bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 135: MicroRNA 133b Promotes Neural Plasticity Via Exosome Transfer After Treatment Of Stroke With Mesenchymal Stromal Cells In Rats
Authors: xin hongqi , Li Yi , Liu Zhongwu , Cui Yisheng , Zhang Zheng G , Chopp Michael , Chopp Michael
Published: July 2021

Introduction:
Our previous in vitro study demonstrated that MSCs via exosomes transfer miR-133b to neural cells which promote neurite outgrowth. In the present in vivo study, we altered the miR-133b level in MSC exosomes, and tested neural plasticity and functional recovery after MSC treatment of stroke in rats.

Methods:
We generated stable rat MSC cell lines with transfection of pre-miR-133b (miR-133b+MSC) and miR-133b inhibitor (miR-133b-MSC). Adult Wistar rats were subjected to 2h MCAo and intravenously received MSCs (3x106) or PBS at 24h after MCAo. Functional tests (Neurological Severity Score and Foot Fault) were performed. Rats were sacrificed 14 days after MCAo and adjacent frozen coronal sections were used for immunostaining. Western blot and TaqMan miRNA assay were used to detect protein and miR-133b.

Results:
The miR-133b levels in MSCs and their corresponding exosomes were increased in miR-133b+MSCs (652.1±54.1% and 367.4±21.6%, respectively), and were decreased in miR-133b-MSCs (33.5±4.4% and 21.0±8.1%, respectively) compared to normal MSCs. At day 14 after MCAo, all MSC treatment groups except miR-133b-MSCs improved (P<0.05) functional recovery compared with PBS treatment, and miR-133b+MSCs improved (P<0.05), while miR-133b-MSCs treatment decreased (P<0.05) functional recovery compared to normal MSCs. Bielshowsky silver, NF-200 and synaptophysin staining showed that neurite remodeling increased along the ischemic boundary zone (P<0.05) after normal MSC treatment and were enhanced by miR-133b+MSC treatment (36.4±4.3%, 12.2±5.2% and 21.6±5.6%, respectively). Compared to MCAo control, normal MSC treatment increased (P<0.05) the miR-133b level in the CSF exosomes, which was further increased by miR-133b+MSCs (101.1±13.2%) and significantly decreased by miR-133b-MSCs (73.9±10.1%). MCAo increased RhoA and CTGF (target proteins of miR-133b, P<0.05, respectively) expression in rat brain and miR-133b+MSC treatment further reversed protein expression at day 14 after MCAo compared to normal MSCs.

Conclusions:
In concert with our in vitro data, the present study indicates that MSC treatment promotes neural plasticity and functional recovery after stroke by transferring miRNAs (e.g. miR-133b) to neural cells via exosomes.
Abstract 145: Is the Rate of Ischemic Stroke Incidence Changing Differentially Over Time for Women and Men?
Authors: Khoury Jane C , Kissela Brett , Sucharew Heidi , Alwell Kathleen , Moomaw Charles , Woo Daniel , Flaherty Matthew , Adeoye Ope , Khatri Pooja , Ferioli Simona , Broderick Joseph , Kleindorfer Dawn
Published: July 2021

Background:
A surge of midlife (age 55-64 years) stroke in women, and not in men, has previously been reported using prevalence data from NHANES. However it is not clear if this same finding would be seen within age- and gender-specific incidence rates of stroke. We sought to examine the incidence of ischemic (IS) stroke and the gender-specific trends over time in a population-based study of stroke epidemiology.

Methods:
Data from the population-based Greater Cincinnati and Northern Kentucky epidemiology of stroke study for adults (≥ 20 years) was used from three collection periods; 7/1993 to 6/1994, 1999, and 2005. We compared the IS stroke incidence rates in women versus men between the three study periods, in particular for the ages 35 to 65 years. Sex specific age, and race adjusted incidence rates and race adjusted, age and gender specific incidence rates were estimated and adjusted to the 2000 US population.

Results:
A total of 5166 incident IS strokes were identified: 1709 from 7/1993 to 6/1994, 1778 from 1999, and 1679 from 2005. These were 56% female, 18% black; mean age was 71.4 (13.7) years. Overall, IS stroke incidence declined in both women and men in 2005 compared to the previous time periods (p<0.01). However, there was a significant increase over time in stroke incidence seen in both men and women in the younger age groups in 2005, compared with 1993/94 (p<0.05).

Conclusions:
We found that stroke incidence is not changing differently over time for men and women. There has been an increase in IS stroke incidence in the young, but this is found in both men and women. The previously reported “surge” in middle-aged stroke prevalence may be related in part to increased rates of stroke in the young, with survival to middle-age, but our incidence findings do not explain the reported difference in prevalence found between women and men in the NHANES cohort.
Abstract 146: Cerebral Microbleeds: Prevalence and Risk Factors in the Framingham Study
Authors: Romero Jose R , Preis Sarah R , Beiser Alexa S , Viswanathan Anand , Martinez-Ramirez Sergi , Kase Carlos S , Wolf Philip A , DeCarli Charles , Seshadri Sudha
Published: July 2021

Objective:
To assess the prevalence of CMB in a middle-aged to elderly community-based cohort and explore the association of cardiovascular risk factors (CVRF) and medication use to CMB occurrence and location.

Background:
CMB have been associated with increased risk of stroke and dementia. CVRF and some medications used for stroke prevention may increase the risk of CMB. We hypothesized that these associations would vary according to CMB location, since location is determined by underlying vascular pathology, lobar CMB due to CAA and deep CMB due to hypertensive vasculopathy.

