bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P260: Role of the Prostaglandin E2 EP1 Receptor in Traumatic Brain Injury
Authors: Glushakov Alexander V , Fazal Jawad A , Narumiya Shuh , Dore Sylvain
Published: July 2021

Introduction:
Brain injuries promote upregulation of so-called proinflammatory prostaglandin E2 leading to overactivation of a class of its cognate G-protein coupled receptors, notably EP1, which is considered as a promising target for treatment of ischemic stroke and, possibly, other neurological disorders involving excitotoxicity. However, our recent data suggest that of EP1 receptor in intracerebral hemorrhage may play a protective role. The goal of this study was to investigate a translational potential of EP1 receptor for treatment of traumatic brain injury (TBI).

Methods:
The acute brain injury was induced using controlled cortical impact (CCI) in wildtype (WT) and genetic EP1 receptor knockout mice (EP1-/-). Neurological deficit scores (NDS) and anatomical brain pathology were accessed at 48h after injury.

Results:
CCI resulted in significant cortical lesions, localized hippocampal edema and neurological deficits compared to animals from sham group underwent craniotomy only. The NDS after CCI were significantly higher in older mice (7-11mo) compared to young adult animals (2-4mo) in both WT and EP1-/- groups. Treatment with a selective antagonist SC-51089 with repeated doses of 20-100μg/kg after CCI had no significant effects on cortical lesions, hippocampal edema and NDS in young adult mice of both WT and EP1-/- genotypes. Post-treatment with 17-pt-PGE2 (300μg/kg) had no significant effects on anatomical brain pathology in young adult mice, but improved NDS at 24h in WT but not in EP1-/- mice. Immunohistochemistry revealed significant increases in GFAP and Iba1 immunoreactivity in selected brain regions surrounding injury suggesting astrogliosis and microglia activation. EP1 receptor knockout had no effects on GFAP and Iba1 expression in young adult mice, whereas lead to a significant attenuation of GFAP immunoreactivity in older mice.

Conclusions:
This study provides, for the first time, a clarification on the role of EP1 receptor in a preclinical model of contusive TBI. The results suggest that EP1 receptor might be involved in complex pathways differentially associated with neurological deficits. In addition, this study provides further clarification on clinical use of EP1 receptor ligands for treatment of acute brain injuries.
Abstract W P266: A Simple Score for Prediction of Outcome after Cerebral Venous Thrombosis
Authors: Barboza Miguel A , Chiquete Erwin , Arauz Antonio , Colín Jonathan , Quiroz-Compean Alejandro , Cantú-Brito Carlos
Published: July 2021

Background and purpose:
Cerebral venous thrombosis (CVT) not always implies a good prognosis. There is a need for robust and simple classification systems of severity after CVT that help in clinical decision-making.

Methods:
We studied 467 patients (81.6% women, median age: 29 years, interquartile range: 22-38 years) with CVT who were hospitalized from 1980 to 2014 in two third-level referral hospitals. Bivariate analyses were performed to select variables associated with 30-day mortality to integrate a further multivariate analysis. The resultant model was evaluated with the Hosmer-Lemeshow test for goodness of fit, and on Cox proportional hazards model for reliability of the effect size. After the scale was configured, security and validity were tested for 30-day mortality and modified Rankin scale (mRS) >2. The prognostic performance was compared with that of the CVT risk score (CVT-RS, 0-6 points) as the reference system.

Results:
The 30-day case fatality rate was 8.7%. The CVT grading scale (CVT-GS, 0-9 points) was integrated by stupor/coma (4 points), parenchymal lesion >6 cm (2 points), mixed (superficial and deep systems) CVT (1 point), meningeal syndrome (1 point) and seizures (1 point). CVT-GS was categorized into mild (0-3 points, 1.1% mortality), moderate (4-6 points, 19.6% mortality) and severe (7-9 points, 61.4% mortality). For 30-day mortality prediction, as compared with CVT-RS (cut-off 4 points), CVT-GS (cut-off 5 points) was globally better in sensitivity (85% vs 37%), specificity (90% vs 95%), positive predictive value (44% vs 40%), negative predictive value (98% vs 94%), and accuracy (94% vs 80%). For 30-day mRS >2 the performance of CVT-GS over CVT-RS was comparably improved.

Conclusion:
The CVT-GS is a simple and reliable score for predicting outcome that may help in clinical decision-making and that could be used to stratify patients recruited into clinical trials.
Abstract W P273: The Cost-Effectiveness of Telestroke Varies by Implementation Cost and Stroke Severity: Real World Data From a Pacific Northwest Network
Authors: Baraban Elizabeth , Nelson Richard , Lesko Alexandra , Majersik Jennifer , Bhatt Archit , Okon Nicholas
Published: July 2021

Objective:
An obstacle for community hospitals in joining a telestroke network is often the cost of implementation. Yet, previous analyses examining the cost and cost-effectiveness have only used estimates from the literature. Using real-world data from a Pacific Northwest telestroke network, we examined the cost-effectiveness of telestroke for spokes by level of financial responsibility for these costs and how this changes with patient stroke severity.

