bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP86: Systematic Review Of Aortic Atherosclerotic Plaque In Cryptogenic Stroke
Authors: Sakai Yu , Cao Quy , Pasyar Pouyan , Noel Peter B , Witsch Jens , Kasner Scott E , Cucchiara Brett L , Song Jae W
Published: February 2023

Introduction:
In patients with cryptogenic stroke (CS), complex aortic plaque may be a potential underlying etiology. We performed a systematic review to determine the prevalence of complex aortic plaque in CS patients.

Methods:
A systematic review and meta-analysis were performed according to PRISMA guidelines (PROSPERO: CRD42022300865). PubMed and EMBASE databases were searched from Jan 1980 to Nov 2021 for studies assessing aortic (ascending, arch, descending) plaque by transesophageal echocardiogram (TEE), CT/CTA, or MRI in at least 10 CS patients. Prevalence rates were pooled using a random-effects model. I
2
statistics assessed heterogeneity. An Egger’s test assessed publication bias.

Results:
From 2712 articles, 31 met inclusion criteria. Ascending, arch, and descending aorta were assessed in 65%, 100%, 55% of studies, respectively. Studies investigated aortic plaque by TEE (84%), CT/CTA (19%) and MRI (16%). The prevalence of complex aortic plaque in 4666 CS patients was heterogeneous across studies and yielded a summary prevalence of 30% (95% CI 23-38%, I
2
= 96%; Figure 1) contrasting with 11% (95% CI 5-20%, I
2
=83%) in 677 patients without stroke. Prevalence rates in women and men were 26% (95% CI 14%-43%, I
2
= 94%) and 35% (95% CI 21-52%, I
2
= 97%), respectively. To investigate geographic differences, 14 studies from Europe were pooled (32%, 95% CI 23-43%, I
2
=93%), 3 from the Middle East (34%, 95% CI 11-67%, I
2
=94%) and 3 from the US (28%, 95% CI 13-51%, I
2
=90%). No publication bias was detected (p=0.66). Sources of heterogeneity included patient selection, imaging technology (e.g, transducer frequency) and plaque measurement criteria.

Conclusions:
Studies suggest a prevalence rate of complex aortic plaque in approximately 30% of CS patients. However, significant heterogeneity in the results indicate a need for less variability in CS patient selection and more reproducible imaging methods/criteria for detecting complex aortic plaque.
Abstract TP89: Ldl Levels May Correlate With Intracranial Atherosclerotic Plaque Enhancement
Authors: Sanchez Sebastian , Miller Jacob M , Jones Matthew T , Samaniego Edgar A
Published: February 2023

Introduction:
The enhancement of atherosclerotic plaques after the intravenous administration of gadolinium (Gd) has been correlated with the presence of culprit plaques in patients with acute strokes due to underlying intracranial atherosclerosis (ICAS). A new method to objectively quantify Gd-enhancement was used to monitor plaques over time after an acute stroke. Currently there is no imaging method to accurately monitor atherosclerotic activity.

Methods:
Patients with stroke or transient ischemic attack caused by ICAS were included. Every patient was started on high-dose statins after ictus. 7T MRI images were obtained at baseline and after at least 6 months. LDL levels were obtained at the time of the event and at follow-up. Culprit plaques were identified based on degree of stenosis, presence of positive remodeling and Gd-enhancement. Arterial 3D enhancement maps in the territory of the culprit plaque were generated. Orthogonal signal intensity (SI) probes were expanded into the plaque and parent vessel to generate 3D enhancement color maps. Arterial segment variance (ASV) (SD
2
Arterial segment Baseline T1+Gd
- SD
2
Arterial segment Follow up T1+Gd
) was used to compare the plaque and parent vessel enhancement.

Results:
Five patients underwent baseline and follow-up imaging. The median time between scans was 13.3 (IQR=13.3) months. ASV was strongly correlated with changes in LDL (Rho=0.9, p=0.037). Additionally, Gd-enhancement and plaque burden correlated with levels of LDL (Figure): Gd uptake (Rho=0.7, p=0.22) and plaque burden (Rho=0.67, p=0.22).

Conclusion:
This pilot study demonstrates that high-resolution imaging can be used in determining the response to statins in patients with high atherosclerotic burden. Gd-enhancement and plaque burden correlated with serum values of LDL. 3D enhancement maps and histogram analysis of atherosclerotic plaques are promising tools for evaluating disease activity and response to medical therapy.
Abstract TP93: Ac-aspects And H-aspects: Imaging Scores To Assess Anterior Cerebral Artery Territory And Total Hemispheric Ischemia
Authors: Rodriguez Maria P , Taleb Shayandokht , Lee Jenny J , Liebeskind David S , Saver Jeffrey L
Published: February 2023

Background:
Acute Stroke Prognosis Early CT Scores (ASPECTS) for MCA (original ASPECTS) and PCA (PC-ASPECTS) are staples of modern stroke management. For treatment decision-making in large ischemic core patients (e.g. endovascular thrombectomy and hemicraniectomy), measures of ACA and total hemisphere ischemia are also desirable.

Methods:
We developed ratings for anterior cerebral artery territory (AC-ASPECTS) and total supratentorial hemisphere (H-ASPECTS). The ACA was assigned 3 subregions: A1 - inferior; A2 - anterosuperior; and A3 - posterosuperior (Figure). The 16-point H-ASPECTS score is the sum of the MCA (10 regions), supratentorial PC (2 regions), AC-ASPECTS (3 regions) and anterior choroidal territory (1 region). We rated initial and 24h CT/MR images in patients with ischemic stroke due to ICA, M1 MCA, or ACA occlusions.

