bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3387: Community Education: A Statewide Effort
Authors: Rindels Erin , Overton Angie , Hamm Terri , Handler Diane , Fowler Susan , Thoe Jennifer
Published: July 2021

Background:
The fourth leading cause of death for all Iowans is stroke. Southeast Iowa has higher mortality rates from stroke than northeast Iowa which indicates a geographic disparity in stroke care in Iowa. The stroke death rate in Iowa has decreased by 30% since 2000; however several risk factors for stroke among Iowans have increased since 2000. Iowa has 12 Primary Stroke Centers (PSC) that are located through out Iowa. The stroke coordinator at each PSC is a member of the Iowa Stroke Coordinator Consortium (ISCC). A goal of the ISCC is increasing stroke education to all Iowans.

Purpose:
To provide stroke education across Iowa, including recognition and appropriate response to stroke signs and symptoms.

Method:
The stroke coordinators of the 12 PSCs were asked to conduct a mock stroke drill. Two additional coordinators who are active in the Iowa Stroke Task Force, whose hospitals are not a PSC, were also asked to participate. Coordinators were asked to develop a scenario and conduct a mock stroke event in a public or in a hospital setting and summarize the event.

Results:
Ten hospitals participated in the event. Door to needle times were reported by five hospitals. These reported door to needle times were all less than 60 minutes. Six mock stroke events were conducted in public locations. The public locations included a farmer’s market, office building, sports arena, senior center, and two supermarkets. The remaining mock stroke events were conducted within a hospital. Public events included a debriefing of the event, review of stroke symptoms and response to stroke symptoms. One public event was featured in the local newspaper, and another on the local TV news. The mock stroke drills conducted within hospitals were beneficial in identifying opportunities for improvement in the response to stroke signs and symptoms. The staff involved was debriefed on the event and internal processes for stroke response were reviewed.

Conclusion:
The ISCC achieved its goal by conducting ten different mock stroke drills across Iowa. Each drill focused on the recognition of stroke signs and symptoms, and the appropriate response to stroke symptoms. The state wide mock events were conducted in collaboration with local communities, emergency services personnel, emergency room staff, and ancillary hospital staff. Future goals of the ISCC are developing more defined criteria for a mock event, an evaluation process after the event, and provide education on stroke risk factors to Iowans.
Abstract 3393: The Effect Of Carotid Revascularization On Patients With Baseline Cognitive Impairment
Authors: Breen Thomas , Curran Jill , Stabile Lauren , Ghogawala Zoher
Published: July 2021

Objectives:
The effect of carotid revascularization on cognitive function is controversial. The goal of this study was to assess the degree of cognitive improvement following carotid revascularization in patients with baseline cognitive impairment.

Methods:
Patients with carotid stenosis >60% were enrolled prospectively from 3 sites from 2005 to 2010. Patients underwent either carotid endarterectomy or carotid artery stenting. Neuropsychological testing was administered pre-operatively, 1 month, 6 months, and 1 year post-operatively. Cognitive assessments included Trails A (attention), Trails B (executive functioning), and Hopkins Verbal Learning Test (HVLT-R) (new learning/memory). A baseline cognitive impairment was defined as a score ≤ 10
th
percentile of age-adjusted normative data.

Results:
Of 61 eligible patients, 49 (80%) completed testing at 6-months and/or 1-year post-operatively. Mean age was 73.1 years, 56% were male, and 30% were symptomatic. Pre-operative Trails A impairment was observed in 16% of patients, Trails B in 27%, and a component of HVLT-R in 41%. Following revascularization, patients with a baseline cognitive impairment demonstrated an average improvement of 28.6% and 22.8% in Trails A and B, compared to 4.3% (p=0.04) and 9.2% (p=0.06) in patients with normal baseline cognitive function (
Figure 1
). Similarly, impaired patients exhibited average improvements of 36.5% in HVLT-Total Recall, 38.5% in Delayed Recall, and 36.7% in Retention, compared to 11.0% (p=0.004), 6.1% (p=0.004), and 0.97% (p=0.002), respectively, in patients with normal cognitive function (
Figure 1
).

Conclusion:
Baseline cognitive impairment in attention, executive functioning, and new learning/memory appear to be significant variables in predicting which patients experience the greatest cognitive benefits following carotid revascularization.
Abstract 3431: A High Vascular Risk Factors Profile Predicts Lacunar Stroke Progression
Authors: Nannoni Stefania , Palumbo Vanessa , Del Bene Alessandra , Pracucci Giovanni , Inzitari Domenico
Published: July 2021

Background.
Lacunar stroke (LS) accounts for a quarter of all ischemic strokes and is considered to have a benign prognosis. However, 20-30% of patients experience worsening of neurological deficit in hours or days after stroke onset. Mechanisms of progression are not known and no reliable clinical predictor has been identified. Aim of this study was to explore vascular risk factors and baseline clinical or laboratory features potentially associated with progression in LS.

Methods.
We performed a retrospective analysis of consecutive patients with LS admitted to the Stroke Unit of Careggi University Hospital (Florence, Italy) between January 2002 and December 2010. Patients were included in the study if they presented with a lacunar syndrome according to OCSP classification and/or small vessel disease according to TOAST classification and/or a lacunar infarct on neuroimaging consistent with the clinical deficit. Patients were divided into “progressive” and “non progressive”. Progression was defined as an increase of at least one point on one of the motor items of the NIHSS during the first 72 hours after stroke onset. Factors associated with progression after univariate analysis were entered into a multiple logistic regression model in order to select independent determinants of progression.

