Evidence gaps in endovascular treatment of acute ischemic stroke

In this PhD thesis, current evidence gaps in endovascular treatment of acute ischemic stroke are discussed. Followed by an introduction in chapter 1, we first discuss the clinical course of acute ischemic stroke due to medium vessel occlusion in chapter 2, which is not as benign as commonly assumed. In chapters 3 and 4, we assess the combined effect of baseline variables on post-stroke outcome, namely the combined effect of age and Alberta Stroke Program Early CT Score (ASPECTS) in chapter 3, and the combined effect of age and National Institutes of Health Stroke Scale (NIHSS) in chapter 4. We found no evidence of interaction between age and ASPECTS, or age and NIHSS. We further assessed the impact of different infarct patterns and tissue specific infarct volumes on 24-hour follow-up imaging after endovascular treatment in chapter 5, and found that certain infarct patterns, such as a territorial infarct pattern, are independent strong predictors of poor outcome, even when adjusting for total infarct volume. In chapter 6, we analyzed features that distinguish patients with and without fast infarct progression, and showed that cerebral vascular anatomy seems to be the most important predictor of fast infarct progression. Chapter 8 summarizes a consensus statement on antiplatelet management for carotid stenting in the setting of endovascular treatment, and chapter 9 investigates starting points for improving in-hospital acute stroke workflow efficiency. Chapter 10 provides a summary and an outlook on future directions in acute ischemic stroke research and management

Comparison of Pipeline Embolization Device Sizing Based on Conventional 2D Measurements and Virtual Simulation Using the Sim&Size Software: An Agreement Study

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Effect of Pre- and In-Hospital Delay on Reperfusion in Acute Ischemic Stroke Mechanical Thrombectomy.

Post hoc analyses of randomized controlled clinical trials evaluating mechanical thrombectomy have suggested that admission-to-groin-puncture (ATG) delays are associated with reduced reperfusion rates. Purpose of this analysis was to validate this association in a real-world cohort and to find associated factors and confounders for prolonged ATG intervals. Patients included into the BEYOND-SWIFT cohort (Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the Solitaire FR With the Intention for Thrombectomy; https://www.clinicaltrials.gov; Unique identifier: NCT03496064) were analyzed (n=2386). Association between baseline characteristics and ATG was evaluated using mixed linear regression analysis. The effect of increasing symptom-onset-to-admission and ATG intervals on successful reperfusion (defined as Thrombolysis in Cerebral Infarction [TICI] 2b-3) was evaluated using logistic regression analysis adjusting for potential confounders. Median ATG was 73 minutes. Prolonged ATG intervals were associated with the use of magnetic resonance imaging (+19.1 [95% CI, +9.1 to +29.1] minutes), general anesthesia (+12.1 [95% CI, +3.7 to +20.4] minutes), and borderline indication criteria, such as lower National Institutes of Health Stroke Scale, late presentations, or not meeting top-tier early time window eligibility criteria (+13.8 [95% CI, +6.1 to +21.6] minutes). There was a 13% relative odds reduction for TICI 2b-3 (adjusted odds ratio [aOR], 0.87 [95% CI, 0.79-0.96]) and TICI 2c/3 (aOR, 0.87 [95% CI, 0.79-0.95]) per hour ATG delay, while the reduction of TICI 2b-3 per hour increase symptom-onset-to-admission was minor (aOR, 0.97 [95% CI, 0.94-0.99]) and inconsistent regarding TICI 2c/3 (aOR, 0.99 [95% CI, 0.97-1.02]). After adjusting for identified factors associated with prolonged ATG intervals, the association of ATG delay and lower rates of TICI 2b-3 remained tangible (aOR, 0.87 [95% CI, 0.76-0.99]). There is a great potential to reduce ATG, and potential targets for improvement can be deduced from observational data. The association between in-hospital delay and reduced reperfusion rates is evident in real-world clinical data, underscoring the need to optimize in-hospital workflows. Given the only minor association between symptom-onset-to-admission intervals and reperfusion rates, the causal relationship of this association warrants further research. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496064

Enhancing Education to Avoid Complications in Endovascular Treatment of Unruptured Intracranial Aneurysms: A Neurointerventionalist's Perspective

It is of utmost importance to avoid errors and subsequent complications when performing neurointerventional procedures, particularly when treating low-risk conditions such as unruptured intracranial aneurysms. We used endovascular treatment of unruptured intracranial aneurysms as an example and took a survey-based approach in which we reached out to 233 neurointerventionalists. They were asked what they think are the most important points staff should teach their trainees to avoid errors and subsequent complications in endovascular treatment of unruptured intracranial aneurysms. One hundred twenty-one respondents (51.9%) provided answers in the form of free text responses, which were thematically clustered in an affinity diagram and summarized in this Practice Perspectives. The article is primarily intended for neurointerventional radiology fellows and junior staff and will hopefully provide them the opportunity to learn from the mistakes of their more experienced colleagues

A DELPHI consensus statement on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of mechanical thrombectomy

