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Background: The ratio of intracranial cerebrospinal fluid (CSF) volume to intracranial volume (ICV) has been identified as a potential predictor of malignant edema formation in patients with acute ischemic stroke. Aims: We aimed to evaluate the added value of the CSF/ICV ratio in a model to predict malignant edema formation in patients who underwent endovascular treatment. Methods: We included patients from the MR CLEAN Registry, a prospective national multicenter registry of patients who were treated with endovascular treatment between 2014 and 2017 because of acute ischemic stroke caused by large vessel occlusion. The CSF/ICV ratio was automatically measured on baseline thin-slice noncontrast CT. The primary outcome was the occurrence of malignant edema based on clinical and imaging features. The basic model included the following predictors: age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT score, occlusion of the internal carotid artery, collateral score, time between symptom onset and groin puncture, and unsuccessful reperfusion. The extended model included the basic model and the CSF/ICV ratio. The performance of the basic and the extended model was compared with the likelihood ratio test. Results: Malignant edema occurred in 40 (6%) of 683 patients. In the extended model, a lower CSF/ICV ratio was associated with the occurrence of malignant edema (odds ratio (OR) per percentage point, 1.2; 95% confidence interval (CI) 1.1–1.3, p Conclusions: Adding the CSF/ICV ratio improves a multimodal prediction model for the occurrence of malignant edema after endovascular treatment.

Background and ObjectivesTo explore clinical and safety outcomes of patients with acute ischemic stroke (AIS) and active cancer after endovascular treatment (EVT).MethodsUsing data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry, we compared patients with active cancer (defined as cancer diagnosed within 12 months before stroke, metastatic disease, or current cancer treatment) to patients without cancer. Outcomes were 90-day modified Rankin Scale (mRS) score, mortality, successful reperfusion (expanded Treatment in Cerebral Infarction score ≥2b), symptomatic intracranial hemorrhage (sICH), and recurrent stroke. Subgroup analyses were performed in patients with a prestroke mRS score of 0 or 1 and according to treatment setting (curative or palliative). Analyses were adjusted for prognostic variables.ResultsOf 2,583 patients who underwent EVT, 124 (4.8%) had active cancer. They more often had prestroke disability (mRS score ≥2: 34.1% vs 16.6%). The treatment setting was palliative in 25.3% of the patients. There was a shift toward worse functional outcome at 90 days in patients with active cancer (adjusted common odds ratio [acOR] 2.2, 95% confidence interval [CI] 1.5–3.2). At 90 days, patients with active cancer were less often independent (mRS score 0–2: 22.6% vs 42.0%, adjusted OR [aOR] 0.5, 95% CI 0.3–0.8) and more often dead (52.2% vs 26.5%, aOR 3.2, 95% CI 2.1–4.9). Successful reperfusion (67.8% vs 60.5%, aOR 1.4, 95% CI 1.0–2.1) and sICH rates (6.5% vs 5.9%, aOR 1.1, 95% CI 0.5–2.3) did not differ. Recurrent stroke within 90 days was more common in patients with active cancer (4.0% vs 1.3%, aOR 3.1, 95% CI 1.2–8.1). The sensitivity analysis of patients with a prestroke mRS score of 0 or 1 showed that patients with active cancer still had a worse outcome at 90 days (acOR 1.9, 95% CI 1.2–3.0). Patients with active cancer in a palliative treatment setting regained functional independence less often compared to patients in a curative setting (18.2% vs 32.1%), and mortality was higher (81.8% vs 39.3%).DiscussionDespite similar technical success, patients with active cancer had significantly worse outcomes after EVT for AIS. Moreover, they had an increased risk of recurrent stroke. Nevertheless, about a quarter of the patients regained functional independence, and the risk of other complications, most notably sICH, was not increased.Classification of EvidenceThis study provides Class I evidence that patients with active cancer undergoing EVT for AIS have worse functional outcomes at 90 days compared to those without active cancer.

BackgroundClinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS.MethodsA literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included.ResultsWe screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT.ConclusionStudies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT.

