bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 119: Risk of Intracerebral Hemorrhage with Combined Antiplatelet and Anticoagulant Use
Authors: Flaherty Matthew L , Ding Lili , Woo Jessica G , Martin Lisa , Haverbusch Mary , Moomaw Charles J , Martini Sharyl , Adeoye Opeolu , Broderick Joseph P , Woo Daniel
Published: July 2021

Context:
Intracranial bleeding is the most feared complication of antithrombotic use. Antiplatelet and anticoagulant drugs increase risk of intracerebral hemorrhage (ICH), yet in some instances, combinations of antiplatelet agents and anticoagulants are used without firm evidence of efficacy. Few studies have compared the risks of different agents and their combinations in a single population. We determined the risk of ICH associated with the most commonly used antiplatelet and anticoagulant drugs and their combinations in a population-based case-control study.

Methods:
This report includes data from subjects recruited from the Greater Cincinnati/Northern Kentucky area by the Genetic and Environmental Risk Factors for Hemorrhagic Stroke Study from 1997 to 2009. We compared individuals in different treatment groups to identify any differences in baseline covariates that could be associated with treatment assignment. As there were a number of statistically significant differences, we used multivariate matching to analyze risk for ICH conferred by different antithrombotic agents. Treatment effects on ICH were estimated using the matched samples while accounting for the dependence between matched individuals.

Results:
There were 733 subjects with ICH and 2555 controls included in this study period. Results are shown in the table. Use of aspirin, clopidogrel, or their combination was associated with a trend toward increased risk. Warfarin increased risk compared with no antithrombotic use (OR 3.98, p < 0.0001). The combination of warfarin and either aspirin or clopidogrel produced the greatest risk, compared with no antithrombic therapy (OR 4.92 p<0.001) or compared with warfarin alone (OR 3.00 p=0.009).

Conclusions:
The combination of warfarin and an antiplatelet drug significantly increases risk of ICH compared with no antithrombotic therapy or warfarin monotherapy. The use of combination therapy requires careful consideration in clinical practice.
Abstract 120: Predictive Validity of Barthel Index Compared to NIHSS for Discharge Destination Following an Acute Stroke Hospitalization
Authors: Prvu Bettger Janet , Magdon-Ismail Zainab , Hedeman Robin , Sicklick Alyse , Schwamm Lee , Stein Joel
Published: July 2021

Introduction:
Clinical practice guidelines recommend all stroke patients receive a brief functional assessment to help determine need for rehabilitation services. However, the value of a standardized functional assessment for determining rehabilitation service need is unclear. This study evaluated the predictive validity of the Barthel Index (BI) compared to admission NIHSS for predicting discharge to institution-based rehabilitation vs. home, and discharge to inpatient rehabilitation (IRF) vs. skilled nursing facilities (SNF).

Methods:
We analyzed data from a Northeast Cerebrovascular Consortium feasibility study of 22 Get With The Guidelines-Stroke participating hospitals that completed a standardized assessment including NIHSS and BI. Patients with TIA or who died in hospital, left AMA, or were discharged to another acute hospital or hospice were excluded. Multivariable logistic regression was used to examine BI scores (in quintiles) with discharge to institution-based rehabilitation (IRF or SNF) vs. home, and discharge to IRF vs. SNF. Models were repeated for NIHSS in place of the BI.

Results:
Among the 792 eligible stroke patients, mean age was 69±15 years, 51% were female, 54% had Medicare insurance, 89% had an ischemic stroke, and 61% were independent pre-stroke (modified Rankin scale score=0-1). After accounting for these factors, the highest two BI quintiles (85-100 and 65-80 compared to 0-20=severely impaired) were independently associated with discharge to institution-based rehabilitation compared to home (OR=0.01, 95%CI=0.003-0.02 and OR=0.06, 95%CI=0.03-0.14, respectively) and explained 90.2% of the variance. NIHSS score was also associated with discharge to institution-based rehabilitation (OR=0.18, 95% CI 1.14-1.23) and the model explained 82.3% of the variance. BI was not associated with discharge to SNF vs. IRF (p>0.1, c=0.763) and NIHSS was (OR=1.06, 95%CI=1.02-1.11, c=0.80) after accounting for patient-level factors.

Discussion:
The predictive validity of BI was better than NIHSS for discharge to institution-based rehabilitation compared to home. NIHSS but not the BI predicted discharge to SNF vs. IRF. Research is needed to help direct survivors to the appropriate level--IRF or SNF--rehabilitation care.
Abstract 125: Repetitive Transcranial Magnetic Stimulation Once A Week Induces Sustainable Long-term Relief Of Post-stroke Pain
Authors: Kobayashi Masahito , Fujimaki Takamitsu , Mihara Ban
Published: July 2021

Introduction:
Post-stroke thalamic pain is a serious problem for some patients after stroke, deteriorating their activities of daily life, and is often resistant to medical treatments. Surgical intervention, such as electrical motor cortex stimulation, has been reported to be effective, but only for 40-60% of the patients despite of invasive procedures and costly devices. For some patients with electrical motor cortex stimulation, continuous stimulation is not always essential while occasional stimulation, such as a few hours every several days, is enough for their pain control. Recently, repetitive transcranial magnetic stimulation (rTMS) is reported to relieve post-stroke pain transiently but effectively.

Hypothesis:
We assessed the hypothesis that rTMS of motor cortex, maintained once a week, could induce sustainable long-term pain relief in patients with medication-resistant post-stroke pain.

Methods:
Fifteen patients suffering from medication-resistant post-stroke pain after thalamic hemorrhagic stroke were included. rTMS (10 trains of 10-second 5Hz TMS pulses at 50-second intervals, 90% of active motor threshold) was delivered on the motor cortex of the affected side. The rTMS session was repeated once a week for more than 12 weeks. The effect of rTMS on pain was rated by patients using a visual analog scale (VAS).

