Manon Kappelhof | University of Amsterdam (original) (raw)

Papers by Manon Kappelhof

Research paper thumbnail of Endovascular treatment effect diminishes with increasing thrombus perviousness: data from 7 acute ischaemic stroke trials

Stroke, 2021

BACKGROUND AND PURPOSE: Thrombus perviousness estimates residual flow along a thrombus in acute i... more BACKGROUND AND PURPOSE: Thrombus perviousness estimates residual flow along a thrombus in acute ischemic stroke, based on radiological images, and may influence the benefit of endovascular treatment for acute ischemic stroke. We aimed to investigate potential endovascular treatment (EVT) effect modification by thrombus perviousness. METHODS: We included 443 patients with thin-slice imaging available, out of 1766 patients from the pooled HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set of 7 randomized trials on EVT in the early window (most within 8 hours). Control arm patients (n=233) received intravenous alteplase if eligible (212/233; 91%). Intervention arm patients (n=210) received additional EVT (prior alteplase in 178/210; 85%). Perviousness was quantified by thrombus attenuation increase on admission computed tomography angiography compared with noncontrast computed tomography. Multivariable regression analyses were performed including multiplicative interaction terms between thrombus attenuation increase and treatment allocation. In case of significant interaction, subgroup analyses by treatment arm were performed. Our primary outcome was 90-day functional outcome (modified Rankin Scale score), resulting in an adjusted common odds ratio for a one-step shift towards improved outcome. Secondary outcomes were mortality, successful reperfusion (extended Thrombolysis in Cerebral Infarction score, 2B-3), and follow-up infarct volume (in mL). RESULTS: Increased perviousness was associated with improved functional outcome. After adding a multiplicative term of thrombus attenuation increase and treatment allocation, model fit improved significantly (P=0.03), indicating interaction between perviousness and EVT benefit. Control arm patients showed significantly better outcomes with increased perviousness (adjusted common odds ratio, 1.2 [95% CI, 1.1-1.3]). In the EVT arm, no significant association was found (adjusted common odds ratio, 1.0 [95% CI, 0.9-1.1]), and perviousness was not significantly associated with successful reperfusion. Follow-up infarct volume (12% [95% CI, 7.0-17] per 5 Hounsfield units) and chance of mortality (adjusted odds ratio, 0.83 [95% CI, 0.70-0.97]) decreased with higher thrombus attenuation increase in the overall population, without significant treatment interaction. CONCLUSIONS: Our study suggests that the benefit of best medical care including alteplase, compared with additional EVT, increases in patients with more pervious thrombi.

Research paper thumbnail of Bifurcation occlusions and endovascular treatment outcome in acute ischemic stroke

Journal of NeuroInterventional Surgery

BackgroundA thrombus in the M1 segment of the middle cerebral artery (MCA) can occlude this main ... more BackgroundA thrombus in the M1 segment of the middle cerebral artery (MCA) can occlude this main stem only or extend into the M1-M2 bifurcation. The occlusion pattern may affect endovascular treatment (EVT) success, as a bifurcated thrombus may be more prone to fragmentation during retrieval.ObjectiveTo investigate whether bifurcated thrombus patterns are associated with EVT procedural and clinical outcomes.MethodsOcclusion patterns of MCA thrombi on CT angiography from MR CLEAN Registry patients were classified into three groups: main stem occlusion, bifurcation occlusion extending into one M2 branch, and bifurcation occlusion extending into both M2 branches. Procedural parameters, procedural outcomes (reperfusion grade and embolization to new territory), and clinical outcomes (24-48 hour National Institutes of Health Stroke Scale [NIHSSFU] score, change in NIHSS scores between 24 and 48 hours and baseline ∆[NIHSS], and 90-day modified Rankin Scale [mRS] scores) were compared betwe...

Research paper thumbnail of Fully Automated Thrombus Segmentation on CT Images of Patients with Acute Ischemic Stroke

Diagnostics

Thrombus imaging characteristics are associated with treatment success and functional outcomes in... more Thrombus imaging characteristics are associated with treatment success and functional outcomes in stroke patients. However, assessing these characteristics based on manual annotations is labor intensive and subject to observer bias. Therefore, we aimed to create an automated pipeline for consistent and fast full thrombus segmentation. We used multi-center, multi-scanner datasets of anterior circulation stroke patients with baseline NCCT and CTA for training (n = 228) and testing (n = 100). We first found the occlusion location using StrokeViewer LVO and created a bounding box around it. Subsequently, we trained dual modality U-Net based convolutional neural networks (CNNs) to segment the thrombus inside this bounding box. We experimented with: (1) U-Net with two input channels for NCCT and CTA, and U-Nets with two encoders where (2) concatenate, (3) add, and (4) weighted-sum operators were used for feature fusion. Furthermore, we proposed a dynamic bounding box algorithm to adjust t...

