bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP394: Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial
Authors: Johnston S. Claiborne , Easton J. Donald , Kim Anthony J. , Farrant Mary , Elm Jordan , Palesch Yuko , Barsan William , Lindblad Anne , Conwit Robin
Published: October 2018

The
P
latelet-
O
riented
I
nhibition in
N
ew
T
IA and minor ischemic stroke (POINT) Trial is a prospective, randomized, double-blind, multicenter international trial with the primary null hypothesis that in patients with TIA or minor ischemic stroke treated with aspirin 50-325 mg/day, there is no difference in survival free of ischemic stroke, myocardial infarction, and ischemic vascular death at 90 days in those treated with clopidogrel (600 mg loading dose then 75 mg/day) compared to placebo when therapy is initiated within 12 hours of time last known free of new ischemic symptoms.

Methods:
The primary endpoint is a composite outcome of new ischemic events: ischemic stroke, myocardial infarction or ischemic vascular death. Subjects are 18 years or older with high-risk TIA (ABCD
2
score ≥ 4) or minor ischemic stroke (NIHSS ≤ 3) meeting eligibility criteria who can be randomized within 12 hours of the qualifying event. Follow-up is 90 days from randomization so event rates are high throughout the period of study. A total of 5,840 patients will be recruited. The first subject was enrolled on May 28, 2010; international sites joined in August 2013.

Principal Investigator:
S. Claiborne Johnston, MD, PhD, The University of Texas at Austin

Co-Principal Investigators:
J. Donald Easton, MD, University of California, San Francisco; Anthony S. Kim, MD, MAS, University of California, San Francisco

Contact:
Mary Farrant, MBA, BSN, RN, University of California, San Francisco, Director, POINT Trial —UCSF Clinical Coordinating Center (CCC), San Francisco, California, 94158; Phone: 1-415-502-7304; Email:
mary.farrant2@ucsf.edu

Planned Number of Centers:
225; Present Number: 195

Planned Number of Subjects:
5,840; Present Number: 4,586 (June 2017)

Sponsor:
University of California, San Francisco (UCSF); National Institute of Neurological Disorders and Stroke (NINDS)

Collaborators:
Neurological Emergencies Treatment Trials Network (NETT); Statistics and Data Management Center (SDMC) at Medical University of South Carolina (MUSC); POINT Clinical Research Collaboration (POINT-CRC) at EMMES Corporation

Dates of Study:
October 2009 - April 2021

ClinicalTrials.gov Identifier:
NCT00991029
http://clinicaltrials.gov/ct2/show/NCT00991029?term=POINT&rank=1
Abstract WP399: Change in Antiplatelet Therapy in Prevention of Secondary Stroke (CAPS2) Study
Authors: Lim Mihyun , Redd Kolby , Giamberardino Lauren , Duda Viktoriya , Mehta Sonal , Yallapragada Anil , Kothari Ravish , Powers William J , Sen Souvik
Published: October 2018

Introduction and Hypothesis:
Approximately a third of stroke/TIA events occur in patients taking daily Aspirin. We studied the comparative effectiveness of FDA approved antiplatelet agents (Aspirin, Clopidogrel, and Aspirin-dipyridamole or ASA+DP) in prevention of recurrent vascular events in stroke/TIA patients on Aspirin.

Methods:
Consecutive patients identified as having stroke or TIA were screened and enrolled into this prospective longitudinal registry. Patients on dual antiplatelet therapy or oral anticoagulants were excluded. Patient’s etiological stroke subtype, medication history, medication compliance and Aspirin Platelet Function Test were assessed at baseline. Changes in antiplatelet regimen including Aspirin dose, Clopidogrel, ASA+DP, changes in statin therapy were recorded. Follow up 6 and 12 month phone visits were conducted to assess primary outcomes (stroke/TIA, MI, death), adjudicated by chart review.

Results:
A total of 183 subjects (mean age 68+12, 58% males, 50% white, 44% African-American) were enrolled over a 24 month period on Aspirin. Majority (63%) had ischemic stroke (NIHSS: 0-21) and remaining (37%) had TIA (ABCD
2
: 2-7). Ischemic strokes were attributed to penetrating artery disease (41%), large artery atherosclerosis (35%), other/undetermined (18%), and cardiogenic (6%). After 12-months, 4.9% of participants on Clopidogrel, 15.1% of participants on aspirin and 35.3% of participants on ASA+DP had a primary outcome (p=0.006), depicted in the Kaplan-Meier curve. Changes in Aspirin dose from 81mg to 325mg or statin therapy regimen did not appear to impact primary outcome.

Conclusions:
This study shows a significant difference in secondary vascular event within 12 months of stroke/TIA on Aspirin, with effectiveness recorded in the order: Clopidogrel>Aspirin>ASA+DP. A larger randomized pragmatic trial may help ascertain this finding and clarify if specific subtype benefit from specific antiplatelet agent.

Figure:
Abstract WP403: Patent Foramen Oval (PFO) Shunting is Associated With White Matter Hyperintensity (WMH) in Stroke Patients
Authors: Deng Wenjun , Song Bo , Fisher Lindsay , Chou Richard I , Oyer Maxwell , Bunda Bridget , Wang Andrew , McMullin David , Buonanno Ferdinando S , Lo Eng H , Ning MingMing
Published: October 2018

Background:
Clinical trials report PFO closure to decrease the long-term risk of recurrent paradoxical stroke. We previously found that PFO is not just a back door to clotting, but may increase the risk of chronic neurovascular injury via venous arterial mixing resulting in elevated oxidative mediators. In this study, we prospectively explore the relationship of PFO shunting and chronic WMH, a surrogate for chronic neurovascular injury, compared to non-PFO-related cryptogenic stroke (CS).

