bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP9: Does Repeat Images Improve Patient Selection and Clinical Outcomes in Patients Transferred for Endovascular Thrombectomy?
Authors: Sarraj Amrou , Chen Michael , Goyal Nitin , Hassan Ameer , Kamal Haris , Chen Peng R , Sitton Clark , Cai Chunyan , Cutter Gary , Pujara Deep , Imam Bita , Reddy Sujan , Requena Manuel , Elijovich Lucas , Arthur Adam , Pandhi Abhi , Grotta James , McCullough Louise , Savitz Sean , Abraham Michael , Ribo Marc
Published: January 2019

Background:
It is unknown if repeat imaging of transfer patients for endovascular thrombectomy (EVT) results in better patient selection and improved clinical outcomes or if bypassing repeat imaging and direct transfer to the angiosuite is safe, saves time and improve outcomes.

Methods:
A multicenter retrospective cohort was pooled from 6 centers (Europe and US) from 1/2014 to 4/2018 of patients with anterior circulation occlusion (ICA, M1, M2) transferred for EVT up to 24 hours from last known well. Patients were divided based on imaging acquisition at the EVT center into those who underwent any repeat imaging (CT+/- CTA, CTP) and those who bypassed imaging and went directly to the angiosuite. We compared good outcome (90 day mRS 0-2) and safety (sICH, mortality) between the two groups.

Results:
Of 646 patients, 559 received EVT and 87 were excluded for poor imaging profiles. In patients who received EVT, 173 (31%) had no repeat nd 386 (69%) had repeat images. The two groups had similar age and NIHSS. ASPECTS was lower in the repeat images group 8(7-10) when compared to ASPECTS from the outside facility in the non-repeat 9(8-10), p<0.001. Repeat imaging prolonged arrival to puncture times 65(41-98) in the repeat vs 23(14-62) min for non-repeat group, P<0.001 without correlating with better rates of good outcome (42% repeat vs 51% no repeat (Fig 1), aOR 0.75 (0.39-1.47), p=0.41) and similar safety: sICH (9% vs 6%, p=0.29) and mortality (20% vs 16%, p=0.35). The results did not vary when stratified by early (0-6 hrs) vs late (6-24 hrs) treatment. Matching patients who did not receive EVT due to low ASPECTS with those who underwent EVT with low ASPECTS showed no increase in sICH (0% vs 4%, p=1.0) and better rates of mRS 0-2 with EVT (33%) vs medical management only (7%), p=0.15.

Conclusion:
In patients transferred for EVT, repeat imaging resulted in treatment delays without improving good outcome. Direct angio suite access may result in more patients treated safely who achieve good outcome.
Abstract WMP92: Stroke Quality of Care Measures in Relation to Long-term Mortality in the Florida Puerto Rico Collaboration to Reduce Stroke Disparities (FL-PR CReSD) Study
Authors: Gardener Hannah , Rundek Tatjana , Lichtman Judith H , Leifheit Erica C , Wang Kefeng , Romano Jose G , Sacco Ralph L
Published: January 2019

Introduction:
In the FL-PR CReSD Study, there were race/ethnic disparities in the receipt of defect-free care. How race/ethnic disparities in acute stroke care contribute to disparities in outcomes after stroke is not well understood. We examined the relationship between acute stroke quality of care measures and mortality within the first year by race/ethnicity.

Methods:
The study included fee-for-service Medicare beneficiaries age ≥65 discharged with a primary diagnosis of ischemic stroke in 2010-2013 who were propensity matched with data from 66 CReSD hospitals in FL. Defect-free care included IV tPA treatment, in-hospital antithrombotic therapy, DVT prophylaxis, discharge antithrombotic therapy, appropriate anticoagulation therapy, statin use, and smoking cessation counseling. We used mixed logistic models to assess the associations between stroke care and outcomes (in-hospital, 30 day, 6 month, and 1 year mortality) by race/ethnicity, adjusted for demographics and stroke severity.

Results:
Among 14,100 stroke patients (73% white, 12% black, 15% Hispanic), mortality was 3% in-hospital, 12% at 30d, 21% at 6m, and 26% at 1y. Compared to whites, Hispanics had a greater odds of mortality at all time points, even after adjustment for defect-free care and individual stroke care metrics. Defect-free care was only associated with a lower risk of death within the first year among blacks (OR=0.67, p=0.004). Early antithrombotic use and antithrombotic use at discharge were associated with a lower risk of mortality at all time points, and the protective association for early antithrombotic use was strongest among whites. Statin therapy at discharge was associated with decreased 6m and 1y mortality, but this association was specific to whites and blacks.

Conclusions:
Acute stroke process of care measures, particularly antithrombotic use and statin therapy, were associated with a reduced odds of long-term mortality, particularly among non-Hispanics. Hispanic stroke survivors were at an increased risk of death within the first year, independent of acute stroke care measures. Results underscore the importance of optimizing acute stroke care.
Abstract WMP94: Identifying Opportunities to Improve Hypertension Management Among Hospitals Participating in Michigan’s Ongoing Stroke Registry to Accelerate Improvement of Care (MOSAIC)
Authors: Gray Kimberly A , Nickles Adrienne V , O'Brien Suzanne , Ibrahim Ghada , Wall Samantha R , Quartermus Krystal , Wahl Robert , Scorcia-Wilson Teri , Demel Stacie L , Reeves Mathew J
Published: January 2019

Background:
Hypertension is a leading risk factor for stroke, and its management is key for stroke prevention. Michigan’s Coverdell Acute Stroke Registry collects stroke data including patient history of hypertension and discharge medications. Our aim was to identify independent predictors of having antihypertensive medication prescribed at discharge (AMPD) and to assess hospital-level performance in order to focus future quality improvement efforts.

