bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP243: Telestroke or Face-to-Face Assessment for Unmask Stroke Mimic
Authors: Cardona Pedro , Nuñez Guillen Anna , Lara Blanca , Quesada Helena , Paipa Andres , Bernal Teresa , Franquet Elsa , Catena Ester , Escrig Anna
Published: June 2021

Background:
Stroke mimic (SM) is a common diagnosis in stroke assessment in our medical emergency systems. The diagnosis of SM requires an expertise neurological exam and probably support it by radiological tests. Different frequency of SM could be reported according to different epidemiological or clinical values. The rate of stroke mimic could be different between primary telestroke exam and face-to-face evaluation in comprehensive stroke center, and also chameleon syndromes (false SM) could present differences in percentage of diagnosis.

Methods:
A total of 3876 stroke codes were evaluated by our team of vascular neurologist in our comprehensive stroke center (CSC) and 415 patients were evaluated by telestroke with our referenced county hospitals between January 2014 to March 2019. We analyzed the percentage of SM in this period in both types of assessment: face-to-face or telemedicine. We analyze if there are any differences in percentage of SM diagnosis, frequency of SM subtypes or delay in diagnosis according to the evaluation method.

Results:
The percentage of SM diagnosis was 12% in our CSC and 11.1% by telemedicine assessment. Patients with SM were significantly younger than radiological confirmed stroke (63 vs 74 years; p:0.001) and had lower NIHSS (7 vs 9; p:0.003). We found significant differences between age and main subtypes of SM (conversion, brain tumor, confusional disorders). However they didn’t present any significant differences according to evaluation method (face-to-face in CSC or telestroke). Besides, there was difference in percentage of chameleon syndrome (3,2% and 2,2% respectively) but it was no significant.

Conclusions:
The percentage of SM diagnosis by vascular neurologist is similar with independence of method of evaluation: on-site or telemedicine. However the percentage of chameleon syndrome could be lower by telestroke assessment.
Abstract TP246: Refining Hyperacute MRI Protocols to Increase Patient Eligibility for IV tPA
Authors: Shehabeldin Mohamed , Farkas Nathan S. , Giles James A. , Eldaya Rami , Goyal Manu , Heitsch Laura , Panagos Peter , Ford Andria L.
Published: June 2021

Introduction:
Hyperacute MRI (hMRI) increases the number of patients eligible for IV tPA in: (1) patients initially suspected to be stroke mimics (SM) and (2) patients with wake-up or unwitnessed stroke onset (WU-UW). Performing hMRI in a time-frame to enable tPA delivery is challenging for many centers; thus, we evaluated which factors were associated with delays in hMRI and hMRI-related tPA treatment at our institution since publication of the WAKE-UP stroke trial in August 2018.

Methods:
We analyzed 1-year of prospectively collected hMRI data performed between 07.01.2018 to 06.30.2019. We divided the year into three 4-month epochs; the 1
st
epoch was before and the 2
nd
and 3
rd
epochs were after implementing the Wake-up protocol for WU-UW stroke presentations as a new indication to our streamlined hMRI protocol. We compared baseline variables, hMRI indication, hMRI-related tPA utilization, and time metrics for completing hMRI between the 2
nd
and 3
rd
epochs. We also evaluated discharge outcomes and safety of tPA treatment in this hMRI cohort.

Results:
Across the 3 epochs, 84 patients underwent hMRI (n=10 vs. 37 vs. 37, respectively), of whom 13 were treated with IV tPA. hMRI-related tPA utilization increased in epochs 2 vs 3 after initiation of the Wake-Up protocol: 8.1% (epoch 2) vs. 21.6% (epoch 3), and number-needed-to-MRI for one tPA treatment dropped from 12.3 to 4.6. In epochs 2 vs. 3, MRI order-to-scan time decreased (28 vs 23 minutes, P=0.039), indicative of process improvement over time. Across all epochs, hMRI indication of WU-UW (vs. SM) was associated with shorter door-to-hMRI completion (68 vs. 83.5 minutes, P=0.041) and shorter door-to-needle time (76 vs. 118 minutes; P=0.030), whereas age, NIHSS, and sex were not associated with hMRI efficiency. None of the 13 patients treated with IV tPA developed symptomatic ICH and 92% were discharged to home or inpatient rehabilitation.

Conclusion:
In the final epoch, < 5 MRIs were performed for one tPA treatment, suggesting that a hMRI protocol may improve with time and increased utilization, justifying the use of hMRI to increase patient eligibility for IV tPA. WU-UW stroke indications for hMRI may predict shorter hMRI process and faster treatment times.
Abstract TP252: Extended Window TPA is Safe at Community Emergency Departments via Telestroke
Authors: Jeevarajan Jerome A , Zha Alicia M , Zhu Liang , Ankrom Christy M , Trevino Alyssa D , Joseph Michele M , Malazarte Rene M , Bambhroliya Arvind B , Cossey TC D , Savitz Sean I , Wu Tzu-Ching , Jagolino-Cole Amanda L
Published: June 2021

Introduction:
Recent studies support tPA for acute ischemic stroke (AIS) patients presenting beyond 4.5 hours from last known well (LKW), if established infarct is not evident on advanced imaging. Many community hospitals, where AIS patients may be managed via telestroke (TS), lack advanced imaging capability and hesitate to administer off-label tPA. In our TS network, physicians adhere to an extended window tPA (EW) protocol also used in the hub emergency room; eligibility includes NIHSS≤25, <1/3 MCA territory hypodensity on CT brain, and off-label tPA consent. Here, we characterize patients receiving EW via TS and investigate safety.

Methods:
We identified 1,150 AIS patients who received tPA via TS (9/2015-12/2018). We compared baseline characteristics between patients who received EW (arrival >4.5 hrs) and those who received standard window tPA (SW, arrival ≤4.5 hrs). We explored clinical outcomes and describe incidence of adverse effects from tPA.

