bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP10: Comparison of 6 mm Diameter and 3-4 mm Diameter Stent Retrievers for Mechanical Thrombectomy in Acute Ischemic Stroke Patients. Is Bigger Better?
Authors: Hassan Ameer E , Sanchez Christina , Ahrar Asad , Chaudhry Saqib A , Qureshi Adnan I
Published: June 2021

Background:
There is controversy regarding the optimal size of stent retriever for achieving timely recanalization in acute ischemic stroke patients.

Objective:
To determine the relationship between stent retriever diameter and procedure time, and rates of recanalization, and functional independence among acute ischemic stroke patients undergoing mechanical thrombectomy.

Methods:
We analyzed data from consecutive acute ischemic stroke patients treated with mechanical thrombectomy derived from a prospective database. Baseline demographic and clinical characteristics, NIHSS score on admission and discharge, intracranial hemorrhage occurrence, and mRS at discharge were analyzed. Thrombolysis In Cerebral Infarction (TICI) scale was used to grade pre and post procedure angiographic recanalization. Procedural time was defined by the time interval between microcatheter placement and recanalization. We compared the rates of thrombectomy attempts, complete recanalization (TICI grade of 3), and functional independence (defined by mRS 0-2) between patients treated with 6 mm and 3-4 mm diameter stent retrievers.

Results:
A total of 230 acute ischemic stroke patients (mean age 71.8 ±12.5; 46.6% women) were treated with stent retrievers. Thrombectomy was performed with a 6mm diameter stent retriever in 107 patients and 3 or 4 mm diameter stent retriever in 123 patients. There were no statistically significant differences in demographics or baseline characteristics, or admission NIHSS score between the two groups. There was a trend towards a fewer number of thrombectomy attempts required with a 6mm diameter stent retriever (p=0.06). There was a higher rate of complete recanalization in patients treated with 6mm diameter stent retriever compared with 3 or 4 mm diameter stent retriever (72% vs 57.7% p=0.02). There was no statistically significant difference in rates of functional independence between the two groups (24.3% vs 25.2% p=0.84) at discharge.

Conclusion:
Among acute ischemic stroke patients undergoing mechanical thrombectomy, use of a 6 mm diameter stent retriever was associated with a higher rate of complete recanalization and a lower number of thrombectomy attempts compared with 3-4 mm diameter stent retrievers.
Abstract WMP105: Human Monocyte Derived Macrophage Phagocytize Eryptotic Erythrocytes in a Phosphotidylserine Dependent Mechanism
Authors: Steinschneider Arthur F , Chang Che-Feng , Askenase Michael H , Ai Youxi , Sansing Lauren H
Published: June 2021

Introduction:
After intracerebral hemorrhage (ICH), erythrocytes contribute to secondary injury by releasing toxic hemoproteins. Our lab has previously shown that blood derived macrophages play an important role in ICH clearance but mechanisms of phagocytosis by human macrophages are unknown. This study aims to quantify eryptotic (phosphatidylserine (PtdSer)-expressing) red blood cells (RBCs) in an
in vivo
model of ICH, and to investigate the mechanisms that play a role in autologous eryptotic phagocytosis by human monocyte derived macrophages (huMDMs).

Methods:
ICH was induced in mice by autologous blood injection. The mice were sacrificed at 1 day after ICH. The brains were separated into hemispheres and digested into a single cell suspension for analysis by flow cytometry. Cells were stained with antibodies to cell surface markers and annexin V to quantify externalized PtdSer expression. Human monocytes were cultured with M-CSF for 7 days to generate huMDMs. Autologous RBCs were heat shocked (HS) to induce eryptosis. The huMDMs were cocultured with HS RBCs, HS RBCs treated with annexin V, or control RBCs. After 1 hour of coculture, the huMDMs were washed, stained and erythrophagocytosis quantified by microscopy.

Results:
The proportion of cells that externalized PtdSer increased by almost 20 fold at day 1 after ICH. Control brains mixed with fresh RBCs and subjected to tissue prep did not show PtdSer expression, ensuring that the PtdSer expression detected was induced in vivo (Fig A). HS RBCs increased PtdSer expression and were efficiently phagocytosed by huMDMs. Treatment of HS RBCs with annexin V to antagonize PtdSer-receptor interactions decreased RBC phagocytosis to levels comparable to control RBCs (Figs B and C).

Conclusions:
In vivo after ICH, erythrocytes externalize PtdSer, a cue to be engulfed by macrophages. Human macrophages phagocytose RBCs in a PtdSer-dependent mechanism. These findings highlight potential targets to enhance ICH clearance.
Abstract WMP106: Soluble CD163 as a Prognostic Marker for Perihematomal Edema Formation and Functional Outcomes in Intracerebral Hemorrhage
Authors: Roy-O’Reilly Meaghan , So Davis , Torres Glenda , Zhu Liang , Aronowski Jaroslaw , McCullough Louise D , Edwards Nancy J
Published: June 2021

Introduction:
Macrophages are the predominant cell capable of removing toxic hemoglobin at sites of tissue injury, and CD163 has been recognized as the hemoglobin scavenger receptor present on the macrophage cell surface. In this study, we explored the levels of soluble CD163 (sCD163) in patients with intracerebral hemorrhage (ICH) to ascertain whether sCD163 was associated with clinicoradiologic features and long-term functional outcomes.

Methods:
Our ICH cohort was comprised of 50 patients with moderate-sized basal ganglia hematomas. We collected serial serum and cerebrospinal fluid (CSF) at pre-specified timepoints (24 hours, 48 hours, 3-5 days, 6-8 days, and greater than 10 days post-ictus). We also obtained samples from 10 healthy controls. Levels of sCD163 were measured by enzyme-linked immunosorbent assay. A linear mixed model was used to compare sCD163 values among various groups, using a Bonferroni correction for multiple test adjustment. The method of generalized estimating equations was used to determine associations with dichotomized outcomes (modified Rankin Scale score 0-3 versus 4-6).

