bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2559: Subgroup analysis of the Cilostazol Stroke Prevention Study 2 (CSPS 2)
Authors: Uchiyama Shinichiro ,   for the CSPS 2 Group
Published: July 2021

Background:
Cilostazol has been suggested to be superior to aspirin in secondary stroke prevention in patients with non-cardioembolic ischemic stroke from the results of the CSPS 2 and meta-analysis of the Cochrane Collaboration. The purpose of this study was to investigate the efficacy and safety of cilostazol and aspirin in the various subgroups of the study population.

Methods:
Recurrence of stroke was studied in the subgroup analysis according to patient's characteristics, concomitant use of drugs, and ischemic stroke subtypes. Heterogeneity of stroke risk between subgroups classified by each variable was analyzed using Log-rank test.

Results:
A total of 2672 Japanese patients enrolled in the CSPS 2 (Lancet Neurol 2010;9:959-68) were analyzed. A tendency of interaction was observed in alcohol drinking (p=0.0782) and dyslipidemia (p=0.0873). Stroke rates in alcohol drinkers (HR 0.574, 95% CI 0.386-0.855) and non-dyslipidemic patients (HR 0.608, 95% CI 0.426-0.869) were lower in the cilostazol group than in the aspirin group. A significant interaction was demonstrated in the use of angiotensin receptor blocker (ARB) (p=0.0267). Stroke rate in non-users of ARB was lower in the cilostazol group than in the aspirin group (HR 0.542, 95% CI 0.370-0.793), while it was not different between both groups in users of ARB (HR 1.016, 95% CI 0.677-1.524). There was no significant difference in the rate of ischemic stroke between both treatment groups in patients with atherothrombotic stroke (cilostazol 1.77%/year, aspirin 2.45%/year, p=0.2808) and lacunar stroke (cilostazol 2.68%, aspirin 2.88%/year, p=0.7198). The rate of hemorrhagic stroke was not different between both groupsin patients with atherothrombotic stroke (cilostazol 0.31%/year, aspirin 0.59%/year, p=0.3444), while it was significantly much lower in the cilostazol group (0.36%/year) than in the aspirin group (1.20%/year) (RRR 65.0%, p=0.0030) among patients with lacunar stroke.

Conclusion:
Superiority of cilostazol over aspirin in secondary stroke prevention tended to be more obvious in alcohol drinkers and non-dyslipidemics. A significant interaction was observed in the concomitant use of ARB, which might be related to pleiotropic effects of cilostazol and ARB. Cilostazol has an advantage over aspirin in lower risk of cerebral hemorrhage especially in Japanese patients with lacunar stroke.
Abstract 2568: Cerebral Infarcts in Blacks vs Whites: the Southall and Brent REvisited (SABRE) Multi-ethnic Cohort Study
Authors: Shibata Dean , Tillin Therese , Beauchamp Norman , Heasman John , Gedroyc Wadyslaw , Stewart Rob , Hughes Alun , Chaturvedi Nish
Published: July 2021

Introduction:
Stroke mortality is doubled in people of Black African descent compared with Whites, but factors responsible for this excess are unclear. We wished to compare infarct like lesions (ILL) on MRI by ethnicity and the role of risk factors.

Methods:
SABRE is a UK community based multi-ethnic cohort of men and women aged 40-69 years at baseline (1988-1990), and 58-86 years at follow up (2008-2011). At follow up, a questionnaire was completed and investigations performed including resting and ambulatory BP, anthropometry, and bloods for glucose and lipids. Cerebral MRI scans were scored for infarcts independently by two readers according to the Cardiovascular Health Study protocol.

Results:
Of 2346 Whites, 684 attended follow up, and 590 completed cerebral MRI. Of 801 Blacks (first generation migrants of Black African descent to the UK), 232 attended clinic and 207 completed MRI. Mortality loss was greater in Whites (605, 25%) than Blacks (121, 15%)(p<0.0001), although stroke was more likely the underlying cause in Blacks (23, 19%), than Whites (43, 7%)(p<0.0001) . Baseline systolic/diastolic BP was similarly higher in Blacks than Whites in attendees (8/5 mmHg), non-responders (7/6 mm Hg), and those who died (8/5 mmHg). At follow up stroke risk factors were adverse in Blacks, apart from smoking (
table
). Prevalence of ILL was similar by ethnicity, not differing when those <65 years were analysed separately, or when those with stroke/TIA history were excluded. Associations between ILL and risk factors did not differ by ethnicity. But prescribed treatment in those with elevated clinic BP (≥140 mmHg systolic, or ≥90 mmHg diastolic) was 83% in Blacks, 63% in Whites (p<0.0001). Further, in those with an ILL, 95% of Blacks, and 69% (p<0.0001) of Whites were on treatment.

Conclusion:
Equivalence of ILL rates in Blacks and Whites was unanticipated, given the greater stroke mortality in Blacks. Mitigating against selective mortality as the explanation of our findings is the similar ethnic differential in baseline BP in survivors and non-survivors, the lower overall mortality in Blacks, and overall small numbers of stroke deaths. A more likely explanation is that better targeted more aggressive treatment is now occurring in Blacks than Whites, reducing their potential burden of ILL.
Abstract 2589: Temperature Dependence of Lysis with Tissue Plasminogen Activator, Eptifibatide, and Ultrasound
Authors: Meunier Jason M , Bluett Brent , Wenker Evan P , Chang Wan-Tsu W , Shaw George J
Published: July 2021

Introduction:
Recombinant tissue plasminogen activator (rt-PA) is the only FDA approved thrombolytic therapy for acute ischemic stroke. Recent studies have shown hypothermia to be beneficial in patient outcome in stroke. However, rt-PA is less effective at temperatures less than 37°C. Interest in improving the lytic efficacy of rt-PA thrombolysis has led to the study of adjunctive therapies such as GP IIb-IIIa inhibitors like eptifibatide (Epf) and ultrasound (US) enhanced thrombolysis. However, the thrombolytic efficacy of combination therapy with rt-PA over a clinically applicable temperature range is unknown.

