bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2817: Simvastatin Reduced The Rupture Of Intracranial Aneurysms In Mice
Authors: Liang Elena I , Tada Yoshiteru ,   The Univ. of Tokushima, Wada Kosuke , Makino Hiroshi , Kudo Mari , Murakami Shoko , Turan Nefize , Nagahiro Shinji , Hashimoto Tomoki
Published: July 2021

Background and Purpose
Subarachnoid hemorrhage resulting from the rupture of intracranial aneurysms causes severe morbidity and high mortality. Statins exert anti-inflammatory and anti-oxidative effects on the vasculature independent of their cholesterol-lowering properties. The protective effects of simvastatin, a common lipophilic statin, have been examined in various diseases. However, the role of statins on the rupture of intracranial aneurysms is still controversial. We hypothesized that simvastatin can prevent intracranial aneurysmal rupture.

Methods
Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and deoxycorticosterone acetate salt hypertension. Six days after aneurysm induction, daily treatments of vehicle control (n=32), and simvastatin (30mg/kg/day; n=32) were started. Mice were sacrificed when they developed neurological symptoms, or 21 days after aneurysm induction if mice did not have symptoms. In situ zymography and dihydroethidium staining were performed to detect gelatinase activity by matrix metalloproteinases (MMPs) and superoxide production, respectively.

Results
Simvastatin decreased the incidence of ruptured aneurysms (
Figure
) compared to vehicle control mice (28% vs. 63%, P<0.05). Simvastatin also improved the survival of mice with aneurysms. Simvastatin reduced superoxide production and gelatinase activity in aneurysmal walls, indicating that simvastatin treatment was effective.

Conclusion
Simvastatin reduced the incidence of intracranial aneurysmal rupture in mice. Furthermore, simvastatin reduced superoxide production and MMP-related gelatinase activity in aneurysmal walls. Simvastatin may have potentially protective effects against intracranial aneurysmal rupture via its anti-inflammatory and anti-oxidative properties..
Abstract 2856: Lesion load of Corticospinal Tract and Initial Motor Impairment in the Acute Stroke Phase Predict Motor Impairment 3 Months Post-Stroke
Authors: Feng Wuwei , Wang Jing , Sidorov Evgeny , Holmstedt Christine , Doughty Christopher , Schlaug Gottfried
Published: July 2021

Background:
We use lesion-mapping techniques in combination with diffusion tensor imaging to quantitatively test the hypothesis that motor impairment 3 months post- stroke is inversely related to the lesion load of the corticospinal tract (CST) in the acute stroke phase.

Methods:
We prospectively followed up a cohort of 32 patients who presented with their first-ever acute ischemic stroke with various degree of motor deficit , had a MRI during the hospitalization, and had follow-up motor assessments using the Fugl-Meyer Upper Extremity Scale (FM-UE) at 3 months (+/- 2 weeks) after stroke. We calculated a CST-lesion load for each patient by overlaying the patient’s lesion map from diffusion weighted image with a probabilistic DTI tract constructed from 12 age-matched healthy subjects . Both raw and weighted (which accounts for the narrowing of the CST as it descends from the motor cortex to the posterior limb of the internal capsule) were calculated; weighted lesion-loads were calculated by multiplying the lesion-tract overlap on each slice by the ratio of the maximum cross-sectional area of the tract to the cross-sectional area of the tract on that particular slice). A multiple regression is fit to assess the predicted value of CST lesion load (raw or weighted), along with other variables such age, gender, lesion size, initial impairment, days of therapy known to have an possible effect on motor outcome.

Results:
CST-lesion load and initial motor impairment are found to be significant predictors of upper extremity motor impairment at 3 months post-stroke. Age, gender, lesion size or days of therapy does not have predictive value in our cohort study. The adjusted R² is 0.63 with initial impairment and raw lesion load in the regression model, and is 0.66 with initial impairment and weighted lesion load.

Conclusions:
Our data shows the degree of motor impairment at 3 months after a first-ever ischemic stroke can be predicted by the overlap of the lesion with the canonical CST derived from age-matched healthy control subjects and the initial motor impairment measured in the acute phase.
Abstract 2870: Influence Of The Vkorc1 And Cyp2c9 Genotypes On The Frequency Of Bleeding And Maintenance Warfarin Dose In Russian Population
Authors: Kropacheva Ekaterina
Published: July 2021

Purpose:
Warfarin (W) is a highly effective drug for prevention and treatment of arterial and venous thromboembolic disorders. Bleeding is the most important complication of the oral anticoagulation. We investigated the genetic predictors of the bleeding complications in patients on long-term adjusted-dose W therapy.

Methods:
The study included 86 pts (46 male), age 62,8±10,6(SD) years receiving long-term W therapy (international normalized ratio (INR) 2-3). The observation duration was from 1 month to 1 year.
CYP2C9
(CYP2C9*2
and
CYP2C9*3), VKORC1
G3673A genotypes were identified by the polymerize chain reaction. The indications for W therapy were: atrial fibrillation-83,7% (CHADS2 2±1,3);deep venous thrombosis-7%; LV thrombus-4,65%; prosthetic heart valve-4,65%. Arterial hypertension had 62% of pts, coronary artery disease (CAD)- 26%, congestive heart failure (NYHA II-IV)- 30%, previous ischemic stroke-12% and diabetes- 8%.

