bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 139: Association between Cerebral Amyloid Angiopathy and Non-Traumatic Subdural Hemorrhage
Authors: Andres Wells , Bruce Samuel , Merkler Alexander , Iadecola Costantino , Chiang Gloria , Kamel Hooman , Zhang Cenai , Murthy Santosh
Published: January 2025

Introduction:
Cerebral amyloid angiopathy (CAA) is a common cause of intracerebral hemorrhage in elderly patients. Whether CAA is associated with isolated subdural hemorrhage (SDH), without an accompanying intracerebral hemorrhage, remains unclear. We therefore tested this relationship in a large, heterogeneous sample of patients from across the US.

Methods:
We performed a retrospective cohort study using administrative claims data from hospitalizations in 11 states in the US between 2016 and 2019. Our study population was all hospitalized patients 50 years of age and older, consistent with the Boston criteria v2.0 age cut-off for the diagnosis of CAA. We divided this population into 3 groups: (a) those with a diagnosis of CAA, (b) those with other cerebrovascular disease without CAA, and (c) those without CAA or other cerebrovascular disease. The main outcome was a first-documented, isolated, non-traumatic SDH; we did not count SDH cases with a concurrent traumatic brain injury. The exposures and outcome were identified using previously validated
ICD-10-CM
diagnosis codes. Using Cox regression analyses, we compared the risk of incident SDH among the three groups after adjustment for demographics and comorbidities. In pre-specified sensitivity analyses, patients with a diagnosis of dementia at baseline were excluded.

Results:
Among 8.5 million hospitalized patients, 2,335 had CAA and 600,646 had other cerebrovascular disease. During a median follow up of 2.0 years (IQR, 1.0-3.9), incident SDH occurred in 34 (1.5%) patients with CAA, 3,552 with other cerebrovascular disease (0.6%), and 35,425 (0.4%) without CAA or other cerebrovascular disease. In adjusted Cox regression analysis, there was an increased risk of incident SDH seen for CAA (HR, 3.1; CI, 2.2-4.4) and prevalent cerebrovascular disease (HR, 1.4; CI, 1.3-1.5). Findings were similar in sensitivity analyses excluding patients with dementia.

Conclusion:
In a large, heterogeneous cohort, we found that CAA was associated with a 3-fold heightened risk of SDH. This risk appeared higher than that seen in patients with prevalent cerebrovascular disease. These findings further add to emerging evidence that CAA is a novel risk factor for isolated non-traumatic SDH.
Abstract 146: Data Independent Acquisition Mass Spectrometry Identifies Novel Plasma Protein Biomarkers that Distinguish Transient Ischemic Attack from Stroke Mimics
Authors: Misra Shubham , Jang Wooyoung , Kumar Prateek , Lam TuKiet , RANGARAJU Srikant
Published: January 2025

Introduction:
Patients with transient ischemic attack (TIA) and those with stroke mimics (MIM) are often difficult to distinguish in emergency room (ER) settings. While TIA patients are at an increased risk of stroke, MIM do not need stroke-related management. Biomarkers that distinguish TIA from MIM could guide risk-stratification and resource utilization in acute stroke care.

Objectives:
We undertook an exploratory proteomics study to nominate differentially enriched proteins (DEPs) as plasma biomarkers that distinguish TIA from MIM.

Methods:
Plasma samples from TIA and MIM were obtained from a prospective plasma repository (2010 to 2014) in which blood samples were obtained from adults ≥18 years of age who presented to the ER with acute neurological symptoms. We performed data-independent acquisition (DIA) label-free quantitative mass spectrometry (Orbitrap Astral MS) on age-matched TIA (n=20) and MIM (n=20) plasma samples, pooled into 4 TIA and 4 MIM plasma pools (5 cases per pool). Data were log
2
transformed, and random imputation for proteins with ≤50% missing values was performed (Perseus 2.0.11). We applied quantile normalization and identified DEPs using ±1.5-fold change and an unadjusted p-value <0.05, as well as the Boruta random forest-based machine learning algorithm. We conducted gene ontology analysis of the upregulated proteins in TIA (clusterProfiler package in R 4.3.2). We further validated these DEPs using data from our previous SomaScan proteomics study on the same samples.

Results:
We quantified 956 proteins, of which 524 proteins had ≤50% missing values and >90% had a coefficient of variation <20%. We identified 40 DEPs, with 32 increased and 8 decreased in TIA compared to MIM. Gene ontology highlighted pathways related to the extracellular matrix, intracellular lumen-related compartments, immune response, complement system, and reproductive processes in proteins increased in TIA (Figure 1). External validation identified 789 overlapping proteins between the DIA-MS and SomaScan platforms. Increased levels of IGFBP2, FTL, and RNASE1 in TIA compared to MIM were validated (Figure 2).

Conclusions:
Our discovery proteomics study highlights the potential of DIA-MS proteomics as a valuable tool for discovering novel protein biomarkers to distinguish TIA from MIM. These findings warrant validation in larger, longitudinal studies.
Abstract 149: Lessons Learned from the Veterans Health Administration National Telestroke Program’s Inpatient Subacute Telestroke Consult Service: A Mixed-Methods Study of Implementation Successes&Challenges
Authors: Stamm Brian , Calcatera Samantha , Spontak Katrina , Musser William , HERMANN LISA , Williams Linda , Damush Teresa
Published: January 2025

Introduction:
Acute telestroke connects stroke experts with rural or under-resourced hospitals to aid in emergent stroke decision-making. Few studies have evaluated subacute inpatient telestroke programs that focus on subsequent stroke management. We evaluated the implementation of the Veterans Health Administration (VHA) subacute telestroke consult service launched in 2022 by the National Telestroke Program (NTSP).