Research paper thumbnail of WSO909632 Supplemental Material2 - Supplemental material for qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients

Supplemental material, WSO909632 Supplemental Material2 for qTICI: Quantitative assessment of bra... more Supplemental material, WSO909632 Supplemental Material2 for qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients by Haryadi Prasetya, Lucas A Ramos, Thabiso Epema, Kilian M Treurniet, Bart J Emmer, Ido R van den Wijngaard, Guang Zhang, Manon Kappelhof, Olvert A Berkhemer, Albert J Yoo, Yvo BEWM Roos, Robert J van Oostenbrugge, Diederik WJ Dippel, Wim H van Zwam, Aad van der Lugt, Bas AJM de Mol, Charles BLM Majoie, Ed van Bavel, Henk A Marquering and on behalf of the MR CLEAN Registry Investigators in International Journal of Stroke

Research paper thumbnail of WSO909632 Supplemental Material1 - Supplemental material for qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients

Supplemental material, WSO909632 Supplemental Material1 for qTICI: Quantitative assessment of bra... more Supplemental material, WSO909632 Supplemental Material1 for qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients by Haryadi Prasetya, Lucas A Ramos, Thabiso Epema, Kilian M Treurniet, Bart J Emmer, Ido R van den Wijngaard, Guang Zhang, Manon Kappelhof, Olvert A Berkhemer, Albert J Yoo, Yvo BEWM Roos, Robert J van Oostenbrugge, Diederik WJ Dippel, Wim H van Zwam, Aad van der Lugt, Bas AJM de Mol, Charles BLM Majoie, Ed van Bavel, Henk A Marquering and on behalf of the MR CLEAN Registry Investigators in International Journal of Stroke

Research paper thumbnail of Improvements in Endovascular Treatment for Acute Ischemic Stroke: A Longitudinal Study in the MR CLEAN Registry

Stroke

Background: We evaluated data from all patients in the Netherlands who underwent endovascular tre... more 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 p...

Research paper thumbnail of Abstract 75: Hemorrhagic Transformation After Acute Ischemic Stroke Due to a Large Vessel Occlusion is Associated With Less Treatment Benefit

Stroke

Introduction: Intracranial hemorrhage after acute ischemic stroke patients manifests as natural p... more Introduction: Intracranial hemorrhage after acute ischemic stroke patients manifests as natural progression or as a complication of treatment with potential subsequent neurological deterioration. Currently it is unclear whether these hemorrhagic transformations (HT) contribute to the poorer functional outcomes observed in patients with large infarcts. The purpose of this study is to assess the association of HT with follow-up infarct volume (FIV) and functional outcome at 90 days after AIS. Additionally, we determined whether the development of HT was associated with a diminished endovascular therapy (EVT) effect. Methods: All patients from the HERMES collaboration with follow-up imaging were included. HERMES is pooled data from seven randomized controlled trials that assessed the efficacy and safety of EVT compared to usual care. Patients with HT were identified according to the ECASS classification and FIV was assessed on CT or MRI. Infarct and hemorrhage were included in the FIV....

Research paper thumbnail of Successful reperfusion in relation to the number of passes: comparing outcomes of first pass expanded Treatment In Cerebral Ischemia (eTICI) 2B with multiple-pass eTICI 3

Journal of NeuroInterventional Surgery

BackgroundHigher expanded Treatment In Cerebral Ischemia (eTICI) reperfusion scores after endovas... more BackgroundHigher 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.MethodsWe 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.ResultsWe included 699 patients: 178 patients with single-pass eTICI 2B, and 242 and 279 patients with eTICI 2C/3 after 2 and ≥3 passe...

Research paper thumbnail of Factors influencing thrombectomy decision making for primary medium vessel occlusion stroke

Journal of NeuroInterventional Surgery

BackgroundWe aimed to explore the preference of stroke physicians to treat patients with primary ... more BackgroundWe aimed to explore the preference of stroke physicians to treat patients with primary medium vessel occlusion (MeVO) stroke with immediate endovascular treatment (EVT) in an international cross-sectional survey, as there is no clear guideline recommendation for EVT in these patients.MethodsIn the survey MeVO-Finding Rationales and Objectifying New Targets for IntervEntional Revascularization in Stroke (MeVO-FRONTIERS), participants were shown four cases of primary MeVOs (six scenarios per case) and asked whether they would treat those patients with EVT. Multivariable logistic regression with clustering by respondent was performed to assess factors influencing the decision to treat. Dominance analysis was performed to assess the influence of factors within the scenarios on decision making.ResultsOverall, 366 participants (56 women; 15%) from 44 countries provided 8784 answers to 24 scenarios. Most physicians (59.2%) would treat patients immediately with EVT. Younger patien...

Research paper thumbnail of Abstract P365: Effect of Radiological Thrombus Characteristics on Results of First-Line Endovascular Treatment Approach for Acute Ischemic Stroke

Stroke

Introduction: Pervious thrombi benefit more from intravenous thrombolysis, but the role of pervio... more Introduction: Pervious thrombi benefit more from intravenous thrombolysis, but the role of perviousness in endovascular treatment (EVT) is not completely clear. Thrombus length is negatively associated with outcome after EVT. Pervious, long thrombi may be more difficult to aspirate, or fragment more easily than non-pervious, short thrombi. We assessed the effect of perviousness and thrombus length on results of first-line aspiration thrombectomy in EVT, in comparison to stent-retrievers. Methods: We included MR CLEAN Registry patients (N=1526) with thin-slice imaging available, and aspiration or stent-retriever as first EVT attempt (N=391). Thrombus perviousness was measured by thrombus attenuation increase (Houndsfield Units; HU). Associations with 90-day modified Rankin Scale score (mRS), and final and first-pass reperfusion (eTICI 2B-3) were tested with adjusted logistic regression analyses. Results: Sixty-five (21%) patients were treated with first-line aspiration, 252 (79%) wit...

