bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 21: At least 1 in 4 Stroke Survivors do Not Achieve Adequate BP Control
Authors: Forman Rachel , Sharma Richa , de Havenon Adam , Williams Jasmin , Xin Xin , Kim Chungsoo , Sheth Kevin , viscoli catherine , Lu Yuan
Published: January 2025

Introduction:
For stroke survivors, blood pressure (BP) reduction significantly lowers the risk of recurrence; a 10mmHg decrease in systolic BP is associated with a 20% risk reduction. Despite the magnitude of this benefit, existing data quantifying post-stroke BP control is limited to small cohorts, national surveys relying on self-report of stroke, and cross-sectional surveys from closed health systems. We aim to determine rates of post-stroke BP control from a broader population within the first year of stroke from multiple cohorts of patients, including from a large US fee-for-service health system, TriNetX (global data source), and two randomized control trials.

Methods:
We analyzed rates of uncontrolled BP (
>
140/90 mmHg) after stroke in 4 cohorts of individuals 18 years or older: 1) patients in the Yale New Haven Health System (YNHHS) between 2015-2020 at 6 months after stroke (both ischemic and hemorrhagic) hospitalization, 2) patients in TriNetX from 01/01/20 to 07/20/2024 with hypertension (ICD-10 code I10) and a hospital diagnosis of ischemic stroke (ICD-10 code I63), 3) participants with ischemic stroke in the Insulin Resistance Intervention after Stroke (IRIS) trial, and 4) the control arm of the blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomized trial. For TriNetX, IRIS, and SPS3, BP was evaluated at one year after hospitalization.

Results:
Among YNHHS patients with stroke [n=3,339; mean age 67, 21% Black race, 10% Hispanic ethnicity, 49% male], the rate of uncontrolled BP was 31%. Ischemic strokes accounted for 83.2% of population, while hemorrhagic strokes accounted for 16.8%. In TriNetX [n= 495,474; mean age 69, 17.7% Black race, 5.9% Hispanic ethnicity, 48.6% male], the rate of uncontrolled BP was 33.4%. In the IRIS trial [n=3,135; mean age was 63, 11% Black race, 4% Hispanic ethnicity, and 67% male], 29% of participants were classified with uncontrolled BP. In the SPS3 trial [n=1,519; mean age was 63, 17% Black race, 31% Hispanic ethnicity, 65% male], 40.1% of participants were classified as uncontrolled BP.

Conclusion:
Among individuals with stroke in clinical trial and real-world cohorts, the rate of uncontrolled BP post-stroke ranged from 29 to 41%. These results support the tremendous need for improved BP management strategies for stroke survivors.
Abstract 26: First-in-human Phase 1/2a Study of Intracerebral Transplantation using Embryonic-derived Neural Stem Cells (NR1) for Chronic Ischemic Stroke (NCT04631406): 12 Months Outcomes
Authors: Steinberg Gary , Bet Anthony , Williams Jennifer , McDonald Kathy , J Diaz Robert , Harryman Samos Cindy , Trisler Kirk , Weissinger Judy , Coburn Maria , Jiang Bin , TONG ELIZABETH , Qin FeiFei , Han Summer , Schwartz Neil
Published: January 2025

Introduction:
Except for vagal nerve stimulation, no treatment exists to restore function in chronic stroke patients. Several prior intracerebral stem cell trials were promising, but are not being further developed.

Objective:
NR1 is a human embryonic derived neural stem cell that improved motor-sensory function in rodent stroke models, and was expanded to produce GMP cryopreserved cell lots. The safety&efficacy of NR1 intracerebral transplantation in chronic stroke patients was assessed over 12 months.

Methods:
Inclusion Criteria: 18-75 yo; 6-60 mos post-ischemic subcortical MCA stroke; mRS 3-4. Subjects were transplanted with 2.5M, 5M, 10M or 20M. Primary Outcomes: Adverse events 0-12 mos; Change in total Fugl-Meyer motor score (FMMS, max 100) compared to baseline at 12 months (≥10 points improvement considered “clinically meaningful”). Other outcomes: UE FMMS, LE FMMS, Gait Speed test, Barthel Index (BI), NIHSS, MR FLAIR, Resting State fMRI and [18F]FDG PET.

Results:
18 patients were transplanted. Adverse events included headache, worsened baseline expressive aphasia and asymptomatic chronic subdural hygroma, all resolving spontaneously. All 17 pts with f/u ≥3 mos demonstrated improved total FMMS and 11 of these 17 subjects showed clinically meaningful recovery in total FMMS. At 12 mos subjects increased 12.1 (+/- 1.8) points for total FMMS (p=0.00002), 7.4 (+/-1.6) points for UE FMMS (p=0.00057), 4.7 (+/-0.5) points for LE FMMS (p =0.0000009), 7.7 (+/-2.5) points for BI, while NIHSS improved by 1.77 (+/-0.47) and gait speed improved substantially. 14/18 pts demonstrated new transient FLAIR signal in premotor cortex at d7, that resolved by 2 mos, which was highly correlated with sustained neurologic recovery. Resting state fMRI showed improved functional brain connectivity in sensorimotor network, both ipsilesionally&contralesionally. FDG PET showed increased activity in the ipsilesional motor cortex&contralesional cerebellum.

