bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP38: Utilization Patterns and Outcomes of Stenting for Intracranial Atherosclerosis in the United States: 2010-2016
Authors: Saber Hamidreza , Saver Jeffrey L , Sheth Sunil A , Navi Babak , Rajah Gary , Jadhav Ashutosh P , Jahan Reza , Duckwiler Gary R , Liebeskind David S
Published: June 2021

Introduction:
Recent national utilization and in-hospital outcomes of stenting for intracranial atherosclerosis following emergent or elective hospitalizations are not well-established.

Methods:
Using validated codes, we identified all hospitalizations with stenting for intracranial atherosclerosis in the National Inpatient Sample (NIS) from 2010-2016. The primary outcome was in-hospital mortality. Poor outcome was defined as death or discharge to skilled nursing facility. We used multivariable models adjusting for relevant demographic, hospital and clinical variables to examine outcomes among hospitalizations with elective or non-elective procedures. We used NIS sampling weights to calculate utilization patterns and clinical outcomes across time.

Results:
A total of 4,733 eligible hospitalizations with intracranial stenting were identified during the study period (21% elective admissions). An abrupt decline in intracranial stenting was observed in the 3
rd
quarter of 2011 after publication of the SAMMPRIS trial. After 2011, there were steadily increasing rates of hyperacute intracranial stenting combined with mechanical thrombectomy whereas elective intracranial stenting trended downward. In-hospital mortality for non-elective stenting was unchanged across the study period, whereas in-hospital mortality for elective intracranial stenting declined significantly. In multivariable models, age (OR, 1.1), female sex (OR, 1.64) and concomitant thrombectomy (OR, 1.95) were associated with poor outcome in the non-elective stenting cohort, whereas black race (OR, 2.1) and atrial fibrillation (OR, 3.61) were independent predictors for poor outcome in the elective stenting cohort (all p < 0.05).

Conclusion:
Elective hospitalizations for intracranial stenting accounted for approximately one-fifth of all procedures for intracranial atherosclerosis in the U.S. and were associated with improving outcomes from 2010 to 2016.

Figure: Intracranial stenting utilization patterns for intracranial atherosclerosis in US (2010-2016).
Abstract WMP45: Borderzone Infarct Pattern Predicts Recurrent Stroke in Patients With Intracranial Stenosis
Authors: Prabhakaran Shyam , Sangha Rajbeer , Ansari Sameer , Romano Jose , Sylaja PN , Liebeskind David S
Published: June 2021

Introduction:
Despite aggressive medical management, patients with symptomatic intracranial atherosclerotic disease (ICAD) remain at high risk for recurrent stroke. There are no reliable biomarkers to identify those at highest risk and in whom flow restorative procedures may be warranted. We hypothesized that a borderzone infarct pattern would predict 90-day recurrent stroke in the territory of symptomatic ICAD.

Methods:
Using the prospective registry at a single center, we identified consecutive patients admitted between 2012 and 2017 with confirmed ischemic stroke or transient ischemic attack (TIA) and independently adjudicated symptomatic ICAD with stenosis of >50%. We ascertained clinical events within 3 months of index stroke through telephone interview. Ischemic stroke in the territory of the symptomatic stenotic artery was the primary outcome. A blinded rater assessed infarct pattern: single perforator, territorial, borderzone, or mixed. We evaluated whether infarct pattern was a predictor of recurrent stroke using logistic regression adjusting for age, sex, prior stroke, initial NIHSS score, location of stenosis, degree of stenosis, and use of dual antiplatelet therapy at discharge.

Results:
Among 212 patients who met study criteria, the mean age was 68.2 (±12.2) years and median initial NIHSS score was 3 (interquartile range 1-6). Symptomatic ICAD was localized to the anterior circulation in 132 (64.2%) patients and 171 (80.7%) had stenosis >70%. Isolated borderzone infarcts were noted in 18 patients (8.5%) while they were present in 34 (16.0%) other patients with mixed pattern. At 3 months, 51 (24.1%) patients experienced recurrent stroke in the territory. Among patients with any borderzone infarct, 20 (38.7%) had recurrent stroke versus 31 (19.4%) in patients with other patterns (p=0.005). In adjusted analysis, presence of any borderzone infarct was independently associated with recurrent stroke (aOR 2.59, 95% CI 1.23-5.48, p=0.012).

Conclusions:
In a single-center observational cohort study, we found that a borderzone infarct pattern was a strong predictor of recurrent stroke at 3 months in patients with symptomatic ICAD. Our data suggest that hypoperfusion may be an important mechanism of recurrent stroke in this population.
Abstract WMP47: Poor Risk Factor Control and Lower Levels of Physical Activity Predict Incident Major Cardiovascular Events in Patients With Symptomatic Vertebrobasilar Disease: A Post-Hoc Analysis of the SAMMPRIS Trial
Authors: Croll Leah , Chang Andrew , Scher Erica , Ishida Koto , Torres Jose , Riina Howard , Frontera Jennifer , Lord Aaron , Yaghi Shadi
Published: June 2021

Background:
Symptomatic vertebrobasilar (VB) atherosclerotic disease is associated with a high risk of recurrent stroke despite optimal medical therapy.

Objective:
In this study, we aim to examine the prognosis and associations between risk factors and recurrent major cardiovascular events (MACE) in patients with symptomatic VB stenosis randomized in the medical arm of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study.

Methods:
Data from subjects in the medical arm of the SAMMPRIS trial with an infarct in the territory of vertebral or basilar arteries (n= 73) were analyzed. The primary outcome was MACE: defined as stroke, myocardial infarction, or other cardiovascular death during follow up. Mean risk factor values were compared between subjects who met the primary outcome at 2 years versus those who did not, using T-tests and χ2 tests.

