bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 121: Prospective Symptomatic Hemorrhage Rates And Functional Outcomes In Trial Eligible Cavernous Angiomas With Symptomatic Hemorrhage
Authors: Flemming Kelly , Mandrekar Jay , Harmsen William , Kim Helen , Nelson Jeffrey , Lanzino Giuseppe S , Huang Judy , Hanley Dan , Stadnik Agnieszka , Torbey Michel T , Thompson Richard , Treine Kevin , Awad Issam A
Published: February 2023

Background:
Cerebral cavernous angiomas with symptomatic hemorrhage (CASH) carry highest rebleed rates and are targeted for novel interventions. A multisite clinical trial readiness project (clinicaltrials.gov NCT03652181) aims to identify clinical and functional changes over time in trial eligible CASH patients.

Methods:
Adult patients from 5 high volume centers with a CASH in the prior year and no planned surgical intervention were enrolled. In addition to demographic, clinical, and imaging review, patients underwent baseline, 1 year and 2 year NIH-stroke scale (NIHSS), modified Rankin scale (mRS), Euro-QOL 5D-3L (EQ-5D-3L) and EQ VAS (visual analog score), and PROMIS 29 assessments. Recurrent symptomatic hemorrhages (SH) were verified. We assessed the hemorrhage rate, change in scores/scales over time, and determined which scales/scores were most affected in patients with SH.

Results:
123 patients completed baseline assessments and were prospectively followed (60.9% female; mean age 44.1 years; 39.1% familial; 41.5% brainstem location). As of reporting date, 89 of 104 (86%) and 58 of 76 (76%) cases have completed assessments. There were 16 SHs during 147 patient-years of follow up (10.9% per patient year). At baseline, 111 (90.2%) of patients had NIHSS 0-2 and 77 (62.6%) patients had mRS baseline 0-1 which improved to 40 (95.2 %) and 43 (75.4%) at 2 years. At baseline, 54 (43.9%) of patients had at least one moderate to severely abnormal PROMIS-29 domain compared to 13 (26.5%) at 2 years. EQ-5D-3L baseline demonstrated a moderate proportion of patients reporting some difficulty with pain (48.8%), anxiety (41.5%), and activity (41.5%) which improved to 28%, 30%, and 34% respectively at 2 years. Patients with a prospective SH were more likely than those without recurrent SH at 2 years to display mild functional decline (0.5 SD) of most PROMIS-29 domains, a mRS of 2 or higher and an abnormal EQ- self-care (P<0.05). Other scales/scores were not significantly different between the groups.

Conclusion:
We report SH rate and functional outcome at baseline and rates of changes during 2 years in trial eligible CASH patients. The PROMIS-29, mRS, and EQ-self-care domains were most discriminative in patients with recurrent SH. No test was 100% specific.
Abstract 123: In Vivo Permeability Of The Aging Brain With Cerebral Microbleeds
Authors: Romanos Sharbel , Srinath Abhinav , Li Ying , Chen Chang , Bindal Akash , Debiasse Dorothy , Dimov Alexey , Moore Thomas , Lightle Rhonda , Stadnik Agnieszka , Carroll Timothy , Girard Romuald , Awad Issam A
Published: February 2023

Introduction:
Age-related cerebral microbleeds (CMBs) are vascular changes associated with an increased risk of intracerebral hemorrhage (ICH) and neurocognitive decline. CMBs share a strikingly similar appearance on MRI to cerebral cavernous malformations (CCMs), which are leaky capillary lesions predisposing patients to brain bleeding. Our team had previously shown increased vascular permeability in CCM and in the brain of older subjects, with common circulating biomarkers of angiogenesis and inflammation. We examine here whether vascular permeability is greater in the aging brain harboring CBMs.

Methods:
Dynamic Contrast-Enhanced Quantitative Perfusion (DCEQP) MRI, which assesses vascular permeability, was acquired for 7 patients with CMBs (>50 years old), 10 old (>50 years old), and 9 young (18-30 years old) healthy subjects without CMBs. Cases with active brain disease, stroke or seizure in the prior year were excluded. DCEQP scans were co-registered onto their respective T1-weighted images, normalized using the Desikan-Killiany atlas, and finally segmented into white and gray matter within frontal, temporal, parietal, and occipital lobes. The mean permeability was calculated within each segmented area, and values were compared between the 3 groups of interest.

Results:
Increased permeability was observed within the frontal white and gray matter as well as the parietal gray matter of patients with CMBs compared to age matched old healthy controls (both: p<0.05). In addition, greater background brain permeability was also observed in old healthy controls compared to young healthy controls, in the occipital white matter, as well as the white and gray matter in the temporal and parietal lobes (all: p<0.05).

Conclusion:
We confirm that the human brain exhibits increased vascular permeability with aging, and this is more pronounced in brains harboring CMBs. This may provide insight into the pathogenesis of CMBs, potentially reflecting end stage age-related failure of the blood brain barrier, associated with frank bleeding. These results offer a starting point for the development of diagnostic and prognostic imaging biomarkers of CMBs, which can help stratify patients at higher risk of future ICH and cognitive decline.
Abstract 124: Circulating Expression Signatures Can Predict Intracranial Aneurysm Growth As Assessed By The Predicted Aneurysm Trajectory Score
Authors: Poppenberg Kerry , Chien Aichi , Waqas Muhammad , Monteiro Andre , Burkhardt Jan-Karl , Mokin Maxim , Siddiqui Adnan H , Tutino Vincent
Published: February 2023

Background:
Intracranial aneurysm (IA) rupture is associated with high morbidity and mortality rates. Identifying unstable, growing IAs can enable critical treatment before rupture.

Hypothesis:
RNA expression profiles in whole blood are different among cases of growing vs. stable IA, and thus may be candidate risk assessment biomarkers.

