bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP12: Large Vessel Vasculopathy is Associated With Oxygen Metabolic Stress in Children and Young Adults With Sickle Cell Disease
Authors: Wang Yan , Fellah Slim , Guilliams Kristin , Fields Melanie , Astafiev Serguei V , Jamro Erica L , Mirro Amy , Lewis Josiah B , Cohen Rachel , Hulbert Monica L , King Allison A , Reis Martin N , Chen Yasheng , Lee Jin-moo , An Hongyu , Ford Andria L
Published: February 2024

Background:
Large-vessel vasculopathy (LVV), such as moyamoya syndrome, increases stroke risk with sickle cell disease (SCD). We hypothesized that tissue-based cerebral blood flow (CBF) and oxygen extraction fraction (OEF), as indicators of hemodynamic and metabolic stress, would differ in hemispheres with vs. without LVV.

Methods:
Patients underwent serial brain MRI and time-of-flight MRA to quantify voxel-wise CBF, OEF, and infarcts. LVV was defined as 75-99% stenosis of a major anterior circulation artery. Hemispheres with large vessel occlusion or revascularization surgery were excluded. Infarcted voxels were removed. Mean hemispheric (hemi-) CBF, OEF of the anterior circulation were extracted based on a vascular territory template. Hemi- OEF was normalized to whole brain OEF (nOEF). Hemi- cerebral metabolic rate of oxygen utilization (CMRO
2
) was calculated from arterial oxygen content, hemi- CBF, and hemi- OEF. Mann-Whitney
U
was used to compare hemispheres with vs. without LVV. Effects of age, hemoglobin, and repeated MRIs were adjusted for in linear mixed model.

Results:
Of 158 patients, 221 MRI and MRAs were performed. At baseline, LVV occurred in 5% of hemispheres. Median infarct volume was larger in hemispheres with vs. without LVV (6.5 vs. 0.04 mL,
p
<0.001). In baseline univariate analysis, hemispheres with LVV had lower CBF (25.8 vs 31.3 mL/100g/min,
p
=0.04), non-significantly higher nOEF (0.99 vs. 0.96,
p
=0.067), and lower CMRO
2
(8.1 vs. 12.4 mL/100g/min,
p
=0.002) vs. without LVV. In mixed model, with all MRIs included, LVV was independently associated with nOEF (β = 0.03,
p
=0.04) and showed a trend for association with CBF (β = -5.4,
p
=0.09) and CMRO
2
(β = -35.2,
p
=0.08).

Discussion:
In SCD, hemispheric OEF was increased as a compensatory response to flow-limiting stenosis, yet may be inadequate to prevent infarction as CMRO
2
decreased. Hemispheric OEF, as an indicator of increased stroke risk, may guide medical management and surgical intervention.
Abstract TMP13: Prehospital Stroke Scales Are Non-Inferior to NIHSS in Prediction of Intravenous Thrombolysis Use in a Large Telestroke Network
Authors: English Stephen W , Chhabra Nikita , Hanus Abigail , Basharath Rida , Miller Monet , Butterfield Richard , Zhang Nan , Demaerschalk Bart M
Published: February 2024

Introduction:
Recent studies report similar outcomes with antiplatelet drugs and intravenous thrombolysis (IVT) in patients with minor nondisabling ischemic stroke. These patients still meet emergent triage criteria and can increase the burden on stroke systems through prehospital stroke activation. Prehospital large vessel occlusion (LVO) scales can improve triage of LVO patients but have not been evaluated as tools to predict IVT administration. We sought to determine if common LVO scales can predict IVT use in a large academic telestroke practice.

Methods:
This retrospective study included all video telestroke consults performed in a large academic telestroke network from 2019-2020. Patients were excluded if they were on anticoagulation, presented beyond 4.5 hours from last known well, or family declined IVT due to goals of care. We recorded presenting NIHSS and IVT recommendations. NIHSS was used to calculate 7 LVO scales (RACE, G-FAST, FAST-ED, VAN, PASS, 3I-SS, and C-STAT). Scale performance was assessed by calculating area under curve (AUC) and compared to NIHSS total score using the DeLong test. Youden cutpoint was established for each scale and subsequently used to calculate sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy.

Results:
A total of 513 patients were included; 205/513 (40%) were recommended IVT. Median (IQR) NIHSS was 1 (0-3) in non-IVT patients and 6 (4-11) in IVT patients. The RACE and G-FAST scales were noninferior to the NIHSS in predicting IVT recommendation (Table 1).

Conclusion:
The RACE and G-FAST scales may be useful triage tools to identify patients needing emergent stroke evaluation for consideration of IVT.
Abstract TMP17: Predicting Neurosurgical Intervention After Intracerebral Hemorrhage (ICH) Transfer
Authors: Puissant Madeleine , Barry Samantha , Birkbeck Duncan , Jalal Safanah , Sawyer Jared , Morris Jane G
Published: February 2024

This is a retrospective chart review to ascertain the rates of neurosurgical intervention following transfer of patients with non-traumatic intracerebral hemorrhage (ICH) to a Comprehensive Stroke Center (CSC) and characterize predictors of need for surgical intervention.

Introduction:
While neurosurgical intervention is required in a minority of cases, it has become standard practice for all ICH patients to be transferred to our tertiary care center, without consideration of additional factors. This creates significant burden and stress to patients and families as well as hospital resources.

Hypothesis:
We hypothesize that only a minority of ICH patients require neurosurgical intervention and that we will be able to identify predictors that will assist in identifying patients who are at risk for needing neurosurgical intervention.

Methods:
We retrospectively reviewed the EMR from all ICH patients transferred to a 700-bed CSC from 2020-2023. We collected: age, sex, pre-stroke modified Rankin score, ICH score, BP management, anticoagulant reversal, any neurosurgical intervention performed, length of stay (LOS), and 30-day mortality. The data was stored and analyzed in a secure online database.

