bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP199: Genome Wide Association Study Of Intracranial Artery Dissection Reveals Potential Novel Loci
Authors: Chiba Tetsuya , Miwa Kaori , Takahashi Atsushi , Mizoguchi Tadataka , Yi Kenichiro , Hosoki Satoshi , Yoshimura Sohei , Toyoda Kazunori , Ihara Masafumi , Koga Masatoshi
Published: February 2022

Introduction:
Cervico-cephalic dissections (extracranial artery dissection [EAD] and intracranial artery dissection [IAD]) are defined by a mural hematoma in the wall of a cervical or intracranial artery and represent an important cause of stroke in young adults. It is relatively uncommon in the general population and likely to represent the ethnic difference with higher frequency of IAD in Asian than European populations. A few studies examining the genetic contributions for these phenotypes were reported. In EAD, the
PHACTR1
genes which had previously been identified as common genetic risk variants of hypertension and migraine was associated with EAD using genome-wide association study (GWAS) approaches.
RNF213
, an important susceptibility gene for Moyamoya disease was associated with IAD in one small study (n=24) using a candidate-SNP analysis but no GWAS of IAD have been reported so far. We performed GWAS to identify common variants associated with IAD.

Methods:
A total of 100 Japanese patients with IAD based on imaging diagnostic criteria from multidisciplinary expert consensus were prospectively enrolled in National Cerebral and Cardiovascular Center from March 2011 to August 2018.

Results:
We performed GWAS in 100 IAD cases (61 men, 50 years of median age[IQR, 45-61]) and 8380 controls from the Tohoku Medical Megabank Project which is a publicly available healthy cohort. No variant reached to genome-wide significant but 14 variants (7 regions) showed nominal significant association with IAD (p < 10
-5
). Among 14 variants, rs73828631 on
RBMS3
gene showed highest association with IAD (odds ratio = 2.16, 95% confidence interval = 1.59-2.92; P = 3.08 х 10
-7
).
RBMS3
was previously identified as genetic loci associated with brain aneurysm. According to the Genotype-Tissue Expression (GTEx) project database,
RBMS3
is highly expressed in artery.

Conclusions:
We identified potential 14 variants associated with IAD. We need to increase the number of IAD cases for further confirmation.
Abstract TP2: Rehabilitative Effects Of Exercise Pattens On Functional Outcome After Ischemic Stroke
Authors: Li Fengwu , Bai Shangying , Geng Xiaokun , Ding Yuchuan
Published: February 2022

Introduction:
Although physical exercise has been demonstrated to augment recovery of the post-stroke brain, how exercise patten optimizes neurological outcomes post-stroke remains to be determined. Forced exercise containing a stressful component is reported to be better than voluntary exercise on functional recovery. The present study attempted to explore a suitable exercise patten for better functional recovery and stronger neuroplasticity.

Methods:
Sprague-Dawley adult rats were subjected to 2 h middle cerebral artery occlusion followed by reperfusion. Treadmill exercise (15m/min) was initiated 24 hours after reperfusion for up to 21 days. Rats were assigned to a control group entailing post-stroke rest or three exercise groups: 1) exercise 5 min and rest 5 min for 6 cycles (E5), exercise 10 min and rest 10 min for 3 cycles (E10), and exercise for 30 min without rest for 1 cycle (E30). Infarct volume was determined by TTC after 48 h. Motor and cognitive functions were tracked. Western blotting was used to assess the proteins expression for neuroplasticity, including GAP-43, PSD-95, synapsin I, and BDNF. Levels of corticosterone were measured using ELISA. Changes in gene expression of stress-induced heat shock proteins (Hsp) 27 and 70 were compared using real-time PCR.

Results:
E30 but not E5 and E10 exercise models reduced brain infarct. All the exercise protocols significantly induced neuroplasticity and functional outcomes in ischemic rats, with E30 being most effective on the neuroplasticity and neurorehabilitation. A significant increase in corticosterone level in E30 were observed, indicating physical stress endurance may actually lead to a decrease in the resultant damage to the brain after an ischemic attack. mRNA expression of Hsp 27 and 70 were increased in E30, suggesting increasing response to physical stress in terms of the protection against cerebral ischemia.

Conclusion:
These findings contribute to the growing body of literature regarding the positive effects of long-term treadmill exercise on neuroplasticity and functional outcome. Additionally, the results suggested that physical stress played a role in the biochemical processes underlying exercise-induced post-stroke neuroplasticity.
Abstract TP204: Discharge Statin Practices For Young Stroke Patients In A Stroke Clinical Network
Authors: Choi Sun Gyeong , Morawo Adeolu O , Solomonow Jonathan , Mehndiratta Prachi , Yarbrough Karen L , Clark Kimberly , Cole John W , Cronin Carolyn A , Kittner Steven J , Nunez Joel , Phipps Michael S , Schrier Chad , Wozniak Marcella A , Williams Devin , Chaturvedi Seemant
Published: February 2022

Background:
Despite the association of statin use and lowered recurrent stroke and mortality, some studies suggest young stroke patients do not receive the same intense targeted treatment medical therapies for secondary stroke prevention as older patients. Our specific objective was to determine if there were differences in statin medication discharge practices provided to young ischemic stroke patients within a Stroke Clinical Network. The Stroke Clinical Network consists of nine stroke centers located in rural, suburban and urban geographical regions.

Methods:
The GWTG registry was queried (FY 2017-2021) to identify ischemic stroke patients to determine statin discharge practices using the following criteria: sex, race, age groups ≥18-39 and ≥40-49, LDL levels < 100, 101-129 and > 130, diabetes, HTN, and smoking status. Chi squared tests of proportions were used to evaluate significant relationships between subgroups.