Results:
Among 50 consecutive patients, age was 74.7 (±13.9), 60% female, NIHSS 15 (9-20). Occlusion locations were: ICA 36%; M1-MCA 56%; ACA 8%. Treatments included EVT+/- thrombolysis in 72%, IV thrombolysis only in 8%, and hemicraniectomy in 4%. Time from last known well to 1st imaging was 393m (114-851) and 2nd imaging 32h (29-41). ACA abnormality was present in 18% of patients, among whom median AC-ASPECTS were: initial scan median 3 (IQR 3-3); 24h 3 (0-0). On 1st imaging, 8% had A1, 4% A2, and 6% A3 involvement; on 2nd imaging 8.6% had A1, 13% A2, and 13% A3. By occlusion site, H-ASPECTS was: ICA 9 (6-12); M1 MCA 12 (11-13); ACA 15 (12-17). AChA abnormality was present in 2%. Correlation between initial NIHSS and initial imaging score was higher for H-ASPECTS than standard ASPECTS, r = 0.47 vs 0.20.

Conclusions:
AC-ASPECTS and H-ASPECTS expand the scope of AIS imaging scores and increase correlation with presenting deficits. This additional information may improve decision-making in patients with large ischemic cores, including for endovascular thrombectomy and hemicraniectomy.
Figure AC-ASPECTS Regions
Abstract TP95: Utility Of Automated Artificial Intelligence Software In The Analysis Of Ct Perfusion With Acetazolamide Challenge For The Assessment Of Cerebrovascular Reserve In Patients With Cervico-cranial Arterial Stenoses And Occlusions
Authors: Khadem Alsrouji Owais , Marin Horia , Kole Max , Chebl Alex
Published: February 2023

Background:
Cerebrovascular reserve (CVR) assessment is valuable in predicting stroke risk in patients with cranio-cervical stenoses and occlusions. CTP with Acetazolamide challenge (AC) allows a qualitative and quantitative assessment of CVR but is limited by ROI positioning, motion and software. Artificial intelligence (AI) automated software with delay in arrival correction has been validated for the processing of CTP data for acute stroke and may more easily detect abnormal CVR. We sought to compare the results of image-processing with a standard platform (Vitrea™) and AI platform (RAPID™).

Methods:
Retrospective analysis of an IRB approved prospective database of patients who had CTP with acetazolamide (1g IV) who also had a stenosis/occlusion of the internal carotid or middle cerebral arteries was performed. Symptomatic status was defined as recurrent symptoms related to the vessel of interest within 6 months of scan. Two readers, blinded to the clinical scenario, independently reviewed the CTP datasets and identified CBF regional abnormalities and changes post AC using the 2 different platforms. Abnormal CVR was defined as an increase of CBF post AC of <25% of the baseline in the region of interest with Vitrea™, and an expansion of the volume of tissue with CBF<30% using RAPID™. CTP analyses were correlated with the clinical presentation.

Results:
Thirty patients fulfilling criteria received CTP before and after AC. 24 patients (80%) were symptomatic. Vitrea™ detected decrease in CBF pre-AC in 27 patients and worsening CBF value post-AC in 19 patients. 10 Patients had an increase >25% in CBF post AC. Rapid™ detected 5 patients with CBF lesion <30% pre-AC. Expansion of the CBF lesion occurred in 8 patients post-AC with a mean change in volume of 7.7 ml (P-value=0.002). The sensitivity for the detection of poor CVR in patients with recurrent symptoms was 80% (95% CI 59.30 - 93.17) with Vitrea™ and 45% (95% CI 25.55%-67.18%) with RAPID™.

Conclusion:
Automated post processing software with delay in arrival correction algorithm is less sensitive to abnormal CVR and has lower correlation with clinical presentation in this small cohort. Further study is warranted to identify thresholds that may better correlate.
Abstract WMP10: Effect Of Imaging Selection Paradigms On Endovascular Thrombectomy Outcomes In Acute Ischemic Stroke Patients With Large Vessel Occlusion: A Pooled Analysis Of The Devt And Rescue Bt Randomized Clinical Trials
Authors: Miao Jian , Lei Lei , Song Bo , Zhang Xiao , Sang Hongfei , Qiu Zhongming , Wang Shaojun
Published: February 2023

Background and Purpose:
The study aimed to assess the effect of basic imaging (noncontrast computed tomography (NCCT) with or without computed tomographic angiography (CTA)) versus advanced imaging (magnetic resonance imaging (MRI) or computed tomography perfusion (CTP)) on clinical outcomes following thrombectomy in stroke patients with large vessel occlusion (LVO) in the early and extended windows using a pooled analysis of randomized controlled trials.

Methods:
Patients from two randomized controlled trials with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery (M1/M2 segments) were categorized according to baseline imaging modality (basic versus advanced) as well as treatment time window (early: 0-6 hours versus extended: 6-24 hours from last known well to puncture). The primary outcome was the proportion of patients with functional independence (modified Rankin scale score of 0-2) at 90 days. Multivariable Poisson regression analysis was performed to determine the association between imaging selection modality and outcomes after EVT at each time windows.

Results:
A total of 1182 patients were included in this cohort analysis, with 648 in the early (471 with basic imaging versus 177 advanced imaging) and 534 in the extended (222 basic imaging versus 312 advanced imaging) time window. There were no differences in 90-day functional independence between the advanced and basic imaging groups in either time windows (early window: adjusted relative risk, 0.95 (95% confidence interval, 0.80-1.11),
P
=0.49; extended window: adjusted relative risk, 0.98 (95% confidence interval, 0.82-1.17),
P
=0.83).

Conclusions:
In this post-hoc analysis of two randomized clinical trial pooled data involving patients with LVO stroke, there was no association between imaging selection modality and clinical or safety outcomes for patients undergoing thrombectomy in either the early or extended windows. Our study adds to the growing body of literature simpler imaging paradigms to assess thrombectomy eligibility across both the early and extended time windows.
Abstract WMP103: Proteome-wide Mendelian Randomization Screen Identifies Circulating Protein Mediators Of Early-onset Ischemic Stroke
Authors: Chong Michael , Zhu William , Cole John W , Kittner Steven J , Mitchell Braxton D , Pare Guillaume ,   Stroke Genetic Network and Early Onset Stroke Consortium
Published: February 2023

Objective:
Discover blood proteins mediating risk of early-onset ischemic stroke (IS) via Mendelian Randomization (MR) analyses.