Methods:
Thirty-one hospitals contributed data to MOSAIC in 2016-2017. Patients with a diagnosis of acute stroke or TIA were included; subjects receiving comfort measures only (CMO), died prior to discharge, or were discharged to hospice were excluded. Patients were considered eligible for AMPD if they had a history of hypertension. Independent factors associated with no AMPD were identified using multivariable logistic regression. Variation among participating hospitals in the treatment of hypertension at discharge was assessed by calculating the percent of hypertension patients with no AMPD.

Results:
Out of 19,645 patients with stroke or TIA, 15,253 (77.6%) had a history of hypertension; 12,707 (83.3%) of these cases did not receive CMO, hospice, were not discharged to an acute care facility and were discharged alive. Of these eligible cases, 934 (7.3%) had no AMPD. No AMPD was significantly higher among subjects who were younger, had hemorrhagic stroke or TIA. No AMPD was significantly lower among blacks (Table). Rates of no AMPD varied widely among hospitals; five hospitals had rates below an achievable benchmark of 15% no AMPD (Range: 2.5 - 70.0%).

Conclusions:
Prescription of antihypertensive medication to patients with a history of hypertension at discharge is high but use occurs less often in younger patients, and those with hemorrhagic stroke or TIA. Hospital-based data identifies substantial variability and identified individual hospitals for follow-up education and quality improvement efforts.
Abstract WP1: Threshold Volume Associated With Higher Survival After Endovascular Recanalization Therapy of Acute Ischemic Stroke
Authors: Shim Dong-Hyun , Kim Youngsoo , Roh Jieun , Kang Jongsoo , Park Kyung-Pil , Cha Jae-Kwan , Baik Seung Kug , Kim Yoon
Published: January 2019

Background and Purpose:
Endovascular recanalization therapy (ERT) is becoming increasingly important in the management of acute ischemic stroke (AIS), but the hospital threshold volume for optimal ERT remains unknown. We investigated whether there was a correlation between hospital volume of ERT and risk-adjusted patient outcomes.

Materials and Methods:
From the National Health Insurance (NHI) claims data, we selected 11,745 AIS patients who underwent ERT from 2011 to 2015, in 111 hospitals. The outcome measures of the study were 30-day mortality, readmission rate, and symptomatic intracranial hemorrhage (ICH) rate. For each outcome measure, risk-adjusted mortality prediction models incorporating demographic variables, modified Charlson comorbidity index, and clinical stroke severity index (SSI) were built, and validated through a comparison with two independent hospital registry-based models. Hospitals were divided into quartiles and risk-adjusted outcomes of AIS cases were compared across the hospital quartile to confirm volume-outcome relationship (VOR) in ERT. Spline regression was performed to determine the volume threshold.

Results:
The mean AIS volume was 14.8 cases per hospital per year and the unadjusted means of outcome variables were mortality 11.6%, readmission 4.6%, and ICH rate 8.6%. The VOR was observed in the risk-adjusted 30-day mortality rate across all quartile groups, and in the ICH rate between the first and fourth quartiles (
p
< 0.05). Volume threshold was 24 cases per year, which was estimated by examining the relative effect on the adjusted odds of outcome for an increase in hospital volume by 10 cases/year for a hospital of a given size.

Conclusions:
We found an association between hospital volume and outcomes, and we identified the volume threshold in ERT. Policies to ensure the implementation of the AIS volume threshold for hospitals performing ERT is needed.
Abstract WP104: Clinical Characteristics of Stroke Mimics Treated on an Urban Mobile Stroke Unit
Authors: Lerario Michael P , Kummer Benjamin R , Wu Xian , Diáz Iván , Pishanidar Sammy , Willey Joshua Z , Mir Saad , Cheng Natalie , Rostanski Sarah K , Efraim Elizabeth S , Crupi Robert S , Schenker Josef , Asaeda Glenn , Bokser Jeffrey , Kamel Hooman , Marshall Randolph S , Navi Babak B , Fink Matthew E
Published: January 2019

Introduction:
It is unknown how the clinical characteristics of stroke mimics treated on Mobile Stroke Units (MSUs) compare to confirmed acute strokes treated on these units.

Methods:
We retrospectively analyzed all patients transported by the NewYork-Presbyterian MSU in New York City from October 2016-May 2018. A vascular neurologist assigned a final diagnosis after comprehensive medical record review. Clinical data were abstracted, including comorbidities, presenting symptoms, stroke severity, acute treatments, and short-term outcomes. We compared characteristics of patients with a stroke mimic diagnosis versus those with acute ischemic or hemorrhagic stroke using targeted minimum loss-based estimation to adjust for demographics, comorbidities, NIH Stroke Scale (NIHSS) score, and intravenous tPA administration.

Results:
Among 92 suspected stroke patients transported by MSU, 56 (61%) had confirmed acute stroke (77% ischemic, 23% hemorrhagic) and 36 (39%) had a stroke mimic. Mimics consisted of seizure (n=8), metabolic encephalopathy (n=6), somatoform disorders (n=4), and others (n=18). The mean NIHSS score was 8 (SD 7) among mimics versus 11 (SD 8) among confirmed strokes (p=0.14). The top presenting symptoms among mimics were unilateral weakness (n=8), aphasia (n=6), confusion (n=6), and decreased consciousness (n=6). Nine mimics (25%) received tPA and none had hemorrhagic conversion; while 30 (53%) confirmed strokes received tPA and 2 (7%) had hemorrhagic conversion. There was no difference in MSU arrival-to-tPA time between groups (46 vs. 44 minutes, p=0.70). In multivariable analyses, compared to patients with confirmed stroke, mimics had significantly lower NIHSS scores, higher initial blood pressures, and shorter lengths-of-stay. Rates of death and discharge disposition were similar between groups.

