bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W P81: Intracranial Aneurysms and Their Relationship to Circle of Willis Variations: A Retrospective Analysis of Patients in a University Hospital
Authors: Anand Dhanya , Cordina Steve M
Published: July 2021

Background:
Cerebral aneurysms, their rupture and resultant neurological sequelae are a major cause of morbidity and mortality. Multiple studies have analyzed the etiology of cerebral aneurysms including hemodynamic and congenital factors. Since the arterial supply of the brain develops entirely from the third pharyngeal arch and the dorsal aorta, any insult to the developing vascular system increases the probability of development of variations, including aneurysms. Purpose: To identify the association of arterial variations with aneurysms. Methods: A total of 83 patients with 106 intracranial aneurysms diagnosed by cerebral angiography from January 2011 to July 2014 were analyzed for variations in the intracranial vasculature. The type and laterality of the vascular variants in relation to the aneurysms were also examined. Results: On evaluation of the aneurysms, 65 (61.3 %) had associated variations in the intracranial vasculature. Among these, 51 (78.5 %) had variations ipsilateral to the aneurysm. 90 (84.9%) were in the anterior circulation. 52 patients (62.7%) were female. Various vascular variations including hypoplasia of posterior communicating (P-Comm) artery (56.5 %), variant anterior cerebral (ACA) artery (17.39%), fetal type posterior cerebral (PCA) artery (21.7%), fenestration of vertebral artery (1.4%), superior cerebellar artery duplication (1.4%) and arteriovenous malformations were noted. Fetal type PCAs were significantly more common in patients with anterior communicating (A-comm) (p-value <0.0115) and P-Comm A aneurysms (p-value <0.0131). Also, variations of A1 segment of ACA were significantly more common in A-Comm aneurysms (p-value <0.0013). Conclusions: The distribution of aneurysms in the intracranial vasculature in our study is comparable to previous literature. Among the arterial variations we found that fetal type PCAs are significantly common among A-Comm and P-Comm aneurysms. Also, variations in the A1 segment of ACAs were commonly associated with A-Comm aneurysms. Although further conformation of these associations is required with a prospective randomized control trial, if established, screening for these variations could help in primary prevention and early treatment of these aneurysms.
Abstract W P91: The Presence of Asymptomatic Lacune Predicts Stroke Progression after Acute Cerebral Infarction
Authors: Park Moo-seok , Kim Jeong-Min , Park Kwang-Yeol
Published: July 2021

Background:
The prediction of stroke progression after acute cerebral infarction is important for clinician to determine high risk patient group for close observation and proactive management. We sought to find imaging biomarker which predicts neurological deterioration after acute cerebral infarction.

Methods:
Between January 2008 and June 2013, those acute infarction patients who admitted Chung-Ang university hospital within seven days after symptom onset were eligible to be included. We selected the patients who had been through both brain CT angiography and brain MR imaging (MRI) including susceptibility weighted image and FLAIR. The presence of white matter hyperintensity, asymptomatic lacune, and cerebral microbleed were assessed from initial brain MRI, and intracranial vascular calcification was analyzed from both intracranial internal carotid arteries by brain CT angiography. Stroke progression was defined as two or more National Institutes of Health Stroke Scale progression during admission. Univariate analysis followed by multivariate logistic regression analysis was performed to find independent imaging parameter which predicts stroke progression.

Results:
A total of 724 patients were included in the study period. Univariate analysis showed that severe calcification involving both distal internal carotid artery more than 1 centimeter and/or 50% of vessel diameter (p=0.006), white matter hyperintensity with Fazekas grade 3 (p=0.007), and asymptomatic lacune (p=0.013) is associated with stroke progression. Multivariate logistic regression analysis adjusted with age>70 years, gender, atrial fibrillation smoking, and high sensitive C-reactive protein disclosed that asymptomatic lacune is an independent predictor of stroke progression after acute cerebral infarction (odds ratio=1.76, confidence interval=1.03-3.02 p-value=0.039).

Conclusion:
Our study showed that the presence of asymptomatic lacune is an independent imaging biomarker associated with neurological deterioration after cerebral infarction.
Abstract 120: Cortical Superficial Siderosis in Community-dwelling Subjects: The Framingham Heart and Rotterdam Studies
Authors: Shoamanesh Ashkan , Akoudad Saloua , Himali Jayandra H , Beiser Alexa S , DeCarli Charles , Seshadri Sudha , Ikram M. A , Romero Jose R , Vernooij Meike W
Published: July 2021

Background:
Cortical superficial siderosis (cSS) is increasingly recognized as an imaging marker of cerebral amyloid angiopathy (CAA) in clinical settings. In these hospital-based cohorts, cSS seems to be a robust indicator of increased risk of future intracerebral hemorrhage (ICH). cSS is also described in community-dwelling individuals, but current understanding of underlying pathology and prognostic implications in this setting is limited. We characterized cSS, its determinants and consequences, compared with another MRI marker of CAA (lobar cerebral microbleeds [CMBs]) in community-dwelling older adults by combining individual-level data from two large population cohorts.

Methods:
We evaluated cSS in Framingham Original/Offspring Cohort and Rotterdam Study participants ≥ 55 years of age who underwent brain MRI allowing for cSS and CMB detection. In cross-sectional analysis, we compared vascular risk factors/medications, MRI markers of interest, apolipoprotein E (APOE) genotypes (ε3/ε3 as control), and clinical outcomes (ICH, ischemic stroke, transient ischemic attack, and mild cognitive impairment) amongst participants with cSS and those without cSS/CMBs, as well as individuals with strictly lobar CMBs (without cSS).

