bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract T P170: Risk Stratification in Acute Ischemic Stroke by Transcranial Doppler in a Multiethnic Population: Role of Microembolic Signal
Authors: Bazan Rodrigo , Braga Gabriel P , Bazan Silméia G , Hueb João C , Leite João P , Pontes-Neto Octávio M
Published: July 2021

Background:
The role of microembolic signal (MES) detected by transcranial Doppler sonography in the acute phase of a stroke remains controversial in the medical literature. The prevalence of MES in the various sources of arterial brain embolism in patients in developing countries has been poorly studied. We investigated the prevalence of MES and whether MES detection is of proven use for risk stratification in the Brazilian population

Methods:
This was a transversal study with 45 ischemic stroke patients in acute phase at the Stroke Unit in a Brazilian hospital. All patients underwent monitoring of the middle cerebral arteries by transcranial doppler for at least 30 minutes. The examiner who conducted the monitoring was unaware of the risk stratification of the patient(single blinded). Then the record of the examination was independently analyzed by two neurologists to identify the MES. Prior to monitoring, risk stratification was carried out for all patients by complementary examinations. The independent variables were: age, NIHSS at admission, time of ictus, symptomatic carotid disease (stenosis > 60%), atrial fibrillation, intracranial stenosis, diseases of small arteries and other cardioembolic sources. The outcome was the presence or absence of MES with independent variables. The relationship between admission variables and MES was analyzed by Fisher’s Exact Test and logistic regression to estimate the odds ratio with significance defined as p<0.05.

Results:
The prevalence of MES was 10%. A significant correlation was found between ictus < 24 hours before transcranial Doppler examination (p=0.04; OR=5.0) and symptomatic carotid disease (p=0.03; OR=15.6) with presence of MES. There was no statistical correlation between age (p=1.0), intracranial stenosis (p=1.0), atrial fibrillation (p=0.55), diseases of small arteries (p=0.56), other cardioembolic sources (p=0.55), and the association with atrial fibrillation and symptomatic carotid disease (p=1.0).

Conclusions:
MES detection showed higher correlation with symptomatic carotid disease and the precocity of monitoring in relation to time of ictus too. There was no relationship found between cardioembolic source and atrial fibrillation.
Abstract T P231: Does Intraventricular Hemorrhage Lead to a Normal Pressure Hydrocephalus-Like Syndrome?
Authors: Kruger Andrew J , Flaherty Matthew , Sekar Padmini , Haverbusch Mary , Moomaw Charles J , Martini Sharyl , Ferioli Simona , Ringer Andrew J , Kissela Brett M , Kleindorfer Dawn O , Broderick Joseph P , Woo Daniel
Published: July 2021

Background:
Intracerebral hemorrhage (ICH) has the highest short and long-term morbidity and mortality rates of stroke subtypes. While increased intracranial pressure due to the presence of intraventricular hemorrhage (IVH) may relate to early poor outcomes, the mechanism of reduced 3-month outcome with IVH is unclear. We hypothesized that IVH may cause symptoms similar to normal pressure hydrocephalus (NPH), specifically urinary incontinence and gait disturbance.

Methods:
We used interviewed cases from the Genetic and Environmental Risk Factors for Hemorrhagic Stroke Study (7/1/08-12/31/12) that had 3-month follow-ups available. CT images were analyzed for ICH volume and location, and IVH presence and volume. Incontinence and dysmobility were defined by Barthel Index at 3 months. We chose a Barthel Index score of bladder less than 10 and mobility less than 15 to define incontinence and dysmobility, respectively. Multivariate analysis was used to assess independent risk factors for incontinence and dysmobility. ICH and IVH volumes were log transformed because of non-normal distributions.

Results:
Barthel Index was recorded for 308 ICH subjects, of whom 106 (34.4%) had IVH. Presence of IVH was independently associated with both incontinence (OR 2.7; 95% CI 1.4-5.2; p=.003) and dysmobility (OR 2.5; 95% CI 1.4-4.8; p=.003). The Table shows that increasing IVH volume was also independently associated with both incontinence and dysmobility after controlling for ICH location, ICH volume, age, baseline mRS, and admission GCS.

Conclusion:
Our data show that patients with IVH after ICH are at an increased risk for developing the NPH-like symptoms of incontinence and dysmobility. This may explain the worse long-term outcomes of patients who survive ICH with IVH than those who had ICH alone. Future studies are needed to confirm this finding, and to determine the effect of IVH interventions such as shunt or intraventricular thrombolysis.
Abstract T P271: Telestroke Alaska - Evidence Based Care Across the Great Frontier
Authors: Artuso Christie E
Published: July 2021

A primary objective in healthcare reform involves the delivery of evidence-based care and improved access to appropriate services for communities throughout the country. Over the past several years, telemedicine has become a sustainable model for delivery of healthcare services to support the care in geographically underserved areas. The use of telemedicine to deliver evidence-based care to patients with an acute focal neurologic deficit has resulted in consistent outcomes when evaluated through formal research projects. Barriers exist to the development of a robust telemedicine network including provider engagement, cost, reimbursement, education, and community collaboration. A formal and well-coordinated program utilizing appropriate strategic planning and carefully designed tactics can result in successful implementation as well as improved outcomes and access to care for rural communities. This presentation will use Alaska’s story to illustrate the development of a robust telemedicine network from its inception through deployment and concurrent process and performance improvement. Highlights of the presentation include the unique perspectives inherent to Alaska, including transportation [dog sleds are an option!], the weather and geography that Alaska is known for as well as the common challenges that are experienced in every new program as it is developed in healthcare systems across the country. Through a journey of experiences encountered in Alaska, this presentation will highlight a progressive understanding of the technology required to meet the needs of communities served, evaluation strategies, community benefit, and alignment with the vision of healthcare reform and delivery, the relationship to performance metrics, community advocacy and healthcare cost containment as well as strategies to mitigate risk and barriers in the implementation of similar programs.
Abstract T P276: Calling Stroke Alert: Does It Make a Difference in the Chain of Survival?
Authors: Small Cristine W , Price Donald L , Ferguson Jeffrey D , Madubeze Lawrence I , Freeman Susan D
Published: July 2021

Purpose:
To determine whether the stroke alert process results in improved outcomes, as reflected in door to lytic times and other outcome measures.

