bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP265: Interferon-inducible Protein 10 Increases following Stroke
Authors: Seifert Hilary A , Collier Lisa A , Benkovic Stanley A , Willing Alison E , Pennypacker Keith R
Published: July 2021

Objective:
The splenic response to injury furthers cellular degeneration as its removal is protective in ischemic injuries to several organ systems including the brain. Previously, we have shown that the proinflammatory cytokine interferon gamma (IFNg), which activates microglia/macrophages, is elevated in the spleen and the brain following permanent middle cerebral artery occlusion (MCAO). IFNg induces the production of interferon-inducible protein 10 (IP-10) which further propagates the inflammatory response. Therefore, we investigated the expression of IP-10 in the brain and spleen following ischemic stroke.

Hypothesis:
IFNg production in the brain and the spleen results in elevated levels of IP-10 in the same tissues post-MCAO.

Methods:
A time course was conducted to investigate splenic and brain protein levels of IP-10 in rats over time following MCAO and sham-MCAO (n≥3). In a second experiment, rats were administered an IFNg neutralizing antibody following MCAO with a survival time of 96 h: vehicle control (n=4), goat IgG 5μg (n=7), and IFNg antibody 5μg (n=7). Spleens and brains were collected for all groups.

Results:
IP-10 levels were significantly elevated in the brain at 72 and 96 h post-MCAO (p<0.01) compared to naïve brains. In the spleen IP-10 levels become significantly elevated at 24 h and remain elevated out to 96 h post-MCAO (p<0.0007) compared to naïve spleens. Administration of a neutralizing antibody directed against IFNg significantly decreased IP-10 levels in the brain (p<0.009) but did not affect IP-10 levels in the spleen.

Conclusion:
These results demonstrate that increased production of IFNg results in elevated levels of IP-10 in both the spleen and the brain following stroke. However, administration of a neutralizing antibody against IFNg decreased the amount of IP-10 in the brain. Levels of IFNg and IP-10 in the brain increase at the same time following stroke. Based on these data, IFNg propagates a proinflammatory T helper cell response to stroke through IP-10. Inhibition of this signaling could reduce neuroinflammation thereby improving stroke outcome.
Abstract WP280: Use of Strategies to Improve Door-to-Needle Times with Tissue Plasminogen Activator in Acute Ischemic Stroke by US Hospitals: Findings from the Target: Stroke Survey
Authors: Fonarow Gregg C , Smith Eric E , Zhao Xin , Peterson Eric D , Xian Ying , Olson DaiWai M , Hernandez Adrian F , Bhatt Deepak L , Saver Jeffrey L , Schwamm Lee H
Published: July 2021

Background:
The benefits of intravenous tissue-plasminogen activator (tPA) in acute ischemic stroke are time-dependent and several strategies have been reported to be associated with more rapid door-to-needle (DTN) times. However, the extent to which hospitals are utilizing these strategies has not been well studied.

Methods:
We surveyed 304 hospitals joining Target: Stroke regarding their baseline use of strategies to reduce door-to-needle times in the 1/2008-2/2010 timeframe (prior to the initiation of Target: Stroke). The survey was developed based on literature review and expert consensus for strategies identified as being associated with shorter DTN times and further refined after pilot testing. Categorical responses are reported as frequencies.

Results:
Hospitals participating in the survey were 50% academic, median 163 (IQR 106-247) ischemic stroke admissions per year, median 10 (IQR 6-17) tPA treated patients per year, and had median 79 minute (IQR 71-89) DTN times. By survey, 214 of 304 hospitals (70%) reported initiating or revising strategies to reduce DTN times in the prior 2 years. Reported use of the different strategies varied in frequency, with use of ischemic stroke critical pathways, CT scanner located in the Emergency Department, and tPA being stored in the Emergency Department being the strategies least frequently employed (Table). As part of Target: Stroke participation, 279 of 304 hospitals (91.5%) indicated they planned to have a dedicated team focused on reducing DTN times.

Conclusions:
While most US hospitals participating in this survey report use of the strategies to improve the timeliness of tPA administration for acute ischemic stroke, significant variation exists. Further research is needed to understand which of these strategies are most effective in improving acute ischemic stroke care.
Abstract WP292: Quantitative Susceptibility Mapping for Reliably Measuring Hematoma Volume in Magnetic Resonance Imaging
Authors: Wang Shuo , Lou Min , Liu Tian , chen xiaomei , Wang Yi
Published: July 2021

Introduction
T2* weighted gradient echo MRI has been increasingly recognized as a sensitive tool in detecting intracerebral hemorrhage. However, its blooming artifacts is highly dependent on imaging parameters including TE, field strength and voxel size, making it difficult to reliably estimate the hematoma volume, a key predictor of morbidity and mortality of hemorrhage. Recently, a novel quantitative susceptibility mapping (QSM) technology has been developed for processing gradient echo MRI data to map tissue susceptibility property without blooming artifacts and dependence on imaging parameters.

Hypothesis
We assessed the hypothesis that hematoma volume measurement on QSM is independent of imaging parameters, eliminating its TE dependence on gradient echo MRI.

Method
A retrospective image analysis of MRI was approved by our IRB with HIPPA compliance. We randomly selected 16 patients who underwent intracerebral hemorrhage MRI including a 3D multiecho T2*w sequence: 8-11 echoes with first echo TE/ echo spacing/ TR= 5/5/50 msec. Postprocessed images of gradient echo MRI included susceptibility weighted imaging (SWI), R2* (quantitative 1/T2* mapping), and QSM at various TEs. Hematoma volumes were measured from all these images.

