bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 168: Coated-Platelets Improve TIA/Stroke Prediction in Asymptomatic Internal Carotid Artery Stenosis
Authors: Kirkpatrick Angelia , Vincent Andrea , Dale George , Prodan Calin
Published: March 2022

Background:
Coated-platelets, a subset of procoagulant platelets observed upon dual agonist stimulation with collagen and thrombin, support a robust prothrombinase activity and provide a unique measure of platelet thrombotic potential. Coated-platelet levels are increased in large artery stroke compared to controls, and higher levels are associated with early stroke recurrence. We now examine whether coated-platelet levels predict TIA/stroke in asymptomatic internal carotid artery (ICA) stenosis.

Methods:
Consecutive patients referred for carotid Doppler evaluation were enrolled. Those taking anticoagulants, with dementia, or TIA/stroke within 6 months before enrollment were excluded. Coated-platelets were determined at baseline and reported as percent of cells converted to coated-platelets. Subjects were followed for up to 3 years for TIA/stroke. A receiver operating characteristic curve (ROC) analysis was conducted to compare performance of two models in predicting incident TIA/stroke. The first model included stenosis severity (<70% or ≥70%) while the second model included stenosis severity (<50% or ≥50%) and coated-platelet level as predictors.

Results:
We enrolled 343 patients. Follow-up ranged from 4 days to 39.7 months (mean 10.6 months). Fourteen TIA/strokes were observed. Ten were carotid-related. ROC analysis showed significant improvement in the predictive ability of the stenosis (≥50%) plus coated-platelets model compared to the stenosis (≥70%) only model (AUC: 0.88 ± 0.05 versus 0.71 ± 0.08, respectively; p=0.05). A cut-off of 46.5% for coated-platelet levels in combination with stenosis ≥50% yielded a sensitivity of 0.70 (0.42-0.98; 95% CI), specificity of 0.91 (0.88-0.94), positive predictive value of 0.18 (0.06-0.31), and a negative predictive value of 0.99 (0.98-1.0). Coated-platelet levels at 6 months did not significantly differ from baseline (p=0.69).

Conclusions:
Coated-platelet levels identify asymptomatic ICA stenosis patients at low risk for carotid-related stroke, which suggests a role for coated-platelets in risk stratification prior to revascularization.
Abstract 169: Diet-induced Diabetes Impairs Neovascularization and Functional Recovery After Ischemic Stroke
Authors: Qu Zhi , Li Weiguo , Prakash Roshini , Fagan Susan C , Ergul Adviye
Published: March 2022

Introduction:
Acute ischemic stroke is the leading cause of long-term disability in the United States. While it is known that diabetes worsens stroke outcome and diet-induced metabolic disease is on the rise, the impact of diabetes and especially diet-induced metabolic disease, on repair and recovery after stroke is unclear. Accordingly, the goal of this study is to test the hypothesis that diet-induced diabetes impedes vascular restoration and functional recovery after ischemic stroke.

Methods:
Diabetes was induced by a combination of high fat (45%) diet and low dose (30mg/kg) streptozotocin (STZ) in male Wistar rats. Rats fed by control diet were used as control group. Eight weeks after the induction of diabetes, control or diabetic rats were subjected to 90-minute temporary middle cerebral artery occlusion and neurobehavioral outcome was assessed at Days 1, 3, 10 and 14. After fluorescein isothiocyanate-dextran (FITC) injection, the cerebral angioarchitecture was assessed by 3-dimensional reconstruction of the vasculature using z-stacks images obtained by the confocal microscopy. Vascular volume, surface area, and branch density were assessed as indices of neovascularization.

Results:
The average blood glucose was 230 and 84 mg/dL in diabetic and control groups, respectively. All indices of neovascularization (ipsilateral cortex and striatum) were lower and neurological deficit (composite score) was worse in diabetic animals (Table, n=3, *p<0.05).

Conclusions:
These results suggest that diet-induced diabetes impairs neovascularization and functional outcome after ischemic stroke. Further understanding of the underlying mechanisms will identify new targets towards developing therapeutic strageties for stroke recovery in diabetes.
Abstract 178: Desmopressin Increases Platelet Activity After Acute Intracerebral Hemorrhage
Authors: Naidech Andrew M , Liotta Eric M , Guth James , Bendok Bernard R , Rosenow Joshua , Prabhakaran Shyam , Bernstein Richard A , Maas Matthew B , Kwaan Hau C
Published: March 2022

Background:
Acute treatment for intracerebral hemorrhage (ICH) frequently centers on minimizing hematoma volume growth. Aspirin use or reduced platelet activity is a risk factor for hematoma growth and worse functional outcomes at 3 months. Many clinicians use platelet transfusion, although there are few data to support that practice. We tested the hypothesis that desmopressin, which reduces bleeding in the setting of aspirin use by increasing von Willebrand factor (wVF), would improve platelet activity in patients with ICH.

Methods:
We prospectively screened patients with acute ICH for aspirin use or reduced platelet activity. The patient or a proxy was asked for consent for the administration of desmopressin 0.4 mcg/kg IV. The primary outcome was change in platelet activity, measured by the platelet function analyzer (PFA, Siemens AG, Germany), and vWF antigen, before and one hour after treatment. Parameters before and after treatment were compared with a paired t-test. We also prospectively documented acute adverse events. The FDA issued an exemption in response to a request for an IND. The study is registered at clinicaltrials.gov as NCT00961532.

Results:
Twelve patients have been enrolled, of whom six were men, seven (58%) were Caucasian, and three (25%) were Hispanic. The PFA closure time decreased from 172 sec. (abnormal) to 134 seconds (normal), while vWF antigen increased from 214 to 256 percent of expected activity (both P<0.05). Desmopressin was well tolerated, with one patient each experiencing a new fever or hypotension.

