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OBJECTIVE Acute ischemic stroke patients with large-vessel occlusion and good collateral blood flow have significantly better outcomes than patients with poor collateral circulation. The purpose of this study was to evaluate the cost-effectiveness of endovascular thrombectomy (EVT) based on collateral status and, in particular, to analyze its effectiveness in ischemic stroke patients with poor collaterals. METHODS A decision analysis study was performed with Markov modeling to estimate the lifetime quality-adjusted life-years (QALYs) and associated costs of EVT based on collateral status. The study was performed over a lifetime horizon with a societal perspective in the US setting. Base-case analysis was done for good, intermediate, and poor collateral status. One-way, two-way, and probabilistic sensitivity analyses were performed. RESULTS EVT resulted in greater effectiveness of treatment compared to no EVT/medical therapy (2.56 QALYs in patients with good collaterals, 1.88 QALYs in those with intermediate collaterals, and 1.79 QALYs in patients with poor collaterals), which was equivalent to 1050, 771, and 734 days, respectively, in a health state characterized by a modified Rankin Scale (mRS) score of 0–2. EVT also resulted in lower costs in patients with good and intermediate collaterals. For patients with poor collateral status, the EVT strategy had higher effectiveness and higher costs, with an incremental cost-effectiveness ratio (ICER) of $44,326/QALY. EVT was more cost-effective as long as it had better outcomes in absolute numbers in at least 4%–8% more patients than medical management. CONCLUSIONS EVT treatment in the early time window for good outcome after ischemic stroke is cost-effective irrespective of the quality of collateral circulation, and patients should not be excluded from thrombectomy solely on the basis of collateral status. Despite relatively lower benefits of EVT in patients with poor collaterals, even smaller differences in better outcomes have significant long-term financial implications that make EVT cost-effective.

Cerebral ischemia and reperfusion initiate cellular events in brain that lead to neurological disability. Investigating these cellular events provides ample targets for developing new treatments. Despite considerable work, no such therapy has translated into successful stroke treatment. Among other issues—such as incomplete mechanistic knowledge and faulty clinical trial design—a key contributor to prior translational failures may be insufficient scientific rigor during preclinical assessment: nonblinded outcome assessment; missing randomization; inappropriate sample sizes; and preclinical assessments in young male animals that ignore relevant biological variables, such as age, sex, and relevant comorbid diseases. Promising results are rarely replicated in multiple laboratories. We sought to address some of these issues with rigorous assessment of candidate treatments across 6 independent research laboratories. The Stroke Preclinical Assessment Network (SPAN) implements state-of-the-art experimental design to test the hypothesis that rigorous preclinical assessment can successfully reduce or eliminate common sources of bias in choosing treatments for evaluation in clinical studies. SPAN is a randomized, placebo-controlled, blinded, multilaboratory trial using a multi-arm multi-stage protocol to select one or more putative stroke treatments with an implied high likelihood of success in human clinical stroke trials. The first stage of SPAN implemented procedural standardization and experimental rigor. All participating research laboratories performed middle cerebral artery occlusion surgery adhering to a common protocol and rapidly enrolled 913 mice in the first of 4 planned stages with excellent protocol adherence, remarkable data completion and low rates of subject loss. SPAN stage 1 successfully implemented treatment masking, randomization, prerandomization inclusion/exclusion criteria, and blinded assessment to exclude bias. Our data suggest that a large, multilaboratory, preclinical assessment effort to reduce known sources of bias is feasible and practical. Subsequent SPAN stages will evaluate candidate treatments for potential success in future stroke clinical trials using aged animals and animals with comorbid conditions.

Background: Social determinants of health are emerging as a key group of risk factors for cerebrovascular disease. Carotid artery stenosis (CAS) is an important risk factor for ischemic stroke. We hypothesize that community deprivation, an exposure that captures several social determinants for health, leads to significant disparities in healthcare access in patients with known CAS. Methods: We conducted a cross-sectional study within the All of Us Research Program, a prospective population study that aims to enroll 1 million Americans. We included study participants with CAS, as defined by validated ICD-9/10 codes. We evaluated access to healthcare using 5 metrics included in the Health Care Access and Utilization Survey (Table 1). We evaluated community deprivation using the Deprivation Index, a novel compound metric developed by the American Community Survey. We tested for association between tertiles of the Deprivation Index (labeled low, intermediate and high community deprivation) and health care access using multivariable models adjusting for potential confounders. Results: Of 333,845 participants enrolled in All of Us, we identified 2,465 (0.74%) participants with CAS (mean age 69, 53% female). Of these, 259 (10.5%) could not afford prescription medication, 132 (5.4%) could not afford specialist care, 144 (5.8) skipped medications, 109 (4.4%) could not afford follow up care and 97 (3.9%) could not afford mental health care. In unadjusted analysis, higher community deprivation was associated with a higher prevalence of all 5 evaluated indicators of poor access to health. In multivariable analysis adjusted for potential confounder variables, difficulty affording prescription medication, specialist care and follow up care remained statistically significant (Table 1). Conclusion: Among persons with CAS enrolled in All of Us, community deprivation was associated with a lower likelihood of accessing and utilizing important healthcare services.

Background: Optimal level blood pressure (BP) targets in acute stroke remain elusive. Tailored hemodynamic management after endovascular thrombectomy (EVT) may reduce the risk of reperfusion injury and promote penumbral recovery. Our study aimed to evaluate the relationship between personalized autoregulation-based BP targets, secondary brain injury, and functional outcomes. Methods: We prospectively enrolled 200 patients with acute ischemic stroke who underwent EVT. Autoregulatory function was continuously measured for >=24 hours using simultaneous recordings of near-infrared spectroscopy and mean arterial pressure (MAP). The resulting autoregulatory index was used to calculate and trend the BP range at which autoregulation was most preserved. Percent time and “dose” that MAP exceeded the upper limit or dropped below the lower limit of autoregulation (ULA, LLA) were calculated for each patient. Hemodynamic parameters were correlated with short-term clinical endpoints (symptomatic ICH), biomarkers of secondary brain injury (net water uptake, hemorrhagic transformation (HT), infarct progression), and 90-day functional outcomes. Results: Personalized BP targets were successfully computed in 195 patients (mean age 70 ± 16, 45% female, mean NIHSS 14, mean monitoring time 31 ± 28 hours). Time above the ULA was associated with worse functional outcomes at 90-days after adjusting for age, sex, NIHSS, ASPECTS and TICI (adjusted OR per 10% increase 1.4, 95% CI 1.1-1.6, P=0.004). The burden of hyperperfusion was significantly greater among patients with HT (median 2.7 vs. 3.2 mmHg*min, p=0.01) and sICH (median 2.8 vs. 4.8 mmHg*min, p=0.05) than in those without it. Furthermore, time spent above the ULA was significantly correlated with net water uptake at 72 hours (r=0.37, p=0.03). Among patients with unsuccessful reperfusion, there was a non-significant correlation between time below the LLA and infarct progression (r=0.35, p=0.064). Conclusions: In the largest study conducted to date, deviations from personalized BP targets were associated with an increased risk of secondary brain injury and worse functional outcomes. Autoregulation-oriented BP management represents a promising strategy for maximizing recovery after ischemic stroke.