Conclusions:
Intraparenchymal transplantation of NR1 cells in chronic stroke patients appears safe and well tolerated. Results suggest improved motor function starting at 1 mos and increasing to clinically meaningful recovery in most patients at 12 mos post-implant. UE FMMS improvement surpassed vagal nerve stimulation outcomes.
Abstract 29: Non-gated Dual-source Photon-counting CT Angiography Can Detect Cardioembolic Sources Of Acute Ischemic Stroke At The Primary Investigation: A Retrospective Consecutive Cohort Study
Authors: Stahl Fredrik , Szum Adrian , Damlin Anna , Planken R. Nils , Coutinho Jonathan , Granberg Tobias , Lundberg Johan
Published: January 2025

Introduction:
Early identification of the etiology of ischemic stroke is crucial for secondary prevention. Recent publications on dedicated ECG-gated cardiac CT showcase the potential to detect sources of cardiac embolism.

Photon-counting CT (PCCT) uses semiconductors to convert X-ray photons into electrical signals directly. This allows for improved image quality and lower radiation dose compared to conventional CT. Exploiting PCCT technology with a high-pitch dual-source image acquisition may render an exceptionally high temporal resolution.

We hypothesized that non-ECG-gated high-pitch dual-source PCCT angiography from the diaphragm to the brain might provide added clinical value in detecting cardiac stroke sources during initial stroke imaging while maintaining optimal brain and neck image quality.

Methods:
Consecutive patients with a clinical suspicion of acute stroke imaged with a PCCT system between October 4
th
, 2023 and April 13
th
, 2024 at a Swedish comprehensive stroke center were included. Diaphragm to brain coverage was obtained in an acquisition time of 1.3 seconds; on average, yielding a dose-length product of 360 mGy*cm for the study participants (2.34 mSv). Image quality was graded using a 4-point Likert scale. Images were assessed for cardiac stroke sources. Where available, reference standard echocardiography results were collected.

Results:
Of 249 consecutive stroke investigations, 193 included cardiothoracic imaging, which constituted the study population. 126 scans (65.3%) were cases with imaging confirmed ischemic stroke. The median age was 74 (IQR, 61-81) years, 99 were male (51.3%). In total, 39.4% underwent follow-up echocardiography.

Image quality of the heart was excellent in 19 scans (9.8%) good in 97 (50.3%), moderate in 72 (37.3%), and poor in 5 scans (2.6%). Fourteen (7.3%) certain or probable interatrial septal defects were found in the study population. In the imaging-confirmed ischemic stroke subgroup, six certain or probable cardiac thrombi were found (4.8%). Additionally, a possible cardiac thrombus was found in 31 instances (24.6%). Three aortic valve vegetations were found (2.4%), all confirmed by echocardiography.

Conclusions:
Non-ECG-gated high-pitch dual-source PCCT angiography typically provides images of high quality, at virtually no time expense while maintaining a reasonably low radiation exposure. Non-gated PCCT angiography is a promising technique to be used as a primary screening method for cardioembolic stroke.
Abstract 45: Time to Treatment in Intracerebral Hemorrhage Across the United States
Authors: Melmed Kara , Lele ABHIJIT , Ayodele Mara , Goldstein Joshua , LacKamp Aaron , Dombrowski Keith , Alkhachroum Ayham , Mainali Shraddha , de Havenon Adam , Krishnamohan Prashanth , Subramaniam Thanujaa , Stretz Christoph , Lee Wen-Yu , Kuohn Lindsey , Fong Christine , Houghton Margaret , Campbell Alexis , Song Shlee , O'Phelan Kristine , Sheth Kevin , Venkatasubramanian Chitra , Yaghi Shadi , Mayer Stephan , Diaz Ivan , Frontera Jennifer
Published: January 2025

Introduction:
Contrary to improved mortality in acute ischemic stroke (AIS), mortality of intracerebral hemorrhage (ICH) remains high. This may be attributable to delays in acute treatments for ICH patients. We aimed to establish the current time to treatment in ICH patients across the U.S., compare this to AIS patients, and assess the impact of treatment times on outcomes.

Methods:
This multicenter cross-sectional retrospective study pooled ICH and AIS patients aged ≥ 18 years with admission between January 1, 2017 to December 31, 2022 to acute care hospitals nationwide participating in the Get with the Guidelines-Stroke quality improvement registry. Baseline demographics, clinical variables including time to treatment (antihypertensive agent, hemostatic agent, neurosurgery, thrombolytic or thrombectomy) were abstracted and compared using classical statistics. Logistic regression and time dependent Cox analysis were performed to assess the impact of time to treatment on discharge disposition and mortality in ICH patients.

Results:
We identified 3,344 ICH patients (mean (standard deviation) age 66(16) years, 43% female, and 5,386 AIS patients (mean (SD) 69(15) years, 48 % female) across eleven hospital systems. Median door to CT time was significantly longer in ICH compared with AIS patients at 26[12-69] vs14[8-25] minutes.

Median NIHSS for ICH patients was significantly higher (13[5-25]) than AIS patients (10[4-18]). In ICH patients, median[IQR] arrival systolic blood pressure (SBP) was 179[160-205] mm HG and anticoagulation (AC) use was documented in 13.8%. Door to first treatment was 67[32-246] minutes for ICH patients and 55[35-114] minutes for AIS patients. ICH patients had a greater length of stay (7[3-14] days vs 5[2-9] days) and a higher median discharge mRS (4[3-6] vs 3[1-4]), p < 0.01 for all). Controlling for age, gender, race/ethnicity, NIHSS score, door to ED evaluation, prior AC use, arrival SBP and admission INR, the 1,047(31%) patients who were treated within 60 minutes from arrival had a higher likelihood of discharge to home or acute rehab; OR 1.73 95% CI (1.01-2.97). Time to antihypertensive treatment was a significant predictor of time to death with a hazard ratio (HR) of 1.22(1.03-1.45, p= 0.02).

