bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical Research Progress of Vertebral Artery Dominance and Posterior Circulation Ischemic Stroke
Authors: Sun Yan , Shi Yan-Min , Xu Ping
Published: February 2022

Background: The diameters of the vertebral arteries on both sides are usually asymmetrical. Vertebral artery dominance (VAD) and congenital vertebral artery dysplasia are derived from the asymmetry of the vertebral artery diameters on both sides. They are usually regarded as normal congenital vascular variations and have no practical clinical significance. Summary: Recently, several clinical studies have found that VAD is a risk factor for posterior circulation ischemic stroke (PCIS). The existence of VAD is clinically significant for the occurrence of PCIS, and it is recognized by an increasing number of clinicians. Key Messages: This article reviews the frequency and evaluation methods of VAD, its correlation with PCIS, and its mechanism.
CCL17 Aggravates Myocardial Injury by Suppressing Recruitment of Regulatory T Cells
Authors: Feng Guoshuai , Bajpai Geetika , Ma Pan , Koenig Andrew , Bredemeyer Andrea , Lokshina Inessa , Lai Lulu , Förster Irmgard , Leuschner Florian , Kreisel Daniel , Lavine Kory J.
Published: February 2022

Background:

Recent studies have established that CCR2 (C-C chemokine receptor type 2) marks proinflammatory subsets of monocytes, macrophages, and dendritic cells that contribute to adverse left ventricle (LV) remodeling and heart failure progression. Elucidation of the effector mechanisms that mediate adverse effects of CCR2
+
monocytes, macrophages, and dendritic cells will yield important insights into therapeutic strategies to suppress myocardial inflammation.

Methods:

We used mouse models of reperfused myocardial infarction, angiotensin II and phenylephrine infusion, and diphtheria toxin cardiomyocyte ablation to investigate CCL17 (C-C chemokine ligand 17). We used
Ccl17
knockout mice, flow cytometry, RNA sequencing, biochemical assays, cell trafficking studies, and in vivo cell depletion to identify the cell types that generate CCL17, define signaling pathways that controlled its expression, delineate the functional importance of CCL17 in adverse LV remodeling and heart failure progression, and determine the mechanistic basis by which CCL17 exerts its effects.

Results:

We demonstrated that CCL17 is expressed in CCR2
+
macrophages and cluster of differentiation 11b
+
conventional dendritic cells after myocardial infarction, angiotensin II and phenylephrine infusion, and diphtheria toxin cardiomyocyte ablation. We clarified the transcriptional signature of CCL17
+
macrophages and dendritic cells and identified granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling as a key regulator of CCL17 expression through cooperative activation of STAT5 (signal transducer and activator of transcription 5) and canonical NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) signaling.
Ccl17
deletion resulted in reduced LV remodeling, decreased myocardial fibrosis and cardiomyocyte hypertrophy, and improved LV systolic function after myocardial infarction and angiotensin II and phenylephrine infusion. We observed increased abundance of regulatory T cells (Tregs) in the myocardium of injured
Ccl17
knockout mice. CCL17 inhibited Treg recruitment through biased activation of CCR4. CCL17 activated Gq signaling and CCL22 (C-C chemokine ligand 22) activated both Gq and ARRB (β-arrestin) signaling downstream of CCR4. CCL17 competitively inhibited CCL22 stimulated ARRB signaling and Treg migration. We provide evidence that Tregs mediated the protective effects of
Ccl17
deletion on myocardial inflammation and adverse LV remodeling.

Conclusions:

These findings identify CCL17 as a proinflammatory mediator of CCR2
+
macrophages and dendritic cells and suggest that inhibition of CCL17 may serve as an effective strategy to promote Treg recruitment and suppress myocardial inflammation.
Abstract 102: Effect Of Antihypertensives By Class On Cerebral Small Vessel Disease: A Post-hoc Analysis Of SPRINT-MIND
Authors: Goldstein Eric , Wolcott Zoe , Garg Gauri , Navarro Kayla , Delic Alen , Yaghi Shadi , Sederholm Benson H , Prabhakaran Shyam , Wong Ka-ho , de Havenon Adam H
Published: February 2022

Introduction:
Treatment of uncontrolled arterial hypertension reduces the risk of cerebral small vessel disease (CSVD) progression, though it is unclear whether this reduction occurs due to blood pressure control or antihypertensive class-specific pleotropic effects. The goal of this study was to investigate the influence of antihypertensive medication class on accumulation of white matter hyperintensities (WMH), a radiographic marker of CSVD, within a cohort with well-controlled hypertension.

Methods:
Using the SPRINT-MIND dataset, we completed a post-hoc analysis of participants who completed a baseline and 4-year follow-up brain MRI with volumetric WMH data. Antihypertensive medication data were recorded at follow-up visits between the MRIs. A percentage of follow-up time participants were prescribed each of the eleven classes of antihypertensive was then derived. Progression of CSVD was calculated as the difference in WMH volume between two scans and, to address skew, dichotomized into a top tertile (greatest) accumulation and combined middle and bottom tertiles (slowest) accumulation.

Results:
Among 448 individuals included in this study, vascular risk profiles were similar across WMH progression subgroups except age (70.1±7.9 years versus 65.7±7.3 years, p<0.001) and systolic blood pressure (128.3±11.0 mmHg versus 126.2±9.4 mmHg, p=0.039). The high had a mean WMH progression of 4.7±4.3 mL compared with 0.13±1.0 mL for the slowest progressors (p<0.001). Only angiotensin converting enzyme inhibitors (ACE-I) (OR 0.34, 95% CI 0.15-0.75, p=0.008) and dihydropyridine calcium channel blockers (d-CCB) (OR 0.39, 95% CI 0.19-0.81, p=0.012) were independently associated with lower odds of being in the greatest progression grouping.

