bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP433: Subcortical Stroke in E4FAD Transgenic Mice Modulates Amyloid Plaque Accumulation, Motor Recovery After Stroke, and Memory Dysfunction
Authors: Huang Julia , Teng Edmond , Cole Gregory , Hinman Jason
Published: June 2021

Introduction:
Cerebral microvascular disease and Alzheimer’s disease (AD) account for the majority of dementia diagnoses with 50% of patients having mixed dementia with features of both microvascular stroke in the white matter and AD pathology. This significant co-morbidity indicates an interactive neurobiologic relationship yet it is unclear if these two pathologies synergize or simply co-exist.

Methods:
To determine the synergistic effect of subcortical stroke on amyloid deposition, focal subcortical white matter ischemic lesion underneath left sensorimotor cortex or sham procedures were introduced at 2 months of age into E4FAD transgenic mice that express the human ApoE4 knock-in allele together with the 5xFAD transgene or littermate controls. Animals underwent behavioral assessment, brain metabolism analysis by PET/CT, and histologic tissue analysis.

Results:
In E4FAD-positive mice, subcortical stroke vs. sham resulted in a greater inter-hemispheric difference in amyloid burden in the ipsilateral hemisphere (-0.291 vs. -0.078, p=0.08). This was associated with improved motor recovery on rotarod testing in the E4FAD-positive plus stroke group compared to E4FAD-negative stroke group (53.8 sec vs. 45.23 sec, p=0.016). In E4FAD-positive mice, subcortical stroke vs. sham also resulted in improved hippocampal memory function on fear conditioning (17.6+/-5.0 vs. 32.9+/-5.0, p=0.082) while hippocampal plaque number was not significantly different in this cohort.
18
F-FDG PET/CT imaging demonstrated reduced frontal cortex metabolism in the mixed dementia cohort.

Conclusions:
This novel mouse model of mixed subcortical stroke and Alzheimer’s disease in E4FAD mice illustrates the value of studying the overlap between vascular and Alzheimer’s pathology in the biology of these two common disorders. The combined pathologies demonstrate a potentially paradoxical enhancement in motor recovery and memory impairment compared to stroke or Alzheimer’s disease alone, suggesting that activation of unique molecular pathways in each pathology may partially temper the natural course of each disorder.
Abstract TP434: Mouse Bilateral Carotid Artery Stenosis Leads to Unexpected Early Changes in Blood-Brain Barrier Integrity
Authors: Roberts Jill , Maniskas Michael , Bix Gregory
Published: June 2021

Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia that is thought to preferentially impact brain white matter. Indeed, it is generally accepted that hippocampal and cortical pathology is not observed prior to 30 days post-injury. Since changes in the blood-brain barrier (BBB) permeability are known to precede more overt brain pathology in a variety of diseases, we hypothesized that BBB changes could occur earlier after BCAS in the hippocampus, striatum and cortex and be a precursor of longer term pathology in these regions. In our study, 3 month old male C57/Bl6 mice underwent BCAS with 0.18 mm coils or sham surgery control and changes in BBB were analyzed by collagen IV (vascular basement membrane component), claudin-5 and occludin (tight junction proteins), Evan’s blue (permeability marker), and Ki-67 (marker of cell proliferation) immunohistochemistry, protein and RNA expression levels after 3, 7, 14, or 21 days. Surprisingly, significant changes in markers of cerebrovascular integrity were detected within 7 days compared to sham animals, not only in the striatum but also in the hippocampus. Increased astrocyte and microglia activation was also observed in these regions and TUNEL staining also indicates cell death in the hippocampus within 7 days. While few changes were observed in the cortex, some of the animals did experience cortical ischemic infarcts within 14 days. In conclusion, this study demonstrates for the first time that changes in the BBB occur shortly after BCAS in multiple regions throughout the brain and suggests that such changes might underlie the gradual development of BCAS non-white matter pathology.
Abstract TP436: Native American Veterans With Vascular Risk Factors Have High Rates of Vascular Cognitive Impairment
Authors: Kirkpatrick Angelia C , Stoner Julie A , Donna-Ferreira Fabiola M , Malatinszky George C , Elias Adreinne M , Guthery Leslie D , Garcia-Martino Daniel A , Makharoblidze Eka , Prodan Calin I
Published: June 2021

Background:
Rates of cardiovascular disease and stroke are elevated in Native Americans, and a greater propensity to develop vascular cognitive impairment (VCI) rather than Alzheimer-type dementia has been inferred, supporting a need for further research in VCI in this population. We determined rates and patterns of memory loss among Native American veterans with multiple vascular risk factors.

Methods:
Native American veterans ≥50 years old with ≥2 vascular risk factors, including smoking history, hyperlipidemia, diabetes, coronary artery disease, or peripheral arterial disease, were recruited between September 2015 and May 2016. The Montreal Cognitive Assessment (MoCA) and the Beck Depression Inventory-II were used to screen for cognitive impairment and depression. Patients with MoCA scores <26 were referred for imaging studies, memory loss serology, neuropsychiatric testing and clinical assessment by a memory loss physician. Final cognitive status was assigned by blinded adjudication.

Results:
We recruited 60 Native Americans aged 50-86 (mean±SD: 64±7.1 years); 90% were male, 95% had at least high-school education, and 69% had some college or advanced degrees. Risk factors included hypertension (92%), hyperlipidemia (88%), diabetes (47%), and prior/current smoking (78%). Eight (13%) with severe depression were excluded, leaving 23/51 with abnormal MoCA scores (44%, 95%CI 30%-59%). All with cognitive impairment were male compared to 83% among non-impaired subjects (p=0.059). Fifteen completed additional evaluation for memory loss, including 4/15 with normal MoCA scores who requested evaluation based on symptoms. Results were adjudicated as normal (4), or as having non-amnestic MCI (4), vascular MCI (5), and vascular dementia (2). MoCA correctly identified cognitive status in 86% (Kappa 0.66, 95%CI 0.23-1.00).

