Control-matched octo/nonagenarian outcomes in acute basilar artery occlusions treated with mechanical thrombectomy-analysis of the PC-SEARCH thrombectomy registry.

INTRODUCTION: Age is often used as a predictor in determining outcomes in large vessel occlusions treated with mechanical thrombectomy. However, limited data exist for octo/nonagenarian outcomes compared to younger individuals in acute basilar artery occlusions treated with thrombectomy. METHODS: Patient data were obtained from the PC-SEARCH Thrombectomy Registry which consists of 444 acute basilar artery occlusions treated with mechanical thrombectomy. Individuals were dichotomized based on age (>80 and ≤80 years old). Primary outcome was defined as modified Rankin Scale of 0-3 at 90 days. Logistic and multivariate regression, as well as control-matched analysis, were performed. RESULTS: There were 373 and 71 patients in the younger and older cohorts, respectively. Gender, ethnicity, smoking status, atrial fibrillation, and coronary artery disease were noted to be significantly different between cohorts. At 90 days, 178 (47.7%) and 23 (32.4%) patients achieved primary outcome at 90 days (p = 0.02), however, after controlling for potentially confounding factors this association lost significance (OR 0.50 95% CI 0.24-1.05; p = 0.07). There were 84 patients included in the control matched analysis and demonstrated no significant differences on multivariate analysis between cohorts (OR 0.68 95% CI 0.25-1.84; p = 0.45). INTERPRETATION: Octa/nonagenarians presenting with an acute basilar artery occlusion treated with mechanical thrombectomy can achieve acceptable rates of favorable functional outcomes compared to younger individuals with similar baseline demographic and stroke characteristics.

A single-cell atlas deconstructs heterogeneity across multiple models in murine traumatic brain injury and identifies novel cell-specific targets.

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution. We identify cell-specific targets and previously unrecognized roles for microglial and ependymal subtypes. Ependymal-4 was a hub of neuroinflammatory signaling. A distinct microglial lineage shared features with disease-associated microglia at 24 h, with persistent gene-expression changes in microglia-4 even 6 months after contusional TBI, contrasting all other cell types that mostly returned to naive levels. Regional and sexual dimorphism were noted. CEREBRI, our searchable atlas (https://shiny.crc.pitt.edu/cerebri/), identifies previously unrecognized cell subtypes/molecular targets and is a leverageable platform for future efforts in TBI and other diseases with overlapping pathophysiology.

Thrombectomy Outcomes in Acute Basilar Artery Occlusions Due to Intracranial Atherosclerotic Disease.

BACKGROUND AND OBJECTIVES: Intracranial atherosclerotic disease (ICAD) large vessel occlusion (LVO) is responsible for up to 30% of LVO. In this study, we aimed to determine the likelihood of favorable functional outcomes (modified Rankin Scale 0-3) in acute ICAD-LVO basilar occlusion compared with embolic basilar occlusion. METHODS: This is an analysis of the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intraprocedural Predictors for Mechanical Thrombectomy Registry in which patients with acute basilar artery occlusions from 8 comprehensive stroke centers were included from 2015 to 2021. Patients were dichotomized into with (ICAD-LVO) or without underlying ICAD (embolic). Descriptive statistics for each group and multivariate logistic analysis were performed on the primary outcome. RESULTS: Three hundred forty-six patients were included. There were 215 patients with embolic (62%) and 131 patients with ICAD-LVO (38%). Baseline demographics were equivalent between the 2 groups except for sex (male 47% vs 67%; P < .001), history of stroke (12% vs 25%; P = .002), and atrial fibrillation (31% vs 17%; P = .003). At 90 days, patients in the ICAD-LVO cohort were less likely to achieve favorable functional outcomes (odds ratio [OR] 0.41, 95% CI 0.22-0.72; P = .003) after adjusting for potentially confounding factors. In addition, ICAD-LVO strokes were less likely to achieve thrombolysis in cerebral infarction ≥2b (OR 0.29, 95% CI 0.14-0.57; P < .001). ICAD-LVO lesions were more likely to require stent placement (OR 14.94, 95% CI 4.91-45.49; P < .001). Subgroup analysis demonstrated favorable functional outcomes in patients who underwent stenting and angioplasty compared with failed recanalization cohort (OR 4.96, 95% CI 1.68-14.64; P < .004). CONCLUSION: Patients with acute basilar ICAD-LVO have higher morbidity and mortality compared with patients with embolic source. Lower rates of successful recanalization in the ICAD-LVO cohort support this finding. Our subgroup analysis demonstrates that stenting should be considered in patients with recanalization failure. Rates of symptomatic intracranial hemorrhage were similar between the ICAD-LVO and embolic cohorts.

