bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP90: Race/Ethnic Disparities in Short and Long Term Mortality Among Medicare Beneficiaries in Florida and Puerto Rico: Data from the Florida Puerto Rico Collaboration to Reduce Stroke Disparities (FL-PR CReSD) Study - the NINDS Stroke Prevention Intervention Research Program
Authors: Gardener Hannah , Leifheit-Limson Erica C , Lichtman Judith , Wang Yun , Wang Kefeng , Gutierrez Carolina M , Ciliberti-Vargas Maria A , Dong Chuanhui , Robichaux Mary , Romano Jose G , Rundek Tatjana , Sacco Ralph L ,   for the FL-PR CReSD Investigators and Collaborators
Published: June 2021

Background:
Race/ethnic disparities in acute stroke care may impact stroke outcomes. We compared short- and long-term mortality by race/ethnicity among Medicare beneficiaries in Get With The Guidelines (GWTG) hospitals participating in the NINDS-funded prospective Florida Puerto Rico Collaboration to Reduce Stroke Disparities Registry (GWTG/CReSD), GWTG hospitals not in the Registry (GWTG/non-CReSD), and non-GWTG hospitals not in the Registry (non-GWTG/non-CReSD).

Methods:
The population included Medicare beneficiaries age 65+ in FL and PR, hospitalized from 2010-2013 with ischemic stroke (ICD-9 433, 434, 436; N=105,205, mean age=80 years, 54% women). We used mixed logistic models adjusted for demographic and clinical characteristics to assess race/ethnic differences in in-hospital, 30-day, and 1-year mortality, stratifying by hospital type (GWTG/CReSD, GWTG/non-CReSD, non-GWTG/non-CReSD).

Results:
In the 62 GWTG/CReSD hospitals (N=44013, 84% non-Hispanic White (NHW), 9% NH-Black (NHB), 4% FL-Hispanic (FLH), 1% PR-Hispanic (PRH)), NHB had lower 30-day mortality vs NHW (10% vs 12%; OR 0.86, 95% CI 0.77-0.97), but higher 1-year mortality (22% vs 20%; OR 1.13, 95% CI 1.04-1.23); there were no race/ethnic disparities for in-hospital mortality (NHB=6%, NHW=5%, FLH=7%, PRH=12%). However, in 74 GWTG/non-CReSD hospitals (N=46770, 88% NHW, 8% NHB, 2% FLH, 0% PRH), FLH (5%) and NHB (4%) had higher in-hospital mortality vs NHW (3%). For 113 non-GWTG/non-CReSD hospitals (N=14422, 78% NHW, 7% NHB, 5% FLH, 8% PRH), in-hospital mortality was higher for PRH (17%) and NHB (8%) vs NHW (5%). In-hospital and 1-year mortality were lower in CReSD and in GWTG/non-CReSD vs in non-GWTG/non-CReSD hospitals.

Conclusions:
FL and PR Medicare beneficiaries treated for stroke in GWTG hospitals (both GWTG/CReSD and GWTG/non-CReSD) had lower mortality vs those treated in non-GWTG hospitals; however, there were less race/ethnic disparities in in-hospital mortality for stroke patients treated at GWTG/CReSD hospitals, which are focused on reducing disparities in acute stroke care. Findings underscore the benefits of quality improvement programs, particularly those focusing on race/ethnic disparities.
Abstract WMP96: Stroke Warning Signs In Spanish Speaking Communities: Camaleon Strategy Proposal
Authors: Barboza Miguel A , Agüero Cinthya , Bastos Paola , Fernández Huberth
Published: June 2021

Introduction:
early recognition of stroke signs lead to a better opportunity for acute management, to decrease morbidity and mortality impact. Public awareness campaigns have been developed with English language acronyms for recognition of these signs, but language and cultural differences should be taken into account for these educational strategies.

Hypothesis:
we assessed the hypothesis that there is a need for a validated tool for Spanish speaking population for early recognition of stroke warning signs.

Material and methods:
a 12-item electronic and paper-based survey for non-health related professionals evaluated the knowledge of early stroke signs in a Costa Rican sample. Using data from the FAST acronym, we developed a Spanish based acronym focused on the 3 most common symptoms, which was evaluated with medical professionals and non-medical population for clarity of message and informative content through a 10-item survey.

Results:
706 non-medical professional subjects answered the evaluation survey (56.7% female, median age 33 years [IQR 24-43 years]), with 76.2% answering that they were not capable of diagnose an acute stroke, and 97.2% considering the necessity of develop an educational campaign for acute stroke signs recognition. CAMALEON acronym (CAra [face], MAno/brazo [hand/arm], LEnguaje [language] and teléfONo [telephone]) was created adapting FAST acronym to Spanish. 25 medical professionals evaluated the medical content of the Spanish acronym (based on an educational video) with a 95% of acceptance of its content to explain medical symptoms; also 91% of 100 non-medical subjects were able to recognize adequately the symptoms after viewing the video material. This academic initiative is endorsed by the World Stroke Academy from the World Stroke Organization.

Conclusion:
CAMALEON strategy is an adequate acronym for early recognition of acute stroke signs for Spanish speaking countries that should be validated in stroke awareness campaigns.
Abstract WMP97: Acute Cerebral Ischemia After Aggressive Blood Pressure Reduction in Primary Intracerebral Hemorrhage: How Low Can You Go?
Authors: Thacker Tapan , Buletko Andrew , Mathew Jason , Organek Natalie , Hussain Muhammad Shazam , Frontera Jennifer , Uchino Ken
Published: June 2021

Introduction:
Despite studies of aggressive blood pressure reduction in primary intracerebral hemorrhage (ICH), the potential for inducing ischemia remains a concern. The primary objective of this study is to determine the relationship between blood pressure and acute cerebral ischemia following ICH.

