bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP389: Composite analysis of multi-category behavioral deficits for increasing the translational relevance of the mouse monofilament stroke model
Authors: Olivas Garcia Yamileck , Villa Jose , Chen Yingxin , Sajche Antonia , Sauer Kaley , Balakrishnan Rachana , Liu Chunli , Park Yujung , Osterli Emily , Hu Bingren
Published: January 2025

Background:
The variations in stroke volume are large and behavioral deficits are short-lived in rodent stroke models. These issues pose a challenge when using a rodent stroke model to test therapeutic interventions. The objective of this study is to explore composite analysis of multi-category behavioral outcomes for increasing the drug testing utility of the mouse middle cerebral artery occlusion (MCAO) model.

Methods:
Mice were subjected to 0 (sham), 20, 40, and 60 min MCAO, followed by 21 days of recovery. The rCBF was maintained at <10% of the normal level during MCAO. The naturally occurring post-MCAO hypothermia was corrected by a heating pad. Three outcomes (bodyweight for physical recovery; nesting for daily activity; and pole test for motor function) were documented at day-3, -7, -10, -14, and -21 post-MCAO. Dead mice were either excluded from analysis or imputed by assigning the worst score in the behavioral analysis. For the composite analysis, each sham mouse was assigned 33.3% per outcome, i.e., 100% per combination of the three outcome categories. Accordingly, relative to the sham value, the deficit percentage per outcome in each 20, 40, and 40 min MCAO mouse was calculated. The stroke volume was assessed at the 21-day endpoint. The relationships among stroke volume and behavioral outcomes were analyzed.

Results:
There is a positive relationship between stroke volume and behavioral deficits post-MCAO. Because of the limit of 10% rCBF during MCAO and post-MCAO hypothermia correction, the mortality rate reached to 80% in 60, 57% in 40, but 0% in 20 min MCAO group. When dead mice were excluded, the differences in mortality and behavioral deficits were statistically significant in all three category outcomes among 0 (sham), 20, 40, and 60 min MCAO groups before 7-day, but became insignificant after 7-day post-MCAO. When dead mice were imputed, the statistical significance in all three category deficits also become apparent after 7-day post-MCAO. Compared to the individual deficit analysis, the composite analysis of multi-category behavioral deficits further increases the statistical significance of behavioral outcomes post-MCAO.

Conclusion:
Stroke volume has a positive correlation only with imputed behavioral deficits post-MCAO. Compared to the individual analysis, the multi-category composite analysis can further increase the statistical significance of the behavioral outcomes post-MCAO or translational usefulness of the mouse model.
Abstract TP62: Education for Post-Acute Stroke Patients
Authors: Schmidt Joelle , Schweers Amy
Published: January 2025

Introduction:
Education for post-acute stroke patients is crucial for several reasons: recovery and rehabilitation, prevention of recurrence, empowerment, caregiver support, and health literacy. Education equips patents and their families with the knowledge/tools needed to manage the long-term effects of a stroke and overall well-being.

Background:
Mary Greeley Medical Center (MGMC) leadership identified a lack of compliance in patient education in the post-acute setting for stoke survivors. In 2019, only 60% of stoke patients in the MGMC Acute Rehabilitation Unit (ARU) received the necessary education to be successful at discharge.

Objective:
To use the best practices outlined by the American Heart Association’s (AHA) guidelines and increase our compliance to greater than 75% of all stroke patients in the ARU setting receiving education on; stroke warning signs, individualized risk factors, prevention, medication management, caregiver education, and after visit follow up.

Methods:
Our intervention involved implementing a standardized checklist in stroke patients’ rooms, clearly outlining essential educational components. This streamlined approach facilitated real-time assessment of education needs by both staff and patients. Upon admission, stroke patients received an informative packet containing AHA materials. We upgraded patient entertainment systems to include stroke-related educational videos. All educational documentation was integrated into the electronic medical record, enhancing accessibility for both staff and patients via MyChart. Caregivers can access this education via mobile devices. Nursing leaders engaged with patients during rounds to ensure effective utilization of these educational tools.

Results:
Over a five-year period, the implementation of improved patient education strategies led to a consistent increase in the proportion of patients receiving stroke education in the MGMC ARU. Starting from a baseline of 60% in 2019, the rate rose to 84% during 2020/2021, and further to 91% in 2022. The data for 2023 reflects a continuation of this positive trend. Leadership played a pivotal role by regularly assessing adherence to the education protocol and making continuous enhancements to the educational delivery process.

Conclusions:
The standardization of educational requirements and increasing the accessibility of a variety of learning platforms has increased staff compliance with providing the necessary education to stroke patients in the MGMC ARU.
Abstract TP86: Evaluating the Implementation of Brainomix 360 AI Stroke Software in a Robust Academic Hub-and-Spoke Telestroke Network
Authors: Smith Brett , Wolfe Jackson , Karam Alvina , Demaerschalk Bart , Hrdlicka Courtney , Nasr Deena , Chukwudelunzu Felix , Nord Charisse , Pahl Emily , Woodhead Zoe , Harston George , English Stephen
Published: January 2025

Background:
Artificial intelligence (AI) stroke imaging software is becoming mainstay in many hub-and-spoke hospitals. Brainomix 360 Stroke software is the market leader in Europe focused on leveraging simple imaging (non-contrast computerized topography (NCCT) and CT angiography (CTA)) and has recently been FDA-cleared for use in the USA. We evaluated the implementation of Brainomix 360 AI Stroke software in the 17 spoke, multi-state Mayo Clinic Health System (MCHS) telestroke network.

