bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3754: Homocysteine Induces Alternations Of Tight Junction Proteins In Brain Endothelial Cells.
Authors: Tyagi Neetu , Qipshidze Natia , Givvimani Srikanth , Mishra Paras K , Lominadze David , Tyagi Suresh C
Published: July 2021

Hyperhomocysteinmia (HHcy) is associated with neurological disorders (Stroke, Alzheimer, Parkinson etc) and causes blood brain barrier (BBB) dysfunction. We previously showed that an elevated level of homocysteine (Hcy) increased formation of filamentous actin and enhanced endothelial layer permeability. In the present work we tested the hypothesis that Hcy induces oxidative stress and binding to endothelial cells (ECs) alters expression of endothelial tight junction proteins (TJP). In this study mouse brain microvascular endothelial cells (bEND3) were grown in gold plated chambers of an electrical cell-substrate impedance system, 8-well chambered. Confluent bEND3 were treated with different doses of Hcy with mitogen-activated protein kinase (MEK) kinase inhibitors (PD98059 or U0126) or H
2
O
2
(oxidant), or medium alone for 24 h. Reactive oxygen species (ROS) was detected using DCFH-DA assay. Hcy induced a dose-dependent decrease in EC junction integrity as determined by transendothelial electrical resistance (TEER). Our results show that high dose of Hcy induces oxidative stress, which cause down regulation of the TJPs contents occludin, zona occluden-1 (ZO-1), and zona occluden-2 (ZO-2) in bEND3s. Hcy-induced decreases in contents of the TJPs were blocked by PD98059, U0126. While BQ788 inhibited endothelin-1-induced decrease in TEER, it did not affect Hcy-induced decrease in TEER. These data suggest that Hcy increases EC layer permeability via the MEK kinase signaling pathway by affecting TJPs, which are bound to actin filaments. Therefore, increased binding of Hcy with ECs during cerebo-vascular diseases may increase microvascular permeability by altering the content and possibly subcellular localization of endothelial TJPs.
Abstract 3799: Baseline Total Cholesterol Levels and Risk of Developing Brain Edema after Intravenous Thrombolysis in Acute Ischemic Stroke Patients
Authors: Lorenzano Svetlana , Ahmed Niaz , Furie Karen L , Wahlgren Nils , Toni Danilo
Published: July 2021

Objectives:
There is evidence that low plasma cholesterol levels(CLs) are among the factors that contribute to blood brain barrier disruption in acute ischemic stroke, leading to hemorrhagic transformation.The aim of this was to evaluate the association between baseline CLs and the development of brain edema (BE)after i.v. thrombolysis in AIS.

Methods:
We analyzed all the data of AIS patients treated with i.v. rt-PA in Italy from 2003 to 2009 included in the international internet-based SITS-ISTR.The presence and severity of the BE was assessed on 22-36 hour and 7-day neuroimaging as mild, moderate and severe.Total CLs were obtained within 24 hours from symptom onset.Univariate and multivariate analyses were performed.

Results:
Overall, 4194 patients were included,of which 2577/4194 (61.4%) had data on baseline CLs.We analyzed CLs based on quartiles:≤164 mg/dl,≤191 mg/dl,≤221 mg/dl and >221 mg/dl. 1126/3782 (29.8%) developed BE within 22-36 hours of symptom onset,397 of 1015 (39.1%) at 7 days. In 103 cases (25.9%)BE developed between 36 hours and 7 days.Of 1126 patients with both 22-36 hour and 7-day neuroimaging, 89 (7.9%)had a BE worsening and 21 (1.9%)an improvement.Compared to those without BE,patients with BE were more likely to be dependent before stroke (p=0.031),have AF (p<0.0001),have early ischemic signs on baseline CT,higher prevalence of cardioembolic and large vessel mechanism,more SICH per NINDS definition,(p<0.0001).BE+ subjects had higher baseline median NIHSS(17 vs 11,p<0.0001), blood glucose levels (BGLs)(p=0.001) and DBP(p=0.044).Patients with BE had a worse outcome in terms of 3-month mRS>2 (72.5 vs 35.3%) and death (25.8 vs 6.7%) (p<0.0001).Subjects with BE were less likely to have a history of dyslipidemia (p=0.009).Independent predictors of BE developing within 22-36 hours were baseline NIHSS(OR1.104,95%CI 1.085-1.124,p<0.0001), BGLs(OR1.003,95%CI 1.001-1.005, p=0.014), onset-to-door time interval (OR1.002,95%CI 1.000-1.005,p=0.017), early ischemic signs on baseline CT (OR1.797,95%CI 1.127-2.867,p 0.014).NIHSS was confirmed as the strongest independent predictor for the presence of BE at the 7-day neuroimaging and for moderate and severe BE. BGLs was the only independent predictor of BE worsening (OR1.007,95%CI 1.000-1.014,p=0.05).Lower baseline CLs, in particular values <164 mg/dl,were independent predictors of BE improvement (OR3.758,95%IC 1.299-10.869,p=0.015)whereas higher values (>221 mg/dl) were independent predictors of severe BE at the 7-day neuroimaging (OR2.020,95%CI 1.044-3.94,p=0.037).

