bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 24: Helping to Educate Women About the Risk of Stroke (HER-Stroke): Initial Results from a Teaching Intervention
Authors: Dirickson Amanda , Stutzman Sonja , Beal Claudia , Novakovic Roberta , Stowe Ann , Martinez Maria , Flaherty James P , Goldberg Mark P , Alberts Mark J , Olson Daiwai M
Published: June 2021

Introduction:
Recent studies reveal deficiencies in educating women about stroke. The vast majority of stroke education is presented as gender neutral or with a male bias. This study examined if a computer-based, gender-specific education program (HER-Stroke) increased women’s awareness of stroke signs and symptoms.

Methods:
This 2-phase prospective study with 2-week follow-up examined gender-specific education based on Knowles’ Theory, enrolled 225 women with at least one stroke risk factor from any inpatient setting or neurology outpatient setting. Phase I, 75 women received standard stroke education (Group A). Phase II, 150 women randomized to standard (Group B) vs HER-Stroke education (Group C). Knowledge is scored as the percent of questions answered correctly; confidence is the percent of questions attempted; and accuracy is percent correct of those attempted.

Results:
Mean age was similar for Group A, B, C (54.4, 57.9, 52.5 years) respectively. There were no statistically significant differences in mean knowledge scores comparing groups A B and C: (69.4%, 71.6%, 69.0%; p=0.67), mean confidence scores for groups A, B, and C respectively (80.8%, 83.2%, 80.2%; p=0.77), or mean accuracy scores for group A B and C (86.2%, 85.6%, 85.0%; p=0.75). Regression analysis revealed that older age was associated with lower knowledge scores (p<.001) and lower confidence scores (p<.001). After controlling for age, the intervention was associated with a statistically significant difference in knowledge and confidence (p<.001).

Conclusions:
Enhanced efficacy among younger participants may reflect experience and comfort using technology. While the intervention was not associated with a change in overall scores, after controlling for age there was a statistically significant difference among groups. Further research including unmeasured covariates is needed to explore optimal stroke education formats for older learners.
Abstract 25: Mild Cognitive Impairment the New Risk Factor for Stroke?
Authors: Gaillard Trudy , Miller Elaine T , Sampsel Debi , Bakas Tamilyn
Published: June 2021

Background and Purpose:
Hypertension, prediabetes and type 2 diabetes are major risk factors for stroke, particularly among elderly African Americans (AAs). However, whether there are racial differences in the characteristics of patients with mild cognitive impairment (MCI) are unknown. The purpose of this study is to explore racial differences in MCI, blood pressure and glucose levels among older AAs and White Americans (WAs).

Methods:
We recruited 79 free living older adults (>65 years) (40 AAs and 39 WAs). Cognitive impairment was measured using the Montreal Cognitive Assessment (MoCA). We defined MCI as MoCA score between 18-26. In addition, systolic and diastolic blood pressure and hemoglobin A1C (A1C) were obtained in each participant.

Results:
The mean age of our group was 71.4±5.0 years and body mass index 29.1±5.9 kg/m
2
. The AAs were younger than WAs (70.3±5.1 vs. 72.4±4.7 years, p=0.06), there were no difference in body mass index (29.1±5.9 vs 27.7±5.4kg/m
2
, p=0.26). We found racial differences in MCI between our AA and WA participants. The AAs in our group had significantly lower MoCA scores compared to WAs (21±4.3 vs 25.5±3.2, p=0.0004). In addition, the systolic blood pressure (137.4±17.1 vs.128.25±14.9 mmHg, p=0.01) and diastolic blood pressure (77.3±10.8 vs.72.9±9 mmHg, p=0.05) were statistically higher in our AAs compared to WAs. Finally, the A1C was statistically higher in our AA vs. WA participants (5.8±0.4 vs. 5.5±0.29%, p=0.001).

Conclusions:
Our pilot data clearly demonstrates racial differences in MCI. Our study confirms that AAs with MCI are younger, have higher blood pressure and A1C levels when compared to WAs. Therefore, future studies are warranted to determine whether treatment of blood pressure and dysglycemia can reverse MCI in older AAs.
Abstract 28: Virginia Stroke Coordinators Successfully Collaborate to Improve Door to Needle Times and EMS Relationships
Authors: Turner Heather , Stevens Stacie , McGhee Tiffany , Doherty Donna , Lane Patricia
Published: June 2021

Background and Issues:
The Virginia Stroke Coordinators Consortium (VSCC) was founded in 2009 with a stated goal of striving for high-level evidence based stroke care for all Virginians.

Purpose:
In CY2015, the VSCC set two specific goals, to improve arrival to IV TPA administration (“Door to Needle”-DTN) times in Virginia and to improve our stroke team relationships with EMS.

DTN Time Methods:
We shared the Target Stroke Phase 2information and best practices, we regularly shared our own best practices at our monthly meetings (one live meeting per quarter) through formal presentations and informal discussion, we reviewed current journal publications related to decreasing DTN times and we shared information about and encouraged participation in nationally offered webinars on improving arrival to CT and DTN times.

DTN Time Results:
29 of the 60 hospitals represented within the VSCC participate in Get with the Guidelines so we used that data as a sample of our work. To measure our success, we compared CY2014 Target Stroke Honor Roll reports to CY2015 for the state of Virginia and saw improvement (beyond the level of improvement seen at the national level) in every measure including percent of ischemic strokes that received thrombolysis, percent of patients with a DTN time of 60m or less and percent of patients with a DTN time of 45m or less (including and excluding patients with documented reasons for delay.)

EMS Methods:
Again, shared Target Stroke and our own best practices, shared EMS feedback methods and standardized feedback forms, included EMS in our meetings and presentations, encouraged communication with local EMS providers, worked with state wide EMS to develop template for post TPA transport.

