bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 103: Intensive versus Guideline Antiplatelet Therapy in Patients With Transient Ischaemic Attack: Data From the Triple Antiplatelets for Reducing Dependency in Ischaemic Stroke (TARDIS) Trial
Authors: Woodhouse Lisa J , Flaherty Katie , Havard Diane , Sprigg Nikola , Bath Philip M
Published: October 2018

Background:
The risk of recurrence following an ischaemic stroke (IS) or transient ischaemic attack (TIA) is high, especially immediately after the event. Intensive treatment might be more effective in preventing recurrence than guideline therapy providing bleeding does not become excessive. We tested this in a subgroup of patients enrolled with TIA into the TARDIS trial.

Methods:
TARDIS was an international multicentre prospective randomised open-label blinded-endpoint controlled trial. Patients with acute non-cardioembolic IS or TIA were randomised to intensive antiplatelet therapy (combined aspirin, clopidogrel and dipyridamole) or guideline antiplatelets (clopidogrel alone, or combined aspirin and dipyridamole) given for one month. The primary outcome was recurrent cerebral events and their severity (using modified Rankin Scale) at 3 months. Data are number (%), mean (standard deviation, SD) or odds ratio (OR) with 95% confidence interval (CI).

Results:
Of 3,096 patients, 953 (30.8%; intensive 480, guideline 473) were enrolled with TIA. At baseline: mean age 70 (SD 10); male 62%; onset to randomisation <12 hours 17%, <24 hours 48%. By day 90, no differences were present between the two treatment groups for the primary outcome, death or other functional outcomes. However, patients in the intensive arm were less likely to suffer a recurrent TIA than those on guideline treatment (OR 0.48, 95% CI 0.25-0.93).

Conclusion:
Patients with a qualifying event of TIA were less likely to suffer a recurrent TIA if they received intensive treatment rather than guideline. However, no differences were present for recurrent stroke events.
Abstract 106: Collateral Circulation in Thrombectomy for Stroke Beyond 6 Hours: Dawn Collaterals
Authors: Liebeskind David S , Xiang Bin , Jadhav Ashutosh J , Jovin Tudor G , Haussen Diogo C , Budzik Ronald F , Bonafe Alain , Bhuva Parita , Yavagal Dileep R , Hanel Ricardo A , Ribo Marc , Cognard Christophe , Sila Cathy , Hassan Ameer E , Smith Wade S , Saver Jeffrey L , Nogueira Raul G ,   for the DAWN Investigators
Published: October 2018

Background:
Collaterals govern the pace and severity of cerebral ischemia, distinguishing fast or slow progressors and corresponding therapeutic opportunities. The fate of sustained collateral perfusion or collateral failure is poorly characterized without arterial revascularization. We characterized the nature and impact of collaterals in the late time window for thrombectomy established in DAWN.

Methods:
The DAWN Imaging Core Lab prospectively scored collateral grade on baseline CTA and DSA (endovascular arm only), blinded to all other data. CTA collaterals were graded with the Tan scale and DSA collaterals were scored by ASITN grade. Descriptive statistics characterized CTA collateral grade in all DAWN subjects and DSA collaterals in the endovascular arm. The relationship between collateral grade and day 90 outcomes was separately analyzed for each treatment arm.

Results:
Collateral circulation to the ischemic territory was evaluated on CTA (n=144; median 2, 0-3) and DSA (n=57; median 2, 1-4) before thrombectomy in 161 DAWN subjects (mean age 69.8 ± 13.6 years; 55.3% women; 91 endovascular therapy, 70 control). CTA revealed a broad range of collaterals (grade 3=100%, n=64; 2=50-99%, n=45; 1=0-49%, n=31; 0=0%, n=4). DSA also showed a diverse range of collateral grades (grade 4, n=4; 3, n=22; 2, n=27; 1, n=4). Across treatment arms, baseline demographics, clinical variables except AF (41.6% endovascular vs. 25.0%, p=0.04) and CTA collateral grades were balanced. More robust CTA collateral grade was linked with lower baseline NIHSS (r=-0.25; p=0.003), smaller core infarct volumes (r=-0.36, p<0.001) and better day 90 mRS 0-2 clinical outcomes (r=0.20, p=0.019), but was unrelated to time from symptom onset or last known well to thrombectomy. Higher DSA collateral grade was linked with lower baseline NIHSS (r=-0.32; p=0.015), but sample size limited other potential associations. Interestingly, collateral grades on CTA and DSA were highly correlated (r=0.88, p<0.001).

Conclusions:
DAWN subjects enrolled at 6-24 hours after onset with small infarct cores had a wide range of collateral grades on both CTA and DSA. In this late time window, better collaterals manifest milder stroke severity at baseline, smaller infarct cores and better clinical outcomes.
Abstract 107: Real World Clinical and Radiographic Outcomes With and Without Intravenous tPA in Anterior Circulation Large Vessel Occlusion Mechanical Thrombectomy Patients Treated Within 8 Hours
Authors: English Joey , Veznedaroglu Erol , Liebeskind David S , Budzik Ronald F , Baxter Blaise , Krajina Antonin , Shields Ryan , Sarraj Amrou , Nogueira Raul , Malek Ali , Gupta Rishi ,   Trevo Retriever Registry Investigators
Published: October 2018

Background and Aims:
Intravenous tPA remains the standard of care, with MT currently indicated within 8 hours for IV tPA failures or patients with IV tPA contraindications. Whether LVO patients should receive IV tPA treatment or instead be triaged directly to MT therapy is currently unknown but greatly debated. The Trevo Registry is a real world, multi-center, international study of mechanical thrombectomy (MT) patients treated from 0-24 hours. Evaluation of the Trevo Registry clinical and procedurals outcomes of MT patients treated with or without IV tPA could provide insight into the benefit of IV tPA in MT patients. We hypothesized that in MT patients treated within 8 hours, pretreatment with intravenous tPA would lead to better clinical outcomes compared to patients who did not receive IV tPA.