Conclusions:
Native American veterans have high rates of vascular cognitive impairment, which exceed rates of cognitive impairment documented in previously published older non-Native American cohorts. These results highlight the need for improved vascular risk reduction among Native American veterans. Further study is needed to identify ways to improve care in this underserved and understudied population.
Abstract TP437: Asymptomatic Carotid Stenosis is Associated With Cognitive Impairment in a Chinese Community Population
Authors: Jia Jiaokun , Zhao Xingquan
Published: June 2021

Purpose:
This study aimed to investigate the effects of aCAS on cognitive functioning in a Chinese community population who were over 40 year-old and to find the domains of cognitive impairment which were mainly affected.

Methods:
Information was collected on the presence of CAS, which was assessed by Color Doppler Ultrasound, from the Asymptomatic Polyvascular Abnormalities Community study, and cognitive functioning was assessed by the score of the Montreal Cognitive Assessment (MoCA). Multivariate logistic regression was used to assess the relationships between aCAS and cognitive impairment.

Results:
A total of 812 (61.2% men, 55% of 40-60y) patients were included in this study. After adjusting for potential confounding factors, the associations between the aCAS and cognitive impairment remained significant [odds ratio(OR)(95% confidence interval, 95%CI)=1.812(1.049-3.127)]. Also, there were significant relationships between the aCAS and the domains of cognitive function like attention, language, abstraction and recall [OR(95%CI) 2.740(1.494-5.023), 2.005(1.184-3.396), 2.841(1.594-5.065), 4.674(2.478-8.818) respectively, P < 0.05). In addition, there were no interaction effects of age and other possible risk factors on the association.

Conclusion:
In the over 40 year-old Chinese community population, aCAS was an independent indicator of cognitive impairment, especially affecting the function of attention, language, abstraction and recall.

Table 1 Baseline demographic characteristics and cardiovascular risk factors between groups with/without cognitive impairment
Values are median (interquartile range) or number (percent).

Table 2 Unadjusted and Multivariate-adjusted OR (95% CI) for total and subtests of MoCA, according to groups with vs. without CAS.
*P<0.05;**P<0.001

OR: odd ratio; CI: confidence interval

Model 1: adjusted for age and gender.

Model 2: adjusted for age, gender, BMI, education, current smoking and alcohol consumption.

Model 3:adjusted for age, gender, BMI, education, current smoking, alcohol consumption hypertension, diabetes, hyperlipidemia, hs-CRP and Hcy.
Abstract TP439: Occurrence (Incidence and Prevalence) Rate of Delirium and Risk Factors in Acute Stroke - Cross-sectional Study
Authors: Quinn Terence J , Shaw Robert , Taylor-Rowan Martin
Published: June 2021

Introduction:
Guidelines recommend screening all stroke admissions for cognitive impairment. Delirium may be an important contributor to cognitive problems, but available data are limited by potential selection biases and imperfect delirium assessment. We aimed to describe robust estimates of delirium occurrence (incidence and prevalence) and risk factors in an acute stroke unit (ASU).

Methods:
We collected data from sequential admissions to our University Hospital ASU over a 20 week period (Feb-July 2016). The only exclusion was where the clinical team felt that any form of assessment was inappropriate. We aimed to perform cognitive assessments at 48 hours post stroke. Cognitive assessments were based on mini Montreal Cognitive Assessment (m-MoCA) and GP-Cog informant interview to assess for pre-stroke dementia. We assessed for delirium based on DSM-V criteria. We described univariable and multivariable associations with delirium occurrence.

Results:
Across the study period, 184 strokes were admitted; median age 71 years (IQR:61-79). Some form of cognitive assessment was available for 178 (97%). In total. 152 had evidence of cognitive impairment on m-MOCA, 55 (31%) met criteria for delirium and 25 (15%) had pre-stroke dementia. Significant univariable associations with delirium were:age and pre-existing cognitive decline. On logistic regression:age, history of drug or alcohol misuse and pre-stroke mRS were all independently associated with delirium.

Discussion:
In an unselected ASU population a substantial proportion will have cognitive impairment based on screening. Delirium is common and contributes to this cognitive problems seen in acute stroke. Independent associations with delirium occurrence were identified but were non-modifiable. Our results have implications for policy and practice. As post-stroke cognitive impairment is multifactorial, screening delirium and pre-existing cognitive issues should form part of the initial assessment.
Abstract TP440: Elevated Plasma Level of Soluble Form of RAGE in Ischemic Stroke Patients With Vascular Cognitive Impairment
Authors: tang Sung-Chun , Chiou Hung-Yi , Hsu Chung Y. , Wu Chau-Chung , Jeng Jiann-Shing
Published: June 2021

Background / Purpose:
Little is known about the role of receptor for advanced glycation end products (RAGE) -mediated signaling in the development of vascular cognitive impairment (VCI). The study aimed to investigate the associations of various RAGE signaling related plasma biomarkers and the development of VCI in chronic ischemic stroke (IS) patients.

Methods:
This cross-sectional study recruited patients with IS at an university medical center stroke clinic. VCI was defined as the scale of Clinical Dementia Ranking (CDR) ≥1. Standard enzyme-linked immunosorbent assay was used to measure the plasma concentration of soluble form of RAGE (sRAGE), endogenous soluble form of RAGE (esRAGE), high mobility group box 1 (HMGB1) and matrix metallopeptidase 9 (MMP9) in IS patients with and without VCI.

