bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP150: Autophagy Regulates NLRP3 Inflammasome in Cerebral Ischemia With Comorbid Stress: A Protective Mechanism of Progesterone
Authors: Espinosa-Garcia Claudia , Atif Fahim , Yousuf Seema , Sayeed Iqbal , Neigh Gretchen N , Stein Donald G
Published: January 2019

Introduction:
Exposure to stress primes microglia and the NLRP3 inflammasome, resulting in an exaggerated inflammatory response to a secondary insult such as stroke. NLRP3-mediated inflammation can be regulated by the autophagic removal of inflammasome activators, components, or cytokines. We hypothesized that progesterone (PROG), a neuroprotective neurosteroid, would enhance autophagy in a rodent model of cerebral ischemia combined with stress, and in an
in vitro
inflammasome assay.

Methods:
Adult male rats were exposed to social defeat stress for 8 days and then subjected to global ischemia. PROG (8 mg/Kg) was administered 2 and 6 h after occlusion, then daily for 7 days. At 7 and 14 days post-ischemia, hippocampi were dissected and autophagic flux was evaluated by western blot using LC3-II and p62 as indicators. To activate the NLRP3 inflammasome
in vitro
, cultured primary mouse microglia were primed with 1 ug/mL LPS for 2 h prior to stimulation with 5 mM ATP (a classical inflammasome activator) for 1h, and concomitantly treated with PROG. IL-1b production was measured by ELISA, while LC3 puncta were detected by immunofluorescence.

Results:
After social defeat, no changes in LC3-II levels were observed, but p62 levels slightly decreased. Global ischemia impaired autophagy as evidenced by decreased LC3 and p62 levels compared to non-ischemic controls. Stressed ischemic animals showed lower LC3 and p62 levels than ischemic animals. Notably, PROG enhanced autophagy, LC3 levels were increased and p62 reduced in both stressed and non-stressed ischemic animals. LPS and ATP synergized in compromising microglial autophagy and worsened IL-1b production. LPS-primed microglia treated with PROG showed enhanced autophagy, a larger number of LC3 puncta, and reduced IL-1b production compared to untreated controls. PROG’s beneficial effects were blocked by 3-methyladenine, an autophagy inhibitor. We conclude that PROG reduced the neurotoxic potential of primed microglia via autophagy, and attenuated NLRP3 inflammasome overactivation. These findings provide new insight into the mechanisms underlying PROG’s protective effects on the excessive inflammatory response, particularly important for improving outcome in stroke patients with comorbid stress.
Abstract WP151: Ischemic Injury in Diabetes Augments Cerebral Microvascular Matrix Metalloproteinase Activation in Female Rats
Authors: Abdul Yasir , Jamil Sarah , Dong Guangkuo , Li Weiguo , Fagan Susan , Ergul Adviye
Published: January 2019

Introduction:
Diabetic female patients are at greater risk of stroke and worsened recovery. We have previously shown that matrix metalloprotease 3 (MMP3) exacerbates hemorrhagic transformation (HT) in hyperglycemic stroke in male rats while high glucose and hypoxia increases MMP3 activity in brain microvascular endothelial cells (BMVECs). Furthermore, diabetic female rats develop greater HT. Current study was designed to test the hypothesis that ischemic stroke increases the cerebral microvascular MMP3 activity in diabetic female animals.

Methods:
Female rats after 7-8 weeks of diabetes (high fat diet and low dose of streptozotocin) were subjected to 60 min MCAO. After 3 days, adhesive removal time (ART) and behavioral composite score were measured and cerebral microvessels were isolated. Human female BMVECs were grown under normal (5.5mM glucose) or diabetic condition (25mM glucose plus 100μM sodium palmitate) for 48 hours, followed by hypoxia insult for 12 hours (200μM cobalt chloride). Cell lysate, media and microvascular homogenates were analyzed for MMP profiling by immunoblotting, zymography and MMP3 enzyme activity by fluorescence resonance energy transfer (FRET) assay.

Results:
MMP3 protein expression and activity were significantly increased in the ischemic microvasculature and this was accompanied by a worse neurobehavioral score (Table 1). In vitro, expression of MMP3, 2 and 9 proteins in cell lysate were not different between the groups. However, MMP3 and MMP9 enzyme activities were significantly increased in the diabetes condition while, there was no additional increase in enzyme activity with hypoxia. MMP2 activity was significantly increased with hypoxia in diabetes condition (Table 1).

Conclusions:
In female rats, diabetes and hypoxia increase MMP activity in the microvasculature and endothelial cells. These observations provide initial evidence to further explore the role of MMPs in the increased HT seen in females with diabetes.
Abstract WP157: Beneficial Effects of Collateral Augmentation by Acetazolamide and Head-Down Tilt in Rat Ischemic Stroke Model
Authors: Han Minho , Kwon Il , Ha Jimin , Choi Hyun-Jung , Heo Ji Hoe , Nam Hyo Suk
Published: January 2019

Introduction:
We investigated whether collateral augmentation treatments with acetazolamide (ACZ), head down tilt (HDT), or combination are effective in rats with the transient middle cerebral artery occlusion (MCAO) models.

Methods:
All animals were induced MCAO for 1h 30min and reperfusion for 24h. ACZ 100 mg/kg solution in 0.9% saline was administered in a single intravenous bolus of 0.5 ml over 3 min, 30 min after onset of MCAO. HDT was administered using a 15° tilted platform for 60 min, 30 min after onset of MCAO. To measure infarct volume, brain water content and neurological score, 58 male Wistar rats were divided into four groups: control (n=17), ACZ (n=15), HDT (n=13) and combination groups (n=14). Infarction volumes were measured after 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurologic deficits were assessed using the Garcia and Longa scores at 24h after MCAO. The following formula was used to quantify the brain water content: brain water content (g) = wet brain weight - dry brain weight.