Results:
Among 73 patients with VB stenosis randomized to medical treatment, 18 patients (24.6%) had recurrent MACE over a mean follow up of 2.8 years. This was significantly less than the rate of MACE in those with VB enrolled in the WASID trial (9.7 per 100-patient years vs. 20.9 per 100-patient years, p<0.01). Predictors of MACE at 2 years were increased triglyceride level (adjusted OR per 50 units increase in triglyceride 1.94, 95% CI 1.15-3.28) and increased HbA1c level (adjusted OR per 1 unit increase in HbA1c 2.07, 95% CI 0.97-4.45), and lower physical activity status measured by PACE (out of target defined by PACE ≤ 4: moderate activity < 5 days per week or intense activity < 3 days per week) (2.5 ± 1.0 vs. 3.3 ± 1.8, p = 0.028) (Table).

Conclusions:
In patients with symptomatic VB disease, improvement of medical treatment over time led to a reduction in cardiovascular event rates but this risk remains elevated as nearly 1 in 5 patients had MACE within 2 years. Further risk factor optimization and lifestyle changes are needed to reduce the rates of MACE in this patient population.
Abstract WMP48: 3D MR Vessel Wall Imaging Reveals Plaque-Specific Responses to Medical Therapy in Patients With Symptomatic Intracranial Atherosclerotic Disease: Initial Experience
Authors: Xiao Jiayu , Miao Huijuan , Shlee Song , Schlick Konrad , Jiang Tao , Xia Shuang , Han Tong , Maya Marcel , Lyden Patrick , Li Debiao , Guo Xiuhai , Yang Qi , Fan Zhaoyang
Published: June 2021

Introduction:
Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke worldwide and carries a high rate of recurrence. Follow-up of symptomatic ICAD routinely relies on assessment of lumen stenosis. Magnetic resonance vessel wall imaging (MR-VWI) has recently demonstrated the potential to reliably quantify plaque features. This work presents our experience in using serial MR-VWI to quantify the morphological changes of culprit lesions in response to medical therapy in patients with symptomatic ICAD.

Methods:
Twenty-four patients (4 females; age 46.75±14.05 years) with acute ischemic stroke secondary to ICAD underwent baseline (1-44 days after onset) and follow-up (3-15 months after baseline) 3D whole-brain MR-VWI, which was used to acquire pre- and post-contrast images. Quantitative plaque features, including plaque volume, peak normalized wall index (pNWI), maximum wall thickness, stenosis degree, pre-contrast plaque-wall contrast ratio (CR), and post-contrast plaque enhancement ratio (ER), were derived from both baseline and follow-up MR-VWI scans. Patients with 18-month clinical follow-up were divided into progression and non-progression groups depending on whether major vascular events (stroke, TIA, death) occurred.

Results:
Seventeen patients were categorized into the non-progression group and 4 into the progression group. Maximum wall thickness (P=0.047), CR (P=0.020) and ER (P=0.012) showed significant decreases in the non-progression group. In the progression group, all 4 patients showed an increase in pNWI, stenosis degree and CR; plaque volume, maximum wall thickness and ER increased in three patients. Typical cases are shown in Figure.

Conclusions:
Quantitative assessment of lesion-specific responses to medical therapy is clinically feasible with serial MR-VWI. The changes of plaque over time may be useful for ischemic stroke risk stratification with implications for ICAD medical management.
Abstract WMP49: Disparities in Rising Incidence of Stroke in Adults Younger Than 65
Authors: Jones Erica , Chu Kristie , Sharrief Anjail , Savitz Sean , Vahidy Farhaan
Published: June 2021

Introduction:
Increased incidence of stroke in young adults has been attributed to rising prevalence of known stroke risk factors such as hypertension. Our aim is to identify young adult demographic groups most in need of clinical and public health intervention to prevent future increases in stroke incidence.

Methods:
We performed retrospective analyses on hospitalization data from the National Inpatient Sample (NIS) in adults aged 18- 64 years with diagnosis of ischemic stroke, hemorrhagic stroke, or subarachnoid hemorrhage from 2006 to 2015 and compared hospitalization rates over two-year periods.

Results:
We included data from 1,750,081 hospitalizations meeting inclusion criteria. Comparing 2006-07 to 2014-15, rates of hospitalization for stroke increased significantly across all analyzed gender and racial groups except Asian/Pacific Islanders aged 18-34 and 34-45. Non-Hispanic Blacks (NHB) had the highest stroke hospitalization rates in those aged 18-44, and Asian/Pacific Islander rates were highest in ages 45-64 (Figure 1d,f). In this period, there was a 26% overall increase in risk of hospitalization for stroke in young adults with 42% (CI 1.28 - 1.57) increased risk in women aged 18-34 and 41% (1.32 -1.51) in men aged 35-44. Regionally, the South had the highest incidence of stroke hospitalization in all age groups but the highest increase in risk over the decade was seen in the Northeast. Prevalence of hypertension among hospitalized patients remained unchanged or decreased while prevalence of all other risk factors increased, mostly in obesity and lipid disorders (Figure 1h).

Conclusions:
Despite public awareness, stroke incidence continues to increase in young patients remaining highest among minorities and in the Southern states, but rising more in the Northeast. Personalized approaches and geographic aspects, in addition to vascular risk factor control, will all likely be needed to reduce stroke risk in these different patient populations.
Abstract WMP54: Estimates of the U.S. Burden of Pregnancy-Associated Stroke Attributable to Common Vascular Risk Factors
Authors: Chatterjee Abhinaba , Parikh Neal S , Navi Babak B , Kamel Hooman
Published: June 2021

Background:
The incidence of pregnancy-associated stroke may be increasing. The degree to which this increase is associated with increases in common stroke risk factors is uncertain.

