bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P601: Influenza-Like Illness as a Short-Term Risk Factor for Arterial Dissections
Authors: Buchman Rutrick Stephanie , Lansdale Kelsey , Witsch Jens , Seitz Alison P , Kamel Hooman , Parikh Neal S , Segal Alan Z , Zhang Cenai , Merkler Alexander E
Published: March 2021

Introduction:
Arterial dissections often have no known identifiable risk factor. Whether infection/inflammation may play a role in the development of arterial dissection is uncertain.

Hypothesis:
Influenza-like illness (ILI) is associated with a heightened risk of arterial dissection.

Methods:
We performed a case-crossover analysis using administrative claims data on emergency department visits and acute care hospitalizations from 2006 to 2015 in NY and 2005-2015 in FL. We used previously validated
International Classification of Diseases, Ninth Revision, Clinical Modification
codes to identify patients with ILI and arterial dissection. Arterial dissection included the composite of cervical artery dissection (carotid and vertebral), coronary artery dissection, and aortic dissection. We compared the risk of arterial dissection in successive 30-day periods after ILI versus the corresponding 30-day periods one year earlier. We used McNemar test for matched data to calculate the absolute risk increases.

Results:
We identified 2,838,178 patients with ILI. The absolute increase in arterial dissection was 0.005% (95% CI, 0.004-0.006%) in the thirty days post ILI compared with the same period one year earlier (OR 3.3, 95% CI, 2.5-4.4). The absolute increase in arterial dissection attenuated over successive 30-day periods after ILI and was no longer significant after 120 days post ILI (Figure). Our results were similar in secondary analyses evaluating cervical, coronary, and aortic dissections separately.

Conclusions:
ILI is associated with a heightened short-term risk of arterial dissection. Further studies are warranted to evaluate mechanisms of how ILI and/or related inflammation leads to a heightened risk of systemic and cerebrovascular dissections.
Abstract P619: A Non-Linear Relationship Between Time From Onset to Endovascular Therapy and Outcomes in Patients With Acute Basilar Artery Occlusion in Clinical Practice
Authors: Sang Hongfei , Yuan Junjie , Liu Shuai , Luo Weidong , Li Fengli , Song Jiaxing , Liu Hansheng , Li Linyu , Qiu Zhongming , Zi Wenjie , Yang Qingwu
Published: March 2021

Objective:
Faster time from onset to puncture (OPT) using endovascular therapy (EVT) in acute large-vessel occlusion of anterior circulation has been associated with better clinical outcomes. However, the relationship in acute basilar artery occlusion (BAO) is still not well delineated.

Methods:
We analyzed acute BAO patients receiving EVT from a nationwide registry of BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion study). The primary outcome was favorable functional outcome (defined as modified Rankin Scale score 0-3) at 90 days. Secondary outcomes included function independence (defined as modified Rankin Scale score 0-2), mortality and symptomatic intracerebral hemorrhage. The associations between OPT and outcomes were evaluated using multivariable logistic regression (OPT as a categorical variable) and restricted cubic spline regression (OPT as a continuous variable).

Results:
Among 639 eligible patients, the median age was 65 years, and median OPT was 328 mins (interquartile range, 220-490). Treatment within 4 hours were associated with higher rates of functional independence (adjusted OR, 0.60 [95% CI, 0.37-0.97] and 0.46 [95% CI, 0.22-0.97], respectively) and favorable outcome (adjusted OR, 0.63 [95% CI, 0.40-0.99] and 0.46 [95% CI, 0.24-0.96], respectively) compared with treatment within 4-8 hours and 8-12 hours. In the restricted cubic spline models, nonlinear relationships were consistently observed between OPT with favorable outcome, functional independence and mortality, with significant benefit loss throughout the first 10 hours but then a relative flat afterwards. However, the odds of symptomatic intracerebral hemorrhage did not significantly change with longer delay to EVT.

Conclusion:
Among patients with acute BAO in routine practice, earlier treatment with EVT was associated with better outcomes throughout the first 10 hours after onset, but benefit sustained unchanged afterwards. Future trials or pooled analysis of larger size BAO patients are needed to confirm these results.
Abstract P62: Older Adults With Cerebral Small Vessel Disease Show Increased Levels of Circulating Vascular Endothelial Growth Factor D
Authors: Kapoor Arunima , Gaubert Aimee , Marshall Anisa , Yew Belinda , Ho Jean K , Blanken Anna E , Dutt Shubir , Sible Isabel J , Li Yanrong , Jang Jung Y , Rodgers Kathleen , Soto Maira , Tan Alick , Nation Daniel A
Published: March 2021

Introduction:
Cerebral small vessel disease (SVD) resulting from pathological changes in cerebral microvessels is a common precursor of stroke and dementia. Progressive and insidious damage to the cerebral microvasculature may trigger angiogenic processes to promote vessel repair. However, few previous studies have explored the angiogenic response to SVD. In a cohort of older adults with early evidence of SVD, we aimed to examine circulating levels of vascular endothelial growth factor D (VEGF-D)—a secreted glycoprotein with high angiogenic and lymphangiogenic potential—which has previously been linked to heart failure, atrial fibrillation, and ischemic stroke.

Methods:
Sixty independently living older adults (mean age = 69.7 years; SD = 7.5; age range 55-90 years; 38.3% male) free of dementia or clinical stroke were recruited from the community and underwent venipuncture and brain MRI. Plasma was assayed for proangiogenic factors (VEGF-A, VEGF-C, VEGF-D, Tie-2, Flt-1). MRI changes thought to represent microvascular pathologies (white matter hyperintensities, microbleeds and lacunes) were evaluated and total SVD load was determined using a previously validated score. Multiple linear regression examined the relationship between circulating proangiogenic proteins levels and total SVD load.