Objective:
The effects of temperature on the thrombolytic efficacy of combination rt-PA-driven thrombolysis were determined in an in-vitro human clot model.

Methods:
Human whole blood clots were made from blood obtained from volunteers, after local Institutional Review Board approval. Clots were made in 20-µL pipettes and placed in a water tank for microscopic visualization during treatment. Sample clots were exposed to human fresh-frozen plasma (hFFP) alone (Control); hFFP and rt-PA ([0.5 µg/ml]; “+rt-PA”); hFFP, rt-PA ([0.5 µg/ml]), and Epf ([0.63 µg/ml]; “+Epf”); and hFFP, rt-PA, Epf, and ultrasound supplied by a 2-MHz transcranial Doppler (TCD) unit (“+TCD”). Exposures were for 30 minutes at 30-37°C. Clot width was measured using a microscopic imaging technique and mean percent fractional clot loss (FCL) at 30 minutes was used to determine thrombolytic efficacy.

Results:
Each of 15 treatment groups had a minimum of 6 clots (range: 6-148) from 2 different donors (range: 2-21), for a total of 409 clots. At 37°C, FCLs for +rt-PA and +TCD groups were 44% (95% Confidence Interval: 37-52%) and 59% (54-64%) respectively (p<0.01). At 30°C, FCLs for +rt-PA and +TCD groups were 32% (27-36%) and 30% (26-33%) respectively (p not significant).

Conclusion:
Combination therapy using rt-PA, Epf, and 2-MHz US exhibits temperature dependence over a clinically applicable temperature range.
Abstract 2623: Racial Disparities in Hospital Length of Stay among Native Hawaiians and other Pacific Islanders with Ischemic Stroke
Authors: Nakagawa Kazuma , Koenig Matthew , Seto Todd , Asai Susan , Chang Cherylee
Published: July 2021

Introduction:
Native Hawaiians and other Pacific Islanders (NHPI) with ischemic stroke are younger and have more comorbidities compared to other major racial-ethnic groups. However, their impact on hospital length of stay (LOS) after ischemic stroke has not been studied.

Hypothesis:
We assessed the hypothesis that NHPI race is associated with a longer hospital LOS after ischemic stroke.

Methods:
Data from 2004 to 2010 were retrospectively obtained from the Get With the Guidelines-Stroke (GWTG-Stroke) database from The Queen’s Medical Center, the only primary stroke center for the state of Hawaii. Multivariable analyses were performed using a stepwise linear regression model to identify factors predictive of hospital LOS after ischemic stroke.

Results:
A total of 1921 patients hospitalized for ischemic stroke (NHPI 20%, Asians 53%, whites 24%, blacks 0.8%, others 2%) were studied. Univariate analyses showed that NHPI were younger (mean ages, NHPI 60±14 vs. Asians 72±14,
p
<0.0001; vs. whites 71±14,
p
<0.0001) and had higher prevalence of diabetes (NHPI 53% vs. Asians 67%,
p
<0.0001; vs. whites 22%,
p
<0.0001), hypertension (NHPI 82% vs. whites 22%,
p
<0.0001), prior stroke or TIA (NHPI 30% vs. Asians 23%,
p
=0.01), smoking (NHPI 19% vs. Asians 14%,
p
=0.01), dyslipidemia (NHPI 43% vs. whites 34%,
p
<0.01), and longer hospital LOS (NHPI 11±17 days vs. Asians 7±9 days,
p
<0.0001; whites 8±17 days,
p
<0.05). After adjusting for age, race, gender, and risk factors with predefined significance (
p
<0.1), independent predictors for hospital LOS were NHPI race (parameter estimate, 2.67; 95% CI, 1.09 - 4.22,
p
=0.001), atrial fibrillation/atrial flutter (parameter estimate, 2.22; 95% CI, 0.53 - 3.90,
p
=0.01), and age (parameter estimate, -0.04; 95% CI, -0.09 - -0.002,
p
=0.04).

Conclusions:
Native Hawaiians and other Pacific Islanders with ischemic stroke have a longer hospital length of stay compared to Asians and whites. Further studies are needed to assess if other socioeconomic factors contribute to the observed differences.
Abstract 2632: The Relationship Between MRI/PWI-Time Intensity Curve And 3-month Clinical Outcome Of The Acute Ischemic Patients Who Underwent Endovascular Reperfusion Therapy For IC Or MCA Occlusion.
Authors: NAKAZAKI MASAHITO , Mori Takahisa , Tajiri Hiroyuki , Iwata Tomonori , Miayazaki Yuichi
Published: July 2021

The purpose of our study was to investigate the relationship between MRI/PWI-Time Intensity curve (TIC) and 3-month clinical outcome following endovascular reperfusion therapy in acute ischemic stroke patients with occlusion of the internal carotid artery (ICA) or the middle cerebral artery (MCA). We retrospectively analyzed the acute stroke patients 1) who were admitted to our institution from 2004 to 2010, 2) with serious neurological symptoms, 3) who had total occlusion of the ICA or MCA displayed by MRA with DWI -PWI mismatch and 5) who underwent emergency endovascular reperfusion therapy within 8 hours from stroke onset. We investigated patient's baseline characteristics, emergency MRI findings , successful recanalization defined as TICI 2B or 3,and 3-month modified Rankin scale(3M-mRS). We evaluated PWI findings using TIC types. Region of interests were set at symmetrical positions of the bilateral MCA territories and time-intensity-curves (TICs) were calculated. The types of TICs were classified into four patterns according to the timeto peak (TP) and the reduction value of the peak signal (PV). Comparing the affected side with the contralateral side, we defined type 1 as TPa>TPc and PVaTPc and PVc/2≤PVaTPc and PVa≥PVc, and type 4 as TPa=TPc. We analyzed the relationship between the PWI/TIC and mRS at 3 months (3M-mRS) statistically. We defined favorable clinical outcome as 3M-mRS of 0-2, and assessed pre-treatment predictors for favorable clinical outcome and death within 3months by using logistic regression analysis. Seventy one patients were analyzed. Their median age was 75 years, median admission NIHSS was 17, median DWI-ASPECT score was 7, sixty three patients had cadiogenic stroke, successful recanalization was achieved in 38 patients (54.0%), and median 3M-mRS was 3. Twenty three patients (32%) had 3M-mRS of 0-2 and 11 patients (37%) died within 3 months. PWI-TICs of type 1,2,3 and 4 were in 13, 37, 21 and 0 patients, respectively. Type of PWI-TIC was significantly correlated to 3M-mRS (r=-0.24,P=0.047). The higher PWI/TIC type were, the lower 3M-mRS were. Logistic regression analysis demonstrated that independent predictors of favorable clinical outcome (3M-mRS of 0-2) were DWI ASPECTS and age, whereas, independent predictors of death within 3months from onset were type 1 of PWI-TIC (OR,5.71;95%CI,1.28-25.4, P=0.022) and admission NIHSS.

