bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP184: Identifying Optimal Cut Points Of National Institutes Of Health Stroke Scale To Predict Mortality: A Population-based Assessment
Authors: Stanton Robert J , Robinson David , Ding Lili , Khoury Jane C , Reeves Mathew J , De Los Rios La Rosa Felipe , Haverbusch Mary , Alwell Kathleen S , Ferioli Simona , Demel Stacie L , Jasne Adam , Slavin Sabreena , Walsh Kyle B , Star Michael , Adeoye Opeolu M , Khatri Pooja , Coleman Elisheva , Mackey Jason , Mistry Eva , Martini Sharyl R , Flaherty Matthew L , Woo Daniel , Kissela Brett , Kleindorfer Dawn O
Published: February 2023

Background:
Ischemic stroke is the 5
th
leading cause of death in the US. As a measure of stroke severity, initial NIHSS has been used to predict clinical outcome. We sought to identify the optimal cut-points of NIHSS at initial presentation that are associated with higher 30-day mortality.

Methods:
In 2005, 2010, and 2015 all hospitalized, first acute ischemic stroke events occurring within the Greater Cincinnati area were ascertained. Potential ischemic stroke cases underwent chart abstraction and physician adjudication, including retrospective NIHSS score (range 0 - 42) based on clinical findings at initial presentation. Descriptive statistics for NIHSS were estimated by study year, demographics, and medical history. Data regarding mortality was obtained from the National Death Index. The Contal and O’Quigley method based on a modified log-rank test statistic was used to determine cut-points of the NIHSS score associated with 30-day mortality, and hazard ratios were obtained from Cox models with adjustment for sex, race, and age.

Results:
In 2005, 2010, and 2015 there were 1704, 1818 and 1852 ischemic stroke events with 30-day mortality rates of 10.5%, 9.6% and 9.0%, respectively. Optimal cut-points of NIHSS <9, 9-16 and >16 were identified. Across all 3 periods, 3431 (84.5%) cases had NIHSS 0-8, 352 (8.7%) had NIHSS 9-16 and 274 (6.8%) >16. Kaplan Meier Survival Curves for the 3 NIHSS groups are shown in the Figure. Strokes with NIHSS >16 at initial presentation were associated with a 15-fold (HR with 95% CI: 13, 19) increase in the risk of death at 30-days compared to those with NIHSS <9.

Discussion:
NIH Stroke Scale scores are a reliable predictor of mortality, with higher NIHSS scores having higher risk of death. The cut points reported identify subgroups of stroke patients with dramatically different prognoses. Future studies should assess if this excess mortality risk among severe strokes persists after the more widespread implementation of thrombectomy beyond 2015.
Abstract WP201: Outcomes Of Ischemic And Hemorrhagic Stroke Patients With Cancer: Japan Stroke Data Bank
Authors: Yoshimoto Takeshi , Toyoda Kazunori , Wada Shinichi , Yoshimura Sohei , Sasahara Yusuke , Iwanaga Yoshitaka , Miyamoto Yoshihiro , Kobayashi Shotai , Minematsu Kazuo , Koga Masatoshi
Published: February 2023

Purpose:
We aim to clarify the association between history of cancer with clinical outcomes after ischemic stroke (IS) or hemorrhagic stroke (HS).

Methods:
Study participants were adult patients within seven days after onset of IS or HS from the register of the Japan Stroke Data Bank, a hospital-based multicenter stroke registration database, between 2000 and 2021, whose modified Rankin Scale score at discharge was available. Participants were divided into three groups [active cancer (AC) group, inactive cancer (iAC) group, and without cancer group]. Outcomes including good functional outcome, representing modified Rankin Scale score 0-2 at discharge, and in-hospital death was compared between the groups using multivariate analysis by forward-backward stepwise selection method for stroke subtype. AC was defined as cancer diagnosed within six months, requiring chemotherapy or surgical treatment, metastatic, or inoperable.

Results:
Of 171292 stroke patients, including 128145 with IS and 43147 with HS, 1074 patients had AC (women 42.5%; median age, 77 years; median (interquartile range) baseline National Institutes of Health Stroke Scale 5 [2–15]; IS 84.3%), 6337 patients had iAC (37.9%; 73 years; 4 [2–13]; 79.5%), and 163881 patients did not have cancer (42.4%; 73years; 4 [2–12]; 74.6%). Good functional outcome after IS was less common in cancer patients [AC; 39.4%, adjusted odds ratio (OR) 0.78, 95% confidence interval (CI) 0.71-0.86: iAC; 49.1%, adjusted OR 0.92, 95% CI 0.85-0.99] than those without cancer (56.3%), and mortality in cancer patients was higher (AC; 10.6%, adjusted OR 1.77, 95% CI 1.56-2.01: iAC; 5.6%, adjusted OR 1.26, 95% CI 1.09-1.47) than those without cancer (4.4%). Good functional outcome after HS was less common in cancer patients [AC; 22.0%, adjusted OR 0.81, 95% CI 0.61-1.07: iAC; 24.6%, adjusted OR 0.78, 95% CI 0.64-0.94] than those without cancer (35.3%), and mortality after HS was higher in AC patients (29.8%) than those without cancer (15.9%, adjusted OR 1.61, 95% CI 1.26-2.07)

Conclusions:
IS patients with AC and those with iAC significantly had less achievement of good functional outcomes and more in-hospital death, and HS patients with AC led to more in-hospital death than patients without cancer.
Abstract WP204: Real World Data On Spontaneous Cervical Artery Dissection From A Comprehensive Stroke Center
Authors: Mandel Daniel , Shu Liqi , Pan Kelly , Baumgartner Karl V , Dantu Vishnu , Goldstein Eric , Burton Tina , Furie Karen L , Yaghi Shadi
Published: February 2023

Introduction:
Cervical artery dissection (CAD) is a common cause of stroke in the young and carries a high risk of early recurrence. We aim to compare the characteristics of patients from a real-world cohort to those from prior randomized controlled trials.