EMS Results:
The VSCC was surveyed in April of 2014(n-34) and again in April 2015(n-31). We saw that the number of coordinators interacting with EMS increased to 100% of respondents, frequency of EMS interaction increased, those with monthly interaction doubled, EMS feedback increased and 48% of respondents felt their relationships with EMS had improved. (43% already felt they had a good relationship.)

Conclusion:
Working together, Stroke Coordinators can significantly lower door to IV TPA times and improve stroke team relationships with EMS throughout the state.
Abstract 3: Stent Placement versus Best Medical Therapy for Symptomatic Intracranial Stenosis. A Meta-analysis of Randomized and Non-randomized Studies
Authors: Ishfaq Muhammad F , Aytac Emrah , Afgan Sher , Qureshi Adnan I
Published: June 2021

Objective:
There is controversy regarding the role of stent placement for the treatment of symptomatic intracranial stenosis. Several small trials have inconclusively compared the efficacy of stent placement with medical therapy in patients with symptomatic intracranial stenosis. We therefore conducted a meta-analysis to evaluate the clinical efficacy and safety of intracranial stent placement relative to best medical therapy in patients with symptomatic intracranial stenosis.

Methods:
We assessed risk of bias and overall quality of the included trials. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using random-effects models. Study end points were the proportion of subjects who had ischemic stroke, any stroke and transient ischemic stroke in qualifying artery. The safety end points were the proportion of subjects who had symptomatic intracerebral hemorrhage (sICH) and mortality.

Results:
A total of 1029 patients were analyzed of whom 453 were treated with intracranial stent placement in three randomized trials and three non randomized studies . sICH was significantly higher in patients who underwent intracranial stent placement (OR 5.85, 95% CI 1.86-18.34, P= .002) than among those who received medical therapy. Stroke in qualifying artery during follow-up was also significantly higher in subjects who underwent intracranial stent placement than among those who received medical therapy (OR 2.08, 95%CI 1.31-3.32, P= .002). There was no difference in mortality and transient ischemic stroke in qualifying artery among subjects who received intracranial stent compared with those who received medical therapy, (OR 0.83, 95%CI 0.38-1.83, P= .65 & OR 0.78, 95%CI 0.29-2.11, P= .63), respectively.

Conclusion:
Modification in techniques of intracranial stent placement are required to reduce the rates of sICH and stroke in qualifying artery to provide benefit over best medical treatment.
Abstract 34: A Decrease in Blood Pressure is Associated with Unfavorable Outcome in Patients Undergoing Thrombectomy Under General Anesthesia in the Mr Clean Study
Authors: Treurniet Kilian M , Berkhemer Olvert A , Ward-van der Stam Vivian M , Lingsma Hester F , Hollmann Marcus W , Vuyk Jaap , van Zwam Wim H , van der Lugt Aad , van Oostenbrugge Robert J , Dippel Diederik W , Roos Yvo B , Marquering Henk A , Majoie Charles B ,   for the MRCLEAN investigators
Published: June 2021

Background:
Patients treated with thrombectomy for acute ischemic stroke (AIS) under general anesthesia (GA) appear to have less favorable outcomes than patients treated under local anesthesia. Anesthetics used for the induction of GA are known to be associated with decreases in blood pressure. The aim of this study was to determine whether a fall in blood pressure during treatment under GA affects functional outcome.

Methods:
This subgroup analysis included Patients from the MR CLEAN trial treated with endovascular therapy under GA. The investigated variables were the difference between baseline mean arterial pressure (MAP) and mean MAP during intervention as well as the difference between baseline MAP and the lowest MAP during intervention. Their association with a shift in the outcome on the score on the modified Rankin Scale (mRS) at 90 days from onset was determined using ordinal logistic regression with adjustment for prognostic baseline variables.

Results:
Sixty of the 85 patients treated with GA in MRCLEAN had sufficient anesthetic information available and were included in this analysis. The difference between baseline MAP and mean MAP during intervention was associated with decreased likelihood of favorable outcome on the mRS (adjusted common odds ratio (acOR) 0.95 per point mmHg,
95%CI 0.92-0.99
)
.
For a mean MAP during intervention 10 mmHg lower than baseline MAP this would constitute an odds of favorable outcome (
1/(0.95^10)=
) 1.67 times lower than patients without this decrease. The association with outcome of the difference between baseline MAP and the lowest MAP during intervention was not significant (acOR 0.97 per point mmHg,
95%CI 0.94-1.00, p=0.09).

Conclusion:
A decreased MAP during thrombectomy under GA as compared to baseline MAP is associated with a lower likelihood of favorable outcome. This finding underlines the importance of blood pressure management during mechanical thrombectomy under GA.
Abstract 35: MR CLEAN Registry: A Post-trial Multicenter Registry of Intra-arterial Treatment for Acute Ischemic Stroke in the Netherlands
Authors: Jansen Ivo , Mulder Maxim , Goldhoorn Robert-Jan , van der Lugt Aad , Marquering Henk , van Zwam Wim , Roos Yvo , Vos Jan-Albert , Slump Cornelis , Schonewille Wouter , Boiten Jelis , Lyclama a Nijeholt Geert , Martens Jasper , Hofmeijer Jeanette , van Oostenbrugge Robert , Dippel Diederik , Majoie Charles
Published: June 2021

Background & Purpose:
Intra-arterial therapy (IAT) is being implemented worldwide as the main treatment option for acute ischemic stroke (AIS). We wondered whether effectiveness and safety results that have been reported in randomized clinical trials can be reproduced in everyday clinical practice. We will report results of the Dutch National post MR CLEAN IAT registry including work flow parameters, primary and secondary outcomes, as well as serious adverse events.