Conclusions:
In this pilot study, desmopressin seems to be relatively safe and well tolerated in patients with ICH, and increases platelet activity
in vitro
. Desmopressin may be a reasonable substitute for, or addition to, platelet transfusion to transiently increase platelet activity in patients with acute ICH.
Abstract 183: Examining the Effect of Intra-Arterial Therapy on Outcomes in IV tPA Ineligible Ischemic Stroke Patients
Authors: Sarraj Amrou , Boehme Amelia K , Sun Chung-Huan J , Bibars Wafi , Olowu Adeola , Sitton Clark W , Supsupin Emilio P , Martin-Schild Sheryl , Gupta Rishi , Grotta James C , Savitz Sean I
Published: March 2022

Background:
Recent randomized trials (RCTs) have failed to show benefit of intra-arterial therapy (IAT) compared with patients given IV tPA alone. Many patients, however, are ineligible for IV tPA, who were not included in IMS-3, MR-RESCUE or SYNTHESIS. We investigated potential treatment effects of IAT in patients with acute ischemic stroke ineligible for tPA.

Methods:
In a US multicenter retrospective cohort study, we identified 476 AIS IV tPA ineligible patients with large artery occlusions (LAO) from 01/08 to 06/13. Inclusion criteria was <6hrs from symptom onset for anterior circulation and <12hrs for posterior circulation. Patients were divided into two arms (IAT vs No IAT). Logistic regression with good and bad (discharge mRS 0-2 and 4-6 respectively) outcome was performed to compare the two arms. Univariate and multivariate analyses evaluated independent predictors of good outcome after IAT.

Results:
Table 1 shows baseline characteristics. Presentation >4.5 hrs (52%), high INR (11%) and recent procedure (10%) were the main reasons for IV tPA ineligibility. IAT patients had 4 times greater odds of good (OR 3.9, 95%CI 1.5-10, p=0.004) and significantly less odds of poor outcome (OR 0.3, 95%CI 0.17-0.55, p<0.0001) compared to those without IAT. Significance was maintained under nearly all conditions after adjustment was made for covariates (Table 2). The distribution of mRS scores demonstrated a shift towards better outcomes in IAT treated patients (Fig 1) in spite of higher death rates in this group. In univariate analysis, good ASPECTS (8-10), good reperfusion (TICI ≥2b) and time were independent predictors of good outcome after IAT. Start of IAT in the first 3hrs from onset was associated with 5 times the odds of a good outcome than later IAT initiation (5.3, 95%CI 1.99-14.6, p=0.001).

Conclusion:
IAT may improve clinical outcomes in patients with LAO who are IV tPA ineligible. Testing for IAT efficacy in this patient population will require RCTs to validate our findings.
Abstract 186: Effectiveness of Endovascular Recanalization for Acute Stroke: A Transition Toward Superiority Over Intravenous Thrombolysis
Authors: Kim Beom Joon , Han Moon-Ku , Park Tai Hwan , Park Sang-Soon , Lee Kyung Bok , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi Sun , Cha Jae Kwan , Kim Dae-Hyun , Lee Jun , Lee Soo Joo , Ko Young-Chai , Park Jong-Moo , Kang Kyusik , Cho Yong-Jin , Hong Keun-Sik , Kim Joon-Tae , Choi Jay Chol , Kim Dong-Eog , Lee Juneyoung , Lee Ji Sung , Gorelick Philip B , Yoon Byung-Woo , Bae Hee-Joon
Published: March 2022

Background:
There is skepticism in clinical practice about the comparative effectiveness of endovascular recanalization compared to intravenous thrombolysis for acute ischemic stroke, and there is a paucity of information about effectiveness and safety trends.

Methods:
We identified 872 acute ischemic stroke patients who underwent recanalization therapy with intravenous thrombolysis only (IVT; n=533) or endovascular recanalization with or without intravenous thrombolysis (EVT; n=339) from a prospective, multicenter stroke registry database between April 2008 and January 2012. All study subjects had NIHSS score ≥10 and arrived within 4.5 hours of onset. Inverse probability of EVT weighting by propensity score was used to remove baseline imbalance between treatment groups. Primary outcome was mRS score 0 – 2 at the time of discharge. Year-by-year effectiveness and safety of EVT over IVT were estimated with further adjustment by age, NIHSS score, onset to arrival time, duration of hospitalization and treatment year.

Results:
Before 2010, the primary outcome was not associated with treatment modality. However in 2011, EVT increased the odds of better primary outcome compared to IVT (adjusted OR, 1.87; 95% CI, 1.08 – 3.23). Also in year 2011, EVT became superior to IVT for mRS score 0 – 2 (1.99; 1.10 – 3.59) at 3 months after stroke. The odds of mortality during admission and at 3 month and symptomatic hemorrhagic transformation were not different between recanalization methods throughout the study period (see Figure). Subgroup analyses showed that effect estimates from EVT were significantly modified by total stroke volume of hospital (higher in ≥30 stroke cases per month) and time from onset to arrival (higher in ≥2-hour delay).

Conclusion:
Over time, endovascular recanalization has become superior to intravenous thrombolysis for improvement of clinical outcomes in acute ischemic stroke.
Abstract 191: Optical Inhibition of Striatum Neuron Promotes Recovery After Ischemic Stroke
Authors: He Xiao s , Miao Peng , Lv Yi f , Lin Xiao j , Tang Yao h , Tang Guang h , Zhang Zhi j , Wang Yong t , Yang Guo Y
Published: March 2022

Introduction:
Neurons of peri-infarct region in the cortex have effects on neurogenesis and remodeling after ischemic stroke. However the role of penumbral striatum neuron in neurogenesis and remodeling after ischemic stroke is unknown. In this study, we use optogenetic tools to specifically regulate the activity of striatum neuron and investigate its roles in neurogenesis and remodeling after ischemic stroke.