Methods:
Program implementation was assessed using mixed-methods with key informant semi-structured interviews that included 1) N=36 clinical providers from the 11 selected VHA sites (Table 1) where inpatient telestroke consults are initiated, including emergency medicine (EM) physicians, internal medicine (IM) hospitalists, neurologists, and nursing staff and 2) N=8 NTSP telestroke providers, including tele-neurologists, physician assistants (PAs), and nurse coordinators. Semi-structured interview guides were used along with Likert (scaled 1-7) ratings of acceptability. We analyzed interviews using Rapid Qualitative Analysis methods, with a matrix guided by the RE-AIM framework with extracted key concepts and themes related to the adoption, reach, effectiveness, and implementation. All interviews were discussed by team members to achieve consensus on identified concepts/themes.

Results:
Providers reported high acceptability of the subacute telestroke consult service (84.2% rated usefulness
≥
6/7). Key facilitators of the subacute telestroke service included: filling a critical need, on-site champions, and reduction in interhospital transfers. Ongoing barriers included: confusion between the acute/subacute services, site-level infrastructural barriers, and program awareness (Table 2). EM physicians (N=5) rated the usefulness of the service numerically higher than IM physicians/hospitalists (N=10; mean score 7 vs 6.3), a difference apparent in some interviews. Inpatient local neurology coverage led to unique implementation challenges, with historical practice patterns and differences of recommendations noted (Table 3). However, usefulness ratings were similar between sites with/without local neurology.

Discussion:
Implementing an inpatient subacute telestroke consult service filled a critical gap in stroke care within the VHA. Addressing confusion between acute/subacute telestroke consults, efforts to maintain site awareness, and sensitivity to working with local neurology may be helpful implementation strategies for subacute telestroke programs.
Abstract 150: Racial and Ethnic Disparities in Post-stroke Quality of Life: A Post-Hoc Analysis of the SHINE Trial
Authors: Littig Lauren , Calvario Erick , Wong Ka-Ho , Krothapalli Neeharika , Kim Yvonne , Smith Harper , de Havenon Adam
Published: January 2025

Background and Purpose:
Stroke is a leading cause of long-term disability, often resulting in functional and cognitive impairments that significantly reduce quality of life. While racial and ethnic differences in clinical outcomes after stroke are well-documented, the impact of post-stroke disability on patient-centered outcome measures, which account for physical, emotional, and sociocultural factors, remains insufficiently understood. This study aimed to investigate racial and ethnic differences in post-stroke quality of life among participants in the SHINE trial.

Methods:
This is a post-hoc analysis of the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial. Self-reported race, ethnicity, and the 12-item Stroke Specific Quality of Life (SSQOL) Scale at 90-day follow-up were used for correlation analyses, adjusted for age, sex, hypertension, diabetes, stroke size, recurrent stroke, and 90-day modified Rankin Scale. The SSQOL is a patient-centered outcome measure that assesses health-related quality of life specific to stroke survivors across 12 domains (Table 1).

Results:
A total of 907 ischemic stroke patients with hyperglycemia (mean age 65±12.8, 44.7% female, 80.9% with diabetes) were included in this study. At 90-day follow-up, no significant differences were found in overall SSQOL summary scores by race/ethnicity. However, Hispanic patients reported significantly lower scores in self-care (p < .0001) (Figure 1), vision (p = .015), and upper extremity function (p = .007), while Black patients reported lower energy (p = 0.012).

Discussion:
These findings indicate that Hispanic and Black stroke survivors experience lower quality of life in specific domains after adjusting for stroke severity and other potential confounders. In addition to clinical outcomes, it is crucial to understand stroke survivors’ perceptions of their quality of life which can inform more culturally competent care. Future research should validate these associations and examine the role of socio-economic factors in shaping post-stroke quality of life to promote effective and equitable care in line with the WHO 2030 Rehabilitation agenda.
Abstract 152: Bridging the Gap in Stroke Care: Enhancing Early Detection of Cognitive Impairments Through Standardized Screening Improves Therapy Referrals
Authors: Phillips Taylor , Vnenchak Leslie , Sloane Kelly
Published: January 2025

Cognitive and speech impairments are common after stroke, contributing to greater functional dependence and a diminished quality of life. Despite this, during acute stroke hospitalization, screening for these impairments using validated tools is rarely conducted beyond routine bedside examinations by medical providers.

This quality improvement project aimed to enhance the early detection of speech and cognitive impairments in stroke patients. We hypothesized that there would be low concordance between provider perceptions of cognitive impairments and objective measures and that the referral rate for outpatient speech therapy would increase following the intervention.

From 07/01/24 to 08/31/24, stroke patients were screened for cognitive and language function using Saint Louis University Mental Status (SLUMS) and Quick Aphasia Battery (QAB), respectively. Providers were also surveyed on their perceptions of the patients' cognitive and language impairments and their intent to refer them for outpatient rehabilitation.

Analysis revealed a significant association between QAB score and providers’ beliefs, χ
2
(2, N = 19) = 6.97, p = 0.031, suggesting that providers are more likely to recognize impairments as severity increases. Linear regression comparing provider scores and SLUMS scores showed R
2
= 0.13, indicating that provider ratings were unreliable. A significant difference was found in referral rates before and after the intervention compared to the same period in 2023, χ
2
(1, N = 77) = 4.52, p = 0.034.

These findings indicate that mild and moderate cognitive impairments are frequently overlooked in acute stroke care. The discrepancy between provider assessments and standardized screening highlights the inadequacy of current bedside evaluations. Moreover, the significant increase in referrals following the implementation of validated screenings supports the effectiveness of this approach in promoting timely intervention for stroke survivors.
Abstract 154: 10-Year Trend Analysis of Medicare Payment in Stroke Inpatient Hospital Admission
Authors: Wong Ka-Ho , Krothapalli Neeharika , Littig Lauren , Champagne Alison , Majersik Jennifer , Reddy Vivek , de Havenon Adam
Published: January 2025

Background:
The direct medical costs of stroke in the United States were $84.4 billion in 2012 and were projected to rise by 157% to $217.3 billion by 2030. However, the 10-year trend in inpatient stroke care costs under Medicare, as well as the Medicare payment variation across different states, has yet to be thoroughly investigated.