Endovascular therapy of isolated posterior cerebral artery occlusion stroke with and without general anesthesia.

BACKGROUND: The optimal anesthetic strategy for endovascular therapy (EVT) in acute ischemic stroke is still under debate. The aim of this study was to compare the clinical outcomes of patients with isolated posterior cerebral artery (PCA) occlusion stroke undergoing EVT by anesthesia modality with conscious sedation (non-GA) versus general anesthesia (GA). METHODS: Patients from the Posterior CerebraL Artery Occlusion (PLATO) study were analyzed with regard to anesthetic strategy. GA was compared with non-GA using multivariable logistic regression and inverse probability of weighting treatment (IPTW) methods. The primary endpoint was the 90-day distribution of the modified Rankin Scale (mRS) score. Secondary outcomes included functional independence or return to Rankin at day 90, and successful reperfusion, defined as expanded Thrombolysis in Cerebral Infarction (eTICI) 2b to 3. Safety endpoints were symptomatic intracranial hemorrhage and mortality. RESULTS: Among 376 patients with isolated PCA occlusion stroke treated with EVT, 183 (49%) had GA. The treatment groups were comparable, although the GA group contained more patients with severe stroke and lower posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS). On IPTW analysis, there was no difference between groups with regard to ordinal mRS shift analysis (common OR 0.89, 95% CI 0.53 to 1.51, P=0.67) or functional independence (OR 0.84, 95% CI 0.50 to 1.39, P=0.49). There were greater odds for successful reperfusion with GA (OR 1.70, 95% CI 1.17 to 2.47, P=0.01). Safety outcomes were comparable between groups. CONCLUSION: In patients with isolated PCA occlusion undergoing EVT, patients treated with GA had higher reperfusion rates compared with non-GA. Both GA and non-GA strategies were safe and functional outcomes were similar.

Predictors of outcome and symptomatic intracranial hemorrhage in acute basilar artery occlusions: Analysis of the PC-SEARCH thrombectomy registry.

INTRODUCTION: Recent randomized controlled trials demonstrated superiority of mechanical thrombectomy compared to medical therapy in acute basilar artery occlusions, however, little data is available to guide clinicians in functional prognosis and risk stratification. PATIENTS AND METHODS: Data from the retrospectively established PC-SEARCH Thrombectomy registry, which included patients with basilar artery occlusion from eight sites from January 2015 to December 2021, was interrogated. Outcomes were dichotomized into 90-day favorable (mRS ⩽ 3) and unfavorable (mRS > 3). Multivariate logistic regression analysis was performed with respect to the outcome groups and were adjusted for potential confounding baseline characteristics. RESULTS: Four-hundred-forty-four patients were included in this analysis. Mean age was 66 [SD 15], with 56% male, and comprised of 76% Caucasian. Patients presented with an initial median NIHSS of 18 and 199 patients (44.8%) achieved favorable 90-day functional outcomes. Independent predictors of favorable outcomes included younger age, pc-ASPECTS > 8 (OR 2.30 p < 0.001), and TICI ⩾ 2b (OR 7.56 p < 0.001). Unfavorable outcomes were associated with increasing number of passes (OR 1.29 p = 0.004) and sICH (OR 4.19 p = 0.015). IA-tPA was an independent risk factor for sICH (OR 7.15 p = 0.002) without improving favorable functional outcomes. CONCLUSION AND DISCUSSION: PC-ASPECTS > 8, successful recanalization (TICI ⩾ 2b), first-pass recanalization, and younger age are independent predictors of favorable 90-day functional outcome in thrombectomy treated patients with acute basilar artery occlusion. Conversely, sICH were independent predictors of unfavorable outcomes. IA-tPA and unsuccessful recanalization are independently associated with sICH.

Early and late basilar artery thrombectomy time window outcomes.