Result:
Mean VAS (±SEM) before rTMS (baseline) was 6.4±0.4 and reduced gradually and significantly in accordance with rTMS sessions. The VAS 12 weeks later was 3.4±0.5. Nine of 15 patients (60%) reported reduction of three or more VAS points. Five patients suffering from paresthesia rather than pain showed less reduction of VAS compared to the others. In five patients, rTMS was continued for one year and the effect of pain relief was also sustained.

Conclusion:
rTMS of the motor cortex, when maintained once a week, can provide long-term pain relief in patients with medication-resistant post-stroke pain.
Abstract 130: SWIFT! Early Presentation is Associated with Better Collaterals, Smaller Established Infarcts, and Better Clinical Outcomes from Endovascular Recanalization
Authors: Liebeskind David S , Jahan Reza , Nogueira Raul G , Jovin Tudor G , Lutsep Helmi L , Saver Jeffrey L ,   for the SWIFT Investigators
Published: July 2021

Background:
Increasing time from symptom onset to presentation may incur greater ischemic injury and decreased likelihood of successful outcomes after acute stroke therapy. The impact of time may be assessed physiologically by degree of accumulated ischemic injury on baseline imaging and status of collateral vessels at angiography; and clinically by final functional outcome.

Methods:
The SWIFT trial dataset was analyzed with respect to ASPECTS scores, angiographic collaterals, clinical outcome, and time to presentation (defined as stroke onset to hospital arrival). Known determinants of successful angiographic and clinical outcomes were considered as covariates, with main analyses defining the interaction of time to presentation on ASPECTS score, collateral grade, reperfusion and related clinical outcome.

Results:
137 patients (mean age 67±12 years, 52% female, median pretreatment NIHSS 18 (range 8-28)) with full data were studied. Time to presentation was median 180 min (IQR 95-250) and was < 3 hours in 51% and > 3 hours in 49%. Time to presentation was unrelated to age, gender, most risk factors (except atrial fibrillation (present < 3 hours in 41.4% vs. > 3 hours in 64.2%, p=0.010), NIHSS, glucose or BP. Pre-stroke mRS 0, however, was associated with presentation < 3 hours, (82.8% vs. 63.8%, p=0.035). Worse collateral scores were noted with longer times to presentation: collateral grade 0-1 (n=32) mean 232±84 min; 2 (n=48) 164±99 min; 3 (n=35) 155±104 min; 4 (n=4) 54±16 min; p<0.001. Later presentation was associated with more extensive ischemic injury at baseline (median ASPECTS 8 (IQR 7-9) beyond 3 hours vs. 9 (IQR 8-10) within 3 hours, p=0.015). Multivariate analyses identified presentation > 3 hours as the sole independent predictor of extensive baseline infarct (ASPECTS ≤ 7), p=0.003. Time to presentation was unrelated with likelihood of successful angiographic reperfusion (p=NS), yet earlier presentation demonstrated a strong influence with better Day 90 mRS outcomes (p<0.001).

Conclusions:
Time was a critical factor in successful clinical outcomes in SWIFT. Shorter times to presentation were associated with better collaterals, smaller established infarcts and better clinical outcome after revascularization.
Abstract 132: The Canadian TIA Rule - A Decision Rule to Predict the Risk Of Stroke Within Seven Days In The Emergency Department
Authors: Perry Jeffrey , Sharma Mukul , Sivilotti Marco L , Sutherland Jane , Symington Cheryl , Emond Marcel , Worster Andrew , Grant Stotts , Wells George A , Stiell Ian G
Published: July 2021

Background:
Stroke prevention after TIA is dependent on rapid intervention in those at highest risk. Previous risk scores have not been prospectively developed and thus do not consider all relevant variables. The goal of this study was to derive a clinical score for TIA patients to identify those at high risk for stroke ≤ 7 days.

Methods:
We conducted a prospective cohort study in 8 academic Canadian EDs. We enrolled consecutive adult ED patients diagnosed with a TIA. Standardized clinical variables were recorded by physicians on data forms prior to discharge/admission. Our
primary outcome was
stroke ≤ 7 days of TIA diagnosis. We derived a clinical score using logistic regression analysis.

Results:
We prospectively enrolled 3,903 patients including 85 patients with a subsequent stroke ≤ 7 days. From this cohort we derived the
Canadian TIA Score
. The Canadian TIA Score identifies patients at minimal risk of subsequent stroke ≤ 7 days (probability < 0.5%), low risk (0.5-2.5%), high risk (2.6-10.0%), and critical risk (>10.0%). This score contains 13 variables; 9
clincal:
1) initial TIA (in lifetime) 2) symptoms lasting ≥10 minutes, 3) already on an antiplatelet agent, 4) history of carotid stensosis, 5) history of gait disturbance, 6) unilateral weakness, 7) vertigo, 8) initial diastolic blood pressure ≥110 mmHg, 9) history or exam finding of dysarthria or aphasia; and four from
investigations:
1) atrial fibrillation on electrocardiogram, 2) infarction on CT head, 3) platelets ≥400 x 10
9
/L, 4) glucose ≥15 mmol/L. Variables were assigned point values ranging from 4 to -3, and added, obtaining a score from -3 to 19. This model has good discrimination with a c-statistic of 0.77 (95%CI: 0.73-0.82).

Importance:
The Canadian TIA Score identifies the subsequent stroke risk at 7 days following a TIA. Following validation, the Canadian TIA Score will allow physicians to selectively expedite investigations/specialist assessment and allow for safe less urgent follow-up of patients at low risk. Appropriate intervention is contingent on appropriate risk assessment.
Abstract 137: The Effect Of Mitophagy During Transient Ischemic Brain In Rats
Authors: Li Qiang , Zhang Ting , Wang Jixian , Wang Yongting , Yang Guo-Yuan , Sun Xiaojiang
Published: July 2021

Background and Purpose:
Mitochondria provides energy to maintain normal cell functioning. Mitophagy is one of mitochondria functions, which can clear out injured mitochondria, ensure stability of mitochondria and promote cell survival in hostile environment. However, if mitophagy occurs during cerebral ischemia is unknown. The present study explored dynamic mitophagy, the effect of promoting mitophagy, and the molecular mechanisms of mitophagy during cerebral ischemia/reperfusion.

