bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP392: Effects of
Ripk2
Genetic Deficiency on Long-term Ischemic Stroke Outcomes in Aged Mice
Authors: Howell John , Larochelle Jonathan , Yang Changjun , Gunraj Rachel , Liu Lei , Candelario-Jalil Eduardo
Published: January 2025

Receptor-interacting serine-threonine protein kinase 2 (Ripk2) is a key enzyme in inflammatory signaling. Ripk2 has been shown to act through pattern recognition receptors that respond to bacterial endotoxins and damage-associated molecular patterns, triggering inflammatory cascades including TAK1, NF-κB, and MAPK pathways. Recent work has implicated Ripk2 as a therapeutic target in several inflammatory disease states, such as inflammatory bowel disease and autoimmune diseases like lupus and multiple sclerosis. In our lab, we have shown that Ripk2 contributes to secondary injury following ischemic stroke due to neuroinflammation. Previous work in our lab has shown that both global knockout and microglia-specific knockout of
Ripk2
in young mice are protective following stroke, resulting in smaller infarct size and fewer neurological deficits. Additionally, pharmacologically inhibiting Ripk2 is neuroprotective and reduces infarction and deficits after stroke. However, the impact of
Ripk2
deficiency on stroke outcomes in aged mice is unknown. We utilized
Ripk2
knockout (
Ripk2
-/-
) mice and wildtype (WT) mice (19-20 months old) and subjected them to permanent middle cerebral artery occlusion (pMCAO). Behavior tests were conducted for 28 days following pMCAO for longitudinal assessment of
Ripk2
deficiency on sensorimotor and cognitive deficits. These included the open field test, weight grip test, vertical grid test, novel object recognition test, cylinder test, and Y-maze.
Ripk2
-/-
mice performed better than WT controls on the vertical grid test on days 1, 3, 8, 15, and 22 (
p
<0.05, two-way ANOVA with Šídák’s post-hoc).
Ripk2
-/-
mice also had higher scores on the weight grip test compared to WT controls on days 3, 8, 15, and 22 (
p
<0.05, two-way ANOVA with Šídák’s post-hoc). Mice were sacrificed on day 28 following pMCAO for infarct size measurement and histology. While there was a trend toward smaller infarcts in
Ripk2
-/-
mice compared to WT mice at 28 days after stroke (
p
=0.0978), we found no statistically significant differences between groups in open field test, novel object recognition, cylinder test, or Y-maze. Experiments are ongoing to assess effects of
Ripk2
deficiency on microgliosis and astrogliosis in the ipsilateral hemisphere in brain sections. Our results significantly contribute to our understanding of the role that Ripk2 plays in ischemic stroke pathology by incorporating aged animals and long-term analyses of anatomical and behavioral outcomes.
Abstract WP396: Exploring Novel Neurovascular-Immune Biomarkers in Large Vessel Occlusion Stroke-Induced Pial Collateral Remodeling
Authors: Tanchanco Ocampo Collin , Ju Jing , Miner Alexandra , Ladner Liliana , Theus Michelle , Patel Biraj
Published: January 2025

Pial collateral vessels are small arterial branches connecting the major cerebral arteries, which help reroute cerebral blood flow in the event of large vessel occlusion. Patients with good pial collateral function recover better than those with poor function; however, the underlying etiology for this difference remains unknown. Pre-clinical rodent studies have identified angiopoietins, their subvariants, and receptor Tie2 in regulating collateral function and vascular remodeling following ischemic stroke. Currently, there are no safe and effective therapies to support tissue stability, recovery, or target collateral vessels in ischemic stroke patients. This study seeks to expand the current understanding of pial collateral plasticity by correlating cerebrovascular biomarker levels of Soluble Tie2, Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2) to collateral function in human patients with acute ischemic stroke. This prospective pilot study included whole blood collection at 3 time points from stroke patients (n=15) undergoing a mechanical thrombectomy. Protein expression was quantified via enzyme-linked immunosorbent assays (ELISA) and compared to matched healthy control serum. Standard-of-care imaging was analyzed to grade participants’ collateral function, and medical charts were reviewed to monitor long-term clinical recovery status. Linear mixed-effect models were conducted to compare biomarker activity levels across the 3 time points. Subjects with higher collateral function are associated with decreased levels of Ang1 and, conversely, elevated concentrations of Ang2 and soluble Tie2. Our findings suggest that greater pial collateral function correlates with alterations in Tie2/angiopoietin signaling due to large vessel occlusion stroke in humans.
Abstract WP4: Imaging-based Intravenous Thrombolysis for Patients ≥85 Years with Unknown Onset Stroke: EOS Individual Patient Data Meta-Analysis
Authors: Kamogawa Naruhiko , Miwa Kaori , Toyoda Kazunori , Jensen Marit , Inoue Manabu , Yoshimura Sohei , Fukuda-Doi Mayumi , Ma Henry , Ringleb Peter , Wu Ona , Schwamm Lee , Warach Steven , Hacke Werner , Davis Stephen , Donnan Geoffrey , Gerloff Christian , Thomalla Gotz , Koga Masatoshi
Published: January 2025

Introduction:
Previous studies have shown the efficacy and safety of time-based intravenous thrombolysis (IVT) in elderly patients with ischemic stroke. However, there are safety concerns about bleeding associated with IVT due to their low body weight, renal dysfunction, and the concomitant use of antithrombotic drugs. Robust evidence on the effect of IVT, particularly in elderly patients with unknown onset stroke, is limited. This study aimed to evaluate the efficacy and safety of imaging-based IVT in this population.