Conclusion:
Compared to AIS patients, time to treatment for ICH patients is generally longer. Faster treatment times were associated with better discharge outcomes. These findings emphasize the need for improved time metrics in ICH care.
Abstract 54: Stroke Incidence by Race in a Large, Biracial Population Over Time: 2020 Update
Authors: Stanton Robert , Robinson David , Ding Lili , Menzies Lauren , Wechsler Paul , LaPorta Joseph , Aziz Yasmin , Slavin Sabreena , Wright Shea , Nobel Lisa , Walsh Kyle , DeLosRiosLaRosa Felipe , Ferioli Simona , Stamm Brian , Haverbusch Mary , Mackey Jason , Mistry Eva , Demel Stacie , Coleman Elisheva , Jasne Adam , Star Michael , Martini Sharyl , Adeoye Opeolu , Flaherty Matthew , Khatri Pooja , Woo Daniel , Broderick Joseph , Kissela Brett , Kleindorfer Dawn
Published: January 2025

Background:
Understanding the trends of stroke incidence and how those strokes are distributed across race is a critical step to implement trials and programs to decrease the burden caused by stroke nationally. In 2015, we reported that stroke incidence is decreasing in both Black and White adults. We investigated the continued trends in stroke incidence by race in 2020.

Methods:
In this population-based stroke surveillance study, all cases of stroke within a 5-county population surrounding Cincinnati in adults aged ≥20 years were ascertained during a full year every 5 years from 1993 to 2020. Cases were abstracted by study nurses and adjudicated by trained study physicians. Temporal trends were evaluated by age, race (Black or White), and subtype (ischemic stroke (IS), intracranial hemorrhage (ICH), or subarachnoid hemorrhage (SAH)). Stroke incidence rates per 100,000 individuals from 1993 to 2020 were calculated using US Census data and age-, race-, and sex-standardized as appropriate. Trends were evaluated using linear regression. Disparities were evaluated using risk ratios and reported with 95% CIs.

Results:
In 2020, we identified 2280 first-ever strokes. Of these, 23% (N=524) were Black adults and 52% (N=1,177) were female. The overall annual incidence of stroke in 2020 was 203/100,000. Table 1 reports the temporal trends of stroke incidence by subtype for both Black and White race from 1993 to 2020. For all races, any stroke
increased
between 2015 and 2020 (p=0.003, driven largely by an increase in stroke in White adults), while the overall trend since 1993 is no longer declining. Ischemic stroke also increased between 2015 and 2020 (pairwise comparison, p=0.011) in all races. Figure 1 shows the stroke incidence rate of overall stroke (any subtype) over time. The overall risk ratio of any incident stroke between Black and White adults was RR 1.84 (1.66, 2.02; p-value 0.022).

Conclusions:
Compared to our analysis after our 2015 study, overall stroke incidence over time is no longer decreasing. Between 2015 and 2020, we observed an increasing rate of stroke in our population. For the first time in a 27-year period we report a significant increase in stroke incidence, mostly driven by an increase in ischemic stroke incidence in whites. ICH/SAH rates are stably higher in blacks compared to whites. More work needs to be done to investigate any possible association to COVID or other traditional risk factors to address racial disparities in stroke burden.
Abstract 62: Symptoms Experienced at End-of-Life in Patients with Severe Acute Brain Injury
Authors: Das Gitanjali , Crawford-Crudell Willow , Brumback Lyndia , Zahuranec Darin , Creutzfeldt Claire
Published: January 2025

Background:
Palliative care has made important strides in the management of end-of-life symptoms for patients with cancer, though we have little understanding of end-of-life symptoms in patients with stroke and severe acute brain injury. As acute stroke management advances and more patients survive the acute phase of SABI, we aim to improve our understanding of their symptoms at end-of-life.

Objectives:
To describe symptoms in the last week of life of patients with SABI, as reported by family members, using a validated symptom inventory scale.

Methods:
This study is part of an ongoing prospective observational study of hospitalized patients with SABI and their family members at two academic institutions. Eligible patients were adults (>=18) admitted with ischemic stroke, intracerebral hemorrhage, or coma after cardiac arrest as the primary reason for hospitalization and who met at least one severity criteria (e.g. ≥NIHSS 10 on day 2). Family members completed a post-death survey that included the validated 22-item integrated Palliative outcome scale (iPOS). A symptom was defined to be prevalent if reported as “severely” or “overwhelmingly”. Given the novel use of iPOS in stroke, we also explored factors associated with missingness of iPOS items.

Results:
We enrolled 303 patients and 352 family members. Of these, 165 patients were known to have died, with 149 having at least one family member complete a post-death survey. Descriptive characteristics are shown in Table 1. Median days from admission to death were 10, from death to survey completion 56. Of the 149 families, 138 (93%) responded to the iPOS question about patient pain while only 64% responded about hallucinations. Among responders, ≥60% reported poor patient mobility and difficulty communicating, and >50% reported patient fatigue and difficulty remembering things (Figure 1). All 22 iPOS items were completed for only 79 (<50%) participants. Family members who are older or have lower health literacy are more likely to miss at least one item (Table 2).

Discussion:
According to family members, over 20% of patients with SABI at end-of-life suffer from severe pain and shortness of breath, while over 50% have severe fatigue and poor mobility. While family response rate to some symptom items, e.g. patient pain, is high, less than half completed all 22 iPOS items. More work is needed to further understand symptoms and develop interventions to ensure high quality end-of-life care after SABI.
Abstract 63: Medicare Advantage Appears to Promote Stroke Prevention and Functional Independence Measure Gains with Lower Utilization than Fee-for-Service Medicare
Authors: Bian Emily , Menon Priyanka , Worrall Bradford , Crowe Jonathan
Published: January 2025

Introduction:
Stroke prevalence is highest in adults ages
>
65 years, the majority of whom are Medicare beneficiaries. Fee-for-Service (FFS) Medicare incentivizes utilization by paying for each service. Medicare Advantage (MA) uses capitated payments to reduce overutilization. It is unknown if MA beneficiaries with stroke receive more stroke prevention care as a strategy to lower utilization. We examine this question by reviewing studies comparing clinical measures, utilization, and outcomes in FFS and MA.

