bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP179: Clinical Outcomes in Acute Stroke in Patients Undergoing Emergency Intracranial Stenting Receiving IV Thrombolysis
Authors: Chaudhry Saqib A , Khan Hamza , McHugh Ashley , Chaudhry Mohammad Rauf A , Ali Akif , Fang Yun , Shah Zakriya , Fahadan Fahadan , Altaweel Laith , Qureshi Adnan
Published: February 2024

Background:
Stent-retriever thrombectomy is the first-line therapy for acute stroke with intracranial large vessel occlusion. In cases of stent-retriever thrombectomy failure, rescue stent angioplasty might be the sole option for achieving permanent recanalization. This study aims to evaluate the safety of combined intracranial vessel stent placement and thrombolysis.

Methods:
We conducted a retrospective analysis of patients with large vessel occlusion who underwent rescue stent angioplasty after stent-retriever thrombectomy between 2012 and 2023 in 8 neurovascular centers. We defined two binary outcomes: (1) functional clinical outcome (modified Rankin Scale 0-2) and (2) early symptomatic intracerebral hemorrhage (sICH). Clinical outcomes were assessed using uni- and multivariable logistic regression models.

Results:
A total of 216 patients were included, with target vessels located within the anterior circulation (133; 63.4%) and posterior circulation (79; 36.6%). Among patients who underwent emergency intracranial stenting, 66 (30.6%) received intravenous thrombolytic treatment. In multivariate logistic regression analysis, adjusted for age, gender, baseline NIHSS, target vessel, time to recanalization, number of passes including, and type of antiplatelet therapy, intravenous thrombolytic therapy was not associated with symptomatic ICH (odds ratio (OR) 1.05, 95% confidence interval (CI) 0.27-4.14, p=0.9502), but it was associated with a functional clinical outcome at 90 days (OR 3.39, 95% CI 1.11-10.43, p=0.0325).

Conclusions:
The use of rescue stent angioplasty can be considered after unsuccessful stent-retriever thrombectomy, along with intravenous thrombolytic therapy. Patients receiving intravenous thrombolytic therapy before the procedure exhibited higher rates of good functional outcomes.
Abstract WP183: Intracranial Atherosclerotic Disease in Acute Basilar Artery Occlusion
Authors: Mierzwa Adam T , Al Kasab Sami , Nelson Ashley , Ortega Santiago , Vivanco-Suarez Juan , Farooqui Mudassir , Jadhav Ashutosh P , Desai Shashvat , Toth Gabor , Alrohimi Anas , Nguyen Thanh , Klein Piers , AbdalKader Mohamad , Pandey Aditya , Koduri Sravanthi , Vora Shivangi , Aladamat Nameer , Gharaibeh Khaled , Afreen Ehad , Zaidi Syed , Jumaa Mouhammad A
Published: February 2024

Background:
Intracranial Atherosclerotic Disease (ICAD) large vessel occlusion (LVO) is responsible for up to 30% of anterior circulation LVOs and is less amenable to mechanical thrombectomy. In this study we aim to determine the prevalence of ICAD acute basilar occlusion and the likelihood of favorable functional outcomes (mRS 0-3) compared to embolic basilar occlusion.

Methods:
This is an analysis of PC-SEARCH Thrombectomy Registry in which consecutive patients with acute basilar artery occlusions from 8 high-volume comprehensive stroke centers were included from January 2015 to December 2021. Patients were dichotomized into two cohorts: with or without underlying ICAD. Descriptive statistics for each group and multivariate logistic analysis was performed on the primary outcome.

Results:
Three-hundred-ninety-nine patients were included in this analysis. There were 143 (36%) and 256 (64%) patients with and without ICAD; respectively. Baseline demographics were equivalent between the two groups except for gender (male 67% vs 47%; p < 0.001), history of stroke (24% vs 14%; p = 0.01), and atrial fibrillation (18% vs 30%; p = 0.01). Presenting NIHSS was similar between groups (15 vs 16; p = 0.85), however, pc-ASPECTS was higher in the ICAD group (9 vs 8; p = 0.02). At 90 days, patients with ICAD were less likely to achieve favorable functional outcomes (OR 0.33 95% CI 0.18 - 0.59; p < 0.001) after adjusting for potential confounding factors. Additionally, ICAD patients were less likely to achieve TICI ≥2b (38% vs 49%; p < 0.001). There were equivalent rates of symptomatic ICH between groups (OR 0.8 95% CI 0.29 - 2.22; p = 0.66).

Conclusion:
Acute basilar artery occlusions with underlying ICAD have higher likelihood of morbidity and mortality. Lower rates of successful recanalization in the ICAD cohort support this finding; however, rates of sICH were similar between the two cohorts.
Abstract WP188: Differences in Outcomes Due to Anesthesia Management During Endovascular Treatment of Patients With Acute Ischemic Stroke Due to Tandem Lesions
Authors: Galecio Castillo Milagros , Farooqui Mudassir , Hassan Ameer E , Divani Afshin A , Jumaa Mouhammad A , Ribo Marc , Petersen Nils H , Abraham Michael G , Malik Amer M , Johanna Fifi , Guerrero Waldo , Siegler James E , Nguyen Thanh , Sheth Sunil , Yoo Albert J , Linares Guillermo , Janjua Nazli A , Quispe-Orozco Darko , TEKLE WONDWOSSEN , Sabbagh Sara , Zaidi Syed F , Zevallos Cynthia , Abdalkader Mohamad , Rizzo Federica , Qureshi Abid , Majidi Shahram , Elgendy Omnea , Salazar-Marioni Sergio , Soomro Jazba , Gordon Weston , Rodriguez Aaron , Vivanco-Suarez Juan , Mokin Maxim , Yavagal Dileep R , Ortega-Gutierrez Santiago
Published: February 2024

Background:
Endovascular therapy (EVT) has been reported to be safe and effective for acute ischemic stroke (AIS) patients with tandem lesions (TLs). However, the optimal anesthetic management during EVT for TL patients is unknown. We aimed to assess the impact of anesthesia modality on clinical outcomes in AIS patients with TLs.

