bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3600: A Critical Analysis of Intra-arterial Thrombolytic Doses in Acute Ischemic Stroke Patients.
Authors: Hassan Ameer , Rostambeigi Nassir , Grigoryan Mikayel , Chaudhry Saqib A , Hassan Summer , Cordina Steve , Khatri Rakesh , Qureshi Adnan I
Published: March 2022

Background:
Intra-arterial (IA) recombinant tissue plasminogen activator (IV rt-PA, Alteplase), Tenecteplase, and Retplase are currently used in patients with acute ischemic stroke, the relationship between IA dose and hemorrhage rates, clinical outcomes and radiographic outcomes have not been rigorously studied.

Objective:
We evaluated the safety and recanalization efficacy associated with various doses of intra-arterial thrombolytics for treating acute ischemic stroke patients.

Methods:
Consecutive patients with acute ischemic stroke who underwent emergent endovascular treatment over seven years from our prospectively maintained database were included. Univariate and multivariate analyses were performed to determine the dose response relationship between thrombolytic doses and outcomes. For standardization we used a conversion of newer thrombolytics to establish a standard dosage throughout cases (10mg alteplase = 2 Units of Reteplase = 6.3 Units of Tenectaplase). Patient characteristics and outcomes were analyzed including age, weight, risk factors, use of intravenous rt-PA,and use of additional mechanical thrombolysis. The rates of intracerebral hemorrhage (ICH) and favorable clinical outcomes (discharge modified Rankin score (mRS) = 0-2) were analyzed with various doses after adjusting for potential confounders.

Results:
There were 290 patients [male 52% (n=150)] who received endovascular treatment for acute ischemic stroke, of those 210 (72%) were treated with IA rt-PA or equivalent thrombolytics with doses up to 69 mg of alteplase. There were 115 patients (40%) [men 46% (n=53)] who received both IV and IA therapy. Mean±SD IA tPA dose was 10±9 mg (range: 1.5-69mg) and total IA+IV tPA dose 85±21 mg (range: 43-149mg). Neither the dose of IA tPA nor total tPA dose (IV+IA) was associated with favorable outcomes or ICH (p=NS). Mean IA tPA dose was no different between the patients with and without ICH [9.9 versus 9.8, p=0.4]. Adjusting for age, admission NIHSS score, and IA tPA/equavalent dose, the use of combined mechanical and thrombolytic IA therapy was associated with higher ICH rate (OR=4, p=0.004) but not with favorable outcomes (p=0.2) compared to thrombolytic therapy alone. Multivariate analysis showed administration of IV rt-PA significantly improved favorable outcomes compared to IA therapy alone (OR=1.8, p=0.04) with no increased risk of hemorrhage (p=NS).

Conclusion:
Our study demonstrates that IA rt-PA or equivalent thromboytics in doses up to 69 mg are safe without any evidence of dose related adverse events even in those patients who had received IV rt-PA prior to procedure presumably due to the short-half life of rt-PA.
Abstract 3615: Degree of CTA Collaterals determines the Early and Final MRI DWI Lesion Volumes in Endovascular Treatment of Acute Ischemic Stroke
Authors: Wisco Dolora , Uchino Ken , Gebel James , Ching-Cheng Esteban , Alam Shazia , Aoki Junya , Tateishi Yohei , Jin Yongming , Spiotta Alex , Hussain Muhammad S
Published: March 2022

Background:
Large pre-treatment DWI lesion volumes have been correlated with poor response to intra-arterial (IA) stroke therapies. In patients with large intracranial vessel occlusion, the degree of collateral vessel seen on CT Angiography (CTA) has also been correlated with patient outcomes. However, the relationship between the degree of collaterals on CTA and DWI lesion volume early on and after intervention has not been described and may be useful in patient selection for acute therapies.

Objectives:
To assess the relationship of CTA collaterals and DWI lesion volumes in patients eligible for IA stroke therapy, and to assess pre-treatment CTA collaterals with final infarct volume in patients receiving IA therapy for acute stroke.

Methods:
Single tertiary center retrospective review of patients considered for IA stroke therapy from May 2010 to June 2011. CTA collaterals were assessed as 0 - no collaterals, 1 - minimal collaterals (<50% of affected territory), 2- partial collaterals (> 50% of affected territory), and 3 - full collaterals. DWI volumes on initial MRI scans and post-treatment MRI scans (done 24-96 hours) were calculated by region of interest analysis. Univariate and multivariate analyses were performed (STATA, College Station, TX)

Results:
71 patients were available for analysis. Acute CTA imaging revealed no collaterals in 6 patients, minimal collaterals in 5 patients, partial collaterals in 33 patients and full collaterals in 27 patients. Baseline NIHSS correlated inversely with the degree of collaterals: In patients with no collaterals the median NIHSS was 20.5 (IQR 11.5 - 25.5), with minimal collaterals 18 (IQR 14-23.5), and with partial or full collaterals 13 (IQR 10-17). Initial DWI lesion volume correlated well in an inverse fashion with CTA collaterals as follows: none or minimal collaterals 88.7cc (intraquartile range (IQR) 51.6cc - 177.43cc), partial 19.7cc (IQR 13.7cc - 36.9cc) and full collaterals 9.7cc (IQR 4.7cc - 29.6cc). Final DWI lesion volumes also inversely correlated as follows: none 152.0cc (IQR 76.0cc - 204.4cc), minimal 118.8cc (IQR 57.5cc - 141.1cc), partial 34.9cc (IQR 14.2cc - 107.4cc), and full 17.2cc (IQR 8.6cc - 47.9cc). On multivariate analysis, baseline NIHSS and CTA collaterals were significantly correlated with DWI lesion volume of > 80cc (P<0.05)