Background: Patients with brain arteriovenous malformation (AVM) are at risk of intracranial hemorrhage (ICH). The epsilon 2 and 4 alleles within the APOE gene are well-described genetic risk factors for spontaneous, non-traumatic intraparenchymal hemorrhages. We tested the hypothesis that the APOE epsilon variants lead to higher risk of ICH in patients with AVMs. Methods: We conducted a two-stage (discovery and replication) genetic association study using individual-level data from the UK Biobank and the All of Us Research Program. We ascertained AVMs and ICH using validated ICD-9/10 codes. Genome-wide array genotyping was completed using the UK Biobank Axiom Array in the UK Biobank, and Illumina’s Global Diversity Array in All of Us. We used genotypic data on the APOE variants rs429358 and rs7412 to ascertain the epsilon 2 and 4 status. Within each study, we tested for association between APOE epsilon variants and ICH risk using multivariable logistic regression. Results: The discovery phase included 189 UK Biobank participants with an AVM (mean age 57 years, female sex 49%), including 37 (19.6%) that sustained an ICH. After adjusting by age, sex, and race/ethnicity, APOE epsilon 4 was associated with a higher risk of ICH (OR 4.20; 95%CI 1.99-9.25; p0.05). These results were replicated in 228 participants with AVMs enrolled in All of Us (mean age 56 years, female sex 66%), including 31 (13.6%) who sustained an ICH, where APOE epsilon 4 was associated with a higher risk of ICH (OR 2.73; 95%CI 1.05-7.22; p=0.038) whereas epsilon 2 was not (p>0.05). Conclusion: Among study participants with AVMs enrolled in two large population studies, the APOE epsilon 4 variants were associated higher risk of sustaining a brain bleed. These results point to shared pathophysiology with spontaneous intraparenchymal hemorrhages and provide support for further research focused on evaluating the role of APOE in risk stratification strategies.

Background: Patients with ischemic stroke have worse outcome if there is concomitant coronavirus 2019 (COVID-19) infection. We hypothesize that patients with intracerebral hemorrhage (ICH) during the pandemic era had worse outcomes than ICH patients during the pre-pandemic period, and that concomitant COVID-19 in ICH patients is associated with worse outcome. Methods: We analyzed data from Get With The Guidelines® Stroke. We implemented a two-stage design: first, we compared outcomes for ICH patients pre-pandemic (admitted between March 2019 and February 2020) with outcomes for ICH patients admitted during the pandemic (from March 2020 to February 2021); second, we compared outcomes of ICH patients with and without COVID-19 infection admitted during the pandemic (from March 2020 to February 2021). We used multivariable logistic regression adjusted by age, sex, race/ethnicity, and clinical covariates for in-hospital mortality and poor functional outcome using the modified Rankin Scale (mRS) at discharge (mRS >= 4) and a for length of stay (LOS). Results: The first stage included 62,743 pre-pandemic and 64,681 intra-pandemic ICH cases 64,681. ICH patients during the pandemic had worse outcomes, including higher modified rankin scale (mRS) (OR 1.10, CI 1.06-1.14) and higher mortality (OR 1.04, CI 1.01-1.07). The second stage included 60,091 COVID-19-negative and 1,326 COVID-19-positive ICH patients. Patients with concomitant COVID-19 infection had worse outcomes, including higher LOS (RR 1.32, CI 1.25-1.39), high mRS (OR 1.68, CI 1.40-2.01), and increased mortality (OR 1.50, CI 1.33-1.71). (Table). Conclusion: When comparing pre- and intra-pandemic cases of ICH, critically ill stroke patients admitted during the pandemic had worse outcomes. When comparing COVID-19 positive and negative ICH cases that happened during the pandemic, those with the infection had worse clinical outcomes. COVID-19 infection is an independent risk factor for poor outcomes in ICH.

Introductions: Clinical trials have shown that aspiration thrombectomy is as safe and effective as stent-retriever thrombectomy. Multiple improvements have been made to the aspiration technique over the last few years. In this study, we aim to assess the effect of aspiration catheter bore size on the outcomes of A direct aspiration first pass technique (ADAPT) thrombectomy. Methods: We included patients who underwent ADAPT thrombectomy for M1 or internal carotid artery terminus (ICA-T) occlusions in the Stroke Thrombectomy and Aneurysm (STAR) database. Patients included between July 2016 and July 2022. We compared baseline characteristics, procedural metrics and outcomes between patients who underwent thrombectomy using small bore (0.035”-0.060”), medium bore (0.062”-0.068”) and large bore (0.070”-0.074”) catheters. Results: A total of 1158 patients were included; 576 (49.7%) females, 645 (70%) White, and 464 (40.6%) received IV-tPA. No difference was noticed in age, sex, and vascular risk factors between the 3 different groups. There was higher rate of IV-tPA in the small-bore catheter group (48.8%) compared to the medium and large bore catheter groups (38.4% and 36.7%, respectively) (P=0.03). Procedure duration was shorter when using medium (20 min) and large (18 min) compared to small bore catheters (30 min) (P=0.01). Both medium and large bore catheters were associated with higher rate of successful recanalization (88.9% and 87.9%, respectively) compared to small bore catheters (81.6%) (P=0.010). However, the difference in successful recanalization or procedure duration between medium and large bore catheters was not significant. No difference was noted in the rate of symptomatic hemorrhagic transformation (sICH) (4.7%, 5.3%, and 7.1%; P=0.345), 90-day favorable outcome (modified Rankin Scale 0-2) (41.8%, 39.3%, 40.8%; P=0.766) or 90-day mortality (18.1%, 23.5%, 24.4%; P=0.111) between the groups. Conclusions: Higher rate of successful recanalization and shorter procedure duration were observed when using medium and large bore aspiration catheters compared with small bore catheters in ADAPT technique. However, these procedural benefits were not observed when comparing large bore to medium bore catheters.