Results:
Among 1,294 young ischemic stroke patients: 53% (682/1294) were Black and 38% (493/1294) White; mean age 40.9 years (SD +/-7.21years). Men, blacks, patients older than 40 and diabetics were more likely to be discharged on a statin. There was a direct correlation between sex, race, age, LDL level and diabetes with statin discharge practices. There was no difference in statin discharge practices between smokers and nonsmokers.

Conclusions:
Opportunities to improve compliance with obtaining LDL levels upon admission and prescribing statins at discharge exist. Increasing statin administration in the young stroke patient population reflects best practice and will decrease mortality and morbidity.
Abstract TP206: Vascular Risk Factors And Stimulant Use Among Stroke Patients
Authors: Cohen Audrey S , Potestas Jesse A , Sha Nidha , Almohamad Maha , JEONG JOOEUN , Buddha Mrinalini , Spellman Mackenzie L , Schmitz Joy , Stotts Angela L , Lane Scott D , de Dios Constanza I , Walss-Bass Consuelo , Savitz Sean , Green Charles , Sharrief Anjail Z
Published: February 2022

Background:
In 2019, an estimated 7.3 US million adults had used stimulants in the past year. Stimulant use is associated with increased stroke risk, yet the prevalence of common stroke risk factors (RFs) in patients who use stimulants is not well described. We sought to examine the association between stimulant use and the presence of stroke risk factors (RFs) in stroke patients.

Methods:
We conducted an IRB approved retrospective review of ischemic and hemorrhagic stroke patients admitted 9/2019 through 9/2020. Inclusion criteria were age ≥18 and completion of a urine drug screen (UDS) on admission. Logistic regression was used to model the association of RFs (hypertension, type 2 diabetes (DMII), hyperlipidemia, atrial fibrillation, and coronary disease) to acute stimulant use, adjusting for socio-demographic characteristics.

Results:
Among 1878 patients screened, 814 (43.3%) had a UDS. UDS was more common in younger (median age 60 vs 67), male (60.4% vs 47.6%) and Black (35.6% vs 27.5%) and Hispanic (22.0% vs 21.6%) patients. Of those with UDS, 72(8.84%) had cocaine and/or amphetamine detected and 660 (81.08%) were UDS negative. After controlling for age, sex, race, and insurance status, hypertension (OR 2.28, 95%CI 1.17-4.41) was positively associated with stimulant use while DMII was negatively associated (OR 0.39, 95%CI 0.19-0.81). Other RFs were not associated with stimulant use.

Conclusion:
Despite being younger, stroke patients with stimulant-positive UDS had a higher prevalence of hypertension, a leading risk factor for recurrent stroke, than UDS-negative patients. This group may represent a high-risk population that may benefit from targeted interventions for secondary stroke prevention. Differences in screening by sex, race, and age may lead to missed opportunities for assessment of recurrent stroke risk. A standard approach to drug screening may eliminate these biases.
Abstract TP208: Prevalence Of Adverse Cerebrovascular Events In Hypertrophic Cardiomyopathy Patients With And Without Atrial Fibrillation: A Systematic Review And Meta-analysis
Authors: Ye Tiffany Tze Shan T , Siah Qi Zhuang , Tan Benjamin Y , Ho Jamie S , Syn Nicholas L , Teo Yao Hao , Teo Yao Neng , Yeo Leonard L , Sia Ching-Hui
Published: February 2022

Introduction:
Hypertrophic cardiomyopathy (HCM) predisposes to adverse cerebrovascular events (ACEs) including ischaemic stroke, transient ischaemic attack (TIA), thromboembolic event (TEE) and peripheral embolism (PE). Concomitant atrial fibrillation (AF), which is more prevalent in the HCM population, confers even higher risk. Our aims are to report the prevalence of ACEs in HCM patients and to determine the additional clinical risks of AF on the prognosis of this population.

Methods:
A systematic literature search was performed on PubMed, Scopus, Embase/ Ovid and Cochrane library from inception to 20
th
March 2021. No limitations on language or date of publication were applied. The primary outcome of this review was to examine and compare the prevalence of ischaemic stroke in the HCM population with or without AF. Secondary outcomes were to identify their risk of non-stroke clinical outcomes such as TIA, non-specified TEE and PE. Non-specified TEE in our paper only referred to thromboembolic events whereby their types were not specified in the included studies. Meta-analysis was performed using StataSE 16 software, and heterogeneity was assessed using

I
2

test.

Results:
A total of 713 studies were identified, and 35 articles with 42,570 patients were included. The pooled prevalence of stroke/ TIA was 7.45% (95% confidence interval [CI] 5.80 - 9.52,
p
= 0.000) across 24 studies in the overall HCM population of 37,643 patients. AF contributed to a significantly higher risk of non-specified TEE (Risk ratio [RR] 4.49, 95% CI 1.88 - 10.73,
p
= 0.0007,

I
2

= 87.0) and total stroke/ TIA (RR 3.26, 95% CI 1.75 - 6.08,
p
= 0.0002,

I
2

= 76.0) in our study population. Within the apical HCM (ApHCM) population, the prevalence of stroke/ TIA was 9.30% (95% CI 6.64 - 12.87,
p
= 0.316).

Conclusion:
Our study concludes that concomitant AF diagnosis increases the risk of developing thromboembolic events and the stroke-related mortality rate. Although the prevalence of stroke/ TIA in the ApHCM subtype was slightly higher than the overall HCM population, further studies investigating the clinical outcomes of HCM subtypes are warranted.
Abstract TP212: Elevated LDL Cholesterol And Cardiovascular Outcomes In Adult Cancer Survivors And General Population Without History Of Cancer
Authors: Kim Kyuwoong , Oh Sanghyun , Lee Jihwan , Hong Yoo S.
Published: February 2022

Introduction:
Whether the contribution of elevated low-density lipoprotein (LDL) cholesterol to cardiovascular outcomes differs between adult cancer survivors and general population without history of cancer remains uncertain.

