bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP109: Poly-ICLC-induced Blood Brain Barrier protection is independent of Toll-like Receptor 3 Signaling
Authors: Gesuete Raffaella , Packard Amy E , Vartanian Keri B , Stevens Susan L , Bahjat Frances R , Yang Tao , Stenzel-Poore Mary P
Published: March 2022

Introduction:
Preconditioning with a TLR3 ligand, polyinosinic polycytidylic acid (poly-ICLC), a synthetic dsRNA, protects against middle cerebral artery occlusion (MCAO). Using an in vitro model of the blood brain barrier (BBB) we found that Poly-ICLC stabilizes the BBB during ischemia through a mechanism involving IFNβ production from glial cells. We assessed the hypothesis that Poly-ICLC stabilization of the BBB and subsequent reduction of ischemic injury requires the presence of TLR3 on both endothelial and glial cells.

Methods:
BBB was modeled using a transwell co-culture system with primary brain microvascular endothelial cells (BMECs) in the upper chamber and primary mixed glial cells in the lower chamber. Poly-ICLC was administered 24h prior to 5h of oxygen glucose deprivation (OGD), which models stroke in vitro. Transendothelial electric resistance (TEER) and endothelial permeability were evaluated 24h after OGD and IFNβ secretion was assessed by ELISA. For in vivo studies, WT and TLR3
-/-
mice were treated with poly-ICLC or vehicle 72h prior to MCAO and infarct volume was determined after 24h of reperfusion.

Results:
Poly-ICLC administered exclusively to the upper chamber containing BMECs, results in secretion of IFNβ from glial cells in the lower chamber and significant protection against OGD. To determine whether BMEC or glial expression of TLR3 was required for protection we generated BBB models with TLR3 deficient (TLR3-/-) BMECs in co-culture with WT mixed glial cells as well as WT BMECs in co-culture with TLR3
-/-
mixed glial cells. Poly-ICLC preconditioning induced protection in the presence or absence of TLR3 suggesting that TLR3 signaling is not required for protection. This finding was supported further by in vivo data showing that poly-ICLC preconditioning protects TLR3
-/-
mice against ischemic injury.

Conclusions:
Our results showed that poly-ICLC interaction with endothelial cells induces IFNβ production in glial cells to confer protection. This process does not require TLR3 expression on endothelial or glial cells suggesting that other dsRNA receptors (MDA5 and RIGI) may be important in poly-ICLC-induced protection.
Abstract TMP112: F11 Receptor Antagonists As Therapeutic Agents For Atherosclerosis And Thrombosis
Authors: Babinska Anna , Li Yan , Jiang Xian-Cheng , Kornecki Elizabeth , Ehrlich Yigal , Salifu Moro
Published: March 2022

Rationale and Objective:
The F11 Receptor (F11R; aka Junctional Adhesion Molecule-A, JAM-A) is a cell adhesion protein present on the surface of circulating platelets and within tight junctions of endothelial cells (EC). We reported evidence for the critical role of F11R in the adhesion of platelets to cytokine-inflamed endothelium. Because platelet adhesion to an inflamed endothelium is one of the early steps of plaque formation in non-denuded blood vessels, we concluded that exposure of
de novo
synthesized F11R molecules on the luminal surface of EC is a crucial step in early stages of atherogenesis, leading to atherosclerosis, heart attacks and strokes. Utilizing recombinant F11R protein and F11R peptides, we have demonstrated that the expression of F11R on the luminal surface of inflamed EC initiates platelet adhesion to the inflamed EC thru binding of F11R molecules and this binding is inhibited by F11R antagonists. The present report provides new
in-vivo
evidence for the critical role of F11R antagonists in the formation of atherosclerotic plaques in apoE
-/-
mice.

Methods and Results:
The effect of F11R peptide on the formation of atherosclerotic plaques was determined in apoE
-/-
mice from 12 to 20 weeks of age. Fourteen apoE
-/-
mice were obtained from the Jackson Laboratory and fed a Western-type diet. Seven mice were injected with an F11R peptide (4.3 mg/100μl) every day for either a 3-, 4- or a 5- month period. Control animals were injected with diluent for the same period of time. The aortae and hearts were dissected and the aortic arch was photographed. An aortic lesion
en face
assay and morphometric lesion analysis was performed. Mice treated with the F11R peptide demonstrated healthy appearance with significantly decreased atherosclerotic lesion size as compared to unhealthy, control animals with large lesion sizes.

Conclusions:
F11R peptide inhibits the development of plaque formation in Apo E
-/-
mice, an animal model of atherosclerosis. The results of combined
in vitro
and
in vivo
studies provide information that development of small peptide analogs or peptidiomimetics which antagonize the pathological activity of F11R can be used as therapeutic agents for the prevention of atherosclerosis and thrombosis leading to heart attacks and strokes.
Abstract TMP16: Hypoperfusion Severity Is Associated With Poor Collaterals And Progresses Over Time
Authors: Olivot Jean Marc , Marks Michael P , Mlynash Michael , Wheeler Hayley M , Inoue Manabu , Kemp Stephanie , Straka Matus , Zaharchuk Gregory , Bammer Roland , Lansberg Maarten G , Albers Gregory W ,   DEFUSE 2 Investigators
Published: March 2022

Background:
We hypothesized that cerebral perfusion deficits are more severe in acute stroke patients with poor collaterals and that the severity would increase over time if reperfusion does not occur.

Methods:
This is a substudy of DEFUSE 2. Collaterals were assessed on conventional angiography and dichotomized as poor vs. good flow. DWI and PWI were performed before and within 12 hrs after endovascular therapy; PWI lesion volumes were determined using a Tmax>6sec threshold. The hypoperfusion ratio (HR) was calculated by determining the proportion of the PWI lesion that had severe Tmax delay (>10sec). Acute lesion growth was defined as the difference between the baseline and follow-up DWI volume.