Results:
cSS was present in 0.4% (26) of 6049 participants and strictly lobar CMBs in 13% (776). In comparison to participants with neither cSS nor CMBs and to those with strictly lobar CMBs, participants with cSS were older (OR per year increase 1.1, 95% CI 1.1-1.1 and 1.1, 1.0-1.1, respectively), and had overrepresentation of APOE ε4 (at least 1 ε4 allele; age/sex adjusted OR 5.23, 2.1-13.3 and 3.5, 1.4-9.0), and ICH (42, 7-251 and 31, 3.8-253). There also existed a trend toward overrepresentation of the APOE ε2 allele in participants with cSS (2.8, 0.9-8.8, p=0.08 and 2.7, 0.8-8.5, p=0.10). The association with ICH withstood additional adjustment for white matter hyperintensity volume and lacunes on MRI.

Conclusions:
In this large population-based study of cSS, the prevalence of cSS was low but presence of cSS was more strongly associated with markers of CAA, such as APOE genotype and ICH, than presence of lobar microbleeds without cSS, suggesting that cSS may reflect advanced CAA even in community-dwelling subjects.
Abstract 134: Postoperative Atrial Fibrillation and the Short-term Risk of Ischemic Stroke
Authors: Gialdini Gino , Merkler Alexander E , Lerario Michael P , Kummer Benjamin R , Khormaee Sariah , Navi Babak B , Iadecola Costantino , Kamel Hooman
Published: July 2021

Introduction:
We have recently shown an association between new-onset postoperative atrial fibrillation (AF) and the long-term risk of ischemic stroke after noncardiac surgery. However, the degree of stroke risk with AF in the postoperative setting remains unclear.

Hypothesis:
New-onset postoperative AF is associated with an increased risk of ischemic stroke in the 30 days after surgery.

Methods:
Administrative claims data from all discharges at nonfederal acute care hospitals in California, New York, and Florida were used to identify patients who underwent inpatient surgery in 2007-2012. Our predictor variable was new-onset AF, defined using validated
ICD-9-CM
diagnosis and present-on-admission codes. Patients with prior stroke or AF were excluded. The outcome was postoperative stroke, defined as ischemic stroke occurring within 30 days of surgery. Cox proportional hazards analysis was used to examine the association between postoperative AF and stroke while adjusting for demographics and vascular risk factors. In sensitivity analyses, we limited the outcome to stroke occurring after discharge but within 30 days of surgery. Cardiac and noncardiac surgeries were analyzed separately.

Results:
Among 7,139,472 patients with inpatient surgery, 102,831 (1.44%) developed postoperative AF and 17,117 (0.24%) developed a postoperative stroke. After noncardiac surgery, the 30-day cumulative risk of stroke was significantly higher in those with postoperative AF (2.07%) than those without AF (0.18%). This difference was significant after adjustment for demographics and potential confounders (hazard ratio [HR], 4.3; 95% CI, 4.1-4.6). After cardiac surgery, postoperative AF was also associated with an increased cumulative risk of stroke (2.27%) compared to those without AF (1.17%), but the strength of association (HR, 1.8; 95% CI, 1.6-1.9) was less marked than in the setting of noncardiac surgery (
P
value for interaction <0.001). Postoperative AF was associated with stroke occurring after discharge and within 30 days of noncardiac surgery (HR, 1.9; 95% CI, 1.6-2.3), but not cardiac surgery (HR, 1.1; 95% CI, 0.9-1.3).

Conclusions:
Postoperative AF is associated with an increased short-term risk of stroke after noncardiac surgery.
Abstract 143: Exosomal miRNA Profiling Following Ischaemic Stroke: Clinical and Pre-clinical Data
Authors: van Kralingen Josie C , Ord Emily , Martin Hannah , Breen Christopher R , Cordiner James , Sigfridsson Emma , McCabe Christopher , Macrae I M , Dawson Jesse , Work Lorraine M
Published: July 2021

Introduction:
MicroRNA (miRNA) profiles are altered in patients with stroke. Recently, active inter-cellular transport of miRNAs in extracellular vesicles (EV), such as exosomes has been shown. We assessed whether miRNAs packaged in EVs differed in patients with stroke and patients without stroke and then performed
in vitro
and
in vivo
experiments to assess potential significance of dysregulated miRNAs.

Methods:
We recruited patients with suspected stroke. Serum was obtained at 48h post-stroke. EVs were isolated from 200μL serum before RNA extraction. A miRNA microarray was performed (Openarray™ platform) (39 patients) to identify significantly dysregulated miRNAs in stroke vs non-stroke patients. Results were validated by Taqman™ real time quantitative polymerase chain reaction of specific miRNA (17 miRNAs, 169 patients).
I
n vitro
studies of selected miRNAs were performed on a rat neuronal cell line (B50) and a rat glial cell line (B92) subjected to 9h hypoxia (1% O
2
) and serum starvation with 24h reoxygenation in complete media (n=4-5/group).
In vivo
, total miRNA expression was quantified in serum (n=4) and in peri-infarct tissue of adult spontaneously hypertensive stroke-prone rats (SHRSP) following 45min transient middle cerebral artery occlusion (tMCAO) (n=6/group).

Results:
The microarray identified 26 dysregulated miRNAs in stroke patients. Using Taqman™ levels of miRNAs 17, 20b and 93 were observed to be significantly (p<0.05) increased in stroke vs non-stroke patients. Patients with small vessel disease consistently had the highest levels.
In vitro
, a trend towards increased exosomal expression of miRNAs-17, 93 and 20b in B50 hypoxic cells was in contrast to small changes in total cell miRNA expression (vs. normoxic cells).
In vivo
, tMCAO did not induce significant modulation of miRNAs 17, 93 or 20b expression in SHRSP brain either 24h or 72h post-tMCAO. EVs isolated from the serum showed a significant increase in miRNA-93 expression at 72h post-tMCAO (p<0.05 vs. sham animals).

