bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP102: Loss of Laminin-α5 From Mural Cells Attenuates Ischemia-reperfusion Injury
Authors: Nirwane Abhijit , Nguyen Benjamin , Miner Jeffrey , Yao Yao
Published: January 2019

Introduction:
Laminin-α5, a major component of the basement membrane, participates in embryogenesis and vascular maturation. In the vasculature, laminin-α5 is predominantly synthesized by brain microvascular endothelial cells and mural cells. With distinct laminin β and γ chains, these cells make different α5-containing laminin isoforms. It has been shown that although dispensable for blood-brain barrier (BBB) maintenance under homeostatic conditions, endothelial laminin-α5 actively regulates inflammatory cell infiltration into the brain in pathological conditions. The function of mural cell-derived laminin-α5, however, remains unknown. Here, we investigated the roles of mural cell-derived laminin-α5 in BBB maintenance under homeostatic conditions and disease progression/outcome in ischemic stroke.

Methods:
Laminin-α5
flox/flox
mice were crossed with the Pdgfrβ-Cre
+
transgenic line to generate mural cell-specific laminin-α5 deficient mice (α5-PKO). BBB permeability and cerebral blood flow were measured in α5-PKO mice and their littermate controls under homeostatic conditions. In addition, these mice were subjected to 45 minutes of middle cerebral artery occlusion followed by reperfusion. At various time points after injury, brain infarct volume,neurologicalfunction, body weight loss, neuronal death, brain edema, BBB integrity, inflammatory cell extravasation, and hemorrhagic transformation were examined.

Results:
Comparable BBB integrity and cerebral blood flow were found in control and α5-PKO mice under homeostatic conditions. After ischemia-reperfusion injury, α5-PKO mice displayed smaller infarct volume, improved neurological function, attenuated body weight loss, reduced neuronal death, decreased brain edema, ameliorated BBB disruption, diminished inflammatory cell infiltration, and less severe hemorrhagic transformation.

Conclusions:
These results demonstrate that mural cell-derived laminin-α5 is dispensable for BBB maintenance and cerebral blood flow under homeostatic conditions, and that α5-PKO mice are profoundlyresistant to ischemic stroke, possibly through enhanced vascular integrity. These findings highlight a detrimental role of mural cell-derived laminin-α5 in ischemic stroke.
Abstract TMP105: Elevation of VEGF Exacerbates Hemorrhage in Mouse Brain Arteriovenous Malformation
Authors: Ma Li , Cheng Philip , Shaligram Sonali , Walker Espen J , Yang Shun-Tai , Tang Chaoliang , Zhu Wan , Li Qiang , Zhu Xiaonan , Su Hua
Published: January 2019

Background and purpose:
High level of VEGF has been implicated in bAVM bleeding and rupture through analyzing the VEGF levels in patients’ blood and in surgically resected bAVM specimens. However, the direct evidence is missing. Using a mouse bAVM model, we tested the hypothesis that elevation of focal VEGF level exacerbates the severity of bAVM hemorrhage.

Methods:
Brain AVMs were induced in adult mice that have
Alk1
(an AVM causal gene) exons 4-6 floxed by injection of an adenoviral vector expressing Cre-recombinase (Ad-Cre) and an adeno-associated viral vector expressing human VEGF (AAV-VEGF) into the basal ganglia. Two doses of AAV-VEGF, 5x10
9
(high) or 2x10
9
(low) viral genomes were used. In addition, the common carotid artery and jugular vein were anastomosis in a group of mice treated with low dose AAV-VEGF 6 weeks after the model induction to induce venous hypertension (VH), because VH increases VEGF level in the brain. Hemorrhages in the bAVM lesions were quantified on brain sections stained with Prussian blue, which detect iron deposition 8 or 9 weeks after model induction. VEGF levels were quantified by ELISA.

Results:
Compared to mice injected with low dose AAV-VEGF, mice injected with high dose of AAV-VEGF had a higher level of VEGF, larger Prussian blue positive areas in the bAVM lesion at 8 and 9-weeks after model induction (P<0.0001). In the low dose AAV-VEGF group, 69% mice had bAVM hemorrhage, while in the high dose AAV-VEGF group, 100% mice had bAVM hemorrhage. VH increased bAVM hemorrhage in low dose AAV-VEGF group. The overall mortality of bAVM in the high dose AAV-VEGF group was 26.7%, while no mouse died in the low AAV-VEGF group. VH caused a 50% mortality in low dose AAV-VEGF group.

Conclusion:
Using mouse bAVM models, we demonstrated that the evaluation of VEGF level through viral vector mediated overexpression of VEGF or create VH increases bAVM hemorrhage and mouse mortality.
Abstract TMP106: Intestinal Barrier Leakage Exacerbates Cerebral Cavernous Malformation Development in Murine Models
Authors: Shenkar Robert , Tang Alan , Gallione Carol , Moore Thomas , Lightle Rhonda , Girard Romuald , Hobson Nicholas , Cao Ying , Koskimäki Janne , Peiper Amy , Pardo Heidy , Griffin Erin , Dalldorf Delaney , Marchuk Douglas , Kahn Mark , Awad Issam
Published: January 2019

Introduction:
A serendipitous discovery demonstrating a greater cerebral cavernous malformation (CCM) burden within a murine CCM disease model housed in an unclean vivarium than in a cleaner facility led to the observation of intestinal microbiome involvement in CCM development through lipopolysaccharide from gram negative bacteria. Hence we investigated the effect on CCM development in CCM models by genetic or chemical disruption of the intestinal barrier.

Hypothesis:
Intestinal barrier disruption increases CCM burden in CCM murine models.

