bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W MP35: The Re-examining Acute Eligibility for Thrombolysis Task Force Criteria for Defining Rapidly Improving Stroke Symptoms: A Pilot Prospective Study of tPA Treatment Decisions
Authors: Balucani Clotilde , Bianchi Riccardo , Weedon Jeremy , Levine Steven
Published: March 2022

Background:
Rapidly Improving Stroke Symptoms (RISS) is a controversial exclusion criterion for tPA for acute ischemic stroke (AIS). Prior studies suggest 4-44% of AIS patients eligible are not given tPA solely because of RISS and their outcome is not invariably benign. In 2013 The Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force published new criteria for defining RISS.

Objectives:
To estimate frequency and outcome of RISS based on TREAT criteria in a prospective cohort of consecutive AIS patients.

Methods:
Serial NIH Stroke Scales (NIHSS) for AIS patients admitted within 4.5 hrs of symptom onset were performed every 20 (±5) minutes until a treatment decision (tPA vs no tPA) was made, independent of the study. Improvement was calculated as the difference between baseline NIHSS (bNIHSS) and treatment decision NIHSS (tdNIHSS). Per TREAT criteria, RISS was defined as improvement to a non-disabling mild stroke and none of the following deficits present: complete hemianopsia; severe aphasia; visual or sensory extinction; any weakness limiting sustained effort against gravity; any total NIHSS >5; any remaining deficit considered potentially disabling by the patient and the treater. We compared frequency and outcomes of TREAT-based RISS with the most commonly used RISS definition [≥4 point improvement (4PI) on NIHSS]. Good outcome was defined as modified Rankin Scale of 0-1 at 3 months.

Results:
Fifty AIS were enrolled: mean age 65 yrs; median bNIHSS=5 (IQR 2,11); median tdNIHSS=5 (IQR 2,9); tPA was given in 23 (46%). Five/50 (10%) were RISS according to TREAT criteria, all 5 had good outcome at 90 days without tPA. Five/50 (10%) were RISS according to 4PI, and only 2/5 (40%) had good outcome while 1/5 (20%) died.

Conclusions:
This is the first preliminary, prospective estimate of RISS frequency and outcome according to TREAT criteria vs. a commonly used RISS definition. Our pilot data suggest the TREAT RISS frequency is in the lower end of prior retrospective estimates and, as a more restrictive definition, may better predict good outcome of RISS in future, larger studies.
Abstract W MP38: Resting-state Functional Connectivity after Aneurysmal Subarachnoid Hemorrhage
Authors: Maher Monica E , de Oliveira Manoel Airton Leonardo , Graham Simon , Macdonald R. Loch , Schweizer Tom A
Published: March 2022

BACKGROUND:
Up to 83% of aneurysmal subarachnoid hemorrhage (aSAH) survivors experience cognitive deficits - particularly in the domain of executive functioning, which encompasses skills necessary for everyday functioning. The neural correlates of these deficits have not yet been investigated. Resting-state functional magnetic resonance imaging (rs-fMRI) is an imaging technique to investigate functional connectivity between brain regions at rest - that is, without the use of a stimulation task. Spontaneous neural activity at rest is an intrinsic property of healthy brains and can be disrupted by various pathologies. In rs-fMRI, deviations from the norm (increases or decreases) are abnormalities indicative of the existence of impairments. HYPOTHESIS: We hypothesized that aSAH patients will exhibit altered resting-state functional connectivity within frontal brain networks that would map onto impaired performance on tests of executive functioning relative to matched healthy controls. METHODS: 14 aSAH patients and 11 healthy controls matched on age, education and gender were included. To differentiate between patients with good and poor cognitive outcome, a composite Executive Function score was generated using the z-scores of executive tests, and patients with negative composites were then classified as ‘Impaired’ for further analyses. RESULTS: The Impaired group scored significantly worse than both Controls and Unimpaired patients on 10 measures of executive functioning. Resting-state connectivity between the right dorsolateral prefrontal cortex (DLPFC) and the left superior frontal gyrus (SFG) was significantly increased in the ‘Impaired’ patients and this connection covaried significantly with composite executive scores. Increased connectivity between the left DLPFC and right precuneus was seen in the impaired patients relative to controls, covarying significantly with reduced mood scores. CONCLUSIONS: The aberrant connection between the right DLPFC and left SFG may underlie executive impairments after aSAH. This imaging modality could be explored as a potential diagnostic tool to identify cognitive impairment in aSAH patients and direct them to appropriate rehabilitation programs for improved cognitive outcomes.
Abstract W MP4: Stentriever Mediated Manual Aspiration Thrombectomy (SMAT) for Acute Ischemic Stroke in 93 Consecutive Patients
Authors: Jadhav Ashutosh P , Aghaebrahim Nima , Horev Anat , Giurgiutiu Dan Victor , Ducruet Andrew , Jankowitz Brian , Jovin Tudor
Published: March 2022

Background and Purpose:
Both stentriever technology and manual aspiration thrombectomy have been demonstrated to independently lead to high rates of recanalization in acute ischemic strokes presenting with large vessel occlusions. We sought to describe the safety and efficacy of a multimodal approach combining the two techniques.

Methods:
Retrospective review of a prospectively acquired acute endovascular stroke database.

