bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP224: Timing of Ischemic and Hemorrhagic Stroke With Myeloproliferative Neoplasm Diagnosis Among Veterans
Authors: Mathur Natasha , Tiu Andrew , McKinnell Zoe , Gill Puneet , Antonio Martha , Liu Shanshan , Diao Guoqing , Subrahmanyam Ramesh , Kessler Craig , Jain Maneesh
Published: February 2024

Myeloproliferative Neoplasms (MPNs) are rare acquired stem cell disorders, consisting of Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF), complicated by thrombohemorrhagic events such as stroke. The timing of ischemic stroke (IS) and hemorrhagic stroke (HS) in relation to MPN diagnosis among Veterans remains undefined.

We utilized the Veterans Affairs Informatics and Computing Infrastructure database from 1/1/2006 - 1/26/2023 and included 586,555 Veterans from Illinois, the state most representative of the US population. ICD-9 and -10 codes identified Veterans with stroke and MPN. Fisher’s exact test was utilized to compare MPNs vs. non-MPNs.

There were 237 MPNs and 15,221 non-MPNs with IS while there were 26 MPNs and 1,567 non-MPNs with HS (Table 1). There were no differences in age of stroke diagnosis among MPNs vs. non-MPNs. There were higher rates of hypertension, smoking, and heart failure among MPNs vs. non-MPNs with IS.

Majority of IS was diagnosed either more than 3 months before MPN diagnosis (N=115, 48.5%) or more than 5 years after diagnosis (N=98, 41.4%). Among MPNs with HS, stroke was predominantly diagnosed (N=14, 53.8%) more than 3 months before and (N=7, 26.9%) within 3 months of MPN diagnosis (Figure 1). Among MPNs there was recurrence of stroke among 45.18% of IS and 40% of HS.

Although MPN are infrequent causes of stroke, these findings suggest continued surveillance for MPN and workup for driver mutations after a stroke diagnosis. This study also suggests consideration for dual antiplatelet therapy for MPNs with cardiovascular risk factors to prevent IS and a multidisciplinary approach between neurology and hematology.
Abstract TP228: Association of Dependent Cannabis Use in Patients With Chronic Liver Disease With Stroke Hospitalizations and Subsequent Mortality: A Nationwide Analysis
Authors: Guddeti Ananth V , Doshi Preet , Baskara Salian Rishabh , Gowda Supreeth N , Akella Sai Anusha , Shaik Mahboob Younus , Subarmani Shobana Lokeash , Faiz Haseeb , Kohli Muskan , Mahadevan Arankesh , Desai Rupak
Published: February 2024

Introduction:
Chronic liver disease (CLD) predisposes to systemic manifestations like thrombocytopenia and coagulopathy that can trigger stroke onset. Cannabis, due to its anti-inflammatory effects, could have a potential benefit for CLD patients. We aimed to study the impact of cannabis use disorder (CUD) or dependent use on stroke risk in CLD, considering recent American and Canadian surveys reporting 85% overlap between medicinal and recreational use.

Methods:
The National Inpatient Sample, 2019, was queried to identify adult stroke hospitalizations in patients with CLD. Two cohorts were created based on the presence of CUD. The primary outcomes were the rates and odds of stroke or acute ischemic stroke (AIS), with subsequent mortality in CUD vs. non-CUD cohorts. Secondary outcomes were resource utilization. Multivariable regression was controlled for patient-hospital-level factors and relevant comorbidities.

Results:
The CUD+ cohort had a lower rate of both overall stroke hospitalization (1.2% vs. 2.0%) and AIS hospitalization (0.8% vs. 1.2%) as compared to the CUD- cohort (p<0.001). The median age of admissions for stroke and CLD with CUD was 58 years, whereas it was 64 years in the non-CUD cohort. Traditional CVD risk burden was lower, but uncomplicated hypertension, PVD, prior MI, and drug abuse were more prevalent in the CUD+ cohort. Patients with CLD and CUD showed lower odds of any stroke (OR: 0.61, 95% CI: 0.51-0.73; p <0.001) and AIS (OR: 0.68, 95% CI: 0.55-0.85; p = 0.001) vs. the CUD- cohort. When adjusted for confounders, the odds of overall stroke risk were still lower (OR: 0.81; 95% CI: 0.66-0.98; p = 0.029) among the CUD+ cohort. However, adjusted odds for AIS showed no statistical significance (OR: 0.94; 95% CI: 0.74-1.19; p = 0.594). The all-cause mortality in the CUD+ cohort was lower compared to the CUD- cohort: 11.0% vs. 14.4%, p= 0.017, with shorter hospital stays and frequent routine discharges.

Conclusion:
This nationwide study revealed significantly reduced odds [20%] of stroke hospitalization in adults with CLD using cannabis on a regular, habitual basis. However, more prospective controlled studies are required to evaluate its impact on cardio-cerebrovascular risk with clarity on dose, duration, and mode of CUD in the long term.
Abstract TP23: Differentiated Para-Vascular Distribution of Amyloid Plaques in Normal versus Cognitively Impaired
Authors: Dumitrascu Oana M , Doustar Jonah , Koronyo Yosef , Fuchs Dieu-Trang , Torbati Tania , Sherman Dale , Black Keith , Lyden Patrick D , Koronyo-Hamaoui Maya
Published: February 2024

Introduction:
The vascular contribution to Alzheimer’s disease (AD) and AD-related dementias is increasingly recognized. Scanning laser ophthalmoscopy (SLO) visualizes two important markers of cognitive dysfunction in the retina, vascular changes and amyloid plaque deposition. The relationship between retinal vascular changes and peri-vascular amyloid deposition in the continuum of neurodegeneration is imperfectly understood. In this exploratory topographic analysis of a cohort of subjects with normal and impaired cognition that underwent SLO, we investigated the retinal vascular-adjacent (para-vascular) amyloid plaque distribution and its correlation with cognitive measures.