Background:
About 10-15% of IS affect young adults (18-50 years) and, in contrast to declining rates in older individuals, IS incidence has risen in the young. Thus, new therapies tailored to early-onset IS are of urgent need.

Design/Methods:
We conducted a proteome-wide MR screen of 653 blood proteins for susceptibility to early-onset IS (18-65 years) and its subtypes (cardioembolic stroke, large artery atherosclerosis, small artery occlusion, other stroke, and undetermined strokes) using our previous framework (
Circulation
, 2019). cis-pQTLs (LD r
2
<0.01; P<0.01) were derived from a meta-analysis of five pQTL GWAS (N≤20,509). Corresponding genetic effects on early and late-onset IS were derived from the Early-Onset Stroke Consortium (N
case
= 16,851; N
control
= 32,473) and Stroke Genetics Network (SiGN) GWAS (N
case
= 9,272; N
control
= 25,124), respectively. MR analyses were conducted using inverse variance weighted, weighted median, and MR-EGGER methods.

Results:
Previously reported biomarkers were found to mediate risk of early-onset IS including ABO (OR
all stroke
=1.10 per SD increase in genetically predicted levels; 95% CI, 1.05-1.15; P=2.8x10
-5
) and MMP12 (OR
all stroke
=0.87; 95% CI, 0.82-0.93; P=2.1x10
-5
). In addition, at Bonferroni significance, we identified two new mediators of early IS: vascular endothelial growth factor 2 (KDR
;
OR
small artery occlusion
=1.94; 95% CI,1.6-2.4; P=2.1x10
-9
) and urokinase-type plasminogen activator (PLAU; OR
undetermined stroke
=3.08; 95% CI,1.9-5.2; P=1.3x10
-5
). Genetically predicted levels of these proteins were not significantly associated with late-onset IS (> 65 years), and MR effect estimates differed significantly between early vs. late-onset IS for KDR (I
2
=96; heterogeneity P=9.7x10
-7
) and PLAU (I
2
=85; het. P=0.01).

Conclusion:
While targeting known protein mediators for IS at all ages may help reduce risk of early-onset IS, there are likely additional distinct etiological mechanisms precipitating premature IS that also may warrant specific therapeutic intervention.

Study Supported By:
NIH R01NS086905, R01NS100178, R01NS105150
Abstract WMP104: Mortality And Recurrence Within 1 Year After Ischemic Stroke For Urban Vs Rural US Medicare Beneficiaries
Authors: Leifheit Erica C , Wang Yun , Goldstein Larry B , Lichtman Judith H
Published: February 2023

Background:
Approximately 14% of the US population resides in rural areas, which have higher rates of chronic disease and are often medically underserved. We compared 1-year outcomes after ischemic stroke for Medicare beneficiaries living in urban vs rural areas.

Methods:
We identified all Medicare fee-for-service beneficiaries aged ≥65 years discharged alive from US acute-care hospitals with ischemic stroke in 2015 to 2017. Patients were followed up to 1 year through 2018 for death or ischemic stroke recurrence and categorized according to geographic remoteness of their residence using the Rural-Urban Community Area codes. We balanced patient characteristics between the rural/urban categories using stabilized inverse probability weights (IPW) based on patient demographic and clinical characteristics. We created adjusted Kaplan-Meier curves based on the IPW and fit Cox models to assess differences in 1-year all-cause mortality and recurrent stroke weighted by the IPW and accounting for competing risks.

Results:
There were 536,930 stroke patients (32,635 isolated rural, 40,240 small rural, 66,320 large rural, 397,735 urban; mean age 79.0 years, 54.7% women, 82.5% White). For isolated rural, small rural, large rural, and urban residents, 1-year adjusted mortality rates were 24.1%, 24.6%, 24.7%, and 22.9%, and 1-year stroke recurrence rates were 8.0%, 7.8%, 7.9%, and 8.1%, respectively. Compared with urban residents, isolated rural (HR 1.07, 95% CI 1.04-1.09), small rural (1.09, 1.07-1.12), and large rural (1.10, 1.08-1.12) residents had greater risk of death within 1 year after stroke, but there was little difference in recurrence (Fig. A). Urban residents had the lowest mortality across regions, but there was variation among the rural subcategories and for recurrence in region-stratified analyses (Fig. B).

Conclusions:
Ischemic stroke patients living in urban areas had a lower risk of mortality within 1 year compared with those living in more rural areas.
Abstract WMP106: Sex-stratified Transethnic GWAS Meta-analysis Identifies Novel Candidates For Early Onset Ischemic Stroke
Authors: Tomppo Liisa , Gaynor Brady , Putaala Jukka , Strbian Daniel , Kõrv Janika , Vibo Riina , de Leeuw Frank-Erik , Boncoraglio Giorgio , Pare Guillaume , Markus Hugh , Rundek Tatjana , Rexrode Kathryn M , Wassertheil-Smoller Sylvia , Rosand Jonathan , Havulinna Aki S , Malik Rainer , Mitchell Braxton D , Kittner Steven J ,   Early Onset Ischemic Stroke Consortium
Published: February 2023

Background:
Early onset ischemic stroke (IS) affects males and females unequally, but the etiologic background of the sex differences remains inadequately understood. We hypothesize that stratifying GWAS by sex provides an opportunity to 1) identify loci that shed light on mechanisms and pathways relevant to sex specific effects in IS and 2) discover novel IS loci.

Methods:
We performed a sex-stratified transethnic GWAS meta-analysis in 6,879 female IS cases and 11,264 male cases < 60 years-old and > 700,000 sex-matched controls from the Early Onset Stroke Genetics Consortium. We tested for difference (p-diff) between the men- and women-specific beta-estimates with corresponding standard errors using the t statistics.

