Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

Hemodynamic Stroke: Emerging Concepts, Risk Estimation, and Treatment.

Ischemic stroke can arise from the sudden occlusion of a brain-feeding artery by a clot (embolic), or local thrombosis. Hemodynamic stroke occurs when blood flow does not sufficiently meet the metabolic demand of a brain region at a certain time. This discrepancy between demand and supply can occur with cerebropetal arterial occlusion or high-grade stenosis but also arises with systemic conditions reducing blood pressure. Treatment of hemodynamic stroke is targeted toward increasing blood flow to the affected area by either systemically or locally enhancing perfusion. Thus, blood pressure is often maintained above normal values, and extra-intracranial flow augmentation bypass surgery is increasingly considered. Still, current evidence supporting the superiority of pressure or flow increase over conservative measures is limited. However, methods assessing hemodynamic impairment and identifying patients at risk of hemodynamic stroke are rapidly evolving. Sophisticated models incorporating clinical and imaging factors have been suggested to aid patient selection. In this narrative review, we provide current state-of-the-art knowledge about hemodynamic stroke, tools for assessment, and treatment options.

Emergent Large Vessel Occlusion due to Intracranial Stenosis: Identification, Management, Challenges, and Future Directions.

This comprehensive literature review focuses on acute stroke related to intracranial atherosclerotic stenosis (ICAS), with an emphasis on ICAS-large vessel occlusion. ICAS is the leading cause of stroke globally, with high recurrence risk, especially in Asian, Black, and Hispanic populations. Various risk factors, including hypertension, diabetes, hyperlipidemia, smoking, and advanced age lead to ICAS, which in turn results in stroke through different mechanisms. Recurrent stroke risk in patients with ICAS with hemodynamic failure is particularly high, even with aggressive medical management. Developments in advanced imaging have improved our understanding of ICAS and ability to identify high-risk patients who could benefit from intervention. Herein, we focus on current management strategies for ICAS-large vessel occlusion discussed, including the use of perfusion imaging, endovascular therapy, and stenting. In addition, we focus on strategies that aim at identifying subjects at higher risk for early recurrent risk who could benefit from early endovascular intervention The review underscores the need for further research to optimize ICAS-large vessel occlusion treatment strategies, a traditionally understudied topic.

Addressing the Evidence Gap in Aneurysmal Subarachnoid Hemorrhage: The Need for a Pragmatic Randomized Trial Platform.

Aneurysmal subarachnoid hemorrhage (aSAH) occurs less often than other stroke types but affects younger patients, imposing a disproportionately high burden of long-term disability. Although management advances have improved outcomes over time, relatively few aSAH treatments have been tested in randomized clinical trials (RCTs). One lesson learned from COVID-19 is that trial platforms can facilitate the efficient execution of multicenter RCTs even in complex diseases during challenging conditions. An aSAH trial platform with standardized eligibility criteria, randomization procedures, and end point definitions would enable the study of multiple targeted interventions in a perpetual manner, with treatments entering and leaving the platform based on predefined decision algorithms. An umbrella institutional review board protocol and clinical trial agreement would allow individual arms to be efficiently added as amendments rather than stand-alone protocols. Standardized case report forms using the National Institutes of Health/National Institute of Neurological Disorders and Stroke common data elements and general protocol standardization across arms would create synergies for data management and monitoring. A Bayesian analysis framework would emphasize frequent interim looks to enable early termination of trial arms for futility, common controls, borrowing of information across arms, and adaptive designs. A protocol development committee would assist investigators and encourage pragmatic designs to maximize generalizability, reduce site burden, and execute trials efficiently and cost-effectively. Despite decades of steady clinical progress in the management of aSAH, poor patient outcomes remain common, and despite the increasing availability of RCT data in other fields, it remains difficult to perform RCTs to guide more effective care for aSAH. The development of a platform for pragmatic RCTs in aSAH would help close the evidence gap between aSAH and other stroke types and improve outcomes for this important disease with its disproportionate public health burden.

Transcarotid Arterial Revascularization of Symptomatic Internal Carotid Artery Disease: A Systematic Review and Study-Level Meta-Analysis.