Methods:
We performed an empirical integrative narrative review of the Pubmed, Embase, and OVID databases according to PRISMA guidelines to compare stroke care between MA and FFS. Cholesterol control, blood sugar management, tobacco cessation, and blood pressure management were chosen using the American Heart Association’s Life’s Crucial 9 for their Medicare coding availability. Anticoagulation for atrial fibrillation (AF), acute and post-acute care utilization, and outcomes were added. We included studies if
>
20% of the patient population had strokes and excluded studies prior to the Medicare Modernization Act (2003) to accurately assess MA.

Results:
9/544 studies met inclusion criteria (Figure 2). One found higher LDL levels (81.5 mg/dL vs 78.9 mg/dL) and statin prescription rates (Standardized Difference 32%) in MA than FFS (2). MA beneficiaries had slightly higher HgbA1C in one study. Two showed mixed rates of antihyperglycemic medications in MA. Tobacco cessation counseling was more likely in MA (aOR 1.05, 95% CI 1.02-1.09) (2). MA beneficiaries had slightly higher systolic blood pressure but no difference in blood pressure control. Oral anticoagulation use for AF was higher in MA than FFS (75.52% vs 69.96%), as was adherence (41.14% vs 33.70%) (7). Index hospitalization and post-acute care utilization, including hospital readmission, appeared lower in MA. We calculated higher Functional Independence Measure gains in MA (Figure 3). One study showed non-significant lower mortality in MA (4). Another showed lower mean mortality and 0.5% higher 90-day mortality in MA (9).

Conclusion:
Published studies suggested that MA emphasizes preventative care for stroke patients, particularly for hyperlipidemia, smoking, and AF, without showing favorable selection in MA. Acute and post-acute care utilization was lower in MA. Improvements in functional outcomes were greater. Mortality data was mixed. Future cohort studies are needed to better understand these dynamics.
Abstract 69: Both Infarct and Non-infarcted Brain Regions Drive Acute Deep Learning Based MRI Prediction of Stroke Outcome
Authors: Liu Yongkai , Voorst Henk , Jiang Bin , Yu Yannan , Zaharchuk Greg
Published: January 2025

Purpose:
Predicting long-term outcomes from early acute ischemic stroke (AIS) information is crucial for prognostication, resource management, and clinical trials. Current methods predominantly depend on infarct-related features, such as size and location, for outcome predictions, and demonstrate limited correlation with outcomes. This study examines how deep learning leverages different brain regions, including non-infarct areas, to improve the accuracy of 90-day outcome predictions in AIS patients.

Materials and Methods:
We developed and validated deep learning (DL) models on a cohort of 436 AIS patients, using MRI diffusion-weighted imaging scans from 1-7 days post-stroke and 90-day modified Rankin Scale (mRS) follow-up data. These models were trained on various inputs— infarct volumes, whole-brain images, infarct masks, intensity-preserved infarct masks, and images in which the infarct region is removed, which we call infarct-neutralized images, and which enable an assessment of overall brain health. Model performance was assessed based on the accuracy of predicting the specific mRS score, accuracy within ±1 mRS category, mean absolute error (MAE), and the ability to predict unfavorable outcomes (mRS > 2) using receiver operator curve (ROC) metrics.

Results:
The infarct volume model had the highest (worst) MAE of 1.48 points (95% CI: 1.38-1.58, p < 0.001), while the whole-brain model achieved the lowest (best) MAE of 1.08 points (95% CI: 1.00-1.17). Models with intermediate imaging information—such as infarct masks (MAE 1.28, 95% CI: 1.19-1.37, p = .002), intensity-preserved infarct masks (MAE 1.27, 95% CI: 1.18-1.37, p = .009), and infarct-neutralized images (MAE 1.33, 95% CI: 1.24-1.43, p < .001)—improved upon the volume-only predictions. For predicting unfavorable outcomes, the infarct volume model had the lowest performance (AUC 0.70, 95% CI: 0.65-0.75; p < .001), while the whole-brain model achieved the highest AUC of 0.85 (95% CI: 0.82-0.89), outperforming the infarct mask (AUC 0.80, 95% CI: 0.76-0.84; p = .01), intensity-preserved infarct mask (AUC 0.80, 95% CI: 0.76-0.84; p = .007), and infarct-neutralized images (AUC 0.74, 95% CI: 0.69-0.79; p < .001)

Conclusions:
The best predictive performance was achieved using voxel values from the entire brain, showing that both infarcted and non-infarcted regions contribute significantly to accuracy. Non-infarcted areas may reflect overall brain health and resilience, informing potential outcomes.
Abstract 76: Characterization of the Cerebral Aneurysm Microenvironment Using Spatial Multiomics
Authors: Barak Tanyeri , Gultekin Batur , Kilic Deniz , Avsar Timucin , Miyagishima Danielle , Kivrak Can , Peksen Ayse Buket , Gutierrez Ana , Karadag Cihat , Yalcin Kanat , Ercan-Sencicek Adife Gulhan , McGuone Declan , Bayri Yasar , Kilic Turker , Gunel Murat
Published: January 2025

Introduction:
Intracranial aneurysms (IAs) are abnormal dilations of brain arteries that can result in high mortality and morbidity when they rupture. Our study provides a spatial characterization of 11 human IA tissues by utilizing spatial transcriptomics and proteomics with 6,000 RNA and 64 protein markers, serving as a comprehensive atlas of the IA microenvironment.