Methods:
Adult male SD rats underwent 2h middle cerebral artery occlusion (MCAO) followed by 6 to 72h reperfusion. Dynamic changes of mitophagy were determined by LC3 immunostaining, Western blot analysis, and transmission electron microscope. To study the impact of mitophagy, we injected rapamycin, a mitophagy stimulator, into the left ventricle in rats underwent transient MCAO. To evaluate the effect of mitophagy, neuronal death and neurological deficits were determined. To explore the effect of mitophagy on mitochondria function, the number of mitochondria, the levels of MDA, ATP, and JC-1 were examined. To study the mechanism of mitophagy, mitochondrial Beclin-1 and p62 expression were also determined.

Results:
We demonstrated that autophagy was mainly detected in mitochondria in the peri-focal area of ischemic cortex after ischemia/reperfusion. Mitophagy was increased at 6h (p<0.05), peaked at 24h (p<0.05), gradually reduced at 48h (p<0.05), and returned to normal at 72h of transient MCAO. Pre-treatment with rapamycin greatly enhanced mitophagy, reduced infarct volume, and improved neurological outcomes compared to the control (p<0.05). We found that the number of mitochondria and mtDNA copy, mitochondria ATP synthesis level, and JC-1 were increased (p<0.05), and MDA was reduced in rapamycin treated rats (p<0.05). We further demonstrated that rapamycin pre-treatment enhanced mitochondrial Beclin-1and p62 in mitochondria.

Conclusion:
We demonstrated ischemia could induce mitophagy in brain cells. Rapamycin attenuated ischemic brain injury, which was via stimulating mitophagy that can reduce oxidative stress and improve mitochondria function. The mechanism of rapamycin promoting mitophagy was through increasing Beclin-1 and p62 expression.
Abstract 138: Gamma Delta TCR Lymphocytes and Immune Memory of Ischemic Stroke
Authors: Adamski Mateusz G , Wagner Erin , Li Yan , Yu Hua , Seales-Bailey Chloe , Soper Steven A , Murphy Michael A , Baird Alison E
Published: July 2021

Background:
Inflammation plays an important role in ischemic stroke (IS) pathophysiology. Gamma/delta+ TCR (gdTCR), CD8+gdTCR, and CD4+ gdTCR lymphocytes are newly recognized contributors to innate immune systems responses. In experimental stroke models gdTCR lymphocytes have been found to contribute substantially to cerebral infarct growth and have the potential to contribute to immune memory after stroke. We aimed to determine whether changes in gdTCR cellular count and lymphocyte activity occur after human stroke, and if differences exist between first-ever and recurrent IS.

Methods:
First-ever IS patients (n=20), recurrent IS patients (n=29) and matched healthy control subjects (n=28) were studied. Blood was drawn within 72 hours of stroke onset and was stained with CD3 (PE-TR), gdTCR (PE), CD4 (FITC) and CD8 (PE-Cy5) monoclonal antibodies. The percentages of circulating gdTCR lymphocytes were evaluated by fluorescent-activated cell counter and analyzed using “FlowJo” software. The expression of selected inflammatory and stroke-related genes, based on previous reports, was measured in gdTCR lymphocytes isolated from 7 first-ever IS patients and 14 recurrent IS patients. Magnetic bead separation was used for cellular isolation and messenger ribonucleic acid expression was measured using digital polymerase chain reactions. Statistical analyses used Mann-Whitney U tests and chi-square tests.

Results:
The numbers of CD8+gdTCR cells were higher in all IS patients vs. control subjects (p=.04) and in recurrent IS patients vs. control subjects (p=.01). No difference was seen between first ever IS patients and control subjects (p=.4). Comparison of gdTCR cellular gene expression between recurrent IS patients and first-ever IS patients showed significantly higher expression of MMP9 (p=.02) and SLC2A3 (p=.04) in recurrent IS patients. TLR2 and IL23R were also borderline significantly higher in recurrent IS patients (0.05<p<0.1). No differences in gdTCR or CD4+ gdTCR counts were found between IS patients and controls.

Conclusion:
Alterations in gdTCR gene expression and in levels of the CD8+TCR subset in patients with recurrent stroke may indicate a potential role of the innate system in immune memory after ischemic stroke.
Abstract 147: Cannabis, Ischemic Stroke and Transient Ischemic Attack: A Case Control Study
Authors: Barber P A , Pridmore Heidi , Krishnamurthy Venkatesh , Roberts Sally , Spriggs David A , Carter Kristie , Anderson Neil E
Published: July 2021

Background:
Cannabis is the most widely used illicit drug of abuse. A temporal relationship between cannabis use and stroke has been reported in case series and population based studies. To date this relationship has not been confirmed. We performed a case-controlled study on the recent use of cannabis in younger stroke patients.

Methods:
Consecutive ischemic stroke/TIA patients aged 18-55 years had urine screens for cannabis. A control cohort of age, sex and ethnicity matched hospital patients were screened for cannabis using anonymized urine samples obtained for other indications and which would otherwise be discarded. The study was performed with the approval of the regional Ethics Committee.

