bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement in Paramedic Examination Skills Following a Stroke Course
Authors: Gordon David Lee , Issenberg S. Barry , LaCombe David M , Vega Alma , Reynolds Patrick S , Harden Ronald M , McGaghie William C , Petrusa Emil R , Hart Ian R
Published: July 2021

P184

Introduction:
The need to decrease time to treatment for acute stroke patients means that prehospital providers must play an increased role in their care. This is possible only if emergency medical services personnel are able to rapidly recognize and assess patients with neurologic syndromes. Purpose: To assess the performance of a focused neurologic exam by prehospital providers before and after participation in an interactive stroke course.
Methods:
We developed a 1-day emergency stroke course that consists of 2 hours of lectures and 6 hours of interactive instruction, including small-group sessions led by paramedic instructors as standardized patients (SPs) portraying 5 key neurologic syndromes: left hemisphere, right hemisphere, brainstem, cerebellum, and subarachnoid hemorrhage. We devised a 53-point skills checklist to evaluate paramedic performance of history, exam, management, and emergency department (ED) reporting during 2 pre- and 2 postcourse encounters with actors portraying one of 4 scenarios: left hemisphere stroke, right hemisphere stroke, right hemisphere seizure with postictal hemiparesis, and left hemisphere tumor with sudden worsening. Among the 53 total skills evaluated were 28 exam-related items, including traditional paramedic exam items such as pupil reaction, hand grasp, and foot strength and additional items from the Miami Emergency Neurologic Deficit (MEND) Exam. We randomly selected 46 of 281 learners to participate in the study.
Results:
Checklist scores for neurologic exam performance improved significantly. The precourse mean score for the 46 learners was 3.38 (12.1%) and the postcourse mean was 21.4 (76.4%) (p<.001).
Conclusions:
Paramedics significantly improved their performance of a focused neurologic exam after attending a stroke course utilizing paramedic instructors as SPs with key stroke syndromes. We conclude that prehospital providers can learn and perform a brief, focused neurologic exam after attending a 1-day stroke course that emphasizes hands-on instruction. We are continuing to evaluate the effect of the course on the history-taking, ED-reporting, and stroke-management skills of practicing paramedics.
Magnesium Sulfate Does Not Increase Ventricular Cerebrospinal Fluid Ionized Magnesium Concentration in Patients with Intracranial Hypertension
Authors: Brewer Randall P , Parra Augusto , Hopkins Michael B , Borel Cecil O , Reynolds James R
Published: July 2021

P197

Background:
Magnesium sulfate (MgSO4) has attracted interest as a neuroprotective agent during cerebral ischemia. Passage of Mg ion into the CNS has been poorly examined. The present study assessed the passage of ionized (physiologically-active)Mg into the cerebrospinal fluid (CSF) of patients with intracranial hypertension after MgSO4 infusion. Design: After IRB approval, patients requiring CSF drainage received IV MgSO
4
(5g)in 125 cc NS over 30 min. Plasma and CSF samples were taken hourly for 4 hrs. Intraventricular catheter placement was confirmed by CT. Data analysis involved ANOVA followed by Dunnet’s post hoc test for a significant F statistic (p < 0.05).
Results:
Nine patients (5/4, male/female; mean age=52) with closed head injury (n=3), subarachnoid hemorrhage (n=2), intracerebral hemorrhage (n=2), hydrocephalus (n=1), and subdural hematoma (n=1) were studied. Mean (±SD)Mg values are presented (table). Baseline Mg was higher in CSF. Although plasma Mg increased, CSF Mg was unchanged.
Conclusions:
Although the CSF to plasma Mg gradient is maintained in patients with intracranial hypertension, intravenous infusion of 5g MgSO4 does not further increase CSF Mg. This suggests systemic infusion of MgSO4 may not be an effective route of administration for neuroprotection.
Warfarin Education and Monitoring in Medicare Patients with Atrial Fibrillation: Results from the National Stroke Project
Authors: Nilasena David S , Kresowik Timothy F , Piskac Anton F , Hemann Rebecca A , Brenton Marian A , Wilwert June M , Hendel Marc E , Nevins Lynnette E
Published: July 2021

P204

Background:
Anticoagulation with warfarin is recommended for stroke prevention for many patients with atrial fibrillation (AF). It is important that patients understand the appropriate use of warfarin and are monitored for optimal drug dosing. As part of HCFA’s initiative, we studied data related to these aspects of warfarin use.
Methods:
Project findings were based on abstracted data from a national sample of Medicare inpatient medical records with a principal or secondary diagnosis of AF (ICD-9-CM code 427.31) and discharged 4/98–3/99. All U.S. states, the District of Columbia and Puerto Rico were sampled using a systematic random approach. Patients included in analysis had documentation of a prescription for warfarin at discharge.
Results:
Of the 38,925 cases reviewed, 14,237 met the inclusion criteria. Nationwide, 2,274 (unadjusted rate, 16.0%) patient/family/caregivers received warfarin education. The rates varied from 5.7% to 26.9%. Univariate analyses showed that education was provided less frequently to adults 85 years and over (p<0.001, rate=11.1%, OR=0.60, 95% CI=0.53–0.69). Education was provided more frequently to Asians (p<0.001, n=77, rate=32.5%, OR=2.55, 95% CI=1.58–4.11) and Native Hawaiian/Pacific Islanders (p<0.03, n=24, rate=33.3%, OR=2.64, 95% CI=1.13–6.17). Of the 14,237 patients that were prescribed warfarin at discharge, 7,959 (unadjusted rate, 55.9%) had a documented plan for a prothrombin time (PT)/International Normalized Ratio (INR). The rates varied from 21.3% to 67.6%. Univariate analyses showed that a planned PT/INR was documented less frequently for adults 85 years and over (p<0.001, rate=52.6%, OR=0.85, 95% CI=0.78–0.93), African-Americans (p<0.005, rate=50.2%, OR=0.79, 95% CI=0.67–0.93) and Asians (p<0.02, rate=41.6%, OR=0.56, 95% CI=0.36–0.88).
Conclusions:
Our results suggest that many patients receiving anticoagulation for stroke prevention are not receiving drug education and follow-up monitoring. Important high-risk subgroups were less likely to receive these aspects of anticoagulation management.
Cellular metabolic alterations after focal cerebral ischemia with or without bone marrow transplantation determined by cytochrome oxidase histochemistry
Authors: Li Yi , Chen Jieli , Chopp Michael , Wang Lei , Zhao Weihang
Published: July 2021

