bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP228: Reversible Cerebral Vasoconstriction Syndrome: Presenting Symptoms, Incidence, and Outcomes in a Multi-State Cohort in the United States
Authors: Magid-Bernstein Jessica , Salehi Omran Setareh , Murthy Santosh B , Merkler Alexander E , Kamel Hooman
Published: June 2021

Introduction:
Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome of recurrent thunderclap headaches with transient cerebral vasoconstriction which can cause stroke. There are few population-based data on the incidence of RCVS as well as associated risk factors and complications.

Methods:
We performed a retrospective cohort study using administrative claims data from all nonfederal emergency department (ED) visits and hospitalizations in 11 U.S. states during 2016. Using
ICD-10
diagnosis code I67.841, we identified adult patients hospitalized with RCVS and evaluated associated diagnoses during prior, concurrent, and subsequent ED visits and hospitalizations. We used U.S. census data to estimate the age- and sex-standardized incidence of RCVS in the U.S. adult population. In a validation study, we reviewed the records of patients with a discharge diagnosis of RCVS and a random sample of patients with other cerebrovascular diagnoses at our medical center to estimate the sensitivity and specificity of the RCVS diagnosis code, and calculated the RCVS
2
score of patients with RCVS.

Results:
In our validation study, the sensitivity of the RCVS
ICD-10
code was 100% (95% CI, 66-100%) and the specificity 90% (95% CI, 74-98%); the median RCVS
2
score among patients diagnosed with RCVS was 6, supporting that the diagnosis code generally identified true cases of RCVS. In our statewide analysis, we identified 222 patients diagnosed with RCVS in 2016, equating to a U.S. incidence of 2.7 (95% CI, 2.4-3.1) per million adults per year. The mean age was 46.8 (±14.3) years, 63.5% of patients were white, and 77.5% were female. There were 17 ED visits (22% of all ED visits) for headache in the 3 months before RCVS diagnosis. During the RCVS hospitalization, the most common complications were subarachnoid hemorrhage (33.5%), followed by ischemic stroke (14.9%), intracerebral hemorrhage (9.3%), and seizures (9.3%). Most patients were discharged home after admission for RCVS (76.6%).

Conclusions:
Hospitalization with a recognized case of RCVS occurs in about 3 per million adults in the U.S. per year. Although majority of patients hospitalized with RCVS were discharged home, a substantial proportion had serious cerebrovascular complications.
Abstract WP229: Young African Americans With Stroke Have a Greater Burden of Multiple Risk Factors Than Their White Counterparts
Authors: Mehndiratta Prachi , Ryan Kathleen , Cole John W , Wozniak Marcella , Chaturvedi Seemant , Cronin Carolyn A , Phipps Michael , Merino Jose G , Dutta Tara , Kittner Steven J
Published: June 2021

Background:
Stroke in young adults accounts for 15-18% of all ischemic stroke (IS) cases and disproportionately affects African Americans (AfrAm). While it is well known that a higher prevalence of vascular risk factors, particularly HTN and DM, contributes to this excess risk, few studies have examined the potential contribution of the synergistic risk from multiple vascular risk factors.

Methods:
A population-based case-control study with 582 cases and 727 controls ages 15-49 was used to investigate the relationship of multiple risk factors and IS in young adults and compare AfrAM and White cases for the prevalence of multiple risk factors. Logistic regression analysis with adjustment for age, sex, and race was used to evaluate the association between the following mutually exclusive risk factor groups and IS: (a) Smoking alone, (b) Smoking+ HTN only, (c) Smoking + HTN +Obesity only (d) Smoking + HTN + Obesity +DM. The reference group for these analyses was those with no risk factors. Logistic regression with adjustment for age only was also used to compare AfrAM vs White cases for their prevalence in each risk factor group.

Results:
There were a total 218 cases with no risk factors. The odds of having an IS increased exponentially as the number of risk factors increased (OR 2.3, 95% CI 1.8 - 3.0, p <0.0001 for group a versus OR 16.5, 95% CI 4.8-56.1, p<0.0001 for group d). Young AfrAM cases were approximately 6 times more likely (25.3% vs. 4.3% p<0.0001) than White cases to be in the multiple risk factor group d.

Conclusion:
The risk of IS increases in an exponential manner in young adults with an increasing number of traditional risk factors. Compared to their White counterparts, young AfrAm IS cases are approximately 6 times more likely to have all 4 risk factors: smoking, HTN, DM and obesity. Risk factor synergy could contribute to the excess risk of IS among young AfrAm and our study emphasizes early screening for vascular risk factors in this subgroup.
Abstract WP231: Prevalence and Associated Metabolic Factors of Non-Alcoholic Fatty Liver Disease in Middle and Young-Old-Aged Acute Stroke Patients
Authors: Mori Takahisa , Yoshioka Kazuhiro , Chiba Nozomi
Published: June 2021

Introduction:
Non-alcoholic fatty liver disease (NAFLD) is reported to be a predictor of cardiovascular disease (CD). However, prevalence and associated metabolic factors of NAFLD in stroke middle and young-old-aged patients remain unknown.

Hypothesis:
In middle and young-old-aged stroke patients, prevalence of NAFLD on admission is high and its metabolic factors are body mass index (BMI), serum Albumin, serum glucose or HbA1c, serum total cholesterol (T-CHO) and triglycerides (TG), some serum fatty acids (FA) and aspartate aminotransferase / alanine aminotransferase ratio (AST/ALT ratio) as well as reported in ischemic heart disease.

Methods:
We included acute stroke patients who 1) were admitted from August 2016 to December 2018 and aged 40-79 years, 2) underwent abdominal ultrasonography and 3) took blood examination on admission. We evaluated prevalence and associated metabolic factors of NAFLD.