Hypothesis:
Elevated LDL cholesterol (≥130 mg/dL/≥3.36 mmol/L) is associated with incident cardiovascular disease (CVD) and the magnitude of this association is stronger in adult cancer survivors compared to the general population without history of cancer.

Methods:
Individuals ≥19 years of age were enrolled in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in 2002 with follow-up through December 30, 2015. In this study, we included adult cancer survivors without history of CVD and statin treatment who survived more than 1 year after the first cancer diagnosis and their age-and-sex matched control with 1:1 ratio. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CIs) from Cox proportional hazards model adjusted for shared CVD risk factors between adult cancer survivors and the general population. Q-statistic was used to compare the difference in the magnitude of elevated LDL cholesterol-CVD associations between the two populations.

Results:
Between January, 2003 and December, 2006, 5,163 adult cancer survivors and their matched control (N=5,163) were identified in the NHIS-NSC. The adjusted HRs and 95% CIs for incident CVD among adult cancer survivors and the general population with elevated LDL cholesterol, as compared to those without, were 1.87 (95% CIs: 1.22-2.87) and 1.14 (95% CIs: 0.73-1.76), respectively. However, the difference in contribution of elevated LDL cholesterol to incident CVD between the two populations was not statistically significant (
P
heterogeneity
=0.114).

Conclusion:
In this population-based cohort, we found an association between elevated LDL cholesterol and incident CVD, specifically in adult cancer survivors. These findings suggest that adult cancer survivors with elevated LDL cholesterol may need additional clinical attention for cardiovascular health.
Abstract TP215: Principal Hospital Admission Of Hypertension Foreshadows 3-month Ischemic And Hemorrhagic Stroke
Authors: Shu Liqi , Yaghi Shadi , Furie Karen L
Published: February 2022

Introduction:
Hypertension is a well-recognized risk factor for acute ischemic stroke (AIS) and intraparenchymal hemorrhagic (IPH). We performed a nationwide analysis to evaluate the rate of AIS and IPH readmission comparing patients with hypertension as a principal versus non-principal diagnosis.

Methods:
Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included patients with index admission diagnosis (principal or non-principal) of hypertension from 2016 to 2018. Hypertension, AIS, IPH, and other diagnoses were identified based on standard ICD-10 CM codes. Patients with AIS or IPH diagnoses during the index admission were excluded. We determined post-discharge 90-day admission trends by Kaplan-Meier estimates in patients with principal versus non-principal diagnosis of hypertension. We then constructed Cox regression models to determine associations between principal diagnosis of hypertension and AIS or IPH admission rates, with adjustment to age, gender, insurance type, zip code income quartile, index admission disposition, and Elixhauser comorbidities.

Results:
Of the 36,173,682 patients identified, 586,613 (1.62%) had a principal diagnosis of hypertension during the index admission. Patients with a principal diagnosis of hypertension were more likely to have an AIS or IPH during 90-day follow up versus non-principal diagnosis of hypertension (Figure). In the Cox regression model after the aforementioned adjustments, a principal diagnosis of hypertension was significantly associated with AIS (HR 2.37, 95% CI 2.23-2.53, P < 0.001) and IPH admission (HR 2.25, 95% CI 1.97-2.56, P < 0.001).

Conclusion:
Patients with hypertensive conditions warranting hospitalization as principal diagnosis are at increased risk of AIS and IPH in the first 90-days after discharge. Post-discharge planning should include intensive ambulatory blood pressure monitoring and control by outpatient providers.
Abstract TP216: Ischemic Stroke In Patients With Cancer Compared To Ischemic Stroke In Patients Without Cancer - A Cohort Study Using Synthetic Data
Authors: Lun Ronda , Siegal Deborah , Ramsay Tim , Dowlatshahi Dar
Published: February 2022

Background:
Patients with cancer are at an increased risk for ischemic stroke (IS) compared to those without cancer. The objectives of this study are 1) to examine risk factors for stroke in cancer and non-cancer patients, and 2) to identify predictive factors for recurrent IS in cancer patients.

Methods:
We performed a retrospective cohort study using MDClone, a platform that produces synthetic datasets based on real health system data from the Ottawa Hospital Data Warehouse. We analyzed all subjects with a diagnosis of cancer (excluding non-melanoma skin cancer or primary central nervous system malignancies) and IS within a 2-year period preceding and following their cancer diagnosis, and all IS patients without cancer, from the same time period (2000-2019). Patients were followed until May 2019. A forward selection, stepwise multivariate logistic regression model was used to assess the association between recurrent IS (primary outcome) and baseline characteristics. A sensitivity analysis was performed with only survivors in the cancer cohort.

Results:
We analyzed 10,875 subjects with IS: 1,250 had cancer and 9,625 did not. In cancer subjects, there was a higher prevalence of chronic obstructive pulmonary disease (8.4% vs 4.7%), previous IS (1.9% vs 0.1%), and previous venous thromboembolism (VTE) (8.3% vs 1.5%); the prevalence of atrial fibrillation and vascular risk factors was similar between the two groups. Recurrent IS occurred in 11.0% of cancer subjects and 12.1% of non-cancer subjects. In cancer subjects, the only significant predictor of recurrent IS was previous IS (OR 3.8, 95%CI 2.6 - 5.6). A sensitivity analysis of survivors amongst cancer subjects revealed an even stronger relationship between previous IS and recurrent IS (OR 4.4 95%CI 2.7 - 7.0). In the non-cancer subjects, significant predictors for recurrent IS include older age, while hypertension, dyslipidemia, and history of hemorrhagic stroke were negative predictors of recurrent IS.