Background: Mechanical thrombectomy (MT) has significantly improved clinical outcomes in acute ischemic stroke. We used single-cell RNA sequencing (scRNA-seq) to describe the landscape of human clots at single cell resolution seeking to provide greater mechanistic insight into stroke pathophysiology and to uncover an association with stroke origin. Methods: scRNA-seq was performed on 14 clots retrieved from 14 patients undergoing MT between October 2020-July 2022. We followed standard molecular biology and bioinformatics workflows for sample processing and data to characterize differences in cellular composition between clots of different stroke origin (atrial fibrillation (AF) and carotid atherosclerosis (CA)). Results: Clots revealed a significant heterogeneity of immune cells with major constituents including cells of the mononuclear phagocyte system (MPS) and neutrophils. The cellular populations most enriched in CA clots were B-cells and CD4+ T-cells. The cellular population most enriched in AF clots was red blood cells. When looking at cellular subpopulations of the MPS component, we found that CD16+ monocytes (intermediate and non-classical) were significantly more abundant than CD14+CD16- (classical) monocytes in all clots. Moreover, the proportions of CD16+ monocytes varied with stroke origin: the proportion of non-classical (CD14-CD16+) monocytes was higher in CA clots (p=0.05) whereas the proportion of intermediate monocytes (CD14+CD16+) was higher in FA clots (p=0.03). AF clots had upregulated biomarkers and pathways involved with AF or contractile dysfunction (IFI30, FABP4, PPAR, HOTAIR, ILK, Integrin). CA clots had upregulated biomarkers and pathways associated with cardiovascular diseases and atherogenesis (RNSE1, POLR2J3.1, PLTP, Sirtuin, FAK). (Figure) Conclusions: These results reveal a significant heterogeneity of immune cells and point to important differences in cellular composition associated with stroke etiology.

Background: Cerebral near-infrared spectroscopy (NIRS) is a useful tool to monitor real-time cerebral oxygenation levels. However, the mechanisms through which varying oxygenation levels during endovascular thrombectomy (EVT) affect functional outcomes remain to be determined. In this study, we categorized NIRS trends into descriptive “fingerprints” and examined the relationship between these fingerprints and neurological worsening. Methods: We enrolled patients that presented to Yale New Haven Hospital with large vessel occlusion acute ischemic stroke and underwent EVT. NIRS was implemented into the standard operating procedure. Time stamps of defined events (medication administration, recanalization, etc.) were synchronized with corresponding NIRS values. We inspected NIRS curves from arrival to angio-suite to time of recanalization. Neurological deterioration was defined as an increase of 4 points or more on the National Institutes of Health Stroke Scale (NIHSS). Results: Forty-eight patients (mean age 72 ± 13, mean NIHSS 14) were analyzed. Five “fingerprints” were observed in the affected hemisphere: sustained decreases, downward rSO2 peaks, no change, upward rSO2 peaks, and sustained increases (Fig. 1), which were assigned nominal values of -2, -1, 0, 1, and 2, respectively. After adjusting for age and admission NIHSS, sustained decreases and downward rSO2 peaks were independently associated with neurological deterioration (P = 0.0076, Fig. 2). Conclusions: Identifiable NIRS “fingerprints” of downward rSO2 peaks and sustained decreases in the affected hemisphere during EVT are associated with neurological deterioration. Further distillation of identifiable intraprocedural NIRS trends in real time could provide guidance for anesthesia and hemodynamic management during EVT to optimize patient outcomes after stroke.

Introduction: Management of anterior circulation emergent large vessel occlusion with tandem carotid occlusion (TCO) remains a challenge during mechanical thrombectomy (MT). To day, there is no consensus regarding emergent carotid stenting (ECS) in the setting of MT with TCO. We aimed to compare the outcomes of ECS versus conservative management (MT alone) among patients with TCO. Methods: Data from the Stroke Thrombectomy and Aneurysm Registry between 2010 and 2022 was interrogated. Only patients with concomitant occlusions of cervical carotid and proximal ipsilateral intracranial segments of the ICA or MCA were included in the analyses. We compared baseline, procedural charecteristics, successful reperfusion (mTICI 2b-3), favorable 90-day good outcomes (mRS 0-2), intravenous tPA administration and symptomatic ICH between patients who did or did not undergo ECS. Multivariate regression was performed adjusting for variables of clinical importance. Propensity score matching for IV tPA use was performed to explore its safety with stenting. Results: Among 9812 thrombectomy patients, 688 patients had TCO; 132 underwent emergent stenting and 444 had MT alone. Patients who did not undergo ECS had a higher prevalence of atrial fibrillation (33.9% Vs 9.2%, P Conclusion: ECS during MT for TCO appears to be safe and is associated with better clinical and angiographic outcomes compared to conservative management.

Background: While mechanical thrombectomy (MT) has become the standard of care for acute stroke patients presenting with large vessel occlusion (LVO) and salvageable brain tissue, limited data is currently available regarding the benefits of MT in patents with medium vessel occlusions (MeVO) especially in the posterior circulation (P2 occlusions). Methods: We used the Stroke Thrombectomy and Aneurysm registry (STAR) which included data from 35 stroke centers in North America, Europe, Asia, and South America. We included patients who presented with MeVO in the M2, M3 or P2 segments and underwent MT. We used a Generalized Linear Model to assess the relationship between location of occlusion and outcomes. Results: 9812 patients were included in STAR at the time of this analysis; 43 underwent MT for P2 occlusion, 130 underwent MT for M3 occlusion; and 1273 underwent MT for M2 occlusion. There was no difference in age, sex, race, rate of IV-tPA and stroke severity between patients in all 3 groups (Table 1). There was a trend toward lower rate of atrial fibrillation in patients with P2 and M3 occlusions. Patients with P2 occlusions were less likely to achieve successful recanalization (modified treatment in cerebral infarction score≥2b); intraarterial thrombolysis was used less in P2 occlusions (4.7% compared to 16.2% in M3 occlusions and 10.1% in M2 occlusions). However, there was no difference in the rate of successful first pass. On multivariable analysis, P2 occlusions were not associated with hemorrhagic transformation (OR 2.0, 95% CI 0.7-5.7, P 0.186), 90-day mortality (OR 0.5, 95% CI 0.2-1.4, P 0.183), or 90-day favorable outcome (OR 2.0, 95% CI 0.9-4.4, P 0.084). Conclusions: In this multicenter study, there was no significant difference in safety and efficacy of MT in patients with MeVOs in posterior circulation (P2 occlusions) compared to M2 and M3 occlusions. Improved techniques for successful recanalization are needed for posterior circulation MeVOs.

Background: Mechanical thrombectomy is standard of care for acute ischemic stroke secondary to LVO however MT failure (MTF) occurs in approximately 15% of cases. Objective: Investigate patient and procedural characteristics that predict MTF. Methods: Retrospective review of prospectively collected, Stroke Thrombectomy and Aneurysm Registry. Patients who underwent MT for LVO were included and categorized by MT Success (MTS) or MTF, defined as mTICI≥2b or Results: A total of 8452 patients were analyzed, and 1301(15.4%) experienced MTF.MTF patients were older(73 vs.71, p=0.008)had higher poor premorbid mRS(10.8% vs 8.4%, p=0.17).Onset to puncture was greater in MTF group(442 vs.411 min, p=0.006).There were more ICA occlusions(15.6% vs. 13.5%)and basilar occlusions(7.8% vs.6.2%)in the MTF group and more M1 occlusions(42.2%vs.37.5%)in the MTS group (p Conclusion: MTF is associated with more complications and worse outcome. Final use of aspiration and rescue intracranial stenting may increase chances of recanalization.