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.

Background and Purpose: Acute ischemic stroke due to large vessel occlusion is uncommon in young adults. We assessed stroke cause in young patients and compared their outcomes after endovascular thrombectomy with older patients. Methods: We used data (March 2014 until November 2017) of patients with an anterior circulation large vessel occlusion stroke from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a nationwide, prospective study on endovascular thrombectomy in the Netherlands. We compared young patients (18–49 years) with older patients (≥50 years). Outcomes included modified Rankin Scale score after 90 days (both shift and dichotomized analyses), expanded Thrombolysis in Cerebral Infarction score, and symptomatic intracranial hemorrhage. Analyses were adjusted for confounding. Results: We included 3256 patients, 310 (10%) were 18 to 49 years old. Young patients had lower median National Institutes of Health Stroke Scale scores (14 versus 16, P Conclusions: Ten percent of patients with acute ischemic stroke undergoing endovascular thrombectomy were younger than 50. Cardioembolism and carotid dissection were common underlying causes in young patients. In one-third of cases, no cause was identified, indicating the need for more research on stroke cause in young patients. Young patients had better prognosis and lower risk of symptomatic intracranial hemorrhage than older patients.

Background and Purpose— Hemorrhagic transformation (HT) after acute ischemic stroke may cause severe neurological deterioration and affects functional outcome. Identifying patients most likely to suffer from this complication could potentially be used for future treatment selection. Reperfusion after endovascular therapy could be associated with different risk factors for HT than intravenous thrombolytics as these treatments largely differ. In this study, we aimed to identify clinical and imaging markers that are associated with HT subtypes in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) population. Methods— In this post hoc analysis, all patients with follow-up imaging were included. HT was classified according to ECASS II (European Cooperative Acute Stroke Study). Variables with an association of P Results— Of the 478 out of 500 included patients in this subanalysis, 46% had HT (n=222). Of these, 66% had hemorrhagic infarction (n=147) and 34% PH (n=75). Symptomatic intracranial hemorrhage was observed in 7.3% (n=35) of all patients. Baseline National Institutes of Health Stroke Scale (odds ratio [OR], 1.05,95% CI, 1.01–1.09 per point) and absent/poor collaterals (OR, 1.90; 95% CI, 1.05–3.42) were significantly associated with hemorrhagic infarction. Increased systolic blood pressure (OR, 1.17; 95% CI, 1.05–1.31 per 10 mm Hg) and atrial fibrillation (OR, 1.94; 95% CI, 1.08–3.48) were associated with PH. Increased systolic blood pressure (OR, 1.28; 95% CI, 1.12–1.48) and antiplatelet use (OR, 2.6; 95% CI, 1.08–6.3) were associated with symptomatic intracranial hemorrhage. Conclusions— Clinical and imaging stroke severity parameters were associated with HT, both in hemorrhagic infarction and PH, whereas baseline patients characteristics like systolic blood pressure, atrial fibrillation, and antiplatelet use were only associated with PH or symptomatic intracranial hemorrhage. Clinical Trial Registration— URL: http://www.controlled-trials.com . Unique identifier: ISRCTN10888758.

Background Early prediction of malignant infarction may guide treatment decisions. For patients who received endovascular treatment, the risk of malignant infarction is unknown and risk factors are unrevealed. Aims The objective of this study is to estimate the incidence of malignant infarction after endovascular treatment in patients with an occlusion of the anterior circulation, to identify independent risk factors, and to establish a model for prediction. Methods We analyzed patients who received endovascular treatment for a large vessel occlusion in the anterior circulation within 6.5 h after symptom onset, included in the Dutch MR CLEAN Registry between March 2014 and June 2016. We compared patients with and without malignant infarction. Candidate predictors were incorporated in a multivariable binary logistic regression model. The final prediction model was established using backward elimination. Discrimination and calibration were evaluated with the area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow test. Results Of 1445 patients, 82 (6%) developed malignant infarction. Independent predictors were lower age, higher National Institutes of Health Stroke Scale (NIHSS), lower alberta stroke program early CT score (ASPECTS), internal carotid artery occlusion, lower collateral score, longer times from onset to groin puncture, and unsuccessful reperfusion. The AUROC of a prediction model combining these features was 0.83 (95% confidence interval (CI): 0.79–0.88) and the Hosmer-Lemeshow test indicated appropriate calibration (P = 0.937). Conclusion The risk of malignant infarction after endovascular treatment started within 6.5 h of stroke onset is approximately 6%. Successful reperfusion decreases the risk. A prediction model combining easily retrievable measures of age, ASPECTS, collateral status, and reperfusion shows good discrimination between patients who will develop malignant infarction and those who will not.

