bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W MP36: IV tPA Utilization and Outcomes in Asian Americans
Authors: Chong Ji Y , Navi Babak B , Kamel Hooman
Published: March 2022

Intro:
Studies have shown race/ethnic differences in IV tPA utilization and outcomes after acute ischemic stroke (IS). Most studies in the US have examined differences in Black, White, and Hispanic populations. We aimed to examine tPA utilization and outcomes in Asian Americans.

Methods:
We used administrative claims data on all discharges from nonfederal EDs and acute care hospitals in CA, FL, and NY from 2006 through 2011 (CA and NY) or 2012 (FL). We identified patients with a first-recorded hospitalization for IS using a validated algorithim and included discharge diagnosis of ICH or SAH if treated with tPA to capture cases of hemorrhagic transformation of an infarct. IV tPA was identified by
ICD-9-CM
procedure code 99.10. We used descriptive statistics to compare rates of IV tPA among different races. We used multiple logistic regression to assess the relationship between race and IV tPA use while adjusting for other demographic characteristics, vascular risk factors, and Elixhauser comorbid conditions. We assessed rates of ICH/SAH and inhospital mortality by race in patients treated with tPA.

Results:
Among 587,560 IS patients, 63.9% were White, 14.1% Black, 12.5% Hispanic, 4.5% Asian, 0.2% American Indian, and 2.8% other; 2.0% had missing data on race. Mean age was 72 years and 52% were women. Overall 4.8% received IV tPA. tPA use was 5.1% in Whites, 3.9% in Blacks, 3.9% in Hispanics, and 4.7% in Asians. After adjusting for age, gender, insurance status, and comorbidities, tPA use was less likely in non-White patients: Black OR 0.78 (95% CI 0.75-0.81), Hispanic OR 0.78 (95% CI 0.75-0.81), and Asian OR 0.94 (95% CI 0.88-0.995). ICH/SAH after tPA occurred in 16.9% of Asians compared with 11.3% of Whites, 12.2% of Blacks, and 13.6% of Hispanics. In multivariable analysis, Asian race was independently associated with ICH/SAH (OR 1.51; 95% CI 1.29-1.77). In-hospital mortality was also significantly higher in Asians (14.7%) compared to whites (12.6%); OR 1.19 (1.00-1.4).

Conclusion:
Asian patients less often receive tPA for IS. They also have higher rates of hemorrhage and in-hospital death after tPA. These findings are limited by lack of data on stroke severity, mechanisms, and treatment times. Further studies including these patient characteristics are warranted.
Abstract W MP42: Nationwide Database of Unruptured Cerebral Aneurysms Treated With Clipping or Coiling in Japan: The J-ASPECT Study
Authors: Nishimura Ataru , Kurogi Ryota , Nishimura Kunihiro , Kamitani Satoru , Kada Akiko , Sayama Tetsuro , Iihara Koji ,   The J-ASPECT Investigators
Published: March 2022

Background:
Evaluation of the overall clinical outcomes and health economics of stroke care is important for improving institutional quality of care. We performed a nationwide survey in Japan to analyze cases of unruptured cerebral aneurysms using the diagnostic procedure combination (DPC).

Methods and Results:
Certified neurosurgical training institutions in Japan provided data from the DPC database on patients hospitalized with neurosurgical diseases between April 1, 2012 and March 31, 2013. Patients hospitalized owing to unruptured cerebral aneurysms were identified from the DPC database based on the International Classification of Diseases (ICD)-10 diagnosis code (I671). We excluded patients with emergency admissions. We compared the mortality rates, modified Rankin Scale (mRS) scores, postoperative complications, and economic factors of patients who underwent clipping and coiling. With respect to postoperative complications, we evaluated the ratio of an event of complication (brain infarction, brain hemorrhage, cardiac infarction, and meningitis) and the number of complications (scored using a hospital-acquired condition). We used hierarchical logistic regression models to estimate the odds ratios (ORs) for in-hospital mortality and complications. The case volumes of clipping and coiling in each hospital were divided into quintiles, and trends were analyzed using the Cochran-Armitage trend test. We identified 5194 patients with unruptured cerebral aneurysms (3287 clipping, 1907 coiling). Patient characteristics, mortality rates, and mRS were similar between groups. Patients who underwent clipping had a significantly higher number of complications than patients who underwent coiling (β = -0.04; P = 0.03). Cases of brain infarction that had developed during hospitalization in both patients who had undergone clipping (OR = 0.28; P = 0.02) and patients who had undergone coiling (OR = 0.24; P = 0.047) were fewer in high-volume hospitals.

Conclusions:
Our results estimate the baseline national rates of outcomes and health and economic factors in patients with unruptured cerebral aneurysms that were treated with clipping or coiling. Our data may be useful for assessing institutional quality of care in comparison with national data.
Abstract W MP63: National Trends in Hospitalization Rates for Non-Hemorrhagic Cerebrovascular Disease in the United States among those 15 years and older: 1999 - 2010
Authors: Akinboro Oladimeji , Olorunfemi Odunayo , Pomerantz Daniel , Wasserman Sheldon , Basak Prasanta , Jesmajian Stephen
Published: March 2022

Background:
Non-hemorrhagic cerebrovascular disease (NH-CVD) is one of the leading causes of hospitalization in the United States (US). We describe the trends in NH-CVD hospitalizations in the US over a twelve-year period.

