bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP59: Intraoperative Cbv Measurement for the Treatment of Ischemic Stroke
Authors: Yuki Ichiro , Tachi Rintaro , Ikemura Ayako , Ishibashi Toshihiro , Dahmani Chihebeddine , Abe Yukiko , Kan Issei , Kaku Shogo , Nishimura Kengo , Murayama Yuichi
Published: June 2021

Introduction:
Prediction of ischemic core during the thrombectomy procedure can contribute to the treatment strategy. To evaluate if the Cone Beam CT CBV (CBCT-CBV) can predict the image findings of post procedure MRI, retrospective analysis was performed.

Methods:
A total of 14 ischemic stroke cases with major vessel occlusion underwent CBCT-CBV. A 4 French diagnostic catheter, which was placed in the guiding catheter, was positioned at the ascending aorta. Utilizing 6 seconds acquisition (6Sec Dyna PBV Neuro, Siemens Healthcare), 30% diluted contrast was injected with the speed of 6ml/sec. The reconstruction of the images with CBV color mapping was created immediately after the acquisition. The pre and post procedure CBCT-CBV data was compared with the corresponding MRI images and the results were retrospectively analyzed.

Results:
Of the 14 cases who showed major vessel occlusion, 6 underwent both pre and post CBCT-CBV. Location of the occluded vessels were internal carotid artery (ICA) (4 cases), middle cerebral artery (9 cases) and 1 basilar artery. No case showed increased CBV. Five cases showed a significant reduction of regional CBV (mean reduction; 72.65%) at the end of the procedure. All these cases showed DWI high regions in the post procedure MRI matched with the area of CBCT-CBV reduction (100%). Of the 6 cases who underwent both pre and post procedure CBCT-CBV, 3 showed decreased CBV in the pre-procedure CBV. After the recanalization of the occluded vessels, the regional CBV was normalized to the level of contra lateral side in every case.

Conclusions:
Intra-operative CBCT-CBV showed recovery of the reduced CBV after the recanalization in some cases. The area of reduced CBV at the end of procedure was matched with the DWI positive region in the post-procedure MRI (100%). Intra-operative CBCT-CBV may contribute to the prediction of post-operative ischemic core.
Abstract WP60: Evaluation of Tissue Reversibility by Relative Apparent Diffusion Coefficient Value in Acute Ischemic Stroke Patients Treated With Successful Thrombectomy
Authors: Ueda Toshihiro , Takada Tatsuro , Nogoshi Shinji , Takaishi Satoshi , Yoshie Tomohide , Fukano Takayuki
Published: June 2021

Background:
By recent advance of endovascular thrombectomy, we have often experienced acute ischemic patients who have diffusion weighted imaging (DWI) reversal lesions after earlier successful recanalization. We retrospectively investigated the relationship between apparent diffusion coefficient (ADC) thresholds of tissue infarction and time from onset to recanalization in acute ischemic stroke patients.

Methods:
We assessed 24 patients who have occlusion of internal carotid artery (n=11) and the main trunk of middle cerebral artery (n=13) and obtained recanalization of TICI2b (n=12) and TICI3 (n=12) by thrombectomy and performed MRI before and after treatment. Relative ADC (rADC) value were calculated for initial DWI lesions and around hypoperfused regions. We evaluated rADC values in infarcted and non-infarcted area and analyzed the relationship between rADC thresholds of tissue infarction and time.

Results:
The mean time from onset to recanalization was 209 minutes and mean initial NIHSS was 15.4. The mean rADC value was 0.633 in infarcted lesions and 0.905 in non-infarcted area (p<0.001). The thresholds for rADC value for infarction by the area under the curve derived from receiver operating characteristic curve analysis were 0.769 in the area which recanalized under 180 minutes form the onset, 0.792 in that from 180 to 240 minutes, and 0.798 in that over 240 minutes.

Conclusion:
The estimation of rADC value may be useful in predicting the likelihood of DWI lesion reversal. Marked decreasing of rADC value which is under thresholds of infarction indicated irreversible damage of ischemic tissue regardless of early successful recanalization.
Abstract WP63: Infarct Location Predicts Outcome Following Distal Middle Cerebral Artery Occlusion
Authors: Khan Muhib A , Baird Grayson , Goddeau Richard , Silver Brian , Henninger Nils
Published: June 2021

Background:
Although it is generally thought that patients with distal middle cerebral artery (MCA) occlusion have a favorable outcome, it has previously been demonstrated that a substantial minority will have a poor outcome by 90 days. We sought to determine whether the infarct location information encoded in the Alberta Stroke Program Early CT Score (ASPECTS) allows for defining distinct ASPECTS regions that are associated with a poor outcome to improve outcome prediction in in these patients.

Methods:
We retrospectively analyzed patients with isolated acute distal MCA occlusion admitted to a single academic center between January 2010 to August 2012. Infarct regions were defined according to ASPECTS system on the initial head CT. Discriminant function analysis was used to define specific ASPECTS regions that are predictive of the 90 day functional outcome. In addition, logistic regression was used to model the relationship between each individual ASPECT region with poor outcome; for evaluation and comparison, odds ratios, c-statistics, and Akaike information criterion values were estimated for each region.

Results:
90 patients with isolated distal MCA were included in the final analysis. ASPECTS score ≤ 6 predicted poor outcome in this cohort (sensitivity=0.591, specificity=0.838, p<0.001). Using multiple statistic approaches we found that infarction in ASPECTS regions M3 and M6 were strongly associated with poor functional status (mRS 3-6) by 90 days.

