bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP119: CD13 Facilitates Immune Cell Migration and Aggravates Acute Injury but Promotes Chronic Post-Stroke Recovery
Authors: Chauhan Anjali , Nguyen Justin , Mohan Eric , Pandya Gargee , Tan Chunfeng , Kofler Julia , Shapiro Linda , Marrelli Sean P
Published: February 2024

Introduction:
Acute stroke leads to the activation of myeloid cells. Activated myeloid cells express CD13, which facilitates their migration into the site of injury. Chronically after stroke, repair processes, including angiogenesis, are activated and enhance post-stroke recovery. However, angiogenic blood vessels which play a role in recovery also express CD13. Overall, the specific contribution of CD13 to acute and chronic stroke outcomes is unknown.

Methods:
CD13 expression was estimated in mice and humans after the ischemic stroke. Young (8-12 weeks) male wild-type (WT) and global CD13 knockout (KO) mice were used for this study. Mice underwent 60 minutes of middle cerebral artery occlusion (MCAO) followed by reperfusion. For acute studies, the mice were euthanized at either 24- or 72 hours post-stroke. For chronic studies, the Y maze, Barnes maze, and the open field were performed on day 7 and day 28 post-stroke. Mice were euthanized at day 30 post-stroke and the brains were collected for assessment of inflammation, white matter injury, tissue loss, and angiogenesis. Flow cytometry was performed on days 3 and 7 post-stroke to quantify infiltrated monocytes and neutrophils and CXCL12/CXCR4 signaling.

Results:
Brain CD13 expression and infiltrated CD13
+
monocytes and neutrophils increased acutely after the stroke. The brain CD13
+
lectin
+
blood vessels increased on day 15 after the stroke. Similarly, an increase in the percentage area CD13 was observed in human stroke patients at the subacute time after stroke. Deletion of CD13 resulted in reduced infarct volume and improved neurological recovery after acute stroke. However, CD13KO mice had significantly worse memory deficits, amplified gliosis, and white matter damage compared to WT animals at chronic time points. CD13KO mice had an increased percentage of CXCL12
+
cells but a reduced percentage of CXCR4
+
cells and decreased angiogenesis at day 30 post-stroke.

Conclusions:
CD13 is involved in the transmigration of monocytes and neutrophils after stroke, and acutely, led to decreased infarct size and improved behavioral outcomes. However, loss of CD13 led to reductions in post-stroke angiogenesis by reducing CXCL12/CXCR4 signaling.
Abstract WMP120: MicroRNAs as a Therapeutic Target to Reduce Microglial Activation After Post-Stroke Social Isolation
Authors: Banerjee Anik , Mooz Patrick , Zhang Euan , Lee Juneyoung , Venna Venugopal R , McCullough Louise D
Published: February 2024

Introduction:
Loneliness and social isolation (SI) are associated with increased risk of stroke and other vascular disorders, along with all-cause mortality. However, it is unknown what mechanisms mediate how social factors affect stroke recovery.

Methods:
To investigate the negative effects of post-stroke SI on brain miRNA profiles, aged (18-20 months) C57BL/6 male mice were utilized. Three days following a 60-minute transient right middle cerebral artery occlusion (MCAO), mice were randomly assigned to pair housing (PH) or single housing (SI). At post-stroke timepoints (specifically day 3 after the stroke), the infarct was equal between groups, reducing the possibility of differential effects resulting from different infarct sizes. At two-time intervals (post-stroke SI D4 and D27), temporal miRNA profiling of the ipsilateral hemisphere was performed.

Results:
Distinct miRNA candidates were significantly altered in post-stroke SI, within the brain across both acute and chronic time points (n=4/grp, FDR adjusted *p<0.05). MiR-10a-5p and miR-10b-5p were observed to have crucial nodes in the pool of miRNAs that interacted with the largest group of miRNAs for post-stroke at SI D4 and D27, respectively. KEGG pathway analysis showed 4 days of isolation resulted in the enrichment of pathways related to microglial activation and 27 days of isolation lead to the activation of neuronal-specific pathways that regulate cognition and motivation (FDR adjusted *p<0.05). At post-stroke SI D4, significant microglial activation was observed in independent validation cohorts as assessed by the median fluorescence intensity (MFI) of purinergic receptor P2Y12 (P2RY12), in CD45
int
CD11b
+
P2RY12
+
cells in the brain. MFI of P2RY12 was significantly downregulated in post-stroke SI mice at D4 (n=7-8/grp, *p<0.05) compared to PH mice.

Conclusions:
These findings validate our hypothesis that post-stroke SI exacerbates microglia activation and leads to differential expression of miRNAs involved in regulating microglial pathways. Taken together, utilizing miRNA-based therapies to restore miRNA-profiles in the brain may be able to alleviate the detrimental impact of post-stroke SI on chronic depressive-like phenotypes.
Abstract WMP23: Tobacco Cigarette Smoking Causes Cognitive Impairment Through Cerebrovascular Oxidative Damage
Authors: Ewees Mohamed , El-Mahdy Mohamed , Hannawi Yousef , Zweier Jay L
Published: February 2024

Introduction:
Tobacco cigarette smoking (TCS) has been established as a risk factor for cardiovascular disease. Recent epidemiological studies have identified an association between TCS and cognitive impairment. However, the underlying mechanisms are yet to be established. We hypothesize that chronic TCS induces systemic and cerebrovascular oxidative stress that leads to cognitive impairment.