Results
Linear regression of hematoma volume vs TE over all subjects showed substantial slopes for gradient echo magnitude (0.45±0.31 L/s), SWI (0.52±0.46) and R2* (0.39±0.30) but nearly zero slope for QSM (0.01±0.05). At TE=20 msec, hematoma volume on QSM was 0.80x that on gradient echo magnitude image (R2=0.99), and hematoma volume on CT is also 0.8x that on gradient echo magnitude image according to literature (Stroke 2008;39:2017-2020).

Conclusion
In conclusion, quantitative susceptibility mapping can provide reliable measurement of hematoma volume, independent echo time and similar to CT.
Abstract WP329: A Functional Recovery Analysis of Inpatient Rehabilitation for Mild Stroke Patients
Authors: Pageau Nicole , Lindsay Patrice , Bayley Mark
Published: July 2021

Background / Purpose:
Organized stroke care within the rehabilitation setting has improved functional outcomes and enable stroke patients to re-integrate within the communities. The Evidence Based Systematic Review for stroke recommends that mild stroke patients with a FIM
®
> 80 could receive therapy within the community. However, in Ontario, approximately 20% of mild stroke patients continue to be admitted to inpatient rehabilitation. The purpose of this study is to identify the differences between the mild stroke patients being admitted to inpatient rehabilitation and being discharged home directly from acute care and propose a triage system for the mild stroke population.

Methods:
A retrospective chart audit was conducted for acute stroke discharges from two regional stroke centres in Ontario. The cohort included patients with a most responsible diagnosis of stroke and a completed AlphaFIM
®
Instrument assessment. Stroke cases that had a Projected Full FIM
®
score derived from the AlphaFIM
®
Instrument with a score > 80, we’re stratified into two groups:discharged home and discharged to inpatient rehabilitation. Data was analyzed using a full and step wise regression model to determine which indicators impacted the discharge disposition.

Results:
There were 813 patients were eligible for inclusion. The mean age of participants was 72 years, and 54% were males. Overall, 33% of mild stroke patients were admitted to inpatient rehabilitation. The results of the analysis did not explain why so many mild stroke patients are admitted to inpatient rehabilitation. There was a trend toward mild stroke patients with aphasia, inattention and cognitive impairments being admitted to inpatient rehabilitation; however, this was not statistically significant. These two groups did not differ in rates of recurrent stroke or re-admission to hospital at follow-up.

Conclusion:
The results of this research indicates that milder stroke patients with a Projected Full FIM
®
> 80 may effectively be managed in the community if appropriate rehabilitation services are available. Further research is warranted to evaluate functional outcomes of stroke patients within the community rehabilitation setting in order to determine its efficiencies.
Abstract WP338: Development of a Veteran Specific Stroke Educational Guide
Authors: Stonecypher Karen , Willson Pamela
Published: July 2021

Background and Purpose:
Nearly 6,000 veterans are hospitalized annually for an ischemic stroke. The Veteran’s Health Administration (VHA) estimates care cost at $111 million for acute inpatient care, $75 million post-acute inpatient care, and $88 million for the first six months post stroke follow-up care. Presently, few national publications are uniquely designed for the veteran population. The primary focus of this initiative was to lead a multidisciplinary team of experts in the development of a veteran specific stroke risk prevention and reduction educational guide.

Methods:
A nurse lead multidisciplinary team of experts were assembled to develop a disease and population specific patient educational guide. The VHA educational guidelines, chronic disease self-management, and the Joint Commission Stroke educational core measures were used as the developmental framework. Mort Walker, creator of Beetle Bailey, provided illustrations throughout the guide for key concepts that were veteran specific and culturally-appropriate. The
Sergeant
Snorkel
character emulates an ideal role model for veterans on how to prevent and reduce stroke risks.

Results:
A 28 page guide was developed for electronic distribution to healthcare providers across the VHA system. The printed version was designed to be the pivotal organizing resource for veteran and caregiver education during the hospital stay. The incorporation of self-management skills makes this guide uniquely different from other educational manuals. Documentation of self management implementation includes goal setting, action planning, and problem solving. The didactic components addressed are medication management, dietary compliance, smoking cessation, weight loss, increasing physical activity, improving functional status, and self-management skills. Development facilitators will be discussed.

Conclusions:
A nurse led multidisciplinary team of experts was assembled to develop a disease and population specific patient education guide for military veterans who have experienced a stroke. Veteran specific artwork seems to lend credibility to the health information for this population. The guide’s unique self-management documentation aides ease of use.
Abstract WP375: Quality of Care and In-Hospital Outcomes by Race and Ethnicity among Patients Hospitalized with Intracerebral Hemorrhage: Findings from 123,623 Patients in the Get With The Guidelines-Stroke Program
Authors: Xian Ying , Holloway Robert , Smith Eric , Schwamm Lee , Reeves Mathew , Bhatt Deepak , Cox Margueritte , Olson DaiWai , Hernandez Adrian , Lytle Barbara , Fonarow Gregg , Peterson Eric
Published: July 2021

Background:
The rates of intracerebral hemorrhage (ICH) are disproportionally higher in minorities. While racial/ethnic differences in care persist in many areas of medicine, no study to date has examined whether ICH care processes or outcomes differ by patient race or ethnicity.

