bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P90: Insulin-like Growth Factor-1-mediated Reduction of Stroke-induced Brain Infarction is Preceded by Improvement of Blood Brain Barrier Integrity and Inflammatory Cytokines
Authors: Bake Shameena , Sohrabji Farida
Published: July 2021

Background and Purpose:
Although insulin-like growth factor (IGF)-1 treatment has been shown to reduce stroke-induced infarct volume, the mechanisms underlying its neuroprotective actions are not fully understood. The present study tested the hypothesis that IGF-1 may regulate the neuroinflammatory cascade initiated by ischemic stroke, specifically, by promoting the integrity of the blood brain barrier.

Methods:
Middle-aged (10-12 month old) female rats were implanted with a cannula directed toward the lateral ventricle. One week later, animals were anesthetized using isoflurane and the middle-cerebral artery was occluded using an intraluminal suture maintained in place for 90 mins. IGF-1 or vehicle was delivered icv, via a mini-pump, following reperfusion. All animals were terminated at 4h or 24h post MCAo. Blood brain barrier permeability was determined using Evan’s blue extravasation and infarct volumes were determined from TTC-stained brain sections. Inflammatory cytokines were analyzed from brain lysates by ELISA.

Results:
IGF-1 treatment to middle-aged females resulted in a 39% reduction in infarct volume when measured 24h post MCAo, confirming the neuroprotective action of this peptide hormone. In order to assess the effects of IGF-1 on early stroke induced effects, we next determined blood brain permeability 4h post stroke as well as the expression of cytokines in the ischemic hemisphere. IGF-1 treatment resulted in a significant reduction of blood brain barrier permeability at 4h post-stroke compared to vehicle treated animals. Moreover, multiplex cytokine analysis showed that IGF-1 significantly reduced inflammatory markers such as IL-6, IFN-gamma, TNF-alpha, eotaxin, GM-CSF. Brain infarct volume at 4h was similar in both IGF-1 and vehicle groups, indicating that the effects of IGF-1 on inflammatory markers precede its effects on infarct volume. IGF-1 also suppressed IL-6, MIP-2, GRO-KC, MCP-1, EGF and MIP-1-alpha expression at 24h post stroke, indicating a persistent anti-inflammatory effect for this growth factor.

Conclusions:
The above findings support the hypothesis that IGF-1 has unique anti-inflammatory action in the aging female brain, and suggest that brain endothelial cells may be a primary target of IGF-1.
Abstract 103: MR Perfusion Lesions in Minor Stroke and TIA Patients Predict New Brain Infarction at 7-days
Authors: Lee Jun , Ke Michael , Mlynash Michael , Mann Sharan , Inoue Manabu , Kim Na-Young , Cereda Carlo , Albers Gregory , Olivot Jean-Marc
Published: July 2021

Background:
Although DWI-positive patients who present with transient symptoms have higher day-7 stroke rates than DWI-negative cohorts, little is known about the outcomes of TIA patients with focal perfusion lesions. The aim of the current study is to determine the day-7 recurrent stroke rate in TIA/minor stroke patients who have perfusion lesions on baseline MRI.

Methods:
Consecutive TIA and minor stroke (NIHSS < 4) patients who underwent baseline DWI and perfusion imaging as well as day-7 follow-up MRI with DWI and FLAIR at Yeungnam University Stroke Center in Korea were enrolled. Two perfusion parameters (Time to Peak and Mean Transit Time), DWI, ADC and FLAIR sequences were reviewed by 2 raters blinded to clinical outcomes. New brain infarction was defined by the presence of a new lesion on day-7 DWI and FLAIR. Symptomatic carotid and intracranial stenosis was assessed on baseline MRA. New neurological symptoms that occurred within 7 days were recorded.

Results:
Sixty-four patients met the inclusion criteria. Mean age was 64±13 years. Median ABCD2 was 4 (IQR: 3-5). At baseline, perfusion lesions were identified in 30 (47%), DWI lesions in 24 (38%) and symptomatic carotid and/or intracranial stenosis in 22 (34%) patients. Nine patients (14%) developed a new brain infarction on day-7 MRI, and all 9 patients had a baseline perfusion lesion. Thus, the rate of new brain infarction in patients with perfusion lesions at baseline was 30% (9/30). Of the 9 patients with new infarcts, 7 (78%) were clinically symptomatic, 5 (56%) had a negative baseline DWI, and 6 (67%) had normal vessel imaging.

Conclusion:
Our data suggest that the identification of a focal perfusion lesion during the imaging evaluation of TIA or minor stroke predicts a high rate of recurrent stroke within 1 week, even in the absence of identifiable vessel stenosis or DWI positivity on initial MRI.
Abstract 120: Association Between Hospital Process Performance and Favorable Outcomes Among Patients With Acute Ischemic Stroke
Authors: Li Zixiao , Wang Yilong , Zhao Xingquan , Wang Chunjuan , Wang Yongjun
Published: July 2021

Background:
Guideline recommended care processes are increasing being employed to measure hospital quality of stroke care; however, data regarding the association between hospital process performance and outcomes are unclear in China. We use the China National Stroke Registry (CNSR) to evaluate whether hospital’s overall composite guideline adherence was associated with observed and risk-adjusted 3 months favorable outcomes rates after stroke.

Methods:
An observational analysis of hospital care in 132 secondary and tertiary hospitals of 12 173 patients with acute ischemic stroke enrolled in the CNSR between 2007 and 2008. Thirteen performance measures including ten Get With The Guidelines-Stroke and 3 Chinese Neurology Association guideline-recommended interventions were adopted to measure hospital process performance for stroke care. The overall composite adherence rates of these performance measures were also calculated and divided into two levels according to median value. The relationship between hospital process performance for stroke care and three months favorable outcomes (defined as mRS 0-2), after stroke were analyzed using univariate analysis and generalized estimating equations.