Methods:
Patient level data were pooled from 16 centers for anterior circulation TLs from 2015-2020. Patients were divided into general anesthesia (GA) and procedural sedation (PS). Multivariable logistic regression was used to assess the association of outcomes including modified Rankin Score (mRS) 0-2, ordinal shift is mRS, symptomatic intracranial hemorrhage (sICH), successful reperfusion (mTICI score ≥2b), excellent reperfusion (mTICI 3), first pass effect (FPE), early neurological recovery (ENI), door to skin puncture and reperfusion, and 90-day mortality.

Results:
Among 691 patients, 595 (GA:230 [38.7%] and PS:365 [61.3%]) were included in the final analysis. Patients treated with GA had lower odds of mRS 0-2 (36.6% vs. 52.5%, aOR: 0.56, 95% CI: 0.38-0.84,
p
=0.005) and favorable shift in 90 days mRS (aOR: 0.71, 95% CI: 0.51-0.99,
p
=0.041) when compared to PS. No differences were noted for sICH (3.9% vs. 4.7%, aOR: 0.66, 95% CI: 0.26-1.66,
p
=0.38), successful reperfusion (89.1% vs 86.5%, aOR: 1.59, CI: 0.87-2.89, p=0.13), excellent reperfusion (48.5% vs 50.3%, aOR: 0.85, CI: 0.56-1.30, p=0.462), FPE (53.6% vs 63.4%, aOR: 0.67, CI 0.45-1.0, p=0.05), ENI (38.9% vs 38.8%, aOR: 0.70, CI: 0.44-1.12, p=0.138), mortality at 90 days (20.3% vs 16.3%, aOR: 0.74, CI: 0.29-1.87, p=0.525), door to skin puncture (80 [46-117.5] mins vs 54 [21-100], p=0.607) and skin puncture to reperfusion (59 [39.5-85.5] mins vs 54 [38-81], p=0.836).

Conclusions:
In patients with AIS with TLs treated with EVT, GA was associated with lower odds of functional independence without a significant increased risk of sICH, mortality, or treatment delays.
Abstract WP19: Is Direct Oral Anticoagulant More Effective Than Warfarin to Reduce Size of Left Atrial Thrombus in Stroke Patients?
Authors: Nishimura Takuya , Aoki Junya , Terakado Mariko , Suzuki Fumiaki , Sakamoto Yuki , Terasawa Yuka , Sakai Kenichiro , Iguchi Yasuyuki , Anan Yuhei , Fujimoto Shigeru , Yoshimura Sohei , Ihara Masafumi , Koga Masatoshi , Kimura Kazumi
Published: February 2024

Objective:
The presence of left atrial thrombus (LAT) in acute stroke patients with nonvalvular atrial fibrillation (NVAF) is the major embolic source for recurrent stroke. The aim of this study was to investigate whether direct oral anticoagulants (DOAC) is more effective than warfarin to reduce the size of LAT detected in acute stroke patients with NVAF.

Methods:
Among acute stroke patients admitted to five major comprehensive stroke centers from January 2017 to December 2022, acute stroke patients with both AF and LAT detected by transesophageal echocardiography (TEE) were selected, and patients with follow-up evaluation were enrolled. All patients were treated with anticoagulation such as DOAC or warfarin for LAT. Thus, patients were classified into two groups according to the type of anticoagulation; the DOAC group and the warfarin group. We compared the clinical characteristics, the dissolution of LAT, and recurrent stroke within three months after stroke onset evaluated between the two groups.

Results:
63 patients (median age 77, male 33 [52%]) were enrolled. DOAC and warfarin groups had 22 (35%) and 41(65%) patients, respectively. Age, gender, NIHSS scores on admission were not different between the two groups. Age was 77 years (IQR, 68-81) in the DOAC group and 76 years (IQR, 68-81) in the warfarin group (P=0.644). 10 men (46%) were in the DOAC group, and 23 (56%) were in the warfarin group (P=0.442). The NIHSS score at admission was 3 (IQR, 1-18) in the DOAC group and 4 (IQR, 2-14) in the warfarin group (P=0.393). Initial LAT size was 0.83 (IQR, 0.41-1.27) cm2 in DOAC and 0.88 (IQR, 0.40-1.56) cm2 in warfarin (p=0.48). On follow-up evaluation (10 [IQR, 7-15] days after initial TEE), the disappearance of LAT was more frequently seen in DOAC group than warfarin group (13/22 [59%] vs. 14/41 [34%], P=0.016). Recurrent stroke within three months after stroke was 1/22 (5%) in DOAC and 3/41 (7%) in warfarin (P=1.000), which was not different.

Conclusion:
In acute stroke patients with NVAF, DOAC should be more effective than warfarin to dissolve LAT detected by TEE.
Abstract WP194: Quantified Effects of Intra-Arterial Vasodilatory Therapy for Cerebral Vasospasm
Authors: Anderson Matthew N , Sen Rajeev D , Prijoles Keiko Lynne , Cha Nathaniel , Raub Spencer , Winter Ashtyn , Galang Christine , Levitt Michael , Ghodke Basavaraj V , Walker Melanie
Published: February 2024

Introduction:
Cerebral vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Though used routinely in clinical practice, objective metrics to evaluate effectiveness of intra-arterial vasodilatory treatment (IAT) have not been identified. To quantify effects of IAT on flow dynamics in cerebral vasospasm, we retrospectively compared Lindegaard ratios (LR) of aSAH patients pre-and post-IAT.

