bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 106: Circulating Interleukin-6 Levels Early During Active Stroke Estimate Time of Stroke Onset: Potential New Clinical Biomarker Tool From a Mobile Stroke Unit
Authors: Kowalski Robert G , Ledreux Aurelie , Violette John , Neumann Robert , Grotta James C , Ornelas David , Thompson John A , Monte Andrew , Dylla Layne , Coughlan Christina , Yu Xiaoli , Graner Michael , Jones William
Published: February 2024

Background:
Circulating interleukin-6 (IL-6) concentrations are elevated in acute stroke but the timing of the IL-6 response in humans is unknown. We used a mobile stroke unit (MSU) to identify IL-6 levels within minutes of symptom onset. The results suggest a tool for estimating onset time for nearly 200,000 stroke patients annually in the U.S. in whom this is unknown.

Methods:
The study is a prospective, cohort investigation of ultra-early blood-derived IL-6 in acute stroke. Blood was obtained on the MSU, at 24 hours, and from hospital stroke patients and healthy controls. Plasma IL-6 was analyzed with ELISA. Confirmed strokes, mimics and controls were compared. Variables included demographics, DWI lesion volume, mRS, and NIHSS.

Results:
Forty-two adults were analyzed, including 28 patients treated on the MSU between August 2021 and May 2023, and 14 controls. Nineteen (68%) MSU patients were diagnosed as stroke, with 17 (61%) confirmed and 2 likely TIA or stroke averted by thrombolysis; 9 were stroke mimics. For confirmed stroke patients, median age was 72 (range 36-87) years, 47% were female, and 82% white. Median initial NIHSS score was 7 (range 1-22) and 12 (71%) received intravenous thrombolysis with tPA or TNK. Blood was obtained a median of 57 (range 26-158) minutes after symptom onset. IL-6 was elevated in all 17 confirmed stroke patients, a median of 3 times normal, as early as 26 minutes after symptom onset (median 6.4 pg/mL). In 15 (88%) cases, IL-6 increased over 24 hours, (median Δ 8.9 pg/mL). For mimics and healthy controls, median IL-6 was 5.9 and 2.3 pg/mL, respectively. Initial IL-6 in strokes was not associated with lesion volume (Spearman’s r= -0.035, p=894) or initial NIHSS (Spearman’s r=-0.043, p=869). Based on IL-6 trajectories observed, a cutoff for IL-6 set at 8 pg/mL had a sensitivity of 79% and specificity of 36% for estimating the stroke onset time was in the 4.5-hour thrombolysis window.

Conclusions:
This study found IL-6 was elevated in all confirmed strokes and increased in a linear fashion during the first 2.5 hours. IL-6 was independent of lesion volume and NIHSS. This suggests a rapid measurement of IL-6 from blood early in acute stroke may estimate onset time. The findings may aid development of immunomodulatory therapies for IL-6 in acute stroke.
Abstract 109: Towards Individualised Prediction of Neurodevelopmental Outcomes After Neonatal Stroke: A Brain Lesion Network Mapping Study Leveraging Large-Scale Datasets
Authors: Kelly Claire , Chen Jian , Beare Richard , Stojanovski Belinda , Grunt Sebastian , Slavova Nedelina , Pastore-Wapp Manuela , Steinlin Maja I , Mackay Mark T , Yang Joseph
Published: February 2024

Introduction:
Prediction of adverse neurodevelopmental outcomes after neonatal arterial ischemic stroke (NAIS) is challenging. We identified brain regions functionally connected to stroke lesions (lesion networks), and investigated whether such lesion networks are related to the development of cerebral palsy (CP) after NAIS.

Methods:
We performed a novel lesion network mapping approach, involving: 1. Creation of a normative connectome using the developing Human Connectome Project (dHCP) dataset. Resting state functional magnetic resonance imaging (MRI) scans of 518 neonates born at term (>36 weeks) from the dHCP were aligned to a template, built from
T
2
-weighted scans of the same neonates; 2. Manual segmentation of lesions using diffusion MRI scans of 85 term-born neonates with NAIS, who were identified from Australian and Swiss pediatric stroke registries. Lesion masks were aligned to the template; 3. Construction of lesion network maps, by computing functional correlations between lesion masks and other brain grey matter regions, making use of the normative connectome; 4. Investigation of relationships between lesion networks and CP, diagnosed by clinical examination at least 18 months after NAIS. Lesion network maps were compared between those who did (n=28) and did not (n=57) develop CP after NAIS, with two sample t-tests.

Results:
In participants who developed CP after NAIS, lesions were more strongly functionally connected to the following regions: frontal (inferior and orbital frontal), temporal (pole, superior, and mesial temporal), insula, basal ganglia, thalamus and cerebellum (Figure 1).

Conclusions:
Leveraging large-scale datasets and innovative connectomic methods, we uncovered brain networks related to adverse outcomes after NAIS. This provided novel findings compared to past methods such as voxel-based lesion-symptom mapping. Our results point to differences in network vulnerabilities after stroke in neonates compared to adults.
Abstract 111: Membrane Lipid-Sensing Receptor MS4A Modulates Microglial Reparative Phenotype in Acute Germinal Matrix Hemorrhage-Intraventricular Hemorrhage (GMH-IVH)
Authors: Chen Wen-Jung , Lin Tze-Yen , Hsu Chia-Lang , Chang Che-Feng
Published: February 2024

Background:
GMH-IVH refers to spontaneous bleeding in the periventricular germinal zone and ventricles of an immature brain. Preterm infants with GMH-IVH often have lifelong neurologic deficits. Microglia play crucial roles during development; however, what role they play in neonatal cerebrovascular injury such as GMH-IVH is less known. Here we established a mouse GMH-IVH model and unveiled an immature brain-specific microglial response.

