bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP215: Endovascular and Medical Management Strategies for Caroticocavernous Fistulae: A Single Center Retrospective Safety and Efficacy Analysis
Authors: Vranic Justin , Regenhardt Robert , Awad Amine , Doron Omer , Rabinov James
Published: February 2024

Background:
Caroticocavernous fistulae (CCF) are a rare subtype of intracranial arteriovenous fistulae with variable clinical and angiographic presentations. This study aimed to describe the clinical outcomes in a cohort of CCF patients and identify clinical and angiographic features differentiating patients more likely to benefit from endovascular intervention.

Methods:
A single-center, retrospective analysis was performed to identify all patients with angiographically-confirmed CCF between 2000 and 2022. Pertinent data, including clinical symptoms, angiographic findings, treatment strategies, recurrence rates, and complications, was collected.

Results:
A total of 84 patients were included, of whom 67 (80%) underwent endovascular intervention and 17 (20%) were conservatively managed. Primary endovascular techniques were transvenous coil embolization (78%), feeder artery embolization (16%), and ICA flow diversion (8%). High-risk clinical symptoms, such as reduced visual acuity, and angiographic features, such as cortical and ophthalmic venous reflux, were more common in the intervention group (p<0.05). All direct (Barrow Type A) CCFs underwent endovascular intervention (32% vs 0%, p=0.005), while indirect (Barrow types B-D) CCFs were common in the conservatively managed group (100% vs 68%, p=0.005). 31% of treated CCFs required retreatment, which primarily occurred with Barrow type D CCFs and following transvenous coil embolization. Procedure-related complications occurred in 10% of cases and consisted of cranial nerve palsies (n=5), asymptomatic intracranial dissection (n=1), and asymptomatic distal thromboembolic occlusion (n=1).

Conclusion:
High-risk symptoms and angiographic features favor endovascular intervention. Various embolization techniques, including transvenous coil embolization, proved safe and effective. In select CCF patients without high-risk clinical or angiographic features, conservative observation is a safe and effective alternative to endovascular embolization. Complications were rare, and most were transient, emphasizing the safety of endovascular management. Longitudinal angiographic surveillance is essential for monitoring fistula persistence or recurrence.
Abstract TP22: Delirium, Infection, and Risk of Dementia in Patients With and Without Cerebral Small Vessel Disease
Authors: Luengo-Fernandez Ramon , Pendlebury Sarah , Downer Matthew , Rothwell Peter
Published: February 2024

Background:
The increased risk of dementia after delirium and infection might be influenced by cerebral small vessel disease-SVD. We determined associations between hospitalisations with delirium, and with infection on follow-up after TIA/minor stroke and 5-year dementia risk, stratified by moderate/severe SVD on baseline brain imaging.

Methods:
In a population-based study (n=94 567) of TIA/minor stroke (NIHSS<3) ascertained 2002-2012 (Oxford Vascular Study-OXVASC), hospitalisations on follow-up were identified from the Oxford Cognitive Comorbidity, Frailty and Ageing Research Database-ORCHARD. Delirium and infection were defined by ICD-10 coding supplemented by hand-searching of hospital records. Dementia was diagnosed using clinical/cognitive assessment, medical records and death certificates. Dementia risk was determined using time-varying Cox analysis with multivariable adjustment.

Findings:
Among 1,369 patients (n=655 TIA, n=714 minor stroke, mean/SD age=72/13 years, 674 female, 364 moderate/severe SVD), 209 (15%) developed dementia. Hospitalisation during follow-up occurred in 891 (65%) patients of whom 103 (12%) had ≥1 delirium episode and 236 (26%) had ≥1 infection episode. Hospitalisation without delirium/infection did not predict subsequent dementia (HR=1.01,95%CI:0.86-1.20). In contrast, hospitalisation with delirium predicted subsequent dementia independently of infection in patients with and without SVD (HR=2.64,1.47-4.74 vs. 3.41,1.91-6.09, both p<0.001) especially in those with normal baseline cognition (HR=4.01,2.23-7.19 vs 3.94,1.95-7.93,both p<0.001). However, hospitalisation with infection only predicted dementia in those with moderate/severe SVD (HR=1.75,1.04-2.94 vs 0.68,0.39-1.20,p
diff
=0.023).

Interpretation:
The increased risk of dementia after delirium is unrelated to the presence of SVD, whereas infection increases risk only in patients with SVD, suggesting differences in underlying mechanisms and in potential preventive strategies.
Abstract TP226: Analysis of the Association Between Lipoprotein(a) Levels and Carotid Plaque and Coronary Artery Calcium Using Health Checkup Data
Authors: Sung Minsoo , Lee Kyung-Yul , Jung Yo Han
Published: February 2024

Background:
Lipoprotein a (Lp(a)) is known to be associated with coronary artery disease and carotid artery atherosclerosis. We analyzed the association between Lp(a) levels, coronary artery calcium score (CACS), and carotid plaque using data from individuals undergoing health check-ups.

Methods:
We enrolled patients who underwent all Lp(a) measurements, coronary artery calcium score computed tomography(CT), and carotid ultrasound at Gangnam Severance Hospital from January 2017 to December 2022. Lp(a) levels were categorized into two groups: below 50 mg/dl and 50 mg/dl or higher. Carotid ultrasound results were divided into two groups based on the presence or absence of plaque. Coronary artery calcium score CT results were analyzed in two groups: CACS=0 and CACS>0.