Results:
The collateral augmentation groups had smaller infarct volume (control, 30.39 ± 8.18 vs. collateral augmentation groups 16.89 ± 11.45, p=0.005) and less brain water content (control, 1.53 ± 0.11 vs. collateral augmentation groups 1.44 ± 0.10, p=0.081). Neurological scores were better in collateral augmentation group than control group (Garcia score; control, 9.8 ± 2.1 vs. collateral augmentation groups, 12.4 ± 3.0, p=0.001) (Longa score; control, 2.5 ± 0.8 vs. collateral augmentation groups, 1.9 ± 1.1, p=0.026). Among groups, the ACZ group was significantly associated with small infarct volume (ACZ, 11.79 ± 5.40 vs. control, 30.39 ± 8.18, p<0.001), followed by the combination group. In addition, the combination group was significantly associated with better neurological scores (Garcia score; combination, 13.33 ± 2.46 vs. control, 9.79 ± 2.12, p=0.017) and less brain water content (combination, 1.35 ± 0.09 vs. control, 1.53 ± 0.11, p=0.031).

Conclusion:
We found that collateral augmentation was associated with smaller infarction volume and better neurological outcome compared to untreated animal after transient MCAO. Among the treatment methods, the combination group showed the best beneficial effects.
Abstract WP17: Blood Pressure Reduction Within 24 Hours After Mechanical Thrombectomy Does Not Correlate With Outcome: A Collaborative Pooled Analysis
Authors: Anadani Mohammad , Orabi Yser , Alawieh Ali , Goyal Nitin , Pandhi Abhi , Mitchell Hunter , Alexandrov Andrei , Maier Ilko L , Psychogios Marios-Nikos , Liman Jan , Inamullah Ovais , Swisher Christa , Rahman Shareena , Kansagra Akash , Giles James A , Allen Michelle , Wolfe Stacey Q , Kan Peter , Nascimento Fábio A , Turner Raymond D , Spiotta Alejandro M
Published: January 2019

Introduction:
Previous studies showed that lowering blood pressure in the acute phase after stroke may be harmful. However, the effect of blood pressure lowering on outcome after successful recanalization is not well known.

Objective:
The aim of this study was to evaluate the association between systolic blood pressure (SBP) reduction and outcome of thrombectomy after successful recanalization.

Methods:
This was a retrospective multicenter study of patients with anterior circulation large vessel occlusions who achieved successful recanalization (TICI 2b-3) with MT. Degree of SBP reduction was calculated using the following formula: 100*(admission SBP - minimum SBP within 24 hours)/admission SBP. Patients were divided into two groups: group 1) included patients with ≤25% SBP drop; group 2) included patients with > 25% SBP drop. Outcome measures included 90 days mRS, symptomatic ICH (sICH), and mortality

Results:
Of 991 screened patients, 917 had available admission SBP data. Average age was 68+14 years. The average admission SBP was 143 ±27 mm Hg. 383 (38.6%) patients had less than 25% SBP reduction, whereas 495 (49.9%) had > 25% SBP reduction in the first 24 hrs. There was no difference in the proportion of patients who achieved good outcome (mRS) between the two groups. Likewise there was no difference in the rate of sICH between two groups (4..2% vs. 4.5%;p=0.84). SBP reduction was not significantly associated with functional outcome on multivariate analysis (OR=1.003; 95% CI 0.99-1.013, p=0.54).

Conclusion:
blood pressure lowering after successful recanalization appears to be safe and was not associated with worse outcome. Further studies are needed to determine whether BP lowering is actually beneficial
Abstract WP173: Characteristics and Prognostic Factors for the Imaging Outcomes in Cervicocerebral Artery Dissection
Authors: Lee Jun , Kim Min-Gyeong , Jeong Da-Eun
Published: January 2019

Introduction:
Although cervicocerebral artery dissection is a common cause of ischemic stroke in young adults, the effectiveness of imaging findings in predicting outcomes is not well established. We aimed to identify the baseline characteristics and imaging outcomes as well as prognostic factors which influence imaging outcomes for cervicocerebral artery dissection.

Methods:
We included 190 consecutive patients who presented with ischemic symptoms associated with cervicocerebral artery dissection on baseline vascular images. Imaging findings on the baseline were obtained within 7 days after symptom onset, and follow-up vascular images were performed at 3 months, 6 months, or 1 year. We compared the imaging features and the degrees of recovery (complete or partial recovery) between the baseline and follow-up vascular images.

Results:
A total of 133 patients who underwent vascular imaging at baseline and either 6 months or 1 year were compared for these analyses. The median interval between baseline symptom onset and the first vascular imaging was within 24 hours (IQR 0, 1). Regarding the lesion sites, a dissection was more common in the intracranial arteries (78.2%) than the extracranial (21.8%). The most common site of dissection was the vertebral artery (51.1%) with V4 being the most common (38.3%). Follow-up images showed partial or complete improvement of the dissected vessels in 53% (95% CI, 42-63%) at 6 months and 91% (95% CI, 83-95%) at 1 year. The lesions with stenotic/occlusion revealed better imaging recovery compared with lesions with an aneurysm (67.6% vs. 21.3% at 6 months, p<0.002; 85.7% vs. 27.7% after 1 year, p<0.002). After adjustment for the age, gender, and eGFR, a multivariate analysis proved that dyslipidemia (OR 8; 95% CI, 2.6-24.4; p<0.001) and a lesion site on the vertebral artery (OR 2.6; 95% CI, 1.1-6.1; p=0.026) were independent predictors of poor imaging outcome.