Results:
The frequency of
VKORC1
GG,
VKORC1
GA and
VKORC1
AA were 31%, 55% and 14 %, respectively. The frequency of
CYP2C9*1, CYP2C9*2
and
CYP2C9*3
were 67,8%, 15,5% and 14,3%. 2 pts (2,4%) had
CYP2C9*2/*3
genotype. The mean W daily dose was the highest in wild-type pts (
CYP2C9*1/*1
and
VKORC1 GG
genotypes together): 7±2,18 mg/day as compared with pts with only one: 5,1±1,85 mg/day (p=0,006) or combination of a
VKORC1
and a
CYP2C9
polymorphism: 3,4±1,37 mg/day (p=0,03). The carriers of the combination of
VKORC1
and
CYP2C9
polymorphism demonstrated higher frequency of the INR fluctuation (INR>3) as compared with wild-type pts: 81% vs 38% (p=0,03). Only the carriers of the combination of GA/AA and
CYP2C9*3
genotypes had higher frequency of bleedings as compared with wild-type pts: 67% vs 12,5% (p=0,03), respectively. The possession of the
VKORC1
AA and/or
CYP2C9*3
genotypes, mean INR>2,5 during observation period, female gender and CAD were predictors of bleeding events according to the multivariate discriminant analysis (p<0,00001).

Conclusions:
The carriers of the combination of
VKORC1
and
CYP2C9
polymorphism required lower maintenance W dose and demonstrated more INR fluctuations. Only the carriers of the combination of
VKORC1
GA/AA and
CYP2C9*3
genotypes demonstrated more bleedings. The possession of
VKORC1
AA and/or
CYP2C9*3
genotypes was one of the predictors of bleeding events on W therapy.
Abstract 2874: Functional Polymorphisms in Toll-like Receptor 4 Predict Worse Outcome in Acute Ischemic Stroke Patients
Authors: Weinstein Jonathan R , Schulze Juliane , Lee Richard V , Zierath Dannielle , Tanzi Patricia , Shibata Dean , Becker Kyra J
Published: July 2021

Background:
Toll-like receptor-4 (TLR4) plays a central role in the pathophysiology of acute ischemic stroke (AIS). Specific single nucleotide polymorphisms (SNPs) in TLR4 including 1063 A/G [Asp299Gly] and 1363 C/T [Thr399Ile] alter immune cell responsiveness to lipopolysaccharide (LPS) and are associated with increased rates of infection. The effect of these TLR4 SNPs on outcome following AIS is unknown.

Methods:
Patients were prospectively enrolled after onset of AIS. Clinical and demographic data were collected and neurological outcomes assessed at 3 months. Blood was drawn at multiple time points to quantify leukocyte subsets and assess plasma levels of C-reactive protein and a panel of cytokines. Genotyping for the TLR4 SNPs was also performed on blood samples. Uni- and multivariate analyses were performed to assess associations between TLR4 SNP haplotype and (i) each laboratory parameter noted above, (ii) infection risk and (iii) stroke outcome.

Results:
Of the 42 patients included; 6 (14%) were heterozygous for either one or both TLR4 SNPs. Baseline characteristics were similar in patients with or without a TLR4 SNP. In analyses adjusted for both initial stroke severity and age, the presence of a TLR4 SNP was associated with increases in blood leukocytes, plasma C-reactive protein and the cytokine interleukin-1 receptor antagonist (IL-1ra). The presence of either TLR4 SNP was also associated with a trend toward increased rates of infection (adjusted odds ratio and 95% confidence interval of 8.20 and 0.826-81.5, respectively) and a decreased likelihood of favorable outcome as defined by a modified Rankin Scale score of two or less at three months from stroke onset (0.014, 0.00-0.759).

Conclusions:
In AIS patients, functionally significant genetic variations in TLR4 influence both rates of stroke-associated infection and neurological outcome. These data suggest a direct connection between TLR4 function and stroke pathophysiology.
Abstract 2917: Outcome Prediction With A Population-based Ischemic Stroke Atlas
Authors: Nowinski Wieslaw L , Gupta Varsha , Qian Guoyu , Ambrosius Wojciech , He Jie , Kazmierski Radosław
Published: July 2021

Outcome prediction is critical in stroke patient management. We propose a novel approach combining imaging with parameters (including history, hospitalization, demographics, clinical and outcome) for a population of patients in the Probabilistic Stroke Atlas (PSA) along with prediction engine. The PSA aggregates multiplicity of data for a population of stroke patients and presents them in image format. The PSA is composed from a series of three-dimensional (3D) image volumes including scans and parameters. A cohort of over 700 ischemic stroke generally treated patients with 176 parameters per patient, and CT scan performed at admission and on day 7 was acquired. Outcome measurements were assessed up to one year after stroke onset. Cases with old infarcts, infarcts in both hemispheres, and hemorrhagic transformations were rejected. This data was post-processed to build the PSA and then the PSA was used for prediction. The infarcts were delineated on CT scans and their 3D surface models constructed and normalized. The PSA was calculated from the normalized 3D infarct models as frequency of stroke occurrence. Similar maps were calculated for the following parameters: Age; Sex; Survival; NIH Stroke Scale (NIHSS); Barthel Index (BI) at 30, 90, 180, 360 days; modified Rankin Scale (mRS) at 7, 30, 90, 180, 360 days; White blood cell count; C-reative protein; Glucose at emergency department; History of hypertension; and History of diabetes. The PSA was used for prediction of mRS and BI for 50 stroke subjects. For a given case to be predicted, the infarct was delineated and analyzed by the PSA mapped on the scan. The predicted values of the parameters from the PSA were compared with the actual values of the parameters measured in up to 1-year neurological follow up. The accuracy was defined as 100*(1-(actual value-predicted value)/actual value)%. The mean prediction accuracy of mRS at (7, 30, 90, 180, 360) days is (89.7, 90.7, 92.1, 87.0, 83.3)% and that for BI at (30, 90, 180, 360) days is (90.0, 95.4, 94.4, 92.2)% respectively. This novel prediction method has high prediction rates. It can be applied to any other parameters. The PSA is dynamic and its power can increase with additional cases.
Abstract 2954: Evaluating the Retention of Stroke Education Provided to the Hospitalized Patient with Acute Ischemic Stroke in an Urban Hospital
Authors: Schnepel Loretta , Shockley Stubits Debra , Johnson Yvonne , Miller Terri , Hodges Wayne , Brock Falk Diane , Lukens Bull Katryne , Smotherman Carmen , Sanders Kalina , Silliman Scott
Published: July 2021

Background and Purpose:
The Joint Commission mandates that certified Primary Stroke Centers provide patient education addressing stroke warning signs, use of 911 for access to emergent care, personal risk factors, medications prescribed, and follow-up after discharge. The patient’s retention of this information is imperative for reducing secondary stroke occurrence and morbidity. This study evaluated the Acute Ischemic Stroke (AIS) patient’s ability to retain the stroke education information provided near the time of hospital discharge.