Conclusion;
In ischemic stroke patients who underwent endovascular reperfusion therapy for the ICA or MCA occlusion within 8hours from onset, type of PWI-TIC was the significant predictor for death within 3months from onset.
Abstract 2638: Potentiation of Endothelin-1-induced Ca
2+
Sensitization of Myofilament after Subarachnoid Hemorrhage
Authors: Kikkawa Yuichiro , Hirano Katsuya , Matsuo Satoshi , Nakamizo Akira , Sasaki Tomio
Published: July 2021

Introduction:
Increased vascular reactiveness in response to endothelin-1 (ET-1) plays an important role in the development of cerebral vasospasm. We elucidated some mechanisms of the increased vascular reactiveness to ET-1 using the basilar artery in a rabbit subarachnoid hemorrhage (SAH) model.

Material & Methods:
The contractile response and the expression of regulatory protein of the isolated basilar artery were evaluated.

Results:
ET-1 induced greater contraction than other agonists or 118 mM K
+
depolarization for the extent of [Ca
2+
]
i
elevation, suggesting that myofilament Ca
2+
sensitivity is a greater contributor to ET-1-induced contractions than other contractions. ET-1-induced contraction of α-toxin-permeabilized strips was significantly enhanced and sustained in SAH compared to control, suggesting that the ET-1-induced myofilament Ca
2+
sensitization was potentiated after SAH. Therefore, we investigated the intracellular signaling pathway involving Rho-associated coiled-coil protein kinase (ROCK) and protein kinase C (PKC), which are two major signaling molecules that contribute to myofilament Ca
2+
sensitization. ET-1-induced contraction of α-toxin-permeabilized control strips was blocked by inhibitors to ROCK and PKC in a concentration-dependent manner, whereas the concentration-response curve shifted to the right in SAH, suggesting that ET-1-induced myofilament Ca
2+
sensitization became less sensitive to inhibitors of ROCK and PKC after SAH. The expression of PKCα, ROCK2, PKC
-
potentiated phosphatase inhibitor of 17 kDa (CPI-17), and myosin phosphatase target subunit 1 (MYPT1) was upregulated and the level of phosphorylation of MYPT-1 at T853, and CPI-17 at T38 was increased after SAH. ET-1 induced an enhanced and sustained elevation of the phosphorylation of MYPT1 at both T696 and T853 after SAH.

Conclusion:
Ca
2+
-sensitizing effect of ET-1 on myofilaments was enhanced and prolonged after SAH. The increased expression and activity of PKCα, ROCK2, CPI-17, and MYPT1 are suggested to underlie the enhanced and prolonged Ca
2+
-sensitization. ET-1-induced potentiation of myofilament Ca
2+
sensitization may cause an increased vascular reactiveness in response to ET-1 after SAH, leading to the development of cerebral vasospasm.
Abstract 2710: Aggressive Blood Pressure Lowering in Acute Intracerebral Hemorrhage is Associated with Perihematomal Hypoperfusion and Ischemia
Authors: Aksoy Didem , Kleinman Jonathan , Snider Ryan W , Eyngorn Irina , Mlynash Michael , Straka Matus , Bammer Roland , Gean Alisa D , Fischbein Nancy , Wijman Christine A
Published: July 2021

Introduction
Optimal blood pressure control following acute ICH remains controversial. Blood pressure reduction may limit hematoma expansion, but may also cause hypoperfusion and further damage in the perihematomal region. We examined the relationship between the extent and speed of systolic blood pressure (SBP) lowering and perihematomal perfusion and ischemia.

Methods
Consecutive prospectively enrolled ICH patients with an MRI within 24 hours of symptom onset were included. Hourly SBPs were recorded from hospital presentation to MRI acquisition. Aggressive BP lowering was defined as: ≥30% reduction from baseline
and
at least one BP drop of ≥35mmHg/h. Hematoma volume was considered large if ≥30cc. FLAIR, GRE and perfusion weighted images were co-registered. T
max
maps were generated using RApid processing of PerfusIon and Diffusion (RAPID) software. The perihematomal region was defined by outlining the perihematomal edema on FLAIR images and subtracting the inner surface of blood products on the GRE generating a perihematomal rim. Statistical analyses were done using MATLAB.

Results
Twenty-seven patients were included (age: 62.7±17.9years; ICH volume: 26±26cc). Six of 27 (22%) patients experienced aggressive SBP lowering. Numbers reported: mean(IQR). The aggressiveness of SBP reduction was similar in large versus small hematomas: the percentage drop in SBP was 26% (10-33) vs. 21% (13-28), and the highest SBP drop was 43mmHg/h (29-56) versus 46mmHg/h (31-51), p=0.61 and p=0.92, respectively. Patients with SBP drops ≥35mmHg/h tended to have delayed bolus arrival (high T
max
), 6.1s (4.8-7.7) versus 5.3s (3.5-5.6) (p=0.06), as did patients with SBP drops ≥30%,T
max
values 7.3s (6.2-8.6) versus 5.3s (3.6-6.2) (p=0.014). The effect was magnified in patients with a large (≥30%)
and
fast (≥35mmHg/h) drop in SBP, despite hematoma volumes being equivalent (p=0.01,
Figure1
). Five of 6 patients with aggressive SBP lowering had a T
max
>6s. Conversely, 7 out of 8 patients with modest SBP reduction had a T
max
≤6s (
Figure2
). Out of 11 patients with T
max
>6s, 8 had DWI lesions (73%) versus 4 of 16 (25%) with T
max
≤6s (p=0.02).

