Endovascular Treatment of Medium Vessel Occlusion Stroke.

Approximately one-third of acute ischemic strokes with an identifiable vessel occlusion are caused by medium vessel occlusion (MeVO), that is, nonlarge vessel occlusions that are potentially amenable to endovascular treatment (EVT). Management of patients with MeVO is challenging in many ways: detecting MeVOs can be challenging, particularly for inexperienced physicians, and in busy clinical routine, MeVOs, therefore, remain sometimes undiagnosed. While the clinical course of MeVO stroke with medical management, including intravenous thrombolysis, is by no means, benign, it is more favorable compared with large vessel occlusion. At the same time, EVT complication rates are higher, and thus, the marginal benefit of EVT beyond best medical management is expected to be smaller and more challenging to detect if it were present. Several randomized controlled trials are currently underway to investigate whether and to what degree patients with MeVO may benefit from EVT and will soon provide robust data for evidence-based MeVO EVT decision-making. In this review, we discuss different ways of defining MeVOs, strategies to optimize MeVO detection on imaging, and considerations for EVT decision-making in the setting of MeVO stroke. We discuss the technical challenges related to MeVO EVT and conclude with an overview of currently ongoing MeVO EVT trials.

Influence of Infarct Morphology and Patterns on Cognitive Outcomes After Endovascular Thrombectomy.

BACKGROUND: To assess the association of qualitative and quantitative infarct characteristics and 3 cognitive outcome tests, namely the Montreal Cognitive Assessment (MOCA) for mild cognitive impairment, the Boston Naming Test for visual confrontation naming, and the Sunnybrook Neglect Assessment Procedure for neglect, in large vessel occlusion stroke. METHODS: Secondary observational cohort study using data from the randomized-controlled ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke), in which patients with large vessel occlusion undergoing endovascular treatment were randomized to receive either intravenous Nerinetide or placebo. MOCA, Sunnybrook Neglect Assessment Procedure, and 15-item Boston Naming Test were obtained at 90 days. Total infarct volume, gray matter, and white matter infarct volumes were manually measured on 24-hour follow-up imaging. Infarcts were also visually classified as either involving the gray matter only or both the gray and white matter and scattered versus territorial. Associations of infarct variables and cognitive outcomes were analyzed using multivariable ordinal or binary logistic regression models. RESULTS: Of 1105 patients enrolled in ESCAPE-NA1, 1026 patients with visible infarcts on 24-hour follow-up imaging were included. MOCA and Sunnybrook Neglect Assessment Procedure were available for 706 (68.8%) patients and the 15-item Boston Naming Test was available for 682 (66.5%) patients. Total infarct volume was associated with worse MOCA scores (adjusted common odds ratio per 10 mL increase, 1.05 [95% CI, 1.04-1.06]). After adjusting for baseline variables and total infarct volume, mixed gray and white matter involvement (versus gray matter-only adjusted common odds ratio, 1.92 [95% CI, 1.37-2.69]), white matter infarct volume (adjusted common odds ratio per 10 mL increase 1.36 [95% CI, 1.18-1.58]) and territorial (versus scattered) infarct pattern (adjusted common odds ratio, 1.65 [95% CI, 1.15-2.38]) were associated with worse MOCA scores. Results for Sunnybrook Neglect Assessment Procedure and 15-item Boston Naming Test were similar, except for the territorial infarct pattern, which did not reach statistical significance in multivariable analysis. CONCLUSIONS: Besides total infarct volume, infarcts that involve the white matter and that show a territorial distribution were associated with worse cognitive outcomes, even after adjusting for total infarct volume.

What Is a Meaningful Difference When Using Infarct Volume as the Primary Outcome?: Results From the HERMES Database.