Results:
Between November 2014 to October 2015, a total of 172 IS patients (mean age 72.1±7.5 years, 64.5% male) were recruited, including 73 with CDR=0, 63 with CDR=0.5 and 36 with CDR ≥1. In univariate analysis, IS patients with VCI were older, and had more diabetes mellitus, fewer atrial fibrillation, and higher post-stroke modified Rankin Scales than those without. Plasma levels of sRAGE and esRAGE, but not HMGB1 or MMP9 were significantly higher in IS patients with VCI than those without (1.44±1.29 versus 1.03±0.48 and 0.39±0.40 versus 0.24±0.13 ng/ml, both p<0.01). Importantly, both parameters remained independent after adjustment for clinical variables (OR 2.683, p=0.013 and OR 39.192, p=0.006, respectively).

Conclusion:
Among IS patients, plasma levels of both sRAGE and esRAGE were elevated in those with VCI.
Abstract TP45: Predictors for Good Collaterals in 857 Patients With Acute Ischemic Stroke and Proximal Middle Cerebral Artery Occlusion
Authors: Nannoni Stefania , Cereda Carlo W , Sirimarco Gaia , Lambrou Dimitris , Eskandari Ashraf , Maghraoui Ali , Puccinelli Francesco , Mosimann Pascal , Wintermark Max , Michel Patrik
Published: June 2021

Background:
Good collaterals in acute ischemic stroke (AIS) correlate with smaller infarct size, improved outcome, and better recanalization rates after revascularisation treatments. Given that the variables determining collateral circulation are poorly understood, we aimed to identify predictors of good collaterals in a large series of AIS with middle cerebral artery (MCA) occlusion.

Methods:
In the Acute STroke Registry and Analysis of Lausanne (ASTRAL) from 2003 to 2016, we identified all AIS with MCA occlusion (M1 or proximal M2) on CT angiography (CTA) performed within 24 hours. Collaterals were graded from 0 (absent) to 3 (100% or more) and classified as good (grades 2 and 3) or poor. We correlated collateral status with various clinical, metabolic and radiological variables in a univariate, then multivariate regression analyses (MVA).

Results:
Of the 2’027 patients with AIS involving the MCA and good quality CTA during the study period, 857 met the inclusion criteria. Median age was 72.3±20.5 years, 48.4% were females, and median admission NIHSS was 16±9. Younger age (OR=0.99, confidence interval (CI) 0.98-0.99) and lower NIHSS on admission (OR=0.92, CI=0.90-0.94) were significantly associated with good collaterals. Hyperglycemia (OR=0.94, CI=0.88-0.99) and higher creatininemia (OR=0.99, CI=0.99-1) correlated with poor collaterals. The distribution of vascular risk factors was similar. Radiologically, good collateral status was predicted by higher ASPECTS score (OR=1.31, CI=1.24-1.40), absence of a hyperdense MCA sign (OR=0.60, CI=0.46-0.79), lower clot burden (OR=1.18, CI=1.12-1.24) and absence of proximal intracranial arterial pathology (OR=0.44, CI=0.33-0.58). MVA results will be presented.

Conclusion:
Good collaterals are associated with lower age and lower NIHSS, whereas high blood glucose and creatinine values predicted poor collaterals. On neuroimaging, minor early ischemic changes, lower clot burden and distal site of vascular occlusion correlated with good collaterals. These data may predict stroke outcome in certain patients, explain futile recanalisation, and help select patients for late or aggressive recanalisation treatments independently of time windows.
Abstract TP50: Non-contrast CT Maximum Intensity Projections (MIPs) for the Detection of Large Vessel Occlusion (LVO)
Authors: Ho James P , Nguyen David T , Pirastehfar Mohsen , Narula Rajiv , Hailey Lovella , Mortin Melissa , Rapp Karen , Agrawal Kunal , Huisa-Garate Branko , Modir Royya , Meyer Dawn M , Hemmen Thomas M , Meyer Brett C
Published: June 2021

Background:
Identification of LVO is becoming increasingly important with recent guidelines supporting endovascular therapy in selected patients with acute ischemic stroke (AIS).

Non-contrast CT scans are generally used to assess for stroke or hemorrhage in acute stroke code evaluations. CT angiograms (CTA) can be used to assess for LVO but require additional time and contrast administration. Some hospitals lack the resources to acutely obtain and interpret CTAs. Non-contrast CT MIPs may be an alternate modality to detect LVO.

Methods:
We retrospectively reviewed patients with AIS in our UCSD Stroke Registry, presenting between 6/2014-7/2016 that received a MIPs, generated from non-contrast CT scans, and a CTA. MIPs were evaluated by a group of stroke specialists (3 Faculty, 2 Fellows, 2 Acute Care Practitioners [ACPs]). No clinical information was provided. Gold standard comparison was to CTA. Results were stratified by subgroup based on level of training. Inter-rater agreement was assessed using Fleiss’ Kappa Coefficient.

Results:
24 scans were reviewed (12 with LVO, 12 without LVO).

Using MIPs for the detection of LVO, the Faculty subgroup had a sensitivity and specificity of 81% and 86% for any LVO, 95% and 92% for ICA/M1, 42% and 100% for M2 and 67% and 96% for basilar occlusions. The Fellows and ACPs subgroup had a sensitivity and specificity of 77% and 81% for any LVO, 61% and 94% for ICA/M1, 19% and 83% for M2 and 75% and 95% for basilar occlusions.

Inter-rater agreement among Faculty readers was k=0.58 for the detection of any LVO, k=0.75 for ICA/M1, k=0.79 for M2 and k=0.14 for basilar occlusions. Among Fellows and ACPs, k=0.48 for any LVO, k=0.57 for ICA/M1, k=0.40 for M2, and k=0.27 for basilar occlusions.