Conclusion:
The degree of CTA collaterals are significantly inversely correlated with DWI lesion volumes before and after IA therapy for acute stroke
Abstract 3630: Function-Blocking Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Antibody Injection is Neuroprotective after Focal Cerebral Ischemia
Authors: Weston Gillian K , Liu Fudong , Moore Craig , McCullough Louise D
Published: March 2022

Introduction:
Extracellular metalloproteinase inducer, EMMPRIN, is a cell surface glycoprotein found on endothelial cells and astrocytes and has a key role in the expression of MMPs. It was reported that EMMPRIN expression is upregulated in a mouse model of permanent cerebral ischemia and that EMMPRIN co-localized with MMP-9 in infarcted tissue. There is evidence to support that elevation of MMP activity contributes to injury after stroke and that inhibition of MMPs can reduce infarct volume in rats. In this study we hypothesized that inhibition of EMMPRIN with a function-blocking antibody would reduce infarct volume and improve stroke outcome in mice subjected to a MCAO stroke through reduction in MMP activation.

Methods:
Transient 90-minute middle cerebral artery occlusion (MCAO) was performed on male wild-type mice treated with vehicle, rat IgG2a (eBioscience), or with function blocking anti-EMMPRIN antibody (eBioscience) injected via tail vein. A single injection was given at stroke onset. Mice were sacrificed at 48 hours post reperfusion. Brains were harvested for TTC staining (n=4/group; significance p<0.05). A second cohort of vehicle and drug treated mice (n=3 vehicle, n=7 drug) were subjected to transient 90-minute middle cerebral artery occlusion and were sacrificed at 72 hours. These mice were given the initial dose at stroke onset and an additional dose at 48 hours. Both cohorts were subjected to behavioral analysis using a modified 4 point scoring system.

Results:
Mice treated with the function blocking EMMPRIN antibody had smaller infarct volumes when compared with vehicle treated animals. This reduction in damaged tissue was consistent in the cortex, striatum and total hemisphere of each group. Drug treated mice had improved behavior scores when compared to vehicle treated mice at both the 48hr and 72hrs time points. Furthermore, vehicle treated mice had higher mortality rates (20% at 48hrs and 66% at 72hrs) than drug mice (0% at 48hrs and 14% at 72hrs) at both time points.

Discussion:
Animals treated with a function-blocking antibody to EMMPRIN presented with less infarct volume and better behavior scores than similar animals treated with vehicle. Thus, EMMPRIN inhibition is neuroprotective. Considering monoclonal antibody therapy has been successful in the treatment of other diseases, this data suggests that inhibition of EMMPRIN via administration of an antibody could have therapeutic potential for stroke patients.
Abstract 3643: Intimal Hyperplasia Of Leptomeningeal Arteries In CADASIL
Authors: Dong Hairong , Blaivas Mila , Wang Michael
Published: March 2022

Objective:
CADASIL is associated with abnormalities of penetrating white matter arteries; but recent studies showing pathology in the gray matter and the increased incidence of migraine with aura suggest that leptomeningeal vessels may be affected in the disease. The pathology of leptomeningeal vessels has not been extensively characterized. This study tests the hypothesis that the intima and media of leptomeningeal small vessels are abnormal in CADASIL compared to age matched controls and the very old.

Methods:
Samples analyzed included four genetically proven CADASIL brains (average age 61), four controls without symptoms of cerebrovascular disease (average age 68), and five very aged brains (average age 90). Temporal lobe brain sections (approximately 5-10 cm
2
) from autopsy material were stained with Movat’s pentachrome and immunohistochemistry (for smooth muscle actin, NOTCH3, and collagen). All leptomeningeal arteries < 150 um were digitally imaged (total number 190 [CADASIL], 171 [control], and 157 [aged]). We measured intimal, medial, and adventitial thickness, inner and outer diameter, and sclerotic index (SI).

Results:
We first confirmed that pentachrome staining precisely delineates the intima, media, and adventitia of leptomeningeal arteries by comparing serial vessels stained using immunohistochemical markers. Pentachrome stained was then used to delineate three layers of each vessel. The intima of CADASIL arteries was significantly thickened compared to controls and the very aged (7.5+/-3.2; 1.3+/- 0.5; 1.85+/-0.69 um;
p
<0.0001). Medial thickness was lower in CADASIL compared to controls (but similar to the very aged) (3.5+/-3.2; 5.3+/-2.6; 3.3+/-2.6 um;
p
<0.0001). Inner diameters of CADASIL vessels were larger than controls and the very aged (41+/-21; 34+/-19; 33+/-17 um;
p
<0.005). Outer diameters of CADASIL vessels were larger than controls and the aged (75+/-33; 54+/-28; 55+/-25 um;
p
<0.0001). SI was significantly increased in CADASIL compared to other groups (0.46+/-0.12; 0.38+/-0.10; 0.41+/-0.10;
p
<0.05).

Conclusion:
The leptomeningeal arteries in CADASIL undergo significant remodeling. The most obvious change is a dramatic increase in intimal thickness and vessel diameter. The significant loss of media in CADASIL was also seen in very aged brains. These pathological findings may underlie migraine with aura, which is seen at a higher frequency in CADASIL patients. In addition, leptomeningeal pathology could contribute to impairment of cerebral blood flow regulation in the white matter.
Abstract 3658: Early and Late Predictors of Hyperthermia after Spontaneous ICH: on behalf of VISTA Collaborators
Authors: Rincon Fred , Lyden Patrick , Mayer Stephan
Published: March 2022

Introduction.
Hyperthermia is an independent predictor of poor outcome after stroke. We sought to determine early predictors of hyperthermia after spontaneous ICH.

Methods.
Data of patients from acute ICH trials registered in the Virtual International Stroke Trials Archive (VISTA-ICH) were analyzed. Admission variables were assessed in relation to the recorded temperatures at baseline, 24hr, 48hr, 72hr and 7-days, using linear regression based on the normal distribution of the dependent variables. Models were fitted and odds ratios (OR) and 95% confidence intervals (CI) were calculated.