Introduction:
The diagnosis and treatment of stroke is time-sensitive and should be inclusive of all seven D’s in the “chain of survival” - Detection, Dispatch, Delivery, Door, Data, Decision and Drug (Adams, Stroke, 2007). Early stroke activation is part of the “Delivery” which incorporates transport and management by Emergency Medical Services (EMS).

Clinical suspicion of stroke by EMS resulted in a process of early activation which was labeled “Stroke Alert.” This expedited the code stroke process upon arrival, preparing the hospital based stroke team to provide immediate triage and evaluation. The goal was to improve clinical efficiency and possibly clinical outcomes.

Methods:
• Implementation of a notification process from EMS to ED - Stroke Alert

• Incorporated Stroke Alert to include Stroke Response Team (SRT) nurses January 22, 2011

• Retrospective review of internal stroke database (January 22, 2011 to July 2013) for comparative analysis of Stroke Alerts called versus those where no stroke alert was called

• Evaluate clinical outcomes directly related to Stroke Alert process

Results:
From January 22, 2011 to July 2013:

Stroke Alert Called:

• 37 t-PA patients and 14 of those, 37.8%, met the 60 minute benchmark

• Average Door to Lytic time - 65 minutes Stroke Alert NOT Called:

• 35 t-PA patients and 10 of those, 28.6% met the 60 minute benchmark

• Average Door to Lytic time - 79 minutes

Conclusions:
The ability for a SRT to meet the golden hour of stroke benchmark occurs more frequently when a Stroke Alert is called to the SRT nurse. Future plans include review of stroke severity scores, length of stay (LOS), and discharge disposition, to determine the impact a Stroke Alert may have on clinical outcomes.
Abstract T P28: Brain MRI FLAIR Signal Intensity Ratio Is Correlated With Matrix Metalloproteinase-9 Level In Acute Ischemic Stroke
Authors: Jha Ruchira M , Battey Thomas W , Pham Ly , Irvine Hannah , Furie Karen , Sheth Kevin , Kimberly William Taylor
Published: July 2021

Introduction:
Increased Matrix Metalloproteinase-9 (MMP9) level is associated with symptomatic hemorrhagic transformation (HT) after stroke. Higher risk of HT has also been reported in patients with early FLAIR hyperintensity on brain MRI.

Hypothesis:
We assessed whether FLAIR hyperintensity is associated with MMP9 levels.

Methods:
We retrospectively analyzed a cohort of acute stroke subjects who had acute brain MRI images and blood samples within the first 12 hours after onset of stroke. FLAIR hyperintensity was quantitatively assessed using FLAIR signal intensity ratio between the stroke lesion and corresponding normal contralateral hemispheres. For each subject, the FLAIR ratio was generated from the average of 6 regions of interest: 2 white matter and 2 gray matter regions each on 2 separate slices. MMP9 was measured using standard ELISA technique. Univariate and multivariate analyses were used to evaluate the relationship between FR and MMP9 and clinical covariates.

Results:
180 subjects had brain MRI and MMP9 available for analysis. MRI occurred within 6 ±3 hours and blood samples were drawn within 7 ± 4 hours from last seen well time. The mean MMP9 level was 238 ± 242 ng/mL and the mean FLAIR ratio was 1.40± 0.23. In univariate analysis, FLAIR ratio was associated with time to MRI (r= 0.18, p=0.01) and MMP9 (r=0.29, p<0.001). In multivariate analysis both FLAIR ratio (p<0.001) and time to MRI (p=0.003) remained associated with MMP9.

Conclusions:
There is a significant association between FLAIR ratio and MMP9 in acute stroke subjects. This raises the possibility that FLAIR hyperintensity reflects blood brain barrier changes during ischemia. Future studies to validate the prognostic value of FLAIR ratio in predicting symptomatic hemorrhagic transformation are warranted.
Abstract T P288: Improvement of Door to Groin Time for Endovascular Therapy in Acute Ischemic Stroke Using Quality Improvement Methods
Authors: Simpson Jennifer R , Graves Alexandra , Burrus Annie N , Case David E , Denton Christina J , Gebhard Laurel , Grant Matthew D , Smith Doreen A , Gupta Rajan K
Published: July 2021

Objective:
Time has been identified as a key variable to the success endovascular treatment of acute ischemic stroke. This project was designed to reduce the time from patient arrival to groin puncture for these treatments at a single academic hospital.

Methods:
Using Plan-Do-Study-Act (PDSA) quality improvement methodology, a multidisciplinary team was created to identify ways to reduce time from patient presentation to groin puncture. A comparison of pre-intervention and post-intervention times was performed. Pre-intervention patients were retrospectively identified using existing databases and post-intervention patients were prospectively identified. Process maps were created to identify areas of delay. Debriefs helped to indentify future process improvements. Four PDSA cycles have been completed. Stroke neurologists instituted an early notification of IR physicians and a unified imaging protocol. Other interventions included a group paging system, standardized order sets, education within each discipline, improved communication, standardized stroke tray set-up, and streamlining preparation of the patients prior to transportation from the ED.

Results:
The median time from presentation to groin puncture was reduced from 126 minutes to 92 minutes. MRI imaging was associated with a long pre-intervention time to groin puncture, with a median of 182 minutes that was reduced to 99 minutes. Procedures outside of normal business hours were associated with long time to groin puncture, with a median time of 149 minutes that was reduced to 125 minutes.