Background: Social determinants of health are emerging as a key group of risk factors for cerebrovascular disease. Carotid artery stenosis (CAS) is an important risk factor for ischemic stroke. We hypothesize that community deprivation, an exposure that captures several social determinants for health, leads to significant disparities in healthcare access in patients with known CAS. Methods: We conducted a cross-sectional study within the All of Us Research Program, a prospective population study that aims to enroll 1 million Americans. We included study participants with CAS, as defined by validated ICD-9/10 codes. We evaluated access to healthcare using 5 metrics included in the Health Care Access and Utilization Survey (Table 1). We evaluated community deprivation using the Deprivation Index, a novel compound metric developed by the American Community Survey. We tested for association between tertiles of the Deprivation Index (labeled low, intermediate and high community deprivation) and health care access using multivariable models adjusting for potential confounders. Results: Of 333,845 participants enrolled in All of Us, we identified 2,465 (0.74%) participants with CAS (mean age 69, 53% female). Of these, 259 (10.5%) could not afford prescription medication, 132 (5.4%) could not afford specialist care, 144 (5.8) skipped medications, 109 (4.4%) could not afford to follow up care and 97 (3.9%) could not afford mental health care. In unadjusted analysis, higher community deprivation was associated with a higher prevalence of all 5 evaluated indicators of poor access to health. In multivariable analysis adjusted for potential confounder variables, difficulty affording prescription medication, specialist care and follow up care remained statistically significant (Table 1). Conclusion: Among persons with CAS enrolled in All of Us, community deprivation was associated with a lower likelihood of accessing and utilizing important healthcare services.

Introduction: Conventional MRI (cMRI) is not routinely available post-mechanical thrombectomy (MT), which can preclude accurate infarction assessment. Our objective was to evaluate the use of low-field portable MRI (pMRI) for bedside evaluation post-MT, including its use as a post-procedural baseline monitor. Methods: Low-field pMRI was used to obtain bedside imaging in post-MT patients between December 2021 to August 2022 at Yale-New Haven Hospital. All pMRI exams were conducted in the standard ferromagnetic environment of the IR suite. Volumetric analyses were performed by a neuroradiologist using 3D Slicer software. If cMRI was not available for comparison, a CT was used. Patients’ charts were reviewed for pre-revascularization MAP and occurrences of MAP dropping by 10% and 20% from individual baselines between the time of pMRI and delayed imaging. Results: A total of 25 patients (64% females, median age 77 years-old [IQR 69.5-84.5]) underwent bedside pMRIs in the IR suite post-MT. The median time from last known normal to access was 6 hours [IQR 4-17]. The median pMRI examination time was 30 minutes [IQR 17-32]. Of the 24 patients with available delayed imaging, 7 (29.2%) had infarct progression compared to immediate post-MT pMRI, while 15 patients (62.5%) had stable/decreased stroke volume. Two patients (8.3%) had parenchymal hemorrhage type 2 and were excluded from further analysis. There was no statistically significant difference between the proportions of favorable TICI scores (85.7% in the infarct progression group vs. 92.3% in the stable/decreased infarct group, p=1.00). Patients with infarct progression had comparable pre-revascularization MAP compared to those with stable/decreased delayed infarct volume (mean of 100.3±4.6 vs. 101.9±15.9 respectively, p=0.727) but had more occurrences of MAP dropping by 10% and 20% of their baseline between the time of pMRI and delayed imaging (mean of 35.0±23.3 vs. 14.7±11.3 occurrences, p=0.011; and mean of 21.7±16.5 vs. 8.5±9.5 occurrences, p=0.026, respectively). Conclusions: The use of low-field MRI in the post-MT setting can facilitate benchmark brain monitoring and serial examinations to evaluate the impact of potential physiological perturbations that may impact ongoing brain injury.

We present a case of a pregnant patient with an unrepaired vein of Galen malformation (VGAM) and left ventricular (LV) dilation. Patients with VGAM lesions typically present during childhood with cardiac failure or developmental delay prompting embolization. Therefore, it is highly unusual for an adult to present with an unrepaired lesion.1 It poses challenges for obstetric and anesthetic management during pregnancy and delivery to reduce the risk of heart failure, arrhythmia, and intracranial hemorrhage. Our patient safely delivered a term neonate by cesarean delivery with neuraxial analgesia at a Level IV Maternal Care Center.

BackgroundEndovascular thrombectomy (EVT) has become the mainstay treatment for large vessel occlusion, with favorable safety and efficacy profile. However, the safety and efficacy of EVT in concurrent multi-territory occlusions (MTVOs) remains unclear.ObjectiveTo investigate the prevalence, clinical and technical outcomes of concurrent EVT for MTVOs.MethodsData were included from the Stroke Thrombectomy and Aneurysm Registry (STAR) with 32 stroke centers for EVT performed to treat bilateral anterior or concurrent anterior and posterior circulation occlusions between 2017 and 2021. Patients with MTVO were identified, and propensity score matching was used to compare this group with patients with occlusion in a single arterial territory.ResultsOf a total of 7723 patients who underwent EVT for acute ischemic stroke, 54 (0.7%) underwent EVT for MTVOs (mean age 69±12.5; female 50%). 28% had bilateral and 72% had anterior and posterior circulations occlusions. The rate of successful recanalization (Thrombolysis in Cerebral Infarction 2b/3), complications, modified Rankin score at 90 days, and mortality was not significantly different between the matched cohorts. Multivariate analysis confirmed that MTVOs were not associated with poor functional outcome, symptomatic intracranial hemorrhage, or longer procedure time.ConclusionCompared with EVT for single vessel occlusions, EVT in appropriately selected patients with MTVOs has a similar efficacy and safety profile.

BackgroundThe safety and efficacy of bridging therapy with intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in patients with large core infarct has not been sufficiently studied. In this study, we compared the efficacy and safety outcomes between patients who received IVT+MT and those treated with MT alone.MethodsThis is a retrospective analysis of the Stroke Thrombectomy Aneurysm Registry (STAR). Patients with Alberta Stroke Program Early CT Score (ASPECTS) ≤5 treated with MT were included in this study. Patients were divided into two groups based on pre-treatment IVT (IVT, no IVT). Propensity score matched analysis were used to compare outcomes between groups.ResultsA total of 398 patients were included; 113 pairs were generated using propensity score matching analyses. Baseline characteristics were well balanced in the matched cohort. The rate of any intracerebral hemorrhage (ICH) was similar between groups in both the full cohort (41.4% vs 42.3%, P=0.85) and matched cohort (38.55% vs 42.1%, P=0.593). Similarly, the rate of significant ICH was similar between the groups (full cohort: 13.1% vs 16.9%, P=0.306; matched cohort: 15.6% vs 18.95, P=0.52). There was no difference in favorable outcome (90-day modified Rankin Scale 0–2) or successful reperfusion between groups. In an adjusted analysis, IVT was not associated with any of the outcomes.ConclusionPretreatment IVT was not associated with an increased risk of hemorrhage in patients with large core infarct treated with MT. Future studies are needed to assess the safety and efficacy of bridging therapy in patients with large core infarct.