Methods:
The MR CLEAN Registry is a prospective registry of all patients undergoing IAT for AIS in the Netherlands, started after completion of the MR CLEAN trial in March 2014. Registration was required for reimbursement. A core set was defined, with inclusion criteria similar to those of the MR CLEAN trial, including a proven anterior circulation occlusion and treatment possible withing 6 hours from onset. The primary study outcome is the score on the modified Rankin Scale (mRS) at 90 days. The secondary clinical outcome is NIHSS after 24 to 48 hours. Secondary radiological outcomes include the mTICI score on DSA and final infarct volume and major bleeding on follow up NCCT. We used a propensity weighted and an unadjusted ordinal logistic regression model to compare outcomes in the MR CLEAN Registry core and total dataset with the treatment arm of MR CLEAN.

Results:
Between March 2014 and August 2016 the inclusion rate of the MR CLEAN Registry has been increasing steadily to an average of 79 (SD 22) per month for a cumulative inclusion of 1548 patients in July 2016 (Figure 1).

Conclusions:
The MR CLEAN registry data is now being analyzed. Results will be reported at the conference.
Abstract 40: The Disappearing Core: Time to Re-think Irreversible Injury in This Era of Endovascular Therapy
Authors: Hsia Amie W , Luby Marie , Armonda Rocco , Liu Ai-hsi , Benson Richard T , Leigh Richard , Lynch John K , Nadareishvili Zurab , Latour Lawrence L
Published: June 2021

Background and Purpose:
Early and complete recanalization achieved in this new era of endovascular therapy (ET) can result in nearly imperceptible lesions on post-treatment MRI. In this context we have observed a pattern of lesion evolution on MRI that is atypical from that seen following IV tPA alone, including striking reversal of the ischemic core. We sought to determine the frequency of acute lesion reversal following ET, and its association with sustained reversal and clinical outcome.

Methods:
Patients were included in this study if: 1) ET for anterior territory ischemic stroke from Jan 2015 to July 2016, 2) baseline pre-ET and 24h MRI, and 3) consent for research. Two raters evaluated ADC maps for early “reversal” (defined visually as >50%) by comparing 24h to baseline. FLAIR MRI at 30d were later assessed for reversal from baseline, blinded to 24h scan. Early neurological improvement (ENI) was defined as decrease in NIHSS≥8 at 24h. Good clinical outcome defined as mRS≤2.

Results:
Twenty-two patients were included: median age 68.5 years, 73% women, median baseline NIHSS 19. Median time from last known well to recanalization 254 min. TICI 2b/3 in 91%. ADC reversal in 12 of 22 (55%) at 24h. Reversal at 30d was associated with 24hr (p=0.002) with two having no visually appreciable infarct at 30d. Baseline NIHSS did not differ for early reversal versus without (18.5 vs. 19.5), however NIHSS differed at discharge (1.5 vs. 8.5, p=0.003); early reversal is significantly associated with ENI (83% vs. 30%, p=0.027), but not with good clinical outcome at 30-90d (50% vs. 30%, p=0.415).

Conclusions:
In this new era of consistently effective ET, salvageable tissue includes not just penumbra but ischemic core, previously considered irreversibly injured. Despite lesion reversal and ENI, for some patients, independent outcome is not achieved, a finding that reinforces the need for adjunctive treatments to build upon the success of ET.

Figure:
Example of a patient with early ADC reversal.
Abstract 44: Hdac3i Alleviated Ischemic Stroke Injury Through Modulating Aim2 Inflammasome and Microglia Polarization
Authors: Zhang Meijuan , Xia Mingxu , Zhao Qiuchen , Xu Yun
Published: June 2021

Background:
Inflammasome in microglia are critical to elicit inflammatory cascades in ischemic stroke. Histone deacetylases 3 (HDAC3) regulate acetylation states of histone and non-histone proteins and could be a powerful regulator of inflammatory process in stroke.

Methods:
Primary microglia, BV2 cells subjected to oxygen glucose deprivation (OGD) or LPS stimulation were applied to mimic inflammatory response
in vitro
. Middle cerebral artery occlusion (MCAO) model were applied to mimic acute stroke
in vivo
. Ischemic infarct volume and neurological functions were evaluated through 2,3,5-triphenyltetrazolium chloride (TTC) staining and Neurological Severity Scores (NSS) respectively. Expression of HDAC3, AIM2 inflammasome were detected by western blotting, PCR. Immunofluorescence was used to detect M1/M2 polarization. Luciferase activity of absent in melanoma 2 (AIM2) reporter promoter constructs was measured by fluorospectrophotometer. AIM2 knockdown and over-expression leti-virus were constructed to decrease or increase AIM2 expression. HDAC3 inhibitor RGFP966 was used to inhibit acetylation activity of HDAC3.

Results:
HDAC3 is widely distributed in cerebral cortex, lateral ventricular , hippocampus, cerebellar cortex ; HDAC3 and AIM2 expression were enhanced in LPS stimulated-microglia and MCAO model. A marked stimulatory effect of RGFP966 on H3K9Ac was observed in nuclear extracts form BV2 cells at the dosage of 15 uM. Treatment of RGFP966 increased both IL-4-stimulated expression of Ym-1 and CD206 at 4 h, 10 h, 24 h, 48 h. AIM2, NLRP-1 and NLRP3 significantly increased in MCAO+Vehicle group compared to sham group, but decreased in MCAO+RGFP966 group. RGFP966 inhibited the elevation of circulatory IL-18 and IL-1β induced by stroke. RGFP966 decreased infracted size and alleviated neurological deficit.

