bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 130: Effects of Genetic Inactivation of Amyloid Precursor Protein in Cerebral Microvasculature
Authors: Santhanam Anantha Vijay R , Austin Susan A , d'Uscio Livius V , Katusic Zvonimir S
Published: March 2022

Background:
Amyloid precursor protein (APP) is expressed in neuronal and non-neuronal tissues in the brain, including cerebrovascular endothelium. However, the physiological role of APP in cerebral vasculature is not completely understood. The present study was designed to determine the effects of inactivation of APP in cerebral microvasculature.

Methods:
Effect of genetic inactivation of APP was studied both
in vitro
and
in vivo
. Cultured human brain microvascular endothelial cells (hBMECs) were incubated with APP-siRNA
in vitro
, while control-siRNA treated hBMECs served as controls. To study the effect of genetic inactivation of APP
in vivo
, cerebral microvessels were obtained from APP-deficient (APPKO) mice. Cerebral microvessels from wild-type (C57BL/6) littermates served as controls.

Results:
Silencing APP expression in hBMECs resulted in selective reduction in endothelial nitric oxide synthase (eNOS) expression (P<0.05, n=6), while expressions of inducible NOS and prostacyclin (PGI2) synthase remained unchanged. Furthermore, loss of APP in hBMECs resulted in significantly increased production (P<0.05, n=5) of superoxide anions, as determined by quantitation of 2-hydroxyethidium from dihydroethidium using HPLC. In line with the results obtained from
in vitro
studies, cerebral microvessels of APPKO mice also demonstrated increased production of superoxide anions. Furthermore, levels of cGMP, second messenger of endothelial NO, were significantly attenuated in cerebral microvessels of APPKO mice, while levels of cAMP remained unchanged.

Conclusions:
Our results suggest that genetic inactivation of APP results in oxidative stress and impairment of endothelial NO signaling. We speculate that APP exerts vascular protective effects in the cerebral circulation under physiological conditions.
Abstract 139: Acute Stroke Reperfusion Therapy Trends in the Expanded Treatment Window Era
Authors: Asaithambi Ganesh , Tong Xin , George Mary G , Tsai Albert W , Peacock James M , Luepker Russell V , Lakshminarayan Kamakshi
Published: March 2022

BACKGROUND:
The American Heart Association/American Stroke Association (AHA/ASA) recommended an expansion of the time window for acute ischemic stroke (AIS) reperfusion with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) from 3 to 4.5 hours after symptom onset. We examined rates of IV and intra-arterial (IA) reperfusion before and after the recommendations to track guideline adoption in community practice.

METHODS:
Patients with AIS in the Paul Coverdell National Acute Stroke Registry spanning years 2007 to 2012 were identified. Trends in rates of IV rt-PA versus IA therapy were examined. Outcomes studied included symptomatic intracerebral hemorrhage (sICH), in-hospital mortality, ability to ambulate at discharge, and discharge destination.

RESULTS:
From 2007 to 2012, there were 182,235 AIS patients (median age 72 years, 51.5% women) in the database. AIS patients receiving IV rt-PA increased significantly from 3.7% in 2007 to 5.1% in 2012 in the ≤ 3 hour time window and from 0.2% in 2007 to 1.3% in 2012 in the 3-4.5 hour time window (p<0.001 for both). There was also a significant increase in rate of IA therapy between 2007 and 2012 from 0.5% to 1.9% (p<0.001). There was a significant decrease in the rate of sICH among patients who received any reperfusion therapy between 2007 and 2012 (p=0.003).

CONCLUSION:
There was increased utilization of IV rt-PA in the 3-4.5 hour time window from 2007 to 2012, which is likely from guideline recommendations from the AHA/ASA. This increase was associated with an increase in IA treatment rate along with a decrease in overall sICH rates for patients receiving any reperfusion therapy.
Abstract 144: The Pittsburgh Outcomes After Stroke Thrombectomy (POST) Score Predicts Good Outcomes After Endovascular Therapy for Anterior Circulation Large Vessel Occlusions
Authors: Rangaraju Srikant , Liggins John T , Aghaebrahim Amin , Streib Christopher , Sun Chung-Huan , Gupta Rishi , Nogueira Raul , Frankel Michael , Mlynash Michael , Lansberg Maarten , Albers Gregory , Jadhav Ashutosh P , Jovin Tudor G
Published: March 2022

Background:
Independent predictors of good outcome following large vessel occlusions (LVO) include age, infarct volume, NIHSS at presentation and revascularization status. The aim of this study was to develop an easy-to-use tool to predict good outcome following endovascular treatment for LVO.

Methods:
In a derivation cohort of patients with anterior circulation LVO treated with endovascular therapy at Grady Memorial Hospital (GMH, n=247), we performed logistic regression to identify independent predictors of good outcome (mRS 0-2 at 90 days). Factors were weighted based on B-coefficients to generate a score (POST) that predicts good outcome. The derivation cohort was divided in risk group quartiles and correlation analysis between predicted and observed rates of good outcomes was performed. POST was also validated in two cohorts derived from the University of Pittsburgh Medical Center (UPMC, n=380) and the DEFUSE 2 database (n=105).

Results:
In the derivation cohort (mean age 66±1 yrs, median NIHSS 18), independent predictors (p<0.2) of good outcome included final infarct volume (FIV; OR 0.97, 0.96-0.98), age (OR 0.96, 0.94-0.98), NIHSS at presentation (OR 0.93, 0.88-0.98) and PH1/PH2 hemorrhage (H; OR 0.3, 0.06-1.6, p=0.15). POST was defined as Age + 0.5 X FIV + 15 X H. Patients in the lowest POST quartile (<60) had a 91% chance of good outcome as compared to 3% in the highest POST quartile (≥120). There was a strong correlation between predicted and observed rates of good outcomes in the 4 groups (R=0.99, p<.001). POST performed well in predicting good outcomes in the derivation (AUC=0.85), as well as the UPMC (AUC=0.81) and DEFUSE 2 (AUC=0.86) validation cohorts.