Results:
A total of 2620 subjects were enrolled. 1692 (64.6%) were male. Mean age was 57 years. Lp(a) levels of 50 or higher were found in 177 (6.8%) subjects. Carotid plaque was observed in 1140 (43.5%) subjects and CACS>0 in 1172 (44.7%) subjects. Multivariable logistic regression analysis was performed. There was an association between Lp(a) 50mg/dl or higher and carotid plaque (unadjusted odds ratio = 1.406, confidence interval = 1.036 - 1.908) (adjusted odds ratio = 1.383, confidence interval = 1.010 - 1.894). An association was also found between Lp(a) 50mg/dl or higher and CACS>0 (unadjusted odds ratio = 1.400, confidence interval = 1.031 - 1.900) (adjusted odds ratio = 1.378, confidence interval = 1.002 - 1.895). Carotid plaque and CACS>0 were associated (unadjusted odds ratio = 4.393, confidence interval = 3.725 - 5.182) (adjusted odds ratio = 2.380, confidence interval = 1.970 - 2.876).

Conclusions:
This study demonstrates that individuals with Lp(a) levels of 50 mg/dl or higher are at increased risk for carotid plaque and CACS. This association remains independent even after adjustment for factors such as statin use or low-density lipoprotein cholesterol (LDL-C) levels. Therefore, increased attention to the occurrence and progression of coronary artery disease and carotid artery atherosclerosis is necessary in individuals with Lp(a) levels of 50 mg/dl or higher, even if LDL-C levels are well controlled.
Abstract TP229: Stroke Rate and Associated Factors in Individuals With Primary Brain Gliomas and Brain Radiation Therapy: A Retrospective Cohort Study
Authors: Ryan Dylan , Sugita Megumi , Lipp Eric , Peters Katherine , El Husseini Nada
Published: February 2024

Background/Objectives:
The risk of stroke in individuals with brain gliomas may be increased due to several possible factors including chemotherapy, radiation-induced toxicity, and concomitant vascular risks. We report on the stroke rate and associated factors following brain tumor diagnosis and radiation therapy.

Design:
This is a retrospective cohort study, from a single tertiary academic brain tumor center, of patients with brain gliomas diagnosed between 2004-2021 who received brain radiation therapy during their treatment. Chi-square test was used to calculate the odds ratios.

Results:
Among a total of 912 patients with primary gliomas who received radiation therapy, stroke subsequently occurred in 93 patients (10.2%). Strokes were ischemic in 72.0% (N=67), intracerebral hemorrhage (ICH) in 25.8% (N=24), and subarachnoid hemorrhage in 2.2% (N=2). Individuals who sustained a stroke were 44.1% female and had a mean age of 54.2 years (range 21-84) at the time of stroke diagnosis. Of those who had a stroke, 64.5% (N=60) were also taking bevacizumab at the time of stroke. Median time from initiation of radiation therapy to stroke was 653 days (range 0-3788). Median radiation dose was 5940 cGy (range 1800-6000). The following factors were associated with a higher odd of having a stroke: radiation necrosis (OR 4.51; 95% CI 1.98-10.29, P=0.0003); hypertension (OR 1.82; 95% CI 1.17-2.82, P=0.008); hyperlipidemia (OR 5.50; 95% CI 3.45-8.78, P<0.0001); and diabetes (OR 2.19; 95% CI 1.25-3.84, P=0.007). Among stroke patients, 80.6% had strokes on the same side as radiation therapy. Those who were taking bevacizumab were more likely to have an ICH (31.7% vs. 15.1%, OR 2.60, 95% CI 0.87-7.77, P=0.09) as compared to other stroke types.

Conclusions:
Individuals with primary brain gliomas undergoing radiation therapy who were subsequently diagnosed with a stroke had higher rates of comorbid vascular risk factors and radiation necrosis.
Abstract TP230: Atrial Fibrillation and Short-Term Outcomes After Cancer-Related Ischemic Stroke
Authors: Wahbeh Farah , Zhang Cenai , Beyeler Morin , Kaiser Jed , Liao Vanessa , Pawar Anokhi , Parikh Neal S , Kamel Hooman , Navi Babak B
Published: February 2024

Introduction:
Atrial fibrillation (AF) and cancer are both independently associated with worse outcomes in patients with acute ischemic stroke. Few studies have evaluated the impact of AF on outcomes of cancer-related stroke. We aimed to determine if AF is associated with worse short-term outcomes in patients with stroke and comorbid cancer.

Methods:
Using the 2016-2019 National Inpatient Sample, we identified all hospitalizations with diagnosis codes for cancer and ischemic stroke. The primary exposure was a diagnosis of AF. The primary outcome was in-hospital mortality. The secondary outcomes were length-of-stay and discharge other than to home. We used multivariable logistic and linear regression models, as appropriate, adjusted for age, gender, race-ethnicity, and the Charlson Comorbidity Index, to examine the association between AF and study outcomes.

Results:
Among 150,200 hospitalizations with diagnoses of cancer and ischemic stroke (mean age 72 years, 53% male), 40,084 (26.7%) included comorbid AF. Compared to hospitalizations without AF, hospitalizations with AF had higher rates of in-hospital mortality (14.8% vs 12.1%, p<0.001) and non-home discharge disposition (83.5% vs 75.1%, p<0.001) as well as longer mean length-of-stay (8.4 days vs 8.2 days, p<0.001). In multivariable analyses, AF remained independently associated with higher odds of in-hospital mortality (adjusted OR, 1.34; 95% CI, 1.24-1.46), non-home discharge disposition (adjusted OR, 1.32; 95% CI, 1.23-1.42), and longer length-of-stay (adjusted mean difference, 13.7%; 95% CI, 10.9%-16.7%).

Conclusions:
In cancer-related ischemic stroke, comorbid AF is associated with worse short-term outcomes, including higher odds for in-hospital mortality, worse discharge disposition, and longer hospital stays.
Abstract TP236: Racial Disparities in Young Patients With Ischemic Stroke in Central Connecticut
Authors: Akram Nida , Li Ya-Huei , Nouh Amre M , Hou Yan
Published: February 2024

Introduction:
A rising prevalence of stroke in young patients was noticed in recent years. Studies have reported racial disparities in young stroke patients and less desired outcomes of minorities. The healthcare system located in central Connecticut provides stroke care for diverse populations allowing investigations of racial disparities in young stroke population. This study aimed to identify potentially modifiable factors for better stroke treatment and prevention in minority populations.