BACKGROUND: Transcarotid artery revascularization (TCAR) is an interventional therapy for symptomatic internal carotid artery disease. Currently, the utilization of TCAR is contentious due to limited evidence. In this study, we evaluate the safety and efficacy of TCAR in patients with symptomatic internal carotid artery disease compared with carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: A systematic review was conducted, spanning from January 2000 to February 2023, encompassing studies that used TCAR for the treatment of symptomatic internal carotid artery disease. The primary outcomes included a 30-day stroke or transient ischemic attack, myocardial infarction, and mortality. Secondary outcomes comprised cranial nerve injury and major bleeding. Pooled odds ratios (ORs) for each outcome were calculated to compare TCAR with CEA and CAS. Furthermore, subgroup analyses were performed based on age and degree of stenosis. In addition, a sensitivity analysis was conducted by excluding the vascular quality initiative registry population. RESULTS: A total of 7 studies involving 24 246 patients were analyzed. Within this patient cohort, 4771 individuals underwent TCAR, 12 350 underwent CEA, and 7125 patients underwent CAS. Compared with CAS, TCAR was associated with a similar rate of stroke or transient ischemic attack (OR, 0.77 [95% CI, 0.33-1.82]) and myocardial infarction (OR, 1.29 [95% CI, 0.83-2.01]) but lower mortality (OR, 0.42 [95% CI, 0.22-0.81]). Compared with CEA, TCAR was associated with a higher rate of stroke or transient ischemic attack (OR, 1.26 [95% CI, 1.03-1.54]) but similar rates of myocardial infarction (OR, 0.9 [95% CI, 0.64-1.38]) and mortality (OR, 1.35 [95% CI, 0.87-2.10]). CONCLUSIONS: Although CEA has traditionally been considered superior to stenting for symptomatic carotid stenosis, TCAR may have some advantages over CAS. Prospective randomized trials comparing the 3 modalities are needed.

Dural arteriovenous fistulas are not observed to convert to a higher grade after partial embolization.

OBJECTIVE: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

Recruitment in Acute Stroke Trials: Challenges and Potential Solutions.

Randomized clinical trials of acute stroke have led to major advances in acute stroke therapy over the past decade. Despite these successes, recruitment in acute trials is often difficult. We outline challenges in recruitment for acute stroke trials and present potential solutions, which can increase the speed and decrease the cost of identifying new treatments for acute stroke. One of the largest opportunities to increase the speed of enrollment and make trials more generalizable is expansion of inclusion criteria whose impact on expected recruitment can be assessed by epidemiologic and registry databases. Another barrier to recruitment besides the number of eligible patients is availability of study investigators limited to business hours, which may be helped by financial support for after-hours call. The wider use of telemedicine has accelerated quicker stroke treatment at many hospitals and has the potential to accelerate research enrollment but requires training of clinical investigators who are often inexperienced with this approach. Other potential solutions to enhance recruitment include rapid prehospital notification of clinical investigators of potential patients, use of mobile stroke units, advances in the process of emergency informed consent, storage of study medication in the emergency department, simplification of study treatments and data collection, education of physicians to improve equipoise and enthusiasm for randomization of patients within a trial, and clear recruitment plans, and even potentially coenrollment, when there are competing trials at sites. Without successful recruitment, scientific advances and clinical benefit for acute stroke patients will lag.

Large Vessel Occlusion Stroke due to Intracranial Atherosclerotic Disease: Identification, Medical and Interventional Treatment, and Outcomes.

Large vessel occlusion stroke due to underlying intracranial atherosclerotic disease (ICAD-LVO) is prevalent in 10 to 30% of LVOs depending on patient factors such as vascular risk factors, race and ethnicity, and age. Patients with ICAD-LVO derive similar functional outcome benefit from endovascular thrombectomy as other mechanisms of LVO, but up to half of ICAD-LVO patients reocclude after revascularization. Therefore, early identification and treatment planning for ICAD-LVO are important given the unique considerations before, during, and after endovascular thrombectomy. In this review of ICAD-LVO, we propose a multistep approach to ICAD-LVO identification, pretreatment and endovascular thrombectomy considerations, adjunctive medications, and medical management. There have been no large-scale randomized controlled trials dedicated to studying ICAD-LVO, therefore this review focuses on observational studies.

2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

AIM: The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage. METHODS: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

Perioperative Neurological Evaluation and Management to Lower the Risk of Acute Stroke in Patients Undergoing Noncardiac, Nonneurological Surgery: A Scientific Statement From the American Heart Association/American Stroke Association.