Conclusions:
In patients who were diagnosed with cervicocerebral artery dissection based on baseline vascular images, the rate of complete or partial improvement was over 50% in the 6-month follow-up images. Dyslipidemia and vertebral artery dissection were poor prognostic factors for the recovery of the vascular lesion after cervicocerebral artery dissection.
Abstract WP175: The Significance of Perfusion Computed Tomography in the Prediction of Hyperperfusion After Carotid Endarterectomy
Authors: Morita Takumi , Ishibashi Ryota , Yamamoto Hiroyuki , Hayashi Tomoko , Fujimoto Yuki , Takada Kensuke , Ujihara Masaki , Uesato Minami , Yamashita Hokuto , Kinosada Masanori , Kurosaki Yoshitaka , Handa Akira , Chin Masaki , Yamagata Sen
Published: January 2019

Purpose:
Cerebral hyperperfusion syndrome (CHS) is a rare devastating complication associated with hyperperfusion after carotid endarterectomy. Single photon emission computed tomography (SPECT) is usually used with acetazolamide challenge to measure the cerebrovascular reserve (CVR), and a decreased CVR is indicative of a high risk of post CEA hyperperfusion. However, acetazolamide administration can rarely cause serious adverse effects, and thus, alternative methods may be required. Perfusion computed tomography (PCT) is a rapid, more accessible modality, which can be acquired with CT angiography. PCT seems to be useful as a screening tool in identifying groups at high-risk of hyperperfusion, but its usefulness has not sufficiently investigated. Our purpose was to clarify the relationship between hyperperfusion and the preoperative PCT parameters of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT).

Method:
We included patients who underwent carotid endarterectomy in our hospital from 2014 December to 2018 April. PCT was obtained preoperatively and on postoperative day 1. Hyperperfusion is defined as a postoperative CBF of the middle cerebral artery area which has increased twice that of the preoperative value. CHS was defined as any symptom and imaging findings related with hyperperfusion, which include headache, seizure, neurological dysfunction, and any intracranial hemorrhage in the related area. Preoperative CBF, CBV, MTT and other patient characteristics are statistically analyzed between a hyperperfusion group and non-hyperperfusion group.

Result:
There are 73 patients who underwent CEA during the study period, and hyperperfusion was observed in 5 cases, from which 2 were considered as CHS. In the hyperperfusion group, the preoperative CBF was significantly lower (p=0.0008), and the CBV and MTT significantly higher (p=0.0196, p=0.0002). ROC analysis showed that the PCT parameters with the maximal area under the receiver-operating characteristic curve for hyperperfusion was preoperative MTT with an optimal threshold at 8.0 seconds (sensitivity 100%, specificity 100%).

Conclusion:
Patient with prolonged preoperative MTT tend to develop hyperperfusion, which is related to CHS.
Abstract WP187: Significant Recovery From Acute Visual Deficits to Three to Six Months Post Ischaemic Stroke
Authors: Wijesundera Chamini N , Crewther Sheila , Vingrys Algis , Wijeratne Tissa
Published: January 2019

Introduction:
This study considers changes in vision from acute phase of ischemic stroke to 3-6 months post ischemic stroke.

Methods:
We tested Fifty ischemic stroke patients (age 32-95) within a week (mean:day3) of admission to Sunshine Hospital at the bed side using an iPad tablet, between July to December, 2017.We excluded: existing eye disease (twenty), cannot comprehend test (four) and unreliable testing (five).Testing was performed using the Melbourne Rapid Field (MRF-neural) Application for Visual Acuity, Visual Acuity in Noise and Visual Fields. The Eye-Hand co-ordination (EHC) was evaluated with timing of completing a tracking task generated by the iPad (UNSW L-R Eye Hand Coordination Application). The MRF-neural assays high contrast acuity (Landolt C optotype) and acuity targets immersed in luminance noise. It presents a modified 24-2 pattern (20 deg eccentricity and 4 foveal spots) for visual field testing. The results of the stroke group were compared to 30 age similar normal volunteers (controls). All participants provided written consent.These tests were repeated in cases who had abnormality 3-6 months later to determine long-term change or recovery.

Results:
During the acute phase, most stroke cases have normal high contrast visual acuity (p=0.11) but 46% return reduced acuity-in-noise (p<0.000). 62% cases have visual field defects (MD, p<0.000) with the majority (96%) being hemianopic or quadrantanopic. 34 of stroke cases (68%) return abnormal EHC tracking times (p<0.000). Failing at any of the tests (>95%) identifies 47 (94%) ischemic stroke cases as having abnormal visual capacity. At follow up: improvement was found in 73% cases for acuity in noise, 53% cases with visual field loss and 20% of cases with prolonged EHC. In 2 patients (13%) EHC was normal during the acute phase but showed deterioration over the recovery.

Conclusion:
Acute stroke cases (94%) have some form of vision abnormality on admission to hospital, despite near normal high contrast acuity. After 3-6 months, acuity-in-noise and visual fields normalize in the majority of cases but EHC shows variable outcomes.
Abstract WP19: How Many Patients With Acute Ischemic Stroke Are Eligible to Apply Dawn and Defuse 3 Mismatch Criteria? Results From a Prospective Stroke Center Datebase
Authors: Prakapenia Alexandra , Barlinn Kristian , Barlinn Jessica , Pallesen Lars-Peder , Siepmann Timo , Haedrich Kevin , Abramyuk Andrij , Gerber Johannes , Linn Jennifer , Puetz Volker
Published: January 2019

Background:
Recent clinical trials have proven efficacy of endovascular therapy (EVT) for anterior circulation large vessel occlusion (acLVO). The DAWN and DEFUSE 3 trials have selected patients for EVT beyond 6h from symptom onset. We sought to determine how many patients of our center would qualify to apply advanced DAWN or DEFUSE 3 imaging criteria based on clinical symptoms and imaging with non-contrast CT (NCCT) and CT angiography (CTA).