Method:
Consecutively enrolled patients treated within 8 hours with ICA, M1, or M2 occlusions were selected for analysis. Univariate and multivariable regressions were conducted to identify clinical and radiographic independent variables that correlate best with the dependent variable of functional outcome: mRS 0-2, with a focus on intravenous tPA treatment.

Results:
A total of 1183 Trevo Registry patients (overall enrolled, n=2010) qualified for analysis, of whom 380 were not treated with IV tPA. Demographics were similar, however atrial fibrillation (46.3% vs 27.2%) and previous ischemic stroke (14.1% vs 7.5%) were higher in the no IV tPA group. The median time to treatment was similar (3.8 vs. 3.6 hrs). First pass mTICI ≥ 2B (63.6% vs 66.4%) and final revascularization (91.1% vs 92.8%) were similar between no IV tPA and IV tPA groups.Unadjusted, there were similar rates of functional outcome (90 day mRS 0-2; 60.9% vs. 62.5%). After adjustment, patients who did not receive IV-tPA had similar rates of good outcome (aOR 1.08, 95% CI [0.87-1.34]. P=0.58) as well as reduction (shift) in disability (aOR 1.08, 95% CI [0.87-1.34]. P=0.49). Safety outcomes (mortality, sICH) were similar between both groups.

Conclusion:
In the Trevo Registry of MT patients treated within 8 hours, patients who did not receive IV tPA had similar endovascular and clinical outcomes as patients pretreated with IV tPA. The added benefit of IV tPA for MT patients should be further investigated.
Abstract 113: CT Perfusion Mismatch Identifies More Thrombectomy Patients Than Clinical Core Mismatch
Authors: Rodrigues Edrich J , Yassi Nawaf , Yan Bernard , Mitchell Peter J , Dowling Richard , Bush Steven , Sharma Gagan , Pesavento Lauren , Hand Peter , Davis Stephen , Campbell Bruce
Published: October 2018

Background:
Following DAWN and DEFUSE 3, optimal imaging selection of large vessel ischemic stroke patients for thrombectomy >6h is important. We hypothesized that perfusion mismatch used in EXTEND-IA and DEFUSE 3 would identify more patients eligible for thrombectomy than clinical-core mismatch used in DAWN.

Methods:
Prospectively collected data were analyzed for acute ischemic stroke patients aged>18 with pre-treatment whole brain CT perfusion from 2012-2017 at a comprehensive stroke center. CTP was omitted >6h in patients with extensive CT hypodensity. We compared the proportion of patients with anterior circulation large vessel occlusion (ICA, M1 and tandem occlusions) who fulfilled criteria for DAWN (clinical-core mismatch: age<80 & NIHSS≥20 with <51mL core, age<80 & NIHSS10-19 with <31mL core, age>80 & NIHSS>10 with<21mL core), DEFUSE3 (mismatch ratio>1.8, mismatch>15mL, core<70mL, age<91, NIHSS>5) and EXTEND-IA (mismatch ratio>1.2, mismatch>10mL, core<70mL, no age or NIHSS limits). Pre-morbid function, alteplase eligibility and tandem occlusion trial exclusions were not applied to emulate clinical practice. Independent functional outcome was defined as 90 day mRS 0-2.

Results:
Of 982 ischemic stroke patients evaluated with pre-treatment CTP, 291 had large vessel occlusion. Within 6h of stroke onset, 175/231 (76%) patients met EXTEND-IA criteria compared to 153/231 (60%) DEFUSE3 and 96/231 (42%) DAWN, p<0.0001 for all comparisons. Beyond 6h after onset, 39/58 (67%) met EXTEND-IA mismatch criteria compared to 33/58 (57%) DEFUSE 3 criteria and 26/58 (45%) DAWN criteria, p<0.0001 for all comparisons. Overall 4 patients with clinical-core mismatch did not meet perfusion mismatch criteria. Patients eligible for DEFUSE3 but not DAWN achieved independence in 48% vs 40% in those eligible for both studies, OR 2.1 95%CI 0.9-5.0, p=0.09 in logistic regression adjusted for age and NIHSS. Similar findings applied to patients eligible for EXTEND-IA but not DAWN.

Conclusions:
Perfusion mismatch selection would lead to substantially more patients receiving thrombectomy than clinical-core mismatch. These patients were generally older with milder NIHSS, but had similar probability of independent outcomes.
Abstract 114:
Aspects
versus Perfusion in the Trevo Retriever Registry: Defining the Core on the Largest Scale to Date
Authors: Liebeskind David S , Zhang Yanchang , Trieu Harry , Revanur Anjali , Scalzo Fabien , Veznedaroglu Erol , English Joey , Baxter Blaise W , Budzik Ronald F , Bartolini Bruno M , Krajina Antonin , Malek Ali , Sarraj Amrou , Gupta Rishi , Jadhav Ashutosh J , Jovin Tudor G , Nogueira Raul G ,   for the Trevo Retriever Registry Investigators
Published: October 2018

Background:
Routine use of advanced imaging versus ASPECTS for imaging triage of endovascular thrombectomy candidates has not been evaluated on a large scale to date. Ischemic core may be defined by ASPECTS or perfusion imaging, yet these variable definitions likely reflect different pathophysiology as perfusion may fluctuate and ASPECTS lesions may be time-dependent.

Methods:
The Trevo Retriever Registry was a prospective, open-label, consecutive enrollment, multicenter, international registry with more than 65 enrolling sites worldwide. The Imaging and Angiography Core Lab systematically adjudicated more than 1,500 subjects, scoring ASPECTS and separately processing perfusion imaging. Ischemic core volume on perfusion imaging was defined as rrCBF<30% (CTP) and analyzed with respect to ASPECTS.