Methods:
We constructed a decision analytic model and parameterized it using patient-level clinical and financial data from the Providence Telestroke Network (PTN) pre and post telestroke implementation. Data included patients presenting at 17 spokes within 4.5 hours of symptom onset. Probability inputs included observed IV-tPA treatment rates, transfer status and hospital costs and reimbursements. Effectiveness, measured as quality-adjusted life years (QALYs), and cost per patient were used to calculate incremental cost effectiveness ratios (ICERs). ICER’s of <$50,000-$120,000/QALY are considered cost-effective. Outcomes were generated overall and separately by admit NIHSS, defined as low (0-10), medium (11-20) and high (>20) and percentage of implementation costs paid by spokes (0%, 50%, 100%).

Results:
Data for 594 patients, 105 pre- and 489 post-implementation, were included. See Table 1.

Conclusions:
Our results support previous theoretic models showing good value, overall. However, costs and ICERs varied by stroke severity, with telestroke being most cost-effective for severe strokes. Telestroke was least cost effective if spokes paid for half or more of implementation costs.
Abstract W P274: Characterizing The “Universe” Of Transitional Care Programs For Stroke Survivors In The United States
Authors: Abir Mahshid , Vickrey Barbara G , Koegel Paul , Broderick Joseph P , Suter Robert , Watson Sam R , Watson Sam R , Barsan William G
Published: July 2021

This study’s purpose is to characterize the range of TC programs for stroke survivors in a national sample of healthcare facilities in the U.S., as an initial step toward ultimately associating those characteristics with TC program outcomes.

Hospitals in the following networks were invited to complete an electronic survey: The National Institute of Neurological Disorders and Stroke’s Neurological Emergencies Treatment Trials network and StrokeNet, the American Heart Association’s Get With The Guidelines hospitals, and the Michigan Health & Hospital Association. The survey inquired whether the facilities have stroke TC programs, program description, number of patients seen annually, facility type, and healthcare context.

Out of 82 respondents, 65 hospitals reported a TC program, and 17 did not have such programs. Respondents include facilities from all five U.S. geographic regions. The 42 facilities that reported the annual number of patients served, served between 48.0-1974.0 patients (median 426.0, inter-quantile range 245.0-840.0). Of the facilities that reported hospital type, 23 (57.5%) are academic, 7 (17.5%) are academic affiliates, and 10 (25%) are community. Of the 25 facilities that reported the healthcare setting in which the TC program is delivered, 12 (48%) are delivered in a fee-for-service, 6 (24%) in integrated delivery system, 3 (12%) in traditional primary care, and 1 (4%) in a patient-centered medical home. TC program components reported (in descending order of frequency) include: Support services, call-backs, transitional planning, inpatient physical rehabilitation, care coordination, neurology follow up, telemedicine, home visits, anytime access. Of the 61 facilities that provided information regarding the TC program components 33 (51%) have one, 15 (23%) have two, 8 (12%) have three, and 5 (8%) have four components.

This survey found substantial heterogeneity in TC programs. A standardized definition of TC program components is not available, hence the necessary first step in studying comparative effectiveness of TC programs is building a taxonomy of TC program components. This will enable analysis of the most effective TC programs, and ultimately guide improving the TC experience and outcomes for stroke survivors.
Abstract W P291: Long-term Stroke Awareness Among Stroke Survivors is Suboptimal
Authors: Corado Carlos , Bergman Deborah , Ruff Ilana , Curran Yvonne , Bernstein Richard A , Prabhakaran Shyam
Published: July 2021

Background/Objective:
Stroke survivors are at high-risk for recurrent stroke. Stroke education attempts to reduce this risk by emphasizing stroke warning signs and need to call 911. Long-term stroke awareness has been under-studied in stroke survivors. We aimed to assess stroke awareness at 1 year among stroke survivors and identify factors associated with poor performance.

Methods:
From a single center prospective cohort study of consecutive patients diagnosed with acute ischemic stroke or transient ischemic stroke (TIA), we identified stroke survivors able to complete telephone interviews at 1 year. All patients were provided standardized educational materials during index hospitalization. We used the validated Stroke Action Test (STAT) to assess stroke knowledge at 1 year. The STAT is a 28-item questionnaire that asks respondents to choose 1 of 4 answers to each scenario (call 911, call doctor, wait 1 hour, or wait 1 day). We also assessed cognitive status at 1 year using the validated telephone interview for Cognitive Status (TICS). We identified factors associated with STAT score (number of correct responses) using univariate and multivariate regression.

Results:
Among 254 patients who completed 1 year follow-up (65.8 years; 55.5% male; 68.5% white; 94.1% modified Rankin 0-1 at 1 year), the median STAT score was 57.1% (range 2.1-75.0%). In multivariate regression, TICS score (B=0.533; p<0.001) and ethnicity (B=-2.357, p=0.006) were independently associated with STAT score. Age, race, insurance, arrival by ambulance at time of index hospitalization, stroke unit admission, length of stay, discharge to rehabilitation, post-stroke hospital/clinic visits were not associated with STAT score.

Conclusion:
Despite hospitalization and standardized education at time of index event, most stroke survivors are unaware of stroke warning signs at 1 year. Besides cognitive status and Hispanic ethnicity, no other factors were identified that predicted STAT score performance. Future studies should focus on improving hospital-based stroke educational programs and consider novel strategies in patients with cognitive impairment and differing language/cultural backgrounds.
Abstract W P293: Opportunities For Interventions In Stroke-Dizziness Presentations: A Prospective Single Center Surveillance Study
Authors: Kerber Kevin A , Burke James F , Brown Devin L , Hofer TImothy P , Adelman Eric E , Callaghan Brian C , Fendrick A. M , Meurer William J
Published: July 2021

Objective:
Ischemic stroke can be a diagnostic dilemma in presentations of acute dizziness and increased resources will likely be required to reduce instances of misdiagnosis. To inform the potential value of the deployment of increased resources, we sought to describe opportunities for therapeutic interventions from a series of acute dizziness-stroke patients who had diagnostic uncertainty (i.e., only mild or no general neurologic deficits) on presentation.