Results:
Of the 420 completed charts, 55% of patients were male with an average age of 67.7 years. Only 14.25% (61/420) of all patients underwent neurosurgical intervention. Predictors for surgery included: age (average age of patients who underwent surgery was 61.2 years); size and location of the hematoma (the majority of patients who underwent surgery (58/61) had ICH volume >30cc, were subtentorial in location, or had IVH extension); higher ICH score (23.96% with ICH ≥2 vs. 6.67% with ICH 0-1); and lower GCS (41.5% GCS <12 vs. 9.8% GCS ≥ 12). Average hospital length of stay was 10.5 days. Mortality rate at 30-days was 24.5% overall and higher in patients who underwent neurosurgical intervention (32.8%).

Conclusion:
Only a small percentage of patients with ICH transferred to our CSC require neurosurgical intervention. There are many predictive factors allowing for a more thoughtful approach to better utilize health care resources. We recommend further studies to develop better strategies to triage these patients.
Abstract TMP19: Need for Enhancing Mental Health Care in Stroke Patients: Insights Into Post-Stroke Anxiety and Depression From the National Health Interview Survey (NHIS) Data
Authors: Kurra Nithin , Gandrakota Nikhila , Ramakrishnan Manju , Konatham Sravani , Sevella Prerana , Jillella Dinesh
Published: February 2024

Background:
Stroke is a leading cause of chronic disability, with neuropsychiatric presentations being increasingly recognized as complications that hinder rehabilitation and patient outcomes. This study investigates factors influencing anxiety and depression prevalence in stroke patients.

Methods:
Utilizing 2019 National Health Interview Survey (NHIS) data, we conducted chi-square tests and multivariate logistic regression models, adjusting for various factors. We also assessed the proportion of anxiety and depression patients undergoing therapy and/or medication.

Results:
There were 1204 (N=7,745,925) participants with stroke and 30,743 (N=242,831,595) without stroke. After applying appropriate sample weights, we identified that patients aged 65-75 and >=75 had similar odds but demonstrated decreased likelihood of depression compared to younger patients with stroke (OR=0.4, 95%CI (0.2,0.9). Moreover, stroke patients with high school education or higher were less likely to have anxiety (OR=0.6, 95%CI (0.4,0.9) while patients with medicare/medicaid were more likely to have anxiety (OR=2.9, 95% CI (1.1,7.7) after adjusting for demographic factors. Therapy use was suboptimal with only 24.2% and 43.4% of stroke patients with mild-moderate and severe anxiety, respectively, currently receiving therapy. For depression, therapy was sought by only 20.0% and 35.9% with mild/moderate and severe depression, respectively. Furthermore, medication use was noted in 42.6% and 48.4% of patients with stroke with mild-moderate and severe anxiety, respectively while 35.3% and 59.3% of stroke patients with mild-moderate and severe depression were taking medication.

Conclusion:
Demographic factors were found to significantly affect the prevalence of anxiety and depression among stroke patients with sub-optimal utilization of therapy and treatment. Appropriate guidelines are necessary for routine screening and treatment of anxiety and depression among stroke patients.
Abstract TMP31: Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID): A Potential Neuroprotection Strategy for Acute Ischemic Stroke (AIS) Patients
Authors: Cai Lipeng , Ding Yuchuan , Tong Yanna , Duan Honglian , Han Zhenzhen , Gao Jie , Cheng Zhe , Geng Xiaokun
Published: February 2024

Background:
Despite advances in intravenous thrombolysis and endovascular thrombectomy, numerous acute ischemic stroke survivors continue to experience various disability levels. The nitric oxide (NO) donor, Glyceryl Trinitrate (GTN), has been identified as a potential neuroprotective agent against ischemic damage. This study evaluates the safety and preliminary efficacy of intravenous GTN administration in AIS patients.

Methods:
We conducted a prospective, double-blind, randomized controlled trial at Beijing Luhe Stroke Center (ChiCTR2100046271). AIS patients within 24 hours of onset were evenly divided into GTN or control groups (n=20 each). The GTN group received intravenous GTN (5 mg in 50 ml saline at a rate of 0.4 mg/h for 12.5 h/day over 2 days), while controls were administered an equivalent volume of 0.9% saline. Both groups followed standard Stroke Guidelines for treatment. Safety measures focused on SBP<110mmHg and headache occurrence. Efficacy was assessed via the 90-day modified rankin scale (mRS) and the national institutes of health stroke scale (NIHSS) scores.

Results:
Of the 40 AIS patients, baseline characteristics such as age, gender, risk factors, and mRS scores showed no significant difference between the groups. Safety measures of SBP<110mmHg and headache occurrence were also comparable. Overall, 90-day mRS(1 vs 1) and NIHSS (1 vs1 )did not significantly differ between groups. However, the GTN-treated group showed a superior NIHSS recovery (ΔNIHSS 4.5 Vs 3, p=0.028), indicating that GTN can well-allow patients to recover within the same time frame. Subgroup analyses revealed a noteworthy benefit of GTN in the 90-day NIHSS score for non-thrombolysis patients (1 vs 2, p=0.016). Moreover, GTN benefited mild stroke patients (NIHSS score <6) at 90 days (p=0.025).