Results:
488 subjects (68.3±14.4 years; 53.3% women; baseline NIHSS median 15 (10-19) with anterior circulation occlusions were evaluated with both ASPECTS and perfusion imaging prior to thrombectomy. Arterial occlusions included 87/487 (17.9%) ICA and 296/487 (60.8%) proximal M1 MCA, treated with thrombectomy at median 4.7 (3.3-7.9) hours from time last known well (TLKW). ASPECTS was median 8 (7-9) with ischemic core lesions of median 18 (4.9-39.2) cc. At-risk hypoperfusion (Tmax>6s) lesions were median 109.8 (62-156.9) cc. TLKW was associated with ASPECTS (r=-0.18, p<0.001) yet no time relationship was noted with either ischemic core or at-risk hypoperfusion on perfusion imaging. ASPECTS correlated modestly with perfusion imaging-derived ischemic core (r=-0.35, p<0.001) and at-risk hypoperfusion (r=-0.24, p<0.001). Post-procedure mTICI≥2b occurred in 448/488 (91.8%). Each increment in baseline ASPECTS was associated with an adjusted OR of 1.21 (95%CI (1.05-1.39), p<0.008 for good clinical outcomes (day 90 mRS 0-2), whereas the perfusion lesion volume for ischemic core and at-risk hypoperfusion did not predict outcomes.

Conclusions:
Largescale, systematic evaluation of ASPECTS and perfusion imaging prior to thrombectomy reveals discrepancy in the definition of ischemic core and the prediction of clinical outcomes after revascularization. ASPECTS is time-dependent, yet reliably predicts outcomes in routine clinical practice.
Abstract 117: One Stop Management of Acute Stroke Patients: Minimizing Door to Groin Times and Improving Functional Outcome
Authors: Psychogios Marios-Nikos , Behme Daniel , Tsogkas Ioannis , Maier Ilko L , Hesse Amélie C , Liebeskind David S , Bähr Mathias , Knauth Michael , Liman Jan
Published: October 2018

Introduction:
Intrahospital time delays significantly affect neurological outcome of stroke patients with large vessel occlusion. Conventional imaging prior to thrombectomy leads to time delays. We report the 100 first consecutive (mothership and transfer) patients triaged in our department with a one stop management, based on flat detector CT (FDCT) and FDCTA.

Methods:
In this observational study, we transported stroke patients with an NIHSS ≥ 7 directly to the angio suite, bypassing multidetector CT. Multimodal imaging consisted of noncontrast FDCT and biphasic FDCTA. Patients with large vessel occlusion remained on the angio table and were treated with intravenous rtPA, if no exclusion criteria were present, and thrombectomy; peripheral occlusions were treated with intravenous rtPA; intracranial hemorrhage and stroke mimics were treated as per guidelines. Intrahospital times as well as outcomes were recorded and compared to past patients with a case-control analysis, matched for age, admission NIHSS, ASPECTS and symptom-to-door time.

Results:
One-hundred consecutive patients were transferred directly to our angio suite. Mean age was 77 (IQR 69-83). Symptom onset to admission time was 137 min (IQR 70-187). Ischemic stroke was diagnosed in 79 patients, intracranial hemorrhage was present in 11 and Todd`s paresis in 10 patients. We recorded a median door-to-groin time of 25 min (IQR 19-29) and door-to-reperfusion time of 68 min (IQR 53-89). Compared to patients triaged with multidetector CT, we observed a highly significant reduction of door-to-groin times (60 min (95% CI 54-65) to 25 min (95% CI 21-26); P<0.001). Median mRS at 90 days was lower in the FDCT group (MDCT group 4 (95% CI 3-5) to FDCT group 2 (95% CI 2-4); P=0.168). Mortality (21 vs. 23%), sICH (7 vs. 5%) and any hemorrhage (25% vs. 17%) rates were comparable.

Conclusions:
One stop management is feasible for stroke triage and results in reduction of intrahospital times and improved functional outcomes.
Abstract 121: Embolic Stroke of Unknown Source is Associated With Higher Left Atrial Fibrosis Than Other Stroke Subtypes
Authors: Majersik Jennifer J , Tirschwell David L , Longstreth W T , Wilson Brent D , Marrouche Nassir F , Akoum Nazem
Published: October 2018

Introduction:
Atrial cardiomyopathy without atrial fibrillation is suspected to lead to embolic stroke of unknown source (ESUS). Late gadolinium enhancement cardiac MRI (LGE-MRI) is a non-invasive technique used to assess atrial fibrosis and cardiomyopathy.

Hypothesis:
We hypothesized that patients with ESUS have a higher percent of atrial fibrosis, quantified using LGE-MRI, compared to other stroke subtypes.

Methods:
Cardiac LGE-MRIs were obtained in ischemic stroke patients treated at two comprehensive stroke centers. Acquisition of images took approximately 30 minutes and was well tolerated by all of the patients. Each patient had a complete standard of care evaluation. Stroke neurologists blinded to LGE-MRI results characterized the stroke subtypes according to TOAST methods modified by the addition of ESUS to the cryptogenic category. Atrial enhancement was defined on LGE-MRI by an intensity threshold that was determined by expert inspection with initial visualization via a volume-rendering tool and expressed as a percentage. We used a t-test to compare mean percent atrial fibrosis between ESUS and non-ESUS patients.

Results:
We enrolled 17 patients: 3 (17%) female; mean age 53 years (SD 16); and 10 (59%) with ESUS. Age and sex did not differ between ESUS and non-ESUS patients. Atrial fibrosis estimation by LGE-MRI was successfully quantified in all patients. Mean left atrial fibrosis for the entire sample was 9.8% (SD 7.9) and was significantly higher in ESUS (14.1%, SD 6.6%) versus non-ESUS patients (3.6%, SD 5.2%), p=0.003. See Figure.