Methods:
Patients with an unknown onset stroke were evaluated using an individual patient-level database of randomized controlled trials comparing IVT with placebo or standard treatment from the Evaluation of unknown Onset Stroke thrombolysis trials (EOS) collaboration. The primary outcome was favorable outcome, defined as a mRS score of 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22–36 hours and 90-day mortality. The effect of IVT was evaluated in each of patients aged ≥85 and <85 years using a mixed-effect logistic regression analysis.

Results:
Among the 843 patients in the EOS dataset, 56 were aged 85 years or older (6.7%), and 787 were under 85 years (93.3%). The elderly group had a higher prevalence of atrial fibrillation (42.9% vs. 17.2%), hypertension (78.6% vs. 58.7%), and premorbid anticoagulation (13.6% vs. 3.1%). The baseline NIHSS score was also higher (median, 12 vs. 7) (all p<0.05). Overall, there was no significant interaction between age (≥85 or <85 years) and treatment on efficacy or safety outcomes (P interaction for the primary outcome 0.689). In the elderly group, favorable outcomes were observed in 33.3% of the IVT group and 19.2% of the control group, with an adjusted odds ratio (aOR) of 3.06 (95% CI 0.68-13.8). Mortality at 90 days was not significantly different between the IVT and control groups (20.0% vs. 19.2%, aOR 1.32 [0.30-5.79]), and there was only one case of sICH in the IVT group. In patients under 85 years, favorable outcomes were observed in 48.5% of the IVT group compared to 40.5% in controls (aOR 1.50, 95% CI 1.09-2.06). The IVT group had higher mortality (5.8% vs. 2.3%, aOR 2.56, [1.16-5.67]) and more frequent sICH (2.7% vs. 0.5%, aOR 5.35, [1.18-24.3]).

Conclusion:
Imaging-based IVT with alteplase may improve outcomes in elderly patients with unknown onset stroke without significantly increasing the risk of death or sICH.
Abstract WP40: Common and Distinct Circulating MicroRNAs Across Four Neurovascular Disorders
Authors: Koskimaki Janne , Jhaveri Aditya , Srinath Abhinav , Vera Cruz Diana , Yerradoddi Geetha Priyanka , Bennett Carolyn , Bindal Akash , Lightle Rhonda , Hsu Juhyon , Stadnik Agnieszka , Hage Stephanie , Alcazar-Felix Roberto , Iqbal Javed , Romanos Sharbel , Almazroue Hanadi , Loeb Jeffrey , Faughnan Marie , Weinsheimer Shantel , Kim Helen , Girard Romuald , Awad Issam
Published: January 2025

Introduction:
Familial cerebral cavernous malformations (FCCM), Sturge-Weber Syndrome (SWS), and hereditary hemorrhagic telangiectasia with brain arteriovenous malformations (HHT) are neurovascular disorders driven by genetic mutations while cerebral microbleeds (CMBs) are primarily associated with the aging process. All are associated with different vascular dysmorphisms and/or propensity to bleed.

Hypothesis:
We hypothesized that common and distinct circulating microribonucleic acids (miRNAs), reflecting shared and different pathobiology, can serve as potential biomarkers and therapeutic targets.

Methods:
Plasma miRNAs from patients with FCCM (n=10), SWS (n=10), and HHT (n=10) compared to age and sex-propensity-matched healthy young (HY) subjects (n=10) were extracted and sequenced. Similarly, CMB patients (n=10) were age and sex propensity-matched with healthy old (HO) subjects (n=10). Differentially expressed (DE) miRNAs of each disorder were identified (p<0.05, FDR corrected, absolute fold change [|FC|]>1.5]). Ingenuity Pathway Analysis (IPA) was conducted to determine gene targets and pathways of DE miRNAs. DE genes based on the transcriptome of each disorder were identified and utilized to filter gene targets of circulating miRNAs.

Results:
Eleven DE miRNAs were identified in FCCM, 40 in SWS, 41 in HHT, and 26 in CMB (p<0.05, FDR-corrected, [|FC|]>1.5]). Further analyses showed that 18 miRNAs were commonly dysregulated in two of the studied neurovascular disorders. IPA identified 17 genes targeted by at least two DE miRNAs in each of the four cerebrovascular disorders. Functional enrichment of those shared gene targets showed that PTEN, CDKN1A, NCL2L1, and CCND2 were involved in the PI3K-Akt Signaling Pathway. Moreover, the ROBO SLIT Signaling Pathway was identified as an involved pathway across all four disorders.

Conclusion:
The common dysregulated miRNAs across the disorders underscore their potential as biomarkers and therapeutic targets, reflecting their mechanistic involvement in shared pathophysiological pathways. Furthermore, the commonly targeted genes and implicated pathways suggest shared functionality of the miRNAs. These findings pave the way for further exploration of these miRNAs, aiming at the clinical application for disease monitoring and therapeutic intervention.
Abstract WP42: Comparative Outcomes of Unilateral vs Bilateral Revascularization in Moyamoya Disease: A Multicenter Retrospective Study
Authors: Musmar Basel , Roy Joanna , Abdalrazeq Hammam , Kaul Anand , Atallah Elias , El Naamani Kareem , chen jared , Jabre Roland , Saad Hassan , Grossberg Jonathan , Dmytriw Adam , Patel Aman , Khorasanizadeh Mirhojjat , Ogilvy Christopher , Thomas Ajith , Monteiro Andre , Siddiqui Adnan , Cortez Gustavo , Hanel Ricardo , Porto Guilherme , Spiotta Alejandro , Piscopo Anthony J. , Hasan David , Ghorbani Mohammad , Weinberg Joshua , Nimjee Shahid , Bekelis Kimon , Salem Mohamed , Burkhardt Jan-Karl , Zetchi Akli , Matouk Charles , Howard Brian , Lai Pui Man Rosalind , Du Rose , Abbas Rawad , Sioutas Georgios , Amllay Abdelaziz , Munoz Alfredo , Herial Nabeel , Tjoumakaris Stavropoula , Gooch Michael , Rosenwasser Robert , Jabbour Pascal
Published: January 2025

