bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP297: Focused Mouse Brain Irradiation Model to Define the Neurovascular Unit
Authors: Alcazar-Felix Roberto J , Srinath Abhinav , Bindal Akash , Malik Ahmed , Pearson Erik , Haro Fidel , Montas Dominic , Hage Stephanie , Pytel Peter , Awad Issam , Polster Sean P
Published: February 2024

Purpose:
This project aimed to develop a stereotactic radiosurgery mouse model of radiation-induced brain injury to study endothelial damage within the neurovascular unit (NVU). Classification of focal endothelial damage and the resulting inflammatory cascade has never been cataloged for assessing intrinsic changes versus extrinsic factors of inflammation at the NVU. The study of endothelial damage with invasive models, such as open transcranial injury or vessel occlusion, introduces multiple variables into the system that our model can help overcome to study secondary or systemic insults of the NVU.

Methods:
Using an X-ray image-guided radiation therapy system, mice were focally irradiated with 30, 45, and 70 Gy to a 5 mm brain target. Mice were followed up at 2, 4, 6, 12 and 18 weeks after irradiation with contrast-enhanced CT imaging for volumetric quantification of radiation effects. Brains were harvested for characterization by histology and immune-multiplexing of reactionary and inflammatory changes to the NVU. Whole coronal slides were scanned and analyzed using machine learning classifiers to quantify cell types within the NVU in the radiated vs. control hemispheres.

Results:
Radiation-induced changes such as telangiectasias, vessel hyalinization, and white matter necrosis were observed. An inflammatory response with a predominance of T cells was observed, as well as an increase in microglial cells and reactive astrogliosis. These changes were time and dose-dependent after radiation. Serial CTs allowed for determining the development of radiation damage, and the contrast enhancement was proportional to the degree of radiation-induced changes.

Conclusions:
This radiation model allows precise image-guided targeting with a steep radiation fall-off into surrounding tissues. The NVU’s response to focal insult of endothelial damage presents a novel method of brain injury to specifically study diseases associated with endothelial dysfunction.
Abstract TP298: Cellular Senescence and Microglial Dysfunction are Linked to Progressive Cognitive Deficits in the Chronic Phase of Ischemic Stroke
Authors: Khan Romeesa , Guzman Gary , Do Trang , Devlin Patrick , Di Gesu Claudia , Ahn John , Marrelli Sean P , Korf Janelle , Tan Chunfeng , McCullough Louise D , Venna Venugopal R , Ritzel Rodney
Published: February 2024

Improvements in acute stroke treatment, including endovascular thrombectomy and critical care management, have increased survival rates after stroke. However, many survivors have significant neurological deficits, as stroke remains one of the leading causes of long-term disability. Despite this, the chronic progression and long-term sequelae of ischemic stroke pathology remains woefully understudied. This study examined long-term progressive deficits in young adult male C57Bl/6 mice at 3 and 6 months after a 60-minute transient middle cerebral artery occlusion (MCAO) or sham surgery to identify secondary injury processes, and neuropathology of chronic stroke human brains. Depressive-like behavior persisted for 6 months post-stroke (PS) (p= <0.0001). Cognitive function progressively worsened from 3 to 6 months as seen by a continual reduction in the discrimination index in the novel object recognition task (p=.0063). Deficits in memory retention in mice 6-months PS were observed using the fear-conditioning test (p=.0084). Brain atrophy was evident by MicroCT imaging. Histopathological assessment revealed increased microglial activation in the hippocampus and frontal cortex in both mouse and human brains chronically after stroke. Interestingly, we also observed microglia activation proximal to apoptotic neurons in the brains of stroke mice, as shown by TUNEL assay. TUNEL co-labeling with a neuronal marker showed the same neuronal apoptosis in human samples from patients with chronic stroke, in both the hippocampus and thalamus. Disease-associated microglial (DAM) phenotypes were marked by both increased proliferative status and senescent-like phenotypes, including elevated production of cytokines and other proinflammatory molecules. Our findings demonstrate that experimental stroke accelerates inflammaging in the brain, which induces premature senescence within the chronic infarct microenvironment. Cellular senescence and chronic neurodegenerative signatures likely contribute to progressive cognitive impairment following stroke. The chronic and evolving neurological consequences of stroke may offer viable targets for delayed treatment strategies to reduce risk of vascular dementia and neurodegenerative disease.
Abstract TP308: FUS Contributes to Neurofunctional circRNAs Packaging Into Small Extracellular Vesicles Under Hypoxia Condition
Authors: Zang jiankun , Xu Anding , Lu Dan
Published: February 2024