Methods:
34 subjects with cognitive decline underwent retinal SLO, brain magnetic resonance imaging and standard neuropsychometric testing. Retinal para-arteriolar and para-venular curcumin positive amyloid plaques were quantified in the supero-temporal retinal quadrant, in the first-, second- and third-order retinal vascular branches. The para-venous and para-arteriolar amyloid count were compared between patients with normal and impaired cognition, and their correlation with brain volumes and white matter hyperintensities was determined.

Results:
We analyzed retinal para-venous and para-arteriolar amyloid and vascular-structural parameters derived from 29 subjects, mean (SD) age 65(7), 48% female. Para-arteriolar plaque was higher than para-venular plaque in the entire cohort (p<0.0001). Secondary branch para-venular amyloid plaque count was higher in patients with impaired cognition, CDR ≥1 and MOCA ≤26. The para-arterial plaque count in the secondary branches significantly correlated with hippocampal volume and white matter hyperintensities scores.

Conclusion:
Our topographic analysis of the amyloid plaque distribution in retinal para-vascular regions shows higher amyloid accumulation in the para-arteriolar regions overall, and specifically in the secondary para-venular branches in patients with impaired cognition. Larger longitudinal studies are needed to study the temporal and spatial relationship between vascular dysfunction and para-vascular amyloid deposition in AD.
Abstract TP238: Blood Brain Barrier Injury Detected in the Serum of Patients With a History of Stroke and Transient Ischemic Attack
Authors: French Scott R , Arias Juan C , Bolakale-Rufai Ikeoluwapo K , Serrano Geidy E , Beach Thomas G , Reiman Eric M , Weinkauf Craig C
Published: February 2024

Introduction:
Stroke and transient ischemic attack (TIA) increase risk for cognitive impairment and dementia. Without a lasting infarction, the cause of cognitive decline after TIA remains unknown. We hypothesize that these cerebrovascular accidents (CVAs) have long-term negative effects on the blood brain barrier (BBB) and promote endothelial inflammation, both of which are associated with neurodegeneration. We sought to investigate the effects of CVAs on BBB integrity and endothelial inflammation by evaluating PDGFRβ and VCAM-1 serum levels, respectively.

Methods:
A subset of 88 subjects in the Arizona Study of Aging and Neurodegenerative Disorders with postmortem serum samples were available for analysis. Sandwich ELISA was performed to detect PDGFRβ and VCAM-1. Statistical analyses were performed using Spearman’s rank correlation and Mann Whitney U test.

Results:
Our subjects were split based on CVA status and matched according to vascular risk factors. Both subjects with stroke and subjects with TIA had increased serum PDGFRβ compared to those without history of CVA (6608.4 pg/mL and 5337.0 pg/mL, P=0.04, and 7849.5 pg/mL vs. 5337.0 pg/mL, P<0.01). No significant differences related to PDGFRβ were observed between subjects with stroke vs. TIA (P=0.25). PDGFRβ was associated with VCAM-1 (Spearman’s r=0.44, P<0.01) and VCAM-1 trends towards being higher in subjects with CVA compared to those without (P=0.13).

Conclusions:
PDGFRβ was elevated in subjects who had a history of stroke or TIA compared to matched patients without CVA. These data demonstrate the utility of a serum-based biomarker of BBB integrity, a powerful tool in studying the role of the BBB in various neurodegenerative diseases including Alzheimer’s dementia. These data also raise the possibility that TIA and stroke have lasting effects on BBB integrity and provide insight about their mechanistic role in neurodegeneration. These findings are limited by our small sample size and post-mortem serum collection; still more, these promising serum biomarkers need further validation.
Abstract TP240: Safety of Dabigatran in Patients With Acute Minor Non-Cardioembolic Ischemic Stroke or Transient Ischemic Attack and Cerebral Microbleeds: A Post Hoc Analysis of the DATAS-II Randomized Trial
Authors: Balali Pargol , Butcher Ken , Ng Kelvin K , Joundi Raed A , Benavente Oscar , Katsanos Aristeidis , Sharma Mukul A , Shoamanesh Ashkan
Published: February 2024

Introduction:
Cerebral microbleeds are reported to predict risk of hemorrhagic transformation (HT) in patients with acute ischemic stroke. We aimed to investigate whether the effect of dabigatran (vs. aspirin) in patients with acute minor non-cardioembolic ischemic stroke/TIA is modified by baseline microbleeds on MRI.

Methods:
This is a post hoc analysis of the DATAS-II trial that randomized 305 patients with acute minor non-cardioembolic ischemic stroke/TIA to dabigatran (150/110 mg twice daily) or aspirin (81 mg daily) for 30 days. MRIs of patients with T2*-weighted sequences on their baseline scans underwent blinded central adjudication for microbleeds.

Results:
A total of 251 participants (mean age=66±13 years, 36% women, median [IQR] time from symptom onset to randomization 40 [27-55] hours; mean NIHSS=1.5±1.9) were included in these analyses, of whom 82 (33%) had baseline microbleeds. On 30-day MRI, 6% (n=14) developed HT, and 80% (n=191) achieved mRS 0-1 at 90 days. In multivariable logistic regression analyses, we found no association between microbleeds and HT (adjusted odds ratio [aOR], 0.76; 95% CI, 0.18-3.23) on 30-day MRI or mRS 0-1 at 90 days (aOR, 1.54; 95% CI, 0.70-3.41). The rates of HT and mRS 0-1 in patients with microbleeds were 3% on dabigatran and 4% on aspirin (OR, 0.71; 95% CI, 0.06-8.17), and 74% on dabigatran and 84% on aspirin (OR, 0.54; 95% CI, 0.18-1.64), respectively. The presence, severity, or location of microbleeds did not modify the effect of dabigatran on these outcomes (p-interaction>0.05).