Methods:
This prospective study compared decision and treatment times before and after Brainomix AI implementation, as well as clinician feedback and simulated decision making to better understand any changes seen. Patients were included if they underwent telestroke evaluation at an MCHS emergency department within 90 days of implementation (2/9/2024-8/8/2024), and excluded if they were already admitted to the hospital or if video evaluation was not performed. Data collection included demographics, clinical decisions and treatment times. Qualitative surveys were conducted at baseline and evaluation end, as well as simulated decision making in 20 de-identified cases randomized to with/without AI through an online portal.

Results:
A total of 907 patients were included (444 pre- and 463 post-implementation, 287 (32%) with ischemic stroke final diagnosis). Median NIHSS was 2. IVT was recommended in 20.3% (27/148 ischemic stroke patients) pre- and 25.9% (36/139) post-implementation. EVT was recommended in 16.2% (24/148) pre and 14.4% (20/139) post. AI use was associated with trends of faster telestroke activation to IVT decision (36 vs 32 mins, p=0.6), IVT administration (47 vs 40 minutes, p=0.6), and EVT decision (36 vs 33 minutes, p=0.5). In the simulation, imaging interpretation was significantly faster when randomized to AI use (3.4 vs 2.1 mins, p<0.001) and associated with improved physician confidence (62 vs 88%, p=0.004). Qualitative feedback from 14/24 neurologists showed the greatest perceived value was improved confidence of treatment decisions (43%) and faster triaging (36%). Most value was gained from e-ASPECTS (NCCT) and LVO modules.

Conclusion:
This service evaluation highlighted the opportunity to improve efficiency of decision making even in the setting of a well-developed telestroke system. The impact was underpinned by the improved speed and confidence of imaging interpretation reflected in an offline simulation and qualitative feedback.
Abstract WMP1: Optimizing the ADC threshold for ischemic core delineation
Authors: Cohen Clara , Benzakoun Joseph , debacker clement , le berre alice , ben Hassen wagih , oppenheim catherine , Baron Jean Claude
Published: January 2025

Purpose:
In acute ischemic stroke, the typically employed 620×10
-6
mm
2
/s ADC threshold to automatically delineate the core on diffusion-weighted imaging (DWI) was established by overlaying the manually defined core onto the baseline ADC (ADC
0
) in recanalized patients following intravenous thrombolysis. However, recanalization was assessed 3-6hrs after treatment, which may entail substantial core growth, and follow-up imaging was at 90 days, implying infarct underestimation due to atrophy. Other studies typically used day 2-5 follow-up MRI (FU-MRI) but did not correct for vasogenic edema, implying infarct overestimation. We re-evaluated the ADC core threshold in patients with early recanalization following EVT, and applied edema correction on 24h post-EVT MRI.

Methods:
From our center’s EVT registry (2012-2021), all consecutive mothership patients with mTICI2c-3 recanalization within 90min after baseline MRI (MRI
0
) and who underwent FU-MRI at 24h post-EVT were included. Basilar occlusions and small DWI lesion (<3mL) were excluded. Edema correction was performed by applying non-linear coregistration of FU-MRI onto MRI
0
using the ANTs library. The baseline ischemic lesion was manually delineated on initial DWI (DWI
0
), and the final infarct ROI (Infarct
24h
) was manually delineated on non-corrected and edema-corrected FU-DWI. The intersection between DWI
0
and Infarct
24h
(the manual core) was then overlayed onto the ADC
0
, after exclusion of CSF and spurious ADC voxels. A ROC analysis then compared all ‘core’ voxels to ‘non-core’ voxels across patients, and the Youden Index was computed to determine the optimal ADC (OptADC) core threshold.

Results:
Across 56 eligible patients (median age: 73yrs; female 52%; median [IQR] NIHSS: 12 [8-19]), the mean ADC within the manual core was 609.8 (± 66.8)×10
-6
mm
2
/s and the OptADC was 584×10
-6
mm
2
/s without edema correction. The corresponding values with edema correction were 598.7 (± 69.1)×10
-6
mm
2
/s and 636×10
-6
mm
2
/s, respectively (both p<0.001 vs. non-corrected data).

Conclusion:
We report here the first ADC core threshold values derived from EVT-induced ultra-early complete recanalization using 24h follow-up MRI, with and without edema correction. Our strict selection criteria likely partly explain the substantially lower uncorrected ADC threshold found as compared to the classic 620×10
-6
mm
2
/s threshold. We also document the effect of edema correction on ADC threshold calculation when an early follow-up MRI is used.
Abstract WMP100: Multicenter Validation Study of Robot-Assisted Transcranial Doppler (raTCD) for Enhanced Right-to-Left Shunt Detection Compared to Transthoracic and Transesophageal Echocardiography
Authors: Walker Gregory , Yadlapati Ajay , Chang Ira , Schnapp william , Shah Ruchir , Devlin Christian , Khan Razi , Medvedev George , Naidoo Vishaya , Hernandez Sean , Pirahanchi Yasaman , Devlin Thomas
Published: January 2025

Background:
Cryptogenic strokes account for approximately 30-40% of all stroke cases, underscoring the critical need for effective identification of right-to-left shunt (RLS) and PFO. The recently published BUBL Study (NCT04604015), a multicenter, prospective trial, demonstrated a 3-fold increase in the detection of RLS/PFO using raTCD compared TTE. Wechsler recognized the study's important findings in an accompanying editorial, while also highlighting the need for further validation through additional studies. This study aims to provide robust real-world data to further substantiate the findings of the BUBL Study.

