bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP111: Intra-Arterial Administration of Cerebral Endothelial Cell Derived Small Extracellular Vesicles Reduces Neurovascular Damage and Improves Neurological Outcome After Acute Ischemia in the Aged Rat
Authors: Teng Hua , Zhang Li , Luo Hao , Chopp Michael , Zhang Zheng Gang
Published: February 2024

Stroke is a leading cause of death and disability worldwide, mainly affecting the elderly. Endovascular thrombectomy (EVT) is a standard of care therapy for stroke patients with large-vessel occlusion, however, the majority of these patients do not achieve full functional improvement. The present study tested the hypothesis that intra-arterial (IA) administration of cerebral endothelial cell derived small extracellular vesicles (CEC-sEVs) following transient middle cerebral artery occlusion (tMCAO) improves stroke outcome in the aged rat. CEC-sEVs (1x10
11
particles/injection) isolated from healthy adult rats were employed. Male aged rats (18 months, n=10/group) subjected to 3h tMCAO were randomly divided into the experimental groups. To examine whether IA injection of CEC-sEVs improves stroke outcome, CEC-sEVs were administered via the internal carotid artery (ICA) immediately following reperfusion by withdrawal of the occlusion filament. To examine whether intravenous administration (IV) of CEC-sEVs during tMCAO and then followed by IA CEC-sEVs upon reperfusion further enhances stroke outcome, CEC-sEVs were given at 30 min of tMCAO via a tail vein and upon reperfusion via the ICA. The ischemic rats treated with IA saline were used as a control. Neurological outcome and infarct volume were assessed in a blinded manner. IA CEC-sEVs upon reperfusion significantly reduced infarct volume (24±5% vs 31±6% in saline, p<0.05) which was associated with robust improvement of neurological function from weeks 2 to 4 after tMCAO compared to saline treated rats. Moreover, rats treated with CEC-sEVs IV at 30min followed by IA treatment upon reperfusion further reduced infarct volume (16±6%) compared to rats treated with IA saline or CEC-sEVs. These rats also exhibited robust and early improvement of neurological function starting at 1d after tMCAO. In conclusion, IA administration of CEC-sEVs upon reperfusion significantly reduces ischemic damage, while an additional early (30min post stroke) dose of IV CEC-sEVs further enhances and accelerates the therapeutic effect of IA CEC-sEVs in the aged rats after tMCAO. Our data suggest that CEC-sEVs could potentially may be a therapy to amplify the efficacy of EVT even for elderly patients with acute ischemic stroke.
Abstract WMP114: EZH2 Inhibitor Improves Cognitive Behavior in CAA
Authors: Iqbal Zahid , El Hamamy Ahmad , Le Ngoc Mai , Ranjan Arya , Qi Li , Tan Chunfeng , McCullough Louise D , Li Jun
Published: February 2024

Introduction:
Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-β (Aβ) in the leptomeningeal and cortical vessels. CAA may lead to dementia and stroke; however effective options currently are very limited to treat or halt CAA progression. EZH2 (enhancer of zeste 2 polycomb repressive complex 2) is a histone methyltransferase, a key regulator of inflammation and microglia phagocytosis. The present study investigates the therapeutic potential of an EZH2 inhibitor (GSK343) in CAA mice.

Methods:
Brain samples were collected from a cohort of 4 WT and 4 TgSwDI (CAA model) male mice and lysed for immunoblot analysis to quantify EZH2 and H3K27me3 expression levels. A second cohort of 10 WT and 20 TgSwDI male mice (15 months old) were randomly assigned into DMSO (vehicle) and GSK343 groups. After performing baseline behavioral testing (Barnes maze and NORT), WT and TgSwDI-DMSO groups were injected with 0.1% DMSO while TgSwDI-GSK343 groups were injected with GSK343 (5 mg/kg) every other day intraperitoneally. After 6 weeks of treatment, behavioral testing was performed, and brain tissues were collected for IHC. Data are presented as Mean±SEM.

Results:
Immunoblot assays showed elevated expression of EZH2 and H3K27me3 in TgSwDI in comparison to WT mice. TgSwDI mice injected with GSK343 had improvements in the ability to recognize a novel object (58.36%±1.84) as compared to TgSwDI controls (45.04%±3.41) in the NORT (
p
= 0.0006). The latency to escape (63.08±2.86) was significantly faster in GSK343-treated mice compared to TgSwDI control mice (77.34±3.43) in the Barnes maze (
p
= 0.003). IHC results were in line with behavioral testing as GSK343 reduced the expression of EZH2 and Aβ in the hippocampus and frontal cortex.

Conclusions:
Our study revealed that EZH2 expression is upregulated in the brain of CAA-model mice. Pharmacological inhibition of EZH2 improved cognitive outcomes in CAA mice, suggesting a possible therapeutic target.
Abstract WMP115: Rapid Vascular Complement Activation: A Key Driver of Blood-Brain Barrier Disruption in Ischemic Stroke With Acute Hyperglycemia
Authors: Chen Hansen , Chiang Terrance , Kopchock Richard , Kim Anika , Tomlinson Stephen , Bliss Tonya , Cheng Michelle Y , Steinberg Gary
Published: February 2024

Background:
Acute hyperglycemia, which occurs in over 40% of ischemic stroke patients irrespective of pre-existing diabetes, exacerbates stroke injury. Understanding its mechanisms is vital for innovative treatments. Here we investigate the role of complement in hyperglycemia-exacerbated damage after stroke.