Methods:
We pooled data from consecutive patients with a diagnosis of spontaneous CAD treated at a comprehensive stroke center who were followed for at least 90 days. We excluded patients with traumatic dissection and those with primary intracranial hemorrhage in the setting of trauma or dissection. We compared the baseline characteristics and stroke recurrence rates in our cohort to the TREAT-CAD (2021) and CADISS (2019) trials. We report recurrence rates in patients treated with single antiplatelet (SAPT), dual antiplatelet (DAPT), and anticoagulation (AC).

Results:
80 patients with CAD met our inclusion criteria. Our study sample characteristics differ from TREAT-CAD and CADISS, with our cohort more likely to have hypertension and diabetes but less likely to have a smoking history. The rate of recurrent stroke at 90 days was numerically higher in our patient cohort (6.3%) compared to TREAT-CAD (3.6%) and CADISS (1.6%). The rates of recurrent stroke were 8.6% (3/35) with SAPT, 4.2% (1/24) with DAPT, and 5% (1/20) with AC strategies.

Conclusions:
Characteristics of a real-world CAD population differ from those enrolled in clinical trials with an overall higher rate of recurrent stroke but comparable rates among patients treated with DAPT and AC. The ongoing STOP-CAD study will compare DAPT to AC with a substantially larger number of patients, with an estimated projection of at least 3000 patients in a multi-center international cohort.
Abstract WP212: Association Of Thrombin Generation With Leukocyte Inflammatory Profile In Patients With Acute Ischemic Stroke
Authors: Falcione Sarina , Munsterman Danielle , Joy Twinkle , KAMTCHUM TATUENE Joseph , Sykes Gina , Jickling Glen
Published: February 2023

Thrombosis is central to the pathogenesis of acute ischemic stroke, with higher thrombin generation being associated with increased stroke risk. The immune system may contribute to thrombin generation in stroke and thus may offer novel strategies for stroke prevention. This study addresses the research question regarding the relationship of thrombin generation to leukocyte gene expression in patients with acute ischemic stroke. We isolated RNA from whole blood and examined the relationship to thrombin generation capacity in patients with acute ischemic stroke. Due to its effects on thrombin generation, patients on anticoagulants were excluded from the study. The relationship of gene expression with peak thrombin was evaluated by analysis of covariance across peak thrombin quartiles adjusted for sex and age. In 97 patients with acute ischemic stroke, peak thrombin was variable, ranging from 252.0 to 752.4 nM. Increased thrombin generation was associated with differences in thromboinflammatory leukocyte gene expression, including a decrease in ADAM metallopeptidase with thrombospondin type 1 motif 13 and an increase in nuclear factor B (NF-kB)-activating protein, protein disulfde isomerase family A member 5, and tissue factor pathway inhibitor 2. Pathways associated with peak thrombin included interleukin 6 signaling, thrombin signaling, and NF-kB signaling. A linear discriminant analysis model summarizing the immune activation associated with peak thrombin in a first cohort of stroke could distinguish patients with low peak thrombin from high peak thrombin in a second cohort of 112 patients with acute ischemic stroke.The identified genes and pathways support a role of the immune system contributing to thrombus formation in patients with stroke. These may have relevance to antithrombotic strategies for stroke prevention.
Abstract WP213: The Effect Of Nicotine Withdrawal On Stroke Outcome In Female Rats
Authors: Patel Shahil H , Saul Isabel , Dave Kunjan R , Perez-Pinzon Miguel A , Raval Ami P
Published: February 2023

Significance:
Smoking-derived nicotine (N) is known to synergistically magnify the risk and severity of cerebral ischemia in females. Most importantly, smoking is the one preventable risk factor and giving up smoking reduces the risk for cerebral ischemia. However, how long the harmful effects of N on the brain persist after women stop smoking is unknown. In a laboratory study using an animal model of cerebral ischemia, we demonstrated that N alters brain energy metabolism and thus exacerbates ischemic brain damage. Therefore, the current study aims to investigate how long after N withdrawal (NW) N toxicity on brain energy metabolism persists and its impact on stroke outcomes in female rats.

Methods:
Female Sprague-Dawley rats (n=8/group) were randomly exposed to either saline or N (4.5 mg/kg) for 16-21 days after which point, they were withdrawn from N exposure and able to recover for 0, 15, or 30 days. These rats were then randomly assigned to either have their cortical tissue collected for global metabolomic (Metabolon Inc) and Western blot analysis or undergo a sham surgery or transient middle-cerebral artery occlusion (tMCAO; 90 min). Post-stroke cognition was tested with contextual fear conditioning at month following tMCAO, subsequently the brains were collected for infarct quantification.

Results:
Analysis of the metabolomics data revealed an increase in carbohydrate metabolites in the 30-day NW group when compared to the N-exposed group, suggesting persistence of N toxicity in the brain. Furthermore, fear conditioning data revealed a significantly lower freezing time in all NW groups when compared to the saline group implying that spatial memory deficits persist even after 30 days of NW. Lastly, the observed infarct volume was 26%(p<0.05), 25%(p<0.05), and 16%(p<0.05) higher in the 0, 15, and 30 day NW groups respectively, when compared to the saline group.