Methods:
This study involved a multicenter retrospective analysis of prospectively collected real-world clinical data across 5 centers in the US and Canada. The inclusion criterion was any patient who underwent raTCD for RLS detection as part of their stroke evaluation. A standardized TCD, TTE, and TEE bubble study protocol was consistently applied. Key outcomes include overall and large (Spencer Grade ≥3) RLS detection rates for raTCD, detection rates comparison between matched raTCD, TTE, and TEE.

Results:
A total of 1,372 patients underwent raTCD, with 455 and 114 had matched TTE and TEE respectively. The overall cohort had a mean age of 55.5 ± 13.3 yrs, with 44% female. Using raTCD, RLS was detected in 54% (735/1,372) and large RLS in 28% (383/1,372) of the overall population. When compared with TTE (n=455), raTCD identified 1.7 times more cases of RLS/PFO (56.7% vs. 33.2%, p<0.001 – Table 1). For all and large RLS detected by raTCD, 27.4% (125/455) and 12.3% (56/455), respectively were negative on TTE. Comparing TEE and raTCD, 14.9% (17/114) were negative on TEE but positive on raTCD compared to 5.3% (6/114) which were positive on TEE and negative on raTCD. Overall, using TEE as the “gold standard” raTCD reported a SEN of 92.1%. For the overall population (n=1,372) TTE and TEE status was unknown for 917 patients and will subsequently be investigated.

Conclusions:
This study represents the largest real-world study to date, validating raTCD against traditional diagnostic modalities. The study showed that raTCD detected 1.7 times the number of positive RLS/PFO compared to TTE, revealing the limitations of TTE as a screening modality for PFO in cryptogenic stroke. These results build upon the prospective multicenter BUBL Study reinforcing the imperative to incorporate raTCD into a new diagnostic algorithm for cryptogenic stroke workup.
Abstract WMP106: Stroke Risk and Urinary Albumin-to-Creatinine Ratio: A Post-Hoc Analysis of the ACCORD Trial
Authors: Kim Yvonne , Krothapalli Neeharika , Littig Lauren , de Havenon Adam
Published: January 2025

Introduction:
An elevated urinary albumin-to-creatinine ratio (UACR), a marker of renal dysfunction, has been linked to an increased incidence of stroke. However, the interplay between UACR and demographic factors such as age, obesity, ethnicity, or education remains underexplored.

Methods:
We conducted a post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, including patients with available data. Time-to-event models were developed to examine the relation between UACR and stroke risk during up to 10 years of follow-up, adjusting for variables such as gender, age, education, and race. Because the exposure of UACR had a right skew, we transformed it into top tertile versus lowest/middle tertile.

Results:
We included 9,025 ACCORD participants in our analyses. Baseline demographics are seen in Table 1. Those with elevated UACR (top tertile) had a higher incidence of stroke (4.6% vs 3.4%, p<0.001 in KM analysis, Figure 1). After adjusting for covariates, the multivariable Cox model still showed significance (adjusted HR 1.33, 95% CI 1.07-1.66, p=0.011). We further examined interactions between UACR and covariates including age, obesity, white vs other races, and education. For age and education, the interaction terms were not significant (p=0.216 and p=0.122). However, the interaction term for obesity warranted a stratified analysis (p=0.08). After stratification, we found that the effect of UACR was not significant in obese patients (p=0.385), but remained significant in non-obese participants (n=3345, HR 1.68, 95% CI 1.19-2.38, p=0.003). The interaction term for race was highly significant (p=0.01) and after stratification by race, UACR was not a significant predictor in white participants but showed significance in non-white patients (n=3373, HR 1.94, 95% CI 1.33-2.84, p=0.001).

Conclusion:
Increased UACR is associated with a higher risk of stroke, with the effect being more pronounced in non-obese and non-white patients. Further studies are warranted to better understand the role of UACR in stroke incidence, particularly in the context of patient demographic factors.
Abstract WMP112: Elimination of Senescent Cells with Immune Checkpoint Inhibitor Prevents Intracranial Aneurysm Rupture
Authors: Maeda Takuma , Take Yushiro , Uchikawa Hiroki , Nisson Peyton , Cisneros Oscar , Ishiguro Taichi , Sato Hiroki , Ai Jinglu , Lawton Michael , Hashimoto Tomoki
Published: January 2025

Introduction:
Clinical studies have shown an association between aging and the risk of intracranial aneurysm rupture. Aging leads to various changes in cellular homeostasis, including the onset of cellular senescence. Senescent cells secrete senescence-associated secretory phenotypes that leads to chronic vascular inflammation and abnormal vascular remodeling. Our preliminary data showed the accumulation of senescent cells in both human and mouse intracranial aneurysms, suggesting their potential role in the pathophysiology of intracranial aneurysms. We also confirmed that genetic elimination of senescent cells prevented aneurysm rupture. The immune system plays a critical role in eliminating senescent cells. However, in the pathological state, senescent cells can interfere with innate and adaptive immune responses through mechanisms known as immune checkpoints. Senescent cells express programmed cell death ligand 1 (PD-L1), which can bind to the programmed cell death protein 1 (PD-1) on immune cells. PD-L1-expressing senescent cells then evade clearance by immune cells. We investigated the effect of an immune checkpoint inhibitor on the development of intracranial aneurysm rupture.

Methods:
We used 15-month-old male C57BL/6J mice (n = 29). We induced intracranial aneurysms by a combination of elastase injection and hypertension. After aneurysm induction, we started treatment with anti-PD-1 antibody as an immune checkpoint inhibitor or IgG2 as a vehicle. We compared the aneurysm formation and rupture rates, and the survival curve between the two groups. We also assessed the effects of anti-PD-1 antibody on the mRNA expression of p16 as a senescent cell marker in cerebral arteries.

