bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3874: Galectin-3 Enhances Post Ischemic Angiogenesis Via Modulation Of Integrin And Akt Pathways.
Authors: Wesley Umadevi V , Vemuganti Raghu , Ondoma Solomon , Dempsey Robert J
Published: March 2022

Introduction:
As restoration of blood flow is critical for improved functional recovery following ischemic stroke, enhancing cerebral angiogenesis might be immensely helpful. Galectin-3 (gal-3) is a β-galactoside-binding lectin that plays key roles in inflammation, survival, and angiogenesis.

Methods:
We used transient middle cerebral artery occlusion (MCAO), oxygen-glucose deprivation (OGD) model, western blot analysis, RT-PCR, Immunofluorescence staining.

Results:
We currently report that intra-cerebroventricular infusion of recombinant gal-3 in rats subjected to transient MCAO increases the post-ischemic functional recovery. We further show that gal-3 mRNA and protein expression is up-regulated in vitro when activated microglial BV2 cells were subjected to either oxygen-glucose deprivation (OGD) or LPS (lipo-polysaccharide) stimulation. Immunofluorescence staining showed increased cytoplasmic gal-3 that is known to have pro-survival function. This increase in gal-3 is associated with increased number of pro-angiogenic structures in a 3D human vein umbilical cord endothelial (HUVEC) and microglia co-culture model. The pro-angiogenic effect of gal-3 was suppressed by treatment with gal-3 siRNA indicating the specific role of gal-3 in promoting angiogenesis. Exogenous gal-3 treatment further augmented the angiogenic potential of BV2 microglia cells. In addition, gal-3 increased survival of microglial BV2 cells, HUVEC, and neuro-progenitor cells. Gal-3 levels were also directly correlated with increased levels of Integrin-linked kinase 1(ILK1), pro-survival factor AKT and their down stream effector pro-angiogenic factors bFGF and MMP2.

Conclusion:
Taken together, our studies emphasize the importance of gal-3 in enhancing angiogenesis that is critical for neuron survival and neurogenesis in the post-stroke brain.
Abstract 3917: High-sensitivity C reactive Protein Levels Predict Infarct Growth in Acute Ischemic Stroke
Authors: Lorenzano Svetlana , Li Hua , Rost Natalia , Muzikansky Alona , Caceres J. A , Brouwers H. B , Lima Fabricio , Maas Matthew , Wu Ona , Harris Gordon J , Lo Eng , Feske Steven K , Furie Karen L
Published: March 2022

Objectives:
There is controversy over whether the inflammatory biomarkers detected after focal cerebral ischemia represent a mechanism of tissue injury or simply reflects the extent of ischemic brain injury. In this study we sought to establish whether levels of an inflammatory biomarker (high sensitivity c-reactive protein, hs-CRP) correlate with and predict infarct growth.

Methods:
We prospectively measured hs-CRP in consecutive acute stroke patients (<9 hours from symptom onset) in a multicenter acute ischemic stroke biomarker study. Clinical and demographic data including NIHSS scores at baseline, 48 hours, and discharge, stroke subtype, imaging, and 3 month mRS were collected. Patients with acute infection, active malignancy, or systemic inflammatory disorder were excluded. Infarct growth (IG) was defined as the difference between baseline and t48 hour DWI infarct volume. Multivariate logistic regression model was used to adjust for the effects of potential confounding variables.

Results:
Of 528 subjects enrolled in the biomarker study we included 220 patients with IG, mean age 74 (s.d. 13.8), for whom imaging data were available, in the analysis. The mean IG was 39.9 (s.d.66) cc. We identified cut-off values of IG based on quartiles 50 percentile (15 cc). Subject with IG were more likely to be older, have a higher baseline NIHSS score, a history of carotid stenosis or AF, an anterior circulation stroke, a large vessel occlusion, and larger baseline MTT perfusion deficit. Subjects with IG ≥15cc had a higher mean hs-CRP levels at 48 hours compared to those with an IG <15cc (41.7 mg/L, s.d. 49.6 vs 23 mg/L s.d. 37.7, p=0.011). At multivariate analyses after adjustment for all the confounding variables, 48-hour hsCRP remained independenttly correlated with IG≥15cc.

Conclusions:
High 48 hour levels of hs-CRP were independently associated with larger IG in acute ischemic stroke patients. Hence, if validated, high hs-CRP might be helpful in routine clinical practice to monitor infarct growth and could become a valuable specific surrogate marker of stroke progression.
Abstract 3997: Maintainence of Stroke Certification with Telemedicine
Authors: Miller David A
Published: March 2022

Introduction:
In May of 2010 Mayo Clinic Florida (MCF) partnered with Parrish Medical Center (PMC) in Titusville, Florida to provide remote evaluation and treatment of acute ischemic stroke patients and triage of patients for urgent transfer. PMC was initially accredited as a Joint Commission Primary Stroke Center in 2003. In the 12-month period prior to the telemedicine partnership acute neurology coverage was not continuously available, and the rt-PA utilization rate was 0.8%.

Methods:
Demographic data, baseline stroke severity, time of symptom onset, telemedicine diagnosis, rt-PA utilization, complications, discharge stroke severity and discharge disposition were collected prospectively. Analysis was also performed on the success of the administrative effort, including sharing of patient and statistical information, credentialing, faculty cooperation and patient satisfaction.

Results:
During the first 15 months of the partnership, 193 robotic telemedicine consultations were performed. The mean time from consultation request to telephone response was 3 minutes. 86 patients had a telemedicine diagnosis of stroke and 18 (21%) patients were treated with intravenous rt-PA within 3 hours of stroke onset. Among those treated with iv rt-PA, the mean time from telemedicine evaluation to rt-PA treatment was 54 minutes. The sICH rate was 0%. The median baseline NIHSS was 8.5; the median discharge NIHSS was 2. 18 patients were urgently transferred for consideration of endovascular/surgical stroke therapies. PMC was re-certified as a primary stroke center since by the joint commission in May of 2011 with no deficiencies.