Methods:
GMH-IVH and adult intracerebral hemorrhage (ICH)-IVH were induced by blood injection into the caudate-putamen and periventricular region of postnatal day 5 and 8-week-old mice. Astrogliosis, myelin loss, MS4A receptor expression, neuron morphology, and spine density were evaluated by immunofluorescence and Golgi’s staining. Transcriptome of microglia was profiled by NanoString. Cx3cr1
CreER
; iDRT mice and PLX3397 treatment were used to deplete microglia. Cognitive and affective functions were evaluated.
In vivo
siRNA delivery was used to explore the mechanism underlying acute microglia reparative activation after GMH-IVH.

Result:
Astrogliosis and myelin loss were sustained till at least 8 weeks after GMH-IVH. Reduced neuronal dendritic complexity in the dentate gyrus and medial prefrontal cortex suggested compromised neuronal development in GMH-IVH. Upon adulthood, GMH-IVH mice had impaired cognitive and affective functions . Microglia showed heterogeneous phenotypes on day 3 after GMH-IVH. Interestingly, acute depletion of microglia aggravated myelin loss and neurobehavioral deficits, implying a beneficial role of these cells in the early stage of GMH-IVH. Compared with day 28 after GMH-IVH and day 3 after ICH-IVH, microglia at day 3 GMH-IVH uniquely upregulated lipid-sensing receptor MS4A. Inhibition of MS4A worsened long-term GMH-IVH outcomes.

Conclusion:
MS4A-expressing microglia are beneficial for GMH-IVH and targeting their responses could be a therapeutic approach for treating GMH-IVH.
Abstract 116: Increased Collagen I/Collagen III Ratio is Associated With Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse
Authors: Shabani nabikandi Zahra , Schurger Joana , Yadav Alka , Liang Rich , Press Kelly , Weinsheimer Shantel , Schmidt Annika , Kim Helen , Su Hua
Published: February 2024

Background and purpose:
Brain arteriovenous malformation (bAVM) is an important risk factor for hemorrhagic stroke in young adults, but the underlying mechanisms are unclear. Increase of Col I/Col III ratio enhances vessel wall stiffness and renders vessel less resistant to changes of blood flow and pressure.

Hypothesis:
Col I/Col III ratio is increased in bAVM vessels, which is associated with bAVM hemorrhage.

Method:
Human bAVMs were collected from HHT and sporadic bAVM patients. Temporal lobe specimens from epilepsy patients were used as controls. Three mouse models were used: 1) PdgfbicreER;
Alk1
f/f
; 2) PdgfbicreER;
Eng
f/f
; 3)
Alk
1
f/f
. Mice in models 1 and 2 have
Pdgfb
promoter driving, tamoxifen (TM) inducible cre expression in endothelial cells (ECs). BAVMs were induced by intra-brain injection of AAV-VEGF to induce angiogenesis and i.p. injection of TM to delete
Alk1
or
Eng
in ECs. In model 3, bAVMs were by intra-brain injection of AAV-VEGF and an adenoviral vector expressing Cre to delete
Alk1
gene focally. Colony stimulating factor receptor inhibitor (PLX5622) was given to
Alk1
f/f
mice 8 week after model induction when bAVMs have fully developed to transiently deplete microglia. Vascular Col I and Col III levels were analyzed by immunostaining using anti- CD31 and anti-Col I or Col II antibodies. Brain AVM bleeding was detected by Prussian blue staining, and RNA-Sequencing used to study gene profiles.

Results:
Col I and Col III levels and the Col I/Col III ratio were higher in the vessels of human HHT and sporadic bAVM than controls. Col I/Col III ratio was higher in ruptured than unruptured sporadic bAVM. RNA-seq data shown that Col I and Co III mRNA levels were higher in
Eng
deficient bAVMs than normal brain angiogenic regions. Col I and Col III levels were higher on
Alk1
and
Eng
deficient bAVMs compared to normal vessels. Col I/Col III ratio was also increased in the
Alk1
deficient bAVMs. Depletion of microglia by PLX5622 reduced Col I and Col III levels and reduced microhemorrhage of
Alk1
deficient bAVMs.

Conclusion:
Col I, Col III and Col I/Col III ratio are increased on human and mouse bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I and Col III and hemorrhage in bAVMs in mice.
Abstract 121: Improvements in Cardiovascular Fitness Following Forced-Rate Aerobic Cycling in Individuals With Chronic Stroke
Authors: Linder Susan , Bischof-Bockbrader Andrea , Persson Daniel , Roberts Julie , Marino Alexandra , Li Yadi , Davidson Sara , Singh Tamanna , Lapin Brittany , Lee John , Bethoux Francois , Alberts Jay
Published: February 2024

Introduction:
Declines in cardiovascular function in individuals following stroke result in increased energy costs of movement, restrictions in participation, and increased risk for recurrent stroke and other cardiovascular diseases. We have developed a rehabilitation model that incorporates aerobic exercise training to harness its potential neuroplastic effects. Our aim is to identify the cardiovascular benefits from a forced-rate aerobic exercise (FE) intervention among individuals with chronic stroke compared to an upper extremity repetitive task practice (UE RTP) control group.

Hypothesis:
We hypothesized that FE would elicit greater improvements in cardiovascular fitness compared to the UE RTP intervention.

Methods:
A randomized clinical trial was conducted in which participants (N=60) completed 24 sessions over 8 weeks of FE followed by RTP (FE+RTP) or time-matched RTP alone. The FE+RTP group exercised at 60-80% of heart rate reserve on a motorized stationary semi-recumbent cycle ergometer for 45 minutes followed by 45 minutes of RTP. The control group completed 90 minutes of RTP. Metabolic exercise stress tests were conducted at baseline and post-intervention. Outcomes included peak oxygen consumption (peak VO2) and anaerobic threshold (AT).

