bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 107: Mitochondrial Depolarization without Reactive Oxygen Species Production leads to Augmented Cerebral Vascular Relaxation via Diverse Calcium-related events in Smooth Muscle and Endothelium
Authors: Katakam Prasad V , Busija David W
Published: March 2022

Introduction:
Mitochondrial depolarization and subsequent generation of reactive oxygen species (ROS) in vascular smooth muscle cells (VSMC) trigger vasodilation by diazoxide, a putative mitochondrial K
ATP
channel (mitoK
ATP
) opener, via activation of ‘Ca
2+
-sparks’ (CS) and Ca
2+
-activated K
+
channels. It is unclear if mitochondrial depolarization, independent of ROS, promotes CS. In addition, the contribution to dilation of calcium events in endothelium following mitochondrial activation is unclear. Previously, we reported reduced vasodilation of cerebral arteries of insulin resistant (IR) Zucker obese (ZO) compared to lean (ZL) rats. Therefore, we examined the effect of BMS-191095 (BMS), a mitoK
ATP
opener that does not affect ROS generation, on cerebral arteries of Sprague-Dawley (SD) and ZL rats. In addition, we evaluated the impact of mitochondrial dysfunction due to IR in ZO rats.

Methods:
Fluorescence microscopy was used to measure the CS and global calcium (Fluo-4 AM), mitochondrial membrane potential (TMRE), ROS (mitoSOX), and nitric oxide (DAF) in segments of pressurized, cerebral arteries. Diameters were determined continuously with an automated system.

Results:
In SD arteries, BMS (50 umol/L) depolarized mitochondria without producing ROS. BMS also enhanced generation of CS (54±9 versus 117±18 sparks/min in response to vehicle and BMS respectively, p<0.05). Baseline CS activity (sparks/min) was reduced in ZO compared to ZL (156±21 versus 231±26, p<0.05). BMS and DZ responses were diminished in ZO (207±48 and 257±32, p=NS) versus ZL (318±54 and 366±63). In addition, BMS increased global calcium and nitric oxide production by endothelium.

Conclusions:
Mitochondrial depolarization induces Ca
2+
-sparks in VSM and increased global calcium in endothelium via ROS-independent mechanisms. Thus, mitochondria can be depolarized without an associated increase in ROS levels. In addition, mitochondrial dysfunction associated with IR impaired CS activity leading to reduced mitochondrial mediated vasodilation. Thus, even a relatively mild metabolic disease such as IR, is able to disrupt coupling between mitochondrial status and vascular tone.
Abstract 111: Cerebrovascular Remodeling In Diabetes: Relevance To Stroke
Authors: Prakash Roshini , Stern Javier E , El-Remessy Azza B , Fagan Susan C , Johnson Maribeth , Dore-Duffy Paula , Ergul Adviye
Published: March 2022

Background:
Diabetes is a major risk factor of stroke leading to the development of both large artery and lacunar infarcts associated with increased bleeding, and neurological and functional disability. We previously reported enhanced cerebral arteriogenesis in a mild and lean model of Type 2 diabetes. Here we hypothesize that cerebral neovascularization is regulated in a spatial manner in diabetes and vascular endothelial growth factor (VEGF) and peroxynitrite signaling are the underlying key regulators of increased remodeling.

Methods:
Neovascularization was assessed from brain, skeletal muscles and retina of control Wistar and diabetic Goto-Kakizaki rats. 3-dimensional reconstruction of the FITC stained vasculature were obtained by confocal microscopy and stereological parameters like vascular volume, density and surface area were measured. Unperfused vasculature was measured by immunostaining with Isolectin B4. Pericyte coverage was determined by nuclear staining (DAPI). VEGF and tyrosine nitration were evaluated by immunoblot and slot blot.

Results:
There was a progressive increase (rostral to caudal) in both cortical and striatal angiogenic parameters in the diabetic group. Cortical vascular density was more pronounced than the striatum in the diabetic group. Difference between FITC and Isolectin co-staining revealed that unperfused new vessels were prominent in the diabetic striatum. Endothelial cell number was markedly increased and pericyte/endothelial cell ratio indicating vascular maturity was significantly decreased in diabetes. Peripheral vascularization was impaired while increased in the retina. VEGF-A was greater in the microvessels but not macrovessels or brain homogenates devoid of vessels in diabetic animals. Diabetic microvessels also exhibited greater tyrosine nitration.

Conclusion:
Diabetes uniquely mediates cerebral neovascularization while regresses the peripheral vasculature. There exist spatial and regional differences in the diabetic brain that have relevance to neurovascular injury in stroke. Excessive neovascularization, a large pool of unperfused microvessels and reduced pericytes compromise the blood brain barrier and lead to increased bleeding during reperfusion injury in diabetes. N=4-10
*
p≤ 0.05,
**
p≤ 0.005
Abstract 112: Cigarette Smoke Directly Produces a Pro-inflammatory/matrix remodeling Phenotype in Cerebral Vascular Smooth Muscle Cells via KLF4: A Potential Mechanism for Cerebral Aneurysm Pathogenesis
Authors: Ali Muhammad , Yu Zaifang , Jabbour Pascal M , Tjoumakaris Stavropoula I , Gonzalez L. Fernando , Rosenwasser Robert H , Koch Walter J , Dumont Aaron S
Published: March 2022

Cigarette smoke is one of the most significant environmental risk factor for cerebral aneurysm formation. Inflammation, matrix degradation and vascular smooth muscle cell phenotypic modulation are thought to be important in aneurysm pathology yet molecular pathogenic mechanisms are unknown. We investigated the role of cigarette smoke in producing phenotypic modulation and inflammation in cerebral vascular smooth muscle cells (VSMCs) focusing on a potential pivotal role of the transcription factor, KLF4.

