bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 61: MR Perfusion to Determine the Status of Collaterals in Patients With Acute Ischemic Stroke: Look Beyond Perfusion Time-maps
Authors: Nael Kambiz , Knitter James , Doshi Amish , Mocco J , Naidich Thomas
Published: July 2021

Purpose:
Collateral flow is an independent predictor of reperfusion and infarct size in patients with acute ischemic stroke (AIS). MR perfusion time-maps show delayed perfusion but unable to differentiate antegrade from collateral flow if used alone. Using a multiparametric approach, we aimed to identify a perfusion biomarker that can represent the extent of collaterals in comparison to angiographic findings.

Methods:
AIS patients with MCA proximal occlusion who had baseline MRI and cerebral angiography included. MR perfusion data were processed by Bayesian method to generate arterial tissue delay (ATD) maps at thresholds of 2 & 6 seconds. The volume of delayed perfusion (Vol-ATD
2sec
), critical hypoperfusion (Vol-ATD
6sec
), and hypoperfusion (Vol-ATD
2sec-6sec
) in addition to corresponding rCBV and rCBF were calculated. Baseline angiography collaterals were dichotomized to poor (TICI ≤2a) or good collaterals (TICI≥ 2b). The association of perfusion biomarkers and status of collaterals was assessed by repeated measure of analyses and receiver operating characteristic (ROC) to determine the optimal parameters for predicting the status of collaterals.

Results:
In 37 patients included, 20 had good collaterals on cerebral angiography. After controlling for age, baseline NIHSS and infarct volume, multivariate logistic regression analysis identified rCBV (p=0.001) and hypoperfused volume (Vol-ATD
2sec-6sec
), but not rCBF, Vol-ATD
2sec
or Vol-ATD
6sec
, as independent predictors of good collaterals. ROC analysis showed AUC of 0.89 (sensitivity/specificity: 85%90%) for rCBV and AUC of 0.78 (sensitivity/specificity: 70%82%) for Vol-ATD
2sec-6sec
. Hypoperfused tissue volume (Vol-ATD
2sec-6sec
) x its rCBV, termed
hypoperfused tissue collateral index
, remained an independent predictor of good collaterals with improved diagnostic accuracy over each measure alone (AUC: 0.96, sensitivity/specificity: 91%100%).

Conclusions:
Multiparametric MR perfusion can be used to assess the status of collaterals in patients with AIS.
Hypoperfused tissue collateral index
defined as hypoperfused volume (Vol-ATD
2sec-6sec
) x rCBV is a new perfusion index with diagnostic accuracy of 96% compared to angiographic findings to predict status of collaterals.
Abstract 65: Restoration of Growth Differentiation Factor 11 Protects Against Stroke in Mice
Authors: Chauhan Anjali , Hudobenko Jacob , Patrizz Anthony , McCullough Louise D
Published: July 2021

Introduction:
GDF 11 is a member of the transforming growth factor β superfamily. Loss of GDF11 occurs with aging and declining levels correlate with several detrimental age-associated phenotypes in both peripheral tissues and brain. Restoration of GDF11 enhances neurogenesis and cognitive function in aged mice. Brain expression of GDF11 has not been investigated after stroke. Stroke differentially affects the elderly. In this work we examined the role of GDF11 in aging, stroke and its potential utility as a neuroprotective agent.

Methods:
Male C57/BL6NCrl young (2-3 months) and aged (19-21) mice were used. Brain GDF11 expression was evaluated in young and aged mice by western blot. Focal ischemia was induced with a transient middle cerebral artery occlusion (MCAO). Mice were randomly assigned into two groups and were subjected to 90 min MCAO. Group 1 received vehicle (phosphate buffered saline) and group 2 was administered rGDF11 (100 ug/kg., ip) at the onset of ischemia. In additional experiments, the efficacy of delayed treatment (3 h after ischemia) with rGDF11 was tested. These mice were subjected to a 60 min MCAO. Mice were euthanized after 24 hours and 7 days respectively and brains were harvested to estimate infarct area.

Results:
A significant decrease in brain GDF11 levels was observed in aged mice as compared to young (p<0.05). Additionally, a significant decline in brain GDF11 expression was observed after stroke at 24 hours vs. sham groups (p<0.05). A significant decrease in cortical and hemispheric infarct area was observed in the rGDF11 group (cortical 48.73±1.05; hemisphere 49.68±3.58) as compared to vehicle group (60.54±4.88; 61.35±6.03), when GDF was administered at the time of ischemia. Delayed treatment with rGDF11 also reduced infarct at 7 days.

Conclusions:
Brain GDF11 levels decline with age and after stroke. Supplementation with rGDF11 ameliorates stroke induced injury in young mice at 24h and 7 days. These finding suggest potential role of GDF11 in age and stroke. Restoration of age-related loss of GDF may be a viable therapy for stroke.
Abstract 84: The EQUITe Telestroke Study
Authors: Solenski Nina , Southerland Andrew , Shephard Timothy , McMurry Tim , Hillman Diane , Lawrence Nick , Faber Thomas , Sharp Meredith , Wibberly Katharine
Published: July 2021

Background:
Telestroke (TS) is well established, yet there is a lack of large-scale, outcomes data on TS effectiveness to improve acute treatment in rural systems of care. Specialist On Call © is the largest national provider of tele-emergency consults, with > 23,000 consults/yr.; 61% are acute stroke consults. Funded by a HRSA grant, we evaluated effectiveness of TS programs to improve access and timeliness of tPA treatment n the UVA Telestroke and SOC tele network of rural hospitals.

