Symptomatic non-stenotic carotid disease: current challenges and opportunities for diagnosis and treatment.

Symptomatic non-stenotic carotid plaques (SyNC) are an under-researched and under-recognized source of stroke. Various imaging markers of non-stenotic carotid plaques that are associated with stroke risk have been identified, but these causal relationships need to be confirmed in additional prospective studies. Currently, there exists neither a standardized SyNC definition nor a dedicated set of imaging protocols, although researchers have started to address these shortcomings. Moreover, many neuroradiologists are still unaware of the condition, and hence do not comment on high-risk plaque features other than stenosis in their reports. Regarding SyNC treatment, scant data exist as to whether and to what extent medical, interventional and surgical treatments could influence the course of the disease; the relative lack of data on the 'natural' history of untreated SyNC makes treatment comparisons difficult. In our opinion, endovascular SyNC treatment represents the most promising treatment option for SyNC, since it allows for targeted elimination of the embolic source, with few systemic side effects and without the need for general anesthesia. However, currently available carotid devices are designed to treat stenotic lesions, and thus are not optimally designed for SyNC. Developing a device specifically tailored to SyNC could be an important step towards establishing endovascular SyNC treatment in clinical practice. In this review, we provide an overview of the current state of evidence with regard to epidemiological, clinical and imaging features of SyNC, propose a SyNC definition based on imaging and clinical features, and outline a possible pathway towards evidence-based SyNC therapies, with a special focus on endovascular SyNC treatment.

Factors influencing thrombectomy decision making for primary medium vessel occlusion stroke.

BACKGROUND: We 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. METHODS: In 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. RESULTS: Overall, 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 patient age (incidence rate ratio (IRR) 1.24, 99% CI 1.19 to 1.30), higher National Institutes of Health Stroke Scale (NIHSS) score (IRR 1.69, 99% CI 1.57 to 1.82), and small core volume (IRR 1.35, 99% CI 1.24 to 1.46) were positively associated with the decision to treat with EVT. Interventionalists (IRR 1.26, 99% CI 1.01 to 1.56) were more likely to treat patients with MeVO immediately with EVT. In the dominance analysis, factors influencing the decision in favor of EVT were (in order of importance): baseline NIHSS, core volume, alteplase use, patients' age, and occlusion site. CONCLUSIONS: Most physicians in this survey were interventionalists and would treat patients with MeVO stroke immediately with EVT. This finding supports the need for robust clinical evidence.

Predictors and clinical impact of infarct progression rate in the ESCAPE-NA1 trial.

BACKGROUND: Determining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-making, and outcome prognostication. OBJECTIVE: To estimate infarct progression rate in patients with AIS with large vessel occlusion (LVO) and determine its predictors and impact on clinical outcome. METHODS: Data are from the ESCAPE-NA1 Trial. Patients with AIS with time from last known well to randomization <6 hours and near-complete reperfusion following endovascular treatment were included. Infarct growth rate (mL/h) was estimated by dividing 24 hour infarct volume (measured by non-contrast CT or diffusion-weighted magnetic resonance imaging) by time from last known well to reperfusion. Multivariable linear regression was used to assess the association of patient baseline variables with log-transformed infarct progression rate. The association of infarct progression rate and good outcome (modified Rankin Scale score 0-2) was determined using multivariable logistic regression. RESULTS: Four hundred and nine patients were included in the study. Median infarct progression rate was 4.74 mL/h (IQR 1.25-14.84). Collateral status (ß: -0.81 (95% CI -1.20 to -0.41)), Alberta Stroke Program Early CT Score (ASPECTS, ß: -0.34 (95% CI -0.46 to -0.23)), blood glucose(ß: 0.09 (95% CI 0.02 to 0.16)), and National Institutes of Health Stroke Scale (NIHS score (ß: 0.07 (95% CI 0.04 to 0.10)) were associated with log-transformed infarct progression rate. Clinical and imaging baseline variables explained 23% of the variance in infarct progression rate. Infarct progression rate was significantly associated with good outcome (aOR per 1 mL/h increase: 0.96 (95% CI 0.95 to 0.98)). CONCLUSION: In this sample of patients presenting within the early time window with LVO and near-complete recanalization, infarct progression rate was significantly associated with good outcome. A significant association between ASPECTS, collateral status, blood glucose, and NIHSS score was observed, but baseline imaging and clinical characteristics explained only a small proportion of the interindividual variance. More research on measurable factors affecting infarct growth is needed.

Is concurrent intravenous alteplase in patients undergoing endovascular treatment for large vessel occlusion stroke cost-effective even if the cost of alteplase is only US$1?