BACKGROUND: Ischemic stroke lesion volume at follow-up is an important surrogate outcome for acute stroke trials. We aimed to assess which differences in 48-hour lesion volume translate into meaningful clinical differences. METHODS: We used pooled data from 7 trials investigating the efficacy of endovascular treatment for anterior circulation large vessel occlusion in acute ischemic stroke. We assessed 48-hour lesion volume follow-up computed tomography or magnetic resonance imaging. The primary outcome was a good functional outcome, defined as modified Rankin Scale (mRS) scores of 0 to 2. We performed multivariable logistic regression to predict the probability of achieving mRS scores of 0 to 2 and determined the differences in 48-hour lesion volume that correspond to a change of 1%, 5%, and 10% in the adjusted probability of achieving mRS scores of 0 to 2. RESULTS: In total, 1665/1766 (94.2%) patients (median age, 68 [interquartile range, 57-76] years, 781 [46.9%] female) had information on follow-up ischemic lesion volume. Computed tomography was used for follow-up imaging in 83% of patients. The median 48-hour lesion volume was 41 (interquartile range, 14-120) mL. We observed a linear relationship between 48-hour lesion volume and mRS scores of 0 to 2 for adjusted probabilities between 65% and 20%/volumes <80 mL, although the curve sloped off for lower mRS scores of 0-2 probabilities/higher volumes. The median differences in 48-hour lesion volume associated with a 1%, 5%, and 10% increase in the probability of mRS scores of 0 to 2 for volumes <80 mL were 2 (interquartile range, 2-3), 10 (9-11), and 20 (18-23) mL, respectively. We found comparable associations when assessing computed tomography and magnetic resonance imaging separately. CONCLUSIONS: A difference of 2, 10, and 20 mL in 48-hour lesion volume, respectively, is associated with a 1%, 5%, and 10% absolute increase in the probability of achieving good functional outcome. These results can inform the design of future stroke trials that use 48-hour lesion volume as the primary outcome.

Endovascular Treatment for Cerebral Venous Thrombosis: Applying Lessons Learned from Clinical Trials of Endovascular Treatment in Acute Arterial Ischemic Stroke.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare but severely disabling form of stroke. Acute treatment mainly consists of medical management, since there is no robust evidence suggesting the benefit of endovascular treatment for CVT. Given the relative lack of data to guide acute treatment decision-making, CVT treatment decisions are mostly made on a case-by-case basis. In some ways, the current status quo of endovascular treatment for CVT resembles the state of endovascular treatment for acute ischemic stroke before the wave of major positive large vessel occlusion endovascular treatment trials in 2015. SUMMARY: The current state of evidence with regard to endovascular CVT treatment is summarized, parallels to acute ischemic stroke are drawn, and it is discussed how the lessons learned from the evolution of acute ischemic stroke endovascular treatment (EVT) trials could be applied to designing a trial of endovascular treatment for CVT. The review ends by outlining possible scenarios for the future of endovascular CVT treatment. KEY MESSAGES: CVT is a serious disease, affecting young patients and their families, and harbors a considerable social and economic burden. Working toward high-level evidence for the best possible treatment strategy and exploring a possible role for EVT to improve outcomes in CVT needs to remain a high priority in stroke research.

Modeling diffusion-weighted imaging lesion expansion between 2 and 24 h after endovascular thrombectomy in acute ischemic stroke.

PURPOSE: Diffusion-weighted imaging (DWI) lesion expansion after endovascular thrombectomy (EVT) is not well characterized. We used serial diffusion-weighted magnetic resonance imaging (MRI) to measure lesion expansion between 2 and 24 h after EVT. METHODS: In this single-center observational analysis of patients with acute ischemic stroke due to large vessel occlusion, DWI was performed post-EVT (< 2 h after closure) and 24-h later. DWI lesion expansion was evaluated using multivariate generalized linear mixed modeling with various clinical moderators. RESULTS: We included 151 patients, of which 133 (88%) had DWI lesion expansion, defined as a positive change in lesion volume between 2 and 24 h. In an unadjusted analysis, median baseline DWI lesion volume immediately post-EVT was 15.0 mL (IQR: 6.6-36.8) and median DWI lesion volume 24 h post-EVT was 20.8 mL (IQR: 9.4-66.6), representing a median change of 6.1 mL (IQR: 1.5-17.7), or a 39% increase. There were no significant associations among univariable models of lesion expansion. Adjusted models of DWI lesion expansion demonstrated that relative lesion expansion (defined as final/initial DWI lesion volume) was consistent across eTICI scores (0-2a, 0.52%; 2b, 0.49%; 2c-3, 0.42%, p = 0.69). For every 1 mL increase in lesion volume, there was 2% odds of an increase in 90-day mRS (OR: 1.021, 95%CI [1.009, 1.034], p < 0.001). CONCLUSION: We observed substantial lesion expansion post-EVT whereby relative lesion expansion was consistent across eTICI categories, and greater absolute lesion expansion was associated with worse clinical outcome. Our findings suggest that alternate endpoints for cerebroprotectant trials may be feasible.