Results:
Forty patients received EW, with median ASPECTS of 9 (Q1-Q3: 9-10). Median LKW to arrival time was 491 mins with EW and 66 mins with SW (p<0.0001, Table 1). EW led to few tPA complications; symptomatic intracranial hemorrhage incidence was 2%. EW was given for more severe stroke than SW (median NIHSS 10 vs 7, p=0.011). Both groups had comparable baseline characteristics, except a higher rate of tobacco use with EW. EW patients had longer length of stay (median 5 vs 3, p=0.023) and were more likely to be discharged to rehab than home (OR: 2.05 (1.01 4.15), p=0.046), however a small number of EW patients precludes in-depth comparative outcomes analysis.

Conclusions:
Our data suggest that EW is safe via TS for select patients with favorable CT, in settings that may lack advanced imaging capability. A specified mismatch between NIHSS and acute ischemia on plain CT is not part of our EW protocol, however EW is more likely given for severe stroke in our TS network. Small sample size warrants further study on clinical outcomes.
Abstract TP26: Time Metrics in Stroke Therapy a Call for Standardization
Authors: Psychogios Marios , Sahlmann Imke , Zapf Antonia , Schmitz Leonie , Liman Jan , Styczen Hanna , Brehm Alex
Published: June 2021

Introduction:
The effect of in-hospital time-metrics, such as door to reperfusion, on the clinical outcome of thrombectomized patients was clearly demonstrated in several large randomized controlled trials (RCTs). Although being powerful predictors of outcome, in-hospital time-metrics and the measurement of the most important time-points “door”, “imaging”, “groin” and “reperfusion” were never standardized, resulting in low comparability across trials. The aim of this study was to analyze different definitions of time-points used in large RCTs and investigate in our patient cohort whether they predict outcome or treatment response.

Methods:
We derived various definitions for the time points “door”, “imaging”, “groin” and “reperfusion” from RCTs, which evaluated the efficiency of mechanical thrombectomy between 2015 - 2018. Based on these definitions, we deducted three different timing paradigms. Data of 352 patients, which underwent thrombectomy at our center between January 2014 and October 2017, were retrospectively screened. Of these 352 patients, we excluded 102 patients due to insufficient data. For the remaining 250 patients door to groin, door to imaging, door to reperfusion, imaging to reperfusion and groin to reperfusion times were calculated according to the different timing paradigms and compared using ANOVA. Association between patient characteristics and time intervals, outcome and successful reperfusion (mTICI ≥ 2b) were modeled by using negative binominal regression.

Results:
Substantial differences were found in the definition of “reperfusion” across the different RCTs, while no study had an exact definition of “groin”. One paradigm resulted in a significant lower median groin-to-reperfusion time (17min vs. 40 and 44.5 min, respectively; p<0.001), Outcome was predicted differently by the individual paradigms. Age, mRS and NIHSS at admission, anesthesia, intravenous thrombolysis and groin to reperfusion time had a relevant impact on mRS at discharge.

Conclusion:
Standard definitions of “groin” and especially “reperfusion” are pivotal to ensure comparability between future studies.
Abstract TP262: Pre-Hospital VAN Large Vessel Occlusion Screening Tool Predicts Larger Intracerebral Hemorrhage
Authors: Shadman Arash , Mozumder Aaisha , de Leonni Stanonik Mateja , Patterson Michele , Wampler David , Stringfellow Michael , Kidd Emily , Miramontes David , Cope Steven , Baker Cheryl , Blanchette Adam , Birnbaum Lee
Published: June 2021

Introduction:
An EMS validation study in San Antonio, Texas previously evaluated the Vision Aphasia Neglect (VAN) screen to identify large vessel occlusion (LVO) in the prehospital setting. Because it may be used in the field to bypass hospitals for higher level care, VAN’s performance with stroke mimics, specifically intracerebral hemorrhage (ICH), is important in stroke systems of care. The goal of this study was to determine if a positive VAN assessment correlated with larger ICH.

Methods:
Paramedics from two San Antonio EMS agencies documented a VAN assessment from June 2017 to April 2019 for all EMS stroke alerts less than 6 hours from last known well. The prehospital VAN score, emergency department advanced neuroimaging interpretation, and hospital discharge diagnosis were collected from three comprehensive stroke centers. Stroke mimics and hemorrhages were included. ICH volume, location, and presence of intraventricular hemorrhage (IVH) were recorded. ICH volume and location were dichotomized by the median value and infratentorial versus supratentorial, respectively. Descriptive statistics were used for continuous data, and categorical data was analyzed by Fisher’s exact test.

Results:
VAN scores were recorded for 215 EMS activated stroke alerts, of which 131 (60.9%) were VAN positive and 23 (10.7%) were ICH. All were hypertensive etiologies except one arteriovenous malformation related hemorrhage. ICH mean and median values were 15.3 ml and 10.3 ml (range 0.3 - 51 ml), respectively. Of the 23 ICH cases, IVH was present in 7 (30%), and infratentorial location was noted in 4 (17%). Fisher’s exact test for VAN and ICH (categorized as ≥ or < median volume) was significant (0.027, p<0.05). However, VAN versus both ICH location and presence of IVH was non-significant.