Research paper thumbnail of Abstract TMP2: Reduction of Time to Endovascular Treatment and Improved Outcomes After Ischemic Stroke in Routine Clinical Practice: Comparison of the MR CLEAN Registry First and Second Cohorts

Stroke

Introduction: Outcomes after endovascular treatment (EVT) for acute ischemic stroke are highly ti... more Introduction: Outcomes after endovascular treatment (EVT) for acute ischemic stroke are highly time dependent, but whether active reduction of time to treatment leads to better outcome has not been demonstrated. We compared data of the two subsequent MR CLEAN Registry cohorts, comprising all patients in the Netherlands who had EVT for acute ischemic stroke from 2014-2017, for a trend in time to treatment and its association with outcome. Methods: We compared workflow, successful reperfusion (eTICI 2B-3), NIHSS at 24h, functional outcome (mRS) at 90 days, occurrence of symptomatic intracranial hemorrhage (sICH) and mortality in patients with ischemic stroke and a proximal intracranial occlusion in the anterior circulation included in the second cohort of the Registry (June 2016-November 2017; n = 1779) to those in patients included in the first cohort (March 2014-June 2016; n = 1526) using logistic regression. Results: Baseline NIHSS was 16 in both cohorts. Times from onset-to-groin ...

Research paper thumbnail of Influence of Onset to Imaging Time on Radiological Thrombus Characteristics in Acute Ischemic Stroke

Frontiers in Neurology

Introduction: Radiological thrombus characteristics are associated with patient outcomes and trea... more Introduction: Radiological thrombus characteristics are associated with patient outcomes and treatment success after acute ischemic stroke. These characteristics could be expected to undergo time-dependent changes due to factors influencing thrombus architecture like blood stasis, clot contraction, and natural thrombolysis. We investigated whether stroke onset-to-imaging time was associated with thrombus length, perviousness, and density in the MR CLEAN Registry population.Methods: We included 245 patients with M1-segment occlusions and thin-slice baseline CT imaging from the MR CLEAN Registry, a nation-wide multicenter registry of patients who underwent endovascular treatment for acute ischemic stroke within 6.5 h of onset in the Netherlands. We used multivariable linear regression to investigate the effect of stroke onset-to-imaging time (per 5 min) on thrombus length (in mm), perviousness and density (both in Hounsfield Units). In the first model, we adjusted for age, sex, intrav...

Research paper thumbnail of Effect of age and baseline ASPECTS on outcomes in large-vessel occlusion stroke: results from the HERMES collaboration

Journal of NeuroInterventional Surgery

BackgroundPatient age and baseline Alberta Stroke Program Early CT score (ASPECTS) are both indep... more BackgroundPatient age and baseline Alberta Stroke Program Early CT score (ASPECTS) are both independent predictors of outcome in acute ischemic stroke patients treated with endovascular therapy (EVT). We assessed the combined effect of age and ASEPCTS on clinical outcome in acute ischemic stroke patients with LVO with and without EVT, and EVT treatment effect in different age/ASPECTS subgroups.MethodsThe HERMES collaboration pooled data of seven randomized controlled trials that tested the efficacy of EVT. Adjusted logistic regression was performed to test for multiplicative interaction of age and ASPECTS with the primary outcome (ordinal mRS) and secondary outcomes (mRS 0–2/0–1/0–3) in the EVT and control arms. Patients were then stratified by age (<75 vs ≥ 75 years) and ASPECTS (0–5/6–7/8–10), and adjusted effect-size estimates for the association of EVT were derived for the six age/ASPECTS subgroups.Results1735 patients were included in the analysis. There was no multiplicativ...

Research paper thumbnail of Value of repeated imaging in patients with a stroke who are transferred for endovascular treatment

Journal of NeuroInterventional Surgery, 2021

Background Patients with a stroke who are transferred to a comprehensive stroke center for endova... more Background Patients with a stroke who are transferred to a comprehensive stroke center for endovascular treatment (EVT) often undergo repeated neuroimaging prior to EVT. Objective To evaluate the yield of repeating imaging and its effect on treatment times. Methods We included adult patients with a large vessel occlusion (LVO) stroke who were referred to our hospital for EVT by primary stroke centers (2016–2019). We excluded patients who underwent repeated imaging because primary imaging was unavailable, incomplete, or of insufficient quality. Outcomes included treatment times and repeated imaging findings. Results Of 677 transferred LVO stroke, 551 were included. Imaging was repeated in 165/551 patients (30%), mostly because of clinical improvement (86/165 (52%)) or deterioration (40/165 (24%)). Patients who underwent repeated imaging had higher door-to-groin-times than patients without repeated imaging (median 43 vs 27 min, adjusted time difference: 20 min, 95% CI 15 to 25). Among...