Methods:
We performed a retrospective chart review of patients with primary ICH admitted between January 2013 and December 2014 in whom MRI brain with diffusion-weighted imaging (DWI) was performed within 2 weeks of admission. Acute ischemia was defined as DWI hyperintensity with corresponding apparent diffusion coefficient hypointensity. Lesions adjacent to the ICH or after an invasive procedure were excluded and all MRIs were performed prior to digital subtraction angiography. Serial blood pressure measurements were collected from admission to 72h post ictus. Clinical deterioration was defined as any acute exam change not explained by seizure, hematoma expansion or other medical causes.

Results:
Among 119 patients with primary ICH (mean age 69.3 years, 58% males, 65% Caucasians), 28 (23.5%) had acute ischemia. Acute ischemia was associated with lower mean 24-hour SBP (132 mmHg in DWI+ versus 141 mmHg in DWI-, p<0.001), greater mean change in SBP from admission to 24 hours (67 mmHg in DWI+ versus -42 mmHg in DWI-, p=0.002), lower mean minimum SBP at 72 hours (104 mmHg in DWI+ versus 111 mmHg in DWI-, p=0.008) and lobar ICH location (35% in DWI+ versus 14% in DWI-, p=0.009). Minimum SBP <120 mmHg during the first 72 hour after ICH has a sensitivity of 96% in predicting DWI lesions in patients with ICH (p=0.014). Overall, patients with DWI+ lesions had a higher incidence of clinical deterioration (32% in DWI+ versus 6% in DWI-, p<0.001) and longer length of stay compared to patients without DWI lesions (13 days in DWI+ versus 8 days in DWI-, p=0.006). Hematoma volume, initial NIH Stroke Scale and admission SBP were not significantly associated with DWI lesions in patients with primary ICH.

Conclusions:
Aggressive SBP reduction, particularly SBP<120 mmHg within the first 72h of ICH, can be associated with acute cerebral ischemia. A third of acute ischemic lesions are associated with clinical deterioration.
Abstract WP107: Igf-1-mediated Neuroprotection for Ischemic Stroke is Preceded by Its Actions at the Endothelial Cell Barrier
Authors: Bake Shameena , Okoreeh Andre , Sohrabji Farida
Published: June 2021

Background:
Our studies show that Insulin like growth factor (IGF)-1 reduces MCAo-induced infarction in middle-aged female rats. We tested the hypothesis that IGF-1s neuroprotective effect is due to its action on the microvascular /endothelial barrier in the early acute phase of stroke.

Methods:
Middle-aged (12 mo) acyclic female rats were subject to intraluminal middle cerebral artery occlusion (MCAo) for 90 min followed by reperfusion and terminated 4h or 24h later. Animals received ICV infusion of artificial CSF, IGF-1 or IGF-1+JB-1. In separate experiments, we evaluated infarct volume, barrier assessment by uptake of Evan’s blue dye or histological evaluation of lectin stained microvessels. In parallel, cortical endothelial cells from middle-aged females were harvested and cultured ex vivo. Barrier properties were tested in cultures in transfer wells exposed to oxygen glucose deprivation (OGD) in the presence or absence of IGF-1 with FITC-labeled BSA in the media.

Results:
At 4h post MCAo, IGF-1 treatment significantly reduced brain uptake of Evan’s blue dye, while infarct volume was no different from controls. At 24h post MCAo, IGF-1 reduced infarct volume by 40% and decreased motor impairment (neurological score; p<0.05). Lectin stained microvessels in the ischemic hemisphere displayed wider lumens (normal uncompressed lumen, p<0.003) and more intense label (p<0.01) in IGF-1 treated animals as compared to either vehicle or IGF-1+JB-1 groups. Ex vivo, IGF-1 reduced the loss of cell-cell contact due to OGD and reduced the dye transfer across the monolayer.

Conclusions:
Our findings indicate that IGF-1 acts in the early acute phase of ischemic stroke to reduce barrier permeability, which precedes its beneficial effect on infarct volume and behavior. Further, brain endothelial cells play a crucial role in

IGF-1 mediated neuroprotection in middle-aged females.
Abstract WP110: Identification and Validation of a Unique Mirna Target Mir-141-3p in Post Stroke Socially Isolated Aged Mice
Authors: Verma Rajkumar , McCullough Louise D
Published: June 2021

Introduction:
MicroRNAs (miRNAs) are a class of short non-coding RNAs that have been identified as a powerful interventional tool for many diseases, including stroke. Very recent studies have found that microRNAs also mediate aspects of social interaction. Social environments can directly influence miRNA expression, which then triggers a plethora of downstream gene changes. Social isolation (SI) impairs stroke recovery and leads to inflammation. We hypothesize that miRNAs are involved in the detrimental effects of post-stroke social isolation.

Methods:
Eighteen-month-old male C57BL/6 mice were pair housed (PH) for two weeks prior to stroke and randomly assigned to various housing conditions (ST-ISO or ST-PH) immediately after stroke (ST). Mice were sacrificed either at 3, 7 or 14 days after 60-minute right MCAO or sham surgery (n=4-6/group) and perilesional frontal cortex was isolated for miRNA analysis. Total RNA was isolated using either Qiagen miRNeasy® Mini Kit/ miRVANA miRNA isolation kit (Ambion, Life technologies). Whole miRNOme analysis of total RNA isolated from brain tissue was performed using miRCURY LNA
TM
Universal RT microRNA. Post-treatment with an ‘in vivo ready’ antagomir of miR-141-3p (7mg/kg i.v/day x 3 days; n=4/group) was given through lateral tail veins.