Results:
Compared to healthy controls, serum sCD163 was higher in the ICH patients (40.6 versus 128.4 ng/mL). Within the ICH cohort, early values (24 hours to 5 days post-ictus) of serum sCD163 were significantly higher in patients who elaborated minimal perihematomal edema (PHE) (200.3 in patients with less than 10 mL PHE versus 71.8; p = 0.046). 6 to greater than 10 days post-ictus, sCD163 levels tailed off for patients with less PHE whereas levels rose in patients with greater PHE. Continued subacute elevation of sCD163, particularly in the CSF, was highly associated with poorer outcomes, both at discharge and at 90 days (p < 0.001). These associations were independent of age, gender, peak hematoma volume, and ICH score; there was a statistically significant association of CSF sCD163 values with degree of intraventricular hemorrhage (p = 0.04).

Conclusions:
sCD163 may be a dynamic marker in ICH, with acute levels distinguishing edema patterns and subacute levels predicting functional outcome. Further studies are needed to confirm these findings and explore the pathophysiology behind these observations.
Abstract WMP109: Characterizing Brain Microstructural Changes in Childhood Arterial Ischemic Stroke Using Multi-shell Diffusion Magnetic Resonance Imaging
Authors: Yang Joseph Y , Beare Richard , Stojanovski Belinda , Maixner Wirginia J , Seal Marc L , Mackay Mark T
Published: June 2021

Introduction:
New imaging markers employing sophisticated models of tissue microstructure may lead to better understanding of neurobiological substrates in childhood arterial ischemic stroke.

Methods:
Four children with acute unilateral MCA territory ischemic stroke were retrospectively included [two males, age range 2 -16 years]. Parameters of two complementary diffusion modeling techniques: Neurite Orientation Dispersion and Density Imaging (NODDI), and Spherical Mean Technique (SMT) were estimated using two-shell diffusion data acquired at presentation (
b- values
= 1000 and 3000 s/mm
2
). For comparison, diffusion tensor imaging (DTI) parameters were also estimated. Parameter estimates were derived from the acute infarct-affected gray matter, the reconstructed pyramidal tract and the contra-hemispheric homologs. Contrast-to-noise ratios (CNRs) were calculated for each pair of homologous brain regions.

Results:
In both the acute infarct-affected gray matter, and pyramidal tracts, the multi-shell parameter estimates demonstrated increased intra-cellular volume fraction (F
icvf
and INVF in figure), predominant reduced extra-cellular microscopic diffusivity (ENMMD and ENTMD in figure), and increased orientation dispersion of the infarct-affected axonal fibers (ODI in figure). These findings were consistent with respective acute stroke histopathological features of cytotoxic edema, narrowed extracellular spaces, and axonal swelling. The CNRs were associated with stroke severity and motor function outcome at follow-up.

Conclusion:
The parameter estimates derived from multi-shell diffusion data produces robust infarct contrast, and provides histopathologically plausible imaging biomarkers representing brain microstructural changes in acute childhood stroke. Routine clinical introduction of this imaging technique requires further elucidations of its prognostic values in predicting stroke severity and/or motor outcomes.
Abstract WMP11: Joint Commission Certified Stroke Centers Treat More Severe Strokes with Faster Procedure Times Compared to Non-joint Commission Certified Stroke Centers in the Trevo Registry
Authors: Gupta Rishi , Veznedaroglu Erol , Budzik Ronald F , English Joey D , Baxter Blaise W , Bartolini Bruno M , Krajina Antonin , Sarraj Amrou , Liebeskind David S , Shields Ryan D , Xiang Bin
Published: June 2021

Introduction:
Endovascular stroke therapy has become the gold standard treatment for large vessel occlusion. The Joint Commission has certified hospitals as Comprehensive stroke centers (JCCSC) based on rigorous standards in the hopes of identifying centers of excellence. We sought to determine if JCCSC have faster door to reperfusion times compared to non-JCCSC.

Methods:
The TREVO registry is a multicenter international real world registry assessing angiographic and clinical outcomes with the Trevo device being used in the first pass. We defined a CSC as certified by the Joint Commission as of July 1, 2016. Demographic information, times within the hospital, angiographic results and clinical outcomes were analyzed between the JCCSC and non-JCCSC institutions.

Results:
A total of 507 patients (329 JCCSC, 178 non-JCCSC) have completed data in the Trevo registry to date. There are a higher proportion of patients with ASPECTS < 7 being treated at JCCSC vs. non-JCCSC (8.8% vs. 0.0%, p<0.02). There were no differences in outcomes, reperfusion rates or symptomatic hemorrhage rates between the two groups. Demographics were similar except patients treated at a JCCSC had a higher median NIHSS [17 vs. 15, p<0.003] compared to the non-JCCSC group. Median (IQR) door to puncture times did not differ between the two groups [85(57-132) vs. 91(59-137), p<0.96], but patients treated at a JCCSC had lower mean angiographic procedure times [59 ± 34 minutes vs. 66±44 minutes, p<0.05]. The analysis did not change when we looked at the subset of patients who were not transferred with anterior circulation strokes less than 8 hours from onset.

Conclusions:
Patients treated at a JCCSC had faster procedural times, without faster door to procedure times when compared to non-JCCSC centers. Outcomes were no different, due to imbalances in stroke severity at baseline and a higher proportion of patients with ASPECTS < 7 being treated.
Abstract WMP112: Safety and Efficacy of Intravenous Thrombolysis and Endovascular Therapy in Children with Acute Ischemic Stroke: A Systematic Review and Meta-analysis
Authors: Pacheco Juliana , Winzer Simon , Barlinn Jessica , Reichmann Heinz , Puetz Volker , Siepmann Timo , Barlinn Kristian
Published: June 2021

Background:
Although intravenous thrombolysis (IVT) with tissue plasminogen activator (tPA) and endovascular therapy (EVT) are considered standard-of-care treatment of acute ischemic stroke in adults, safety and efficacy of these treatment modalities in children is unknown to date. We reviewed current literature and synthesized data on safety and efficacy of IVT and EVT in children with ischemic stroke.