Conclusions:
Our study did not show an independent association between lower baseline total CLs and the risk of BE developing after i.v. thrombolysis in AIS. More studies are necessary to address this issue, particularly considering also the LDL-CLs and the use of statins at stroke onset and during the hospital stay.
Abstract 3829: Extraluminal Protruding Plaques in Intracranial Arteries. An angiographic and pathological analysis of Circle of Willis specimens from the Nun Study
Authors: Suri M Fareed K , Majidi Shahram , Meints Joyce , Divani Afshin A , Qureshi Adnan I
Published: July 2021

BACKGROUND
There is little data about extraluminal protruding plaques in intracranial arteries. Such plaques may not cause luminal stenosis and may be undetectable by standard angiographic modalities. It is important to identify the prevalence of such plaques because these plaques may be a cause of thrombosis and ischemic events in patients with cryptogenic strokes.

OBJECTIVE
To identify the prevalence of extraluminal protruding plaques in intracranial arteries from autopsy specimens of Nun Study.

METHODS
A random sample of 54 specimens was selected from Nun Study repository of post-mortem intracranial arteries (Circle of Willis). The Nun Study is a longitudinal study of aging and Alzheimer's disease funded by the National Institute on Aging including 678 participants who are 75 to 106 years of age. Basilar artery and proximal middle cerebral arteries were inspected and arteries with plaques were identified. The specimens were placed in a liquid container and an angiographic catheter was placed in vessel of interest. Using iodinated contrast media and Ziehm Vista C-arm, angiography was obtained in multiple planes. Percentage luminal stenosis was measured using normal proximal or distal segment of the vessel as reference. Using microscopic images, extraluminal protruding plaques was then sequentially measured. Percentage increase in extraluminal wall diameter was calculated as (extraluminal diameter at plaque site - normal diameter)/normal diameter x100.

RESULTS
Out of 162 samples, plaques were identified in 126 samples. The characteristics of the plaques are tabulated. The percentage increase in extraluminal wall diameter was 10.33 ± 8.13. For vessel with angiographically occult plaques, the percentage increase in extraluminal wall diameter was 9.2±3.2. In extraluminal protruding plaques, the median protrusion was 0.3 mm and maximum protrusion was 0.9 mm. There was no difference between the percentage extraluminal protrusion between the middle cerebral (0.3±0.1) and basilar artery plaques (0.36±0.2), p=0.8. The frequency of extraluminal plaques without angiographic stenosis of any severity was higher than extraluminal plaques with angiographic stenosis (52% and 56% for middle cerebral artery and basilar artery, respectively).

CONCLUSIONS
There appears to be a high prevalence of extraluminal protruding plaques among elderly persons and most of these plaques are not detected by angiography. Newer, imaging modalities like vessel wall high resolution visusalization by magnetic resonance imaging may help identify the prevalencc and ischemic event risk associated with such plaques.
Abstract 3837: Vascular Risk Profiles and Cognitive Impairment in a 20-year Follow-up of Three Ethnic Groups: the Southall and Brent REvisited (SABRE) Cohort
Authors: Stewart Robert , Tillin Therese , Chaturvedi Nish
Published: July 2021

Introduction:
There is substantial ethnic variation in vascular risk profiles and their outcomes. For example, stroke risk is raised by 50-100% in Black and South Asian compared to White UK residents but is more strongly associated with diabetes than hypertension in the former two groups. Associations with cognitive outcomes have not been previously compared.

Hypothesis:
Mid-life hypertension and diabetes will be more strongly associated with later life cognitive impairment in Black and South Asian compared to White residents.

Methods:
SABRE is a UK community based tri-ethnic (White, Black and South Asian) cohort of male and female London residents aged 40-69 years at baseline (1988-1990), and 58-86 years at follow up (2008-2011). Hypertension at baseline (resting blood pressure >140/90 or antihypertensive treatment) and diabetes at either exam were investigated in relation to cognitive impairment at follow-up. Cognitive impairment was ascertained as the lowest 10% of averaged z-scores calculated separately within the 3 ethnic groups for 9 tests: immediate and delayed word list recall, digit span forwards and backwards, verbal fluency, Color Trailmaking Tests A and B, delayed visual recall and the Community Screening Instrument for Dementia. Age, gender and years of education were entered as covariates.

Results:
Prospective data were analysed on 570 White, 432 South Asian and 185 Black residents. Baseline hypertension prevalences in these three groups were 14.8%, 27.1% and 37.2% respectively and diabetes prevalences were 19.5%, 43.4% and 41.3% respectively. Hypertension (p=0.005) and diabetes (p=0.029) were associated with follow-up cognitive impairment after full adjustment. On stratifying by ethnic group, no significant associations were found in White participants, hypertension was only associated with cognitive impairment in South Asians and diabetes only in Black participants. Hypertension and diabetes in combination were associated with cognitive impairment to a similar extent in both South Asian and Black participants, but not in Europeans.

Conclusion:
Vascular risk factors vary in their impact on cognitive impairment between ethnic groups which may reflect underlying differences in risk profiles and modification of their impact on end-organ damage. Multi-ethnic cohorts present a valuable opportunity for investigating more heterogeneous risk profiles and better clarifying mechanisms underlying the impact of individual risk factors.
Abstract 3858: Evaluation of Serial Neuroimaging in Patients with Intracerebral Hemorrhage
Authors: Shams Tanzila , Mehndiratta Prachi , Termsarasab Pichet , Masoud Hesham , Sehgal Siddharth , Sila Cathy
Published: July 2021

Introduction:
The availability of sophisticated neuroimaging has led to increased utilization of imaging studies, particularly at comprehensive stroke centers. This increase in advanced imaging contributes to healthcare costs and has been questioned in this era of reducing reimbursement.