Results:
One hundred and sixty of 218 (73%) ischemic stroke/TIA patients had urine drug screens [100 men, 60 women; mean (SD) age 44.8 (8.7) years], of whom 150 (94%) had ischemic stroke and 10 (6%) had TIA. Fifty-eight patients did not have drug screens, mainly because they were admitted outside office hours or had been discharged early (primarily TIA patients). All of the patients approached to provide a urine sample agreed to do so. Twenty-five (15.6%) patients had positive cannabis drug screens, and these patients were more likely to be male (84% versus 59%, χ
2
p=0.016) and tobacco smokers (88% versus 28%, χ
2
p<0.001). There were no differences in age, stroke mechanism or most vascular risk factors between those with and without positive cannabis tests. Control urine samples were obtained from 160 patients matched for age (t-test, p=0.979), sex (χ
2
p=0.492) and ethnicity (χ
2
p=0.910). Thirteen (8.1%) control participants tested positive for cannabis. In a logistic regression analysis adjusted for age, sex and ethnicity, cannabis use was associated with increased risk of ischemic stroke and TIA (odds ratio 2.30, 95% confidence intervals 1.07-4.95).

Conclusions:
This study provides the strongest evidence to date of an association between cannabis and stroke, with ischemic stroke and TIA patients twice as to have recently used cannabis likely as control participants. Cannabis is generally perceived as having few serious adverse effects. This study suggests that this may not be the case and that the association between cannabis and stroke warrants further investigation.
Abstract 151: The Effects of Obstructive Sleep Apnea on the Cerebral Vascular Wall
Authors: Bryan Robert M , Crossland Randy F , Durgan David J
Published: July 2021

Obstructive sleep apnea (OSA) is a significant risk factor for stroke. However, little is known regarding how OSA affects the cerebrovascular wall. We hypothesized that (A) OSA will attenuate dilations of cerebral arteries by agonist-induced NO release from cerebrovascular endothelium and (B) OSA will upregulate endothelin-1 (ET-1)-mediated constrictions in cerebral arteries. Airway obstructions were induced by chronically implanting inflatable endotracheal obstruction devices (ODs). The ODs were remotely controlled by a computer to produce 30 apneas/hr (10 sec each) during 8 hrs of the sleep cycle in free-ranging rats. During apnea pO
2
decreased from 122±3 to 67±3 mm Hg; pCO
2
increased from 43±1 to 51±1 mm Hg; pH decreased from 7.46±0.00 to 7.38±0.01; and hemoglobin O
2
saturation decreased from 94±1 to 82±1 % (n=5 and p<0.003 for each). After 4 weeks of apnea blood pressure in OSA rats were similar to that in sham rats (108±1 and 103±1 mmHg respectively). Cerebral arteries were isolated after 4 weeks from sham and OSA rats, mounted on pipettes, and pressurized. Diameter changes of the cerebral arteries were measured after the addition of various agents. Dilations to ATP, a P2Y
2
agonist which stimulates NO production in the endothelium, were attenuated in cerebral arteries from OSA rats by 40% (n=5-8, P<0.05). However, the dilations to the NO donor, MAHMA-NOnoate, were similar between groups. Sensitivity to ET-1, an agonist for ET
A
and ET
B
, was increased ~20 fold in OSA arteries. EC
50
s for ET-1 constrictions in cerebral arteries from sham and OSA rats were 10.7 ± 4.3 nM and 0.5 ± 0.4 nM respectively (n=5-6, p=0.01). Constrictions to IRL-1620, a selective ET
B
agonist, were enhanced 11-fold in OSA compared to sham cerebral arteries (n=3-4, p<0.01). In preliminary studies, the increased sensitivity to ET-1in cerebral arteries from OSA rats was attenuated by the ET
B
antagonist, BQ-788. We conclude that OSA produces pathological changes involving decreased endothelial-derived NO production and enhances constrictor responses to ET-1 as a result of ET
B
upregulation. Since blood pressures were similar in the OSA and sham rats, we conclude that cerebrovascular dysfunction can occur with OSA in the absence of coexisting hypertension.
Abstract 158: Magnetic Resonance Angiography Signal Intensity as a Marker of Hemodynamic Impairment in Intracranial Arterial Stenosis
Authors: Leng Xinyi , Wong Ka Sing , Soo Yannie , Leung Thomas , Zou Xinying , Wang Yongjun , Feldmann Edward , Liu Liping , Liebeskind David
Published: July 2021

Background and Purpose:—
Intracranial arterial stenosis (ICAS) is the predominant cause of ischemic stroke or transient ischemic attack (TIA) in Asia. Change of signal intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may reflect hemodynamic severity of such lesions.

Methods:—
In-patients with a symptomatic single ICAS of anterior circulation on 3D time-of-flight MRA were recruited. Baseline and 1-year follow-up data were collected. Signal intensity ratio (SIR) was calculated to represent change of SIs across an ICAS on maximum intensity projections: SIR=(mean post-stenotic SI - mean background SI)/(mean pre-stenotic SI - mean background SI). Acute infarct volume was measured on diffusion-weighted images (DWI). Relationships of SIR and baseline characteristics as well as 1-year outcomes were evaluated.

Results:—
Thirty-six subjects (86.1% males, mean age 55.0 years) were recruited. Overall, mean SIR was 0.84±0.23. Mean SIR of the 23 (63.9%) anatomically severe stenoses was insignificantly lower than the 13 (36.1%) moderate stenoses (0.80±0.23 versus 0.92±0.21, p=0.126). The median baseline infarct volume for the 28 (77.8%) subjects with lesions on DWI was 2.40 cm
3
(IQR 0.80 to 5.78). SIR and acute infarct volume were significantly, linearly and negatively correlated, Spearman correlation coefficient being -0.471 (p=0.011). Two patients (5.6%) had recurrent ischemic strokes at 1-year follow-up. SIR values or acute infarct volumes were unrelated to 1-year outcomes in this initial study.

Conclusion:—
Change of signal intensity across ICAS on MRA may reflect hemodynamic and functional severity of the lesion. Future studies are warranted to further verify the relationship between this index and prognosis of stroke patients.
Abstract 17: Racial Disparities in Stroke Recognition by Prehospital Providers
Authors: Friedman Benjamin T , Delgadillo James Q , Govindarajan Prasanthi
Published: July 2021

Background:
African Americans and Hispanics are less likely to receive thrombolytics for acute ischemic stroke. Whether similar disparities exist in the prehospital setting for stroke recognition has not been studied. Our objective was to determine the differences in sensitivity and specificity of stroke recognition between racial/ethnic groups.