Results:
The aneurysm rupture rate was significantly lower in the treatment group than in the vehicle group (54.5% vs. 100%,
P
<0.05, Fig. A and B). There was no statistical difference in the aneurysm formation rate between the two groups (78.6% vs. 71.4%,
P
>0.99, Fig. A). Mice treated with anti-PD-1 antibody had a better survival rate than the control group (
P
=0.053, Fig. C). Treatment with anti-PD-1 antibody significantly reduced the mRNA expression of p16 in cerebral arteries (
P
<0.05, Fig. D).

Conclusions:
Treatment with immune checkpoint inhibitor prevented intracranial aneurysm rupture. Our findings suggest that cellular senescence and immune checkpoint may serve as novel therapeutic targets for the prevention of aneurysm rupture.
Abstract WMP115: Towards a Comprehensive Computational Model of Ischemic Stroke: Integrating Detailed Microvasculature With Advanced Model of Brain Tissue Metabolism
Authors: Dehkharghani Seena , Brantner Douglas , Ventimiglia Thomas , Collins Christopher , Linninger Andreas
Published: January 2025

Intro:
Resources for studying stroke are limited to clinical trials with sparse access to physiological and biochemical details, and pre-clinical animal studies with limited relation to humans. A physiologically accurate in silico model would provide a new route for study of the response to an ischemic event. Here we combine a computational model of brain tissue metabolism modified to simulate effects of ischemia (1) with an experimentally-validated approach to model the distribution of nutrients to the extravascular space as provided by a specific cerebral microvasculature network (2,3) to produce simulations of ischemic stroke showing the spatial distribution of damaged and healthy tissue.

Methods:
Anatomically-accurate models of cortical microvasculature and resulting O2 concentration with consideration of oxygen consumption in tissue were developed and validated against experimental measures of pO2 (2,3, Figure 1). A numerical implementation of a 4-compartment cellular model of brain metabolism (4) was modified to simulate ischemic stroke (1), and further modified to consider effects of the local pO2 and Glucose (GLC) as provided by the vascular network by adjusting local rates of transfer of GLC and O2 into the neuronal compartment of the cell, as shown in Figure 2, bottom. Brain metabolism was simulated for cases with no ischemic event, and after CBF was reduced by 80%.

Results:
Figure 2 shows timecourse of GLC, ATP, and Sodium in different compartments of the model through time in regions experiencing mild and severe ischemia. Figure 3 shows intraneuronal sodium concentration before and 2 hours after onset of an ischemic event showing failure of sodium pumps during ischemia.

Conclusion:
Effects of ischemic stroke on cerebral metabolism at the cellular level with consideration of microvasculature and distribution of nutrients within the tissue can be modelled at the capillary and cellular level computationally. Future work will include linking astrocytes to local nutrient concentrations and expansion of the simulated region to include larger region of brain, so an ischemic core and penumbral region surrounded by unaffected tissue can be observed.

References

1. CM Collins et al. International Stroke Conference, February 7-9 2024, Phoenix

2. T Ventimiglia et al. Int J Numer Meth Biomed Engng. 2023;39:e3735

3. G Hartung et al. PLOS Computational Biology 2020;17(1): e1008584

4. M Cloutier et al. Journal of computational neuroscience. 2009 Dec 1;27(3):391
Abstract WMP118: Thrombin generation is associated with outcome in patients with stroke treated with thrombolysis
Authors: Falcione Sarina , Joy Twinkle , Munsterman Danielle , Sai Sushreeta , Boghozian Roobina , Jickling Glen
Published: January 2025

Background and Purpose:
Thrombolysis can improve outcome in patients with acute ischemic stroke. However, recanalization is not always complete with persisting cerebral vascular occlusion in >50% of patients despite treatment. Properties of the formed thrombus may influence thrombolysis efficiency and impede recanalization success. Here we examine whether differences thrombin generation are associated with unfavourable outcome in thrombolysis treated patients with acute ischemic stroke.

Methods:
Two cohorts of patients with acute ischemic stroke treated with thrombolysis were recruited (cohort 1 n=36 patients, cohort 2 n= 42). Thrombin generation was determined by thrombin generation assay and related to stroke outcome at 90-days determined by modified Rankin Scale (mRS). The relationship of thrombin concentration to clot lysis rate was examined
in vitro.
Inflammatory factors associated with increased thrombin generation were also identified.

Results:
An increase in peak thrombin was associated with unfavourable 90-day outcome in patients with acute ischemic stroke treated with thrombolysis. In cohort 1, patients with mRS£2 had a mean peak thrombin of 208.4nM compared to 255.5nM in those with mRS>2 (p=0.019). In cohort 2, patients with mRS£2 had a mean peak thrombin of 211.1nM compared to 251.6nM in those with mRS>2 (p=0.019).
In vitro
, an increase in thrombin concentration slowed the rate of clot lysis by tPA. In patients with stroke, an increase in peak thrombin was associated with increased plasma interleukin (IL)-6, interleukin-8 and a decrease in a2-macroglobulin.
In vitro
, IL-6 can was found to increase thrombin generation via monocyte tissue factor.