Conclusion:
The RIGID study confirms the safety of intravenous GTN for AIS patients. Notably, while overall 90-day mRS and NIHSS scores between the GTN and control groups did not significantly vary, the GTN group displayed a pronounced improvement in NIHSS recovery. Additionally, GTN demonstrated particular efficacy for non-thrombolysis patients and those with mild stroke symptoms, suggesting its potential as a tailored intervention in specific AIS subgroups.
Abstract TMP5: Mutation of
Pdgfrβ
Enhances the Severity of Brain Arteriovenous Malformation on Endoglin Mutant Mice Through Exacerbation of Angiogenesis and Inflammation
Authors: Yadav Alka , Barbosa Do Prado Leandro , Tang Chaoliang , Shaligram Sonali , Liang Rich , Press Kelly , Dhaliwal Jasneet , A Winkler Ethan , Su Hua
Published: February 2024

Background and Purpose:
Brain arteriovenous malformations (bAVMs) are tangles of abnormal vessels shunting blood directly from arteries to veins. Reduction of pericytes is correlated with bAVM hemorrhage. The PDGFB/PDGFRβ signaling plays important roles in regulating pericyte recruitment during angiogenesis.

Hypothesis:
Mutation of PDGFRβ causes cerebrovascular malformation and enhances bAVM severity in endoglin (
Eng
) deficient mice.

Methods:
Three mouse models were used: (1)
Pdgfrβ
F7 (F7) mice that have mutations disrupting most Pdgfrβ signaling, (2)
Pdgfb
icreER;
Eng
f/f
mice that have
Pdgfb
promoter driving, tamoxifen (TM) inducible cre expression in endothelial cells (ECs) and a floxed
Eng
gene; and (3) PdgfbicreER;
Eng
f/f
;F7
+/-
mice were used. Brain angiogenesis was induced by intra-parenchymal injection of AAV-VEGF. BAVMs were induced in PdgfbicreER;
Eng
f/f
and PdgfbicreER;
Eng
f/f
;F7
+/-
mice by inducting EC
Eng
deletion through TM treatment and brain angiogenesis through intra-brain injection of AAV-VEGF. BAVM phenotypes were analyzed 8-weeks after model induction by latex vascular cast to detect arteriovenous shunts, immunostaining to analyze vessel morphology, Prussian blue staining to quantify microhemorrhage and RNAseq to investigate gene expression profiles.

Results:
Dysplastic vessels with reduced pericyte coverage were detected in the brain and brain angiogenic region of F7
+/-
and F7
+/+
mice. AVM like vessels were detected in the brain of 16% F7
+/-
and 66% of F7
+/+
mice. F7 mutation increases bAVM penetrance in
Eng
deficient mice (71% vs 50%), dysplastic vessels and microhemorrhage. RNAseq data revealed that mutation of
Pdgfrb
increased the expression of pro-angiogenic and endothelial cell proliferation genes and genes promote cell migration and inflammation in the bAVMs of
Eng
mutant mice.

Conclusion:
Pdgfrβ
mutation exacerbates the severity of bAVM in
Eng
mutant mice by enhancing angiogenesis and inflammation.
Abstract TMP51: Clinical Factors Associated With Enlarged Perivascular Spaces in a US Population of Caucasian Descent
Authors: Shahjouei Shima , Sadighi Alireza , Chaudhary Durgesh , Dabbagh Ohadi Mohammad Amin , Li Jiang , Abedi Vida , Zand Ramin
Published: February 2024

Introduction:
Enlarged Perivascular Spaces (EPVS), characterized by distinct cerebrospinal fluid-filled structures surrounding intracranial vessels, have garnered growing attention concerning brain aging and cerebrovascular disorders. This study investigates the associations between EPVS and a spectrum of clinical factors and conditions in a large community-based sample in the northeastern United States.

Method:
This research was conducted on a subset of the Geisinger DiscovEHR Initiative Cohort. The total numbers of EPVS were categorized into five grades (0-4) in centrum semiovale and basal ganglia regions. A comparison was established between patients with EPVS and a propensity-score-matched cohort devoid of EPVS. Matching factors included age, gender, body mass index, and hypertension.

Results:
Among 3054 randomly selected participants (mean age 67.5 years, 57.4% women), 1465 (47.9%, mean age 69.6 years, 58% women) exhibited EPVS in their brain imaging. The presence of EPVS was linked to cerebral aneurysm (OR, 2.40; 95% CI, 1.5-4.0), heart failure (OR, 2.0; 95% CI, 1.5-2.8), peripheral vascular disease (OR, 1.5; 95% CI, 1.1-2.15), Parkinson's Disease (OR, 1.9; 95% CI, 1.2-3.1), history of ischemic stroke (OR, 1.18; 95% CI, 1.0-1.4), non-central nervous system malignancies (OR, 1.4; 95% CI, 1.1-2.0), smoking (OR, 1.3; 95% CI, 1.0-1.6), and warfarin use (OR, 0.76; 95% CI, 0.6-0.9). Higher scales of EPVS were notably associated with obstructive sleep apnea (OR, 1.9; 95% CI, 1.0-3.8) and hypertension (OR, 3.1; 95% CI, 1.1-9.9).

Conclusion:
EPVS presence and severity may be associated with several vascular risk factors, providing potential avenues for risk assessment and further research.
Abstract TMP53: MR-ASL Imaging Can Predict the Collaterals in Moyamoya Disease
Authors: Mavuru Sambha Murthy Krishna Mohan , Kalaparti Viswanadh , Thomas Bejoy , Sukumaran Sajith
Published: February 2024

Introduction:
Digital subtraction angiography (DSA) is the gold standard investigation for the diagnosis and prognostication of moyamoya disease (MMD). Magnetic resonance arterial spin labelling (MR-ASL) is a newer non-invasive technique that can predict the perfusion reliably. Our study aims at prediction of collaterals with MR-ASL in addition to parenchymal perfusion deficit.