Conclusions:
Among patients transported by a MSU for suspected stroke, two-fifths were stroke mimics. Seizure, metabolic encephalopathy, and somatoform disorders were the most common mimic diagnoses. Patients with stroke mimics had lower NIHSS scores and less often were treated with tPA.
Abstract WP114: Incidence and Treatment of Unruptured Brain Aneurysms versus SAH in the United States: Trends and Complications over Two Decades
Authors: Golnari Pedram , Nazari Pouya , Ansari Sameer A. , Hurley Michael C. , Shaibani Ali , Potts Matthew B. , Jahromi Babak S.
Published: January 2019

Introduction:
Following publication of ISAT in 2002 showing better outcomes with coiling versus clipping of ruptured aneurysms, there was a substantial increase in endovascular management of ruptured aneurysms. This in turn led to coiling becoming the predominant treatment in both SAH and unruptured aneurysms (UA), as well as an overall increase in volume of aneurysms treated in the USA. However, ISAT did not address UA, and it is unclear if real-world practice trends over the past decade justify this change in both practice pattern and volume.

Methods:
National Inpatient Sample datasets from 1993 to 2015 were obtained and data extracted using ICD-9-CM codes for the diagnosis of UA and SAH, and procedural treatments including clipping and coiling. Age-standardized incidence rates of UA and SAH were estimated. Differences in demographics, hospital characteristics and procedure complications by diagnostic groups were examined, and risk ratios were obtained for factors associated with routine discharge and hospital mortality using poisson regression.

Results:
From 1993 to 2015, overall treatment of UA significantly increased, yet the incidence of SAH did not change (figure 1). A trend towards increasing procedural complications was noted in SAH, likely related to a concomitant trend observed in increasing patient age and comorbidities. In contrast, recent complication rates of UA repair appeared to plateau or slightly diminish (2011-2015). Clipping of UA remained associated with significantly higher risk ratios for complications when compared with coiling and led to fewer favorable discharges.

Conclusion:
We conclude that the age-adjusted incidence of SAH in the United States has remained unchanged throughout the past two decades despite a 3-fold increase in treatment of UA. Modern complication rates of clipping and coiling UA appear relatively stable, with clipping demonstrating significantly higher complication rates and less favorable discharges.
Abstract WP116: Long-Term Results and Predictors of Outcomes in 585 Consecutive Patients Treated With the Pipeline Embolization Device
Authors: Chalouhi Nohra , Mouchtouris Nikolaos , Atallah Elias , Al-Saiegh Fadi , Tjoumakaris Stavropoula , Rosenwasser Robert , Jabbour Pascal
Published: January 2019

Background:
The pipeline embolization device (PED) is the most widely utilized flow diverter. Although the PED was initially designed to treat large and complex aneurysms of the internal carotid artery, its use has now extended to several other indications. Data on the safety and long-term outcomes remain, however, limited.

Objective:
To assess the long-term safety and efficacy of the PED in the largest reported single-center series to date.

Methods:
This is an analysis of a prospectively maintained database at a single-institution. Patients included in the analysis were consecutively treated at Jefferson Hospital for Neuroscience between 2011 and 2017. P2Y12 assays were used. Complications reported both in the perioperative period and through follow-up. Aneurysm occlusion was classified as complete (100%), near-complete (95-99%), or incomplete (<95%).

Results:
A total of 585 patients were included in the study. Mean aneurysm size was 8.5±6.3mm. Aneurysm morphology was saccular in 87.5% and fusiform/dissecting in 11.1%. The mean number of PEDs deployed per aneurysm was 1.2±0.5, decreasing significantly from 1.4±0.7 in 2011-2012 to 1.1±0.3 in 2016-2017 (p<0.001). Additional coiling was performed in 6.5% of patients. Hemorrhage occurred in 3.2% of patients, thromboembolism in 1.2%, device migration in 1.2%, in-pipeline stenosis in 7.3%, and neurological mortality in 1.7%. At a mean angiographic/imaging follow-up of 24.8±19.4 months, complete or near-complete occlusion was seen in 88.5%. Significant predictors of incomplete aneurysm occlusion were older age (OR 1.04, p<0.001), prior treatment of aneurysm (p=0.014, OR 1.93), fusiform shape (OR 2.3, p=0.032) and increasing aneurysm size (OR 1.039, p=0.023). Adjunctive coiling or use of multiple stents was not associated with improved occlusion or decreased complication rates.

Conclusions:
At a high-volume center with experienced operators, treatment with the PED was associated with durable aneurysm occlusion and a low risk of complication. The results support the extension of the indications of flow diversion. Several predictors of outcomes were identified and these should be discussed with patients when considering flow diversion.
Abstract WP120: Readmission Trends Related to Unruptured Intracranial Aneurysm Treatment
Authors: Mehta Tapan , Patel Smit , Male Shailesh , Zhang Andrew , Khan Adam , Narwal Priya , Grande Andrew , Tummala Ramachandra , Jagadeesan Bharathi
Published: January 2019

Introduction:
The treatment of choice for Unruptured intracranial aneurysms (UICA) is dependent on assessment of several factors including aneurysm size, location, and morphology, along with patient's life expectancy and comorbid conditions. Although multiple studies have deliberated upon the efficacy of surgical and endovascular aneurysm treatment for UICA, the rate of readmission with either technique has not been specifically studied.

Methods:
We used the Nationwide Readmission database to assess the readmission trends related to various treatment approaches for UICA. The treatment approaches were subdivided into four groups; surgical clipping group and three endovascular approach groups (coil embolization, stent assisted coil embolization and only stent placement groups). All four groups were compared for the characteristics of index hospitalizations and top causes of readmissions.