Methods:
Male C57BL6 mice were exposed to cigarette smoke or air (two hours per day, five days per week) for up to 60 weeks, n =10/group. The vascular reactivity of the carotid artery (CA) was assessed using a wire myograph. The CA blood flow was measured by Doppler ultrasonography. Dihydroethidium and diaminofluorescein were used to measure superoxide and nitric oxide. Endothelial nitric oxide synthase (eNOS), tight junction proteins (occludin and caudine-5), β-amyloid, and phosphorylated Tau were measured by immunoblotting and immunofluorescence microscopy. We assessed the cognitive function using Barnes Maze and fear conditioning testing.

Results:
Vascular endothelial dysfunction occurred in the CA after 16 weeks of TCS exposure, followed by a 23% reduction in CA blood flow (P=0.0006). Superoxide was significantly elevated in the CA and subsequently in the brain of TCS-exposed mice by 181% (P<0.0001), compared to air-exposed mice. Reduction in eNOS and tight junction proteins were observed in the cerebrovascular endothelial cells. At 60 weeks of exposure, the brain of TCS-exposed mice showed higher levels of β-amyloid and phosphorylated-tau (352% and 260%, P=0.0032 and P<0.0001, respectively), compared to air-exposed mice. At this time, TCS-exposed mice exhibited impaired spatial learning and memory.

Conclusions:
TCS causes progressive systemic and cerebrovascular oxidative damage, leading to cognitive impairment. Targeting vascular oxidative stress is a potential strategy to mitigate cognitive function impairment.
Abstract WMP25: Implementing a Rapid Response Model to Improve Efficiency of In-Hospital Stroke Code Processes
Authors: Couts Linda , Libby Jill
Published: February 2024

Introduction:
In-hospital stroke (IHS), which occurs during hospitalization for other conditions, presents unique challenges and complexities. Studies have shown IHS is associated with worse patient outcomes, e.g., higher morbidity and mortality, compared to community-onset stroke treated in the emergency department. Time from initial symptom recognition to diagnostic imaging is critical for implementing first line therapy. During IHS, efficient and consistent performance of time-sensitive treatments relies on well-defined roles and parallel processing of tasks.

Method:
A QI initiative aimed at reducing time from initial stroke symptom recognition to initiation of a non-contrast CT (NCCT) scan was implemented at the start of FY 2022 at our CSC. Focus included broad education of all hospital personnel and their defined role in IHS recognition and care. Program analysis included retrospective and prospective data collected from patients’ electronic health records (EHR) and daily EHR audits for comparison of pre- and post-implementation data (FY 2021 and FY 2022, respectively). Data collection included time of stroke code call (symptom recognition), time of NCCT, and compliance of turn-around-time (TAT) between data points, with a goal of
<
20 minutes.

Results:
An overall increase in the number of IHS code calls between FY 2021 and FY 2022 (n=82 vs. n=106, respectively) was appreciated, with an overall decrease in mean time from stroke recognition to NCCT (
M
=22 vs.
M
=18.3 minutes, respectively). Overall compliance of TAT between these two data points increased from 53% to 73% post QI implementation. Additionally, we experienced an improvement in IHS activation time to IV thrombolytics administration time with a median time of 64.5 minutes (FY 2021, n=8) to median time of 59 minutes (FY 2022).

Conclusion:
Implementing a system wide QI initiative for IHS with well-defined roles and expectations, and parallel processing of tasks can lead to early recognition and activation of IHS code calls. Improved symptom recognition, code activation, and coordinated response efforts improved time and compliance to initial imaging as well as time to thrombolytic administration in our patient population.
Abstract WMP27: Strategies to Mitigate Tenecteplase (TNK) Dosing Errors in Acute Ischemic Stroke
Authors: Meinhold Marlies , DiFranco Theresa , Hushen Patricia
Published: February 2024

Tenecteplase (TNK) is currently being used for IV thrombolysis in acute ischemic stroke. “Tenecteplase is the first thrombolytic that can be administered over five seconds in a single dose.” (Genetech, 2023). While this is a great advance for thromboembolic pathology, dosing errors can cause devastating patient harm including death. This off-label use can lead to dosing errors related to the TNK packaging, which only states dosing for myocardial infarction. The dosing for myocardial infarction is 0.5 mg/kg while the dosing for stroke is 0.25 mg/kg. (Bach, 2023; Campbell et al., 2018; Wang et al., 2023). While implementing TNK for acute ischemic stroke, discrepancies were also noted in the rounding of the TNK dose. Dosages were rounded to the onehundredth decimal point, and clear labeling on the package was not evident. The significance of underdosing or overdosing of TNK may not achieve the desired patient outcome and may increase the risk of complications such as hemorrhage, anaphylaxis, thromboembolism, arrhythmia, intracranial hemorrhage, extended hospitalizations, and death. (Bach, 2023) Education was created and disseminated to inform physicians and nursing of the appropriate dosing of TNK for acute ischemic stroke. A TNK dosing chart was included with the pre-existing stroke packets to reinforce learning. The TNK dosing chart was updated to round the TNK dose to the nearest tenth of a decimal, then one step further with the chart showing the dosage to weight ranges. Interdisciplinary collaboration occurred with informatics, physicians, pharmacy, and nursing to get order sets to match the rounding rules. Lastly, special labeling was created for the packaging of Tenecteplase TNK to include dosing for acute ischemic stroke. Since the implementation of this quality improvement project, both nursing and physicians are more aware of the correct dosing of TNK for acute ischemic stroke and myocardial infarction. Mitigating the problem of unclear TNK dosing has prevented dosing errors for acute ischemic stroke and myocardial infarction as well as the negative outcomes associated with a medication error involving a high-alert medication.
Abstract WMP35: What's Your Time Worth?: Improving Efficiency in Tracking Core Measures Compliance in Real Time
Authors: Stein Laura A , Pomeroy Jon , Spahr Melissa , Scavicchio Karlie , Rothstein Aaron , Tambe Ujwala , Blum Christina , Cristancho Daniel , Yellareddigari Megan , Owens Karrima , Sellers Michele , Hoey Colin
Published: February 2024

Background:
Stroke program development and expansion requires excellent patient care and continued quality improvement via ongoing data collection. Substantial time and effort are required to identify patient records and manually assess metrics within charts. While real-time assessment of this data is ideal, achieving this is challenging.