Methods:
We performed RNA sequencing on 69 blood samples from IA patients. To assess if IAs would grow or not, we calculated the published Predicted Aneurysm Trajectory (PAT) score. We dichotomized samples into stable and growing IAs by median PAT. Combat-seq removed potential batch effects and counts were normalized to TPMs. After randomly dividing the dataset into a training and testing cohort, differentially expressed (protein-coding) genes (DEGs) in the training dataset were defined as those with an FDR-corrected F-test (
q
-value)<0.05, an absolute fold-change≥2, and expression (TPM>0) in at least 50% of the samples. A Gaussian Naïve Bayes (GNB) model using the DEGs was trained and independently tested. To understand the pathobiology associated with the DEGs we performed gene ontology term enrichment analysis.

Results:
The PAT score predicted 34 IAs to be stable and 35 to be growing. Between these groups, we identified 36 DEGs that discriminated growing from stable IAs (Figure, A and B). Our GNB model using the DEGs achieved 86% accuracy in training (Figure, C). In the testing cohort, the DEGs also delineated growing from stable IAs (Figure, D), and the model had 70% accuracy (Figure, E). DEGs with increased expression in growing IAs were enriched for biological process (BP) terms including neutrophil activation and degranulation, while DEGs decreased in growing IAs were enriched for BP that included NK-cell immunity and cytotoxicity (Figure, F).

Conclusion:
Circulating transcriptomes can delineate IA growth based on the PAT score. Our biomarker model must be validated in larger cohorts and evaluated in longitudinal datasets.
Abstract 125: Enlarged Perivascular Spaces In The Centrum Semiovale Are Associated With Incident Late-life Depression: Framingham Heart Study
Authors: Medved Sara , Pinheiro Adlin , parva pedram , Himali Jayandra J , Seshadri Sudha , Demissie Serkalem , Romero Jose R
Published: February 2023

Introduction:
Perivascular spaces visible on brain MRI (PVS) are considered cerebral small vessel disease (CSVD) markers, possibly reflecting impaired brain fluid and metabolite clearance, and could contribute to depression in old age. This study aims to determine the association of PVS with prevalent and incident depression in the community-based Framingham Heart Study (FHS).

Methods:
FHS participants free of stroke and dementia with available Center for Epidemiological Studies Depression (CES-D) scale and PVS ratings in the basal ganglia (BG) and centrum semiovale (CSO) were included. Depression was defined as CES-D score≥16 or use of antidepressants. PVS were rated on a scale from I-IV in the BG and CSO using a validated method, with grades III-IV representing high PVS burden. A mixed score was created to describe high burden in the BG and/or CSO (0=no high ePVS burden, 1=high burden in the BG, 2=high burden in the CSO, 3=high burden in both regions). Logistic regression analysis was used to assess the association between PVS in the CSO, BG, and mixed regions and prevalent and incident depression. Models adjusted for age, sex, FSH cohort, time interval between CES-D score and MRI measurements, body mass index, smoking status, prevalent hypertension and diabetes.

Results:
Among 3815 participants included (mean age 57±14, male 47%), incident depression was observed in 19% over the follow up period ranging from 8 to 15 years subsequent to PVS rating. In multivariable adjusted analyses, high burden PVS in the CSO was associated with incident depression (OR 1.75 [1.18, 2.60], p=0.005). In the mixed score, concurrent high burden PVS in both regions (OR 2.10 [1.13, 3.91], p=0.02) and high burden in the CSO only (OR 1.65 [1.05, 2.58], p=0.03) were associated with incident depression. PVS were not associated with prevalent depression.

Conclusion:
In conclusion, high PVS burden was associated with incident depression in a community-based sample free of stroke and dementia. The association was predominantly driven by high burden of CSO PVS, suggesting that lobar forms of CSVD may play role in late life depression, possibly reflecting disrupted neuroanatomic circuits involved in mood control, and differing from BG PVS.
Abstract 126: Genetic Analyses Of Oral Health And Neuroimaging Markers Of Brain Health In Persons Without Stroke
Authors: Rivier Cyprien , Renedo Daniela , De Havenon Adam H , Payabvash Sam , Sheth Kevin N , Falcone Guido J
Published: February 2023

Background:
Oral health is a modifiable risk factor for stroke. However, the role of oral health in the brain health of clinically asymptomatic persons remains understudied. We hypothesize that genetically-determined poor oral health leads to worse neuroimaging brain health profiles in persons without stroke.

Methods:
We conducted a two-sample Mendelian Randomization (MR) study. As instruments, we used 105 genetic variants known to be associated (p<5x10
-8
) with a composite of caries, dentures and missing teeth in the GLIDE Consortium. In stroke-free participants enrolled in the UK Biobank, we tested for association between these genetic variants and white matter hyperintensity volume (natural log-transformed), fraction anisotropy and mean diffusivity. For the last two neuroimaging traits, we evaluated the first principal component of measurements obtained across 48 brain regions.

Results:
Our primary analysis using the inverse variance-weighted MR method indicated that genetically-increased risk of poor oral health was associated with: (1) higher burden of silent cerebrovascular disease, as represented by higher volumes of white matter hyperintensities (beta=0.24, SE=0.07 p-value=0.001), and (2) increased microstructural damage, as represented by lower fractional anisotropy (beta=-2.53, SE=0.38; p=1x10
-9
) and higher mean diffusivity (beta=3.42, SE=0.41; p=2x10
-11
). Sensitivity analyses identified horizontal pleiotropy in our primary results, but an outlier-corrected analysis confirmed all three initial results (all p-values <0.001, Table 1).