Hypothesis:
Multiple neuroimaging studies have limited impact in determining the plan of care for most patients with intracerebral hemorrhage.

Methods:
An IRB-approved retrospective chart review of all patients with Intracerebral Hemorrhage (ICH, ICD 431) treated at UH-CMC in 2010 collected data on demographics, number of neuroimaging studies and imaging characteristics, and the impact of testing on determining a medical or surgical plan of care. Hemorrhage location dictated one of two groups: basal ganglia and thalamus (BG) versus IVH alone, infratentorial and lobar (NBG).

Results:
Data was available on 120 (86%) of patients; 74 (62%) were male. Mean volume of ICH on initial CT was significantly smaller at 8.5±11.7cc in 41 BG patients vs 63±27cc in 79 NBG patients (p=0.01). The decision to pursue surgical treatment (extraventricular drainage in 14, craniotomy in 9, or both in 4) was determined prior to a third neuroimaging study. Three or more neuroimaging studies were obtained in 56% of BG and 59% of NBG patients. Hematoma expansion was less likely to occur in BG vs NBG patients, both for significant hematoma expansion (>33% or +12.5cc increase, 5% vs 22%, p=0.05) and nonsignificant hematoma expansion (10-33% increase, 2.4% vs 8.9%, p=0.27). Hematoma expansion was exclusively within the first 2 imaging studies for BG patients but occurred in a delayed fashion in 3 (4%) of NBG patients. MRI was obtained in 17% of BG and 44% of NBG patients; only in 3 of the NBG patients did it identify a vascular malformation which led to surgery in 1 patient.

Conclusion:
Although more than half of patients with intracerebral hemorrhage underwent three or more neuroimaging studies, 95% of patients’ care plan decisions were determined by the first, and to a lesser extent, the second neuroimaging study. Serial neuroimaging after the second study was of no value in patients with small basal ganglia hemorrhages and impacted the care plan in less than 10% of patients with hemorrhages in alternate locations. Our data suggests many neuroimaging studies can be safely omitted.
Abstract 3888: Use of Electronic Triggers to Insure Compliance with Nursing Driven Stroke Measures
Authors: MARCOTTE Elizabeth J , Barrett Coletta C
Published: July 2021

Background and Purpose:
Our Lady of the Lake Regional Medical Center is the largest hospital in Louisiana with 734 Bed licensed beds. Patient care in the adult care units is delivered by over 1200 nurses in 20 acute care units and 5 intensive care units. There are over 25,000 Inpatient discharges from the medical center annually. Stroke discharges for the fiscal year 2010 were 867. The Medical Center utilizes an electronic medical record and is supported by a health system department that drives the development and oversight for the IT implementation in the 4 hospitals within our system. With only 5 Certified Stroke Centers in Louisiana, none in our geographic region; OLOL set a goal to become stroke center certified. With competing priorities and multiple quality initiatives in the medical center and across our health system, OLOL was challenged to develop processes to insure compliance in meeting the nursing driven stroke measures; dysphagia screen and stroke patient education. Our task was to develop electronic triggers to insure that screenings and education occurred at the appropriate time during the patient stay.

Methods:
This effort required work across disciplines and the health system. Our caregivers (nurses, physicians, and pharmacists), quality leaders, technology team members, and process experts worked together to reach our collective goal. The team developed triggers, or tasks required to be completed, based on an admission diagnosis or suspected diagnosis of stroke. When completing either task, the electronic record would auto populate a specific form for the task to be completed. For stroke education, the electronic form navigates the nurse through the 5 required components of stroke education, allowing the nurse to print a hardcopy of the required education for patient review. For the dysphagia screen, the auto form directs the nurse how to complete the task and automatically implements orders based on a pass or fail of the screen.

Results:
Data collected from Get with the Guidelines, Stroke at our organization pre and post implementation of the triggers were measured. Compliance with dysphagia screen increased from 59% to 87%. Stroke education increased from 0% to 94.9%.

Conclusion:
Electronic triggers improved compliance with meeting nursing driven stroke measures for patient education and dysphagia screen. The need to provide quality stroke care and improvement efforts for documentation was identified as a need before the application for Stroke Center Certification. Stroke meaningful use requirements for stimulus dollars helped to provide the organizational focus of resources that otherwise might not have appropriated for Stroke.
Abstract 3898: Predictors Of Admissions In Patients Presenting To Emergency Department With Transient Ischemic Attacks In United States- A National Survey
Authors: Tariq Nauman , Chaudhry Saqib A , Rizvi Ashter , Suri M Fareed K , Rodriguez Gustavo J , Qureshi Adnan I
Published: July 2021

Background:
The estimates of patients who present with transient ischemic attacks (TIA) in the emergency departments (ED) of United states and their disposition including factors that determine hospital admission are not well understood.

Objective:
We used a nationally representative database to determine the rate and predictors of admission in TIA patients presenting to the ED.

Methods:
We analyzed the data from National Emergency Department Sample (NEDS 2006-2007) for all patients presenting with primary diagnosis of TIAs in the United States. Samples were weighted to provide national estimates of TIA hospitalizations and identify factors that increase the odds of hospital admission including age, sex, type of insurance, hospital type (urban teaching, urban nonteaching and non urban). Multivariate logistic regression analysis was used to identify predictors of hospital admission.