P220

To determine the degree and extent of changes in cellular metabolic demand after stroke and bone marrow cell transplantation, a histochemistry assay of cytochrome oxidase (COx) which correlates with neuronal activity was employed,. Adult Wistar rats (n=9) were subjected to transient (2 h) middle cerebral artery occlusion (MCAo). At 1 d after ischemia, bone marrow stromal cells (MSCs, 4x10
5
in 10 :l) were transplanted intracerebrally into the ischemic boundary zone in the striatum and the cortex. The ischemia rats with (n=4) or without (n=5) MSC transplantation were sacrificed at 14 d after MCAo. Bone marrow cells were harvested from normal donor adult rats and cultured in Iscove s Modified Dulbecco s medium supplemented with 10% fetal bovine serum. MSCs were isolated by their adherence to the plastic dishes from the whole bone marrow cells at 72 h of incubation. Subsequently, the MSCs were cultured for 2 weeks and bromodeoxyuridine (BrdU, as a tracer to identify cells derived from bone marrow) was added into the medium at 3 d before transplantation. Cellular metabolic activity in the ischemic damaged brain was measured on a standard section per animal using quantitative histochemistry of COx with the Global Lab Image Analysis system. Immunohistochemistry staining was employed to identify BrdU-MSCs. COx was absent in the ischemic core in all experimental animals. However, COx activity was intense and prominent in the areas of BrdU-MSCs, as well as the subventricular zone (SVZ) of the adult forebrain. COx (72.8% of the normal hemisphere) was significantly increased (p=0.004) in the ipsilateral hemisphere after MCAo with MSC transplantation, compared with MCAo alone (30.4%). Since MSCs contain a population of marrow stem-like cells and the SVZ of the adult forebrain contains a population of neural stem-like cells, our data indicate that COx provides cellular metabolic evidence that stem-like cells (MSCs and SVZ cells) are activated in response to ischemic brain damage.
Risk of unruptured aneurysm treatment in California
Authors: Johnston S. Claiborne , Zhao Shoujun , Dudley R. Adams , Gress Daryl R
Published: July 2021

P230

Background.
Few studies have directly compared the risk of cerebral aneurysm repair with surgery and with endovascular coil embolization. Since the vast majority of patients with unruptured cerebral aneurysms are non-disabled prior to treatment, this diagnosis provides an opportunity to compare risks of treatment.
Methods.
Discharge abstracts for all patients with a primary diagnosis of unruptured cerebral aneurysm were retrieved from a statewide database of non-Federal hospital discharges in California from January 1990 through December 1998. Admissions for initial treatment and all follow-up care were combined to reflect the entire course of therapy. An adverse event was defined as an in-hospital death or discharge to nursing home or rehabilitation hospital at any point during the treatment course.
Results.
A total of 2069 patients were treated for unruptured aneurysms. Adverse outcomes were more frequent in the 1699 patients treated with surgery than in the 370 treated with endovascular therapy (25% vs. 10%; p<0.0001 by chi-square test). The difference persisted after adjustment for age, gender, race, source of admission, and year of treatment (odds ratio 3.5 for adverse events surgery vs. endovascular therapy, 95% confidence interval 2.4–5.2, p<0.0001 by logistic regression). In-hospital deaths occurred in 3.5% of surgical cases and 0.5% of endovascular cases (p=0.003), and the difference remained significant after adjustment in multivariable models (odds ratio 6.3, 1.5–26.2, p=0.01). Adverse events were less likely at hospitals treating a larger portion of patients with endovascular therapy after adjustment for case characteristics, hospital treatment volume, and clustering of observations using generalized estimating equations (p=0.006).
Conclusions.
In California, endovascular repair of unruptured cerebral aneurysms is associated with fewer adverse events and in-hospital deaths than surgery.
Abstract 10: Rising Trend of Ischemic Stroke in the Young
Authors: Nguyen-Huynh Mai N , Emery Michael H , Sidney Steve
Published: July 2021

Background:
Stroke in patients under 45 years of age occurs less frequently than in older patients but its impact on the individual and society is greater. Recent studies have reported decreasing trends of acute ischemic stroke hospitalization. However, it is less clear what the trends are in different age groups and across different races. We sought to determine trends of ischemic stroke by age, gender and race in a large multi-ethnic population.