Perioperative stroke is a potentially devastating complication in patients undergoing noncardiac, nonneurological surgery. This scientific statement summarizes established risk factors for perioperative stroke, preoperative and intraoperative strategies to mitigate the risk of stroke, suggestions for postoperative assessments, and treatment approaches for minimizing permanent neurological dysfunction in patients who experience a perioperative stroke. The first section focuses on preoperative optimization, including the role of preoperative carotid revascularization in patients with high-grade carotid stenosis and delaying surgery in patients with recent strokes. The second section reviews intraoperative strategies to reduce the risk of stroke, focusing on blood pressure control, perioperative goal-directed therapy, blood transfusion, and anesthetic technique. Finally, this statement presents strategies for the evaluation and treatment of patients with suspected postoperative strokes and, in particular, highlights the value of rapid recognition of strokes and the early use of intravenous thrombolysis and mechanical embolectomy in appropriate patients.

Risk of Early Versus Later Rebleeding From Dural Arteriovenous Fistulas With Cortical Venous Drainage.

BACKGROUND: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage. METHODS: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference. RESULTS: Of 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2-14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3-5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7-12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4-37.7; P, 0.026). CONCLUSIONS: The risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.

Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis: The CASSISS Randomized Clinical Trial.

Importance: Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes. Objective: To compare stenting plus medical therapy vs medical therapy alone in patients with symptomatic severe intracranial atherosclerotic stenosis. Design, Setting, and Participants: Multicenter, open-label, randomized, outcome assessor-blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non-basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years (final follow-up: November 10, 2019). Interventions: Medical therapy plus stenting (n = 176) or medical therapy alone (n = 182). Medical therapy included dual-antiplatelet therapy for 90 days (single antiplatelet therapy thereafter) and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. There were 5 secondary outcomes, including stroke in the qualifying artery territory at 2 years and 3 years as well as mortality at 3 years. Results: Among 380 patients who were randomized, 358 were confirmed eligible (mean age, 56.3 years; 263 male [73.5%]) and 343 (95.8%) completed the trial. For the stenting plus medical therapy group vs medical therapy alone, no significant difference was found for the primary outcome of risk of stroke or death (8.0% [14/176] vs 7.2% [13/181]; difference, 0.4% [95% CI, -5.0% to 5.9%]; hazard ratio, 1.10 [95% CI, 0.52-2.35]; P = .82). Of the 5 prespecified secondary end points, none showed a significant difference including stroke in the qualifying artery territory at 2 years (9.9% [17/171] vs 9.0% [16/178]; difference, 0.7% [95% CI, -5.4% to 6.7%]; hazard ratio, 1.10 [95% CI, 0.56-2.16]; P = .80) and 3 years (11.3% [19/168] vs 11.2% [19/170]; difference, -0.2% [95% CI, -7.0% to 6.5%]; hazard ratio, 1.00 [95% CI, 0.53-1.90]; P > .99). Mortality at 3 years was 4.4% (7/160) in the stenting plus medical therapy group vs 1.3% (2/159) in the medical therapy alone group (difference, 3.2% [95% CI, -0.5% to 6.9%]; hazard ratio, 3.75 [95% CI, 0.77-18.13]; P = .08). Conclusions and Relevance: Among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The findings do not support the addition of percutaneous transluminal angioplasty and stenting to medical therapy for the treatment of patients with symptomatic severe intracranial atherosclerotic stenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT01763320.

Image level detection of large vessel occlusion on 4D-CTA perfusion data using deep learning in acute stroke.

OBJECTIVES: Automated image-level detection of large vessel occlusions (LVO) could expedite patient triage for mechanical thrombectomy. A few studies have previously attempted LVO detection using artificial intelligence (AI) on CT angiography (CTA) images. To our knowledge this is the first study to detect LVO existence and location on raw 4D-CTA/ CT perfusion (CTP) images using neural network (NN) models. MATERIALS AND METHODS: Retrospective study using data from a level-I stroke center was performed. A total of 306 (187 with LVO, and 119 without) patients were evaluated. Image pre-processing included co-registration, normalization and skull stripping. Five consecutive time-points for each patient were selected to provide variable contrast density in data. Additional data augmentation included rotation and horizonal image flipping. Our model architecture consisted of two neural networks, first for classification (based on hemispheric asymmetry), followed by second model for exact site of LVO detection. Only cases deemed positive by the classification model were routed to the detection model, thereby reducing false positives and improving specificity. The results were compared with expert annotated LVO detection. RESULTS: Using a 80:20 split for training and validation, the combination of both classification and detection model achieved a sensitivity of 86.5%, a specificity of 89.5%, and an accuracy of 87.5%. A 5-fold cross-validation using the entire data achieved a mean sensitivity of 82.7%, a specificity of 89.8%, and an accuracy of 85.5% and a mean AUC of 0.89 (95% CI: 0.85-0.93). CONCLUSION: Our findings suggest that accurate image-level LVO detection is feasible on CTP raw images.