Methods:
This is a secondary analysis of linked prehospital and hospital based outcome data for patients presenting to hospitals within two northern California counties between 2005 and 2007. Prehospital clinical impression was obtained from the paramedic report and hospital diagnosis of stroke was identified using validated ICD- 9 codes in the discharge abstract file of the state administrative database. Patients missing data on race, ethnicity, paramedic primary impression or hospital discharge diagnosis were excluded. Sensitivity and specificity of prehospital stroke recognition among different racial/ethnic groups including Asians, Hispanics, and Non-Hispanic Whites were calculated. Independent association of race with sensitivity and specificity of prehospital stroke recognition was explored using a logistic regression model.

Results:
223,318 patients were transported by EMS during the study period; 3,633 had a primary discharge diagnosis of stroke using validated ICD-9 codes. Pre-hospital sensitivity for stroke recognition was lower among Asian (OR 0.65, 95% CI 0.54-0.79) and Hispanic patients (OR 0.74, 95% CI 0.59-0.92) when compared with Non-Hispanic Whites. Female gender was also independently associated with lower sensitivity of pre-hospital recognition (OR 0.82, 95% CI 0.71-0.940). Hispanic ethnicity and female gender were all independently associated with increased specificity.

Conclusion:
Race/ethnic and gender disparities exist in the prehospital recognition of stroke. Future efforts should explore the effects of these differences on stroke treatment rates.
Abstract 170: ApoE e4 Status and Incident Cognitive Decline among U.S. adults from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study
Authors: Wadley Virginia G , McClure Leslie A , Gillett Sarah R , Unverzagt Frederick W , Kennedy Richard E , Levine Deborah A , Kelley Brendan J , Kissela Brett M , Cushman Mary
Published: July 2021

Introduction:
ApoE genotype affects cholesterol metabolism, and carriers of the e4 allele have increased risk of heart disease, stroke, Alzheimer’s disease, vascular dementia, Mild Cognitive Impairment, and cognitive decline. Studies have yielded mixed results on the independent and interactive effects of e4 carrier status, demographics, and health variables on risk of cognitive decline.

Methods:
Drawing from a stratified random subsample of REGARDS study participants, we performed ApoE genotyping on 424 incident cognitive decline cases and 554 cohort members without cognitive decline. Participants with normal baseline cognitive status, no baseline stroke history, and sufficient longitudinal cognitive data were eligible. Incident cognitive decline was defined as a score > 1.5 SD below age-, education-, race- and sex-adjusted expected score on > 2 of 3 cognitive tests (memory, learning, executive function) at most recent assessment.

Results:
ApoE e4 carrier status interacted with age to determine odds of incident cognitive decline. In sample-weighted and fully adjusted regression models, greater risk for cognitive decline was seen in e4 carriers above but not below age 65 (Table). Stroke Belt residence, lower income, abstaining from alcohol, smoking, diabetes, heart disease, and incident stroke were independent predictors of decline after accounting for e4 carrier status and other model variables (p values < .05) (data not shown).

Discussion:
Drawing from a national cohort of black and white adults and controlling for key demographics in defining cases of substantive cognitive decline, risk for decline was higher for older ApoE e4 carriers. Risk of decline was also higher for residents of the Stroke Belt and those with low income, smoking, alcohol abstinence, CVD, or incident stroke, even after accounting for e4 and other possible confounders. Results highlight the interplay of genetics and environment in determining cognitive decline risk.
Abstract 175: Stroke and 10-year Risk of Dementia and Cognitive Impairment Among Older Mexican Americans
Authors: Mayeda Elizabeth R , Haan Mary N , Neuhaus John
Published: July 2021

Background:
Stroke is a leading cause of death in the United States and has been linked to an increased risk of dementia and cognitive impairment. The prevalence of stroke and vascular risk factors are higher among Mexican Americans than non-Hispanic whites, but the literature on stroke and dementia and cognitive impairment among this growing ethnic group remains largely unexplored.

Objective:
We evaluated the association between non-fatal stroke and incidence of dementia/cognitive impairment without dementia (CIND) in a cohort of older Mexican Americans, accounting for the competing risk of mortality.

Methods:
The present study included 1,617 participants from the Sacramento Area Latino Study on Aging (SALSA), a population-based study of Mexican Americans aged 60-98 years, who were free of dementia/CIND at baseline in 1998-1999 and followed through 2007. At annual study visits, stroke events were identified by self-report of a physician diagnosis or hospitalization and dementia and CIND cases were identified with a three-phase clinical assessment protocol. We evaluated the association between baseline and time dependent stroke and incidence of dementia/CIND with Fine and Gray competing risk regression models to account for the competing risk of mortality.

Results:
There were 221 participants with a history of stroke at baseline or who experienced a non-fatal stroke during the study. Over a mean follow-up of 6.5 years, there were 159 incident dementia/CIND cases and 298 deaths (n=61 deaths due to stroke). After accounting for the competing risk of mortality and adjusting for sex, education, waist circumference, diabetes, and systolic blood pressure, individuals with a stroke event had a three-fold increased risk of dementia/CIND compared to those with no stroke event (hazard ratio=2.97, 95% CI: 2.05-4.30).

Conclusions:
These results suggest that among older Mexican Americans, stroke is strongly associated with incidence of dementia/CIND, even after accounting for traditional vascular risk factors and the competing risk of mortality.
Abstract 176: The Feasibility of Intravenous Flat-Detector CT (IV FDCT) Angiography for Intracranial Arterial Stenosis
Authors: Sheen Seung , Jeon Jin Sue , Kim Jeong Eun , Bang Jae Seung , Son Young-Je
Published: July 2021

BACKGROUND AND PURPOSE:
Intravenous flat-detector CT (IV FDCT) angiography is an emerging technology for the detection of intracranial vascular disease. The study was conducted to determine the feasibility of IV FDCT in estimating major atherosclerotic intracranial arteries stenosis with digital subtraction angiography (DSA) as the reference.

