bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 177: Exploratory Results From the B01-02 Trial: Administration of MultiStem® Results in Decreased Circulating CD3+ Cells and Lower Levels of Inflammatory Cytokines
Authors: Clark Wayne M , Devlin Thomas G , Yavagal Dileep R , Sen Souvik , Bernstein Richard A , Wechsler Lawrence R , Chiu David , Hess David C ,   B01-02 Investigators, Lang Brad , Mays Robert W
Published: July 2021

Introduction:
B01-02 was a double-blind, placebo-controlled study of ischemic stroke patients (NIHSS 8-20, inclusive) treated within 24-48 hours of symptom onset with MultiStem, an adult, adherent, stem cell product. In pre-clinical models of stroke, MultiStem appears to confer improved neurological benefit through multiple mechanisms, including down-regulation of the peripheral immune response. We sought to determine whether this observation translated to acute ischemic stroke patients treated with MultiStem.

Methods:
Patients were randomized 1:1 and received IV infusion of 1.2 billion cells or placebo. After randomization, patients had blood drawn to determine baseline levels of circulating levels of CD3+ cells or specific inflammatory cytokines. Blood was drawn again at days 2, 7 and 30 post-treatment to determine the average fold change from baseline in each patient at each time point.

Results:
126 patients formed the Intention-To-Treat (ITT) population, 65 receiving MultiStem, 61 placebo. 38 MultiStem patients and 40 placebo patient samples were analyzed for CD3+ cells, while 60 MultiStem patients and 55 placebo patients samples were analyzed for serum cytokine levels. CD3+ cell levels were significantly decreased in the MultiStem treatment group compared to placebo (p=0.001) at Day 2, but not later. IL-6 (p=.031) and IL-12 (p=.035) were both significantly downregulated in the MultiStem treatment group at Day 7. IL-1β (p=.065), TNF-α (p=.068) and IFN-γ (p=.100) also trended towards being significantly reduced at Day 7.

Conclusions:
IV administration of MultiStem within 24-48 hours of an ischemic stroke results in decreased circulating CD3+ cells, while reducing inflammatory cytokines in the blood during the first 7 days after onset of symptoms. These results support the hypothesis that MultiStem treatment limits the activation of the innate immune system’s response to stroke, which may provide improved neurological and recovery outcomes. Additional studies are required to confirm this observation and optimize the time of administration for MultiStem mediated benefit
Abstract 184: Relationship Between Hospital Mortality and Readmission for Patients Hospitalized With Ischemic Stroke
Authors: Lichtman Judith H , Leifheit-Limson Erica , Wang Yun , Goldstein Larry B
Published: July 2021

Background:
CMS publically reports hospitals’ 30-day, all-cause, risk-standardized mortality (RSMR) and readmission (RSRR) rates for several conditions and plans to use similar metrics for ischemic stroke. Although an inverse relationship in these measures (i.e., hospitals with lower mortality rates being more likely to have higher readmission rates) has not been found for acute cardiovascular disease or pneumonia, data for stroke have not been similarly analyzed. We determined whether there is an association between hospital 30-day RSMRs and RSRRs for ischemic stroke, accounting for heterogeneity across the healthcare communities in which patients receive care (i.e., hospital referral regions).

Methods:
We used data from CMS Hospital Compare to determine hospitals’ 30-day RSMRs and RSRRs for 2010-2013 and assessed their relationship using Pearson correlation. We then fit a mixed model with a random intercept for hospital referral region, using RSRR as the dependent variable, RSMR as the independent variable, adjustment for hospital characteristics, and weighting by hospital volume.

Results:
There were 2,639 hospitals with 491,105 stroke discharges during the study period. The US national 30-day RSMR was 15.3% and the RSRR was 13.4%. There was a negative relationship between the 30-day RSMRs and RSRRs (r=-0.12; p<0.001) that remained after adjustment for hospital characteristics (point estimate -0.08, 95% CI -0.06 to -0.11). This association was no longer significant after accounting for variation across hospital referral regions (point estimate -0.01; 95% CI -0.04 to 0.02).

Conclusion:
Unlike acute cardiovascular disease and pneumonia, there was an inverse relationship between hospitals’ RSMRs and RSRRs for ischemic stroke. The absence of this relationship after accounting for hospital referral region suggests that heterogeneity of available health services between communities plays an important role in post-discharge stroke patient outcomes.
Abstract 192: Mechano-growth Factor (MGF) and Cerebral Vasospasm (CV) Post Aneurysmal Subarachnoid Hemorrhage (aSAH)
Authors: Przybycien-Szymanska Magdalena M , Rackohn Todd M , Yang Yuchen , Ashley William W
Published: July 2021

Cerebral vasospasm (CV) and related ischemic injury is a major contributor to death and disability after aneurysmal subarachnoid hemorrhage (aSAH). Our overall goal is to understand molecular mechanisms of action of endogenous mechano-growth factor (MGF), a splice variant of insulin-like growth factor 1 (IGF-1), in the brain. MGF was found to be neuroprotective after stroke in a gerbil model of ischemic injury and may serve as a potential therapeutic target to prevent CV-induced brain damage. In our studies, we characterized hypoxia induced changes in MGF expression in different brain regions, commonly affected by CV, at different time points (from 2 hours to 7 days) post 4h hypoxia treatments (6, 8,10 or 12% oxygen). The brain regions analyzed were motor cortex, hippocampus, striatum and hypothalamus. In addition, we characterized changes in MGF expression in microparticle (MP) fractions isolated from cerebrospinal fluid (CSF) extracted from CV patients. Microparticle fractions were isolated from CSF samples using serial ultracentrifugation. We used real time RT-PCR, western blots, and enzyme immunosorbent assay to quantify changes in gene expression and protein levels.