Background and Objectives:
Moyamoya disease (MMD) is characterized by progressive steno-occlusion of the internal carotid arteries, leading to compensatory collateral vessel formation. The optimal surgical approach for MMD remains debated, with bilateral revascularization potentially offering more comprehensive protection but involving more extensive surgery compared to unilateral revascularization. This study aims to compare bilateral revascularization and unilateral revascularization short-term safety profile in the treatment of MMD.

Methods:
This multicenter retrospective study included patients with MMD who underwent surgical revascularization at 13 academic institutions. Patients were categorized into unilateral and bilateral revascularization groups. Data collected included demographics, clinical characteristics, and outcomes. Propensity score matching (PSM) was used to balance baseline characteristics. Statistical analyses were conducted using Stata (V.17.0; StataCorp).

Results:
A total of 497 patients were included, including 90 that had bilateral revascularization and 407 that had unilateral revascularization. Bilateral revascularization was associated with more perioperative asymptomatic strokes (10% vs. 2.4%; OR 4.41, 95% CI 1.73 to 11.19, p = 0.002) and higher rates of excellent functional outcomes (mRS 0-1) at discharge (92.2% vs. 79.1%; OR 3.12, 95% CI 1.39 to 7, p = 0.006). After PSM, 57 matched pairs were analyzed. There was a higher rate, though not statistically significant difference, of perioperative stroke in the bilateral revascularization group (15.7% vs. 8.7%; OR 1.95, 95% CI 0.61 to 6.22, p = 0.26). No significant differences were noted in mRS 0-1 and 0-2 scores at discharge, NIHSS at discharge, intraoperative complications, or length of hospital stay. The follow-up stroke rates were also not significantly different (OR 0.40, 95% CI 0.11 to 1.39, p = 0.15).

Conclusion:
This study found no significant differences between bilateral and unilateral revascularization in MMD. Patients who had bilateral revascularization had higher tendency of perioperative stroke, though not statistically significant. Further prospective studies are needed to validate these results.
Abstract WP44: Homocysteine mediates the impact of PFO shunt on vascular cognitive impairment
Authors: Deng Wenjun , McMullin David , Buonanno Ferdinando , Lo Eng , Ning MingMing
Published: January 2025

Background:
Patent foramen ovale (PFO) is an independent risk factor for neurovascular injury such as stroke. We previously found that large PFO shunt is associated with increased long-term risk of vascular dementia. However, the mechanism underlying this association remains poorly understood. Our previous research revealed that PFO shunt enables the accumulation of homocysteine in circulation (Deng, Neurology 2021). It is thus possible that homocysteine may mediate the effect of PFO shunt on cognitive decline. This study aims to explore the relationship among PFO shunt, total homocysteine (tHcy) levels and the risk of vascular cognitive impairment and dementia (VCID).

Method:
A total of 1282 PFO patients were prospectively recruited and followed for over 11 years post their PFO closure in accordance with IRB protocol. All the patients were cognitively normal at the time of PFO diagnosis. Residual shunt post PFO closure was assessed using transthoracic echocardiogram (TTE) with saline contrast. Cognitive function was evaluated using Montreal Cognitive Assessment (MoCA). tHcy levels in peripheral venous blood was measured using mass spectrometry.

Result
Among the patients, 67 (5.2%) developed VCID as measured by MoCA < 26 and NINDS AIREN criteria. The risk of VCID was significantly high in patients with residual shunt, particularly those with large shunt size (no shunt: 5.0%; small shunt: 6.4%; large shunt: 11.5%), suggesting a dose effect of PFO shunt (OR: 1.53; 95% CI: 1.09 ~ 2.16; p = 0.014) (Figure 1A, Table 1). Moreover, residual PFO shunt also contributed to tHcy elevation in circulation (β: 0.44; 95% CI: 0.19 ~ 0.69; p < 0.001) (Figure 1B, Table 1), and high tHcy levels were linked to increased risk of VCID (OR: 1.87; 95% CI: 1.14 ~ 3.07; p = 0.013) (Figure 1C, Table 1). Further mediation analyses revealed a significant indirect effect of PFO shunt on VCID through tHcy (OR: 1.29; 95% CI: 1.01 ~ 1.66; p = 0.047) (Figure 1D, Table 1). tHcy mediated 40% (95% CI: 6% ~ 74%; p = 0.021) of the total association between PFO shunt and VCID risk (Figure 1D, Table 1). These findings remained robust after adjusting for other VCID risk factors, such as age, diabetes, hyperlipidemia and hypertension (Table 1).

Conclusion:
Our study suggested that that PFO shunt may contribute to the development of VCID by promoting circulatory tHcy elevation. Further mechanistic investigation of neurovascular injury and cognitive decline associated with PFO shunt is ongoing.
Abstract WP45: MRI-Visible Perivascular Spaces and Cognitive Performance: A Cross-Sectional Analysis from The Framingham Heart Study
Authors: Sisto Joseph , Rowsthorn Ella , Pinheiro Adlin , Araujo Contreras Robert , DeCarli Charles , Seshadri Sudha , Werry Amy , Romero Gabriela , Demissie Serkalem , Pase Matthew , Romero Jose
Published: January 2025

Introduction:
Perivascular Spaces (PVS) visible on brain MRI are fluid-filled compartments surrounding cerebral blood vessels. They are key indicators of cerebral small vessel disease (CSVD) and are associated with mild cognitive impairment (MCI) and dementia. This study aims to measure the effect of PVS location and severity on cognitive performance in adults from a community-based population.