Methods:
Phase I: Rural hospitals were defined by OMB standards. Aggregated SOC data were pooled from 46 hospitals 2012-15; (4,462 consults). 73% of patient encounters (3,247) were t ischemic strokes (AIS); 19% (578) were tPA treated. Data were analyzed for demographics, NIHSS score, % patients treated tPA < 60 min, and % treated within 3 hrs. of LSN. Phase II: An online CEU/CME telestroke-presenter training program was designed to teach emergency staff clinical/technical skills to facilitate TS encounters. www.startelehealth.org/.

Results:
53% of AIS patients were ≥ 65 yo; 47% ≤ 65 yo. In AIS patients, NIHSS was 0-8 in 79%, 9-15 in 11%, and 16-40 in 9.6%. For tPA treated patients, NIHSS was 0-8 in 53%, 9-15 in 23 % and 16-40 in 25%. A total of 73.2% of tPA patients were treated 180 min from LSN. 16.8% of AIS patients received tPA within 4.5 hrs of LSN. DTN median time was 83 min. 22% received tPA ≤ 60 min DTN. Patient arrival to SOC call initiated was 44 min (median). Call to video consult was 20min for both AIS and tPA patients. Phase II: Stroke protocol packets are being piloted in rural TS hospitals, and online telepresenter training has been launched (in progress).

Conclusions:
This is the largest outcomes study of acute TS encounters in rural US hospitals. Treatment in AIS with tPA was high (19%) indicating increased access to acute tele-neurological expertise. Teleconsultation physician response time was rapid, while patient arrival to SOC call time was much longer. Work is needed to ensure better adherence to DTN < 60min in rural hospitals consistent with AHA-ASA GL. In Phase II, we will determine impact of TS education programs to improve timeliness of treatment (stroke-specific tele-presenter training & triage protocols) in comparison to control.
Abstract 87: Selective Serotonin Reuptake Inhibitors and Risk of Intracerebral Hemorrhage
Authors: Obeidat Ahmed Z , Sekar Padmini , Moomaw Charles J , Martini Sharyl R , Osborne Jennifer , Woo Daniel , Flaherty Matthew L
Published: July 2021

Background:
Selective serotonin reuptake inhibitors (SSRI) are widely used in the treatment of psychiatric disorders such as post-stroke depression. Some studies have reported an association between SSRI use and increased bleeding risk, including intracerebral hemorrhage (ICH). We evaluated this association in two large ICH case control studies. We also tested to see whether SSRI use potentiates the bleeding risk associated with warfarin use and prior ischemic stroke.

Methods:
ICH cases and controls from the Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) and Ethnic Racial Variations in ICH (ERICH) studies were combined in an unmatched case-control analysis. SSRI use and variables previously associated with ICH risk were tested in univariate and multivariate analyses. Interaction terms for SSRI use plus warfarin use and SSRI use plus prior ischemic stroke were included.

Results:
There were 4134 ICH cases with 303 pre-stroke SSRI users (7.3%) and 4945 controls with 419 SSRI users (8.5%). Results of the multivariate analysis are presented in the table. In univariate analysis, SSRI use was protective (OR 0.85, CI 0.73-1.00, p = .05), however in multivariate analysis this became non-significant. Although the combination of an SSRI and warfarin produced a higher point estimate for ICH risk than warfarin alone, the interaction term did not reach significance (p = .09). There was no interaction found for SSRI use plus history of ischemic stroke.

Conclusions:
In this large case control analysis, SSRI use was not associated with increased risk of ICH. We also failed to confirm an interaction between SSRI use, warfarin use, and ICH risk, although a modest effect cannot be excluded. While a history of ischemic stroke is a risk factor for ICH, SSRI use did not increase that risk.
Abstract 94: Increased P450 Aromatase Level in Post-menopausal Women After an Acute Ischemic Stroke
Authors: Manwani Bharti , Fall Pamela , Conway Sarah E , Roy-O'Reilly Meaghan , Friedler Brett , Dimauro Sharon , Capozzi Lori , McCullough Louise D
Published: July 2021

Background:
Ischemic stroke is a sexually dimorphic disease. Sex differences in stroke have been attributed to neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation have shown detrimental effects. The role of sex hormones in stroke is still a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests similar aromatase activity in response to brain injury, as increased aromatase expression is seen in ischemic penumbra in animals. Administration of aromatase inhibitors exacerbates damage in experimental stroke models. However, studies on sex steroids in humans are sorely lacking.
Objective of this study was to investigate the contributions of sex steroids to the etiology of sex differences in stroke
.

Methods:
253 patients admitted to Hartford Hospital for focal neurological deficit were consented for 24hour blood draw from symptom onset. Stroke was confirmed by CTscan/MRI brain. Patients with intracerebral or subarachnoid hemorrhage, age<56 years, were excluded from the study. Controls were patients with transient ischemic attack/seizure. ELISA was run for estradiol, testosterone &P450 aromatase levels in serum.

Results:
In age matched men & women, no difference in estradiol levels was seen. For testosterone, main effect of sex, F(1,3)=26,p<0.001 & sex by stroke interaction F(1,3)=4.7,p<0.03 was seen. There was a significant effect of stroke, F(1,3)=9.3,p<0.003 & sex by stroke interaction, F(1,3)=5.8,p<0.01 in aromatase levels (*).

Conclusions:
Aromatase levels increase in post-menopausal women after acute ischemic stroke.
This may indicate increased aromatase activity as testosterone levels also decreased as compared with controls. Local production of estradiol may occur in the injured female brain mediated by aromatase as seen in prior animal studies. Ongoing work will assess functional outcomes and correlation with hormonal levels.
Abstract 99: Computational Fluid Dynamics of CT Angiography in SAMMPRIS Reveal Blood Flow and Vessel Interactions in Middle Cerebral Artery Stenoses
Authors: Liebeskind David S , Scalzo Fabien , Woolf Graham W , Zubak Justin M , Cotsonis George A , Lynn Michael J , Cloft Harry J , Zaidat Osama O , Fiorella David J , Derdeyn Colin P , Chimowitz Marc I , Feldmann Edward ,   for the SAMMPRIS Investigators
Published: July 2021

Background:
Noninvasive fractional flow measures with CT angiography (CTA) have revolutionized cardiology, yet the complex anatomy of the cerebral circulation and boundary conditions challenge the study of intracranial atherosclerosis. We developed a framework for systematic computational fluid dynamics (CFD) of middle cerebral artery (MCA) stenosis with CTA in SAMMPRIS.

