bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 119: Initiating Oral Anticoagulation 4 to 14 Days After a Cardioembolic Stroke is Not Associated With a Reduction in Ischemic or Hemorrhagic Events: The IAC Multicenter Cohort
Authors: Yaghi Shadi , Trivedi Tushar , Giles James , Liu Angela , Nagy Muhammad , Kaushal Ashutosh , Azher Idrees , Mac Grory Brian , Fakhri Hiba , Brown Espaillat Kiersten , Asad Syed Daniyal , Pasupuleti Hemanth , Martin Heather , Tan Jose , Veerasamy Manivannan , Liberman Ava , Esenwa Charles , Cheng Natalie , Moncrieffe Khadean , Moeini-Naghani Iman , Siddu Mithilesh , Scher Erica , Leon Guerrero Christopher , Khan Muhib , Nouh Amre , Mistry Eva , Henninger Nils , Keyrouz Salah , Furie Karen
Published: June 2021

Background/Aims:
Guidelines suggest initiating anticoagulation after cardioembolic stroke within 4-14 days from the index event. Data supporting this suggestion did not account for important factors such as infarct burden or early hemorrhagic transformation.

Methods:
We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with an acute cardioembolic stroke in the setting of atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days) and the primary outcome was the composite endpoint of recurrent stroke/TIA/systemic embolism, symptomatic intracerebral hemorrhage (sICH), or major extracranial hemorrhage (ECH) within 90 days.

Results:
We enrolled 2090 patients from 8 comprehensive centers in the United States, 1325 met the inclusion criteria (362 were excluded due to non-composite endpoint related death within 90 days, 145 lost to follow up, and 258 were not started on oral anticoagulation or the timing was not reported). Anticoagulation (875 DOAC, 404 Warfarin) was initiated in 0-3 days in 49.7%, 4-14 days in 40.4%, and >14 days in 9.9%. The combined endpoint occurred in 10.7% (142) (98 ischemic events, 21 sICH, and 30 ECH) and did not differ between the three groups: 0-3 days (11.9%), 4-14 days (9.9%), >14 days (9.9%), p=0.525. After adjusting for confounders (such as infarct volume, bridging, CHADS2-Vasc, cardiac thrombus, and hemorrhage on 24-hr imaging), oral anticoagulation timing in the 4-14 day period (vs. >14) was not associated with a reduction in ischemic events (adjusted OR 0.74, p=0.438) and oral anticoagulation timing 4-14 days (vs. 0-3) was not associated with a reduction in sICH (OR 1.28, p=0.638). Factors associated with sICH were bridging (OR 5.36, p=0.001) and hemorrhage on 24-hr imaging (OR 7.26, p<0.001) whereas for ischemic events were warfarin treatment (OR 1.66 95%, p = 0.030) and prior stroke (OR 1.81, p=0.013).

Conclusion:
In this multicenter real world cohort, the recommended (4-14 days) timeframe to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required determine the optimal timing of anticoagulation initiation.
Abstract 12: An Evaluation of Functional Outcome at 1 Year of Poor Prognosis Patients in Mistie-III
Authors: Ostapkovich Noeleen , Avadhani Radhika , Carhuapoma Lourdes , Thompson Richard E , Lane Karen , McBee Nichol , Ziai Wendy , Awad Issam , Hanley Dan
Published: June 2021

Introduction:
Clinical factors impacting prognosis following Intracerebral Hemorrhage (ICH) have been well described in the literature, with “poor” prognosis often leading to withdrawing life sustaining treatments (WoLST). The MISTIE-III trial data provides an opportunity to review 12 month outcome of “poor" prognosis subjects.

Methods:
In order to evaluate functional recovery of ICH survivors compared with patients who had WoLST we used a severity index (SI) score for predicting good functional recovery 1 year following ICH. The SI used 6 clinical univariate variables from the MISTIE-III analysis (age
>
67, Glasgow Coma Score [GCS]
<
8, deep ICH location, stability ICH volume
>
45mL, stability intraventricular hemorrhage (IVH) volume>0.4mL) and
>
3 comorbidities (hypertension, hyperlipidemia, cardiovascular disease, and end-stage renal disease). Based on the SI scores for subjects who had WoLST, a matched cohort of survivors with “poor" prognosis (mRS 4-5) were tracked for functional recovery for 12 months.

Results:
Of the participants enrolled in MSITIE-III, 61 had WoLST. Of the non-WoLST ICH survivors, 16 progressed to death during the acute period. Another 48 had died prior to the 1 year (D365) follow up. At the 30 Day (D30) evaluation, there were 263 ICH survivors with “poor" prognosis SI scores having a mRS of 4 or 5 and 94% were still in a treatment facility. By D365, 47% of the “poor prognosis” patients had improved to mRS 0-3 (good outcome) with 98% living at home. Of the remaining, 36% had a mRS of 4 (moderately severe disability) with 64% living at home, and 17% had a mRS of 5 (severe disability) with 31% living at home.

Conclusion:
For family members of patients sustaining an ICH where clinical factors indicate a “poor" prognosis, the decision to continue or withdraw life sustaining treatment is difficult. Our data shows that ICH patients with clinical factors that are assumed to indicate “poor" prognosis for recovery can, when given time, achieve a favorable outcome.
Abstract 128: RNA-seq Based Non-Invasive Endovascular Biopsy of Brain Arteriovenous Malformations
Authors: Winkler Ethan , McCoy David , Sun Zhengda , Cooke Daniel
Published: June 2021

Introduction:
To-date, there is no accurate means to identify which bAVMs will bleed and treatment remains controversial.

Hypothesis:
We developed an endovascular biopsy (EB) technique to isolate endothelial cells (ECs) from bAVMs in patients. We hypothesized this technique would allow RNA-seq analysis of relevant bAVM-related molecular pathways.