BACKGROUND: The added value of intravenous (IV) alteplase in large vessel occlusion (LVO) stroke over and beyond endovascular treatment (EVT) is controversial. We compared the long-term costs and cost-effectiveness of a direct-to-EVT paradigm in LVO stroke patients presenting directly to the mothership hospital to concurrent EVT and IV alteplase. METHODS: We used a decision model consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes. Outcome data were from the DIRECT-MT trial (NCT03469206). Incremental cost-effectiveness ratios and net monetary benefits were calculated and probabilistic sensitivity analysis was performed. Analysis was performed from a healthcare perspective and a societal perspective using both a minimal assumed alteplase cost of US$1 and true alteplase cost. RESULTS: When assuming a minimal cost of alteplase of $1, EVT with concurrent IV alteplase resulted in incremental lifetime cost of $5664 (healthcare perspective)/$4804 (societal perspective) and a decrement of 0.25 quality-adjusted life years (QALYs) compared with EVT only, indicating dominance of the EVT only approach. Net monetary benefits were consistently higher for EVT only compared with EVT with concurrent alteplase. Probabilistic sensitivity analysis showed increased costs without an increase in QALYs for EVT and concurrent IV alteplase compared with EVT only. Results were even more in favor of EVT when the true cost of alteplase was used for analysis. CONCLUSION: EVT without concurrent alteplase is the preferred strategy from a health economic standpoint.

Endovascular treatment of anterior cerebral artery occlusions.

There are limited data on endovascular treatment (EVT) for anterior cerebral artery (ACA) occlusions. This review focuses on aspects related to ACA EVT: ACA anatomy, clinical and imaging findings, prognosis of ACA stroke, and ACA thrombectomy techniques. The ACA anatomy, and the regions supplied by the ACA, are highly variable; frequent anatomical variants include azygos ACA, triplicated ACA and fenestrations of the anterior communicating artery. ACA occlusions can be classified based on occlusion location, their continuity with other vessel occlusions (isolated ACA occlusion vs ACA occlusion as part of a carotid T occlusion) and etiology (primary-spontaneous ACA occlusion, vs secondary-spontaneous or iatrogenic due to clot fragmentation/migration). Symptoms of ACA stroke differ in severity and nature due to large inter-individual variations in territorial ACA blood supply. Generally, ACA strokes are severely disabling, and the typical clinical hallmark is a motor deficit of the contralateral lower extremity. Advanced imaging (CT perfusion, multiphase CT angiography) increases the likelihood of the correct diagnosis of ACA stroke and should be obtained on routine basis.Available data for ACA EVT suggest its feasibility and safety while clinical outcomes are often unfavorable with conservative management. Therefore, the potential benefit of EVT seems obvious. An optimized endovascular approach for ACA thrombectomy comprises the development and use of smaller and softer devices that can be delivered through small microcatheters with an optimized vector of force. Ultimately, generating high-level evidence for ACA EVT from randomized trials remains warranted.

A review of endovascular treatment for medium vessel occlusion stroke.

Medium-vessel occlusions (MeVOs), that is, occlusions of the M2/3 middle cerebral artery, A2/3 anterior cerebral artery, and P2/3 posterior cerebral artery segments, account for 25%-40% of all acute ischemic stroke cases. Clinical outcomes of MeVO stroke with intravenous thrombolysis, which is the current standard of care, are moderate at best. With improving imaging technologies and a growing literature, MeVOs are increasingly recognized as a target for endovascular treatment (EVT). For the time being, there is limited but promising evidence for the safety and efficacy of MeVO EVT, and many neurointerventionists are already routinely offering EVT for MeVO stroke, despite the lack of clear guideline recommendations. In this article, we review the evidence on endovascular treatment for MeVO stroke and summarize the available literature on current imaging strategies, commonly used EVT selection criteria, EVT techniques, and outcome assessment for MeVO stroke.

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

BACKGROUND: Patient 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. METHODS: The 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. RESULTS: 1735 patients were included in the analysis. There was no multiplicative interaction between age and ASPECTS on clinical outcomes. In the exploratory subgroup analysis, we found a nominally negative point estimate for the association of EVT with clinical outcome in the ASPECTS 0-5/age ≥75, subgroup (acOR 0.36, 95% CI 0.07 to 1.89). The point estimate for moderate outcome (mRS0-3) nominally favored EVT (aOR 1.24, 95% CI 0.16 to 9.84). In all other subgroups, effect size-estimates consistently favored EVT. CONCLUSION: There was no multiplicative interaction of age and ASPECTS on clinical outcomes in EVT or control arm patients. Outcomes in patients ≥75 years with ASPECTS 0-5 were poor, irrespective of treatment. Further investigation to define the role of EVT and range of acceptable outcomes in this subgroup is warranted.