In the animal model, our results showed that there were time, dose and brain region specific changes in MGF expression that correlated with changes in the expression of heme oxygenase 1 (HO-1) and biliverdin reductase A, which are molecules involved in neuroprotection, and caspases, apoptotic markers. These results suggest that changes in endogenous MGF due to hypoxia may activate neuroprotective pathways in the brain. In CSF MPs isolated from CV patients, we observed an increase in MGF expression that correlated with the CV onset window and with an increase in HO-1, suggesting that similar pathways are activated post-CV in humans and post-hypoxia in animals. These data indicate that endogenous MGF may play a role in CV onset and may be a neuroprotective target in CV papteins. However, further studies are required to elucidate the molecular mechanisms of MGF and its exact role in CV development and patient outcome.
Abstract 203: Acute Kidney Injury in Acute Ischemic Stroke Patients Receiving Endovascular Treatment: Analysis of the Interventional Management of Stroke (IMS) - III
Authors: Herial Nabeel A , Saleem Muhammad A , Miran Muhammad Shah , Qureshi Adnan I
Published: July 2021

Background:
Endovascular treatment involves cerebral angiography with injection of contrast agents that are nephrotoxic and carry risk of renal failure. Our objective was to determine the incidence and identify predictors associated with acute kidney injury in ischemic stroke patients undergoing endovascular treatment.

Materials and methods:
Data from the Interventional Management of Stroke (IMS) - III clinical trial was utilized in which acute ischemic stroke patients were randomized into endovascular or intravenous treatment groups. Baseline and day 5 or discharge serum creatinine levels along with the demographic and comorbidity information was collected. Acute Kidney Injury classification was used to ascertain severity of renal dysfunction and based on increase in Day 5 creatinine levels from baseline, stage 1 (1.5 to 2 fold), stage 2 (>2 to 3 fold), and stage 3 renal failure (>3 fold increase from baseline) were identified.

Results:
Total of 434 patients received ET and 222 patients received intravenous treatment (IVT) with tissue plasminogen activator (tPA). Increase in serum creatinine levels was observed in 52 patients (12%) receiving ET and 24 patients (11%) in the IVT group. Renal failure (stage 1 or higher) was observed in 5 patients (1.2%) in the ET group and 3 patients (1.4%) in the IVT group. In univariate analysis, only age was associated with higher incidence of renal failure in the ET group. No significant association was observed with comorbid diagnoses, particularly pre-existing hypertension or diabetes mellitus. Baseline creatinine level was associated with renal failure (p=0.029) in patients receiving ET and pre-existing diagnosis of renal disorders was associated with renal failure in patients receiving IVT.

Conclusions:
In the IMS III data, incidence of acute kidney injury in acute ischemic stroke was low and was not different from patients receiving IVT.
Abstract 35: Transfusion Relieves Cerebral Metabolic Stress in Children with Sickle Cell Disease
Authors: Guilliams Kristin P , Fields Melanie E , Ragan Dustin K , Eldeniz Cihat , Binkley Michael , McKinstry Robert C , Shimony Joshua S , Vo Katie D , Wang Danny J , Hulbert Monica L , An Hongyu , Lee Jin-Moo , Ford Andria L
Published: July 2021

Introduction:
Transfusions (Tx) are the mainstay of stroke prevention in children with sickle cell disease (SCD), but the pathophysiology conferring this neuroprotection is not well understood.

Hypothesis:
Tx relieves cerebral metabolic stress by improving arterial oxygen content, thereby lowering chronically-elevated cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in children with SCD at risk for stroke.

Methods:
Children with SCD on chronic Tx therapy underwent two brain MRIs with measurement of CBF via pseudocontinuuous arterial spin labeling and OEF via asymmetric spin echo sequence within 24 hours of exchange Tx. To determine how Tx may reduce regions of elevated OEF, we set absolute OEF thresholds (45, 47.5, 50%) and compared tissue volumes above each threshold pre- and post-Tx using nonparametric paired statistics.

Results:
Twelve children with SCD (6-21 yrs) underwent MRIs. Tx raised Hb and lowered CBF and OEF (Figure), suggesting that elevated CBF and OEF may be markers of metabolic stress relieved by Tx. While CBF correlates with age in healthy children, pre-Tx CBF correlation with age was lost (τ= -0.42, p=0.07), but regained post-Tx (τ= -0.76, p=0.001). Also, absolute change in OEF diminished with increasing age (τ=. -0.75, p=0.003). Regions with very high OEF were found in the periventricular white matter, a common area of infarcts in SCD (Figure, average OEF maps pre- and post-Tx). Tx reduced the volume of these brain regions defined by all three OEF thresholds (Table), suggesting that Tx reduces brain regions at high risk for stroke.

Conclusion:
Tx in SCD children improves arterial oxygen content by increasing Hb, allowing CBF and OEF to fall, thus relieving metabolic stress globally and regionally. The absolute change in OEF correlates with age, suggesting that the efficacy of Tx may be age-dependent.
Abstract 50: Evaluation of Candidate Polymorphisms for Association With Brain Arteriovenous Malformations and Intracranial Hemorrhage in Hereditary Hemorrhagic Telangiectasia
Authors: Pawlikowska Ludmila , Nelson Jeffrey , Guo Diana E , McCulloch Charles E , Lawton Michael T , Kim Helen , Faughnan Marie E ,   Brain Vascular Malformation Consortium HHT Investigator Group
Published: July 2021

Introduction:
Brain arteriovenous malformations (AVM) are an important cause of intracranial hemorrhage (ICH) in young adults. Most are sporadic, but also occur in inherited diseases such as hereditary hemorrhagic telangiectasia (HHT). ICH presentation of brain AVM in both sporadic and HHT cases is a marker of high ICH risk. In order to investigate whether the same genetic modifiers influence sporadic and HHT brain AVM, we evaluated candidate genetic polymorphisms reported as associated with sporadic brain AVM, with ICH presentation or ICH during clinical course, in HHT patients.