Conclusion:
We found cancer patients with IS have a higher prevalence of COPD, previous IS and VTE, and that previous IS is an important predictor of recurrent IS in cancer patients. These results highlight the importance of identifying optimal secondary prevention treatments in cancer patients.
Abstract TP228: Sex Specific Predictors Of Short Term Stroke Readmission After Hypertensive Urgency: Insights From National Readmission Database
Authors: Elsharnoby Hadeer , Maraey Ahmed , Younes Ahmed , Elzanaty Ahmed , Kayani Waqas , Rahman Hamood , Kichloo Amir
Published: February 2022

Background:
Short term outcomes of patients hospitalized with hypertension urgency defined as sudden elevation of Blood pressure above 180 systolic or 110 diastolic is poorly studied in literature. Uncontrolled Hypertension is a major risk factor of stroke. Sex differences exist in stroke presentation and risk factors.

Objective:
To evaluate the sex specific predictors of short term (90-day) readmission with stroke in patients hospitalized with hypertension urgency.

Methods:
The study is a retrospective analysis of National Readmission Database (NRD) of years 2016-2018. Adult patients admitted with a primary diagnosis of hypertension urgency were included. Patients were excluded if they had stroke or transient ischemic attack (TIA) in index admission. October to December admissions were excluded to allow for 90 day follow up. Univariate logistic regression was performed on each variable. Variables with a p value >0.2 were included in multivariate logistic regression model (figure1).

Results:
A total of 104813 patients (58% female) included in our cohort of whom 1057 (1%) were readmitted with ischemic stroke or TIA within 90 days. Mean age of stroke readmissions was higher in female (68±16 vs 61±14 years, p<0.001). Diabetes Mellitus was an independent predictor of stroke readmission in both sexes. Independent predictors specific to females were peripheral vascular disorders (aOR:1.60 95% CI[1.13-2.28], P=0.008) and Hypothyroidism (aOR: 1.38, 95% CI[1.02-1.85], P=0.035). Independent predictor specific to males was age (aOR: 1.016, 95% CI [1.005-1.027], P=0.005). Paradoxically, prior CABG was associated with decreased risk of stroke readmission in females (aOR: 0.39. 95% CI[0.20-078], P=0.007) but not in males (P=0.229).

Conclusion:
We identified several sex specific predictors of 90-day readmission with stroke in patients admitted with hypertensive crisis. Knowledge of these predictors would help identify patients at risk and improve quality of care.
Abstract TP229: Prevalence Of Atrial Cardiopathy In Patients With Esus And Other Etiologies
Authors: Zurru Maria C , Balian Natalia , Luzzi Ariel , Cea Clarisa , Lopez Armaretti Marianela , Martinez Mariana , Baroni Maria Verónica , Alonzo Claudia
Published: February 2022

Objective:
To investigate the prevalence and clinical determinants of atrial cardiopathy in patients with embolic stroke of unknown source (ESUS) vs other subtypes of stroke.

Material and Method:
1881 consecutive patients with ischemic stroke, we compared the prevalence of atrial cardiopathy between ESUS patients and patients with ischemic stroke related to large artery atherosclerosis (LAA) and small vessel disease (SVD). Baseline characteristics were also compared between ESUS and other etiologies. We exclude 680 patients with cardioembolism due to atrial fibrillation, other causes of stroke 134 patient and 295 transient ischemic attack.

Results:
690 (37,2%) patients met ESUS diagnostic criteria, while others were classified into LAA (n = 397, 21,105%) and SVD (n = 794, 42,21, %). Prevalence of atrial cardiopathy was higher in ESUS patients compared to noncardioembolic stroke patients (27.6% ESUS vs 11.1% LAA, p= 0.001; and 27.6 % ESUS vs 10,9 SVD, p = 0.001). ESUS patients were younger, with lower prevalence of hypertension and higher higher total cholesterol and low-density lipoprotein levels.

Conclusions:
prevalence of atrial cardiopathy is higher in ESUS than in nonembolic stroke. it is still unclear if they may benefit from anticoagulation. Further efforts are necessary to provide better characterization of the ESUS population in order to develop better stroke preventive strategies.
Abstract TP230: Dietary Behaviors Following Stroke: A Qualitative Study Of Stroke Survivor Perspectives
Authors: Bailey Ryan , Ipsen Miranda
Published: February 2022

Purpose:
Following a healthy dietary pattern (e.g., Mediterranean diet) is recommended for secondary stroke prevention due to its beneficial effect on stroke risk factors. However, stroke-related disability may hinder the performance of dietary behaviors (i.e., accessing, preparing, and consuming food), which are necessary and preparatory to consuming healthy foods. The purpose of this study was to characterize dietary behaviors in stroke survivors.

Methods:
This study is a secondary analysis of focus group data from 15 chronic (≥6 months) community-dwelling stroke survivors and 10 care-partners. We used a qualitative descriptive approach and inductive content analysis to examine how stroke survivors perceive dietary behaviors.

Results:
Three key themes emerged (see the table for illustrative quotations). First, changes in body functions/structures (e.g., hemiparesis, balance) result in dietary behavior activity limitations (e.g., difficulty grocery shopping, meal preparation). Second, environmental supports (e.g., care-partners, adaptive equipment) and activity modification (e.g., using pre-cut foods, dining out) are used to overcome dietary behavior limitations. Third, negative affect (e.g., dissatisfaction, frustration) and activity limitations lead to participation limitations (e.g., not being able to perform dietary behaviors independently, not being able to socialize when dining out).