Methods:
We retrospectively identified young patients (aged 18-55 years) who were admitted with ischemic stroke from 01/2014 to 12/2022. Race groups were characterized as non-Hispanic White (White), non-Hispanic Black (Black), and Hispanic. Socioeconomic status, risk factors, stroke etiology, acute interventions and short-term outcomes were accessed. Comparisons among racial groups were tested with Chi-square and Wilcoxon rank sum tests as appropriate.

Results:
A total of 915 patients were identified, the median age was 49, 58.8% were male, and 60.4% White, 21.6% Black, 17.9% Hispanic. White lived in households with a higher median income than Hispanic and Black (p<0.001). Compared to White, black and Hispanic had higher rate of Diabetes, Hypertension and prior stroke (p<0.001). The rates of other risk factors (hyperlipidemia, smoking, illicit drug use, chronic heart failure, coronary artery disease, and atrial fibrillation) did not vary by race. The rates of stroke etiologies (large vessel disease, cardioembolic stroke, cryptogenic stroke and other determined etiology) were similar among racial groups, yet the trend showed a higher rate of dissection stroke in White (White 7.9 % vs. Black 3.9% and Hispanic 3.8%) and a higher rate of small vessel disease stroke in Black and Hispanic (White 7.9 % vs. Black 17.3% vs. Hispanic 12.4%). Acute intervention (IV tPA, thrombectomy) and short-term outcomes (mRS and disposition at discharge) were similar among groups.

Conclusions:
This study highlighted a higher prevalence of hypertension and diabetes may correlate with a high rate of small vessel disease in Black and Hispanic young stroke patients. A tailored interventions of hypertension and diabetes for stroke prevention are urged in minorities.
Abstract TP247: Focused Approach to Tailor Native American Stroke Awareness Messaging in Montana
Authors: Guzman Joani , Brown Stefanie , Wintermeyer Jay , Burcham Heather
Published: February 2024

Overall, African Americans, Hispanics, and Native Americans have higher stroke risks, stroke occurrence at an earlier age, and for some people of color possibly more severe strokes than non-Hispanic whites. Native Americans make up approximately 6.5% of the population of Montana—equating to around 78,000 people. A focused objective of the Mission: Lifeline Stroke Montana initiative was to specifically engage with Native Americans through public awareness campaigns to improve stroke outcomes in Montana.

Method:
In 2021 a survey was deployed to Native Americans in Montana to evaluate knowledge, awareness, and understanding of stroke risk factors, signs and symptoms, and what to do in the event of a stroke. Surveys were collected from eight tribal nations. The results of this survey guided message development to create a tailored public awareness campaign.

Results:
Analysis of the 398 surveys collected showed a representative sampling of respondents by age, gender, education, and geographic area. The key findings were:· Less than 38% of respondents reported having ever talked with a healthcare provider about their risk of stroke, with men being less likely than women to have discussed their stroke risk.· Nearly 94% of respondents said they knew high blood pressure was a risk factor for stroke but have not discussed their personal risk with a healthcare provider.· When asked what action they would take in the event of a possible stroke, over 75% of respondents said they would call 911. Less than half of the respondents indicated the best mode of transportation, in the event of a possible stroke, was an ambulance.

Conclusion:
Based on survey findings, specific engagement strategies were centered around two main messages:-Know the risk factors for stroke and talk with a healthcare provider about your risk.

-Stroke is a medical emergency that requires immediate attention. Call 9-1-1 at the first sign of stroke to access treatment through Montana’s Stroke System of Care.

A post-campaign survey will be deployed in the fall of 2023. This survey will aim to assess the effectiveness of these tailored campaign initiatives.
Abstract TP253: Early Neurological Deterioration Following Small Subcortical Infarcts: A Systematic Review and Meta-Analysis
Authors: Goldstein Eric D , Muppa Jayachandra , Chahien Dalia , Shu Liqi , Yang Dixon , Gutierrez Jose , Furie Karen , Meschia James F , Yaghi Shadi
Published: February 2024

Background and Objectives:
Acute small subcortical infarcts (SSI) result in high rates of early neurological deterioration (END) despite best medical management. Those with SSI-related END have worse functional outcomes after stroke leading to increased morbidity. Presently, it is unknown in a robust manner the incidence or risk factors for END within this demographic. The aim of this study was to perform a systematic review and meta-analysis to understand the incidence and risk factors of SSI-related END.

Methods:
We searched PubMed, Cochrane Library, and Google Scholar between January 1, 2000, and June 1, 2022, including both retrospective cross-sectional and prospective observational studies. The primary outcome was development of END based on publishing authors’ definition. Abstracted data included age, sex, cohort size, diagnoses of hypertension, hyperlipidemia, diabetes mellitus, study definition of END and SSI, and presence of branch atheromatous disease (BAD) and lesion diameter.

Results:
We identified 31 studies enrolling 6376 patients. Most studies were conducted in East Asia (27/31, 87%) and had a least some concern for risk of bias. Funnel plot illustrated a high level of publication bias favoring high incidence studies. END was commonly defined as ≥ 2 overall NIHSS change or ≥ 1 motor change within 3 to 7 days from admission (average: 5 days). A pooled proportion of END was 22% (95%CI 0.19 - 0.25, I2 = 91.2%, 31 studies). Meta-regression identified that female sex [risk ratio (RR) 1.23, 95%CI 1.09-1.39, I2=30.8%, 31 studies], diabetes mellitus (RR 1.16 95%CI 1.01-1.33, I2=38.4%, 30 studies), and BAD (RR 1.99 95%CI 1.61-2.46, I2=50.7%, 17 studies) as risk factors for END.