Methodology:
It is an observational single centre cohort study where consecutive MMD patients with both DSA and MR-ASL done within 3 months of each other were included in the study. Images were reviewed by 2 radiologists independently. MMD severity was graded using Suzuki staging and collaterals were graded using DSA and MR-ASL in 7 different regions [4 areas in basal ganglia level - basal ganglia, M1, A1 and P1], 3 areas at superficial cortical level above basal ganglia [M2, A2, P2]. DSA collateral grading used was: grade 0 - no collaterals visible (absence of any capillary blush) with perfusion deficit, grade 1 - mild to moderate collaterals with some perfusion deficit, grade 2 - extensive collaterals with no perfusion deficit, grade 3 - normal antegrade flow. Collateral grading used on MR-ASL was: grade 0 - no or minimal ASL signal; grade 1 - moderate ASL signal with arterial transit artefact (ATA), grade 2 - high ASL signal with ATA, grade 3 - normal perfusion without ATA.

Results:
Of the 46 MMD patients (males - 22), 92 hemispheres were included. 4 hemispheres were excluded as the patient underwent revascularisation in the corresponding hemisphere. Among the remaining 88 hemispheres, 7 were normal on angiography. At various Suzuki grades, the degree of collaterals graded on ASL changed according to Suzuki staging (p<0.001). Whether collateral grading using ASL can predict the collaterals graded using DSA was tested using Cohen Kappa’s method, and it was found that MR-ASL can predict collaterals graded by DSA with very good agreement in all the regions studied (p<0.001).

Conclusion:
MR-ASL is a simple, safe, effective and reproducible alternative for DSA in determining the collaterals and perfusion status in MMD patients without the untoward effects like contrast exposure.
Abstract TMP61: Induced Hypertension in Acute Ischemic Stroke: Systematic Review and Meta-Analysis
Authors: Casteigne Bryce , Shourav Manjurul , Anisetti Bhrugun , Barrett Kevin M , Eidelman Benjamin H , Williams Lindsy N , Huang Josephine F , English Stephen , Meschia James F , Lin Michelle P
Published: February 2024

Background and Objectives:
It is unclear whether induced hypertension in acute ischemic stroke (AIS) may improve long-term outcomes. We conducted a systematic review and meta-analysis to compare the safety and efficacy of induced hypertension vs standard medical care in patients presenting with acute ischemic stroke within 72 hours of symptom onset.

Methods:
Two reviewers systematically searched PubMed using the prespecified terms “induced hypertension” or “blood pressure augmentation” plus “ischemic stroke” for clinical trials that reported functional independence (mRS 0-2) at 90 days. The safety outcome was symptomatic intracranial hemorrhage (sICH). Pooled odds ratio (OR) and 95% CI across trials were synthesized using fixed-effect model based on Mantel-Haenszel methods. Forest plots were constructed.

Results:
Three clinical trials with 270 AIS patients treated with induced hypertension (n=126) or standard medical care (n= 144) were included. Mean age was 66.6 years, 35.2% were women, and the mean initial NIHSS was 7.5. The rate of functional independence at 90 days was higher in patients treated with induced hypertension (70.6%) versus control (54.9%) (OR 1.88; 95% CI 1.13-3.11; p=0.01). sICH did not differ between patients treated with induced hypertension (<1%) versus control (<1%) (OR 1.03; 95% CI 0.14-7.45; p=0.98).

Discussion:
Among patients presenting with acute ischemic stroke with 72 hours of symptoms onset, induced hypertension resulted in better functional outcome at 90 days than standard medical care and did not increase risk of sICH. Large RCTs to test this observation are ongoing and needed to guide clinical practice.
Abstract TMP67: Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy May Affect Large Cerebral Arteries
Authors: Lopez-Navarro Edgar R , Mayer Silvia V , Barreto Brenno R , Bueno Pedro , Gurel Kursat , Khasiyev Farid , Kozii Khrystyna , Rahman Salwa , Spagnolo-Allende Antonio , Mohr J P , Gutierrez Jose
Published: February 2024

Introduction:
CADASIL is the most common monogenic small-vessel disease (SVD) form. Large and small brain arteries are intimately related, but it is unclear whether people with CADASIL have changes in their large arteries as a result. We hypothesized that CADASIL patients have affected large arteries compared to controls.

Methods:
We conducted a comparative analysis by matching 37 CADASIL patients with 104 lacunar stroke patients from the NYP/ Columbia University Medical Center Stroke Registry Study matched by age +/-3 and sex. We measured the basilar and intracranial carotid artery diameters in both groups in T2 MRI images. We rated cervical artery tortuosity as 0 for no tortuosity, 1 for 45-90°, and 2 for >90°. We ran generalized linear models to compare cases and controls, adjusting for demographics and clinical variables.

Results:
Patients with CADASIL were less likely Hispanic\Latino (10.8% vs. 51.9%, p=<0.001), hypertensive (27% vs. 73.1%, p=<0.001), current smokers (5.4%vs. 22.1%, p=0.024), but more likely to have a prior stroke (56.8% vs. 24%, p=<0.001) than controls—Table 1. In the adjusted model, patients with CADASIL had larger basilar artery diameters (p=0.007) and a statistical trend for greater cervical carotid artery tortuosity—Table 2.

Conclusions:
Although traditionally considered an example of pure SVD, patients with CADASIL have a higher prevalence of cervical tortuosity and intracranial artery dilatation. Whether changes in large arteries result from small artery disease or part of the NOTCH3 mutation phenotype is uncertain. Further investigation is needed to determine if large artery involvement influences the clinical manifestations of CADASIL.
Abstract TMP70: Association of Distal Hyperintense Vessel Sign and Outcomes in Patients With Symptomatic Posterior Circulation Intracranial Atherosclerotic Disease
Authors: Uppal Hardeep , Saherwala Ali , Dang Kevin , Salahuddin Hisham , Dang Michael , Upadhyaya Parth , Moore William , Pinho Marco , Shang Ty T
Published: February 2024

Objectives:
The Distal Hyperintense Vessel (DHV) sign on FLAIR imaging is a radiographic marker of inadequate blood flow due to poor collateral flow distal to the stenotic artery. Previous studies suggest that the DHV sign was associated with early recurrent ischemic stroke in the anterior circulation secondary to intracranial atherosclerotic disease (ICAD). However, its significance in ischemic stroke in the posterior circulation is unknown. Here, we investigate the association of DHV sign in the basilar artery and outcomes at discharge in patients with posterior circulation stroke or TIA secondary to ICAD.