Methods:
We abstracted and analyzed data for NH-CVD hospitalizations, from 1999 to 2010, from the National Hospital Discharge Survey - a national probability sample of hospitalizations at US non-federal short-stay hospitals. NH-CVD hospitalizations were defined as hospitalizations whose principal diagnoses were coded using the International Classification of Diseases, 9th Revision, Clinical Modification codes 433-438. NH-CVD hospitalization rates were calculated for those 15 years and older, as well as among demographic sub-groups defined by age, race, gender, and geographical region. A multivariate logistic regression was modeled, with NH-CVD hospitalization as the outcome and time period as the main predictor, while controlling for age, gender, race, region, and comorbidities (diabetes, hypertension, atrial fibrillation, and dyslipidemia). We applied survey weights correcting for the sample design and non-response, in obtaining the population-based rates, odds ratio (OR), and confidence intervals (CI).

Results:
There were 9.8 million NH-CVD hospitalizations among those 15 years and older, from 1999 to 2010. NH-CVD hospitalization rates decreased by 26% from 39 per 10,000 (95% CI: 38, 41) in 1999, to 29 per 10,000 (95% CI: 28, 31) in 2007, and then increased by 24% to 36 per 10,000 (95% CI: 34, 38) in 2010. A similar pattern, with nadirs in 2007, was generally seen across all demographic sub-groups. On multivariate analysis, relative to the 1999-2001 triennium, the lowest odds of NH-CVD hospitalization were seen during 2005-2007 (OR 0.79; 95% CI: 0.76, 0.83).

Conclusion:
NH-CVD hospitalization rates in the US are increasing after an initial downward trend. Factors driving this trend are unclear, and it remains to be seen if it will be sustained. The current trend has great implications for healthcare resource utilization in a system already burdened by an aging population. This trend requires monitoring and warrants further research to identify its contributing causes.
Abstract W MP88: Worsening Of Stroke Outcome With Age Is Associated With Increased Intestinal Permeability And Peripheral Inflammation
Authors: Crapser Joshua , Ritzel Rodney , Doran Sarah , Koellhoffer Edward , Patel Anita , Friedler Brett , Verma Rajkumar , McCullough Louise
Published: March 2022

Introduction:
Aging remains the biggest risk factor for ischemic stroke. Initial observations into the role of aging on stroke outcome revealed that while aged mice had significantly smaller infarcts compared to young mice, they had greater long-term deficits in behavioral recovery. This study aimed to elucidate the role of systemic factors, such as intestinal stress, underlying the poor outcomes of aging mice after stroke.

Methods:
Young (8-12 wks) and aged (18-20 mos) wildtype mice were subjected to 90min of right middle cerebral artery occlusion (MCAO) followed by reperfusion. Intestinal permeability was measured with 4kDa FITC-dextran gavage. Mesenteric lymph node (MLNs) homogenates were plated on blood agar to measure bacterial growth. Bacterial endotoxin was measured using a LAL assay. Flow cytometry was used to assess immune cells. Plasma IL-6 was measured by ELISA.

Results:
Baseline gut permeability increased with age as evidenced by increased FITC-dextran extravasation across the intestinal lumina. Bacterial burden in MLNs and serum bacterial endotoxin levels were also elevated with age (p<0.05). These deficits were severely exaggerated by MCAO. A 200-fold increase was observed in the number of colony forming units in the MLNs of aged stroked mice compared to young (p<0.001). MHC II expression was enhanced on dendritic cells in aged MLNs and CD69 expression increased on circulating T-cells (p<0.05). Activated T-cells comprised the majority of infiltrating leukocytes in the ischemic hemisphere at 7 days post-stroke. This delayed recruitment of T-cells was associated with a 50% greater mortality of aged mice compared to young by 7 days. Plasma IL-6, a marker for sepsis, increased similarly at 6hr after MCAO in young and aged mice, but remained elevated in aged mice at 72hrs (p<0.05). Aged mice had lower body temperatures at 72hrs post-stroke (p<0.01).

Conclusion:
Our data suggest that the high mortality in aged mice after stroke is secondary to exacerbation of intestinal permeability, increased bacterial translocation, and subsequent induction of sepsis. This data points to gut-targeted interventions as a means to reduce the severity of peripheral inflammation and improve prognosis in aged stroke victims.
Abstract W P1: Reducing CT-To-Groin puncture Time for Endovascular Treatment of Acute ischemic Stroke: A High Volume Comprehensive Stroke Center Experience
Authors: Sapkota Biggya L , Sirelkhatim Abdelazim , Pitiyanuvath Nataria , Dellinger Caryl , Devlin Thomas G ,   Erlanger Southeast Regional Stroke Cntr
Published: March 2022

BACKGROUND:
One of the key variables that predict a good clinical outcome after endovascular stroke treatment is expeditious reperfusion. We describe a single center experience of process improvement to develop a streamlined Acute Stroke protocol in reducing CT-to-Groin Puncture (CTGP) time for endovascular stroke treatment (EVP) at Erlanger Medical Center.

MATERIAL AND METHODS:
All consecutive ischemic stroke patients who received EVP were retrospectively and prospectively registered in the stroke registry. A series of interventions to reduce treatment delays were implemented every year starting in 2012.Starting April 2013 provision for 24/7 in-house attending stroke neurologist presence was initiated. In-hospital delays were analyzed as annual mean/median CTGP time in minutes.

RESULTS:
A total of 176 patients were treated EVP between January 2011 to July 2014. The CTGP was reduced annually, from mean 275minutes (median118) in 2011, to 124 minutes (median104) in 2012, to 105 minutes (median99) in 2013 and 78minutes (median69) in 2014 (a 71% decrease in mean from 2011).

There was a significant difference in the CTGP time before and after the initiation of 24/7 in-house attending Stroke neurologist presence. The in-hospital mortality, LOS (length of stay) and sICH (symptomatic ICH) were not adversely affected.