Results:
Overall, the 13 guideline-recommended performance measures were adhered to 69.3% if eligible instances. However, composite adherence performance varied widely (composite adherence scores from the lowest to highest hospital, 13.2% vs 90.2%). High composite guideline adherence rate was significantly associated with the 3-months favorable outcomes, with observed 3-months favorable outcomes increasing from 48.0% for the low adherence rate to 52.0% for the high adherence rate (OR 0.884, 95% CI 0.82-0.95, P=0.001). After adjustment of patients and hospitals’ characteristics, high composite adherence scores of hospitals had a positive impact on the 3-months favorable outcomes (B value 0.169 P=0.02).

Conclusions:
A significant association between hospital performance for stroke care process and outcomes was found, supporting the use of broad, guideline-recommended performance metrics (including Get With The Guideline-Stroke) as a means of evaluating and helping improve hospital stroke care quality in China.
Abstract 121: Vascular Risk Factor Control in the Year After Ischemic Stroke Versus Myocardial Infarction
Authors: Bravata Dawn M , Brosch Jared , Sico Jason , Baye Fitsum , Myers Laura , Roumie Christianne , Cheng Eric , Miech Edward J , Williams Linda S , Arling Greg
Published: July 2021

Background:
The Veterans Health Administration has multiple quality improvement activities directed at improving vascular risk factor control. We sought to examine facility quality of blood pressure (BP) control (<140/90 mm Hg), lipid control (LDL-cholesterol <100 mg/dL) and glycemic control (HbA1c <9%) in the one-year after hospitalization for ischemic stroke or acute myocardial infarction (AMI).

Methods:
We assembled a retrospective cohort of patients hospitalized with stroke or AMI (fiscal year 2011). Facilities were included if they admitted ≥25 stroke patients and ≥25 AMI patients. A facility-level consolidated measure of vascular risk factor control was calculated for the 3 processes of care (number of passes divided by number of opportunities).

Results:
A total of 2432 patients had a new stroke and 4873 had a new primary AMI (at 75 facilities). Stroke patients had worse vascular risk factor control than AMI patients (mean facility rate on consolidated measure: stroke, 70% [95%CI 0.68-0.72] vs AMI, 77% [0.75-0.78]). The greatest disparity between stroke and AMI patients was in hypertension control: at 87% of hospitals, fewer stroke patients achieved BP control than AMI patients (mean facility pass rate: stroke, 41% vs AMI, 52%; p<0.0001). Overall there were no statistical differences for stroke versus AMI patients in facility-level hyperlipidemia control (71% vs 73%, p=0.33) and glycemic control (79% versus 82%, p=0.24). AMI patients had more outpatient visits than stroke patients in the year after discharge [AMI: mean 7.9 visits (standard deviation 6.1)]; stroke: mean 6.0 visits (standard deviation 4.5; p<0.0001].); the primary difference in outpatient utilization was additional cardiology visits for AMI patients (2.5 visits with cardiology per AMI patient vs 0.4 visits per stroke patient; p<0.001).

Conclusions:
These results demonstrated clinically substantial disparities in hypertension control among patients with stroke vs patients with AMI. It may be that cardiologists provided risk factor management to AMI patients that stroke patients did not receive. The etiology of these observed differences merits additional investigation.
Abstract 136: Prediction of Postoperative Hyperperfusion by Intraoperative Assessment of Indocyanine Green Videoangiography in Moyamoya Disease
Authors: Uchino Haruto , Ito Masaki , Kazumata Ken , Nakayama Naoki , Kuroda Satoshi , Houkin Kiyohiro
Published: July 2021

Background:
Postoperative hyperperfusion is a potential complication of the direct bypass procedure for moyamoya disease (MMD). However, no reliable modality is available yet for the prediction of postoperative hyperperfusion during surgery for MMD. This study aimed to investigate whether semiquantitative analysis of indocyanine green (ICG) videoangiography could contribute to the prediction of postoperative hyperperfusion in MMD.

Methods:
This study included 12 hemispheres from 10 patients who underwent surgical revascularization for MMD. Intraoperative ICG videoangiography was performed before and after a direct bypass procedure. The ICG intensity-time curves were semiquantitatively analyzed to evaluate cortical perfusion by calculating the blood flow index (BFI). Using single-photon emission computed tomography (SPECT), postoperative cerebral blood flow measurements were performed thrice: immediately and 2 and 7 days after surgery.

Results:
BFI significantly increased from 21.3 ± 10.5 to 38.4 ± 20.0 after bypass procedures in all the hemispheres (p < 0.01). The ratio of BFI before and after the bypass procedure was 2.4 ± 2.0, ranging from 0.5 to 8.0. Postoperative hyperperfusion was observed in 9 of the 12 operated hemispheres within 7 days after surgery. Of these, 3 hemispheres developed hyperperfusion immediately after surgery. In the adult cases, the increase in the ratio of BFI after bypass was significantly greater in those who developed hyperperfusion immediately after surgery than in those who did not (6.5 ± 0.5 vs. 1.8 ± 2.1, p < 0.01). In contrast, no significant increase in BFI was observed in the pediatric MMD patients who experienced immediate hyperperfusion. No correlation between the changes in BFI and the occurrence of delayed hyperperfusion was observed.