Results:
Among 1400 acute stroke patients, 660 patients met our inclusive criteria. Their median age was 70.5 years, 264 patients (40.0%) had NAFLD. In NAFLD and non-NAFLD patients, median age was 68 and 72 years (p<0.0001), BMI was 24.6 and 21.6 kg/m
2
(p<0.0001), Alb was 4.2 and 4.0 g/dl (p<0.0001), HbA1c was 6.0 and 5.8 % (p<0.0001), T-CHO was 212 and 200 mg/dl (p<0.001), TG was 134 and 93 mg/dl (p<0.0001), palmitic acid (16:0, saturated FA) was 717 and 619.6 μg/ml (p<0.0001), oleic acid (18:1, n-9 monounsaturated FA) was 659.7 and 552.4 μg/ml (p<0.0001), linoleic acid (18:2, n-6 polyunsaturated FA) was 786.5 and 721.9 μg/ml (p<0.0001) and AST/ALT ratio was 1.07 and 1.36 (p<0.0001), respectively. Stepwise logistic regression analysis by Bayesian information criterion showed that BMI (p<0.0001), TG (p<0.0001) and AST/ALT ratio (p<0.0001) and Alb (p<0.0001) were independent factors of NAFLD. Receiver operating characteristic (ROC) curves for NAFLD showed that cut-off values of BMI, TG, AST/ALT ratio and Alb were 22.3 or more, 108 or more, 1.30 or less and 4.2 or more, respectively.

Conclusions:
In acute stroke patients aged 40-79 years, prevalence of NAFLD on admission was high and independent metabolic factors of NAFLD were higher BMI, higher TG, lower AST/ALT ratio and higher Alb.
Abstract WP240: Urinary Biomarker of Kidney Tubular Function, Risk of Acute Kidney Injury, and Mortality in Acute Stroke Patients
Authors: Shimoyama Takashi , Sato Takahiro , Sakamoto Yuki , Nagai Koichiro , Suda Satoshi , Nishiyama Yasuhiro , Kimura Kazumi
Published: June 2021

Background and Purpose:
Urinary liver-type fatty-acid binding protein (L-FABP), which is a biomarker of kidney tubule injury, has been studied extensively and established as a risk marker of acute kidney injury (AKI) and cardiovascular disease outcomes. However, no evidence to date has indicated whether kidney tubule injury has any potential for predictor of AKI and mortality in acute stroke patients. The aim of the present study was to accurately determine the prevalence of AKI and effect on clinical outcome of acute stroke patients assessed by urinary L-FABP.

Methods:
Acute ischemic stroke and intracerebral hemorrhage patients hospitalized in the stroke care unit (SCU) within 24 h after symptom onset were prospectively investigated. AKI was defined on the basis of Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We evaluated the association among urinary L-FABP, AKI, and 3-months mortality using multivariate logistic analysis adjusted for baseline estimated glomerular filtration rate (eGFR), albuminuria, stroke risk factors, and neurological severity.

Results:
In total, 601 acute stroke patients (390 males; median age 72 years, ischemic stroke 476 cases and intracranial hemorrhage 125 cases) were enrolled to the study. AKI occurred in 32 acute stroke patients (5.3%). In the univariate analysis, high urinary L-FABP level had positive associations with AKI (25.4 μg/g Cr vs. 3.6 μg/g Cr, P<0.001) and 3 months mortality (13.4 μg/g Cr vs. 3.8 μg/g Cr, P<0.001). In the multivariate analysis, elevated urinary L-FABP level was independently associated with AKI (OR 1.015; 95% CI, 1.008-1.023, P<0.001) and 3-months mortality (OR 1.012; 95% CI, 1.001-1.023, P=0.032). Moreover, AKI also increased the risk of 3-months mortality after stroke (OR 7.053, 95% CI, 1.771-28.087, P=0.006).

Conclusion:
Biomarker of tubular dysfunction is independent predictor of AKI and mortality in acute stroke patients.
Abstract WP242: Using Systems Redesign in the Development, Implementation, and Evaluation of a Care Transitions and Hypertension (catch) Management Program for Veterans With Ischemic Stroke
Authors: Sico Jason J , Burrone Laura , Ragunton Jan-Michael , Ellimuttil Shaji , Damush Teresa , Hurd Paul
Published: June 2021

Introduction:
Systems Redesign approaches have the potential to be used to develop, implement, and evaluate the implementation of post-ischemic stroke hypertension quality improvement initiatives.

Methods:
The CAre Transitions and Hypertension (CATcH) management program is a bundled, multi-faceted, provider- and healthcare-systems level pilot-intervention designed to enhance care coordination using infrastructure routinely available within a Veterans Health Administration (VHA) medical center delivering suboptimal post-stroke hypertension care. A rapid process improvement workshop with local personnel from internal medicine, neurology, clinical pharmacy, and facility leadership. The team process mapped out the current state of post-stroke blood pressure (BP) control from the hospitalization period to outpatient follow-up, and conceptualized a future state where there was enhanced care coordination between inpatient and outpatient providers, generalists and specialists, and increased engagement of underutilized talent within clinical pharmacy and telehealth. The CATcH bundle also included a Transition in Care note to improve communication between providers. The team decided to meet weekly to determine newly identified and ongoing needs for patients. Chart review was conducted to determine healthcare utilization.

Results:
In the six-months prior to the implementation of CATcH, facility-level pass rate for BP control (i.e., obtaining BP < 140/90 mmHg) was 50% (18/36). Stroke survivors were neither discharged with telehealth for BP monitoring nor received clinical pharmacy appointments. In the six-months after CATcH implementation, facility-level pass rate for BP control was 69% (22/32). Nineteen percent were enrolled in telehealth whereas all patients received and attended at least two clinical pharmacy appointments post-discharge. All patients discharged during the intervention period were recipients of the CATcH program.