Methods:
Acute iBECre;

Ccm3
fl/fl

mice were bred to be deficient (

Muc2
+/-

,

Muc2
-/-

) in the mucin 2 gene with CCM assessment at P21. CCM burden was assessed in the following 3 chronic models at 5 months of age. The murine model

Ccm3
+/-

housed in an unclean vivarium was treated with 1% p80 emulsifier starting at 21 days of age (n=22) or with placebo (n=16). Less CCM penetrant

Ccm1
+/-

mice housed in a clean facility were contemporaneously treated with 2% dextran sodium sulfate (DSS) starting at 21 days of age (n=22) or with placebo (n=17). More CCM penetrant

Ccm1
+/-
Msh2
-/-

mice housed in an unclean vivarium were treated with 0.5% DSS starting at 2 months of age (n=11) or with placebo (n=6). We assessed CCM volume in brains by micro-computed tomography.

Results:
Mean CCM volume in acute

Ccm3
-/-

models doubled from 1.8 mm
3
with no
Muc2
loss (n=11) to 4.7 mm
3
with homozygotic
Muc2
loss (p<0.001, n=10) with an increasing trend to 2.6 mm
3
with heterozygotic
Muc2
loss (p=0.07, n=15). Mean CCM volume/brain volume (X 10
6
) per mouse doubled from 10.7 in placebos to 24.4 (p=0.01) by emulsifier treatment in the

Ccm3
+/-

chronic model and significantly increased from 0.1 in placebos to 9.2 (p<0.001) by 2% DSS treatment in the

Ccm1
+/-

model, with an increasing trend from 11.0 in placebos to 15.2 (p=0.086) by 0.5% DSS treatment in the

Ccm1
+/-
Msh2
-/-

model.

Conclusion:
CCM lesion development was enhanced by intestinal barrier disruption in 4 CCM models, regardless of the method used (genetic or chemical), time of onset, murine genotype or vivarium cleanliness status. Ongoing investigations include an early onset studies in the unclean vivarium with the

Ccm1
+/-
Msh2
-/-

mice receiving 0.5% DSS and the

Ccm3
+/-

mice receiving 2% DSS.
Abstract TMP11: Emergency Room Door-to-Puncture Time Since 2015: Observations From the BEST-MSU Study
Authors: Jagolino-Cole Amanda L , Czap Alexandra L , Parker Stephanie A , Yamal Jose-Miguel , Rajan Suja S , Bowry Ritvij , Sheth Sunil A , Hwang Hyunsoo , Singh Noopur , Bratina Patti , Bryndziar Tomas , Alexandrov Andrei , Alexandrov Anne W , Dusenbury Wendy , Swatzell Victoria , Jones William , Ackerson Kimberly , Schimpf Brandi , Wright Patrick , Grotta James C
Published: January 2019

Introduction:
The impact of a Mobile stroke unit (MSU) on access to Endovascular Thrombectomy (ET) is a pre-specified BEST-MSU sub-study. On the MSU, ET decision-making steps such as CT, neurologic exam, and tPA treatment are completed prior to Emergency Room (ER) arrival. We hypothesized that such pre-ER assessment of potential ET patients on a MSU improves metrics.

Methods:
BEST-MSU is a prospective comparative effectiveness study of MSU vs Standard Management by Emergency Medical Services (SM). We compared ER door-to-puncture-time (mins, DTPT) among the following groups of MSU and SM patients: all ET patients (ETP), ET patients post-tPA (ETT), and ET patients post-tPA meeting thrombolytic adjudication criteria (ETTA) over the first four years of the study.

Results:
There were 161 ETP (67 SM, 94 MSU), 140 ETT (55 SM, 85 MSU), and 126 ETTA (50 SM, 76 MSU) patients. DTPT was shorter for MSU patients (ETP 89 vs 99, p=0.01; ETT 93 vs 100, p=0.03; ETTA 93 vs 99.5, p=0.03). From 2015 to 2018, DTPT decreased at a faster rate for SM compared with MSU-managed patients, improving by about an hour (Figure).

Conclusion:
Pre-ER ET evaluation on a MSU results in faster DTPT. Since 2015, dramatic improvement in ER ET metrics has attenuated this difference. However, DTPT of 90-100 mins in all groups indicates substantial room for improvement.
Abstract TMP110: Design of the BP-COG Study of Blood Pressure Over the Life Course and Later-Life Cognition in Blacks, Hispanics, and Whites: A Pooled Cohort Analysis of ARIC, CARDIA, CHS, FOS, MESA, and NOMAS
Authors: Levine Deborah A , Gross Alden L. , Briceño Emily M. , Okullo Dolorence , Hingtgen Stephanie , Galecki Andrzej T. , Giordani Bruno J. , Sussman Jeremy B. , Hayward Rodney A. , Burke James F. , Kabeto Mohammed , Manly Jennifer J. , Elkind Mitchell S.V. , Kulick Erin , Gottesman Rebecca F. , Yano Yuichiro , Gaskin Darrell J. , Sidney Stephen , Roger Véronique L. , Allen Norrina Bai , Rogers Mary A. M
Published: January 2019

Background:
High blood pressure (BP), particularly in mid-life, increases the risk for late-life cognitive impairment and dementia (CID). The extent to which Blacks’ and Hispanics’ worse BP control starting in young adulthood contributes to their greater risk of CID compared to Whites is uncertain.

Objective:
To describe a pooled, multi-ethnic cohort created to determine the associations between BP levels over the life course and CID risk in Blacks, Hispanics, and Whites.

Methods:
We pooled individual-level data from 35,473 adults (22.6% Blacks, 8.1% Hispanics, 67.3% Whites, 2% Other) with baseline age ≥18 and cognitive assessments across 6 longitudinal cohorts in the United States from 1971 to 2016: Atherosclerosis Risk in Communities Study (ARIC), Coronary Artery Risk Development in Young Adults Study (CARDIA), Cardiovascular Health Study (CHS), Framingham Offspring Study (FOS), Multi-Ethnic Study of Atherosclerosis (MESA), and Northern Manhattan Study (NOMAS). We harmonized cognitive tests across studies into 3 factors representing global cognitive performance, executive function, and memory using statistically appropriate confirmatory factor analysis. Mean (SD) follow up was 17.1 (10.9) years.