Conclusion:
In this prospective EMS validation study, a pre-hospital VAN positive assessment predicted larger ICH volumes. Although VAN was designed to identify LVO, pre-hospital triage of ICH is an additional benefit of this screening tool. A false positive VAN assessment for LVO may signify a larger ICH, which is often transferred to higher level centers as standard of care. Thus, VAN perform well for both ischemic and hemorrhagic hospital bypass protocols.
Abstract TP263: Mobile Stroke Unit Operation in a Topographically Variable County
Authors: Spokoyny Ilana , English Joey , Im Jenny , Delgadillo Jorge , Pancoska Eric , Entsminger Trish , Barazangi Nobl
Published: June 2021

Introduction:
Mobile Stroke Units (MSUs) require a level surface for CT scanner operation. The MSU is equipped with a user-friendly leveling system which can compensate for a front-to-back maximum angle of 3.8° or a 6.6% grade, and a left-to-right maximum angle of 10.4° or an 18.4% grade, but this still requires the unit be parked on a relatively flat location. Previous reports of MSU operations have been from topographically flat and fairly uniform communities. In San Mateo County, many neighborhoods are topographically variable which makes access challenging. This study describes process improvements made to ensure successful and efficient treatment of stroke patients on the MSU in this environment.

Methods:
A workflow change was instituted to adapt to locations which the MSU either could not directly access due to size, or at which the grade was clearly greater than could be accommodated for using the internal leveling system. For particularly hilly areas, pre-specified “staging” locations were identified. These locations met the following criteria: flat grade, adequate space for the MSU, requiring minimal additional driving time en-route to destination hospital. The locations were scouted with the assistance of local EMS and Fire Departments. The MSU team evaluates the patient at the original location, and takes the patient onboard the MSU if the patient meets criteria for transport. Then, the MSU drives with the patient to the pre-specified “staging” location, where the CT scan is performed and rt-PA treatment decision is made.

Results:
Employing this process improvement has eliminated additional on-scene time spent looking for a more level location. Clear algorithms, when challenging locations are encountered, allow for smooth workflow and limit delays to treatment. Additionally, in hilly areas, cellular service is often unreliable, so traveling to a “staging” location has often improved connectivity for telemedicine.

Conclusion:
This study is the first to describe a standardized workflow solution to challenging topography. As MSUs become more prevalent, reproduction of this process improvement may prove useful to other counties facing similar challenges, while improved leveling capabilities are being concurrently developed.
Abstract TP266: Ischemic Stroke Induces Striking Heterogeneity in the Inflammatory Leukocyte Infiltrate Across the Core and Penumbra
Authors: Nadkarni Neil A , Batra Ayush , Muller William A , Sullivan David P
Published: June 2021

Background:
Current therapies for ischemic stroke focus on reperfusion but do not address the acute inflammatory response. Previous clinical trials aimed at modulating the inflammatory milieu by disrupting leukocyte infiltration failed to show clinical efficacy. One possible explanation for this unexpected shortcoming is an incomplete understanding of the precise spatio-temporal underpinnings of leukocyte extravasation and infiltration.

Methods:
Here we describe the evolution of the inflammatory response in a mouse transient middle cerebral artery occlusion (tMCAO) stroke model at 0, 1, 2 and 3 days post reperfusion. We used wide field and confocal immunofluorescence microscopy to examine the exact nature and location of the invading myelomonocytic populations, with close examination of the leukocyte position with regard to the brain vasculature and the perivascular space.

Results:
Our findings suggest that the vast majority of infiltrating myelomonocytic cells escape the perivascular compartment and enter the parenchyma. Interestingly, leukocyte extravasation and accumulation in the subcortex occurred over several days. Dramatic heterogeneity in the inflammatory infiltrate was observed across the infarcted tissue, but also in the surrounding penumbra and adjacent cortical surface. In addition, triphenyl tetrazolium chloride staining, a common indicator for infarcted tissue, did not correlate with the amount or location of leukocyte infiltration.

Conclusion:
Taken together our findings demonstrate that the infiltration of leukocytes dynamically evolves over several days following reperfusion. Furthermore, leukocytes infiltrate in a heterogeneous pattern that does not correlate well with traditional markers of cellular dysfunction. A better understating of the precise spatio-temporal infiltration of inflammatory cells could help inform the next generation of therapeutic interventions.
Abstract TP271: Sex Specific Regulation of Astrocytic Mitochondrial Function by Microrna (mir)20a-3p Under Ischemic Conditions
Authors: Branyan Taylor , Srinivasan Rahul , Sohrabji Farida
Published: June 2021

Introduction:
Astrocytes from middle-aged reproductively senescent rats, who typically have larger infarcts after stroke, have been shown to have a reduced functional capacity for glutamate clearance and production of trophic factors compared to astrocytes from adult rats, who typically have smaller infarcts. Epigenetic analysis revealed greater H3K4 trimethylation of the promoter region of the mir17-92 cluster in adult astrocytes, and qRT-PCR analysis confirmed increased expression of all members of this cluster including a 240-fold elevation of mir20a-3p. Intravenous injection of mir20a-3p mimics 4h after induction of ischemia improved stroke outcomes in middle-aged female rats. Bioinformatics indicate that mir20a-3p modulates many mitochondrial genes, including Glycerol-3-Phosphate Acyltransferase, Cytochrome B5 Type B, Acyl-coenzyme A synthetase. This study tested the effect of mir20a-3p on mitochondrial function in astrocytes in normoxic and ischemic conditions.

Methods:
Male and female human astrocyte cultures were assigned to normoxic (21% O
2
, 25 mM glucose) or ischemic (1% O
2
, 0 mM glucose) conditions for 6h. Cells were treated with 50 nM mir20a-3p, 50 nM scrambled control miR or vehicle. Mitochondrial function was assessed by Fluorescent Recovery After Photobleaching (FRAP).

Results:
Imaging of astrocytes indicates FAM-labeled mir20a-3p uptake, and qRT-PCR analysis indicates a significant sex difference in mir20a-3p expression after OGD that recapitulates the
in vivo
phenotype. Treatment with mir20a-3p accelerated fluorescent recovery compared to cells treated with scrambled miR or vehicle in normoxia and OGD for both sexes. A significant sex difference was observed in fluorescent recovery, with the male cells experiencing a dampened effect in response to mir20a-3p or scrambled treatment.