Methods:
Lentivirus carrying NpHR and YFP fusion protein under CaMKII promoter was injected into striatum of experimental mice. 7 days after injection, ferrule with fiber or optrode was implanted at the same position and MCAO surgery was performed 14 days after the injection. 4 days after MCAO, mice were stimulated with constant 594 nm laser for two 15-min sessions each day for 4 days. Electrophysiology test was used to confirm the validity of NpHR in vivo. Neurobehavioral tests were carried out at 3, 7 and 35 days after MCAO.

Results:
When stimulated with 594nm laser, the firing rate of striatum neuron was reduced in NpHR transduced mouse after MCAO. Immunohistochemistry showed that the number of BrdU and DCX double positive cells was significantly increased in the SVZ area. Nestin positive cells were increased both in SVZ and peri-infarct area. Western blotting showed that Netrin-1 expression was significantly up-regulated. BrdU and NeuN double positive cells was increased and brain atrophy volume was reduced in laser-stimulated mice compared with control mice (p<0.05). Neurobehavioral test showed that inhibition of striatum neuron promotes motor function after MCAO compared to the control (p<0.05).

Conclusion:
Laser induced activation of NpHR reduces the firing rate of penumbral striatum neuron using optogenetics tools. Inhibition of striatum neuron promotes proliferation and migration of neural progenietor cells and neurobehavioral function recovery. This effect is related to Netrin-1 secretion.
Abstract 193: Imaging Biomarkers to Predict Fluency and Naming in Chronic Nonfluent Aphasic Patients
Authors: Wang Jasmine , Marchina Sarah , Norton Andrea , Schlaug Gottfried
Published: March 2022

We previously showed that a combined variable of lesion site and size, the Arcuate Fasciculus lesion load (AF-LL), predicted speech fluency in chronic aphasic patients. In the current study, we compare the correlations between speech fluency and naming measures with two lesion markers in a large group of patients: the previously established structural lesion marker (i.e., AF-LL) and a new functional lesion marker (i.e., the functional grey matter lesion load (fGM-LL)). fGM-LL was constructed from functional brain imaging of overt speaking tasks in a group of twelve healthy elderly control participants. High-resolution structural brain images were acquired to reconstruct the arcuate fasciculus (AF) as a structural map. In addition to these two canonical maps, a combined AF-fGM was derived from summing fGM and AF maps. Each canonical map was overlaid with lesion masks of 50 chronic aphasic patients with varying degrees of impairment in speech production to calculate a functional and structural lesion load value for each patient. Lesion loads were then regressed with measures of speech fluency and naming. We found that both AF-LL and fGM-LL independently predicted speech fluency and naming ability (p<0.01); however, AF lesion load explained most of the variance for both measures. The combined AF-fGM lesion load did not have a higher predictability than either AF-LL or fGM-LL alone. Clustering and classification methods confirmed AF lesion load was best at stratifying patients into severe and non-severe outcome groups of speech fluency with 96% accuracy and naming with 86% accuracy. Our classification model showed that an AF-LL of greater than 4cc was the critical threshold that determined poor fluency and naming outcomes. Thus, surrogate biomarkers of language impairments may help healthcare providers make more accurate predictions of outcome and help to stratify patients for experimental studies.
Abstract 194: BDNF Knockdown Abrogates AT1 Blockade -Induced Improvement in Stroke Outcome
Authors: Alhusban Ahmed , Fouda Abdelrahamn , Pillai Bindu , Ergul Adviye , Fagan Susan C
Published: March 2022

Background:
Brain derived neurotrophic factor has been shown to play an important role in long term functional recovery after stroke. Unfortunately, the clinical exploitation of this protein is limited due to the lack of pharmacological interventions that regulate its expression. Angiotensin II receptor blockers (ARBs) increase BDNF expression in both normotensive and hypertensive animals. We investigated the possible interaction between acute ARB treatment and BDNF in terms of long term functional recovery after stroke.

Methods:
Male normotensive wistar rats received bilateral ICV injections with lentiviruses expressing either BDNF shRNA or vector. 14 days after injection, animals were subjected to 90 minutes MCAO and randomized to either candesartan 1mg/kg or saline at the time of reperfusion. Functional recovery was assessed 24 hours after stroke and every 72 hours for 14 days using a blinded battery of validated behavioral tests. Animals were then sacrificed and their brains processed for immunohistochemistry.

Results:
Bilateral injection with shRNA reduced the expression of BDNF by more than 70% (p=0.0045). Acute ARB administration ameliorated stroke induced functional deficits throughout the follow-up period after stroke in all used tests and Day 14 data is shown on the Table. This pro-recovery effect was totally ablated in BDNF knocked down animals. Acute ARB therapy also increased the number of new brain blood vessels (CD31/Ki67 positive cells) which was also BDNF dependent.

Conclusion:
1.

Acute ARB- induced functional recovery after stroke is BDNF dependent.

2.

This pro-recovery effect is associated with a BDNF dependent proangiogenic state.

Table 1: Experimental data summary. SD are shown in parenthesis. a,b,c. Pairs of means with different letters are significantly different from each other
Abstract 205: Association of Statin Use With the Risk of Subarachnoid Hemorrhage in Medicare Patients With Unruptured Cerebral Aneurysms
Authors: Bekelis Kimon , Smith Jeremy , Zhou Weiping , Roberts David , Skinner Jonathan , Morden Nancy
Published: March 2022

Background:
Animal studies have demonstrated that statins decrease cerebral aneurysm progression and the risk of subarachnoid hemorrhage (SAH). A protective effect has also been observed in human studies of abdominal aortic aneurysms. We investigated the association between statin use and SAH in Medicare beneficiaries.