Methods:
Subjects included 24 aSAH patients undergoing IAT in the bilateral middle cerebral arteries (MCA) for cerebral vasospasm, diagnosed by standard clinical and radiographic criteria. Subjects were excluded if balloon angioplasty was performed prior to/within 2 days of the index procedure. All subjects received 10 mg IA milrinone, a non-catecholamine phosphodiesterase inhibitor drug, per MCA. Transcranial doppler (TCD) ultrasound was measured pre-IAT (D0) and at D+1 and D+2 post-IAT. LR was calculated as the ratio of mean flow velocities in the middle cerebral artery (MCA) to the ipsilateral extracranial internal carotid artery. Standard threshold for vasospasm is defined as LR>3.

Results:
Right and left LR were aggregated, total N=48. Average pre-IAT LR was 2.96 (R 2.67/L 3.25±1.29). Post-IA LR were 2.72±1.12 and 3.15±1.55 at D+1 and D+2, respectively. Subjects with pre-IA LR>3 showed an average LR decrease of 21% post-IAT D+1 (p=0.01) and an 8% decrease at D+2 (p=0.16) [Fig.1A]. Subjects with pre-IAT<3 experienced an average LR increase of 28% by D+2 (p=0.02) [Fig 1B].

Conclusion:
Subjects with TCD confirmed vasospasm (LR>3) at D0 showed a significant improvement in cerebral blood flow one day after therapy. Subjects who did not meet TCD threshold for vasospasm (LR<3) showed little change one day post-IAT but worsening cerebral blood flow by day two post-IAT. Further study is needed to determine whether LR can be used to predict benefit or objectively assess effectiveness of IAT in aSAH patients with cerebral vasospasm.
Abstract WP208: Infarction Size Affects Clinical Outcomes in Emergent Carotid Artery Stenting With Mechanical Thrombectomy
Authors: Mahmoud Noor A , Almeida Nyle C , Singh Raman , Xu Chao , Chen Sixia , Shakir Hakeem J , Sidorov Evgeny V
Published: February 2024

Background:
Management of large vessel occlusion with extensive ipsilateral internal carotid artery (ICA) occlusion is unknown. We evaluated patients who underwent emergent carotid artery stenting (CAS) of the ICA with mechanical thrombectomy (MT).

Methods:
We retrospectively collected baseline demographic, clinical, and radiographic data on 27 patients who presented as a stroke alert within 24 hours of symptoms and had extensive (from bifurcation to distal ICA) occlusion by computerized tomography angiography from 2019-2023 at our institution. All patients underwent CAS with MT and received dual antiplatelet therapy. We measured outcomes by: (1) development of symptomatic ICH at 24 hours, (2) mortality, (3) Modified Rankin Scale (mRS) at 90 days, and (4) change in NIHSS at 24 hours. Baseline characteristics were reported by descriptive statistics. Statistical analyses were completed using Fisher’s exact test, Wilcoxon rank sum test, and logistic regression. Differences were statistically significant at
p
< 0.05.

Results:
The mean age for our cohort was 64.5 ± 10.62 and nine patients were females (33.3%). Sixteen had M1 (59.3%) while 10 had M2 occlusion (37%), 14 patients received IV tPA (51.9%), and mean NIHSS at presentation was 15.6 ± 5.99. All patients achieved TICI 2b or TICI 3 recanalization. In our cohort, patients with lower ASPECT score 7.4 ± 1.8 compared to those with higher ASPECT score 9.0 ± 1.0 were more likely to have symptomatic ICH (
p
= 0.032), and higher odds of mortality OR = 0.496, 95% CI (0.261-0.945). The development of symptomatic ICH at 24 hours following procedure was associated with severe disability (mRS 4-6) at 90 days (
p
= 0.032). Administration of intravenous tPA was significantly associated with improvement of 4 or more points on NIHSS at 24 hours (
p
= 0.032), but not with symptomatic ICH (
p
= 0.419). Age, NIHSS at presentation, systolic blood pressure, and diabetes mellitus were not associated with mortality or symptomatic ICH.

Conclusion:
The area of infarction at the time of presentation (ASPECT score) is an essential factor in stratifying patient selection for emergent CAS during MT in extensive internal carotid artery occlusion. Further studies are needed to evaluate infarction size for safe interventions.
Abstract WP214: Embolization in Chronic Subdural Hematomas
Authors: Gupta Rishi , Yadav Ellora , Humphries William E , Khaldi Ahmad
Published: February 2024

Introduction:
Middle meningeal artery embolization for chronic subdural hematomas is a promising treatment either as an adjuvant to surgical evacuation of the hematoma or as a primary treatment modality. Current randomized trials are ongoing, but there is a lack of clarity as to which embolic agent may be more effective in preventing hematoma expansion. The current study examines if there is a difference between particle and liquid embolic agents for this indication.

Methods:
This is a single center retrospective study from May 2019- May 2023 where 160 consecutive patients with chronic subdural hematomas were treated with embolization. In August 2021, operators at our institution switched from using NCBA or Onyx to Embospheres. We analyzed if there were differences in complication rates, requirement for surgery after embolization and changes in 90 day CT imaging with regards to resolution. A Fisher’s exact chi square test was used for binary variables and student’s t-test for continuous variables.

Results:
A total of 160 patients were treated with embolization and the mean age was 71± 11 years with 45 (28%) presenting with bilateral subdural hematomas. The mean maximal diameter of the collection was 16.3 ± 6.6 mm and midline shift of 4.8±4.4 mm. A total of 67 patients (42%) were treated with particles and 93(58%) with liquid embolic agents. There was one patient with facial nerve palsy in the liquid embolic group and one patient with transient vision symptoms and three with post procedural seizures in the particle embolization group. More patients treated with liquid embolic agents were on anti-platelets or anti-coagulants compared to the particle group (34% vs. 16%, p<0.01). There was no difference in requirement of surgery between the two groups (3.2% vs. 1.4%, p<0.49). Both groups had similar reduction of the maximal diameter with no difference noted at 90 days (3.9 vs. 4.4 mm, p<0.59).

