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Background and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P

Background Acute ischemic stroke arising from medium vessel occlusions (MeVO) poses substantial challenges in treatment and management. This study aims to elucidate the outcomes and factors contributing to achieving excellent recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3) versus successful recanalization (mTICI 2b) in patients with MeVO stroke undergoing mechanical thrombectomy (MT). Methods We conducted a multinational study analyzing data from the MAD‐MT (Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy) registry, encompassing 37 centers across North America, Asia, and Europe, collected between September 2017 and July 2023. The study included acute ischemic stroke patients with MeVO treated with MT, with or without intravenous thrombolysis, who achieved mTICI 2b–3 post‐MT. Results Among 1463 patients with successful recanalization (mTICI 2b–3), 523 achieved mTICI 2b recanalization, and 940 achieved mTICI 2c–3. Distal occlusions exhibited higher odds of excellent recanalization compared with proximal MeVO vessel occlusions (odds ratio, 1.58; 95% CI, 1.17–2.15; P = 0.003). Cardioembolic stroke pathogenesis was associated with a higher likelihood of excellent recanalization (1.67; 95% CI, 1.07–2.59; P = 0.018). Patients achieving mTICI 2c–3 recanalization demonstrated lower initial National Institutes of Health Stroke Scale scores, significant improvements in postprocedural National Institutes of Health Stroke Scale shift, and a higher percentage of favorable 90‐day outcomes compared with those with mTICI 2b. However, no significant difference in 90‐day mortality rates was observed. Conclusion This study underscores that among patients with MeVO stroke with successful recanalization (mTICI 2b–3) there is higher likelihood of achieving excellent recanalization (mTICI 2c–3) in distal occlusions and cardioembolic pathogenesis. mTICI 2c–3 scores post‐MT correlate with improved clinical outcomes compared with mTICI 2b, affirming the superiority of excellent recanalization over successful recanalization in patients with MeVO stroke. Further prospective studies and randomized controlled trials are warranted for validation.

Background Mechanical thrombectomy has changed the landscape of acute ischemic stroke treatment, offering improved outcomes for patients with large vessel occlusions. The interplay between reperfusion techniques and occlusion sites remains a critical consideration in treatment decisions. This study investigates the impact of primary reperfusion techniques—stent retriever classic, stent retriever combination with aspiration, and direct aspiration—on procedural and clinical outcomes at different occlusion sites. Methods Using data from the ASSIST registry, a prospective multinational initiative, patients with anterior circulation acute ischemic stroke with large vessel occlusions (n = 1477) were included. Three primary occlusion sites—M1 segment of the middle cerebral artery, M2 segment of the middle cerebral artery, and the internal carotid artery—were studied. Univariate tests and multivariable logistic regression models were used to assess associations between reperfusion techniques and procedural and clinical outcomes, including the expanded thrombolysis in cerebral infarction score and the modified Rankin Scale, stratified by occlusion site. Results Achieving expanded thrombolysis in cerebral infarction ≥2c after first pass was lower in internal carotid artery occlusions (18.2%, P

Intracranial atherosclerosis is a leading cause of stroke with a high recurrence rate despite treatment. Numerous factors are proposed to influence stroke recurrence due to intracranial atherosclerosis including lesion eccentricity, plaque characteristics, and computational fluid dynamic metrics, such as wall shear stress. An overlooked variable that intrinsically relates to intracranial atherosclerosis is the location of the arterial segment where the lesion occurs. Variations in cerebral blood flow, arterial anatomy, and flow dynamics are likely drivers of initial lesion development and thus likely to influence stroke recurrence. To date, treatment trials of intracranial atherosclerosis have not considered arterial segment lesion location as an independent variable, failing to account for variations in flow dynamics between each artery. There are limited available data on differences between arterial segments, confined to only post hoc analyses. In this review, we summarize available data on such differences between arterial segments. With the limited arterial segment data available, multiple differences in recurrence of stroke in territory of lesion were identified across trials.

Abstract The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09–1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22–1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS.

BackgroundThe extent of ischemic injury in acute stroke is assessed in clinical practice using the Acute Stroke Prognosis Early CT Score (ASPECTS) rating system. However, current ASPECTS semi-quantitative topographic scales assess only the middle cerebral artery (MCA) (original ASPECTS) and posterior cerebral (PC-ASPECTS) territories. For treatment decision-making in patients with anterior cerebral artery (ACA) occlusions and internal carotid artery (ICA) occlusions with large ischemic cores, measures of all hemispheric regions are desirable.MethodsIn this cohort study, anatomic rating systems were developed for the anterior cerebral (AC-ASPECTS, 3 points) and anterior choroidal artery (ACh-ASPECTS, 1 point) territories. In addition, a total supratentorial hemisphere (H-ASPECTS, 16 points) score was calculated as the sum of the MCA ASPECTS (10 regions), supratentorial PC-ASPECTS (2 regions), AC-ASPECTS (3 regions), and ACh-ASPECTS (1 region). Three raters applied these scales to initial and 24 h CT and MR images in consecutive patients with ischemic stroke (IS) due to ICA, M1-MCA, and ACA occlusions.ResultsImaging ratings were obtained for 96 scans in 50 consecutive patients with age 74.8 (±14.0), 60% female, NIHSS 15.5 (9.25–20), and occlusion locations ICA 34%; M1-MCA 58%; and ACA 8%. Treatments included endovascular thrombectomy +/− thrombolysis in 72%, thrombolysis alone in 8%, and hemicraniectomy in 4%. Among experienced clinicians, inter-rater reliability for AC-, ACh-, and H-ASPECTS scores was substantial (kappa values 0.61–0.80). AC-ASPECTS abnormality was present in 14% of patients, and ACh-ASPECTS abnormality in 2%. Among patients with ACA and ICA occlusions, H-ASPECTS scores compared with original ASPECTS scores were more strongly associated with disability level at discharge, ambulatory status at discharge, discharge destination, and combined inpatient mortality and hospice discharge.ConclusionAC-ASPECTS, ACh-ASPECTS, and H-ASPECTS expand the scope of acute IS imaging scores and increase correlation with functional outcomes. This additional information may enhance prognostication and decision-making, including endovascular thrombectomy and hemicraniectomy.