Results:
The mean (SD) baseline age was 54.3 (16.4) years and 19554 (55.1%) participants were female (Table). There were 3193 (9.0%) first incident strokes (2651 ischemic, 348 hemorrhagic, and 117 other or undetermined type) and 15147 (42.7%) deaths. The Table presents mean BPs at the first and last visits by cohort and the pooled sample. From the initial to the last assessment, mean global cognition decreased over time (p<0.001), as did mean executive function (p<0.001) and mean memory scores (p<0.001) in the pooled sample.

Conclusion:
This will be the first comprehensive, large investigation of the association of BP levels from young adulthood to late-life and CID risk in Blacks, Hispanics, and Whites.
Abstract TMP13: NIH Stroke Scale Items Associated With Poor Outcomes in Patients 'Too Good To Treat' With IV Alteplase
Authors: Ali Syed F , Hemmen Thomas , Rost Natalia , Anderson Christopher , Etherton Mark , Schwamm Lee H
Published: January 2019

Introduction:
Prior reports showed poor outcomes in patients who did not receive IV tPA after acute ischemic stroke (AIS), due to mild or rapidly improving symptoms. (“too good to treat”, TGTT). Many factors have been associated with poor outcomes in this group of patients. We sought to evaluate individual NIHSS items associated with poor outcomes in these TGTT patients who didn’t receive thrombolysis.

Methods:
Using the GWTG stroke registry data from a large comprehensive stroke center in the Northeast, we analyzed 9,215 consecutive stroke admissions from 02/2002 - 04/2018 and identified patients who did not receive IV tPA due to TGTT. NIHSS items were grouped into Level of Consciousness (LOC), Language, Vision, Motor, Sensory and Coordination. Factors associated with poor outcome (defined as all discharge locations other than home) and in-hospital mortality were evaluated by univariate and multivariable regression with significance at p<0.05.

Results:
Of the 9, 215 analyzed patients, 444 (4.8%) didn’t received tPA due to being TGTT despite presenting within 4.5 hours of last know well. Patients with poor outcomes were more likely to be older, female, have a history of diabetes, atrial fibrillation, and present more often with deficits in level of consciousness, vision, motor, language and sensation. On multivariable analysis, age (OR 1.06, 95% CI (1.04, 1.08)), diabetes (OR 3.65, 95% CI (2.00, 6.71)), and deficits in LOC (OR 4.91, 95% CI (2.35, 10.24)) and strength (OR 4.65, 95% CI (2.79, 7.74)) were independently associated with poor outcome. Factors independently associated with in-hospital mortality were age, and deficits in LOC and strength.

Conclusion:
Half of all patients who did not receive thrombolysis due to TGTT in our sample had poor outcomes and 8.8% of those died in-hospital. Advanced age, and initial deficits in LOC and strength were strong predictors of a poor outcome. When present in milder strokes, these factors warrant careful consideration for tPA use.
Abstract TMP14: Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients With Recent Myocardial Infarction
Authors: Inohara Taku , Liang Li , Kosinski Andrzej , Smith Eric E , Schwamm Lee H , Hernandez Adrian F , Bhatt Deepak L , Fonarow Gregg C , Peterson Eric D , Xian Ying
Published: January 2019

Background:
Treatment with intravenous recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke (AIS) in patients with a recent history of myocardial infarction (MI) within 3 months prior to AIS is controversial.

Methods:
We used probabilistic linkage of Medicare claim files with the Get With The Guidelines-Stroke registry to identify patients who were treated with rtPA for AIS between 2/2009 and 12/2015. Recent MI was determined from Medicare claims. Multivariable logistic regression models were used to evaluate the association of a recent history of MI with in-hospital clinical outcomes.

Results:
Among 40,396 patients age 65 years or older treated with rtPA for AIS from 1522 sites (mean age [SD] 81.0 [8.1] years; 58.0% women), 241 (0.6%) had recent MI within 3 months prior to AIS, of which 19.5% were STEMI. Patients with recent MI had more severe stroke than those without (median NIHSS [IQR]: 13.0 [7.0-20.0] vs. 11.0 [6.0-18.0]) and were more likely to be on antiplatelets prior to AIS (87.8% vs. 53.6%). The unadjusted rates of in-hospital mortality and any serious rtPA-related complications were 17.4% and 13.5% for those with recent MI, and 9.0% and 9.4% for those without, respectively. Hemopericardium was observed in 1 (0.4%) patient with recent MI. After risk adjustment, recent MI within 3 months was associated with a significant increased risk of mortality (adjusted odds ratio [OR] 1.61, 95%CI [1.11-2.34], P=0.012), whereas there were no statistically significant differences in any serious rtPA-related complications (
Table
). When stratified by the type of MI, recent ST-elevation MI was associated with higher risk of death and tPA complications, but the difference was not statistically significant in those with recent non ST-elevation MI.

Conclusions:
Among older ischemic stroke patients treated with rtPA, recent MI within 3 months was associated with an increased risk of mortality, and recent STEMI with mortality and serious tPA complications.
Abstract TMP15: Thrombolysis in Stroke With Unknown Onset Based on Non-contrast Ct (TRUST CT). An International, Multicenter, Registry-based Study
Authors: Sykora Marek , Ferrari Julia , Krebs Stefan , Lang Wilfried , Michel Patrik , Eskandari Ashraf , Siarnik Pavel , Velika Barbora , Mengel Annerose , Poli Khouloud , Poli Sven
Published: January 2019

Background:
Thrombolysis in wake-up stroke (WUS) or stroke with unknown onset (SUO) has been recently proven to be safe and effective using magnetic resonance imaging (MRI). However, in most of the thrombolyzing hospitals worldwide MR imaging is not available. We hypothesize that pragmatic non-contrast CT (NCCT)-based WUS/SUO thrombolysis may be feasible and safe.