Conclusions:
Early dabigatran treatment appears safe in patients with acute minor non-cardioembolic ischemic stroke/TIA and hemorrhage-prone cerebral small vessel disease marked by microbleeds on MRI.
Abstract TP242: Predictive Validity of the Modified World Federation of Neurosurgical Societies Subarachnoid Hemorrhage Grading System (Modified WFNS Scale) for the Outcome of Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Luong Chinh Q , Nguyen Tuan A , Mai Ton D , Vu Luu D , Ngo Hung M , Hoang Hai B , Tran Tuan A , Pham Trang Q , Pham Dung T , Nguyen My H , Nguyen Linh Q , Dao Phuong V , Nguyen Duong N , Vuong Hien T , Vu Hung D , Nguyen Dong D , Vu Thanh D , Nguyen Dung T , Do Anh L , Nguyen Cuong D , Do Son N , Nguyen Hao T , Nguyen Chi V , Nguyen Anh D , Dao Co X
Published: February 2024

Introduction:
Evaluating the prognosis of aSAH patients who may be at risk of poor outcomes using grading systems is one way to make a better decision on treatment for these patients. This study compared the accuracy of modified WFNS, WFNS, and Hunt and Hess (H&H) scales in predicting the aSAH patient's outcome.

Methods:
From August 2019 to June 2021, we conducted a multicenter prospective cohort study on aSAH adult patients in three central hospitals in Hanoi, Vietnam. The primary outcome was the 90-day poor outcome, measured by scores of 4-6 on mRS. We calculated areas under the receiver operator characteristic (ROC) curve (AUROCs) to determine how well the grading scales could predict patient prognosis upon admission. We also used ROC curve analysis to find the best cut-off value for each scale. We made comparisons of AUROCs using Z-statistics and compared 90-day mean mRS scores among intergrades using the pairwise multiple-comparison test. Finally, we used logistic regression to identify factors associated with the 90-day poor outcome.

Results:
Of 415 patients, 32% had a 90-day poor outcome. Modified WFNS (AUROC: 0.839 [95% CI: 0.795-0.883]; cut-off value≥2.50), WFNS (AUROC: 0.837 [95% CI: 0.793-0.881]; cut-off value≥3.5), and H&H scales (AUROC: 0.836 [95% CI: 0.791-0.881]; cut-off value≥3.5) were all good at predicting patient prognosis on day 90th after ictus. However, there were no significant differences between AUROCs of these scales. Only grades IV and V of modified WFNS (3.75±2.46 vs. 5.24±1.68, p=0.026), WFNS (3.75±2.46 vs. 5.24±1.68, p=0.026), and H&H scales (2.96±2.60 vs. 4.97±1.87, p<0.001) showed a significant difference in the 90-day mean mRS scores. In the multivariable models, with the same set of confounding variables, modified WFNS grade of III-V (adjusted OR (AOR): 9.090; 95% CI: 3.494-23.648) was more strongly associated with increased risk of the 90-day poor outcome compared to WFNS grade of IV-V (AOR: 6.383; 95% CI: 2.661-15.310) or H&H grade of IV-V (AOR: 6.146; 95% CI: 2.584-14.620).

Conclusions:
In this study modified WFNS, WFNS, and H&H scales all had good discriminatory abilities for the prognosis of aSAH patients. Because of better effect size in predicting poor outcomes, the modified WFNS scale seems preferable to the WFNS and H&H scales.
Abstract TP260: Association Between Cerebral Small Vessel Disease and Prehospital Delay in Acute Ischemic Stroke
Authors: Masui Marina , Sato Takeo , Okumura Motohiro , Ishikawa Takahiro , Kokubu Tatsushi , Takahashi Junichiro , Kitagawa Tomomichi , Tanabe Maki , Onda Asako , Komatsu Teppei , Sakuta Kenichi , Sakai Kenichiro , Umehara Tadashi , Mitsumura Hidetaka , Iguchi Yasuyuki
Published: February 2024

Objective:
To elucidate whether the severity of cerebral small vessel disease (SVD) is associated with the prehospital delay in acute ischemic stroke.

Methods:
Consecutive ischemic stroke patients admitted to our hospital were screened. Inclusion criterion was: onset to door time within 14 days. Exclusion criteria were: in-hospital onset stroke, and patients without an MRI scan. We evaluated SVD burden using the total SVD score defined as a sum of the following four items (maximum score 4): old lacunes, cerebral microbleeds, basal ganglia enlarged perivascular spaces (EPVS), and white matter hyperintensity. EPVS severity was classified as follows; grade 0 = no EPVS, grade 1 = 1-10 EPVS, grade 2 = 11-20 EPVS, grade 3 = 21-40 EPVS, and grade 4 = 41 or more EPVS. Patients were divided into two groups, onset to door time within 4.5 hours (early arrival group) and over 4.5 hours (delayed arrival group). First, we assessed whether the total SVD score could be related to the two groups using logistic regression analysis. Second, we assessed which item of the total SVD score was independently associated with the prehospital delay. Finally, we checked if that item had a linear association with the prehospital delay.

Results:
We screened 2,112 patients, including 1,754 (1,253 (71%) male, median age 69 years). Of all, 1,105 patients (63%) were included in the delayed arrival group. The total SVD score was independently associated with the prehospital delay (OR 1.11, 95% CI 1.01-1.21,
p
=0.025). Among the four items, only EPVS was independently associated with the prehospital delay (OR 1.37, 95% CI 1.05-1.80,
p
=0.022). A linear trend was observed between EPVS grades and the prehospital delay in reference to EPVS grade 0-1 (EPVS grade 2: OR 1.22, 95% CI 0.92-1.62,
p
= 0.170, EPVS grade 3: OR 1.69, 95% CI 1.20-2.38,
p
= 0.002, EPVS grade 4: OR 2.17, 95% CI 1.37-3.44,
p
= 0.001, Figure).