Results:
Using whole miRNOme analysis of approx. 800 miRNA, we found miR-141-3p was a unique miRNA whose expression was significantly upregulated in a time dependent manner up to day 14 after stroke. The post treatment with an ‘in vivo ready’ antogomir of miR-141-3p reduced the isolation-induced increase in miR-141-3p to levels almost equal to that of pair-housed controls. Post- treatment significantly reduced mortality (by 21% as compared to -ve control) and sensory motor deficits after stroke. mRNA targets analysis study using qPCR confirmed the significant (p<0.05 vs Neg Control ) upregulation of target several genes like arg-1, ccl22 and TGFbr1, markers of M2 type microglial activation, after antogomir treatment.
Summary:
The present data suggests the unique role of miR-141-3p in post stroke isolation. Temporal expression profiling studies suggest its validation as a potential targets. Post treatment data confirms the
in vivo
feasibility of miRNA modulation after stroke.
Abstract WP115: Transplanted Induced Neural Stem Cells Differentiate and Integrate Into the Brain Parenchyma of Ischemic Stroke Pigs Leading to Improved Tissue Recovery
Authors: Baker Emily W , Platt Simon R , Holmes Shannon P , Wang Liya , Lau Vivian W , Grace Harrison E , Kinder Holly A , Howerth Elizabeth W , Duberstein Kylee Jo J , Stice Steven L , Hess David C , Mao Hui , West Franklin D
Published: June 2021

Studies in rodents have provided evidence that induced pluripotent stem cell derived neural stem cells (iNSCs) have a multifunctional role in stroke recovery. iNSCs mitigate tissue loss due to secondary injury, promote tissue recovery through angiogenesis, and differentiate into mature neural cell types resulting in recovery and replacement of lost and damaged brain tissue. However, many stroke therapies developed in the rodent have failed in clinical trials, suggesting that iNSC therapy should be tested in a more translatable large animal model such as the pig. The objective of this study was to assess the ability of iNSCs to differentiate into mature neural cell types and characterize the effects of iNSCs on brain tissue recovery utilizing non-invasive magnetic resonance imaging (MRI) and spectroscopy approaches in a pig model. Eight male landrace pigs underwent middle cerebral artery occlusion stroke surgery. After 5 days, 4 pigs received iNSC intraparenchymal injections and 4 pigs received vehicle only injections. Pigs underwent MRI assessment at 24 hrs post-stroke and 1, 4, and 12 wks post-injection, and brain tissues were collected 12 wks post-injection. At 12 wks post-injection, iNSC treated pigs showed significant improvement in white matter integrity with recovery of fractional anisotropy being 4-fold higher in treated pigs relative to non-treated pigs. Perfusion weighted imaging demonstrated significant improvement in cerebral blood volume (13%), time to peak (36%), and mean transit time (41%) in treated pigs at 12 wks post-injection vs. non-treated pigs. In addition, treated pigs showed significant improvement in neurometabolites NAA, Cr, and Cho at 12 wks post-injection relative to non-treated pigs. Gene expression analysis established significant increases in neurotrophic and angiogenic factors including BDNF and ANG1, respectively, in brain tissue of treated pigs vs. non-treated pigs suggesting potential modes of action. iNSCs were located in the brain parenchyma 12 wks post-injection, and the majority were positive for the mature neuronal marker NeuN. These results demonstrated that iNSCs are capable of neuronal differentiation and long term integration while promoting tissue recovery in a preclinical pig ischemic stroke model.
Abstract WP118: Docosahexaenoic Acid Provides Neuroprotection by Increasing Neurogenesis After Experimental Stroke
Authors: Bazan Nicolas G , Khoutorova Larissa , Hong Sung-Ha , Menghani Hemant , Belayev Ludmila
Published: June 2021

Introduction:
Ischemic injury induces neurogenesis in the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of dentate gyrus (DG), and it promotes the migration of neuroblasts, guided by blood vessels, into the ischemic damaged area. Recently, we have shown that docosahexaenoic acid (DHA; 22:6n-3) therapy improves functional and histological outcomes following experimental stroke. The objective, hence, is to determine whether DHA administration enhances endogenous neurogenesis after cerebral ischemia.

Methods:
Twenty-one male SD rats were anesthetized with isoflurane and subjected to 2 h of middle cerebral artery occlusion (MCAo) by intraluminal filament. DHA (5 mg/kg, n=10) or saline (n=11) was administered intravenously at 3 h after onset of MCAo (n = 7-10 per group). BrdU was injected on days 4, 5 and 6. DCX (doublecortin), NeuN (a marker for mature neurons), ki-67 (marker for cell proliferation) have been used to test the proliferation, migration and differentiation of neural precursor cells. Behavioral tests were conducted on days 1, 2 and 3 and weeks 1 and 2. Immunohistochemistry with BrdU and ki-67, DCX or NeuN, and histopathology were performed on day 14.

Results:
DHA-treated animals showed improved neurologic scores compared to the saline group during the two-week survival period. Total, cortical and subcortical infarct areas in the DHA-treated group were significantly attenuated at multiple bregma levels as well as total, cortical and subcortical infarct volumes by 42.4 %, by 47.5 %, and by 31.2 % compared to the vehicle-treated group. The number of BrdU
+
/ki-67
+
cells in DHA-treated rats was increased in cortex by 88 %, SVZ by 40 % and DG by 270 % compared to saline-treated rats. DHA treatment increased the number of BrdU
+
/DCX
+
cells in the cortex by 65 %, the SVZ by 29 % and the DG (by 58 %) compared to saline-treated group. In addition, the numbers of BrdU
+
/NeuN
+
cells were increased in the cortex by 49 %, SVZ by 28 % and DG by 48% compared to vehicle treatment.