Methods:
Framingham Heart Study participants from all cohorts with available MRI scans and neuropsychological (NP) test data within one year of each other were included in a cross-sectional analysis. PVS burden in the basal ganglia (BG) and centrum semiovale (CSO) was categorized into grades I-IV based on PVS counts. PVS burden was further dichotomized into high burden (Grades III&IV) vs low (Grades I&II). NP tests included were the Boston Naming Test (BNT30), Hooper Visual Organization Test (HVOT), Visual Reproduction-Delayed (VRD), Logical Memory-Delayed (LMD), and Trials B (TRB). Multiple linear regression models tested associations between PVS burden and each NP test, adjusting for age, sex, smoking, diabetes, hypertension, and education.

Results:
Among 3777 participants (mean age 60.6 ± 14.5, 46.4% male, 49% college educated, 17.5% CSO high burden, 9.8% BG high burden), we observed a general trend toward an inverse relationship between PVS burden and cognitive performance, although this trend was not significant in every model. Subjects with either high CSO or BG burden had slower completion time on TRB (β estimate 0.135, 95% Confidence Interval (CI): [0.036, 0.234], p-value: 0.008, and β: 0.346, 95% CI: [0.218, 0.475], p: <.0001, respectively). High CSO burden was also associated with lower test scores in VRD (β: -0.289, 95% CI: [-0.543, -0.034], p: 0.026), LMD (β: -0.342, 95% CI: [-0.681, -0.002], p: 0.049), and HVOT (β: -0.337, 95% CI: [-0.597, -0.077], p: 0.011).

Conclusion:
PVS high burden, notably CSO high burden, is associated with poorer cognitive performance in several cognitive domains. These findings suggest a role for MRI-visible PVS as an early biomarker for the identification of those at risk of MCI or dementia. Furthermore, PVS topography may be an important factor in understanding and predicting cognitive impairment. Further research tracking cognition across several exam periods is warranted, as well as possible effect modifications by genetic and environmental factors.
Abstract WP46: Racial and regional disparities on the prevalence and risk factors for cerebral microbleeds in the REason for Geographic and Racial Difference in Stroke (REGARDS) study
Authors: Ekenze Oluchi , Sawyer Russell P. , Niu Liang , Bennett Aleena , Cushman Mary , Lioutas Vasileios , Aparicio Hugo , Seshadri Sudha , Howard Virginia , Howard George , Romero Jose , Hyacinth Hyacinth I.
Published: January 2025

Introduction:
Cerebral microbleeds (CMB) are subclinical markers of cerebral small vessel disease (CSVD) denoting increased risk of stroke, cognitive impairment and dementia. The influence of race and region of residence on the prevalence, burden and brain location of CMB is understudied.

Aim:
Determine the impact of geographic and racial differences in prevalence and burden of CMB among participants in the REGARDS cohort study.

Methods:
Among the 30,239 participants followed since 2003-7 in the REGARDS study, CMB ratings was performed on MRI from those with stroke or TIA. CMBs were classified by brain topography as any CMB, non-lobar, and lobar CMB, and CMB counts were recorded. Multivariable logistic regression was used to assess the associations of race and region of residence (stroke belt vs. non-stroke belt) with CMB. We used negative binomial regression to relate race and region of residence with CMB count. Models were adjusted for age, sex and vascular risk factors such as hypertension, diabetes, smoking, total cholesterol.

Results:
Among participants with stroke or TIA, 808 had the correct sequence and thus CMB ratings. CMB was more prevalent in Black participants in both the stroke belt and non-stroke belt. Black participants with CMB were younger, and had higher proportion of hypertension compared to White participants with CMB. Black participants had higher odds of any CMB (OR 1.72; 95% CI 1.22, 2.43), non-lobar CMB (OR 1.59; 95 %1.02, 2.47), and lobar CMB (OR 1.66; 95% CI 1.13, 2.42) compared to White participants. Participants from the stroke belt had lower odds of any (OR 0.51; 0.37, 0.72), non-lobar (OR 0.53; 95% CI 0.34, 0.82) and lobar (OR 0.58; 0.40, 0.84) CMBs, as well as a lower odd of having zero CMB counts (RR 0.66, 95% CI 0.43 – 0.99) compared to non-stroke belt resident. Black persons residing in the stroke belt (RR 1.85, 95% CI 0.91 – 3.79) and non-stroke belt (RR 1.27, 95% CI 0.75 – 2.12) showed a trend towards having greater number of CMBs compared to White participants in both regions.

Conclusion:
Evidence of CSVD was more prevalent in general among Black participants. Additionally, Black participants with CMB were younger and more likely to have hypertension. Intervention to reduce brain health disparity will need to target hypertension as a risk factor.
Abstract WP53: Genetics of Cerebral White Matter Hyperintensities in Diverse Hispanic/Latino Adults
Authors: Fornage Myriam , Sofer Tamar , Isasi Carmen , Lipton Richard , Stickel Ariana , Tarraf Wassim , Gonzalez Hector , DeCarli Charles
Published: January 2025

Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging are part of the spectrum of brain vascular injury accompanying aging and are associated with an increased risk of stroke and dementia. WMH burden is greater among Hispanic than non-Hispanics white (NHW) adults. WMH is highly heritable and genome-wide association studies (GWAS) in older community-dwelling NHW and African American (AA) individuals have identified several genetic loci. However, the genetic architecture of WMH in Hispanic/Latino adults remains largely unknown.