Results:
Fifty participants completed the study intervention and pre/post stress tests. The FE+RTP group demonstrated significantly greater improvements in peak VO2 from 16.4±5.7 to 18.3±6.4 mL/min/kg compared to the RTP group (17.0±5.6 to 17.2±5.6 mL/min/kg, p=0.020) and significantly greater improvements in AT from 10.3±2.8 to 11.5±3.6 mL/min/kg compared to the RTP group (10.8±3.9 to 10.4±3.2 mL/min/kg, p=0.020).

Conclusions:
An aerobic exercise intervention integrated into rehabilitation was effective in eliciting significant and meaningful improvements in cardiovascular fitness. This novel rehabilitation model may be an effective approach to improve motor and cardiovascular function.
Abstract 122: Associations of BDNF, PATJ and LOC105372028 Polymorphisms With Functional Outcomes in Probable LVO
Authors: Dalberg Njall , Aldridge Chad , Sunmonu N Abimbola A , Braun Robynne , Cole John W , de Havenon Adam H , Heitsch Laura , Lohse Keith , Worrall Bradford B , Cramer Steven C , Jern Christina , Maguire Jane ,   GISCOME investigators, Lindgren Arne
Published: February 2024

Background:
Several studies have investigated the association between the BDNF, PATJ, and LOC105372028 genes and functional outcome after ischemic stroke. Large vessel occlusion (LVO) is a distinct ischemic stroke presentation with a large impact on clinical function, thus these variants warrant investigation in this important subpopulation.

Objective:
To investigate whether single nucleotide polymorphisms (SNPs) in the BDNF (rs6265), PATJ (rs76221407), and LOC105372028 (rs1842681) loci are associated with functional outcome after LVO ischemic stroke.

Methods:
From the GISCOME (Genetics of Ischemic Stroke Functional Outcome) study, we investigated the subgroup with probable LVO, defined as NIHSS score of ≥7 in combination with one of the TOAST/CCS stroke subtypes cardio-embolic, large artery atherosclerosis, or undetermined cause, thus excluding patients with small artery occlusion or other known causes. The primary outcome was the modified Rank Scale (mRS) dichotomized as good (mRS score 0-2) versus poor (mRS score 3-6) at 3 months (allowing 60-190 days) post-stroke. We calculated the odds of poor outcome (mRS score 3-6) with a mixed-effects logistic regression model adjusting for stroke severity (total NIHSS), age, sex, hypertension, diabetes, current smoking, and ancestry (principal components 1-5) with study cohort as a random effect.

Results:
Among the 1,530 included patients with probable LVO, the median age was 73 years (inter quartile rage (IQR) 63-82, 771 (50.4%) were men, and the median initial NIH stroke score was 13 (IQR 9-18). At three months post-stroke, 38% had a mRS score of 0-2. The LOC105372028 variant was significantly associated with poor outcome at 3 months (OR 1.27 95% CI 1.02, 1.57), whereas the BDNF and PATJ variants were not (OR 1.10; 95% CI 0.87, 1.38, and OR 1.26 95% CI 0.70, 2.27, respectively).

Conclusions:
The LOC105372028 variant is associated with functional outcome in patients with probable LVO ischemic stroke, whereas the BDNF and PATJ variants are not.
Abstract 13: Prior Bariatric Surgery is Associated With Reduced Risk of Recurrent Stroke Among Elderly Obese Stroke Survivors: A National Inpatient Sample Study (2016-2019)
Authors: Mahadevan Arankesh , Thompson-Edwards Ashley , Reyaz Nafisa , Garikipati Sushmitha , Vanani Samir , Meenashi Sundaram Dakshin , Babu Kalaivani , Rajarajan Srinishant , Dhavapalani Dhayashri , Prem Anand Dharshana , Vasavada Advait , Jain Manisha , Desai Rupak
Published: February 2024

Introduction:
The paucity of large-scale data exploring the effect of prior bariatric surgery on recurrent stroke outcomes in elderly obese stroke survivors led us to address the gap, with an emphasis on the risk of recurrent stroke and its trends.

Methods:
A retrospective study was conducted using National Inpatient Sample data from 2016-2019. Elderly obese stroke survivors (> 65 years) having a recurrent acute ischemic stroke (AIS), with or without prior bariatric surgery (PBS), were identified using ICD-10 codes. We compared recurrent stroke trends, demographic characteristics, and comorbidities between the cohorts, employing multivariable and other statistical analyses.

Results:
The study included 643,505 elderly obese stroke survivors, of which 1.8% (11,820) had PBS. Both groups (PBS vs. no PBS) were predominantly female (59.7% vs. 73.7%), identified as white (76.5% vs. 83.8%), and covered by Medicare (91.7% vs. 90.7%). Despite being the most prevalent comorbidity, hypertension (83.6% vs. 83.2%) was not significantly associated with bariatric surgery status, followed by hyperlipidemia (68.2% vs. 61.6%), diabetes mellitus (60% vs. 52.2%), tobacco use (37.5% vs. 36.4%), prior myocardial infarction (12.8% vs. 15.7%), peripheral vascular disease (8.8% vs. 11.9%), valvular disease (3.9% vs. 3.5%), and drug abuse (1.6% vs. 1.1%). Between 2016 and 2019, recurrent AIS decreased in the PBS group (from 4% to 2.9%, p=0.035) whilst remaining stable in the other group (4.4% to 4.2%, p=0.064). The PBS group exhibited a significantly lower adjusted odds ratio for recurrent AIS (aOR: 0.77, 95% CI: 0.60 - 0.98).

Conclusion:
Prior bariatric surgery in elderly obese stroke survivors was associated with a 23% lower risk of recurrent AIS and a decreasing trend of AIS recurrence over time. These findings could influence clinical practice and contribute to developing secondary prevention strategies for recurrent stroke among these patients.
Abstract 135: Efficacy and Safety of PCSK9 Inhibitors for Stroke Prevention: Systematic Review and Meta-Analysis
Authors: Oparowski Daniel , Testai Sofia , Guman Ilan , Trifan Gabriela
Published: February 2024

Objective:
Investigate the efficacy and safety of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on stroke prevention.