Methods:
1,965 Framingham Original and Offspring Cohort participants (age [mean (SD)] 66.5±11.0years; 54% women) who attended a baseline examination between 1998 and 2008 and also had a brain MRI with T2*GRE sequences were included. We evaluated age- and sex-specific prevalence of CMB. Using linear and logistic regression models we related various CVRF, APOE status and stroke prevention medications to presence of any CMB and to risk of CMB stratified by brain location.

Results:
CMB were observed in 8.8% (n=173) of participants. 63% had only lobar CMBs, 22% deep and 15% had CMBs in both locations. CMB prevalence increased with age (p<0.0001) and was higher in men (p<0.001). Hypertension (HTN), HTN treatment and statin use were overall predictors of CMB (p<0.05). APOE ε4 and statin use were the only predictors for lobar CMB (p<0.05). HTN, HTN treatment, antiplatelet use and statin use were associated with greater risk of deep CMB (p<0.05). Diabetes, smoking and serum lipid levels were not associated with CMB prevalence. Participants with mixed CMB (lobar/deep) showed a similar pattern of associations as persons with only deep CMB.

Conclusions:
Our results support findings in older cohorts of higher CMB prevalence with age and in men, an association of HTN, HTN treatment, statins and antiplatelet agents with deep, and of APOE ε4 genotype and statins with lobar CMB. Although we observed an association of statin use with CMB neither total cholesterol, nor HDL level, was associated with CMB risk. These findings expand our understanding of CMB pathophysiology, and will be extended by exploring associations with other biomarkers (such as inflammatory markers) and incident CMB.
Abstract 169: Circulating Il-6 And Il-18 Levels Are Associated With The Risk Of Incident Dementia In Patients With Vascular Risk Factors
Authors: Miwa Kaori , Tanaka Makiko , Okazaki Shuhei , Furukado Shigetaka , Sakaguchi Manabu , Mochizuki Hideki , Kitagawa Kazuo
Published: July 2021

Background and Purpose:
Association between circulating inflammatory marker and future dementia has not been fully investigated. To what extent inflammatory markers impact future dementia beyond small vessel disease (SVD) and brain atrophy on MRI is unknown. We sought to determine the predictive value of circulating inflammation marker (high-sensitivity C-reactive protein [hsCRP], interleukin [IL]-6, and IL-18), when controlling for MRI measures of SVD (lacunar, white matter hyperintensity [WMH]) and brain atrophy on the risk of dementia.

Methods:
We enrolled 480 outpatients (median 68 years, male 58%, 12.8±2.4 years of schooling ) who had vascular risk factors but without dementia. At baseline, demographic information, brain MRI, and cognitive function testing were performed. We also measured hsCRP, IL-6, and IL-18. Baseline MRI was used to determine SVD (lacunar and WMH) and atrophy (cortical and subcortical). Cox proportional hazards analysis was performed as predictors of dementia with adjusting for age, gender, APOE4 allele, educational level, history of clinical stroke, conventional vascular risk factors, baseline Mini-Mental State Examination score and MRI-findings.

Results:
At end of follow-up (median 7.5 years duration), 40 patients had dementia (Alzheimer disease:21 patients, vascular dementia:16 patients, other type dementia:3 patients) In the age, gender, education level, and APOE4 allele-adjusted models, WMH severity, number of lacunar, atrophy, previous stroke, smoking and baseline MMSE-score were associated with incident dementia. Among inflammatory markers, both IL-6 and IL-18, but not hsCRP, were associated with dementia (IL-6; HR:2.10, 95% CI [1.21-3.58], IL-18; HR:3.32, 95% CI [1.52 -7.28], hsCRP; HR:1.08, 95% CI [0.80-1.46]) (per 1-SD increase in log-transformed inflammatory markers). These associations of both IL-6 and IL-18 with dementia remained significant even after additional adjusting for MRI-findings and confounding variables

Conclusion:
Our longitudinal study showed that both IL-6 and IL-18 levels are independently related to the risk of dementia in patients with vascular risk factors. Our results support the hypothesis that inflammation exerts deleterious effects on dementia incidence.
Abstract 18: Improving Door-to-Needle Times with Target Stroke
Authors: Ruff Ilana M , Syed Ali , Rost Natalia , Goldstein Joshua , Lev Michael , Copen William , McIntyre Joyce , Schwamm Lee
Published: July 2021

Introduction:
Nationally, fewer than 30% of IV tPA-treated patients are imaged within 25 minutes, or receive IV tPA within 60 minutes of ED arrival. In 2007, we implemented a new institutional acute stroke care model to include 10 best practices, all of which were later included in AHA’s Target Stroke program. We evaluated the effect of this strategy on timeliness of acute ischemic stroke (AIS) care.

Methods:
We analyzed median ED door-to-CT (DTCT) and door-to-needle (DTN) times in 4,477 AIS patients enrolled in our Get with the Guidelines Stroke registry from 2003-2011. Predictors of DTN ≤ 60 min (DTN60) were assessed using Chi-square for categorical variables and t-test for continuous variables.

Results:
An initial CT scan was performed in our ED in 58% of AIS patients, 289 of whom received IV tPA. Median DTCT times and DTN60 dropped significantly among tPA-treated patients after the intervention (Table 1, Chart 1). The percentage of patients with DTCT ≤ 25 min and DTN60 doubled post-intervention [12.6% vs. 28.1% and 35.0% vs. 70.0%, respectively, p <0.001]. Patients with DTN60 did not differ significantly in age, gender, race, co-morbidities, or NIHSS score as compared to those treated >60 min.