Methods:
We genotyped 8 polymorphisms (
APOE
E2/3/4 [rs7412, rs429358],
ANGPTL
rs116724,
EPHB4
rs314308,
IL6
-174G>C [rs1800795],
IL1B
-31T>C [rs1143627],
ITGB8
rs10486391,
TNF
-238G>A[rs361525]) in 753 Caucasian HHT patients enrolled by the Brian Vascular Malformation Consortium (BVMC). Genotypes were collapsed into risk allele carriers vs. other for analysis, as published for sporadic AVM.
APOE
E2/3/4 haplotypes were assigned based on genotypes of the 2
APOE
polymorphisms. Association of genotype with phenotype was evaluated by multivariable logistic regression adjusted for age, gender and accounting for family clustering. We used a nominal significance threshold of p=0.05, requiring the same direction of effect as in sporadic brain AVM (odds ratio for risk genotype [OR]>1).

Results:
Among 753 HHT patients, 155 (21%) had brain AVM, of whom 26 (17%) presented with ICH. Two additional brain AVM patients had ICH during follow-up. None of the 7 variants (6 single nucleotide polymorphisms and
APOE
haplotype) were significantly associated with brain AVM (OR=0.6-1.3), with ICH presentation of brain AVM (OR=0.4-1.9), or with any brain AVM ICH in HHT patients (OR=0.5-2.1).

Conclusions:
Common genetic variants previously reported to be associated with sporadic brain AVM were not associated with brain AVM nor with ICH in the BVMC HHT cohort, suggesting different genetic modifiers may influence sporadic and HHT brain AVM. However, the number of ICH cases in the cohort is small, so the confidence intervals are wide and we cannot rule out clinically important associations. The BVMC is enrolling additional HHT patients to expand the cohort and increase power for association analyses.
Abstract 64: Perlecan LG3 is Neuroprotective When Administered Intra-arterially After Experimental Ischemic Stroke
Authors: Salmeron Kathleen , Maniskas Michael , Fraser Justin , Bix Gregory
Published: July 2021

Despite recent advances in stroke therapy, stroke remains a leading cause of morbidity and mortality. We have previously demonstrated the therapeutic potential of exploiting the brain’s endogenous protection and repair processes following stroke. Specifically, we reported that the LG3 protein fragment of the heparan sulfate proteoglycan perlecan is neuroprotective and proangiogenic in vitro. We now hypothesize that LG3 could be therapeutic in experimental stroke. However, as previous in vivo LG3 studies suggest that it may not readily target stroke-affected brain upon systemic administration, we administered LG3 in a super selective intra-arterial (IA) model (into the ipsilateral common carotid artery) following transient (1 hour) middle cerebral artery occlusion in 3 month old male mice. Upon reperfusion the mice received LG3 or vehicle controls via IP (5 mg/kg) or IA (0.15 mg/kg) administration. No differences in vital signs were noted between the treatment groups. We observed that all LG3 treated mice, regardless of route of administration, had a smaller infarct compared to controls on post-stroke day 3. Importantly, those mice that received IA LG3 had much smaller strokes and performed significantly better in forced movement and in free movement settings than all other treatment conditions. Our results demonstrate that acute LG3 administration is beneficial after experimental ischemic stroke, IA LG3 is safe and much more effective than IP, and support further investigation of LG3 as a novel acute stroke therapy.
Abstract 72: A Novel VLSM-CST Lesion Load Model is a Superior Predictor of Motor Outcomes of Acute Stroke Patients
Authors: Wang Jasmine , Feng Wayne , Chhatbar Pratik Y , Schlaug Gottfried
Published: July 2021

Introduction:
Lesion load of the Corticospinal Tract (CST-LL) can predict 64% of the variance in 3-months outcome of acute stroke patients. Voxel-based lesion symptom mapping (VLSM) studies have revealed brain voxels associated with motor impairment. A combined VLSM- CST-LL approach may give particular weight to voxels that are both part of an impairment map and the descending motor tracts.

Hypothesis:
A combined VLSM-wCST-LL model can predict acute motor outcome better than weighted CST-LL alone.

Methods:
We derived the VLSM map from a group of 50 chronic patients with variable motor deficits relating voxels of patients’ lesions to Upper Extremity Fugl-Meyer (UE-FM) scores. A correction for multiple comparisons was applied at FDR<0.05. Resulting VLSM T-maps were multiplied using our probabilistic CST maps, and then summed to form a canonical VLSM-weighted CST tract. Individual lesion maps from 76 acute stroke patients were overlaid onto the VLSM-weighted CST map to calculate lesion load. Patients were assessed for motor impairment (UE-FM) at baseline and at 3 months. Linear regressions were fit for baseline UE-FM, wCST-LL, and Days-of-Therapy (DoT) to determine predictions of 3-months outcome. A multivariate regression was run using VSLM-weighted CST-LL, controlling for baseline UE-FM and DoT. Age was not a significant regressor. Akaike Information Criterion was run to select the best fit model.