Conclusion:
ASPECTS regions M3 and M6 are key predictors of functional outcome following isolated distal MCA infarction. These findings will be helpful in stratifying outcomes if validated in future studies.
Abstract WP66: Unexpected Conformational Change of Platelet Glycoprotein Ib (GPIb) Receptor After rt-PA Treatment of Large Vessel Ischemic Stroke
Authors: Da Qi , Mandava Pitchaiah , Cruz Miguel , Thiagarajan Perumal , Kent Thomas A
Published: June 2021

Introduction:
Many stroke patients do not fully respond to intravenous rt-PA, possibly due to factors that increase clot resistance or impede reperfusion. GPIb receptors on the platelet surface initiate vessel occlusion through an interaction with subendothelium-bound von Willebrand Factor and the interaction transduces signals resulting in further activation. An increase in GPIb availability may result in macro or micro-vascular thrombosis. We report the effect of rt-PA on a potential compensatory conformational response of platelet GPIb.

Methods:
5 subjects with large artery stroke and treated with rt-PA within 4.5 hours of onset were enrolled after consent. Blood was obtained immediately before and 1.3 hours post rt-PA bolus. Blood was incubated with 3 monoclonal antibodies (mABs: AN51, 6D1 and SZ2) and control antibody. AN51 and 6D1 are conformation sensitive and SZ2 is relatively less conformation sensitive. Flow cytometry was performed to assess fluorescent intensity of platelets pre and post-treatment and corrected for non-specific staining with control IgG. Blood from healthy donors subjected to appropriate concentrations of rt-PA in vitro was tested for conformational changes with AN51 and 6D1.

Results:
Compared to pre-treatment, 4 of 5 patients showed increased GPIb or binding with AN51 and 6D1 post treatment, with an overall median percentage increase with AN51 of 40.6% and 60.3% with 6D1. SZ2 showed a smaller increase (30.7%). The 1 subject who showed no change had the only hemorrhagic transformation. Blood from healthy donors showed an increase of 21.4% with AN51 and 41.3% with 6D1 after rt-PA.

Conclusion:
These results indicate for the first time rt-PA induced conformation changes on platelet GPIb in acute ischemic stroke in vivo despite that GPIb is not the direct target. These changes were also seen with rt-PA in vitro. It is possible that up-regulation of GPIb receptors plays a protective role in preventing hemorrhages but also may mediate increased propensity for clot resistance or downstream thrombosis. If confirmed in a larger ongoing sample, measuring GPIb binding may provide a rational approach to post-rt-PA antiplatelet therapy and identify a risk for hemorrhagic transformation.
Abstract WP69: Reversible Aptamer Inhibition of Von Willebrand Factor is a Potent Thrombolytic and Ameliorates Stroke Burden Following Vascular Injury Compared to Recombinant Tissue Plasminogen Activator
Authors: Dornbos David L , Harris Hallie , Gnyawali Surya , Wheeler Debra G , Huttinger Allyson , Venetos Nicholas , Talentino Spencer , Vaccaro Hope , Musgrave Nicholas , Jones Cheyenne , Amaya Pedro , Rink Cameron , Zweier Jay L , Sen Chandan K , Nimjee Shahid M
Published: June 2021

Introduction:
While recombinant tissue plasminogen activator (rTPA) is the mainstay of ischemic stroke treatment, few patients are eligible for treatment, and recanalization is only seen in 25-50%. Von Willebrand Factor (VWF) inhibition may play a role in thrombolysis.

Hypothesis:
VWF inhibition with an RNA aptamer lyses arterial thrombus and decreases ischemic injury. Furthermore, aptamer reversal with an antidote oligonucleotide ameliorates intracranial hemorrhage (ICH).

Methods:
Adult wild-type (C57BL/6J) mice were anesthetized, and the right carotid artery was exposed. Baseline carotid flow was obtained using a Doppler flow probe, and thrombotic occlusion was induced with a ferric chloride patch. After clot stabilization, mice were administered vehicle (platelet binding buffer, n=11), no infusion (n=8), rTPA (n=5) or VWF aptamer (n=5). Carotid flow was monitored for an additional 100 minutes. In a second cohort of mice, a 6-0 nylon suture was advanced within the carotid artery to generate vascular injury and ICH. Mice were given vehicle (n=16), rTPA (n=11), VWF aptamer (n=9) or aptamer/antidote (n=8). An MRI was obtained after 90 minutes to assess stroke and ICH volumes.

Results:
VWF aptamer successfully restored carotid blood flow 45 minutes following carotid occlusion (Figure 1) compared to controls (p<0.01*) and rTPA (p<0.05
+
). Stroke volume was significantly decreased in mice treated with VWF aptamer (23.03 ± 6.81 mm
3
) and aptamer/antidote (12.48 ± 5.68 mm
3
) compared to vehicle (45.25 ± 4.14 mm
3
, p<0.01). ICH volumes in mice treated with rTPA (2.64 ± 0.84 mm
3
) were trending higher than vehicle (1.51 ± 0.17 mm
3
), VWF aptamer (1.92 ± 0.22 mm
3
) or aptamer/antidote (1.31 ± 0.35 mm
3
).