Conclusions:
Dietary behaviors are negatively impacted following stroke, but environmental supports and compensatory strategies may be implemented to overcome activity limitations. Despite guidelines that recommend following a healthy dietary pattern, adherence to such guidelines may be difficult due to stroke-related disability. Further research is needed to develop and test interventions to facilitate dietary behaviors to help survivors adhere to these guidelines and reduce risk of recurrent stroke.
Abstract TP231: Irisin, Elicited By Low Frequency Whole Body Vibration Or Exogenously, Improves Post-Stroke Cognition And Reduces Infarct Volume In Middle-Aged Rats
Authors: Kerr Nadine , Sanchez Juliana , MORENO WILLIAM JAVIER , Furones-Alonso Ofelia E , Dietrich W. Dalton , Bramlett Helen M , Raval Ami P
Published: February 2022

Significance:
Low frequency whole body vibration (LFV) at 40 Hz, a low impact form of exercise, for a month following mild transient middle-cerebral artery occlusion (tMCAO) reduces infarct volume and improves motor function in reproductively senescent, middle-aged female rats (1). In humans, LFV was shown to increase circulating levels of irisin, a skeletal muscle-derived hormone. Irisin has also been shown to play a crucial role in preserving mitochondrial function, preventing oxidative stress, and elevating expression of BDNF, among other neuroprotective measures. The current study aims to investigate the efficacy of LFV in ameliorating post-tMCAO cognitive deficits and to determine the putative role of irisin in conferring the benefits of LFV in middle-aged rats.

Methods:
Middle-aged rats of both sexes (5-8) were randomly assigned to tMCAO (90 min), or sham surgery followed by exposure to either LFV (twice a day for 15 min each for 5 days a week over a month) or no LFV treatment groups. Following the last LFV treatment, rats were tested for hippocampus-dependent learning and memory using a water maze followed harvesting brain and blood samples for histopathological and inflammatory marker analyses, respectively. In a parallel experiment in the absence of LFV, middle-aged female rats were randomly assigned to either saline or irisin treatment following tMCAO. Recombinant irisin was purchased from PeproTech (Rocky Hill, NJ). Rats were treated with irisin (0.2 μg/g BW; IP) or saline for a month followed by their brains were assessed by histopathology.

Results:
Post-tMCAO LFV significantly lessens cognitive deficits in rats of both sexes. It also significantly decreased circulating pro-inflammatory cytokines and increased serum levels of native irisin. Quantification of infarct volume irisin-treated rats demonstrated that, compared to saline, infarct volume was significantly reduced. Saline treatment resulted in 234 ± 30 mm
3
, while irisin treatment yielded 128 ± 34 mm
3
(p<0.05) of infarct volume.

Conclusion:
Irisin, either as elicited by LFV or administered exogenously without LFV, regulates brain metabolism and inflammation and its beneficial effects can be stimulated by LFV.Reference: 1. Raval, A.P., et al., Int J Mol Sci, 2018.
19
(9).
Abstract TP237: Characterization Of Vascular Smooth Muscle Cells Derived From Induced Pluripotent Stem Cells Of Moyamoya Disease Patients; Comparison With Endothelial Cells
Authors: Tokairin Kikutaro , Ito Masaki , Fujimura Miki
Published: February 2022

Introduction:
Moyamoya disease (MMD) is a rare cerebrovascular disorder with unknown etiology. Although vascular smooth muscle cells (VSMCs) are known to be involved in the histopathology of MMD, VSMCs have not been biologically characterized in contrast to well-characterized endothelial cells (ECs).

Methods:
VSMCs were differentiated from neural crest stem cells (NCSCs) using induced pluripotent stem (iPS) cell lines established from peripheral blood mononuclear cells of healthy control subjects and MMD patients with
RNF213
founder polymorphism (n=3, each). Cellular proliferation, migration, contractile, and array-based transcriptome profiles of VSMCs were compared between the groups. The transcriptome profile of VSMCs was also compared with ECs using the same iPS cell lines and analysis platform.

Results:
Homogeneous spindle-shaped cells were differentiated from NCSCs. These cells exhibited similar expression of myosin heavy chain-11, calponin, smooth muscle protein 22α, and α-smooth muscle actin in both groups, and real-time PCR analysis further demonstrated no expression of CD31 and CD34, thereby suggesting the features of differentiated VSMCs.

No significant differences in the proliferation, migration, and contractile profiles of VSMCs were observed between the two groups. Transcriptome analysis demonstrated similar gene expression profile of VSMCs in MMD and control subjects, resulting in six differentially expressed genes (DEGs, 4 upregulated and 2 downregulated genes in MMD), whereas the iPS cell-derived ECs showed distinct transcriptome profile in MMD patients as compared to control subjects with 120 DEGs (78 upregulated and 42 downregulated genes in MMD).

Conclusions:
This study showed similar biological and transcriptome features in VSMCs, in contrast to ECs with distinct transcriptome profile between MMD patients and control subjects. Thus, ECs, rather than VSMCs, may play a major role in the pathophysiology of MMD.
Abstract TP244: Formation Of Neutrophil Extracellular Traps During
In Vitro
Stroke Facilitates Endothelial Cytotoxicity
Authors: Abdullah Abdulrahman , Wu Michael , Wang Kendra , Yin Junxiang , Ahmad Saif , Ducruet Andrew F , Ahmad Abdullah S , Waters Michael F
Published: February 2022

Background:
Stroke is one of the leading causes of death and disability. Some aspects of inflammation are known to be detrimental and arresting these aspects may improve stroke outcomes. Neutrophils are critical neuroinflammatory mediators and among the first immune cells to respond to the onset of stroke. As the stroke evolves, neutrophils may expel their intracellular contents, referred to as Neutrophil Extracellular Traps (NETs), in a process called NETosis. NETs increase microvascular occlusion and lead to further progression of stroke. However, the interaction of NETs with the cerebral microvascular endothelial cells and the effect of this interaction on stroke outcomes is poorly understood. This project aims to investigate this relationship.