Results.
Out of 1502 patients with ischemic stroke admitted during the study period, 156 met the inclusion criteria. Thirty-nine (25%) patients showed neurological worsening. Latency of progression was 25.7 hours. Patients who progressed were younger than those who did not (mean age: 67.9±10.7 vs 70.6±13.0). There were no significant differences for single vascular risk factors distribution, laboratory parameters and baseline stroke severity comparing the two groups. When considering the presence of one versus more than one factor among hypertension, diabetes, smoking and hypercholesterolemia, the risk of progression increased with increasing number of risk factors: neurological worsening was observed in 0% (0/17) of patients with no risk factor, 24% (15/62) of those with one risk factor and 31% (24/77) of those with more than one risk factor (p=0.025). After adjustment for univariate predictors (age, sex, diastolic hypertension and lesion location in pons or internal capsule), the presence of multiple vascular risk factors maintained an independent effect on progression: risk of progression increased with an OR=1.7 (95%IC=1.1-2.8) for any additional risk factor.

Conclusion.
Our results suggest that a high risk factors profile is associated with an increased risk of progression. Translating this observation into a hypothetical pathological setting, it could support the hypothesis of mural atheroma involving the parent artery and proximal portion of the perforating arteries, eventually leading to the progressive enlargement of the ischemic area as a putative mechanism of progressive LS.
Abstract 3463: Physicians’ Knowledge of Driving Limitation Following Stroke or TIA is Inadequate
Authors: Pryce-Roberts Adele , Batool Saiqa , Manawadu Dulka
Published: July 2021

Background:
An increasing number of TIA and minor stroke patients are assessed and discharged by front-line staff in emergency or acute assessment units. As capacity to drive is affected by a stroke or TIA, we assessed the level of knowledge of driving restrictions after stroke or TIA in frontline doctors.

Method:
A structured multiple choice questionnaire was used to assess knowledge of driving restrictions after stroke in 195 doctors involved in assessing patients in the Emergency Department or acute assessment units. The questionnaire took between 10-15 minutes to complete and tested knowledge of driving restrictions after minor stroke or TIA for those holding a domestic (Group 1) or a commercial (Group 2) licence. The wording of the questions was similar to that used in statutory medical guidance by the Licensing Authority.

Results:
The 195 doctors included 8 consultants, 88 senior residents, 22 junior residents and 77 foundation level trainees. Only 43 (23%) doctors had been specifically instructed about driving restrictions in stroke; 89 (45%) had received no formal education on driving restrictions following medical illnesses. The majority (155, 86%) were aware that it was patients’ responsibility to inform the licensing agency of driving restrictions due to medical illnesses. Only 72 (37%) and 84 (43%) doctors correctly identified that TIA patients were not allowed to drive for 1 month if holding a domestic licence and for 1 year if holding a commercial licence respectively. Forty eight (25%) believed that no restrictions applied after a TIA. Driving restrictions for stroke with complete recovery of 1 month for domestic and 1 year for commercial license were correctly answered by 56 (29%) and 117 (71%); only 23 (12%) thought that no restrictions applied. There were no significant variations in knowledge attributable to seniority, formal instruction of driving regulations or working with stroke patients.

Conclusions:
Doctors have limited knowledge of driving restrictions after TIA or minor stroke, which presents significant public safety and medico-legal risks. Innovative methods are required to improve the acquisition and retention this knowledge in front line doctors.
Abstract 3685: Collagen Isoform Distribution Patterns In Cerebral Vessels In CADASIL
Authors: Dong Hairong , Blaivas Mila , Wang Michael
Published: July 2021

Objective:
Arteries in CADASIL are susceptible to fibrosis and smooth muscle cell loss. The molecular components underlying vascular remodeling are not well characterized. The purpose of this study was to test the hypothesis that distinct collagen isoforms accumulation in the media of the cerebral vessels in CADASIL.

Methods:
Brain sections from six CADASIL patients with mutations in NOTCH3 were compared to age matched controls. Expression of Type I, II, III, IV, V, VI, and IX collagen were studied by immunohistochemistry.

Results:
We identified a consistent increase of Type I, III, IV, and VI collagen content in the large and small vessels of CADASIL brains relative to controls. We did not find Type II, V, IX collagen in the brain. Within leptomeningeal arteries where we could definitively visualize the three layers of each vessel, we found that Type I, III, IV and VI collagens were found in heterogeneous locations. Types I and III collagen was mostly transmural or adventitial/medial. Type IV was strictly intimal/medial. Type VI was largely adventitial/medial. The most significant difference between CADASIL and controls was the appearance of all four collagen types in the vascular media. Within the thickened penetrating arteries of CADASIL patients, all four collagens extended through most of the arterial wall. Finally, we observed increased staining of capillaries in CADASIL for Type I, IV, and VI.

Conclusion:
In CADASIL, brain vascular collagen subtypes are increased in multiple layers of both large and small vessels, with the most dramatic changes in the tunica media and thickened small penetrating vessels. These studies suggest that collagen accumulation in the vascular media may play a pathogenic role in small vessel disease.
Abstract 3718: Specialized Nursing Team for Stroke Education Increases Compliance
Authors: Christi Amanda G
Published: July 2021

Background and Purpose:
Primary Stroke Center Certification through the Joint Commission requires specific education to patients who have sustained a stroke. Low rates of completed education were noted for stroke patients during our needs assessment. Issues with compliance included ambiguous admission diagnoses, lack of time for registered nurses to complete the education, and a deficiency in knowledge related to the Joint Commission’s certification standards. The purpose of this study was to assess the impact of a nursing stroke education team on the compliance rates of stroke education.