Methods:
We used the National Inpatient Sample (NIS) and National Health and Nutrition Examination Survey (NHANES) to estimate the change between 1999 through 2014 in the prevalence of common stroke risk factors among women 12-45 years of age. These risk factors were hypertensive disorders of pregnancy (gestational hypertension, preeclampsia, or eclampsia), which was ascertained using NIS, and diabetes mellitus, obesity, and smoking, which were ascertained using NHANES. We extracted previously published relative risk estimates for the association between each risk factor and ischemic stroke in pregnant women. Using these estimates, we calculated the attributable risk and expected number of ischemic strokes among pregnant women with each risk factor. We used the NIS to estimate the trend in ischemic strokes documented during a hospitalization for labor and delivery, and modeled trends in such strokes attributable to changes in the prevalence of each stroke risk factor over time.

Results:
The rate of ischemic stroke increased from 7.7 (95% CI, 5.0-10.5) per 100,000 deliveries in 1999-2000 to 12.7 (95% CI, 9.5-15.9) per 100,000 deliveries in 2013-2014 (Fig). Based on changes in the prevalence of hypertensive disorders of pregnancy, diabetes, obesity, and smoking between 1999 and 2014, the expected increase in pregnancy-associated stroke attributable to these risk factors would be approximately 10%, in contrast to the nearly 65% relative increase in strokes documented during pregnancy hospitalizations during this period.

Conclusions:
Changes in the prevalence of common stroke risk factors explain a small fraction of the apparent increase in pregnancy-associated stroke in the U.S. during the past 2 decades.
Abstract WMP56: Association of Mean Platelet Volume and Its Genetic Variants With Stroke Severity and One-year Mortality in a Polish Stroke Cohort
Authors: Miller Malgorzata , Henninger Nils , Slowik Agnieszka
Published: June 2021

Background:
Increased mean platelet volume (MPV) is a marker of worse outcomes in cardiovascular disorders, however its prognostic role in patents with ischemic stroke and possible genetic underpinnings remains uncertain. We aimed to determine whether MPV and selected single nucleotide polymorphisms (SNPs) that have been associated with MPV in genome-wide association studies (GWAS) relate to stroke severity, functional outcome on discharge, and one-year mortality in patients with ischemic stroke.

Methods:
We retrospectively analyzed 577 patients with first ever ischemic stroke. Genotyping of 3 SNPs (rs342293, rs1354034, rs7961894) was performed using a real-time polymerase chain reaction allelic discrimination assay. Multivariable regression was used to determine the association of MPV and MPV-associated SNPs with the National Institutes of Health Stroke Scale (NIHSS) score on admission, modified Rankin Scale (mRS) on discharge, and data on one-year mortality.

Results:
Rs7961894, but not rs342293 and rs1354034 SNP, was independently associated with MPV in the highest quartile (MPV Q4). MPV Q4 was associated with significantly greater admission NIHSS (p=0.004), poor discharge outcome (p=0.034), and worse one-year mortality (p=0.033). After adjustment for pertinent covariates, MPV Q4 remained independently associated with a greater admission NIHSS score (p=0.025). Patients carrying T>C variant of rs7961894 SNP had a significantly lower one-year mortality as compared to patients with CC genotype (p=0.029; Log-Rank test; Fig.1) and T>C variant of rs7961894 SNP remained an independent marker of a lower one-year mortality (HR=0.30; 95%CI:0.13-0.70; p=0.006) in the studied population.

Conclusion:
MPV is a marker of stroke severity and rs7961894 is independently associated with MPV in acute phase of ischemic stroke and relates to one-year mortality after stroke.
Abstract WMP59: White Matter Hyperintensities Play a Pivotal Role in Progression of Cerebral Small Vessel Disease: A 7-Year Chinese Urban Community Study
Authors: Xia Yiwei , Shen Yi , Wang Yi , Yang Lumeng , Wang Yiqing , Li Yu , Liang Xiaoniu , Zhao Qianhua , Wu Jianjun , Chu Shuguang , Liang Zonghui , Wang Xiaoxiao , Qiu Bensheng , Ding Ding , Ding Hansheng , Cheng Xin , Dong Qiang
Published: June 2021

Objective:
To explore the role of WMH in progression of CSVD in an urban community in China over a period of 7 years, and to investigate associations between WMH volume (baseline & progression) and cognitive impairment.

Methods:
CSVD markers and neuropsychological tests at baseline and follow-up of 191 participants of the Shanghai Aging Study (SAS) were assessed. WMH volume were assessed by automatic segmentation based on U-net model. Lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (ePVS) were rated manually. SVD score was rated as the total burden of CSVD markers. We performed multivariate linear regression and binominal logistic regression. We plotted progression of markers by baseline WMH volume in tertile.

Results:
Participants with higher baseline WMH volume developed more progression of WMH volume, increased risk of incident lacunes, incident CMBs, and ePVS progression. Mean change of WMH volume over 7 years was 4.27mL (0.62mL/y) for all participants, 3.21mL for participants with 1st tertile WMH volume at baseline, 4.19mL for those with 2nd tertile WMH, and 5.43mL for those with 3rd tertile WMH. Incident lacunes and incident CMBs were predominantly seen in participants with 2nd and 3rd tertile WMH. WMH (baseline & progression) were associated with decline of executive function.