Purpose There is little data and lack of consensus regarding antiplatelet management for intracranial stenting due to underlying intracranial atherosclerosis in the setting of endovascular treatment (EVT). In this DELPHI study, we aimed to assess whether consensus on antiplatelet management in this situation among experienced experts can be achieved, and what this consensus would be. Methods We used a modified DELPHI approach to address unanswered questions in antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. An expert-panel (19 neurointerventionalists from 8 countries) answered structured, anonymized on-line questionnaires with iterative feedback-loops. Panel-consensus was defined as agreement >= 70% for binary closed-ended questions/>= 50% for closed-ended questions with > 2 response options. Results Panel members answered a total of 5 survey rounds. They acknowledged that there is insufficient data for evidence-based recommendations in many aspects of antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. They believed that antiplatelet management should follow a standardized regimen, irrespective of imaging findings and reperfusion quality. There was no consensus on the timing of antiplatelet-therapy initiation. Aspirin was the preferred antiplatelet agent for the peri-procedural period, and oral Aspirin in combination with a P2Y12 inhibitor was the favored postprocedural regimen. Conclusion Data on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT are limited. Panel-members in this study achieved consensus on postprocedural antiplatelet management but did not agree upon a preprocedural and intraprocedural antiplatelet regimen. Further prospective studies to optimize antiplatelet regimens are needed.Neuro Imaging Researc

Clinical outcome of patients with mild pre-stroke morbidity following endovascular treatment: a HERMES substudy

Background: Analyses of the effect of pre-stroke functional levels on the outcome of endovascular therapy (EVT) have focused on the course of patients with moderate to substantial pre-stroke disability. The effect of complete freedom from pre-existing disability (modified Rankin Scale (mRS) 0) versus predominantly mild pre-existing disability/symptoms (mRS 1-2) has not been well delineated. Methods: The HERMES meta-analysis pooled data from seven randomized trials that tested the efficacy of EVT. We tested for a multiplicative interaction effect of pre-stroke mRS on the relationship between treatment and outcomes. Ordinal regression was used to assess the association between EVT and 90-day mRS (primary outcome) in the subgroup of patients with pre-stroke mRS 1-2. Multivariable regression modeling was then used to test the effect of mild pre-stroke disability/symptoms on the primary and secondary outcomes (delta-mRS, mRS 0-2/5-6) compared with patients with pre-stroke mRS 0. Results: We included 1764 patients, of whom 199 (11.3%) had pre-stroke mRS 1-2. No interaction effect of pre-stroke mRS on the relationship between treatment and outcome was observed. Patients with pre-stroke mRS 1-2 had worse outcomes than those with pre-stroke mRS 0 (adjusted common OR (acOR) 0.53, 95% CI 0.40 to 0.70). Nonetheless, a significant benefit of EVT was observed within the mRS 1-2 subgroup (cOR 2.08, 95% CI 1.22 to 3.55). Conclusions: Patients asymptomatic/without disability prior to onset have better outcomes following EVT than patients with mild disability/symptoms. Patients with pre-stroke mRS 1-2, however, more often achieve good outcomes with EVT compared with conservative management. These findings indicate that mild pre-existing disability/symptoms influence patient prognosis after EVT but do not diminish the EVT treatment effect.</p

Combined Effect of Age and Baseline Alberta Stroke Program Early Computed Tomography Score on Post-Thrombectomy Clinical Outcomes in the MR CLEAN Registry

BACKGROUND AND PURPOSE: Ischemic brain tissue damage in patients with acute ischemic stroke, as measured by the Alberta Stroke Program Early CT Score (ASPECTS) may be more impactful in older than in younger patients, although this has not been studied. We aimed to investigate a possible interaction effect between age and ASPECTS on functional outcome in acute ischemic stroke patients undergoing endovascular treatment, and compared reperfusion benefit across age and ASPECTS subgroups. METHODS: Patients with ischemic stroke from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; March 2014-November 2017) were included. Multivariable ordinal logistic regression was performed to obtain effect size estimates (adjusted common odds ratio) on functional outcome (modified Rankin Scale score) for continuous age and granular ASPECTS, with a 2-way multiplicative interaction term (agexASPECTS). Outcomes in four patient subgroups based on age (/= median age [71.8 years]) and baseline ASPECTS (6-10 versus 0-5) were assessed. RESULTS: We included 3279 patients. There was no interaction between age and ASPECTS on modified Rankin Scale (P=0.925). The highest proportion of modified Rankin Scale 5 to 6 was observed in patients >71.8 years with baseline ASPECTS 0 to 5 (68/107, 63.6%). There was benefit of reperfusion in all age-ASPECTS subgroups. Although the adjusted common odds ratio was lower in patients >71.8 years with ASPECTS 0 to 5 (adjusted common odds ratio, 1.60 [95% CI, 0.66-3.88], n=110), there was no significant difference from the main effect (P=0.299). CONCLUSIONS: Although the proportion of poor outcomes following endovascular treatment was highest in older patients with low baseline ASPECTS, outcomes did not significantly differ from the main effect. These results do not support withholding endovascular treatment based n a combination of high age and low ASPECTS

Global impact of COVID-19 on stroke care

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March–31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, −19.7 to −18.7), 11.5% (95%CI, −12.6 to −10.6), and 12.7% (95%CI, −13.6 to −11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (−20.5%) had greater declines in mechanical thrombectomy volumes than mid- (−10.1%) and low-volume (−8.7%) centers (p &lt; 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes. © 2021 World Stroke Organization