Methods:
A 3D geometric mesh was generated from CTA source images, followed by CFD processing in Ansys (ICEM, CFX) on a Cray supercomputer. Reference boundary conditions were applied with an ICA inlet and outlets at the ACA and distal MCA to yield quantitative maps of intraluminal pressure drops (ΔP or fractional flow), blood flow velocity (V) and turbulent kinetic energy (TKE) with wall shear stress (WSS) mapped along the arteries. CFD parameters were then compared with SAMMPRIS angiography variables.

Results:
Of 451 SAMMPRIS (70-99% symptomatic stenosis) subjects, CTA was acquired at enrollment in 41 MCA cases. CFD results were successfully attained in 30, limited by anatomy (e.g. across branch points) in 7/11 and poor CTA resolution in 4/11. Fractional flow (ΔP) across stenosis was mean 0.64 ± SD 0.33, with maximal stenosis velocity of mean 192 ± SD 101 cm/s and maximal WSS 0.36 ± SD 0.25 mm Hg.

SAMMPRIS angiography percent stenosis was unrelated to ΔP -0.163 (p=0.399), velocity 0.126 (p=0.514) or WSS 0.078 (p=0.689). Worse collateral blood flow grades were associated with larger ΔP (p=0.137), higher velocity (p=0.059), higher WSS (p=0.112). Asymmetric WSS with high and low regions on opposing arterial walls was measured in the post-stenotic segment in 25/30 (83%). TKE maps revealed focal increases in the post-stenotic region, yet not above abnormal thresholds based on arterial diameter.

Conclusions:
CTA CFD of intracranial atherosclerosis provides detailed noninvasive measures of hemodynamics.
Abstract NS10: Rapidly Improving Stroke Symptoms - To Treat or Not to Treat
Authors: Friedrich Sherri H , Alexandrov Anne
Published: July 2021

Background:
Acute changes in the NIHSS are common in patients with large artery ischemic stroke. Unfortunately, even small improvements in the NIHSS may be viewed as a reason not to treat with intravenous tPA (IVtPA) among emergency practitioners with less alteplase experience. We sought to quantify outcome of patients denied IVtPA due to NIHSS score change, in an effort to improve future treatment decisions by our emergency practitioners.

Methods:
A retrospective observational study was conducted using a cohort of acute ischemic stroke patients presenting to our community hospital in southern California between January 1, 2010 and December 31, 2013. All patients in the cohort were denied IVtPA treatment due to perceived "rapidly improving symptoms" suggestive of TIA. The cohort was assembled from our Get with the Guidelines database, with all data verified to validate data accuracy. Descriptive data as well as the NIHSS score prompting the decision against IVtPA, both NIHSS and mRS at discharge, and length of stay (LOS) were entered and analyzed using SPSS.

Results:
50 patients were identified for IVtPA non-treatment due to an NIHSS change; patients were 60% male and averaged 71.8
+
11.1 years age. Pre-morbid mRS median was 0. NIHSS median at time of reason not to treat was 3.5. While admission and discharge NIHSS were similar, discharge median mRS was significantly worse than premorbid mRS at 2 (p<0.001), with the majority of patients discharging disabled from their stroke. Length of stay averaged 3.4
+
2.5 days and did not differ by age, gender or stroke subtype, but was positively correlated with discharge NIHSS scores (r=.627; p<0.001) which accounted for 39% of the variance.

Conclusion:
Change in NIHSS score without total disability resolution is a poor predictor of neurologic outcome after stroke. Regularly sharing discharge outcomes of patients according to IVtPA treatment status may play an important role in changing treatment decision making behaviors among reluctant alteplase users.
Abstract NS8: Prevalence and Relating Factors of Sleep Disturbances at 3 Months Post Stroke
Authors: Choi-Kwon Smi , Suh Minhee , Kim Jong S.
Published: July 2021

Background:
Post-stroke sleep disturbances (PSSD) are common and associated with various adverse outcomes. However, PSSD in the subacute stages of stroke have been scarcely studied. We aimed to evaluate the characteristics of and the factors related to PSSDs in stroke patients 3 months post-stroke.

Methods:
A total of 199 patients were evaluated for PSSD at 3 months after stroke. The quality of nighttime sleep and excessive daytime sleepiness (EDS) were assessed using the Verran Snyder-Halpern sleep scale and Epworth Sleepiness Scale, respectively. Presence of motor dysfunction and post-stroke pain, post-stroke depression, fatigue, and social support were evaluated.

Results:
Eighty eight patients (44.2%) had poor quality of night time sleep. Twenty eight patients (14.4%) reported EDS. Poor quality of sleep was independently associated with depression (p = 0.044) and EDS (p = 0.041) whereas fatigue (p = 0.000) and poor nighttime sleep (p = 0.045) were independently associated with EDS. Post-stroke pain and social support showed no association with PSSD.