Part 1: In patients with an ICA or M1 occlusion we compared the HR to the collateral score. An ROC curve assessed whether the HR predicts the collateral score.

Part 2: Among patients who did not experience early reperfusion, the difference between the baseline and follow-up HR was assessed and correlated with early infarct growth.

Results:
Part 1: Fifty six patients were eligible. Poor collateral flow was associated with larger baseline PWI lesion volume, p=0.012 and a higher HR compared to patients with good flow [median HR 45% (IQR: 35-52%) vs. 34% (IQR 14-41), p=0.003]. A HR > 41% predicted poor collateral flow with an AUC=0.73 (sensitivity 65%, specificity 78%, p=0.003).

Part 2: Thirty two patients who did not achieve reperfusion were included; PWI Tmax >6sec lesions volumes at baseline and follow-up were similar (median volume 75 mL at both time points). The median HR at follow-up was significantly higher than baseline [46% IQR (34-65) vs. 40% (24-48), p=0.007; median difference = 13% (IQR: 3.5-17)]. Patients who had worsening of their HR between baseline and follow-up were more likely to experience early ischemic lesion growth (R=0.53, p=0.002).

Conclusion:
The size and severity of Tmax lesions are associated with angiographic collateral scores. Patients who have a high percentage of their PWI lesion comprised of severe Tmax delays are likely to have poor collaterals. When early reperfusion is not achieved, the severity of hypoperfusion progresses and this progression is associated with early infarct growth.
Abstract TMP25: Rates Of Complications And Aneurysm Occlusion In Patients Undergoing Treatment Of Cerebral Aneurysms Utilizing Flow Diversion With The Pipeline Embolization Device And Algorithm Adjusted Antiplatelet Therapy
Authors: Dannenbaum Mark J , Schuette Albert J , Rutledge William C , McCracken David J , Skukalek Susana L , Case Daniel B , Webb Adam C , Asbury William , Tong Frank C , Dion Jacques E , Winkler Annie , Cawley Charles M
Published: March 2022

Introduction:
The need for therapeutic dual antiplatelet therapy in patients with cerebral aneurysms treated with flow-diverting stents increases the risk of thromboembolic and hemorrhagic complications. To balance these risks, we assessed patients for their responsiveness to dual antiplatelet therapy using a modified platelet aggregation study (PIPA). We hypothesized that double doses of clopidogrel or aspirin in patients with antiplatelet non-responsiveness would reduce the incidence of thromboembolic complications without increasing the incidence of hemorrhage or decreasing the rate of aneurysm occlusion.

Methods:
79 patients with 98 cerebral aneurysms were treated with the pipeline embolization device. All patients with a suboptimal PIPA received double doses of clopidogrel or aspirin prior to treatment. Aneurysm occlusion was categorized using the Roy-Raymond Occlusion Classification (RROC). Chi-square or Fisher’s exact tests were used for univariate analyses, and logistic regression was used to identify potential predictors of complications and aneurysm occlusion.

Results:
Seven patients had a major complication and 7 had a minor complication (8.9%). There were 3 cerebral ischemic strokes (3.8%) and 5 cerebral hemorrhages (6.3%). Thirty-eight patients had angiographic follow-up at 6 months. Of these, 18 patients were resistant to clopidogrel or aspirin, and 19 received double dose therapy prior to treatment. Double dose clopidogrel or aspirin was not associated with major, minor, cerebral ischemic or hemorrhagic complications. Twenty-one patients (55.3%) had complete occlusion of their aneurysms (RROC type 1), and 17 patients were categorized as RROC type 2 or 3 at 6 months. Treatment with double dose clopidogrel or aspirin was not associated with reduced occlusion (RROC type 2 or 3) in a univariate and multivariate analysis.

Conclusions:
In patients treated with flow-diverting stents, the risk of ischemia must be balanced with the risk of hemorrhage. We found that the use of double dose clopidogrel and aspirin in the setting of antiplatelet non-responsiveness is safe. It is not associated with increased hemorrhagic complications. Patients treated with double dose therapy did not exhibit a reduced aneurysm occlusion rate.
Abstract TMP45: Undiagnosed Diabetes and Pre-Diabetes among Stroke Survivors in the United States
Authors: Towfighi Amytis , Markovic Daniela , Ovbiagele Bruce
Published: March 2022

BACKGROUND:
The obesity epidemic has been associated with a surge in diagnoses of diabetes and pre-diabetes in the general population, but a high proportion of individuals are unaware that they have these conditions, which confer higher vascular risk, yet are amenable to treatment. Given the adverse effects of hyperglycemia on post-stroke outcomes and recurrent vascular risk, we investigated the burden of undiagnosed diabetes and pre-diabetes among stroke survivors.

METHODS:
We assessed prevalence of undiagnosed diabetes and pre-diabetes (HbA1c ≥6.5% and HbA1c 5.7-6.4% without self-reported physician-diagnosis) among 1070 non-pregnant adult (≥20 years) stroke survivors who participated in the National Health and Nutrition Examination Surveys 1999-2010. Logistic regression was used to assess the relationship between race-ethnicity and odds of undiagnosed diabetes/prediabetes, adjusting for sociodemographic characteristics and medical comorbidities.

RESULTS
Among an estimated 5,102,279 adult stroke survivors in the US, 3.7% had undiagnosed diabetes, while 32.3% had undiagnosed pre-diabetes. Prevalence of undiagnosed diabetes was 7.5% in non-Hispanic blacks (NHBs), 4.4% in Hispanics, and 3.1% in non-Hispanic whites (NHWs). Prevalence of undiagnosed pre-diabetes was highest in NHBs (37.8%), followed by NHWs (31.6%) and Hispanics (26.3%). Compared to NHWs and Hispanics, NHB stroke survivors with undiagnosed diabetes/pre-diabetes were younger (mean age 59 years vs. 70 and 67 years), more likely to be on antihypertensive medications (73% vs. 66% and 58%), and more likely to smoke (30% vs. 22% and 11%). After multivariate analysis, NHBs were more likely to have undiagnosed diabetes/pre-diabetes than NHWs (OR 2.12, 95% CI 1.31-3.44; p=0.002).