Methodology:
Nanostring CosMX platform was used to spatially characterize proteomic and transcriptomic profile of the IA- and the parental vessel wall in 11 fresh-frozen or fixed post-mortem IA-tissues at single cell resolution. We used a data diffusion-based filtration method, sPARC, to recover gene/protein dynamics. Squidpy and scanpy packages were used for data visualization.

Results:
Ripley-L function demonstrated significant spatial patterning and enrichment of myofibroblasts in the IA-wall and the
RHOB
-high vascular smooth muscle cells (VSMC) in normal vessels. Moran`s-I was used for spatial autocorrelation, which revealed genes with the most significant spatial patterning, including
RHOB
,
DES
in normal vessel wall and
IGFBP7
,
VCAN
in the IA-wall, which showed the highest expression where the media thickness was decreased. We found that the components of the complement system including,
C1QA
and
C1QB
were enriched at ruptured area. We demonstrated that adventitia-fibroblasts on the IA-wall undergo a phenotypic transition from
NDUFA3
-high fibroblasts to immune-interacting
DCN
/
SERPINE2
-high fibroblasts. At protein level, HLA-DR, a marker for antigen presenting cells was found almost exclusively in the adventitia of IA-wall, further supporting the immune-regulatory role of adventitia in the IA-pathogenesis. Furthermore, cell type specific analysis of VSMC revealed significant upregulation of NFkB-p65 and its upstream regulator and a DNA-sensing molecule, STING. Integration of RNA and the protein data revealed a strong overlap of
IGFBP7
-high regions with STING/NFkB p65-high areas, suggesting a potential role of a novel a IGFBP7–STING–NFkB axis in IA-pathogenesis.

Conclusion:
Our study provides a comprehensive characterization of the IA microenvironment using a spatial multiomic approach, identifying gene/protein expression profiles, cell states, inter-compartmental crosstalk associated with IA formation and rupture.
Abstract 77: Three Dimensional Aneurysm Wall Enhancement Improves the Prediction of Symptomatic Presentation: A Multicenter Study
Authors: Zhu Chengcheng , Sagues Elena , Tian Bing , Zhao Huilin , Gudino Andres , Dier Carlos , Salinas Ivonne , Cabarique Martin , Noboa Luis , Ojeda Diego , Samaniego Edgar
Published: January 2025

Background:
Managing unruptured intracranial aneurysms (IAs) involves balancing procedural risks with the long-term risk of rupture. Aneurysm wall enhancement (AWE) has been associated with aneurysm instability and symptomatic presentation. However, assessing AWE typically relies on subjective two-dimensional visual inspection, which lack objectivity. This study aims to evaluate a predictive model for symptomatic status by integrating clinical, morphological, and three dimensional-AWE (3D-AWE) metrics from a large dataset of IAs.

Methods:
Patients from three large academic center from the US and China, with saccular unruptured IAs underwent 3T high-resolution magnetic resonance imaging. Morphological assessment was conducted through angiographic studies. The determination of AWE was performed using a 3D-mapping pipeline that quantifies the average signal intensity of the aneurysm wall after contrast administration producing an objective metric: 3D-AWE (figure). Symptomatic status was defined by rupture, sentinel headaches, cranial nerve palsy, and focal neurological symptoms due to mass effect by the aneurysm. The optimal multivariate model for predicting symptomatic presentation of IAs was determined using an all-subsets regression approach.

Results:
A total of 389 IAs were included, with 73 (19%) being symptomatic at presentation. The model using clinical and morphological aneurysm variables achieved an AUC of 0.78, with 60% sensitivity and 86% specificity in identifying symptomatic aneurysms. Adding 3D-AWE metrics improved the model's performance, increasing the AUC to 0.82, with 73% sensitivity and 78% specificity. High-risk locations (anterior communicating, posterior communicating, and basilar arteries; OR 1.87, p 0.04), size ratio (OR 1.52, p<0.001), smoking (OR 1.91, p 0.07), and positive 3D-AWE (OR 7.09, p<0.001) were identified as independent predictors of symptomatic presentation.

Conclusions:
Incorporating objective 3D-AWE data enhanced the predictive performance of clinical and morphological information for detecting symptomatic IAs.
Abstract 80: Predictors of Procedural Outcome after Surface-Modified Flow Diverter Treatment for Intracranial Aneurysms: An Update from the INSPIRE-A Registry
Authors: Meyer Lukas , Kniep Helge , Szikora Istva , Martínez-Galdámez Mario , Lamin Saleh , Holtmanspoetter Markus , Turjman Francis , SPELLE Laurent , Fiehler Jens
Published: January 2025

Introduction:
Although flow diverters (FD) are a long-established treatment-option for brain aneurysms, the evidence of data associated with therapy success is still based on relatively small heterogeneous studies. Recent data from a large prospective registry with highly standardized, independent adjudication might provide more insights.

Methods:
The INSPIRE-A registry is a prospective, single arm study of brain aneurysms treated with commercially available Medtronic devices, including latest FD technology with surface modifications. The registry collects data from 70 centers in 21 countries. Results are adjudicated by an independent Imaging Core Laboratory and a Clinical Events Committee. The association of patient characteristics, aneurysm details, and procedural variables with aneurysm occlusion (Raymond–Roy occlusion classifications [RROC I]), and in-stent stenosis at 1 year follow-up (FU) were tested using multivariable logistic regression analysis.