Conclusion:
Even after 30 days of NW, N-induced global metabolomic changes in the brain persist and may be responsible for increased ischemic brain damage as well as cognitive deficits in female rats.
Abstract WP219: Repurposing The K
Ca
3.1 Inhibitor Senicapoc For Treatment Of Acute Ischemic Stroke
Authors: Weinstein Jonathan R , Lee Ruth D , Chen Yi-je Jay , Adler-Wachter Mitzi , Schweitzer Brendan , McDonough Ashley , Wulff Heike
Published: February 2023

Background:
Acute ischemic stroke (AIS) is a leading cause of death and long-term disability. Both microglia (MG) and infiltrating macrophages (MP) are critical effector cell types in ischemic brain injury and recovery. K
Ca
3.1 is a calcium-activated potassium channel that is upregulated in reactive MG and MP. Studies using either genetic deletion or pharmacological inhibition of K
Ca
3.1 demonstrated that this channel is critical for pro-inflammatory activation of MG/MP as well as exacerbation of stroke pathophysiology. Senicapoc (ICA-17043) is a K
Ca
3.1-specific inhibitor that has been used in human clinical trials for non-neurological indications (sickle cell anemia, asthma) and was proven safe. Here we evaluate the potential for repurposing senicapoc for AIS.

Methods:
Young adult male and female mice underwent 60 min middle cerebral artery occlusion (MCAO)/reperfusion. MCAO was monitored by laser doppler. Senicapoc’s pharmacokinetic (PK) profile was determined using high performance liquid chromatography - mass spectroscopy. Drug levels in plasma and brain were quantified at multiple time points post administration. Effects of senicapoc on post-stroke release of cytokines/chemokines was determined by multiplex ELISA. Inflammatory infiltrates were quantified with flow cytometry. Efficacy studies included: (i) infarct volume (MRI T2), white matter integrity (DTI) and longitudinal neurobehavioral outcomes (NBO).
In-vitro
chromogenic assay was used to assess senicapoc’s effect on proteolytic activity of tissue plasminogen activator (tPA).

Results:
Administration of senicapoc (40 mg/kg, i.p.) twice daily for seven days starting 12 h after MCAO resulted in ~55% reduction in infarct volume with corresponding improvements in NBO. Free senicapoc levels in brain ranged from 20 - 200 nM in stroked mice at 1, 4 & 12 hours following administration. All values exceeded senicapoc’s IC
50
(11 nM) for K
Ca
3.1. Senicapoc, at up to 5 μM, had no effect on tPA’s proteolytic activity.

Conclusions:
We provide proof-of-concept data that senicapoc, administered in an extended temporal window, can markedly reduce infarct volume and improve NBO in a mouse model of AIS. Senicapoc demonstrated favorable PK and CNS penetration. It did not interfere with tPA.
Abstract WP22: Time Is Brain: Improving Door To Thrombolytic Times Through A Multidisciplinary Approach
Authors: Theodore Karen S , Beskid Michelle , Bonnett Jennifer , Kaminiski Erin , Stith Kyle , Vicarel Laine , McCullough Lori , Savetski Mike
Published: February 2023

Background:
Research supports stroke as the 5th leading cause of death in the United States and the leading cause of long term disability. As a primary stroke center, it is necessary to establish and meet stroke standards of care. The American Heart Association Target: Stroke Phase III initiative focuses on timely intravenous thrombolytic administration. A community hospital primary stroke center encountered challenges with meeting established goal times. To improve rapid treatment times and patient outcomes, a multidisciplinary team collaborated to improve workflow.

Purpose:
To decrease door to thrombolytic therapy times in eligible ischemic stroke patients.

Methods:
As a result of retrospective chart audit findings from January through December 2020, a new workflow process was developed, which included: • Education with EMS regarding pre-notification • Relocating a weighted, zeroed patient bed near the ambulance entrance to obtain an accurate weight • Patient going directly to the computed tomography scanner accompanied by the entire stroke team • Earlier activation of the Tele stroke neurologist • Relocating the Tele stroke monitor to the computed tomography scanner area for immediate assessment • Pharmacist at bedside to assist with medication preparation • Real time feedback and data sharing

Results:
In 2021, the new work flow resulted in a 48% time reduction in door to IV thrombolytic administration times. Median door to IV thrombolytic times decreased from 58 minutes to 28 minutes with 75
%
of the population receiving IV thrombolytic therapy in 30 minutes or less.

Conclusions:
A redesigned workflow process, along with a multidisciplinary team approach led to significantly decreased door to thrombolytic therapy times. Key success factors included a consistent team approach, feedback, education, and data sharing for continual improvement.
Abstract WP225: Rapid Complement Activation Induced By Acute Hyperglycemia Worsens Ischemic Stroke Outcome
Authors: Chen Hansen , Chiang Terrance , Kim Anika , Tomlinson Stephen , Bliss Tonya , Cheng Michelle Y , Steinberg Gary
Published: February 2023

Background:
Acute hyperglycemia, which occurs in over 40% of ischemic stroke patients regardless of pre-existing diabetes, increases brain edema, hemorrhagic transformation (HT) and worsens stroke outcome. Understanding the mechanisms of hyperglycemia-exacerbated stroke injury will be vital for developing novel treatments. Here we identify systemic complement activation as a novel contributor to hyperglycemic-exacerbated damage in rodent stroke.

Method:
Male C57/BL6 mice (10-11 weeks) were subjected to middle cerebral artery occlusion (MCAO) for 30 min, followed by reperfusion to mimic ischemic stroke. Acute hyperglycemia was induced by glucose injection 10 min before MCAO. To assess the effect of hyperglycemia on stroke outcomes, mice were sacrificed at 4.5 and 24 hr post-stroke to analyze brain edema, blood-brain barrier (BBB) leakage, and HT; or allowed to survive 14 days to examine mortality rate, neurological deficit, and motor-sensory dysfunction using the horizontal rotating beam test. Complement activation was evaluated at 1, 2, 4.5 hr post-stroke. To inhibit C3 activation, the targeted complement inhibitor CR2-Crry fusion protein, or PBS control, was injected via femoral vein 15 min after reperfusion.

