bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 68:
FOXO3
Longevity Genotype Attenuates the Impact of Hypertension on Microinfarct Risks
Authors: Nakagawa Kazuma , Chen Randi , Ross G. Webster , Willcox Bradley , Donlon Timothy A , Allsopp Richard , Willcox Craig , Morris Brian J , Masaki Kamal
Published: February 2024

Background:
The
G
allele of
FOXO3
SNP
rs2802292,
which is associated with human resilience and longevity, has been shown to attenuate the impact of hypertension on the risk of intracerebral hemorrhage. We sought to determine whether the
FOXO3 G
-allele similarly attenuates the impact of hypertension on the risk of cerebral microinfarcts (CMI).

Methods:
From a prospective population-based cohort of American men of Japanese ancestry from the Kuakini Honolulu Heart Program (KHHP) and Kuakini Honolulu-Asia Aging Study (KHAAS) that had brain autopsy data, age-adjusted prevalence of any CMI on brain autopsy was assessed. Logistic regression models, adjusted for age at death, cardiovascular risk factors,
FOXO3
and
APOE-
ε
4
genotypes, were utilized to determine the predictors of any CMI. Interaction of
FOXO3
genotype and hypertension was analyzed.

Results:
Among 809 men with complete data, 511 (63.2%) participants had evidence of CMI. A full multivariable model demonstrated that body mass index (OR=1.07, 95% CI=1.01-1.14,
P
=0.012) was the only predictor of CMI, while hypertension was a borderline predictor (OR=1.44, 95% CI=1.00-2.08,
P
=0.052). However, a significant interaction between
FOXO3 G
-allele carriage and hypertension was observed (
P
=0.020). In the stratified analyses, among the participants without the longevity-associated
FOXO3 G
-allele, hypertension was a strong predictor of CMI (OR=2.25, 95% CI=1.34-3.77,
P
=0.0021), while among those with the longevity-associated
FOXO3 G
-allele, hypertension was not a predictor of CMI (OR=0.88, 95% CI: 0.51-1.54,
P
=0.66).

Conclusions:
The longevity-associated
FOXO3
G
-allele mitigates the impact of hypertension on the risk of CMI.
Abstract 70: Rich-Club Behaviour and Analyses in the Human Brain Connectome as Novel Early Biomarkers of Cognitive Decline
Authors: Tadros George S , Guo Jen , Reaume Noaah , Towlson Emma K , Barber Philip A
Published: February 2024

Introduction:
Transient ischemic attack (TIA) patients have an increased risk of early dementia, but the mechanism is unclear. One potential mechanism is the damaging effects of microvascular disease on brain networks. Rich club is a phenomenon where highly connected nodes form a “rich club” amongst themselves, thus playing an important role in global brain network communication. In this study we aim to determine 1) whether the prominence of the rich club effect declines greater in TIA patients than controls over time, and 2) the relationship of rich club prominence with cognition.

Methods:
TIA patients (n=47) and controls (n=43) underwent DTI imaging and cognitive assessment at baseline, 1-year, 3-year, and 5-year. Whole-brain tractography utilizing constrained spherical deconvolution was performed to construct whole-brain connectomes for both groups at all available timepoints. The maximum normalized rich club coefficient (Φ
max
) was used as an indicator of the prominence of the rich club effect. Independent-sample T-tests were used to compare Φ
max
cross-sectionally, while a linear mixed effect (LME) model was used to examine the longitudinal change in Φ
max
in TIA patients vs. controls, while controlling for covariates including age, sex, WMH volume, whole-brain volume, and peak width of skeletonized mean diffusivity.

Results:
TIA patients had a mean age of 63.94 (
SD
=8.62) and 20 females. Controls had a mean age of 60.73 (8.16) and 29 females. The prominence of the rich club was not significantly different between TIA patients and controls at baseline or 1-year (
p
>0.05). However, TIA patients showed a significantly less prominent rich club at 3-year and 5-year compared to controls (
p
=0.047 and 0.018, respectively). TIA patients exhibited a significantly greater decrease in rich club prominence over time, relative to controls (
p
=0.023), after accounting for covariates. Longitudinal LME models showed no association between changes in rich club prominence and changes in cognition (
p
>0.05 for all cognitive domains).

Conclusion:
In this study, we show a decrease in rich club prominence in TIA patients compared to controls which might identify their increased risk of cognitive impairment, and the potential benefits of aggressive vascular risk reduction.
Abstract 8: Polygenic Resistance to Blood Pressure Treatment and Stroke Risk
Authors: Huo Shufan , Rivier Cyprien , Clocchiatti-Tuozzo Santiago , Renedo Daniela , Zhao Hongyu , Petersen Nils H , de Havenon Adam H , Falcone Guido J
Published: February 2024

Background:
Common genetic variation explains up to 40% of blood pressure variation. Despite this compelling physiological impact, the role of common genetic variation in blood pressure treatment and their sequelae remains understudied. We hypothesize that a higher polygenic predisposition to hypertension leads to a poorer response to blood pressure (BP) treatment and higher stroke risk in a primary prevention setting.

Methods:
We conducted a 2-stage genetic association study using data from the All of Us Research Program (discovery stage) and UK Biobank (replication stage). We included participants on any BP medication at enrollment and excluded those with prior stroke. Participants were categorized as having low, intermediate, or high polygenic predisposition to hypertension according to percentiles (<20, 20-80, >80) of a polygenic risk score of 177 independent risk variants. Uncontrolled systolic BP was defined as >140mmHg and incident stroke was ascertained using Electronic Health Record data and ICD 9/10 codes. We used multivariate logistic and Cox Proportional Hazards regressions, as appropriate, to assess the relationship between genetic predisposition to hypertension and both uncontrolled BP and incident stroke.