Conclusion:
Since the rate of fluorescent recovery measures mitochondrial membranes continuity, these data suggest that mir20a-3p promotes mitochondrial fusion. If greater continuity of the mitochondrial membrane compensates for the greater energy demand after stroke, these data may explain why stroke recovery is better in young females compared to males.

Supported by NIH RF1 AG042189 to FS and a TAMU Graduate Merit Fellowship to TB
Abstract TP274: Post-stroke Treatment With Docosanoids Promote Functional Recovery, Neurogenesis and Angiogenesis, Attenuate Blood-brain Barrier After Experimental Ischemic Stroke
Authors: Belayev Ludmila , Hong Sungha , Obenaus Andre , Khoutorova Larissa , Mukherjee Pranab , Jun Bokkyoo , Bazan Nicolas G
Published: June 2021

Objective:
Ischemic injury induces neurogenesis in the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of dentate gyrus (DG) promotes the migration of neuroblasts, guided by blood vessels, into the ischemic damaged area. Neurogenesis leads the functional and histological recovery in the ischemic-damaged brain through the proliferation, migration, differentiation and integration of newly generated neural cells into the existing neural circuit. Recently, we have shown that Docosahexaenoic acid (DHA) and Neuroprotectin D1 (NPD1) therapy improves functional and histological outcomes following experimental stroke. It has also been shown that DHA promotes neurite outgrowth of immature neurons, such as embryonic hippocampal cells and embryonic cortical cells. The objective of this study was to explore underlying mechanisms of docosanoid neuroprotection after cerebral ischemia.

Methods:
Male Sprague-Dawley rats were anesthetized with isoflurane/nitrous oxide, underwent 2h of middle cerebral artery occlusion (MCAo) and treated with DHA (5mg/kg, IV) or NPD1 (5μg/per rat, ICV) and vehicles 1h after. Neuro-behavioral assessments were conducted on days 1, 2, 3 and on weeks 1, 2, 3 or 4. BrdU was injected on days 4, 5 and 6, immunohistochemistry was performed on week 2 or 4, MRI on day 7 and lipidomic analysis at 4 and 5h after onset of stroke.

Results:
DHA improved short- and long-term behavioral functions and reduced cortical, subcortical and total infarct volumes (by 42%, 47% and 31%, respectively) after 2 weeks and reduced tissue loss by 50% after 4 weeks. DHA increased the number of BrdU
+
/Ki-67
+
, BrdU
+
/DCX
+
and BrdU
+
/NeuN
+
cells in the cortex, subventricular zone and
dentate gyrus
and potentiated NPD1 synthesis in the penumbra at 5h after MCAo. NPD1 improved behavior, reduced lesion volumes, protected ischemic penumbra, increased NeuN, GFAP, SMI-71 positive cells and vessels, axonal regeneration in the penumbra and attenuated blood-brain barrier (BBB) after MCAo.

Conclusion:
We conclude that docosanoid administration increases neurogenesis, angiogenesis, activates NPD1 synthesis in the penumbra and diminishes BBB, which correlates to long-term neurobehavioral recovery after experimental ischemic stroke.
Abstract TP28: Intravenous Thrombolysis is Associated With Better Functional Outcomes in Endovascular Thrombectomy Patients Requiring Multiple-Passes to Achieve Reperfusion
Authors: Blair Christopher , Cappelen-Smith Cecilia , Cordato Dennis , Edwards Leon , Mitchelle Amer , Cheung Andrew , Wenderoth Jason , Manning Nathan
Published: June 2021

Introduction:
In patients with anterior circulation stroke with large vessel occlusion (LVO), recent data suggest that successful reperfusion (mTICI≥2b) after a single device pass results in more favourable functional outcomes in comparison to patients requiring multiple passes. It is unclear if this effect represents an epiphenomenon or a true independent effect.

Methods:
A prospectively maintained database of EVT was interrogated for patients presenting with anterior circulation LVO with onset to groin puncture times of ≤ 6 hours from January 2016 to March 2019. Three-month functional outcomes were compared between first-pass reperfusion and multiple-pass reperfusion patients using logistic regression.

Results:
A total of 169 patients were identified (mean age 71 yrs, 44% female, median NIHSS 17, intravenous thrombolysis (IVT) in 47%). Successful reperfusion (mTICI≥2b) was achieved with the first-pass (FP) in 80 patients (47%) and multiple-passes (MP) in 89 patients (53%). First pass patients had better outcomes when compared to MP patients (mRS 0-2 71% vs 31%, p < 0.001). No difference in functional outcomes was seen between FP patients who received IVT and those that did not (mRS 0-2 68% vs 75%, p = 0.459). Multiple-pass patients who received IVT achieved higher rates of functional independence than those who did not (mRS 0-2 40% vs 27%, p = 0.035).

Conclusion:
Intravenous thrombolysis may improve functional recovery in EVT patients requiring multiple-passes to achieve reperfusion. Prospective studies should be considered.
Abstract TP283: Phosphorylation of IRF5/4 by IRAK4/MyD88 Regulates Microglial Inflammatory Responses to Ischemia
Authors: Ngwa Conelius , Sharmeen Romana , Xu Yan , Liu Fudong
Published: June 2021

Introduction:
Interferon Regulatory Factors 5 and 4 (IRF5/4) have been suggested to play a determinant role in regulating pro-inflammatory (M1) or anti-inflammatory (M2) microglia/macrophage response. However, how IRF5/4 signaling are activated in these phagocytes has not been well understood. Our previous study has shown an increased level of phosphorylated-IRF4 in both the cytosolic and nuclear fraction of cultured microglial homogenates after ischemia, suggesting phosphorylation is important for IRF4 activation. Interleukin-1 receptor associated kinase 4 (IRAK4) and the adaptor protein MyD88 are the upstream signals of IRF5. In the present study we hypothesized that IRAK4/MyD88 phosphorylate IRF5/4 in ischemic microglia and trigger the translocation of IRF5/4 from the cytoplasm to the nucleus, to promote expression of inflammatory mediators.

