective observational cohort study that included suspected stroke patients between August 2018 and September 2019. Baseline CTAs were re-evaluated by an imaging core laboratory and compared to the local assessment. LVO was defined as an occlusion of the intracranial internal carotid artery, M1 segment, or basilar artery. Medium vessel occlusion (MeVO) was defined as an A1, A2, or M2 occlusion. We calculated the accuracy, sensitivity, and specificity to detect LVO and LVO+MeVO, using the core laboratory evaluation as reference standard., Results: We included 656 patients. The core laboratory detected 89 LVOs and 74 MeVOs in 155 patients. Local observers missed 6 LVOs (7%) and 28 MeVOs (38%), of which 23 M2 occlusions. Accuracy of LVO detection was 99% (95% CI: 98-100%), sensitivity 93% (95% CI: 86-97%), and specificity 100% (95% CI: 99-100%). Accuracy of LVO+MeVO detection was 95% (95% CI: 93-96%), sensitivity 79% (95% CI: 72-85%), and specificity 99% (95% CI: 98-100%)., Discussion and Conclusion: CTA evaluations in daily clinical practice are highly accurate and LVOs are adequately recognized. The detection of MeVOs seems more challenging. The evolving EVT possibilities emphasize the need to improve CTA evaluations in the acute setting., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Diederik Dippel and Aad van der Lugt report funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and unrestricted grants from Penumbra Inc., Stryker, Stryker European Operations BV, Medtronic, Thrombolytic Science, LLC and Cerenovus for research, all paid to institution. Pieter Jan van Doormaal reports funding from Stryker, paid to institution and an unrestricted fee from Bayer. All other authors declare no conflict of interest., (© European Stroke Organisation 2021.)

Background and Purpose: We investigated whether the annual volume of patients with acute ischemic stroke referred from a primary stroke center (PSC) for endovascular treatment (EVT) is associated with treatment times and functional outcome., Methods: We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) registry (2014-2017). We included patients with acute ischemic stroke of the anterior circulation who were transferred from a PSC to a comprehensive stroke center (CSC) for EVT. We examined the association between EVT referral volume of PSCs and treatment times and functional outcome using multivariable regression modeling. The main outcomes were time from arrival at the PSC to groin puncture (PSC-door-to-groin time), adjusted for estimated ambulance travel times, time from arrival at the CSC to groin puncture (CSC-door-to-groin time), and modified Rankin Scale (mRS) score at 90 days after stroke., Results: Of the 3637 patients in the registry, 1541 patients (42%) from 65 PSCs were included. Mean age was 71 years (SD ± 13.3), median National Institutes of Health Stroke Scale score was 16 (interquartile range [IQR]: 12-19), and median time from stroke onset to arrival at the PSC was 53 min (IQR: 38-90). Eighty-three percent had received intravenous thrombolysis. EVT referral volume was not associated with PSC-door-to-groin time (adjusted coefficient: -0.49 min/annual referral, 95% confidence interval [CI]: -1.27 to 0.29), CSC-door-to-groin time (adjusted coefficient: -0.34 min/annual referral, 95% CI: -0.69 to 0.01) or 90-day mRS score (adjusted common odds ratio: 0.99, 95% CI: 0.96-1.01)., Conclusions: In patients transferred from a PSC for EVT, higher PSC volumes do not seem to translate into better workflow metrics or patient outcome., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Randomised controlled trials with perfusion selection have shown benefit of endovascular treatment (EVT) for ischaemic stroke between 6 and 24 hours after symptom onset or time last seen well. However, outcomes after EVT in these late window patients without perfusion imaging are largely unknown. We assessed their characteristics and outcomes in routine clinical practice., Methods: The Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, multicentre study in the Netherlands, included patients with an anterior circulation occlusion who underwent EVT between 2014 and 2017. CT perfusion was no standard imaging modality. We used adjusted ordinal logistic regression analysis to compare patients treated within versus beyond 6.5 hours after propensity score matching on age, prestroke modified Rankin Scale (mRS), National Institutes of Health Stroke Scale, Alberta Stroke Programme Early CT Score (ASPECTS), collateral status, location of occlusion and treatment with intravenous thrombolysis. Outcomes included 3-month mRS score, functional independence (defined as mRS 0-2), and death., Results: Of 3264 patients who underwent EVT, 106 (3.2%) were treated beyond 6.5 hours (median 8.5, IQR 6.9-10.6), of whom 93 (87.7%) had unknown time of stroke onset. CT perfusion was not performed in 87/106 (80.2%) late window patients. Late window patients were younger (mean 67 vs 70 years, p<0.04) and had slightly lower ASPECTS (median 8 vs 9, p<0.01), but better collateral status (collateral score 2-3: 68.3% vs 57.7%, p=0.03). No differences were observed in proportions of functional independence (43.3% vs 40.5%, p=0.57) or death (24.0% vs 28.9%, p=0.28). After matching, outcomes remained similar (adjusted common OR for 1 point improvement in mRS 1.04, 95% CI 0.56 to 1.93)., Conclusions: Without the use of CT perfusion selection criteria, EVT in the 6.5-24-hour time window was not associated with poorer outcome in selected patients with favourable clinical and CT/CT angiography characteristics. randomised controlled trials with lenient inclusion criteria are needed to identify more patients who can benefit from EVT in the late window., Competing Interests: Competing interests: Erasmus MC received funds from Stryker and Bracco Imaging by DWJD. MUMC received funds from Stryker and Codman for consultations by WHvZ. WHvZ and RJvO are principal investigators for the MR CLEAN-LATE trial. R-JBG and FAVP are coordinating researchers for MR CLEAN-LATE. CBLMM received funds from TWIN Foundation (related to this project, paid to institution) and from CVON/Dutch Heart Foundation, Stryker, European Commission, Health Evaluation Netherlands (unrelated; all paid to institution). YBWEMR, CBLMM and IGHJ are shareholders of Nico.lab, a company that focuses on the use of artificial intelligence for medical imaging analysis. RL reports institutional fees from Ischamaview for consultancy. The other authors had no conflicting interests., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations., Methods: We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points., Results: The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P = 0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81)., Conclusions: In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, ISRCTN80619088.)., (Copyright © 2021 Massachusetts Medical Society.)