Method:
Male C57/BL6 mice (10-11 weeks) underwent 30-min suture-induced middle cerebral artery occlusion followed by reperfusion, resembling clinical thrombectomy. Acute hyperglycemia was induced 10 min pre-stroke via glucose injection. Mice were sacrificed at 4.5h and 24h post-stroke to analyze brain swelling, blood-brain barrier (BBB) leakage and hemorrhagic transformation (HT). Mortality, neurological deficits, and motor-sensory functions were assessed at 14 days post-stroke. Complement activation was visualized via C3d immunostaining. Complement C3's role was examined using knock-out mice and the targeted complement inhibitor CR2-Crry fusion protein.

Result:
Hyperglycemia rapidly worsens BBB leakage (p<0.0001), brain swelling (p<0.05), and HT (p<0.0001) at 4.5 hr after stroke. Hyperglycemic stroke mice exhibit higher mortality (100% vs 25%, p=0.0008), body weight loss, and behavior impairment at the sub-acute phase compared to normoglycemic mice. Notably, acute hyperglycemia rapidly increased plasma C3 levels at 1hr after stroke (p<0.01), accompanied by rapid and time-dependent activation of C3 in ischemic brain vessels, as marked by increased vascular C3d; and this co-localized with autoantibody (IgM/IgG) vessel buildup and vessel leakage. Additionally, C3d levels positively correlated with brain swelling and HT (p<0.01). Vascular C3d and leakage into parenchyma were markedly reduced in the absence of reperfusion. Blocking complement via C3 knock-out or post-reperfusion systemic injection of C3 inhibitor CR2-Crry mitigates hyperglycemia's detrimental effects, including BBB leakage.

Conclusion:
Rapid vascular activation of complement C3 is a significant driver of hyperglycemic-exacerbated pathology in experimental stroke. Inhibiting C3 activation could be a potential therapeutic approach to improve hyperglycemic stroke outcome.
Abstract WMP117: Altered Patterns of microRNA 9-3p in Acute Ischemic Stroke With Large Vessel Occlusion
Authors: Rout Madhusmita , Vaughan April , Blair Apple , Stavrakis Stavros , Sidorov Evgeny V , Sanghera Dharambir K
Published: February 2024

Background:
Stroke is a significant health issue in the United States, and identifying biomarkers for preventing acute ischemic stroke (AIS) remains the highest priority. This study aims to identify microRNA (miRNA) associated with AIS pathophysiology through longitudinal and case-control studies.

Methods:
We examined global miRNA profiles of serum exosome vesicles of 15 patients with a large vessel occlusion (LVO) using NextGen sequencing. Discovery cohort consisted of miRNA profiles collected during acute (<72 hours, T1) and chronic (3-5 months, T2) stroke stages. The preliminary results were validated through Validation set-1 included 55 LVO cases and 53 controls. and Validation set-2 comprised 15 LVO patients collected at different time points <24h-A1, 48-72h-A2, 5-7 days-A3, >3 months-A4.

Results:
Our study identified four miRNAs, miR-9-3p, miR-129-5p, miR-223-3p, and miR-423-5p, with differential expressions in LVOs compared to controls. Exosomal miR-9-3p showed a 14.7-fold increase in T1 (Bonferroni p= 9.4x10
-6
) in the Discovery set and a 9.39-fold increase (Bonferroni p= 1.3x10
-4
) in stroke cases compared to controls in the Validation-set-1. In the longitudinal analysis of Validation set-2, miR-9-3p levels peaked significantly at A2 and then gradually decreased over A3 and A4 time points. Though miR-129-5p and miR-423-5p were also significantly upregulated during the T1, their association did not survive the stringent Bonferroni correction in any sets.

Discussion and Conclusion:
MiR-9-3p triggers brain injury via caspase pathway in the murine stroke model. Its role in human AIS pathophysiology is not available. For the first time, we report the possible contribution of miR-9-3p during the acute state in LVO strokes. The pathway analysis suggests miR-9-3p may lead to neuronal cell death and apoptosis in AIS. If confirmed, therapeutic targeting of miRNA 9-3p may become clinically useful biomarkers for treating LVO in humans.

Funding:
College of Medicine Alumni Association, the Presbyterian Health Foundation, Leinbach Foundation grants, and Dr. Geoffrey Altshuler Endowment funds from the Children’s Health Foundation of OUHSC, and partly supported by National Institute of Health (NIH/NIDDK) R01DK118427 grant.
Abstract WMP16: Multi-Marker Cerebral Small Vessel Disease Score and Risk of Incident Dementia in the Framingham Heart Study
Authors: Pinheiro Adlin , Demissie Serkalem , Ekenze Oluchi , Aparicio Hugo J , Gonzalez Mitzi , Pase Matthew P , Beiser Alexa , De Carli Charles , Seshadri Sudha , Romero Jose R
Published: February 2024

Background:
Individual magnetic resonance imaging (MRI) markers of cerebral small vessel disease (CSVD) are associated with impaired cognition and dementia but may not reflect the overall burden of CSVD. It is unclear whether these markers provide additional value in evaluating the risk of dementia beyond assessments based solely on clinical risk factors. Thus, we aimed to determine whether the association of additive burden of multiple CSVD markers was independent of vascular risk factors and the Framingham Stroke Risk Profile (FSRP) and to also compare results with the FSRP.

Methods:
We included 1,152 Framingham Heart Study (FHS) participants over the age of 55, free of stroke and dementia, from the Original and Offspring cohorts with available MRI and FSRP data. CSVD score was calculated by summing the number of CSVD features detected in the MRI: cerebral microbleeds, cerebral brain infarcts, extensive white matter hyperintensities, severe perivascular spaces, and cortical superficial siderosis. Two Cox proportional hazards regression models were used to relate the multi-marker CSVD score to incident all-cause dementia and Alzheimer’s dementia. The first model adjusted for education, cohort, and clinical risk factors while the second adjusted for education, cohort, and FSRP.