Results:
Moderate/severe white matter hyperintensity burden was identified by Fazekas scale in 40.0% of participants, small lacunes were identified in 13.3% and microbleeds in 6.7%. Simple linear regression revealed a positive relationship between circulating VEGF-D and total SVD score (p = .019), which remained significant in multiple regression controlling for age, sex and Framingham stroke score (p = .017). VEGF-D was significantly positively correlated with VEGF-C (r = .37), Flt-1 (r = .31) and Tie-2 (r = .42).

Conclusions:
These findings suggest that elevated levels of circulating VEGF-D correspond with greater damage to the cerebral microvasculature in older adults with no history of clinical stroke or dementia. Additional studies are warranted to determine whether activation of systemic proangiogenic growth factors represents an early attempt to rescue the vascular endothelium and repair damage in cerebral SVD.
Abstract P633: Polygenic Susceptibility to Hypertension is Associated With Uncontrolled and Resistant Hypertension in Stroke Survivors
Authors: Acosta Julian N , Both Cameron , Szejko Natalia , Brown Stacy , Petersen Nils H , Sansing Lauren H , Sheth Kevin N , Falcone Guido J
Published: March 2021

Introduction:
Blood pressure (BP) is a highly heritable trait with numerous related genetic risk variants identified. While prior studies showed that polygenic susceptibility to hypertension (PSH) is associated with elevated BP, uncontrolled hypertension (UHTN), resistant hypertension (RHTN), and risk of stroke, its role after a cerebrovascular event remains unknown. We tested the hypothesis that PSH leads to higher BP and increased risk of UHTN and RHTN in stroke survivors.

Methods:
We conducted a nested study within the UK Biobank, including individuals of European ancestry with a prevalent ischemic or hemorrhagic stroke. To model PSH, we created polygenic risk scores (PRS) for systolic, diastolic, and pulse BP using 732 previously discovered loci. We divided the PRS into quintiles and used linear and logistic regression to test whether higher PSH led to higher observed BP as well as increased risk of UHTN (SBP >140 mmHg or DBP >90 mmHg) and RHTN (UHTN despite being on >=3 antihypertensive drugs) in stroke survivors.

Results:
Of the 502,536 participants enrolled in the UK Biobank, 5,815 (1.2%) with a prevalent stroke at enrollment were included. We found the following results across quintiles 1 through 5 of the systolic BP-based PRS: mean systolic BP 138.4, 140.6, 141.8, 142.9 and 145.8 mmHg (unadjusted p<0.0001, Figure’s left panel); risk of UHTN 46%, 51%, 52%, 56% and 59% (unadjusted p<0.0001, Figure’s center panel); and risk of RHTN 1.9%, 3.8%, 4.7%, 5.8% and 6.7% (unadjusted p<0.0001, Figure’s right panel). We obtained similar results when both evaluating diastolic and pulse BP-based PRSs and using adjusted multivariable models (all p<0.0001).

Conclusion:
PSH is associated with observed BP and the risk of UHTN and RHTN in stroke survivors. Follow up research should evaluate whether precision medicine strategies based on BP-related genetic information can help identify patients that could benefit from aggressive diagnostic and/or therapeutic interventions.
Abstract P651: Should I Stay or Go: Seeking Stroke Care During Covid-19
Authors: Libby Kathyrn J , Couts Linda , Schoenheit-Scott Paige , Olson-Mack Lindsay L , Kenner Brininger Amelia , Reeling Carol A , Davis Cecile , Sundby Christine , Perrinez Emily , Rockwell Jean M , Burley Jessica , Bueno Olena , Januszewicz Lourdes , Kenny Luisa J , Nabulsi Mohammed , McGurk Penny , Calara Robin M
Published: March 2021

Introduction:
On March 16, 2020 San Diego County implemented a stay at home order in response to COVID-19 pandemic; followed by the state of California instituting a shelter in place order. Locally, San Diego County’s stroke receiving centers (SRC) determined a 30% drop in stroke code activations between March-April 2020 compared to the same time in 2019 indicating a possible delay in seeking care. Utilizing discharge data, we sought to understand the impact of the stay at home order on the timeliness of seeking care.

Hypothesis:
We hypothesized an increase in last known normal (LKN) to hospital arrival time and a decrease in alteplase (tPA) and endovascular therapy (EVT) treatment rates between March 16-June 30 2020 compared to March 16-June 30 2019.

Methods:
AIS patients presenting to one of 16 SRC in San Diego County between March 16-June 30 in 2019 and 2020, discharged from the hospital or treated in the ED and transferred to another facility were included. Patients arriving as transfers from another facility were excluded.

Results:
In 2019, of 1,342 AIS cases LKN time was recorded for 85.6% of cases; of 1,092 cases in 2020 86.4% of cases had a LKN. Average LKN to arrival was 20.5 hours in 2019 and 32.4 hours in 2020 (p = .001, 95% CI [4.79, 18.93]). In 2019, 209 (15.6%) received tPA and 91 (6.8%) had EVT. In 2020, 144 (13.2%) received tPA and 75 (6.9%) had EVT. Odds that a case in 2019 received tPA was 1.21 times that of cases in 2020 (p=.09). Odds that a case in 2019 had EVT was .99 times that of cases in 2020 (p=.93).

Conclusion:
Ischemic stroke patients arriving between March 16-June 30, 2020 had a longer LKN to arrival time compared to the same time frame in 2019. The longer time to arrival may have been due to patients waiting longer to seek care, as anecdotal information from patients eluded to. The odds of receiving tPA or EVT treatment in 2020 compared to 2019 were not statistically significant. This may be due to patients experiencing acute symptoms accessing healthcare at the same rate in 2020 as 2019. Analysis of percent of patients arriving within 4 hours of LKN and average NIHSS are important next steps to determine this. Regardless, during a time of community crisis, it is important to broadcast community messaging focusing on the importance of seeking emergency care for stroke-like symptoms.
Abstract P661: Atheromatous Disease of the Parent Artery is Common in Patients With Lacunar Infarcts
Authors: Yang Dixon , Cutting Shawna M , Raz Eytan , Torres Jose L , Mac Grory Brian C , Scher Erica , Pirooz Sahnaz , De Havenon Adam H , Ishida Koto , Furie Karen L , Gutierrez Jose , Elkind Mitchell S , Yaghi Shadi
Published: March 2021

Background:
Perforator disease caused by parent artery atheromatous disease is one of the mechanisms implicated in the pathogenesis of lacunar infarcts, but there is limited data on its prevalence. We sought to determine the prevalence of parent vessel atheromatous disease in patients with lacunar infarcts.