Methods:
We prospectively registered consecutive ischemic stroke patients who were screened for EVT eligibility between 01/2016 and 12/2017. Of these patients, we identified those who fulfilled DAWN (age ≥18years, pre-morbid mRS score ≤1 , NIHSS score ≥10, onset-to-CT time 6-24 hours) and DEFUSE 3 (age 18- 90 years, pre-morbid mRS score ≤2, NIHSS score ≥6, onset-to-CT time 6-16 hours) inclusion criteria, respectively. Of these, we identified patients with acLVO on CTA and early ischemic changes in ≤1/3 of the middle cerebral artery territory (DAWN) or NCCT-ASPECTS >6 (DEFUSE-3), respectively.

Results:
Among 1011 patients who presented during the study period, 362 patients (36%) had an onset-to-CT time between 6-24 hours and 244 patients (24%) between 6-16 hours. Among the 6-24 hours cohort, 62 patients had an NIHSS score ≥10. Of these, 30 patients had acLVO of whom 13 patients had early ischemic changes ≤1/3 of the MCA territory on NCCT. Among the 6-16 hours cohort, 69 patients had an NIHSS score ≥6. Of these, 33 patients had acLVO of whom 18 patients had a NCCT-ASPECTS >6. Despite early ischemic changes in ≤1/3 of the MCA territory in 320 patients presenting >6 hours from symptom onset, no acute vascular imaging was performed in 108 patients. Overall, 19 patients (2% of the complete cohort) fulfilled clinical and imaging criteria utilized in DAWN or DEFUSE-3 trials. Of these, only 10 patients (1% of the complete cohort) received additional perfusion CT of whom 7 patients eventually underwent EVT.

Conclusions:
Only a minority (2%) of patients in our cohort would have qualified to apply advance imaging criteria based on DAWN or DEFUSE-3 trials for EVT beyond 6 hours from stroke onset. However, the positive results of these trials may have an impact on future assessment of EVT eligibility in patients presenting at a later time window.
Abstract WP196: MicroRNA and IGF-1 as Predictive Biomarkers for Stroke Outcomes
Authors: Selvamani Amutha , Lewis Debbie , Lewis Brandon , Spohn MIcheal J , Sohrabji Farida
Published: January 2019

Background:
Although several studies focus on biomarkers for stroke diagnosis, few studies have identified biomarkers that predict stroke recovery. In our preclinical studies, we identified that the peptide hormone insulin-like growth factor (IGF-1) and specific small non-coding RNA (miRNA) are inversely corelated with stroke severity as measured by infarct volume. The objective of this study is to assess the potential of miRNA and IGF-1 to serve as predictors of stroke outcomes in patients as assessed by NIHSS at 90 days after stroke.

Methods:
Male and female patients ages (19-91) years were enrolled at the emergency department of a local hospital. NIHSS scores were obtained at presentation, discharge from the hospital, and 90-day follow-up. Scores were binned into mild (1-4), moderate (5-20) and severe (≥ 21). Prospective blood specimens were collected from the participant within 24 hours of presentation to the emergency department and at 90
+
7 days after initial presentation. Plasma IGF-1 levels were estimated using the Quantikine ELISA for human IGF-1 and and miR-363 expression was determined by qRT-PCR using hsa-miR-363-3p primers. IGF-1 and mir363-3p levels from blood samples collected within 24h of presentation were correlated with binned NIHSS-90 days, separately for males and females.

Results:
In males, there was no correlation between the degree of stroke severity at 90 days with either IGF-1 levels or mir363-3p. In females, there was significant inverse correlation between IGF-1 levels and NIHSS-90d scores (r=-0.467; p<0.05), indicating that higher IGF-1 levels were predictive of better stroke recovery. However, miR-363 levels did not correlate with the 90d NIHSS.

Conclusion:
These pilot data suggest that IGF-1 is a strong predictor of stroke severity in females and has the potential to serve as a surrogate measure for stroke recovery. Supported by TAMUOVPR and TBSI seed grant to FS
Abstract WP220: Developing a Telestroke State Mapping Tool to Improve Stroke Outcomes in Rural Populations
Authors: Hillman Diane G , Divers Marcus C , McMurry Timothy L , Solenski Nina J
Published: January 2019

Background:
Telestroke improves care to geographically isolated populations. The “Stroke Belt”, defined by stroke mortality and hospitalization data, persists across large rural parts of southern U.S.
Using CDC data, we evaluated the impact of 10 variables on stroke outcome within Virginia by county (VA).

We hypothesize that economic factors in addition to poor access to a PSC, result in worse stroke outcomes

.
By introducing
better-targeted low cost telestroke services
, AIS burden could be reduced.

Methods:
Data from the 2015 CDC Stroke & Heart Atlas, and FCC, on broadband access, proximity to PSC, PCP supply, socio-demographics (income/unemployment/rural-population/lack of HS education) and HTN death, were analyzed for the outcome metrics: hospitalizations and mortality. Using 3 analytic approaches we developed a “Community Need Index” by ranking and categorizing each of 10 independent variables to identify counties with the most deleterious series of inputs, then ranked and mapped the results. Using the Kruskal-Wallis test we determined the relationship between the independent and dependent variables to identify predictors of negative outcomes. Using ArcGIS we layered 30min drive times to the nearest PSC over the map of VA stroke M&M.

Results:
SC VA had the greatest burden of stroke disease and lack of resources, exceeding the long recognized Appalachian region as the most disadvantaged region within the VA Stroke Belt.
The strongest predictors of stroke M&M were low income, unemployment, lack of HS education, and deaths from HTN (p=0.00). Broadband availability and PCP ratio, had lower or no correlation (respectively).
Approx. 20% of the VA pop. (1.5mil) reside > 30min from a PSC, with a high proportion in SC Va.