Methods:
EB was performed during angiography for bAVM patients undergoing resection. Cells were obtained from a bAVM juxta-nidal feeding artery and iliac artery (control) with a detachable coil and 0.035 inch wire. ECs were isolated with fluorescence assisted cell sorting (FACS). bAVM tissue was obtained from surgery, dissociated and underwent FACS sorting. Total RNA extraction and library preparation was performed, and samples sequenced on an Illumina HiSeq 4000 sequencer. Reads were aligned with Kallisto, and differentially expressed genes identified between bAVM and control with Sleuth using likelihood ratio tests. Correlations between EB and resected tissues were calculated with Pearson correlation coefficients. Principle Component Analysis (PCA) was used to assess for cell clustering.

Results:
EB was performed in 4 patients without complication or adverse event. PCA showed separation of bAVM ECs from controls. Analysis demonstrated 106 differentially expressed genes (FDR p ≤ 0.05). KEGG pathway analysis on these genes revealed enrichment in bAVM-related RAS/MAPK cell signaling functionally related to trophic factor, chemokine and gap junction signaling pathways. Detected genes were strongly correlated between EB and ECs isolated from resected tissues (R
2
= 0.77 for artery, nidus, and vein tissue). Results shown in
Figure 1
.

Conclusions:
EB is a safe technique to permit non-invasive sequencing of bAVMs. These results implicate dysregulated KRAS/MAPK signaling in adult bAVMs. Whether this technique will allow for better natural history prediction or targeted medical therapies requires future study.
Abstract 134: Digital-AF II: Impact of Smartphone-Based Atrial Fibrillation Screening in the General Population for Primary Stroke Prevention
Authors: Proesmans Tine , Vanacker Peter , Verbrugge Frederik H , Vandevoort Pieter , Ruttgers Matthieu , Vanhooren Geert , Nuyens Dieter
Published: June 2021

Background:
Opportunistic AF screening for primary stroke prevention is recommended in patients aged above 65 based on stroke risk models. Logistics hamper uniform screening with 12-lead ECG. Novel technologies, e.g. photoplethysmography-based (PPG) apps, may overcome this, providing readily available screening at low cost. We assessed the feasibility of smartphone screening and the impact on subsequent clinical care.

Methods:
A media campaign educated on AF, recruited subjects, and gave access to a PPG-based app to assess the heart rhythm. Subjects were instructed to measure twice daily for 8 days. An algorithm classified the traces as regular, possible AF, non-AF irregularity, or insufficient quality. PPGs of possible irregularities or AF were reviewed by medical technicians and cardiologists. If AF was confirmed, a physician visit was recommended. Questionnaires collected data on clinical care.

Results:
In 2 weeks, 62,821 subjects onboarded, resulting in 588,336 60-second PPG traces. The screened population was 49±15 years, 58% was male. In 791 subjects (1.3%), AF was diagnosed by the algorithm and offline confirmed. This group was older (62±11 years, p<0.001), more frequently male (76%, p<0.001) and had a higher CHA2DS2-VASc score (1.00±1.00 vs 2.00±2.00, p<0.001). The proportion with CHA2DS2-VASc ≥ 1 is 81.3% for the AF cohort vs 64.3% in non-AF cohort. The AF yield increased from 0.52% with 1 recording to 1.84% after 8 days. Of the AF patients, 335 (42%) were known, 373 (47%) newly identified, and 83 (11%) did not give this information. A physician was consulted by 138 (17%) newly identified patients, findings were confirmed in 71 (9%), 46 (6%) received antithrombotic therapy.

Conclusion:
This digital screening, targeting the general population and using only smartphones, demonstrates the feasibility to collect data in a scalable and low-cost way. Next to single timepoint ECG, twice-daily PPG may detect a significant number of asymptomatic AF patients.
Abstract 138: Angiotensin Converting Enzyme (ACE) Inhibition Reverses Vasoconstriction and Impaired Dilation of Pial Collaterals During Chronic Hypertension
Authors: Li Zhaojin , Lindner Devon , Cipolla Marilyn J
Published: June 2021

Introduction:
Leptomeningeal anastomoses (LMAs) are pial collaterals that perfuse the penumbra and are important for stroke outcome. In the current study, we investigated mechanisms by which hypertension causes LMA vasoconstriction that is known to limit the amount of salvageable tissue when stroke occurs during chronic hypertension. We hypothesized that increased vasoreactivity of LMAs from hypertensive rats is angiotensin II (Ang II)-dependent.

Methods:
Spontaneously hypertensive rats (SHRs, n=8/group) were treated with the ACE inhibitor captopril, hydralazine to lower blood pressure (BP) independent of AngII, or vehicle for 5 weeks in drinking water. A group of normotensive Wistar rats (n=8) had regular drinking water served as controls. BP was measured twice weekly by tail cuff. LMAs were isolated and studied in pressurized conditions. Vasoactivity of LMAs, including myogenic responses, reactivity to the Rho-kinase inhibitor Y-27632 and nitric oxide (NO) were measured.

Results:
Both captopril and hydralazine lowered BP in SHRs similar to Wistar rats. LMAs from untreated SHRs had increased myogenic tone vs. Wistar that was normalized by captopril but not hydralazine (Fig. 1A). LMAs from all groups constricted similarly to NO synthase inhibition; however, the vasodilatory response of LMAs to the NO donor sodium nitroprusside, was impaired in SHRs vs. Wistar rats that was restored by captopril and not hydralazine (Fig. 1B). Maximum vasodilatory response of LMAs to Y-27632 was impaired in SHRs compared to Wistar rats (28±3% vs. 81±4%, p<0.01) that was restored by captopril (84±5%) and partially by hydralazine (59±4%) treatment.