Conclusion:
Among persons without stroke, genetically-determined poor oral health is associated with worse neuroimaging brain health profiles. Because gene-disease associations are immune to confounding, our results indicate that this association is causal. Early treatment of poor oral health may lead to significant brain health benefits, even in persons without stroke.
Abstract 133: Over Estimation Of Percent Stenosis By Physician Operators May Lead To Carotid Stent Over Utilization
Authors: Jareczek Francis , FARRELL Mary B , Lehman Erik , Sila Cathy A , Terry John , SACKS DAVID , Kalapos Paul , Simon Scott , Cockroft Kevin M
Published: February 2023

Introduction:
Based largely on the inclusion criteria of clinical trials, the degree of cervical carotid artery stenosis is often used as an indication for stent placement in the setting of carotid atherosclerotic disease. However, the rigor and consistency with which such stenosis is measured outside of clinical trials is unclear. We compared the percent stenosis as measured by real world physician operators to that measured by independent expert reviewers.

Hypothesis:
We hypothesized that the documented degree of stenosis, termed operator-reported stenosis (ORS), from real world facilities performing carotid stent placement would be larger than the reviewer-measured stenosis (RMS) as assessed by clinicians experienced in treating carotid artery disease.

Methods:
Images were selected from patient cases used for carotid stenting facility accreditation. Data collected included demographics, National Institutes of Health Stroke Scale, modified Rankin Score, and the documented degree of stenosis (ORS). The ORS was compared to the RMS, derived from a panel of expert clinicians.

Results:
A total of 68 angiograms were reviewed from 39 symptomatic and 29 asymptomatic patients. The RMS values demonstrated excellent agreement with an intra-class correlation of 0.80. The median ORS was 90.0% (IQR 80.0, 90.0) versus a median RMS of 61.1% (IQR 49.8, 73.6), with a median difference of 21.8% (IQR 13.7, 34.4),
p
< 0.001. This discrepancy persisted within several subpopulations and was larger among asymptomatic patients and those treated at facilities granted delayed accreditation. Based on RMS values, 72% of symptomatic patients and only 10% of asymptomatic patients would meet the Centers for Medicare and Medicaid Services criteria for carotid stent placement.

Conclusions:
Real world operators tend to overestimate cervical carotid artery stenosis compared to external expert reviewers. Since decisions regarding carotid revascularization are often based at least partially on percent stenosis, such measuring discrepancies inevitably lead to a higher volume of procedures, which may in turn represent a degree of procedural over utilization.
Abstract 139: Depression Following Small Vessel Stroke Is Common And More Prevalent In Women
Authors: Dymm Braydon , Goldstein Larry B , El Husseini Nada K , Bushnell Cheryl D , Koltai Deborah
Published: February 2023

Background:
Post-stroke depression (PSD) affects about one third of stroke survivors and is associated with poorer quality of life. Little is known about the prevalence and independent risk factors for depression associated with small vessel stroke (SVS).

Methods:
We conducted a retrospective analysis of a prospective cohort of patients enrolled in the American Stroke Association-Bugher SVS Study, which enrolled 200 patients within 2 years of SVS and 79 controls without stroke history from 2007 to 2012 at four clinical sites. The primary outcome was PHQ-8 dichotomized at (≥10 and <10) with higher scores consistent with PSD. Chi-square test was used to compare the rates of depression between the two groups. Logistic regression was used to evaluate factors associated with depression in patients with SVS adjusted for age, sex, race/ethnicity, NIH Stroke Scale, white matter disease (WMD) burden, Montreal Cognitive Assessment short-form score, and history of diabetes.

Results:
The cohort included 161 participants with SVS (excluding 39 due to missing key variables) and 79 controls. Participant characteristics are described in Table 1. The mean time between stroke and depression screening was 74 days. Among participants with SVS, 31.7% (n=51) screened positive for PSD, compared to 6.3% (n=5) of controls, OR= 6.9 (95%CI 2.6-18.0%; p<0.0001). PSD was prevalent in 35.9% of participants with SVS who had good functional outcome (modified Rankin score ≤2). Female sex was the only variable associated with PSD in those with SVS (OR 2.3, 95%CI 1.0-5.2, p=0.041).

Conclusion:
In this well-characterized cohort of SVS with mostly mild stroke severity, depression within 3 months of the incident stroke was about 7 times more likely than those without a history of stroke. The extent of WMD was not associated with PSD, suggesting that small vessel disease other than the incident SVS does not account for the increased rates of PSD. Depression following SVS was more prevalent in women.
Abstract 143: Sepsis And Risk Of Major Postoperative Vascular Complications
Authors: Reish Nicholas J , Batra Ayush , Odell David D , Maas Matthew B
Published: February 2023

Introduction:
Stroke, myocardial infarction (MI), and pulmonary embolism (PE) greatly increase postoperative morbidity and mortality. Sepsis has been linked to increased risk of major vascular events, but the risk related to sepsis exposure throughout the postoperative period is uncertain.

Hypothesis:
Perioperative sepsis exposure increases the 30-day risk of postoperative stroke, myocardial infarction (MI), and pulmonary embolism (PE).

Methods:
Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), a formulaic sampling of surgical cases from participating United States institutions that prospectively collects demographic, clinical, surgical and 30-day outcome data. Sepsis was defined by systemic inflammatory response syndrome with either positive blood culture or evidence for infection found intraoperatively, and severe sepsis/shock as sepsis with evidence of organ dysfunction or circulatory dysfunction. We used mixed-effects Cox proportional hazard models, treating type of surgery as a random effect, to estimate the hazard ratios for major vascular complications due to sepsis and severe sepsis/shock exposure, adjusting for otherrisk factors.