Background PP‐007 is a polyethylene glycol (PEG)ylated bovine carboxyhemoglobin gas transfer molecule with pleotropic cytoprotective effects, vasodilatation, plasma expansion, and optimization of oxygen delivery. Rodent middle cerebral artery occlusion models have demonstrated that PP‐007 increases blood flow in the collateral circulation and reduces final infarct volumes, supporting a potential role as neuroprotective agent in acute ischemic stroke. We aim to evaluate the safety and feasibility of PP‐007 as an adjunctive treatment to mechanical thrombectomy (MT) in patients with stroke secondary to large vessel occlusion. Methods HEMERA‐1 (CarboxyHEMoglobin OxygEn delivery for Revascularization in Acute Stroke) was a multicenter, prospective, randomized, controlled phase 1 clinical trial. Anterior circulation large vessel occlusion patients were assigned in a 3:1 ratio to receive either PP‐007 (320 mg/kg: 30 min bolus followed by 2‐h infusion) plus MT or MT alone within 24 hours after symptom onset. Comprehensive safety evaluation was performed by independent Data Monitoring Safety Board and Imaging Core Lab. Results From October 1, 2021 to June 30, 2022, a total of 17 patients were recruited. Age, baseline National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT Score were 74.8±12.7 years, 17.3±4.2, and 7.9±1.8, respectively. Twelve patients were randomized to PP‐007 plus MT, 1 was randomized but not treated, 4 patients were randomized to MT alone. Recanalization of the occluded vessel was achieved in all patients. A transient systolic blood pressure increase (20–40 mm Hg) during the bolus was observed in all PP‐007 patients without any clinical consequences. There were no other safety concerns. Conclusion No significant safety concerns were identified for the adjunctive use of PP‐007 in patients undergoing MT. (The study was funded by Prolong Pharmaceuticals. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04677777.

Background Stroke, a major global health issue, is broadly categorized into ischemic and hemorrhagic types. The volume of hemorrhage on noncontrast computed tomography guides the treatment options and hints at prognosis. Conventional approaches to calculate intracerebral hemorrhage (ICH) volume, like the ABC/2 method, typically rely on an assumed standard shape and might be inaccurate. Advances in deep learning have significantly improved noncontrast computed tomography's capabilities in ICH volume estimation. This study conducts a comprehensive systematic review and meta‐analysis to evaluate the precision of deep learning algorithms in delineating ICH on noncontrast computed tomography. Methods A systematic review and meta‐analysis, adhering to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, was conducted on literature from 2000 to October 2023. Studies were selected on the basis of strict inclusion and exclusion criteria. Performance evaluation was done using the Dice Similarity Coefficient, and the Prediction Model Risk of Bias Assessment Tool was used for quality assessment. Statistical analysis was carried out using Stata 17.0. Results The review included 28 studies, mainly retrospective cohorts, with a focus on convolutional neural network architectures, particularly U‐Net variants. A meta‐analysis of 14 studies revealed a combined Dice Similarity Coefficient of 0.85 (95% CI, 0.82–0.88). Performance was consistent across various methodologies but varied on the basis of ICH pathogenesis, with spontaneous ICH having higher accuracy. Conclusion Deep learning models are highly effective in segmenting ICH on noncontrast computed tomography, demonstrating potential improvements in clinical neuroimaging. Despite their efficacy, challenges in segmenting smaller hemorrhages remain. The findings suggest that deep learning could reduce health care professional workloads and enhance patient care, although further research is needed to address limitations and extend clinical utility.

Background Large‐vessel occlusion (LVO) ischemic stroke is responsible for significant morbidity and mortality. We have previously described a novel tool for acute LVO detection that combines blood‐based biomarkers (glial fibrillary acidic protein and d‐dimer) with stroke severity scales to achieve high accuracy. Accordingly, the present study sought to prospectively validate cutoff values that we had previously established for biomarkers and scales. Methods The TIME (Testing for Identification Markers of Stroke) trial was designed as a prospective observational diagnostic accuracy study. All ambulance‐identified stroke code activations

BackgroundValidating the National Institutes of Health NIH Stroke Scale (NIHSS) as a tool to assess deficit severity and prognosis in patients with acute intracerebral hemorrhage would harmonize the assessment of intracerebral hemorrhage (ICH) and acute ischemic stroke (AIS) patients, enable clinical use of a readily implementable and non-imaging dependent prognostic tool, and improve monitoring of ICH care quality in administrative datasets.MethodsAmong randomized trial ICH patients, the relation between NIHSS scores early after Emergency Department arrival and 3-month outcomes of dependency or death (modified Rankin Scale, mRS 3–6) and case fatality was examined. NIHSS predictive performance was compared to a current standard prognostic scale, the intracerebral hemorrhage score (ICH score).ResultsAmong the 384 patients, the mean age was 65 (±13), with 66% being male. The median NIHSS score was 16 (interquartile range (IQR) 9–25), the mean initial hematoma volume was 29 mL (±38), and the ICH score median was 1 (IQR 0–2). At 3 months, the mRS had a median of 4 (IQR 2–6), with dependency or death occurring in 70% and case fatality in 26%. The NIHSS and ICH scores were strongly correlated (r = 0.73), and each was strongly correlated with the 90-day mRS (NIHSS, r = 0.61; ICH score, r = 0.62). The NIHSS performed comparably to the ICH score in predicting both dependency or death (c = 0.80 vs. 0.80, p = 0.83) and case fatality (c = 0.78 vs. 0.80, p = 0.29). At threshold values, the NIHSS predicted dependency or death with 74.1% accuracy (NIHSS 17.5) and case fatality with 75.0% accuracy (NIHSS 18.5).ConclusionThe NIHSS forecasts 3-month functional and case fatality outcomes with accuracy comparable to the ICH Score. Widely documented in routine clinical care and administrative data, the NIHSS can serve as a valuable measure for clinical prognostication, therapy development, and case-mix risk adjustment in ICH patients.Clinical trial registrationClinicaltrials.gov, NCT00059332.

Summary: Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3–5 or infarct core volume 70–100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18–2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06–2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Background Mechanical thrombectomy is established for large‐vessel occlusions in acute ischemic stroke, but the potential role in distal vessel occlusions of medium arteries is less well established. Such medium or distal arterial segments have not been assessed with respect to thrombectomy devices used during endovascular therapy. We conducted an analysis of arterial size, segmental anatomy, and stent‐retriever device performance with respect to vessel size during thrombectomy. Methods The STRATIS registry angiography core laboratory adjudicated the exact location of the occlusion, proximal, and distal device deployment, relationship to arterial bifurcations, and anatomic nomenclature. Arterial diameters were measured at all these sites. Statistical analyses examined the relationship between vessel and stent size, and arterial recanalization using expanded Thrombolysis in Cerebral Infarction reperfusion score. Results Overall, 665 patients with stroke were included following thrombectomy using various Solitaire device sizes, including Solitaire 4×40, Solitaire 6×30, Solitaire 4×20, Solitaire 6×20, and Solitaire 4×15. Arterial diameter at the occlusion site was a median of 2.17 mm (interquartile range [IQR], 1.88–2.60 mm) in the distal M1, 1.67 mm (IQR, 1.47–2.06 mm) in the proximal M2 middle cerebral artery, 1.50 mm (IQR, 1.15–1.61 mm) in the distal M2 middle cerebral artery, 1.24 mm (IQR, 1.11–1.24 mm) in the M3 middle cerebral artery, and 1.88 mm (IQR, 1.49–1.94 mm) in the P1 posterior cerebral artery. Expanded Thrombolysis in Cerebral Infarction 2b to 3 reperfusion was achieved in all M3 or P1 segment occlusions. The rate of first‐pass recanalization was significantly higher in patients with medium (0.75–2 mm) versus large (>2 mm) vessel occlusion (69.5% versus 57.1%; P = 0.003). Conclusion Considerable overlap was noted between arterial sizes at occlusion sites carrying different segmental arterial nomenclature or vessel names. Substantial reperfusion may be achieved with currently available mechanical thrombectomy devices in medium arteries.