Conclusions:
ACE inhibition during chronic hypertension reversed vascular dysfunction and hyperconstriction of LMAs, an effect that could improve stroke outcome by increasing collateral perfusion. In addition, lowering BP alone without inhibition of Ang II, may not provide the same protective effect on pial collaterals.
Abstract 139: Promoter Methylation Changes in
ALOX12, AIRE1, and NETO1
: Novel Epigenetic Markers for Atherosclerosis
Authors: Kim Jee Yeon , Choi Bong-Gen , Jelinek Jaroslav , Kim Dae Hyun , Cho Kwangjo , Rha Seo Hee , Lee Young Ho , Kim Geun-Eun , Kwon Sun U. , Hwang Junha , Cha Jae Kwan , Issa Jean-Pierre J. , Kim Jei
Published: June 2021

Background and Objective:
We aimed to identify and validate specific genes developing changes in promoter methylation in atherosclerotic plaques.

Methods:
We initially profiled DNA methylation signatures via a high-throughput sequencing platform from 5 carotid endarterectomy (CEA) plaques to identify genes with altered promoter methylation. The significances of the identified gene-specific promoter methylations were validated by the comparison between 1) plaques and non-plaque intima of the common carotid artery harvested from 20 cadavers, 2) cellular components composing atherosclerosis including plaques and buffy coats of blood of 27 CEA patients, 5 human umbilical vein endothelial cells (HUVEC), 2 human aortic endothelial (HAEC) and 2 smooth muscle (HASMC) cell lines, and, 3) monocytes, T- and B-cell circulating in blood of 19 ischemic stroke patients. Finally, the localization pattern the genes was compared by the inflammatory cell types infiltrated into atherosclerotic plaque and non-plaque intima using immunofluorescence stain.

Results:
Upon the profiling, five genes (
AIRE1
,
ALOX12
,
FANK1
,
NETO1
, and
SERHL2
) displayed changes in promoter methylation. Of these,
AIRE1
,
ALOX12, and NETO1
displayed higher methylation in plaques than in non-plaque intima, but lower than buffy coat of blood. In vascular cells,
AIRE1
and
NETO1
methylation was lower in HUVEC, HAEC and HASMC, but,
ALOX12
methylation was higher in HUVEC and HAEC, but, lower in HASMC than CEA plaques. Of inflammatory cells, methylation of the three genes was significantly lower in monocytes than T- and B-cells. On immunofluorescence statin for ALOX12, CD14(+)-monocytes was 3 times more frequent than CD4(+)-T-cell of total ALOX12-stained cells in plaques than non-plaque intima.

Conclusions:
The present study profiled and validated the promoter methylation changes of
AIRE1
,
ALOX12,
and
NETO1
as novel epigenetic markers related with atherosclerosis. In particular, epigenetic augmentation of the 3 genes occurred in monocytes of the cellular components composing atherosclerotic plaques.
Abstract 141: Artificial Intelligence to Improve the Detection and Triage of Cerebral Aneurysms
Authors: Mendes Pereira Vitor , Donner Yoni , Levi Gil , Cancelliere Nicole , Wasserman Erez , Perry da Câmara Catarina , Mirella Silva Lobato Mendes Karla , Nicholson Patrick , Golan David , Krings Timo , Nogueira Raul
Published: June 2021

Cerebral Aneurysms (CAs) may occur in 5-10% of the population. They can be often missed because they require a very methodological diagnostic approach. We developed an algorithm using artificial intelligence to assist and supervise and detect CAs.

Methods:
We developed an automated algorithm to detect CAs. The algorithm is based on 3D convolutional neural network modeled as a U-net. We included all saccular CAs from 2014 to 2016 from a single center. Normal and pathological datasets were prepared and annotated in 3D using an in-house developed platform. To assess the accuracy and to optimize the model, we assessed preliminary results using a validation dataset. After the algorithm was trained, a dataset was used to evaluate final IA detection and aneurysm measurements. The accuracy of the algorithm was derived using ROC curves and Pearson correlation tests.

Results:
We used 528 CTAs with 674 aneurysms at the following locations: ACA (3%), ACA/ACOM (26.1%), ICA/MCA (26.3%), MCA (29.4%), PCA/PCOM (2.3%), Basilar (6.6%), Vertebral (2.3%) and other (3.7%). Training datasets consisted of 189 CA scans. We plotted ROC curves and achieved an AUC of 0.85 for unruptured and 0.88 for ruptured CAs. We improved the model performance by increasing the training dataset employing various methods of data augmentation to leverage the data to its fullest. The final model tested was performed in 528 CTAs using 5-fold cross-validation and an additional set of 2400 normal CTAs. There was a significant improvement compared to the initial assessment, with an AUC of 0.93 for unruptured and 0.94 for ruptured. The algorithm detected larger aneurysms more accurately, reaching an AUC of 0.97 and a 91.5% specificity at 90% sensitivity for aneurysms larger than 7mm. Also, the algorithm accurately detected CAs in the following locations: basilar(AUC of 0.97) and MCA/ACOM (AUC of 0.94). The volume measurement (mm3) by the model compared to the annotated one achieved a Pearson correlation of 99.36.

Conclusion:
The Viz.ai aneurysm algorithm was able to detect and measure ruptured and unruptured CAs in consecutive CTAs. The model has demonstrated that a deep learning AI algorithm can achieve clinically useful levels of accuracy for clinical decision support.
Abstract 143: Increased Contrast Enhancement of the Parent Vessel of Unruptured Intracranial Aneurysms in 7T Magnetic Resonance Imaging
Authors: Roa Jorge A , Zanaty Mario , Osorno-Cruz Carlos , Pazour Avery , Ishii Daizo , Ortega-Gutierrez Santiago , Magnotta Vincent A , Hasan David M , Samaniego Edgar A
Published: June 2021

Background:
Aneurysm formation and growth might be explained by a local inflammatory/vasculopathic process that debilitates the wall of the parent artery. Recently, the presence of aneurysm enhancement on high-resolution vessel wall imaging (HR-VWI) has been proposed as a surrogate for vessel wall inflammation. However, no studies have correlated circumferential aneurysm wall enhancement (CAWE) and aneurysm-to-pituitary enhancement ratio (CR
stalk
) on HR-VWI with parent vessel enhancement (PVE) and reference vessel enhancement (RVE).

