bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP405: Age, Race, and Gender Disparities in Door to Needle Time: A Single Center Joint Commission Certified Comprehensive Stroke Center Experience
Authors: Moore Kari D , Rock Peter , LIU Wei , Shah Jignesh , Wise Elizabeth , Remmel Kerri
Published: June 2021

Introduction:
Functional outcomes and quality of life are known benefits of Activase treatment in acute ischemic stroke (AIS), however, benefit is highly time dependent. Prior studies demonstrate that women and black patients with AIS are less likely to be treated with Activase in < 60 minutes. Utilization of best practice strategies identified in Target Stroke I & II has been an ongoing process improvement initiative at our facility since 2009.

Purpose:
Our goal was to understand if disparities in Door to Needle Time (DTNT) exist by age, race, or gender at our Joint Commission certified CSC with utilization of best practice strategies.

Methods:
A retrospective chart analysis with comparison of average DTNT by age, race and gender was performed on all AIS patients receiving Activase in our CSC from 2009-2015 (n=297). Differences in DTNT were analyzed using Student’s t-tests, ANOVA, and linear regression.

Results:
Median DTNT for all patients was 56 minutes (Male 58, Female 56, Black 61, and White 56). Average DTNT by age did not show any significant correlation with a R
2
=0.003 (F:0.98 p=0.322). Additionally, there were no significant differences among classified age categories (18-55, 56-80, 81-90, 91+; p=0.50). Average DTNT for females and males were observed to be 62.6 (95% CI 58.6-66.7) and 61.0 (95% CI 57.1-65.0), (p=0.57). Average DTNT for Blacks and Whites were observed to be 64.9 (95% CI 56.8-73.0) and 61.1 (95% CI 58.1-64.2), (p=0.35). Further analysis of gender by race classification demonstrated no significant differences in average DTNT (Black-Female 66.7, Black-Male 64.0, White-Female 62.1, White-Male 60.4 - F:0.44 p=0.73).

Conclusion:
No disparities in DTNT were found for age, race or gender at our CSC from 2009-2015. Target Stroke may have contributed to the absence of disparities. Comparison of DTNTs by age, race and gender before and after instituting Target Stroke at our CSC, other certified centers, and non-certified centers, is planned for our region. Further analyses will include arrival mode, payer source, stroke severity on arrival, off hour presentation, symptomatic hemorrhagic transformation rates, functional outcomes, and discharge disposition.
Abstract WP424: Let7i Microrna Regulates Immune Response in Patients with Ischemic Stroke
Authors: Jickling Glen C , Ander Bradley P , Shroff Natasha , Stamova Boryana , Dykstra-Aiello Cheryl , Zhan Xinhua , Liu Dazhi , Sharp Frank R
Published: June 2021

Background and Purpose:
The immune system responds rapidly following ischemic brain injury and can contribute to the final extent of brain damage. microRNA are differentially expressed in leukocytes following ischemic stroke and may regulate the immune response to ischemic brain injury. In this study we evaluate microRNA let7i-5p in ischemic stroke and its regulation of leukocytes.

Methods:
A total of 212 patients were studied; 106 with acute ischemic stroke and 106 risk factor matched controls. . RNA from circulating leukocytes was isolated from blood collected in PaxGene tubes. Let7i-5p miRNA expression was assessed by Taqman qRT-PCR. Given microRNAs act to destabilize and degrade their target mRNA, mRNA that inversely correlated with let7i were identified. To demonstrate let7i post-transcriptional regulation of target genes, a 3’UTR luciferase assay was performed. Target protein expression was assessed by ELISA.

Results:
Let7i was decreased in patients with acute ischemic stroke (fold change -1.70, p<0.00001). A modest inverse correlation between let7i and NIH Stroke Scale at admission (r= -0.32, p=0.02), infarct volume (r= -0.21, p=0.04) and plasma MMP9 (r= -0.46, p=0.01) was identified. The decrease in let7i was associated with increased expression of several of its messenger RNA targets including CD86, CXCL8 and HMGB1.
In vitro
studies confirm let7i post-transcriptional regulation of target genes CD86, CXCL8 and HMGB1. Functional analysis predicted let7i regulates pathways involved in leukocyte activation, recruitment, and proliferation including canonical pathways CD86 signaling in T helper cells, HMGB1 signaling, and CXCL8 signaling.

Conclusions:
Let7i is decreased in circulating leukocytes of patients with acute ischemic stroke. Mechanisms by which let7i regulates inflammatory response post-stroke include targeting CD86, CXCL8 and HMGB1.
Abstract WP425: Effects of Angiotensin II on Expression and Processing of Amyloid Precursor Protein in Human Cerebral Microvascular Endothelial Cells
Authors: Sun Ruohan , He Tongrong , Pan Yujun , Katusic Zvonimir
Published: June 2021

Background and Purpose:
Molecular mechanisms underlying increased risk of Alzheimer’s disease in hypertensive patients are poorly defined. Conflicting results have been reported regarding the effects of angiotensin II (Ang II) on expression of amyloid precursor protein (APP) and enzymes responsible for proteolytic cleavage of APP in the brain. However, no previous studies have directly assessed the effects of Ang II on metabolisms of APP in human endothelial cells. Current study was designed to determine the effects of Ang II on the expression and processing of APP in cultured human brain microvascular endothelial cells (hBMECs).

Methods:
Human BMECs were treated with increasing concentrations of Ang II (0.1nM to 100nM; incubation time = 24h). The protein expression of APP, α-secretase [a disintegrin and metalloprotease 10, (ADAM10), ADAM9, and ADAM17], β-secretase (β-site APP-cleaving enzyme, BACE1), NADPH oxidase subunits and endothelial nitric oxide synthase (eNOS) were measured by western blot. Production and release of amyloid β-peptides (Aβ) from endothelium were detected by ELISA.