CONCLUSIONS:
A high proportion (one in 3) of stroke survivors in the US has undiagnosed pre-diabetes and the highest rates of diabetes and pre-diabetes are seen among NHBs, even after adjusting for confounders. Systematic screening and treatment at the time of the index stroke may boost overall clinical outcomes and bridge these racial disparities.
Abstract TMP79: The Accuracy of the FUNC score to Identify Poor Prognosis in Patients with Primary Intracerebral Hemorrhage
Authors: Garrett John S , Zarghouni Mehrzad , Layton Kennith , Daoud Yahya
Published: March 2022

Background & Purpose:
Recent studies suggest that intracerebral hemorrhage (ICH) clinical prediction scores (CPS) are not accurate enough to identify the cohort of patients with an extremely low chance of survival who would not benefit from further care. The early withdrawal of aggressive care, even in those with the poorest prognosis according to several CPS, has been demonstrated to be associated with worsened outcomes. Initial reports of one recently developed CPS, the FUNC score, suggest that it may more accurately identify this patient population. The aim of this study is to determine if application of do-not-resuscitate orders (DNR) within in the first 24 hours of admission impacted the prognosis of patients with predicted poor outcome.

Methods:
We retrospectively reviewed 501 consecutive patients with ICH who were admitted from the Emergency Department to a large healthcare system in Dallas, TX between 6/1/2009 and 6/1/2011. Patients with a predicted 100% chance of poor neurologic outcome (PNO) according to FUNC (<4) and ICH-GS(>10) scores were evaluated to determine if early DNR impacted 90 day survival or rate of survival with PNO, defined as Glasgow Outcome Score of <3.

Results:
Of the 501 patients with ICH, 104 were excluded due to a recognized etiology of their ICH. Data was not available in 31 patients. In the resultant 366 patients, the overall mortality at discharge was 114 (31%, 95% CI=27%-36%). Of the 68 patients who scored <4 on the FUNC, 67 (98.5%, 95% CI=92%-100%) had a PNO at discharge. Of these 68 patients, early DNR were present in 40 patients. The presence of early DNR was not associated with a significant difference in the rate of PNO at discharge (40/40=100% v. 27/28=96.4% p:0.42) or 90 day mortality (40/40=100% v. 21/28=75%, p:0.06). Of the 92 patients who scored >10 on the ICH-GS, 88 (95.6%, 95% CI=89.3-98.3) had a PNO at discharge. The presence of early DNR was associated with a significant difference in both the rate of PNO at discharge (48/48=100% v. 40/44=90.9%, p=0.048) and 90 day mortality (48/48=100% v. 34/44=77.3%, p:0.007).

Conclusion:
The FUNC score is able to accurately identify the subgroup of patients suffering from ICH with an extremely poor prognosis and little hope of survival to hospital discharge with good neurologic outcome.
Abstract TMP81: Cerebral Blood Flow and Blood Pressure Reduction Do Not Affect Perihematomal Edema Growth in Acute Intracerebral Hemorrhage
Authors: McCourt Rebecca , Gould Bronwen , Hill Michael D , Jeerakathil Thomas , Asdaghi Negar , Dowlatshahi Dariush , Coutts Shelagh B , Demchuk Andrew M , Shuaib Ashfaq , Emery Derek , Butcher Ken S
Published: March 2022

Background:
Both vasogenic and cytotoxic (ischemic) processes have been postulated to play a role in perihematoma edema formation. In the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), cerebral blood flow (CBF) was measured in ICH patients assigned to systolic blood pressure (SBP) targets of <150 or <180 mmHg. In this secondary analysis, we tested the hypotheses that edema growth is associated with reduced CBF and lower SBP.

Methods:
Non-contrast CT scans were obtained at baseline, 2h and 24h post-randomization. Mean relative CBF (rCBF) in the perihematoma region was calculated from raw CT Perfusion data obtained at 2h. Edema volume was measured using planimetric techniques and a Hounsfield unit threshold of ≤24 at baseline and 24h.

Results:
ICH patients were randomized (n=33 per group) at a median (IQR) of 7.6 (12.8) h after symptom onset. Mean SBP was significantly lower in the <150 mmHg (139±21 mmHg) than the <180 mmHg (163±11, p=<0.0001) at the time of CTP. Mean perihematoma rCBF in the <150 mmHg group (0.85±0.12) was similar to that in the <180 mmHg group (0.88±0.09, p=0.34). Treatment groups were balanced with respect to baseline SBP (180±18 vs. 185±25 mmHg, p=0.39) and acute ICH volume (20.7±22.0 vs. 28.0±25.8 ml, p=0.22). In all patients, median edema volume increased significantly between the baseline 1.8(2.5) ml and 24 h scans (3.1 (5.1) ml, p<0.0001). Linear regression indicated that ICH expansion predicted edema growth (β =0.3 [0.0, 0.2]). Lower perihematoma rCBF did not predict edema growth independently of ICH expansion (β =-0.2 [-229.5, 0.4]). Mean edema growth in the <150 group (2.4±6.9) was similar to that in the <180 group (2.9±6.4, p=0.737). Edema growth was not predicted by SBP change (β=0.12 [-0.45, 1.22]). Neither low SBP load (fraction of time SBP<150 mmHg over 24 h; β=0.07 [-0.13, 0.24]) nor high SBP load (time SBP >180 mmHg; β=0.07 [-0.13, 0.24]) predicted edema growth.