Conclusions:
These data confirm that telemedicine can identify patients eligible for local treatment with intravenous thrombolysis or those who would benefit from urgent transfer to a comprehensive stroke center. Telemedicine can deliver stroke care at the benchmark levels required to maintain primary stroke center certification.
Abstract 45: A Comparison of Outcomes with Early and Delayed Aneurysm Treatment in Subarachnoid Hemorrhage Patients in United States
Authors: Siddiq Farhan , Chaudhry Saqib A , Tummala Ramachandra , Suri M. Fareed K , Qureshi Adnan I
Published: March 2022

Objective:
To identify factors and outcomes associated with timing of ruptured cerebral aneurysm obliteration treatment in patients with subarachnoid hemorrhage (SAH) after hospitalization in United States.

Background:
Recent studies have shown that early surgical treatment of aneurysm in SAH patients can improve outcomes. These results have not been validated in actual clinical practice to date.

Material and Methods:
We analyzed the data from Nationwide Inpatient Sample (NIS 2005-2009) for all patients presenting with primary diagnosis of SAH, receiving aneurysm treatment (endovascular coil embolization or surgical clip placement). Early treatment was defined as aneurysm treatment performed within 48 hours of the hemorrhage and delayed treatment was performed after 48 hours. Clinical outcome was defined as minimal or no disability (self-care), moderate to severe disability (extended care facility) based on discharge disposition; and in-hospital death. Multivariate logistic regression analysis was used to identify the predictors of delayed treatment.

Results:
Out of the 32,048 patients with SAH who underwent aneurysm treatment, 24,085 (75.2%) underwent early treatment and7,963 (24.8%) underwent delayed treatment. Female gender (p=0.0018), teaching hospital status (p=0.103), endovascular embolization (p<0.0001) and weekday admission (p<0.0001) were independent predictors of early treatment. The mean hospital stay was 17.3 days in early treatment group and 19.7 days in late treatment group (p<0.001). In the early treatment group, patients were more likely to discharge with minimal disability (51.1% vs. 47.1% p=0.004, adjusted OR 1.15, 95% CI 1.03-1.29) and less likely to be discharged with moderate to severe disability (34.4% vs. 41.8% p<0.0001, adjusted OR 0.7, 95% CI 0.67-0.86) as compared with those in the delayed treatment group. The in-hospital mortality was higher in the early treatment group compared with delayed treatment (14% vs. 11%, p=0.001, adjusted OR 1.4 95% CI 1.12-1.67).

Conclusion:
Patients with SAH who undergo aneurysm treatment within 48 hours of hospital admission are more likely to be discharged with minimal disability. Early treatment is more likely to occur in teaching hospitals, those undergoing endovascular treatment, and in patients admitted on weekdays.
Abstract 65: Field Neuroprotective Therapy Followed by Intravenous Thrombolysis in a Phase 3 Clinical Trial
Authors: Sanossian Nerses , Kim May A , Starkman Sidney , Liebeskind David S , Hamilton Scott , Eckstein Marc , Pratt Franklin D , Stratton Samuel , Conwit Robin , Saver Jeffrey L ,   FAST-MAG Investigators and Coordinators
Published: March 2022

Background:
A highly promising treatment strategy for acute cerebral ischemia is 1) administration of neuroprotective therapy in the field to stabilize the penumbra, followed by 2) intravenous thrombolytic recanalization therapy to restore blood flow and rescue threatened tissue. The NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study is the first phase 3 RCT testing field initiation of neuroprotective therapy and enrollees are permitted to undergo FDA or national guideline approved recanalization therapies upon hospital arrival when clinically indicated.

Objective:
To characterize rates of utilization of intravenous (IV) thrombolysis with tissue plasminogen activator (TPA) in ischemic stroke patients enrolled in a prehospital study.

Methods:
In FAST-MAG, patients within 2 hours of last known well time transported by 353 ambulances to 59 hospitals are randomized to prehospital-initiated magnesium sulfate vs. placebo.

Results:
Among 1206 consecutive enrolled subjects, final diagnosis of the presenting event was acute cerebral ischemia in 861 (71.4%), intracranial hemorrhage (ICH) in 295 (24.5%), and stroke mimic in 48 (4%). IV TPA was used in 320 patients, 37% of those with a final diagnosis acute cerebral ischemia (ACI, stroke or TIA). Among the ACI patients, none had intracerebral hemorrhage (ICH) on initial imaging study. Among the ACI patients, compared with patients not treated with TPA, TPA-treated patients had worse stroke deficits both in the field (Los Angeles Motor Scale Score 4.2 v 3.35, p<0.0001) and on ED arrival (NIHSS 14 v 7, p<0.0001); and had shorter onset to paramedic evaluation (28 v 43 min, p=0.001) and onset to door (62 v 78 min, p=0.002); and more frequently had a history of HTN (83% v 77%, p = 0.034). TPA treated and non-treated patients were similar in age (71 v 71, p=0.960), sex (female in 47% v 44%, p=0.559), Hispanic ethnicity, race, prehospital and ED systolic and diastolic blood pressures, and other vascular risk factors.

Conclusions:
More than 1 in 3 acute ischemic stroke patients enrolled in the FAST-MAG trial are receiving IV TPA following their field initiation of study agent. When completed, FAST-MAG will have substantial power to evaluate whether there is a synergistic benefit of prehospital neuroprotection and early postarrival thrombolytic reperfusion therapy on clinical outcomes.
Abstract 70: Predicting Recurrent Stroke After TIA And Minor Stroke: Results Of The Prospective CT And MRI In The Triage Of TIA And Minor Cerebrovascular Events To Identify High Risk Patients (CATCH) Study.
Authors: Coutts Shelagh B , Modi Jayesh , Patel Shiel K , Demchuk Andrew M , Goyal Mayank , Hill Michael D
Published: March 2022

Background.
TIA and minor stroke have a substantial risk of recurrent stroke, particularly within the first 48 hours. There is therefore a need to identify the highest risk patients urgently to implement early treatments. Imaging using MRI can identify patients at high risk for a recurrent stroke. However MRI is not available emergently in many institutions. If CT/CTA could identify high-risk patients then this would be more widely applicable.

