bluuebunny/crossref_metadata_2025 huggingface dataset:
Sox9 Accelerates Vascular Aging by Regulating Extracellular Matrix Composition and Stiffness
Authors: Faleeva Maria , Ahmad Sadia , Theofilatos Konstantinos , Lynham Steven , Watson Gabriel , Whitehead Meredith , Marhuenda Emilie , Iskratsch Thomas , Cox Susan , Shanahan Catherine M.
Published: February 2024

BACKGROUND:

Vascular calcification and increased extracellular matrix (ECM) stiffness are hallmarks of vascular aging. Sox9 (SRY-box transcription factor 9) has been implicated in vascular smooth muscle cell (VSMC) osteo/chondrogenic conversion; however, its relationship with aging and calcification has not been studied.

METHODS:

Immunohistochemistry was performed on human aortic samples from young and aged patients. Young and senescent primary human VSMCs were induced to produce ECM, and Sox9 expression was manipulated using adenoviral overexpression and depletion. ECM properties were characterized using atomic force microscopy and proteomics, and VSMC phenotype on hydrogels and the ECM were examined using confocal microscopy.

RESULTS:

In vivo, Sox9 was not spatially associated with vascular calcification but correlated with the senescence marker p16 (cyclin-dependent kinase inhibitor 2A). In vitro Sox9 showed mechanosensitive responses with increased expression and nuclear translocation in senescent cells and on stiff matrices. Sox9 was found to regulate ECM stiffness and organization by orchestrating changes in collagen (Col) expression and reducing VSMC contractility, leading to the formation of an ECM that mirrored that of senescent cells. These ECM changes promoted phenotypic modulation of VSMCs, whereby senescent cells plated on ECM synthesized from cells depleted of Sox9 returned to a proliferative state, while proliferating cells on a matrix produced by Sox9 expressing cells showed reduced proliferation and increased DNA damage, reiterating features of senescent cells. LH3 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3) was identified as an Sox9 target and key regulator of ECM stiffness. LH3 is packaged into extracellular vesicles and Sox9 promotes extracellular vesicle secretion, leading to increased LH3 deposition within the ECM.

CONCLUSIONS:

These findings highlight the crucial role of ECM structure and composition in regulating VSMC phenotype. We identify a positive feedback cycle, whereby cellular senescence and increased ECM stiffening promote Sox9 expression, which, in turn, drives further ECM modifications to further accelerate stiffening and senescence.
Abstract 117: Bleeding Risks for Acute Ischemic Stroke Patients on Serotonergic Antidepressants and Anticoagulation/Dual Anti-Platelet Therapy
Authors: Simmonds Kent P , Chavez Audrie , Ifejika Nneka L
Published: February 2024

Background:
Selective serotonin/serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs) are associated with improved stroke recovery. Some clinicians withhold SSRI/SNRIs over bleeding risk concerns. Our objectives were: 1) Quantify the association between early initiation of SSRI/SNRIs and adverse bleeding events among acute ischemic stroke (IS) patients, 2) Determine bleeding risks among patients receiving anticoagulation (AC) or dual antiplatelet therapy (DAPT), and 3) Evaluate bleeding risks between anti-depressant (AD) classes.

Methods:
Medication naïve first-time IS patients were identified from Electronic Medical Records of 70 healthcare organizations (2003-2023). Patients without ADs were considered “No AD”. Patients started on ADs within 3 months of the indexed stroke were classified as "SSRI/SNRI" or "Other AD" (i.e., Mirtazapine, bupropion, trazodone, or tricyclic ADs). The primary outcome was 1-year risk of major bleeding events (e.g., gastrointestinal/intracranial or shock). Secondary outcomes were hemorrhagic stroke (HS), fall and death. Baseline differences were adjusted for using 1:1 matched propensity scores.

Results:
A total of n=666,150 patients were included [No AD (n=607,278), SSRI/SNRI (n=35,631), Other AD (n=23,241)]. Early use of SSRI/SNRIs (vs. No ADs) was not associated with an increased risk of a major bleed for all patients (n=35,557 matched pairs) or among patients on AC (n=7,672 matched pairs). However, concurrent use of SSRI/SNRIs and DAPT was associated with a 29% increased risk of HS (RR:1.29, 95% CI: 1.11-1.50, n=8,381 matched pairs). Among patients on ADs, bleed risks were higher for use of “Other ADs” vs. "SSRI/SNRIs" (n=21,810 matched pairs).

Discussion:
SSRI/SNRIs treat post-stroke depression, promote functional recovery and are generally safe to start during the early stages of recovery for patients with IS. However, an increased risk of HS should be considered when starting ADs among patients on DAPT.
Abstract 119: Stroke Recovery and Genetic Variation: Main Results of the STRONG Study
Authors: Cramer Steven C , Parodi Livia , Moslemi Zahra , Braun Robynne , Aldridge Chad , Shahbaba Babak , Rosand Jonathan , Holman E. Alison ,   On behalf of the STRONG Study Investigators
Published: February 2024

Introduction:
The STRONG (Stroke, sTress, RehabilitatiON, and Genetics) study performed detailed behavioral phenotyping to evaluate genetic variants in relation to stroke recovery and stress responses.

Methods:
Adults with a new stroke enrolled at 28 US sites were assessed 4 times over 1 year. Three pre-specified gene variants (ApoE-e4, rs6265 (BDNF), & a dopamine polygenic score) were examined for associations with change in grip strength, function (SIS-ADL), mood (PHQ8), and cognition (tMoCA). Seven candidate gene variants (HTTLPR, rs324420, rs4291, rs6265, rs4680, rs53576, rs1360780) were examined for associations with post-stroke trauma, mood, & PTSD. Data were Holm-Bonferroni corrected. Next, genome-wide association studies (GWAS) were performed to identify variants associated with 8 stroke outcomes of interest.