Conclusions:
Compared to non-ESUS stroke patients, ESUS patients had significantly higher percentages of atrial fibrosis, supporting atrial cardiomyopathy as one possible mechanism for ESUS. Larger sample sizes are needed to confirm that LGE-MRI is a useful tool to reduce uncertainty about the cause of stroke in the ESUS population.
Abstract 126: Relationship Between Visceral Infarction and Ischemic Stroke Subtype
Authors: Finn Caitlin B , Hung Peter , Patel Praneil , Gupta Ajay , Kamel Hooman
Published: October 2018

Background:
Most cryptogenic strokes are thought to have an embolic source. We sought to determine whether visceral infarcts, which are usually embolic, are associated with cryptogenic stroke.

Methods:
Among patients prospectively enrolled in the Cornell AcutE Stroke Academic Registry (CAESAR), we selected those with a contrast-enhanced abdominal computed tomography (CT) scan within 1 year of admission. Our primary predictor was stroke subtype, as adjudicated per the TOAST classification. Our outcome measure was renal or splenic infarction, as assessed by a single radiologist blinded to stroke subtype. We used Fisher’s exact test and multiple logistic regression to compare the prevalence of visceral infarcts among patients with cardioembolic stroke, stroke of undetermined etiology, and non-cardioembolic stroke (large- or small-vessel stroke).

Results:
Among 227 patients with a contrast-enhanced abdominal CT scan, 59 had a visceral infarct (35 with renal infarcts and 27 with splenic). The prevalence of visceral infarction was significantly different among patients with cardioembolic stroke (34.2%; 95% confidence interval [CI], 23.7-44.6%), stroke of undetermined etiology (23.9%; 95% CI, 15.0-32.8%), and stroke from large-artery atherosclerosis or small vessel-occlusion (12.5%; 95% CI, 1.8-23.2%)
(P
= 0.03). In multiple logistic regression models adjusted for demographics and vascular risk factors, we found significant associations with visceral infarction for both cardioembolic stroke (odds ratio [OR], 3.5; 95% CI, 1.2-9.9) and stroke of undetermined source (OR, 3.3; 95% CI, 1.1-10.5) as compared with the reference group of non-cardioembolic strokes.

Conclusions:
The prevalence of visceral infarction differs significantly across ischemic stroke subtypes. Cardioembolic and cryptogenic strokes were associated with a higher prevalence of visceral infarcts than non-cardioembolic strokes.
Abstract 14: Significantly Reducing Stroke Door to Needle Times through Stroke Nurse Facilitators and Administering Bolus in CT
Authors: Cullen Sarah , Squires Shane , Spears Joy , Amin Rali , Cohen Daniel
Published: October 2018

Background and Issues:
Eliminating treatment delays for acute ischemic stroke patients to meet the national door to needle (DTN) Target Stroke Phase II goals continues to present a challenge for many facilities. Although the Stroke Alert process is usually guided by strict protocols it can still suffer delays from a lack of communication and facilitation to ensure rapid patient assessment and treatment.

Purpose:
The purpose of this project was to eliminate Stroke Alert delays related to communication and lack of facilitation by implementing a Stroke Nurse Facilitator (SNF) and allow intravenous tissue plasminogen activator (tPA) to be successfully started in the CT room.

Methods:
An interdisciplinary team conducted a Pareto analysis on DTN delays and found communication to be the most common. Communication was also felt to be the biggest barrier to starting tPA in the CT room. The role of a SNF was created and mapped into the Stroke Alert process to overcome these barriers. The role launched in November 2016. Six months later, after the role became an integral part in the Stroke Alert process, the team moved forward with administering tPA in the CT room as part of the process.

Results:
DTN was measured in 61 emergency department stroke patients, 34 in the pre-intervention, 12 in the SNF only, and 15 in the SNF and tPA in CT groups. Data were analyzed using the non-parametric Mann Whitney U test. Although not statistically significant due to the small sample size, there was a large improvement in DTN from pre (n=34) to the first intervention group [Z= 11.19, p=.06, d =.84]. The improvement from DTN from pre to the second intervention group was very large and statistically significant [Z= 24.00, p<.001, d = 1.34]. There was no statistically significant difference in the outcome between the two post groups. The total difference between pre and post samples was large and statistically significant (t=4.46, p<.001, d = 1.10).

Conclusions:
Successful communication and facilitation is crucial to achieve positive outcomes or process improvements. Implementing a SNF to overcome these barriers could prove to be a successful strategy to improving DTN times for acute stroke patients.
Abstract 142: Transgenic Overexpression of Krüppel-Like Factor 11 in Endothelium Ameliorates Ischemic Brain Injury
Authors: Tang Xuelian , Liu Kai , Hamblin Milton H , Xu Yun , Yin Ke-Jie
Published: October 2018

Introduction:
Krüppel-like factors (KLFs) belong to zinc finger family of transcription factors and their roles in stroke are poorly explored. KLF11 is highly enriched in vascular endothelium, and we have previously documented that peroxisome proliferator-activated receptor gamma-mediated cerebral protection during ischemic insults needs KLF11 as a critical coactivator. However, the role of endothelial KLF11 itself in cerebrovascular function and stroke outcome is unclear.

Hypothesis:
We hypothesize that endothelium-targeted overexpression of KLF11 stabilizes the BBB, reduces the progression of brain damage, and improves neurological outcomes after ischemic stroke.

Methods:
Transient middle cerebral artery occlusion was performed in endothelial cell-selective KLF11 transgenic mice (EC-KLF11 Tg), and WT controls. BBB integrity was assessed by using Evans Blue and TMR-Dextran extravasation assays. Brain water content was measured by using a dry-wet method. Brain infarct was analyzed by 2%TTC staining. A battery of neurobehavioral tests, including rotarod, adhesive tape removal, and foot fault, were performed to assess sensorimotor functions. Total RNA was extracted from brain tissues and the expression of BBB tight junctions (TJs) was detected by qPCR and western blotting.