Results:
In hBMECs, Ang II had no effect on the expression of APP (n=7-9, P>0.05) and α-secretase (ADAM10, n=7-9, P>0.05; ADAM9, n=4-7, P>0.05; ADAM17, n=4-7, P>0.05). Treatment with Ang II at 1nM concentration induced significant increase in BACE1 expression (n=13, P<0.05), however, we did not observe significant changes in production of Aβ40 (n=11, P>0.05) or Aβ42 (n=11, undetectable). The higher concentration of Ang II (100nM) increased expression of NOX4 (n=6, P<0.05). In addition, Ang II (1nM and 10nM) significantly up-regulated eNOS protein levels (n=8-10, P<0.05).

Conclusion:
Our findings suggest that in hBMECs: a) Ang II does not affect expression of APP and α-secretase-mediated cleavage of APP, and b) Ang II increases expression of BACE1 but does not elevate production and release of Aβ peptides. We also confirm previously reported ability of Ang II to increase expression of NOX4 and eNOS. We speculate that under pathological conditions, increased expression of BACE1 induced by Ang II may predispose cerebrovascular endothelium to elevated amyloidogenic processing of APP.
Abstract WP430: Endothelial Cell Collection from Ipsilateral Middle Cerebral Artery in Acute Ischemic Stroke
Authors: Sheth Sunil A , Verma Abhishek , Liebeskind David S , Saver Jeffrey L , Duckwiler Gary , Tateshima Satoshi , Szeder Viktor , Jahan Reza , Hinman Jason
Published: June 2021

Introduction:
The cerebrovascular endothelium plays a critical role in the pathogenesis of and response to acute ischemic stroke (AIS). To date, techniques to study its function have relied on animal and in vitro models. A robust method of endothelial cell (EC) capture in patients with AIS at early time points, from within the ischemic region, could greatly advance our understanding of cerebrovascular injury.

Method:
Patients undergoing thrombectomy for middle cerebral artery occlusion (MCA) within 8 hours of onset were offered enrollment if the pass of their stent-retriever device occurred directly into a distal access catheter in the proximal M1 segment, limiting exposure of the device to only the MCA. After retrieval, ECs adherent to the devices were retrieved and stained for EC (CD31) and leukocyte (CD45) markers. EC identity and yield were confirmed by flow cytometry with simultaneous immuno-fluorescence microscopy. Cultured human ECs were used as positive controls. The EC fraction was defined as CD31
+
CD45
-
with size and morphological features consistent with the positive controls.

Results:
ECs from stent-retriever devices (n=3) were collected and pooled. Approximately 8% of the collected cells represented ECs. EC collected from the stent-retrievers demonstrated highly similar shape, morphology and antibody staining patterns compared to the positive controls (Figure).

Conclusions:
Here we provide the first demonstration of a rapid post-thrombectomy method for reliable harvesting of cerebral ECs in humans. The ability to capture these cells in patients with AIS within hours of symptom onset opens many avenues of exploration for determining the role of ECs in AIS.
Abstract WP432: Non-invasive Respiratory Impedance Enhances Cerebral Perfusion
Authors: Favilla Christopher G , Parthasarathy Ashwin B , Detre John A , Mullen Michael T , Kasner Scott E , Yodh Arjun G , Gannon Kimberly , Messe Steven R
Published: June 2021

Background:
Optimization of cerebral blood flow is the cornerstone of clinical management in a number of neurologic diseases, most notably ischemic stroke. Intra-thoracic pressure influences cardiac output and has the potential to impact cerebral blood flow (CBF). Here we aim to quantify cerebral hemodynamic changes in response to increased respiratory impedance using a non-invasive respiratory device.

Methods:
Cerebral perfusion was measured under varying levels of respiratory impedance (6cm H
2
0, 9cm H
2
0, and 12 cm H
2
0) in 20 healthy volunteers. Simultaneous measurements of microvascular CBF and middle cerebral artery mean flow velocity (MFV), respectively, were performed with optical diffuse correlation spectroscopy (DCS) and transcranial Doppler ultrasound (TCD).

Results:
At the high level of respiratory impedance, mean flow velocity increased by 6.4% compared to baseline (p=0.004), but changes in cortical CBF were smaller and non-significant (Figure). Heart rate, cardiac output, respiratory rate, and end tidal CO
2
remained stable during all levels of respiratory impedance. There was small increase in mean arterial blood pressure, 1.7% (p=0.006), at the high level of respiratory impedance. In a multivariable linear regression model accounting for end tidal CO
2
and individual variability, respiratory impedance was associated with increases in both mean flow velocity (coefficient: 0.49, p<0.001) and cortical CBF (coefficient: 0.13, p<0.001).

Conclusions:
Manipulating intrathoracic pressure via non-invasive respiratory impedance was well tolerated and produced a small but measurable increase in cerebral perfusion in healthy individuals. Future studies in acute ischemic stroke patients with impaired cerebral autoregulation is warranted in order to assess whether respiratory impedance is feasible as a novel non-invasive therapy for stroke.
Abstract WP437: Sleep Apnea and Cerebral Blood Flow: the Role of Autoregulation
Authors: Rostanski Sara K , Westwood Andrew J , Baboli Mehran , Marshall Randolph S
Published: June 2021

Objective:
Obstructive sleep apnea (OSA) is a stroke risk factor and is increasingly recognized as a risk factor for cognitive impairment. Altered cerebral autoregulation may play a role in these relationships. We measured the association between OSA and two forms of cerebral autoregulation: (1) dynamic cerebral autoregulation (DCA), which plays a homeostatic role; and (2) vasomotor reactivity (VMR), which is a measure of cerebrovascular reserve. We hypothesized that both VMR and DCA would be impaired in subjects with OSA.