Results:
We identified 3533 patients treated with clipping and 4134 (3865 coil embolization, 192 only stent placement and 76 stent assisted coil embolization) patients treated with endovascular approach. Thirty day readmission rate (30RR) was significantly higher with surgical clipping compared to the three endovascular approach groups (8.37% Vs 4.77%, p<0.01). Lower rates of home discharge disposition were observed during index hospitalization (73.8% Vs. 91.4%, p<0.01) and during readmission (53.3% Vs. 72.56%, p<0.01) amongst the clipping group compared to the endovascular groups. Major causes of readmission amongst clipping groups included intracranial hemorrhage (12.9%) and post operative infections (10.5%), Major causes of readmission amongst endovascular group included ischemic cerebrovascular event (21.3%) and headaches (8.6%).

Conclusion:
Patients undergoing endovascular treatment for UICA are less likely to be readmitted and more likely to be discharged home compared to surgical clipping. Given the complex decision making with consideration of anatomic and patient factors for UICA treatment, these findings do not necessarily prove the general superiority of the endovascular approach but do suggest that when a UICA can be safely treated with either technique, the endovascular approach might reduce the chances of readmission.
Abstract WP122: Risk of Intracranial Hemorrhage and National Trends of Delivery Methods of Pregnant Women With Diagnosis of Unruptured Intracranial Aneurysm
Authors: Mehta Tapan , Desai Devashis , Khandwala Pushti , Patel Smit , Male Shailesh , Khan Adam , McCullough Louise , Grande Andrew , Jagadeesan Bharathi , Tummala Ramachandra
Published: January 2019

Introduction:
Understanding the risk of aneurysmal subarachnoid hemorrhage in pregnant women with known history of Unruptured Intracranial Aneurysm (UICA) could potentially impact the delivery method. Due to presumed risk of intrapartum aneurysm rupture, understanding practice patterns of delivery methods and related complication risk is of importance.

Methods:
We used Nationwide Inpatient Sample database (1998-2014) to identify all the hospitalizations for childbirth in women with and without history of UICA. Patients with intracranial vascular malformation and traumatic intracranial hemorrhage were excluded. The cohort of pregnant women with known history of UICA was compared with the cohort of those without history of UICA with univariate analysis.

Results:
A total of 323 patients with known history of UICA were hospitalized for childbirth compared to 13,669,848 with no history of UICA. Higher rates of intracranial hemorrhage was observed in history of UICA group compared to no history of UICA [subarachnoid hemorrhage (0.31% Vs 0.001%, p<0.01), intracerebral hemorrhage (0.94% Vs 0.001%, p<0.01), and non-specific intracranial hemorrhage (0.28% Vs 0.0004%, p<0.01)]. UICA group had higher incidence of essential hypertension (6.9% Vs 1.1%, p<0.01), pre-eclampsia (7.1% Vs 3.5%, p<0.01), and eclampsia (0.6% Vs 0.07%, p<0.01), and prevalence of smoking (8.23% Vs 3.95%, p<0.01). The rate of cesarean section (78.8% Vs 29.6%, p<0.01) and length of average hospital stay (3.76 Vs 2.57 days, p<0.01) was higher in UICA group. UICA group had higher rates of major anesthesia complications (0.32% Vs 0.01%, p<0.01), prolonged mechanical ventilation (1.2% Vs 0.04%, p<0.01), and blood transfusion (3.12% Vs 0.75%, p<0.01). 80% of UICA patients who had intracranial hemorrhage also had cesarean section.

Conclusion:
Women undergoing childbirth with known history of UICA have higher risk of intracranial hemorrhage, peripartum complications, and longer hospitalizations compared to women without a known UICA. Aggressive management of risk factors for aneurysm rupture including hypertension and smoking could potentially decrease the rupture risk. Further research is needed to understand whether delivery method has an impact on decreasing risk of rupture.
Abstract WP123: Hyperhomocysteinaemia is an Independent Risk Factors for Intracranial Aneurysms: Acase-Control Studyin a Chinese Han Population
Authors: Wang Qun , Xu Bainan
Published: January 2019

Introduction:
Intracranial aneurysms (IAs) are common lesions in the brain. There is a strong relation between hyperhomocysteinaemia (HHcy) and cerebrovascular disease, we perform a retrospective study within the Chinese Han population to investigate the association between HHcy and IAs.

Methods:
206 patients with IAs and 206 control subjects was evaluated for their serum total homocysteine levels. With multiple logistic regression analysis, the association between HHcy and the risk of IAs was estimated. Interaction and stratified analyses were conducted according to age, sex, BMI, smoking, drinking status, and chronic disease histories. The threshold effect was examined by two-piecewise linear regression model.

Results:
The multivariate logistic regression analyses revealed a significant association between HHcy and IAs (odds ratio [OR] =1.68; 95% confidence interval [CI], 1.02-2.75) after adjusting for classical vascular risk factors. And a 2% higher risk of IAs was observed, which was associated with a 1 μmol/L increase in serum total homocysteine level. The interaction analysis showed that age played an interactive role in the association between HHcy and IAs.