Results:
Compared to WT controls, EC-selective transgenic overexpression of KLF11 led to reduced BBB leakage in ischemic brains, evidenced by significantly reduced extravasation of BBB tracers and less brain water content. EC-KLF11 Tg mice also exhibited a smaller brain infarct and improved neurological functions in response to ischemic insults. Mechanistically, we found KLF11 binding sites in the promoter region of major endothelial TJs including Claudin 5 and ZO-1. EC-selective transgenic overexpression of KLF11 significantly increased cerebral TJ levels in mice after ischemic stroke.

Conclusions:
The present study has demonstrated that KLF11 functions at the EC level to preserve BBB structural and functional integrity and confers brain protection in ischemic stroke. KLF11 may be a novel therapeutic target for the treatment of ischemic stroke.
Abstract 143: Stroke Impairs Endothelial Cells Through Downregulation of Programed Death Ligand-1 Expression
Authors: Lai Yun-Ju , Sun Ping , Chauhan Anjali , Patrizz Anthony , Lee Juneyoung , Li Jun , Li Chia-Wei , Venna Venugopal R , Kofler Julia , McCullough Louise D
Published: October 2018

Introduction:
Stroke triggers a robust inflammatory response, allowing leukocytes to cross the blood brain barrier. T cells infiltrate in an antigen-independent manner early after injury, leading to additional neuronal injury. The pro-inflammatory cytokine, interferon-gamma (IFNγ), upregulates programed death ligand-1 (PD-L1) expression. Engagement of PD-L1 and programed death-1 (PD-1) “calls off” the cytolytic activity of infiltrated T cells. The immunosuppressive activity of PD-L1 is modulated by ubiquitination and glycosylation. Glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces degradation of PD-L1. To date, the role of PD-L1 in endothelial cells (ECs) remains elusive.

Hypothesis:
PD-L1 in EC reduces neuroinflammation via protection of microvascular integrity.

Methods:
Human brain ECs, HBEC-5i, were subjected to IFNγ treatment in normal or oxygen-glucose deprivation (OGD) conditions. Western blot, Fluorescence-activated cell sorting analysis, PD-1 binding assays and an
in vitro
T cell killing assay were performed to investigate EC viability and PD-L1 function. Male mice (12 weeks) were subjected to a 60-minute middle cerebral artery occlusion (MCAO) and given either vehicle or GSK3β inhibitor VIII (4 mg/kg). We examined PD-L1 expression, blood vessel integrity and T cell activation in brain tissue using anti-PD-L1, p-GSK3β, CD31, and Granzyme B antibodies for immunohistochemistry (IHC).

Results:
IFNγ strongly induced PD-L1 expression in ECs. However, when ECs were exposed to OGD, IFNγ-mediated PD-L1 upregulation was compromised (from 48.9% to 31.4%). PD-L1 binding affinity of EC was also reduced after OGD (from 33.1% to 1.3%). Consistently, human (n=22) and mice (n=6) brain IHC staining found lower levels of PD-L1 and p-GSK3β in ECs and higher expression of Granzyme B in stroke samples compared to controls (p<0.05). MCAO mice treated with GSK3β inhibitor VIII showed higher PD-L1 expression and smaller infarcts.

Conclusion:
This study reveals a protective role of PD-L1 in ECs during early brain injury. Activation of GSK3β by stroke destabilized endothelial PD-L1. Thus, stabilizing PD-L1 or preventing downregulation of PD-L1 may maintain microvascular integrity and reduce neuroinflammation after stroke.
Abstract 144: Inhibition of EphrinB2 Expression in Pericytes Decreases Cerebrovascular Pathological Neovascularization in Diabetes
Authors: Abdelsaid Mohammed A , Coucha Maha , Barrett Amy C , Ergul Adviye
Published: October 2018

We have previously shown that diabetes causes dysfunctional cerebral neovascularization that increases the risk for cerebrovascular disorders such as stroke and cognitive impairment. Pericytes (PC) play a pivotal role in the angiogenic process through interaction with endothelial cells (EC). Yet, the role of PCs in dysfunctional cerebral neovascularization in diabetes is unclear. In the present study, we tested the hypothesis that the increased proangiogenic EphrinB2 signaling in PCs contributes to the dysfunctional cerebral neovascularization in diabetes.

Methods:
Type-II diabetes was induced in Wistar rats. Conditional reduction of EphrinB2 expression in rat brain PCs was achieved using stereotactic injection of AAV-virus with NG2-promoter that expresses EphrinB2 shRNA. Neovascularization was assessed using fluorescent space filling model. Novel object recognition (NOR) test was used to assess cognitive functions. Human brain microvascular PCs were grown in glucose 25 mM/palmitate 200 uM (HG/Pal) to mimic diabetic conditions. PC/EC co-culture was used to assess PC/EC interaction and angiogenic functions (scratch migration and tube formation).

Results:
Diabetes increased expression of EphrinB2 in the cerebrovasculature (2.2-Fold*) and pericytes (1.4 fold*). Diabetes significantly increased cerebral vascularization (Vascular density 3.1 fold*, tortuosity 1.07 fold* and branching density 1.5 fold*) in Wistar rats that were accompanied by deterioration of cognitive function (40% reduction*). Inhibition of EphrinB2 expression in PC significantly restored cerebral vascularization indices back to normal and improved rat cognitive functions with higher D-2 scores in NOR compared to diabetic rats*. HG/Pal increased PC/EC angiogenic properties in coculture (2-fold*). Silencing Ephrin-B2 in HBMVP significantly reduced PC migration (35 %*) and PC/EC co-culture angiogenic properties. (*p<0.05).

Conclusion:
Our findings emphasize the crucial role that PC plays in the pathological neovascularization in diabetes. EphrinB2 signaling is a promising therapeutic target to improve cerebrovascular integrity in diabetes. Yet, the molecular mechanism of the EphrinB2 signaling in PC/EC interaction is to be uncovered.
Abstract 152: Dietary Patterns Associated With Slower Cognitive Decline Post Stroke
Authors: Cherian Laurel J , Aggarwal Neelum T , Holland Thomas , Agarwal Puja , Wang Yamin , Fukuda Keiko , Morris Martha C
Published: October 2018

Introduction:
Stroke survivors are at increased risk of cognitive decline and dementia. Recent studies have shown that the MIND diet (a hybrid of the Mediterranean and Dash diets, with modifications based on the science of nutrition and the brain) slows cognitive decline in the general population, but it is not known whether the diet may also be effective in stroke survivors.