Conclusions:
Aggressive SBP lowering in acute ICH is associated with high T
max
values in the perihematomal region irrespective of hematoma volume. High T
max
values in turn are associated with DWI lesions.
Abstract 2758: Comparison Of The Mortality Caused By Cerebrovascular Disease And Ischemic Heart Disease In Panama From 2001 To 2009, Its Relationship To Gender And Cardiovascular Risk Factors.
Authors: Motta Jorge A , Gordon Carlos , Gomez Beatriz , Herrera-Ballesteros Victor , Castillo Eva
Published: July 2021

Cerebrovascular disease (CVD) is among the top 5 leading causes of death in the Republic of Panama. The mortality trends of CVD and ischemic heart disease (IHD) for these diseases, its relationship to age, gender and urban vs. rural occurrence have not been studied in the last decade. We compiled data from the National Registries of Mortality from all causes spanning the years of 2001 to 2009 (n=125,519), from the National Survey of Quality of Life, Health and Living Standard (NSQLH) obtained in 25,794 individuals and data from the National Population Census of 2000 and 2009. From these data sets we calculated crude, age and gender specific and adjusted mortality rates for CVD and IHD and also calculated the crude and adjusted rates at county level. While the age adjusted death rates from CVD for 2001-2009 decreased, the same did not occur for the rates for IHD. Males had a higher mortality than females but the mortality gap between males and females was less for CVD than for IHD. Paradoxically, estimates based of the NSQLH show that the women surveyed had a higher prevalence of hypertension, obesity, and abnormal blood glucose levels. Mortality was higher in urban areas for CVD and IHD. We conclude that while there has been a reduction in the recent mortality trends for CVD mortality in Panama the same has not occurred for IHD. We have no explanation for these secular trends given the absence of a national strategy for the control of these diseases.
Abstract 2808: The Prognosis of Intravenous Thrombolysis with Alteplase Relate to Site of Cerebral Artery Occlusion
Authors: Kanzawa Takao , Mihara Ban , horikoshi Tomo
Published: July 2021

Purpose:
The objective of this study was to determine whether the arterial obstruction site is predictive of clinical outcomes in patients receiving intravenous tissue plasminogen activator (IV tPA).

Methods:
In a retrospective analysis of our stroke database between Nov. 2005 and May. 2011, we identified 91 consecutive patients who were treated with IV tPA within 3 hours after symptom onset of a stroke in the distribution of a documented ICA, proximal M1, distal M1, or M2/M3 occlusion by Magnetic resonance angiography. We analyzed the rate of favorable outcomes at 3 months (modified Rankin Scale 0 or 1) at various occlusion sites, and determined predictors of favorable outcomes.

Results:
91 consecutive patients were treated (mean age, 71 +/- 11 yr; 40.9% were women). Median baseline National Institutes of Health Stroke Scale score (NIHSS) was 10 (range, 4 to 32) and mean time form onset to IV tPA was 128+/- 33 minutes. Favorable outcomes were achieved in 55.6% and significantly correlated with age, basal NIHSS and MRI ASPECT score. Based on the occlusion site, M2/M3 occlusion had an OR of 6.4 for favorable outcomes (83.7%, 95% CI: 2.2 to 19.2, P 0.0006), whereas the odds for proximal M1 occlusion was 0.163 (25.9%, 95% CI: 0.059 to 0.447, P 0.0004), ICA occlusion was 0.378 (23.0%, 95% CI: 0.138 to 1.036, P 0.01). After adjusting for age, sex, baseline NIHSS, and MRI ASPECT score, M2/M3 occlusion occlusion were an independent predictor to achieve favorable outcomes (OR: 9.203, 95% CI: 1.896 to 45.443, P 0.006).

Conclusions:
Clinical outcome in IV tPA depends on the site of occlusion. This is important to make reasonable decisions for identifying which patients benefit in IV tPA and combined IV tPA/ interventional approach.
Abstract 2825: History of Cancer Predicts Mortality After Acute Endovascular Treatment for Ischemic Stroke
Authors: Meisel Karl , Jayaraman Mahesh , Grossberg Jonathan , Kim Anthony
Published: July 2021

Introduction:
Endovascular treatment is an emerging therapy for acute ischemic stroke. There is no clear consensus about how best to select patients that may benefit from intervention. We conducted an exploratory analysis of clinical risk factors to predict mortality after endovascular intervention in order to better understand how to improve outcomes for patients with acute ischemic stroke.

Methods:
We identified consecutive series of patients treated with endovascular therapy for acute ischemic stroke at two academic hospitals between 2005 to 2010. Key clinical data elements and clinical outcomes at the time of discharge were abstracted from medical records. We evaluated univariate and multivariable associations using logistic regression and compared mean NIH Stroke Scale between those with and without a history of cancer using the t-test.

Results:
We identified 88 patients who received endovascular intervention with intra-arterial tissue plasminogen activator (t-PA) and/or mechanical thrombectomy. The mean age of the cohort was 68.2 (SD 16.6) and 44 (55%) were female. A total of 23 (26.1%) patients died during the index hospitalization or were discharged to hospice care. A history of cancer was documented in 20 (22.7%) patients. A history of cancer was associated with a 3.2-fold (95% CI 1.1-9.1) higher odds of mortality. This association persisted after adjusting for age greater than 80 years and hypertension (OR of 4.0, 95% CI 1.3-12). The average NIH Stroke Scale was 15.6 in those with cancer compared to 14.6 without (p=0.53). A history of cancer was not associated with parenchymal hemorrhagic transformation (OR 1.2, 95% CI 0.3-4.9), IV tPA (OR 0.5, 95% CI 0.1-2.3), a TIMI score of 2b or 3 (OR 0.5, 95% CI 0.2-1.3), or an internal carotid artery occlusion (OR 1.7, 95% CI 0.5-5.1).