Discussion:
Our data identified primarily within an East Asian cohort that risk factors for SSI-related END include diabetes mellitus and branch atheromatous disease with a pooled prevalence of END occurring in 1 in 4 patients. Future studies are needed to understand treatment and preventative strategies for this patient population.
Abstract TP255: Racism, Resilience, and Quality of Life in Black Stroke Survivors
Authors: Love Mary F , Okpala Munachi N , Cox Sonya , Brooks Andrea , Cooksey Gail , Beamon Emily , Sharrief Anjail Z
Published: February 2024

Introduction:
Stroke impairs stroke survivor (SS) quality of life (QoL). Black SS in the US also endure stress from structural, cultural, and interpersonal racism. Resilience is a dynamic process of maintaining stable functioning after an event such as stroke. This observational study aimed to assess the effects of racism and resilience on Black SS QoL.

Methods:
Participants were community-dwelling SS (age ≥ 18) who identified as African American or Black and experienced a stroke within 8 weeks. Baseline data collection included exposure (discrimination, vigilance, resilience), demographic, clinical, and psychosocial variables. Outcome data for QoL was gathered after 6 months. The effects of exposure variables and covariates on QoL were analyzed with multiple linear regression.

Results:
Participants (n=74) had a mean age of 56.2, 32% were in marital or partner relationships, and 58% were female. Most participants (84%) had ischemic stroke, with no more than mild disability (mRS 0-2 for 80%). Over half of participants had some college (32%) or a college degree (20%). The remaining 46% had a high school education or less. Work status included 32% currently working, 15% not working, 28% retired, and 24% disabled. Half reported an annual household income of < $25,000, with 63% living at ≤ 200% above the US poverty level. Participants reported moderate (64%) to high (8%) perceived stress, and 14% had moderate to moderately severe anxiety. Resilience was correlated with stress (r=-.59, p<.001) and anxiety (r=-.66, p<.01). At 6-month follow-up (n=44), QoL domains were very low for social relations (
M
=36.83, SD=17.76) and environment (
M=
35.04, SD=14.57), and moderately low for physical (
M
=46.49, SD=19.22) and psychological (
M
=54.39, SD=17.23). Higher vigilance and higher disability explained 23.3% of the variance in social relations QoL (F=7.545, p=.002). Higher resilience and higher socioeconomic status explained 25.7% of the variance in psychological QoL (F=5.524, p=.009).

Conclusions:
This sample had significant baseline socioeconomic disadvantage and increased psychosocial stress at baseline, and diminished QoL 6 months post-stroke. Future research with larger samples is warranted.
Abstract TP257: Atherogenic Dyslipidemia Advances Crucially the Aortic Complicated Lesion in Cryptogenic Stroke
Authors: Kikuno Muneaki , Ueno Yuji , Kanemaru Kodai , Takekawa Hidehiro , Shimizu Takahiro , Kuriki Ayako , Tateishi Yohei , Doijiri Ryosuke , Shimada Yoshiaki , Yamaguchi Eriko , Koga Masatoshi , Kamiya Yuki , Ihara Masafumi , Tsujino Akira , Hirata Koichi , Hasegawa Yasuhiro , Terashi Hiroo , Hattori Nobutaka , Urabe Takao
Published: February 2024

Background and purpose:
The aortic complicated lesion (ACL) is a notable embolic source of cryptogenic stroke (CS) observed in 10-60 % of patients. Although the antithrombotic and statin therapy are certainly effective, the recurrence of aortogenic stroke is not rare. Atherogenic dyslipidemia (AD) is regarded as the significant residual risk of cardiovascular diseases even under the statin remedy and characterized by low high-density lipoprotein (HDL) and high triglyceride (TG). In the present study, we aimed to clarify the underlying association between ACL and AD.

Methods:
Clinical data of CS patients admitted between April 2014 and December 2016 in Japanese 8 institutes and underwent transesophageal echocardiography (TEE) were analyzed in the present study. Low HDL was defined as ≤ 40 mg/dl and high TG was defined as ≥ 150 mg/dl in the fasting condition, respectively. Furthermore, AD must satisfy both cut-off values. Based on these criteria, patients were divided into 4 groups as AD group, HDL group, TG group, and non-AD group to compare the clinical features.

Results:
Of 664 CS patients, 68 (57 men, 68.6 ± 11.1 years) met the criteria of AD (AD group), and 108 (90 men, 68.5 ±13.7 years) fulfilled the low HDL only (HDL group), 115 (76 men, 66.9 ± 11.7 years) merely met the high TG (TG group), 373 (223 men, 69.4 ± 13.1 years) satisfied the neither (non-AD group). In a univariate analysis, ACL in arch revealed with TEE was significantly more frequent in AD group (55.9 vs 38.0 vs 39.1 vs 33.8 %, p=0.007). In a multiple regression analysis, male (OR 2.57, 95%CI 1.23-5.38, p=0.012), body mass index (unit OR 1.16, 95%CI 1.08-1.25, p<0.001), diabetes (OR 2.52, 95%CI 1.41-4.53, p=0.002), ACL in arch (OR 2.12, 95%CI 1.19-3.80, p=0.011) were independently, and past history of stroke (OR 0.35, 95%CI 0.14-0.90, p=0.030) was inversely associated with AD group.