Results:
Of the total of 631750 patients presenting with TIA to the EDs in a period of two years in US, 41, 9447 (66.4%) were admitted to the hospital. In the multivariate analysis, independent factors associated with hospital admissions were women (odds ratio[OR] 1.042, 95% confidence interval [CI] 1.014-1.071, p =0.003) , Medicare insurance type (OR 0.82, 95% CI 0.88-0.93, p<0.0001), and urban non-teaching hospital ED (OR 0.825, 95% CI 0.778-0.875, p<0.0001).

Conclusion:
Approximately 70% of all patients presenting with TIAs to the EDs within United States are admitted. Factors unrelated to patients condition such as insurance status and ED affiliated hospital type play an important role in the decision to admit TIA patients to the hospitals.
Abstract 3918: Use of Data Timeline as Tool for Improved Door-to-Needle Times
Authors: Falk Diane B , Hodges Wayne
Published: July 2021

Background and Issues:
NIH - NINDS have benchmarked time targets for use of Activase (tPA) for potential thrombolysis in patients triaged as an AIS with a door to needle (DTN) time of 60 minutes or less. It has been reported that the most referenced challenges faced in ED and Stroke Centers involves balancing time urgency with synching of key diagnostics within the hospital. The Joint Commission (JC) recommends that quality data collected also be shared with involved inter-disciplinary team members. This data is required to JC on a quarterly basis, but there is not a recommended method of using the data internally.

Purpose:
The purpose of the program improvement initiative was 1.) decrease the DTN time to less than 60 minutes in at least or greater than 50% of all patients receiving tPA and 2.) develop a method that shares program quality points internally with all disciplines, department leaders and front-line staff, with a model that simplifies reporting, increases report turn-around time and engages staff in processs improvement.

Methods:
In 2008, it was noted that door to needle times for tPA cases were increasing, and the rate of administration was decreasing. Various report formats were developed in a means to supply the data points to stake holders, with limited success. In 2009, a new reporting tool was configured to present individual DTN timelines for each tPA patient, and then distributed to the Inter-disciplinary Stroke Performance Improvement Committee within 48 hours.

Results:
The multidisciplinary nature of stroke care requires interaction and coordination of all members of the team to meet time sensitive performance measures. But the collection of data and disseminating that data in formal, infrequent committee meetings with department leaders does not directly result in program improvement. By developing a tool that highlights critical timeline benchmarks and then promptly distribute team-wide, performance outliers were identified in nearly real-time and addressed effectively. A second result is that each department made efforts to avoid being noted as a “breakdown” point. Some departments reported the development of a competitive approach within the department to post the “best times”. This process resulted in marked improvement in compliance with the 60 minutes DTN time, and may have resulted in more aggressive approach to using tPA, as evidenced by increase rate of treatment.

Conclusions:
The rapid collection and distribution of individual patient timeline data has proven to be a quantifiable benefit with an increased thrombolytic administration percentage, with concomitant decrease in door-to-needle time. In addition, internally sharing information has resulted in an improved department as well as individual staff investment in stroke patient care and program improvement.
Abstract 3920: Epilepsy as a Long-Term Complication After Cerebral Venous Thrombosis
Authors: Cantu-Brito Carlos , Chiquete Erwin , Arauz Antonio , Merloz-Benitez Marlon
Published: July 2021

Background.
Seizures is a very common clinical presentation of cerebral venous thrombosis (CVT); however, little is known about the future risk of epilepsy in patients suffering CVT. Our objective was to analyze risk factors for epilepsy in a long-term follow-up after CVT.

Methods.
This is a cohort descriptive study of consecutive non-selected patients with acute cerebrovascular disease, systematically registered from 1986 to 2010 in a third-level referral center of Mexico City. Here we analyzed 340 patients who survived the first 6 months after CVT, who were not epileptic at baseline and for whom complete long-term information on neurological outcome was available.

Results.
Seizures occurred in 183 (54%) patients, in 26% of them as a clinical presentation and 74% at some point during follow-up. Focal motor seizures occurred in 6.5%, secondary generalized focal seizures in 13.8% and generalized tonic-clonic seizures in 22.4%. Status epilepticus occurred in 13 (7%) cases. In all, during a median follow-up of 28 months (range 2 to 288 months), epilepsy was present in 14.7% (27.3% of those who presented seizures). In a multivariate analysis adjusted for multiple confounders, risk factors associated with an increased risk of epilepsy during follow-up were presenting seizures as a clinical presentation [odds ratio (OR): 4.32, 95% confidence interval (CI): 2.20-8.48], pregnancy and puerperium (OR: 2.03, 95% CI: 1.11-3.71) and thrombosis of the longitudinal sinus (OR: 1.86, 95% CI: 1.01-3.41).

Conclusion.
Seizures are common at CVT presentation, but risk increases during the acute phase after thrombotic event. Most seizures resolve during the first month, but epilepsy occurred in 15% of patients with CVT in the long run.
Abstract 3962: Hematopoietic Endothelial Progenitor Cells Enhance Motor Function And Motor Map Integrity Following Cerebral Ischemia.
Authors: Mocco J , Afzal Aqeela , Thomas Nagheme , Warraich Zuha , Kleim Jeffery
Published: July 2021

Stroke is the leading cause of disability in the Unites States resulting in upper extremity motor impairments. The present study examined the efficacy of systemically administered hematopoietic endothelial progenitor cells (EPCs) for ameliorating motor impairments and cortical dysfunction following cerebral ischemia.