Conclusions:
Amongst hypertensive participants in the SPRINT-MIND trial, ACE-I and d-CCB antihypertensive medications were associated with significantly lower odds of being in the highest tertile of WMH progression compared with other antihypertensive classes, independent of blood pressure control.
Abstract 126: Cerebral Perfusion Imaging And Posterior Circulation ASPECTS Identify Stroke Patients Who Benefit From Basilar Artery Thrombectomy
Authors: Heit Jeremy J , Bianco Giovanni , Mlynash Michael , Yuen Nicole , Qureshi Abid Y , Hinduja Archana , Dehkharghani Seena , Goldman-Yassen Adam , Hsieh Kevin Li-Chun , Giurgiutiu Dan-victor , Gibson Daniel , Carrera Emmanuel , Alemseged Fana , Faizy Tobias D , Fiehler Jens , Pileggi Marco , Lansberg Maarten G , Campbell Bruce , Albers Gregory W , Cereda Carlo W
Published: February 2022

Introduction:
Acute ischemic stroke due to basilar artery occlusion (AIS-BAO) results in significant morbidity and mortality. Endovascular thrombectomy (ET) has not been shown to improve outcomes in AIS-BAO patients in randomized trials, which may be due to insufficient selection before ET. We determined whether the Critical Area Perfusion Score (CAPS) and posterior circulation ASPECTS (PC-ASPECTS) predict a favorable response to ET.

Methods:
We performed a multicenter retrospective study of AIS-BAO patients with perfusion imaging prior to ET. PC-ASPECTS was determined on NCCT by evaluating the cerebellum (1 point/hemisphere), pons (2 points), midbrain (2 points), thalamus (1 point/hemisphere), and posterior cerebral artery (1 point/hemisphere) territories, and points were subtracted for hypodensity in these regions. CAPS was quantified severe hypoperfusion (Tmax >10s) in cerebellum (1 point/hemisphere), pons (2 points), midbrain and/or thalamus (2 points). The primary outcome was a favorable outcome 90-days after ET (modified Rankin Scale [mRS] 0-3).

Results:
89 patients were included. CAPS (AUC=0.70 [95% CI: 0.59-0.80]; p=0.002) and PC-ASPECTS (AUC=0.63 [95% CI: 0.52-0.75]; p=0.034) both predicted favorable outcomes in a receiver operating curve analysis, but there was no difference between the two (p=0.434). After dichotomization, patients with favorable CAPS (≤3) and PC-ASPECTS (≥7) were more likely to achieve a good functional outcome after successful reperfusion after ET (Figure). However, an unfavorable CAPS (>3) was associated with poor outcomes despite successful thrombectomy in all patients, whereas 22% of patients with unfavorable PC-ASPECTS (<7) still achieved favorable outcomes with reperfusion after ET (Figure).

Conclusions:
CAPS and PC-ASPECTS both identify AIS-BAO patients who are likely to have a favorable clinical response to ET. CAPS, but not PC-ASPECTS, appears to accurately identify a subgroup in whom ET may be futile.
Abstract 131: Multiphase CT Angiography Perfusion Vs. CT Perfusion In Predicting Final Infarction In Acute Stroke Patients
Authors: Souto Maior Neto Luis A , El-Hariri Houssam , Golan Rotem , Mousavi Seyed Hossein , Olajumoke Elebute Ibukun , Duszynski Chris , Sojoudi Alireza , Qiu Wu , Menon Bijoy K
Published: February 2022

Background:
In acute ischemic stroke (AIS), Computed Tomography Perfusion (CT, CTP) is the most widely used technique for determining extent of tissue likely to die even after successful reperfusion. However, CTP results in higher radiation dose to the patient, is affected by motion, and is not widely available. Multiphase CT Angiography (mCTA), by contrast, is a low radiation extension to the ubiquitous CT Angiography workflow. Here, we evaluate StrokeSENS mCTA Perfusion, a software tool that uses mCTA to estimate brain tissue perfusion, and compare it to CTP in its ability to predict final infarction.

Methods:
551 subjects with baseline mCTA, Non-contrast CT (NCCT), and CTP were included. Of these, 480 were part of the development dataset used to derive the mCTA Perfusion algorithm while the remaining 71 were included in the test dataset. T
max
and CBF perfusion maps were generated on CTP using GE CTP-4D Perfusion, and on mCTA using StrokeSENS mCTA Perfusion. Final infarction was manually segmented on 24-48h MRI/NCCT by 2 experts using ITK-SNAP. Voxel values from CTP and mCTA were assessed in their ability to predict final infarction at an individual patient level (AUC calculated for each patient, then averaged across patients) and for the combined patient data (voxels pooled across patients, then one AUC calculated), then compared (two-sided difference test p-value, p).

Results:
At patient level, mCTA Perfusion T
max
AUC was 77.7% (95% c.i.: [74%, 82%]) while CTP T
max
AUC was 74.6% (95% c.i.: [71%, 79%]), p=0.15. mCTA Perfusion CBF AUC was 68.5% (95% c.i.: [65%, 72%]) while CTP CBF AUC was 69.8% (95% c.i.: [67%, 73%]), p=0.43. In combined patient data analysis, mCTA perfusion T
max
AUC was 84.13% while CTP T
max
AUC was 81.36%, p=0. mCTA perfusion CBF AUC was 74.44% while CTP CBF AUC was 72.51%, p=0.