Conclusions:
HDAC3i alleviated ischemic stroke injury through modulating AIM2 inflammasome and microglia polarization. Selective HDAC3 inhibitor-RGFP966 could be a potential medication for combating ischemic brain injury.
Abstract 45: IRF5/IRF4 Regulatory Axis Mediated Microglial M1/M2 Polarization After Ischemic Stroke
Authors: Mamun Abdullah A , Alegria Javiera B , Yan Xu , Louise McCullough D , Fudong Liu
Published: June 2021

Introduction:
Microglia have a prominent role in initiating, sustaining and resolving post-stroke inflammation. The pathology of stroke largely depends on the spectrum of microglial activation with the classically (M1; pro-inflammatory) and/or alternatively activated (M2; anti-inflammatory) phenotype. It has been reported that interferon regulatory factor 5 (IRF5) and IRF4 regulate the M1 and M2 phenotype of macrophages respectively in systemic inflammation; however, it is unknown if microglial activation is regulated by the same mechanism after stroke. We hypothesize that IRF5/IRF4 directs M1/M2 microglial polarization respectively after stroke and the balance of the IRF5/IRF4 regulatory axis influences stroke outcomes.

Methods:
C57BL6 mice (8-12 weeks) were subjected to a 90-minute middle cerebral artery occlusion (MCAO). Stroke outcomes were evaluated at 12h, 3d, 10d of MCAO. Protein and mRNA levels of IRF4/5 at each time point were examined by IHC, Western blot and RT-PCR. Microglial phenotypes were evaluated by flow cytometry (FC) and determined by the ratio of MHC-II
+
(M1) or CD206
+
(M2) microglia number over the total microglia. IRF4/IRF5 conditional knockout (CKO) mice will also be utilized to examine the effect of gene deletion on stroke outcomes.

Results:
IRF4 protein level increased at 10d in the ipsilateral brain lysates, but IRF5 level decreased at day 10 compared to that of 3d. M2 microglia number was higher at 10d vs. 3d by FC analysis; while M1 microglia ratio was lower at 10d vs. 3d. The Iba1
+
IRF4
+
(M2) and Iba1
+
IRF5
+
(M1) cell number by IHC showed the same pattern as that in FC data. In addition, IRF4 mRNA in FC-sorted microglia was up-regulated at 3d of stroke and peaked at 10d, but IRF5 mRNA significantly increased at 3d vs. sham and declined to baseline at 10d. IRF5-CKO mice had significantly smaller infarct volume and improved behavior deficits than IRF5
flox/flox
mice while IRF4-CKO mice had worse outcomes than that of IRF4
flox/flox
mice.

Conclusion:
IRF5-mediated pro-inflammatory phenotype (M1) is predominate in the acute stage of stroke that switches to IRF4-mediated anti-inflammatory phenotype (M2) in the chronic stage. IRF5/IRF4 regulatory axis regulates the microglial M1/M2 activation and impacts stroke outcomes.
Abstract 46: The Influence of Age and Stroke on Gut Inflammation and Microbiota
Authors: Bravo-Alegria Javiera B , Honarpisheh Pedram , Spychala Monica , McCullough Louise D , Venna Venugopal R
Published: June 2021

Introduction:
Earlier work by our laboratory and other groups has identified that aging leads to changes in both the immune system and the microbiome. The elderly have high mortality and more disability after a stroke, a finding that is recapitulated in murine model. Recently, pro-inflammatory γδ T cells have received increasing attention as a major contributor to gut immune responses. These cells may be a link in the bidirectional communication between the microbiome and the central nervous system. We hypothesize that fecal transplant of aged biome into young animals will enhance inflammation, γδ T cell numbers, and worsen functional recovery after stroke in young mice.

Methods:
Young C57BL/6 male mice, were randomized and subjected to sham surgery/right middle cerebral artery occlusion (MCAO-60min) followed by reperfusion. All mice received streptomycin treatment at 24h and 48h after MCAO. Subsequently, mice were gavaged with biome from either young or aged animals at 72 and 96 h post-stroke. Behavioral and functional outcomes were evaluated. Animals were sacrificed 15 days after stroke. Brain atrophy was quantified, and Flow Cytometry (FACS) and immunohistochemistry was performed on gut tissue and spleen to determine if stroke or the aged biome influence γδ T cells.

Results:
Young mice transplanted with aged biome take a longer time to regain their pre-stroke body weight. These mice have higher post-stroke hyperactivity compared with mice treated with young biome, as measured by average velocity (p<.006) and total distance traveled (p<.006) in the Open Field. Young mice given aged biome had poorer grip strength, as well as a depressive phenotype, when compared with mice transplanted with young biome. FACS analysis shows higher levels of γδ T cell in the gut with stroke and with fecal transplant of aged biome (sham vs. stroke p=0.0443; young vs. aged biome p=0.0199).

Conclusion:
Collectively our findings suggests that the gut microbiome plays an important role in post-stroke recovery. Understanding the underlying mechanisms may identify novel therapeutic targets for the treatment of stroke patients.
Abstract 50: Persistent Racial/Ethnic Disparities Despite Declining Rates of Ischemic Stroke Hospitalizations Among Medicare Beneficiaries, 2001-2013
Authors: Lichtman Judith H , Leifheit-Limson Erica C , Wang Yun , Rundek Tatjana , Goldstein Larry B , Waddy Salina P , Sacco Ralph L
Published: June 2021

Background:
Stroke hospitalizations in the US have declined over the last decade, but little is known about whether decreases are similar across racial/ethnic groups. We compared ischemic stroke hospitalization rates and geographic patterns across the US from 2001-2013 for elderly Hispanics, Blacks, Whites, and those of other race/ethnicity.