Background Subarachnoid hemorrhage (SAH) associated with vessel injury during endovascular therapy for acute ischemic stroke is a known complication. Arterial anatomy may predispose to increased risk of SAH and technical safety, yet factors such as clot location, arterial size, and tortuosity have not been explored. We examined these anatomic factors with respect to SAH during thrombectomy. Methods Arterial anatomy at the site of occlusion and mechanical thrombectomy during device deployment was detailed by the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) core laboratory. Luminal diameters, arterial branching, and segmental tortuosity were measured. Arterial tortuosity was quantified using the distance factor metric. Statistical analyses included descriptive variables of arterial anatomy, with univariable and multivariable modeling to predict SAH. Results Arterial tortuosity in each segment from the proximal cerebral arteries to the site of occlusion was quantified in 790 subjects treated with mechanical thrombectomy in STRATIS. Cumulative arterial tortuosity to the site of vessel occlusion was greater in distal lesions. SAH was clearly linked with more distal thrombectomy (P = 0.02), occurring in 19.0% of distal M2, 16.7% of M3, 7.3% of distal M1, 5.8% of proximal M2, 2.4% of distal internal carotid artery, and 2.1% of proximal M1. In multivariable analysis after adjusting for arterial diameter at the site of occlusion, arterial tortuosity was a significant predictor of SAH (upper tertile versus 1: odds ratio, 3.08 [95% CI, 1.04–9.09]; P = 0.04), while arterial diameter was unrelated to SAH (P = 0.30) when accounting for tortuosity. Conclusion This novel analysis of arterial tortuosity and angiographic anatomy during mechanical thrombectomy establishes tortuosity as a determinant of SAH, providing insight for future techniques and innovative device designs.

Background Early recognition of large‐vessel occlusion in acute ischemic stroke is pivotal to ensuring timely and effective treatment. However, current prehospital evaluation strategies largely rely on stroke scales that lack sensitivity and specificity. Recently, a novel, portable, noninvasive brain perfusion ultrasound device (SONAS) was developed as a diagnostic aid and demonstrated robust correlation with magnetic resonance imaging–based brain perfusion imaging. The present study aimed to investigate the feasibility and diagnostic performance of the SONAS device in identifying alterations in cerebral blood flow in patients with acute ischemic stroke with suspected or known perfusion deficits. Methods We performed a phase II, single‐arm, prospective study using SONAS in a close timely relation to computed tomography perfusion imaging in subjects diagnosed with acute ischemic stroke and suspected or known large‐vessel pathology, presenting within 24 hours of symptom onset between April 2019 through December 2019. Performance end points included successful measurement of time‐to‐peak in each hemisphere and comparison of perfusion deficits measured by SONAS to the reference standard computed tomography perfusion imaging. Safety end points included frequency, severity, and outcome of adverse events. Results A total of 20 subjects were enrolled. Eighteen subjects (90%) had microbubble signals successfully detected on initial assessment by SONAS. The diagnostic accuracy of the SONAS device in identifying a perfusion deficit was 88.9%. The sensitivity was 14 of 15 (93.3%), and the specificity was 2 of 3 (66.7%). No adverse events were reported secondary to SONAS or the contrast agent used. Conclusion In this clinical study, we demonstrated that the SONAS system is a safe tool that can aid in identifying cerebral perfusion deficits in this selected population of patients with acute ischemic stroke with suspected or known perfusion deficits. Future studies should assess the efficacy and impact on clinical outcomes of using SONAS in a real‐world “in the field” setting on a large subset of patients with suspected stroke and in addition to prehospital stroke scales.

The recent results of large core trials in acute ischemic stroke prompt the most influential paradigm shift in over a decade since endovascular therapy (EVT) was proven as the mainstay of acute stroke treatment. Six randomized, controlled trials (RCTs) of EVT in patients with more extensive ischemia on imaging than prior approved treatment indications revealed a consistent benefit of EVT, despite different imaging criteria and ischemic core definitions across the individual trials. These findings unfolded sequentially, akin to the acts of a drama, with the story evolving until perhaps the most conclusive results on extensive ischemia treatment about to be published. At this juncture, it is important to summarize the collective findings of these 6 RCTs, consider the potential expansion in the use of EVT, outline the penultimate or next steps during the encore of this drama and ponder the broad implications of these recent findings on the entire stroke field for many years to come. This logical rationale and perspective form the basis of Establishing Neuroimaging Criteria of Revascularization Efficacy (ENCORE), the proposed pooled, subject-level, meta-analysis of the recent large core trials, leveraging imaging re-adjudication by a collaborative, imaging core lab with documented expertise. Expansion of the treatment indications for EVT will likely ensue, yet numerous questions persist regarding other confounding variables that we normally use in routine clinical practice. Precision medicine for large core ischemic stroke mandates a more detailed investigation of the numerous clinical, imaging and angiographic variables that each trial dataset collected. In a simple pooled meta-analysis, these varying definitions, methodology and analytic approaches preclude anything beyond current summary results showing that EVT is favored, in general, over medical treatment. The epilog of the large core trials can be written by ENCORE, using the imaging and statistical methods and relevant expertise of the prior Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration.

IntroductionStroke interventions that increase collateral flow have the potential to salvage penumbral tissue and increase the number of patients eligible for reperfusion therapy. We compared the efficacy of two different collateral therapeutics during transient middle cerebral artery occlusion (tMCAO) in normotensive and hypertensive rats.MethodsThe change in collateral and core perfusion was measured using dual laser Doppler in response to either a pressor agent (phenylephrine, 10 mg/kg iv or vehicle) or a collateral vasodilator (TM5441, 5 mg/kg iv or vehicle) given 30 min into tMCAO in male Wistar and spontaneously hypertensive rats (SHRs).ResultsPressor therapy increased collateral flow in the Wistar rats but was ineffective in the SHRs. The increase in collateral flow in the Wistar rats was associated with impaired cerebral blood flow autoregulation (CBFAR) that was intact in the SHRs. TM5441 caused a decrease in collateral perfusion in the Wistar rats and a modest increase in the SHRs. The pressor therapy reduced early infarction in both groups but increased edema in the SHRs, whereas TM5441 did not have any beneficial effects in either group.ConclusionsThus, the pressor therapy was superior to a collateral vasodilator in increasing collateral flow and improving outcomes in the Wistar rats, likely due to pial collaterals that were pressure passive; the lack of CBF response in the SHRs to pressor therapy was likely due to intact CBFAR that limited perfusion. While TM5441 modestly increased CBF in the SHRs but not in the Wistar rats, it did not have a beneficial effect on stroke outcomes. These results suggest that collateral therapies may need to be selected for certain comorbidities.