Methods:
Baseline motor performance of Forty one male adult rats was established on a single pellet reaching task. Animals were assigned to one of five experimental conditions that counterbalanced baseline motor performance. Animals in the Stroke condition (n=7) received infusion of endothelin-1 onto the middle cerebral artery contralateral to the preferred paw. Animals in the PRE (n=7) and POST (n=7) conditions received the same infusion of endothelin-1 one but also received ten million EPCs injected into the tail vein either thirty minutes before (PRE) or immediately after (POST) infusion. The EPC’s were enriched from the bone marrow of a separate group of donor rats using nanoparticles tagged with LIN negative and CD90 markers. SHAM (n=9) animals only received EPC infusion and CONTROLS received no stroke or EPC infusion. One, three and five weeks following stroke all animals were tested on the skilled reaching task after which intracortical microstimulation was used to derive maps of forelimb movement representations within the motor cortex contralateral to the preferred paw. All assessments were performed in a blinded manner.

Results:
showed POST animals performed significantly better on single pellet reaching than animals in all other stroke conditions on weeks 3 and 5. Control animals scored a reaching accuracy of 41±8.1% and 46±11% at 3 and 5 weeks, respectively. Stroke decreased this task to 12±2.1% and 18±2.8%, respectively (p<0.05, compared to controls at both time points). Injection of EPC’s following reperfusion led to an increase in reaching accuracy to 27±2.6% and 32±2.4%, at 3 and 5 weeks, respectively (p<0.05, compared to stroked non-EPC cohort at 5 weeks). Further, POST animals had significantly larger forelimb motor maps than animals in all other stroke conditions. Infarct size did not significantly differ between the stroke conditions. The results show that post stroke treatment of EPCs does not reduce infarct size but does enhance the functional integrity of residual cortical tissue that in turn supports enhanced behavioral outcome.
Abstract 41: Acute Seizures and Neurologic Deficits Predict Epilepsy After Pediatric Stroke
Authors: Fox Christine K , Glass Hannah C , Johnston S. Claiborne , Sidney Stephen , Nguyen-Huynh Mai N , Fullerton Heather J
Published: July 2021

Background:
Epilepsy may be frequent after pediatric stroke. However, current incidence estimates are from tertiary referral centers and vary widely, and little is known about its risk factors.

Methods:
We performed a population-based study of epilepsy within a cohort of children with stroke (birth-20 years) enrolled in a Northern California integrated health care system, from January 1993 through December 2007, to determine epilepsy incidence rates and predictors. Children with symptomatic ischemic and hemorrhagic stroke surviving to hospital discharge were included in the analysis. Seizures were identified using clinical databases, and epilepsy diagnoses were confirmed by independent record review by two neurologists with arbitration by a third. Based on International League Against Epilepsy proposed guidelines, epilepsy was defined as a confirmed unprovoked seizure > 30 days after stroke. Survival analysis was used to determine rates and predictors of epilepsy after stroke. Using multivariable analysis, hazard ratios (HR) were adjusted for gender, age (neonatal versus later childhood), stroke subtype (ischemic versus hemorrhagic), outcome at hospital discharge, and acute seizures at the time of stroke.

Results:
From an initial study population of 2.4 million children, 371 children with stroke were included. Of these, 110 cases were neonatal and 261 were later childhood; 226 were ischemic and 145 were hemorrhagic. At stroke ictus, 36% had an acute seizure, and 66% had a neurologic deficit at hospital discharge. Median length of follow-up was 4.5 years (IQR 1.9-8.6). Post-stroke epilepsy occurred in 89 subjects. The average annual incidence rate of epilepsy was 6.4% (95% CI 5.2%, 8%), with a 5-year cumulative risk of 25% (95% CI 20%, 30%) and 10 year cumulative risk of 40% (95% CI 32%, 51%) (
Figure
). Predictors of epilepsy included neurologic deficit at hospital discharge (HR 1.8, 95% CI 1.07-3) and seizure at stroke ictus (HR 4.1, 95% CI 2.6-6.5) (
Figure
), but not gender, age or stroke subtype.

Conclusions:
Epilepsy is common after stroke in children. Those with seizures at onset of stroke are at particularly high risk, in keeping with animal models of epileptogenesis and recent studies of human neonatal hypoxic ischemic brain injury. Future studies are needed to further identify children at greatest risk for post-stroke epilepsy.

Figure.

Kaplan Meier curves of (A) seizure free survival after pediatric stroke, (B) among children with or without neurologic deficit, and (C) among children with our without seizure at the time of stroke.
Abstract 58: The Iscore Predicts Efficacy Of Thrombolytic Therapy For Acute Ischemic Stroke
Authors: Saposnik Gustavo , Fang Jiming , Kapral Moira , Tu Jack , Mamdani Muhammad , Austin Peter , Johnston Claiborn S ,   on behalf of the Investigators of the Registry ofthe Canadian Stroke Network and,   the Stroke Outcomes Rsch Canada (SORCan) Working group
Published: July 2021

Background:
The iScore is a validated tool developed to estimate the risk of death and functional outcomes early after an acute ischemic stroke. It includes demographics, stroke severity and subtype, vascular risk factors, cancer, renal failure, and pre-admission functional status. Limited information is available to predict the clinical response after intravenous thrombolytic therapy (tPA).

Objective:
To determine the ability of the iScore to predict the clinical response and risk of hemorrhagic transformation after tPA.