BackgroundThe benefit of complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 3) over near-complete reperfusion (≥90%, mTICI 2c) remains unclear. The goal of this study is to compare clinical outcomes between mechanical thrombectomy (MT)-treated stroke patients with mTICI 2c versus 3.MethodsThis is a retrospective study from the Stroke Thrombectomy and Aneurysm Registry (STAR) comprising 33 centers. Adults with anterior circulation arterial vessel occlusion who underwent MT yielding mTICI 2c or mTICI 3 reperfusion were included. Patients were categorized based on reperfusion grade achieved. Primary outcome was modified Rankin Scale (mRS) 0–2 at 90 days. Secondary outcomes were mRS scores at discharge and 90 days, National Institutes of Health Stroke Scale score at discharge, procedure-related complications, and symptomatic intracerebral hemorrhage.ResultsThe unmatched mTICI 2c and mTICI 3 cohorts comprised 519 and 1923 patients, respectively. There was no difference in primary (42.4% vs 45.1%; p=0.264) or secondary outcomes between the unmatched cohorts. Reperfusion status (mTICI 2c vs 3) was also not predictive of the primary outcome in non-imputed and imputed multivariable models. The matched cohorts each comprised 191 patients. Primary (39.8% vs 47.6%; p=0.122) and secondary outcomes were also similar between the matched cohorts, except the 90-day mRS which was lower in the matched mTICI 3 cohort (p=0.049). There were increased odds of the primary outcome with mTICI 3 in patients with baseline mRS ≥2 (36% vs 7.7%; p=0.011; pinteraction=0.014) and a history of stroke (42.3% vs 15.4%; p=0.027; pinteraction=0.041).ConclusionsComplete and near-complete reperfusion after MT appear to confer comparable outcomes in patients with acute stroke.

BackgroundDolichoectatic vertebrobasilar fusiform aneurysms (DVBFAs) have poor natural history when left untreated and high morbimortality when treated with microsurgery. Flow diversion (FD) with dual-antiplatelet therapy (DAPT) is feasible but carries high risk of perforator occlusion and progression of brainstem compression. Elaborate antithrombotic strategies are needed to preserve perforator patency while vessel remodeling occurs. We compared triple therapy (TT (DAPT plus oral anticoagulation)) and DAPT alone in patients with DVBFAs treated with FD.MethodsRetrospective comparison of DAPT and TT in patients with DVBFAs treated with FD at eight US centers.ResultsThe groups (DAPT=13, TT=14) were similar in age, sex, clinical presentation, baseline disability, and aneurysm characteristics. Radial access use was significantly higher in the TT group (71.4% vs 15.3%; P=0.006). Median number of flow diverters and adjunctive coiling use were non-different between groups. Acute ischemic stroke rate during the oral anticoagulation period was lower in the TT group than the DAPT group (7.1% vs 30.8%; P=0.167). Modified Rankin Scale score decline was significantly lower in the TT group (7.1% vs 69.2%; P=0.001). Overall rates of hemorrhagic complications (TT, 28.6% vs DAPT, 7.7%; P=0.162) and complete occlusion (TT, 25% vs DAPT, 54.4%; P=0.213) were non-different between the groups. Rate of moderate-to-severe disability at last follow-up was significantly lower in the TT group (21.4% vs 76.9%; P=0.007).ConclusionsPatients with DVBFAs treated with FD in the TT group had fewer ischemic strokes, less symptom progression, and overall better outcomes at last follow-up than similar patients in the DAPT group.

Brain imaging is essential to the clinical management of patients with ischemic stroke. Timely and accessible neuroimaging, however, can be limited in clinical stroke pathways. Here, portable magnetic resonance imaging (pMRI) acquired at very low magnetic field strength (0.064 T) is used to obtain actionable bedside neuroimaging for 50 confirmed patients with ischemic stroke. Low-field pMRI detected infarcts in 45 (90%) patients across cortical, subcortical, and cerebellar structures. Lesions as small as 4 mm were captured. Infarcts appeared as hyperintense regions on T2-weighted, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences. Stroke volume measurements were consistent across pMRI sequences and between low-field pMRI and conventional high-field MRI studies. Low-field pMRI stroke volumes significantly correlated with stroke severity and functional outcome at discharge. These results validate the use of low-field pMRI to obtain clinically useful imaging of stroke, setting the stage for use in resource-limited environments.

BackgroundEndovascular thrombectomy (EVT) is the standard-of-care for proximal large vessel occlusion (LVO) stroke. Data on technical and clinical outcomes in distal vessel occlusions (DVOs) remain limited.MethodsThis was a retrospective study of patients undergoing EVT for stroke at 32 international centers. Patients were divided into LVOs (internal carotid artery/M1/vertebrobasilar), medium vessel occlusions (M2/A1/P1) and isolated DVOs (M3/M4/A2/A3/P2/P3) and categorized by thrombectomy technique. Primary outcome was a good functional outcome (modified Rankin Scale ≤2) at 90 days. Secondary outcomes included recanalization, procedure-time, thrombectomy attempts, hemorrhage, and mortality. Multivariate logistic regressions were used to evaluate the impact of technical variables. Propensity score matching was used to compare outcome in patients with DVO treated with aspiration versus stent retrieverResultsWe included 7477 patients including 213 DVOs. Distal location did not independently predict good functional outcome at 90 days compared with proximal (p=0.467). In distal occlusions, successful recanalization was an independent predictor of good outcome (adjusted odds ratio (aOR) 5.11, pConclusionsOutcomes following EVT for DVO are comparable to LVO with similar results between techniques. Techniques may exhibit different futility metrics; stent retriever thrombectomy was influenced by attempts whereas aspiration was more dependent on procedure time.

Background: Impairment of cerebral autoregulation after subarachnoid hemorrhage (SAH) makes patients vulnerable to changes in blood pressure (BP). While oral nimodipine is recommended for improving neurological outcomes, its administration is frequently associated with reductions in BP. In this observational study, we examined the effect of nimodipine-induced BP reductions below personalized limits of autoregulation on outcome after aneurysmal SAH. Methods: Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure (MAP). The resulting autoregulatory index was used for trending the BP range at which autoregulation was most preserved. Cerebral hypoperfusion was defined as episodes with at least 30 minutes of MAP reductions below the lower limit of autoregulation (LLA) following nimodipine administration (Fig. 1). Functional outcome was measured with the modified Rankin Scale at 90 days. Results: We identified 593 occurrences of nimodipine administration with simultaneous recording of continuous physiologic data for 60 minutes before and after the intervention among 26 SAH patients (mean age 57 + 14, 21 F). Following nimodipine administration, the mean MAP decreased from 103 to 98 mmHg (p Conclusions: Nimodipine-induced BP reductions below the LLA may increase the risk of secondary brain injury and poor functional outcomes. A more personalized treatment approach accounting for cerebral autoregulation status could help identify vulnerable patients and maximize the benefit from current clinical interventions.