Results:
93 consecutive patients were identified presenting between July 2013 and July 2014. Median age: 67. Median NIHSS: 17. Patients had the following baseline features: 48% female gender, 72% hypertension, 12% diabetes, 39% atrial fibrillation, 29% CAD. Occlusion distribution included 71% M1, 13% M2, 13% ICAT, 16% VB. On presentation, 28% received IV tpa and 34% presented beyond 8 hours. High quality recanalization (TICI2b/3) was achieved in 88% of patients. Recanalization required an average of 2.36 passes. The Solitaire stentriever was used in 81% of cases and the Trevo device was used in the remainder of cases. The aspiration catheter employed was the 072/058 Navien in 74% of cases, 043 DAC in 4% of cases and 5Max ACE in 27% of cases. Median door to groin puncture time was 69 minutes and median groin puncture to recanalization time was 47 minutes. Symptomatic hemorrhage occurred in 5% of patients. Good outcomes were noted in 42% of patients. In anterior circulation stroke patients who received IV tpa prior to IA therapy, good outcomes were noted in 50% of patients.

Conclusions:
SMAT is a safe and efficacious method of achieving rapid revascularization in acute stroke patients. Future prospective comparisons of MAT, stentreiver alone and SMAT are necessary to establish the most clinical effective therapy for acute thrombectomy.
Abstract W MP43: Platelet Testing is Associated With Worse Clinical Outcomes for Intracranial Aneurysm Patients Treated with the Pipeline Embolization Device
Authors: Brinjikji Waleed , Cloft Harry J , Lanzino Giuseppe , Hanel Ricardo , Siddiqui Adnan H , Kallmes David F
Published: March 2022

Objective:
Controversy exists as to whether platelet inhibition testing is necessary prior to aneurysm treatment in patients premedicated with antiplatelet agents. Using the IntrePED (
Int
ernational
Re
trospective Study of
P
ipeline
E
mbolization
D
evice) registry, we studied complication rates in platelet-testing and non-platelet testing groups to determine if platelet testing is associated with improved outcomes.

Materials and Methods:
Patients with unruptured intracranial aneurysms from the INTREPED registry were divided into those who received platelet testing (testing group) and those who did not (nontesting group). Morbidity, mortality and thrombotic and hemorrhagic complication rates were studied. Comparisons between groups for continuous variables were evaluated using
t
-tests and Fisher’s exact test or Pearson’s chi-square for binary categorical variables. Multivariate logistic regression analysis was performed to determine if platelet function testing was independently associated with poor outcomes adjusting for age, number of devices, aneurysm location, size, and use of multiple exchange wires.

Results:
When compared to the non-testing group, the platelet testing group suffered higher rates of ipsilateral intracranial hemorrhage (12/511, 2.3% versus 0/187, 0.0%, P=0.04), neurological morbidity (42/511, 8.2% versus 4/187, 2.1%, P=0.01), and combined neurological morbidity and mortality (45/511, 8.8% versus 6/187, 3.2%, P=0.01). More patients in the testing group were treated with multiple PEDs (228 patients, 38.1% versus 57 patients, 28.4%, P=0.01). On multivariate analysis, the platelet testing group had a higher odds of total major morbidity (OR=3.80, 95%CI=1.30=11.08, P=0.01) and total major morbidity and neurological mortality (OR=2.74, 95%CI=1.11-6.79).

Conclusion:
Our findings caution against blind acceptance of platelet testing in Pipeline patients. Further prospective studies are needed to determine if and when platelet testing in Pipeline patients is appropriate.
Abstract W MP44: Investigations Using a Combination of Computational Fluid Dynamics Technique and an Animal Model of Experimentally Induced Cerebral Aneurysms Suggest Important Roles of Wall Shear Stress on the Cerebral Aneurysm Development
Authors: Fukuda Shunichi , Shimogonya Yuji , Fukuda Miyuki , Hasegawa Koji
Published: March 2022

We have a series of reports suggesting that an increase in hemodynamic factors, especially wall shear stress, plays a central role in cerebral aneurysm development. We show here the effect of wall shear stress on the cerebral aneurysm growth, using computational fluid dynamics (CFD) analyses and an animal model of experimentally induced cerebral aneurysms.

3-dimentional CT angiographic images of 34 human cerebral aneurysms were used for CFD analyses. Measured flow rates derived from physiological data of individual patients, but not theoretically assumed rates, were used as inlet boundary conditions because there exists a significant influence of inlet boundary conditions between measured and theoretically assumed values on hemodynamics in human cerebral aneurysms as we reported previously. CFD analyses in human cerebral aneurysms frequently indicated an increase in wall shear stress at the aneurysm orifice. Moreover, if the arterial geometry around the aneurysm is virtually reconstructed just before the aneurysm induction by artificial removal of the aneurysm, the enhanced magnitude of wall shear stress and gradient oscillatory number was observed near the apex of arterial bifurcation where the aneurysm was removed.

In animal experiments, we examined the effect of blockage in the P2X4 purinoceptor, the vascular endothelial shear-sensor, on the frequency of aneurysm induction after aneurysm-inducing surgery, using P2X4 knockout mice (n=19) and wild type mice (n=21). The incidence of induced aneurysm formation in P2X4 knockout mice was significantly lower than in wild types (p<0.02). Immunohistochemical examinations indicated that the immunoreactivity of MCP-1, which is closely associated with inflammatory responses during aneurysm formation, was weaker in P2X4 knockout mice than in wild types.