Methods:
We analyzed data from 123,623 ICH patients (83,216 white; 22,147 black; 10,519 Hispanic; and 7,741 Asian) hospitalized at 1,199 Get With The Guidelines-Stroke hospitals between 2003 and 2012. Multivariate logistic regression with generalized estimating equation was used to evaluate the association between race, stroke performance measures, and in-hospital outcomes.

Results:
Relative to white ICH patients, black, Hispanic, and Asian ICH patients were younger, more frequently had diabetes mellitus, hypertension, and more severe stroke (median National Institutes of Health Stroke Scale [NIHSS]:9, 10, 10, and 11, respectively, p<0.001). After adjusting for both patient- and hospital-level characteristics (Table), black ICH patients were more likely than whites to receive deep venous thrombosis prophylaxis, rehabilitation assessment, dysphagia screening, and stroke education, but less likely to receive smoking cessation counseling despite high prevalence of black current smokers. All minority groups had lower rates of in-hospital mortality (27.6%. 23.0%, 22.8%, and 25.3% for white, black, Hispanic, and Asian, respectively; p<0.001), but were more likely to experience a longer length of stay (median 5, 6, 6, and 6 days, respectively; p<0.001) than white patients. These differences remained consistent after further adjustment for NIHSS among NIHSS complete records (N=47,408).

Conclusion:
We found no clear pattern of racial or ethnic differences in the quality of care delivered to ICH patients. Black, Hispanic, and Asian ICH patients had lower risk-adjusted mortality compared with their white counterparts.
Abstract WP42: CT Perfusion in Acute Stroke: Substantial Value Beyond Penumbra
Authors: Meng Sarah W , Hewitt Michael , Liu Xiang
Published: July 2021

Purpose:
The role of CT Perfusion (CTP) in evaluation of acute stroke remains controversial, especially in determining ischemic penumbra and core infarct. Thus, our institution suspended CTP as part of the acute stroke imaging protocol, and now includes a non-contrast head CT (NCCT) and CT angiography (CTA) of the head and neck. We performed a retrospective review of cases using NCCT, CTA and CTP (CT-CTP) and cases using NCCT and CTA (CT-CTA protocol) at our institution from 2009 to 2011, to assess what, if any, substantial benefit CTP provides in the management of acute stroke.

Methods:
A total of 758 cases were reviewed, including 375 cases in the CT-CTP protocol and 383 cases in the CT-CTA protocol. Acute infarcts limited to the area covered by CTP were reviewed to compare the diagnostic sensitivity of the two protocols. Followup DWI or NCCT was used as the reference standard for final infarct size. Infarct volume was measured by freehand region of interest measurement. A subset group with final infarct volume > 30ml was also reviewed to explore the detection sensitivity of vascular thrombosis.

Results:
CTP deficits were reported in all 71 cases with a final infarct volume of 2.8 ml and above. Conversely, in the same category, 23 of 96 (24%) cases were reported as negative with CT-CTA protocol. Of the 10 cases with final infarct volume > 30ml and reported as negative in the CT- CTA protocol, 7of 10 had 2nd or 3rd order vascular thromboses, including 6 cases with infarct volume > 50ml. Only 2 of 45 thromboses were missed in the same category with CT-CTP protocol. Vascular thrombosis was missed in 1 of 10 cases with final infarct volume > 30ml in the CT-CTP protocol where NCCT was reported as negative but had positive CTP deficits.

Conclusions:
There is a substantially greater detection rate of 2nd and 3rd order vascular thrombosis when CTP is performed, including cases when NCCT is deemed negative. We speculate that a negative NCCT may provide false assurance, but that CTP deficits will guide attention to the area of interest, ultimately increasing detection of vascular occlusion and potentially influencing treatment options in the setting of acute stroke. Additionally, CTP significantly increases the diagnostic sensitivity of acute stroke compared to a combination of NCCT and CTA alone.
Abstract WP422: Vitamin D deficiency and Osteoporosis in Stroke Survivors: An analysis of National Health and Nutritional Examination Survey (NHANES) 2001-2006
Authors: Uluduz Derya , Adil Malik A , Rahim Basit , Rahman Haseeb A , Gilani Waqas I , Gilani Sarwat I , Qureshi Adnan I
Published: July 2021

INTRODUCTION:
Vitamin D deficiency might be involved in the development of several diseases including hypertension, diabetes mellitus and cardiovascular disease. An inverse association between 25(OH) D levels and stroke was also emphasized in recent studies.

Objective:
To determine the rate of vitamin D deficiency among stroke survivors and risk of associated osteoporosis in a nationally representative population.

Methods:
Participants from the National Health and Nutritional Examination Survey (NHANES) from 2001 through 2006 were included. Serum 25(OH) D levels were measured using the DiaSorin RIA kit (Stillwater MN) and history of previous stroke and osteoporosis was ascertained by standard interview. Stroke survivors were then divided into 2 groups depending on serum 25(OH) D levels: <30ng/dL as vitamin D deficiency and ≥30ng/dL as normal. Comparisons of demographics and risk factors between two groups were performed using the SAS software. Multivariate analysis was performed to determine the association between vitamin D deficiency and osteoporosis in stroke survivors after adjusting for potential confounding factors.