Result:
Hyperglycemia worsens stroke outcomes in our mouse model, with rapid increased BBB leakage (p<0.0001), brain swelling (p<0.001) and HT at (p<0.0001) 4.5 and 24 hr after stroke compared to normoglycemia; and poorer prognosis including higher mortality (100% VS 25%, p=0.0008), body weight loss, and impaired behavioral performance by day 14. Interestingly, acute hyperglycemia rapidly increased plasma complement C3 levels at 1 and 2 hr after stroke (p<0.01 compared to normoglycemic mice), accompanied by activation of C3 in ischemic brain vessels as indicated by elevated levels of vascular C3d. Vascular C3d colocalized with IgM/IgG, suggesting the involvement of classical pathway in C3 activation. Notably, activated C3 levels positively correlated with brain swelling and HT (p<0.01). Inhibition of C3 by CR2-Crry markedly reduced brain swelling (p<0.05) and HT in hyperglycemic stroke.

Conclusion:
Rapid activation of complement C3 by acute hyperglycemia may be an important contributor to BBB leakage, brain swelling and HT.
Abstract WP226: Circadian Rhythm Influences Immune Response In Ischemic Stroke Mice
Authors: Kamat Pradip K , Khan Mohammad B , Baban Babak , Siddiqui Shahneela , Hess David C
Published: February 2023

Background:
Stroke leads to disability and death worldwide. There is evidence that stroke affects the immune system function, and the clock gene controls the immune system. Stroke elevates the inflammatory cascade. Immune response controls the stroke pathology. However, it is unclear if the circadian rhythm influences the immune system in ischemic stroke mice and affects stroke outcomes.

Hypothesis:
We hypothesized that immune response might be affected by a circadian rhythm that aggravates stroke pathology in a mouse suture occlusion model

Methods:
Seven to eight-month-old C57BL/6J (Wild Type, n=8-10 mice/group) mice were randomly assigned to do stroke at the different time points of the day following zeitgeber time at ZT0, ZT6, ZT12, and Z18. Cerebral Ischemia was induced by occlusion of the middle cerebral artery (MCAO) for 60 min. Whole blood was analyzed using flow cytometry, and we observed macrophages (M1, M2), neutrophils (N1, N2), Anti-inflammatory IL10, and pro-inflammatory TNF-α cytokines at 24h and 48h. Forty-eight hours after stroke, TTC staining was done to estimate brain infarction, and the infarct area was measured using NIH-Image J software.

Results:
There was a significant increase (
p
<0.005) in TNF-α (9±2.50) and significant low IL-10 (5.12±1.35) (
p
<0001) at (ZT6, noon) stroke at 48h during a deep sleep period (ZT6, noon) stroke in comparison to fully awake period stroke. We found a significant increase (
p
<001) in M1 (54.12±5.16) macrophage and a significant decrease (
p
<001) in M2 (45.87±5.16) macrophage at ZT6 (noon) compare to other zeitgeber time points. We also found a significantly higher M1:M2 ratio (1.17) at ZT6. Additionally, we found that neutrophil N1 (66.88±4.39) level was significantly (
p
<0001) elevated while neutrophil N2 (33.88±4.43) was significantly reduced at ZT6 (noon) sleep period in comparison to ZT0, ZT12, and Z18 time points. We also found a considerably higher N1:N2 ratio (1.97) at ZT6.

Conclusion:
This study demonstrates that mice brain infarcts are influenced by immune responses that aggravate stroke pathology during their sleep period (noon/ZT6) than during their awake period (midnight/ZT18).
Abstract WP230: Human Peripheral Blood Gene Expression Associated With 90day Ischemic Stroke Outcomes
Authors: Amini Hajar , Knepp Bodie , Rodriguez Fernando , Jickling Glen , Hull Heather , Carmona Paulina , Ander Bradley , Sharp Frank R , Stamova Boryana
Published: February 2023

Objective:
Identifying the molecular underpinnings associated with long-term functional outcome after ischemic stroke (IS) could guide search for treatments for improved outcome. Thus, we identified early peripheral immune gene expression (GE) responses associated with 90-day IS outcome, as measured by the Barthel Index (BI).

Methods:
RNA from 108 samples from three peripheral blood draws (≤3h – before thrombolytic treatment; 5h and 24h - post-treatment) from 36 CLEAR-trial subjects was analyzed on Affymetrix arrays. We performed Analysis of Covariance accounting for treatment (tPA or tPA+eptifibatide), hypercholesterolemia, hypertension, diabetes, age, sex and BI. Genes whose partial correlation with BI was significant (
P
<0.005) were identified.

Results:
There were 206, 865, and 209 genes that significantly correlated with 90-day BI at ≤3h, 5h and 24h post
ictus
, respectively. The gene lists at all three time-points were enriched in B-cell specific genes (hypergeometric probability p<0.05), while the 5h gene list was also enriched in neutrophil-specific genes, and the 24h gene list was also enriched in monocyte-specific genes. B Cell Receptor Signaling pathway was predicted activated in subjects with better 90-day outcome at the ≤3h time-point, while ICOS-ICOSL Signaling in T Helper Cells and Role of NFAT in Regulation of the Immune Response were predicted activated at the 24h time-point.Immune-related pathways were enriched at three time-points including B cell-related, IL-7, and T cell signaling pathways. Apoptosis was suppressed in patients with better 90-day outcome at 3h and 24h post
ictus
. Among the genes associated with the 90-day BI were genes important for stroke and repair after stroke, such as
KCNG1
, Potassium voltage-gated channel subfamily G member 1, which like other potassium channels could modulate stroke outcome.
KCNG1
expression was positively correlated with 90-day BI at ≤3h and 5h.
TERML4
, implicated in inflammatory response and human coronary arterial calcification had expression that positively correlated with BI at all three time-points.