Conclusions:
Our results suggest that semiquantitative analysis of BFI by intraoperative ICG videoangiography is useful in evaluating changes in cortical perfusion after bypass procedures for MMD and can predict the occurrence of early-onset hyperperfusion in MMD patients after direct bypass.
Abstract 14: Use of an Insertable Cardiac Monitor to Detect Atrial Fibrillation is Cost Effective in Patients with Cryptogenic Stroke
Authors: Diamantopoulos Alex , Sawyer Laura , Sungher Dilpreet , Lip Gregory , Witte Klaus , Reynolds Mathew R , Fauchier Laurent , Thijs Vincent , Brown Ben , Quiroz Maria E , Diener Hans-Christoph
Published: July 2021

Introduction:
The cause of ischemic stroke remains uncertain (cryptogenic stroke) in 20-40% of cases despite conventional diagnostic tests. Documentation of atrial fibrillation (AF) is required to initiate anticoagulant therapy to reduce recurrent stroke risk, however, the paroxysmal and asymptomatic nature of AF means it is often not detected with traditional monitoring techniques. We assessed the hypothesis that detecting AF via continuous long-term monitoring with an insertable cardiac monitor (ICM) is cost effective for preventing recurrent stroke in cryptogenic stroke patients, in comparison to Standard of Care (SoC).

Methods:
A randomized controlled trial reported a nine-fold increase in AF detection with an ICM (Reveal XT, Medtronic) compared to SoC over 3 years follow-up, after exclusion of patients with evidence of AF from initial tests. A lifetime Markov model was developed which uses trial data to estimate cost effectiveness of ICM from a U.K. NHS perspective. The CRYSTAL AF study provided AF detection rates, ICM implant complications, resource use and baseline quality of life. Safety and efficacy data for specific non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin were sourced from literature to estimate stroke and bleeding risks. Other quality of life and cost data were sourced mainly from the UK OXVASC study. All costs and benefits were discounted at 3.5% and scenario analyses (CHADS2 score) and probabilistic sensitivity analyses (PSA) were conducted.

Results:
ICM was associated with fewer recurrent strokes and increased Quality Adjusted Life Years (QALYs) compared to SoC. Stroke-related costs were reduced in the ICM arm, however, overall costs did remain higher than SoC. The incremental cost-effectiveness ratio (ICER) was below a £30,000 per QALY gained willingness-to-pay threshold. Sensitivity analysis indicated that the ICER increased in patients with lower CHADS2 scores, however, it remained below the threshold.

Conclusion:
AF detection with ICM increases linearly over its 3 year life, identifying AF in nine-fold more patients than SoC. ICM appears to be a cost-effective diagnostic tool for the prevention of recurrent stroke in patients with cryptogenic stroke in the UK and countries with similar healthcare systems.
Abstract 15: Preoperative Transdural Collaterals in Moyamoya
Authors: Akagbosu Cynthia , Storey Armide , Robertson Richard , Scott R. Michael , Smith Edward
Published: July 2021

Introduction:
The prevalence of angiographically evident pre-operative transdural collaterals to the brain in moyamoya is not well documented.

Hypothesis:
We hypothesized that presence of transdural collaterals would be associated with more advanced moyamoya disease at diagnosis, more frequent operative complications and better long-term angiographic results.

Methods:
Single institution case series reviewing all moyamoya patients with 6 vessel arteriograms treated surgically from 2005-2013.

Results:
204 patients (n=121 (59%) F / 83 (41%) M) were diagnosed with moyamoya at 9.5 years of age (range 0.4-35 years). Presentation included ischemia (84% stroke or TIA), headache (36%), incidental (7%), chorea (3%) and hemorrhage (1%).

Radiographically, 154 (75%) had bilateral disease for a total of 358 affected hemispheres, 152 (75%) had radiographic stroke and 190 (93%) had ivy sign on FLAIR MRI, indicating slow flow.

Of the 358 hemispheres, 324 were treated operatively.

On preoperative angiogram, 99 patients (49%) had transdural collaterals in 174 affected hemispheres (54%). Suzuki grades were higher in patients with collaterals (3.4 vs. 3.0, p=0.002). Of a total of 324 treated hemispheres, 84 (26%) had collaterals within the area of the surgical field.

Complications included 12 strokes (3.7% stroke rate per hemisphere), with 5 (42%) directly attributable to interruption of a transdural collateral.

In one-year postoperative arteriograms in 215 hemispheres, while not significant, Matsushima grades trended better in patients with preoperative collaterals, (1.6 vs. 1.8; A=1, B=2, C=3, p=0.09).

Conclusions:
In conclusion, transdural collaterals are present in nearly half of all moyamoya patients. They are more common in advanced disease, are associated with stroke as a perioperative complication and may suggest increased capacity to produce surgical collaterals postoperatively. These data support the utility of preoperative arteriograms.
Abstract 158: Temporal Trends in tPA Administration Among Very Elderly Hospitalized with Ischemic Stroke in the United States
Authors: Lin Michelle P , Cen Steven , Towfighi Amytis , Kim-Tenser May , Mack William J , Sanossian Nerses
Published: July 2021

Background:
Rates of tPA administration in very elderly (age≥80) have historically been lower than the general population, perhaps due to their under-representation in thrombolysis stroke trials. While the population of very elderly individuals is rapidly growing, nationwide trends in tPA administration and stroke outcomes in this group have not been well described.

Methods:
Data were obtained from all US states that contributed to the Nationwide Inpatient Sample. All patients (N=5,959,914) admitted to hospitals between 2000 and 2010 with a discharge diagnosis of ischemic stroke (ICD9 codes) were included. Primary analysis was the proportion of patients who received tPA administration stratified by age (18-64yo, 65-79yo, ≥80yo) temporally. Survey
-
weighted Poisson regression was used to estimate the standardized rate for each year and compare the trend for yearly change between age categories.

Result:
Hospitalizations for acute stroke in the US were roughly split 1/3 into each age category: 80 years of age or older (35%), between 65 to 79 years of age (37%), and 18 to 64 years of age (28%). tPA administration rate increased by year from 2000 to 2010 regardless of age. In 2000, tPA administration rate was 1.02%, 0.92%, 0.47% in patients aged 18-64, 65-79yo, ≥80 years of age, respectively. In 2010, tPA administration rate was 3.61%, 3.87%, 3.55%, respectively. The magnitude of change was the greatest in very elderly individuals age 80 or older with the rate of increase of 1.25 (1.25-1.26), compared to other age groups 1.15 (1.15-1.16) for age 18-64yo, and 1.17 (1.17-1.18) for age 65-79yo.