Methods:
TRUST-CT is an international multicenter registry-based study. WUS/SUO patients undergoing NCCT-based thrombolysis with NIHSS ≥ 4 and initial ASPECTS ≥ 7 are included and compared to propensity score matched non-thrombolyzed WUS/SUO controls. Primary endpoint is symptomatic intracranial hemorrhage (ICH); secondary endpoints include 24-hour NIHSS change of ≥ 4 and modified Rankin Score (mRS) at 90 days.

Results:
Until now 100 patients with NCCT-based WUS/SUO thrombolysis were included. As compared to 100 controls, the median admission NIHSS was 9 and 8, respectively; the median ASPECTS was 10 in both groups. 3 (3 %) patients and 0 controls suffered symptomatic ICH. A decrease of ≥ 4 NIHSS points was observed in 48 % of the thrombolyzed patients as compared to 25% in the control group (p = 0.001); 33% and 28% achieved mRS 0 to 1 at 90 days, respectively (p = 0.4).

Conclusions:
NCCT-based thrombolysis in WUS/SUO seems feasible, safe and eventually effective. Updated results will be presented and discussed in the context of current evidence.
Abstract TMP18: Intravenous Glibenclamide Reduces Hypoxanthine, a Novel Predictor of Brain Edema Formation: An Exploratory Analysis of GAMES-RP
Authors: Irvine Hannah J , Acharjee Animesh , Wolcott Zoe , Ament Zsuzsanna , Hinson Holly , Molyneaux Bradley J , Simard J Marc , Sheth Kevin N , Kimberly W Taylor
Published: January 2019

Introduction:
To further characterize the effects of intravenous (IV) glibenclamide (glyburide; BIIB093) therapy on brain edema, we studied patients enrolled in the phase 2 GAMES-RP trial. We performed metabolomic analysis on serial blood samples to examine the relationship between treatment, plasma metabolites, and matrix metalloproteinase-9 (MMP-9) and midline shift (MLS).

Methods:
Metabolite profiling was performed on 399 serial plasma samples from the modified intention-to-treat GAMES-RP cohort (N=83). Blood samples were subjected to liquid chromatography-tandem mass spectrometry to measure 181 analytes. MMP-9 levels and MLS were measured as part of the original trial. Logistic regression was used to identify metabolites affected by IV glibenclamide treatment and repeated measures mixed effects models were used to examine association with MMP-9 and MLS. A decision tree-based machine learning algorithm, Random Forest (RF), was used to further verify leading candidates. Mediation analysis was performed to evaluate for metabolite mediators of IV glibenclamide’s effect on MMP-9 and MLS.

Results:
IV glibenclamide reduced plasma hypoxanthine level relative to treatment with placebo (24.7% reduction,
p
=0.003). Hypoxanthine was associated with increased MMP-9 level (
β
=1.76,
p
=5.2x10
-18
) and greater MLS (
β
=0.081,
p
=2.8x10
-4
). Multivariable analyses demonstrated these associations to be independent of age, gender, baseline NIHSS, DWI lesion volume, and tPA treatment. RF analysis confirmed hypoxanthine as a leading predictor of IV glibenclamide treatment, MMP9 and MLS. Hypoxanthine was a partial mediator of the effect of glibenclamide on MLS (22% mediation, Sobel test statistic -2.4,
p
=0.017) and a full mediator of MMP-9 (53% mediation, Sobel test statistic -2.6,
p
=0.009).

Conclusion:
Hypoxanthine was associated with increased MMP-9 and MLS, and was reduced by treatment with IV glibenclamide. As a biomarker implicated in free radical generation and blood-brain barrier breakdown after ischemia, hypoxanthine may be related to the effect of IV glibenclamide in preventing edema after ischemic stroke.
Abstract TMP2: BP Matters: In Hospital Blood Pressure Predicts Poor Outcomes Following Mechanical Thrombectomy for Large Vessel Occlusion Strokes
Authors: McCarthy David , Ayodele Maranatha , Luther Evan , Bryant Jean Paul , Kimball John , Elwardany Omar , Shienberg Dallas , Starke Robert
Published: January 2019

Introduction:
For patients with large vessel occlusions (LVOs), current data focuses on strict blood pressure (BP) management 24 hours post-mechanical thrombectomy (MT). We assessed the longitudinal relationship between in-hospital BP following MT and outcomes.

Methods:
We reviewed our prospectively maintained database of consecutive patients with LVO treated with MT from 2016 to 2017. Daily maximum systolic (SBP) and diastolic blood pressures were recorded. Relationships between maximum BP values and mortality, hemorrhage, and functional outcome (FI=mRS≤2) at follow up were analyzed in a multivariable logistic regression analysis. Longitudinal BP trends with regards to outcome was analyzed with repeated measures ANOVA.

Results:
A total of 228 thrombectomies were performed. Incremental 10 mmHg increases in peak 24-hour SBP were independently predictive of a higher likelihood of hemorrhagic conversion (OR 1.2, p=0.017) and a trend towards decreased functional outcome (OR 0.86, p=0.06). Independent of hemorrhage and additional covariates, incremental 10 mmHg increases in day 3 peak SBP was strongly correlated with worse functional outcomes (OR, 0.66 p=.0001). Day 3 SBP>140 was independently predictive of a lower likelihood of favorable outcome (OR 0.35, p=0.006). Between 24 and 48 hours post-MT, all patients demonstrated a decrease in peak SBP. Patients with functional dependence on follow up (mRS>2) had a rebound in peak SBP 48-72 hours post-MT (mean SBP change: FI -3.5 mmHg, non-FI +3.9 mmHg; p=.005; figure 1). This trend more pronounced in patients without hemorrhage (mean SBP change: FI -3.1 mmHg, non-FI +5.9 mmHg; p=.003).