METHODS:
DSA and IV FDCT were performed simultaneously in patients with transient ischemic attack or acute cerebral infarction. The degree and length of stenosis were measured. The stenotic vessels were categorized into four groups by the grade of stenosis: normal (<30%), mild (30-49%), moderate (50-69%) or severe (>70%). The vessels of the normal group were excluded from analysis to reduce spectrum bias. Measurement of vessels was recorded using an electric ruler by a qualified endovascular neurosurgeon and a neuroradiologist.

RESULTS:
A total of sixty-nine patients with 842 vessel segments were calculated. Mild (n=56), moderate (n=47) and severe stenosis (n=46) groups were analyzed. IV FDCT had a sensitivity of 97.6%, specificity of 96.9%, and a negative predictive value of 96.9% for detecting ≥50% stenosis and respective values of 91.9%, 98.2%, and 97.4 % for depicting ≥70% stenosis. The difference of stenotic length between two tests was not significantly difference as an increase in the severity of stenosis (Spearman’s rank test; r = - 0.12, p=0.13)

CONCLUSION:
IV FDCT can be a feasible alternative as a noninvasive method for evaluating stenosis of the major intracranial arteries.
Abstract 180: The Growth Rate of Early DWI Lesions is Highly Variable and Associated with Penumbral Salvage and Clinical Outcomes Following Endovascular Reperfusion
Authors: Wheeler Hayley M , Mlynash Michael , Inoue Manabu , Tipirneni Aaryani , Liggins John , Mishra Nishant K , Zaharchuk Greg , Straka Matus , Kemp Stephanie , Bammer Roland , Lansberg Maarten G , Albers Gregory W ,   The DEFUSE 2 Investigators
Published: July 2021

Background:
The degree of variability in the rate of early DWI expansion has not been well characterized. We hypothesized that Target Mismatch patients with slowly expanding DWI lesions have more penumbral salvage and better clinical outcomes following endovascular reperfusion than Target Mismatch patients with rapidly expanding DWI lesions.

Methods:
This substudy of DEFUSE 2 included all patients with a clearly established time of symptom onset. The initial DWI growth rate was determined from the baseline scan by assuming a volume 0 ml just prior to symptom onset. Target Mismatch patients who achieved reperfusion (>50% reduction in PWI after endovascular therapy), were categorized into tertiles according to their initial DWI growth rates. For each tertile, penumbral salvage (comparison of final volume to the volume of PWI (Tmax > 6 sec)/ DWI mismatch prior to endovascular therapy), favorable clinical response, and good functional outcome (see figure for definitions) were calculated. We also compared the growth rate in patients with the Target mismatch vs. Malignant Profile.

Results:
64 patients were eligible for this study. Target mismatch patients (n=44) had initial growth rates (range 0 to 43 ml/hr, median of 3 ml/hr) that were significantly less than the growth rates in Malignant profile (n=7) patients (12 to 92 ml/hr, median 39 ml/hr; p < 0.001). In Target mismatch patients who achieved reperfusion (n=30), slower early DWI growth rates were associated with better clinical outcomes (p<0.05) and a trend toward more penumbral salvage (n=27, p=0.137).

Conclusions:
The growth rate of early DWI lesions in acute stroke patients is highly variable; Malignant profile patients have higher growth rates than other MRI profiles. Among Target Mismatch patients, a slower rate of DWI growth is associated with a greater degree of penumbral salvage and improved clinical outcomes following endovascular reperfusion.
Abstract 193: Preliminary Clot Length Analysis of Anterior Circulation Large Vessel Occlusions:
Authors: Yoo Albert , Heck Donald , Frei Donald , Zaidat Osama , Aceves Mario , Buell Hope , Kuo Sophia , Kamalian Shervin , Morais Livia , Bose Arani , Sit Siu Po ,   for the Penumbra THERAPY Trial Investigators
Published: July 2021

Purpose:
Thin-section (≤ 2.5 mm) non-enhanced CT images may be used to reliably measure clot lengths in acute MCA occlusions, with clots ≥ 8mm long having a low probability of recanalization with IV rtPA alone. However, it is unclear what proportion of large vessel anterior circulation strokes have clot lengths ≥ 8mm and may potentially benefit from a bridging interventional approach.

Methods:
A multicenter imaging case review (target enrollment= 200 patients at 5 U.S. centers) was initiated to determine the proportion of patients meeting the below study criteria who have clot lengths ≥ 8mm. Study criteria include presentation within 8 hours of onset; imaging evidence of ICA-T, MCA M1, or M2 occlusion; and thin slice (≤ 2.5 mm) admission non-contrast CT images. Results are reported from an interim analysis of the data.

Results:
At 2 comprehensive stroke centers, all consecutive stroke admissions between August 2011 and July 2012 were reviewed for eligibility. Of these patients, 64 met study criteria (mean age= 72.3 years; 60% female; mean baseline NIHSS= 18). Mean times from symptom onset to presentation and to CT scan were 3.6 and 4.4 hours, respectively. Primary occlusions were located in the ICA-T (26.6%), M1 (64.1%), and M2 MCA (9.4%). Thrombus was visible in 92% (59/64) of cases, with lengths ranging from 3.0 to 64.8mm (mean = 18.6mm). Of these, 83% were ≥ 8mm in length. Clot length was statistically significantly longer in ICA-T occlusions and for those who did not receive IV rtPA prior to CT scan.