Conclusions:
Aptamer inhibition of VWF is a potent thrombolytic agent with greater efficacy compared to rTPA. VWF inhibition appears safe with a trend toward lower ICH volumes in animals treated with aptamer and aptamer/antidote compared to rTPA.
Abstract WP71: Intravenous Thrombolysis in Stroke-mimics: Is There a Relationship With Door-to-needle Time?
Authors: Campos-Costa Elisa , Labandeira-Guerra Carmen , Martínez-Reglero Cristina , Boned Sandra , Muchada Maria , Rodríguez-Luna David , Rodríguez-Villatoro Noelia , Juega Jesus , Pagola Jorge , Molina Carlos A , Ribó Marc , Rubiera Marta
Published: June 2021

Introduction:
Several non-vascular conditions may mimic the sudden neurological deficits of stroke (stroke mimics, SM). In Stroke Code, time to treatment is crucial, but the efforts to increase the benefits of iv-tPA may lead to inadvertent treatment of SM. We aim to determine the relationship between door-to-needle (DTN) time and SM treatment.

Methods:
Retrospective analysis of all acute stroke patients treated with iv-tPA included in an institutional prospective database. SM were identified during follow-up and their clinical characteristics compared with the confirmed stroke patients in the same time-period.

Results:
During a 3-year period, 332 thrombolysed patients were included. Twenty-two were SM (6.6%, 95%CI:4.0%-9.3%), with median age of 58 years (range 35-87), 54.5% were men, median NIHSS=10 (range 3-30). Sudden (81.8%) neurological deficits were motor in 11 patients (52.2%), altered speech in 10 (47.6%) and sensitive in 7 (33.3%). Baseline clinical characteristics (including age, sex, vascular risk factors and initial NIHSS) were similar between stroke and SM groups. Multimodal imaging was used for treatment decision in 95.5% of SM (CT-perfusion 10 patients, CT-angiography 9, MRI 1 and only 1 patient received just non-contrast CT) vs 74.1% of confirmed strokes (p=0.014). Four SM patients presented with neuroimaging abnormalities. DTN of SM was similar to those of strokes (35.5 VS. 40minutes, p=0.6). Despite a progressive decrease in median DTN time (year 1: 47min vs year 3: 36min; p=0.02) the rate of SM treated with tPA did not increase (year 1: 5.4% vs 9% in year 3; p=0.1). No intracranial haemorrhage or other complications were recorded in any SM patient. At discharge, 86.4% of SM presented a modified Rankin Scale 0-1. The most frequent final diagnosis were: migraine (31.8%), functional symptoms (27.3%) and seizures (27.3%).

Conclusions:
Despite multimodal neuroimaging, stat differentiation between SM and stroke is still difficult. Reduction of DTN times may not necessarily increase the number of SM thrombolysed. Nevertheless, iv-tPA revealed to be safe in SM and should not be delayed in case of doubt.
Abstract WP72: Early Experience on Intravenous Tissue Plasminogen Activator Delivery in Mobile Stroke Unit Patients with Stroke Mimics
Authors: Sheikhi Lila E , Winners Stacey , George Pravin , Russman Andrew , Khawaja Zeshaun , Uchino Ken , Hussain Muhammad S ,   On behalf of the Cleveland Pre-Hosp Acute Stroke Treatment (PHAST) Study Group
Published: June 2021

Background:
A mobile stroke unit (MSU) allows for early delivery for intravenous tissue plasminogen activator (IV-tPA). A proportion of IV-tPA treated patients may turn out to be stroke mimics. We evaluated the rate and complications seen in stroke mimics treated with tPA from our early experience on MSU.

Methods:
Retrospective review of patients treated with IV-tPA on the MSU from 2014 to 2016. Charts were reviewed for confirmed strokes by imaging (MRI or CT) and hemorrhagic transformation. Stroke mimics were defined as those without imaging evidence of infarction and a final diagnosis which was not suspected to be stroke.

Results:
Among 62 patients treated with IV-tPA, 14 (28.6%) had a final diagnosis consistent with a stroke mimics. The majority of these occurred in the first year of the MSU program. Most common mimics included conversion disorder (n=5) and seizures (n=5). While the last known well to IV-tPA times were similar, the MSU door-to-needle time was significantly longer in stroke mimics (38 vs 31 minutes, p = 0.03). No intracerebral hemorrhages or other IV-tPA related complications were identified in the stroke mimics group.

Conclusions:
In our early experience with MSU, treatment of stroke mimics occurred without IV-tPA related complications. This does not appear to be due to rushed decision making.
Abstract WP74: Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Taking Warfarin with Subtherapeutic INR
Authors: Memon Aurangzeb , Lail Navdeep , Kamal Haris , Crumlish Annemarie , Ching Marilou , Sawyer Robert N , Mowla Ashkan
Published: June 2021

Introduction:
AHA/ASA guidelines allow use of IV rtPA in warfarin-treated acute ischemic stroke (AIS) patients with INR ≤1.7. Concerns remain regarding safety of IV rtPA, as value of 1.7 was not determined through randomized trials, and available data is controversial.

Objectives:
To evaluate symptomatic intracranial hemorrhage (sICH) rate and outcome of IV rtPA treated AIS patients taking warfarin with INR ≤ 1.7, and compare with non-warfarin patients. Also, to evaluate rate of sICH and outcome in different INR ranges in warfarin-treated AIS patients who received IV rtPA.

Methods:
Retrospective chart review was performed on patients who received IV rtPA for AIS from the beginning of January 200 till the end of August 2015 (n=834), with 55 patients (6.5%) identified to be on Warfarin prior to AIS. One of these patients was excluded because of INR being greater than 1.7. Due to differences in sample size (54 vs 779), Warfarin group was matched in case-control manner with 54 non-warfarin patients with similar sICH risk factors (age, admission NIHSS, history of diabetes, history of atrial fibrillation), eliminating need to adjust for covariates. Good outcome was defined as mRS of 0-2 on discharge, and sICH was defined as an increase in NIHSS ≥4. Frequencies of good outcome and sICH were calculated for each group and compared. Warfarin group was also dichotomized based on INR (1-1.3 vs 1.31-1.7), and safety and outcome measures of the two groups were compared.