Conclusions:
In summary, the results of our study provide evidence that HHcy is an independent risk factor for IAs in the Chinese Han population, specially in the elderly subgroup. Considering all the findings, longitudinal studies and clinical trials of homocysteine lowering therapy by dietary or medical intervention are needed to assess the causal nature of these relationships.
Abstract WP124: Practice Variation in the Management of Aneurysmal Subarachnoid Hemorrhage- A Survey of US and Canadian Emergency Medicine Physicians
Authors: Kumar Aarti , NIknam Kian , Lumba-Brown Angela , Bledsoe Joseph , Woodruff Michael , Kohn Michael , Perry Jeff , Govindarajan Prasanthi
Published: January 2019

Introduction:
To rule out sub-arachnoid hemorrhage (SAH) national guidelines for emergency physicians recommends obtaining a non-contrast CT scan and, if negative, a lumbar puncture. However, anecdotal evidence suggests recent adoption of CT non-contrast alone in patients presenting within six hours from symptom onset and an increase in the use of a newer imaging modality, CT angiogram (CTA). Our aim was to examine emergency physicians’ diagnostic approach to SAH diagnosis and their adherence to the current guidelines.

Method:
We developed, validated, and distributed a survey to emergency physicians at three different emergency departments: Site 1) Stanford Healthcare, California, 2) Intermountain Healthcare, Utah, and 3) The Ottawa Hospital, Ottawa, Ontario. We surveyed emergency physicians with questions on test performance for SAH detection and case based scenarios to assess adherence to guidelines. Results were presented as proportions with 95% CIs.

Results:
Of the 216 physicians surveyed, we received 168 responses (77.8%). The responses by site were: 1) (n= 38, 23.2%), 2) (n=70, 42.7%), 3) (n=56, 34.1%). Most physicians indicated that non-contrast CT imaging within a 6-hour window detects >90% of SAH in those with a confirmed SAH [n=150 (
89.3%,
95%CI 83.6 - 93.5)]. In response to the case based scenarios, a majority of the physicians indicated that they would use a non-contrast CT with an additional CTA [n=110 (
65.5%,
95%CI 57.8- 72.6)], some indicated an additional LP [n=57 (33.9%, 95%CI 26.8 - 41.6)], and a few indicated both an additional CTA and LP[n=16 (9.5%, 95%CI 5.5-15.0)]. We also observed practice site variation in the proportion of physicians who indicated that they would use CTA: 1) (n=25/38, 65.8%), 2) (n= 54/70, 77.1%), and 3) (n=28/56, 50.0%) (p= 0.006).

Conclusion:
Survey responses indicated a significant variation in the emergency physicians’ use of diagnostic imaging for SAH and divergence from current guidelines. In our future studies, we will explore the reasons for the practice variation and increasing use of CTA as a diagnostic modality in SAH evaluation.
Abstract WP127: Downregulation of Estrogen Receptor Alpha Activates NLRP3 Inflammasome in a Rat Model of Intracranial Aneurysms
Authors: Yamaguchi Tadashi , Kitazato Keiko T , Shikata Eiji , Miyamoto Takeshi , Korai Masaaki , Shimada Kenji , Tada Yoshiteru , Kanematsu Yasuhisa , Takagi Yasushi
Published: January 2019

Background:
Subarachnoid hemorrhage due to the rupture of intracranial aneurysms is catastrophic. Its prevention requires a detailed understanding of its pathogenesis. Using our newly established estrogen-deficient rat aneurysm model, we found that estrogen receptors (ERs) were down-regulated, matrix metallopoteinase-9 and the tissue inhibitor of metalloproteinase-2 (MMP9/TIMP2) were imbalanced, and interleukin-1β (IL-1β) was increased in the vulnerable aneurysmal wall. As NLRP3 inflammasome activates the production of caspase1-dependent IL-1β, we focused on its role in the elicitation and rupture of intracranial aneurysms. We hypothesized that NLPR3 is mediated by ERs and associated with vascular vulnerability.

Methods:
To induce aneurysms, 10-week-old female Sprague-Dawley rats were subjected to hemodynamic changes and hypertension (HT). They were then randomized into two groups of 19 rats each. Group 1 was ovariectomized (HT-OVX
+
), group 2 was intact (HT-OVX
-
). Sham-operated rats were the control. Vascular smooth muscle cells from human brain were treated or not treated with ER-α and ER-β agonists.

Results:
During 12-week observation, aneurysms ruptured in 47% of the HT-OVX
+
and 16% of the HT-OVX
-
rats (p < 0.05). Immunohistochemically, the expression of ERα but not of ERβ was decreased, while the expression of the inflammasome components NLRP3, caspase1, IL-1β, of MMP-9, and the mRNA level of NLRP3, IL-1β and MMP-9 was increased in HT-OVX
+
rats. In human smooth muscle cells subjected to estrogen deficiency, the expression of NLRP3 was increased by angiotensin II and abrogated by the ER-α agonist but not the ER-β agonist. These findings suggest that in intracranial aneurysms prone to rupture, the activation of NLRP3, mediated by a decrease in ERα, plays a part.

Conclusion:
For a better understanding of the relationship between the rupture of intracranial aneurysms and the activation of inflammasomes under estrogen-deficient conditions, additional studies are underway.
Abstract WP134: Calcium Release-activated Calcium Channel Inhibition Improves Neurological Outcome and Suppresses Inflammation in Female Mice Following Cerebral Ischemic Injury
Authors: Mizuma Atsushi , Kacimi Rachid , Stauderman Ken , Dunn Michael J , Hebbar Sudarshan , Yenari Midori A
Published: January 2019

Purpose:
Calcium release-activated calcium (CRAC) channels activate microglia via store-operated Ca
2+
entry. We previously reported that the specific CRAC channel inhibitor (CM-EX-137) had neuroprotective effects in a model of experimental stroke due to suppression of microglial activation in male mice. However, it is well known that sex differences can influence stroke outcome as well as immune responses. Whether CRAC channel inhibition in female mice is similarly neuroprotective is unknown. The purpose of this study is to determine whether female mice respond similarly CRAC channel inhibition in a stroke model

Subjects and Methods:
C57/BL6 female mice, aged 2 months were subjected to distal middle cerebral artery occlusion (dMCAO) were treated with CM-EX-137 (5mg/kg IP; dMCAO-CM) or vehicle control (dMCAO-vehicle) daily for 3d. Stroke surgeries were carried out during the same phase of the estrus cycle (diestrus) to avoid potential confounds due to varying estrogen levels. These groups were also compared to sham groups. CM-EX-137 was injected immediately after occlusion and at 24 & 48h. Brains were extracted 3d post dMCAO. Neurological functions were evaluated before surgery, and 1 & 3d later. Lesion size was estimated from cresyl violet stains. Microglia and astrocyte activation were assessed using immunohistochemistry.