Conclusion:
DHA increased neurogenesis by proliferation, differentiation and migration of neural stem cells in the DG, SVZ and peri-infarct area two weeks after ischemic stroke. In addition, DHA promoted neurobehavioral recovery and reduced infarct volume.
Abstract WP119: Transcriptome Analysis of Motor Cortex Network Responses in Spontaneously Recovered Stroke Mice
Authors: Ito Masaki , Aswendt Markus , Cheng Michelle Y , Lee Alex G , Ishizaka Shunsuke , Wang Eric H , Smerin Daniel , Levy Sabrina , Steinberg Gary K
Published: June 2021

Introduction:
Spontaneous recovery after stroke occurs in both human and animals. However, the underlying molecular mechanisms driving spontaneous recovery are still unclear. This study investigates the molecular mechanisms driving spontaneous recovery after unilateral experimental stroke using RNA sequencing (RNAseq).

Methods:
Ischemic stroke was induced in C57BL/6J adult male mice by transient MCAO. Neurological score, vertical pole, and rotating horizontal beam test were performed at baseline and post stroke days (PD) 4, 8, and 14. All mice were sacrificed at PD15 and processed for immunohistochemistry or Hi-seq. Infarcts were visualized by T2WI at PD2 using 7T MR scanner or histology at PD15. All stroke mice included in the study have comparable cortico-striatal infarcts and exhibit similar prestroke baseline performance and PD4 deficits. These mice were further categorized into spontaneously recovered and non-recovered groups based on their rotating beam performance during recovery.

Results:
Out of 35 stroke mice with abovementioned similar conditions, 9 (26%) were categorized into spontaneously recovered group and 26 (74%) were categorized into non-recovered group. Hierarchical clustering analysis supported this categorization. At PD14, the spontaneously recovered group exhibited significant improvement in beam performance in distance traveled and speed (p<0.001). Using Ingenuity Pathway Analysis, the comparison of RNAseq transcriptome between ipsilesional and contralesional primary motor cortex (iM1 and cM1) in spontaneously recovered and non-recovered stroke mice revealed significant differential molecular pathways, including glutamate, calcium, and neurotrophin signaling pathways.

Conclusions:
Our study demonstrates that stroke mice with similar cortico-striatal infarct size can exhibit significant differences in their behavioral recovery outcome. The transcriptome profile in iM1-cM1 network at 2 weeks post-stroke highlighted several molecular pathways that were significantly different between spontaneously recovered and non-recovered mice. Validation of key molecular candidates from the RNAseq data would provide insights into the molecular mechanisms mediating spontaneous recovery after stroke.
Abstract WP122: Heterochronic Parabiosis Reverses the Epigenetic Imbalance of the Aged Central Nervous System
Authors: Koellhoffer Edward C , Morales-Scheihing Diego , d’Aigle John , McCullough Louise D
Published: June 2021

Background:
Microglia, the innate immune cells of the central nervous system (CNS), are the first cellular responders to stroke. Microglia populate the brain during development and age throughout the life of the individual. With aging, microglia transition to an activated, pro-inflammatory phenotype, making them primed to respond in a malicious manner following an ischemic event. These primed microglia are the same cells that populated the brain during development but now have an altered gene expression profile due to the inflammaging environment (e.g. cell damage, inflammatory cytokine milieu). Cells, including microglia, may respond to inflammaging by altering their epigenetic landscape to ultimately result in changes in gene expression.

Hypothesis:
We hypothesized that epigenetic mechanisms are responsible for the changes observed in microglia gene expression with aging, and that by definition these changes are reversible.

Methods:
We utilized a model of heterochronic parabiosis in which young (2-3-month) and aged (18-20-month) male C57Bl/6 mice (Charles River, NIA) were surgically attached and share a common blood supply. Pairs were attached for 8 weeks. Young and aged isochronic pairs served as surgical controls. Brains were collected for immunohistochemical (IHC), Western blot, and multiplex cytokine analysis. P0.5-P3 neonatal pups were used for
in vitro
culture of primary microglia and were stimulated with lipopolysaccharide (LPS) and interferon-γ for 24hr.

Results:
We screened 10 histone modifications and found that aging causes an imbalance in the epigenetic status of the CNS, with 1.26±0.08-fold higher histone H3 lysine 27 trimethylation (H3K27me3) and 0.649±0.063-fold reduced H3K27me1 (n=3, p<0.05). Pro-inflammatory stimulation of primary microglia resulted in elevated H3K27me3 (n=3, p<0.01), suggesting this mark is central to the pro-inflammatory status of aged microglia. Heterochronic parabiosis reversed these age-related changes, with reduced H3K27me3 in the brains of aged heterochronic mice (rejuvenation) and reduced H3K27me1 in young heterochronic mice (accelerated aging) (n=3-4, p<0.05).

Conclusion:
We conclude that the aged CNS has an imbalanced epigenetic landscape, and that this is reversible.
Abstract WP134: Decreased Flow Velocities After General Anesthesia Before Carotid Endarterctomy Are Not Associated with Cerebral Hyperperfusion Syndrome or Perioperative Cerebral Infarction
Authors: LIU YUMEI , Hua Yang , Jiao Liqun , Liu Beibei , Li Jingzhi , Zhou Yinghua , Zhang Nan , Feng Wuwei , Ovbiagele Bruce
Published: June 2021

Introduction:
Cerebral Hyperperfusion Syndrome (CHS) is a life threatening complication in about 3% of patients following carotid endarterectomy (CEA). There is a concern that baseline flow velocities typically decrease after general anesthesia (GA) may predispose patients to CHS and other perioperative adverse events.

Hypothesis:
Patients with decreased flow velocity after GA are at increased risk for CHS using ultrasonographic and clinical diagnostic criteria.

Methods:
We retrospectively evaluated 920 patients who received CEA from 2006 to 2016 at a major hospital in China. Middle cerebral artery blood flow velocities were measured when patients were awake and after induction of the GA. Ultrasonographic diagnostic criterion of CHS was “100% increase in flow velocity by TCD from the baseline to post-CEA”. Patients were classified into two groups: NORMAL group if flow velocity decreased <30% and LOW group if decreased >=30%. The occurrences of CHS by ultrasonongraphic and clinical criteria, perioperative cerebral infarction were compared using Chi-square test.