Results:
We found genome-wide significant evidence for association (p < 5 х 10
-8
) at a locus near
NYAP2
for females (chr2:225661726:C:CT, p = 2.11 х 10
-8
, OR = 1.38, p-diff = 1.69 х 10
-4
) and in
PIAS4
for males (chr19:4013652:C:CA, p = 6.29 х 10
-9
, OR = 0.85, p-diff = 0.02) in transethnic analysis.
NYAP2
has previously shown suggestive evidence for association with early onset menopause.
PIAS4
, a candidate gene for migraine, has shown sex-specific expression levels in migraine patients compared to controls. Additional loci with suggestive evidence (p < 1 х 10
-6
) for association in a sex-dependent manner included
MMP1-MMP3
-
MMP12
, a previously known stroke locus, for males (chr11:102822455:A:G, p = 3.99 х 10
-7
, OR = 1.17, p-diff = 0.02), and a novel stroke locus near
TMX1
, a transmembrane platelet protein, for females (chr14:51193174:G:C, p = 4.15 х 10
-7
, OR = 1.76, p-diff = 4.08 х 10
-3
). The known early onset IS locus
ABO
did not show evidence for sex-specific association despite suggestive association in the male stratified analysis (chr9:133274295:A:T, p = 3.15 х 10
-7
, OR = 1.17, p-diff = 0.81).

Conclusions:
We identified potential novel stroke loci and evidence for sex differences at other biologically relevant loci by stratifying GWAS by sex. To our knowledge, our cohort represents the largest early onset IS GWAS cohort to date. However, our findings require verification in large sample sizes and also evaluation in older onset IS. Sex-specific association analysis is a potentially useful tool for characterizing the genetic basis of early onset IS.
Abstract WMP107: Temporal Trends In Public Awareness Of Stroke: 1996-2021
Authors: Robinson David , Khoury Jane C , Ding Lili , Rademacher Eric , Alwell Kathleen , Broderick Joseph P , Stanton Robert J , Kissela Brett M , Kleindorfer Dawn O
Published: February 2023

Background:
Knowledge of stroke risk factors (RF) and warning signs (WS) may improve adherence to primary stroke prevention and encourage more rapid presentation after symptom onset. As a result, improving stroke knowledge has been a major public health focus. We sought to study trends in stroke knowledge between 1996 and 2021 in a well-defined population.

Methods:
Surveys were conducted in 1996, 2000, 2005, 2011, 2016, and 2021 in the 5-county Greater Cincinnati Northern Kentucky region, a population of 1.3 million that reflects the USA in terms of Black race, income, and educational attainment. Respondents were selected to reflect the age, race and sex distribution of the local ischemic stroke population. Potential subjects were contacted using random-digit dialing (with adjustment for cell phone use after 2005) and asked open-ended questions regarding stroke WS and RF knowledge. Correct answers for all years were determined based upon current AHA guidelines and public health messaging. Trends in knowledge were then evaluated over time adjusting for age, Race, sex, and education. Multiple logistic regression models and a cumulative model were used for analysis.

Results:
Over the 25-year period, 12,322 surveys were completed. After adjustment for age, sex, Race, and education, RF and WS knowledge significantly increased between 1996 and 2021 (P<0.0001), but this was not consistent across years (Figure). The percentage of participants that could identify at least two WS improved significantly in 2000 and then again in 2011. Stroke WS knowledge was then stagnant in 2016 and worsened slightly in 2021. Knowledge of at least two RFs steadily improved from 1996 to 2011, but then declined modestly in 2016 and was stagnant in 2021.

Discussion:
While stroke RF and WS knowledge has overall improved since 1996, knowledge remains suboptimal and some gains may have been lost in recent years. More research on the most effective methods for improving stroke awareness is needed.
Abstract WMP11: Health-related Quality Of Life After Thrombolysis In Acute Stroke: Results From The Act Trial
Authors: Sajobi Tolu , Ademola Ayoola , Arimoro Olayinka I , Singh Nishita , Bala Fouzi , Almekhlafi Mohammed , Deschaintre Yan , Appireddy Ramana , Gubitz Gord J , Tkach Aleksander , Catanese Luciana , Medvedev George , Shankar Jai J , Manosalva Alzate Herbert A , Imoukhuede Oje , Kenney Carol C , Sehgal Arshia , Zhang Qiao , Doram Craig , Zafar Atif , Moreau Francois , Williams Heather , Buck Brian H , Hill Michael D , Swartz Richard H , Menon Bijoy K ,   the AcT Trial Investigators
Published: February 2023

Background and aims:
Recent evidence from thrombolysis trials indicate the non-inferiority of the Tenecteplase (TNK) to the Alteplase (TPA) with respect to functional outcomes in acute stroke patients. This study examines the predictors of patient-reported health-related quality of life (HRQOL) in acute stroke patients who received thrombolysis therapy.

Methods:
Data were used from all acute stroke patients included in AcT, a pragmatic, registry-linked randomized trial comparing TNK with TPA. HRQOL at 90-day post-randomization was assessed using the EuroQol-5D-5L (EQ-5D) visual analogue scale (VAS). Based on the Canadian norms, health state utilities were estimated from the EQ-5D items using the EQ-5D time trade-off approach. Tobit regression model and linear mixed-effects regression were used to evaluate the adjusted effect of type of treatment on health utility scores and VAS score, respectively.

Results:
Of the 1262 patients included in this analysis, 647(51.3%) were administered the TNK, 584(46.3%) were female, and 380(30.1%) were greater than or equal to 80 years old. There was no significant adjusted effect of the type of thrombolysis on health utility scores (adjusted beta coefficient [95%CI] = 0.029 [-0.001, 0.062]), but patients who received TNK reported higher adjusted VAS scores than those that received TPA [adjusted beta coefficient [95%CI] = 2.1 [-0.29, 4.49]). Older age (p < 0.01), female sex (p = 0.01), higher NIHSS score (p < 0.01) were associated with lower health utilities and VAS scores.