Results:
The 763 enrollees had age 63.1±14.9 yrs; initial NIHSS score 4 [2-9]; 41.2% Female; 69.4% White. Presence of the BDNF rs6265 polymorphism (in 27.1% of patients) was associated with a 0.9 point reduction in 1 yr tMoCA score (p=10^-5). Two of the 7 stress-related gene candidates [rs4291 (ACE) and rs4680 (COMT)] were risk factors linking increased post-stroke trauma with higher 1yr PHQ8 & PTSD scores (p<0.05). In GWAS, 4 of the 8 behavioral outcomes had significant (p<5x10^-8) associations with genetic variants. Change in grip strength (from acute to d90) had the largest number of genome-wide significant (147 at p<5x10^-8) and suggestive (2,541 at p<5x10^-6) associations; variants with p<5x10^-6 were then mapped to corresponding genes and their protein products to construct an interaction network, which had significant enrichment of protein-protein interactions (283 proteins, 69 edges, p=0.008) and which mapped (FDR<0.05) to multiple gene ontology biological processes pertaining to the nervous system, including nervous system development, neurogenesis, and neuron differentiation.

Conclusions:
Stroke recovery occurs across many dimensions and so benefits from detailed characterization over time. Building on such assessments, current results from candidate genetic variants and GWAS provide insights into the biology of stroke recovery and inform therapeutic targets for promoting improved stroke recovery.
Abstract 124: Pre-Stroke Aspirin Use Does Not Impact Small Subcortical Stroke Size: A Secondary Analysis of the SPS3 Trial
Authors: Liew Sabrina , Shu Liqi , Yaghi Shadi , Goldstein Eric D
Published: February 2024

Introduction:
The use of pre-stroke aspirin is associated with smaller stroke size in first-time stroke related to large vessel occlusion. However, it is unknown whether pre-stroke aspirin use impacts stroke size for an acute small subcortical infarct (SSI). We hypothesized that pre-stroke aspirin use would be associated with a smaller sized SSI.

Methods:
We performed a secondary analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) dataset which enrolled between 2003 and 2007. We included participants ≥ 55 years old with brain-MRI confirmed SSI being ≤ 20 mm in maximal diameter on diffusion weighted imaging. Stroke size was determined retrospectively by the study team on the index event brain MRI. Pre-stroke medications were recorded at the time of enrollment. Chi-squared and student’s T test were used for categorical and continuous variables, respectively. Binary logistic regression models were fitted for likelihood ratios.

Results:
Of the 3020 participants enrolled in SPS3, a total of 2183 met inclusion criteria: 663 with pre-stroke aspirin monotherapy and 1520 without pre-stroke antithrombotic use, Table 1. Those with aspirin use were older with a higher incidence of diagnoses of hypertension, hyperlipidemia, and diabetes mellitus, though otherwise sex, and tobacco use did not differ. The mean maximal stroke width, trended towards, but was not statistically impacted by pre-stroke aspirin use [pre-stroke aspirin: 11.8 (4.1) mm vs 11.4 (4.1) mm,
p
=0.065]. After adjustment for significant variables, pre-stroke aspirin use did not impact the odds of a larger infarct size (OR 0.779, 95%CI 0.615-1.04,
p
=0.092).

Conclusion:
Despite those with pre-stroke aspirin use having more vascular risk factors, its use did not impact stroke size amongst those with an acute SSI enrolled in the SPS3 trial.
Abstract 131: Association Between Left Ventricular Injury Detected by Cardiac MRI and Incident Ischemic Stroke: The Multi-Ethnic Study of Atherosclerosis
Authors: Sharma Richa , Hansen Spencer , Merkler Alexander E , Lima Joao , Longstreth W T
Published: February 2024

Background:
The association between left ventricular injury (LVI) detected by cardiac magnetic resonance imaging (CMR) and the risk of a subsequent ischemic stroke is unknown.

Methods:
We studied stroke-free participants in the Multi-Ethnic Study of Atherosclerosis study who underwent a steady-state free precession CMR at Exam 5 (2010-2012). The exposure of interest was LVI defined by either LV ejection fraction (EF) < 50% or circumferential strain
>
-10 in any LV apical wall. The primary outcome was incident ischemic stroke. We performed Cox proportional hazard analysis to model the association between LVI and incident ischemic stroke, adjusting for demographic and clinical covariates.

Results:
The analytic sample consisted of 2,584 participants (n=302 or 11.7% with LVI, n=2,282 or 88.3% without LVI). There were a total of 18 ischemic stroke events among those with LVI (6%) and 65 among those without LVI (3%). Participants with LVI were significantly older, male, Black, had higher BMI, and lower HDL. Participants with LVI were more likely to have diabetes, tobacco use, and atrial fibrillation (24% versus 14%, p<0.001). There was no significant difference in history of cardiovascular disease events (6% versus 4%, p=0.143). LVI was significantly and independently associated with incident ischemic stroke (adjusted hazard ratio 1.80, 95% C.I. 1.04-3.12). When participants were stratified into 3 mutually exclusive groups of no LVI, LVEF
>
50% and LV apical circumferential strain < -10, and LVEF < 50% and LV apical circumferential strain
>
-10, the hazard of incident ischemic stroke was significantly higher for each of the two latter groups compared to the no LVI group (log-rank p-value=0.003;
Figure 1
).

Conclusion:
LVI identified by CMR is a significant, independent predictor of incident ischemic stroke. LV apical circumferential strain
>
-10% may be a novel and quantitative stroke risk factor. Further studies are needed to validate these CMR biomarkers of stroke risk.
Abstract 132: Disability and Enrollment in Secondary Stroke Prevention Trials: Evidence for a New Paradigm of Inclusion
Authors: de Havenon Adam H , Viscoli Catherine , Kernan Walter N , Kleindorfer Dawn O , Robinson David , Becker Christopher , Sucharew Heidi , Sheth Kevin N
Published: February 2024

Background:
Ischemic stroke secondary prevention trials have disproportionately enrolled participants with mild or no disability. The impact of this skew on trial event rates is unclear.