Methods:
A group of NIHSS certified nurses volunteered to be on the team, named the Team About Stroke Education and Research (TASER). These nurses received in-depth education on stroke pathophysiology and treatments, adult learning theories, and the requirements for stroke certification through the Joint Commission. By using concurrent auditing and daily rounds, TASER nurses tracked possible stroke patients within the facility and were responsible for completing the educational requirements and related documentation. A goal of 85% of completed education was set. Data was collected using retrospective audits.

Results:
During the six months prior to the TASER initiation, the percentage of inpatients with a discharge diagnosis of stroke who received required education was at 39.1% (9/23). During the six months after the TASER initiation, that percentage of patients who required education increased to 82.6% (19/23). TASER nurses identified 139 potential stroke patients in that 6 month period and educated a total of 68 patients, regardless of their final diagnosis, disposition, or destination.

Conclusions:
The TASER program showed improvements in compliance of educational requirements. Although not at the goal of 85%, further education and additional TASER nurses may increase our numbers. Future testing of the retention of the education provided may be warranted.
Abstract 3866: The Inhibition of WWP-1 and Activation of AMPKa2 Are Important Mediators of Ischemic Stroke
Authors: Ahn Yong-Joo , Lee Jung Ok , Hwang Seo-Kyoung , Kim Hyeon Soo , Liao James K. , Kim Hyung-Hwan
Published: July 2021

Background:
Tuberous sclerosis complex (TSC) and Mammalian target of rapamycin (mTOR) mediate various functions such as cell survival, obesity, and cellular responses in injury. However, the signaling mechanism linking focal cerebral ischemia is unknown. Because inhibition of the mTOR signaling pathway contributes to the pathogenesis of ischemic stroke, we hypothesize that inhibition of WW domain protein 1 (WWP-1) and activation of AMPKα2 mediate neuroprotection effect
via
WWP-1/AMPKα2/TSC/mTOR/S6 signaling pathways.

Methods:
To investigate whether the inhibition of WWP-1 and activation of AMPKα2 could exert neuroprotective effect via mTOR signaling pathways, we performed transient focal cerebral ischemia. Wild-type and TSC2
+−
mice (20-22g) were administered either vehicle or rapamycin (5 mg/kg, i.p., 1d and 5d), before MCAO. After 2 hrs of MCAO followed by 22 hrs of reperfusion, Infarct size was determined with TTC staining and protein levels were assessed in ischemic core and contralateral (non-ischemic core) hemisphere region.

Results:
Compare to vehicle mice, mTOR/S6 level was decreased in ischemic brain region during ischemia (0.5, 1, 2h MCAO). After reperfusion (after 2h MCAO), phospho-S6 in mice brain was quickly over-expressed. Acute administration of rapamycin had no effect on cerebral infarct size in WT mice but chronic administration of rapamycin exhibited significantly increased infarct size and higher NDS following MCAO. Compare to vehicle mice, TSC2
+−
mice showed increased mTOR/S6 level in brain and reduced cerebral infarct size (64.2 ± 5.96;
n
=7
vs
92.6 ± 6.08,
n
=7,
p
<0.01).

Conclusions:
These findings indicate that the inhibition of WWP-1 and activation of AMPKα2 reduced infarct size via TSC2/mTOR/S6 signal transduction in focal cerebral ischemia. These results suggest that inhibition of WWP-1 and activation of AMPKα2 may have therapeutic benefits in ischemic stroke.
Abstract 107: Early Change in Ferumoxytol-Enhanced Magnetic Resonance Imaging Signal Suggests Unstable Human Cerebral Aneurysm. A Pilot Study
Authors: Hasan David M , hesitad donald
Published: July 2021

Background:
Imaging with magnetic resonance imaging (MRI) 72 hours after infusion of ferumoxytol demonstrated maximal uptake by macrophages in the wall of human cerebral aneurysms. The clinical significance of early (i.e. within the first 24 hours) uptake of ferumoxytol by macrophages in the wall of human cerebral aneurysms is not clear. The purpose of this study was to determine whether early uptake of ferumoxytol which may indicate inflammation, suggests unstable cerebral aneurysm.

Methods:
30 unruptured aneurysms in 22 patients were imaged with MRI 24 hours after infusion of ferumoxytol. Eighteen aneurysms were also imaged 72 hours after infusion of ferumoxytol. Aneurysm dome tissue was collected from four patients with early MRI signal changes, five patients with late signal changes, and five other patients with ruptured aneurysms. The tissue was immunostained for expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal-prostaglandin-E2 synthase-1 (mPGES-1) and macrophages.

Findings:
In 23% (7/30) of aneurysms, there was pronounced early uptake of ferumoxytol. Four aneurysms were clipped. The remaining three aneurysms which were managed conservatively with observation, all ruptured within six months. In 89% (16/18) of aneurysms, there was pronounced uptake of ferumoxytol at 72 hours. Nine aneurysms were surgically clipped and nine were managed conservatively; none ruptured or increased in size in six months. With immunostaining, expression of COX-2, mPGES-1, and macrophages was similar in unruptured aneurysms with early uptake of ferumoxytol and ruptured aneurysms. Expression of these inflammatory molecules was significantly higher in aneurysms with early uptake of ferumoxytol than in aneurysms with late uptake.