Methods:
Active and passive surveillance methods were used at a tertiary care center to identify acute dizziness patients with nystagmus or imbalance, excluding those with benign paroxysmal positional vertigo, medical causes, or moderate-to-severe neurologic deficits. Stroke was defined as any acute infarction on a clinical or research MRI performed within 14 days of dizziness onset.

Results:
From November 21, 2009, to March 29, 2013, we identified 26 patients with acute ischemic stroke presenting with dizziness and either mild or no general neurologic deficits. Infarction volume was small (<1cm3) in 19 (73%), moderate (≥1-<10cm3) in 2 (8%), and large (>10cm3) in 5 (19%). The proportion of cases arriving within 3, 4.5, and 6 hours of symptom onset was 38% (10), 38% (10), and 46% (12). Two cases were treated with thrombolysis. Half of all cases were already prescribed a statin medication at the time of presentation and 42% (11) were already prescribed an antiplatelet or anticoagulant. One patient met clinical eligibility for sub-occipital craniectomy. Three patients were discharged to a skilled nursing facility (1) or acute rehabilitation (2), whereas the majority (22; 85%) were discharged home.

Conclusion:
In this single center study which used rigorous surveillance and imaging-based methods to capture cases of acute dizziness-ischemic stroke with only mild or no general neurologic deficits, we found that a minority of patients met time requirements for acute treatments, nearly half were already on secondary prevention medications, and the majority did not require discharge to a skilled nursing facility or acute rehabilitation.
Abstract W P330: Intracerebral Hemorrhage Volume Measurement: Modified ABC/2 Method is Faster and Reliable
Authors: Kumar Abhay , Shetty Vilaas
Published: July 2021

Background:
Intracerebral hemorrhage (ICH) volume calculation using ABC/2 method is well established and is widely used. Modifications of the method have been proposed which can make hematoma volume measurement faster. Helical computed tomographic (CT) techniques with multiplanar reconstructions allow direct measurement of the antero-posterior (AP), transverse (TV) and craniocaudal (CC) diameters, thereby allowing calculation of the hematoma volume using a modified ABC/2 method. We investigated the reliability of the modified ABC/2 technique of ICH volume measurement.

Method:
Forty-one consecutive patients with ICH were identified from a 6-month period following review of the medical records. A board-certified neurologist used the established ABC/2 formula, while a board-certified neuroradiologist used the modified ABC/2 formula to calculate the ICH volumes. The neuroradiologist took the AP measurements off the axial section while TV as well as CC measurements off the coronal images. Statistical analysis was performed.

Results:
The neuroradiologist took significantly less time (9 ± 3seconds) in measuring the volumes as opposed to the neurologist (44 ± 12 seconds), p<0.001. The average ICH volume as measured by the neurologist (13.2 ± 16.4 cc) was significantly smaller than the neuroradiologist measured

ICH volume (19 ± 32 cc), p <0.001. When hematoma volume was dichotomized with 30 cc as the cutoff, the examiners agreed on volumes of < 30 cc more often (95%) than the volumes of > 30 cc (66%). The volumes measured using the two methods were significantly correlated (r= 0.85, p<0.001) with a high inter-rater reliability (Cronbach’s alpha= 0.82, ICC= 0.8). For individual dimensions, the agreement was least for TV diameters (Cronbach’s alpha = 0.7, ICC= 0.7) and highest for AP diameters (Cronbach’s alpha = 0.95, ICC= 0.95).

Conclusion:
The modified ABC/2 formula can quickly and reliably measure the hematoma volume based on our findings. We plan to test reliability and validity further with a larger examiner pool before its routine clinical application is suggested.
Abstract W P337: Using Simulation Mannequins to Train Nurses in Stroke Dysphagia Screening
Authors: Freeland Tonya , Garrett Racquell , Pathak Shweta , Anderson Jane A , Daniels Stephanie K
Published: July 2021

Background and Purpose:
Screening patients admitted with stroke symptoms for risk of dysphagia is often the responsibility of registered nurses (RNs). Simulation technology has become a widely used evidence-based form of training for healthcare professionals. Simulation mannequins allow for training in a controlled environment, eliminating the need for practice of skills with live patients. The purpose of this pilot study was to compare effectiveness of in-service training to a comprehensive training method utilizing a medical simulation mannequin as a main component to teach administration of swallowing screening items.

Methods:
RNs (N=32) were randomly assigned to one of two training groups. Both groups received a 20 minute didactic training in administration and interpretation of non-swallow (dysarthria, wet voice, abnormal volitional cough) and water swallow (cough, throat clear, wet voice) screening components. The control group (n=16) received only didactic training. The experimental group (n=16) received didactic training plus additional training with a medical mannequin programmed to simulate auditory elements of acute stroke patients, e.g., dysarthria, cough after swallow. Acquisition of skills was evaluated for both groups using the medical mannequin simulated with various stroke patient profiles. Fisher’s Exact Test was used to assess the association between type of training and acquisition of skills.