Conclusions:
A Systems Redesign approach could be used to eliminate waste and minimize variability in the process of post-stroke hypertension management while using readily available hospital infrastructure to improve hypertension care for stroke survivors.
Abstract WP245: New Definition of Hypertension and Incident Cerebral Microbleeds: A 7-Year Chinese Urban Community Study
Authors: Xia Yiwei , Wang Yi , Yang Lumeng , Wang Yiqing , Liang Xiaoniu , Zhao Qianhua , Wu Jianjun , Chu Shuguang , Liang Zonghui , Ding Hansheng , Ding Ding , Cheng Xin , Dong Qiang
Published: June 2021

Background and Purpose:
Cerebral microbleeds (CMBs) are associated with recurrent stroke, dementia and mortality in the general population. Hypertension (blood pressure over 140/90 mmHg) was thought as a crucial risk factor of CMBs in the general population. However, the cutoff for diagnosis of hypertension was lowered to blood pressure over 130/80 mmHg in the 2017 American College of Cardiology / American Heart Association (ACC/AHA) guidelines. Whether the new definition of hypertension remains a potent risk factor of CMBs is questionable. We aimed to analyze the relationship between the new definition of hypertension and incident CMBs in a 7-year longitudinal community study.

Methods:
This study is part of the Shanghai Aging Study (SAS). 159 participants without stroke or dementia (mean age, 67.7 years) underwent repeated clinical examinations and cerebral MRI at baseline (2009-2011) and follow-up (2016-2018) with a median interval of 6.9 years. CMBs at baseline and follow-up were evaluated on T2*-GRE and SWAN sequence of MRI. We classified baseline blood pressure into four categories: normal BP, elevated systolic blood pressure, stage 1 hypertension and stage 2 hypertension according to the new criteria. We assessed the association of blood pressure categories with incident CMBs by generalized linear models.

Results:
Participants with incident CMBs had higher baseline systolic blood pressure (SBP) and pulse pressure (PP) than those without incident CMBs. The difference was significant in SBP (P=0.024), and marginally significant in PP (P=0.057). Both stage 1 and stage 2 hypertension were associated with a higher risk of incident CMBs (IRR=2.77, P=0.028; IRR=3.04, P=0.011, respectively).

Conclusions:
In this 7-year longitudinal study, participants with incident CMBs had higher SBP and PP at baseline. Stage 1 and stage 2 hypertension defined by this new criterion were associated with incident CMBs.
Abstract WP247: Sex Differences in Ischemic Stroke Outcomes After Coronary Artery Bypass Graft Surgery
Authors: Atiya Marianna , Schorr Emily , Stein Laura , Dhamoon Amit S , Dhamoon Mandip S
Published: June 2021

Introduction:
Prior studies examining sex-related risk of readmission for ischemic stroke after coronary artery bypass grafting (CABG) did not adjust for preoperative co-morbidities and used small study samples that were single center or otherwise poorly generalizable. We assessed risk of readmission for ischemic stroke after CABG for females compared to males in a nationwide sample.

Methods:
The 2013 Nationwide Readmissions Database contains data on nearly 60% of all U.S. hospitalizations. We used population weighting to determine national estimates. Using all follow-up data up to 1 year after discharge from CABG hospitalization, we estimated Kaplan-Meier cumulative risk of ischemic stroke, stratified by sex, using the log-rank test for significance. We created Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for ischemic stroke readmission, with sex as the main independent variable. We ran unadjusted models and models adjusted for age, vascular risk factors, estimated severity of illness and risk of mortality, hospital characteristics, and income quartile of patient’s zip code.

Results:
An estimated 53,270 females and 147,396 males survived index CABG admission in 2013. There was a consistently elevated cumulative risk of readmission for ischemic stroke after CABG for females versus males (log-rank p value=0.0014). In the unadjusted Cox model, the HR of ischemic stroke in females vs. males was 1.35 (95% CI 1.12-1.62, p=0.0015). The elevated risk for females remained after adjusting for severity of illness (1.30 [1.08-1.56], p=0.0056) and risk of mortality (1.28 [1.07-1.54], p=0.0086). This elevated risk persisted after adjusting for multiple vascular risk factors, hospital characteristics, and income quartile of patient’s zip code (1.23 [1.02-1.48], p=0.03).

Conclusions:
In conclusion, we found a 23% increased risk of readmission for ischemic stroke up to 1 year after CABG for females compared to males in a fully adjusted model utilizing a large, contemporary, nationwide database. Further research would clarify mechanisms of this increased risk among women.
Abstract WP253: Diagnostic Evaluation and Outcome of Cerebral Fat Embolism: Single Center Retrospective Review
Authors: Taylor Breana L , Davis Arielle P , Peters Steven R , Kunze Allison , Singh Amita , Longstreth W T , Tirschwell David L , Khot Sandeep P
Published: June 2021

Introduction:
Cerebral Fat Embolism (CFE) is an underappreciated complication of trauma and orthopedic surgery whose diagnosis is mostly based on clinical suspicion. The utility of diagnostic testing is poorly defined.

Methods:
Using discharge diagnosis codes and a stroke database at a Level 1 Trauma Center, we performed a retrospective chart review of diagnostic workup and outcome for CFE from 2005 to 2019. Among those with a diagnosis of systemic fat emboli syndrome after long-bone fracture, cerebral involvement was established based on altered mental status, retinal findings, brain MRI findings or a combination of these. This report focuses on those who had MRI, all of which had findings of CFE.

Results:
Forty patients with CFE were identified, comprising 0.3% of all patients admitted with long-bone fractures. Of these patients, the average age was 39 years (SD 22), 30 (75%) were men, 28 (70%) had hypoxemia, 2 (5%) had petechial rash, and 29 (73%) were comatose, including 16 (40%) following orthopedic surgery. Brain MRI findings of CFE included scattered diffusion-restriction (60%), confluent white-matter edema (33%) and diffuse petechial hemorrhage (30%), with 27% having multiple findings of CFE. Ophthalmologic evaluation revealed exudates or hemorrhage suggestive of Purtscher-like retinopathy in 20 (91%) of 22 patients examined. Transcranial doppler microembolic signals (MES) were detected in 17 (53%) of 32 patients examined and were associated with scattered diffusion-restriction on MRI (chi square,
p
=0.01). Twelve patients (30%) died before discharge, 15 (38%) were discharged to a nursing facility, 12 (30%) to a rehabilitation facility and 1 (3%) to home. After a mean of 5.4 months, 1 patient had died, 11 had severe disability and 16 had moderate disability or better.