Conclusion:
There is no differential effect of the type of thrombolysis on patient-reported global HRQOL and health state utilities of acute stroke patients. Disparities in HRQOL were mainly explained by sex, age, and disease severity.
Abstract WMP110: Vascular Endothelial Growth Factor C Confers Neuroprotection And Ameliorates Ischemic Stroke Outcomes
Authors: Simoes Braga Boisserand Ligia , Lee Seyoung , Bouchart Jean , Medeiros Geraldo Luiz Henrique , Sanganahalli Basavaraju , Eichmann Anne , Sansing Lauren H , Benveniste Helene , Hyder Fahmeed , Thomas Jean-Léon
Published: February 2023

Meningeal lymphatic vessels (MLVs) promote clearance and immune surveillance of central nervous system (CNS)
1
tissue. Vascular Endothelium Growth Factor-C (VEGF-C) regulates meningeal lymphatic growth and has shown therapeutic potential for neurological disorders such as cognitive aging
2
and brain tumors
3
, while stroke outcome is worsened by impaired MLV growth
4
. We hypothesized that VEGF-C delivery into the cerebrospinal fluid (CSF) might benefit stroke injury repair and investigated the effects of VEGF-C overexpression on brain fluid drainage, brain gene expression, and stroke outcome in adult mice. Adult male C57BL/6J mice received VEGF-C-expressing adeno-associated virus (AAV) or control AAV into CSF (
n
= 10 per condition). Four weeks after AAV delivery, we used contrast-enhanced magnetic resonance imaging (MRI) for real-time tracking of a CSF-injected gadolinium-based solute tracer and quantifying CSF drainage. VEGF-C pretreatment did not alter glymphatic drainage and CSF efflux through the cribriform plate but increased deep cervical lymph nodes volume and drainage. Single nucleus RNA sequencing of forebrain cells isolated from AAV-VEGF-C or -control pretreated mice (
n
= 5 per condition) revealed that VEGF-C upregulated the Brain-derived Neurotrophic Factor (BDNF) signaling pathway in brain interneurons. Finally, in a mouse model of ischemic stroke induced by 60 min of transient middle cerebral artery occlusion (tMCAO), AAV-VEGF-C pretreatment reduced lesion volume measured by MRI, improved motor performances evaluated using Neuroscore (at days 3 and 7 post-stroke) and Hanging wire test (at day 3 post-stroke) and increased brain expression of BDNF and NGF transcripts on day 7 post-stroke. Intra-CSF AAV-VEGF-C delivery before stroke can thus promote CNS-derived fluid drainage, induce neuroprotection, and protect against ischemic damage.
Abstract WMP118: Sex-specific And Dose-dependent Effects Of Drag-reducing Polymers On Post-traumatic Ischemia In Rats After Traumatic Brain Injury Of Different Severity
Authors: Bragin Denis E , Bragina Olga , Kameneva Marina , Divani Afshin A , Nemoto Edwin M
Published: February 2023

Introduction:
Previously, we showed that drag-reducing polymers (DRP) improve hemodynamics in rat models of brain injury (TBI). Here we examined the dose- and sex-dependent DRP effects on post-TBI ischemia.

Methods:
In-vivo 2-photon microscopy over the rat parietal cortex was used to monitor the effect of DRP on microvascular perfusion and tissue oxygenation (NADH) and blood-brain barrier permeability. Lateral fluid-percussion TBI (1.5 ATA-moderate or 2.5 ATA-severe, 100 ms) was induced after baseline imaging and followed by 4 hours of monitoring. DRP injected at 1, 2, or 4 ppm. Data analysis was done by GraphPad Prism 7.

Results:
Moderate TBI progressively decreased microvascular circulation and hypoxia in the pericontusion zone (p<0.05). The i.v. injection of DRP increased near-wall flow velocity and flow rate in arterioles, leading to an increase in the number of erythrocytes entering capillaries, enhancing capillary perfusion in a dose-dependent manner without distinguishable difference between males and females (p<0.01). The severe TBI resulted in intracranial pressure increase (31±3.2 mmHg, p<0.05), leading to microcirculation redistribution to non-nutritive microvascular shunt (MVS) flow and stagnation of capillary flow. Tissue hypoxia was more prominent, especially in male rats; the pericontusion zone was 25±5.2% larger than after moderate TBI (p<0.01). Both were reverted by DRP in a dose-related manner with better efficiency in females (p<0.01). After severe TBI, BBB degradation was faster and more prominent. DRP was more efficient in attenuating the progression of permeability increase in moderate TBI (p<0.05).

Conclusion:
DRP at 4 ppm was most efficient, with a better effect on female rats. Supported by NIH/NINDS R01NS112808
Abstract WMP17: Impact Of Nursing Education And Implementation Of Evidenced Based Dysphagia Screening
Authors: Stebelton Jeanette
Published: February 2023

Introduction:
Dysphagia is a complication experienced in patients with acute stroke. Complications can lead to aspiration pneumonia, swallowing difficulties, inadequate nutrition, and increased healthcare costs. Guidelines for stroke care require that stroke patients must be screened for dysphagia before eating, drinking, or receiving oral medications. Registered Nurses (RNs) play a vital role in screening for dysphagia and when provided with the appropriate education are better equipped to assess for dysphagia risk and intervene as needed. The purpose of the study is to determine whether RNs at a hospital in a Midwestern State, who complete a dysphagia screening education, demonstrated knowledge acquisition prior to implementing the Yale Swallow Protocol (YSP). The YSP is an evidenced-based screening tool that identifies aspiration risk and when passed, can recommend oral diets without the need for further instrumental dysphagia testing. Implementation of the YSP required RN education project to increase knowledge and competency for dysphagia screening.