Results.
In total, 303 patients were included in the analysis. The average age of the cohort was 66 ± 12 years, 200 (66%) were males, the median admission NIHSS was 13 (Interquartile range [IQR], 9-18), median GCS was 15 (IQR, 14-15), mean temperature was 36.4 ± 0.5 °C at baseline; 36.7 ± 0.6 °C at 24hr; 37.1 ± 0.7 °C at 48hr; 36.9 ± 0.6 °C at 72hr, and 36.8 ± 0.6 °C at 7-days. The median hematoma volume at baseline CT scan was 15cc (IQR, 8-33), intraventricular hemorrhage (IVH) was present in 104 (34%) of patients, and hematoma growth >33% occurred in 50 patients (34%, n=185). Variables associated with higher temperature were: admission NIHSS >13, IVH, infratentorial origin or location, volume of hematoma growth, hematoma growth >33%, and the following additional components of ICH score: base volume >30ml, and Glasgow Coma Scale (GCS) <13. After adjustment, ICH baseline volume >30cc (OR, 1.2; 95%CI, 1.1-1.3) and hematoma growth >33% (OR, 1.1; 95%CI, 1.01-1.2) (Baseline intercept = 37.2 C) were associated with hyperthermia at 24hrs; and hematoma growth >33% (OR, 1.1; 95%CI, 1.02-1.2) and IVH (OR, 1.1; 95%CI, 1.02-1.2) (Baseline intercept = 37.1 C) were associated with higher temperature at 7-days.

Conclusions.
These data suggests that in ICH patients, hematoma baseline volume >30cc and hematoma growth are independently associated with higher temperature at 24 hrs and hematoma growth and IVH with higher temperature at 7 days. Prevention of hematoma growth and treatment of IVH may decrease the prevalence of hyperthermia in these patients.
Abstract 3661: Implementing a Mobility Team in a Primary Stroke Center: A Pilot Program
Authors: Donnelly Rose M , Ford Adrienne , Brem Stephanie , Hutchinson Michael , Tranor Tim , Griffin Julie
Published: March 2022

Background:
Literature review has shown that in an ICU setting, the use of a mobility team decreased both the ICU and hospital stay. Patients also experienced improved functional status, strength and an improved sense of well being. Many patients appear more empowered and more involved in their care when they are moving. There was no current literature available regarding the use of a mobility team with the acute stroke patient population in an inpatient setting.

Purpose:
The purpose of this pilot program was to evaluate the impact of a dedicated mobility team in an acute neuroscience setting on mobility levels, fall rates, patient satisfaction and discharge disposition.

Methods:
This pilot was implemented in a Primary Stroke Center within a large tertiary medical center. This facility admits 1200-1300 stroke patients annually. A RN-Patient Care Technician mobility team was available from 0830-1700, Monday-Friday, rotating on three neuroscience divisions. Patients with orders for chair and ambulation were mobilized per the team. If on bedrest, range of motion and turning was provided. The team attempted to round on all patients twice per day. All activities completed with patients were documented in the electronic medical record. Outcomes were analyzed in aggregate.

Results:
The mobility team was piloted for a 90 day period ending May 20, 2011. Of the eligible patients, 83% received mobility interventions. Patient testing and patient refusal were the top reasons an intervention was not provided. Mobility levels demonstrated an increase in ambulation of 22%. Falls decreased 37%. Patient satisfaction scores increased up to 19%. An increase in discharges to home with outpatient therapies and a subsequent decrease in inpatient rehabilitation were observed.

Conclusions:
In conclusion these results demonstrate the positive impact of the mobility team on patient mobility, falls, patient satisfaction and discharge disposition. The mobility team continues to be used with ongoing data collection to evaluate ongoing outcomes.
Abstract 3667: Institution of a Telemedicine for Acute Stroke Protocol in a Major Metropolitan Setting to Decrease iv-tPA Administration Times
Authors: Fanale Chris , Ruiz Lisa , Whaley Michelle , Salottolo Kristin
Published: March 2022

Introduction:
Telemedicine for Acute Stroke Evaluation and Treatment has been widely used for providing expert stroke neurology advice for patients presenting to rural hospitals. Iv-TPA administration rates in these experiences are high (20-25%). However, national iv-tPA administration rates still are below this level. In addition, less than 30% of patients are receiving iv-tPA in less than 60 minutes. We describe a novel telemedicine network that augments existing on-call neurological support to decrease door to needle times for iv-tPA administration.

Methods:
Data from 6 metropolitan hospitals in the Denver area were collected to assess rapidity of iv-tPA administration for Acute Ischemic Stroke. All hospitals had existing acute stroke protocols, on-call board certified neurologists, board certified Emergency Room Physicians (EDP) available on a 24/7 basis. Stroke Program leaders including Emergency Room Physicians, Neurologists, and administrators from these hospitals were invited to participate in an initiative to decrease door to needle times. Through this committee, consensus was reached that the arrival of a neurologist be less than 15 minutes from arrival of the patient to the Emergency Room. At times and places where this could not be achieved by physical presence, telemedicine technology was employed. This Telemedicine Intiative (TI) was instituted on May 1st, 2011. Time data regarding patient arrival, time to CT scan, time in CT scan, arrival of neurologist, first Emergency Room physician evaluation, tPA administration will be tracked.

Results:
Prior to institution of the Telemedicine Initiative, average door to needle times for the six hospital network was 86 minutes. In the first month of institution of TI, average door to needle times decreased to 67 minutes across the network. 102 telemedicine consultations have been performed to date. All telemedicine consultations were instituted within 10 minutes of arrival of the patients to the emergency room.