Conclusion:
The findings expand our understanding of the early molecular biology associated with long-term stroke outcome and may serve as potential targets to improve outcome.
Abstract WP241: Phenylalanine, Apob/apoa-1 Ratio, Ketone Bodies, Fatty Acids, And Microrna 9-3p Patterns Are Altered In Acute Ischemic Stroke
Authors: Rout Madhusmita
Published: February 2023

Background:
Stroke is a significant health issue in the United States and identifying biomarkers for prevention and functional recovery of acute ischemic stroke (AIS) remains the highest priority. This study aims to identify metabolite and microRNA (miRNA) signatures that may be associated with AIS pathophysiology by performing longitudinal and case-control studies.

Methods:
We evaluated 260 patients during acute (<72 hours, T1), and chronic (3-5 months, T2) phases of stroke with 160 controls by performing global metabolomics using high-throughput nuclear magnetic resonance spectroscopy. In a subset, we also examined differential expression patterns of blood and serum exosome miRNAs between the T1 and T2 using RNA sequencing.

Results:
Our study identified 19 metabolites to be significantly perturbed during the T1 using the orthogonal partial least square discrimination analysis and multivariate mixed regression. Phenylalanine showed a 15.9-fold increase in T1 and remained high at the T2 stage. The Apolipoprotein B/Apolipoprotein A-1 ratio and ketone bodies were markedly increased while several essential fatty acids and amino acids were decreased in the T1. Our data also identified 3 exosomal miRNAs upregulated in the T1 stage. The miR-9-3p showed a 14.7-fold increase in T1 (Bonferroni p= 9.44x10
-6
) which is strongly supported by the literature to trigger brain injury and cell death via the caspase pathway. Increased expression of miR-4508 correlated positively with phenylalanine both in T1 (r = 0.88, p = 0.001) and T2 (r = 0.71, p = 0.02).

Conclusion:
This study elucidates significant alterations in amino acids, fatty acids, and apolipoprotein patterns between the acute and chronic stages of stroke compared to controls. Our results on exosomal miRNAs and pathway analysis using metabolites identified four major pathways; apoptosis, excitotoxicity, oxidative stress, and stroke-mediated inflammation to play a critical role in the AIS leading to neuronal cell death. Further validation in independent datasets is warranted, and if confirmed some of these may become clinically meaningful biomarkers to predict AIS in humans.
Abstract WP39: Subhairline Electroencephalography For Detection Of Large Vessel Occlusion Stroke
Authors: Groenendijk Eva A , van Stigt Maritta N , Van De Munckhof Anita A , Marquering Henk A , Koelman Johannes H , Potters Wouter V , Coutinho Jonathan M
Published: February 2023

Introduction:
Endovascular thrombectomy (EVT) for large vessel occlusion stroke of the anterior circulation (LVO-a) can only be performed in selected hospitals. A prehospital triage instrument with which paramedics can reliably identify patients with an LVO-a stroke would enable direct routing of these patients to the right hospital and would consequently improve patient outcome. Electroencephalography (EEG) has previously shown to discriminate between patients with and without an LVO-a stroke. In this study, the diagnostic accuracy of subhairline EEG for LVO-a stroke was evaluated.

Methods:
A 3-minute EEG recording was performed in 35 patients who were presented to the emergency room with a suspected stroke or known LVO-a stroke, as soon as possible after presentation, and prior to potential EVT. Recordings were performed using 9 self-adhesive electrodes placed on the forehead and behind the ears. We evaluated the diagnostic accuracies of EEG features quantifying frequency band power (relative delta, theta, alpha and lower beta powers and power ratios), brain symmetry (pairwise derived Brain Symmetry Index [pdBSI]) and connectivity (Magnitude Squared Coherence [MSC] and Weighted Phase Lag Index) for LVO-a stroke using receiver operating characteristic analysis. Optimal cut-off points were determined as the maximum sensitivity at a specificity of ≥ 80% for LVO-a stroke.

Results:
Median age was 75 (IQR 67-81) years and 20/35 (57%) patients were male. 13/35 (37%) patients had an LVO-a stroke, 12/35 (34%) a non-LVO-a ischemic stroke, 4/35 (11%) a transient ischemic attack and 6/35 (17%) a stroke mimic. Median onset-to-EEG-time was 250 (IQR 118-535) minutes. Recordings of all patients were of sufficient quality to calculate frequency band power and brain symmetry measures. The connectivity measures could not be calculated for 3 LVO-a stroke patients. The highest diagnostic accuracy for LVO-a stroke was reached by the MSC in the delta frequency band (AUC 0.80; sensitivity 80%; specificity 82%) and the pdBSI in the theta frequency band (AUC 0.78; sensitivity 77%; specificity 82%).

Conclusions:
Subhairline EEG is a promising instrument for detection of LVO-a stroke, but validation in a larger study population and in the prehospital setting is necessary.
Abstract WP45: VISIION-S: Viz.ai Implementation Of Stroke Augmented Intelligence And Communications Platform To Improve Indicators And Outcomes For A Comprehensive Stroke Center And Network - Sustainability
Authors: Van Orden Kimberlee , Meyer Dawn M , Perrinez Emily , Poynor Briana , Torres Dolores , Alwood Benjamin , Bykowski Julie , Khalessi Alexander A , Meyer Brett C
Published: February 2023

Background:
As Comprehensive Stroke Centers (CSCs) strive to improve neurointerventional (NIR) times, process improvements have been put in place to streamline workflows. Our prior publication (VISIION) demonstrated an improvement in key performance indicators (KPIs) in our CSC. The purpose of this study is to analyze whether the positive results demonstrated were sustainable.