Methods:
Patients with unruptured intracranial aneurysms prospectively underwent HR-VWI using 7T MRI. CAWE, CR
stalk
, PVE and RVE were objectively analyzed by measuring signal intensity in T1 post-contrast sequences using manual 3D co-registration and segmentation of the vessel wall. CR
stalk
was calculated as the ratio of post-contrast CAWE over pituitary stalk enhancement. RVE was assessed in the mid-BA for aneurysms in the anterior circulation, and the MCA (M1 segment) for posterior circulation aneurysms. Correlation statistics were performed to find any significant association between CAWE, CR
stalk
, PVE and RVE.

Results:
Nineteen patients with 20 aneurysms were included. Mean age was 68.9 ± 9.9 years old, and 16 (84.2%) were women. Pearson and Spearman coefficients’ analyses demonstrated a strong positive correlation between post-contrast CAWE and PVE (0.72 and 0.73, both
P
<.001), whereas the correlation between post-contrast CAWE and RVE was low (both 0.47,
P
=.04). A stronger correlation was found between CR
stalk
and post-contrast PVE (Pearson = 0.82, Spearman = 0.71, both
P
<.001), while the correlation between CR
stalk
and post-contrast RVE was negligible (Pearson = 0.33,
P
=.15; Spearman = 0.38,
P
=.09).

Conclusion:
This HR-VWI study shows that the parent vessel of unruptured intracranial aneurysms enhances more with contrast than vessels located in other vascular territories. This finding suggests that a local inflammatory/vasculopathic process in the wall of the parent artery may lead to aneurysm formation.
Abstract 158: Progression of Microvascular Brain Disease and Stroke Incidence in the Atherosclerosis Risk in Communities Study
Authors: Koton Silvia , Schneider Andrea L , Windham B. Gwen , Mosley Thomas H , Gottesman Rebecca F , Coresh Josef
Published: June 2021

Background and Purpose:
Data on the significance of combined white matter hyperintensities (WMH)/lacunar brain infarcts measures progression for the incidence of clinical stroke are scarce. We aimed to study associations between the progression in measures of microvascular brain disease over time and risk of stroke in the Atherosclerosis Risk in Communities (ARIC) Study.

Methods:
We analyzed data on 907 ARIC participants who underwent a brain MRI in 1993-95, a second brain MRI in 2004-6, and were subsequently followed for incident stroke through December 31
st
, 2017 (median [IQR] follow-up of 12.6 [8.9-13.4] years from the second brain MRI in 2004-6). At each MRI, WMH was categorized according to the Cardiovascular Health Study 0-9 rating scale and scans were centrally reviewed for lacunar infarcts. A combined measure of microvascular brain disease was defined, and progression from the first to the second brain MRI, manifesting as new WMHs and lacunes at the second brain MRI, was categorized as: no progression; increase of ≥1 unit in WMH grade
or
incident lacune; increase of ≥1 unit in WMH grade
and
incident lacune. All fatal and non-fatal strokes occurring in the participants during the study period, and adjudicated as definite/probable ischemic or hemorrhagic incident stroke, were included in this analysis. Associations between progression of microvascular brain disease and incidence of stroke were studied with Cox proportional hazard models, adjusting for age, gender, race, education level, BMI, smoking, hypertension, diabetes and coronary heart disease.

Results:
At the second brain MRI (mean age 72y), no progression in the combined measure of microvascular disease was found in 38% of participants, while 57% showed ≥1 unit increase in WMH grade
or
new lacune, and 5% showed increased WMH grade
and
new lacune. Sixty-four incident strokes occurred during follow-up. Compared to no change in the combined measure, progression of microvascular brain disease expressed as ≥1 unit increase in WMH grade
and
incident lacune was significantly associated with higher risk of stroke (adjusted HR 3.01, 95% CI 1.30-6.95).

Conclusion:
Progression of combined measures of microvascular brain disease over a decade is associated with a significant increased risk of stroke.
Abstract 162: 12-Month Epilepsy Outcomes in Patients With Acute Ischemic Stroke 12-Month Epilepsy Outcomes in Patients With Acute Ischemic Stroke
Authors: Chiquete Erwin , Ramirez-Garcia Guillermo , Sandoval-Rodriguez Valeria , Flores-Silva Fernando , Ruiz-Sandoval Jose L , Cantu-Brito Carlos
Published: June 2021

Background and purpose:
Acute ischemic stroke (AIS) is the leading cause of adult-onset epilepsy. In the context of current guidelines, AIS patients presenting with seizures are considered at high risk for seizure recurrence and as a consequence, this patients are deemed as nowadays affected by epilepsy. We aimed to describe the factors associated with acute seizures, epilepsy and seizure recurrence after AIS, as well as their impact on the functional outcome at 12-month follow-up.

Methods:
This is a cohort study on 1,246 non-epileptic patients with AIS included in a multicenter Mexican registry; who received 12-month follow-up after a first-ever or recurrent AIS. Multivariate analyses were performed to evaluate factors associated with acute seizures and the functional outcome at 12 months of follow-up.

Results:
The frequency of acute seizures (within 7 days after stroke onset) after AIS was 8.1% [95% confidence interval (CI): 6.7% to 9.8%]. In all, 12-month seizure recurrence rate was 4.8% (95% CI: 3.7% to 6.1%). In a binary logistic regression model, risk factors significantly associated with seizures were >10 scoring of the National Institutes of Health Stroke Scale (NIHSSS, US) [odds ratio (OR): 2.21, 95% CI: 1.40-3.47], recurrent ischemic stroke (OR: 2.17, 95% CI: 1.34-3.53) and age <65 years (OR: 1.69, 95% CI: 1.09-2.62). After a Cox-proportional hazards model and Kaplan-Meier actuarial analyses, the presence of acute seizures was significantly associated with the risk of functional disability or death (a modified Rankin scale >3) at 12 months of follow-up [hazard ratio (HR): 1.37, 95% CI: 1.04-1.83], as well as NIHSS >10 (HR: 4.47, 95% CI: 3.53-5.65), age ≥65 years (HR: 1.74, 95% CI: 1.38-2.20), heart failure (HR: 1.61, 95% CI: 1.22-2.13) and atrial fibrillation (HR: 1.35, 95% CI: 1.05-1.74).