Conclusion:
High maximum SBP and a rebound SBP on the third day following MT is independently associated with worse functional recovery.
Abstract TMP32: Post-Stroke Systemic Inflammation: Immunomodulation by Progesterone and Vitamin D Hormone
Authors: Atif Fahim , Yousuf Seema , Harris Wayne A , Espinosa-Garcia Claudia , Stein Donald G
Published: January 2019

Introduction:
Post-stroke systemic inflammation due to in-hospital infections increases patient morbidity and mortality. We examined the immunomodulatory effects of progesterone (P4) either alone or in combination with vitamin D hormone (VDH) on post-stroke systemic inflammation-induced peripheral immune dysfunction and functional deficits.

Methods:
Adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion/reperfusion (tMCAO) or sham surgery. Delayed systemic inflammation was induced by injections of lipopolysaccharide (LPS; 50 μg/kg; IP) at 24, 28 and 32 h post-occlusion. P4 (8 mg/kg; IP) and VDH (1 μg/kg; IP) were given 5 min prior to reperfusion followed by SC injections on days 1, 2 and 3 post-stroke. Power analysis specified a sample size of 6 rats/group to detect a 30% difference between treatment groups with a power of 80% at alpha 0.05. There were 6 groups (n=6/gp): 1) Sham + vehicle (SHAM); 2) tMCAO + vehicle (VEH); 3) tMCAO + vehicle + LPS (VEH + LPS); 4) tMCAO + LPS + P4 (P4); 5) tMCAO + LPS + VDH (VDH); 6) tMCAO + LPS + P4 + VDH (P4 + VDH). At day 4 post-stroke, rats were tested on spontaneous locomotor activity, grip strength and sensory neglect; peripheral immune dysfunctions were assessed by flow cytometric analysis of subsets of immune cells in blood, spleen and thymus. We measured markers of neuronal inflammation (GFAP, Iba-1, IL-6), apoptosis (cleaved caspase-3, TUNEL), and endoplasmic reticulum (ER) stress (PERK, eIF2α, CHOP) in brain. Data were analyzed using ANOVA with the Tukey-HSD
post hoc
test. Statistical significance was set at
p
<0.05.

Results:
The worst stroke outcomes were seen in the VEH + LPS group. Peripheral immune dysfunctions revealed by flow cytometry were significantly (
p
<0.05) restored by both P4 and VDH monotherapy. While P4 and VDH individually improved functional deficits, neuronal inflammation, apoptosis and ER stress induced by post-stroke systemic inflammation, the
combination
of P4 + VDH improved outcomes significantly (
p
<0.05) more than monotherapy.

Conclusions:
Our findings may have translational relevance because the current standard of care for stroke and post-stroke infections is largely ineffective and our P4+VDH combination therapy may hold promise for stroke therapeutics.
Abstract TMP40: Secondary Motor Nerve Deficit Correlates With Poorer Outcome in Acute Stroke Patients
Authors: Liao Songjie , Lai Chongyuan , Yu Jian
Published: January 2019

Introduction:
Anterograde degeneration after stroke leads to secondary injury of peripheral motor nerves. It remains unclear whether this secondary dysfunction affects functional improvement and whether early electrophysiological parameters could possibly predict rehabilitative outcome.

Methods:
A total of 43 adult patients of middle cerebral artery infarction (MCAI) within 2 weeks after onset was prospectively recruited from January 2016 to December 2017. Ten healthy subjects were recruited as control. All the subjects were investigated by electromyography to record and analyze electrophysiological parameters on admission. All the patients were evaluated by NIHSS, BI, mRS, Fugl-Meyer assessment (FMA) and Alberta Stroke Program Early CT score on admission, then by BI, mRS and FMA in the 6-month follow-up. Multiple regression analysis was used to screen the possible predictive factor for neurological outcome.

Results:
Twenty-six patients were with massive MCAI and 17 patients with subcortical MCAI. The compound muscle action potential (CMAP) amplitude of median, ulnar, tibial and common peroneal nerves, and motor unit number estimation in abductor of pollicis brevis were significant decreased in the hemiplegic limbs than those in the unaffected limbs and in the healthy controls, and further diminished in massive MCAI compared to those in subcortical MCAI. Fibrillation potentials / positive sharp waves in abductor digiti minimi and tibialis anterior were found in majority of patients, and were more frequently detected in massive MCAI, confirming the motor axonal deficit. CMAP amplitude of the affected ulnar nerves was significantly decreased in patients with unfavorable outcome (mRS>3) 3 and 6 months after attack, shown as an independent predictor for poorer outcome. In addition, the affected ulnar CMAP ≥10.45mV was associated with more than 50% decrement of mRS 6 months post stroke, with sensitivity and specificity of nearly 80%.

Conclusions:
The data indicated that secondary peripheral motor deficit occurred within 2 weeks after stroke, correlated with severity of the disease. Relatively low CMAP amplitude of hemiplegic ulnar nerve could serve as an independent factor to predict poorer outcome and worse recovery in the 6-month follow-up.
Abstract TMP46: EEG is a Useful Biomarker of Motor Recovery in Early Stroke Rehabilitation
Authors: Cassidy Jessica M , Kaur Kiranjot , Masuda Ashley K , Srinivasan Ramesh , Cramer Steven C
Published: January 2019

Introduction:
The application of biomarkers to study and monitor stroke recovery mechanisms can potentially advance rehabilitation practice and research. This study examined the utility of dense-array electroencephalography (EEG) for predicting and capturing changes in brain function in early stroke rehabilitation.

Hypothesis:
Changes in EEG measures involving ipsi- and contralesional motor cortices (iM1 and cM1) in delta (1-3Hz) and high beta (20-30Hz) frequency bands [1] parallel and [2] predict motor recovery.

Methods:
Individuals with recent ischemic or hemorrhagic stroke admitted to an inpatient rehabilitation facility (IRF) completed a 3-minute resting-state EEG recording and behavioral testing (Upper Extremity Fugl-Meyer (FM) and Functional Independence Measurement motor subscale (FIM-motor)) during hospitalization and 90-days post-stroke. EEG power and coherence (connectivity) measures were computed from leads overlying iM1 and cM1.