Methods:
This is a retrospective study of consecutive patients with lacunar strokes admitted to NYU Langone Medical Center and Brown University from 2017-2019. Lacunar infarct was defined as subcortical infarct <1.5cm on CT or <2cm on diffusion-weighted imaging without significant stenosis (>50%) in the parent vessel and no cardioembolic source. Non-invasive imaging (CTA or MRA) was reviewed by a neuroradiologist or a vascular neurologist to determine the presence or absence of stenosis (< 50%) or luminal irregularity without stenosis in the stem artery segment at the location of the perforator corresponding to the infarct. Patients were divided into two groups: luminal irregularity/stenosis vs. none. We compared clinical and radiographic characteristics and rates of neurological deterioration between the two groups.

Results:
Among 208 patients with lacunar infarcts (mean age 68.9±11.9 years, 40.9% women, 61.1% White, 13.9% Black, and 12.5% Hispanic), 42 (20.2%) had luminal stenosis and 90 (43.3%) had luminal irregularity without stenosis. Baseline characteristics and prevalence of risk factors were similar between the two groups. Patients with luminal irregularity/stenosis had longer median infarct diameter (10.6 mm vs 8.7 mm, p=0.007). Other imaging variables such as the presence of prior lacunar infarcts and white matter disease burden assessed by Fazekas Score were not significantly different between the two groups. The rate of any neurological deterioration after admission was similar between the two groups (22.7% vs. 15.8%, p=0.283).

Conclusion:
In this multi-ethnic population, nearly two-thirds of patients with a lacunar infarct were found to have luminal irregularity or stenosis in the parent artery corresponding to the infarct, implying a potential atherosclerotic mechanism. Future studies are needed using advanced imaging of the stem artery to define plaque characteristics which may help determine the underlying mechanism.
Abstract P67: Role of Genetic Variants in Predicting Cognitive Outcomes Following Small Vessel Ischemic Stroke
Authors: Kam Wayneho , Goldstein Larry B , McConnell Alec , Al-Khalidi Hussein , Bennett Ellen , Colton Carol , Bushnell Cheryl D , Koltai Deborah , El Husseini Nada K
Published: March 2021

Background:
About 20% of patients with small vessel ischemic stroke (SVS) have cognitive impairment; however, the role of genetic factors in predicting cognitive outcomes following SVS has not been fully explored. APOE and ABCC9 have been associated with Alzheimer’s disease and hippocampal sclerosis respectively and play an important role in the neurovascular unit. We evaluated whether allelic variants in these genes influence cognitive outcomes following SVS.

Methods:
We conducted a retrospective analysis of a prospective cohort of patients enrolled in the ASA-Bugher Small Vessel Intracranial Disease Whole Genome Association Studies. Patients with SVS were categorized by APOE (presence or absence of ε4 allele) and ABCC9 SNP rs704180 (presence or absence of A allele) status. The primary outcomes were total score on the short form of the MoCA, which assesses global cognition, and time to complete Trails B, which is a measure of executive function that can be affected by stroke. Linear regression analyses were performed using the genetic exposures of interest, adjusting for age, education, sex, race/ethnicity, NIHSS score, burden of white matter disease (WMD; using the CHS validated score 0-9), and time between stroke and the cognitive assessment.

Results:
The sample included 145 patients who had SVS and available APOE and ABCC9 data. Among this cohort, 51.4% were men and 27.6% African American. The median age of the study participants was 63.4 years, the median years of education was 12, the median NIHSS was 2, and the median WMD burden score was 2. The mean time between stroke and the cognitive assessment was 75 days. The APOE ε4 allele was present in 35.0% and ABCC9 A allele in 74.8%. The presence of APOE ε4 allele was not associated with post-stroke MoCA scores (p=0.31) or Trails B (p=0.86). ABCC9 A allele was also not associated with post-stroke MoCA scores (p=0.34) or Trails B (p=0.31). Older age, higher NIHSS score, and greater burden of WMD were independently associated with longer times to complete Trails B (p<0.0001), but not with the MoCA score.

Conclusion:
Following SVS, several patient characteristics, including age, stroke severity, and WMD burden, rather than their APOE and ABCC9 allelic statuses, were associated with post-stroke measures of executive function.
Abstract P670: Obesity and Mortality After the First Ischemic Stroke: Is Obesity Paradox Real?
Authors: Chaudhary Durgesh , Khan Ayesha , Gupta Mudit , Hu Yirui , Li Jiang , Abedi Vida , Zand Ramin
Published: March 2021

Introduction:
Obesity is an established risk factor for ischemic stroke but the association of increased body mass index (BMI) with survival after ischemic stroke remains controversial. Many studies have shown that increased BMI has a “protective” effect on survival after stroke while other studies have debunked the obesity paradox. This study aimed at examining the relationship between BMI and all-cause mortality at one year in first-time ischemic stroke patients using data extracted from different resources including electronic health records.

Methods:
We analyzed consecutive ischemic stroke patients captured in the Geisinger NeuroScience Ischemic Stroke (GNSIS) database. Survival in first-time ischemic stroke patients was analyzed using Kaplan-Meier estimator, stratified by different BMI categories. The predictors of mortality at one-year were assessed using a multivariate Cox proportional hazards model.