Methods:
We used the 40% random sample Medicare denominator file and corresponding inpatient, outpatient (2003-2011) and prescription (2006-2011) claims to conduct a retrospective cohort study of patients diagnosed with unruptured cerebral aneurysms, between 2003 and 2011. We used propensity-adjusted logistic models to investigate the association of statin use with the risk of SAH, out-of-hospital death, and undergoing intervention more than 3 months after the diagnosis (as a marker of disease progression), as well as the composite outcome of all events.

Results:
We identified 27,574 patients with unruptured cerebral aneurysms (average age 72.3 years, 72.7% female); mean follow up was 29.8 months. Statins were used by 41.4%. Overall, 1,497 patients developed SAH and 725 underwent intervention (coiling or clipping) before aneurysm rupture. Current or recent statin use was not associated with decreased risk of SAH (OR 1.05, 95% CI 0.93 to 1.17), even after stratification on tobacco use/chronic pulmonary disease. Similarly, no association was observed between statin use and the likelihood for operative intervention (OR 0.89, 95% CI 0.75 to 1.10). The risk of the composite outcome was lower among ongoing statin users, compared to remote or no users (OR 0.72, 95% CI 0.68 to 0.77).

Conclusions:
Use of statins by patients with unruptured cerebral aneurysms was not associated with decreased risk of SAH. This underscores the differences in human physiology from the animal models used. The lack of the protective effect of statins seen in aortic aneurysms may be explained by the non-atherosclerotic nature of cerebral aneurysms.

Funding:
National Institute on Aging (PO1- AG19783).
Abstract 206: Intraarterial (IA) Therapy of Cerebral Vasospasm: Comparison of Single Agent vs Multiple Agent Infusion
Authors: Chen Peng Roc , Erkmen Kadir , Sanzgiri Aditya , Pise Mayurika , Aisiku Imo
Published: March 2022

Background:
Cerebral vasospasm remains a major cause of morbidity and mortality in patients with subarachnoid hemorrhage. Vasospasm treatment typically includes IA infusion of vasodilators; however the optimal agent/s have not been elucidated. National surveys suggest that IA treatment algorithms vary between centers and commonly involve use of a single agent. We hypothesize that IA infusion of a cocktail of multiple vasodilators is more efficacious than single agent treatment.

Methods:
A prospective case series of consecutive patients with cerebral vasospasm (Group 2, N=50 patients, 106 vessels) treated between 2010-13 with IA infusion of a specific cocktail of multiple agents (nitroglycerin, verapamil and nicardipine) at a tertiary center, were compared to a historic control group (Group 1, N=54 patients, 116 vessels) at the same center between 2008-10 treated with a single agent (nicardipine or verapamil). Patient demographics, age, and modified Rankin score (mRS) at discharge and 3 months were collected in the cerebrovascular database. Arterial luminal diameters were measured on cerebral angiograms both pre-infusion (PrID) and post-infusion (PoID). The Improvement Ratio (IR) = (PoID - PrID/PrID) x 100 was calculated and statistically compared between groups using the T test.

Results:
Group 2 demonstrated statistically significant improvement IR 45.8% (SD 36.6) than Group 1 IR 10.9% (SD 12.0), P<0.001. Multiple agent infusion resulted in an average of 34.9% greater vessel diameter improvement than single agent therapy. Comparison of IR between different single agents within group 1 (nicardipine and verapamil) demonstrated no difference in vessel diameter change. Age of the patient had no effect on efficacy in either group. Patient outcomes measured by mRS were similar at discharge and at 3 months follow-up.

Discussion:
Treatment of cerebral vasospasm with an IA cocktail of nitroglycerine, verapamil, and nicardipine provides significantly better angiographic improvement of vasospasm than single agent therapy. This effect appears independent of patient age. Outcomes measured by mRS at discharge and 3 months were not significantly different, however will be examined in an ongoing prospective multi-center trial.
Abstract 213: Stroke Severity Adjusted EMS Triage Has Benefits for Bypassed Primary Stroke Centers
Authors: Allen Evan , Husty Todd , Claunch Joshua D , Banerjee Paul , Lovec Rhonda , Richards Donald , Qureshi Adnan I
Published: March 2022

Background:
Stroke Severity Adjusted EMS triage (SSAET) has been recommended to bypass Primary Stroke Centers (PSC) and transport acute severe strokes to Comprehensive Stroke Centers (CSC) for Neurosurgery, endovascular intervention and research to develop new treatments. There is increased emphasis on hospitals' stroke major complication and mortality rates. Some Hospitalists are reluctant to admit Intracerebral hemorrhage (ICH) patients without in house Neurosurgery coverage. Outcome differences of directly admitted PSC and bypassed CSC patients have not yet been described.

Methods:
Florida Hospital Stroke Program requests Seminole County EMS use SSAETbypass of Florida Hospital Altamonte PSC to transport acute severe stroke 9.1 miles away to Florida Hospital Orlando CSC. We retrospectively analyzed 310 suspected acute severe strokes/Transient Ischemic attacks(TIA) EMS bypassed to the CSC from 2006 to 2012 and 643 strokes/TIA's transported directly to the PSC. Differences inLength of stay (LOS), frequency of in-hospital mortality/discharge to hospice and major complications (respiratory failure, infection, DVT, PE, MI or recurrent stroke in house) were calculated.

