bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 78: Cerebral Hemodynamic and Cognitive Performance in Bilateral Asymptomatic Carotid Stenosis
Authors: Balucani Clotilde , Viticchi Giovanna , Falsetti Lorenzo , Silvestrini Mauro
Published: July 2021

Background:
Preliminary studies have reported cognitive dysfunction in unilateral asymptomatic carotid stenosis (ACS). Impaired cerebral hemodynamic status measured by cerebrovascular reactivity has been associated with cognitive dysfunction in unilateral ACS.

Objectives:
(1) To evaluate cognitive performance in bilateral ACS compared to unilateral ACS and healthy subjects and (2) to explore the relationship between cognitive performance and cerebral hemodynamic status in bilateral ACS.

Method:
Asymptomatic patients with ultrasound evidence of bilateral or unilateral ACS (60%-99% diameter reduction) were prospectively collected. Healthy subjects (HS) comparable for demographics and vascular risk profile served as controls. A neuropsychological investigation included phonemic and categorical Verbal Fluency (VF) tests to explore the left hemisphere and Colored Progressive Matrices (CPM), and Complex Figure Test Copy (CFTC) tests to explore the right hemisphere. Cerebrovascular reactivity (CVR) to hypercapnia using the transcranial Doppler (TCD) based breath-holding index (BHI) test was performed in each subject. Impaired CVR was defined as a BHI < 0.69. Generalized linear multivariate and univariate models were employed to evaluate the mean difference on left and right cognitive test abilities in bilateral ACS patients with left and right preserved or impaired CVR. Vascular risk factors, education years, mini-mental status examination (MMSE), and current medications were included as covariates.

Results:
Three-hundred-thirty-three consecutive subjects were included: 126 bilateral ACS; 73/75 left/ right unilateral ACS; 56 HS; mean age: 70 ± 3.78 yrs; males: 65%; education years: 10.3±3.7; MMSE score: 26.7±1.27. Bilateral and unilateral ACS patients showed significantly lower scores in all cognitive tests compared to HS (p<0.05). In the multivariate analysis, among bilateral ACS an impaired CVR in the right side was associated with a significantly reduced CPM score: from an estimated mean of 32.6 [95% Confidence Interval (CI): 29.8-35.4) to 23.0 (95% CI: 20.2-25.8) and the CFTC score from 34.7 (95% CI: 32.0-37.4) to 26.0 (95% CI: 23.3-28.7). Similarly, an impaired CVR on the left side was associated with a reduced phonemic VF score: 13.5 (95% CI: 11.2-15.8) to 7.5 (95% CI: 5.4-9.7) and categorical VF score from 21.1 (95% CI: 18.1-24.1) to 12.3 (95% CI: 9.5-15.1). All comparisons were p<0.05.

Conclusion:
Patients with unilateral or bilateral ACS are more likely to suffer cognitive dysfunction compared to healthy controls. Impaired CVR predicts the development of cognitive dysfunction in bilateral ACS. A non-invasive assessment of CVR using the TCD-based BHI test may contribute to a more comprehensive risk stratification in these patients.
Abstract 90: Socioeconomic Status Is Associated With Disability Following Acute Ischemic Stroke: Findings From The Adherence eValuation After Ischemic stroke-Longitudinal (AVAIL) Registry
Authors: Prvu Bettger Janet , Zhao Xin , Bushnell Cheryl , Zimmer Louise , Xian Ying , Pan Wenqin , Olson DaiWai , Peterson Eric D
Published: July 2021

Background:
Socioeconomic status (SES) is widely recognized as an area of inequity that affects health outcomes. However, social determinants of health are less frequently measured in longitudinal studies of acute stroke patients. The relationship of SES on disability 3-months post-stroke is unknown.

Methods:
We analyzed ischemic stroke patients in the AVAIL registry who were enrolled at 98 hospitals participating in Get With The Guidelines-Stroke. Patients who died (n=64) or did not complete a modified Rankin Scale (mRS) at 3-months (n=154) were excluded. Multivariable logistic regression was used to examine the relationship of SES (defined by level of education, work status, and perceived adequacy of household income to meet needs) and disability (mRS scores 3-5).

Results:
Among the 2092 stroke patients who met eligibility criteria, the mean age was 65.5 ± 13.7, 44.2% were female, and 82.7% were White. Fifty seven percent had a high school or less education, 11.4% were not working post-stroke and were home not by choice, and 25.7% were without an adequate household income. A third of the sample had some level of disability at 3-months (34.6% mRS 3-5). Those with disability were more likely to be older, non-White, female, single, less educated, have inadequate income, and were home not by choice. In the multivariable analysis, lower education, inadequate income, and being home but not by choice (compared with those who returned to work) were independently associated with disability (p<0.01;
Table
).

Conclusion:
In this national cohort of stroke survivors, socioeconomic status as measured by level of education, work status, and income were independently associated with post-stroke disability.
Abstract 99: Impact of Acute Perihematomal Edema on Long Term Outcomes Following Primary Intracerebral Hemorrhage
Authors: Strand Adam T , Sobotka Ian , Wing Jeffrey J , Menon Ravi S , German Laura , Burgess Richard E , Gibbons M. C , Shara Nawar M , Fernandez Stephen , Jayam-Trouth Annapurni , Edwards Dorothy F , Kidwell CS
Published: July 2021

Introduction:
The impact of acute perihematomal edema (PHE) as an independent predictor of clinical outcomes following an intracerebral hemorrhage (ICH) has been controversial. To date, some studies have reported that PHE is associated with poorer outcomes, while others have found an association with good outcomes. The goals of the current analysis were to 1) identify predictors of acute PHE, and 2) determine impact of PHE on clinical outcomes in a predominantly African American hypertensive ICH population.