Results:
There were 415 (4.0%) stroke survivors among the total 10,255 participants in NHANES. The mean age [±SD] of stroke survivors was 67.56 [±17.3] years and 211 (50.8%) were men. Mean 25(OH) D concentrations were found to be not significantly different in patients with stroke (20.35 versus 21.82ng/mL, p=0.657) although the rate of osteoporosis was significantly higher among stroke survivors (17.92% versus 6.99%, p<0.0001). Out of 415 stroke patients, vitamin D deficiency was seen in 71.0% of the patients (mean concentration of 17.3±6.4ng/dL) and was normal in 29.0% patients (mean concentration of 34.6±5.3ng/dL). The rates of osteoporosis were similar between patients with or without Vitamin D deficiency. After adjusting for potential confounders, there was no association between vitamin D deficiency and osteoporosis.

Conclusion:
Vitamin D deficiency and osteoporosis are highly prevalent among stroke survivors, however, there does not appear to be a relationship between the two entities.
Abstract WP43: ‘Clinical-Diffusion Mismatch’ Triage Criteria at 8-24 Hours from Symptom Onset Identifies 4% of Stroke Patients for Potential Intervention
Authors: Janjua Nazli , Moradiya Yogesh , Bulic Sebina , Melkumova Emiliya
Published: July 2021

Background:
‘Clinical-diffusion mismatch’ (CDM) criteria may identify ischemic stroke (IS) patients with salvageable penumbra, and is intended for triage in a planned prospective trial of acute stroke intervention for patients presenting between 8 and 24 hours. For this study, CDM is defined as a National Institutes of Health Stroke Scale Score (NIHSSS) ≥8 and diffusion weighted imaging (DWI) stroke volume of ≤25 mL3 using a modified ‘ABC/2’ criteria, which has previously been validated against planimetric imaging and shown to have excellent inter-rater reliability. We sought to determine the percentage of potential patients who may be screened for enrollment on this basis in 2 urban teaching hospitals which each receive >200 stroke patients per year.

Methods:
We identified all IS admissions from our Get with the Guidelines database from 1/1/10-12/31/10. We then abstracted those arriving within 8 to 24 hours of symptom onset and then, of this subset, those who had an initial NIHSSS ≥8. To determine those meeting radiographic criteria, we measured stroke volume on the admission head computed tomogram (CT) using the unadjusted ABC/2 formula. As CT is known to have a 60% sensitivity for IS compared with DWI within 12 hours, we estimated that only 60% of the patients from the above calculation might still have lesion volumes ≤25mL3 on DWI.

Results:
A total of 588 IS patients were admitted in 2010. Of these, 162 patients presented within 8-24 hours. NIHSSS were ≥8 in 41 of whom 28 had lesions ≤25mL3. Considering 60% of these would remain valid on DWI, would leave approximately 17 patients (2.6%). Incomplete data led to attrition at each step; applying the same percentages at each recruitment step to those lost yields 9 patients, for an overall potential recruitment of 26 (4.4%, table).

Conclusion:
We conservatively estimate that in 1 year, 4% of IS patients within 8-24 hours demonstrate a CDM. These data are important for trialists and funding agencies planning studies using CDM criteria.
Abstract WP55: A Comparison of Outcomes in Patients Selected for Endovascular Stroke Treatment with and without the Aid of CT Perfusion Imaging
Authors: Ferenz Gregory , Reichwein Raymond
Published: July 2021

Background:
Selection of patients for endovascular stroke treatment has traditionally been based on time since symptom onset. CT perfusion (CTP) imaging has raised the possibility of patient selection on objective measures other than time from stroke onset. However, previous studies have failed to show significant outcome improvement in patients selected for endovascular stroke treatment based on CTP, but have been limited by small sample size, lack of outcomes past time of discharge, or lack of control group.

Objective:
To determine if endovascular stroke treatment selection with the aid of CTP is associated with improved clinical outcomes at 90 days as compared to patients undergoing endovascular stroke treatment without the aid of CTP.

Methods:
This study retrospectively reviewed a prospectively collected database of all patients who underwent endovascular stroke treatment at Penn State Hershey Medical Center between 1/1/2009 and 12/31/2011. Patients with posterior circulation strokes and those enrolled in other treatment trials were excluded. Patients were divided into two groups based on whether they had undergone a CTP study prior to endovascular stroke treatment or not. The variables measured included age, sex, and NIHSS on admission. Outcome data measured from the patients 90 day post stroke follow up appointments included an NIHSS improvement by 4 or more, a modified Rankin Score (mRS) of 2 or less, and mortality.

Results:
Of 41 patients included in the study, there was no significant difference in outcomes at 90 days as measured by an improvement of NIHSS of 4 or more (p=0.106) or modified Rankin score of 0-2 (p=0.475). Table 1 summarizes the results.

Conclusion:
Endovascular stroke treatment selection with the use of CTP was not associated with improved clinical outcomes at 90 days as measured by NIHSS improvement of 4 or more or a mRS of 0-2.
Abstract WP94: Delayed SDF-1 Hyperexpression Promotes Neural Stem Cell Migration and Maturation without Increasing Inflammation after Ischemic Stroke in Mice
Authors: Li Yaning , Huang Jun , He Xiaosong , Tang Yaohui , Lv Yifan , Tang Guanghui , Yang Guoyuan , Wang Yongting
Published: July 2021

Background and purpose:
SDF-1 has double-edged function after ischemic stroke. It can attract both inflammatory cells and neural stem cells (NSC). However, the action of SDF-1 in regulating neural stem cells migration and maturation during post-ischemic stroke is unclear. Here we used adeno-associated virus (AAV) to deliver SDF-1 gene into the peri-infarct area one week after permanent middle cerebral artery occlusion (MCAO) to investigate the effect of SDF-1 on endogenous NSC migration and maturation.