Methods:
Northern California Kaiser Permanente (KPNC) is a large multi-ethnic health care system that serves over 3 million members. Membership demographics, socio-economic and racial-ethnic distributions are representative of California. Study patients were identified by primary discharge ICD-9 codes (433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434.01, 434.11, 434.91 and 436) for the period of January 2000 - December 2008. Only one stroke per person per year was included in the analyses. Age-adjusted stroke rates standardized to the 2000 US Census population were calculated. Poisson regression analysis was used to examine trend data.

Results:
From 2000-2008, a total of 25,433 ischemic strokes and 28,438,488 person-years were included in the analyses. Age-adjusted rates of ischemic stroke decreased from 203 to 145 per 100,000 during this time (p<0.001). Rates decreased across all races during study period with the greatest drop among African Americans (from 313 to 261 per 100,000; p<0.001). Decreasing trends were similar between males and females across races. However, ischemic stroke rates among ages 25-44 were on the rise during this time (p<0.001), in particular for Black (from 17 to 39 per 100,000) and for Asian/Pacific Islanders (from 5 to 11 per 100,000) [
Figure
].

Conclusions:
While the overall trend in KPNC showed a decrease in age-adjusted rates for ischemic stroke from 2000-2008, this was mainly true for age ≥ 65 years. There was an alarming rise in the number of ischemic strokes among patients age 25-44 years. Further studies to assess the trends of vascular risk factors such as obesity, hypertension and diabetes are needed to identify future stroke prevention targets in this age group.
Abstract 113: GSK360A Inhibits Prolyl 4-Hydroxylase, Upregulates Hypoxia Inducible Factors (HIF) and Provides Protection from Ischemic Stroke-Induced Injury and Sensory-Motor-Cognitive Deficits
Authors: Zhou Jin , Li Jie , Rosenbaum Daniel , Willette Robert , Lepore John , Hu Erding , Barone Frank
Published: July 2021

Background:
Hypoxia inducible factors (HIFs) are transcription factors that are upregulated by decreased oxygen tension and ischemic preconditioning. HIFs increase angiogenesis, erythropoiesis, cell proliferation/survival and energy metabolism and decrease inflammation. GSK360A is a novel, orally active prolyl 4-hydroxylase (PHD) inhibitor that upregulates HIF-1α signaling and can protect the failing heart. Since GSK360A upregulates systems involved in ischemic tolerance, its administration prior to surgery/ischemia could be beneficial. GSK360A effects in cerebral ischemia have not been explored.

Method:
Male Sprague Dawley rats received 2 hours transient middle cerebral artery occlusion (tMCAO) followed by 22 hours of reperfusion. GSK dose selection was based on previous pharmacodynamic data on HIF system upregulation that was verified in these studies. Vehicle (1% Methyl cellulose) or GSK360A (30 mg/kg) was administered by oral gavage at 18 and 5 hr prior to tMCAO. Measurements were made of kidney erythropoietin (EPO) mRNA and protein over 1 day, modified neurological severity score (mNSS) over 5 and 24 hrs, cognitive performance (Active Place Avoidance; APA) and motor activity at 3-4 weeks and terminal brain infarction were made. Different groups of rats (N=5-10 per group) were studied over 1 day to 4 weeks.

Results:
GSK360A increased kidney EPO mRNA and protein up to 80-fold (p<0.01) by 5 hr post-stroke. Stroke increased mNNS that was reduced by GSK360A (31% and 20%, p<0.05) at 5 and 24 hr post-stroke onset. Stroke-induced decreases in APA performance, reflecting cognitive dysfunction, was reduced (p<0.01) by GSK360A without affecting motor activity. GSK360A also reduced brain infarction (30%, p<0.05).

Conclusions:
This is the first demonstration of GSK360A brain protection and long-term improvement in post-stroke neurological outcome, including beneficial effects to reduce stroke-induced loss in cognitive function. These data suggest that pre-stroke administration of GSK360A can produce PHD inhibition that stimulates HIF signaling useful for high-stroke-risk situations. In addition, its use prior to surgery might reduce the probability of post-surgical cognitive decline.
Abstract 126: Wingspan Stent Largest Series Outside SAMMPRIS: Long-term Results
Authors: Chitale Rohan , Toporowski Amy , Cheresnick Corey , Tjoumakaris Stavropoula , Gonzalez Fernando , Dumont Aaron S , Rosenwasser Robert H , Jabbour Pascal
Published: July 2021

Objective:
Intracranial stenosis is a common culprit for stroke which has been traditionally managed with medical therapy. However, recurrent TIA or stroke symptoms often occur despite aggressive management with antiplatelet medications. As such, angioplasty and stenting of intracranial vasculature has become an attractive idea for treatment of intracranial stenosis refractory to medical treatment. Because the SAMMPRIS trial was terminated prematurely, long term data regarding efficacy is lacking. We present the results of our series of 61 patients who underwent Wingspan stent placement for intracranial stenosis and evaluate the short-term and long-term success.

Methods:
Sixty-one patients with high-grade, symptomatic intracranial stenosis underwent Wingspan stent embolization at Jefferson Hospital for Neuroscience from August 7, 2006 to July 13, 2011. The clinical charts were reviewed to evaluate presentation, intervention, perioperative course, and outcome.