Results:
Mean age was 70.9 years (SD: 8.7), 527 (46%) were male, and 211 (18%) had score ≥ 2. Over a median follow-up time of 6.4 years (Q1-Q3: 4.6-11.3), participants with score ≥ 2 had elevated risk of all-cause dementia compared to those with no CSVD markers after adjustment for FSRP (HR: 2.32; 95% CI: 1.46-3.69; p<0.001) and vascular risk factors (HR: 1.76; 95% CI: 1.10-2.81; p=0.02). Score ≥ 2 was also significantly associated with AD after adjustment for FSRP (HR: 2.05; 95% CI: 1.19-3.62; p<0.01), but not vascular risk factors (HR: 1.50; 95% CI: 0.87-2.60; p=0.15). In addition, a 5-percent increase in FSRP was independently associated with incident dementia after adjustment for education and FHS cohort (HR: 1.21; 95% CI: 1.13-1.30; p<0.001).

Conclusions:
Our results support the use of CSVD score as an indicator for dementia risk and it may be as robust as the FSRP. Further studies are necessary to validate the use of CSVD score in quantifying dementia risk.
Abstract WMP24: Association of the Mediterranean Diet With White Matter Integrity Among Hispanics/Latinos. Results From the Study of Latinos-Investigation of Neurocognitive Aging-MRI Ancillary Study
Authors: Trifan Gabriela , Moustafa Bayan , Isasi Carmen R , Lipton Richard , Sotres-Alvarez Daniela , Cai Jianwen , Tarraf Wassim , Stickel Ariana , Mattei Josiemer , Talavera Gregory A , Maillard Pauline , Daviglus Martha L , Gonzalez Hector , De Carli Charles , Testai Fernando
Published: February 2024

Objective:
Investigate the association between adherence to the Mediterranean Diet (MeDi) and white matter (WM) integrity among Hispanic/Latino adults.

Background:
High adherence to a MeDi was associated with better cognitive performance and decreased memory decline among Hispanic or Latino adults.

Methods:
We included 2,342 participants from the Study of Latinos-Investigation of Neurocognitive Aging-MRI Ancillary Study. Participants completed 24-hour dietary recalls at baseline (2008-2011) which were used to calculate a MeDi score (MeDiS). Brain MRI and diffusion tensor images were collected between 2018 and 2022 on a 3T MRI scanner using a standardized protocol. WM integrity was ascertained using WM hyperintensity (WMH) volume, fractional anisotropy (FA), and peak skeletonized mean diffusivity (PSMD). WMH volumes were residualized for total cranial volume and Ln-transformed prior to analysis. The association of MRI outcomes with MeDiS was investigated using weighted linear regression analysis with complex survey design adjusting for age, sex, sociodemographic characteristics, and Framingham Risk Score.

Results:
Mean age (95% CI) at MRI scan was 64.03 (63.1 - 64.9) and 44% were males. Mean MeDiS was 5.05 (4.92 - 5.17). In our fully adjusted model, increasing MeDiS was associated with decreased LnWMH volume (β=-0.07, 95% CI -0.10 to -0.03) and PSMD (β=-0.004, 95% CI -0.006 to -0.002), and increasing FA (β=0.002, 95% CI 0.001 to 0.003). When participants were grouped by background, the results were retained for all the groups except for Puerto Ricans and Mexicans.

Conclusions:
Among diverse Hispanic/Latino adults, high MeDi adherence was associated with preserved WM integrity. Since our preliminary results were retained after adjustment for Framingham Risk Score, this suggests that vascular mechanisms do not fully account for the observed associations. In addition, our results highlight that the results obtained in selected cohorts may not be generalizable to other Hispanic/Latino heritages. A culturally tailored MeDi may preserve brain health among Hispanic/Latino adults.
Abstract WMP43: Disparities in Large Vessel Occlusion Stroke Imaging and Endovascular Treatment Metrics, and Procedural Exclusions in the Global Registry of Stroke Care Quality (Res-Q)
Authors: Asif Kaiz S , Sedani Rupal , Bornstein Natan M , Hill Michael D , Lavados Pablo M , Martins Sheila C , Middleton Sandy , Sohn Sung-il , Jankanicova Natalia , Suwanwela Nijasri , Sylaja PN , Nguyen Huy Thang , Tsivgoulis Georgios K , Van Der Worp H B , Ortega-Gutierrez Santiago , Yavagal Dileep R , Mikulik Robert
Published: February 2024

Introduction:
Global access to mechanical thrombectomy for large vessel occlusion (LVO) stroke is low and disparate between regions. Comparative global data on time metrics for imaging and endovascular treatment (EVT) performance, as well as the reasons for excluding EVT, are lacking.

Methods:
This is a cross-sectional study using quality metrics from the Res-Q registry on patients presenting directly to the hospital with acute ischemic stroke from January 1, 2022, to December 31, 2022, in countries with 200 or more cases. We used descriptive statistical methods to study the time metrics of interest including door to imaging and door to puncture. Additionally, reasons for not performing thrombectomy in patients with LVO were collected (Table 1).

Results:
Among the 153,181 patients from 912 hospitals across 67 countries enrolled in the Res-Q registry, 125,390 had an acute ischemic stroke. After excluding secondary transfers (n=26,648), patients with missing or erroneous data (n=42,232), and countries with less than 200 cases (n=1,626), data from a total of 54,884 patients from 631 hospitals across 30 countries were analyzed. CT angiography (CTA) was performed in 24,215 (44.1%) patients and EVT was done in 3,649 (6.6%) patients. For patients who had simultaneous CT+CTA, the median door-to-CTA time was 27.5 min (IQR 22.5-33.9) and the median door-to-puncture time was 98.5 (IQR 79.8-129.3) minutes. The most prevalent specific reason for excluding EVT in patients with LVO on CTA/MRA was the presentation in the late time window (42.0%). Only 11 (36.7%) countries achieved a median door-to-puncture time within 90 minutes (Table 1).