Conclusion:
With multiple institution specific interventions, it is possible to improve the treatment times for endovascular stroke treatment even at a high volume non-academic center. The 24/7 in-house stroke neurologist’s presence is feasible and can be justified by expeditious patient selection for endovascular stroke treatment.

The next step will be to show the impact in improving clinical outcome after the successful reperfusion.
Abstract W P116: Cerebrovascular and Alzheimer’s Pathologies Combined in Mouse Models of Mixed Dementia Alter the Progression of Memory Impairment and Disease
Authors: Brothers Holly , Phillips Oliver W , Latta Clare H , Sudduth Tiffany L , Braun Kaitlyn , Wilcock Donna M
Published: March 2022

Dementia is most often attributed to Alzheimer’s disease (~70%) or vascular dementia (~17%), yet 20-50% of dementia cases share aspects of both. Better understanding of dementias within this spectrum can improve diagnosis, inform interpretation of clinical data confounded by co-morbidity, and direct therapeutic approaches. We hypothesized that combined pathologies alter the time-course of memory impairment and the expression of primary disease pathology. We compared and combined aspects of cerebrovascular disease (chronic cerebral hypoperfusion) and Alzheimer’s disease (transgene-driven tau or amyloid pathology). We induced chronic cerebral hypoperfusion by wrapping each common carotid artery with a microcoil that remains in situ and reduces cerebral blood flow to approximately 80%; a procedure called bilateral carotid artery stenosis (BCAS). To create conditions of mixed dementia, we performed BCAS in two transgenic models of Alzheimer’s pathology; the rTg4510 which overexpresses mutant human tau, and APP/PS1 that develops ß-amyloid pathology. Transgenic mice and their wildtype littermates received BCAS or sham surgeries near the onset of pathology survived 1 or 6 months, or during advanced pathology and survived 1 month. This generated 12 experimental groups (n of 4-11 each). We evaluated spatial memory impairment, neuroimmune phenotype, white matter integrity, tau pathology and ß-amyloid pathology. The progression of memory impairment and disease pathology is altered in the mixed dementia models, and these changes are relative to the age of onset and duration of hypoperfusion. For example, hypoperfusion has a larger impact on spatial memory impairment in aged APP/PS1 mice. Additionally, BCAS reduced the expression of CD86, an immune marker associated with a de-activated immune state, only in rTg4510 mice. These findings highlight changes in the time-course of cognitive impairment and pathology that might be expected in the substantial clinical population with co-morbid vascular and Alzheimer’s dementias.
Abstract W P12: Baseline Predictors of the Malignant Collateral Profile in IMS III
Authors: Liebeskind David S , Jovin Tudor G , Menon Bijoy K , Nogueira Raul G , Zaidat Osama O , Scalzo Fabien , Hill Michael D , Demchuk Andrew M , Carrozzella Janice , von Kummer Rüdiger , Khatri Pooja , Goyal Mayank , Al Ali Firas , Yan Bernard , Foster Lydia D , Yeatts Sharon D , Palesch Yuko Y , Broderick Joseph P , Tomsick Thomas A , Yoo Albert J ,   for the IMS III Investigators
Published: March 2022

Background:
Collateral circulation has repeatedly been cited as a decisive factor in successful angiographic and clinical outcomes after endovascular therapy, offering rational selection criteria. Identifying patients with a malignant collateral profile, portending poor outcome, would greatly enhance decision-making in acute stroke. We analyzed the IMS III dataset to delineate baseline predictors of poor angiographic collaterals.

Methods:
Collateral grade was prospectively evaluated by the angiography core lab in IMS III. Poor collaterals or a malignant collateral profile was defined as ASITN grade 0-1.

Baseline clinical, laboratory and non-contrast CT variables were evaluated in univariate and multivariable logistic regression as predictors of the malignant collateral profile.

Results:
278 patients (mean age 65.3±12.6 years, 54% women, median NIHSS 17 (IQR 13-20) had collateral grading assessed at angiography. Malignant collaterals (ASITN 0-1) were noted in 77/278 (28%). Univariate analyses revealed that only history of HTN (88.3 vs. 71.0%, p=0.004), CHF (17.6 vs.8.0%, p=0.040), admission DBP (89±24 vs. 81±17 (mm Hg, mean±SD), p=0.002), NIHSS>19 (40.3 vs. 28.4%, p=0.080), distal arterial occlusion location (p=0.002) and ASPECTS 0-4 (24.7 vs. 9.4%, p=0.002) were associated with malignant collaterals. Time from stroke onset to angiography was unrelated to collateral grade. Predictors in multivariable analyses included ASPECTS 0-4 (OR 3.72, 95%CI (1.60-8.66), p=0.002), HTN (OR 2.33, 95%CI (1.01-5.38), p=0.047), NIHSS>19 (OR 2.26, 95%CI (1.16-4.40), p=0.017), distal arterial occlusion (OR 2.08, 95%CI (1.43-3.04), p<0.001) and higher admission DBP (OR 1.02 per mm Hg, 95%CI (1.00-1.03), p=0.035). When ASPECTS 5-10, only NIHSS>19 (OR 2.81, 95%CI (1.35-5.86), p=0.006) and distal arterial occlusion (OR 2.58, 95%CI (1.70-3.92), p<0.001) predicted malignant collaterals.

Conclusions:
Elevated diastolic blood pressure, history of hypertension, NIHSS>19, lower ASPECTS and distal arterial occlusion are strong predictors of the malignant collateral profile. Future studies should validate and implement a concomitant risk score for triage of acute stroke patients.
Abstract W P131: Efficacy of Self-exercise on General Wards to Improve Activities of Daily Living: A Propensity Score Approach
Authors: Shiraishi Nariaki , Kuzuya Masafumi , Suzuki Yusuke , Jeong Seungwon , Sugiyama Motoya , Matsumoto Daisuke , Kondo Katsunori
Published: March 2022

Objective:
This study aimed to determine whether self-exercise (SE) correlates with an improvement in activities of daily living during hospitalization.