Endovascular devices have catalyzed a global industry for advanced technologies such as flow diverters and stent retrievers. Though adoption of these devices has skyrocketed over the past 30 years, the regulatory landscape for real‐world monitoring is constantly under revision. Postmarket surveillance is an area of Medical Device Regulation that monitors how devices perform in the real world after regulatory approval. This area of research is underdeveloped globally, with most surveillance relying on passive adverse event data collection from health care systems. The US Food and Drug Administration has not yet established a comprehensive postmarket surveillance strategy for neuroendovascular devices. Postmarket clinical surveillance data are rare; only 4 mandated 522 postmarket neuroendovascular trials exist, and 4 of 14 endovascular registries have published results per ClinicalTrials.gov. The European Union 2017 Medical Device Regulation describes a comprehensive regulatory strategy to address postmarket surveillance, yet it has faced difficult implementation due to resource constraints and concerns such as increased costs and reliance on foreign devices and regulators. More than 50% of manufacturers are planning portfolio reductions, with 33% of the devices from these manufacturers planned for discontinuation. As of April 2022, >85% of 500 000+ previously certified devices were without new certification. In this article, we describe the current regulatory landscape for postmarket surveillance and support the need for a comprehensive, cost‐efficient postmarket strategy for neurovascular devices while proposing several solutions and considerations. An effective postmarket strategy has numerous benefits, such as promoting patient safety, expanding real‐world data collection, and increased efficiency for approving future devices.

Background Mechanical thrombectomy is an effective treatment method for large‐vessel occlusion stroke (LVOS); however, it has limited efficacy for intracranial atherosclerotic disease (ICAD)‐related LVOS. We investigated the use of cerebral blood volume (CBV) maps for identifying ICAD as the underlying cause of LVOS before the initiation of endovascular treatment (EVT). Methods and Results We reviewed clinical and imaging data from patients who presented with LVOS and underwent endovascular treatment between January 2011 and May 2021. The CBV patterns were analyzed to identify an increase in CBV within the hypoperfused area and estimate infarct patterns within the area of decreased CBV. Comparisons were made between the patients with an increase in CBV and those without, and among the estimated infarct patterns: territorial, cortical wedge, basal ganglia–only, subcortical, and normal CBV. Overall, 243 patients were included. CBV increase in the hypoperfused area was observed in 23.5% of patients. A significantly higher proportion of ICAD was observed in those with increased CBV than in those without (56.4% versus 19.8%; P

Recurrent stroke risk in intracranial atherosclerotic disease remains high despite aggressive medical therapy. While hemodynamic insufficiency appears to be a strong marker of stroke recurrence, natural history studies using various unimodal imaging modalities have shown mixed results, as they likely do not adequately capture the complex local hemodynamic environment generated by a focal stenosis. Computational fluid dynamics, a multimodal tool used to simulate fluid flow and the interactions between fluids and surfaces, has recently been used to illustrate the complex hemodynamic environment surrounding intracranial atherosclerotic lesions and to risk‐stratify patients on the basis of simulated outputs. We aimed to summarize the literature pertaining to computational fluid dynamics use in intracranial atherosclerotic disease and to describe its future potential use in generating more targeted therapies.

Background and Purpose Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired distal perfusion, (2) territorial infarcts due to distal plaque/thrombus embolization, and (3) plaque progression occluding perforators. The objective of the systematic review is to determine whether BZI secondary to ICAS is associated with a higher risk of recurrent stroke or neurological deterioration. Methods As part of this registered systematic review (CRD42021265230), a comprehensive search was performed to identify relevant papers and conference abstracts (with ≥20 patients) reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAS. Subgroup analyses were performed for studies including any BZI versus isolated BZI and those excluding posterior circulation stroke. The study outcome included neurological deterioration or recurrent stroke during follow-up. For all outcome events, corresponding risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated. Results A literature search yielded 4,478 records with 32 selected during the title/abstract triage for full text; 11 met inclusion criteria and 8 studies were included in the analysis (n=1,219 patients; 341 with BZI). The meta-analysis demonstrated that the RR of outcome in the BZI group compared to the no BZI group was 2.10 (95% CI 1.52–2.90). Limiting the analysis to studies including any BZI, the RR was 2.10 (95% CI 1.38–3.18). For isolated BZI, RR was 2.59 (95% CI 1.24–5.41). RR was 2.96 (95% CI 1.71–5.12) for studies only including anterior circulation stroke patients. Conclusion This systematic review and meta-analysis suggests that the presence of BZI secondary to ICAS may be an imaging biomarker that predicts neurological deterioration and/or stroke recurrence.

Background and Purpose Vessel recanalization after cerebral venous thrombosis (CVT) is associated with favorable outcomes and lower mortality. Several studies examined the timing and predictors of recanalization after CVT with mixed results. We aimed to investigate predictors and timing of recanalization after CVT. Methods We used data from the multicenter, international AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from January 2015 to December 2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Prespecified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize. Results Among the 551 patients (mean age, 44.4±16.2 years, 66.2% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. The median time to first follow-up imaging study was 110 days (interquartile range, 60–187). In multivariable analysis, older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03–1.07), male sex (OR, 0.44; 95% CI, 0.24–0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29–0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after CVT diagnosis. Conclusion Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority recanalization occurred early in the disease course suggesting limited further recanalization with anticoagulation beyond 3 months. Large prospective studies are needed to confirm our findings.

Introduction Background: Patients with acute strokes with large infarct size are traditionally excluded from endovascular therapies, as like as clinical care. However, questions remain with respect to the safety and efficacy of EVT in these patients. Methods We conducted a meta‐analysis based on pooled data from SELECT 2 trial [1], ANGEL‐ASPECT trial [2], RESCUE Japan [3], and HERMES study [4]. We explored the efficacy of EVT for large infarcts to achieve a favorable 90‐day modified Rankin Scale. Also, we compared favorable outcomes following EVT in those with a core infarct at baseline of more than 70 ml, delayed thrombectomy of more than 6 hours, older than 75 years, and those who received concomitant IV thrombolysis. We also examined the pooled rate of hemorrhagic transformation following EVT in large core strokes. Results This meta‐analysis showed a statistically significant higher rate of favorable outcome in subjects with extremely large infarct size who undergone EVT compared to those who were managed by medical therapy alone (RR: 1.41, 95% CI: [1.05‐1.98], p: 0.03). In the subgroups of patients with core size > 70ml (RR: 1.51, 95% CI: [1.23‐1.87]), late window presentation (LKN to randomization ≥ 6 hours), (RR: 1.53, 95% CI: [1.27‐1.84]), or those 75 or older than 75 years old (RR: 1.43, 95% CI: [1.12‐1.84]), EVT was associated with higher rates of favorable 90‐day mRS score of 0‐3 compared to medical therapy alone. However, EVT was not associated with better outcomes in those who received IV thrombolysis (RR: 1.37, 95% CI: [0.93‐2.01]. Based on pooled data from SELECT‐2, ANGEL‐ASPECT, and RESCUE Japan trials, the overall rate of early symptomatic hemorrhagic transformation among cases with ASPECT 0‐5 in the thrombectomy group was not significantly higher compared to patients who were managed non‐surgically (OR 1.75, 95% CI: [0.89‐3.47]). Conclusion Endovascular therapy is a reasonable option for the management of large infarcts. EVT results in favorable outcome by a delayed thrombectomy for a large core infarct and in older patients.