Results:
The VLSM analysis determined that voxels of lesions in the precentral gyrus, premotor regions, the corona radiata region, and within the descending motor tracts were significantly related to chronic motor impairment. VLSM-CST-LL applied to a group of acute stroke patients with motor impairment predicted 85% of the variance at 3 months motor outcome. AIC results confirmed with 99% certainty that VLSM is the best fit model.

Conclusions:
VLSM-weighted CST-LL is the superior fit model compared to the weighted CST-LL model for predicting 3 months outcome.
Abstract 96: Neuroimaging Markers of Small Vessel Disease Differ Between Types of Recent Small Subcortical Infarcts
Authors: Arsava Ethem Murat , Acar Bilgehan , Kaplan Berkan , Gocmen Rahsan , Topcuoglu Mehmet Akif
Published: July 2021

Background:
The current neuroimaging standards of small vessel disease favor classification of all patients with a recent infarction in the territory of one perforating artery under the umbrella term of recent small subcortical infarcts (RSSI). Nonetheless the pathophysiology of perforator artery stroke is heterogeneous (microatheroma formation, lipohyalinosis or embolism), which is reflected by different infarct patterns on imaging studies. In this study, our aim was to determine whether chronic imaging markers of small vessel disease vary among patients with different imaging features of RSSI.

Methods:
Features of small vessel disease (lacunes, microbleeds, perivascular spaces, white matter hyperintensities) were rated and small vessel disease burden score was determined in a consecutive series of 242 ischemic stroke patients admitted with RSSI. Small subcortical infarcts were dichotomized into proximal and distal patterns based on their proximity to the parent artery. Radiological and clinical features were compared among these groups by univariate and multivariate analyses.

Results:
The cardiovascular risk factor profiles were similar between both groups. Patients with proximal pattern (n=63) more likely had an alternate stroke etiology other than small artery occlusion, like cardioembolism or proximal large vessel atherosclerosis (p=0.03). On radiologic evaluation, chronic lacune (p=0.03), microbleed (p=0.05) and periventricular white matter hyperintensity (p=0.04) burden, as well as the burden score (p=0.05) was significantly higher among patients with distal pattern. Multivariate analyses, which took into account the effect of age and cardiovascular risk factors, showed a significant association between higher small vessel burden score and the distal small subcortical infarction pattern (p<0.01).

Conclusion:
There is significant heterogeneity among patients with RSSI with respect to neuroimaging markers of small vessel disease. These markers, together with lesion patterns, might prove to be useful in accurately identifying different subgroups of RSSI, which would be critical in understanding of the relevant pathopysiology and development of appropriate treatment strategies.
Abstract NS5: Improvement of Follow-up Rate After Discharge of Acute Ischemic Stroke Patients by the Man-to-man Education for Stroke During Admission
Authors: Yu Hee Sun , Yun Na Young , Shin Jong Wook , Jeong Hye Seon , Yoo Sangeun , Nam Hye Suk , Kim Jei
Published: July 2021

Background:
We have executed a man-to-man stroke education program for acute ischemic stroke patients during admission since 2012. The contents of the man-to-man stroke education includes warning signs of stroke, guidance for prompt actions after symptom onset, drug information, and exercise and nutrition behavior after discharge. We evaluated whether the man-to-man education given during admission is effective to improve follow-up rates after discharge for acute ischemic stroke patients.

Methods:
We compared clinical data including modified Rankin Scale (mRS) at discharge and length of stay and follow-up data after discharge of 697 acute ischemic stroke patients (Male:Female=283:414, mean age±SD, 69.0±12.1 years) admitted in 2013, who received the man-to-man education during admission, with the data of 602 patients (M:F=254:348, 67.1±12.2 years) admitted in 2008, who did not receive the active education during admission.

To evaluate follow-up rates, we first checked the follow-up status of all included patients within 1, 4, 8, 12, 16 months after discharge. Then, follow-up rates at each time point were calculated as the ratio of the number of patients followed at the point to the all patients discharged in 2008 or 2013. Differences of the follow-up rates between 2008 and 2013 were compared at individual follow-up time points using one-sided x2-test.

Results:
Even though the favorable outcome defined as 0-3 of mRS at discharge was similar between 2008 and 2013 (2008 vs. 2013, 88.3 vs. 87.4%, p=0.342), length of admission was significantly shorter in 2013 than 2008 (2008 vs. 2013, 10.2 vs. 6.6 days, p<0.001). On follow-up rates evaluations, follow-up at 1 month was significantly higher in 2013 (89.8%) than 2008 patients (83.7%) (p=0.001). The follow-up rates subsequently decreased at 4months (2008 vs. 2013, 77.3 vs. 81.5%, p=0.040), 8 months (70.1 vs. 74.3%, p=0.051), 12 months (63.1vs. 67.6%, p=0.052), and 16 months (57.6 vs. 63.0%, p=0.028). However, the follow-up rates of 2013 patients was consistently higher than 2008 ones.

Conclusion:
The present data suggested that active education program for acute ischemic stroke patients could improve to follow-up rates of the patients after discharge.
Abstract TMP10: A Retrospective Comparison of Medical Eligibility for Acute Ischemic Stroke Clinical Trials Compared with Hospital Enrollment Rates: Greater Cincinnati/Northern Kentucky Population
Authors: Kleindorfer Dawn , Moomaw Charles J , Khoury Jane , Alwell Kathleen , Saver Jeffrey L , Khatri Pooja , Adeoye Opeolu , Broderick Joseph P , Flaherty Matthew L , Brott Thomas G , Spilker Judith , Schmit Pamela , Woo Daniel , De Los Rios La Rosa Felipe , Mackey Jason , Martini Sharyl , Ferioli Simona , Kissela Brett M
Published: July 2021

Introduction:
Low rates of enrollment into stroke clinical trials are an ongoing challenge for the stroke research community. We sought to retrospectively describe the association between medical eligibility and recruitment rates for two acute clinical trials.