Results:
The PSC lost an average of 3.69 patients to the CSC each month. The 5.52 day PSC patient average LOS was similar to the bypassed CSC patient 6.00 day LOS. Approximately 1 of every 8 bypassed CSC patients (39 of 310) received Neurosurgery or Endovascular intervention not available at the PSC. Comparing PSC patients to a subset of 209 verified stroke/TIA bypassed CSC patients showed the PSC was 15 times less likely to admit a ICH that dies in hospital or is discharged to hospice (0.6%, 4 of 643) than to be bypassed with such a patient (9.6%, 20 of 209), Odds ratio =15.38, 95% CI =5.2 to 45.5, P<0.0001. The PSC was less likely to admit any stroke (ICH or ischemic) that suffered a major complication (13%, 71 of 643) than to be bypassed with such a patient (34%, 81 of 209), Odds ratio =2.54, 95% CI =1.78 - 3.62, P<0.0001.

Conclusion:
SSAET bypass was especially effective for diverting fatal ICH away from a PSC without in house Neurosurgery. The bypassed PSC was less likely to admit a strokepatient with a major complication.
Abstract 27: Sleep Apnea and Ischemic Stroke Subtype: The BASIC Sleep Project
Authors: Brown Devin L , Mowla Ashkan , McDermott Mollie , Morgenstern Lewis B , Chervin Ronald D , Hegeman Garnett , Smith Melinda A , Garcia Nelda M , Lisabeth Lynda D
Published: March 2022

Background:
Little is known about the prevalence of sleep apnea (SA) across ischemic stroke subtypes. Given the important implications for SA screening, we tested the association between SA and ischemic stroke subtype in a population-based study.

Methods:
Within the Brain Attack Surveillance in Corpus Christi Project, ischemic stroke patients were offered SA screening with the ApneaLink Plus
TM
device (n=355). A board-certified neurologist assigned TOAST subtype (with an additional category for nonlacunar infarctions of unknown etiology) using hospital records (diagnostic tests, imaging reports, discharge summaries). Unadjusted and adjusted (demographics, BMI, NIHSS, diabetes, history of stroke/TIA) logistic and linear regression models were used to test the association between subtype and SA or apnea-hypopnea index (AHI).

Results:
Median age was 65 and 55% were male; 59% were Mexican American. Median time from stroke onset to SA screen was 13 days (IQR: 6, 21). Overall, 215 (61%) had SA (AHI ≥10). Median AHI was 13 (IQR: 6, 27). Prevalence of SA by subtype was: cardioembolism, n=42/64, 66%; large artery atherosclerosis, n=13/23, 57%; small vessel occlusion, n=17/25, 68%; other determined, n=1/2, 50%; undetermined etiology, n=65/113, 58%; and nonlacunar stroke of unknown etiology, n=80/128, 63%. Ischemic stroke subtype (other determined excluded due to small numbers) was not associated with SA in unadjusted (p=0.72) or adjusted models (p=0.91) models. Ischemic stroke subtype was not associated with AHI in unadjusted (p = 0.41) or adjusted models (p=0.62).

Conclusion:
In this population-based stroke surveillance study performed in a bi-ethnic community, ischemic stroke subtype was not associated with the presence or severity of SA. Sleep apnea is likely to be present after ischemic stroke, and the subtype should not influence decisions about SA screening during inpatient hospitalizations.
Abstract 30: Association of Fluid Levels, Density Heterogeneity and Irregular Margins on Baseline Non-Contrast Computerized Tomography With Significant Hematoma Expansion in Intracerebral Hemorrhage
Authors: Blacquiere Dylan , Demchuk Andrew , al-Hazzaa Mohammed , Lum Cheemun , Rodriguez-Luna David , Molina Carlos , Silva Blas Yolanda , Dzialowski Immanuel , Czlonkowska Anna , Boulanger Jean-Martin , Gubitz Gord , Padma Vasantha , Bhatia Rohit , Roy Jayanta , Kase Carlos , Hill Michael , Aviv Richard , Dowlatshahi Dar
Published: March 2022

Introduction:
The PREDICT study confirmed that the spot sign was a valid predictor of expansion in intracerebral hemorrhage (ICH) at 24h, with a positive predictive value (PPV) of 61%. This technique requires access to computed tomography angiography (CTA). Other markers may enhance the ability to predict expansion in ICH, or be useful in cases where multimodal imaging is not available. Previous studies have suggested that markers on non-contrast computed tomography (NCCT) such as density heterogeneity within the hematoma, irregularity of external margins, or internal fluid levels are associated with hematoma expansion (HE).

Methods:
Baseline NCCT scans of patients enrolled in PREDICT were examined for the presence of internal fluid levels (defined as a change within the hematoma resulting in a linear interface between two discrete fluid densities) and for the presence of hematoma density heterogeneity and margin irregularity (using an ordinal scale of 1-5 defined, published and validated previously). The association of each marker with median 24h absolute growth and with significant HE (defined as an increase in hematoma size of 6 mL or 33% measured 24h from baseline) were determined.

Results:
Fluid levels were present in 29 (8.3%) of 351 eligible patients. The presence of fluid levels were associated with significant HE at 24h (χ2 =7.64, df=1, p<0.01) and with a trend toward increased median absolute ICH volume at 24h (6.4 mL vs. 0.9 mL, p=0.09). The PPV for fluid levels was 52% (95% CI 46-57) for significant HE. Increased density heterogeneity (p<0.01) and margin irregularity (p<0.01) were both associated with increased median absolute ICH volume at 24h. Increased density heterogeneity was associated with significant HE (χ2 =20.0, df=4, p<0.01); increased margin irregularity had a trend toward association with significant HE (χ2 =8.69, df=4, p=0.06).