Purpose:
We sought to create a real-time, electronic medical record (EMR) derived patient tracking list to improve accuracy, efficiency, and timeliness of stroke patient data collection.

Methods:
Ischemic stroke patient identification was optimized utilizing current patient lists, which over capture, and applying filters based on EMR entries applicable to stroke patients. Patient capture was reviewed to ensure adequate sensitivity and specificity. Subsequently, key stroke quality data points were identified. Custom columns were created to pull data from across the EMR into a central list. Column data was validated to ensure accuracy and confirm improved efficiency via timed chart reviews. A Mann-Whitney test was used to compare means pre and post-review. Of note, different reviewers performed pre and post reviews.

Results:
A stroke tracking list was successfully implemented. Chart review in the previous process averaged 173.2 seconds (STD 40.6) vs. 121.3 seconds (STD 17.8) in the new process (p<0.05). Patient identification times were not compared, though identifying charts in the old workflow ranged from 12 to 15 minutes per chart.

Conclusions:
Creation of a central tracking list within the electronic medical record is feasible and can improve patient identification, coordination of critical data sharing, and data collection efficiency. Utilization decreased data collection times and prompted creation of similar tracking lists for other core measure data. While sample sizes were small and pre and post reviewers were different, this work demonstrates feasibility and early foundational work.
Abstract WMP36: Quality Improvement for Improved Ischemic Stroke Large Vessel Occlusion Door-In-Door-Out Times at an Urban Primary Stroke Center Integrated Health System
Authors: Kruze Kelley P , Zrelak Patricia A , Betjemann John P
Published: February 2024

Background:
Stroke patients who present to an Emergency Department (ED) with an acute ischemic stroke (AIS) due to a large vessel occlusion (LVO) and are eligible for endovascular stroke therapy (EST) require rapid transfer to a facility capable of EST. Nationwide data for 2022 suggest that 19% of LVO patients are transferred for EST within 90 minutes. Our practice center is a large urban community-based Primary Stroke Center, part of a spoke and hub integrated system. In 2022, we had a median door-in-door-out (DIDO) time of 98 min with 33% percent of cases under 90 min (n = 12).

Purpose:
Knowing the importance of early reperfusion, we implemented a quality improvement project using a pre-post design to improve our DIDO times for patients with AIS due to LVO, with a goal of achieving a median DIDO time of 75 min or less.

Methods:
Our approach was multidisciplinary. We completed comprehensive chart reviews focusing on critical time points and reviewed recent literature (2022 - 2023) for best practices. We created an ED interdisciplinary DIDO workgroup which developed and implemented a DIDO checklist after education and socialization. In March 2023, we created a dedicated regional neuro transfer hub to address changes with EMS notification and response to expedite LVO transfers. Other DIDO literature recommendations were already in place, including the use of a regionalized telestroke program. Best practices identified but not implemented focused on Emergency Medical Services (EMS), such as holding a rig while completing imaging, providing enroute reports, and conducting joint drills post-COVID.

Results:
After the implementation of the DIDO checklist, DIDO times decreased to 82 minutes from August 2022 to July 2023 (a decrease of 16 min), with 44% of cases under 75 mins (n = 9). Our median time for 2023 (January - July) is 68 min (n = 2).

Conclusion:
Transfer of LVO patients is a low-volume, high-risk event, but one where every minute matters for optimal patient outcomes. The DIDO checklist was a helpful aid for staff to ensure key steps were completed timely, leading to a decrease in DIDO times.
Abstract WMP48: The Brain Emergency Management Initiative: Reduction of Embolectomy Transfer Times Using a Novel Telestroke Transfer Protocol
Authors: Wood Carla N , Meyer Dawn M , Shifflet Benjamin , Modir Royya F , Hansra Harjot , Davila Claire , Bu Julia , Meyer Brett C , Bavarsad Reza
Published: February 2024

Recent studies of national door-in-door-out times (DIDO) in the Get with the Guidelines Stroke registry found that <30% of transfers for acute interventions were completed within the recommended 120 minute timeframe. There is a critical need for effective emergent transfer protocols to improve outcomes. The Brain Emergency Management Initiative (BEMI) is a telestroke transfer protocol connecting acute stroke patients at hub sites to a spoke center for embolectomy. BEMI includes early activation of helicopter transport, rapid imaging transmission, standardized documentation, and remote patient admission. BEMI has been shown to significantly reduce DIDO and time-of-treatment-decision-to-groin-puncture (TDGP). The aim of this study was to evaluate the sustainability of the BEMI impact on reduction of key transfer metrics. We retrospectively assessed prospectively collected data for patients transferred for embolectomy in our telestroke system. Patients were assessed in 3 groups: pre-BEMI (2013-mid 2016; before protocol, n=32), early-BEMI (mid 2016-2017; initial year of protocol, n=31) and new-BEMI (2018-2023; n=210). Inclusion criteria were emergency telestroke consultation and transfer for acute embolectomy. Exclusion criteria were inpatient telestroke consultation, incomplete data and aborted transfers. Variables were assessed via Chi-square, T-test or Wilcoxon Rank Sum as appropriate. Median times were used given skewedness of data. We evaluated 273 total transfers. Analyses compared BEMI groups to the pre-BEMI group. Median NIHSS was higher in the BEMI groups (pre-BEMI median=10 points vs. early-BEMI=20,
p=0.0063
; vs. new-BEMI=17,
p=0.005
). There were significantly shorter median DIDO and TDGP times in the BEMI groups (DIDO: pre-BEMI median=143 minutes vs. early-BEMI=118,
p=0.015
; vs. new-BEMI=97,
p=1.7e-7
) (TDGP pre-BEMI median=155 minutes vs. early-BEMI=130,
p=0.01
; vs. new-BEMI=125,
p=6.8e-14
). This finding was sustainable from the early to new BEMI groups. Additional time metrics will be assessed in this dataset. The BEMI protocol significantly improved transfer and treatment times in our telestroke network. BEMI may serve as a model for stroke transfer protocols at other centers to assist in improving time metrics.
Abstract WMP5: Intravenous Thrombolysis Before Thrombectomy Improves Functional Outcome After Stroke Independent of Reperfusion Grade
Authors: Sedghi Annahita , Kaiser Daniel , Cuberi Ani , Schreckenbauer Sonja , Wojciechowski Claudia , Friehs Ingeborg , Reichmann Heinz , Barlinn Jessica , Barlinn Kristian , Puetz Volker , Siepmann Timo
Published: February 2024