Conclusion:
Perihematoma edema growth is explained by ICH volume expansion. Lower perihematoma CBF and BP treatment do not exacerbate edema growth. These data are not consistent with a cytotoxic mechanism of edema formation and support the safety of early BP treatment.
Abstract TMP86: Evaluation of NIHSS Application Program to Stroke Nurses
Authors: Han Jung-Hee , Kim Kyoung-Ok , Lee Gee-Eun , An Young-Hee
Published: March 2022

Background and purpose:
Neurologic assessment for stroke nurse is very important, since exact examination and finding for neurologic symptoms greatly affect prognosis of stroke. NIHSS is a tool to best reflect neurologic status for acute ischemic stroke and this is mostly measured by neurologists. Although the closest medical team member is a nurse, indeed there are not many hospitals where a nurse measures NIHSS and related researches are also insufficient. The purpose of this study is to evaluate quality of nursing as NIHSS Application Program (NAP) to stroke nurses.

Methods:
NAP was performed from April to July, 2010 as following. Theoretical and practical educations for NIHSS by a stroke clinical nurse specialist were performed for stroke nurses and they completed learning for video lectures and certification individually by website. NIHSS was measured every shift and integrated with electrical medical records. This research compared medical records before and after NAP and set participants who were hospitalized in acute stroke unit through emergency room and diagnosed ‘ischemic stroke’. Pretest group (n=100) was set from January to March, 2009 and posttest group (n=115) was set from January to March, 2011. Pearson’s t-test and chi-square test were used to measure differences between two groups.

Results:
Nursing records for neurologic assessment items were all increased (50% versus 95%,
p
=.008). Especially items for ‘neglect, dysarthria, visual disturbance, pupil status, and EKG’ were significantly increased. Number of notified cases for neurologic changes by nurse was increased (21% versus 39%,
p
=.004). Most of notified reasons were focused on ‘limb motor function’ in pretest group while items for ‘alertness/awareness, facial palsy, limb ataxia’ were newly reported for posttest group. Among notified cases, patients detected extensions of stroke lesions (6% versus 10%,
p
=.000) and patients treated induced hypertension therapy were both increased (13% versus 22%,
p
=.000).

Conclusions:
NAP improved nurses’ degree of knowledge for stroke patients and this contributed to prevention of deterioration of stroke. It is widely needed to apply NIHSS by stroke nurses for quality of nursing.
Abstract TMP91: How Reliably Do Clinicians Predict Stroke Outcomes? Results from the JURaSSiC (Clinician JUdgment vs. Risk Score to predict Stroke outComes) randomized trial.
Authors: Saposnik Gustavo , Cote Robert , Mamdani Muhammad , Thorpe Kevin , Raptis Stavroula , Fang Jiming , Redelmeier Donald , Goldstein Larry B ,   on behalf of JURASSiC (Clinician JUdgment vs. RiskScore to predict Stroke outComes) Investigators,   for the Stroke Outcomes Rsch (SORCan - ) Working Group
Published: March 2022

Background:
Limited information is available evaluating the accuracy of clinician judgment compared with predictive stroke outcome scores.

Objectives:
To compare the accuracies of clinician judgment and a validated stroke risk score (iScore) for predicting stroke patient outcomes.

Methods:
A convenience sample of 111 practicing clinicians (general and stroke neurologists, internists, and ER physicians) predicted the outcomes of 5 stroke patients based on case summaries. Cases were randomly selected as being representative of the 10 most common clinical scenarios (n=1,415) from a pool of over 12,000 patients admitted to stroke centers in Ontario, Canada. Stroke cases had known clinical presentation, comorbidities, stroke severity, and outcomes.

Main outcomes:
30 day mortality and/or disability at discharge.

Results:
Evaluators’ mean age was 40±12 years; 55 (50%) were active staff physicians, 47 (42%) neurologists and 8 (7%) board certified stroke neurologists. The mean number of stroke patients assessed per physician/yr was 98 (±150); 92 (82%) provide acute stroke care (initial 48 hrs). Although on average clinicians were able to estimate stroke patient outcomes accurately (mean absolute difference for death or disability at discharge: 12.8%; 95%CI 9.3%-16.5%) ,there was significant variability in the clinicians’ predictions (Figure A). Specifically, 70-100% of clinicians’ estimates were outside the 95%CI of observed outcomes (Figure B). In contrast, 90% of the iScore-based estimates were within the 95%CI of observed outcomes. Clinicians indicated a low level of confidence (mean 39%) in estimating outcomes.

Conclusions:
Clinicians with expertise in stroke care made predictions for actual outcomes outside of the 95%CI in 70-100% of cases whereas predictions using the iScore fell outside the 95%CI in less than 10% of cases. The iScore may provide a useful tool to help clinicians gauge a stroke patient’s likely outcome.
ClinicalTrials.gov
NCT01657279
Abstract TP108: 2,2 Dipyridyl, An Iron Chelator, Does Not Reduce Intracerebral Iron Toxicity Or Improve Outcome After Intracerebral Hemorrhagic Stroke In Rats
Authors: Caliaperumal Jayalakshmi , Wowk Shannon , Jones Sarah , Ma Yonglie , Colbourne Frederick
Published: March 2022

Background —
After an intracerebral hemorrhage (ICH) iron is released from degrading erythrocytes over days, which causes secondary damage by increasing free radicals. Many studies show that iron chelators, such as deferoxamine, lessen injury, but not all studies support this.

Hypothesis —
The ferrous iron chelator, 2,2 Dipyridyl (DP), will decrease injury after ICH or intraparenchymal FeCl
2
infusion in rats.

Experiment 1—
Rats were given a collagenase-induced striatal ICH. In experiments 1 and 3, we tested whether behavior was improved (e.g., walking) from administering DP (25mg/kg/day, 12 hours after surgery for 3 days). They were euthanized after 7 days to determine non-heme iron levels in the brain.