Conclusion:
The diagnosis of CFE is complicated by unknown sensitivity of diagnostic modalities. Nonetheless, typical MRI and ophthalmologic findings can assist in diagnosis. MES are associated with scattered infarction on MRI, suggesting active disease. The outcome of patients with CFE is highly variable, and a better understanding of this potentially devastating disease will require studies with larger numbers of cases collected in a standard fashion at multiple trauma centers.
Abstract WP256: Atrial Fibrillation Predicting Factors in Transient and Minor Stroke Patients
Authors: Muchada Lopez Marian , Pagola Jorge , Juega Jesus , Francisco-Pascual Jaume , Bustamante Alejandro , Penalba Anna , Pala Elena , Rodriguez Maite , De Lera Alonso Mercedes , Arenillas Juan F. , Cabezas Juan Antonio , Moniche Francisco , de Torres Reyes , Montaner Joan , Gonzalez- Alujas Teresa , Molina Carlos
Published: June 2021

Introduction and Purpose:
Our aim was to review the characteristics of transient ischemic attack (TIA) and minor ischemic stroke patients monitored for atrial fibrillation (AF) epidoses detection within the first 4weeks after stroke to assess AF predictors.

Materials and Methods:
TIA and minor ischemic stroke patients (nihss≤ 5) were selected from CRYPTO-AF database. CRYPTO-AF is a prospective multicentre registry of patients with cryptogenic stroke older of 55 year-old. Monitoring started within the first 72 hours from stroke symptoms onset and was prolonged for 4 weeks. Clinical, cardiographic and blood test parameters of patients included were reviewed. Fisher exact and Mann Whitney tests were used to analyze categorical and continuous data.

Results:
In our cohort of 152 transient and minor ischemic stroke patients, 55.9% were men, mean age 73.18±10.24 and median NIHSS score was 2.31(0-5). A total of 30 patients (20.3%) were diagnosed with AF in the first month of monitoring, 6 patients (5.7%) within the first 3 days, 14 patients (13.3%) between 3 days and to 2 weeks of monitoring, and 14 partientes (12.4%) between the second and the fourth week. In these transient and minor ischemic stroke patients, age (p< 0.031), left atrial volume index (p< 0.023), the appearance of isolated extrasystoles during monitoring (p< 0.021), Type B natriuretic peptide (p< 0.011) and the longitudinal strain (p< 0.019) appeared as independet precitors of AF. However in the multivariate analysis adjusted for the above variables, only left atrial strain (OR 0.89, 95% CI: 0.797-0.991, p< 0.034) independently predicts AF detection.

Conclusions:
In our serie, only the left atrial strain appeared as a indepent predictor of AF. Given the known pathophysiology of TIA and minor ischemic stroke, the description of AF predictors would help to identify those patients who would benefit from completing a longer monitoring. More studies are needed to identify these predictors.
Abstract WP262: Intravenous Thrombolysis in Acute Ischemic Stroke Patients With Infective Endocarditis
Authors: Gopal Mangala , Lakhani Sushil , Lee Vivien
Published: June 2021

Introduction:
Infective endocarditis (IE) is considered to be an absolute contraindication for intravenous tissue plasminogen activator treatment (IVtPA) in acute ischemic stroke. However during the hyperacute stroke evaluation, the exclusion of IE may be difficult.

Methods:
We reviewed consecutive patients hospitalized at our comprehensive stroke center from January 1, 2014 to March 31, 2019 with acute ischemic stroke who received IVtPA and identified patients who were diagnosed with infective endocarditis. Data was abstracted on demographics, medical history, clinical presentation, last known normal (LKN) time, initial National Institutes of Health Stroke Scale (NIHSS), neuroimaging, culture results, and 90 day modified Rankin Scale (mRS). Good functional outcome was defined as mRS ≤ 2.

Results:
Among 1022 acute ischemic stroke patients who received IVtPA, 5 patients (0.5%) were ultimately diagnosed with IE. Among the 5 patients with IE, the mean age was 53.4 years (range, 25-74) and 3 (60%) were female. The majority, 4 (80%) were white. Medical risk factors for IE were present in 3 (60%) and included intravenous drug use (1) and dialysis (2). Initial NIHSS was 4.6 (range, 1 to 8). Fever was present on initial presentation in only 1 patient (102.7 F). All patients met criteria for IVtPA and there were no protocol violations. The mean time from LKN to IVtPA was 3.0 hours (range, 1.9 to 4.4). Vascular imaging showed MCA occlusion in 4 (80%) and no occlusion in 1 (20%). One patient underwent endovascular thrombectomy with Thrombolysis in cerebral infarction scale 2A recanalization. Two patients (40%) developed hemorrhagic complications, including 1 patient who developed subarachnoid hemorrhage on Hospital Day #2 due to mycotic cerebral aneurysm. The blood culture results included MRSE (1), Streptococci viridans (2) and negative (2). TEE in all patients showed vegetations on the mitral valve. No patients had good functional outcome, and the mean 3 months mRS was 4.8 (range, 3 to 6).

Conclusions:
In a large series of acute ischemic stroke patients who received IVtPA, undiagnosed IE is rare (0.5%). Fever was not commonly present during initial evaluation. Despite affecting younger patients with initial mild deficits, patients with IE had poor functional outcomes.
Abstract WP271: The Role of Ring Finger Protein213 Variant in Patients With Intracranial Atherosclerotic Disease
Authors: Kim Hyung Jun , Bang Oh Young , Baek In-Young , Kim Jae-Hwan , Kim Ye Sel , Lee Mee So , Kim Ingyeong , Kim Gyeong-Moon
Published: June 2021

Introduction:
The
Ring Finger Protein213
(
RNF213
) gene variant is a relatively common variant in general population of East Asian countries (0.43 to 1.8%). Recently,
RNF213
is reportedly a susceptibility gene not only for moyamoya disease (MMD) but also for intracranial atherosclerosis (ICAS) in this population. However, the role of this genetic factor in patients with ICAS is unknown. We hypothesized that this variant is involved in the pathogenesis of ICAS.