Conclusion:
Over the last decade, the rate of tPA administration for acute ischemic stroke in the United States have increased for every age group. The magnitude of increase was the greatest in very elderly individuals aged 80 or above. Given the rapidly ageing US population, avenues for improving safe and effective administration of tPA among very elderly with stroke need to be further explored.
Abstract 16: Lenticulostriate Collaterals Predict Angiographic Course in Unilateral Focal Cerebral Arteriopathy of Childhood
Authors: Elbers Jorina , Benseler Susanne M , Armstrong Derek , Steinberg Gary K , Yeom Kristen W
Published: July 2021

Introduction:
Focal cerebral arteriopathy (FCA) is a frequent cause of stroke in children and an important risk factor for stroke recurrence. The factors affecting progression of FCA remain undetermined.

Hypothesis:
We hypothesized that the presence of lenticulostriate (LS) collaterals at presentation can serve as a prognostic marker of progressive arteriopathy in children with unilateral FCA.

Methods:
Children aged 1-month to 18-years with FCA, defined as unilateral steno-occlusive disease at the carotid terminus, were retrospectively identified from two centers. Presence of collaterals was based on digital subtraction angiography (DSA) at baseline. The patients’ imaging (MR angiogram or DSA) dataset at baseline and last follow-up was reviewed by 2 blinded raters and their outcomes classified as improved, stable, or progressed based on location and degree of steno-occlusive disease. The presence or absence of LS collaterals at presentation and angiographic outcomes were compared using Fisher’s exact test.

Results:
Our study included 46 children; 24 males, with median age 8.2 years (range 2-17.4 years), of which 21 had LS collaterals at presentation (46%). Median follow-up periods were 12 months and 19 months for the collateral and non-collateral groups, respectively. Angiographic improvement occurred exclusively in the non-collateral group (48%) (p=0.0001). In the collateral group, progression occurred ipsilaterally in 29%, and contralaterally in 14%. In the non-collateral group, progression was only ipsilateral, occurring in 35%. Discordant progression, defined as progression and improvement across multiple vessels, only occurred in the non-collateral group (67%) (p=0.02). No patients in the non-collateral group developed LS collaterals.

Conclusion:
The presence of LS collaterals in FCA was associated with ipsilateral or contralateral progression, while their absence was associated with ipsilateral progression or improvement. We conclude that LS collaterals in FCA likely signify a chronic, progressive process recognized as Moyamoya disease. In the absence of collaterals, steno-occlusion may progress in a discordant fashion or improve, indicating a varied vascular response to injury or inflammation, and the capacity to heal.
Abstract 203: Use of Endovascular Therapy and Trends in Clinical Outcomes within the Nationwide Get With The Guidelines-Stroke Registry
Authors: Menon Bijoy K , Saver Jeffrey L , Goyal Mayank , Noguiera Raul , Prabhakaran Shyam , Liang Li , Xian Yang , Hernandez Adrian , Fonarow Greg C , Schwamm Lee , Smith Eric E
Published: July 2021

Purpose:
To determine hospital and patient level characteristics associated with use of endovascular therapy for acute ischemic stroke and to analyze trends in clinical outcome.

Methods:
Data were from Get With The Guidelines-Stroke hospitals from 4/1/2003 to 6/30/2013. We looked at secular trends in number of hospitals providing endovascular therapy, use of endovascular therapy in these hospitals, and clinical outcomes. We also analyzed hospital and patient characteristics associated with endovascular therapy utilization.

Results:
Of 1087 hospitals, 454 provided endovascular therapy to at least one patient in the study period. From 2003 to 2012, the proportion of hospitals providing endovascular therapy increased by 1.6%/year (from 12.9% to 28.9%), with a modest drop in 2013 to 23.4%. Use in these hospitals increased from 0.7% to 2% of all ischemic stroke patients (p<0.001) with a modest drop in 2013 to 1.9%. In multivariable analyses, patient outcomes after endovascular therapy improved over time, with reductions in in-hospital mortality (29.6% in 2004 to 16.2% in 2013; p=0.002); and from late 2010, reduction in symptomatic intracranial hemorrhage (ICH) (11% in 2010 to 5% in 2013; p<0.0001) and increased independent ambulation at discharge (24.5% in 2010 to 33% in 2013; p<0.0001) and discharge home (17.7% in 2010 to 26.1% in 2013; p<0.0001) (Attached figure). Hospital characteristics associated with endovascular therapy use included large size, teaching status and urban location while patient characteristics included younger age, EMS transport, absence of prior stroke and white race.

Conclusion:
Use of endovascular therapy increased modestly in this national registry from 2003 to 2012 and decreased in 2013. Clinical outcomes improved notably from 2010 to 2013, coincident with the introduction of newer thrombectomy devices.
Abstract 215: Efficacy and Safety of Novel Oral Anticoagulants (NOACs) in Asian population with Non-Valvular Atrial Fibrillation (NVAF) - A Meta-Analysis
Authors: Fukuda Mayumi , Singer Daniel E , Bain Paul A , Sato Shoichiro , Kobayashi Daiki , Doi Yohei , Toyoda Kazunori
Published: July 2021

Background and purpose:
Asians have higher risk of intracranial hemorrhage (ICH) compared to non-Asians. Although recent clinical trials have shown non-vitamin K antagonist oral anticoagulants (NOACs) were favorable in preventing ICH as well as thrombotic events among patients with non-valvular atrial fibrillation (NVAF), it is unclear whether the efficacy and safety of NOACs are consistent among Asians. The purpose of this study is to assess the efficacy and safety of NOACs in Asians with NVAF.