Methods:
A prospective hospital-based cohort study was comprised of AIS patients who were admitted to the stroke unit at an urban core hospital located in Jacksonville, Florida. Diagnosis of AIS was confirmed by a Neurologist and by a CT or MRI. All participants received Joint Commission mandated stroke education administered by a nurse during their hospitalization. The patient education included verbal instructions with the use of illustrative handouts. Stroke education retention was evaluated near the time of hospital discharge using a five-question survey. The level of health literacy was assessed by the Short Version-Test of Functional Health Literacy in Adults (S-TOFLHA).

Results:
Of 189 consecutive patients screened between October 2009 and June 2010, 100 (53%) consented to participate. Seventy patients were excluded due to severe cognitive impairment, and 18 eligible patients refused to participate. The average age was 60 years old, 57% were male, 56% African American, 43% resided within the urban core, and 75% earned less than $25,000 per year. A total of 59% of patients had low to marginal health literacy. Retention of stroke knowledge was lacking even with standard stroke post education; 12% could name all 5 warning signs, 43% knew their personal risk factors, 85% knew to call 911 for warning signs of stroke, 76% knew their medications prescribed for stroke prevention, and 53% knew their type of stroke.

Conclusion:
Current methods of educating hospitalized AIS patients may not adequately prepare the hospitalized stroke survivor with basic knowledge on stroke prevention. Alternative methods of education will need to be developed for AIS patients in urban core hospitals. By using the Patient-Centered Care model and principles of adult learning, this study has the potential to lead to changes in educational interventions, nursing practices, and communication.
Abstract 2961: Basilar Artery Diameter Is Associated With The Severity Of Cerebral Small-vessel Disease In Patients With Vascular Risk Factors
Authors: Tanaka Makiko , Miwa Kaori , Okazaki Shuhei , Furukado Shigetaka , Sakaguchi Manabu , Kitagawa Kazuo
Published: July 2021

Background and purpose:
Basilar arterial dolichoectasia (extreme enlargement and elongation) has been reported to be associated with cerebral small-vessel disease (CSVD) in stroke patients. The association of moderate dilatation of the basilar artery (BA) and CSVD or cerebrovascular risk factors is not clear. We analyzed BA diameter, stroke and white matter lesions, and other clinical factors in patients with atherosclerotic risk factors.

Methods:
The study subjects were 411 outpatients aged 50 or over who underwent brain magnetic resonance imaging (MRI) for clinical purposes. All patients had 1 or more atherosclerotic risk factors. The minor axis of the BA diameter was measured on the axial view of the T2-weighted MRI at midpons level. The location and size of the symptomatic and asymptomatic stroke lesions were evaluated. The severity of the deep white matter lesions were also assessed with Schelten’s score system by MRI. The anatomic variation in the posterior circle of Willis was assessed by MR angiography.

Results:
The diameter of BA was < 2.0 mm in 71 patients, 2.0 - 2.9 mm in 212 patients, 3.0 - 3.9 mm in 115 patients, 4.0 - 4.5 mm in 11 patients, and > 4.5 mm in 2 patients. In the univariate analysis, age, male gender, hypertension, low HDL cholesterol, the history of ischemic heart diseases, the presence of stroke lesions, and severity of deep white matter lesions were associated with BA diameter. Patients with infarctions ≤ 15 mm had larger size of BA than those with infarctions > 15 mm and those without infarctions. Patients with a bilateral adult-type posterior cerebral artery (PCA) had larger BA diameter than those with other types of PCA. In the multivariate regression analysis, male gender (P = 0.0002), the presence of stroke lesions (P = 0.009), severity of deep white matter lesions (P < 0.0001), and the variation in the posterior circle of Willis (P < 0.0001) were independently associated with BA diameter.

Conclusion:
BA diameter is associated with the severity of CSVD in high-risk patients. Dilatation process of BA and the development of CSVD may have common causes.
Abstract 3066: Implementation of Results from Major Clinical Trials on Utilization Patterns of Antithrombotic Agents following Noncardioembolic Ischemic Stroke or TIA in the United States (2000-2009)
Authors: Khan Amir , Chaudhry Saqib A , Suri M. Fareed K , Qureshi Adnan I
Published: July 2021

Background and Purpose:
Several large trials published over the last decade have significantly altered recommended guidelines for therapy following a noncardioembolic ischemic stroke or transient ischemic attack (TIA). We examined utilization patterns of these agents over the last decade, with regards to the publication of the MATCH, ESPRIT, and PRoFESS clinical trials, to study the implementation of the results of such trials in clinical practice.

Methods:
Antithrombotic utilization was prospectively collected as part of the National Ambulatory Medical Care Survey (NAMCS) between 2000 and 2009. Patients with a history of ischemic stroke or TIA were included with the exception of those with a concomitant history of atrial fibrillation, atrial flutter, or heart valve replacement. Annual utilization prevalence of the following antithrombotic strategies was compared: aspirin monotherapy, clopidogrel monotherapy, combined clopidogrel and aspirin, dipyridamole-aspirin, and warfarin. Average annual prevalence was compared before and after publication of MATCH in 2004, ESPRIT in 2006, and PRoFESS in 2008. A second pre-specified analysis excluded patients with known coronary artery disease (CAD) to censor the use of combined clopidogrel and aspirin for treatment of CAD after the 2001 CURE and 2002 CREDO trials showed a benefit of extended dual antiplatelet therapy.