Conclusions:
The performance of acute imaging for LVO detection and time metrics for EVT appear to be disparate between countries and warrant further study. Additional data from global stroke care quality registries are needed to set benchmarks, compare regional stroke systems of care, and identify gaps to mobilize resources appropriately.
Abstract WMP47: Neighborhood Socio-Economic Status as a Predictor of All-Cause Long-Term Post-Stroke Mortality
Authors: Nobel Lisa , Robinson David , Stanton Robert J , Becker Christopher , Kleindorfer Dawn O , Alwell Kathleen , Ding Lili , Khatri Pooja , Adeoye Opeolu M , Ferioli Simona , Mackey Jason , Woo Daniel , Martini Sharyl , DeLosRiosLa Rosa Felipe , Demel Stacie , Madsen Tracy , Star Michael , Coleman Elisheva R , Walsh Kyle , Slavin Sabreena , Jasne Adam S , Mistry Eva , Haverbusch Mary , Kissela Brett M
Published: February 2024

Background:
Previous studies have shown that neighborhood socioeconomic status may be associated with post-stroke mortality. However, these studies did not adjust for stroke severity. We aim to determine the association between neighborhood of residence on long-term mortality after stroke.

Methods:
Within our population of 1.3 million in the Greater Cincinnati Northern Kentucky area, incident strokes among adult residents were ascertained at all area hospitals during calendar years 2005, 2010 and 2015. Participants addresses were used to geocode and determine their census tract and then used a validated index to determine neighborhood socio-economic status. We used national death index data to determine mortality status at 5 years post stroke. Individuals who survived at least 30 days were included in the analysis. We used cox proportional hazards to determine the association between neighborhood of residence deprivation and case fatality rate after stroke.

Results:
Among 4514 incident ischemic strokes, there were 1719 deaths over 5 years; for an all-cause post-stroke mortality rate of 38.08% among survivors of 30 days post-stroke. Similarly, there were 552 intracerebral hemorrhages with 224 deaths over 5 years: yielding an all-cause post-stroke mortality rate of 40.58%. Individuals in the quartile of neighborhoods with lowest neighborhood socio-economic status had 1.3 times the all-cause post-stroke mortality rate (HR 1.29 95% CI 1.08-1.54); after adjustment for age sex, race, and year of study (2005, 2010 and 2015). After adjustment for age, race, sex, year of study and NIH stroke scale score, individuals living in the quartile of neighborhoods with the lowest neighborhood socio-economic status had 1.29 times the risk of dying (HR 1.29 95% CI 1.09-1.53). We found insufficient evidence of an association between neighborhood socio-economic status and 5-year case fatality rate among intracerebral hemorrhages.

Conclusion:
Rates of all-cause post-stroke long-term mortality were higher among patients with ischemic stroke who lived in neighborhoods with lowest quartile of socio-economic status. This effect persisted even after adjusting for stroke severity.
Abstract WMP57: Systematic Reduction of Neurochecks Overnight Decreases Length of Stay and Post-Stroke Delirium
Authors: Palmer Charles , Jacks Kevin , Harvey Jillian , Smolenski Elizabeth , Woolbright Emma , Blake Christina E , Holmstedt Christine A , Kalivas Benjamin
Published: February 2024

Introduction:
Post-stroke delirium is common and leads to worse short- and long-term outcomes with higher 28-day modified Rankin Score (mRS), longer length of hospitalization, and increased odds of discharge to a nursing home, development of dementia, and death. Circadian rhythm disturbances have been implicated as a core mechanism in the pathogenesis of delirium as well as a common sequela of stroke. Standard of care for acute stroke patients is to receive q1h-q4h neuro checks overnight to ensure stability and these are typically continued throughout hospitalization; however, there is limited evidence to support extended use and frequent checks have been implicated in increased delirium rate. Our pilot study addresses this problem by proactively holding neuro checks overnight on clinically stable patients with the goal of promoting re-institution of circadian rhythm as a delirium prevention measure.

Methods:
After at least 24 hours of hospitalization, patients who were felt to be clinically stable had neuro checks discontinued overnight between the hours of 8pm and 4am and efforts were made to bundle care around these times. If patients were felt not to be stable enough to reduce neuro checks, neuro checks were continued at the frequency typical of the usual standard of care. Patients were reassessed daily to determine if they were stable for neuro check decrease. The Confusion Assessment Method (CAM) was performed each shift with a positive result indicative of delirium.

Results:
290 patients over 12 months were included in the analysis (157 pre-intervention, 133 post-intervention). Demographic data did not differ significantly between groups. After the intervention was initiated, CAM positivity decreased from 34% to 23% (p=0.017). LOS decreased from 6.6 days to 5.1 days (p=0.024). mRS and NIHSS during hospitalization did not significantly change (NIHSS p=0.97, mRS p=0.38).

Conclusions:
After the introduction of the intervention, delirium rate and length of stay decreased significantly. In conclusion, holding neuro checks overnight for clinically stable patients may decrease delirium rate and length of stay, but require more systematic study.
Abstract WMP59: Prognosis After Cerebral Venous Thrombosis: Long-Term Readmission Patterns in a Canadian Population-Based Cohort
Authors: Hennawy Mirna , Field Thalia S , Zhou Lily
Published: February 2024

Background:
Information on long-term care utilization patterns following the acute care period of cerebral venous thrombosis (CVT) is limited. We examined readmission reasons and patterns after discharge from index CVT hospitalization.