Conclusions:
The current analysis provides preliminary evidence of the safety of both agents and no difference in outcomes noted between the two groups. A well designed future randomized trial would be helpful given the cost differences between the two types of agents.
Abstract WP219: Diffusion Weighted Imaging Characteristics in Deep White and Gray Matter Structures in Pediatric Patients With Moyamoya Disease
Authors: Domi Trish , Mohamed Ahmed , Kasa Loxlan , Abdullah Alhusain , Robertson Amanda , Pulcine Elizabeth , Moharir Mahendranath , Dirks Peter , Krishnan Pradeep , Muthusami Prakash , Dlamini Nomazulu
Published: February 2024

Background:
Moyamoya Disease (MMD) is a steno-occlusive arteriopathy associated with transient ischemic attacks, stroke, and cognitive impairments. In adult MMD, normal-appearing deep gray and white matter structures (NADWM) show diffusion changes that are associated with cognitive impairments. Apparent diffusion coefficient [ADC] measures the mean diffusion and is sensitive to these changes. The association of ADC changes in NADWM in pediatric MMD is not clear. Our objective is to determine whether ADC is elevated in NADWM in pediatric MMD patients.

Hypothesis:
ADC values in NADWM will be elevated in MMD patients compared to controls.

Methods:
Twenty-nine MMD patients and no stroke and 7 healthy controls (HC) were included in a single center, retrospective study. Diffusion and T1-weighted images were analyzed. We constructed a script implementing a convolutional neural network (CNN) based approach to segment and binarize cortical regions of interest (ROI) and allow extraction of ADC values (units =[x10
-6
mm
2
/s]). Segmented ROIs included: 1) all white matter (WM), and NADWM including: 2) thalamus, 3) caudate, 4) putamen, 5) globus pallidus, 6) hippocampus. Mean ADC values were compared for: 1) all ROIs between MMD and controls, and 2) all ROIs in the MMD affected and the contralateral hemispheres within the MMD group.

Results:
Patients were on average 7.7
+
5.4 years at MMD diagnosis. In all WM, MMD patients had significantly higher ADC values than controls in the left (mean= 865.7
+
101.6 versus 762.4
+
21.6, p=0.01) and right hemispheres (mean= 869.9
+
104.9 versus 761.0
+
21.3, p=.01), respectively. In NADGM, there were no significant differences found between the MMD and control groups in any of the NADGM ROIs. In the NADGM of MMD patients, higher ADC values were found in the putamen (mean= 778.2
+
46.0, p=0.041), hippocampus (mean=1009.5
+
58.6, p=0.005) and all NAWM (mean= 860.3
+
57.0, p<0.0001) in the MMD affected compared to the contra-lesional hemisphere.

Conclusions:
In pediatric patients with MMD, we found elevated ADC values in deep gray and white matter structures in the diseased hemisphere indicating alterations in the underlying microstructure. Our future analysis will integrate hemodynamic profiles and cognitive outcomes.
Abstract WP224: Association of Quality-of-Life Domains and Clinical Symptoms in Pediatric Cerebral Cavernous Malformation Patients
Authors: Chawla Shweta , Ortiz Ambrosio Mateo , Huynh Nhu , Nelson Jeffrey , McCulloch Charles , Vassar Rachel , Smith Edward , Vadivelu Sudhakar , Akers Amy , Lee Cornelia , Zabramski Joseph M , Torbey Michel T , Morrison Leslie , Awad Issam A , Kim Helen
Published: February 2024

Introduction:
Cerebral cavernous malformations (CCMs) in children are associated with focal seizures, intracranial hemorrhage, and neurologic deficits, impacting quality of life (QoL). However, previous studies have not evaluated the impact of CCMs on QoL domains in pediatric populations.

Methods:
Completed self-reports (n=16) or parent-proxy reports (n=32) measuring patient outcomes in physical, mental and social health domains were collected from 48 pediatric familial CCM patients (5-17 years) enrolled in the Brain Vascular Malformation Consortium (BVMC) CCM study between 2019-2022. Survey responses were converted into domain T-scores and standardized against a reference population (mean (
M
)=50, SD=10). Scores were oriented for higher scores to reflect worse outcomes. One-sample t-tests analyzed whether mean T scores for each domain differed significantly from 50 (p<0.05). Multivariable linear regression tested whether PROMIS domain T scores were associated with (a) prior hemorrhage, (b) history of seizures, and (c) history of headaches, adjusting for age and sex. Standardized effect sizes were reported.

Results:
Compared to the reference population, pediatric CCM patients reported significantly better levels of mobility (
M=
-2.47, 95% CI=-4.25 to -0.08; p=0.042), anxiety (
M
=-4.66, 95% CI=-8.37 to -0.04, p=0.02), depression (
M=
-6.13, 95% CI=-8.79 to -3.47, p<0.01), fatigue (
M
= -7.40, 95% CI=-10.64 to -4.16, p<0.01), and pain
(M
=-6.71, 95% CI=-9.79 to -3.63, p<0.01). Multivariable linear regression showed that CCM patients with a history of headaches had impacted peer relationships compared to those without headaches, with an effect size of 7.86 (95% CI=0.162 to 15.55, p=0.05). Patients with a history of seizures reported higher pain scores compared to those without seizures, with an effect size of 5.58 (95% CI=-0.603 to 11.77, p=0.08).

Conclusion:
Psychological and social functioning domains, particularly experiences in pain and relationships, were impacted in the pediatric CCM population. Further studies conducted with larger sample sizes could determine if the PROMIS questionnaire can reliably assess patient or proxy-reported outcomes in the pediatric CCM population and evaluate within-person changes over time.
Abstract WP236: Harmonization of Stroke Risk Prediction Variables Using Natural Language Processing
Authors: Mallya Pratheek , Zhao Juan , Hong Chuan , Henao Ricardo , Wojdyla Daniel , Schibler Tony , Manchanda Vihaan , Pencina Michael , Hall Jennifer L
Published: February 2024

Introduction:
Early identification of stroke risk can profoundly influence an individual's chance of survival. While machine learning-based stroke risk prediction models perform better than traditional counterparts, they require integrating diverse open data sources. Variable discrepancies - where the same concept is described differently - pose challenges for data integration, requiring time-intensive manual harmonization. To address this, we developed an automated harmonization technique using natural language models.