Results:
Our series consisted of 61 patients who received a Wingspan stent for intracranial stenosis(41 male; 20 female; mean age 62.9). Stenotic vessels treated included the internal carotid artery(n=18), middle cerebral artery(n=13), basilar artery(n=15), vertebrobasilar junction(n=2), and vertebral artery(n=13). Failure of stent placement was the only identified intraoperative complications, occurring in 6.6% of procedures. Perioperative complications occurred in 6.6% of patients, and included myocardial infarction(n=1), TIA or stroke without in-stent thrombosis(n=1), TIA or stroke with in-stent thrombosis(n=2), and death(n=2). Mortality rate was 3.3% in the perioperative period. Follow-up data was available for 41(67.2%) patients, with a mean duration of 205 days after intervention. In this follow-up group, 9.8%(n=4) suffered delayed in-stent thrombosis, 3(7.3%) of which suffered new TIAs or stroke. There was 1(2.4%) delayed mortality related to pseudoaneurysm rupture at the site of the stent.

Conclusion:
We present the largest series of patients outside of SAMMPRIS to undergo Wingspan stenting for intracranial stenosis. Immediate and long-term follow-up data demonstrates the safety profile of the procedure with efficacy in preventing future strokes. Delayed in-stent thrombosis is the most common risk to observe in this patient population.
Abstract 142: Use of Stroke Prevention Medications in Self-Reported Stroke/TIA: The REGARDS Study
Authors: Anderson Aaron M , McClure Leslie A , Kingston Carlene W , Safford Monika M , Frankel Michael R , Howard Virginia J , Kleindorfer Dawn O
Published: July 2021

Introduction:
Guidelines recommend specific classes of medications for secondary stroke prevention. In this analysis we are interested in whether the use of antiplatelet, anticoagulant, anti-hypertensive, and lipid lowering medications differs by race and region among participants who self-reported stroke or TIA in a national, general population sample.

Methods:
Data were derived from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a national cohort study of 30,239 black and white participants aged 45+ enrolled between 2003 and 2007 from the 48 contiguous states, with over-sampling in the southeast region known as the stroke belt and buckle.A centralized phone interview was used for medical history and in-home evaluation for medication inventory. All medications used in the previous two weeks were recorded and subsequently coded into drug classes. The dataset was restricted to those with self-reported stroke (1930) or TIA (1114) at baseline. Chi-square tests were used to determine racial and regional (non-belt, belt, buckle) differences in the use of each medication classification, though indication or contraindication for treatment is unknown. Separate univariate logistic regression models were fit to assess the association between each medication class and race and region. Incremental models (demographics, SES factors, health behaviors, and co-morbidities) were then fitted to determine the impact of adding groups of covariates on the associations. Odds ratios and 95% confidence intervals (CI) for the association between each of race and region, and each medication class, were computed.

Results:
The results from the univariate and fully-adjusted models are presented in
Table
1. After multivariable adjustment, blacks were less likely than whites to report using antiplatelet and lipid-lowering medications, while the belt and buckle residents were more likely than non-belt residents to report antiplatelets.
Table 1:
Association between Medications and Race and Region, univariate and adjustment. (95% CI) Adjusted model includes demographics, SES, health behavior, and co-morbidities. Whites and non-belt region serve as reference for logistic regression models of race and region, respectively.

Conclusions:
These data indicate differential use of antiplatelet therapy by race and region, and lipid lowering therapy by race, in those self-reporting stroke/TIA, with differences in use of anticoagulant and antihypertensive medications accounted for by covariant adjustment. This suggests targeted interventions are needed following stroke/TIA.
Abstract 159: Current Treatment with Clotting Factors Does not Improve Outcome from Intracranial Hemorrhage After Thrombolysis for Acute Ischemic Stroke
Authors: Alderazi Yazan J , Barot Niravkumar V , Misra Vivek , Grotta James C , Savitz Sean I
Published: July 2021

Objective & Background:
Significant intracranial hemorrhage (sigICH), defined as either symptomatic intracerebral hemorrhage SICH or parenchymal hematoma type 2 (PH2), is a concerning complication of thrombolysis for acute ischemic stroke (AIS). While clotting factors have been incorporated into clinical protocols, the effectiveness of such treatment for sigICH has not been evaluated. We investigated the effects of clotting factors, fresh frozen plasma FFP and cryoprecipitate, in patients with sigICH post thrombolysis.

Methods:
We retrospectively evaluated all patients with sigICH after TPA for AIS in the prospective University of Texas at Houston Stroke registry; January 2007 - July 2011. We included all patients who received TPA for AIS and subsequently developed sigICH. Patients either received clotting factors (FFP or cryoprecipitate) or conservative management. The primary outcome measure was modified Rankin scale at discharge. The other outcome was death. We collected data on confounding variables: Stroke risk factors, infarct prognostic variables and intracerebral hematoma prognostic variables. Statistical analysis was by Fisher-exact, Chi-square and Mann-Whitney-U tests.

Results:
Out of 921 patients receiving TPA, sigICH occurred in 50. We excluded 3 because of enrollment in clinical trials. Out of 47 patients, 37 received IV TPA alone and 10 received IV TPA with subsequent intra-arterial therapy. Clotting factors were given in 22/47 (46.8%) patients; 18 received FFP & 9 received cryoprecipitate. The rest received no specific therapies for hemorrhage. There was no difference in stroke severity between groups before and after TPA. The incidence of hydrocephalus was higher in patients receiving clotting factors. There were no differences in outcomes at discharge in either group; the majority of patients in both groups had poor outcomes (mRS was >3). Mortality was high and not different between the two groups. Fibrinogen levels before and after clotting factors did not significantly differ from the patients who received only conservative management. Table 1.