Background The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee established the “Brief Practice Update” format to provide up‐to‐date recommendations on focused relevant clinical questions. In this Brief Practice Update, we review current evidence and provide recommendations for endovascular treatment (EVT) in patients with acute large‐vessel occlusion of the basilar artery. Methods The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee conducted a systematic review, including the recent randomized clinical trials of EVT for acute ischemic stroke attributable to basilar artery occlusion, and summarized relevant data to provide recommendations for clinical practice. The Guidelines and Practice Standards quality committee reviewed the findings to ensure adherence to the Society of Vascular and Interventional Neurology internal evidence evaluation guidelines before review by the Society of Vascular and Interventional Neurology board members for societal endorsement. Results Evidence favors EVT for basilar artery occlusion in comparison to medical management alone in patients with moderate to severe stroke. We formulated the level of evidence and the class of recommendation in the context of 5 clinical questions. Conclusions In this brief practice statement, we share general recommendations on EVT for acute ischemic stroke attributable to large‐vessel occlusion of the basilar artery. Recent randomized controlled trials, Basilar Artery Occlusion Chinese Endovascular (BAOCHE) trial and Endovascular Treatment for Acute Basilar‐Artery Occlusion (ATTENTION), and a meta‐analysis of all randomized controlled trials support EVT in patients with moderate to severe basilar artery occlusion stroke symptoms.

Background For acute proximal intracranial artery occlusions, contact aspiration may be more effective than stent‐retriever for first‐line reperfusion therapy. Due to the lack of data regarding medium vessel occlusion thrombectomy, we evaluated outcomes according to first‐line technique in a large, multicenter registry. Methods Imaging, procedural, and clinical outcomes of patients with acute proximal medium vessel occlusions (M2, A1, or P1) or distal medium vessel occlusions (M3, A2, P2, or further) treated at 37 sites in 10 countries were analyzed according to first‐line endovascular technique (stent‐retriever versus aspiration). Multivariable logistic regression and propensity‐score matching were used to estimate the odds of the primary outcome, expanded Thrombolysis in Cerebral Infarction score of 2b–3 (“successful recanalization”), as well as secondary outcomes (first‐pass effect, expanded Thrombolysis in Cerebral Infarction 2c‐3, intracerebral hemorrhage, and 90‐day modified Rankin scale, 90‐day mortality) between treatment groups. Results Of the 440 included patients (44.5% stent‐retriever versus 55.5% aspiration), those treated with stent‐retriever had lower baseline Alberta Stroke Program Early Computed Tomography Scale scores (median 8 versus 9; P

Background Identifying factors associated with delayed diagnosis of cerebral venous thrombosis (CVT) can inform future strategies for early detection. Methods and Results We conducted a retrospective cohort study including all participants from ACTION‐CVT (Anticoagulation in the Treatment of Cerebral Venous Thrombosis) study who had dates of neurologic symptom onset and CVT diagnosis available. Delayed diagnosis was defined as CVT diagnosis occurring in the fourth (final) quartile of days from symptom onset. The primary study outcome was modified Rankin Scale score of ≤1 at 90 days; secondary outcomes included partial/complete CVT recanalization on last available imaging and modified Rankin Scale score of ≤2. Logistic regression analyses were used to identify independent variables associated with delayed diagnosis and to assess the association of delayed diagnosis and outcomes. A total of 935 patients were included in our study. Median time from symptom onset to diagnosis was 4 days (interquartile range, 1–10 days). Delayed CVT diagnosis (time to diagnosis >10 days) occurred in 212 patients (23%). Isolated headache (adjusted odds ratio [aOR], 2.36 [95% CI, 1.50–3.73]; P10 days after symptom onset. Delayed CVT diagnosis was associated with the symptom of isolated headache and was not associated with adverse clinical outcomes.

Vascular imaging is an essential tool to appropriately diagnose and treat intracranial saccular aneurysms. There is extensive heterogeneity in aneurysm characteristics including location, size, shape, patient demographics, and clinical status that leads to a great diversity in both surgical and endovascular treatment options. This variability may elicit confusion when deciding the most appropriate imaging paradigm for an individual patient at particular time points. A collection of pre‐ and posttreatment scales and grades exist, but there is no current consensus on which one to implement. In this review, we discuss the key advantages and disadvantages of the available imaging modalities and how each can guide management. We also review novel imaging tools that are likely to alter the diagnostic landscape of intracranial aneurysms in the coming years.

Background Time is considered a fundamental driver of treatment success in ischemic stroke reperfusion therapy. First‐pass reperfusion (FPR) is associated with improved outcomes. We explored the association between time to reperfusion, FPR, and functional outcomes in an analysis of the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) registry data. Methods Registry patients with anterior circulation stroke, treated with endovascular thrombectomy and achieving complete or near‐complete expanded Thrombolysis in Cerebral Infarction scale (eTICI) 2c/3 reperfusion per core laboratory assessment were included. FPR was considered eTICI 2c/3 reperfusion in a single device pass. Patients undergoing multipass reperfusion required ≥2 device passes to achieve the same, total, or near‐total reperfusion (eTICI 2c/3). Logistic regression was used to model functional independence, defined as a modified Rankin scale score of 0 to 2 at 3 months, as a function of time to reperfusion, comparing FPR and multipass reperfusion patient populations. Results Of the 984 patients in the STRATIS registry, 563 patients achieved eTICI 2c/3 reperfusion of anterior circulation large‐vessel occlusions and were eligible for inclusion in the analysis. In patients undergoing multipass reperfusion (n=186), increased time to treatment was associated with a decreased likelihood of a good clinical outcome. Odds ratio for every 60‐minute delay to treatment: 0.71 (95% CI, 0.55–0.90; P=0.005). However, in patients undergoing FPR (n=377), no association between increased time to treatment and good clinical outcomes was observed (odds ratio for every 60‐minute delay to treatment, 0.93 [95% CI, 0.79–1.09]; P=0.347). Conclusion First‐pass reperfusion may compensate for the effects of delays to reperfusion on functional outcomes in ischemic stroke.