Conclusions:
We found that PSSD 3 month post-stroke is common. Although causality remained to be determined, depression and nighttime sleep disturbances were related, whereas fatigue and nighttime sleep disturbances were related to EDS.
Abstract TMP100: Hemicraniectomy for Malignant MCA Syndrome: A Review of Functional Outcomes in Two High Volume Stroke Centers
Authors: Male Shailesh , Tsivgoulis Georgios , Goyal Nitin , Boviatsis Efstathios , Pandhi Abhi , Chang Jason , Zand Ramin , Zompola Christina , Elijovich Lucas , Alexandrov Anne W , Malkoff Marc D , Hoit Daniel , Arthur Adam S , Alexandrov Andrei V
Published: July 2021

Background&Purpose:
Despite recent landmark RCTs showing significant survival and functional outcome benefits with HCT compared with medical therapy (MT) in patients with malignant MCA infarction (MMCAI), HCT rates have not substantially increased in the US. It is difficult for patients’ families to reconcile the wishes of the patient with the possibility of poor functional outcome. We sought to evaluate early outcomes in patients with MMCAI who were treated with HCT (cases) in comparison to patients treated with MT due to the perception of procedural futility by families (controls).

Subjects&Methods:
We evaluated in a retrospective cohort study design consecutive patients with acute MMCAI treated in two tertiary care centers during a seven-year period. Pre-treatment NIHSS, NIHSS at discharge and modified Rankin Scale (mRS) at three months were documented. Functional independence (FI) and survival without severe disability (SWSD) were defined as mRS of 0-2 and 0-4 respectively.

Results:
A total of 66 patients (37 cases and 29 controls) fulfilled the study inclusion criteria [mean age 59±15 years, 52% men, median admission NIHSS-score: 19 points (IQR: 16-22]. Cases were younger (51±11 vs 68±13 years; p<0.001) and tended to have lower median admission NIHSS than controls [18 (IQR:16-20) vs 20 (IQR: 18-23); p=0.072], but the two groups did not differ significantly (p>0.05) in terms of other baseline characteristics. The rates of FI and SWSD at three months were higher in cases than controls [16% vs 0% (p=0.031) & 62% vs 0% (p<0.001)], while three-month mortality was lower (24% vs 77%; p<0.001). Multivariate Cox regression analysis identified HCT as the most important predictor of lower risk of death at three months (HR: 0.02, 95%CI: 0.01-0.10; p<0.001).

Conclusions:
HCT is a critical and effective therapy for patients with MMCAI but cannot provide a gurantee of functional recovery. Refusal of HCT by medical decision makers is common and reflects the complexity of issues under consideration in terms of patient outlook beyond the reduction of mortality following acute MMCAI.
Abstract TMP101: Safety and Outcome of High Doses IV Milirinone in Subarachnoid Hemorrhage With Refractory Vasospasm
Authors: Alamri Abdullah S , Alturki Abdulrahman , Badawy Mohammad , Letourneau Justin , Lannes Marcelo , Angle Mark , Lo Benjamin , Teitelbaum Jeanne
Published: July 2021

Introduction:
Vasospasm causing delayed cerebral ischemia (DCI) remains a leading cause of morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH). Our previously reported series detailed the safety and efficacy of cardiac doses of milrinone in DCI. Since 2007, we have been treating refractory delayed cerebral ischemia (RDCI) with very large doses of IV milrinone. We report the safety and clinical effect of high-dose milrinone in aSAH with RDCI.

Methods:
Retrospective single center analysis of all patients treated between October 2014 and July 2015 for vasospasm refractory to the MNH protocol (RDCI). RDCI patients received a bolus and perfusion that were increased incrementally until resolution of signs. If 2 boluses and 2 increases in perfusion were unsuccessful, patients underwent angiogram for intra-arterial (IA) milrinone and possible angioplasty.

Results:
40 patients were admitted for acute aSAH. Vasospasm was diagnosed clinically in 26 (65%). Initial milrinone therapy included a loading dose of 6 mg and an infusion of 0.75 mcg/kg/min. Of these patients, 18 had RDCI and received boluses of up to 8mg IV with perfusions of up to 2.75 mcg/kg/min. The maximum cumulative daily dose of milrinone was 230mg. There were no adverse cardiovascular events due to the drug. Neurologic improvement was seen in 8/18 with large IV bolus and perfusion of milrinone. Ten patients required angiography; all received IA milrinone, and angioplasty was performed in 3. Modified rankin scale (mRS) ≤ 2 on discharge was achieved in 6 of the 8 patients who improved with high-dose IV milrinone alone, 2 of 3 patients undergoing angioplasty and 4 of the 7 patients receiving IA milrinone without angioplasty.

Conclusion:
High doses of IV milrinone were effective in a large proportion of our patients with vasospasm and RDCI after aSAH, and it was extremely safe. This treatment could be considered prior to angioplasty.
Abstract TMP108: Absence of Cortical Microvessel Spasm During Large Vessel Spasm Following Experimental Subarachnoid Hemorrhage
Authors: Short Kurt W , Church Ephraim W , Patel Akshal S , Cockroft Kevin M , Drew Patrick J
Published: July 2021

Introduction:
A significant portion of the morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH) is due to delayed ischemic neurological deficits (DIND). Although large vessel vasospasm has been implicated as a cause of DIND, the presence of such spasm is not always correlated with DIND. In the present experiment we examined the cortical microvasculature in awake mice after SAH in an experimental model typically associated with large vessel vasospasm.

Methods:
Twenty adult mice underwent cisterna magna (CM) injection of 60ul syngenic donor blood or artificial cerebrospinal fluid (aCSF). The mice were perfused at 72 hours, and Circle of Willis (COW) vessel diameters were measured. In a separate experiment, polished and reinforced thinned skull cranial windows were created in 10 mice that then underwent CM blood or aCSF injection. Cortical microvessels were measured in living, awake mice in the postoperative vasospasm period using two photon laser scanning microscopy.

Results:
A pairwise comparison of COW vessels revealed a statistically significant difference in vessel diameter between the experimental and control groups at each of the sites measured (ACA, P=0.0012; MCA, P=0.0259; Pcom, P=0.0053). In the second experiment, there were no significant differences in cortical microvessel diameter between the experimental and control groups.