Results:
399 (43.4%) were classified as LOW and 522 (56.7%) patients as NORMAL. In the LOW group, there were more patients with diabetes, less patients with ICA severe stenosis and opening of anterior/posterior communicating artery. Occurrence of CHS per ultrasonographic criteria was higher in the LOW group (21.3% vs. 15.7%, P=0.03), but similar for clinical CHS criteria group (3.2%, vs 2.1%, p=0.28) and for frequency of perioperative cerebral infarction (5.8% vs.5.0%, p=0.60).

Conclusion:
Although patients with decreased flow velocities post-GA were more likely to meet ultrasonographic criteria for CHS, there were no differences in clinical CHS criteria. Our results suggest decreased flow velocities post-GA may not associated with incidence of CHS.
Abstract WP145: Presence of Vasa Vasorum Neovascularization on Optical Frequency Domain Imaging Predicts Progression of Carotid Artery Stenosis
Authors: Miura Masatomo , Yamada Kiyofumi , Kanamaru Takuya , Uchida Kazutaka , Shirakawa Manabu , Yoshimura Shinichi
Published: June 2021

Background:
Vasa vasorum neovascularization (VVN) is one of the characteristics of vulnerable plaque. The purpose of this study was to assess VVN using optical frequency domain imaging (OFDI) between symptomatic and asymptomatic carotid artery plaques, and to know its association with progression of stenosis.

Methods:
The carotid artery plaques were examined before angioplasty using OFDI system (LUNAWAVE
TM
, Terumo). VVN was defined as a no-signal tubuloluminal structures recognized on at least 3 consecutive images. A total number of VVN was compared between symptomatic and asymptomatic plaques. The stenosis was evaluated by carotid duplex scan within one year. The lesion was diagnosed as ‘progressive’ when the stenotic degree and peak systolic velocity were increased.

Results:
A total of 60 patients (29 symptomatic, 11 progression) were included. VVN was detected in 54 patients (90%), the total number of VVN was significantly higher in progressive stenosis (8.9 ± 5.7 vs. 4.5 ± 3.8,
p
= 0.02). However, there was no relationship between the number of VVN and ischemic symptom.

Conclusions:
VVN was more frequently observed in progressive stenosis. Evaluation of VVN using OFDI might be useful to predict progression of carotid artery stenosis.
Abstract WP15: Influence of Blood Pressure Parameters within 24-hours of Thrombectomy on Hospital Discharge Outcome
Authors: Mistry Eva A , Mistry Akshitkumar M , Nakawah Mohammad O , Volpi John
Published: June 2021

Background:
Presently, no evidence exists that blood pressure parameters (BPPs) in the first 24-hours after thrombectomy (T24hrs) independently predicts outcome. We aimed to study an association between discharge outcome and BPPs in T24hrs for both successful and unsuccessful thrombectomies, defined as Thrombolysis in Cerebral Infarction (TICI) score ≥ 2b and ≤ 2a, respectively.

Methods:
We retrospectively identified 54 patients at a single institution who underwent thrombectomy for emergent occlusion of anterior cerebral circulation (ICA, A1, M1, M2) from May 2015 to June 2016. We excluded patients with cancer or major cardiovascular surgeries. Primary outcome was hospital discharge: home or rehab (favorable) versus long term acute care facility or death (unfavorable). We determined if highest, lowest, average, and range of systolic (SBP), diastolic (DBP), and mean arterial (MAP) pressures were associated with outcome, utilizing univariate and multivariate logistic regression considering the following variables: age, sex, NIH-stroke scale, history of hypertension, hyperlipidemia, diabetes, smoking, atrial fibrillation, use of anticoagulative or antiplatelet medications prior to admission, administration of tPA, and the use of antihypertensive or pressor drip in T24hrs.

Results:
In patients with TICI ≥ 2b (n=43), highest SBP (odds ratio=1.04, p=0.01), highest MAP (1.05, p=0.03), SBP range (1.04, p=0.005), and MAP range (1.05, p=0.03) correlated with poor outcome. In multivariate analysis, only the SBP range trended with outcome (1.34, p=0.09). In patients with TICI ≤ 2a (n=11), BPPs did not correlate with outcome.

Conclusion:
Large variability in SBP in T24hrs after successful thrombectomies (TICI ≥ 2b) trended with poor outcome. Further studies are warranted to elucidate BPPs in T24hrs as predictors of hospital discharge.
Abstract WP151: Genetic Variant
RNF213
in non-MMD Intracranial Major Artery Stenosis/Occlusion in Chinese Han Population and HR-MRI Findings
Authors: Xue Sufang , Cheng Weiyang , Wang Wanqian , Song Haiqing , Feng Wuwei(Wayne) , Ovbiagele Brace
Published: June 2021

Introduction:
Ring finger protein 213 (RNF213) gene R4810K variant,a susceptibility locus for moyamoya disease disease (MMD) in eastern Asian, has also recently been identified as a susceptibility locus for non-MMD Intracranial Major Artery Stenosis/Occlusion (non-MMD ICASO). Due to genetic heterogeneity, further studies are needed to verify whether the R4810K variant of RNF213 is associated with ICASO in other populations.

Methods:
RNF213 gene R4810K variant was genotyped in 114 patients with non-MMD ICASO (male, 78.9%) and 268 healthy controls(male, 73.5%)from the Chinese Han population. Association between RNF213 gene R4810K variant and non-MMD ICASO was analyzed in a case-control study. Patients with RNF213 variant-related ICASO were scanned High resolution (HR)-MRI, and the presumptive diagnosis of these patients was made based on the HR-MRI characteristics.