Small extracellular vesicles (sEVs) contain abundant circular RNAs (circRNAs), contributing to a wide range of cellular processes. However, the precise process dictating the circRNAs packaging into sEVs remains unclear. This study revealed an innovative loading mechanism for particular circRNAs into sEVs during hypoxia, facilitated by the Fused in Sarcoma (FUS) protein and stress granules (SGs). We noted that the hypoxic sEVs has a higher abundance of FUS than that in normal sEVs. And the living cell images and immunofluorescence results indicate that, before loading into sEVs, FUS translocated from the nucleus and forms aggregate spots with marker protein CD63 in cytoplasmic SGs under hypoxia condition. Concurrently, by using the FISH staining and 5-EU click chemistry, we observed that FUS facilitates the specific cytoplasmic circRNAs recruit into SGs during hypoxia. Upon relief of hypoxic conditions, with the degradation of stress granules, the cytoplasmic FUS will gradually transport into sEVs with SGs-recruited circRNAs. Knocking out FUS dramatically disrupts the SGs recruitment of circRNAs to stress granules and significantly diminishes circRNA abundance in sEVs, leading to the accumulation of circRNAs in cytoplasm. Remarkably, by employing a newly transcribed RNA sequencing (RICK-seq), we found that the FUS medicated sEVs transport mechanism may be applicable to a class of neurofunctional circRNAs. Additionally, based on the observation of molecular docking and truncated peptides, we demonstrated that the zf_RanBP domain is essential for FUS interacting with specific circRNAs, which further highlights the critical role of FUS in the sEVs transport process of circRNAs during hypoxia stress. In general, our finding uncovered a FUS-medicated novel transport mechanism of specific circRNAs into sEVs during hypoxia, and indicate the potential therapeutic avenues for regulating the cargo of sEVs in hypoxia-related pathologies.
Abstract TP319: Time Course of Novel Hypothalamic Protein Sushi Repeat-Containing Protein X- Linked 2 Expression in a Rat Model of Subarachnoid Hemorrhage
Authors: Takemoto Yushin , Kanamaru Hideki , Huang Lei , Sherchan Prativa , Mukasa Akitake , Tang Jiping , Zhang John H
Published: February 2024

Background:
Hypothalamic injury after subarachnoid hemorrhage (SAH) is known to be associated with short- and long-term prognosis. Recently, a novel hypothalamic protein, Sushi repeat-containing protein X-linked 2 (SRPX2), was reported as a potential biomarker for hypothalamic damage after traumatic brain injury. However, there are no reports on SRPX2 in SAH, and its role is unknown. In this study, we investigated the expression of SRPX2 in the hypothalamus after SAH using a rat model of SAH.

Methods:
We made endovascular perforation model of SAH using 300g - 450g SD rats, and they were divided into two groups: Sham operated and SAH group. The endpoints were 3, 6, 12, 24, and 72 hours after SAH, and 7 days and 4 weeks after SAH, and physiological findings and neurological symptoms were measured. In addition, changes in SRPX-2 in the hypothalamic injury and related factors were examined immunohistochemically.

Results:
The SAH group showed significant neurological deterioration, and a significant decrease in body temperature after 3 h of SAH. Expression of SRPX2 in the hypothalamus was also significantly decreased at 3 h after SAH. However, it was not associated with changes in FJC- and TUNEL-positive cells suggestive of cell death or DHE expression suggestive of oxidative stress. On the other hand, OXT showed a significant decrease after 3 hours of SAH as measured by ELISA in serum from the jugular vein.

Conclusions:
This is the first study to investigate the expression of SRPX2 in the hypothalamus after SAH time course. Although our results suggest that SRPX2 may not be directly associated with hypothalamic injury after SAH, the fact that SRPX2 expression was decreased during the hyperacute phase and OXT and body temperature were also decreased at the same time suggests that SRPX2 may be indirectly associated with hypothalamic injury after SAH through regulation of endocrine and autonomic function in the hypothalamic-pituitary axis. Further studies are warranted to investigate the possibility that SRPX2 may be indirectly related to hypothalamic disturbances after SAH through endocrine and autonomic regulation of the hypothalamic-pituitary axis.
Abstract TP40: Identification of Domain-Specific Cognitive Phenotypes of Post Stroke Vascular Contributions to Cognitive Impairment and Dementia
Authors: Almane Dace N , Hermann Bruce P , Jones Jana E , Choi Tim J , Harkin Ciara D , Alexander Andrew L , Prabhakaran Vivek , Adluru Nagesh , Nair Veena A
Published: February 2024

Introduction:
Vascular contributions to cognitive impairment and dementia (VCID) are variably expressed following stroke. The purpose of this investigation is to identify the domain-specific cognitive phenotypes of VCID in the acute and sub-acute post-stroke interval measured using the Mark VCID battery.

Methods:
Mark VCID neurocognitive test battery was administered to 33 patients with incident ischemic stroke in the left (n=15), right (n=17), and bilateral (n=1) hemispheres including the anterior and middle cerebral artery territory, and 39 age and sex matched healthy controls (HC). Participants ranged in age from 42 to 88 years (Patient M=65.64 yrs, Control M=64.97 yrs). Patient group consisted of 17 males and 22 females, and the control group had 20 males and 13 females. Mean post stroke interval was 8 weeks (Range: 2.5 to 19 weeks). The test battery assessed: language (naming, fluency), perception (facial recognition, spatial orientation), psychomotor speed (digit symbol substitution), memory (word list, story recall), and attention (trails, number span). Normative test scores were converted to z-scores for assessment of between group differences using independent t-tests.

Results:
Patients with stroke performed significantly worse (p<0.05) than HCs on measures of language (semantic and phonemic fluency), perception (facial recognition and spatial orientation), and psychomotor speed (symbol digit modalities test) (Figure 1). There were no significant group differences in the scores of memory (Hopkins Verbal Learning, Craft Story) and attention tracking (Oral Trails A, Number Span).

Conclusion:
Cognitive abnormalities in these acute stoke patients represent impairments in diverse dominant (language) and non-dominant (perceptual/spatial) hemisphere cortical and subcortical (psychomotor speed) abilities. At the group level, the findings suggest a phenotype of VCID in patients with acute middle and anterior cerebral artery ischemic stroke.
Abstract TP49: State of the Florida Stroke Coordinator: Hospital Inventory Survey Insights
Authors: Sessa Joy , Gutierrez Carolina M , Gardener Hannah , Krigman Judith , Ampie Christina , Hylton Tara , Sobczak Evie , Rundek Tatjana , Romano Jose G , Gordon Perue Gillian L
Published: February 2024

Background:
Stroke coordinators (SC’s) are essential leaders of certified stroke centers which facilitate evidence-based stroke care, improving patient outcomes. Although this role has existed since the 1970’s, significant variability of responsibilities and staffing exists. Evidence based recommendations for SC staffing are scarce.