Conclusions:
The frequency of provoked seizures after acute ischemic stroke in this cohort was 8%. Age <65 years and severity of the brain infarction are the main factors associated with seizures, which in turn represent an important risk factor for functional disabilities or death one year after the acute event.
Abstract 165: Automated Stroke-Related Information Extraction From Diagnostic Imaging Reports Using Natural Language Processing
Authors: Liu Zhongyu Anna , Mamdani Muhammad , Aviv Richard , Pou-Prom Chloe , Yu Amy
Published: June 2021

Introduction:
Diagnostic imaging reports contain important data for stroke surveillance and clinical research but converting a large amount of free-text data into structured data with manual chart abstraction is resource-intensive. We determined the accuracy of CHARTextract, a natural language processing (NLP) tool, to extract relevant stroke-related attributes from full reports of computed tomograms (CT), CT angiograms (CTA), and CT perfusion (CTP) performed at a tertiary stroke centre.

Methods:
We manually extracted data from full reports of 1,320 consecutive CT/CTA/CTP performed between October 2017 and January 2019 in patients presenting with acute stroke. Trained chart abstractors collected data on the presence of anterior proximal occlusion, basilar occlusion, distal intracranial occlusion, established ischemia, haemorrhage, the laterality of these lesions, and ASPECT scores, all of which were used as a reference standard. Reports were then randomly split into a training set (n= 921) and validation set (n= 399). We used CHARTextract to extract the same attributes by creating rule-based information extraction pipelines. The rules were human-defined and created through an iterative process in the training sample and then validated in the validation set.

Results:
The prevalence of anterior proximal occlusion was 12.3% in the dataset (n=86 left, n=72 right, and n=4 bilateral). In the training sample, CHARTextract identified this attribute with an overall accuracy of 97.3% (PPV 84.1% and NPV 99.4%, sensitivity 95.5% and specificity 97.5%). In the validation set, the overall accuracy was 95.2% (PPV 76.3% and NPV 98.5%, sensitivity 90.0% and specificity 96.0%).

Conclusions:
We showed that CHARTextract can identify the presence of anterior proximal vessel occlusion with high accuracy, suggesting that NLP can be used to automate the process of data collection for stroke research. We will present the accuracy of CHARTextract for the remaining neurological attributes at ISC 2020.
Abstract 170: Impact of Eloquent Motor Cortex-Tissue Reperfusion Beyond the Traditional TICI Scoring After Thrombectomy
Authors: Raychev Radoslav I , Saver Jeffrey , Brown Scott , Duckwiler Gary , Jahan Reza , Tateshima Satoshi , Szeder Viktor , Colby Geoffrey , Nour May , Rao Neal , Starkman Sidney , Hinman Jason , Restrepo Lucas , Sharma Latisha , Kim Doojin , Bahr Hosseini Mersedeh , Liebeskind David
Published: June 2021

Background:
Targeted eloquence-based tissue reperfusion within the primary motor cortex may have differential effect on disability as compared to the traditional volume-based (TICI) reperfusion after endovascular thrombectomy (EVT) in setting of acute ischemic stroke (AIS).

Methods:
We explored the impact of eloquent reperfusion (ER) within primary motor cortex (PMC) on clinical outcome (mRS) in AIS patients undergoing EVT. ER was defined as presence of flow on final digital subtraction angiography (DSA) within four main cortical branches, supplying the PMC (MCA - precentral, central, anterior parietal; ACA- pericallosal) and graded as absent (0), partial (1), and complete (2). Prospectively collected data from two centers were analyzed. Multivariable analysis was conducted to assess the impact of ER on 90-day disability (mRS) among patients with anterior circulation occlusion who achieved partial reperfusion (TICI 2 a and b).

Results:
Among the 125 patients who met study criteria, median age was 73, median NIHSS was 16, median ASPECTS was 7, 48% (60/125) were female, and 36.8% achieved functional independence (mRS 0-2) at 90 days. ER distribution was: Absent (0) in 19/125 (15.2%); Partial (1) in 52/125 (41.6%), and Complete (2) in 54/125 (43.2%). TICI 2b was achieved in 102/125 (81.6%) and ER was substantially higher in those patients (p<0.001). In multivariate analysis, in addition to age and sICH, ER had a profound independent impact on 90-day disability (OR 6.10, p=0.001 for ER 1 vs 0; and OR 9.87, p<0.001 for ER 2 vs 0). In contrast, extent of total partial reperfusion (TICI 2b vs 2a) was not related to 90-day disability.

Conclusions:
Our findings support that eloquent PMC-tissue reperfusion is a major determinant of functional outcome, more impactful than volume-based degree of partial reperfusion. More aggressive, PMC-targeted revascularization among patients with non-eloquent partial reperfusion may further improve post-stroke disability after EVT.
Abstract 171: Endovascular Thrombectomy May Be Cost-Effective for Patients With Large Core Ischemic Strokes: A Cost-Utility Analysis From the SELECT Study
Authors: Pizzo Elena , Lobotesis Kyriakos , Albers Gregory W , Martin-Schild Sheryl , Hassan Ameer , Abraham Michael , Vora Nirav , Chen Peng R , Grotta James C , Sitton Clark , Blackburn Spiros , Dannenbaum Mark , Cai Chunyan , Parsha Kaushik , Reddy Sujan , Kamal Haris , Arora Ashish , Pujara Deep , Imam Bita , Shaker Faris , Barreto Andrew D , Hicks William J , Riascos Roy F , Haussen Diogo , Gupta Rishi , Lansberg Maarten , McCullough Louis D , Savitz Sean I , Sarraj Amrou
Published: June 2021

Background:
Whether Endovascular Thrombectomy (EVT) is cost-effective in large ischemic core infarcts is unknown.