Methods:
We recruited subjects with untreated OSA. VMR and DCA were measured with continuous transcranial Doppler (TCD) of the middle cerebral arteries (MCA). DCA was measured with phase shift analysis where lower degrees of phase shift indicate greater impairment; values <24 degrees are abnormal. VMR was measured as % change in MCA velocity in response to 5% CO2 inhalation; values <2% change are abnormal. We assessed the relationship between apnea-hypopnea index (AHI) and autoregulation using bivariate correlations (Pearson coefficient). We also assessed the association between moderate to severe OSA (AHI≥15) and abnormal autoregulation (Fisher’s exact test).

Results:
Twelve subjects were enrolled; 11 had TCD data. Mean age was 53 (SD 11) and the majority had moderate to severe OSA (median AHI 27, IQR 16-37). Mean VMR (% change in MCA velocity) was 3.1 (SD 0.7); mean phase shift was 34 degrees (SD 15). There was a moderate association between AHI and phase shift (r=-0.40); the correlation with VMR was weaker (r=-0.25). The proportion of subjects with abnormal DCA was greater among those with moderate-severe OSA compared to those with mild OSA (66.7% vs. 0%, p=0.2). No enrolled subjects had abnormal VMR.

Conclusion:
Moderate to severe OSA is associated with abnormal dynamic cerebral autoregulation and normal vasomotor reactivity. The mechanism underlying this dissociation may involve OSA-mediated inflammation and endothelial dysfunction. Further study may clarify how this dissociation relates to increased risk of cerebral ischemia among patients with OSA.
Abstract WP48: Relationship of Cerebral Blood Flow by Pseudo-continuous Arterial Spin Labeling and Stenosis in Middle Cerebral Artery Territory in Patients Evaluated for Acute Ischemic Stroke
Authors: Lai Eric , Aman Raja Rizal Azman Raja , Zhang Hui , Chiu Pui-Wai , Chan Queenie , Chan Bernard , Mak Henry Ka-Fung
Published: June 2021

Purpose:
Correlation of arterial stenosis with cortical and subcortical cerebral blood flow (CBF) in the middle cerebral artery (MCA) territory.

Methods:
126 patients with acute cerebrovascular symptoms from March to June 2015 underwent MRI and MR Angiography (MRA) in a University hospital using a 3.0 Tesla scanner. Sequences included T1W, T2W, FLAIR, DWI, MRA, Pseudocontinuous Arterial Spin Labeling (pcASL, post-labeling delay 1.525 s). 13 patients (corrupted pcASL data) were excluded, with 113 patients (mean age: 67.74±14.19) evaluated (61 acute ischemic stroke, 52 patients transient ischemic attack). Institutionally developed software was used to determine CBF. MCA stenosis was graded into 4 categories by a neuroradiologist: 0 (no stenosis), 1 (mild <50%), 2 (moderate 50-70%) and 3 (severe >70%). Mean and standard deviation of MCA categories (leptomeningeal and perforating) CBF and corresponding degree of MCA stenosis were measured. Spearman correlation coefficients between CBF of cortical and subcortical regions and degree of MCA stenoses were calculated using SPSS (version 23.0).

Results:
The table showed the descriptive statistics. There was significant correlation between CBF of cortical region of MCA vascular territory and degree of stenosis of MCA in both left (r
s
= -0.296,
p
=0.001) and right (r
s
= -0.306,
p
=0.001) side. In the contrary, there was no correlation between subcortical CBF of MCA vascular territory and degree of stenosis of MCA in both sides.

Conclusion:
pcASL is a feasible non-invasive method to measure CBF in clinical setting. In MCA territory, the cortical blood flow correlated (fairly) with large vessel stenosis but not subcortical flow. We conclude that cortical CBF correlated with large artery stenosis, though being attenuated by collateral blood supply. No such relationship in subcortical CBF might be due to differential grey and white matter CBF flow, variable MCA stenotic location, and perforators originating from other territories.
Abstract WP49: Performance of CT, CTA, and MRI on Decision to Treat Emergent Large Vessel Occlusion (ELVO) in Patients who Present Greater Than 6 Hours After Stroke Onset
Authors: DiBiasio Eleanor L , McTaggart Ryan A , Baird Grayson L , Yaghi Shadi , Tung Eric L , Hidlay Douglas T , Hemendinger Morgan L , Tung Glenn A , Jayaraman Mahesh V
Published: June 2021

Background and purpose:
We compared the value of Alberta Stroke Program Early Computed Tomographic scoring using CT (CT ASPECTS), collateral score on CT angiography (CTA), ASPECTS using diffusion-weighted MRI (DWI ASPECTS), DWI lesion volume, and DWI volume with National Institute of Health Stroke Scale (NIHSS) in determining candidacy of patients who presented >6 hours from stroke onset.

Methods:
Decision to treat was first determined for each test alone and then with knowledge from other tests. A dismantling design was used to determine the additive effects of each test. Any discrepancy between the first and subsequent decisions to treat, in terms of sensitivity and specificity, is the impact of gained knowledge and was assessed using a generalized mixed-model assuming a binary distribution with PROC GLIMMIX/SAS. Inter-rater reliability was examined using weighted-Kappa.

Results:
We identified 39 patients between December 1st, 2015 and June 30th 2016. Median time from last-known normal to non-contrast CT was 492 minutes. Median interval between non-contrast CT and CTA was 7 minutes, and between CTA and MRI, 75.5 minutes. For sensitivity, effect of knowledge gained from successive tests was not significant (Table 1; Fig. 1). However, significant gains in specificity were observed from successive tests (63% to 84%; p<.01). In particular, specificity increased by 14% (p=.09), 18% (p=.02), and 12% (p=.07), for DWI ASPECTS, DWI Volume, and DWI Volume+NIHSS, respectively. Inter-rater reliability was between .34-1.0 for each test.