Results:
The RNF213 R4810K variant was observed in 8 (7.0%, including 5 females) patients with non-MMD ICASO and only in 1 (0.4%) healthy control. The RNF213 R4810K variant was associated with non-MMD ICASO and increased the risk for non-MMD ICASO (P<0.01; OR, 20.2; 95% confidence interval, 2.5-163.1) (Figure 1A). Presumptive MMD based on HR-MRI findings was diagnosed in all female patients with RNF213 variant-related ICASO. However, presumptive intracranial atherosclerotic stenosis was diagnosed based on HR-MRI findings in one of three males harboring the RNF213 variant (Figure 1B).

Conclusions:
RNF213 R4810K appears to be a genetic risk variant for non-MMD ICASO among the Chinese Han population. HR-MRI supported that RNF213 variant-related ICASO should be identified as MMD in female patients. However, a similar relationship could not be established among male patients. Our data suggest that detection of R4810K in female patients with ICASO is a useful biomarker to differentiate MMD from other ICASO.
Abstract WP152: Collateral Circulation Alters Downstream Hemodynamic Stress Caused by Intracranial Atherosclerotic Stenosis
Authors: Liu Xin , Pu Yuehua , Miao Zhongrong , Wang Yilong , Liu Liping , Wang Yongjun
Published: June 2021

Background and purpose:
Fractional flow reserve (FFR) has exceled the degree of stenosis and become the new guiding post for identifying functionally severe coronary artery lesions. In the current study, we utilized a similar indicator, fractional flow (FF), to gauge the hemodynamic impact of symptomatic intracranial atherosclerotic stenosis (ICAS), and to clarify its relationships with the severity of stenosis and collateral status.

Methods:
Patients with symptomatic ICAS (70-99% stenosis) confirmed on digital subtraction angiography (DSA) were consecutively recruited. FF was obtained during DSA examination, defined as the ratio of pressures measured distal to an ICAS lesion (Pd) and within the aorta (Pa), by pressure sensors. Leptomeningeal collaterals was grading from zero (absent) to four (complete compensatory) based on DSA examination. The correlations between FF, anatomical stenosis and collateral status were analyzed.

Results:
Twenty five patients with a mean age of 55.6years were included. The median percentage of stenosis and median FF were 82.3% and 0.68, respectively. Eleven patients were evaluated as poor collaterals (grade 0-2), and fourteen patients were good collaterals (grade 3-4). Overall, the hemodynamic impact of the lesions aggravated (with a decreased FF) as the percentage of stenosis increased (r= -0.398,P =0.06). However, the collateral status significantly altered such correlation, which was more significant in patients with poor collateral circulation (r=-0.677, P=0.032), but did not exist in patients with good collateral circulation (r=-0.279, P=0.356).

Conclusions:
An anatomically severe (70-99%) symptomatic ICAS lesion may lay significant hemodynamic stress downstream as assessed by the indicator FF. However, a good collateral circulation may mitigate such hemodynamic impact, which may partly explain the protective effect of good collaterals against recurrent stroke in such patients.
Abstract WP163: Post-stroke Aphasia Severity is Determined by the Disorganization of Residual White Matter Networks
Authors: Marebwa Barbara K , Fridriksson Julius , Yourganov Grigori , Feenaughty Lynda , Rorden Chris , Bonilha Leonardo
Published: June 2021

Introduction:
Many stroke survivors who suffer from aphasia in the acute period experience spontaneous recovery within the first six months post-stroke. About 20% sustain permanent and disabling language problems and the factors that drive incomplete recovery are not clear. Cortical dysfunction may occur in areas seemingly spared by the stroke due to changes to metabolism as well as loss of white matter connectivity and disruption of cortical and subcortical network integrity. We hypothesized that residual white matter connectivity could provide a personalized predictor of the severity of chronic aphasia.

Methods:
We reconstructed the individual structural whole-brain connectome from 90 right handed participants with a single left hemisphere ischemic or hemorrhagic stroke. All participants underwent language assessment using the Western Aphasia Battery (WAB-AQ). Data analysis was performed on each subject’s individual connectome, a weighted adjacency matrix
M
of size 189 x 189. We measured comprehensive white matter topological network organization using Newman’s modularity algorithm and calculated the probability of brain regions clustering together though a community affiliation index, which was used to determine the structural fragmentation of white matter networks in the left hemisphere relative to right hemisphere, expressed by a fragmentation index.

Results:
Patients with greater post-stroke left hemisphere network fragmentation and higher modularity index had more severe chronic aphasia, controlling for the size of the stroke lesion. Modularity and fragmentation index significantly increased with aphasia severity (r = -0.42), and (r = -0.43) respectively. Even when the left hemisphere was relatively spared, patients with disorganized community structure had significantly worse aphasia.

Conclusion:
Our findings confirm that residual white matter integrity and disorganization of neuronal networks are important determinants of chronic aphasia severity. Furthermore, the assessment of residual connectome white matter organization through modularity provides a comprehensive and personalized measurement that may be used as a marker for clinical staging and aphasia treatment planning.
Abstract WP165: Mexican Americans Receive Less Intensive Stroke Rehabilitation Than non Hispanic Whites
Authors: Morgenstern Lewis B , Sais Emma , Fuentes Michael , Ifejika Nneka , Jiang Xiaqing , Horn Susan , Lisabeth Lynda
Published: June 2021

Background:
Mexican Americans (MAs) have worse neurologic, functional and cognitive outcomes after stroke than non Hispanic whites (NHWs). Stroke rehabilitation is important for outcome. In a population-based study, we sought to determine if allocation of stroke rehabilitation services differed by ethnicity.