Results:
The discovery stage included 110,892 participants (mean age 58, female sex 58%). Compared to low polygenic risk, intermediate and high risk were linked with 14% (OR 1.14, 95%CI 1.10-1.18) and 30% (OR 1.30, 95%CI 1.24-1.36) surge of uncontrolled BP risk (p<0.001). Similarly, compared to low polygenic risk, intermediate and high risk were associated with 8% (HR 1.08, 95%CI 0.97-1.20) and 15% (HR 1.15, 95%CI 1.00-1.30) increments in stroke risk (p=0.04). These results were replicated in 102,252 participants (mean age 61, female sex 47%) enrolled in the UK Biobank (p<0.05 for both analyses).

Conclusions:
Among participants on antihypertensive medications, increased genetic predisposition to hypertension correlated with higher risk of uncontrolled BP and stroke. As All of Us and direct-to-consumer companies return genomic information to millions of Americans, our findings support further research, including clinical trials, to explore personalized treatments targeting high-risk subjects for intense interventions.
Abstract 84: Efficacy of Endovascular Therapy in Acute Ischemic Stroke by Alberta Stroke Program Early Computed Tomography Score and National Institutes of Health Stroke Scale-A Secondary Analysis of a Randomized Controlled Trial
Authors: Zheng Lina , Nie Ximing , Wang Mengxing , Pan Yuesong , Zhongrong Miao , Liu Liping
Published: February 2024

Introduction and Aims:
The ANGEL-ASPECT trial demonstrated the effectiveness of endovascular therapy (EVT) in acute ischemic stroke (AIS) patients with large infarct. We did a secondary analysis to explore the efficacy of EVT according to Alberta Stroke Program Early Computed Tomography Score (ASPECT) and National Institutes of Health Stroke Scale (NIHSS).

Methods:
ANGEL-ASPECT trial was a randomized clinical trial involving patients with acute anterior-circulation large-vessel occlusion and an ASPECT score of 3-5 or an infarct-core volume of 70-100ml. Patients were randomly assigned to EVT or standard medical treatment (SMT) alone. We categorized patients based on the combination of ASPECT (≤3 or 4-5) and NIHSS (<20 or ≥20) into four groups: low ASPECT & low NIHSS; low ASPECT & high NIHSS; high ASPECT & low NIHSS and high ASPECT & high NIHSS. We assessed the efficacy of EVT using ordinal shift analysis of 90-day modified Rankin Scale (mRS).

Results:
Among 455 patients, the prevalence of the four groups were 190 (41.8%), 70 (15.4%), 157 (34.5%) and 38 (8.4%), respectively. A significant shift in the distribution of 90-days mRS toward better outcomes in favor of EVT was observed in patients with low ASPECT & low NIHSS (common OR [cOR], 2.25; 95% CI, 1.34-3.76; P=0.002), and high ASPECT & low NIHSS (cOR, 2.30; 95% CI, 1.31-4.05; P=0.004), but not in other two groups with high NIHSS (all P >0.05).

Conclusions:
EVT was associated with better outcomes in AIS patients with large infarct and mild-to-moderate stroke severity (NIHSS <20), but not in those with severe stroke severity (NIHSS ≥20). Stroke severity should be considered when planning EVT for AIS patients with large infarcts.
Abstract 9: Efficacy of Colchicine for Prevention of Stroke and Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease: A Meta-Analysis of 15 Randomized Controlled Trials
Authors: Kalra Kriti , Jaiswal Vikash , Jaiswal Akash , Chia Jia Ee , Ang Song Peng , Raj Nishchita , Wajid Zarghoona
Published: February 2024

Background:
Clinical evidence supports the role of Inflammation in atherosclerosis and associated complications. Colchicine as a potential anti-inflammatory treatment among such patients has attracted much attention in recent years. However, its efficacy on cerebrovascular and cardiovascular events is still controversial.

Objective:
We sought to evaluate the efficacy of Colchicine for coronary artery disease patients.

Methods:
We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until August 30th, 2023. Odds ratios (OR) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant.

Results:
A total of 15 randomized controlled trials were included (6863 in Colchicine and 6756 in the control group) in the analysis. Pooled analysis of primary and secondary endpoints showed that Colchicine significantly reduced the risk of incidence of stroke by 50% (OR, 0.50 (95%CI: 0.31-0.81), P>0.001), myocardial infarction by 40% (OR, 0.60 (95%CI: 0.44-0.84), P>0.001), new acute coronary syndrome by 53% (OR, 0.47(95%CI: 0.47-0.85), P>0.001), and major adverse cardiovascular events 45% (OR, 0.55(95%CI: 0.39-0.78), P>0.001) compared with control. However, the risk of all-cause mortality (OR, 1.06(95%CI: 0.83-1.35), P=0.55) was comparable between both groups of patients.

Conclusion:
Colchicine was associated with an overall reduction in the risk of incidence of stroke, MI, MACE, ACS in patients with coronary heart disease. However, no such effect was observed with mortality.
Abstract HUP10: Sex Disparities In A Telestroke Network: From Treatment Times To Outcomes
Authors: Hanna McKay , Sam Henry , Gregoski Mathew , Wabnitz Ashley M , Al Kasab Sami , Larson Katharine , Holmstedt Christine A , Grewal Parneet
Published: February 2024

Background:
The structure of the stroke care delivery system in rural South Carolina has been changed by the Medical University of South Carolina tele-stroke program with >40 spoke sites with improved treatment times and outcomes overall. Disparities at the level of primary stroke centers and acute stroke ready hospitals have not been well studied. The aim of this study is to retrospectively analyze data from the tele-stroke network for sex differences in stroke care processes at spoke sites to identify disparities in treatment times and outcomes between men and women.