Methods:
We performed a systematic review and meta-analysis of all available case series and observational studies that evaluated safety of IVT and EVT in pediatric stroke patients aged less than 18 years. We searched the electronic databases Medline, PubMed, Cochrane Library, Google Scholar for eligible studies. Safety outcomes comprised any intracerebral hemorrhage post-treatment and in-hospital mortality. A random-effects model was used to compute pooled effect estimates and the
I

2

statistic was used to assess heterogeneity. Our analysis complied with PRISMA statement.

Results:
We identified 152 records through database searching, of which only 3 studies with a total of 16,335 pediatric patients with ischemic stroke met our eligibility criteria. Of these studies, two explored safety of sole IVT and one combinatory IVT/EVT. In-hospital mortality rates were similar between pediatric stroke patients treated with either IVT or IVT/EVT and controls (odds ratio=0.85, 95%CI: 0.15-4.87; p=0.857), with moderate evidence of heterogeneity (

I
2

=64%). Risk of intracerebral hemorrhage was substantially increased in children receiving IVT (odds ratio=3.60, 95%CI: 1.66-7.80; p=0.001) compared with controls, with no evidence of heterogeneity (

I
2

=0%). Efficacy of revascularization therapies could not be analyzed due to lack of uniform outcome data in the included studies.

Conclusions:
Our synthesized data analysis revealed a substantial lack of evidence for acute revascularization treatment of children with ischemic stroke. While an increased risk of intracerebral hemorrhage related to IVT emerged in our analysis, further research is needed to elaborate these findings.
Abstract WMP118: In Safe Hands: Implementation on the Stroke Unit. Does it Improve Patient Care and Ward Efficiency?
Authors: Jala Sheila M , Giaccari Sarah , Passer Melissa , Bertmar Carin , Day Susan , Krause Martin
Published: June 2021

The ‘In Safe Hands” (ISH) is a structured interdisciplinary bedside round developed to increase patients participation in their care in acute hospital wards. This has shown to improve quality of care by reducing communication errors and complications, enhancing a culture of safety in an acute hospital. The purpose of this study was to assess the effect of ISH on length of stay (LOS), in-hospital complications and assess whether the ISH enhances patient and staff satisfaction in a stroke unit of a tertiary hospital in Sydney, Australia. This was a longitudinal study pre and post implementation. A total of 200 patients participated in the study. Data on the length of stay, incidence rate relating to patient safety and patient and staff satisfaction surveys using Patient Experience Tracker (PET) devices were collected pre and post implementation. ISH increased the number of patients with at least 72hours in stroke unit care by 80 percent (P < 0.001). Fever and hyperglycaemia were treated in all patients following ISH implementation vs only 50% and 64% respectively of patients pre ISH implementation. Swallow screen was completed in all patients prior oral intake compared to 92% of patients of the pre ISH group (P = 0.03). There was no significant difference in the LOS and complications. All stroke patients received stroke education and there were no readmissions post implementation. There was no significant difference in the patient and staff satisfaction. In conclusion, although ISH did not improve the primary endpoints of LOS, complications and satisfaction it did improve protocol adherence.
Abstract WMP16: Relative Dwi Signal Intensity as a Predictor of Stroke Onset Time Compared to the Visual DWI/FLAIR Mismatch
Authors: Wouters Anke , Dupont Patrick , Christensen Sören , Lansberg Maarten G , Albers Greg W , Thijs Vincent , Lemmens Robin
Published: June 2021

Introduction:
The DWI/FLAIR mismatch has been proposed as an imaging pattern to predict stroke onset before 4.5h in patients with unknown time of symptom duration. Limitations of the DWI/FLAIR mismatch include the additional imaging time required to obtain FLAIR, difficulty of assessment in patients with severe white matter disease, poor interrater agreement, and motion sensitivity of longer MRI sequences. We hypothesised that automated analysis of DWI imaging would be at least as accurate to predict stroke onset before 4.5h.

Methods:
Data from the Axis 2 trial were used and patients were included in whom a DWI lesion was detected by automated software (RAPID). The visual DWI/FLAIR mismatch was rated in accordance with the criteria of the ongoing WAKE-UP trial. For every patient the relative DWI (rDWI) was calculated in a voxel based manner as the ratio of the diffusion intensity in that voxel and the median diffusion intensity of a sphere with radius 15 mm around the homologue voxel in the contralateral hemisphere. The mean and standard deviation (SD) of the rDWI was obtained in the DWI lesion. Receiver operating curves (ROC) and corresponding area under the curves (AUC) for predicting the 4.5h time-window were determined.

Results:
We included 200 patients. In 8 patients (4%) the visual DWI/FLAIR rating was hampered due to either extensive white matter disease or poor quality of FLAIR imaging. The DWI/FLAIR mismatch had an AUC of 0.66 to predict stroke onset before 4.5h vs an AUC of 0.71 for rDWI SD (p for difference=0.4). The optimal rDWI SD threshold for predicting stroke ≤ 4.5h was 0.23. Using this threshold, stroke onset was accurately predicted in 73% of patients vs 65% accuracy with the visual DWI/FLAIR mismatch (p for difference=0.1). (table 1)

Conclusion:
Our results suggest that rDWI may have advantages over the visual DWI/FLAIR mismatch for predicting the time of stroke onset. rDWI provides an accurate and objective assessment with the potential for fully automated processing.
Abstract WMP19: Identifying in vivo Luminal Thrombus Within 72 Hours After Stroke Onset: Interim Results of the Stroke Imaging Package Study
Authors: Xu Wei-hai , Chen Huisheng , Yang Yi , Xu Jun , Zhang Meng , Lu Baoquan , Wu Shiwen , You Yong , Zhou Zhangyu , Hu Hongtao , Fang Le , Lu Zhengqi , Lou Min , Song Haiqing , Li Mingli , Huang Yining
Published: June 2021

Background:
The presence of luminal thrombus is associated with a high risk of stroke recurrence. Using high-resolution magnetic resonance imaging(HRMRI) and susceptibility-weighted imaging(SWI), luminal thrombus can be identified in vivo. We aimed to investigate the occurrence of luminal thrombus in patients with acute ischemic stroke.