Methods:
This is a retrospective analysis of the 2013 to 2022 Medicare Inpatient Hospitals - by Provider and Service Data that provides inpatient hospital charges by Medicare Severity Diagnosis Related Group (DRG) in stroke admission (DRG: 61-66). Percentage change in stroke admission cost adjusted for healthcare inflation between 2013-14 to 2021-22 weighted for the number in each stroke DRG was included in the analysis.

Results:
Between 2013 and 2022, nationwide there were a total of 2,007,005 unique stroke-related inpatient hospital claims, resulting in Medicare payments totaling $21.07 billion from the Medicare Services. In 2013, the mean Medicare payment, weighted per stroke DRG for each stroke admission, was $9,486.08 (95% CI: $9,448.98–$9,523.18) nationwide. By 2022, after adjusting for healthcare inflation, the mean Medicare payment, weighted per stroke DRG, increased to $10,047.34 (95% CI: $9,994.39–$10,100.30) nationwide (Figure 1). At the state level, the 10-year analysis of Medicare payment for stroke admissions revealed a 33% decrease in payment costs in Vermont, while Maryland experienced the highest increase, with a 23% rise in Medicare payment costs (Figure 2).

Conclusion:
Nationwide, the overall Medicare payment for stroke-related DRG costs has increased by over $560 in the past decade after adjusting for healthcare inflation and weighted per-stroke DRGs. However, at the state level, certain states have experienced a reduction in Medicare payments for stroke admissions.
Abstract 156: A Mast Cell-Specific Receptor Mediates Post-Stroke Brain Inflammation Via a Dural-Brain Axis
Authors: Kothari Ruchita , Abdulrahim Mostafa , Oh Hyun Jong , Capuzzi Daniel , Nair Sumil , Zhang Yaowu , Limjunyawong Nathachit , Saini Sarbjit , Kim Jennifer , Caplan Justin , Gonzalez L. Fernando , Jackson Christopher , Bettegowda Chetan , Huang Judy , Koehler Raymond , Tamargo Rafael , Xu Risheng , DONG XINZHONG
Published: January 2025

Background:
Brain inflammation following ischemic stroke exacerbates neuronal injury. Early immune cell infiltration into the brain after ischemia is correlated with increased risk of subsequent stroke and higher three-month mortality. However, direct mechanisms that underly this immune cell recruitment remain unclear, preventing the development of successful therapeutics. Recent work has identified mast cells as early responders in stroke that incite inflammation, yet how these cells are activated remains unknown. We hypothesized that Mrgprb2, a mast cell receptor known to trigger neurogenic inflammation, initiates mast cell activity in stroke, and that inhibition of this receptor can attenuate stroke injury.

Methods:
We performed MCA occlusion (MCAO) on wild-type and Mrgprb2-null (Mrgprb2
-/-
) mice and assessed stroke volume, and behavior. We used flow cytometry and ELISA for immune cell and cytokine profiling to evaluate inflammation. Human stroke patient dura and blood was sampled to assess mast cell activity and to identify potential ligands for Mrgprb2 activation. Lastly, we used osthole, a Mrgprb2 inhibitor, as a post-MCAO treatment to determine if pharmacologic inhibition can attenuate post-stroke deficits in mice.

Results:
We found that Mrgprb2 is activated in meningeal mast cells after stroke, causing mast cell degranulation and release of chemokines that attract immune cells. Mrgprb2
-/-
mice exhibited reduced brain inflammation after stroke, leading to attenuated infarct size, and reduced mortality. Further, we show evidence that Mrgprb2
-/-
mice recruited fewer skull bone marrow neutrophils into the brain, suggesting a novel mechanism whereby mast cells regulate skull bone marrow recruitment. We demonstrated that the human ortholog of this receptor, MRGPRX2, is expressed in human meningeal mast cells, and that these cells are activated in stroke patients. Further, substance P, a known ligand of Mrgprb2/X2, is increased in stroke patient serum. Lastly, osthole-treated mice have reduced post-stroke brain inflammation and improved functional outcomes, confirming that pharmacologic inhibition of Mrgprb2 is a promising therapeutic strategy.

Conclusions:
Our study identifies Mrgprb2 as a key receptor which triggers mast cell activity in stroke and initiates brain inflammation. Mrgprb2/X2 provides a specific and druggable target to attenuate post-stroke inflammation and holds potential to meaningfully alter the clinical course for stroke patients.
Abstract 158: Post-Stroke Migrasome-dependent Lysosomal Quality Control Supports Microglia/macrophage Efferocytosis via TSPAN14
Authors: Hu Mengyan , Cai Wei , Lu Zhengqi
Published: January 2025

Introduction:
Clearing necrotic tissue from lesions by microglia/macrophage is crucial for recovery after acute ischemic stroke (AIS). Lysosomal activity is key for efferocytosis. In the chronic phase, reduced lysosomal activity impairs clearance, causing residual debris and worsening cognitive impairment. Migrasomes, formed during cellular migration, help maintain other organelles like mitochondria.

Hypothesis:
This study explored how migrasomes in microglia/macrophage help load damaged lysosomes for expulsion, preserving lysosomal quality and efferocytosis post-stroke.