Methods.
510 consecutive TIA and minor stroke patients who were assessed by a stroke neurologist and had a CT/CTA completed within 24 hours of onset were prospectively enrolled. 420 had baseline brain MRI completed also. We used multiple imputation based on a previous meta-analysis of predictors of DWI positivity (motor or speech symptoms, atrial fibrillation, symptomatic carotid stenosis >=50% and symptom duration greater than 60 minutes) to impute MRI results for patients without baseline MRI. We assessed the risk of recurrent stroke within 90 days using standard clinical variables and predefined abnormalities on the CT/CTA at risk metric (acute ischemia on CT and/or intracranial or extracranial occlusion or stenosis >=50%) and MRI (DWI positivity).

Results.
There were 36 recurrent strokes (7.1% 95%CI: 5.0-9.6). Median time to event was 1 day (IQR 7.5). Median time from symptom onset to CTA was 5.5 hours (IQR: 6.4 hours), median time to MRI was 17.5 hours (IQR: 12 hours). In the univariate analysis; symptoms ongoing at first assessment, HR 2.2 (95%CI: 1.02-4.9), CT/CTA at risk metric, HR 4·0 (95%CI: 2·0-8·5) and DWI positivity 3.2 (1.3-7.6) predicted recurrent stroke. In the multivariable analysis only CT/CTA at risk metric (OR 3.6 (1.7-7.5, p=0.001) and DWI positivity (OR 2.3 (0.9-5.8) predicted recurrent stroke. Diagnostic accuracy of CT/CTA in predicting recurrent stroke was: sensitivity 67%, specificity 68%, PPV 14%, NPV 96%. Diagnostic accuracy of MRI: sensitivity 83%, specificity 40%, PPV 10%, NPV 97%. Using ROC analysis CT/CTA and MRI were not significantly different in their accuracy in prediction of recurrent stroke (0.67 versus 0.61, p=0.18).

Conclusions.
Early assessment of the intracranial and extracranial vasculature using CT/CTA predicts recurrent stroke and clinical outcome in patients with TIA and minor stroke. There is a trade off between sensitivity and specificity when CTA and MRI are compared. In many institutions CTA is more quickly available than MRI and given a median time to event of one day, physicians should access whichever technique is available quicker in their institution to allow implementation of aggressive secondary prevention treatments in appropriate patients.
Abstract 76: Collateral Circulation in Endovascular Therapy for Acute Ischemic Stroke: Smaller Strokes, Improved Reperfusion, Less Hemorrhagic Transformation and Better Outcomes
Authors: Liebeskind David S , Hao Qing , Sanossian Nerses , Choe Jessica S , Fong Albert K , Raychev Radoslav , Ali Latisha K , Kim Doojin , Starkman Sidney , Vespa Paul M , Abcede Hermelinda G , Adamczyk Peter , Gonzalez Nestor R , Tateshima Satoshi , Jahan Reza , Duckwiler Gary R , Vinuela Fernando , Saver Jeffrey L ,   for the UCLA Collateral Investigators
Published: March 2022

Background:
Collateral circulation moderates the impact of acute cerebral occlusion and may influence outcome from recanalization treatment. Noninvasive angiography provides some information on collateral status, but catheter angiography prior to endovascular therapy remains a unique opportunity to verify collateral grade. We conducted a comprehensive study of collaterals in acute anterior circulation occlusion to substantiate previous associations with collaterals and their impact on endovascular stroke therapy.

Methods:
Consecutive patients undergoing endovascular therapy for acute ischemic stroke due to anterior circulation occlusion were analyzed with respect to collaterals. Collateral grade was assessed with the ASITN/SIR scale on baseline angiography. Univariate and multivariate regression analyses detailed the relationship of collateral grade with clinical, laboratory and imaging parameters.

Results:
Among 113 patients, mean age was 66.9±17 years, 61.9% were female, and pretreatment NIHSS was median 17 (range 2-38). The proportion of patients in each collateral grade was: 0 - 3.5% 1 - 13.3 %; 2 - 38.9%; 3 - 31%; 4 - 13.3%. Age and gender were not associated with the degree of collateral circulation. Among medical history and laboratory variables, on multivariate ordinal regression, the sole predictor of more robust collaterals was current statin use (b 1.413, p=0.020) and predictors of worse collaterals were history of hyperlipidemia (b -1.872, p=0.001), White population (b -1.361, p=0.007) and higher WBC (b -0.306, p=0.044). More extensive collaterals correlated with smaller baseline DWI lesion volume (b 0.025, p=0.001). Interestingly, angiographic collateral grade did not correlate with PWI lesion volumes for Tmax thresholds at 2, 4, 6, or 8 seconds. More robust collaterals were associated with higher TICI reperfusion rates (ρ 0.191, p=0.043), and lower hemorrhagic transformation rates (ρ -0.229, p=0.015). mRS at discharge inversely correlated with collateral grade (ρ -0.317, p=0.001).

Conclusions:
The extent of collateral circulation prior to endovascular therapy exhibits a striking impact on achievement of reperfusion, tissue fate and functional outcome. Further research is needed to delineate mechanisms linking statins with better collaterals and biomarkers, such as elevated WBC, for arteriogenesis when collaterals are insufficient.
Abstract 92: MRI Patient Selection In Acute Stroke Trials: Implications For Sample Size
Authors: Lansberg Maarten G , Lee Jun , Christensen Soren , Straka Matus , De Silva Deidre A , Mlynash Michael , Campbell Bruce C , Bammer Roland , Olivot Jean-Marc , Desmond Patricia , Davis Stephen M , Donnan Geoffrey A , Albers Gregory W ,   The DEFUSE-EPITHET Investigators
Published: March 2022

Background:
MRI selection of patients with acute stroke may reduce the required sample size for randomized controlled trials of interventions aimed at restoring blood flow. The Target Mismatch pattern has been proposed as a MRI-marker that can differentiate patients who are likely to benefit from reperfusion from those who will have no effect from or may be harmed by reperfusion. The Target Mismatch pattern is present in approximately 50% of stroke patients with a middle cerebral artery occlusion who present in the 3-6 hour time-window. The pattern is based on the following PWI and DWI criteria: ratio of Tmax>6s over DWI volume >1.2, difference between Tmax>6s and DWI volume >10ml, and DWI volume <100ml. The aim of this study was to compare the required sample size of acute stroke studies that use MRI selection to that of studies which do not use MRI selection.