Importance: Stroke-to-recanalization time is a strong predictor of outcomes in anterior circulation large-vessel occlusion (LVO). The authors aimed to evaluate functional outcomes in early (<6 h) vs. late (6-24 h) time windows for thrombectomy-treated basilar artery occlusions. Methods: Patients were derived from the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intra-procedural Predictors of Mechanical Thrombectomy (PC-SEARCH) Registry and retrospectively analyzed early and late basilar artery thrombectomy time windows cohorts. Patients were dichotomized based on the last known well and correlated to 90-day functional outcomes (mRS 0-3). A multiple logistic regression analysis was performed. Results: A total of 405 patients were included in this study: 216 and 189 patients in the early and late time windows, respectively. Baseline demographic, stroke, radiographic, and intraprocedural characteristics were similar between the groups. A total of 99 (46%) and 79 (42%) patients in the early and late time windows, respectively, achieved favorable functional outcomes at 90 days (p = 0.41), and multiple logistic regression analysis did not reveal differences between cohorts (OR: 0.74; 95% CI: 0.46-1.19; p = 0.22). Symptomatic hemorrhage (7% vs. 5%; p = 0.69) and neurological complications (8% vs. 9%; p = 0.83) were similar between the groups; however, hospital complications were more common in the early time window cohort (22% vs. 13%; p = 0.01). Conclusion: The early and late thrombectomy time windows can achieve similar rates of 90-day favorable functional outcomes. However, timely thrombectomy influences the likelihood of achieving excellent functional outcomes (mRS ≤ 2) within the early time window.

Comparing Functional Outcomes and Safety Profiles of First-Line Aspiration Thrombectomy Versus Stentriever for Acute Basilar Artery Occlusion: Propensity Analysis of the PC-SEARCH Thrombectomy Registry.

BACKGROUND: Aspiration catheters (ASPs) and stentriever thrombectomy devices have comparable safety and efficacy in anterior circulation ischemic strokes. However, there is lack of high-quality comparative data in acute basilar artery occlusions. Our objective is to compare the outcomes and safety of ASPs and stentriever devices in acute basilar artery occlusions. METHODS: This is an analysis of the retrospectively established PC-SEARCH Thrombectomy (Posterior-Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intraprocedural Predictors for Mechanical Thrombectomy) registry. Patients were dichotomized based on their first-line thrombectomy device (ASP and stentriever) and associated with their 90-day functional outcomes, intraprocedural metrics, and safety measures. Propensity analysis based on unequal baseline characteristics was performed. Consecutive patients with acute basilar artery occlusions who received mechanical thrombectomy were included from January 2015 to December 2021. Patients received either first-line contact aspiration or stentriever mechanical thrombectomy. Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale score of 0 to 3 and symptomatic intracranial hemorrhage, respectively. Secondary outcomes included puncture-recanalization times, first-pass recanalization rates, crossovers to other thrombectomy device, and neurological/hospital complications. RESULTS: Five hundred eighteen patients were included in the registry, and a total of 383 patients were included (mean [SD] age, 65.5 [15] years; 228 [59%] men) in this analysis. Of these, 219 patients were first-line ASP while 164 patients received first-line stentriever devices. Median premorbid modified Rankin Scale was zero and median presenting National Institutes of Health Stroke Scale was 17 (interquartile range, 8-26). The proportion of favorable functional outcome was similar between the 2 techniques before (47.3% versus 42.5%; odds ratio, 1.22 [95% CI, 0.78-1.89]; P=0.38) and after propensity matching (odds ratio, 1.46 [95% CI, 0.85-2.49]; P=0.17). In our propensity-matched cohorts, puncture-recanalization times (18 versus 52 minutes; P<0.01) favored first-line ASP; however, first-pass recanalization rates (43.5% versus 44.5%; P=0.90) were similar between groups. First-line ASP was associated with higher rates of crossover (22% versus 6%; P<0.01), whereas stentriever was associated with higher rates of symptomatic intracranial hemorrhage (9.8% versus 3.4%; P=0.04). CONCLUSIONS: First-line ASP and stentriever methods demonstrated similar functional outcome and recanalization rates. Stentriever methods were associated with higher rates of symptomatic intracranial hemorrhage, whereas ASPs were associated with higher rates of crossover to alternative technique in patients with acute basilar occlusions.