Methods:
Subjects with spontaneous non-traumatic ICH who were prospectively enrolled in the DiffErenCes in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) Project were included in the analysis. Baseline MRIs were performed in subjects at median of 2 days from onset. Hematoma volume as well as PHE were calculated from GRE and FLAIR sequences, respectively, employing a semiautomated volumetric analysis. PHE volume was expressed as a percent of the hematoma volume (PHEv/ICHv x 100). Outcome measures included year 1 NIHSS score using a log-linear model and dichotomized (0-2 vs. 3-6) modified Rankin Scale (mRS) using a logistic regression model.

Results:
A total of 140 subjects were included in the analysis. Mean age was 59, 58% were male, 75% were black, and 85% had a history of hypertension. Baseline NIHSS score was mean 9 (median 6), mean ICH volume was 25 cc (range 0.5-136 cc), and mean relative PHE percent was 115% (range 0-559%). Independent predictors of PHE on multivariate analysis included ICH volume (p=0.004) and antiplatelet use on admission (p=0.02). At the year 1 timepoint, there was no significant association between the severity of PHE percent and good or poor outcome based on dichotomized mRS (p=0.67); however there was a modest trend towards an association between increased edema and lower NIHSS scores (p=0.15).

Conclusions:
In this large MRI-based cohort of patients with primary ICH, acute perihematomal edema measured on FLAIR sequences was not an independent predictor of poor functional outcome at year 1 employing the mRS. However, there was a modest trend towards an association between increased relative edema volume and lower year 1 NIHSS scores, which may suggest a protective effect of edema on outcome. Further studies in a larger cohort are needed to clarify the impact of both acute and peak perihematomal edema on outcome following primary ICH.
Abstract 112: Unsustainable Hospital Costs in the treatment of Medicare Beneficiaries admitted with Aneurysmal Subarachnoid Hemorrhage
Authors: Kainth Daraspreet S , Adil Malik M , Kainth Hunar S , Qureshi Adnan
Published: July 2021

Background:
Rising medical expenditures and the discrepancies in Medicare reimbursements have placed restraints on the health care delivery system. The goal of this study is to quantify these differences in the management of Medicare beneficiaries admitted with aneurysmal subarachnoid hemorrhage and to evaluate the sustainability of our current health care reimbursement practices.

Material and Methods:
Patients entered in the Nationwide Inpatient Sample between 2009 and 2010, with International Classification of Diseases codes for a diagnosis of ruptured aneurysm who underwent either surgical or endovascular treatment of the cerebral aneurysm, were included in the study. Factors associated with higher hospitalization cost were identified and correlations with age, sex, medical co morbidities, and discharge status were examined.

Results:
In 2009 and 2010, the average hospital charges for the 9,097 Medicare patients admitted with a ruptured aneurysm were $270,937 for patients treated with endovascular and $259,131 for patients treated with surgical treatment. These charges are substantially higher than the 2008 average Medicare (MS-DRG) payment, $36,304 for treatment of patients with co morbidity, and $30,380 without co morbidity. A greater number of endovascular treatments were performed, 6290, compared to 2807 surgical treatments. Of both treatments, women were more frequently treated. 78.4% of surgical treatments and 73.3% of endovascular treatments were for women. A higher percentage of patients treated with endovascular treatment had minimal disability at discharge compared with patients treated with surgical treatment (26.9% vs 16.8%, p = 0.005). However, the re-imbursement of both treatments was equivalent.

Conclusions:
Hospitalization charges for the care of Medicare beneficiaries who undergo surgical or endovascular treatment of ruptured aneurysms are significantly higher than Medicare reimbursement. Women undergo the majority of treatments and endovascular treatment appears to be associated with less disability at discharge. The current discrepancies in hospital expenses and reimbursement may lead to unsustainable healthcare delivery for these patients.
Abstract 126: Inpatient Rehabilitation Facility Disposition Improves Odds For Good Clinical Outcome After Endovascular Stroke Reperfusion Therapy
Authors: Belagaje Samir R , Patel Vishal , Sun Chung-Huan , Pimentel Cedric , Glenn Brenda , Horn Christopher , Thomas Tommy , Nogueira Raul , Anderson Aaron , Frankel Michael , Gupta Rishi
Published: July 2021

INTRO:
A person with stroke has improved outcomes with post-acute care in an inpatient rehabilitation facility (IRF) compared to those who are discharged to a skilled nursing facility (SNF). However, this research was conducted in an era before acute stroke treatment was widely implemented. Endovascular reperfusion reduces ischemic stroke volume; however treatment effect may be diluted by discharge disposition. In this analysis, we hypothesize that patients will have better 90 day outcomes if they are discharged to a IRF or home compared to a SNF.

METHODS:
Subjects were identified from a prospective database tracking clinical outcomes of patients treated with endovascular reperfusion from a single primary care stroke center. Data included discharge disposition, NIHSS, THRIVE, HIAT-2, & APACHE II scores, and successful reperfusion. Univariate analysis was performed to assess predictors of good clinical outcome as defined by 90 day modified Rankin scores (mRS) ≤ 2. A binary logistic regression model was used to determine the impact placement to IRF versus a SNF on clinical outcomes.

RESULTS:
177 subjects were included in the analyis; mean age was 66±14 and median NIHSS was 20. Modified APACHE II, NIHSS, THRIVE, & HIAT-2 scores were not different between the two groups Discharge dispositions included: 35(19.8%)home, 38(21.5%) IRF, 47(26.6%)SNF and 57(32.3%) died/went to hospice. Of the 85 patients discharged to SNF or IRF, only 26% of patients discharged to SNF compared to 50% to IRF achieved a good clinical outcome (p-value <0.03). In binary logistic regression modeling, after adjusting for age, infarct volume, pre-treatment ASPECT & NIHSS scores, and modified APACHE II score, disposition to SNF was significantly associated with a lower probability of achieving a mRS of 0-2 at 90 days, OR 3.31(95%CI 1.06-9.62, p<0.04).