Conclusions:
Employing Telemedicine in a metropolitan hospital setting with exisiting neurological coverage, acute stroke protocols and board certified ED Physicians may decrease the time needed to administer iv-TPA in acute ischemic stroke patients.
Abstract 3671: Intra-Carotid Mesenchymal Stem Cell Therapy is Superior to Intravenous delivery in Rat Model of Cerebral Ischemia
Authors: Yavagal Dileep R , Lewis Natashia , Lin Baowan , Garza Philip , Giannini Alessandra , Amatangelo Steven , Pham Tienlong , McNiece Ian , Raval Ami P , Hare Joshua
Published: March 2022

INTRODUCTION:
There are multiple pre-clinical studies showing significant neurological functional benefit of Mesenchymal Stem Cells (MSCs) in cerebral ischemia. MSCs are adult bone marrow derived cells that have a high potential for clinical translation. The optimal route of MSC delivery has not been established. Intra-carotid (IC) delivery via catheters has several attributes attractive for clinical application & may be superior to intravenous (IV) delivery as it circumvents systemic trapping of cells and allows more cells to reach the target lesion. In our previous study using the rat rMCAo model, we found the maximum tolerated dose (MTD) of IC MSCs to be 1 x 10^5 HYPOTHESIS: We tested the hypothesis that the MTD of IC mesenchymal stem cells (MSCs) is more efficacious as compared to IV MSCs and IC control. We further hypothesized that the MTD of IC MSCs given at 24 hours is more efficacious as compared to IC MSCs at 60 minutes. METHODS: 34 female Sprague-Dawley rats underwent 90 minutes reversible middle cerebral artery occlusion (rMCAo). At 60 minutes or 24 hours post rMCAo, rats were assigned to receive: allogeneic IC MSCs at a dose of 1x 10^5 or IC phosphate buffered saline (PBS) 0.5ml or allogeneic intravenous (IV) MSCs 1 x 10^6 & rMCAo with no treatment (sham). Primary outcome measures were blinded neurodeficit score and infarct volume at 4 weeks.

RESULTS:
At 24 hours post rMCAo, there was no significant difference in the neurodeficit score (NDS) amongst the groups. At four weeks post treatment, the IC MSC group showed a significantly lower NDS (7%_3.3) as compared to IV MSCs (10.2%_1.5, p=0.042); In subgroup analysis, IC MSCs given at 60 minutes showed no significant difference compared to other groups, but IC MSC given at 24 hours showed a significantly lower neurodeficit score (5.8 %_2.6) as compared to IC PBS (10.8%_1.2, p=0.003), IV MSCs (10.2 %_1.5, p=0.005) and Sham (10%_ 3.4, p=0.018) (
Fig1
.). The mean infarct volume of the group treated with IC MSCs was significantly lower as compared to IC PBS (18cc%_ 8 vs. 50cc%_17, p=0.043). On infarct topography frequency map comparison, we found a significantly decreased volume of infarction in the cortical regions in IC MSC group as compared to IC PBS group.

CONCLUSIONS:
Treatment with maximum tolerated IC MSC dose of 1 x 10^5 post rMCAO results in superior functional outcome when compared with IV MSC 1 x 10^6, IC PBS and sham rats. Additionally, IC MSC at 24 hours is more efficacious than IC MSC at 60 minutes. There is also a significant decrease in infarct volume in IC MSC treated rats when compared with IC PBS. The IC MSCs may ameliorate injury in the cortex surrounding the core.
Abstract 3676: MyD88-Dependent Pathway Has a Dual Effect on Brain Injury after Cerebral Ischemia/Reperfusion in Mouse
Authors: Hua Fang , Wang Jun , Ishrat Tauheed , Prunty Megan C , Atif Fahim , Sayeed Iqbal , Gewirtz Andrew T , Stein Donald G
Published: March 2022

Myeloid differentiation primary-response protein-88 (MyD88) is one of the intracellular adaptors in Toll-like receptor (TLR) signaling pathways, which regulates the activation of nuclear factor kappa B (NF-kappa-B) and transcription of other proinflammatory cytokines. We assessed the hypothesis that MyD88-dependent signaling mediates the inflammatory responses in ischemic brain and is implicated in the process of brain injury. A mouse model of cerebral ischemia/reperfusion (I/R) was induced by transient middle cerebral artery occlusion (tMCAO). MyD88 knockout (KO) mice and wild type control mice (WT, C57BL/6J) were assigned to I/R or sham-operated groups. The mice were killed at 4 hrs or 24 hrs after reperfusion following 60 minutes of MCAO. Using Nissl staining, brain infarct areas were evaluated and expressed as a percentage of the whole brain. Brain edema was evaluated and presented as the percentage of water content in the total weight of the brain tissue. The expression of mRNA was detected by real-time PCR, and the levels of inflammatory cytokines were measured by ELISA and Western Blots. The infarct size was analyzed by t-test. Brain edema and inflammatory response were analyzed by one way ANOVA with post hoc comparisons. Our results showed that the brain infarct size was not significantly different in MyD88KO mice compared with WT mice 24 hrs after cerebral I/R. However, brain edema (water content) significantly increased in MyD88KO mice compared with WT 24 hrs after ischemia (p<0.05). The data also showed that the levels of mRNA of CD14, Pellino-1, cyclooxygenase-2 (COX-2), and Interferon beta-1 (INFb1) increased significantly 4 hrs after cerebral I/R in WT mice compared to sham-operated controls (p<0.05). MyD88 deficiency inhibited the increased expression of Pellino-1 (p<0.05) and COX-2 (p<0.05), but not CD14. Twenty-four hrs after cerebral I/R, the protein levels of Interleukin
-
1-beta, Interleukin
-
6 (IL-6), p-IkappaB alpha, and the activity of NFkappaB, significantly increased in the ischemic brain in WT mice, and were inhibited in MyD88KO mice. Interestingly, VEGF significantly increased in MyD88KO mice compared with WT mice (p<0.05). In addition, ZO-1, a tight-junction protein on the blood-brain barrier (BBB) decreased in MyD88KO mice compared with WT mice subjected to cerebral I/R. Our data demonstrates that MyD88 contributes to the activation of inflammatory responses after cerebral I/R. However, MyD88 reduces brain edema by mediating the expression of VEGF, and tight-junction proteins, which are important for maintaining BBB integrity. We concluded that the MyD88-dependent pathway has a dual effect on brain injury induced by cerebral I/R. Interpreting the results for the role of MyD88 dependent pathway based on brain injury from whole animal experiments is cautioned.
Abstract 3678: Decreased Incidence of Cerebral Aneurysm Rupture with the use of Aspirin in an Animal Model
Authors: Kung David K , Tada Yoshiteru , Wada Kosuke , Liang Elena , Smietana Janel , Hasan David M. , Hashimoto Tomoki
Published: March 2022