Current and future usefulness and potential of virtual simulation in improving outcomes and reducing complications in endovascular treatment of unruptured intracranial aneurysms.

BACKGROUND: Simulation training has been used in the aviation industry and surgical specialties for many years, but integration into neurointerventional practice is lagging behind. OBJECTIVE: To investigate how neurointerventionalists perceive the usefulness and limitations of simulation tools for the treatment of unruptured intracranial aneurysms (UIAs), and to identify simulation applications that were perceived to be most valuable for endovascular UIA treatment. METHODS: A web-based international multidisciplinary survey was conducted among neurointerventionalists. Participants were asked for their perceptions on the usefulness of current simulation tools and the potential impact of future simulation tools in endovascular UIA treatment. They identified simulation applications that could add most value to endovascular UIA treatment and help to specifically reduce endovascular UIA treatment complications. RESULTS: 233 neurointerventionalists from 38 countries completed the survey, most of whom (157/233 (67.4%)) had access to a simulator as a trainee, but only 15.3% used it frequently. Most participants (117/233 (50.2%)) considered currently available simulation tools relatively useful for endovascular UIA treatment, with greater value for trainees than for staff. Simulation of new devices (147/233 (63.1%)) and virtual practice runs in individual patient anatomy (119/233 (51.1%)) were considered most valuable for reducing endovascular UIA treatment complications. CONCLUSION: Although neurointerventionalists perceived currently available simulation tools relatively useful, they did not use them regularly during their training. A priori testing of new devices and practice runs in individual patient anatomy in a virtual environment were thought to have the greatest potential for reducing endovascular UIA treatment complications.

Imaging criteria across pivotal randomized controlled trials for late window thrombectomy patient selection.

BACKGROUND: The DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion imaging criteria. The ESCAPE NA1-trial selected patients based on non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) and multiphase CT angiography (CTA) collateral status. This study compares baseline characteristics, workflow, and outcomes in the EVT arms of DAWN and DEFUSE-3 with late-window patients from the EVT-only arm of ESCAPE-NA1. METHODS: Aggregate data on baseline characteristics, workflow, reperfusion quality, final infarct volume, and clinical outcomes (modified Rankin Score [mRS] at 90 days) in subjects enrolled in the DAWN and DEFUSE-3 EVT arms were compared with similar data from the ESCAPE-NA1 control arm (EVT-only arm) presenting beyond 6 hours from LKW using descriptive statistics. RESULTS: Baseline characteristics among late-window patients in the ESCAPE NA1 trial were similar to those in the DAWN and DEFUSE-3 EVT arms. Median time from LKW-to-puncture in subjects enrolled in the ESCAPE NA1 trial was 9 hrs (IQR: 7.5-11 hours) when compared with DAWN (n=107; 12.8 hours, IQR: 10.6-16.7 hours) and DEFUSE-3 (n=92; 11.5 hours, IQR: 9.2-12.8 hours). Median post-treatment infarct-volume was largest in the ESCAPE NA1-patients (47 mL [IQR: 19-146] vs median 8 mL [IQR: 0-48] in the DAWN group and 35 mL [IQR: 18-82] in DEFUSE-3), while % mRS 0-2 at 90 days were similar across the three trials (ESCAPE NA1: 50/111 [45%], DAWN: 52/107 [49%], DEFUSE-3: 41/92 [45%]). CONCLUSION: Patients enrolled beyond 6 hours from LKW in the ESCAPE-NA1 trial based on NCCT-ASPECTS and mCTA had similar clinical outcomes when compared with patients selected by perfusion imaging in the DAWN and DEFUSE-3 trials.

Impact and prevention of errors in endovascular treatment of unruptured intracranial aneurysms.

BACKGROUND: Preventing errors and complications in neurointervention is crucial, particularly in the treatment of unruptured intracranial aneurysms (UIAs), where the natural history is generally benign, and the margin of treatment benefit small. We aimed to investigate how neurointerventionalists perceive the importance and frequency of errors and the resulting complications in endovascular UIA treatment, and which steps could be taken to prevent them. METHODS: An international multidisciplinary survey was conducted among neurointerventionalists. Participants provided their demographic characteristics and neurointerventional treatment volume. They were asked about their perceptions on the importance and frequency of different errors in endovascular UIA treatment, and which solutions they thought to be most effective in preventing these errors. RESULTS: Two-hundred-thirty-three neurointerventionalists from 38 countries participated in the survey. Participants identified errors in technical execution as the most common source of complications in endovascular UIA treatment (40.4% thought these errors constituted a relatively or very large proportion of all complication sources), closely followed by errors in decision-making/indication (32.2%) and errors related to management of unexpected events (28.4%). Simulation training was thought to be most effective in reducing technical errors, while cognitive errors were believed to be best minimized by abandoning challenging procedures, more honest discussion of complications and better standardization of procedure steps. CONCLUSION: Neurointerventionalists perceived both technical and cognitive errors to be important sources of complications in endovascular UIA treatment. Simulation training, a cultural change, higher acceptance of bail-out strategies and better standardization of procedures were perceived to be most effective in preventing these.