Cost-Effectiveness of Late Endovascular Thrombectomy vs. Best Medical Management in a Clinical Trial Setting and Real-World Setting.

BACKGROUND AND PURPOSE: To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a "real-world" setting. METHODS: Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a "real-world" setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY. RESULTS: Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%-99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%-61.6%), but not the "real-world" setting (acceptability:32.9%-42.6%). CONCLUSION: EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and "real-world" setting, although this was largely related to baseline patient differences favoring the "real-world" EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.

Optimizing Patient-Centered Stroke Care and Research in the Prehospital Setting.

Over the past decades, continuous technological advances and the availability of novel therapies have enabled treatment of more acute medical conditions than ever before. Many of these treatments, such as intravenous thrombolysis and mechanical thrombectomy for acute ischemic stroke, are highly time sensitive. This has raised interest in shifting advanced acute care from hospitals to the prehospital setting. Key objectives of advanced prehospital stroke care may include (1) early targeted treatments in the prehospital setting, for example, intravenous thrombolysis for acute stroke, and (2) advanced prehospital diagnostics such as prehospital large vessel occlusion and intracranial hemorrhage detection, to help inform patient triage and potentially reduce subsequent workload in emergency departments. Major challenges that may hamper a swift transition to more advanced prehospital care are related to conducting clinical trials in the prehospital setting to provide sufficient evidence for emergency interventions, as well as ambulance design, infrastructure, emergency medical service personnel training and workload, and cost barriers. Utilizing new technologies such as telemedicine, mobile stroke units and portable diagnostic devices, customized software applications, and smart storage space management may help surmount these challenges and establish efficient, targeted care strategies that are achievable in the prehospital setting. In this article, we delineate the paradigm of shifting advanced stroke care to the prehospital setting and outline future directions in providing evidence-based, patient-centered prehospital care. While we use acute stroke as an illustrative example, these principles are not limited to stroke patients and can be applied to prehospital triage for any time-critical disease.

Cost-Effectiveness of Endovascular Treatment in Large Vessel Occlusion Stroke With Mild Prestroke Disability: Results From the HERMES Collaboration.

BACKGROUND: The clinical and economic benefit of endovascular treatment (EVT) in addition to best medical management in patients with stroke with mild preexisting symptoms/disability is not well studied. We aimed to investigate cost-effectiveness of EVT in patients with large vessel occlusion and mild prestroke symptoms/disability, defined as a modified Rankin Scale score of 1 or 2. METHODS: Data are from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials), which pooled patient-level data from 7 large, randomized EVT trials. We used a decision model consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes from a health care and a societal perspective. Incremental cost-effectiveness ratio and net monetary benefits were calculated, and a probabilistic sensitivity analysis was performed. RESULTS: EVT in addition to best medical management resulted in lifetime cost savings of $2821 (health care perspective) or $5378 (societal perspective) and an increment of 1.27 quality-adjusted life years compared with best medical management alone, indicating dominance of additional EVT as a treatment strategy. The net monetary benefits were higher for EVT in addition to best medical management compared with best medical management alone both at the higher (100 000$/quality-adjusted life years) and lower (50 000$/quality-adjusted life years) willingness to pay thresholds. Probabilistic sensitivity analysis showed decreased costs and an increase in quality-adjusted life years for additional EVT compared with best medical management only. CONCLUSIONS: From a health-economic standpoint, EVT in addition to best medical management should be the preferred strategy in patients with acute ischemic stroke with large vessel occlusion and mild prestroke symptoms/disability.

Distal Embolization in Relation to Radiological Thrombus Characteristics, Treatment Details, and Functional Outcome.