Methods:
Spontaneously Immortalized (SIM)-A9 or primary microglia from C57BL/6 mice were cultured and exposed to oxygen-glucose deprivation (OGD) for 4 hours; after OGD the cells were reperfused overnight with glucose-containing medium in room air. Phosphorylation of IRF5/4 by IRAK4 was determined with IRAK4 inhibitor (ND-2158). The interaction between IRAK4/MyD88 with IRF5/4 and the nuclear translocation of phosphorylated-IRF5/4 were examined by immunocytochemistry (ICC) and co-immunoprecipitation (Co-IP)/Western Blots (WB). Production of inflammatory cytokines was measured by ELISA in the culture medium.

Results:
WB showed more robust nuclear p-IRF5 signals; ELISA found increased level of TNFα, IL-1β, and IL6 in OGD vs. normoxic microglia. A similar pattern was observed for p-IRF4 nuclear translocation but with moderately increased anti-inflammatory cytokine (IL-4 and IL-10) levels with OGD. Co-IP revealed a higher ratio of p-IRF5/4 over total IRF5/4 in the nuclear vs. cytosol fraction, and interactions of IRAK4/MyD88 with both IRFs. ND-2158 treatment led to decreased phosphorylation of IRF5/4 after OGD compared to the vehicle group.

Conclusion:
IRAK4/MyD88 complex phosphorylates microglial IRF5/4 which subsequently mediates the production of inflammatory cytokines after ischemia. Manipulation of IRF5/4 signaling potentially represents a novel therapeutic strategy for stroke.
Abstract TP285: Dimethyl Fumarate Protects Against Hypoxic-Ischemic Brain Damage and Attenuates Reactive Gliosis in an Nrf2-Dependent Manner: Focus on Hippocampal Injury
Authors: Liu Lei , Vollmer Mary K , Kelly Marie G , Fernandez Victoria M , Fernandez Tyler G , Dore Sylvain
Published: June 2021

Introduction:
Recently, based on the purported antioxidative and anti-inflammatory properties, dimethyl fumarate (DMF) has exhibited protective potential in various acute and chronic neurological conditions. Its effect on cerebral ischemia and underlying mechanisms remain inconclusive; furthermore, increasing evidence indicates the involvement of the transcriptional factor Nrf2.

Hypothesis:
DMF plays a beneficial role on hippocampal neuronal loss and reactive gliosis induced by hypoxia-ischemia (HI) through an Nrf2-dependent mechanism.

Methods:
Adult wildtype (WT) and Nrf2
-/-
mice were pretreated with DMF for 7 days prior to HI.

Results:
At 24h after HI, DMF significantly reduced infarct volume (52.5±12.3%), brain edema (61.5±17.4%), and hippocampal CA1 neuronal degeneration, and induced expressions of Nrf2 target proteins in the WT (p<0.01), but not in the Nrf2
-/-
mice. Such hippocampal neuroprotective benefits were also observed at 6h and 7 days after HI. The dynamic attenuation of reactive gliosis in microglia and astrocytes correlated well with this sustained neuroprotection in an Nrf2-dependent manner. In both early and late stages of HI, the astrocytic water transport channel protein aquaporin 4 was also attenuated after HI in WT, but not Nrf2
-/-
, mice treated with DMF.

Conclusion:
Together, DMF confers robust and prolonged Nrf2-dependent neuroprotection against ischemic hippocampal damage. The salutary Nrf2-dependent attenuation of reactive gliosis may contribute to this neuroprotection, offering new insights into the cellular basis of an Nrf2-targeting strategy for stroke prevention and/or treatment. As DMF is already clinically approved for multiple sclerosis, it makes it a unique potential prototypical example of drug repurposing for treatment and/or prevention of stroke damage.
Abstract TP300: Implementation of Stroke Pathways to Reduce Length of Stay, Cost, Readmissions, and Mortality
Authors: Strauss Jayme , Waisbrot Andrew , D'Amour Daniel , Starosciak Amy K
Published: June 2021

Introduction:
Acute stroke is a major contributor to healthcare costs. In 2012, estimated direct costs associated with stroke was $71B, which is projected to double to $184B by 2030. As healthcare evolves and reimbursements decrease, cost control in disease specific populations is critical. In November 2017, length of stay (LOS) peaked at 5.78 days, as did variable and total cost/case (Table). In fiscal year 2017 the 30-d readmission rate was 9% and the mortality rate was 12%. Compliance with stroke admission order sets was at 55%.

Methods:
A multidisciplinary committee was formed in February 2017 to develop standardized, evidence-based clinical pathways for three populations: Ischemic stroke (IS) treated with IV tPA, TIA/IS without IV tPA, and intracerebral hemorrhage. The team met biweekly to standardize clinical pathways, decrease time to follow-up imaging, focus on physician order set utilization, and control costs. A comprehensive education program for all clinical staff was completed; official implementation of the pathways was in November 2017. A stroke financials team meets monthly to continue to look at opportunities and transitions of care. We reviewed a retrospective financial report of all in-hospital cases coded as MS-DRG 61-69 from 12/2017 through 7/31/2019 and compared it the 11/2017 report.

Results:
A total of 83 cases were available for 12/2017 and 2192 for 1/2018 through 7/2019. There was a reduced LOS by 26% (4.34 days), reduced variable cost/case by 24% ($5,958), reduced total cost/case by 23% ($13,790), reduced the 30-d readmission rate to 6%, and reduced the mortality rate to 4%. Case mix index was 12% higher at 1.3272 (vs. 1.2055 previously). Order set compliance improved to 94% (Table). A total cost saving dollar realization of $4.5 million.