Research paper thumbnail of Influence of intravenous alteplase on endovascular treatment decision-making in acute ischemic stroke due to primary medium-vessel occlusion: a case-based survey study

Journal of NeuroInterventional Surgery

BackgroundIntravenous alteplase is currently the only evidence-based treatment for medium-vessel ... more BackgroundIntravenous alteplase is currently the only evidence-based treatment for medium-vessel occlusion stroke (MeVO; M2/3, A2/3, and P2/3 vessel segment occlusions), but due to its limited efficacy, endovascular treatment (EVT) is increasingly performed in these patients. In this case-based survey study, we examined the influence of intravenous alteplase treatment on physicians’ decision-making for EVT in primary MeVO stroke.MethodsIn an international web-based survey among physicians involved in acute stroke care, participants provided their EVT decision for six quasi-identical fictional MeVO case scenarios (three with and without intravenous alteplase administered). Each scenario showed radiological images and clinical information in the form of a short case vignette. We compared EVT decisions (“immediate EVT”, “no EVT”, or “wait for alteplase effect” [in case scenarios with alteplase treatment only]) for case scenarios with and without alteplase treatment. Clustered multivari...

Research paper thumbnail of Worldwide anaesthesia use during endovascular treatment for medium vessel occlusion stroke

Interventional Neuroradiology

Introduction The optimal anaesthesia approach for endovascular treatment (EVT) in acute ischaemic... more Introduction The optimal anaesthesia approach for endovascular treatment (EVT) in acute ischaemic stroke is currently unknown. In stroke due to medium vessel occlusions (MeVO), the occluded vessels are particularly small and more difficult to access, especially in restless or uncooperative patients. In these patients, general anaesthesia (GA) may be preferred by physicians to prevent complications due to patient movement. We investigated physicians’ approaches to anaesthesia during EVT for MeVO stroke. Methods In a worldwide, case-based, online survey, physicians’ preferred anaesthesia approach during EVT for MeVO stroke was categorized as “initial GA”, “initial GA if necessary” (depending on patient cooperation), “no initial GA, but conversion if necessary” (start with local anaesthesia or conscious sedation), and “no GA”. Preferred anaesthesia approaches were reported overall and stratified by physician and patient characteristics. Results A total of 366 survey participants provid...

Research paper thumbnail of Quantified health and cost effects of faster endovascular treatment for large vessel ischemic stroke patients in the Netherlands

Journal of NeuroInterventional Surgery

BackgroundThe effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stro... more BackgroundThe effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population.MethodsA Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs.ResultsEVT administered 1 min faster resulted in a median NMB ...

Research paper thumbnail of Evaluating Outcome Prediction Models in Endovascular Stroke Treatment Using Baseline, Treatment, and Posttreatment Variables

Stroke: Vascular and Interventional Neurology

BACKGROUND Statistical models to predict outcomes after endovascular therapy for acute ischemic s... more BACKGROUND Statistical models to predict outcomes after endovascular therapy for acute ischemic stroke often incorporate baseline (pretreatment) variables only. We assessed the performance of stroke outcome prediction models for endovascular therapy in stroke in an iterative fashion using baseline, treatment‐related, and posttreatment variables. METHODS Data from the ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial were used to build 4 outcome prediction models using multivariable logistic regression: model 1 included baseline variables available before treatment decision making, model 2 included additional treatment‐related variables, model 3 additional posttreatment variables that become available early (within 24–48 hours), and model 4 later (beyond 48 hours) after endovascular therapy. The primary outcome was functional independence (90‐day Modified Rankin Scale score 0–2). Model performance was compared usin...

Research paper thumbnail of Patient and proxies’ attitudes towards deferred consent in randomised trials of acute treatment for stroke: A qualitative survey

European Stroke Journal

Introduction Deferral of consent for participation in a clinical study is a relatively novel proc... more Introduction Deferral of consent for participation in a clinical study is a relatively novel procedure, in which informed consent is obtained after randomisation and study treatment. Deferred consent can be used in emergency situations, where small therapeutic time windows limit possibilities for patients to provide informed consent. We aimed to investigate patients’ or their proxies’ experiences and opinions regarding deferred consent in acute stroke randomised trials. Patients and methods For this qualitative study, Dutch Collaboration for New Treatments of Acute Stroke (CONTRAST) trial participants were selected. Study participants were either patients or their proxies who provided consent and were selected with theoretical sampling based on patient characteristics. Semi-structured interviews were conducted face-to-face or by telephone. Themes and subthemes were iteratively defined. Results Twenty of the 23 interviewed participants (16 patients and 7 proxies) considered deferred ...

Research paper thumbnail of Which Acute Ischemic Stroke Patients Are Fast Progressors?

Stroke

Background and Purpose: Fast infarct progression in acute ischemic stroke has a severe impact on ... more Background and Purpose: Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics. Methods: Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail. Results: Fast infarct progression occurred in 15 of 43 includ...