Methods and materials:
Twenty-four adult ICR male mice received AAV carrying SDF-1 or GFP gene transfer into the peri-infarct area one week after MCAO. Brain atrophy volume, neurobehavioral tests and immunohistochemistry were performed to evaluate the effects of SDF-1 on endogenous NSC migration, maturation and neuronal function repair.

Results:
SDF-1 was highly expressed in peri-infarct area for at least four weeks after gene transfer. Brain atrophy volume was significantly reduced in AAV-SDF-1 group compared to AAV-GFP gourp (
p
<0.05). The results of neurobehavioral tests including neurological deficits and rotarod test paralleled the result of atrophy volume, with neuronal function greatly improved in AAV-SDF-1 group (
p
<0.05). Immunohistology showed that the number of nestin and doublecortin positive cells in peri-infarct area was significantly increased in AAV-SDF-1 group in contrast to AAV-GFP group (
p
<0.05). In addition, there was no difference in myeloperoxidase positive cells in ischemic peri-infarct area between AAV-SDF-1 and AAV-GFP group (
p
>0.05).

Conclusion:
Our results demonstrated that SDF-1 gene therapy significantly increased NSC migration and maturation without increasing focal inflammatory response; consequently reduced brain atrophy volume and improved the neurological outcomes of animals, suggesting that delayed SDF-1 hyperexpression plays a key role in neurogenesis and neural repair. These
in vivo
results indicate that SDF-1 holds great potential as a stem cell chemotactic factor in the treatment of ischemic stroke.
Abstract 12: S-Nitrosylation Invokes Functional Recovery from Experimental Stroke through the Hypoxia-inducible Factor-1 alpha/Vascular Endothelial Growth Factor Pathway
Authors: Khan Mushfiquddin , Dhammu Tajinder S , Matsuda Fumiyo , Singh Inderjit , Singh Avtar K
Published: July 2021

Background:
In stroke patients, the stimulation of neurorepair mechanisms is necessary to reduce morbidity and disability. Our studies on brain and spinal cord trauma show that an exogenous treatment with the S-nitrosylating agent S-nitrosoglutathione (GSNO) stimulates neurorepair and aids functional recovery. Using a rat model of cerebral ischemia reperfusion (IR), we tested the hypothesis that GSNO invokes the neurorepair process and improves neurobehavioral functions through the angiogenic HIF-1α/VEGF pathway.

Methods:
Stroke was induced by middle cerebral artery occlusion for 60 min followed by reperfusion in adult male rats. The injured animals were treated with vehicle (IR group, n=7), GSNO (0.25 mg/kg, GSNO group, n=7), and GSNO plus the HIF-1α inhibitor 2-mthoxyestradiol (0.25 mg/kg GSNO+5.0 mg/kg ME, GSNO+ME group, n=7). The groups were studied for 14 days to determine neurorepair mechanisms and functional recovery. Brain capillary endothelial cells were used to show that GSNO promotes angiogenesis and that GSNO-mediated induction of VEGF and the stimulation of angiogenesis are dependent on HIF-1α activity.

Results:
GSNO treatment of IR enhanced the expression of HIF-1α, VEGF, and PECAM-1. This GSNO treatment also led to increased expression of neurorepair mediators including BDNF. Increased expression of VEGF/BDNF and the degree of tube formation (angiogenesis) by GSNO were reduced in an endothelial cell culture model after the inhibition of HIF-1α by ME. ME treatment of the GSNO group also blocked not only GSNO’s effect of reduced infarct volume (p<0.05) and enhanced expression of PECAM-1but also its improvement of motor and neurological functions (p<0.001).

Conclusions:
GSNO shows therapeutic promise for stroke by stimulating the process of neurorepair and aiding functional recovery through the HIF-1α/VEGF/PECAM-1 dependent pathway.
Abstract 126: Comparison of Flow Diversion and Coiling in Large Unruptured Intracranial Saccular Aneurysms
Authors: Chalouhi Nohra , Tjoumakaris Stavropoula , Starke Robert M , Gonzalez L Fernando , Randazzo Ciro , Hasan David , Singhal Saurabh , Dumont Aaron S , Rosenwasser Robert , Jabbour Pascal
Published: July 2021

Background and purpose:
Flow diversion has emerged as an important tool for management of intracranial aneurysms. The purpose of this study was to compare flow diversion and traditional embolization strategies in terms of safety, efficacy, and clinical outcomes in patients with unruptured, large saccular aneurysms (≥ 10 mm).

Methods:
Forty patients treated with the Pipeline Embolization Device (PED) were matched in a 1:3 fashion with 120 patients treated with coiling based on patient age and aneurysm size. Fusiform and anterior communicating artery aneurysms were eliminated from the analysis. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared.

Results:
There were no differences between the 2 groups in terms of patient age, gender, aneurysm size, and aneurysm location. The rate of procedure-related complications did not differ between the PED (7.5%) and the coil group (7.5% p=1). At the latest follow-up, a significantly higher proportion of aneurysms treated with PED (86%) achieved complete obliteration compared to coiled aneurysms (41%, p<0.001). In multivariable analysis, coiling was an independent predictor of nonocclusion. Retreatment was necessary in fewer patients in the PED group (2.8%) than the coil group (37%, p<0.001). A similar proportion of patients attained a favorable outcome (mRS 0-2) in the PED group (92%) and the coil group (94%, p=0.8).