Methods:
We utilized data from the Atherosclerosis Risk in Communities (ARIC), Multi-Ethnic Study of Atherosclerosis (MESA), Framingham Offspring Study, and Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohorts. Our approach involved training a two-layer fully connected neural network (FCN) to predict a harmonized ‘concept variable’ based on variable descriptions. These predictions employed embeddings from Bidirectional Encoder Representations from Transformers for Biomedical Text Mining (BioBERT). Further refining was achieved through paired sentence classification tasks to determine if description pairs shared identical concepts. We experimented with both separate cohort training and combined cohort training to evaluate context dependency. We used cosine similarity between the embeddings of the pre-trained BioBERT encoder as a prediction score for our baseline method.

Results:
The harmonization methods using natural language models outperformed the baseline method. The FCN model improved the area under the receiver operating characteristic from 0.787 (baseline) to 0.985 for the paired classification task. For harmonization concept prediction, the top-2 accuracy - correct prediction in the top two answers - improved from 11.9% (baseline) to 54.6%, while the top-5 accuracy improved from 16.1% (baseline) to 67.6%.

Conclusions:
Utilizing natural language processing for data harmonization provides a scalable approach that improves accuracy and efficiency of prediction. This facilitates the inclusion of diverse cohorts, broadening the sample size and range of indicators available, which in turn advances the versatility and the generalizability of stroke risk prediction models.
Abstract WP237: Anticoagulant Utilization and Risk of Thromboembolic Events Following Ischemic Stroke Among Adults With Cancer
Authors: Acton Emily K , Navi Babak B , Kasner Scott E
Published: February 2024

Rationale:
Ischemic stroke and cancer frequently coexist, but there are limited data from population-based cohorts regarding prevalence, risk of subsequent thromboembolic events, and treatments.

Methods:
We leveraged large-scale healthcare data to assess recurrent thromboembolic events in the 6 months following discharge for ischemic stroke among a nationally representative U.S. population with active cancer. Landmark analyses were undertaken with anticoagulant exposure status based on dispensations in the week following hospital discharge. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard models with robust variance estimators to account for clustering within propensity score-matched pairs.

Results:
Among 86,365 adults discharged after an ischemic stroke between 10/2020-09/2021, 10.2% had active cancer. Based on eligibility criteria (including removal of those with known atrial fibrillation), 4,819 were assessed [median age 74 years; 48.7% female; common cancer types: 25.3% gastrointestinal, 20.3% prostate, 18.4% lung]. Anticoagulants were dispensed to 14.7% of the cohort in the week following discharge. Incidence of thromboembolic event recurrence was 37.5 per 100 person-years (66.7% ischemic stroke). Initial anticoagulation was associated with an increased risk of thromboembolism recurrence (aHR=1.42, 95% CI: 1.06-1.90).

Conclusions:
This large-scale real-world study demonstrates an estimated 10% of patients with ischemic stroke had active cancer, and they faced a very high 6-month incidence of recurrent thromboembolism. Anticoagulants were not commonly prescribed after discharge, suggesting that clinicians use them less commonly for stroke than for venous thromboembolism in cancer patients. The higher risk of recurrent events on anticoagulants likely reflects residual confounding by indication. Clinical trials are needed to further assess optimal antithrombotic strategies in this population.
Abstract WP260: Higher Incidence of Cerebral Venous Thrombosis Seen During the First Year of the COVID-19 Pandemic: Insights From the National Inpatient Sample
Authors: Christopher Kara M , Alshekhlee Zina , Overberg Rachel , Naidu Aniketh , Edgell Randall C
Published: February 2024

Background:
Cerebral venous thrombosis (CVT) is associated with significant risk of death and disability. Prior research has found patients with COVID-19 had higher incidences of system venous and arterial thrombosis, however, there has been little research into its impact on incidence of CVT.

Objective:
Determine whether the incidence of CVT was higher during the first year of the COVID-19 pandemic.

Methods:
A cross-sectional study utilizing data from the National Inpatient Sample (NIS) was performed. Adult patients in 2018 (n=6,051,974) were compared to those in 2020 (n=5,470,813), the first year of the COVID-19 pandemic. To prevent potential confounding by undiagnosed COVID-19, patients in 2019 were not utilized in the analysis. ICD-10 codes were utilized to identify patients with CVT along with additional diagnoses, including COVID-19 infection. Odds ratios and 95% confidence intervals were calculated and compared using t-tests. Rates of CVT were also calculated.

Results:
There were 731 (weighted estimate for the US population n=3,655, rate of 13.4 cases per 100,000 admissions) patients with CVT in 2020, compared to 641 patients in 2018 (weighted n=3,205, rate of 10.6 per 100,000 admissions; p-value 0.003; cOR=1.26, 95% CI=1.08-1.47). Female patients had a higher incidence of CVT in both years (58.6% versus 62.5%) with no significant between year difference. No age or race difference was identified. Hospital mortality rate among CVT patients admitted in 2020 was 5%. Twelve patients were diagnosed with concurrent COVID-19 infections. Length of stay among CVT patients admitted in 2018 and 2020 was similar (7.89 versus 8.06 days). However, CVT patients with concurrent COVID-19 had a longer hospital stay than those without COVID-19 (18 versus 8 days; p-value<0.001).