Cerebrospinal Fluid Biomarkers for Diagnosis and the Prognostication of Acute Ischemic Stroke: A Systematic Review.

Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.

Global, Regional, and National Economic Consequences of Stroke.

BACKGROUND: An understanding of global, regional, and national macroeconomic losses caused by stroke is important for allocation of clinical and research resources. The authors investigated the macroeconomic consequences of stroke disease burden in the year 2019 in 173 countries. METHODS: Disability-adjusted life year data for overall stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) were collected from the GBD study (Global Burden of Disease) 2019 database. Gross domestic product (GDP, adjusted for purchasing power parity [PPP]) data were collected from the World Bank; GDP and disability-adjusted life year data were combined to estimate macroeconomic losses using a value of lost welfare (VLW) approach. All results are presented in 2017 international US dollars adjusted for PPP. RESULTS: Globally, in 2019, VLW due to stroke was $2059.67 billion or 1.66% of the global GDP. Global VLW/GDP for stroke subtypes was 0.78% (VLW=$964.51 billion) for ischemic stroke, 0.71% (VLW=$882.81 billion) for intracerebral hemorrhage, and 0.17% (VLW=$212.36 billion) for subarachnoid hemorrhage. The Central European, Eastern European, and Central Asian GBD super-region reported the highest VLW/GDP for stroke overall (3.01%), ischemic stroke (1.86%), and for subarachnoid hemorrhage (0.26%). The Southeast Asian, East Asian, and Oceanian GBD super-region reported the highest VLW/GDP for intracerebral hemorrhage (1.48%). CONCLUSIONS: The global macroeconomic consequences related to stroke are vast even when considering stroke subtypes. The present quantification may be leveraged to help justify increased spending of finite resources on stroke in an effort to improve outcomes for patients with stroke globally.

Endovascular Versus Medical Management of Posterior Cerebral Artery Occlusion Stroke: The PLATO Study.

BACKGROUND: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. METHODS: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. RESULTS: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P=0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P=0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P=0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P=0.0001; mortality, 10.1% versus 5.0%; P=0.002). CONCLUSIONS: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.

Real-World Outcomes of Endovascular Thrombectomy for Basilar Artery Occlusion: Results of the BArONIS Study.

OBJECTIVE: To evaluate clinical outcomes of endovascular thrombectomy (EVT) for acute basilar artery occlusion (BAO) using population-level data from the United States. METHODS: Weighted discharge data from the National Inpatient Sample were queried to identify adult patients with acute BAO during the period of 2015 to 2019 treated with EVT or medical management only. Complex samples statistical methods and propensity-score adjustment using inverse probability of treatment weighting (IPTW) were performed to assess clinical endpoints. RESULTS: Among 3,950 BAO patients identified, 1,425 (36.1%) were treated with EVT [mean age 66.7 years, median National Institute of Health Stroke Scale (NIHSS) score 22]. On unadjusted analysis, 155 (10.9%) EVT patients achieved favorable functional outcomes (discharge disposition to home without services), while 515 (36.1%) experienced in-hospital mortality, and 20 (1.4%) developed symptomatic intracranial hemorrhage (sICH). Following propensity-score adjustment by IPTW accounting for age, stroke severity, and comorbidity burden, EVT was independently associated with favorable functional outcome [adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07, 1.46; p = 0.004], but not with in-hospital mortality or sICH. In an IPTW-adjusted sub-group analysis of patients with NIHSS scores >20, EVT was associated with both favorable functional outcome (discharge disposition to home or to acute rehabilitation) (aOR 1.55, 95% CI 1.24, 1.94; p < 0.001) and decreased mortality (aOR 0.78, 95% CI 0.69, 0.89; p < 0.001), but not with sICH. INTERPRETATION: This retrospective population-based analysis using a large national registry provides real-world evidence of a potential benefit of EVT in acute BAO patients. ANN NEUROL 2023;94:55-60.

Mechanical Thrombectomy Global Access For Stroke (MT-GLASS): A Mission Thrombectomy (MT-2020 Plus) Study.