Results:
An annual average of 4,221,059 patients between 2000 and 2009 met criteria for evaluation. After the 2004 MATCH trial, the annualized rate of combined clopidogrel and aspirin use increased from 3.3% before trial publication to 6.8% afterwards (p<0.0001). When patients with CAD were excluded an increase of 3.3% to 5.5% was found during the same period (p<0.0001). Following the 2006 ESPRIT trial, the annualized rate of dipyridamole-aspirin use increased from 2.8% to 4.6% (p<0.0001); the annualized rate of clopidogrel use increased from 12.8% to 17.8% (p<0.0001); and the annualized rate of aspirin use increased from 12.6% to 16% (p<0.0001). After the PRoFESS trial, published in late 2008, the annualized rate of clopidogrel use increased from 13.8% to 19% (p<0.0001); the annualized rate of dipyridamole-aspirin use minimally increased from 3.3% to 4% (p<0.0001); and the annualized rate of aspirin use decreased from 14.2% to 11% (p<0.0001).

Conclusion:
The impact of the MATCH, ESPRIT, and PRoFESS trials on antithrombotic utilization has been variable. The results highlight the importance of addressing factors that facilitate or hinder the implementation of results from such trials into practice.
Abstract 3070: Assessment of Manual Aspiration Therapy for the Treatment of Sinus Thrombosis
Authors: Bodily Lance , Jumaa Mouhammad , Zaidi Syed , Jovin Tudor , Jankowitz Brian
Published: July 2021

Objective:
While hydration and anticoagulation is typically the standard of care for cerebral venous sinus thrombosis, some patients remain refractory to medical management and continue to deteriorate. In these instances a number of more aggressive endovascular techniques have been reported to remove clots and restore blood flow in the venous sinuses. These techniques include direct thrombolysis, angioplasty, and various methods to disrupt and aspirate clot. Here we present the technique of endovascular transvenous manual aspiration thrombectomy (MAT) in five patients.

Methods:
We reviewed the records of five patients with medically refractory cerebral venous sinus thrombosis who received transvenous MAT. Presentation, technique, and outcome were evaluated.

Results:
Out of the five cases reviewed presentation included vomiting, dehydration, mental status changes, headaches, and acute motor deficits. On imaging three of the five patients had hemorrhage, edema, and mass effect present before treatment, while two had edema only. All of the patients reviewed were treated with anticoagulation therapy, intravenous heparin or subcutaneous lovenox, for a minimum of 24 hours. However, all of the patients continued to deteriorate despite early and aggressive medical anticoagulation therapy. All of the patients demonstrated rapid and progressive worsening of their neurological exam pre-operatively, including lack of arousal, pathological posturing, and expansion of secondary hemorrhages. This rapid deterioration warranted aggressive intervention, making the patients candidates for endovascular therapy. Direct thrombolysis with tPA was utilized with MAT via a distal access catheter(DAC) in all but one patient in which tPA was not used due to concern for hemorrhage. Aspiration of the superior sagittal sinus, transverse sinuses, straight sinus, and internal jugular were all included in this series. Catheters included the 0.070, 0.057, and 0.044 DAC and the 0.054 Penumbra microcatheter. Revascularization was achieved in all instances. One patient presented and remained neurologically devastated. She died 5 days after treatment. All other patients experienced improvement in their neurological examinations and were eventually discharged from the hospital in stable condition.

Conclusions:
Endovascular transvenous MAT is a feasible and effective revascularization technique to treat patients with cerebral venous sinus thrombosis.
Abstract 3086: Safety of Induced Hypertension in Acute Ischemic Stroke Patients with Suboptimal Recanalization after Endovascular Thrombolysis.
Authors: Cordina Steve M , Majidi Shahram , Chaudhry Saqib A , Hassan Ameer E , Rodriguez Gustavo J , Suri M. Fareed K , Qureshi Adnan I
Published: July 2021

Background:
Induced hypertension is feasible, likely safe and can improve neurologic deficits in patients who are not candidates for thrombolysis. The safety of inducing hypertension in post-thrombolytic patients with suboptimal recanalization after endovascular thrombolysis is not currently known.

Objective:
To determine the feasibility and safety of inducing hypertension in patients in the acute post thrombolytic phase.

Methods:
We analyzed retrospectively collected data from a database of patients who presented with acute ischemic stroke and who received endovascular treatment with or without intravenous (IV) r-tPA . Patients with suboptimal recanalization after endovascular thrombolysis underwent induction of hypertension (systolic blood pressure [SBP] target 140-180 mmHg) for a 24 hour period after an immediate post-procedure CT scan did not demonstrate any intracerebral hemorrhage (ICH). We determined the rate of symptomatic ICH (sICH), and outcome based on modified Rankin score (mRS) at the time of discharge and compared these data to those observed in patients with non-induced hypertension and normotension. Multivariate logistic regression analysis was used to identify the odds ratio of neurological worsening and/or death after adjusting for initial National Institute of Health Stroke Scale (NIHSS) score and success of hypertension induction, which was defined as a sustained mean BP of ≥ 30% above the admission BP over the first 24 hours.

Results:
A total of 16 patients (12%, mean age 66) underwent post-thrombolytic induced hypertension among 138 patients who were treated with endovascular treatment. The mean age (± standard deviation [SD]) of treated patients was 68 (± 15.3) years and 52 (46%) were women. Hypertension was induced using intravenous phenylephrine or norepinephrine infusion in 9 and 7 patients, respectively. The mean (±SD) increase in SBP was 140 (±16.4) mmHg. In multivariate analysis, patients with post-thrombolytic induced hypertension had similar risk of sICH (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.11-8.55) and similar discharge mRS (OR 1.85, 95% CI 0.50-6.84).