Results:
Twenty-seven subjects (20 males, age 58.3±14.6 years, 14.7±12.8 days post-stroke) participated. Greater decrease in iM1-cM1 coherence in the delta band correlated significantly with larger (a) FIM-motor score improvement from IRF admission to discharge (r=-0.70, p=0.001, n=18) and (b) FM score improvement from IRF admission to 90-days post-stroke (r=-0.57, p=0.02, n=17). Baseline EEG measures did not predict motor recovery when examined across the entire group. Performance of biomarkers varies according to stroke severity, and so prediction was further examined in relation to baseline FM. In subjects with moderate-severe impairment (FM≤40), delta iM1-cM1 coherence at baseline correlated with FIM-motor gains (r=0.72, p=0.03, n=9), and delta power in leads over iM1 positively correlated with FM gains (a) from IRF admission to discharge (r=0.75, p=0.03, n=8) and (b) from IRF admission to 90-days post-stroke (r=0.73, p=0.04, n=8).

Conclusions:
Bedside EEG recording in the IRF provides neurophysiological insights that predict and parallel motor recovery, and so may be a valuable bedside tool in early stroke rehabilitation. EEG measures can predict motor recovery in individuals with moderate-severe motor impairment.
Abstract TMP50: Racial Differences in Mechanical Thrombectomy Among Patients With Ischemic Stroke
Authors: Esenwa Charles , Lekoubou Alain , Bishu Kinfe , Ovbiagele Bruce
Published: January 2019

Introduction:
Despite decades of national declines in stroke incidence, African Americans (AA) are 2-3 times more likely to have a stroke, are younger at the time of their stroke and are more likely to die of a stroke, when compared to Non-Hispanic Whites (NHW). This likely related to differing risk factor profiles and decreased access to care. We sought to describe the recent trends in national and regional thrombectomy utilization and determine if there are racial disparities in treatment of large vessel occlusion.

Methods:
The National Inpatient Sample (NIS) approximates a 20% stratified sample of all hospital discharges in the US. We queried the NIS from 2006-2014 stroke, tPA administration and endovascular thrombectomy. We stratified utilization by race (AA, Hispanic, NHW and other) and accounted for sex, age, hospital characteristics, US region, household income, insurance type, tPA, disease severity and other factors using logistic regression.

Results:
We identified a total of 889,309 observations of acute stroke, of which there were 5,256 thrombectomy observations (0.60%). Overall thrombectomy utilization nearly quadrupled from 2006-2008 to 2014-2016 (OR 3.6, CI 2.50-5.10). In the adjusted model, rate of thrombectomy utilization was significantly lower for AA compared to NHW (OR 0.67, CI 0.58-0.76) but not for Hispanics (OR 0.94, CI 0.78-1.13). Utilization rates by US region (Northeast, Midwest, South, West) were only significant for increased utilization in the US West (OR 1.57, CI 1.15-2.07). Utilization rates did not differ by income quartiles, but varied by insurance type with Medicaid associated with a lower odds (OR 0.87, CI 0.76-1.00) and private insurance a higher odds (OR 1.24, CI 1.14-1.34) of thrombectomy utilization. Interaction analysis of AA race and insurance type was not significant.

Conclusions:
We show show a significant disparity in thrombectomy utilization for AA compared to NHW. More work is needed to understand the underlying drivers.
Abstract TMP62: Emergency Triage to Predict Collaterals in Acute Ischemic Stroke: Imaging Bests Clinical Factors in the STRATIS Registry
Authors: Liebeskind David S , Mueller-Kronast Nils H , Aziz-Sultan M. Ali , Froehler Michael T , Klucznik Richard P , Saver Jeffrey L , Sanossian Nerses , Zaidat Osama O , Hellinger Frank R , Yavagal Dileep R , Yao Tom L , Nogueira Raul G , Jahan Reza , Haussen Diogo C ,   for the STRATIS Investigators
Published: January 2019

Background:
Collateral grade is an established determinant of outcomes in acute ischemic stroke (AIS). The triage, workflow and therapeutic options for AIS may be tailored to collaterals and identifying key predictors of collateral status may therefore be crucial. We hypothesized that degree of collateral circulation prior to endovascular therapy in AIS may be predicted at the time of initial patient evaluation and triage.

Methods:
The STRATIS Registry showed that timelines, technical, and functional outcomes could be effectively attained in a large real-world cohort of endovascular therapy. Baseline clinical and imaging predictors of core lab adjudicated collateral grade (ASITN) by conventional angiography were determined, using multivariate modeling.

Results:
586 STRATIS subjects (67.5 ± 15.2 years, 52.7% male) presenting with AIS at 147.4 ± 101.8 min from symptom onset (TFSO) and median NIHSS score 17.0 (range 8.0,30.0) were analyzed. Collateral grade was poor (ASITN 0-1) in 81, moderate (ASITN 2) in 297 and good (ASITN 3-4) in 208. Baseline stroke severity inversely correlated with collaterals (NIHSS per point, OR 0.946, 0.916-0.977, p=0.001), yet no clinical variables such as age, sex or co-morbidities were predictive of collateral status. Less severe ASPECTS at imaging triage (median 9, range 2-10) was associated with better collateral grade (ASITN 0-1, median 7 (2-10); ASITN 2, 8 (3-10); ASITN 3-4, 9 (5-10), p<0.001) and the strongest predictor of collaterals during triage (per point, OR 1.608, 1.399-1.849, p<0.001). Interestingly, the predictive nature of ASPECTS was not modified by TFSO (p=NS). Specific ASPECTS regions (all cortical M1-M6, but no subcortical) affected by early ischemia were also predictive of collateral grade. In particular, insular ASPECTS changes at imaging triage was the strongest predictor of collateral grade (ASITN 0-1, 53/66 (80.3%); ASITN 2, 139/258 (53.9%); ASITN 3-4, 41/194 (21.1%), p<0.001).