Introduction:
A growing amount of literature in both human and animal models supports the hypothesis that chronic inflammation is a key component in cerebral aneurysm (CA) development and rupture. Aspirin has a well-documented history of safety and pharmacologic studies reveal that aspirin’s anti-inflammatory properties impede several pathways that are implicated in aneurysm growth and rupture. Recently, our secondary analysis of the International Study of Unruptured Intracranial Aneurysms showed a significant association between aspirin use and decreased incidence of subarachnoid hemorrhage. We aimed to determine whether an animal model could be used to investigate the mechanisms of aspirin’s protective effects and to refine the molecular targets for prevention of CA rupture. As an initial step, we tested whether aspirin could reduce the incidence of aneurysmal rupture in our mouse CA model.

Method:
We generated CAs by a combination of induced hypertension and local elastic lamina disruption. In male C57/B6 mice, systemic hypertension was induced by desoxycorticosterone acetate-salt treatment. Elastase (35mU) was injected stereotaxically in the right basal cistern to produce disruption of elastic lamina. One week after aneurysm induction surgery, mice were given 30mg/kg daily aspirin by gavage. Control animals were given the same volume of water. Aneurysmal rupture were detected by daily clinical evaluation and confirmed by brain dissection. All animals were sacrificed three weeks after elastase injection to determine rate of CA formation.

Results:
For the control group (N=10), 80% developed CA by 3 weeks. 40% of the control animals had ruptured aneurysm that caused neurological deficits prior the end of the study. Similarly for the aspirin group (N=10), 80% developed CA by 3 weeks. However, only 20% of the animals who received daily aspirin developed cerebral aneurysm rupture.

Conclusion:
Similar to our previous human epidemiological study, we observed a strong trend of lower rate of CA rupture with daily aspirin use in our animal model. Further investigations to confirm this finding and studies on the mechanistic basis of aspirin’s protective effect are underway. Using this animal model with established rates of CA development and rupture allows us to test other anti-inflammatory agents and conduct studies on specific molecular targets for the prevention of aneurysm rupture.
Abstract 3689: Safety And Efficacy Of Anticoagulation In Patients With Cerebral Venous Sinus Thrombosis Presenting With Subarachnoid Hemorrhage.
Authors: Calleja Juan , Reyes Maricela , Huesca Karina , Gonzalez Paulina , Arauz Antonio
Published: March 2022

Objective:
Conventional treatment of cerebral venous sinus thrombosis (CVST) has been systemic heparinization. A small percentage of CVST present with subarachnoid hemorrhage (SAH). We retrospectively evaluated the efficacy and safety of anticoagulation in consecutive patients with SAH due to CSVT.

Materials and Methods:
A retrospective review of our stroke database from November, 1994 to August, 2010 identified 21 consecutive patients who had presented with SAH secondary to CVST. CVST was documented through angiography, venous angioTC or venous phase angioresonance. CVST was documented through CT scan or lumbar puncture when image was equivocal. Diagnosis was performed by a neurologist and confirmed by neuorradiologists. Patient histories were reviewed to collect data on presentation, presence of venous infarction or hemorrhagic transformation, affected sinus, treatment with anticoagulation, follow up, and functional outcome.

Results:
21 patients were included for analysis. The mean patient age was 39years (20-83). Sixty-seven percent of patients were female. The initial symptom was thunderclap headache in 11 patients (52%), acute progressive headache in 9 patients (43%) and seizures in 1 patient (5%). 15 patients (71.4%) were treated with anticoagulants. 10 patients (48%) were treated with low molecular weight heparin, 5 patients (24%) with non fractioned heparin. All these patients continued treatment with oral anticoagulation. 3 patients (14.3% received treatment with antiplatelet agents. 3 patients (14%) received no treatment. No patients developed intracaranial or extracranial hemorrhagic complications after initial treatment. One patient died due to cerebral edema. All other patients had good functional outcome (modified Rankin Scale<2) regardless of treatment.

Conclusion:
Treatment with anticoagulant drug appear to be safe in the setting of CVST related HSA. Outcome appears to be good in most patients. Our study is not powered to detect the efficacy of treatment in these patients.
Abstract 37: Tracking Endothelial Injury And Platelet Activation In Childhood Cerebral Arteriopathy
Authors: Eleftheriou Despina , Ganesan Vijeya , Hong Ying , Klein Nigel , Brogan Paul
Published: March 2022

Background:
Cerebral arteriopathy is a well established risk factor for childhood arterial ischaemic stroke (AIS) recurrence. However, risk stratification of children with AIS and cerebral arteriopathy based on underlying disease mechanisms is currently impossible thus complicating the development of targeted secondary prevention strategies.