CONCLUSIONS:
In our study, subjects discharged to SNF and IRF after thrombectomy have similar medical and neurological severity at admission and similar final infarct volumes at discharge. Despite these similarities, patients discharged to SNF had a significantly lower probability of achieving a good neurological outcome. Further study is required to determine if IRF could be considered in more patients to improve clinical outcomes.
Abstract 136: Deleterious Effects of Synaptic Zn2+ in a Murine Distal Middle Cerebral Artery Occlusion Model
Authors: Carlson Andrew P , Li Lu , Thomas Kelsey , Sheline Christian , Shuttleworth William
Published: July 2021

Background:
Previous work has implicated accumulation of Zn2+ as a contributor to ischemic brain injury, however the sources of toxic Zn2+ accumulation are not fully understood. Previous data report that ICV delivery of a Zn2+ chelator limited mild focal stroke (Neuroscience 115 (2002) 871-8). We have recently demonstrated substantial synaptic Zn2+ release following spreading depolarization (JCBFM 31 (2011) 1073-84), and thus it is possible that repetitive spreading depolarization_ known to occur following stroke_ could be a major source of toxic Zn2+. In the present study, we examined whether synaptic Zn2+ release contributes to neuronal injury in a murine focal stroke model.

Methods
The effect of synaptic Zn2+ was assessed using mice lacking synaptic Zn2+, due to genetic deletion of the synaptic vesicle transporter ZnT3 (ZnT3 KO). Wild type C57Bl/6 mice were age and sex matched as controls. Mice were anesthetized with isofluorane and the cortical branch of the right middle cerebral artery was cauterized via a temporal burrhole. A single surgeon performed the occlusions. Body temperature was maintained at 37±0.5oC during the procedure and recovery. Animals were allowed to recover for 1 week before euthanasia. Stroke volume was assessed by Fluoro-Jade staining. Statistical analysis with 2-way ANOVA was used to determine the effects of sex and genotype on stroke volume.

Results:
There was no peri- or post-procedural mortality. Infarct was confirmed histologically in all animals. Stroke volume was reduced in the ZnT3 KO mice compared to wild type (mean volume 3.54mm3 versus 8.42mm3 respectively, n=7 for each arm). Only genotype (not sex) had a significant effect on stroke volume by 2-way ANOVA (p=0.0042).

Conclusion:
Synaptic Zn2+ release leads to increased stroke volume, likely due to toxic Zn2+accumulation. Therapies targeting synaptic release of Zn2+ or repetitive spreading depolarization events (which cause Zn2+ release) may decrease delayed ischemic injuries.
Abstract 140: Electronegative LDL and Beta-Amyloid Synergistically Induce Platelet Activation that Can Be Inhibited by Novel MicroRNA-145 and NF-κB Decoys
Authors: Shen Ming-Yi , Sheu Joen-Rong , Chen Fang-Yu , Dixon Richard AF , Chen Chu-Huang
Published: July 2021

Background:
In addition to its role in Alzheimer’s disease, β-amyloid (Aβ) stimulates platelet aggregation by activating NF-κB. L5, a highly electronegative atherogenic subfraction of low-density lipoprotein (LDL), also induces platelet activation. Our preliminary experiments showed that Aβ and L5 function synergistically; thus, we examined the underlying mechanisms and tested a novel therapeutic approach using oligodeoxynucleotide (ODN) decoys.

Methods and Results:
Human plasma LDL was separated into 5 subfractions, L1-L5, with increasing electronegativity. L5, but not L1-L4, induced human platelets to release Aβ from α-granules. By phosphorylating IκB kinase β (IKKβ), both L5 and Aβ induced degradation of kappa B inhibitor (IκBα) to activate NF-κB. This led to, by way of c-Jun N-terminal kinase (JNK), the activation of platelet receptor GPIIbIIIa and platelet aggregation. L5- and Aβ-induced IκBα degradation was inhibited by ubiquitin-specific peptidase 31 through deubiquitination, which was in turn inhibited by microRNA (miR)-145. However, a specific miR-145 decoy ODN prevented IκBα degradation by inhibiting miR-145 (Figure), whereas scramble ODN had no effect. Furthermore, a specific NF-κB decoy prevented NF-κB-mediated GPIIbIIIa activation (Figure). Compared to L1, L5 injected into C57/BL6 mice (5 mg/kg of each twice a week for 6 weeks) shortened tail-bleeding time by 38% (n=6;
P
<0.05), which was prevented by NF-κB decoy but not scramble ODN.

Conclusions:
Atherogenic L5 LDL potentiates Aβ-mediated platelet activation and aggregation. Novel miR-145 and NF-κB decoys effectively blocked the synergistic effect of L5 and Aβ and may reduce the risk for thrombotic stroke.
Abstract 142: Latino Stroke Survivors More Likely to Experience Depression
Authors: Fei Kezhen , Benn Emma K , Negron Rennie , Tuhrim Stanley , Horowitz Carol R
Published: July 2021

Background:
Literature suggests that White Americans experience more depression in general, and post-stroke depression than non-White Americans, but depression disparities have not been well-explored. We aimed to characterize this association by applying a novel ‘Rank and Match’ secondary analytic method, based on the Institute of Medicine’s disparity framework to a multi-racial/ethnic stroke cohort.

Methods:
We recruited a cohort of community-dwelling adults who had a stroke in the past 5 years, from Harlem and the South Bronx in New York City, to a recurrent stroke prevention intervention. At baseline, we measured depression using the PHQ-8 scale and patients’ health status, demographics, comorbidities and socioeconomic status (SES), including income and education. We used multivariate logistic regression to evaluate the impact of race/ethnicity, after adjusting for health status and SES, on having depression (using a score ≥ 10 as depressed). Then based on the IOM’s disparity framework, we used our "Rank and Match" method to assess racial/ethnic differences in depression after matching Latinos and non-Latinos by their health status rank.