BACKGROUND: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. METHODS: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. RESULTS: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70-11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower-middle versus high: odds ratio, 0.08 [95% CI, 0.04-0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07-5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84-4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70-9.42]) were significantly associated with increased odds of MTA. CONCLUSIONS: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country's per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

Factors associated with readmission after minimally invasive transforaminal lumbar interbody fusion.

OBJECTIVE: The objective of this study was to identify factors that lead to a prolonged hospital stay or 30-day readmission after minimally invasive surgery (MIS) for transforaminal lumbar interbody fusion (TLIF) at a single institution. METHODS: Consecutive patients who underwent MIS TLIF from January 1, 2016, to March 31, 2018, were retrospectively analyzed. Demographic data, including age, sex, ethnicity, smoking status, and body mass index, were collected along with operative details, indications, affected spinal levels, estimated blood loss, and operative duration. The effects of these data were evaluated relative to the hospital length of stay (LOS) and 30-day readmission. RESULTS: The authors identified 174 consecutive patients who underwent MIS TLIF at 1 or 2 levels from a prospectively collected database. The mean (range) patient age was 64.1 (31-81) years, 97 were women (56%), and 77 were men (44%). Of 182 levels fused, 127 were done at L4-5 (70%), 32 at L3-4 (18%), 13 at L5-S1 (7%), and 10 at L2-3 (5%). Patients underwent 166 (95%) single-level procedures and 8 (5%) 2-level procedures. The mean (range) procedural duration, defined as the time from incision to closure, was 164.6 (90-529) minutes. The mean (range) LOS was 1.8 (0-8) days. Eleven patients (6%) were readmitted within 30 days; the most frequent causes were urinary retention, constipation, and persistent or contralateral symptoms. Seventeen patients had LOS greater than 3 days. Six of those patients (35%) were identified as widows, widowers, or divorced, and 5 of them lived alone. Six patients with prolonged LOS (35%) required placement in either skilled nursing or acute inpatient rehabilitation. Regression analyses showed living alone (p = 0.04) and diabetes (p = 0.04) as predictors of readmission. Regression analyses revealed female sex (p = 0.03), diabetes (p = 0.03), and multilevel surgery (p = 0.006) as predictors of LOS > 3 days. CONCLUSIONS: Urinary retention, constipation, and persistent radicular symptoms were the leading causes of readmission within 30 days of surgery in this series, which is distinct from data from the American College of Surgeons National Surgical Quality Improvement Program. The inability to discharge a patient home for social reasons led to prolonged inpatient hospital stays. Identifying these risk factors and proactively addressing them could lower readmission rates and decrease LOS among patients undergoing MIS TLIF.

Direct Transfer to the Neuroangiography Suite for Patients With Stroke.

The therapeutic focus in acute ischemic stroke over the last 2.5 decades has been to balance the benefits of rapid reperfusion therapy with the risks of treatment-related complications. Both intravenous thrombolytics and endovascular thrombectomy are proven to substantially improve outcomes in a time-dependent manner. Each minute saved in achieving successful reperfusion grants an additional week of healthy life and may salvage up to 27 million neurons. The current approach to patient triage is inherited from the preendovascular thrombectomy era of stroke care. Current workflow concentrates on stabilization, diagnosis, and decision-making in the emergency department, followed by thrombolysis if eligible and subsequent transfer to the angiography suite as needed for further treatment. Multiple efforts have been directed toward minimizing the time from first medical contact to reperfusion therapy including prehospital triage and intrahospital workflow. Novel approaches for stroke patient triage such as the direct to angio approach, (also referred to as One Stop Management) are currently in development. The concept was initially introduced as several single-center experiences. In this narrative review article, we will consider various definitions of direct to angio and its variants, discuss its rationale, review its safety and efficacy, assess its feasibility, and delineate its limitations. Further, we will address methods to overcome these limitations and the potential impact of emerging data and new technologies on the direct-to-angio approach.

Precision Effects of Glibenclamide on MRI Endophenotypes in Clinically Relevant Murine Traumatic Brain Injury.