Methods:
Patients with first ever stroke within 72 hours from onset, confirmed by diffusion weighted imaging, were recruited from 16 medical centers. Conventional MRI, magnetic resonance angiography, HRMRI (including 3-dimentional T1 images and 2-dimentional T2 images), and SWI were performed. Luminal thrombus was identified if isointense/hyperintense signals on 3-dimentional T1 images of HRMRI or susceptibility vessel sign on SWI were observed within the course of intracranial arteries.

Results:
Six hundred and one patients (70% male, mean age 61±16 years old, mean NIHSS 6± 5) were enrolled. Among them, 112 patients underwent recanalization therapies. Median time from symptom onset to MRI was 44 ± 20 hours. Luminal thrombus was identified in 138 (23%)patients. The occurrence rate of luminal thrombus was non-significantly different between the patients treated with and without recanalization therapies(16% vs.25%, p=0.054). Symptomatic luminal thrombus was more likely observed in large artery atherosclerosis stroke(121/240,50%) and cardicac stroke(11/36,31%) than other stroke subtypes (0/288 in lacunar stroke, 0/6 in stroke of undetermined etiology and 1/31 in cryptogenic stroke, P<0.001). There were five patients with asymptomatic luminal thrombus irrelevant to ischemic lesions.

Conclusions:
Luminal thrombus is common in patients with acute ischemic stroke within 72 hours from onset. Further studies are required to clarify whether in vivo thrombus imaging can predict early stroke recurrence.
Abstract WMP2: Trevo 2000: Real-World Experience in the First 1247 Patients
Authors: Binning Mandy J , Budzik Ronald F , Baxter Blaise W , Bartolini Bruno M , Liebeskind David S , Krajina Antonin , English Joey D , Maxwell Christina , Veznedaroglu Erol
Published: June 2021

Objective:
The Trevo Registry is designed to assess real world outcomes of the Trevo Retriever in patients experiencing ischemic stroke. This is the largest prospective study for acute stroke intervention, with 1247 patients currently enrolled and 90 day outcomes in 1021 patients. The primary endpoint is revascularization status based on post-procedure TICI score and secondary endpoints include 90-day mRS, 90-day mortality, neurological deterioration at 24 hours and device/procedure related adverse events.

Methods:
The study is a prospective, open-label, consecutive enrollment, multi-center, international registry of patients undergoing mechanical thrombectomy for acute stroke using the Trevo stent retriever as the initial device. Enrollment is expected to reach 2000 subjects at up to 100 sites.

Results:
As of August 13, 2016 a total of 1247 patients were enrolled. The median NIHSS at admission was 16 (IQR 11-20). Most patients (66.2%) were treated at >/= 6 hours from last known normal with a median procedure time of 50 minutes (32-77). The occlusion site was M1 or M2 in 74.5%. General anesthesia was employed in 46.6% of procedures. TICI 2b or 3 revascularization was 92.8% with an average of 1.6 passes with the device. Median NIHSS at 24 hours and discharge was 6 and 4 respectively. Fifty-five percent of patients had mRS ≤2 at 3 months and the overall mortality rate was 15.4%. Patients treated after 8 hours of symptom onset had a 94.9% revascularization rate and 52.8% mRS ≤2 at 3 months. The symptomatic ICH rate was 1.2%. Patients who met the revised AHA criteria for thrombectomy were found to have 58.4% mRS 0-2 at 90 days.

Conclusions:
The Trevo Retriever Registry represents the first real world data with stent retriever use in the era of clinical trials showing the overwhelming benefit of stent retrievers to treat acute ischemic stroke. Due to the fact that this data represents real world use of the Trevo Retriever, (e.g. subjects pre-stroke mRS >1 (16.5%) and those treated 6-24 hours after stroke symptoms (33.8%), this data cannot be compared to the results from recent trials with restricted eligibility criteria. Future subgroup analysis of this large cohort will help to identify areas of future research to enhance outcomes further with this treatment modality.
Abstract WMP39: Indispensable Role of CCR5 Signaling In Tregs Protection Against Early Blood Brain Barrier Disruption After Stroke
Authors: Li Peiying , Wang Long , Hu Xiaoming , Chen Jun
Published: June 2021

Background and purpose:
Our previous study found adoptively transferred regulatory T cell (Treg) protected against ischemic stroke via attenuating blood brain barrier (BBB) disruption. Here, we examined the role of CCR5, a chemokine receptor in the Tregs’ recruitment and protection to the ischemic BBB after stroke.

Methods:
Transient focal cerebral ischemia was induced in widetype C57/BL6 or CCR5(-/-) mice by unilateral middle cerebral artery occlusion (MCAO) for 60 minutes. Tregs (2x10
6
/mouse) in 200 μl PBS or PBS control were injected intravenously at 2 hours after MCAO. Chemo-attractant migration of Tregs to the ischemic BBB was examined by two photon in vivo imaging and cell migration test in vitro. RT-PCR, Immunofluorescence staining and confocal microscopy were used to assess the chemokine expression, endothelial ICAM-1 expression and peripheral immune cell infiltration following cerebral ischemic injury. In vivo endogenous IgG leakage and in vitro BBB integrity were examined to determine the important role of CCR5 in Tregs’ protection on the ischemic BBB.