Discussion:
The POST score is a validated tool to predict good clinical outcomes following endovascular therapy in patients with acute large vessel occlusions. This tool can guide families and physicians in clinical decision making following endovascular therapy.
Abstract 149: A Novel Phase 1/2A Study of Intraparenchymal Transplantation of Human Modified Bone Marrow Derived Cells in Patients with Stable Ischemic Stroke
Authors: Steinberg Gary K , Kondziolka Douglas , Schwartz Neil E , Wechsler Lawrence , Lunsford L. D , Coburn Maria L , Billigen Julia B , Keren-Gill Hadar , McGrogan Michael , Case Casey , Mori Keita , Yankee Ernest W
Published: March 2022

Introduction:
No treatment exists to restore lost brain function after stroke. Animal studies demonstrate that brain transplantation of SB623, a human bone marrow derived stromal cell with transient transfection of Notch-1 gene, after experimental stroke can improve neurologic outcome. This clinical study is the first North American trial of intraparenchymal transplantation of bone marrow derived cell therapy for chronic stroke patients.

METHODS:
This is a two center (Stanford University and the University of Pittsburgh) open label safety and dose escalation feasibility study. Stereotactic transplantation is targeted to the subcortical peri-infarct area. Inclusion criteria include 18-75 yo, 6-60 mos post subcortical MCA ischemic stroke, mRS 3-4 and NIHSS > 7. Safety endpoints include WHO toxicity scale, MRIs and clinical follow-up to 2 years. The primary efficacy endpoint is European Stroke Scale (ESS) at 6 mos; secondary efficacy measures are ESS, NIHSS, Fugl-Meyer, mRS, cognitive scores up to 2 years, and FDG-PET at 6 months.

RESULTS:
Seventeen patients have been treated (6 with 2.5M cells, 6 with 5M and 5 with 10M). Follow-up is currently 6 mos in 12 pts, 9 mos in 9 pts and 12 mos in 6 pts. There were 3 serious adverse events related to the surgery, but not to the cells (seizure, subdural hematoma, pneumonia). Cytokine levels, HLA antibody levels, and PBMC function did not change from baseline. Three measures of efficacy (NIHSS, ESS, Fugl-Meyer) all show a trend toward improvement. Since the sample size is small, no statistical analysis has been done. Two patients showed remarkable improvement in their motor (2) and language function (1) within 24 h of surgery, effects which have been sustained during follow-up (12 and 3 mos). These were the only 2 patients with new FLAIR lesions (DWI neg) in the motor cortex that resolved at 2 mos.

CONCLUSIONS:
Intraparenchymal transplantation of human modified bone marrow derived stromal cells in chronic stroke patients is safe, feasible, and shows a trend toward neurologic improvement. Larger studies will be initiated to further assess clinical efficacy.
Abstract 153: Motor Imagery During Movement Activates the Brain More Than Movement Alone After Stroke
Authors: Dodakian Lucy , Stewart Jill C , Cramer Steven C
Published: March 2022

Introduction:
Task-oriented training is a key component of many stroke rehabilitation programs. Motor imagery activates movement execution circuits as well as brain areas related to cognitive aspects of movement training, such as planning or functional relevance. Movement execution and imagery might work synergistically in activating the motor system after stroke, but to date have only been studied separately. The current study examined the neural correlates of imagery in conjunction with execution, hypothesizing that the combined approach would increase brain activation in areas important to movement training.

METHODS:
Seven patients with chronic right hemiparetic stroke were studied, with age 55.1±.3 years (mean±SD), 13.1±12.8 mo post-stroke, and arm motor Fugl-Meyer score 50.9±11.9. Each performed a paretic arm pronation/supination task under 2 conditions during functional MRI: [1] Movement execution task: subjects were instructed to pronate/supinate the arm in response to a visual cue. [2] Movement execution+imagery task: subjects were instructed to pronate/supinate the arm in response to the visual cue, but in addition were told to imagine that these movements were being performed to open and close a doorknob. fMRI analyses used SPM8 with threshold p<0.001 (uncorrected for multiple comparisons).

RESULTS:
For each condition, significant activation was present within the expected motor network, including left sensorimotor cortex and right cerebellum. Activation was significantly greater during performance of the movement execution+imagery task, compared to the movement execution task, within the left inferior parietal lobule and the right dorsolateral prefrontal cortex. No brain region showed greater activation during the movement execution task compared with the movement execution+imagery task.

CONCLUSIONS:
The movement execution+imagery task preferentially activated inferior parietal lobule and dorsolateral prefrontal cortex, regions that support goal-directed, complex movements. The addition of motor imagery to movement may provide a practical, accessible way to modulate activity in both the planning and the execution components of the motor network, and thereby further promote motor recovery after stroke.
Abstract 160: Spetzler-Martin Grade and Outcomes by Randomization Assignment in ARUBA
Authors: Mohr J. P , Parides M. , Moquete E. , Moy C. S , Vicaut E. , Moskowitz A. J , Hartmann A. , Stapf C. ,   for the international ARUBA investigators
Published: March 2022

Objectives:
To determine the predictability of the Spetzler-Martin Grade (SMG) with occurrence of hemorrhage in the ARUBA trial medical management arm compared with the interventional arm.