Discussion:
Standardization of stroke clinical pathways led to improved order set compliance, almost 1/4 reduction in variable and total costs per case, shortened LOS, and reduced mortality and readmission rates.
Abstract TP309: Utilization of IV-rtPA and Endovascular Therapy Use on Off-Hours vs. On-Hours: An Age Group Comparison
Authors: Patel Smit D , Patel Neel , Saini Vasu , Pervez Mubashir , Otite Fadar Oliver , Asdaghi Negar , Khandelwal Priyank
Published: June 2021

Introduction:
Previous studies have yielded inconsistent results on whether weekend admission impacts the utilization of EVT and IV-rtPA. There is limited data available of whether age groups difference affects on use of IV-rtPA and EVT admitted during the off-hours. Our study aimed to investigate whether admission during the off-hours has any effect on the EVT & IV-rtPA utilization and is distributed uniformly across all age groups?

Method:
All adults admitted to US hospitals from 2005-2015 with a primary diagnosis AIS (n=4,520,516) were identified from the Nationwide Inpatient Sample using ICD-9 CM codes. Discharge weights were used to generate national estimates. On-hours vs. off-hours were defined using the weekend variable. Age groups were divided into 18-39, 40-59, 60-79 and ≥80 years. An age groupwise multivariable logistic regression models were used to compare odds of EVT and IV-rtPA use between on-hours vs. off-hours.

Result:
Total 4.5 million AIS population comprised 2.1% of 18-39 years, 20.0% of 40-59 years, 44.1% of 60-79 years and 34.0% of ≥80 years. Off-hours admissions comprised 25.7% of total AIS. Univariate analysis of off-hours vs. on-hours effects showed EVT utilization was 2.2% vs. 2.3% (P=0.50) and IV-tPA use was 7.9% vs. 7.3% (P=0.18) in 18-39 years. In 40-59 years age group, EVT 1.19% vs. 1.17% (P=0.74) and IV-tPA 6.2% vs. 5.7% (P <0.0001). In 60-79 years, EVT 0.95% vs. 0.96% (P=0.87) and IV-tPA 5.5% vs. 5.0% (P <0.0001) and in ≥80 years, EVT was 0.5% vs. 0.6% (P=0.12) and IV-tPA was 4.7% vs. 4.4% (P <0.0001). After a multivariable adjustment of patients and hospital characteristics, odds of EVT utilization was 0.85 (P=0.18) in 18-39 years, 0.92 (P=0.13) in 40-59 years, 0.91 (P=0.014) in 60-79 years and 0.84 (P=0.003) in ≥80 years. While in IV-tPA group, odds of IV-tPA use was 1.09 (P=0.16) in 18-39 years, 1.08 (P=0.001) in 40-59 years, 1.09 (P <0.0001) in 60-79 years and 1.07 (P=0.002) in ≥80 years.

Conclusion:
Our study concludes that there is a lower rate of EVT performed during off-hours in the age groups of 60-79 and ≥ 80 years old. However, There was no difference reported in the use of EVT in the younger population. It’s also interesting to note that there is a higher use of IV-rtPA during the off-hours in all age groups except age group 18-39 years.
Abstract TP313: A Metro Chicago Learning Collaborative Model to Improve Smoking Cessation Rates in Stroke Patients
Authors: Bulwa Zachary , Rainey Joy , Kruse Donna , Klassman Lynn , Sednew Renee , O'Neill Kathleen , Scharnott Michelle C
Published: June 2021

Background:
National guidelines for stroke care recommend that patients discharged with a stroke who have a history of smoking receive smoking cessation intervention prior to hospital discharge. However, less is known about the types of intervention provided and subsequent outcomes post-discharge. The Metro Chicago Smoking Cessation Initiative Pilot aimed to improve understanding of smoking cessation interventions provided at discharge, smoking behavior at 30 days post-discharge, and best practices and barriers for reducing smoking rates in stroke patients discharged from 20 Chicago area hospitals.

Methods:
A review of smoking cessation interventions provided at discharge and smoking cessation outcomes post-discharge for stroke patients discharged between August 1, 2018 and July 31, 2019 at 20 Chicago area participating hospitals was conducted using Get With The Guidelines® Stroke. The pilot used a Learning Collaborative model that included a quality improvement leader, smoking cessation/health behavior content experts, reporting of experiences and data, and sharing of best practices. All hospitals were required to attend quarterly online learning sessions and use Get With The Guidelines® Stroke for data entry.

Results:
Preliminary results from the 20 participating hospitals suggest smoking cessation counseling is the most commonly delivered intervention at discharge. Of the patients reached at 30 days post-discharge, 75% of those who reported at history of smoking at the time of their stroke were still using tobacco products. However, nearly 50% of those patients reported having made at least one attempt to quit.

Conclusions:
Preliminary results from this pilot project highlight the need for improved tracking of smoking cessation interventions provided at discharge and associated smoking behavior post-discharge, as well as the benefits of regional collaboration for identifying and implementing best practices.
Abstract TP314: Baseline Thrombocytopenia in Patients With Acute Coronary Syndrome: Does it Affect Following Cerebrovascular Event Rates?
Authors: Chao Chiehju , Chiang Chiachun , Khalid Muhammad , Fortuin David
Published: June 2021

Introduction:
Baseline thrombocytopenia (TP) is a common condition in patients with acute coronary syndrome (ACS) and acute ischemic stroke and has been shown to increase mortality. The effect of baseline TP on cerebrovascular events following initial ACS event is not well studied.

Methods:
We retrospectively reviewed all patients identified from the institutional NCDR Chest Pain registry database at Mayo Clinic Arizona from Oct 2015 to Sep 2018. Patients were classified into TP (platelet <150) and control (platelet > 150) groups for clinical outcome (stroke/TIA and bleeding events) analysis. P-value < 0.05 is considered significant.