Research paper thumbnail of Endovascular treatment effect diminishes with increasing thrombus perviousness: data from 7 acute ischaemic stroke trials

Stroke, 2021

BACKGROUND AND PURPOSE: Thrombus perviousness estimates residual flow along a thrombus in acute i... more BACKGROUND AND PURPOSE: Thrombus perviousness estimates residual flow along a thrombus in acute ischemic stroke, based on radiological images, and may influence the benefit of endovascular treatment for acute ischemic stroke. We aimed to investigate potential endovascular treatment (EVT) effect modification by thrombus perviousness. METHODS: We included 443 patients with thin-slice imaging available, out of 1766 patients from the pooled HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set of 7 randomized trials on EVT in the early window (most within 8 hours). Control arm patients (n=233) received intravenous alteplase if eligible (212/233; 91%). Intervention arm patients (n=210) received additional EVT (prior alteplase in 178/210; 85%). Perviousness was quantified by thrombus attenuation increase on admission computed tomography angiography compared with noncontrast computed tomography. Multivariable regression analyses were performed including multiplicative interaction terms between thrombus attenuation increase and treatment allocation. In case of significant interaction, subgroup analyses by treatment arm were performed. Our primary outcome was 90-day functional outcome (modified Rankin Scale score), resulting in an adjusted common odds ratio for a one-step shift towards improved outcome. Secondary outcomes were mortality, successful reperfusion (extended Thrombolysis in Cerebral Infarction score, 2B-3), and follow-up infarct volume (in mL). RESULTS: Increased perviousness was associated with improved functional outcome. After adding a multiplicative term of thrombus attenuation increase and treatment allocation, model fit improved significantly (P=0.03), indicating interaction between perviousness and EVT benefit. Control arm patients showed significantly better outcomes with increased perviousness (adjusted common odds ratio, 1.2 [95% CI, 1.1-1.3]). In the EVT arm, no significant association was found (adjusted common odds ratio, 1.0 [95% CI, 0.9-1.1]), and perviousness was not significantly associated with successful reperfusion. Follow-up infarct volume (12% [95% CI, 7.0-17] per 5 Hounsfield units) and chance of mortality (adjusted odds ratio, 0.83 [95% CI, 0.70-0.97]) decreased with higher thrombus attenuation increase in the overall population, without significant treatment interaction. CONCLUSIONS: Our study suggests that the benefit of best medical care including alteplase, compared with additional EVT, increases in patients with more pervious thrombi.

Research paper thumbnail of Bifurcation occlusions and endovascular treatment outcome in acute ischemic stroke

Journal of NeuroInterventional Surgery

BackgroundA thrombus in the M1 segment of the middle cerebral artery (MCA) can occlude this main ... more BackgroundA thrombus in the M1 segment of the middle cerebral artery (MCA) can occlude this main stem only or extend into the M1-M2 bifurcation. The occlusion pattern may affect endovascular treatment (EVT) success, as a bifurcated thrombus may be more prone to fragmentation during retrieval.ObjectiveTo investigate whether bifurcated thrombus patterns are associated with EVT procedural and clinical outcomes.MethodsOcclusion patterns of MCA thrombi on CT angiography from MR CLEAN Registry patients were classified into three groups: main stem occlusion, bifurcation occlusion extending into one M2 branch, and bifurcation occlusion extending into both M2 branches. Procedural parameters, procedural outcomes (reperfusion grade and embolization to new territory), and clinical outcomes (24-48 hour National Institutes of Health Stroke Scale [NIHSSFU] score, change in NIHSS scores between 24 and 48 hours and baseline ∆[NIHSS], and 90-day modified Rankin Scale [mRS] scores) were compared betwe...

Research paper thumbnail of Fully Automated Thrombus Segmentation on CT Images of Patients with Acute Ischemic Stroke

Diagnostics

Thrombus imaging characteristics are associated with treatment success and functional outcomes in... more Thrombus imaging characteristics are associated with treatment success and functional outcomes in stroke patients. However, assessing these characteristics based on manual annotations is labor intensive and subject to observer bias. Therefore, we aimed to create an automated pipeline for consistent and fast full thrombus segmentation. We used multi-center, multi-scanner datasets of anterior circulation stroke patients with baseline NCCT and CTA for training (n = 228) and testing (n = 100). We first found the occlusion location using StrokeViewer LVO and created a bounding box around it. Subsequently, we trained dual modality U-Net based convolutional neural networks (CNNs) to segment the thrombus inside this bounding box. We experimented with: (1) U-Net with two input channels for NCCT and CTA, and U-Nets with two encoders where (2) concatenate, (3) add, and (4) weighted-sum operators were used for feature fusion. Furthermore, we proposed a dynamic bounding box algorithm to adjust t...