Results:
Neurological function at both 24 and 72 h post ischemia were significantly improved in dMCAO-CM group, compared with dMCAO-vehicle group (n=7/group; p<0.001). CM-EX-137 also significantly reduced infarct volume at 3dafter dMCAO (p<0.001). CM-EX-137 inhibited microglial/monocyte/macrophage activation (p<0.001; isolectin B4, CD68) and led to decreased iNOS positive cells (p<0.01). CM-EX-137 also decreased expression of CRAC channel components STIM1 and Orai1 on CD68+ macrophages (p<0.001). However, GFAP staining indicated that CM-EX-137 had no effect on astrocyte activation.

Conclusion:
CRAC channel inhibition reduce inflammatory responses and improve neurological outcome following experimental stroke in female animals. These results are in line with those that we observed in male mice. Thus, CRAC channel inhibition seems to be similarly effective and anti-inflammatory in both genders in a stroke model.
Abstract WP135: CD36 Contributes to Stroke Induced Cognitive Deficits
Authors: Balkaya Mustafa , Cho Sunghee
Published: January 2019

Introduction:
The number of preclinical studies employing long term behavioral testing is increasing. However, long-term behavioral evaluations in genetic animal models is often confounded by their acute injury severity. In addition, these studies have been primarily focused on motor outcomes despite stroke patients also suffer from a wide range of cognitive and psychiatric disturbances. The purpose of study is to investigate recovery via comprehensive behavior assessments in WT and CD36KO mice.

Methods:
Male and female mice were subjected to right transient MCA occlusion for different durations: 30 for WT and 40 min for CD36KO (N= 13/group) to normalize their injury size. A battery of tests for i) motor (rotarod, open field), ii) anxiety (plus maze, Light dark box), and iii) depression (sucrose preference, forced swim test) were performed before, and 2 weeks and 7 weeks after stroke. Cognitive function is assessed at 9 weeks using a water maze protocol consisting of a training phase, probe trial, and a visible platform relearning task.

Results:
At baseline KO animals showed reduced rotarod performance and hypoactivity. Infarct sizes were comparable between genotypes. Stroke induced hyperactivity, motor and hedonic deficit and reduced depression like behavior at 2 and 7w in WT mice. CD36 deficiency ameliorated hyperactivity, anhedonia and normalized the depressive behavior. In the water maze training and probe trial, all groups showed similar performance. However among stroke groups CD36 KO mice performed significantly better compared to WT mice at the visible platform task. (Figure)

Conclusion:
The study demonstrate that CD36 deficiency attenuates stroke-induced hyperactivity, hedonic deficit, reduced depression and relearning deficit. Strategy switching deficit observed in WT stroke animals resemble the cognitive dysexecutive syndrome observed in some stroke patients. Our findings indicate that CD36 contribute to stroke-induced cognitive deficits.
Abstract WP14: Association Between Socioeconomic Status and Endovascular Therapy Among Medicare Beneficiaries With Acute Ischemic Stroke
Authors: Al-Kawaz Mais N , Merkler Alexander E , Lerario Michael P , Navi Babak B , Kamel Hooman
Published: January 2019

Introduction:
Mechanical thrombectomy has recently been proven to improve outcomes in selected patients with acute ischemic stroke, prompting concerns about equitable access to this treatment.

Methods:
We performed a retrospective cohort study using inpatient and outpatient claims between 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients who were ≥65 years old and hospitalized with ischemic stroke, defined by validated
ICD-9-CM
diagnosis codes. Our exposure variable was county-level socioeconomic advantage, defined by a validated summary score of income, wealth, education, and occupation data from the U.S. Census Bureau’s American Community Survey. Our outcome was mechanical thrombectomy, ascertained using
CPT
codes. Multiple logistic regression was used to evaluate the association between socioeconomic status and thrombectomy while adjusting for demographics, vascular risk factors, Charlson comorbidities, calendar year, intravenous thrombolysis, and mechanical ventilation (included as proxy for stroke severity).

Results:
Among 66,989 patients with acute ischemic stroke, the 459 (0.69%; 95% CI 0.62-0.75%) patients who underwent thrombectomy during their index hospitalization were younger (77.7 versus 79.9 years), more often had atrial fibrillation (65.1% versus 37.7%), and more often received intravenous thrombolysis (43.7% versus 4.5%). The likelihood of thrombectomy increased across increasing quartiles of the county-based socioeconomic advantage score: 0.46%, 0.59%, 0.70%, and 0.97% (
P
<0.001) (Figure). In an adjusted model, socioeconomic advantage was associated with thrombectomy (OR per SD, 1.05; 95% CI 1.02-1.07).