Methods:
In the prospective multicenter cohort study of imaging selection study (SELECT), large core was defined as CT ASPECTS < 6 or CTP ischemic core volume (rCBF<30%) ≥ 50 cc. A Markov model estimated costs, quality-adjusted life years (QALYs) and the Incremental Cost-effectiveness Ratio (ICER) of EVT compared to Medical Management (MM) over 20 years life expectancy. The lower and upper willingness to pay (WTP) per QALY were set at $50000 and $100000 and the Net Monetary Benefit (NMB) for EVT were calculated. A probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEAC) assessed EVT cost-effective probability at WTP range values.

Results:
Of 361 enrolled, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT patients achieved mRS 0-2 vs 6 (14%) MM (aOR: 3.27, 95% CI: 1.11-9.62;
P
= .03) with a shift towards better mRS (adj cOR: 2.12, 95% CI: 1.05-4.31,
P
= .04). Over 20 years EVT was associated with $26589 (C.I. $8672- $43978) incremental costs and a gain of 1.18 QALYs (C.I. 0.091- 2.2) per patient.

EVT could avert 75 deaths over a theoretical cohort of 1000 patients (MM 861 vs EVT 786) thus the ICER of EVT compared to MM was $22400 per QALY (CI. $10109 - $66140), which is <$50000/QALY, Tab 1.

EVT has a higher NMB compared to MM at the lower and upper WTP thresholds (EVT $86,3 and 271,4 million vs MM $53,6-$179,3 million), Tab 2.

The PSA confirmed the results (fig 1). The CEAC showed 94% and 97% cost-effectiveness probability of EVT at the lower and upper values respectively of the maximum WTP, fig 2.

EVT ICER in SELECT large core ($22400/QALY) was higher but still comparable to those in HERMES ($16882/QALY), DAWN ($7335/QALY) and DEFUSE3 ($14673/QALY), Tab 3.

Conclusion:
EVT may result in better outcomes and more lives saved in large core patients with higher QALYs, NMB and an acceptable ICER. The results were comparable to other EVT RCTs.
Abstract 174: Regulation of Post-Stroke Gene Expression and Pathophysiology by an Enhancer RNA
Authors: Bhattarai Sunil , Akella Aparna , Ghani Asad , Gandhi Atish , Dharap Ashutosh A
Published: June 2021

Enhancer elements orchestrate genomic regulatory interactions to facilitate gene expression and phenotypic changes in development and disease. Recent studies have shown that mammalian enhancers are transcribed into noncoding enhancer RNAs (eRNAs) in a stimulus-dependent manner and some of these eRNAs have central roles in enhancer-mediated gene induction. Due to the very recent discovery of eRNAs, their expression and functions in cerebral ischemia are virtually unknown. Recently, we applied a combination of genome-wide H3K27ac ChIP-seq and genome-wide RNA-seq in ipsilateral cortices from adult male C57BL6/N mice following a 1 h middle cerebral artery occlusion (or sham surgery) and 6 h of reperfusion (n=6/group) to identify enhancer elements and stroke-induced eRNAs. We identified 77 eRNAs that were significantly upregulated (absolute fold-change ≥2.0; q<0.05) in stroke as compared to sham, of which 55 were exclusively expressed in stroke. All 77 eRNAs were novel, unspliced transcripts. Using luciferase reporter assays, we confirmed the enhancer capabilities of multiple eRNA-encoding genomic loci, and using cell fractionation experiments we determined that the eRNAs are preferentially localized to the chromatin, consistent with their eRNA status. Knockdown of one such eRNA in the mouse brain using antisense oligos, followed by a 1 h MCAO and 6 h of reperfusion, resulted in 49 downregulated genes and 106 upregulated genes (absolute fold-change ≥2.0; q<0.05) versus negative controls. The downregulated subset was enriched in several important genes with roles in mitochondrial activity, receptor signaling, ion channels and calcium homeostasis, and the upregulated subset was enriched in genes involved in inflammation and apoptosis. These changes were associated with worsened neurological scores and an 11.9% increase in infarct volume in the eRNA knockdown group versus negative control (p=0.004). This suggests an innate neuroprotective role for the eRNA during the stroke injury. Together, our study presents the first genome-wide identification of stroke-induced eRNAs in the adult cerebral cortex and illuminates the functional importance of one such eRNA in modulating post-stroke cortical gene expression and pathophysiology.
Abstract 180: Women Have Higher Neurological Severity and Worse Functional Outcome Than Men With Similar Infarct Volume and Leukoaraiosis Burden
Authors: Kim Dong-Eog , Ryu Wi-Sun , Schellingerhout Dawid , Bae Hee-Joon ,   Clinical Rsch Cntr for Stroke in Korea - fifth division (CRCS-5)
Published: June 2021

Background:
Women, compared with men, tend to have worse functional outcome after stroke. The gender effect is not fully explained by age, pre-stroke dependency, and stroke severity. We hypothesized that it might be due to different prognostic impacts of stroke-related brain lesions in women vs. men.

Objective:
To investigate if the effects of acute infarct volume and white matter hyperintensity (WMH) volume on initial stroke severity and 3-month functional outcome are modified by gender.