Results:
We studied 6,614,937 surgical procedures. There were 201,230 cases with sepsis and an additional 78,052 cases of severe sepsis/shock. Outcomes included 13,939 strokes, 23,600 MIs, 21,893 PEs, and 1690 cases with multiple major vascular complications. Exposure to sepsis (HR 1.98, 95% confidence interval 1.91 to 2.06) or severe sepsis/shock (HR 3.27, 3.14 to 3.40) increased the risk of major vascular complications with larger effect than other established risks. Sepsis improvement within the preoperative period was associated with reduced risk (HR 0.82, 0.77 to 0.88). These findings were consistent in separate models for each complication.

Conclusions:
Sepsis approximately doubles and severe sepsis or shock triples the 30-day postoperative risk of major vascular complications. Improvement in sepsis severity prior to operation is associated with a 20% risk reduction.
Abstract 145: Dietary Intake And Quality Among Stroke Survivors Compared To Matched Controls Who Participated In The National Health And Nutrition Examination Survey: 1999 - 2018
Authors: Zoellner Erika R , Patterson Mindy A , Sharrief Anjail Z , Savitz Sean I , Tucker Wesley J , Miketinas Derek C
Published: February 2023

Introduction:
Nutrition is an important modifiable risk factor for the prevention and treatment of stroke. However, the examination of nutrient intake and diet quality in stroke survivors is limited. The purpose of this study was to estimate usual nutrient intake and diet quality in a nationally representative sample of US adults who have a history of stroke and compare to controls.

Methods:
National Health and Nutrition Examination Survey 1999-2018 data were used to examine 1,626 stroke survivors matched for age, gender, and survey cycle to their respective controls (n=1,621), with no history of stroke. Data were collected on demographics and dietary intake and quality (assessed by Healthy Eating Index [HEI] 2015) from at least one reliable 24-h dietary recall. Estimates were reported as mean[SE]. Differences in continuous and categorical variables were assessed using independent-samples t-tests and Rao-Scott Chi-Squared tests, respectively.

Results:
In comparison to controls, stroke survivors were more likely to report excessive (% > Acceptable Macronutrient Distribution Range) intake for total fat (50.9%[2.7] vs. 40.4%[2.2], p<.001), and inadequate intake (% < Estimated Average Requirement) for calcium (54.6%[1.8] vs. 43.5%[2.4], p=.001) and magnesium (66%[1.8] vs. 53.6%[1.8], p<.001). In addition, stroke survivors were less likely to report adequate intakes (% > Adequate Intake) for fiber (6.8%[0.9] vs. 11.9%[1.3]) and potassium (0.8%[0.3] vs. 1.0%[0.4]) (p<.001, all comparisons). Finally, stroke survivors reported lower HEI scores than controls (49.8 vs. 51.9, p<.001) which indicates lower diet quality, and were more likely to be food insecure, and report physical and mental limitations including difficulty preparing and eating meals compared to controls (p<.001, all comparisons).

Conclusions:
Stroke survivors had lower overall diet quality and greater prevalence of inadequate nutrient intake profiles typically associated with increased risk of cardiovascular diseases including higher total fat intake and lower intake of key micronutrients and fiber compared to matched controls. Stroke survivors were also more likely to experience food insecurity and have physical and mental limitations that may directly impact dietary intake.
Abstract 151: Genetic Factors And Outcomes After Stroke: A Preliminary Analysis Of The Strong Study
Authors: Cramer Steven C , Parodi Livia , Rosand Jonathan , Holman Alison ,   the STRONG Study Investigators
Published: February 2023

Introduction:
Measures of genetic variation have provided insight into underlying biology and treatment approaches in a number of medical sciences. The STRONG (“The Stroke, sTress, RehabilitatiON, and Genetics Study”) Study evaluated genetic polymorphisms in relation to stroke recovery.

Methods:
The STRONG Study recruited patients with a new stroke from 28 U.S. stroke centers. Entry criteria included age ≥18 years and new ischemic stroke or intracerebral hemorrhage. Visit 1 was during acute admission; Visit 2, 90 days post-stroke; Visit 3, 6 mo post-stroke; and Visit 4, 12 mo post-stroke. Linear regression examined specific genotypes in relation to 2 primary outcomes (change in grip force from V1-V2 and global function (SIS-ADL) at V2) and 2 secondary outcomes (depression (PHQ-8) at V2 and cognitive function (t-MoCA) at V4). No correction for multiple comparisons is made below.

Results:
There were 763 patients enrolled from 2016-2020, with mean age 63.1±14.9 years, 41.1% female, median NIHSS score 4 [2-9]. Data were available in 510 patients at Visit 2 and 482 at Visit 4. The BDNF val66met polymorphism (rs6265) was related to poorer V4 MoCA score (p=0.01). Presence of ApoE4 was not related to any endpoint. For the dopamine polygene score, a relationship with lower score (reduced dopamine neurotransmission) and greater depression (higher V2 PHQ-8 score) was suggested (p=0.1). A polymorphism (rs1842681) associated with chronic mRS score in a prior GWAS study (Neurology. 2019;92:e1271) was related to STRONG Study d90 mRS score (p=0.05). Three polymorphisms (rs76221407, rs150862264, rs182008837) associated with 3-mo mRS score in a separate GWAS study (Circ Res. 2019;124:114) were not related to STRONG Study d90 mRS score (p=.71-.78).

ConclusionS:
The STRONG Study collected genotypes and detailed longitudinal behavioral data during the year following stroke. Data do not support several hypotheses. However, presence of the BDNF val66met polymorphism may be related to poorer cognitive outcome. Lower dopamine gene score showed a trend with greater depression, consistent with a prior publication. Current findings support a prior GWAS finding for chronic mRS score. Genetics studies provide insights into inter-subject differences in recovery after stroke.
Abstract 153: Use Of Patient-reported Outcome Measures (PROMS) In The Primary Publications Of Acute Stroke Clinical Trials (2010-2020)
Authors: Hostnik Joseph , Strong Brent , Reeves Mathew J
Published: February 2023

Background:
Patient-reported outcome measures (PROMs) describe health status from the perspective of the patient. There is growing interest in the use of PROMs in clinical trials and there have been major efforts to develop PROMs for neurological conditions (e.g., Neuro-QOL, PROMIS). However, the extent to which such measures are used in stroke trials is uncertain. We sought to determine how often contemporary acute stroke trials included PROMs as primary or secondary outcome measures.