Methods:
We applied the iScore (
www.sorcan.ca/iscore
) to patients presenting with an acute ischemic stroke at 11 stroke centres in Ontario, Canada, between 2003 and 2008, identified from the Registry of the Canadian Stroke Network (RCSN). We compared outcomes between patients receiving and not receiving tPA adjusting for differences in baseline characteristics through matching by propensity scores. Three groups were defined a priori as per the iScore (low risk 180).

Outcome Measures:
Poor outcome, the primary outcome measure, was defined as disability at discharge or death at 30 days. Secondary outcomes included disability at discharge, neurological deterioration and intracranial hemorrhage (any type and symptomatic).

Results:
Among 12,686 patients with an acute ischemic stroke, 1696 (13.4%) received intravenous thrombolysis. Overall, 589 tPA patients were matched with 589 non-tPA patients (low iScore risk), 682 tPA were matched with 682 non-tPA patients (medium iScore risk) and 419 tPA patients were matched with 419 non-tPA patients (high iScore risk). There was good matching in all three groups. Higher iScore was associated with poor functional outcome in both the tPA and non-tPA groups (p<0.001). Among those with low and medium iScore risk, tPA use was associated with lower risk of poor outcome (Low iScore RR 0.74; 95%CI 0.67-0.84; medium iScore RR 0.88; 95%CI 0.84-0.93). There was no difference in clinical outcomes between matched patients receiving and not receiving tPA in the highest iScore group (RR 0.97; 95%CI 0.94-1.01). Similar results were observed for disability at discharge and length of stay. The incident risk of neurological deterioration and hemorrhagic transformation (any or symptomatic) increased with the iScore risk (
Figure
).

Conclusion:
The iScore appears to predict clinical response and risk of hemorrhagic complications after tPA for an acute ischemic stroke. Patients with high iScores may not benefit from tPA and have higher risk of hemorrhagic transformation, though this finding should be validated independently (underway) before clinical use.
Abstract 77: Beyond TIMI: Recanalization and Reperfusion with Endovascular Thrombectomy for Acute Ischemic Stroke in Multi MERCI
Authors: Liebeskind David S , Walker Gary , Xiang Bin , Nogueira Raul G ,   for the Multi MERCI Investigators
Published: July 2021

Background:
Angiographic definitions for revascularization of arterial occlusion often vary in endovascular stroke trials. Thrombolysis in Myocardial Ischemia (TIMI) scores continue to be used despite inconsistent methods and limited correlation with clinical outcome after stroke. Novel recanalization and reperfusion scores, including the Arterial Occlusive Lesion (AOL) and Thrombolysis in Cerebral Infarction (TICI) scales respectively, have been advanced with limited data on scale metrics. We conducted a prospective analysis of central core lab angiography scores with local site reads in Multi MERCI to establish AOL and TICI metrics of recanalization and reperfusion, linking revascularization with clinical outcomes.

Methods:
Core lab AOL and TICI scores of two central readers were compared and analyzed with respect to local TIMI grade in Multi MERCI (n=164). In Multi MERCI, a modified TIMI was used, where the final TIMI score was the lowest of the TIMI scores in target vessel and the downstream vasculature. Recanalization and reperfusion were analyzed with respect to baseline clinical variables and 90-day outcomes.

Results:
Local site TIMI score showed only modest, but statistically significant correlation with AOL recanalization (0.50, p<0.001) and TICI reperfusion (0.65, p<0.001). Inter-rater reliabilities of central readers were excellent for AOL (κ=0.987) and TICI (κ=0.826). AOL and TICI were moderately correlated (0.83, p<0.001). AOL recanalization was associated with time from symptom onset to procedure (-0.23, p=0.005), platelet count (0.16, p=0.043) and SBP < 150 (0.18, p=0.022). TICI reperfusion was also associated with time from symptom onset to procedure (-0.17, p=0.029), current smoking (0.17, p=0.042), CHF (-0.18, p=0.031) and SBP < 150 (0.20, p=0.013). Across all grades, TICI reperfusion was inversely associated with 90-day death (-0.22, p=0.007) and positively associated with good outcomes (0.24, p=0.003). AOL recanalization showed the same trend, though the association was weaker (-0.12, p=0.129; 0.16, p=0.047). TICI 2b/3 strongly predicted 90-day mRS 0-2 (OR 2.73, p=0.004) and decreased mortality (OR 0.29, p<0.001) beyond AOL 2/3 (OR 2.78, p=0.020; 0.56, p=0.125). AOL and TICI exhibited similar relationships across various sites of arterial occlusion.

Conclusions:
AOL recanalization and TICI reperfusion core lab readings in Multi MERCI revealed excellent reliability and strong predictive value for 90-day clinical outcomes. AOL and TICI scores may discriminate recanalization from reperfusion, allowing further consideration of these distinct aspects of revascularization in future trials.
Abstract 94: Patient Selection using CT Perfusion (CTP) Imaging Improves Effectiveness of Stroke Thrombolysis in the 0-4.5 Hour Time Window
Authors: Manawadu Dulka , Bodla Shankranand , Sztriha Laszlo , Jarosz Josef , Kalra Lalit
Published: July 2021

Background:
The role of CT perfusion (CTP) in thrombolysis decisions remains controversial and there are no studies that compare outcomes of thrombolysis in patients with or without mismatch on CT perfusion imaging.