Conclusions:
Increased thrombin generation on admission is associated with unfavourable outcome at 90 days in thrombolysis treated stroke patients. Higher thrombin generation may influence thrombus properties, reducing effectiveness of thrombolysis, and impairing recanalization. Further understanding regarding the relationship of thrombin generation to thrombolysis is necessary to enhance recanalization and further improve outcomes in stroke.
Abstract WMP119: Oral Contraceptive Exposure Increases Cerebral Sphingolipid Metabolites And Exacerbates Post-Stroke Cognitive Decline In Female Rats
Authors: Sharma Sabrina , Raval Ami
Published: January 2025

Introduction:
About 65% of women in their reproductive years use contraception, with combined oral contraceptives (OC) being among the most popular. OC, which contain estrogen and progestin, are linked to a higher risk of stroke, particularly in the first year of use. This study aims to explore the mechanisms and effects of OC exposure on stroke outcomes.

Methods:
Adult female Sprague-Dawley rats (n= 6-8/group) were randomly assigned to receive either a placebo or OC by oral gavage for 12-14 estrous cycles. The animals were divided into two cohorts following treatment. In the first cohort, brain tissue was harvested to obtain an unbiased global metabolomic profile (Metabolon Inc.) This metabolomic analysis was supplemented with western blotting and enzyme activity measurements of key altered pathways. The second cohort underwent either transient middle cerebral artery occlusion (tMCAO; 90 min) or sham surgery and was observed for 21 days. During this post-tMCAO/sham period, cognition was assessed using the Morris water maze, followed by brain collection for histopathological and immunohistochemical analysis.

Results:
OC exposure significantly increased infarct volume and impaired cognition in rats compared to the placebo group. Metabolomic analysis revealed significant alterations in sphingolipid metabolism, particularly an increase in sphingosine 1-phosphate (S1P) levels (p<0.05) in OC-exposed brains. A crucial enzyme for generation of S1P is Sphingosine Kinase 2 (SphK2) in the brain. Western blot analysis confirmed significant increases in SphK2 protein levels upon OC exposure. Additionally, OC exposure led to a significant decrease in sphingosine 1-phosphate lyase protein levels, responsible for S1P degradation. We also observed a notable increase in S1P receptor 3 protein levels, which plays a key role in inflammation. Therefore, microglial activation was quantified in the brain following tMCAO.

Conclusion:
The data indicate that OC exposure worsens ischemic outcomes by altering S1P metabolism. Future studies are needed to better understand S1P's role in OC-induced ischemic outcomes, which could help identify potential therapeutic targets.
Abstract WMP16: Impaired Neurocognitive Domains Related To Quantitative Brain Functional Abnormalities In Patients With Unilateral Asymptomatic Middle Cerebral Artery Stenotic-occlusive Disease
Authors: Zou Yinxi , Liu Caiyan , Liu Linwen , Li Mingli , Xu Wei-hai
Published: January 2025

Background:
The patterns of neural functional changes induced by chronic hypoperfusion resulting from intracranial arterial stenosis and their relationship to cognitive performance are not yet fully understood, with unilateral asymptomatic middle cerebral artery stenotic-occlusive disease (MCAs/o) serving as an ideal model for investigation.

Methods:
We established a discovery-validation research pipeline to identify functional abnormalities in the hypoperfused regions of MCAs/o patients and quantify them into a machine learning-based data-driven biomarker, i.e. hypoperfusion-based functional abnormalities (HFA). Pseudocontinuous arterial spin labeling imaging was used to identify hypoperfused regions (HypoR) in the discovery cohort. Functional changes within HypoR, including regional homogeneity (ReHo) and functional connectivity, were analyzed and quantitatively integrated using a logistic regression machine learning model to calculate the HFA after feature extraction. The correlation between HFA and cognitive scores was then assessed, and the findings were validated in the independent cohort
(Figure 1).

Results:
The discovery cohort included 44 MCAs/o patients (LMCAs/o: n=22, age 56±11 years, 13 male; RMCAs/o: n=22, age 49±14 years, 16 male) and 35 matched normal controls (age 52±11 years, 15 male), in which MCAs/o patients showed poorer performance on bilateral hand-grooved pegboard tests (GPT) compared to controls (p<0.05). We identified 45 regions of interest (ROIs) in the stenotic hemisphere with significantly elevated arterial transit time, defining them as hypoperfused areas. We found that MCAs/o patients had increased ReHo(FDR-p<0.05) and reductions in HypoR~non-HypoR connections(FDR-p<0.05), coupled with increased HypoR~HypoR connections(FDR-p<0.05). HFA was then calculated based on functional features, which effectively identified early functional changes in MCAs/o patients(AUC=0.994) and correlated with bilateral GPT(p<0.001) (
Figure 2
). Validation in an independent cohort(20 MCAs/o, 16 controls) confirmed these findings(AUC=0.948; HFA~bilateral GPT p<0.01,
Figure 3
).

Conclusions:
Chronic hypoperfusion caused by unilateral MCAs/o can lead to a specific pattern of functional changes characterized by increased local neural activity. The quantified biomarker of this pattern can be used to monitor the decline in cognitive function. Our study provides a foundation for further research into the neural damage caused by chronic hypoperfusion.
Abstract WMP21: Ten Year Increases in White Matter Hyperintensity Volume Correlates with the Severity of Ongoing Blood Brain Barrier Permeability when Measured with Dynamic Susceptibility Contrast MRI
Authors: Sasannia Sarvin , Leigh Richard , Wang Shimeng , Matsyuk Mykola , Zhang Jinwei , Shin Hyeong-Geol , Prince Jerry , Becker Lewis , Yanek Lisa , Vaidya Dhananjay , van Zijl Peter , Knutsson Linda , Nyquist Paul
Published: January 2025

Introduction:
Blood-brain barrier (BBB) dysfunction is increasingly recognized as a key factor in the pathogenesis of cerebral small vessel disease (cSVD). Typical brain Magnetic Resonance Imaging (MRI) findings of cSVD include white matter hyperintensities (WMH). Based on their anatomical locations, WMH can be classified as Periventricular WMH (PVWMH), which are immediately adjacent to the ventricles, or deep WMH (DWMH), which are subcortical. This study aimed to investigate the relationship between BBB permeability as measured by Dynamic Susceptibility Contrast (DSC) MRI, and changes in total WMH, PVWMH, and DWMH volume over 10-13 years in asymptomatic individuals enriched for vascular risk factors.