Conclusions:
Non-contrast CT MIPs have high sensitivity and specificity for the detection of LVO when compared to CTA. Inter-rater agreement between readers of MIPs is good. Better results in the Faculty subgroup were likely due to more experience reviewing imaging. These results support the use of non-contrast CT MIPs for the detection of LVO to both save time and contrast exposure in patients with AIS. Further studies investigating a larger dataset, optimizing MIP parameters, and examining the utility/cost-effectiveness of this technique are being pursued.
Abstract TP52: Comparison of Two Methods of the Alberta Stroke Program Early CT Score
Authors: Linn Alex J , O’Donnell Steve , de Havenon Adam
Published: June 2021

Introduction:
Alberta Stroke Program Early CT Score (ASPECTS) is a validated clinical tool to predict early ischemic changes in acute ischemic stroke (AIS). In addition to scoring of non-contrast brain CT images (CT), head CT angiogram source images (CTA) have also been demonstrated as useful for scoring. We hypothesized that CTA ASPECTS would show superior inter-rater reliability as compared to CT ASPECTS, and that both would perform better in the setting of the favorable target mismatch (TM) profile on CT perfusion imaging (CTP).

Methods:
We reviewed AIS patients from 2010-2014 with an acute M1 middle cerebral artery occlusion that underwent CT, CTA, and CTP imaging at hospital admission. CT and CTA were independently scored by two experienced physician raters using the standard ASPECTS methodology. Inter-rater agreement was calculated with a weighted kappa. The cohort was then further stratified into either favorable or non-favorable TM profiles using volumetric measurements from the Olea Sphere software and the DEFUSE-3 definition of TM.

Results:
We included 68 patients. The mean±SD age was 62±18 years. 60% were men. The mean NIH stroke scale was 14.5±7.9. The median (IQR) follow-up modified Rankin Scale (mRS) was 3 (1,6). 37 of 68 (54%) patients had the TM profile and were significantly more likely to have lower follow-up mRS scores (z=3.5, p<0.001). Inter-rater agreement of CTA ASPECTS (kappa=0.82) was superior to CT ASPECTS (kappa=0.76). Patients with the TM profile demonstrated more reliable agreement on both CTA and CT ASPECTS scoring systems (kappa=0.79, 0.78), compared to those without the TM profile (kappa=0.71, 0.75).

Discussion:
We found that inter-rater agreement was higher for CTA ASPECTS as compared to CT ASPECTS and that both performed better in patents with the TM profile. Clinically this is important because it reaffirms the utility of CTA ASPECTS in this population of patients in which high reliability is paramount, as ASPECTS is often used in medical decision making when determining eligibility for medical and/or endovascular thrombolytic therapies.
Abstract TP62: To Determine the Evolution of Stroke Volume Overtime Using ANFIS
Authors: Kamran Saadat , Qidwai Uvais , Akhtar Naveed , Bhutta Zain A , Salam Abdul , Shuaib Ashfaq
Published: June 2021

Background:
There is limited information on evolution of temporal lesion volumetric changes in acute ischemia. Though infarct evolves in natural logarithmic or linear pattern in acute phase [24 hrs] both fail to predict the lesion volume in later phase [48,96,200 hours]. Maximum infarct volume [MIV] measured by these methods don’t reach a plateau at the infinite point in time, not true in clinical medicine. Instead of probability based statistical methods we used Adaptive Neuro-Fuzzy Inference System [ANFIS]. ANFIS utilizes features of human brain fundamental to the learning process, pattern modeling and perceptive inference. The purpose is to identify the best method to predict stroke volume at various time intervals.

Methods:
We used pooled hemicraniectomy database to select patients with three CT scans. Measurement of the infarct volume [IV] was done using ABC/2 method. Maximum infarct volume [MIV] was calculated using last CT before DHC. Time was measured from stroke onset to CT. Mean measured MIV was used as standard to compare the outcome by various methods. A Pseudo-Monte-Carlo scheme was utilized in improving the accuracy of the classification.

Results:
There were 66 patients with 3 CT-scans. We used MATLAB-2015 with Fuzzy Logic Toolbox functions to determine the pattern of infarct growth [Linear, Logarithmic, Exponential and ANFIS] and to determine the best predictive method at various time intervals. Of the measured IV on CT 1 and 2, 40 patients [60%] data set was used for training the ANFIS system while remaining 26 [40%] was used for testing. Mean measured MIV was 332±112.21 cm
3
[min 112.86 cm
3
, max 650 cm
3
] at mean time 67.75±67.39 hour [min 21.30 hours, max 350 hours]. Mean MIV measured by ANFIS 319.05±94.58 cm
3
[p=0.32], Linear 251.77±154.46 cm
3
[p=0.01], Logarithmic 259.68±88.76 cm
3
[p=0.00], and Exponential 157.80±84.05 cm
3

Conclusion:
ANFIS predicted the third infarct volume with high degree of accuracy across various time intervals. ANFIS method can provide an excellent model for forecasting infarct volume and growth rate, characterizing the evolution of lesion and pathological stages for mechanistic studies and therapeutic interventions of stroke disease.
Abstract TP65: The Effect of Treatment with Magnesium on the Frequency of Cardiac Comorbidities in Hospitalized Stroke Patients
Authors: Noroozi Jared , Saver Jeffery L , Liebeskind David S , Starkman Sidney , Hamilton Scott , Shkirkova Kristina , Sanossian Nerses ,   FAST-MAG Trial Investigators
Published: June 2021

Background:
Magnesium deficiency is associated with cardiac adverse events such as arrhythmias.