Conclusions:
In an exploratory analysis of consecutive patients with acute ischemic stroke treated with endovascular therapy, a history of cancer was strongly associated with significantly increased odds of mortality. One possible explanation could be that patients with cancer may have earlier withdrawal of care but the reasons for this observed association are unclear. Further investigation is necessary to verify and explain the reasons for this observation in order to improve outcomes for acute ischemic stroke patients.
Abstract 2847: The Feasibility, Efficacy And Safety Of Transbrachial Approach For Carotid Artery Stenting
Authors: Iwata Tomonori , Mori Takahisa , Tajiri Hiroyuki , Miyazaki Yuichi , Nakazaki Masahito
Published: July 2021

Backgrounds and Purpose
Transfemoral approach for carotid artery stenting (CAS) is a common technique, but patients must be bedridden for several hours following CAS. If CAS can be performed through the brachial artery route, it is less invasive for patients. The purpose of our study was to investigate the feasibility, efficacy and safety of transbrachial approach for CAS.

Materials and Methods
Transbrachial approach for CAS was started at October 2010 and data was collected prospectively. Included for analysis were patients who underwent transbrachial elective CAS from October 2010 to July 2011. Every CAS was started through the right brachial route with a 6Fr (ID) guiding sheath specifically designed for the brachial approach under local anesthesia. Technical success, periprocedural complications, 30-day major cardiovascular events (stroke, myocardial infarction and death) and 3- month stent restenosis were investigated.

Results
Forty-five patients underwent transbrachial CAS. Procedures were successful through the brachial route in every case. Periprocedural complications occurred in three cases; confusion following CAS in one case, hypotension in one case and gastrointestinal hemorrhage in one case. Three patients returned to the previous state within a few days and had no neurological deficits. No access-site related complications occurred. Patients were free on the bed immediately after CAS even during hemostasis. Neither 30- day major cardiovascular events nor 3-month stent restenosis occurred.

Conclusions
Transbrachial CAS is feasible and safe, and has the same efficacy as transfemoral CAS.
Abstract 2966: Role of the Cerebral Vascular Toll-Like Receptor Signaling Pathway in Neuroprotection Induced by Combination Therapy of VELCADE and TPA
Authors: Zhang Li , Zhang Zheng Gang , Teng Hua , Liu Xianshuang , Chopp Michael
Published: July 2021

Background and Purpose:
Toll-like receptors (TLRs) and their family members including IL-1 receptor-associated kinase-1 (IRAK1) mediate ischemic cell damage. MicroRNAs (miRNAs) including miR-146a regulate TLRs. The present study investigated whether treatment of stroke in older animals with VELCADE in combination with tPA affects expression of TLRs and miR-146a in cerebral endothelial cells.

Methods:
Wistar rats at the age of 16-18 months were subjected to right embolic middle cerebral artery occlusion (MCAo). VELCADE (0.1mg/kg) and tPA (5mg/kg) were intravenously administered 2h after MCAo (n=16). Ischemic rats treated with tPA alone (n=14) or saline (n=15) were used as control groups. Levels of TLRs and miR-146a in cerebral endothelial cells were measured. Cultured primary cerebral endothelial cells (PCECs) were used for investigating the direct effect of VELCADE on expression of miR-146a.

Results:
Quantitative RT-PCR analysis revealed that VELCADE in combination with tPA significantly increased miR-l46a levels (11±3 fold) in the cerebral endothelial cells isolated by laser capture microdissection compared with that in ischemic rats treated with tPA monotherapy (2±1). Concurrently, immunostaining showed that the combination therapy suppressed tPA monotherapy-upregulated TLR2 (44±7 vs 93±8/mm
2
in tPA), TLR4 (39±6vs 91±8), IRAK1 (16±3 vs 46±5), fibrin (17±6 vs 40±3), and NF-kB (9±2 vs 22±3) immunoreactive vessels, leading to reduction of infarct volume (14±2 vs 28±3% in tPA, and 30±3% in saline, p<0.05). These in vivo data indicate that combination therapy-upregulated miR-146a is inversely related with TLRs levels and ischemic cell damage. In vitro, Western blots showed that incubation of PCECs with fibrin at 1.5 µg/ml increased levels of IRAK1 (1.4 fold) and myeloid differentiation factor 88 (MyD88, 1.4 fold). RT-PCR analysis of PCECs showed that fibrin reduced miR-146a levels by 30 %. However, PCECs treated with VELCADE (10 ng/ml) in the presence of fibrin elevated miR-146 levels by 80% and abolished fibrin-elevated IRAK1 and MyD88 proteins. Moreover, overexpression of miR146a in PCECs downregulated IRAK1 protein, a miR-146a target, by 40%.

Conclusion:
Our data demonstrate that fibrin activates endothelial TLRs and that VELCADE-upregulated miR-146a abolishes tPA-induced TLRs, suggesting that miRNAs and the TLR signaling pathway in cerebral endothelial cells play an important role in the neuroprotective effect of the combination therapy of VELCADE and tPA for acute stroke.
Abstract 2976: Sildenafil Enhances Neurogenesis And Oligodendrogenesis In The Ischemic Brain Of Aged Mouse
Authors: Zhang Rui Lan , Chopp Michael , Roberts Cynthia , Wei Min , Wang Xinli , Liu Xianshuang , Zhang Zhenggang
Published: July 2021

Sildenafil enhances neurogenesis and oligodendrogenesis in the ischemic brain of aged mouse
Rui Lan Zhang
1
, Michael Chopp
1,2
Cynthia Roberts
1
, Min Wei
1
, Xinli Wang
1
, Xianshuang Liu
1
, Zheng Gang Zhang
1
Departments of
1
Neurology and Henry Ford Hospital, Detroit, MI, USA
2
Oakland University, Physics Department, Rochester, MI, USA.