Conclusion:
The PED provides higher aneurysm occlusion rates than coiling, with no additional morbidity and similar clinical outcomes. These findings suggest that the PED is a preferred treatment option for large unruptured saccular aneurysms.
Abstract 14: Synaptic Remodeling after Stroke Enhanced by Transplanted Human Neural Stem Cells is Coincident with Functional Recovery
Authors: Hiu Takeshi , Bliss Tonya , Manley Nathan , Wang Eric , Nishiyama Yasuhiro , Sun Guohua , Olson Andrew , Micheva Kristina , Wang Gordon , Berry Jack , Smith Stephen , Steinberg Gary
Published: July 2021

Background:
Stem cell transplantation (Tx) has emerged as a promising new experimental treatment for stroke; understanding its mechanism of action will facilitate the translation of stem cell therapy to the clinic. The ultimate change in brain plasticity is manifested at the synaptic level, however, the synaptic remodeling after stem cell therapy remains unknown. Here we evaluate the effect of transplanted human neural progenitor cells (hNPCs) on the peri-infarct synaptic remodeling in the post-ischemic brain.

Materials and Methods:
We use array tomography, a high-resolution proteomic imaging method, to determine how hNPCs affect the number and subtype of glutamate and GABA synapses after stroke. Vehicle or hNPCs were transplanted into the ischemic cortex of Nude rats 7 days after distal middle cerebral artery occlusion. Neurological recovery was assessed weekly using a battery of behavioral tests. The arrays of serial ultrathin sections (70 nm), removed from the peri-infarct cortex at 1 and 4 weeks post-Tx, were stained using multiple synaptic markers and imaged in cortical layer 2/3 and 5. Computational analysis of the resultant staining pattern was used to identify and quantify subtypes of glutamate and GABA synapses.

Results:
Tx of hNPCs significantly improved behavioral recovery after stroke compared to vehicle-treated rats (4 weeks post-transplantation; p<0.01) without altering the infarct size. hNPC-treated rats had a higher density of VGluT1-containing glutamate synapses (0.223 vs 0.185 synapses/μm3, p<0.05), and GluA2-containing glutamate synapses (0.091 vs 0.069 synapses/μm3, p<0.05) in layer 5 at 4 weeks post-Tx, compared to vehicle-treated rats. However, hNPCs had did not alter total number of glutamate synapses. This synaptic increase was cortical layer-specific observed in layer 5 but not .in layer 2/3. hNPCs had no detectable effect on the density of GABA synapses in either layer 5 or 2/3 at 1 week or 4 weeks post-Tx.

Conclusions:
These results provide novel new information about the organization of synaptic circuitry and its plasticity after stem cell therapy. These data suggest that stem cells alter the subunit composition of glutamate synapses after stroke and this is coincident with stem cell-induced functional recovery.
Abstract 176: Long Term Mortality in Acute Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation According to Location and Burden of Cerebral Microbleeds
Authors: Song Tae-Jin , Kim Jinkwon , Song Dongbeom , Kim Yong-Jae , Nam Hyo Suk , Kim Young Dae , Heo Ji Hoe
Published: July 2021

Background:
Cerebral microbleeds (CMBs) were predictive of mortality in elderly and considered as a putative marker for risk of intracranial hemorrhage. Stroke patients with non valvular atrial fibrillation (NVAF) require anticoagulation, which increases the risk of hemorrhages. We investigated association of CMBs with the long term mortality in acute ischemic stroke patients with NVAF.

Methods:
During 6 years
,
consecutive ischemic stroke patients who had NVAF and who had undergone brain MRI with a gradient-recalled echo sequence were enrolled. Long-term mortality and causes of death were identified using data from Korean National Statistical Office. Survival analysis was performed whether the presence, number and location of CMBs were related with all causes, cardiovascular, and cerebrovascular mortality during follow-up.

Results:
Total 506 patients were enrolled during the study period and were followed up for median 2.5 years. CMBs were found in 30.8% of patients (156/506). Oral anticoagulation with warfarin was prescribed at discharge in 477 (82.7%) patients. During follow up, 177 (35%) patients died and cerebrovascular death was noted in 93 patients (81 ischemic stroke and 12 hemorrhagic stroke). After adjusting age, sex and significant variables in univariate analysis (p<0.1), multiple CMBs (≥5) were the independent predictor for all-cause, cardiovascular and ischemic stroke mortalities. The strictly lobar CMBs were associated with hemorrhagic stroke mortality in multivariate Cox regression analysis (HR 4.776, p=0.032) (Figure 1).

Conclusions:
Multiple CMBs were the independent predictor for the long term mortality in stroke patients with NVAF. Among them, patients with strictly lobar CMBs had a high risk of death due to hemorrhagic stroke. Our findings suggest that detection of CMBs in stroke patients with NVAF are of clinical relevance for predicting long term outcome and that particular concern is necessary in those with strictly lobar CMBs for their increased risk of death due to hemorrhagic stroke.

Figure 1.
Abstract 187: Impact of General Anesthesia on Safety and Outcomes in the Endovascular Arm of IMS III
Authors: Abou-Chebl Alex , Hill Michael D , Yan Bernard , Cockroft Kevin , Khatri Pooja , Meyers Phillip M , Spilker Judith , Sugg Rebecca M , Wartenberg Katja E , Yeatts Sharon D , Tomsick Tom A , Broderick Joseph P
Published: July 2021

Objectives:
Use of general anesthesia (GA) during endovascular therapy (ET) of AIS patients is controversial with some suggestion of worse outcomes and death. The IMS III trial permitted the study of the effect of GA in a prospectively collected data set to test two hypotheses: (1) intubation is associated with poorer outcomes and (2) there is no increase in the risk of SAH or sICH with local anesthesia (LA).