Conclusion:
There was no observed increase in sICH or poor outcomes associated with induced hypertension in patients with suboptimal recanalization after endovascular thrombolysis supporting safety. Further trials directed towards assessing efficacy of this approach are needed.
Abstract 3106: Vascular Cognitive Impairment (VCI) Risk Factors Produce Deficits in Cognition and Gait-Balance with Fiber Tract Pathology and Inflammation in a Rat Model of VCI
Authors: Barone Frank , Li Jie , Baird Alison , Adamski Mateusz , Dow-Edwards Diana , Bergold Peter , Abdel baki Samah , Crystal Howard , Rosenbaum Daniel , Zhou Jin
Published: July 2021

Background:
Cerebrovascular risk factors are important to model VCI. VCI symptoms include cognitive deficits in executive function and gait associated with reduced forebrain perfusion and fiber tract injury. Ischemia mobilizes progenitor CD34+ cells from bone marrow. Here important risk factors are incorporated into a translational VCI model.

Methods:
Clinic:
The relationship between blood pressure and carotid lesions on cognitive outcome were assessed in linear regression models.
Preclinic
: Bilateral common carotid artery
Stenosis
surgery (guided by reduced forebrain perfusion) or
Sham
surgery was performed in spontaneously hypertensive rats (SHR). Measurements of neurological (gait-balance, sensory-motor and activity) and cognitive (avoidance tests: active place; APA and passive; PA) functions were made. Quantitative histological measurements were made of CA1 neurons (NeuN) and corpus collosum (CC) myelin (Luxol Fast Blue) and astro- (GFAP) and micro- (Iba1) gliosis. Circulating CD34+ progenitor cells were measured using a fluorescence-activated cell analyzer.

Results:
Clinic:
Carotid lesions (p < 0.01) and hypertension (p< 0.05) were independent predictors of cognitive impairment.
Preclinic
:
Stenosis
decreased forebrain perfusion and impaired APA and gait-balance within 3 weeks (p<0.01). Motor activity, blood pressure, heart rate, body weight and simple PA performance were not affected. CC myelin was reduced (48%; p<0.01) with increased astro- (69%; p<0.05) and micro- (140%; p<0.01) gliosis. CA1 neurons were not changed. Circulating CD34+ progenitor cells were significantly increased (p< 0.02).

Conclusions:
Clinic:
Carotid stenosis and hypertension are associated with cognitive impairment.
Preclinic
: Carotid stenosis in the hypertensive rat results in cognitive and gait-balance deficits that mimic VCI. APA mimics “executive function-like” decision making and is a sensitive indicator of preclinical VCI. Deficits are associated with CC injury and inflammation-gliosis but not CA1 cell loss. Increased progenitor cells suggest a potential for carotid reperfusion, cellular and/or growth factor restorative therapy. This VCI model provides an important tool to probe white matter injury, mechanisms and interventions in VCI.
Abstract 3138: Hospitalization Costs for Acute Ischemic Stroke Patients Treated with Endovascular Embolectomy in the United States
Authors: Brinjikji Waleed , Kallmes David F , Lanzino Giuseppe , Rabinstein Alejandro A , Cloft Harry J
Published: July 2021

Background and Purpose-
It is important to know the costs for hospitalization for endovascular embolectomy patients so that comparisons can be made to payments to hospitals.

Methods-
Using the National Inpatient Sample, we evaluated the costs for hospitalization for patients treated with endovascular embolectomy in the United States from 2006-2008. The primary endpoint examined in this study was total hospital costs, and these were correlated with clinical outcome. Hospitalization costs were then compared with Medicare payments for their respective outcomes. MS-DRG 24 was the diagnostic related group code (DRG) for mechanical embolectomy with good outcome and MS-DRG 23 was the DRG code for mechanical embolectomy with major complications. Medicare payments were available at
http://www.cms.hhs.gov
.

Results-
A total of 3864 patients received endovascular embolectomy. 1649 patients were <65 years old and 2205 patients were ≥65 years old. Median hospital costs in 2008 dollars were $36,999 (IQR $26,662-$56,405) for patients with good outcome, $50,628 (IQR $33,135-$76,063) for patients with severe disability, and $35,109 (IQR $25,053-$62,621) for patients with mortality. Reimbursement in the year 2008 for DRG 24 (good outcome) was $22075 and reimbursement for DRG 23 (major complications) was $26639.

Conclusions-
Our study of the NIS shows that hospitalization costs in the United States for ischemic stroke patients treated with endovascular embolectomy are rather high, probably due to the serious nature of their illness. Medicare payments have not been adequate in reimbursing these hospitalizations. Further work is needed to ensure the future reconciliation of costs with payments.
Abstract 3139: The microRNA 17-92 Cluster Mediates Sonic Hedgehog-driven Neurogenesis In Ischemic Neural Progenitor Cells
Authors: Liu Xianshuang , Chopp Michael , Tang Tao , Kassis Haifa , Xu Jennifer , Hozeska-Solgot Ann , Zhang Li , Zhang Rui Lan , Zhang Zheng Gang
Published: July 2021

Background:
The Sonic hedgehog (Shh) pathway regulates stroke-induced neurogenesis. The present study investigated the functional role of the microRNA 17-92 (miR17-92) cluster in this process.