We conducted GWAS and admixture mapping analyses of WMH volume in a sample of 2159 diverse Hispanic/Latino adults (mean age: 62.4 years; 66% women).

The proportion of variance in WMH volume attributable to common and low frequency variants in our sample was 28.9%, similar to a previous estimate in NHW individuals (29%). No association reached genome-wide significance. The strongest association was for rs60690281 (P=9.3x10
-8
). Accounting for population differences in linkage disequilibrium, we found evidence of transferability of 14 of the 27 known WMH loci. Interestingly, while there was no association of the chr10p14 locus, previously identified in AA, in our total sample, there was a suggestive association (P=0.08) in the Caribbean subgroup. Due to power limitations, we could not exclude transferability of the remaining loci. Multi-ancestry meta-analysis combining our GWAS results with those from GWAS of WMH in NHW and AA populations identified an additional locus on chr12q22 (P=1.8x10
-8
) tagged by rs10859915, an expression QTL of
AMDHD1
. Admixture mapping identified a novel locus on chr14q13.2, where counts of European ancestry at that locus were significantly associated with WMH volume (P=4.9x10
-7
). This locus spans an 800 kb region containing
RALGAPA1,
with known impact on neuronal function and brain development; and
INSM2,
encoding a transcriptional repressor influencing glucose metabolism.

Our study suggests that WMH loci previously identified in NHW and AA individuals are relevant to Hispanic/Latino adults. It demonstrates the power of the diverse Hispanic/Latino population to discover novel WMH loci and haplotypes, adding to our understanding of WMH genetic architecture.
Abstract WP58: Retinal Optical Coherence Tomography Abnormalities Associated with CADASIL: A Case-Control Study from the UK Biobank
Authors: Vallamchetla Sai Krishna , badr amro , Abdelkader Omar , Shourav Md Manjurul Islam , Li Xin , Wang Yalin , Meschia James , Dumitrascu Oana , Lin Michelle
Published: January 2025

Introduction:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, yet there is currently no biomarker for early detection. This study aims to identify retinal biomarkers of NOTCH3 carriers using optical coherence tomography (OCT) from the UK Biobank.

Methods:
We conducted a cross-sectional, matched case-control study of individuals with or without CADASIL from the UK Biobank between 2006 and 2010. All participants had retinal OCT scan and cognitive assessment. Cases were identified based on pathogenic NOTCH3 mutations and 1:1 matched with healthy controls based on age, sex, hypertension, diabetes mellitus, and smoking status. Baseline characteristics and cognitive test scores were compared using chi-square or Mann-Whitney-U test appropriately. Macular thickness (central, inner, and outer subfields) (Figure) and retinal nerve fiber layer (RNFL) thickness were compared using Wilcoxon signed-rank test.

Results:
Our analysis included 134 participants (67 CADASIL cases, 67 controls) with a mean age of 54±8 years. There were no differences in visual acuity between the two groups. CADASIL performed worse in prospective memory (0.043), verbal and numerical reasoning (p=0.178), visual memory (p=0.227), and processing speed (p=0.101) than matched controls. Participants with CADASIL had significantly thinner macular inner subfield at the superior (p=0.006), temporal (p=0.008), and nasal (p=0.034) quadrants, and significantly thinner RNFL (p=0.008) compared to controls (Table).

Conclusion:
Individuals with CADASIL have reduced thickness in the inner macular subfield and RFNL relative to matched controls. These retinal group differences were not associated with differences in visual acuity and may reflect early pericyte dysfunction and microvascular ischemia. Longitudinal studies are needed to assess the temporal relationship between these retinal changes and disease progression.
Abstract WP6: Associations between computed tomography biomarkers of cerebral small vessel disease and early outcomes after intravenous thrombolysis for acute ischemic stroke
Authors: Fang Shuangfang , Lei Hanhan , Wu Xiaomin , Lin Huiying , Huang Huapin , Liu Nan , Du Houwei
Published: January 2025

Background and Purpose:
Whether imaging markers of cerebral small vessel disease on computed tomography (CT-CSVD) relates to early clinical outcomes after intravenous thrombolysis for acute ischemic stroke remains not well understood. This multicenter retrospective study aims to investigate the association between baseline CT-CSVD score and early clinical outcomes in acute ischemic stroke patients who received intravenous thrombolysis.

Methods:
Individual CT-CSVD imaging markers and total score were assessed based on the following conditions: severe white matter lucencies (grade 2), two or more lacunes, and severe central or cortical atrophy (grade 2), with scores ranging from 0 to 3. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0-2 at discharge. The secondary outcome was early neurological deterioration, defined as a 2-point or greater decline on the NIHSS within the first 24h of admission. Multivariate logistic regression analyses were used to examine the associations between CT-CSVD scores and outcomes.