Conclusions:
Imaging, using only ASPECTS, during triage strongly predicts collateral grade, irrespective of time from symptom onset. Clinical variables, however, may not be used to accurately predict collaterals in the real-world practice of endovascular therapy.
Abstract TMP67: Prehospital Screening for Large Vessel Occlusion and Bypass to Endovascular Stroke Centers: Using the Ambulance Clinical Triage for Acute Stroke Treatment Scale With Adaptation From DAWN and DEFUSE-3 Trials
Authors: Ogle Kyle L
Published: January 2019

Background and Purpose:
The Ambulance Clinical Triage for Acute Stroke Treatment (ACT-FAST) scale uses two steps for large vessel occlusion (LVO) identification and a third step for transfer eligibility to endovascular-capable stroke centers. The purpose of this study was to modify the last step of ACT-FAST prehospital screening tool to include patients with a last known well < 24 hours, and compare it with other existing stroke scales that are solely used to predict LVO.

Methods:
Patients with a final diagnosis of acute ischemic stroke who had a completed NIHSS score in the emergency department of my hospital between February 2017 and June 2018 were retrospectively investigated. Presence of LVO was determined by angiography imaging and/or physician diagnosis. The steps of the ACT-FAST scale used for LVO identification were compared with other current stroke prediction scales that utilize optimal cut-off scores. The third step of the ACT-FAST scale was modified for inclusion of patients with last known well time of < 24 hours, and evaluated for ability to triage patients to endovascular-capable stroke centers.

Results:
101 consecutive acute ischemic stroke patients, with an ED NIHSS score documented, were identified between February 2017 and June 2018. Of these 101 patients, 21 had a proximal LVO. The first two steps of the ACT-FAST scale to identify LVO had a higher accuracy compared to 3ISS ≥ 4, LAMS ≥ 4, CPSS =3, and PASS ≥ 2. The modified 3-step ACT-FAST showed 0.97 accuracy in ability to correctly triage patients to endovascular-capable stroke centers.

Conclusions:
The first 2 steps of the ACT-FAST scale showed superiority in this study for identifying LVO with less steps compared to other existing scales. The modified 3-step ACT-FAST scale showed high accuracy for appropriately recognizing endovascular-eligible patients. Further validation of the modified ACT-FAST scale is recommended with use of prospective studies within the field to determine patient benefit.
Abstract TMP68: Simple Neurological Exam Combined With Headpulse Accurately Predicts Large Vessel Occlusion Stroke
Authors: Keenan Kevin J , Lovoi Paul A , Smith Wade S
Published: January 2019

Introduction:
Early prediction of whether or not a patient is having a large vessel occlusion (LVO) stroke could facilitate faster treatment through triage to an endovascular center. Clinical LVO stroke prediction scales achieve accuracies near 80%. We developed a non-invasive device to measure the Headpulse (imperceptible head movements due to the cardiac contraction detected by cranial accelerometry) and used this biometric data and a stroke scale to predict LVO.

Methods:
Academic hospital emergency department and transfer code stroke patients had a 3-minute Headpulse recording after CTA and prior to thrombectomy when applicable. Intracranial hemorrhage patients were excluded. We quantified the variance of Headpulse recordings from one cardiac cycle to the next and used supervised machine learning (MATLAB Classification Learner R2018a) with 5-fold cross validation to train a model. This was repeated after adding the SAVE scale (1 point for each of Speech abnormality, asymmetric Arm weakness, Vision deficit, Eye deviation). Patients were classified as LVO if there was an occlusion of the ICA, M1, M2, vertebral, or basilar arteries on CTA or non-LVO if the CTA was normal or showed only more distal occlusion(s).

Results:
42 patients were included. Of 18 LVO patients there were 3 ICA, 1 basilar, 10 M1, and 4 M2 occlusions. Of 24 non-LVO patients there were 11 ischemic strokes, 2 TIAs, and 11 stroke mimics.

Adding SAVE to the training data resulted in a classification tree with 'asymmetric arm weakness' as the first node due to its high accuracy. Subsequent Headpulse nodes led to correct classification of all patients that would be false positives by clinical exam alone.

Conclusions:
In a highly selected derivation cohort, clinical exam correctly classified LVO patients 93% of the time. Addition of a biometric derived from cranial accelerometry improved this accuracy. Validation in a representative code stroke cohort with intracranial hemorrhage patients is required.
Abstract TMP71: The Los Angeles Motor Scale - Atrial Fibrillation (LAMS-AF) Score is Superior to LAMS in Predicting Large Vessel Occlusion
Authors: Narwal Priya , Chang Andrew , Mac Grory Brian , Jayaraman Mahesh , McTaggart Ryan , Paolucci Gino , Cutting Shawna , Burton Tina , Dakay Katarina , Schomer Ashley , Noorian Ali Reza , Nour May , Liebeskind David , Saver Jeffrey , Furie Karen , Yaghi Shadi
Published: January 2019

Background:
There is evidence that suggests that a LAMS >/= 4 is a good predictor of LVO and this threshold is oftentimes used to triage stroke patients in the field to the nearest comprehensive stroke center. In this study, we aim to determine whether atrial fibrillation (AF) can improve the ability of LAMS in predicting LVO.

Methods:
We included consecutive patients with a diagnosis of ischemic stroke admitted within 24 hours from last known normal time who underwent emergent vascular imaging using a computerized tomography angiography (CTA) of the head and neck. LVO was defined as intracranial internal carotid artery, proximal middle cerebral artery (M1 or proximal M2 segment), or basilar occlusion. We defined atrial fibrillation (AF) as history of AF or telemetry in the emergency department showing AF. The LAMS score was determined in the ED upon arrival. Univariate and multivariable models were performed to identify predictors of LVO and to determine whether AF improves the ability of LAMS to predict LVO.