Background Endovascular therapy (EVT) for acute ischemic stroke due to proximal occlusion of the anterior intracranial circulation, started within 6 h from symptom onset, has been proven safe and effective. Recently, EVT has been proven effective beyond the 6-h time window in a highly selected population using CT perfusion or MR diffusion. Unfortunately, these imaging modalities are not available in every hospital, and strict selection criteria might exclude patients who could still benefit from EVT. The presence of collaterals on CT angiography (CTA) may offer a more pragmatic imaging criterion that predicts possible benefit from EVT beyond 6 h from time last known well. The aim of this study is to assess the safety and efficacy of EVT for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow. Methods The MR CLEAN-LATE trial is a multicenter, randomized, open-label, blinded endpoint trial, aiming to enroll 500 patients. We will investigate the efficacy of EVT between 6 and 24 h from time last known well in acute ischemic stroke due to a proximal intracranial anterior circulation occlusion confirmed by CTA or MRA. Patients with any collateral flow (poor, moderate, or good collaterals) on CTA will be included. The inclusion of poor collateral status will be restricted to a maximum of 100 patients. In line with the current Dutch guidelines, patients who fulfill the characteristics of included patients in DAWN and DEFUSE 3 will be excluded as they are eligible for EVT as standard care. The primary endpoint is functional outcome at 90 days, assessed with the modified Rankin Scale (mRS) score. Treatment effect will be estimated with ordinal logistic regression (shift analysis) on the mRS at 90 days. Secondary endpoints include clinical stroke severity at 24 h and 5–7 days assessed by the NIHSS, symptomatic intracranial hemorrhage, recanalization at 24 h, follow-up infarct size, and mortality at 90 days, Discussion This study will provide insight into whether EVT is safe and effective for patients treated between 6 and 24 h from time last known well after selection based on the presence of collateral flow on CTA. Trial registration NL58246.078.17, ISRCTN19922220, Registered on 11 December 2017

BackgroundEndovascular treatment (EVT) has greatly improved the prognosis of acute ischemic stroke (AIS) patients with a proximal intracranial large vessel occlusion (LVO) of the anterior circulation. Currently, there is clinical equipoise concerning the added benefit of intravenous alteplase administration (IVT) prior to EVT. The aim of this study is to assess the efficacy and safety of omitting IVT before EVT in patients with AIS caused by an anterior circulation LVO.MethodsMR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients ≥ 18 years of age with a pre-stroke mRS DiscussionIVT prior to EVT might facilitate early reperfusion before EVT or improved reperfusion rates during EVT. Conversely, among other potential adverse effects, the increased risk of bleeding could nullify the beneficial effects of IVT. MR CLEAN-NO IV will provide insight into whether IVT is still of added value in patients eligible for EVT.Trial registrationwww.isrctn.com:ISRCTN80619088. Registered on 31 October 2017.