Conclusions:
We have identified and validated changes in EV packaged miRNA expression in patients with stroke, particularly in small vessel disease. Our pre-clinical experiments corroborate the human data and support a functional role for these findings.
Abstract 16: Temporal Changes in Hemodynamics in Patients With Vertebrobasilar Disease: Results From the Prospective Multicenter VERiTAS Study
Authors: Amin-Hanjani Sepideh , Derdeyn Colin P , Du Xinjian , Rose-Finnell Linda , Pandey Dilip K , Richardson DeJuran , Elkind Mitchell S , Zipfel Gregory J , Liebeskind David S , Silver Frank L , Kasner Scott E , Gorelick Philip B , Charbel for the VERiTAS Study Group Fady T
Published: July 2021

Introduction:
The role of regional hypoperfusion as an important contributor to stroke risk in atherosclerotic vertebrobasilar (VB) disease has recently been confirmed by the observational Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) Study. We examined the stability of hemodynamic status over time and relationship to stroke risk in patients followed in this prospective cohort.

Methods:
VERiTAS enrolled patients with recent VB TIA or stroke and ≥50% atherosclerotic stenosis or occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative MRA, and patients were designated as low flow or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of VB territory stroke. QMRA imaging was repeated at 6, 12 and 24 months. Flow status over time was examined relative to baseline, and relative to subsequent stroke risk using survival analysis.

Results:
Of 72 enrolled subjects, 50, 45 and 28 had follow-up QMRA at 6, 12 and 24 months respectively. 18 (25%) were characterized as low flow at baseline, 10% at 6 m, 20 % at 12m and 11% at 24m. Over 18±7months of follow-up, 7 of the 12 low flow patients (58%) with follow-up imaging had improved their flow status (low to normal) while only 3 of 44 normal flow patients (7%) had worsened. Baseline flow status has previously been demonstrated to be an independent stroke risk predictor; flow status at latest follow-up and prior to event remained a strong predictor of subsequent stroke (HR 4.9, CI 1.4 to16.9, p=0.01).

Conclusions:
There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic VB disease; improvement, likely attributable to development of collateral supply, was evident more frequently than worsening, presumably due to progression of disease. Flow status, both at baseline and over time, remains a robust risk factor for subsequent stroke, thus serving as an important prognostic marker.
Abstract 164: Specific Point-of-Care Testing of Coagulation in Patients Treated With Non-Vitamin K Antagonist Oral Anticoagulants Part I (SPOCT-NOAC I)
Authors: Härtig Florian , Peter Andreas , Spencer Charlotte , Ebner Matthias , Zürn Christine S , Peveto Theresa , Pearman David , Spencer Jeffrey , Blumenstock Gunnar , Kuhn Joachim , Birschmann Ingvild , Ziemann Ulf , Poli Sven
Published: July 2021

Introduction:
Non-vitamin K antagonist oral anticoagulants (NOAC) are increasingly replacing vitamin K antagonists for prevention of thromboembolism in atrial fibrillation (AF) and venous thrombosis. Ischemic stroke rate in NOAC-treated AF-patients is 1-2% per year. Subsequently, stroke physicians face a growing number of NOAC-treated patients with acute stroke. Rapid assessment of coagulation in NOAC-treated patients is vital prior to thrombolysis, but existing point-of-care testing (POCT) is suboptimal. For the first time we evaluate NOAC-specific POCT.

Hypothesis:
Ecarin clotting time (ECT)- and anti-Xa activity-POCT accurately predict plasma concentrations of dabigatran and apixaban/edoxaban/rivaroxaban.

Methods:
80 patients receiving first NOAC-dose and 80 already on NOAC-treatment will be enrolled (N=40 for each NOAC). Subjects receiving other anticoagulants will be excluded. 6 blood samples will be collected from each patient: before drug intake, 30min, 1, 2, and 8h after intake, and before next dose. NOAC-concentrations will be measured by mass spectrometry.

Results (preliminary):
Until now 138 blood samples of 23 dabigatran-treated patients were analyzed. Dabigatran-concentrations ranged from 0-371ng/mL. ECT-POCT ranged from 20-219s. Pearson’s correlation coefficient showed strong correlation for ECT-POCT and dabigatran-concentrations (r=0.94, p<0.001). Dabigatran-concentrations >50ng/mL (threshold for thrombolysis according to expert recommendation) were detected by ECT-POCT (>50s) with 100% sensitivity and 82% specificity. Baseline-samples not containing any dabigatran yielded normal ECT-POCT.

Conclusions:
This is the first study evaluating NOAC-specific POCT. Preliminary results show excellent correlation for ECT-POCT and dabigatran; relevant dabigatran-concentrations were detected in 100%. More pioneering results on NOAC-specific POCT will be presented.
Abstract 18: Defining Clinical Presentation, Imaging Findings, and Management of Intracranial Fibromuscular Dysplasia: a Single Center Experience
Authors: Cerejo Russell , Brinza Ellen K , Donohue Megan M , Fendrikova-Mahlay Natalia , Hussain Muhammad S , Toth Gabor , Uchino Ken , Bain Mark , Rasmussen Peter , Kim Esther S , Gornik Heather L
Published: July 2021

Introduction:
Intracranial (IC) artery involvement in fibromuscular dysplasia (FMD) may manifest as stenosis, dissection, or cerebral aneurysm. We sought to identify clinical, imaging, and treatment characteristics of FMD patients with IC manifestations.

Methods:
Analysis of prospectively collected data from a single center of the US FMD patient registry with additional medical record and imaging review. Patients were consented for enrollment if FMD was confirmed by imaging in at least one vascular territory.