Results:
The cohort included 600 participants, with a mean of 1.9 years after stroke, mean age of 63 years, 42% were Black, 39% Latino, 60% female, 56% lived below poverty, 29% had Medicaid and 31% had less than a high school degree. Participants with depression (n=178; 30%) were more likely young (p=0.002), Latino (p<0.0001), receiving Medicaid (p<0.001), and had more comorbidities (p=0.004) than non-depressed participants. The adjusted odds of depression for Latinos was 3.45 (95% CI: 1.48 - 8.07) times higher than for Whites and 2.22 (95% CI: 1.45 - 3.38) times higher than for Blacks. After applying the “Rank and Match” method, the difference between Latinos and Whites became stronger (OR=4.65; 95% CI: 1.91 - 11.30), and the difference between Latinos and Blacks sustained (OR=2.19; 95% CI: 1.41 - 3.40).

Conclusion:
This study newly reveals a high depression burden among Latino stroke survivors, particularly in comparison with non-Latinos. Future research is needed to further study this disparity, and to address depression in this population.
Abstract 171: CRP, IL-18, and BNP are Associated with Regional Brain Atrophy: Results from the Dallas Heart Study
Authors: Lucarelli Richard T , Khera Amit , Peshock Ronald M , McColl Roderick , Ayers Colby , Weiner Myron F , King Kevin S
Published: July 2021

Purpose:
Multiple biomarkers have been associated with total brain atrophy. However, little is known about their relationship to segmental atrophy in a large, multi-ethnic, population-based sample.

Materials and Methods:
3D-MPRAGE brain images obtained at 3T from 2082 participants of the Dallas Heart Study (DHS) 2 were analyzed with Freesurfer and outlier analysis was performed. Divisive eigenvalue clustering of 89 brain segments yielded 24 groups with linked atrophy patterns. Plasma C-reactive protein (CRP), IL-18, homocsysteine and B-type natriuretic peptide (BNP) obtained 7 years prior during DHS 1 were available for 1343, 840, 1333 and 1331 participants, respectively. Multivariate linear regression analysis with adjustments for age, ethnicity, and gender were used to demonstrate associations between biomarkers and atrophy clusters.

Results:
Nine atrophy clusters were associated with CRP, three atrophy clusters were associated with IL-18, and six atrophy clusters were associated with BNP (Table 1). Homocysteine did not have any significant correlations.

Conclusions:
The markers studied had associations with distinct patterns of segmental atrophy indicating they may have unique interactions in different brain regions. This suggests that distinct inflammatory and other pathways may be at work in specific regions of the brain and that their localized effects may be obscured by approaches evaluating solely total brain volumes. Table 1:
Abstract 177: Absent Collateral Flow on CT Angiogram Predicts Acute Hemorrhagic Transformation in Ischemic Stroke
Authors: Burgess Richard , Cheng Ching Esteban , Wisco Delora , Man Shumei , Uchino Ken , Toth Gabor , Hussain M. Shazam
Published: July 2021

Background:
In patients with a large vessel occlusion, the degree of collateral vascular supply to an ischemic territory has been shown to be a predictor of stroke outcome. Prior studies have focused on the correlation between collateral flow measured on conventional digital subtraction angiography and outcome measures, including the presence of hemorrhagic conversion. CT/CTA is more widely available and more quickly accomplished than MR or conventional angiography. In this work we demonstrate that the absence of CT angiographic collaterals predicts hemorrhage transformation in acute ischemic stroke patients that have persistent vessel occlusion.

Methods:
Retrospective review of patient data from a prospectively acquired database identified acute ischemic stroke patients who underwent CT angiography followed by cerebral angiography, and post procedure non-contrast CT scans. Blinded evaluators independently assessed CT angiogram collaterals, angiographic TICI scores, and the presence and severity of post procedure hemorrhagic transformation. Fishers exact test was used to compare proportions between groups.

Results:
146 patients were included. The mean age was 67. The median NIHSS was 15.5 (range 0-32). 34% of patients had any type of hemorrhagic conversion. Of patients with no collaterals on CT angiography, 63% had hemorrhagic conversion versus 23%, 33%, and 38% for patients with grades 1, 2, and 3 collaterals (p<0.05 for comparisons). Patients with TICI scores of 0 or 1 and no CTA collaterals all had hemorrhagic transformation.

Conclusion:
The absence of collateral flow on CT angiography in patients without recanalization strongly predicts the acute development of hemorrhagic conversion.
Abstract 183: Antithrombotic Therapy and Bleeding Risk in a Prospective Cohort Study of Patients with Cerebral Cavernous Malformations (CCM)
Authors: Stapf C , Hervé D , Guichard J P , Bresson D , Soumaré A , Tzourio C , Riant F , Tournier-Lasserve E , Chabriat H , Schneble H M
Published: July 2021

BACKGROUND:
Cerebral cavernous malformation (CCM) are the most frequently diagnosed vascular malformations in the brain and are often asymptomatic. The potential risk of hemorrhage often precludes antithrombotic treatment in patients with cardiovascular disease, but no systematic study has been undertaken to evaluate the effect of blood-thinning therapy on the risk of CCM hemorrhage.