Methods:
Sequential stroke NIR patients being Direct Arriving LVO (DALVO) and telemedicine transfer LVO (BEMI) cases were assessed, including subgroups of DALVO-OnHours, DALVO-OffHours, BEMI-OnHours, and BEMI-OffHours. We analyzed times for the original 6 months pre (6/10/20-1/15/21) and compared them to a 17 months post-implementation (1/16/21- 6/25/22) to evaluate for sustainability. Mann-Whitney U was utilized.

Results:
150 NIR cases were analyzed pre (n=47) v. post (n=103) Viz.ai implementation (DALVO-OnHours 7 v. 20, DALVO-OffHours 10 v. 25, BEMI-OnHours 13 v. 20, BEMI-OffHours 17 v. 38). For Door-to-groin (DTG) assessments, improvement was noted for DALVO-OffHours 39% (157min,96min;p<0.001), DALVO-ALL 25% (127min,95min;p=0.006), BEMI-OffHours 46% (45min,25min;p=0.023), and BEMI-ALL 40% (42min,25min;p=0.005). Activation-to-groin (ATG), door-to-device (DTD), and door-to-recanalization (DTR) showed similar improvements. For DALVO-OffHours, there were significant reductions in door to CT (DTC) 81% (26min,5min;p<0.001), ATG 32% (90min,61min;p=0.036), DTG 39% (157min,96min;p<0.001), DTD 31% (178min,123min;p=0.002), and DTR 32% (197min,135min;p=0.003).

Conclusions:
Consistent with our initial 6 month post-implementation pilot, we noted sustainability over a 17 month period with sustained reduction in KPIs for numerous key NIR subgroups. In the greatest opportunity subgroup (DALVO-OffHours), requiring team mobilization off hours without benefit of telemedicine transfer lead time, we noted a significant reduction in all 5 time metrics. Our sustainability finding is important to show that process improvements continued even after the immediate period, making a Hawthorne effect less likely and adding credibility to the results. Models such as this, could be useful for other centers striving to optimize workflow and improve NIR times.
Abstract WP46: Emergent Large Vessel Occlusion Direct Triage Model Outcomes: A Systematic Review And Meta-Analysis
Authors: Erdman John H , Morey Jacob , Zhang Xiangnan , Kim Brian , Stein Laura K , Redlener Michael , Fifi Johanna T
Published: February 2023

Introduction:
There has been a shift in prehospital systems of care to prioritize transporting acute ischemic stroke (AIS) patients with suspected emergent large vessel occlusion (ELVO) stroke to thrombectomy capable stroke centers (TSCs), as opposed to primary stroke centers (PSCs) which may be closer and offer intravenous thrombolysis faster. Large scale data on clinical outcomes in direct triage are lacking.

Methods:
We conducted a systematic review and meta-analysis using PRISMA guidelines with the Nested Knowledge AutoLit platform to search PubMed for relevant terms from 01/2015 to 05/2022. Our primary endpoint was proportion of patients with a good clinical outcome [modified Rankin Score (mRS) 0-2] at 90 days.

Results:
We identified 390 studies, 16 of which compared direct triage to various models and were included. Amongst these, Mobile Stroke Unit (MSU; n=1), Mothership only (n=1), Drip-and-Ship only (n=3), and Mothership + Drip-and-Ship (n=11) were compared to Direct Triage. Among the eleven that reported 90-day functional status outcomes, there were no discernible trends. Four studies that compared 90-day functional outcomes amongst patients who received EVT and compared Direct Triage to Drip-and-Ship + Mothership models were analyzed. Baseline age, sex, and presenting NIHSS were similar. Patients who underwent Direct Triage were more likely to have a good outcome (mRS 0-2) at 90-days (OR 1.35, 95% CI 1.03-1.76).

Conclusions:
Amongst patients who received EVT, patients who underwent Direct Triage were more likely to have better functional outcomes at 90 days. Direct Triage of AIS patients is a promising strategy to improve clinical outcomes in patients who undergo EVT. More research is needed in patients who do not receive EVT.
Abstract WP5: Act Fast!EMS Sticker Use DecreasesTime To Acute Intervention For Ischemic Stroke Patients
Authors: Davis Nicolle W , Bailey Meghan , Hester Jeannette , Khanna Anna , Wilson Christina A , Bonnell Gabriel , Singh Amita
Published: February 2023

Introduction:
Stroke is a medical emergency requiring timely intervention to optimize patient outcomes. Intravenous (IV) thrombolytics, the only treatment currently FDA-approved for acute stroke, require pertinent medical history for treatment decisions. Key details are often missed in the prehospital setting and during hand-off communication between Emergency Medical Services (EMS) and hospital staff, which can delay the time to treatment. We evaluated if utilization of a ‘stroke alert sticker’ by EMS to capture standardized information in the field would decrease time to thrombolytic administration.

Methods:
A bright orange sticker, to be placed directly on the patient, was disseminated to our local EMS agency for use with all stroke-alert patients. It includes key elements that are important to timely treatment decision, including time last known well, contact information, symptoms, and relevant medications. We evaluated the impact of use of this sticker on acute ischemic stroke treatment metrics, including IV thrombolytic “door to needle” (DTN) time.