Conclusions:
Although the previous study exhibited that AD was predominantly associated with intracranial stenosis in atherothrombotic brain infarction, AD was also crucially related to ACL in CS in the present study. Concerning the aortogenic stroke, more intensive and pleiotropic lipid-lowering therapy would be efficacious for further treatment.
Abstract TP263: Risk Factor Profile With Carotid Web in Young Stroke
Authors: Heshmati Keyvan , Patel Himanshu A , Ryan Kathleen A , Yarbrough Karen L , Mixon Lakeisha M , Williams Devin E , Kittner Steven J , Cronin Carolyn A
Published: February 2024

Introduction:
Carotid webs an increasingly recognized cause of first and recurrent stroke in the young. Carotid webs are non-atherosclerotic and non-inflammatory shelf-like intraluminal protrusions in the carotid bulb. There are relatively limited data on the race, sex, and risk factor profile of these patients.

Methods:
We conducted a retrospective review of stroke patients between the ages of 18 to 50 years presenting to our Young Stroke Center between April 2022 through August 2023. For each case, data including basic demographics and medical history were collected, and stroke etiology was determined by a vascular neurologist. Patients with carotid web as the stoke etiology were compared to all non-carotid web stroke etiologies with respect to baseline demographics and comorbidities including hypertension, dyslipidemia, diabetes, smoking, and obesity. Analysis was performed with logistic regression adjusting for age, sex, and race.

Results:
Of 179 patients in the registry, 9 patients had carotid web compared with 170 patients with non-carotid web as their stroke etiology. There were no significant differences in age at time of stroke (41.6 ± 5.5 vs. 38.5 ± 8.0 years). The carotid web group had a higher proportion of females, but this was not statistically significant (88.9% vs. 61.8% female, p=0.11). In the carotid web group, there were 8 Black and 1 non-Black Asian patients which was significantly different compared to the non-carotid web group (88.9% vs. 52.4% Black; p=0.03). A significantly larger proportion of patients with carotid web presented with no baseline cardiovascular risk factors (77.8% vs. 17.7%; OR [95% CI]: 35.7 [5.6-229]).

Conclusion:
In the young stroke population, strokes attributed to carotid webs occur independently of typical stroke comorbidities. Additionally, Black patients are disproportionately affected and there is a trend toward increased incidence of strokes due to carotid webs in women.
Abstract TP27: Transcriptional and Functional Characterization of Microglia in Vascular Dementia
Authors: Diaz Sebastian , Zhang Le , Askenase Michael , DeLong Jonathan , Sansing Lauren H
Published: February 2024

Introduction:
Proper function of the brain relies on sufficient blood supply to meet local energy demand. Age-related pathologies like cerebral small vessel disease (cSVD) compromise the ability of blood vessels to meet local energy demands and lead, over time, to the development of vascular dementia (VaD). Microglia are essential for maintaining homeostasis and have been shown to exacerbate inflammation and disease progression in neurodegenerative diseases. Activated microglia are present in the white matter lesions of human post-mortem VaD brains. However, their role in VaD progression is poorly understood.

Hypothesis:
Our main objective is to identify microglial pathways that contribute to VaD. We hypothesize microglial dysregulation interferes with brain homeostasis and wound healing, ultimately contributing to disease progression.

Methods:
Post-mortem samples of periventricular white matter from male and female elderly individuals exhibiting brain pathology consistent with VaD (n=4), along with age- and sex-matched controls without VaD (n=4) were acquired from the NIH NeuroBioBank. We performed single-nuclei RNA sequencing followed by differential gene expression analysis using Seurat and downstream analyses using Ingenuity Pathway Analysis.

Results:
Over 30,000 nuclei were analyzed. Transcriptomic results reveal profound differences in the microglial transcriptome in VaD, with 690 differentially regulated genes in microglia between cases and controls. Genes related to pathways such as complement production, phagocytosis, macrophage activation and overall protein production are downregulated in VaD while IL-10 production is upregulated (Figure 1B).

Conclusions:
Our data suggests microglia in VaD adopt a unique transcriptional signature, distinct from that observed in disease-associated microglia in other neurodegenerative conditions, which may impact their ability to maintain homeostasis in VaD.
Abstract TP272: Project Echo’s Beneficial Effect on Stroke Prevention Education for Healthcare Professionals
Authors: Qureshi Zain A , Boone-Sautter Kennedy , Ahmed Aiesha , Chakraborty Tia
Published: February 2024

Introduction/Background:
Project ECHO (Extension for Community Healthcare Outcomes) is a telehealth initiative that connects specialists with healthcare providers (HCPs) through videoconferencing, enabling knowledge-sharing and skill-building to improve preventative patient care in underserved areas This program was implemented in a study in Western Michigan concerning primary stroke prevention in vulnerable populations including women, African Americans, and Latinx patients.

Research Questions/Hypothesis:
We hypothesized that the program would effectively increase understanding among HCPs of effective risk-factor modifications in these populations.

Goals/Aims:
The study aimed to implement ECHO to increase access to stroke-preventative education for HCPs who serve vulnerable populations. These populations usually lack primary stroke prevention knowledge tailored to their individual risk factors.

Methods/Approach:
Cornwell Health conducted 5 didactic sessions with these goals in focus. We used participant surveys conducted before/after the program to assess the program’s efficacy. The curriculum focused on lifestyle modifications and covered 2013/2014 AHA stroke prevention guidelines and 2013 AHA/ACC guidelines to reduce cardiovascular risk.

Results/Data:
A 40% response rate was achieved from HCP participants. The average number of correct answers on the surveys out to 10 increased from 6 ± 1.2 questions on the pre-survey to 6.5 ± 1.0 on the post-survey. Confidence in counseling patients on risk-factor modification increased from 18.8% to 40.6%. Additionally, 87.5% of participants expressed interest in future Project ECHO programs on primary stroke prevention.