Objective:
We hypothesized that persistent cerebrovascular endothelial injury confers an increased prothrombotic tendency central to the pathogenesis of arteriopathy progression and stroke recurrence. The aim of this single centre cross-sectional study study was to relate indices of endothelial injury and thrombotic propensity to radiological and clinical disease course at least 6 months after the index AIS.

Methods:
Circulating endothelial cells (CECs) and microparticles (MPs) were identified with immunomagnetic bead extraction and flow cytometry respectively. MP mediated thrombin generation was assessed using a fluorogenic assay. Results were expressed as median and range.

Results:
51 children with AIS aged 8•8 (0•9-17•4) years and 20 paediatric controls were included. Eleven were categorised as having progressive disease on clinical and/or radiological grounds while 40 had non-progressive disease. CECs were significantly raised at 120 (66-732) cells /ml in the progressive group, compared to 24 (0-88) cells/ml in the non-progressive group (p = 0•0002) and 32 (0-84) cells/ml in controls (p= 0•0003). In 2/8 children studied prospectively AIS recurrence was associated with increased CECs at 186 (140-232) cells/ml. Total circulating annexin V+ MPs were significantly higher at 553 (136- 1616) x 10 3/ml in then progressive compared to the non-progressive group 227 (49-893) x 10 3/ml, p=0•003. MPs were of endothelial, neutrophil and platelet origin and expressed tissue factor. MP-mediated thrombin generation was enhanced with peak thrombin generation of 127•3 (30-215) nM in the progressive compared to the non-progressive disease group 25 (10-73•40) nM, p=0•0001.

Conclusion:
We provide important insights into the role of endothelial injury, platelet activation and thrombogenicity in childhood AIS that could for the first time lead to stratified, mechanism specific secondary stroke prevention strategies.
Abstract 3707: Minocycline Treatment Inhibits Spontaneous Hemorrhage in a Mouse Model of Cerebral Amyloid Angiopathy
Authors: Yan Ping , Zhu Alec , Xiao Qingli , Kraft Andrew , Lee Jin-Moo
Published: March 2022

Background:
Cerebral amyloid angiopathy (CAA), the accumulation of amyloid around arterioles, is a common cause of recurrent intracerebral hemorrhage (ICH) in the elderly. The precise mechanism leading to ICH is unclear, but several mouse models which mimic aspects of CAA have been created. These mice develop amyloid plaques, CAA, and microhemorrhages with advanced age. We have utilized one such mouse model (Tg2576 mice) to determine if inhibiting inflammatory responses with minocycline may impact spontaneous hemorrhage rates.

Methods:
Groups of aged-matched tg2576 mice, ranging from 15-20 months, were treated with saline (n=8) or minocycline 50 mg/kg (n=9), ip every other day for 2 months. After treatment, mice were sacrificed, brains were removed, sectioned and stained for amyloid (congo red and Abeta immunostaining), microhemorrhage (Perl’s Blue), astrogliosis (GFAP immunostaining), or microgliosis (CD11b immunostaining). CAA load and amyloid plaque load were measured based on area fraction of 4 regularly spaced brain sections from each mouse. Hemorrhages were counted and graded based on size (grade 1, 1-3 Perl’s blue puncta; grade 2, 4-10 puncta; grade 3, >10 puncta) in 30 regularly spaced brain sections from each mouse. Groups were compared using Student’s t-test or Mann-Whitney Rank Sum Test.

Results:
Mice tolerated minocycline treatment without adverse effects: average weights before, during, and after treatment did not differ between groups. Mice treated with minocylcine had significantly fewer hemorrhages than saline-treated mice (0.26 vs 0.43 hemorrhages/section, p=0.02). Grade 2 hemorrhages were significantly fewer in minocycline-treated mice (0.06 vs. 0.17 hemorrhages/section, p=0.005), but grade 1 and 3 hemorrhages were not statistically different between groups. Amyloid plaque load in the cortex (14 vs 13% area) and hippocampus (11 vs 8% area) did not differ between the two treatment groups. Total brain CAA load (0.12 vs 0.14% area) was also unchanged. Immunohistochemical analysis revealed far fewer activated microglia (CD11b immunostaining) in the minocycline-treated group compared to the saline-treated group, especially around amyloid deposits (both plaques and vascular amyloid); astrocytosis (GFAP immunostaining) was not altered.

Conclusions:
These data indicate that minocycline treatment reduced spontaneous hemorrhage rates in Tg2576 mice, a murine model of CAA and AD, without affecting amyloid load. Thus, it appears to inhibit downstream mechanisms involved in CAA-induced hemorrhage by decreasing microglial activation. Because minocycline is FDA-approved for a variety of clinical uses, its safety has been well-documented. A clinical trial using minocycline in CAA patients with ICH should be considered.
Abstract 3741: Spokes or Hubs: A Better Milieu for Acute Ischemic Stroke Intervention Trials?
Authors: Papesh Nancy D , Hui Ferdinand , Gebel James
Published: March 2022

Background:
The evolution of acute ischemic stroke (AIS) treatment networks has yielded many so-called spoke and hub networks, where patients may present to hospitals that possess stroke expertise, but perhaps not the full range of treatment options such as those present at so-called hubs. Presentation patterns at spokes and hubs may differ in terms of demographics, severity, and in terms of presentation time, which may yield opportunities to target specific AIS therapy subgroups.

Hypothesis:
We hypothesized that patients present earlier to stroke ready regional community hospitals than the centrally located main campus and therefore provide greater potential opportunity for acute stroke intervention.

Methods:
The Cleveland Clinic Health System Stroke network is comprised of a quaternary main campus and 10 regional hospitals. There are two regional hospital tertiary stroke treatment hubs, located geographically east and west of the main campus. AIS time data were reviewed at each of these three centers, not including the other [n] primary stroke centers in the system spanning 2008 through the first half of 2011. Time from last known well to hospital presentation was calculated for each patient, patients with missing time data were excluded, yielding a total of 2269 consecutive patients. Presentation times were then graphed, and patterns analyzed.