Methods and Results:
Analysis of miRNA microarray and real-time RT-PCR revealed that stroke substantially increased levels of individual members of the miR17-92 cluster: miR-18a (1.8±0.3), miR-19a (2.5±0.4), and miR-92a (1.9±0.3) expression in neural progenitor cells (NPCs) harvested from the subventricular zone (SVZ) of ischemic rats (n=6). Overexpression of the miR17-92 cluster in cultured NPCs significantly increased NPC proliferation measured by the number of BrdU positive cells (52±4% vs 28±2% in empty vector, n=3/group, p<0.05). Concurrently, overexpression of the miR17-92 cluster reduced PTEN (phosphatase and tensin homolog), a target of the miR17-92 cluster, protein levels by 70% compared to levels in NPCs transfected with an empty vector. PTEN suppresses cell proliferation. These data suggest that the stroke-upregulated miR17-92 cluster enhances NPC proliferation via downregulation of PTEN. To examine whether Shh regulates miR17-92 cluster expression, NPCs were incubated with recombinant human Shh (rhShh, 100ng/ml). We found that rhShh significantly (p<0.05) increased levels of individual members of the miR17-92 cluster: miR-18a (2.1±0.1), miR-19a (1.3±0.7), miR-19b (1.5±0.6) and miR-92a (1.9±0.8). Blockage of a Shh receptor Smo with cyclopamine suppressed rhShh-increased levels of miR-18a (0.9±0.08), miR-19a (0.7±0.01), miR-19b (0.6±0.05) and miR-92a (0.8±0.04). Attenuation of endogenous Shh in NPCs with siRNA also substantially decreased levels of miR-18a (0.6±0.1), miR-19a (0.4±0.05) and miR-92a (0.6±0.1) compared with levels in NPCs transfected with scrambled siRNA (1.0±0.2, n=3), indicating that Shh regulates miR17-92 expression. MYC is a downstream target of Shh. Western blots showed that stroke increased the protein level of N-MYC 1.8 fold in SVZ tissues and incubation of NPCs with rhShh elevated N-MYC levels by 1.8 fold, which was abrogated by cyclopamine (1.3 fold). N-MYC transduction resulted in significant increases in expression of the primary miR17-92 cluster (2.1±0.3 vs 1.0±0.2 in control group, n=3, p<0.05). These data suggest that the Shh pathway recruits N-MYC to regulate miR17-92 cluster expression in NPCs.

Conclusion:
Our data suggest a functional role of the miR17-92 cluster in mediating stroke-induced neurogenesis by the SHH/MYC signaling pathway, which provides new insight into molecular mechanisms of stroke-induced neurogenesis.
Abstract 3200: Comparison of CT Perfusion Mismatch with Perfusion-Diffusion MRI in Ischemic Stroke - a Reliable Alternative?
Authors: Campbell Bruce C , Christensen Søren , Levi Christopher R , Desmond Patricia M , Donnan Geoffrey A , Davis Stephen M , Parsons Mark W
Published: July 2021

Background and purpose:
CT-perfusion (CTP) is widely and rapidly accessible for imaging acute ischemic stroke. However, there has been limited validation of CTP parameters against the more intensively studied MRI perfusion-diffusion mismatch paradigm. We tested the correspondence of CTP with contemporaneous perfusion-diffusion MRI.

Methods:
Acute ischemic stroke patients <6hr after onset had CTP and perfusion-diffusion MRI within 1hr, before reperfusion therapies. Relative cerebral blood flow (relCBF) and time-to-peak of the deconvolved tissue-residue-function (Tmax) were calculated (standard singular value decomposition deconvolution). The diffusion lesion was registered to the CTP slabs and manually outlined to its maximal visual extent. CT-infarct core was defined as relCBF<31% contralateral mean as previously published using this software. The volumetric accuracy of relCBF core compared to the diffusion lesion was tested in isolation, but also when restricted to pixels with relative time-to-peak (TTP) >4sec, to reduce artifactual false positive low CBF (eg in leukoaraiosis). The MR Tmax>6sec perfusion lesion (previously validated to define penumbral tissue at risk of infarction) was automatically segmented and registered to the CTP slabs. Receiver operating characteristic (ROC) analysis determined the optimal CT-Tmax threshold to match MR-Tmax>6sec, confidence intervals generated by bootstrapping. Agreement of these CT parameters with MR perfusion-diffusion mismatch on co-registered slabs was assessed (mismatch ratio >1.2, absolute mismatch>10mL, infarct core<70mL).

Results:
In analysis of 98 CTP slabs (54 patients, median onset to CT 190min, median CT to MR 30min), volumetric agreement with the diffusion lesion was substantially improved by constraining relCBF<31% within the automated TTP perfusion lesion ROI (median magnitude of volume difference 9.0mL vs unconstrained 13.9mL, p<0.001). ROC analysis demonstrated the best CT-Tmax threshold to match MR-Tmax>6sec was 6.2sec (95% confidence interval 5.6-7.3sec, ie not significantly different to 6sec), sensitivity 91%, specificity 70%, AUC 0.87. Using CT-Tmax>6s “penumbra” and relCBF<31% (restricted to TTP>4s) “core”, volumetric agreement was sufficient for 90% concordance between CT and MRI-based mismatch status (kappa 0.80).

Conclusions:
Automated CTP mismatch classification using relCBF and Tmax is similar to perfusion-diffusion MRI. CTP may allow more widespread application of the “mismatch” paradigm in clinical practice and trials.
Abstract 3206: Obesity Paradox in Acute Ischemic Stroke: Analysis of 34,132 Patients from Korean Stroke Registry
Authors: Kim Beom Joon , Lee Seung-Hoon , Jung Keun-Hwa , Yu Kyung-Ho , Lee Byung-Chul , Roh Jae-Kyu ,   Korean Stroke Registry investigators
Published: July 2021

Background.
Paradoxical longevity in obese patients with established disease has been reported in various conditions. However, detailed investigations involving acute ischemic stroke patients are scarce. We aimed to detect obesity paradox in acute ischemic stroke patients with stratified analyses based on age and causes of mortality.

Methods.
Korean Stroke Registry (KSR) is a nationwide, multicenter and prospective registry of acute stroke. During 7.5 years, 34 132 acute ischemic stroke patients were collected through 30 participating centers. The mortality information was ascertained through a governmental statistical office, as current of December 2009. Multiple imputation by IVEware was used to estimate missing data on the basis of observed information and to account for potential variance due to uncertainty of missingness.