Methods:
PubMed, Embase, Cochrane Central, Web of Science, the Western Pacific Index Medicus, Clinicaltrials.Gov and supplemented with conference abstracts were searched up to June 2014. Phase III randomized control trials that reported efficacy and safety of NOACs vs. warfarin in Asians and non-Asians with NVAF were identified. Each study was reviewed by two reviewers and differences were resolved by consensus. The end points analyzed were all stroke or systemic embolism, ischemic and hemorrhagic stroke, major or clinically relevant non major bleeding events (CRNM), and ICH. The hazard ratio (HR) with 95% confidence interval (CI) of each endpoint in NOACs compared to warfarin was extracted separately among Asians and non-Asians. Random-effects models were used to calculate pooled HR and 95% CI.

Results:
5 eligible studies were identified. Total of 8928 Asians and 64023 non-Asians were included. All stroke or systemic embolism were significantly reduced with NOACs in Asians (HR: 0.72 [95% CI: 0.59-0.88], p=0.002) but not in non-Asians (HR: 0.82 [0.66-1.01], p=0.097). The risk of ischemic stroke was not decreased in Asians (HR: 0.88 [0.64-1.21], p=0.43) or non-Asians (HR: 0.98 [0.80-1.12], p=0.73), whereas the risk of hemorrhagic stroke was significantly decreased in both groups (HR: 0.28 [0.17-0.47], p<0.001 for Asians, HR: 0.37 [0.24-0.55], p<0.001, respectively). The risk of major bleeding or CRNM was significantly reduced in Asians (HR: 0.68 [0.56-0.83], p<0.001) but not in non-Asians (HR: 0.78 [0.60-1.0], p=0.21). The risk of ICH was significantly decreased in both groups (HR: 0.30 [0.21-0.42], p<0.001, HR: 0.41 [0.34-0.48], p<0.001, respectively).

Conclusions:
The efficacy and safety of NOACs in Asians with NVAF is consistent with the overall results.
Abstract 45: Effect Of Atrial Fibrillation On Brain Atrophy And Cognitive Deficits In Persons Aged ≥65 Years: Analysis Of Cardiovascular Health Study
Authors: Chughtai Morad , Bezzina Cara , Zeb Hashim , Malik Ahmed A , Qureshi Adnan I
Published: July 2021

Background:
We tested the hypothesis that surrogate markers of brain degeneration such as atrophy are more prevalent in persons with atrial fibrillation who are at risk for cognitive deficits.

Methods:
We analyzed the data from the 2,962 women and 2,239 men and added minority cohort of 256 men and 431 women (all aged ≥65 years) enrolled in the Cardiovascular Health Study. Examination components have included medical history questionnaires, measurement of ankle-brachial index, abdominal and carotid ultrasound studies, ambulatory electrocardiograms, and cerebral magnetic resonance imaging (MRI) over the past decade. Atrophy was graded using a nine point scale (1 through 9) based on severity of atrophy. Logistic regression analysis was performed to determine the relationship between atrial fibrillation and prominent atrophy after adjusting for potential confounders.

Results:
Atrial fibrillation was present in 125 (3.4%) of the 2775 participants who received an MRI at baseline evaluation. The mean mini mental status score (±SD) was similar among participants with atrial fibrillation compared to those without atrial fibrillation (27.8 ±2.3 versus 27.6 ±2.7, p=0.4). The proportion of participants with prominent sulcal atrophy (score of 4 or greater) was non significantly higher among patients with atrial fibrillation (61 of 125 and 1097 of 2650, p=0.1). The proportion of participants with prominent ventricular atrophy (score of 4 or greater) was non significantly higher among patients with atrial fibrillation (69 of 126 and 1287 of 2651, p=0.2). The proportion of participants with previous cortical infarction (46 of 125 and 765 of 2650, p=0.06) and marked perivascular space expansion (5 of 125 and 27 of 2650, p=0.006) on MRI was significantly higher among patients with atrial fibrillation and sulcal atrophy. After adjusting for age, gender, and previous infarction, participants with atrial fibrillation did not have a higher risk of prominent atrophy (odds ratio 0.7, 95% confidence interval 0.5 -0.9, p=0.005).

Conclusions:
We observed that brain atrophy was more prevalent among persons with atrial fibrillation but due to the age differences and the higher occurrence of previous infarctions.
Abstract 59: In-hospital Outcomes of Thrombolysis in Dementia Patients with Ischemic Strokes
Authors: Nasr Deena , Rabinstein Alejandro , McDonald Jennifer
Published: July 2021

Background and Purpose:
Although IV tissue plasminogen activator (tPA) is standard care for acute ischemic strokes (AIS), its administration continues to be a topic of controversy among patients with dementia. This study compared in-hospital outcomes for dementia versus non-dementia patients treated with IV tPA for acute ischemic strokes.

Materials and Methods:
Using the Nationwide Inpatient Sample (NIS) from 2001-2010, patients with the primary diagnosis of ischemic stroke were identified. We studied outcomes of IV-tPA treatment for acute ischemic stroke in patients with dementia versus a non-dementia control group. Using a 1:2 matched propensity score analysis we controlled for demographic factors, cardiovascular comorbidities and Charlson comorbidity index between groups. Outcomes studied included in-hospital mortality, hospital discharge status and intracranial hemorrhage (ICH).

Results:
A total of 24,904 patients with acute ischemic strokes who underwent IV tPA therapy for AIS were included in this study. 659 of which had a diagnosis of dementia. After 1:2 matching based off of age, gender, cardiovascular risk factors and Charlson comorbidity index there were a total of 657 patients in the dementia group and 1314 patients in the non-dementia group. Patient outcomes after propensity core analysis showed no difference with in-hospital mortality in the dementia group vs. control (13% vs 14%, p=0.67), discharge to long-term care facilities (63% vs 59%, p=0.08) and ICH (7.9% vs. 9.1%, p=0.86).