Purpose:
Utilizing the 2023 Florida Stroke Registry Hospital Inventory Survey (HIS), we describe current SC roles, responsibilities, and challenges in Florida.

Methods:
The Florida Stroke Registry (FSR), with state funding, tracks and measures Florida’s stroke center performance. FSR recently deployed the FSR HIS, a ten-part questionnaire examining various aspects of stroke program infrastructure. The survey was disseminated to 171 sites with 38 responses in the first wave. This is preliminary data from an HIS section focusing on SC staffing, workload, resources, and perceived challenges.

Results:
Responding sites all report a designated SC. Figure 1 describes SC’s Status (full vs. part-time), onboarding, and resources. Of note, only 35% of SC’s manage stroke full-time at a single site, SC turnover rate is high with 63% in the role <4 yrs. Stroke coordinators abstract for multiple databases, even with data abstractor support. In free-text responses, 58% (19/33) of SC’s cited lack of time and/or corporate structure for adequate program management as the biggest challenges in their role.

Discussion:
The preliminary study highlights significant challenges with high SC turnover, heavy workloads, and insufficient support. Stroke programs lack clear recommendations from certifying bodies for program personnel based on program volume. Future directions of FSR HIS include conducting additional dissemination waves, and an analysis of optimal stroke program staffing by cross-referencing certification level, patient volume and SC resources.
Abstract TP54: Ready to Ride
Authors: Stein Laura A , Scavicchio Karlie , Spahr Melissa , Hoey Colin , Sellers Michele , Rothstein Aaron , Ware Christopher
Published: February 2024

Background:
For stroke patients initially presenting to a primary stroke center with large vessel occlusions (LVO), treatment involves evaluation and subsequent transfer for thrombectomy. Our institution has utilized many of the AHA best practice strategies for improving door-in-door-out (DIDO), though targeting efficiency of the hand-off to the transporting team was not previously targeted.

Purpose:
This process sought to streamline hand-offs to the transporting team to improve overall DIDO times at our primary stroke center, specifically through decreasing the average transport team arrival to patient departure time.

Methods:
We identified multiple opportunities for intervention: improved documentation of Emergency Department departure time, standardized communication with transport team, and need for consistent path to helipad. A standard method of communicating transport team estimated arrival was established to ensure readiness of emergency department staff and patient for transport to helipad. A structured report including the required paperwork was created for all transfers between the emergency department providers and transport team. Lastly, a consistent path to the helipad itself was identified. A Mann Whitney Test was used to compare the means of door in to transport departure and transport arrival to transport departure. Transport departure was used as the standard for door out.

Results:
Mean for door to transport departure pre intervention was 126.47 (STD of 33.13). Post-intervention was 126. 43 with STD of 56.62. This was not significant (p=0.76). Mean for transport arrival to transport departure prior to intervention was 26.72 minutes (STD of 8.44) and post intervention was 19.86 (STD of 16.65). This was significant (p=0.01).

Conclusions:
Standardizing hand-offs and improving transport efficiency and communication are feasible interventions in overall efforts to improve care delivery and efficiency. Early data suggests these interventions decrease time between transport arrival and door out. Further work is necessary to assess impact on DIDO.
Abstract TP55: A Statewide Quality Improvement Project: Identifying Disparities in Dysphagia Screening for Stroke Patients
Authors: Anderson Nicky , Fujii Ally
Published: February 2024

Objectives:
One of the principal cornerstones of the Minnesota Department of Health’s Stroke Program is quality improvement. Minnesota Primary (PSC) and Comprehensive Stroke Center (CSC) hospitals have consistently demonstrated performance below the national benchmark (76%) for dysphagia screening. We formed a workgroup comprised of stroke coordinators from across the Minnesota Stroke System to stratify the data by race, ethnicity, and insurance status and collectively identify ways to improve dysphagia screening for stroke patients.

Methods:
In 2021, MN Stroke Registry data was analyzed for dysphagia screening performance and compliance. Data was stratified by race, ethnicity and insurance status to assess for variance in performance. Disparities by patient race/ethnicity and an overall underperformance on this measure in MN compared to hospitals nationwide was identified. Work group members developed an action plan to improve resources and increase dysphagia screening performance.

Results:
In Minnesota, Asian (63%) and African American (68%) stroke patients are less likely to be screened for dysphagia than stroke patients overall (76%). Patients on Medicaid were also slightly less likely to receive dysphagia screening. Statewide initiatives included: guidance on stratifying site-specific data; creation of Impaired Swallowing Education for medical providers accessible on YouTube, cultural considerations, and electronic health record best practices; facilitators and barriers were reported and shared.

Conclusions:
The overall percentage of dysphagia screening compliance has remained steady at 77%. Continuation of the QI project will focus on identifying group participants that are actively engaged and implementing programmatic changes to improve dysphagia screening and identify disparities within their organizations. Education was successfully disseminated to 136 hospitals across the Minnesota Stroke System with over 450 views on YouTube. The work group is exploring further development of data disaggregation standards, specific to the diverse and growing populations of Minnesota. This is a vital step to develop more effective strategies and interventions that directly address health disparities.
Abstract TP58: Stroke Recognition Task Force: Increasing Early Activation of Inpatient Stroke Codes
Authors: Marmo Joanna M , Mulchan Nicholas , giglio brandon
Published: February 2024

Background:
1 in 5 strokes occur in the hospital. Patients with in-hospital stroke have increased vascular risk factors, delayed time to recognition, and increased mortality compared to patients with community-onset stroke. All staff should be able to recognize and initiate management of patients with a suspected acute stroke.
Purpose
The goals of this project were to increase early activation of inpatient stroke codes and confidence levels related to the recognition of stroke and management of patients during a code.