Results:
From 2/2/2009-7/10/2015, 474 FMD patients were enrolled in the registry. Of the 421 patients with IC arterial imaging, 52 (12.4%) had IC FMD, with catheter angiography available in 29 (55.8%) patients. Median age of initial FMD symptoms was 47 years (IQR 38 - 55) and 51 patients were female. Concomitant extracranial (EC) carotid FMD was present in 92.3%, vertebral FMD in 48.9%, and renal FMD in 50.0%. Among 52 patients with IC FMD, 41 (78.8%) had IC aneurysm (9.7% of entire cohort with IC imaging), 7 (13.5%) had IC dissection, 6 (11.5%) had focal IC stenosis, and 2 (3.8%) had multifocal IC FMD. Fifteen patients with IC FMD (28.8%) were symptomatic (9 TIA/ischemic stroke, 2 hemorrhagic stroke, 4 isolated cranial neuropathy). Among patients with IC FMD, 22 (42.3%) required intervention. Treatment included EC-IC carotid artery bypass in 2 patients, aneurysm coiling in 13, aneurysm clipping in 9, and IC stenosis stenting in 1 patient. At the time of last follow-up, 47 patients (90.4%) were treated with an anti- platelet agent.

Conclusion:
In a single center cohort, 12.4% patients with FMD had IC involvement. Arterial aneurysm was the most common manifestation followed by dissection and stenosis. Aneurysm was present in 9.7% of patients who underwent IC imaging, highlighting the importance of comprehensive vascular assessment of patients with FMD.
Abstract 26: RACE to Treat Stroke
Authors: Korsnack Andrea M , Adams Andrea
Published: July 2021

Background:
Endovascular treatment was shown to drastically improve stroke patient outcomes but earlier identification of eligible patients is crucial. First responders are instrumental to the rapid identification and transportation of stroke patients to the nearest appropriate facility for acute stroke care especially when endovascular intervention is an option.

Purpose:
To develop and evaluate the effectiveness of an algorithm for first responders to use to differentiate which stroke patients should be transported to the closest Interventional Stroke Center for treatment.

Method:
We revised the County-Level Emergency Medical Services (EMS) protocol and algorithm to include the Rapid Arterial oCclusion Evaluation (RACE) scale in addition to the Cincinnati Prehospital Stroke Scale (CPPS). Together these simple in-the-field scales assess stroke severity and identify patients with acute stroke and large artery occlusion in a prehospital setting. Lucas County EMS staff received a four hour block of continuing education with credit on acute stroke, the updated protocol and algorithm, and use of the new RACE scale in addition to the CPPS. Effectiveness of the training and use of the RACE alert was measured by the percent of patients accurately identified with and without large artery occlusion.

Results:
Training was provided to 450 EMS staff in several in-person sessions in June 2015. The RACE protocol went citywide on July first. Of the 18 patients brought in to our hospital by EMS in July using the RACE protocol, 72% were identified correctly using the tool. Of these, 6 were identified correctly as having large vessel occlusions and 7 were correctly identified as not having large vessel occlusions. The remaining 5 patients transported by EMS were identified as large vessel occlusions, but were not found to have strokes (seizures, intoxication, and conversion disorders).

Conclusion:
Our data suggests that first responders can accurately differentiate between which stroke patients could benefit from endovascular treatment using a simple algorithm. Future evaluation could measure the relationship between accurate pre-hospital identification and treatment rates.
Abstract 33: Non-invasive Urinary Biomarker Levels Correlate With Preoperative Disease Status and Predict 1-year Angiographic Outcomes in Pediatric Moyamoya Patients
Authors: Giantini Larsen Alexandra , Duggins-Warf Micah , Pineda Stephen , Han Xuezhe , Smith Edward R
Published: July 2021

Introduction:
Diagnosis of moyamoya requires imaging which include risks associated with anesthesia and angiography. We describe the novel application of non-invasive urinary biomarkers to assess preoperative ischemia, development of transdural collaterals and predict 1-year angiographic outcomes from preoperative samples.

Hypothesis:
We tested the hypothesis that urinary levels of netrin-1 and vascular endothelial growth factor (VEGF) correlate with disease severity at diagnosis and prospectively identify patients better able to grow surgical collaterals, as quantified by Matsushima grade.

Methods:
Preoperative urine samples were collected from patients (age<22 years). Radiographic data (Suzuki stage, presence/location of preoperative transdural collaterals and postoperative Matushima grade) were performed by neuroradiologists and obtained from clinical records. Quantitative analysis of protein levels was performed with ELISA, normalizing for protein and subjected to statistical comparison between groups.

Results:
A total of 132 patients with moyamoya had samples and imaging for analysis. Urinary VEGF and netrin-1 levels were significantly elevated in moyamoya patients compared to matched controls (6.6 vs. 4.4pg/ug and 0.6 vs. 2.3pg/ug, p<0.05 respectively). In patients without transdural collaterals, VEGF and netrin-1 urinary levels were higher than in those with collaterals (n=68 without, 64 with, p= 0.03 netrin, NS VEGF) Higher preoperative urine levels of both VEGF and netrin-1 correlated with better postoperative Matsushima grade (n=38,29,16 for Matsushima A,B,C, p<0.01 for VEGF and p<0.05 for netrin-1).

Conclusions:
Urinary levels of VEGF and netrin-1 are elevated in moyamoya patients and may correlate with an increased angiogenic drive that is higher in patients without spontaneous collaterals (who may be more ischemic than those who have already established collaterals) and whose presence may aid in development of surgical collaterals after indirect revascularization. These experiments provide proof-of-principle data that urinary biomarkers may have utility in augmenting clinical decision-making.
Abstract 56: Plasma Vitamin D and Non-HDL Cholesterol Reflect the Disease Severity of Cerebral Cavernous Malformation
Authors: Girard Romuald , Khanna Omaditya , Jesselson Michael , Zhang Lingjiao , Shenkar Robert , Gangal Anupriya , Fam Maged , Gibson Christopher C , Whitehead Kevin J , Li Dean Y , Liao James K , Shi Changbin , Awad Issam A
Published: July 2021

Introduction and Hypothesis:
Cerebral cavernous malformations (CCMs) are common cerebrovascular anomalies with highly variable but potentially disabling disease behavior disease behavior. Factors portending an aggressive clinical course are not known. An association of disease severity with vitamin D has been suggested in preclinical studies, and other evidence supports a role of inflammation in the pathobiology of CCM.