Results:
In the Warfarin group, 2 patients (3.7 %) developed sICH post IV rtPA . Fifteen patients in this group (27.8%) had good outcome on discharge. After case-control matching, no significant difference was found in the frequency of patients with good outcome on discharge or occurrence of sICH between warfarin and non-warfarin groups (P=0.270 and P=0.874 respectively). Also, there were no between group differences in frequency of patients with good outcome and rate of sICH between subjects on Warfarin with an INR 1.31-1.7 ( 0 % with sICH; 26.7% with good outcome) and those with INR < 1.3 (5.1% with sICH ; 28.2 % with good outcome) (p=0.910 and p=0. 371 respectively)

Conclusion:
Our results suggest that IV rtPA does not increase the risk of sICH in Warfarin treated patients with INR≤1.7.
Abstract WP79: Demographic Comparison of Intracranial and Abdominal Aortic Aneurysm Patients
Authors: Rosenbaum Blake L , Chiota-McCollum Nicole A , McKinley Claire , Krupa Julia K , Meschia James F , Barrett Kevin M , Southerland Andrew M , Worrall Bradford B
Published: June 2021

Background:
The risk for intracranial (IA) and abdominal aortic aneurysms (AAA) is partially heritable, with evidence mounting in favor of shared genetic risk for both.

Methods:
The Brain and Aortic Aneurysm Study (BAAS, NCT#17341) at University of Virginia seeks to determine the coprevalence of IA and AAA recruiting patients presenting with an aneurysm at one site and screening for aneurysm at the other. Participants undergo genetic screening and an interview where clinical, demographic, and radiographic data are collected. Recruitment and screening are ongoing, so preliminary demographic data regarding between group differences (IA vs. AAA) are presented. All clinical and demographic data were collected and recorded in REDCap and exported to Excel. We compared a total of 256 participants (IA=164, AAA=92) for demographic factors: age, sex, smoking and past medical history.

Results:
The AAA cohort was older (70.98 vs. 58.51, p<.001) and more male (79.34% vs. 23.78% p<.001). The AAA cohort had a higher proportion with diabetes mellitus (28.26% vs. 15.24%, p=.012), with hyperlipidemia (67.39% vs. 44.51%, p<.001) and higher smoking pack years (44.07 vs. 17.85, p<.001). The two groups did not differ in proportion with hypertension, coronary artery disease, or peripheral vascular disease (all p>.05).

Conclusions:
These data suggest that there may be subtle differences in the clinical profile of patients presenting with IA and AAA, especially when considering known aneurysmal risk factors like hypertension, diabetes, and smoking history. Further analyses will consider whether these factors modulate the coprevalence of the two types of aneurysms.
Abstract WP8: Initial Clinical Experience with the Double Aspiration Modification of the ADAPT Technique
Authors: Chastain Logan , Burke Robert , Muehle Casey , Siddiqui Fazeel , Greer William E , Elias Augusto
Published: June 2021

Background:
The improvement of revascularization techniques has decreased recanalization times, increased rates, and improved patient outcomes. We report our initial results using a double aspiration modification to the direct aspiration first pass technique as the primary method for vessel recanalization.

Methods:
A retrospective evaluation of a prospectively captured group of 15 patients at one institution was performed on patients where the double aspiration modification of the ADAPT technique was used.

Results:
The double aspiration technique by itself was adequate for recanalization of TICI 2b/3 in 13 of 14 (93%) cases without any instance of downstream emboli needing additional aspiration. Two cases needed the addition of a stent retriever to achieve recanalization. Average time from groin puncture to at least TICI 2b was 39 minutes, and all cases but one was successfully revascularized. TICI 3 recanalization was achieved 57% of the time. The average National Institutes of Health Stroke Scale (NIHSS) on admission was 14.3 and this improved to an average NIHSS of 7.25 prior to discharge. The modified Rankin Score at 90 days showed 7 of 14 (50%) with a score of one. There were no procedural complications.

Discussion:
As previous studies have shown, aspiration technique is just as important as the aspiration device. This initial experience shows that the double-aspiration modification of the ADAPT technique is an effective method for mechanical thrombectomy in acute ischemic stroke. Utilizing the double-aspiration modification may decrease the incidence of downstream embolization, but further studies are needed to confirm this finding.
Abstract WP80: Efficacy of Coiling Versus Clipping for Posterior Communicating Artery Aneurysms Causing Oculomotor Nerve Palsy: A Systematic Review and Meta-analysis
Authors: Siqi Ou , Feng Liang , Fanying Li , Yibing Yang , Tiewei Qi
Published: June 2021

Objective:
To compare the advantages in respect of recovery from oculomotor nerve paralysis(ONP) between endovascular coiling and surgical clipping in the treatment of cases with posterior communicating artery (PComA) aneurysms in China.

Methods:
By retrieving PubMed, Cochrane Library, Embase, Chinese Biomedicine Database(CMB), Chinese National Knowledge Infrastructure(CNKI) and other domestic literature database, we collect relevant studies of cases in China from 2004 to 2015. Using Review Manager (RevMan) version 5.0 software, we perform a systematic review of literature and conduct meta-analysis.

Result:
The meta-analysis included 12 related studies involving 712 Chinese patients with ONP secondary to PComA aneurysms, of whom 302(42.4%) were treated by endovascular coiling while 410(57.6%) received surgical clipping. Surgical clipping (298 of 410 patients, or 72.7%) resulted in greater complete recovery from ONP compared with endovascular coiling (151 of 302 patients, or 50.0%), in correspond to overall pooled odds ratio (OR) of 0.39 [confidence interval (CI) =0.19-0.83, P = 0.01]. The subgroup analysis reveal a significant benefit of surgical clipping over endovascular coiling in cases with preoperative ruptured aneurysms(P=0.01)or complete initial ONP(P=0.002).