Conclusions:
The time data queried suggests that AIS patients arrive earlier in their course at the two regional centers by a large margin. Therefore, a higher percentage of total presenting patients may be eligible for acute stroke intervention and trials. The pattern of presentation times may or may not be unusual to that of the Cleveland Clinic system, but such variation in patient presentation patterns may suggest more efficient avenues of trial recruitment. Clinical research integrated throughout a stroke hospital system would likely yield better quality and quantity patient recruitment.
Abstract 3750: Embolus Adhesion to Activated Endothelium After Embolization: A Parameter To Predict Outcomes Of Mechanical Thrombectomy In Acute Ischemic Stroke
Authors: Chueh Juyu , Kuhn Anna Luisa , Mehra Manik , Feula Giancarlo , Wakhloo Ajay K , Gounis Matthew J
Published: March 2022

Background:
In the MERCI trial and a prior animal study (Catch device), it was reported that when the thrombus retrieval maneuver was performed, the deployed device failed to mobilize the thrombus. Increased pulling force was applied and resulted in device rupture. These experiences lead us to hypothesize that the occlusive mass interacts with the activated endothelium, and the stability of the embolus on the vessel wall is related to the outcomes of mechanical thrombectomy. The aim of this study is to establish a methodology to quantitatively characterize the embolus-vessel wall adhesion.

Methods:
A rabbit CCA stenosis model was developed for creation of embolic occlusion with allogeneic clot. To evaluate the morphology of the embolus analogue (EA)-endothelium interface, two occluded vessel segments were explanted at 5-hour for Martius Scarlet Blue (MSB) staining and double immunofluorescence labeling for glycoprotein (GP) IIb/IIIa and fibrin. A modified test rig with a carbon steel wire (0.6 mm in diameter) fixture was used to detach the EA from the vessel wall (n=4). The wire moved down at the test speed of 0.1mm/s. The mean force was recorded and the energy to dislodge the EA from the vessel wall was calculated by numerical integration of the force versus distance curve below. Data were presented as mean±standard error.

Results:
MSB results showed that, the EA conformed to the shape of the underlying tunica intima and the undulated internal elastic lamina tended to flatten out after the occlusion. Immunofluorescent staining showed that GP IIb/IIIa (red) co-localized with fibrin(green), mainly observed at the EA-endothelium interface (yellow) (
Fig 1
A). In the detachment tests, a test distance of 6.07±1.18 mm was achieved after imposing 422.9±113.1 gram-force*cm of energy (
Fig 1
B). The mean force was 73.08±8.5 gram-force.

Conclusions:
Presence of GP IIb/IIIa and fibrin immunoreactivity indicates the interactions between border of the EA and the luminal surface, and this finding is supported by the quantitative adhesion force acquired during the detachment test. This project is ongoing to investigate thrombus-vessel wall interactions caused by acute thrombosis. The fibrin crosslink number and the platelet volume will be characterized by using confocal laser scanning microscope, and correlated with the adhesion results.
Abstract 3771: Does Mixing T-pa At Bedside Improve DTN, Without Increasing The Risk Of Complications
Authors: Lugtu James P , Camp Debbie , Valadi Nojan , Zimmerman Susan , Anda Kim , Westbrook Trish , Burkhalter Misty
Published: March 2022

Background/issues:
Acute Ischemic stroke is a time sensitive disease. The only approved treatment is t-PA. Prior studies have demonstrated faster Door-to-Needle (DTN) times for t-PA treated stroke patients were associated with fewer complications and lower risk adjusted mortality. In conjunction to these findings the American Stroke Association has adopted in 2011 the goal to decrease the door to needle time on all eligible patients. The Georgia Stroke Professional Alliance (GA-SPA) has continued to encourage its members to achieve Target:Stroke designation. In response to this challenge seven separate facilities were able to reach this goal. Of note each facility is unique in its geographical location, size, and setting. Despite these differences each was able to obtain the same result in meeting the Target:Stroke criteria. In an effort to reduce the DTN, some facilities have begun mixing t-PA at bedside, while others utilize central pharmacy.

Purpose:
Identify the method utilized at each facility to mix t-PA. Determine if mixing at Bedside versus central pharmacy improves DTN times. Determine if mixing at bedside increases the risk of adverse affects such as sICH or increase length of stay.

Methods:
Of the Seven Target:Stroke facilities six submitted data on all t-pa recipients from January 2010 to December 2010. Each facility identified where t-PA is mixed and by whom. Facilities also provided the number of complications resulting from t-PA. Complications included increased length of stay directly related to t-pa, and sICH with an increase of two or more on the National Institute of Health Stroke Scale.

Results:
Two hundred seventeen
(
217) t-PA cases were reviewed. Four facilities mix t-PA in Pharmacy representing 115 cases with a total of three reported complications. Two facilities mix t-PA at bedside by a trained RN with a total of three reported complications. There was no statistically significant increase in complications by facilities mixing at bedside.

Conclusions:
Complications did not increase when t-PA is mixed outside of pharmacy. Facilities can successfully attain Target:Stroke Designation, regardless of where t-pa is mixed. Further studies will be conducted to see if mixing at bedside decreases DTN time.
Abstract 3776: Apixaban Compared To Aspirin In Patients With Atrial Fibrillation And Prior Transient Ischemic Attack Or Stroke: Results Of A Predefined Subgroup Analysis From Averroes
Authors: DIENER HANS-CHRISTOPH , Eikelboom John , Hart Robert G , Connolly Stuart J
Published: March 2022

Background
In patients with atrial fibrillation (AF), vitamin K antagonists (VKA) effectively prevent stroke. However many patients are unsuitable for or unwilling to take VKAs despite a high risk of stroke. Apixaban, a novel factor Xa inhibitor, is effective and well tolerated in these patients.