Methods:
Data was collected and analyzed for 21,549 patients between 1/1/2012 and 12/31/2022 for whom a telestroke was paged out. Statistical analysis was completed using SPSS version 28 (IBM corporation, Armonk, NY). Variables with continuous outcomes were assessed using independent samples median tests and categorical variables were assessed using X
2
.

Results:
Of 10,713 (49.7%) males and 10,836 (50.3%) females, females were older (68.29±15.5 vs 66.09±13.7, p<0.01) and more likely to be to be African American (20.4% vs16.8%, p<0.05) as compared to males. Females were more likely to get thrombolytic therapy (29.06% vs 27.2%, p<0.05) but there was no difference in endovascular therapy between both sexes. Treatment times showed that door-to-registration timing (F: 18±27 vs M: 17±26, p<0.05) and door to telestroke page timing (F: 22±27 vs M: 20±26, p<0.05) was significantly higher in females compared to males with ultimately door to needle time having the expected disparity between men and women (F: 59±36 vs M: 55±35, p<0.05). Women also had significantly higher mean discharge NIHSS (M: 4.17±6.20 vs F: 4.61±6.70 (p<0.001) and mRS score (M:2.24±1.93 vs F:2.43±1.95 (p<0.001)). More males were discharged home (62.4% vs 60.4%, (p<0.001) and more females were discharged to nursing home (8.1% vs 6.2%, p<0.001) and hospice (3.9% vs 2.9%, p<0.001) post admission.

Conclusions:
Females are older at the time of stroke onset, have longer times to treatment and poorer outcomes and discharge dispositions. Our findings highlight the opportunities to ameliorate sex disparities in developing telestroke networks in the United States. Future studies should target these disparities to improve outcomes.
Abstract NS2: An Expedited Transfer Process Improves Door In Door Out Times
Authors: Owens Karrima , Blum Christina , Cort Mark , Sellers Michele , Novello Paul , McPartland Ellen , Hoey Colin , Rothstein Aaron , Stein Laura A
Published: February 2024

Background:
Rapid reperfusion with mechanical thrombectomy for ischemic stroke secondary to large vessel occlusion leads to significant reduction in morbidity and mortality. DIDO time is an important metric for stroke centers without on-site mechanical thrombectomy. Delays in treatment can occur when patients present at a Primary Stroke Center (PSC) then require transfer to the CSC for MT. Our system Comprehensive Stroke Center (CSC) receives patients from 2 of our system’s PSCs. In order to expedite care an expedited transfer protocol was implemented.

Purpose:
The goal of this work is to decrease the time at the PSC, known as door-in-door-out (DIDO), and decrease overall time from patient presentation to treatment with thrombectomy.

Methods:
Patients are screened at triage by a PSC emergency department provider for the following: aphasia, gaze preference, or neglect with unilateral weakness within 24 hours of last known normal. If these criteria are present, the emergency department provider contacts the CSC transfer center to initiate the expedited transfer process, which begins mobilizing resources to the PSC while clinical work-up continues. This expedited early transfer process was implemented in January 2021. Transfers for MT during the 12-month period before and after the implementation of the expedited transfer process were analyzed.

Results:
A sustained reduction in overall DIDO was observed during the time period following implementation of the expedited transfer process (Fig 1) Mean DIDO was lower when the transfer call was placed before CT vs after CT (81 min vs. 132 min respectively) (p=.0031).

Conclusions:
Use of the Expedited Transfer Process allows transfer resources to begin moving to the patient with a suspected LVO in parallel with ongoing evaluation, resulting in faster DIDO times leading to faster treatment aimed at reducing stroke morbidity and mortality. Further analysis of the effect of the expedited transfer process on DIDO times is planned.
Abstract NS8: Interventional Nurse Practitioner-Led Loop Recorder Implantation Program: Impact on Quality of Etiopathogenic Diagnosis of Ischemic Stroke
Authors: Pfeiffer Kimberley , Pond Donna S , Ingebritson Daphne , French Brandi R , Siddiq Farhan , Qureshi Adnan I , Gomez Camilo R
Published: February 2024

Background:
Extended cardiac rhythm monitoring increases the odds of detecting paroxysmal atrial fibrillation (PAF), an important finding in the etiopathogenic evaluation of patients with ischemic stroke. The development of a systematic approach to extended cardiac monitoring in this population is bound to positively influence the quality of diagnostic evaluation and, by extension, the application of tailored protocols for secondary stroke prevention.

Methods:
We retrospectively analyzed our experience with a cardiac loop recorder implantation program specifically designed for ischemic stroke patients suspected of having cardiogenic embolism, led and implemented by an interventional nurse practitioner in our team. We specifically queried its diagnostic yield as it relates to the quality of etiopathogenic diagnosis of this population.

Results:
The program has been currently in operation for 21 months, during which, 103 patients have undergone successful implantation of a cardiac loop recorder. The cohort includes 54 women and 49 men, their ages ranging 39-89 years (Mean = 67), 90 (87.38%) of whom had suffered an ischemic stroke, while the remainder had transient ischemic attacks. A total of 12 (11.65%) patients had newly detected PAF during the monitoring period, which varied 12-612 days (Mean = 316). The interval from implantation to PAF detection varied 3-202 days (mean = 90). Only one (0.97%) procedural complication (i.e., site infection) occurred, requiring device explantation without any long-term effects. All instances (100%) of PAF detection resulted in a change in from antiplatelet to anticoagulant agents for secondary stroke prevention.