Conclusions:
A reduction of time from presentation to groin puncture is possible using PDSA cycles. This QI project decreased time to groin puncture by 26%, showing that a systematic evaluation of institutional-specific workflow can improve the process preceding a time-sensitive procedure.
Abstract T P329: Preadmission Use of Selective Serotonin Reuptake Inhibitors (SSRIs) in Acute Ischemic Stroke
Authors: Cutting Shawna , Smit Laurel , Jhu Renee , Ouyang Bichun , Prabhakaran Shyam
Published: July 2021

Objective:
To determine if patients admitted with ischemic stroke who were taking selective serotonin reuptake inhibitors (SSRI) at baseline have reduced motor impairment compared to patients not taking an SSRI.

Introduction:
SSRI use may help patients with motor recovery following ischemic stroke. It is not known whether use of this class of medications prior to stroke leads to decreased stroke severity or motor impairment on admission and improved discharge outcome.

Methods:
We retrospectively identified all patients admitted to our institution between 2009 and 2012 with first-ever acute ischemic stroke who were taking an SSRI prior to admission (cases). We collected data on patient demographics, clinical stroke severity as measured by the National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) score, and disposition at discharge. Controls with acute ischemic stroke who were not taking SSRIs prior to admission were matched 2:1 by age and gender to cases.

Results:
Eighty cases (mean age 65 +/- 14 years) were identified, of whom 56.2% were female and 63.7% were Caucasian. Median admission NIHSS was 5 (IQR 2-10), and median length of stay (LOS) was 4 days (IQR 3-7). Compared to controls, cases were more likely to have a pre-stroke diagnosis of depression (43.8% vs 7.5%, p=<0.001) or anxiety (13.8% vs 2.5%, p=0.001). Identification of a cardioembolic etiology was more common in cases (41.2% vs 26.6%, p=0.019). Median total NIHSS scores and NIHSS motor component scores on admission (total 5 vs 4, p=0.69; motor 2 vs 1, p=1.0) or at discharge (total 3.5 vs 2, p=0.67; motor 1 vs 0, p=0.76) were not different between cases and controls. Median LOS was similar for controls (5 days, p=0.65). Discharge to home or acute rehab was similar between groups (p=0.85).

Conclusions:
SSRI use prior to ischemic stroke does not confer a protective effect in reducing initial stroke severity, reducing degree of motor impairment, or improving discharge disposition. Further studies are needed to determine whether there are long-term benefits or other effects.
Abstract T P334: Clopidogrel and Aspirin versus Aspirin Alone for Prevention of Recurrent Ischemic Lesion in Acute Atherothrombotic Stroke: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Lee Seung-Hoon , Kim Hahn-Young , Bae Hee-Joon , Yu Kyung-Ho , Kim Gyeong-Moon , Kim Dong Eog , Cho Yong-Jin , Hong Keun-Sik , Kwon Sun U. , Rha Joung-Ho , Park Jong-Moo , Lee Soo-Joo , Lee Kyung Bok , Lee Yong-Seok , Cho Ki-Hyun , Cha Jae-Kwan , Kim Eung Gyu , Park Kwang-Yeol , Chang Dae Il , Choi Jay Chol , Cho Kyung-Hee , Kang Dong-Wha , Sohn Chul-Ho , Lee Jun , Yoon Byung-Woo
Published: July 2021

Background:
Combination treatment with clopidogrel and aspirin is not currently recommended for secondary prevention of stroke, but its superior effect to aspirin alone has been controversial according to stroke subtype and stage. We sought to compare the effect of aspirin and clopidogrel to aspirin alone for recurrent ischemic lesion in acute stage of atherothrombotic stroke.

Methods:
Combination of clopidogrel and aspirin for prevention of recurrence in acute atherothrombotic stroke study (COMPRESS) was a prospective, randomized, double-blind, placebo-controlled, multicenter trial. We enrolled 358 patients with acute atherothrombotic stroke within 48 hours after symptom onset, and randomly assigned them to receive clopidogrel (75 mg per day) plus aspirin (100 mg per day) or aspirin alone (100 mg per day) for 30 days. The primary endpoint was proportion of patients with a newly developed ischemic lesion within 30 days, as confirmed with brain MRI. Secondary endpoints were modified Rankin Scale scores at 30 days, occurrence of the composite endpoint of non-fatal stroke, myocardial infarction and cardiovascular death, and incidence of all types of stroke. The clinicaltrials.gov registration number for this trial was NCT00814268.

Results:
Among 358 patients enrolled, 349 patients who received at least one dose of study medication after randomization were included in the efficacy analysis population (clopidogrel plus aspirin, n=174; aspirin alone, n=175).Recurrent ischemic lesions were observed in 61 patients in the combination group (36.5%) and 60 patients in the aspirin alone group (35.9%; p=0.91). The significant difference was not found between the groups in the secondary endpoints. In the safety analysis, any bleeding incidence was non-significantly higher in the combination group (n=29 vs. n=19; p=0.10), and episodes of life-threatening hemorrhage and major hemorrhage were very low in both groups.

Conclusion:
Combination treatment of clopidogrel and aspirin is not superior to aspirin alone for prevention of recurrent ischemic lesion in acute atherothrombotic stroke patients.