Conclusion:
Better resolution of ONP with PComA aneurysms is more commonly associated with clipping than coiling, which could be especially true in the patients with preoperative ruptured aneurysms or complete initial ONP. A randomized trial including more cases is expected to elaborate this effect.
Abstract WP88: Relationship Between Aneurysm Size and Distal Cerebral Hemodynamics
Authors: Hussein Ahmed E , Brunozzi Denise , Shakur Sophia F , Charbel Fady T , Alaraj Ali
Published: June 2021

Introduction:
The impact of aneurysms on distal cerebral hemodynamics is unknown. Here we examine the relationship between aneurysm size and distal hemodynamics prior to treatment.

Methods:
Patients seen at our institution between 2006-2015 with aneurysms within the cavernous or supraclinoid ICA segment (proximal to ICA terminus) were retrospectively reviewed. Only un-ruptured proximal anterior circulation aneurysms were included, patients with contralateral aneurysms were excluded. Patients were included if they had flow volume rate and flow velocities measured prior to any treatment using Quantitative MRA. Pulsatility index (PI) = [(systolic - diastolic flow velocity)/mean flow velocity] was calculated for ipsilateral and contralateral MCA and ICA. Hemodynamic parameters were analyzed with respect to aneurysm size.

Results:
42 patients were included. Mean aneurysm size was 13.5 mm (range 2-40mm). There was significant correlation (Pearson’s) between aneurysm size and ipsilateral MCA PI (
P
=0.006; r=0.441), MCA
ipsilateral
/ICA
ipsilateral
PI ratio (
P
=0.003; r=0.57), and MCA
ipsilateral
/MCA
contralateral
PI ratio (
P
=0.008; r=0.43).

Conclusions:
Larger aneurysm size is significantly associated with higher ipsilateral MCA PI, demonstrating that aneurysms change distal cerebral hemodynamics. Aneurysm treatment may thus acutely change those altered hemodynamics.
Abstract WP90: The Role of Haemodynamics in a Bifurcation Vessel Narrowing or Occlusion After Aneurysm Treatment with Flow Diverter Stents
Authors: Narata Ana Paula , Silva Fernando , Larrabide Ignacio , Perrault Cecile , Sennoga Charles , Marzo Alberto
Published: June 2021

Background and Purpose:
Treatment of intracranial aneurysms at bifurcations with flow-diverter stents (FDS) can lead to occlusion/narrowing of the distal vessels. This study investigated the role played by haemodynamics within different bifurcation types treated with FDS.

Materials and Methods:
Radiological images, demographic and outcome data were acquired for 25 bifurcating aneurysm treated with FDS. Statistical analysis was used to correlate the event of occlusion/narrowing with anatomical data. Computational Fluid Dynamics (CFD) study was performed on idealized and patient-specific anatomies to identify possible cause-effect mechanisms mediated by haemodynamics.

Results:
Statistical analysis identified marked correlation between asymmetric bifurcation and occlusion/narrowing (diameters ratio=DR=1 symmetric, <1 asymmetric). CFD predictions in both idealized and patient-specific anatomies showed that wall shear stress (WSS) in the jailed vessel is mostly affected when FDS are deployed in non-symmetric bifurcations (DR<0.65), and least affected when deployed in symmetric anatomies (DR = 1.00).

Conclusion:
Analysis of the anatomical data showed statistically significant correlations between occlusion/narrowing and bifurcation asymmetry characterized by DR<0.7. Similarly, CFD results showed that FDS have the highest impact on haemodynamics when deployed in bifurcations with higher degrees of anatomical asymmetry (DR<0.65) with strong changes induced on the WSS fields. This suggests a higher risk associated to FDS-treatment of asymmetric bifurcation together with a possible FDS-induced pathway leading to occlusion/narrowing of arteries and mediated by haemodynamics and endothelial response.
Abstract WP95: Splenectomy Protects Aged Mice From Cerebral Injury in the Experimental Stroke Model
Authors: Chauhan Anjali , Roy-O’Reilly Meaghan , Mamun Abdullah , Harris Nia , Bravo-Alegria Javiera , McCullough Louise
Published: June 2021

Introduction:
Aging is a non-modifiable risk factor for stroke. Although aged animals tend to have smaller infarcts they have worse functional recovery after stroke, suggesting difference in mechanisms between young and aged. Splenectomy reduces infarct in animal models, but how the spleen contributes to brain injury in aged mice has not been as well studied.

Hypothesis:
We hypothesized that peripheral inflammation increases over the lifespan. We predicted that the detrimental effects of the spleen would be reversed by splenectomy in aged mice.

Methods:
Young and aged male mice were splenectomized (n= 8-9), 2 weeks prior to induction of 1 hour of middle cerebral artery occlusion. Ninety-six hours after reperfusion, behavioral and infarct area was assessed. In a separate cohort, peripheral and central immune cells were quantified by flow cytometry.