Methods:
All sample size calculations were based on an alpha of 0.05 in a two-sided test and a desired power of 0.8. MRI patient selection was assumed to be according to Target Mismatch criteria. The primary study outcome was assumed to be good functional outcome, defined as a modified Rankin Scale of 0-2 at 90 days. Other assumptions for the sample size calculations were based on data from the literature and data from the pooled EPITHET-DEFUSE database regarding patients with middle cerebral artery (MCA) occlusions treated up to six hours after symptom onset. The spontaneous reperfusion rate in this population was assumed to be 0.22. For MRI-selected mismatch patients the rate of good functional outcome was assumed to be 0.73 with reperfusion and 0.30 without reperfusion. For unselected patients, the rate of favorable clinical outcome was assumed to be 0.67 with reperfusion and 0.41 without reperfusion.

Results:
A trial of an intervention that leads to reperfusion of the MCA in 45% of patients would require 396 patients per group if MRI selection criteria were applied and 1096 patients per group without MRI selection criteria. A trial of an intervention that has a 70% reperfusion rate would require 92 patients in each arm if MRI selection criteria were applied versus 251 patients per arm if patients were enrolled without MRI selection. (see
figure
)

Conclusion:
MRI selection can markedly reduce the required sample size of randomized controlled stroke trials in the delayed time-window. This advantage needs to be balanced against the potential drawbacks of using a MRI-marker as an inclusion criterion for a randomized controlled trial.
Abstract 93: Relation Between Outcome and Infarct Size and Location in Brainstem Stroke
Authors: Quigley Matthew R , Chew Brandon , Tayal Ashis , Wright David , Tian Melissa
Published: March 2022

Introduction:
Although MR is frequently used for the diagnosis of brainstem stroke, there is little consensus regarding the ultimate prognostic implications of the findings.

Hypothesis:
MR imaging characteristics will be useful in the determination of outcome following brainstem infarction.

Methods:
We performed a retrospective review of patients treated for basilar distribution infarction at a Joint Commission Certified Primary Stroke Center and identified through a prospective registry begun in 8/06. Standard demographic and clinical data were recorded on admission and MR scans analyzed. Routine 5mm T2 and DWI sequences were utilized starting at the level of the P2 vessel, comprising 2 midbrain, 3 pontine and 3 medullary slices. Volumes were computed by manually tracing the signal abnormality and employing the supplied software package (Carestream PACS, Rochester NY). Outcomes were dichotomized as non-functional (dead, comatose, locked-in) and functional (all others) at 6 months.

Results:
There were 38 patients in the registry, of whom 25 had MR documented brainstem infarctions. There were 11/14 M/F, average age 64.7 years. Average admit NIHSS was 17.4 and the LOS was 21.5 days. MR was performed at a median of 1 day post admission. Mid-pontine was the most common stroke location (19/25) and about half of the DWI lesions (12/25) crossed midline. Outcome was deceased in 8 (5 in-hospital, 3 hospice), 4 locked-in and 13 functional survivors. Both T2 and DWI volumes correlated with outcome (p<.0001), but DWI was slightly superior (AUC/ROC .865/.862). DWI volume, not T2, correlated with initial NIHSS (p=.05, linear regression). In the stepwise logistic regression, DWI volume alone correlated with functional survival (p=.0003), not age, admission NIHSS, midline-crossing lesions nor anatomic location. DWI volume predicted 86% of the variation in outcome (c-statistic) and no patient with a DWI volume >3cm3 had a functional outcome.

Conclusion:
In this population of patients with brainstem stroke, MR appears to be a potent tool for predicting outcome with DWI volume being the most useful indicator.
Abstract 102: Adherence to ECASS III 3-4.5 Hour Exclusion Criteria and Association with Outcome in Clinical Practice: Data from Get With The Guidelines (GWTG)-Stroke
Authors: Cronin Carolyn A , Sheth Kevin N , Zhao Xin , Messe Steven R , Olson DaiWai M , Hernandez Adrian F , Bhatt Deepak L , Schwamm Lee H , Smith Eric E
Published: March 2022

Introduction:
AHA/ASA guidelines recommend IV tPA treatment 3-4.5 hours from symptom onset according to criteria used in the ECASS III study. However, ECASS III excluded certain patient groups in addition to the standard exclusions for <3 hours in the USA: age >80, history of stroke and diabetes, oral anticoagulant treatment, and NIHSS>25. We investigated adherence to these additional exclusion criteria for patients treated 3-4.5 hours from symptom onset, and their association with outcome.

Methods:
We analyzed data from GWTG-Stroke on 32,019 ischemic stroke patients from 1464 hospitals who were treated with IV tPA within 4.5 hr of symptom onset from January 2009 to January 2012, excluding patients transferred from an outside hospital. The percent of patients meeting vs not-meeting each exclusion criterion were compared between treatment time windows. For each criterion, outcomes were compared for patients treated <3 vs. 3-4.5 hr. P-values were based on Pearson Chi-square test.

Results:
Overall, 1544/4910 (31.5%) of patients treated with IV tPA in the 3-4.5 hour window had at least one of the additional exclusions. The most common additional exclusion among treated patients was age > 80. With the exception of prior stroke and diabetes, the percent of tPA treated patients with each exclusion criterion was lower at 3-4.5 hr compared with <3 hr (Table 1A). For each of the additional exclusion criteria, there was no difference in sICH or hospital outcome for patients treated <3 vs. 3-4.5 hr (Table 1B).