Results:
The study included 220 stroke-alert patients brought to our Comprehensive Stroke Center by EMS from May 2021 through February 2022. Mean NIHSS on arrival was 11 (± 9); mean age was 67 (± 16) years; and 52 % were female. 21 patients were treated with an IV thrombolytic. Overall, sticker utilization rate was 40% in the stroke-alert population, but utilization was 60% in patients administered an IV thrombolytic. With sticker utilization, DTN time was reduced by 20 minutes (31 ± 11 min with sticker vs 51 ± 20 min without, p=0.03). In patients who received IV thrombolytics, pre-hospital notification was 100% with sticker use compared to 75% without (p=0.01).

Conclusion:
Utilization of the stroke-alert sticker significantly improved DTN times for acute ischemic stroke patients compared to patients without the sticker. This evidence supports continued use of the stroke alert stickers to improve DTN times and improve patient outcomes. Further research is ongoing in a larger patient cohort.
Abstract WP51: Effect Of Automated Large Vessel Occlusion Detection On Endovascular Therapy Treatment Rate: A Multi-Center Cluster Randomized Clinical Trial
Authors: Dhanjani Saagar , Salazar-Marioni Sergio , Abdelkhaleq Rania , Niktabe Arash , Ballekere Anjan Nagesh , Iyyangar Ananya , Giancardo Luca , Sheth Sunil , Kim Youngran , Martinez-Gutierrez Juan Carlos C
Published: February 2023

Introduction:
Automated Large Vessel Occlusion (LVO) detection and software-based care team integration may improve treatment times. Their effect on likelihood to perform Endovascular Thrombectomy (EVT) in LVO Acute Ischemic Stroke (AIS) patients remains undetermined.

Methods:
We performed a cluster randomized stepped wedge clinical trial across 4 comprehensive stroke centers in the greater Houston area from January 1st 2021 - February 24th 2022. This trial design was chosen due to the impracticality of randomizing at the patient level. An automated LVO detection and workflow manager software (Viz.AI) was implemented at the 4 hospitals in a stepped fashion, with a randomly determined order (Figure 1) . Patients were included if they were diagnosed with LVO AIS based on CT angiogram. Patients who presented during the 2-week transition period at the time of LVO detection software activation were excluded. The primary outcome was proportion of LVO AIS patients treated with EVT adjusted for age, sex and NIHSS and was determined using a mixed-effect logistic regression, with a random effect for cluster (hospital site) and fixed effect for exposure status.

Results:
Among 834 patients that met inclusion criteria, the median age was 68 [58-79] years, NIHSS 13 [5-20], and 50% were female. Median time from last known well to arrival was 298 [102- 754] minutes. A total of 575 patients were evaluated in the unexposed period and 259 in the exposed. In univariable analysis, there was no significant increase in the proportion of LVO AIS treated with EVT (40.5% vs. 45.6%, unexposed vs. exposed, p=0.17) . In multivariable adjusted mixed-effects model, EVT rates did not change due to software implementation [OR 1.18, p=0.45].

Discussion:
In a multi-center cluster randomized trial, implementation of an automated LVO detection software with care team-wide communication did not significantly alter rates of EVT in patients with LVO AIS.
Abstract WP56: Improvement In Motor And Language Domains Mediates Most Of The Effect Of 24h NIHSS Improvement On Functional Independence
Authors: Pujara Deep , Churilov Leonid , Hassan Ameer E , Abraham Michael G , sitton clark , Duncan Kelsey R , Al-Shaibi Faisal , Shaker Faris , Sundararajan Sophia , Sila Cathy A , Albers Gregory W , Campbell Bruce , Sarraj Amrou
Published: February 2023

Introduction:
Improvement in NIH stroke scale scores on 24h follow-up is considered a key prognostic element after endovascular thrombectomy (EVT). We aimed to evaluate the proportion of effect of 24h NIHSS improvement on mRS 0-2 at 90d mediated through improvement in motor and language domains.

Methods:
From SELECT study, EVT patients with detailed NIHSS components on presentation and 24h follow-up as well as complete mRS on discharge and 90d were selected. Motor improvement was defined as ≥2 point in cumulative arms and legs score or 0 score at 24h and language improvement was defined as ≥1 point in cumulative aphasia and dysarthria scores at 24h. Mediation analysis framework using 4-step method (Figure 1a) was used to evaluate the effect of 24h NIHSS improvement mediated through improvement in motor and language scores.

Results:
Of 192 eligible EVT patients, 176 demonstrated motor deficits and 187 demonstrated language deficits. 24h NIHSS improvement was significantly associated with mRS 0-2 (aOR:1.15[1.07-1.23], p<0.001) - step 1. 24h NIHSS improvement was also significantly associated with motor (aOR:1.77[1.48-2.12],p<0.001) and speech improvement (aOR:1.25[1.16-1.36],p<0.001) - step 2. In the full model, motor (aOR:3.00[1.07-8.46],p=0.037) and speech improvement (aOR:3.15[1.37-7.27],p=0.007) were significantly associated with mRS 0-2, whereas 24h NIHSS improvement was no longer a significant predictor (aOR:1.05[0.96-1.15],p=0.33) - step 3 of figure 1a. Motor improvement mediated 68% and speech improvement mediated 27% of the association of 24h NIHSS improvement with mRS 0-2 (Figure 1b) - step 4.