Conclusions:
This study represents the first report of in vivo imaging of cortical microvessels during large vessel spasm following SAH. In a CM injection SAH model, we observed significant large vessel spasm but no cortical microvessel spasm. These results may have important implications for understanding the mechanisms of DIND.
Abstract TMP118: Increased Brain Derived Neurotrophic Factor (BDNF) and Vascular Endothelial Growth (VEGF) After Long Term Remote Ischemic Conditioning (RIC): Possible Role in Neurovascular Plasticity During Vascular Cognitive Impairment (VCI)
Authors: Khan Mohammad B , Vaibhav Kumar , Dhandapani Krishnan M , Hoda Md. N , Hess David C
Published: July 2021

Background and Purpose:
Vascular dysfunction and resultant chronic cerebral hypoperfusion leads to VCI, the second most common cause of dementia. We reported that RIC-therapy improves cerebral blood flow (CBF) in both murine stroke and VCI models. In the present work, we hypothesized that long-term RIC-therapy after VCI will promote neurovascular plasticity via up-regulation of growth factors.

Methods:
Microcoil induced bilateral common carotid artery (BCAS) model was used to induce chronic hypoperfusion. Adult C57BL/6J male mice of (10-weeks) were assigned to 3-different groups (N=6), and subjected to Sham- (procedures of BCAS and RIC), BCAS- (induced VCI followed by RIC-Sham), and BCAS+RIC (induced VCI followed by RIC-therapy). RIC was started 7d post-surgery for 2-wks. At 4-wks post-surgery (1-wk after the cessation of RIC) CBF was determined using laser speckle contrast imager (LSCI). Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire test for motor impairment. Histopathology as well as immunohistochemistry for BDNF and VGEF were also performed on the of the brain tissue collected after the neurobehavioral tests. Statistical significance was determined at p <0.05.

Results:
RIC-therapy significantly improved CBF in BCAS+RIC group compared to the BCAS group. Mice from the BCAS group showed significant loss in the discrimination index as determined by the NOR test, and poor motor function strength in hanging wire test. RIC-therapy in BCAS+RIC group significantly improved functional outcomes as compared to the BCAS-group. Histopathological studies clearly showed prevention of neurovascular degeneration by RIC. Interestingly, immunohistochemical analysis revealed loss in BDNF and VEGF expressions in the BCAS-group as compared to Sham that was increased in the BCAS+RIC-group.

Conclusions:
RIC-therapy attenuates neurovascular stress via improved CBF that attenuates neurovascular degeneration and prevents functional impairments. RIC increases BDNF and VEGF levels. Long term RIC-therapy could be a conventional therapy for aged individuals suffering from VCI and resultant motor impairment.
Abstract TMP120: Race and Sex Differences in the Trajectory of Cognitive Decline After Incident Stroke
Authors: Levine Deborah A , Galecki Andrzej T , Langa Kenneth M , Unverzagt Frederick W , Kabeto Mohammed U , Giordani Bruno , Howard George , Howard Virginia J , Cushman Mary , Judd Suzanne E , Wadley Virginia G
Published: July 2021

Background and Objectives:
Race and sex differences in the trajectory of survivors’ cognitive changes after stroke are uncertain. We measured changes in cognitive function associated with incident stroke and variability by race (black vs white) and sex, controlling for prestroke cognitive trajectories.

Methods:
Prospective study of 654 survivors of incident stroke and 22,969 stroke-free participants aged ≥45 years without baseline cognitive impairment from the REGARDS cohort enrolled 2003-2007 and followed through September 30, 2014. Median follow-up was 7.3 years. Changes in global cognition (Six-Item Screener [SIS]; range, 0-6; primary outcome), new learning, verbal memory, and executive function (Word-List Learning, Word-List Delayed Recall, and Animal Fluency Test) were measured using a regression discontinuity analytic approach, where the acute effect of stroke was estimated as the difference in the expected cognitive level on the day of the stroke from the modeled trajectory of cognitive functioning before the stroke and the trajectory of cognitive functioning after the stroke. These trajectories of post-baseline cognitive function were estimated after adjustment for calendar time and baseline values of socio-demographics, vascular risk factors, clinical factors, baseline cognitive score, and random effects for intercept and slope.

Results:
After stroke, acute declines in global cognition were greater in men compared with women (P=0.003) and also greater in blacks compared with whites (P=0.03) (Figure). Adjusted declines in SIS scores were 0.22 points (95% CI, 0.14 to 0.31) in black men, 0.13 points (95% CI, 0.06 to 0.20) in white men, 0.10 points (95% CI, 0.02 to 0.18) in black women, and 0.01 points (95% CI, -0.06 to 0.09) in white women. Secondary cognitive assessments did not differ significantly by race or sex.

Conclusion:
The acute declines in global cognition after stroke are greater in men compared with women and in blacks compared with whites.
Abstract TMP26: Cerebral Atrophy and Functional Outcome After Intensive Rehabilitation in Elderly Patients With Ischemic Stroke
Authors: Tanaka Makiko , Ito Taiji , Nakanaga Ayako , Sugiura Shiro , Shimizu Yoshiomi , Yoshikawa Kenji , Takahashi Tsutomu
Published: July 2021

Introduction:
Functional outcome after stroke is predicted to be unfavorable in patients with dementia. However, sometimes it is difficult to know prestroke cognitive function in patients with aphasia and other cognitive impairments.

Hypothesis:
Cerebral atrophy in patients without dementia is a predictive marker for functional outcome following intensive rehabilitation after ischemic stroke.