Methods:
A total of 106 participants from an observational prospective cohort study with a history of stroke at their baseline enrollment were assessed annually for an average of 4.7 years of follow-up. Participants with baseline dementia, missing or invalid baseline dietary evaluations, or less than two cognitive assessments were excluded. Cognition in five cognitive domains were assessed using structured clinical evaluations that included a battery of 19 cognitive tests. MIND diet scores were computed using a valid food frequency questionnaire. Dietary components of the MIND diet included whole grains, green leafy and other vegetables, berries, beans, nuts, lean meats, fish, poultry, and olive oil and less consumption of regular cheese, butter and sweets. MIND diet scores were modeled in tertiles. Change in global cognitive scores was regressed on baseline MIND score using linear mixed models adjusted for age and other potential confounders.

Results:
In the age adjusted model, the top tertile of MIND diet scores versus the lowest tertile was positively associated with a slower rate of global cognitive decline (β = .08; P = .02.) With further adjustment for sex, education, apo-E4, late-life cognitive activity, caloric intake, physical activity, and smoking the association remained unchanged (β = .08; P = .03).

Conclusions:
High adherence to the MIND diet was associated with substantially slower rate of cognitive decline in stroke survivors. A dietary intervention trial would be necessary to validate the role of the diet in long-term outcomes for stroke survivors.
Abstract 153: The Preserve Trial: Intensive Blood Pressure Lowering and Cerebral Blood Flow in Small Vessel Disease
Authors: Ford Gary A , Markus Hugh , Croall Iain , Moyhnihan Barry , Dixit Anand , O’Brien John , Morris Robin , Barrick Thomas , Khan Usman , Tozer Dan , Blamire Andrew
Published: October 2018

Background and Aims:
In patients with severe cerebral small vessel disease (SVD), in whom both cerebral blood flow and cerebral autoregulation are reduced, intensive BP lowering might reduce cerebral blood flow (CBF) and increase the rate of white matter hyperintensity (WMH) progression. In an RCT we determined the effect of intensive BP lowering on CBF in lacunar stroke with confluent WMH.

Method:
In the PRESERVE trial Perfusion sub-study, patients from 2 sites with MRI confirmed symptomatic lacunar infarct and confluent WMH were randomised to “normal” (systolic=130-140mmHg, N=33) versus “intensive” (systolic=<125mmHg, N=29) BP targets. CBF was determined using arterial spin labelling; the primary end point was change in global CBF between baseline and 3 months. Linear regression was performed comparing change in CBF against change in BP. Analyses controlled for site.

Results:
Mean(SD) systolic BP reduced by 8(12) and 27(17)mmHg in the standard/intensive groups, respectively (difference between groups
p
<0.001) with achieved BP of 141(13) and 126(10) mmHg respectively. Baseline global CBF was 32(10) and 31(10)ml/min/100g in the standard/intensive groups. There was no difference in change in global CBF between treatment arms: standard, mean(SD) (ml/min/100g)=
-0.46
(9.39); intensive,
0.73
(8.62),
p
=0.63. No differences were observed when analysis examined grey or white matter only, or was confined to those achieving target BP. Change in CBF did not have a significant association with change in systolic or diastolic BP.

Conclusion:
Intensive BP lowering did not reduce CBF in severe SVD characterised by lacunar stroke and confluent WMH. This suggests intensive CBF reduction is unlikely to accelerate WMH progression.
Abstract 155: What Predicts Symptomatic Intracranial Hemorrhage in Ischemic Stroke Patients Undergoing Emergent Brain Imaging for Neurological Deterioration After IV tPA?
Authors: James Brandon , Chang Andrew , McTaggart Ryan , Hemendinger Morgan , Narwal Priya , Dakay Katarina , Ricci Brittany A , MacGrory Brian , Cutting Shawna , Burton Tina , Reznik Michael , Mahta Ali , Wendell Linda , Thompson Bradford , Siket Matthew , Madsen Tracy , Khatri Pooja , Furie Karen , Jayaraman Mahesh , Yaghi Shadi
Published: October 2018

Background:
Early neurological deterioration (END) prompting urgent brain imaging occurs in up to 15% of ischemic stroke patients receiving intravenous tissue plasminogen activator (tPA). Most of these are not related to symptomatic intracranial hemorrhage (sICH) but lead to unnecessary interruption of the tPA infusion. We aim to determine predictors of sICH in ischemic stroke patients undergoing emergent brain imaging after tPA.

Methods:
We queried our prospective stroke database and included all patients who received tPA for ischemic stroke from March 1
st
, 2015 until March 1
st
, 2017. We then identified patients who underwent emergent brain imaging before the planned 24-hour brain imaging and divided these patients into: sICH+ and sICH- defined by NINDS criteria. We compared baseline clinical factors, pre-admission medications, admission blood pressure, symptoms prompting repeat scan [change in level of consciousness (LOC); worsening or new (W/N) neurological symptoms without change in LOC; headache/nausea/vomiting), thrombectomy, 24-hour NIHSS and 90 day outcome.

Results:
We identified 511 patients who received tPA (sICH rate 4.1%). Emergent repeat brain CT was performed on 108 (21.1%); 17.5% (19/108) had sICH and 21.3% (23/108) occurred during the tPA infusion with only one being related to sICH. The mean time from tPA infusion to symptoms prompting brain imaging in sICH was 7.3 ± 5.3 hours. In patients who underwent emergent brain imaging, sICH+ patients were older (80.2 ± 15.8 vs. 70.8 ± 15.4, p = 0.026), with higher admission NIHSS (14 vs. 7, p = 0.0016) and 90-day mortality (87.5% vs. 22.4%, p<0.001), more likely to have a change in LOC (78.9% vs. 21.3%, p<0.001) and less likely to have W/N symptoms without LOC change (5.3% vs. 42.7%, p=0.002). On multivariable analyses, the only predictor of sICH was LOC change (OR 6.62 95% CI 1.64-26.70, p=0.008).