Methods:
We searched MEDLINE for completed RCTs published in one of nine major journals between 2010 and 2020. Eligible studies were phase 2 or 3 trials undertaken to test therapeutic interventions within one month of stroke onset. For each trial we accessed the primary publication as well as the published protocol and supplement when available. We abstracted key trial characteristics including all primary and secondary efficacy outcome measures. We defined PROMs using online databases (qolid.org) with the focus on self-reported measures of quality of life, symptoms, and function collected without interpretation of an external party.

Results:
115 trials met eligibility criteria. Only one trial used a PROM for its primary outcome measure (visual analogue pain scale), but 40 trials (35%) listed at least one PROM as a secondary outcome measure in its primary publication. An additional 15 trials (13%) listed at least one PROM in their protocol. Among the 55 trials that defined at least one PROM as a secondary outcome measure, the most commonly used measure was Euro-QOL (n=42, 76%) followed by SIS-16 (n=9, 16%), SF-36 (n=7, 13%), and the stroke-specific QOL scale (n=5, 9%). Other PROMs included various measures of anxiety and depression (n=9, 16%). Only one study used a Neuro-QOL based measure. Of the 41 trials that listed a PROM as a primary or secondary outcome in the primary publication, 39 (95%) provided PROM results, but of these only 7 (18%) found statistically significant treatment differences.

Conclusions:
While about half of acute stroke trials listed at least one PROM as a secondary outcome, they played a minor role in the presentation of trial results. Inclusion of PROMs in acute stroke trials requires greater attention during both the design and reporting phases of the trial.
Abstract 157: Association Of Hospital Performance With 1-Year Mortality And Recurrence After Ischemic Stroke Among US Medicare Beneficiaries
Authors: Leifheit Erica C , Wang Yun , Goldstein Larry B , Lichtman Judith H
Published: February 2023

Background:
Whether stroke patients treated at hospitals with better short-term quality performance metrics have better long-term outcomes is unknown. We determined if ischemic stroke patients treated at US hospitals with better past performance on the Centers for Medicare & Medicaid Services (CMS) 30-day mortality and readmission outcome measures for stroke had better 1-year outcomes compared to those treated at other hospitals.

Methods:
We included all Medicare fee-for-service beneficiaries aged ≥65 years discharged alive from US hospitals with a principal diagnosis of ischemic stroke from 07/01/2015 to 12/31/2018. We categorized patients by the treating hospital’s performance on the CMS hospital-specific 30-day risk-standardized all-cause mortality and readmission rate measures for stroke from 07/01/2012 to 06/30/2015: Low-Low (both CMS mortality and readmission rates for the hospital were <25
th
percentile of national rates), High-High (both >75
th
percentile), and Intermediate (all others). We balanced characteristics between hospital performance categories using stabilized inverse probability weights (IPW) based on patient demographic and clinical factors. We fit Cox models to assess patient risks of 1-year mortality and recurrent stroke across hospital performance categories, weighted by the IPW and accounting for competing risks.

Results:
There were 595,929 stroke patients (mean age 78.9y, 54.4% women, 82.2% White) discharged from 134 Low-Low, 2288 Intermediate, and 141 High-High hospitals. For patients treated at Low-Low, Intermediate, and High-High hospitals, respectively, 1-year mortality rates were 23.8% (95% CI 23.3-24.3%), 25.2% (25.1-25.3%), and 26.5% (26.1-26.9%), and recurrence rates were 8.0% (7.6-8.3%), 7.9% (7.8-8.0%), and 8.0% (7.7-8.3%). Compared with patients at High-High hospitals, those at Low-Low and Intermediate hospitals, respectively, had 15% (hazard ratio 0.85; 95% CI 0.82-0.87) and 9% (0.91; 0.89-0.93) lower risks of 1-year mortality but no difference in 1-year recurrence.

Conclusions:
Ischemic stroke patients treated at better-performing hospitals had lower risks of post-discharge 1-year mortality but similar risks of recurrent stroke compared with patients treated at other hospitals.
Abstract 162: Molecular And Microstructural Alterations In Cerebral Amyloid Angiopathy-related Hemorrhagic Manifestations
Authors: Gokcal Elif , Becker J Alex , Horn Mitchell J , Das Alvin S , Abramovitz Fouks Avia , Schwab Kristin , Biffi Alessandro , Rosand Jonathan , Viswanathan Anand , Polimeni Jonathan , Johnson Keith A , Greenberg Steven M , Gurol Edip M
Published: February 2023

Background and Purpose:
We aimed to compare the amyloid load and degree of microstructural injury among Cerebral Amyloid Angiopathy (CAA) patients with either higher lobar cerebral microbleed (CMB) counts or higher cortical superficial siderosis (cSS) extent against CAA patients with lower hemorrhagic load.

Methods:
The study included 38 cognitively healthy probable CAA patients with lobar intracerebral hemorrhage (ICH) and 38 age, sex-matched healthy controls (HC) who underwent advanced MRI, and Pittsburgh Compound B (PiB) PET scans. Patients were categorized into CMB-Dominant (CMB-D) and cSS-Dominant (cSS-D) based on the number and extent of CMB and cSS using previously identified cutoffs (Figure). The mean global cortical amyloid load was calculated from PiB-PET scans and represented by PiB-DVR. Within the CAA cohort, the Peak Width of Skeletonized Mean Diffusivity (PSMD) was calculated from diffusion MRIs and used as a marker of microstructural integrity.