Methods:
An education program, providing unit specific information, was provided to each inpatient unit at an academic medical center. A survey was created for learners to take before and after the education session; including questions regarding symptom recognition, how to activate a stroke code, and tasks required following activation. Additional questions included self-assessment of the learner’s confidence level in different aspects of stroke care, including stroke recognition and management. To assess time to activation, data related to inpatient stroke code activations was analyzed pre- and post-intervention. Data included symptom discovery and stroke team activation time gathered from the electronic medical record.

Results:
Data from 119 codes was reviewed. Prior to intervention, only 50% of inpatient stroke codes were activated within 10 minutes of symptom discovery. Following intervention, 75% of inpatient stroke codes were activated within 10 minutes of symptom discovery. There were 61 pre-session survey responses and 39 post-session. Before the session, 56.1% of participants were slightly or moderately confident in identifying stroke, but after the session, 80.5% of participants were very or extremely confident in identifying stroke. Before the session, 81.8% of participants did not feel comfortable managing a patient during a code, but after the session, 95% of participants felt comfortable.

Conclusion:
An education session for hospital staff can increase knowledge and confidence level in the recognition of stroke and their management of patients. This curriculum has potential to be used nationally to reduce delays to diagnosis, increase usage of acute therapies and reduce mortality associated with in-hospital stroke.
Abstract TP72: Capturing the Effects of Non-Body Weight Supported Backward and Forward Treadmill Training on Chronic Post-Stroke Lower Extremity Spasticity and Walking Speed
Authors: Xia Christina , Drury Colin , Awosika Oluwole
Published: February 2024

Introduction:
Stroke-related walking impairment significantly impacts ambulatory independence and is a major public health issue. While the factors influencing walking impairment after stroke are multifactorial, the role of lower extremity spasticity is one factor that remains unsettled. For example, while past studies have suggested that increased lower extremity tone led to maladaptive walking patterns, others have suggested that spasticity may improve walking ability by compensating for weakness. Hence, the objective of this exploratory study was to determine the effects of serial non-body weight backward (BLTT, n=19) and forward (FLTT, n=21) locomotion treadmill training on lower extremity spasticity (LES). We hypothesized that both BLTT and FLTT will improve LES, but to a greater extent with BLTT.

Methods:
Data from a recently completed RCT (NCT04553198) consisting of 40-community-dwelling stroke survivors with mild-moderate walking impairment, who completed nine 30-minute training sessions (3 per week x 3) were used for this secondary exploratory analysis. Spasticity was assessed (quadricep, hamstrings, gastrocnemius, soleus muscles) by a trained therapist blinded to study intervention using the modified Ashworth Scale (MAS) and 10mWT was used to assess the relationship to walking speed.

Results:
Training resulted in reduced spasticity in the quadriceps (p = 0.01), but not in the other three muscle groups. Contrary to our working hypothesis, FLTT drove the improvement in spasticity in both quadriceps and hamstrings (p <0.01 and p = 0.02, respectively). Both groups demonstrated improvement in walking speed (p< 0.0001), but no correlation between change MAS and walking speed was observed.
Abstract TP77: Stroke Rank Order Correlation but Moderate Absolute Value Drift Between Early Day 2/4 and Day 90 Stroke Outcome Scales: mRS, BI, and NIHSS
Authors: Taleb Shayandokht , Lee Jenny J , Sanossian Nerses , Starkman Sidney , Conwit Robin , Hamilton Scott , Saver Jeffrey L
Published: February 2024

Background:
In acute stroke trials, the three most commonly used outcome scales are the modified Rankin Scale (mRS) to assess global disability, the Barthel Index (BI) to assess instrumental activities of daily living, and the National Institutes of Health Stroke Scale (NIHSS) to assess neurologic deficit severity. The value of early scale assessments to forecast 3-month disability outcomes has not been formally investigated.

Methods:
In this cohort study of patients with acute ischemic stroke (AIS) in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) Phase 3 trial, we assessed the performance of day 2, 4, and 30, BI, and NIHSS to forecast their day 90 counterparts using correlation coefficients and absolute differences.

Results:
Among 1041 with AIS, mRS on d2 (r=0.67) and d4 (r=0.72) showed strong correlation and mRS on d30 (r=0.89) very strong correlation with d90 mRS. However, value shifts were common. For example, d4 mRS exactly matched d90 mRS in only 35.8%, while 40.2 % had better and 24 % had worse outcomes. D4 BI exactly matched d90 BI in only 41.2%, while 48.5% had better and 11.2% had worse outcomes. For NIHSS, d4 exactly matched d90 value in only 20.5%, while 57.9% had better and 22.6% had worse outcomes. (Figure)

Conclusions:
mRS, BI, and NIHSS outcomes as early as days 2 and 4 post-stroke correlate strongly with their longterm, 3m outcome rank ordering but only moderately with their absolute values. Delineation of this outcome trajectory provides a foundation for imputing final patient disability, ADL, and deficit outcomes in clinical trials and quality improvement programs.
Abstract TP78: Characteristics of Verbal and Non-Verbal Cognitive Function in Post-Stroke Aphasia Based on Language-Cognition Neuropsychological Processing Model
Authors: Li Siqi , Zhang Yumei
Published: February 2024

Introduction:
Post-stroke aphasia (PSA) patients have different levels of phonetic, lexical, semantic, syntactic, and other linguistic domain impairment, and accompanied by non-verbal cognitive impairment. However, the association between verbal and non-verbal cognitive functions is not fully understood.In this study, we used the Chinese Aphasia Language Battery (CALB) and Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) to fully evaluate the characteristics of verbal and non-verbal cognitive function impairment in PSA patients.