Methods:
Of the 223 patients enrolled in “A randomized trial of unruptured bAVMs” (ARUBA), 114 were allocated to medical therapy alone (MM), 109 to medical therapy with intervention (IT). The primary outcome is the composite endpoint of death or symptomatic stroke. The aim was to compare the relative frequency of primary outcome events between study arms depending on SMG scores at baseline.

Results:
For all but 2 patients (without catheter angiography) SMG scores at baseline are available for analysis. More than half of the cohort scored SMS-1 or SMS-2. After 33.7 months of follow-up, the intention-to-treat analysis showed primary outcome events were similarly distributed for bAVMs scored SMG-1 and SMG-4, but events were significantly less frequent in the MM arm for SMG-2 (7.4%) and SMG-3 (8.8%) as compared to IT (34.1%, p=0.011 and 57.1%, p<0.001, respectively). There was no trend toward increasing outcome events in IT with increasing SMG. The disparities were also found in in the as-treated analysis (see Table).

Conclusion:
AlthoughSMGhas long use for prediction of risk for surgical intervention, less success has been met with its use as a predictor of hemorrhage in a population not undergoing intervention,[i] And until ARUBA the SMG has not been tested in a trial. Our data to date suggest the SMG is neither a reliable predictor of risk for hemorrhage, nor indicative of increase in outcome risk with increasing grade. The later outcome for those in the ARUBA trial awaits further follow-up.

[i] Hartmann A, Mast H, Choi JH, Stapf C, Mohr JP. Treatment of arteriovenous malformations of the brain. Curr Neurol Neurosci Rep. 2007 Jan;7(1):28-34.
Abstract 161: Effects of Radiation Dose on Gene Expression in Cultured Murine Brain Endothelial Cells
Authors: Raoufi-Rad Newsha , Ukath Jaysree , Stoodley Marcus Andrew
Published: March 2022

Brain arteriovenous malformations (AVMs) are direct connections between arteries and veins that allow high pressure arterial blood to flow into fragile cerebral veins. AVMs are the leading cause of hemorrhagic stroke in children and young adults. Treatment of large and deep AVMs is challenging; new treatment methods are required. It is proposed that stereotactic radiosurgery could be used to selectively alter the AVM endothelial cell phenotype, allowing targeted molecular therapies which stimulate thrombosis.

We have previously shown that irradiation of endothelial cell cultures with 25Gy results in up-regulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In this study we hypothesise that a lower dose of radiation is similarly effective at causing up-regulation in ICAM-1 and VCAM-1 expression. Murine brain endothelial cell cultures were irradiated with 15Gy (n = 4) or 25Gy (n = 4) using a linear accelerator; non-irradiated cells were used as controls (n = 4). The relative gene expression at 96, 120, 144 and 168h after radiation was measured by quantitative real-time PCR. Genes encoding for ICAM-1 and VCAM-1 were found to be significantly up-regulated post-radiation with either 15Gy or 25Gy (p <0.001). Maximum gene expression of ICAM-1 and VCAM-1 was observed at 144h (7-fold) and at 120h (23-fold), respectively. There was no significant difference between the two doses. These results support the hypothesis that a 15Gy dose is as effective as a 25Gy dose. Therefore a lower dose of radiation might be equally effective at causing changes in endothelial cell phenotype. This is important from a clinical perspective because lower doses of radiation will be safer for the treatment of large AVMs.
Abstract 164: Comparison Between Transcranial Doppler and Functional MRI With Breath Holding Test for Cerebral Vasoreactivity Assessment in Patients with Carotid Stenosis
Authors: Campos-Herrera Cynthia R , Beltramini Guilherme C , Avelar Wagner M , Lima Fabricio O , LiMin Li ,   for the Vascular Neurology Study Group of UNICAMP
Published: March 2022

Background:
Impaired cerebral vasoreactivity (CVR) detected by Transcranial Doppler (TCD) is predictive of stroke in patients with carotid stenosis. Functional MRI (fMRI) can evaluate CVR either. Few studies have compared both methods for CVR assessment already. However, none of them used breath holding test (BHT) as the vasodilatory stimulus.

Objectives:
To assess CVR through BHT using TCD and fMRI in patients with carotid stenosis and controls in order to verify whether fMRI can detect any difference on BOLD-signal intensities between these groups. Additionally, we aimed to verify if fMRI can discriminate correctly any subject with impaired CVR as compared to TCD.

Methods:
Fifteen patients with carotid stenosis defined as stenosis ≥50% by angiography or ≥70% by ultrasound or ≥70% by CTA or MRA (11men;52-90yo;mean:67.7yo) and 7 matched-controls (5men:51-85yo;mean:64.6yo) performed BHT during TCD. Impaired CVR was diagnosed if mean percentage increase of MCA velocities ≤31% on 3-consecutive intervals of 30s of apnea intercalated by 4-minute-interval of normal breathing. During fMRI, BHT was performed using a traffic lights-based code for instruction on when it was time to stop breathing and was composed by 3-consecutive intervals of 24s of apnea intercalated by 4-minute-intervals of normal breathing. BOLD-signal intensity was measured in the lentiform nucleus ipsilateral to the carotid stenosis. In controls, the mean signal intensity of both lentiform nuclei was considered.

Results:
Patients and controls showed significantly different BOLD-signal intensities (p:0,0053). Based on CVR defined by TCD, there was an agreement between TCD and fMRI of 6/7 (85,7%) in controls, 11/15 (73.3%) in patients, and 17/22 (77,2%) overall.