Methods:
We included participants with ischemic stroke in two secondary stroke prevention trials, PRoFESS and IRIS. The exposure was functional status at entry, defined as modified Rankin Scale (mRS) 0 vs. 1-2 vs. >2. The primary outcome was recurrent stroke (ischemic or hemorrhagic). The secondary outcome was a composite of major adverse cardiovascular events (MACE=stroke, myocardial infarction, heart failure, and vascular death).

Results:
The cohorts had 20,384 participants from PRoFESS and 3,374 from IRIS. The mean duration of follow-up was 2.4 years in PRoFESS and 3.8 years in IRIS. The rate of recurrent stroke in the mRS categories (0 vs. 1-2 vs. >2) was 7.2%, 8.7%, and 10.6% in PRoFESS and 6.2%, 9.1%, and 11.9% in IRIS (both p≤0.001). The rate of MACE in the mRS categories was 10.1%, 12.2%, and 17.3% in PRoFESS (p<0.001) and 10.6%, 13.3%, and 15.3% in IRIS (p=0.030). In both trials we saw consistent increases in the hazard ratio for recurrent stroke (Table 1) and MACE (Table 2) across mRS categories, after adjusting for potential confounders. There was no evidence that treatment effects differed across mRS categories (mRS by treatment interaction p>0.4).

Conclusion:
Secondary stroke prevention trial participants with higher levels of baseline disability have increased rates of recurrent stroke and MACE. By enrolling participants across the full range of disability, stroke trials would observe more recurrent stroke events, enhance statistical power, and improve generalizability of results.
Abstract 139: Regional Disparities in Mechanical Thrombectomy Utilization for Treatment of Acute Ischemic Stroke in the United States
Authors: Maqsood Hamza , Kwok Chun Shing , Gillani Syed A , Suri Fareed K , Shah Qaisar A , Siddiq Farhan , Gomez Camilo R , Qureshi Adnan I
Published: February 2024

Background:
A current national priority is to understand geographic disparities in mechanical thrombectomy (MT) provision for patients with acute ischemic stroke (AIS). We examine variation in rates of MT by geographic region and urban-rural areas to identify utilization disparities across the United States.

Methods:
The state-specific annual incidence of AIS in 2019 was determined using data from the Global Burden of Disease Collaborative Network. We determined the number of patients who were admitted with AIS due to thrombosis or embolism of anterior circulation arteries and those who received MT in a particular region/state based on the State Inpatient Database of NIS. The National Inpatient Sample data were used to create national weighted estimates of the size of subject populations, age at admission, length of stay, and discharge status.

Results:
In the United States, approximately 28,165 MT were performed in 2019, representing 4% of the AIS population. In large central metropolitan areas, the proportion of thrombectomies performed to the AIS patient population was significantly higher than the national estimate (4.34%, P < 0.001); small metropolitan areas and rural settings (micropolitan and noncore) had significantly lower proportions of MT-treated patients with 3.2% and 2.9%, respectively (P < 0.001), when compared with the national estimate. West region had significantly higher proportions of MT-treated patients with 4.3%, compared with the national estimate (P < 0.001), whereas South region had significantly lower proportions with 3.8% (P < 0.001).

Conclusions:
We found prominent regional disparities in the utilization rates of MT in acute ischemic stroke patients in the United States, which may have implications for Regional Stroke Destination Plans in Rural, Suburban, and Urban Communities.
Abstract 140: Sleep-Disordered Breathing Shortly After Stroke Does Not Predict Post-Stroke Fatigue at 3-months
Authors: Becker Christopher J , Lisabeth Linda D , Kwicklis Madeline , Shi Xu , Chervin Ronald D , Case Erin , Brown Devin L
Published: February 2024

Background:
Post-stroke fatigue (PSF) is a common and often disabling symptom, the causes of which are poorly understood. Sleep-disordered breathing (SDB) is highly prevalent among stroke survivors, and can cause fatigue. We examined whether SDB measured shortly after stroke predicted PSF at 3-months, and thus whether SDB might represent an intervention target for the treatment/prevention of PSF.

Methods:
Ischemic stroke (IS) patients within the Brain Attack Surveillance in Corpus Christi (BASIC) project were identified through active and passive surveillance, and were offered SDB screening with a well-validated cardiopulmonary sleep apnea testing device. The primary exposure was the respiratory event index (REI; sum of apneas plus hypopneas per hour of recording), measured shortly after stroke. The primary outcome was PSF, measured 3-months post-stroke, using the SF-36 vitality scale. Linear regression was used to evaluate the association between baseline REI and 3-month PSF, adjusting for clinical and sociodemographic factors listed in the Table, which were obtained from chart review and interviews.

Results:
A total of 355 IS participants completed baseline SDB screening and 3-month PSF assessments from May 2016 to December 2019. Participants were 44% female, 60% Mexican American (MA), and had a median NIHSS of 2 (IQR: 1-5). Multivariable regression model results are presented in the Table. No association between baseline REI and 3-month PSF was observed in unadjusted (β=0.95, 95% CI=-1.16, 3.05) or fully adjusted models (β=0.66, 95% CI=-1.40, 2.73). In the fully adjusted model, female sex and depression were associated with greater fatigue, while older age and MA ethnicity were associated with less fatigue.