Conclusion:
StrokeSENS mCTA Perfusion software is similar to traditional CT Perfusion in its ability to predict final infarction in patients with acute ischemic stroke.
Abstract 139: Higher Frequency And Odds Of Recurrent/subsequent Stroke Admissions In Young (18-44 Years) Patients With Prior Stroke/transient Ischemic Attack With Versus Without Cannabis Use Disorder: A Nationwide Inpatient Analysis
Authors: Desai Rupak , Went Terry R , Sultan Waleed , Wiltshire Dwayne , Jnaneswaran Geethu , Raju Athul Raj , Asifali Roshna , Mohammad Aamer , Rizvi Bisharah , Jain Akhil
Published: February 2022

Background:
Cannabis use disorder (CUD) is more prevalent in the young population and cannabis use has been linked to an increased risk of first-time stroke or transient ischemic attack (TIA). Prevalence and risk of recurrent stroke in patients with prior stroke/TIA in cannabis users are not clearly established.

Methods:
Using weighted data from the National Inpatient Sample (2015 October-2017 December) and pertinent ICD-10 codes, we identified hospitalizations among young (18-44 years) patients with prior history of stroke/TIA grouped into those with CUD+ and those without (CUD-). We compared the frequency (with disparities based on gender, race, hospital region and median household income) and odds of subsequent/recurrent stroke in young adults (18-44 years) with vs without cannabis use (CUD+ vs. CUD-) and prior history of stroke/TIA.

Results:
Young adult hospitalizations with prior stroke/TIA were 4690 in the CUD+ arm, and 156700 in CUD- arm (median age 37 years in both cohorts). The CUD+ cohort often consisted of males (55.2% vs. 40.2%), African Americans (44.6% vs. 37.2%), and patients with higher rates of concomitant substance abuse, COPD, depression and psychoses, and a lower rate of cardiovascular comorbidities compared to the CUD- cohort (p<0.001)
[Table 1a].
The CUD+ arm had considerably higher rate (6.9 vs 5.4%)
[Table 1b]
and adjusted odds (aOR 1.48, 95 CI 1.28-1.71, p<0.001) of recurrent stroke than CUD- arm
[Table 1c]
. On subgroup comparison, admission among male (7.7% vs. 5.9%), white (6.6% vs. 5.1%), African American (8.0% vs. 5.2%), and admissions in low household income quartile (7.7% vs. 5.5%) patients, Northeast (6.1% vs. 4.4%) and Southern (7.6% vs. 5.7%) region hospitals showed higher rates of recurrent stroke with CUD+ vs. CUD- (p<0.05).

Conclusion:
The frequency and risk (~50% higher) of recurrent stroke were found to be significantly increased with disparities in subgroups among young adults with prior history of stroke/TIA and concomitant CUD.
Abstract 166: Loss Of Endothelial Cell Specific EphA4 Improves Acute Leptomeningeal Collateral Growth Following Ischemic Stroke
Authors: Kaloss Alexandra , Theus Michelle
Published: February 2022

Leptomeningeal anastomoses, or pial collateral vessels, are a major determinant of patient outcome following ischemic stroke. These vessels form in the pia mater of the brain during development and connect distal arterioles of cerebral arteries. Following vascular obstruction, pial collaterals expand through arteriogenesis, an adaptive process that allows for retrograde perfusion into the obstructed artery and its affected tissue. However, acute arteriogenesis following ischemic stroke has been poorly investigated, therefore our research aims to fill this knowledge gap. Our novel pre-clinical murine findings suggest EphA4, a receptor tyrosine kinase, plays a role in restricting arteriogenesis following permanent middle cerebral artery occlusion (pMCAO). To investigate the role of endothelial cell-specific EphA4 in acute arteriogenesis, we employed 3-month old conditional endothelial cell (EC)-specific EphA4 knockout (

EphA4
fl/fl
/Cdh5::Cre
ERT2

; KO) and wild type (

EphA4
fl/fl
;

WT) mice. Compared to WT controls, we find KO mice displayed a significant reduction in infarct volume (24.0±1.8mm
3
vs 14.3±2.5mm
3
; n=9) which correlated with larger ipsilateral pial collateral vessels as early as 4.5-hours (27.31±0.6um vs 32.41±0.8um; n=15) and up to 24-hours post-pMCAO (31.14±0.8um vs 36.7±0.9um; n=15). Additionally, our previous work has indicated that EphA4 may exert its inhibitory function on arteriogenesis by hindering Tie2 signaling. To identify gene expression changes in the collateral vessels and connecting cerebral arteries, the pial surface was carefully isolated from four mice per sample and pooled. Analysis of mRNA expression in the pial surface 24-hours post-pMCAO revealed that WT mice had significantly higher fold change of
angiopoietin-2
(1.4±0.2 vs 0.8± 0.09; n=5) and
Tie1
(5.3±1.8 vs 0.9±0.2; n=5) compared to KO mice, indicating potential inhibition of Tie2 signaling. These findings demonstrate that EC-specific EphA4 negatively regulates collateral growth and inhibition of this receptor could serve as a novel therapeutic strategy for improving collateral response following ischemic stroke.
Abstract 18: Targeting Neutrophil Extracellular Traps Improves Ischemic Stroke Outcomes
Authors: Denorme Frederik , Portier Irina , Cody Mark J , De Araujo Claudia V , Rustad John P , Hoki Chieko , Alexander Matthew D , Grandhi Ramesh , Neal Matthew D , Majersik Jennifer J , Yost Christian C , Campbell Robert
Published: February 2022

Rationale:
Ischemic stroke prompts an inflammatory response which is associated with worse outcomes. Classic anti-inflammatory strategies were unsuccessful in clinical trials, implying other mechanisms contribute to injurious inflammation in stroke. In response to stimuli, neutrophils can release DNA web-like structures called neutrophil extracellular traps (NETs). Recently, a role for NETs in cardiovascular disease has emerged. Here, we studied whether NETs contribute to ischemic stroke outcomes.

Methods:
Markers of NET formation were assessed in brain tissue and plasma from ischemic stroke patients. For murine studies, we used male and female mice that were subjected to transient middle cerebral artery occlusion. Stroke outcomes were assessed 24 hours or 7 days after stroke.