Conclusion:
The ECHO platform was beneficial concerning HCP understanding of risk-factor modifications in primary stroke prevention, confidence in counseling patients, and evaluation of the program’s educational value. The ECHO platform proved to be instrumental in reaching these outcomes and can be implemented in various capacities relating to community outreach and education.
Abstract TP281: Ischemic Stroke Risk in Transient Global Amnesia
Authors: Pyo Stella , Sangha Navdeep S , Taleb Shayandokht , Ajani Zahra , Gaffney Denise , Ly An , Cheng Pamela
Published: February 2024

Introduction:
There has been much debate on whether transient global amnesia (TGA) increases the risk for subsequent cerebrovascular events. This study aims to assess whether certain comorbidities may increase risk for a future ischemic event.

Methods:
We retrospectively identified patients within the Southern California KP region using ICD 9 and ICD-10 codes who had a diagnosis of TGA from 2012-2017. Patients with prior history of stroke or TIA were excluded. We then evaluated differences in baseline demographics and characteristics in patients who were admitted to the hospital with an ischemic stroke within five years compared to those who were not.

Results:
There were 136 patients diagnosed with TGA between 2012-2017. Of 136, 10 (7.4%) were admitted with an acute stroke. There were no differences in age, gender, or race/ethnicity between those who had a stroke versus those that did not. In terms of vascular risk factors, those who had history of coronary artery disease (CAD) or prior MI were more likely to have a stroke compared to those who did not {6 (60%) vs. 26 (20.8%), p = 0.005}. There were no differences in other risk factors.

Conclusion:
After the diagnosis of TGA, those who have a history of CAD or prior MI were more likely to have an ischemic stroke within five years.div>
Abstract TP282: Impact of Interhospital Transfer on Patients Undergoing Endovascular Thrombectomy for Acute Ischemic Stroke From a Comprehensive Stroke Center
Authors: Khan Hamza , Chaudhry Saqib A , Laleka Maham , Chaudhry Mohammad Rauf , Ali Akif , Fang Yun , Khan Ameerdad , Shuaib Ashfaq , Qureshi Adnan
Published: February 2024

Objective:
This study aims to evaluate how interhospital transfers impact the correlation between functional outcomes, mortality, reperfusion rates, and workflow time metrics in patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion (LVO).

Background:
This analysis is based on a prospective database encompassing consecutive patients who underwent EVT for LVO between January 2021 and June 2023 at a comprehensive stroke center (CSC).
Main Outcome Measures:
The primary outcome measures assessed include the rate of favorable 90-day functional outcomes (modified Rankin Scale 0-2), successful reperfusion (Thrombolysis in Cerebral Infarction scale grade 2b or 3), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. Additionally, essential workflow time metric milestones were analyzed.

Results:
Out of 363 patients, 172 (47.4%) were transferred from other hospitals. The transferred patients were relatively younger than those who presented directly (66.5 ± 15.6 vs. 70.6 ± 14.5). No significant differences were observed in baseline characteristics, including gender, National Institutes of Health Stroke Scale score, and the rate of intravenous thrombolysis, between the transferred and direct presentation groups (all p > 0.05). The time of symptom onset to groin puncture time was significantly higher for the transfer group (703.6 min vs. 394.5 min, p < 0.0001), while comparable figures were noted for groin puncture to reperfusion time (43.9 min vs. 45.1 min, p = 0.7071) and ICU length of stay (70.8 hours vs. 59.3 hours, p = 0.7071) between the two cohorts. Similar rates were also seen for successful reperfusion (p = 0.2348), sICH (p = 0.4933), favorable 90-day functional outcomes (p = 0.9457), mortality (p = 0.8534), and composite complications during hospitalization (p = 0.5779).

Conclusion:
Although we observed significantly longer time intervals from symptom onset to initiation of mechanical thrombectomy in patients transferred from outside facilities, there were no adverse consequences on patient outcomes.
Abstract TP291: Near-Infrared II Photobiomodulation Protects Against Stroke via Endothelial Nitric Oxide Phosphorylation
Authors: Yokomizo Shinya , Bragin Denis E , Gerashchenko Dmitry , Huang Paul , Kashiwagi Satoshi , Atochin Dmitriy N
Published: February 2024

Since endothelial dysfunction is implicated in stroke pathogenesis and is featured with suppressed endothelial nitric oxide (NO) synthase (eNOS) and NO deficiency, restoring endothelial NO represents a promising approach to treating stroke injury. We have shown that near-infrared II (NIR-II) laser treatment enhances the phosphorylation of eNOS at serine 1176 (S1176) and augments NO production. Here, we further determine the beneficial effect of NIR-II laser on stroke injury. Wild-type (WT) C57BL/6J and unphosphorylatable eNOS mutant mice with S1176A mutation (S1176A) were treated by NIR-II laser (1064 nm) at an irradiance of 50 mW/cm2 (5 min daily for 4 days) prior to the middle cerebral artery occlusion (MCAO, 30 min) by a filament. The ischemic and reperfusion (30 min) values of cerebral blood flow (CBF) were confirmed by laser Doppler flowmetry. Neurological deficit and infarct volume was evaluated 48 h after reperfusion. One- and two-way ANOVAs and the Kruskal-Wallis followed by Dunn's tests were used for statistical evaluation. The NIR-II laser-pretreated WT mice demonstrated significantly increased CBF reperfusion and decreased infarct volume compared with untreated mice. The neurologic scoring showed less severe deficits in the laser-treated mice than in the non-treated mice (1.1 vs. 1.8). To determine the involvement of S1176-dependent eNOS phosphorylation in NIR-II effects, we further treated S1176A mice. MCAO followed by reperfusion resulted in decreased CBF and an increased infarct volume in S1176A mice compared to WT mice. The infarct volume was significantly larger in laser-treated S1176A compared to laser-treated WT mice. Neurological deficit in S1176A mice showed no improvement with the laser pretreatment (2.3 vs. 2.6) and was significantly more severe in the laser-treated S1176A compared to the laser-treated WT mice. In conclusion, pretreatment with a 1064 nm laser at 50 mW/cm2 improved stroke outcomes via S1176 eNOS phosphorylation. NIR-II photobiomodulation offers a non-invasive and low-risk treatment for stroke. This new modality using a physical parameter could lead to the development of innovative therapies to prevent and treat a wide array of cerebrovascular diseases.
Abstract TP293: Juvenile Mice Are Susceptible to Infarct-Induced Neurodegeneration That Causes Cognitive Decline
Authors: Mayne Elizabeth W , Vanden Kelly , Paris Lu , Buckwalter Marion S
Published: February 2024