Conclusion:
This interim analysis suggests that the vast majority of anterior circulation large vessel occlusions have extensive (≥ 8mm length) clot burden, and may benefit from an IV-IA bridging approach. This idea will be tested in the ongoing THERAPY randomized controlled trial.
Abstract 197: Do the CHADS
2
, CHA
2
DS
2
-VASc and HAS-BLED Scores Predict Recurrent Stroke and GI Bleeding in Patients with Acute Ischemic Stroke or TIA and Atrial Fibrillation?
Authors: Silver Frank L , Stamplecoski Melissa , Fang Jiming , Kapral Moira K
Published: July 2021

Background:
In patients with atrial fibrillation (AF) the CHADS
2
and CHA
2
DS
2
-VASc score are used to provide a risk for subsequent stroke and the HAS-BLED score for hemorrhage. These scores were derived from large cohorts of patients with AF, however, only 8 - 25% of the patients had a past history of stroke. We wanted to determine whether these prediction scores had utility in patients with AF who have had a recent stroke or TIA.

Methods:
We selected patients with AF and a first stroke or TIA from the 2002-3, 2004-5, 2008-9 and 2010-11 Ontario Stroke Audits (OSA). The OSA includes data from a simple random sample of 15 - 20% of stroke and TIA patients presenting to all Ontario hospitals identified using ICD-10 diagnostic codes I60, I61, I63, I64, H34.1 and G45. Recurrent ischemic stroke, hemorrhagic stroke and major GI hemorrhage were obtained by linking the OSA data to administrative databases for hospital admissions in the subsequent year.

Results:
There were 3,960 patients with AF in the OSA who were discharged alive following their first acute stroke or TIA. The median age was 80. At discharge 41% of the patients were prescribed anticoagulants, 24% antiplatelet therapy, 25% both and 9% were prescribed no antithrombotic therapy. The one year readmission rate for stroke was 5.3% (including 0.4% hemorrhagic stroke) and 1.9% for major hemorrhage. Multivariable logistic regression models did not show any significant association between the CHADS
2
and CHA
2
DS
2
-VASc scores and the risk of recurrent stroke. The HAS-BLED score failed to predict hemorrhagic stroke or major bleeding and the risk of major bleeding for the entire group at one year was low (1.9%). Patients prescribed anticoagulants at discharge had fewer recurrent strokes (OR 0.55; 95% CI 0.34 - 0.90, p=0.02), a lower one year mortality (OR 0.42; 95% CI 0.31 - 0.56, p <0.001) and the same risk of major bleeding as compared to patients not receiving anticoagulants.

Conclusions:
The CHADS
2
, CHA
2
DS
2
-VASc and HAS-BLED scores did not predict recurrent stroke or hemorrhage in patients following an acute stroke or TIA. Anticoagulation at discharge was associated with a lower risk of recurrent stroke and death without a significant increase in the risk of major hemorrhage.
Abstract 216: Minimally Invasive Surgery plus Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) Leads to a Reduction in Perihematomal Edema
Authors: Mould W. Andrew , Carhuapoma J. Ricardo , Muschelli John , Hanley Daniel F ,   and the MISTIE Investigators
Published: July 2021

Background:

Intracerebral hemorrhage (ICH) remains the most devastating form of stroke without treatment. Secondary damage such as perihematomal edema (PHE) can negatively impact long-term outcome. Several reports suggest that blood and its degradation products lead to PHE. Treatments aimed at blood removal and edema prevention have a potential to improve outcome in these stroke patients. We hypothesized that successful hematoma evacuation would reduce PHE volume.

Methods:

MISTIE is a multi-center, prospective, randomized trial testing the safety and efficacy of hematoma evacuation after spontaneous ICH compared to medical management. Study interventions were consistently applied in a protocol-based manner across study sites. We conducted a semi-automated, computerized volumetric analysis on CT imaging to assess the effect of hematoma removal on PHE. Both arms of the study were assessed for ICH and PHE volumes at two time points: T1, pre-enrollment, and T2, end of treatment.

Results:

Of 123 patients enrolled, 79 surgical and 39 medical patients were analyzed. There was no significant difference between the treatment cohorts in age, enrollment GCS, intraventricular involvement, baseline ICH volume, or baseline PHE volume. Mean hematoma volume at T2 was 19.64±14.5 cc for the surgical cohort and 40.74±13.9 cc for the medical cohort (p<0.001). Mean edema volume at T2 was 27.67±13.3 cc for the surgical cohort while medical patients had 41.69±14.6 cc (p<0.001). When patients within each treatment arm were subdivided into groups of >65%, 20-65%, and <20% ICH removal, surgical patients were 32, 39, and 8 respectively, whereas all medical patients experienced <20% clot removal. A significant difference in edema volume was seen among the three groups (ANOVA p<0.001). On further analysis, there was a positive correlation between edema reduction and percent of ICH removed: the more ICH removed, the greater the reduction in edema (Spearman R=0.645; p<0.001).

Conclusion:

Safe, early, and effective hematoma evacuation of parenchymal blood in ICH is associated with significant reduction in perihematomal edema, especially when a high percentage of blood is removed.
Abstract 31: The Development and Validation of a Biochemical Biomarker Panel to Detect Acute Stroke: A Preliminary Study
Authors: Sharma Richa , Macy Stephanie , Richardson Kara , Lokhnygina Yuliya , Laskowitz Daniel
Published: July 2021

A Biochemical Biomarker Panel Detects Acute Ischemic Stroke and Intracerebral Hemorrhage

INTRODUCTION:
The accurate diagnosis of acute ischemic stroke(IS), intracranial hemorrhage(ICH), and stroke mimics is essential for administering appropriate time-sensitive therapies which are currently underutilized due to diagnostic uncertainty.

HYPOTHESIS:
We hypothesize that a panel of biomarkers which singly predict inflammation, neuronal injury, and glial activation together may be diagnostic of acute cerebral ischemia with clinically relevant discriminative capacity.