Method:
PFO and non-PFO CS patients were consecutively recruited in accordance with IRB (n=81 PFO; n=98 non-PFO CS). WMHs were scored by vascular neurologist blinded to patient outcome.

Result:
Compared to CS without PFO, PFO pts had increased WMH burden as measured by Scheltens scale. WMH burden was independently associated with PFO after adjusting for age, gender, NIHSS and disease status (odds ratio: 1.19, p = 0.003). Moreover, in pts s/p PFO closure, WMH score was significantly higher in those with residual shunting as compared with complete closure (Figure 1, 1 vs 8.25, p = 0.038).

Conclusion:
Our results suggest an important association between PFO-related blood shunting and chronic neurovascular injury as measured by cerebral WMH. Studies in a larger patient cohort are ongoing to investigate the mechanistic relationship between PFO shunting and WMH.
Abstract WP407: Function and Reactivity of Pial Collaterals In Vivo in Normotensive and Hypertensive Rats: Response to Ischemia and Reperfusion
Authors: Chan Siu-Lung , Liebeskind David S , Ayata Cenk , Cipolla Marilyn J
Published: October 2018

Background:
Collateral therapeutics is an emerging treatment for acute ischemic stroke. However, whether pial collaterals have tone in vivo and thus the ability to vasodilate is not clear. We investigated the function of pial collaterals in vivo during ischemia and reperfusion in normotensive and hypertensive rats that are known to have poor collaterals. We hypothesized that pial collaterals from spontaneously hypertensive rats (SHR) would have greater basal tone during ischemia and reperfusion than normotensive Wistar rats that could contribute to decreased collateral perfusion.

Methods:
A cranial window was performed in SHR (n=4) and Wistar (n=4) rats prior to remote middle cerebral artery occlusion (MCAo) under pentobarbital anesthesia. Video microscopy was used to measure changes in diameter of leptomeningeal anastomoses (LMAs) during MCAo for 2 hrs and 2 hrs reperfusion (Figure, top). After reperfusion, the brain surface was exposed to physiological saline solution with EDTA (67 mmol/L) to measure fully relaxed diameters and calculate basal tone. Blood pressure was measured via arterial catheter and animals were mechanically ventilated to control blood gases.

Results:
Blood pressure was significantly elevated in SHR vs. Wistar rats (157±9 vs. 107±7; p<0.01). LMAs (~15-20 μm diameters) had basal tone that was higher in SHR vs. Wistar (15.4±9% vs. 8.4±4.9%; n.s.). After 5 min MCAo, tone in LMAs from Wistar rats decreased to 2.7±1.5% but increased to 17.2±9.7% in SHR. Reperfusion caused vasoconstriction of LMAs from both groups and increased tone to 18.7±5.3% in Wistar and to 29.5±9.7% in SHR (p<0.01 vs. basal for both; Figure, bottom).

Conclusions:
These data demonstrate functional pial collaterals in normotensive and hypertensive rats. While increased tone of LMAs during MCAo in SHR could limit perfusion to the penumbra, vasoconstriction of LMAs from both groups suggests therapeutic intervention to increase diameter and salvage at risk tissue is possible.
Abstract WP410: Reduced Recovery of Penetrating Arteriole Flow and Increased Capillary Transit Time Heterogeneity After Stroke in Type 2 Diabetic Mice
Authors: Kanoke Atsushi , Li Yuandong , Song Shaozhen , Wang Ruikang K , Liu Jialing
Published: October 2018

Introduction:
Capillary transit time heterogeneity (CTTH) is altered during functional activation and in pathological conditions, affecting the extraction efficiency of oxygen from blood. Diabetes deteriorates ischemic brain damage, although the impact of diabetes in microvascular environment remains insufficiently characterized. Cerebral microvascular blood flow is considered to be regulated by pericytes, which are reportedly less in the retina of diabetic patients. However, it still remains unclear whether type 2 diabetes (T2DM) specifically affects hemodynamic adaptation of microvessels during cerebral ischemia.

Hypothesis:
MTT and CTTH are increased after ischemic stroke and exacerbated by T2DM, which is associated with a greater hemodynamic compromise.

Methods:
A 4x4 mm
2
cranial window was created on the parietal cortex 2 mm lateral and 1 mm posterior from the bregma three weeks prior to imaging. Experimental stroke was induced by permanent distal middle cerebral artery occlusion (dMCAO) combined with 90 minutes-occlusion of the ipsilateral common carotid artery. Spatial and temporal changes of the total flow and axial velocity of the penetrating arterioles (PA), as well as mean transit time (MTT) and CTTH in the capillaries bordering the distal MCA and ACA branches were determined by optical coherent tomography-based microangiography and capillary velocimetry at baseline, during dMCAO, 1hr and 24 hrs after reperfusion in
db/+
and
db/db
mice, a mouse model of obesity and T2DM.

Results:
Stroke-induced increase in MTT and CTTH was greater in the
db/db
compared to
db/+
mice, leading to increased microvascular resistance and reduced oxygen extraction after stroke in the former. The total blood flow in PA reduced immediately after dMCAO in both strains of mice by nearly 80%, but it remained reduced in the db/db mice after reperfusion in contrast to a sustainable recovery at 50% of prestroke level.

Conclusions:
T2DM is an additional risk factor for hemodynamic compromise during cerebral ischemia, which may increase the severity of stroke. The mechanisms underlying T2DM exacerbated CTTH and reduced recovery of PA flow are under investigation.
Abstract WP418: Mineralocorticoid Receptor Signaling is Associated With Neuroinflammation and Changes in Cognitive Function in Angiotensin II-Induced Hypertension
Authors: Diaz-Otero Janice M , Yen Ting-Chieh , Bota Daniel , Dorrance Anne M
Published: October 2018

Introduction:
Mineralocorticoid receptor (MR) activation facilitates hypertension-associated cerebral artery dysfunction and reduced perfusion that may increase the risk for vascular dementia.