PATIENTS AND METHODS:
We prospectively followed consecutive patients with a diagnosis of one or more CCMs in a prospective database since 2008. Retrospective data collection was used for patients with a diagnostic event or imaging studies done prior to first assessment. Symptomatic hemorrhage and other focal neurological events during prospective follow-up were defined according to the current guidelines of the Angioma Alliance Scientific Advisory board

RESULTS:
A total of 87 patients were prospectively enrolled in our cohort (50 women (57%), mean age 44.8 years (SD +/- 17.6), mean follow up 3.9 years) harboring a total of 738 CCMs. N=55 patients (63%) had a single CCM, and 32 patients (37%) had multiple CCMs. Longitudinal follow-up included 16 (18%) patients receiving long-term antithrombotic therapy by antiplatelet treatment (n=11) or oral anticoagulants (n=5). During 5536 lesion-years of observation, none of the patients under antithrombotic therapy experienced CCM hemorrhage on follow up.

CONCLUSION:
Our observational data suggest long-term antithrombotic treatment by antiplatelet drugs or warfarin does not increase the frequency of CCM-related hemorrhage. Patients harboring single or multiple CCMs suffering ischemic stroke or heart disease should not be withheld antithrombotic therapy.
Abstract 191: Neurorestorative Therapy For Stroke In Type 2 Diabetic Rats Using Bone Marrow Stromal Cells
Authors: Yan Tao , Chopp Michael , Zacharek Alex , Ning Ruizhuo , Roberts Cynthia , Chen Jieli
Published: July 2021

Objective:
Treatment of stroke may differ between the diabetic (DM) and non-DM stroke populations. Cell therapy with bone-marrow-stromal cells (BMSC) initiated at 24h after stroke improves functional recovery in non-DM rats, but not in type one DM rats. However, the effect of BMSC treatment of stroke in type two DM (T2DM) is unknown and is the subject of this investigation.

Methods:
T2DM was induced with high fat diet and low dose of streptozotocin. T2DM rats were subjected to 2h of middle cerebral artery occlusion (MCAo), then treated with either BMSC (5X106) or vehicle (n=8/group) initiated at 3 days after MCAo and monitored for 28 days. A battery functional tests, and vascular and white matter changes and protein expression were measured in the ischemic brain.

Results:
BMSC treatment significantly improved functional outcome at 14 and 21 days after MCAo in T2DM rats. However, the functional benefit was lost at 28 days after MCAo. BMSC significantly increased vascular and white matter remodeling identified by an increase of vascular density (vWF: 403±35/mm2 vs 303±17/mm2), cerebral arteriole number (aSMA 65.0±6.9/mm2 vs 38.6±4.4/mm2), Bielschowsky silver (axon marker, 26±2.4% vs 18±1.8%) and Lucifer fast blue (myelin marker, 39±3.1% vs 25±3.5%) expression in the ischemic boundary zone (IBZ). To test the mechanisms underlying the BMSC induced neurorestorative effects, decreased RAGE and Angiogenin expression were observed in the IBZ (RAGE: 3.1±0.4% vs 13.2±3%; Angiogenin: 9.5±2.2% vs 27.7±5.2%) of BMSC treated rats. However, BMSC treatment significantly increased internal carotid wall thickness (23.4±1.5μm vs 17.9±0.6μm), artery intimae thickness (11.1±0.6μm vs 7.6±0.5μm), and cerebral artery wall thickness (10.5±0.8μm vs 6.4±0.2μm); and significantly decreased cerebral artery diameter (26.5±1.7μm vs 36.3±2.8μm) compared to vehicle control.

Conclusion:
BMSC therapy in T2DM-MCAo significantly improved early functional outcome, but did not improve long term functional outcome. BMSC promote vascular and white matter remodeling, but increase cerebral artery neointimal hyperplasia. The increased cerebral artery neointimal hyperplasia may contribute to the failed improvement long term functional outcome after stroke in T2DM rats.
Abstract 194: Preliminary Results from the FIRST Trial: Natural History of Acute Stroke from Large Vessel Occlusion
Authors: Janardhan Vallabh , Gianatasio Ryan M , Chen Sherman H , Bhuva Parita , Murray Mark M , Santos Patricia , Guthmann Anita , Vijayappa Madhu B , Hansen Paul A , Misra Vivek , Cheung Raymond , Leung Thomas , Grunwald Iris , Hernandez Heather , Barraza Leticia , Buell Hope , Kuo Sophia , Bose Arani , Sit Siu Po ,   for the Penumbra FIRST Trial Investigators
Published: July 2021

Purpose:
Current literature has limited information on the natural history of the stroke cohort eligible for mechanical thrombectomy. The placebo group from the PROACT II study is often used as a historical control, despite differences in entry criteria. Reported herein are data in a stroke cohort eligible for mechanical thrombectomy but untreated due to unavailability or inability to initiate endovascular treatment within the 8-hr window due to delayed presentation. The goal is to compare the functional independence rate with the PROACT placebo group.

Methods:
The FIRST Trial is a prospective, multicenter, natural history study of a stroke cohort eligible for but untreated by mechanical thrombectomy presenting within 8 hrs of symptom onset from a large vessel occlusion and a NIHSS of at least 10. The primary endpoint is functional outcome at 90 days as defined by a mRS 0-2. Results are reported from an interim analysis.

Results:
Fifty-nine (59) patients were enrolled and met study criteria for this interim analysis. The mean age was 68.2 ± 17 years; median NIHSS was 18 (5-34). Target vessel occlusions were in the ICA (35.7%), MCA (60.7%), and other (3.6%). At admission, the TIMI 0-1 rate was 89% (49/55), and the TICI 0-1 rate was 89% (48/54). Of these, only 10% (3/30) showed spontaneous recanalization (TIMI 2-3 or TICI 2a-3). Eleven of 55 (20%) patients achieved a good 90-day outcome, and 24 of 59 (40.7%) died. The serious adverse event rate was 52.6% (30/57), including respiratory failure (8 cases) and pneumonia (4 cases). A total of 6 (10%) patients suffered intracerebral hemorrhage (ICH). Below is a comparison of the MCA cohort vs. PROACT II placebo patients.