Conclusions:
Patients with ECASS III-specific exclusion criteria for the 3-4.5 hr window are frequently treated with IV tPA in the U.S. The exclusion criteria were not associated with worse outcomes in the 3-4.5 hr window compared to the <3 hr window.
Abstract 108: Transcriptional and Epigenetic Regulation of MCP1 by Tumor Necrosis Factor-a and Cigarette Smoke: Key Mediators in Aneurysm Formation
Authors: Ali Muhammad S , Starke Robert M , Jabbour Pascal M , Tjoumakaris Stavropoula I , Gonzalez L. Fernando , Rosenwasser Robert H , Koch Walter J , Dumont Aaron S
Published: March 2022

Background:
Although the underlying pathophysiology involved in aneurysm formation and progression is unknown, both cigarette smoke and alterations in the inflammatory cascade play a key role. We investigated the role of TNF-α and cigarette smoke extract (CSE) induction of an inflammatory phenotype in cerebral vascular smooth muscle cells (VSMC) through regulation of Monocyte Chemoattrant Protein-1 (MCP-1) and Kruppel Like Factor-4 (KLF4).

Methods:
Cultured cerebral VSMC from rat Circle of Willis were treated with increasing doses of TNF-α and CSE. siRNA specific to KLF4 was transfected into cells, followed by TNF-α and CSE treatment. In vivo, experiments were performed by applying TNF-α and CSE infused pluronic gel to rat carotid artery adventitial surface. MCP1 activity was measured with qPCR. Aneurysm induction surgery was performed in rats, and mRNA from the Circle of Willis was measured with qPCR. Chromatin Immunoprecipitation (ChIP) was performed both in vitro and in vivo using anti-KLF4, anti-histone deacetylase 2 (HDAC2), and anti-histone 4 acetylation (H4Ac) antibodies.

Results:
TNF-α and CSE treatment for 24-hours increases the expression of MCP-1 both in vitro and in vivo. Treatment with siKLF4 abrogates this inflammatory phenotype. Similarly, increased expression of TNF-α, KLF4, and MCP-1 was found after aneurysm induction in vivo. TNF-α and CSE initiated KLF4 binding to the MCP-1 promoter region in ChIP assays. This increases H4 acetylation and decreases HDAC2 binding to the promoter region resulting in MCP-1 stimulation.

Conclusion:
TNF-αand CSE induce an inflammatory phenotype in cerebral VSMC by regulating the expression of MCP-1. KLF4 plays a critical role in this process through binding to the promoter region and induction of epigenetic changes favoring MCP-1 expression. MCP-1 upregulation and subsequent inflammatory cell recruitment is likely a key mechanism in cerebral aneurysm formation and may be an important target for future therapy.
Abstract 113: The Intracerebral Haemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT): Final Results.
Authors: Butcher Ken S , Jeerakathil Thomas , Hill Michael , Demchuk Andrew M , Dowlatshahi Dariush , Coutts Shelagh B , Gould Bronwen , McCourt Rebecca , Asdaghi Negar , Findlay Max , Emery Derek , Shuaib Ashfaq ,   for the ICH ADAPT Investigators
Published: March 2022

Background:
Acute blood pressure (BP) reduction aimed at attenuation of intracerebral hemorrhage (ICH) expansion might also result in a harmful compromise of cerebral blood flow (CBF) in the region surrounding the hematoma. We tested the hypothesis that CBF in acute ICH patients is affected by BP reduction.

Methods:
Seventy-five patients with spontaneous ICH with baseline systolic BP>150 mmHg were randomly assigned to an intravenous antihypertensive treatment protocol (labetalol, hydralazine and enalapril) targeting a systolic BP of either <150 mmHg or <180 mmHg within 24 hours of symptom onset. Patients underwent CT perfusion (CTP) imaging 2 hours post-randomization. The primary endpoint was relative CBF (rCBF) within the 1 cm perihematoma region.

Results:
Treatment groups were balanced with respect to baseline systolic BP: 182±20 mmHg (<150 mmHg target group, n=39) vs. 184±25 mmHg (<180 mmHg target group, n=36, p=0.60), hematoma volume: 25.6±30.8 vs. 26.9±25.2 ml (p=0.66) and median (IQR) time to randomization: 7.8 (13.5) and 8.5 (11.9) h (p=0.94). Mean systolic BP two hours after randomization was significantly lower in the <150 mmHg target group (140±19 vs 162±12 mmHg in the <180 target group, p<0.001). Perihematoma CBF (38.7±11.9 ml/100g/min) was lower than in contralateral homologous regions (44.1±11.1 ml/100g/min, p<0.001) in all patients. The primary endpoint of perihematoma rCBF in the <150 mmHg target group (0.86±0.12) was not significantly lower than that in the <180 mmHg group (0.89±0.09, p=0.19; absolute difference 0.03 95% CI -0.018, 0.078). There was no relationship between the magnitude of the BP change and perihematoma rCBF in the <150 mmHg (R=0.00005, 95% CI -0.001, 0.001) or <180 mmHg target groups (R=0.000, 95% CI -0.001, 0.001). There were no effects on rCBF in patients treated within 6 hours (0.78±0.22 in the <150 mmHg group and 0.88±0.10 in the <180 mmHg group, p=0.08) or in those treated 6-24 hours after onset (0.85±0.21 in the <150 mmHg group and 0.89±0.10 in the <180 mmHg group, p=0.46).

Conclusions:
Rapid BP lowering following ICH does not reduce perihematoma CBF. These physiological data support the safety of acute and aggressive BP reduction following ICH.
Abstract 134: Agonaute 2 Regulates Neurogenesis In Ischemic Neural Progenitor Cells
Authors: Liu Xianshuang , Michael Chopp , Wang Xinli , Kassis Haifa , Zhang Ruilan , Cui Yisheng , Zervos Thomas , Zhang Zhenggang
Published: March 2022

Background:
Molecular mechanisms underlying stroke-induced neurogenesis have not been fully investigated. Argonaute 2 (Ago2) is the central component of RNA-induced silencing complex (RISC) that regulates miRNA activities. We investigated the biological functions of Ago2 in neural progenitor cells (NPCs) under normal and ischemic conditions.