Results:
NETs were found in brain tissue from deceased ischemic stroke patients. Ischemic stroke patients had significantly increased plasma biomarkers of NET formation including citrullinated histone H3 (p<0.0001) and MPO-DNA complexes (p<0.001) compared to matched controls. NET biomarkers positively correlated with worse stroke outcomes at discharge (p<0.05) while they did not correlate with stroke severity at admission. To target NET formation in ischemic stroke, we investigated the therapeutic potential of a recently discovered neonatal NET inhibitory factor (nNIF). nNIF specifically blocks NET formation in human and murine neutrophils without affecting other critical neutrophil functions. Mice prophylactically treated with nNIF had significantly reduced brain and plasma NETs after stroke while cerebral neutrophil recruitment remained unaffected. The reduction in NET formation was associated with significantly reduced neuronal apoptosis and smaller brain infarcts (p<0.0001). Furthermore, nNIF treated mice had improved neurological behavior and motor function, and enhanced 7-day survival after ischemic stroke (p<0.001). Importantly, these results were confirmed in diabetic mice and >18-month-old mice and nNIF was still effective when administered therapeutically, 1 hour after stroke onset.

Conclusions:
Our results support a pathological role for NETs in ischemic stroke and warrant further investigation into nNIF to improve stroke outcomes.
Abstract 41: Functional Outcome Of Patients 85 Years Or Older With Acute Ischemic Stroke Following Endovascular Treatment - A Substudy Of The Hermes Meta-analysis
Authors: McDonough Rosalie V , Ospel Johanna M , Campbell Bruce , Hill Michael D , Saver Jeffrey L , Dippel Diederik W , Demchuk Andrew M , Majoie Charles B , Brown Scott , Mitchell Peter J , Bracard Serge , guillemin francis , Jovin Tudor G , Muir Keith W , White Philip , Goyal Mayank ,   HERMES collaborators
Published: February 2022

Introduction:
Previous studies have reported poor outcomes and high rates of mortality following endovascular therapy (EVT) for ischemic stroke in older patients. However, patients ≥85 years were underrepresented in most randomized trials. Our aim was to study the influence of age on outcome and EVT effect for ischemic stroke in patients aged ≥85 years.

Methods:
Data were from the HERMES collaboration, a meta-analysis of 7 randomized trials that tested the efficacy of EVT. Two multivariable ordinal logistic regression were used to compare the association between EVT and 90-day functional outcome (modified Rankin Scale, primary outcome) in patients ≥85 years old to those who were younger. Secondary outcomes included mortality at 90 days and symptomatic intracranial hemorrhage (sICH) at 24 hours.

Results:
We included 1764 patients in the analysis, of whom 77 (4.4%) were ≥85 years old. While patients ≥85 years had worse outcomes (adjusted odds ratio [aOR] 0.26 (95%CI:0.14-0.48) and higher mortality rates (aOR:3.28, 95%CI:1.54-6.97) compared to those <85 years, a significant benefit of EVT was observed in the ≥85-year-old patient subgroup (common OR:4.20 (95%CI:1.56-11.32, Figure). Patients ≥85 years undergoing EVT had lower rates of mortality than those in the control group (31% vs. 54%, p<0.01). Age ≥85 years was not significantly associated with higher rates of sICH (adjusted cOR:2.3, 95%CI:0.59-8.93).

Conclusion:
Patients ≥85 years old with independent premorbid function more often achieve good functional outcomes when treated with EVT compared to conservative management, with lower rates of mortality and no differences in sICH rates. EVT should therefore not be withheld in this subgroup.
Abstract 46: Effect Of Intravenous Alteplase On Ischemic Stroke Mortality Is Dependent On Stroke Severity
Authors: de Havenon Adam H , Sheth Kevin N , Sultan-qurraie Ali , Tirschwell David L
Published: February 2022

Background:
Intravenous Alteplase (tPA) has a clear benefit on functional outcome after ischemic stroke, but prior studies of its impact on post-stroke mortality have been underpowered, restricted to older Medicare patients, or did not have sufficient representation of patients with more severe stroke.

Methods:
We explored if the interaction between stroke severity (baseline NIHSS) and tPA impacted the risk of mortality after ischemic stroke in two cohorts: 1) National Inpatient Sample 2016-2018 (primary diagnosis ischemic stroke and available NIHSS) and 2) a harmonized cohort of ischemic stroke patients from the NINDS tPA, ALIAS part 2, SHINE, FAST-MAG, IMS-III, POINT, and DEFUSE 3 trials. We fit logistic regression models to the primary outcome of in-hospital death (NIS cohort) or death within 90 days (harmonized cohort), which were adjusted for patient age, sex, race, atrial fibrillation, hypertension, diabetes, and endovascular thrombectomy. For the NIS model, we employed survey design. After regression, we used marginal effects to derive predicted probability.

Results:
We included 391,030 patients in the NIS cohort (mean age 69.7 years, male 50.9%, mean NIHSS 7.0±7.4, 12% NIHSS≥18), of which 15.1% received tPA and 3.8% had in-hospital death. We included 6,950 patients in the harmonized cohort (mean age 66.3 years, 53.9% male, mean NIHSS 7.5±7.9, 23% NIHSS≥18), of which 33.7% received tPA and 9.5% had death by 90 days. In both cohorts, the interaction between NIHSS and tPA was significant (NIS p-value<0.001, harmonized p-value=0.01). As seen in Figure 1, both cohorts had separation at NIHSS of ≥18, at which point tPA began to have a benefit for both in-hospital and 90-day mortality. Nearly identical results were seen when patients who received endovascular therapy were excluded.