Results:
We found that cerebral ischemia reduced Treg number in the peripheral but the expression of CCR5 on Tregs in the blood was increased. In the ischemic brain, the expression of CCR5 ligands were significantly upregulated, and the expression of CCL5 co-localized with ischemic brain endothelial cells. Genetic depletion of CCR5 on the donor Tregs significantly impaired the transferred Tregs’ ability to migrate to the ischemic BBB and attenuated Tregs’ protection against BBB disruption and peripheral immune cell infiltration as determined by two photon in vivo imaging, immunofluorescence staining and MMP-9 ELISA. In vitro migration test further revealed that depletion of CCR5 hindered Tregs to migrate across endothelial cell layer.

Conclusions:
In conclusion, CCR5 plays an indispensible role in Tregs’ recruitment and protection against ischemic BBB disruption. Therapeutic strategies targeting CCR5 warrants further investigation to improve Treg based cell therapy in stroke treatment.
Abstract WMP41: Neuronal Sirt1 is Required for Resveratrol Preconditioning Induced Ischemic Tolerance
Authors: Koronowski Kevin B , Saul Isa , Balmuth-Loris Zachary , Perez-Pinzon Miguel
Published: June 2021

Introduction:
Our previous work demonstrates that resveratrol, a naturally occurring polyphenol, protects against cerebral ischemia when administered 2 or 14 days prior to injury. Resveratrol activates Sirt1, an NAD
+
-dependent deacylase that regulates cellular metabolism. It has been postulated that neuronal Sirt1 directly mediates this neuroprotection but it remains to be empirically tested.

Objective:
The objective of this study was to generate an inducible, neuronal-specific Sirt1 knockout mouse and determine whether neuronal Sirt1 is necessary for resveratrol-induced ischemic tolerance.

Methods:
Twenty to twenty-five gram neuronal-specific Sirt1 knockout mice (Sirt1neu-/-) and WTs were induced with tamoxifen. Mice were randomized for 1) western blot; 2) resveratrol preconditioning (RPC; 10 mg/kg resveratrol i.p.) or vehicle (1.5% DMSO; 0.9% saline) treatment 2 days prior to 60 minute middle cerebral artery occlusion (MCAo); 3) untargeted primary metabolomics by GC-TOF-MS; or 4) transcription factor activation profiling. Twenty-four hours following MCAo, neurological score was used to assess functional outcome and infarct volume was quantified by TTC staining.

Results:
Tamoxifen treatment removed WT Sirt1 protein from major brain regions but not from heart (Figure 1A, n=3). In WT, RPC reduced infarct volume by 43.7% and improved neurological score by nearly 3 points, however these effects were lost in Sirt1neu-/- (Figure 1B, n=5-9). Compared to WT, metabolic profiles from Sirt1neu-/- displayed significantly altered glycolysis metabolites (Figure 1C, n=8). Activation of hypoxia inducible factor (HIF) was reduced by 48% in Sirt1neu-/- (Figure 1D, n=3).

Conclusions:
We generated and utilized an inducible, neuronal-specific knockout mouse to demonstrate that neuronal Sirt1 specifically is required for RPC-induced ischemic tolerance. Additionally, Sirt1 regulates glycolysis in the brain, possibly through its interaction with HIF.
Abstract WMP42: Neuro and Gliogenesis in a Nonhuman Primate Model of Ischemic Stroke with Impaired Dexterous Movements
Authors: Choudhury Gourav , Daadi Marcel
Published: June 2021

Ischemic stroke is the leading cause of upper extremity motor impairments. Well-characterized experimental stroke models for upper extremity motor impairment remain underdeveloped. Cortical representation of dexterous movements in nonhuman primates (NHP) is functionally and topographically similar to that in humans. We recently reported the characterization of an NHP model of focal ischemia reperfusion with a defined syndrome, impaired arm function and finger dexterity. In this study, we investigated the cellular changes in the neural stem cell compartment and glial cell populations in this NHP model.

NHPs were subjected to transient cerebral ischemia by temporarily occluding the M3 segment of the left side middle cerebral artery (MCA). Motor and cognitive functions following the stroke were evaluated using the object retrieval task with barrier-detour. Postmortem analysis included magnetic resonance imaging (MRI) and immunohistopathology to map the infarct and characterize the neurogenic and gliogenic changes.

The MCA occlusion produced significant loss of fine motor function characterized by impaired dexterity. Immunocytochemical analysis revealed significant increase of Sox2+ neural stem cells in the subventricular zone, and of GFAP+ astrocytes (P<0.0001) and Iba-1+ microglia (P<0.0001) in the infarct region. In addition, there was a 42% increase in doublecortin positive cells (P<0.0001) compared to non-ischemic hemisphere.

This study describes the cellular composition of the endogenous changes in the neural stem cell compartment and in the stroke region. These data may help reveal the cellular identity mediating neural plasticity and the cellular mechanisms mediating behavioral deficits and post-stroke recovery.
Abstract WMP47: Robot-assisted Mechanical Therapy Protects Against Stroke-induced Skeletal Muscle Injury
Authors: Balch Maria H , Sen Chandan K , Khanna Savita , Harris Hallie , Gnyawali Surya , Rink Cameron L
Published: June 2021

Introduction:
A growing body of literature supports acute changes to skeletal muscle physiology in response to stroke-induced central nervous system injury. While stroke survivors depend on rehabilitation to facilitate functional recovery, study of post-stroke rehabilitation and mechanisms of recovery remains limited. The current work addresses development of a Robot-Assisted Mechanical Therapy (RAMT) device and facilitation of reproducible, objective analysis of post-stroke rehabilitation. We hypothesize that RAMT permits systematic study of post-stroke mechano-physiotherapy and restores hindlimb function after stroke by protecting against skeletal muscle injury.