Conclusions:
There was a significantly higher incidence of CVT among hospitalized patients during the first year of the COVID-19 pandemic compared to 2018. This finding is consistent with the previously described higher rates of thrombotic disorders during the COVID-19 pandemic and should prompt further study.
Abstract WP265: Connecting the Dots: Human Development Index and Stroke Burden in ASEAN
Authors: Darumurti Rissito C , Widyasari Vita , Taufiqurrohman Agus
Published: February 2024

Introduction:
Stroke's far-reaching impact encompasses societal, economic, and healthcare dimensions. A country's Human Development Index (HDI), comprising its performance in health, education, and living standards, offers insights into the nation's capacity in stroke management. The Association of Southeast Asian Nations' (ASEAN) adaptive growth strategy, accommodating the diverse developmental stages of its members, presents a unique context for exploring the relationship between HDI and stroke burden in the region.

Methods:
Data regarding the burden of stroke, expressed in the form of stroke-related mortality and Disability-Adjusted Life Years (DALY) rates, within the current 10 members of ASEAN were sourced from the 2019 Global Burden of Disease (GBD) study. Data on the 2019 HDI for these countries were obtained using the tool on the United Nations Development Programme (UNDP) website. Statistical analysis included normality testing and correlation assessments using Pearson and Spearman methods across 3 age groups (all-ages, 20+, 55+) with 3 sex sub-groups (both-sexes, female, male) in each age category.

Results:
In terms of mortality, higher HDI correlated significantly with lower mortality rates in all three age groups for both-sexes and female sub-groups. The male sub-groups also showed similar findings in the 20+ and 55+ age groups, but no significant correlation was found in the all-ages group (Table 1). For DALY, a significant correlation was observed between higher HDI and reduced DALY rates in the 20+ and 55+ age groups across all sex sub-group, but no significant correlation emerged in the all-ages group for any of its sex sub-groups (Table 2).

Conclusion:
These findings collectively suggest that higher levels of human development, as indicated by HDI, are associated with lower stroke-related mortality and DALY rates in ASEAN countries, emphasizing the importance of effective strategies to alleviate the burden of stroke in the region.
Abstract WP27: Tissue Kallikrein Attenuates Ischemic Edema by Increasing Water Transport Function of AQP4 in Glymphatic System in pMCAO Mice
Authors: zhang Jianying , Cao Wenjie , Dong Qiang
Published: February 2024

Aquaporin-4 (AQP4) is an essential water channel protein in GS (glymphatic system), and is widely distributed in astrocytes at the brain/cerebrospinal fluid interface, where it facilitates water movement. Altered AQP4 polarization and expression are evident in cytotoxic edema in pMCAO mice in our previous study, glymphatic MRI of which also shows reduced CSF tracer entry and clearance. Tissue Kallikrein treatment provides cerebral infarction patients with vasodilatory activity, which may facilitate the dynamics of CSF in GS. We hypothesized that TK could attenuate depolarization of AQP4 to confer benefit in brain edema by boosting the kinetics in GS. In this study, we evaluated the effects of TK on mice acute ischemic edema in both wild and AQP4-/- pMCAO models. A fluorescent tracer was injected into the striatum of both mice, and the infusion pattern of the fluorescent tracer in the brain parenchyma was detected to confirm the function of AQP4 in alleviating edema by TK. Concurrently, immunohistochemistry analysis was performed to explore the altered AQP4 polarization and expression in TK treatment animals. Our results indicated that TK attenuated brain edema was associated with improved transport function of AQP4 to CSF in pMCAO mice, which might relate to the alteration of polarization and expression of AQP4.
Abstract WP280: Health and Functional Ability of Veterans and Non-Veterans With Stroke: An Analysis of the 2021 Behavioral Risk Factor Surveillance System
Authors: Lyerly Michael J , Williams Linda
Published: February 2024

Introduction:
Veterans represent a unique population who may be at higher risk of developing stroke. The association between Veteran status and stroke and associated outcomes have not been well described.

Methods:
We performed a retrospective, cross-sectional analysis of the 2021 Behavioral Risk Factor Surveillance System. Participants were stratified based on Veteran status. Demographics, social factors, and vascular risk factors were compared between the two groups. Logistical regression models were created to explore the association between Veteran status and stroke. Health and functional limitations were also compared between Veterans and Non-Veterans with stroke.

Results:
We identified 52,518 Veterans and 382,958 Non-Veterans. Veterans more often self-reported a history of stroke compared to non-veterans (6.2% vs. 3.6%, p<0.001). Veterans more often reported a history of diabetes, tobacco use, and obesity. After adjusting for demographic, social and vascular factors, Veterans remained at a higher odds of having a history of stroke (OR 1.26 [95% CI 1.20-1.33], 1.22 weighted, Table). Veterans and Non-Veterans with a history of stroke report similar self-reported measures of health and functional status although Veterans may have more difficulty with ambulation.

Conclusions:
Using a sample not limited to the Veterans Health Administration, we observed higher rates of self-reported stroke among Veterans compared to Non-Veterans which is not fully explained by differences in their demographics, social factors, or vascular health history. Despite this, Veterans with stroke appear to have similar overall health and functional abilities compared to non-Veterans.
Abstract WP283: Association of High-Risk Cardioembolic Sources on Cardiac CT With Acute Ischemic Stroke: A Case-Control Study
Authors: Nio Shan Sui , Rinkel Leon A , van Schuppen Joost , Spijkerboer Anje M , Beemsterboer Chiel , Guglielmi Valeria , Bouma Berto , Boekholdt S , Lobe Nick H , Beenen Ludo , Marquering Henk , Majoie Charles B , Roos Yvo , van Randen Adrienne , Planken R. Nils , Coutinho Jonathan M
Published: February 2024

Background:
Cardiac CT is increasingly used to detect a source of cardioembolism in stroke patients. We assessed the association between sources of embolism on cardiac CT, which were predefined as high-risk, and acute ischemic stroke.