Interpretation:
Uptake of ferumoxytol in aneurysm walls within the first 24 hours strongly suggests aneurysm instability and probability of rupture within six months, and may warrant intervention. Larger clinical studies are indicated to validate this preliminary observation.
Abstract 121: Early Mobilization of Ischemic Stroke Patients post Intravenous Tissue Plasminogen Activator
Authors: Davis Olivia , Mooney Lesia , Dinkins Maryane , Freeman William D , Arnold Scott
Published: July 2021

Background/Purpose:
Research about mobilization of patients who receive IV-tPA is scarce. Patients are routinely kept on bed rest for 24-48 hours after tPA for monitoring despite a lack of evidence justifying this lengthy immobilization. Several stroke rehabilitation studies report mobilizing patients within 24 hours of stroke. However, none of these studies included patients who received tPA and there are no published recommendations for safe timeframes for initiating mobilization of these patients. We completed a preliminary study to assess the hypothesis that adverse safety outcomes of early mobilization of this patient population are minor.

Methods:
We conducted a study between June 2011 and July 2012 involving early mobilization (i.e. PT/OT between 13 and 24 hours) of patients administered tPA. A safety screen was performed before mobilization occurred to verify hemodynamic stability of patients. Mobilization may have included sitting, standing, transferring to a chair, and ambulation.

Results:
Nearly 97% (30/31) of patients provided consent (12 female, 18 male; mean age: 66.8, range: 32-89; mean admission NIHSS 5.37, range 0 - 27). All consented patients were screened and 23/30 were mobilized without adverse response. Eighty-six percent (70/81) of activity events had no adverse response. The adverse events that were observed were transient and minor: 2 subjects reported “dizziness” (without a corresponding drop in BP), 3 subjects had an increase in DBP to > 105 (with resting DBPs as follows: 93, 104, and 62 mmHg), 1 subject had a HR > 100 bpm (resting HR was 96 bpm), and 1 had new-onset of neurological signs (transient L hemiparesis that resolved within an hour). Analysis is currently being performed Biostatistician.

Conclusion:
Early mobilization of patients post ischemic stroke 13-24 hours after IV-tPA infusion appears safe for 76.7% of patients and during 86.4% of activity events. In conclusion, adverse responses were largely minor with no sustained worsening of neurologic deficits. Study investigators recommend larger-powered studies for validation of safety findings to develop evidenced-based guidelines for early mobilization of this patient population.
Abstract 124: Post-acute Care Disposition To Home Or Acute Rehabilitation Helps Determine Favorable Clinical Outcome In The SENTIS Trial.
Authors: Belagaje Samir R , Zander Kay , Thackeray Lisa , Gupta Rishi
Published: July 2021

Intro:
A person with stroke has improved outcomes with post-acute care in an inpatient rehabilitation facility (IRF) or at home compared to those who are discharged to a skilled nursing facility (SNF). However, this research was conducted in an era before acute stroke treatment was fully developed and implemented. In this analysis of a recently completed acute intervention trial, we hypothesize that subjects with similar severity of strokes will have better 90 day outcomes if they are discharged to a IRF or home compared to a SNF.

Methods:
Using the data from SENTIS, a prospective, multi-center single-blind, randomized trial of use of NeuroFlo technology compared to standard acute stroke therapy, patient demographics, day 4 National Institutes of Health Stroke Scores (NIHSS), and 90 day modified Rankin scores (mRS) was obtained. Severity of stroke was classfied in 3 groups based on NIHSS: less than 8, 8-13, 14+. Disposition following acute hospital care was classified as home, IRF and SNF. A favorable outcome was defined as 90 day mRS ≤ 2. For each stroke severity class, the effect of each disposition on a favorable outcome was calculated.

Results:
A total of 292 patients were analyzed with a mean age of 65±14 with presenting NIHSS of < 8 in 94/297(31.6%), NIHSS 8-13 in 118/297(39.7%) and 14+ in 85/297(28.6%) of patients. Regardless of day 4 NIHSS, only 2 out of 28 (7.1%) patients who were discharged to SNF achieved a 90 day mRS ≤2, compared to 60/153 (39.2%) in the IRF group (OR 8.02 95%CI[1.83-35.11], p=0.0057). Table 1 shows the distribution of outcomes by post-acute care disposition and day 4 NIHSS.

Conclusions:
The day 4 NIHSS had an inverse relationship with the likelihood of a favorable outome. Subjects who were discharged home or to an IRF were significantly more likely to have a favorable outcome compared to those who were discharged to a SNF. This analysis supports prior data stating that discharge disposition plays a role in determining outcomes.
Abstract 133: Magnetic Resonance Imaging Based Transient Ischemic Attack Triage In The Emergency Department Is Feasible And Safe
Authors: Vora Nirali , Tung Christie E , Mlynash Michael , Tai Waimei , Garcia Madelleine , Kemp Stephanie , Albers Gregory W , Olivot Jean-Marc
Published: July 2021

Objective:
To evaluate the safety and feasibility of a magnetic resonance imaging (MRI) based transient ischemic attack (TIA) triage pathway in the emergency department (ED). We hypothesized that an MRI based triage pathway in an academic setting would be feasible and associated with a low rate of stroke recurrence.

Methods:
From January 2010 to May 2011, consecutive patients assessed in our institution’s ED for suspicion of TIA were evaluated by a neurologist and underwent MRI with diffusion weighted imaging (DWI) and MRA of the head and neck within 12 hours per radiology department convention. By protocol, the neurologist recommended admission for patients with restricted diffusion on MRI, symptomatic vessel stenosis, or per clinical judgment. Final diagnosis was adjudicated by the treating neurologist at the time of discharge as definite or possible transient cerebrovascular event, or a non-cerebrovascular event. Stroke recurrence was evaluated at 1 week, 3 months, and 1 year with a telephone interview.