Results:
Of 920 eligible patients (median age 68, male 65.8%), 9.9% (91/920) experienced early neurological deterioration, and 62.1% (545/877) achieved functional independence at discharge. Patients with increasing CT-CSVD scores were older (p<0.001), more likely to have hypertension (p<0.001), diabetes (p<0.001), coronary artery disease (p=0.044), and a higher baseline systolic blood pressure (p=0.037). Multivariable logistic regression analyses showed increasing CT-CSVD score was associated with reducing odds of functional independence (categorical variable, vs. score 0, score 1: OR 0.68, 95%CI 0.46-1.02; score 2: OR 0.46, 95%CI 0.26-0.83; score 3: OR 0.16, 95%CI 0.03-0.76, overall p for trend = 0.007; per point increase, OR 0.65, 95%CI 0.51-0.83, p < 0.001) and increasing risk of early neurological deterioration (categorical variable, vs. score 0, score 1: OR 1.28, 95%CI 0.74-2.21; score 2: OR 1.69, 95%CI 0.81-3.52; score 3: OR 6.92, 95%CI 1.63-29.32; p for trend= 0.047; per point increase, OR 1.44, 95%CI 1.06-1.95, p = 0.019).

Conclusion:
This observational study showed that sum cerebral small vessel disease score on computed tomography was associated with a lower odds of functional independence and a higher risk of early neurological deterioration after intravenous thrombolysis for acute ischemic stroke.
Abstract WP60: Orosomucoid Expression in Cerebral Amyloid Angiopathy
Authors: UTSUNOMIYA TAKAYA , Nishigaki Akisato , Matsuyama Hirofumi , Ishikawa Hidehiro , Kajikawa Hiroyuki , Matsuura Keita , Niwa Atsushi , Maki Takakuni , Shindo Akihiro
Published: January 2025

Background:
Cerebral amyloid angiopathy (CAA), in which amyloid-β (Aβ) is deposited in cerebral and meningeal blood vessels, is associated with not only stroke but also cognitive dysfunction. CAA is classified as type 1 with capillary amyloid β (Aβ) or type 2 without capillary Aβ. Although it is known that CAA activates inflammatory responses, acute phase protein orosomucoid (α-1-acid glycoprotein) expression is still unclear.

Methods:
There were 26 autopsy brains, including 12 with CAA type1 and 10 with CAAtype2, 4 with other neurodegenerative diseases for control. We evaluated the extent of orosomucoid deposition in patients with CAA and control using pathological specimens, and also compared orosomucoid expression in type 1, type 2 CAA and control. Moreover, the relationships between orosomucoid and each clinical finding, such as history of hypertension, presence of lacunar infarct, cortical microinfarct, cortical superficial siderosis, and subcortical hemorrhage, were evaluated in CAA cases.

Results:
Vascular immunostaining for orosomucoid was identified more in CAA brains than in controls (p < 0.001). In the comparison between the three groups, immunohistochemistry higher expression of orosomucoid in the arteries/ arterioles of CAA type1 than control group. Although there was no relationships between orosomucoid and hypertension, lacunar infarct, cortical superficial siderosis, and subcortical hemorrhage, CAA with cortical microinfarct cases showed higher number of orosomucoid positive vessels than cortical microinfarct negative cases.

Conclusion:
Recently, we discovered that the levels of orosomucoid in the blood are elevated in patients with CAA. It was suggested that orosomucoid may be involved in the pathogenesis of CAA. Moreover, orosomucoid might be associated with type 1 CAA and cortical microinfact. As a limitation, the number of controls is small, so it is necessary to increase the number of cases.
Abstract WP61: Automated Retinal Vascular Fractal Analysis Can Screen Presymptomatic Alzheimer’s Disease
Authors: Nikolova Jennifer , Woodruff Bryan , Dumitrascu Oana
Published: January 2025

Background:
Retinal vasculopathy had been reported across the continuum of neurodegeneration. Retinal color fundus photography coupled with automated retinal vascular analysis offers potential to non-invazively screen for Alzheimer’s disease (AD) neurodegeneration. Amyloid positron emission tomography (PET) and apolipoprotein 4 (APOE4) carrier status are known biomarkers of AD risk. Herein, we examined the relationship between retinal vascular fractal dimensions in non-mydriatic color fundus photographs, amyloid-PET burden and APOE4 carrier status in a cohort of cognitively intact individuals.

Methods:
Our dataset included 91 macula-centered and 39 optic disc-centered images from 96 cognitively intact participants (29% male). 25 (26%) were amyloid-PET positive, defined as amyloid-PET standardized uptake value ratio centiloid cut-off > 20. AutoMorph software automatically determined retinal arteriolar and venular density, tortuosity and width, among other fractal dimensions. To test the effect of amyloid-PET status on the retinal vascular parameters, we used a generalized linear model compensated for age, sex and the interaction between APOE4 carrier and amyloid-PET status. We also compared amyloid-PET positive and negative subjects for vascular fractal dimensions correcting for age and gender. We adjusted for multiple comparisons using the False Discovery Rate correction and reported significant P values less than 0.05.

Results:
Compared to amyloid-PET negative, cognitively intact amyloid-PET positive cohort had greater mean age (71 vs 66 years, P=0.06), more males (60% vs 35%, P=0.02), more APOE4 carriers (P<0.001), similar vascular risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking, P>0.05 for all) and significantly lower macular vessel tortuosity density (P=0.019). The amyloid-PET positive status had a significant effect on the retinal artery distance tortuosity (corrected P=8.75E-04, β=13.9, 95% CI [7.75-19.99]) and artery squared curvature tortuosity (corrected P=8.91E-10, β=464, 95% CI [359.10-569.15]).