Conclusions:
Density heterogeneity and fluid levels are associated with significant HE at 24h, and margin irregularity is associated with increased median hematoma size. These markers may be useful for predicting significant HE in ICH in cases where CTA is unavailable to identify the presence of a spot sign. They may also provide additional variables to incorporate into risk scores for hematoma expansion.
Abstract 31: Ultraearly Hematoma Growth: Multicenter External Validation of the Adjustment of Intracerebral Hemorrhage Volume by Onset-to-imaging Time
Authors: Rodriguez-Luna David , Rubiera Marta , Dowlatshahi Dar , Coscojuela Pilar , Aviv Richard I , Silva Yolanda , Dzialowski Imanuel , Lum Cheemun , Czlonkowska Anna , Boulanger Jean-Martin , Kase Carlos S , Gubitz Gord , Bhatia Rohit , Padma Vasantha , Roy Jayanta , Hill Michael D , Demchuk Andrew M , Molina Carlos A ,   PREDICT/Sunnybrook ICH CTA study group
Published: March 2022

Background:
The impact of baseline intracerebral hemorrhage (ICH) volume on hematoma growth (HG) and clinical outcome may vary widely depending on the onset-to-imaging time (OIT). We previously reported that the adjustment of initial ICH volume by OIT (coined as ultraearly HG, uHG) is a powerful tool for outcome prediction in acute ICH. We aimed to validate our previous findings in a multicenter external cohort and to assess the relationship between uHG and the CTA spot-sign.

Methods:
The PREDICT study was a prospective, observational cohort study of consecutive ICH patients <6 hours. Patients underwent baseline and 24-hour CT scans, and CTA for the blinded detection of spot sign. uHG was defined as the relation between baseline ICH volume/OIT, HG as hematoma expansion >33% or >6 mL, early neurologic deterioration (END) as increase ≥4 points in the NIHSS score or death at 24 hours, and poor outcome as mRS score >2 at 3 months.

Results:
Two hundred and thirty-seven patients were included in this study. Median baseline ICH volume was 14.5 (6[[Unable to Display Character: –]]30.4) mL, median OIT 135 (85.5[[Unable to Display Character: –]]199) minutes, and median uHG 6.5 (2.5-14.3) mL/h. The spot sign was present in 31.2% of patients. uHG was 2.7-fold higher in spot sign-positive patients (11.1 [5.7-17.7] mL/h vs. 4.1 [1.9-12.3] mL/h, P<0.001). uHG >4.7 mL/h improved the sensitivity-specificity of both baseline ICH volume >10 mL and spot sign in the prediction of HG (73.9%-57.5% vs. 68.1%-54.3% and 48.9%-73.9%), 90-day mortality (82%-56.3% vs. 78%-53.5% and 45.8%-70.8%), and poor outcome (72.9%-80.4% vs. 69.8%-70.6% and 38%-75%), respectively. The median hematoma expansion at 24 hours among spot-positive patients was 3.2 mL in uHG <5 mL/h group, 4.1 mL in uHG 5-10 mL/h group, and 4.8 mL in uHG >10 mL/h group (P<0.001). In adjusted multivariate analyses uHG independently predicted HG (OR 1.08, 95% CI 1.04-1.12), END (OR 1.06, 95% CI 1.02-1.10), 90-day mortality (OR 1.07, 95% CI 1.02-1.11), and poor outcome (OR 1.12, 95% CI 1.02-1.23).

Conclusions:
These results validate uHG as a powerful predictor of outcome in acute ICH. uHG is significantly higher in spot sign patients, improves the accuracy of baseline ICH volume and spot sign in the prediction of HG and clinical outcome, and independently predicts HG, END, 90-day mortality, and poor outcome.
Abstract 43: Increased Activation of Inflammatory Genes in Monocytes of Healthy People with Ischemic White Matter Disease
Authors: Nyquist Paul A , Talbot Conover , Bilgel Murat , Yanek Lisa R , Becker Lewis r C , Cuzzocreo Jennifer L , Mathias Rasika , Berger Alan , Cheadle Chris , Becker Diane M
Published: March 2022

Introduction:
White matter hyperintensities (WMH) on MRI represent small vessel ischemic cerebrovascular disease. Greater WMH burden is associated with higher levels of circulating inflammatory cytokines in persons > 65 years with dementia, suggesting a pro-inflammatory vascular process. We hypothesized that middle-aged, asymptomatic, apparently healthy high risk people with high WMH burden would demonstrate increased inflammatory gene expression in monocytes analyzed with microarray.

Methods:
Subjects (N=70) were identified from a larger MRI study in 593 healthy family members of persons with early-onset CAD (< 60 years). We obtained monocytes and examined gene expression in all subjects (mean age 58.1 ± 10 years, range 30-73; 55% female; 36% African American). These included 35 subjects with the greatest WMH burden using volumetric methods in the larger study, and 35 unrelated age-sex-race matched controls with the lowest WMH burden. Monocyte mRNA was analyzed on Illumina Human HT12 v4 microarrays. We performed unsupervised principal component analysis (PCA) followed by ANOVA between high and low WMH groups. Genes with 2 SD differences in expression between groups were included for Gene Ontology permutation analysis using 1000 permutations within “GoMiner”. Only genes with the lowest false discovery rate (FDR) were summarized.

Results:
PCA identified no significant clustering. A total of 1,315 genes were included in gene ontology analysis and resulted in 10 ontological categories with an FDR<0.01%. This included 164 genes all showing greater expression in the high WMH group. These were key inflammatory genes, such as tumor necrosis factor (TNF), interleukin-6 (IL-6), interleukin-8 (IL-8), toll like receptor 5 and 7 (TLR5, TLR7) and integrin alpha 5 and M (ITGA5, ITGAM).