Conclusions:
We found that clinical outcome of sigICH post TPA is poor. Furthermore, our data suggest that clotting factors do not improve the poor outcome associated with sigICH after t-PA. Our study is limited by small sample size, and the higher incidence of hydrocephalus in those receiving clotting factors may have influenced the outcomes. Nevertheless, our data suggest that new therapies are urgently needed for t-PA associated intracranial hemorrhage.
Abstract 176: Largest United States Pipeline Case Series After PUFS: Feasability, Technique, and Complications
Authors: Chitale Rohan , Gonzalez Fernando , Randazzo Ciro , Dumont Aaron S , Tjoumakaris Stavropoula , Rosenwasser Robert H , Dayoub Hayan , Jabbour Pascal
Published: July 2021

Largest US Pipeline Case Series After PUFS: Feasability, Technique, and Complications

Object:
Endovascular coil embolization is an established method of treatment for intracranial aneurysms. Incomplete occlusion and recanalization are potential pitfalls of this treatment, particularly in large, complex aneurysms. The pipeline embolization device(PED) is a low-porosity endovascular stent designed to reconstruct the parent artery and prohibit blood flow into the aneurysm. The resulting stasis in the aneurysm, which leads to thrombosis, and the subsequent endothelial incorporation of the stent is meant to provide curative protection from aneurysmal rupture. Following the FDA approval of the PED, the authors report the first case series of 25 patients who have undergone such embolization and examine feasibility, technique, early results, and complications.

Methods:
Twenty-five patients underwent PED placement for aneurysm at Jefferson Hospital for Neuroscience from October 2010 to July 2011. Clinical charts were reviewed for demographics, details of presentation, procedure, hospital course, and outcome.

Results:
Twenty-five patients with 31 aneurysms were treated in the series(2 male; 23 female; ages 34-82; mean age 60.9 years). All of the aneurysms were located in segments of the internal carotid artery(1 petrous, 1 lacerum, 13 cavernous, 2 clinoid, 12 ophthalmic, 2 superior hypophyseal). Patients presented with headache, cranial nerve palsy, TIA, recurrence, or as incidental findings. Four of the patients presented with recurrence after coil embolization; one patient was treated with PED after attempted coil embolization; one was treated for recurrence after prior PED placement. PED placement was successful in all patients. The number of stents used per patient ranged from 1 to 5, with most patients being treated with 1(n=6) or 2(n=13) PEDs. One aneurysm was treated with both PED and coil embolization. A postoperative complication or combination of complications were witnessed in 20%(n=5) of patients. These complications included intracerebral hemorrhage(n=3), dissection(n=1), stroke(n=2), and death(n=1). Follow-up angiograms have been performed for five patients, on average 31 days after embolization, with 1 of those 5 patients suffering from incomplete aneurysmal occlusion.

Conclusion:
This is the largest reported case series in the United States following the PUFS trial. Treatment of simple or complex intracranial aneurysms with PEDs alone or in conjunction with coil embolization is technically feasible with low chance of intraoperative complication. However, major perioperative adverse events must be studied. Respect for the indications of the procedure is crucial to justify the risk.
Abstract 182: Death and Disability after Coil Embolization of Ruptured and Unruptured Aneurysms in the Matrix And Platinum Science (MAPS) Trial
Authors: Johnston S Claiborne , McDougall Cameron , Gholkar Anil , Turk Aquilla ,   The MAPS Investigators
Published: July 2021

Introduction:
We sought to evaluate overall rates of disability and mortality in patients treated with coil embolization for unruptured and ruptured intracranial aneurysms who were enrolled in the MAPS trial, a multicenter randomized trial that showed that Matrix
2
biocompatible absorbable polymer-coated coils were noninferior to GDC bare-platinum coils.

Methods:
We conducted a randomized trial with blinded outcome assessment performed at 43 centers worldwide. Eligible patients were 18-80 years old with a single documented untreated intracranial saccular aneurysm, 4-20 mm, unruptured or non-disabled ruptured (Hunt and Hess score I-III, modified Rankin Scale [mRS] score 0-3) for which both Matrix
2
and GDC coils were treatment options, and for which primary coiling treatment was planned to be completed during a single procedure. mRS was assessed at baseline and 1 year follow-up, and predictors of disability or mortality (mRS>3) and a worsening in the mRS were evaluated in univariate and multivariable models using logistic regression. The trial was registered at Clinicaltrials.gov as
NCT00396981
.

Results:
Among 626 subjects enrolled, 568 had an mRS assessment available at 1 year, of whom 208 initially presented with a ruptured aneurysm and 360 with an unruptured aneurysm. During 1 year follow-up, 24 had died (3.8%), of which 7 (1.2%) were judged device or procedure related by the clinical events committee; another 11 were disabled (1.8%). Rates of death or disability were greater for ruptured aneurysms (9.6%) than for unruptured aneurysms (4.2%, p=0.011); however, rates of worsening in mRS were similar (ruptured 11.7% vs. 10.3%, p=0.599). Rates of death and disability were similar for those randomized to GDC compared to Matrix (p=0.616), as were rates of worsening of mRS (p=0.471). Independent predictors of death or disability were older age (per decade, OR 2.1, 95% CI 1.4-2.9, p<0.001), ruptured at presentation (OR 2.4, 1.1-5.2, p=0.029), and current use of illicit drugs or alcohol (OR 4.3, 1.4-13, p=0.011). Coil type (GDC vs. Matrix), other clinical characteristics, aneurysm characteristics, and retreatment were not predictors of death or disability in univariate or multivariate models.