Methods:
In patients aged 65 years or older with acute ischemic stroke in our stroke center, those who were moved to a rehabilitation unit and underwent intensive rehabilitation for 1–3 months were selected. Patients with prestroke modified Rankin scale ≥ 2 or with diagnosed dementia were excluded. Severity of cerebral atrophy was assessed on axial brain MRI performed with routine protocols in an acute phase. Hippocampal atrophy, cortical atrophy, and subcortical atrophy were separately assessed using the visual rating scales. Functional status was measured using the Functional Independence Measure (FIM) scale after 2 weeks from onset (FIM 1), when a patient was moved to a rehabilitation unit (FIM 2), and at the time of discharge (FIM 3). We retrospectively investigated the association between cerebral atrophy and FIM scores.

Results:
In a total of 197 patients (119 men and 78 women; median age, 74 years), the average time interval between stroke onset and transfer to the rehabilitation unit was 33.8 days and the length of stay in the unit was 58.7 days. FIM 1–3 scores were strongly associated with age, initial stroke severity, and cerebral atrophy. In the multivariate analyses, subcortical atrophy was significantly associated with FIM 1 (P=0.02), FIM 2 (P=0.003) and FIM 3 (P=0.008), and hippocampal atrophy was associated with FIM 3 (P=0.01) but not with FIM 1 and FIM 2 after adjusting for age, sex, stroke severity, and rehabilitation periods. Cortical atrophy was not associated with FIM scores after adjusting for age and other related factors.

Conclusion:
In elderly patients without apparent dementia, subcortical atrophy and hippocampal atrophy assessed on axial brain MRI with simple visual ratings were remarkable predictors of poor functional outcome after ischemic stroke.
Abstract TMP27: How Generalizable are Rehabilitation Trials? The Results of a Large International Rehabilitation Trial (AVERT)
Authors: Bernhardt Julie , Raffelt Audrey , Churilov Leonid , Lindley Richard I , Speare Sally , Ancliffe Jacqueline , Katijjahbe Md Ali , Hameed Shahul , Lennon Sheila , McRae Anna , Tan Dawn , Quiney Jan , Williamson Hannah C , Collier Janice , Dewey Helen M , Donnan Geoffrey A , Langhorne Peter , Thrift Amanda G ,   on behalf of the AVERT Trialists' Collaboration
Published: July 2021

Introduction:
Generalizability of the results of randomized controlled trials (RCTs) could be compromised when recruitment is poor. We aimed to examine potential threats to generalizability of a multicenter RCT using data from A Very Early Rehabilitation Trial (AVERT).

Methods:
AVERT is a prospective, parallel group, assessor-blinded, randomized, clinical trial. The trial setting is acute stroke units at 44 hospitals in 8 countries. Among the first 20,000 patients screened for AVERT, 1158 were recruited and randomized. We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalizability. As well as comparing the recruited patients to the target population, we performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment.

Results:
The demographics and stroke characteristics of the included patients in the trial were broadly similar to population based norms, with the exception that men featured more often in those recruited (63%) than not recruited (53%, p<0.001). The most common reason for non-recruitment was late arrival to hospital (i.e. >24 hours). Overall, being older and female reduced the odds of recruitment to the trial. More women than men were excluded for most of the reasons, including refusal. The odds of exclusion due to early deterioration were particularly high for those with severe stroke (OR=10.4, p<0.001, 95%CI: 9.27–11.65).

Conclusions:
A model which explores person, place and setting and practice factors can provide important information about the external validity of a trial, and could be applied to other clinical trials.
Abstract TMP3: Low Concentration Normobaric Oxygen Enhanced Therapeutic Effect of Mild Hypothermia or Ethanol Through a Reduction in Apoptosis
Authors: Liu Kaiyin , Cai Lipeng , Peng Changya , Geng Xiaokun , Ji Xunming , Guthikonda Murali , Ding Yuchuan
Published: July 2021

Introduction:
Neuroprotective effects of normobaric oxygen (NBO) and ethanol (EtOH) has been shown. In a clinically relevant autologous embolus rat stroke model in which reperfusion was established by tissue-type plasminogen activator (rt-PA), the present study further evaluated whether low concentration NBO enhanced therapeutic effect of mild hypothermia (Hypo) or EtOH through a reduction in apoptosis and whether EtOH can substitute for hypothermia.

Hypothesis:
Hypo and EtOH has been shown to have neuroprotective effects through similar mechanisms. We assessed the hypothesis that low concentration NBO, whose neuroprotective effects are currently debated, has benefit in our stroke models, and we further assessed the hypothesis that EtOH can substitute for Hypo in the presence of tPA and NBO.

Methods:
At 1 hour of middle cerebral artery occlusion (MCAO) by an autologous embolus, rats (96 total, 12 in each treatment group) received rt-PA and other treatments of either EtOH (1.0 g/kg) or Hypo (33 °C for 3 hours) in combination with NBO (60% for 3 hours). Apoptotic cell death was measured by ELISA. Western immunoblotting was performed for pro- (AIF, Caspase-3, Bax) and anti-apoptotic (Bcl-2) protein expression at 3 and 24 hours of reperfusion.

Results:
Compared to ischemic rats treated only with rt-PA, animals with NBO, hypothermia or EtOH had significantly reduced apoptotic cell death by 32.5%, 43.1% and 36.0% respectively. However, combination therapy that included NBO+EtOH or NBO+Hypo with rt-PA exhibited a much larger decline (p<0.01) in the cell death by 71.1% and 73.6%, respectively. Similarly, NBO+EtOH or NBO+Hypo treatment in addition to rt-PA enhanced beneficial effects on both pro- and anti-apoptotic protein expressions as compared to other options.