Methods:
Within a population of 1.3 million, we screened local hospital admissions in 2010 using ICD-9 discharge codes 430-436, and performed chart review. Within the region are 15 adult acute care hospitals, all of which are covered by the same stroke team for clinical care and trial enrollment. Medical eligibility, the number of eligible patients/total number of patients, was calculated for the IMS-III trial and the CLEAR-ER trials using their inclusion/exclusion criteria. The number of patients enrolled in the trial per month of open enrollment was determined for each hospital. Statistical analysis included paired signed rank test and regression.

Results:
In 2010, 2035 ischemic strokes (IS) were hospitalized in the region. Regional medical eligibility was 1.7% for IMS III and 4.5% for CLEARER (p=0.001), overall regional hospital enrollment/month was 0.81 for IMS III and 1.84 for CLEAR-ER (p=0.001). Eligibility rates per hospital ranged from 0-9.5%, and recruitment rates per hospital/mo ranged from 0-0.38. Hospital-level eligibility and recruitment rates were significantly correlated (see figure for both trials combined, adjusted r2 = 0.57, p<0.001.)

Discussion:
Within our population, medical eligibility explained 57% of the variability in hospital-level enrollment rates for two acute IS trials. The use of population-based epidemiology in trial planning may identify optimal trial enrollment criteria, which must be weighed against proper patient selection. Many other factors impact enrollment rates, such as competing trials, which were not considered here. Further evaluation of our population-based eligibility rates in sites outside our region and with additional clinical trials is needed.
Abstract TMP105: Endovascular Treatment of Severe and Refractory Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage Improves Outcome: A Systematic Review and Meta-analysis of Different Treatment Options Evaluated Since 2006 for Cerebral Vasospasm
Authors: Boulouis Gregoire , Labeyrie Marc-Antoine , Raymond Jean , Rodriguez-Regent Christine , Lukaszewicz Anne-Claire , Bresson Damien , Ben Hassen Wagih , Trystram Denis , Meder Jean-Francois , Oppenheim Catherine , Naggara Olivier
Published: July 2021

Introduction:
To report clinical outcome of aneurysmal subarachnoid hemorrhage (aSAH) patients exposed to cerebral vasospasm (CVS) targeted treatments in a systematic review and meta-analysis and compare the efficacy of endovascular and non-endovascular treatments in severe / refractory vasospasm patients.

Methods:
The literature was searched using PubMed, EMBASE, and The Cochrane Library database. Eligibility criteria were (1) Rated clinical outcome; (2) at least 10 patients; (3) aSAH; (4) study published in English or French (January 2006 - October 2014); and (5) methodological quality score > 10, according to STROBE criteria. Endpoint included unfavorable outcome rate, defined as mRS 3-6, GOS 1-3 or GOSE 1-4 at latest follow-up. Analyses included stratification per route of administration (oral, i.v., intra-arterial or cisternoventricular) and per study inclusion criteria (severe, CVS, refractory CVS or high risk for CVS). Univariate and multivariate subgroup analyses were performed to identify interventions associated with a better outcome.

Results:
Sixty-two studies, including 26 randomized controlled trials, were included (8976 patients). Overall 2490 patients had unfavorable outcome including death (random-effect weighted average: 33.7%, 99%CI, 28.1-39.7%; Q-value: 806.0, I
2
=92.7%). Clinical outcome was significantly better in severe or refractory patients for whom, on top of best medical treatment, endovascular intervention was performed (RR=0.76, IC95% [0.66-0.89], p <0.00001) whereas other route of administration didn’t show significant differences. RR of unfavorable outcome was significantly lower, vs control groups, in patients treated with Cilostazol (RR=0.46 (IC99% [0.25-0.85], P = 0.001, Q value 1.5, I
2
= 0).

Conclusion:
In case of CVS following aSAH, endovascular treatment in severe / refractory vasospasm patients. including intra-arterial injection of pharmacological agents or balloon angioplasty, improves outcome as compared to other route of administration.
Abstract TMP109: Bidirectional Influence Between Vascular β-amyloid and Tau: An Experimental Evidence
Authors: Ihara Masafumi , Saito Satoshi , Hattori Yorito , Yamamoto Yumi , Nagatsuka Kazuyuki
Published: July 2021

Background and Purpose:
Cerebral amyloid angiopathy (CAA) is a putative substrate of vascular cognitive impairment and is frequently observed in Alzheimer’s disease (AD) in addition to parenchymal β-amyloid (Aβ) plaques and neurofibrillary tau tangles. Several studies using amyloid precursor protein (APP) and microtubule-associated protein tau (MAPT) bigenic mice showed enhanced neurofibrillary degeneration without any alterations in Aβ plaques, indicating that tau is downstream of Aβ. However, interaction between CAA and tau still remains unknown.

Methods:
We have developed a double transgenic mouse by crossing mice overexpressing the human APP gene with Swedish-Dutch-Iowa mutations (Tg-SwDI mice) with Tg-P301S mice carrying the human MAPT gene with P301S mutation to investigate the role of CAA in tau metabolism.