Acknowledgement:
This study was co-sponsored by Sanofi-Aventis Korea and BMS Korea.
Abstract T P341: Impact Of Cytochrome P450 2C19 Polymorphism On High On-treatment Platelet Reactivity In Stroke Patients Treated With Clopidogrel
Authors: Tanaka Tomotaka , Miyata Shigeki , Yamamoto Haruko , Miyata Toshiyuki , Nagatsuka Kazuyuki ,   Cognac study investigators
Published: July 2021

BACKGROUND:
Clopidogrel is one of the most commonly used anti-platelet drugs. Recent reports suggested the association of allelic variants of the genes modulating metabolic activation (CYP2C19 and paraoxonase-1) and bioavailability (ABCB1) of clopidogrel with high on-treatment platelet reactivity (HTPR), possibly resulting in the recurrence of thrombotic events. However, these studies mostly examined patients with coronary heart disease and the impact of these polymorphisms in stroke patients is largely unknown.

METHODS:
We conducted a multicenter, prospective cohort study of 518 Japanese patients from 14 hospitals who were administrated clopidogrel. Residual platelet reactivity was determined by a change in light transmission induced by platelet aggregation in platelet-rich plasma after adding ADP. The vasodilator-stimulated phosphoprotein (VASP) index was also measured using flow cytometry. We investigated the association of polymorphisms of aforementioned enzymes with HTPR.

RESULTS:
In terms of CYP2C19 loss-of-function polymorphisms (*2 and *3), the prevalence of intermediate (IM: *1*2 or *1*3) or poor (PM: *2*2, *2*3, or *3*3) metabolizer was much higher (IM: 47% or PM: 15%) in Japanese than in Caucasian populations. Residual platelet reactivity was significantly higher in PM and IM groups than that in the wild-type extensive metabolizer (EM: *1*1) group assessed by 5 μM ADP-induced platelet aggregation (PM: 69.4% ± 17.1%, IM: 59.7% ± 16.2%, EM: 51.5% ± 17.5%, p < 0.0001) and VASP index (PM: 66.6% ± 14.1%, IM: 52.4% ± 16.0%, EM: 42.9% ± 15.0%, p < 0.0001). Furthermore, HTPR determined by both assays was associated with the ABCB1 polymorphism (rs1045642) but not with the paraoxonase-1 Q192R mutation.

CONCLUSIONS:
Our results indicate that both CYP2C19 and ABCB1 polymorphisms significantly contribute to HTPR in stroke patients treated with clopidogrel. At present, we are monitoring these patients for a two-year period to determine whether these genetic variants and HTPR affect the recurrence of thrombotic events.
Abstract T P363: Blood-Brain Barrier Damage in Vascular Risk Factor Associated White Matter Disease
Authors: Leigh Richard , Barker Peter B , Hillis Argye E
Published: July 2021

Background:
Vascular risk factor associated white matter disease (WMD), or leukoaraiosis, has been shown to demonstrate blood brain barrier damage (BBB) in patients with vascular dementia even when not detectable with standard clinical T1 post-contrast imaging.

Purpose:
We sought to study the prevalence of white matter BBB damage in a population of patients admitted to an inpatient stroke service.

Methods:
MRI scans of patients admitted for TIA or stroke were reviewed for evidence of confluent WMD in the centrum semiovale (CSO). To be included in the study patients must also have undergone a successful DSC image acquisition, also known as perfusion weighted image (PWI). The source images of the PWI were analyzed to generate blood-brain permeability images (BBPI) as described in a previous publication (Leigh et al, PLOS One 2012). The CSO in the first image above the lateral ventricles was used in each patient to generate BBPI measures. The pre-injection images of the PWI are T2* weighted and were therefore used to outline the area of confluent T2 signal change bilaterally. No acute strokes were present in any CSO analyzed as confirmed on DWI. The mean percent leakage (MPL) of contrast was calculated for each patient. A threshold of 2% of cerebral blood volume (CBV) was used to differentiate BBB damage from noise.

Results:
20 patients were included in the study, 8 were female, with a mean age of 65 years. The diagnosis was stroke in 15 patients and TIA in 5 patients. The location of the strokes were 5 pons, 3 basil ganglia, 3 periventricular, 1 thalamus, 1 cerebellar, 1 PCA, and 1 embolic shower. Of the 20 patients, 11 stroke patients and 3 TIA patients demonstrated BBB damage. The MPL ranged from 2.1% to 23.7% with an average value of 6.9% (of CBV). The MPL was even higher for the TIA group (12.2%) than for the for the stroke group (5.4%), although this difference failed to reach significance (p=0.056) .

Conclusions:
In patients admitted for stroke evaluation, BBB damage in confluent WMD is common. The relevance of this finding remains unclear. However there appears to be a trend towards increased BBB damage in patients who present with events that do not localize to an acute stroke; further research should be directed at establishing the clinical implications of BBB damage in this population.
Abstract T P4: Impact of Extended IV rt-PA Time Window and Immediate Endovascular Therapy on the Outcome in Patients with Major Artery Occlusion
Authors: Yamagami Hiroshi , Hayakawa Mikito , Koga Masatoshi , Sato Shoichiro , Ohara Tomoyuki , Kajimoto Katsufumi , Morita Ken-ichi , Satow Tetsu , Iihara Koji , Toyoda Kazunori , Nagatsuka Kazuyuki
Published: July 2021

Background and Purpose:
In Japan, indication of intravenous recombinant tissue plasminogen activator (IV rt-PA) therapy for acute ischemic stroke (AIS) has been extended to 4.5 hours after the onset from Aug, 2012. Additionally, we have modified our institutional strategy of endovascular treatment (EVT) to start immediately after IV rt-PA in patients with occlusions of internal carotid artery (ICA), proximal portion of middle cerebral artery (MCA), or basilar artery (BA) from Oct, 2012. This study aimed to clarify the impact of these changes on the outcome in patients with major artery occlusion.