Results:
No significant association was evident for acquisition of interpretation or procedural skills between groups. Raw data revealed that the experimental group achieved accurate interpretation and procedural skills in fewer trials than the control group. This was particularly evident for procedural skills in which 69% in the experimental group achieved accurate administration within one trial while only 31% in the control group demonstrated accuracy.

Conclusion:
Results indicate that simulation training is a feasible method to teach and evaluate obtainment of skills necessary to accurately complete dysphagia screenings in acute stroke patients. Further research should focus on retention of skills learned and translation of skills from the simulated patient to live patients admitted with stroke symptoms.
Abstract W P344: Being the Change You Wish to See: Reducing the Incidence of False-Positive Catheter-Associated Urinary Tract Infections in a Neuroscience Population
Authors: Lester Sarah , Branson Pamela
Published: July 2021

Background and Purpose:
The formation of a bacterial biofilm on an indwelling urinary catheter is considered to be a leading cause for diagnosed urinary tract infections in the intensive care setting (Djeribi, Bouchloukh, Jouenne, & Menaa, 2012). Bacterial biofilms (colonization) are thought to develop between one to five days (Saint & Chenoweth, 2003). Neuroscience patients are of particular interest when examining biofilm formation, as their underlying disease processes pose unique challenges to decreasing indwelling catheter device days, including neurogenic bladder, need for euvolemic fluid volume states, et cetera. The purpose of this quality improvement initiative was targeted at reducing the number of diagnosed false-positive CAUTI.

Methods:
For a period of February 2014- July 2014, nurses in two neurosciences intensive care units at a large academic center piloted an intervention targeted at reducing the number of diagnosed false-positive CAUTI, thought to occur as a result of catheter colonization or biofilm formation. For the intervention, patients who received an order for a urine culture who had an indwelling catheter for equal to or greater than five days had their indwelling catheter changed. Urine cultures were subsequently obtained from the new indwelling catheter.

Results:
Data for the months ( February 2014-July 2014) included a total of 87 patients from the neurosciences intensive care units who met the criteria for an indwelling catheter change, in the event that they had a urine culture ordered on or after device day five. Twenty six patients had their indwelling catheter changed prior to urine specimens being obtained. Five of the twenty six obtained from the new indwelling catheters demonstrated growth at the time the reports were finalized. Compared to previous CAUTI rates for the same time period in 2013 we have reduced the absolute numbers from 30 to 13.

Conclusions:
The organization’s infection control board reviewed the data and permission was granted to extend the pilot to all adult ICU. The preliminary data does suggest bacterial biofilm may contribute to the rate of CAUTI in the neuroscience population.
Abstract W P345: Strength in Numbers: Stroke Coordinators Improving Care Through Collaboration
Authors: Morrison Kathy ,   Stroke Coordinators of Pennsylvania (SCoPA)
Published: July 2021

Background:
Stroke care evolution has been remarkable since 2000, when the Brain Attack Coalition published their recommendations for Primary Stroke Centers. For the first time, hospitals had evidence-based standards to improve patient outcomes. Today, many states require emergency responders to take suspected stroke patients only to certified stroke centers. As a result, many hospitals have established the role of stroke coordinator to oversee the myriad facets of stroke care. Coordinators are overwhelmed with the opportunities - and responsibilities - to improve care processes.

Method:
In 2009, the stroke program manager at a Magnet academic medical center established a regional stroke coordinators’ group. Eight coordinators met and established milestones for success. Information has been shared and nurses have traded services, providing education for each other’s organization. The group of now 28 coordinators meets every other month.

Results:
Positive outcomes of membership in this dynamic group include a 65% increase in professional membership in American Association of Neuroscience Nurses. In addition, the coordinators report confidence and empowerment to impact change in their own organization that improved care and outcomes. Aggregate group data demonstrates improvement in the following measures: thrombolytic administration 44%; door-to-needle time 16%; & patient education 12%. Nine additional hospitals (from 6 to 17, a 183% increase) have attained Advanced Primary Stroke certification and the host organization achieved Comprehensive Stroke certification.

Conclusion:
Neuroscience nurses are influential leaders - not just within their own organization. These outcomes demonstrate the mutual benefit of stroke coordinator colleagues working together and sharing best practice strategies. Through multi-organizational collaboration, they have become empowered to establish programs and become experts within their organization, able to guide and improve the care provided by their own direct-care nurses.
Abstract W P35: Is it Safe for Patients with Acute Cervical Vertebral Artery Dissection to Rotate Their Head During the Early Period of Dissection?
Authors: Kim Stanley H , Dhablania Nathan K , Kim Joshua J , Tutanes Jennifer B , Chai Christian H
Published: July 2021

Introduction:
The authors present a prospective series of 4 consecutive patients with symptomatic acute spontaneous cervical vertebral artery dissection (VAD) in which a dynamic catheter cerebral angiogram conclusively demonstrated adverse near complete or complete occlusion of the dissected VA associated with rotation of the head. We present clinical and angiographic data and management of these patients not previously reported in the literature.

Methods:
From 2012 to 2014, we performed a prospective study of 4 consecutive patients with spontaneous acute cervical VAD. We reviewed initial and follow up clinical data and diagnostic imaging including magnetic resonance angiogram (MRA) or computed tomographic angiogram (CTA) of head and neck and dynamic catheter cerebral angiogram.