Results:
One hundred and twenty nine patients were enrolled with a mean age of 69 years (+/-16.8) and median ABCD
2
of 3 (IQR 3-4). Final diagnosis was definite transient cerebrovascular event in 77 (59.7%), possible in 21 (16.3%), and other in 31 (24%). At the time of triage, 112 (92%) patients underwent brain MRI in the ED after a median delay of 8.2 hours (IQR 4.8-14.7) from arrival and 15.7 hours (IQR 9.9-22.8) from symptom onset. No patients experienced a recurrent stroke before imaging. Twenty two (19.6%) patients had a positive DWI and 9 (8%) had a symptomatic vessel stenosis. All but two patients with a positive DWI or MRA were admitted. In total, 46 of the 129 (35.7%) patients were hospitalized and one (2.2%) had a recurrent stroke after 90 days. Of 83 patients discharged from the ED, one (1.2%) had a minor stroke at one week. This patient’s baseline MRI was DWI negative and MRA was without stenosis. Altogether, among 98 patients with a final diagnosis of possible or definite transient cerebrovascular event, the rate of recurrent stroke was 1.03% at 7 and 90 days, and 2.2% at one year.

Conclusion:
Acute evaluation of TIA using an MRI based triage approach is feasible and associated with a low rate of recurrent stroke.
Abstract 150: Protein Nitration Impairs Myogenic Reactivity of Cerebral Vessels in Both Ischemic & Non-ischemic Hemispheres
Authors: Coucha Maha M , Li Weiguo , Fagan Susan C , Ergul Adviye
Published: July 2021

Cerebrovascular autoregulation is 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 (IS) side. Yet the behavior of vessels in nonischemic (NIS) side is still unexplored.

Hypothesis:
I/R injury impairs myogenic tone of vessels in both IS & NIS hemispheres via increased peroxynitrite (ONOO
-
) generation.

Methods:
Male Wistar rats (n=8) were subjected to sham or 30 min middle cerebral artery occlusion (MCAO)/45 min reperfusion. Rats were administered saline, ONOO
-
decomposition catalyst FeTPPs (20 mg/kg) or nitration inhibitor epicatechin (30mg/kg) at reperfusion. In another set of animals, MCA isolated from control rats were exposed to ex-vivo hypoxia with and without gp-91 tat (NADPH oxidase inhibitor 1μM), L-NAME (0.3 mM) and Catalase (1000 u/ml) during reoxygenation. The tone of MCAs across the pressure range was measured using pressurized arteriograph. Nitrotyrosine levels in MCAs from both hemispheres were evaluated using immunoblotting.

Results:
I/R injury impaired myogenic tone of vessels in both IS & NIS hemispheres albeit to a different degree. Vessels exposed to ex-vivo hypoxia experienced similar loss of myogenic tone. Inhibiting ONOO
-
by FeTPPs and nitration by epicatechin restored myogenic tone of vessels from both hemispheres back to normal, while inhibiting hydrogen peroxide had no effect. Nitration was significantly increased in both IS (**p<0.01) & NIS hemispheres (*<p0.05) vs sham. Treatment with epicatechin efficiently reduced the extent of nitration back to normal.

Conclusion:
These results support our hypothesis that I/R injury impairs myogenic tone in BOTH IS and NIS hemispheres and protein nitration due to increased ONOO
-
production is one of the underlying mechanisms of loss of tone.(† p<0.001, * p< 0.05 vs Sham, # p<0.001 vs IS, *p<0.05,***p<0.001 vs NIS)
Abstract 154: Protection from Transient Focal Cerebral Ischemia by Transfusion of Polynitroxylated Pegylated Hemoglobin
Authors: Zhang Jian , Cao Suyi , Ma Li , Hsia Carleton J , Koehler Raymond C
Published: July 2021

Polynitroxylation of hemoglobin (Hb) confers superoxide dismutase and catalase mimetic activity and can protect neurons from native Hb and glutamate. Here, we determined if transfusion of polynitroxylated pegylated Hb (PNPH) is protective in the rat filament model of 2 h of middle cerebral artery occlusion (MCAO). Transfusion of 10 ml/kg of PNPH at 20 min of MCAO reduced the median infarct volume in cerebral cortex from 40% (37-47% interquartile range; n=10) in controls to 3% (0-7%; n=10; P<0.001) with PNPH and in striatum from 78% (66-88%) to 34% (0-37%; P<0.001). The therapeutic window was evaluated in a second experiment. Compared to the control median hemispheric infarct volume of 22% (13-34%; n=15), infarct volume was reduced to 7% (3-13%; n=14; P<0.05) when PNPH was transfused at 4 h after MCAO (2 h of reperfusion) but not significantly when transfused at 6 h (8%; 3-35%; n=14) or at 8 h (12%; 10-25%; n=14) after MCAO. To determine whether PNPH might act by promoting vasodilation, pial arteriolar diameter in the distal MCA border region was measured in closed cranial windows during MCAO. With no transfusion, MCAO induced an initial dilation (36±5%; ±SD; n=8) that subsided by 2 h (5±11%). With PNPH transfusion at 20 min of MCAO, the initial dilation (31±8%; n=7) was better maintained at 2 h (21±11%; P<0.02). To determine whether delaying PNPH transfusion until 90 min of MCAO would improve penumbral perfusion, laser-Doppler flow (LDF) was measured in the ischemic border region where the reduction in LDF was less severe than in the core. LDF significantly increased from 48±18% of the pre-ischemic baseline to 67±21% (P<0.005). Thus, PNPH transfusion has a significant therapeutic window for protection from transient MCAO and may act, in part, by stabilizing vascular function and improving collateral blood flow.
Abstract 2: Thrombolytic Therapy and Survival for Medicare Beneficiaries with Acute Ischemic Stroke
Authors: Tong Xin , Yang Quanhe , George Mary G
Published: July 2021

Background:
Thrombolytic therapy (tPA) is the only fibrinolytic agent used in the treatment of acute ischemic stroke. It is recommended due to its ability to achieve early reperfusion and improve neurologic outcomes. This study assesses the survival outcome of tPA use among Medicare beneficiaries with acute ischemic stroke in the Paul Coverdell National Acute Stroke Registry (PCNASR).