Conclusions:
Programmatic implantation of cardiac loop recorders can successfully be carried out by interventional nurse practitioners, and it effectively enhances the etiopathogenic evaluation of ischemic stroke patients. Moreover, its yield for detection of PAF is considerable, and it translates in measurable changes in preventive antithrombotic regimens.
Abstract TMP101: Statewide Burden and Trends of Stroke Attributable to High Systolic Blood Pressure in the United States From 1990-2019: A Benchmarking and Comparative Analysis
Authors: Cortorreal Javier Rafael , John Jobby , patel Anandkumar , Uppaluri Srikar , Sakhamuri Lakshmi Tejaswi , Dadhania Khush , Chhayani Hiren , Brahmbhatt Niki , Sojitra Vani , Gadamidi Vinay Kumar , Thota Anjani Kumar , Desai Hardik Dineshbhai
Published: February 2024

Background:
Stroke ranks as the 5th leading cause of deaths across all casualties within the United States (US).

Hypothesis:
Nevertheless, a comprehensive and uniform assessment of the statewide burden of stroke attributable to high systolic blood pressure (SBP), has hitherto remained absent.

Method:
Using Global Burden of Disease framework, mortality and disability-adjusted life years (DALYs) of Stroke attributable to high SBP were analyzed by age, sex, year across the US from 1990-2019.

Result:
The overall count of deaths experienced a decline from 81,237 (95% UI: 65,781-97,400) in 1990 to 80,997 (95% UI: 62,112-102,290) in 2019. Conversely, the burden of DALYs exhibited an upward trend, from 1,674,110 (95% UI: 1,423,291-1,943,035) in 1990 to 1,722,555 (95% UI: 1,392,242-2,046,073) in 2019. Geographically, Nevada observed the highest annual percentage of change (APC) in age-standardized mortality rate (ASMR) at 133%, followed closely by Alaska at 127% from 1990-2019. Analyzing the age standardized DALYs (ASDALR), Nevada also saw the highest APC at 118% from 1990-2019. Across the three decades, females bore a greater burden of stroke attributed to high SBP compared to male counterparts. Evaluating the distribution across age groups, the most prominent APC in total deaths was observed within the 95+ age group at 104%.

Conclusion:
Of note, stroke attributable to high SBP accounted for 42.75% of all deaths attributable to stroke in 2019. By addressing this preventable risk factor through targeted interventions, there exists a tangible opportunity to alleviate the burden of stroke, thereby enhancing public health and well-being on a national scale.
Abstract TMP113: RNA Sequencing Reveals Novel Pericytic MiR-15a/16-1 Targets in Post-Stroke Cerebral Angiogenesis
Authors: Sun Ping , Li Shun , Qiu Na , Xiong Tianqing , Huang Xinlei , Zhou Chao , Wang Jiefei , Chang Alexander , Chandran Uma R , Yin Ke-Jie
Published: February 2024

Introduction:
Angiogenesis actively contributes to post-stroke functional recovery and improves long-term survival in stroke patients. Previously, we demonstrated that endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis by enhancing classic pro-angiogenic factors and their receptors, and genetic deletion of miR-15a/16-1 in pericytes likewise promotes post-stroke functional recovery by stimulating cerebral angiogenesis. Here, we further investigate the underlying mechanisms and downstream targets of pericytic miR-15a/16-1 in cerebral angiogenesis after ischemic stroke.

Methods:
Pericyte-miR15a/16-1 conditional knockout mice (Pericyte-miR-15a/16-1 cKO) and wild-type (WT) controls were subjected to 1h MCAO followed by 7d reperfusion. Cerebral microvessels were extracted and subjected to RNA-seq to identify the significant differentially expressed genes (DEGs) that related to miR-15a/16-1 and angiogenesis among experimental groups. TargetScan and miRDB were used to predict potential miR-15a/16-1 downstream targets. Primary mouse brain vascular pericytes (mBVPs) were treated with lentivirus to achieve loss- or gain-of-miR-15a/16-1 function, and subjected to OGD 8h and reperfusion 24h. Pro-angiogenic factors were further verified by dual-luciferase reporter assay, qPCR, and western blotting.

Results:
RNA-seq analysis showed 289 upregulated genes (P < 0.05 & at least one CPM > 1) and 399 upregulated genes from 100 positive enriched gene sets (GESA) in cerebral microvessels of pericyte-miR-15a/16-1 cKO mice compared to WT controls 7d after MCAO. By comparing to miR-15a/16-1 potential target database from TargetScan and miRDB, 9 angiogenic genes were identified. Further biochemical analysis revealed that Pappa2, Fgf9, Islr, and Ccr2 mRNA and protein expression are significantly increased in cerebral microvessels of cKO mice and mBVPs with loss-of-miR-15a/16-1 function. Furthermore, dual-luciferase assay results verified that loss- or gain-of-miR-15a/16-1 function significantly increased or decreased luciferase reporter activity of these four genes, respectively.

Conclusion:
Our findings reveal novel pericytic miR-15a/16-1 mediated angiogenic targets in ischemic stroke.
Abstract TMP114: The Role of Iron Mediated Oxidative Stress and Lipid Peroxidation in the Development of Intracranial Aneurysm Rupture
Authors: Kamio Yoshinobu , Yamasaki Tomohiro , Kawakatsu Toru , Hashimoto Tomoki , Kurozumi Kazuhiko
Published: February 2024

Introduction:
Iron is an essential element for vascular wall maintenance. However, iron deposition in the vascular wall may cause oxidative stress, which can attack DNA, proteins, and lipid membranes via the Fenton/Haber-Weiss reaction. Iron-induced oxidative stress triggers lipid oxidation, inflammation, endothelial cell activation and intracranial aneurysmal formation, growth, and rupture. Subarachnoid hemorrhage from intracranial aneurysm rupture results in significant morbidity and mortality. This study used a mouse model of intracranial aneurysm to evaluate the effect of dietary iron restriction on aneurysm formation and rupture.