Methods:
A prospective case-controlled study enrolled 43 consecutive patients with CCM disease (20 sporadic/solitary and 23 multifocal/familial). Non-fasting peripheral venous blood samples were analyzed for plasma levels of 25-(OH) vitamin D, high-density lipoprotein (HDL) and non-HDL cholesterol, C-reactive protein (CRP), and for leukocyte Rho-kinase (ROCK) activity. We correlated these biomarkers with prospectively defined parameters of chronic (a history of multiple adjudicated clinically overt hemorrhages, early age of clinical onset or high lesion burden in familial cases) and recent (lesional growth or hemorrhage in the preceding year, or new lesion formation in familial cases) disease aggressiveness.

Results:
Patients with historically aggressive CCM disease had significantly lower 25-(OH) vitamin D and non-HDL cholesterol levels. Neither was predictive of recent disease activity. HDL cholesterol, CRP levels and ROCK activity did not correlate with historical or recent disease severity. Receiver operating characteristic curves for 25-(OH) vitamin D or non-HDL cholesterol showed ‘fair’ accuracy: Area under curve (AUC)= 0.73 (p=0.01) and 0.74 (p=0.007), respectively. Combination of the two parameters improved the accuracy to AUC=0.80 (p<0.001).

Conclusions:
This is the first evidence of correlation of peripheral blood biomarkers with the severity of human CCM disease. Validation of these biomarkers and their potential modification may influence the clinical care of CCM.
Abstract 78: Pre-hospital Rapid Neurological Improvement in Acute Stroke Syndromes: Frequency and Clinical Outcomes
Authors: Balucani Clotilde , Levine Steven R , Sanossian Nerses , Starkman Sidney , Liebeskind David S , Stratton Samuel , Eckstein Marc , Hamilton Scott , Conwit Robin , , Saver Jeffrey L
Published: July 2021

Introduction:
There are no systematic data evaluating frequency and clinical outcome of patients with acute stroke syndromes presenting with rapid neurological improvement (RNI) in the pre-hospital setting. Our objectives were to determine frequency, magnitude, and clinical outcomes of RNI vs no-RNI.

Hypothesis:
Pre-hospital RNI predicts favorable clinical outcome as compared to no-RNI in acute stroke syndromes.

Methods:
Post-hoc analysis of The Field Administration of Stroke Therapy-Magnesium (FAST-MAG), a phase 3, randomized, double-blind, placebo-controlled clinical trial. Any-RNI was defined as a decrease of 2 or more points from the pre-hospital Los Angeles Motor Scale (PH-LAMS) to the hospital LAMS (H-LAMS), while dramatic-RNI was defined as a decrease of at least 4 points. Outcomes were: excellent recovery at 90 days (0-1 mRS), discharge disposition (home vs. not home), and death.

Results:
In the overall cohort of 1,700 subjects in FAST-MAG, frequency of any-RNI was 326 (19%), dramatic-RNI 98 (6%) and no-RNI 1,276 (75%). Mean age 71.4 (+/-13.2 SD), 67.1 (+/-13.3) and 69.1 (+/-13.6) for any-RNI, dramatic-RNI and no-RNI, respectively (p= 0.004). There was no gender difference across the 3 groups (p= 0.204). Hypertension (p=0.008) and diabetes (p= 0.014) were significantly less frequent among any-RNI and dramatic-RNI vs no-RNI. PH-LAMS medians: any-RNI: 3 (IQR 3-5), dramatic-RNI: 5 (4-5) and no-RNI: 4 (3-5), (p<.0001). Median hospital NIHSS was: any-RNI 3 (1-6), dramatic-RNI 0 (0-2) vs no-RNI 12 (6-20) (p<.0001). Any-RNI and dramatic-RNI were more likely to be discharged home (53% and 64%, respectively) vs no-RNI (25%) (p<.0001). Any-RNI (61%) was more likely to have excellent outcome vs no-RNI (28%) (p<0.0001) and after adjusting for covariates, the OR was 1.33 (95%CI 1.00-1.76, p=0.046).

Conclusions:
Frequency of pre-hospital any-RNI in the FAST-MAG cohort was almost 1 in 5 subjects, with 6% having dramatic recovery. While clinical outcomes were overall more favorable for acute stroke syndromes presenting with RNI, 47% (any-RNI) and 36% (dramatic-RNI) were not discharged home. Our data suggest that RNI in the pre-hospital setting does not always translate to favorable outcome. Factors affecting outcome in RNI need to be further explored.
Abstract TMP45: Usefulness of Susceptibility Vessel Sign With Bright Vessel Appearance in Acute Ischemic Stroke
Authors: Jeong Han-Gil , Kim Beom-Joon , Kim Chi Kyung , Kim Jun Yup , Kang Dong-Wan , Kim Do Yeon , Pyun Jung Min , Lee Seung-Hoon
Published: July 2021

Background:
Red thrombi, composed of fibrin and trapped erythrocytes, have magnetic susceptibility effect. Susceptibility vessel sign (SVS) is visualized more sensitively using susceptibility weighted imaging (SWI) than T2*-weighted imaging. Bright vessel appearance (BVA) on arterial spin labeling (ASL) imaging can visualize occluded arterial segment by arterial transit artifact, more sensitively in small and peripheral branches. We investigated the usefulness of SWI-SVS with BVA to visualize different thrombus and predict stroke mechanisms.