Methods
In AVERROES 5.599 patients with AF, at increased risk of stroke and unsuitable for VKA therapy were randomized to receive, double-blind, apixaban 5 mg twice daily or aspirin (81-324 mg/day). The mean duration of follow up was 1.1 years. The primary outcome was stroke or systemic embolism. A pre-specified subgroup analysis was performed to compare patients with and without prior TIA or ischemic stroke (
NCT00496769
).

Results
In 764 patients with prior TIA or stroke there were 10 primary outcome events in those randomized to apixaban (2.46%/year) and 33 in those randomized to aspirin (8.27%/year), hazard ratio (HR) =0.29, 95% confidence interval (95% CI) 0.15-0.60; p<0.001)(p for interaction = 0.83) . There were 9 ischemic strokes in those randomized to apixaban (2.21%/year) and 27 in those randomized to aspirin (6.27%/year), hazard ratio (HR) =0.33, (95% CI) 0.15-0.69; p<0.002)(p for interaction = 0.64). Haemorrhagic stroke occurred in one patient on apixaban and 4 patients on aspirin. Mortality rates were 22 (5.30%/year) on apixaban and 27 (6.55%/year on aspirin, (HR=0.82, 95%CI 0.47-1.45; p= 0.50)(p value for interaction = 0.11). There were no statistically significant differences in major bleeds.

Conclusions
In patients with AF who had a TIA or stroke and unsuitable for VKA therapy, apixaban reduced the risk of stroke or systemic embolism to larger extent than aspirin.
Abstract 3780: MR Imaging Of The Intracranial Vessel Wall In Paediatric Stroke
Authors: Dlamini Nomazulu , Yau Ivanna , Shroff Manohar , Elbers Jorina , Askalan Rand , deVeber Gabrielle , Macgregor Daune , Mikulis David , Moharir Mahendranath
Published: March 2022

Background
Arteriopathy in childhood arterial ischaemic stroke (AIS) is common and is postulated to be a predictor of outcome. The distinction between inflammatory (transient cerebral arteriopathy [TCA], CNS angiitis) and non-inflammatory (arterial dissection, moyamoya) arteriopathies is vital to guide acute management decisions. Currently available non-invasive angiographic imaging techniques are inadequate to reliably distinguish inflammatory from non-inflammatory causes. Conventional catheter angiography, the gold standard, is invasive and not always feasible.

Objective:
To report the findings of a novel non-invasive arterial wall MR imaging technique in three children with arterial ischemic stroke due to arteriopathy.

Method:
3-Tesla T1-weighted 2D FLAIR fast spin echo sequence (slice thickness 3mm, matrix size 512x512) in plane and perpendicular to the vessel of interest were performed in three children with AIS before and after intravenous administration of Gadolinium, in addition to routine sequences.

Results:
The first child had TCA (
Fig. 1
), the second had arterial dissection and the third had CNS angiitis (see
table
).

Conclusion:
Our series highlights the utility of a novel non-invasive MR imaging technique of vessel wall as distinct patterns of vessel wall enhancement could be demonstrated in children with TCA, arterial dissection and CNS angiitis. Prospective studies are required to further assess the diagnostic utility of vessel wall enhancement in children with arteriopathy-related AIS. This would also help us understand the pathophysiologic mechanism of this finding.

Table 1. y=years; F=female; M=male; dICA=distal internal carotid artery; BA=basilar artery
Abstract 3781: Harm Avoidance: A Novel Risk Factor for Cerebral Infarction
Authors: Wilson Robert S , Boyle Patricia A , Levine Steven R , Yu Lei , Hoganson George M , Buchman Aron S , Schneidner Julie A , Bennett David A
Published: March 2022

BACKGROUND:
Harm avoidance, a trait indicative of behavioral inhibition, is associated with disability and dementia in old age, but the basis of these associations is uncertain.

OBJECTIVE:
To test the hypothesis that higher level of harm avoidance is associated with increased risk of cerebral infarction.

METHODS:
Longitudinal clinical-pathologic cohort study. Subjects were from the Rush Memory and Aging Project. As part of this longitudinal study, 1,082 older persons without dementia completed a standard measure of harm avoidance: the 35-item Harm Avoidance Scale from Cloninger’s Temperament and Character Inventory. During a mean of 3.5 years of follow-up, 258 individuals died of whom 206 (80%) underwent brain autopsy, the results of which are currently available in 192. Main Outcome Measures: Number of chronic gross and microscopic cerebral infarctions (each expressed as 0,1, or >1) identified on a uniform neuropathologic examination. RESULTS: Trait scores ranged from 0 to 32 and were approximately normally distributed (mean 11.6 ± 7.0 SD). On postmortem examination, chronic microscopic infarction was found in 45 (28 with 1, 17 with >1) and chronic gross infarction was found in 66 (31 with 1, 35 with > 1). In a Bivariate Dale Model adjusted for age, sex, and education, higher harm avoidance was associated with higher likelihood of both microscopic (estimate = -0.08, SE = 0.02, p = 0.002) and gross (estimate = -0.06, SE = 0.02, p = 0.011) cerebral infarction. A high level of the trait (score=17, 75th percentile) was associated with an approximate doubling of the likelihood of each type of infarction (2.4- fold increase for microscopic, 1.8-fold increase for gross) compared to a low level of the trait (score = 6, 25th percentile). These associations persisted in subsequent models that controlled for cognitive and motor function, cardiovascular risk factors and conditions, or neuroticism, and it was stronger for subcortical than cortical infarction.

CONCLUSIONS:
Higher level of the harm avoidance trait may be a risk factor for cerebral infarction, both gross and microscopic. The mechanism appears independent of known cardiovascular risk factors and warrants further study.