Conclusions:
Coil embolization of intracranial aneurysms is rarely associated with death or disability, with overall rates generally lower than previously reported. Although older age and initial rupture are known to be associated with worse outcomes, use of illicit drugs or alcohol was also a predictor but requires independent validation.
Abstract 206: Pre-notification by Emergency Medical Services is Associated with More Timely Evaluation and Treatment of Acute Ischemic Stroke
Authors: Lin Cheryl , Peterson Eric D , Smith Eric E , Saver Jeffrey L , Liang Li , Shah Bimal R , Xian Ying , Olson DaiWai M , Hernandez Adrian F , Schwamm Lee H , Fonarow Gregg C
Published: July 2021

Background:
The benefits of intravenous tissue-plasminogen activator (tPA) in acute ischemic stroke are time-dependent. Emergency medical services (EMS) pre-notification of stroke arrivals may provide a means of reducing evaluation and treatment times. In this study we used data from the nationwide Get With The Guidelines Stroke (GWTG-Stroke) program to determine the effect of EMS pre-notification on acute ischemic stroke processes of care.

Methods:
Acute ischemic stroke patients transported by EMS to 1585 GWTG-Stroke hospitals from April 2003 to March 2011 were studied. The association between EMS pre-notification and door-to-imaging (DTI) times, door-to-needle (DTN) times, onset-to-needle times (OTN), and tPA treatment rates were analyzed using multivariable GEE regression analyses.

Results:
Of 371,988 EMS transported acute ischemic stroke patients, EMS pre-notification occurred in 249,197 (67.0%). Patients with pre-notification had shorter door-to-imaging times, shorter onset-to-needle times, and were more likely to be treated with tPA when eligible (
Table
). EMS pre-notification was independently associated with increased odds of DTI ≤25 minutes (adjusted OR 1.53, 95% CI 1.44–1.63, p<0.0001), DTN times ≤60 minutes (aOR 1.20, 95% CI 1.10–1.31, p<0.0001), OTN times (aOR 1.17, 95% CI 1.09–1.25, p<0.0001), and tPA use within 3 hours among eligible patients arriving by 2 hours (aOR 1.64, 95% CI 1.50–1.79, p<0.0001), without significant increases in complications of thrombolytic therapy.

Conclusion:
EMS pre-notification is independently associated with more rapid patient imaging and increased timeliness in IV tPA administration. These results support the need for initiatives targeted at increasing EMS pre-notification rates as a mechanism from improving quality of care and outcomes in acute ischemic stroke.
Abstract 2188: Bleeding Events and Anticoagulant Discontinuation in Patients with Atrial Fibrillation
Authors: Suh Dong-Churl , Nelson Winnie , Choi Jiyoon , McGuire Michael
Published: July 2021

BACKGROUND:
Annually, about 2.3% of patients receiving warfarin prophylaxis experience major bleeding. Discontinuation of warfarin due to hemorrhage can leave patients unprotected against potential stroke.

OBJECTIVE:
To assess the rate of warfarin discontinuation and identify factors associated with warfarin discontinuation among patients with atrial fibrillation (AF).

METHODS:
Retrospective cohort study was conducted using the Market Scan Database between1/12005 and 6/30/2008. Study patients were ≥18 years old with ≥2 AF diagnoses where at least one diagnosis was prior to the first warfarin prescription (index). An additional warfarin prescription within 6-months after index date was required to ensure continuous treatment. Patients were excluded if they had previous warfarin treatment or a cardioversion during one year history period. Continuous health benefit coverage was required during study period. Patients were followed until a hemorrhagic event, warfarin discontinuation, or end of study period. Discontinuation was defined by ≥90 days without a refill after depletion of the drug supply from the prior prescription claim. Recent hemorrhage was defined as hemorrhage within 90 days before discontinuation. Multiple regression analyses were conducted to identify the factors associated with warfarin discontinuation.

RESULTS:
7,971 patients met study eligibility criteria. Mean (±SD) patient age was 67.8 (±12.7), with majority ≥65 years old (59.3%). 41.2% were female. During follow-up, 51.7% of patients discontinued warfarin (p<.001). A higher proportion of patients who had a recent hemorrhage (61.8%) discontinued warfarin compared to those without (51.3%). After adjustment, patients with a recent hemorrhage were 35% more likely to discontinue warfarin, compared to those without (RR=1.35; CI:1.16-1.58). Age of ≥85 (reference: <65), and history of ≥1 hospitalization or emergency room visit were associated with increased likelihood of discontinuation (all p<.001). Female, daily doses>5mg (reference: ≤5mg), concomitant use of gastroprotective agents, and CHADS2 scores ≥1 were associated with decreased likelihood of discontinuation (all p<.05).

CONCLUSIONS:
In this retrospective cohort, half of AF patients receiving warfarin discontinued their treatment. A recent hemorrhage was associated with an increase in discontinuation. A novel therapy with a predictable profile may help minimize bleeding risk and treatment discontinuation.
Abstract 2219: Trevo System: Single Center Experience With A Novel Mechanical Thrombectomy Device
Authors: Mendonça Nuno M , Flores Alan , Pagola Jorge , Rubiera Marta , Rodríguez-Luna David , Mora Paloma , De Miquel M Angels , Cardona Pere , Quesada Helena , Alvarez-Sabín José , Molina Carlos , Ribó Marc
Published: July 2021

Background and Purpose:
Recent reports have indicated that mechanical thrombectomy may have potential as a treatment for acute ischemic stroke. This study aims to describe the safety and effectiveness of Trevo RetrieverTM (Concentric Medical Inc, Mountain View, California) using StentrieverTM technology, in revascularization of patients with acute ischemic stroke.

