bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP76: Investigation of the Influence of Coil Configuration on Cerebral Aneurysm Fluid Dynamics Using a Novel Finite Element Approach
Authors: Babiker Haithem , Gonzalez L. Fernando , Chong Brian , Frakes David H
Published: July 2021

INTRODUCTION:
Despite more than a decade of endovascular coil treatment, the effects of coils on cerebral aneurysm (CA) hemodynamics are still poorly understood. Coils present several challenges to in vivo and in vitro flow measurement techniques and previous in silico methods have suffered from large assumptions on coil geometry. Here we present the first fluid dynamic simulations of coiled CAs that consider the structure and deployment mechanics of embolic coils. We also investigate the influence of coil packing density, design, and configuration on CA fluid dynamics.

Methods:
Coil deployment was modeled using a novel finite element approach that realistically simulates coil dynamics during deployment. Two coil designs were investigated: helical and 3D. Coil design and material properties were matched to manufacturer specifications. Five deployment sequences of each coil design, at different microcatheter placements, were simulated in two idealized CA models with variable neck sizes. Blood flow was simulated using computational fluid dynamics. Simulated deployments and fluid dynamics were then compared to deployments of actual coils in identical physical CA models and in vitro particle image velocimetry flow measurements.

Results:
Simulated results closely matched in vitro data. Reductions in aneurysmal velocity magnitudes were largest for 3D coils and in a narrow-neck model. In that model, 3D coil deployments reduced average aneurysmal velocity magnitudes by a 51% - 69% range at packing densities less than 20% and by a 74% - 84% range at packing densities greater than 30%. Linear regression results showed reductions were strongly dependent on the spacing between coil loops within the aneurysm and packing density, with correlations of 0.6 and 0.7 respectively.

Conclusion:
Coil design and packing density may play equally important roles in determining CA hemodynamics. Results in an anatomical model will also be presented. The proposed virtual coiling approach represents a novel and effective method for realistically simulating coiled CAs, and is an important step towards clinical preoperative planning of coil treatment.
Abstract WP92: Human Neural Stem Cells Enhance Synaptic Structural Remodeling in the Ischemic Brain.
Authors: Hiu Takeshi , Bliss Tonya M , Manley Nathan , Wang Eric H , Wang Gordon , Micheva Kristina D , Olson Andrew , Smith Stephen J , Steinberg Gary K
Published: July 2021

Introduction:
Stem cell transplantation has emerged as a promising new experimental treatment for stroke; understanding its mechanism of action will facilitate the translation of stem cell therapy to the clinic. Previous work from our lab and others suggests that transplanted stem cells function by enhancing endogenous brain repair processes including structural brain plasticity. The ultimate change in brain plasticity is manifested at the synaptic level and thus we hypothesize that stem cells will enhance synaptic structural remodeling in the post-ischemic brain. To test this we use array tomography, a new high-resolution proteomic imaging method, to determine a) the number and subtype of glutamate and GABA synapses after stroke, and b) how these parameters are affected by transplantation of human neural progenitor cells (hNPCs).

Method:
Vehicle or hNPCs derived from fetal cortex were transplanted into the ischemic cortex of Nude rats at 7 days after distal middle cerebral artery occlusion. Neurological recovery was assessed weekly using a battery of behavioral tests. Small tissue was removed from the peri-infarct cortex at 4 weeks post-transplantation. The tissue was processed and ribbons, or arrays, of serial ultrathin sections (70 nm) were obtained using an ultramicrotome. Ribbons were stained with antibodies for the synaptic markers Synapsin1, VGlut1, VGlut2, PSD-95, GAD, VGAT, GABAAR-α1, and images taken in cortical layer 2/3 and layer 5. Computational analysis of the resultant staining pattern was used to identify and quantify subtypes of glutamatergic and GABAergic synapses.

Results:
Transplantation of hNPCs significantly improved behavioral recovery after stroke compared to vehicle-treated rats (4 weeks; p<0.01, n=9). There was an increase in the density and proportion of glutamatergic synapses expressing VGluT2 in layer5 at 4 weeks post-transplantation (Density: 0.090 vs 0.057 synapses/μm3. Proportion: 27.0 vs 22.6 %, n=4). No detectable differences in the density of GABAergic synapses were observed.