Conclusions:
Neuroprotection after reperfusion with rt-PA in ischemic stroke induced by thromboembolism are enhanced by combination treatment with either EtOH or Hypo in the presence of 60% NBO through reduced apoptosis. Since the effects produced by EtOH and Hypo are comparable, their mechanism of action may not only be similar but also could be interchangeable. Since EtOH administration does not lead to temperature decrease, EtOH may a better alternative than Hypo.
Abstract TMP35: Higher Predicted Aerobic Fitness is Related to Above Median Insulin-like Growth Factor 1 in Individuals With Acute Stroke
Authors: Mattlage Anna , Rippee Michael , Sandt Janice , Billinger Sandra A
Published: July 2021

Background:
In healthy individuals, higher circulating insulin-like growth factor-1 (IGF-1) is related to higher aerobic fitness, measured as peak VO
2
. IGF-1 has been shown to possess neuroprotective qualities after stroke. Prior work suggests that elevated IGF-1 within the first week of stroke lead to increased survival rates and less severe stroke impairments at one month. However, it is unclear whether higher aerobic fitness is related IGF-1 levels after stroke. It is difficult to measure peak VO2 during the acute hospital stay. However, using a previously established peak VO2 prediction equation would allow us to address this gap in knowledge. By understanding the interaction of IGF-1 and estimated peak VO
2
after stroke, knowledge can be gained in people post-stroke. We hypothesize that individuals with acute stroke and above median levels of IGF-1 will have significantly higher estimated peak VO
2
at the time of admission.

Methods:
Twenty-two individuals (10 male; 61 ± 11 years of age) with a diagnosis of acute stroke were enrolled into our study. Blood was sampled within 72 hours of hospital admission under fasting conditions between the hours of 7:30 and 9 am. Samples were centrifuged to obtain plasma, aliquotted, and frozen until assaying. Standard ELISA analyses were used to quantify total IGF-1. Upon enrollment, peak VO
2
was estimated using a previously established equation that considered a self-report measure of physical activity level, age, gender, BMI, and resting heart rate.

Results:
Median level of IGF-1 was 121 ng/mL. Those who had above median levels of IGF-1 had significantly higher estimated peak VO
2
(29.8 ± 7.9 ml/kg/min) compared to those with lower than median IGF-1 levels (20.9 ± 7.6 ml/kg/min; p = .014).

Conclusion:
Our data suggests that being physically active prior to stroke and possessing a higher estimated peak VO
2
may have higher IGF-1 levels in individuals after stroke. This may provide some neuroprotective benefit. Future trials with a larger sample size are needed to determine if higher IGF-1 is related to measured aerobic fitness after stroke.
Abstract TMP38: Vertebrobasilar Dolichoectasia is a Distinct Subtype of Intracranial Large Artery Disease: Computational Fluid Dynamics of Hemodynamic Abnormalities
Authors: Liebeskind David S , Woolf Graham W , Zubak Justin M , Scalzo Fabien , Sanossian Nerses
Published: July 2021

Background:
Imaging of stroke due to vertebrobasilar dolichoectasia may not reveal either luminal stenosis or atherosclerotic plaque, leading to misdiagnosis of stroke mechanism or etiology. We leveraged the advanced imaging capabilities of computational fluid dynamics (CFD) to disclose the hemodynamic abnormalities within these complex neurovascular lesions.

Methods:
CT angiography from a series of stroke patients with vertebrobasilar dolichoectasia was selected from a prospective imaging registry of posterior circulation ischemia. A 3D geometric mesh was generated from CTA source images, extending from distal V4 vertebral arteries (VA) to the P1 posterior cerebral arteries (PCA). CFD processing was conducted with Ansys (ICEM, CFX) on a Cray supercomputer. Boundary conditions applied at the VA inlets and PCA outlets were used to map intraluminal pressure changes (ΔP), blood flow velocities (V), turbulent kinetic energy (TKE) and wall shear stress (WSS).

Results:
18 cases of vertebrobasilar dolichoectasia with CTA source images were processed with CFD. Focal stenoses (>50%) were apparent in only 4/18 (22%) cases.

Intraluminal pressure varied markedly throughout the vertebrobasilar arterial segments in 7/18 (39%) cases. Blood flow velocities were also heterogeneous, with increases in 6/18 (33%) cases and decreases in 5/18 (28%) cases. WSS was markedly abnormal in all 18 cases, revealing regions of both elevated WSS and contralateral decreases in WSS. Maximal TKE values were within expected range for arterial diameter, yet obvious eddy currents were visualized in all 18 cases.

Conclusions:
CFD generated from routine CTA reveals numerous hemodynamic abnormalities in vertebrobasilar dolichoectasia, even when stenosis is unapparent. WSS-induced remodeling mapped with CFD may be used to detect arteriogenesis and atherosclerotic lesion development.
Abstract TMP40: Impact of Age on Atrial Fibrillation Detection among a Large, Real-World Population of Cryptogenic Stroke Patients with Insertable Cardiac Monitors
Authors: Richards Mark , Rogers John D , Ferreira Scott W , Nichols Allan J , Koehler Jodi L , Sarkar Shantanu , Ziegler Paul D
Published: July 2021

Introduction:
Detection of atrial fibrillation (AF) in patients with a cryptogenic stroke (CS) is critical for reducing the risk of recurrent stroke by enabling oral anticoagulation therapy. However, the impact of age on AF detection and the optimum duration of AF monitoring in patients following a CS is not well characterized. We investigated the impact of age on AF detection among a large, real-world cohort of unselected patients with an implantable cardiac monitor (ICM) placed following CS.

Methods:
Patients in the de-identified Medtronic Discovery™ Link database who received an ICM (Reveal LINQ™) for AF detection following CS were included and monitored for up to 182 days. All AF episodes were adjudicated. We compared the mean age between patients with vs. without AF detected and compared the median time to detection of the first AF episode between younger (age ≤65) and older (age >65) patients.

Results:
Among 1247 patients (mean age 65.3±13.0, 53% male) followed for 182 [IQR 182-182] days, 1521 AF episodes were detected in 147 patients and resulted in an AF detection rate of 12.2%. Patients with AF detected were significantly older than patients without AF detected (71.3±10.9 vs. 64.5±13.1 years, respectively; p<0.001). The median time to detection of the first AF episode was shorter for older vs. younger patients (43 [10-91] vs. 89 [29-127] days, respectively; p=0.016; Figure).