Methods and Results:
Adult rats were subjected to permanent right middle cerebral artery occlusion (MCAo). Double immunofluorescent data revealed that stroke significantly (p<0.05) increased the number of Ago2
+
neuroblasts (doublecortin, DCX
+
, 31±4 vs 13±4 in non-MCAo control, n=6/group) in the subventricular zone (SVZ). To examine the role of stroke-upregulated Ago2, we selectively attenuated endogenous Ago2 in NPCs isolated from the ischemic SVZ with siRNA. Attenuation of endogenous Ago2 suppressed stroke-induced NPC proliferation (bromodeoxyuridine
+
, BrdU
+
cells, 45±3 vs 61±5% in scrambled siRNA group, n=6/group, p<0.05), reduced the size of neurospheres (169±44 vs 224±40 μm, n=7/group, p<0.05), and increased the percentage of TUNEL
+
cells (37±5 vs 15±5%, n=6/group, p<0.05). Ablation of Ago2 also significantly reduced the percentage of stroke-increased neuroblasts (Tuj1
+
cells, 4±1 vs 9±1%, n=6/group, p<0.05). Using high-throughput deep-sequencing of RNAs isolated by Ago2 crosslinking immunoprecipitation (Ago2 HITS-CLIP) analysis, we found that stroke substantially increased the copy numbers of miRNAs including miR-21 and miR-214, which were expressed at relatively low levels in non-ischemic NPCs. Attenuation of endogenous Ago2 by siRNA reduced Ago2-enriched miRNAs induced by stroke, whereas overexpression of Ago2 increased these miRNA expression.

Conclusion:
Our data suggest that Ago2 regulates miRNA biogenesis in NPCs after stroke, which provides new insight into molecular mechanisms of stroke-induced neurogenesis.
Abstract 168: Prospective Nationwide Registry of Acute Stroke due to Large Vessel Occlusion in Japan
Authors: Yoshimura Shinichi , Sakai Nobuyuki , Okada Yasushi , Kitagawa Kazuo , Kimura Kazumi , Tanahashi Norio , Hyogo Toshio , Yamagami Hiroshi , Egashira Yusuke ,   RESCUE-Japan Prospective Registry Group
Published: March 2022

Background:
The multicenter prospective registry of Japan (RESCUE-Japan Registry) was performed to clarify the clinical impact of endovascular treatment (EVT) on acute stroke due to large vessel occlusion.

Methods:
Patients admitted within 24 h after onset were prospectively registered from July, 2010 to June, 2011. The efficacy of rescue EVT for intravenous intravenous tissue plasminogen activator (IV-tPA)-failed patients was analyzed.

Results:
Among a total of 1,454 patients registered from 84 medical centers, 1,442 patients (633 women, 899 men) with 3 months outcome were analyzed. Mean age was 74.0 years, and mean arrival time was 233.4 min after onset, and mean NIHSS was 15.5 points. As the revascularization treatment within 3 h, IV-tPA was performed in 51%, EVT in 16% and their combination in 17%. In the patients treated with IV-tPA (n=194), significant recanalization (TICI 2B and 3) was obtained in 29-39% in MCA, but less than 15% in ICA on cerebral angiogram performed 1 to 3 h after IV-tPA (Fig1). Rescue EVT after IV-tPA was performed in 129 patients (17%), and increased significant recanalization (17% to 68%) (Fig.2) and favorable outcome (mRS:0-2) in the ICA (22% vs 48%, p=0.007) (Fig. 3), but not symptomatic intracranial hemorrhage (6.1% vs 4.1%) (p=0.35).

Conclusions:
This registry suggested the efficacy of rescue EVT in IV-tPA failed patients, especially with ICA occlusion.
Abstract 174: MRI Findings Associated with Neurocognitive Impairment One Year after Primary Intracerebral Hemorrhage in a Predominantly Black Cohort
Authors: Edwards Dorothy F , German Laura , Memon Ravi S , Wing Jeffrey J , Tiffany Deirdra , Fernadez Stephen , Smith Keisha , Jayram-Trouth Anapurni , Gibbons M. C , Kidwell Chelsea S
Published: March 2022

Background:
We previously reported racial differences in neurocognitive outcomes assessed 1 year after primary ICH in the DiffErenCes in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) study.. We now analyze MR imaging findings associated with cognitive impairment in this cohort.

Methods:
Inclusion criteria were primary ICH, age >18, MRI at baseline, neurocognitive outcomes measured at 30 days and 1 year. Domains assessed included memory, executive function, attention, verbal fluency, depression and functional outcome. African American normative data were used to establish cut-points. The following variables were evaluated on MRI: evidence of prior stroke, hemorrhage volume and location, presence of microbleeds, and severity of white matter disease (WMD). Independent t- tests, chi-square, or Fisher’s exact tests were used as appropriate to compare differences between groups at 30 days and 1 year.

Results:
Of 192 subjects enrolled, mean age was 59 ± 13 years, 47% were female, and 76 % were black. Mean NIHSS was 10 (median 7). Neurocognitive outcomes were available for 144 subjects at 30 days and 126 at 1 year. Significant impairment was observed for all domains at each interval: memory (30 days 90%, 1 year 86%), verbal fluency (30 days 83%, 1 year 74%), attention (30 days 50%, 1 year 52%), and executive function (30 days 51%, 1 year 54%). Dementia was present in 22% at 30 days and 13% at 1 year. At 1 Year, hemorrhage location was not significantly associated with cognitive impairment, however, evidence of prior stroke was associated with impaired executive function (p<0.02). The presence of microbleeds was associated with impaired verbal fluency (p<.03) and executive function (p<.04).White matter disease had the greatest impact on neurocognitive and functional outcomes, with WMD scores >6 associated with impaired memory (p<0.004), executive function (p=0.01) ,verbal fluency (p=0.03), attention (p=0.03) and mRS scores > 2 (p<.005).