These data suggest that during aneurysm formation, vascular endothelial cells might sense excessively high levels of wall shear stress over physiological limit, which may initiate damage to vascular components, leading to aneurysm development. A combination of CFD simulation in the human cerebral aneurysm and an animal model of experimentally induced cerebral aneurysms may be a good tool for the study of cerebral aneurysm formation.
Abstract W MP60: Prevalence Of Post Stroke Daytime Sleepiness
Authors: Ugdamina Fritzie R , Go Criscely , Navarro Jose C
Published: March 2022

Background of the study:
In patients with stroke, the most common Sleep Disorder are sleep apnea, insomia (30%), and excessive daytime sleepiness. Ischemic stroke patients had 76.8% sleep disorder and hemorrhagic stroke patients had 82.5% sleep disorder. There were several postulated mechanisms on the pathophysiologic effects of sleep disorders on stroke which includes: acute hemodynamic changes during episodes of apnea, decreased cerebral blood flow, and paradoxical embolization, hypercoagulability, hypoxia-related cerebral ischemia, and atherosclerosis. With these several mechanisms, post stroke recovery among patients with post stroke sleep disorder can be altered.

Methodology:
A cross sectional study was conducted in Jose Reyes Memorial Medical Center from July 2013 to June 2014. All Medical records and neuroimaging of post stroke patients (≥ 6 months) were reviewed. Those patients with cognitive dysfunction, unable to give consent or unable to understand the study protocol and whose neuroimaging cannot be retrieved were excluded in the study. The interviewer assisted Epworth Sleepiness Scale (ESS) was used in this study to determine daytime sleep propensity.

Results:
A total of 130 subjects were included. There were 82 (63%) male and 48(37%) female. The mean age is 58. The variables shown to be significantly associated with ESS were duration of stroke, number of risk factor and type of stroke. The more recent the stroke (specifically shorter than 2.7 years which is the mean), the higher the ESS score. A patient with two risk factors was 4.6x more likely to have an ESS of 10-14 compared to one who has only 1 risk factor. Those who had intracranial bleeding were 2.5 times more likely to have an ESS of 10-14.

Conclusion:
Among post stroke patients, the more recent the stroke, the more risk factors present, and those who had intracerebral hemorrhage have higher propensity for daytime sleepiness.
Abstract W MP71: Effect of Race/Ethnicity on Oral Anticoagulant-Associated Intracerebral Hemorrhage
Authors: Testai Fernando D , Mukarram Faisal , Culpepper Andre L , Sekar Padmini , Hillmann Maureen , Flaherty Matthew , Ringer Andrew J , Osborne Jennifer , Moomaw Charles J , Langefeld Carl , Woo Daniel
Published: March 2022

Background:
Oral anticoagulant (OAC) use is associated with poor outcome in intracerebral hemorrhage (ICH). The aim of this study was to determine if race/ethnic differences exist in this condition.

Methods:
Data were obtained from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study which is a prospective multicenter study of ICH. Exclusion criteria included missing initial hematoma volume or being on heparin or LMWH. Baseline and clinical characteristics, laboratory and imaging data at presentation and 24h, and mortality at 3 months were compared by OAC use and race/ethnicity. ANOVA was used to identify factors affecting initial hematoma volume by location and OAC use. Logistic regression was performed to evaluate risk of hemorrhage based on race/ethnicity.

Results:
A total of 2,020 of 2,276 cases met the inclusion criteria and were included in the analysis (627 whites, 739 blacks, and 654 Hispanics) of which 214 (10.5%) were on OAC (54% white, 22% black, and 23% Hispanic). History of hypertension, diabetes, hypercholesterolemia, previous stroke, and atrial fibrillation, elevated INR at admission, infratentorial location, and dementia were associated with OAC use (p<.001). There were no differences in initial hemorrhage volume by race/ethnicity. Among OAC users, median INRs were 2.10 (1.67-2.80) white, 1.89 (1.30-3.05) black, and 2.53 (1.60-3.60) Hispanic (p=0.06). Compared with whites, blacks on OAC were more likely to have deep hemorrhages (OR=1.5, 95%CI=1.2-1.9). Lobar ICH was less commonly seen in blacks (OR= 0.6, 95%CI 0.5-0.7) and Hispanics (OR 0.7, 95%CI 0.5-0.9). No differences were seen in infratentorial ICH. Use of OAC predicted higher case fatality at 3-months (OR=1.7, CI=1.1-2.6). In the subgroup analysis this association remained statistically significant for blacks only (OR=3.2, CI=1.4-7.0).

Conclusion:
In the largest prospective study in ICH we found that location and outcome in OAC-associated ICH differ among subjects of different racial/ethnic background. Our findings indicate that OAC-associated ICH is a heterogeneous condition and identifies blacks as a group with increased case fatality rate.
Abstract W MP81: A Door-to-Needle Time Under 30 Minutes Can Be Achieved and Can Improve Functional Outcomes
Authors: Whaley Michelle , Caputo Lisa M , Kozlowski Mark J , Fanale Christopher V , Wagner Jeffrey C , Bar-Or David
Published: March 2022

Background:
Improvements in functional outcomes are greatest when intravenous tissue plasminogen activator (IV-tPA) is administered immediately following acute ischemic stroke (AIS). Our study objectives were to describe interventions administered by our Comprehensive Stroke Center to improve door-to-needle (DTN) time, report median DTN times, and determine if interventions influenced functional outcomes and sICH rates.

Methods:
A DTN task force was created to streamline care of suspected AIS patients; interventions included developing a launch pad for emergent evaluation near registration staffed by a neurologist, physician and stroke program coordinator, transferring patients directly to CT room before entering an ED room, and giving IV-tPA in the CT room. We examined patients that received IV-tPA between 1/1/10 - 6/25/14 and compared median DTN times and discharge mRS over the study period using the Kruskal-Wallis analysis of variance. The chi-square trend test was used to compare proportions of patients receiving IV-tPA in less than 60 minutes.