Background:
PCSK9i reduce low-density lipoprotein cholesterol (LDL-Chol) and lipoprotein a (LpA) levels. Their efficacy in reducing the risk of major cardiovascular events has been shown in multiple randomized clinical trials (RCT). However, clinical equipoise remains on the magnitude and mechanisms by which PCSK9i decrease the risk of stroke.

Methods:
We performed a systematic search of biomedical databases from inception to July 15, 2023, to identify RCTs that investigated the efficacy of PCSK9i versus placebo for major cardiovascular event prevention. The primary outcome was total stroke. The safety outcome was the risk of adverse neurological events, as defined by each trial. Effect size was represented by risk ratio (RR), and analysis was done using random-effects meta-analysis. Heterogeneity was assessed by
I
2
and Cochrane Q statistics. Meta-regression analyses were performed to assess the association between LDL-Chol and LpA reduction and stroke risk.

Results:
Overall, 19 studies with 92,786 patients were included. The quality of the evidence was moderate and heterogeneity for all comparisons was low (
I
2
<25%). The mean age was 60.1 years for the PCSK9i group and 59.6 years for the placebo group, with a mean follow-up time of 60.1 weeks. PCSK9i reduced the LDL-Chol levels by 11% and LpA levels by 8%. PCSK9i were associated with a significant reduction in stroke risk (RR 0.71, 95% CI 0.62-0.81,
I
2
=0%), without an increase in mortality (RR 0.94, 95% CI 0.85-1.05,
I
2
=0%). The risk of adverse neurological events was similar between groups (RR 1.02, 95% CI 0.88-1.18,
I
2
=0%). In meta-regression analyses, the stroke risk was not associated with the magnitude of the effect of PCSK9i on LDL-Chol (LDL Chol β=-0.01, 95% CI=-0.03-0.01) and LpA (β=-0.01, 95% CI=-0.06-0.03) levels.

Conclusions:
PCSK9i significantly reduced the stroke risk, without increasing mortality or the risk of adverse neurological events. Our findings also suggest that the beneficial effect of PCSK9i on stroke risk is mediated by LDL-Chol- and LpA-independent mechanisms.
Abstract 141: Physician Transfer versus Patient Transfer for Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Suri M. Fareed K , Lodhi Abdullah , Maqsood Hamza , Ma Xiaoyu , Hubert Gordian J , Gomez Camilo R , Kwok Chun , Ford Daniel , Hanley Daniel F , Mehr David , Shah Qaisar , Qureshi Adnan I
Published: February 2024

Background:
Physician transfer has been explored as an alternate option to patient transfer for the expedient performance of mechanical thrombectomy in acute ischemic stroke patients.

Methods:
We conducted a systematic review to identify studies that evaluate the effect of physician transfer in patients with acute ischemic stroke who undergo mechanical thrombectomy. Data were extracted from relevant studies found through a search of PubMed, Scopus, and Web of Science until March 2023. A statistical pooling with random-effects meta-analysis was performed to examine the odds of reduced time interval between stroke onset and recanalization, functional independence, mortality, and time from stroke onset to recanalization with physician transfer against no patient transfer.

Results:
A total of 12 studies (11 nonrandomized observational studies, and 1 non-randomized controlled trial) were included. Physician transfer significantly reduced the time interval between stroke onset and recanalization with a pooled standardized mean difference estimate of -0.60 (95% CI [-1.17, -0.04], p = 0.035, 8 studies involving 1419 patients, and with high between-study heterogeneity in the estimates (I
2
=91.7%). The odds for functional independence at 90 days were significantly higher (OR 1.29, 95% CI 1.00-1.66, p = 0.046, 7 studies involving 1222 patients) with physician transfer with low between-study heterogeneity (I
2
=0%). Physician transfer was associated with higher odds of near complete or complete angiographic recanalization (OR 1.18, 95%CI 0.89-1.57, p = 0.25, I
2
=2.8%, 11 studies, 1856 subjects).

Conclusions:
We found a significant reduction in the mean time interval between symptom onset and recanalization associated with physician transfer with increased odds for functional independence at 90 days among patients undergoing mechanical thrombectomy.
Abstract 152: Endovascular Therapy versus Medical Management for Acute Ischemic Stroke With Large Infarct: A Time-Benefit Relationship Analysis
Authors: Yuan Guangxiong , Sang Hongfei , Nguyen Thanh , Huo Xiaochuan , Pan Yuesong , Wang Mengxing , Qiu Zhongming , Liu Lei , Saver Jeffrey L , Miao Zhongrong , XueLi Cai
Published: February 2024

Objective:
Recent randomized trials demonstrated the benefit of endovascular thrombectomy for acute ischemic stroke with large infarct. We aimed to characterize the effect of time to treatment on the benefit of endovascular therapy compared to medical management among patients with acute large ischemic stroke.

Methods:
Analysis the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core trial (ANGEL-ASPECT), which was a multicenter, randomized trial at 46 comprehensive stroke centers in China from August 2020 to October 2022. Onset to arterial puncture time (OPT) associated with outcomes of endovascular therapy were analyzed as a category and continuous variable. The primary outcome was favorable outcome (modified Rankin scale 0-3) at 90 days. Secondary outcomes included degree of disability (modified Rankin scale range), symptomatic intracranial hemorrhage, any intracranial hemorrhage, and mortality.