Introduction:
Over half of pediatric stroke survivors have permanent neurologic and cognitive deficits. Executive function and processing speed are two domains that are consistently affected on neuropsychiatric testing of pediatric stroke survivors. In adult mice, stroke triggers an immune-mediated, infarct-induced neurodegeneration that causes similar cognitive deficits. However, it is unknown whether similar pathophysiology causes children’s cognitive deficits after stroke.

Hypothesis:
We hypothesize that infarct-induced neurodegeneration occurs in a mouse model of pediatric arterial ischemic stroke.

Methods:
Male and female C57BL/6J mice were randomized to stroke or sham surgery at p28 to model stroke in late childhood and compared to adult 6-month-old mice. We used permanent distal MCAO followed by 60 minutes of hypoxia, an established model for focal ischemia that generates a purely cortical stroke. Mice underwent behavioral testing at 1- and 7-weeks post stroke with a standard Barnes Maze protocol used in adult mice, and with a protocol adapted for juveniles by increasing difficulty of the task. We performed immunostaining to quantify acute and chronic neuroinflammation, stroke size, myelination, and atrophy 3 days and 8 weeks after surgery.

Results:
At 7 weeks post-stroke, stroke mice performed significantly worse on Barnes Maze testing than sham mice (n = 7 stroke, 7 sham, p = 0.0265 2-way ANOVA with repeated measures) on the more difficult but not the standard protocol. Like adult mice, pediatric mice exhibited chronic B- and T- lymphocyte neuroinflammation in the stroke scar at 8 weeks after stroke and activated (CD68+) microglia in the scar and connected regions. Both groups had decreased subcortical myelin staining compared to age-equivalent sham mice. However, this decrease was more dramatic in pediatric mice at 65 ± 14% vs. 27% ± 9% in adults, p < 0.05).

Conclusions:
In a model of pediatric ischemic stroke, juvenile mice develop chronic neuroinflammation in the stroke and in white matter tracts that are connected to the stroke in conjunction with a delayed cognitive deficit. Our results suggest that infarct-induced neurodegeneration occurs after stroke in juvenile mice and may cause more severe dysmyelination than in adults.
Abstract TP295: Temporal Characterization of Immune Responses in the Rat Brain Following Ischemic Stroke Using In-Depth Flow Cytometry Panels
Authors: Zatulovskaia Yulia , Boshuizen Marieke C , Du Fang , Liang Xibin , Michie Sara , Bliss Tonya , Steinberg Gary
Published: February 2024

Introduction:
Rat models are widely used in stroke research as they are well suited for behavior studies and brain imaging techniques. However, methods for studying immune responses and identifying distinct leukocyte subsets in rats lag behind mice in part due to lack of specific antibodies for flow cytometry. Several flow cytometry antibody panels have been used to study the immune response of the rat brain after stroke, but they did not distinguish between pro- and anti-inflammatory macrophages, which is critical for stroke-induced neuroinflammation research. Here, we developed flow cytometry panels to measure myeloid and lymphoid leukocyte subsets in rat brain, blood, and spleen, with an emphasis on macrophage subtypes, and validated them in an ischemic stroke model.

Method:
Adult male (8-12 wk old) Nude and Sprague Dawley (SD) rats were subjected to distal MCAO. Ipsi- and contralateral hemispheres, blood, and spleen were collected and analyzed by flow cytometry at different time points post-stroke. Cell populations were sorted using FACS and characterized using qPCR or morphological analysis to confirm our FACS gating strategy.

Results:
We discriminated microglia, 3 monocyte/macrophage subsets, granulocytes, dendritic cells, NK cells, B cells, and T cells in the brain and periphery. The temporal profile of leukocyte subsets after stroke resembled those observed in mice, validating the reliability of our antibody panels: granulocytes and monocytes peaked in the first 2-3 days post-stroke, B and T cells peaked around 4-5 days, followed by a gradual increase of ‘microglia’ over 14 days. Using a combination of CD43 and His48 to differentiate monocyte/macrophage subpopulations, we observed a shift in these subsets over time, akin to the shift from pro- to anti-inflammatory macrophages reported in stroke-injured mouse brains. Notably, Nude rats differed from the SD rats in terms of His48 expression; SD rat brain monocyte/macrophage population was predominantly His48lo, while Nude rats had both His48lo and His48hi subsets.

Conclusion:
Our flow cytometry panels for rats distinguished leukocyte subsets, including monocyte/macrophage subpopulations, providing a valuable tool to study the complex immune responses in rat models of neurological disorders.
Abstract TP296: Circadian Rhythm Influences Stroke Outcomes Through Reverbα Remodeling
Authors: Kamat Pradip , Khan Mohammad B B , Siddiqui Shahneela , Hattaway Tyler G , Anas Affan , Baban Babak , DHANDAPANI Krishnan , Hess David C
Published: February 2024

Background:
Stroke leads to disability and death worldwide and evidence suggested that stroke severity is affected by the time dimension of the stroke. Rev-Erbα regulates the core circadian clock through repression of the positive clock element Bmal1 and controls circadian rhythm. However, it is unclear if Rev Erbα agonist (SR9009) treatment alleviates stroke severity in mice.