Methods:
Consecutive stroke patients were identified for a three month time period as part of the Brain Attack Surveillance in Corpus Christi (BASIC) project, Texas, USA. Cases were validated by physicians using source documentation. Patients were followed prospectively for three months following stroke to determine self-reported rehabilitation services. Descriptive statistics were used to describe the study population. Ethnic comparisons of rehabilitation services were made using chi-squared or Fisher’s exact tests.

Results:
Seventy-two subjects (50 MA, 22 NHW) were followed. Mean age, NHW-69 (sd-13), MA-66 (sd-11) years, sex (NHW 55% male, MA 50% male) and median presenting NIHSS (NHW-2.5, MA-3.0) did not differ significantly. There were no ethnic differences in the proportion of patients who were discharged home without rehabilitation services (p=0.9). Among those who received rehabilitation (n=48), the figure shows the distribution of the first place for services. NHWs were more likely to be discharged to inpatient rehabilitation (73%) compared with MAs (30%), p=0.016. MAs (51%) were much more likely to be receive home rehabilitation services compared with NHWs (0%) (p=0.0017).

Conclusions:
In this population-based study, MAs were more likely to receive home-based rehabilitation while NHWs more likely to get inpatient rehabilitation. This disparity may, in part, explain the worse stroke outcome in MAs.
Abstract WP166: Dietary Nitrate Supplements and Ischemic Stroke Recovery: A Pilot Study
Authors: Bushnell Cheryl , Beavers Daniel , Miller Gary , Reeves Susan , Duncan Pamela , Basu Swati , Kim-Shapiro Daniel
Published: June 2021

Introduction:
Dietary nitrate improves cerebral blood flow and enhances physical performance by improving exercise capacity. We designed a proof-of-concept study to show increases in plasma nitrate and nitrite levels in ischemic stroke patients treated with beetroot juice shots vs placebo juice (nitrate removed). We assessed gait speed after 30 days and safety/adverse events with both groups.

Methods:
In a randomized placebo-controlled double-blind design, patients with NIHSS of ≥ 2 but < 20, with fair or good sitting balance and score >0 on hip flexion on the short Fugl-Meyer, within 5 days of stroke onset were enrolled. Those treated with IV alteplase or endovascular therapy, gait speed > 0.8 cm/sec, or taking nitrate-containing medications were excluded. After consent, patients were randomized to beetroot vs placebo juice. On days 1 and 30, blood was drawn for nitrate and nitrite levels before and one hour after drinking 70 cc (3.8 mM nitrate) beetroot juice (James White Fruit Juices) or an identically-appearing placebo juice, plus vitamin C 500 mg daily for 30 days in each group. On day 30, gait speed (using the 4 m walk) was assessed.

Results:
Eighteen participants (6 women, 12 men, 12 white, 4 African American and 2 other race-ethnicities, median age 64.6 IQR (58.7, 70.0)) were consented, 17 completed treatment (1 terminated treatment because of nausea), 16 followed for 30 days and 13 for 90 days. Baseline characteristics were balanced with regard to admission NIHSS (median 5.0 in each group), age, sex, race, risk factors, baseline gait speed (median 0.17 m/sec in active and 0.13 m/sec in placebo), and baseline nitrate/nitrite levels. There was no difference in adverse events in the two groups. The mean treatment-specific changes in nitrate were 236 micromoles/L (95% CI 170, 302) in the active and 0 (95% CI -64, 64) in the placebo group (p<0.0001). For nitrite, active group increased by 313 nanomoles/L (37, 588) and 20 nanomoles for placebo (-211, 252); p=0.045. Gait speed increased by 0.26m/sec in the active and 0.30m/sec in placebo group.

Conclusions:
Beetroot juice was associated with an increase in nitrate and nitrite levels, but was not associated with a change in gait speed after 30 days. Further studies with a larger population of stroke patients may be warranted.
Abstract WP179: Rate of Pulmonary Embolism After Cerebral Venous Thrombosis
Authors: Liberman Ava L , Merkler Alexander E , Gialdini Gino , Lerario Michael P , Messe Steven R , Kamel Hooman
Published: June 2021

Introduction:
Cerebral vein thrombosis (CVT) is associated with an increased risk of subsequent venous thromboembolism. It is unknown whether the risk of pulmonary embolism (PE) after CVT is similar to that of PE after deep venous thrombosis (DVT).

Methods:
We performed a retrospective cohort study using administrative claims data from all emergency department visits and hospitalizations in California from 2005-2011, New York from 2006-2013, and Florida from 2005-2013. We identified patients with CVT or DVT as well as the primary outcome of PE using previously validated
International Classification of Diseases, Ninth Revision, Clinical Modification
(
ICD-9-CM
) codes. In order to minimize misclassification error, patients with both CVT and DVT during the same index hospitalization were excluded and patients with CVT were censored at the time of development of DVT and vice versa. Kaplan-Meier survival statistics and Cox proportional hazards models were used to compare the risk of PE after CVT versus after DVT while adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index.

Results:
We identified 4,450 patients with CVT and 217,589 patients with DVT. During a mean follow-up of 2.0 (±1.7) years, 124 patients with DVT developed a PE and 18,698 patients with DVT developed a PE. Patients with CVT were younger (mean age 45 vs 63), more often female (71% vs 52%), more often pregnant, and had fewer vascular risk factors than patients with DVT. During the index hospitalization, the rate of PE was 1.5% (95% confidence interval [CI], 1.1-1.8%) in patients with CVT and 6.2% (95% CI, 6.1-6.3%, p<0.001) in patients with DVT. By 5 years, the cumulative rate of PE after CVT was 3.7% (95% CI, 3.0-4.4%) compared to 10.5% (95% CI, 10.3-10.6%, p<0.001) after DVT. After adjustment for demographics and comorbidities, CVT was associated with a significantly lower hazard of PE when compared to DVT (hazard ratio, 0.31; 95% CI, 0.26-0.38).