Methods:
Male C57BL/6 mice including wild-type (WT) and
Tspan14
conditional knockout (

Tspan14
fl/fl
Lyz2
Cre

, TSPAN14 CKO) underwent transient middle cerebral artery occlusion (tMCAO). Migrasome production and TSPAN14 expression were evaluated through staining and nano flow cytometry. Neurobehavioral performance was measured by rotarod, foot fault, novel object recognition, and water maze tests up to 14 days post-stroke. In vitro, bone marrow-derived macrophages (BMDM) were cultured with blebbistatin to inhibit migrasome production. BMDM efferocytosis of dead neurons was assessed by staining and flow cytometry.

Results:
In cultures, 76.9% of migrasomes from BMDM engulfing dead neurons contained damaged lysosomes. Inhibiting migrasome production in BMDM impaired efferocytosis and increased damaged lysosome accumulation. TSPAN14 on the lysosomal membrane mediated lysosome sorting into migrasomes. Migrasomes from TSPAN14 CKO BMDM engulfing dead neurons had 62.3% less lysosomal content than those from WT BMDM, though their numbers were similar (
P
<0.05). BMDM from TSPAN14 CKO mice had 212.4% more damaged lysosomes and 54.7% less efferocytosis compared to WT BMDM (
P
<0.05). In tMCAO model, migrasome production and TSPAN14 expression increased in Iba1
+
microglia/macrophage after stroke, peaking on day 3 and stabilizing by day 7. By day 14, both decreased. TSPAN14 CKO mice had worse sensorimotor and spatial learning deficits than WT mice 14 days after tMCAO (
P
<0.05). Microglia/macrophage in TSPAN14 CKO lesions had more damaged lysosomes and reduced efferocytosis (
P
<0.01).

Conclusions:
TSPAN14 regulates lysosomal quality through migrasome-dependent mechanisms. In the chronic stroke phase, reduced TSPAN14 impairs lysosomal control in microglia/macrophage, leading to incomplete clearance and worsened cognitive impairment. Thus, TSPAN14 is a promising target to enhance clearance and improve stroke outcomes.
Abstract 159: Cerebral endothelial cells generate ceramides that worsen outcomes of acute ischemic stroke in mice.
Authors: Mookherjee Sohom , Wilson Jack , Maschek John , Proia Richard , Summers Scott , Holland William , Campbell Robert , Denorme Frederik , Symons J David
Published: January 2025

Acute ischemic stroke (AIS) elevates plasma ceramides that correlate with the prevalence and severity of neurological and motor deficits displayed by these patients. Our preclinical murine model of AIS [60-min transient middle cerebral artery occlusion (tMCAO) followed by 23-hr reperfusion (R)] increases ceramides (targeted mass spectrometry) in plasma and ipsilesional (ischemic) brain hemispheres compared to sham-operated controls. Notably, AIS-induced ceramides accumulated in cerebral endothelial cell (EC)-enriched but not non-EC (NEC)-enriched fractions (magnetic activated cell sorting). These findings inspired the hypothesis that preventing AIS-induced cerebral EC ceramide accrual mitigates infarct volume, neurological and motor deficits in mice. Dihydroceramide desaturase 1 (DES1, gene:
Degs1
) catalyzes toxic ceramide generation from inert dihydroceramide. We deployed a cerebral EC-specific adeno-associated virus BR1 serotype (AAV-BR1) to either carry Cre-recombinase (AAV-BR1-
Cre
) or Null virus (AAV-BR1-Null) to adult, male
Degs1
fl/fl
mice, enabling selective depletion of
Degs1
in cerebral ECs (aka Cre-Degs1) or not (Null-Degs1) [n=5 each]. Fourteen days after tMCAO+R,
Degs1
gene expression was reduced (p<0.05) in ECs (but not NECs) isolated from ipsilesional hemispheres of Cre-Degs1 vs. Null-Degs1 mice. Further, AIS-induced infarct volume (TTC staining), neurological (Bederson score) and motor (Grip score) deficits were less severe (all p<0.05) in Cre-Degs1 vs. Null-Degs1 mice, suggesting that loss of cerebral EC-specific ceramide generation improves AIS outcomes. To substantiate these findings, we used a gain of cerebral EC ceramide approach. Serine palmitoyl transferase (SPT), the committed enzyme in ceramide biosynthesis, is comprised of 3-subunits. We deployed AAV-BR1-
Cre
(or Null vector) to adult, male mice enabling overexpression of a fusion (f) construct comprising the 3 SPT subunits preceded by STOP
fl/fl
, enabling rapid synthesis of cerebral EC ceramides (aka Cre-fSPT mice) or not (aka Null-fSPT mice) [n=5 each]. Fourteen days after tMCAO+R, we confirmed that SPTLC1 and SPTLC2 gene expression was elevated (p<0.05) in ECs (but not NECs) of ipsilesional hemispheres of Cre-fSPT vs. Null-fSPT mice. Importantly, AIS-induced infarct volume, neurological and motor deficits were greater (all p<0.05) in Cre-fSPT vs. Null-fSPT mice. Cerebral EC ceramide accrual might represent a new therapeutic target to combat the debilitating complications of AIS.
Abstract 161: Cooling the Intestines Offers Superior Protection in the Mouse Stroke Model
Authors: Liu Chunli , Park Yujung , Olivas Garcia Yamileck , Villa Jose , Osterli Emily , Chen Yingxin , Hu Bingren
Published: January 2025

Background:
Intestinal immune response plays a detrimental role following a stroke. The objective of this study aims to investigate if cooling the gut can protect the brain against ischemic injury.