Conclusions:
There was no statistically significant difference in in-hospital mortality, discharge status or ICH rates in patients with AIS and dementia who received IV tPA compared to those without dementia. These results suggest that dementia is not a predictor of poor in-hospital outcome following IV tPA administration for AIS. Further longitudinal studies are needed to determine if IV tPA therapy would improve long-term outcomes for dementia patients with AIS.
Abstract 63: Three-month Outcomes in Japanese Stroke /TIA Patients With Non-valvular Atrial Fibrillation After Initiating Oral Anticoagulants: The SAMURAI-NVAF Study
Authors: Arihiro Shoji , Todo Kenichi , Koga Masatoshi , Yamagami Hiroshi , Terasaki Tadashi , Kimura Kazumi , Shiokawa Yoshiaki , Kamiyama Kenji , Takizawa Shunya , Okada Yasushi , Hasegawa Yasuhiro , Okuda Satoshi , Mochizuki Hiroshi , Ito Yasuhiro , Nakashima Takahiro , Kameda Tomoaki , Nagakane Yoshinari , Takamatsu Kazuhiro , Nishiyama Kazutoshi , Furui Eisuke , Kario Kazuomi , Honma Kazunari , Takasugi Junji , Tokunaga Keisuke , Toyoda Kazunori
Published: July 2021

Backgound and Purpose:
Recently, three non-vitamin K antagonist oral anticoagulants (NOACs) became available for patients with nonvalvular atrial fibrillation (NVAF) in Japan. We aimed to determine 3-month outcomes in ischemic stroke/TIA patients receiving NOACs or warfarin from a multicenter prospective registry (SAMURAI-NVAF registry, NCT01581502).

Methods:
Among 1,191 acute ischemic stroke /TIA patients enrolled between September 2011 and March 2014, we studied 916 patients (389 women, 77±10 y) who took oral anticoagulants (OACs) after index stroke and completed 3-month follow-up survey. Primary outcome measures were ischemic events, including recurrent stroke/TIA and thromboembolism, and major bleedings events, such as fatal bleeding and/or symptomatic bleeding in a critical area or organ according to the International Society on Thrombosis and Haemostasis statement. We assessed the incidence and clinical factors associated with primary outcomes within 90 days after initiating OACs.

Results:
NOACs were given for 370 patients (126 women, 74±9 y; dabigatran 168, rivaroxaban 183 and apixaban 19) and warfarin for 546 (263 women, 79±10 y). NOAC users had lower scores of CHADS2 (median 3 in NOAC, 4 in warfarin, p<0.001) and HAS-BLED (3, 3, p<0.001) than warfarin users. Ischemic events occurred in 14 NOAC users (3.8%; 2 women, 76±6 y, including 8 lower dose users between two approved dose for each NOAC) and 25 warfarin users (4.6%; 13 women, 81±9 y). Of these, 13 NOAC users (3.5%) and 16 warfarin users (2.9%) developed ischemic stroke/TIA. Among NOAC users, patients with ischemic events had lower body weights (53±11 vs 60±11kg, p= 0.017), more frequently had congestive heart failure (36 vs 10%, p = 0.003) and intracardiac thrombus (27 vs 4%, p < 0.001) than those without. Major bleeding events occurred in 5 NOAC users (1.4%, all using lower dose), and 14 warfarin users (2.6%). Of these, one NOAC user (0.3%) and 4 warfarin users (0.7%) developed intracranial hemorrhage.

Conclusion:
The 3-month incidence of ischemic events in stroke/TIA patients with NVAF was approximately 4% in both NOAC and warfarin users. Intracranial hemorrhage was relatively infrequent in NOAC users.
Abstract 71: Endothelium-specific Deficiency of PPARδ Selectively Decreases Level of sAPPα in Hippocampus
Authors: He Tongrong , Lu Tong , Santhanam Anantha V , Katusic Zvonimir S
Published: July 2021

We tested the hypothesis that endothelial PPARδ plays an important role in the protection of neurovascular unit. Cerebral microvessels were isolated from mice with endothelium-specific deficiency of PPARδ (ePPARδ-/-) and littermate wild type (WT) mice. After ex vivo incubation of cerebral microvessels for 24 h, supernatant was collected and levels of soluble amyloid precursor protein α [sAPPα, a product of non-amyloidogenic processing of amyloid precursor protein (APP)] were measured using an ELISA kit. The production of sAPPα in cerebral microvessels of ePPARδ-/- mice was reduced by 54%, as compared to WT mice (n=6-7, P<0.05). Western blot analysis demonstrated that microvascular expression of ADAM10 was reduced in ePPARδ-/- mice (80%) (n=18, P<0.05), while ADAM17 protein level was increased in by 132% (n=4, P<0.05), as compared to WT mice. Protein expressions of APP, ADAM9, and BACE1 were not significantly different between cerebral microvessels derived from ePPARδ-/- mice and WT mice. Real-time RT-PCR demonstrated that in brain microvessels of ePPARδ-/- mice mRNA levels of ADAM10 were also decreased by 56% (n=5, P<0.05). Furthermore, Western blot analysis of the brain regions showed that sAPPα content was selectively reduced in hippocampus of ePPARδ-/- mice by 80% (n=11, P<0.05). This was associated with significantly reduced expression of ADAM10 in the hippocampus (n=11, P<0.05). In contrast, protein levels of ADAM10, and sAPPα were not altered in cortex and cerebellum of ePPARδ-/- mice. In addition, we did not detect any changes in Aβ40 and Aβ42 levels (measured using ELISA assay) in all three examined brain regions. Since sAPPα is a potent neurotrophic and neuro-protective molecule, our results suggest that loss of endothelial PPARδ may selectively increase vulnerability of hippocampus. This mechanism may contribute to susceptibility of hippocampus to injury during initiation and progression of neuro-degenerative diseases.
Abstract 74: Improvement in Cerebral Hemodynamic Parameters and Outcome after Superficial Temporal Artery- Middle Cerebral Artery Bypass in Patients with Severe Steno-occlusive Disease of Intracranial Carotid and Middle Cerebral Artery
Authors: Yeo Leonard , Paliwas Prakash , Ahmad Aftab , Sindha Arvind K , Teoh Hockluen , Wong Lily Y , Chong Vincent F , Seet Raymond C , Chan Bernard P , Yeo Tsengtsai , Chou Ning , Sharma Vijay K
Published: July 2021