Results:
During the study period 245 patients received IV-tPA. There was a significant decrease in median DTN times over time, from 46 minutes in 2010 to 29 minutes in 2014 (p=.001, Graph), and there was a significant trend towards shorter DTN times over time (p<.001, Graph). Additionally, discharge mRS significantly improved over time (p=.03). There was 1 case of sICH in 2010 and 2012.

Conclusions:
Streamlining initial evaluation of suspected AIS patients can reduce DTN times, and was also associated with improvements in functional outcomes at discharge. There was no change in sICH rates.
Abstract W MP85: Prostacyclin Receptor Activation With MRE-269 Reduces Infarct Size and Improves Long-term Neurological Recovery Following Ischemic Stroke in Both Young and Aged Rats
Authors: Yang Changjun , Alexander Jon C , DeMars Kelly M , Hawkins Kimberly E , Febo Marcelo , Candelario-Jalil Eduardo
Published: March 2022

Activation of the prostacyclin (PGI2) IP receptor is protective in brain ischemia. However, there is very limited information of the molecular mechanisms of protection and the feasibility to target this pathway in stroke. MRE-269, a highly selective PGI2/IP receptor agonist, has been recently discovered. This IP agonist has a long half-life in vivo and is currently in phase III clinical trials for pulmonary hypertension. We hypothesized that post-ischemic treatment with MRE-269 provides neuroprotection in a rat ischemic stroke model. Young male rats (3-4-month old) were subjected to middle cerebral artery occlusion (MCAO) for 90 min and treated intravenously with either vehicle (n=14) or MRE-269 (0.1, 0.25, 0.5, and 1 mg/kg, n=10-14/group) at the start of reperfusion. At 48 h post-MCAO, rats were sacrificed to determine infarct size, blood-brain barrier (BBB) damage (IgG extravasation), hemorrhagic transformation (brain hemoglobin levels), and matrix metalloproteinase (MMP)-9 activity. In a separate experiment, aged male rats (18-20-month old) underwent 90 min of MCAO and randomly selected to receive intravenously either vehicle (n=11) or MRE-269 (0.25 mg/kg, n=11) starting at 4.5 h post-MCAO. Additional doses were given every 12 h for the first 48 h, and then one injection daily for 7 days post-MCAO. The accelerating rotarod and the adhesive removal tests were conducted before and at 3, 7, 14 and 21 days after MCAO by an investigator blinded to treatment groups. Infarct volume was quantified by MRI at 48 h and 21 days post-MCAO. In young rats, MRE-269 dose-dependently reduced cortical infarct size. MRE-269-treated rats (0.25 mg/kg) had significantly reduced BBB damage and less hemorrhagic transformation. Compared with the vehicle group, MRE-269-treated animals showed a significant reduction in brain MMP-9 activity. In aged rats, MRE-269 treatment resulted in a significant long-term recovery in both locomotor and somatosensory functions following MCAO. Quantitative MRI data showed that MRE-269 significantly reduced infarct volume compared with vehicle-treated rats. Our data suggest that targeting the PGI2/IP receptor with MRE-269 is a novel strategy to reduce neurovascular injury and promote long-term neurological recovery in ischemic stroke.
Abstract W MP90: Suppression of Endothelial Cell Alpha5Beta1 Integrin Prevents Ischemic Stroke Injury in Mice
Authors: Roberts Jill , de Hoog Leon , Bix Gregory J
Published: March 2022

Although breakdown of the blood-brain barrier (BBB) leads to significant injury after ischemic stroke, therapies that target this breakdown have been unsuccessful in improving patient outcomes. We hypothesize that the α5β1 integrin, a receptor that is conditionally upregulated in brain endothelial cells following ischemic stroke, could play a critical role in worsening ischemic injury and functional outcome by contributing to BBB breakdown. To investigate this hypothesis, we performed transient CCA/MCA occlusion in endothelial cell specific α5 integrin knockout (α5 KO) mice and wild-type (WT) mice treated with a α5β1 small peptide inhibitor ATN-161. Following experimental stroke, while WT control mice showed significant TTC-visualized infarcts by post-stroke day (PSD) 3, α5 KO mice and WT mice treated with ATN-161 had minimal to no discernible infarcts. Cresyl violet neuronal stain further demonstrated little to no tissue disruption and neuronal injury on PSD 1-3 in the α5 KO stroked brains. Furthermore, the BBB remained intact in the stroked α5 KO mice as evidenced by absent IgG staining in the brain parenchyma which was otherwise abundant in stroked WTs. Likewise, several markers of BBB stability such as the tight junction proteins Claudin-5 and ZO-1 were found to be upregulated in the α5 KO mice after stroke. Importantly, α5 KO mice did not have any difference in cerebrovascular anatomy or collateral brain blood flow that could otherwise account for these results. Finally, in vitro assays of brain endothelial cells exposed to oxygen-glucose deprivation (OGD) demonstrated that ATN-161 could prevent OGD-mediated increased endothelial cell permeability as measured by TEER and FITC-dextran, and enhanced beneficial Claudin-5 rearrangement at the cell surface. Taken together, these results suggest that suppression of α5 integrin in brain endothelial cells conveys significant resistance to experimental ischemic stroke injury due, at least in part, to enhanced BBB stability, and suggest that α5β1 integrin represents a novel and very promising therapeutic target for stroke.
Abstract W MP93: Changes in FDG-PET Activity Following Intraparenchymal Injection of SB623 Cells in Patients with Stable Ischemic Strokes
Authors: Kenmuir Cynthia L , Reddy Vivek K , Mountz James , James Jeffrey , Steinberg Gary K , Kondziolka Douglas S , Lunsford L. D , Schwartz Neil E , Yankee Ernest , Wechsler Lawrence R
Published: March 2022

Background:
Ischemic stroke remains a major cause of disability with 90% of patients achieving no improvement after 90 days. The primary objective of this study was to evaluate the safety and feasibility of intraparenchymal administration of SB623 cells in chronic stroke. SB623 cells are adult bone-marrow-derived cells transfected with a plasmid encoding the intracellular domain of Notch-1 that have demonstrated improvement in functional testing in animal models of stroke.