Conclusion:
Implementing the AHA Target Stroke best practices improved DTCT and DTN60 times for AIS patients, doubling the percent of patients meeting recommended targets. Only calendar year was independently associated with achieving DTN60, demonstrating a step function improvement after the guidelines were systematically applied. Therefore, changes in hospital-level, rather than patient-related factors are driving improvement.
Abstract 186: Intra-Arterial Chemotherapy Opens New Horizons to Neurointerventional Surgeons
Authors: Chalouhi Nohra , Tjoumakaris Stavropoula , Dumont Aaron S , Gonzalez L Fernando , Shields Carol , Bianciotto Carlos G. , Rosenwasser Robert , Jabbour Pascal
Published: July 2021

Introduction:
Intra-arterial chemotherapy (IAC) consists of delivering chemotherapeutic agents precisely into tumor vessels, minimizing systemic toxicity. At our institution, we have utilized this technique to treat children with advanced and extensive retinoblastomas. We assess the safety and efficacy of IAC in a large series of patients, with special emphasis on technique-related complications.

Methods:
Between 2010 and 2012, a total of 151 IAC procedures were performed at our institution. The ostium of the ophthalmic artery was superselectively catheterized followed by injection of chemotherapeutic agents in a pulsatile fashion over 30 minutes. Patients were closely observed post-operatively and discharged the same day. Data on procedural safety were prospectively collected.

Results:
Catheterization was successful in 98% of the procedures. Technical complications occurred only in 2 cases (1.3%). One patient with anomalous internal carotid artery had a severe spasm during cannulation and the procedure was aborted. He remained neurologically intact post-operatively. Another patient had two asymptomatic tiny foci of diffusion restriction on cerebral magnetic resonance imaging. No patient developed a retroperitoneal hematoma, acute limb ischemia, carotid dissection, or intracerebral hemorrhage. Tumor response was found in 88% of cases with globe salvage in 67%. There was no incident of metastasis, secondary tumor, or death.

Conclusion:
With proper technique and instrumentation, IAC can be performed with a technical complication rate as low as 1.3% and a morbidity rate of 0%. Our successful experience with IAC opens new horizons to Neurointerventional Surgeons involved in the care of patients with intracranial malignancies.
Abstract 203: Longterm Assessment Is Important in Patients Undergoing Decompressive Craniectomy for Malignant Middle Cerebral Artery Infarction
Authors: Bhatia Rohit , Rai Vinod , Singh Shaily , Padma M V , Prasad Kameshwar , Tripathi Manjari , Singh Mamta Bhushan , Suri Ashish
Published: July 2021

Objective:
Decompressive hemicraniectomy (DC) has been shown to reduce mortality among patients with malignant middle cerebral artery ( MCA) infarction in short term. The present study aimed at studying the long term functional outcome of patients undergoing DC for malignant MCA infarctions.

Methods:
All patients malignant MCA infarction requiring DC were prospectively enrolled. Patients meeting the inclusion criteria but not undergoing surgery due to any reason were taken as controls. Aphasia testing using was done using Western Aphasia Battery. Modified Rankin Scale (mRS) was done at 3, 6 and12 months to grade functional outcome. mRS ≤ 3 was defined as a good outcome.

Results:
60 patients were enrolled during the study period. Mean age was 49.6 years with 72% males. 36 patients (60%) underwent decompressive hemicraniectomy (surgery group) and 24 (40%) received best medical management only (medical group). Mean delay to surgery from time of onset of symptoms was 56 hours (9-148). One year follow up completed for 57 patients and 35 patients (61.4%) died over a period of 1year. Significantly high mortality was noted in the control group at discharge, 3, 6 & 12 months. Cumulative risk of death was 83% in controls compared to 38% in surgical group at 1 year. 2.78% (1/36),16.67% (6/36) and 20% (7/35) patients achieving good outcome at 3, 6 and 12 months in the surgery group and none in controls. Repeated ANOVA showed progressive improvement over time from 3 to 6 months (p< 0.01), 3 months to 1year (p< 0.001), and 6 months to 1 year (p<0.019). Mean aphasia quotient improved progressively over time.

Conclusions:
Decompressive hemicraniectomy leads to a increased and functionally better survival compared to medical management alone. The outcome assessment at 3 months underrepresants the benefits in trials. For life threatening strokes it is prudent to make assessment at longer intervals. There is progressive improvement in aphasia over time in the surgically survived group
Abstract 25: Caregiver Task Difficulty, Task Time, Optimism, Threat, Depressive Symptoms, and Life Changes Comprise Four Latent Classes of Stroke Caregivers
Authors: Weaver Michael T , McLennon Susan M , Jessup Nenette M , Bakas Tamilyn
Published: July 2021

Background:
Providing care for a stroke survivor often times results in alterations of social and psychological functioning for caregivers. The ability to identify classes of responses may be useful to identify at-risk caregivers and intervention programs to meet specific needs.

Purpose:
The purpose of this exploratory analysis was to identify classes of stroke caregivers based on Caregiver Task Difficulty, Task Time, Optimism, Threat, Depressive Symptoms, and Life Changes, all factors that are important components of the caregiving experience.

Methods:
Baseline data on Caregiver Task Difficulty (OCBS), Task Time (OCBS), Optimism (LOT-R), Appraisal of Caregiving Threat (ACS), Depressive Symptoms (PHQ9), and Life Changes (BCOS) from 176 caregivers enrolled in an ongoing stroke caregiver intervention study (TASK II) were analyzed using Latent Profile Analysis. Number of latent classes and adequacy of fit were evaluated using Bayes Information Criteria (smallest value), Entropy (>.80), and parametric bootstrapped likelihood ratio tests
(p
< .05) produced by MPlus version 6.11.