Research paper thumbnail of WSO909632 Supplemental Material2 - Supplemental material for qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients

Supplemental material, WSO909632 Supplemental Material2 for qTICI: Quantitative assessment of bra... more Supplemental material, WSO909632 Supplemental Material2 for qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients by Haryadi Prasetya, Lucas A Ramos, Thabiso Epema, Kilian M Treurniet, Bart J Emmer, Ido R van den Wijngaard, Guang Zhang, Manon Kappelhof, Olvert A Berkhemer, Albert J Yoo, Yvo BEWM Roos, Robert J van Oostenbrugge, Diederik WJ Dippel, Wim H van Zwam, Aad van der Lugt, Bas AJM de Mol, Charles BLM Majoie, Ed van Bavel, Henk A Marquering and on behalf of the MR CLEAN Registry Investigators in International Journal of Stroke

Research paper thumbnail of WSO909632 Supplemental Material1 - Supplemental material for qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients

Supplemental material, WSO909632 Supplemental Material1 for qTICI: Quantitative assessment of bra... more Supplemental material, WSO909632 Supplemental Material1 for qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients by Haryadi Prasetya, Lucas A Ramos, Thabiso Epema, Kilian M Treurniet, Bart J Emmer, Ido R van den Wijngaard, Guang Zhang, Manon Kappelhof, Olvert A Berkhemer, Albert J Yoo, Yvo BEWM Roos, Robert J van Oostenbrugge, Diederik WJ Dippel, Wim H van Zwam, Aad van der Lugt, Bas AJM de Mol, Charles BLM Majoie, Ed van Bavel, Henk A Marquering and on behalf of the MR CLEAN Registry Investigators in International Journal of Stroke

Research paper thumbnail of Improvements in Endovascular Treatment for Acute Ischemic Stroke: A Longitudinal Study in the MR CLEAN Registry

Stroke

Background: We evaluated data from all patients in the Netherlands who underwent endovascular tre... more 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 p...

Research paper thumbnail of Abstract 75: Hemorrhagic Transformation After Acute Ischemic Stroke Due to a Large Vessel Occlusion is Associated With Less Treatment Benefit

Stroke

Introduction: Intracranial hemorrhage after acute ischemic stroke patients manifests as natural p... more Introduction: Intracranial hemorrhage after acute ischemic stroke patients manifests as natural progression or as a complication of treatment with potential subsequent neurological deterioration. Currently it is unclear whether these hemorrhagic transformations (HT) contribute to the poorer functional outcomes observed in patients with large infarcts. The purpose of this study is to assess the association of HT with follow-up infarct volume (FIV) and functional outcome at 90 days after AIS. Additionally, we determined whether the development of HT was associated with a diminished endovascular therapy (EVT) effect. Methods: All patients from the HERMES collaboration with follow-up imaging were included. HERMES is pooled data from seven randomized controlled trials that assessed the efficacy and safety of EVT compared to usual care. Patients with HT were identified according to the ECASS classification and FIV was assessed on CT or MRI. Infarct and hemorrhage were included in the FIV....

Research paper thumbnail of Successful reperfusion in relation to the number of passes: comparing outcomes of first pass expanded Treatment In Cerebral Ischemia (eTICI) 2B with multiple-pass eTICI 3

Journal of NeuroInterventional Surgery

BackgroundHigher expanded Treatment In Cerebral Ischemia (eTICI) reperfusion scores after endovas... more BackgroundHigher 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.MethodsWe 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.ResultsWe included 699 patients: 178 patients with single-pass eTICI 2B, and 242 and 279 patients with eTICI 2C/3 after 2 and ≥3 passe...

Research paper thumbnail of Factors influencing thrombectomy decision making for primary medium vessel occlusion stroke

Journal of NeuroInterventional Surgery

BackgroundWe aimed to explore the preference of stroke physicians to treat patients with primary ... more BackgroundWe aimed to explore the preference of stroke physicians to treat patients with primary medium vessel occlusion (MeVO) stroke with immediate endovascular treatment (EVT) in an international cross-sectional survey, as there is no clear guideline recommendation for EVT in these patients.MethodsIn the survey MeVO-Finding Rationales and Objectifying New Targets for IntervEntional Revascularization in Stroke (MeVO-FRONTIERS), participants were shown four cases of primary MeVOs (six scenarios per case) and asked whether they would treat those patients with EVT. Multivariable logistic regression with clustering by respondent was performed to assess factors influencing the decision to treat. Dominance analysis was performed to assess the influence of factors within the scenarios on decision making.ResultsOverall, 366 participants (56 women; 15%) from 44 countries provided 8784 answers to 24 scenarios. Most physicians (59.2%) would treat patients immediately with EVT. Younger patien...

Research paper thumbnail of Abstract P365: Effect of Radiological Thrombus Characteristics on Results of First-Line Endovascular Treatment Approach for Acute Ischemic Stroke

Stroke

Introduction: Pervious thrombi benefit more from intravenous thrombolysis, but the role of pervio... more Introduction: Pervious thrombi benefit more from intravenous thrombolysis, but the role of perviousness in endovascular treatment (EVT) is not completely clear. Thrombus length is negatively associated with outcome after EVT. Pervious, long thrombi may be more difficult to aspirate, or fragment more easily than non-pervious, short thrombi. We assessed the effect of perviousness and thrombus length on results of first-line aspiration thrombectomy in EVT, in comparison to stent-retrievers. Methods: We included MR CLEAN Registry patients (N=1526) with thin-slice imaging available, and aspiration or stent-retriever as first EVT attempt (N=391). Thrombus perviousness was measured by thrombus attenuation increase (Houndsfield Units; HU). Associations with 90-day modified Rankin Scale score (mRS), and final and first-pass reperfusion (eTICI 2B-3) were tested with adjusted logistic regression analyses. Results: Sixty-five (21%) patients were treated with first-line aspiration, 252 (79%) wit...