Background:
We studied the effect of intravenous thrombolysis (IVT) before thrombectomy for anterior circulation large vessel occlusion (acLVO) on functional outcome and scrutinized its dependence on grade of reperfusion and distal thrombus migration.

Methods:
We included consecutive acLVO patients from our prospective registry of thrombectomy-eligible patients treated from 01/01/2017 to 01/01/2023 at a tertiary stroke center in Germany into a retrospective cohort study. We evaluated the effects of IVT on functional outcome quantified via modified Rankin scale (mRS) at 90 days applying multivariable logistic and lasso regression including interaction terms with grade of reperfusion quantified via modified Thrombolysis in Cerebral Infarction (mTICI) scale and distal thrombus migration adjusted for demographic and cardiovascular risk profiles, clinical and imaging stroke characteristics and onset-to-recanalization time. We performed sensitivity analysis using propensity score matching.

Results:
In our study population of 1000 thrombectomy-eligible patients (513 females, median age 77 [67-84, interquartile range]) IVT emerged as predictor of favorable functional outcome (mRS 0-2) independent of mTICI (adjusted OR 0.49; 95% CI [0.32;0.75]; p=0.001). In those who underwent thrombectomy (n=812) the association of IVT and favorable functional outcome was reproduced (adjusted OR 0.49; 95% CI [0.31;0.74]; p=0.001) and was further confirmed on propensity score analysis where IVT led to a 0.35-point decrease in 90-day mRS score [ß=-0.35; 95CI% [-0.68;-0.01]; p=0.04]. The additive benefit of IVT remained independent of mTICI (ß=-1.79; 95% CI [-3.43;-0.15]; p=0.03) and distal thrombus migration (ß=-0.41; 95% CI [-0.69;-0.13]; p=0.004) on interaction analysis. Consequently, IVT showed an additive effect on functional outcome in the subpopulation of thrombectomy patients who achieved successful reperfusion (TICI≥2b; ß=-0.46; 95% CI [-0.74;-0.17]; p=0.002) and remained beneficial in those with unsuccessful reperfusion (TICI≤2a; ß=-0.47; 95% CI [-0.96;-0.01]; p=0.05).

Conclusions:
In thrombectomy-eligible acLVO patients IVT improves functional outcome independent of grade of reperfusion and distal thrombus migration.
Abstract WMP52: Demographic Trends in Stroke-Related Mortality in Young Adults (Age:15-55 Year) With Concomitant Opioid Use in the United States From 1999-2020
Authors: Sohaib Muhammad , Chaychi Muhammad T , Mannan Muhammad S , Shafiq Talha , Kamal Haris , Ahmed Muhammad K
Published: February 2024

Background:
The estimated range for the prevalence of Opioid Use Disorder (OUD) among adolescents and adults in the United States in 2019 was between 6.7 million and 7.6 million individuals. The overall mortality rate is increasing over the last 20 years.

Objective:
This study aimed to assess the trends in stroke-related mortality in chronic opioid users in different demographics in the United States.

Methods:
We analyzed Center for Disease Control and Prevention Wide-Ranging On-Line Data for the Epidemiologic Research database examined from 1999 to 2020 for multiple causes of death MCD-ICD 10 Codes. Stroke-related mortality rates, with and without opioid use, were stratified by age, sex, and race/ethnicity and expressed as age-adjusted mortality rates (AAMRs) per 100,000 persons. Annual percent change (APC) from 1999-2020 was calculated and graphically plotted.

Results:
Between 1999 and 2020, The were 307,615 stroke-related deaths and 358,322 opioid-related deaths occurred among adults (15-55), and 1615 deaths were related to stroke and opioid use. The age-adjusted mortality rate (AAMR) steadily increased from 0.1 in 1999 to 0.8 in 2020, with an annual percent change (APC):9.6 % (CI: 8.0-12.14). Men and women had unreliable differences from 1999 till 2011. Men had consistently higher AAMR than women from 2011 (AAMR men: 0.4 vs. women: 0.2; p:<0.005) to 2020 (AAMR men: 1.1 vs. women: 0.5 p:<0.006). Non-Hispanic (NH) Black or African American adults had the highest overall AAMR (0.5), followed by NH White (0.4), followed by Hispanic or Latino (0.3).