Methods:
This prospective study included 6748 patients with acute ischemic stroke (<1-week) recruited (May 2011 to February 2013) consecutively from 11 academic stroke centers. The volumes (% of brain parenchyma) of acute infarct and WMH were measured in all patients by using diffusion-weighted magnetic resonance images (MRIs) and fluid-attenuated inversion recovery MRIs. Multivariable analyses were performed to test gender-related interactions in the relationship of MR lesion (infarct or WMH) volume (quartiles) with admission NIH stroke scale (NIHSS) score or 3-month modified Rankin scale (mRS) score, after adjusting for relevant covariates.

Results:
Women, compared with men, were older (mean 72 vs. 65, p<0.01), and had more risk factors, a higher admission NIHSS score (median 4 vs. 3; p<0.01), and a higher WMH volume (median 0.98% vs. 0.74%, p<0.01). Acute infarct volume was not different between the two groups (median 0.15% vs. 0.16%, p=0.27), however its impact on the NIHSS score was greater in women than in men (adjusted analysis, p<0.01). At 3 months, women had worse functional outcome than men (mRS>2: adjusted OR [95%], 1.36 [1.09-1.69]). The association of WMH volume with 3-month mRS score was significantly modified by gender (p-for-interaction=0.049), with the WMH effect being greater in women (adjusted ORs of the highest vs. lowest quartile for the worse outcome: 2.47 in women vs. 1.51 in men).

Conclusion:
Women, compared with men, are probably more susceptible to the adverse effects of infarct volume and WMH volume on stroke severity and functional outcome.
Abstract 185: Trends in Care Delivery and Outcomes for Acute Stroke and Transient Ischemic Attacks Among Rural and Urban Medicare Beneficiaries, 2008-2017
Authors: Zachrison Kori S , Wilcock Andrew D , Schwamm Lee H , Uscher-Pines Lori , Zubizarreta Jose R , Mehrotra Ateev
Published: June 2021

Introduction:
Over the last decade substantial investments have been made in implementing stroke systems of care to improve access and quality of care. We sought to determine if these interventions have narrowed the rural-urban disparities in care over time for patients with acute stroke or transient ischemic attack (TIA).

Methods:
Descriptive observational study using data from all traditional Medicare beneficiaries in the United States from 2008-17 who presented to a hospital emergency department and were admitted either under observation stay or inpatient admission. Patients were classified as rural or urban based on home zip code. The main outcomes were rates of presentation to a certified stroke center, neurology consultation during admission, IV altepase, 90-day mortality, days living independently in the first 90 days post stroke, and 90-day spending.

Results:
We identified 3.31 million hospital stays for TIA and stroke in the study period. Rural and urban patients had similar age, race, gender, Medicaid status and presence of chronic conditions. In 2008, 24.4% and 60.4% of rural and urban patients respectively were cared for at a certified stroke center (disparity -36.1%). By 2017 this disparity had narrowed by 8.6% points (95% CI 6.6%,10.7%) (Fig). Between 2008 and 2017, the disparity in neurologist evaluation during admission narrowed by 7.4% (5.2%, 9.6%). However, there was no substantive change in disparity in alteplase use -0.1% (95% CI -0.5%,0.3%), mortality at 90 days 0.4% (95% CI 0.1%, 0.7%), or days living independently within 90 days -0.7 days (95% CI -1.1, 0.2). Spending in the first 90 days differentially increased among rural patients by $867 (95% CI 85, 1649).

Conclusions:
In the last decade, rural residents are more likely to receive care at a certified stroke center and receive neurologist consultation. However, disparities in outcomes are persistent, highlighting more work is needed to equitably extend stroke expertise to all Americans.
Abstract 19: Default Mode Network Alterations in Cerebral Amyloid Angiopathy: A Resting State FMRI Study
Authors: Horn Mitchell J , Gokcal Elif , Frau-Pascual Aina , Schwab Kristin M , Viswanathan Anand , Polimeni Jonathan , Greenberg Steven M , Gurol Edip
Published: June 2021

Introduction:
Cerebral amyloid angiopathy (CAA) is an established cause of intracerebral hemorrhage and vascular dysfunction leading to ischemia. Functional connectivity analysis using MRI is becoming an important tool to analyze the brain activity during resting state, the default mode network (DMN) representing the prototypical set of connections. As CAA pathology has a posterior predominance, we sought to characterize the functional connectivity of the posterior DMN at resting state in patients with CAA.

Methods:
Patients with probable CAA diagnosed using Boston Criteria and healthy controls (HC) were prospectively enrolled and received high resolution 3T MRI scans including dedicated resting-state fMRI sequences. Functional seed-to-seed analyses were done using the default processing pipeline in the CONN Toolbox. Correlation maps between the established DMN and specific regions of the posterior DMN, the precuneus and posterior cingulate, were averaged within groups and compared in an ANCOVA model.

Results:
Study participants consisted of 60 patients with probable CAA and 20 healthy controls [aged 69 ± 7.5 vs 72.3 ± 8 years,
P
= 0.108]. Seed-to-seed analysis revealed a significantly lower strength of DMN connectivity in CAA when compared to controls in the precuneus [
P
= 0.009] and posterior cingulate [
P
= 0.003] adjusted for age and sex (Fig 1).

Conclusion:
Patients with CAA exhibited significant loss of connectivity in the posterior regions of the DMN when compared to controls. The precuneus and posterior cingulate are core regions of the DMN with reportedly high metabolic rates at rest. Disruption of these posterior DMN regions might occur due to vascular amyloid pathology that shows a predominantly posterior distribution.
Abstract 22: Incidence Rate of Atrial Fibrillation in Cryptogenic Stroke: Results From the Reveal LINQ Real-World Registry
Authors: Kasner Scott E , Verma Atul , Mittal Suneet , Natale Andrea , Beinart Sean C , Amin Alpesh , Pouliot Erika , Franco Noreli C , Diener Hans-Christoph
Published: June 2021

Objectives:
To determine the incidence rate of AF in real-world patients with prior cryptogenic stroke (CS) or transient ischemic attack (TIA) and to assess the impact of using an insertable cardiac monitor (ICM) on treatments.