Methods:
The subjects were 1490 patients on general ward in 7centres. Items surveyed were age, sex, stroke type, length of stay, post-onset day of admission, motor functional independence measure (mFIM) and cognitive FIM(cFIM) at admission and at discharge, modified Rankin Scale (mRS) score before onset and at admission, Glasgow Coma Scale score at admission, presence/absence of SE, at least a 30% SE implementation rate(30%SE), and the presence/absence of hospital ward staff training(ST). In addition, the difference between mFIM at admission and at discharge (mFIM gain) was calculated. For analysis, a correlation between m FIM gain and the presence/absence of SE implementation was examined. SE implementation probability was subjected to stratification analysis using the propensity score (PS) and adjusted for confounding factors.

Results:
A significant difference in all items was noted based on the presence/absence of SE implementation. Among these, mFIM at discharge, cFIM at discharge, mFIM gain, and general wards having at least a 30% SE had a moderate to strong effect (0.53, 0.47, 0.49, and 0.44). PS was calculated for cFIM at admission, 30% SE , sex, age, mRS score at onset, and the presence/absence of ST .Stratification analysis revealed that the common odds ratio according to the Mantel-Haenszel test was 2.1, and therefore the probability for mFIM gain to be at least 22 points as a result of SE implementation was at least 2.1 times.

Conclusion:
This study used data from multicentres and therefore has excellent external validity. This study also determined the effect of SE implementation using the PS. Furthermore, the results suggest that SE implementation contributes to improvement in activities of daily living.
Abstract W P144: Depressive Symptoms and Risk of Stroke in African Americans: Findings from the Jackson Heart Study
Authors: O'Brien Emily C , Greiner Melissa A , Shahar Eyal , Hardy N. Chantelle , Sims Mario , Wang Wei , Hernandez Adrian F , Curtis Lesley H
Published: March 2022

Background:
Depression is a risk factor for stroke, yet most studies of this association have been conducted in white populations. We investigated the association between depressive symptoms and long-term stroke risk in a community-based cohort of African Americans.

Methods:
We used data from the Jackson Heart Study to investigate the association of depressive symptoms at baseline (between 2000 and 2004) with incident stroke risk over 9 years of follow-up. We classified depressive symptoms using the Centers for Epidemiologic Studies Depression (CES-D) scale. We used Kaplan-Meier estimates and Cox proportional hazards models to assess stroke risk using 3 exposure variables: any depressive symptoms (CES-D score ≥ 16); minor (score 16 to less than 21) vs major depression (score ≥ 21); and CES-D score per 1 SD increase. Models were adjusted for a stroke risk score and behavioral risk factors.

Results:
Of 3309 participants without a history of stroke and with complete CES-D information, 738 (22.3%) had depressive symptoms at baseline. The rate of incident stroke was higher among patients with depressive symptoms than among those without (2.8% vs 2.2%; P = .15). Depressive symptoms at baseline were not associated with greater stroke risk in unadjusted or adjusted models (Table). Major depressive symptoms were associated with a twofold greater unadjusted stroke risk compared with no depressive symptoms. However, this association was not significant after multivariable adjustment.

Conclusions:
In a community-based cohort of African Americans, depressive symptoms were not associated with a greater risk of incident stroke after adjustment for other risk factors.
Abstract W P177: The Frequency and Directionality of the Effect of Sex in Prediction Models for Stroke
Authors: Paulus Jessica , Buettner Hannah , Wessler Benjamin S , Lai Lana , Kent David M
Published: March 2022

Introduction:
There are apparent sex differences in stroke, with women having a higher lifetime risk and worse outcomes. However, there remain critical gaps in our understanding of sex differences in risk, treatment response and outcomes following stroke. We conducted the first systematic summary of the role of sex on stroke-related conditions using a registry of clinical prediction models (CPMs).

Methods:
The Tufts PACE CPM Registry is based on a systematic review of cerebrovascular and cardiovascular CPMs published in English-language articles from 1/1990-5/2012, and includes 585 unique CPMs extracted from 506 articles. All included CPMs permit calculation of outcome probabilities from information provided in the form of an equation, point score or nomogram. We calculated the proportion of models with coefficients for the effect of sex on stroke incidence or prognosis, and summarized the directionality (harmful vs. protective) of the coefficients for sex.

Results:
Out of 75 CPMs with stroke as either an index condition or outcome, 23 (31%) contained a coefficient for sex or presented sex-stratified models. Only 8/48 (17%) models of stroke prognosis included sex or presented sex-specific models, as compared to 14/24 (58%) of models predicting stroke incidence. In models categorized by unique index-outcome pairs, sex was most commonly included in models predicting stroke among a general population (67%). Female sex was associated with reduced risk of mortality after ischemic stroke and a higher risk of stroke from arrhythmias or CABG/PCI. In a general population, women typically had a lower risk of stroke, although stratified models suggest this depends on the presence or absence of other risk factors.

Conclusions:
Sex is an important prognostic factor in CVD but is inconsistently included in stroke CPMs. Sex is more frequently included in models of stroke incidence than models of prognosis. Being female seems protective for some outcomes, but harmful for others.
Abstract W P186: Elevated Brain Natriuretic Peptide Is An Independent Marker For Cardioembolism And Poor Outcome In Acute Ischemic Stroke
Authors: Chaudhuri Jaydip R , Mridula Rukmini K , Balaraju Banda , Bandaru Srinivasarao V , Sharma Vijay K
Published: March 2022

Background:
Brain natriuretic peptide (BNP) is believed to be a diagnostic marker for cardiovascular diseases, including atrial fibrillation (AF). Recent studies have incriminated BNP as a marker of cardioembolic stroke. We aimed at investigating association of plasma BNP levels in acute ischemic stroke subtypes and their outcome in Indian patients.