Conclusions:
Prehospital delay in acute ischemic stroke could be associated with SVD, especially basal ganglia EPVS.
Abstract TP262: Trends, Odds, Burdens and Outcomes of Metabolically Healthy Obesity in Stroke Related Hospitalizations of Elderly Patients - A Nationwide Analysis, 2016-2019
Authors: Doshi Preet , Kohli Muskan , Baskara Salian Rishabh , Gowda Supreeth N , Akella Sai Anusha , Shaik Mahboob Younus , Subarmani Shobana Lokeash , Faiz Haseeb , Raghavan Pavithra , Guddeti Ananth V , Desai Rupak
Published: February 2024

Background:
Obesity has been associated with an increase in the risk of stroke and poor outcomes. Meanwhile, Metabolically healthy obesity (MHO) trends are understudied in association with stroke. In this study, we aim to analyze the MHO trends and outcomes with respect to Stroke.

Methods:
We queried the National Inpatient Sample (2016-2019) to identify Stroke hospitalizations in the elderly population (%E2%89%A565 years) with vs without MHO by using ICD-10 codes after excluding patients with Hypertension, analyze, and Diabetes Mellitus. Patients were categorized into a metabolically healthy obese MHO+ve cohort, BMI> 30, and MHO-ve cohort, BMI<30. Trends, demographics, comorbidities, and outcomes were then compared between the two cohorts.

Results:
Overall Prevalence of stroke was higher in the MHO-ve cohort (2.4% vs 1.4% p<0.001) compared to the MHO+ve cohort. MHO-ve cohort often consisted of higher median age (78 vs 73 years), Males (48.2% vs 36.4%), Hispanics (5.1% vs 4.7%), whites (83.8% vs 82.3%), Asians (2.4% vs 1.1%) vs MHO +ve cohort (p<0.001). The rate of death (15.9% vs 14.4%), Home health care requirements (16.6% vs 12.4%) was also higher in the MHO-ve cohort vs MHO+ve cohort. Conversely, the MHO+ve cohort had higher rates of smokers, Prior MI, Hypothyroidism, CKD, and OSA in comparison to the MHO-ve cohort. Univariate and Multivariate regression analysis adjusted for confounders did not show any significant association between Stroke and MHO.

Conclusion:
Excluding other cardiovascular disease risk factors such as hypertension, diabetes mellitus, and hyperlipidemia, the non-significant difference in in-hospital mortality between elderly stroke patients with vs without MHO suggests that MHO might not be a significant independent predictor of short-term mortality. Other factors likely influence this relationship. Further research is warranted for the investigation of the factors influencing the absence of a relationship between stroke and MHO.
Abstract TP264: Does Cerebral White Matter Disease Predict Post-Stroke Fatigue or Depression in an Afro-Caribbean Cohort?
Authors: Solis Ramirez Jonathan , Mulatu Yohannes , Gilles Nadege , Levine Steven R
Published: February 2024

Background and Purpose:
Fatigue and depression frequently occur after ischemic stroke and are associated with worse Health-Related Quality of Life. While there has been research on the correlation between the burden of white matter disease (WMD) and the onset of depressive symptoms, this relationship has yet to be validated in patients with stroke from minority groups.

Methods:
An IRB-approved retrospective, cross-sectional study. The study sampled a cohort of patients aged ≥18 years old who had stroke within the last 3 years and were assessed with standardized questionnaires for fatigue (Fatigue Assessment Scale [FAS], score range 10-50) and depression (Beck’s Depression Inventory, score range 0-63). Exclusion criteria included patients with prior depression or severely disabling pre-existing conditions that would confound assessment. Patients with available MRI were evaluated using the Fazekas scale (score range 0-3), a validated visual scale (correlates significantly with automated software), to grade WMD. Grading was conducted blinded to patient's fatigue and depression scores. The collected ordinal data presented a non-parametric distribution thus was analyzed using the Spearman correlation coefficient.

Results:
Of 72 patients with available MRI, 96% identified as African or Caribbean; mean age = 66, median FAS score = 19 (IQR 14-26), and median BDI score = 6 (IQR 2-11). The prevalence of stroke-related disability (modified ranking scale ≥ 2) was 38%. Within the Fazekas grading, the score was 0 in 12.4%, 1 in 41.4%, 2 in 31.7%, and 3 in 13.8%. Spearman correlation coefficients showed non significant associations between WMD severity and either depression (

R
s

=0.058, p=0.62, 95%CI -0.17,0.29) or fatigue (

R
s

=0.059, p=0.62, 95% CI -0.18,0.30).

Conclusion:
Our results suggest no association between WMD severity and the development of post-stroke fatigue or depression in an Afro-Caribbean population. However, the lack of statistical significance might be due to limited sample size and patient heterogeneity, since few patients exhibited high scores for fatigue and depression. Additional studies are needed to validate the absence of correlation.
Abstract TP271: A Retrospective Analysis of Demographic and Clinical Variables Within a Single Center Young Stroke Cohort
Authors: Ford Thomas , Scott Alexander , Shulman Julie G
Published: February 2024

Introduction:
Despite significant efforts to increase public awareness of cerebrovascular disease, the incidence of stroke and transient ischemic attack (TIA) in young adults has remained elevated, representing a major public health concern. We sought to better characterize our young stroke population in order to gain insight as to where targeted interventions could be beneficial in community outreach and support of affected patients.

Methods:
We conducted a retrospective study evaluating young adults (under 50 years of age) presenting to a single urban academic medical center with acute ischemic stroke or TIA between 2013 and 2022. Demographic information and clinical variables (including past medical history, Trial of Org 10172 in Acute Stroke Treatment [TOAST] classification of stroke etiology, and discharge disposition) were extracted from the electronic medical record and descriptive statistics were calculated.