OBJECTIVES: Addressing traumatic brain injury (TBI) heterogeneity is increasingly recognized as essential for therapy translation given the long history of failed clinical trials. We evaluated differential effects of a promising treatment (glibenclamide) based on dose, TBI type (patient selection), and imaging endophenotype (outcome selection). Our goal to inform TBI precision medicine is contextually timely given ongoing phase 2/planned phase 3 trials of glibenclamide in brain contusion. DESIGN: Blinded randomized controlled preclinical trial of glibenclamide on MRI endophenotypes in two established severe TBI models: controlled cortical impact (CCI, isolated brain contusion) and CCI+hemorrhagic shock (HS, clinically common second insult). SETTING: Preclinical laboratory. SUBJECTS: Adult male C57BL/6J mice (n = 54). INTERVENTIONS: Mice were randomized to naïve, CCI±HS with vehicle/low-dose (20 µg/kg)/high-dose glibenclamide (10 µg/mouse). Seven-day subcutaneous infusions (0.4 µg/hr) were continued. MEASUREMENTS AND MAIN RESULTS: Serial MRI (3 hr, 6 hr, 24 hr, and 7 d) measured hematoma and edema volumes, T2 relaxation (vasogenic edema), apparent diffusion coefficient (ADC, cellular/cytotoxic edema), and 7-day T1-post gadolinium values (blood-brain-barrier [BBB] integrity). Linear mixed models assessed temporal changes. Marked heterogeneity was observed between CCI versus CCI+HS in terms of different MRI edema endophenotypes generated (all p < 0.05). Glibenclamide had variable impact. High-dose glibenclamide reduced hematoma volume ~60% after CCI (p = 0.0001) and ~48% after CCI+HS (p = 4.1 × 10-6) versus vehicle. Antiedema benefits were primarily in CCI: high-dose glibenclamide normalized several MRI endophenotypes in ipsilateral cortex (all p < 0.05, hematoma volume, T2, ADC, and T1-post contrast). Acute effects (3 hr) were specific to hematoma (p = 0.001) and cytotoxic edema reduction (p = 0.0045). High-dose glibenclamide reduced hematoma volume after TBI with concomitant HS, but antiedema effects were not robust. Low-dose glibenclamide was not beneficial. CONCLUSIONS: High-dose glibenclamide benefitted hematoma volume, vasogenic edema, cytotoxic edema, and BBB integrity after isolated brain contusion. Hematoma and cytotoxic edema effects were acute; longer treatment windows may be possible for vasogenic edema. Our findings provide new insights to inform interpretation of ongoing trials as well as precision design (dose, sample size estimation, patient selection, outcome selection, and Bayesian analysis) of future TBI trials of glibenclamide.

Utility of tPA Administration in Acute Treatment of Internal Carotid Artery Occlusions.

Background: Intravenous tissue plasminogen activator (IV-tPA) remains part of the guidelines for acute ischemic stroke treatment, yet internal carotid artery occlusions (ICAO) are known to be poorly responsive to IV-tPA. It is unknown whether bridging thrombolysis (BT) is beneficial in such cases. Purpose: We sought to evaluate whether the use of IV-tPA improved overall clinical outcomes in patients undergoing endovascular thrombectomy (EVT) for ICA occlusions. Methods: Data from 1367 consecutive stroke cases treated with EVT from 2012-2019 were prospectively collected from a single center. Univariate and multivariate logistic regression were used to assess the relationship between IV-tPA administration and clinical outcome. Results: 153 patients were found to have carotid terminus and tandem ICAO who received EVT and presented within 4.5h of last seen well. 50% (n = 82) received IV tPA. There were no differences between the groups with respect to age, NIHSS, time to EVT and ASPECTS score. 53% had tandem ICA-MCA occlusions. Rate of recanalization (≥ TICI 2B) and sICH did not significantly differ between the two groups. Regression analysis demonstrated no effect of IV-tPA on modified Rankin Score (mRS) at 90 days and overall mortality. Factors significantly associated with reduced mortality included lower age, lower NIHSS, and better rate of recanalization. Conclusions: There was no significant difference in clinical outcomes in those receiving BT vs. direct EVT for ICAO. For centers with optimal door-to-puncture times, bypassing IV-tPA may expedite recanalization times and potentially yield more favorable outcomes. Patients with higher NIHSS and tandem lesions may have better outcomes with BT.

Delayed Functional Independence After Neurothrombectomy (DEFIANT) score: analysis of the Trevo Retriever Registry.