Results:
The typical caregiver was female (76%), White (71%), 53.4 years of age (SD=12.6), not employed (58%), spouse (45%) of the stroke survivor. Four latent classes were identified: (1) relatively low OCBS difficulty and time, low LOT-R optimism with relatively high ACS threat and PHQ9 and negative BCOS life changes; (2) relatively low task difficulty and time, high LOT-R, low ACS and PHQ9, and positive BCOS life changes; (3) moderate task difficulty and time, LOT-R, ACS, PHQ9, and BCOS; and (4) high task difficulty and time, low LOT-R, and high ACS, PHQ9, and negative BCOS life changes.

Conclusions:
While needing future empirical validation, the four latent classes suggest 4 responses to caregiving that may be useful to (a) identify caregivers at risk for adverse outcomes, (b) tailor intervention programs, and (c) evaluate response to those interventions.
Abstract 41: Targeting the Neurovascular Bed by Co-delivery of Therapeutics for Synergic Stroke Treatments
Authors: Peng Tao , Miao Yi-Feng , Britton George L , Kim Hyunggun , McPherson David D , Huang Shaoling
Published: July 2021

BACKGROUND:
Due to the multifaceted pathology of neurovascular damage in stroke, providing combined therapies aimed at underline different mechanisms may be a promising strategy. We have demonstrated that echogenic liposomes (ELIP) can effectively deliver xenon (Xe), a
N
-methyl-D-aspartate receptor antagonist, into brain tissue for dose-dependent neuroprotection. This study evaluates the synergic therapeutic effects of ELIP delivering Xe with an anti-inflammatory gas, hydrogen sulfide (H
2
S), or a free radical scavenger, hydrogen (H
2
), in a rat stroke model.

METHODS:
A gas mixture of 1% H
2
S with 99% Xe or 30% H
2
with 70% Xe was loaded into ELIP by a pressurization-freeze method. Rats (n=25) undergoing 2-hour middle cerebral artery occlusion were then treated with low-dose Xe-ELIP, H
2
S/Xe-ELIP, or H
2
/Xe-ELIP, respectively, at 3 hours after stroke onset. One MHz low-amplitude (0.18 MPa) ultrasound was directed over the internal carotid artery to trigger gas release. Behavioral tests were conducted for three days following surgery. After sacrifice, brain sections were evaluated for infarction and apoptotic neuronal death using triphenyltetrazolium chloride (TTC) and TUNEL staining. Infarct size was evaluated as normalized infarct volume (%).

RESULTS:
Strokes without treatment had an infarct size of 27± 6%. Strokes with Xe-ELIP treatment exhibited an infarct size of 20±4% (p=0.232
vs.
no treatment). Strokes with H
2
S/Xe-ELIP and H
2
/Xe-ELIP treatments demonstrated a further infarct size reduction to 7.1±1.6% (p=0.017
vs.
no treatment) and 8.8±1.9% (p=0.032
vs.
no treatment), respectively. Neurologic behavior tests reflected infarct size.

CONCLUSIONS:
In this study, using echogenic immunoliposomes as a vehicle, co-delivery of therapeutics targeting different mechanisms of neurovascular damage results in a synergic therapeutic effect. This methodology provides an avenue for evaluation of other synergic agents for use in acute stroke.
Abstract 48: Should Acute Ischemic Stroke Patients with Very High National Institutes of Health Stroke Scale Scores Undergo Pre-procedure Intubation Prior to Endovascular Treatment?
Authors: Hassan Ameer E , Adil Malik M , Zacharatos Haralabos , Rahim Basit , Chaudhry Saqib A , Tekle Wondwossen G , Grigoryan Mikayel , Qureshi Adnan I
Published: July 2021

Background:
Due to higher rates of poor outcomes in endovascular procedures under general anesthesia, it has been proposed that only stroke patients with a very high baseline NIHSS score undergo pre-procedural intubation.

Objective:
To determine if patients with very high NIHSS score (>20) can undergo endovascular procedure without pre-procedural intubation and how the outcomes compare to procedures were performed after pre-procedural intubation and mechanical ventilation.

Methods:
All endovascular treated acute ischemic stroke patients identified through a prospective database maintained from two comprehensive stroke centers over a 6-year period. Patients’ risk factors, type of sedation, pre-procedural intubation status, rates of poor outcome at discharge (modified Rankin score [mRS] of >3) and intracerebral hemorrhage (ICH) were obtained and analyzed. The rates of unexpected intubation in patients undergoing procedures without pre-procedural intubation were ascertained.

Results:
Among the total of 93 patients (mean age 68.5 ± 16.4) with NIHSS score > 20, 61% (57 patients, 49% men) underwent endovascular procedures after pre-procedural intubation. Among the 57 patients who underwent the procedure without pre-procedural intubation, the rates of unexpected intubation secondary to intra-procedural complication was 6 (11%). The mean time interval between CT scan to intiation of procedure was significantly greater among patients who underwent pre-procedural intubation (134±34 versus 170±53 minutes, p<0.001). The risk of post-procedure ICH [OR 0.3, 95% CI 0.1-0.8, p=0.01) and in-hospital mortality [OR 0.1, 95% CI 0.07-0.3, p<0.0001] were significantly lower among patients who did not undergo pre-procedural intubation, after adjusting for potential confounders. The rates of poor outcomes at discharge were significantly lower among those patients who underwent the procedure without pre-procedural intubation [OR 0.3, 95% CI 0.1-0.6, p=0.001].