Conclusion:
Continuous monitoring of CS patients with an ICM resulted in an AF detection rate of 12.2% within the initial 6 months. Patients with AF detected were older and patients >65 years of age had shorter times to initial AF detection. However even among older patients, the majority of AF occurred outside the range of external monitoring devices and thus highlights the importance of long-term monitoring with ICMs in the management of CS patients.
Abstract TMP42: Distinguishing Clinical and Radiologic Features of Non-Traumatic Convexal Subarachnoid Hemorrhage
Authors: Graff-Radford Jonathan , Fugate Jennifer , Klaas James , Flemming Kelly , Brown Robert , Rabinstein Alejandro
Published: July 2021

Introduction:
Small case series have suggested that cerebral amyloid angiopathy (CAA) and reversible cerebral vasoconstriction syndrome (RCVS) are the most common causes of non-traumatic convexal SAH (cSAH). Our objective was to describe the spectrum of clinical and imaging features in a large series of non-traumatic cSAH patients.

Methods:
A retrospective observational study of consecutive patients with non-traumatic cSAH was performed. The Mayo Clinic Medical Records Linkage system was used to identify all patients evaluated at Mayo Clinic in Rochester with potential non-traumatic cSAH between January 1, 1996 and October 1, 2014. Clinical and radiologic data were abstracted from the comprehensive medical record.

Results:
We identified 88 patients [median age, 64 years (range: 25-85)] with non-traumatic cSAH. The most common causes were reversible cerebral vasoconstriction syndrome (26, 29.5%), cerebral amyloid angiopathy (23, 26.1%), indeterminate (14, 15.9%), and endocarditis (9, 10.2%). Other causes include posterior reversible encephalopathy syndrome, cerebral vein thrombosis, vasculitis, carotid occlusive disease, thrombosed developmental venous anomaly, and hyperperfusion syndrome after carotid revascularization. CAA patients commonly presented at an older age than RCVS patients (75 years vs 51 years, p<0.0001). The most common clinical presentation for CAA was sensorimotor dysfunction while thunderclap headache was the most common presentation of RCVS. Thirteen patients (14.7%) had recurrent cSAH and twelve patients (13.6%) had a subsequent intracerebral hemorrhage over a median follow up of 16 months. The risk was high among CAA patients, with subsequent lobar ICH occurring in 43.5% of cases, superficial siderosis in 95%, and recurrent cSAH in 39.1%, compared to 3.8%, 28.5% and 7.7% respectively in RCVS.

Conclusions:
Our study demonstrates the clinical diversity of cSAH. Older age, sensorimotor dysfunctions suggest CAA as the underlying cause. Younger age and thunderclap headache predict RCVS. Various other causes also need to be considered in the differential diagnosis. CAA patients have high rates of subsequent lobar ICH, development of superficial siderosis, and recurrent cSAH.
Abstract TMP5: Secondary Analysis of Eptifibatide Plus Full Dose rt-PA in Ischemic Stroke
Authors: Adeoye Opeolu , Sucharew Heidi , Khoury Jane , Schmit Pamela , Broderick Joseph , Pancioli Arthur
Published: July 2021

Background:
The Phase 2 Combined approach to Lysis utilizing Eptifibatide And Rt-PA in Acute Ischemic Stroke - Full Dose Regimen (CLEAR-FDR) trial was a single arm trial that demonstrated the safety of full dose (0.9mg/kg) rt-PA plus eptifibatide in AIS patients treated with rt-PA within three hours of symptom onset. Interventional Management of Stroke (IMS) III randomized AIS patients to rt-PA plus endovascular therapy versus standard r-tPA. Albumin in Acute Stroke (ALIAS) Part 2 randomized patients to albumin±rt-PA versus saline±rt-PA. We compared outcomes in CLEAR-FDR patients to propensity score-matched rt-PA only subjects in ALIAS Part 2 and IMS.

Methods:
All datasets were restricted to subjects with baseline modified Rankin score (mRS) of 0 or 1. Controls were selected using propensity score matching of CLEAR-FDR subjects and rt-PA only subjects from both IMS III and ALIAS. Age, gender, race, baseline mRS, baseline NIHSS score, and time from stroke onset to rt-PA were included in the logistic model used to generate a propensity score for each subject. The greedy matching algorithm was then used to match 1:3. The primary outcome was 90-day severity-adjusted mRS dichotomization based on baseline NIHSS. Secondary outcomes were 90-day mRS dichotomized as excellent (mRS 0-1); favorable (mRS 0-2); and, nonparametric analysis of the ordinal mRS.

Results:
Eighteen CLEAR-FDR subjects were matched with 52 controls. Median age in CLEAR-FDR and control subjects was 67 and 68 years respectively. Median NIHSS in both CLEAR-FDR and control subjects was 11. At 90 days, CLEAR-FDR subjects had a nonsignificant greater proportion of patients with a favorable primary outcome (61% versus 38%; unadjusted RR 1.59; 95%CI 0.96-2.63; P=0.10). Secondary outcomes also favored CLEAR-FDR subjects: excellent outcomes - 67% versus 38% (RR 1.73; 95%CI 1.08-2.79; P=0.04); favorable outcomes - 67% versus 58% (RR 1.16; 95%CI 0.77-1.73; P=0.50); and ordinal Cochran-Mantel-Haenszel, P=0.13.

Conclusion:
The outcomes for combination of full dose rt-PA plus eptifibatide showed a consistent direction of effect in favor of the combination over rt-PA alone. A trial to establish the efficacy of rt-PA plus eptifibatide for improving AIS outcomes is warranted and in the planning stages.