Background and Purpose: Optimal blood pressure (BP) management in the acute phase of ischemic stroke remains an unresolved issue. It is uncertain whether guidelines for BP management during and after intravenous alteplase can be extrapolated to endovascular treatment (EVT) for stroke due to large artery occlusion in the anterior circulation. We evaluated the associations between systolic BP (SBP) in the first 6 hours following EVT and functional outcome as well as symptomatic intracranial hemorrhage., Methods: Patients of 8 MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry centers, with available data on SBP in the 6 hours following EVT, were analyzed. We evaluated maximum, minimum, and mean SBP. Study outcomes were functional outcome (modified Rankin Scale) at 90 days and symptomatic intracranial hemorrhage. We used multivariable ordinal and binary regression analysis to adjust for important prognostic factors and studied possible effect modification by successful reperfusion., Results: Post-EVT SBP data were available for 1161/1796 patients. Higher maximum SBP (per 10 mm Hg increments) was associated with worse functional outcome (adjusted common odds ratio, 0.93 [95% CI, 0.88–0.98]) and a higher rate of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.17 [95% CI, 1.02–1.36]). The association between minimum SBP and functional outcome was nonlinear with an inflection point at 124 mm Hg. Minimum SBP lower and higher than the inflection point were associated with worse functional outcomes (adjusted common odds ratio, 0.85 per 10 mm Hg decrements [95% CI, 0.76–0.95] and adjusted common odds ratio, 0.81 per 10 mm Hg increments [95% CI, 0.71–0.92]). No association between mean SBP and functional outcome was observed. Successful reperfusion did not modify the relation of SBP with any of the outcomes., Conclusions: Maximum SBP in the first 6 hours following EVT is positively associated with worse functional outcome and an increased risk of symptomatic intracranial hemorrhage. Both lower and higher minimum SBP are associated with worse outcomes. A randomized trial to evaluate whether modifying post-intervention SBP results in better outcomes after EVT for ischemic stroke seems justified.