Conclusions:
Gene microarray ontological analysis of monocytes in healthy middle aged high risk people with greater WMH burden shows increased activation of genes of known innate inflammatory pathways. These findings likely reflect greater pro-inflammatory processes in persons with greater WMH, consistent with the presence of inflammation-mediated occult small vessel cerebrovascular disease in a healthy middle-aged population at increased risk for vascular diseases.
Abstract 45: Carotid Intima-Media Thickness is Associated with White Matter Hyperintensity Volume:
The Northern Manhattan Study
Authors: Markert Matthew S , Dong Chuanhui , Della-Morte David , Roberts Eugene , Bartels Susanne , Sacco Ralph L , Elkind Mitchell S , Wright Clinton B , Rundek Tatjana
Published: March 2022

Background:
White matter hyperintensities (WMH) have been associated with increased risk of stroke, cognitive impairment and dementia. WMH may be a manifestation of small vessel disease although their pathophysiology remains unknown. We sought to evaluate the relationship between carotid intima-media thickness (cIMT), a subclinical ultrasound imaging marker of vascular disease, and WMH measured from brain MRI in a multi-ethnic, stroke-free community-based cohort.

Methods:
As a part of population based Northern Manhattan Study, we evaluated a group of stroke and myocardial infarction - free individuals who had brain MRI and high-resolution carotid ultrasound performed. We used linear and logistic regression to examine the effect of continuous measures of cIMT on quantitatively derived WMH volume (WMHV) while adjusting for age, sex, race-ethnicity, hypertension or diastolic blood pressure, diabetes, body-mass index, plasma total cholesterol, LDL, HDL, and a history of smoking.

Results:
Among 1140 participants (mean age: 70.6±9.0, 61% women, 15% White, 16% Black, 59% Hispanics) the mean cIMT was 0.89 ± 0.14mm and WMHV 0.68 ± 0.84. In a multivariable linear model, increase in log-cIMT was significantly associated with increase in log-WMHV (β=0.41, p=0.0018).

Conclusion:
Increased cIMT may be a marker of increased WMHV independent of demographics and traditional vascular risk factors, contributing to the vascular mechanism of white matter disease. Therefore, carotid ultrasound may be an effective tool for assessing the risk of increased white matter disease in its pre-clinical stage.
Abstract 48: Cd73 Regulation of Netrin-1 Expression in Brain Ischemia
Authors: Petrovic-Djergovic Danica , Chong Wen , Ahmed Ahtasham , Sutton Nadia R , Kanthi Yogendra , Liao Hui , Pinsky David J
Published: March 2022

Focal cerebral ischemia is accompanied by inflammation, which further exacerbates injury. CD73 is an ectoenzyme with 5’-nucleotidase activity, which generates anti-inflammatory adenosine, from precursor AMP. In the CNS, CD73 is located on the choroid plexus cuboidal epithelium and on leptomeninges, two critical entry ports for anti- (M2) and pro-inflammatory (M1) macrophages, respectively. We previously showed that acute brain ischemia (48h) in CD73
-/-
mice resulted in larger infarct volumes related to greater influx of M1 macrophages.

Netrin-1 (Ntn-1) is secreted protein with leukorepulsive and neurite outgrowth- promoting properties. We hypothesized that macrophage influx is regulated by CD73 through its modulation of Ntn-1 expression after stroke.

We examined the Ntn-1 expression in acute (24h) and delayed phases (7days) after induction of brain ischemia in wild type (WT) and CD73
-/-
mice after photothrombotic middle cerebral artery occlusion.

We demonstrated that Ntn-1 mRNA and protein expression was induced during the acute phase of brain ischemia, and suppressed in the delayed phase in WT compared to CD73
-/-
mice. Netrin-1 mRNA expression at the 24 hr time point was higher in WT vs CD73
-/-
mice (2.7 ± 0.2 vs 1.4 ± 0.4, respectively, p<0.05). However, 7 days following brain ischemia, Ntn-1 protein expression was suppressed in WT compared to CD73
-/-
mice (0.4 ± 0.1 to 0.9 ± 0.2; p<0.03 respectively). In CD73
-/-
mice, mRNA for CCR2 and IRF5 , were upregulated at day 7, whereas IRF4 the major polarization transcription factor for anti-inflammatory macrophages, was downregulated.

These findings are consistent with the hypothesis that in acute stroke, CD73 acts to suppres influx of pro-inflammatory macrophages through induction of chemorepulsive Ntn-1 protein, but promotes influx of reparative macrophages by suppressing Ntn-1 expression at delayed phase of stroke. Our data are the first to identify a potential link between CD73 and Ntn-1 expressions in the ischemic brain, underscoring CD73 as an important modulator of the immune inflammatory response in stroke.
Abstract 49: Deletion of Mirna 17-92 in Cerebral Endothelial Cells Induces Disruption of BBB
Authors: Zhang Ruilan , Chopp Michael , Roberts Cynthia , Teng Hua , Wei Min , Zhang Li , Wang Xinli , Liu Xianshuang , Zhang Zheng Gang
Published: March 2022

Background:
The MicroRNA 17-92 (miR17-92) cluster regulates endothelial homeostasis. However, the effect of the miR17-92 cluster in cerebral endothelial cells on blood brain barrier (BBB) has not been investigated. We examined BBB integrity in a transgenic mouse line in which miR17-92 cluster is ablated in endothelial cells.