Conclusions:
Almost all (~95%) of the effect of 24h NIHSS improvement on functional independence (mRS 0-2) was mediated through specific improvement in motor and language domains, suggesting a large role of improvement in motor and language domains in achieving better functional independence. Further studies are needed to confirm the findings.
Abstract WP57: Large-scale Reliability/Validity Assessments And Quantification Of Cognition Within The Imperial College Comprehensive Assessment For Cerebrovascular Disease (IC3): A Novel In-depth, Self-administered, Online Cognitive Tool
Authors: Gruia Dragos C , Combrie Sabia , Coghlin Joseph , Trender William , Hellyer Peter , Kwan Joseph , Banerjee Soma , Hampshire Adam , Geranmayeh Fatemeh
Published: February 2023

Background:
Cognitive difficulties occur in up to 86% of acute stroke cases and persist in a third. There is a growing need for a scalable, cost-effective and in-depth assessment of cognitive function in patients, that enables longitudinal tracking of recovery and better understanding of predictors of long-term cognitive outcomes. This study aims to address this gap by presenting reliability and validity data on a novel self-administered online assessment tool that assesses cognition after stroke.

Method:
This self-administered web-based tool offers an in-depth cognitive profiling through 22 tasks spanning both domain-general (e.g. attention) and domain-specific deficits (e.g. memory, language, visual neglect), together with neuropsychiatric questionnaires. In light of these specifications, the battery has been named IC3 (Imperial College Comprehensive assessment for Cerebrovascular disease;
https://ic3study.co.uk/
)

Results:
We present results outlining the normative ranges for the assessment in 1000+ gender, age and education matched controls and in a modest sample of patients following stroke. Furthermore, we present results showcasing the reliability and validity of the assessment through specificity, sensitivity and test-retest analyses. Finally, we present a novel statistical approach that allows one to tease out motor-driven deficits during response selection, from true cognitive deficits, allowing for a more precise phenotyping of cognition in stroke.

Conclusion:
IC3 is the first assessment to offer in-depth unsupervised cognitive phenotyping of patients following stroke, while also allowing scalable and cost-efficient longitudinal monitoring. It fares well against various reliability/validation metrics and is able to capture cognition in a more precise and scalable manner than currently available assessments, making it an attractive tool for understanding the mechanisms of recovery in a plethora of vascular disorders.
Abstract WP59: Latino Ethnicity Is Associated With Reduced Cognitive Functioning After Stroke Inpatient Rehabilitation
Authors: Garcia James J , Serpas Dylan
Published: February 2023

Brief Introduction:
Stroke is one of the leading causes of disability and mortality in the United States, with higher prevalence and functional burden among Latino communities compared to Whites (García & Warren, 2019). The inpatient rehabilitation milieu provides a unique opportunity to examine ethnic differences in stroke functionality. Yet, little is known regarding the functional outcomes of the inpatient stroke rehabilitation experience of Latinos (Cruz-Flores et al., 2011). Therefore, the current study examined the associations between Latino ethnicity and poststroke outcomes in the context of stroke inpatient rehabilitation.

Methods:
This is a cross-sectional and retrospective analysis of data extracted from an administrative database for years 2005-2016 of 172,937 stroke patients. Data were pooled from inpatient rehabilitation facilities that participated in the secure platform
eRehabData.
Participants included were 1) age 18 or above, 2) had a stroke admitting diagnosis (ICD 9/10 codes 430-438/I60-I69), and 3) self-reported ethnicity as Latino or White. The analytic strategy included two hierarchical regression analyses and one Independent Samples t-test. Ethnicity was dummy coded to examine differences in outcomes between Latino and White stroke patients. Sociodemographic and clinical covariates were entered into block 1 of each separate hierarchical regression model, consistent with previous studies. Block 2 of each model comprised the outcome measures: admission cognitive functioning scores and discharge cognitive functioning scores.

Results:
Latinos had greater BMI and lower age compared to Whites. No ethnic differences in LOS were found. Hierarchical regression analyses controlling for covariates showed that Latino participants (relative to Whites) had lower admission cognitive functioning scores and discharge cognitive functioning scores.

Conclusions:
Ethnic differences were found for Latinos in cognitive functioning at different points throughout stroke inpatient rehabilitation, even after accounting for clinical and sociodemographic covariates. Results are discussed within a framework of social determinants of stroke health for Latinos.
Abstract WP65: A Qualitative Exploration Of Stroke Survivors’ Participation In Physical Exercise And Associated Beliefs And Barriers
Authors: Chau Janita Pak Chun , Liang Surui , Butt Laveeza , Lo Suzanne Hoi Shan
Published: February 2023

Introduction:
Physical activity is a vital component of post-stroke rehabilitation. However, as survivors’ functional abilities or environmental circumstances may impede their participation in physical activity, this qualitative study aimed to investigate their patterns and perceptions of exercise to identify rehabilitation barriers and improve survivor health outcomes.

Methods:
Semi-structured interviews were carried out with fifty stroke survivors recruited by convenience sampling. Participants were asked about their physical limitations post-stroke, past and present activity levels, beliefs regarding physical activity, and desired rehabilitation support. Interviews were transcribed verbatim and thematically analyzed.

Results:
Regarding exercise behaviors, the majority of participants took regular walks and only a minority engaged in targeted exercises for arms or legs. Generally, although survivors recognized the value of post-stroke exercise in improving their health, barriers due to physical limitations and a mismatch between community resources and survivor needs led to suboptimal exercise behaviors. Most participants did not have residential elevators and some reported inconvenience in leaving their homes. Among those with relatively serious physical restrictions, fear of adverse incidents such as falls was common and prevented them from attempting exercise both outside and at home. Moreover, among those who could access community exercise facilities, some felt that the provided equipment did not suit their body types and that they would feel unsafe using them. To boost participation and confidence in exercise, home guidance from rehabilitation care providers and the presence of caregivers or volunteers during physical activity were recommended.

Conclusions:
Sufficient participation in physical exercise remains challenging for stroke survivors due to a variety of physical restrictions and perceived safety concerns. To increase accessibility and encourage more frequent exercise among survivors, it is important to implement home rehabilitation strategies as alternatives to outdoor exercise, and to provide dedicated in-person support to prevent adverse incidents.