Conclusion:
CT, CTA and MRI each have the ability to correctly determine ELVO patients who would be candidates for embolectomy. However, identification of poor candidates for endovascular therapy was significantly improved using diffusion-weighted MRI.
Abstract WP51: Neurological Severity and Infarct Size in Patients With Acute Ischemic Stroke During DOAC Treatment for Nonvalvular Atrial Fibrillation
Authors: Shibata Yo , Nakamura Asako , Yasaka Masahiro , Kuwashiro Takahiro , Gotoh Seiji , Takaguchi Go , Nakanishi Yasuyuki , Okada Yasushi
Published: June 2021

Background and purpose:
Less severe and smaller infarct are features in acute stroke patients treated with warfarin within a therapeutic range of PT-INR than in those without. But it remains unclear the severity and size of infarct in acute stroke patients treated with direct oral anticoagulants [DOAC]. We investigated the features of acute stroke in patients treated with DOAC, warfarin or without.

Methods:
We enrolled consecutive 190 non-valvular atrial fibrillation patients (mean age 78; 63% male) who developed acute ischemic stroke and classified them into 4 groups, 109 patients with no anticoagulant therapy [Control group], 25 patients with DOAC therapy [DOAC group], 19 patients treated with warfarin within a therapeutic range of PT-INR [>= 1.6 in patients aged 70 years old or older, >= 2.0 in those aged younger than 70 years old, Warfarin well controlled group], and 37 patients treated with warfarin with subtherapeutic PT-INR values [Warfarin not controlled group]. Infarcts sizes were defined as the maximum diameter of infarct, using the brain MRI diffusion-weighted image. Stroke severity on admission were assessed by the National Institutes of Health Stroke Scale[NIHSS].We compared them among the groups.

Results:
There were no significant differences in preadmission CHADS2 score among the 4 groups. The median infarct size were 31mm (interquartile (IQR) 13-59) in the control group, 10mm (IQR 7.4-38) in the DOAC group, 12mm (IQR 8.0-45) in the warfarin well controlled group, and 24mm (IQR 13-67) in the warfarin not controlled group. The size of infarct was significantly smaller in the DOAC group than the control group (P=0.01). The NIHSS on admission was 4 ([IQR] 2-15) in the control group, 2 (1-6) in the DOAC group, 4 (1-17) in the warfarin well controlled group and 5 (3-17) in e warfarin not controlled group. Stroke severity on admission was also more favorable in the DOAC group when compared with the control group (P=0.03)

Conclusions:
Smaller and less severe infarct may be feature of acute ischemic stroke during DOAC therapy when compared to that without any anticoagulant therapy.
Abstract WP53: The prognostic value of Posterior Circulation Acute Stroke Prognosis Early Ct Score (pcaspects) on CT perfusion in patients with basilar artery occlusion
Authors: Alemseged Fana , Shah Darshan G , Diomedi Marina , Bivard Andrew , Sharma Gagan , Sallustio Fabrizio , Mitchell Peter J , Dowling Richard J , Yan Bernard , Stanzione Paolo , Parsons Mark W , Levi Christopher R , Davis Stephen M , Campbell Bruce C
Published: June 2021

Background:
CT perfusion (CTP) increases diagnostic confidence in ischaemic stroke. Despite bone-related artefacts, CTP has been shown to improve diagnostic sensitivity compared to non contrast-CT (NCCT) and Computed Tomography Angiography source images (CTA-SI) in posterior circulation strokes. The posterior circulation Acute Stroke Prognosis Early CT score (pcASPECTS) on CTA-SI predicts clinical outcome in patients with basilar artery occlusion (BAO). We assessed the prognostic value of pcASPECTS on CTP in BAO patients.

Methods:
A retrospective analysis of consecutive patients with BAO diagnosed on CT angiography was performed. pcASPECTS was assessed as evident hypoattenuation on CTA-SI, focally reduced cerebral blood flow (CBF) or cerebral blood volume (CBV), focally increased time to peak of the residue function (Tmax) or mean transit time (MTT). Two investigators independently reviewed the images blinded to clinical outcome. Reliability was assessed with intraclass correlation coefficient (ICC). Good outcome was defined as modified Rankin Scale≤3 at 3 months.

Results:
We included 43 BAO patients with whole-brain CTP images. In receiver-operating-characteristic (ROC) analysis, the area-under-curve (AUC) was 0.79 (95% CI 0.6-0.9) for pcASPECTS on CBF, 0.77 (95% CI 0.6-0.9) on Tmax, 0.73 (95% CI 0.6-0.9) on MTT, 0.72 (95% CI 0.6-0.9) on CBV, 0.67 (95% CI 0.5-0.8) on CTA-SI. In logistic regression adjusted for age and clinical severity, pcASPECTS<8 was associated with poor outcome on Tmax (OR 14.6, 95% CI 2.3-115; p=0.007) and CBF (OR 15.1, 95% CI 1.3-121; p=0.02). Although CTP AUC did not show higher accuracy in comparison with CTA-SI AUC (p=0.2), in logistic regression, CTA-SI pcASPECTS was not significantly associated with clinical outcome (OR 6.9, 95% CI 0.7-70; p=0.1, adjusted for age, NHSS). Higher pcASPECTS on CBF (OR 0.5 95%CI 0.2-0.9, p=0.04) and Tmax (OR 0.5 95% 0.3-0.9; p=0.02) were associated with lower mortality. Interrater reliability was good for CTP maps (ICC between 0.74 and 0.86 95% CI

0.6-0.9 versus 0.66 for CTA-SI 95% CI 0.4-0.8).