Background and Objective:
Older and the recent extracranial-intracranial (EC/IC) bypass trials for symptomatic carotid occlusion failed to demonstrate reduction in stroke recurrence. However, role of superficial temporal artery-middle cerebral artery (STA-MCA) bypass in patients with symptomatic intracranial steno-occlusive disease has been evaluated scarcely. We evaluated serial changes in various cerebral hemodynamic parameters in patients with severe steno-occlusive disease of intracranial internal carotid (ICA) or middle cerebral artery (MCA) and impaired cerebral vasodilatory reserve (CVR), treated with STA-MCA bypass surgery or medical treatment.

Methods:
Patients with severe steno-occlusive disease of intracranial ICA or MCA underwent transcranial Doppler (TCD) ultrasonography and CVR assessment using breath-holding index (BHI). Patients with impaired BHI (<0.69) were further evaluated with acetazolamide-challenged hexamethylpropyleneamine-oxime single-photon emission computed tomography (HMPAO-SPECT). STA-MCA bypass surgery was offered to patients with impaired CVR on SPECT. All patients underwent TCD and SPECT at 4±1 months and followed-up for cerebral ischemic events.

Results:
A total of 112patients (73males, mean age 56yrs; range 23-78yrs) were included. HMPAO-SPECT demonstrated impaired CVR in 77 (69%) patients. Of them, 46 underwent STA-MCA bypass while 31 received best medical treatment. TCD and acetazolamide-challenged HMPAO-SPECT repeated 4±1months showed significant improvement in STA-MCA bypass group. During follow-up (mean 34months; range 18-39months), only 6/46 (13%) patients in bypass group developed cerebral ischemic events as compared to 14/31 (45%) cases on medical therapy (absolute risk-reduction 32%, p=0.008).

Conclusion:
STA-MCA bypass surgery in carefully selected patients with symptomatic severe intracranial steno-occlusive disease results in significant improvement in hemodynamic parameters and reduction in stroke recurrence.
Abstract 76: Genetic Interference with PPARγ in Endothelium Accelerates Oxidative Stress, Inflammation, and Vascular Senescence With Aging
Authors: Li Ying , De Silva Travice M , Kinzenbaw Dale A , Sigmund Curt D , Faraci Frank M
Published: July 2021

Although aging is the greatest risk factor for vascular disease and stroke, very little is known regarding mechanisms that control vascular aging. Endothelial dysfunction - a critical element of carotid artery and cerebrovascular disease - progresses with age, contributing to increased risk for ischemic stroke and cognitive impairment. The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) exerts protective effects in the vasculature when pharmacologically activated. Because endothelial PPARγ may normally protect against vascular disease, we examined the hypothesis that genetic interference with PPARγ in endothelium would promote vascular aging. We studied carotid arteries from adult (11-12 mo) and old (24±1 mo) transgenic mice with endothelial specific expression of a dominant negative mutation in PPARγ driven by the vascular cadherin promoter (designated E-V290M), along with age-matched, non-transgenic (NT) littermates. Acetylcholine (an endothelium-dependent agonist) produced similar relaxation of arteries from adult NT and E-V290M mice as well as old NT mice. In contrast, responses to acetylcholine were reduced by greater than 50% in old E-V290M mice (P<0.01). Endothelial function in old E-V290M mice was not altered by an inhibitor of cyclooxygenase, but was restored to normal by a superoxide scavenger, or an inhibitor of NADPH oxidase, or inhibition of Rho kinase. Relaxation of arteries to nitroprusside, which acts directly on vascular muscle, was similar in all groups. Vascular expression of interleukin-6, a mediator of vascular disease, was increased 1.6-fold in old NT mice, but almost 9-fold in old E-V290M mice (P<0.05). Interestingly, expression of CDKN2A, a molecular marker of senescence, was increased 2.6-fold in old NT mice, but almost 6-fold in old E-V290M mice (P<0.05). These findings provide the first evidence that senescence and age-related vascular dysfunction is accelerated following cell-specific interference with endothelial PPARγ through mechanisms that appear to involve oxidative stress, inflammation, and Rho kinase. This critical role for endothelial PPARγ has implications for vascular pathophysiology as well as therapeutic approaches for age-induced large and small vessel disease.
Abstract 8: Delay In Consent Is a Common Reason For Delay In tPA Administration
Authors: Murphy Sheree , Colello Anna , Levine Steven R
Published: July 2021

Background:
Hospitals target the “golden hour”, tPA within 60 minutes of stroke patient arrival to speed delivery of the drug. However this target is missed in > 50% of cases. Reasons for delays may be addressable.

Objective:
Determine the type and frequency of delays in tPA treatment within New York State (NYS).

Methods:
Reasons for delay in IV tPA beyond 60 minutes of hospital arrival were collected in the Get With The Guidelines (GWTG)-Stroke Patient Management Tool for hospitals participating in the NYS Department of Health (NYS DOH) Stroke Center Designation program. Data were a reporting requirement for all 2012 patient discharges. Abstractors selected all reasons either explicitly documented or clearly apparent - delay from door to stroke diagnosis, to MD, to stroke team, to CT, to CT read, to lab results, IV tPA order to initiated, difficult IV access, patient/family consent, equipment-related, management of concomitant emergent/acute condition, change in patient clinical status/condition, and other. Aggregate data for all NYS hospitals were obtained. Chi squared was used to test differences (2-tailed).