Methods:
IMS III was a randomized trial of IV tPA +/- ET in patients presenting within 3hrs of AIS onset. In addition to demographic and outcomes data (mRS, ICH, etc.), information was collected on GA use or not within 7hrs of stroke onset. A good outcome was defined as mRS≤2 at 90 days. A multivariable analysis adjusting for dichotomized NIHSS (8-19 vs. ≥20), age and time from onset to groin puncture was performed. Additional analyses of reasons for intubation are ongoing and will be part of the presentation.

Results:
Four-hundred-thirty-four patients were randomized to ET, 269(62%) with LA and 147(33.9%) with GA. They were evenly matched in demographics, medical comorbidities, time to tPA, time to groin puncture, 40minute post IV tPA bolus SBP and occlusion location/side. The baseline NIHSS were slightly lower in the LA group (median 16 vs. 18). The GA group was less likely to achieve a good outcome (RR 0.64, CI 0.49-0.84, p=0.001) and had a greater risk of in-hospital death (RR 3.11, CI 1.86-5.20, p<0.0001). There was an increased risk of SAH in the GA group (RR 1.79, CI 1.04-3.08, p=0.0364) but no statistically significant difference in sICH (RR 1.69, CI 0.79-3.61, p=0.18). The multivariable analysis confirmed the negative association between GA and good outcomes (RR 0.68, CI 0.52-0.90, p=0.0027).

Conclusions:
In the IMS III trial there was an association with worse neurological outcomes and increased mortality with ET under GA. Also, there was an association between GA and an increased risk of SAH. Although the reasons for these associations are not clear, these data support the use of LA when possible during ET.
Abstract 188: Correlation of Angiographic Capillary Index Score (CIS) with Diffusion and Perfusion MR Imaging in the DEFUSE 2 Trial
Authors: Marks Michael P , Al-Ali Firas , Lansberg Maarten G , Mlynash Michael , Kemp Stephanie M , Zaharchuk Greg , Bammer Roland , Albers Greg W
Published: July 2021

Objective:
The CIS has been shown to be a predictor of good clinical outcome following endovascular therapy for acute ischemic stroke. We undertook this study to determine the relationship between CIS and baseline diffusion-perfusion imaging as well as angiographic collaterals in DEFUSE 2 study patients.

Methods:
Patients undergoing endovascular therapy within 12 hours of stroke onset were prospectively enrolled. Only patients with an ICA/M1 occlusion and adequate demonstration of the anterior and posterior circulations at baseline angiography were included in this analysis. Blinded reading of the CIS was made using a 4 point scale from 0 (no capillary blush in ischemic territory) to 3 (blush throughout). Analysis was dichotomized to poor CIS (0-1) versus good (2-3). CIS was correlated with baseline DWI volume, PWI volume (Tmax > 6, Tmax>10), an angiographic collateral score (using a previously described 5 point scale) and subsequent infarct growth.

Results:
Forty-eight patients had ICA/M1 occlusions and adequate angiographic images to evaluate CIS. Baseline DWI lesion volume correlated with CIS (p=0.001). Median DWI volume for patients with poor CIS (0-1) was 28 (IQR, 11-54) versus 13 (3-27) for those with good CIS (2-3), p=0.011. Baseline T max > 6 volume correlated with CIS (p=0.004). Median volume of tissue at risk (T max > 6 sec) in those with poor CIS was 108 ml (IQR, 74-138) versus 69(43-108) with good CIS, p=0.009. Severe T max delay (> 10 sec) also correlated with CIS (p=0.001). CIS was also found to correlate with angiographic collaterals (p=0.006). On follow-up MRI CIS correlated with subsequent lesion growth (p=0.043).

Conclusions:
CIS provides a rapid angiographic assessment of capillary blush from collateral flow into the ischemic territory and correlates with angiographic collateral scores. In DEFUSE 2 the CIS score was strongly associated with baseline DWI and PWI lesion volumes and subsequent lesion growth.
Abstract 202: Door-to-needle-time at 20 Minutes is Feasible and Safe
Authors: Henriksen Sille M , Jeppesen Lise L , Christensen Anders , Christensen Hanne K
Published: July 2021

Background:
Effect size of intravenous fibrinolysis in acute stroke depends on time to treatment, while safety depends on a systematic identification of risk factors for bleeding complications. Fibrinolysis is in Denmark the treatment with most potential of modifying outcome in acute stroke patients both in a quantitative and qualitative perspective. We initiated a quality project aiming at reducing our median door-to-needle-time (DTN). The aim of this study was to obtain median DTN below 20 minutes accepting no increase in bleeding complications.

Method:
A team including neurologist, radiologist, stroke nurse and radiographer set up a structured patient admission process based on trauma team principles and experience with fibrinolysis. The team has immediate access to both CT and MRI; standard work up is CT + CTA. EMS informs of patients with likely symptoms of acute stroke and the patient is received by the team in a dedicated room. During a 3-month registration period from March to June 2013 an external person registered all cases of acute stroke evaluation. The registration covered time of symptom onset, time of arrival, needle time or decision of no thrombolysis and the distribution of the time used e.g. for blood sampling or CT. For comparison, data from our institution in 2012 was used.