Conclusions:
The CTP pcASPECTS may identify BAO patients at higher risk of disability and mortality.
Abstract WP57: Perfusion Angiography Improves Clinical Outcomes Prediction in Endovascular Stroke Therapy
Authors: Sheth Sunil A , Weng Julius , McElhinney Priscilla , Quachtran Benjamin , Liebeskind David S , Saver Jeffrey L , Duckwiler Gary , Scalzo Fabien
Published: June 2021

Background:
Successful reperfusion is a key determinant of outcome in endovascular stroke therapy (ET). However, present methods of grading treatment success using the Thrombolysis in Cerebral Infarction (TICI) scale fail to measure quantitative changes in cerebral blood flow and volume (CBF and CBV) and as such, may not fully represent treatment effect.

Methods:
From our prospectively maintained institutional registry, we identified patients treated with ET between February 2014 and May 2016. CBF and CBV maps were calculated automatically for both AP and Lateral projections and regions of interest (ROIs) were drawn by two experienced neuroimagers over the middle cerebral artery territories. Delta CBF and CBV scores were determined by subtracting pre- from post-intervention maps and averaging over the ROIs. Non-linear regression was used to calculate correlations against clinical outcome (modified Rankin scale at discharge).

Results:
Among 104 patients treated with ET, average age was 70, 50% were female, and median presentation NIHSS was 16 (IQR 10-19). Target occlusion location was ICA in 14%, M1 in 67%, and M2 in 18%. TICI scores ranged from 0 (4%), 1 (13%), 2a (2%), 2b (22%), 3 (58%). Relative increases in CBF and CBV ranged from 0.4-17% (CBF) and 0.3-14% (CBV). Delta CBF and CBV maps correlated well with angiographic TICI (CBF p<0.05, CBV p<0.05). TICI alone did not correlate significantly with outcome (r=0.24, p=0.14). However, including delta CBF and CBV with TICI resulted in a stronger correlation (r=0.37, p<0.05) against outcome.

Conclusions:
TICI is an important determinant of outcome in EST. The incorporation of perfusion angiography measurements (CBF and CBV) improves the predictive power of angiography for clinical outcome.
Abstract WP61: Volumetric DWI Malignant Profile Assessment in Acute Ischemic Patients With Reperfusion Therapy.
Authors: Inoue Manabu , Wada Shinichi , Sonoda Kazutaka , Yoshimura Sohei , Sato Shoichiro , Hayakawa Mikito , Yamagami Hiroshi , Nagatsuka Kazuyuki , Toyoda Kazunori
Published: June 2021

Background:
The efficacy of endovascular therapy (EVT) in acute stroke has been established but the imaging criteria have not yet been assessed. Malignant profile is a magnetic resonance imaging (MRI) pattern that is associated with poor outcomes. We estimated this profile by volumetrically assessing diffusion weighted image (DWI) in patients treated with reperfusion therapy including intravenous tissue plasminogen activator (IV tPA) and endovascular therapy (EVT).

Methods:
Acute anterior ischemic stroke patients with baseline DWI before reperfusion therapy were included. Outcome was assessed by modified Rankin Scale (mRS) at discharge. DWI volume was measured by semi-automated software.Receiver operating characteristic (ROC) curve analysis was performed to identify optimal DWI volumes with poor outcome (mRS 5-6).

Results:
Total of 96 patients (43% women, mean age 72±13 years) were included in this study. Median (interquartile range: IQR) National Institutes of Health Stroke Scale was 9 (5-12) and median onset to MRI time was 108.5 (70-217) minutes. Median DWI volume was 4.4 (1.3-17) mL for overall patients. Median onset to IV tPA time for 60 (63%) patients were 120 (65-177) minutes. Median onset to puncture time for 36 (38%) EVT-treated patients was 208 (121.0-474.3) minutes; 29 of these 36 patients (81%) had Thrombolysis in Cerebral Infarction (TICI) score of 2B/3. Median discharge mRS was 2 (1-3) for overall and 6 cases (6%) had mRS 5-6. ROC analysis determined DWI volume with poor outcome as 49.5 mL (92.2% specificity and 50% sensitivity, AUC 0.75, p<0.001).

Conclusion:
Our study suggests the optimal volume of the malignant profile on DWI was approximately 50mL in reperfusion therapy eligible patients. Clinical outcome of patients exceeding the cutoff volume were very poor. The imaging criteria for reperfusion therapy including EVT should be well considered to achieve better outcomes.
Abstract WP83: Wall Shear Stress Strength Over the Cerebral Aneurysm is Drastically Affected by Aneurysm Location While the Magnitude of Disturbed Flow is Closely Related to Aneurysm Size and Surface Area
Authors: Fukuda Shunichi , Shimogonya Yuji
Published: June 2021

Background and purpose:
The rupture rate of cerebral aneurysms varies according to the aneurysm size and location. Although several reports suggest hemodynamic involvement in the mechanisms, there still remains to be clarified. Using computational fluid dynamics, we elucidated here differences in hemodynamics according to size and location of human cerebral aneurysms.

Methods:
Patient-specific inflow velocities and arterial geometries of 39 MCA aneurysms and anterior communicating artery (Acom) aneurysms were acquired from patients who consented to participate in the multi-institutional prospective clinical study, CFD ABO Study. Pulsatile blood flow was simulated using ANSYS-CFX, based on the Navier-Stokes equations for incompressible fluid. Aneurysms were divided into 3 groups by their size; less than 5mm, less than 7mm and more than 5mm, and more than 7mm.