Conclusion:
In patients with acute ischemic stroke, tPA administration is associated with a reduction of both in-hospital and 90-day mortality for patients with severe stroke (NIHSS≥18).
Abstract 49: Elevation Of Blood Viscosity In Acute Ischemic Stroke
Authors: Kang Jihoon , Oh Ju Seok , Bae Hee-joon , Kim Beom Joon , Kim Jun Yup , Lee Keon-joo , Han Moon-Ku
Published: February 2022

Objectives:
The blood viscosity would quantify the physiological state of abnormal blood flow and hypercoagulability, which are crucial predisposing factors of ischemic stroke. It investigated whether the viscosity increase in the stroke.

Methods:
It enrolled a series of patients who visited the hospital with any neurologic symptom or sign within 24 h of last well-being. Blood was immediately sampled at the time of hospital arrival as a routine clinical practice along the acute stroke clinical pathway. The viscosity was investigated in a point-of-care test manner using ARS M-200, Rheology Solutions, Korea. It placed the whole blood between the two plates and measured the viscosity by applying a torque of 10 Hz within 5 minutes of taking the blood sample. The primary outcome was an ischemic stroke and other diseases, and the difference in blood viscosity between the two groups was compared.

Results:
In 2021, it enrolled 47 subjects (age, 69.5 ± 12.9 years-old, male, 51.0%) of whose were diagnosed as ischemic stroke (n = 18) and other diseases (n = 29) consisted of hemorrhagic stroke, metabolic encephalopathy, vertigo, seizure, drug intoxication, and peripheral neuropathy. The viscosity of ischemic stroke with 10 Hz torque was significantly higher than those of non-stroke (22.7 ± 7.4 vs. 18.4 ± 7.0 Ps, P = 0.02). In stroke, the viscosity was significantly different between direct visits (25.5 ± 6.6 Ps) and transferred subjects with intravenous fluids (14.3 ± 1.4) (P = 0.003). In the case of hemorrhagic stroke, traumatic hemorrhage presented the highest values (27.1 ± 5.8), which was different from intracerebral hemorrhage (22.1 ± 7.3 Ps, Figure).

Conclusion:
The blood viscosity increased in acute ischemic stroke, which would be used as an auxiliary factor in the emergency setting. Also, it may be warranted the following studies for investigating their prognostic roles.
Abstract 8: Hypoperfusion Lesion And Target Mismatch Prediction In Acute Ischemic Stroke From Baseline Mr Diffusion Imaging Using A 3d Convolutional Neural Network
Authors: Yu Yannan , GONG Enhao , Ouyang Jiahong , Christensen Soren , Scalzo Fabien , Liebeskind David S , Lansberg Maarten G , Albers Greg , Zaharchuk Greg
Published: February 2022

Purpose:
Perfusion imaging assesses target mismatch but requires contrast and processing software. Clinical/diffusion mismatch can miss cases that have target mismatch and could benefit from thrombectomy. We explored whether a neural network can predict hypoperfusion and identify target mismatch from diffusion-weighted imaging (DWI) and clinical information alone.

Methods:
Acute ischemic stroke cases with baseline MR perfusion and DWI were included from two multi-center trials and one registry for model development and a separate randomized trial for external validation. MR perfusion images were processed by RAPID, which segments Tmax lesion (Tmax≥6s) and the ischemic core lesion (apparent diffusion coefficient [ADC]≤ 620). A 3D U-Net was trained using baseline DWI, ADC, NIH stroke scale, and side of stroke as input, and the union of Tmax and ischemic core segmentation as the ground truth. 5-fold cross-validation was performed for model development cohort. Model performance was evaluated by Dice score coefficient (DSC) and volume difference. Sensitivity and specificity of model target mismatch and clinical/diffusion mismatch criteria from the DAWN were compared, using the DEFUSE 3 target mismatch as reference.

Results:
413 patients were included for model development and 46 for external validation. In model development and external validation cohort, the model achieved median DSC of 0.61 (IQR 0.45, 0.71) and 0.62 (IQR 0.53, 0.72); and volume difference of 3 ml (IQR -37, 41) and 7 ml (IQR -24, 32), respectively. Compared to the clinical/diffusion mismatch approach, the model identified target mismatch with a sensitivity of 89.5% vs 49.3%, a specificity of 77.5% vs 89.2% in the model development cohort, and a sensitivity of 95.6% vs 41.3% in external validation cohort.

Conclusion:
A 3D U-Net can predict hypoperfusion lesions from baseline DWI and clinical information, with more sensitive classification of target mismatch than clinical/diffusion mismatch.
Abstract 92: Delirium In-hospital Leads To Poor Short And Long-term Outcomes Among Treated And Non-treated Patients With Acute Ischemic Stroke
Authors: Pan Alan , Agarwal Kathryn , Taffet George E , Jones Stephen L , Potter Thomas , Bako Abdulaziz T , Meeks Jennifer , Tannous Jonika , MCCANE Charles D , Ahmed Wamda , Garg Tanu , GADHIA RAJAN R , Misra Vivek , Volpi John J , Chiu David , Vahidy Farhaan S
Published: February 2022

Background:
Delirium in-hospital (DIH) is common among the critically ill. However, DIH incidence and outcomes are not well characterized among ischemic stroke (IS) patients, particularly those treated with intravenous tissue plasminogen activator (tPA) and / or mechanical thrombectomy (MT).

Methods:
Utilizing data from a healthcare system with standardized delirium screening protocols, DIH was determined by a positive 4AT / CAM-ICU screen or diagnosis codes. IS patients with tPA or MT were flagged and a subset with available 90-day modified Rankin Scale (mRS) were analyzed for shifts in mRS scores associated with DIH, via ordinal logistic regression models adjusted for age, stroke severity, tPA or MT, Charlson Comorbidity Index [CCI], prior stroke and sepsis / infections. Common odds ratios (OR) and 95% confidence intervals (CI) are reported.