Methods:
A population-based cohort of patients diagnosed with CVT (2000-2017) was constructed using linked administrative data. Descriptive statistics were calculated for baseline demographics and readmission causes. Readmission proportions were calculated for first readmission every year during the 10 years after diagnosis. Survival analysis was used to examine associations between patient factors and readmission events.

Results:
The cohort included 508 patients, 56% female and mean age 49.6 years (SD 19). Median time-to-first readmission is 1.8 years (95% CI 1.4-2.4), with 39% of patients readmitted in 1 year (95% CI 35-43) and 69% in 5 years (95% CI 64-73). Cancer-related CVT was associated with a higher rate of readmission (p<0.0001) and traumatic CVT was associated with a lower rate (p=0.005). In patients younger than age 50 (mean: 36.1 years, SD 9), headache and epilepsy were among the top five reasons for readmission. For patients older than 50 years (mean: 67.6 years, SD 11), cerebral infarction was among the top five reasons. Readmission rate stabilized over time.

Conclusion:
Cancer-related CVT was associated with significantly higher readmissions and traumatic CVT had significantly lower readmissions. The most common neurologic reasons for readmission differed by age group, but included headaches, seizures, and stroke. Readmission rates were highest in the first two years following discharge but stabilized over time.
Abstract WMP76: Long-Term Effects of Intracerebral Hemorrhage on Behavior and Inflammation
Authors: Abramson Efrat , Cooper Dawson , Sansing Lauren H
Published: February 2024

Introduction:
Intracerebral hemorrhage (ICH) survivors remain at high risk for progressive cognitive impairment and post-stroke depression. However, little is known about the contribution of chronic neuroinflammation and sex-specific differences to behavioral changes at late timepoints.

Methods:
ICH was induced in 3-month male and female C57BL/6J wild type mice by injecting 0.8μL of type VII collagenase into the right striatum. Mice were perfused on day 0 (naïve) and day 28 following ICH, and the perihematomal region harvested for microglia isolation on a FACSAria. Transcriptomics was analyzed using nCounter Digital Analyzer using a custom neuroinflammation panel. Social deficits and cognition were measured via the 3-chambered sociability test at 0, 28, and 60-days post-ICH.

Results:
GO Biological Processes revealed that type I interferon signaling genes comprised the top three upregulated gene sets (adjusted P value < 10
-5
) when compared to naïve microglia, suggesting a continued inflammatory response 28 days following ICH. As expected, behavioral analysis showed no sociability differences between males (N=4) and females (N=3) at day 0 (p = 0.1313). Males did not show an overall decline in sociability at day 28 or day 60 when compared to day 0 (p > 0.05, N= 5, 4). However, females showed a progressive decrease in sociability that became significant at day 60 (p = 0.032, N= 3). Interestingly, females spent significantly less time with the novel mouse (p = 0.019) and more time in the nonsocial chambers when compared to males at day 60 (p = 0.030).

Conclusions:
Our findings suggest that there is a chronic inflammatory signature long after the initial cell response to ICH which may be promoting long-term behavioral deficits in a sex-specific manner. As type I interferons have been increasingly linked to mood disorders, understanding the relationship between chronic inflammation, mood, and sex-specific differences will be crucial.
Abstract WMP77: In-Hospital Mortality Sex Differences in Young Adults With Intracerebral Hemorrhage
Authors: Cadena Angel , Haghighi Noora , Sariyeva Mehriban , Valdes Eduard , Connolly E. Sander , Agarwal Sachin , Park Soojin , Ghoshal Shivani , Claassen Jan , Roh David , Miller Eliza C
Published: February 2024

Introduction:
Intracerebral hemorrhage (ICH) accounts for 10-20% of strokes and is associated with severe disability and high mortality. While males are reported to have worse outcomes in older patients with ICH, data are limited regarding sex differences in mortality risk after ICH for younger patients.

Methods:
We conducted a cross-sectional study of 134 adults aged 18-44 admitted to our academic medical center with ICH from 01/01/2012-12/31/2021, using data from an internal stroke registry and the Intracerebral Hemorrhage Outcomes Project (ICHOP). All vascular and non-vascular causes were included other than trauma. We used logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between sex and in-hospital mortality, adjusting for comorbidities and presence of multicompartmental hemorrhage (including intraventricular extension).

Results:
Characteristics of the study sample are summarized in the Table. Males had higher proportion of chronic hypertension and subcortical ICH location. Adjusting for hypertension, ICH location, multicompartmental extension, and use of antiplatelet medication, males had higher odds of death (OR 4.0, 95% CI 1.1-15.4) than females. Functional outcomes at discharge are shown in the Figure.

Conclusion:
In our cohort of young adults with ICH, males had 4-fold higher odds of in-hospital death than females. Future research should investigate the social and biological mechanisms that may underlie sex differences in mortality for young adults with ICH, including differences in ICH etiology, and potentially differential withdrawal of life sustaining treatment.
Abstract WMP82: Peri-Hematomal Edema (PHE) Shape Features as Independent Predictors of the 3-month Outcome in Acute Supratentorial Intracerebral Hemorrhage (ICH)
Authors: Dierksen Fiona , TRAN ANH TUAN , Zeevi Tal , Qureshi Adnan I , Malhotra Ajay , Werring David J , Sanelli Pina C , Falcone Guido J , Sheth Kevin N , Payabvash Sam
Published: February 2024

Background:
Perihematomal edema (PHE) is a marker of post-ICH secondary brain injury and a potential treatment target. However, different studies have reported equivocal results regarding the optimal metrics of PHE volume in relation to clinical outcomes - such as absolute, and relative baseline PHE volume, or the rate of PHE volume growth over the first 24- and 72-hours post-ICH. In this study, we examined the association of different PHE shape features at baseline and 24-hour with outcome at 3-month follow-up.