CT Perfusion Maps Improve Detection of M2-MCA Occlusions in Acute Ischemic Stroke.

OBJECTIVES: Middle cerebral artery occlusions, particularly M2 branch occlusions are challenging to identify on CTA. We hypothesized that additional review of the CTP maps will increase large vessel occlusion (LVO) detection accuracy on CTA and reduce interpretation time. MATERIALS AND METHODS: Two readers (R1 and R2) retrospectively reviewed the CT studies in 99 patients (27 normal, 26 M1-MCA, 46 M2-MCA occlusions) who presented with suspected acute ischemic stroke (AIS). The time of interpretation and final diagnosis were recorded for the CTA images (derived from CTP data), both without and with the CTP maps. The time for analysis for all vascular occlusions was compared using McNemar tests. ROC curve analysis and McNemar tests were performed to assess changes in diagnostic performance with the addition of CTP maps. RESULTS: With the addition of the CTP maps, both readers showed increased sensitivity (p = 0.01 for R1 and p = 0.04 for R2), and accuracy (p = 0.02 for R1 and p = 0.004 for R2) for M2-MCA occlusions. There was a significant improvement in diagnostic performance for both readers for detection of M2-MCA occlusions (AUC R1 = 0.86 to 0.95, R2 = 0.84 to 0.95; p < 0.05). Both readers showed reduced interpretation time for all cases combined, as well as for normal studies (p < 0.001) when CTP images were reviewed along with CTA. Both readers also showed reduced interpretation time for M2-MCA occlusions, which was significant for one of the readers (p < 0.02). CONCLUSION: The addition of CTP maps improves accuracy and reduces interpretation time for detecting LVO and M2-MCA occlusions in AIS. Incorporation of CTP in acute stroke imaging protocols may improve detection of more distal occlusions.

Acute Stroke Imaging Research Roadmap IV: Imaging Selection and Outcomes in Acute Stroke Clinical Trials and Practice.

BACKGROUND AND PURPOSE: The Stroke Treatment Academic Industry Roundtable (STAIR) sponsored an imaging session and workshop during the Stroke Treatment Academic Industry Roundtable XI via webinar on October 1 to 2, 2020, to develop consensus recommendations, particularly regarding optimal imaging at primary stroke centers. METHODS: This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss imaging priorities in the light of developments in reperfusion therapies, particularly in an extended time window, and reinvigorated interest in brain cytoprotection trials. RESULTS: The imaging session summarized and compared the imaging components of recent acute stroke trials and debated the optimal imaging strategy at primary stroke centers. The imaging workshop developed consensus recommendations for optimizing the acquisition, analysis, and interpretation of computed tomography and magnetic resonance acute stroke imaging, and also recommendations on imaging strategies for primary stroke centers. CONCLUSIONS: Recent positive acute stroke clinical trials have extended the treatment window for reperfusion therapies using imaging selection. Achieving rapid and high-quality stroke imaging is therefore critical at both primary and comprehensive stroke centers. Recommendations for enhancing stroke imaging research are provided.

Natural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort.

BACKGROUND AND PURPOSE: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. METHODS: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. RESULTS: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7]). CONCLUSIONS: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980.

Differential Risk Factors and Outcomes of Ischemic Stroke due to Cervical Artery Dissection in Young Adults.