Methods:
Rat cerebral VSMCs were treated with Cigarette Smoke Extract (CSE) at 4 and 40 ug/ml for 4, 24 and 48 hours. The level of water soluble components of cigarette smoke and nicotine levels present in the CSE overlap with plasma levels of these constituents in human smokers. SMC marker genes (SM-alpha-Actin, 22-alpha and MHC), transcription co-activator, Myocardin, KLF4 and inflammatory/matrix remodeling genes (MMP-2, 3, 9, VCAM-1, MCP-1, and iNOS) were measured using qPCR. siRNA against KLF4 and non-specific siGFP were transfected in cultured VSMCs to examine a potential critical role for KFL4 in this process. As part of in vivo experiments, Pluronic Gel (40% w/v) containing 0.2 - 0.8 mg/ml CSE was applied to the adventitial surface of rat carotid arteries for 24-48 hours.

Results:
CSE significantly induced KLF4 expression at 4 hours (p<0.05 vs. baseline) preceding phenotypic modulation of VSMCs. CSE directly produced marked phenotypic modulation with decreased expression of SMC marker genes and myocardin while markedly increasing expression of inflammatory/matrix remodeling genes (p<0.05 vs. baseline). Strikingly, this profound phenotypic modulation was reversed with siKLF4. Similarly, decreased expression of marker genes and Myocardin with concomitant upregulation of KLF4 and inflammatory/matrix remodeling genes was noted following in vivo pluronic gel application containing CSE. The most notable increase was noted in MMPs, MCP-1, IL-1 and TNF-alpha expression (all p<0.05 vs. control).

Conclusions:
Cigarette smoke directly produces marked phenotypic modulation of cerebral vascular smooth muscle cells in vitro and in vivo promoting a pro-inflammatory/matrix remodeling phenotype. These effects appear to be mediated via KLF4. Inflammation, accelerated matrix remodeling and VSMC phenotypic modulation are implicated in human cerebral aneurysms. The molecular mechanisms activated by cigarette smoke outlined here may have critical implications for human cerebral aneurysm pathogenesis and may represent important targets for future therapy. Fig: Gene Expression.
Abstract 123: Predictors Of Unfavourable Outcome In Medically Treated Symptomatic Intracranial Atherosclerotic Disease.
Authors: Kate Mahesh , P.N Sylaja , Kesavdas Chandrasekar , Thomas Bejoy
Published: March 2022

Background:
Patients with symptomatic intracranial atherosclerotic disease (sICAD) have a 12-14 % annual risk of stroke. The aim of the study was to evaluate the natural history and outcome of patients with sICAD treated medically.

Methods:
The study population consisted of first ever TIA or stroke patients presenting to this quaternary care centre during the period of January 2008 to March 2011, who on vascular imaging have isolated intracranial atherosclerosis as cause of their symptoms in whom other potential causes have been ruled out and have a follow up of minimum 90days after onset of index event. Unfavourable outcome was defined as presence of TIA, stroke, acute coronary event or vascular death and modified Rankin scale ≥ 3.

Results:
Fifty three (11.8 %) of the 449 first ever ischemic stroke patients had sICAD. The risk of stroke or TIA in the sICAD territory was 20%, 26.7%, 28.9%, 31.1% in first 7days, 30 days, 90days and 1year respectively. Five (11.1%) patients had cardiovascular events, of these more than two-thirds of these events occurred after 90days of index event and were responsible for 50% mortality in the study. The predictors of unfavourable outcome were presentation as limb weakness (85.7% vs. 58.8%, hazard ratio 1.5; 95%CI, 0.05-0.9; p=0.04), NIHSS at admission ≥8 (50% vs. 5.9%, hazard ratio 8.5; 95%CI, 0.007-0.5; p=0.02), MRI with multiple DWI lesions ( 65.4% vs. 26.7% ;95%CI, 0.04-0.7; p=0.01) and angiography suggestive of diffuse atherosclerosis ( 50% vs. 11.8% ; 95%CI, OR 0.02-0.7 ; p=0.009). On stepwise multiple regression independent variables for unfavourable outcome were NIHSS at admission≥8 (p=0.001, t=3.5), multiple DWI lesion on MRI (p=0.04, t=2.9) and diffuse atherosclerosis on angiography (p=0.006, t=2.9).

Conclusion:
The patients with sICAD have a very high risk of stroke or TIA in the first 30days even on aggressive medical treatment. Cardiac events are an important cause of mortality and needs close follow-up.
Abstract 125: A Randomized Trial Comparing Primary Angioplasty versus Stent Placement for Symptomatic Intracranial Stenosis
Authors: Suri M Fareed K , Chaudhry Saqib A , Siddiq Farhan , Majidi Shahram , Rodriguez Gustavo J , Qureshi Adnan I
Published: March 2022

Introduction:
The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) was prematurely terminated due to excessively high rate of stroke and death in patients randomized to intracranial stent placement. Equivalent results with primary angioplasty in several uncontrolled studies will continue to raise the question that a policy of mandatory stent placement may have led to a higher peri-procedural stroke and death without a clear evidence of incremental benefit.

Methods:
The primary aim of the study is to compare the clinical and angiographic efficacy of primary angioplasty and angioplasty followed by stent placement in preventing restenosis, stroke, requirement for second treatment, and death in patients with symptomatic intracranial stenosis. The study prospectively evaluated acute,1-month, 6 month, and 1-year efficacy and safety of the two existing neurointerventional techniques for treatment of moderate intracranial stenosis (stenosis ≥50%) with documented failure of medical treatment or severe stenosis (≥70%) with or without failure of medical treatment.

Results:
A total of 18 patients were recruited in the study; mean age [±SD] was 64.7±15.1 years, 12 were men. Of these 18, 10 were randomized to primary angioplasty and 8 were randomized to angioplasty followed by self expanding stent. The technical success rates of intracranial angioplasty and stent placements defined as ability to achieve <30% residual stenosis when assessed by immediate post-procedure angiography was 5 of 10 and 5 of 8 patients respectively. The total fluoroscopic time (mean [±SD] was lower in patients undergoing primary angioplasty 37 [±11] mins versus those undergoing angioplasty followed by self expanding stent 42 [±9] mins, p=.309. The 1 month stroke and death rate was very low in both patient groups (1 of 10 versus none of 8 patients).