BACKGROUND: Chronological heterogeneity in neurological improvement after endovascular thrombectomy (EVT) for large vessel occlusion (LVO) stroke is commonly observed in clinical practice. Understanding the temporal progression of functional independence after EVT, especially delayed functional independence in patients who do not improve early, is essential for prognostication and rehabilitation. We aim to determine the incidence of early functional independence (EFI) and delayed functional independence (DFI), identify associated predictors after EVT, and develop the Delayed Functional Independence After Neurothrombectomy (DEFIANT) score. METHODS: Demographic, clinical, radiological, treatment, and procedural information were analyzed from the Trevo Registry (patients undergoing EVT due to anterior LVO using the Trevo stent retriever). Incidence and predictors of EFI (modified Rankin Scale (mRS) score 0-2 at discharge) and DFI (mRS score 0-2 at 90 days in non-EFI patients) were analyzed. RESULTS: A total of 1623 patients met study criteria. EFI was observed in 45% (730) of patients. Among surviving non-EFI patients (884), DFI was observed in 35% (308). Younger age (p=0.003), lower discharge National Institutes of Health Stroke Scale (NIHSS) score (p<0.0001), and absence of any hemorrhage (p=0.021) were independent predictors of DFI. After age 60, the probability of DFI declines significantly with 5 year age increments (approximately 7% decline for every 5 years; p(DFI)= 1.3559-0.0699, p for slope=0.001). The DEFIANT score is available online (https://bit.ly/3KZRVq5). CONCLUSION: Approximately 45% of patients experience EFI. About one-third of non-early improvers experience DFI. Younger age, lower discharge NIHSS score, and absence of any hemorrhage were independent predictors of DFI among non-early improvers.

Endovascular Therapy vs Medical Management for Patients With Acute Stroke With Medium Vessel Occlusion in the Anterior Circulation.

Importance: Randomized clinical trials have shown the efficacy of endovascular therapy (EVT) for acute large vessel occlusion strokes. The benefit of EVT in acute stroke with distal, medium vessel occlusion (DMVO) remains unclear. Objective: To examine the efficacy and safety outcomes associated with EVT in patients with primary DMVO stroke when compared with a control cohort treated with medical management (MM) alone. Design, Setting, and Participants: This multicenter, retrospective cohort study pooled data from patients who had an acute stroke and a primary anterior circulation emergency DMVO, defined as any segment of the anterior cerebral artery (ACA) or distal middle cerebral artery, between January 1, 2015, and December 31, 2019. Those with a concomitant proximal occlusion were excluded. Outcomes were compared between the 2 treatment groups using propensity score methods. Data analysis was performed from March to June 2021. Exposures: Patients were divided into EVT and MM groups. Main Outcomes and Measures: Main efficacy outcomes included 3-month functional independence (modified Rankin Scale [mRS] scores, 0-2) and 3-month excellent outcome (mRS scores, 0-1). Safety outcomes included 3-month mortality and symptomatic intracranial hemorrhage. Results: A total of 286 patients with DMVO were evaluated, including 156 treated with EVT (mean [SD] age, 66.7 [13.7] years; 90 men [57.6%]; median National Institute of Health Stroke Scale [NIHSS] score, 13.5 [IQR, 8.5-18.5]; intravenous tissue plasminogen activator [IV tPA] use, 75 [49.7%]; ACA involvement, 49 [31.4%]) and 130 treated with medical management (mean [SD] age, 69.8 [14.9] years; 62 men [47.7%]; median NIHSS score, 7.0 [IQR, 4.0-14.0], IV tPA use, 58 [44.6%]; ACA involvement, 31 [24.0%]). There was no difference in the unadjusted rate of 3-month functional independence in the EVT vs MM groups (151 [51.7%] vs 124 [50.0%]; P = .78), excellent outcome (151 [38.4%] vs 123 [31.7%]; P = .25), or mortality (139 [18.7%] vs 106 [11.3%]; P = .15). The rate of symptomatic intracranial hemorrhage was similar in the EVT vs MM groups (weighted: 4.0% vs 3.1%; P = .90). In inverse probability of treatment weighting propensity analyses, there was no significant difference between groups for functional independence (adjusted odds ratio [aOR], 1.36; 95% CI, 0.84-2.19; P = .20) or mortality (aOR, 1.24; 95% CI, 0.63-2.43; P = .53), whereas the EVT group had higher odds of an excellent outcome (mRS scores, 0-1) at 3 months (aOR, 1.71; 95% CI, 1.02-2.87; P = .04). Conclusions and Relevance: The findings of this multicenter cohort study suggest that EVT may be considered for selected patients with ACA or distal middle cerebral artery strokes. Further larger randomized investigation regarding the risk-benefit ratio for DMVO treatment is indicated.