Methods:
We retrospectively reviewed patients with ischemic strokes or TIA attributed to ICAD of the basilar or vertebral arteries admitted to two comprehensive stroke centers affiliated with UTSW Medical Center from 2010 to 2022. Patients were included if they met VERiTAS criteria (≥50% vertebrobasilar stenosis). The DHV sign was defined as positive when the increased intensity in the basilar artery distal to stenosis was higher than the surrounding CSF signal. The DHV sign was evaluated by blinded vascular neurologists and neuro-radiologists. The primary outcome was mRS at discharge. The secondary outcome was the incidence of clinical deterioration during admission, defined as any worsened neurological exam with associated new infarct or infarct expansion in the posterior circulation.

Results:
A total of 135 patients were included in the study. A total of 33 (24%) patients had the presence of the DHV sign on admission MRI. Compared to patients without DHV sign, patients with DHV sign had higher NIHSS scores on admission (median 7 vs 2, p<0.001), higher risk of clinical deterioration during hospitalization (27% vs 2%, p<0.001), higher mRS scores at discharge (median 3.45 vs 1.8, p<0.001) and higher mortality rate (24% vs 0%, p<0.001). In multivariate analysis, the DHV sign was an independent predictor of higher mRS scores at discharge.

Conclusions:
In patients with ischemic stroke or TIA secondary to basilar or vertebral artery atherosclerotic stenosis, the presence of the DHV sign in the basilar artery is associated with more severe disease and poorer outcomes at discharge compared to patients without DHV sign.
Abstract TMP75: Histopathologic and Transcriptomic Characterizations of Cerebral Microbleeds in an E4FAD Murine Model
Authors: Srinath Abhinav , Debiasse Dorothy , Vera Cruz Diana , Bindal Akash , Li Ying , Zha Yuanyuan , Lightle Rhonda , Pytel Peter , Girard Romuald , Awad Issam
Published: February 2024

Background:
Cerebral microbleeds (CMBs) are age-related vascular lesions, predisposing patients to a lifetime risk of hemorrhagic stroke and cognitive decline. The cellular architecture in the lesions and their genetic alterations have not been elucidated, limiting biomarker development and therapeutic targeting. Herein, we report histopathological and transcriptomic signatures of CMBs in a murine model.

Methods:
Seven APOE4
+
/
+
; 5xFAD mice were sacrificed at 8 months and had their brains harvested. Brain tissue was stained with H&E and Prussian Blue for non-heme iron to identify CMBs. Astrocytes (GFAP
+
), microglia (CD163
-
/Iba1
+
), macrophages (CD163
+
/Iba1
+
), B cells (CD20
+
), T cells (CD3
+
), and endothelium (CD31
+
) were stained using multiplexed immunofluorescence. Regions of interest (ROIs) around CMBs and directly adjacent tissue, as well as contralateral control brain tissue, were selected and quantified using QuPath. GeoMx spatial transcriptomics was performed on lesions and contralateral control brain areas in the same mice. The DEG analysis was completed using DESeq2.

Results:
CMBs had higher astrocyte and microglia counts (normalized to ROI area) than control tissue (p<0.05). Microglia showed reactive, amoeboid morphological changes: hypertrophic cell bodies and shorter processes. T cells had a trend toward higher cell counts in CMBs (p=0.12). Macrophages and B cell counts were similar between CMBs and controls. The spatial transcriptomics identified 19 DEGs between CMBs and control tissue (p<0.1, FDR corrected) related to permeability, cell metabolism, apoptosis, and transcriptional regulation.

Conclusions:
This is the first report relating the CMB lesional microenvironment to spatial transcriptomic analyses. Further studies shall aim at confirming these findings in human CMB lesions, and their association with circulating molecules. The results pave the way for enhanced mechanistic insight, biomarker discovery and potential therapeutic targeting.
Abstract TMP92: Dementia and Cognitive Impairment in Stroke: A Systematic Review and Meta-Analysis of Reperfusion Treatment Outcomes
Authors: Betzner William , Bala Fouzi , Beland Benjamin , McDonald Jennifer , Ganesh Aravind
Published: February 2024

Background:
Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) outcomes are unclear in patients with pre-stroke dementia or cognitive impairment. Although these individuals make up ~12% of acute stroke patients, they are often excluded from both stroke trials and routine care. This systematic review and meta-analysis explored reperfusion therapy outcomes in this population.

Methods:
Using the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, this systematic review investigated studies on acute ischemic stroke patients with dementia or cognitive impairment treated with either IVT or EVT. Primary outcome was defined as favorable 90-day outcome (modified Rankin Scale (mRS) score 0-2). Secondary outcomes included 90-day mortality, radiographic intracranial hemorrhage (ICH) and symptomatic ICH (SICH).