Results:
Patients with CAA had significantly higher PiB-DVR than HCs (1.40±0.24 vs. 1.19±0.22, p<0.001). Both CMB-D and cSS-D CAA patients had significantly higher amyloid and increased (worse) PSMD compared to CAA patients with a non-dominant low hemorrhagic load (Figure). These results did not change in separate regression models corrected for age and sex. PiB-DVR significantly correlated with increased PSMD (r=0.346, p=0.033).

Conclusions:
Our findings support the view that vascular amyloid load drives higher CMB counts, more extensive cSS, and microstructural injury in patients with CAA. Furthermore, the correlations among these markers suggest that these MRI-based categorizations (CMB-D and cSS-D patients) can be used for disease staging and further research.
Abstract 17: Ultra-early Activation Of Neuroinflammatory Cascade Following Acute Stroke: Plasma And Extracellular Vesicle Biomarkers From A Mobile Stroke Unit
Authors: Kowalski Robert , Ledreux Aurelie , Violette John E , Neumann Robert T , Grotta James C , Ornelas David , Yu Xiaoli , Griffiths Steven G , Lewis Scott , Nash Priscilla , Monte Andrew A , Coughlan Christina M , Deighan Clayton , Jones William J , Graner Michael W
Published: February 2023

Background:
Neuroinflammation is ubiquitous in acute stroke and worsens outcome. However, the precise timing of the inflammatory response is unknown, hindering the design of acute anti-inflammatory therapeutic interventions. We used a mobile stroke unit (MSU) to identify the onset of the neuroinflammatory cascade within minutes of symptom onset.

Methods:
The study is a prospective, cohort investigation of ultra-early blood- and extracellular vesicle (EV)-derived markers of neuroinflammation and outcome in acute stroke. Blood was obtained on the MSU with head CT, and from healthy controls. Plasma biomarkers were analyzed with ELISA, SIMOA and ECL. EVs were isolated with HSP pull down. Confirmed strokes, mimics and healthy controls were compared. Variables included demographics, mRS, NIHSS and discharge disposition.

Results:
Forty one adults were analyzed, including 15 patients treated on the MSU between August 2021 and April 2022, and 26 controls. For MSU patients, median age was 74 (range 36-97) years, 60% were female, and 80% white. Ten (67%) were diagnosed as stroke, with 8 (53%) confirmed and 2 likely TIA or stroke averted by thrombolysis; 5 were stroke mimics. For strokes, median initial NIHSS score was 11 (range 4-19) and 6 (75%) received tPA. Blood was obtained a median of 58 (range 36-133) minutes after symptom onset. Within 36 minutes after stroke, plasma interleukin-6 (IL-6), neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were elevated by as much as 10 times normal. In EVs, matrix metalloproteinase-9 (MMP-9), chemokine (C-X-C motif) ligand 4 (CXCL4), C-reactive protein (CRP), IL-6, osteopontin (OPN) and platelet and endothelial cell adhesion molecule 1 (PECAM1) were elevated. Inflammatory markers increased rapidly in the first two hours, and continued rising for 24 hours.

Conclusions:
This study found the inflammatory cascade is activated as early as 36 minutes after stroke, and progresses rapidly. This is earlier than observed previously in humans, and suggests injury from neuroinflammation may occur faster than had been surmised. The findings may inform development of immunomodulatory therapies for acute stroke, and lead to new diagnostic tools and improved outcomes.
Abstract 19: Loss Of Endothelial Tissue-nonspecific Alkaline Phosphatase Modifies Sensorimotor Deficits In Chronic Ischemic Stroke
Authors: Clary Briana L , Beswick Cory B , Golestanian Omid , Barnes Katie M , Pacheco Pereira Bernardo , Brown Candice M
Published: February 2023

Tissue nonspecific alkaline phosphatase (TNAP) is an ectoenzyme that is known for its anti-inflammatory properties in the immune system. Although TNAP is present in nearly every cell, it is highly abundant in brain endothelial cells (BEC). However, the role of TNAP in the BECs and other cells in the neurovascular unit is poorly understood. Our laboratory has previously identified a role for BEC TNAP in vascular integrity. While the loss of cortical TNAP activity has been observed in ischemic stroke, the functional outcomes that result from the loss of the enzyme are less clear. The objective of this study is to determine how TNAP affects post-stroke functional outcomes. We hypothesized that the loss of endothelial TNAP worsens post-stroke sensorimotor deficits. To test this, we generated mice with a conditional deletion of
Alpl
, the gene that codes for TNAP, in endothelial cells (VE-cKO mice) and compared the results to their littermate controls (

Alpl
fl/fl

). Male and female six month-old mice (n=40) received a photothrombotic ischemic stroke (PTS) or sham surgery followed by daily neurological assessment (Clark’s test) and comprehensive sensorimotor testing, i.e. corner test, rotarod, open field, and gait analysis (DigiGait), over a seven-day period. Laser speckle flowmetry confirmed that PTS mice exhibited a sustained loss of cerebral blood flow compared to sham mice (p<0.0001). Daily neurological scoring showed higher (worse) scores in VEcKO PTS-mice compared to littermate controls (p=0.004). Quantification of total spontaneous movement via open field testing showed a significant interaction among stroke, genotype, and time (p=0.014). Gait analysis showed that the post-stroke stance/swing ratio, a measure of stability, differed between the left and right hind paws in VEcKO mice compared to controls: right hind paw- genotype x stroke interaction (p=0.041), and left hind paw- genotype x surgery x sex interaction (p=0.005). Significant interactions between surgery and sex were also observed in the right fore paw for stride (p=0.02), stride frequency (p=0.00026), and stride length (p=0.02). These results demonstrate a novel role for endothelial TNAP in functional recovery post-stroke.
Abstract 2: Timing And Predictors Of Recanalization After Cerebral Venous Thrombosis
Authors: Salehi Omran Setareh , Shu Liqi , Chang Allison , Parikh Neal S , Zubair Adeel , Simpkins Alexis , Heldner Mirjam , Hakim Arsany , Al Kasab Sami , Nguyen Thanh , Klein Piers , Goldstein Eric , Vedovati Maria Cristina , Paciaroni Maurizio , Liebeskind David S , Yaghi Shadi , Cutting Shawna M
Published: February 2023

Background and Purpose:
Recanalization after cerebral venous thrombosis (CVT) is poorly understood. We aimed to investigate predictors and timing of recanalization in a large, international cohort of patients with CVT.