Results:
Wall shear stress (WSS) was significantly lower in Acom aneurysms than MCA aneurysms (p=0.00075) while there was no significant difference in WSS according to aneurysm size. In contrast, indicators for disturbed flow, oscillatory shear index (OSI) and normalized transverse WSS (NtransWSS) were significantly higher over the aneurysms of the size less than 7mm and more than 5mm compared to those less than 5mm (p=0.021 and 0.014, respectively). Moreover, there were strong or moderate positive correlations between aneurysm surface area and OSI and NtransWSS, but not WSS. However, there was no significant difference in OSI or NtransWSS between MCA and Acom aneurysms.

Conclusions:
The data suggest that WSS strength over the cerebral aneurysm is drastically affected by the aneurysm location while the magnitude of disturbed flow is closely related to aneurysm size and surface area. A significant lower WSS in Acom aneurysms compared to MCA aneurysms may be associated with higher rupture rate in Acom aneurysms. In contrast, disturbed flow may be involved in aneurysm enlargement.
Abstract 118: Factors and Hospital Charges Associated With Prolonged Length of Hospitalization in Patients Admitted With Ischemic Stroke in the United States
Authors: Chaudhry Saqib A , Chaudhry Mohammad Rauf A , Akhtar Iqra N , Gill Mohsain , Qureshi Adnan I
Published: June 2021

Background and Purpose:
The duration of hospitalization and associated factors are not well studied in national cohorts. We identified the proportion and determinants of prolonged hospitalization and determined the impact on hospital charges using nationally representative data.

Methods:
National estimates of length of stay, mortality, and hospital charges incurred in patients admitted with primary diagnosis of ischemic stroke (ICD-9 CM diagnosis-related code 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434.01, 434.11, 434.91, and 436) using Nationwide Inpatient Sample data from 2010 to 2015. Nationwide Inpatient Sample is the largest all-payer inpatient care database in the United States. Patient who were transferred from another acute hospital or had mortality within 2 days of admission were excluded from the analysis. All the variables pertaining to hospitalization were compared in four quartiles based on distribution data for length of hospital stay (≤2, 3 to 4, 5 to 6 and ≥7 days).

Results:
A total of 2,490,136 patients were admitted with the diagnosis of ischemic attack during the study period. The median length of stay for hospitalization was 4 days. The length of hospitalization was ≤2, 3 to 4, 5 to 6 and ≥7 days in 706,550 (28.4%), 842,872 (33.8%), 417,592 (16.8%) and 523,122 (21.0%) patients, respectively. The mean hospitalization charges were $22,819, $32,593, $ 45,486 and $97,868 for patients hospitalized in four quartiles, respectively. In the multivariate analysis, the following patient factors and in hospital complications were associated with above median length of hospitalization of ≥4 days: age >65 years (odds ratio [OR], 1.06), women (OR, 1.07), history of alcohol use (OR, 1.29), deep venous thrombosis (OR, 2.67), urinary tract infection (OR, 1.68), pneumonia (OR, 1.53), sepsis (OR, 1.85), pulmonary embolism (OR, 1.48), admission to urban teaching hospitals (OR, 1.07), Medicaid insurance (OR, 1.53), and hospital location in Northeast US region (OR, 1.86; all P values <0.0001).

Conclusions:
The hospital stay in more than half of patients admitted with ischemic stroke is 4 days or greater. Strategies that focus on modifiable factors associated with prolonged hospital stay may reduce the hospitalization charges in United States.
Abstract 124: Supplementation With Growth Differentiation Factor11 Promotes Tissue Recovery and Angiogenesis After Ischemic Stroke in Aged Mice
Authors: Hudobenko Jacob , Ganesh Bhanu Priya , Jiang Jianjun , Mohan Eric , Lee Songmi , Sheth Sunil , Morales-Scheihing Diego , Zhu Liang , Kofler Julia , Pautler Robia , McCullough Louise , Chauhan Anjali
Published: June 2021

Introduction:
Growth differentiation factor (GDF) 11 levels decline with aging. This age-related loss of GDF11 has been implicated in a variety of age-related diseases. Supplementation with GDF11 reverses cardiac hypertrophy, bone loss, and pulmonary dysfunction in old mice, suggesting a rejuvenation effect of GDF11.

Hypothesis:
Brain levels of GDF11 would decline in aged animals, and that stroke would accelerate the age-related loss of GDF11. Exogenous administration of GDF11 would improve stroke outcomes in old mice.

Methods:
GDF11/8 levels were assessed in young and old mice and in postmortem human brain samples. In older mice, five days after MCAO, GDF11, and BrdU were administered for five days. Neurobehavioral assessments were performed during stroke recovery. MRI was used to determine cerebrospinal fluid (CSF), corpus callosum (CC) area, and percentage of brain tissue loss. Ten days post MCAo, brain expression of claudin5, collagen IV, BDNF, VEGF, pSmad2/3, activin type IIb receptor was assessed by western blotting. We performed immunohistochemistry to investigate IBA1, GFAP, NeuN, doublecortin, BDNF, MBP, synaptophysin, and CD31 immunoreactivity 30 days post-MCAo.

Results:
A decline in brain GDF11/8 was seen with age and after stroke in both mice and humans (p<0.05). Exogenous GDF11 supplementation reduced mortality and improved sensorimotor deficits thirty days after stroke. Treatment resulted in a reduction (p<0.05) in brain atrophy and CSF volume, and increased corpus callosum thickness as assessed by MRI. GDF11 treatment reduced gliosis, increased angiogenesis, and improved white matter integrity in aged mice.