Background and Purpose:
Nestin lineage neural progenitor cells contribute to neurogenesis in adult rodent brain under non-ischemic and ischemic conditions. The present study investigated the effect of sildenafil, a potent phosphodiesterase 5 (PDE5) inhibitor, on nestin lineage neural progenitor cells in the aged mouse after stroke.

Methods:
Male Nestin-CreER
T2
;R26R-stop-YFP mice at age 16 months were used. Tamoxifen was daily injected for 5 days to activate Cre/loxP system under control of the nestin promoter, leading to permanent YFP labeling of nestin lineage cells. These mice were subjected to permanent middle cerebral artery occlusion (MCAo) 14 days after the last tamoxifen injection. Sildenafil at 10mg/kg (n=11) or saline (n=10) was aadministered daily for 7 days starting 1 day after MCAo. All mice were sacrificed 30 days after MCAo. The number of nestin lineage cells and their fate were analyzed using immunohistochemistry staining.

Results:
Double immunofluorescent staining confirmed YFP positive cells were nestin positive. Unbiased stereological analysis revealed that sildenafil treatment significantly increased (p<0.05) the number of nestin linage cells in the ischemic subventricular zone (SVZ, 803 ± 28 vs 657 ± 41 in saline), striatum (3739 ± 162 vs 3029 ± 144 in saline), and corpus callosum (2957 ± 86 vs 2578 ± 117 in saline). Phenotype analysis showed that sildenafil substantially augmented the number of nestin lineage neuroblasts identified by doublecortin positive cells (19.4 ± 1.6 % vs 12.9 ± 1.1 % in saline), nestin lineage mature neurons measured by NeuN (6.2 ± 0.8 % vs 3.0 ± 0.6 %) and calbindin (10.8 ± 0.9 vs 7.2 ± 1.1) positive cells in the ischemic striatum. Sildenafil also significantly (p<0.05) increased the number of nestin lineage oligodendrocytes measured by 2’, 3’-cyclic nucleotide, 3’-phosphodiesterase (CNPase) positive cells in ischemic striatum (21.3 ± 1.2 vs 19.9 ± 1.4 in saline) and corpus callosum (18.9 ± 1.4 vs 14.4 ± 1.3 in saline).

Conclusion:
Our data demonstrate that sildenafil enhances neurogenesis and oligodendrogenesis in the ischemic brain of the aged mouse, which could contribute sildenafil-improved neurological outcome after stroke which we have demonstrated.
Abstract 3048: Real-World Clinical Use of CT Perfusion for Diagnosis and Prediction of Lesion Growth in Acute Ischemic Stroke
Authors: Huisa Branko N , Neil William P , Bruce Nhu T , Maya Marcel , Pereira Benedict , Lyden Patrick D D
Published: July 2021

Background:
Diffusion-weighted imaging (DWI) detects acute ischemia with a high sensitivity. In research centers, qualitative CT perfusion (CTP) mapping correlates well with DWI and may accurately differentiate the infarct core from ischemic penumbra. The value of the CTP in real-world clinical practice, however, has not been fully established. We investigated the yield of CTP - derived cerebral blood volume (CBV) and mean transient time (MTT) for the detection of cerebral ischemia in a sample of acute ischemic stroke (AIS) patients.

Methods:
In a large metropolitan academic medical center that is a certified Primary Stroke Center (PSC) we retrospectively studied 162 patients who presented between January 2008 and July 2010 with symptoms suggestive of AIS. All patients had an initial Code Brain protocol including non-contrast head CT, CTP, and CTA. As clinically indicated, some patients underwent follow up brain MRI within 48 hours. Acute perfusion maps were derived in real time by a trained operator. From the obtained images CBV, MTT and DWI lesion volumes were manually traced using planimetry (ImageJ v1.42) by two stroke neurologists blinded to clinical information. Volumes were calculated using the Cavaleri theorem. Sensitivity, specificity and statistical analysis were calculated using Graph Pad 5.0.

Results:
Of 162 patients with acute stroke-like symptoms, 73 had DWI lesions. The sensitivity and specificity to detect abnormal DWI signals were 23% and 100%, for CBV; and 43.8% and 98.9% for MTT. For DWI lesions ≥5ml the yield was 59.3% for CVB and 77.8% for MTT. For lesions ≥10ml the yield was 68.4% for CBV and 89.5% for MTT. In patients with NIHSS ≥5, CBV predicted abnormal DWI in 22.6% and MTT in 35.5%. In patients with NIHSS ≥10, CBV and MTT, both had a yield of 50.0%. A CBV - MTT mismatch of >25% predicted MRI lesion extension in 81.25% of the cases. There were small but significant correlations for DWI versus CBV lesion volumes (

r
2

0.32,
P=
0.0001), and for DWI versus MTT lesion volumes (
r
2
0.29,
P
<0.0001). Correlation between DWI and perfusion maps for MCA territory infarcts were CBV (

r
2

0.3,
P
<0.0001) and MTT (

r
2

0.45,
P
<0.0001).

Conclusions:
In real-world deployment during a Code Brain protocol in a busy PSC, acute imaging with CTP did not predict DWI lesions on brain MRI with sufficient accuracy. In patients with large lesions the predictive value was better.
Abstract 3051: Blood Pressure Thresholds to Predict the Cause of Intracerebral Hemorrhage
Authors: Komshian Sevan R , Kleinman Jonathan T , Snider Ryan W , Eyngorn Irina , Aksoy Didem , Finley-Caulfield Anna , Venkatasubramanian Chitra , Wijman Christine A
Published: July 2021

Introduction:
Chronic hypertension is a common cause of spontaneous intracerebral hemorrhage (ICH), but not all patients who are hypertensive on hospital presentation have an ICH caused by hypertension (htnICH). We sought to determine blood pressure (BP) thresholds that correlated with a presumed htnICH in a prospective cohort.