Methods:
We recruited 270 acute ischemic stroke patients within 48 hours of symptom onset and compared with 110 age and sex matched control subjects. This study was carried out at Yashoda Hospital, Hyderabad, India between April 2011 and March 2013. Serum BNP levels were estimated in stroke patients and control subjects. Good functional outcome at 3-months was defined as modified Rankin score (mRS) ≤2.

Results:
Elevated BNP levels was significantly more in patients with acute ischemic stroke patients 119 (44%) compared to controls 4 (3.6%) (p<0.0001). Among stroke subtypes, elevated BNP levels were observed in 75% of cardioembolic strokes, 45.8% of small artery disease and 43.1 % of larger artery atherosclerosis, 34.5% of stroke of undetermined etiology. On multiple logistic regression analysis, elevated BNP levels was significantly associated with acute ischemic stroke (OR: 13.0, 95%CI:8.1 -15.4). Among stroke subtypes, significant association was seen with cardioembolic stroke (OR: 3.5, 95%CI: 2.2-7.2). Elevated BNP levels were independently associated with poor outcome (OR 3.4, 95%CI:1.2-13.7; p<0.0001) and higher mortality (OR 3.4,95%CI:1.2-13.7; p<0.0001).

Conclusions:
Elevated BNP level is an independent marker for cardioembolic stroke and poor outcome at 90 days follow-up. No significant association was seen with other stroke subtypes.
Abstract W P20: Acute Stroke Following Carotid Endarterectomy: Time for a Paradigm Shift?
Authors: Spiotta Alejandro , Vargas Jan , Zuckerman Scott , Mokin Maxim , Ahmed Azam , Mocco J , Turner Raymond , Turk Aquilla , Chaudry M. Imran , Myers Phil
Published: March 2022

Introduction:
Stroke in the immediate post operative period following carotid endarterectomy (CEA) is usually due to carotid thrombosis. Many centers have begun incorporating angiography before re-exploration, which has the advantage of confirming carotid occlusion and treating tandem intracranial lesions. The aim of this study is to determine the safety and efficacy of this strategy.

Methods:
A retrospective review was performed of all cases undergoing stenting of the carotid artery following carotid endarterectomy from November 2009 to June 2013 at four tertiary care centers. Charts and angiographic images were reviewed. 11 cases of carotid thrombosis within 72 hours of CEA and subsequent stent reconstruction are summarized.

Results:
Five patients had greater than 70% carotid stenosis prior to carotid endarterectomy. One patient had intraoperative occlusion and dissection of the ICA which was noted on intraoperative carotid duplex ultrasound. All patients underwent post operative computer tomography (CT) or computer tomography perfusion (CTP) scans with subsequent cerebral angiography and stent reconstruction within 11 hours of symptom onset. Two patients had tandem middle cerebral artery M3 branch occlusion which was successfully recannalized. In all cases, recanalization was successfully completed between 40 to 160 minutes. There were no procedural complications.

Conclusion:
Emergent endovascular evaluation in the setting of acute post CEA thrombosis is a safe and timely treatment option, with the benefit of detecting and treating embolic intracranial lesions. More investigation is necessary to define the role of immediate angiography and intervention in this rare surgical complication.
Abstract W P208: Weekend Effect on the Utilization of Intravenous Thrombolysis: Myth or Reality in the Era of Regional Tele-Stroke Networks
Authors: Patel Keyur , Hansen Paul A , Gianatasio Ryan , Venizelos Alexander , Bhuva Parita , Shams Tanzila , Chugh Chandril , Nalluri Suman , Coulson Jeff , Guthmann Anita , Janardhan Vallabh
Published: March 2022

Background:
There is a significant shortage of neurologists and specialists especially on the weekends in rural hospitals. Regional Tele-stroke networks are developing across the US, and have enabled 24/7 coverage for the management of acute ischemic stroke. The impact of regional Tele-stroke networks on the utilization of intravenous thrombolysis (IV r-tPA) on weekends remains to be understood.

Methods:
Standardized color-coded algorithms for rapid triage of acute strokes in the emergency room (ER) (Fig: 1) were implemented in 2010 within a regional Tele-stroke network of 122 urban and rural hospitals. All acute stroke consults within the regional Tele-stroke network were prospectively collected in a Tele-stroke registry from January 1, 2012. Demographic factors, days of the week when consultation (Tele-phone or Tele-camera) was performed, time from last known normal (LKN) at time of consultation, and whether IV r-tPA was administered were analyzed. Fisher’s exact
p
-test was used to calculate 2-tailed
p
-values (
p
≤0.05 was consider significant).

Results:
A total of 4,028 consecutive acute stroke consults were performed over a 2 ½ -year period, of which 880 patients had an acute ischemic stroke syndrome within 4.5 hours of LKN. Median age was 65 years (range 16-103 years) and the median NIHSS was 8 (range 0-31). IV r-tPA was given 559 of the 880 patients (63.5%) who met eligibility criteria. Out of the 559 patients, 159 patients were treated with IV r-tpA over the weekend (28.4%,
p
=0.817). There were no gender differences in the utilization of IV r-tPA.