Methods:
Ischemic stroke hospitalizations (ICD-9 primary discharge codes 433, 434, 436) were identified among Medicare fee-for-service beneficiaries aged ≥65y in 2001-2003 and 2011-2013. National annualized rates for each period were calculated per 100,000 person-years (PY). A spatial mixed model with a Poisson link function and adjustment for age and sex was fit to calculate and map county-specific risk-standardized stroke hospitalization rates for each racial/ethnic group.

Results:
National annualized stroke hospitalization rates decreased by 15% between 2001-2003 and 2011-2013 (1298/100,000 PY to 1103/100,000 PY). County-level risk-standardized hospitalization rates varied across the US and among the four racial/ethnic groups (figure). Regardless of time period, Blacks had the highest rates, followed by Whites, Hispanics, and other races. The absolute and relative declines in risk-standardized hospitalization rates were smallest for Hispanics (173/100,000 PY; 15%) and Blacks (196/100,000 PY; 12%) compared to Whites (243/100,000 PY; 19%) and other races (273/100,000 PY; 33%).

Conclusions:
Although national hospitalization rates for ischemic stroke among those aged ≥65y decreased between 2001 and 2013, the decline varied by race/ethnicity, with persistent disparities between groups. Despite the declines in US stroke hospitalizations, these racial/ethnic differences call for greater prioritization of prevention intervention programs to reduce stroke disparities. AHA/ASA efforts to expand stroke systems of care also need to address these disparities.
Abstract 54: APOE Genotype Modifies the Effect of Blood Pressure on Long-term Clinical Deterioration Following Intracerebral Hemorrhage
Authors: Biffi Alessandro , Phuah Chia-Ling , Kourkoulis Christina , Schwab Kristin , Ayres Alison M , Gurol M. Edip , Greenberg Steven M , Viswanathan Anand , Anderson Christopher D , Rosand Jonathan
Published: June 2021

Introduction:
Intracerebral Hemorrhage (ICH) is a severe manifestation of cerebral small vessel disease, and identifies individuals at high risk for recurrent ICH, ischemic stroke, dementia, late-life depression and gait impairment. Blood pressure (BP) following ICH is strongly associated with risk of these clinical sequelae.

Hypothesis:
We sought to test whether the most potent genetic risk factors for ICH recurrence,
APOE
ε2 / ε4, modify the effect of BP.

Methods:
We prospectively collected demographic and medical data for 608 consecutive ICH survivors, presenting to a single center from January 2006 to December 2013. APOE genotyping was performed on samples obtained via peripheral venous blood draw. Participants were followed longitudinally with periodic BP measurements and evaluation of recurrent ICH / ischemic stroke events. We assessed cognitive and psychiatric outcomes of interest using two validated scales: 1) Telephone Interview for Cognitive Status (TICS); 2) 4-item version of the Geriatric Depression Scale (GDS-4). We generated multivariable Cox models for each outcome, and for overall risk of clinical deterioration (i.e. developing any outcome of interest).

Results:
APOE
ε4 and systolic BP (SBP) interacted to increase risk of ICH recurrence, small vessel ischemic stroke, dementia, and gait impairment after ICH (all p < 0.05). Among patients with average SBP 120-129 mmHg only ε4 carriers were at increased risk for clinical deterioration (Hazard Ratio = 1.67, 95% Confidence Interval 1.06-2.64, p = 0.029). ICH survivors with SBP≥130 mmHg were also at increased risk, with APOE genotype further increasing risk among those with one or more ε4 copies (Figure).

Conclusions:
APOE
ε4 modifies the effect of BP on clinical deterioration risk following ICH, and may identify individuals most likely to benefit from aggressive BP reduction. These data raise the possibility of genetic screening informing hypertension treatment goals in ICH survivors.
Abstract 55: An Integrated Stroke Practice Unit Model Can Impact Blood Pressure Management Post-Stroke
Authors: Commiskey Patricia , Gaines Kenneth
Published: June 2021

Introduction:
Stroke care involves multiple mechanisms and high risk and cost. Even when initial acute events are managed successfully, patient risk remains high for stroke recurrence and readmission for stroke-related causes that negatively impact recovery. Hypertension, the main modifiable risk factor for stroke, accounts for ≤50% of recurrent strokes. Blood pressure (BP) management for stroke post-discharge often combines risk education, lifestyle modification, and medication compliance, but insufficient evidence has complicated provider response.

Methods:
An Integrated Stroke Practice Unit (ISPU) Model was implemented in New Orleans (2012-2015) that combines integrated technology and real time response to improve care coordination from symptom onset through 12-months post-discharge.
Stroke Central
included patients hospitalized with suspected stroke symptoms, and
Stroke Mobile
included patients discharged with a stroke diagnosis residing in St. Tammany or Jefferson Parishes. Stroke Mobile patients were followed at home monthly to assess recovery, manage comorbidities, and provide risk/recovery/recurrence education and caregiver/family support; comprehensive BP management and education were key goals. BP at goal was defined as 140/90 and was measured at each visit (12 total); BP issues were proactively followed and resolved.

Results:
From February 2013-December 2015, 558 patients were seen at least one time in Stroke Mobile, and 192 patients completed 12 visits. Of those who completed the program, patients whose blood pressure was controlled at each visit ranged from 78.2%-93.2%, which is higher than in previously reported studies. Overall, increased control was seen overtime from visits 1-12; additional analyses will examine this in more detail.