Methods:
The NIH-funded Diagnostic Utility of MRI in Spontaneous Intracerebral Hemorrhage (DASH) study prospectively enrolled consecutive ICH patients to determine the utility of routine MRI in the diagnosis and management of these patients. Contrast angiography was pursued in a predefined patient subset. At 3 months, ICH cause was determined by the treating stroke physician after review of all clinical information, including MRI in the acute and chronic phase, pathology, and clinic follow-up, as available. Statistical analyses were done using SPSS: χ2; 2 tailed t-tests; and Mann-Whitney U tests were used as appropriate. Receiver operator characteristic (ROC) curves were created and results expressed as area under curve (AUC).

Results:
We included 136 patients in this report (age: 63±17yrs; ICH volume: 22±27cc; NIHSS: 9±8; GCS: 13±3). Of these, 70% had a history of hypertension, 40% had an admission SBP> 180mmHg, and 22% an admission SBP >200mmHg. Sixty patients (44%) had htnICH as their final diagnosis. A history of hypertension was associated with htnICH (χ2=11.8, p<0.001), but 48% (46/95) of patients with a history of hypertension did not have a htnICH. Patients with a htnICH had: higher SBP (189 vs 157mmHg, p<0.0001); higher MAP (131 vs 110mmHg, p<0.0001), higher NIHSS (12 vs 6.5, p<0.0001); smaller ICH volumes (16.6 vs 26.0cc, p=0.03); and non-lobar hematomas (χ2=62.3, p180mmHg was 74% specific and 58% sensitive for a subsequent diagnosis of htnICH, a SBP> 200mmHg was 90% specific and 37% sensitive, and a MAP >132mmHg was 90% specific and 45% sensitive. Using ROC analysis, MAP predicted hypertensive etiology with an AUC of 0.75 (p<0.0001, 95% CI: 0.67-0.83). Patients with htnICH and MAP 132mmHg based on age, NIHSS, gender, ICH volume, or ICH location (lobar vs non-lobar). Conversely, patients with non-htnICH and MAP >132mmHg on admission tended to have larger ICH volumes (44 vs 24cc, p=0.07) and higher NIHSS (10 vs 6, p=0.21), but did not differ by location from those with a MAP<132mmHg. Non-lobar location alone was 74% specific and 93% sensitive for htnICH, and a non-lobar ICH or a MAP>132mmHg was 64% specific and 95% sensitive for htnICH.

Conclusions:
In our cohort, a history of hypertension predicted htnICH no better than chance. An admission SBP >200mmHg or a MAP >132mmHg predicted htnICH in 90% of these patients, but missed two-thirds of cases. ICH location alone was a sensitive predictor of htnICH, but blood pressure thresholds were more specific.
Abstract 3060: Racial Disparities in Early Institution of “Do Not Resuscitate” Orders Influence Survival in Acute Ischemic Strokes.
Authors: Bhattacharya Pratik , Tiwari Ambooj , Watson Sam , Millis Scott , Chaturvedi Seemant , Rajamani Kumar
Published: July 2021

Background:
The importance of early institution of “Do Not Resuscitate” (DNR) orders in determining outcomes from intracerebral hemorrhage is established. In the setting of acute ischemic stroke, African Americans tend to utilize critical care interventions more and palliative care options less than Caucasians. Recent epidemiological studies in acute ischemic stroke have shown a somewhat better survival for African Americans compared with Caucasians. Our hypothesis was that racial differences in early institution of DNR orders would influence mortality in acute ischemic stroke.

Methods:
a retrospective chart review was conducted on consecutive admissions for acute ischemic stroke across 10 hospitals in Michigan for the year 2006. Subjects with self reported race as African American or Caucasian were selected. Demographics, stroke risk factors, pre morbid status, DNR by day 2 of admission, stroke outcome and discharge destination were abstracted.

Results:
The study included 574 subjects (144 African American, 25.1%; 430 Caucasian, 74.9%). In-hospital mortality was significantly higher among Caucasians (8.6% vs. 1.4% amongst African Americans, p=0.003). More Caucasians had institution of DNR by day 2 than African Americans (22.5% vs. 4.3%, p<0.0001). When adjusted for racial differences in DNR by day 2 status, Caucasian race no longer predicted mortality. Caucasians were significantly older than African Americans (median age 76 vs. 63.5 years, p<0.0001); and age was a significant predictor of DNR by day 2 and mortality. In the adjusted analysis, however, age marginally influenced the racial disparity in mortality (
table
). Caucasians with coronary disease, atrial fibrillation, severe strokes and unable to walk prior to the stroke tend to be made DNR by day 2 more frequently. Only 27.1% of Caucasians with early DNR orders died in the hospital, whereas 20.8% were eventually discharged home.

Conclusions:
Early DNR orders result in a racial disparity in mortality from acute ischemic stroke. A substantial proportion of patients with early DNR orders eventually go home. Postponing the use of DNR orders may allow aggressive critical care interventions that may potentially mitigate the racial differences in mortality.
Abstract 3099: Detection Of Intracerebral Hemorrhage In An In Vivo Porcine Model Using Radiofrequency Electromagnetic Radiation
Authors: Korfhagen Joseph J , Kandadai Madhu , Beiler Shauna , Wagner Kenneth R , Clark Joseph F , Flaherty Matthew L , Adeoye Opeolu , Shaw George J
Published: July 2021

There is a need for continuous, non-invasive neurologic monitoring in patients who are suffering from a significant neurologic insult such as stroke, intracerebral hemorrhage (ICH) or traumatic brain injury. Currently, these patients are typically sedated and/or intubated in the ICU setting, making it difficult for the clinician to assess their neurologic status. A device capable of non-invasively determining acute changes in brain function would be of great utility in this clinical setting. Here, we present the results of a pilot study of a non-invasive radiofrequency (RF) electromagnetic (EM) radiation device to detect acute blood in a well-established in vivo porcine ICH model.