Conclusion:
There has been a steady increase in opioid-related Stroke mortality in the U.S. among adults 15-55 years with opioid use from 1999-2020. African American adults and men possessed the highest age-adjusted mortality rates (AAMRs) related to stroke with concomitant opioid use. Young adults require targeted stroke prevention and management strategies to reduce stroke-related mortality in the presence of concomitant opioid use.
Abstract WMP54: Detection of Late Complications After Stroke in Younger versus Older Adults With Ischemic Stroke Using Active Surveillance versus Usual Care: A Retrospective Cohort Study
Authors: Lan Bo , Corlin Laura , Skeels Katelyn , Lynch Grace , Tan Sandy , Melkumova Emiliya , Leung Lester
Published: February 2024

Introduction:
Late complications after stroke (LCAS) impede return to pre-stroke responsibilities and worsen quality of life, yet they can be readily treated. We previously demonstrated that an active surveillance approach could improve LCAS detection in young adults. However, it is not known if a similar strategy would be useful for older adults. We assessed differences in LCAS detection and resultant clinical practice changes (CPC) among young and older stroke survivors using both active surveillance and usual care approaches.

Methods:
We retrospectively collected data from the EHR at Tufts Medical Center for patients age ≥ 18 with acute ischemic stroke (AIS) and Stroke Clinic evaluations including demographics, comorbidities, presence of LCAS (including central pain, cognitive impairment, dystonia, headache, insomnia, lethargy, mood disorders, orthostasis, seizures, and spasticity), and evidence of CPC (diagnostic test, prescription, or referral). Differences in LCAS detection and in clinical practice change between age groups were compared during three-time intervals (0-3 months, 3-12 months, 0-12 months), and stratified by surveillance strategy. Descriptive statistics and multivariable logistic regression were used to identify predictors of LCAS detection and CPC.

Results:
Three hundred eleven AIS survivors (16% young, 44% female, 42% non-white) were included, with 43% undergoing active surveillance. Older adults were more likely to have a non-English preferred language. While LCAS were detected more frequently in young adults (86% vs 65%, p=0.003), the overall proportion was high in both age groups. Motor LCAS were detected at similar proportions (20% vs 12%, p=0.15), but nonmotor LCAS were detected more in young adults (91% vs 71%, p=0.003). Among all AIS survivors, active surveillance was associated with higher proportion of LCAS detection for nonmotor symptoms but not for motor symptoms. In analyses adjusted for surveillance method and age, active surveillance was strongly associated with any LCAS detection and with CPC for any LCAS and nonmotor LCAS.

Conclusions:
Active surveillance increases LCAS detection in both young and older AIS survivors compared to usual care, and it is a major determinant of CPC for nonmotor LCAS.
Abstract WMP6: Dual Antiplatelet Therapy versus Alteplase in Patients With Minor Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Dagostin Caroline , Sales de Oliveira Jéssica , Udoma Udofa Ofonime Chantal , Martins Otávio , Navalha Denilsa , Neves Faria Fernandes Mateus , Medeiros Dantas Julyana , Pereira Muniz Pontes Julia , Cotrim Gomes Fernando , Borges Nager Gabriela , Laura Lima Larcipretti Anna , de Andrade Bannach Matheus
Published: February 2024

Background:
Minor stroke, defined as a National Institutes of Health Stroke Scale (NIHSS), score of less than or equal to 5, accountedfor half of Acute Ischemic Stroke (AIS) patients in 2019 . Given the low impairment on function, there is a debate about which therapy is better for these patients: intravenous alteplase or double antiplatelet therapy (DAPT).Research question: For patients with minor AIS who can be treated within 24 hours after symptom onset, is alteplase associated with better outcomes and a good safety profile?

Methods:
We systematically searched PubMed, Web of Science, and EMBASE. Outcomes of interest included: Modified Rankin Scale (mRS) 0-1, symptomatic intracranial hemorrhage (sICH) and stroke recurrence. Heterogeneity was examined with I2 statistics, and a random-effects model was used for all of the outcomes due to expected high heterogeneity.

Results:
We included 1 randomized controlled trial and 3 observational cohorts, comprising 2,224 patients. DAPT was administered to 1,395 (62.7%) patients. DAPT was associated with a significantly lower incidence of sICH (OR 0.21; 95% CI 0.05-0.83; P=0.03; Fig 1A). There was no significant difference between DAPT and alteplase in good clinical outcome (mRS 0-1) at 90 days (OR 1.19; 95% CI 0.67-2.11; P=0.55; Fig 1B) or stroke recurrence (OR 0.87; 95% CI 0.51-1.48; P=0.61; Fig 1C).

Conclusion:
In this systematic review and meta-analysis comparing alteplase and DAPT in patients with minor non-disabling acute stroke, DAPT was associated with lower risk of sICH and there was nodifference in excellent clinical outcome or stroke recurrence at 90 days.
Abstract WMP60: Comparison of Demographic and Clinical Characteristics and the CDC Social Vulnerability Index Among Medicare Beneficiaries Hospitalized With Acute Ischemic Stroke, April 2020 - December 2021
Authors: Tong Xin , Kuklina Elena V , Merritt Robert K
Published: February 2024

Introduction:
Extensive evidence shows that social inequities create health disparities. However, limited information exists on how demographic and clinical factors are associated with social inequities among older patients hospitalized with acute ischemic stroke (AIS) during COVID-19.

Methods:
We analyzed data on Medicare fee-for-service beneficiaries aged ≥65 years hospitalized with AIS from April 1, 2020, to December 31, 2021. All patients were followed until March 31, 2023. We used US Centers for Disease Control and Prevention’s 2020 Social Vulnerability Index (SVI) and compared demographic and clinical features by SVI tertiles (low 0-0.33, moderate 0.34-0.66, high 0.67-1.0).