BACKGROUND: Distal embolization (DE) is a common complication of endovascular treatment (EVT). We investigated the association of radiological thrombus characteristics and treatment details with DE. METHODS: Patients with thin-slice (≤2.5 mm) baseline noncontrast computed tomography and computed tomography angiography from the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) were included. Thrombus annotation was performed manually on coregistered scans by experienced readers. We assessed thrombus location, distance from internal carotid artery terminus, length, perviousness, absolute attenuation, and hyperdense artery sign. In addition, we evaluated balloon guide catheter use during EVT, first-line EVT approach, the number of thrombectomy passes, and prior intravenous thrombolysis administration. DE was defined as the occurrence of emboli distal to the target artery or in new territories during EVT. The association between thrombus characteristics, treatment details, and DE was evaluated using descriptive statistics and multivariable mixed-effects logistic regression, resulting in adjusted odds ratios (aOR) with 95% CI. Interaction between IVT and radiological thrombus characteristics was assessed by adding interaction terms in separate models. RESULTS: In total, 496 out of 1105 (44.9%) ESCAPE-NA1 patients were included. DE was detected in 251 out of 496 patients (50.6%). Patients with DE had longer thrombi (median, 28.5 [interquartile range, 20.8-42.3] mm versus 24.4 [interquartile range, 17.1-32.4] mm; P<0.01). There were no statistically significant differences in the other thrombus characteristics. Factors associated with DE were thrombus length (aOR, 1.02 [95% CI, 1.01-1.04]), balloon guide catheter use (aOR, 0.49 [95% CI, 0.29-0.85]), and number of passes (aOR, 1.24 [95% CI, 1.04-1.47]). In patients with hyperdense artery sign, IVT was associated with reduced odds of DE (aOR, 0.55 [95% CI, 0.31-0.97]), P for interaction=0.04. CONCLUSIONS: DE was associated with longer thrombi, no balloon guide catheter use, and more EVT passes. IVT was associated with a reduced risk of DE in patients with hyperdense artery sign. These findings may support treatment decisions on IVT and EVT approaches.

Infarcts in a New Territory: Insights From the ESCAPE-NA1 Trial.

BACKGROUND: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT, outcomes after INT, and the impact of concurrent treatments with intravenous thrombolysis and nerinetide. METHODS: Data are from ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke), a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in subjects with acute ischemic stroke who underwent endovascular thrombectomy within 12 hours from onset. Concurrent treatment and outcomes were collected as part of the trial protocol. INTs were identified on core lab imaging review of follow-up brain imaging and defined by the presence of infarct in a new vascular territory, outside the baseline target occlusion(s) on follow-up brain imaging (computed tomography or magnetic resonance imaging). INTs were classified by maximum diameter (<2, 2-20, and >20 mm), number, and location. The association between INT and clinical outcomes (modified Rankin Scale and death) was assessed using standard descriptive techniques and adjusted estimates of effect were derived from Poisson regression models. RESULTS: Among 1092 patients, 103 had INT (9.3%, median age 69.5 years, 49.5% females). There were no differences in baseline characteristics between those with versus without INT. Most INTs (91/103, 88.3%) were not associated with visible occlusions on angiography and 39 out of 103 (37.8%) were >20 mm in maximal diameter. The most common INT territory was the anterior cerebral artery (27.8%). Almost half of the INTs were multiple (46 subjects, 43.5%, range, 2-12). INT was associated with poorer outcomes as compared to no INT on the primary outcome of modified Rankin Scale score of 0 to 2 at 90 days (adjusted risk ratio, 0.71 [95% CI, 0.57-0.89]). Infarct volume in those with INT was greater by a median of 21 cc compared with those without, and there was a greater risk of death as compared to patients with no INT (adjusted risk ratio, 2.15 [95% CI, 1.48-3.13]). CONCLUSIONS: Infarcts in a new territory are common in individuals undergoing endovascular thrombectomy for acute ischemic stroke and are associated with poorer outcomes. Optimal therapeutic approaches, including technical strategies, to reduce INT represent a new target for incremental quality improvement of endovascular thrombectomy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02930018.