Results:
786 patients were analyzed. The median age was 55 years (IQR, 46-64) and 79.6% (626) were female. Most frequently, aneurysms were in the anterior circulation (89.8 %, 706) with highest rates of ICA-Aneurysms (75.3%, 592) in the C6 (52.7%, 312/592). Median diameter and neck width of aneurysms were 7.2 mm (IQR, 5-11) and 6.5 mm (IQR, 4-10), respectively. 91.7% (719) of aneurysms were saccular. The Pipeline Flex with Shield technology (Medtronic, Irvine CA) device was deployed in 58% (456), the Pipeline Vantage with Shield technology (Medtronic, Irvine CA) device in 42% (330). Adjunctive coiling was used in 19.8% (156). At 1 year FU, RROC I was observed in 74.3% (584) of cases. In multivariable analysis, increasing age (OR, 0.97, 95% CI, 0.96-0.99; p<0.001), male sex (OR, 0.51, 95% CI, 0.34-0.77; p=0.001), and adjunctive coiling (OR, 1.62, 95% CI, 1.0-2.56; p=0.037) were significantly associated with RROC I. There was a tendency of higher occlusion rates in ICA-Aneurysms (OR, 2.91, 95% CI, 1.42-2.56; p=0.076). In-stent stenosis occurred in 2.2% (17) and was associated with fusiform morphology at 1 year FU (OR, 4.82, 95% CI, 1.28 -14.35; p=0.018).

Conclusion:
Treatment with surface-modified FD for intracranial aneurysms led to favorable rates of complete aneurysm occlusion at 1 year FU. This large, homogenous, and independently adjudicated data set suggests that age, gender, and adjunctive coiling were associated with complete aneurysm occlusion. Fusiform morphology was associated with in-stent stenosis.
Abstract DP16: Plasma Proteomics and Machine Learning Algorithms Nominate Proteins Indicative of Stroke Severity in Acute Ischemic Stroke
Authors: Misra Shubham , Natu Aditya , Kumar Prateek , Frankel Michael , RANGARAJU Srikant
Published: January 2025

Introduction:
The National Institutes of Health Stroke Scale (NIHSS) provides a clinical measure of stroke severity. Molecular biomarkers that reflect severity of neurological injury may enhance the objectivity and accuracy of stroke severity assessment.

Objectives:
This study aimed to discover plasma proteins indicative of stroke severity in patients with acute ischemic stroke (AIS) using aptamer-based proteomics and supervised machine learning algorithms.

Methods:
We used clinical and proteomics data of AIS patients aged ≥18 years lodged within a prospective plasma repository from 2010 to 2014. We collected blood from each patient at hospital admission before administering any therapeutic intervention. Our outcome was differentially expressed levels of proteins in AIS patients classified by NIHSS scores. We classified AIS patients into mild NIHSS (0-7), moderate NIHSS (8-10), severe NIHSS (11-20), and critical NIHSS (21-42) subgroups. We performed aptamer-based proteomics using the plasma 7K SomaScan assay. For comparisons between the four NIHSS subgroups, we performed feature selection by sparse partial least squares discriminant analysis (sPLS-DA) using the MixOmics R package. We determined the area under the receiver operating characteristic curves (AUC-ROC) to classify the AIS-severity subgroups.

Results:
We included 40 AIS patients (mean age 63.3 years, 45% males) classified into four subgroups: 10 mild NIHSS, 9 moderate NIHSS, 11 severe NIHSS, and 10 critical NIHSS (Figure 1). SomaScan quantified 7307 protein targets, including 6373 unique proteins. Using the sPLS-DA approach, we identified two components classifying critical NIHSS (component 1, 10 proteins) and mild and severe NIHSS (component 2, 35 proteins) from moderate NIHSS. The panel of 45 proteins from the two components had an AUC of 0.96 to classify mild NIHSS, 0.66 to classify moderate NIHSS, 0.96 to classify severe NIHSS, and AUC of 0.97 to classify critical NIHSS from other subgroups. The top 5 proteins for AIS risk stratification were SELENOW, ANGPTL4, FABP3, CFL2, and KDM8 (Figure 2).

Conclusions:
Our study revealed distinct panels of protein biomarkers capable of classifying AIS patients into NIHSS-defined severity subgroups with high accuracy, particularly for mild, severe, and critical categories. These proteins may improve stroke severity assessment, especially in conditions where a clinical exam is limited, though further validation with larger cohorts is critically needed.
Abstract DP17: Higher Pre-Admission Blood Pressure Is Associated with Lower Initial Infarct Volume after Acute Large Vessel Occlusions
Authors: Galecio-Castillo Milagros , Shogren Sophie , Begunova Yelyzaveta , Olexa Madelynne , Kalakoti Piyush , Cruz-Criollo Leonardo , Petersen Nils , Ortega-Gutierrez Santiago
Published: January 2025

Introduction:
Following a large vessel occlusion acute ischemic stroke (LVO-AIS), cerebral autoregulation is notably compromised, making cerebral blood flow maintenance and optimal blood pressure (BP) crucial to preserving the penumbral tissue until reperfusion. While intraprocedural BP drops and high post mechanical thrombectomy (MT) BP are associated with unfavorable outcomes, data on pre-admission BP's impact on infarct growth is markedly scarce.

Methods:
This retrospective cohort study from two centers included anterior circulation LVO-AIS patients treated with MT from Jan-2018 to Dec-2021. Admission CTP parameters were: Initial infarct volume (rCBF<30%), hypoperfused tissue (Tmax>4s,6s,8s,10s). Hypoperfusion intensity ratio (HIR, Tmax 10s/6s) served as a collateral status surrogate. Infarct growth rate (IGR) was defined as rCBF<30%/stroke onset-to-CTP time. BP, measured with non-invasive cuffs, was obtained from Emergency Medical Services reports. For each patient, mean SBP (mSBP), mean MAP (mMAP) and BP drops (difference between highest and lowest MAP) were calculated. We used multivariable regression to evaluate associations between hemodynamic and neuroimaging parameters.