Results:
Immunohistochemical staining showed that the amount of total tau, 4 repeat tau, and hyperphosphorylated tau was more abundant in the double Tg mice than Tg-P301S mice. The double Tg mice showed most prominent tau accumulation in the subiculum where vascular Aβ deposition first appears in Tg-SwDI mice while they exhibited significantly increased vascular Aβ deposition in the dentate gyrus where tau accumulation is marked in Tg-P301S mice. The Aβ deposits were composed of Aβ40 and mainly observed in the capillaries. The double Tg mice showed more pronounced astrogliosis, microgliosis, and neuronal loss than wild type mice or single Tg mice with the greatest reduction of cerebral blood flow in cortex based on laser speckle flowmetry and significantly impaired spatial reference memory in the Barnes maze test.

Conclusions:
These findings indicate bidirectional influence between vascular Aβ and tau, suggesting a positive feedforward loop of toxic protein accumulation. Thus, CAA plays a key role in development of dementia, both of vascular and neurodegenerative origin.
Abstract TMP113: Long-term Cognitive Decline After Intracerebral Hemorrhage
Authors: Biffi Alessandro , Anderson Christopher D , Ayres Alison M , Greenberg Steven M , Rosand Jonathan , Viswanathan Anand
Published: July 2021

Introduction:
Cerebral small vessel disease (CSVD) is the leading cause of Vascular Cognitive Impairment (VCI). Although Intracerebral Hemorrhage (ICH) is the most severe manifestation of CSVD, VCI among ICH survivors has been the subject of limited investigations.

Hypothesis:
We sought to test these hypotheses: 1) long-term cognitive decline rates are substantial even among initially non-demented ICH survivors; 2) underlying CSVD plays a substantial role in determining post-ICH long-term cognitive decline.

Methods:
We enrolled survivors of primary ICH, with no evidence of dementia 6 months post-hemorrhage, in a single-center longitudinal observational study. Presence and severity of CSVD was assessed at enrollment using two established markers of CSVD on CT (CT-defined white hatter hypodensity [CT-WMH]) and MRI (cerebral microbleeds [CMBs]). We captured blood pressure measurements during follow-up via review of medical records. Cognitive performance was assessed using the Modified Telephone Interview for Cognitive Status (TICS-m), a standardized validated telephone-based cognitive battery. We constructed multivariate models of cognitive decline rate, defined as slope of TICS-m scores over time.

Results:
A total of 275 ICH survivors qualified for inclusion in our analyses; of these 83 (30%) developed incident dementia and 33 (12%) developed incident Mild Cognitive Impairment (MCI) at 5 years (Figure). CSVD imaging markers were associated with cognitive decline rate (CT-WMH: p=0.001, CMBs: p=0.003), as were pulse pressure (p=0.003) and systolic blood pressure variation coefficient (p=0.034).

Conclusions:
Long-term cognitive decline is frequent and substantial among ICH survivors not demented at time of ICH, and strongly associates with severity of underlying CSVD. Our findings suggest that it is the extent of CSVD and not particular ICH characteristics that are most associated with long-term cognitive decline in survivors of ICH.
Abstract TMP114: Cerebral Ischemia Combined With Amyloid Angiopathy Significantly Deteriorated Cognitive Impairment via Angiotensin AT1 Receptor in a Mouse Model of Alzheimer’s Disease
Authors: Nakagawa Takashi , Hasegawa Yu , Mitsuyama Shokei K
Published: July 2021

Introduction:
Ischemic stroke is suggested to be potentially associated with cognitive impairment in Alzheimer’s disease. Recent clinical data suggest that treatment with angiotensin receptor blocker (ARB) is associated with less incidence of Alzheimer’s disease than other classes of antihypertensive drugs. However, it is unknown whether cerebral ischemia can indeed trigger cognitive decline in Alzheimer’s disease and whether ARB can exert beneficial effect on ischemia-induced cognitive decline.

Hypothesis:
We hypothesized that cerebral ischemia deteriorates cognitive impairment in Alzheimer’s disease, through angiotensin II.

Methods and results:
We used 5XFAD mouse, a model of Alzheimer’s disease with vascular and cerebral amyloid-β(Aβ) deposition. Transient cerebral ischemia of mice was induced by bilateral common carotid artery occlusion (BCCAO) for 17 minutes. The post-treatment with olmesartan, an ARB, or vehicle was started at 24 hours after BCCAO, and was performed for 5 weeks. Mice were divided into 5 groups: (1) wild type, (2) wild type with BCCAO, (3) 5XFAD, (4) 5XFAD with BCCAO, (5) 5XFAD with BCCAO and olmesartan administration, to evaluate cognitive impairment. BCCAO in 5XFAD caused greater escape latency (p<0.01) on Water maze test (reference-/working-memory) and greater migration distance (p<0.05) on Open field test than that in wild type, indicating that cerebral ischemia combined with Aβ deposition enhanced cognitive decline. Post-treatment with olmesartan significantly reduced escape latency (p<0.01) on Water maze test, retention trial latency (p<0.05) on Passive avoidance test, and retention time of outer zone (p<0.01) on Open field test in 5XFAD subjected to BCCAO. BCCAO significantly deteriorated cognitive impairment, and this protection against BCCAO by olmesartan was associated with the protection of neuron in hippocampus and the suppression of blood-brain barrier disruption. Furthermore, olmesartan significantly attenuated brain oxidative stress, and NADPH oxidase subunits P67 in 5XFAD.