Cost-effectiveness of Endovascular Treatment for Acute Stroke with Large Infarct: A United States Perspective.

Background The health economic benefit of endovascular treatment (EVT) in addition to best medical management for acute ischemic stroke with large ischemic core is uncertain. Purpose To assess the cost-effectiveness of EVT plus best medical management versus best medical management alone in treating acute ischemic stroke with large vessel occlusion and a baseline Alberta Stroke Program Early CT Score (ASPECTS) 3-5. Materials and Methods This is a secondary analysis of the randomized RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Large Ischemic Core Trial), with enrollment November 2018 to September 2021, in which the primary outcome was the modified Rankin Scale (mRS) score at 90 days. Participants with a baseline ASPECTS 3-5 (on the basis of noncontrast CT and diffusion-weighted imaging) were randomized 1:1 to receive EVT plus best medical management (n = 100) or best medical management alone (n = 102). The primary outcome of the current study was cost-effectiveness, determined according to the incremental cost-effectiveness ratio (ICER). A decision model consisting of a short-term component (cycle length of 3 months) and a long-term Markov state transition component (cycle length of 1 year) was used to estimate expected lifetime costs and quality-adjusted life-years (QALYs) from health care and societal perspectives in the United States. Upper and lower willingness-to-pay (WTP) thresholds were set at $100 000 and $50 000 per QALY, respectively. A deterministic one-way sensitivity analysis to determine the impact of participant age and a probabilistic sensitivity analysis to assess the impact of parameter uncertainty were conducted. Results A total of 202 participants were included in the study (mean age, 76 years ± 10 [SD]; 112 male). EVT plus best medical management resulted in ICERs of $15 743 (health care perspective) and $19 492 (societal perspective). At the lower and upper WTP thresholds, EVT was cost-effective up to 85 and 90 years (health care perspective) and 84 and 89 years (societal perspective) of age, respectively. When analyzing participants with the largest infarcts (ASPECTS 3) separately, EVT was not cost-effective (ICER, $337 072 [health care perspective] and $383 628 [societal perspective]). Conclusion EVT was cost-effective for participants with an ASPECTS 4-5, but not for those with an ASPECTS 3. ClinicalTrials.gov registration no. NCT03702413 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Widjaja in this issue.

No Sex Differences in Mechanical Thrombectomy Time Metrics and Outcomes in Saskatchewan.

BACKGROUND AND PURPOSE: Numerous studies have shown longer pre-hospital and in-hospital workflow times and poorer outcomes in women after acute ischemic stroke (AIS) in general and after endovascular treatment (EVT) in particular. We investigated sex differences in acute stroke care of EVT patients over 5 years in a comprehensive Canadian provincial registry. METHODS: Clinical data of all AIS patients who underwent EVT between January 2017 and December 2022 in the province of Saskatchewan were captured in the Canadian OPTIMISE registry and supplemented with patient data from administrative data sources. Patient baseline characteristics, transport time metrics, and technical EVT outcomes between female and male EVT patients were compared. RESULTS: Three-hundred-three patients underwent EVT between 2017 and 2022: 144 (47.5%) women and 159 (52.5%) men. Women were significantly older (median age 77.5 [interquartile range: 66-85] vs.71 [59-78], p < 0.001), while men had more intracranial internal carotid artery occlusions (48/159 [30.2%] vs. 26/142 [18.3%], p = 0.03). Last-known-well to comprehensive stroke center (CSC)-arrival time (median 232 min [interquartile range 90-432] in women vs. 230 min [90-352] in men), CSC-arrival-to-reperfusion time (median 108 min [88-149] in women vs. 102 min [77-141] in men), reperfusion status (successful reperfusion 106/142 [74.7%] in women vs. 117/158 [74.1%] in men) as well as modified Rankin score at 90 days did not differ significantly. This held true after adjusting for baseline variables in multivariable analyses. CONCLUSION: While women undergoing EVT in the province of Saskatchewan were on average older than men, they were treated just as fast and achieved similar technical and clinical outcomes compared to men.

Toward a Better Understanding of Sex- and Gender-Related Differences in Endovascular Stroke Treatment: A Scientific Statement From the American Heart Association/American Stroke Association.