Results:
From 41,709 records with 23,850 ischemic strokes enrolled in GWTG-Stroke from 120 hospitals in NYS during calendar year 2012, inpatient stroke cases were excluded (1,230) leaving 22,620 ischemic strokes. IV tPA was given to 1,991(8.8%). Delay in tPA occurred in 1,145 (58%) with reason for delay in 1,116 (97%). Patient/family consent was a factor in delay in 239 (21%). Other most frequently observed reasons being “other” in 369 (33%) and “management of concomitant emergent/acute condition” in 233 (21%). Females were more likely to experience delay due to patient/family consent compared with males (62% vs. 38%, p = 0.004). Weekend arrival was seen in 36% of consent delays (p = 0.001 from 27% expected).

Conclusions:
Our state-level data suggest that issues with consent are one of the most common reasons for delay in tPA. A potential gender issue is raised requiring further study. Delay on weekend vs. weekday suggests Stroke Centers review variations in stroke center processes that may be present on weekends. Training and tools to improve and shorten the consent process may reduce delays.
Abstract 81: Spatial Pattern and Ecologic Analysis of the Impact of Air Pollution on the Prevalence of Stroke, Coronary Heart Disease and Diabetes Mellitus, and Premature Death in the United States
Authors: Liu Longjian
Published: July 2021

We aimed to examine the associations of air pollutants and climate change with prevalence of stroke, coronary heart disease (CHD), diabetes (DM) and premature mortality. We used 2010-2013 daily monitoring air pollution data across 200 to 600 counties of 50 U.S. states, and health outcomes data from U.S. EPA and CDC. Six common air pollutant indicators were studied: particulate matters (PM2.5 and PM10), carbon monoxide (CO), nitrogen dioxide (NO), Ozone (O3), sulfur dioxide (SO2), and lead. Monthly, seasonally, and then a 4-yearly average pollutant level was estimated for each county. Air pollution index was weighted by population density. The results show that counties with higher levels of air pollutant indexes had significantly higher prevalence of stroke, CHD, DM and premature death rate (defined as subjects died before 75 years old). After adjustment for county-level socioeconomic status (median household income), these associations remained significant, except for a non-significant association of lead with CHD (0.11, p=0.18) and DM (0.16, p=0.052). Stratification analysis by quartiles of county-level yearly average temperature (F) showed that associations between air pollutants and prevalence of stroke was much stronger (assessed by correlation coefficients) for residents who lived in areas where it had yearly average temperature of 44.3 F (Q1) as compared to those who lived in areas with annual average temperature of 51.2 F (Q2). The corresponding correlation coefficients of PM2.5, PM10, CO, NO, O3, SO2, and lead with stroke rates were 0.55, 0.61, 0.61, 0.64, 0.62, 0.63, 0.49, respectively in residents living in the areas with Q1 temperate, and were 0.43, 0.36, 0.34, 0.32, 0.42, 0.31, and 0.45, respectively in those living in the areas with Q2 temperature. A stronger association between air index and stroke was also observed for residents who lived in an average temperature of 56.7 F (Q3), and 67.7 F (Q4). Similar associations were observed between air pollution and CHD, DM and premature death. In conclusion, using nationally representative datasets the present study provides new evidence of a positive and significant association of air pollution with stroke, CHD, DM and premature death, and these associations are modified by air temperatures.
Abstract 90: NIH Stroke Scale Assessment via iPad-based Mobile Telestroke During Ambulance Transport is Feasible - Pilot data from the Improving Treatment with Rapid Evaluation of Acute Stroke via Mobile Telemedecine (iTREAT) Study
Authors: Padrick Matthew M , Chapman Smith Sherita N , McMurry Timothy L , Mehndiratta Prachi , Chee Christina Y , Gunnell Brian S , Kimble Chance A , Cote Jack , Lippman Jason M , Burke Virginia M , Catell-Gordon David C , Rheuban Karen S , Solenski Nina J , Perina Debra G , Worrall Bradford B , Southerland Andrew M
Published: July 2021

Introduction:
The AHA-ASA Target:Stroke Program calls for innovative approaches to prehospital stroke care. We previously showed that mobile videoconferencing during ambulance transport is technically feasible in a rural EMS setting using an iPad-based telemedicine system. We now hypothesize that this mobile telestroke system is clinically feasible as measured by agreement of the NIH Stroke Scale (NIHSS) between face-to-face (FTF) and remote ambulance-based assessments (iTREAT).

Methods:
The iTREAT system comprises an Apple iPad® with retina display, high-speed 4G LTE modem, Cisco Jabber secure video conferencing application, mounting apparatus, and magnetic external antenna. We developed 4 unique stroke and 2 unique stroke-mimic scenarios to simulate prehospital stroke alerts. We recruited 3 standardized patients each assigned two scenarios, and randomly assigned each scenario to one of 6 major ambulance routes triaging to UVA Medical Center. To eliminate bias, we alternated the order of FTF and iTREAT evaluations. Statistical measures were inter- and intra-rater correlation coefficient for the NIHSS and audio/visual(AV) quality ratings on a 6-point scale (>4 indicating “good” or “excellent” connectivity).

Results:
For the 12 iTREAT and 10 FTF evaluations (two FTF missing data), intra-rater correlation of NIHSS scores was consistently >0.91 (mean=0.96). Inter-rater correlation for FTF evaluations was >0.89 (mean 0.96), and inter-rater correlation for iTREAT evaluations was >0.84 (mean=0.94). AV quality ratings during all iTREAT evaluations were deemed “good” or “excellent” (audio mean=5.3, median=5.5; video mean=4.67, median=4.5). Both NIHSS correlation and AV quality rating increased over the study period.

Conclusion:
In this pilot feasibility study, NIHSS scores obtained via ambulance using our iPad-based mobile telestroke system correlated well with in person assessments. These results support further research to determine feasibility and efficacy of this low-cost mobile telestroke system in prehospital stroke care.