Methods:
We investigated the AIS patients with ICA, MCA or BA occlusion admitted to our hospital within 24 hours after the onset. They were divided into two phases according to admission date: phase 1 (Oct, 2011 to Sept, 2012) or phase 2 (Oct, 2012 to Apr, 2013). Backgrounds, treatments, and outcomes were compared between two phases. Favorable outcomes were defined as modified Rankin Scale (mRS) ≦2 or equal to premorbid mRS, and poor outcome as mRS 5 or 6 at 90 days after the onset.

Results:
Among 248 patients (130 men, 76.1±12.4 years old, National Institute of Health Stroke Scale [NIHSS] score on admission: median 18 [IQR 11-24]), 152 patients were admitted in phase 1 and 96 in phase 2. Age, sex, onset to admission time, stroke subtype, and sites of occluded arteries were similar in two phases, while NIHSS score on admission was higher in phase 1 than 2 (median 19 vs 17, P=0.046). Compared to phase 1, IV rt-PA (36.8 vs 44.8%), EVT (12.5 vs 26.0%), and either reperfusion therapy (42.8 vs 54.2%) were more frequently performed, and door to IV rt-PA time (71 vs 61min.) and door to EVT time (148 vs 127min.) were shorter in phase 2. The rate of favorable outcome significantly increased (27.0 vs 40.6%, P=0.027) and that of poor outcome decreased (44.1 vs 30.2%, P=0.033) in phase 2. With multivariate analysis in total period, reperfusion therapy was associated to favorable outcomes (OR 2.24, 95% CI 1.05-4.80) and inversely associated with poor outcome (OR 0.29, 95%CI 0.13-0.64).

Conclusions:
Increased frequency of reperfusion therapy by extended IV rt-PA time window and rapid EVT may contribute to the improvement of outcome in AIS patients with major artery occlusion.
Abstract T P68: Delayed Progesterone Treatment Improves Long-Term Recovery of Function Following Permanent Stroke in Older Rats
Authors: Wali Bushra , Ishrat Tauheed , Won Soonmi , Sayeed Iqbal , Stein Donald
Published: July 2021

BACKGROUND:
Less is known about the long-term sustained effects of PROG on recovery of function following stroke. Two objectives were evaluated, First, whether functional deficits caused by pMCAO persist and if repeated testing in itself reduce the extent of injury over long periods (8 weeks). Second, determine PROG's effects on a panel of behavioral tests performed several weeks post-pMCAO

Methods:
Male Sprague-Dawley rats (12 months old) underwent pMCAO by electrocoagulation or sham surgery. For the first study, repeated long term group with pMCAO began a battery of tests at repeated intervals (during the 3rd, 6th, and 8th weeks post-pMCAO), while long term with pMCAO group testing began during the 8
th
week post-pMCAO. For the second study, beginning 3 h post-occlusion, rats were given IP injections of 8 mg/kg of PROG or vehicle, followed by SC injections at 8 h and then every 24 h for 9 days with tapering of final 2 treatments. All animals received: motor, sensory and cognitive tests; grip strength, rotarod, sensory neglect tests and spatial navigation learning and memory test; and computerized analysis of gait impairment.

Results:
Functional deficits caused by pMCAO showed modest improvement over time but were still persistent in older rats. Repeated testing (3 times over 8 weeks) did not reduce the effects of injury. Despite modest recovery in vehicle treated rats at eight weeks post-pMCAO, PROG treatment given 3 h after stroke and compared with vehicle group, showed improvement in grip strength by 59.28%, rotarod stability by 46.36 %, reduced sensory neglect by 28.69% and memory deficits by 38.56%. Automated gait assessment showed that PROG treatments significantly improved motor deficits in the affected limb on parameters like stride length, strand, paw print, and swing cycle.

Conclusions:
1. The above tested behavioral assays over long-term assessment period, can be used for evaluating therapeutic agents in models of ischemic stroke in older rats. 2
.
PROG was found to have sustained effect up to 8 weeks post stroke. PROG shows pre-clinical promise and should be examined for safety and efficacy in a clinical trial for ischemic stroke.
Abstract T P75: Temporal Profiles of Plasminogen Activator Inhibitor-1 Concentration and Activity Changes in Circulation after Focal Stroke and Tissue Type Plasminogen Activator Administration in Rats
Authors: Liu Qi , Fan Xiang , Brogren Helen , Ning Ming-Ming , Lo Eng H , Yu Zhanyang , Wang Xiaoying
Published: July 2021

Aims:
Plasminogen activator inhibitor-1 (PAI-1) is the main and potent endogenous tissue-type plasminogen activator (tPA) inhibitor, but an important question on whether PAI-1 in blood stream responds and interferes with the exogenously administered tPA remains unexplored. We for the first time investigated temporal profiles of PAI-1 concentration and activity in circulation after stroke and tPA administration in rats.

Methods:
Permanent MCAO focal stroke of rats were treated with saline or 10mg/kg tPA at 3 hours after stroke (n=10 per group). Plasma (platelet free) PAI-1 antigen and activity levels were measured by ELISA at before stroke, 3, 4.5 (1.5 hours after saline or tPA treatments) and 24 hours after stroke. Since vascular endothelial cells and platelets are two major cellular sources for PAI-1 in circulation, we measured releases of PAI-1 from cultured endothelial cells and isolated platelets after direct tPA (4 μg/ml) exposures for 60 min in vitro by ELISA (n=4 per group).

Results:
At 3 hours after stroke, both plasma PAI-1 antigen and activity were significantly increased (3.09±0.67, and 3.42±0.57 fold of before stroke baseline, respectively, all data are expressed as mean±SE). At 4.5 hours after stroke, intravenous tPA administration significantly further elevated PAI-1 antigen levels (5.26±1.24), while as expected that tPA neutralized most elevated PAI-1 activity (0.33±0.05). At 24 hours after stroke, PAI-1 antigen levels returned to the before baseline level, however, there was a significantly higher PAI-1 activity (2.51±0.53) in tPA treated rats. In vitro tPA exposures significantly increased PAI-1 releases into culture medium in cultured endothelial cells (1.65±0.08) and platelets (2.02±0.17).