Results:
Among 6,703 first-time adult ischemic stroke patients, mean age was 70.2 ±13.5 years and 52% were men. Of these patients, 24% patients were non-overweight (BMI < 25), 34% were overweight (BMI 25-29.9) and 41% were obese (BMI ≥ 30). One-year survival probability was significantly higher in overweight patients (87%, 95% CI: [85.6 - 88.4], p<0.001) and obese patients (89.5%, 95% CI: [88.4 - 90.7], p<0.001) compared to non-overweight patients (78.1%, 95% CI: [76.0 - 80.1]). In multivariate analysis, one-year mortality was significantly lower in overweight and obese patients (overweight patients- HR = 0.61 [95% CI, 0.52 - 0.72]; obese patients- HR = 0.56 [95% CI, 0.48 - 0.67]). Other significant predictors of one-year mortality were age at the ischemic stroke event (HR = 1.04 [95% CI, 1.03 - 1.04]), history of neoplasm (HR = 1.59 [95% CI, 1.38 - 1.85]), atrial fibrillation or flutter (HR = 1.26 [95% CI, 1.09 - 1.46]), heart failure (HR = 1.68 [95% CI, 1.42 - 1.98]), diabetes mellitus (HR = 1.27 [95% CI, 1.1 - 1.47]), rheumatic disease (HR = 1.37 [95% CI, 1.05 - 1.78]) and myocardial infarction ((HR = 1.23 [95% CI, 1.02 - 1.48]).

Conclusion:
Our results support the obesity paradox in ischemic stroke patients as shown by a significantly decreased hazard ratio for one-year mortality among overweight and obese patients in comparison to non-overweight patients.
Abstract P686: Ischemic Stroke in Reversible Cerebral Vasoconstriction Syndrome
Authors: Garg Aayushi , Elmashala Amjad , Ortega Santiago
Published: March 2021

Introduction:
Ischemic stroke is the cause for major morbidity and mortality in reversible cerebral vasoconstriction syndrome (RCVS). While there is evidence to suggest that ischemic stroke in RCVS is associated with proximal vasoconstriction, it is still unclear why some patients develop ischemic lesions. The aim of this study was to evaluate the risk factors and outcomes of ischemic stroke in RCVS.

Methods:
We utilized the Nationwide Readmissions Database 2016-2017 to identify all hospitalizations with the discharge diagnosis of RCVS. Occurrence of acute ischemic stroke was identified. Hospitalizations with the diagnosis of hemorrhagic stroke were excluded. Survey design methods were used to generate national estimates. Independent predictors of ischemic stroke were analyzed using multivariable logistic regression analysis with results expressed as odds ratio (OR) and 95% confidence intervals (CI).

Results:
Among the total 1,065 hospitalizations for RCVS during the study period (mean±SD age: 49.0±16.7 years, female 69.7%), 267 (25.1%) had occurrence of acute ischemic stroke. Patients with ischemic stroke were more likely to have history of hypertension (OR 2.33, 95% CI 1.51-3.60), diabetes (OR 1.81, 95% CI 1.11-2.98), and tobacco use (OR 1.64, 95% CI 1.16-2.33) and less likely to have a history of migraine (OR 0.56, 95% CI 0.35-0.90). Patients with stroke were more likely to develop cerebral edema. They also had longer hospital stay, higher hospital charges, and lower likelihood of being discharged to home or inpatient rehabilitation facility. They had higher in-hospital mortality rate, the difference was however not statistically significant.

Conclusion:
In conclusion, ischemic stroke affects nearly 25% of patients with RCVS and is associated with an increased rate of other neurologic complications and worse functional outcomes. Patients with traditional cerebrovascular risk factors might have a higher predisposition for developing the ischemic lesions.
Abstract P696: Organic Sleep Disorders Are Linked With Stroke- A Nationwide Population Study
Authors: Patel Urvish K , Patel Priyadarshee , Dondapati Lavanya , Abdulqader Mohammed Ali , Bhriguvanshi Arpita , Khan Simin , Spataro William , Napier Richard , Urhoghide Eseosa , Martin Mehwish , Lunagariya Abhishek
Published: March 2021

Objective:
Primary aim of this study is to identify prevalence of organic sleep disorders (OSDs) [REM sleep behaviour disorder (REMSBD), hypersomnia, parasomonia, insomnia, circadian rhythm] and compare prevalence of stroke [acute ischemic stroke (AIS), transient ischemic attack (TIA), intracerebral hemorrhage (ICeH), subarachnoid hemorrhage (SAH)] amongst OSDs. Secondary aim of the study is to evaluate the association between OSDs and stroke subtypes.

Methods:
A retrospective study was performed using National Inpatient Sample [2016-2017] for adult hospitalizations. We extracted a cohort of diagnoses of OSDs amongst which diagnoses of stroke were identified using ICD 10 code. Weighted analysis using chi-square test and mix-effects multivariable survey logistic regression was performed to evaluate the prevalence and odds of stroke amongst OSDs.

Results:
Out of 58,259,589 US hospitalizations, 2715 (0.00005%), 4120 (0.01%), 3420 (0.01%), 1,301,209 (2.23%) and 24870 (0.04%) had REMSBD, parasomnia, circadian rhythm, insomnia, and hypersomnia, respectively. Prevalence of AIS was higher in REMSBD [3.1 vs 2.1% p<.0004], hypersomnia [2.7 vs 2.1% p<.0001], parasomnia [2.6 vs 2.1% p=.0714], and circadian rhythm [2.8 vs 2.1% p=.0102]. Prevalence of TIA was higher in REMSBD [1.3 vs 0.6% p<.0001], parasomnia [1.3 vs 0.6% p<.0001] and hypersomnia [0.7 vs 0.5% p=.0188]. Prevalence of ICeH was higher in hypersomnia [0.5 vs 0.4% p=.0043], parasomnia [0.5 vs 0.4% p=.3239], and circadian rhythm [1.3 vs 0.4% p=.0188]. Prevalence of SAH was higher in circadian rhythm [0.6 vs 0.1% p<.0001]. In analysis, patients with parasomnia had higher odds of TIA [aOR 2.8; 95%CI 1.02-7.5] and a weak association with ICeH [1.9 (0.5-7.9)]. Circadian rhythm OSD had 214% [3.1 (1.6-6.1)] and 310% [4.1 (1.5-11.0)] higher risk of ICeH and SAH, respectively and a weak association with AIS [1.3 (0.8-2.1)]. Hypersomnia had a weak association with AIS [1.2 (1.0-1.4)], TIA [1.1 (0.8-1.6)] and ICeH [1.4 (0.9-2.0)]. REMSBD had a weak association with AIS [3.6 (0.8-15.4)].