Results.
Among a total of 34,132 acute ischemic stroke patients analyzed in this study, 1,348 patients (4.7%) were classified as underweighted (BMI <18.5), 10,888 (37.7%) as normal weight (18.5 - 22.9), 7,666 (26.5%) as overweight (23 - 24.9), 8,056 (27.9%) as obesity I (25.0 - 29.9), and 924 (3.2%) as obesity II (≥30; BMI missing in 5,250 patients), at the time of admission. During mean follow-up of 32.6 ± 23.1 months, 9,073 patients (26.6%) were deceased up to June 2009. Mortality rates of the included patients at various time-points were as followed; 4.1% (1,410 subjects) at 1-month, 7.0% (2,394) at 3-month, and 13.0% (4,373) at 1-year after stroke. Compared with body mass index (BMI) value of 20 - 23, stroke survivors with lower BMI values had increased risk of mortality (HR 1.36, 95% CI 1.25 - 1.48 for BMI ≤18.5; HR 1.14, 95% CI 1.03 - 1.26 for BMI 18.5 - 20). Likewise, obese stroke patients had decreased risk of mortality (HR 0.83, 95% CI 0.74 - 0.92 for BMI 27.5 - 30; HR 0.77, 95% CI 0.63 - 0.93 for BMI 30 - 32.5; see
Figure
). Inverse association between obesity status and mortality was not evident until 90 days after stroke, but became significant 1 year after onset of stroke. The association between obesity status and mortality was stronger in young-age group than in old-age group, but significance was maintained through all age-strata. The obesity paradox remained significant regardless of mortality causes, such as cancer death, vascular death and other causes of death.

Conclusion.
From our study, an inverse association between obesity status and long-term mortality in stroke survivors was documented, and such association was evident regardless of age or causes of death.
Abstract 3309: Enrolling the Oldest Old is Achievable in Acute Stroke Clinical Trials
Authors: Sanossian Nerses , Starkman Sidney , Liebeskind David S , Kim-Tenser May A , Restrepo Lucas , Ali Latisha K , Valdes-Sueiras Miguel , Conwit Robin , Hamilton Scott , Saver Jeffrey L ,   FAST-MAG Investigators and Coordinators
Published: July 2021

Background:
Acute stroke clinical trials have frequently excluded the very elderly, leading to a lack of data regarding therapy effect in this rapidly growing population. We sought to describe the frequency and characteristics of the oldest old (patients aged 80-95) enrolled in an ongoing multicenter prehospital treatment trial, the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study.

Methods:
FAST-MAG is a phase 3, NIH-funded, randomized, double-blind study of field-administered magnesium sulfate vs. placebo in stroke patients enrolled within 2 hours of symptom onset. All patients who were not disabled prestroke up to age 95 are eligible for enrollment.

Results:
Among the first 1207 subjects enrolled in FAST-MAG, 353 (29%) were >= 80 and 42 (4%) were >= 90 years old. Compared with younger trial subjects, individuals >=80 years old had higher mean age (85 v 63, p<0.0001), were more often women (53% vs. 38%, P<0.0001), less often Hispanic ethnicity (13% v 27%, p<0.0001), more often racially white (87% v 76%, p<0.0001), and were less likely to have intracerebral hemorrhage (15% v 28%, p<0.0001). However, the very elderly had similar stroke deficit severity (NIHSS 11 v 11, p=0.65) and were evaluated by paramedics (mean 37 v 37 min) and arrived in the ED (73 v 71 min, p=0.65) at similar time points. In the field, the very elderly had similar SBP (160 v 158, p=0.59) but lower DBP (78 v 86, p<0.0001). Medical history variables distinguishing the very elderly from younger patients were higher frequency of HTN (87% vs. 77%, P<0.0001), atrial fibrillation (40% vs. 17%, p<0.0001), coronary artery disease (27% vs 18%, p<0.0001), and lower tobacco use (4% vs 23%, p<0.0001). Rates of TPA use among cerebral ischemia patients did not differ between the very elderly and younger patients (31% v 28%, p=0.507). The subgroup of extremely old patients, aged 90-95, were similar to patients aged 80-89, except there were no smokers, and even higher proportions were women (69%), non-Hispanic (91%) and white (93%).

Conclusions:
The very elderly can account for nearly 3 in 10 patients enrolled in a hyperacute stroke treatment trial. The oldest old have distinct clinical characteristics, indicating that their inclusion is in clinical trials is important for study results to be widely generalizable to clinical practice.
Abstract 3346: Design of Multi-center, Randomized, Open-label, Blind-endpoint Trial Comparing Effects of Cilostazol versus Other Anti-platelet Drugs for the In-stent Restenosis after Carotid Artery Stenting : The Carotid Artery Stenting with Cilostazol Addition for Restenosis (CAS-CARE) Trial
Authors: Yamagami Hiroshi , Sakai Nobuyuki , Ogasawara Kuniaki , Nagata Izumi , Matsumaru Yuji , Yoshimura Shinichi , Sasaki Makoto , Nagatsuka Kazuyuki , Minematsu Kazuo ,   CAS-CARE Investigators
Published: July 2021

Background and Purpose:
Carotid artery stenting (CAS) is increasingly used to treat high-grade carotid stenosis, but the impact of medication on carotid in-stent restenosis (ISR) has not been shown. The present study was conducted to evaluate the inhibitory effect of cilostazol on ISR, compared to that of other antiplatelet drugs, in patients scheduled to undergo CAS.

Methods:
The Carotid Artery Stenting with Cilostazol Addition for Restenosis (CAS-CARE) trial is a multi-center, prospective, randomized, open-label, blind-endpoint trial, designed to compare the efficacy of cilostazol versus other anti-platelet therapy on ISR after CAS. Main inclusion criteria are patients with diagnosis of carotid artery stenosis, scheduled for carotid artery stenting within 30 days of enrolment, and aged at 45 - 80 years at time of consent. Patients who suffered an ischemic stroke within 48 hours prior to enrolment or those with aortic arch syndrome, vasculitis, or collagen disease will be excluded from the study. Diagnosis of carotid artery stenosis is based on angiography (NASCET stenosis ratio > 50% for symptomatic lesion or > 80% for asymptomatic lesion), or carotid ultrasound (peak systolic velocity > 130cm/sec for symptomatic lesion or > 230cm/sec for asymptomatic lesion). Nine hundred patients will be randomized into 2 groups: the first group will receive cilostazol from at least 3 days before CAS and continue for 2 years. The second group will never receive cilostazol during the same period. Use of other antiplatelet agents and concomitant drugs is unrestricted in each group. The allocation adjusting factors are presence or absence of symptoms, presence or absence of diabetes mellitus, type of stent scheduled to be used (open cell vs. closed cell), and test center. Follow-up carotid ultrasound will be examined at 6, 12 and 24 months after CAS, and carotid restenosis ≥50% is diagnosed using velocity criteria. The primary outcome is occurrence of in-stent restenosis within 2 years after CAS and time to occurrence. Secondary outcomes include 1) occurrence of in-stent restenosis, new out-stent stenosis, or re-treatment, 2) occurrence of cardiovascular event or death from any cause, 3) occurrence of a hemorrhagic event, and 4) a composite endpoint of them.