Hypothesis:
We found that at ZT06 stroke reduces the level of Rev-Erbα and elevates the inflammation and stroke severity. Therefore, we hypothesized that SR9009 treatment may reduce the inflammation and stroke severity in a mouse suture occlusion model.

Methods:
10 to 12 weeks C57BL/6J (Wild Type, n=5-10 mice/group) mice were randomly assigned to do stroke at the different time points of the day following zeitgeber time at ZT06 and Z18. Cerebral Ischemia was induced by occlusion of the middle cerebral artery (MCAO) for 60 min. stroke mice were treated with SR9009 (100mg/kg). Mice were treated at 1 hour and 24h after MCAO. The neurobehavioral assay was performed for the neurological deficit, motor deficit, and animal activity. Forty-eight hours after the stroke, TTC staining was done to estimate brain infarction, and the infarct area was measured using NIH-Image J software.

Results:
We found Rev Erbα were significantly (
p<0.001
) higher at ZT06 in naïve mice though Rev Erbα mRNA level significantly decreased at ZT06 (
p<0.05
) and ZT18 (p<0.05) stroke in comparison to sham. Interestingly treatment with SR9009 reduces stroke volume at ZT06 [F=14.99 (3, 23)
p<0.001
) in comparison to vehicle-treated stroke though no significant changes were observed at ZT18. There were no significant (
p>0.05
) effects of SR9009 on neurological deficit score, motor function, and corner test.

Conclusion:
This study demonstrates that SR9009 treatment reduces stroke volume and protection depends on the circadian time of stroke.
Abstract TP30: Exercise Postconditioning After Ischemic Stroke: Neuroprotection Through NGF/TRPV1-Mediated Astrocyte-Neuron Interaction
Authors: Li Fengwu , Bai Shangying , Wang Qingzhu , Geng Xiaokun , Ding Yuchuan
Published: February 2024

Introduction:
Astrocytes activation and interaction with neurons potentially affect stroke outcomes. Transient receptor potential vanilloid 1 (TRPV1) participated in reducing brain injury and nerve growth factor (NGF) affected TRPV1 activation. The present study investigated neuroprotection induced by exercise postconditioning (PostE) and elucidated the mechanistic regulation of astrocytes-neuron crosstalk via NGF/TRPV1 pathway.

Methods:
Adult Sprague-Dawley rats received 2 h middle cerebral artery (MCA) occlusion, followed by 24 h of reperfusion. The treadmill exercise was then initiated 24 h after reperfusion for 3 days (PostE). Brain damage was determined by infarct volume, edema and apoptotic proteins expression (Bcl-2, BAX and Caspase-3). Neuroplasticity was determined by dendritic spine staining and protein expression of BDNF, GAP-43, PSD-95 and synaptophysin. Neuronal TRPV1 expression, astrocyte proliferation and astrocytic NGF expression was assessed with immunofluorescence. Primary astrocyte-neuron Transwell cultivation were used to determine the secretion of astrocytic NGF activating neural TRPV1. Interaction between TRPV1 and NGF or TRPV1 and A-kinase anchoring protein150 (AKAP150) were detected by immunofluorescence and Co-IP.

Results:
PostE significantly decreased brain damage and induced neuroplasticity in ischemic rats. PostE induced astrocyte proliferation and astrocytic NGF secretion, which, in turn, activated TRPV1 expression in neuron. Either NGF or TRPV1 inhibitor eliminated the neuroplasticity, while NGF inhibitor decreased TRPV1 expression, suggesting the potential regulating role of astrocytic NGF on TRPV1. Primary cells cultivation demonstrated a NGF/TRPV1 and TRPV1/AKAP150 interplays showing astrocyte-neuron communication.

Conclusion:
PostE induced neuroprotection, which was mediated by the activation of astrocytes and their interaction with neurons through the NGF/TRPV1 pathway, highlighting the significance of astrocyte-neuron crosstalk in post-stroke recovery processes.
Abstract TP301: Tmem30a - Mediated Mitigation of Phosphatidylserine Exposure May Be a Novel Therapeutic Target for Brain Protection in Ischemic Stroke
Authors: Wu Di , Wu Chuanjie , Chen Jian , Ji Xunming
Published: February 2024

Cellular pathways of self-preservation are highly conserved and may represent powerful ways to protect tissue against injury and disease. Here, we use a combination of cell, mouse, rat, nonhuman primate, and human models to demonstrate the feasibility of evoking endogenous self-preservation pathways to protect brain tissue in stroke. The transmembrane protein 30A (
Tmem30a
), the β-subunit of P4-ATPases, helps maintain the asymmetric distribution of phospholipids in plasma membrane, especially phosphatidylserine (PS) in the inner leaflet.
Tmem30a
transcripts were increased in the penumbra in two types of animal models of stroke. The increased
Tmem30a
transcripts were associated with less PS exposure and neuron death in vitro and improved neurological outcomes and extended therapeutic window in vivo. Mechanistically,
Tmem30a
upregulation led to decreased levels of apoptosis-related markers. Moreover, we found that recombinant Annexin V protein can decrease PS exposure, reduce infarct volumes, and improve neurological impairments in wild mice after ischemia/reperfusion, but not in
Tmem30a
knockout mice and those receiving siRNA-
Tmem30a
. Lastly, we also observed that high Annexin V levels were associated with better outcomes in stroke patients with salvageable penumbra, but not in those without penumbral tissues. Overall, our findings reveal a previously unappreciated role of maintaining asymmetric distribution of phospholipids in protecting the penumbra in the context of clinically relevant reperfusion.
Tmem30a
is essential for PS-blocking dependent neuroprotection and might represent a potential new strategy for evoking endogenous self-preservation pathways to protect brain tissue after stroke.