Conclution:
Our experimental results suggest that tPA administration may further elevate stroke-increased blood PAI-1 concentration, but also increase PAI-1 activity at late 24 hours after stroke. The increased PAI-1 releases after tPA exposures in vitro suggest tPA may directly stimulate PAI-1 secretions from vascular walls and circulation platelets, which partially contributes to the PAI-1 elevation observed in focal stroke rats. The underlying regulation mechanisms and pathological consequence need further investigation.
Abstract T P77: Synergistic Effects of Platelet Lysate and Granulocyte-Colony Stimulating Factor on Safe and Rapid Expansion of Human Bone Marrow Stromal Cells for Ischemic Stroke
Authors: Yamauchi Tomohiro , Kuroda Satoshi , Saito Hisayasu , Shichinohe Hideo , Houkin Kiyohiro
Published: July 2021

Purpose:
Human bone marrow stromal cells (hBMSCs) are the most promising donor cells of cell therapy for ischemic stroke. For clinical application, it is essential to establish the protocol to expand the hBMSCs in the animal protein-free medium within significant time limit. This study was aimed to evaluate the effects of human-derived platelet lysate (PL) and granulocyte-colony stimulating factor (G-CSF) on their growth kinetics, neural differentiation, and therapeutic ability in ischemic stroke.

Methods:
The hBMSC were cultured in three types of culture media, including FCS-containing medium (hBMSC-FCS), PL-containing medium (hBMSC-PL), and PL and G-CSF-containing medium (hBMSC-PL/G-CSF). Cell growth kinetics was compared among three groups. The rats were subjected to permanent middle cerebral artery occlusion. The hBMSCs-PL, hBMSCs-PL/G-CSF or vehicle was stereotactically transplanted into the ipsilateral striatum at 7 days after the insult. Motor function was serially evaluated throughout the experiments. The distribution and fate of engrafted cells were examined, using fluorescence immunohistochemistry.

Results:
The culture with PL and G-CSF significantly shortened the doubling time of hBMSCs. Transplantation of the hBMSCs promoted functional recovery compared with vehicle. The therapeutic effects did not differ between hBMSCs-PL and hBMSCs-PL/G-CSF. Engrafted hBMSCs aggressively migrated toward the infarct rim and some of them acquired the phenotypes of neurons and astrocytes.

Conclusion:
These findings strongly suggest that the animal protein-free, pharmacologically modulated protocol enables a safe and quick expansion of hBMSCs for patients with ischemic stroke in clinical situation.
Abstract T P84: Beneficial Stroke Outcomes Following Epicatechin Consumption in Young and Older Mice
Authors: Leonardo Christopher , Dore Sylvain
Published: July 2021

Background:
The consumption of flavanol containing foods, including (-)-epicatechin, has been linked to lower incidence of cardiovascular disease and stroke. We have previously demonstrated that epicatechin prophylaxis reduces stroke-induced anatomical and functional deficits in young, healthy mice; yet clinical stroke is primarily a disease of the elderly. Since neuroinflammation and vascular dysfunction are associated with aging, we aimed to test whether epicatechin is also protective in aging mice subjected to experimental stroke, and if so, whether this results from reduced glial cell activation and blood brain barrier permeability.

Methods:
Twelve-month-old wildtype and C57BL/6 Nrf2 knockout mice were administered 15mg/kg epicatechin, the minimum effective dose in young, healthy mice, prior to permanent distal middle cerebral artery occlusion. Mice were evaluated for functional recovery at one day post-stroke using the Adhesive Removal Test. Infarct volume, gliosis, and blood brain barrier permeability estimates were conducted seven days following stroke.

Additionally, we compared anastomosis in wildtype and Nrf2 knockout mice and assessed hemorrhage frequency in studies using four- and 12-month-old mice.

Results:
Consistent with previous results in young mice, 12-month-old wildtype mice pretreated with epicatechin showed significant reductions in infarct volume and latency to remove adhesive tape relative to vehicle-treated controls, while Nrf2 knockout mice were not protected by epicatechin. Interestingly, epicatechin did not reduce Iba1 immunoreactivity or mouse IgG extravasation at seven days post-stroke. Similarly, there were no significant differences in anastomosis or spontaneous hemorrhage between wildtype and Nrf2 knockouts, indicating that cerebral vascular physiology is similar and gross vascular integrity was unaffected by treatment.

Conclusion:
Thus, although epicatechin prophylaxis reduces infarct volume and functional deficits, it does not exert sustained effects on gliosis or cerebrovascular integrity in aging mice.
Abstract T P90: Characterization of Inflammatory Cells after EDAS Surgery in Patients with Intracranial Arterial Stenosis
Authors: Gonzalez Nestor R , Iruela-Arispe Luisa
Published: July 2021

Introduction:
Indirect revascularization via encephaloduroarteriosynangiosis (EDAS) establishes collateral flow through new vessels formed from external carotid branches in patients with moyamoya disease and intracranial arterial stenosis (IAS) of non-moyamoya origin. A better understanding of the process of neovascularization is key to improve the potential therapeutic effects of these techniques. To gain a more in-depth understanding on the mechanisms behind the pro-angiogenic effects, we performed detailed evaluation of cellular changes in circulating monocytes.

Methods and Results:
Dynamics in inflammatory cell were assessed by cell surface marker analysis by flow cytometry of blood from patients at 24, 48 and 72 hours and compared to baseline control (pre-operative) levels from the same patient. While increase in CD45+ cells was noted at 24hrs in all patients, a particularly impressive elevation in the percentage of CD11b/Gr1 positive cells was found in patients at 48 and 72hrs post-surgery. Although CD11b suggested a monocytic population, these cells were F480 low/negative indicating a shift in the differentiation of monocytes or exit of a different population of inflammatory cells from the bone marrow.