Results:
Between May 2016 and June 2021, IS was the primary discharge diagnosis in 12,415 encounters (10,878 unique patients). DIH was documented in 41.6% of IS encounters, compared to 20.0% of non-IS encounters. Stroke-DIH patients (vs no-DIH Stroke) were older (median: 75 vs 65 years), more frequently female (53.3% vs 48.7%), with higher comorbidity burden (median CCI: 7 vs 5), longer hospital stays (median: 6 vs 3 days), higher in-hospital mortality (3.1% vs 0.5%), and fewer home discharges (36.2% vs 75.2%). Among a sub-cohort of 2,785 IS patients with 90-day mRS, fully adjusted model indicated lower mRS (OR, CI: 0.48, 0.41-0.57) for those with tPA or MT, and worse outcomes for DIH patients (OR, CI: 2.70, 2.26-3.23). Among 948 treated IS patients, DIH remained a significant risk for worse outcomes (OR, CI: 2.54, 1.89-3.43).

Conclusion:
Delirium was twice as common in IS patients and was a negative prognostic indicator of short and long-term outcomes among non-treated and treated IS patients. Active screening and management of DIH is critically important to improve stroke outcomes.
Abstract 96: CompLement C5 Antibodies For Decreasing Brain Injury After Aneurysmal Subarachnoid Hemorrhage (CLASH): A Randomized Controlled Phase II Clinical Trial
Authors: Koopman Inez , Tack Reinier W , Rinkel Gabriel J , Vergouwen Mervyn D ,   CLASH study group
Published: February 2022

Introduction:
The inflammatory response after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischemia, and poor functional outcome. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. We investigated the pharmacodynamic efficacy and safety of eculizumab (a complement C5 antibody) in aSAH patients.

Methods:
We conducted a randomized, controlled, open-label, phase II clinical trial with blinded outcome assessment in the Netherlands. Patients were randomized (1:1) to receive eculizumab plus standard care or to standard care alone. Eculizumab (1200 mg) was administered intravenously < 12 h, on day 3 and on day 7 after ictus. Patients in the intervention group received prophylactic antibiotics for 4 weeks and prophylactic antifungal therapy if the patient had a central line or an external ventricular shunt and a positive fungal or yeast culture. The primary outcome was C5a concentration in the cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes included the occurrence of adverse events, eculizumab concentration and inflammatory parameters in the blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical and cognitive outcomes. We aimed to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the comparator group.

Results:
A total of 31 patients have been included, of which 26 with CSF samples.

Conclusions:
Final results will be presented at the conference.

Trial registration:
Netherlands Trial Register: NTR6752. European Clinical Trials Database (EudraCT): 2017-004307-51.
Abstract NS8: Nurses Need Education On Women's Unique Stroke Symptoms
Authors: Colsch Renee
Published: February 2022

Background:
Stroke remains the third-leading cause of death and a major cause of disability in women. After a stroke, women have a 59% disability rate compared to 26% for men in the acute phase. Men and women share common stroke symptoms. However, women can also experience “unique” “atypical,” or “nontraditional” stroke symptoms. Early recognition of stroke is crucial to better outcomes, but despite the fact that nurses play a crucial role in identifying stroke symptoms and activating care early, information is lacking on nurse’s knowledge in recognizing stroke symptoms in women.

Purpose:
To examine nurse’s knowledge and confidence level in recognizing common and unique stroke symptoms in women.

Methods:
In this quantitative study, nurses were recruited via targeted social media platforms to complete an online survey about women and stroke. Nurses self-declared that they met eligibility criteria. A nurse was defined as an individual who holds a license, is legally permitted to practice, and holds the title of Registered Nurse, Advanced Practice Nurse (masters or doctorate), or Licensed Practical Nurse. Data were analyzed using descriptive statistics, independent
t
-tests, and one-way ANOVA.

Results:
129 nurses completed the survey over four months. Nurses were 86% women with a mean age of 42 years, and 55% held advanced degrees. Over 80% identified the common stroke symptoms of stroke, and over 70% identified the additional stroke symptoms. However, less than 25% could identify unique stroke symptoms of women, including difficulty breathing or shortness of breath (7%), hallucination (11%). A majority of the nurses (76%) lacked the confidence to recognize stroke symptoms in women. Lower scores for common stroke symptom knowledge (
p
=0.01), confidence (
p
=0.01), and unique stroke symptoms in women confidence scores (
p
=0.05) were observed in nurses with < 20 years’ experience.

Conclusions:
Nurses lacked knowledge and confidence in correctly identifying unique stroke symptoms in women with nurses who had fewer years of professional experience fairing worse. Education targeted at nurses should include strategies to enhance their knowledge and confidence level in recognizing stroke symptoms unique to women.
Abstract TMP30: Disparities In Telemedicine Use Among Stroke Survivors: The Experience Of Three Tertiary Stroke Centers
Authors: Naqvi Imama A , Cohen Audrey Sarah , Kim Youngran , Denny Mary C , Harris Jennifer , Leite Ryan , Sadowsky Dylan J , Adegboye Comfort , Bicher Nathan , Okpala Nnedinma , Okpala Munachi N , Sharrief Anjail Z
Published: February 2022

Introduction:
In response to the COVID-19 pandemic, outpatient stroke care delivery was rapidly transformed to telemedicine (TM) care through video (VTM) and telephone (TPH) visits around the world. We sought to evaluate the sociodemographic differences in TM use among stroke survivors.

Methods:
We conducted a retrospective chart review of stroke survivors evaluated at three tertiary stroke center clinics in the early period of the pandemic, 3/16/2020 till 7/31/2020. We compared the use of TM by demographics. The association between the use of TM and race/ethnicity was measured using the relative risk (RR) from a modified Poisson regression model adjusting for age, sex, insurance status, stroke type, visit type, and site.