Results:
Five hundred and thirty-six patients were included for final analysis. Patient demographics and clinical outcomes are shown in Table 1. The rates of dual antiplatelet therapy (DAPT) prescription at discharge (TP vs. control: 68.1% and 75.4%, P=0.197), stroke/TIA (1.3% vs. 2.4%, P=1.000) and recurrent myocardial infarction (11.1% vs. 11.2%, P=1.000) were similar between the two groups. The TP group has more bleeding events compared to control (Figure 1).

Conclusions:
In patients with ACS, baseline TP does not affect stroke/TIA events but is associated with higher bleeding rate. The results could not be explained by the DAPT or anticoagulation use alone. Further studies are needed to investigate the pathophysiologic correlation of thrombocytopenia, DAPT, and stroke in ACS patients.
Abstract TP316: Urban Crural Comparisons of Treatments and Outcomes for Ischemic Cerebrovascular Diseases
Authors: Wang Chunjuan , Li Zixiao , Gu Hongqiu , Jiang Yong , Meng Xia , Li Hao , Wang Yongjun
Published: June 2021

Background:
Little is known about healthcare quality and patient outcomes of ischemic cerebrovascular diseases between urban and rural areas in China during the past decade.

Methods:
We used a two-stage random sampling method to create a nationally representative sample of patients in China hospitalized for ischemic stroke (IS)/ Transient ischemic attack (TIA) in 2005, 2010, and 2015. Firstly, we used simple random sampling to obtain a list of participating hospitals in 2 urban and 3 rural strata. Secondly, we obtained medical records at each hospital on clinical profiles, tests, treatments and outcomes using a systematic sampling approach. We weighted our findings to explore rural-urban disparities from 2005 to 2015.

Results:
A total of 30 827 patients were sampled from 189 hospitals with 14 418 (46.8%) from urban and 16 409 (53.2%) from rural. We observed a decreased disparity between urban and rural in eligible patients receiving antiplatelet and anticoagulant for atrial fibrillation (AF) (both P
trend
<0.0001), a diminished disparity of statins use by 2015 (70.9% in urban versus 69.9% in rural; P=0.1852) and an emerging disparity of antihypertensive treatment (P
trend
<0.0001). The disparities of composite score of tests (from 0.24 in urban vs 0.18 in rural to 0.30 in urban vs 0.33 in rural, P
trend
<0.0001) and in-hospital treatments (from 0.45 in urban vs 0.49 in rural to 0.70 in urban vs 0.69 in rural, P
trend
<0.0001) were all decreased from 2005 to 2015. In-hospital mortality have both decreased significantly in urban or rural areas, the adjusted risk of in-hospital mortality in urban was higher than rural in both 2005 (OR [95% CI]: 2.26 [1.12-4.55], p=0.0223) and 2015 (OR [95% CI]: 2.64 [1.30-5.36], p=0.0070), however, the trend of disparity was not significant (P for interaction =0.9527).

Conclusion:
Although urban-rural disparities in evidence-based treatments for IS/TIA patients have largely been eliminated, substantial gaps in quality of care persist in both settings.
Abstract TP319: Risk Factors of Post-stroke Epilepsy
Authors: Danilova Tatyana , Khasanova Dina
Published: June 2021

Purpose:
The aim of the study was to identify the risk factors for seizures in patients with ischemic stroke using clinical, functional, neuroimaging research methods.

Materials and methods:
The results of the complex survey of 468 patients suffering from ischemic stroke (256 patients experienced epileptic seizures and 203 experienced no epileptic seizures) are presented. The diagnostic procedures included clinical evaluation, magnetic resonance imaging, electroencephalography, extracranial and transcranial Doppler sonography. In addition the assessment of the rate of sodium lithium countertransport (the marker of genetically determined on transport mechanisms of cell membranes) in patients with c ischemic stroke with the development of epileptic seizures and no seizures was carried out.

Results:
The focal seizures are the most common (92,5%). Cortical ischemic brain lesions prevailed in patients with seizures (81,1%), whereas in the control group cortex was affected in 38,9% patients (χ2=89.2, <0,001). Stenosis of cerebral arteries was more common in patients with epilepsy (82.3%) compared to patients without seizures (74.4%, <0.05). Reduced cerebrovascular reactivity (CVR) in vertebro-basilar basin was more frequently detected in patients with seizures (85.9%, p<0.001) compared to controls (71.6%). CVR < 10% was registered in 33.8% patients with seizures versus 13.4% controls (p<0.001). Patients with epileptic seizures showed cerebral perfusion reduction mostly in vertebro-basilar basin (85.9%) rather than in carotid basin (61.2%, p<0.001). Patients experienced epileptic seizures had high rates of sodium-lithium antitransport (> 346 μmol/liter cells x hour) more often than patients without epileptic seizures (52,6% and 35,5%, respectively, <0,05). Patients experienced epileptic seizures with high rates of sodium-lithium antitransport had a higher seizure frequency than patients with low rates of sodium-lithium antitransport.