Conclusions:
WMH play a pivotal role in progression of cerebral small vessel disease and are associated with decline of executive function in a Chinese urban community study over a period of 7 years.
Abstract WMP6: Stenting Placement During Endovascular Treatment in VBAO Was Not Associated With 90-Day Outcome in the Basilar Artery Occlusion Endovascular Intervention versus Standard Medical Treatment (BEST) Trial
Authors: Dai Qiliang , Xu Gelin , Liu Xinfeng , Nogueira Raul
Published: June 2021

Background:
The impact of intracranial stenting placement during endovascular treatment for acute vertebrobasilar artery occlusion (VBAO) remains elusive. We aim to investigate the influence of intracranial stenting on 90-day outcomes in the BEST trial.

Methods:
All patients who underwent endovascular treatment in BEST trial were included in the analysis. The primary efficacy and safety outcome measures were the 90-day rate of favorable outcome (mRS 0-3) and mortality, respectively. Logistic regression was used to investigate the association between stenting placement and outcome.

Results:
All 77 patients who received endovascular treatment in the trial were included (e.g. full As-Treated population). Baseline and procedural characteristics are summarized in
Table 1
. Stenting was performed in 26% (20/77) of the patients. Favorable outcome was achieved in 46.8% patients and mortality rate was 29.9%. Multivariable logistic regression showed that stenting placement in VBAO was not a predictor of either 90-day favorable outcome (adjusted OR, 0.91; 95% CI, 0.31 to 2.65, p=0.86) or 90-day mortality (adjusted OR, 0.91; 95% CI, 0.28 to 3.00, p=0.88).

Conclusion:
Stenting placement in VBAO during endovascular treatment did not impact outcomes in the BEST trial. Our data suggest that stent placement is a reasonable option for selected VBAO patients.

Table 1: Baseline Characteristics and Outcomes Measures in as-treated population.
Abstract WMP63: The Yield of Inpatient Cardiac Telemetry in Ischemic Stroke Patients With Ipsilateral Large Artery Stenosis
Authors: Delamerced Amador , Boyanpally Anusha , El Jamal Sleiman , Burton Tina , Cutting Shawna , Stretz Christoph , Sacchetti Daniel , Reznik Michael , Mahta Ali , Madsen Tracy , Yaghi Shadi , Furie Karen , Mac Grory Brian C
Published: June 2021

Introduction:
The detection of atrial fibrillation (AF) is a crucial component of ischemic stroke secondary prevention. Inpatient cardiac telemetry is part of the structured inpatient workup for ischemic stroke but the yield of telemetry is unknown when ipsilateral, hemodynamically-significant large artery atherosclerosis is identified at the time of initial presentation.

Methods:
We performed a single-center, retrospective, cohort study utilizing data from an institutional quality improvement database. We identified consecutive patients with acute ischemic stroke presenting between July 2015 and September 2017. We included patients with hemodynamically-significant (>50%) large artery stenosis in the arterial territory subserving the region of infarct. We excluded patients with a known history of AF. We determined the yield of an electrocardiogram, inpatient telemetry and outpatient cardiac event monitoring in detecting new AF. Groups with and without AF were compared using unpaired student’s T-test for continuous variables and Chi
2
test for categorical variables.

Results:
We identified 1435 patients presenting to our institution during the study period of whom 209 (14.6%) met inclusion criteria. Patients were aged 69.37±12.6 years and 33% were female. Of these patients, 19 (9.1%) were found to have new AF during their hospitalization and a further 2 (1%) were found to have AF on extended cardiac monitoring. Thirty seven patients had 30-day cardiac monitoring performed after hospitalization and the yield on this was 5.4% for the detection of AF. Patients with AF were older (76.29±11.31 years vs. 68.60±12.58 years, p=0.008) and had higher rates of hypertension (94% vs. 75%, p=0.04) and hyperlipidemia (72% vs. 52%, p=0.09). In all patients, anticoagulation was planned after the discovery of AF.

Discussion:
Inpatient cardiac telemetry detects new atrial fibrillation in 9.1% of patients known to have hemodynamically-significant large artery disease at the time of initial presentation. The yield of further outpatient cardiac monitoring is lower (5%). This hypothesis-generating study is limited by its retrospective nature and the potential for selection bias.
Abstract WMP66: Left Atrial Appendage Flow Velocity is Associated With Ischemic Events and Brain Infarcts in Atrial Fibrillation
Authors: Ignacio Gian C , Chang Andrew D , Panda Nikhil C , Chu Antony , Wu Michael , Cutting Shawna M , MacGrory Brian C , Burton Tina M , Poppas Athena , Furie Karen L , Song Christopher , Jayaraman Mahesh V , Atalay Michael K , Yaghi Shadi
Published: June 2021

Objective:
Clinical predictors of ischemic stroke in the setting of atrial fibrillation (AF) have been identified, but there is limited data on predictors in the context of abnormal flow originating from the left atrial appendage. We hypothesize that reduced LAA flow velocity is associated with cerebrovascular ischemic events in patients with AF.

Methods:
We investigated consecutive patients with AF evaluated for ablation. Peak flow velocities at the orifice of the left atrial appendage (LAA) were obtained by transeosphageal echocardiography (TEE) studies, and elevated velocities were defined as greater than 40 cm/sec, in line with prior studies. The primary outcome was defined as the presence of any of the following: history of stroke/transient ischemic event, or non-lacunar brain infarct on brain imaging performed before the TEE. Univariate and multivariable analyses were performed to determine the association between LAA peak flow and the primary outcome, adjusting for CHADS2Vasc score.

Results:
We identified 322 patients with TEE performed. The mean age was 62.1 years and 24.5% men. Patients with LAA-flow velocity < 40 cm/sec were more likely to have the primary outcome (10.7% vs 4.3%, p=0.023). This association persisted after adjusting for CHADS2VASc (OR, 2.62; 95% CI, 1.09-6.33, p = 0.032).