Methods:
We analysed registry data between Jan 2009 and December 2010 for patients thrombolysed within 0-4.5 hours of stroke onset in whom CTP studies were performed prior to thrombolysis. The centre followed thrombolysis guidelines but patients >80 years were included. CTP was not obligatory in the treatment protocol and failure to demonstrate a mismatch was not a contraindication to thrombolysis. We retrospectively analysed data for estimated CTP mismatch of ≥ 100% according to pre-defined criteria and compared outcomes of thrombolysed patients showing perfusion mismatch with those showing no mismatch.

Findings:
The sample included 160 patients aged between 32-95 years of whom 63 had no mismatch and 97 had a significant mismatch. The two groups were comparable for mean age (73 v 70 years, p=0.18), sex (49% v 54% male, p=0.75), premorbid Rankin Score (mRS) 0-2 (81% v 92%, p=0.77), vascular risk factors profile, mean baseline BP (148/87 v 148/79 mm Hg, p=0.92), mean blood glucose (6.6 v 6.6 mmols/L, p=0.98) and mean National Institute of Health Stroke Scale (NIHSS) score (14.0 v 12.6,p=0.12). Patients who had mismatch prior to thrombolysis showed lower mean 24 hour NIHSS score (7.6 v 11.8, p=0.002) and greater mean 24 hour improvement in NIHSS score (5.1 v 2.0, p=0.010). A higher proportion of patients with mismatch achieved mRS 0-1 and mRS 0-2 at 3 months (36% v 18%, p= 0.012 and 51% v 32%, p=0.015 respectively) but there were no differences in symptomatic sICH rates (1.1% v 0%). Mortality (29% v 18%) and any intracranial haemorrhages (19% v 13%) were lower in mismatch patients but did not achieve significance. Regression analyses showed that PCT mismatch prior to thrombolysis was an independent predictor of both early improvement and functional outcomes at 3 months.

Conclusion:
Stroke patients who have perfusion mismatch on CTP imaging prior to thrombolysis within the 4.5 hour time window show better early and 3 month outcomes compared with those in whom mismatch cannot be demonstrated. Patient selection using multimodal CT may improve the effectiveness of thrombolysis.
Abstract 98: Higher Volume Endovascular Stroke Centers Have Decreased Times to Treatment
Authors: Gupta Rishi , Horev Anat , Nguyen Thanh N , Gershon Raphael Y , Gandhi Dheeraj , Wisco Dolora , Miller Brenda , Tayal Ashis H , Ludwig Bryan , Hussain Muhammad S , Terry John , Jovin Tudor G , Belagaje Samir R , Cronin Carolyn , Tian Melissa , Anderson Aaron M , Frankel Michael , Sheth Kevin N , Liebeskind David S , Nogueira Raul G
Published: July 2021

Background:
Currently, no metric exists for door to arterial puncture time for endovascular treatment in acute ischemic stroke. The aim of this study was to determine the timings of each step of endovascular stroke intervention stratified by the volume of procedures at each center.

Methods:
We retrospectively reviewed patients from seven institutions undergoing endovascular reperfusion therapies for acute ischemic stroke. Patients with anterior circulation strokes treated less than 8 hours from symptoms onset were included. Demographic, radiographic, angiographic and clinical outcomes were collected. The time interval at each milestone from CT acquisition to reperfusion was recorded. Successful reperfusion was defined as achieving a TICI 2B or 3 score as graded by the operator. Symptomatic hemorrhage was defined as a parenchymal hemorrhage type 2 as defined by ECASScriteria. Centers that performed more than 50 intra-arterial stroke interventions annually were considered high volume (HV) centers. A univariate analysis was performed with the Fisher’s exact test for categorical variables and students t-test for continuous variables to compare HV to lower volume (LV) centers. Variables with a p-value < 0.20 were placed in a binary logistic regression model to determine if there were differences in time to treatment between the two groups.

Results:
A total of 338 patients with a mean age of 67±14 years and mean NIHSS of 18±5 were included. The mean time from CT imaging to groin puncture was 108±73 minutes. The mean time from groin puncture to the placement of a microcatheter in the thrombus was 41±21 minutes and total procedure time 104±55 minutes. There were no differences in demographics, site of vascular occlusion and hemorrhage rates between high volume and lower volume centers. In univariate analysis, HV centers had a lower time from CT imaging to groin puncture (89±57 minutes vs. 154±84 minutes, p<0.001), procedure time (93±46 minutes vs. 129±65 minutes, p<0.001), final infarct volume (79±82 cm
3
vs. 94±106 cm
3
, p<0.03) and higher reperfusion rates (73% vs. 59%, p<0.01). In binary logistic regression modeling HV centers were found to have a shorter CT acquisition to arterial puncture time [OR 0.991, 95%CI (0.986-0.996), p<0.001] and higher reperfusion rates [OR 1.79, 95% CI (1.04-3.12), p<0.03].

Conclusions:
Currently there is variability in the time from CT to arterial puncture and total procedure time across institutions, but HV centers appear to have lower times to treatment. Further study is required to determine how to reduce times to treatment and develop a metric for centers to target.
Abstract NS 7: Code 1 (Acute Stroke Response Team): Improving Patient Outcomes Utilizing Simulation Training
Authors: Poole Karen , Filomena Patricia
Published: July 2021

The use of innovative blended learning for stroke program training has enabled the Washington Hospital Center’s Stroke Program in Washington, D.C. to decrease their patient “door presentation time” to Tissue Plasminogen Activator (tPA) “needle time” by 30minutes. Stroke programs always seem to be in a constant state of performance improvement and looking for way s to create seamless care from admission to treatment. A review of stroke response times and needs assessment in 2008 led the MedStar Health Washington Hospital Center Stroke Coordinator to collaborate with MedStar Health Simulation and Training Environmental Lab (SiTEL) to develop team training and individual stroke nurse responder training that includes both online modules and clinical simulation scenarios. Over the past three years this program has evolved and now includes online modules on stroke diagnosis and treatment, didactic instruction, preceptorship with an experienced stroke nurse responder and the use of clinical scenarios with live actors as patients to give nurses and the rest of the team practice with running a stroke code.