Results:
A total of 408 patients were reviewed. Within this study population, the median age was 43 years (IQR 38-47 years) and 235 (57.6%) were men. The median initial National Institutes of Health Stroke Scale upon presentation was 3 (IQR 1-7). The most common stroke risk factors were tobacco use (44.6%), pre-existing cardiovascular disease (26.2%), and other substance use (23.8%). The most common TOAST classification upon discharge was Stroke of Undetermined Etiology (32.9%). Most patients (244, 59.8%) were discharged directly to home from the hospital, although 140 (34.3%) were transitioned to another facility, including acute rehabilitation facilities (95, 23.3%), skilled nursing facilities (22, 5.4%), and long-term acute care hospitals (11, 2.7%).

Conclusion:
Our study highlights that the continued high incidence of stroke in the young may be at least partially attributable to a high prevalence of traditional cardiovascular risk factors, thus emphasizing the importance of smoking cessation counseling and early treatment of hypertension in the primary care setting. In addition, while most young patients will present with minor stroke symptoms, a significant portion are unable to return directly to home upon discharge from the hospital.
Abstract TP273: Misdiagnosis of Pregnancy-Associated Stroke in the Emergency Department
Authors: Salehi Omran Setareh , Zhang Cenai , Parikh Neal S , Seitz Alison , Kamel Hooman , Navi Babak B , Liberman Ava L
Published: February 2024

Introduction:
Pregnancy and the postpartum period are associated with an increased risk of ischemic and hemorrhagic strokes. The incidence of missed or delayed diagnosis of pregnancy-associated stroke in the emergency setting is unknown.

Methods:
We conducted a retrospective cohort study of all women aged 12 years or older who were hospitalized for labor and delivery using deidentified administrative claims data from all nonfederal EDs and hospitals in New York from 2006-2016 and Florida from 2005-2018. In this cohort, we then identified women hospitalized for a cerebrovascular event (either ischemic or hemorrhagic stroke) using previously validated
ICD-9-CM
or
ICD-10-CM
codes during a 270-day period extending from 6 months before through 3 months after delivery. We defined probable ED misdiagnosis of stroke as having an ED treat-and-release visit for neurological complains (e.g., headache, dizziness, numbness) within the 14 days preceding their stroke hospitalization. Logistic regression was used to compare rates of clinical outcomes in pregnant or postpartum stroke patients with and without probable stroke misdiagnosis after adjusting for demographic and vascular risk factors.

Results:
Among 3,474,960 women hospitalized for labor and delivery, 350 (0.01%) were hospitalized for an ischemic or hemorrhagic stroke during the study period. Out of the 350 pregnant or postpartum women hospitalized for stroke, 17 (4.9%; median age 30) had at least one preceding ED visit for a neurological symptom (probable misdiagnosis). There was no difference in length of stay (4 versus 5 days, p = 0.97), mortality (0% versus 3.6%, p = 1.00), and discharge to home (70.6% versus 57.1%, p = 0.27) after stroke hospitalization between patients with versus without a probable ED misdiagnosis.

Conclusion:
Probable ED misdiagnosis occurred in nearly 1 of 20 cases of pregnancy-associated stroke in a large, multistate cohort. However, misdiagnosis was not associated with increased length of stay, higher mortality, or lower rates of discharge to home after stroke.
Abstract TP276: AF Detection on Zio-Patch is Higher in ESUS vs. Non-Cardioembolic Stroke Subtype
Authors: Chang Jason , Shu Liqi , Goldstein Eric , Furie Karen L , Yaghi Shadi
Published: February 2024

Background:
Clinical trials showed that the paroxysmal occult AF is detected in 30% of patients with cryptogenic stroke on insertable cardiac monitors but recently the STROKE-AF trial showed a similar rate in patients with non-cardioembolic stroke, thus questioning the significance of device detected AF as a cause of the ischemic stroke. In this study, we aim to compare AF detection rates in patients with ESUS compared to those with non-cardieombolic stroke mechanisms on ZIOPATCH monitoring.

Methods:
We analyzed data of patients with acute ischemic stroke who had a two-week ZIOPATCH monitor placed post stroke over a 2 year period. We collected data on demographics, risk factors, and ZIOPATCH findings in all patients. Stroke subtype was categorized based on the TOAST criteria into small vessel disease, large artery atherosclerosis, stroke of other determined mechanism, and cryptogenic stroke. Cryptogenic stroke was defined based on the ESUS criteria. AF was abstracted from the ZIOPATCH report and confirmed by the reviewing physician. We determined association between stroke subtype (ESUS versus non-cardioembolic stroke) and AF detection using multivariable models.

Results:
Over the study period, we identified 239 patients discharged with a diagnosis of acute ischemic stroke who underwent cardiac monitoring via a 2-week ZIOPATCH with a median of 13 days of monitoring; 116 (49%) were ESUS and 65 (27%) were classified as large artery atherosclerosis and 19% were classified as small vessel disease. AF was detected 3.3% (8/239) of patients. In univariate analyses, patients with ESUS were more likely to have AF compared to non-cardieombolic stroke (6.0% vs. 0.8%, p = 0.032). In an adjusted model controlling for age, patients with ESUS were more likely to have AF detected on ZIOPATCH (aOR 7.53, p = 0.06).

Conclusions:
Paroxysmal occult AF detected on a 2-week ZIOPATCH is more likely to occur in ESUS vs. non-cardioembolic suggesting a mechanistic association with cardioembolism.
Abstract TP278: Identifying High-Risk Patients With Poor Prognosis in Acute Phase of Ischemic Stroke: Treatment-Specific Risk Scales Developed From the National Neurological Medical Center of China
Authors: Xu Yi , Han Xiang
Published: February 2024

Background:
There is still a lack of acute ischemic stroke (AIS) prognostic prediction scales to assist in more scientific and efficient clinical management of patients.