There are many unknowns when it comes to the role of sex in the pathophysiology and management of acute ischemic stroke. This is particularly true for endovascular treatment (EVT). It has only recently been established as standard of care; therefore, data are even more scarce and conflicting compared with other areas of acute stroke. Assessing the role of sex and gender as isolated variables is challenging because they are closely intertwined with each other, as well as with patients' cultural, ethnic, and social backgrounds. Nevertheless, a better understanding of sex- and gender-related differences in EVT is important to develop strategies that can ultimately improve individualized outcome for both men and women. Disregarding patient sex and gender and pursuing a one-size-fits-all strategy may lead to suboptimal or even harmful treatment practices. This scientific statement is meant to outline knowledge gaps and unmet needs for future research on the role of sex and gender in EVT for acute ischemic stroke. It also provides a pragmatic road map for researchers who aim to investigate sex- and gender-related differences in EVT and for clinicians who wish to improve clinical care of their patients undergoing EVT by accounting for sex- and gender-specific factors. Although most EVT studies, including those that form the basis of this scientific statement, report patient sex rather than gender, open questions on gender-specific EVT differences are also discussed.

Functional Outcomes of Patients ≥85 Years With Acute Ischemic Stroke Following EVT: A HERMES Substudy.

BACKGROUND: Observational studies have shown endovascular treatment (EVT) for acute ischemic stroke to be effective in the elderly, despite resulting in poorer outcomes and higher rates of mortality compared with younger patients. Randomized data on the effect of advanced age on outcomes following EVT are, however, lacking. Our aim was to assess the EVT effect for ischemic stroke in patients aged ≥85 years and the influence of age on outcome in a large, randomized trial dataset. METHODS: Data were from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration, a meta-analysis of 7 randomized trials published between January 1, 2010, and May 31, 2017, that tested the efficacy of EVT. A possible multiplicative interaction effect of age on the relationship between treatment and outcome was investigated. Ordinal logistic regression tested the association between EVT and 90-day functional outcome (modified Rankin Scale, primary outcome) in patients ≥85 years. Multivariable binary logistic regression was performed to compare primary and secondary outcomes (modified Rankin Scale score of 0-2/5-6) of patients ≥85 years versus those <85 years. RESULTS: We included 1764 patients in the analysis, of whom 77 (4.4%) were ≥85 years old. A significant interaction of age and treatment on poor outcome (modified Rankin Scale score of 5-6, P=0.020) and mortality (P=0.031) was observed, with older adults having worse functional outcomes at 90 days compared with younger patients (adjusted common odds ratio, 0.20 [95% CI, 0.13-0.33]). However, a benefit of EVT was observed in the ≥85-year-old patient subgroup (common odds ratio, 4.20 [95% CI, 1.56-11.32]). Age ≥85 years was not significantly associated with differing rates of symptomatic intracerebral hemorrhage or reperfusion (adjusted odds ratio, 1.92 [95% CI, 0.71-5.15] and adjusted odds ratio, 0.91 [95% CI, 0.40-2.06], respectively). CONCLUSIONS: Patients ≥85 years old with independent premorbid function more often achieve good functional outcomes and have lower rates of mortality when treated with EVT compared with conservative management, with an observed treatment effect modification of age on outcome. EVT should therefore not be withheld in this subgroup.

Association of Intravenous Alteplase, Early Reperfusion, and Clinical Outcome in Patients With Large Vessel Occlusion Stroke: Post Hoc Analysis of the Randomized DIRECT-MT Trial.