Conclusions:
These results suggest that stem cells alter synaptic remodeling after stroke and this is coincident with stem cell-induced functional recovery.
Abstract 135: Antiplatelet Therapy Following Ischemic Stroke - Continue or Change Pre-existing Therapy?
Authors: Mazlan Kepli Wardati , Fulton Rachael L , Walters Matthew , Ali Myzoon , Bath Philip M , Dawson Jesse ,   on behalf of VISTA Collaborators
Published: July 2021

Introduction:
Antiplatelet therapy is routinely prescribed early after ischemic stroke. Many patients will already be taking antiplatelet therapy and it is unknown whether these patients should continue the same antiplatelet treatment or switch to a different regimen. We compared outcomes in patients who continued the same regimen after ischemic stroke to those who changed.

Methods:
Data from 10304 subjects were extracted from the Virtual International Stroke Trials Archive. 8550 subjects were excluded (12 incomplete data, 4823 no antiplatelet therapy recorded pre-stroke, 3715 no recorded antiplatelets post-stroke). Propensity score matching was employed to create a matched sample for comparison of those who continued the same regimen to those who changed. The nature of change in antiplatelet regimen was not explored. We compared the rate of recurrent stroke (primary endpoint), bleeding complications (defined as intracranial haemorrhage not including haemorrhagic transformation or any major bleed) and day-90 outcomes (using the modified Rankin and National Institutes of Health Stroke Scales). We used logistic regression analysis and adjusted for important clinical factors. Patients who suffered an outcome event prior to resuming antiplatelet therapy were not included in the analysis.

Results:
963 subjects changed antiplatelet regimen post stroke and 791 continued the same regimen. In the propensity matched sample (n=791 per group), a recurrent ischemic event occurred in 3.7% of subjects who changed regimen and 3.8% who continued unchanged (OR=1.078; 95% CI 0.62-1.88, p=0.790). The odds of better functional outcome were higher in the change group according to both day-90 mRS (OR=1.31; 95% CI 1.07-1.59, p=0.008) and NIHSS. The rate of intracranial bleeding and major bleeding within the first 90 days was similar in both groups (1.2% vs. 1.2% (p=0.939) and 2.4% vs. 3.2% (p=0.409) respectively).

Conclusion:
In patients who suffer ischemic stroke whilst taking antiplatelets, a change in antiplatelet regimen was not associated with reduced recurrent stroke rate or bleeding. Day 90 functional outcome was better in the change group but this may be due to a confounding variable.
Abstract 136: Is the Use of r-tPa in Mild Stroke Patients Cost-Effective?
Authors: Guzauskas Gregory F , Chen Er , Khatri Pooja , Sandercock Peter , Tayama Darren , Veenstra David L
Published: July 2021

Background:
The use of r-tPA in patients with moderate to severe stroke has been shown to be efficacious and cost-effective. However, nearly half of all ischemic strokes present with mild deficits (i.e. either persistently mild or rapidly improving stroke), and a third of untreated mild strokes result in significant disability. Small studies and post-hoc analyses of the recently completed IST-3 trial suggested r-tPA may reduce disability for mild stroke. If these preliminary clinical findings are verified, r-tPA in mild stroke patients may provide good economic value to healthcare systems.

Objective:
To model the potential cost-effectiveness of r-tPA in the treatment of mild stroke in the US.

Methods:
We developed a decision analytic model to simulate the outcomes of mild stroke patients treated vs. not treated with r-tPA. We modeled stroke severity health states based on modified Rankin scale (mRS) and Oxford handicap scale (OHS) scores using Markov techniques. Preliminary estimates of r-tPa effectiveness in patients suffering mild strokes were derived from a subset of IST-3 patients. Non-disabled patients were defined as having baseline NIHSS 0-15 who otherwise met all other standard three-hour r-tPA eligibility criteria. Healthcare costs, quality-adjusted life-years, and incremental cost-effectiveness were calculated, and scenario analyses were conducted to assess uncertainty.