Methods:
Mice were subjected to 60 min middle cerebral artery occlusion (MCAO) followed by 7 days of reperfusion. The experimental groups were: (i) normothermic group (NT) (n=11); (ii) colon cooling (CC) group (n=13); and (iii) surface cooling (SC) group (n=15). A temperature management catheter was inserted via the rectum into the descending colon to maintain the colon temperature at 37°C (NT group) and at 15°C (CC group), while the esophageal temperature was kept as close to 37°C as possible for both groups. In the SC group, both esophageal and colon temperatures were maintained at the same level as the esophageal temperature in the CC group. Temperature management was initiated at 30 min reperfusion and continued for 3 hours. The regional cerebral blood flow (rCBF) was measured during the peri-MCAO period. Bodyweight, behavioral deficits (nesting, pole test, and Y-maze), and neurological scores were examined daily until the 7-day endpoint. At the endpoint, mice were perfusion-fixed for histopathological analysis.

Results:
The rCBF was reduced below 10% of the preischemic level during the entire 60 min MCAO period. It returned to the preischemic level at 10 min post-MCAO but gradually declined to 50% of the preischemic level in CC and SC groups and to 70% in NT group by the end of temperature management. Stroke volume was the smallest in CC, smaller in SC, but the largest in NT group. Bodyweight continuously declined in SC and NT but recovered in CC group post-MCAO. Nest building activity and pole test deficits improved in CC but remained in NT or SC group. Neurological score deficits were recovered in CC, partially recovered in SC, but not recovered in NT group. The mortality rate was the lowest in CC, lower in SC, and the highest in NT group. Stroke volumes and behavioral deficits were significantly reduced in the CC compared to the NT group (p<0.01). Post-MCAO SC tended to reduce stroke injury compared to post-MCAO NT, although this reduction did not reach statistical significance.

Conclusion:
Post-MCAO intestinal cooling-induced hypothermia offered enhanced brain protection against stroke, which is superior to that offered by the systemic body surface cooling-induced hypothermia.
Abstract 3: Methylprednisolone as Adjunct to Thrombectomy in Acute Ischemic Stroke with Intracranial Internal Carotid Artery Occlusion: A secondary analysis of the MARVEL randomized trial
Authors: Zheng Chong , Shen Chaoxiong , Hu Zhizhou , Li Rongtong , Guo Fang , Fan Daofeng
Published: January 2025

Importance:
Acute ischemic stroke patients due to intracranial internal carotid artery (ICA) occlusion often have poor functional outcomes despite endovascular treatment (EVT).

Objective:
To investigate the efficacy and safety of intravenous methylprednisolone as adjunct treatment to EVT for patients with intracranial ICA occlusion.

Design, Setting, and Participants:
This was a post-hoc analysis of the MARVEL randomized, double blind, placebo-controlled clinical trial conducted from February 2022 to June 2023 at 82 stroke centers across China. The primary trial enrolled 1680 patients with large vessel occlusion within 24 hours from last known well time in the intracranial ICA, M1 or M2 middle cerebral artery segments, of whom 579 patients had intracranial ICA occlusion. Data were analyzed in April 2024.

Intervention:
Patients were randomly assigned to intravenous methylprednisolone at 2 mg/kg/d (maximum dose of 160 mg) for 3 days plus EVT versus placebo plus EVT.

Main outcomes and measures:
The primary outcome was independent ambulation at 90 days defined as a score of 0-3 on the modified Rankin Scale (range from 0 [no symptoms] to 6 [death]). Safety outcomes included death within 90 days, symptomatic intracranial hemorrhage (sICH) within 48 hours and decompressive hemicraniectomy to relieve midline-shift and intracranial pressure after EVT.

Results:
Among 579 patients (median age 69 years; 41.6% female), there were 286 and 293 patients in the methylprednisolone and placebo group, respectively. The proportion of patients who achieved 90-day independent ambulation was significantly higher in the methylprednisolone group than in the placebo group (53.2% vs 42.7%; adjusted OR, 1.46, 95% CI 1.16 to 1.84,
P
=0.001). The incidence of sICH was lower in the methylprednisolone than the placebo group (9.4% vs. 15.5%, adjusted RR, 0.6, 95% CI 0.38 to 0.94，
P
=0.026). The rate of decompressive hemicraniectomy was lower in the methylprednisolone compared to the placebo group (5.6% vs 9.9%; adjusted RR, 0.54 [95% CI, 0.30-0.98];
P
=0.044). No significant difference was observed in mortality between groups.

Conclusion and relevance:
Intravenous methylprednisolone was associated with improved ambulation, reduced symptomatic intracranial hemorrhage and decompressive hemicraniectomy in patients with acute ischemic stroke secondary to intracranial ICA occlusion undergoing EVT within 24 hours of last known well.
Abstract 37: Long-Term Results of Bypass Surgery for Symptomatic Carotid and Middle Cerebral Artery Occlusion (CMOSS-FU)
Authors: Ma Yan , Wang Tao , Ni Wei , Wang Haibo , Liu Delin , Sun Xinyi , Tong Xiaoguang , Zhang Liyong , Zhiyong Tong , Wang Yufeng , CAI YILING , Jun Ren , Donghai Wang , Duan Lian , Aisha Maimaitili , Chunhua Hang , Yu Jiasheng , Ling Feng , Wu Yangfeng , Derdeyn Colin , Gu Yuxiang , Zhao Guoguang , Jiao Liqun
Published: January 2025

Background:
In the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS), we found no significant difference between the bypass surgery group and the medical group with respect to the primary composite outcome of stroke or death within 30 days or any subsequent ipsilateral ischemic stroke within 2 years of follow-up. We now extend the long-term follow-ups to 10 years.

Methods:
We randomly assigned symptomatic patients with hemodynamically compromised internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion to extracranial-intracranial (EC-IC) bypass surgery plus medical treatment or medical treatment alone at 13 centers in China. We extended the follow-ups from the original 2 years to 10 years to assess long-term outcomes. The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days after randomization.