Methods:
From a total of 564 stroke cases who admitted to Seoul National University Hospital in 2014, the authors collected eligible cases with the following inclusion criteria; (1) Lesion-documented ischemic stroke (N=425); (2) SWI and ASL MRI performed (N=407); (3) Symptomatic arterial occlusion with BVA (N=141). All images were analyzed for the presence and location of SWI-SVS and BVA. The location of SWI-SVS and BVA were classified into (1) proximal, large arteries; distal ICA, M1/2, A1, P1, basilar artery, V4 and (2) peripheral, small arteries; M3/4, P2/3, A2/3, lenticulostriate arteries, three cerebellar arteries. The relationships between SWI-SVS in the presence of BVA and stroke etiologies are explored.

Results:
Male was 58.2% (n=82) and mean age was 65.7±14.3. Thirty-four percent (n=48/141) of BVA and 30.3% (n=30/99) of SVS was located within small, peripheral arteries. SWI-SVS was more commonly associated with other determined etiology (20.2% vs. 4.8%) and cardioembolism (39.4% vs. 14.3%), but less with large artery atherosclerosis (26.3% vs. 69.0%, P <0.01) compared to the patients without SWI-SVS. Cancer-related hypercoagulability (60%, n=12/20) was most common in other determined cases with SWI-SVS. Multivariate analysis showed that SWI-SVS was an independent predictor of other determined etiology (adjusted OR, 7.20; 95% CI, 1.48-34.99) and cardioembolism (adjusted OR, 5.76; 95% CI, 1.27-26.02)

Conclusions:
SWI-SVS with BVA may predict ischemic stroke of cardioembolism and other determined etiology. Occlusions of small, peripheral arteries are well visualized with BVA and composition of thrombus can be identified by SWI-SVS.
Abstract TMP47: The Clinical Utility of Contrast Enhanced Ultrasound Detecting Disrupted Carotid Plaques
Authors: Tonomura Shuichi , Saito Kozue , Ishibashi-Ueda Hatsue , Abe Soichiro , Mori Kota , Motoyama Rie , Yamagami Hiroshi , Kataoka Hiroharu , Takahashi Jun C , Iihara Koji , Toyoda Kazunori , Nagatsuka Kazuyuki
Published: July 2021

Introduction:
Contrast-enhanced ultrasound (CEUS) using new contrast agents which offer a stable contrast effect in vivo is a noninvasive modality to detect vulnerability of carotid plaque, ulceration and neovascularization. A recent study showed the superiority for the detection of small ulcers using CEUS to color-Doppler ultrasound (CDUS), which used computed tomographic angiography (CTA) as the reference technique.

Hypothesis:
We assumed CEUS enables us to detect disruption of carotid plaques that could not be detected by CDUS and CTA. We aimed to investigate the diagnostic accuracy for detecting the disruption of the carotid plaques comparing with histopathological findings.

Methods:
From July 2010 to July 2015, we enrolled 68 internal carotid stenosis (ICS) patients undergoing carotid endarterectomy (CEA) and preoperatively examined CEUS using Perflubutane (Sonazoid), CDUS and CTA. We compared the findings of the plaque disruptions detected by these three modalities with the histopathological findings of ulceration and present/recent plaque rupture.

Results:
Of 68 subjects (age 72±6.6years old, 66 men), 44 (64%) had symptomatic ICS. Pathologically, ulceration and present/recent plaque rupture were found in 58 cases (85.3%). The diagnostic accuracy for detecting the disruption of carotid plaque by CEUS was significantly superior to other modalities (Table 1). CEUS could find disrupted carotid plaque more accurately than CTA.

Conclusions:
The assessment of the disruption of the plaques using CEUS was well correlated with pathological findings of plaque rupture, which may help us to evaluate the plaque vulnerability in vivo real time.
Abstract TMP51: Activation of PGE2 EP1 Receptor Promotes Microglial Phagocytosis Though CD36 Receptor Recycling
Authors: MA BO , Day Jason , Phillips Harrison , Slootsky Bryan , Doré Sylvain
Published: July 2021

Background and Purpose:
We have shown that the deletion of prostaglandin E2 (PGE2) EP1 receptor undermined microglial phagocytosis in vivo. However, the related mechanism still remains unknown. CD36 is a type II scavenger receptor that mediates microglial phagocytosis. It was reported that microglial CD36 contributes to hematoma clearance after intracerebral hemorrhage (ICH). In this study, we sought to identify the effects of two EP1 agonists on microglial phagocytosis and CD36 receptor recycling in primary microglial cultures.

Method:
The EP1 agonists: 17-phenyl trinor-PGE2 (17-pt-PGE2) and ONO-DI-004 were used to treat primary microglial cultures, respectively. Fluorescent latex beads or CFSE-labeled red blood cells (CFSE-RBCs) were added to microglial cells at a concentration of ten beads/RBCs per cell for live-cell imaging. Immunocytochemistry was also performed with antibody against ionized calcium-binding adapter molecule 1 (Iba1, a marker to microglia). Furthermore, we analyzed CD36 receptor recycling by using an established receptor recycling assay.

Result:
The primary microglial cells were incubated with fluorescent latex beads and treated with the EP1 agonist 17-pt-PGE2 for 120 min. We found that 17-pt-PGE2 significantly increased the number of attached beads to microglial cells at the concentration of 10 μM from 40 min to 120 min of incubation. Furthermore, we analyzed CD36 receptor recycling using an established receptor recycling assay and the quantitative results showed that 10 μM of 17-pt-PGE2 treatment markedly increased the area of recycled CD36 receptor in microglial cells. We then treated primary microglial cells with another selective EP1 agonist ONO-DI-004 for 120 min at the concentration of 5 μM and 10 μM, respectively. The area of CFSE-RBCs after ice-cold PBS washing was markedly increased with 10 μM of ONO-DI-004 treatment. In the live-cell imaging experiment, 10 μM of ONO-DI-004 treatment also significantly increased the number of attached CFSE-RBCs to microglial cells from 25 min to 60 min of incubation.