Conclusions:
Our findings are in accordance with recent publications suggesting a pro-angiogenic role of macrophages during vascular expansion and repair. The findings are consistent with the concept that CD11b/Gr1 cells might constitute an important subset of monocyte/macrophages poised to mediate vascular repair upon stroke and could represent a clinically valuable tool.
Abstract T P97: A Swine Model of Restenosis after Intracranial Stent Deployment
Authors: Liu Zhong , Wang Jin-Shan , Liu Dong-Hong , Zhang Xiang-Song , Chen De-Ji , Liu Ying , Liu Yan-Qiu , Shi Xin-Chong , Li Ming-Chang , Feng Lei , Shi Zhong-Song
Published: July 2021

Purpose:
Although various types of stents have been used to treat symptomatic intracranial stenosis, how stents interact with atherosclerotic plaques has not been evaluated. In this study, we demonstrate the utility of a swine carotid atherosclerotic model for the preclinical evaluation of intracranial stenting therapies.

Methods:
Advanced atherosclerotic plaques were induced in 28 carotid arteries of 14 Chinese miniswines using partial ligation and high cholesterol diet to create >70% stenosis. The plaques were characterized with three-dimensional rotational angiography, Doppler ultrasonography, MR scan and 18F-FDG PET/CT scans at three months and correlated with histopathological examination in 20 carotid arteries. Five Wingspan stents and one Paclitaxel-eluting balloon-mounted coronary stent were implanted into six diseased vessels. Two contralateral carotid arteries were used as controls. Dual-antiplatelet regimen with clopidogrel and aspirin was administrated 1 day prior to stenting and continued for 1 month. Stent and plaque interaction was evaluated with angiography, MR scan and 18F-FDG PET/CT scans at one month after stenting.

Results:
The diameter of proximal and distal segments of carotid arteries were 3.6±0.1 mm and 3.8±0.1 mm at post-ligation, and 3.6±0.1 mm and 3.7±0.1 mm at 3 months, respectively, similar to that of middle cerebral arteries in human (2.7-4.9 mm, average 3.7mm). Doppler waveforms showed features of low resistant vessels. Plaque rupture and distal embolism were observed, mimicking the mechanisms of stroke in human intracranial atherosclerosis. All stents were patent at one month but 25% restenosis was observed. Wingspan stents expanded beyond the arterial lumen whereas the coronary stent stayed in the intima.

Conclusion:
This swine model is suitable for the testing of devices for the endovascular treatment of intracranial atherosclerosis. It can be a useful tool for the study of mechanisms of in-stent restenosis.
Abstract W MP100: Hospital SAH Volume Associated With Better Outcomes
Authors: Pandey Aditya S , Chaudhary Neeraj , Gemmete Joseph J , Thompson Byron G , Burke James
Published: July 2021

Objective:
The net impact of hospital care on outcomes in subarachnoid hemorrhage (SAH) has not been well established. We hypothesized that increased experience and technical expertise at high volume hospitals would lead to better outcomes.

Methods:
We performed a serial cross-sectional retrospective study using the Nationwide Inpatient Sample from 2002-2010. All adult (>18 years) discharges with a primary diagnosis of SAH (ICD-9-CM 435) from 2002-2010 were included and records with trauma or AVM were excluded. Survey-weighted descriptive statistics were used to estimate temporal trends. Multi-level logistic regression was used to estimate volume-outcome associations for two outcomes: inpatient mortality and discharge home. Models were adjusted for demographics, year, transfer status, insurance status, all individual Charlson comorbidities, intubation, and APR-DRG mortality. Analyses were repeated by excluding records where aggressive care was not pursued _ no intubation, no procedures and in-hospital death within 48 hours.

Results:
A total of 66,818 discharges were included in the weighted sample, including 19, 356 who received clipping or coiling. Inpatient mortality declined from 32.2% (30.1%- 33.9%) to 22.2% (20.8%-23.6%) from 2002 to 2010 while discharges to home increased from 28.5% (27.0-30.03%) to 40.8% (39.1%-42.4%). Hospitals in the highest volume quintile (greater than 63 discharges per year) had an unadjusted inpatient mortality of 22.7% (95% CI 22.0%-23.2%) compared to 41.5% (39.0%-43.7%) in quintile 3 (11-21 discharges per year) compared to 51.9% (47.0 -55.7%) in quintile 1 (less than 6 discharges per year). Similar trends were observed when excluding cases where aggressive care was not pursued. The proportion of patients discharged home also increased with hospital volume: 39.3 %( 38.0-39.9%) in quintile 5 vs. 23.2% (21.0%-25.1%) in quintile 3 vs. 16.7% (13.0%-19.7%) in quintile 1.

Conclusion:
Inpatient SAH mortality has decreased over time while the likelihood of discharge home has increased. High volume hospitals have more favorable outcomes than low volume hospitals and the magnitude of this effect is substantial. SAH volume should be accounted for in developing SAH systems of care.
Abstract W MP105: Long Term Stroke Outcome and Caregiving Among Mexican Americans (MA) and Non-Hispanic Whites (NHW): The Population-Based Brain Attack Surveillance in Corpus Christi (BASIC) Study
Authors: Sanchez Brisa N , Lisabeth Lynda , Zahuranec Darin , Cox Melinda A , Garcia Nelda , Morgenstern Lewis
Published: July 2021

Background:
Long term stroke outcomes in MA are understudied, and the role of informal caregiving and caregiver strain in this population is unknown. We report a pilot study of long-term outcomes in BASIC.