Hypothesis:
Higher K2 measurements, which reflect leakage of contrast due to increased BBB permeability, derived from second MRI will corelate with increases in WMH, DWMH, and PVWMH volume that occurred over the previous decade.

Methods:
We included 100 volunteers from GeneSTAR, an ongoing family-based study of families enriched for vascular risk factors and cardiovascular disease, age = 63.3 ± 9.5 years, 60% females, 63% Hypertension, 22% African Americans. Two MRI’s were obtained 10-13 years apart using 3T scanners. At each visit total WMH, PVWMH and DWMH volumes were determined using automated software with consistent co-registration (Figure 1). K2 was measured for each individual by averaging the highest 100 voxels (hotspots) within the regions of interest in each individual lesion using a gadolinium-based DSC-MRI at the second visit (Figure 2). Linear regression models used to analyze the relationship between K2 and volume changes in total WMH, PVWMH, and DWMH, adjusting for age, systolic blood pressure, race, sex, and education.

Results:
Positive correlations between K2 at time point two and changes in volume were statistically significant for total WMH (R-squared = 0.497, p = 0.006), PVWMH (R-squared = 0.461, p = 0.0085), but did not reach significance for DWMH (R-squared = 0.394, p = 0.08) (Figure 3).

Conclusion:
The robust correlation between K2 and overall WMH volume change underscores the potential of K2 as a biomarker for monitoring ongoing disease activity for subclinical cerebrovascular changes in at-risk populations.
Abstract WMP36: Reliability of ICD-10 codes for Stroke in a Representative US Population
Authors: Gutierrez Quiceno Laura , Robinson David , Ferioli Simona , Wechsler Paul , Stanton Robert , Aziz Yasmin , Laporta Joseph , Menzies Lauren , Felipe De los Rios La Rosa , Stamm Brian , Haverbusch Mary , Walsh Kyle , Slavin Sabreena , Nobel Lisa , Wright Shea , Ding Lili , Kleindorfer Dawn , Woo Daniel , Kissela Brett
Published: January 2025

Introduction:
ICD-10 codes are often used for stroke research in administrative databases. Few studies have assessed their reliability in large, representative populations of the United States. We validated ICD-10 codes in a large population-based study of stroke in the Greater Cincinnati/Northern Kentucky (GCNK) region.

Methods:
We ascertained all acute strokes in the GCNK region during 2020 using validated methodology. All hospitalizations were screened using a comprehensive list of ICD codes in any diagnosis position (G45-46/H34/I60-69). Additional cases were captured through cold pursuit. Each case was adjudicated by a stroke-trained physician. Only acute ischemic stroke (AIS) and hemorrhagic strokes (HS, defined as intracerebral hemorrhage or subarachnoid hemorrhage) were included in this analysis. We examined how many AIS cases were identified using the standard codes used for administrative studies (G46/I63), assessing their sensitivity and positive predictive value (PPV) in the primary or secondary positions. A similar analysis was conducted using standard HS codes (I60/I61). Differences in the demographics of cases identified with standard codes in the primary position, standard codes in the secondary position, or through other methods were then evaluated with Chi-squared and Kruskal-Wallis tests.

Results:
We identified 3,522 AIS/HS events in 2020. For AIS (Table 1), we found that standard codes in the primary position had a sensitivity of 72.8% and a PPV of 89.1%. When the standard AIS codes were considered in any diagnosis position, sensitivity improved to 89.3%, but PPV decreased to 82.3%. For HS, standard codes in the primary position had a sensitivity of 80.0% and a PPV of 81.0%. When the standard HS codes were considered in any position, the sensitivity improved to 93.4% but the PPV decreased to 54.4%. When looking at baseline characteristics (Table 2), patients identified through a standard code in the primary position had a lower baseline mRS (overall P<0.01); nursing home residence was also more common in patients identified through a standard code in the secondary position (7.8%, overall P<0.01).

Conclusion:
For AIS, standard codes in the primary position showed only moderate sensitivity but reasonable PPV. For HS, standard codes in the primary position had moderate sensitivity and moderate PPV. Restricting analyses to patients with a standard code in the primary position likely selects against patients with more disability at baseline.
Abstract WMP37: Prevalence of LRP4 and AGRIN Antibodies in Stroke Patients with Post-Stroke Fatigue: An Observational study
Authors: NAMBIAR VIVEK , PT Karthika , kannoth Sudheeran , Mathai Annamma , Chandran Divyasree , V U Anaghakrishna
Published: January 2025

Introduction:
Post-stroke fatigue (PSF) is a common and debilitating consequence of cerebrovascular accidents, potentially stemming from central and peripheral mechanisms. Recent studies have linked myasthenia gravis-related antibodies to PSF, though data on their role remains limited. Current treatments for PSF are often ineffective, underscoring the need for more research into its underlying causes and management.

Objectives:
This study investigates the presence of myasthenia gravis-related antibodies in patients with PSF after motor recovery, focusing on low-density lipoprotein receptor-related protein 4 (LRP4) and AGRIN antibodies. We aim to evaluate their clinical response to targeted therapies, excluding anti-AChR and anti-MuSK antibodies.