Results:
171 patients were included in the study. Median age was 71 yrs [IQR 64–81], and 48.5% were women. 117 patients (92.9%) had baseline mRS 0-2, median NIHSS and ASPECTS were 15 [10–20] and 8 [7-9]. Median mSBP was 145 mmHg [134–162], median mMAP 104 [94–112] and median dMAP 17 mmHg [12-30]. For each unit increase in mMAP, the rCBF<30% decreased by 10% (adjusted coefficient 0.90,

p
<0.001

), and the IGR decreased in 9% (aCoeff. 0.91,

p
<0.001

) after adjusting for symptoms onset to CTP time, age, admission NIHSS and IVT. For each unit increase in mean SBP, Tmax >6s increased by 3% (aCoeff. 1.03,

p
=0.021

), and IGR decreased in 3% (aCoeff. 0.97,

p
=0.038

) (
Figure 1).
Importantly, the association between mMAP and lower rCBF<30% was higher in patients with good collateral status stratified by HIR 0.4
(Figure 2)
.

Conclusion:
Higher pre-admission mMAP is linked to reduced initial infarct volume, and both mMAP and mSBP are associated with slower early IGR. These findings were consistent in patients with favorable collateral status, as opposed to patients with poor collaterals. These insights underscore the complex role of BP management in LVO-AIS and the need for further prospective studies on BP interventions targeting high BP preservation, while considering individual hemodynamics.
Abstract DP20: An Evaluation of Stroke Literature Pamphlets For Stroke Patients
Authors: Degen Nathaniel , Sivakumar Milan , Varkey Thomas , Alexandrov Andrei , Singh Savdeep
Published: January 2025

Background:
The American Stroke Association developed a series of pamphlets aimed at educating patients and families about strokes (https://www.stroke.org/en/professionals/stroke-resource-library), and these materials are often used by healthcare professionals to help communicate critical information about strokes. The effectiveness of these pamphlets depends on the readability of the content. Given that the average American is able to comfortably read at an eighth-grade level or below, it is essential to assess whether these materials are appropriately tailored to meet the needs of the general public.

Methods:
This study evaluated 50 stroke-related pamphlets available in the PDF format from the American Stroke Association website, which fell into one of three categories: prevention, acute treatment, and post-stroke care. The text from each pamphlet was analyzed using the Gunning Fog index and Flesch-Kincaid Ease and Grade level programs. All of the values for each of the PDF were recorded in an excel sheet for further data analysis.

Results:
The average Gunning Fog Index was 13.1 ± 4.0 (SD) (equivalent to at least some college level education) and the average Flesch-Kincaid Grade Level was 10.1 ± 3.8 (SD) (equivalent to around a 10th grade education). To meet the readability standards appropriate for an 8th grade education level or below, target scores should be below 8.5 for Gunning Fog Index and 8.5 for Flesch-Kincaid Grade Level.

Conclusion:
The patient education materials analyzed in this study were equivalent to 10th and 13th grade reading level. These findings highlight the need for improving the readability of patient education resources by adjusting language and explanations to lower education levels.

Keywords: stroke, readability, health literacy, patient education
Abstract DP30: Inhibition of nitric oxide synthase transforms carotid occlusion-mediated benign oligemia into
de novo
large cerebral infarction
Authors: Kim Ha , Chung Jinyong , Schellingerhout Dawid , Lo Eng , Faber James , Ayata Cenk , Kim Dong-Eog
Published: January 2025

Background&Objectives:
It remains unclear why unilateral proximal carotid artery occlusion (UCAO) causes benign oligemia, without progressing to cerebral infarction, in mice, yet leads to a wide variety of outcomes (asymptomatic-to-death) in humans. We hypothesized that inhibition of nitric oxide synthase (NOS) both transforms UCAO-mediated oligemia into full infarction and expands preexisting infarction.

Methods:
Using 900 mice, we i) investigated stroke-related effects of a single intraperitoneal dose of the NOS inhibitor N
ω
-nitro-L-arginine methyl ester (L-NAME, 400 mg/kg) + UCAO; ii) examined the rescue effect of the NO donor, molsidomine (200 mg/kg, at 30 minutes); iii) tested the impact of antiplatelet medications; iv) queried if UCAO without L-NAME administration could induce infarction when mice had hyperglycemia and hyperlipidemia; and v) measured blood levels of endogenous NOS inhibitors (asymmetric and symmetric dimethylarginines; ADMA and SDMA, respectively). Furthermore, we conducted i) a multi-center study (n=438 UCAO patients) to identify predictors of infarct volume and ii) Mendelian randomization analysis to estimate the causal effect of the endogenous NOS inhibitors on human ischemic stroke.

Results:
UCAO alone induced infarction rarely (~2%) or occasionally (~14%) in C57BL/6 and BALB/c mice, respectively. However, L-NAME+UCAO induced large-arterial infarction in ~75% of C57BL/6 and BALB/c mice. Laser speckle imaging for 6 hours detected spreading ischemia in ~40% of C57BL/6 and BALB/c mice with infarction (vs. none without), as assessed at 24 hours. In agreement with vasoconstriction and microthrombus formation shown by intravital microscopy, molsidomine and the endothelial NOS-activating antiplatelet cilostazol attenuated or prevented progression to infarction. Moreover, UCAO without L-NAME caused infarction in ~22% C57BL/6 and ~31% ApoE knock-out mice with hyperglycemia and hyperlipidemia, which, in turn, associated with ~60% greater SDMA levels. Further, increased levels of glucose and cholesterol associated with significantly larger infarct volumes in UCAO patients. Lastly, Mendelian randomization identified a causative role of NOS inhibition, particularly in elevated SDMA concentration, in ischemic stroke risk (OR=1.24; 95% CI, 1.11–1.38;
P
=7.69×10
-5
).