Conclusion:
We first demonstrated that cerebral ischemia combined with amyloid angiopathy markedly deteriorates cognitive impairment in 5XFAD mouse, through AT1 receptor.
Abstract TMP2: Is Eptifibatide a Viable and Safe Option as Stand-alone Therapy for Acute Ischemic Stroke Patients?
Authors: Korya Daniel , Moussavi Mohammad , Mehta Siddhart , Brar Jaskiran , Chahal Harina , Daniels Josh , Samaan Mena , Panezai Spozhmy , Kirmani Jawad
Published: July 2021

Introduction:
The list of contraindications for IV tPA in acute ischemic stroke (AIS) is often too long and may lead to physicians opting to offer no treatment for certain strokes. An alternative treatment is proposed in cases where IV tPA is not an option due to time-window restrictions or contraindications. We compared the stroke severity, outcomes and safety of IV eptifibatide when compared with IV tPA.

Methods:
Patients who presented to a community based university affiliated comprehensive stroke center from 2012-15 with AIS over a two-year period were included in the study. Those who qualified for IV tPA, and were treated, were compared with patients who only received IV eptifibatide. The initial NIH Stroke Score (NIHSS), 24-hour NIHSS, discharge NIHSS (DCNIHSS), discharge mRS (DCmRS) and symptomatic ICH rates were compared with a paired samples t-test to determine significance of difference between the means. SPSS Version 22 was used for all data analysis.

Results:
A total of 864 patients presented with AIS in the evaluated time period and of those 166 met study criteria. There were 119 patients who received IV tPA alone (group A) and 47 patients received eptifibatide (group B). The mean initial NIHSS, 24-NIHSS, DCNIHSS, DCmRS and percent bleeding complications for group A were: 11.2, 10.8, 8.6, 3.1 and 6%. For group B the figures were: 6.7, 4.8, 4.3, 1.7 and 0%, respectively. Group A was compared with group B in a paired samples T-test and yielded -4.3, -6.2, -6, -1.5 (p=.0001 to .04) for initial, 24-hour, discharge NIHSS and discharge mRS, respectively. The difference between initial and discharge NIHSS between the two groups was -2.7 (p=.009), favoring IV tPA.

Conclusion:
In patients who are either outside the time-window or with contraindications to IV tPA, eptifibatide may be a safe alternative and appears to be efficacious. None of the patients who were started on eptifibatide had bleeding complications and they had a statistically significant improvement in their level of disability and stroke severity at discharge. A limitation of this study is that patients in group A had significantly worse initial NIHSS compared with group B. To better evaluate the efficacy of eptifibatide, a larger, prospective study should be initiated.
Abstract TMP24: Duration of Asymptomatic Status and Outcomes Following Endarterectomy and Stenting in the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST)
Authors: Moore Wesley S , Voeks Jenifer H , Roubin Gary S , Clark Wayne M , Howard Virginia J , Jones Michael R , Brott Thomas G ,   for the CREST Investigators
Published: July 2021

Introduction:
Inclusion of asymptomatic patients in randomized trials comparing revascularization to medical therapy has been questioned if they have been previously symptomatic.

Hypothesis:
Duration of asymptomatic status is not associated with better outcomes following endarterectomy (CEA) or stenting (CAS).

Methods:
Patients in CREST were classified as asymptomatic if they had not had a TIA or stroke ipsilateral to the study artery within 6 months prior to randomization. We compared those patients who had always been asymptomatic (AA) to those who had been previously symptomatic (PS) ≥ 6 months prior to randomization. Proportional hazards models adjusting for age and treatment were used to assess risk of 30-day stroke or death (S+D), and risk of any 30-day S+D plus ipsilateral stroke at 4 years by asymptomatic status

Results:
Among the 1056 asymptomatic patients who received the assigned procedure within 30 days of randomization, 977 (93%) were AA and 79 (7%) were PS. There was no difference in the 30-day and 4 year outcomes (Table).

Conclusion:
In CREST, 93% of the asymptomatic patients were always asymptomatic. Similar outcomes for the previously symptomatic patients (7%) supports the inclusion of such patients in randomized trials comparing CEA and CAS to medical treatment.
Abstract TMP37: Physicians’ Preferences in the Management of Silent Stroke: Results From a Worldwide Survey
Authors: Crump Lauren , Li Yue , Sharma Mike , Sacco Ralph L , Smith Eric E ,   on behalf of the Stroke Outcomes Rsch Canada Working Group (SORCan-www.sorcan.ca), Saposnik Gustavo
Published: July 2021

Introduction:
Patients with silent cerebral infarction (SCI) or microbleeds (MB) are at higher risk of developing a recurrent vascular event or suffering a hemorrhage as a consequence of thrombolysis or antithrombotic treatment. Additionally, the presence of occult cerebrovascular lesions on imaging may alter therapeutic or diagnostic recommendations. However, clinical guidelines are lacking.

Hypothesis:
We hypothesize that a wide variability in physician diagnostic and treatment preferences exist for individuals with SCI and MB.

Methods:
Respondents were practicing neurologists with expertise in stroke care identified from WSO, CSC, Vas-Cog and SORCan. Those who agreed to participate were sent a questionnaire which was completed online. Participants randomly received 10 cases from a pool of 20, assessing perception of risk for later stroke and treatment preferences, as well as demographic questions.