Research paper thumbnail of Abstract TMP2: Reduction of Time to Endovascular Treatment and Improved Outcomes After Ischemic Stroke in Routine Clinical Practice: Comparison of the MR CLEAN Registry First and Second Cohorts

Stroke

Introduction: Outcomes after endovascular treatment (EVT) for acute ischemic stroke are highly ti... more Introduction: Outcomes after endovascular treatment (EVT) for acute ischemic stroke are highly time dependent, but whether active reduction of time to treatment leads to better outcome has not been demonstrated. We compared data of the two subsequent MR CLEAN Registry cohorts, comprising all patients in the Netherlands who had EVT for acute ischemic stroke from 2014-2017, for a trend in time to treatment and its association with outcome. Methods: We compared workflow, successful reperfusion (eTICI 2B-3), NIHSS at 24h, functional outcome (mRS) at 90 days, occurrence of symptomatic intracranial hemorrhage (sICH) and mortality in patients with ischemic stroke and a proximal intracranial occlusion in the anterior circulation included in the second cohort of the Registry (June 2016-November 2017; n = 1779) to those in patients included in the first cohort (March 2014-June 2016; n = 1526) using logistic regression. Results: Baseline NIHSS was 16 in both cohorts. Times from onset-to-groin ...

Research paper thumbnail of Influence of Onset to Imaging Time on Radiological Thrombus Characteristics in Acute Ischemic Stroke

Frontiers in Neurology

Introduction: Radiological thrombus characteristics are associated with patient outcomes and trea... more Introduction: Radiological thrombus characteristics are associated with patient outcomes and treatment success after acute ischemic stroke. These characteristics could be expected to undergo time-dependent changes due to factors influencing thrombus architecture like blood stasis, clot contraction, and natural thrombolysis. We investigated whether stroke onset-to-imaging time was associated with thrombus length, perviousness, and density in the MR CLEAN Registry population.Methods: We included 245 patients with M1-segment occlusions and thin-slice baseline CT imaging from the MR CLEAN Registry, a nation-wide multicenter registry of patients who underwent endovascular treatment for acute ischemic stroke within 6.5 h of onset in the Netherlands. We used multivariable linear regression to investigate the effect of stroke onset-to-imaging time (per 5 min) on thrombus length (in mm), perviousness and density (both in Hounsfield Units). In the first model, we adjusted for age, sex, intrav...

Research paper thumbnail of Effect of age and baseline ASPECTS on outcomes in large-vessel occlusion stroke: results from the HERMES collaboration

Journal of NeuroInterventional Surgery

BackgroundPatient age and baseline Alberta Stroke Program Early CT score (ASPECTS) are both indep... more BackgroundPatient age and baseline Alberta Stroke Program Early CT score (ASPECTS) are both independent predictors of outcome in acute ischemic stroke patients treated with endovascular therapy (EVT). We assessed the combined effect of age and ASEPCTS on clinical outcome in acute ischemic stroke patients with LVO with and without EVT, and EVT treatment effect in different age/ASPECTS subgroups.MethodsThe HERMES collaboration pooled data of seven randomized controlled trials that tested the efficacy of EVT. Adjusted logistic regression was performed to test for multiplicative interaction of age and ASPECTS with the primary outcome (ordinal mRS) and secondary outcomes (mRS 0–2/0–1/0–3) in the EVT and control arms. Patients were then stratified by age (<75 vs ≥ 75 years) and ASPECTS (0–5/6–7/8–10), and adjusted effect-size estimates for the association of EVT were derived for the six age/ASPECTS subgroups.Results1735 patients were included in the analysis. There was no multiplicativ...

Research paper thumbnail of Value of repeated imaging in patients with a stroke who are transferred for endovascular treatment

Journal of NeuroInterventional Surgery, 2021

Background Patients with a stroke who are transferred to a comprehensive stroke center for endova... more Background Patients with a stroke who are transferred to a comprehensive stroke center for endovascular treatment (EVT) often undergo repeated neuroimaging prior to EVT. Objective To evaluate the yield of repeating imaging and its effect on treatment times. Methods We included adult patients with a large vessel occlusion (LVO) stroke who were referred to our hospital for EVT by primary stroke centers (2016–2019). We excluded patients who underwent repeated imaging because primary imaging was unavailable, incomplete, or of insufficient quality. Outcomes included treatment times and repeated imaging findings. Results Of 677 transferred LVO stroke, 551 were included. Imaging was repeated in 165/551 patients (30%), mostly because of clinical improvement (86/165 (52%)) or deterioration (40/165 (24%)). Patients who underwent repeated imaging had higher door-to-groin-times than patients without repeated imaging (median 43 vs 27 min, adjusted time difference: 20 min, 95% CI 15 to 25). Among...