Conclusion:
fMRI showed different BOLD signal intensities in patients and controls using BHT as the vasodilatory stimulus for CVR assessment. Additionally, there was a good agreement between fMRI and TCD on detecting patients with impaired CVR. Further studies are needed to evaluate whether impaired CVR on fMRI with BHT is predictive of stroke in patients with carotid stenosis, but these results suggest that fMRI may be a potentially useful tool for stroke risk assessment in clinical practice.
Abstract 166: Carotid Artery Stent Placement and Carotid Endarterectomy in Patients with Dialysis Dependent Renal Failure
Authors: Adil Malik M , Saeed Fahad , Qureshi Adnan I
Published: March 2022

Background:
Patients with dialysis dependent renal failure (DDRF) have a high prevalence of carotid artery stenosis. These patients are excluded from clinical trials evaluating carotid artery stent placement (CAS) and carotid endarterectomy (CEA).

Objective:
To identify differences in demographic and clinical characteristics and outcomes related to CAS and CEA in DDRF and non DDRF patients in a large national cohort.

Methods:
We determined the frequency of CAS and CEA performed in DDRF and non DDRF patients and associated in-hospital outcomes using data from the Nationwide Inpatient Survey (NIS) data files from 2005 to 2011. All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis.

Results:
Of the 8148 patients who underwent CAS, 693 (8.5%) were DDRF patients. After adjusting for age, gender, race, presence of dyslipidemia, congestive heart failure, and hypertension CAS performed in DDRF patients was associated with higher rates of in-hospital mortality(OR 3.7, 95% CI 1.0 - 13.9)(p=0.04) and moderate to severe disability (OR 1.7 , 95% CI 1.0 - 3.3)(p=0.05). Of the 43875 patients who underwent CEA, 3888 (8.8%) were DDRF patients. After adjusting for age, gender, race , presence of hypertension, congestive heart failure, dyslipidemia, nicotine dependence and alcohol abuse, CEA performed in DDRF patients was associated with higher rates of in-hospital mortality(OR 4.3, 95% CI 2.1 - 9.0)(p=<.0001) and moderate to severe disability (OR 1.4 , 95% CI 1.1 - 1.8)(p=0.009).

Conclusions:
Both CAS and CEA were associated with higher rates of in-hospital mortality and moderate to severe disability in DDRF patients.
Abstract 170: Aspirin Reduces Mortality Caused by Intracranial Aneurysm Rupture in mPGES-1 Deficient Mice
Authors: Pena SIlva Ricardo A , Kung David , Mitchell Ian J , Faraci Frank M , Heistad Donald D , Hasan David
Published: March 2022

Inflammation plays an important role in formation and rupture of intracranial aneurysms. Prostaglandin (PG) E2, a by-product of microsomal prostaglandin E2 synthase (mPGES)-1, is associated with inflammation and cerebrovascular dysfunction. We hypothesized that mPGES-1 deficiency protects against rupture of intracranial aneurysms. Intracranial aneurysms were induced in mPGES-1 knockout (KO) and wild-type (WT) mice with DOCA-salt hypertension and an intracranial injection of elastase. Systolic blood pressure and water intake (1% saline) was similar in WT and mPGES-1 KO mice. All WT mice survived 3 weeks after surgery and did not develop signs of subarachnoid hemorrhage (SAH). The majority of WT mice [73% (8/11)] developed aneurysmal dilatations in the cerebral arteries without evidence of SAH. In contrast, half of mPGES-1 deficient mice died or showed signs of SAH during follow-up (P<0.05). Postmortem analysis showed SAH in 56% (9/16) of mPGES-1 deficient mice. Unruptured aneurysms with no evidence of SAH were found in 25% (4/16) of mPGES-1 deficient mice. Subcutaneous infusion of PGE2 (1 mg/kg/d) to mPGES-1 KO mice did not appear to attenuate mortality or intracranial aneurysm rupture (p>0.05). Another group of mPGES-1 KO mice were treated with aspirin (6 mg/kg/d) or vehicle (water) by gavage since day 2 after surgery. Mortality caused by symptomatic aneurysm rupture was significantly reduced in aspirin (25% (3/12) vs vehicle (58% (7/12)) treated mPGES-1 KO mice (P<0.05). In conclusion, we found that genetic deficiency of mPGES-1 is associated with increased aneurysm rupture (p<0.01) and mortality (p<0.05) in a mouse model of intracranial aneurysms. Aspirin treatment significantly reduced mortality in mPGES-1 KO mice (P<0.05). Therefore, mPGES-1 and aspirin appear to play a protective role against rupture of intracranial aneurysms in mice.
Abstract 172: Circulating Mirna Profiles Discriminate Stroke Severity Associated With Age and Sex
Authors: Selvamani Amutha , Wright-Williams Madison H , Miranda Rajesh C , Sohrabji Farida
Published: March 2022

Background:
Age and sex have significant effects on stroke outcomes, however, the precise mechanisms by which these factors affect stroke pathophysiology remains unclear. Small non-coding RNA (miRNA) found in circulation have been used successfully as biomarkers and mechanistic targets for chronic and acute diseases. The present study investigated the impact of age and sex on microRNA expression following ischemic stroke.

Methods:
Adult (6 mo) and middle aged (11-12 mo) female and male rats were subject to middle cerebral artery occlusion (MCAo) using Endothelin-1. Blood samples were drawn at 2d and 5d post stroke. All animals were terminated at 5d and the brains processed for infarct analysis by standard histological procedures. Total RNA isolated from serum was subject to QPCR amplification for serum microRNAs (168) and 7 reference microRNAs (Exiqon focus panels). Normalized miRNA values were analyzed by Genesifter program using a two-way ANOVA with Benjamini and Hochberg corrections for false discovery rates..