Methods:
We conducted a cross-sectional study involving patients with PSF who had undergone myasthenia antibody testing. The study cohort included individuals with fatigue following good motor recovery, who tested positive for LRP4 and AGRIN antibodies. Clinical, demographic, and imaging data were analyzed, with clinical response assessed using the Modified Rankin Scale (mRS) at follow-up.

Results:
Among 935 patients at the stroke unit over two years, 50 were tested for myasthenia antibodies due to PSF. Of these, 17 (34%) were positive for either anti-AGRIN (70.58%) or anti-LRP4 (64.71%) antibodies. Fatigue was reported by 82.35% of the antibody-positive patients. This group consisted of 35.29% females with a mean age of 66.7 years. Most had a history of ischemic stroke (88.23%), with 11.76% having experienced hemorrhagic stroke.

All 17 patients received cholinergic medications, showing significant improvement in mRS scores. The Wilcoxon signed-rank test revealed a p-value of <0.0001, indicating a statistically significant enhancement in mRS scores.

Conclusions:
Our study suggests that PSF may be linked to myasthenia gravis-related antibodies, specifically anti-LRP4 and anti-AGRIN. This finding is significant for treating PSF and improving fatigue symptoms, particularly in cases refractory to standard treatments.
Abstract WMP39: First External Validation of the Predictive Swallow Score
Authors: Ikramuddin Salman , Weiss Martin , Datta Abhigyan , Yang Sophia , Ryan Dylan , Park Christine , kumar sandeep , Xenopoulos-Oddsson Annette , Cui Erjia , McCullough-Hicks Margy , Feng Wayne
Published: January 2025

Post-stroke dysphagia (PSD) is a common complication following stroke. Predicting the recovery from PSD remains a major challenge. The Predictive Swallow Score (PRESS) model, derived and validated in Switzerland, sought to predict recovery from PSD after an acute ischemic stroke (AIS). We sought to perform the first external validation of the PRESS model.

A two-center retrospective cohort study of 149 dysphagic patients with functional oral intake scale (FOIS) ≤4 following AIS was conducted. Demographic data and clinical co-variates (age, NIHSS, ANY2 score, frontal opercular stroke, FOIS) were collected to predict the recovery from dysphagia at post-stroke day 7. The primary outcome was impaired swallow at day 7 (FOIS ≤ 4).

The mean age was 72.1 years (±16.0) and 79 (53%) were females. Median (Q1-Q3) NIHSS at presentation was 14 (7-20), ANY2 score 5 (3-6), FOIS at presentation 1 (1-4). 66 patients had frontal-opercular involvement of stroke. Median FOIS at 7-day follow-up from stroke was 4 (1-5), with 71 (44%) being classified as impaired. The Hosmer-Lemeshow test rejected the null hypothesis that the PRESS model was a good fit to the validation data (p=<0.0001, x
2
=55.735, df=5). Calibration curve analysis revealed that the PRESS model overpredicted the likelihood of persistent dysphagia. The C-statistic of the PRESS model on the validation cohort was 0.74 (95% CI: 0.65-0.81). In a secondary analysis, impaired subjects (FOIS ≤ 4) at day-7 had a higher median (Q1-Q3) admission NIHSS (15 [7.5-21] vs 12 [6-17], p=0.02), ANY2 score (6 [4-6] vs 4 [3-5], p<0.0001), PRESS score (8 [6-9] vs 5 [2-8], p<0.00001), and higher frequency of frontal opercular stroke location (64% vs 46%, p=0.03). However, age (p=0.17) and sex (p=0.07) were associated with persistent dysphagia at day 7.

This first external validation study of the PRESS model did not support its use as a tool to predict recovery from PSD, potentially owing to regional variation in the predictive power of certain co-variates such as stroke severity, stroke location, and age. The study is limited by its retrospective design. A larger prospective cohort study is needed to evaluate the PRESS model prior to clinical adoption.
Abstract WMP4: Intravenous Thrombolysis in Patients on Direct Oral Anticoagulants: Analysis of the Get With Guidelines Stroke Registry
Authors: Yaghi Shadi , Shu Liqi , Mistry Eva , Adeoye Opeolu , Schwamm Lee , Messe Steven , Elkind Mitchell , Ghannam Malik , de Havenon Adam , Furie Karen , Xian Ying , Streib Christopher , Wangqin Runqi , Henninger Nils , Saver Jeffrey , Smith Eric
Published: January 2025

Background and Purpose:
Intravenous thrombolysis for acute ischemic stroke (AIS) is a proven effective treatment. Whether thrombolysis in AIS patients with recent direct oral anticoagulant (DOAC) use is safe and efficacious is not well established. We aimed to compare outcomes of patients with AIS and recent DOAC use who received thrombolysis to those otherwise eligible but excluded from thrombolysis due to recent DOAC use.

Methods:
This study included patients entered into the Get with the Guidelines (GWTG) registry with a diagnosis of AIS who presented to an acute care facility within 4.5 hours from last known normal, used a DOAC within 7 days before hospital arrival, and either: 1) received intravenous thrombolysis, OR 2) were excluded from thrombolysis with coagulopathy being the only reason for exclusion. We used univariate and adjusted binary logistic regression models with clustering by site to compare the two groups’ functional status (ambulation on discharge and discharge disposition) and reported rates of safety outcomes in the thrombolysis group (symptomatic intracranial hemorrhage, extracranial hemorrhage, and death).