Methods:
A total of 24,625 patients with a clinical diagnosis of acute ischemic stroke enrolled in the PCNASR from January 2008-December 2010 were linked to MEDPAR 2008-2010 database. Patients with documented reasons for not giving tPA (intravenous and/or intra-arterial) were excluded. A propensity score 1:1 matched-pair sample was created to assess survival among patients receiving tPA and not receiving tPA. The probability of survival was estimated by the Kaplan-Meier method and was compared by the test described by Klein and Moeschberger. The hazard ratio was obtained by using Cox proportional hazard regression model stratified on matched pairs.

Results:
A total of 3370 matched patients were selected based on age, gender, race, National Institutes of Health Stroke Scale (NIHSS), medical history of atrial fibrillation, diabetes, heart failure, smoking, prior stroke and myocardial infarction or coronary disease. Patients who received tPA had better survival than patients with no tPA (p=0.0109). The adjusted hazard ratios were 0.84, [0.72, 0.98], 0.86 [0.75, 0.99] and 0.84 [0.74, 0.96] for 30-days, 90-days and one-year survival, respectively. Limitation: In the absence of direct identifiers, the linked datasets might contain possible incorrect information.

Conclusion:
This analysis found approximately 15% improved short and long term survival among patients receiving tPA for acute ischemic stroke in a non-clinical trial setting.
Abstract 205: Risk of Intracranial Hemorrhage with Protease-activated Receptor-1 Antagonists
Authors: Lee Meng , Saver Jeffrey L , Hong Keun-Sik , Wu Hsiu-Chuan , Ovbiagele Bruce
Published: July 2021

Background:
Recent clinical trial data suggest that protease-activated receptor-1 (PAR-1) antagonists may increase the risk of intracranial hemorrhage (ICH). Our objective was to investigate the qualitative and quantitative risk of ICH in patients receiving PAR-1 antagonist therapy.

Methods:
Pubmed and EMBASE from 1966 to May 2012 were searched to identify relevant studies. We included randomized controlled trials that included a comparison of PAR-1 antagonist with placebo, and in which the total number of patients and ICH events were reported separately for active treatment and control groups. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using random-effects models. Between-study heterogeneity was assessed using the
I
2
statistic.

Results:
In 9 PAR-1 antagonist trials with 42, 000 patients with a history of thrombotic vascular disease or acute coronary syndrome, PAR-1 antagonist treatment was associated with increased risk of ICH (0.59% vs. 0.30%; RR 1.98, 95% CI 1.46 to 2.68, P < 0.00001) (Figure). There was no heterogeneity across trials (P=0.84, I
2
=0%), PAR-1 antagonist agent (P=0.52), treatment duration (P=0.38), or trial-qualifying event (P=0.59). Risk of death from any cause or a cardiovascular cause did not differ between active treatment and control groups.

Conclusion:
This meta-analysis showed that patients with a history of thrombotic vascular disease or acute coronary syndrome treated with PAR-1 antagonists are at higher risk of experiencing ICH, a dreaded form of stroke, associated with high mortality and greater loss of health over a survivor’s lifetime than ischemic stroke.
Abstract 207: Vorapaxar in Patients with Prior Ischemic Stroke: Primary Results from the Stroke Cohort of the Multinational TRA 2°P-TIMI 50 Trial
Authors: Morrow David A , Alberts Mark , Mohr Jay P , Ameriso Sebastian , Bonaca Marc , Goto Shinya , Hankey Graeme J , Murphy Sabina , Scirica Benjamin , Teal Philip , Braunwald Eugene
Published: July 2021

Vorapaxar is an antiplatelet agent that potently inhibits thrombin-mediated activation of the platelet protease-activated receptor (PAR)-1. Phase 2 trials of vorapaxar suggested efficacy with acceptable safety in patients with ischemic stroke.

Methods:
TRA 2°P–TIMI 50 was a multinational, randomized, double-blinded, placebo-controlled trial of 26449 patients with a history of atherothrombosis randomized to vorapaxar (2.5 mg daily) or matching placebo added to standard therapy, including antiplatelet agents. Patients who qualified with stroke (N=4883) had a history of ischemic stroke in the prior 2 wks to 12 mo. The first efficacy endpoint was the composite of cardiovascular (CV) death, MI, or stroke. After 2 years, the Data and Safety Monitoring Board recommended discontinuation of study treatment in patients with prior stroke.

Results:
The qualifying stroke was classified as large vessel in 35%, small vessel in 47%, and other in 18%. Background therapy included aspirin in 81%, clopidogrel in 22%, and dipyridamole in 19%. In the stroke cohort, the 3-year rate of CV death, MI, or stroke was not reduced with vorapaxar vs. placebo (13.0% vs. 11.7%, HR 1.03; 95% CI 0.85-1.25), including recurrent ischemic stroke (HR 0.99; 95% CI 0.78-1.25). There were no statistically significant differences in the effect of vorapaxar based on the type or timing of the qualifying stroke, and a borderline interaction based on co-administration of clopidogrel (Figure) The rate of intracranial hemorrhage (ICH) at 3 years was 2.5% with vorapaxar vs. 1.0% with placebo (HR 2.52; 95% CI 1.46-4.36).