Results:
Among 455 eligible patients, the median age was 68 years, and median Alberta Stroke Program Early Computed Tomography Score was 3 (interquartile range 3-4). Compared with medical management alone, endovascular therapy plus medical management was associated with higher rates of favorable outcome with OPT within 6 hours (44.4% vs 29.9%, adjusted odds ratio[aOR] 2.78 [95% confidence interval [CI] 1.22-6.32]), 6-12 hours (45.7% vs 29.6%, aOR 2.39 [95% CI 1.21-4.71]), but not in OPT beyond 12 hours (51.6% vs 41.4%, aOR 2.05 [95% CI, 0.88-4.77]). The benefit in favorable outcome became nonsignificant after OPT of 13 hours and 22 minutes. In three OPT intervals, the odds of better disability outcome with endovascular therapy plus medical management than medical management alone were observed; the rates of symptomatic intracranial hemorrhage and mortality were similar, though the rates of any intracranial hemorrhage increased.

Conclusion:
In patients with large cerebral infarction, endovascular therapy plus medical management was efficacious in improving functional outcomes with acceptable safety in a broad time window of 0 to 24 hours, but greater benefit was observed with earlier treatment. A pooled analysis with larger sample size is needed.
Abstract 2: Intracranial Hemorrhage Managed By A Mobile Stroke Unit
Authors: Sambursky Jacob A , Yamal Jose-Miguel , Wang Mengxi , Parker Stephanie , Jacob Asha , Rajan Suja S , Bowry Ritvij , Grotta James C , Czap Alexandra L
Published: February 2024

Background:
Mobile stroke units (MSUs) improve outcomes in thrombolytic-eligible ischemic stroke patients. Outcomes of MSU management in patients with intracranial hemorrhage (ICH) have not been reported.

Methods:
We conducted a retrospective review of ICH patients enrolled in the Benefits of Stroke Treatment Using a Mobile Stroke Unit (BEST-MSU), a prospective multicenter controlled trial comparing MSU with standard EMS management (SM). The primary outcome was utility weighted modified Rankin Scale (uw-mRS) at 90 days; secondary outcomes were hematoma expansion, length of inpatient stay, favorable discharge disposition or 90-day mRS, and mortality. Groups were compared using Chi-square or Fisher’s exact tests for categorical variables, and two sample t-test or Wilcoxon rank sum test for continuous variables. Adjusted analysis was performed to evaluate the relationship between the intervention group and uw-mRS at 90 days. Kaplan-Meier curves and log-rank test were used to compare the survival by 90 days between groups.

Results:
201 ICH patients were identified; 102 in the MSU and 99 in the SM groups. MSU patients had more antiplatelet/antithrombotic (AP/AT) use (30.4% vs 15.2%, p=0.016); edema was more frequent in the SM group (72.7% vs 52.0%, p = 0.004). Initial ICH volume was similar between MSU and SM groups (11.50 mL [5.0, 22.0] vs. 9.0 mL [5.0, 20.0], p = 0.62). Anti-hypertensives were given earlier on the MSU (39.0 min [31.00, 45.00] vs 61.0 min [46.50, 75.25], p<0.001), and resulted in shorter time to systolic blood pressure (SBP) < 150mmHg (52 min vs. 121 min, p<0.001). The mean uw-mRS at 90 days was 0.364 ± 0.361 in the MSU and 0.465 ± 0.360 in the SM group (p=0.50, adjusted for AP/AT and edema). There was no difference in hematoma expansion, length of stay, discharge disposition or 90-day mRS. Higher mortality was noted after 5 days post-ictus in the MSU group (26.5% vs. 14.1%, p = 0.04).

Conclusion:
In ICH patients, MSU management resulted in faster treatment and time to target SBP with similar clinical outcomes except higher late mortality. Further study of the impact of prehospital ICH management including BP reduction and AT/AP reversal are required.
Abstract 28: Patients Randomised to Glenzocimab Suffered Less Haemorrhagic Transformation at 24 Hours Compared to Placebo: AI-Imaging Sub-Analysis of the ACTIMIS Trial
Authors: Comenducci Andrea , Meilhoc Adeline , Pletan Yannick , Binay Sophie , Avenard Gilles , Perry Alistair , Namias Rafael , Joly Olivier , Harston George , Carone Davide , Mazighi Mikael
Published: February 2024

Introduction:
ACTIMIS (NCT03803007) was a randomized phase 1b/2a clinical trial evaluating glenzocimab, a monoclonal antibody fragment targeting platelet receptor glycoprotein VI in patients with acute ischemic stroke treated by thrombolysis. Primary analysis demonstrated a reduction in intracranial hemorrhage occurrence stroke-related mortality. In this sub-analysis, volumetric imaging biomarkers were used to assess efficacy of glenzocimab.

Methods:
In the phase 2a study, patients were randomized (1:1) with 1000mg glenzocimab or placebo. CT or MRI was acquired at baseline with CT at 24 hours and MRI at 7 days for safety and efficacy analysis. Baseline and follow up imaging were processed as post-hoc analysis using AI core lab software (Brainomix, Oxford, UK). Automated output was reviewed for accuracy by an expert clinician (DC) blinded to treatment allocation.

Results and Conclusions:
Follow up imaging data were available from 103/106 patients (51 glenzocimab, 52 placebo) at 24 hours. Of these, 54 underwent mechanical thrombectomy (MT, 27 glenzocimab, 27 placebo). Day-7 imaging was available for 9 fewer placebo patients and 1 glenzocimab patient. All except 2 patients (1 placebo, 1 glenzocimab) with missing data at Day-7 died during the study. Preliminary analysis showed smaller volume of hemorrhagic transformation (HT) in the glenzocimab group at 24 hours compared to placebo and a trend towards smaller volume of ischemic injury. Exploratory analysis also highlighted an interaction effect between risk of HT following MT and glenzocimab (lower risk in patients treated with glenzocimab). The full results of the imaging sub-analysis of the ACTIMIS study will be presented at the conference and discussed in the context of current literature.
Abstract 30: Pharyngeal Electric Stimulation: The Initial U.S. Experience With a Novel Device for Treatment of Severe Dysphagia After Stroke
Authors: Alexandrov Andrei V , Knoll Jaclyn , Tousley Brenda , Bushnell Cheryl D , Canosa Kati , Mixon Kathryn , Giurgiutiu Dan-Victor
Published: February 2024

Background:
Based on over 20 years of international research, FDA recently granted De Novo classification to the Phagenyx® Neurostimulation System for pharyngeal electrical stimulation (PES) for patients with severe dysphagia post stroke.