Results:
Among the 252 participants, 35 (13.9%) were excluded for incomplete responses. Of 217 participants included in this analysis, two thirds of participants would proceed with revascularization therapies (tPA: 40%, endovascular: 8%, combined: 22%) for a case scenario with acute global aphasia (NIHSS 6-7) and remote bilateral MB. Additionally, physicians would order an echocardiogram regardless of the location of the SCI (cortical SCI: 56%, lacunar SCI: 44%; p>0.05). In a case-scenario with mild hypertension and 4 deep microbleeds presented with difficulty with balance, almost half of respondents did not recommend antiplatelet drugs or statins (40.2%), and 20% recommended both antiplatelet and statins. NOACS were the most commonly recommended antithrombotic treatment in a case-scenario with atrial fibrillation (AF), SCI, and a remote lobar intracerebral hemorrhage (46.4%), followed by aspirin (20.9%), no treatment (17.3%).

Conclusion:
There is a wide variability in the management of SCI and MB among stroke experts. The present study highlights the need for further research in treatment efficacy, as well as recommendations from scientific organizations to guide clinicians in the management of high risk patients with SCI and MB.
Abstract TMP56: Mapping the Dynamics of Brain Perfusion During and Following Transient Middle Cerebral Artery Occlusion (tMCAo) in the Rat Using Functional Ultrasound (fUS)
Authors: Baron Jean-Claude , Brunner Clement , Isabel Clothilde , Martin Abraham , Dussaux Clara , Savoye Anne , Emmrich Julius V , Montaldo Gabriel , Mas Jean-Louis , Urban Alan
Published: July 2021

Introduction:
Following MCAo, tissue outcome varies depending on depth and duration of hypoperfusion and efficiency of reperfusion. However, the precise time-course of these events in relation to tissue and behavioral outcome remains unsettled due to lack of a wide field-of-view quantitative imaging technique able to map perfusion in the rodent brain at high spatiotemporal resolution. Here we used fUS, a novel approach to map cerebral blood volume (CBV) without contrast agent.

Hypothesis:
fUS will allow quantitative, near real-time mapping of CVB during and after tMCAo.

Methods:
45min filament tMCAo was induced in adult SD rats; sham rats were also used. fUS was used to map the penetrating arterioles and venules of the ipsi- and contra-lateral motor (M1-2) and somatosensory (S1) cortex in coronal sections across the MCA territory at 80μm resolution. Three-min coronal scans were taken at different levels before, during and immediately after MCAo, and at 3 and 6 days thanks to a thinned-skull preparation. CBV was expressed relative to mirror ROI. In addition, a 1-hr movie (one frame/5s) was taken starting a few mins after reperfusion. Serial Neuroscore and 2 sensorimotor tasks were given over 3w post-MCAo, and then NeuN, IBa1 and GFAP immunofluorescence (IF) at post-mortem.

Results:
fUS showed a ∼80% CBV reduction in S1 during occlusion (p<0.001; n=7), with partial (∼60%, p<0.001) return of CBV on reperfusion, followed by a full return at days 3 and 6. As expected for this model, similar but less conspicuous CBV changes prevailed in M1-2. Continuous reperfusion was depicted in 5/7 rats (slope range: 8-25%/hr relative to prior CBV), but not in 2 rats. There were no significant changes in behavior relative to the sham group (n=4), and IF showed no infarction but marked selective neuronal loss (SNL) in the striatum in 5/7 rats and milder cortical SNL in 4/7 rats.

Conclusions:
fUS efficiently mapped the acute changes in CBV during occlusion and following reperfusion with high spatio-temporal resolution, allowing the charting of fine tissue reperfusion dynamics in the individual rat. fUS is ideal to longitudinally map real-time cerebral perfusion in experimental stroke from the hyper-acute through to the chronic stage.
Abstract TMP61: Outcomes After Ischemic Stroke Among “America’s Best Hospitals”
Authors: Lichtman Judith H , Leifheit-Limson Erica , Wang Yun , Goldstein Larry B
Published: July 2021

Background:
The ranking of “America’s Best Hospitals” by the US News & World Report is a popular hospital-profiling system, but it is not known whether the 50 top hospitals for Neurology and Neurosurgery have lower 30-day risk-standardized mortality (RSMR) and readmission rates (RSRRs) after stroke compared with other hospitals, or whether outcomes are comparable among these 50 top hospitals.

Methods:
The 50 top hospitals for adult Neurology and Neurosurgery were identified from the 2015-16 US News & World Report rankings. CMS Hospital Compare provided RSMRs and RSRRs within 30 days of ischemic stroke for hospitals with ≥25 stroke cases/year. We fit a mixed model to assess differences in RSMRs and RSRRs between top-ranked vs other hospitals, adjusted for hospital characteristics and weighted by hospital volume. Among the 50 top-ranked hospitals, we explored whether ranking order was associated with outcomes.

Results:
Among 2718 hospitals, the 50 top-ranked vs other hospitals had lower mean 30-day mortality (RSMR 14.8% vs 15.3%, p<.01) but higher readmission (RSRR 14.5% vs 13.4%, p<.01). These patterns persisted in adjusted analyses; top hospitals had lower mortality by 0.98% (95% CI -1.36%, -0.60%) and higher readmission by 0.66% (0.41%, 0.92%). Among top hospitals, there was considerable variability in risk-standardized outcomes, ranging from 9.5-19.3% for mortality and 10.8-17.5% for readmission. RSMRs were lower than the national average for 14% of top hospitals while RSRRs were lower for only 2% and higher for 14% (figure). Hospital rank was not significantly associated with either mortality (RSMR 0.04% increase with each rank, 95% CI 0.0%, 0.08%) or readmission (RSRR -0.01%; 95% CI -0.04%, 0.02%) among the 50 top-ranked hospitals.

Conclusions:
Admission to a top-ranked hospital for Neurology or Neurosurgery was associated with lower 30-day risk-standardized mortality but higher readmission. There was considerable heterogeneity among the top 50 hospitals.