Methods:
Wistar rats (male, N=26) were subjected to middle cerebral artery occlusion (MCAO), after which they received daily RAMT (RAMT+; 0.5N force, 1Hz frequency, 10mm linear motion over medial stroke-affected gastrocnemius) or none (RAMT-; anesthesia only) for 14 days. Assessment of gait, sensorimotor behavior, and muscle perfusion quantified effects of RAMT on post-stroke function, while skeletal muscle analysis (RT-PCR, immunohistochemistry) evaluated expression of myostatin, a molecular target of stroke.

Results:
Compared to RAMT- controls, RAMT+ rats benefited from higher perfusion in stroke-affected gastrocnemius (47.7%, p<0.05). RAMT+ improved post-stroke gait and sensorimotor behavior, evidenced by better track width (11.9%, p<0.05), less time in quad support (54.4%, p<0.05), greater travel distance (60.5%, p<0.05), and more time mobile (41.7%, p<0.05). Additionally, RAMT+ protected from post-stroke induction of myostatin, decreasing mRNA and protein expression (39.1% and 88.6% respectively, p<0.05).

Conclusion:
RAMT facilitates reproducible, objective, pre-clinical study of post-stroke mechano-physiotherapy. RAMT successfully improves muscle perfusion, rescues gait deficits, preserves sensorimotor behavior, and attenuates the stroke-induced rise in myostatin. Ongoing efforts focus to characterize the mechano-sensitive miRNA transcriptome in skeletal muscle and employ electrophysiology to quantitatively map post-stroke neuroplasticity in response to RAMT.
Abstract WMP54: Association Between Arterial Stiffness and All-cause Mortality Among Stroke Survivors in the United States
Authors: Lin Michelle P , Ovbiagele Bruce , Gottesman Rebecca F , Sanossian Nerses , Markovic Daniela , Towfighi Amytis
Published: June 2021

Introduction:
Indirect measures of arterial stiffness such as wide pulse-pressure, high BP variability, elevated LDL, and abnormal ankle-brachial index (ABI) each predict cerebrovascular events and outcomes; however, less is known about the utility of these markers in combination.

Hypothesis:
Higher number of abnormal indirect measurements of arterial stiffness is associated with higher mortality after stroke.

Methods:
Using the US National Health and Nutrition Examination Surveys 1999-2004 (with linked mortality through 2010), we assessed arterial stiffness scores for adults aged ≥40 years. Arterial stiffness score (range 0-4) was defined as number of positive findings among the following: high SBP variability (highest quartile), wide pulse pressure (highest quartile), abnormal ABI (<0.9 or >1.3), or LDL ≥ 100 mg/dL. We assessed stroke prevalence across arterial stiffness scores. Independent relationships between arterial stiffness score and all-cause-mortality were assessed using Cox regression models.

Results:
Among 6,711 individuals, 25% were aged ≥ 65 years, 51% were women, and 79% were White. Factors associated with higher arterial stiffness scores were: older age, female sex, lower education, and lower socioeconomic status (all P<0.001). Higher arterial stiffness score was associated with higher odds of stroke (OR 3.3, 95% CI 1.9-5.5). Of the score components, stroke survivors were more likely to have wide pulse pressure and abnormal ABI compared to those without stroke (P<0.001). There was a dose-dependent relationship between arterial stiffness score and all-cause mortality after stroke: adjusted mortality rate ratios were 1.0. 1.9, 3.1, 3.4 across increasing arterial stiffness scores (trend p=0.0039). Mortality curves are shown.

Conclusions:
Simultaneous assessment of common ambulatory markers for arterial stiffness provides a simple, readily available scheme for stroke risk outcome stratification.
Abstract WMP55: Risk Factors and Composite Risk Score for Predicting Stroke After Sepsis
Authors: Shao Yuefan , Kulick Erin , Kamel Hooman , Elkind Mitchell , Boehme Amelia K
Published: June 2021

Background and Purpose:
Sepsis has been identified as a risk factor for stroke, however, the underlying mechanisms remain unclear and risk factors that may predispose a patient to an increased stroke risk post-sepsis are unknown. The study aims to identify risk factors associated with post-sepsis stroke and subsets of the population that are most vulnerable to stroke after sepsis.

Methods:
The 2007 - 2009 California State Inpatient Database from the Health Care Utilization Project (HCUP) was used. Patients who were over the age of 18 and hospitalized with sepsis, defined by ICD-9 codes, were included. Patients who died during their sepsis hospitalization were excluded. The outcome of interest was a primary diagnosis of stroke, including ischemic and hemorrhagic, as defined through ICD-9 codes. Associations between risk factors and stroke were analyzed using multivariable logistic regression. A composite risk score was generated to assess the accuracy of prediction among the post-sepsis population.

Results:
Of the 114679 patients with diagnosis of sepsis, 0.5% (N=572) had a primary diagnosis of stroke within a year of their sepsis hospitalization. Significant predictors for stroke are listed in Table 1. A score was generated from these risk factors with points assigned based on beta coefficients. The ROC for the score is 0.6840. As the composite score increases, the risk of stroke increases (OR=1.46, 95% CI 1.40-1.53 for each point increase in the score). Post-sepsis patients with a score greater than or equal to 1 (N=35773) have the highest prevalence (prevalence = 31.19%) and are more likely to have a stroke. (OR= 3.18, 95% CI 2.69, 3.76)

Conclusion:
Independent risk factors for stroke after sepsis include valvular diseases, congestive heart failure, coagulopathy, lymphoma, peripheral vascular diseases, pulmonary circulation disorders, and renal failure.
Abstract WMP56: Increase in Rate of Utilization of Withdrawal of Care in Acute Ischemic Stroke Patients in USA
Authors: Adil Malik M , Zweifler Richard
Published: June 2021

Background:
Early deaths are common in stroke, and most occur as a result of brain death or withdrawal of care when prognosis for recovery is believed to be poor. Survivors of severe stroke often have a gradual improvement in function but may experience significant disability, all of which may benefit from skilled palliative care. The objective of this study was to determine the rate of withdrawal of care in patients with ischemic stroke (IS) who underwent different treatment plans.