Conclusion:
Our study shows organic sleep disorders (OSDs) are associated with strokes. Even Though the extent of association varies in each OSDs, early identification and prompt management of OSDs may mitigate the risk of stroke.
Abstract P702: How Many Cryptogenic Stroke Patients Should Be Candidates for Patent Foramen Ovale Closure?
Authors: Mitsumura Hidetaka , Kitagawa Tomomichi , Tanabe Maki , Sato Takeo , Takatsu Hiroki , Komatsu Teppei , Sakuta Kenichi , Sakai Kenichiro , Umehara Tadashi , Omoto Shusaku , Murakami Hidetomo , Iguchi Yasuyuki
Published: March 2021

Background and Purpose:
Recent several studies demonstrated that percutaneous patent foramen ovale (PFO) closure reduced the risk of stroke recurrence for patients with cryptogenic stroke (CS) and PFO. Our aim of this retrospective study is to survey the frequency of CS, which can be an indication of PFO closure.

Methods:
Subjects were consecutive stroke patients with symptomatic ischemic lesion detected by magnetic resonance imaging. Of them, CS were extracted according to exclusion of small-vessel collusion, large-artery atherosclerosis, cardioembolism, definite case of aortogenic embolism, and distinctive causeof ischemic stroke such as arterial dissection, hypercoagulable state and so on. After that, we selected patients in accordance with clinical guideline of PFO closure recommended by the Japanese Stroke Association (Figure). We analyzed the prevalence of CS with right-to-left shunt (RLS) as a good and recommended candidates for PFO closure.

Results:
Among 1,374 ischemic stroke patients from October 2012 to September 2019
,
CS were 240 patients (83 females, mean age of 66 years, 17% of subjects). Of them, 100 patients (42%) had RLS (PFO; 65, atrial septal defect; 1, pulmonary arteriovenous fistula; 1, positive on transcranial Doppler (not performed in TEE) including 21 cases of definite of paradoxical embolism. In 65 patients of CS with PFO, 30 patients younger than 60 years (13% of CS) were good candidates for PFO closure. Moreover, 22 of 1,374 (1.6%) patients who were recommended candidates had one or more high risk factors of PFO, for example large shunt, atrial septal aneurysm, and the presence of shunt at rest (Figure).

Conclusions:
In our preliminary survey, 2% of acute ischemic stroke should be PFO closure candidates.
Abstract P71: Global Blood-Brain Barrier Disruption After Acute Stroke
Authors: Leigh Richard , Kern Kyle , Wright Clinton B
Published: March 2021

Background:
Acute ischemia is known to cause local disruption of the blood-brain barrier (BBB), but studies have also shown that BBB disruption can be detected remote from the acute lesion. We sought to test a whole brain measurement of BBB disruption.

Methods:
This is a retrospective analysis of a deidentified dataset of stroke patients who did not undergo thrombolysis or thrombectomy and had an MRI performed with perfusion weighted imaging (PWI) 4-24 hours after symptom onset. We used PWI source images to identify voxels that demonstrated gadolinium leakage during the acquisition. BBB disruption was defined as a >1% change in signal due to leakage compared with normal tissue. Voxels that did not demonstrate adequate bolus tracking where excluded as noise. This yielded a whole brain average of voxels demonstrating BBB disruption that was not due to noise (wbBBB). We examined age, sex, NIHSS, Fazekas score, and time from onset as predictors of wbBBB using linear regression (continuous variables) and logistic regression (binary variables).

Results:
The 432 patients included in the analysis had a median age of 72 and 50% were women (mean NIHSS=6). wbBBB was highly correlated with age (p<0.001); figure 1A shows the 95% confidence intervals for the linear fit between age and wbBBB. There was no significant association with sex (p=0.143), NIHSS (p=0.097), or time from onset (p=0.149). wbBBB was associated with Fazekas score of the deep white matter (p<0.001) and the periventricular white matter (p<0.001). In multivariable analysis, age (p=0.011) and deep WMH (p=0.027), but not periventricular WMH (p=0.725), were independently associated with wbBBB. Figure 1B shows a boxplot of how wbBBB increases with increasing Fazekas score in the deep white matter.

Conclusions:
Global BBB disruption measured in stroke patients increased with increasing age and cerebral small vessel disease. It remains to be determined if these findings represent an acute exacerbation of a chronic process.
Abstract P712: Metabolic Syndrome is Associated With Risk of Ischemic Stroke in Patients With Non-Valvular Atrial Fibrillation- A National Estimate
Authors: Patel Urvish K , Patel Priyadarshee , Kaur Vikram Preet , Abdulqader Mohammed Ali , Laller Srishti , Datta Abhigyan , Sheriff Faisal , Rapisura Mark , Singh Gurinder , Martin Mehwish , Urhoghide Eseosa , Santos Roberta , Lunagariya Abhishek
Published: March 2021

Objective:
Primary objective of this study is to find prevalence of metabolic syndrome (MetS) in patients with acute ischemic stroke (AIS) amongst non-valvular atrial fibrillation (NVAF). Secondary aim of this study is to identify the independent components of MetS (obesity, diabetes, hypertension, high TG, low HDL), those predict AIS and compare with CHA
2
DS
2
VASc score (CHF, HTN, age>75, DM, history of stroke/TIA/thromboembolism, history of vascular disease, sex: female) amongst NVAF.

Methods:
A cross-sectional study was performed to identify cohort of adult hospitalization with secondary diagnosis of NVAF from Nationwide Inpatient Sample of 2008-2017. From patients with NVAF, primary hospitalization for AIS and secondary diagnosis of MetS, its components, and components of CHA
2
DS
2
VASc score were identified using ICD 9 & 10 codes. Weighed analysis using multivariable survey logistic regression was performed to evaluate the predictive potential of MetS and its components as well as to compare them with CHA2DS2VASc for AIS.