Conclusions:
We found an association between increasing socioeconomic status and higher odds of thrombectomy for acute ischemic stroke.
Abstract WP143: Acute Treatment With Purinergic Receptor P2X4 Inhibitors Show Neuroprotective and Neuro-Rehabilitation Potential in Ischemic Stroke
Authors: Verma Rajkumar , Srivastava Pranay , Cronin Chunxia G , Scranton Victoria , Jacobson Kenneth A , Liang Bruce T
Published: January 2019

Introduction:
Stroke remains a leading cause of disability in the United States. Despite recent advances, interventions to reduce damage and enhance recovery after stroke is lacking. Therefore, validating new drug targets is critical for stroke treatment. P2X4, a receptor for adenosine triphosphate ATP, regulate activation of myeloid immune cells (both infiltrating monocytes/macrophages and brain-resident microglia) after stroke injury. Over-stimulation of P2X4Rs, due to excessive ATP release from the dying or damaged neuronal cells, contributes to ischemic injury. In this study, we pharmacologically targeted P2X4R to control immune response of myeloid cells during acute stroke phase and studied recovery at acute or chronic time point after stroke.

Methods:
We subjected 8-12 weeks old wild type mice of both sexes to 60 min right middle cerebral artery occlusion (MCAo) followed by 3 (acute) or 30 (chronic) days of reperfusion. We performed histological, behavioral (sensorimotor, anxiety and depressive), and flow cytometric analyses to determine the acute and chronic outcomes after P2X4R inhibitor 5-BDBD (1mg/kg P.O daily x3 days started after 4 hrs. of MCAo) treatment.

Results:
Treatment with 5-BDBD for 3 days not only significantly (*P<0.05) reduced infarct volume (40.94 ± 7.512 N=7 vs 21.21 ± 7.372 N=11, unpaired t-test) and neurological deficit (ND) score at 3 days post-stroke but also showed a progressive recovery on motor and balance coordination using rotarod test (*P<0.05) during chronic recovery at 30 days. 5-BDBD treatments also improved (*P<0.01) anxiety like behavior during the chronic recovery. We did not see any effect on depression like behavior. Flow cytometric analysis reveals that 5-BDBD treatment significantly reduced (*P<0.05) total number of infiltrated leukocytes. Subsequent analysis revealed that among those infiltrated leukocytes the number of Ly6C
+hi
pro-inflammatory monocytes was reduced in 5-BDBD vs. vehicle treated mice.

Conclusions:
Acute P2X4R inhibition protects against ischemic injury at both acute and chronic time point after stroke. Reduced number of infiltrated Ly6C
+hi
proinflammatory monocyte in 5-BDBD treated mice suggests its potential mechanism of neuroprotection after stroke.
Abstract WP147: Influence of White Blood Cell Count on Outcome for Thrombolysis-Treated Acute Ischemic Stroke ENCHANTED Post HocAnalysis
Authors: Yang Jie , Lin Yapeng
Published: January 2019

Background:
Increased inflammatory reaction can aggravate brain injury after acute ischemic stroke, but the clinical effect of such response is not fully understood. The aim of this study was to determine associations of peripheral white blood cell (WBC) count on clinical outcome among participants of the ENCHANTED study.

Methods:
Data are from the Enhanced Control of Hypertension for < and > for > Thrombolysis Stroke Study (ENCHANTED), aninternational, multicenter, randomized controlled trial where patients with acute ischemic stroke were randomized to low-dose (0.6 mg/ kg) or standard-dose (0.9 mg/kg) IV alteplase.Blood samples were collected on admission < for < and > for > WBC count was measured at local laboratories. The primary outcome was death or disability, defined by scores 3–6 on the modified Rankin Scale at 90 days.Secondary outcomes included ordinal mRS shift,fatal intracerebral hemorrhage(ICH) by various standard criteria.Associations of baseline WBC count < for < and > for > outcomes were evaluated in logistic regression models.

Results:
There were 3179 participants with relevant data who were classified into quartiles of WBC counts (≤ 6.30, 6.31–7.82, 7.83–9.80, < for < and > for > ≥ 9.81х109/L, respectively).Increased WBC count was associated with younger age,elevated NIHSS scores, less antithrombotic used,elevated heart rate,elevated fever treated,stroke severity.

Risks of death or major disability at 90 days increased progressively with higher WBC count: frequencies of 30.4%, 34.7%,39.1% < for < and > for > 44.8% for quartile groups, respectively (P <.0001 for trend). After adjustment for baseline clinical < for < and > for > imaging variables including age, sex, body temperature, systolic BP, heart rate, high NIHSS scores, < for < and > for > randomized treatment, the association between WBC count < for < and > for > primary outcome was still significant (P <.0001 for trend).

Conclusions:
Elevated WBC count on admission may be an independent prognostic predicator in patients with Acute Ischemic Stroke, but this requires further evaluation in a prospective cohort study.
Abstract WP148: ApoA-I Mimetic Peptide Reduces Vascular and White Matter Damage After Stroke in Type 2 Diabetic Mice
Authors: Wang Xiaohui , Li Rongwen , Zacharek Alex , Landschoot-Ward Julie , Chopp Michael , Chen Jieli , Cui Xu
Published: January 2019

Diabetes mellitus leads to a higher risk of ischemic stroke and worse functional outcome compared to the general population. We investigate whether L-4F, an economical apolipoprotein A-I mimetic peptide, reduces neurovascular and white matter damage in a clinically relevant stroke model using type-2 diabetic (T2DM) db/db mice.