Results:
9 articles were included from 825 screened. 5 observational studies of IVT use in patients with (n=1078) and without dementia (n=2805) were selected for a meta-analysis. There were no significant differences in favourable 90-day mRS (adjusted OR 0.61, 95% CI 0.24 to 1.59), 90-day mortality (unadjusted OR of 1.19, 95% CI 0.86 to 1.64), ICH (unadjusted OR 1.32, 95% CI 0.79 to 2.19) and SICH (unadjusted OR of 0.94, 95% CI 0.70 to 1.25). EVT in dementia patients in one study found only increased odds of ICH (adjusted OR 1.57 95%CI 1.03 to 2.40). For patients with cognitive impairment, no significant association was found with assessed outcomes in a pooled analysis of 3 IVT studies and one EVT study found poorer 90-day mRS outcomes.

Conclusions:
This systematic review and meta-analysis suggests no considerable safety concerns for IVT or EVT use in patients with pre-existing dementia or cognitive impairment,

compared to those without. Uncertainty remains in the efficacy of these therapies for these individuals. Rigorous, patient-caregiver informed design, and a more nuanced outcome approach are warranted for future studies.
REGISTRATION:
URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.
Abstract TMP96: Clear Thrombectomy Score: An Index to Estimate Probability of Good Functional Outcome Following Endovascular Treatment in the Late Window for Anterior Circulation Occlusion
Authors: Siegler James E , Koneru Manisha , Qureshi Muhammad , Nogueira Raul , Strbian Daniel , Nagel Simon , Penckofer Mary , Demeestere Jelle , Puetz Volker , Ribo Marc , AbdalKader Mohamad , Marto Joao Pedro , Yamagami Hiroshi , Haussen Diogo C , Olive-Gadea Marta , Winzer Simon M , Mohammaden Mahmoud , Tomppo Liisa , Lemmens Robin , Tanaka Kanta , Martinez-Majander Nicolas , Dusart Anne , Bellante Flavio , Caparros Francois , Henon Hilde , Ramos Joao , Ortega-Gutierrez Santiago , Sheth Sunil , Nannoni Stefania , Vandewalle Lieselotte , Kaesmacher Johannes , Salazar-Marioni Sergio , Virtanen Pekka , Ventura Rita , Zaidi Syed F , Castonguay Alicia , Farooqui Mudassir , Puri Ajit S , Klein Piers , Shu Liqi , Farzin Behzad , Masoud Hesham , Mohlenbruch Markus , Ringleb Peter , Zaidat Osama , Yaghi Shadi , Strambo Davide , Michel Patrik , Raymond Jean , Nguyen Thanh
Published: February 2024

Background:
Endovascular thrombectomy (EVT) has established efficacy across a wide range of patient age, radiological findings, and clinical features. However, EVT may be less effective in extreme scenarios (e.g., large established infarction in later treatment windows), where there are currently limited data.

Methods:
A heterogeneous, multinational observational cohort (CLEAR registry) of consecutive adult patients ≥18 years old who underwent EVT for acute occlusion (2014-2022) of the internal carotid or proximal middle cerebral (M1 or M2) arteries was queried (n=64 sites). A high-fidelity model for predicting good functional outcome at 90 days (return to pre-stroke modified Rankin Scale [mRS] or mRS 0-2 after EVT) was developed using a binary, multivariable logit model with adaptive double lasso adjustment, which was validated using 5-fold cross validation and 1000 bootstrap sampling for confidence intervals.

Results:
At the time of the analysis, we evaluated 2953 patients from the registry treated with EVT, of which 1855 (63%) had complete covariate data for inclusion. The median National Institutes of Health Stroke Scale (NIHSS) score was 15 (IQR 9-20), with 14.0% having a pre-stroke mRS >2, 8.3% having a NIHSS <6, and 17.8% having an Alberta Stroke Program Early Computed Tomography Scale (ASPECTS) score ≤6. A good functional outcome occurred in 813 (43.8%) patients. Independent predictors of the primary outcome, with points allocated toward the final score, included younger age, higher ASPECTS, lower NIHSS, and time from last known well to arterial puncture. The areas under the curve for derivation and validation cohorts were 0.72 (95% CI 0.70-0.75) and 0.74 (95% CI 0.71-0.80), respectively.

Discussion:
The CLEAR thrombectomy score provides a simple, validated means of predicting good functional outcome following late-window, anterior circulation thrombectomy using routinely acquired clinical and imaging data. External validation is warranted.
Abstract TP1: Changing Trends in the Epidemiology of Subarachnoid Hemorrhage: A Population-Based Study
Authors: Robinson David , Stanton Robert J , Mistry Eva , Broderick Joe , Ding Lili , Mackey Jason , Flaherty Matthew , Haverbusch Mary , Adeoye Opeolu M , Prestigiacomo Charles J , Star Michael , DeLosRiosLa Rosa Felipe , Martini Sharyl , Slavin Sabreena , Demel Stacie , Ferioli Simona , Aziz Yasmin , Walsh Kyle B , Jasne Adam S , Khatri Pooja , Woo Daniel , Kleindorfer Dawn O , Kissela Brett M
Published: February 2024

Background:
There are conflicting data on temporal trends in subarachnoid hemorrhage (SAH) incidence and outcomes. We examined trends from 1993-2020 in a long-running population-based stroke study conducted in the Greater Cincinnati Northern Kentucky (GCNK) region.

Methods:
Using a well-validated approach, we ascertained all incident nontraumatic SAHs among residents of the GCNK region in the following study periods; July 1993-June 94, calendar years 1999, 2005, 2010, 2015, and 2020. Potential cases were identified by ICD codes, abstracted, and then adjudicated by physicians. Aneurysmal SAH (aSAH) was defined as those with culprit aneurysms; cases with no available vessel imaging were considered aSAH if the hemorrhage volume was “massive” or if the patient died rapidly after onset. Incidence rates were compared over time using linear regression after normalizing to 2010 census demographics. The primary outcome assessed was unadjusted 30-day Case Fatality Rate (CFR), which was available through 2015.