Conclusions:
Brain GDF11/8 levels are reduced with aging, and after stroke. Exogenous GDF11 supplementation reduced mortality, decreased brain tissue damage, improved sensorimotor deficits, reduced gliosis, and increased angiogenesis in old mice after stroke.
Abstract 129: Endovascular Thrombectomy Potential Benefits in Isolated M2 Occlusions Are Related to Stroke Severity and Penumbral Mismatch Deficit: A Secondary Analysis From the SELECT Study
Authors: Sarraj Amrou , Hassan Ameer , Grotta James C , Sitton Clark , Blackburn Spiros , Abraham Michael , Chen Peng R , Vora Nirav , Pujara Deep , Cai Chunyan , Parsha Kaushik , Reddy Sujan , Kamal Haris , Arora Ashish , Imam Bita , Hicks William J , Shaker Faris , Barreto Andrew D , Riascos Roy F , Haussen Diogo , Martin-Schild Sheryl , Gupta Rishi , Lansberg Maarten , Savitz Sean I , Albers Gregory W
Published: June 2021

Background:
The efficacy of endovascular thrombectomy (EVT) in M2 occlusions is uncertain.

Methods:
In a prospective multicenter cohort study of imaging selection (SELECT), EVT outcomes were compared to medical managment (MM) in M2 occlusions. Further, we assessed for potential treatment benefit in patients with higher stroke severity (NIHSS) and a larger perfusion deficit on CTP (Tmax > 6 sec - ischemic core volume)The primary outcome was excellent outcome (mRS 0-1).

Results:
of 361 patients enrolled in SELECT, 87 had isolated M2 occlusion (EVT 59, MM 28). Baseline NIHSS median (IQR) (EVT 14 (10-20), MM 15 (9.5-19.5), p=0.72) and infarct volume rCBF<30% (EVT 7 (0-21) vs MM 18.5 (0-41.25), P=0.10). EVT was associated with higher rates of excellent outcomes (53% vs 21%, aOR:6.94, 95% CI=1.86-25.90, p=0.004) with a shift towards better mRS outcomes (adj cOR: 3.49, 95% CI=1.39-8.80, p=0.008), smaller final infarct volume (15.9 (2.7-48.0) vs 58 (24.3-141.9), P<0.001), and a reduction of neurological worsening (3% vs 22%, p=0.011), sICH (2% vs 21%, p=0.004), and mortality (5% vs 25%, p=0.011). Assessing outcomes in NIHSS strata; there was no significant increase in excellent outcomes rates in NIHSS ≤10 (EVT 65% vs MM 50%, aOR=1.59, 95% CI=0.21-12.01, p=0.65). In contrast, patients with NIHSS>10 had better outcomes with EVT (46%) vs MM (10%), aOR=11.39, 95% CI=1.80-72.11, p=0.01 as shown in figure 1. As perfusion deficit lesion size increased, the odds of achieving excellent outcomes was reduced (for each 10cc by 11%, aOR: 0.89, 95% CI=0.79-1.00, p=0.05). Excellent outcomes declined in patients with MM as perfusion deficit lesion size increased, yet in the EVT they were maintained as shown in figure 2. Similar results were obtained for mRS 0-2.

Conclusion:
EVT may result in better rates of excellent outcomes in isolated M2 occlusions, especially those with more severe strokes and larger perfusion deficits who are more likely to have worse outcomes without emergent reperfusion.
Abstract 149: Successful Reperfusion After Endovascular Treatment Predicted Favorable Outcome in the Basilar Artery Occlusion Endovascular Intervention versus Standard Medical Treatment (BEST) Trial
Authors: Dai Qiliang , Xu Gelin , Liu Rui , Liu Xinfeng , Nogueira Raul
Published: June 2021

Background:
Several randomized trials have demonstrated a strong benefit of endovascular reperfusion in the anterior circulation strokes. The association between successful reperfusion and outcomes is less well established in acute vertebrobasilar artery occlusions (VBAO). We aim to investigate the association between successful reperfusion and 90-day favorable outcome in BEST trial.

Methods:
The BEST trial was a multicenter randomized controlled trial of endovascular treatment versus medical treatment alone in VBAO. In the current analysis, we included patients who underwent endovascular treatment in the As-Treated Population of our trial. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction Score (mTICI) 2b/3 post-intervention. Favorable outcome was defined as mRS 0-3. Logistic regression was used to investigate the association between successful reperfusion and outcome.

Results:
The trial was terminated prematurely in September-2017 after enrolling 131 patients due to a high cross-over rate (Control to the ET=14; ET to Control=3). A total of 77 patients received endovascular treatment were included in this analysis. Baseline characteristics and outcome measures according to Intention-To-Treat (IIT), Per-Protocol (PP), and As-Treated (AT) analyses are summarized in
Table 1
. Successful reperfusion was achieved in 70.1% (54/77) patients. Multivariable logistic regression adjusted for age and baseline NIHSS score showed that successful reperfusion was significantly associated with favorable outcome at 90 days (adjusted OR, 3.16; 95% CI, 1.05 to 9.48, p=0.04) as well as a strong trend towards lower 90-day mortality (adjusted OR, 0.36; 95% CI, 0.12 to 1.06, p=0.06).

Conclusion:
Endovascular reperfusion was associated with better 90-day functional outcome and a trend towards lower mortality in the BEST Trial.

Table 1: Baseline Characteristics and Outcomes Measures:
Abstract 156: Recurrent Stroke in Middle-Aged Lacunar Stroke Survivors: Understanding Risk Factors and Vulnerability in an Important Target Population
Authors: Noche Rommell B , Biffi Alessandro , Sansing Lauren H , Shoamanesh Ashkhan , Benavente Oscar R , Falcone Guido J , Sheth Kevin N
Published: June 2021

Background:
The precise role of stroke risk factors in middle-aged people remains a significant knowledge gap. Confounding risk factors conferred by young and elderly stroke are largely avoided, providing a unique opportunity to understand the relationship between traditional risk factors and stroke. We aimed to determine the predictors of stroke and myocardial infarction (MI) in a unique middle-aged cohort with MRI-defined lacunar stroke.