Methods:
Intracranial aneurysms were induced using deoxycorticosterone acetate-salt-induced hypertension and a single injection of elastase into the cerebrospinal fluid of the basal cistern. Mice were fed an iron-restricted diet or a normal diet. Aneurysm rupture was detected by neurological symptoms, while the presence of intracranial aneurysm with subarachnoid hemorrhage was confirmed by post-mortem examination.

Results:
The aneurysmal rupture rate was significantly lower in iron-restricted diet mice (37%) compared with normal diet mice (76%;
p
< 0.05). Serum oxidative stress, iron accumulation, macrophage infiltration, and 8-hydroxy-2′-deoxyguanosine in the vascular wall were lower in iron-restricted diet mice (
p
< 0.01). The areas of iron positivity were similar to the areas of CD68 positivity and 8-hydroxy-2′-deoxyguanosine in both normal diet and iron-restricted diet mice aneurysms.

Conclusions:
Compared with a normal diet, an iron-restricted diet reduced the incidence of intracranial aneurysmal rupture in mice via inhibition of iron accumulation in the aneurysmal wall. Iron may be a potential therapeutic target to prevent intracranial aneurysm rupture. Long-term iron restriction may be required to affect aneurysm formationrupture.
Abstract TMP15: Rurality is Associated With Negative Social Determinants of Health and Worse Acute Stroke Metrics, for Patients With Large Vessel Occlusion
Authors: Jagolino-Cole Amanda L , Dongarwar Deepa , Aroor Sushanth , Sheth Sunil , Asif Kaiz S , Yavagal Dileep R
Published: February 2024

Introduction:
One-fifth of the US population reside in rural areas (RAs). Large vessel occlusion (LVO), a quarter of ischemic strokes, portends poor outcomes. Only select hospitals have mechanical thrombectomy (MT) capability, worsening stroke care access in under-resourced areas.

Methods:
With an integrated Get With the Guidelines and Institute for Health Metrics and Evaluation registry (2016-2019), we compared demographics, acute stroke metrics, and social determinants of health (SDH) for patients with LVO stroke residing in RAs to those residing in nonrural areas (NRAs). Rural-urban commuting area codes determined rurality. We used Pearson’s chi-squared test for categorical variables, and Student’s t-test for continuous variables.

Results:
Of 145,554 patients with LVO, 3% resided in RAs. Of 46,629 patients post-MT, 3% resided in RAs. Patients with LVO residing in RAs were less likely of female gender, Hispanic ethnicity, and more likely of White or Native-Hawaiian/Pacific-Islander race, than patients residing in NRAs (Table 1). They were more likely insured by Medicare, less by Medicaid, and less likely baseline ambulatory, have a Bachelor’s degree, or own a home, with lower median income. Patients with LVO residing in RAs more likely transferred into hospitals from other facilities than arrived from scene, less likely received thrombolysis, and had higher onset-to-arrival time. Door-to-needle time (DTNT) was lower for patients with LVO residing in RAs, but comparable specifically for patients undergoing MT (median (IQR) 38 (25) vs 35 (23), p=0.09), compared to patients residing in NRAs.

Conclusions:
Patients residing in RAs comprised a small portion of patients with LVO in the integrated registry, and differed demographically to patients residing in NRAs. Rurality was associated with negative SDH and worse acute stroke metrics, except DTNT for patients post-MT. Understanding rural stroke disparities may identify approaches to equity for patients with LVO.
Abstract TMP27: Structural Network Dysfunction and Aberrant Structural-Functional Connectivity Coupling Correlate With Central Post-Stroke Pain of Thalamic Origin
Authors: Ye Chen , Wu Bo
Published: February 2024

Introduction and Hypothesis:
As the most frequent subtype of central post-stroke pain (CPSP), CPSP of thalamic origin can often be refractory to treatments and affect long-term prognosis of thalamic-stroke patients, while the mechanism remains unclear. We assumed that post-thalamic stroke CPSP might be a brain network disorder and aimed to investigate brain network alterations in post-thalamic stroke CPSP patients and explore whether these changes underlie clinical symptoms.

Methods:
A total of 92 participants were finally enrolled, of whom 62 were chronic thalamic stroke patients (26 had CPSP) and 30 were healthy controls. Using graph theory approaches, we compared the structural and functional brain network topological characteristics and structural-functional connectivity (SC-FC) couplings at multi-modular levels among the groups, and further explored their potential relationships with pain severity.

Results:
Distinct SC topological changes were found in CPSP patients, characterized as a higher clustering coefficient (Cp), global efficiency (Eg), local efficiency (Eloc), and lower characteristic path length (Lp) and normalized characteristic path length (Lambda) values than that in non-CPSP group. No significant differences were found in the FC network among the three groups. CPSP patients had significantly lower SC-FC couplings at the global and the structural Hub-modular levels. Further, we found significant and various correlations between pain severity and structural Lp, Eloc, global and Hub-modular SC-FC couplings.