Introduction: Neutrophil-to-lymphocyte ratio (NLR) is a marker of acute inflammation after brain injury. We sought to evaluate the relationship between NLR at admission and 3-month outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods: We pooled individual level data from 2 prospective ICH cohorts, the Acute Brain Injury Biorepository at Yale and Brown ICH registry. We included patients with ICH who had available NLR at admission (exposure of interest) and 3-month modified Rankin Scale (mRS). The primary endpoint was poor outcome at 3-months, defined as mRS 4-6. In each cohort, we fit multivariable logistic regression models to test for association between NLR (natural log transformed and quartiles) and 3-month mRS. Multivariable models were adjusted for sex and components of the ICH score. We then pooled study-specific results using a random-effects (with inverse variance-weighting) meta-analysis. Results: 592 patients from Brown (69 years [SD 14], 47% female), and 107 patients from Yale (67 years [SD 14], 49% female) were included in the analysis. In the Brown cohort, average ICH volume was 9 cc and 64% of patients had lobar ICH. In the Yale cohort, ICH volume was 10.7 cc and 51% of patients had a lobar ICH. The NLR at admission was 8.21 [SD 9.39] in the Brown cohort and 6.98 [SD 11.35] in the Yale cohort (p=0.230). In the Brown cohort, NLR was associated with poor 3-month outcome in unadjusted (OR 1.28, 95% CI 1.06-1.54, p = 0.01) and adjusted analyses (OR 1.27, 95% CI 1.03-1.57, p = 0.03). In the Yale cohort, NLR yielded similar results in unadjusted (OR 1.80, 95% CI 1.11-2.92, p = 0.02) and adjusted analyses, although not statistically significant (OR 1.90, 95% 0.64-5.63, p = 0.24). Random effect models showed a consistent association in both unadjusted (OR 1.41; 95% CI, 1.04-1.90; p = 0.025; heterogeneity I 2 =40%; Q=1.67, p=0.2) and adjusted analyses (OR 1.29; 95% CI, 1.05-1.59; p=0.016; heterogeneity I 2 =68%; Q=0.49, p=0.48). Compared to the lowest quartile, the highest quartile of NLR had a 20% increase in the odds of having a poor outcome at 3 months (p=0.03). Conclusions: In a pooled study of two prospective cohorts, NLR was associated with poor functional outcome at 3 months. Future studies are needed to further evaluate NLR as a prognostic marker.

Introduction: The precise interactions between collateral perfusion, hemodynamics, and infarct growth after large vessel occlusion (LVO) require further definition. This study examined whether patients with poor collateral circulation and rapid early infarct progression are more vulnerable to reductions in blood pressure (BP). Methods: We prospectively enrolled patients with LVO stroke who underwent thrombectomy. Volumes of arterial tissue delay and relative cerebral blood flow (CBF) were estimated with RAPID software; a poor collateral profile was defined by a hypoperfusion intensity ratio >0.4. Early infarct growth rate (EIGR) was defined as ischemic core volume (CBF10 mL/h. The final infarct growth rate (FIGR) was the quotient of final infarct volume (FIV) and time from symptom onset to reperfusion. BP reduction was measured as the difference between admission mean arterial pressure (MAP) and lowest MAP before reperfusion. Results: Fifty-five patients (mean age 69 + 15, mean NIHSS 13) with successful reperfusion (TICI 2B/3) were included in the analysis. The median MAP reduction was 17 (IQR 9, 32). Poor collateral perfusion and EIGR were independent predictors of FIV after adjusting for age and admission NIHSS (mean FIV 70 vs. 31 mL, p=0.012 and 60 vs. 29 mL, p=0.01, respectively). A significant interaction was found between MAP reduction and both collateral status (p=0.04) and progressor profile (p=0.01). For every 10 mmHg MAP reduction, patients with poor collaterals experienced an average increase in FIGR of 3.6 mL/h (Fig. 1A). Above a critical MAP reduction threshold of 30 mmHg, mean FIV was significantly larger in patients with rapidly progressing infarcts (p Conclusions: Patients with poor collaterals and rapid early infarct growth are at higher risk of accelerated infarct growth and larger FIV related to BP reductions.

Introduction: High blood pressure variability (BPV) after endovascular thrombectomy is associated with post-stroke complications and poor neurological outcomes. However, whether BPV is an epiphenomenon of the stroke itself or causally related to the outcome remains unknown. Objective: In this study we aimed to evaluate if a relationship exists between pre-and post-stroke BPV in patients with large vessel occlusions (LVO). Methods: From our prospective stroke registry, we identified patients who had an anterior circulation LVO, underwent EVT, and had at least three blood pressure measurements recorded in the electronic medical record in the six months prior to their stroke admission. All patients had repeated time-stamped blood pressure data recorded for the first 72 hours after thrombectomy. Using the standard deviation of systolic BP, we calculated BPV for each patient and separated patients into tertiles based on their post-EVT BPV. The relationship between pre-stroke BPV and post-EVT BPV was analyzed using an ordinal logistic regression and Spearman’s rank correlation analysis. Results: Two hundred fifty-two patients were included in our analysis (mean age 70±16.2 years, mean admission NIHSS 15±7, median pre-stroke BP measurements 14.5 (IQR 5.0-55.8)). Pre-stroke BPV gradually increased for patients with higher post-EVT BPV tertiles (tertile 1 = 13.2(±5.2) mmHg, tertile 2 = 15.0(±5.5) mmHg, tertile 3 = 16.7(±7.0) mmHg, p=0.001). A positive correlation was observed between pre-stroke BPV and post-EVT BPV (p Conclusion: High pre-stroke BPV is correlated with high post-EVT BPV. Although larger, prospective studies are needed to provide definitive evidence of this relationship, our work suggests that high post-EVT BPV may be related to an underlying biological phenomenon and not merely a consequence of the stroke itself. Individuals with high BPV may benefit from more intensive blood pressure management in the acute phase after EVT.

Objective: The objective of this study is to assess the impact that the type and duration of DAPT has on aneurysm occlusion rates and iatrogenic complications following endoluminal flow diversion with a single flow diverting stent. Methods: A retrospective review of a multicenter aneurysm database was performed from 2012 to 2020 to identify unruptured intracranial aneurysms treated with single device flow diversion and >12-month follow-up. Clinical and radiologic data were analyzed with aneurysm occlusion as a function of DAPT duration serving as a primary outcome measure. Results: A total of 205 patients underwent flow diversion with a single pipeline embolization device. During the study period, 12.7% of treated aneurysms remained non-occluded. There were no significant differences in aneurysm morphology or type of DAPT used between occluded and non-occluded groups. Non-occluded aneurysms received a longer mean duration of DAPT (9.4 vs 7.1 mo, p=0.016) with ANOVA demonstrating a significant effect of DAPT duration on the observed aneurysm occlusion rate (F(2, 202)=4.2, p=0.016). An exploratory analysis demonstrated the optimum DAPT discontinuation time to minimize aneurysm non-occlusion rates was 7.9 months (95% CI: 6-11 months). There was no significant difference in the rate of complications or delayed ischemic strokes observed between patients receiving short (6 mo) DAPT (7.9% vs 9.3%, p=0.76). Conclusions: Following endovascular flow-diversion, an abbreviated duration of DAPT lasting 6 months may be most appropriate before transitioning to low-dose aspirin monotherapy to promote timely aneurysm occlusion while minimizing delayed thromboembolic complications.