The growth of unruptured intracranial aneurysms (UIAs) is a strong predictor of rupture. Clinical observations suggest that some UIAs might grow faster after endovascular treatment than untreated UIAs. There are no head-to-head comparisons of incidence rates of UIAs thus far., Methods: We searched PubMed, Embase and Google Scholar for relevant articles from the inception of the databases to March 2020. We pooled and compared the incidence rates for the growth of aneurysms from natural history studies and endovascular treatment studies. Generalized linear models were used for confounder adjustment for the prespecified confounders age, size and location., Results: Twenty-five studies (10 describing growth in natural history and 15 reporting growth after endovascular therapy) considering 6325 aneurysms were included in the meta-analysis. The median size of aneurysms was 3.7 mm in the natural history studies and 6.4 mm in endovascular treatment studies (p = 0.001). The pooled incidence rate (IR) of growth was significantly higher in endovascular treatment studies (IR 52 per 1000 person-years, with a 95% confidence interval (CI) 36-79) compared to natural history studies (IR 28 per 1000 person-years, 95% CI 17 - 46, p-value < 0.01) after adjustment for confounders., Conclusion: Our results suggest that the incidence rate of cerebral aneurysm growth might be higher after endovascular therapy than the incidence rates reported in natural history studies. These results should be viewed in light of the risk of bias of the individual studies and the risk of ecological bias., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The Thrombolysis in Cerebral Infarction (TICI) score is an important metric for reperfusion therapy assessment in acute ischemic stroke. It is commonly used as a technical outcome measure after endovascular treatment (EVT). Existing TICI scores are defined in coarse ordinal grades based on visual inspection, leading to inter- and intra-observer variation. In this work, we present autoTICI, an automatic and quantitative TICI scoring method. First, each digital subtraction angiography (DSA) acquisition is separated into four phases (non-contrast, arterial, parenchymal and venous phase) using a multi-path convolutional neural network (CNN), which exploits spatio-temporal features. The network also incorporates sequence level label dependencies in the form of a state-transition matrix. Next, a minimum intensity map (MINIP) is computed using the motion corrected arterial and parenchymal frames. On the MINIP image, vessel, perfusion and background pixels are segmented. Finally, we quantify the autoTICI score as the ratio of reperfused pixels after EVT. On a routinely acquired multi-center dataset, the proposed autoTICI shows good correlation with the extended TICI (eTICI) reference with an average area under the curve (AUC) score of 0.81. The AUC score is 0.90 with respect to the dichotomized eTICI. In terms of clinical outcome prediction, we demonstrate that autoTICI is overall comparable to eTICI.

Background and Purpose: Mechanical properties of thromboemboli play an important role in the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke. However, very limited data on mechanical properties of human stroke thrombi are available. We aimed to mechanically characterize thrombi retrieved with EVT, and to assess the relationship between thrombus composition and thrombus stiffness., Methods: Forty-one thrombi from 19 patients with acute stroke who underwent EVT between July and October 2019 were mechanically analyzed, directly after EVT. We performed unconfined compression experiments and determined tangent modulus at 75% strain (Et75) as a measure for thrombus stiffness. Thrombi were histologically analyzed for fibrin/platelets, erythrocytes, leukocytes, and platelets, and we assessed the relationship between histological components and Et75 with univariable and multivariable linear mixed regression., Results: Median Et75 was 560 (interquartile range, 393–1161) kPa. In the multivariable analysis, fibrin/platelets were associated with increased Et75 (aβ, 9 [95% CI, 5 to 13]) kPa, erythrocytes were associated with decreased Et75% (aβ, −9 [95% CI, −5 to −13]) kPa. We found no association between leukocytes and Et75. High platelet values were strongly associated with increased Et75 (aβ, 56 [95% CI, 38–73])., Conclusions: Fibrin/platelet content of thrombi retrieved with EVT for acute ischemic stroke is strongly associated with increased thrombus stiffness. For thrombi with high platelet values, there was a very strong relationship with thrombus stiffness. Our data provide a basis for future research on the development of next-generation EVT devices tailored to thrombus composition.

Importance: A carotid web (CW) is a shelf-like lesion along the posterior wall of the internal carotid artery bulb and an underrecognized cause of young stroke. Several studies suggest that patients with symptomatic CW have a high risk of recurrent stroke, but high-quality data are lacking., Objective: To assess the 2-year risk of recurrent stroke in patients with a symptomatic CW., Design, Setting, and Participants: A comparative cohort study used data from the MR CLEAN trial (from 2010-2014) and MR CLEAN Registry (from 2014-2017). Data were analyzed in September 2020. The MR CLEAN trial and MR CLEAN Registry were nationwide prospective multicenter studies on endovascular treatment (EVT) of large vessel occlusion (LVO) stroke in the Netherlands. Baseline data were from 3439 consecutive adult patients with anterior circulation LVO stroke and available computed tomography (CT)-angiography of the carotid bulb. Two neuroradiologists reevaluated CT-angiography images for presence or absence of CW and identified 30 patients with CW ipsilateral to the index stroke. For these 30 eligible CW participants, detailed follow-up data regarding stroke recurrence within 2 years were acquired. These 30 patients with CW ipsilateral to the index stroke were compared with 168 patients without CW who participated in the MR CLEAN extended follow-up trial and who were randomized to the EVT arm., Main Outcomes and Measures: The primary outcome was recurrent stroke occurring within 2 years after the index stroke. Cox proportional hazards regression models were used to compare recurrent stroke rates within 2 years for patients with and without CW, adjusted for age and sex. The research question was formulated prior to data collection., Results: Of 3439 patients with baseline CT-angiography assessed, the median age was 72 years (interquartile range, 61-80 years) and 1813 (53%) were men. Patients with CW were younger (median age, 57 [interquartile range, 46-66] years vs 66 [interquartile range, 56-77] years; P = .02 and more often women (22 of 30 [73%] vs 67 of 168 [40%]; P = .001) than patients without CW. Twenty-eight of 30 patients (93%) received medical management after the index stroke (23 with antiplatelet therapy and 5 with anticoagulant therapy). During 2 years of follow-up, 5 of 30 patients (17%) with CW had a recurrent stroke compared with 5 of 168 patients (3%) without CW (adjusted hazard ratio, 4.9; 95% CI, 1.4-18.1)., Conclusions and Relevance: In this study, 1 of 6 patients with a symptomatic CW had a recurrent stroke within 2 years, suggesting that medical management alone may not provide sufficient protection for patients with CW.