Methods:
A total of 105 stroke patients were recruited in this study. Language and non-linguistic cognitive impairments were evaluated by CALB and LOTCA, respectively. Patients in the PSA group were subdivided into the fluent aphasia group (FAG) and the non-FAG group. Potential confounders were adjusted in the analysis of covariance. Partial correlation analysis between the subscores of CALB and LOTCA was also performed.

Results:
This study showed that PSA patients had worse speech analysis ability, vocabulary processing ability, semantic processing ability, syntactic structure conversion ability, and non-verbal cognitive performance(P<0.001). Moreover, the scores of phonetic decoding, phonetic vocabulary production, noun category classification, total LOTCA, orientation, visual perception, motor use, and thinking operation were lower in the non-FAG compared with the FAG (p<0.05). The total score of LOTCA was positively correlated with the aphasia quotient (r=0.637, P<0.001) and scores of speech analysis ability, vocabulary processing ability, semantic processing ability, and syntactic structure conversion ability (r>0; P<0.0005).

Conclusions:
Based on the language-cognition neuropsychological processing model, this study adopted a comprehensive verbal and non-verbal cognitive assessment set of tests, and found that PSA patients have extensive phonological, lexical, semantic, syntactic, and grammatical processing disorders. Moreover, PSA patients often have more extensive and serious non-verbal cognitive impairments, and the severity of aphasia is significantly positively correlated with the degree of nonverbal cognitive impairment.
Abstract TP83: Outcomes of the Relationship Between Telehealth and Caregiver-Stroke Survivor Dyad, in the Rehabilitation Phase: A Systematic Review
Authors: Bartoli Davide , Pucciarelli Gianluca , Petrizzo Antonello , Vellone Ercole , Alvaro Rosaria
Published: February 2024

Background:
The success of post-stroke rehabilitation depends on the cooperation of many components such as: severity of the stroke, speed with which treatment begins, skills of the rehabilitation team, cooperation of the survivor with family and friends. Telerehabilitation (TLR) involves home rehabilitation with a nurse or physician, who evaluates and supports survivors remotely and in remote locations through the use of telecommunication devices. Although several studies investigate the role of TLR only on survivors or only on caregivers, to our knowledge no reviews analyzed the role of the caregiver and stroke survivor in the home-based TLR phase.

Aims:
to examine studies involving the effect of TLR, telehealth, and tele-support on the dyad stroke survivor and caregiver in relation to psychological, physical, and social dimensions.

Methods:
It was conducted and reported following checklists for Reviews of PRISMA 2020. Critical evaluation of the quality of the studies included in the review was performed with the Checklists of the Joanna Briggs Institute. We performed a comprehensive search of the following electronic databases:
PsycInfo, CINAHL, Eric, Ovid, PubMed, Scopus, Cochrane Central and Web of Science.
Included studies of stroke survivors-caregiver dyads after the discharge of stroke survivors from hospital and rehabilitation hospital who were without severe cognitive impairment and lived in their own homes.

Results:
2290 records were identified after removal of duplicates, 501 articles were selected by title and text abstract, only 21 met the inclusion criteria. No studies were excluded based on the Critical Quality Assessment tool. Were 7 RCTs, 1 cohort study, 4 quasi-experimental and 9 qualitative. The results were divided into qualitative and quantitative outcomes.

Conclusions:
11 effect domains were defined: functional, psychological, burden, social, general health and self-efficacy, family function, quality of life, health care utilization, preparedness, quality of care and relationship to technology. The study contributes to the implementation of survivor-caregiver dyadic interventions, to improve the coordination of assistance in transitional care by opting for a telehealth path that best meets the needs of dyad.
Abstract TP96: Association Between Infarct Volume, Neighborhood-Level Deprivation, and Outcomes in Pediatric Stroke
Authors: Pai Akshat M , Adekunte Shadia , Robertson Amanda , Abdalla Alhusain , Nichol Daniel , To Teresa , Deveber Gabrielle A , Ertl-Wagner Birgit , Kassner Andrea , Dlamini Nomazulu
Published: February 2024

Introduction:
Recent studies in adults have reported an association between neighborhood-level deprivation, infarct volume and outcome. However, this is yet to be investigated in pediatric arterial ischemic stroke (AIS). Our study aimed to assess the relationship between neighborhood-level deprivation, infarct volume, and neurological outcome in children diagnosed with AIS.

Methods:
We conducted a study of a consecutive cohort of children aged > 28 days-18 years and diagnosed with AIS between 2004 and 2019 at a comprehensive stroke center. Patient demographic, clinical characteristics and neighborhood material deprivation data including household income, parental educational attainment, the proportion of single-parent families, and housing quality were collected. Lesion volumes were determined by conducting semi-automatic segmentation of diffusion-weighted MRI brain scans at stroke presentation. Neurological outcome was assessed using the Pediatric Stroke Outcome Measure Severity Classification System wherein poor outcome was defined as moderate-to-severe deficit at 18 months post-stroke. Wilcoxon rank sum test was conducted.