Results:
These results indicated that thalamic stroke-induced distinct structural network dysfunction and SC-FC decoupling may be a novel neural mechanism for CPSP. It may provide new insights for future targeted neuromodulation therapies and individualized rehabilitative strategies in CPSP patients.
Abstract TMP37: Improved Outcomes for Acute Ischemic Stroke Patients After Implementation of the RapidAI Platform in a Comprehensive Stroke Center in Santiago, Chile
Authors: Lavados Pablo , Gonzalez Pablo , Olavarría Verónica , Albers Gregory W
Published: February 2024

Introduction:
In Latin America (LATAM), the prevalence of stroke is alarmingly high. The advancement of artificial intelligence (AI) technologies has potential to dramatically improve healthcare outcomes. RapidAI is a software solution that utilizes AI to quickly analyze imaging data to identify vascular occlusions and salvageable tissue. Physicians receive notifications and can review source images on the Rapid mobile app (RMA).

Methods:
This was a retrospective analysis of 1,672 consecutive acute stroke patients (AIS) treated at Clinica Alemana de Santiago between 2014-2023. Primary outcomes were the number of AIS patients treated with thrombolysis (IV tPA), mechanical thrombectomy (MT), or decompressive craniectomies as well as time to treatment. Secondary outcomes included discharge Modified Rankin score (mRS) and hospital length of stay (LOS).

Results:
This analysis included 824 patients pre-RapidAI installation and 848 after installation of Rapid CTP with hypodensity, CTA, ASPECTS, LVO and RMA communication. The baseline NIHSS and last know well to hospital arrival was balanced between the 2 study cohorts. Median time to IV tPA improved by 42 minutes (80 to 38 minutes, p < 0.0001). IV tPA utilization increased from 23% to 30% post-Rapid (p = 0.0033). MT procedure utilization increased from 5% pre-Rapid to 10% (p < 0.0001). Decompressive craniectomies were reduced from 13 to 4, LOS was unchanged. There was a favorable shift in the distribution of mRS scores at discharge in post-Rapid patients (p = 0.031) and a significant increase in mRS 0-1 outcomes (61% vs 45%).

Discussion:
Following implementation of the AI software platform in a comprehensive stroke center like Clinica Alemana, there was a significant increase in patients treated with IV tPA, faster door to tPA and/or MT times, a decrease in the number of DCTs, and improved discharge mRS scores. This work supports future studies expanding the use of AI technology for improving stroke outcomes in LATAM.
Abstract TMP4: Computational Fluid Dynamics Analysis Offers Novel Preoperative Insights for Unruptured Cerebral Aneurysms - Predicting Aneurysm Wall Thinning and Thickening -
Authors: Mori Tatsuya , Kimura Hidehito , Hayashi Kosuke , Kohmura Eiji , Sasayama Takashi
Published: February 2024

Objective:
The preoperative identification of thin-walled regions (TIWRs) and thick-walled regions (TKWRs) in cerebral aneurysms can contribute to enhancing surgical safety. Our recent computational fluid dynamics (CFD) analysis of cerebral aneurysms has demonstrated that the wall shear stress vector cycle variation (WSSVV) and the oscillatory shear index (OSI) can potentially predict TIWRs and TKWRs. This study aims to validate the accuracy of using WSSVV and the OSI to identify these areas and to report on their effectiveness in actual surgeries.

Methods:
Our cohort comprised 42 patients who underwent cerebral aneurysm clipping surgery at our hospital from January 2019 to September 2022. CFD analysis was performed using Hemoscope. We defined suspected TIWRs as blue regions and suspected TKWRs as red regions on both color maps. We evaluated the positive predictive value (PPV) by comparing these preoperative suspected areas with actual thin and thick areas determined intraoperatively under surgical microscopic observation.

Results:
Of the 42 patients, 15 were male and 27 were female. The average age was 63 years, and the average aneurysm size was 5.9 mm. The location of the aneurysms was the middle cerebral artery in 18 cases, the internal carotid artery in 15 cases, the anterior communicating artery in 8 cases, and the basilar artery in 1 case. WSSVV yielded a PPV of 83% for TIWRs and a PPV of 78% for TKWRs. In comparison, the OSI demonstrated a PPV of 77% for TIWRs and 76% for TKWRs. Spearman's rank correlation analysis revealed a strong correlation between WSSVV and the OSI; the correlation coefficient was 0.883 (p-value < 0.001).

Conclusions:
CFD analysis of unruptured cerebral aneurysms could be used to predict TIWRs and TKWRs using both WSSVV and the OSI with an accuracy of approximately 80%. The preoperative evaluation of the wall condition using CFD analysis appears to be highly reliable and is likely to contribute to the safety of cerebral aneurysm surgery.
Abstract TMP47: Identifying and Categorizing Delays to Endovascular Treatment in Patients With Large Vessel Occlusions
Authors: Padalia Arjun J , Harris Abigail L , Greever Matthew , Heitsch Laura , Panagos Peter D , Eby Brendan , Chatterjee Arindam R , Laurido-Soto Osvaldo J
Published: February 2024

Introduction:
Early endovascular treatment (EVT) in patients with large vessel occlusions (LVO) is associated with better outcomes. Identifying and categorizing delays to EVT may reveal areas for improvement.

Methods:
We prospectively identified all patients who underwent EVT at our hospital between May 2022 - 2023. We determined eight steps in acute care: arrival, imaging, IR activation, ED release, arrival to IR, groin puncture, first pass, and recanalization. We classified patients as delayed if any interval exceeded their rolling six-month median. We created 12 categories and 36 subcategories of delays. We used t-test and odds ratios to compare intervals and outcomes between delayed and non-delayed patients. We analyzed subgroups based on causes of delay and location of presentation.