Hypothesis:
Angiotensin II (AngII)-hypertension results in neuroinflammation and oxidative stress that will impair cognition in a MR-dependent manner.

Methods:
16-17 week old male C57bl/6 mice were treated with AngII (800ng/kg/min) ± the MR antagonist, eplerenone (EPL;100mg/kg/day) for 4 weeks; Sham mice served as control. Data are presented as mean ± SEM; n=4-12 per group *=different from Sham.

Results:
AngII reduced astrocyte density and increased microglial density; the changes in microglia were prevented by EPL. AngII reduced the mRNA expression of brain-derived neurotrophic factor (BDNF), doublecortin, glial fibrillary acidic protein (GFAP), and synaptophysin (SYP); the reductions in BDNF, GFAP and SYP mRNA expression were prevented by EPL. We assessed cognitive function using the Barnes maze; AngII treated mice spent less time in the target quadrant than the sham or AngII+EPL mice. There was a trend toward there being an increase in the latency to reach the target quadrant in the AngII mice but the changes were not significant. Changes in nest building are associated with cognitive decline, nest building was impaired in AngII mice and these changes were prevented by EPL. There was a trend for oxidized proteins to be increased in AngII mice that may be prevented by EPL but these changes were not significant. Preliminary studies suggest that AngII changes the morphology of cortical neurons suggesting that the increased blood pressure may lead to unhealthy neurons.

Conclusion:
AngII-hypertension results in neuroinflammation and creates an environment where markers for neuronal support and synapse formation are impaired. These changes are regulated by MR signaling and may be associated with the declined cognitive function.
Abstract WP424: Average Time From Ct to Ctp Completion is Long: What Are We Getting in Return?
Authors: Hassan Ameer E , Shariff Umar , Sanchez Christina , Malik Ahmed , Qureshi Adnan
Published: October 2018

Background and Purpose:
Studies have shown that CT perfusion (CTP) guided endovascular treatment (EVT) increases the rate of favorable outcome in patients with acute ischemic stroke (AIS). The aim of our study is to determine whether we are wasting too much time between noncontrast CT (NCT) imaging completion and CTP completion and the effect it has on clinical outcomes.

Methods:
We utilized our endovascular database and analyzed EVT patients. We compared the average time from door to NCT completion with the average time to CTP completion using a paired t-test. Baseline demographics, clinical characteristics, NIH Stroke Scale on admission and discharge, modified Rankin Scale (mRS) at discharge, and presence of intracranial hemorrhage were collected. A linear regression model was created to determine the effect of door time to NCT only completion and time to CTP completion on outcomes.

Results:
288 patients (mean age 71.4 ± 12.8 years; 56.6% females) underwent EVT. 220 patients had EVT after both NCT and CTP and 68 patients underwent treatment right after NCT. There was no difference in baseline demographics and clinical characteristics. (Table 1) The mean completion time for NCT only was 20.0 ±2.8 minutes vs. 75.8 ±152.3 minutes for NCT and CTP (p <.0001). Ninety-day mortality was similar in patients with both NCT and CTP and in patients with only NCT (18.2% versus 20.6%; p=.84). Comparing the CTP patients with the NCT only patients, favorable discharge outcome (mRS 0-2) was observed in 24.1% versus 25.0%, respectively (p=.87). In hospital mortality was observed in 18.6% of CTP and 23.5% of NCT only patients (p=.39).

Conclusions:
Our study shows that patients with AIS undergoing EVT take significantly more time for CTP completion with no improvement in outcomes compared to NCT only selected patients. Large prospective studies are further warranted to study CTP use in EVT and to establish and validate the usage of CTP before widespread implementation.
Abstract WP48: Computed Tomography Perfusion Core Infarct Measurement Compared to Diffusion-Weighted Magnetic Resonance Imaging in Patients With Revascularization of Anterior Circulation, Large Artery Occlusions
Authors: Karamchandani Rahul R , Singh Sam J , Rhoten Jeremy B , Strong Edwin D , Raheem Enayetur , Bodle Jeffery D , Hines Andrew U , Asimos Andrew W
Published: October 2018

Introduction:
Automated CT Perfusion (CTP) technology offers the potential to distinguish irreversibly damaged tissue from “at-risk,” potentially salvageable tissue. Regional Cerebral Blood Flow (CBF) < 30% has been identified as a good predictor of infarct core on CTP. Randomized trials investigating mechanical thrombectomy for large artery occlusion (LAO) acute ischemic stroke (AIS) have excluded patients with large core infarcts. We investigated the relationship between infarct core, as predicted by CTP, compared to the gold standard of DWI MRI, after revascularization of a proximal, anterior circulation, LAO AIS.

Hypothesis:
CBF < 30% overestimates core infarct size compared to DWI MRI in at least one-third of patients with occlusions of the internal carotid artery (ICA) or middle cerebral artery (MCA) M1 or M2 segments treated with endovascular therapy achieving thrombolysis in cerebral infarction (TICI) grade 2b or 3.

Methods:
From a large healthcare system’s stroke network database, we conducted a retrospective analysis comparing infarct core (CBF < 30%; RAPID iSchemaView) and post-revascularization DWI MRI (ADC < 620cc; RAPID iSchemaView) in patients with ICA, M1, or M2 LAO AIS between November 2016 and June 2017 with TICI 2b or 3 reperfusion.

Results:
Over an 8-month period, 25 cases were identified with pre-treatment CTP, post-intervention MRI, and TICI 2b/3 revascularization of an ICA, M1, or M2 occlusion. Mean age was 61.1 years old and median NIHSS was 16. Mean duration from last known well time to CTP and MRI was 4.2 and 27.1 hours, respectively. Sixteen patients were treated with IV TPA and endovascular intervention, while 9 underwent only endovascular intervention. Median time to revascularization was 5.6 hours. CTP overestimated infarct size compared to follow-up MRI in 9/25 (36%) cases by an average of 17.8cc. Pearson correlation coefficient between CTP core infarct size and MRI infarct size was non-significant (r = 0.17, p = 0.41).

Conclusions:
Core infarct size may be overestimated by CTP in a substantial number of patients with revascularization of proximal, anterior circulation LAO AIS. Caution should be exercised when using core infarct estimation of CBF < 30% to exclude patients from endovascular therapy.
Abstract WP5: Reperfusion Reduces Brain Edema in Patients With Acute Ischemic Stroke. A MR CLEAN Substudy
Authors: Kimberly W. Taylor , Dutra Bruna G , Boers Anna M , Alves Heitor C , Berkhemer Olvert A , van den Berg Lucie , Sheth Kevin N , Roos Yvo B , van der Lugt Aad , Beenen Ludo F , Dippel Diederik W , van Zwam Wim H , van Oostenbrugge Robert J , Lingsma Hester F , Marquering Henk , Majoie Charles B ,   on behalf of the MR CLEAN investigators
Published: October 2018

Introduction:
The main objective of this study was to elucidate the relation between reperfusion and brain edema. The secondary objective was to evaluate if brain edema partially mediated worse outcome in patients without reperfusion, or in patients with delayed reperfusion or a lower ASPECTS.

Methods:
MR CLEAN was a prospective, randomized, multicenter clinical trial of endovascular treatment (EVT) compared to conventional care. In this exploratory post hoc study, 462 of 500 patients were included. Brain edema was assessed by midline shift (MLS) measured on follow-up CT scans. Reperfusion status was assessed by the modified thrombolysis in cerebral infarction (mTICI) score in the EVT arm. The modified Arterial Occlusive Lesion (mAOL) score was used to evaluate the recanalization status in both arms. The associations between MLS and modified Rankin Scale (mRS), and MLS with reperfusion or recanalization were performed in univariable and multivariable analyses. Mediation analyses were performed to determine whether MLS was partially responsible for worse functional outcome in the groups without reperfusion or recanalization, and in the groups with delayed reperfusion or lower ASPECTS.

Results:
Reperfusion and recanalization were associated with reduced likelihood of having MLS (acOR 0.26, 95%CI 0.13-0.51, p < 0.001; acOR 0.38, 95%CI 0.24-0.60, p < 0.001 respectively). Accordingly, the presence of MLS was associated with an increased risk of worse 90-day outcome (acOR 3.89, CI 2.71-5.61, p < 0.001). In mediation analysis, MLS was partially responsible for worse mRS scores in patients without reperfusion or recanalization, and in those with delayed reperfusion or lower ASPECTS (MLS changed the logistic regression coefficients by 30.3%, 12.6%, 33.3%, and 64.2%, respectively).

Conclusion:
Successful reperfusion or recanalization reduces brain edema, reflected by MLS. The presence of MLS mediated part of the worse functional outcomes in patients without reperfusion or in those patients with delayed reperfusion or a lower ASPECTS. This study confirms a pleiotropic benefit of reperfusion that extends beyond the concept of rescuing ischemic brain tissue at risk for infarction.
Abstract WP50: Potential Impact of Triage Using Non-Contrast Head CT and Stroke Severity on a Regional Stroke System of Care: A Population-Based Study
Authors: Kircher Charles E , Kleindorfer Dawn , Moomaw Charles , Alwell Kathleen , Sucharew Heidi , Woo Daniel , Flaherty Matthew L , Martini Sharyl , Mackey Jason , De Los Rios La Rosa Felipe , Ferioli Simona , Kissela Brett M , Adeoye Opeolu
Published: October 2018

Background and Purpose:
Acute ischemic stroke (AIS) patients may benefit from endovascular therapy (EVT) up to 24 hours since last known normal (LKN). Advanced imaging, including CT or MR angiography and perfusion studies, is required for patient selection. Large non-thrombectomy centers may be able to obtain and interpret these images quickly, but smaller hospitals may not have sufficient real-time CT technician and radiology support. We estimated transfer rates using non-contrast head CT and stroke severity to select patients to be transferred to larger centers for evaluation.

Methods:
We identified all AIS among residents of the Greater Cincinnati/Northern Kentucky Stroke Study region in 2010 comprising approximately 1.3 million people. Study nurses abstracted relevant information from the medical record, including times of symptom onset, LKN, and ED arrival, and all cases were verified by study physicians. Only cases age ≥18 with baseline mRS 0-2 that presented to an ED were included. Among cases that presented between 6 and 24 hours from LKN, those without evidence of acute infarct on head CT and with initial NIHSS ≥6 or ≥10 were identified.

Results:
Of 1359 AIS cases at local EDs, 448 (33.0%) presented between 6 and 24 hours, of which s383 (85.5%) showed no evidence of acute infarct on CT. Of cases with no acute infarct on CT, 89/383 (23.2%) had NIHSS ≥6, of which 66 (74.2%) initially presented to a hospital without thrombectomy capabilities; and 51/383 (13.3%) had NIHSS ≥10, of which 40 (78.4%) presented to a non-thrombectomy hospital.

Conclusions:
From 6 to 24 hours after stroke onset within our population, 40-66 AIS patients annually (0.8-1.3/week, or 3-5 patients per 100,000 persons per year) may present to non-thrombectomy hospitals and need to be transferred using non-contrast CT and stroke severity as screening tools. Such an approach may sufficiently mitigate the impact of delays in treatment on outcomes, without overburdening the referring nor accepting hospitals.
Abstract WP60: Kernel Spectral Regression and Neural Networks Enable Regional Detection of Hemorrhagic Transformation on Multi-Modal MRI for Acute Ischemic Stroke
Authors: Ma Samantha J , Yu Songlin , Liebeskind David S , Yan Lirong , Wang Danny J , Scalzo Fabien
Published: October 2018

Purpose:
Hyperperfusion detected on arterial spin labeling (ASL) cerebral blood flow (CBF) images acquired after acute ischemic stroke (AIS) onset has been shown to be significantly associated with development of intracerebral hemorrhage. ASL data is often too noisy for accurate voxel-based analysis alone. The purpose of this study was to develop a machine learning model for the voxel-based detection of tissue at risk for hemorrhagic transformation (HT) utilizing multiple MRI modalities.

Materials and Methods:
The present study utilized clinical MRI and ASL image data acquired from 67 AIS patients shortly after endovascular therapy. A novel regional cuboid sampling framework was developed for machine learning training, in which local cuboids were extracted from the CBF map, DWI, FLAIR, and TSE images before being matched with GRE-based manually drawn bleed groundtruth delineations. Kernel spectral regression (KSR) uses the eigenvectors of the graph representation to reveal low dimensional structure in high dimensional data. A two-layer feed-forward neural network was then built with 10 neurons in the sigmoid hidden layer and trained with scaled conjugate gradient backpropagation to classify cuboid inputs into likelihood of HT.

Results:
The proposed multimodal regional framework reached an accuracy of 80.59 ± 3% in detecting hemorrhage with KSR on our dataset (better than a voxel-based prediction on CBF with 72.80 ± 5% accuracy). Using the neural network training, the framework reached an improved accuracy of 95.1% ± 0.6%. Figure 1 shows how the regions with high likelihood of hemorrhage match well with the manually drawn regions in the reference GRE map.

Conclusion:
Kernel spectral regression and neural networks can provide more accurate detection of tissues at risk for HT. Although CBF can inform AIS patient clinical outcome, the addition of multi-modal MRI data into the regional cuboid framework substantially improves the voxel-based HT detection accuracy.
Abstract WP62: Favorable Clot Characteristics Predict Smaller Infarct Volume in Acute Ischemic Stroke Patients Treated With Reperfusion Therapy
Authors: Al Sultan Abdulaziz S , Al-Ajlan Fahad S , Najm Mohammed , Casault Colin , Neweduk Anneliese , Horn MacKenzie , Field Thalia S , Puig Josep , Castellanos Mar , Dowlatshahi Dar , Sohn Sung-II , Ahn Seong H , Poppe Alex , Mikulik Robert , Asdaghi Negar , Boulanger Jean-Martin , Asil Talip , Calleja Ana I , Goyal Mayank , Hill Michael D , Demchuk Andrew M , Menon Bijoy K
Published: October 2018

Introduction:
Multiple studies have correlated larger final infarct volume (FIV) with worse clinical outcomes. In
INTERRSeCT
, an international multicenter prospective cohort study, we sought to determine the favorable intracranial clot characteristics predicting smaller infarct volumes.

Methods:
FIV was measured (24 ±12 hours after baseline imaging) in 605 patients from
INTERRSeCT
study by blinded readers using Quantomo (Cybertrial Inc, Calgary). Clot Burden Score (CBS) is a 10-point scale with 10 referring to a completely patent ipsilateral anterior circulation from ICA to both M2 arteries, whereas 0 refers to a completely occluded ipsilateral anterior circulation. Residual Flow Grade (RFG) assesses the radiological permeability of the clot to contrast, with grade 0, 1, and 2 defined as no contrast, diffuse ghosting, and hairline lumen, respectively. Both of these scores were assessed by a blinded reader to the FIV. Using ordinal logistic regression, FIV was divided into deciles as the outcome. CBS and RFG were analyzed from 0 to 10, and 0 to 2, respectively. Two models were used, the first has no recanalization status, while the second included it.

Results:
The median FIVs with and without recanalization were 12.34 ml (IQR: 32.3 ml) and 22.15 ml (IQR: 60.12ml), respectively. CBS and RFG were independently predictive of FIV (p-value= <0.001 and 0.003, respectively). The common ORs for having one decile higher FIV for 1 point increase in CBS and RFG were 0.82 (CI: 0.77, 0.87) and 0.66 (CI: 0.51, 0.86), respectively. After adjusting for recanalization, the common ORs for having one decile higher FIV for 1 point increase in CBS and RFG were 0.83 (CI: 0.78, 0.88) and 0.72 (CI: 0.54, 0.94), respectively.

Conclusions:
Residual flow grade and clot burden score are fast and practical techniques for practitioners treating acute ischemic stroke patients. Favorable RFG and CBS independently, predict lower infarct volumes regardless of whether recanalization achieved.
Abstract WP65: Higher Glucose Level Associated With Unfavorable Outcome in Acute Minor Ischemic Stroke After Thrombolytic Therapy
Authors: Jiang Fang , Zhang Qian , Zhao Wenbo , Che Ruiwen , Huang Xiaoqin , Dong Kai , Ma Qingfeng , Song Haiqing , Ding Jianping , Feng Wuwei , Ovbiagele Bruce , Ji Xunming
Published: October 2018

Introduction:
In real world practice, patients with minor stroke symptoms are still treated with thrombolytic therapy and majority of them recover with favorable outcomes at 90 days, but there is room to identify avenues to further enhance their outcomes. We aimed to investigate the risk factors associated with the unfavorable outcome at 90 days after thrombolysis for acute minor ischemic stroke (AMIS).

Methods:
152 consecutive patients presented with AMIS (NIHSS ≤3) and received intravenous alteplase between December 2012 and February 2017. Baseline clinic-demographic, characteristics and laboratory tests were recorded. Unfavorable outcome was defined as modified Rankin Scale (mRS) of 2-6 at 90 days. Univariate analysis followed by multivariate analysis was used to identify risk factors for unfavorable outcome. A receiver operating characteristic curve was used to evaluate the predictive value.

Results:
113 out of 152 patients (74%) were included in the final analysis, age 59 (53-67), 72.6% men. 32 patients (28.3%) experienced unfavorable outcomes. After adjusting for covariates, only serum glucose level on admission remained an independent factor for unfavorable outcome (OR 1.43, 95% CI: 1.10-2.72,
p
=0.014), with a 0.617 predictive value for the unfavorable outcome.

Conclusions:
About 28% of patients with AMIS in this cohort had an unfavorable outcome at 3 months after thrombolysis. Addressing higher serum glucose level on admission may be a viable therapeutic strategy to improve prognoses in these patients.
Abstract WP77: Effect of Concurrent Coil Embolization on Delayed Spontaneous Aneurysm Rupture Following Flow Diverter Placement
Authors: Kicielinski Kimberly P , Deveikis John , Harrigan Mark ,   Flow Diversion and Coils Consortium
Published: October 2018

Objective:
Delayed spontaneous aneurysm rupture is an uncommon but well recognized complication following flow diverter placement for the treatment of intracranial aneurysms. Concurrent coil embolization of the aneurysm along with flow diverter deployment is commonly used, under the assumption that coiling reduces the risk of delayed rupture. However, concurrent coiling adds expense and time to the procedure, and it is not known whether concurrent coiling actually reduces the risk of delayed rupture.

Methods:
This is a retrospective case-control study. Twelve centers provided data on patients with unruptured internal carotid artery aneurysm ≥10mm undergoing treatment with flow diversion. Cases were identified as those experiencing delayed spontaneous aneurysm rupture ≤ 30 days after treatment and each case was matched to five control patients not experiencing rupture. The rate of coil placement as well as data on demographics, medical history, aneurysm characteristics, and procedural details were collected.

Results:
Seven cases of delayed spontaneous rupture were identified, four of which were fatal. The interval between procedure and rupture ranged from 0-10 days, with a mean of 2.7 days. Cases and controls did not differ significantly in sex, smoking history, family history of aneurysm, aneurysm laterality, or size. Patients with delayed ruptures were more likely to have aneurysm occlusion at the end of the case (p=0.049). The rate of coil usage was 22% for both cases and controls. The odds ratio that coils protect against delayed rupture is 1.00 [CI 0.24, 4.96].

Conclusions:
This study suggests that concurrent coil embolization does not reduce the risk of delayed rupture of aneurysms treated with flow diversion.
Abstract WP81: Clinical Outcomes of Unruptured Intracranial Arterial Aneurysm Treatment in the US
Authors: Lee Seon-Kyu , Yuan Cindy , Karrison Theodore
Published: October 2018

Introduction:
The decision for active intervention for unruptured intracranial aneurysm patients are challenging due to most unruptured intracranial aneurysm patients are asymptomatic and they are reasonably healthy, but the procedure related risks such as stroke and mortality cannot be ignored. Selected high volume centers’ outcomes can potentially mislead the decision making process. Thus we aim to review the real-world clinical outcome of unruptured intracranial aneurysm treatment through a large national database.

Methods:
Unruptured intracranial aneurysm patients (18 to 86 years) from the 2007 to 2013 National Inpatient Sample Data were analyzed. Clinical outcomes evaluated include mortality, stroke, combined mortality and stroke, discharge home rate and complications except for mortality and stroke (M&S). Comparison of clinical outcomes between coiling and clipping were made through multivariate logistic regression and propensity-score matching. Also, hospital volume effects and over time trend of clinical outcomes per each intervention were analyzed.

Results:
Among 54,202 unruptured intracranial aneurysm patients, 37,050 (68.3%) were not treated, and either clipping or coiling was performed in 17,077 (31.5%). 6,120 (35.8%) patients had clipping and coiling was performed in 10,957 (64.16%). Unadjusted overall mortality, stroke, discharge home rate and complications except M&S were 0.5%, 3.27%, 2.2%, 84.24% and 11.05%, respectively. Coiling was favored for stroke and discharge home rate (p<0.05). Mortality rate was favored clipping but not statistically significant (p>0.05). Complications except M&S favored clipping and was statistically significant (p<0.05). Increasing hospital volume showed higher discharge home rate for both coiling (p=0.032) and clipping (p=0.000), and decreased mortality (p=0.009) in coiling. From 2007 to 2013, stroke rates showed statistically significantly reduced over time on clipping cohort.

Conclusion:
Active interventions on unruptured intracranial aneurysm showed very low overall mortality. However, coiling showed lower stroke rate and higher home discharge rate than clipping. There was no significant difference in mortality between coiling and clipping.
Abstract WP83: Sex Differential in 15-Hydroxyprostaglandin Dehydrogenase Levels in the Lumen of Human Intracranial Aneurysms
Authors: Chalouhi Nohra , Jabbour Pascal , Starke Robert M , Zanaty Mario , Torner James , Nakagawa Daichi , Hasan David
Published: October 2018

Background:
Aspirin is a promising medical therapy for the prevention of intracranial aneurysm (IA) rupture. Recently, we found that men have a better response to aspirin than women. The purpose of this study was to determine whether a sex differential exists in the level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the lumen of human IAs.

Methods and Results:
Consecutive patients undergoing coiling or stent-assisted coiling for a saccular IA at our institution were enrolled. Two samples (A and B) were collected from IA lumens and the plasma level of 15-PGDH was measured using an ELISA-based method. The study included 38 patients, with 20 women and 18 men. Women and men were comparable with respect to baseline characteristics. In samples A, the mean plasma concentration of 15-PGDH in IA lumens was significantly higher in men (75.8±13.8 ng/ml) than women (51.2±6.4 ng/ml, p<0.0001). Similarly, in samples B, the mean plasma concentration of 15-PGDH in IA lumens was significantly higher in men (75.5±12.9 ng/ml) than women (49.4±11.8 ng/ml, p<0.0001). Likewise, when mean values of samples A and B were compared, the mean plasma concentration of 15-PGDH in IA lumens remained significantly higher in men (75.6±12.2 ng/ml) than women (50.3±7.4 ng/ml, p<0.0001).

Conclusions:
Higher enzyme levels of 15-PGDH consistently exist in the lumen of IAs of men compared with women. This observation could explain why aspirin confers better protection against IA rupture in men than in women. The susceptibility of an individual to aspirin may differ according to the level of 15-PGDH.
Abstract WP85: Infectious Intracranial Aneurysm During Cardiac Valve Repair
Authors: Rice Cory J , Cho Sung-Min , Zhang Lucy , Wisco Dolora , Hussain M. Shazam , Uchino Ken
Published: October 2018

Introduction:
A complication of infectious endocarditis (IE) is infectious intracranial aneurysm (IIA, or mycotic aneurysm). Diagnosis and resolution of IIA prior to cardiac valve repair in IE patients is thought to reduce the risk of IIA rupture during perioperative anticoagulation. We report a series of patients undergoing cardiac valve replacement with unresolved IIAs.

Methods:
The study was designed as a review of medical records at a single tertiary referral center from 2011-2016. A total of 618 patients with infective endocarditis undergoing cerebral angiogram were reviewed. Patients with secured unruptured IIA prior to surgery were compared to patients with unsecured unruptured IIA prior to surgery. Perioperative intracranial hemorrhage and death were compared between the two groups.

Results:
Of 27 patients with IIA undergoing valve surgery, 7 (26%) had preoperative unsecured aneurysms, while 20 (74%) had angiographically resolved or occluded aneurysms (14 resolved by endovascular occlusion, 6 by antibiotics). The 7 unsecured IIAs were not resolved for various reasons (3 had high risk of vessel sacrifice, 1 had small size, 3 had patient clinical instability). Median time from last angiogram to valve surgery was 7 days (IQR 2-8) in the unsecured group, and 5.5 days (IQR 3-9) for secured group. There was no postoperative subarachnoid hemorrhage (SAH) or aneurysmal rupture seen in either group. Perioperative hemorrhagic transformation of a subacute ischemic stroke was observed in one patient in each group (14% versus 5%, p=0.46). There were no deaths or further bleeding in the unsecured aneurysm group.

Conclusion:
There was no post-operative death or SAH seen in seven patients undergoing cardiac valve surgery with unsecured IIA.
Abstract WP86: Korean Red Ginseng Protects Against Long-term Sensorimotor Deficits After Ischemic Stroke Through The Nrf2 Pathway
Authors: Liu Lei , Vollmer Mary K , Fernandez Victoria M , Dweik Yasmin , Kim Hocheol , Doré Sylvain
Published: October 2018

Introduction:
Nrf2 is an astrocyte-enriched transcriptional factor that serves as a key regulator of endogenous cellular defense systems against oxidative stress and inflammation. Korean Red Ginseng (Ginseng), one of the most widely used herbal medicines, has exhibited an encouraging protective efficacy against various neurological disorders in preclinical and clinical studies.

Hypothesis:
Our study aimed to determine whether Ginseng-pretreatment attenuates sensorimotor deficits and improves long-term recovery after ischemic stroke though the Nrf2 pathway activation by preferentially altering reactive astrogliosis.

Methods:
WT and Nrf2
-/-
mice were pretreated with Ginseng via gavage once daily for 7 days prior to permanent distal middle cerebral artery occlusion (pdMCAO). Neurobehavioral tests were performed to assess sensorimotor deficits and long-term recovery over 28 days, lesion volumes were determined, and immunohistochemical analysis was used to characterize the astrocytic and microglial activation in early stage of ischemic stroke onset (0-3 days). Specific Nrf2 downstream targeted antioxidant genes expressions were assessed by Western Blot.

Results:
We first established a novel method that can accurately assess long-term sensorimotor deficits after pdMCAO. Second, we revealed that Ginseng-pretreatment decreased sensorimotor deficits and promoted long-term recovery, reduced ischemic lesion volume (8.03±1.74% vs 12.62±0.81% on day 3), attenuated reactive astrogliosis at a spatiotemporal pattern but not microglia activation, and enhanced the induction of Nrf2-downstream proteins after ischemic injury in WT mice, which was essentially abolished in Nrf2 knockouts. Of interest, Nrf2 deficiency exacerbated the deterioration of ischemic damage.

Conclusion:
Ginseng-pretreatment protects against acute ischemic sensorimotor deficits and promotes long-term recovery through Nrf2 activation by preferentially altering the spatiotemporal reactive astrogliosis. These findings indicate that oral consumption of Ginseng in humans may have similar robust efficacy of pre-ischemic intervention that impedes the ischemic cascade and ultimately facilitates functional recovery.
Abstract WP9: Direct Aspiration (ADAPT) and Primary Stent Retriever Thrombectomy for Acute Ischemic Stroke: A Systematic Review of Radiographic and Clinical Outcomes in 3339 Patients
Authors: Primiani Christopher T , Mokin Maxim , Siddiqui Adnan H , Turk Aquilla S , Levy Elad I , Linfante Italo
Published: October 2018

Introduction:
Endovascular stroke therapy has been revolutionized by the advent of modern devices for thrombectomy. It remains to be determined what is the most safe and effective way to perform stroke thrombectomy. The two most common approaches to thrombectomy currently include: 1-direct aspiration with the additional use of a stent retriever if needed (ADAPT), 2 - primary stent retriever thrombectomy. We aimed to compare radiographic and clinical outcomes in patients with acute stroke from large vessel occlusion (LVO) treated with these two approaches.

Methods:
Using the PubMed database, we searched for studies that included patients with acute ischemic stroke from LVO treated with direct aspiration (ADAPT) or primary stent retriever thrombectomy. The literature search included 294 studies, excluding 122 manuscripts. Statistical analysis was performed on 36 publications with a total of 2656 patients that underwent thrombectomy using a stent retriever device and 11 publications with a total of 683 patients that underwent thrombectomy using ADAPT. We compared the proportions of patients with successful recanalization, favorable functional outcomes, intracranial hemorrhage, mortality rates and occurrence of distal embolization in the two treatment groups by calculating chi
2
and confidence intervals for odds ratios.

Results:
3339 patients from 47 publications were included in final analysis. There was no difference in age (p=0.7625, 95% CI -2.91–3.94), NIHSS (p=0.1135, 95% CI -3.55-0.39), the use of intravenous thrombolysis (p=0.9631, 95% CI -29.46-30.85), or location of occlusion (internal carotid artery, middle cerebral artery or posterior circulation; p=0.9679) between the two groups. We found no difference in rates of successful recanalization TICI 2b/3 (79.9% with ADAPT vs. 74.9% with primary stent retriever; p=0.4771, 95% CI -0.091-0.191) or good clinical outcome at 3 months defined as mRS 0-2 (51.0% with ADAPT vs. 46.8% with primary stent retriever; p=0.4814, 95% CI -0.161-0.077).

Conclusion:
According to our systematic review, endovascular treatment with direct aspiration (ADAPT) and primary stent retriever thrombectomy approaches results in similar radiographic and clinical outcomes in patients with acute stroke from LVO.
Abstract WP92: Stroke Induces Long-term Central Nervous System Specific T Cell Responses
Authors: Selvaraj Uma Maheswari , Kong Xiangmei , Plautz Erik J , Mirø Francesc , Urra Xabier , Ortega Sterling , Planas Anna M , Stowe Ann M
Published: October 2018

Introduction:
Stroke patients with higher lymph node antigen presentation of neuronal antigens MAP2 and NMDA receptor subunit 2A (GluN2A) exhibited smaller infarctions at day 7 and better long-term improvement at 3 months. We therefore hypothesized that T cell responses to MAP2 and GluN2A have a neuroprotective profile after stroke in mice. We previously found that stroke induced higher splenic CNS-autoreactive T cells compared to sham mice (10/12 mice vs 4/7 mice). Furthermore, CD8 T cells (10/12 mice) had higher GluN2A-specific responses compared to CD4 T cells (4/12 mice). However, it remains unclear if stroke induces long-term T cell autoimmune responses, and if these are relevant to functional recovery after stroke.

Methods:
Male C57BL/6 mice (B6, Jackson Labs, 8-10 weeks) were subjected to 60 mins transient middle cerebral artery occlusion. Spleens were harvested 8 and 10 days post-stroke, stained with CFSE, and cultured with GluN2A and MAP2 peptides for 6 days. Cell cultures were stained with fluorescently-tagged antibodies and quantified by flow cytometry. Another cohort of mice were euthanized 14 and 30 days after stroke, and immune cell subpopulations in the brain were quantified using flow cytometry.

Results:
GluN2A-15 peptide-specific CD4 (17% and 4%) and CD8 (35% and 22%) splenic T cells primarily produced pro-inflammatory cytokines TNF-α and IFN-γ, respectively. Animals with lower infarct volumes had higher number of IL-10- and TNF-α-producing neuronal antigen-specific CD4 T cells (R
2
=0.95 and R
2
=0.86) and CD8 T cells (R
2
=0.7 and R
2
=0.95) in spleen, respectively. Post-stroke mice also had higher numbers of CD4 T cells and CD8 T cells in their ischemic hemisphere compared to the contralateral hemisphere at 14 days (19-fold, p<0.0001 and 8-fold, p=0.0084) and 30 days (8-fold, p=0.0031 and 7-fold, p=0.0013) after stroke respectively.

Conclusion:
We previously identified GluN2A and MAP2 peptides that elicit strong positive responses from CD4 and CD8 T cells at 8 and 10 days post-stroke. We now show that there are long-term CD4 T cells and CD8 T cells responses in the ischemic hemisphere post-stroke. Future experiments will determine cytokine profile of neuronal antigen-specific cells in brain and establish if they are protective after stroke.
Abstract WP94: MCC950, a Novel Selective NLRP3-inflammasome Inhibitor Provides Protection in a Murine Model of Focal Cerebral Ischemia
Authors: Ismael Saifudeen , Zhao Liang , Ishrat Tauheed
Published: October 2018

Background and Hypothesis:
Activation of the NOD-like receptor protein (NLRP3) inflammasome has been postulated in mediating inflammatory responses to brain damage during ischemic reperfusion (I/R) injury. In this study, we therefore hypothesized that MCC950, a selective NLRP3-inflammasome inhibitor provides protection in a mouse model of ischemic stroke.

Methods:
Transient focal cerebral ischemia was induced by 60 min middle cerebral artery occlusion (MCAO) followed by 23 h reperfusion in mice. MCC950 (50 mg/kg) or saline was administered intraperitoneally at 1 h and 3 h post-occlusion. After 24 h of I/R, mice were tested for neurobehavioral outcome and were sacrificed for infarct size analysis and estimation of inflammasome and apoptotic markers.

Results:
MCC950-treated mice showed a substantial reduction (28%) in the infarct size (% contralateral hemisphere) and edema (29%) compared to saline controls. Further, administration of MCC950 after MCAO reduced the brain hemorrhage compared to saline treated mice. MCC950 treatment significantly (P<0.05) inhibited the expression of NLRP3-inflammsome components, and suppressed inflammatory and apoptotic damage (
Table 1
).

Conclusion:
Taken together, these data indicate that inhibition of NLRP3-inflammasome with MCC950 may have therapeutic potential in ischemic stroke model. Further investigations into the role and mechanisms of NLRP3 inhibition are needed to determine whether it can be an effective therapy for stroke patients.