Results:
Seventy-two patients were included in the study (62% male, median age of stroke onset 6.1 years [IQR 1.0-12.7]). 39% of patients were White, 72% lived in an urban region, and 64% in highly deprived neighborhoods. 70% of patients arrived within 6 hours from onset of stroke. Cardiac disease and other risk factors including infection and head trauma represented the most common risk factor. 55% presented with moderate stroke severity (as per the PedNIHSS). Median lesion volume was 14 cm
3
(IQR 2-51) and a mean infarct volume of 3% was reported. Race, rurality, and neighborhood-level material deprivation were not significantly associated with either percent infarct volume or neurological outcome; however, percent infarct volume was significantly associated with neurological outcome at 18 months post-stroke (W = 79,
p
= 0.025).

Conclusion:
Our study findings confirm the relationship between infarct volume and pediatric AIS outcomes. Future multi-center studies are warranted to further understand the interplay between material deprivation, infarct volume, and post-AIS neurological outcomes in children.
Abstract WMP101: Global Burden of Stroke Attributable to High BMI in 38 OECD Countries From 1990-2019: A Benchmarking Systematic Analysis
Authors: Cortorreal Javier Rafael , Asif Maryam , Dadhania Khush , Chhayani Hiren , Ahmed Danish , bhandal Sukhjiwan Singh , sajeev Krishna , patel Anandkumar , Elassar Samar , Aramin Mohammed , Thota Anjani Kumar , Gadamidi Vinay Kumar , Patel Tirath , AMIN Vishrant P , Desai Hardik Dineshbhai
Published: February 2024

Background:
The global burden of stroke remains a significant public health challenge, with high body mass index (BMI) emerging as a notable and modifiable risk factor in Organization for Economic Co-operation and Development (OECD) countries.

Method:
Using Global burden of disease tool, deaths and disability adjusted life years due to Stroke attributable to High BMI were assessed by age, sex, year across the 38 OECD countries from 1990-2019.

Result:
The total number of deaths saw a decline from 148,031 (95%UI 85,206-219,328) in 1990 to 143,105 (95%UI: 85,383-209,533) in 2019. The annual percentage change (APC) in the total number of DALYs exhibited a decrease of 1% between 1990-2019. Notably, the most substantial increase in APC for deaths was observed in Turkey at 129%, followed by Mexico at 95% from 1990-2019. Conversely, Estonia displayed the most significant decrease in APC at 63%. In relation to DALYs, Turkey experienced the highest APC at 99%, followed by Costa Rica at 85% from 1990-2019. In 2019, the age group of 75-79 exhibited the highest number of deaths (22,709) while the age group of 65-69 had the highest DALYs (553,284). In terms of gender differences, males observed a 5% increase in APC for deaths, whereas females witnessed a 10% decrease in APC from 1990-2019.

Conclusion:
The global burden of stroke attributable to high BMI in OECD countries highlights the urgent need for comprehensive strategies to address the intertwined challenges of obesity and stroke. Efforts to prevent and manage obesity, coupled with targeted interventions to mitigate stroke risk factors, hold the promise of reducing the human, societal, and economic toll of this prevalent and debilitating condition.
Abstract WMP103: Tightening of the Stroke Belt
Authors: Termeie Orly G , Saver Jeffrey L
Published: February 2024

Background:
Higher stroke mortality in the Southeastern United States has been recognized for over 80 years, but recent trends from in Stroke Belt (SB) vs non-SB stroke death rates have not been well delineated.

Methods:
We analyzed stroke-related annual age-adjusted mortality rates (AAMR) in the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database from 1999-2019, comparing the 8 SB states (Alabama, Arkansas, Georgia, Louisiana, Mississippi, North Carolina, South Carolina, and Tennessee) and 42 non-SB states among all individuals and subgroups of age, sex, race-ethnicity, and urban-rural. AAMRs reported per 100,000 individuals.

Results:
Throughout the 1999-2019 period, AAMRs were higher in the SB than non-SB. Both SB and non-SB states showed rapid AAMR decline from 1999 - 2009, then slow decline 2009-2014, and plateau 2014-2019. Yet, SB AAMR declined more rapidly. AAMRs in 1999, 2009, and 2019 in the SB were 122.60, 80.54, and 73.52; in the non-Stroke Belt 100.84, 64.14, and 61.35). As a result, the number of SB states with substantially elevated AAMR compared with non-SB states fell from 7 in 1999 to 6 in 2009 and 2 (MS, TN) in 2019 (Figure). Age, sex, and urban-rural subgroup trends resembled the overall population. Yet, race-ethnic variations were noted. Throughout the study period in the SB, Black individuals had the highest AAMRs but had a steeper decline than White individuals, with the gap narrowing from 49.50 (163.06 vs 113.56) in 1999 to 28.45 (96.97 vs 68.52) in 2019. AAMRs for Hispanic and Asian individuals were lower than White individuals throughout the study period in the SB and dropped more steeply for Asian (76.18 to 46.76) than Hispanic individuals (54.50 to 35.61).

Conclusions:
Stroke mortality declined more steeply between 1999-2019 in the Southeastern US than the rest of the country. Substantial SB race-ethnic disparities persist, with AAMRs highest in Black, intermediate in White, and lowest in Asian and Hispanic individuals.
Abstract WMP105: Association of Comorbidities, Stroke Etiology, and Polygenic Risk Score in Japanese Ischemic Stroke Patients
Authors: Shimoyama Takashi , Matsuda Koichi , Kamatani Yoichiro , Yamaguchi Hiroki , Kimura Kazumi
Published: February 2024

Background:
Previous trans-ancestry genome-wide association studies (GWAS) of stroke reported 32 stroke risk loci, which were conducted predominantly in populations of European ancestry. The aim of this study was to examine the association of comorbidities, stroke etiology, and polygenic risk score (PRS) for stroke in the Japanese population.