Conclusions:
In patients with prior stroke receiving standard antiplatelet therapy, adding vorapaxar increased the risk of ICH without a reduction in the primary efficacy endpoint or ischemic stroke. These findings add to the accumulating evidence establishing important risks with combination antiplatelet therapy in patients with prior stroke.
Abstract 214: The Vascular Niche in Adult Mouse Brain After Stroke - Confocal Imaging of Whole Mount SVZ
Authors: Zhang Rui Lan , Chopp Michael , Roberts Cynthia , Nejad-Davarani Siamak , Zhang Li , Wei Min , Wang Xinli , Liu Xianshuang , Zhang Zheng Gang
Published: July 2021

Stroke induces angiogenesis in the peri-infarct region. It is not known whether angiogenesis occurs in the subventricular zone (SVZ) of the lateral ventricle after stroke. The SVZ is a neural stem cell niche containing vascular plexus that supports adult neurogenesis. We characterized longitudinal changes of vascular structures in the SVZ niche after stroke using whole mounts, an organotypic preparation of the SVZ in which the 3D cell-vessel relationships are preserved.

Adult mice were subjected to middle cerebral artery occlusion (MCAO). The vascular architectures within the 50 μm thick SVZ of immunostained whole mounts were imaged by 3D confocal microscopy. In non-MCAO mice (n=4), 2±0.2% of endothelial cells were proliferative (BrdU+/CD31+). Blood vessels in this niche constituted 2.6±0.01% of the total volume with 75±17 vascular branches. However, 7 and 14 days after MCAO, proliferated endothelial cells significantly (p<0.05) increased to 12±1% (n=5) and 15±1 % (n=5), respectively, which was followed by substantial increases in vascular volume at 14 (4.2±0.01%, n=3), 30 (4.9±0.05%, n=3), and 90 (5.7±0.01%, n=3) days, but not at 7 days after MCAO. Moreover, vascular branches increased significantly to 156±27 and 216±8 at 30 and 90 days, respectively, but not at 14 days. Interestingly, we detected increases in the number of string-like vessels starting at 14 days (731±79/mm
3
vs 476±41/mm
3
in control) which increased and persisted at 30 (1,824±255/mm
3
) and 90 (1,748±204/mm
3
) days after MCAO. These string-like vessels were not perfused by plasma. String vessels increase during embryonic angiogenesis. Collectively, these data indicate that stroke induces angiogenesis in the SVZ, which lasts at least 90 days after stroke. Moreover, stroke significantly increased neural stem cells (BrdU
+
/GFAP
+
, 13±3%, 15±3%, and 11±4% at 7, 14, and 90 days, respectively, vs 6±1% in control) and newborn neurons (BrdU
+
/DCX
+
, 14±2% and 12±2.0% at 7 and 14 days, respectively, vs 4±1% in control). Neural stem cells at the ventricular surface extended their processes to the blood vessels in the SVZ.

Our data indicate that stroke induces angiogenesis in the SVZ, which is associated with stroke-induced neurogenesis.
Abstract 28: Effects of Self-Esteem, Optimism, and Perceived Control on Depression: Testing Dyadic Dynamics in Stroke Survivor-Spouse Dyads
Authors: Chung Misook L , Bakas Tamilyn , Plue Laurie D , Williams Linda S
Published: July 2021

Background:
Depression is common in stoke survivors and their caregivers. Given the interdependent relationship among the members of dyads in post-stroke management, improving depression in dyads may depend on their partner’s characteristics. Self-esteem, optimism, and perceived control, all known to be associated with depression in an individual, may also contribute to their partner’s depression. The purpose of this study was to examine whether an individual’s self-esteem, optimism and perceived control predict their own, as well as their partner’s depression.

Methods:
A total of 112 ischemic stroke survivor-spouse dyads completed surveys in which depression, self-esteem, optimism, and perceived control were assessed using the Patient Health Questionnaire, the Rosenberg Self-esteem Scale, the Revised Life Orientation Test, and the Sense of Control Scale. Multilevel modeling, actor-partner interdependence model (APIM) regression with distinguishable dyad was used to determine influences on depression within the dyad. In APIM, actor effect is the impact of a person’s factors on their own depression and partner effect is the impact of a person’s factors on their partner’s depression.

Results:
As shown in Figure1, individuals with lower self-esteem, optimism, and perceived control had higher level of depression. Spouses who had stroke survivors with low self-esteem had higher levels of depression. Stroke survivors who had spouses with lower self-esteem and optimism had higher levels of depression.

Conclusion:
Stroke survivor self-esteem and spouse self-esteem and optimism influenced their partner’s depression. These findings suggest that dyadic intervention is needed to improve depression for the dyads and that depressed stroke survivors may benefit from interventions that improve spousal self-esteem and optimism.
Abstract 33: PFO in Cryptogenic Stroke: An Analysis of “High Risk” Features on Transesophageal Echocardiography in the Risk of Paradoxical Embolism Database
Authors: Wessler Benjamin , Thaler David E , Di Tullio Marco R , Ruthazer Robin , Weimar Christian , Mas Jean-Louis , Serena Joaquín , Di Angelantonio Emanuele , Donovan Jennifer S , Elkind Mitchell S , Griffith John , Jaigobin Cheryl , Mattle Heinrich P , Michel Patrik , Mono Marie-Louise , Nedeltchev Krassen , Papetti Federica , Kent David M
Published: July 2021

Introduction:
A patent foramen ovale (PFO) discovered in the setting of a cryptogenic stroke (CS) may be stroke-related or incidental. We have developed a score to stratify CS patients according to the probability that the event is attributable to a PFO (the Risk of Paradoxical Embolism (RoPE) Score), based on easily obtainable clinical and neuroradiological (but not transesophageal echocardiographic (TEE) variables. In this study, we examined whether putative “high risk” TEE features - shunt size, presence of a hypermobile septum, and presence of a right-to-left shunt at rest - vary across RoPE Score strata.