Results:
Among 1234 patients admitted to our institution within the study period, 862 underwent emergent vascular imaging (69.8%) out of which 374 (43.4%) had evidence of LVO and 207 (24%) underwent mechanical thrombectomy. After adjusting for confounders, independent predictors of LVO were LAMS (adjusted OR 1.42 per one point increase 95% CI 1.29-1.57) and AF (OR 1.95 95% CI 1.26-3.02, p<0.001) (Table 2). We developed the LAMS-AF that includes the LAMS score and adds 2 points if AF is present. In this analysis, LAMS-AF (AUC 0.78) was superior to LAMS (AUC 0.76) in predicting LVO (Figure). Results remained unchanged when thrombectomy was used as outcome. Using LAMS-AF lead to re-classification of 8/68 patients (11.8%) in the LAMS=3 group into the high-risk LVO group (Table 3)

Conclusion:
In patients with LAMS=3, using the LAMS-AF score may improve the ability of LAMS in predicting LVO. More studies are needed to confirm our findings particularly using field LAMS.
Abstract TMP84: Demographic and Geographic Variation in 5-year Survival after Acute Ischemic Stroke among Medicare Population Cohort, 2007-2015
Authors: Tong Xin , Chang Anping , Shieb Linda , George Mary G , Gillespie Cathleen , Merritt Robert , Yang Quanhe
Published: January 2019

Introduction:
Little is known about demographic and geographic differences in long-term survival among older patients with acute ischemic stroke (AIS).

Methods:
We included 923,876 Medicare fee-for-service beneficiaries ≥65 years of age diagnosed with AIS from 2007 to 2010. The overall survival was defined as time from date of AIS to date of death, or through last follow-up date of 12/31/2015. We used a Cox proportional hazard model to obtain age, sex, race, and poverty level adjusted survival estimates.

Results:
Among 923,876 Medicare beneficiaries hospitalized with AIS in 2007-2010, we documented 606,540 deaths (65.7%) during a median of 4.2 years follow-up through 2015, representing 3.88 million person years. The overall adjusted 5-year survival was 45%; beneficiaries aged 65-74 years had 65% survival at 5-years, 46% for those 75-84 years, and 19% for those ≥85 years. Non-Hispanic blacks had significantly lower overall survival as compared to Non-Hispanic whites (adjusted 5-year survival 41% vs. 46%, p<0.001). There were differences in 5-year survival patterns by state, from 50% (South and North Dakota) to 41.7% (Hawaii). The states in the stroke belt region (Arkansas, Georgia, Tennessee, North Carolina, Kentucky, Louisiana, and Mississippi) had lower 5-year survival after stroke (range 42.5% - 43.8%).

Conclusion:
Significant demographic and geographic differences in 5-year survival after AIS were identified among 2007-2010 Medicare beneficiaries. Further study is needed to examine factors associated with these findings and develop prevention strategies to enhance survival.
Abstract TMP91: Increased Blood Pressure Variability in the SPS3 Trial is Associated With Recurrent Stroke
Authors: de Havenon Adam , Tirschwell David , Stoddard Greg , Majersik Jennifer , Rost Natalia
Published: January 2019

Introduction:
Hypertension is the leading cause of small-vessel stroke; however, mechanisms of stroke related to blood pressure variability (BPV) are not well understood.

Hypothesis:
Greater BPV will be correlated with increased ischemic stroke recurrence in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.

Methods:
All blood pressures in the 30 days after randomization were excluded to reduce confounding from the study intervention. The study exposure was BPV, defined as standard deviation (SD) and coefficient of variation of the systolic blood pressure, during days 30-365 of SPS3. Cox proportional hazards regression was used to calculate hazard ratios relating BPV to stroke events during the remainder of study follow-up. Patients were excluded if they had stroke during the exposure period.

Results:
This analysis included 2,764 patients, 157 (5.7%) of whom developed stroke. Mean±SD follow-up was 1091±699 days and number of blood pressure readings per patient was 39±14. The SD was higher in patients who developed recurrent stroke (Table 1). A 10 mm Hg shift in SD was associated with a hazard ratio of 1.53 for stroke (Table 2). This association was not affected by SPS3 blood pressure treatment arm.

Conclusion:
Greater BPV was associated with a minor increase in the risk of recurrent stroke in SPS3. Additional research is needed to understand the causal mechanism and methods to reduce BPV.
Abstract TP105: Investigation of S-nitrosoglutathione in Stroke: A Systematic Review of Literature in Pre-Clinical and Clinical Research
Authors: Liu Shimeng , Lowe Forrest , Yu Wengui , Zheng Haiqing , Singh Inderjit , Feng Wuwei
Published: January 2019

Background:
S-Nitrosoglutathione (GSNO) is a nitric oxide donor that that has been investigated for neuroprotective and neuro-recovery effect. We aimed to conduct a systematic review on the published literature using GSNO in both human and animal stroke studies.

Methods:
We searched PubMed up to June 30, 2018, using the following keywords: S-Nitrosoglutathione, GSNO, stroke, cerebrovascular, carotid arteries, middle cerebral artery, and MCA. Only studies published in the English language providing efficacy results of GSNO on ischemic stroke were included. STAIR Score was used for the quality assessment of preclinical studies and PEDro Score was used to evaluate clinical trials. A meta-analysis was conducted to compare the effect size.

Results:
Of 39 articles identified, 10 (6 for preclinical and 4 for clinical studies) met eligibility criteria and were included (Fig. 1a). Meta-analysis was done for the 4 clinical studies. The median STAIR Score across the preclinical studies was 5.5 (range: 4-7)(Fig.1b) and the PEDro Score for the 4 clinical trials ranged from 6 to 10 (Fig.1c). Among the included 6 preclinical studies, 5 studies found that GSNO reduced infarct size, while 4 studies demonstrated improved neurological behavior (Fig.1d). Inverse-variance weighted linear meta-analysis of standardized mean difference (Hedge’s g) on 4 human studies revealed a big effect size (Hedge’s g=-0.82, 95% CI: [-1.26, -0.38], P=0.0003) favoring the GSNO group in term of reducing embolic signals (Fig. 1e&1f).

Conclusions:
There are positive signs from both preclinical and clinical studies that GSNO has potential application in human strokes.