Results:
Among 249299 Medicare FFS beneficiaries with AIS, there were 57814 (23.2%) with low, 88565 (35.5%) moderate, and 102920 (41.3%) high SVI. Demographic and clinical features differed significantly across SVI tertiles. Compared to AIS patients living in low SVI communities, patients living in high SVI areas were significantly younger (median age 79.0 vs 79.9 years), more likely to be non-Hispanic Black (15.4% vs 4.3%), had more severe stroke at admission per National Institutes of Health Stroke Scale (NIHSS) score (9.4% NIHSS ≥20 vs 8.4%), more history of COVID-19 (7.7% vs 6.3%), higher proportion of death at the end of follow-up (40.4% vs 38.2%), and more comorbidities.

Conclusion:
Medicare patients with AIS hospitalizations live in communities with higher SVI. These data identified racial disparities and more severe outcomes among AIS patients living in areas with higher social vulnerabilities, signaling a need for multisectoral interventions and policies that impact AIS outcomes.
Abstract WMP63: Oxygen Metabolic Stress Attributes Intrinsic Vulnerability to Watershed Regions in Healthy Individuals
Authors: Das Saurav , Kang Peter , Chen Yasheng , Dong Junling , Kiguradze Tina , Ying Chunwei , Hooper Destiny , Ford Andria L , An Hongyu , Chatterjee Arindam R , Lee Jin Moo
Published: February 2024

Introduction:
Physiological imaging studies in patients with severe steno-occlusive carotid disease (SSCD) reveal hemodynamic compromise as a mechanism underlying watershed infarcts (WI). However, it is unclear if the watershed region (WR) is intrinsically vulnerable in healthy individuals. We measured cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in healthy individuals to determine if the WR was under metabolic stress, and therefore an intrinsically vulnerable region.

Methods:
To define a common WR, we created an “average WI density map” using MRIs from patients with diffusion restriction ipsilateral to SSCD from a single academic center (7/10 to 8/20). WI density maps were created using 5%, 10% and 15% incidence thresholds. Maps were overlaid onto coregistered CBF and OEF maps generated from pseudo-continuous arterial spin labeling (pCASL) and asymmetric spin echo sequences, respectively, performed on healthy controls aged <55 with no vascular risk factors. OEF was normalized to whole brain values. White matter OEF and CBF was compared within vs. outside the WR using the Kruskal Wallis test.

Results:
47 MRIs (mean age 62 years, 55 % females) were used to create average WI density maps using 3 thresholds (Fig A). Average CBF and OEF maps were created from 29 healthy volunteers (mean age 39 years, 59 % females). WI maps were superimposed on the CBF and OEF maps from healthy controls. OEF was higher (p<0.001), and CBF lower (p<0.001) within compared to outside the watershed regions, regardless of incidence threshold used (10% threshold shown in Fig. B-C).

Conclusion:
Increased OEF and decreased CBF suggest oxygen metabolic stress in the WR, suggesting that the deep white matter may be intrinsically vulnerable even in healthy individuals. Indeed, several brain pathologies (WI, white matter hyperintensities of presumed vascular origin, and multiple sclerosis lesions) are known to fall within this region.
Abstract WMP64: Late Lesion Growth Following Endovascular Therapy: Is 24 Hours Too Early to Assess Acute Infarct Size Including the Effects of Secondary Injury?
Authors: Luby Marie , Hsia Amie W , Lomahan Carolyn A , Uche Victoria , Davis Rachel , Kim Yongwoo , Somani Sana , Burton Shannon , Cabatbat Rainier Michael , Craft Veronica , De Vis Jill , Adil Malik , Afzal Mariam , Thomas Leila , Gandler William , McCreedy Evan , Lynch John K , Latour Lawrence
Published: February 2024

Background:
Measurement of “final” lesion volume at 24hr following endovascular therapy (post-EVT) has been used in multiple studies as a surrogate for clinical outcome. However, despite successful recanalization, a significant proportion of patients do not experience favorable clinical outcome.

Methods:
This is a prospective study of acute ischemic stroke patients at two stroke centers who met the following criteria: i) anterior large vessel occlusion (LVO) acute ischemic stroke, ii) attempted EVT, iii) written informed consent obtained, and iv) had MRI post-EVT at 24hr and 5-day. We defined “Early” and “Late” lesion growth as ≥10mL lesion growth between baseline and 24hr DWI, and between 24hr DWI and 5-day FLAIR, respectively.

Results:
One hundred fourteen patients met study criteria with median age 67 years, 56% female, median admit NIHSS 19, 54% received IV or IA thrombolysis, 67% with M1 occlusion, and median baseline DWI volume 28.2mL. Successful recanalization was achieved in 86% and 67% had complete reperfusion, with an overall favorable clinical outcome rate of 54%. Nearly two thirds (65%) of the patients did not have Late lesion growth with a median volume change of -0.2mL between 24hr and 5-days and an associated high rate of favorable clinical outcome (65%). However, ~1/3 of patients (35%) did have significant Late lesion growth despite successful recanalization (85% TICI 2b/3). Late lesion growth patients had a 26.2mL change in Late lesion volume and 19.9mL change in Early lesion volume. These patients had an increased hemorrhagic transformation rate of 68% with only 1 in 3 patients having favorable clinical outcome. Late lesion growth was independently associated with incomplete reperfusion, hemorrhagic transformation, and unfavorable outcome even after adjusting for admit NIHSS and Early lesion growth.