Conclusions:
SDB in the immediate post-stroke period, at least in this predominantly MA sample, does not predict PSF at 3-months. Though identification and treatment of post-stroke SDB may be important, these efforts are unlikely to impact PSF.
Abstract 147: Novel Inflammatory and Pro-Thrombotic mRNA Pathways Associated With Worse 3-month Outcome After Intracerebral Hemorrhage
Authors: Wright W. S , Langefeld Carl D. , Comeau Mary , Hawkins Greg , Flaherty Matthew , Gilkerson Lee , Howard Tim D. , James Michael L , Kittner Steven J , Mehndiratta Prachi , Roh David , Vahidy Farhaan , Testai Fernando , Bagga Ranjit , Thornton James B. , Cortes Juan Camilo , Menzies Lauren , Nobel Lisa , Wechsler Paul , Xia Christina , Woo Daniel , Demel Stacie
Published: February 2024

Background:
Intracerebral hemorrhage (ICH) has the highest disability among stroke survivors. The
Recovery and Outcomes from Stroke (ROSE) study
(U01NS100417) utilized RNA sequencing (RNAseq) to identify biomarkers associated with poor outcome at 3 months.

Methods:
Supratentorial, non-moribund, ≥ 18 years of age, spontaneous ICH patients were prospectively recruited in a multi-center study. Whole blood was obtained at baseline (<15 days; RNA PAXgene tubes, Qiagen). 3-month outcomes were determined by modified Rankin Scale (mRS) 0-3 (good) vs 4-6 (poor). RNAseq libraries were constructed using the Illumina TruSeq Stranded Total RNA kit with Ribo-Zero, sequenced on an llumina NovaSeq 6000 platform using 1 x100 bp single end reads to generate 25-30 million reads at >90% >Q30 reads. Differential expression was tested using DESeq2 (negative binomial), adjusting for sequencing batch, age, sex, race, ICH volume, intraventricular hemorrhage, presenting Glasgow Coma Scale, and lobar vs non-lobar location. Pathway analyses and protein-protein interactions were computed on a set of genes (P < 0.0001) using STRING, Cytoscape, MCODE, and Reactome.

Results:
We analyzed baseline blood samples from 278 patients (N = 156 vs 122; good vs poor outcomes at 3 months). Multiple pathways were associated with poor outcome, including those involved in clot formation and cell-cell/cell-matrix interactions (not shown). The statistically most significant pathway was observed for transcripts involved in neutrophil activation and degranulation.

Conclusion:
Variation in mRNA expression pathways associated with inflammation, coagulation and cellular interactions were associated with poor outcome after controlling for severity measures.
Abstract 151: GFAP Measurements for Rapid Prehospital Identification of Intracranial Hemorrhage in Patients With Acute Coma
Authors: Zylyftari Sabina , Kalra Love-Preet , Blums Kristaps , Barthelmes Stephan , Humm Sebastian , Baum Hannsjoerg , Meckel Stephan , Heilgeist Andreas , Luger Sebastian , Foerch Christian
Published: February 2024

Background:
Prehospital triage and treatment of patients with acute coma is challenging for rescue services, as the underlying pathogenetic conditions are highly heterogenous and difficult to assess. Glial fibrillary acidic protein (GFAP) has been recently identified as a biomarker of intracerebral hemorrhage. The aim of this study was to test the diagnostic value of a GFAP point-of-care(poc) device to rapidly differentiate intracranial hemorrhage from other causes of acute coma (including seizures, metabolic disorders, cardiovascular disorders, and intoxication) in the prehospital phase.

Methods:
Patients who were admitted to the emergency department due to acute coma (Glasgow Coma Scale scores between 3-8) were enrolled prospectively. Blood samples were collected already in the prehospital phase. Plasma GFAP measurements were performed on the i-STAT Alinity® (Abbott) device (duration of analysis 15 min). The primary endpoint was the final diagnosis at hospital discharge.

Results:
95 patients were enrolled (mean age 64±20 years, 43% female). GFAP concentrations were strongly elevated in patients with a primary cerebral cause of coma compared to primary non-cerebral causes (p<0.001). The GFAP concentrations (mean±SD in pg/mL) according to final diagnosis were as follows: intracerebral hemorrhage 4840±4500 (n=15), subarachnoid hemorrhage 4858±4662 (n=11), subdural or epidural hematoma 3462±4005 (n=4), ischemic stroke 992±2857 (n=12), seizure 45±21 (n=11), cardiovascular or metabolic disorder 258±888 (n=29), intoxication 30±2 (n=6), psychogenic stupor 29±0 (n=2); n=5 patients had missing diagnoses. GFAP values over 1000 pg/ml indicated a primary cerebral cause of coma with 100% certainty (hereof, 86% had intracranial hemorrhage).

Conclusion:
Increased GFAP plasma values in patients with acute coma identify a primary cerebral cause of coma (mostly intracranial hemorrhage) with very high diagnostic accuracy. Patients with primary non-cerebral causes of coma showed overall low GFAP concentrations. Prehospital GFAP measurements on a poc platform may allow rapid stratification according to the underlying cause of coma by rescue services. This could have major impact on triage and management of these critically ill patients.
Abstract 33: An Innovative Digital Health Approach to Enhance Patient Engagement in Stroke Care
Authors: Leonhardt-Caprio Ann M , Kelly Adam G , Lempke Stephanie
Published: February 2024

Introduction:
Patient engagement (PE) is a crucial aspect of health management shown to improve adherence and outcomes. For patients with ischemic stroke (IS) and transient ischemic attack (TIA) PE holds significant value. Novel ways to engage IS/TIA patients and deliver personalized education may enhance knowledge, satisfaction, and adherence while potentially reducing recurrent stroke.

Purpose:
Develop and implement a stroke-specific 90-day digital health PE platform for IS/TIA patients discharged (DC) home from a Comprehensive Stroke Center (CSC). Utilizing the Twistle
TM
digital platform the initiative focuses on patient education and adherence.