Experiment 2—
Rats were injected with DP (20mg/kg) 6 hours after collagenase infusion and every 24 hours till euthanasia at 3 days for measuring edema.

Experiment 3—
After injecting FeCl
2
in the striatum rats were given DP (25mg/kg every 12 hr starting 2 hours prior to surgery for 3 days). The volume of tissue loss and Fluoro-jade staining (degenerating neurons) was measured.

Results —
DP did not improve behavioral or histological outcome or reduce edema in either the collagenase ICH or FeCl
2
model. DP also did not affect parenchymal non-heme iron level.

Conclusion —
Our data suggests that DP on its own is not an effective strategy for ICH.
Abstract TP11: National Trends in Utilization and Outcomes of Emergent Carotid Artery Stent Placement in Acute Ischemic Stroke Patients
Authors: Hassan Ameer E , Adil Malik A , Zacharatos Haralabos , Grigoryan Mikayel , Chaudhry Saqib A , Tekle Wondwossen G , Khatri Rakesh , Qureshi Adnan I
Published: March 2022

Background:
Subsequent to recent trials of carotid artery stent placement (CAS), emergent stent placement in acute ischemic stroke is being considered more frequently as part of the endovascular treatment.

Objective:
To evaluate trends in utilization of emergent CAS in acute ischemic stroke and to compare rates of death and disability with those treated with endovascular treatment without CAS.

Methods:
We obtained data for patients admitted to hospitals in the United States between 2004 to 2009 with a primary diagnosis of ischemic stroke using the Nationwide inpatient sample, a nationally representative data of acute care hospitalizations. We determined the rate of utilization of emergent CAS as part of endovascular treatment and outcomes according to use of emergent CAS or not. Outcomes were classified as minimal disability, moderate to severe disability, and death based on discharge disposition.

Results:
Of the 12,720 patients who underwent endovascular treatment, 1000 patients had emergent CAS (mean age 65 ± 12.8 years). The estimated number of patients undergoing emergent CAS increased by 7 fold (46 in 2004 to 336 in 2009). The rates of intracranial hemorrhage remained unchanged throughout the 6 years. The rates of none-minimal disability were significantly higher (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.3-3.1, p value=0.001) and in-hospital mortality was significantly lower [OR 0.6, 95% CI 0.4-0.9, p value=0.009] among patients who underwent endovascular treatment with emergent CAS after adjusting for potential confounders.

Conclusion:
There has been a significant increase in the proportion of acute ischemic stroke patients receiving emergent CAS with high rates of favorable outcomes and low rates of in-hospital mortality.
Abstract TP143: Early Angiographic Neovascularization Response to EDAS Surgery in Adults with Intracranial Arterial Stenosis
Authors: Dusick Joshua R , Mayor Fernando , Liebeskind David , Saver Jeffrey L , Gonzalez Nestor
Published: March 2022

Introduction:
Significant neovascularization following indirect revascularization procedures, such as encephaloduroarteriosynangiosis (EDAS), has traditionally been considered to develop slowly over time. However, a recent study of angiography following indirect revascularization procedures demonstrated early signs of revascularization as early as 4 days following surgery. While we have previously published demonstration of robust revascularization at 6 months and later following surgery, here we present a subset of patients, all with non-moyamoya intracranial arterial stenosis (IAS), with earlier angiographic evaluation following EDAS.

Methods:
We retrospectively reviewed charts of adult patients who have undergone EDAS for non-moyamoya IAS. These early angiograms were evaluated for signs of revascularization and graded according to the scale presented by Perren et al (1, no sign of neoangiogenesis; 2, one-to-four new transcortical vessels; 3, > four new transcortical vessels).

Results:
Ten patients (mean age 43 years, 8 females) were found with follow-up cerebral angiography within 6 months of surgery (1 each at 1, 2 & 3 mo, 2 at 1.5 mo, 3 at 5 mo, and 4 at 6 mo). All angiograms demonstrated neovascularity, regardless of underlying diagnosis, including scores of 3 (extensive neoangiogenesis) in 80% of cases as early as 1.5 months after surgery. Two patients had grade 2 at 1 & 2 months. Clinically, all patients’ ischemic symptomatology has resolved. Six patients have had no symptoms since surgery while 4 patients had transient episodes consistent with ischemia (TIA) that all resolved by 2 weeks post-operatively (3 at 1 week and 1 at 2 weeks). No patient suffered stroke following EDAS.

Conclusion:
This series adds to the growing evidence that indirect revascularization procedures can lead to significant neovascularity in a shorter time frame than previously expected in adult patients, including those with non-moyamoya IAS. Further study is required to better define the time course of neoangiogenesis and to evaluate angiogenic mechanisms that contribute to the success of this procedure.
Abstract TP147: How Different Vascular Pathologies Of Penetrating Artery Disease And Large Parent Arterial Disease Are Associated With Progressive Motor Deficits.
Authors: Yamamoto Yasumasa , Nagakane Yoshinari
Published: March 2022

Background and Purpose:
Penetrating artery infarcts (PAI) are caused by two different vascular pathologies those include atheromatous occlusion at the orifice of large caliber penetrating arteries termed branch atheromatous disease (BAD) and lipohyalinotic degenerative changes termed lipohyalinotic degeneration (LD). PAI are sometimes accompanied by underlying large parent arterial disease (LPAD). We investigated the relationship between 2 different atheromatous lesions, BAD and LPAD, and how 2 lesions may associate with progressive motor deficits (PMD).