Results:
324 patients were assigned to the surgery (n=161) or medical group (n=163); the median duration of follow-up was 7.6 years (interquartile range [IQR], 2.3 to 9.2). The primary outcome occurred in 18 of 161 patients (11.2%) in the surgical group, significantly lower than that in the medical group (32 out of 163 patients [19.6%]; relative risk [RR], 0.57; 95% confidence interval [CI], 0.33 to 0.97; P=0.04). The risk of any stroke was 16.1% in the surgical group vs 23.3% in the medical group (RR, 0.76; 95% CI, 0.52 to1.13; P=0.15); the all-cause mortality was 8.1% in the surgical group vs. 8.6% in the medical group (RR, 0.94; 95% CI, 0.46 to 1.94]; P=0.93).

Conclusions:
Among symptomatic ICA or MCA occlusion patients with hemodynamic insufficiency, the addition of extracranial-intracranial bypass surgery to medical treatment was safe and led to a lower risk of recurrent stroke through 7 years of follow-up than medical treatment alone. (ClinicalTrials.gov number, NCT01758614.)
Abstract 48: Effect of Remote Ischemic Conditioning on Functional Outcomes in Patients With Supratentorial Intracerebral Hemorrhage: The Final Results of RICH-2 Randomized Controlled Clinical Trial
Authors: Wenbo Zhao , Wu Chuanjie , Song Haiqing , Duan Jiangang , Ma Qingfeng , Li Sijie , Ji Xunming
Published: January 2025

Introduction:
Supratentorial intracerebral hemorrhage (ICH) is a devastating stroke subtype with high mortality and morbidity, and hematoma clearance is a critical therapeutic target. Remote ischemic conditioning (RIC) with transient ischemia and reperfusion applied to the arm has been shown to accelerate hematoma resolution in both animal and clinical studies. The RICH-2 trial investigated whether RIC could improve the functional outcomes of patients with ICH.

Methods:
In this investigator-initiated, multicentre, prospective, randomized, sham-controlled, outcome-blinded parallel-group trial conducted in 20 centers in China, patients (age 18 to 80 years) with supratentorial ICH presenting within 24-48 h of ictus who do not need surgical therapy were randomly allocated (1:1, stratified by baseline NIHSS and clot size) to receive RIC or sham RIC for 7 consecutive days after randomization in addition to best medical management. The primary outcome was a score of 0-2 on the modified Rankin Scale at 90 days, analyzed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04657133.

Results:
Between Apr 22, 2021, and Oct 30, 2023, 458 patients were randomly assigned, with 229 in each group. 134 (29.3%) were women, and 324 (70.7%) were men, the median age was 58 years (IQR 51-68), the median NIHSS score was 9.0 (IQR 7.0-13.0), and the median hematoma volume was 12.6 mL (IQR 10.0-18.0). 156 (68.1%) of 229 patients in the RIC group and 163 (71.2%) of 229 patients in the sham group had a mRS score of 0-2 at 90 days (adjusted RR 0.98; 95% CI 0.88-1.09; adjusted p=0.69). Prespecified subgroup analysis showed a trend in favor of RIC in patients with clot size larger than 20 ml (RR 1.26, 95% CI 0.80-1.98, p=0.31). At 180-day follow-up, 169 (73.8%) of 229 patients receiving RIC and 175 (76.4%) of 229 patients receiving sham RIC achieved a mRS score of 0-2 (adjusted RR 0.98; 95% CI 0.89-1.08; adjusted p=0.64). Serious adverse events occurred in 16 (7.0%) of 229 patients receiving RIC and 12 (5.2%) of 229 patients receiving sham RIC (adjusted RR 1.29, 95% CI, 0.63-2.67, p=0.48). No important unexpected adverse events or side effects of RIC were observed.

Conclusions:
RIC did not improve the proportion of patients who achieved functional independence 90 days after ICH in patients who did not need surgical therapy. Further studies of RIC in this population should target patients with large clot sizes and address the RIC protocol.
Abstract 5: Glyburide for Large Hemispheric Infarcts ≤125 mL: a Meta-Analysis of Individual Patient Data from the GAMES-RP and CHARM Trials
Authors: Kimberly W Taylor , Hinson H.E. , Albers Greg , Saver Jeffrey , Campbell Bruce , Molyneaux Bradley , Cordonnier Charlotte , Steiner Thorsten , Toyoda Kazunori , Wintermark Max , Nogueira Raul , Simard J Marc , Jacobson Sven , Sheth Kevin
Published: January 2025

Introduction:
Two randomized trials have evaluated intravenous (IV) Glyburide for the treatment of large hemispheric infarction (LHI) patients at high risk for cerebral edema.

Hypothesis:
In this meta-analysis of two randomized trials, we aimed to determine whether subjects with a baseline stroke volume ≤125 mL who were treated with IV Glyburide would have better outcomes than those who received placebo.

Methods:
The source population included all GAMES-RP and CHARM subjects who were enrolled and treated with IV Glyburide or placebo, were ≤70 years of age, and had a baseline stroke volume ≤125 mL (n=138). The outcome of interest was the modified Rankin Scale (mRS) score at 90 days using 5 categories, where 0-1 and 5-6 were each collapsed into a single category. We used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in the subgroup with a baseline stroke volume ≤125 mL after adjustment for age, sex, baseline NIHSS, region of world, image modality, thrombolysis and thrombectomy (yes versus no).

Results:
The cohort included a total of 138 subjects with a mean age 58±10 years, 34% female, baseline NIHSS 18 (15-21), 46% received thrombolysis, baseline stroke volume 97 ml (84-108). The median 90-day mRS was 3 (2-4). Among these patients at 90 days, IV Glyburide was associated with better functional outcome (cOR 2.56, 95% CI 1.28-5.11, p=0.008).