Results:
Normalized infarct volume was significantly smaller in adult females (0.12+) as compared to middle-aged females (0.4; p<0.05), young males (0.51 ) or middle aged males (0.51. p<0.05). At 2d post stroke, 30 circulating miRNAs were differentially regulated and principal component analysis (PCA) confirmed that most of the variance was due to age. At 5d post stroke, 79 circulating miRNAs exhibited significantly different regulation, and PCA indicated that most of the variance was associated with sex. A small cohort (5) of miRNAs, miR-15a, -19b, -32, -136 and -199a-3p were found to be highly expressed in adult females compared to middle aged females, adult and middle-aged males. Predicted and experimentally validated gene targets for these 5 miRNAs analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that the top 10 KEGG pathways (high p values, large gene numbers) were related to growth factor signaling, cell structure and MAPK signaling.

Conclusion:
Overall, the pattern of circulating miRNA expression suggests an early influence of age in stroke pathology, with a later emergence of sex as a factor for stroke severity. Furthermore, a small cohort of miRNAs were found to discriminate severe and mild stroke infarction.
Abstract 180: The Relation of Timing and Degree of Blood Pressure Control with Hematoma Growth - Secondary Analysis of The Interact2 Trial
Authors: Stapf C. , Heeley E. , Delcourt C. , Arima H. , Chalmers J. , Anderson C. S
Published: March 2022

Background:
Acute blood pressure (BP) lowering therapy has shown clinical benefit in patients with acute intracerebral hemorrhage (ICH), but the effect of timing and degree of BP control on ICH growth has received less study.

Methods:
Among the INTERACT2 participants (N=2839) with acute ICH allocated either to intensive BP lowering therapy (IT, systolic target <140mmHg) or standard BP treatment (ST), CT brain imaging at baseline and 24 hours were centrally analysed in a subset of 491 (34%) in the IT and 473 (34%) in the ST groups.

Results:
Absolute mean ICH growth was lower in patients reaching BP target in <1h from randomization (1.7ml), as compared to those reaching target in 1-6h (4.2ml), and >6h (4.6ml, p=0.04). Hematoma growth was particularly high (14.4ml, 95%CI:10.0-18.8) in patients admitted with systolic BP>160mmHg who achieved <10mmHg systolic BP lowering over 24h, as compared to those achieving 10-20mmHg (3.7ml, 95%CI:0.3-7.1) or 20-30mmHg BP reduction (2.7ml, 95%CI:1.1-4.3); p<0.01). Patients maintaining target BP at 0-2 measurements over 24h had higher absolute volume increase (3.6ml; 95%CI:1.8-5.4) as compared to those who maintained target BP over 3-4 (1.6ml, 95%CI:-0.3-3.5), or 5-8 measurements (0.4ml, 95%CI:-1.7-2.4; p=0.01).

Conclusion:
These findings suggest that early and sustained BP control have favorable effects on hematoma growth. This reinforces the principle for patients with acute ICH to receive BP lowering therapy as early as possible and to achieve a lower level of systolic BP for the most favorable outcome.
Abstract 181: Meta-Analysis of Genome-Wide Association Studies Identifies Two New Susceptibility Loci for Intracerebral Hemorrhage
Authors: Woo Daniel , Falcone Guido J , Devan William J , Brown W. M , Biffi Alessandro , Anderson Christopher D , Deka Ranjan , Woo Jessica G , Martin Lisa J , Jagiella Jeremiasz M , Norrving BO , Jimenez-Conde Jordi , Urbanik Andrzej , Tirschwell David L , Selim Magdy , Silliman Scott L , Worrall Bradford B , Meschia James F , Kidwell Chelsea S , Montaner Joan , Fernandez-Cadenas Israel , Dichgans Martin , Greenberg Steven M , Rothwell Peter M , Lindgren Arne , Slowik Agnieszka , Schmidt Reinhold , Langefeld Carl D , Rosand Jonathan ,   International Stroke Genetics Consortium
Published: March 2022

Background:
Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar and non-lobar based on the location of the hemorrhage, with genetic variation contributing to risk of both subtypes. We report the first genome wide association study (GWAS) of this condition.

Methods:
The discovery phase included GWAS data (Illumina 610 or Affymetrix 6.0) from 6 ICH studies that enrolled subjects of European ancestry in the US and Europe. Cases were classified as lobar or non-lobar ICH based on head CT. ICH-free controls were selected from ambulatory clinics or by random digit dialing. Standard quality controls filters were applied and principal component analysis was used to account for population structure. Unobserved genotypes were inferred by imputation to 1000 genomes references panels. Association testing was carried out using logistic regression, assuming additive effects, and including age, gender and principal components in the model. Meta-analyses were completed using the inverse normal method, weighting by sample size. Replication of signals with p<1x10E-6 was pursued in an independent multi-ethnic study utilizing direct genotyping.

Results:
The discovery phase included 1545 cases (664 lobar and 881 non-lobar) and 1481 controls, and tested 5,358,103 SNPs. Two loci were identified: for lobar ICH, an intergenic region located on chromosome 12q21.1 (rs11179580: minor allele frequency [MAF] 0.22, OR 1.54, 95% CI 1.33 - 1.84; p = 6.7x10E-8); and for non-lobar ICH, a region on chromosome 1q22 encompassing the PMF1 and SLC25A44 genes (rs2984613: MAF 0.31, OR 1.45, 95% CI 1.2 - 1.64; p = 8.9x10E-9). Replication included 1256 cases (329 whites, 506 blacks and 421 Hispanics) and 760 controls (237 whites, 346 blacks and 177 Hispanics) and confirmed both loci: 12q21.1 (p = 0.037, meta-analysis p = 2.3x10E-8) and 1q22 (p = 3.0x10E-4, meta-analysis p = 2.2x10E-11).