Results:
A total of 4 patients (Age 36 +/- 5.4; M=3, F=1) presented with acute cerebellar or brain stem stroke due to a total of 6 cervical VAD at the level of V3 (N=4) and V2 (N=2) segments diagnosed by CTA or MRA. Initial mRS and NIHSS scores on admission were 3 +/- 0.8 and 1.5 +/-1, respectively. Dynamic cerebral angiogram performed with patient’s head in neutral position showed VAD with average stenosis of 74.16 % +/- 20.59. Near complete or complete occlusion of the dissected VA was observed and associated with worsening neurological symptoms when the head was rotated beyond 45 degrees to the right side (N=3) and left side (N=3). All patients were treated with daily Aspirin and Plavix for at least 3 months and placed on cervical collar for one month to prevent rotational occlusion of VA. Repeat dynamic cerebral angiogram at 2.5 months +/- 1.91 showed resolution of the VAD. Clinical follow up evaluation at 11.5 months +/- 8.5 showed mRS score of 1.5 +/- 1.0 and NIHSS score of 0.75 +/- 0.96 with no recurrence of stroke.

Conclusion:
Patients with cervical VAD may be at risk of developing ischemic or embolic stroke associated with rotation of the head. Current diagnostic imaging studies are performed with the patient’s head in neutral position and fail to show dynamic changes of VAD.

The authors emphasize the importance of performing dynamic cerebral angiogram during the evaluation of patient with VAD and consider changes in the Guidelines on the Diagnosis and Management of Cervical VAD.
Abstract W P371: Periodontal Disease is Associated with Aortic Arch Atheroma a Marker of Recurrent Vascular Events in Stroke/TIA Patients
Authors: Chung Matthew , Hinderliter Alan , Offenbacher Steven , Beck James , Sen Souvik
Published: July 2021

Background:
Periodontal disease (PD) is independently associated with recurrent vascular events in Stroke/TIA. Aortic arch atheroma (AA) is an independent risk factor for stroke. The association between PD and AA has not been described.

Objective:
To test the association between: 1) significant AA and recurrent vascular event in stroke/TIA 2) PD and AA (plaque severity and characteristics)

Methods:
In this prospective longitudinal hospital-based cohort study, PD was assessed in Stroke/TIA patients. Based on clinical measures patients were classified to have high (HPD) versus low periodontal disease (LPD). As part of their stroke work-up, AA was assessed using transesophageal echocardiogram (TEE). Based on plaque thickness the AA was graded as mild (0-0.99 mm), moderate (1-3.99 mm) or severe (≥4 mm), as well as plaque characteristics, namely mobility, ulceration and calcification. The patients were followed up for recurrent vascular events, namely stroke, TIA, myocardial infarction and vascular death.

Results:
In an eighteen-month period, 106 patients were evaluated, 40(38%) showed HPD and 27 (26%) had recurrent vascular events over a median of 24 months (range 12-24 months). AA assessed by TEE revealed 16 with mild, 73 with moderate, and 17 with severe plaque. Those with severe AA had a higher rate of recurrent vascular event compared to those without (Figure). Severe AA was associated with recurrent vascular events (HR 2.3, 95% CI, 1.02-5.32). HPD patients had higher (p = 0.004) AA plaque thickness (Mean±SD 2.0±2.4 mm) compared with LPD (1.6±1.2 mm). HPD was associated with moderate AA (OR 10.5, 95% CI, 1.3-84) and severe AA (OR 16.9, 95% CI, 1.8-158). Among plaque characteristics HPD was associated (p=0.02) with calcification.

Conclusion:
In stroke/TIA patients severe AA is associated with recurrent vascular events. HPD is associated with an increased AA plaque thickness and calcification. The results suggest that PD may be a risk factor for AA.
Abstract W P403: Interleukin-6 Is Regulated By Let7 In Ischemic Stroke
Authors: Jickling Glen , Shroff Natasha , Ander Bradley P , Liu Dazhi
Published: July 2021

Background:
Interleukin-6 (IL-6) is increased in ischemic stroke and associated with increased mortality and morbidity. microRNA are important regulators of inflammation and may be central to IL-6 expression in stroke. In this study we evaluated the regulation of IL-6 by microRNA in ischemic stroke.

Methods:
IL-6 and microRNA were evaluated in circulating leukocytes of patients with ischemic stroke (n=106) and vascular risk factor controls (n=106). In a culture model of monocyte activation following stroke, the effect of let7 transfection on IL-6 expression was evaluated.

Results:
In patients with ischemic stroke let7 microRNA was found to be decreased compared to risk factor controls (corrected p<0.01, fold change<1.4). This decrease correlated with an increase in IL-6 gene expression. In culture, stimulated monocytes expressed increased IL-6. Transfection of let7 mimic decreased IL-6 expression, whereas let7 inhibitor increased IL-6 expression. This effect was dependent on toll-like receptor 4 (TLR4) activation, and could be abolished with the TLR4 inhibitor Tak242.

Conclusions:
Il-6 expression is regulated by microRNA let7 in ischemic stroke and thus may be an important determinant of post-ischemic cerebral inflammation.
Abstract W P421: Trend in Concurrent Hospitalization for Moyamoya and Sickle Cell Disease: An Analysis of Nationwide Inpatient Sample Data
Authors: Busani Sudharani , Nadkarni Girish N , Patel Achint , Ammakkanavar Natraj , shah Hardik kumar , Patel Urvish , Simoes Priya , Jain Vishal B
Published: July 2021

BACKGROUND:
The association between Moyamoya disease and sickle cell disease is well recognized in the literature. However, there is limited data on inpatient admission of concurrent sickle cell disease and Moyamoya disease. We sought to determine the trend in incidence of admissions of concurrent Moyamoya and sickle cell disease as well as the most common presentation of these admissions.