Conclusions:
The trial suggests that a randomized trial comparing primary angioplasty to angioplasty followed by stent placement is feasible. The immediate procedural outcomes with primary angioplasty are comparable to stent placement and warrant further studies.
Abstract 136: Treatment of Basilar Artery Occlusion Without Time Constraints: Clinical outcomes, safety and predictors of favorable results
Authors: Starr Matthew T , Zaidi Syed F , Jumaa Mouhammmad A , Reddy Vivek K , Hammer Maxim D , Jankowitz Brian T , Horowitz Michael B , Wechsler Lawrence R , Jovin Tudor G
Published: March 2022

Background:
Because acute stroke due to basilar artery occlusion (BAO) without recanalization (spontaneous or treated) carries a poor prognosis, recanalization treatment is increasingly initiated beyond conventional time windows. We report our experience with endovascular treatment for this condition when patients are selected without regards to time window considerations.

Methods:
A retrospective review of a prospectively acquired database comprising 667 patients treated with endovascular therapy for acute stroke due to large vessel intracranial occlusions from 2000 to date. All patients presenting with BAO were included. Selection of patients occurred at the discretion of the treating stroke neurologist not necessarily based on time but based on clinical and imaging characteristics that led to the belief in a reasonable chance of a good outcome. Successful recanalization was expressed as Thrombolysis in Myocardial Infarction (TIMI) score ≥ 2. Favorable outcomes were considered 3 month modified Rankin Score (mRS) ≤ 2. Any parenchymal hematoma (PH) was considered symptomatic.

Results:
We identified 85 patients. Median age: 63. Median admission NIHSS: 18 (IQR 11-29). Male sex: 57.6%. Median time from last seen well (TLSW) to groin puncture: 774 min (12.9 hrs) (IQR 324min-2262min). Median procedure duration: 105.5 min (IQR 67min-145min). 18% of patients received IV tPA. TIMI 2-3 recanalization occurred in 87% of patients treated. Favorable outcomes were noted in 34% of patients. mRS of 3 was achieved in 9.4%. Mortality was 46%. PH was noted in 8.2% of patients. Treatment modalities included IA lytics (56.4%), MERCI device (39%), Penumbra (6%), Manual Aspiratoin Thrombectomy (27%), Stenting (42%), Angioplasty (46%). In 76.4% of patients the procedure was carried out in intubated state. In multivariate analysis, age (OR 0.94, P=0.007, 95% CI 0.89-0.98), successful recanalization (OR 16, P=0.027, 95% CI 1.38-197.56) and admission glucose (OR 0.98, P=0.033, 95%CI 0.97-0.99) were found to be significantly associated with favorable outcomes. Of note TLSW to treatment initiation was not found in univariate or multivariate analyses to be significantly associated with favorable outcomes.

Conclusions:
This single center experience indicates that endovascular treatment in selected patients with BAO without time window considerations is associated with similar rates of symptomatic hemorrhage (SICH) and rates of favorable outcomes compared to available literature data where selection is based on strict time windows. The role of time as selection criteria for treatment of BAO should be clarified by future prospective trials.
Abstract 14: Fine Mapping Study Revealed Novel Candidate Genes for Carotid Intima-Media Thickness in Dominicans
Authors: Wang Liyong , Beecham Ashley , Dong Chuanhui , Gardener Hanna , Blanton Susan , Rundek Tatjana , Sacco Ralph
Published: March 2022

Background:
Carotid intima-media thickness (CIMT) is a subclinical measure for atherosclerosis, the major underlying cause for stroke and other cardiovascular events. Previously, we have mapped quantitative trait loci (QTLs) for CIMT to chromosomes 7p (MLOD=3.1) and 14q (MLOD=2.3) in 100 extended Dominican Republican (DR) families.

Methods and Results:
To identify the genetic variations accounting for CIMT variability at those QTLs, we surveyed the one-LOD-unit-down linkage regions using >2,000 tagging single nucleotide polymorphisms (SNPs). Family-based association tests were performed in the 100 DR families (N=1372) used in the original linkage study, adjusting for significant covariants. Promising SNPs were further examined in the population-based NOMAS subcohort comprised of DR subjects only (N=553). Evidence for association (P<0.001) was found in multiple genes (
ANLN
,
AOAH, FOXN3, CCDC88C, PRiMA1, and
an intergenic SNP rs1667498 near
FLRT2)
with the strongest association at PRiMA1 (P=0.00007, which remained significant after adjusting for multiple testing). The association at these genes, except for PRiMA1, was driven by families with evidence for linkage (53 and 51 families for the 7p and 14q QTL, respectively; P= 0.00004∼0.00092 and 0.13∼0.80 in families with and without evidence for linkage, respectively), suggesting that these genes might collectively account for the QTLs delimited in our family data set. On the other hand, the association at
PRiMA1
is significant in both family subsets (P=0.002 and 0.019 in families with and without evidence for linkage, respectively). The association at PRiMA1, but not at other genes, was replicated in the NOMAS DR subcohort (P=0.047), supporting a robust association at
PRiMA1
.

Conclusions:
We identified several candidate genes for CIMT in Dominican Republicans. Some of the genes manifest genetic effects within a specific subset of families and others can be generalized in additional samples. Future studies are needed to further elucidate the contribution of these genes to atherosclerosis.
Abstract 140: National Trends in Utilization and Outcomes of Endovascular Treatment in Acute Ischemic Stroke Patients
Authors: Hassan Ameer , Chaudhry Saqib , Suri Fareed , Qureshi Adnan
Published: March 2022

Background:
With the availability of several new devices for mechanical thrombectomy after recent approvals by the Food and Drug Administration, the outcomes of patients undergoing endovascular treatment for acute ischemic stroke are expected to improve in United States.