INTRODUCTION: Cervical artery dissection (CeAD) is a major cause of ischemic stroke in young adults. Our understanding of the specific risk factors and clinical course of CeAD is still evolving. In this study, we evaluated the differential risk factors and outcomes of CeAD-related strokes among young adults. METHODS: The study population consisted of young patients 15-45 years of age consecutively admitted with acute ischemic stroke to our comprehensive stroke center between January 1, 2010, and November 30, 2016. Diagnosis of CeAD was based on clinical and radiological findings. Univariate and multivariable logistic regression analyses were used to assess the risk factors and clinical outcomes associated with CeAD-related strokes. RESULTS: Of the total 333 patients with acute ischemic stroke included in the study (mean ± SD age: 36.4 ± 7.1 years; women 50.8%), CeAD was identified in 79 (23.7%) patients. As compared to stroke due to other etiologies, patients with CeAD were younger in age, more likely to have history of migraine and recent neck manipulation and were less likely to have hypertension, diabetes, and previous history of stroke. Clinical outcomes of CeAD were comparable to strokes due to other etiologies. Within the CeAD group, higher initial stroke severity and history of tobacco use were associated with higher modified Rankin Scale score at follow-up. CONCLUSIONS: While history of migraine and neck manipulation are significantly associated with CeAD, most of the traditional vascular risk factors for stroke are less prevalent in this group when compared to strokes due to other etiologies. For CeAD-related strokes, higher initial stroke severity and history of tobacco use may be associated with higher stroke-related disability, but overall, patients with CeAD have similar outcomes as compared to strokes due to other etiologies.

Cerebral computed tomographic angiography using third-generation reconstruction algorithm provides improved image quality with lower contrast and radiation dose.

PURPOSE: We hypothesized that cerebral CT angiogram performed using third-generation reconstruction algorithm and lower contrast dose-low-kVp technique (LD-CTA) will provide better image quality when compared with regular contrast dose CTA at 120 kVp using a sinogram-affirmed iterative reconstruction algorithm (ND-CTA). METHODS: Retrospective imaging review of 100 consecutive patients (50 each in LD- and ND-CTA groups). Two readers independently assessed the subjective image quality across multiple vascular segments on a Likert-like scale. Differences in contrast dose, CT dose index (CTDI), and dose length product (DLP) were compared using Mann-Whitney U test. Fisher's exact test was used to compare subjective image quality. Similarly, contrast- and signal-to-noise ratios (CNR and SNR) were compared in the mid-M1 MCA vessels bilaterally and the mid-basilar artery using Mann-Whitney U test. Interclass correlation coefficient (ICC) was calculated for the SNR/CNR values. RESULTS: Both observers showed excellent correlation in subjective image quality (mean percentage agreement of 95.2% for group 1 versus 89.2% for group 2). LD-CTA group showed better SNR and CNR (p < 0.0001) for both MCA vessels and the mid-basilar artery. Interclass correlation coefficient showed moderate correlation (0.51-0.63) between readers. LD-CTA group also used lower contrast (49 cc versus 97 cc in ND-CTA) and had lower radiation exposure (DLP/CTDI for both groups 268.3/80.7 vs 519.5/36.08, both < 0.0001). CONCLUSION: Next-generation reconstruction algorithm and low-kV scanning significantly improved image quality on cerebral CTA images despite lower contrast dose and, in addition, have lower radiation exposure.

In-House Anesthesia and Interventional Radiology Technologist Support Optimize Mechanical Thrombectomy Workflow after Hours.

BACKGROUND AND PURPOSE: Prior literature suggests after-hours delay leads to poor functional outcomes in stroke patients undergoing thrombectomy. We aimed to evaluate the impact of time of presentation on mechanical thrombectomy (MT) metrics and its association with long-term functional outcome in an Interventional Radiology (IR) suite equipped operating room (OR) setting. METHODS: Retrospective review of prospectively maintained database on all stroke patients undergoing mechanical thrombectomy between January 2015 and December 2018 at our CSC. Work hours were defined by official OR work hours (Monday-Friday 7 AM and 5 PM) and after-hours as between 5 PM and 7 AM during weekdays and weekends as well as official hospital holidays. Primary outcome was 90-day modified Rankin Scale (mRS). Secondary outcomes included door to groin puncture time and procedural complications. RESULTS: A total of 315 patients were included in the analyses. 209 (66.4%) received mechanical thrombectomy after hours and 106 (33.6%) during work hours. There was no difference in the shift distribution of functional outcome on the mRS at 90 days (OR: 1.14, CI: 0.72-1.78, p=0.58) and the percentage of patients achieving functional independence (mRS 0-2) at 90 days (43.1% vs. 41.3%; p=0.83) between the after hour and work hour groups respectively. Similarly, there was no difference in median door to groin times and procedural complications among both groups, with significant year on year improvement in overall time metrics. CONCLUSIONS: Our study showed that undergoing MT during off-hours had similar functional outcomes when compared to MT during working hours in an OR setting. The after-hours deleterious effect might disappear when MT is performed in a system with 24-hours in-house Anesthesia and IR tech services.