Methods:
We conducted a prospective study of patients with ICAS and MMD using high-resolution MRI (HR-MRI) and
RNF213
(p.Arg4810Lys variant) gene studies. Patients were classified into intracranial atherosclerosis (ICAS) when relevant plaques existed on HR-MRI and moyamoya disease (MMD) when patients had
RNF213
variant and HR-MRI showed no plaque but characteristic features of MMD (negative remodeling and basal collaterals). We compared clinical and neuroimaging features between (a) the
RNF213
- ICAS, (b) the
RNF213
+ ICAS, and (c) MMD group.

Results:
Among 178 patients analyzed, 79 were the
RNF213
- ICAS, 37 the
RNF213
variant+ ICAS, and 62 the MMD group. Vascular risk factors were more frequently observed in ICAS than MMD patients, but there was no difference between
RNF213
- ICAS and the
RNF213
variant+ ICAS. Moreover, the site of occlusive disease was different between ICAS and MMD patients, but not between
RNF213
- ICAS and the
RNF213
variant+ ICAS. It was more distally located in
RNF213
variant+ ICAS than in MMD (p=0.012). Compared to
RNF213
- ICAS patients, tandem lesions were significantly more common in
RNF213
+ ICAS (24.1% vs. 67.6%, p<0.05), after adjusted for vascular risk factors.

Conclusions:
Patients with ICAS and the
RNF213
variant showed distinct clinical and imaging features from MMD patients. A high frequency of tandem lesions in
RNF213
+ ICAS suggest that this variant may have synergic effects in atherosclerosis which should be tested in a larger cohort.
Abstract WP275: Potential Cost Effectiveness of the Melbourne Mobile Stroke Unit
Authors: Cadilhac Dominique , Kim Joosup , Zhao Henry , Campbell Bruce , Coote Skye , Easton Damien , Smith Karen , Stephenson Michael , Bernard Steve , Desmond Patricia , Mitchell Peter , Yan Bernard , Parsons Mark , Norbury Peter , Foster Shane , Donnan Geoffrey , Davis Stephen
Published: June 2021

Background:
Mobile stroke units (MSUs) are ambulances with brain scanning capability and specialised staff. In Australia, the first MSU was launched in Melbourne, November 2017. The Melbourne MSU has two paramedics, a radiographer, a stroke neurologist and a stroke nurse specialist (5 days per week/ 8am-6pm). The MSU is co-dispatched with a standard ambulance to a patient with suspected stroke within metropolitan Melbourne (20km radius). In cases where the standard ambulance assessed the patient first and stroke is eliminated, the MSU is contacted to ‘stand-down’. The cost-effectiveness of this type of ‘pre-hospital’ service remains unclear.

Methods:
The potential cost-effectiveness of the Melbourne MSU was estimated for 2018 following the pilot period (Nov-Dec 2017). A simulation model was developed for 2018 with a) program costs: operational/finance reports, self-report program leads/senior operational staff; b) clinical processes: MSU medical records/historical data; and c) health effects of treatment taken from the literature for reperfusion therapies to patients with ischaemic stroke (i.e. benefits: additional patients treated/faster treatment). Primary outcome: incremental cost per disability adjusted life year (DALY) avoided. The comparison was to standard pre-hospital and emergency department historical ‘usual’ care. Probabilistic, multivariable uncertainty analyses with Monte Carlo (10,000) simulations and sensitivity analyses were conducted.

Results:
In 2018, the Melbourne MSU was dispatched for 1244 suspected strokes (200 operational days). Overall, 46.9 DALYs were potentially avoided (95% uncertainty interval 33.02, 82.15 DALYs). The net cost of operating the MSU was ~$US 980,000, and the incremental cost/DALY avoided was $US 20,681 compared to standard care (95% uncertainty interval $US 14,167, $US 32,214).

Conclusion:
The Melbourne MSU is a cost-effective model for stroke care based on a standard willingness-to-pay cost-effectiveness threshold (<$US 50,000 per DALY avoided). Future adaptations to the operational model may improve the cost-effectiveness of this service.
Abstract WP28: Factors Associated With Imaging and Endovascular Therapy Decisions for Mild Ischemic Stroke: An International Survey
Authors: Krementz Nastajjia A , Landman Avi , Gardener Hannah E , Rodriguez Anny D , Sur Nicole B , Marulanda-Londoño Erika , Lau Hsien Lee , Cannon Hershel , Yavagal Dileep R , Nagel Simon , Sacco Ralph L , Yan Bernard , Demchuk Andrew M , Khatri Pooja , Romano Jose , Asdaghi Negar
Published: June 2021

Background:
Approximately 1 in 7 patients with mild ischemic stroke (NIHSS ≤5) have large vessel occlusion (LVO). These patients were excluded from randomized trials of endovascular therapies (EVT). We conducted a survey to evaluate global practice patterns of EVT in mild stroke with LVO.

Methods:
International vascular stroke clinicians and interventionalists were invited to participate through professional stroke listservs. The survey consisted of 6 clinical vignettes of mild stroke patients with LVO (Table). Cases varied by NIHSS, neurological symptoms and LVO site. All had same risk factors, time from symptom onset (5h) and unremarkable head CT (high ASPECTS). Advanced imaging data was available upon request. We explored independent case and responder specific factors associated with advanced imaging request and EVT decision.