Methods:
A total of 19702 ischemic stroke patients (n= 12241 male and n= 7261 female, median age 71 years old) were analyzed. We selected 19 significant stroke loci from a set of 32 stroke-related genes to construct the PRS in the Japanese population. The multivariate logistic regression model was conducted to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for comorbidity and stroke etiology across the PRS.

Results:
Compared with the lowest quintile PRS, the ORs (95%CIs) of atrial fibrillation/flutter at the top PRS quintile was significantly higher independently from traditional stroke risk factors (ORs, 2.13; 95%CIs 1.69-2.68). This significant association remained through continuous PRS (ORs, 1.59; 95%CIs 1.10-2.31). Other traditional stroke risk factors were not significantly associated with increased PRS. Similarly, we also investigated the association between the PRS and stroke subtype in patients with identified stroke etiology based on the TOAST criteria (n=6608). Continuous PRS was significantly higher in patients with cardioembolism by multivariate logistic analysis (ORs 1.45; 95%CIs 1.14-1.85). Conversely, continuous PRS was significantly lower in patients with small vessel occlusion (ORs 0.85; 95%CIs 0.73-0.98).

Conclusion:
In Japanese ischemic stroke patients, PRS for stroke was significantly associated with atrial fibrillation/flutter and cardioembolism. Our findings suggest that the importance of a PRS for stroke may be helpful for identifying high-risk sources of cardioembolism including atrial fibrillation in the Japanese population.
Abstract WMP107: Exploration of the Inflammatory Profile of Gluteofemoral Adipose Tissue Distribution Supports Role of Targeting Inflammation to Further Decrease Cardiovascular Risk
Authors: Myserlis Evangelos Pavlos , Georgakis Marios K , Konieczny Marek , Omarov Murad , Mayerhofer Ernst , Parodi Livia , Rosand Jonathan , Anderson Christopher D ,   NINDS-SiGN
Published: February 2024

Introduction:
Recent evidence suggests that body fat distribution is associated with cardiovascular risk. We have previously shown that gluteofemoral adipose tissue (GFAT) distribution is associated with a favorable cardiovascular risk profile. Given the emerging role of inflammation in cardiovascular health, we explored the inflammatory profile of GFAT and the possible mediatory role of inflammatory cytokines underlying the association between GFAT and cardiovascular risk.

Methods:
As previously described, utilizing GWAS data and univariable Mendelian Randomization (MR) analyses we explored the association between genetically proxied GFAT (n= 37,750) and 6 vascular outcomes [ischemic stroke (IS) (n=62,100), large artery stroke (LAS) (n=6,399), small vessel stroke (SVS) (n=6,811), coronary artery disease (CAD) (n=181,522), lacunar stroke (n=6,030), and carotid intima media thickness (cIMT) (n=45,185)]. We also performed univariable MR between GFAT and 40 circulating inflammatory markers (n=75,000) and derived the significant profile after FDR correction. We then explored the mediatory effect of the inflammatory profile on the cardiovascular outcomes after performing two-step mediation MR. Cytokines that showed significant univariable MR associations with both GFAT and the vascular outcomes were considered candidate mediators.

Results:
Genetically proxied GFAT was associated with decreased risk of IS (p=0.006), LAS (p=0.016), SVS (p<0.001), CAD (p<0.001), and lacunar stroke (p=0.001), and lower mean cIMT (p=0.001). GFAT showed significant association with 9 inflammatory cytokines
(Figure)
. HGF was a candidate mediator underlying the GFAT-CAD association and IL-2 showed significant suppression effect in the GFAT-cIMT axis (β
GFAT-cIMT
=-0.07, p=0.001; β
IL-2-cIMT
=0.01, p=0.0126).

Conclusion:
In the context of a favorable body fat distribution, targeting IL-2 may further enhance the protective role of GFAT on cardiovascular risk.
Abstract WMP108: Association of Circulating Markers of Inflammation to Baseline and Progression of Carotid Artery Intima-Media Thickness
Authors: Baradaran Hediyeh , Pinheiro Adlin , Romero Jose R
Published: February 2024

Introduction:
There is strong evidence of an association between systemic inflammation and ischemic stroke. While the exact mechanism underpinning that association is unclear, there is evidence that systemic inflammation contributes to atherosclerosis progression. One measure of subclinical atherosclerosis, carotid artery intima-media thickness (CIMT), is independently associated with ischemic stroke. Because of mixed data on the association between systemic inflammation and CIMT progression, we sought to evaluate this relationship in a prospective cohort study.

Hypothesis:
Baseline elevation in circulating markers of inflammation are associated with CIMT progression in the Framingham Heart Study cohort.

Methods:
Among participants with two carotid ultrasounds (n=2350) about 10 years apart, 2,269 had data available on circulating markers of inflammation. Multivariable linear regression was used to assess the association between circulating markers of inflammation with internal carotid artery (ICA) CIMT. Analyses were adjusted for age, sex, hypertension, diabetes, APOE4, and body mass index (BMI), and baseline IMT.

Results:
Participants with higher baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6), intracellular adhesion molecule, p-selectin, lipoprotein-associated phospholipase A2 (LPa) activity, homocysteine, isoprostanes (ISO), and CD40 ligand had significantly higher rates of ICA IMT progression adjusting for age, sex, hypertension, diabetes, APOE4, BMI, and baseline ICA IMT (Table). Participants with higher levels of CRP, IL-6, OPG, p-selectin, LPa activity, and ISO had greater follow-up ICA IMT adjusting for age, sex, hypertension, diabetes, APOE4, and BMI.