Conclusions:
Despite the risk of unexpected intubation secondary to intra-procedural complication, patients with admission NIHSS score>20 who undergo endovascular treatment without pre-procedural intubation have a decreased risk of poor outcomes, ICH, and death.
Abstract 76: Significance of Paradoxical Central Increased Diffusivity in Perinatal Arterial Ischemic Stroke
Authors: Stence Nicholas V , Bernard Timothy J , Manco-Johnson Marilyn J , Armstrong-Wells Jennifer
Published: July 2021

Objective:
Perinatal arterial ischemic stroke (PAS) is diagnosed by MRI in the acute period after clinical presentation (seizure and/or encephalopathy). Acute MRI stroke protocols include diffusion weighted imaging (DWI), and typically show uniformly restricted diffusion. Yet, a periphery of restricted diffusion with a core of central increased diffusivity (CID) is sometimes observed in PAS (Fig. 1). Given the confusing and paradoxical DWI appearance in those patients, we sought to determine CID significance, and hypothesized that: 1) CID is associated with larger strokes 2) CID tissue is irreversibly injured (infarcted) on follow-up imaging, which may portend worse outcome.

Methods:
We reviewed all PAS cases in our prospective cohort study from 08/01/2000 - 1/01/2012. PAS with DWI in the acute period was identified and assessed for CID by a pediatric neuroradiologist (NVS); confirmation/clinical data abstraction was performed by a pediatric stroke neurologist (JAW). Stroke volumes were measured by drawing regions of interest around the periphery of the area of restricted diffusion on DWI. Mann-Whitney U was performed to compare means between groups.

Results:
Of 25 PAS cases with satisfactory MR imaging, CID was seen in 4 (16%). Patients with CID had larger average stroke volumes (mean 117182 mm3 vs. 36995 mm3; p=0.008), and were more often treated for ongoing seizures at last clinic follow-up (3/4 vs. 0/21; p<0.00001). All CID patients underwent follow-up imaging (range 4-27 months), and the CID tissue was confirmed to have undergone completed infarction.

Conclusion:
In our small PAS sample, CID was associated with larger stroke volume; this tissue with paradoxically increased diffusivity was confirmed as infarcted on follow-up imaging. Patients with CID were more commonly treated for persistent seizures beyond the newborn period. Our data suggest that CID on initial MRI may add prognostic significance in newborns with PAS.
Abstract 79: Troponin T, NT-proBNP, and Incidence of Stroke: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Folsom Aaron R , Nambi Vijay , Bell Elizabeth J , Oluleye Oludamilola W , Gottesman Rebecca F , Lutsey Pamela L , Huxley Rachel R , Ballantyne Christie M
Published: July 2021

Increased levels of plasma troponins and natriuretic peptides in the general population are associated with increased future risk of cardiovascular disease, but only limited information exists on these biomarkers and stroke occurrence. In a prospective epidemiological study, the Atherosclerosis Risk in Communities (ARIC) Study, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are associated positively with incidence of stroke. We measured plasma high-sensitivity TnT and NT-proBNP in 10,902 men or women initially free of stroke and followed them for a mean of 11.3 years for stroke occurrence (n=507). Analyses were performed using proportional hazards modeling. Both biomarkers were associated positively with total stroke, nonlacunar ischemic, and especially, cardioembolic stroke, but not with lacunar or hemorrhagic stroke. After adjustment for other stroke risk factors, the hazard ratio (95% CI) per one SD greater increment of natural log-transformed TnT was 1.23 (1.13, 1.35) for total stroke, 1.27 (1.15, 1.40) for total ischemic stroke, and 1.36 (1.14, 1.62) for cardioembolic stroke. Likewise, the hazard ratio per one SD greater natural log-transformed NT-proBNP, was 1.37 (1.26, 1.49) for total stroke, 1.39 (1.27, 1.53) for total ischemic stroke, and 1.95 (1.67, 2.28) for cardioembolic stroke. The hazard ratios for jointly high values of TnT (≥0.013 ug/L) and NT-proBNP (≥155.2 pg/mL), versus neither biomarker high, were 2.70 (1.92, 3.79) for total stroke and 6.26 (3.40, 11.5) for cardioembolic stroke, and somewhat stronger for NT-proBNP than TnT. Strikingly, approximately 58% of cardioembolic strokes occurred in the highest quintile of pre-stroke NT-proBNP (versus 3% occurring in the lowest quintile), and 32% of cardioembolic strokes occurred in participants who had both NT-proBNP in the highest quintile and were known by ARIC to have atrial fibrillation sometime before their cardioembolic stroke occurrence. In conclusion, in the general population, elevated plasma TnT and NT-proBNP concentrations are associated with increased risk of cardioembolic and other nonlacunar ischemic strokes.
Abstract 82: Serum VEGF Levels Alter Risk of Stroke: the Framingham Heart Study
Authors: Pikula Aleksandra , Beiser Alexa S , Chen Tai C , Preis Sarah R , Vorgias Demetrios , Au Rhoda , Kelly-Hayes Margaret , Kase Carlos S , Wolf Philip A , Vasan Ramachandran S , Seshadri Sudha
Published: July 2021

Objective:
To examine the association of serum VEGF levels with incident stroke and transient ischemic attack (TIA) in a large, community-based cohort.

Background:
VEGF, an endothelial growth factor promotes angiogenesis and neurogenesis and has demonstrated neuroprotective properties in animal experiments. However, high circulating VEGF levels have also been observed in patients with vascular risk factors, atherosclerosis and in small studies of acute stroke. There have been no studies examining the association of serum VEGF with the risk of stroke in a community-based sample.

Methods:
In 3440 stroke/TIA-free FHS participants (mean age 65+11yrs, 56%W), we related baseline VEGF (log-transformed) to risk of incident stroke/TIA. To examine the incremental utility of VEGF over age-, sex- and baseline Framingham Stroke Risk Profile (FSRP) in predicting stroke/TIA, we also calculated the net reclassification improvement (NRI).