Methods:
We conducted a reanalysis of data from the Secondary Prevention of Small, Subcortical Strokes (SPS3) clinical trial. We focused on middle-aged study participants, defined as those aged 40-60 years at study entry. We used multivariate Cox regression models to estimate the risk of recurrent stroke or MI.

Results:
Out of 3,020 total subjects from SPS3, 1,312 (mean age 53 [SD 5], 445 females [34%]) were in the middle-aged category and were included in this analysis. Of these, there were 619 (47%) white, 297 (23%) black, and 283 (22%) Hispanic subjects. Over a mean follow-up time of 3.90 years, there were 123 strokes (2.6% per patient-year) and 33 MIs (0.7% per patient-year). The rates (% per patient-year) of having a stroke or MI differed significantly across white (n=59, 2.7%), black (n=54, 5.1%), and Hispanic (n=27, 2.8%) ethnic groups (p=0.006). Significant risk factors for recurrent stroke or MI are described for middle-aged and all SPS3 subjects in the table.

Conclusions:
In middle-aged individuals with prior stroke, diabetes, greater white matter disease severity, black race, and family history were potent predictors of recurrent stroke. Male sex, diabetes, and heart disease were potent predictors of MI. Compared to the entire SPS3 cohort, these predictors confer a greater risk for recurrent stroke or MI in the middle-aged. These data identify modifiable risk factors and target populations that are especially vulnerable to vascular events or complications.
Abstract 161: Prevalence and Course of Depression During the First Year After Stroke
Authors: Dong Liming , Williams Linda , Brown Devin , Case Erin , Morgenstern Lewis , Lisabeth Lynda
Published: June 2021

Introduction:
Depression is prevalent and burdensome in stroke survivors, however, information about its longitudinal course following stroke is limited, especially for the early stage of stroke recovery. The study examined changes in the prevalence and patterns of depression during the first year after stroke.

Methods:
Data were obtained from the Brain Attack Surveillance in Corpus Christi (BASIC) project (2011-2016), a population-based stroke surveillance study in south Texas. Depressive symptoms at 3, 6 and 12 months post-stroke were assessed using the 8-item Patient Health Questionnaire (range: 0-24); scores≥10 classified as having depression. Cross-tabulations were used to estimate prevalence of depression, and latent transition analysis was used to examine changes in symptom patterns.

Results:
A total of 684, 574 and 563 participants had complete data at 3, 6 and 12 months, respectively. Mean age was 65.9 (SD=11.2), women and men were evenly distributed, and approximately three-fifths were Mexican American. Prevalence of depression after stroke was 35.2% at 3 months, decreased to 24.4% at 6 months, and remained stable at 25.9% at 12 months. Four latent classes of depressive symptom patterns were identified (Table). There were more transitions from the fatigue and sleep predominant and severe symptom groups to mild and slight/no symptom groups between 3 and 6 months than between 6 and 12 months. The majority of the slight/no symptom group retained this pattern over time; whereas a substantial proportion of the mild symptom group developed more severe symptoms, especially after 6 months.

Conclusions:
Prevalence of depression peaks at 3 months after stroke, declines thereafter but remains stable and high after 6 months. The course of post-stroke depression is heterogeneous and dynamic. Further research should identify the characteristics of group membership in stroke patients to provide evidence for targeted screening and personalized treatment.
Abstract 177: Brain-Wide Circuit Dynamics of Post-Stroke Recovery After Optogenetic Stimulation
Authors: Cheng Michelle Y , Vahdat Shahabeddin , Pendharkar Arjun V , Harvey Sean , Chiang Terrance , Lee Hyun Joo , Lee Jin Hyung , Steinberg Gary K
Published: June 2021

Background:
Post-stroke optogenetic stimulations have been shown to promote functional recovery. However, the cellular and circuit mechanisms underlying such recovery remain unclear. Elucidating key neural circuits in post-stroke recovery will be invaluable for translation of neuromodulation for stroke. Here we used optogenetic functional magnetic response imaging (ofMRI) to examine brain-wide circuit dynamics induced by optogenetic stimulation treatment (OST).

Method:
Male mice expressing channelrhodopsin (ChR2) in ipsilesional M1 (iM1) layer V excitatory neurons were used. ofMRI were performed on pre-stroke and post-stroke days (PD) 3, 15 and 29. OST were given daily from PD5-15. Sensorimotor tests were conducted one day prior to each ofMRI session. Mice underwent transient middle cerebral artery occlusion (intraluminal suture model, 30 minutes). Two groups were assigned: stim group (mice with 10 days of OST, n=9) and no stim group (mice without OST, n=9). Activation maps were compared between stim and no stim groups to reveal key brain circuits recovered by OST. The expression of plasticity marker GAP43 was examined using western blot.

Result:
Our results show that 1) Optogenetic excitatory neuronal stimulations in iM1 promotes motor function at PD 14 (P<0.01). 2) At pre-stroke, iM1 stimulations activate expected network including ipsilesional M1, M2, S1, striatum, thalamus, contralateral M1 and cerebellum. 3) At PD3, all mice exhibit a depressed response throughout the brain. 4) At PD15, ipsilesional thalamus and S1 circuits are significantly recovered by OST. Moreover, restoration of thalamic activation is correlated with behavioral recovery in the stim group. 5) At PD15, stimulated mice exhibited higher level of plasticity marker (GAP43) in the ipsilesional thalamus (P<0.05). 6) At PD29, iS1 activation remains stronger in the stim group when compared to no stim group.

Conclusion:
Our findings revealed key circuits underlying stimulation-induced post-stroke recovery. We found that restoration of cortico-thalamic projections is important in stimulation-induced recovery at early phase post-stroke, while sustained strengthening of ipsilesional cortico-cortical connections may be critical in the later phase of recovery.