Conclusions:
Poverty, low employment/income, and minimal education are strongly correlated with poorer stroke outcomes.
We present a novel objective state-wide mapping model for stroke M&M which includes critical economic/educational factors to better guide state & federal healthcare & economic investments within the state.
Low cost telestroke services could be provided by all major U.S. state hospitals to ameliorate these gaps, particularly as FCC broadband services are expanding in rural U.S. regions.
Abstract WP226: Predictors of Delayed Hospital Arrival After Onset of Stroke Symptoms in Black and Hispanic Stroke Survivors
Authors: Chan Monica , Ogunlade Adebayo O , Joseph Jennifer , Williams Stephen K , Spruill Tanya , Teresi Jeanne , Williams Olajide , Ogedegbe Gbenga
Published: January 2019

Introduction:
Delayed hospital arrival (DHA) after onset of stroke symptoms often precludes minority stroke victims from life-saving interventions. We sought to identify predictors of DHA in a cohort of Black and Hispanic stroke survivors.

Methods:
We analyzed data from a clinical trial comprising Blacks and Hispanics with recent stroke recruited from New York City stroke centers. Variables associated with pre-hospital behaviors were abstracted from medical records. DHA was defined as arrival to ER >4.5 hours after symptom onset. A GEE model assuming a binomial distribution with a logit link was used in all multivariate analyses adjusting for demographic variables, recurrent stroke, stroke severity, stroke symptomatology, stroke type, being alone at symptom onset, and mode of transportation.

Results:
Data was available for 209 Hispanics and 202 Blacks. The sample was 44% female with average age 61.9±11.0 years. Annual income was reported to be <$15,000 in 50% of participants, while 42.2% reported less than high school education. The index stroke was a recurrent stroke in 35.4% of participants and 75.8% were ischemic. Motor symptoms were the predominant symptom (45.7%). Average baseline stroke severity (NIHSS score) was 4.5±4.8. Majority of participants (64.0%) reported being alone at symptom onset and a minority were transported by EMS (35.5%). The frequency of DHA was 76.4%. Use of EMS was associated with a decreased likelihood of DHA (OR=0.17, 95% CI=0.10-0.31). Being alone at symptom onset was associated with increased likelihood of DHA (OR=2.49, 95% CI=1.36-4.55). DHA was not associated with race/ethnicity, education or recurrent stroke. There was a decreased likelihood of EMS use if: 1) participant was alone at symptom onset (OR=0.19, 95% CI=0.11-0.34), and 2) if stroke symptoms were sensory in nature (OR=0.11, 95% CI=0.03-0.44).

Conclusions:
The frequency of DHA is high and is associated with a failure to activate EMS. The failure to activate EMS may be related to the experience of non-motor symptoms and is associated with being alone during symptom onset. Stroke education efforts should emphasize development of an action plan for alerting EMS that can be implemented when alone and emphasize that stroke symptoms are often non-motor in nature.
Abstract WP235: Hepatocyte Growth Factor and Risk of Stroke in the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Gillett Sarah R , Koh Insu , Zakai Neil , Judd Suzanne , Plante Timothy , Howard George , Cushman Mary
Published: January 2019

Introduction:
Hepatocyte growth factor (HGF) is a cytokine produced in response to tissue injury and endothelial dysfunction and is correlated with cardiovascular risk factors including hypertension and diabetes.

Hypothesis:
HGF is associated with risk of stroke, and racial disparities in stroke may be explained by differences in HGF level.

Methods:
The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled 30,239 black (42%) and white (58%) Americans age 45 and older from 2003-2007. In participants free of baseline stroke, HGF level was measured in a case-cohort study of 534 participants who developed ischemic stroke over 5.4 years and a cohort random sample of 1017 participants. Multivariable linear regression was used to determine correlates of HGF in the cohort random sample. Hazard ratios of stroke by HGF quintile were calculated using Cox proportional hazards models adjusting for stroke risk factors and correlates of HGF.

Results:
HGF was higher with older age, male sex, cardiovascular disease, smoking, warfarin use and higher CRP, but did not differ by race. Main results are in the figure. Those with HGF in the highest vs. lowest quintile had an HR of incident stroke of 2.12 (CI 1.31-3.41) in the model adjusted for Framingham stroke risk factors. There was no difference in the association by sex or race (
p-
interaction > 0.2). As HGF did not differ by race it did not mediate the black-white disparity in stroke incidence.

Conclusion:
In REGARDS, HGF in the top quintile was associated with a doubling of incident ischemic stroke risk after adjusting for other stroke risk factors. HGF did not mediate the black-white disparity in stroke risk.
Abstract WP24: Impact of Blood Pressure Control in First 24 Hrs Post-Thrombectomy
Authors: Elangovan Cheran , Niazi Muhammad , Deturk Nathan , Richardson Alicia , Velasco Cesar , Liu Kenneth , Ermak David
Published: January 2019

Introduction:
The importance of blood pressure control after IV tPA is well known. Current practice is to use these same parameters for patients undergoing Endovascular Thrombectomy (ET). However, optimal blood pressure control following ET is not well defined, the DAWN trial used a target of <140mmHg in their study population and there is retrospective evidence that a target of <160mmHg is associated with good outcomes. Herein, we provide retrospective evidence in regards to likelihood of good outcomes based on relative SBP control after successful ET.