Methods and Results:
The RoPE Study combined existing cohort studies to create a pooled database of patients with CS and PFO. We dichotomized patients into groups and examined whether putative high risk TEE features are seen more frequently in those with “probable stroke-related” PFOs (RoPE Score of >6, estimated PFO attributable fraction 72-99%, n=637) than in those with lower RoPE Scores (<6, PFO attributable fraction 0-71%, n=657). None of the TEE features differed between the groups (large physiologic size, p=0.53; hypermobile septum, p=0.44; shunt at rest, p=0.11). Extensive additional exploratory analyses did not reveal any consistent associations between different RoPE Score strata and presumptive high risk echocardiographic features.

Conclusion:
We found no evidence that proposed TEE markers for “high risk” PFOs correlate with the estimated likelihood that a PFO is related to an index CS. Additional imaging tools or better standardization of imaging techniques are needed to determine whether specific anatomic features are associated with whether a discovered PFO is likely to be related to CS.
Abstract 34: Improvement In Etiological Identification In Tia And Minor Stroke Using The Causative Classification Of Stroke.
Authors: Desai Jamsheed A , Abuzinadah Ahmad , Imoukhuede Oje , Modi Jayesh , Bernbaum Manya L , Coutts Shelagh B
Published: July 2021

Background:
classification of Transient Ischemic attacks (TIA) and minor stroke is challenging, as there is no classification systems developed specifically for the TIA and minor stroke patient population.

Hypothesis:
We hypothesize that the newly developed Causative Classification System (CCS) and the Atherosclerosis Small Vessel Disease Cardiac Source Other Source (ASCO) classification would reduce the proportion of patients classified as cause undetermined compared with The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification in a large prospectively evaluated TIA and Minor stroke population.

Methods:
Using published algorithms for TOAST, CCS, and ASCO, a single rater classified the etiology in patients presenting with a high-risk TIA (weakness or speech disturbance lasting ≥ 5minutes) or minor ischemic stroke (National Institute of Health Stroke Scale score ≤ 3) who underwent CT/CTA and subsequent MRI as part of the CATCH study.

Results:
419 patients with TIA or Minor stroke were classified using TOAST, CCS, and ASCO. The proportion of patients with an undetermined etiology was 51.3% (215/419) with TOAST. This was significantly reduced by both CCS 36% (151/419, p< 0.001) and ASCO 41% (172/419, p< 0.001). CCS was also less likely to have an undetermined etiology as compared to ASCO (36% versus 41%, p = 0.024). When compared with TOAST, there was a 23.9% (95%CI:18.1- 29.7, P< 0.001) and 17.4% (10.1- 24.7, P< 0.001) reduction in the proportion of patients assigned to the undetermined group using CCS and ASCO respectively. The 8.5 % reduction in the undetermined group between CCS and ASCO was also statistically different P=0.031). Compared with ASCO1, CCS increased the assignment of patients to large artery disease (relative increase 7.4% {4.3-10.4}, P< 0.001) and Cardio-embolism/cardio-aortic categories (relative increase 8.1% {4.6-11.5}, P< 0.001).

Conclusions:
Both CCS and ASCO were superior to TOAST in assigning fewer patients to an undetermined etiology category. CCS was superior to ASCO at reducing the proportion of patients with undetermined etiology. This was largely driven by increased assignment in the large artery and Cardio-aorto embolic categories.
Abstract 4: Variation and Temporal Trends in the Characteristics of US Hospitals Treating Acute Ischemic Stroke Patients with IV-tPA: Findings from GWTG-Stroke
Authors: Schwamm Lee H , Ali Syed F , Reeves Mathew J , Smith Eric E , Saver Jeffrey L , Messe Steven , Bhatt Deepak L , Grau-Sepulveda Maria V , Peterson Eric D , Fonarow Gregg C
Published: July 2021

Introduction:
Utilization of IV tPA is challenging for many hospitals. Using data from the national Get With The Guidelines-Stroke program, we analyzed changes over time in the characteristics of the hospitals that treated patients with tPA.

Methods:
We analyzed patient-level data from 2003-2011 at 1600 GWTG hospitals that joined the program at any time during the study period and admitted any acute ischemic stroke (AIS) patients arriving ≤ 2 hr of onset and eligible for tPA. Descriptive trends by time were analyzed by chi-square or Wilcoxon test for continuous data.

Results:
IV tPA was given within 3 hr at 1394 sites to 50,798/ 75,115 (67.6%) eligible AIS patients arriving ≤ 2 hr; 206 (14.8%) sites had a least one eligible patients but no tPA use. IV tPA treatment rates varied substantially across hospitals (median 61.2%, range 0-100%), with > 200 hospitals providing tPA < 10% of the time (Figure). Over time, more patients and a larger proportion of patients were treated at smaller (median bed size 407 vs. 372, p< 0.001), non-academic, Southern hospitals, and those with lower annualized average ischemic stroke volumes (252.4 vs. 235.2, p< 0.001) (Table). While more than half of all tPA patients were treated at Primary Stroke Centers, this proportion did not change over time. The proportion of patients treated at high volume tPA treatment sites (average > 20/year) increased over time (31.9 vs. 34.5, p< 0.007).

Conclusion:
Over the past decade, while primary stroke centers still account for more than half of all treatments, tPA has been increasingly delivered in smaller, non-academic hospitals. These data support the continued emphasis on stroke team building and systems of care at US hospitals.