Objective:
We aimed to determine whether early treatment with intravenous magnesium would lower the incidence of major cardiac events among ischemic and hemorrhagic stroke patients.

Methods:
Subjects participated in the NIH Field Administration of Stroke Therapy Magnesium Clinical Trial (FAST-MAG), a phase 3 randomized blinded placebo-controlled study of prehospital initiation of magnesium sulfate (20 grams/24 hours) vs. placebo initiated within 2 hours of symptom onset. Serious cardiac adverse events were recorded and characterized in all participants. We determined the relationship of treatment with magnesium to overall and specific cardiac events.

Results:
There were 1700 cases enrolled in the study with a mean age of 69, 42.7% female, with 1245 cases of cerebral ischemia and 387 cases of intracerebral hemorrhage. Overall there were 255 serious cardiac events recorded in 218 patients (13%), most often cardiac arrhythmia (186 events, 11% of patients) including newly diagnosed atrial fibrillation in 72 (4%), symptomatic bradycardia in 48 (3%) and cardiac arrest in 29 (2%). In subjects with a final diagnosis of cerebral ischemia, treatment with magnesium did not affect the number of overall cardiac adverse events (13.4% with magnesium vs. 14.1% with placebo) or arrhythmia-related events (11.6% magnesium vs 11.7% in placebo). Among cases with intracerebral hemorrhage, treatment with magnesium was associated with a non-significant increased number of serious adverse cardiac events (14% with magnesium vs. 8% with placebo, p = 0.052) and arrhythmia-related events (12.4% vs. 7.3%, p = 0.091). Factors associated with more frequent cardiac events in hospitalized stroke patients were increasing age, history of hypertension, coronary artery disease and atrial fibrillation.

Conclusions:
Prehospital treatment with magnesium did not significantly reduce adverse cardiac events among patients with cerebral ischemia. There were more cardiac events reported in patients with ICH who received magnesium, a finding that may need to be further evaluated.
Abstract TP68: The Characteristics of Acute Ischemic Stroke Treatment Clinical Trials Over the Past Twenty Years: Implications for Future Trial Design
Authors: Dong Yi , Chhatbar Pratik Y , Liu Shimeng , Dong Qiang , Ovbiagele Bruce , Feng Wuwei
Published: June 2021

Introduction:
There was a 20 years span between the landmark NINDS r-tPA trials and the recent spate of positive endovascular trials of acute ischemic stroke. The evolution of clinical trial design, characteristics of subjects, and nature of background standard care have not been properly studied. Such information could have consequences for future clinical trial designs.

Objective:
To systematically search the literature for randomized controlled trials of acute ischemic stroke and identify key patterns.

Methods:
We interrogated Pubmed from 1995 to 2015 with MeSH terms (Fig 1A). Inclusion criteria are: 1) acute intervention delivered within 24 hours of onset; 2) randomized trial with a control (either placebo or standard care) group with ≥20 subjects in each arm; 3) mRS used as an outcome at 3 months; 4) published in the English language. Data were extracted and effect sizes were calculated for both mortality and favorable outcome (mRS: 0-1). We also extracted data for baseline characteristics and analyzed trends over time.

Results:
Forty-six clinical trials were included with 19951 subjects and 38.5% of them were females. There were 8 phase II and 11 phase III trials, nine out of 46 are positive trials
.
Average number of subjects per trial was 443 and number of patient enrollments per year ranged from 23-270. Study-wise odd’s ratio ranged 0.15 - 3.97 for mortality and 0.30- 3.06 for favorable outcomes. Rate of mortality was 13.6% (0-44%) and favorable outcomes ranged 6-37% in control and 7.5-74.8% in intervention arm. Median onset of treatment ranged from 90 - 972 minutes. There are trends of increased NIHSS score at baseline for studies over the years. The type of intervention and baseline NIHSS are major determinants of mortality rate.

Conclusions:
Patterns existed in the acute ischemic stroke treatment trials. Understanding these patterns may inform the stroke community to better design trials in the future.
Abstract TP72: Pilot Trial of Enoxaparin versus Aspirin in Cancer Patients with Stroke: the TEACH Study
Authors: Navi Babak B , Kamel Hooman , Marshall Randolph S , Bobrow Dylan , Singer Samuel , Stone Jacqueline B , DeSancho Maria T , Iadecola Costantino , Elkind Mitchell S , Panageas Katherine S , DeAngelis Lisa M
Published: June 2021

Introduction:
Anticoagulants are often used in cancer patients with acute ischemic stroke (AIS) because of concerns for hypercoagulability. However, cancer patients are also prone to bleeding. No prospective study has compared different antithrombotic strategies in this population. We aimed to perform the first randomized trial comparing anticoagulation to antiplatelet therapy in cancer patients with AIS.

Methods:
We conducted a pilot multicenter randomized trial in adult patients with active systemic cancer and MRI-confirmed AIS. Patients were randomized to subcutaneous enoxaparin (1 mg/kg twice daily) or oral aspirin (81 mg daily) for 6 months. Antithrombotic therapy beyond 6 months was dictated by treating clinicians. Exclusion criteria included clear indications for anticoagulant (e.g., DVT) or antiplatelet (e.g., recent stents) therapy, high-risk conditions for bleeding, symptomatic carotid stenosis, and severe hematologic derangements. Patients were followed at clinical visits at 1, 3, and 6 months and by chart review from 6 months to 1 year. The primary outcome was feasibility, defined as an enrollment rate among eligible patients for which the lower bound of the 95% confidence interval (CI) exceeds 30%. Secondary feasibility outcomes included patient dropout and crossover rates.