Conclusion:
While the overall rates of neurocognitive and functional impairment decreased over time significant effects of primary ICH persist at 1 year and are associated with MR imaging findings of underlying vascular small vessel injury, including the presence of microbleeds and white matter disease.
Abstract 67: Importance Of Previous Brain Infarcts In Patients With Asymptomatic Carotid Stenosis And The Impact Of Surgery From The Asymptomatic Carotid Surgery Trial-1
Authors: Streifler Jonathan Y , denHartog Anne G , Pan Samuel , Thomas Dafydd , Halliday Alison ,   ACST-1 trial collaborators
Published: March 2022

Background and aims:
Silent brain infarcts are common in patients at increased risk of stroke and are associated with a poor prognosis. Similar adverse associations were claimed in asymptomatic carotid stenosis (ASCS) patients but the impact of previous infarction or symptoms on the beneficial effects of carotid endarterectomy (CEA) is not clear. Our aim was to evaluate the importance of prior brain infarcts (PBI) in ASCS patients enrolled in ACST-1 - a large trial with 10-year follow-up.

Methods:
Of 3120 patients included in ACST-1, 787 patients without baseline imaging were excluded. Trial patients (2333) with brain imaging at trial entry were identified & divided into those with PBI (i.e. radiological evidence of an asymptomatic infarct or prior ischaemic symptoms [PIS] >6 months prior to randomization) (group 1, 1331 patients) & those with normal imaging and no PIS (group 2, 1002 patients). The trial allocated immediate CEA treatment to about half of the patients in both groups. First stroke and vascular death in these groups were compared during follow-up irrespective of treatment assignment and, for both groups, the impact of CEA was analyzed.

Results:
Baseline characteristics of excluded & analyzed patients were similar, male gender and hypertension being commoner in group 1 with slightly tighter ipsilateral stenosis in group 2. After 10 years stroke was significantly commoner in group 1 (absolute risk increase [ARI] 5.8% [1.8-9.8], p=0.004) as was risk of stroke and vascular death (6.9% [1.9-12.0] ARI, p=0.007). Multivariate analysis confirmed that PBI was associated with greater risk of stroke (HR=1.51 95%CI:1.17-1.95) and of any stroke or other vascular death (HR=1.30 95%CI:1.11-1.52). Benefits of CEA at 5 years appeared greater for group 1 patients (gain 4.9% p=0.005%) than for group 2 (gain at 5 years, 3.9% p=0.02%) though it must be emphasized that the trial was not designed to test this comparison.

Conclusions:
ASCS patients with prior brain infarcts have higher stroke risk during long-term follow-up than those without PBI and may benefit more from CEA.
Abstract 88: Primed Therapy Accelerates Recovery of Upper Limb Function after Stroke
Authors: Stinear Cathy M , Petoe Matthew , Anwar Samir , Barber Peter A , Byblow Winston D
Published: March 2022

Background:
Upper limb impairment is common after stroke and recovery of upper limb function reaches a plateau within 6 months for most patients. We hypothesised that recovery can be accelerated by increasing the excitability and plasticity of the ipsilesional motor cortex, so that it is primed for upper limb therapy. This study tested the effects of priming upper limb therapy with Active Passive Bilateral Training (APBT).

Methods:
We enrolled 57 patients with first-ever monohemispheric ischaemic stroke in this randomised, controlled, single-centre, double-blinded trial. Priming consisted of 15 minutes of APBT, where patients actively flexed and extended their non-paretic wrist in a mechanical device, which moved their passive paretic wrist in mirror-symmetric flexion and extension. The control intervention consisted of 15 minutes of weak cutaneous electrical stimulation. Both groups completed the intervention prior to 20 minutes of upper limb therapy, 5 d/w for 4 w, starting 2 w after stroke. Upper limb function was assessed with the Action Research Arm Test at 2, 6, 12 and 26 w. Corticomotor excitability was assessed with transcranial magnetic stimulation. Corticospinal tract integrity and cortical activity during isometric grip with the paretic hand were assessed with MRI. The primary endpoint was recovery of upper limb function at 12 w, using Intention to treat (ITT) and per protocol (PP) analyses.

Results:
Primed patients were 3 times more likely than control patients to reach at least 75% of their maximum recovery within 12 w (ITT OR 2.7, 90% CI 1.1 - 7.0; PP OR 3.4, 90% CI 1.2 - 9.9). Corticomotor excitability was normalised to a greater extent following primed therapy than control (F3,129 = 2.91, p = 0.037).

Conclusion:
Priming upper limb therapy with APBT accelerated recovery of upper limb function and normalised motor cortex excitability. APBT is a simple, inexpensive way of enhancing the neural response to therapy and may increase the efficiency of upper limb rehabilitation after stroke.
Abstract 93: Androgen Regulation of Protection Provided by Inhibition of TRPM2 Channels against Experimental Stroke in Mice
Authors: Shimizu Takeru , Coleman Jake , Herson Paco S
Published: March 2022

Introduction:
Stroke is a sexually dimorphic disease that affects men more severely than women. Transient receptor potential (TRP) channels have been implicated in ischemia-induced neuronal damage. We recently demonstrated that pharmacological and genetic inhibition of TRPM2, a member of the TRP channel superfamily, protects against cerebral ischemia in male mice, while having no effect in females. In addition, TRPM2 channels are activated by adenine dinucleotide phosphate ribose (ADPr) generated by poly(ADPr) polymerase (PARP). In this study, we examined the role of male sex steroids in TRPM2 engagement following experimental stroke.

Methods:
Focal ischemia was induced by 60 min of middle cerebral artery occlusion in male C57Bl/6 mice. To assess the efficacy of post-insult administration of TRPM2 inhibitor clotrimazole (CTZ), intact mice were treated with either CTZ (30 mg/kg) or vehicle 1 h after reperfusion. Mice were castrated (CAST) in order to remove sex steroids and either dihydrotestosterone (DHT) or vehicle was implanted. Then, animals were treated with either CTZ or vehicle 1 hr after reperfusion. The infarct sizes were evaluated in TRPM2
-/-
mice to confirm TRPM2 engagement. We further compared the PARP activity in intact male and female brain to that in ischemic brain.