Conclusion:
Low velocity in the LAA is associated with cerebrovascular ischemic events in patients with AF. More studies are needed to deterine whether LAA flow velocity can help risk stratify “low risk” patients with AF.
Abstract WMP68: The MicroRNA Expression Analysis for Thrombus From Acute Ischemic Stroke
Authors: Kim Jeong Min
Published: June 2021

Background:
The thrombus retrieved from mechanical thrombectomy among stroke patients could provide important information regarding stroke mechanism and its prognosis. We investigated microRNA expression pattern from thrombus to differentiate stroke mechanism.

Methods:
Between September 2016 and March 2019, acute ischemic stroke patients who received intra-arterial mechanical thrombectomy from Chung-Ang University Hospital, Seoul, Korea were eligible to be included. After obtaining informed consent, the thrombus was stored at -70°C nitrogen tank. First, we performed microRNA microarray analysis for the patients with clearly identified stroke mechanisms including large artery atherosclerosis, cardioembolism with atrial fibrillation and cardioembolism with valvular heart disease. Second, those microRNAs derive from microarray analysis were validated by quantitative real time polymerase chain reaction, and correlation analyses were performed between microRNA levels and clinical data. Finally, the expression levels of microRNAs were compared between the patients with early neurological deterioration (END) after stroke and those without.

Results:
A total of 48 thrombi had been retrieved from 51 patients. The microarray analysis of microRNA revealed that 42 microRNAs were significantly altered among the three groups out of 869 examined microRNAs. Ejection fractions were negatively correlated with miR-450b-5p levels (r=-0.448, p<0.0001) and e/e’ were positively correlated with miR-378f (r=0.640, p<0.001). The patients with END exhibited higher levels of miR-93-5p and lower levels of miR-629-5p.

Conclusion:
The microRNA expression pattern can provide information regarding stroke mechanisms, underlying heart dysfunction and prognosis after recanalization treatment.
Abstract WMP69: Profiling Extracellular Vesicle Surface Markers as Diagnostic Tool in Patients With Transient Ischemic Attack (TIA)
Authors: Bianco Giovanni , Burrello Jacopo , Manno Concetta , Nannoni Stefania , Michel Patrik , Bolis Sara , Vassalli Giuseppe , Albers Gregory W , Cianfoni Alessandro , Barile Lucio , Cereda Carlo W
Published: June 2021

Introduction:
-TIA diagnosis is challenge. A circulating blood-based biomarker, supporting clinical and imaging evaluation, would be fundamental for optimizing the diagnosis of true brain ischemic events. Surface proteins carried by cellular secreted extracellular vesicles (EV), reflect abnormal inflammation and coagulation. We aimed to test the performance of EV surface proteins in discriminating true ischemic TIA.

Methods:
- We analyzed n=40 patients with suspicion of TIA, and n=20 asymptomatic matched controls. According to the PREDISC score, which includes clinical and imaging (multimodal MRI) criteria, patients were stratified as “unlikely” (score 0-1, n=10), “possibly” (score 2-3, n=15), or “very likely” (score 4-8, n=15) of having true ischemic TIA. Serum-derived EV were quantified by nanoparticle tracking analysis and EV-surface profile characterized by flow cytometry assay. Linear discriminant analysis (LDA) and random forest (RF) were built and validated through supervised machine learning algorithms.

Results:
- The concentration of circulating serum-derived EV was significantly increased in patients with proven ischemic events ranging in PREDISC score of 4-8 (p<0.001) and for those classified as “possibly” (score 2-3, P<0.05) as compared to controls. No significant differences were observed in patients stratified as “unlikely” versus controls. Overall EV concentration was directly correlated with the PREDISC score (R = 0.712; P < 0.001). Among EV-surface markers, CD8, CD2, CD62P, MCSP, CD42a, CD44, CD326, CD142, CD31, and CD14 were identified as discriminants between groups (p<0.05). Their expression was correlated with the PREDISC score (R range 0.320-0.461; P < 0.05), and associated with the occurrence of true ischemic TIA, as confirmed by univariate analysis (p<0.05). We combined 37 differentially expressed EV antigens in two models to predict PREDISC and achieved an accuracy of 95.0% and 90.0%, for the LDA and the RF model respectively.

Conclusion:
- Patients with recent true ischemic TIA appear to have a different cellular secreted EV profile in blood compared to controls. EV profile measurement is a promising novel biomarker to be validated in future studies addressing the optimization of TIA diagnosis.
Abstract WMP73: TGFβ-Activated Kinase 1 (TAK1) is a Key Molecular Switch That Drives Proinflammatory Microglia/macrophage Responses and Aggravates Long-Term Stroke Outcomes
Authors: Wang Rongrong , Pu Hongjian , Ye Qing , Jiang Ming , Chen Jun , Shi Yejie
Published: June 2021

Introduction:
Microglia/macrophages (Mi/MΦ) profoundly influence stroke outcomes, but the molecular mechanisms dictating their functional phenotype after brain ischemia/reperfusion (I/R) are poorly understood. We hypothesized that activation of TAK1, a key MAPKKK upstream of multiple inflammation-regulating pathways, drives Mi/MΦ towards a proinflammatory phenotype and potentiates I/R brain injury.

Methods:
TAK1 was targeted in mice by tamoxifen-induced, Mi/MΦ-specific knockout (mKO) or a relatively selective inhibitor 5Z-7-oxozeaenol (OZ; 2.5 mg/kg i.p.). Sensorimotor/cognitive deficits, grey/white matter injury and brain inflammatory profiles were assessed after 1 h MCAO and reperfusion.