Conclusion:
In the era of Tele-stroke, utilization of IV r-tPA over weekends in urban and rural hospitals is a reality. Establishing regional Tele-stroke networks can help avoid the “weekend effect” in treating acute ischemic stroke patients.
Abstract W P222: Multidisciplinary Public-Private Collaboration Improve Rural Stroke Care
Authors: Thorson Shila , Hyder Shiraz , Beattie Robert , Engelhart Jolene , Halmrast Curt , Arnold Shelly , Herman June
Published: March 2022

Background:
North Dakota has substantially rural demographics with unique logistics, challenges, and other socio-economic complexities affecting timely intervention in stroke patients. The North Dakota Stroke System of Care (NDSSoC) Taskforce was legislatively created in 2009 and implemented, with authority to recommend system changes for state health officer implementation. The NDSSoC Task Force is composed of 11 appointed multidisciplinary members collaborating to provide recommendations in the development of a Stroke System of Care in North Dakota.

Hypothesis:
Implementation of the NDSSoC will result in improved timely interventions and increased quality of care.

Methods:
Quality of care was measured based on data input into the State Stroke Registry (SSR). The SSR utilizes the American Heart Association’s Get with the Guidelines®-Stroke (GWTG-S), an in hospital quality improvement program. The 2010 and 2013 data was compared.

Results:
The percent of acute ischemic stroke patients who arrived at the hospital within 2 hours of time last known well and for whom IV t-PA was initiated within 3 hours increased from 30.9% in 2010 to 80.9% in 2013. Cases receiving a brain CT scan within 25 minutes of arrival to the hospital increased from 16% of patients in 2010 to 25% in 2013. The structure has led to tertiary and state resource investment to support NDSSoC strategies, with a state annual investment of funding equivalent to 59 cents per capita and a state funded FTE coordinator.

Conclusions:
A collaborative statewide effort led by a multidisciplinary team can improve timely intervention and quality of care in stroke. The statewide task force with implementation authority can be successfully applied to areas with a rural demographic.
Abstract W P223: Systems wide Streamlining of Door to Recanalization Processes in Endovascular Stroke Therapy
Authors: Aghaebrahim Amin , Jadhav Ashutosh , Kenmuir Cynthia , Giurgiutiu Dan-Victor , Horev Anat , Saeed Yumna , Callaway Clifton , Guyette Frank , Ducruet Andrew , Jankowitz Brain , Pacella Charissa , Jovin Tudor
Published: March 2022

Objective:
Faster reperfusion leads to better outcome both in thrombolytic therapy and endovascular therapy in acute stroke. We analyzed the effect of interventions aimed to reduce treatment delays in our single-center prospective series.

Methods:
All consecutive ischemic stroke patients treated with endovascular therapy were prospectively registered from 4/20/12 to 7/29/14. We divided the patients into pre-intervention (4/20/12-10/8/13) and post-intervention (10/9/13-7/29/14) period. The main interventions included: awareness, continuous feedback and regular education of staff involved, EMS pre notification, protocolized immediate direct ED attending to stroke attending communication, direct IR activation by stroke team including for possible rather than certain intervention, direct patient transportation by EMS to CT scanner, direct transportation of patient from CT scanner to angiosuite, direct transport from outside hospital to angiosuite.

Results:
See table. There was no significant difference between the demographics, location of the occlusion, rate of IV tpa, or revascularization rate between the groups with the exception of better ASPECT in pre-intervention group (P=0.034). Compared to pre-intervetion, time delays were improved at virtually every step. Median door-to-puncture (D2P) improved from 105 minutes to 67 minutes post-intervention which was significant (p=0.006). Despite time to perfusion improvement, there was no significant difference in rate of 3 month good outcome which is most likely due to small sample size.

Conclusions:
This pilot study demonstrates that D2P times can be dramatically lowered with a few simple measures. Larger prospective studies will be necessary to determine whether these interventions will translate into improved clinical outcomes.
Abstract W P225: Twenty Seven Minute Average Door to Needle Time in a “Stroke Buckle” Emergency Department: Building on
Target: Stroke Best Practice Strategies
with Four Additional Strategies
Authors: Yallapragada Anil V , Benjamin Laura , Neal Cynthia , Saver Jeffrey
Published: March 2022

Background:
The time window for treatment of acute stroke with IV tPA is brief and with every minute wasted there is brain tissue lost. We used the 11 AHA/ASA
Target: Stroke Best Practice Strategies
and four additional care strategies to further streamline our acute stroke protocol.

Methods:
From January 2014 to August 2014, 50 patients were treated with IV tPA at our medical center using a new stroke protocol instituting the 11 AHA/ASA
Target: Stroke Best Practice Strategies
with the addition of 4 strategies: 1) Stroke alert pages initiated by EMS transmitted critical information before patient arrival including a pre-screen for inclusion/exclusion criteria; 2) A standardized pre-stroke order set was enacted by the charge nurse immediately upon the patient arrival; 3) A dedicated “stroke bed” with all necessary stroke tools, stroke box, attached pump for tPA, and weighing capabilities accompanied the patient to CT behind EMS; 4) Patient assessment was initiated by the attending stroke neurologist immediately upon patient arrival in the ED ambulance bay or in the CT scanner. Results: Among the 50 patients, mean age was 65 (SD±14.69), 44.0% were female and mean presenting NIHSS was 11.3 (SD±9.20). The median DTN time was 26.5 minutes (IQR 20-34.5). Categorical DTN treatment times were between 1-20 minutes in 28% (14/50); between 21-30 minutes in 36% (18/50); between 31-60 minutes in 16% (8/50) and more than 60 minutes in 6% (3/50). Median onset of symptoms to treatment time was 78.50 minutes (IQR 56-104). The mean 24-hour post- tPA NIHSS was 4.1. Discharge disposition outcomes were favorable in 82%, including discharge to home in in 70% (35/50) and discharge to acute rehabilitation in 12% (6/50). Outcomes for ambulatory function at discharge were favorable in 84%, including independent ambulation in 70% and ambulation with assistance in 14%. Safety outcomes included sICH in 2% and in hospital mortality in 6%.