Methods:
We used the data from ATACH-2 trial. We manually segmented ICH and PHE on baseline and follow-up CTs, and extracted 14 shape features. We explored the association of baseline, follow-up, difference (baseline subtracted from follow-up) and temporal rate (difference divided by time gap) of PHE shape changes with 3-month mRS. We applied Spearman correlation to assess univariate associations, and multivariate stepwise regression to evaluate if PHE shape features independently predict outcome adjusting for age, sex, NIHSS, GCS, baseline ICH volume, and treatment.

Results:
796 patients were included. Baseline PHE maximum diameters across various planes, main axes, volume, surface and sphericity correlated with 3-month mRS after adjusting for multiple comparisons. The 24-hour difference and temporal change rates of these features also had significant association with outcome - but not the 24-hour absolute values. In multivariate regression, baseline PHE shape sphericity (p=0.029) and voxel volume (p=0.026), alongside admission NIHSS (p< 0.001), ICH volume (p=0.002), and age (p<0.001) were independent predictors of favorable outcomes.

Conclusion:
Aside from metrics of volume, PHE sphericity at baseline is an independent prognostic factor, with less spheric (more irregular) shape associated with worse outcome. In addition, baseline PHE shape features - compared to changes over the first 24 hours post-ICH - had stronger prognostic associations.
Abstract WMP89: Reperfusion Pattern as a Predictor of Final Infarct Growth in Patients With Anterior Large Vessel Occlusion Ischemic Stroke
Authors: Rodrigo-Gisbert Marc , Canals Pere , Garcia-Tornel Alvaro , Requena Manuel , Rizzo Federica , Olive-Gadea Marta , Muchada Marian , Tanzi Leonardo , Marti Cristian , Salvia Punsoda Victor , Ribo Marc
Published: February 2024

Aim:
The first pass effect (FPE) and complete sudden recanalization (cSR) have been identified as an indicator of favorable clinical outcome. We aimed to compare final infarct volume (FIV) according to different reperfusion pattern.

Methods:
We included consecutive patients admitted with an anterior LVO stroke (intracranial internal carotid artery, MCA-M1) who underwent endovascular treatment between January 2018 and April 2022. Patients with partial or no-reperfusion (eTICI 0-2b) were excluded. Final complete reperfusion (TICI 2c-3) was categorized as achieved at first pass (FPE) or in subsequent passes as sudden (cSR: from TICI 0-1 to TICI 2c-3 in a single pass) or progressive (PR: interim partial recanalization). FIV was quantified using an automatic segmentation tool (Methinks AI) on 24-hour NCCT. Aggregated infarct distribution heatmaps were generated to compare FIV distribution.

Results:
Of 316 consecutive patients, complete reperfusion was achieved in 202 patients (63.9%). Reperfusion patterns were as follows: FPE (109/202, 54.0%), cSR (28/202, 13.9%) and PR (65/202, 32.1%).

The mean FIV was 28.1mL (95%CI 19.1-37.1), 49.5mL (95%CI 18.8-80.2) and 58.4mL (95% CI 37.6-79.2) in FPE patients, cSR and PR patients, respectively (p=0.014). After adjusting for confounders, FPE and cSR patterns were independently associated with a reduced FIV (FPE: -61.7%, 95%CI -77.2% to -35.8%, p<0.001; cSR: -39.7%, 95%CI -63.8% to 0.6%, p=0.05).

The rate of excellent clinical outcome (mRS 90d 0-1) was higher in FPE (36.1%) and cSR (35.7%) groups compared to the PR group (20.3%, p=0.081).

Conclusion:
Improved clinical outcomes in patients with FPE and cSR patterns seem to be influenced by reduced infarct volume in a stepwise manner (FIV FPE<cSR<PR). PR may reflect clot fragmentation and embolization, contributing to infarct growth and worse outcomes. Reperfusion patterns should be explored for selecting target populations for adjunctive neuroprotective therapies during EVT.
Abstract WMP93: Door-to-Thrombolysis Time Between Primary Stroke Centers and Comprehensive Stroke Centers: Is There an Added Benefit?
Authors: Henkel Nicholas , Alhajala Hisham , Jumaa Mouhammad A , Zaidi Syed F
Published: February 2024

Introduction:
Comprehensive Stroke Centers are skilled, highly trained facilities that provide advanced care to an array of stroke patients. If stroke patients are not able to reach a Comprehensive Stroke Center, Primary Stroke Centers provide convenient and rapid care to patients presenting with acute ischemic stroke. Ideally, these Primary Centers save time to intervention. Whether there are differences in time to intervention, and resultant patient outcomes, between such centers has not been thoroughly studied. To this end, we examined door-to-needle and door-to-stroke alert time between one Comprehensive Stroke Center and three Primary Stroke Centers in Northwest Ohio.

Hypothesis:
Primary Stroke Centers will have longer time to intervention (i.e., door-to-needle times) than that of Comprehensive Stroke Centers.

Methods:
From 2018-2023, we examined door-to-needle and door-to-stroke alert times in patients presenting to the ProMedica Health System with ischemic stroke in a retrospective chart review. All patients presented with Large Vessel Occlusion (LVO) ischemic stroke.