Methods:
Leukocytes and plasma from C57BL/6 wildtype mice were isolated from whole blood. The leukocytes were then plated in 24-well plates and divided into control and Oxygen Glucose Deprivation (OGD) simulating a stroke environment in vitro. Thereafter, leukocytes were subjected to immunofluorescent staining for neutrophils (Ly6G), and the NETosis markers citrullinated histones (CitH3) and dsDNA. Media from both groups was assayed for Neutrophil Elastase, IL-6, TNF-α, and lactate dehydrogenase (LDH). The remaining media was used to treat primary microvascular endothelial cells to assess inflammation and cell death.

Results:
Ly6G antibody staining verified that most of the leukocytes plated were neutrophils. The CitH3 and dsDNA immunostaining confirmed induction of NETosis in the OGD group. We also found a significant increase in IL-6 and LDH levels suggesting significant inflammation and cell death in OGD treated leukocytes. Exposure of endothelial cells with NETs enriched media obtained from OGD exposed leukocytes resulted in significant decrease in cell count and increase in IL-6 and LDH levels, suggesting that NETs promoted inflammation and death in the endothelial cells. Nuclear staining of the endothelial cells also exhibited significant decrease in cell count in cohorts treated with the OGD exposed leukocyte media.

Conclusion:
These pilot data suggest that NETosis may contribute to the cytotoxicity of cerebral endothelial cells during stroke and serve as a potential therapeutic target.
Abstract TP246: The Role Of Pericytes In Ischemic Stroke
Authors: Lummis Nicole , Daneman Richard
Published: February 2022

Stroke is one of the leading causes of death worldwide. Loss of blood flow, typically from a blood clot that occludes the cerebral vasculature, causes ischemia, tissue death, and long-term cognitive deficits. Following stroke, the blood-brain barrier (BBB) is damaged, causing leakage of ions, molecules, toxins, and immune cells into the brain. Pericytes are a perivascular cell that is important for neurovascular growth and stability, and have been reported to both aid vascular regrowth and transdifferentiate into pro-inflammatory cells after ischemic injury. However, markers used to identify pericytes non-specifically label other cell types, making it unclear whether these studies are specifically identifying pericytes. In order to understand how pericytes adapt to ischemic injury, we modeled stroke in mice with distal middle cerebral artery occlusion (dMCAO) and lineage traced these cells with two novel pericyte markers: TBX18 and Atp13a5, allowing us to track ischemia-induced changes in pericytes and their progeny. We discovered that pericytes in the ischemic core die over the first three days following injury, while surviving pericytes proliferate in response to injury, and investigated how pericyte identity changes with histology and single cell RNA sequencing.
Abstract TP251: CRISPR-engineered Mouse Neural Cells Expressing An Optimized Manf Variant Reveals Mechanisms Of MANF Neuroprotection
Authors: Llera Ted D , Singhal Neel S , Ma Dengke
Published: February 2022

Introduction:
Hibernating mammals have evolved physiological strategies to cope with harsh winters by markedly reducing their metabolic rate and core temperature. Interestingly, neural stem cells derived from Arctic ground squirrels (AGS) also possess resilient cell biological processes that preserve cell integrity during hypoxia and exposure mitochondrial toxins. We identified AGS mesencephalic astrocyte-derived neurotrophic factor (MANF) as a key cytoprotective gene in diverse survival screens of mouse neural cells expressing an AGS cDNA library.

Hypothesis:
We hypothesize that adaptively evolved amino acid substitution in AGS MANF confers metabolic stress resilience by modulating actions of MANF including sulfatide-binding, reducing endoplasmic reticulum (ER) stress and altering mitochondrial metabolism.

Methodology:
CRISPR-Cas9 knock-in (KI) gene editing was utilized to generate mouse neural cells harboring the AGS
Manf
allele to allow for analysis of the beneficial effects of the AGS amino acid substitutions in cell survival to metabolic stress, mitochondrial metabolism, MANF protein stability, and sulfatide binding.. We also tested AGS compared to human MANF with regard to reducing ER stress under hypoxia, hypothermia, and rotenone.

Results:
AGS MANF expression reduced ER stress markers compared to human MANF, and demonstrated increased stability following rotenone treatment further pointing to its important role regulating cellular adaptations to metabolic stress and imparting neuroprotection in our in vitro model. We gained key functional insights into how specific amino acid substitutions improve MANF stability to impart cytoprotection to metabolic insults. This detailed dissection of the AGS optimized adaptive stress response pathway can serve as a template for the development of new neuroprotective treatments.
Abstract TP255: Lymphocytes And Platelets In Extracted Thrombus May Indicate The Etiology Of The Thrombus. Results From The Itacat Multicentric Registry.
Authors: Pagola Jorge , Juega Jesus , Camacho Jessica , Dorado Laura , Rodriguez Maite , Hernandez-Perez Maria , Quesada Garcia Helena , Cardona Pedro , de la Torre Carolina , Deck Matias , Garcia-Tornel Alvaro , Requena Manuel , Rubiera Marta , Boned Sandra , Muchada Marian , Olive Marta , Ribo Marc , Piñana Carlos , Hernandez David , Rodriguez-luna David , Rodriguez Villatoro Noelia , SANJUAN Estela , tomasello alejandro , Alvarez Sabin Jose , Ramon y Cajal Santiago , Molina Carlos A
Published: February 2022

Aim:
We performed a histological and immune analysis of the clot in acute stroke patients to detect surrogates of stroke etiology.

Methods:
We conducted a prospective observational study of consecutive patients with acute stroke who underwent thrombectomy that obtained extracted thrombus (ITACAT study). Several staining were performed to evaluate red blood cells/fibrin (hematoxylin/eosin), platelets (CD61) and leucocytes (CD4, CD8 and CD20). All patients received CT angio to detect extra/intracranial vascular stenosis and 30-day cardiac monitoring to diagnose AF. According to TOAST classification the thrombi were classified in cardioembolic etiology CE (T-CE), due to symptomatic atherosclerosis (T-AT) and without any cause (T-CRYP). We excluded strokes due to double cause or incomplete workup.