Subjects & Methods:
We report on the design and outcomes of the first U.S. post market multi-center experience with the Phagenyx® Neurostimulation System (Phagenesis Limited, Manchester, UK). Eligible patients were determined to have severe dysphagia post-stroke (ischemic or hemorrhagic) by the treating stroke neurologists (MD) and standard assessments by Speech-Language Pathologists (SLPs). Treatment was implemented in addition to standard of care during hospitalization with institutional informed consents obtained prior to treatment. PES stimulation levels were optimized for each patient and each treatment through sensory threshold and tolerance testing by the SLPs. This was followed by a fixed 10 minute treatment session. The treatment regimen was: 1 treatment per day, 10 min/day x 3 days with interim speech therapy reassessment. Treatment could be extended up to 3 additional treatments for a total of 6 treatments if deemed necessary by medical team. SLPs monitored for adverse events during the optimization and treatment.

Results:
PES was administered to a minimum of 5 patients at each participating institution during the initial implementation. An instrumental assessment was completed at the conclusion of the treatment period as indicated, showing outcomes that ranged from improved secretion management and diet advancement, to swallow restoration. Patient experiences and suggestions were captured and will be presented.

Conclusions:
A novel FDA-approved PES device for treatment of severe dysphagia shows a potential to be safely tolerated with the magnitude of swallowing improvement and restoration similar to the pivotal trials conducted overseas. Final results of the multi-center study will be presented at the meeting.
Abstract 34: Achieving a 30 Minute Door to Needle Time in a Primary Stroke Center via Telestroke
Authors: Powell Kayla , Hackett Chris , Quigley Kirsten , Stinson Danielle , Sullivan Richard , Chandra Rahul , Stricklin Lisa , Goldwasser Jason
Published: February 2024

Background:
Despite efforts made within the Emergency Department (ED), delays in the administration of thrombolytic time via telestroke remain. A Primary Stroke Center (PSC) aimed to reduce door-to-needle time (DTN) by focusing on ED, EMS, CT and physician staff regarding: door-to-CT process, importance of time goals, IV thrombolysis, and early activation of Telestroke.

Methods:
A retrospective analysis examined patients who arrived to a PSC and received a telestroke consult in the ED from January 2020 to June 2023. A change in the stroke alert process (January 2023) focused on early notification of stroke alert, CT and telestroke. Thus we compared data from prior to the change in process (January 2020 - December 2022) to after changing the process (January 2023 - June 2023). Primary outcome was a comparison of door-to-needle time (DTN) before and after changing the stroke alert process which was analyzed using a quantile regression specifying the median. Secondary outcomes included: DTN goals within 30, 45, 60 minutes and proportion of IV thrombolysis utilizing hierarchical binomial logistic regressions. Additional outcomes were door-to-CT head (DTCT) and door-to-telestroke (DTSR) analyzed via median regression adjusted for age, NIHSS and arrival modality. All outcomes were adjusted for age, NIHSS and arrival modality (EMS versus private vehicle).

Results:
Overall 1160 ED telestroke consults occurred the study, with a mean age ± SD of 68.75 ± 15.48. There were 989 consults before and 171 consults after the process change. After changing the ED stroke process, there was a reduction in DTN of 29.26 minutes [95% Confidence Interval (CI), 17.45 - 41.08], p < 0.0001. DTN goals of 30, 45 and 60 minutes were met more often after the change compared to prior, all adjusted p < 0.005. A higher proportion of IV thrombolysis rates occurred after the process change [21 (12.3%) versus 79 (8.0%)], adjusted Odds Ratio (aOR) = 2.18 [95%CI 1.27 - 3.75], p = 0.005. There were significant reductions in DTCT and DTSR after changing the process, all p < 0.001.

Conclusion:
A standardized workflow with emphasis on early stroke alert and CT resulted in a significant reduction of DTN, and allowed a PSC with telestroke to consistently achieve DTN < 30 minutes.
Abstract 41: Conventional vs Advanced Imaging for the Selection of Stroke Therapy in the Extended Window (VESTA Study)
Authors: Hernandez-Perez Maria , Valls Carbo Adrian , Castaño Carlos , Boher Marc , Aja Lucia , Remollo Sebastian , Terceño Mikel , Gramegna Laura L , Boix Marti , Pastrana Miriam , Rodriguez-Caamaño Isabel , de Dios Lascuevas Marta , Bashir Saima , Beltran Brigitte , Millan Monica , Perez de la Ossa Natalia
Published: February 2024

Background:
The optimal imaging modality for treatment selection in the extended stroke window is uncertain. VESTA study (NCT05299034) compared conventional imaging (noncontrast CT + CT angiography) with advanced imaging (adding perfusion) in extended window stroke patients, focusing on EVT selection rate, safety and functional outcome.

Methods:
From the prospective Catalan Stroke Registry (CICAT, 29 centers) ischemic stroke patients within 6-24h of symptom onset and NIHSS ≥6 (Jan 2019 -Dec 2021) were selected. Imaging modality was decided according to the local site protocol. Images were re-evaluated by a central core lab with full access to each patient’s images. LVO was defined as intracranial ICA, M1 or proximal M2 occlusion. Blinded investigators centrally assessed 90-day functional independence, defined as mRS≤2. We employed a propensity score matching algorithm to adjust for age, sex, NIHSS, established infarct, and time from onset to arrival.