METHODS:
We reviewed the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (NIS) database from 2000-2011 for concurrent Moyamoya and sickle cell admissions using the ICD 9-CM codes We obtained data on gender, clinical presentation, procedures, co-morbidities and patient outcomes

RESULTS:
From 2000 to 2011, an estimated patients 756 (weighted (n)=3692) with co-existing Moyamoya disease and sickle cell disease were admitted. The incidence of admission for concurrent disease increased significantly from 0.04/100,000 admissions in 2000 to 0.21/100,000 admissions in 2011(figure 1). This was very significant using the Cochrane Armitage trend test(p<0.001). The most likely reasons for admissions were ischemic stroke(7.2)% followed by hemorrhagic stroke(2.8 and transient ischemic attack(1.2%) (p = 0.0116). The most commonly performed treatment procedures included packed cell transfusion(33.7%) followed by exchange transfusion (8.8%). However there was no significant change in mortality from 2000-2011.

CONCLUSION:
The number of hospitalizations due to concurrent Moyamoya and sickle cell disease has increased significantly over the last decade and are likely to present with a cerebrovascular accident. Thus, it is important to maintain a high degree of suspicion for Moyamoya disease in sickle cell disease patients presenting with neurological symptoms since this could potentially impact their management.
Abstract W P422: ABC/2 Does Not Accurately Predict Volume of Arteriovenous Malformations
Authors: Roark Christopher D , Vadlamudi Venu , Stetler William R , Gemmete Joseph J , Chaudhary Neeraj , Hayman James , Thompson B. G , Pandey Aditya
Published: July 2021

Introduction:
Stereotactic radiosurgery (SRS) represents an important method of curing arteriovenous malformations (AVMs) and preventing associated hemorrhages. The decision to proceed with SRS is commonly based on calculated nidal volume, as smaller AVMs are more likely to obliterate. When counseling patients for SRS, physicians commonly use the ‘ABC/2’ method. We aim to understand whether such an approximation is accurate when compared to the exact volume calculated from thin-cut axial sections used for SRS planning.

Hypothesis:
AVM volume calculated by the ‘ABC/2’ method on digital subtraction angiography (DSA) is significantly different than the volume calculated using SRS planning techniques.

Methods:
85 AVMs treated with SRS were identified from our database. Maximum nidal diameters in orthogonal planes on DSA images were recorded to determine volume by the ‘ABC/2’ formula. The nidal target volume was extracted from operative reports of SRS. The volumes were then compared using descriptive statistics and the paired t-test.

Results:
The average volume was 7.1 cm
3
(SD 7.94) when using SRS planning methods, and 11.2 cm
3
(SD 15.6) when using the ABC/2 methodology. Moderate correlation was seen between ABC/2 and SRS (r = 0.657; p <0.001). Paired samples T-test revealed significant differences between the SRS volume and ABC/2 (t = -3.2; p = 0.002). When the AVMs were stratified based on an ABC/2 volume, the significant differences remained (t = -2.1; p = 0.046 for ABC/2 volume less than 7 cm
3
and t= -4.2; p <0.001 for ABC/2 volume greater than 7 cm
3
). Comparisons of AVM volume using SRS planning techniques with analysis utilizing equations for the volumes of various shapes (cones, cylinders, and spheres) demonstrated significant differences with cones and solids (p < 0.001 in both) while spherical volume was statistically indistinguishable from SRS planning volumes (p = 0.388).

Conclusions:
‘ABC/2’ on DSA is not an accurate method of calculating AVM nidal volumes as it overestimates the volume by 57.7%. As a result, practitioners may choose not to offer SRS - incorrectly concluding that a particular AVM is too large to have an appropriate response to SRS. We propose that SRS planning techniques should be utilized before counseling patients on treatment.
Abstract W P43: Extent of “Blooming Effect” Predicts Middle Cerebral Artery Recanalization After Intravenous Thrombolysis
Authors: Yan Shenqiang , Lou Min
Published: July 2021

Background and Purpose:
Hemosiderin was shown to have a stronger T2 shortening effect than deoxyhemoglobin. Therefore, the extent of “blooming effect” of susceptibility vessel sign (SVS) might represent composition of different iron forms. We aimed to investigate the relationship between extent of overestimation of thrombus burden and middle cerebral artery (MCA) recanalization.

Methods:
We retrospectively examined clinical and imaging data from consecutive acute ischemic stroke patients with MCA occlusion who underwent MRI before and 24 hours after IV thrombolysis in our hospital. A delayed phase contrast enhanced T1-WI was used to measure the true size of thrombus. We then examined the association of MCA recanalization and extent of overestimation of thrombus burden.

Results:
We observed the presence of MCA SVS in 44 patients on initial gradient-recalled echo (GRE) scans and MCA recanalization in 21 (47.7%) patients 24 hours after treatment. The extent of overestimation of thrombus width on GRE was an acceptable predictor for MCA recanalization (odds ratio 1.584 per 10%; 95% CI: 1.090 to 2.310; p=0.016), with a receiver-operator characteristic of 0.884 (95% CI: 0.780 to 0.988; p < 0.001). The optimal cut-off point for predicting recanalization was identified at 1.7814, and this yielded a sensitivity of 87.0% and a specificity of 85.7%.