Results:
In this interim analysis, 469 patients with cancer and stroke were screened from January 2013 to April 2016 and 49 (10.4%) were eligible. Frequent exclusionary reasons were clear indications for anticoagulation (n=128) and inactive cancer (n=83). We enrolled 20 of the 49 eligible patients, equating to an enrollment rate of 41% (95% CI 27-55%). Enrollment failures primarily occurred because of patient aversion to injections (n=11), patient or physician preference for anticoagulation (n=9), and patient aversion to trial participation (n=7). Thus far, there have been no dropouts but 6 patients crossed over from the enoxaparin arm to the aspirin arm. Major bleeding occurred in 3 patients in the aspirin arm and 1 in the enoxaparin arm; no patients had intracranial hemorrhage.

Conclusion:
A randomized trial comparing anticoagulation to antiplatelet therapy in cancer patients with AIS may be feasible and safe, particularly with an oral anticoagulant.
Abstract TP74: Therapeutic Benefit of Hypothermia After Decompressive Hemicraniectomy in Patients with Ischemic Stroke
Authors: Jeong Won Joo , Yum Kyu Sun , Lee Sangkil , Han Moon-Ku
Published: June 2021

Objective:
Several reports described a beneficial effect of both decompressive hemicraniectomy and therapeutic hypothermia in the management of intractable cerebral edema caused by ischemic stroke. We compared the clinical course and functional outcome in patient with ischemic stroke who were treated with a combination therapy with decompressive hemicraniectomy and therapeutic hypothermia of 33.5°C (DT) or received decompressive hemicraniectomy alone (DA), respectively.

Methods:
We retrospectively reviewed of subjects who were received decompressive hemicraniectomy secondary to ischemic stroke involving the middle cerebral artery, internal carotid artery, or both from 2004 to 2015. 26 patients were treated by DA and 10 patients received a combination of DT. functional outcome was assessed at 30 days and at 90 days.

Results:
Age, initial National institutes of Health Stroke Scale score, volume of cerebral infarction in diffusion weight imaging, risk factors for ischemic stroke were not significantly different between both groups. Median time from symptom onset to decompressive hemicraniectomy were not significantly different. Therapeutic hypothermia was induced after surgery and maintained. (median duration : 159.9 hours). The difference between presurgical and postsurgical midline shift of septum pellucidum and pineal gland in cranial computed tomography scans did not differ significantly between both groups. Duration of need for intensive care or for mechanical ventilation were not significantly different between both groups. There is a difference in mortality rate at 30 days (0% in DT group vs. 26.9% in DA group). The median modified Rankin Scale (mRS) score at 30 and 90 days were 5 and 4, respectively in both groups. Good functional outcome (mRS scores of 0-3) at 90days was observed in 10% of DT group and 5.9% in DA group.

Conclusion:
The present study suggests that a combination therapy of decompressive hemicraniectomy and therapeutic hypothermia improves mortality rate and functional outcome as compared with decompressive hemicraniectomy alone. The main limitation of this study include its retrospective single-center nature, which may limit generalizablility of the study
Abstract TP76: Symptomatic Intracranial Hemorrhage After IV tPA for Acute Ischemic Stroke in Patients with Relative Contraindications
Authors: Smith Kyle C , Alkuwaiti Mohammed , Bell Caitlin , Lindsay Donna , Heyer Angela , Reshi Rwoof , Ezzeddine Mustapha , Streib Christopher
Published: June 2021

Introduction:
Contraindications to IV tPA in acute ischemic stroke (AIS) limits access to a proven medical therapy. A 2015 AHA review assigned Class 3 recommendations (harm) to IV tPA for AIS patients with prior intracranial hemorrhage (pICH), stroke within the last 3 months (SW3), or low platelets (LP) defined as platelets < 100,000. These recommendations, however, were based on sparse literature, notably only 4 AIS patients with pICH and 31 with LP, were reviewed. Our study further investigates the safety of IV tPA in these patient populations.

Methods:
We retrospectively reviewed all AIS cases treated with IV tPA at 2 academic centers from 1998-2015 and 2013-2015. Clinical data, including patient demographics, NIHSS, and relative exclusion criteria, was abstracted from each institution’s prospectively maintained stroke database. Neuroimaging and medical chart review was performed by two stroke neurologists.

Results:
324 consecutive AIS patients treated with IV tPA were reviewed. We identified 12 patients who met current Class 3 exclusion criteria (eight pICH, two SW3, two LP). Two patients developed symptomatic hemorrhagic transformation and both had pICH (Table). For comparison, the symptomatic ICH rate in AIS patients receiving IV tPA without relative exclusion criteria was 2.37%, a statistically significant difference (p<0.02, using Fisher’s exact test).

Conclusions:
12 AIS patients with Class 3 exclusion criteria were treated with IV tPA. Our eight reported cases of IV tPA in pICH patients adds substantially to the existing literature. In this study, 25% of patients with pICH developed symptomatic ICH after IV tPA. Although the low number of eligible patients limits interpretation of our findings, continued caution when considering IV tPA for AIS patients with pICH may be warranted. More data is needed to clarify the impact these relative contraindications have on the treatment of AIS.
Abstract TP79: Inhibition of Toll Like Receptor-4 (tlr4) Improves Neurobehavioral Outcomes After Acute Ischemic Stroke in Diabetic Rats
Authors: Abdul Yasir , Abdelsaid Mohammed , Li Wieguo , Dong Guangkuo , Ergul Adviye
Published: June 2021

Introduction:
Diabetes increases the risk of occurrence and poor recovery of ischemic stroke injury. Activation of adaptive immune system and resulting inflammation contributes to neurovascular injury and deterioration of neurological functions post stroke in diabetes. We have shown that activation of TLR4, a key player in the innate immune system, decreases brain microvascular endothelial cell survival after hypoxic injury in diabetic conditions. Our previous work also demonstrated greater bleeding/edema and poor recovery after stroke in diabetes. Current study tested the hypothesis that activation of TLR4 contributes to worsened stroke injury in diabetes and its inhibition can improve functional outcomes.