Conclusions:
Implementation of
Target: Stroke Best Practice Strategies
plus the four additional care strategies enabled accelerated care with an average DTN time of 27 minutes. The expedited delivery of faster lytic therapy was associated with higher rates of excellent functional outcomes and a favorable safety profile.
Abstract W P234: Mitochondrial Dynamics During Cerebral Ischemia/Reperfusion Injury: The Role of Opa1 in Cytochrome c Release
Authors: Sanderson Thomas H , Bukowski Melissa J , Calo Lesley , Przyklenk Karin , Kumar Rita
Published: March 2022

Background:
Global brain ischemia/reperfusion induces neuronal damage in vulnerable brain regions. A key event leading to neuronal death is mitochondrial cytochrome c (cyt c) release which we have demonstrated is accompanied by release of mitochondrial Opa1, a key mitochondrial fusion protein. We propose that cyt c release is dependent on disruption of Opa1, thus inadvertently promoting fission.

Methods:
Mitochondrial dynamics in vitro were analyzed with real-time imaging of neurons transfected with mito-localized GFP and MR-DEVD to detect caspase activation. Ischemia (OGD) was achieved with a media-gas exchange system and confocal microscopy. Mitochondrial dynamics in vivo was assessed with (i) 3D-electron microscopy to quantify mitochondrial volume, shape, and length and (ii) immunofluorescence for ATP synthase and Opa1.

Results:
Real-time imaging of cells during OGD (A, n=3/group) demonstrated that mitochondria transition from a tubular morphology to a highly fragmented morphology during ischemia. Tubular morphology was rapidly regained in the initial stages of reoxygenation, suggesting fusion remains intact following ischemia. However, mitochondria progressively undergo fragmentation culminating in cell death. Next, we utilized a rat model of cerebral ischemia to evaluate mitochondrial dynamics in vivo. Immunofluorescence (B, n=5/group) and 3D TEM (C, n=3/group) of control brains both exhibit mitochondria with long tubular morphology and Opa1 fluorescence in CA1 neurons was consistent with mitochondrial localization. In contrast, ischemia followed by 6 or 24 hrs of reperfusion resulted in extensive mitochondrial fragmentation (i.e. reduced mitochondrial length<0.05) and loss of Opa1/ATP synthase co-localization (Pearson’s coefficient = 0.63), consistent with Opa1 release and mitochondrial fragmentation.

Conclusion:
These data provide novel evidence that Opa1 may play a role in cell death during brain reperfusion.
Abstract W P237: Overexpression of Soluble Hemopexin as a Therapeutic Tool against Intracerebral Hemorrhage
Authors: Leclerc Jenna L , Dang Alex , Santiago-Moreno Juan , Doré Sylvain
Published: March 2022

Intracerebral hemorrhage (ICH) has the highest morbidity, disability, and mortality rates of any stroke subtype, including ischemic stroke. When a hemorrhagic stroke occurs, the blood-brain barrier is broken and blood components enter the brain. A major cause of morbidity and mortality following ICH is the direct toxicity of blood metabolites, mainly free heme, on adjacent brain tissue. Hemopexin (Hpx) is the endogenous protein responsible for scavenging free heme; thereby, modulating its proxidant and proinflammatory properties. We hypothesized that the specific local overexpression of Hpx within the brain would attenuate anatomical and functional outcomes after experimentally inducing an ICH. We uniquely designed novel adeno-associated viral vectors (and control vectors) to specifically overexpress Hpx locally within the brain of C57BL/6N mice. After experimentally inducing an ICH using the autologous whole blood model, when compared to an identically treated control group, Hpx-overexpressing mice were found to have reduced brain injury volume at 72h post-ICH (p<0.05), as identified by lesion volume quantification of Cresyl Violet stained brain sections (n=7-9/group). Further, these anatomical outcomes were correlated with improved neurologic recovery, as measured by a 24-point neurological deficit scale, at 24h, 48h, and 72h post-ICH (p<0.05). Modulation of hemopexin levels would represent a clinically relevant strategy for the treatment of secondary brain injury following ICH. Further studies are needed in order to evaluate the in vivo utility of hemopexin in attenuating oxidative damage following hemorrhagic brain injury.
Abstract W P240: S1177-eNOS Phosphorylation Protects Against Stroke Injury in Akt1 Deficient Mice
Authors: Atochin Dmitriy N , Huang Paul L
Published: March 2022

Background:
Phosphorylation of eNOS at serine 1177 (S1177) by Akt1 increases NO production and vascular reactivity. The goal of this study is to test the hypothesis that Akt1 deficiency increases susceptibility to stroke because of insufficient eNOS phosphorylation. Thus, constitutively phosphorylated eNOS will overcome Akt1 deficiency and protect against stroke. We generated knock-in mice (S1177D) carrying phosphomimetic mutation (serine to aspartate substitutions) in the eNOS gene. We bred S1177D mice with Akt1 knockout (Akt1KO) mice to test whether constitutively active eNOS could improve stroke outcome in Akt1KO mice.

Methods:
Adult male mice were anesthetized by 30% oxygen, 70% nitrous oxide, and 1.5% isoflurane. Body temperature was maintained at 36-37°C. The common carotid artery was catheterized to measure systemic blood pressure using a blood pressure transducer. For stroke studies we used the middle cerebral artery occlusion (MCAO) by filament with subsequent reperfusion with Laser Doppler cortical blood flow monitoring. Mice were examined for neurologic deficits by 5 point scale 24 hours after stroke. Infarct sizes were determined by the indirect method by 2,3,5-triphenyltetrazolium chloride staining.