Methods:
We analyzed data from Mind the Heart, a prospective, single-center, observational cohort study, and included consecutive patients with a suspected stroke who underwent ECG-gated cardiac CT during the initial stroke imaging protocol. Cases were patients with a final diagnosis of acute ischemic stroke (AIS), established by an adjudication committee. Controls were patients with stroke mimics (SMi). We excluded patients with a transient ischemic attack. Cardiovascular radiologists diagnosed structural high-risk sources of cardioembolism on cardiac CT according to predefined criteria. High-risk sources on cardiac CT were: cardiac thrombi, signs of endocarditis, recent myocardial infarction, prosthetic valve abnormalities, atrial myxomata and signs of rheumatic valvular disease. We used logistic regression, adjusting for age, sex, history of atrial fibrillation, and history of myocardial infarction.

Results:
Of 607 included patients, 452 had AIS (74%, median age 72, 59% male) and 155 had a SMi (26%, median age 70, 46% male). Diagnoses in the SMi group were: seizures (45/155, 29%) peripheral vestibulopathy (22/155, 14%), functional neurologic symptoms (16/155, 10%), benign headache disorder (8/155, 5%), intoxication (7/155, 5%), and other diagnoses (57/155, 37%). Cardiac CT detected a structural high-risk cardioembolic source in 52/452 AIS patients (12%) and in 5/155 SMi patients (3%, three patients with seizures, one with peripheral vestibulopathy and one with traumatic brain injury, aOR: 4.1, 95%CI 1.7-12.1). Cardiac thrombi were the most commonly observed high-risk sources of embolism and were detected in 38 (8%) AIS patients and in 2 (1%) SMi patients (aOR 7.0, 95%CI 2.1-43.9).

Discussion and conclusion:
A high-risk source of cardioembolism was detected on cardiac CT four times more often in patients with acute ischemic stroke than in patients with a stroke mimic. These data substantiate the clinical relevance of using acute CT to search for sources of cardioembolism in ischemic stroke patients.
Abstract WP289: Insufficient Low-Frequency Blood Pressure Activity Under Orthostatic Stress Predicts Blunted Night-to-Day Blood Pressure Dipping in Patients With Ischemic Cerebrovascular Disease
Authors: Ma Xin , Kong Qi , Chen Hongxiu , Xing Yingqi
Published: February 2024

Introduction:
Blunted night-to-day blood pressure (BP) dipping was common in ischemic cerebrovascular disease (ICVD). BP dipping could be influenced by baroreflex, which stabilized BP by regulating sympathovagal balance. We sought to determine the relationship between baroreflex function and BP dipping in patients with ICVD.

Methods:
Patients with ICVD stable for at least 3 days were enrolled. Beat-to-beat BP and ECG were monitored in 3 phases of active standing [supine (S), supine to upright (SU), upright (U), 4 min each]. Baroreflex function was evaluated by time-domain and frequency-domain baroreflex sensitivity (BRS) and by indices of sympathovagal balance [low (0.04-0.15 Hz) to high (0.15-0.4 Hz) frequency ratio (LHR) of systolic BP (SBP) and RR interval (RRI)]. BP dipping was measured as percentage with 24h ambulatory BP monitoring. SBP dipping <0 was defined as reverse BP dipping.

Results:
Among 66 patients, mean SBP dipping was 3.54% ± 6.85%. SBP dipping was positively related to BP-LHR
SU
(Spearman r=0.258, p=0.036), but had no significant correlation with time-domain and frequency-domain BRS, LHR
S
and LHR
U
of BP and RRI, or RRI-LHR
SU
(Table 1). Lower log BP-LHR
SU
was indicative of less SBP dipping [β (95% CI): 6.53 (1.67-11.40), p=0.009] and the presence of reverse BP dipping [OR (95% CI): 0.11 (0.02-0.65), p=0.015], even after adjusting age, sex, vascular risk factors, 24h mean BP level, NIHSS and mRS scores (Table 2).

Conclusions:
Low BP-LHR
SU
, which suggested sympathetic underactivation of BP activity during the orthostasis-stimulated baroreflex engagement, might be a pathophysiological link between baroreflex impairment and blunted BP dipping in ICVD.
Abstract WP296: Human Vascular Smooth Muscle Cells Derived Small Extracellular Vesicles Reduce the Neurovascular Damage After Stroke in Diabetic Mice
Authors: Cui Xu , Chopp Michael , Zacharek Alex , Zhang Zheng Gang , Liu Xianshuang
Published: February 2024

Introduction:
Stroke patients with type-2 diabetes exhibit exacerbated cerebrovascular dysfunction and increased neurological deficits compared to non-diabetic stroke patients. Vascular smooth muscle cells (VSMCs) play an important role in mediating neurovascular function, however, how VSMCs communicate with cerebral endothelial cells (CECs) has not been studied. In this study, we tested the hypothesis that small extracellular vesicles (sEVs) derived from healthy human VSMCs (VSMC-sEVs) reduce diabetes- and ischemia-neurovascular damage.

Methods and Results:
VSMC-sEVs were characterized. In vitro CEC permeability assay showed that treatment of hypoxia-challenged human brain microvascular endothelial cells (BMECs) or primary CECs isolated from type-2 diabetic mice (n=6/group) with VSMC-sEVs significantly reduced and augmented cell permeability and trans-endothelial electrical resistance, respectively, compared to non VSMC-sEVs control. Inhibition of sEV endocytosis in BMECs with clathrin (CPZ) or caveolin (Nystatin) inhibitors abrogated the effect of VSMC-sEVs on CEC proliferation and migration. We then examined the effect of VSMC-sEVs on diabetic ischemia in which diabetic mice, with diabetes induced by a high fat diet and streptozotocin, were subjected to permanent MCAo. Middle-age diabetic male mice (10-12m old) were treated with intranasal administration of VSMC-sEVs (1x10
9
particles per injection) or saline (n=12/group) at 24h after cerebral ischemia. We found that VSMC-sEVs treatment significantly increased regional cerebral blood flow and FITC-dextran perfused functional microvessels (17.55% vs 13.32% control) as well as decreased brain hemorrhage and BBB leakage (1.51% vs 1.76% of albumin, p<0.05) in the ischemic border zone 28 days after MCAo compared with the saline treatment mice. Moreover, compared to the saline treatment, VSMC-sEVs significantly improved neurological function after stroke as measured by modified neurological severity score, and foot-fault and adhesive removal tests, respectively.