Conclusions:
Approximately 1 out of 3 patients had Late lesion growth following EVT, with a favorable clinical outcome occurring in only 1 out of 3 of these patients. Identification of patients with Late lesion growth could be critical to guide clinical management and inform prognosis post-EVT. Additionally it can serve as an imaging biomarker for the development of adjunctive therapies to mitigate reperfusion injury.
Abstract WMP69: Brain Atrophy and White Matter Disease Agreement on NCCT and MRI in Ischemic Stroke
Authors: Betzner William , Singh Nishita , Alhabli Ibrahim , Bala Fouzi , Benali Faysal , Lam Kaden , Almekhlafi Mohammed A , Buck Brian H , Catanese Luciana , Sajobi Tolulope , Tkach Aleksander , Menon Bijoy K , Swartz Richard H , Ganesh Aravind
Published: February 2024

Background:
NCCT is the most widely used parenchymal imaging for acute stroke. Evaluations of brain frailty measures like atrophy and white matter disease (WMD) are becoming increasingly relevant in stroke outcome prediction but are conventionally thought to be best seen on MRI. We assessed the agreement between baseline NCCT and follow-up MRI ratings of brain atrophy and WMD and compared their predictive validity in relation to 90-day functional outcomes in acute ischemic stroke.

Methods:
In this post-hoc analysis of baseline NCCT and follow-up MRI data from the Alteplase compared to Tenecteplase (AcT) randomised-controlled trial, expert readers (stroke neurologists and radiologists) assessed atrophy using the global cortical atrophy (GCA), Koedam, and medial temporal lobe atrophy scales. WMD was measured using the Fazekas scale. Binary agreement (none-mild vs. moderate-severe) and agreement across the full range of scores between atrophy and WMD measures on NCCT and MRI were calculated using Gwet’s agreement coefficient (AC1). Logistic regressions and Delong’s test were used to compare the area under the curve (AUC) for the prediction of 90-day modified Rankin score (mRS) 0-1 when using NCCT vs MRI-based ratings for each atrophy and WMD variable.

Results:
Of 1577 patients included in the AcT trial, 491 had interpretable NCCT+MRI. Binary agreement was substantial (AC1:0.68-0.80) for deep and total WMD scores, Koedam scale and frontal GCA. Almost perfect binary agreement (AC1:0.81-0.97) was found for all other measures. Deep white matter showed a significant difference between NCCT and MRI ratings for predicting 90-day mRS 0-1 (MRI AUC = 0.61 [0.56-0.66], CT AUC = 0.56 [0.50-0.60], p = 0.01, Delong p = 0.02) There was no significant difference in predicting 90-day mRS for the other variables (all p > 0.12, GCA: MRI AUC = 0.54 [0.49-0.60] CT AUC = 0.53 [0.47-0.58], p = 0.58, Delong p = 0.86).

Conclusion:
NCCT ratings of brain atrophy and WMD by experts have substantial to almost-perfect agreement with MRI atrophy and WMD ratings and achieve similar prediction of 90-day mRS 0-1 functional outcomes in acute stroke patients. This implies that it is reasonable to use NCCT scans to evaluate these brain frailty measures in clinical practice and in stroke trials.
Abstract WMP7: Impact of Telestroke Access in a Rural Setting
Authors: Adcock Amelia , Sarvath Mohammed , D'Andrea Nina , Marku Vjosa , Seachrist Eric , Petrone Ashley
Published: February 2024

Background:
Despite decades long adoption as the standard-of-care for ischemic stroke, the majority of eligible patients do not receive intravenous thrombolysis (IVT), with underutilization especially pronounced in rural areas. Telestroke, however, may help alleviate this geographical healthcare disparity. The current study aims to identify the impact of implementing a mature telestroke network within a rural setting.

Methods:
Retrospective review of a prospectively maintained telestroke database from a large rural tertiary care comprehensive stroke center covering 31 spoke hospitals spanning critical access hospitals to primary stroke centers between 10/2021-02/2023. Data was compared to a previous review period (01/2016-12/2018; comprised of 8 spokes) and the statewide IVT rates recorded in GWTG. Data analysis conducted via descriptive statistics and Fisher’s (two-tailed) exact test.

Results:
1801 telestroke consults were performed; 41.4% (746/1801) were ineligible for acute stroke intervention. 39% (410/1055) of eligible patients were treated with IVT (vs. 33% [317/959] previously, p = 0.068), representing 58% (410/708; vs 24% [107/448] previously, p < 0.001) of statewide total IVT administration. Symptomatic hemorrhage (sICH) was 3.0%, overall 30-day mortality was 5.6%, and sICH mortality was 1.0%. IVT deferred most commonly: low NIH (44%), mimics (21%), coagulopathy (8%), followed by other. 22% (396/1801) of total consults were transferred from the originating site (vs. 34% [305/890] previously, p < 0.0001) of which 10% (42/396) underwent EVT.

Discussion:
The impact of expanding a rural telestroke network continued to produce high IVT rates (nearly double the national average) with safety outcomes (sICH, mortality) at or below national standards. Additionally, a large network has significantly increased the proportion of patients remaining at originating sites, optimizing both tertiary and local centers’ resources. The value of a regional telestroke hub is further underscored by the significant increase in statewide IVT attributed to network consults. However, further strategies are needed to better educate rural providers on acute stroke to reduce the rate of ineligible consults and streamline use of telestroke services.
Abstract WMP70: Neuroradiological Markers of Cerebral Small Vessel Disease in Adults With Congenital Heart Disease After Fontan Surgery
Authors: Sariyeva Mehriban , Kochav Jonathan , Mammadli Gular , Haghighi Noora , Argenio Melissa , Bilski Amanda , Gutierrez Jose , Ibeh Chinwe , Willey Joshua Z , Rosenbaum Marlon , Lewis Matthew , Miller Eliza C
Published: February 2024

Introduction:
Fontan surgery performed during childhood enhances the lifespan and quality of life of patients with critical congenital heart disease. Post-Fontan circulation may impact function in multiple organ systems, but its long term effects on the brain microvasculature are not well characterized. We investigated brain MRI markers of cerebral small vessel disease (SVD) after exposure to Fontan circulation.