Background: While existing evidence points to differences in the prevalence of Carotid Artery Stenosis (CAS) across race/ethnic groups, these differences have not been fully studied in underrepresented populations defined by other factors. We leveraged the recently introduced NIH All of Us Research Program to test the hypothesis that CAS disproportionally affects underrepresented groups defined by factors other than race/ethnicity. Methods: We evaluated data from the All of Us Research Program. We conducted a cross-sectional analysis including study participants with available data from both baseline questionnaires and electronic health records. We ascertained CAS using validated ICD-9/10 codes and corresponding Observational Medical Outcomes Partnership codes. Following the conceptual framework provided by All of Us, we considered underrepresented groups defined not only by race/ethnicity but also by gender identity/sexual orientation, education and income. We fitted multivariable logistic regression models adjusting for vascular risk factors. Results: We included 203,813 study participants in the analysis (mean age 51.5 (SD 16.7), 124,735 (61%) were female). The prevalence of CAS in the overall cohort was 2.7% (n=5,420). For underrepresented groups defined by factors other than race/ethnicity, income Conclusions: Among participants enrolled in the All of Us Research Program, lower income was associated with higher risk of CAS whereas Hispanic and Black race/ethnicity were associated with lower risk of CAS. These results underscore the importance of evaluating underrepresented groups beyond those defined by race/ethnicity and highlight the potential of the NIH All of Us Research Program to accelerate health disparities research on this topic.

Introduction: Secondary inflammation is a well-established cause of injury in intracerebral hemorrhage (ICH). One potential treatment for ICH limits inflammation through targeted metabolic modulation of immune cells, but leukocyte activation states in ICH are poorly defined. Using single-cell RNA sequencing (scRNA-seq) of patient hematoma evacuates, we characterized the inflammatory and metabolic profile of over a dozen identifiable leukocyte populations. This research provides insight into the dynamics of immune activation in ICH. Methods: Evacuated hematoma and peripheral blood samples from 8 ICH patients (62 ± 2.1 years) were collected via minimally invasive surgery (n=5) or craniotomy (n=3) (Fig. 1a). Collection time ranged from 0 to 4 days after ICH onset (1.5 ± 0.5 days). scRNA-seq was done on the 10X Genomics platform and analyzed using Seurat. Human monocyte-derived macrophage cultures were stimulated with S100A9 and IL-1β, two ICH-relevant inflammatory molecules, or LPS. Echinomycin and 2-deoxy-D-glucose were used to inhibit HIF signaling and glycolysis respectively. Results: Clustering revealed over a dozen transcriptionally distinct CNS-resident and immune cell types, many of which have little prior study in ICH (Fig. 1b). 3,395 differentially expressed genes between hematoma and peripheral blood (p+ monocytes and 932 in CD4 + effector T cells. Pathway analysis found upregulation of HIF signaling, glycolysis, and correlated networks of cytokine expression in the hematoma. The findings were significant across all immune populations but most prominent in myeloid cells (Fig. 1c). Inhibition of HIF and glycolysis in human macrophages in-vitro abrogated inflammatory and reparative cytokine production following inflammatory stimulation. In conclusion, this work highlights the interplay of inflammation and metabolism at a single cell level in ICH, contributing to knowledge of the immune response to brain injury.

BackgroundReducing intracranial hemorrhage (ICH) can improve patient outcome in acute ischemic stroke (AIS) intervention. We sought to identify ICH risk factors after AIS thrombectomy.MethodsThis is a retrospective review of the Stroke Thrombectomy and Aneurysm Registry (STAR) database. All patients who underwent AIS thrombectomy with available ICH data were included. Multivariable regression models were developed to identify predictors of ICH after thrombectomy. Subgroup analyses were performed stratified by symptom status and European Cooperative Acute Stroke Study (ECASS) grade.ResultsThe study cohort comprised 6860 patients. Any ICH and symptomatic ICH (sICH) occurred in 25% and 7% of patients, respectively. Hemorrhagic infarction 1 (HI1) occurred in 36%, HI2 in 24%, parenchymal hemorrhage 1 (PH1) in 22%, and PH2 in 17% of patients classified by ECASS grade. Intraprocedural complications independently predicted any ICH (OR 3.8083, PConclusionsThis study identified ICH risk factors after AIS thrombectomy using real-world data. There was a propensity towards a reduced sICH risk with direct aspiration. Procedural complications and ethnicity were predictors congruent between categories of any ICH, sICH, PH1, and PH2. Further investigation of technique and ethnicity effects on ICH and outcomes after AIS thrombectomy is warranted.

BackgroundRecent clinical trials have shown that mechanical thrombectomy is superior to medical management for large vessel occlusion for up to 24 hours from onset. Our objective is to examine the safety and efficacy of thrombectomy beyond the standard of care window.MethodsA retrospective review was undertaken of the multicenter Stroke Thrombectomy and Aneurysm Registry (STAR). We identified patients who underwent mechanical thrombectomy for large vessel occlusion beyond 24 hours. We selected a matched control group from patients who underwent thrombectomy in the 6–24-hour window. We used functional independence at 3 months as our primary outcome measure.ResultsWe identified 121 patients who underwent thrombectomy beyond 24 hours and 1824 in the 6–24-hour window. We selected a 2:1 matched group of patients with thrombectomy 6–24 hours as a comparison group. Patients undergoing thrombectomy beyond 24 hours were less likely to be independent at 90 days (18 (18.8%) vs 73 (34.9%), P=0.005). They had higher odds of mortality at 90 days in the adjusted analysis (OR 2.34, P=0.023). Symptomatic intracerebral hemorrhage and other complications were similar in the two groups. In a multivariate analysis only lower number of attempts was associated with good outcomes (OR 0.27, P=0.022).ConclusionsMechanical thrombectomy beyond 24 hours appears to be safe and tolerable with no more hemorrhages or complications compared with standard of care thrombectomy. Outcomes and mortality in this time window are worse compared with an earlier time window, but the rates of good outcomes may justify this therapy in selected patients.