Methods:
Adult male db/db mice were subjected to 2h middle cerebral artery occlusion (MCAo) and were orally administered saline (n=52) or L-4F (16mg/kg, n=34) with treatment initiated 2h after stroke and continued daily until sacrifice 4 days after MCAo. Mouse-brain endothelial cells, primary arterial cells derived from the aorta of C57BL/6 mice 1 day after MCAo, and primary cortical neurons derived from E15 C57BL/6-embryos were employed. These cells were subjected to high glucose conditions to simulate diabetes. L-4F treatment of T2DM-stroke mice exhibited reduced hemorrhage/infarct volume and mortality rate, as well as improved neurological functional outcome 4 days after MCAo compared with vehicle control T2DM-stroke mice (p<0.05, n=11/group); L-4F treatment also decreased BBB leakage and white matter damage measured by Belshowsky silver stained axons, Luxol Fast Blue stained myelin, SMI31 immunostained phosphorylated neurofilament and platelet derived growth factor receptor α immunostained oligodendrocyte-progenitor cells, and increased arteriolar diameter and smooth muscle cell number in the ischemic brain (p<0.05, n=11/group). Moreover, the proinflammatory mediator high mobility group box 1 and advanced glycation end product receptor, and the cerebral hemorrhage factors plasminogen activator inhibitor-1 and Annexin II were decreased in the ischemic brain in L-4F treatment T2DM-stroke mice. In vitro, L-4F treatment did not increase capillary-like tube formation in the mouse-brain endothelial cells cultured with high glucose medium. However, L-4F treatment increased primary artery cell migration, and enhanced neurite outgrowth after 2h of oxygen-glucose deprivation and axonal outgrowth in high glucose condition.

Conclusion:
This study suggests that early use of L-4F may provide a potential strategy to reduce neuroinflammation and reduce vascular and white matter damage in T2DM stroke patients.
Abstract WP160: The Effect of Type II Diabetes on Neural Differentiation and the Transcriptome Landscape of the Neurogenic Zones Following Ischemic Stroke
Authors: Rabiller Gratianne , Kanoke Atsushi , Omadaka Shunsuke , Liu Jialing
Published: January 2019

Introduction:
Previously we found that middle aged mice with type 2 diabetes (T2DM) exhibited a significant reduction in neurogenesis during baseline and after ischemic stroke compared to age-matched control mice. The current study sought to determine how T2DM affected neural differentiation and delineate the molecular mechanisms involved in the impaired neurogenesis.

Hypothesis:
We hypothesize that T2DM alters neural differentiation and signaling pathways regulating neurogenesis.

Methods:
Stroke was induced by distal middle cerebral artery occlusion (dMCAO) in young (28-31 wks, n=36) and middle-aged (53-75 wks, n=52) db/+ or db/db mice. Mice were injected with BrdU i.p. at 50 mg/kg twice daily from ds 4-7 after dMCAO and euthanized 2 wks later. Double immunofluorescent staining for BrdU and lineage markers was performed and examined by confocal microscopy to determine the fate of the new progenies in the progenitor cell (NPC) zones. To define the transcriptome landscape of the NPCs of the middle aged mice subjected to dMCAO or sham surgery, we performed single cell RNA sequencing (scRNAseq) analysis of SVZ and DG cells using the 10X genomics platform.

Results:
A significant decrease in cell proliferation and immature neurons began as early as 200 ds of age in the db/db mice compared to db/+ mice, in both naïve and MCAO mice. The percentage of surviving newborn cells expressing GFAP was increased whereas neuronal differentiation decreased in the db/db compared to db/+ middle-aged mice. The gene expression patterns in individual cells from the neurogenic zones were considerably heterogenous. T2DM and MCAO induced unique sets of upregulated or downregulated genes, despite some overlaps. Gene ontology analysis revealed a significant enrichment of differentially expressed genes associated with inflammation, adipokine and neural development.

Conclusions:
Our scRNAseq data provided the first glimpse of the genes differentially expressed under conditions of diabetes and stroke. Ongoing investigations will characterize the molecular pathways through which neurogenesis is impacted in db/db mice.
Abstract WP161: Computational Fluid Dynamics Using SAMMPRIS CT Angiography Quantifies Pro-Atherogenic Shear Stress Linked With Post-Stenotic Flow Vortices
Authors: Liebeskind David S , Wefers Daniel , Honda Tristan , Scalzo Fabien , Cotsonis George A , Cloft Harry J , Zaidat Osama O , Fiorella David J , Derdeyn Colin P , Chimowitz Marc I , Feldmann Edward , Kaneko Naoki , Hinman Jason D ,   for the SAMMPRIS Investigators
Published: January 2019

Background:
Low wall shear stress (LSS) is an established cause of pro-atherogenic endothelial pathophysiology, yet it has never been demonstrated in the cerebral circulation affected by intracranial atherosclerotic disease (ICAD). Noninvasive CT angiography (CTA) computational fluid dynamics (CFD) enables high-resolution investigation of detailed post-stenotic phenomena. We used all available CTA data in the SAMMPRIS trial of ICAD to detect and quantify post-stenotic LSS.

Methods:
CTA source images from SAMMPRIS were reconstructed in 3D followed by geometry refinements to generate a mesh of the diseased arterial lesion and adjacent segments. CFD was performed with Ansys (ICEM, Fluent), applying reference boundary conditions with k-omega turbulence and non-Newtonian modeling of the traversing blood viscosity. 3D CFD parameter maps illustrated velocity, velocity swirling and corresponding wall shear stress.

Results:
144 subjects enrolled in SAMMPRIS had CTA at baseline, including 140 with CTA source images enabling CFD. Post-stenotic velocity profiles revealed vortices in all cases, quantified by swirling and turbulent kinetic energy. These luminal flow changes were adjacent to focal regions of LSS in the post-stenotic region (Figure).

Conclusions:
Low wall shear stress is associated with vortices of fluid flow in CTA CFD modeling of ICAD from SAMMPRIS. CTA source images may be used to noninvasively quantify LSS and model this pro-atherogenic factor in ICAD across a wide variety of lesions. Future studies should examine the related endothelial biology and potential link with plaque evolution.