Results:
We identified 518 SAH cases, of which 372 were aSAH (71.8%). Overall SAH incidence rate was stable over time, ranging from 8-10 cases per 100,000 person-years (Figure Panel A); however, the rate of aSAH showed a statistically significant decline, going from 7.2 cases/100,000 person-years in 1993 to 5.2 cases/100,000 person-years in 2020 (trend
P
=0.02). There was a nonsignificant increase in nonaneurysmal SAH (
P
=0.09 for trend). Overall 30-day CFR declined significantly through 2015 (
P
=0.006, Figure Panel B), driven predominantly by a decline in aSAH CFR (from 39.3% to 23.7%, trend
P
=0.04).

Conclusion:
We observed a significant decline in the incidence of aSAH from 1993-2020; however, overall SAH incidence was stable in the setting of numerically more nonaneurysmal SAHs. Further study is needed to understand the causes of this trend. 30-Day CFR has significantly improved both for overall SAH and for aSAH.
Abstract TP102: Pre-Hospital Obtention of Vital Information for Decision Enforcement in Cerebrovascular Emergencies: The PROVIDENCE Study
Authors: Montalvan Victor , Neves Gabriel , Shannon Jack , Kahathuduwa Chanaka , Tan Yuanyuan , Hendley Katie , Barnes Robert , Chintakayala Ayushi , Hancock Sarah , Kopel jonathan , Brister Rorie , Curry James , Pollard Rebecca , Bhatt Nirav
Published: February 2024

Background:
Difficulties determining an acute ischemic stroke patient's eligibility for intravenous thrombolysis (IVT) treatment is a frequent cause of delays.

Objective:
To assess the effectiveness of the "PROVIDENCE" datasheet, a pre-assessment of contraindications for IVT use applied by emergency medical services personnel in the field.

Methods:
This is a quasi-experimental study to evaluate the efficacy of the PROVIDENCE datasheet used by first responders. Participants were eligible if they were over 18 years old and presented to our center from the field with stroke-like symptoms with onset within 4.5 h.

Results:
We identified 465 records and included 166 records in our final analysis (54 in the study group and 112 in the control group). Eighty-five of the 166 patients received IVT (30 in the study group patients and 55 in the control group). The PROVIDENCE datasheet showed a noticeable median improvement in corrected time by five minutes from the patient's initial presentation at the emergency department to the final decision regarding IVT eligibility (p = 0.032). Additionally, the time between the first encounter with a neurology provider and the decision regarding IVT administration saw a median improvement of six minutes (p = 0.002) for the entire sample. In the subgroup that received IVT, the PROVIDENCE datasheet decreased by seven minutes (p = 0.044) the median time between the first encounter by the neurology provider and the decision regarding the administration of IVT. All other comparisons were not significant. However, the PROVIDENCE datasheet decreased the door-to-needle time by 6.5 minutes compared to the control group.

Conclusion:
Using the PROVIDENCE datasheet, first responders can quickly identify potential contraindications for IVT treatment in patients with stroke-like symptoms. This tool expedited decision-making and led to faster IVT administration process at a comprehensive stroke center.
Abstract TP109: Quality Improvement Review and Practical Consideration of Hyperfine Portable Bedside Low-Field Magnetic Resonance Imaging in the Non-ICU Setting
Authors: Morales Jorge L , Nimjee Shahid M , Forrest Cassandra , Shujaat Mohammad , Shay James , Lee Vivien H
Published: February 2024

Introduction:
The Hyperfine portable low-field Magnetic Resonance Imaging (MRI) scanner (0.064 Tesla) was FDA approved in 2020. The use of portable low-field MRI (pMRI) has been best studied in ICU settings, although there has been interest in expanding this technology in floor level status stroke patients.

Methods:
We report our experience launching pMRI in our academic comprehensive stroke program in the non-ICU setting. From September 2021 to March 2022, 24 pMRI scans were performed (2 volunteers, 22 floor-status stroke patients). Our institutional pMRI protocol includes localizer, DWI, ADC, and FLAIR (24 minutes scan time). Good head position (GHP) was defined as the vertex of the head abutting the top of the helmet insert. Complete scans were defined as including all sequences and Partial scan included DWI/ADC.

Results:
Among 24 scans, most 17/24 (70.8%) were Complete and 2 scans were aborted after only localizer images. Six scans were Partial, due to patient discomfort in 4 (“feeling hot” [2], neck/back pain [2]), and technical issues with machine in 2. Among 22 scans that were Partial or Complete, 6 scans had poor head positioning. We noted that although there was initial GHP, the head could shift out due to gravity or patient self-adjustment due to discomfort. To combat the shift issue, the bed was placed in slight reverse Trendelenburg. We also implemented wedge padding for the lower back that improved comfort. After scan # 11, re-training was performed to include GHP updates. Before re-training, 6/11 (45.5%) had GHP, and afterwards, 11/11 (100%) had GHP. Our quality review also noted that artifact on the DWI/ADC mimicking restricted diffusion could be seen in the internal capsule and corpus callosum, and clinical teams were educated on this.

Conclusions:
The use of low-field pMRI in non-ICU settings is feasible. Our institutional QI experience suggests that patient selection and technical skill in GHP is a consideration. After adjusting our protocol, the rate of GHP increased from 45% to 100%. Clinical teams also need to be aware of artifact mimicking restricted diffusion in areas of tightly bound white matter tracks. Further studies are warranted to better maximize pMRI and understand the logistical barriers to successful implementation.
Abstract TP112: Clinical Consequences of Tenecteplase Substitution for Alteplase at a Large Hub-Spoke Care Model
Authors: Sternberg Shannon , Morgan Brandy D , Jackson Cameka , Marshburn Melissa , Davis Emily , Hanna Joseph P
Published: February 2024

Introduction:
Tenecteplase (TNK) is becoming the preferred thrombolytic for acute brain ischemia. We report a system-wide transition using intentional change management of a hub-spoke delivery model annually providing about 300 intravenous thrombolytic administrations to 3000 stroke alerts from alteplase to TNK.