Conclusions:
Automatically determined retinal vascular fractal dimension on non-mydriatic color fundus photographs predicts amyloid-PET burden in cognitively intact individuals. Future longitudinal studies should asssess the utility of automated quantitative retinal vasculopathy analysis to screen for presymptomatic AD.
Abstract WP62: Post-stroke cognitive impairment and depression in a Brazilian nationally representative sample
Authors: M. R. Pinho Pedro J , Trombin Marques Marina , Sadala Reges Danyelle , Rocha Eva
Published: January 2025

Introduction:
Cerebrovascular diseases are the third leading cause of disability worldwide, which can occur due to the effects of Post-stroke Cognitive Impairment (PSCI) and Post-Stroke Depression (PSD). Higher morbidity and mortality are associated with both conditions following a stroke, but there is a lack of research on this topic in developing countries. We studied the prevalence of stroke and PSCI and PSD in a representative sample of the Brazilian population aged over 50 years, as well as the factors associated with both conditions.

Methods:
We performed a retrospective analysis of the ELSI-Brazil study, a nationally representative sample of adults aged 50 and over, including 9412 individuals. Individuals self-reported their sociodemographic characteristics, previous medical history, including prior stroke (transient ischemic attack, ischemic and hemorrhagic stroke), other chronic health conditions and disability in basic (b-ADL) and instrumental activities of daily living (i-ADL). Depression was defined as a score above 4 in the CESD-8 scale. Cognitive impairment was defined through a composite z-score including episodic memory, semantic memory, prospective memory, verbal fluency and orientation. After adjustments by age, sex and education, it was defined as a score below -1.0. Statistical analysis was performed using STATA/SE 17.0 software. Logistic regression was used to study the associated variables with PSD and PSCI.

Results:
From the total sample, 536 (5.3%) reported previous stroke. Of these, 58.6% had PSD and 31.8% had PSCI. Individuals who had a stroke were more likely to be older, male, of black race, have lower education, and more chronic health conditions. They also had higher disability in b-ADL and i-ADL, with higher depression and higher cognitive impairment. In the logistic regression, being a woman, having more chronic health conditions and higher disability in i-ADL were associated with PSD, while only being of black race was associated with PSCI.

Conclusion:
More than half of individuals with a previous stroke had depression and approximately a third had cognitive impairment. PSD was associated with being a woman, more chronic health conditions and higher disability in i-ADL. PSCI was associated with black race. Understanding the factors associated with PSD and PSCI is important to reduce stroke-related disability and promote better quality of life in individuals with previous stroke.
Abstract WP66: Astrocyte, Oligodendrocyte, and OPC Response in the Human Brain After Stroke: A Single-Cell RNA Sequencing Study
Authors: Zhao Chengcheng , Xiuhua Yao , Yilin Ma , Zhang Yue , Chen Tao , Ying Cai , chen jieli , WU JIALING
Published: January 2025

Introduction:
Ischemic stroke (IS) significantly alters brain cellular composition and gene expression, particularly in glial cells like astrocytes (ASTs), oligodendrocytes (OLs), and oligodendrocyte precursor cells (OPCs). While these cells' roles in neural repair are recognized, the precise molecular mechanisms remain unclear. This study aims to elucidate IS-induced transcriptomic changes in ASTs, OLs, and OPCs using single-cell RNA sequencing (scRNA-seq) of human brain tissues. We hypothesize that IS triggers distinct transcriptomic alterations in glial cells, crucial for post-stroke neural repair, which can be mapped to specific subclusters with unique functions.

Methods:
We performed scRNA-seq on five human brain tissue samples: three controls from craniocerebral trauma patients and two from IS patients. Tissues were collected from the frontotemporal regions within 48 hours of stroke onset. We analyzed 23,638 cells, identifying eight cell types. Differential gene expression, subcluster analysis, and trajectory analysis were focused on ASTs, OLs, and OPCs to explore the functional implications of the observed changes.

Results:
IS resulted in a marked increase in ASTs and OPCs, while OLs decreased in number. ASTs displayed significant transcriptional alterations, particularly in subclusters associated with synaptic signaling and axon development. Key upregulated genes included
NMNAT2 (
neuroprotection),
PPM1H (
involved in cellular stress response), and
NRP1
, (axonal guidance and the formation of synapses). OLs showed reduced presence post-IS, with subclusters enriched for synaptic regulation pathways. OPCs exhibited significant proliferation post-IS, with subclusters displaying divergent developmental trajectories, suggesting altered differentiation pathways due to stroke.Pseudotime analysis revealed distinct gene expression dynamics, with early-stage OPCs (Cluster 1) showing greater stemness compared to later-stage cells (Cluster 2).

Conclusion:
This study provides a detailed transcriptomic atlas of glial cell changes after IS, highlighting the critical roles of astrocytes, OLs, and OPCs in post-stroke brain repair. IS alters both cellular composition and gene expression, particularly in pathways related to synaptic transmission and neuronal development. These findings deepen our understanding of post-stroke recovery and suggest potential therapeutic targets for neural repair.
Abstract WP67: Acute ischemic stroke patients with high senescence gene expression have worse outcomes.
Authors: Contreras Real Maria Guadalupe , Falcione Sarina , Boghozian Roobina , Clarke Mike , Todoran Raluca , StPierre Alexis , Zhang Yiran , Joy Twinkle , Jickling Glen
Published: January 2025

Introduction:
Senescent cells accumulate with advancing age, and exposure to cellular stressors, such as oxidative and inflammatory molecules, which can be circulating in blood. Senescent endothelial cells have altered cellular functions that may influence stroke outcomes. Studying senescence might reveal improved strategies to improve vascular health and prevent stroke or better outcomes.

Hypothesis:
Acute ischemic stroke patients with enriched senescence gene set expression have worse 90-day stroke outcomes.