Objective:
To evaluate trends in utilization of endovascular treatment and associated rates of death and disability among acute ischemic stroke patients over six years.

Methods:
We obtained data for patients admitted to hospitals in the United States between 2004 to 2009 with a primary diagnosis of ischemic stroke using a large national database. We determined the rate of utilization of endovascular treatment. Outcomes were classified as minimal disability, moderate to severe disability, and death based on discharge disposition.

Results:
Of the 670,069 patients with ischemic stroke, 72,342 (10.8%) received intravenous thrombolytic treatment, 18,229 (2.72%) had endovascular thrombolysis. Patients with endovascular treatment comprised 0.35% of ischemic strokes in 2004 vs 4.95% in 2009 (p < 0.001). The estimated number of patients undergoing endovascular treatment increased by 1,519% (362 to 5502) despite a 324% increase in patients receiving intravenous thrombolytic. The rates of intracranial hemorrhage remained unchanged throughout the 6 years. There was no significant difference in all age groups. The interaction between endovascular treatment among all ischemic stroke patients for predicting in-hospital mortality significantly improved (p <0.02).

Conclusion:
There has been a significant increase in proportion of acute ischemic stroke patients receiving endovascular treatment over the last 6 years with significant reduction in in-hospital mortality.
Abstract 145: Dietary Fish and Omega-3 Intake and Risk of Ischemic Stroke: The REGARDS Study
Authors: Nahab Fadi , Le Anh , Judd Suzanne , Frankel Michael R , Ard Jamy , Kleindorfer Dawn O , Howard Virginia J
Published: March 2022

Background:
We previously reported that persons living in the Stroke Belt were more likely than non-Belt persons to consume ≥2 weekly servings of fried fish but less likely to meet the AHA recommendation of ≥2 weekly servings of nonfried fish. The objective of this report was to evaluate whether the differential consumption of fish contributes to the geographic and racial disparities in stroke.

Methods:
REGARDS is a national cohort study that recruited 30,239 participants (2003-2007) ≥45 years with oversampling from the southeastern Stroke Belt and African Americans (AAs). Centralized phone interviewers obtained medical histories and in-home examiners obtained physical measures. Dietary data were collected using the self-administered Block98 Food Frequency Questionnaire (FFQ). After excluding the top and bottom 1% of total energy intake, individuals who did not answer 85% or more of the FFQ, and those with a history of stroke or TIA at baseline, the analysis cohort included 20,480 participants. Incident stroke was defined as first stroke occurrence over 5.0 years of follow-up.

Results:
There were 549 incident strokes including 501 ischemic strokes. After excluding hemorrhagic strokes and stratifying by race, white participants eating ≥2 servings per week (vs <2/week) of fried fish were at a significantly increased risk of ischemic stroke after adjusting for demographic, SES, physical activity, BMI, caloric intake and Framingham stroke risk score factors (HR 2.80, 95% CI 1.12 to 6.96); there was no association found among AAs. Compared with participants in the lowest quartile of dietary n-3 intake (mean intake 0.74 g/day), participants in the highest quartile (mean intake 2.8 g/day) had a 29% reduction in ischemic stroke risk after adjusting for demographic factors and caloric intake (HR 0.71, 95% CI 0.52 to 0.97); when stratified by race, AAs in the highest quartile of n-3 intake had a 49% reduction in ischemic stroke risk compared with the lowest quartile after adjusting for demographic factors and caloric intake (HR 0.51, 95% CI 0.30 to 0.88).

Conclusions:
Fried fish intake of ≥2 servings (vs <2) per week was associated with more than twice the risk of ischemic stroke among whites. High dietary n-3 intake may reduce the risk of ischemic stroke especially among AAs and warrants further study in primary stroke prevention. Differential consumption of fish may contribute to geographic and racial disparities in ischemic stroke.
Abstract 148: Efficacy and Safety of Rivaroxaban Compared with Warfarin Among Elderly Patients with Nonvalvular Atrial Fibrillation in the ROCKET-AF Trial
Authors: Halperin Jonathan L , Wojdyla Daniel , Piccini Jonathan P , Lokhnygina Yuliya , Patel Manesh R , Breithardt Gunter , Singer Daniel E , Becker Richard C , Hacke Werner , Paolini John F , Nessel Christopher C , Mahaffey Kenneth W , Califf Robert M , Fox Keith A
Published: March 2022

Background:
Nonvalvular atrial fibrillation (AF) affects 5-10% of people over 75 years of age, in whom the risk of thromboembolism is higher than in younger individuals. Although warfarin protects against ischemic stroke, many patients cannot sustain treatment because of bleeding, drug interactions and coagulation monitoring. The oral Factor Xa inhibitor, rivaroxaban, displayed noninferior efficacy and safety as an alternative anticoagulant in the ROCKET-AF trial (median age 73 years). This analysis compares these treatments in patients >75 years.

Methods:
The ROCKET-AF trial (n=14,264) included 6,229 patients >75 years of age with AF and at least 1 additional stroke risk factor randomized to adjusted-dose warfarin (target INR 2.0-3.0) or fixed-dose rivaroxaban (20 mg daily; 15 mg daily if baseline creatinine clearance <50 ml/min), double-blind. The primary endpoint was all strokes (ischemic or hemorrhagic) and systemic embolism analyzed during the on-treatment period and according to intention-to-treat (ITT).