Conclusions:
A comprehensive ISPU approach, combined with targeted education and caregiver/family focus, can be effective for managing BP post-stroke.
Abstract 56: An Exome Array Analysis of Ischemic Stroke in the Genetics of Early Onset Stroke Study
Authors: Cole John W , Jaworek Thomas , Ryan Kathy , McArdle Patrick , Dave Tushar , Stine Oscar C , Cheng Yuching , Aparicio Hugo , Yang Qiong , Mei Hao , Grove Megan L , Flaherty Matthew , Kittner Steven J , Wilson James G , Seshadri Sudha , Mitchell Braxton D , Xu Huichin
Published: June 2021

Background:
Ischemic stroke is a heterogeneous trait and its genetic architecture is poorly understood. The genetic contribution may be stronger for stroke occurring at younger (vs. older) ages. To identify additional stroke susceptibility variants, we genotyped participants in the Genetics of Early Onset Stroke (GEOS) with the exome array and conducted association analyses with the goal of identifying functional risk variants by interrogating the protein-coding portion of genes.

Methods:
The GEOS Study was initiated as a biracial population-based study of cases with first-ever ischemic stroke 15 to 49 years of age (n=828) and matched controls (n=850). All participants underwent exome-chip genotyping. Logistic regression was used to calculate associations in European-Caucasians (EUR) and African-Americans (AA), and summary results were combined by meta-analysis.

Results:
Our analyses revealed four highly associated variants for all-stroke and several others that were stroke subtype specific. Among these for all-stroke, we identified a missense variant in
VWDE
(rs6460939 (K (AA
G
) --> N (AA
C
)), which encodes the Von Willebrand Factor D and EGF domain-containing protein. This protein plays a role in intracellular calcium ion binding within a variety of cell-types. The association was present in both European-Caucasians (OR = 1.34, p = 0.002) and African-Americans (OR = 1.32, p = 0.01), and was strengthened in a meta-analysis of both ethnic groups (OR = 1.41, p = 8.95 х 10
-6
). The frequency of the effect C allele was 0.46 in EUR and 0.55 in AA. Efforts in additional data sets to further replicate this association, and the others identified, are ongoing.

Conclusion:
Exome-based analyses in the setting of young-onset stroke is a productive methodology to identify genetic risk variants.
Abstract 61: A Novel Catalytic Antioxidant Carbon Nanoparticle Improves Outcome in Hyperglycemic Stroke in Rats at Clinically Relevant Recanalization Times
Authors: Kent Thomas A , Rea Harriett C , Dalmeida William , Fabian Roderic H , Tour James M , Nilewski Lizanne G , Sikkema William , Mandava Pitchaiah
Published: June 2021

Introduction:
While oxidative stress mediates many of the pathologies in stroke, antioxidant therapies have been unsuccessful. Current antioxidants are limited either by a narrow range of radicals quenched or by low capacity. Some can yield toxic intermediates. We developed a new class of antioxidant, highly modified carbon nanoparticles called PEGylated hydrophilic carbon clusters (PEG-HCCs). These 40 nM particles quench superoxide by a high capacity novel catalytic mechanism (PNAS 2015: 2343-8), are effective against
-
OH and recouple nitric oxide synthase. Here we report the effect of PEG-HCCs administered during reperfusion after transient MCA suture occlusion in the rat under varying glucose levels. Hyperglycemia occurs in 1/3 of stroke patients and worsens outcome in part by accelerating release of radicals during reperfusion.

Methods:
Variation in glucose was induced by streptozocin IP 2 days prior to MCAO. At 90 mins, 23 rats were injected IV with PBS or PEG-HCCs (4 mg/kg) and the suture removed. A second dose was given 2 hours later (dosing based on half-life and in-vitro efficacy). At 3 days, infarct size corrected for edema and neurological function (Bederson Score, BS) was obtained. An outcome curve was developed using a range of baseline glucose in controls and the effect of PEG-HCCs compared at rat’s baseline glucose values.

Results:
We found a strong sigmoidal relationship between infarct size and glucose level in control rats (Fig. R
2
=.93; p=.0001; blue curve: control arm ± 95% confidence intervals). All PEG-HCC treated rats showed infarct size below the confidence interval (red stars; p<.003 vs control). Preliminary results for 120 min occlusion showed improved BS compared to control (3.5±2.4 vs 5.4±1.8; p=.047).

Conclusions:
This novel, broadly active, high capacity antioxidant was able to improve outcome in a severe test of pre-clinical stroke at clinically relevant times. Studies are ongoing to assess the treatment window and longer term outcomes.
Abstract 82: Diastolic Dysfunction Revealed by Transesophageal Echocardiography Predicts New Atrial Fibrillation During Hospitalization for Acute Ischemic Stroke
Authors: Tateishi Yohei , Kanamoto Tadashi , Nakaoka Kenjiro , Morofuji Yoichi , Horie Nobutaka , Izumo Tsuyoshi , Tsujino Akira
Published: June 2021

Background:
Transesophageal echocardiography (TEE) is often performed to explore an embolic source in ischemic stroke patients without atrial fibrillation (AF). The aim of this study was to elucidate the relationship between the ratio of transmitral flow velocity (E) and mitral annular velocity (e’) measured by using TEE (E/e’ TEE) and prediction of new AF during hospitalization.

Method:
We prospectively enrolled 170 patients with acute ischemic stroke without known atrial fibrillation at admission. Transthoracic echocardiography was performed to assess left atrial diameter, ejection fraction, and E/e’. A subset of patients underwent TEE to explore an embolic source. We obtained the e’ at the lateral wall located near the left atrial appendage by using TEE. Baseline characteristics, stroke features, initial National Institutes of Health Stroke Scale (NIHSS) score, plasma and serum biomarkers included brain natriuretic protein (BNP), and imaging findings were recorded. We investigated factors to predict new documented AF by multivariate logistic regression analysis. To elucidate the cut off value of factors for predicting new AF, the area under the curve of the receiver operating characteristic curve was evaluated.