Methods:
We reviewed medical records and MRI images of 34 adults followed in an academic medical center after Fontan surgery, who had brain MRI for any reason from 08/01/1995-03/01/2022. We characterized Fontan physiological stage (a standardized measure of disease severity) at time of MRI, and identified SVD markers, including deep silent brain infarcts, small perivascular spaces in the basal ganglia, microhemorrhages, and white matter hyperintensities. We calculated SVD scores using a standardized scale of 0-4, where scores of ≥2 indicate moderate to severe SVD. We created ordinal logistic regression models to test the association between physiological stage and SVD score.

Results:
Characteristics of the patients are summarized in the Table, and distribution of SVD scores in the Figure. Adjusting for age at MRI, there was no association between physiological stage of disease and higher SVD score.

Conclusion:
In our sample of 34 young adult patients with long term exposure to Fontan circulation, the majority had evidence of moderate to severe SVD, which was not predicted by physiological stage of disease at time of MRI. Exposure to Fontan circulation may be associated with early onset of cerebral SVD, suggesting increased long term risk of stroke and dementia.
Abstract WMP74: Inhibition of T Cell Receptor Activation Improves Neurological Outcomes After Intracerebral Hemorrhage
Authors: Xiu Yuwen , Wang Yingjie , Shi Mengxuan , Zhou Di , Kilgore Mitch , Shi Samuel X , Liu Ning , Jiang Yinghua , Dumont Aaron S , Wang Xiaoying
Published: February 2024

Purpose:
We previously reported that activated T cells accumulate in the perihematomal regions after Intracerebral hemorrhage (ICH) and aggravate hemorrhagic brain injury. However, brain-infiltrating T cells precise activation mechanisms and resulting pathological impacts remain largely unexplored. This study aims to address these knowledge gaps.

Methodology:
ICH was induced via standard collagenase injection in male C57BL/6J mice (10 weeks old). Activation pathways of T cells were analyzed through single-cell RNA data (GSE230414). We assessed T cell receptor (TCR) activation, pro-inflammatory cytokines expression, and immune cell infiltration via flow cytometry and immunostaining at 1- and 3-days post-ICH. Neurobehavioral evaluations were conducted at 1-, 3-, 7-, and 14-days post-ICH. TCR activation was pharmacologically inhibited using the TCR-specific inhibitor AX-024, administered (10 mg/kg, i.p.) one hour after ICH.

Results:
Single-cell transcriptomic analysis revealed an upregulation of the TCR pathway in activated T cells following ICH in mice. Flow cytometry and immunostaining validated TCR activation markers (p-CD3, p-Zap70) in ICH mouse models. These findings suggest that TCR activation likely plays a central role in the activation of brain-infiltrating T cells. In the subsequent experiment, we explored the pathological implications of TCR activation on T cell activation, leukocyte brain infiltration, and neurological outcomes post-ICH. We found that administration of AX-024 substantially inhibited TCR activation (CD69 expression) and expression of pro-inflammatory cytokines (IL-17, IL-1β) in brain-infiltrating T cells at 1- and 3-days post-ICH. Notably, AX-024 administration also significantly decreased the infiltration of other leukocytes and remarkably enhanced long-term sensorimotor and cognitive function up to 14 days after ICH.

Discussion:
This study underscores TCR activation as a pivotal mechanism driving activation of brain-infiltrating T cells following ICH. Inhibiting TCR activation through AX-024 proves beneficial for improving neurological outcomes after ICH. However, further investigations are warranted to comprehensively elucidate the intricate underlying pathological mechanisms.
Abstract WMP75: Neurobehavioral Outcomes Following Left- and Right-Sided Intracerebral Hemorrhage in Mice
Authors: Cooper Dawson , Abramson Efrat , Sansing Lauren H
Published: February 2024

Background:
Injury location is an established outcome predictor in intracerebral hemorrhage (ICH), with most studies focusing on outcomes relating to motor deficits. However, location may also affect other neurobehavioral deficits following ICH, such as mood and cognitive decline. To address this gap, we studied neurobehavioral outcomes following left and right-sided ICH in mice.

Methods:
Three-month-old male mice (C57BL/6) were given a left (n=5) or right-sided (n=5) ICH. In short, type VII collagenase was injected into the left or right striatum (0.0 mm anterior, +/- 2.3 mm lateral, and 3.6 mm deep from bregma). Naïve mice (n=5) were used as controls. Behavior was assessed at day 28 post-ICH using a video-recorded three-chamber sociability task in which one chamber had an enclosed male stranger mouse. Distance traveled, time in each chamber, and time exploring the stranger mouse were quantified using automated software (AnyMaze). Data were analyzed by one-way ANOVA and Tukey post-hoc tests.

Results:
ICH location had differential effects on behavioral outcomes. Compared to naïve and right-sided ICH mice, left-sided ICH mice traveled a greater overall distance exploring the chambers (both p<0.05), spent a greater overall time immobile in the stranger mouse zone (both p<0.001) and less time oriented towards the stranger mouse (both p<0.05). Furthermore, when comparing naive and left-sided ICH mice, left-sided mice had a higher frequency of investigations of the empty cage (p<0.05). No significant differences were found between the naïve and right-sided ICH mice.

Conclusions:
These results reveal differences in behavioral phenotypes associated with left- and right-sided ICH.