Results:
Of 492 responders, 482 had analyzable data ([median age 44 (IQR 11.25)], 78% male, 77% attending, 22% interventionalist). Participants were from USA (45%), Europe (32%), Australia (12%), Canada (6%), and Latin America (5%). EVT was offered to 48% (84% M1, 29% M2 and 19% A2). Treatment decision made without advanced imaging in 66%. In multivariable analysis, proximal occlusion (M1 vs M2 or A2, p<0.001), higher NIHSS (p<0.001) and fellow level training (vs attending; p=0.001) were positive predictors of EVT. Distal occlusion (M2 and A2) and higher age of responder were independently associated with increased advanced imaging requests. Compared to US and Australian responders, Canadians were less likely to offer EVT, while those in Europe and Latin America were more likely (p<0.05).

Conclusions:
Treatment patterns of EVT in mild stroke vary widely. More proximal occlusion, higher NIHSS, younger physician, fellow level training, and area of residence (Europe and Latin America) were key factors associated with offering EVT. These data suggest that wide equipoise exists in the current approach to this important subset of LVO stroke.
Abstract WP286: Review of Neuroimaging Prior to Transfer Acceptance and Rate of Endovascular Treatment
Authors: McCullough-Hicks Margy E , Bernier Eric , Mlynash Michael , Albers Gregory , Mijalski Sells Christina M
Published: June 2021

Background:
With the advent of extended window EVT for acute stroke (AIS), interhospital transfer is increasingly frequent; with growing demand but static resources, stroke centers need to identify patients who are most likely to benefit from transfer, as not all transferred undergo intervention. In 2018 only 57% of AIS patients transferred to Stanford for EVT were taken to the cath lab, compared to 82% accepted after telestroke consultation. For non-telestroke transfers, review of imaging prior to acceptance isn’t required but is often available. We hypothesized that the ability to review imaging prior to acceptance would improve patient selection and correlate with an increased rate of EVT.

Methods:
We analyzed data from all AIS patients accepted for transfer with the intention of EVT in 2018. Pre-acceptance images were available via emails from facilities with RAPID software, scans sent through LifeImage, or via telestroke PACS. All patients had repeat imaging on arrival to SUH.

Results:
75 of 131 patients underwent EVT (57.2%); 39.7% had pre-acceptance imaging. 65% of patients who had pre-acceptance imaging went for EVT vs 52% of those without (P=0.127). Average time from acceptance to arrival was 2h13m. 51.1% received IV tPA; tPA and time of transfer had no bearing on rate of EVT. Excluding patients who recanalized by arrival, 74% with pre-acceptance imaging went for EVT vs 59% without (P=0.113). Average infarct volume for those treated with EVT was 21.9mL vs 64.5mL in those with no EVT (p=0.04). Occlusion location included the internal carotid (31%); M1 (40%); M2 (11%); M3 (2%); and basilar (7%) arteries. Patients with ICA occlusions went for EVT most often (P<0.001). Of those who did not go for EVT, 18 of 56 (32%) were provided some form of higher level of care not available at the referring facility.

Conclusions:
Pre-acceptance imaging review was associated with a trend toward higher rates of EVT. Pre-acceptance imaging was not uniform, and utility of NCCT vs CTA vs CTP as well as assessment of collateral vessels will be presented. Telestroke evaluation may help address goals of care as well as clinical features that contribute to higher EVT rates in transfer patients.
Abstract WP296: Utilization of Advanced Imaging Paradigms Improves Patient Triage at Stroke Centers in a Stroke System of Care
Authors: Tarasaria Karan , Asad Syed Daniyal , Beland Dawn , Nouh Amre , Alberts Mark J
Published: June 2021

Background:
The 24 hour time window for endovascular therapy (EVT) in ischemic strokes due to large vessel occlusions (LVO) is a significant advance. Although many stroke systems of care have adopted a paradigm of transferring all potential EVT patients to the hub center for further evaluation, we developed an approach using advanced imaging at spoke hospitals to improve transfer triage.

Hypothesis:
Utilizing a novel algorithm combining clinical and imaging (CTA plus CT Perfusion “RAPID”) criteria at the spoke facilities results in more appropriate patient transfer decision to the CSC (hub).

Methods:
We developed and implemented a clinical and imaging screening algorithm for suspected LVO patients at our 3 PSCs and 1 CSC equipped with CTA and CTP-“RAPID” capabilities. Patients at the PSCs with NIHSS> 6 or fulfilling Stroke VAN (Hemiparesis and Visual field cut, aphasia or neglect) criteria and presenting within 24 hours from last seen normal undergo CTA plus CTP, and a decision for transfer if LVO plus core ≤50cc is met. Data including diagnosis, clinical and radiographic features, transfer status and final diagnosis of 377 patients from January 2018 to January 2019 were analyzed.

Results:
The mean age was 69 (SD 1.7) years and mean NIHSS was 11 (SD 0.79). Out of total 377 patients, 63% (n=236) were screened at PSCs and 37% (n=141) were screened at the CSC. About half (51%) of patients screened at PSCs (n=120) and 85% at the CSC (n=121) had a final diagnosis of acute ischemic stroke. Using our algorithm, 28% (n=65) patients were found to have LVO at PSCs compared to 60% (n=85) at the CSC. Only 23% (n=54) of patients were transferred to the CSC out of which 30% (n=16) underwent EVT. Among patients transferred to the CSC, 85% (n=46) had LVO, with the remaining 8 transferred for a higher level of care per. Almost half (49%) of the 116 patients screened at PSCs were stroke mimics, none of which were transferred.

Conclusion:
Using our new algorithm, 64% of screened patients were ischemic strokes and 40% had LVO’s, of whom 14% qualified for EVT. Using advanced clinical and imaging paradigms, 77% of screened patients did not require transfer. Utilization of CTP imaging at spoke PSCs is feasible and improves the accuracy and efficiency of patient transfers.
Abstract WP308: Role of Microthrombi and Vasospasm in the Development of Delayed Neurological Deficits After Subarachnoid Hemorrhage in Mice
Authors: McBride Devin W , Dienel Ari , Veettil Remya A , Matsumura Kanako , Kumar T. Peeyush , Blackburn Spiros L
Published: June 2021

Rationale:
Microthrombosis has been suggested as a major factor contributing to delayed neurological deterioration in patients after subarachnoid hemorrhage (SAH). However, experimental studies on the role of microthrombi in delayed deficits after SAH has not been investigated. Our hypothesis is that, following SAH, mice which develop delayed neurological deficits have a greater number of microthrombi than mice which do not develop delayed neurological deficits.