Conclusions:
Individual patient data meta-analysis of 138 subjects enrolled in the GAMES-RP and CHARM trials show that IV Glyburide was associated with an improvement in functional outcome compared to placebo when the baseline stroke volume was ≤125 mL. This finding requires confirmation in a future clinical trial.
Abstract 50: Co-localization of NCCT hypodensity and CTA spot sign to predict intracerebral hematoma expansion and severity: development and validation of the Black,-&-White sign
Authors: Pensato Umberto , Tanaka Koji , Horn MacKenzie , Teleg Ericka , Al Sultan Abdulaziz , Kasickova Machova Linda , Ohara Tomoyuki , Ojha Piyush , Marzoughi Sina , Banerjee Ankur , Kulkarni Girish , Menon Bijoy , Goyal Mayank , Hill Michael , Molina Carlos , Silva Yolanda , boulanger jean-martin , Gubitz Gord , Bhatia Rohit , SRIVASTAVA PADMA , Roy Jayanta , Dzialowski Imanuel , Kase Carlos , Kobayashi Adam , Rodriguez-Luna David , Aviv Richard , Dowlatshahi Dar , Demchuk Andrew
Published: January 2025

Introduction:
Hematoma expansion (HE) occurs in one-fourth of patients with acute intracerebral hematoma (ICH) and is associated with worse outcomes. Existing radiological markers of HE show modest predictive accuracy. We aim to investigate a novel radiological marker that co-localizes findings from non-contrast CT (NCCT) and CT angiography (CTA) to predict HE.

Methods:
We analyzed 200 consecutive acute ICH patients admitted at Foothills Medical Centre in Calgary, Canada (development cohort) and analyzed 304 patients from the multicenter observational study PREDICT (validation cohort). The Black-&-White (B&W) sign was defined as any visually identified spot sign on CTA co-localized with a hypodensity sign on the corresponding NCCT (
Figure 1
). The primary outcome was hematoma expansion (≥6mL or ≥33%). Secondary outcomes included absolute (<3mL, 3-6mL, 6-12mL, ≥12mL) and relative (0%, <25%, 25-50%, 50-75%, or >75%) hematoma growth scales.

Results:
In the development cohort, 22% (n=44) showed the spot sign, 34.5% (n=69) the hypodensity sign, and 7% (n=14) the B&W sign. Those with the B&W sign had higher proportions of HE (100% vs. 19.4%, p<0.001), greater absolute hematoma growth (23.37 mL [IQR=15.41-30.27] vs. 0 mL [IQR=0-2.39], p<0.001) and relative hematoma growth (120% [IQR=49-192] vs. 0% [0-15%], p<0.001) in comparison to those without. The B&W sign yielded a specificity of 100%, a PPV of 100%, and an accuracy of 82%.

In the validation cohort, 25% (n=76) showed the spot sign, 39.1% (n=119) the hypodensity sign, and 9.5% (n=29) the B&W sign. Those with B&W signs had higher proportions of HE (79.3% vs. 30.2%, p<0.001), greater absolute hematoma growth (19.1 mL [IQR=6.4-40] vs. 0.8 mL [0-5.6], p<0.001), and relative hematoma growth (92% [IQR=16-151%] vs. 9% [0-34%], p<0.001) in comparison to those without. The B&W sign yielded a specificity of 97%, a PPV of 79%, and an accuracy of 71%. We found a consistent progressive improvement in predicting HE when hypodensity and spot signs are absent, individually present, both present but not co-localized, and co-localized (
Figures 2-3
). The inter-rater agreement was excellent (k=0.84) in the development cohort, with a uniform imaging protocol of NCCT immediately followed by CTA at a single center, and moderate (k=0.54) in the validation cohort at multiple centers.

Conclusion:
The Black-&-White sign is a robust predictor of hematoma expansion occurrence and hematoma expansion severity.
Abstract 51: Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Prevention of Stroke among Patients with Type 2 Diabetes Mellitus, Heart Failure, or Obesity: A Meta-Analysis of 12 Randomized Controlled Trials.
Authors: Jaiswal Vikash , Jaiswal Akash , Borra Vamsikalyan , Latif Fakhar , Gera Asmita , Ang Song Peng , Kalra Kriti , Danisha FNU , Mashkoor Yusra , Mattumpuram Jishanth , Biswas Monodeep
Published: January 2025

Background:
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). However, its efficacy on cerebrovascular events is yet to be well established, with conflicting results to date.

Objective:
We sought to evaluate the efficacy of GLP-1 RAs on stroke risk among its different types in patients with T2DM, heart failure, or obesity.

Methods:
We performed a systematic literature search on PubMed, EMBASE, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) from inspection until June 30th, 2024, without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model, and a p-value of <0.05 was considered statistically significant.

Results:
A total of 12 RCTs with 85,673 patients (43,493 in GLP-1 RAs and 42,180 in the placebo group) were included in the analysis. The mean age of the patients in GLP-1 RAs and the placebo groups was 63.5 and 63.1 years, respectively. Pooled analysis of primary and secondary endpoints showed that GLP-1 RAs significantly reduced the risk of incidence of stroke by 12% (OR, 0.88(95%CI: 0.81-0.96),
P
<0.001), and nonfatal stroke by 13% (OR, 0.87(95%CI: 0.79-0.95),
P
<0.001) compared with placebo. However, the risk of fatal stroke (OR, 0.94(95%CI: 0.75-1.17),
P
=0.56) was comparable between both groups of patients. Similarly, the risk of serious adverse events such as cerebrovascular accident (OR, 0.75(95%CI: 0.57-1.00),
P
=0.05), hemorrhagic stroke (OR, 0.82(95%CI: 0.42-1.60),
P
=0.57, and ischemic stroke (OR, 0.85(95%CI: 0.64-1.13),
P
=0.26) was comparable between GLP-1RAs and placebo.