Results:
Of the 117 patients: 30 were T-AT, 55 were T-CE and 32 were T-CRYP. T-AT patients were younger: T-AT 68 years (60-77) Vs. T-CE 75 years (68-80) Vs. T-CRYP 72 years (55-81) (p=0.034). T-AT group had higher percentage of CD4: T-AT 6.52% (4-13) Vs. T-CE (3.31% (12.9) Vs .T-CRYP 3.72% (1.5-12) (p=0.015) and lower percentage of CD61: T-AT 51.18% (34-68) Vs. CE 64.70% (19.56) Vs. CRYP 70.3% (19) (p=0.001). There were no correlation between CD4 and platelets. Both CD4 OR 1.05 (1-1.10) (p=0.020) and CD61 (OR 0.96 (0.94-0.98) (p=0.01) independently predicted T-AT from the age. Final analysis (n=400 cases) will be ended in September 2021.

Conclusions:
Patients with high percentage of CD4 and low percentage of CD61 are related to atherosclerosis etiology.
Abstract TP256: The Role Of Dietary Iron Restriction In The Pathophysiology Of Intracranial Aneurysm Rupture
Authors: Kamio Yoshinobu , Makino Hiroshi , Hokamura Kazuya , Imai Ryo , Kimura Tetsuro , Sugimura Sho , Umemura Kazuo , Kurozumi Kazuhiko
Published: February 2022

Background:
Iron is an essential element for maintaining vascular wall, however iron depositions in vascular wall cause tissue damage by oxidative stress via Fenton/Haber-Weiss reaction. We hypothesized that iron promotes intracranial aneurysmal formation and rupture through oxidative stress and vascular inflammation. Using a mouse model of intracranial aneurysm, we examined whether iron restriction reduces aneurysm formation and rupture.

Methods:
To induce aneurysm, we combined induced systemic hypertension (deoxycorticosterone acetate-salt hypertension) and a single injection of elastase (35mU) into the cerebrospinal fluid at the right basal cistern. The mice were divided into two groups and fed with iron restricted diet (IRD) (0.32mg/100g) or normal diet (ND) (600mg/100g) for 5 weeks.

Results:
IRD significantly reduced the aneurysmal rupture compared to ND (ND versus IRD: 76% versus 37%; P < 0.05). Whereas, there was no significant difference in the overall incidence of aneurysms between the ND and IRD groups (ND versus IRD: 68% versus 69%; P =1.00).

Conclusion:
Our data demonstrate that iron restriction reduces intracranial aneurysm rupture.
Abstract TP259: Neuroprotective Effects Of Ripk2 Deficiency In Experimental Ischemic Stroke
Authors: Larochelle Jonathan , Lavayen Bianca , Liu Lei , Tishko Ryland , Yang Changjun , Candelario-jalil Eduardo
Published: February 2022

Background:
Receptor-interacting serine-threonine protein kinase 2 (Ripk2) is involved in the signaling pathways of members of the NOD family of cytosolic pattern recognition receptors. Ripk2 has been implicated in the caspase-1 pathway of hypoxia and ischemia-induced neuronal cell death, as well as the pathology of neuroinflammatory diseases like multiple sclerosis. Ischemic stroke is characterized by brain injury resulting from initial hypoxia/ischemia-induced cell death and secondary neuroinflammation.

Hypothesis:
Since Ripk2 is implicated in both pathways, we hypothesized that the genetic deletion of Ripk2 will improve outcomes for animals after experimental stroke.

Methods:
We utilized
Ripk2
knockout (
Ripk2
-/-
) mice (3-4 months old) and subjected them to 45min of transient middle cerebral artery occlusion (tMCAO) along with wild-type (WT) control littermates. Infarct size was measured at 24h by TTC staining. RNA was isolated from the ipsilateral and contralateral cortices for RT-qPCR. Weight grip test, vertical grid test, and open field behavioral tests were conducted before and up to 21 days after tMCAO with novel object recognition and Y-maze tests occurring at day 28.

Results:
After 24h,
Ripk2
-/-
mice had significantly smaller infarct sizes than wild-type (WT) mice.
Ripk2
-/-
mice also had much lower expression of proinflammatory cytokines (
Tnfα, Il1β,
and
Il6
) and chemokines (
Ccl2
and
Cxcl1
) in the ipsilateral cortex relative to WT, implicating a diminished proinflammatory response to ischemia/reperfusion injury in
Ripk2
-/-
animals.
Ripk2
-/-
mice displayed significantly better neurological deficit scores compared to WT at 24h, 48h, 7d, 14d, and 21d post-tMCAO.
Ripk2
-/-
mice also performed much better than WT at acute time points in a battery of behavioral tests, such as the weight grip test, vertical grid test, and open field test. Neurological assessment via novel object recognition and Y-maze tests showed no difference between genotypes at 28d.

Conclusions:
Our findings support the hypothesis that Ripk2 plays a detrimental role in the pathology of ischemic stroke. Understanding Ripk2’s role in stroke pathology may reveal a novel therapeutic target for the treatment of ischemic stroke.
Abstract TP3: Seizures As Stroke Mimics In Ultra-early Treatment On A Mobile Stroke Unit: A Pilot Study
Authors: Kowalski Robert G , Schimpf Brandi , Ornelas David , Poisson Sharon N , Carrera Eduardo , Bernard Timothy J , Kluger Benzi M , Taylor Matthew R , Sillau Stefan , Jones William
Published: February 2022

Background:
Stroke mimics are often difficult to distinguish from true ischemic and hemorrhagic cerebrovascular accidents, and present a challenge for appropriate delivery of rapid stroke treatment. This is particularly true in ultra-early stroke care with Mobile Stroke Units (MSU), which administer tPA in the field, within minutes of symptom onset. We sought to evaluate and characterize stroke mimics during prehospital care with an MSU at a Comprehensive Stroke Center.