Results:
A total of 2,024 individuals were included from UTHealth (n=878), MedStar Georgetown (n=269), and Columbia (n=877). Median age was 64 [IQR 52-74] and 53% were female. About half the patients had private insurance, 36% had Medicare and 15% had Medicaid. Two-thirds of the visits were established patients. TM accounted for 90% and the use of TM over office visits was primarily associated with site, not patients’ characteristics. Among TM users, older age, non-White, and Medicaid were associated with lower VTM compared to TPH use. Black (aRR 0.90, 95% CI 0.85-0.95, p<0.001) and Hispanic patients (aRR 0.91, 95% CI 0.86 - 0.97, p=0.005) had 10% lower VTM use while Asian patients (aRR 0.98, 95% CI 0.90 - 1.06, p=0.56) had similar VTM use compared to White patients (Figure).

Conclusions:
In our diverse cohort, we found differences in TM visit type by race and insurance, with overall higher utilization among established patients. These findings suggest disparities in VTM access across different stroke populations. As VTM becomes an integral part of outpatient practice, steps to ensure equitable access are essential.
Abstract TMP32: Modeling Optimal Patient Transport In A Stroke Network Capable Of Telerobotic Endovascular Therapy
Authors: Beaman Charles , Holodinsky Jessalyn K , Goyal Mayank , Hill Michael D , Saver Jeffrey L , Kamal Noreen
Published: February 2022

Introduction:
Endovascular therapy (EVT) is the standard-of-care for large vessel occlusion stroke; yet, a substantial portion of the population lacks timely access to the treatment. Telerobotics has the potential to expand current stroke networks by offering remote EVT to more rural populations.

Methods:
We geospatially mapped all existing hospitals in California and then assessed hypothetical scenarios in which primary stroke centers between 50 and 100 miles from an existing EVT center offered remote EVT via robotics. Using an existing conditional probability model, we determined the transport scenarios (drip and ship, direct to robotic EVT center, or direct to conventional EVT center) resulting in best patient outcomes in diverse geographies across the state. Timing and the probability of receiving EVT (used as a surrogate for the probability of receiving successful reperfusion) were varied at robotic centers to assess impact on best predicted transport options.

Results:
10 hospitals were converted to robotic EVT centers, resulting in enhanced patient access to timely EVT by routing patients in a rural catchment area of 113,063 km
2
directly to robotic EVT centers (figure). Slowing the door to arterial access time at the robotic centers by 30 minutes had a minor impact on optimized service arrangements (reducing the robotic catchment area to 110,555 km
2
). However, decreasing the probability of receiving EVT at the robotic centers by 0.10 had a substantial impact, reducing the robotic EVT catchment area to 35,061 km
2
and nearly doubling the drip and ship catchment area.

Discussion:
Telerobotic EVT has the potential to enhance therapy for stroke patients outside of major urban centers. We found that the reduced probability of receiving EVT had a greater impact on the optimized size of robotic EVT center catchment areas compared to longer door to arterial access times. This modeling analysis can inform system planning for the potential advent of remote robotic EVT care.
Abstract TMP62: Carotid Web Stenting Is Comparable To Atherosclerotic Stenting With Lower Procedural Risk
Authors: Osehobo Ehizele M , Nogueira Raul G , Karunamuni Nilushi R , Koneru Sitara , Landzberg David , Alshaer Qasem , Al-bayati Alhamza R , Haussen Diogo C
Published: February 2022

Introduction:
Carotid Web (CaW) is an underrecognized etiology for ischemic stroke. This entity has been shown to be amenable to endovascular stenting, similar to carotid atherosclerotic stenosis (CAS). We aimed to assess procedural characteristics of stenting for CaW as compared to CAS.

Methods:
We retrospectively analyzed a cohort of patients at a single comprehensive stroke center from October 2014 to March 2021 who had undergone endovascular stent placement for symptomatic CAS or CaW. Patients who received other intervention (e.g. thrombectomy, aneurysm repair) on the same day as stent placement were excluded. Baseline patient characteristics, procedural data, periprocedural complications, and follow-up statistics were analyzed.

Results:
In total, 105 patients underwent stent placement status post ischemic stroke or transient ischemic attack; 79 patients had CAS and 26 patients had CaW. Patients with CAS were older on average (CAS 63 vs CAS 53.5 years,
p
<
0.001
) and less likely to be female (OR 0.116; 95% CI 0.041 to 0.326,
p
<0.001). CAS patients were more likely to have vascular risk factors such as hypertension, hyperlipidemia, and Diabetes (
Table
). Radiation, need for angioplasty, and filter time were significantly lower in CaW procedures. No significant difference was found between the two pathologies in periprocedural complications such as hypotension, need for vasopressors, or bradycardia. However, post-procedural restenosis only occurred in CAS stents.

Conclusion:
Stenting for CaW is comparable to stenting for CAS in terms of vasovagal side effects, but associated with lower filter times, lower radiation dose, lower need for angioplasty, and lower rates of restenosis.
Abstract TMP68: Underlying Intracranial Atherosclerosis Disease Is Associated With Worse Outcome In Acute Large Vessel Occlusion Undergoing Endovascular Therapy
Authors: Thind Sonam , mansour ali , Mendelson Scott J , Brorson James R , McKoy Cedric , Coleman Elisheva , Prabhakaran Shyam , Kass-Hout Tareq
Published: February 2022

Introduction:
Acute large vessel occlusion (LVO) can be secondary to thromboembolism or underlying intracranial atherosclerotic disease (ICAD). Data on the management of LVO due to underlying ICAD are scarce.

Hypothesis:
We hypothesized that patients with ICAD would have worse clinical outcomes following mechanical thrombectomy (MT) than those without ICAD.