Results:
Amongst 33,462,134 hospitalizations with NVAF, 2.9% were due to AIS. Amongst AIS hospitalizations prevalence of MetS was 0.16% (vs 0.20%) [obesity (8.4 vs 13.7%), DM (31.6 vs 34.1%), HTN (84.3 vs 75.9%), high TG (0.4 vs 0.2%), low HDL (0.02 vs 0.02%)] in comparison to non-AIS. (p<0.001) In regression analysis, patients with MetS [aOR 1.16 (95%CI 1.04-1.30)] and its component DM [1.3 (1.3-1.4)], HTN [2.2 (2.1-2.3)], high TG [1.8 (1.7-2.0)], low HDL [1.02 (0.7-1.4) weak significant] had higher risk of AIS. Amongst CHA
2
DS
2
VASc components besides HTN and DM, history of stroke/TIA, history of vasc. disease, female and age 65-74 and >75 had higher odds of AIS
(Table 1)
.

Conclusion:
MetS and its components high TG and low HDL independently predict a high risk of AIS. Future study would evaluate whether adding of high TG and low HDL in CHA
2
DS
2
VASc score and starting anticoagulants amongst patients MetS may mitigate the risk of AIS.
Abstract P714: Knowledge of Stroke Warning Signs and Risk Factors in Minnesota Adults
Authors: Hadidi Niloufar N , Tierney Meghan K , Claeys Jane , Gurvich Olga V
Published: March 2021

Background:
Global Burden of Disease identified stroke as the second leading cause of death worldwide after ischemic heart disease. Many stroke risk factors are preventable with lifestyle changes. A better understanding of the relationship between demographics and knowledge of stroke risk factors and warning signs may help in identifying target populations for preventative stroke education.

Purpose:
This study aimed to explore 1)knowledge of stroke risk factors and warning signs among Minnesota adults, 2)association between knowledge of risk factors and presence of risk factors and 3)association between the knowledge of warning signs and family history of stroke.

Methods:
A cross-sectional survey of 207 consenting adults who completed open-ended questionnaires on identifying stroke risk factors and warning signs per American Stroke Association (ASA) was used. Self-reported demographics, medical/family history and lifestyle behaviors data were combined with measured height, weight and blood pressure to provide an individual stroke risk score per the ASA Stroke Risk Score.

Results:
Most participants(90.3%) correctly identified at least one stroke warning sign, but <1% identified all warning signs (FAST+Walking+Vision). 58.9% identified ≥3 stroke risk factors while only 2.4% identified 6 risk factors. Of the highest ranked stroke risk factors(hypertension, smoking, diabetes, diet, obesity, exercise, age, gender, atrial fibrillation), hypertension and obesity were the most named, correctly identified by 64.3% and 53.1% respectively. Females were slightly more knowledgeable of risk factors(63.9% females vs. 51.8% males) and warning signs(62.3% females vs. 58.8% males). No statistically significant associations were observed between knowledge of risk factors and presence of them, or between family history of stroke and knowledge of stroke warning signs.

Conclusion:
The findings of this study identified the need for public education of stroke risk factors and warning signs as a critical first step in behavior change. Gender differences in knowledge was slightly different. Other demographic differences was not identified due to study sample homogeneity. Additional efforts should be made to increase sample diversity in future studies.
Abstract P718: The Relationship Between Abdominal Obesity and Quality of Life and Recurrence After First-Ever Ischaemic Stroke: A Hospital-Based Prospective Study
Authors: Wang Ju , Zhang Jing , Qiang Yao , Shu Ting , Zhou Muke , Zhu Cairong
Published: March 2021

Background and Objective:
Both quality of life (Qol) and stroke recurrence are prognostic indicators for stroke survivor in different aspects. Studies have analyzed Qol and survival outcomes at the same time were sparse. And the comprehensive impact of abdominal obesity on Qol and recurrence remains unclear. The purpose of this study was to explore the comprehensive effect of abdominal obesity on the Qol and recurrence among ischaemic stroke survivors in China.

Methods:
Baseline information was collected with face-to-face interviews, Qol and obesity status for each patient were obtained through every 3 months via telephone follow-up, from 2010 to 2018. Qol was evaluated with the 12-item Short-Form Health Survey (SF-12), consists of physical component summary scores (PCS) and mental component summary scores (MCS). WC (waist circumference) were 2 categories (normal WC and abdominal obesity), according to Chinese-specific criteria. After establishing the linear mixed effect model and spline-PH model by R software, joint model model was used to explore the comprehensive effect of abdominal obesity on the Qol and recurrence.

Results:
According to the inclusion and exclusion criteria, 894 subjects were included in the study. At baseline, subjects were aged 17 to 89 years, and 487(54.47%) were abdominal obesity. During the study period, 195 (21.81%) patients recurred. Controlling for comorbidity and socio-demographic characteristics, abdominal obesity have similar effect on Qol and recurrence (overall effect: 0.162; HR: 1.176; 95%CI: 0.877~1.579). Similar results were obtained, when analysis of both PCS and recurrence (overall effect: 0.141; HR: 1.151, 95%CI: 0.857~1.547). As for the comprehensive effect on MCS and recurrence, abdominal obesity got higher risk than normal WC (overall effect: 1.280; HR: 3.597, 95%CI: 1.555~8.317).

Conclusion:
abdominal obesity increased comprehensive risk of MCS and recurrence, and abdominal obesity may have greater impact on the MCS of stroke survivors than PCS.
Abstract P72: The Obesity Paradox: Association Between Body Mass Index (BMI) and Disability After Stroke
Authors: Helms Brianna R
Published: March 2021

Background:
Present rise in the incidence of obesity has led to several opposing reports regarding the association between obesity and stroke outcomes. The objective of this study was to investigate a proposed paradoxical relationship between body mass index (BMI) and functional status in ischemic stroke patients at time of hospital discharge.