Conclusions:
Two new susceptibility loci for ICH were identified, both showing location-specificity. These results confirm the presence of biological heterogeneity across ICH subtypes and highlight that different genetic risk factors may contribute to the small vessel diseases that underlie each ICH subtype.
Abstract 189: STAR: CT and MR Perfusion Imaging and Good Outcomes in Endovascular Stroke Treatment
Authors: Liebeskind David S , Scalzo Fabien , Johnson Mark S , Dávalos Antoni , Bonafé Alain , Castaño Carlos , Chapot René , Arnold Marcel , Sztajzel Roman , Liebig Thomas , Goyal Mayank , Besselmann Michael , Moreno Antonio , Schroth Gerhard , Gralla Jan , Pereira Vitor M , Nogueira Raul G ,   for the STAR Investigators
Published: March 2022

Background:
Perfusion imaging may be used to select stroke patients for endovascular treatment, although few data are available on studies of CT and MRI, as used in Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR), a prospective, multicenter, single-arm trial.

Methods:
The CT/MRI core lab processed available CT and MR perfusion source images with Olea Sphere 2.2 to measure volumes of infarct core and hypoperfusion. Established definitions for CT and MRI (core: rCBF < 31% (CT); ADC < 600х10
-6
mm
2
/s (MRI); hypoperfusion: Tmax > 6s (CT and MRI)) were used to provide equivalent measures. Core and hypoperfusion volumes, mismatch ratio and DEFUSE-2 categories of target and malignant profile were used to define the relationship of perfusion imaging with clinical outcomes.

Results:
87 of 202 cases in STAR (mean age 68.7 ± 12.5 years; 57% women; median baseline NIHSS 15 (8-25)) had CT (60/87 or 69%) or MRI (27/87 or 31%) perfusion imaging processed. This cohort was similar to other STAR cases with mean time to treatment of 263 ± 95 min and IV tPA before thrombectomy in 55%. Infarct core volume was mean 11.2 ± 19.7 (0-116.9) cc with hypoperfusion volume of mean 70.6 ± 46.0 (0-182.2) cc. Mismatch ratio was mean 17.8 ± 53.7. 75/87 (86%) cases were categorized as target mismatch and only 5/87 (6%) as malignant profile. 58/87 patients (67%) had a mRS of 0, 1, or 2 at 90 days and 39/87 (45%) with a mRS of 0 or 1. Multivariate logistic regression identified that age (OR 0.91, p=0.010), time to treatment (OR 0.23, p=0.001), and Tmax > 10 s volume (OR 0.96, p=0.003) were associated with good outcomes (mRS 0-2 at 90 days). Only 2/87 (2.3%) patients had symptomatic ICH. Target mismatch exhibited a trend for good outcomes (p=0.149).

Conclusions:
STAR enrolled subjects with small infarct cores and extensive mismatch, achieving good clinical outcomes in a majority of cases treated with endovascular therapy. Randomized trials using CT and MR perfusion imaging are warranted to assess the impact of current endovascular stroke treatments.
Abstract 19: Hospital Level Variation in Do-Not-Resuscitate Orders for Ischemic Stroke Patients: Implications for National Hospital Comparisons
Authors: Kelly Adam G , Zahuranec Darin B , Holloway Robert G , Burke James F
Published: March 2022

Background:
The Center for Medicare and Medicaid Services (CMS) plans to publicly report hospital-level adjusted ischemic stroke mortality as a marker of hospital quality. Do-not-resuscitate (DNR) orders, which are a well-known predictor of mortality after stroke, are not accounted for in the current CMS risk-adjustment model.

Methods:
Using the California State Inpatient Database from 2005-2011, ischemic stroke admissions (primary ICD-9 codes 433.x1, 434.x1, 436) over age 50 were identified. Cases were categorized by the presence/absence of a DNR order within the first 24 hours of admission. Multi-level logistic regression with a random hospital intercept was used to predict inpatient mortality after adjusting for comorbidities, vascular risk factors and demographics. Hospital mortality rank order was assigned based on this model and compared to the results of a second model that included DNR status.

Results:
From 356 hospitals, 261,921 cases were identified: 34,436 with early DNR (13.1%) and 227,485 without (86.9%). 43.1% of all mortality occurred in patients with DNR orders. Hospital-level utilization of DNR varied widely (quintile 1, 2.5% vs. quintile 5, 30.7%; p < 0.001). Compared to a model with DNR, a model not accounting for DNR overestimated mortality by at least 1% (absolute) in 36 hospitals (maximum change 2.4%) and underestimated mortality by at least 1% (absolute) in 15 hospitals (maximum change 1.8%). Failure to adjust for DNR orders resulted in substantial hospital reclassification across the rank spectrum (Figure).

Conclusions:
There is wide variation in the hospital-level proportion of ischemic stroke patients with DNR orders. To the extent variation in hospital-level DNR orders represents variation in patient preferences, CMS risk-adjusted mortality measures may result in hospital misclassification, and specifically punish hospitals treating a high proportion of patients who prefer lower intensity treatment.
Abstract 199: Antihypertensive Utilization in Hyperacute Intracerebral Hemorrhage Presenting to the Emergency Room
Authors: Flinders Abraham , Sanossian Nerses , Kim May A , Liebeskind David , Eckstein Marc , Stratton Samuel , Pratt Franklin D , Conwit Robin , Starkman Sidney , Saver Jeffrey L
Published: March 2022

Background:
There is wide variability in approaches to treating hypertensive primary intracerebral hemorrhage (ICH). We sought to characterize the types of antihypertensive agents and the rapidity with which these agents are utilized in a cohort of severely hypertensive (SH) ICH patients presenting to the emergency department (ED) <2 hours from symptom onset.

Methods:
Cases presenting to the ED via ambulance in the first 2 hours after symptom onset with intracerebral hemorrhage on initial imaging were identified from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 clinical trial of intravenous magnesium vs. placebo. All subjects provided consent in the field and were transported to their usual care hospital, and no guidance was provided on treatment. We defined SH ICH as having a SBP>180 at presentation.