Conclusions:
This study showed that the EP1 agonists: 17-pt-PGE2 and ONO-DI-004 can promote microglial phagocytosis in vitro and enhanced CD36 receptor recycling could mediate some of these effects.
Abstract TMP80: Relationship Between Neutrophil/Lymphocyte Ratio and Post-stroke Depression
Authors: Lucke-Wold Ann N , Regier Michael D , Petrone Ashley , Tennant Connie , Barr Taura
Published: July 2021

Background:
Depression is a leading cause of disability post-stroke. Nearly a third of stroke victims suffer from depression after event occurrence. Post-stroke depression hinders physical rehabilitation, decreases quality of life, and has a negative effect on long-term survivability. Inflammatory processes post-ischemic stroke are likely associated with the development of depression. The neutrophil-lymphocyte ratio (NLR) is a routinely available marker of systemic inflammation and could serve as a prognostic tool at hospital admission for post-stroke depression. The goal of this project was to determine the relationship between admission NLR and depression 30 and 90 days post-stroke.

Methods:
58 ischemic stroke patients were recruited from a regional primary stroke center and followed up to 90 days post stroke. NLR levels were drawn at Emergency Department admission and at 24 hours. The Quick Inventory for Depression Symptomology (QIDS) was used to measure depression symptoms at 24 hours, 30 days and 90 days post stroke. We scaled continuous variables by their standard deviation and used the Box-Cox or exponential transformation if the skew was greater than 0.5. An age-adjusted Pearson's correlation was utilized to assess bivariate relationships. Other methods used include Mann-Whitney-Wilcoxon test and Fisher's Exact test when appropriate to compare ischemic and non-stroke patients.

Results:
Adjustments for age were included due to weak to strong correlations with various measures of NLR and QIDS. There is a statistically significant correlation between the baseline NLR and baseline QIDS (correlation = -0.54, p-value=0.013) and QIDS at 30 days (correlation=-0.67, p-value=0.028). NLR at 24 hours has a statistically moderate correlation with QID at 30 days (correlation=0.39, p-value=0.055) and QIDS at 90 days (correlation=0.36, p-value=0.134).

Conclusions:
This preliminary study suggests that NLR at hospital admission could serve as a prognostic marker of post stroke depression at thirty days. Utilization of this marker in clinical practice for stroke care could identify high risk patients and result in earlier treatment of depression. Validation studies and preventative strategies will need to be explored in future studies.
Abstract TMP87: The Efficacy of a Chronic Care Based Intervention on Secondary Stroke Prevention Among Vulnerable Stroke Survivors: A Randomized, Controlled Trial
Authors: Cheng Eric M , Cunningham William E , Towfighi Amytis , Sanossian Nerses , Bryg Robert J , Anderson Thomas L , Barry Frances , Douglas Susan M , Hudson Lillie , Ayala-Rivera Monica , Guterman Jeffrey J , Gross-Schulman Sandra G , Beanes Sylvia , Jones Andrea S , Liu Honghu , Vickrey Barbara G
Published: July 2021

Background:
Effective interventions to improve stroke preventative care in vulnerable populations have not been reported.

Methods:
We tested the impact of a chronic care model-based intervention program among 407 subjects with a recent stroke or transient ischemic attack at four Los Angeles County public hospitals. All subjects had a baseline systolic blood pressure (SBP) of at least 120 mm Hg and were randomized after baseline assessment in a 1:1 ratio to usual care or intervention, stratified by hospital and by English/Spanish language. The care management intervention was led by bilingual nurse practitioners or physician assistants, and it consisted of group clinics, self-management support, report cards, decision support, and coordination of ongoing care. Intention-to-treat analyses were conducted using repeated-measures mixed-effects models. The primary outcome was change in SBP. Secondary outcomes were other measures of SBP, low-density lipoprotein (LDL), ACC/AHA 10-year cardiovascular risk, adherence to antihypertensive and to antithrombotic medications, and physical activity.

Results:
Mean age was 57 years, 60% were male, 18% were African-American race, and 69% were Hispanic ethnicity. 48% had not graduated from high school. Baseline SBP was 150 mm Hg in the usual care arm and 149 mm Hg in the intervention arm. 12 month data were obtained in 333 participants (82%). There were substantial declines in SBP in both the usual care and intervention arms (Table). However, there were no significant differences between the two arms in either improvement of SBP from baseline or other measures of stroke risk factor control. Subgroup analyses did not reveal a differential impact of the intervention by race/ethnicity.

Conclusion:
Our care management intervention did not improve stroke risk factor control beyond what was attained in usual care. Further analyses are ongoing, and those findings will be used to guide modification of the intervention for future testing.
Abstract TMP91: Phase I Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Oral Protease-activated Receptor-4 Antagonist BMS-986120
Authors: Ismat Fraz A , Ma Xuewen , Wang Zhaoqing , Frost Charles E , Ni Yan G , Yang Jing
Published: July 2021

Introduction:
BMS-986120 is a potent and selective oral antagonist of protease-activated receptor-4 (PAR4), a thrombin-activated platelet receptor thought to be important in thrombus propagation and pathological vascular occlusion. PAR4 antagonism has potential therapeutic utility in the treatment and prevention of thrombotic diseases. Preclinical arterial thrombosis models showed greater efficacy than current antithrombotics, including aspirin, clopidogrel and vorapaxar, with lower bleeding risk.