METHODS:
Serum samples were collected from 167 patients presenting with acute neurologic deficits within 24 hours of symptom onset. Patients were classified as IS if symptoms fit a vascular distribution, if they had either a radiographically apparent lesion, and/or symptoms persisting more than 24 hours. Presentation CT determined ICH. Mimics were those with confirmed non-vascular etiologies of neurologic deficits. Of the 262 biomarkers measured, those significant in univariate analyses underwent stepwise selection from which a 5-biomarker multivariate logistic model was built and internally validated by bootstrapping. Its capacity to discriminate IS versus mimic, IS versus ICH, and IS plus ICH versus mimic was evaluated by area under the receiver operating characteristic, equivalent to concordance index (c-index) in logistic regression analysis.

RESULTS:
The 5-biomarker model consisted of eotaxin, epidermal growth factor receptor(EGFR), S100A12, metalloproteinase inhibitor-4(MPI-4), and prolactin. When discriminating between IS and mimics, eotaxin (c=0.812), EGFR(c=0.690), S100A12 (c=0.605), MPI-4 (c=0.588), and prolactin (c=0.645) together yielded a c-index of 0.918. With age, race, and gender, the sensitivity, specificity, and negative predictive value of the model were 90.3%, 85.2%, and 92.0%, respectively. This model also predicted IS plus ICH versus mimic (c= 0.927), and IS versus ICH (c = 0.896).

CONCLUSIONS:
The biomarkers identified in this study are essentially novel and show promise in acutely distinguishing IS, ICH, and mimics. Such a biomarker panel may assist in the early evaluation and management of patients with stroke-like symptoms.
Abstract 39: Adrenal ßArrestin1 Raises Serum Aldosterone Levels And Blood Pressure, Both Significant Stroke Risk Factors, In Experimental Rats And Mice
Authors: Lymperopoulos Anastasios , Bathgate Ashley , Salazar Norma C
Published: July 2021

Introduction:
It is widely accepted nowadays that elevation of serum levels of aldosterone, a mineralocorticoid hormone with toxic effects in several cardiovascular tissues, including the heart and cerebral blood vessels, can significantly raise stroke risk. The success of mineralocorticoid receptor blockers, such as eplerenone, at preventing stroke attacks attests to this. Aldosterone is normally produced and secreted by the adrenal cortex in response to angiotensin II. We recently reported that adrenal βarrestin1 (βarr1) plays a crucial role in the physiological angiotensin II-stimulated aldosterone production in the adrenal cortex, leading to marked elevation of circulating serum aldosterone levels in vivo (Lymperopoulos A. et al., Proc. Natl. Acad. Sci. USA. 2009;106:5825-5830).

Hypothesis:
Herein, we examined the potential impact of this adrenal βarr1-dependent aldosterone elevation on stroke risk in experimental animals in vivo.

Methods:
We used the βarr1 knockout (βarr1KO) mouse model, studying it alongside wild type (WT) control mice, and also adult male Sprague-Dawley rats, in which adrenal βarr1 was overexpressed in vivo via adrenal-targeted adenoviral-mediated βarr1 gene transfer. Serum aldosterone was measured by ELISA and blood pressure via telemetry.

Results:
Serum aldosterone at 7 days post-in vivo gene delivery was markedly elevated in adrenal βarr1-overexpressing rats (536+50 pg/ml), compared to control rats receiving the green fluorescent protein (GFP) adenoviral transgene (235+40 pg/ml, p<0.05, n=5). This translated to a significant increase in mean arterial pressure of the βarr1-overexpressing rats (155+5 mmHg) compared to control GFP-expressing rats (137+8 mmHg, p<0.05, n=5), again at 7 days post-in vivo gene delivery, which was prevented by concurrent eplerenone treatment. In contrast, βarr1KO mice had significantly lower serum aldosterone levels (270+20 pg/ml) compared to WT controls (498+35 pg/ml, p<0.05, n=5), at 4 weeks post-experimental myocardial infarction.

Conclusions:
Adrenal βarr1 up-regulation can dramatically increase circulating aldosterone levels and systemic blood pressure, thus conferring increased risk for stroke in experimental rodents.
Abstract 43: Predicting Clinical Outcomes After Thrombolysis in Patients with Diabetes in Acute Ischemic Stroke
Authors: Nikneshan Davar , Jitphapa Pongmoragot , Raptis Stavroula , Zhou Limei , Saposnik Gustavo ,   Registry of the Canadian Stroke Network (RCSN),   The Stroke Outcomes Rsch Canada (SORCan) Working Group
Published: July 2021

Background:
Diabetes is a well-known stroke risk factor that is associated with poorer stroke outcomes. Limited tools are available to evaluate clinical outcomes and response to thrombolysis in stroke patients with Diabetes.

Methods:
We applied the iScore (www.sorcan.ca/iscore), a validated risk score, to stroke patients presenting to stroke centers participating in the Registry of the Canadian Stroke network (RCSN).

Outcome measures:
Favorable outcome (defined as a modified Rankin scale 0-2) at discharge after thrombolysis. Secondary outcomes included intracerebral hemorrhage, death at 30-days and at 1-year stratified by tertiles of the iScore.

Results:
Among 12,686 patients with an acute ischemic stroke, 3,228 (25.5%) had diabetes. Patients with diabetes had higher likelihood of death or disability (mRS>3) at discharge after thrombolysis compared to patients without diabetes (75.7% vs. 68.9%; RR 1.01 95%CI 1.02-1.18). The risk of intracranial hemorrhage (any type or symptomatic) was not different in patients with or without diabetes (12.6% vs. 12.5%; RR 1.01, 95%CI 0.72-1.4 and 7.5% vs 6.8%; RR 1.11, 95% CI 0.7-1.72 respectively). In the logistic regression analysis, there was an interaction between tPA and the iScore (p<0.001), but there was no interaction between diabetes and the iScore or tPA.

Conclusion:
Stroke patients with diabetes had higher mortality. The iScore similarly predicted a clinical response after tPA in both patients with and without diabetes. ICH was similar in both groups.