Conclusion:
Thus, cortical ischemic brain lesions, significant stenosis of cerebral arteries, predominant perfusion reserve reduction in the posterior cerebral circulation, as well as a high rate of sodium lithium countertransport may be considered as risk factors for post-stroke epilepsy.
Abstract TP320: Different Response Times to Intrahospital Stroke Between Medical and Surgical Infirmaries: A Dunning-Kruger Effect?
Authors: Perissinotti Iago N , Salvadori Fernanda A , Fonseca Barbara S , Calderaro Marcelo
Published: June 2021

Rapid response teams (RRT) improve speed and quality of urgent inpatient care. Nonetheless, its effectiveness depends on adequate problem identification and fast triggering of institutional procedures. Differences in patient profiles and team experience between medical (Me) or surgical (Su) wards may influence the response times to suspected intrahospital strokes. From January/2016 through April/2019, we retrospectively analyzed data in a large tertiary hospital in Brazil. There were proportionally more callings for suspected strokes in medical wards (36/281 [13%] Me vs. 16/619 [2%] Su, p<0.001) in relation to the total of calls for any reason, while the ratio of diagnostic confirmation was similar (19/36 [52%] Me vs. 10/16 [62%] Su, p=0.495). Ischemic strokes were more prevalent in both infirmaries (17/19 [89%] Me vs. 8/10 [80%] Su, p=0.43). While not statistically significant, there were numerical differences between time to symptom recognition and the interval between recognition and triggering of the RRT. Medical ward teams recognized symptoms on average 108 minutes after the presumed onset versus 164 minutes in surgical wards. Paradoxically, surgical teams more promptly called RRT after recognition, on average 93 versus 172 minutes. There were no statistical differences in the ratio of ischemic strokes submitted to intravenous thrombolysis (11/17 [35,3%] Me vs. 1/8 [12,5%] Su, p=0.25) or mechanical thrombectomy (2/17 [11,8%] Me vs. 0/8 Su, p=0.45), however it is possible that the small number of events (52 calls in 40 months) led to low statistical power. This study suggests there may be differences in initial responses to suspected intrahospital strokes between different ward profiles. These might be secondary to variations in patient characteristics and team education, but also be caused by a Dunning-Kruger phenomenon (i.e. a higher perception of knowledge on stroke care leading to delays in triggering institutional workflows). Identifying these divergences in further larger, prospective trials can help develop individualized interventions to improve the quality of care in these medical emergencies.
Abstract TP323: The Role of Ejection Fraction in 90 Day Functional Outcome in Acute Ischemic Infarction Patients Receiving Acute Stroke Therapy
Authors: Ranasinghe Tamra , Meyer Brett , Lane Richard , Meyer Dawn
Published: June 2021

Background:
Cardiovascular disease is associated with unfavorable outcomes following acute ischemic stroke (AIS). Left ventricularejection fraction (LVEF) alone has not been reported as a significant predictor of unfavorable outcomes in observational studies of AIS.The purpose of this study was to evaluate the relationship between LVEF and 90 day functional outcome in AIS patients who received acute stroke therapy with IV recombinant tissue plasminogen activator (rt-PA), endovascular therapy (EVT), or combination IV rt-PA+EVT.

Methods:
This was a retrospective review of prospectively collected data from the University of California San Diego (UCSD) Stroke registry from October 2014-June 2019. Analysis included all patients for whom a stroke code was activated and who had a transthoracic echocardiogram (TTE) during stroke admission or within the previous 30 days prior to AIS. Acute stroke therapy was defined as 1) IV tPA only; 2) EVT only; or 3) IV tPA + EVT. LVEF function was defined as: low <35%, moderately low 36 -49% and normal >50% on TTE. Primary outcome was modified ranking scale(mRS) at 90 days post stroke. Data was examined for frequencies and distribution. Continuous variables were assessed by Pearson correlation and t test. Kruskal-Wallis or ANOVA were used to evaluate group differences. ANCOVA was used for adjusted analysis.

Results:
In the 227 patients identified, low EF patients were more likely to have atrial fibrillation (61.9%, p=.004) and lower mean admission systolic blood pressure (132.6, p=0.009). LVEF was not significantly associated with 90 day outcome in all treated patients in both unadjusted (p=0.992) and adjusted (p=0.62). LVEF was not significantly associated with 90 day outcome for individual acute stroke therapy groups both unadjusted and adjusted. mRS at 90 days was significantly associated with baseline NIHSS (p<0.001), age (p=0.002), and treatment with IV tPA (p=0.01).

Conclusion:
In this study, LVEF was not independently associated with 90 day functional outcome in AIS patients who received acute stroke therapy. Further studies in more heterogenous samples are warranted to assess the relationship between LVEF and outcome in all stroke populations.
Abstract TP324: Early Termination of Acute Stroke Randomized Controlled Trials Published Between 2013 and 2018: A Systematic Review
Authors: Strong Brent , Oostema John A , Nikroo Nadia , Hussain Murtaza , Reeves Mathew J
Published: June 2021

Introduction:
A priori
sample size determination is an essential step in designing randomized controlled trials (RCTs). Failure to reach pre-planned sample size introduces risk of both falsely negative and spuriously positive findings. We undertook a systematic review of contemporary acute stroke trials to document the prevalence and reasons for termination of trials prior to completion of enrollment.

Methods:
We searched MEDLINE for RCTs of acute stroke therapy published between 2013 and 2018 in 9 major journals. Manuscripts describing the final primary results of phase 3 and large phase 2 trials of any therapeutic intervention were eligible for inclusion. Study characteristics, including the presence of a data monitoring committee (DMC) and stopping rules, risk-of-bias assessment, funding sources and conflicts of interest, were abstracted from published manuscripts and trial protocols by two independent reviewers. The prevalence of and reasons for early termination were quantified. Multivariable logistic regression was used to identify study-level predictors of early termination.

Results:
Of 756 hits, 60 were eligible for inclusion, 21 (35%) of which were terminated early. Among the trials stopped early, 10 (48%) reported stopping for benefit or newly available evidence while 11 (52%) were terminated for futility; 20 (95%) reported a DMC and 17 (81%) reported the use of a pre-specified statistical stopping rule. Factors associated with early termination included study location in North America, larger planned sample size, and industry funding (Table). Study location in North America and larger planned sample size retained statistical significance in a multivariable model.

Conclusions:
One in three contemporary stroke trials were terminated prior to completion of enrollment. Reasons for termination were evenly split between benefit and futility. Further study is needed to understand the reasons for and impact of early termination on study results.