Methods:
In 225 patients with acute ischemic stroke, RNA was isolated from whole blood and transcriptome measured by microarray. Enrichment of senescence genes was assessed using the SenMayo gene set in Gene Set Enrichment Analysis (GSEA). The relationship between the SenMayo senescence score and patients’ 90-day modified Rankin scale (mRS) outcome was determined.

Results:
SenMayo senescence genes are enriched (p=0.05) in circulation of patients of acute ischemic stroke with bad outcome (90 day mRS>2) and not in patients with good outcomes (90 day mRS≤2) (fig.1). This suggests a role for senescent cells in the pathophysiology of stroke or as a contributing factor to the failure of the patient's full recovery.

Conclusion:
In acute ischemic stroke patients, increased senescence gene expression is associated with worse stroke outcome. Further evaluation is needed to determine whether targeting senescence could be a strategy to improve outcome in stroke.
Abstract WP7: To study the impact of presenting blood pressure on outcomes in acute ischemic stroke patients. Can permissive hypertension be re-defined with a range?
Authors: Srinivas Meghana , Marginean Horia , Stuchiner Tamela
Published: January 2025

Introduction:
Blood pressure is a simple physiologic parameter that is always measured, can be modulated, and may affect the outcome. In the hyperacute window, the therapeutic priorities are aimed at preserving penumbral tissue prior to reperfusion with the aim to optimize the chances of improved outcomes.

Blood pressure fluctuations early in the stroke can be a predictor of morbidity and mortality, and both high and low systolic blood pressures can negatively affect neurological outcome.

Objectives:
Investigate the effects of admission systolic blood pressure (aSBP) on outcomes in patients with acute ischemic stroke (AIS), with or without large vessel occlusion (LVO).

Methods:
This was a retrospective analysis of AIS patient data from a health system’s stroke registry for patients discharged between January 2018 and March 2024.

Adult (18+ yo) AIS patients with recorded aSBP to Thrombectomy Capable, Primary Stroke Plus or Comprehensive Stroke Center certified sites were included.

Discharge disposition (DD) was dichotomized as poor DD (Hospice, Expired) and favorable DD (Home, SNF/LTC, IRF) while the 90-day modified Rankin Scale (mRS) dichotomized as good outcome (0-2) and unfavorable outcome (3-6).

The relationship between the aSsBP , DD and 90-day mRS was analyzed using restricted cubic splines through multivariable mixed-effect models, adjusting for age, sex, race/ethnicity, NIHSS, treatment modalities, and medical history.

Results:
Data from 21,759 AIS patients were included, 72% aged ≥65 years, 49% female, 68% white, had median aSBP at admission 152 mmHg [interquartile range (IQR) 135, 172]; 3,016 (14%) had LVO.

Low aSBP is independently associated with reduced probability of good clinical outcomes (favorable DD and good 90-day mRS) overall and if LVO. (Table 1) The higher probability of good clinical outcome was found from approximately 150 mmHg, when it plateaus, to 180 mmHg.

Conclusions:
The term permissive hypertension is unique to each patient and needs to be optimized accordingly to achieve the best clinical outcome. This data will be beneficial in educating medical staff and making sure to optimize blood pressure especially during transfer to a certified stroke center.
Abstract WP70: Accelerating Stroke Care at an Academic Hospital: Evaluating the Impact of a Launchpad Initiative on Door-to-Needle Times One Year Later
Authors: Shoemaker Camella , Thompson Karen , Taylor Danielle , Morrison Amanda , Stallings Ashley , Shipley Sarah , Jones Tamicka , Rafferty Rachael , Reid Tonya , Shugrue Leah , COCCIA MICHAEL , Bakradze Ekaterina , SHAPSHAK DAG , Gropen Toby
Published: January 2025

Background:
Every minute is crucial in treating acute ischemic stroke (AIS), as the effectiveness of intravenous thrombolysis and endovascular therapy is highly time-dependent. AHA/ASA guidelines recommend door-to-needle (DTN) times of less than 60 minutes for at least 85% of AIS patients treated with IV thrombolytics, with further goals of achieving DTN times within 45 minutes for 75% of patients, and within 30 minutes for 50% of patients. However, less than a third of patients meet these time frames, prompting the implementation of a Launchpad protocol to hasten patient triage and intervention. This quality improvement initiative evaluates the Launchpad protocol's effectiveness at reducing DTN times in AIS treatment at an academic hospital, aiming to meet AHA/ASA guidelines and improve outcomes through a nurse-driven code stroke activation process. Fig.1. Updated Code Stroke Algorithm.

Methods:
A multidisciplinary team was assembled to address DTN delays by pinpointing treatment barriers. While the nurse-driven code stroke activation process has been a crucial development, it still requires enhancements to optimize the rapid identification and management of AIS patients. The Code Stroke Launchpad, located adjacent to the CT suite, was launched on 7.18.2023. Previously, AIS patients were triaged to the next open ED room resulting in AIS patients broadly distributed over a 60 room ED. The Launch Pad allowed the centralization of care to a defined area in close proximity to the CT scanner as well as helped expedite the intervention and evaluation of the multidisciplinary care team. The effectiveness of this new protocol is evaluated by comparing time differences before and after the Launchpad's implementation.

Results:
Post-Launchpad, door-to-needle times improved significantly: 84% of patients achieved the 60-minute target (up from 61%), 65% reached the 45-minute target (up from 39%), and 26% met the 30-minute target (up from 19%). Fig.2. Pre and Post DTN Averages

Conclusion:
The Launchpad implementation significantly reduced DTN times. Ongoing enhancements in nurse training, communication, and support are needed. Introducing Stroke Champions could further boost compliance and response times by ensuring regular updates and better coordination.