Methods:
SAH was induced in adult male and female C57BL/6 mice via endovascular perforation. Mice were randomly assigned into sham (n=6/sex) or SAH groups (n=22-24/sex). Neurobehavior was performed on days 1-3, 5, and 7 post-SAH using a composite neuroscore. Animals were sacrificed on the day of delayed deficits or 7 days post-SAH. Microthrombi count and vessel diameters (for vasospasm) were measured using H&E stained brain slices. All outcomes were performed and all data were analyzed by a blinded investigator.

Results:
Seventeen percent (4/24) of male mice and thirty-six percent (8/22) of female mice developed delayed deficits on days 3-5 post-SAH (Figures 1A and 1B). Those mice which developed delayed deficits had significantly more microthrombi in their brains than mice which did not develop delayed deficits; vasospasm did not correlate with delayed deficits. Additionally, female SAH mice develop delayed deficits at a higher frequency than males (Figure 1C).

Conclusions:
This work shows for the first time delayed deficits in a SAH mouse model. Further, microthrombi correlated with delayed deficits, whereas no correlation was between delayed deficits and vasospasm. The data within this study suggests that preventing microthrombi may improve functional recovery and reduce the risk of delayed deficits.
Abstract WP312: Rosiglitazone Ameliorates Tissue Plasminogen Activator-Induced Hemorrhagic Transformation After Stroke via Promoting Phagocytic Activity of Microglia
Authors: Li Yan , Zhu Ziyu , Yu Weifeng , Li Peiying
Published: June 2021

Objective:
Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may lead to lethal hemorrhagic transformation (HT) after ischemic stroke. Rosiglitazone(RSG) is one of the PPAR-γ agonists and has been reported to protect against cerebral ischemia. However, whether RSG can alleviate HT after tPA treatment still remains unknown. In this study, we sort to examine the role of RSG on tPA-induced HT.

Methods and results:
We used the murine suture middle cerebral artery occlusion (MCAO) models of stroke to investigate the therapeutic potential of RSG against tPA-induced HT. Delayed administration of tPA (10mg/kg, 2 hours after reperfusion) resulted in HT in the ischemic territory 1 day after ischemia. When RSG(6mg/kg) were intraperitoneally administered 1 hour before MCAO , HT was significantly decreased. In addition, we found the BBB disruption and tight junction damage in tPA-treated MCAO mice can be mitigated after RSG treatment. Using flow cytometry and immunostaining, we confirmed that the expression of CD206 was significantly upregulated while the expression of iNOS was down-regulated in microglia of the tPA and RSG treated MCAO mice. Simultaneously, the expression of arg-1, CD36, CD68 and TREM2 were upregulated in tPA and RSG treated stroke mice. To further address our hypothesis that RSG could exert protection against the BBB disruption
via
phenotypic change into enhanced phagocytosis activity, we intend to use the two-photon live imaging to elucidate that CX3CR1-GFP
+
microglia could phagocytose more exogenously injected rhodamine-dextran while treated with RSG and tPA compared with those treated with tPA alone. In addition, we plan to inject pH-sensitive beads through the lateral ventricle to demonstrate an increased engulfment of pH-sensitive beads after co-treatment with RSG and tPA. In vitro, phagocytic efficiency in primary microglia and BV2 cells will be verified through adding latex beads after co-administrating RSG and tPA.

Conclusions:
In conclusion, our data demonstrates that RSG treatment ameliorates HT in delayed tPA-treated stroke mice. Enhanced phagocytic activity of microglia may be responsible for the RSG afforded protection against the BBB disruption in the tPA-induced HT after stroke.
Abstract WP320: Neuronal ROCK2 Plays Important Role in Ischemic Stroke: GSK-3beta and Tau Signaling Pathways
Authors: Ahn Yong-Joo , Hwang Seo-Kyoung , Kim Nami , Lee Eun-Hye , Zhong Wenliang , Ren Xiu-Jun , Cho Su-In , Bae Jaeho , Qian Jiao , Lim Chiyeon , Kim Maya Hwewon , Kwon Ye-Rim , Koong HwaSoo , Li Ge , Yang Chengxian , Jang Dongyeol , Lee Angela Mingie , Oh Yoonji , Kim Hyeon Soo , Koh Seong-Ho , Kim Hyung-Hwan
Published: June 2021

Introduction:
The role of neuronal cell specific ROCK2 in ischemic stroke in vivo has been poorly investigated. We investigated the pharmacological effect of selective ROCK2 inhibition by selective ROCK2 inhibitor, KD025 and the genetic effect using neuronal specific ROCK2 knockout (ROCK2Eno2-/-) mice.

Methods:
Isoflurane-anesthetized littermate control (LC) and ROCK2Eno2-/- mice (20-22 g) underwent ischemia (2h middle cerebral artery occlusion (MCAO)/reperfusion (22h after 2h MCAO) injury model. An 8.0 nylon monofilament coated with a silicone was introduced into the left internal carotid artery up to the anterior cerebral artery. To assess the mechanism of ROCK2 deficiency in neuronal cells, we seeded hippocampal neuronal (HT22) cells in 6-well plates and transfected ROCK2 siRNA. Phosphorylated glycogen synthase kinase 3 beta (pGSK-3β) and Tau proteins which were involved in neuroprotection were measured by western blotting from brain lysates and neuronal cells. Infarction volume was measured by TTC staining and evaluation of behavioral was assessed by neurological deficit score (NDS) at 22h after MCAO.