Results:
293 patients and 255 patients presented to either the Primary Centers or the Comprehensive Stroke Center, respectively. Door-to-needle time was significantly longer in patients presenting to the Primary Centers (Median: 59.00 minutes), compared to the Comprehensive Stroke Centers (Median: 39.50) (Mann Whitney U-Test: p <0.0001). However, door-to-stroke alert was not different between the two centers (Primary, Median: 2; Comprehensive, Median: 1, Mann Whitney U-Test: p = 0.099).

Conclusions:
We report a longer latency to needle in Primary Stroke Centers compared to Comprehensive Stroke Centers, with no change in door-to-stroke alert time. It is forthcoming whether this difference impacts patient outcome measures. Such findings suggest that stopping at Primary Stroke Centers may not provide either a time- or outcome-benefit in lieu of immediate arrival to a Comprehensive Stroke Center.
Abstract WMP94: Quantifying the Enhanced Clinical Benefit of Endovascular Thrombectomy Performed With Contemporary Workflows and Devices
Authors: Tariq Muhammad Bilal , Saver Jeffrey L
Published: February 2024

Background:
To date, the magnitude of the benefit of endovascular thrombectomy (EVT) over medical management in acute ischemic stroke has been quantified by the data of the five breakthrough RCTs of 2015. But contemporary EVT care has faster EVT workflow speeds and achieves higher rates of reperfusion. Updated quantitative estimates of the benefit of EVT vs medical management are needed.

Methods:
Contemporary FDA-monitored (TIGER/ARISE II) and pivotal (HERMES) EVT trial group differences were quantified for workflow speed (door-to-reperfusion time) and reperfusion rates (eTICI distribution). The projected effect of the faster workflow speed in further improving disability (mRS) outcomes were calculated using established HERMES treatment time-benefit models and the projected effect of higher reperfusion rates using established HERMES eTICI tier-specific outcomes.

Results:
Contemporary EVT trial groups, compared with pivotal trial EVT groups, had door-to-reperfusion 57 minutes faster (146m vs 89m), successful reperfusion 22.6% more often (71.0% vs 93.6%), and excellent reperfusion 45.1% more often (29.4% vs 74.5%). Figure 1 shows the resulting projected improvements in mRS distributions. For functional independence (mRS 0-2), outcome rates for MM vs pivotal EVT vs contemporary EVT were 25.2% vs 44.6% vs 74.5%. The number needed to treat (NNT) for 1 more patient to achieve functional independence improved from 5.2 to 2.5. For nondisabled outcome (mRS 0-1), outcome rates were 10.1% vs 27.4% vs 46.0%. The NNT for 1 more patient to achieve nondisabled outcome improved from 5.8 to 2.8. Over the entire mRS range, the NNT for 1 more patient to have less disability by at least one mRS level improved from 2.6 to 1.6.

Conclusion:
Formal modeling indicates that contemporary EVT confers substantially enhanced benefits over medical management. Among every 100 patients treated with EVT, 63 will have a less disabled long-term outcome including 36 more becoming disability-free.
Abstract WP104: Updating Cost-Effectiveness of Stroke Thrombectomy in Patients With Large Core Ischemic Stroke Using 2023 Clinical Trial Data
Authors: Kao Szu-Yu Zoe , Sangha Kinpritma , Sanmartin Maria , Siddiqui Adnan H , Mocco J D , Hui Ferdinand , Hochrein Patrick , Sanelli Pina C , Eusemann Christian , Turner Raymond
Published: February 2024

Introduction:
Stroke thrombectomy (ST) is cost-effective for acute ischemic stroke (AIS) patients with large-vessel occlusion and low Alberta Stroke Program Early CT Score (ASPECTS <6) compared with non-endovascular standard care (SC). However, previous cost-effectiveness analyses (CA) were based on data that were not specific to low ASPECTS or had limited generalizability (e.g., data on Japanese patients with ASPECTS 3-5). As new results from two 2023 clinical trials that included patients with ASPECTS <6 emerged from Western countries and China, we aim to update the cost-effectiveness of ST using new data from different populations and assess how ST treatment delay might affect the comparative effectiveness of ST and SC.

Methods:
We updated the cost-effectiveness of ST compared with SC in AIS patients aged 67 years with ASPECTS <6 based on the data from two trials conducted in Western countries and China using a previously published Markov model that simulates the lifetime cost and quality-adjusted life years (QALYs) with annual cycles. The difference between ST and SC was characterized by the patient distribution of modified Rankin Scales at 90 days after hospital discharge (90-day mRS) as reported from the two trials. We conducted two separate CA at a willingness-to-pay threshold of $100,000/QALY using the 90-day mRS distribution from each trial with the ST treatment delay as observed in the trials (base case). In addition, we assessed how the effectiveness of ST varied with ST treatment delay up to 6 hours in addition to the observed delay in trials.

Results:
In the base case, irrespective of two trial datasets, ST is a dominant strategy that saved $8,431-$32,083 and nearly 1 QALY with a positive net monetary benefit (NMB) compared to SC, which had a negative NMB. Regarding ST treatment delay, the QALYs generated from ST decreased as additional treatment delay increased. If the additional ST treatment delay was within 2-3.5 hours, ST could generate more QALYs and was still cost-effective compared to SC.

Conclusions:
Our findings suggest ST is the preferred strategy over SC in AIS patients with low ASPECTS. ST remains effective and cost-effective even when ST is delayed beyond the median transfer time of 174 minutes in the U.S. reported in Stamm et al. JAMA study.
Abstract WP111: Stroke Team Member Perspectives on Factors That Influence Hospital Door-to-Needle Time Performance: A Qualitative Analysis
Authors: Oostema John A , Nickles Adrienne
Published: February 2024

Background:
Despite substantial to minimize ischemic stroke treatment delays, hospital door-to-needle (DTN) time variations persist. We sought to identify sources of variation in practice as well as understand stroke team member perceptions of factors that influence DTN performance in a sample of hospitals that participate in a statewide stroke registry.