Method:
This summative study utilized a tracking tool that compared results of a ten-item pre-test and post-test. Summative evaluation was directly related to the identified learning objectives and measured RNs knowledge acquisition.

Results:
Fifty-seven subjects complete the study. The results were analyzed via paired t test, which showed a statistically significant difference between the pre-test and post-test scores (t = 6.254, df = 56, p = .000), which suggest that the educational activity had a positive impact on learner knowledge. This education promotes positive social change by increasing RNs’ knowledge, confidence, and competence when caring for stroke patients, thus increasing patient quality of care.

Conclusion:
Project findings showed dysphagia screening education had an impact on knowledge acquisition. In addition, completion of the dysphagia screen education provided the necessary tools and resources to implement use of the YSP at the specialty care hospital. In addition, training will help prevent disparities in the way patients are screened for dysphagia.
Abstract WMP2: Acute Stroke Treatment In Patients With Pre-exiting Disability: A Secondary Analysis Of The BEST-MSU Trial
Authors: Pirlog Bianca O , Jacob Asha P , Yamal Jose-Miguel , Parker Stephanie , Rajan Suja S , Bowry Ritvij , Czap Alexandra L , Bratina Patti , Gonzalez Michael O , Singh Noopur , Wang Mengxi , Zou Jinhao , Gonzales Nicole R , Jones William J , Alexandrov Anne W , Alexandrov Andrei V , Navi Babak B , Nour May , Spokoyny Ilana , Mackey Jason S , Fink Matthew E , Saver Jeffrey L , English Joey D , Barazangi Nobl , Volpi John J , Rao Chetan P , Kass Joseph S , Griffin Laura , Persse David , Grotta James C
Published: February 2023

Background:
Few data exists on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials.

Methods:
A pre-specified subgroup analysis of tPA-eligible patients with PD enrolled in a prospective multicenter trial of Mobile Stroke Units (MSUs) vs standard management by emergency medical services (EMS). All patients had baseline mRS scores. Co-primary outcomes were mean utility-weighted modified Rankin Scale score (uw-mRS) and return to baseline mRS at 90 days. Linear and logistic regression models compared outcomes in patients with vs without PD, and patients with PD treated by MSU vs EMS. Time metrics, safety, quality of life, and health-care utilization were also compared.

Results:
Of 1047 patients, 254 had baseline mRS
>=
2 (159 MSU, 95 EMS; 31% mRS 2, 52% mRS 3, 17% mRS 4). Compared to patients without disability, patients with PD were older, had higher NIHSS, more comorbidities, less often lived at home, were treated slower, and had less thrombectomy. Patients with PD had worse 90-day uw-mRS (0.39 vs 0.80), higher mortality, more health-care utilization and worse quality of life than patients without PD. However, rates of symptomatic intracranial hemorrhage and final diagnoses of stroke mimics were similar between groups, and 52% of patients with PD returned to their baseline mRS. Patients with PD treated within the first hour had better 90-day uw-mRS than those treated later (0.48 vs 0.36, p=0.01). Comparing patients with PD treated by MSU vs EMS, time from last-known-well to tPA bolus was shorter (82 vs 111 min), and 24% vs 0% were treated in the first hour. Among patients with PD, MSU patients had non-significantly better 90-day uw-mRS (0.41 vs 0.35, p=0.09) and higher rate of returning to baseline mRS (56% vs 44%, p=0.09) than EMS patients. There was no interaction between either time to treatment (p=0.24) or MSU vs EMS group assignment (p= 0.42), 90-day uw-mRS, and PD vs no disability status.

Conclusion:
Although outcomes after stroke are less favorable in patients with vs without PD, in a large, controlled trial, we found no interaction between baseline disability and the benefit of MSU treatment. Our data support the earliest treatment of acute stroke patients regardless of premorbid functional status.
Abstract WMP20: Forget The Drip, Just Bolus And Ship: A Regional Initiative To Shift From Alteplase To Tenecteplase And Its Effect On Door-in-door-out Time
Authors: Onyan Joshua L , Makaron Arkadiy , Schleier Jennifer , Latorre Julius Gene S , Vallelunga Michelle F , Veinot Patricia , Seabury Robert
Published: February 2023

Background and Purpose:
In order to provide efficient and effective stroke care, The American Stroke Association recommends establishing stroke systems of care. Standardizing stroke care from a regional approach ensures patients receive consistent, evidence-based care. Many community and critical access hospitals lack resources needed for rapid transfer to the regional comprehensive stroke center (CSC) after treatment of an acute ischemic stroke. Single-bolus administration of IV tenecteplase (TNK) in community and critical access hospitals allows for immediate transfer of patients without the necessity of an hour-long infusion. There is supporting evidence for the use of TNK as an alternate for alteplase (ALT) for the treatment of suspect ischemic stroke. The purpose of this poster is to demonstrate the effectiveness of a regional initiative in the transition to the use of TNK over ALT to improve door-in-door-out (DIDO) times.

Methods:
CSC leadership held meetings and educational sessions with key stakeholders from referring hospitals across the region to discuss the feasibility and advantages of transitioning to TNK for stroke treatment. A TNK toolkit was provided which included dosing and safety information, sample order sets, cost-effectiveness, and consent information. DIDO times of hospitals using TNK were compared to those hospitals using alteplase over an 8-month period.

Results:
There were 37 patients included in the analysis, with 21 receiving ALT and 16 receiving TNK over the study period. Median DIDO times for ALT patients were 195.5 minutes while median DIDO times for TNK patients were 178.5 minutes. There were no major complications noted.