BACKGROUND: The added value of intravenous alteplase in reperfusing ischemic brain tissue in patients undergoing endovascular treatment and directly presented to an endovascular treatment-capable hospital is uncertain. We conducted this post hoc analysis of a randomized trial (DIRECT-MT [Direct Intraarterial Thrombectomy in Order to Revascularize Acute Ischemic Stroke Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: A Multicenter Randomized Clinical Trial]) to explore the association of intravenous alteplase, early (preendovascular treatment) reperfusion, and clinical outcome and to determine factors which may modify alteplase treatment effect on early reperfusion. METHODS: In this post hoc analysis of the DIRECT-MT randomized trial comparing intravenous alteplase before endovascular treatment versus endovascular treatment only, 623 of 656 randomized patients, with adequate angiographic evaluation for early reperfusion assessment, were included. The association of intravenous alteplase and early reperfusion (defined as expanded Thrombolysis in Cerebral Infarction score ≥2a on angiogram) was assessed using unadjusted comparisons and multivariable logistic regression. RESULTS: Among 623 patients included (317 received intravenous alteplase and 306 did not), early reperfusion occurred in 91 (15%) patients and was associated with better functional outcome (modified Rankin Scale score, 0-2 of 49/91 [54%] versus 178/531 [34%]; adjusted odds ratio, 1.92 [95% CI, 1.15-3.21]; P<0.001). Intravenous alteplase was independently associated with early reperfusion (59/317 [19%] versus 32/306 [10%]; adjusted odds ratio, 2.06 [95% CI, 1.27-3.33]; P=0.003), and the alteplase effect was modified by time from randomization to groin puncture (dichotomized by median, ≤33 minutes; adjusted odds ratio, 1.06 [95% CI, 0.53-2.10] versus >33 minutes; adjusted odds ratio, 4.07 [95% CI, 1.86-8.86]; Pinteraction=0.012). CONCLUSIONS: For patients with large vessel occlusion directly presenting to an endovascular treatment-capable hospital, intravenous alteplase increases early reperfusion when endovascular treatment gets delayed more than approximately half an hour. Thus, intravenous alteplase should be considered if endovascular treatment delays are anticipated by the treating medical team. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03469206.

Thrombectomy With and Without Computed Tomography Perfusion Imaging in the Early Time Window: A Pooled Analysis of Patient-Level Data.

BACKGROUND: The optimal imaging paradigm for endovascular thrombectomy (EVT) patient selection in early time window (0-6 hours) treated acute ischemic stroke patients remains uncertain. We aimed to compare post-EVT outcomes between patients who underwent prerandomization basic (noncontrast computed tomography [CT], CT angiography only) versus additional advanced imaging (computed tomography perfusion [CTP] imaging) and to determine the association of performance of prerandomization CTP imaging with clinical outcomes. METHODS: The HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) pooled patient-level data from randomized controlled trials comparing EVT with usual care for acute ischemic stroke due to anterior circulation large vessel occlusion. Good functional outcome, defined as modified Rankin Scale score 0 to 2 at 90 days, was compared between randomized patients with and without CTP baseline imaging. Univariable and multivariable binary logistic regression analysis was performed to determine the association of baseline CTP imaging and good functional outcome. RESULTS: We analyzed 1348 patients 610 (45.3%) of whom underwent CTP prerandomization. The benefit of EVT compared with best medical management was maintained irrespective of the baseline imaging paradigm (90-day modified Rankin Scale score 0-2 in EVT versus control patients: with CTP: 46.0% (137/298) versus 28.9% (88/305), without CTP: 44.1% (162/367) versus 27.3% (100/366). Performance of CTP baseline imaging compared with baseline noncontrast CT and CT angiography only yielded similar rates of good outcome (odds ratio, 1.05 [95% CI, 0.82-1.33], adjusted odds ratio, 1.04, [95% CI, 0.80-1.35]). CONCLUSIONS: Rates of good functional outcome were similar among patients in whom CTP was or was not performed, and EVT treatment effect in the 0- to 6-hour time window was similar in patients with and without baseline CTP imaging.

Evaluating the Diagnostic Performance of Prehospital Stroke Scales Across the Range of Deficit Severity: Analysis of the Prehospital Triage of Patients With Suspected Stroke Study.