AimTo use the Hospital Frailty Risk Score (HFRS) to investigate the impact of frailty on complication rates and healthcare resource utilization in patients who underwent endovascular treatment of ruptured intracranial aneurysms (IAs).MethodsA retrospective cohort study was performed using the 2016–2019 National Inpatient Sample database. All adult patients (≥18 years) undergoing endovascular treatment for IAs after subarachnoid hemorrhage were identified using ICD-10-CM codes. Patients were categorized into frailty cohorts: low (HFRS 15). Patient demographics, adverse events, length of stay (LOS), discharge disposition, and total cost of admission were assessed. Multivariate logistic regression analysis was used to identify independent predictors of prolonged LOS, increased cost, and non-routine discharge.ResultsOf the 33 840 patients identified, 7940 (23.5%) were found to be low, 20 075 (59.3%) intermediate and 5825 (17.2%) high frailty by HFRS criteria. The rate of encountering any adverse event was significantly greater in the higher frailty cohorts (low: 59.9%; intermediate: 92.4%; high: 99.2%, pConclusionsOur study found that greater frailty as defined by the HFRS was associated with increased complications, LOS, total costs, and non-routine discharge.

BackgroundTo evaluate the cost-effectiveness of endovascular thrombectomy (EVT) to treat large vessel occlusion (LVO) in patients with acute, minor stroke (National Institute of Health Stroke Scale (NIHSS) MethodsA Markov decision-analytic model was constructed accounting for both costs and outcomes from a societal perspective. Two different management strategies were evaluated: EVT and medical management. Base case analysis was done for three different sites of occlusion: proximal M1, distal M1 and M2 occlusions. One-way, two-way and probabilistic sensitivity analyses were performed.ResultsBase-case calculation showed EVT to be the dominant strategy in 65-year-old patients with proximal M1 occlusion and NIHSS ConclusionsEVT is cost-effective in patients with minor stroke and LVO in the long term (lifetime horizon), considering the poor outcomes and significant disability associated with non-reperfusion. Our study emphasizes the need for caution in interpreting previous observational studies which concluded similar results in EVT versus medical management in patients with minor stroke due to a high proportion of patients with M2 occlusions in the two strategies.

Background and Purpose: Epidemiological studies have shown racial and ethnic minorities to have higher stroke risk and worse outcomes than non-Hispanic Whites. In this cohort study, we analyzed the STAR (Stroke Thrombectomy and Aneurysm Registry) database, a multi-institutional database of patients who underwent mechanical thrombectomy for acute large vessel occlusion stroke to determine the relationship between mechanical thrombectomy outcomes and race. Methods: Patients who underwent mechanical thrombectomy between January 2017 and May 2020 were analyzed. Data included baseline characteristics, vascular risk factors, complications, and long-term outcomes. Functional outcomes were assessed with respect to Hispanic status delineated as non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic patients. Multivariate analysis was performed to identify variables associated with unfavorable outcome or modified Rankin Scale ≥3 at 90 days. Results: Records of 2115 patients from the registry were analyzed. Median age of Hispanic patients undergoing mechanical thrombectomy was 60 years (72–84), compared with 63 years (54–74) for NHB, and 71 years (60–80) for NHW patients ( P P P P Conclusions: Hispanic patients are less likely to have favorable outcome at 90 days following mechanical thrombectomy compared to NHW or NHB patients. Further prospective studies are required to validate our findings.

Key Points Question What is the 90-day outcome for patients with stroke presenting with an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 2 to 5 who underwent mechanical thrombectomy? Findings In this multicenter cohort study of 2345 patients presenting with an intracranial internal carotid artery or M1 occlusion who underwent mechanical thrombectomy, 213 [9.1%] had an ASPECTS of 2 to 5, and 22% of these patients achieved favorable 90-day outcomes (modified Rankin scale score of 0-2). Patients who achieved successful recanalization were nearly 5 times more likely to achieve favorable outcomes compared with patients who had unsuccessful recanalization. Meaning This study suggests that patients with a low ASPECTS on presentation may achieve 90-day functional independence after mechanical thrombectomy if they achieve successful recanalization., Importance Limited data are available about the outcomes of mechanical thrombectomy (MT) for real-world patients with stroke presenting with a large core infarct. Objective To investigate the safety and effectiveness of MT for patients with large vessel occlusion and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 2 to 5. Design, Setting, and Participants This retrospective cohort study used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combines the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia. The study included 2345 patients presenting with an occlusion in the internal carotid artery or M1 segment of the middle cerebral artery from January 1, 2016, to December 31, 2020. Patients were followed up for 90 days after intervention. The ASPECTS is a 10-point scoring system based on the extent of early ischemic changes on the baseline noncontrasted computed tomography scan, with a score of 10 indicating normal and a score of 0 indicating ischemic changes in all of the regions included in the score. Exposure All patients underwent MT in one of the included centers. Main Outcomes and Measures A multivariable regression model was used to assess factors associated with a favorable 90-day outcome (modified Rankin Scale score of 0-2), including interaction terms between an ASPECTS of 2 to 5 and receiving MT in the extended window (6-24 hours from symptom onset). Results A total of 2345 patients who underwent MT were included (1175 women [50.1%]; median age, 72 years [IQR, 60-80 years]; 2132 patients [90.9%] had an ASPECTS of ≥6, and 213 patients [9.1%] had an ASPECTS of 2-5). At 90 days, 47 of the 213 patients (22.1%) with an ASPECTS of 2 to 5 had a modified Rankin Scale score of 0 to 2 (25.6% [45 of 176] of patients who underwent successful recanalization [modified Thrombolysis in Cerebral Ischemia score ≥2B] vs 5.4% [2 of 37] of patients who underwent unsuccessful recanalization; P = .007). Having a low ASPECTS (odds ratio, 0.60; 95% CI, 0.38-0.85; P = .002) and presenting in the extended window (odds ratio, 0.69; 95% CI, 0.55-0.88; P = .001) were associated with worse 90-day outcome after controlling for potential confounders, without significant interaction between these 2 factors (P = .64). Conclusions and Relevance In this cohort study, more than 1 in 5 patients presenting with an ASPECTS of 2 to 5 achieved 90-day functional independence after MT. A favorable outcome was nearly 5 times more likely for patients with low ASPECTS who had successful recanalization. The association of a low ASPECTS with 90-day outcomes did not differ for patients presenting in the early vs extended MT window., This cohort study uses data from the Stroke Thrombectomy and Aneurysm Registry to investigate the safety and effectiveness of mechanical thrombectomy for patients with large vessel occlusion and an Alberta Stroke Program Early Computed Tomography Score of 2 to 5.

Approximately 10% of dementia patients have idiopathic normal pressure hydrocephalus (iNPH), an expansion of the cerebrospinal fluid (CSF)-filled brain ventricles. iNPH and Alzheimer's disease (AD) both exhibit sleep disturbances, build-up of brain metabolic wastes and amyloid-β (Aβ) plaques, perivascular reactive astrogliosis, and mislocalization of astrocyte aquaporin-4 (AQP4). The glia–lymphatic (glymphatic) system facilitates brain fluid clearance and waste removal during sleep via glia-supported perivascular channels. Human studies have implicated impaired glymphatic function in both AD and iNPH. Continued investigation into the role of glymphatic system biology in AD and iNPH models could lead to new strategies to improve brain health by restoring homeostatic brain metabolism and CSF dynamics.