Methods:
By 2021, evidence supported transition to TNK from alteplase to treat acute ischemic stroke at 0.25mg/kg (maximum 25mg). We began by gathering opinions from key stakeholders regarding TNK’s clinical merit to gauge support. We subsequently educated constituents including nursing, pharmacy, technical and clinical staff. A six-month lead-in, six-month introductory, and one-year transition period began in April 2021 using an intentional change method. Median door-to-needle (DTN), door-to-puncture (DTP), thrombolytic utilization and symptomatic hemorrhage rates were recorded at five primary (P) and a comprehensive stroke center (C).

Results:
During lead-in to TNK, DTN were 60(P), 26(C) minutes with 10%(P), 19%(C) utilization. DTP was 73 minutes. Symptomatic hemorrhage occurred in 0.0%(P), 4.9%(C) of alteplase-treated patients. During TNK’s 6-month introductory period DTN were 60(P), 20(C) minutes with 10%(P), 19%(C) utilization. DTP was 71 minutes. Symptomatic hemorrhage occurred in 0.0%(P), 4.9%(C) of TNK patients. During the subsequent one-year transition period, DTN was 53(P) and 23(C) minutes with 8%(P),16%(C) utilization. DTP was 78 minutes. Symptomatic hemorrhage occurred in 1.5%(P) and 3.0%(C).

Conclusions:
Hub-spoke delivery systems can safely transition to TNK using intentional process change reducing DTN and hemorrhagic complications with stable utilization. Substitution may not reduce DTP if thrombolytic administration is not the rate-limiting step. Intentional process change provides smooth transition when stakeholder education precedes, and pathway adherence follows implementation.
Abstract TP116: Impacts of Formal Clinical Trial Didactic Training for Vascular Neurology Fellows
Authors: Stalin Karen , Staugaitis Abbey , Silva Luis , Streib Christopher D
Published: February 2024

Introduction:
A key barrier to stroke clinical trial recruitment is the lack of experienced investigators at the site level. However, there are currently no standards for training Vascular Neurology Fellows in clinical trial recruitment. We studied the impact of a formal clinical trial didactic curriculum on stroke fellows.

Methods:
Our institution initiated clinical trial training for Vascular Neurology Fellows in 2016 with the curriculum expanding year upon year (Figure 1a). We reviewed all clinical trial enrollments from 2015-2022 and determined the number completed by stroke fellows. The proportion of fellow enrollments was analyzed using the Mann-Kendall test. We surveyed past fellows to obtain their feedback on the clinical trial training curriculum and determine whether they were actively participating in clinical trials or planned to do so in the future.

Results:
Fourteen of sixteen (87.5%) past fellows completed the survey. Figure 1b shows fellow enrollment and total enrollments by academic year. The Mann-Kendall test demonstrated a trend for an increasing proportion of fellow enrollments during the study period (p=0.08). Seven past fellows (50%) are currently enrolling in clinical trials; four of whom (57.1%) enrolled greater than or equal to three subjects during fellowship. Thirteen (92.8%) intend to enroll in clinical trials in the future. Past fellows stated that the most valuable aspect of their clinical trial training was learning how an enrollment works and obtaining an informed consent.

Conclusion:
Our results show that a clinical trial didactic curriculum during Vascular Neurology Fellowship might increase clinical trial recruitment by fellows. Furthermore, engagement in clinical trial training and recruitment during fellowship was suggestive of continued engagement in future practice.
Abstract TP119: Predicting Posterior Circulation Stroke During Emergency Triage: Dizzy-7 Project
Authors: Fazzio Corinna , Ashley Kevin , Yee Alan H
Published: February 2024

Introduction:
“Stroke code” activation is a uniform process to summon healthcare stakeholders to orchestrate the rapid sequential steps for urgent management in patients with possible stroke. Acute dizziness, a common emergency department (ED) presentation, frequently leads to stroke code activation; however, cancellation rates remain high and process improvement strategies are warranted.

Methods:
We analyzed stroke identification accuracy, cancellation rates, and clinical characteristics in patients presenting with an acute vestibular syndrome to inform process improvement strategies for stroke code activation. We developed an ED triage diagnostic algorithm termed, “Dizzy-7”, based on evidence incorporating key history and physical examination elements derived in patients with acute posterior circulation ischemia. Subsequent analyses were performed on algorithmic utilization and its ability to predict stroke.

Results:
1599 patients presented with acute dizziness over a 4-month period (2022-2023). Stroke code activation occurred in nearly one in four (366/1599) these presentations. 20% (319/1599) were ultimately diagnosed with stroke and of these, 49% (319/366) were identified following stroke code activation. The Dizzy-7 algorithm was used infrequently (4%) among all acute dizziness presentations. Of the 65 cases that incorporated the algorithm, 16 resultant stroke code activations occurred with 1 confirmed diagnosis (6%). We analyzed stroke alert cancellation and found an increased frequency in cancellation for those without use of the protocol at 22% (77/350) compared to those who did use it at 6% (1/16).

Discussion:
Accurate and reliable identification of acute ischemic stroke among patients presenting with acute dizziness remains complex. Implementation of a triage diagnostic algorithm based on contemporary evidence was infrequently implemented. Process improvement efforts targeted at greater algorithmic use, interprofessional collaboration, and education may improve stroke code utilization efficiency. Although based on limited sample size, a trend towards reduced stroke code cancellation rates were seen throughout the pilot Dizzy-7 algorithm use.