Results:
A total of 157 patients were evaluated and 148 patients were registered; nine patients (5,7%) missed time registration, however no significant difference in thrombolysis ratio was found between the missing and registered group (p=0,473). Patients had a median age of 67 years and 53,4% was male. Forty-seven patients (31,8%) received fibrinolysis. The overall median time is 16 minutes 58 seconds. For patients receiving fibrinolysis, the DNT was 20 minutes 58 seconds and for patients not receiving treatment the median time to desiscion was 15 minutes 50 seconds. No symptomatic intracranial hemorrhages or other significant bleeding complications occured during the study period. Median DTN in 2012 was 49 minutes. Costs were neutral.

Conclusion:
DTN time can be reduced to 20 minutes by organizational interventions with no apparent effect on safety. NNT is reduced by 1 with every 20 minutes reduction in DTN so this intervention is likely to be highly clinically significant.
Abstract 54: Procalcitonin, Copeptin and Midregional Pro-atrial Natriuretic Peptide as Markers of Ischemic Stroke Risk: The Northern Manhattan Study
Authors: Katan Mira , Moon Yeseon P , DeRosa Janet , Paik Myunghee C , Mueller Beat , Herklotz Roberto , Sacco Ralph L , Elkind Mitchell S
Published: July 2021

Background:
Chronic infections and neuroendocrine dysfunction may be risk factors for ischemic stroke. We hypothesized that selected blood biomarkers of infection (procalcitonin, or PCT), hypothalamic-pituitary-axis function (copeptin), and hemodynamic stress (midregional pro-atrial natriuretic peptide, or MRproANP) would be associated with incident ischemic stroke risk in the multi-ethnic, urban Northern Manhattan Study (NOMAS) cohort.

Methods:
A case-cohort study was performed among initially stroke-free participants from the prospective population-based NOMAS study. The mean follow up was 11 years. Cases were defined as first ischemic stroke (including fatal) with available baseline blood (n=172). We randomly selected controls among those who did not develop an event (n=344). Biomarkers were measured in a blinded batch analysis (Laboratory of the Medical University Clinic, Aarau, Switzerland, using B.R.A.H.M.S assays by Thermo Fisher Scientific). We calculated hazard ratios and 95% confidence intervals (HR, 95% CI) using Cox proportional hazards models, with inverse probability weighting to correct for the case-cohort study design, to estimate the association with risk of stroke after adjusting for demographic, behavioral, and medical risk factors.

Results:
Mean age of cases was 72 (IQR 65-78); 59% were female. After full adjustment, those with PCT in the top quartile, compared to the lowest quartile, were at increased risk of ischemic stroke (adjusted HR 1.98, 95% CI 1.02-3.83). Those with MRproANP levels in the top quartile, compared to the lowest quartile, were also at increased risk of stroke (adjusted HR 3.45, 95% CI 1.58-7.52), but not those with higher copeptin levels. The distribution of MRproANP differed by stroke etiology. Levels of MRproANP were greater for cardioembolic strokes (CE), and MRproANP levels were predictive of CE (adjusted HR 3.29 per SD, 95% CI 1.89-5.72).

Conclusion:
Higher levels of procalcitonin, a marker of infection, and MRproANP, a marker for hemodynamic stress, were independently associated with ischemic stroke risk in this multiethnic, urban cohort. MRproANP was specifically associated with cardioembolic stroke risk. Further study is needed to confirm these results.
Abstract NS12: Stroke Mobile: Implementing A Novel Family Centered, Home-Based Post-Discharge System of Care
Authors: Jennings Bethany , Eckhardt Lynn , Egger Raymond , Batiquin Antonio , Bridges Aaron , Commiskey Patricia , Dadlez Gregory , Wennerstrom Ashley , Saucier Michael , Gaines Kenneth
Published: July 2021

Total annual costs of stroke-related care and loss of post-stroke productivity are projected to reach $241 billion by 2030, an increase of 129% since 2010. Although comprehensive stroke care programs have contributed to reductions in recurrent strokes, readmissions, and stroke-related complications, this population is vulnerable to non-adherence to the plan of care during the first year. Innovative in-home programs that coordinate team-based care hold promise for positively impacting this public health threat through greater emphasis on effective prevention, adherence, and optimizing outcomes.

Purpose:
The purpose of this project was to evaluate the implementation of a home-based post-discharge stroke mobile program to existing comprehensive stroke care.

Methods:
An inter-professional team of stroke specialists (physicians, advanced practice nurses, registered nurses), and administrative and financial specialists collaborated to develop an innovative, family-centered, home-based approach to post-discharge stroke care. The team identified project goals, assessment tools, and 12-month post-discharge outcome metrics. Telemedicine technology enabled a direct link between the mobile team, patient, and an APN or Neurologist to reduce office/emergency visits, and lower costs.

Results:
Training of the home-based team included stroke specific education, along with training in communication skills and family-based interventions. Home visits were structured to occur once per month for 1 year post stroke. Each visit was designed to impact specific elements related to enhancing physical recovery, preventing readmissions and stroke recurrence, improving medication compliance, risk factor management, and caregiver support. Fifteen of 24 (63%) received all scheduled visits, and all planned visits did not occur in 9/24 (37%) due to patient’s schedule. Only 2/24 (8%) were readmitted for stroke recurrence. Lessons learned include need to validate contact information before discharge; develop a brochure that targets program enrollment; and explore options to visit in other settings.

Conclusion:
A family centered, home-based, post-discharge system of care is a viable solution to addressing the complex needs of the stroke patient.