Background: Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not recover even after complete recanalization. To some extent, this may be attributable to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet agents and heparin. It is unknown whether periprocedural antithrombotic medication in patients treated with EVT improves functional outcome. The aim of this study is to assess the effect of acetylsalicylic acid (ASA) and unfractionated heparin (UFH), alone, or in combination, given to patients with an ischemic stroke caused by an intracranial large vessel occlusion in the anterior circulation during EVT.Methods: MR CLEAN-MED is a multicenter phase III trial with a prospective, 2 x 3 factorial randomized, open label, blinded end-point (PROBE) design, which aims to enroll 1500 patients. The trial is designed to evaluate the effect of intravenous ASA (300 mg), UFH (low or moderate dose), both or neither as adjunctive therapy to EVT. We enroll adult patients with a clinical diagnosis of stroke (NIHSS >= 2) and with a confirmed intracranial large vessel occlusion in the anterior circulation on CTA or MRA, when EVT within 6 h from symptom onset is indicated and possible. The primary outcome is the score on the modified Rankin Scale (mRS) at 90 days. Treatment effect on the mRS will be estimated with ordinal logistic regression analysis, with adjustment for main prognostic variables. Secondary outcomes include stroke severity measured with the NIHSS at 24 h and at 5-7 days, follow-up infarct volume, symptomatic intracranial hemorrhage (sICH), and mortality.Discussion: Clinical equipoise exists whether antithrombotic medication should be administered during EVT for a large vessel occlusion, as ASA and/or UFH may improve functional outcome, but might also lead to an increased risk of sICH. When one or both of the study treatments show the anticipated effect on outcome, we will be able to improve outcome of patients treated with EVT by 5%. This amounts to more than 50 patients annually in the Netherlands, more than 1800 in Europe, and more than 1300 in the USA.

Supplemental Digital Content is available in the text., Background and Purpose— Due to chronic hypoperfusion, cervical atherosclerosis may promote cerebral collateral circulation. We hypothesized that patients with ischemic stroke due to cervical carotid atherosclerosis have a more extensive collateral circulation and better outcomes than patients with cardioembolism. We tested this hypothesis in a population of patients who underwent endovascular treatment for large vessel occlusion. Methods— From the MR-CLEAN Registry (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), we selected consecutive adult endovascular treatment patients (March 2014 to June 2016) with acute ischemic stroke due to anterior circulation large vessel occlusion and compared patients with cervical carotid artery stenosis >50% to those with cardioembolic etiology. The primary outcome was collateral score, graded on a 4-point scale. Secondary outcomes included the modified Rankin Scale (mRS) score and mortality at 90 days. We performed multivariable regression analyses and adjusted for potential confounders. Results— Of 1627 patients in the Registry, 190 patients with cervical carotid atherosclerosis and 476 with cardioembolism were included. Patients with cervical carotid atherosclerosis were younger (median 69 versus 76 years, P

Supplemental Digital Content is available in the text., Background and Purpose— The location of the thrombus as observed on first digital subtraction angiography during endovascular treatment may differ from the initial observation on initial noninvasive imaging. We studied the incidence of thrombus dynamics, its impact on patient outcomes, and its association with intravenous thrombolytics. Methods— We included patients from the MR CLEAN registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke) with an initial target occlusion on computed tomography angiography located in the intracranial internal carotid artery, M1, or M2. The conventional angiography target occlusion was defined during endovascular treatment. Thrombus dynamics were classified as growth, stability, migration, and resolution. The primary outcome was functional outcome at 90 days (modified Rankin Scale). The secondary outcomes were successful and complete reperfusion (extended treatment in cerebral infarction scores of 2b-3 and 3, respectively). Results— The analysis included 1349 patients. Thrombus migration occurred in 302 (22%) patients, thrombus growth in 87 (6%), and thrombus resolution in 39 (3%). Intravenous treatment with alteplase was associated with more thrombus migration (adjusted odds ratio, 2.01; CI, 1.29–3.11) and thrombus resolution (adjusted odds ratio, 1.85; CI, 1.22–2.80). Thrombus migration was associated with a lower chance of complete reperfusion (adjusted odds ratio, 0.57; CI, 0.42–0.78) and successful reperfusion (adjusted odds ratio, 0.74; CI, 0.55–0.99). In the subgroup of patients with M1 initial target occlusion, thrombus migration was associated with better functional outcome (adjusted common odds ratio, 1.49; CI, 1.02–2.17), and there was a trend towards better functional outcome in patients with thrombus resolution (adjusted common odds ratio, 2.23; CI, 0.93–5.37). Conclusions— In patients with acute ischemic stroke, thrombus location regularly changes between computed tomography angiography and digital subtraction angiography. Administration of intravenous alteplase increases the chance of thrombus migration and resolution. Thrombus migration is associated with better functional outcome but reduces the rate of complete reperfusion.