Methods:
Patients with hemiparesis from stable subcortical ischemic stroke and NIHSS > 7 received intracranial injection of 2.5, 5 or 10 million SB623 cells. Clinical outcome measures included NIHSS, MRS, ESS and FMA measured at baseline and repeated at 6 and 12 months. FDG-PET was analyzed at each time point using cluster analysis within 5 regions of interest (contralateral frontal cortex, medial ventral to infarct, contralateral putamen, contralateral sensori-motor cortex, and contralateral thalamus).

Results:
Five patients enrolled at one academic center were included in this initial FDG-PET analysis. In these 5 patients, there was improvement in NIHSS (p = 0.008) and ESS (p = 0.006), which was most apparent from 0 to 6 months (p = 0.005; p = 0.005). There was also an increase in FDG-PET activity in the contralateral sensori-motor cortex from 0-6 months (p = 0.005), which was related to NIHSS, ESS and FMA (p = 0.043). Analyses of individual patients showed increased FDG uptake contralateral to the injection site in 3/5 patients. There was an increase near the area of infarct in 2/5 patients that was seen at 6 months but not at 12 months.

Conclusions:
Intraparenchymal injection of SB623 cells in chronic ischemic strokes resulted in increased FDG uptake predominantly in areas contralateral to stem cell injection in some patients. These increases were associated with improved clinical outcome measures suggesting that the PET changes might reflect activation of neural pathways due to stem cell therapy. Further PET studies with appropriate controls are warranted.
Abstract W MP98: Ethnic Differences in Stroke Quality of Care Between Mexican Americans and Non-Hispanic Whites: The BASIC Project
Authors: Zahuranec Darin B , Lisabeth Lynda D , Baek Jonggu , Adelman Eric E , Garcia Nelda M , Campbell Morgan S , Morgenstern Lewis B
Published: March 2022

Background:
Mexican Americans (MAs) have worse outcomes after stroke than non-Hispanic Whites (NHWs). We investigated ethnic differences in the quality of inpatient stroke care between MAs and NHWs to determine if quality differences may contribute to the observed outcome disparity.

Methods:
Cases of ischemic stroke were identified from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project (February 2009- June 2012). Quality of inpatient stroke care was assessed with seven quality metrics based on the 2008 Joint Commission Primary Stroke Center definitions. Two summary measure of overall quality were also created (binary defect-free care and a continuous composite score: proportion of achieved eligible measures). Multilevel generalized linear regression models were used to assess ethnic differences in quality of care, both unadjusted and then adjusting for hospital-level effects, demographics and confounders.

Results:
A total of 757 individuals were included (480 MAs and 277 NHWs). MAs were less likely than NHWs to receive tPA (RR: 0.71, 95% confidence interval (CI) 0.53, 0.96, p=0.026), and MAs with atrial fibrillation were less likely to receive anticoagulant medications at discharge (RR 0.71, 95% CI 0.55, 0.91, p=0.008). There were no ethnic differences in the other individual quality measures, or in the two overall summary measures. Adjustment for hospital clustering, demographics, and other confounders (summary measures only) resulted in little to no change in the association between ethnicity and quality (Table).

Conclusions:
There were no ethnic differences in the overall quality of stroke care between MAs and NHWs, though ethnic differences were seen in indicators for tPA and anticoagulant at discharge for atrial fibrillation. Since less than 20% of the population were eligible for these two measures, factors other than quality are likely to be primarily responsible for ethnic differences in stroke outcome.
Abstract W P100: Arginase-1 Is A Novel Biomarker Of Post-stroke Immune Suppression
Authors: Barr Taura L , Chantler Paul , Petrone Ashley , Brooks Steven , Frisbee Jefferson , Simpkins James
Published: March 2022

Objective:
Arginase-1 (ARG1) is a novel biomarker of vascular and immune responses in ischemic stroke (IS). The objective of this study was to determine the relationship between ARG1 peripheral blood gene expression, history of hypertension and IS recovery.

Methods:
Peripheral blood samples were collected from IS patients’ ≥18 years of age within 24 hours from symptom onset. Stroke severity was determined by the NIHSS. Diagnosis of hypertension and lymphocyte counts were obtained from medical record. Modified rankin scale (MRS) was used to determine 30 day recovery. RNA was extracted from Paxgene RNA tubes, amplified, and hybridized to Illumina HumanRef-8v2 bead chips. Gene expression was compared in a univariate manner between IS patients with good (MRS 0-1) and bad (MRS 2-6) outcome using t-test in GeneSpring. Inflation of type one error was corrected by Bonferroni.

Results:
Twenty-three IS patients were recruited. Most patients had cardioembolic (n=14; 41.2%) or large artery stroke (n=5; 14.7%). Median pre stroke MRS was 0; median baseline NIHSS was 3 (range 0-24); and median 30 day MRS was 0 (range 0-6). ARG1 was higher in stroke patients with a history of hypertension (p=0.021); and there was an inverse relationship between ARG1 and lymphocyte count. When controlling for age, NIHSS and hypertension, high baseline expression of ARG1 significantly predicted worse scores on the MRS. We conducted a pilot study in n=3 female rats undergoing middle cerebral artery occlusion. As expected, there is an increase in ARG1 expression in the peripheral blood at 2 hours after ischemia that decreases within 24 hours, similar to that which we see in our human IS population.