Methods:
We conducted a series of semi-structured interviews with stroke coordinators and emergency department (ED) staff. Participants were invited from hospitals with the fastest or slowest DTN times in 2022. Transcripts of the interviews were coded to identify differences in hospital acute stroke code processes as well as interviewee perceptions of facilitators and barriers to optimal performance.

Results:
Ten individuals from 6 hospitals participated in interviews (6 stroke coordinators, 3 ED physicians, 1 ED nurse). Variations in stroke code processes included location of initial patient evaluation, stroke team composition (inclusion of pharmacy or in-person neurology provider), imaging strategy for large-vessel occlusion stroke screening, thrombolytic medication utilized, and team members primarily responsible for thrombolytic decision-making, mixing, and delivery. Common facilitators of rapid DTN times included integration of EMS, multidisciplinary engagement with quality improvement teams (especially physician engagement), embedding critical care nurses in stroke teams, and providing rapid, individualized feedback to clinical personnel. Common barriers included identifying stroke in triage, staff turnover, and inadequate stroke coordinator resources. Participants from higher performing hospitals reported having larger stroke teams with in-person neurology support. Participants from lower performing hospitals highlighted staffing shortages and difficulties with video-based teleneurology.

Conclusion:
Stroke code process variation is common and largely driven by hospital resources. Highly engaged, physician-led multidisciplinary teams and timely, actionable feedback were seen as key elements of achieving DTN goals. Staffing shortages and lack of access to timely neurological consultation are system-level barriers to optimal stroke care.
Abstract WP12: Early or Later Anticoagulation in Post-Stroke Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Narciso Igor A , Tatsch Terres Marcela , Faria Nathalia , Cocato Malagutti Beatriz , Melo Soares Pinho de Carvalho Lara , Ribeiro Adriele , Mendes Bárbara
Published: February 2024

Introduction:
Uncertainty regarding the timing of anticoagulant initiation after an ischemic stroke in patients with atrial fibrillation arises from the lack of extensive data on this matter. We conducted the first meta-analysis, including only randomized controlled trials, to clarify this question.

Methods:
We systematically searched Embase, PubMed, and Cochrane Library in June 2023 for studies comparing early versus late initiation of anticoagulation post-stroke in patients with atrial fibrillation. Statistical analyses were performed using R software version 5.4.1.

Results:
We included three studies comprising 2,989 patients. Of these, 1,497 (50%) received early anticoagulation with a direct oral anticoagulant (DOAC), and 1,492 (50%) received later anticoagulation with a DOAC or warfarin. 51.66% of participants were women. The use of early anticoagulation was associated with a lower incidence of recurrent ischemic stroke; nonetheless, this result lacked statistical significance (RR 0.68; 95% CI 0.44-1.04; p=0.07; I
2
=0%). The number of symptomatic intracerebral hemorrhage events was 2 in the early anticoagulation group and 3 events in the later anticoagulation group, with no statistical significance between the groups.

Conclusion:
Our findings suggest no statistically significant difference in recurrent ischemic stroke and intracerebral bleeding between the initiation of early or later anticoagulation in post-stroke patients with atrial fibrillation.
Abstract WP121: Cerebral Hemodynamics in the First Week Postpartum in Healthy Women and Women With Preeclampsia
Authors: van Wingerden Anne-Sophie , Katsidoniotaki Maria , Haghighi Noora , Almonte Casandra , Woolcock Helen , Valdes Eduard , Alian Aymen , Booker Whitney , Bello Natalie A , Kougioumtzoglou Ioannis , Marshall Randolph , Petersen Nils H , Miller Eliza C
Published: February 2024

Objective:
Standard adult normative data for transcranial Doppler (TCD)-based cerebral hemodynamic measures, such as mean and peak cerebral blood flow velocity (mCBFV, pCBFV), are used to identify pathological conditions such as postpartum angiopathy. However, little is known about cerebral hemodynamics during the early postpartum period, particularly in patients with preeclampsia (PEC). We characterized cerebral hemodynamics using TCD in the first week postpartum in patients with and without PEC.

Methods:
We prospectively recruited women with PEC and normotensive pregnant women delivering at an urban academic medical center. We measured CBFV in the bilateral middle cerebral arteries with TCD and calculated systolic mCBFV and pCBFV as well as pulsatility index (PI) and PI-derived noninvasive intracranial pressure (nICP). We compared systolic mCBFV and pCBFV between postpartum women with and without PEC, and historical data from non-pregnant young adult female controls.

Results:
Subjects were 51 women with PEC, 19 normotensive postpartum women, and 28 non-pregnant historical controls. In the PEC group, median mCBFV was 75.0 cm/s (IQR 65.2-99.1) and median pCBFV was 106.9 cm/s (IQR 92.7-130.8). In the normotensive postpartum group, median mCBFV was 77.1 cm/s (IQR 66.0-92.3) and median pCBFV was 107.9 cm/s (IQR 96.6-127.4). In the non-pregnant female control group, median mCBFV was 62.0 cm/s (IQR 48.5-67.9) and median pCBFV was 83.6 cm/s (IQR 69.3-95.2) (p<0.0001 for mean and peak 3-way comparisons; see Figure). PI and nICP were within normal range in both postpartum groups and did not differ significantly between groups.

Conclusion:
Postpartum women with and without PEC had mCBFV and pCBFV significantly higher than non-pregnant controls, and many fell outside the standard normal range for healthy adults, but PI and nICP were within normal range. Standard ranges of CBFV for healthy adults may not apply in the postpartum period.