Conclusion:
This study suggests that VSMC-sEVs have a therapeutic effect to improve neurological outcome after diabetic stroke, likely by reducing diabetes and ischemia impaired neurovascular function.
Abstract WP30: Therapeutic Hypothermia With Thin Liquid Convection is Safe and Feasible in Acute Stroke Patients: The Helping Stroke Patients With ThermoSuit Cooling (SISCO) Pilot Study
Authors: Salerian Justin A , Schock Robert B , Freedman Robert J , Schirmer Clemens , Sen Souvik , Goren Oded , Kupas Douglas F , Aysenne Aimee M
Published: February 2024

Introduction:
Animal studies have shown that therapeutic hypothermia of 32-34°C (TH) leads to a drop in infarct size after cerebral artery occlusion. Data suggests that early, rapid TH must be achieved to maximize neuroprotection from ischemic injury. There have been two RCTs of TH in stroke patients, both of which cooled slowly and failed to show the benefit of TH.

Objective:
The present study assessed the safety and feasibility of the ThermoSuit System (TSS) to induce rapid TH in acute ischemic stroke patients enrolled in the SISCO pivotal phase I trial. The TSS circulates cold water directly over the patient’s skin to achieve TH and has previously demonstrated significantly faster cooling than other methods.

Methods:
Eligible stroke patients were enrolled with an NIHSS > 5, less than 8 hours from LKW, or who met the extended window thrombectomy criteria. Patients were sedated and intubated according to protocols. Cooling was initiated by circulating ice-cold water (0-8°C) through the TSS. The patients were cooled until the core temperature reached 34-33°C, and the suit was removed. Temperature was maintained at 32°C to 34°C for 24 hours following the cooling induction using a conventional cooling blanket. Criteria for study success were defined as 1) at least 50% of the patients achieving 32-34°C within 1 hour; 2) NIHSS and mRS scores at 90 days post-stroke were not statistically worse than historical controls; 3) no significant increase in adverse event rates in cooled subjects vs. historical controls. RESULTS 14 subjects were enrolled, and 13 were cooled. 2 patients were excluded due to treatment delays and 1 due to missing outcome data, leaving 10 patients available for complete analysis. The average NIHSS on admission was 18, and the average patient age was 65. 7 patients had an LVO in the anterior circulation and 3 had posterior circulation strokes. All study success criteria were met. The median cooling time to 34°C was 40 minutes. The rates of unacceptable outcomes at 90 days (mRS >3) were 45% in 1314 published historical controls but only 10% in cooled subjects.

Conclusion:
The TSS is a safe and effective tool for rapid TH in ischemic stroke patients. Further studies are warranted to assess whether this cooling method is neuroprotective for these patients.
Abstract WP307: Combinatory Therapy With a PAF-Receptor Antagonist Plus a Lipid Mediator Provides Long-Lasting Protection in Experimental Stroke
Authors: Bazan Nicolas G , Reid Madigan M , Obenaus Andre , Mukherjee Pranab K , Khoutorova Larissa , Belayev Ludmila
Published: February 2024

Objective:
Neuroprotective efficacy observed during short survival periods may not necessarily apply to more extended survival periods, and some stroke-impaired behaviors recover naturally in rodent models 1-2 weeks after stroke. The objective of the present study was to test the hypothesis that acute LAU-0901 plus NPD1-induced neuroprotection endures in animals allowed to survive for several weeks after focal ischemic insult. Two small bioactive molecules were investigated: LAU-0901, a PAF-R antagonist that blocks pro-inflammatory signaling, and neuroprotectin D1 (NPD1), which activates cell-survival pathways, and their combination exerts potent anti-inflammatory activity in the brain.

Methods:
Male SD rats (290-360g) were subjected to 2h of middle cerebral artery occlusion (MCAo) by the intraluminal filament and treated with vehicle, LAU-0901 (60 mg/kg, IP), NPD1 (222 μg/kg, IV), LAU-0901+NPD1 at 3 h after onset of MCAo. Rats received neurobehavioral examinations during MCAo (60 min) and then on days 1, 2, 3, 7, and weekly during eight weeks survival period, followed by
ex vivo
MRI on weeks 4 and 8.

Results:
Physiological variables showed no significant differences among groups. No adverse behavioral side effects were observed after administering LAU-0901, NPD1, or LAU-0901+NPD1. LAU-0901 and NPD1 treatments alone significantly improved the behavior compared to the vehicle group on day 1 (by 32 and 33%), day 7 (38 and 40%), week 4 (38 and 39%), and persisting throughout eight weeks of survival period (by 58 and 44%, respectively). Combinatory treatment with LAU-0901+NPD1 dramatically improved behavior on days 1 (by 37), 2 (by 37%), 3 (by 36%), 7 (40%), and on weeks 4 (by 40%), 5 (44%), 6 (44%), 7 (44%) and 8 (41%) compared to vehicle group. Treatments with LAU-0901, NPD1, and NPD1+RvD1 reduced T2WI lesion volumes on week 4 by 32, 41, and 50% and tissue loss on week 8 by 83, 51, and 50%, respectively, compared to vehicles.

Conclusion:
These data suggest that LAU-0901 and NPD1 alone provide high-grade neuroprotection in the MCAo model. Combinatory therapy with LAU-0901 plus NPD1 is more effective than the single therapy affording synergistic neuroprotection with improved neurological recovery when administered at 3h after focal cerebral ischemia in rats.