Discussion:
This preliminary data supports the hypothesis that mechanisms of ARG1 induced lymphocytopenia are altered by the presence of pre-existing cardiovascular disease and may play a role in post-stroke immune suppression. Future studies are required to determine the functional relationships between ARG1 and immune dysfunction and determine appropriate clinical interventions.
Abstract W P106: Pericyte Protection by Edaravone After Tpa Treatment in Rat Cerebral Ischemia
Authors: Deguchi Kentaro , Kono Syoichiro , Yunoki Taijun , Sato Kota , Ota Yasuyuki , Hishikawa Nozomi , Yamashita Toru , Abe Koji
Published: March 2022

i) Background & Objectives:
Pericytes play a pivotal role in contraction, mediating inflammation, and regulation of blood flow in the brain. In the present study, changes of pericytes in the neurovascular unit (NVU) were examined in relation to the effects of exogenous tissue plasminogen activator (tPA) and a free radical scavenger, edaravone.

ii) Methods:
Immunohistochemistry and Western blot analyses showed that the overlap between PDGFRβ-positive pericytes and N-acetylglucosamine oligomers (NAGO)-positive endothelial cells increased significantly at 4 days after 90 min of transient middle cerebral artery occlusion (tMCAO).

iii) Results:
The number of pericytes and the overlap with NAGO decreased with tPA, but recovered with edaravone 4 days after tMCAO with proliferation. Thus, tPA treatment damaged pericytes resulting in the detachment from astrocytes and a decrease in GDNF secretion. However, treatment with edaravone greatly improved tPA-induced damage to pericytes.

iv) Conclusion:
The present study demonstrates that exogenous tPA strongly damages pericytes and destroys the integrity of the NVU, but edaravone treatment can extremely ameliorate such damage after acute cerebral ischemia in rats.
Abstract W P111: Early At1 Blockade Ameliorates Ischemia/reperfusion Injury By Pi3k/akt And Enos Pathways: In Vivo And In Vitro Evidence
Authors: Ishrat Tauheed , Pillai Bindu , Somanath Payaningal R , Ergul Adviye , Fagan Susan C
Published: March 2022

Background & Objective:
We have recently shown a robust protection with Angiotensin (Ang) II type 1 receptor blockers (ARBs) against cerebral ischemia/reperfusion (I/R) injury. However, the mechanisms by which ARBs protect against I/R injury are still unclear. We tested the hypothesis that the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway mediates some of the protective effects of ARBs after I/R injury.

Methods:
Male Wistar rats (280-300 g) underwent transient middle cerebral artery occlusion (MCAO) for 90min followed by reperfusion and received intravenous injection of candesartan (1 mg/kg) or vehicle at the time of reperfusion. Additional four groups of candesartan were injected intracerebroventricularly with PI3K/Akt, MEK and p38MAPK inhibitors at 15 min before MCAO. Rats were sacrificed at 24h post-MCAO and brains perfused for evaluation of neurological deficits, infarct size, and protein expression. Oxygen and glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemic insult in hippocampal neuronal cells (HT22).

Results (Table):
Candesartan reduced infarct size and improved neurobehavioral outcomes in rats subjected to I/R. Candesartan alone increased phosphorylated eNOS, Akt and VEGF expression after I/R injury. Moreover, blockade of PI3K but not MEK or p28MAPK activity, compromised candesartan-induced protection. These findings provided the first evidence that candesartan improves eNOS phosphorylation in response to the activated PI3K/Akt signaling. In vitro studies further confirmed that candesartan protects against OGD/R-induced neuronal death through PI3K/Akt signaling stimulation in HT-22 cells.

Conclusions:
Our findings lead us to suggest that the PI3K/Akt pathway can play a role in mediating the protective effects of candesartan and provide therapeutic avenues for the treatment of stroke.
Abstract W P114: Pure Pontine versus Pontine Plus Infarction Assessed by Diffusion Weighted MRI: Etiological and Clinical Differences
Authors: Kim Nayoung , Kim Seung Min , Kim Jong S.
Published: March 2022

Pontine infarction is often associated with extrapontine infarcts. We aimed to elucidate differences in clinical characteristics and stroke mechanisms between the isolated pontine (IP) and pontine plus (PP) infarcts. We studied consecutively admitted patients with acute ischemic stroke (< 7 days after the symptom) occurring in the pons between 2004 and 2013. All patients were assessed by diffusion weighted MRI (DWI) and MR angiography. According to DWI findings, we divided the patients into the IP and PP groups. In addition, pontine lesions were categorized as upper, middle and low according the previous report (Kim JS et al. Stroke 1995). Lesions were also categorized as focal vs. extensive and unilateral vs. bilateral. Functional outcome was measured by modified Rankin scale (mRS) at discharge. There were 834 (504 male) patients, 675 in the IP group and 159 in the PP group. The most commonly involved extrapontine territory was the posterior inferior cerebellar artery territory (54.1%) followed by superior cerebellar artery territory (42.1%) and occipital lobe (35.2%). As compared to the IP group, the pontine lesions in the PP group were more often located in the rostral (upper (67.3%), middle (61.6%), upper plus middle (40.3%)) level (p < 0.001). Lesions involving more than 2 levels (40.3% vs. 10.5% p<0.001), extensive (20.8% vs. 2.7%, <0.001) and bilateral (37.1%, vs. 2.8%, p<0.001) infarcts were more frequent in the PP group. The PP group had a higher prevalence of symptomatic stenosis (26.7% vs. 72.2%, p<0.001), large artery disease (60.5% vs 25.9%) and cardioembolism (16.0% vs. 2.1%, <0.001) than the IP group. In multivariable analysis, atrial fibrillation (OR: 3.87, 95% CI: 2.16-7.08) was significantly associated with PP. mRS at discharge was higher in the PP than IP group (median 3 (IQR 2-5) vs. 2 (IQR 1-3), <0.001). PP groups have more extensive and rostral pontine lesions, and are more often associated with large artery artherosclerosis, cardioembolism, and worse functional outcome. Prevention and therapeutic strategies should differ between the two groups.
Abstract W P125: Telephone versus In-person Psychosocial Behavioral Treatment in Post-Stroke Depression
Authors: Kirkness Catherine J , Becker Kyra J , Cain Kevin C , Kohen Ruth , Tirschwell David L , Teri Linda , Veith Richard R , Mitchell Pamela H
Published: March 2022