Abstract Identifying the cerebral arterial branches is essential for undertaking a computational approach to cerebrovascular imaging. However, the complexity and inter-individual differences involved in this process have not been thoroughly studied. We used machine learning to examine the anatomical profile of the cerebral arterial tree. The method is less sensitive to inter-subject and cohort-wise anatomical variations and exhibits robust performance with an unprecedented in-depth vessel range. We applied machine learning algorithms to disease-free healthy control subjects (n = 42), patients with stroke with intracranial atherosclerosis (ICAS) (n = 46), and patients with stroke mixed with the existing controls (n = 69). We trained and tested 70% and 30% of each study cohort, respectively, incorporating spatial coordinates and geometric vessel feature vectors. Cerebral arterial images were analyzed based on the ‘segmentation-stacking’ method using magnetic resonance angiography. We precisely classified the cerebral arteries across the exhaustive scope of vessel components using advanced geometric characterization, redefinition of vessel unit conception, and post-processing algorithms. We verified that the neural network ensemble, with multiple joint models as the combined predictor, classified all vessel component types independent of inter-subject variations in cerebral arterial anatomy. The validity of the categorization performance of the model was tested, considering the control, ICAS, and control-blended stroke cohorts, using the area under the receiver operating characteristic (ROC) curve and precision-recall curve. The classification accuracy rarely fell outside each image’s 90–99% scope, independent of cohort-dependent cerebrovascular structural variations. The classification ensemble was calibrated with high overall area rates under the ROC curve of 0.99–1.00 [0.97–1.00] in the test set across various study cohorts. Identifying an all-inclusive range of vessel components across controls, ICAS, and stroke patients, the accuracy rates of the prediction were: internal carotid arteries, 91–100%; middle cerebral arteries, 82–98%; anterior cerebral arteries, 88–100%; posterior cerebral arteries, 87–100%; and collections of superior, anterior inferior, and posterior inferior cerebellar arteries, 90–99% in the chunk-level classification. Using a voting algorithm on the queued classified vessel factors and anatomically post-processing the automatically classified results intensified quantitative prediction performance. We employed stochastic clustering and deep neural network ensembles. Ma-chine intelligence-assisted prediction of vessel structure allowed us to personalize quantitative predictions of various types of cerebral arterial structures, contributing to precise and efficient decisions regarding the cerebrovascular disease.

Background and Purpose High-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere. Methods We used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis–Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis. Results Among 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032). Conclusions Our findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.

Background and Purpose Various mechanisms are involved in the etiology of stroke caused by atherosclerosis of the middle cerebral artery (MCA). Here, we compared differences in plaque nature and hemodynamic parameters according to stroke mechanism in patients with MCA atherosclerosis. Methods Consecutive patients with asymptomatic and symptomatic MCA atherosclerosis (≥50% stenosis) were enrolled. MCA plaque characteristics (location and plaque enhancement) and wall shear stress (WSS) were measured using high-resolution vessel wall and four-dimensional flow magnetic resonance imaging, respectively, at five points (initial, upstream, minimal lumen, downstream, and terminal). These parameters were compared between patients with asymptomatic and symptomatic MCA atherosclerosis with infarctions of different mechanisms (artery-to-artery embolism vs. local branch occlusion). Results In total, 110 patients (46 asymptomatic, 32 artery-to-artery embolisms, and 32 local branch occlusions) were investigated. Plaques were evenly distributed in the MCA of patients with asymptomatic MCA atherosclerosis, more commonly observed in the distal MCA of patients with artery-to-artery embolism, and in the middle MCA of patients with local branch occlusion. Maximum WSS and plaque enhancement were more prominent in the minimum lumen area of patients with asymptomatic MCA atherosclerosis or those with local branch occlusion, and were more prominent in the upstream area in those with artery-to-artery embolism. The elevated variability in the maximum WSS was related to stroke caused by artery-to-artery embolism. Conclusion Stroke caused by artery-to-artery embolism was related to plaque enhancement and the highest maximum WSS at the upstream point of the plaque, and was associated with elevated variability of maximum WSS.

Background We identified risk factors, derived and validated a prognostic score for poor neurological outcome and death for use in cerebral venous thrombosis (CVT). Methods We performed an international multicenter retrospective study including consecutive patients with CVT from January 2015 to December 2020. Demographic, clinical, and radiographic characteristics were collected. Univariable and multivariable logistic regressions were conducted to determine risk factors for poor outcome, mRS 3-6. A prognostic score was derived and validated. Results A total of 1,025 patients were analyzed with median 375 days (interquartile range [IQR], 180 to 747) of follow-up. The median age was 44 (IQR, 32 to 58) and 62.7% were female. Multivariable analysis revealed the following factors were associated with poor outcome at 90- day follow-up: active cancer (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.62 to 27.14; P

Background Clinical and radiographic outcomes after mechanical thrombectomy in the setting of COVID‐19 infection remain poorly characterized. We sought to determine how COVID‐19 status affects mechanical thrombectomy outcomes in the real‐world setting in the United States. Methods The prospectively maintained multicenter mechanical thrombectomy registry from the Society of Vascular and Interventional Neurology was queried for baseline clinical characteristics among patients with and without COVID‐19 who underwent mechanical thrombectomy between March 1 and December 31, 2020 at 12 sites. Primary outcome was the likelihood of good neurological outcomes (90 day modified Rankin scale 0–2) among patients with COVID‐19 treated with endovascular thrombectomy, which was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b, 2c, and 3). Secondary outcomes included National Institutes of Health Stroke Scale at 24 hours. Results Among 915 patients who underwent mechanical thrombectomy during the study period, 51 patients were positive for COVID‐19 (5.6%). Univariate analysis revealed that compared with patients who were COVID‐19 negative, patients who were positive for COVID‐19 were more likely to be male, nonsmokers, have lower Alberta Stroke Program Early CT Score, and present with intracranial internal carotid artery occlusions (Table 1). They were also less likely to achieve successful reperfusion. Multivariable analysis, however, failed to identify any independent associations with COVID‐19 positive status. Conclusion In our cohort, patients postive for COVID‐19 with acute ischemic stroke who undergo mechanical thrombectomy have similar baseline characteristics, imaging features, procedural, and clinical outcomes compared to patients who are negative for COVID‐19 in multivariate analysis. Further analyses are warranted.