Results:
The study sample included 48,907 AIS patients using a DOAC; 4,702 received thrombolysis and 44,205 did not. The mean age was 75.1 years and 50.5% were men. In adjusted logistic regression models, patients with recent DOAC use receiving thrombolysis were more likely to ambulate independently at discharge (OR 1.35, 95% CI 1.21-1.50) and to be discharged home (OR 1.33 95% CI 1.22-1.46). The rate of symptomatic intracranial hemorrhage with intravenous thrombolysis in patients with recent DOAC use was 3.5% (95% CI 3.0%-4.1%).

Conclusions:
In this analysis of the GWTG registry, intravenous thrombolysis was associated with improved functional outcomes in patients with recent DOAC use and appeared safe. Given the limitations of our real-world registry analysis, these findings require validation by prospective trials.
Abstract WMP41: Evaluation of a Digital Cognitive Self-Assessment Method for Post-Stroke Cognitive Decline
Authors: Gupta Antara
Published: January 2025

Introduction:
Post-stroke cognitive decline (PSCD) is a common complication of strokes, and early assessment is crucial. However, outpatient cognitive assessment protocols are inconsistent, leading to missed diagnoses of PSCD. A potential solution is the XpressO application, introduced in 2023 by the creators of the Montreal Cognitive Assessment (MoCA). Because XpressO is self-paced, it can be completed by patients while waiting for an appointment and hence can assess cognition without impacting clinic workflow.

Hypothesis:
This study aims to investigate the feasibility of using the XpressO online self-administered cognitive assessment and compare its ability to detect PSCD with the MoCA short form (MoCA-sf) at our out-patient stroke clinic.

Methods:
Patients at the clinic with a history of ischemic or hemorrhagic strokes were included. We used <12 as the cutoff to determine low performance on the MOCA-sf. After their clinic visit, participants consented and completed a screening survey on stroke risk factors, followed by both the MoCA-sf and XpressO assessments. Completion times for both assessments were recorded, and results were analyzed using R Studio.

Results:
We enrolled 32 patients and 32 completed the assessment. The results of this study found a moderate correlation between Xpresso and MOCA-sf (ρ = 0.645, p = 6.70e-05). When stratified by cognitive function, no significant correlation was observed between XpressO and higher MoCA-sf (≥12) scores (ρ = 0.128, p = 0.691). The average time to complete the assessment was 6.63 minutes for MOCA –sf and 6.28 minutes for Xpresso. This difference was not significant. However, when stratified by cognitive function, there was a significant difference in completion time between XpressO (4.43 minutes) and MoCA-sf (5.83 minutes).

Conclusion:
The results suggest that XpressO is better at detecting severe cognitive decline but is less sensitive to milder impairments. Time to complete each test differed significantly only in patients with higher cognitive function, with XpressO being faster than MoCA in this group. XpressO’s lack of significant correlation with higher MoCA-sf scores makes it less suitable as a standalone tool for PSCD screening in outpatient stroke clinics. XpressO can be used to identify patients at risk for severe PSCD, but higher XpressO scores should not eliminate the possibility of PSCD in patients.
Abstract WMP55: Sociodemographic Factors associated with Experiences of Discrimination in a Diverse Cohort of Stroke Patients
Authors: Simons Tyler , Wang Mengxi , Cooksey Gail , Flake-Rojas Mariel , Okpala Munachi , Carter Caitylnn , Aquino Hernandez Ariana Victoria , Gonzales Louis , Yamal Jose-Miguel , Sharrief Anjail
Published: January 2025

Background and Purpose:
Historically disadvantaged and marginalized communities experience greater obstacles to health, higher stroke risk, and poorer stroke outcomes. Social determinants of health factors and experiences of discrimination have been linked to stroke risk, but more research is needed to understand the prevalence and the impact of experiences of discrimination for individuals with stroke. The purpose of this study is to estimate the proportion of individuals with stroke who report experiences of discrimination and to determine which patients are more likely to report everyday discrimination and discrimination in the healthcare setting.

Methods:
In this descriptive analysis, we evaluated 445 patients with a TIA, ischemic stroke, or hemorrhagic stroke who were enrolled in the randomized clinical trial, VIRTUAL (Video-based Intervention to Reduce Treatment and Outcome Disparities in Adults Living with Stroke or TIA) from March 29, 2022 to September 26, 2024. Reported experiences of everyday discrimination (EDD) or discrimination in the healthcare setting (HCD) were measured using validated perceived discrimination scales. Reported discrimination (score > 0) compared to no discrimination (score = 0) were compared across a distribution of sociodemographic variables including age, sex, race, ethnicity, language preference, educational attainment, and insured status.

Results:
EDD was reported in 92/435 (21.1%) of participants, while HCD was reported in 40/439 (9%). Reported EDD did not vary by age, sex, race, language preference, educational attainment, or insured status; however, there was a signal of higher EDD in patients of Hispanic vs non-Hispanic ethnicity (27% vs 18.5%, p= 0.056). Reports of HCD were higher in female vs male (12% vs 6.4%, p= 0.048) and non-English speaking patients (11.3% Spanish and 100% Other vs 8.7% English speaking, p <0.005). Reports of HCD also varied by race (37.5% Asian, 6.9% Black, 7.9% White, and 19% Other reported race; p <0.005).

Conclusion:
This analysis of a diverse cohort of stroke patients shows differences in reports of EDD vs HCD. Sociodemographic factors were not associated with EDD; however, there was a trend for more EDD reports by ethnicity (Hispanic). HCD was associated with several sociodemographic factors. Further investigation is needed to determine whether this reflects experiences across multiple communities and to what extent these experiences of HCD influence stroke risk, care, and outcomes.