Conclusion:
Compared with PROACT II placebo patients, the stroke cohort eligible for mechanical thrombectomy who were untreated have a lower rate of recanalization and worse outcome. These results indicate it may not be appropriate to use the PROACT placebo patients as historical controls for mechanical thrombectomy trials.
Abstract 26: Thirty Day And Six Month All-cause Mortality After Stroke In Patients With And Without Dysphagia Screening.
Authors: Hemmen Thomas M , Raman Rema , Ernstrom Karin , Paulson Debra , Lake Valerie , Snyder Andrea G , Hemmen Eema
Published: July 2021

Background:
Dysphagia is common after stroke and is associated with an increased risk for pulmonary complications

and mortality.

Current standards mandate screening for dysphagia before oral intake in all acute stroke patients. We aimed to show if this early screening affects long-term outcomes after stroke.

Methods:
We included all UCSD Medical Center discharges with diagnosis AIS, ICH and SAH between July 1 2008 and June 30 2011; and evaluated baseline demographics, admission diagnosis (AIS, ICH, SAH), admission source (ED or transfer) length of hospital stay (LOS), ICU-LOS, aspiration pneumonia, in-hospital, 30-day and 6-month mortality by public death records for all patients. Patients were grouped as: 1) no dysphagia screening performed, 2) Nil per os (NPO) until discharge, 3) dysphagia screening performed. Adjustments for stroke severity and CMI were not possible. Statistical comparisons were done with the Kruskal-Wallis test (continuous variables) or Fisher-Freeman-Halton test (categorical variables). For pairwise comparisons we used the Wilcoxon tests (continuous variables) or Fisher’s Exact test (categorical variables), with Holm’s adjusted p-values.

Results:
A total of 476 patients were included, Group 1: 47, Group 2: 119, Group 3: 310. There was no significant difference in age, gender, race/ethnicity, and diagnosis of HTN, DM, afib, prior stroke and admission source. More patients with SAH and ICH were in Group 2. Overall, LOS and ICU LOS, aspiration pneumonia, in-hospital, 30-day and 6-month mortality were found to be different among groups (p<0.0001). Pair-wise comparisons showed that all outcomes were significantly higher in Group 2, but similar between Groups 1 and 3 (NS).

Conclusion:
We found no difference in outcomes between patients who received dysphagia screening versus not (Group 1 vs 3). Excluding patients who were left NPO and are more likely to suffer from ICH, SAH with increased morbidity and mortality, it remains uncertain if a targeted early dysphagia screening can reduce morbidity and mortality after stroke. Further studies are needed to find the appropriate population that most benefits from dysphagia screening.
Abstract 62: Refining Angiographic Biomarkers of Reperfusion: Modified TICI Is Superior to TIMI for Predicting Clinical Outcomes After Intra-arterial Therapy
Authors: Yoo Albert J , Simonsen Claus Z , Prabhakaran Shyam , Chaudhry Zeshan A , Issa Mohammad , Fugate Jennifer E , Linfante Italo , Kallmes David F , Dabus Guilherme , Zaidat Osama O
Published: July 2021

Background:
Tissue reperfusion is a critical determinant of outcomes after intra-arterial therapy (IAT). However, there is no standardized method for grading angiographic reperfusion. We sought to compare the two most commonly used reperfusion scales, TIMI and modified TICI (m-TICI), for predicting good long-term outcome following IAT.

Methods:
From a multicenter database, we evaluated acute stroke patients presenting with middle cerebral artery (MCA) M1 occlusions who underwent IAT. Clinical and angiographic data were collected. Reperfusion for each case was graded using the TIMI and m-TICI scales. The primary distinction between these scales is that partial reperfusion (TIMI 2) is sub-divided into minor (m-TICI 2A: <50%) and major (m-TICI 2B: 50-99%) grades in the m-TICI system. The performance of these scales for predicting a good 90-day outcome (mRS 0-2) was evaluated using the c-statistic.

Results:
There were 313 acute stroke patients with MCA M1 segment occlusions who underwent IAT at 6 academic centers; 171 (54.6%) were female. Mean age was 65.3±16.5 years. There were 157 (50.2%) right-sided strokes. Median baseline NIHSS score was 17 (IQR 15-20). Good outcome at 90 days was achieved in 32.5%. For predicting good outcome, the c-statistic was significantly higher for m-TICI (0.74 vs. 0.68; p<0.0001). The threshold that maximized predictive accuracy was m-TICI ≥2B (sensitivity 78%, specificity 65%; figure).

Conclusions:
The modified TICI scale is superior to the TIMI scale for predicting clinical outcome after IAT, and should be the standard tool for grading angiographic reperfusion. An m-TICI score ≥2B (≥50% reperfusion) is the optimal biomarker for successful reperfusion.
Abstract NS1: Creating partnerships through the Kansas Initiative for Stroke Survival (KISS)
Authors: Sandt Janice , Brown Sarah E , Lechtenberg Colleen , Boxberger Cherie
Published: July 2021

Background and Purpose:
Kansas is a rural state lacking geographically distributed Primary Stroke Centers. Of the 128 hospitals in the state, 88 are designated as Critical Access (< 25 beds). The IV r-tPA treatment rate in the state of Kansas is less than 2%. The pre-transport death rate for patients experiencing stroke is 55.4% .The Kansas Initiative for Stroke Survival (KISS) is a non-government task force with the goal of improving stroke survival among Kansans. The task force encourages hospitals to meet the criteria as Emergent Stroke Ready and based on this status engage with their individual communities, emphasizing the need to seek immediate assistance by EMS and arrive at the closest Emergent Stroke Ready hospital.