Conclusion:
Specific markers of inflammation are associated with increased later life carotid intima media thickening and carotid atherosclerosis progression, supporting a link between systemic inflammation and cerebrovascular disease.
Abstract WMP109: Argonaute 2 Regulates Adult Neurogenesis and Oligodendrogenesis After Stroke
Authors: Liu Xianshuang , Chopp Michael , Wang Xinli , Cui Xu , Landschoot-Ward Julie , Wei Min , Zhang Zheng Gang
Published: February 2024

Background:
Stroke-induced neurogenesis and oligodendrogenesis contribute to improvement of neurological function after stroke. However, mechanisms underlying post stroke neurogenesis and oligodendrogenesis warrant investigation. Argonaute (Ago) genes, the major components of the RNA-induced silencing complex, regulate microRNA (miRNA) function for post-transcriptional gene silencing. The present study investigated the role of neural stem cell (NSC) specific Ago2 after stroke.

Methods and Results:
Compared to non-stroke NSCs, stroke significantly upregulated Ago2 expression in subventricular zone (SVZ) NSCs. Using adult male mice with conditional ablation of Ago2 in Ascl1 lineage NSCs (Ago2 cKO), we then examined NSC function in neurogenic regions of the SVZ and hippocampus. Under non-ischemic conditions, compared to wild-type littermates (WT), Ago2 cKO mice showed significantly reduced neuronal and oligodendrocyte differentiation of NSCs measured by newly generated neuroblasts (BrdU
+
/DCX
+
, 12±7/mm
2
cKO vs 32±11/mm
2
WT, n=3/group, p<0.05) in the neurogenic areas and new mature oligodendrocytes (BrdU
+
/CC1
+
, 20±4/mm
2
cKO vs 40±16/mm
2
WT) in the corpus callosum. In addition, Ago2 cKO mice exhibited the learning and memory impairments. Moreover, Ago2 cKO mice subjected to middle cerebral artery occlusion exhibited significantly reduced sensorimotor functions as measured by the adhesive test, foot-fault test, and modified neurological severity scores compared to WT ischemic mice. Mechanistically, mRNA and miRNA sequencing and bioinformatics analyses showed that ablation of NSC Ago2 deregulated many neurogenic genes involved in the sonic hedgehog (Shh), Notch and TGFβ signaling pathways, and altered Ago2-bound miRNAs that potentially target Shh (miR17-92 cluster), Notch (miR-124, miR-146a) and and TGFβ (miR-21, miR-200c) pathway genes, suggesting that Ago2 regulates neurogenesis and oligodendrogenesis via these miRNA-mRNA interactions.

Conclusions:
Our data demonstrate an essential role of Ago2 in adult neurogenesis and oligodendrogenesis, and also provide potential therapeutic targets of Ago2-bound miRNAs for improvement of neurological outcomes after stroke by enhancing NSC function.
Abstract WMP11: Intravenous Thrombolysis in Patients Without versus With Visible Occlusion: A Secondary Analysis From the AcT Trial
Authors: Siddiqi A. Zohaib , Ignacio Katrina H , Bala Fouzi , Ademola Ayoola , Tkach Aleksander , Buck Brian H , Catanese Luciana , Hunter Gary , Dowlatshahi Dar , Zafar Atif , Field Thalia S , Appireddy Ramana , Shamy Michel , Wadhwa Ankur , Sajobi Tolulope , Swartz Richard H , Demchuk Andrew M , Almekhlafi Mohammed A , Menon Bijoy K , Singh Nishita
Published: February 2024

Background:
Around 70% of patients who present with acute ischemic stroke(AIS) have no visible occlusion on baseline imaging. In this post-hoc analysis from the AcT trial, we aimed to assess if there is a difference in safety/efficacy of intravenous thrombolysis in patients presenting with AIS symptoms with no visible occlusion(NVO) versus with visible occlusion(VO). We further sought to determine if this effect differed between tenecteplase and alteplase in the NVO group.

Methods:
Primary outcome was symptomatic intracerebral hemorrhage(SICH) within 24 hours. Secondary outcomes included modified Rankin Scale(mRS) 0-1, mRS 0-2, ordinal mRS at 90-120 days, and hemorrhage on imaging as defined by Heidelberg bleeding classification. Mixed effects regression model with quasi Poisson link was used to estimate NVO effect while adjusting for age, sex, NIHSS, thrombolytic type, and onset to needle time.

Findings:
Of the 1577 patients, 1470(93.2%) patients who received thrombolysis within 4.5h and with available baseline CT angiogram were included in the study. Of these, 479 (30.4%; 247: tenecteplase and 232: alteplase) were in NVO and 991 (69.6%; 509: tenecteplase and 482: alteplase) were in VO group. Patients in NVO group were younger (median 71y vs 75y), with less severe strokes (median NIHSS 6 vs 12). Patients in NVO group had significantly lower rates of death as compared to VO group (8.1% vs 19.1%, adjusted risk ratio(adjRR)1.5, 95%CI:1.0-2.6). There was no difference in rates of SICH (2.3% vs 3.6%, adjRR 0.99, 95%CI:0.5-2.1) or rates of 90-d mRS 0-1 (43.3% vs 31.9%, adjRR 1.0, 95%CI:0.8-1.1). All safety and efficacy outcomes were similar between alteplase and tenecteplase in NVO group.

Interpretation:
Thrombolysis is just as safe in patients with AIS symptoms with NVO as compared to those with VO on baseline imaging. When thrombolysis is given, there is no difference in outcomes between these group by thrombolytic type.