Methods:
Saint Francis Hospital Comprehensive Stroke Center patient databases were utilized in identifying 948 patients eligible for retrospective chart review over a period of 15 months. Subjects were divided into 4 groups according to BMI: underweight (BMI < 18.5 kg/m
2
), normal weight (BMI 18.5-24.9 kg/m
2
), overweight (BMI 25.0-29.9 kg/m
2
), and obese (BMI ≥ 30.0 kg/m
2
). Covariates, such as age, gender, prior to event modified Rankin scale (mRS), stroke recurrence, and smoking, were considered. Functional status and disability of stroke patients was scored via mRS at hospital discharge. Ordered logistic regression, Pearson’s chi-squared test, and Pearson’s r correlation were used for analysis to assess the association of BMI and functional status in ischemic strokes.

Results:
Of 948 eligible subjects, 49.9% were female and mean (SD) age was 69.4 (14.5) years. According to BMI, 22 (2.3%) were underweight, 247 (26.1%) normal weight, 319 (33.7%) overweight, and 360 (37.9%) obese. After adjusting for covariates, ischemic stroke patients with an increased BMI (OR, 0.98; 95% CI, 0.96-0.99) were not associated with increased disability risk upon discharge. Obese (16.2%) and overweight (14.1%) patients discharged with a mRS of 0 (back to baseline) or 1 more frequently compared to normal weight (6.1%) and underweight (0.21%) patients (
P
<0.001). Furthermore, an inverse association between BMI status and disability was significantly evident (
r
= -0.17,
P
< 0.001).

Conclusion:
Obese and overweight stroke patients discharge with a lower risk of disability than normal weight and underweight patients, supporting the existence of the “obesity paradox” in stroke. An inverse association between obesity status and functional outcome was identified and remained significant regardless of covariates.
Abstract P725: Cerebral Endothelial Cell Derived Exosomes Promote Neurogenesis and Improve Cognitive Function in Aged Diabetic Rats
Authors: Zhang Li , Li Chao , Wang Chunyang , Huang Rui , Chopp Michael , Zhang Zheng Gang
Published: March 2021

Introduction:
Middle age and elderly patients with type II diabetes mellitus (DM) are at high risk to develop cognitive decline and dementia. Reduction of hippocampal neurogenesis is highly associated with impairment of cognitive function. Exosomes are small extracellular vesicles that play an important role in intercelluar communication by transferring proteins, lipids, and genomic materials including microRNAs between cells. In the present study, we tested the hypothesis that exosomes derived from healthy cerebral endothelial cells promote hippocampal neurogenesis and ameliorate cognitive impairment in aged DM rats.

Methods:
DM was induced in middle aged rats (13 month) by co-administration of nicotinamide and streptozotocin (NTM-STZ). Two months (2M) after NTM-STZ injection, rats with confirmed hyperglycemia were treated with exosomes derived from cerebral endothelial cells of healthy young-adult rats (CEC-Exo, 1x10
11
particles, IV, n=10) or saline (n=10), twice a week for 8 consecutive weeks. Bromodeoxyuridine (BrdU, IP) was administered daily for 7 days starting at 2M after NTM-STZ injection.

Results:
Compared with DM rats treated with saline, treatment of DM rats with CEC-Exo significantly (p<0.05) improved cognitive functions measured by Morris water maze (47±4% vs 40±5% of time spent in the correct quadrant), odor recognition test (56±6% vs 48±7% time spent on new odor), and the social interaction test (67±9% vs 54±14% interaction time with new rat). In addition, CEC-Exo robustly increased number of BrdU
+
cells by 60% and DCX
+
cells by 45% in the subgranular zone of the dentate gyrus compared with saline. Moreover, DCX
+
cells significantly increased their branch numbers by 54% and lengths by 51% in DM rats treated with CEC-Exo, suggesting that CEC-Exo promote DCX
+
neuroblasts maturation. Concurrently, CEC-Exo treatment significantly reduced numbers of vessels with fibrin deposition (8±3/mm
2
vs 18±7/mm
2
in saline) and extravascular leakage (3±2/mm
2
vs 7±3/mm
2
in saline) in the hippocampus.

Conclusion:
Treatment with CEC-Exo improves cognitive function in aged DM rats and augments neurogenesis and reduction of vascular thrombosis in the hippocampus, which in concert likely contribute the therapeutic effect of CEC-Exo.
Abstract P728: Promoting Neuron Survival After Ischemic Stroke via Restoring Astrocytic Endoplasmic Reticulum Function and Glucose Metabolism
Authors: Liu Ruijia , Jalali Shayan , Sun Dandan , Zhang Zhongling , Begum Gulnaz
Published: March 2021

Stroke-induced reactive astrocytes exhibit abnormal functions and contribute to neurodegeneration. Thus, restoring normal homeostatic astrocyte functions is important for neuroprotection. Overstimulation of Na
+
/H
+
exchanger 1 (NHE1) activity after stroke triggers reactive astrocyte formation, which displays abnormal functions. We have shown that targeted deletion of
Nhe1
in astrocytes leads to inhibition of reactive astrocytes, reduced infarct volume, and improved neurological function after ischemic stroke. In the present study, we investigated ischemic stroke-mediated endoplasmic reticulum (ER) stress and unfolded protein response (UPR) and its impact on cellular reparative functions. Astrocyte specific deletion of
Nhe1
in

Gfap-Cre
ERT2+/-
;Nhe1
f/f

mice (
Nhe1
Astro-KO) was induced by tamoxifen (Tam) treatment.