Materials and Methods:
We used data from the multicenter, international, AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with confirmed CVT from 01/2015 to 12/2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Pre-specified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize. We also examined improvement in recanalization at clinically-relevant time points ( <75 days, 3 months ± 15 days, 6 months ± 30 days, and 12 month ± 30 days) after the initial CVT hospital admission.

Results:
Among the 551 patients (mean age, 44.4 ± 16.2 years, 66% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. In multivariable analysis, older age (OR, 1.05; 95% CI, 1.03 - 1.07), male sex (OR, 0.44; 95% CI, 0.24 - 0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29 - 0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after diagnosis.

Discussion:
Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority of improvement in recanalization and complete recanalization occurred early in the disease course.
Abstract 24: Primary Results Of The Preset For Occlusive Stroke Treatment (prost) Randomized Clinical Trial
Authors: Nogueira Raul G , Hanel Ricardo , Klisch Joachim , Moehlenbruch Markus , Bozorgchami Hormozd , Samaniego Edgar A , Liebeskind David S , Lobsien Donald , Pielenz Daniel , Sauvageau Eric , Aghaebrahim Amin N , Clark Wayne M , Priest Ryan , Ortega-Gutierrez Santiago , Lopes Demetrius , Billingsley Joshua , Haussen Diogo C , Al-Bayati Alhamza R , Siddiqui Adnan H , Chen Michael , Schramm Peter , Narayanan Sandra , Roth Christian , Boeckh-Behrens Tobias , Hassan Ameer E , Fifi Johanna T , Budzik Ronald , Tarpley Jason W , Starke Robert , Raz Eytan
Published: February 2023

Importance:
Clinical trials focusing on new mechanical thrombectomy (MT) technologies have been typically single-arm studies using historical comparison data to determine the safety and efficacy of the novel device. To date, there has not been a contemporaneous prospective, randomized, controlled study comparing standard to newer designed stent-retrievers.

Objective:
To evaluate the safety and efficacy of the pRESET (phenox Ltd) compared to the Solitaire (Medtronic Corp) thrombectomy devices in the treatment of large vessel occlusion strokes (LVOS).

Methods:
Multicenter, prospective, randomized, open-label, blinded endpoint, core lab adjudicated, non-inferiority trial that enrolled 340 patients from October 2019 to February 2022 across 19 US & 5 German sites. Patients aged ≥ 18 years with either anterior or posterior circulation LVOS were included up to 8 hours after symptom onset. Patients were randomly assigned in a 1:1 ratio to either pRESET or Solitaire for the first three device passes.The Primary Endpoint was the proportion of patients achieving a modified Rankin Scale score of 0-2, analyzed by intent to treat with a non-inferiority margin of 0.125 based on the lower bound 95% Confidence Interval. The Primary Safety Endpoint was the proportion of subjects with device- or procedure-related symptomatic intracerebral hemorrhage at 24 (-8/+12) hours as per the SITS-MOST criteria. Secondary Outcome Measures included the rates of (1) Successful Revascularization (defined as expanded Thrombolysis in Cerebrovascular Infarction [eTICI] ≥2b50 ≤3 passes of the assigned device; (2) eTICI ≥2c following the first pass of the assigned device; (3) 90-day mortality and (4) Distribution of 90-day mRS across the entire spectrum of disability (ordinal shift).

Results:
The study database was locked in August 2022. The analysis is ongoing and the final results will be presented at the 2023 International Stroke Conference.

Conclusions and Relevance:
PROST is the first randomized clinical trial aiming to compare a novel versus an established stent-retriever technology, establishing a new scientific benchmark for stroke device trials. (ClinicalTrials.gov: NCT03994822).
Abstract 25: Safety And Outcomes Of Endovascular Thrombectomy In Acute Ischemic Stroke Patients With Recent Use Of Non-vitamin K Antagonist Oral Anticoagulants
Authors: Shah Shreyansh , Simon Dajuanicia N , Mac Grory Brian , Matsouaka Roland , Saver Jeffrey L , Reeves Mathew J , Bhatt Deepak , Smith Eric E , Schwamm Lee H , Fonarow Gregg C , Hernandez Adrian F , Peterson Eric D , Xian Ying
Published: February 2023

Introduction:
An increasing number of patients with acute ischemic stroke (AIS) have recently used non-vitamin K antagonist oral anticoagulants (NOACs). However, there are limited data on safety of endovascular therapy (EVT) in these patients.

Methods:
We performed a retrospective, observational, cohort study of patients treated with EVT within 6 hours of symptom onset in the American Heart Association’s “Get With The Guideline-Stroke Program” between October 2015 and March 2020 to compare safety and functional outcomes in patients who were or were not taking NOACs in the 7 days prior to stroke.