Results:
Of 1700 stroke there were 369 (22%) cases with primary ICH and 220 cases (60%) of hypertensive ICH. They were evaluated in 53 separate EDs, with 175 cases (47%) at primary stroke centers (PSC). ICH cases had a mean [SD] age of 65 [13] years, 34% women, 79% White race, 34% Hispanic ethnicity, 80% pre-exisitng hypertension, 20% diabetes, 18% smokers; they were assessed in the field by paramedics a median [IQR] of 23 [15-40] and arrived in the ED 58 [46-77] minutes after onset. Overall 62% of ICH received antihypertensive (80% of ICH-SH, 39% ICH nonSH, p<0.001). Time in minutes from ED arrival to initiation of antihypertensive agent was 109 [SD160] in ICH-SH and 116 [SD198] in ICH-nonSH. Of the 214 who received antihypertensive therapy, 122 received short-acting/bolus therapy only, 70 continuous infusion only and 23 received both. The most commonly used short-acting/bolus therapy in the ED was labetalol in 111, hydralazine in 8, and enalapril in 5. The most commonly used continuous infusion was nicardipine (41), nitroprusside (35) and labetalol infusion (11). SBP was still elevated >180 in 37 (10%) At 4 hours after presentation. Time from ED to treatment was shorter at PSC EDs (73 vs. 144 minutes, p<0.001).

Conclusion:
There is wide variability in antihypertensive use among emergency departments in the studied geographic area. Despite high rates of treatment, there was a delay of 109 minutes in initiating therapy after ED arrival in ICH-SH.
Abstract 2: Extensive Collateral Recruitment after Intravenous Thrombolysis in Acute Ischemic Stroke is Associated with Symptomatic Intracranial Haemorrhage
Authors: yeo leonard , Paliwal Prakash , Teoh Hock Luen , Seet Raymond C , Chan Bernard P , Rathakrishnan Rahul , Ng Kay W , Bharatendu Chandra , Batra Amit , wakerley benjamin , ong jonathan , Ong Venetia H , Lim Gavin H , Ting Eric Y , Sharma Vijay
Published: March 2022

Background:
Various collateral channels are recruited to provide alternative pathways in acute ischemic stroke (AIS), however the relationship with patient outcomes remain unclear. We compared various existing methods of scoring collaterals on the pre-treatment and day-2 computed tomographic angiogram (CTA) of the brain in thrombolyzed AIS patients.

Methods:
We included 115 consecutive patients in whom CTA was performed both pre-tPA and on day-2. Intracranial collaterals were evaluated by 2 independent neuroradiologists using 4 existing and one modified method- Miteff’s system (grades middle cerebral artery (MCA) collateral branches with respect to sylvian fissure); Maas system (compares collaterals in affected hemisphere against the contralatral side); Modified Tan’s scale (collaterals in 50% or more of MCA territory classified as good); and 20-point collateral grading scale by Alberta Stroke Program Early CT score (ASPECTS) methodology. For the modified scoring system we adapted ASPECTS methodology into a 14 point score for cortical and internal cerebral veins (ICV) and removing basal ganglia area from scoring. Symptomatic intracranial hemorrhage (SICH) was defined by new bleeding on the CT scan and an increase in NIH stroke scale (NIHSS) by 4 points or more.

Results:
On univariate analysis collateral recruitment via the Tan scoring system, ASPECTS method (improvement of ≥6 points), modified scoring system (improvement ≥7 points), hypertension and higher NIHSS score were associated with SICH. On multivariate analysis only collateral recruitment on the Tan scoring system (OR 3.286 95% CI 1.014-11.025, p =0.049), Collateral recruitment on ASPECTS ≥6 points (OR 2.839 95% CI 1.064- 7.576, p = 0.037) and collateral recruitment on the modified scoring system ≥ 7 (OR 4.174 95% CI 1.212-14.372, p = 0.023) were independent predictors of SICH. Interestingly, collateral failure on the day-2 CTA did not show any association with SICH.

Conclusion:
Large recruitment of the collateral channels on the day-2 CTA is strongly associated with SICH after thrombolysis . Perhaps, an unregulated cerebral hyperperfusion contributed to SICH and close monitoring along with aggressive blood pressure control might prevent complications.
Abstract 20: Relationship Between Physician Annual Volume And Stroke Mortality - Results From the Ontario Stroke Registry
Authors: Fang Jiming , Stamplecoski Melissa , Hall Ruth , Bayley Mark , Silver Frank , Kapral Moira
Published: March 2022

Objective:
Previous studies have demonstrated an inverse relationship between hospital volume and stroke mortality. However, little is known about the effect of physician volume on stroke mortality.

Methods:
We used the Ontario Stroke Registry (OSR) to identify a cohort of stroke/TIA patients admitted to 11 regional stroke centers in Ontario, Canada (Jul 2003 - Mar 2008). The most responsible admitting physician was identified by linking the OSR data to the Discharge Abstract Database maintained by the Canadian Institute for Health Information. The risk of death after discharge was determined through linkages to the Ontario Registered Persons Database. Patients were divided into quintiles based on the annual volumes of the most responsible physicians. Multivariable analyses of physician volume effect were conducted using random effects hierarchical logistic regression models, adjusting for patient characteristics (sex, age, severity, stroke type, comorbidity and in-hospital care), physician characteristic (physician type, annual volume) and hospital characteristics (annual volume). Risk-adjusted mortality rates were calculated to determine if there was a threshold effect for physician volume.

Results:
There were 14,285 admitted stroke/TIA patients who were treated by 783 physicians. Physician volume had an inverse relationship with in-hospital mortality and 30-day mortality (p<0.0001). Risk-adjusted rates are shown in Figure.