Methods:
Prospective study evaluating the clinical, radiological and functional outcome of 13 patients with an angiographically verified occlusion of the anterior cerebral circulation. All patients underwent thrombectomy with TR as monotherapy or in combination with intra-arterial thrombolysis, within the first 8 hours from symptoms onset. Successful revascularization was defined as thrombolysis in cerebral ischemia grade 2a to 3. Good outcome was defined as modified Rankin Scale score ≤ 2.

Results:
Median baseline NIHSS score was 19 (16-22). The occlusion site was MCA in 8 patients and ICA in 5 patients. Five patients received IV tPA before endovascular procedure. Revascularization was achieved in 10 of 13 patients (77%). The median number of passes for maximal recanalization was 2 (1-3) and the mean time from groin puncture to recanalization was 95±31 minutes. No significant intra-procedural complications occurred. Four patients (30%) died during the 90-day follow-up period and 4 patients (30%) achieved functional independence at 3 months.

Conclusions:
Early clinical experience suggests that the TR can allow safe and effective revascularization in certain subjects with acute ischemic stroke.
Abstract 2305: Endothelin-1 Alters Nitric Oxide-Dependent Cerebrovascular Responses by Modulating The Phosphorylation State of eNOS via Rho Kinase
Authors: Faraco Giuseppe , Anrather Joseph , Iadecola Costantino
Published: July 2021

Hypertension (HTN) alters vital homeostatic mechanisms regulating cerebral blood flow (CBF) and increases the risk of stroke and dementia. HTN exerts some of its damaging effects by counteracting the beneficial vascular actions of nitric oxide (NO). The potent vasoconstrictor endothelin-1 (ET1) has been implicated in the pathogenesis of HTN, but its role in the cerebrovascular effects of HTN is unknown. We examined whether ET1 disrupts CBF regulation. CBF (laser-Doppler flowmetry) was assessed in the somatosensory cortex in anesthetized male C57Bl/6 mice (n=5/group) equipped with a cranial window. ET1 (35 pmol/kg/min; i.v. for 45 min) increased mean arterial pressure from 72±4 to 99±6 mmHg (p<0.05), without reducing resting CBF (p>0.05). However, ET1 attenuated the CBF increase produced by neocortical application of the endothelium-dependent vasodilator acetylcholine (ACh; -37±1%; p<0.05) and by whisker stimulation (-31±1%; p<0.05), responses dependent on NO. The CBF response to adenosine was intact (p>0.05) indicating that ET1 did not act by compromising smooth muscle relaxation. The effects of ET1 were prevented by the ET type A (ET
A
) receptor antagonist BQ123 (1µM; p<0.05), by the Rho kinase (ROCK) inhibitor Y27632 (1 µM; p<0.05), but not by the ET
B
antagonist BQ788 (100nM; p>0.05). ET-1 did not affect the CBF increase produced by the NO donor SNAP and did not increase free radicals, suggesting that ET-1 did not act by reducing NO vasoactivity or bioavailability. However, in brain endothelial cell cultures ET1 (10-100nM) attenuated the NO production induced by ACh (-49±4% at 50nM; p<0.05), an effect blocked by BQ123 and Y27632. ET1 increased eNOS phosphorylation at Thr495, which inhibits eNOS, and reduced phosphorylation at Ser1177, which activates eNOS, effects blocked by Y27632. These findings, collectively, suggest that ET1 alters key regulatory mechanisms of the cerebral circulation by modulating the phosphorylation state of eNOS via ROCK. The resulting downregulation of eNOS activity is responsible for the neurovascular dysregulation induced by ET1. ET
A
receptors may be a valuable target to counteract the deleterious cerebrovascular actions of HTN.
Abstract 2379: A Comprehensive Imaging Informatics System with Decision-Support Tools for the Interdisciplinary Comprehensive Arm Rehabilitation Trial
Authors: Winstein Carolee J , Liu Brent , Dromerick Alexander , Butler Andrew , Wolf Steven , Wang Ximing
Published: July 2021

BACKGROUND:
Stroke is one of the major causes of death and disability in America. The Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) project aims to compare a theoetically-defensible, evidence-based arm therapy, Accelerated Skill Acquisition Program, with traditional therapies. Imaging of the brain provides evidence of the location and severity of the stroke lesion. Researchers can analyze selected images acquired prior to enrollment and perform knowledge discovery of correlation between the size and location of the lesion and specific rehabilitation outcomes. However, large-scale trials such as ICARE encounter challenges for integrating imaging data from multiple healthcare institutions across the country. The ICARE project has 7 clinical sites distributed across the country, with more than 160 patients randomized thus far, tens of gigabytes of imaging data are involved. Therefore, we propose to develop a web-based system with tools that can support imaging and informatics related data within such a randomized controlled trial and allow for tele-consultation and collaboration.

EVALUATION:
The system includes a database and file storage system, a Health Insurance Portability and Accountability Act (HIPAA)-compliant anonymizer, a web-based Graphical User Interface (GUI) and decision-support tools such as lesion quantifying tools and image analysis. The GUI allows users to upload, search and review the images, patient information and annotations. The HIPAA-compliant anonymizer will anonymize any private information according to HIPAA. The lesion quantifying tool will help clinicians to measure, quantify, and characterize the size of lesion and evaluate the rehabilitation progress. The system will be used within 7 clinical sites and evaluated by researchers in the ICARE trial.