Objective:
Real-world data were utilized to construct and validate an easily popularized prediction score for poor prognosis in the acute phase of AIS so as to provide a basis for clinical monitoring and intervention of specific indicators.

Method:
Patients discharged from Huashan Hospital, Fudan University between 2015 and 2021 were consecutively included. AIS with premorbid mRS ≤ 2 within 72 hours of onset was included. Patients treated with arterial thrombectomy were excluded. Subjects were divided into "intravenous thrombolysis group" and "non-intravenous thrombolysis group". Based on the data of discharge patients from 2015 to 2020 (Model Training Set), logistic regression model with restricted cubic splines were applied to construct the "prognostic scale of AIS acute stage based on treatment stratification, PAIST Scale". Performance of the scale was tested using the area under the receiver operating characteristic curve (AUC-ROC) based on data from patients discharged in 2021 (External Validation Set).

Result:
A total of 1971 patients (437 thrombolysis) were included. The "PAIST Scale" of the thrombolysis patients included: Baseline NIHSS (5-15 = 11, ≥ 16 = 20), deep vein thrombosis (yes = 5), Neuron specific enolase (> 13 ng/ml = 3), and neutrophil percentage (> 70% = 5). The "PAIST Scale" of the Non-thrombolytic population: Baseline NIHSS (5-15 = 12, ≥ 16 = 20), deep venous thrombosis (yes = 4), Neuron specific enolase (> 12.5 ng/ml = 1), neutrophil percentage (> 66% = 3), age (> 64y = 2), fasting blood glucose (> 5.8 mmol/l = 2), serum potassium (< 3.8 mmol/L = 1). In the external validation set, the AUC-ROC values of "PAIST Scale" were 0.855 in the non-thrombolysis group and 0.778 in the thrombolysis group. Meanwhile, patients defined as high-risk by the "PAIST scale" had an actual incidence of poor prognosis of 76.92% in the thrombolysis group (> 19 points) and 61.11% in the non-thrombolysis group (> 17 points).

Conclusion:
The "PAIST Scale" established in this study can effectively identify patients at high risk of poor prognosis in the acute phase among patients with mild to moderate stroke.
Abstract TP299: The Relationship Between Intracranial Arterial Stenosis Rate and Cerebral Perfusion
Authors: Qin Haiqiang , Liu Gaifen , Wang Anxin , Zhang Yijun , Anqi Wang
Published: February 2024

Background and and Objectives:
The pressure ratio (PR) across lesions is a vital indicator for assessing residual blood flow after stenosis, yet the relationship between symptomatic intracranial atherosclerotic stenosis degrees and cross-lesion pressure ratios remains unclear.

Methods:
Data were derived from the Chinese National Stroke Registry III (CNSR III). Three-dimensional meshes were constructed based on TOF-MRA using the finite element method controlled by the Navier-Stokes equation to obtain pressure values. PR was calculated as the ratio of proximal to distal pressure at the stenosis site, indicating post-stenosis blood flow. PR > 0.76 meant normal pressure ratio, while PR ≤ 0.76 indicated reduced ratio. Arterial stenosis severity was categorized using the WASID

Method:
50%-69% for moderate and 70%-99% for severe. Statistical analysis explored the correlation between stenosis severity and low PR.

Results:
The study included 438 patients with symptomatic intracranial arterial stenosis (50-99%), median age 64, 33.79% female. PR ≤ 0.76 accounted for 30%. Among them, PR ≤ 0.76 was observed in 26% of moderate stenosis (50-69%) patients and 39% of severe stenosis (70-99%) patients (Figure A). The PR ≤ 0.76 frequency was significantly higher in severe compared to moderate stenosis (P=0.01). For anterior (Figure B) and posterior (Figure C) circulation stenosis, PR ≤ 0.76 accounted for 43% and 22% respectively, more prevalent in severe stenosis (P=0.01 and P=0.61, respectively).

Conclusion:
Most patients with symptomatic intracranial atherosclerotic stenosis exhibit normal PR levels, with a correlation between arterial stenosis and cross-lesion pressure ratio. Further research is needed to determine if PR is a more suitable criterion than arterial stenosis for selecting patients for stent treatment.
Abstract TP300: Apolipoprotein-E Deficiency and High Fat Diet Alter Immunomodulatory Cellular and Molecular Determinants Promoting Atherosclerosis, a Stroke Risk Factor
Authors: Wesley Umadevi V , Bora Ragini , Ricks Katherine , Nelson Dylan , Sutton Ian , Chao Olivia , Aziz Maximos , Dempsey Robert J
Published: February 2024

Background:
Most ischemic strokes are caused by atherosclerosis. Atherosclerotic plaque formation is modulated by genetic and environmental interactions. Apolipoprotein E (ApoE) regulates lipid metabolism, and its deficiency is associated with dyslipidemia and atherosclerosis. ApoE is abundantly expressed in glial cells and neurons of the brain, affecting the blood brain barrier and cognitive function. Poor dietary habits promote the onset of atherosclerosis. In this study, we examined the effects of ApoE deficiency and high fat diet (HFD) on plaque formation and immunomodulatory cellular and molecular mechanisms in mice models.

Methods:
Wild type and ApoE knockout (KO) mice were fed with normal or HFD. Carotid plaques were examined using hematoxylin and eosin staining. Targeted proteomic profiling identified the circulating inflammatory proteins. Pathway specific transcriptomic profiles were identified using PCR arrays and real-time PCR. Immunohistochemistry assays were done in brain sections using a neuronal marker (NeuN), an astrocyte marker (GFAP) and a microglia marker (Iba1). The expression of Pentraxin-3 (PTX3), lipocalin2, and PAI-1 were examined using immunohistochemistry. Images were acquired and analyzed using a Keyence fluorescence microscope and NIH ImageJ.