Methods:
Patients previously interviewed at 90 days post-stroke were invited to participate in a telephone survey related to their 6 or 12 month post-stroke activities of daily living (ADLs) during March-May 2013. ADL score (average of 7 items, range 1-4) was analyzed by self-reported ethnicity using repeated measures models. In a separate sample interviewed at 90 days, patients were asked about willingness to participate in longer term follow-up and a subset of caregivers responded to the caregiver strain index (CSI, range 1-13, higher is worse).

Results:
Among patients alive at the time of interview, 87% of 39 MA and 74% of 19 NHW participated in the 6 month interview, and 84% of 32 MA and 88% of 8 NHW participated in the 12 month interview. No patients refused at either time point; the remainder could not be contacted. The figure shows trajectories of ADL score by ethnicity, and worsening scores among MA over time. Interest in longer-term follow-up was high (96% of 25 NHWs and 97% of 38 MAs). Caregivers of MA stroke survivors were most often children (41%) followed by spouses (36%), but were spouses (43%) followed by children (29%) for NHWs. Of 29 caregivers interviewed, 54% of MA and 57% of NHW reported being strained (CSI≥7). Caregiver strain was associated with 90-day ADL score: prevalence ratio = 1.34, 95%CI (1.01, 1.76) for 1 unit increase in ADL score.

Conclusions:
Our data demonstrate the feasibility of recruiting MA stroke survivors for long-term outcome assessments and suggests that MAs have worse functional outcome and greater functional declines than NHWs. The informal caregiver burden is related to functional outcome and is high in both ethnic groups.
Abstract W MP20: PerfAngio: A Software Solution for Quantitative Perfusion Angiography
Authors: Scalzo Fabien , Ahluwalia Amrit S , Huang Zibing , Ren Gary , Liebeskind David S
Published: July 2021

Background:
Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. The video densitometric theory has established in the early 1980’s the relationship between the intensity of DSA images and blood flow. This theoretical foundation enables the computation of parametric maps summarizing blood volume, flow, and delay by tracking the injected contrast agent across the vasculature. Although perfusion imaging is widely used with MR and CT, it has yet to be translated into accessible software for DSA.

Methods:
We introduce Perfusion Angiography (PerfAngio) software to calculate multi-parametric perfusion maps, including: CBV, CBF, MTT, TTP, and Tmax. These are produced by deconvolution of the time-density curve with the arterial input function and displayed as high-definition color-coded images; an innovative way to visualize perfusion. The application, PerfAngio, will be freely available for the iPad tablet. A user-friendly web interface (http://www.perfangio.com) will allow clinicians to upload their own datasets and visualize/download the quantitative results.

Results:
In addition to providing visualization of unique features, never seen before on DSA, PerfAngio has been successfully used to retrospectively analyze multi-center datasets. The software demonstrated feasibility and performance to evaluate angiographic outcome in TREVO2. It was also a useful tool to compare the hemodynamic impact of devices during thrombectomy in TREVO2 and stenting in SAMMPRIS. Yet, numerous questions remain to be studied with PerfAngio, including identification of futile recanalizaton, hemorrhagic transformation, correlation with MRI and CT and automatic quantification of collateral flow.

Conclusions:
This revolutionary imaging software can provide insights into Stroke from standard DSA. It is particularly promising for retrospective studies and during clot-retrieval interventions as it offers an objective, continuous measure to characterize angiographic observations.
Abstract W MP21: Contrast Staining on Ct After Endovascular Treatment for Acute Ischemic Stroke: Association With Worse Outcomes
Authors: Cheng-Ching Esteban , Hussain Muhammad S , Toth Gabor , Obuchowski Nancy , Man Shumei , Wisco Dolora , Uchino Ken , Hui Ferdinand
Published: July 2021

Introduction:
Parenchymal contrast staining may appear on computerized tomography after intra-arterial therapy for acute ischemic stroke. This finding may not be associated with hemorrhagic transformation and has been reported to be transient. However, the incidence, associations and clinical consequences have not been well described.

Methods:
We reviewed a prospectively collected database of acute ischemic stroke patients admitted between January of 2012 and April of 2013. We included patients with acute ischemic stroke and large vessel occlusion who underwent endovascular therapy. Demographic, clinical and imaging characteristics were assessed. Post-procedure brain CTs were reviewed for contrast staining and ASPECTS score. Discharge and 30-day follow up data were compared using Wilcoxon two-sample tests and chi square tests.

Results:
59 patients (34 (57.6%) female, mean age: 66.7 years;) were included in the analysis. Twenty two patients (37.3%) had contrast staining on post-procedure brain CT scan. Of this group, the initial median NIHSS was 16.5 and initial median ASPECTS score was 7 (compared to initial median NIHSS of 15 and median ASPECTS of 9 in those without contrast staining) (p=0.297 and 0.166, respectively). Recanalization rates were similar for both groups (82% vs. 83%, p=0.882). Upon discharge, the group of patients with post-procedure CT with contrast staining had significantly higher NIHSS (median of 15) and lower CT ASPECTS score (median of 6), (compared to NIHSS of 7 and CT ASPECTS of 8 in those without contrast staining) (p=0.025 and 0.017). Patients who had contrast staining tended to be more likely to have a hemorrhagic transformation of the ischemic infarct area (59.1% versus 36.1%, p=0.088) with rates of PH1 being 18.2% (versus 8.1%, p=0.407) and PH2 being 22.7% (versus 5.4%, p=0.090). The data also suggest a difference in the 30-day NIHSS (10 in the contrast staining group versus 4, p=0.092) and 30-day MRS (4 in the contrast staining group versus 3, p=0.107).

Conclusion:
The presence of contrast staining on CT obtained after intra-arterial therapy for acute ischemic stroke may be associated with worse imaging and clinical outcomes, including hemorrhagic transformation and worse neurologic deficits upon discharge and at 30 days.