Conclusion:
GLP-1 RAs therapy was associated with an overall reduction in the risk of stroke and nonfatal stroke in T2DM and/or heart failure or obese patients. However, no such effect was observed for fatal stroke.
Abstract 52: Glucagon-like peptide-1 receptor agonists use and outcomes in Cardiac Amyloidosis patients: A Propensity Matched Analysis
Authors: Jaiswal Vikash , Hanif Muhammad , Kalra Kriti , Mashkoor Yusra , Jaiswal Akash
Published: January 2025

Background:
Despite their potential, Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have not been well studied in cardiac amyloidosis (CA) as randomized trials on GLP-1 RA have excluded patients with this morbid disease.

Objective:
This study aims to investigate the association of GLP-1 RA with outcomes in patients with Cardiac Amyloidosis.

Method:
The TriNeTX Global Collaborative Network research database was used to identify patients aged ≥18 years of age from January 2005 to August 2023. Patients were categorized into two groups, one with cardiac amyloidosis on GLP-1 RA and a control group with cardiac amyloidosis without GLP-1 RA. Patients were assessed at follow-up periods of 1 month and 1 year. Propensity score-matched analysis (PSM) (1:1) was performed with matching for age, gender, race, BMI, hypertension, diabetes mellitus, chronic kidney disease, hemoglobin level, low-density lipid (LDL) level, left ventricular ejection fraction, and various drugs including ACEi, ARBi, ARNI, beta-blockers, and diuretics. Primary outcome was risk of ischemic stroke while secondary outcomes were all-cause mortality (ACM), heart failure, acute myocardial infarction (AMI), major adverse cardiovascular events (MACE), atrial fibrillation (AF), and ventricular tachycardia (VT).

Result:
After 1:1 propensity score matching, the study cohort comprised 895 patients receiving GLP-1 RA and 895 patients in the control group. The study population had a mean age of 68± 0.14 years, with 49.27% men. PSM analysis showed that GLP-1 RA did not reduce the risk of ischemic stroke after 1 month (RR, 1.00(95%CI: 0.42-2.39), P=0.99). However, GLP-1 RA significantly reduced the risk of ischemic stroke after 1 year (RR, 0.43(95%CI: 0.25-0.73), P<0.01). A significant reduction in the risk of ACM after 1 month (RR, 0.28(95%CI: 0.14-0.56), P<0.01), and after 1 year (RR, 0.32(95%CI: 0.23-0.45), P<0.01) was observed. Similarly, a significant reduction in the risk of MACE after 1 year (RR, 0.28(95:CI: 0.17-0.46), P<0.01), AMI after 1 year (RR, 0.55(95%CI: 0.35-0.88), P=0.01), and AF after 1 year (RR, 0.58(95%CI: 0.36-0.94), P=0.01) was observed among GLP-1 RA group patients. Risk of Heart failure and VT was comparable.

Conclusion:
These findings indicated that GLP-1 RA are associated with a reduction in the risk of ischemic stroke, all cause mortality, MACE, and atrial fibrillation among cardiac amyloidosis patients, without increasing the risk of heart failure, or ventricular tachycardia.
Abstract 55: A Novel Thrombolytic with Anti-inflammatory Properties (JX10) Improves Neurological Outcomes in Acute Lacunar Infarct up to 12 hours After Onset
Authors: Chen Edmond , Niizuma Kuniyasu , Nitika Fnu , Hasumi Keiji , Tominaga Teiji , Nishimura Naoko , Zhang Shenglin
Published: January 2025

Introduction:
Approved thrombolytic agents are currently only recommended for acute ischemic stroke (AIS) within 4.5 hours from the last known well (LKW). Hence, there remains an unmet need in the treatment of AIS for safer and more effective thrombolytics, which can also be administered to a broader population with an extended treatment window. JX10 is a novel thrombolytic that works by inducing conformational changes in plasminogen to increase downstream fibrin affinity and promote physiological fibrinolysis instead of direct plasminogen activation like that of tissue plasminogen activators (t-PA). JX10 also exerts anti-inflammatory activity through inhibition of soluble epoxide hydrolase, which may suppress hemorrhagic changes associated with cerebral infarction. In a randomized, double-blind, placebo-controlled, dose-escalation phase 2a study conducted in Japan, JX10 increased vessel recanalization and improved neurologic outcomes. This subgroup analysis evaluated the safety and efficacy of JX10 in participants who presented with acute lacunar infarct.

Methods:
JX10 or placebo was administered as a single intravenous infusion at a dose of 1, 3, or 6 mg/kg to AIS patients who were ineligible for tissue plasminogen activator or thrombectomy within 12 h of LKW. Safety and Efficacy outcomes were assessed at 90 days.

Results:
Among the 90 patients enrolled in the trial, a total of 25 patients with acute lacunar infarct were dosed (JX10 1 mg/kg group: 1 subject; 3 mg/kg group: 3 subjects; 6 mg/kg group: 7 subjects; and placebo group: 14 subjects). In the JX10 1, 3, 6 mg/kg, pooled groups, and the placebo group, the rates of mRS 0–1 were 0 subject out of 1 (0.0%), 1 subject out of 3 (33.3%), 3 subjects out of 7 (42.9%), 4 subjects out of 11 (36.4%), and 1 subject out of 14 (7.1%), respectively, and those of mRS 0–2 were 0 subjects out of 1 (0.0%), 3 subjects out of 3 (100.0%), 4 subject out of 7 (57.1%), 7 subjects out of 11 (63.6%), and 2 subjects out of 14 (14.3%), respectively. Despite small numbers, patients with acute lacunar infarct who were treated with JX10 showed trend of improved neurologic function at 90 days, as measured by mRS. Symptomatic intracranial hemorrhage was not observed in any JX10 treated patients.

Conclusions:
JX10 improved functional outcome in patients who presented with lacunar infarct, as measured by mRS at day 90 vs placebo. Findings support further testing of JX10 in larger and broader patient populations.