Methods:
A retrospective analysis of patients who underwent ET was conducted from January 2017 to April 2018 yielding 92 patients; those with unsuccessful recanalization or incomplete data were excluded leaving 51 for final analysis. Patients were dichotomized in two groups based on good (mRS ≤ 2) and bad (mRS ≥3) outcomes. We performed an ROC analysis to determine the percentage of time that SBP exceeded 140mmHg in order to be associated with a poor outcome at 90 days.

Results:
ROC analysis found that when 45% of SBP readings exceeded 140mmHg, there was a poor outcome at 90 days with sensitivity and specificity of 61 and 82%, respectively. The AUC of this analysis was 0.71 with a p-value of <0.05. The PPV and NPV for this cutoff were 80% and 66%, respectively.

Conclusion:
The percentage of time that SBP exceeds the target of 140mmHg in the first 24 hours appears to have an independent correlation with outcome in patients after successful ET. Those patients with uncontrolled SBP, defined as SBP >140mmHg 45% of the time or more experienced a poor outcome in 80% of cases. Those patients with controlled SBP, defined as <140mmHg 55% of the time or more experienced a good outcome in 82% of cases. Our study has obvious limitations due to the retrospective nature of the study and small sample size. While the values we studied for SBP control do not represent the continuously variable nature of this parameter, they do represent a general trend and are compatible with the standard of care seen amongst facilities providing ET. A randomized controlled trial to study these findings could have great implications to current practice.
Abstract WP242: Modeling Prevention, Prediction or Explanation of Stroke Risk: Insights From Meta-Analysis of Studies With Models Predicting Stroke or Composite Outcomes
Authors: Saxena Anshul , McGranaghan Peter , Das Sankalp , Rubens Muni , Salami Joseph , Veledar Emir
Published: January 2019

Objective:
Models predicting stroke suffer from several problems: they are not accurate, contain mostly non-modifiable factors, and they explain more than they predict. We performed a meta-analysis of frequently used stroke models. Our goal was to estimate the discriminative ability of the concordance statistic by establishing confidence and predictive intervals.

Methods:
Studies with most representative predictive methods were used in our analysis. Inputs in analysis were study-reported c-index values and corresponding 95% CI. Subgroup analysis, separating survival and logistic regression models, and separating models by outcome (predicting stroke or composite outcome) were executed. Combined effect sizes with the random model, test for heterogeneity, and publication bias were considered. Egger’s test was used to assess for funnel asymmetry.

Results:
Fifteen models were included (patients= 13177; LR=7, Cox= 8; only stroke =9, composite=6) in the analysis. Models predicting composite outcomes performed worse (0.62; 95% CI: 0.59, 0.65) than model predicting only stroke (0.70; 95% CI: 0.64, 0.75); combined mean c-index was 0.66 (95% CI: 0.62, 0.70; 95% predictive interval: 0.55, 0.78). Test of heterogeneity showed high variation between studies (I
2
=74.9%). Egger’s test intercept was 1.59 (95% CI: –0.80, 3.98, P > .17).

Conclusion:
At the moment, there is no good quality predictive or explanatory model available for stroke risk. Current models do not indicate towards risk factors exclusive only to stroke. Because of this, models predicting stroke mostly have non-modifiable risk factors. In addition to this, models orienting toward explanation are borrowing heavily from models developed for predicting composite cardiovascular diseases.
Abstract WP243: Randomized Clinical Trial Evaluating the Safety and Feasibility of Intensive Lowering of Blood Pressure in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis and Assessed using CT Perfusion Imaging
Authors: Sharma Vijay K , Tan Benjamin Q , Ngiam Nicholas J , Ng Bridget S , Low Yingliang , Wong Lily Y , Du Zhengdao , Chen Jintao , Paliwal Prakash R , Teoh Hock-Luen , Chan Bernard P , Butcher Kenneth , Anderson Craig S
Published: January 2019

Introduction:
Uncertainty persists over the optimal management of blood pressure (BP) in the early phase of acute ischemic stroke (AIS). This study aims to determine the safety and effects of intensive BP lowering on cerebral blood flow and functional outcomes in AIS patients treated with intravenous thrombolysis.

Methods:
In a randomized controlled trial, AIS patients with a systolic BP of 160-180mmHg were randomized to early intensive BP lowering (systolic target range 140-160mmHg) or guideline-based BP management (systolic range 160-180mmHg) during first 72-hours using primarily intravenous labetalol. All study subjects underwent CT perfusion at baseline, 24 and 72-hours post-randomization to evaluate change in cerebral hemodynamics. Clinical outcome was assessed using a dichotomized modified Rankin scale (scores 0-1 as excellent outcome versus scores 2-6 as poor outcome) at 90 days.

Results:
Of the 48 recruited patients, 25 (52%) were assigned to the early intensive BP lowering arm and 23 (48%) to the guideline-based BP management arm. Excellent functional outcome at 90 days were similar in the 2 arms- 56% in the early intensive BP lowering arm and 61% in the standard therapy arm. There were no significant differences in the baseline, 24 and 72-hour CT perfusion cerebral hemodynamic parameters or symptomatic intracranial hemorrhage between the 2 study arms.

Conclusions:
In the early phase of AIS, intensive BP lowering appears to be a safe strategy. Large randomized controlled trials are needed to confirm our study findings.
Abstract WP245: Demographics, Risk Factors and Outcomes of Stroke in Young Adults Aged 18-45 Years in Comparison With Those Older Than 45 Years
Authors: Nagaraja Nandakumar , Jugl Sebastian , Brown Joshua D , Simpkins Alexis N , Wilson Christina A , Yuzefovich Khanna Anna , Youn Teddy S , Kelly Adam G
Published: January 2019

Introduction:
The prevalence of stroke in young adults have increased with the prevalence of cerebrovascular risk factors in this population. The objective of this study was to compare stroke prevalence in age groups 18-45 years versus more than 45 years by demographics, risk factors, and outcome.