Results:
Compared to younger patients, those ≥75 years at baseline had a mean CHADS
2
score of 3.7 vs. 3.3, 46 vs. 35% were female, and 42 vs. 65% had prior stroke/TIA. During 9,247 patient-years exposure, 429 stroke or systemic embolic events occurred among patients >75 years old. Long-term tolerability was similar between treatments; 59.4% of patients on warfarin (W) and 59.3% on rivaroxaban (R) completed the trial taking assigned treatment, compared with 69.9 and 68.7% in younger patients. The mean INR in the warfarin group (2.44, SD=0.86) was within target range for 56.9% (SD=21.6) of follow-up, compared to 53.9% (SD=20.9) in younger patients. The
table
compares annualized event rates for patients <75 and >75 years of age at entry. The on-treatment thromboembolism rates of 1.78 vs. 2.65%/year with rivaroxaban and warfarin, respectively (HR 0.67; 95% CI 0.51-0.89) were not much higher than in younger patients. Older patients had higher rates of (mostly non-major) clinically relevant bleeding (interaction
p
=0.009), but rates with warfarin and rivaroxaban were comparable.

Conclusions:
In elderly, high-risk patients with AF, once-daily oral rivaroxaban without coagulation monitoring or dose adjustment performed favorably compared to adjusted-dose warfarin as it did in the overall ROCKET-AF population. 1
Abstract 153: Long-term Monitoring For Paroxystic Atrial Fibrillation In Cryptogenic Stroke: Preliminary Results Of The Surprise Study
Authors: Christensen Louisa M , Krieger Derk , Højberg Søren , Pedersen Ole D. , Karlsen Finn Michael , Worch René , Nielsen Henrik , Ægidius Karen , Rosenbaum Sverre , Marstrand Jakob , Christensen Hanne
Published: March 2022

The SURPRISE project aims at estimating the frequency and the burden of paroxystic atrial fibrillation in patients with apparent cyptogenic minor stroke or TIA. Long term monitoring by use of a implanted Reveal XT ® is used with the aim of obtaining complete data on arrhythmia long term after minor stroke/TIA. In short, patients with cryptogenic (including no history of AF, and no signs of AF on telemetry during hospital stay) minor stroke or DWI-positive TIA, modified Rankin Scale ≤ 2, and no contraindications to anticoagulation treatment are included after informed consent from a comprehensive stroke unit. A Reveal XT®, an atrial fibrillation sensitive loop-recorder, is implanted subcutaneously, and patients are monitored for up to 3 years and followed up clinically by regular visits. Arrhythmia episodes are adjudicated by a senior consultant cardiologist specialized in electrophysiology. Primary endpoints of the study are 1) episodes AFIB and 2) burden of AFIB. Further 1) persisting AF and 2) recurrent stroke/TIA, and 3) treatment change to anticoagulation based on monitoring events. The study aims at enrolling a total of 100 patients, which is expected before end 2011.

Results
Until today (august 15
th
2011) we have included 52 patients; 43 are so far implanted and actively transmitting data. In 8 patients (18.6 %) AFIB has been documented on monitoring and have consequently been anticoagulated. No recurrent events have occurred so far. Long term monitoring was instrumental in treatment change in 18.6 % of patients. AF patients have a mean age of 64.5 years vs 57.5 years in no AF patients (p= 0.017) AF patients also have a higher CHADS2 score 3.25 vs 2.34 (p=0.013) The average time from stroke onset to first recorded event of AFIB is 133 days (see fig.1) These preliminary data suggest that paroxystic AF is frequent in cryptogenic stroke even after telemetry and may occur after a long free interval. Long term monitoring frequently results in change of treatment. Older patients and patients with more risk factors are more likely to have paroxystic AF. As anticoagulant treatment improves prognosis in patients with AF after stroke, better identification of patients with AF is likely to reduce the burden of recurrent stroke.
Abstract 16: Pattern Of Brain Function Change In Multiple Regions Predicts Mitigation Of Spasticity Following Intensive Arm Neurorehabilitation In Chronic Stroke
Authors: Pundik Svetlana , Hrovat Ken , Litinas Krisanne , McCabe Jessica , Rogers Jean , Holcomb John , Daly Janis J
Published: March 2022

Background:
Spasticity can prevent productive practice of skilled movement that should occur during neurorehabilitation of coordinated arm movements after stroke. Studies showed that spasticity could be reduced following an intervention that inhibited activation of the contralesional primary motor region (M1) using non-invasive transcranial magnetic or electric stimulation. However, there is little understanding of how the mitigation of spasticity might be controlled by the multiple sensorimotor control brain regions. Therefore, the aim of this study was to evaluate the change in activation patterns of multiple sensorimotor regions that predict the mitigation of spasticity, in response to intensive upper limb neurrehabiltiation.

Methods:
Twenty three stroke subjects (>6 months after stroke) with persistent arm motor deficits were treated with intensive upper extremity rehabilitation (5 hours/day, 5 days/week for 12 weeks). Baseline and post-rehab evaluation consisted of three measures: 1) functional magnetic resonance imaging (fMRI) during a shoulder/elbow reach task for the paretic arm, 2) a skilled motor function (Arm Motor Assessment test (AMAT)), and 3) spasticity (Modified Ashworth Scale(MAS)). Volume of brain activation (voxel count) during the reach task was calculated for sensory and motor control regions using SPM05 (London, UK) and in-house software in MATLAB (Natick, MA). Paired t-test analysis was conducted for pre- vs post-treatment comparisons. Multiple linear regression analysis was conducted, where post-rehab AMAT was the dependent variable, the co-variate was pre-rehab score, and the predictors were change from pre- to post-rehab in voxel count in bilateral M1, somatosensory (SS), posterior parietal (PP), lateral premotor (LPM) and supplementary motor (SMA) areas.