Results:
During a median follow-up of 10 years, 193 participants experienced incident stroke/TIA (129 ischemic strokes). In multivariable analyses adjusted for age-, sex- and traditional stroke risk factors (as identified by the FSRP), higher logVEGF levels were associated with an increased risk of incident stroke/TIA (HR/1SD increase in logVEGF: 1.21, 95%CI: 1.04-1.40, p=0.012). This was also true for incident ischemic stroke events (HR/1SD increase in logVEGF: 1.21 95%CI: 1.01-1.44 p=0.04). In reclassification analyses, logVEGF, when added to a risk assessment model based on the FSRP resulted in significant improvement of risk prediction with NRI of 0.046 (p=0.036).

Interpretation:
After adjusting for traditional stroke risk factors, higher VEGF concentrations were associated with increased risk of incident stroke/TIA, suggesting that VEGF may serve as a novel risk marker for stroke/TIA and to improve risk stratification permitting more targeted preventive interventions.
Abstract 84: The Effect of Hyperglycemia on Stroke Outcome Depends on Baseline Glycosylated Hemoglobin Levels
Authors: Park Kwang-Yeol , Helenius Johanna , Avery Ross , Kim Gyeong-Moon , Buonanno Ferdinando S , Ay Hakan
Published: July 2021

Background and hypothesis:
Patients with diabetes mellitus (DM) are less likely to develop adverse outcomes than are those without DM in response to acute elevations in plasma glucose after stroke. We hypothesized that baseline glycosylated hemoglobin (HbA1c) level, which provides an estimate of long-term plasma glucose concentration, inversely correlated with clinical and tissue outcome in acute ischemic stroke patients presenting with hyperglycemia.

Methods:
Within the context of an ongoing prospective study (Heart-Brain Interactions Study), we measured plasma glucose and HbA1c levels in 1080 patients with acute ischemic stroke within 72 hours of symptom onset. We classified patients into 3 HbA1c strata based on the American Diabetes Association criteria: group-I (HbA1c <5.7%, n=439), group-II (HbA1c: 5.7 to 6.4%, n=290), group-III (known DM or HbA1c >6.4, n=351). We examined the relationship between admission blood glucose level, acute infarct volume on DWI, and unfavorable outcome (mRS≥3) at 3 months in each HbA1c stratum.

Results:
The probability of unfavorable outcome decreased by increasing baseline HbA1c level; the OR (95% CI) for unfavorable outcome for every 10 mg/dl increase in glucose level was 1.42 (1.25-1.62) in group-I, 1.19 (1.07-1.33) in group-II, and 1.02 (0.99-1.05) in group-III. When hyperglycemia was defined as ≥144 mg/dl, OR (95% CI) for unfavorable outcome was 6.53 (2.65-16.14) in group-I, 1.56 (0.77-3.15) in group-II, and 1.35 (0.78-2.33) in group-III. Adjusting for age and sex did not change the results. For every 10 ml elevation in plasma glucose, the mean infarct volume increased by 7.45 ml (5.04-9.85) in group-I, 4.96 ml (2.82-7.09) in group-II, and 0.73 ml (-0.24-1.70) in group-III.

Conclusions:
Chronic hyperglycemia appears to protect from deleterious effects of acute elevations in blood glucose after ischemic stroke. Further research is warranted examining whether baseline HbA1c concentration predicts benefit from interventions for glycemic control in acute stroke.
Abstract 85: Human Neuronal Cells Directly Induced From Human Skin Fibroblasts: A Novel Cell Resource For Stroke Therapy
Authors: Yamashita Toru , Abeliovich Asa , Abe Koji
Published: July 2021

Strokes induce tremendous neuronal death, are a major cause of death and reduce the quality of life. Induced pluripotent stem cell methods, which supply neuronal cells, may provide cures for various neurological diseases including stroke, although their tumorigenicity interferes with clinical applications. To induce neuronal cells without passing the pluripotent state, we tried to convert human skin fibroblasts to human-induced neuronal (hiN) cells by viral cotransduction of a combination of five neuron specific transcription factors, Ascl1, Brn2, Myt1l, Olig2, and Zic1. Three weeks after viral transduction, we found these hiN cells were positive for neuronal markers, including Tuj1, MAP2, Tau1, and NeuN, and showed a neuronal morphology. We also confirmed that the hiN cell phenotype can be achieved without expression of the progenitor/stem cell markers Sox2, Pax6, Otx2, or FoxG1 during hiN cell reprogramming. Of note, we demonstrated that GFP-labeled hiN cells, which were transplanted
in utero
into an embryonic day 13.5 mouse brain, could migrate from the ventricles into various brain regions. Moreover, the results of voltage-clamp recordings from hiN cells within acutely prepared brain slices indicated that hiN cells can make functional neuronal connections with the surrounding neuronal circuit
in vivo
. Taken together, these results suggest that this novel hiN method can supply functional neuronal cells from human skin fibroblasts without passing through the progenitor/pluripotent state. Here, we propose that hiN cells can be a promising cell source for cell transplantation therapy to stroke patients.
Abstract TMP110: Arterial Stiffness And Progressive Neurological Deficit In Patients With Acute Deep Subcortical Infarction
Authors: Saji Naoki , Kimura Kazumi , Kawarai Toshitaka , Shimizu Hirotaka , Kita Yasushi
Published: July 2021

Introduction:
Deep subcortical infarction sometimes presents with progressive neurological deficit (PND). The etiology of PND is the occlusion of perforating arteries due to cerebral small vessel disease. Cerebral small vessel disease is associated with arterial stiffness, a marker of both arteriosclerosis and vascular endothelial impairment, and can cause neurological damage.

Hypothesis:
Arterial stiffness is independently associated with PND in patients with acute deep subcortical infarcts.