Results:
After stroke, there was 13.3, 17.7, 25.9 and 5.88% mortality in spleen intact young, splenecyomized young, spleen intact aged and splenctomized aged mice respectively. Splenectomy led to improved behavioral deficits in aged mice as seen by lower neurological deficits scores,(1.63 ± 0.26 Vs 2.57 ± 0.20) and reduction in number of right turns in the corner test. There was significant reduction in infarct size in the splenectomized aged mice (p<0.05) as compared to spleen-intact mice. Splenectomy in aged mice lead to reduction in the frequency of CD3CD44+ T cells. Additionally, there was significant decrease in TNF-α, IL-6, IL-4, IL-12MIP-1b and RANTES levels in the aged splenectomized aged mice as compared to spleen-intact aged mice (p<0.05). In the brain, the frequency of CD45hiCD11b+ cells was reduced in the splenectomized MCAo aged as compared to spleen-intact stroke mice (p<0.05).

Conclusions:
Splenectomy reduced the peripheral activation of T cells in the aged mice. Also less peripheral leukocyte infiltration was observed, which mirrored improved functional recovery and reduced infarct damage in splenectomized aged mice. Hence, this study provides new information regarding age specific peripheral immune responses and interaction with the brain after experimental stroke highlighting a need for the incorporation of aged mice in the basic stroke research. Funding: 16POST27490032
Abstract WP96: The Histone Deacetylase Inhibitor, Sodium Butyrate, Exhibits Biphasic Neuroprotective Mechanisms in the Acute Phase of Ischemic Stroke in Middle-Aged Female Rats
Authors: Park Min Jung , Sohrabji Farida
Published: June 2021

Introduction:
Sodium butyrate (NaB) is a histone deacetylase (HDAC) inhibitor exhibiting anti-inflammatory and neuroprotective effects in a rat ischemic model of a myocardial ischemia as well as stroke. Although clinical evidence shows that older women are at higher risk for stroke occurrence and greater stroke severity, no studies have evaluated the effectiveness of NaB either in females or in older animals.

Methods:
To determine the effects of NaB on stroke in older females, acyclic middle-aged Sprague-Dawley female rats (10-12 months old, constant diestrus) were subject to middle cerebral artery occlusion (MCAo) by intracerebral injection of recombinant endothelin-1. Rats were treated with NaB (300 mg/kg, i.p.) at 6h and 30h following ET-1 injection. Animals were tested for sensory motor performance pre and post stroke. Subsequently, rats were sacrificed at the early (2d) or late (5d) acute phase after MCAo. Serum and tissue samples were collected for biochemical analyses.

Results:
NaB treatment reduced infarct volume and ameliorated stroke-induced sensory motor impairment in middle-aged female rats post MCAo. At the early acute phase, NaB treatment decreased brain lipid peroxides, and reduced serum levels of GFAP, a marker of blood brain barrier permeability. NaB also reduced expression of the inflammatory cytokine IL-1beta in circulation and IL-18 in the ischemic hemisphere. At the late acute phase, NaB treatment further suppressed MCAo-induced increase of IL-1beta, IL-17A, and IL-18 in brain lysates (cortex and striatum) from the ischemic hemisphere, and decreased ischemia-induced upregulation of IL-1beta and IL-18 in circulation, indicating a potent anti-inflammatory effect of the HDAC inhibitor. Moreover, NaB treatment also increased expression of IGF-1, a known neuroprotectant, in peripheral tissues including serum, liver, and spleen.

Conclusions:
These data provide the first evidence that delayed (> 6h) NaB treatment post-stroke is neuroprotective in older female rats. Importantly, these data also show that in addition to its well-known anti-inflammatory actions, NaB may exert a biphasic effect after stroke, operating initially to reduce oxidative stress in the brain, and later, elevating IGF-1 expression in peripheral tissues.
Abstract WP99: Neuroprotective Therapy for Ischemia-Reperfusion Injury by Hemoglobin-albumin-cluster(Hemoact
Tm
)
Authors: Gekka Masayuki , Abumiya Takeo , Komatsu Teruyuki , Funaki Ryousuke , Kurisu Kota , Nakayama Naoki , Kazumata Ken , Shichinohe Hideo , Houkin Kiyohiro
Published: June 2021

Background:
A hemoglobin-albumin cluster designated as “HemoAct” was developed as a red blood cell substitute. It is composed of one core hemoglobin center wrapped covalently by three albumin shells. Since its particle size with a diameter of 10 nm is far smaller than red blood cell, it is expected to maintain good perfusion in the cerebral microvessels, leading to neuroprotective effects on ischemia-reperfusion (I/R) injury.

Purpose:
We aim to examine whether HemoAct have neuroprotective effects in rat transient middle cerebral artery occlusion (tMCAO) model, without toxic effects of hemoglobin, by administering it though the recanalized artery just before the onset of reperfusion.

Subjects and Methods:
Male Sprague-Dawley rats were subjected to 2-hour tMCAO by suture occlusion and then divided into four groups with respective treatments: (1) control group; no infusion, (2) vehicle group; infusion of PBS as the solvent (3) 0.5х HemoAct group; infusion of one-half diluted HemoAct (4) HemoAct group; infusion of undiluted HemoAct. Physical and neurological states, infarct and edema volumes, reactive oxygen species (ROS) and protease immunoblot levels were compared between the four groups after 24 hours of reperfusion. Microvascular hemoglobin perfusion and morphological states were compared between the control and HemoAct groups with immunohistochemical technique.

Results:
No significant changes were observed in blood pressure, pH, and blood gas after HemoAct infusion. Neurological symptoms were significantly less severe in the HemoAct group than in the other groups. Infarct and edema volumes were significantly smaller in the 0.5х HemoAct group (27.1%/15.2%) and the HemoAct group (20.2%/14.1%) than in the control group (55.2%/26.4%) and the vehicle group (53.2%/27.1%). ROS (4-HNE) and protease (MMP-9) immunoblot levels were significantly reduced in HemoAct group compared with the control and vehicle groups. Microvascular hemoglobin perfusion was more and microvascular narrowing changes was less in the HemoAct group than in the control group.