Methods:
An expert panel (digital health operations, vascular neurologist, stroke-certified nurse practitioner) designed a 90-day program with 21 modules emphasizing education, adherence, communication, and 90-day mRS self-assessment. A pre-implementation survey assessed confidence to prevent stroke and knowledge of personalized risk factors, lifestyle modification, and medication in 14 IS/TIA patients (Mdn 21 days from DC), with 11 responses (73.3%). After pilot testing with 2 patients and feedback incorporation, 10 more patients were enrolled. A patient engagement and satisfaction survey was administered on day 20.

Results:
Assessment determined the program was feasible and compared pre-implementation and 20-day survey responses from participants (response rate 6/9). Post-implementation outcomes showed improved patient knowledge and confidence. Patients agreeing/strongly agreeing to having lifestyle modification knowledge increased from 64.6% (n=11) to 83.4% (n=6). Confidence in preventing another stroke/TIA rose from 27.3% (n=11) to 66.7% (n=6). Participants reported heightened engagement through digital messages (83.3%, 5/6), while one respondent (16.7%) remained neutral.

Conclusions:
Initial findings underscore the potential of digital health, delivered through platforms like Twistle
TM
, to enhance patient engagement and confidence post-IS/TIA. The program's successful launch suggests promise for expansion at the CSC and potentially across additional health system hospitals. The initiative holds potential for enhancing patient outcomes and well-being.
Abstract 38: Temporal Changes in Intracranial Arterial Diseases: A Longitudinal High-Resolution Vessel Wall Imaging Analysis
Authors: Kang Dong-Wan , Kim Do Yeon , Kim Jonguk , Kim Nakhoon , Ko Yoona , Cha Jeongmin , Song Jae W , Kim Jun Yup , Baik Sung Hyun , Jung Cheolkyu , Han Moon-Ku , Bae Hee-Joon , Kim Beom Joon
Published: February 2024

Introduction:
Temporal changes of intracranial arterial disease (ICAD) in patients with ischemic stroke in high-resolution vessel wall imaging (HR-VWI) have not been elucidated.

Methods:
We recruited consecutive ICAD-related ischemic stroke patients admitted between June 2016 and June 2019 and had subsequent HR-VWI follow-ups. On HR-VWI, we manually segmented the lumen area (LA), total vessel area (TVA), and enhancing area (EA) of the culprit lesion's most stenotic part in the perpendicular section on T1-weighted, proton density, and post-contrast T1-weighted sequences. We defined the area stenosis as [1-LA/TVA]х100 (%) and the enhancing proportion as EA/TVAх100 (%). Enhancement ratio of the enhancing lesion was also quantified. Three raters independently quantified the imaging using ITK-SNAP with acceptable inter-rater reliability.

Results:
A total of 208 patients (age 57±14, male 58%) with 469 HR-VWIs (2-6 scans per patient) were included. The causes of ICAD were atherosclerosis (69%), dissection (24%), vasculitis (3%), moyamoya disease (1%), and other causes (2%). The median follow-up duration was 9.0 months (interquartile range: 3.9-13.2 months), and the maximum follow-up duration was 41.3 months. Among patients with atherosclerosis, area stenosis aggravated, stable, and improved in 7%, 77%, and 16%, respectively, with an overall rate of 0.23 ± 0.07% improvement per month. Among patients with dissection, area stenosis aggravated, stable, and improved in 2%, 49%, and 49%, respectively, with an overall rate of 2.11 ± 0.26% improvement per month (Figure,
P
-for-difference < 0.01). The temporal changes of the enhancing proportion and enhancement ratio were different between atherosclerosis and dissection (Figure,
P
< 0.01).

Conclusions:
ICAD lesions had dynamic changes over time; the temporal changes of atherosclerosis and dissection are distinct. Serial HR-VWI can offer insights for a more accurate diagnosis of the underlying pathologies of ICADs.
Abstract 45: Poor Prediction of Stroke Mimics Using Validated Stroke Mimic Scales in a Large Academic Telestroke Network
Authors: Chhabra Nikita , English Stephen , Butterfield Richard J , Zhang Nan , Hanus Abigail , Basharath Rida , Miller Monet , Demaerschalk Bart M
Published: February 2024

Introduction:
Telestroke enables timely and remote evaluation of patients with acute stroke syndromes. However, stroke mimics represent more than 30% of this population. Given the resources required for management of suspected acute ischemic stroke, several scales have been developed to help identify stroke mimics. Our objective was to externally validate four mimic scales (Khan Score [KS], TeleStroke Mimic Score [TS], simplified FABS [sFABS], and FABS) in a large, academic telestroke network.

Methods:
This is a retrospective, IRB exempt study of all patients who presented with suspected acute stroke syndromes and underwent video evaluation between 2019-2020 at a large academic telestroke network. Detailed chart review was conducted to extract both the variables needed to apply the mimic scales the final diagnosis confirmed by final imaging and discharge diagnosis (cerebral ischemic vs stroke mimic). Overall score performance was assessed by calculating area under curve (AUC). Youden cutpoint was established for each scale and used to calculate sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy.

Results:
A total of 1043 patients were included in the final analysis. Final diagnosis of cerebral ischemia was made in 662/1043 patients (63.5%) and stroke mimic was diagnosed in 381/1043 patients (36.5%). To predict stroke mimic, TS had the highest AUC (68.3) and PPV (73%); KS had the highest accuracy (68.6%), sensitivity (86.6%) and NPV (61.5%); and FABS had the highest specificity (54.8%) (Table 1).

Conclusions:
While each scale offers unique strengths, none was able to identify stroke mimics effectively enough to confidently apply in clinical practice. There remains need for significant clinical judgment to determine the likelihood of stroke mimic at presentation.
Abstract 56: Temporal Blood Exposure in Neural Organoids Stimulates Dynamic Astrocyte Reactivity
Authors: Seah Carina , Schuldt Braxton R , Vicari James , Lebakken Connie , Kellner Christopher P
Published: February 2024

Introduction:
The impact of intracerebral hemorrhage (ICH) and timing of surgical evacuation on brain cell types is poorly understood. Here, we identify cell type specific responses to blood exposure in an organoid model of ICH using single cell transcriptomics.