Research paper thumbnail of Influence of intravenous alteplase on endovascular treatment decision-making in acute ischemic stroke due to primary medium-vessel occlusion: a case-based survey study

Journal of NeuroInterventional Surgery

BackgroundIntravenous alteplase is currently the only evidence-based treatment for medium-vessel ... more BackgroundIntravenous alteplase is currently the only evidence-based treatment for medium-vessel occlusion stroke (MeVO; M2/3, A2/3, and P2/3 vessel segment occlusions), but due to its limited efficacy, endovascular treatment (EVT) is increasingly performed in these patients. In this case-based survey study, we examined the influence of intravenous alteplase treatment on physicians’ decision-making for EVT in primary MeVO stroke.MethodsIn an international web-based survey among physicians involved in acute stroke care, participants provided their EVT decision for six quasi-identical fictional MeVO case scenarios (three with and without intravenous alteplase administered). Each scenario showed radiological images and clinical information in the form of a short case vignette. We compared EVT decisions (“immediate EVT”, “no EVT”, or “wait for alteplase effect” [in case scenarios with alteplase treatment only]) for case scenarios with and without alteplase treatment. Clustered multivari...

Research paper thumbnail of Worldwide anaesthesia use during endovascular treatment for medium vessel occlusion stroke

Interventional Neuroradiology

Introduction The optimal anaesthesia approach for endovascular treatment (EVT) in acute ischaemic... more Introduction The optimal anaesthesia approach for endovascular treatment (EVT) in acute ischaemic stroke is currently unknown. In stroke due to medium vessel occlusions (MeVO), the occluded vessels are particularly small and more difficult to access, especially in restless or uncooperative patients. In these patients, general anaesthesia (GA) may be preferred by physicians to prevent complications due to patient movement. We investigated physicians’ approaches to anaesthesia during EVT for MeVO stroke. Methods In a worldwide, case-based, online survey, physicians’ preferred anaesthesia approach during EVT for MeVO stroke was categorized as “initial GA”, “initial GA if necessary” (depending on patient cooperation), “no initial GA, but conversion if necessary” (start with local anaesthesia or conscious sedation), and “no GA”. Preferred anaesthesia approaches were reported overall and stratified by physician and patient characteristics. Results A total of 366 survey participants provid...

Research paper thumbnail of Quantified health and cost effects of faster endovascular treatment for large vessel ischemic stroke patients in the Netherlands

Journal of NeuroInterventional Surgery

BackgroundThe effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stro... more BackgroundThe effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population.MethodsA Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs.ResultsEVT administered 1 min faster resulted in a median NMB ...

Research paper thumbnail of Evaluating Outcome Prediction Models in Endovascular Stroke Treatment Using Baseline, Treatment, and Posttreatment Variables

Stroke: Vascular and Interventional Neurology

BACKGROUND Statistical models to predict outcomes after endovascular therapy for acute ischemic s... more BACKGROUND Statistical models to predict outcomes after endovascular therapy for acute ischemic stroke often incorporate baseline (pretreatment) variables only. We assessed the performance of stroke outcome prediction models for endovascular therapy in stroke in an iterative fashion using baseline, treatment‐related, and posttreatment variables. METHODS Data from the ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial were used to build 4 outcome prediction models using multivariable logistic regression: model 1 included baseline variables available before treatment decision making, model 2 included additional treatment‐related variables, model 3 additional posttreatment variables that become available early (within 24–48 hours), and model 4 later (beyond 48 hours) after endovascular therapy. The primary outcome was functional independence (90‐day Modified Rankin Scale score 0–2). Model performance was compared usin...

Research paper thumbnail of Patient and proxies’ attitudes towards deferred consent in randomised trials of acute treatment for stroke: A qualitative survey

European Stroke Journal

Introduction Deferral of consent for participation in a clinical study is a relatively novel proc... more Introduction Deferral of consent for participation in a clinical study is a relatively novel procedure, in which informed consent is obtained after randomisation and study treatment. Deferred consent can be used in emergency situations, where small therapeutic time windows limit possibilities for patients to provide informed consent. We aimed to investigate patients’ or their proxies’ experiences and opinions regarding deferred consent in acute stroke randomised trials. Patients and methods For this qualitative study, Dutch Collaboration for New Treatments of Acute Stroke (CONTRAST) trial participants were selected. Study participants were either patients or their proxies who provided consent and were selected with theoretical sampling based on patient characteristics. Semi-structured interviews were conducted face-to-face or by telephone. Themes and subthemes were iteratively defined. Results Twenty of the 23 interviewed participants (16 patients and 7 proxies) considered deferred ...

Research paper thumbnail of Which Acute Ischemic Stroke Patients Are Fast Progressors?

Stroke

Background and Purpose: Fast infarct progression in acute ischemic stroke has a severe impact on ... more Background and Purpose: Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics. Methods: Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail. Results: Fast infarct progression occurred in 15 of 43 includ...