Initial objectives/goals included testing the team that had been trained and developing practice and validation scenarios for the nurse stroke responders so they could practice how to assess potential stroke victims, carrying out the stroke protocol and administer tPA. A second scenario is conducted quarterly for the entire team and is used to evaluate the entire process. Throughout this immersive simulation the team of physicians, nurses and radiology technicians must make crucial assessments, critical treatment decisions, follow a stroke protocol, transport the patient, administer tPA, monitor the patient and escalate care as complications arise. This scenario is timed and videotaped to allow the team to debrief after the scenario and review decisions made and actions taken thus increasing their efficiency and effectiveness of critical decision making regarding patient care. The overall success of this education program can be seen in the shortened door to tPA administration time for the acute stroke patient.
Abstract 117: Apolipoprotein E and use of Statins in Intracerebral Hemorrhage
Authors: Woo Daniel , Deka Ranjan , Woo Jessica G , Martini Sharyl , Flaherty Matthew , Haverbusch Mary , Sauerbeck Laura , Martin Lisa , Moomaw Charles J , Kleindorfer Dawn , Kissela Brett , Broderick Joseph P
Published: July 2021

Background:
Apolipoprotein E (ApoE) genotypes have been associated with lobar intracerebral hemorrhage (ICH), and HMG-CoA Reductase Inhibitors (statins) were associated with risk of ICH in a secondary prevention trial. Yet, large meta-analyses of statin use have not consistently identified an increased risk of ICH with statin use. We evaluated whether ApoE genotypes were differentially associated with ICH risk according to statin use.

Methods:
The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study is a prospective ICH study which recruits cases and controls from the same population. Study physicians adjudicated cases and determined ICH location. Subjects were classified as normocholesterolemia (NC), hypercholesterolemia without statin (HC-NS), and hypercholesterolemia with statin use (HC-S) based on chart review. Genotyping for ApoE (
rs429358
and rs7412) was performed using standard methods. Statistical comparisons were performed using Fisher’s exact test and Mantel-Haenszel tests for homogeneity.

Results:
From 1997-2008, the study recruited 597 cases of ICH and 1,548 controls. Of these, 26 cases/ 8 controls were excluded for unknown history of hypercholesterolemia, and 13 cases/ 96 controls were excluded for missing ApoE result. Of the 554 cases included, 204 were lobar in location. For non-lobar ICH cases, no significant differences were observed in ApoE genotype and statin use between NC, HC-NS and HC-S cases and controls. However, for lobar ICH, a marked increased risk of ICH was seen in HC-S patients with Apo E4/E4 (OR=4.5; 95% CI 1.3-16; p=0.02) and E2/E4 (OR=11.3; 95%CI 2.0-64; p=0.005), and there was a trend for Apo E2/E3 (OR=2.8; 95% CI 1.1-7.5, p=0.06) compared with Apo E3/E3. Apo E4/E4 did not demonstrate an increased odds of ICH without statin use (OR=1.6; 95% CI 0.27-9.4; p=0.63). The p-value for heterogeneity of odds ratios did not reach statistical significance between the HC-NS vs. HC-S group.

Conclusion:
Our data support a gene-by-drug effect for lobar ICH and, if confirmed, may indicate a utility for ApoE genotyping to identify patients who would bear the highest risk of ICH with statin use. However, further study is required to determine if an interaction exists or if the finding is associative.
Abstract 123: Effects Of High-frequency RTMS Applied Over Bilateral Leg Motor Areas Using A Double Cone Coil On Walking Function In Post-stroke Patients
Authors: Kakuda Wataru , Abo Masahiro , Momosaki Ryo
Published: July 2021

Objective:
It is difficult to stimulate leg motor areas with magnetic current using a figure-of-eight coil due to the deep anatomical location of the areas. However, a double cone coil is useful for stimulating deep brain regions. We postulated that the use of the same coil may allow repetitive transcranial magnetic stimulation (rTMS) to modulate the neural activity of the same areas. The purpose of this study is to investigate the effect of high-frequency rTMS applied over bilateral leg motor areas with a double cone coil on walking function after stroke.

Materials and methods:
Eighteen post-stroke hemiparetic patients with gait disturbances attended two experimental sessions with more than 24 hours apart, in a cross-over, double-blind paradigm. In one session, high-frequency rTMS of 10 Hz was applied over the leg motor area bilaterally in a 10-sec train using a double cone coil for 20 minutes (total 2,000 pulses). In the other session, sham stimulation was applied for 20 minutes at the same site. To assess walking function, walking velocity and Physiological Cost Index (PCI) were evaluated serially before, immediately after, and 10 and 20 minutes after each intervention.

Results:
The walking velocity was significantly higher for 20 minutes after stimulation in the high-frequency rTMS group than the sham group. PCI was lower in the high-frequency rTMS group than the sham group, but this was significant only immediately after stimulation.

Conclusions:
High-frequency rTMS of bilateral motor areas using a double cone coil can potentially improve walking function in post-stroke hemiparetic patients.