Conclusion:
In a large, heterogeneous population, we found that the risk of PE after CVT was significantly lower than that of PE after DVT. Among patients with CVT, the greatest risk for PE was apparent during the index hospitalization.
Abstract WP18: Cerebral Mechanical Thrombectomy Simulator Using Hydrogel Polymers and 3D Printing Technology
Authors: Campbell Timothy , Stone Jonathan , Parmar Arun , Vates Edward , Miranpuri Amrendra
Published: June 2021

Introduction:
While stroke remains a leading cause of death and disability, recent advances in endovascular technology an important opportunity to make a significant impact in clinical outcomes. However, training opportunities are rare, preventing dissemination of these techniques. Hands-on training is further complicated by the critical time to therapy associated with stroke treatment. This physical simulator was built for neurosurgical residents and fellows to practice mechanical thrombectomy.

Methods:
A simplified virtual model of the anterior cerebral circulation was created based on patient imaging. This luminal model was 3D printed using flexible filament and attached to a guide catheter at the proximal carotid to provide endovascular access and an IV tube at the distal M2 branches to permit outflow. A 7Fr sheath was also connected at the anterior cerebral artery to permit placement of a simulated clot model and simulate a proximal M1 occlusion. This entire construct was placed into a container of polyvinyl alcohol (PVA) and after crosslinking the flexible print was removed.

Results:
Using 3D printing technology and polymer hydrogels, a low-cost, high fidelity stroke model was achieved. Despite its simplified anatomy, the model permitted realistic wire and catheter navigation through the different segments of the internal carotid and middle cerebral arteries. The ACOM sheath provided a convenient method to reliably place an embolism and created a life-like proximal M1 occlusion. Recanalization was performed using the solumbra technique, which is used in live-patient cases.

Conclusions:
This model demonstrated proof of concept for a mechanical thrombectomy simulation. The angiographic profile and response to endovascular tools created a training experience similar to live endovascular procedures. As the model is perfected visually and mechanically, next steps are to perform validation studies and create a training curriculum.
Abstract WP180: Rural-Urban Differences in Stroke Incidence, Mortality and Risk Factor Prevalence in Ontario
Authors: Jeyakumar Geerthana , Tu Jack V , Austin Peter C , Hall Ruth , Jin Albert , Manuel Doug , Silver Frank L , Swartz Rick , Chu Anna , Khan Anam M , Kapral Moira K
Published: June 2021

Introduction:
Little is known about stroke incidence, mortality and risk factor prevalence in rural versus urban regions. We used linked population-based administrative databases to compare cardiovascular risk factors, stroke incidence and stroke-related death in residents of rural and urban Ontario, Canada.

Methods:
We used a sub-population of the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) cohort, consisting of individuals aged 40 to 105 in Ontario with no known hospitalization for stroke in the 20 years prior to January 1, 2008. We defined rural regions as those with a population size ≤ 30, 000. We compared the age- and sex- standardized prevalence of risk factors, as well as 5-year stroke incidence and stroke-related mortality rates, in people residing in rural versus urban areas.

Results:
The study sample consisted of 6,207,032 individuals. Compared to residents of urban regions, rural residents were more likely to smoke (25.3% versus 19.3%), be obese (25.1% versus 19.3%) and live in a low-income area (43.5% versus 38.3%) (P<0.001 for all comparisons). However, there were no differences in the proportion of residents with hypertension, diabetes and atrial fibrillation. Age- and sex-standardized stroke incidence was higher in rural compared to urban areas (2.18 versus 1.99 events/1000 person-years; p<0.001), as was stroke-related mortality (0.79 versus 0.65 events/1000 person-years; p<0.001).

Conclusions:
Certain cardiovascular risk factors have increased prevalence in rural areas compared to urban areas. Furthermore, stroke incidence and mortality rates were greater in rural areas in Ontario. Future efforts should focus on reducing regional discrepancies in social determinants of health and addressing risk factor prevalence, particularly smoking and obesity, in rural regions.
Abstract WP181: Timing of Percutaneous Endoscopic Gastrostomy (PEG) for Acute Ischemic Stroke Inpatients in the United States
Authors: Albert George P , George Benjamin P , Kelly Adam G , Hwang David Y , Holloway Robert G
Published: June 2021

Background and Purpose:
Stroke guidelines recommend time-limited trials of nasogastric feeding prior to placement of percutaneous endoscopic gastrostomy (PEG) tubes. We sought to describe timing of PEG placement and identify factors associated with early PEG for acute ischemic stroke.

Methods:
We designed a retrospective observational study to examine time to PEG for ischemic stroke admissions in the Nationwide Inpatient Sample, 2001-2011. We defined early PEG placement as 1-7 days from admission. Using multivariable regression analysis, we identified the effects of patient and hospital characteristics on time to PEG.

Results:
We identified 34,623 admissions receiving a PEG from 2001-2011, 53% of which received the PEG early. Among hospitals placing ≥10 PEG tubes, median time to PEG for individual hospitals ranged from 3 days to over 3 weeks (interquartile range: 6-8.5 days). Older adult age groups were associated with early PEG placement (≥85 years vs. 18-54 years: Adjusted Odds Ratio [AOR] 1.68, 95% CI 1.50-1.87). Those receiving a PEG tube and tracheostomy were less likely to receive the PEG early (vs. no tracheostomy; AOR 0.27, 95% CI 0.24-0.29), and these patients were more often younger compared to PEG only recipients (
Figure
). Those admitted to high volume hospitals were more likely to receive their PEG early (≥350 vs. <150 hospitalizations; AOR 1.26, 95% CI 1.17-1.35).

Conclusions:
More than half of PEG recipients received their surgical feeding tube within 7 days of admission. The oldest old, who may be the most likely to benefit from time-limited trials of nasogastric feeding, were most likely to receive a PEG early.