Methods:
Human organoids consisting of excitatory/inhibitory neurons, neural progenitor cells (NPC), astrocytes, pericytes, and microglia were generated from induced pluripotent stem cells and treated with 5% blood for 6 or 24 hours. Organoids were dissociated and sequenced (scRNAseq). scRNAseq alignment, filtering, and analysis was performed using cellranger, SoupX, Scrublet, and Seurat in R to cluster and identify the cell type composition of organoids. Associations of expression to blood exposure were conducted with mixed-effect linear models. Significance was determined using Benjamini-Hochberg multiple testing correction (FDR <5%). Pathway enrichment was performed with FUMA at FDR<5%.

Results:
We resolved excitatory and inhibitory neurons, NPCs, astrocytes, pericytes, epithelial cells, fibroblasts, and microglia with cell type-specific responses to blood. Long exposure to blood induced significant transcriptomic responses, whereas short exposure did not. Astrocytes were the most reactive cell type to blood exposure, and upregulated pathways included proliferative and catabolic processes. Fibroblasts and epithelial cells showed the most downregulated pathways, including impairment of interferon signaling pathways and metabolism.

Conclusion:
Blood exposure induces transcriptomic changes in a temporal and cell type specific manner. Longer exposure to blood induces higher reactivity, and such reactivity is especially mediated by astrocyte upregulation of catabolic and proliferative processes. These results suggest that astrocytes may mediate cerebral response to blood in the setting of ICH, and reinforce early evacuation of ICH as a means to mitigate cellular reactivity.
Abstract 69: Epigenetic Age and Brain Health Events: Findings From the Health and Retirement Study
Authors: Rivier Cyprien , Szejko Natalia , Renedo Daniela , de Havenon Adam H , Sheth Kevin N , Gill Thomas M , Falcone Guido J
Published: February 2024

Introduction:
It is increasingly recognized that chronological age provides an incomplete assessment of true biological age. Epigenetic clocks use DNA methylation data to estimate biological age more accurately. We hypothesize that brain health events (BHe) lead to epigenetic age acceleration and that, conversely, accelerated epigenetic age leads to higher risk of BHe.

Methods:
We conducted a 3-stage epigenetic study within the Health and Retirement Study (Figure). In 2016, participants provided blood samples and methylation and genomic data was generated. Epigenetic age was calculated as the average of thirteen epigenetic clocks that used different combinations of methylation data. BHe was a composite of stroke, dementia and late-life depression. Stage 1 entailed testing for association between BHe prior to 2016 (exposure) and epigenetic age (outcome). Stage 2 entailed testing for association between epigenetic age (exposure) and BHe occurring after 2016 (outcome). Stage 3 entailed testing for causal associations using Mendelian Randomization (MR).

Results:
Results are summarized in the Figure. Out of 4,018 participants with epigenomic data, 2,221 (55%) had a history of BHe before 2016. A history of BHe was associated with an older epigenetic age (beta 0.05, SE 0.01; p<0.01). Of the 3,047 study participants with available follow-up data, 1,018 (33%) developed a BHe over a mean follow up of 4 years. Epigenetic age acceleration was associated with higher odds of BHe (OR 1.57, [1.22-2.01]). Causal associations estimated via MR analyses confirmed both results.

Conclusion:
A history of BHe was associated with epigenetic age acceleration and, conversely, epigenetic age acceleration was linked to a higher risk of brain health events. MR analyses suggest that these associations are causal. These results indicate that more nuanced strategies for ascertaining biological age are needed in stroke research and point to epigenetic clocks as a promising tool for this purpose.
Abstract 7: Scrambler Therapy for Treatment of Post Stroke Pain
Authors: Stowell Campos Robert , Lawrence Erin , Merbach Dawn M
Published: February 2024

Objective:
Infarcts involving sensory pathways can result in a post-stroke pain syndrome that is often refractory to traditional medical therapy. Scrambler Therapy (ST) is a noninvasive electroanalgesia device effectively used to treat peripheral neuropathy; however, data is scarce regarding its use in the central nervous system. In this pilot, we evaluate the efficacy of ST to treat post-stroke pain syndromes.

Methods:
Twenty patients with a history of stroke resulting in contralateral pain were enrolled and randomized to receive ST or Sham as an adjunct to their current medication regimen. Participants underwent 5 consecutive sessions, each lasting 40 minutes. Pain scores were recorded at baseline, as well as before and after each session using a Numeric Rating Scale (0-10). The study was double-blinded to both the participant and operator. Following treatment, pain scores were collected weekly for 4 weeks. Student’s t tests were used to compare scores at: baseline, immediately post-treatment #5, and at 4 week follow-up, between groups as well as the change in pain score between individuals.

Results:
To date, 15 patients have been enrolled and completed the intervention; 10 have completed longer-term follow-up. The average age of the cohort was 57.8 years; 47% were male; 53% black; and the average time from stroke was 26 months. Participants randomized to ST (n=7) had a mean pain score of 6.52 at baseline; the Sham group (n=8) had a mean score of 5.83. The ST group had a mean change from initial score to score after 5 days of treatment of -4.17 (SD 2.64), while the Sham group had a mean change in score of -1.03 (SD 1.42). For patients completing follow-up, the ST group (n=5) saw a mean change pain score from baseline to follow-up of -3.37 (SD 1.71). The Sham group (n=5) a mean change of -0.37 (SD 0.34). Differences in change in score were significant between groups at both time points (p=0.01 and 0.005 respectively).