Methods and Results:
Adult Tie2-Cre:miR17-92 flox/flox (Tie2/miR17-92) mice and Tie2-Cre:Tomato (Tie2/red) reporter mice were used. Cerebral vessels in Tie2/red reporter mice exhibited red fluorescence, indicating specific expression of Tie2 in cerebral endothelial cells. RT-PCR analysis revealed ~70% reduction of miRNA levels of individual members of the miR17-92 cluster in endothelial cells harvested from Tie2/miR17-92 mouse brain, confirming deletion of the miR17-92 cluster. Time-lapse microscopic analysis of cultured endothelial cells showed a substantial reduction of capillary formation by miR17-92 cluster knockout endothelial cells compared to the cells harvested from Tie2/red reporter mice. In vivo, analysis of 3D cerebral microvessels showed that ablation of the miR17-92 markedly (P<0.05) increased capillary diameter in the cortex (7.1±0.4μm vs 5.1±0.3μm in reporter, n=4 mice/group), corpus callosum (CC, 6.6±0.4 vs 4.7±0.3), and striatum (6.7±0.4 vs 5.0±0.3). Triple immunofluorescent staining showed that the absence of this cluster substantially (p<0.05) reduced pericytes identified by platelet-derived growth factor-β positive cells (32±6 cells vs 80±6 cells in cortex, 34±7 vs 77±6 in CC, and 36±6 vs 79±5 in striatum) and decreased astrocyte end-foot processes identified by aquaporin 4 positive cells (42±6 cells vs 72±6 cells in cortex, 40±10 vs 70±6 in CC, and 36±6 vs 65±8 in striatum). These data suggest that cerebral endothelil cells lacking miR17-92 causes disruption of vascular coverage by pericytes and astrocyte end-foot processes. Deletion of the miR17-92 cluster also increased extravasation of Evans blue dye into the parenchyma and reduced the number of doublecortin positive neuroblasts in the subventricular zone.

Conclusion:
Our data indicate that ablation of the miR17-92 cluster in cerebral endothelial cells disrupts BBB integrity, which could exacerbate ischemic damage.
Abstract 5: Dynamic Perfusion Assessment of Collateral Blood Flow in MCA Occlusion as Indicator of Tissue Fate
Authors: Villringer Kersten , Serrano Sandoval Rafael A , Ostwaldt Ann-Christin , Brunecker Peter , Rocco Andrea , Rocco Andrea , Fiebach Jochen B
Published: March 2022

Objective:
M1 occlusions with concomitant large cortical infarcts can result in life long severe disabilities. Therapeutic decisions for iv thrombolysis only or bridging to endovascular treatment require sufficient information of collateral flow. Hence, we tried to evaluate the potential of dynamic perfusion in the assessment of collateral flow with respect to tissue fate and outcome.

Method:
Between 1/2009 until 1/2012 ninety patients with MCA infarcts due to M1 occlusions were examined in a 3 T MR scanner. Selection criteria were DWI, PI, MR angiography, NIHSS on admission; FLAIR, MR angiography day 6 and mRS day 90, which left 30 patients for further evaluation. For evaluating dynamic perfusion the second previous image was subtracted from each frame of the raw perfusion data and the final images were assessed according to Higashida′s scale (Stroke 2003;34: e109-37). Rapid collateral flow was defined as arrival of signal drop in the ischemic side before the last arterial phase signal in the unaffected side. The ischemic region was monitored for complete or incomplete filling and flow direction.

Results:
Collateral flow was inversely correlated with infarct size on day 1 (p=0.005) and day 6 (p=0.006) as well as infarct growth (p=0.025) indicating collateral flow can influence infarct development. Collateral grade was significantly better in proximal M1 occlusions than in distal ones (p<0.001), however the capillary filling was significantly delayed (p<0.001). Mismatch volume was found to directly correlate with the delay of capillary filling (p=0.015) but not with infarct growth (p=0.064) or infarct size on day 6 (p=0.15). Higher NIHSS was directly correlated with capillary delay (p=0.042) and inversely correlated with collateral grade (p=0.027). mRS at day 90 correlated inversely with collateral grade (p=0.027), directly with infarct size on day 1 (p=0.006) and day 6 (p=0.011) demonstrating good collateral flow beneficial for tissue survival.

Conclusion:
Dynamic perfusion can provide additional information of collateral flow and capillary delay, which showed strong associations with infarct size and infarct growth, as well as clinical scores, such as NIHSS and mRS at follow-up. It can add to the assessment of tissue fate before therapy decision.
Abstract 53: Recurrent Stroke in the Warfarin versus Aspirin in Reduced Ejection Fraction (WARCEF) Trial
Authors: Pullicino Patrick , Thompson J.L.P. , Sacco Ralph L , Mann Douglas , Di Tullio Marco , Sanford Alexandra , Qian Min , Buchsbaum Richard , Levin Bruce , Mohr J.P. , Homma Shunichi ,   for the WARCEF Investigators
Published: March 2022

Background:
WARCEF randomized 2305 patients in sinus rhythm with ejection fraction (EF) ≤35% to warfarin (INR 2.0-3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. We here explore IIS rates in WARCEF patients with and without baseline stroke to determine if a subgroup with an IIS rate high enough (3-5 per 100 patient-years [PY]) to give a clinically relevant warfarin effect can be identified.

Methods:
We compared the IIS rate between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS , by comparing IIS rates between different levels of each potential risk factor. For EF we tried cut-off points of 10%, 15% and 20%. 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. Missing values were assigned the modal value.

Results:
Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2048 (3.1%) without had IIS. IIS rates in patients with baseline stroke were significantly greater compared to patients without (rate ratio 2.67; 2.37 per 100PY and 0.89 per 100PY, respectively, p=0.0004). Fourteen of 219 (6.4%) patients with EF<15% and 70 of 2079 (3.4%) with EF ≥15% had IIS. IIS rates in patients with EF<15% and patients with EF ≥15% were 2.04 per 100PY and 0.95 per 100PY, respectively (p=0.012). IIS rate in patients with baseline stroke and EF<15% was 5.88 per 100PY. In the multiple Poisson regression analysis only stroke at baseline (p=0.0001) and EF<15% vs. ≥15% (p=.005) remained significant predictors of IIS.

Conclusions:
In a WARCEF exploratory analysis, prior stroke and EF<15% were risk factors for IIS. A clinically relevant stroke risk reduction might be obtainable with warfarin in HF patients with prior stroke and EF<15%.