Methods:
The Kansas State Stroke Task force determined requirements for a facility to be considered Emergent Stroke Ready. This information was distributed to all acute care hospitals, asking them to attest to their current Emergent Stroke Ready status. Responding facilities were provided access to a 24 x 7 Stroke Support Line - providing access to stroke specialists for the purpose of guiding evaluation and treatment decisions for r-tPA administration or need to transfer to a higher level of care. Also provided is a community education kit. Data is reported through a monthly online survey or GWTG database.

Results:
In the first phase of the KISS project - forty-two hospitals attested as Emergent Stroke Ready Hospital or were certified Primary Stroke Centers representing an increase from 7% to 33% of hospitals in the state. The post-KISS implementation IV r-tPA treatment rate for the reporting Emergent Stroke Ready Hospitals was 48% compared with a pre-KISS treatment rate of 6%. The post-KISS implementation transfer rate was 26.7% compared with a pre-KISS transfer rate of 18%.

Conclusions:
The KISS program resulted in a significant increase in the number of Emergent Stroke Ready facilities, stroke patients reporting to their local hospitals, stroke specialist consultations and use of IV r-tPA. A low-cost, statewide program that provides standardized protocols and direct phone consultation can improve access to stroke specialists and approved stroke treatment while offering a cost effective, feasible alternative to telestroke.
Abstract NS3: Code Stroke Interventional Radiology: Streamlining Processes For Expedited Patient Identification And Door To Groin Puncture Time
Authors: Schlegel Sherene , Likosky William , Gabelein Chad , Nord Stuart
Published: July 2021

Building on the success of Code Stroke as well as Code STEMI, we embarked on a journey to develop CODE STROKE IR for the streamlined delivery and appropriate identification of patients that may benefit from neuro-interventional therapies. Baseline data demonstrated our door to groin timeframe exceeded two and half hours as a result of undefined roles and responsibilities and the lack of a coordinated approach. We created a taskforce comprised of stroke team clinicians, analyst, neuro-interventionalists, as well as stakeholders from pharmacy, lab, ED, radiology, ICU and nursing.

Implementation strategies comprised mapping ideal workflow, identification of expected timeframes, algorithm development, staff training, mock drills and data review. Additionally we recognized a need to collaborate with our telestroke partners and transport agencies to assure clear communication and expedited transport of the patient to our organization. For appropriate patient selection, we included in our algorithm CT or MR diffusion perfusion mismatch and angiographic confirmation of occlusion.

Since the implementation of CODE STROKE IR in June 2011, we have been able to execute a well-choreographed streamlined approached to appropriately identify neuro-interventional rescue patients. Over 13 months we had 33 CODE STROKE IRs, of which 18 were identified as rescue candidates and proceeded to intervention. Our median door to groin time is now 89 minutes and we have a best practice of 63 minutes. Strategies to improve our processes are ongoing and consist of prompt review of each case followed by concurrent feedback to involved staff, reeducation of roles, and modification of workflow as indicated.
Abstract NS5: Pre-diabetes in the Reasons for Geographic and Racial Differences in Stroke Study: A Disregarded Stroke Risk?
Authors: Lee Loretta T , Alexandrov Anne W , Howard George , Howard Virginia J
Published: July 2021

Background:
Pre-diabetes is a new diagnostic category that is highly associated with a future diagnosis of diabetes. Given the risk for stroke associated with diabetes, we sought to determine bio-behavioral factors associated with pre-diabetes in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

Methods:
Participants who were normoglycemic (15,121) and pre-diabetic (4,768) were included. Logistic regression was used to assess the association of bio-behavioral factors (smoking, alcohol use, physical activity) and prevalence of pre-diabetes.

Results:
The analysis cohort was 36% African American and 64% White, with more Whites (67%) living within the Stroke Belt. Mean age of subjects was 64.5 + 10 years. The odds of having pre-diabetes as an African American regardless of region was 1.28 (95% CI: 1.19-1.36) compared to Whites, while the odds of having pre-diabetes as an African American living in the Stroke Belt was 1.29 (95% CI: 1.21-1.38) . African Americans with pre-diabetes were less educated (p<.0001) and had lower income (p< .0001) than Whites overall, and those with pre-diabetes within the Stroke Belt were less educated (p< .0001) and had lower income (p< .0001) than their counterparts from other regions. A majority of pre-diabetes African Americans (69%) and Whites (53%) reported no alcohol use at all, as did a majority of pre-diabetes subjects living inside (63%) and outside (53%) the Stroke Belt. Almost one half did not report current or past smoking. Only a minority of participants reported participation in intense physical activity > 4 times/week. A higher perceived health status was reported among Whites and people living outside the Stroke Belt with pre-diabetes (p<.0001).

Conclusion:
African American race and living in the Stroke Belt region are associated with increased odds of pre-diabetes. Interventions that aim to prevent pre-diabetes, as well as those that minimize development of a subsequent diabetes diagnosis, may play an important role in reducing future stroke events.
Abstract NS6: Family History of Stroke: Invisibility of a Key Stroke Risk Factor among High Risk African Americans
Authors: Aycock Dawn M , Kirkendoll Kenya D , Coleman Kisha C , Albright Karen C , Alexandrov Anne W
Published: July 2021

Background & Purpose:
Young to middle aged African Americans (AA) are at greater risk for a first-ever stroke, severe neurologic disability, and stroke-related mortality, than Caucasians of similar age; however, it remains unclear what role a family history of stroke (FHS) plays in promoting adoption of healthier lifestyles in this cohort. The purpose of this study was to explore differences between rural Stroke Belt AA with a FHS (e.g. parent/grandparent/sibling) on modifiable stroke risk factors, knowledge, perceived threat and perceived control of stroke, and exercise behaviors to AA without a FHS.

Methods:
A cross-sectional study was conducted recruiting AA aged 19-54 from the Black Belt region of Alabama via a mobile health clinic. Participants’ perceptions, knowledge, exercise history/intent, physiologic data, and health history were recorded.