Workflow patterns and potential for optimization in endovascular stroke treatment across the world: results from a multinational survey.

BACKGROUND: The benefit of endovascular treatment (EVT) is highly time-dependent, and treatment delays reduce patients' chances to achieve a good outcome. In this survey-based study, we aimed to evaluate current in-hospital EVT workflow characteristics across different countries and hospital settings, and to quantify the time-savings that could be achieved by optimizing particular workflow steps. METHODS: In a multinational survey, neurointerventionalists were asked to provide specific information about EVT workflows in their current working environment. Workflow characteristics were summarized using descriptive statistics and stratified by country and physician characteristics, such as age, career stage, personal and institutional caseload. RESULTS: Among 248 respondents from 48 countries, pre-notification of the neurointerventional team was used in 70% of cases. The emergency department (ED) and CT scanner, and the CT scanner and neuroangiography suite, were on different floors in 23% and 38%, respectively. Redundant procedures in the ED were often routinely performed, such as chest x-rays (in 6%). General anesthesia was the most frequently used anesthesia protocol for EVT (42%), and an anesthesiologist was available in 82% for this purpose. 52% of the participants used a pre-prepared EVT kit. CONCLUSION: The current structure of EVT workflows offers possibilities for improvement. While some bottlenecks, such as the spatial department set-up, cannot easily be resolved, pre-notification tools and pre-prepared EVT kits are more straightforward to implement and could help to reduce treatment delays, and thereby improve patient outcomes.

Time of day and endovascular treatment decision in acute stroke with relative endovascular treatment indication: insights from UNMASK EVT international survey.

BACKGROUND AND PURPOSE: The decision to proceed with endovascular thrombectomy should ideally be made independent of inconvenience factors, such as daytime. We assessed the influence of patient presentation time on endovascular therapy decision making under current local resources and assumed ideal conditions in acute ischemic stroke with level 2B evidence for endovascular treatment. METHODS AND MATERIALS: In an international cross sectional survey, 607 stroke physicians from 38 countries were asked to give their treatment decisions to 10 out of 22 randomly assigned case scenarios. Eleven scenarios had level 2B evidence for endovascular treatment: 7 daytime scenarios (7:00 am-5:00 pm) and four night time cases (5:01 pm- 6:59 am). Participants provided their treatment approach assuming (A) there were no practice constraints and (B) under their current local resources. Endovascular treatment decisions in the 11 scenarios were analyzed according to presentation time with adjustment for patient and physician characteristics. RESULTS: Participants selected endovascular therapy in 74.2% under assumed ideal conditions, and 70.7% under their current local resources of night time scenarios, and in 67.2% and 63.8% of daytime scenarios. Night time presentation did not increase the probability of a treatment decision against endovascular therapy under current local resources or assumed ideal conditions. CONCLUSION: Presentation time did not influence endovascular treatment decision making in stroke patients in this international survey.

Endovascular treatment decision in acute stroke: does physician gender matter? Insights from UNMASK EVT, an international, multidisciplinary survey.

BACKGROUND AND PURPOSE: Differences in the treatment practice of female and male physicians have been shown in several medical subspecialties. It is currently not known whether this also applies to endovascular stroke treatment. The purpose of this study was to explore whether there are differences in endovascular treatment decisions made by female and male stroke physicians and neurointerventionalists. METHODS: In an international survey, stroke physicians and neurointerventionalists were randomly assigned 10 case scenarios and asked how they would treat the patient: (A) assuming there were no external constraints and (B) given their local working conditions. Descriptive statistics were used to describe baseline demographics, and the adjusted OR for physician gender as a predictor of endovascular treatment decision was calculated using logistic regression. RESULTS: 607 physicians (97 women, 508 men, 2 who did not wish to declare) participated in this survey. Physician gender was neither a significant predictor for endovascular treatment decision under assumed ideal conditions (endovascular therapy was favored by 77.0% of female and 79.3% of male physicians, adjusted OR 1.03, P=0.806) nor under current local resources (endovascular therapy was favored by 69.1% of female and 76.9% of male physicians, adjusted OR 1.03, P=0.814). CONCLUSION: Endovascular therapy decision making between male and female physicians did not differ under assumed ideal conditions or under current local resources.