Methods:
Between October 2003 and March 2010, we evaluated 156 consecutive first-ever ischemic stroke patients with acute deep subcortical infarction. PND was defined as an increment of ≥2 points in the National Institute of Health Stroke Scale score or an increase of ≥1 point in the limb weakness score within seven days of stroke onset. Patients were assessed for risk factors, and infarct size was measured on initial diffusion-weighted magnetic resonance imaging (DWI). We measured brachial-ankle pulse wave velocity (baPWV) as a marker of arterial stiffness using an oscillometric device (Form PWV/ABI®; Omron Colin Co., Ltd., Tokyo, Japan). We divided patients into two groups according to the presence or absence of PND to compare their clinical characteristics.

Results:
Fifty-two patients (33%) had PND, and baPWV was significantly higher in patients with than without PND. The baPWV cutoff value for PND was 18.24 m/s, with 90% sensitivity and 47% specificity. In multivariable logistic regression analysis, high baPWV [≥18.24 m/s, odds ratio (OR) 8.22, 95% confidence interval (95% CI) 2.55-31.9], large infarct size (≥15 mm, OR 2.76, 95% CI 1.01-7.92) and ≥3 infarct slices on serial axial DWI (OR 3.38, 95% CI 1.22-10.0) were independently associated with PND.

Conclusions:
Arterial stiffness indicated by baPWV is independently associated with PND in patients with acute deep subcortical infarction.
Abstract TMP15: Contralateral Hemispheric Atrophy After Major Hemispheric Infarction
Authors: Barnett Austin A , Selman Warren , Sila Cathy
Published: July 2021

Objective:
Atrophy of the ipsilateral hemisphere, cerebral peduncle, and contralateral cerebellum predict outcome after stroke; little is known of the effect of stroke on the contralateral hemisphere although it plays an important role in functional reorganization.

Methods:
All patients who underwent decompressive hemicraniectomy for malignant hemispheric infarction at UH-CMC between 1/2003-12/2009 were analyzed with IRB approval. Patients with adequate CT scans both prior to surgery and after reconstructive cranioplasty were included; those with communicating hydrocephalus, confounding lesions or ≥ 10 mm of midline shift were excluded. Brainlab iPlan® software (Germany) was used to manually trace the infarct, non-infarct ipsilateral and contralateral hemisphere on axial, sagittal and coronal slices.

Results:
Of 30 patients, 9 met inclusion criteria. The inter-rater reliability of volumetric analyses was excellent (r=0.99). The mean contralateral hemisphere volume at follow-up was significantly reduced compared to the baseline study (465.987 ± 78.32 cc vs 493.429 ±76.92 cc, p< 0.0001,
Fisher’s two-tailed t-test
). Contralateral hemispheric atrophy was identified in all patients (mean 27.441 cc, range 4.985 - 42.807 cc) and represented a loss of 5.7% (1.2 - 11.16%) of the original volume. Contralateral hemispheric atrophy was significantly related to the volume of the infarct and the time from stroke onset to decompressive hemicraniectomy but not to the extent of midline shift on the post-operative scan nor <10 mm on the pre-operative scan. Contralateral hemispheral atrophy was identified early and not related to the length of follow-up (median 4.5, range 2-43 months).

Conclusions:
Contralateral hemispheric atrophy occurs within months of major hemispheral infarction and is related to infarct size and the time to decompressive hemicraniectomy.
Abstract TMP28: Aspirin Attenuates Inflmmation in the Wall of Human Cerebral Aneurysms
Authors: Hasan David M
Published: July 2021

Background:
Inflammatory cells and molecules play a critical role in formation and rupture of cerebral aneurysms. Recently, an epidemiologic study reported that aspirin decreases the risk of aneurysm rupture. The goal of this study was to determine effects of aspirin on inflammatory cells and molecules in the wall of human cerebral aneurysms, using radiographic and histological techniques.

Methods:
Ten prospectively enrolled patients harboring 11 unruptured intracranial aneurysms were randomized into
aspirin
-treated (81 mg daily) and untreated (control)
groups.
Aneurysms were imaged at baseline using ferumoxytol-enhanced MRI to estimate uptake by macrophages. After three months, all 10 patients were re-imaged before undergoing microsurgical clipping. Aneurysm tissues were collected for immunostaining with monoclonal antibodies for cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal prostaglandin E2 synthase-1 (mPGES-1) and macrophages.

Results:
A decrease in signal intensity on ferumoxytol-enhanced MRI was observed after three months of aspirin treatment. Expression of COX-2 (but not COX-1), mPGES-1, and macrophages was lower in the aspirin group than the control group.

Conclusion:
This study provides radiographic and histological evidence that aspirin attenuates the inflammatory process in the wall of human cerebral aneurysms.
Abstract TMP47: Risk Factors for Intracerebral Hemorrhage and the Racial Differences in the Impact of Age on Risk: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Howard George , Cushman Mary , Howard Virginia J , Judd Suzanne E , Kissela Brett M , Kleindorfer Dawn O , Moy Claudia S , Rhodes David J , Switzer Jeffrey A , Woo Daniel
Published: July 2021

Introduction:
Because of low incidence rates, risk factors for intracerebral hemorrhage (ICH) have largely been estimated in case/control studies, very selected population cohorts, or by pooling of multiple longitudinal cohorts.

Methods:
REGARDS is a longitudinal cohort study of 30,239 African American (AA) and white community-dwelling participants aged 45 and over, recruited from the 48 contiguous US states. Physician-adjudicated incident stroke events in the REGARDS study were used to assess risk factors for ICH among those stroke-free at baseline.