Methods:
We determined the frequency of “withdrawal of care” among patients with IS who received thrombolysis only, endovascular treatment only, both thrombolysis and endovascular treatment and neither thrombolysis nor endovascular treatment. We used Nationwide Inpatient Survey data files from 2006 -2011.

Results:
The annual rates of “withdrawal of care” increased from 0.9% in 2006 to 5.5% in 2011, p=<0.0001 in IS patients treated with thrombolysis. The annual rates of “withdrawal of care” increased from 2.8% in 2006 to 9.0% in 2011, p=0.0006 in IS patients who underwent endovascular treatment. The annual rates of “withdrawal of care” increased from 2.0% in 2006 to 10.3% in 2011, p=0.0009 in IS patients treated with thrombolysis and endovascular treatment. The annual rates of “withdrawal of care” increased from 0.8% in 2006 to 3.0% in 2011, p=<0.0001 in IS patients who neither received thrombolysis nor underwent endovascular treatment.

Conclusions:
We found a considerable increase in rate of withdrawal of care with aggressive treatment, which may be due to disease severity and/or patient/family preference. Prognostic models and clinical experience for severe stroke patients may be biased by frequent withdrawal of care, leading to errors in prognostication with significant consequences including premature withdrawal of care, suboptimal outcomes and higher risk of short-term mortality.
Abstract WMP57: Declining Blood Pressure is Associated with Subcortical Microinfarcts in Older Adults
Authors: Raman Mekala R , Graff-Radford Jonathan , Przybelski Scott A , Lesnick Timothy G , Mielke Michelle M , Roberts Rosebud O , Boeve Bradley F , Knopman David S , Petersen Ronald C , Parisi Joseph E , Dickson Dennis W , Jack Clifford R , Kantarci Kejal
Published: June 2021

Hypertension is highly prevalent in the elderly population and microinfarcts are the most common vascular brain pathology identified in older adults at autopsy. We investigated the associations between systolic and diastolic blood pressures measured antemortem and the presence of microinfarcts at autopsy. Study subjects (n=302; age range=71-95) were participants in the population-based Mayo Clinic Study of Aging autopsy study, who had blood pressure measurements recorded during life. We investigated both cross-sectional systolic and diastolic blood pressure measurements at the baseline visit and the change in blood pressure (slope). Presence and location (subcortical or cortical) of chronic microinfarcts was abstracted from the autopsy reports. Of the 302 study subjects, 47 (16%) had cerebral microinfarcts, and, of those, 18 (38%) had subcortical microinfarcts and 29 (62%) had only cortical microinfarcts. The baseline blood pressures were not different between subjects with no microinfarcts, subcortical microinfarcts, and only cortical microinfarcts. In a logistic regression model including time between last blood pressure measurement and death, a greater decline in systolic [OR= 1.06 (1.01, 1.11); p=0.02]) and greater decline in diastolic [OR= 1.11 (1.02, 1.20); p=0.01] blood pressures were predictors of the presence of subcortical microinfarcts at autopsy. However, these variables were not associated with the presence of cortical microinfarcts. In conclusion, microinfarcts are common in the older adult population, and most of them are located in the cortex. A greater decline in both systolic and diastolic blood pressures and their association with subcortical microinfarcts, but not with cortical microinfarcts, may have implications for aggressive lowering of blood pressure in the elderly population.
Abstract WMP6: Treatment Effect of 3D Stent Retriever with Aspiration and Aspiration Alone in Acute Ischemic Stroke
Authors: Nogueira Raul , Frei Donald , Soulimani Ghita , Kuo Sophia S , Buell Hope , Mualem Elan , Barraza Leticia , Bose Arani , Sit Siu Po , Siddiqui Adnan ,   for the Penumbra 3D Investigators
Published: June 2021

Introduction:
A recent meta-analysis of five stroke endovascular therapy (EVT) randomized controlled trials (RCTs) confirmed EVT’s benefits in patients with acute ischemic stroke caused by proximal large vessel occlusion (LVO).

Hypothesis:
We hypothesize that treatment with the novel 3D Stent Retriever used with the Penumbra System and the Penumbra System alone could confer similar benefits in this stroke cohort.

Methods:
The Penumbra 3D trial was a RCT to compare the safety and efficacy of the 3D Stent Retriever when used in conjunction with the Penumbra Aspiration System (3D/PS) versus the PS alone. Inclusion criteria for the 3D RCT included presentation within 8 hours of symptom onset, NIH Stroke Scale ≥ 8, and refractory to or not eligible for IV rtPA. Analysis compared 90-day mRS 0-2 vs the EVT RCT meta-analysis reported by the HERMES collaboration (Goyal et al.,
Lancet
2016).

Results:
A total of 172 of 198 enrolled patients met analysis criteria. Baseline NIHSS, ASPECTS, and age were similar between the 3D RCT and HERMES control. Successful reperfusion (mTICI 2b-3) occurred in 74.1% of PS alone (63/85) and 83.9% of 3D/PS (73/87) cases. When both arms were pooled, 79.1% (136/172) of cases achieved successful reperfusion. Results on 90-day functional independence showed both 3D cohorts and the pooled results of the trial had significantly higher rates compared to the HERMES control (IV rtPA).