Conclusions:
Overestimation of thrombus burden on GRE might reflect the content of hemosiderin. A larger overestimation might indicate aged thrombus, which were resistant to thrombolysis.
Abstract W P54: Cardioembolic Strokes Have an Improved Clinical Outcome Following Intravenous Thrombolysis in Comparison With Strokes Caused by Large Vessel Disease
Authors: Schmitz Marie Louise , Simonsen Claus Z. , Mikkelsen Irene K. , Svendsen Marie Louise , Larsson Heidi , Madsen Mette , Fisher Marc , Johnsen Soeren , Andersen Grethe
Published: July 2021

Introduction:
Ischemic stroke prognosis given standard therapy differs according to the underlying pathophysiology. In contrast, the impact of ischemic stroke subtype on clinical outcome in patients treated with intravenous tissue-type plasminogen activator (IV-tPA) is less clear.

Objectives:
We examined the association between ischemic stroke subtype and clinical outcome in magnetic resonance imaging (MRI)-selected patients treated with IV-tPA.

Methods:
We included consecutive MRI-evaluated patients treated with IV-tPA in a Danish stroke center between 2004 and 2010. Patients with DWI lesions >1/3 of the middle cerebral artery territory were excluded from treatment. The TOAST criteria were used to classify patients into a stroke subtype based on the results of the complete diagnostic work-up available at three months. A favorable 90-day outcome was defined as a modified Rankin Scale score of 0 to 1. Early neurological improvement was defined as complete remission of the neurologic deficit or an improvement of ≥4 on the NIHSS at 24 hours. Multivariable logistic regression analyses were used to compare outcomes among stroke subtypes adjusted for clinical and imaging characteristics.

Results:
A total of 557 patients were analyzed: 202 (36%) had large vessel disease, 153 (27%) had cardioembolic stroke, 109 (20%) had small vessel disease and 93 (17%) were of other or undetermined etiology. A favorable outcome was achieved by 361 (64.8%) patients. Patients with cardioembolic strokes were more likely to achieve a favorable outcome as opposed to large vessel disease patients (adjusted OR, 2.9 (95% confidence interval, 1.1-7.4)). Similarly, the probability of an early neurological improvement was increased in cardioembolic stroke patients in comparison with large vessel disease patients (adjusted OR, 3.5 (95% confidence interval, 1.6-7.6)).

Conclusions:
The ischemic stroke subtype influenced early as well as late clinical outcome after treatment with IV-tPA in MRI-selected patients. Our findings argue for a potentially more successful IV-tPA-induced recanalization in strokes of cardioembolic origin in comparison with large vessel disease strokes.
Abstract W P64: Round the Clock In-house Stroke Neurologist Presence: Impact on Treatment Times for Acute Ischemic Stroke
Authors: Sapkota Biggya L , Sirelkhatim Abdelazim , Dellinger Caryl , Devlin Thomas G ,   Erlanger Southeast Regional Stroke Cntr
Published: July 2021

Background:
We describe a single center experience of 24hours 7days a week In-house attending Stroke neurologist presence starting April 2013, in reducing the delay in treatment of Acute Ischemic Stroke.

Material and Methods:
All consecutive ischemic stroke patients treated with IV alteplase (tissue plasminogen activator [tPA]) were retrospectively and prospectively registered in the stroke registry. In-hospital delays were analyzed as median/mean door-to-needle time (DNT) in minutes for patients receiving iv-tPA for the specified time periods.

Results:
A total of 262 patients were treated with tPA between April 2011 to July 2014. The mean DNT for the period 4/11 to 3/12 was 102 minutes, for 4/12 to3/13 was 67minutes and for 4/13 to current (7/14) was 38 minutes. (63% improvement compared to 2011/12) The DTN time during the ‘working hours’ (8 am to 5pm) as well as ‘out-of-hours’ were improved with significant percentage of patients being treated ‘out-of-hours’. The in hospital mortality, LoS (length of stay) and sICH (symptomatic ICH) were not adversely affected.

Conclusion:
We were able to demonstrate the feasibility of 24/7 in-house attending stroke Neurologist presence and its significant impact in reducing the delay in treatment time of acute ischemic stroke throughout the 24hour period.
Abstract W P73: Inside Intramural Thrombus Formation with Inflammatory Reactions Is Relevant to the Rupture of Cerebral Aneurysms
Authors: Shimoda Yusuke , Nakayama Naoki , Hokari Masaaki , Abumiya Takeo , Shichinohe Hideo , Kazumata Ken , Houkin Kiyohiro
Published: July 2021

Background and Purpose:
Although recent researches on cerebral aneurysms (CAs) have been performed with the hydrodynamic or the molecular biological technique, the mechanisms of rupture are not fully understood. The aim of this study is to assess the mechanism by a comparison between ruptured and un-ruptured CAs with histopathological and electron-microscopic analysis.

Methods:
We analyzed 33 CAs (24 ruptured, 9 un-ruptured) collected surgically after neck clipping. As for the ruptured CAs, we operated them within 24 hours from the onset. HE staining, Elastica Masson staining, PTAH staining, and CD68 immunohistochemical staining were performed with paraffin sections. Morphological analysis with Scanning Electron Microscopy (SEM) was performed with 6 CAs (3 ruptured, 3 un-ruptured).