BACKGROUND: The usefulness of prehospital scales for identifying anterior circulation large vessel occlusion (aLVO) in patients with suspected stroke may vary depending on the severity of their presentation. The performance of these scales across the spectrum of deficit severity is unclear. The aim of this study was to evaluate the diagnostic performance of 8 prehospital scales for identifying aLVO across the spectrum of deficit severity. METHODS: We used data from the PRESTO study (Prehospital Triage of Patients With Suspected Stroke Symptoms), a prospective observational study comparing prehospital stroke scales in detecting aLVO in suspected stroke patients. We used the National Institutes of Health Stroke Scale (NIHSS) score, assessed in-hospital, as a proxy for the Clinical Global Impression of stroke severity during prehospital assessment by paramedics. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and the difference in aLVO probabilities with a positive or negative prehospital scale test (ΔPaLVO) for each scale for mild (NIHSS 0-4), intermediate (NIHSS 5-9), moderate (NIHSS 10-14), and severe deficits (NIHSS≥15). RESULTS: Among 1033 patients with suspected stroke, 119 (11.5%) had an aLVO, of whom 19 (16.0%) had mild, 25 (21.0%) had intermediate, 30 (25.2%) had moderate, and 45 (37.8%) had severe deficits. The scales had low sensitivity and positive predictive value in patients with mild-intermediate deficits, and poor specificity, negative predictive value, and accuracy with moderate-severe deficits. Positive results achieved the highest ΔPaLVO in patients with mild deficits. Negative results achieved the highest ΔPaLVO with severe deficits, but the probability of aLVO with a negative result in the severe range was higher than with a positive test in the mild range. CONCLUSIONS: Commonly-used prehospital stroke scales show variable performance across the range of deficit severity. Probability of aLVO remains high with a negative test in severely affected patients. Studies reporting prehospital stroke scale performance should be appraised in the context of the NIHSS distribution of their samples.

CT Hyperdense Artery Sign and the Effect of Alteplase in Endovascular Thrombectomy after Acute Stroke.

Background Recent evidence suggests that presence of an intracranial arterial thrombus with a hyperdense artery sign (HAS) at noncontrast CT (NCCT) is associated with better response to intravenous alteplase. Patients with HAS may benefit more from combined intravenous alteplase and endovascular treatment (EVT). Purpose To investigate whether HAS at NCCT modifies the treatment effect of adding intravenous alteplase on clinical outcome in patients with acute large-vessel occlusion undergoing EVT. Materials and Methods This study is a secondary analysis of a prospective randomized trial (Direct Intra-arterial thrombectomy in order to Revascularize AIS patients with large-vessel occlusion Efficiently in Chinese Tertiary hospitals: A Multicenter randomized clinical Trial [DIRECT-MT]), which compared adding alteplase to EVT versus EVT alone in participants with acute large-vessel occlusion between February 2018 and July 2019. Participants with catheter angiograms and adequate NCCT for HAS evaluation were included. HAS was determined visually by two independent investigators at baseline NCCT. Treatment effect of intravenous alteplase administration according to presence of HAS on the primary clinical outcome (modified Rankin Scale [mRS] score at 90 days) and secondary and safety outcomes were assessed using adjusted multivariable regression models. Results Among 633 included participants (356 men [56%]; median age, 69 years), HAS was observed in 283 participants (45%): 142 of 313 participants (45%) in the EVT-only group and 141 of 320 participants (44%) in the group with added intravenous alteplase. Treatment-by-HAS interaction was observed for the primary outcome (P < .001), whereby a shift in favor of better outcomes with added intravenous alteplase occurred in participants with HAS (adjusted odds ratio [OR]: 1.82; 95% CI: 1.18, 2.79), while an adverse effect was seen in participants without HAS (adjusted OR: 0.62; 95% CI: 0.42, 0.91). This also held true for three secondary outcomes (excellent outcome [mRS score of 0-1 at 90 days], P = .005; good outcome [mRS score of 0-2 at 90 days], P = .008; final successful reperfusion, P = .04) in the adjusted models. Conclusion After acute ischemic stroke, presence of hyperdense artery sign (HAS) at baseline noncontrast CT indicated better outcomes when alteplase was added to endovascular treatment, but adding alteplase to endovascular treatment resulted in worse outcomes in participants without HAS. Clinical trial registration no. NCT03469206 © RSNA, 2022 Online supplemental material is available for this article.

Acute ischaemic stroke associated with SARS-CoV-2 infection in North America.

BACKGROUND: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age >60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p<0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. CONCLUSION: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality.