bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP573: Nrf2 Activation With Sulforaphane Reduces Post-Stroke Cognitive Impairment in Mice
Authors: Li Qianqian , Yang Tuo , Li Senmiao , Zhang Feng
Published: January 2019

Introduction:
Post-stroke dementia is common in stroke patients and oxidative stress may contributes to its pathogenesis. Nuclear factor erythroid 2 related factor (Nrf2) is a master transcription factor regulating the expression of a series of anti-oxidative enzymes. Sulforaphane (Sfn) is a dietary Nrf2 activator rich in cruciferous vegetables. This study aims to test our hypothesis that Sfn treatment reduces white matter injury and cognitive impairment after ischemic stroke.

Methods:
Adult male and female wildtype and Nrf2 knockout mice were randomly and blindly assigned into sham, vehicle, and Sfn-treatment groups (n=8-10). Stroke was induced in mice by direct coagulation of the left distal middle cerebral artery and permanent ligation of left common carotid artery occlusion. Sfn in PBS was administered by intraperitoneal injection (20 mg/kg) starting after the surgery and subsequently every other day for 5 weeks. Sensorimotor deficits were assessed using Rota-rod and foot fault tests 3-35 d and cognitive impairment were determined using Morris water maze test 29-34 d after surgery. Brain tissue loss was assessed at 35 d after surgery. In vitro, primary neuronal cultures were treated with vehicle or Sfn (1.5 μM) and chronic hypoxia/ischemia was then induced by incubation with cobalt chloride (250 μM) for 48 h. Neuronal viability was assessed with MTT assay.

Results:
Wildtype mice exhibited significantly sensorimotor deficits and long-term cognitive impairment after stroke. Sfn treatment alleviated these sensorimotor deficits, long-term cognitive impairment, and brain infarct size in wildtype mice. Nrf2 knockout mice also exhibited significantly sensorimotor deficits and long-term cognitive impairment after stroke; however, Sfn treatment didn’t affect these sensorimotor. In cultures, neuronal survival rate in Sfn group was significantly higher compared with vehicle group. Nrf2 knockdown with Nrf2-shRNA abolished the protective effects of Sfn.

Conclusion:
Sfn treatment reduces cognitive impairment after stroke in mice in a Nrf2 depended manner. Nrf2 may be a promising target to reduce post-stroke cognitive impairment.
Abstract TP582: A Multi-Site Validation of MRI Biomarkers of Vascular Leak and Hemorrhage for Forthcoming Clinical Trials
Authors: Hobson Nick , Polster Sean , Turley Dallas , Cao Ying , Flemming Kelly , Huston John , Morrison Leslie , Selwyn Reed , Girard Romuald , Hanley Daniel , Koskimaki Janne , Shenkar Robert , Stadnik Agnieszka , Carroll Timothy , Awad Issam
Published: January 2019

Background:
Cerebral cavernous malformation is a genetic neurovascular disorder causing aberrant angiogenesis and lesion development within capillary beds. Lesions exhibit impaired endothelial barrier function, causing blood-brain barrier leakage and hemorrhage. Quantitative MRI biomarkers (dynamic contrast-enhanced quantitative permeability (DCEQP) and quantitative susceptibility mapping (QSM)) have been shown to correlate with CCM disease progression as measures of barrier leakage and hemorrhagic iron deposition, and there is interest in utilizing these biomarkers as endpoints in clinical trials. However, their consistencies across multiple platforms and institutions has not yet been rigorously verified.

Materials and Methods:
Instruments used were a 3T Philips Ingenia at University of Chicago and a 3T Siemens Prisma at Northwestern University. QSM was assessed by five balloons filled with varying concentrations of MultiHance, corresponding to magnetic susceptibilities of 0, 0.1, 0.2, 0.4, and 0.8, surrounded by an agarose gel. Permeability was assessed by the injection of a bolus of MultiHance through a coiled hose inside a water-filled shell, and the consistency of the peak-to-peak ratio of the curves at the input and output was measured. Each biomarker was assessed by accuracy (to expected values, Pearson correlation), precision (between repeated measurements, paired t-test), and reproducibility (between instruments, paired t-test).

Results:
QSM measured with an accuracy of r
2
= 0.997 on the Philips Achieva and r
2
= 0.999 on the Siemens Prisma. Each scanner had adequate precision between measurements, showing no significant difference by a paired t-test (p = 0.66 Achieva, p = 0.45 Prisma), and the reproducibility between scanners also showed no significant difference (p = 0.89). The peak-to-peak ratio on DCEQP scans was accurate (r
2
= 0.998), precise between measurements (p = 0.54), and repeatable between instruments (p = 0.49).

Conclusion:
Quantitative imaging biomarkers DCEQP and QSM are accurate, consistent across multiple measurements, and between platforms and will be useful for future clinical trials in CCM.
Abstract TP587: Microsurgery Treatment Rate for Unruptured Cerebral Arteriovenous Malformations is Increased post-ARUBA
Authors: Birnbaum Lee A , Straight Matthew , Lacci John V , de Leonni Stanonik Mateja , Mascitelli Justin R , McDougall Cameron M , Caron Jean-Louis R
Published: January 2019

Background:
The ARUBA trial reported medical management was superior to intervention for unruptured cerebral arteriovenous malformations (cAVMs); however, open excision was underrepresented in the intervention arm. We investigated whether the ARUBA trial results influenced treatment modality rates for unruptured cAVMs within the United States.

Methods:
We queried the National Inpatient Sample (NIS), the largest all-payer inpatient care database in the United States, and identified 2,028 patients that underwent treatment for unruptured cAVMs between January 2011 and September 2015. All screened subjects had AVM ICD-9-CM diagnosis code 747.81 (anomalies of cerebrovascular system) and were excluded based on hemorrhage codes 430 (SAH) and/or 431 (ICH). ICD-9-CM principal procedure codes were used to identify treatment modalities: endovascular (39.72), open excision (01.59), and stereotactic radiosurgery (SRS) (92.30-.39). Univariate logistic regression was used to compare treatment rates for each modality before and after two ARUBA time points: 1) European Stroke Conference (ESC) presentation May 2013 and 2) The Lancet publication February 2014.

Results:
When unruptured cAVMs were treated, the rate of open excision was greater after, compared to before, the May 2013 ARUBA presentation (OR 1.22, p<0.05). Additionally, a trend for open excision was noted using the February 2014 publication date (OR 1.20, p=0.054). Endovascular and SRS did not show significant differences in treatment rates at either time point.

Conclusions:
Unruptured cAVMs within the NIS database that underwent treatment had open excision significantly more after, compared to before, the ARUBA results were presented at the ESC. When using The Lancet publication date, a non-significant trend for open excision was noted but likely resulted from insufficient numbers in the post-Lancet publication group. Our findings suggest that the ARUBA trial has influenced current treatment modality rates for unruptured cAVMs captured within the NIS.
Abstract TP60: Comparison of Predicted vs. Actual Enrollment Into the NIH StrokeNet DEFUSE 3 Trial: Effectiveness of a Population-Based Epidemiology Feasibility Assessment in Improving Enrollment Into Clinical Trials
Authors: Kleindorfer Dawn O , Moomaw Charles J , Mlynash Michael , Broderick Joseph P , Khatri Pooja , Saver Jeffrey L , Alwell Kathleen , Kemp Stephanie , Janis Scott , Moy Claudia , Woo Daniel , Flaherty Matthew L , Ferioli Simona , Adeoye Opeolu , Kissela Brett M , Lansberg Maarten , Albers Greg
Published: January 2019

Introduction:
The NIH StrokeNet trial network aims to improve recruitment and retention into stroke clinical trials. In addition to StrokeNet infrastructure, a population-based feasibility assessment is performed prior to submission to NIH. We sought to describe the impact of this assessment on the design and recruitment efficiency of the DEFUSE 3 trial, the first trial to be proposed and completed entirely within NIH StrokeNet.

Methods:
We identified all ischemic stroke (IS) cases in the region in 2005 by screening all local hospital ICD-9 codes 430-436 among residents of the Greater Cincinnati/Northern Kentucky (GCNK) region, a biracial population of 1.3 million through chart abstraction and physician review. Initial proposed, and final revised DEFUSE 3 trial entry criteria were analyzed for population-based eligibility.

Results:
DEFUSE 3 is an acute reperfusion ischemic stroke (IS) trial conducted at 38 US centers between 5/16-5/17. Initial inclusion/exclusion criteria proposed by trial PIs predicted that 2.4% (46 of 1843 in 2005) of IS patients would be eligible for DEFUSE-3. After criteria revision, this increased to 4.0% (74/1843). Four exclusion criteria were changed by study PIs after receiving feedback: upper age limit, baseline disability, time since last seen normal, and NIHSS (Table). Overall, 57% (104/182) of enrolled patients qualified via the broadened study entry criteria. In subsequent implementation, the trial randomized 0.47 patients per site per month which was nearly twice the expected enrollment rate.

Conclusion:
Feedback from formal epidemiologic feasibility assessment to trial investigators during multicenter clinical trial design led to a broadening of entry criteria, and more than half of eventually enrolled patients were eligible only because of the expanded criteria. Iterative trialist-epidemiologist interaction is a promising approach to improve multicenter clinical trial planning and efficient study conduct.
Abstract TP75: Distal Hyperintense Vessel Sign on FLAIR as a Predictor of Recurrent Stroke in Intracranial Arterial Stenosis
Authors: Saherwala Ali A , Salahuddin Hisham , Jeelani Faraz , Campbell Joel , He Henry , Khan Nadeem , Moore William , Pinho Marco , Shang Ty
Published: January 2019

Introduction:
The distal hyperintensity vessel (DHV) on FLAIR images is a linear/serpentine shaped hyperintensity that is seen not infrequently in acute ischemic stroke or transient ischemic attack (TIA). Previous studies reported that DHV could predict large vessel occlusion or stenosis and correlate with outcome. The purpose of this study is to evaluate whether presence of DHV is associated with high risk of recurrent ischemic stroke in symptomatic intracranial atherosclerotic severe stenosis.

Methods:
We retrospectively reviewed patients who presented with ischemic stroke or TIA to a University-affiliated Comprehensive Stroke Center from 2010 to 2015. Patients with etiology due to 70-99% atherosclerosis stenosis of intracranial carotid artery or middle cerebral artery were enrolled. Patients with atrial fibrillation or other cardiac embolism, ipsilateral extracranial carotid artery > 50% stenosis, artery dissection, hypercoagulation state, Moyamoya or other non-atherosclerotic vasculopathy were excluded. FLAIR images were reviewed by two neuroradiologists and one vascular neurologist for the presence of DHV. A quantitative scoring system of maximum 7 based on ASPECTS distribution is applied to grade the extent of DHV. The primary measure is ischemic stroke in the territory of qualifying artery during follow up. Univariate and multivariate logistic regressions were used to identify predictors of recurrent ischemic stroke.

Results:
Out of 106 patients enrolled, 53 (50%) were found to have DHV (median score of 3.03 ± 1.47). There were more non-whites in DHV group than in non-DHV group (p=0.0314). During follow up, 17 (32%) patients in DHV group had recurrent ischemic stroke compared to 6 (11%) patients in non-DHV group (p=0.0087). The presence of DHV was the only factor associated with recurrent ischemic stroke with OR of 3.074 (95% CI 1.079 - 8.761, p=0.036) by multivariate logistic regression. There is a tendency of high risk of recurrent ischemic stroke for high DHV score with Pearson Correlation R value of 0.7.

Conclusions:
The presence of DHV is associated with higher risk of recurrent ischemic stroke in symptomatic intracranial atherosclerotic severe stenosis. Confirmation of this finding in large prospective studies is needed.
Abstract TP78: Density Analysis of Hyperdense Middle Cerebral Artery Sign for Detection of Embolic Stroke of Undetermined Source and Prediction of Successful Reperfusion Following Endovascular Therapy
Authors: Siepmann Timo , Abramyuk Andrej , Moustafa Haidar , Prakapenia Alexandra , Pallesen Lars-Peder , Barlinn Jessica , Linn Jennifer , Puetz Volker , Barlinn Kristian
Published: January 2019

Introduction:
Density of hyperdense middle cerebral artery sign (HMCAS) quantified via Hounsfield units (HU) on CT may predict clot composition and stroke TOAST subtype, with clots from cardioembolism displaying lower HMCAS densities due to fibrin predominance than erythrocyte-dominant clots originating from large artery atherosclerosis (LAA).

Hypothesis:
We hypothesized that embolic stroke of undetermined source (ESUS) is linked to higher density of HMCAS due to its high probability of a cardiac source and that HMCAS as a surrogate marker of clot composition predicts successful reperfusion following endovascular therapy (EVT).

Methods:
We analyzed data from an ongoing prospective observational study (since 01/2016) in consecutive patients with acute ischemic stroke (AIS) undergoing EVT for proximal occlusion of the middle cerebral artery (MCA) detected on CT-angiography and confirmed on digital subtraction angiography. Stroke subtypes were determined according to TOAST and ESUS criteria. On thin-slice (1.5mm) non-contrast CT, a blinded neuroradiologist assessed average and maximum HU values for HMCAS. Multiple regression analyses were undertaken to explore the association of HMCAS density normalized for contralateral MCA (HMCAS ratio) with stroke subtypes and major reperfusion (TICI 2b/3) following EVT.

Results:
In this interim analysis 110 out of 253 patients were included (55.1% females, ages 74 [64-80], median [IQR], baseline NIHSS 17 [13-20], 76 with IVT before EVT) of which 19 (17.8%) had ESUS, 65 (60.8%) had cardioembolism and 23 (21.5%) had LAA. Density analyses showed HMCAS ratios of 1.26 ± 0.22 (mean ± SD) in the entire cohort with no differences among subgroups (ESUS: 1.19 ± 0.26, LAA: 1.24 ± 0.25, cardioembolic stroke: 1.29 ± 0.19, p = ns), the latter being also true for HMCAS ratios of maximum HU values and absolute HU values (p = ns). On multivariate regression model adjusted for intravenous tPA and onset to groin puncture time, HMCAS average ratio did not predict major reperfusion (per 1-unit HU increase: 2.13; [0.25-18.29], OR [95% CI]) or stroke subtype.

Discussion:
Density analysis of HMCAS appears not to be helpful in detection of ESUS, diagnostic discrimination between stroke subtypes, or prediction of reperfusion following EVT.
Abstract TP82: Long Distance of Delayed-Contrast Filling Sign on Four-Dimensional CT Angiography Associates With Cardiogenic Embolism
Authors: Zhou Ying , Xu Chao , Zhang Ruiting , Shi Feina , Liu Chang , Yan Shenqiang , Yan Shenqiang , Jiaerken Yeerfan , Jiaerken Yeerfan , Zhang Minming , Lou Min
Published: January 2019

Objectives:
We hypothesized that the presence of delayed contrast filling sign (DCFS), which possibly reflected contrast penetration into the thrombus, was associated with stroke etiology with different clot component. We then aimed to evaluate its predictive value for stroke subtype in acute ischemic stroke (AIS) patients with M1 segment of MCA (MCA-M1) occlusion.

Methods:
We retrospectively included MCA-M1 occlusion patirnts who underwent CTP within 8 hours post-stroke onset. DCFS was defined as the presence of contrast diffusion through the thrombi after the arterial peak phase on 4D-CTA derived from CTP. We measured the straight distance from the origin site of MCA-M1 to the proximal occlusion site on the arterial peak phase (distance
peak
), and the maximum distance among every continuous phase after the arterial peak phase (distance
maximum
). We calculated the distance of DCFS as distance
maximum
-distance
peak
and investigated its value for predicting the stroke subtype.

Results:
Among 144 included patients, 80 were in cardiogenic embolism (CE) group, 31 in large artery atherosclerosis (LAA) group, and 33 in undetermined etiology (UE) group. The median distance of DCFS was 1.3mm, 0.4mm and 0.6mm in CE, LAA and UE groups, respectively. CE group had a longer distance of DCFS than LAA group (
p
=0.001). The optimal cut-off value of distance of DCFS for predicting CE was 1.5mm. The sensitivity, specificity, positive predictive value and negative predictive value of a distance of DCFS>1.5mm for predicting CE were 55.0%, 87.1%, 90.0% and 38.0%. Moreover, a distance of DCFS>2.0mm had a specificity of 100% for predicting CE. Figure A-E shows a patient with DCFS>1.5mm, and Figure F-J shows a patient with DCFS<1.5mm.

Conclusion:
Long distance of DCFS was associated with cardiogenic embolism, which could provide clues of stroke etiology and help the pattern selection of reperfusion therapy in future.
Abstract TP83: Predicting Clinical Outcomes of Acute Ischemic Stroke Due to Large Vessel Occlusion: The Approach to Utilize High-dimensional Neuroimaging Data With Deep Learning
Authors: Nishi Hidehisa , Oishi Naoya , Ishii Akira , Chihara Hideo , Ogura Takenori , Ishibashi Ryota , Ando Mitsushige , Sadamasa Nobutake , Ohta Tsuyoshi , Kai Yasutoshi , Yamao Yukihiro , Okawa Masakazu , Kikuchi Takayuki , Hatano Taketo , Nakahara Ichiro , Miyamoto Susumu
Published: January 2019

Introduction:
Although the clinical outcomes of acute ischemic strokes associated with large vessel occlusion have substantially improved by mechanical thrombectomy, the good clinical outcomes were achieved only in 40-50% of the treated patients. In the clinical practice, neuroimaging information is usually interpreted into scalar data, such as ASPECTS or lesion volume. The detection of prognostic factor might lead to the patient selection appropriate for intervention.

Hypothesis:
We hypothesize that more appropriate information could be directly deduced from high-dimensional neuroimaging data using deep learning algorithm.

Methods:
All patients with anterior circulation ischemic stroke treated with mechanical thrombectomy at our institution between December 2013 and December 2017 were included. The purpose of each model was designed to predict good clinical outcome, which was determined as modified Rankin Scale 0 to 2 at the 90-day follow-up. The “low-dimensional” model used logistic regressions with DWI-ASPECTS (ASPECTS model) or infarct volume (Lesion volume model), both features were derived from on-arrival diffusion weighted image (DWI). The “high-dimensional” model used 3D convolutional neural network (3D-CNN). The input to the 3D-CNN model was the whole DWI volume data. All models were evaluated and compared for the accuracy with 5-fold cross validation.

Results and Conclusions:
One hundred sixty-six patients were included for the analysis. The 3D-CNN model showed the highest accuracy 0.70±0.05 (mean±SD), compared with 0.59±0.07 of ASPECTS model and 0.53±0.05 of Lesion volume model, and was signify better than the other two models (p=0.008 with ANOVA). Although this was a preliminary analysis with limited number of patients, it is suggested that deep learning model can retrieve more valuable information from neuroimaging data than conventional low-dimensional neuroimaging factors.
Abstract TP92: When Less is More: Do We Need Advanced Perfusion Neuroimaging Prior to Mechanical Thrombectomy?
Authors: Koneru Sitara , Khan Shazli , Cole Kimberly , Jumaa Mouhammad A , Zaidi Syed F
Published: January 2019

Objective:
To assess whether the choice of pretreatment neuroimaging has an impact on clinical outcomes following mechanical thrombectomy (MT).

Background:
Most MT trials required advanced neuroimaging including either CT or MR based perfusion studies for patient selection prior to randomization. However, in practice, centers may offer MT based on favorable findings (ASPECT score > 6) on non-contrast head CT (HCT) ± CT angiogram (CTA). We compared outcomes between patients who underwent MT based on HCT ± CTA (HCT- group) versus additional including CT or MR perfusion scan (HCT+ group).

Design/Methods:
Case records of all patients who underwent MT at our center between Jun 2012 - Jun 2017 were reviewed. Patient demographics, risk factors, presentation, pretreatment scan findings, treatment times and clinical outcomes were compared. Favorable outcome is defined as mRS of 2 or less at 90-days.

Results:
A total of 528 patients were identified, of which 46.4% were male. There were 385 (72.9%) patients who underwent MT based on findings on HCT or CTA (HCT-); while the remaining 143 (27.1%) also underwent additional CTP (121/528; 22.9%) or MRI perfusion (22/528; 4.2%) prior to MT (HCT+). Median age (73 vs 72, p=0.1) and baseline ASPECT scores (8.4 vs. 8.3, p=0.5) were comparable. The HCT- patients had higher NIHSS (17.8 vs. 15.3, p<0.01) and presented earlier with faster onset-to-onsite arrival time (241 vs. 476 minutes, p<0.01). Also, rate of TICI 2b/3 recanalization was higher in the HCT- group (82.8 vs 71.5, p<0.01); however favorable outcome rates were comparable (44.6 vs 47.4, p=0.6).

Conclusions:
Our findings suggest that HCT ± CTA based MT selection may achieve similar outcomes as compared to more advanced perfusion based neuroimaging protocols. Further prospective studies are warranted.
Abstract TP96: Low Cerebral Blood Flow Grade Based on Dynamic Magnetic Resonance Imaging Predicts Neurological Deterioration in Patients Treated Without Thrombectomy Because of Low NIHSS Score Despite the Carotid or Middle Cerebral Artery Occlusion
Authors: Kawakami Tetsuro , Yoshioka Kazuhiro , Tanno Yuhei , Nakai Noriyoshi , Mori Takahisa
Published: January 2019

Introduction:
Most of patients with mild neurological symptoms despite the carotid or middle cerebral artery occlusion (CO or MCAO) are treated without thrombectomy because of no its evidence.However, among them, some patients’ neurological symptoms deteriorate during hospitalization.

Methods:
We included in our retrospective study acute ischemic stroke patients 1) who were admitted to our institution between April 2011 and January 2018, 2) who could walk before stroke, 3) who underwent MR angiography(MRA), displaying occlusion of the internal carotid artery(ICA) or the M1 segment of the middle cerebral artery(MCA), 4) who presented low NIHSS scores of 4 or less and didn’t undergo thrombectomy.We evaluated patients’ baseline features, NIHSS scores on arrival and at discharge, and time-intensity curve (TIC)-cerebral blood flow (CBF) grade. TICs were generated on region of interests set at symmetrical positions of the bilateral MCA territories. According to the time to peak (TP) and the peak signal (PS) comparing the affected side(a) with the contralateral side(c), we defined (TPa/TPa) divided by (TPc/TPc) as CBF% and grade 1 as CBF% of less than 0.2, grade 2 as CBF% of 0.2 or more and CBF% less than 0.7 and grade 3 as CBF% of 0.7 or more. We defined patients with NIHSS at discharge higher than NIHSS on admission as Group Worse and defined others as Group Non-Worse.

Result:
Thirty-six patients met our inclusion criteria and were analyzed. The median age was 76.5 years, and 24 patients were men. Median NIHSS score on arrival and at discharge was 2 and 1. There were no patients with CBF grade 1, 8 patients with CBF grade 2 and 28 with CBF grade 3. There were 7 patients in Group Worse and 29 in Group Non-Worse.In Group Worse and Non-Worse, median age was 64 and 78 (ns), median NIHSS score at admission was 2 and 2 (ns), 4 patients and 4 patients in CBF grade 2 and 3 patients and 25 patients in CBF grade 3 (p<0.05)

Conclusion:
CBF grade based on dMRi is the significant predictor of neurological deterioration. In cases of CBF grade 2 due to the ICA or MCA occlusion, neurological symptoms probably deteriorate in 50% of patients during hospitalization without thrombectomy.
Abstract WMP11: Interhospital Transfer versus Direct Admission of Acute Stroke Patients Undergoing Endovascular Reperfusion Therapy: A Real-World Experience in Japan
Authors: Hayakawa Mikito , Sato Masayuki , Yoshimura Masataka , Tsurumi Arihito , Kawai Takuya , Kasuya Hiromichi , Ohashi Tomoo , Oshima Kosuke , Oshima Kosuke , Ito Yoshiro , Marushima Aiki , Kato Noriyuki , Matsumaru Yuji ,   RICOVERY study group
Published: January 2019

Introduction:
Interhospital transfer to endovascular-capable centers (ECCs) is reported to correlate with worse clinical outcome after endovascular stroke reperfusion therapy (ESRT). The aim of this study was to investigate the relationship between admission mode and functional outcome after ESRT in real clinical setting in Japan.

Methods:
The RICOVERY study retrospectively registered 575 patients with large vessel occlusion who were admitted to and underwent ESRT at 16 ECCs in Ibaraki prefecture, located just northeast of Tokyo, within 24 hours of onset between January 2015 and December 2017. We extracted patients without in-hospital stroke onset or recurrence and divided them into two groups: those with interhospital transfer (I group) and with direct admission to ECCs (D group). Favorable outcome (FO) was defined as a mRS of 0-2 at discharge. We additionally performed a subgroup analysis with patients with premorbid mRS of 0-2 and who underwent ESRT within 6 hours of onset.

Results:
A total of 483 patients (198 women, 75±11 years) was included. Intravenous thrombolysis was performed in 289 patients (60%). In the I group (n=69), median baseline NIHSS score was lower (17 vs 19, p=0.025) and the proportion of large-artery atherosclerosis was higher (19% vs 10%, p=0.025) compared with the D group (n=414). The rates of reperfusion (mTICI grade 2b/3) were similarly high in both groups (88% and 86%, respectively). Although median onset-to-puncture time (OPT) was longer in the I group than in the D group (240 min vs 185 min, p=0.01), no significant difference was shown in the rate of FO between the groups (28% vs 36%, p=0.197). In subgroup analysis, baseline NIHSS scores and stroke subtypes were similar between the I group (n=51) and the D group (n=273). Median OPT was longer in the I group than in the D group (220 min vs 160 min, p=0.005) as with the entire study cohort, and the rate of FO in the I group was lower than in the D group (24% vs 43%, p=0.01). After multivariate adjustment, interhospital transfer was a negative predictor of FO (Odds ratio, 0.343; 95% confidence interval, 0.158-0.747).

Conclusion:
In this Japanese real-world study, interhospital transfer was associated with delays of ESRT and lower chance of FO within a 6-hour time window.
Abstract WMP12: Endovascular Therapy in Acute Ischemic Stroke With M2 Occlusion
Authors: Chapman Emily , Morey Jacob , Hao Qing , Zhang Xiangnan , DeLeacy Reade , Fifi Johanna
Published: January 2019

Introduction:
Endovascular Therapy (EVT) has become standard care for selected acute ischemic stroke (AIS) patients with a proximal emergent large vessels occlusion (ELVO), such as occlusion in terminal ICA or M1 of MCA. It is not uncommon to have a M2 occlusion producing an unfavorable outcome; however, the data on EVT in AIS with M2 occlusion is limited. We sought to explore the clinical features, efficacy and safety of EVT in M2 occlusions.

Methods:
AIS patients with an ELVO who underwent EVT in a single academic center from January 2016 to May 2018 were consecutively included in our quality assurance database. The clinical characteristics, procedural features and clinical outcome were compared between M2 and M1/ICA occlusions using a t-test (Wilcoxon Test) and Fisher Exact Test.

Results:
Among 239 AIS patients, of which 43.9% were male, who received EVT, 179 patients had a M1 or ICA occlusion and 60 had a M2 occlusion. Compared with a M1/ICA occlusion, those with a M2 occlusion were older (age 74±13 vs 69±15 year old, p = 0.01), had a higher ASPECTS (median 9 vs 8, p = 0.012), and a lower NIHSS score (median 16 vs 19, p=0.01). These cohorts had a similar number of EVT passes (2.6 vs 3.0, p = 0.25) and time interval from last known well to groin puncture and final recanalization. Patients with a M2 occlusion had a trend of lower post-operative hemorrhage rate (including ICH and SAH, 24.1% vs 36.3%, p = 0.11) and a lower NIHSS at discharge (median 4 vs 9, p = 0.013). The day 90 mortality rate (14.3% vs 25.9%, p = 0.11) and favorable outcome (mRS = 0-2) rate (40.8% vs 33.3%, p = 0.39) were similar in patients with a M2 vs M1/ICA occlusion.

Conclusion:
EVT of M2 occlusions is feasible with a similar rate of post-procedural complications and favorable outcome as M1/ICA occlusions. Further trials are needed to demonstrate the efficacy of EVT in comparison to medical management for AIS patients with a M2 occlusion.
Abstract WMP23: Automated Regional Density Measurements on Baseline Non-Contrast CT Predict Final Infarction in Acute Ischemic Stroke Patients
Authors: Kunz Wolfgang G , Forkert Nils D , Tiedt Steffen , Wollenweber Frank A , Kellert Lars , Liebig Thomas , Kemmling André , Reidler Paul
Published: January 2019

Introduction:
Early ischemic changes on non-contrast CT (NCCT) can be visually assessed using the Alberta Stroke Program Early CT Score (ASPECTS). We sought to determine if automated regional density quantification provides additional information on the development of final infarction.

Methods:
We selected 121 patients with middle cerebral artery stroke due to large vessel occlusion out of a consecutive cohort. Densities in ASPECTS regions were quantified as average Hounsfield Unit (HU) values using automated segmentation (Fig. 1). Relative HU (rHU) values were calculated dividing absolute regional densities of ischemic by non-ischemic hemispheres. Final infarction was quantified semi-automatically as total volume and was defined visually per ASPECTS region in a dichotomized fashion. A composite rHU score incorporating values from all ASPECTS regions weighted by regional relevance was calculated. ROC analysis was performed to calculate AUC values. Linear regression analysis was used for multivariable adjustment.

Results:
Median visual ASPECTS on NCCT was 8 (IQR: 6-9). Automated density measurements were feasible in all 121 patients within one minute of post-processing time. rHU values yielded significant regional classification of final infarction in ROC analyses for all ASPECTS regions except M3 and M6. Best classifications were achieved for lentiform nucleus (AUC=0.810, p<0.001), caudate nucleus (AUC=0.777, p<0.001), and insula (AUC=0.764, p<0.001). The composite rHU score was independently associated with final infarction volume (β=-0.353, p<0.001), outperforming visual ASPECTS assessment (β=-0.190, p=0.062) in multivariable regression analysis.

Conclusions:
Automated NCCT density changes identify ASPECTS regions that develop final infarction in stroke patients. The composite rHU score outperformed visual ASPECTS interpretation in the prediction of final infarction volumes and may serve as an observer-independent imaging biomarker.
Abstract WMP32: Endovascular Coiling Recommended for Management of Elderly Patients With Unruptured Cerebral Aneurysm Based on the Nationwide Database in Japan
Authors: Ikawa Fusao , Michihata Nobuaki , Yasunaga Hideo , Kurisu Kaoru
Published: January 2019

Introduction:
Asymptomatic unruptured cerebral aneurysms (UCAs) are frequently discovered at brain check-up in Japan. The Japanese population has a high proportion of elderly individuals, and Japan has the highest life expectancy at birth worldwide. This aging of the population is expected to occur in other countries in the near future. Age is a significant risk factor for UCA rupture in elderly patients. This study aims to clarify the risk factors of age by comparing the outcome at discharge for UCAs between non-elderly (<65 years) and elderly (≥65 years) patients, based on the Diagnosis Procedure Combination database, the national database of in-hospital patients in Japan.

Hypothesis:
Effective treatment for UCA in elderly patients will be required in the future. Endovascular coiling might be a better choice for UCA in the elderly.

Subjects and Methods:
Outcome at discharge was investigated in two patient groups registered in the nationwide database from 2010 through 2015 in Japan. The risk factors were identified by multivariate logistic regression analysis for poor outcome using the Barthel index <90 at discharge in each group. Age, sex, location of UCA, clipping or coiling, medical history, hospital volume, and academic were evaluated as variables. Additionally, propensity score-matched analysis was conducted in both groups to compare the outcomes between clipping and coiling.

Results:
The risk factors for poor outcome at discharge were basilar artery aneurysm (odds ratio [OR], 1.7-2.6; 95% confidence interval [CI], 1.1-4.6), low volume hospital (OR, 2.0-2.5; 95% CI, 1.6-3.7), and diabetes mellitus (OR, 2.0-2.5; 95% CI, 1.6-3.7) in both groups, and age (OR, 1.1; 95% CI, 1.1-1.1) and clipping (OR, 1.7; 95% CI, 1.3-2.1) only in the elderly group. Hyperlipidemia was an adverse risk factor in both groups (OR, 0.6-0.7; 95% CI, 0.4-0.9). No significant difference between clipping and coiling was found in the non-elderly group (p=0.91), but better outcome by coiling was found in the elderly group (p<0.001) by propensity score-matched analysis.

Conclusions:
Treatment of UCA should be performed in high volume hospitals after control of diabetes mellitus. Endovascular coiling is recommended for UCA in elderly patients.
Abstract WMP5: Predictors and Outcome of Eligible Patients for Late Endovascular Treatment: Real Life Analysis From a Comprehensive Stroke Center
Authors: Nannoni Stefania , Strambo Davide , Sirimarco Gaia , Amiguet Michael , Vanacker Peter , Eskandari Ashraf , Dunet Vincent , Saliou Guillaume , Wintermark Max , Michel Patrik
Published: January 2019

Background and Aims:
The DAWN and DEFUSE-3 trials demonstrated the benefit of late endovascular treatment (EVT) in acute ischemic stroke (AIS) patients. We aimed to identify indipendent predictors for late EVT eligibility according to trials and to more liberal criteria. Moreover, we compared the clinical outcome of patients treated with late EVT and fulfilling each set of selection criteria.

Material and Methods:
In the ASTRAL registry (2003-2017), we calculated the proportion of late (6-24 hours) EVT eligibility according to trials and to more liberal criteria (the latter including M2 occlusion, lower NIHSS on admission, and using ASPECTS for core volume estimation). We searched for clinical and radiological variables associated with late EVT eligibility using a multivariate regression. We also analysed functional independence (modified Rankin Scale (mRS) 0-2) at 3 months for patients treated with late EVT.

Results:
Out of 925 late arriving AIS patients with complete data, 2.5% were eligible with DAWN, 5.1% with DEFUSE-3 and 11.1% with liberal criteria. Variables associated with late EVT eligibility are shown in Table 1. Functional independence was achieved in 6/14 (42.9%) of the trial-eligible, and in 11/27 (40.7%) of the liberal-eligible patients treated with EVT. After adjustment for age, NIHSS, vigilance impairment, ASPECTS and acute glucose, DEFUSE-3-like patients showed better outcome than DAWN-like and liberal criteria selected patients (OR 4.45; 95%CI 1.11-17.85).

Conclusion:
Among late arriving AIS patients, only 5% were eligible for late EVT based on trials criteria. Radiological variables were stronger than clinical predictors to identify DAWN and DEFUSE-3 patients. In the small cohort of effectively treated patients, satisfying DEFUSE-3 was associated with the most favourable outcome.
Abstract WMP55: Increased Risk of Acute Ischemic Stroke in Multiple Sclerosis: Analysis of a Large National Cohort
Authors: Ikram Asad , Farooqui Mudassir , Qeadan Fares , Bzydra Piotr , Quadri Syed A , Khan Muhammad A , Ford Corey , Nunez-Gonzalez Joel , Zafar Atif
Published: January 2019

Background:
The advent of mechanical thrombectomy in acute stroke care has reignited interest in the arena of neuro-inflammation and neuro-plasticity to optimize stroke management and further improve outcome. Even though there is an early evidence suggesting increased risk of ischemic stroke (IS) in pro-inflammatory states like lupus, rheumatoid and even multiple sclerosis, cardiovascular risk factor association has yet to be comprehensively studied in Multiple Sclerosis (MS). This is the first ever North American Study focusing on prevalence of ischemic stroke in the largest MS cohort.

Method:
This retrospective study included all patients diagnosed with MS from 2000 to 2016, identified using ICD-9/10 codes. The data were extracted from the Cerner's Health Facts database. From the pool of MS patients, IS was identified and their comorbidities are identified. Multiple logistic regression was used to evaluate the odds of having IS in patients with MS. Statistical analysis performed by the SAS v
ersion
9.4, Cary, NC, USA.

Result:
A total of 83,222 patients with a diagnosis of MS were identified. IS was officially diagnosed in 2,159 (2.59%) and intracerebral hemorrhage (ICH) in 191 (0.22%) patients with MS. Patients with MS had 1.6 times more likelihood of having an IS as compared to non-MS patients (p<0.0001). The study identified the presence of vascular risk factors in the patients with MS. Patients who had MS and had ages between 41-64 (OR 1.75, CI 1.51-2.03), hypertension (OR 4.77, CI 4.201-5.412), Coronary Artery Disease (OR 2.09, CI 1.843-2.380), heart failure (OR 1.38, CI 1.175-1.621), atrial fibrillation (OR 1.61, CI 1.361-1.894), diabetes mellitus (OR 1.58, CI 1.40-1.76), peripheral vascular disease (OR 2.38, CI 1.90-2.98), and smoking (OR 1.29, CI 1.15-1.45) were more likely to have an IS as compared to those who did not have MS and these risk factors.

Conclusion:
This is one of the largest MS cohort studies confirming prior reports of higher incidence of IS in MS population, especially in the 41-64 age group, after adjusting for cardiovascular risk factors. Future prospective epidemiological and molecular studies can open new diagnostic and treatment avenues.
Abstract WMP66: Differences in Diagnostic Evaluation in Women and Men After Acute Ischemic Stroke
Authors: Bruce Samuel S , Merkler Alexander E , Chen Monica L , Omran Setareh S , Navi Babak L , Kamel Hooman
Published: January 2019

Introduction:
Sex differences have been found in stroke risk factors, incidence, treatment, and outcomes. There are conflicting data on whether diagnostic evaluation for stroke may differ between men and women.

Methods:
We performed a retrospective cohort study using inpatient and outpatient claims between 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients who were ≥65 years old and hospitalized with ischemic stroke, defined by validated
ICD-9-CM
diagnosis codes. Medicare providers’ specialty codes, National Provider Identifier numbers, and data from the American Board of Psychiatry and Neurology were used to determine which patients were evaluated by a neurologist or vascular neurologist during their index stroke hospitalization or within 90 days of discharge.
CPT
codes were used to ascertain whether intracranial vessel imaging, cervical vessel imaging, echocardiography, and heart-rhythm monitoring were performed during the same period. Logistic regression was used to determine the association between female sex and the odds of diagnostic testing and specialist evaluation after adjustment for age, race, and number of Charlson comorbidities.

Results:
Of 66,989 patients with ischemic stroke, 58.4% (95% CI, 58.1-58.8%) were female. After adjustment for age, race, and comorbidities, female sex was associated with decreased odds of intracranial vessel imaging (OR, 0.94; 95% CI, 0.91-0.97), cervical vessel imaging (OR, 0.90; 95% CI, 0.87-0.93), heart-rhythm monitoring (OR, 0.92; 95% CI, 0.86-0.98), echocardiography (OR, 0.92; 95% CI, 0.89-0.95), evaluation by a non-vascular neurologist (OR, 0.95; 95% CI, 0.92-0.99), and evaluation by a vascular neurologist (OR, 0.94; 95% CI, 0.90-0.98). Our findings were unchanged in sensitivity analyses excluding patients who died during the index hospitalization or patients discharged to hospice.

Conclusions:
In a nationally representative cohort of Medicare beneficiaries, we found that women with ischemic stroke were less likely to be evaluated by stroke specialists and less likely to undergo standard diagnostic testing compared to men.
Abstract WMP69: Differential Risk Factor Profile in Cryptogenic Stroke Patients May Help Identify High Yield Candidates for Long-term Cardiac Monitoring in Detection of Paroxysmal Atrial Fibrillation
Authors: Xu Jindong , Biby Sharon , Sethi Pramod
Published: January 2019

Introduction:
Paroxysmal afib is the most common cause of cryptogenic strokes. Long-term insertable cardiac monitor (ICM) has been increasingly used for ongoing evaluation of afib in these patients. Due to financial affordability, it is important to identify appropriate candidates for its routine use.

Methods:
We reviewed EMRs of a cohort of cryptogenic stroke patients from February 2014 to May 2017 who received REVEAL LINQ ICMs. All patients met ESUS criteria prior to insertion and were enrolled in remote follow-up. At least one year monitoring was conducted if no afib was recorded. Patient demographics, stroke characteristics and risk factors were compared between patients with and without afib.

Results:
Among total 348 patients enrolled, 99 (28.5%) were found to have afib with median time to afib detection of 128 days. For patients without afib, the median length of follow up was 566 days. Patients with afib were significantly older (mean ± SD, 73.0 ± 9.42 vs. 64.4 ± 11.5, p<0.00001) and their left atrium size (mm) were significantly larger (37.9 ± 7.26 vs. 35.4 ± 5.81, p<0.005) than those patients without afib. Non-afib patients had statistically more frequent association with ongoing smoking or LDL ≥ 120 comparing with afib patients (p<0.05). Although not statistically significant, there was tendency that posterior circulation only strokes occurred less in afib group (p=0.08). However, intra- and extracranial atherosclerosis were comparable between afib and non-afib groups. Within the afib group, afib was detected within 30 days in 25 patients with median time to detection of 14 days. These patients had significant higher rate of intracranial stenosis (p=0.01) comparing with those patients with afib detected beyond 30 days.

Conclusion:
Paroxysmal afib related strokes account for about one-fourth of cryptogenic strokes in our cohort. Long term ICM may benefit more in older patients with enlarged left atrium and lack of risk factors such as smoking and high LDL. It likely has low yield in patients with posterior infarcts only. Noninvasive ambulatory ECG monitoring for 30 days may be considered first in patients with intracranial stenosis.
Abstract WMP80: Inflammation in Aging Increases Ischemic Stroke Burden
Authors: Campbell Robert , Denorme Frederik , Manne Bhanu K , Majersik Jennifer , Weyrich Andrew , Rondina Matthew
Published: January 2019

Rationale:
Acute increases the risk for stroke and adverse outcomes following stroke, such as disability and death. Aging is characterized by increased circulating inflammatory agonists, including interferons (IFNs), and hyperactive platelets. However, whether IFNs generated during aging enhance platelet activation to promote ischemic stroke remains uncertain.

Objective:
We determined whether IFNs regulate platelet activation and ischemic stroke during human and murine aging.

Methods:
Younger (8-12 weeks) or aged (>18 months) male mice were stimulated
in vivo
with IFNα or vehicle control (t=4 days). Mice were then subject to the transient middle cerebral artery occlusion stroke model (t=1 hour followed by reperfusion for 24 hours). Mortality and stroke infarct size were determined. In parallel, we assessed the expression of interferon-sensitive genes (ISGs) and platelet activation from IFN or control treated mice. We also examined platelet activation and ISGs in platelets from younger (age<45) and older (age>65) adults.

Results:
In aged mice, IFNα significantly increased infarct size (56.2±5.5mm
3
vs 27.3 ±3.0 mm
3
, p<0.0001) and mortality (55% vs. 10%, p<0.05) compared to control mice. Consistent with a greater stroke burden, IFNα significantly worsened neurological outcomes.
Ex vivo,
IFNα significantly increased fibrinogen uptake and platelet aggregation. In comparison, IFNα did not alter infarct size or mortality in younger mice. We next dissected the mechanism controlling IFNα-induced platelet aggregation and stroke. We identified that interferon-induced transmembrane proteins (IFITMs, a type of ISGs) were upregulated in platelets from aged mice and older humans (settings where IFNs and platelet activation are increased). IFITMs also increased significantly in platelets following IFNα simulation
in vivo
. Deletion of IFITMs was sufficient to rescue IFNα-induced platelet aggregation and thrombosis-related mortality.

Conclusion:
In aging, IFNα increases platelet aggregation, stroke burden, stroke-related mortality, and neurological deficits. This pathway critically involves platelet IFITMs, which are upregulated in aging and functionally control fibrinogen uptake, platelet aggregation, and thrombosis.
Abstract WMP82: Brain-Derived Microparticles Mediate Cardiac Dysfunction After Stroke
Authors: Chen Zhili , Yan Tao , Yang Shu , Li Wenkui , Hu Haotian , Zacharek Alex , Venkat Poornima , Chopp Michael , Zhang Jianjing , Chen Jieli
Published: January 2019

Background and Purpose:
Brain injury may induce cardiac damage. Microparticles (MPs, size between 0.1-1mm) are involved in intercellular communication and regulate thrombosis and inflammation. In this study, we investigate whether Brain-derived MPs (BDMP) after stroke contribute to stroke induced heart dysfunction.

Method:
1) Human study: Serum GFAP+MP levels measured by Flow cytometry were obtained from acute stroke patients (≤ 3d post stroke) and normal subjects (n=15/group). 2) Animal study: Adult (8-9m) male C57BL/6J mice were subjected to distal middle cerebral artery occlusion (dMCAo) or sham control. BDMP were extracted from ischemic brain 24h after dMCAo by ultracentrifugation. BDMP (1.5х10
8
) were injected (iv) into normal 8-9 m old C57BL/6J mice daily for 3 consecutive days (n=10). PBS was injected as control (n=9). Using Echocardiography, cardiac function was measured 3 and 30 days after injection. 3) In vitro study: Cultured primary cardiomyocytes were treated with: A) control; B-C) BDMP derived from sham or dMCAo mice; D-E) serum-MP derived from sham or dMCAo mice. Immunostaining, PCR, Western blot and LDH measurements were employed.

Result:
1) Human study: Stroke patients exhibited significant increase of GFAP+MP levels in serum compared to normal subjects. 2) Animal-study: Compared with PBS control group, injection of BDMP results in a significant (p<0.01): A) decrease in cardiac function identified by decreasing LVEF (left ventricular ejection fraction), LVSF (LV systolic fraction) at 3 and 30d post injection; B) increases cardiac fibrosis identified by Sirius Red Staining and increases of cardiac thrombosis measured by CD41, as well as increases leukocyte infiltration in the heart. 3) In vitro study: BDMP and serum-MP derived from dMCAo mice significantly induce cardiomyocyte death, and cardiomyocyte inflammatory factors (MCP1, VCAM1, ICAM, TNFα and TLR2) gene expression compared to sham BDMP or sham serum-MP, respectively; BDMP induces significantly increased cardiomyocyte death, and cardiomyocyte inflammatory factor compared with serum-MP.

Conclusion:
BDMP mediate cardiac dysfunction after stroke. BDMP induced cardiac dysfunction may be associated with increased inflammatory response and thrombosis in the heart.