Results:
AF was detected in 14 patients (8%). In univariate analysis, older age (median, 75 years vs. 71 years; p=0.022), higher initial NIHSS score (median, 8 vs. 3; p=0.017), elevated plasma BNP level (median, 183 pg/mL vs. 36 pg/mL; p<0.001), larger left atrial diameter (median, 38 mm vs. 35 mm; p=0.024) and higher E/e’ TEE (median, 22.4 vs. 14.4; p=0.004) were positively associated with new documented AF. In multivariate analysis, E/e’ TEE was an independent predictor of newly diagnosed AF during hospitalization (Odds ratio, 1.680; 95% confidence interval, 1.174 to 3.420; p<0.001). The cut off value of E/e’ TEE for predicting new AF was 21.5 with the sensitivity of 80 % and the specificity of 98 %.

Conclusions:
Diastolic dysfunction evaluated by TEE may be a good predictor of newly diagnosed AF.
Abstract 83: Etiology of Late Right-to-Left Shunting on Transcranial Doppler in Ischemic Stroke Patients
Authors: de Havenon Adam , Moore Anne , Freeberg Nicholas , Sultan-Qurraie Ali , Tirschwell David
Published: June 2021

Background:
An echocardiogram or transcranial Doppler (TCD) bubble study to test for a right-to-left shunt (RLS) is a standard component of an ischemic stroke workup. Because the pathway for an intracradiac RLS, such as a patent foramen ovale (PFO), is more direct, it has been proposed that the late appearance of a RLS suggests an extracardiac pathway. We sought to characterize a cohort of ischemic stroke patients with late RLS (LRLS) on TCD.

Methods:
We searched the medical record of a Comprehensive Stroke Center for patients with ischemic stroke who had a TCD and echocardiogram bubble study during 2011-2013. LRLS was defined as TCD bubbles appearing more than 18 cardiac cycles after contrast injection. TOAST stroke etiology classification was performed by a vascular neurologist blinded to TCD results.

Results:
124 patients met inclusion criteria, of which 67/124 (54%) had RLS on TCD; and 32/67 (48%) had LRLS. In the 35/67 patients with normal RLS on TCD, 23% did not have RLS on echocardiography, consistent with prior reports of TCD’s superiority for detecting RLS. In the 32/67 patients with LRLS on TCD, 56% were negative for RLS by echocardiography. In the cohort of 124 patients, the percentage of TOAST classification 4 (stroke of other determined cause) was 26%, while in the 32 patients with LRLS the percentage of TOAST 4 was significantly higher at 52%(p=0.005) (Table 1). The increase in TOAST 4 in LRLS patients was created by an even distribution of decreases in the other TOAST categories. The most common TOAST 4 stroke etiology in LRLS patients was PFO with concurrent deep venous thrombosis.

Conclusion:
This preliminary data supports prior studies that have shown superiority of TCD over echocardiography for detection of RLS, and challenge the prevailing notion that extracardiac shunt, such as pulmonary AVM, is the most common cause of LRLS in ischemic stroke patients. This subgroup of patients warrants further research to clarify mechanisms of ischemic stroke in patients with RLS.
Abstract 9: Diffusion Tensor Tractography Correlates of Post-Stroke Spasticity & Its Mitigation
Authors: Pundik Svetlana , Skelly Margaret , McCabe Jessica , Akbari Heba , Daly Janis J
Published: June 2021

Purpose:
Anatomical localization of brain networks controlling post-stroke spasticity are not fully understood. The purpose of this study was to determine the relationship between the integrity of white matter tracts and severity of spasticity and how this relationship changes with mitigation of spasticity in response to motor learning therapy.

Methods:
Eleven stroke survivors (>6 months post-stroke) with arm sensorimotor deficits had 12-week (5 d/week, 5 hr/day) motor learning therapy. Outcome measures included modified Ashworth Scale (mAS), Fugl-Meyer Upper limb (FM) and Diffusion Tensor Imaging (DTI). mAS was scored for 9 arm muscles and summated. Using Freesurfer software, DTI was analyzed via longitudinal processing stream and white matter tracts were reconstructed according to a global probabilistic tractography algorithm. Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were averaged along the center of the 8 bilateral and 2 interhemispheric white matter tracts. We performed partial Spearman correlation (Bonferonni correction for multiple comparisons) to evaluate the relationship between mAS and DTI measures while controlling for change in Fugl-Meyer. Wilcoxon paired sign rank test was used to compare pre vs post rehab scores for mAS and FM.

Results:
Subjects were 59±8.3 years old, 46±30 months after stroke and 54% were female. mAS improved from 5.95±3 to 3.95±2.6 (p=0.002, paired sign rank test) and FM improved from 25.9±12.4 to 37.6±13.9 (p=0.00097). At baseline, lower spasticity correlated with higher AD in the ipsilesional cingulum angular bundle (rho=.86; p=0.0007). Greater improvement in spasticity correlated with lower AD in the contralesional uncinate fasciculus (rho=.79;p=0.004) at baseline. Both tracts are part of limbic system. Furthermore, lower spasticity at baseline correlated with lower FA in the contralesional corticospinal tract (rho=.81; p=0.004) at baseline.

Conclusion:
The results show the complex nature of anatomical localization for spasticity and its mitigation. Structural integrity of the contralesional corticospinal tract as well as bi-hemispheric limbic system tracts may be involved in post-stroke spasticity.
Abstract 94: Prevalence and Distinct Imaging Correlates of Deep Versus Lobar Cerebral Microbleeds: The Atherosclerosis Risk in Communities Study
Authors: Graff-Radford Jonathan , Simino Jeannette , Mosley Thomas H , Griswold Michael E , Windham Beverly G , Gottesman Rebecca F , Sharrett Albert R , Albert Marilyn , Jack Cliff R , Kantarci Kejal , Vemuri Prashanthi , Knopman David S
Published: June 2021

Introduction:
Cerebral microbleed (CMB) location may predict underlying pathology. Deep CMBs are more associated with hypertensive vascular disease, while lobar CMBs are more associated with cerebral amyloid angiopathy (CAA). The objective of this study was to determine the neuroimaging pathology associated with CMBs.