Results:
TAK1 mKO markedly ameliorated neurological deficits in the rotarod, cylinder and water maze tests (p<0.05 vs WT, n=10-11/group) for at least 35 d after I/R. Mechanistically, RNA-seq (n=3/group) of FACS-sorted brain Mi (CD45
low
) and MΦ (CD45
high
) cells revealed that multiple genes participating in pro-inflammatory responses were downregulated in both Mi and MΦ from mKO mice versus WT mice 3 d after I/R. Consistent with the phenotype of mKO, OZ mitigated neuroinflammation 3 d after I/R, reflected by less Iba1
+
/CD16
+
proinflammatory Mi/MΦ and less brain invasion of peripheral immune cells (neutrophils, MΦ, T cells). OZ treatment beginning 2 h after I/R effectively improved long term (35 d) sensorimotor and cognitive functions in the foot fault, rotarod and water maze tests (p<0.05 vs vehicle) in male (n=13-19/group) and ovariectomized female (n=11/group) mice. Furthermore, OZ promoted both gray matter (MAP2/NeuN staining) and white matter (Caspr/Nav1.6 staining) integrity at 35 d after I/R (p<0.05 vs vehicle, n=8/group).

Conclusions:
TAK1 promotes I/R-induced inflammation, brain injury, and maladaptive behavior by enhancing neurotoxic Mi/MΦ responses. TAK1 inhibition is a promising therapy to improve long term stroke outcomes in both sexes.
Abstract WMP79: Recapitulation on the Ground of Helicopter Flight Low Frequency Vibration Enhances Stroke Thrombolysis
Authors: Dhanesha Nirav , Schnell Thomas , Rahmatalla Salam , DeShaw Jonathan , Thedens Daniel , Parker Bradley , Zimmerman M. Bridget , Pieper Andrew A , Chauhan Anil K , Leira Enrique C
Published: June 2021

Background:
Understanding the potential effects on stroke outcome of the unique physical factors present in a helicopter ambulance flight is critical in the era of thrombectomy. However, this factor in patient care has not been adequately investigated.

Methods:
This was a prospective randomized blinded end-point animal study. A murine model of middle cerebral artery autologous thromboembolic occlusion (eMCAO) with rtPA reperfusion was exposed to three different settings: 1) a standardized actual helicopter flight, 2) a motion platform simulator that delivered the exact LFV signature of the helicopter, and 3) a ground control. Outcome measures included infarct size and BBB permeability on MRI, and neurological scores.

Results:
A total of 106 mice were analyzed. Within the rtPA group, LFV simulator mice displayed lower infarction volumes on MRI (31.6 vs. 54.9 mm
3
, p=0.007) and improved neurological scores (87 vs. 28%, p=0.0001) compared to ground control mice. By contrast, mice receiving saline did not show change in either infarction volume (80.9 vs. 95.3, p=0.8) or neurological scores (37 vs. 28%, p=0.7). No differences were seen in the actual helicopter flight group as compared with ground control. No treatment group showed any difference in permeability of the blood brain barrier, assessed by MRI.

Conclusion:
We found a synergistic beneficial effect of combining helicopter-like LFV and rtPA, which could provide a novel, safe, and potentially more efficacious intervention for patients with stroke. These results also suggest that non-LFV helicopter physical factors, such, as hypobaric environment, accelerations and noise, may have a negating effect on the otherwise positive effect of helicopter vibration on stroke outcomes. If so, strategies to minimize these negating factors might be expected to improve patient outcome.
Abstract WMP84: Effects of a New Thrombolytic Compound DC007d in Acute Brain Tissue Damage After Focal Embolic Stroke in Rats
Authors: Jiang Yinghua , Liu Ning , Wang Xiao-ying , Zhou Iris Yuwen , Chen Chienhsi , Yeh Mimi , Sun Philip Zhe
Published: June 2021

Background and Purpose:
DC007D is a novel small molecule designed to have thrombolytic and free radical scavenging activities. In this study, we aimed to test the potential neuroprotective effects of DC007D in embolic clot model of focal ischemic stroke in rats.

Methods:
All animals received intravenous infusion of either saline, 10 mg/kg DC007D or 10 mg/kg tPA at each experimental time point (1.5, 3 and 4.5 hrs after stroke, respectively). In first set of experiments, animals were treated at 1.5-hr after stroke. We performed a time course of multi-parametric MRI analysis including perfusion, diffusion and T2 relaxation. Brain infarction size and swelling rate were measured by TTC staining at 24 hrs after stroke. Next, in 3- and 4.5-hrs treatment experiments, we examined acute brain infarct volume, brain swelling rate, hemorrhagic transformation, neurological deficits. Additionally, we also tested potentially direct neuroprotection effects of DC007D in a mechanical filament pMCAO rat model. Lastly, the effect of DC007D in tPA activity in vitro, INR, and serum levels of tPA and PAI-1 activities in vivo at 24 hrs after stroke were assessed and compared.

Results:
Both tPA and DC007D treated at 1.5 hrs after stroke reduced hypoperfused area, diffusion, T2 lesion size and TTC-stained infarction. When treated at 3 hrs after stroke, DC007D had significantly better therapeutic effects in reducing brain infarction size, swelling rate and hemorrhagic transformation compared to conventional tPA treatment group. When treated at 4.5 hrs after stroke, both tPA and DC007D had no effects in brain infarction. However, tPA, but not DC007D, significantly increased brain swelling and intracerebral hemorrhagic transformation compared to saline controls. Our experimental results also showed that DC007D failed to have direct neuroprotection in the mechanical pMCAO rat model. Lastly, DC007D did not interfere tPA activity in vitro, and also did not significantly alter INR, serum levels of tPA and PAI-1 activities post stroke in vivo.