Conclusion:
CAS-CARE will determine whether cilostazol can prevent restenosis after carotid artery stenting with an acceptable risk profile.
Abstract 3402: Use of Near-Infrared Spectroscopy during Breath Holding Test in Patients with Carotid Stenosis
Authors: Avelar Wagner M , Alessandro Carlos A , Lima Fabricio O , Li Li M , Hererra Cynthia C , Mesquita Rickson C , Covolan Roberto J , Cendes Fernando
Published: July 2021

Background:
Breath-holding index (BHI) defined with transcranial doppler (TCD) is a risk marker for stroke in asymptomatic carotid stenosis. Near-infrared spectroscopy (NIRS) is a non-invasive method that can measure changes in cerebral microvasculature hemodynamics with the use of different light wavelengths. In the present study, we correlated the cerebral hemodynamic response using NIRS to BHI in patients with carotid stenosis.

Methods:
We studied 15 patients (9 men) with the mean age of 66 years (range, 55 - 75 years). Carotid stenosis was defined by carotid duplex (1 with 50-70%, 10 with 70-99% and 4 with occlusion). Patients were instructed to hold their breath for 30 seconds after a normal inspiration for dynamic acquisition. Changes in oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR) and total hemoglobin (HbT) concentrations on the temporoparietal regions corresponding to the territory of the middle cerebral artery of both hemispheres were recorded using NIRS (28 channels, CW6, TechEn Inc. Milford, MA). BHI was calculated in a separate session with the same procedure. We correlated changes in NIRS defined parameters to BHI using the Spearman’s correlation test.

Results:
The NIRS parameters HbO, HbR and HbT showed a bimodal distribution (
fig. 1
). There was a weak correlation between BHI and HbO, HbR and HbT (r = 0.16, 0.17, 0.19, respectively) with all the subjects. When the population heterogeneity was separated, there was a strong correlation between BHI and HbR (r = 0.87) and a moderate correlation with HbO and HbT (r = 0.77 and 0.73, respectively) in the patients with carotid occlusion.

Conclusion:
NIRS was capable of identifying robust hemodynamic changes due to breath holding test. The relationship between microvascular oxygenation from NIRS and macrovascular flow from BHI was found to be quite low, potentially due to the heterogeneity of the population studied. Our results suggest that NIRS could potentially be used as a useful tool to assess the physiological state of patients with carotid stenosis.
Abstract 3438: Intracranial Arterial Occlusion and Extent of Hypoattenuation on CT Angiography Source Images may Modify the Benefit of Thrombolysis
Authors: Dzialowski Imanuel , Puetz Volker , Renger Jasmin , Khomenko Andrei , Bodechtel Ulf , von Kummer Ruediger
Published: July 2021

Background:
CT angiography source images (CTASI) improve diagnostic accuracy for ischemic brain infarction compared to non-contrast CT (NCCT). We studied whether CTASI alone or combined with the CTA occlusion status may improve patient selection for thrombolysis in an extended time window.

Methods:
We prospectively observed patients presenting with anterior circulation ischemic stroke within 12 hours from symptom onset and an NIHSS score ≥ 3. All patients underwent cranial NCCT and CTA. Patients were treated with intravenous and/or intra-arterial thrombolysis at the discretion of the treating stroke neurologist and neuroloradiologist. We determined intracranial occlusion status and applied the Alberta Stroke Program Early CT Score (ASPECTS) to CTASI. Primary clinical outcome measure was independent outcome at 3 months, defined as mRS scores 0-2. We calculated unadjusted risk ratios to assess the effect of thrombolysis on functional outcome in patients with: 1) minor ischemic changes on CTASI (CTASI-ASPECTS >5) and 2) patients with minor ischemic changes on CTASI and middle cerebral artery (MCA) occlusion.

Results:
We enrolled 102 patients with a mean age of 71 +/- 12 years, median onset-to-CTA time of 112,5 (range 37-898) min, a median NIHSS score of 9.5 (3-39), and a median CTASI-ASPECTS of 8. Sixty-two patients (61%) received any thrombolysis (56 IV, 5 IV/IA, 1 IA). MCA occlusion was present in 57 patients (56%), 80/101 (80%) assessable patients had a CTASI-ASPECTS >5 and 37/101 (37%) patients had a CTASI-ASPECTS >5 in the presence of a MCA occlusion. At 3 months, 52 (51%) patients had an independent functional outcome. When patients with CTA-SI ASPECTS > 5 received thrombolysis, 30/46 (65%) achieved an independent functional outcome, whereas 20/35 (57%) without thrombolysis were functionally independent (RR 1.1, CI 95 0.8-1.6). In patients with CTASI-ASPECTS > 5 and additional MCA-occlusion, 13/24 (54%) with thrombolysis and 3/13 (23%) without thrombolysis achieved an independent functional outcome (RR 2.3, CI 95 0.8-6.8).

Conclusion:
In our non-randomized study, the extent of CTASI hypoattenuation alone did not identify patients benefiting from thrombolysis. In the presence of an MCA-occlusion, however, CTASI might identify patients with benefit from thrombolysis in an extended time window.