Background:
We previously showed that a brief psychosocial behavioral intervention delivered in-person by advanced practice nurses was effective in reducing post-stroke depression (PSD).

Purpose:
This randomized clinical trial compared a shortened (6 week) intervention by telephone or in-person to usual care in volunteers within 4 months of an ischemic or hemorrhagic stroke.

Methods:
100 stroke survivors who screened positive for depression (Geriatric Depression Score >11) were randomized to usual care (UC), telephone intervention (TI), or in-person intervention (IPI). Primary outcomes were percent reduction in the Hamilton Depression Rating Scale (HDRS) at 8 weeks, 21 weeks and 12 months following study entry. Outcome assessors were masked to randomization status.

Results:
All three groups had similar depression scores at baseline (HDRS mean 18 for UC and TI, 19 for IPI). The mean percent reduction in HDRS scores for telephone and in-person groups was 42% and 40% immediately following the intervention at 8 weeks compared to a 30% reduction in the usual care group. However the difference only trended toward significance, controlling for age, with older age associated with better response (p = 0.31). There was a greater early reduction in depression in the UC group than in our previous work (30% HDRS reduction vs 18% at 8 weeks). By 21 weeks and 12 months following entry there was no significant difference between groups in HDRS reduction (40% UC, 40% TI, 39% IPI and 37% UC, 42% TI and 44% IPI, respectively).

Conclusions:
A brief psychosocial intervention for PSD reduced depression somewhat more than usual care (p=.31) right after treatment but the difference between groups was even less at 21 weeks and one year following entry. The reduction in depression was slightly smaller than in our earlier study for the intervention groups, and the usual care group improved more. The comparability of telephone and in-person follow-up and treatment for depression is important given mandated post-hospital follow-up for comprehensive stroke centers. The improved response to brief therapy for older participants suggests tailoring of care to provide individualized follow-up.
Abstract W P132: Poststroke Depression After Intracerebral Hemorrhage At Young Age
Authors: Koivunen Riku-Jaakko , Tatlisumak Turgut , Putaala Jukka
Published: March 2022

Background and Purpose:
Poststroke depression (PSD) is an important complication of stroke. We studied long-term PSD after intracerebral hemorrhage (ICH) at young age, as well as the quality of life of the survivors.

Methods:
We gathered clinical and imaging data on young ICH patients between age 16 and 49 treated in the Helsinki University Central Hospital between January 2000 and March 2010. The survivors were interviewed with structural questionnaires including Beck Depression Inventory II (BDI-II), Hospital Anxiety and Depression Scale (HADS), EuroQol (EQ-5D), Pain Anxiety Symptoms Scale (PASS-20), Brief Pain Inventory (BPI), and Montreal Congnitive Assessment (MOCA). Univariate analysis was performed to identify baseline factors associated with PSD (BDI-II score > 13). Correlation between degree of disability measured by modified Rankin Scale score and PSD was analyzed.

Results:
Median follow-up time was 9.7 [7.0-12.0] years. PSD was present among 30 (23.1%) out of 130 patients included. Mild or moderate emotional distress was present in 47 (36.2%) patients (HADS score > 7). Discomfort or pain was reported by 55 (42.3%) patients (measured by EQ-5D). Higher degree of disability was associated with symptoms of depression (higher BDI-II scores, p=0.001), and emotional distress (higher HADS scores, p=0.004). The only baseline factor identified to associate with PSD was hydrocephalus (p=0.014). Median PASS-20 score was 9 (IQR 0-25), median BPI score was 5 (0-23), and median MOCA score was 26 (22-28).

Conclusions:
One out of four survivors of ICH at young age suffers long-term PSD. Higher degree of disability predicted occurrence of PSD.
Abstract W P136: Aiding Stroke Rehabilitation with the Modified Atkins Diet: A Pilot Trial
Authors: Dohle Carolin I , Kennedy Juliana M , Goroff Holly L , Coar Patricia , Kossoff Eric H , Ratan Rajiv R
Published: March 2022

Introduction:
The Modified Atkins Diet (MAD) is a low carbohydrate, ketogenic diet. Animal studies suggest ketogenic diets enhance functional stroke recovery by activating transcriptional programs associated with brain protection and repair. The safety of use of the MAD in the elderly stroke population is however unknown. We here expand the use of MAD in a new patient population.

Setting:
Inpatient Stroke Rehabilitation Unit

Methods:
18 first time ischemic stroke patients were randomized to receive either the MAD or their respective regular diet. Laboratory studies were obtained upon admission and every 5 days until discharge. Functional outcome measures included the Upper Extremity Fugl Meyer Motor Score (FMMS), Functional Independence Measure (FIM) and Montreal Cognitive Assessment (MOCA). Urine was tested daily for presence of ketones. A registered dietician monitored patients daily. All patients received cholesterol-lowering medication.