Conclusions:
DIDO times for TNK-treated patients appear to be less than those treated with ALT. As more regional hospitals begin to use TNK for suspected stroke, continued monitoring of DIDO times will be required. Additional analysis of DIDO data from transferring hospitals transitioned to TNK is needed. Regional change in stroke systems of care impacting multiple hospitals across a wide geographic area is feasible and impacts the efficiency of treatment. Additional study is needed to determine if the effect is sustainable and results in improved outcomes.
Abstract WMP23: Dynamic Imaging Of Blood Coagulation Within The Hematoma Of Patients With Acute Intracerebral Hemorrhage
Authors: Haque Muhammad E , Boren Seth , Schneider Kerry , Mills James A , Fraser Stuart M , Bach Ivo , Hariharan Praveen , Zelnick Pamela , Guerra Castanon Felix , Naveed Asim , Tariq Muhammad B , Arevalo Octavio D , Parekh Maria , Zhao Xiurong , Sitton Clark , Aronowski Jaroslaw A , Grotta James C , Savitz Sean I
Published: February 2023

Objective:
To serially quantify the blood coagulation within hematoma of patients with hyper-acute intracerebral hemorrhagic (ICH) stroke using non-invasive quantitative susceptibility mapping (QSM) MRI.

Introduction:
A blood clot is a combination of aggregated red blood cells, fibrin, platelets, hemosiderin, and other cell debris. An accurate evaluation of clot formation within hematoma could advance the clinical management of hematoma expansion, blood pressure management, and reversal of anticoagulants. Post-ICH hemolysis changes the heme iron oxidation state from oxy to deoxyhemoglobin (deoxy-Hb) resulting in unpaired iron electrons on aggregated RBC’s deoxy-Hb inducing magnetic susceptibility (χ). Therefore, a region with a higher number of aggregated RBC deoxy-Hb molecules, the dominant component of clots, will exhibit a higher positive χ susceptibility. We hypothesized that coagulated blood within hematoma will exhibit a higher positive χ in comparison to the non-clotted which can be quantified using quantitative susceptibility mapping (QSM), which is an advanced MRI image-processing algorithm.

Methods:
For proof of concept, we measured susceptibilities of 5 human blood phantoms with various percentages of the clot. Twenty-four patients with acute spontaneous ICH were enrolled and serially imaged 3 times within 12-24 (T1), 36-48 (T2), and 60-72(T3) hours of last known well (LNW). A 3D anatomical and multi-echo gradient echo images were obtained using a 3T MRI system. Hematoma and edema volumes were segmented and used as a region of interest (ROI). The rate of coagulation was assessed by measuring the change in susceptibilities within the hematoma.

Results:
The blood phantom exhibited a linear relationship between the percent coagulation and χ (R
2
=0.91). The QSM maps showed a significant increased in hematoma susceptibility over time (T1=0.29 ± 0.04, T2=0.36 ± 0.04, T3= 0.45 ± 0.04 ppm, p<0.0001). The overall average rate of coagulation was 0.00290 ± 0.0029 ppm per hour. No significant change in hematoma volume (18.9 ±3.1 cc) over time. A significant edema growth over time (T1=25.3 ± 3.6, T2= 28.1 ± 3, T3= 32.37 cc, p<0.05).

Conclusion:
In conclusion, we present novel surrogate imaging markers of coagulation within the hematoma of ICH.
Abstract WMP28: Ethnic Differences In Use Of Rehabilitation In The First 90 Days Following Incident Stroke
Authors: Lisabeth Lynda D , Kwicklis Madeline , Almendarez Elizabeth , Prvu-Bettger Janet , Morgenstern Lewis B
Published: February 2023

Introduction:
Mexican Americans (MAs) have worse stroke outcomes than non-Hispanic whites (NHWs). One possible explanation is that MAs receive less intense rehabilitation than NHWs. Our objective was to examine ethnic differences in use and type of rehabilitation in the first 90-days following stroke.

Methods:
Stroke cases were identified from the population-based Brain Attack Surveillance in Corpus Christi Project from Oct 2019-Oct 2021 and followed for 90 days for self-reported use of post-acute rehabilitation care. Sociodemographics, risk factors, stroke severity and treatment were ascertained from interviews and medical records. Functional outcome and depression were assessed at 90 days. Propensity score (PS) methods were used to balance characteristics by ethnicity and PS scores and other covariates were included in a logistic regression model of the association between ethnicity and the primary outcome of use of any rehabilitation.

Results:
Five hundred fifty-four stroke patients were included, with 66% MA and 49% women. MAs were younger, had lower education and income, worse pre-stroke function, more comorbidities, greater average BMI and worse functional outcome and depression at 90-days than NHWs. One-third of participants did not receive any rehabilitation. MAs (66.9%) were more likely to use any rehabilitation following stroke than NHWs (55.9%; p-value=0.01). After adjustment, MAs were 1.9 times (95% CI: 1.2-2.9) more likely to use any rehabilitation than NHWs. MAs were more likely to use outpatient (11.3% vs 4.8%) and home health rehabilitation (38.0% vs 29.8%) than NHWs, while no differences were noted in use of rehabilitation in inpatient or skilled nursing facilities.

Conclusion:
A high proportion of stroke survivors report no rehabilitation in the first 90 days following stroke. MAs report greater use of less intense forms of rehabilitation than NHWs despite worse outcomes. Future research should investigate barriers to use of more intense rehabilitation care, particularly in MAs, with the goal of maximizing recovery and reducing ethnic disparities.
Abstract WMP29: Sex Differences On The Importance Of Multimorbidity In Post-stroke Disability:the Taiwan Stroke Registry
Authors: Egle Marco , Wang Wei-Chun , Fann Yang C , Gottesman Rebecca F ,   Taiwan Stroke Registry Investigators
Published: February 2023

Background:
Experiencing a clinical stroke may further aggravate the clinical condition of patients with multimorbidity and pose significant challenges regarding recommended poststroke therapies. However, there is limited evidence regarding the impact of multimorbidity on long-term disability in stroke patients, or whether any associations differ by sex.

Hypotheses:
Clusters of multimorbidity are associated with post-stroke disability. The association may depend on sex membership.