Conclusion:
There is a significant difference in both acute and longer-term pain reduction for patients with post-stroke pain who undergo treatment using ST compared to Sham that suggests it may be an effective treatment option. Larger studies are needed to evaluate confounders such as stroke location, time from stroke, and concomitant treatment with medications.
Abstract 71: Brain Health Outcomes in Sexual and Gender Minority Groups
Authors: Huo Shufan , Rivier Cyprien , Clocchiatti-Tuozzo Santiago , Renedo Daniela , Sunmonu N. Abimbola , de Havenon Adam H , Sheth Kevin N , Falcone Guido J
Published: February 2024

Background:
There is mounting evidence that sexual and gender minority (SGM) groups experience health disparities, but research on brain health status of this underrepresented group is limited. We evaluated whether SGM persons are at higher risk of adverse brain health outcomes compared to cisgender heterosexual (non-SGM) individuals.

Methods:
We conducted a cross-sectional study in the All of Us Research Program, a population study focused on health disparities enrolling 1 million Americans. We used baseline questionnaires to identify participants from sexual minorities (non-straight e.g., gay, lesbian, bisexual) and gender minorities (gender identity different from sex assigned at birth). We further divided gender minorities into gender diverse (e.g., non-binary) and transgender. The primary outcome was a composite of stroke, dementia, and late-life depression. In secondary analyses, we analyzed SGM subgroups and diseases separately. We used multivariate logistic regression to assess the link between SGM groups and brain health outcomes.

Results:
We included 393,041 participants (mean age 51, female sex at birth 62%), of whom 39,632 (10%) belonged to SGM groups. Of these, 4,431 (1%) belonged to a gender minority (2,212 [50%] gender diverse and 2,219 [50%] transgender) and 38,528 (10%) to a sexual minority. Full results are shown in the Figure. Compared to non-SGM, SGM individuals had 19% higher odds of the brain health composite outcome (OR 1.19, 95%CI 1.13-1.25). These results were consistent across all SGM subgroups (p<0.05). When assessing individual diseases, all SGM groups had higher odds of late-life depression, all SGM except transgender persons had higher odds of dementia, and gender minority groups had higher odds of stroke.

Conclusion:
In a large US population study, SGM individuals had a higher rate of adverse brain health outcomes. Further research should explore the structural causes of inequity to advance inclusive and diverse neurological care.
Abstract 92: Impacts of a Multidisciplinary Brain Heart Team on Patent Foramen Ovale Closure in Patients With Cryptogenic Stroke
Authors: Lee Angus , Han SeungYong , Ly An , Gaffney Denise , Ajani Zahra , Cheng Pamela , Taleb Shayandokht , Le Duy , Pyo Stella , Sangha Navdeep S
Published: February 2024

Background:
The AHA/ASA 2021 Secondary Stroke Prevention Guideline recommends a joint decision by neurology and cardiology for patent foramen ovale (PFO) closure. The impact of a Brain Heart Team (BHT) consisting of interventional cardiologists and vascular neurologists to evaluate PFO closure is unclear. We analyzed whether a BHT implementation led to more guideline recommended PFO closures based on Risk of Paradoxical Embolism (RoPE) score and PASCAL categories across a 15-hospital system.

Methods:
Data were collected retrospectively between 1/2016 - 2/2023. Baseline demographics, risk factors, method of shunt identification, high-risk shunt features, post PFO atrial fibrillation and stroke rates, RoPE score and PASCAL categorization were abstracted. Non-BHT was defined as absence of vascular neurology involvement. Appropriate PFO closure was defined as RoPE score
>
7 and/or PASCAL categories of possible/probable. Chi-squared and t-test were used.

Results:
Of 174 patients, 108 (62%) were identified as BHT and 66 (38%) as non-BHT. There were no differences in baseline risk factors between BHT and non-BHT besides hyperlipidemia (28.7% vs 53% p < .002) and smoking history (12% vs 31.8% p < .003). BHT patients were younger at age of diagnosis and PFO closure (44.8 yrs ±1.7 vs 56 yrs ±1.2 p=0.003 and 44.7 yrs ±1.9 vs. 56 yrs ±1.3 p=0.004 respectively). There were differences in race/ethnicity (Table 1). More BHT patients had possible/probable PASCAL vs non-BHT (101 [93.5%] vs 44 [66.7%], p <0.001). Patients in BHT had higher mean RoPe scores (7.34 ± 1.55 vs 6.06 ± 2.02 p <0.001). More patients in BHT had a RoPE score
>
7 (77 [71.3%] vs 26 [39.4%] p <0.001). There were no differences in atrial fibrillation (5 [4.6%] vs 5 [7.6%] p = 0.635) or stroke after PFO closure (2 [1.9%] vs 2 [3%] p = 1).

Conclusion:
Implementing a multi-disciplinary approach with a Brain Heart Team leads to more guideline based PFO closures in cryptogenic strokes based on PASCAL and RoPE scores.
Abstract 99: Association of Life Essential 8 Score With Major Vascular Outcomes. Results of the Hispanic Community Health Study/Study of Latinos
Authors: Trifan Gabriela , Wu Donghong , Elfassy Tali , Gallo Linda , Sotres-Alvarez Daniela , Massera Daniele , Thyagarajan Bharat , Garcia-Bedoya Olga , Pirzada Amber , Daviglus Martha L , Testai Fernando
Published: February 2024

Background:
The “Life’s Essential 8” (LE8) score is a new tool to determine cardiovascular health (CVH). This includes diet, physical activity, nicotine exposure, sleep duration, body mass index, blood lipids, blood glucose, and blood pressure levels. Here we investigated the association of LE8 with incident major adverse cardiovascular events (MACE) among Hispanic/Latino adults living in the US.