Conclusions:
DC007D is neuroprotective to embolic focal stroke of rats, likely via tPA/PAI-1 activity independent thrombolytic mechanism. It might be developed as a new and novel thrombolytics or adjunct for tPA thrombolytic reperfusion therapy.
Abstract WMP85: Simulation Training Improves Door-to-Needle Time for Intravenous Thrombolysis
Authors: Mikulik Robert , Svobodová Veronika , Pokorná Hana
Published: June 2021

Background:
Clinical need exists to shorten door-to-needle time (DNT) for intravenous thrombolysis but effective training methods are missing. Simulation training improves teamwork and logistics in numerous fields but it is not clear if simulation improves logistics in stroke.

Methodology
This is a nation-wide study to evaluate efficacy of simulation training conducted between 2016-2018 and measured by DNT in centers participating in simulation training program as compared to the rest of stroke centers in the Czech Republic. Information about DNT was obtained from prospectively collected data from nationally used Safe Implementation Treatment in Stroke Registry (SITS). Outcome is improvement in DNT in 2018 as compared to 2015 (after and before the simulation training period). Scenarios are based on real clinical cases and are initiated by pre-notification from EMS through indication of thrombolysis and ends by indication for mechanical thrombectomy. Simulation courses were conducted in standardly equipped simulation center (hospital bed, stretcher, simulation monitor, artificial CT scanner, audiovisual equipment etc.).

Results:
Between 2016 and 2018, 10 courses were conducted for stroke teams from 9 of all 45-stroke centers in the Czech Republic. DNT was available both in 2015 and 2018 in 41 (91%) of 45 stroke centers. Stroke centers that passed simulation training improved their DNT in 2018 as compared to 2015 by 30 minutes (95%CI 25.7-34.7) as compared to 20 minutes (95%CI 15.8-24.3) in stroke centers that did not pass the simulation training (p=0.01).

Conclusion:
DNT considerably shortened in all stroke centers and simulation training additionally improved door-to-needle time by 10 minutes. Simulation training is useful training method to improve logistics in stroke.
Abstract WMP91: Head CT at Emergency Department Treat-and-Release Visit for Headache is Associated With Increased Risk of Subsequent Hospitalization for Cerebrovascular Disease
Authors: Liberman Ava L , Wang Cuiling , Esenwa Charles , Cheng Natalie , Nisar Taha , Rahimian David , Antoniello Daniel , Erbfarb Amichai , Labovitz Daniel , Prabhakaran Shyam , Lipton Richard
Published: June 2021

Background:
Headache is a common presenting symptom among patients with misdiagnosed cerebrovascular (CVD) disease. Recent studies report that the occurrence of a head CT (HCT) during emergency department (ED) visit for non-specific neurological symptoms, such as vertigo, is associated with increased risk of stroke after ED discharge. We sought to evaluate whether the occurrence of HCT at ED visit for headache is associated with increased CVD risk.

Hypothesis:
Patients with headache complaints who have a HCT performed in the ED (exposed) are more likely to have a CVD admission within 365 days of ED discharge than those who do not receive a HCT (unexposed).

Methods:
We conducted a retrospective study of consecutive adult patients with headache complaints discharged to home (treat-and-release visit) from all four of the EDs affiliated with a single academic institution. Patients with headache complaints were defined as those with primary ICD-9/10-CM discharge diagnosis of benign headache; patients were included in our study at their first ED treat-and-release visit from 2013 to 2018. Subsequent CVD hospitalizations were identified using ICD-9/10-CM inpatient discharge codes and confirmed via chart review. We matched exposed to unexposed patients in a one-to-one fashion using propensity score methods. Standard descriptive statistics and relative risk (RR) with 95% CIs are reported.

Results:
Among 28,121 patients with an ED treat-and-release visit for headache complaints, 45.6% (n=12,812) underwent HCT during ED visit. A total of 0.4% (n=112) patients had a subsequent CVD admission within 365 days of ED visit. Using propensity score matching, 80.3% (n=10,295) of patients with HCT (exposed) were able to be matched. In the matched sample, exposed patients had a nearly two-fold increased relative risk of CVD at 365 days (RR: 1.83; 95% CI: 1.12-3.01). In secondary analysis, CVD risk at 180 days was also higher in exposed (RR: 2.06; 95% CI: 1.13-3.74).

Conclusion:
Having a HCT performed at index ED treat-and-release visit among those with headache complaints establishes a clinically meaningful risk gradient for subsequent CVD hospitalization. Some ED patients given a headache diagnosis may have been misdiagnosed at index visit.
Abstract WP106: Redefined Measure of Early Neurological Improvement Shows Treatment Benefit of Intravenous Tissue Plasminogen Activator Treatment in NINDS Rt-PA Acute Stroke Trial at 24 Hours
Authors: Agarwal Shashank , Scher Erica , Lord Aaron , Frontera Jennifer , Ishida Koto , Torres Jose , Rostanski Sara , Mistry Eva , Mac Grory Brian C , Cutting Shawna , Burton Tina , Silver Brian , Liberman Ava L , Mackenzie Mackenzie P , Furie Karen , Grotta James , Khatri Pooja , Saver Jeffrey L , Yaghi Shadi
Published: June 2021

Background and Purpose:
The first of the 2 NINDS Stroke Study trials did not show a significant increase in early neurological improvement (ENI), defined as NIHSS improvement by ≥ 4, with alteplase treatment. We hypothesized that ENI defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours.

Methods:
We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as [(admission NIHSS score–24-hour NIHSS score)x100/admission NIHSS score] and delta NIHSS as (admission NIHSS score–24-hour NIHSS score). We compared ENI using these definitions between alteplase vs. placebo patients. We also used receiver operating characteristic (ROC) curve to determine the predictive association of ENI with excellent 3-month functional outcomes [Barthel Index (BI) score 95 – 100 and modified Rankin scale (mRS) 0-1], good 3-month functional outcome (mRS 0-2) and 3-month infarct volume.