Results:
We included 1405 patients in the analysis (median age 76y, median NIHSS 11; 48% women). Conventional imaging was performed in 48% of patients, while 52% received advanced imaging. Patients receiving conventional vs. advanced imaging showed lower NIHSS (11 vs. 12, p=0.006), and lower rates of LVO (45% vs. 58%, p<0.001) and EVT indication (33% vs. 41%, p=0.01). Demographics and time metrics were comparable between techniques. The matched adjusted analysis showed no differences between modalities in 90-day functional independence (OR=0.9 [0.7;1.2]), mortality (1.18 [0.9;1.6]), or symptomatic hemorrhage (OR=1.35 [0.47;3.8]). The figure displays subgroup analysis for patients arriving at a comprehensive stroke center and for patients with anterior LVO.

Conclusions:
Advanced imaging allowed the identification of more occlusions and the selection of more patients for EVT; however, patients undergoing either conventional or advanced imaging had similar clinical outcomes at 90 days.
Abstract 49: 15-Year Trends in Age and Sex-Specific Utilization of Carotid Revascularization Procedures in the United States
Authors: Otite Fadar , Chaturvedi Seemant
Published: February 2024

Background:
In July 2023, the Center for Medicare and Medicaid Services (CMS) proposed broader coverage for carotid artery stenting (CAS) for patients with symptomatic (Sx) and asymptomatic carotid disease (Asx) in the United States (US)

Objectives:
This study provides a 15-year snapshot of current CAS and carotid endarterectomy (CEA) use in various age and sex groups of the US.

Methods:
We identified all Sx and Asx CAS and CEA admissions in adults (≥18 years) from the 2006-2020 National Inpatient Sample using International Classification of Diseases codes. We calculated the age and sex-specific proportions of revascularizations that were CAS and combined annual CAS/CEA counts with census data to determine annual utilization rate per 100,000 population. We used Joinpoint regression to estimate annualized percentage change (APC) in usage over time.

Results:
Of 1,591,651 weighted procedures over the study period, 30% were done in 60-69 year olds and 20% in ≥80 year olds. This age distribution was constant over time. 15.1% of all procedures were CAS but this proportion doubled over time such that in 2020, 29.6% of all procedures were CAS. CAS proportion increased in all age groups including those >70 years and in women, even after excluding patients with tandem occlusions (Figure 1). 22.5% of CAS and 11.7% of CEA were done in Sx patients but this proportion increased over time in both CAS and CEA (p-trend <0.001). Annual usage of CEA declined from 51.6 to 22.5 cases/100,000 population in both sexes combined (APC -5.4%, 95%CI -6.0 to -4.8), while CAS use declined from 2006-2016 but increased significantly over 2016-2020 in both men (APC 16.5%, 95%CI 10.0 to 23.3) and women (APC 15.2%, 95%CI 10.2 to 20.4) (Figure 1).

Conclusion:
Despite uncertain benefit in selected age and sex groups including those > 70years, CAS use has continued to increase in all age and sex groups and now accounts for one-third of carotid revascularizations . With the CMS change CAS use could increase further.
Abstract 55: Cerebral Autoregulatory Curves in Postpartum Individuals With and Without Preeclampsia
Authors: Woolcock Helen , Katsidoniotaki Maria , Haghighi Noora , Almonte Casandra , van Wingerden Anne-Sophie , Valdes Eduard , Alian Aymen , Booker Whitney , Bello Natalie A , Marshall Randolph , Kougioumtzoglou Ioannis , Petersen Nils H , Miller Eliza C
Published: February 2024

Introduction:
Risk of maternal stroke is higher in patients with preeclampsia (PEC), with the highest risk seen in those with chronic hypertension with superimposed preeclampsia (siPEC). Most strokes occur postpartum. Changes in cerebral autoregulation (CA) could contribute to elevated postpartum stroke risk. We describe CA curves in postpartum patients with no hypertension, PEC and siPEC.

Methods:
We prospectively recruited postpartum patients with and without PEC and measured 10-minute continuous mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) with finger plethysmography and transcranial Doppler within 1 week of delivery. We generated polynomial S-curves to derive limits of CA, CA plateaus (defined as slope < 0.15), and mean and minimum slopes between CA limits. We calculated Pearson correlation coefficients (Mx) between normalized MAP and CBVF; Mx > 0.3 indicates high MAP-CBFV correlation, suggesting impaired CA.

Results:
CA curves were produced from 71 patients (28% normotensive, 42% PEC, 30% siPEC). Group means for MAP were higher in those with PEC and siPEC (normotensive 72 mmHg, PEC 88, siPEC 87 [p=0.001]). CA was preserved in all groups, with Mx nadirs below 0.3 (Figure). The normotensive group demonstrated a wide, flat plateau in the S-curve (minimum slope 0.02). In the PEC group, we observed a narrower and slightly steeper autoregulatory plateau (minimum slope 0.05). The siPEC group displayed the narrowest and steepest plateau (minimum slope 0.15).

Conclusion:
In conclusion, in our sample of postpartum patients with normotension, PEC and siPEC, we observed a gradient in CA plateau range and slope. Compared with the normotensive group, the PEC and siPEC groups had progressively narrower and steeper CA plateaus, suggesting a more limited CA range and diminished CA efficacy. Future studies should investigate whether sustained MAP outside CA limits contributes to adverse maternal outcomes, particularly in those with siPEC.
Abstract 57: Rapid Prehospital Diagnosis of Intracerebral Hemorrhage by Measuring GFAP on a Point-of-Care Platform
Authors: Kalra Love-Preet , Zylyftari Sabina , Blums Kristaps , Barthelmes Stephan , Humm Sebastian , Baum Hannsjoerg , Meckel Stephan , Luger Sebastian , Foerch Christian
Published: February 2024

Background:
The rapid differentiation between intracerebral hemorrhage (ICH) and ischemic stroke (IS) in patients with symptoms of acute stroke is decisive for triage and initiation of targeted therapies. Glial fibrillary acidic protein (GFAP) is a highly promising blood biomarker indicating acute ICH. In this study we investigated the potential of a new GFAP plasma test on a point-of-care (POC) platform for rapidly distinguishing ICH from IS in the prehospital phase.