Results:
In WT mice, ROCK2 inhibition by KD025 (100 mg/kg, p.o.) decreased infarct volumes and improved the NDS in ischemic stroke. ROCK activity (p-MYPT1 to MYPT1 ratio) of the brain lysates by KD025 was decreased dose-dependently in ischemic mice brain. In genetic modified mice, infarction volume (64.6 ± 10.4 vs. LC (102.3 ± 12.4), n=5) of ROCK2Eno2-/- mice was significantly decreased by 37% and the NDSs (1.8 ± 0.4 vs. LC (2.8 ± 0.5), n=5) were improved by 36% compared to the LC groups. Both pGSK-3β and Tau in HT22 cells with ROCK2 siRNA transfection and ROCK2Eno2-/- mice brain was significantly decreased compared to each respective controls.

Conclusion:
These findings indicate that neuronal ROCK2 plays important role in ischemic stroke via GSK-3β and Tau signaling pathways and inhibition of neuronal specific ROCK2 may have therapeutic benefits in ischemic stroke.
Abstract WP324: Blocking Pro-Inflammatory Platelet-Activating Factor-Receptors and Activating Cell-Survival Pathways Leads to Neuroprotection After Experimental Ischemic Stroke
Authors: Reid Madigan M , Knott Eric J , Belayev Ludmila , Khoutorova Larissa , Bazan Nicolas G
Published: June 2021

Objective:
Acute ischemic stroke triggers complex neurovascular, neuroinflammatory, and synaptic alterations. Our study tested the prediction that blocking platelet-activating factor-receptors (PAF-Rs)-induced pro-inflammatory signaling plus administering a docosahexaenoic acid (DHA) after middle cerebral artery occlusion (MCAo) would lead to sustained neurological recovery. We used two molecules: a) LAU-0901, an antagonist of the PAF-R that blocks pro-inflammatory signaling and that has shown promising efficacy in a stroke model; and b) DHA, which activates cell-survival pathways and possesses potent anti-inflammatory and neuroprotective activity in the brain.

Methods:
Sprague-Dawley rats received 2h MCAo. Behavior was evaluated at 3, 4 and 24h. Treatments: LAU-0901 (i.p. 30mg/kg, 2h after onset of stroke), DHA (i.v. 5mg/kg, 3h after onset of stroke), LAU-0901+DHA and vehicle. On day 1, following lipids were extracted: Prostaglandins (PGE2, PGF2-α, 6-keto-PGF1a), Hydroxyoctadecadienoic acid (HODE), 11-dehydro-thromboxane B2, Thromboxane B2 (TXB2), 12-hydroxyeicosatetraenoic acid (12-HETE). Lipidomic analysis was conducted using LC-ESI-MS/MS in negative ion mode and results were normalized to total sample protein.

Results:
LAU-0901 and DHA treatments alone improved behavioral scores compared to vehicle groups by 30-35%. The neuroprotective effect was enhanced using the LAU-0901+DHA, which resulted in improved behavioral scores up to 47% on day 1. Expression of 12-HETE (proinflammatory marker) was reduced by DHA, LAU, LAU+DHA (83, 67, 72%, respectively).

Conclusion:
It is remarkable that there is differential expression of eicosanoid pathways and of other lipid mediators, some of them are proinflammatory, and other are modulators of neuroinflammation in the ipsilateral stroke side. We are currently exploring the detailed molecular mechanisms involved in the combination treatment of the PAF-R antagonist, LAU-0901, plus DHA.
Abstract WP327: Modulation of Microvascular Blood Flow and Stroke Outcome via GPR39
Authors: Xu Yifan , Zhang Wenri , Barnes Anthony Paul , Federov Lev , Alkayed Nabil
Published: June 2021

Background:
Ischemic stroke is a leading cause of morbidity and mortality. Efficacy of current thrombolytic and endovascular therapies are not uniform in all patients, and depends on age, stroke severity and diabetic status. This is in part attributed to impaired microvascular reperfusion, which limits the benefit from large-vessel recanalization. Microvascular blood flow is regulated by a number of molecules including the P450 eicosanoids which are arachidonic acid-derived lipid signaling molecules whose levels are known to be altered during stroke. We have recently identified GPR39 as a dual sensor for two vasoactive P450 eicosanoids: the dilator 14,15-epoxyeicosatrienoate (EET) and constrictor 15-hydroxyeicosatetranoate (HETE). GPR39 is expressed in arteriolar vascular smooth muscle cells and peri-capillary pericytes. Thus, GPR39 is uniquely positioned to sense the balance of vasoactive eicosanoids and modulate microvascular blood flow during and following stroke. To investigate the role of GPR39 in stroke, we have generated a global GPR39 knock-out (KO) mouse via CRISPR/Cas9 deletion of the receptor’s first exon, eliminating expression of GPR39.

We tested the hypothesis that GPR39 KO mice sustain larger infarcts after transient focal cerebral ischemia compared to wild-type (WT) littermates with intact GPR39.

Methods:
A 60-min middle cerebral artery occlusion (MCAO) was induced in 3-month old male and female mice using a silicone coated filament introduced through an external carotid stump under isoflurane anesthesia. A total of 15 KO (8 males, 7 females) and 8 WT (4 males and 4 females) mice were used for the study. Brains were harvested at 24 hours of reperfusion, sliced coronally in 2-mm segments, sections stained with triphenyltetrazolium chloride (
TTC
), and infarcted areas measured after accounting for edema.

Results:
Hemispheric infarct was 44.7% ± 3.31% in male GPR39 KO mice compared to 34.7% ± 5.23% in WT male littermates (mean ± sem, p=0.07). In females, infarct size was 30.3% ± 5.58% in GPR39 KO mice compared to 33.9% ± 1.45% in WT littermates (p = 0.34).

Conclusions:
Our preliminary results suggest that GPR39 plays a sexually-dimorphic protective role in ischemic stroke, and that GPR39 may serve as a therapeutic target in stroke.