Methods:
Two antennae were placed collinearly with the upper eyelids of a sedated, anesthetized pig, after local IACUC approval of the protocol. An RF signal was transmitted by one antenna across the head of the pig and received by the other antenna, which was connected to a spectrum analyzer to measure received power (Pr). Blood (3 mL) was infused into the frontal lobe white matter at the level of the upper eyelids. Pr values were collected for the healthy pig (Pr(control)), after infusion of ICH (Pr(ICH)), and 30 minutes after Pr(ICH) measurement (Pr(clot)). Clot size was determined by measuring the clot in post-mortem frozen brain slices. Seven pig experiments were conducted. A student’s paired t-test was used for statistical analysis, and P < 0.05 was considered to be significant.

Results:
A 12% (SD: 6%) increase in Pr(ICH) was seen compared to Pr(control) (P = 0.003). Pr(clot) also increased by 13% (SD: 10%) compared to Pr(control) but the difference was not significant (P = 0.053). The average clot size was 1.2mL.

Conclusion:
It has been demonstrated that an RF EM signal can be used to detect acute ICH in an in vivo porcine model. A non-invasive sensor based on this technique may be useful in monitoring the neurologically injured patient.
Abstract 3115: Low-Level Laser Therapy Protects Against OGD-induced Neurotoxicity Of Primary Cultured Mouse Cortical Neurons
Authors: Yu Zhanyang , Liu Ning , Lo Eng H , McCarthy Thomas J , Wang Xiaoying
Published: July 2021

Background:
Low level light (or laser) therapy (LLLT) has been studied and practiced for promoting wound healing, reducing pain, inflammation, and ischemic tissue damage. Recently, a series of experimental and clinical investigations have suggested that LLLT may be a novel therapy against hypoxic/ischemic brain damage. A clinical trial of LLLT therapy for ischemic stroke is now on going. However, the molecular mechanism of LLLT-conferred neuroprotection remains poorly defined. In this study, we tested our hypothesis that LLLT may attenuate impairments of mitochondrial function induced by hypoxic/ischemic insults in primary cultured mouse cortical neurons.

Method:
At day 9 of culture, primary neurons were subjected to 4 hr OGD followed by reoxygenation. One 810-nm LLLT treatment was applied for 2 minutes at 2 hr after reoxygenation. Neurotoxicity was measured after 20 hr after reoxygenation by LDH release assay. We also measured MTT reduction and mitochondria membrane potential (MMP) at 2 hr after LLLT treatment as markers of mitochondrial function.

Results:
The neurotoxicity study showed that 4 hr OGD plus 20 hr reoxygenation caused 33.8± 3.4% neuronal cell death, while LLLT treatment significantly reduced the neuronal death rate to 23.6± 2.9% (30.2% reduction, n=6, p smaller than 0.05). Mitochondrial functional assays showed OGD decreased MTT reduction to 75.9± 2.68%, but LLLT treatment significantly rescued MTT reduction to 87.6±4.55% (15.4% improvement, n=6, p smaller than 0.05). Furthermore, after OGD, MMP was reduced to 48.9±4.39%, while LLLT treatment significantly ameliorated this reduction to 89.6± 13.9% (83% improvement, n=4, p smaller than 0.05) compared to normoxic controls.

Conclusion:
The present study suggests that LLLT treatment is protective against OGD-induced neurotoxicity of primary neurons and that this protection may be conferred through preservation or rescue of mitochondrial function.
Abstract 3133: Impact of Post-stroke Isolation on Stroke Outcome
Authors: Venna Venugopal R , Xu Yan , Li Jun , Liu Fudong , McCullough Louise D
Published: July 2021

Background:
Psychosocial factors are increasingly accepted as critical factors in post-stroke recovery, mortality and morbidity. Although, emerging data from clinical and population based studies support the role of social support in improved functional recovery and reducing the risk of mortality, to date no experimental studies have investigated such effects in post-stroke animal models. The aim of this study is to investigate for the impact of post stroke housing and the effects of long-term social isolation and pair housing with either a healthy or a stroked partner, and explored for the mechanisms.

Methods:
Male mice (20-25g; C57BL/6N, Charles River Labs), all initially pair housed, were subjected to right middle cerebral artery occlusion (MCAO - 60min) and then randomly assigned to a specific housing condition - isolated, paired with a stroke partner or paired with a healthy partner. Infarct size was quantified with TTC 72h after stroke (n=8/grp). We then investigated the effects of housing on long-term functional recovery using corner test, cylinder test, forced swim test (FST) and tail suspension test (TST). We further explored the mechanisms underlying the improved behavioral recovery by injecting BrDU 150mg/kg/day i.p. for 5 days starting from day 3 post-stroke (n=8/grp), and assessing changes in BDNF levels by western-blot analysis (n=4/grp). Data were expressed as mean±sem. Two-way ANOVA was performed and P value < .05 was set for statistical significance.

Results:
Post-stroke housing conditions can significantly impact infarct size; we observed that mice isolated after stroke had increased infarct volume compared to pair housed mice in all three brain regions (Cortex: 63.2±2.5 vs 40.0±6.2; p<0.01); (Striatum: 86.6±2.2 vs 67.7±2.9; p<0.01); (Total: 60.9±1.3 vs 32.6±4.3; p<0.01). Although post-stroke housing with healthy vs a stroked partner did not influenced infarct size (p>0.05), animals pair housed with healthy partner showed a significantly improved functional recovery by as early as day 15 in the cylinder and corner tests (p<0.05). Increased mobility was observed in FST and TST in PH mice compared to SI mice at day 90 (p<0.05). Consistently, housing with a healthy partner increased BrDU positive cells (p<0.05) and enhanced BDNF expression compared to other cohorts (SI 1±0.1; PH with stroke partner 1.9±0.2; PH with healthy partner 2.6±0.1; n=4/grp), no changes were seen in sham mice.

Conclusions:
Post-stroke housing has an important impact on stroke outcome; isolation has a detrimental effect on infarct size compared to pair housed cohorts. Interestingly, independent of infarct size, housing with a healthy partner hastened recovery compared to those stroke mice housed with partner that had also been subjected to stroke. Molecular analysis indicates the involvement of BDNF and neurogenesis may be important regulators of post-stroke housing induced functional recovery.