Conclusion:
HemoAct exhibited strong neuroprotective effects on I/R injury without toxic effects of hemoglobin. Superior microvascular perfusion of HemoAct may be a possible neuroprotective mechanism.
Abstract 103: Intravenous Thrombolysis for In-Hospital Ischemic Stroke in the Endovascular Era: Findings From the National Get With the Guidelines-Stroke Registry
Authors: Akbik Feras , Xu Haolin , Xian Ying , Shah Shreyansh , Smith Eric E , Bhatt Deepak L , Matsouaka Roland A , Fonarow Greg C , Schwamm Lee H
Published: June 2021

Introduction:
A significant proportion of acute ischemic strokes occur while patients are hospitalized for other reasons. Limited data exist on the utilization of intravenous alteplase (IV tPA) for in-hospital stroke, particularly in the endovascular era. We compared temporal trends of IV tPA use, patient characteristics, process measures of quality, and outcomes for in-hospital versus community onset strokes in a national registry.

Methods:
We performed a retrospective cohort study of Get With The Guidelines-Stroke (GTWG-Stroke) from January 2008 to June 2018 from 2,333 participating sites that included 2,428,178 patients with acute ischemic stroke. In-hospital onset was reported in 67,493 patients. We examined the association between stroke onset location, patient characteristics, comorbidities, treatment with IV tPA and unadjusted and adjusted functional outcomes (Table, standardized differences >10% for significance).

Results:
Of 67,493 patients with in-hospital onset stroke, 11,123 received IV tPA. The rate of IV tPA administration steadily increased, from 9.5% in 2008 to 20.7% in 2017 (p<0.001). Compared with patients with community-onset strokes who were treated with IV tPA, patients with in-hospital onset stroke had longer times to cranial imaging and administration of IV tPA. Patients with in-hospital onset stroke were less likely to be treated within 60 minutes of recognition, and at discharge, ambulate independently or go directly home. They were more likely to die or be discharged to hospice after adjusting for patient and hospital characteristics.

Conclusions:
In this national cohort, in-hospital onset strokes are increasingly treated with intravenous tPA in a period that spans the endovascular era. Compared with community-onset stroke, patients with in-hospital onset stroke had longer intervals to thrombolysis and worse outcomes. These data highlight opportunities to improve inpatient systems of stroke care further.
Abstract 109: Depletion of Microglia Does Not Improve Functional Outcomes in Aged Mice After Transient Focal Ischemia
Authors: Marino Lee Shirley , Hudobenko Jacob , Lee Juneyoung , McCullough Louise , Chauhan Anjali
Published: June 2021

Introduction:
With aging, microglia acquire a dysfunctional phenotype characterized by dystrophic morphology, impaired phagocytosis, reduced motility, and an exaggerated response to injury. Microglia become pathologically activated with aging and play a detrimental role in age-associated cognitive decline and neurodegenerative diseases. Older mice exhibit a differential response to stroke and have worse outcomes despite smaller infarcts compared to young mice. Microglia from aged mice produce higher levels of reactive oxidative species and have an exaggerated inflammatory response after ischemic stroke.

Hypothesis:
We hypothesized that ablation of microglia would reduce the exaggerated neuroinflammatory responses in aged mice and loss of microglia would improve early recovery after ischemic stroke. Aged (18-19 months) male mice were fed a control chow diet (CD) or PLX5622 chow diet (PLXD) for 21 days. On day 22, 60-minute middle cerebral artery occlusion (MCAo) or sham surgery was performed. Twenty-four hours after MCAo, neurological deficit scores (NDS) and immunohistochemistry assessments, as well as flow cytometry, were performed.

Results:
There was a significant reduction in Iba1
+
cells in striatum and cortex of the aged mice with PLX treatment: day 7 (p<0.05), day 14 (p<0.001), and day 21 (p<0.001) vs day 0. Twenty-four hours after MCAo, the NDS were not different between CD (3.0±0.18) and PLXD (2.92±0.21). However, an increase in infarct size was seen in the aged PLXD group compared to the aged CD group (p<0.05). After MCAo, there was an increase in infiltrating monocytes and neutrophils in both diet groups compared to their respective shams (p<0.05). However, an increase in infiltrating monocytes was observed in the PLXD MCAo vs. CD MCAo (p<0.0001) reflecting a differential monocyte response in animals without microglia. Additionally, a decrease in NeuN immunoreactivity was seen in the PLXD MCAo group compared to PLXD sham (p<0.01). GFAP
+
cells increased in PLXD sham group as compared to CD sham (p<0.05).

Conclusions:
Our results suggest that microglia are essential immune cells that surprisingly limit immune cell infiltration, decrease neuronal degeneration, and reduce neuroinflammation after ischemic stroke in aged mice.
Abstract 112: Genetic Deletion of Endothelial microRNA-15a/16-1 Promotes Cerebral Angiogenesis and Neurological Recovery in Ischemic Stroke Through Src Signaling Pathway
Authors: Sun Ping , Ma Feifei , Zhou Chao , Stetler R. Anne , Chen Jun , Yin Ke-Jie
Published: June 2021

Introduction:
Cerebral angiogenesis is tightly controlled by certain microRNAs (miRs), such as the miR-15a/16-1 cluster, among others. Recently, we demonstrated that endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis and improves long-term neurological recovery by increasing protein levels of VEGFA, FGF2, and their receptors VEGFR2 and FGFR1. Here, we further investigated the downstream signaling pathways of these pro-angiogenic factors by using a potent Src family inhibitor, saracatinib (AZD0530), in endothelial cell-selective miR-15a/16-1 conditional knockout (EC-miR-15a/16-1 cKO) mice after ischemic stroke.