Results:
There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared to the placebo group (28% vs. 15%, p = 0.045) but not median delta NIHSS (3 vs. 2, p = 0.471). ROC curve comparison showed that percent change NIHSS (ROC
percent
) was better than delta NIHSS (ROC
delta
) and admission NIHSS (ROC
admission
) with regards to excellent 3-month BI (ROC
percent
0.83, ROC
delta
0.76, ROS
admission
0.75), excellent 3-month mRS (ROC
percent
0.83, ROC
delta
0.74, ROS
admission
0.78), and good 3-month mRS (ROC
percent
0.83, ROC
delta
0.76, ROS
admission
0.78). Percentage change had a stronger association with 90-day infarct volume than delta NIHSS score and both delta NIHSS and percent change in NIHSS were more pronounced with faster treatment times.

Conclusion:
In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.
Abstract WP109: Redefining Early Neurological Improvement After Intravenous Tissue Plasminogen Activator Treatment of Stroke
Authors: Agarwal Shashank , Cutting Shawna , Mac Grory Brian , Burton Tina , Jayaraman Mahesh , McTaggart Ryan , Reznik Michael , Scher Erica , Chang Andrew D , Frontera Jennifer , Lord Aaron , Rostanski Sara , Ishida Koto , Torres Jose , Furie Karen , Yaghi Shadi
Published: June 2021

Background and Purpose:
Early neurologic improvement (ENI) in patients treated with alteplase has been shown to correlate with functional outcome. However, the definition of ENI remains controversial and has varied across studies. Current definitions take into account the absolute difference between the admission and 24-hour NIHSS but this difference is usually not reported as a function of the baseline NIHSS. We hypothesized that ENI defined as a percentage change in NIHSS (percent change NIHSS) at 24-hours would better correlate with favorable outcomes at 3 months than ENI defined as the change in NIHSS (delta NIHSS) at 24 hours.

Methods:
Retrospective analysis of prospectively collected single center quality improvement data was performed of all acute ischemic stroke (AIS) patients treated with alteplase. Delta NIHSS was defined as the difference in admission and 24-hour NIHSS. Percent change NIHSS was defined as delta NIHSS divided by the admission NIHSS. We examined delta NIHSS and percent change NIHSS in unadjusted and adjusted logistic regression models as predictors of a favorable outcome at 3 months (defined as mRS 0-1).

Results:
Among 586 patients with AIS treated with alteplase with admission NIHSS, 24-hour NIHSS, and 3-month mRS available, 194 (33.1%) had a favorable outcome at 3 months. The mean age was 65 years and 59% were men. In fully adjusted models, both delta NIHSS (OR per point decrease 1.27; 95% CI, 1.19– 1.36) and percent change NIHSS (OR per 10 percent decrease 1.17; 95% CI, 1.12-1.22) were associated with favorable functional outcome at 3 months. Receiver operating characteristic (ROC) curve comparison showed that the area under the ROC curve for percent change NIHSS (0.755) was greater than delta NIHSS (0.613) or admission NIHSS (0.694).

Conclusion:
Percentage change in NIHSS may be a better surrogate marker of ENI and functional outcome in AIS patients after receiving acute thrombolytic therapy. More studies are needed to confirm our findings.
Abstract WP11: Timing of Blood Pressure Decreases During Mechanical Thrombectomy for Ischemic Stroke
Authors: Kimmel Alexandra C , Silverman Andrew , Kodali Sreeja , Strander Sumita , Nguyen Cindy Khanh , Peshwe Krithika Umesh , Wang Anson , Lopez Gloria V , Holcombe Andrea , Zevallos Cynthia , Dandapat Sudeepta , Sansing Lauren , Schindler Joseph , Falcone Guido , Matouk Charles , Sheth Kevin N , Ortega-Gutiérrez Santiago , Petersen Nils H
Published: June 2021

Introduction:
Decreases in blood pressure (BP) during endovascular therapy (EVT) are associated with infarct progression and poor outcome. The largest BP reductions are thought to occur during induction. The frequency and clinical relevance of late BP decreases after partial reperfusion has been achieved remain unknown. In this study, we aimed to characterize the timing of BP reductions during EVT and to assess their association with functional outcome.

Methods:
We retrospectively studied patients with LVO stroke who underwent EVT at two comprehensive stroke centers. BP was continuously monitored throughout the procedure and averaged for selected time points. Maximum BP drop was calculated as the difference between admission systolic BP (SBP) and lowest SBP during EVT and assigned to one of three intervals: 1) arrival to angiography suite to groin puncture, 2) groin puncture to first pass, and 3) first pass to recanalization. Functional outcome was assessed using the modified rankin scale (mRS) at 90 days. Associations with the outcome were analyzed using ordinal logistic regression and adjusted for the size of the maximum drop in SBP.

Results:
401 patients (age 71.3±14, 57% female, mean NIHSS 17) were included. Mean SBP for all patients decreased from EVT start to first procedural angiogram and then stabilized (Figure 1A). While the majority of blood pressure reductions occurred during interval 1 and 2 (n=253, 70%), 30% took place after first pass. We found no relation between timing of BP reduction and outcome (p=0.780, Figure 1B). Decreases in SBP during all intervals were significantly associated with 90-day outcome (OR per 10 mmHg 1.2, p=0.013; OR 1.1, p=0.025; and OR 1.3, p=0.011 for interval 1-3, respectively).

Conclusions:
BP drops occur throughout EVT, including between first pass and recanalization. Regardless of when these drops occur, they associate with poor outcome and thus underline the importance of blood pressure management throughout the procedure.