Results:
A total of 62 ICH events occurred over an average 5.6 year follow-up among 27,760 participants stroke-free at baseline. In multivariable models, there was a significant (p = 0.0066) interaction between race and age; ICH risk dramatically increases with age for whites (HR = 2.03 per 10 year difference; 95% CI: 1.14 - 2.86), but there was little evidence of increasing risk with age in AAs (HR = 1.01 per 10 year difference; 95%: 0.65 - 1.58). This differential impact of age underlies a substantial excess in AA-to-white risk at age 45 (HR = 5.30; 95% CI: 1.41 - 19.91), but a marginally lower risk at age 85 (HR = 0.33; 95% CI: 0.10 - 1.05) (see figure). Risk of ICH was also significantly higher for men than women (HR = 2.60; 95% CI: 1.50 - 4.48), in those with higher systolic blood pressure (HR = 1.19 per 10 mmHg difference; 95% CI: 1.05 - 1.36), and for warfarin use to non-use (HR = 2.24; 95% CI: 1.01 - 5.00). Diabetes, chronic kidney disease, cholesterol components, smoking, alcohol use, and aspirin use were not related to ICH risk.

Discussion:
Additional research is needed to understand the striking AA-to-white differences in ICH risk across the age spectrum. In addition, higher systolic blood pressure, male sex, and warfarin were confirmed as substantial ICH risk factors in the general population. Other factors found to be significant in other studies were not confirmed in this single cohort, population-based, longitudinal cohort study.
Abstract TMP83: Propensity Score Matching to Estimate Supported Outcomes in Intracerebral Hemorrhage Patients with Withdrawal of Life Support
Authors: Tirschwell David L , Becker Kyra J , Creutzfeldt Claire J , Gallo Marisa , Longstreth W. T
Published: July 2021

Background:
Observational reports suggest that a self-fulfilling prognostic pessimism may lead to withdrawal of life support (WOLS) in patients with more severe intracerebral hemorrhages (ICHs) who might otherwise have acceptable clinical outcomes. Our objective was to estimate what outcomes in a cohort of ICH patients might have been if they did not have WOLS.

Methods:
Multivariate modeling was used to create a propensity score (PS) for WOLS in a Seattle single center cohort of ICH patients with hospital discharge modified Rankin Scale (mRS) as the primary outcome. Using nearest neighbor matching, individual ICH patients with WOLS were matched to individual ICH patients without WOLS and baseline variables and outcome were compared.

Results:
The cohort comprised 590 ICH patients with mean age of 67 years, 42% women, 76% white and 18% WOLS. Factors used to create the PS for WOLS included age, pre-ICH mRS, GCS, ICH volume, intraventricular hemorrhage, pre-existing hypertension, diabetes and atrial fibrillation, first temperature and intubation. Matches were possible for 78 WOLS/non-WOLS pairs. Groups were well matched on all PS factors, mean age (67 years), GCS (6.4), ICH volume (59cc) and % intubation (59). Discharge mRS in the both groups varied from 3-6 and was for the WOLS group 1.3%, 2.6%, 6.4% and 90% respectively; in the matched non-WOLS group discharge mRS was 6.4%, 32%, 24% and 37% respectively (difference p<0.0005). Using mRS <= 4 at discharge as an acceptable outcome, % in WOLS/non-WOLS were 4%/38% (difference p<0.0005).

Conclusions:
The proportion of ICH patients with WOLS that might have had an acceptable outcome without WOLS was ~38%. This discharge “acceptable outcome” of mRS <= 4 assumes eventual recovery to better function in many. The 34% absolute difference in WOLS/non-WOLS outcomes suggests that for every 3 fewer ICH patients with WOLS, one more patient might have an acceptable clinical outcome. This proportion would vary depending on an individual patient’s interpretation of what constitutes an acceptable outcome.
Abstract TMP88: Slipping, Tripping, and Rapid Ambulation are Key Fall Triggers for Stroke Survivors
Authors: Hoke Tiffany M , Taylor-Piliae Ruth E
Published: July 2021

Background:
Stroke survivors fall up to seven times more annually than healthy adults of a similar age. The inability to recover balance from slipping, tripping, or rapid ambulation accounts for the majority of falls, while balance control can prevent falls. An examination of the triggers for falls and balance recovery strategies for near falls is crucial for fall prevention in stroke survivors.

Purpose:
To examine the self-reported triggers for falls and balance recovery strategies for near falls among community-dwelling stroke survivors.

Methods:
Descriptive study examining fall-related data from stroke survivors (n=89) aged ≥ 50 years, at ≥ 3 months post-stroke, participating in a 12-week exercise intervention study. All subjects were interviewed weekly to ascertain fall/near fall data over the 12 weeks. Falls were defined as: “events in which subjects end up on the floor or ground when they did not expect to.” Near falls were defined as: “events in which subjects recovered their balance without falling.”

Results:
Subjects (46% women) were on average 70±10 years old. The majority reported an ischemic stroke (80%), were White/European-American (79%), married/partnered (60%), college-educated (79%), and retired/unemployed (93%). Over the 12-week trial, there were a total of 124 fall-related events (n=34 falls, n=90 near falls); all events happened at home. Most falls happened due to slipping or tripping (21%) or rapid ambulation (18%). Other reported fall triggers included: legs or knees giving way (12%), bathroom related incidents such as incontinence (12%), reaching or leaning (6%), and vertigo or syncope (3%). Subjects most commonly recovered their balance without falling by grabbing onto or leaning against something (62%). A total of 29 (23%) fall-related events resulted in an injury, though only 8% of those events were evaluated by a healthcare provider.

Conclusion:
Our data suggests that stroke survivors fall most frequently as a result of slipping, tripping or rapid ambulation. Future studies investigating the effects of fall prevention strategies on these fall triggers are recommended. Since balance recovery was aided by grabbing onto or leaning against something, post-stroke home safety evaluation is essential in preventing falls.