Subjects and methods:
We studied consecutive 568 patients with acute PAI in the territories of the lenticulostriate artery (LSA) (n=373) or paramedian pontine arteries (PPA) (n=195). The LPAD was defined as middle cerebral artery atherosclerosis responsible for LSA infarct or basilar artery atherosclerosis for PPA infarct evaluated by MRA. BAD of the LSA was defined as infarcts visible for 3 or more axial slices at a slice thickness of 7 mm and that of the APA was unilateral infarcts extending to the basal surface of the pons. Other type than BAD were categorized as LD. Finally, patients were classified into 4 groups: G1. LD type infarct in the territory of LSA (n=208), G2. BAD type in the LSA (n=164), G3. LD type in the PPA (n=69), G4. BAD type in the PPA (n=122). PMD was defined as worsening by ≥1 point in the motor item of the NIHSS.

Results:
The prevalence of LPAD in 4 groups was as follows: G1; 12 (5.7%), G2; 48 (29.2), G3; 14 (20.2), G4; 68 (55.7). PMD in 4 groups was as follows: G1; 25 (12.0%), G2; 78 (47.5), G3; 8 (11.5), G4; 42 (34.4). Logistic regression analysis was performed estimating G1 as reference to calculate the odds ratio of each group for PMD. Univariate analysis: G2; 6.7 (P<0.0001), G3; 0.91 (0.86), G4; 5.5 (P<0.0001). The odds ratio of LPAD for PMD are 2.9 (0.0002) in LSA group and 1.4 (0.25) in PPA group. Multivariate analysis: odds ratio of G2 and LPAD for PMD were 6.0 (p<0.0001) and 1.6 (p=0.13) in LSA group, and that of G4 was 6.1 (p=0.0006).

Conclusion:
BAD and LPAD were strongly associated each other. Although BAD were significantly correlated with PMD in both territories of LSA and PPA, LPAD was not significantly associated with PMD. BAD, rather than LPAD, appears to be more crucial for PMD in acute PAI patients.
Abstract TP182: Bone Mass Loss May Be A Predictor Of Silent Cerebral Infarct And Cerebral White Matter Change In Community-dwelling Adults Without Stroke And Dementia.
Authors: Suk Seung-Han , Hwang Sung-Hee , Do Seung-Yoen , Kang Ji-Sook , Lee Jun-Hong , Minn Yangki , Koh Im-Seok , Park Jae-Hyun
Published: March 2022

Background:
Loss of bone and muscle mass, fall and fractures are common conditions after stroke. Possible association between reduced bone density and cognitive impairment in postmenopausal women are well recognized. However, the relationship between bone mass loss and silent infarcts and cerebral white matter changes remains unknown.

Methods:
Bone densitometry measured by Dual-energy X-ray absorptiometry of lumbar spine and hip and brain CT scan were performed for 650 subjects (458 female, mean age 63±7.8 years; 192 male, 61.5±8.5 years) among 650 stroke- and dementia-free adults older than 50 years recruited for early health check-up program, a part of PRESENT project between January 2009 and December 2010. Assessment of vascular risk factors and physical examination by in-person interview and were also taken by neurologist, and trained nurses.

Result:
In unadjusted analysis, the odds ratio (OR) for silent cerebral infarcts and/or cerebral white matter changes in men with osteoporosis was 3.8 (95% CI, 1.62-8.86; p = 0.002) and 2.2 (95% CI, 1.35-3.53; p=0.002) in women as compared to subjects with normal bone density. Even after adjustment for age, education, hypertension, DM, hypercholesterolemia, and current smoking, the OR was 3.8 (95% CI, 1.43-10.3; p = 0.008) for men and 1.9 (95% CI, 1.10-3.18; p=0.02), for women.

Conclusion:
These findings suggest that loss of bone mass may be a predictor of silent cerebral infarcts and cerebral white matter changes in community dwelling, apparently healthy adults.
Abstract TP185: Framingham Score Predicts Short-Term Risk of Major Clinical Events after a Recent Stroke
Authors: Ovbiagele Bruce , Nguyen-Huynh Mai , Hills Nancy K
Published: March 2022

Background:
Identifying patients with a recent stroke at high risk for future major vascular events may provide opportunities to improve clinical outcomes. Although Framingham Coronary Risk Score (FCRS) predicts major coronary events over 10 years in the general population free of symptomatic vascular disease, few studies have examined its role as a prognosticator after stroke. We assessed the link between the baseline FCRS and major clinical events among patients with a recent stroke.

Methods:
We analyzed data on ischemic stroke patients enrolled in a randomized quality improvement trial of secondary stroke prevention, conducted in 14 Kaiser Permanente hospitals in Northern California between January 2004 and September 2006. Electronic records from the index hospitalization and for 6 months following hospitalization were reviewed. Framingham Risk Scores (FRS) were calculated for each patient but all patients >74 years of age (the upper age limit included in the FRS) were excluded from the analysis. FRS scores were dichotomized into high (≥20%) and low (<20%) risk according to gender guidelines. The primary outcome was recurrent stroke, myocardial infarction and all-cause mortality after hospital discharge; and secondary outcomes were any stroke and any MI. Analyses were adjusted for age, gender, race, BMI, serum lipid levels, and discharge prescription of antithrombotics and statins.

Results:
Among 1667 patients discharged alive, mean age was 62.9 (8.6), 46% were male, 58% white, 32% had high FCRS. In adjusted analyses, high FCRS scores were associated with Black race (vs. White), higher BMI, and elevated serum triglycerides. Compared to those with low FCRS, high FCRS was associated with higher odds of the composite primary outcome 1.50 (1.16-1.93, p=0.002) and any recurrent stroke 1.53 (95% CI 1.18-1.98, p=0.001), but not any MI 1.14(95% CI 0.42-3.14, p=0.79). Additionally adjusting for age slightly attenuated these results, but did not change the significance level. A low incidence of MI (12 cases) resulted in a lack of power for this outcome.