Background: The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied., Methods: We randomly assigned patients within 6 hours after the estimated time of onset of a stroke due to basilar-artery occlusion, in a 1:1 ratio, to receive endovascular therapy or standard medical care. The primary outcome was a favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) at 90 days. The primary safety outcomes were symptomatic intracranial hemorrhage within 3 days after the initiation of treatment and mortality at 90 days., Results: A total of 300 patients were enrolled (154 in the endovascular therapy group and 146 in the medical care group). Intravenous thrombolysis was used in 78.6% of the patients in the endovascular group and in 79.5% of those in the medical group. Endovascular treatment was initiated at a median of 4.4 hours after stroke onset. A favorable functional outcome occurred in 68 of 154 patients (44.2%) in the endovascular group and 55 of 146 patients (37.7%) in the medical care group (risk ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.50). Symptomatic intracranial hemorrhage occurred in 4.5% of the patients after endovascular therapy and in 0.7% of those after medical therapy (risk ratio, 6.9; 95% CI, 0.9 to 53.0); mortality at 90 days was 38.3% and 43.2%, respectively (risk ratio, 0.87; 95% CI, 0.68 to 1.12)., Conclusions: Among patients with stroke from basilar-artery occlusion, endovascular therapy and medical therapy did not differ significantly with respect to a favorable functional outcome, but, as reflected by the wide confidence interval for the primary outcome, the results of this trial may not exclude a substantial benefit of endovascular therapy. Larger trials are needed to determine the efficacy and safety of endovascular therapy for basilar-artery occlusion. (Funded by the Dutch Heart Foundation and others; BASICS ClinicalTrials.gov number, NCT01717755; Netherlands Trial Register number, NL2500.)., (Copyright © 2021 Massachusetts Medical Society.)

Background First-pass reperfusion (FPR) is associated with favorable outcome after endovascular treatment. It is unknown whether this effect is independent of patient characteristics and whether FPR has better outcomes compared with excellent reperfusion (Expanded Thrombolysis in Cerebral Infarction [eTICI] 2C-3) after multiple-passes reperfusion. We aimed to evaluate the association between FPR and outcome with adjustment for patient, imaging, and treatment characteristics to single out the contribution of FPR. Methods and Results FPR was defined as eTICI 2C-3 after 1 pass. Multivariable regression models were used to investigate characteristics associated with FPR and to investigate the effect of FPR on outcomes. We included 2686 patients of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. Factors associated with FPR were as follows: history of hyperlipidemia (adjusted odds ratio [OR], 1.05; 95% CI, 1.01-1.10), middle cerebral artery versus intracranial carotid artery occlusion (adjusted OR, 1.11; 95% CI, 1.06-1.16), and aspiration versus stent thrombectomy (adjusted OR, 1.07; 95% CI, 1.03-1.11). Interventionist experience increased the likelihood of FPR (adjusted OR, 1.03 per 50 patients previously treated; 95% CI, 1.01-1.06). Adjusted for patient, imaging, and treatment characteristics, FPR remained associated with a better 24-hour National Institutes of Health Stroke Scale (NIHSS) score (-37%; 95% CI, -43% to -31%) and a better modified Rankin Scale (mRS) score at 3 months (adjusted common OR, 2.16; 95% CI, 1.83-2.54) compared with no FPR (multiple-passes reperfusion+no excellent reperfusion), and compared with multiple-passes reperfusion alone (24-hour NIHSS score, (-23%; 95% CI, -31% to -14%), and mRS score (adjusted common OR, 1.45; 95% CI, 1.19-1.78)). Conclusions FPR compared with multiple-passes reperfusion is associated with favorable outcome, independently of patient, imaging, and treatment characteristics. Factors associated with FPR were the experience of the interventionist, history of hyperlipidemia, location of occluded artery, and use of an aspiration device compared with stent thrombectomy.