Results:
Out of 183 LVO patients who underwent EVT, 111 (61%) were delayed. There were no significant differences in age, gender, last known normal to arrival, NIHSS, thrombolytic use, or TICI scale. The delayed group had higher door to groin (99 min), door to device (126 min), and door to recanalization (159 min) compared to the non-delayed group (40, 65, 81 min; p < 0.001). The most common causes of delay were: general case complexity (20%), which was associated with higher door to imaging (59 min, p < 0.001) and imaging to IR activation (37 min, p = 0.03); after hours presentation (19%), which was associated with higher door to imaging (53 min, p = 0.02) and imaging to IR activation (36 min, p = 0.01); and procedural complexity (18%) which was associated with higher groin to device (34 min, p < 0.001) and device to recanalization (53 min, p < 0.001) when compared to other causes of delay. Between the delayed and non-delayed group, there was no significant difference in the length of stay, change in NIHSS at discharge, in-hospital mortality, disposition, or 90-day mRS. Subgroup analysis showed a trend towards higher mortality in delayed patients who presented after hours (OR 3.60 (CI) 0.92-14.10) or in-hospital (OR 2.41 (CI) 0.57-10.19).

Conclusions:
We determined seven intervals where delays can occur between arrival and recanalization of LVO patients. We created a system for categorizing delays that showed areas for improvement including after hours and in-hospital stroke evaluation.
Abstract TMP48: Long-Term Cardiac Monitoring in Cryptogenic Stroke: The San Diego Experience
Authors: Davila Claire H , Meyer Dawn M , Hull Stephanie , Yoakum Stephanie , Bu Julia , Wood Carla N , Hansra Harjot , Hsu Jonathan C , Modir Royya F
Published: February 2024

Purpose:
Approximately 30% of all ischemic stroke (AIS) etiology is identified as cryptogenic. Implantable cardiac monitors (ICM) have become increasingly utilized based on results of the CRYSTAL-AF trial. Furthermore, this is now supported by current AHA guidelines. The purpose of this study was to assess the real-world reliability and experience of ICM in two large, academic Comprehensive Stroke Centers (CSC).

Methods:
We performed a retrospective review of prospectively collected data in two large, academic CSCs (UCSD Hillcrest Medical Center and UCSD Jacobs Medical Center/Sulpizio Cardiovascular Center). Patients were included if they had an AIS with cryptogenic etiology and had ICM placement between June 2017 and September 2023. Baseline demographics and ICM metrics were compared between patients that did or did not have atrial fibrillation (AF) detected with frequencies, chi-squared or t-test as appropriate.

Results:
A total of 134 patients were included (mean [SD]): age 69.1 years [12.5], female 40%, and median NIHSS 3 [SD 5]. AF was detected in 23.3%. Mean time to detection was 9.5 months (SD 12.8). The rate of detection was 13.5%, 18% and 21% at 6, 12, and 36 months since ICM implantation, respectively. Patients with AF were older at implantation (p=0.01) and had longer duration of monitoring (p<0.001). There was a significant difference in the number of ICM between sites (p=0.01). Males (p=0.01) and patients of white race were significantly more likely to have ICM. Despite this disparity, there was no significant difference in AF detection between sites (p=0.91), race/ethnicity (p= 0.12), or identified gender (p=0.43).

Conclusions:
Long-term cardiac monitoring has been shown to detect significant rates of AF, especially in cryptogenic stroke. Despite the small sample, this study found that over 20% of patients with cryptogenic stroke had AF. Examination of this population revealed disparities in implementation and placement pathways. More studies and process improvements are needed to identify and reduce disparities in this treatment-changing intervention.
Abstract TMP50: Deep Learning for Hyperdense Middle Cerebral Artery Detection Using High Resolution CT
Authors: Fussell David , Refugio Scott , Tang Cynthia Crystal , Chang Peter D
Published: February 2024

Introduction:
While CT angiography (CTA) remains the gold-standard for non-invasive diagnosis of large-vessel occlusion (LVO), accurate identification of potential thrombectomy patients on non-contrast CT (NCCT) has many practical workflow benefits. However, current evidence suggests that the hyperdense MCA sign on NCCT is an insensitive marker of LVO. In this study, we hypothesize that high-resolution NCCT (HR-NCCT) greatly increases the sensitivity of the hyperdense MCA sign and that a deep learning model can successfully identify the majority of LVO patients on HR-NCCT.

Methods:
A retrospective cohort of LVO and non-LVO patients with HR-NCCT (0.5-1.0 mm slice thickness) and CTA imaging was identified. For each patient, the location of a hyperdense MCA was annotated by an expert board-certified neuroradiologist after cross-referencing both HR-NCCT and CTA data. A convolutional neural network (CNN) was developed for localization of hyperdense MCA from HR-NCCT imaging only. In brief, the CNN is a 3D contracting-expanding network (18 layers; 596,364 trainable parameters) optimized with deep supervision and class weights. All model statistics are reported after aggregating results from a five-fold cross-validation.

Results:
A total of 97 LVO-positive and 110 LVO-negative cases were identified. Of the LVO cases, 81.4% (79/97) contained a hyperdense MCA upon expert review. Using these 79 positive (visible dense MCA) and 110 negative cases for training, the model demonstrated an overall 90.0% accuracy in hyperdense MCA detection (92.9% sensitivity, 88.2% specificity). Overall sensitivity was similar for M1 (91.7%) and M2-M3 (94.7%) occlusions. Additionally, of the 18 LVO cases labeled without a hyperdense MCA by expert review, 5 cases were identified correctly by the model and visually confirmed to match occlusion location on CTA.