Results:
ApoE deficiency and HFD enhanced atherosclerotic plaque formation as a function of age in association with a significant increase in circulating pro-inflammatory cytokines in blood/plasma, including M-CSF, C-reactive protein, and PTX3. The number of microglial cells and astrocytes was increased with altered morphology in ApoE KO and aged animals’ brain cortex and dentate gyrus. Whereas neuronal cell number was decreased in the brains of ApoE deficient and aged mice. The mRNA levels of SELE, PAI-1, lipocalin2, and PTX3 were upregulated in ApoE deficient and WT animals fed with HFD. Higher levels of PTX3 were also observed in atherosclerotic plaques.

Conclusion:
ApoE deficiency and HFD may play a key role in altering immunomodulatory cellular responses and initiating pro-inflammatory molecular signaling. These events may promote atherosclerotic plaque formation, a risk factor for ischemic stroke and worsen brain damage.
Abstract TP31: Identifying Multivariate Nonlinear Bias in Sammpris Using Graph-Based AI Analysis
Authors: Scalzo Fabien , Liebeskind David S , Hinman Jason D , Seyedzadeh Aleena
Published: February 2024

Background:
Clinical trials are the most rigorous way of testing how novel treatments compare with existing ones regarding outcomes. The randomized controlled clinical trial has become the standard means of providing proof of safety and effectiveness across the board in medicine, including stroke. Yet, the risk factors among patients that are randomized might not always be equally distributed such that a bias may occur. In this study, we focus on the SAMMPRIS clinical trial aimed to assess the safety and efficacy of aggressive medical management versus stenting for preventing recurrent stroke in patients with symptomatic intracranial arterial stenosis.

Methods:
We developed and evaluated a machine learning model to identify potential multivariate bias present in the dataset that could not have been identified using standard statistical tests. Our approach utilizes a machine learning model based on the spectral regression model (SR-KDA) to identify biases created by combinations of variables. SR-KDA is based on a graph representation of the data that is processed via discriminative analysis to identify groups of patients that share common characteristics. By using both the treatment and outcome variables as constraints, the model is able to identify nonlinear relationships between clinical variables and the outcome. It can also be used to identify bias as part of the randomization that could have inadvertently skewed the statistical results with standard methodologies.

Results:
Our approach was successfully applied to the SAMMPRIS clinical dataset, which includes 121 clinical variables. The algorithm was able to automatically identify 6 clusters of patients that had a different response to treatment when considering the clinical variables. Each group was then assigned a set of the variables' cut-off values that best describe them.

Conclusion:
We have developed a sophisticated system that is capable of detecting non-linear correlations in clinical data collected during trials. This solution has the potential to mitigate any biases that may arise during the randomization process, which could ultimately improve recruitment efforts. Moving forward, this innovative tool could be applied proactively to future clinical trials.
Abstract TP311: Preclinical Replication Study of Psd-95 Inhibitor NA-1
Authors: Kim Ha , Choi Seungbum , Kim Dong-Eog
Published: February 2024

Background & Objective:
Nerinate (NA-1), a postsynaptic density protein-95 inhibitor, is a clinical-stage stroke neuroprotectant. Recently, in a phase-III clinical trial (Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke [ESCAPE-NA1]), a single intravenous dose of NA-1 did not improve the proportion of patients achieving favorable 3-month functional outcomes after endovascular thrombectomy compared with patients receiving placebo. Thus, we conducted a preclinical replication study to test therapeutic efficacy of NA-1 in a mouse model of transient middle cerebral artery occlusion (tMCAO).

Methods:
After 30-minute or 60-minute MCAO with laser Doppler flowmetry (LDF) monitoring, mice were randomly assigned to a group treated with either vehicle control (n=10 and 21, respectively) or 10 nM/g NA-1 (n=10 and 21, respectively), which was intravenously administered once via penile vein in a volume of 200 μL at the beginning of recanalization. In a different set of mice (n=6 for vehicle and n=6 for NA-1), we performed MCAO and then allowed animals to wake up before reperfusion at 60 minutes to account for continuous anesthesia-related confounding. At 1-day poststroke, brain was harvested and sliced in 2-mm thickness for 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and infarct volume measurement after neurological scoring.

Results:
LDF data indicated that stroke modeling was executed proficiently, without inter-group differences. The vehicle group and the NA-1 group showed similar infarct volumes at 1 day after either 30 minutes (32.5±6.4 mm
3
and 44.7±8.7 mm
3
; t-test
P
=0.27) or 60 minutes of MCAO (113.4±7.6 mm
3
and 108.2±7.6 mm
3
;
P
=0.63). Awakening between occlusion and reperfusion did not change the negative

Results:
109.4±11.7 mm
3
and 115.8±10.6 mm
3
(
P
=0.69). Neurological scores did not show significant inter-group differences, either (all
P
>0.05).

Conclusions:
We were unable to reproduce neuroprotective effects of NA-1 to reduce infarct volume at 1 day after tMCAO for 30 or 60 minutes. We suggest that implementation of multicenter animal studies is warranted to enhance the reproducibility and generalizability of preclinical observations.
Abstract TP312: Pharmacologically Reducing Acetylated Tau Prevents Traumatic Brain Injury-Induced Acceleration of Alzheimer’s Disease
Authors: Barker Sarah , Vazquez-Rosa Edwin , Shin Min-Kyoo , Caradonna Salvatore , Kornblit Ryan , Apostolakis Aristotle , Corella Sofia , Chaubey Kalyani , Franke Kathryn , Cintron-Perez Coral , Sridharan Preethy , Gan Li , Pieper Andrew
Published: February 2024