Conclusions:
A baseline FRCS>20% predicts higher short-term risk of major clinical events in recent ischemic stroke patients.
Abstract TP187: Risk of Subarachnoid Hemorrhage among Patients Infected with Human Immunodeficiency Virus
Authors: Zacharatos Haralabos , Rahim Basit , Adil Malik M , Hassan Ameer E , Gilani Sarwat I , Qureshi Adnan I
Published: March 2022

Background:
In the current literature, subarachnoid hemorrhage data among patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) is limited to case reports.

Objective:
To compare the incidence and relative risk of subarachnoid hemorrhage (SAH) in patients with AIDS to those who are HIV negative, on a national level.

Method:
The Nationwide Inpatient Sample (NIS 2002-2010) was used to identify and all patients presenting with the primary diagnosis of SAH in the United States between 2002 and 2009. Among this cohort, we identified the patients with HIV/AIDS and those who were HIV negative and further stratified them based on gender and age: 13-24 years, 25-34 years, 35-44 years, 45-54 years and 55+ years. We obtained the number of people living with AIDS in the United States population from the Centers for Disease Control and Prevention (CDC) for 2002 according to the same age groups. Using the 2000 United States census information we identified the number of people in the general population and subtracted the AIDS cases within the respective age group. The relative risk of developing a SAH in patients with AIDS versus the HIV negative patients was also obtained between 2002 and 2009.

Result:
The age adjusted annual incidence of SAH was 62.3 per 100,000 and 20.2 per 100,000 among HIV/AIDS positive persons and HIV negative persons. The age adjusted annual relative risk for SAH among the HIV/AIDS positive persons was 3 (95% confidence interval 2.4 to 3.8). HIV positive women had higher incidence of SAH when compared to HIV positive males except for the 13-24 year old group. The SAH rate ratio decreased with each increasing decade when compared with HIV negative patients: 13-24 years (25), 25-34 years (8.6), 35-44 years (3), 45-54 years (2.4) and 55+ years (1.6). The 7 year incidence rate of SAH in HIV positive men between 13-24 years was 29 times more than in HIV negative men; similarly, the incidence of SAH among HIV positive women was 18 times that of HIV negative women.

Conclusion:
HIV/AIDS positive persons, particular young individuals, appear to have an increased risk of developing SAH.
Abstract TP195: Tobacco And Stroke Among Active and Prior Cocaine Users: An Avenue For Prevention.
Authors: Fehnel Corey R , Ayres Alison , Rost Natalia S
Published: March 2022

Background:
We characterized stroke mechanisms and risk factors in a cohort of cocaine users across a broad range of socioeconomic status to inform stroke management and prevention efforts.

Methods:
Cases were consecutive patients ≥ 18 years with acute ischemic stroke (AIS) and enrolled into a prospective registry, with history or laboratory confirmed cocaine use. Non-cocaine user AIS controls matched for age, sex, and race were derived from the same study population (2:1 ratio). Demographic, risk factor, and clinical data were collected prospectively. TOAST subtypes were assigned. Admission brain MRIs were used to assess infarct size and location. Multivariate logistic regression model for variables showing univariate association with cocaine use at p <0.2 was used to identify independent predictors of cocaine-associated AIS.

Results:
Between 2007-2010, we identified 91 cases and 182 controls (mean age 50.1±10.4 years; 73.6% male). Cases did not statistically differ from controls by income ($49,499 ±15,494 vs. $51,818±16,776), occupation (52% in “service/clerical”), or educational level (42.5% high-school graduates)(all p>0.5). Stroke severity was similar in both groups (median NIHSS 5, IQR 1-8 vs. 5.7, IQR 1-8, p=0.3) as was acute DWI volume (median 33.6cc, IQR 5-20 vs. 21.2cc, IQR 5-20; p=0.5), and proportion of patients treated with IV tPA (12% vs. 17%, p=0.4). Active tobacco use was significantly greater in cocaine-associated AIS (84% vs. 6%, p< 0.001). In multivariable analysis, tobacco use (OR 3.9, 95% CI 2.0-7.5), history of migraine (OR 2.5, 95% CI 1.1-5.9), and cardioembolic stroke subtype (OR 2.52, 95% CI 0.6-0.9) were independent predictors of cocaine-associated AIS. Subset analysis of toxicology confirmed (“active”) cocaine users (n=29) with AIS compared to non-cocaine using controls (n=58) from the same population. Association between cardioembolic stroke subtype (p<0.004) persisted. Active tobacco use emerged as a robust predictor of cocaine-associated stroke (OR 12.9, 95%CI 3.7-44.4) in this subset.

Conclusions:
Active tobacco use is an independent predictor of stroke among both active and past cocaine users. Stroke prevention campaigns should target broader audiences for smoking cessation and cocaine use prevention.
Abstract TP21: Impact Of Complete Recanalization On The Relationships Between Pretreatment Dwi Volume And Clinical Outcome In Patients Treated By Endovascular Treatment.
Authors: Olivot Jean Marc , Labreuche Julien , Inoue Manabu , meseguer elena , Mlynash Michael , rouchaud aymeric , mosimann pascal , klein isabelle , Straka Matus , Bammer Roland , Amarenco Pierre , Albers Gregory W , Mazighi Mikael
Published: March 2022

Objectives:
To evaluate the relationships between pre-treatment DWI volume and clinical outcome following endovascular therapy.