Results:
Animals treated with CTZ had significantly smaller infarcts compared to vehicle treated animals (46.2±3.1% (n=8) in vehicle vs. 32.5±3.6% (n=8; P<0.05) in CTZ). Removal of sex steroids resulted in loss of protection by CTZ (44.6±3.1% (n=9) in vehicle treated CAST vs. 35.8±3.6% (n=11) in CTZ treated CAST). Androgen replacement with DHT (CAST+DHT) resulted in recovery of CTZ protection (40.4±2.3% (n=12) in vehicle vs. 31.5±2.8% (n=11; P<0.05) in CTZ). TRPM2
-/-
mice had smaller infarcts compared to wild type (28.4±7.0 (n=5) vs. 49.0±1.2 (n=5); P<0.05). We found higher PARP activity in male penumbral tissues compared to male normal tissues (P<0.05), while having no difference in females.

Conclusions:
These data indicate that TRPM2 inhibition provides protection from ischemic stroke in male animals in an androgen-dependent manner. Therefore, androgen status must be considered when considering inhibition of TRPM2 channels as a potential therapeutic strategy in men.
Abstract NS8: Colorado’s First Nurse Facilitated Transient Ischemic Attack Clinic: The New Paradigm for Transient Ischemic Attack Treatment
Authors: Kimminau Kryssy , Woodard Jim
Published: March 2022

The risk of a disabling stroke after a Transient Ischemic Attack (TIA) is suggested to be highest within the first 48 hours after the TIA event and nearly half of recurrent stroke events ensue within the first 7 days. The TIA Clinic at Porter Adventist Hospital was developed to promote timely, efficient, and comprehensive treatment services for patients, allowing for targeted long term follow-up. Patients presenting with a TIA have limited options for receiving efficient evaluation and follow-up care. They can be admitted to hospitals for further diagnostic testing, seek care at their PCP or attempt to find a neurologist. Unfortunately these options are often expensive and can be the cause of treatment delays. Patients admitted to the hospital often incur higher out of pocket expenses, lost work time and exposure to hospital acquired conditions.

The interdisciplinary service provides evaluation of TIA etiology and enables secondary stroke-prevention interventions to be initiated the day of patient’s evaluation. Once diagnostic procedures are completed, the neurologist finalizes the TIA etiology, risk-factor profile, and recommended secondary prevention strategies.

Measurement strategies are obtained through patient satisfaction survey at the end of clinic, ninety day phone call follow-up and physician e-mail follow-up. The clinical nurse coordinator collects post-clinic data on this group of patients. After evaluation of 54 patients since the clinics inception there was no recurrence of TIA or stroke symptoms with 90 day follow-up in any patient. In addition, the clinic has proven to provide (1) expedited consultations and diagnosis as available to hospitalized patients; (2) identification and treatment of patients who have actually had a stroke rather than TIA; (3) identification and treatment of “stroke-mimicking” diagnoses such as migraine with aura, seizure, hypoglycemia, arrhythmias, intracerebral hemorrhage and intracranial tumor; and (4) identification of stroke risk factors and rapid implementation of specific interventions in the most vulnerable period for disabling stroke (i.e., the first 2-7 days).
Abstract TMP106: Validation Of The Factors Affecting Basal And Fluctuating Warfarin Doses In The Same Individual Throughout The Year In Japanese Patients
Authors: Tanaka Tomotaka , Yamamoto Haruko , Kada Akiko , Yasaka Masahiro , Hasegawa Yasuhiro , Koretsune Yukihiro , Miyata Shigeki , Miyata Toshiyuki , Nagatsuka Kazuyuki
Published: March 2022

Background:
Vitamin K epoxide reductase (VKORC1) and cytochrome p450 isoform (CYP2C9) genotypes contribute to basal therapeutic warfarin doses. Although safe introduction of warfarin is possible, prothrombin time-international normalized ratio (PT-INR) fluctuations requiring continuous adjustment of warfarin doses have been observed in the same patient. Of late, nongenetic factors, in particular renal function, have been associated with warfarin maintenance dose and decreased anticoagulation stability; however, the mechanism of decreased anticoagulation stability has not been identified. This study aimed to elucidate the factors that affect basal and fluctuating warfarin maintenance doses.

Methods:
This study was a prospective, multicenter, observational study. Patients who were prescribed warfarin for thromboembolism were enrolled. Patient characteristics and
CYP2C9
and
VKORC1
genotypes were recorded. To evaluate anticoagulation stability and patient management, we measured PT-INR, estimated creatinine-based GFR (eGFR), and vitamin K intake and examined the warfarin maintenance doses and requirement of warfarin dose change four times a year (seasonally). Vitamin K intake was assessed by a semi-quantitative food frequency questionnaire. Multivariate logistic regression analysis was used to determine the factors affecting basal warfarin doses and PT-INR fluctuations or the necessity of adjustment of warfarin dose.

Results:
We analyzed the data of 327 patients. Genotyping results of
CYP2C9
and
VKORC1
showed that 80% patients had wild type
CYP2C9
and the AA genotype of
VKORC1
. eGFR was 63.2 ± 18.0 ml/min/1.73 m
2
. Vitamin K intake was 100.0 ± 60.9 μg/day in spring, 91.5 ± 53.8 μg/day in summer, 98.5 ± 69.1 μg/day in autumn, and 108.3 ± 67.0 μg/day in winter. Multivariate analysis showed that age, body surface area, eGFR, and genetic subtypes affected basal warfarin maintenance dose (p < 0.05). Furthermore, except seasonal variation in vitamin K intake, no other factor affected PT-INR fluctuation or the necessity of adjustment of warfarin dose.

Conclusion:
Age, body surface area, eGFR, and genetic subtypes affected basal maintenance warfarin dose; however, except vitamin K intake, no other factor affected warfarin dose fluctuation.