Results:
Participants (N=66) averaged 43.3+9.4 years, were 71% female, with at least 12 years of school (89%), and unemployed (62%). Common risk factors were insufficient exercise (76%), obesity (59%), hypertension (53%; blood pressure M=145+17.6/88.3+12.9), and cigarette smoking (38%). Participants with a FHS (n=33) did not differ on average number of risk factors compared to those without a FHS (FHS 2.8+1.4 vs. 2.2+1.5; t(64)= 1.73, p=.089), nor did they differ on physiologic data. However, participants with a FHS were more likely to report a history of hypertension (67%) compared to those without a FHS (33%; χ2 =4.93, p <.05). There were no significant differences between groups for knowledge of stroke risk factors, perceived threat and perceived control of stroke, or recent exercise performance, although participants with a FHS (3.4+1.2) had significantly lower future intentions to exercise compared to those without a FHS (3.9+0.8); t(64)=2.45, p<.05).

Conclusions:
Although FHS is a significant non-modifiable risk factor for stroke and was common in this young to middle-aged AA cohort, FHS did not drive perceived stroke risk, risk factor control, or current/future intentions to exercise. Identification of interventions designed to personalize FHS as a key stroke risk factor, while promoting lifestyle change and self-management, may play an important role in future primary stroke prevention.
Abstract TMP102: Robotic Assessment Of Proprioceptive Dysfunction In Children With Perinatal Stroke
Authors: Kirton Adam , Yajure Janice , Leah Ion , Roe Jamie , Scott Steve , Dukelow Sean
Published: July 2021

Objective:
Perinatal stroke causes most hemiplegic cerebral palsy. Sensory dysfunction has been ignored and objective measurement tools are limited. Robotic technology can quantify complex sensory function in adult stroke but has not been applied to kids.

Methods:
Children from the Alberta Perinatal Stroke Project had MR confirmed unilateral perinatal stroke and upper extremity functional deficit. A bilateral exoskeletal robot (KINARM) capable of testing planar upper limb movements in an augmented reality environment was employed. Primary robotic outcomes were 2 dimensional variability, shift, and contraction/expansion scores of a position-matching task (Figure). Blinded clinical measures of sensory function (touch, proprioception, graphesthesia, stereognosis) were scored. Matched controls (age/gender) were tested.

Results:
Five children (median 14 yrs, 3 male) with perinatal stroke (3 PVI, 2 arterial) were compared to 7 controls. Stroke children demonstrated marked impairment in position matching including variability (6.48±1.4 vs 3.89±0.7cm, p= 0.001) and shift (5.05±2.2 vs 2.00±1.3cm). Contraction/expansion ratios were also abnormal (0.56±0.27 vs 0.31±0.22; p=0.09). Clinical sensory scores were lower but correlated poorly with robotic measures and motor function. Assessments were well tolerated with no adverse events.

Conclusion:
Robotic quantification of proprioception is feasible in perinatal stroke. Sensitivity and quantification appear superior to clinical exam. Disordered proprioception is an under-recognized component of disability and a novel therapeutic target.
Abstract TMP17: Serial ASPECTS from Baseline to 24 Hours in SWIFT: A Novel Surrogate Endpoint for Revascularization in Acute Stroke
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:
ASPECTS on baseline imaging is a known predictor of outcome in acute stroke. Change on serial ASPECTS after revascularization at 24 hrs may provide an early biomarker of therapeutic success or failure. We analyzed ASPECTS on baseline and 24-hr imaging in SWIFT to determine prognostic value and identify subgroups with extensive injury after intervention.

Methods:
ASPECTS at baseline and 24 hrs was independently scored by 2 imaging experts (disagreements resolved by consensus) in all anterior circulation SWIFT cases, blind to all other trial data. ASPECTS score at baseline, at 24 hrs, and serial changes were analyzed with univariate and multivariate approaches.

Results:
138 patients (mean age 67 yrs (SD 12), 52% female, median NIHSS 18 (IQR 8-28)) with full data were studied. Baseline ASPECTS (n=139) was 0-7 in 30 (22%), 8 in 34 (25%), 9 in 42 (30%) and 10 in 33 (24%). 24-hr ASPECTS (n=139) was 0 in 25 (18%), 1-4 in 35 (25%), 5-7 in 35 (25%) and 8-10 in 44 (31%). Baseline ASPECTS of 0-7 was related to worse NIHSS (OR 1.176, p=0.006) and absence of CAD (OR 0.20, p=0.008). Lower 24-hr ASPECTS was related to worse baseline NIHSS (p=0.003) and higher baseline SBP (p=0.033). Interestingly, baseline ASPECTS was linked with Day 7/discharge NIHSS (p=0.008) and Day 90 mRS (p=0.066), yet not TICI 2b/3 reperfusion or hemorrhage. 24-hr ASPECTS was closely linked with these outcome variables (all p<0.01). Multivariate model showed higher 24-hr ASPECTS predicted good clinical outcome (Day 90 mRS 0-2): OR 1.67, p<0.001. Among patients with high baseline ASPECTS scores (8-10; n=109), dramatic infarct progression (decrease in ASPECTS ≥ 6 points at 24 hrs) was noted in 31/109 (28%). Predictors of dramatic infarct progression were higher baseline SBP (p=0.019), higher baseline blood glucose (p=0.133), and failure to acheive TICI 2b/3 reperfusion (p<0.001). Such patients had worse Day 90 mRS outcomes (mean mRS 4.4 vs. 2.7, p<0.001).

Conclusions:
24-hr ASPECTS provides better prognostic information than baseline ASPECTS. Predictors of dramatic infarct progression on ASPECTS are hyperglycemia, hypertension and nonreperfusion. Serial ASPECTS score change from baseline to 24 hrs predicts clinical outcome and may serve as a useful, early surrogate endpoint for thrombectomy trials.