Results:
Of 33,355 patients (median age 72 years (60,81); 50.8% female), 3,727 (11.2%) were taking NOACs, and 29,628 (88.8%) were not taking any oral anticoagulants (OAC) prior to stroke. Compared with those not on OAC, patients taking NOACs were older (median age 75 vs. 71 years) and had a higher prevalence of comorbidities including cardiovascular risk factors, although stroke severity was similar between the groups (median NIHSS 18 vs. 17). After adjusting for baseline clinical factors including intravenous alteplase, patients taking NOACs were not at a significantly higher risk of sICH compared with patients not taking anticoagulants (4.9% vs 6.4%; aOR, 0.93 [95% CI, 0.75-1.14]) or in-hospital mortality (14.1% vs 13.1%; aOR, 0.90 [95% CI, 0.78-1.02]). Of the secondary discharge outcomes, 3 of 7 showed significant differences in favor of the NOAC group including ambulating independently (33.7% vs 38.7%; aOR, 1.15 [95% CI, 1.02-1.30]) and freedom from disability (modified Rankin Scale [mRS] 0-1, 13.0% vs 16.2%; aOR, 1.23 [95% CI, 1.04-1.46]) at discharge. In a subset of patients with documented time of last NOACs dose (n=213), sICH rate was 3.1% (6/196) with last dose ≤2 days and 0% (0/17) with >2 days.

Conclusions:
Among patients with acute ischemic stroke treated with EVT within 6 hours, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of adverse events and was associated with better functional outcomes at discharge.
Abstract 31: The ATTICUS Randomized Controlled Trial - Subgroup Analyses
Authors: Poli Sven , Keller Timea , Martus Peter , Poli Khouloud , Ziemann Ulf , Geisler Tobias ,   on behalf of the Steering Committee and ATTICUS investigators
Published: February 2023

Background:
ATTICUS is the third prospective randomized controlled trial that compared a direct oral anticoagulant (DOAC) vs. acetylsalicylic acid (ASA) for secondary prevention after embolic stroke of undetermined source (ESUS). Aim of ATTICUS was to determine whether apixaban, initiated within 28 days after ESUS, is superior to ASA in preventing new ischemic lesions on 12-month follow- up MRI (primary endpoint) in subjects with remote atrial fibrillation (AF) monitoring.

Methods:
Multicenter (14 German centers) open-label randomized (1:1) controlled trial with blinded endpoint assessment. ESUS patients with at least one risk factor for AF/cardiac thromboembolism (i.e., left atrium (LA) size > 45 mm, spontaneous echo contrast in LA appendage, LA appendage flow velocity ≤ 0.2 m/s, atrial high-rate episodes, CHA2DS2-VASc ≥ 4, patent foramen ovale (PFO)) were enrolled. Study drug was initiated 3 to 28 days after minor/moderate stroke and ≥ 14 to 28 days after major stroke. ClinicalTrials.gov: NCT02427126. Funding by Bristol Meyers Squibb-Pfizer Alliance (Euro 2.2 Mio.) and Medtronic.

Results:
352 patients were available for final analysis. New ischemic lesion(s) were found in 13.6% vs. 16.0% of patients in the apixaban and the ASA arm, respectively (p=0.57), intention-to-treat. AF was detected in 25.6 % of patients. No difference between study arms was found for other thromboembolism, death, SAE, major and clinically relevant bleeds.

Conclusions:
ATTICUS was the first trial testing the concept of DOAC vs. ASA in an enriched ESUS population. Mandatory cardiac monitoring, vessel imaging, and MRI in all ATTICUS patients will help to better understand this complex condition. We will present secondary analyses including on-treatment analysis, prevention of embolic/disabling lesions/strokes, association of stroke pattern with AF occurrence/macroangiopathic changes.
Abstract 46: Cumulative Incidence Of Stroke Disability/mortality Following Emergency Department Discharge For Dizziness
Authors: Kerber Kevin A , Sharp Adam , Baecker Aileen , Burke James F , Sangha Navdeep S , Jancis Molly , Nguyen Huong , Manthena Prasanth , Shen Ernest , Park Stacy , Meurer William J
Published: February 2023

Introduction:
Providers are often concerned about missing stroke in Emergency Department (ED) dizziness visits. Prior studies found that the cumulative incidence of stroke after ED discharge for dizziness is low. However, little is known about the magnitude of disability and/or severity of subsequent strokes which is important for informing the scope of the problem. We aimed to estimate the cumulative incidence of stroke-disability/mortality following ED dizziness visits that were discharged home.

Methods:
We conducted a retrospective cohort study from January 2016 to December 2020 across 13 EDs within Kaiser Permanente Southern California (KPSC). We included all index visits for adults who were discharged home from the ED after a primary dizziness visit, excluding those with DNR/hospice status, trauma, or index stroke diagnosis. Post-stroke disability/mortality - defined as stroke hospitalization not discharged home - was captured over a 30-day follow-up period. Cumulative incidence of stroke-disability/mortality was calculated using Kaplan-Meier estimates censored for non-stroke death. Acute stroke management was also summarized.

Results:
We identified 77,315 index dizziness visits discharged home from the ED. Median age was 59 years (IQR,44-71) and 62% were female. The 30-day cumulative incidence of stroke-hospitalization was 0.12% (95% CI 0.10-0.15%; 1 in 823) and the cumulative incidence of post stroke-disability/mortality was 0.04% (95%CI 0.03-0.06; 1 in 2,342). At the subsequent stroke-hospitalizations, the frequency of acute interventions was as follows: 3% (3/94) intra-arterial thrombolytics, 5% (5/94) thrombectomy, 2% (2/94) suboccipital craniotomy, 3% (3/94) tracheostomy, 3% (3/94) gastrostomy, 10% (9/94) mechanical intubation.

Conclusions:
The cumulative incidence of post stroke-disability/mortality among patients discharged from the ED for dizziness is low and acute interventions used to manage severe strokes were infrequent. These data are important for planning studies to optimize outcomes of patients presenting to the ED for dizziness.