Methods:
We performed a retrospective analysis of consecutive patients who underwent MT for LVO in a large academic comprehensive stroke center between 01/2018 and 05/2021. Presence of underlying ICAD at the site of LVO was determined by the treating interventionalist. We compared outcomes including in-hospital mortality and 90-day modified Rankin Scale (mRS) between those with and without underlying ICAD, adjusting for relevant covariates using logistic regression.

Results:
Among 195 patients (mean age 67.4+15.1 years, 56.9% female, 81% black, median NIHSS score 15), underlying ICAD was present in 39 (20.0%). Stent-retrievers were used 196 patients with only 3 having rescue stent placement. There were no significant differences in baseline factors amongst the two groups except diabetes was more common (69.2% vs. 49.7%, p=0.028) and intravenous thrombolysis provided less often (17.9% vs. 36.5%, p=0.027) in those with ICAD. TICI 2B or higher was achieved in 82.1% of ICAD compared with 94.3% of non-ICAD patients (p=0.012). Mortality was more common (50.0% vs. 30.8%, p=0.025) and good functional outcome (mRS 0-2) at 90 days was less common (10.8% vs. 30.0%, p=0.002) in the ICAD group. Adjusting for age, diabetes, intravenous thrombolysis, baseline NIHSS score, and final TICI score, underlying ICAD was an independent predictor of mRS 0-2 at 90 days (OR 4.5, 95% CI 1.4-14.2, p=0.010).

Conclusion:
Underlying ICAD is associated with 4.5-fold increase in poor functional outcome in patients with LVO undergoing traditional MT. Further research is needed to understand factors associated with poor outcomes investigate alternative interventional approaches and medical management in this high-risk population.
Abstract TMP85: Hyperacute Pediatric NIH Stroke Scale Does Not Predict 3-month Outcome In Children
Authors: Galardi Maria M M , Barry Dwight , Guilliams Kristin , Amlie-lefond Catherine ,   Thrombolysis in Pediatric Stroke (TIPSTER) Investigators
Published: February 2022

Background:
The assumption of severity of initial stroke symptoms predicting long-term outcomes is foundational to deciding whether to give hyperacute therapies. The relationship is well-established in adult stroke, however, children often have additional symptoms at presentation, such as altered mental status, which may influence the pediatric NIH stroke scale (PedNIHSS). Prior preliminary work found that PedNIHSS obtained at a median of 28 hours from symptom onset was associated with long-term outcomes. We therefore sought to establish whether the initial hyperacute PedNIHSS, obtained within a possible hyperacute treatment window, correlates with long-term outcomes.

Hypothesis:
We hypothesized that hyperacute PedNIHSS would correlate with pediatric stroke outcome measure (PSOM) at 3 months.

Methods:
Multicenter data was prospectively collected and retrospectively reviewed. The hyperacute PedNIHSS was defined as PedNIHSS obtained within 24 hours of symptom onset and time last seen well (TLSW). Data were analyzed using Spearman’s correlation, quantile regression, and ordinal logistic regression.

Results:
Among a total of 79 children, mean age was 12.7 years and 51% were female. PedNIHSS was obtained 0 to 23.6 hours, median 2.0 hours from symptom onset and/or TLSW. Median PedNIHSS score was 13 [IQR 9-17]. 93% received hyperacute therapies. Three children died within first 3 months. Median PSOM was 1 [IQR 0.5-2.5] at 3 months. Hyperacute NIHSS and PSOM at 3 months were both available in a total of 57 patients. There was no correlation between hyperacute NIHSS and PSOM at 3 months (r=0.27, n=57) (
Figure
).

Conclusion:
Hyperacute PedNIHSS did not correlate with outcomes in our data. Further work is needed to understand factors influencing initial PedNIHSS and acute management that may confound the relationship between initial assessment and long-term outcome in children with acute ischemic stroke.
Abstract TP125: Interpreter Requirements Needed For Tpa Evaluations And Resulting Performance (INTERP)
Authors: Bu Julia , Meyer Dawn M , Shifflett Ben , Meyer Brett C
Published: February 2022

Introduction:
Acute ischemic stroke (AIS) patients requiring interpreter services during an acute stroke code can experience care delays. Prior research has shown no differences in door-to-needle times in non-English fluent patients. The purpose of this study was to examine the influence of interpreter service needs (IS) on time metrics of tPA administration.

Methods:
We retrospectively reviewed prospectively collected data from our Comprehensive Stroke Center database (1/2011-4/1/2021) and EMR. Subjects with a discharge diagnosis of AIS for whom a “stroke code” was activated were included; in-house strokes were excluded. Baseline characteristics, frequency of tPA, tPA exclusions, NIHSS, and tPA time metrics were compared between patients who did or did not require IS. Analyses utilized ANOVA, t Test, or Pearson’s Chi-squared test as appropriate.

Results:
Of 1,043 patients with AIS, 41 had a documented need for IS. tPA was administered in 9 IS and 322 non-IS patients. In IS patients, there were no differences in baseline characteristics between those who received tPA and those who did not. In patients who received tPA, there was a larger amount of Hispanic ethnicity (p<0.01) and hyperlipidemia (p=0.02) in patients requiring IS. There were no tPA rate differences between those that did not and did require IS (22% vs 32%; p=0.22). Patients excluded from tPA due to being out of the window were more likely to have required IS (35% vs 59%; p = 0.003). Onset to arrival (p = 0.89), arrival to treatment decision (p = 0.85), door to needle (p=0.41), and onset to treatment (0.41) were not different in IS patients. Median NIHSS was not different overall (p=0.70) or in tPA patients (p=0.36).

Conclusions:
This study found no significant difference in frequency or time metrics of tPA administration in AIS patients requiring interpreter services during an acute stroke code. If a patient required an interpreter, they were more likely to be excluded from tPA on the basis of time. We hypothesize this is due to increased time required to obtain relevant history or exam data or small sample size. Further work is planned in larger data sets to ensure resource availability to patients who are in need of interpreter services.