Results:
Mean blood pressure was higher in Akt1KO (95±7 mmHg, Mean±SD, n=9) and WT mice (93±3 mmHg, n=8) than in S1177D/Akt1KO mice (80±11 mmHg, n=6, P<0.05). One hour of MCAO with 23 hours of reperfusion produced increased cerebral infarct volume in Akt1KO mice (106±21 mm3, n=9) as compared with WT (70±33, n=9, p< 0.05) mice. S1177D phosphomimetic mutation decreased cerebral infarct volume in Akt1KO mice (64±20 mm3, n=9, P<0.05). This was associated with a functional impairment in the neurologic deficit, as quantities by neurologic scoring (2.7 point deficit for Akt1KO; 1.9 for WT and 1.3 for S1177D/Akt1KO mice).

Conclusion:
Stroke injury was more pronounced in Akt1KO mice than in WT mice. Introducing S1177D mutation in Akt1KO mice resulted in decreased infarct volume, neurological deficit and blood pressure. These results demonstrated that S1177D eNOS-derived NO is able to protect against stroke in the absence of Akt1.
Abstract W P254: Docosahexaenoic Acid Therapy of Experimental Hemorrhagic Stroke
Authors: Belayev Ludmila , Khoutorova Larissa , Hong Sung-Ha , Hong Sung-Ha , Obenaus Andre
Published: March 2022

INTRODUCTION:
Recently we have shown that novel therapy with docosahexaenoic acid (DHA) and DHA complexed to albumin (DHA-Alb) is neuroprotective after ischemic stroke in rats. The purpose of this study was to determine whether treatment with DHA and DHA-Alb would protect against intracerebral hemorrhagic stroke (ICH).

METHODS:
The ICH model was produced in male Sprague-Dawley rats by a double-injection method in which 45 μl of fresh arterial blood was injected into the right striatum. The neurological status was evaluated after ICH (at 50 min) and at 1h, 1, 2, 3 and 7 days after treatment; a grading scale of 0-12 was employed (normal score=0, maximal deficit=12). Six groups we studied: DHA (5 mg/kg), Alb (0.63 or 1.25 g/kg), DHA-Alb (5 mg/kg+0.63 g/kg or 5 mg/kg+1.25 g/kg) or saline were administered i.v. at 60 min after ICH (n=10-12 per group).
Ex vivo
imaging of the brains was conducted on 11.7T MRI on day 7. High-resolution T2 weighted images (T2WI) and apparent diffusion coefficient maps were generated. After completion of the MRI study, histopathology and immunochemistry were conducted and hematoma volumes were determined.

RESULTS:
The physiological variables were entirely comparable among the six groups. Treatment with DHA significantly improved behavior on days 1, 2, 3 and 7 (by 25-32) and reduced hematoma volume by a mean of 33% compared to saline group. Animals treated with low and moderate doses of DHA-Alb showed an improved neurological score compared to corresponding Alb groups on day 1 (23 and 26%), day 2 (32 and 31%), day 3 (34 and 33%) and day 7 (31 and 36%, respectively). MRI revealed a consistent hematoma involving the striatum and overlying corpus callosum. Moderate doses of DHA-Alb reduced hematoma volumes compared to Alb group (by 42%). Low dose of DHA-Alb also reduced hematoma volumes, but it was not statistically different from Alb group. Lesion volumes computed from T2WI images and by histopathology agreed closely with one another and were highly correlated.

CONCLUSION:
We concluded that both, DHA and DHA-Alb therapy provides neurobehavioral recovery and reduces hematoma volume when administered at 1h after ICH in rats.
Abstract W P267: Different Strokes: Causality and Outcomes in the NINDS-tPA Trials
Authors: Liebeskind David S , Choi Arthur , Sanossian Nerses , Fang Scot , Darwiche Adnan , Scalzo Fabien
Published: March 2022

Background:
Predictive models of outcome after acute ischemic stroke utilize regression methods that discern only associations between variables. Causality, or the nature of relationships between myriad variables collected in clinical trials, has not been considered. We investigated whether NIHSS strata of stroke severity disclose distinct interactions amongst clinical variables, imaging, treatment and outcomes in the NINDS tPA Trials.

Methods:
The public dataset of the NINDS tPA Trials was analyzed based on NIHSS strata of <10, 10-14, 15-19 and ≥20. For each cohort, causal links were established for relationships between age, sex, co-morbidities, imaging features, timing features, thrombolytic treatment and subsequent 90-day mRS. Each variable was normalized to the interval [0, 1] and missing input samples replaced using regression predictions. The PC causal discovery algorithm used conditional independence tests between variables, incorporating temporal details. Statistical dependencies were established at p-value of 0.1 on the Fisher's z test.

Results:
624 subjects (mean age 66.9 years, 58% female) were included. Overall, significant causal links were identified between clinical variables, CT findings and clinical outcomes after thrombolysis. Subgroup analyses on NIHSS strata, however, revealed distinct causal links at each strata. For NIHSS≥20, age and 7-day imaging findings were directly linked with 90-day mRS, followed by treatment and clinical or imaging findings. At NIHSS 15-19, the strength of treatment interaction was not as prominent. At NIHSS 10-14, treatment and 7-day imaging were closest linked with outcome, over other variables. At NIHSS<10, 7-day imaging and clinical variables other than age were closest linked with outcome. Initial imaging variables and even time from onset to treatment exhibited different relationships with outcomes when causality was considered.

Conclusions:
NIHSS strata of stroke severity in the NINDS-tPA Trials demonstrate different relationships between clinical, imaging and treatment variables with outcomes. Causal relationships, not just associations, provide novel insight on stroke outcomes to inform future clinical trial design and decision-making.