Results:
Subject characteristics were as follows: mean age, 56.3 ±12.8years; 41%, female; and 1.8±1.1 years after first ever stroke. Change in the activation pattern in a number of regions significantly predicted mitigated spasticity (R2=.86). Specifically, in response to treatment, increased activation, in ipsilesional SMA (p=.002) and contralesional M1 (p=.002), predicted mitigated spasticity. Reduction in activation volume, in ipsilesional PP region (p=.0009), contralesional SS (p=.008) and SMA (p=.006), predicted mitigated spasticity. AMAT score improved from 1636.63±668.41 to 1213.67±6643.79 seconds (p<.0001) and MAS scores improved from 6.81±2.75 to 1.86±1.49 (p<.0001).

Conclusions:
A specific pattern of functional brain change across multiple regions predicted mitigation of spasticity following neurorehabilitation; skill functional recovery occurred, as well. This information could be used in constructing study design for future research that would investigate brain training to mitigate spasticity and improve skilled functional task performance.
Abstract 172: Cost-Effectiveness of Dabigatran Compared with Warfarin for Secondary Stroke Prevention in Patients with Atrial Fibrillation and Prior Stroke or Transient Ischemic Attack
Authors: Kamel Hooman , Johnston S. Claiborne , Easton J. Donald , Kim Anthony S
Published: March 2022

Background:
The cost-effectiveness of dabigatran for secondary stroke prevention in patients who present with atrial fibrillation (AF) and stroke or transient ischemic attack (TIA) has not been directly assessed.

Methods:
A Markov decision model was constructed (Figure 1) using data from a substudy of the Randomized Evaluation of Long-Term Therapy (RE-LY) trial, other trials of warfarin therapy for AF, and the published cost of dabigatran. We compared two treatment strategies: adjusted-dose warfarin therapy with an international normalized ratio (INR) target of 2 to 3, versus dabigatran 150 mg twice daily. The target population was a cohort of patients aged 70 years and older with non-valvular AF, prior stroke or TIA, and no contraindication to anticoagulation. The model outputs were costs in 2010 U.S. dollars and quality-adjusted life-years (QALYs).

Results:
In the base case, quality-adjusted life expectancy was 4.36 QALYs with dabigatran compared with 4.04 QALYs with warfarin. Dabigatran provided 0.34 additional QALYs at a cost of $9,500, yielding an incremental cost-effectiveness ratio of $28,000. In sensitivity analyses (Figure 2), the cost-effectiveness of dabigatran was influenced by patients’ age, the cost of dabigatran, the relative risk of stroke using dabigatran compared with warfarin, and the quality of INR control achieved with warfarin therapy.

Conclusions:
Dabigatran appears to be cost-effective relative to warfarin for stroke prevention in patients with AF and prior stroke or TIA. Our analysis is limited by its reliance on data from a substudy of a single randomized trial, and our results may not apply in settings with atypically good INR control using warfarin.
Abstract 173: Patterns and Predictors of Emergency Medical Services Pre-Notification of Potential Stroke Cases in the United States: Findings from GWTG-Stroke
Authors: Lin Cheryl , Peterson Eric D , Smith Eric E , Saver Jeffrey L , Liang Li , Shah Bimal R , Xian Ying , Olson DaiWai M , Hernandez Adrian F , Schwamm Lee H , Fonarow Gregg C
Published: March 2022

Background:
Emergency medical services (EMS) pre-notification of potential stroke arrivals has been recommended as a means of improving stroke evaluation and treatment times. However, little is known as to how frequently EMS pre-notification is being applied in the US, how use varies by hospital/state/region, and factors associated with EMS pre-notification.

Methods
:
Acute ischemic stroke patients transported by EMS to 1585 GWTG-Stroke hospitals from April 2003 to March 2011 were studied. Patient and hospital characteristics associated with EMS pre-notification were analyzed with multivariate GEE models.

Results:
Of 371,988 acute ischemic stroke patients transported by EMS, pre-notification occurred in 249,197 (67.0%).

Among hospitals with at least 10 EMS arriving stroke patients (n=1395), the median rate of pre-notification was 70.0 (25
th
-75
th
34.0-92.9%, range 0%-100%). There was significant variation in pre-notification by state ranging from a low of 19.7% in Washington DC to a high of 93.4% in Montana. EMS pre-notification rates non-significantly increase over time, 58.0% in 2003 to 67.3% in 2011, p=0.10. Patient factors independently associated with EMS pre-notification include younger age, white race, no diabetes, and history of atrial fibrillation (Table). Hospital factors included region (West and Midwest), non-academic status, and higher annual IV tPA volumes (Table).

Conclusions:
EMS pre-notification is provided in only two-thirds of EMS arriving GWTG-Stroke patients ultimately diagnosed with acute ischemic stroke in the US and varies substantially by hospital, state, and region in the US. Older patients, non-white, and those with certain comorbid conditions were significantly less likely to have EMS pre-notification. These findings suggest there are further opportunities to improve EMS pre-notification rates.
Abstract 180: Are Coil Compaction And Aneurysmal Growth Two Distinct Etiologies Leading To Recurrence Following Endovascular Treatment Of Ruptured Intracranial Aneurysms?
Authors: Abdihalim Mohamed , Wanatabe Masaki , Chaudhry Saqib A , Jagadeesan Bharati , Suri M. Fareed K , Qureshi Adnan I
Published: March 2022

Background:
Recurrence following endovascular treatment of intracranial aneurysm can be seen in one of four intracranial aneurysms. The recurrence is attributed to either coil compaction or aneurysm growth but these processes have not been studied if these processes are distinct processes or if they act in concert.