Conclusions:
NOS activity is a key factor determining the fate of hypoperfused brain following acute carotid occlusion or clamping, where SDMA could be a potential risk predictor.
Abstract DP33: Under-representation of No Mismatch Patients in Large Core Trials
Authors: McCullough-Hicks Margy , Seners Pierre , Mlynash Michael , Olivot Jean Marc , Heldner Mirjam , Mordasini Pasquale , Strambo Davide , Michel Patrik , Carrera Emmanuel , Heit Jeremy , Lansberg Maarten , Albers Gregory
Published: January 2025

Background:
Absence of a perfusion Mismatch (MM) profile suggests that the volume of salvageable penumbral tissue is small or absent. There is uncertainty regarding the benefit of endovascular therapy (EVT) in large ischemic core patients without MM. Although these patients were eligible for recent prospective randomized trials, few ultimately were enrolled. We sought to compare the expected percentage of MM versus No MM encountered in clinical practice compared to enrollment in large core clinical trials stratified by time since last known well.

Methods:
We used a retrospective multicenter international study of patients with anterior circulation large vessel occlusion strokes, baseline MR or CT perfusion (MRP, CTP), and definitive last known well (LKW) within 24 hours. We compared this to the SELECT2 and ANGEL-ASPECT randomized clinical trials of EVT in large core ischemic stroke. A MM profile was defined as mismatch ratio ≥1.2 and penumbral volume ≥10ml. Large core was defined as ≥50ml on CTP (volume of relative cerebral blood flow <30%) or MRP (volume of apparent diffusion coefficient value of <620 x 10-
6
mm
2
/s), in keeping with the SELECT2 trial enrollment criteria. We used the Cochran-Armitage Trend Test to evaluate for trends in MM presence over time. There was potential bias in favor of a higher proportion of MM in our dataset because one hospital’s transfer patient acceptances were based on favorable CTP profiles at spoke hospitals.

Results:
Of 2,012 patients, 444 had core ≥50ml. Among these patients, 161 (36%) had a No MM profile, median core infarct size was 112ml (IQR 68-137). 53% were male, median age was 72 (59-81), median baseline NIH Stroke Scale was 19.5 (16-24), median time from LKW was 4.3 hours (2-8.7), and 35.8% had CTP as baseline perfusion modality. Figure 1 shows a trend toward decreasing MM over time since LKW (P=0.01). By comparison, 29 of 352 (8%) patients enrolled in the SELECT2 trial had a No MM profile, 8 of whom were randomized to EVT (Figure 2). 31 of 426 (7%) patients enrolled in ANGEL-ASPECTS had a No MM profile; 15 underwent EVT, only 2 in the 12-24 hour since LKW well epoch (Figure 3).

Conclusions:
The proportion of patients with No MM enrolled in large core trials was substantially smaller than encountered in routine clinical practice, particularly in the late time windows. Additional data on the response to EVT in these patients, who have evidence of a potentially completed or nearly completed infarct, is needed.
Abstract DP42: A Stroke Case Management Program To Improve Hospital Readmission Rates After Index Stroke
Authors: Kim Kyutae , Jaberizadeh Amir , Tucker Lue-Yen , Malekyan Cristin , Mena Sarah , Shirazi Aida , Lynch Meaghan
Published: January 2025

Introduction:
The transitional period from hospital discharge to the community for stroke survivors is a vulnerable time as patients navigate healthcare systems with their new impairments. Stroke related readmission rates are highest within the first year of the index stroke. This institution created the Stroke Transitions Program to improve patients’ healthcare after hospital discharge for a stroke.

Hypothesis:
Stroke survivors enrolled in the Stroke Transitions Program reduces their 1 year hospital readmission rates.

Methods:
In this retrospective study, electronic medical records were reviewed for patients hospitalized for ischemic or hemorrhagic strokes at Kaiser Permanente San Francisco Medical Center between April 1, 2017 to March 31, 2023. Patients with a modified Rankin score of 3-5 were offered enrollment in the Stroke Transitions Program (intervention group). The control group included patients not enrolled in the program. The program involves telephone visits with a stroke-specialized nurse within 1 week after discharge and 3 months post-discharge. During the visits, the nurse promotes medication adherence, ensures follow up appointments are scheduled, screens for stroke related complications such as falls, spasticity, memory loss, and depression, and provides stroke education. Patients were also provided with the stroke nurse’s direct contact information to help navigate the healthcare system. Outcomes were 1 year hospital readmission rates by all-cause and due to repeat stroke.

Results:
Patients in the intervention group and control group were similar in age, BMI, race, smoking status, as well as rates of hypertension, diabetes, hyperlipidemia, atrial fibrillation, and history of prior stroke, with the exception of discharge rate to skilled nursing facility was higher in the intervention group (p=0.02). The intervention group had a significantly lower rate of 1 year hospital readmission due to any cause (62.1% vs 69.3%, p=0.04). The two groups did not differ significantly in 1 year hospital readmission rates due to repeat stroke.

Conclusions:
The implementation of the Stroke Transitions Program may have contributed to significantly reduced 1 year hospital readmission rates for stroke survivors, particularly considering that although more patients in the intervention group were discharged to a SNF which have higher hospital readmission rates, the intervention group showed significantly lower readmission rates.