Background and Purpose— Endovascular treatment (EVT) of patients with acute ischemic stroke because of large vessel occlusion involves complicated logistics, which may cause a delay in treatment initiation during off-hours. This might lead to a worse functional outcome. We compared workflow intervals between endovascular treatment–treated patients presenting during off- and on-hours. Methods— We retrospectively analyzed data from the MR CLEAN Registry, a prospective, multicenter, observational study in the Netherlands and included patients with an anterior circulation large vessel occlusion who presented between March 2014 and June 2016. Off-hours were defined as presentation on Monday to Friday between 17:00 and 08:00 hours, weekends (Friday 17:00 to Monday 8:00) and national holidays. Primary end point was first door to groin time. Secondary end points were functional outcome at 90 days (modified Rankin Scale) and workflow time intervals. We stratified for transfer status, adjusted for prognostic factors, and used linear and ordinal regression models. Results— We included 1488 patients of which 936 (62.9%) presented during off-hours. Median first door to groin time was 140 minutes (95% CI, 110–182) during off-hours and 121 minutes (95% CI, 85–157) during on-hours. Adjusted first door to groin time was 14.6 minutes (95% CI, 9.3–20.0) longer during off-hours. Door to needle times for intravenous therapy were slightly longer (3.5 minutes, 95% CI, 0.7–6.3) during off-hours. Groin puncture to reperfusion times did not differ between groups. For transferred patients, the delay within the intervention center was 5.0 minutes (95% CI, 0.5–9.6) longer. There was no significant difference in functional outcome between patients presenting during off- and on-hours (adjusted odds ratio, 0.92; 95% CI, 0.74–1.14). Reperfusion rates and complication rates were similar. Conclusions— Presentation during off-hours is associated with a slight delay in start of endovascular treatment in patients with acute ischemic stroke. This treatment delay did not translate into worse functional outcome or increased complication rates.

BackgroundCollateral status modified the effect of endovascular treatment (EVT) for stroke in several randomized trials. We assessed the association between collaterals and functional outcome in EVT treated patients and investigated if this association is time dependent.MethodsWe included consecutive patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN) Registry (March 2014–June 2016) with an anterior circulation large vessel occlusion undergoing EVT. Functional outcome was measured on the modified Rankin Scale (mRS) at 90 days. We investigated the association between collaterals and mRS in the MR CLEAN Registry with ordinal logistic regression and if this association was time dependent with an interaction term. Additionally, we determined modification of EVT effect by collaterals compared with MR CLEAN controls, and also investigated if this was time dependent with multiplicative interaction terms.Results1412 patients were analyzed. Functional independence (mRS score of 0–2) was achieved in 13% of patients with grade 0 collaterals, in 27% with grade 1, in 46% with grade 2, and in 53% with grade 3. Collaterals were significantly associated with mRS (adjusted common OR 1.5 (95% CI 1.4 to 1.7)) and significantly modified EVT benefit (P=0.04). None of the effects were time dependent. Better collaterals corresponded to lower mortality (PConclusionIn routine clinical practice, better collateral status is associated with better functional outcome and greater treatment benefit in EVT treated acute ischemic stroke patients, independent of time to treatment. Within the 6 hour time window, a substantial proportion of patients with absent and poor collaterals can still achieve functional independence.