Hypothesis:
This report presents results from the initial Phase I randomized, double-blind, placebo-controlled single- and multiple-ascending oral dose studies of BMS-986120.

Methods:
To assess the pharmacokinetics (PK), pharmacodynamics (PD), safety profile and tolerability of BMS-986120, single doses of BMS-986120 from 0.5-180 mg were administered to 42 healthy subjects and multiple doses of 2.5-100 mg daily for up to 14 days to 24 subjects, randomized with placebo.

Results:
BMS-986120 PK showed rapid absorption and distribution with slow terminal elimination. Exposures increased in a dose related manner. BMS-986120 selectively inhibited PAR4 agonist peptide (PAR4-AP) induced ex-vivo platelet aggregation and p-selectin expression in a dose- and concentration-dependent manner. Complete inhibition of induced platelet aggregation for at least 24 hours was observed in all subjects with doses ≥10 mg daily. PAR1 platelet activation was unaffected. Treatment-emergent adverse events (AEs) were reported at a frequency similar to placebo. There were no drug-related discontinuations or bleeding-related clinical findings or AEs. Laboratory assessments, including routine coagulation tests and template bleeding times, showed no clinically relevant trends.

Conclusions:
BMS-986120 was safe and well tolerated by healthy subjects. These results represent the first reported clinical experience of a selective oral PAR4 antagonist.
Abstract TP125: Intracranial Stenosis Subtypes in Patients Aged 45 Years or Younger
Authors: Xu Wei-Hai , Xu Yu-Yuan , Li Ming-Li , Jin Zheng-Yu , Sun Zhao-Yong , Hou Bo , Zhou Hai-Long , Feng Feng , Gao Shan
Published: July 2021

Objective:
Using high-resolution magnetic resonance imaging(HRMRI), we sought to examine the proportions of intracranial stenosis subtypes and their clinical relevance in young patients(≤45 years old).

Methods:
One hundred and twenty-nine consecutive patients (mean age 36±8 years) with middle cerebral artery stenosis and without Moyamoya disease were evaluated by HRMRI. The stenosis was classified as eccentric stenosis, concentric stenosis, and mixed stenosis if both eccentric and concentric stenosis occurred in one vessel. The clinical data and vessel wall properties were analyzed among the subtypes.

Results:
Eccentric stenosis was found in 86 (69.4%) patients, while concentric stenosis was found in 26 patients (21.0%) and mixed stenosis in 12(9.7%) patients. The patients with eccentric stenosis were older (p<0.001) and more likely had atherosclerosis risk factors (p=0.024). The patients with concentric stenosis were more likely female, and aged 35 years old or younger. All mixed stenosis were high-grade (>70%) stenotic. All concentric stenosis showed constrictive remodeling, while eccentric and mixed stenosis had heterogeneous remodeling types. In 34 patients with available enhanced images, ring enhancement was revealed in 8/9(88.9%) concentric stenosis and 5/5(100%) mixed stenosis, but only in 3/20(15%) eccentric stenosis (P<0.001). Ten of twelve (83.3%) patients with mixed stenosis were symptomatic, more frequently than the patients with eccentric stenosis (57.0%, p=0.072) and the patients with concentric stenosis (50%, p=0.052).

Conclusions:
The distinct vessel wall features among intracranial stenosis subtypes suggest heterogeneous pathophysiology. Further studies are required to investigate whether mixed stenosis is the most vulnerable subtype in young patients (≤45 years old).
Abstract TP137: The Association Between MRI-detected Carotid Vulnerable Plaque and Coronary Artery Stenosis
Authors: Nagata Manabu , Yoshida Kazumichi , Yoshida Kazumichi , Fukumitsu Ryu , Takenobu Yohei , Kikuchi Takayuki , Ishii Akira , Takagi Yasushi , Miyamoto Susumu
Published: July 2021

It is now accepted that carotid artery stenosis should be treated as a part of systemic atherothrombosis. However, little is known about the association in atherosclerosis between the carotid and coronary arteries. We retrospectively investigated the association between carotid plaque vulnerability diagnosed on carotid magnetic resonance imaging (MRI) and coexisting coronary artery stenosis in patients scheduled for carotid endarterectomy (CEA) or carotid artery stenting (CAS).

Eighty-nine consecutive cases that underwent carotid reconstruction for carotid artery stenosis at Kyoto University Hospital between 2010 and 2015 were enrolled in this study. Ten cases that received neither coronary angiography (CAG) nor coronary computed tomography angiography (CCTA) as preoperative examinations, 6 cases with restenosis after CEA or CAS, and 2 cases that did not undergo carotid MRI were excluded. We evaluated relative overall signal intensity (roSI) of the carotid plaque on T1-weighted imaging and coronary artery stenosis detected on CAG or CCTA in the remaining 71 cases. Carotid plaques with roSI >1.5 were defined as MRI-detected vulnerable plaques.

Thirty-one cases had a history of previous coronary intervention (stenting or bypass surgery), of which 26 (84%) showed carotid vulnerable plaques. In the cases with no history of coronary intervention, coronary artery stenosis was newly detected in 21 cases, and was not demonstrated in the other 19 cases. Fifteen of the 21 cases with coronary artery stenosis (71%) also showed carotid vulnerable plaques. On the other hand, only 4 of the 19 cases without coronary artery stenosis (21%) had carotid vulnerable plaques, representing a significant difference (P<0.05).

Among the cases with no history of coronary intervention, prevalence of coronary artery stenosis in cases with carotid vulnerable plaques was 79%, significantly higher than that in cases without carotid vulnerable plaques (29%).

In conclusion, this study demonstrated that patients with carotid vulnerable plaques are more likely to have advanced coronary artery stenosis. Plaque characterization by carotid MRI is useful not only for treatment of carotid artery stenosis, but also for predicting coronary artery stenosis.