Conclusion:
Nearly 95% of patients with ischemic stroke had unnecessary interruption of the tPA infusion for new symptoms shortly after the tPA infusion. A change in LOC was the only predictor of sICH among tPA patients undergoing emergent brain imaging. In this group of patients, the preparation of tPA reversal agents awaiting brain imaging may help reduce tPA reversal times and improve outcomes
Abstract 16: Oligodendrocytes Provide Trophic Support to Vasculature Following Ischemic Stroke in Neonatal Mice
Authors: Schroeder Christian , Verden Dylan , Hashimoto Hirokazu , Traystman Richard J , Macklin Wendy B , Herson Paco S
Published: October 2018

Introduction:
Incidence of perinatal arterial ischemic stroke (PAIS) is surprisingly high, approaching that of the elderly. It has been postulated that the developing brain has a greater degree of plasticity and capacity for repair compared to the adult, thereby enhancing functional recovery. To address this issue, we utilized the recently developed intraluminal filament mouse model of ischemic stroke in postnatal day 10 mice. The aim of this study was to examine the cellular responses to ischemic stroke in the neonatal brain that contribute to the enhanced functional recovery.

Method:
Middle cerebral artery occlusion (45 minutes) was performed on adult and p10 mice using the intraluminal filament method. Immunohistochemistry was performed to identify oligodendrocyte precursors (PDGFRα/Olig2+), mature oligodendrocytes (CC1/Olig2+), vascular endothelial cells (Glut-1) and pericytes (CD13), and TUNEL to identify injured cells. Blood brain barrier integrity was examined by staining for fibrinogen. A protein array was conducted to examine extracellular protein levels. In situ hybridization was used to confirm source of IGF-1.

Results:
Oligodendrocytes were remarkably resistant to ischemic insult in the neonatal brain up to 7 days after injury; no change in oligodendrocyte precursor or mature oligodendrocyte cell count following neonatal stroke, compared to the significant loss of oligodendrocytes following adult stroke. In contrast, large numbers of TUNEL+ neurons were observed in both groups following stroke. In contrast to well-established vascular injury in adult stroke, no change in vascular integrity (Glut-1 positive vessel length/number or fibrinogen leakage) was detected following neonatal stroke. Unbiased analysis of extracellular protein levels in the adult and neonatal brain following stroke identified IGF-1 as a protein uniquely up-regulated following neonatal stroke. In situ hybridization revealed increased IGF-1 mRNA levels in oligodendrocytes following neonatal stroke.

Conclusion:
These results suggest that ischemia-resistant developing oligodendrocytes provide trophic support (IGF-1) to the vasculature following neonatal stroke.
Abstract 160: Outcomes and Relationship to Time: Alteplase Administration in Patients With Large Vessel Occlusion in Non-intervention Group of the Hermes Collaboration
Authors: Goyal Mayank , Almekhlafi Mohammed , Dippel Diederik W , Campbell Bruce , Muir Keith , Demchuk Andrew , Bracard Serge , Davalos Antoni , Guillemin Francis , Jovin Tudor , Menon Bijoy K , Mitchell Peter , Brown Scott B , White Phil , Majoie Charles , Saver Jeffrey L , Hill Michael D
Published: October 2018

Background:
Data on outcomes and time effects of intravenous alteplase on outcome of patients with documented large vessel occlusion (LVO) are scarce.

Aim:
To define the effect of onset to treatment time (OTT) on functional outcomes and mortality among patients in the non-interventional arm of endovascular stroke trials.

Methods:
Individual patient-level data from the HERMES collaboration were pooled from seven trials that randomized patients with proven LVO to mechanical thrombectomy + best medical therapy vs. best medical therapy alone. In this analysis only patients who received alteplase directly at the endovascular hospital were included. Primary outcome was degree of disability (mRS distribution) at 3 months. Secondary outcomes included functional independence (mRS 0-2) at 3 months, mortality by 3 months, and symptomatic intracranial hemorrhage (sICH).

Results:
Among 893 patients in the control arms, 601 received alteplase at the endovascular hospital. The mean age was 66.0 years (SD 13.9), 50% were women, and median NIHSS was 17. 82% were treated within 3 hours from onset and 17% between 3 and 4.5 hours. SICH was observed in 20/585 (3.4%), 3.5% with OTT within 3h vs 3.2% with OTT 3-4.5 hours, p = 1.00. For each 60-minute delay in therapy the cOR for improvement on the mRS was 0.80 (95% CI 0.68 to 0.95, p=0.01) (Figure-A). For each 60-minute delay, the OR for functional independence (mRS 0-2) was 0.82 (95%CI, 0.66 to 1.03, Figure-B). There was no time effect on mortality (cOR, 0.99 (95%CI, 0.79 to 1.23). The reduction in treatment effect by time was not modified by age, baseline NIHSS score, baseline ASPECTS score or occlusion location (p
interaction
=0.21, 0.81, 0.88, 0.67 respectively).

Conclusion:
Faster intravenous thrombolysis delivery is associated with better functional recovery in patients with LVO not destined to receive mechanical thrombectomy.
Figure legend:
A: 90-day functional outcomes stratified by OTT. B: Proportion of mRS 0-2 the 90-day against OTT
Abstract 168: Interim Analysis of the SMART Registry on the Utility of the Penumbra Smart Coil System in Treatment of Intracranial Aneurysms and Malformations
Authors: Spiotta Alejandro , Liu Kenneth , Schirmer Clemens , Bellon Richard , Bohnstedt Bradley , Fiorella David
Published: October 2018

Introduction:
Smart Coils are novel generation embolic coils designed with robust shape and multiple transitions of softness to promote dense packing and durable long term occlusion. We report data on the utility of the Penumbra Smart Coil System in treatment of a variety of intracranial vascular lesions such as aneurysms and other abnormalities.