Methods:
We analyzed the National Inpatient Sample Database from the Healthcare Cost and Utilization Project for the years 2008-14. Patients with stroke were identified based on discharge DRG codes 61-66 for acute ischemic stroke with use of thrombolytic therapy, intracranial hemorrhage or cerebral infarction. Demographics, risk factors from comorbid condition codes, and outcomes were analyzed.

Results:
Out of a total of 3,624,243 adult patients with stroke hospitalized during the years 2008-14, 189103 (5.21%) hospitalizations were of patients aged 18-45 years. The ratio of stroke hospitalizations to overall hospitalizations increased from 154 to 185 per 10,000 hospitalizations from the year 2008 to 2014 with increase in stroke hospitalizations in both age groups. Stroke in young adults aged 18-45 years was more common in men, Blacks and Hispanics compared to those older than 45 years. Cerebrovascular risk factors were common in young adults with stroke and the prevalence of obesity, arterial malformation, tobacco use or alcohol abuse was higher in stroke patients aged 18-45 years compared to those older than 45 years (Table 1). There was up to 6% increase in the prevalence of cerebrovascular risk factors from 2008 to 2014. Young adults with stroke aged 18-45 years were more likely to be discharged home while older adults were more likely to be discharged to skilled nursing facility.

Conclusions:
There are gender and racial differences in stroke among adults aged 18-45 years compared to those older than 45 years age. Modifiable cerebrovascular risk factors are common in young adults with stroke. Most notably, both obesity and smoking were particularly higher in younger patients.
Abstract WP250: Trends in Outcomes Associated With Thrombectomy Treatment Among Acute Ischemic Stroke Patients: Retrospective Analysis of 2011-2017 Premier Hospital Database
Authors: Khanna Rahul , Rai Ansaar , Crivera Concetta , Kalsekar Iftekhar , Kumari Rashmi , Patino Nataly , Chekani Farid
Published: January 2019

Objectives:
Mechanical thrombectomy has become the cornerstone of acute ischemic stroke (AIS) treatment. This study evaluated trends in discharge status, length of stay (LoS), operating room (OR) time, readmissions and costs among AIS patients who underwent mechanical thrombectomy treatment.

Methods:
This retrospective cohort study used 2011-2017Q3 Premier Healthcare Database to evaluate discharge status, length of stay (LoS), operating room (OR) time, readmissions, index inpatient costs for AIS patients aged ≥18 years who underwent mechanical thrombectomy. Patients with a diagnosis of AIS in 12-month baseline or with LoS ≤ 1 day were excluded. The Mann-Kendall statistic was used to examine trends in economic and clinical outcomes associated with thrombectomy between 2011 and 2017.

Results:
Among 505,824 patients identified with a primary diagnosis of AIS between 2011 and 2017, 11,811 (2.34%) patients were treated with mechanical thrombectomy. The percentage of AIS patients who underwent thrombectomy significantly increased from 1.33% in 2011 to 4.44% in 2017 (p<0.01). The mean age of patients was 66.47 ± 14.75 years, with 51.97% being male. Among AIS patients who underwent thrombectomy, the discharge to home significantly increased from 17.69% in 2011 to 29.64% in 2017 (p< 0.01), while discharge to long-term facility decreased from 53.47% to 49.69% (p=0.10). Mortality rate significantly decreased from 21.60% to 12.64% during the same time period (p< 0.01). The mean OR time declined from 200.73 minutes (2011) to 170.11 minutes (2017) while LoS significantly decreased by 2.95 days (p< 0.01). All-cause 365-day readmission rate decreased from 24.15% in 2011 to 19.78% in 2017 (P=0.35). The index inpatient hospital cost of AIS patients who received thrombectomy significantly declined from $50,516.54 to $42,026.90 (p< 0.01).

Conclusions:
The economic and clinical outcomes among AIS patients receiving mechanical thrombectomy treatment improved during the study period. However, the overall burden of stroke among patients who received thrombectomy remains high.
Abstract WP251: A Mendelian Randomization Study of Alcohol Intake and Ischemic Stroke in a Han Chinese Population
Authors: Zhang Yonghong , Shi Mengyao , Li Changwei , Wang Aili , Xu Tan , Sun Xiao , Bu Xiaoqing , Chen Jing , Kelly Tanika , He Jiang
Published: January 2019

Introduction:
Observational studies have reported inconsistent relationships between alcohol intake and ischemic stroke risk. The
ALDH2
gene encodes an enzyme critical for alcohol metabolism and can serve as an unconfounded proxy for alcohol intake. The current study examined the association between the
ALDH2
gene and ischemic stroke among 11,753 Chinese participants.

Methods:
The discovery stage included 999 ischemic stroke cases and 1,001 controls with no history of atherosclerotic disease. The
ALDH2
gene was sequenced using the SOLiD 4hq platform. Variants with minor allele count (MAC) >10 were each tested for association with stroke using logistic regression models. Interactions between alcohol intake and
ALDH2
variants were also tested. Aggregate analysis of rare variants (MAC <20) used the sequence kernel association test. Variants with P<1х10
-4
were replicated among 4,724 ischemic stroke cases and 5,029 controls from the China Stroke Project.

Results:
An interaction of alcohol drinking with the
ALDH2
rs671 variant, which encodes an inactive aldehyde dehydrogenase isozyme that limits tolerability to alcohol, on ischemic stroke risk was identified using the 2 degree of freedom test (P=2.77х10
-5
, 3.66х10
-11
, and 1.01х10
-15
in discovery, replication and joint analyses, respectively). Among drinkers, each copy of the variant allele conferred decreased odds of ischemic stroke, with odds ratios (95% CI) of 0.38 (0.25, 0.60), 0.79 (0.69, 0.91), and 0.74 (0.65, 0.85) in discovery, replication and joint analyses, respectively. While no association between the variant allele and stroke was observed among non-drinkers in the discovery stage [odds ratio (95% CI): 1.00 (0.82, 1.23)], the protective relation persisted among non-drinkers in the replication and joint analyses [odds ratios (95% confidence interval): 0.77 (0.71, 0.84) and 0.80 (0.74, 0.87), respectively]. This inconsistency may have resulted from disparate frequencies of former drinkers included in the non-drinking groups. No additional variants were identified.