Conclusion:
A deep learning model can identify 80.4% of all CTA-confirmed LVO patients using only HR-NCCT, with sensitivity approaching human experts. Combined with ASPECTS evaluation, NCCT-based imaging triage alone may be sufficient to identify the majority of candidate thrombectomy patients.
Abstract TMP8: Varicella Zoster Virus Infection in Children With Arterial Ischemic Stroke: The Chicken or the Egg?
Authors: Fullerton Heather J , Wintermark Max , Hills Nancy K , Amlie-Lefond Catherine , Bernard Timothy J , Dowling Michael M , Friedman Neil , Jordan Lori C , Grose Charles F ,   and the VIPS II Investigators
Published: February 2024

Introduction:
Serologic evidence of varicella zoster virus (VZV) infection has been associated with childhood arterial ischemic stroke (AIS). Questions of causality persist: does VZV infection cause AIS, or does AIS reactivate VZV? The Vascular effects of Infection in Pediatric Stroke (VIPS II) study aimed to examine this relationship.

Methods:
This North American 22-center prospective cohort study enrolled 205 children (28 days-18 years) with AIS (2017-2022). Blood samples were hyperacute (≤72hrs; n=194), acute (4-7 days; n=180) and convalescent (1-6 weeks; n=73). A virology research lab used ELISA to measure VZV IgM and IgG titers. A pediatric virologist (CG) interpreted the results and classified the evidence of infection. Low-level IgG seropositivity is consistent with prior vaccination/infection. Highly elevated IgM in hyperacute/acute samples indicated

reactivation
coincident with
stroke

. Rising IgG titers between hyperacute and convalescent samples, occasionally with a high IgM in convalescent sample, indicated

reactivation
after
the stroke

.

Results:
Median age (IQR) was 11.6 years (5.3, 15.6). All 205 cases were low-level IgG positive; 160 (78%) reported prior VZV vaccination and 3 reported remote chicken pox. Serologies for 15 (7.3%; 95% CI 4.1, 11.8%) indicated VZV reactivation coincident with stroke; prior VZV vaccination reported in 14 and unknown in one. Stroke etiology amongst these 15 was definite arteriopathy in 4 (27%), possible arteriopathy in 4 (27%), cardioembolic in 5 (33%), and idiopathic in 2 (13%) (compared to 37%, 37%, 10%, 14%, respectively, for the other 190). Among 73 with convalescent samples, 17 (23%) had VZV reactivation after stroke. All cases of VZV reactivation were asymptomatic
zoster sine herpete
(herpes zoster without rash).

Conclusions:
While stroke triggered VZV reactivation in 23% of cases, 7.3% had evidence of
zoster sine herpete
at the time of their stroke, implying a causal role. We could not distinguish antibodies to vaccine virus versus wild-type; these zoster cases could represent reactivation of vaccine virus or a break-through wild-type varicella infection. Either scenario would be unexpected in this current era of routine childhood VZV vaccination and low rates of pediatric chicken pox or zoster.
Abstract TMP84: Multi-Institutional Validation of an Automated Segmentation Tool for Intracerebral Hemorrhage (ICH) and Peri-Hematomal Edema (PHE) on Head CT
Authors: TRAN ANH TUAN , Desser Dmitriy , Abou Karam Gaby , Zeevi Tal , Qureshi Adnan I , Werring David J , Malhotra Ajay , Falcone Guido J , Sheth Kevin N , Nawabi Jawed , Payabvash Seyedmehdi
Published: February 2024

Objective:
In patients with acute intracerebral hemorrhage (ICH), the volume of hemorrhage, and perihematomal edema (PHE) are representative of primary, and secondary brain injury, respectively. Automated quantification of ICH and PHE volumes from admission non-contrast head CT can facilitate evaluation of large stroke datasets, and expedite treatment triage when volume cutoffs are applied. We aimed to train and externally validate an automated model for segmentation and quantification of ICH and PHE volumes on non-contrast head CT scans.

Methods:
For training of the model, we used the data from multicentric ATACH-2 clinical trial with head CTs from eleven medical institutes in six countries. The model was then exported and tested on two external datasets from Yale and University of Berlin. We designed an automated pipeline for extracting brain window from 3D non-contrast head CT, skull stripping, resampling to homogenous voxel size, and segmentation. For segmentation we applied a deep learning model based on 3D full resolution nnUNet. We used the Dice Similarity Coefficient (DSC), Hausdorff Distance (HD), and Volume Similarity (VS) between automated segmentation and ground truth manual segmentation volumes to evaluate the models’ performance.

Results:
A total of 854 patients from the ATACH-2 trial (854 х2, baseline and follow-up CT scans) were used for training of the model in 5-fold cross-validation. In validation folds, the model achieved a mean DSC=0.90±0.10, HD =1.42±16.0mm, and VS=0.95±0.10 for ICH; and DSC=0.74±0.12, HD =3.0±16.5 mm, and VS=0.91±0.12 for PHE. In the externaltesting cohort from Yale (200 patients х2, baseline and follow-up CT scans), the model archieved median DSC=0.93, HD=0.98 mm, and VS=0.97 for ICH; and median DSC=0.69, HD=4.52 mm, and VS=0.84 for PHE. In the externaltesting cohort from Charité Hospital, University of Berlin (915 baseline CT scans), the model archived median DSC=0.87, HD=4 mm, and VS=0.90 for ICH; and median DSC=0.65, HD=5 mm, VS=0.85 for PHE.

Conclusion:
We trained, validated, and externally tested an end-to-end automated tool for segmentation of both ICH and PHE on non-contrast head CT. Such tool can facilitate treatment triage for trials when volume cutoffs are applied for enrollment.