Methods:
The study compared patient and stroke characteristics, neurologic evaluation, and treatment between confirmed strokes and stroke mimics treated during a one-year pilot period on the MSU at a large urban medical center. Variables included patient demographics, NIHSS score, tPA administration, final diagnosis, and discharge disposition.

Results:
Between Jan. 15, 2016 and Jan. 9, 2017, 47 patients received prehospital management on the MSU, and 44 were admitted to UC hospital and had an available final diagnosis. Of these, 12 (27%) were stroke mimics. Mimics were younger [median age 60 (IQR 54-71) years, mimics vs. 68 (IQR 60-77) years, strokes], and were more often female (58%, mimics vs. 47%, strokes). Initial NIHSS score was lower for confirmed strokes [median 3 (IQR 2-10) strokes, vs. 6 (IQR 4-12) mimics], but severe strokes with a NIHSS score >17, were more common in strokes (16%, strokes vs. 0%, mimics). Of mimics, 6 (50%) were seizures, 2 (17%) migraine, 2 (17%) conversion, 1 (8%) encephalopathy, and 1 (8%) delirium. Thirteen (30%) of all patients were treated with IV tPA on the MSU, of whom 4 (31%) were mimics. Of mimics given tPA, 2 were seizures, 1 migraine and 1 conversion. Mimics were more likely to be discharged to home (64%, mimics vs. 46%, strokes) while strokes more likely received rehabilitation (23%, strokes vs. 9%, mimics).

Conclusions:
One third of patients treated on the MSU were stroke mimics, and among these the most common diagnosis was seizures. These results suggest vigilance is warranted for seizure, as well as further study of rapid EEG technologies to guide appropriate treatment for presentations that appear to be stroke, including antiepileptic drugs, in ultra-early MSU care of suspected CVA.
Abstract TP35: Stroke Nurse Navigation-Evolving Care Delivery To Effectively Meet The Needs Of Stroke Patients And Families
Authors: Buchinsky Kelly , Pope Leslie , Noah Patty , Hackett Chris , Cerejo Russell
Published: February 2022

Background:
Research indicates the importance of life-style modification, risk factor management, and medication and physician follow-up compliance in the prevention of stroke. Nurse navigators are in a unique position to influence this care. The pandemic changed post-acute management of stroke by requiring increased virtual care as opposed to in-person care. A known disparity existed in the number of touch points between the patients utilizing the patient portal versus those reached only by phone. We aimed to evaluate how changes in navigator workflow influenced the frequency of touchpoints, operating under the assumption that increased touchpoints will improve post-hospital care.

Methods:
A retrospective analysis was completed for acute stroke patients discharged from January 2020 - March 2021 for 4 certified stroke centers. We implemented standardized time intervals for patient outreach, regardless of modality. Initial outreach was completed within 48 hours to avoid potential gaps in care. Motivational interview calls were focused on education that included life-style changes, compliance, risk factor control and follow-up, which mirrored the mobile application’s education. Branded individualized education materials were created and sent to patients using US Mail or via the patient portal. New flowsheets were developed in the EMR for future data collection and reporting. Hand written notes and cards of encouragement were also sent reinforcing the counseling received. Linear regression analysis evaluated our primary outcome: the relationship between monthly touchpoints over time.

Results:
A total of 1935 patients were diagnosed with acute stroke, discharged and managed post-hospitalization for 90 days. During the 90 day episode, navigators interacted with patients for
M
= 4.64
SD
= 2.46. Regression analysis demonstrated a linear relationship between time and touchpoints (
p
<0.001). Navigators also reported intangible results from patient and family feedback related to support and care received.

Conclusions:
Stroke care is complex and requires ongoing patient and caregiver support. Increasing availability to stroke experts, such as nurse navigators, provides support and tools to improve post-hospital care.
Abstract TP47: Emergency Medical Services Time Intervals For Suspected Stroke Patients In The United States
Authors: Cash Rebecca E , Boggs Krislyn M , Richards Christopher T , Camargo Carlos A , Zachrison Kori S
Published: February 2022

Introduction:
Prehospital recognition and rapid transport of stroke patients by emergency medical services (EMS) is critical to optimize access to time-sensitive care. We aimed to describe EMS time intervals for suspected stroke patients in the U.S. and to quantify variation in EMS time intervals by geographic location and urbanicity.

Methods:
We conducted a cross-sectional evaluation of EMS 9-1-1 activations (i.e., calls for service) included in the 2018 and 2019 National EMS Information System. We included ground and air EMS activations for a scene response where a patient aged ≥18 years old with suspected stroke (EMS impression of I60-I63 or G45) was treated and transported by EMS. Time intervals for dispatch, response, scene, transport, and total prehospital time were calculated, stratified by ground and air transport type.

Results:
A total of 415,342 activations for suspected stroke were included, of which 98% were a ground transport. The overall median total prehospital time for ground transports was 35 minutes (IQR 27-45, 90
th
percentile 58; Table). Median total prehospital time for air transports was substantially longer at 56 minutes (IQR 43-70, 90
th
percentile 86). Times varied by census division and urbanicity with the shortest median total prehospital time of ground transports in the East North Central division (31 min, IQR 25-40) and urban areas (34 min, IQR 27-43) and longest times in the East South Central (39 min, IQR 30-52), rural (40 min, IQR 28-56), and frontier (44 min, IQR 29-63) areas.

Conclusions:
With ongoing focus on optimizing time-to-treatment for acute stroke interventions, prehospital transport can be targeted for quality improvement. While some variation is expected

due to geographical constraints, we found substantial variation in prehospital transport times for suspected stroke that may present opportunities for future improvement. These findings may inform health services research and policy efforts to improve stroke care access.