Predictors of first pass effect and effect on outcomes in mechanical thrombectomy for basilar artery occlusion.

INTRODUCTION: For patients undergoing endovascular thrombectomy (EVT), those who are recanalized with a successful single pass (first pass effect, FPE) have better functional outcomes than those who do not. There is a scarcity of data regarding predictors of FPE in basilar artery occlusion (BAO). We aim to determine what characteristics may predict FPE for posterior circulation thrombectomies in a cohort of patients undergoing EVT for BAO. METHODS: We reviewed prospectively-collected data for patients presenting to a comprehensive stroke center with BAO between December 2015 and April 2019. Patients were included in this study if they underwent manual aspiration thrombectomy for BAO. Patients were excluded if they had occlusions of the posterior cerebral or vertebral arteries or if they had tandem lesions. Patients were stratified by whether FPE or modified FPE (mFPE) was achieved, and multivariate logistic regression analyses were performed to identify predictors of FPE and the effect of FPE on clinical outcome. RESULTS: 100 patients with BAO underwent thrombectomy. Mean age was 64.7 ± 16.7, 42% were female, and median NIHSS was 20 (IQR 11-27). 33% met criteria for FPE and 60% for mFPE. Univariate analysis identified female gender, lack of IV-tPA use, pcASPECTS, atrial fibrillation, and hyperlipidemia as possible predictors of FPE. On multivariate analysis, age, pcASPECTs, atrial fibrillation, hyperlipidemia and IV-tPA use were not independent predictors of FPE or mFPE. Female gender was an independent predictor of mFPE (p = 0.02), but not FPE (p = 0.18). FPE was a predictor of mRS 0-2 at 90 days (p = 0.04). Predictors of mortality were age (p < 0.01), baseline NIHSS (p < 0.01) and mFPE (p = 0.01). CONCLUSION: In this cohort analysis of 100 patients with basilar artery occlusion undergoing manual aspiration thrombectomy, female gender was associated with mFPE but not FPE. Previously-reported anterior circulation FPE predictors including age, ASPECTS and atrial fibrillation were not predictors of FPE in this cohort of patients with BAO.

Expedited Management of Low-Risk Transient Ischemic Attack Patients: The "Fast-Track" TIA Protocol.

OBJECTIVES: Transient ischemic attack (TIA) serves a precursor for an acute ischemic stroke (AIS); however, not all TIA patients harbor the same risk for subsequent AIS. We aimed to investigate expediting outpatient management of low-risk TIA patients (ABCD: Giles and Rothwell, 2007 score ≤ 3) via our "Fast-Track" TIA Protocol (FTTP). MATERIALS AND METHODS: A retrospective analysis was performed on patients who presented to our academic network 04/2020 - 2/2021. Patients who presented with ABCD: Giles and Rothwell, 2007 scores ≤ 3 without large vessel occlusion or flow limiting stenosis were eligible for the FTTP. These patients were discharged on dual antiplatelet therapy and statin and received prescriptions for transthoracic echo, holter monitor, LDL, and A1c along with a scheduled follow-up appointment 30 days from presentation. RESULTS: 182 consecutive patients were evaluated during this period, 21 (11%) were excluded from analysis due to NIHSS > 0 and/or infarct present on MRI. 35 (22%) patients qualified for FTTP and were directly discharged from the ED. Median ABCD2 score was 2 for the discharge group and 4 for the admitted group. There was a significant difference with respect to age and hypertension. Additionally, the FTTP patient population were more likely to be smokers than the admitted patient population. 3 FTTP patients re-presented to the ED, but none of them suffered a symptomatic stroke. CONCLUSIONS: A FTTP demonstrated feasibility and safety with low rates of re-presentation and ischemic stroke. Further research is warranted to determine an optimal patient population that can be safely managed in an outpatient setting.