Methods:
We analyzed 1,831 nondemented ARIC participants (mean age=76.3 ±5.3 years, 40% male, 27% black) with 3T MRI scans at the fifth exam (2011-13). We fit multinomial logistic regression models to assess the effect of brain volumes (AD signature region atrophy, total gray matter, frontal, and log
2
-transformed white matter hyperintensities (WMH) volume), infarct frequencies (lacunar, non-lacunar, and total), and
APOE
(number of ε4 alleles) on CMB location (no, any deep, or lobar only CMBs). Models were weighted for the sample selection scheme and adjusted for age, male, education, hypertension, ever smoking status, diabetes, race-site membership, and estimated intracranial volume (brain volume models only).

Results:
The frequency of CMBs was 24.1%. A larger WMH volume, greater total infarct frequency, and smaller total grey volume increased the relative risks (RR) of both deep and lobar CMBs compared to no CMBs; increasing the WMH volume also increased the RR of deep to lobar CMBs. Additional lacunar infarcts increased the RR of deep compared to no CMBs, whereas AD signature region atrophy and
APOE
ε4 homozygosity increased the RR of lobar CMBs.

Conclusion:
CMBs are a common vascular pathology in the elderly. Deep CMB presence is associated with MRI features of hypertensive small vessel disease, while lobar CMB presence is associated with MRI features of CAA and Alzheimer’s disease.
Abstract NS1: Development of the Preparedness Assessment for the Transition Home After Stroke (PATH-s) Instrument
Authors: Camicia Michelle , Lutz Barbara
Published: June 2021

Introduction:
Care transitions from the inpatient rehabilitation facility (IRF) to home after stroke are often ineffective and inefficient, resulting in unmet patient and caregiver needs, increased safety risks, high rates of preventable readmissions, and increased health care costs. There is no assessment instrument specifically designed to evaluate caregiver readiness for this transition. The purpose of this study is to describe the development of the Preparedness Assessment for the Transition Home after Stroke (PATH-s) instrument.

Methods:
A cross-sectional study was conducted to establish the psychometric properties of the PATH-s instrument using a convenience sample of 60 caregivers of stroke patients with moderate to severe impairment during IRF admission. A sequential, multi-method approach to instrument development beginning with item generation from qualitative research findings followed by (a) review of items by expert case managers, (b) development of an alternative Likert format, (c) selection of the format that provides greatest clarity, and (d) cognitive appraisal interviews with caregivers with associated instrument revision was used to develop a measure of readiness for the transition from IRF to home for stroke caregivers.

Results:
The novel PATH-s instrument is a 15-item, 4-point scale that has demonstrated validity. Next steps include additional psychometric testing of the PATH-s to understand the predictive validity to stratify the degree of risk of adverse health effects for stroke survivors and caregivers following transition from the IRF to home.

Conclusion:
The PATH-s may support a primary prevention strategy to identify gaps in preparedness for stroke survivor-caregiver dyads during this high risk transition, with the long-range goal to mitigate the effects of suboptimal preparation and the associated adverse effects associated with this transition on the health of stroke survivor and caregiver. Once gaps are identified, care plans can be tailored to address gaps and better prepare caregivers for the transition home. This optimized approach to transitions management will address the National Quality Strategy “Triple Aim” to improve quality of care, improve health, and reduce costs for the care delivery system.
Abstract NS2: RACE to Treat Stroke: The Results
Authors: Korsnack Andrea M
Published: June 2021

Background:
In June of 2015
we
revised the County-Level Emergency Medical Services (EMS) protocol and algorithm to include the Rapid Arterial oCclusion Evaluation (RACE) scale in addition to the Cincinnati Prehospital Stroke Scale (CPPS) to determine if first responders could differentiate between which stroke patients could benefit from endovascular treatment using this simple algorithm. Preliminary data showed that first responders can accurately differentiate between which stroke patients could benefit from endovascular treatment but does it increase treatment rates and decrease treatment times?

Purpose:
To determine if first responders transporting stroke patients to the closest Interventional Stroke Center for treatment increased the number of stroke patients receiving interventional treatment and/or intravenous tissue plasminogen activator (IV tPA) and does door to needle and door to computerized axial tomography scan (CT) times decrease?

Method:
We analyzed the number of thrombectomies done and the number of patients receiving IV tPA from July 2014 to June 2015 (before implantation of the RACE protocol) compared to July 2015 to June 2016 (after implantation of the RACE protocol) and examined our door to needle and door to CT scan times over the same period.

Results:
EMS brought 56 ischemic stroke patients to our primary stroke center from July 2014 to June 2015. 10 patients received IVtPA (17.8%) and 5 underwent thrombectomies (8.9%). EMS brought 83 ischemic stroke patients to our primary stroke center from July 2015 to June 2016 using the RACE protocol. 29 patients received IVtPA (34.9%) and 18 underwent thrombectomies (21.7%). Our door to needle times for IVtPA decreased from a median of 64 minutes to 37 minutes, and door to CT times decreased from a median of 24 minutes to 13 minutes over the same time period.

Conclusion:
Our data suggests that if first responders transport patients using the RACE protocol, a greater percentage of stroke patients will be eligible for endovascular treatment and use of IV tPA and treatment times can also be improved. Future evaluation could measure the outcomes of these patients using the Modified Rankin Score (mRS).