Background It is unclear whether intravenous thrombolysis ( IVT ) with alteplase before endovascular treatment ( EVT ) is beneficial for patients with acute ischemic stroke caused by a large vessel occlusion. We compared clinical and procedural outcomes, safety, and workflow between patients treated with both IVT and EVT and those treated with EVT alone in routine clinical practice. Methods and Results Using multivariable regression, we evaluated the association of IVT + EVT with 90‐day functional outcome (modified Rankin Scale), mortality, reperfusion, first‐pass effect, and symptomatic intracranial hemorrhage in the MR CLEAN (Multicenter Randomised Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) Registry. Of 1485 patients, 1161 (78%) were treated with IVT + EVT , and 324 (22%) with EVT alone. Patients treated with IVT + EVT had atrial fibrillation less often (16% versus 44%) and had better pre‐stroke modified Rankin Scale scores (pre‐stroke modified Rankin Scale 0: 73% versus 52%) than those treated with EVT alone. Procedure time was shorter in the IVT + EVT group (median 62 versus 68 minutes). Nontransferred IVT + EVT patients had longer door‐to‐groin‐puncture times (median 105 versus 94 minutes). IVT + EVT was associated with better functional outcome (adjusted common odds ratio 1.47; 95% CI : 1.10–1.96) and lower mortality (adjusted odds ratio 0.58; 95% CI : 0.40–0.82). Successful reperfusion, first‐pass effect, and symptomatic intracranial hemorrhage did not differ between groups. Conclusions In this observational study, patients treated with IVT + EVT had better clinical outcomes than patients who received EVT alone. This finding may demonstrate a true benefit of IVT before EVT , but its interpretation is hampered by the possibility of residual confounding and selection bias. Randomized trials are required to properly assess the effect of IVT before EVT .

Supplemental Digital Content is available in the text., Background and Purpose— To assess the effect of inter-hospital transfer on time to treatment and functional outcome after endovascular treatment (EVT) for acute ischemic stroke, we compared patients transferred from a primary stroke center to patients directly admitted to an intervention center in a large nationwide registry. Methods— MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry is an ongoing, prospective, observational study in all centers that perform EVT in the Netherlands. We included adult patients with an acute anterior circulation stroke who received EVT between March 2014 to June 2016. Primary outcome was time from arrival at the first hospital to arterial groin puncture. Secondary outcomes included the 90-day modified Rankin Scale score and functional independence (modified Rankin Scale score of 0–2). Results— In total 821/1526 patients, (54%) were transferred from a primary stroke center. Transferred patients less often had prestroke disability (227/800 [28%] versus 255/699 [36%]; P=0.02) and more often received intravenous thrombolytics (659/819 [81%] versus 511/704 [73%]; P

Goal: Insufficient data is available about safety and efficacy of endovascular treatment (EVT) in patients with minor stroke symptoms because these patients were excluded from most randomized trials. We aimed to compare characteristics, functional outcome, and complications in patients with minor ischemic stroke National Institutes of Health Stroke Scale score ≤5 (NIHSS score ≤5) and moderate to severe ischemic stroke (NIHSS score ≥6) due to intracranial proximal artery occlusion of the anterior circulation who underwent EVT. Materials and Methods: We report patients with an anterior circulation occlusion who were included between March 2014 and June 2016 in the multicenter randomized clinical trial of EVT of acute ischemic stroke in the Netherlands Registry, a prospective, multicenter, observational study for stroke centers that perform EVT in the Netherlands. Minor ischemic stroke was defined as baseline NIHSS score of 5 or less. Primary outcome is the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes include symptomatic intracranial hemorrhage (sICH) and mortality. Findings: Seventy-one (5.5%) patients had a NIHSS score of 5 or less. Functional independence (mRS 0-2 at 90 days) was reached in 75% of these patients, compared to 40% of patients with NIHSS score of 6 or more. sICH occurred in 4% of patients, of which 1% occurred peri-interventionally. Death occurred in 6% of patients. Conclusions: Patients with minor ischemic stroke with an intracranial proximal arterial occlusion of the anterior circulation who underwent EVT have a high chance of favorable outcome and appear to have low occurrence of treatment-related sICH. Therefore, our results encourage the use of EVT for minor ischemic stroke in the absence of effect estimates from controlled studies.