Methods:
SMART is a prospective, multicenter registry on the benefits of Smart Coils for treatment of cerebral aneurysms and malformations. This interim analysis aims to evaluate data from the initial 250 patients. Procedures must employ ≥75% of the Smart, PC400, or POD coils to meet the registry criteria. Study endpoints include procedural device-related serious adverse events (SAE), and the occlusion status immediately post procedure. Follow-up will be conducted through 1 year.

Results:
A wide range of presenting lesions were observed in the first 250 consecutive patients enrolled, including aneurysms (87.9%), of which 27.6% were ruptured, arteriovenous malformations (1.2%), fistulae (6.1%), and other (4.9%). At presentation, 67.9% were female, and the mean age was 58.9 ± 14.6 years. Aneurysms were small (<11mm, 89.8%), large (11-25mm, 9.7%), and giant (>25mm, 9.7%), with 62.6% having a wide neck (≥4mm). Procedural metrics and outcome can be found in Table I; coil deployment time is defined as the time from the first coil deployed until the last coil detachment. For all patients, adequate occlusion as adjudicated by the investigator was achieved for 98.4% (242/246). In aneurysm patients, where known, class I & II Raymond Roy Occlusion was 82.7% (177/214). Procedural device-related SAE were observed in 7 subjects (2.8%). Mortality <24h of intervention was reported in 0.8% patients, and >24h in 2.8% patients; none were device-related. One-year follow-up data is ongoing.

Conclusion:
Initial results suggest that Smart Coil achieves adequate embolization in a variety of neurovascular lesions.
Abstract 174: Preeclampsia and Early Stroke Incidence in the California Teachers Study
Authors: Miller Eliza C , Boehme Amelia K , Park Moon Yeseon , Cheung Ying Kuen K , Chung Nadia T , Wang Sophia S , Lacey James V , Willey Joshua Z
Published: October 2018

Background:
Preeclampsia (PEC) occurs in 3-8% of all pregnancies and doubles women’s long-term stroke risk. Prospective data are limited regarding the rate at which this risk develops. We hypothesized that history of PEC would increase risk of early stroke (ES), defined as stroke before age 60 without concurrent PEC, in women in the California Teachers Study (CTS), and that the risk would be modified by aspirin or statin use.

Methods:
CTS participants aged ≤60 years with no prior stroke at time of enrollment in 1995 were included in this analysis. Baseline characteristics and medical and gynecological history were obtained by serial questionnaires. Participants were followed prospectively and stroke outcomes obtained via linkage with California hospital records through 12/31/2012. Poisson regression was used to calculate relative risk of ES incidence, among those with and without history of PEC, in unadjusted and adjusted models. We used stratified analyses to assess risk of ES in women with and without self-reported use of aspirin and/or statins.

Results:
Of the 60,817 women included in the analysis, 3734 (6.1%) had PEC. Incident ES occurred in 49 (1.3%) women in the PEC group and 430 (0.8%) in the non-PEC group. Risk of ES incidence was greater in women with PEC compared to non-PEC in unadjusted models (RR 1.7, 95%CI 1.3-2.3). Adjusting for age, hypertension, diabetes, migraine, and obesity, RR remained higher in the PEC group (RR 1.4, 95%CI 1.1-1.9). Stratified analyses showed that this risk was mitigated in women taking aspirin or statins (RR 1.3, 95%CI 0.8-2.1), but elevated in those not taking them (RR 1.5, 95%CI 1.02-2.3).

Conclusion:
Women with prior PEC were 40% more likely than those without PEC to develop ES, even controlling for other risk factors. Women with a history of PEC should be considered high risk for ES. Randomized trials are needed to assess whether long-term use of aspirin and/or statins would benefit all women with a history of PEC.
Abstract 185: Social Network Structure and Function is Associated With Blood Pressure Reduction in Stroke Survivors
Authors: Roberts Eric T , Goldmann Emily , Boden-Albala Bernadette
Published: October 2018

Although family and friends typically provide informal care after a stroke, little is known about the relationship between social network structure and function and post stroke outcomes. As part of the Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) trial, stroke/TIA patients were asked to identify up to 5 persons (“alters”) with whom they discuss important matters and provide information about each relationship. Network characteristics included number of alters, having an alter in the same household, having a family-only (vs. family and friend) network, frequency of contact with each alter, likelihood of discussing health concerns, relationship “closeness,” and educational level of each alter. Our outcome was the difference in systolic blood pressure (BP) between baseline and the 12 month follow-up (mmHg). We regressed BP change on our social network variables adjusting for trial arm, age, gender, race-ethnicity, and education. Of the 478 participants, 14% identified no alters, 58% identified 1 or 2 alters, and 28% identified 3-5 alters. Of those with at least one alter, 61% reported having an alter in the same household and 73% reported having a family-only network. Twenty-one percent of respondents reported talking to at least 3 alters at least several days per week, 22% reported having at least 3 alters whom they were very likely to discuss health concerns with, 23% reported having extremely or very close relationships with at least 3 alters, 14% of respondents reported having 3 or more alters with more than a high school education. In fully adjusted models, having 3-5 alters compared to none (beta = 10.86; p = 0.01), not having a family only network (beta = 6.11; p = 0.03), having at least 3 health matters network members compared to none (beta = 9.81; p = 0.01), having at least 3 extremely or very close relationships compared to none (beta = 9.18; p = 0.02), and having 3-5 network members with more than a high school education (beta = 11.77; p < 0.01) or 1-2 network members with more than a HS education (beta = 7.04; p = 0.04) compared to none was associated with greater mean BP reduction. Interventions that involve social networks may help reduce vascular risk and enhance secondary prevention efforts.