Results:
The common histopathological finding in both ruptured and un-ruptured CAs was that the aneurysmal wall consisted mostly of thick collagen layer without normal internal elastic lamina and media. The characteristic histopathological finding in ruptured CAs was inside intramural thrombus formation with infiltration of CD68 positive cells at the rupture point. The common SEM finding in both ruptured and un-ruptured CAs was the denudation of endothelial cells and the exposure of a subendothelial amorphous or a fibrous surface. The characteristic SEM finding in ruptured CAs was the cluster formation of thick fibrin fibers with incorporation of macrophages and platelets.

Conclusions:
While the endothelial denudation, the disappearance of internal elastic lamina and media, and the predominance of collagen layer in the aneurysmal wall were common in both ruptured and un-ruptured CAs, inside intramural thrombus formation with inflammatory reactions was characteristic only in ruptured CAs. This result suggests that thrombo-inflammatory reactions in CAs may act as a trigger for ruptures.
Abstract 17: Remote Ischemic Preconditioning Reduces New Vascular Brain Injury early after Carotid Artery Stenting: A Randomized Controlled Trial
Authors: Zhao Wenbo , Ma Chun , Ovbiagele Bruce , Hou Baojun , Sun Yongxin , Feng Wuwei (Wayne) , Meng Ran , Ding Yuchuan , Wu Weijuan , Duan Yunxia , Shi Jingfei , Ji Xunming
Published: July 2021

Introduction:
Cerebral embolization is a major complication of carotid artery stenting (CAS). Remote ischemic preconditioning (RIPC) have been shown to reduce distal embolization in coronary stenting, but it is unclear whether RIPC can reduce embolization after CAS.

Objective:
To evaluate the effect of RIPC on cerebral embolization after CAS

Hypothesis:
We assessed the hypothesis that RIPC can reduce new vascular brain injury early after CAS.

Methods:
189 symptomatic carotid artery stenosis patients treated with CAS, were allocated randomly to RIPC group, control group, and sham RIPC group. All patients received standard background medical therapy. Patients in the RIPC and sham RIPC group underwent RIPC and sham RIPC twice daily respectively. The primary outcome was incidence of new brain parenchymal lesions on MRI at 48hr after CAS. The secondary outcomes were lesion size and occurrence of clinical events within 6 months after CAS. One-way ANOVA, Chi-Square test and Wilcoxon signed-rank test were used accordingly.

Results:
162 patients, who completely finished CAS and MRI, were included in the primary analysis. Incidence of new lesions on post-treatment MRI was 19.23% in the RIPC group, 46.43% in the control group (RR, 0.41; 95% CI 0.22-0.77; p=0.003) and 42.59% in the sham RIPC group (RR, 0.45; 95% CI 0.24-0.85; p=0.009). Median volumes of new lesions and median total lesion volume were both smaller in RIPC group than other 2 groups (p<0.01 each). However, no statistical difference was observed between the groups regarding clinical events.

Conclusions:
RIPC was associated with a significant reduction in the occurrence of new brain parenchymal lesions within 2 days of CAS. These results need to be replicated and future larger studies should be sufficiently powered to examine the effect of RIPC on clinical events after CAS.
Abstract 172: tPA Variant tPA-A296-299 Prevents Impairment of Cerebral Autoregulation After Stroke Through LRP Dependent Increase in cAMP and p38 MAPK
Authors: Armstead William , Riley John , Yarovoi Serge , Higazi Abd Al-Roof , Cines Douglas
Published: July 2021

Introduction:
The sole FDA approved treatment for acute stroke is tissue type plasminogen activator (tPA). However, its brief therapeutic window and post-treatment complications markedly constrain its use. The limited efficacy of tPA may be explained in part by our finding that it potentiates impairment of cerebral autoregulation after stroke in pigs. Upregulation of JNK MAPK after thrombotic stroke contributes to tPA mediated impairment of autoregulation whereas p38 is protective. Vasodilation is mediated by elevation of cAMP. However, cAMP falls after stroke due to over activation of NMDA receptors (NMDA-Rs) by toxic levels of glutamate, which is exacerbated by tPA.

Hypothesis:
Wild type (wt) tPA can bind to either the lipoprotein-related receptor (LRP), which mediates vasodilation, or NMDA-Rs. We propose that wt tPA given after stroke primarily binds to NMDA-Rs, reduces cAMP, which impairs ability of cerebral vessels to vasodilate. tPA-A296-299, a variant that is fibrinolytic but cannot bind to NMDA-Rs, preferentially binds LRP, which increases cAMP and p38 and limits impairment of autoregulation after stroke.

Methods:
Anesthetized pigs equipped with a closed cranial window were used. Stroke was induced by photothrombosis, CBF determined by radiolabeled microspheres, and CSF cAMP and p38 determined by ELISA.

Results:
CBF was unchanged during hypotension (mean arterial pressure decreased by 45%) in sham animals. CBF was reduced in brain tissue surrounding the infarct and was reduced further during hypotension, indicating impairment of autoregulation. Autoregulation was further impaired by wt tPA which was prevented by MK801 and tPA-A296-299. Protection by tPA-A296-299 was blocked by anti LRP Ab, the LRP antagonist RAP, the p38 inhibitor SB 203580, but not by IgG. Stroke reduced CSF cAMP, which was reduced further by wt tPA, but augmented by tPA-A296-299. CSF p38 was unchanged by wt tPA, robustly increased by tPA-A296-299, and decreased by co-administered anti LRP Ab and RAP but not by IgG.

Conclusions:
tPA-A296-299 prevents impairment of cerebral autoregulation after stroke through LRP dependent increase in cAMP and p38.