Hypothesis:
Pharmacological inhibition of Src signaling cascade using AZD0530 diminishes enhanced post-stroke angiogenesis and long-term neurological recovery induced by the genetic deletion of miR-15a/16-1 in the endothelium.

Methods:
EC-miR-15a/16-1 cKO and WT littermate controls were subjected to 1h MCAO and 28d reperfusion. AZD0530 (20 mg/kg) was administered daily to both genotypes at 3-21d after MCAO by oral gavage. Cognitive outcomes were determined by Morris water maze tests. Brain atrophy was measured by MAP2 immunostaining. Cerebral blood flow (CBF) was monitored by laser speckle imaging. Brain capillary density and functional vessels were examined by CD31/BrdU and tomato lectin/BrdU double-immunostaining, respectively. Src signaling pathway-related molecules were analyzed by western blotting.

Results:
Treatment with AZD0530 exacerbates cognitive impairments and brain atrophy in EC-miR-15a/16-1 cKO mice following MCAO. AZD0530 also attenuates the long-term CBF recovery, correlated with inhibiting the generation of newly formed microvessels and functional vessels in the peri-infarct brain regions in EC-miR-15a/16-1 cKO mice after cerebral ischemia. Moreover, EC-targeted deletion of miR-15a/16-1 upregulates the Src signaling pathway, while AZD0530 blocks the Src signaling pathway by downregulating p-Src and its downstream mediators (p-Stat3, p-Akt, p-FAK, p-p38 MAPK) in ischemic brains.

Conclusions:
Endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis and improves long-term neurological recovery via Src signaling pathway.
Abstract 116: Predicting Symptomatic Intracranial Hemorrhage After Mechanical Thrombectomy: The TAG Score
Authors: Montalvo Mayra , Mitry Eva , Chang Andrew , Dakay Katarina , Azher Idrees , Kaushal Ashutosh , Mistry Akshitkumar , Chiatle Rohan , Cutting Shawna , Burton Tina , Mac Grory Brian , Reznik Michael , Mahta Ali , Thompson Bradford , Ishida Koto , Frontera Jennifer , Riina Howard , Gordon David , Turkel Parrella David , Scher Erica , Farkas Jeffrey , McTaggart Ryan , Khatri Pooja , Furie Karen , Jayaraman Mahesh , Yaghi Shadi
Published: June 2021

Background:
There is limited data on predictors of sICH in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation.

Methods:
We evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke center over a 30-month period. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH to identify independent predictors of sICH with p<0.1. We then derived an sICH prediction score and validated it using the Blood Pressure After Endovascular Treatment (BEST) multicenter prospective registry.

Results:
We identified 578 patients with acute ischemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: Thrombolysis in cerebral ischemia score, Alberta stroke program early computed tomography score (ASPECTS), and Glucose level, and using these predictors, we derived the weighted TAG score which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48-2.66, AUC=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22-1.79, AUC=0.69) cohorts.

Conclusion:
High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.
Abstract 117: Fixed Compared to Autoregulation-oriented Blood Pressure Thresholds After Mechanical Thrombectomy for Ischemic Stroke
Authors: Petersen Nils H , Silverman Andrew , Strander Sumita , Kodali Sreeja , Wang Anson , Sansing Lauren H , Schindler Joseph L , Falcone Guido J , Gilmore Emily J , Jasne Adam , Cord Branden , Hebert Ryan M , Johnson Michele H , Matouk Charles , Sheth Kevin N
Published: June 2021

Background:
Loss of cerebral autoregulation in the acute phase of ischemic stroke leaves patients vulnerable to blood pressure (BP) changes. Effective BP management after endovascular therapy (EVT) may protect the brain from hypo- or hyperperfusion. In this observational study, we compared personalized, autoregulation-guided BP management with two commonly used clinical approaches: (1) maintaining BP below a fixed, pre-determined value and (2) stratifying BP thresholds based on reperfusion status.

Methods:
We prospectively enrolled 90 patients undergoing EVT for stroke. Autoregulatory function was continuously measured by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in mean arterial pressure (MAP). The resulting autoregulatory index was used to trend the BP range at which autoregulation was most preserved. Percent time that MAP exceeded the upper limit of autoregulation (ULA) or decreased below the lower limit of autoregulation (LLA) was calculated for each patient. Time above fixed SBP thresholds was computed in a similar fashion. Functional outcome was measured with the modified Rankin Scale (mRS) at 90 days.

Results:
Personalized limits of autoregulation (LA) were successfully computed in all 90 patients (mean age 72
+
16, 47% female, mean NIHSS 14, mean monitoring time 28
+
18 hours). Percent time with MAP above the ULA associated with worse 90-day outcomes (OR per 10% 1.84, 95% CI 1.3-2.7, P=0.002), and patients suffering from hemorrhagic transformation spent more time above the ULA (10.9% vs. 16.0%, P=0.042). While there appeared to be a non-significant trend towards worse outcome with increasing time above SBP thresholds of 140 mmHg and 160 mmHg, the effect sizes were smaller compared to the personalized approach.

Conclusions:
Non-invasive determination of personalized BP thresholds for stroke patients is feasible. Deviation from these limits may increase risk of further brain injury and poor functional outcome. This approach may present a better strategy compared to the classical approach of maintaining SBP below a pre-determined value, though a randomized trial is needed to determine the optimal approach for hemodynamic management.