Design/Method:
Baseline characteristics (n=13,956) of HCHS/SOL participants were determined between 2008 and 2011. Annual follow-up interviews were conducted from inception until 2016 to determine outcomes of interest. Hospital records were reviewed and incident MACE, defined as the composite of incident stroke, myocardial infarction, or heart failure, was adjudicated using standard criteria. LE8 scores (range 0 to 100, with higher scores denoting better CVH) were determined using published definitions. Incident rate ratios (IRR) of MACE across LE8 (modeled in 20-points increments) were determined using Poisson regression models and adjusting for baseline characteristics. Analyses were weighted for complex survey design and non-response.

Results:
The mean age (95% CI) at baseline was 40.7 (40.2-41.2) years and 60.6% were females. The mean LE8 score was 68.5 (68.0-69.1). Compared to females, males achieved higher scores in diet (44.9 vs. 36.1, P<0.001), physical activity (82.1 vs. 69.3; p<0.001), and body mass index (60.1 vs. 56.9; p<0.001) and lower scores in nicotine exposure (65.0 vs. 77.1; p<0.001), blood lipids (59.4 vs. 65.1; p<0.001), blood pressure (70.4 vs. 77.5; p<0.001). A total of 181 outcomes occurred during the mean follow-up of 6.8 (6.8-6.9) years. In the fully adjusted model, higher LE8 was associated with a lower incidence of MACE (IRR 0.47, 95% CI 0.30-0.74 for all; IRR 0.44, 95% CI 0.23 to 0.84 in males; IRR 0.49, 95% CI 0.28-0.85 in females).

Conclusion:
Among Hispanic/Latino adults, better CVH, quantified using LE8, is associated with a lower incidence of stroke, myocardial infarction, or heart failure.
Abstract HUP12: Underrepresentation Of Racial And Ethnic Minorities In Stroke Clinical Trials
Authors: Izeogu Chigozirim , Bhojwani Manish , Ahmed Mariam , Chang Kelly , Mehta Amol , Ibrahim Lamya , Rocha Eva , Jones Erica , Ifejika Nneka L , Gonzales Nicole R , Sharrief Anjail Z
Published: February 2024

Background:
Stroke impacts Black and Hispanic individuals disproportionately compared to White individuals. Equitable inclusion in stroke research for disproportionately affected populations is critical for addressing stroke inequities. Prior literature has reported a lack of racial diversity in acute stroke trials, but data are lacking for trials conducted across the stroke care continuum.

Methods:
We performed a comprehensive review of completed trials registered from January 1, 1990, to April 20, 2023, in the ClinicalTrials.gov registry. Trials for stroke treatment in hyperacute, acute, and post-acute care settings were included if they were at least partially conducted in the U.S., enrolled ≥ 50 participants aged 18 and older, and published their results in a peer-reviewed journal available on PubMed or Embase.

Results:
2461 trial records were retrieved, of which 69 stroke trials were included and are reported in this analysis. Overall, 34 of 69 trials (49%) included data on some racial or ethnic demographics in the primary manuscript. For trials conducted exclusively in the U.S., 20 of 30 trials (67%) reported data on race. Among international trials which also included the U.S., 14 of 39 trials (36%) reported data on race. Among trials exclusively conducted in the U.S., 74% of study participants were white. Among trials conducted exclusively in the U.S., 57% of trials funded by government reported race, whereas, 71% of trials funded by industry reported on race.

Conclusion:
This review shows under-reporting of race, ethnicity, and other sociodemographic data in stroke trials across the care continuum. When race and ethnicity are reported, most studies show over-presentation of White individuals, especially considering the disproportionate burden of stroke in Black and Hispanic groups. There is an urgent need to develop and implement strategies to increase diversity in stroke clinical trials to effectively understand and address inequities in stroke care and outcomes.
Abstract HUP17: Outcome Of Decompressive Hemicraniectomy Correlated With Age: An Analysis Of Nationwide Readmission Database (nrd) 2016-2019
Authors: Geiser Rachel I , Pico Annie , Pietz Daniel , Nosova Kristin , Kelbert James , Bina Robert
Published: February 2024

Introduction:
Decompressive hemicraniectomy (DHC) is recommended in adults 60yrs and younger to improve survival and functional benefits in patients experiencing malignant unilateral MCA stroke with neurological decline after 48 hours. However, the AHA/ASA guidelines are less clear regarding the mortality benefit for elderly patients, and there is a paucity of data on the correlation of age and outcomes after DHC.

Objective:
To correlate age with mortality and length of stay (LOS) after DHC for malignant unilateral MCA stroke.

Methods:
Adult patients with unilateral MCA stroke were identified in NRD 2016-2019 using ICD-10 codes. Patients who died in the ED or were transferred were excluded from the analysis. CPT codes were used to identify patients who underwent DHC. Outcomes of interest included age, sex, total LOS, income, and mortality.

Results:
285,727 patients undergoing DHC for malignant unilateral MCA stroke were identified, with 52.81% being female. There was disproportionate representation of patients from the bottom two income quartiles (Q1: 28.02%, Q2: 26.73%), representing patients who make <$60,999 annually. The average age was 70.99yrs with 45.57% of patients 60-79yrs and 33.32% 80yrs and older, for a total of 213,907 patients 60yrs and older. Mortality rate for patients undergoing DHC was 10.59% overall. The mortality rate was nearly double in patients 80yrs and older compared to patients 18-39yrs (7.17% vs 13.98%) with a mortality rate of 10.17% for patients 60-79yrs. The average LOS was 9.81 days. Adjusting for patients who died in the hospital, 25.1% of patients 80yrs+ and 33.9% of patients 18-39yrs had a longer than average LOS.

Conclusion:
Patients undergoing DHC for malignant unilateral MCA stroke were disproportionately elderly patients with poorer survival outcomes than younger adults. Patients 80yrs and older have a higher incidence of mortality than younger patients and are nearly twice as likely to die after DHC than adult patients 39yrs or younger. Average LOS decreased with increased age adjusted for patients who died in hospital. Future research should focus on factors affecting mortality rate in older adults undergoing DHC.