Methods:
Patients with symptoms of acute stroke admitted within 6 hours of symptom onset were enrolled. Blood samples were collected already in the prehospital phase in most patients. Plasma GFAP measurements were performed on the i-STAT Alinity® (Abbott) device (duration of analysis 15 min). The primary endpoint was the final diagnosis at hospital discharge categorized as ICH, IS or stroke mimics.

Results:
155 patients were enrolled (mean age 75±13, 49% females; final diagnosis 33 ICH, 115 IS, 7 stroke mimics). Prehospital GFAP serum concentrations were strongly elevated in ICH patients compared to IS patients (mean 2283±3821 pg/mL, median 144 [IQR 52.5-2562] vs. mean 45±25 pg/mL, median 29 [IQR 29-53]; p<0.001). In patients with a moderate to severe neurological deficit (NIHSS > 7), GFAP values below 30 pg/mL were associated with a negative predictive value of 100% (i.e. ruling out ICH). The probability of ICH increased in parallel with higher GFAP levels. GFAP concentrations above 120 pg/mL indicated ICH with a positive predictive value of 94%.

Conclusion:
Rapid prehospital GFAP measurements on a point-of-care platform allow a reliable differentiation between patients with IS and ICH. This opens the potential for optimized triage and for the administration of antidots in severely affected patients with suspected anticoagulation-associated ICH.
Abstract 59: Contemporarypre-Stroke Antiplatelet Use and the Risk of Symptomatic Hemorrhagic Transformation After Intravenous Thrombolysis
Authors: Peng Teng J , Schwamm Lee H , Fonarow Gregg C , Hassan Ameer E , Hill Michelle , Messe Steven , Coronado Fatima , Falcone Guido J , Sharma Richa
Published: February 2024

Introduction:
Many patients are taking antiplatelet medications when an acute stroke occurs. We evaluated the risk of hemorrhage associated with newer, more potent antiplatelet medications and dual antiplatelet regimens among patients treated with intravenous tissue plasminogen activator (IV-tPA).

Methods:
Using the American Heart Association Get With The Guidelines-Stroke Registry from January 1, 2013 to December, 31 2021, we analyzed data on all ischemic stroke patients hospitalized and treated with IV-tPA. The exposure of interest was pre-stroke antiplatelet use categorized as none, single (SAPT), and dual antiplatelet therapy (DAPT). The primary outcome of interest was symptomatic intracranial hemorrhage (sICH) within 36 hours of tPA administration. A secondary outcome was modified Rankin Scale (mRS) at discharge. Propensity score matching was performed to mitigate confounding by indication for each pre-stroke antiplatelet treatment strategy. Adjusted multivariate logistic regression analyses were performed to evaluate associations between pre-stroke antiplatelet medication and outcomes of interest.

Results:
The analytic cohort included 320,493 patients who had an acute ischemic stroke and received IV-tPA. The pre-stroke antiplatelet therapy utilization frequencies were 56.9% no antiplatelet, 36.7% SAPT, and 6.4% DAPT. The frequency of sICH was 2.9%, 3.8%, and 4.1% among patients treated with none, SAPT, and DAPT respectively (p<0.001). After performing propensity score matching, both SAPT (OR 1.13, 95% C.I. 1.08-1.20) and DAPT (OR 1.28, 95% C.I. 1.14-1.43) were associated with increased risks of sICH. DAPT was also associated with a significantly higher risk of sICH compared with SAPT (OR 1.18, 95% C.I. 1.08-1.28). Use of pre-stroke antiplatelet medications was associated with lower odds of discharge mRS
<
2 compared to none: (SAPT OR 0.92, 95% C.I. 0.89-0.96; DAPT OR 0.93, 95% C.I. 0.87-0.98).

Conclusion:
In this study, pre-stroke antiplatelet use was associated with a modest, dose-dependent risk of sICH and functional dependence.
Abstract 6: Financial Concerns Are Common Among Family Members of Severe Stroke Patients: A Mixed Methods Study
Authors: Becker Christopher J , Baker Jessica E , Springer Mellanie V , Zhang Guanghao , Shi Xu , Kwicklis Madeline , Case Erin , Morgenstern Lewis B , Zahuranec Darin B
Published: February 2024

Background:
Stroke has a large aggregate financial impact, however the prevalence and predictors of cost concerns among family members of severe stroke patients are unknown.

Methods:
Family surrogate decision makers of severe stroke patients were recruited from the BASIC and OASIS projects in a South Texas community. Clinical information was obtained from medical charts. Patient and family member sociodemographic information was obtained from surveys, conducted at baseline and 3-, 6-, and 12-months post-stroke. The primary outcome was presence of cost concerns among family members, defined as being “very worried” or “moderately worried” about being able to pay stroke-related medical costs at any time point. Exploratory multivariable logistic regression models identified factors associated with cost concerns. A subset of participants also completed qualitative semi-structured interviews exploring the nature of cost concerns.

Results:
Of 2,917 stroke cases between April 2016 and September 2020, 465 were eligible, and 318 family members of 256 stroke patients participated. Patients were 52% female, 58% Mexican American (MA), with mean age of 75 (SD 14), and mean National Institutes of Health Stroke Scale score of 15 (SD 11). Family members were 76% female, 63% MA, with mean age of 56 (SD 13). Of 256 patients, 118 (46%) had a family member who reported having cost concerns. In a fully adjusted model (see Table), MA ethnicity and lack of insurance were associated with greater cost concerns. Cost concerns were less common over time and with patient death, and were less common among family members who were neither a spouse nor child of the patient. Interview data revealed that concerns were most often related to costs of post-acute care (excerpts included in the Table).

Conclusions:
Nearly half of all severe stroke patients have a family member with concerns about affording their medical care. Providers should seek to elicit cost concerns and provide resources to address them.