Conclusion:
Higher physician annual volume is associated with lower stroke mortality at the regional stroke centers (average volume: 180~370 patients/year). A minimum annual volume of seeing stroke patients by admitting physicians should be recommended. Shifting the care of more stroke patients to high-volume physicians could potentially reduce mortality after stroke.
Abstract 201: Prevalence of Unsuspected Renal Insufficiency in Stroke Patients Presenting to the Emergency Department: A Population-Based Assessment
Authors: Grossman Aaron W , Khoury Jane C , Alwell Kathleen , Moomaw Charles J , Khatri Pooja , Woo Dan , Flaherty Matthew , Ferioli Simona , Mackey Jason , Martini Sharyl , de los Rios la Rosa Felipe , Kissela Brett M , Kleindorfer Dawn O
Published: March 2022

Background:
CT Angiography (CTA) provides timely information in patients with suspected acute ischemic stroke (AIS) or intracranial hemorrhage (ICH) regarding presence of arterial occlusion, vascular anomalies or ongoing hemorrhage. Although uncommon and typically transient, risk of contrast nephropathy can deter use of CTA in acute management of these patients, potentially delaying diagnosis and treatment. Using a nationally-representative, population-based epidemiologic database of patients with AIS and ICH, we determined the prevalence of chronic (CRI) and unsuspected renal insufficiency (URI).

Methods:
All patients with AIS and ICH who presented in 2010 to an emergency department within Greater Cincinnati / Northern Kentucky were included (n=2348). Charts were retrospectively reviewed, and characteristics including age, race, gender, hypertension (HTN), diabetes (DM), tobacco use, CRI, and serum creatinine (sCr) on presentation were abstracted. We determined the proportion of patients with CRI and those with URI (sCr ≥ 1.5 with no history of CRI). URI cases were further stratified as intermediate (sCr = 1.5-2.0) or severe (sCr > 2.0). Multivariable analysis determined independent predictors of URI.

Results:
There were 2049 AIS patients and 299 ICH patients in 2010. Overall, 409 patients had sCr ≥ 1.5 (17.4%) and 186 patients had sCr > 2.0 (7.9%). 348 patients reported CRI (14.8%). URI was noted in 166 patients (8.3% of those without CRI; 8.5% in AIS and 7.3% in ICH patients), and 40 patients had severe URI (2% of those without CRI). Independent predictors of URI included age (OR 1.13 per 5 years, 95% CI 1.06-1.20), HTN (OR 1.73, 95% CI 1.16-2.64), black race (OR 2.94, 95% CI 2.06-4.19), and male gender (OR 2.13, 95% CI 1.53-2.99).

Conclusions:
In our population, 17.4% of patients with AIS or ICH had an initial sCr ≥ 1.5. This elevation in sCr, high enough in many institutions to preclude CTA, was unsuspected in 8.3% of patients who had no history of CRI, and sCr > 2.0 was unsuspected in 2%. Predictors were as expected: age, HTN, black race and male gender. Estimates of CRI and URI among stroke patients should be considered, along with published rates and severity of contrast nephropathy, to guide future cost-benefit analyses of CTA in management of acute stroke.
Abstract 211: Subjective Judgments of Physicians and Nurses Are More Accurate Than Formal Clinical Scales in Predicting Functional Outcome After Intracerebral Hemorrhage
Authors: Hwang David Y , Dell Cameron A , Sparks Mary J , Watson Tiffany D , Langefeld Carl D , Comeau Mary E , Rosand Jonathan , Battey Thomas W , Koch Sebastian , Perez Mario L , James Michael L , McFarlin Jessica , Osborne Jennifer L , Woo Daniel L , Kittner Steven J , Sheth Kevin N
Published: March 2022

Introduction:
Providing an accurate prognosis is a fundamental responsibility of care providers for patients with intracerebral hemorrhage (ICH). The ICH and FUNC Scores are common clinical scales designed to predict functional outcome and mortality for ICH patients.

Hypothesis:
The ICH Score and FUNC Score have superior accuracy, compared to the early clinical judgment of physicians and nurses, with regards to the prediction of the Modified Rankin Scale (mRS) achieved by ICH patients at 3 months.

Methods:
We conducted a prospective study at 5 centers. For each consecutive adult patient admitted with primary ICH, one physician and one nurse on the treatment team were asked for prediction of mRS at 3 months. All predictions were collected within 24 hours of admission. ICH and FUNC Scores on admission and blinded outcome at 3 months were obtained for each patient, in part using data collected for the ongoing Ethnic/Racial Variations with ICH (ERICH) project. Predictive ability was measured by Spearman’s rank correlation (r).

Results:
For a total of 100 patients, 100 physicians (75 attendings, 25 trainees) and 100 nurses gave predictions. In order of strength of association with actual 3-month mRS, correlations were attending physicians r = 0.81, nurses r = 0.72, and trainees r = 0.66. Although suggestive, none of these groups were statistically superior (p > 0.10). However, nurses (p = 0.015) and attending physicians (p = 0.002), but not trainees (p = 0.57), were superior in their predictive ability over ICH Score (r = 0.55). Similarly, nurses (p = 0.0003) and attending physicians (p < 0.0001), but not trainees (p = 0.27), were superior over FUNC Score (r = -0.46). This accuracy advantage remained when examining predictions for (1) only those patients alive at 3 months (n = 65), and (2) only those patients for whom providers indicated that they would not recommend comfort care within the first 24 hours (n = 82).

Conclusions:
The ICH Score and FUNC Score did not have superior accuracy, compared to subjective clinical judgment, with regards to prediction of 3-month ICH outcome.