Methods:
Aneurysm recurrence was identified by an independent review of immediate post-procedure and follow-up angiographic images of consecutive patients who had endovascular treatment of intracranial aneurysms at two medical centers from September 2006-April 2010. The voxel size of the coil mass and aneurysm sac, and the adjacent parent artery were measured using the Analyze Software (Mayo Clinic). To avoid errors associated with absolute measurements on different images, the voxel sizes of the coil masses and aneurysm sac were expressed as a ratio to the voxel sizes of the parent vessel diameter on immediate post-procedure and follow-up angiograms. Increase of aneurysm area or decrease in coil mass of 30% or greater on follow-up angiogram was used to define “aneurysm growth” and “coil compaction”, respectively

Results:
Based on our criteria, a total of 29 out of 201 patients had aneurysm recurrence at mean follow of 9.1 months (SD 6.3). Of these, 11 patients had coil compaction and 18 had aneurysm growth. There were no patients with both aneurysm growth and coil compaction. The rate of aneurysm growth and coil compaction among patients who were treated for ruptured intracranial aneurysms was 11% and 7% respectively. There were no events of new aneurysmal rupture in either the 11 patients who had coil compaction or the 18 patients who had aneurysm growth over a mean follow-up period of 22 months (range of 9-42 months). Retreatment was performed in 15 of the 18 patients with aneurysm growth and 8 of the 11 patients with coil compaction. The 1 month stroke and death rate after retreatment was similar between patients with aneurysm recurrence due to coil compaction or aneurysm growth.

Conclusion:
Our study suggests that coil compaction and aneurysm regrowth are two distinct processes that can contribute to aneurysm recurrence. Further studies would have to identify whether each mechanism is associated with a differential risk of aneurysmal rupture.
Abstract 189: Analysis of Hypertension Associated Genetic Variants in Stroke Cases and Controls
Authors: Worrall Bradford B , Chen Fang , Chen Wei-Min , Hsu Fang-Chi , Southerland Andrew M , Meschia James F , Sharma Pankaj , Nalls Michael , Brown Robert D , Brott Thomas G , Hardy John , Singleton Andrew , Doheny Kimberley F , Laurie Cathy C , Gogarten Stephanie , Bookman Ebony B , Mirel Daniel B , Reiner Alex P , Kooperburg Charles , Carty Cara , Kene Keith L , Sale Michele M
Published: March 2022

BACKGROUND:
Recent genome-wide association studies (GWAS) have identified a number of novel SNPs associated with blood pressure and hypertension-related traits although studies were very large (approaching 80K participants) and effect sizes were modest with per allele effect sizes as small variants as a single millimeter of mercury difference in blood pressure. However, because hypertension is the most potent modifiable risk factor for ischemic stroke, lowering blood pressure by a few mm Hg can translate into measurable decrease in stroke risk.

METHODS:
We investigated 22 hypertension (HTN) associated SNPs in a case-control analysis of ischemic stroke in multiple stroke studies including the Siblings With Ischemic Stroke Study (SWISS), the Ischemic Stroke Genetics Study (ISGS), the Bio-Repository of DNA in Stroke (BRAINS), the Vitamin Intervention for Stroke Prevention (VISP) trial, and the Women's Health Initiative (WHI). SWISS/ISGS/BRAINS were analyzed together and included subtype information. Genotyping was funded through the individual studies, the Genomics and Randomized Trials Network (GARNET) consortium, and the SHARe (SNP Health Association Resource). All studies had both raw and imputed GWAS data. Analyses included the following phenotypes: all ischemic stroke, stroke subtypes, and age-at-stroke-onset and were stratified by race. Analyses were minimally adjusted for age, sex and principal components 1 & 2. Alpha was set at 0.05.

RESULTS:
Eleven of the SNPs from the HTN GWAS were associated with ischemic stroke in European ancestry from one or more of the study populations. Two SNPs on chromosome 12 and one on chromosome 21 were associated in multiple European ancestry cohorts. No SNP was associated in all studies. A SNP previously associated with HTN in African ancestry populations was associated with stroke in African-Americans. Analysis of subtypes found associations with small vessel disease and cardioembolic stroke but not large artery disease. The case-only age-at-stroke-onset analysis also found associations for the two SNPs on chromosome 12.

CONCLUSION:
These data suggest that candidate SNPs from a HTN GWAS may be associated with ischemic stroke and warrant further investigation. Racial differences were observed. Replication in populations from the other SiGN (Stroke Genetics Network), GENEVA (Gene Environment Association Studies) consortium, and the ISGC (International Stroke Genetics Consortium) studies are underway.
Abstract 1901: Perfusion Augmentation with the NeuroFlo Device in the SENTIS Trial: Cerebral Blood Volume Gradients Improve on Serial MRI
Authors: Liebeskind David S , Scalzo Fabien , Fong Albert K , Alger Jeffry R , Liu Songling , Dillon William P , Schellinger Peter D
Published: March 2022

Background:
Partial aortic occlusion may increase global cerebral blood volume (CBV) to enhance collateral perfusion in acute ischemic stroke. Therapeutic CBV changes in the ischemic territory may be difficult to detect with standard techniques if superimposed on global CBV alterations. We used CBV gradient maps to evaluate perfusion augmentation in the ischemic territory on serial MRI from baseline to 6 hours follow-up in subjects randomized to medical therapy with or without NeuroFlo treatment in the SENTIS trial.

Methods:
Perfusion MRI datasets in 54 subjects acquired at both baseline and 6 hours were prospectively collected at the core lab. Post-processing yielded CBV images and corresponding CBV gradient maps that depict regional variation of this perfusion parameter. Blinded imaging expert review was conducted to document presence, location, and other features of CBV gradients, with description of serial changes. Serial changes in CBV gradient maps were analyzed with respect to baseline demographics, medical history, treatment arm, and clinical outcomes (modified Rankin Scale, mRS) at day 90.

Results:
CBV gradient maps could be generated in 51 subjects with paired perfusion MRIs. CBV gradients were evident in 33/51 subjects (64.7%) at baseline, predominantly involving peripheral regions of the MCA territory. The presence of CBV gradients at baseline did not differ based on demographics, medical history, or treatment allocation. Overall, 12.1% revealed unchanged CBV gradients from baseline to 6 hours, with worsening in 18.2% and improvements in 69.7%. Alterations of CBV gradients on serial MRI were not related to baseline demographics or medical history in this cohort. Device therapy, however, was significantly associated with improvement of CBV gradients (p=0.005). Such early improvement in perfusion immediately post-procedure did not translate into statistically improved clinical outcomes (mRS 0-2) at day 90.