ObjectiveAtrial fibrillation is one of the major risk factors of ischemic stroke. Endovascular thrombectomy (EVT) has become the standard treatment for acute ischemic stroke with large vessel occlusion. However, data regarding the impact of AF on the outcome of patients with acute ischemic stroke treated with mechanical thrombectomy are controversial. The aim of our study was to determine whether atrial fibrillation modifies the functional outcome of patients with anterior circulation acute ischemic stroke receiving EVT.MethodsWe reviewed 273 eligible patients receiving EVT from January 2019 to January 2022 from 3 comprehensive Chinese stroke centers, of whom 221 patients were recruited. Demographics, clinical, radiological and treatment characteristics, safety outcomes, and functional outcomes were collected. Modified Rankin scale (mRS) score ≤ 2 at 90 days was defined as a good functional outcome.ResultsIn our cohort, 79 patients (35.74%) were eventually found to have AF. Patients with AF were elder (70.08 ± 11.72 vs. 61.82 ± 13.48 years, p = 0.000) and less likely to be males (54.43 vs. 73.94%, p = 0.03). The significant reperfusion rate (modified thrombolysis in cerebral infarction 2b-3) was 73.42 and 83.80% in patients with and without AF, respectively (p = 0.064). The good functional outcome (90-day modified Rankin scale: 0 to 2) rate was 39.24 and 44.37% in patients with and without AF, respectively (p = 0.460) after adjusting multiple confounding factors. There was no difference in the presence of symptomatic intracerebral hemorrhage between the two groups (10.13 vs. 12.68%, p = 0.573).ConclusionDespite their older age, AF patients achieved similar outcomes as non-AF patients with anterior circulation occlusion treated with endovascular therapy.

Background Intracranial atherosclerotic disease (ICAD) is a common cause of posterior circulation acute ischemic stroke. We aimed to compare baseline characteristics, recanalization rates, and clinical outcomes in patients with acute basilar occlusion due to underlying ICAD to patients with other causes of occlusion. Methods The Trevo Registry (ClinicalTrials.gov Identifier: NCT02040259) was a prospective open‐label mechanical thrombectomy registry that included 2008 patients from 76 sites across 12 countries. For a secondary analysis, we selected patients with isolated acute basilar occlusion. We then classified patients into 2 groups: patients with acute basilar artery occlusion due to ICAD (ICAD group) and patients with acute basilar occlusion due to another cause (non‐ICAD group). Results We identified 90 subjects with acute basilar occlusion. According to stroke mechanism, there were 9 (10.0%) patients in the ICAD group and 81 (90.0%) in the non‐ICAD group. There was a significant difference (P=0.001) in the lesion location between the 2 groups, with 60.5% of non‐ICAD occlusions located in the distal region and no ICAD occlusions there. The 2 groups showed a significant difference (P=0.003) for rescue therapy with balloon angioplasty, with 33.3% in the ICAD group and 1.2% in the non‐ICAD group, respectively. In a multivariable model adjusted for age, baseline National Institutes of Health Stroke Scale, and intravenous tissue‐type plasminogen activator (tPA), the odds of 90‐day death (odds ratio=4.6; P=0.10) were higher for atherosclerotic subjects. Conclusion Acute basilar occlusions related to ICAD showed a similar good clinical outcome (modified Rankin scale (mRS) 0–2) and a tendency for a higher rate of 90‐day mortality compared with non‐ICAD occlusions.

Abstract Background Early prehospital stroke identification is crucial for goal directed hospital admission especially in rural areas. However, clinical prehospital stroke scales are designed to identify any stroke but cannot sufficiently differentiate hemorrhagic from ischemic stroke, including large vessel occlusion (LVO) amenable to mechanical thrombectomy. We report on a novel small, portable and battery driven point-of-care ultrasound system (SONAS®) specifically developed for mobile non-invasive brain perfusion ultrasound (BPU) measurement after bolus injection of an echo-enhancing agent suitable for the use in prehospital stroke diagnosis filling a current, unmet and critical need for LVO identification. Methods In a phase I study of healthy volunteers we performed comparative perfusion-weighted magnetic resonance imaging (PWI) and BPU measurements, including safety analysis. Results Twelve volunteers (n = 7 females, n = 5 males, age ranging between 19 and 55 years) tolerated the measurement extremely well including analysis of blood–brain barrier integrity, and the correlation coefficient between the generated time kinetic curves after contrast agent bolus between PWI and BPU transducers ranged between 0.89 and 0.76. Conclusions Mobile BPU using the SONAS® device is feasible and safe with results comparable to PWI. When applied in conjunction with prehospital stroke scales this may lead to a more accurate stroke diagnosis and patients bypassing regular stroke units to comprehensive stroke centers. Further studies are needed in acute stroke patients and in the prehospital phase including assessment of immediate and long-term morbidity and mortality in stroke. Trial registration: Clinical trials.gov, registered 28.Sep.2017, Identifier: NCT03296852.

In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect in preclinical models of stroke and a very good pharmacokinetic and safety profile in healthy volunteers, is a promising first-in-class aptamer with the potential to address this huge unmet need. This protocol establishes the clinical trial procedures to conduct a Phase Ib/IIa clinical study (APRIL) to assess ApTOLL tolerability, safety, pharmacokinetics, and biological effect in patients with AIS who are eligible for EVT. This will be a multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to evaluate the administration of ApTOLL together with EVT in patients with AIS. The study population will be composed of men and non-pregnant women with confirmed AIS with a

Background Systems of care surrounding endovascular therapy for stroke have garnered much attention in recent years. In‐hospital metrics, such as “door‐to‐puncture” and procedure times have been areas for quality improvement. The temporal trend and clinical significance of prehospital “onset‐to‐door” time, however, remains unknown. Methods We performed a systematic review of time metric data from all published randomized controlled and investigational device exemption trials involving endovascular therapy for stroke between 2005 and 2019 (n=26). Second, we conducted a record‐level observational analysis on a total of 3512 patients from 3 real‐world registries (Mechanical Embolus Removal in Cerebral Ischemia [MERCI], Thrombectomy REvascularization of Large Vessel Occlusions in Acute Ischemic Stroke [TREVO], and TREVO Stent‐Retriever Acute Stroke [TRACK]), together with 4 prospective trials (MERCI trial, Multi‐MERCI, TREVO‐EU, and TREVO‐2). Only patients receiving mechanical thrombectomy within 9 hours from onset‐to‐puncture time were included. Predictors of good outcome were identified using generalized linear mixed modeling. Results Door‐to‐puncture times (slope=−5.83 min/y; R2=0.25; P=0.046), procedure times (slope=−3.78 min/y; R2=0.54; P