Gfap-Cre
ERT2-
/-
;Nhe1
f/f

mice treated with Tam served as wild-type (WT) controls. In transient middle cerebral artery occlusion (tMCAO) model, ischemic stroke triggered a significant increase in expression of ER stress marker proteins ATF4 and CHOP at 24 h reperfusion (Rp) in WT ischemic brains (p< 0.05), no such elevation was detected in
Nhe1
Astro-KO ischemic brains. Immunocytochemical analysis revealed abundant ER chaperone protein GRP78 expression in non-ischemic cortical neurons (NeuN
+
) of WT brains, but it was reduced by ~ 70% at 48 h Rp (p < 0.001). In contrast,
Nhe1
Astro-KO brains preserved ER chaperone protein GRP78 in NeuN
+
cells in the ischemic cortex, and their adjacent GFAP
+
astrocytes showed ~40% increased GRP78 expression compared to WT. These polarized astrocytes with elevated GRP78 expression may provide neuroprotective support. Dysfunctional ER chaperone activity can affect glucose metabolism by decreasing glycolysis and mitochondrial respiration. Consistently, our bulk RNA-Seq analysis of reactive astrocytes shows that
Nhe1
Astro-KO astrocytes exhibit significantly stimulated transcriptome profiles for glycolysis (
Hk2, Gpi,
and
Ldhb) and
oxidative phosphorylation (complex I, IV and V). Together, our study demonstrates that restoring astrocytic ER chaperon function and glucose metabolism via specific deletion of
Nhe1
promotes neuron survival after ischemic stroke.
Abstract P731: Genetic Knockout of Cd38 Protects Mice Against Ischemic Brain Injury
Authors: Hannawi Yousef , Ewees Mohamed G , Zweier Jay L
Published: March 2021

Introduction:
CD38 is an ectoenzyme that is present on the cellular membranes of endothelial cells and subtypes of inflammatory cells. We have shown that ischemia/reperfusion (I/R) in the heart triggers CD38 activation that in turns leads to NADPH depletion and endothelial nitric oxide synthase (eNOS) impairment. This cascade results in worsening of ischemic injury secondary to endothelial dysfunction. We hypothesize that a similar paradigm exists in acute ischemic stroke and that loss of CD38 function is protective against cerebral I/R injury.

Methods:
Middle cerebral artery occlusion (MCAO) was performed for 60 minutes in 15 week-old CD38 knockout mice (KO) n=12 and wild type (WT) mice n=12. Stroke volume was calculated using T2 MRI sequences obtained at 48 hours post MCAO. Percentage of brain infarction volume compensated for swelling (IFV) was calculated by manual segmentation of the stroke area and non-affected cerebral hemisphere. Following brain MRI, H&E staining and immunohistochemistry assessment of superoxide radicals (DHE fluorescence) nitric oxide (NO) (DAF fluorescence), eNOS expression, CD38 expression and microglia activation (Iba1) were performed. (P<0.05) was considered significant in statistical testing.

Results:
CD38 KO mice had a smaller IFV as % of the normal contralateral hemisphere volume compared to WT (19.6±3 vs 33.5±9, P=0.001). Both western blotting and immunohistology confirmed lack of CD38 expression in CD38 KO mice. CD38 expression was 55% higher in the ipsilateral stroke side compared to the contralateral stroke side in WT mice (P=0.0105). Compared to WT mice, CD38 KO had 45% lower superoxide levels (P<0.001), 50% higher NO levels (P<0.05) and 46% lower Iba-1 expression with more significance in ipsilateral side (P<0.01) than contralateral side (P<0.05). While eNOS expression was 40% lower in WT vs CD38 KO, this did not reach statistical significance.

Conclusions:
Thus, genetic deletion of CD38 is protective against cerebral ischemia with reduced superoxide production and preserved NO production, likely through the protection conferred against NADPH depletion. These results suggest that inhibition of CD38 could serve as a potent therapeutic approach to protect against acute ischemic stroke and related brain I/R injury.
Abstract P733: Astroglial Activation Following Stroke Contributes to Impaired Synaptic Plasticity Through Increased Cd38-trpm2 Channel Signaling
Authors: Burch Amelia M , Orfila James E , Dietz Robert , Dingman Andra , Mitchell Danae , Wassermann Benjamin , Quillinan Nidia , Herson Paco S
Published: March 2021

Introduction:
Post-stroke cognitive impairment (PSCI) is a major contributor to long-term disability following acute ischemic stroke. Learning and memory deficits are a common feature of PSCI and alterations in hippocampal function are a likely contributor. Interestingly, common experimental stroke models (middle cerebral artery occlusion; MCAO) cause hippocampal dysfunction, despite no direct ischemic insult to the hippocampus, suggesting perturbations in neural circuits. Thus, we utilize electrophysiological recordings of hippocampal plasticity in combination with neurobehavioral assessments of memory function.

Hypothesis:
Activated astrocytes in the hippocampus following MCAO increase expression of the surface enzyme CD38, which signals to neurons to impair plasticity.

Methods:
Extracellular field recordings of CA1 neurons were performed in acute hippocampal slices prepared 30 days after recovery from transient MCAO (60 min) in adult (6-8 week) mice. A behavioral fear conditioning paradigm (CFC) was used to evaluate contextual memory. Immunohistochemistry was performed to assess CD38 expression and slices were treated with CD38 inhibitors (78c) to assess plasticity.

Results:
Recordings obtained in brain slices 30 days after MCAO exhibited loss of hippocampal LTP; 134±6%, n=4 in sham and 107±12%, n=4 30 days after MCAO. Memory function, measured using CFC, was consistent with our LTP findings. MCAO decreased freezing behavior, indicating lack of memory (65±7% in sham mice (n=6) and 37±7% in MCAO mice, n=7). Immunohistochemical data indicates increased CD38 expression in activated astrocytes following MCAO in the hippocampus. Treatment of hippocampal slices with 78c, a potent CD38 inhibitor, after MCAO rescues LTP impairment. Finally, no additive increase in LTP when 78c is co-administered with a TRPM2 channel inhibitor was observed.

Conclusion:
These data indicate that MCAO is a reproducible model of post-stroke memory dysfunction (PSCI) and remote astrogliosis in the uninjured hippocampus may contribute to altered neuronal function (plasticity). Our data implicates increased levels of CD38 as an upstream activator of neuronal TRPM2 channel in the hippocampus following stroke, resulting in impaired synaptic plasticity.