Conclusions:
CBV gradient maps can depict evolution of ischemia in acute stroke and therapeutic interventions such as perfusion augmentation. Treatment with the NeuroFlo device may improve perfusion in acute stroke, although other factors may subsequently influence clinical outcomes at day 90.
Abstract 192: Impact of Primary Stroke Center Certification on Rt-PA Utilization
Authors: Kleindorfer Dawn , Mullen Michael , Hogan Christopher , Adeoye Opeolu , Khatri Pooja , Mackey Jason , Jauch Edward
Published: March 2022

Introduction:
In 2003, the Joint Commission (JC) began certifying hospitals as Primary Stroke Centers (PSC). One of the key components of PSC certification is preparedness to administer rt-PA. Data regarding the impact of stroke center certification on rt-PA utilization is limited. We sought to compare rates of rt-PA use at JC-certified PSC’s to non-PSC’s, and to evaluate the impact of certification on rt-PA treatment rates, at the hospital level.

Methods:
This analysis utilized the MEDPAR database, which is a claims-based dataset containing every fee-for-service Medicare-eligible hospital discharge in the U.S. Ischemic stroke cases were defined via ICD-9 code of 433, 434, or 436. Thrombolysis use was defined as an ICD-9 procedure code of 99.1. Study interval was FY 2001-2010. Hospitals were stratified by ischemic stroke case volume. Date of original certification was obtained from the JC. For the temporal analysis, rt-PA utilization rates at each PSC were evaluated by quarter for three years pre- and post-certification. For comparison, every non-PSC was assigned a date for analysis, taken from PSC certification dates within the same case-volume class.

Results:
Of 3,275 acute care hospitals included in this analysis, 668 were JC certified PSCs. In FY 2010, the overall rt-PA utilization rate for the Medicare population was 2.2%, however utilization rates were significantly higher at PSC’s than non-PSC’s, 4.9% vs 1.5 %(P<0.0001). The difference between PSC’s and non-PSC’s rates was correlated with case load. Non-stroke centers admitting 10 or fewer stroke patients per quarter (n=1,058) treated 0.7% with rt-PA vs. low-volume PSCs (n=23) which treated 6.7% (p=0.0003). Non-PSC’s admitting more than 75 stroke patients per quarter (n=54) treated at a rate more similar to their PSC counterparts, (n=113), 3.2% vs. 4.6% (p=0.0031). The temporal relationship between certification and rt-PA utilization is displayed in the
>Figure
. Rt-PA utilization rates at PSC’s increased at a higher rate than non-PSC’s, 0.13% per quarter vs 0.02% per quarter (p<0.0001).

Discussion:
Compared to non-PSCs,JC certified PSCs utilize rt-PA on a higher proportion of IS patients, although the differences are the most striking in low-volume hospitals. Hospitals that sought PSC certification had similar baseline utilization rates to non-PSC’s. PSC’s increased rt-PA utilization rates prior to certification and this increase continued for three years post-certification. A limitation of this analysis is that “drip and ship” patients are not included for PSCs or non-PSCs.
Abstract 1947: Hispanics are Half As Likely As Others to Use EMS and Experience a Favorable 3-Month Outcome after Acute Ischemic Stroke in San Diego, California
Authors: Neil William P , Hemmen Thomas M , Raman Rema , Ernstrom Karin , Meyer Brett C , Bruce Nhu , Ovbiagele Bruce
Published: March 2022

Background:
Bridging racial-ethnic disparities in health care is a top public health priority. Hispanic Americans, the fastest growing segment in the United States, are at significantly higher risk of stroke than Non-Hispanic Whites, but may be less likely to use emergency medical services (EMS) in the event of an acute stroke. We compared pre-hospital/emergency department (ED) processes of care and 3-month outcomes by ethnicity in acute ischemic stroke (AIS) patients encountered in urban setting.

Methods:
Our University Stroke Program provides acute stroke care to five hospitals in San Diego that serve persons of varying race-ethnic and socioeconomic backgrounds. Socio-demographic, clinical, discharge and day-90 data on AIS patients presenting within 12 hours of ictus are prospectively collected in a database. For this study, specific variables of interest included use of EMS, time of stroke onset, time of arrival to the ED, and time of treatment decision and day-90 modified Rankin Scale (mRS) score. Wilcoxon Rank-Sum test was used for comparisons of continuous variables and Fisher’s Exact test was used for categorical variables. Favorable outcome was defined as day-90 modified Rankin Scale (mRS) score of 0-1. Outcome was adjusted for pre-specified covariates in a multivariable regression model.

Results:
There were 192 Hispanic and 925 non-Hispanic AIS patients encountered from June 2004 to March 2011. Hispanic patient differed from Non-Hispanic patients in mean age (65.6 vs. 70.9 years, p<0.01), female gender (57.8% vs. 44%, p<0.0001), and diabetes (37.5% vs. 20%, p <0.0001). Hispanic patients arrived by ambulance (vs. other arrival modes) less frequently (73.4% vs. 83.0%, OR 0.56; 95% CI: 0.38 - 0.81, p=0.003). There was no difference in time of stroke onset to arrival (252.7 vs. 279.5 p = 0.4) or treatment decision (351.6 vs. 320.02 minutes, p = 0.07). Favorable day-90 outcome was seen in 28.57% of Hispanic vs. 40.14% of Non-Hispanic AIS patients (OR 0.52, CI 0.28-0.96, p=0.04).

Discussion:
Individuals of Hispanic ethnicity in San Diego have about half the odds of a favorable outcome after acute ischemic stroke compared to others. Lack of EMS use by Hispanics is likely a major contributing factor. Development of strategies to boost EMS utilization may mitigate this worrisome stroke outcome disparity.