Conclusions:
Both the 3D/PS and the PS devices alone showed benefit compared to IV rtPA monotherapy from a recent EVT RCT meta-analysis.
Abstract WMP62: PR Interval Prolongation and Cryptogenic Stroke: A Multicenter Retrospective Study
Authors: Montalvo Mayra J , Tadi Prasanna , Merkler Alexander , Gialdini Gino , Martin-Schild Sheryl , Navalkele Digvijaya , Samai Alyana , Nouh Amre , Hussain Mohammad , Goldblatt Steven , Hemendinger Morgan , Chu Antony , Song Christopher , Kamel Hooman , Furie Karen L , Yaghi Shadi
Published: June 2021

Background:
Atrial dysfunction or “cardiopathy” has been recently proposed as a mechanism in cryptogenic stroke. A prolonged PR interval may reflect impaired atrial conduction and thus may be a useful biomarker of atrial cardiopathy. We aim to compare the prevalence of PR interval prolongation in patients with cryptogenic stroke (CS) when compared to known non-cryptogenic non-cardioembolic stroke (NCNCS) subtypes.

Methods:
We retrospectively analyzed prospective ischemic stroke databases and included consecutive patients between December 1
st
, 2013 and August 31
st
, 2015 in three comprehensive stroke centers (Rhode Island Hospital, Hartford Hospital, and Tulane University Medical Center). Consecutive patients 18 years or older with a discharge diagnosis of ischemic non-cardioembolic stroke were included. The main outcome was ischemic stroke subtype (CS vs. NCNCS). We compared PR intervals as a continuous and categorical variable (< 200 ms; ≥ 200 ms) and other clinical and demographic factors between the two groups and used multivariate regression analyses including age and other factors deemed significant on univariate analyses to determine the association between PR interval prolongation and CS.

Results:
We identified 644 patients with ischemic non-cardioembolic stroke (224 CS and 420 NCNCS). The PR interval was longer in patients with CS vs NCNCS (175.4 ± 35.2 ms vs. 166.5 ± 27.7 p = 0.005). After adjusting for factors that were found to be significant in univariate analyses, a prolonged PR interval was independently associated with CS (Odds Ratio: 1.70; 95% CI 1.08-2.70; p=0.022). The association was more pronounced when excluding patients on atrio-ventricular nodal blocking agents (OR=2.64, 95% CI 1.44-4.83, p=0.002).

Conclusions:
A prolonged PR interval is associated with CS and may be a biomarker of atrial cardiopathy in patients with cryptogenic stroke. This association needs to be confirmed in prospective neuro-epidemiological cohorts.
Abstract WMP67: Thrombogenic Effect of FFAs in Cardioembolic Stroke
Authors: Seo Woo-Keun , Seo Jin-Man , Oh Kyungmi
Published: June 2021

Objective:
Four decades ago, free fatty acids (FFA) were proved to enhance thrombus-formation. Recently, the role of FFA in thromboembolism has reemerged in the context of cardioembolic stroke. Therefore, we attempted to determine the role of FFA on the embolic risk in various potential sources of cardioembolism (PSCE) with the hypothesis that, if elevated FFA levels in stroke patients are associated with thrombogenesis, patients with a well-known high risk of embolic sources would have high FFA levels.

Methods:
Data collected from two hospital-based stroke registries were analyzed to investigate the association between FFA and PSCE.

Results:
A total of 2770 acute stroke patients, including 539 with cardioembolic stroke, were selected for analysis. FFA was an independent predictor for cardioembolism (OR 2.755, 95% CI 2.221-3.417,
P
<0.001) and significantly associated with fibrinogen and prothrombin time. Among the PSCE, atrial fibrillation, valvular heart disease, congestive heart failure with low ejection fraction, left atrial thrombus, left ventricular thrombus, left atrial smoke, and ventricular wall motion abnormality were independently associated with FFA. FFA level increased with the number of PSCE per patient. Significant correlation between the FFA ratio of PSCE to non-PSCE and the annualized thromboembolic event rate of each PSCE from the literature was noted (
r
2
=0.5829,
P
<0.001).

Conclusions:
Among acute stroke patients, FFA levels increase in proportion to the increase in thromboembolic risk for each PSCE. These results imply that enhanced thrombogenicity could be the main mechanism to explain the elevated FFA levels in patients with cardioembolic stroke.
Abstract WMP7: Intra-arterial Therapy and Post Treatment Infarct Volumes in the Revascat Randomized Controlled Trial
Authors: Al-Ajlan Fahad S , Menon Bijoy K , de Miquel Maria A , Millan Monica , San Roman Luis , Demchuk Andrew M , Jovin Tudor , Davalos Antoni , Goyal Mayank
Published: June 2021

Background and Purpose:
To find out if the beneficial effect of endovascular treatment (EVT) on functional outcome could be explained by a reduction in post treatment infarct volume in the REVASCAT multi-center randomized controlled trial.

Methods:
The REVASCAT trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 206 enrolled subjects (EVT n=103; control n=103), post treatment infarct volume was measured in 204 subjects. Post treatment infarct volumes were compared by treatment assignment and recanalization status. Appropriate statistical models were used to assess relationship between baseline clinical and imaging variables, post treatment infarct volume and functional status at 90 days [modified Rankin Scale (mRS)].

Results:
Median post treatment infarct volume in all subjects was 23.7 ml (IQR 9.3-78.2 ml), in the EVT arm (16.3 ml, IQR 8.3-58.5 ml) and in the control arm (38.6 ml, IQR 11.9-86.8 ml) (p<0.02). Median post treatment infarct volume in the EVT arm in recanalizers was 14.6 ml (IQR 7.8-46.2 ml) vs. 92.9 ml (IQR 14.6-233.1 ml) in the non-recanalizers (p=0.05). Median post treatment infarct volume in the control arm in recanalizers was 18.1 ml (IQR 8.4-76.7 ml) vs. 92.9 ml (IQR 14.6-233.1 ml) in the non-recanalizers (p=0.02). Post treatment infarct volume (p<0.001) and recanalization status (p<0.01) were the only independent predictors of 90 day mRS; all baseline variables lost their relevance in this model.

Conclusion:
Endovascular therapy in the REVASCAT trial was associated with a significant reduction in infarct volume. Recanalization status and post treatment infarct volume best predict 90-day clinical outcomes.