Methods:
The Reveal LINQ registry is an ongoing, observational, multi-center study evaluating the role of the ICM in the patient care pathway. Patients with prior CS or TIA were included. Patients without device data or without any contact after ICM insertion, with a history of AF, prior known atrial ablation, or hemorrhagic stroke were excluded. Device data were adjudicated by at least 2 independent reviewers. Patients were considered to have AF if they had a ≥2 min episode, and to not have AF if no AF was found after 1 year of monitoring. Patients without AF and without 1 year of follow-up were excluded from the general analysis due to limited follow-up time but were included in the AF incidence rates calculation for completeness.

Results:
In total, 192 patients (61±14 years, 61% male, mean CHA2DS2-VASc score 3.8±1.4) from 29 centers in 8 countries were included. Reasons for monitoring were CS (96%) and TIA (4%). During an average follow-up of 19±6 months, AF was detected in 36 (19%) patients and the incidence of first episode of AF ≥2 min, ≥1 h, ≥6 h, and ≥24 h was 16.7%, 7.9%, 3.7% and 1.7% at 24 months, respectively (figure). Patients with AF were older (68±14 years vs. 60±14, p<0.001). Anticoagulant treatment was initiated in 29 (15%) patients during follow-up , while 14 of 45 initially on anticoagulants discontinued the treatment (13 were free of AF after 1-year follow-up and 1 had a single episode). Other AF-related clinical actions included ablations in 5 patients (2.6%), 1 electrical cardioversion (0.5%) and 3 IPG implants (1.6%).

Conclusion:
ICM monitoring in cryptogenic stroke/TIA patients is currently being used by clinicians for treatment decisions, but the impact on clinical events and quality of life requires ongoing investigation.
Abstract 24: Transesophageal Echocardiography and Risk of Acute Respiratory Failure in Patients With Ischemic Stroke and Transient Ischemic Attack
Authors: Bruce Samuel S , Navi Babak B , Kamel Hooman
Published: June 2021

Introduction:
Transesophageal echocardiography (TEE) is often used as an adjunct to transthoracic echocardiography (TTE) to identify sources of cardiac embolism after ischemic stroke and transient ischemic attack (TIA). Unlike TTE, TEE is invasive and may lead to aspiration. Few data exist on the risk of respiratory complications after TEE in patients with stroke and TIA.

Methods:
We performed a retrospective cohort study using inpatient and outpatient claims data between 2008 through 2016 from a 5% sample of Medicare beneficiaries. We included patients ≥65 years old and hospitalized with acute ischemic stroke or TIA, defined by validated ICD-9 and ICD-10 diagnosis codes. CPT codes and ICD procedure codes were used to ascertain whether TEE, endotracheal intubation, mechanical ventilation, intravenous thrombolysis, or mechanical thrombectomy were performed during the stroke/TIA hospitalization. The exposure was TEE, modeled as a time-varying covariate, and the outcome was acute respiratory failure, defined as endotracheal intubation and/or mechanical ventilation. Patients were censored at hospital discharge or 21 days from admission. Cox proportional hazards regression was used to adjust for age, race, Charlson comorbidities, diagnosis of stroke versus TIA, thrombolysis, and thrombectomy.

Results:
Of 103,072 patients included during the study period, 72,981 (70.8%) had a diagnosis of ischemic stroke and 30,091 (29.2%) had a diagnosis of TIA. A total of 5,096 (4.9%) underwent TEE. The cumulative rate of respiratory failure at 21 days was higher after TEE (13.1%; 95% CI, 8.8-19.2%) than in patients without TEE (9.7%; 95% CI, 8.7-10.9%). After adjustment for potential confounders, TEE was associated with an increased risk of intubation (HR, 1.6; 95% CI, 1.3-2.0). This association was present when we assessed TIA patients only (HR, 2.7; 95% CI, 1.1-6.8).

Conclusions:
In a large cohort of Medicare beneficiaries, we found that TEE was associated with an increased risk of respiratory failure in patients with ischemic stroke or TIA.
Abstract 27: Biomarkers of Coagulation and Hemostatic Activation in the Post-Acute Period Effectively Rule Out Hypercoagulable States in Patients With Embolic Stroke of Undetermined Source
Authors: Liu Michael , Rangaraju Srikant , Ellis Deandrea , Duncan Alexander , Belagaje Samir , Belair Trina , Henriquez Laura , Nahab Fadi
Published: June 2021

Introduction:
We previously reported that markers of coagulation and hemostatic activation (MOCHA) have been associated with malignancy, venous thromboembolism (VTE) and hypercoagulable states in embolic stroke of undetermined source (ESUS) patients. The objective of our study was to identify independent predictors of these endpoints.

Methods:
Consecutive ESUS patients seen at the Emory Clinic from January 1, 2017 to June 30, 2019 underwent a MOCHA profile (d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) and were followed prospectively for new diagnoses of malignancy, VTE, other defined hypercoagulable states and the composite outcome. Abnormal MOCHA was defined as ≥ 2 elevated markers. Multivariable analyses were performed to identify predictors of the composite outcome.

Results:
Of 188 patients (mean age 63 ±16 years, 59% female, 50% Caucasian) included in the study period, 25 (13%) had the composite outcome. The median time between ESUS to MOCHA testing was 45 days (IQR 23-88). Abnormal MOCHA profile was the only independent predictor of the composite outcome (OR 2.34, 1.64-3.32, p<0.001) (AUC 0.824); age, sex, race, any history of tobacco use, hypertension, diabetes, history of stroke, cortical stroke, migraine, and left atrial size were not predictive. Abnormal MOCHA had a 96% sensitivity, 32% positive predictive value and 99% negative predictive value for the composite outcome.

Conclusions:
This study confirms that a normal MOCHA profile in the post-acute time period can rule out ESUS patients with malignancy, VTE or other underlying hypercoagulable states.