Results:
10 patients received the MAD and 8 respective control diets. Age, gender, and interval post stroke did not differ significantly between groups. No significant difference existed between groups in admission cognitive, motor and total FIM scores, FMMS and MOCA scores. 4 patients withdrew prematurely from the MAD group due to low palatability of a pureed diet with nectar thick liquids. No significant medical events were encountered in either group. The MAD did not induce significant changes in LDL (-13.8±29.7 vs. -7.5±19.2;p=0.59), cholesterol (-9.2±36.5 vs. -10.8±25.22;p=0.92) and glucose levels (14±28.5 vs. -0.38±20.5;p=0.4).The MAD and Control group had similar changes in total (30.9,±12.3 vs. 25.9±11.9;p=0.5), motor (18.8±14.5 vs. 18.5±13.1;p=0.62), cognitive FIM (4.5,±2.3 vs. 5±3.5;p=0.4),FMMS(15.2±5.01 vs. 17.8±11.6;p=0.65),and MOCA scores (6.2±5.2 vs. 4.6±2.96;p=0.57).

Conclusion:
The Modified Atkins Diet is a safe and feasible intervention to aide stroke recovery. No adverse effects on lipid and glucose profile were noted, and the diet was overall well tolerated. A larger, multi-center trial will be needed to test for efficacy. The study also highlights the advantages of the rehab setting for implementing dietary interventions post stroke and verifying compliance.
Abstract W P142: White Matter Lesion Severity and Functional Recovery Following Inpatient Rehabilitation After Ischemic Stroke
Authors: Tanaka Makiko , Ito Taiji , Nakanaga Ayako , Sugiura Shiro , Shimizu Yoshiomi , Yoshikawa Kenji , Takahashi Tsutomu
Published: March 2022

Background and purpose:
Functional outcome after stroke mainly depends on the stroke severity. However, extent of functional recovery varies between individual patients of same degree of disability in stroke rehabilitation. The aim of this study is to investigate the association between white matter lesion (WML) severity and the extent of functional recovery following intensive rehabilitation after ischemic stroke.

Methods:
The study included patients who were moved to a rehabilitation unit within 2 months after onset of ischemic stroke. Patients with diagnosed dementia or patients with cognitive decline who needed care before stroke were excluded. The degree of WMLs, the location and size of stroke lesions were assessed using brain MRI performed in an acute phase. Separate visual ratings were made for the periventricular hyperintensities and deep white matter hyperintensities on FLAIR images. Functional status was measured using the Functional Independence Measure (FIM) when a patient was moved to a rehabilitation unit and at the time of discharge. Functional recovery was quantified by the change in FIM score (FIM gain). We retrospectively investigated the association between WML severity and FIM gain.

Results:
A total of 292 patients (166 men and 126 women, mean age 73.3 ± 9.8 years) were included in the study. The mean time interval between stroke onset and rehabilitation start was 35.0 days and the mean length of stay in the unit was 71.6 days. FIM gain was associated with age, stroke severity, functional status before stroke, lobar stroke lesions, and both periventricular and deep white matter hyperintensity scores. Infarct size was not significantly associated with FIM gain. On the other hand, deep white matter hyperintensity score was independently associated with lower FIM gain after adjusting for age, sex, timing of rehabilitation start, length of stay, functional status before stroke, and NIHSS score on admission.

Conclusion:
In patients with subacute ischemic stroke, severity of cerebral WMLs is an independent factor affecting functional recovery following intensive rehabilitation.
Abstract W P145: Increased Areas of Pericardial and Intrathoracic Adipose Tissue Predict Early Mortality or Recurrent Stroke and Reflect Systemic Inflammation in Patients With Ischemic Stroke
Authors: Muuronen Antti T , Korhonen Miikus , Taina Mikko , Pulkki Kari , Vanninen Ritva , Mustonen Pirjo
Published: March 2022

Introduction:
Chronic low-grade inflammation is a recognized risk factor for all cardiovascular diseases (CVD). Of different kind of adipose tissue located in the thoracic cavity the pericardial (PAT) but not intrathoracic adipose tissue (IAT) has been shown to associate with the risk of CVD.

Hypothesis:
We assessed the hypothesis that increased areas of both PAT and IAT are associated with systemic inflammation, early mortality, and recurrent stroke.

Methods:
A total of 162 patients (69 % men, mean age 61 years) with embolic stroke of undetermined or suspected cardiogenic etiology were studied. Areas of PAT and IAT were assessed by cardiac CT performed at the time of hospital admission. Plasma levels of Interleukin (IL-) 6, IL-1, IL-10, IL-18, tumor necrosis factor (TNF) and high sensitivity CRP were assessed three months after stroke. Follow-up data of mortality and recurrent stroke was collected up to five years after the first stroke.

Results:
Patients who encountered death (n=18) or recurrent stroke (n=25) during the follow-up time had larger PAT (14.5 cm2 vs 11.9 cm2, p=0.041) and IAT (30.9 cm2 vs 26.1 cm2, p=0.038) areas, and also had higher plasma levels of IL-6 (p=0.047). PAT and IAT areas were associated with plasma levels of IL-6 (r=0.251; p=0.042 and r=0.287; p=0.019, respectively).

Conclusions:
Patients who encountered either death or recurrent stroke during the five-year follow-up period had larger areas of PAT and IAT and higher plasma levels of IL-6 suggesting that both PAT and IAT, and contiguous systemic low-grade inflammation may have a role in the pathogenesis of embolic stroke of undetermined or cardiogenic origin.