Methods:
Low dose of
Streptozotocin (30mg/kg)
and high fat diet were used to induce type 2 diabetes in male Wistar rats. Middle cerebral artery occlusion for 60 mins was performed in 13 weeks old animals. Expression of TLR4 receptor in brain homogenates and cerebral microvasculature were assessed by immunoblotting (relative density). Another set of animals was treated with TLR4 inhibitor TAK242 (3mg/kg; i.p. after reperfusion, 24 and 48 hours). Neurobehavioral deficits were measured by composite score and adhesive removal test at baseline, day 1 and 3 post ischemic stroke.

Results:
Ischemic stroke increased the expression of TLR4 receptor in ischemic hemisphere (0.50±0.06 sham, 0.68±0.02 control and 1.24±2.0* diabetic; *p<0.05 vs sham) as well as in microvasculature (0.55±035 sham, 1.34±0.24 control and 9.49±2.5* diabetic; *p<0.05 vs sham) and this was significantly higher in diabetic animals. Diabetes worsened functional outcomes and inhibition of TLR4 significantly improved the deficits (Table).

Conclusions:
Our findings that TLR4 is highly upregulated in the microvasculature and that beneficial effects of TLR4 inhibition are more profound in diabetes suggest that vascular TLR4 holds a therapeutic potential for stroke recovery in diabetes.
Abstract TP8: A Novel and Thermally Efficient System for Focal Cerebral Hypothermia
Authors: Shoirah Hazem , Nistal Dominic A , Molyneaux Bradley J
Published: June 2021

Background:
Focal cerebral hypothermia via intracarotid cold saline infusion (CSI) is an emerging therapy for acute stroke. Systems of cold saline delivery tested in humans have been thermally inefficient and failed to achieve target cortical temperatures. We applied a set of thermodynamic enhancements to improve thermal efficiency of CSI systems.

Methods:
We replicated the previously described CSI system composed of a cold saline bag (4°C), connected to a 5-Fr diagnostic angiographic catheter immersed in a model of aortic counterflow at 37°C and infusing at a rate of 33 cc/min. Three adjustments were introduced to the system: catheter insulation via a shuttle catheter, higher catheter flow rate (50 cc/min) and external cooling of the system. Those were collectively labeled Cold Preservation via External Cooling, Insulation and Supplemented flow (Cold-PRECISE). We compared the standard system with Cold-PRECISE and with each adjustment separately. Primary outcome was temperatures collected at tubing outlet, catheter tip and the estimated perfusate temperature. We used ANCOVA to compare primary outcomes adjusting for potential confounders.

Results:
Individual system adjustments improved thermal efficiency at all primary endpoints (Table 1).

Compared to standard CSI, insulation and higher flow rate reduced perfusate temperatures by 0.33 and 1.96°C respectively (p <0.001). External cooling reduced tubing outlet by 8.95°C (p 0.03) but had no statistically significant impact on perfusate temperature. The collective implementation of system adjustments had a synergistic effect with catheter tip and perfusate temperatures of 19.57 ± 0.34 and 29.87 ± 0.13 vs 27.13 ± 0.13 and 34.43 ± 0.05 respectively (p <0.001).

Conclusion:
Cold-PRECISE system preserved coldness of locally infused saline, achieving perfusate temperatures that are estimated to meet target cortical temperatures. The clinical efficacy of this system should be evaluated in future clinical trials.
Abstract TP9: ASPECTS Values in Patients With Large Vessel Occlusion and Time of Arrival to Emergency Department: Estimation of Eligibility for Endovascular Stroke Therapy
Authors: Mokin Maxim , Pendurthi Aparna , Primiani Christopher , Burgin William S
Published: June 2021

Background:
Favorable imaging profile according to The Alberta Stroke Program Early CT Score (ASPECTS) is an important selection criterion for endovascular therapy in patients with acute stroke from anterior circulation large vessel occlusion (LVO). The goal of this study was analyze the relationship between ASPECTS values and time of arrival to emergency department (ED) after stroke onset, and its impact on patient’s eligibility for endovascular stroke therapy.

Methods:
analysts of ASPECTS values in consecutive patients with acute stroke from anterior circulation LVO admitted within 24 hours of onset was performed. Criteria from American Heart Association/American Stroke Association (AHA/ASA) guidelines based on the proposed class I-II recommendations, including the ‘favorable’ ASPECTS range of 6-10 were applied to determine frequency of potentially eligible patients for endovascular stroke therapy.

Results:
Of 641 patients with acute ischemic stroke presenting within the first 24 hours of onset, 71 (11%) had anterior circulation LVO. Medium time from arrival to ED to noncontrast head CT was 6 minutes. 72% of patients arrived to ED within the first 6 hours, 18% within 6-12 hours, and 10% within 12-24 hours of symptom onset. Based on ‘favorable’ ASPECTS criterion alone, 80% of patients with anterior circulation LVO who arrive to the ED within the first 6 hours of stroke onset would qualify for endovascular therapy. Of those who arrived to ED within 6-24 hours of stroke onset, 50% had ‘favorable’ ASPECTS.