Background: For prognosis of stroke, measurement of the diffusion-perfusion mismatch is a common practice for estimating tissue at risk of infarction in the absence of timely reperfusion. However, perfusion-weighted imaging (PWI) adds time and expense to the acute stroke imaging workup. We explored whether a deep convolutional neural network (DCNN) model trained with diffusion-weighted imaging obtained at admission could predict final infarct volume and location in acute stroke patients. Methods: In 445 patients, we trained and validated an attention-gated (AG) DCNN to predict final infarcts as delineated on follow-up studies obtained 3 to 7 days after stroke. The input channels consisted of MR diffusion-weighted imaging (DWI), apparent diffusion coefficients (ADC) maps, and thresholded ADC maps with values less than 620 × 10−6 mm2/s, while the output was a voxel-by-voxel probability map of tissue infarction. We evaluated performance of the model using the area under the receiver-operator characteristic curve (AUC), the Dice similarity coefficient (DSC), absolute lesion volume error, and the concordance correlation coefficient (ρc) of the predicted and true infarct volumes. Results: The model obtained a median AUC of 0.91 (IQR: 0.84–0.96). After thresholding at an infarction probability of 0.5, the median sensitivity and specificity were 0.60 (IQR: 0.16–0.84) and 0.97 (IQR: 0.93–0.99), respectively, while the median DSC and absolute volume error were 0.50 (IQR: 0.17–0.66) and 27 ml (IQR: 7–60 ml), respectively. The model’s predicted lesion volumes showed high correlation with ground truth volumes (ρc = 0.73, p

Intracranial atherosclerotic disease is the most common cause of stroke worldwide. The past decade of research in intracranial atherosclerotic disease has led to marginally improved medical therapy, yet recurrent stroke rates remain high. Despite the enormous global burden of disease, we lack effective clinical acumen to appropriately risk stratify patients and optimize the therapeutic approach. In this review, we examine our current understanding of intracranial atherosclerotic disease pathophysiology, imaging techniques, lifestyle, medical therapy, and endovascular strategies. We also present steps needed to incorporate imaging and serum biomarkers in intracranial atherosclerotic disease to facilitate individualized treatment plans and realize the potential of precision medicine in this global health disorder. Trials in the next decade should be targeted to help us gain a better understanding of key mechanisms and disease course with an ultimate goal of improving long‐term patient outcomes.

Background The COVID‐19 pandemic has disproportionately affected Black and Hispanic communities, whose stroke care has been previously shown to experience existing disparities. We sought to evaluate how these disparities in stroke care and in‐hospital mortality have been affected by the COVID‐19 pandemic. Methods In this retrospective observational cohort study, we evaluated stroke hospitalizations in the Society of Vascular and Interventional Neurology COVID‐19 registry. We compared stroke characteristics between non‐Hispanic White, non‐Hispanic Black, and Hispanic patients pre–COVID‐19 and post–COVID‐19 (March–July 2019 versus March–July 2020) and evaluated whether racial and ethnic differences present before the pandemic were exacerbated during the pandemic. Our primary outcome was in‐hospital mortality/discharge to hospice, and secondary outcomes were acute treatment use. Results Of the 4908 included patients, numerically fewer non‐Hispanic White and Hispanic patients were evaluated during COVID‐19. Non‐Hispanic White and non‐Hispanic Black patients with large‐vessel occlusion were more likely to undergo thrombectomy (P

Background To compare stroke severity, as well as usage and outcomes of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) in patients with and without dementia. Methods Study of the US hospitalizations with AIS and documented National Institutes of Health Stroke Scale scores from October 1, 2016, to December 31, 2017. AIS hospitalizations with documented dementia were compared with AIS hospitalizations without dementia for stroke severity at onset, use of MT, and outcomes at discharge. Outcomes included favorable discharge disposition (home without assistance), in‐hospital mortality, and radiographic intracranial hemorrhage. Results Among 179 665 AIS admissions with recorded National Institutes of Health Stroke Scale score during the 15‐month study period, 18 255 (10.2%) had preexisting dementia (62.5% women). The median age at stroke was 84 (interquartile range, 78–89) versus 69 (interquartile range, 59–79) years; and median presenting National Institutes of Health Stroke Scale score was 7 (interquartile range, 3–15) versus 4 (interquartile range, 2–10) in hospitalizations with versus without dementia. There was a stepwise association between increasing severity of the index stroke and the prevalence of dementia. In multivariable analysis, dementia was associated with significantly lower (odds ratio [OR], 0.43 [95% CI, 0.35–0.53]; P

Large clinical trials have helped establish the benefit of endovascular treatment (EVT) in patients with acute ischemic stroke with large vessel occlusion and small infarct core volume as determined by scores ≥6 on the Alberta Stroke Program Early CT Scores. Several small studies have suggested that patients with large infarct core volume (LICV) may also benefit from EVT. Currently, at least 6 randomized clinical trials are examining the benefit of extending EVT to this population of patients with acute ischemic stroke. These trials were independently conceived and have significant differences in their inclusion criteria. Understanding these inclusion criteria and other differences in trial design is pivotal for the field to interpret the upcoming results of these trials. In this review, the designs of the 6 trials are summarized and compared. Specific differences are described, including (1) the rationale for EVT treatment in patients with LICV, (2) how to define LICV and the imaging modality used to identify LICV, (3) inclusion of an Alberta Stroke Program Early CT Score 0 to 5 versus 3 to 5, (4) use of the mismatch between blood flow and the size of infarct as an inclusion criterion, and (5) inclusion of early window and/or late window patients. The potential impact of these trial results on current guidelines for acute ischemic stroke is discussed. Differences in trial design as well as inclusion and exclusion criteria may influence trial outcomes. The implications of these trial results will likely be enhanced by a pooled analysis.

The objective of this study is to quantify the increase in brain-under-protection time that may be achieved with pre-hospital compared with the post-arrival start of neuroprotective therapy among patients undergoing endovascular thrombectomy. In order to do this, a comparative analysis was performed of two randomized trials of neuroprotective agents: (1) pre-hospital strategy: Field administration of stroke therapy-magnesium (FAST–MAG) Trial; (2) in-hospital strategy: Efficacy and safety of nerinetide for the treatment of acute ischemic stroke (ESCAPE-NA1) Trial. In the FAST-MAG trial, among 1,041 acute ischemic stroke patients, 44 were treated with endovascular reperfusion therapy (ERT), including 32 treated with both intravenous thrombolysis and ERT and 12 treated with ERT alone. In the ESCAPE-NA1 trial, among 1,105 acute ischemic stroke patients, 659 were treated with both intravenous thrombolysis and ERT, and 446 were treated with ERT alone. The start of the neuroprotective agent was sooner after onset with pre-hospital vs. in-hospital start: 45 m (IQR 38–56) vs. 122 m. The neuroprotective agent in FAST–MAG was started 8 min prior to ED arrival compared with 64 min after arrival in ESCAPE–NA1. Projecting modern endovascular workflows to FAST–MAG, the total time of “brain under protection” (neuroprotective agent start to reperfusion) was greater with pre-hospital than in-hospital start: 94 m (IQR 90–98) vs. 22 m. Initiating a neuroprotective agent in the pre-hospital setting enables a faster treatment start, yielding 72 min additional brain protection time for patients with acute ischemic stroke. These findings provide support for the increased performance of ambulance-based, pre-hospital treatment trials in the development of neuroprotective stroke therapies.