Methods:
Patients from the REcanalisation using Combined intravenous Alteplase and Neurointerventional ALgorithm for acute Ischemic StrokE (RECANALISE) study who suffered an acute hemispheric infarction with a large vessel occlusion and underwent DWI before endovascular treatment were enrolled. DWI volumes were automatically calculated by the RAPID software. Recanalization was graded using the TIMI scale. Outcomes assessed were favorable outcome (mRS 0-2) and death at 90 days. Findings: 66% (138/210) of the patients were eligible for this substudy. Mean age was 69.6 years (+/-17.6), median NIHSS 16 (IQR: 10-21) median time to MRI 110 min (IQR 77-178), and median time to treatment 149 min (IQR: 115-250). Median DWI volume was 14mL (IQR: 5 to 43) and was categorized into tertiles.Median volume per tertile were: Small: 3mL(IQR:1-5); Moderate 14mL(IQR:10-20) and Large 60mL(IQR:43-104)including 19 patients with a very large DWI lesion (>70mL). TIMI 3 was achieved in 47%[median delay 238 min, (IQR, 206 to 285)]and TIMI 2 in 38%; [median delay 269 min, (IQR, 219 to 350)]. Overall, the rate of favorable outcome decreased and the death rate increased gradually with DWI volume.( cf Table) After adjustment for age and NIHSS, complete recanalization was associated with a higher rate of favorable outcome and decreased death rate in the moderate and large DWI volume tertiles.(cf table)This relationship was not observed in patients with very large (>70 mL) or small DWI volumes.

Conclusion:
In patients undergoing endovascular treatment, our results demonstrate that increasing DWI volumes were associated with a worse outcome while a complete recanalization was associated with a significant better clinical outcome in patients with a moderate to large DWI lesion. This relationship was not observed in small or very large DWI lesion volume (>70 mL). />
Abstract TP24: Time from Symptoms Onset to Revascularization: Impact on Outcomes in Revascularized Swift Trial Patients
Authors: Zaidat Osama , Lazzaro Marc A , Brown Scott , Nogueira Raul G , Gupta Rishi , Jovin Tudor , Siddiqui Adnan , Yavagal Dileep , Clark Wayne , Saver Jeffrey L ,   For the SWIFT Investigators
Published: March 2022

Introduction:
Time from symptoms onset to revascularization (TOR) has been shown to be is an important predictor of clinical outcomes in mechanical thrombectomy for acute ischemic stroke (AIS). In this study, we sought to assess the influence of TOR on outcomes in the multicenter, randomized Solitaire FR with the Intention for Thrombectomy (SWIFT) trial.

Methods:
AIS patients enrolled in the SWIFT trial who achieved the primary endpoint of successful recanalization without hemorrhage (SR-sICH) were included. The TOR was the main predictor variable. The main outcome variables were the 90 days modified Rankin’s Scale (mRS) ≤ 2; good neurologic outcome (Rankin’s Scale (mRS) ≤ 2 or NIHSS Improvement of ≥10), and mortality. P-values were calculated using Wilcoxon, linear regression, Cochran Mantel-Haenzsel, or Fischer exact tests.

Results:
A total of 63 patients achieved SR-sICH and were included in this analysis. 57% patients had a good clinical outcome of mRS ≤ 2, with a mean TOR of 310(74) minutes vs. 348(80) minutes in those with mRS>2 at 90 days, p=0.08. Patients who died (19%) had a statistically longer TOR than survivors (TOR of 270(75) minutes versus 320(75) minutes in the survivors, p=0.04). Patients in lower quartiles had a trend toward improved neurological outcome and mortality (p=0.2 and p=0.1). When dichotomizing TOR to ≤6.5 hours (n=50) versus >6.5 hours (n=13), a trend toward better clinical outcome was noted in the ≤ 6.5 hours group; mRS ≤ 2 at 90-day (46% vs. 17%, p=0.008); with a trend toward improved good neurological outcome and mRS at 90 days (66% and 55% with p=0.19 and p=0.1, respectively) with no difference in mortality. A multivariate analysis model for predicting mRS at 90 days showed TOR as a significant predictor of neurological outcome (p=0.02).

Conclusions:
A shorter time from TOR is associated with improved functional neurological outcome at 90 days in revascularized SWIFT trial patients.
Abstract TP255: Interferon-Induced Peptide With Tetratricopeptide Repeats 1 Is a Key Mediator of Neuroprotection Induced by Preconditioning
Authors: Vartanian Keri B , Conrad Valerie K , Stevens Susan L , McDermott Jason E , Liu Mingyue , Stenzel-Poore Mary P
Published: March 2022

Introduction:
Preconditioning is the phenomenon whereby a low dose of a harmful stimulus provides robust protection against injury due to subsequent cerebral ischemia. We have evaluated transcriptional responses in three distinct preconditioning paradigms [lipopolysaccharide (LPS), CpG, brief ischemia] to create an inferred network of the neuroprotective genomic responses to stroke in mice. Topological analysis of this network identified interferon-induced peptide with tetratricopeptide repeats 1 (IFIT1) as a key transition point between clusters of genes, which suggests that IFIT1 is significant in this biological process. IFIT1 has been shown to function as a regulator of protein translation and transcription factor activity, although a role in ischemic injury has not been identified. We hypothesized that IFIT1 is required for neuroprotection against ischemic injury in the setting of preconditioning.

Methods:
We analyzed the regulation of IFIT1 and its inferred first-order network (genes directly linked to IFIT1) using mouse brain microarray data 3, 24, and 72 h following preconditioning and 3 and 24 h following middle cerebral artery occlusion (MCAO, n=4/treatment/timepoint, ~100 microarrays). In addition, IFIT1 deficient mice were preconditioned with LPS 72 h prior to MCAO and percent infarct was determined.

Results:
Network analysis revealed that IFIT1 and its first-order network are induced 24 h following stroke in preconditioned mice but not in mice given a stroke in the absence of preconditioning. This result suggests that IFIT1’s first-order network is associated with neuroprotection. Interestingly, IFIT1’s first-order network contains several interferon-associated genes, which are known to contribute to neuroprotection induced by preconditioning. Further support for a fundamental role for IFIT1 is evinced by our finding that IFIT1 deficient mice preconditioned with LPS are not protected against subsequent MCAO.

Conclusion:
IFIT1 is essential for neuroprotection induced by LPS preconditioning and may play an instrumental role in mediating an endogenous neuroprotective response to stroke.