DISCUSSION:
The system allows for tele-consultation and is facilitated through the development of a thin-client image viewing application. Clinicians and researchers across the country can manage the imaging data, make and store annotations, measure the lesion size, and collaborate to identify the imaging biomarkers that would ultimately enhance the existing ICARE clinical trial database. Moreover, the anonymizer tool can be used not only for imaging data in this rehabilitation trial, but also for other data from multi-site clinical trials since most studies are required to be anonymized.

CONCLUSION:
A comprehensive imaging informatics system for a large-scale controlled stroke rehabilitation trial is developed. Physicians and clinical researchers are able to collect, organize and analyze stroke cases efficiently and effectively across multiple sites.
Abstract 2433: Outcomes Of Thrombolysis In The 0-4.5 Hour Time Window In Acute Stroke Patients Selected Using Ct Perfusion Imaging
Authors: Sztriha Laszlo , Manawadu Dulka , Bodla Shankaranand , Jarosz Jozef , Kalra Lalit
Published: July 2021

Background:
Thrombolytic treatment within 4.5 hours of symptom onset is effective in preventing death or significant disability in 1 out of 7 stroke patients, but with a 5% risk of symptomatic intracerebral haemorrhage (sICH). We hypothesised that patient selection using CT perfusion (CTP) imaging can increase the benefit of thrombolysis and reduce the risk of sICH.

Methods:
We extracted data from a prospective thrombolysis database of 533 consecutive stroke patients of all ages thrombolysed with 4.5 hours of symptom onset. Thrombolysis decisions were made on the basis of a non-enhanced CT (NECT) scan but CTP was undertaken in a proportion of patients, depending upon physician decisions. In the analysis, patients with an Alberta Stroke Program Early CT Score (ASPECTS) of ≥7 on NECT and an estimated volumetric perfusion mismatch of ≥100% on PCT were defined as optimal candidates for thrombolysis. Imaging was reviewed by 2 raters masked to outcomes. Nine patients were excluded from analysis because of poor PCT quality.

Findings:
Of the 524 patients included, 97 patients had CTP mismatch that met the defined criteria for mismatch guided thrombolysis. Their age (72 v 70 years), sex (50% v 54% male), pre-morbid modified Rankin Scale (mRS) score, baseline National Institute of Health Stroke Scale (NIHSS) score (13.6 v 12.6,p=0.20), blood glucose (6.8 v 6.6 mmols) and blood pressure (149/84 v 148/79 mm Hg) were comparable with those thrombolysed on the basis of NECT imaging. At 3 months, the proportion of patients with modified Rankin Score of 0-1 and 0-2 was higher in those with mismatch (36% v 29%, p=0.003 and 51% v 42%, p=0.007 respectively) and there was a non-statistical trend towards reductions in any ICH (13% v 16%), sICH (1.1% v 2.8%) and mortality (23% v 18%). CTP mismatch was an independent determinant of a favourable outcome at 3 months in regression analyses to adjust for covariates.

Conclusions:
Patient selection based on estimation of salvageable brain tissue using CTP mismatch may improve functional outcomes at 3 months. The value of CT perfusion in increasing the effectiveness and safety of thrombolysis within established therapeutic time windows merits investigation.
Abstract 2487: Ischemia/Reperfusion Injury Impairs Myogenic Tone of Cerebral Vessels in both Ischemic and Nonischemic Hemispheres: Differential Role of Oxidative Stress.
Authors: Coucha Maha , Li Weiguo , Ergul Adviye
Published: July 2021

Cerebrovascular autoregulation and reactivity are critical to maintain constant perfusion during ischemic brain injury. It is known that ischemia/ reperfusion (I/R) injury and resulting oxidative stress impair vessel reactivity in ischemic hemisphere. Yet the behavior of vessels in nonischemic hemisphere is still unexplored.

Hypothesis:
I/R injury impairs myogenic tone of vessels in both ischemic and nonischemic hemispheres via increased peroxynitrite (ONOO
-
) generation.

Methods:
Middle cerebral arteries (MCA) isolated from age matched male Wistar rats (n=6) subjected to 30 min MCA occlusion (MCAO)/45 min reperfusion, or MCAO followed by treatment with ONOO
-
scavenger FeTPPs (20mg/kg) at reperfusion were pressurized in arteriograph chamber. In another set of animals, MCA isolated from control Wistar rats were exposed to
ex vivo
oxygen-glucose deprivation (OGD) then their myogenic tones across the pressure range were determined.

Results:
I/R injury impaired myogenic tone of vessels in both ischemic and nonischemic sides albeit to a different degree. Interestingly FeTPPs restored myogenic tone of vessels from ischemic side only (
Table
). Vessels exposed to ex vivo and in vivo hypoxia experienced loss of myogenic tone. The reduction of myogenic tone % by OGD is similar to I/R injury.

Conclusion:
Our ex vivo model of hypoxia is a valuable method to assess the ischemic insult on vessel reactivity. Increased ONOO
-
production is one of the underlying mechanisms of loss of tone under I/R injury in ischemic hemisphere, but the impairment of myogenic tone in nonischemic hemisphere involves other mechanisms. Understanding how I/R alters myogenic tone and ultimately cerebral perfusion in both ischemic and nonischemic hemispheres is vital in improving current preventive and therapeutic strategies for acute stroke.
+
p<0.001,
*
p< 0.05 vs Sham, # p<0.001 vs ischemic MCA ,
**
p<0.01 vs nonischemic MCA