Traumatic brain injury (TBI) afflicts 70 million people worldwide annually and is the 3rd overall risk factor for developing Alzheimer's disease (AD), behind genetics and aging. In patients with AD, a history of TBI is associated with a 3-4 year earlier onset of cognitive impairment. TBI and AD share many pathologies, including blood brain barrier dysfunction, neuroinflammation, and protein aggregation. Yet, the underlying mechanism of this relationship is not understood, and there are no treatments that protect patients from accelerated AD after TBI. We recently reported that tau, a microtubule binding protein essential for neuronal health, is acetylated after TBI. Acetylation impairs tau binding to microtubules, leading to its mis-localization into the cell soma and pathological aggregation. Acetylated tau is also elevated early in AD, and acetylated tau was significantly more elevated in the brains of human AD subjects with a history of TBI, compared to AD alone and healthy controls. Therefore, we hypothesize that TBI-induced tau acetylation drives the acceleration of AD. To study this phenomenon, we developed a mouse model of TBI that accelerates AD-like pathology and cognitive impairment in 5xFAD mice, and amyloid-driven AD model. Our unique model of multimodal TBI produces a complex and reproducible brain injury with neurodegeneration and neurobehavioral impairment, beginning with acute axonal degeneration and persisting chronically with blood-brain barrier degradation and nerve cell death. This model of TBI also produces the same systemic metabolic alterations that are reported in TBI patients. TBI causes learning deficits in young 5xFAD mice that are not seen in either sham-injured 5xFAD mice or in wild type littermates subjected to TBI. TBI also accelerates amyloid deposition in 5xFAD mice. We hypothesize that TBI will also worsen blood brain barrier function in 5xFAD mice. Importantly, 5xFAD mice show greater elevation of acetylated tau after TBI, compared to WT mice. Preliminary data suggests that treatment with the FDA-approved non-steroidal inflammatory drug diflunisal, which inhibits the enzyme that acetylates tau, reduces acetylated tau and rescues behavior deficits after TBI in 5xFAD mice.
Abstract TP32: Sirtuin 3 Regulation of Mitochondrial Dynamics and Neuronal Apoptosis During Ischemia/Reperfusion
Authors: Chandran Sanjana , Sanderson Thomas H
Published: February 2024

Ischemic stroke occurs when the blood supply to the brain is interrupted, reducing the access of affected tissue to oxygen and glucose. The lack of oxygen inhibits the electron transport chain, leading to intracellular ATP deficiency, cellular damage, and death. The restoration of blood flow, known as reperfusion, allows the reintroduction of oxygen but may cause increased oxidative stress, as it hyperactivates the electron transport chain and thus induces excessive production of reactive oxygen species (ROS), leading to further cell death. One potential therapeutic target for reperfusion injury is Sirtuin 3 (SIRT3), which mediates the deacetylation of enzymes that are responsible for the reduction of ROS, leading to protection against oxidative stress. This study aims to understand the role of SIRT3 on ischemia and reperfusion-induced neuronal apoptosis. Primary neurons were isolated from wildtype mice postnatal day 0-1 and cultured for 14 days. The neurons underwent 2-hour oxygen-glucose deprivation mimicking stroke, followed by reperfusion. The neurons were then lysed, and western blots were done to analyze changes in protein levels. The western blots show that SIRT3 levels significantly decline over 1-6 hours post-reperfusion (n≥3, p<0.05), and TOM20, a mitochondrial protein, declines at 1 hour post-reperfusion(n≥3, p<0.05), indicating mitophagy. In addition, the cleavage of caspase-3 significantly increases at 4 hours post-reperfusion (n=3, p<0.05), implying apoptosis. Our data suggests that SIRT3 plays a crucial role in the mitochondrial metabolism of neurons and could be a potential target for reperfusion therapy. Future experiments would examine the effects of a SIRT3 activator and inhibitor on cell apoptosis.
Abstract TP35: A 2-Stage Recruitment Design to Reduce MRI Screening Costs for a Theoretical Clinical Trial of WMH Progression
Authors: Egle Marco , Power Melinda , Deal Jennifer A , Jack Clifford R. , Sullivan Kevin J , Mosley Thomas H , Gottesman Rebecca F
Published: February 2024

Background:
White matter hyperintensities (WMH) are associated with risk of dementia and stroke, so are an important therapeutic target for clinical trials. The cost of broad MRI screening to identify those individuals with significant WMH, however, limits the feasibility of designing clinical trials which target WMH presence and which test treatments that slow progression.

Hypothesis:
A low-cost retinal or clinical screening measure prior to an MRI screening stage reduces the cost of recruiting persons with significant WMH burden in a hypothetical clinical trial vs an MRI-only screening design.

Method:
Data were from participants in the Atherosclerosis Risk in Communities-Neurocognitive study with clinical, retinal and WMH measurements (
N
= 1311) at ages 53-70 years. Significant WMH burden was defined as a Cardiovascular Health Study score >2. Three low-cost pre-screening measures were assessed: (1)
retinal:
a score incorporating multiple markers of abnormal retinal vasculature, (2)
clinical:
a score incorporating hypertension, diabetes, and age, (3)
combined retinal-clinical:
a score incorporating retinal and clinical factors. Given a prior published target sample for a WMH clinical trial (N= 646), we calculated a theoretical screening sample size based on the proportion of each pre-screening measure in the population multiplied by the proportion of significant WMH burden among those with a prevalent pre-screening feature. Total recruitment cost was calculated using standard retinal ($32.50) and MRI ($650) cost estimates.

Results:
Compared to the estimated cost of MRI-only screening (>$4.24M, requiring MRI screening 6,526 participants), pre-screening for a high clinical score reduced total cost to $2.47M, but increased the initial screening group to 52,778 participants, of whom 3,801 would be screened by MRI). A high retinal-clinical score cutoff reduced costs to $2.9M while only requiring 13,572 screened participants (of these only 3,801 would require MRI).

Conclusion:
A 2-stage recruitment design with a low-cost pre-screening retinal and clinical measure is a promising approach, resulting in a reduction of theoretical recruitment costs for recruiting persons with significant WMH burden compared to an MRI-only design.