Conclusions:
This large scale genomic study implicates increased alcohol intake as an etiologically relevant risk factor for ischemic stroke.
Abstract WP276: Predictors of Cardio-embolic Stroke in Therapeutically Anticoagulated Patients With Atrial Fibrillation
Authors: Al-Salaimeh Ayman , Bradley Bruce , Gupta Vedant A , Taylor Deborah , Dobbs Michael , Goldstein Larry B
Published: January 2019

Background:
Anticoagulation reduces the risk of stroke in patients with Atrial Fibrillation(AF) . Ischemic stroke occurs in setting of AF despite adequate treatment because of both cardiac and non-cardiac causes. We hypothesized that certain cardiac abnormalities would increase the likelihood of cardio -embolic stroke(CES) in therapeutically anticoagulated patients with AF.

Methods:
We reviewed the records of all adults who were adequately anticoagulated with warfarin and admitted to our hospital with a diagnosis of ischemic stroke or transient ischemic attack between 01/01/2011 -06/30/2016. Stroke mechanism (CES vs non CES) using ASCOD criteria was determined by a vascular neurologist masked to the echocardiographic results. Cardiac studies were assessed independently by a cardiologist masked to the stroke mechanism. Categorical variables were analyzed with Chi square or Fisher exact test as appropriate. Continuous variables were analyzed using t test. P value <.05 was considered significant. Stepwise logistic regression was used to identify variable independently associated with CES.

Results:
61 patients (39 patients with CES and 22 with non- CES ) were identified. In univariable analyses, CHF (59% vs 22.7%, p=0.006) was more common and Left atrial(LA) dimension (45 vs 39 mm, p=0.0139), LA volume (84 vs 66 mL, p=0.0133), Left ventricular(LV) mass (223 vs 166 gm, p=0.0008) and LV mass index (113.1 vs 92.88 gm/m2, p=0.016) larger with CES vs non- CES. Total cholesterol was higher in non- CES (175.9 vs 132.58 mg/dL, p=.0002). Stepwise logistic regression showed Left ventricular mass, Left ventricular mass index and total cholesterol were independently associated with CES (p=0.005, 0.018, 0.02. respectively).

Conclusion:
Patients with CES despite therapeutic anticoagulation had higher LV mass, LV mass index and lower total cholesterol compared to those with non- CES. Larger prospective studies are required to confirm these findings.
Abstract WP278: Markers of Coagulation and Hemostatic Activation in Embolic Stroke of Undetermined Source (ESUS) Patients With Patent Foramen Ovale
Authors: Sharashidze Vera , Rangaraju Srikant , Rathakrishnan Priyadharshi , Duncan Alexander , Hoskins Michael , Marmarchi Fahad , Belagaje Samir , Bianchi Nicolas , Belair Trina , Henriquez Laura , Monah Kaslyn , Nahab Fadi
Published: January 2019

Introduction:
Recent randomized trials have shown that patent foramen ovale (PFO) closure combined with antiplatelet therapy in cryptogenic stroke patients ≤ 60 years of age is associated with a reduced risk of stroke compared to antiplatelet therapy alone, presumably by preventing a paradoxical embolism. The objective of this study was to evaluate the MOCHA profile, a sensitive marker of venous thromboembolism (VTE), in ESUS patients with PFO.

Methods:
Consecutive ESUS patients ≥ 18 years of age seen in the Emory Clinic from January 1, 2017 to June 30, 2018 underwent testing of MOCHA including serum d-dimer (DD), prothrombin fragment 1.2 (PTF1.2), thrombin-antithrombin (TAT) complex and fibrin monomer (FM). All patients were on antiplatelet therapy at the time of MOCHA testing and an abnormal MOCHA profile was defined as ≥ 2 elevated markers. We compared baseline characteristics and clinical outcomes between patients with and without PFO.

Results:
During the study period, 113 ESUS patients (mean age 64 +/- 15 years, 63% female, 54% non-white, 20% PFO) underwent MOCHA profile testing; 37 (32.7%) were ≤ 60 years of age. In the subgroup ≤ 60 years of age, the 11 (23%) PFO+ patients were younger (mean age 40 vs 46, p=0.009), more likely to be white (55% vs 35%, p=0.0001) and had higher ROPE score (median 8 vs 6, p=0.06) than PFO- patients. There was no significant difference between PFO+ and PFO- patients in the frequency of abnormal MOCHA (18% vs 19%), mean DD, PTF1.2, TAT, FM and frequency of VTE (1 event in each group). PFO+ and PFO- patients had a high frequency of migraine with aura (64%, 38%, p=0.15) and headache days in the month prior to stroke (mean 11 vs 5, p=0.72). In multivariable analysis of the overall cohort, age (OR 1.14 1.06-1.22 p<0.001) and ROPE score (OR 2.29 1.13-4.65 p=0.02) were significantly associated with abnormal MOCHA while PFO status (p=0.4) and migraine (p=0.23) were not.

Conclusion:
In ESUS patients ≤ 60 years of age, there was no difference in the MOCHA profile between PFO+ and PFO- patients. The high frequency of migraine with aura and headache days in the month prior to stroke regardless of PFO status needs further study to evaluate its role in young ESUS patients.