Conclusions:
50% of patients with stroke from anterior circulation LVO who arrive to ED within 6-24 hours of onset have ‘favorable’ ASPECTS, making them potentially eligible for endovascular stroke therapy.
Abstract TP90: Casein Kinase 2 Inhibition Preserves Axonal Function Against Ischemia
Authors: Brunet Sylvain , Bastian Chinthasagar , Aquila Danielle , Baltan Selva
Published: June 2021

Axonal injury and dysfunction are responsible for much of the disability observed following a stroke. Human brain comprises equal proportions of gray matter and white matter and white matter is injured in most strokes. Casein kinase 2 (CK2) is a protein kinase expressed in brain, including white matter, and is regulated by ischemia. We therefore hypothesized that transient CK2 inhibition would protect white matter from ischemic injury.

To assess the impact of CK2 inhibition on axonal electrical activity following oxygen glucose deprivation (OGD), mouse optic nerves (MONs), a pure white matter track, from C57BL/6J were subjected to OGD (1h) while eliciting compound action potentials (CAPs) and exposed to CX-4945, a selective CK2 inhibitor, or control artificial cerebrospinal fluid (ACSF). We observed that CX-4945 preserved CAPs when applied either before or after OGD. Then to determine the impact of CK2 inhibition on glial cell survival following OGD, MONs exposed to OGD that were treated with either CX-4945 or control ACSF were processed for immunohistochemistry. We observed that CX-4945 treatment protected oligodendrocytes from OGD. And finally, to determine if CK2 inhibition protected mitochondrial from OGD, MONs from Thy-1 mito-CFP mice were similarly subjected to OGD in the presence of either CX-4945 or control ACSF. We observed that CX-4945 maintained Thy-1 mito-CFP fluorescence following OGD.

In conclusion, our results suggest that CK2 inhibition preserves axonal function by preserving oligodendrocytes and mitochondrial function following ischemic injury. We propose that CK2 inhibitors, which are currently in phase II-III clinical trials for cancer therapy could be repurposed and provide a novel therapeutic target to protect white matter against ischemic injury, reducing mortality and morbidity and improving recovery following stroke.
Abstract TP92: Continuous Glyburide Infusion Prevents Hemorrhagic Transformation After Cerebral Infarction in a Rodent Reperfusion Model
Authors: Sastre Cristina , Igarashi Takahiro , Larsen Søren , Wolcott Zoe , Ostwaldt Ann-Christin , Sun Phillip Zhe , Kimberly William Taylor
Published: June 2021

Introduction:
Hemorrhagic transformation (HT) is an uncommon but adverse complication after a stroke that can cause secondary injury. We sought to determine whether glyburide can reduce HT in an ischemia/reperfusion model of stroke.

Materials and Methods:
We used a transient filament occlusion of the middle cerebral artery (tMCAo), with three hours of cerebral ischemia. Glyburide (n=10) was administered as an intravenous bolus followed by a subcutaneous continuous infusion using an osmotic pump to deliver a dose of 39.5 ug/day. Control animals (n=10) were administered dimethyl sulfoxide vehicle. At 48 hours, infarct size, brain edema and HT were analyzed. HT was quantified using three methods, 1) a categorical designation based on European Cooperative Acute Stroke Study (ECASS) criteria, 2) densitometry of color images and 3) direct measurement of the hemoglobin concentration using spectrophotometry.

Results:
Compared to vehicle control, continuous glyburide treatment improved neurological outcome (7.6±1.0 vs. 6.0±0.9, P<0.01), reduced infarct volume (323±42 vs. 484±60mm
3
, P<0.01), swelling volume (10±4 vs. 28±7%, P<0.01) and water content (84±1 vs. 85±1%, P<0.05). Glyburide administration also reduced HT based on ECASS categories, densitometry on color images (0.9±0.1 vs. 1.1±0.1, P<0.01) and quantitative evaluation of hemoglobin (2.7±1.5 vs. 5.1±2.6uL, P<0.05).

Conclusion:
In a prolonged ischemia/reperfusion model, glyburide reduced the amount of hemorrhagic transformation. Clinical evaluation of glyburide in combination with mechanical thrombectomy may be warranted in patients.
Abstract TP99: Inflammatory Changes in Brain and Lymphoid Organs After Ischemic Stroke: PET Imaging for Cell Therapy
Authors: Tan Chengbo , Wang Zifeng , Shichinohe Hideo , Zhao Songji , Kuge Yuji , Kawabori Masahito , Abumiya Takeo , Nakayama Naoki , Kazumata Ken , Houkin Kiyohiro
Published: June 2021

Recently, bone marrow stromal cell (BMSC) therapy for stroke is expected due to the immunomodulation effect. Here, we use PET and other detecting method to investigate the inflammatory changes of brain and lymphoid organs in rat stroke model. In this study, F344 rats were used as transient MCAO models. One part of rats were serially monitored by small-animal PET/CT system with new neuroinflammatory ligand [
18
F]DPA-714. The brains were removed and sliced subsequently for autoradiograph (ARG) and TTC staining. The rest of rats were sacrificed, their brains and lymphoid organs were taken out, weighed, stained, etc. In histology, cytotoxic T cell (CD8α), macrophage (Iba1 and CD68), apoptosis (TUNEL) and proliferation (ki67) antibodies were chosen and analyzed. PET and ARG represented high concentration in the ischemic area which had been confirmed by TTC. In body imaging, no significant change was found. With the increase of ischemic severity, the size of lymphoid organs have a significantly decrease as well as the body weight. Histological assay showed cd8α
+
and ki67
+
cells decreased in the lymphoid organs and increased in brain. Besides macrophages and apoptosis cells increased all the time in liver, in other organs, the rate of cells reached peak and gradually decreased more or less. In summary, [
18
F]DPA-714 PET has a great potential for evaluating brain damage. Inflammatory responses in brain and lymphoid organs are distinct after stroke. Based on these results, we will continue the study for evaluating immunomodulation effect of BMSC transplantation therapy.