Methods:
In the Taiwan Stroke Registry study, 9818 patients with their first-ever recorded ischemic stroke were examined. Employing a hierarchical clustering approach, clusters of multimorbidity were generated based on 16 risk factors and were characterized using the observed/expected prevalence ratio ≥1.5 and the prevalence exclusivity measure ≥25%. Post-stroke disability was assessed using the mRS and categorized into less (mRS <3) vs. more disability (mRS ≥3) over 12 months. The association between clusters of multimorbidity and post-stroke disability adjusted for age, sex, education, and stroke severity (NIHSS) was determined using logistic regression models, overall and stratified by sex.

Results:
Patients with a cluster profile of diabetes, peripheral artery disease and uremia had more disability than patients with a healthier cluster profile (Table 1). The association only remained significant in males, who had a higher multimorbidity burden, but not in females who more frequently had more severe strokes and more severe post-stroke disability.

Conclusion:
Patients with multimorbidity involving diabetes, peripheral artery disease and uremia have greater post-stroke disability and may require a more targeted rehabilitative approach. Certain clusters of multimorbidity may be more important for long-term post-stroke disability outcomes in males than in females.
Abstract WMP30: Expansion Of Plasma Micrornas Over The First Month Following Human Stroke
Authors: Edwardson Matthew A , Shivapurkar Narayan , Li Xin , Khan Muhib , Smith Jamal , Giannetti Margot L , Fan Ruzong , Dromerick Alexander W
Published: February 2023

Introduction:
Stroke induces changes in plasma microRNA (miRNA) expression in the first 24hrs post-injury, but few have characterized miRNA expression during the early recovery phase.

Hypothesis:
We hypothesized that plasma miRNA expression would evolve over the first month post-stroke with fewer significantly altered miRNAs over time as inflammation and edema resolve.

Methods:
Longitudinal samples were collected 5, 15, and 30 days post-stroke from 2 studies (BIOREC and MORSE, n=55 combined at each time point) and compared to controls matched for age, sex, race and cardiovascular comorbidities. Stroke samples collected on average around day 15 from a second study (CPASS, n=48) were also compared to matched controls and used as a validation cohort. MiRNA expression was determined with OpenArray qRT-PCR quantifying 758 miRNAs. Significant miRNAs had a corrected p-value less than 0.05 and fold-change greater than |1.5|.

Results:
Eight miRNAs remained significantly altered across all 3 time points in the discovery cohort and in the day 15 validation cohort (decreased expression compared to controls: miR-101-3p, miR-107, miR-16-2-3p, miR-19a-3p, miR-19b-3p, and miR-26b-5p; increased expression: miRNA-199a-3p and miR-652-3p). The number of significant miRNAs more than doubled from post-stroke day 5 to days 15 and 30 (19, 53, and 45 miRNAs respectively in BIOREC/MORSE, 49 miRNAs at day 15 in CPASS). At day 5 most significant miRNAs (14/19) showed decreased expression compared to controls whereas by day 30 most demonstrated increased expression (36/45). Many of the significant miRNAs, including miR-107 and miR-652-3p, and many others at days 15 and 30 were enriched in brain or CSF in prior studies.

Conclusions:
While several miRNAs show significant change in expression consistently from 5 to 30 days post-stroke, there is also an expansion of significant miRNAs at days 15 and 30. This expansion includes many miRNAs enriched in brain or CSF and could represent a shift from inflammation to neural repair processes, but this requires further study.
Abstract WMP32: Changes In Word Frequency And Articulatory Complexity In Aphasic Discourse Over The First 6 Months After Stroke
Authors: Molinaro Christina , Bunker Lisa , Kelly Catherine , Vitti Emilia , Hillis Argye E
Published: February 2023

Most people with aphasia (PWA) improve in content of discourse over the first 6 months of stroke, but the extent to which increased content is compensatory, by learning to use more frequent or less complex words, is unknown. We hypothesized that PWA who improve in content units (CU; concepts produced by healthy speakers in describing the picture) in picture description show an increase in word frequency and decrease in articulatory complexity from acute stroke to 3 and 6 months.

Methods:
PWA <5 days of left hemisphere ischemic stroke (n=35) and age-matched controls (n=48) described the NIHSS picture. Patients were retested at 3 and 6 months post-stroke. We evaluated CU, articulatory complexity (https://unccard.shinyapps.io/shiny-woRdcomplex-2/) and word frequency (log10 frequency among 51 million words+1) each time. We used 2-tailed t-tests to compare groups and paired t-tests to evaluate changes from 0 to 3 and from 0 to 6 months after stroke.

Results:
Compared to controls, PWA produced fewer CU (mean 19.4 vs 47.6; t (df81) = 7.9; p<0.00001), with lower articulatory complexity (mean 3.0 vs 3.5; t (df81) = 2.8; p=0.006) and lower frequency (3.0 vs 3.3; t(df81) = 2.1; p=0.04) acutely. The 20 participants who improved in CU at 3 months showed an increase in word frequency at 3 months (mean 2.7 to 3.4; t (df19)= -2.0, p= 0.03), while those who failed to improve in CU showed no change. The 19 patients who improved at 6 months also tended increase in word frequency (from 3.0 to 3.5; t (df18)= -1.6; p= 0.07), while those who failed to improve showed a decrease (from 3.4 to 2.7; ns). Those who improved in CU showed an increase in articulatory complexity (mean 2.7 to 3.5, t(df18)= -2.3; p=0.03) at 3 months and 6 months (mean 3.3). Those who failed to improve in CU showed the opposite trend toward decrease in complexity (mean 3.3 acutely, 3.1 at 3 months, and 2.4 at 6 months; ns).

Conclusions:
Improved content in discourse by aphasic individuals over the first 6 months after stroke may in part reflect compensation by selecting more frequent words or increased function words (e.g. prepositions - which are high frequency) to describe a picture. Those who improve in content show an increase in articulatory complexity of words, indicating that increased complexity reflects improvement.