Results:
Treatment with r-tPA was estimated to lead to a 0.36 (range, 0.34 to 0.76) increase in quality-adjusted life years per patient treated, and cost-savings ranging from $871 to $5500. In widely varying scenario analyses, as long as r-tPA treatment resulted in a 2% absolute increase in the proportion of non-disabled patients, r-tPA was highly cost effective. The main drivers in the results were r-tPA effectiveness, healthcare costs for disabled patients, and quality-of-life for non-disabled patients.

Conclusion:
Economic analyses based on preliminary clinical data suggest that r-tPA could be cost-saving or highly cost-effective in the treatment of mild patients. Controlled clinical trials will be valuable in definitively establishing the clinical and economic value of r-tPA in this patient population.
Abstract 17: Ischemic Stroke Profile, Risk Factors and Outcomes in India: The Indo-US Stroke Project
Authors: Sylaja PN , Pandian Jeyaraj , Kaul Subhash , Khurana Dheeraj , Srivastava Padma , Thankachan Tijy , Arora Deepthi , Titus Pritty , Singhal Aneesh
Published: July 2021

Background:
There is limited data about ischemic stroke in India. We characterized the clinical profile, risk factors and predictors of outcome after stroke in the Indian population, and investigated regional variations.

Methods:
The Indo-US Stroke Registry and Infrastructure Development Project, jointly funded by NINDS and the Indian Department of Biotechnology, currently includes 5 geographically diverse centers in North and South India and one in Boston, USA. Trained MD co-investigators and research coordinators prospectively collect data on consecutive adult patients with imaging-confirmed ischemic stroke <2 weeks after symptom onset. Data is entered into a central web-based electronic database.

Results:
From Nov-2012 to Jun-2013, 967 patients were enrolled. Mean age 59.7±13.9 yrs (range 20-92), 66% males. The patient population was 65% Hindu, 21% Sikh, 7% Christian, 6% Muslim, and 0.3% Jain; 58% had government health insurance. Only 3% arrived via EMS. Stroke risk factors included hypertension (66%), diabetes (39%), hyperlipidemia (20%), CAD (16%), atrial fibrillation (7.4%, rheumatic heart disease (5%). In addition to cigarette smoking (20%), exposure to beedi, hukkah, and smokeless tobacco (paan) was common (13%). The median admission NIHSS score was 9 (IQR, 5-15). Stroke subtypes using the automated ‘Causative Classification of Stroke’ program were large-artery atherosclerosis 31%, cardio-embolism 24%, small-vessel disease 15%, other defined causes 6%, and undetermined 24%. There were several regional differences, eg. hyperlipidemia, North 5% vs South 42% (p<0.001), good outcome (discharge mRS 0-2), North 45% vs South 57, p<0.001). Multivariate logistic regression analysis adjusting for age, gender and stroke severity showed that large artery atherosclerosis (OR 2.24, CI 2.18-2.37, p=0.02) and MCA territory strokes (OR 3.48, CI 2.02-3.67, p<0.0001) were predictors of poor outcome (mRS 3-6).

Conclusions:
The data provide insights about stroke in a large developing country. Resources are needed to address risk factors, regional differences, and develop the infrastructure for stroke care in India.
Abstract 171: Effect of Long-Term Treatment With Fimasartan on Transient Focal Ischemia in Rat Brain
Authors: Kim Chi K , Jung Seunguk , Kim Yerim , Kim Tae Jung , Kim Jun Yup , Ko Sang-Bae , Lee Seung-Hoon , Yoon Byung-Woo
Published: July 2021

Background and purpose:
Fimasartan is a novel angiotensin receptor blocker (ninth), and its safety and efficacy have been established as an antihypertensive drug. Anti-apoptotic or anti-inflammatory effects of angiotensin receptor blockers were reported. However, few studies have elaborated on the effects of long-term treatment with low-dose ARB on cerebral ischemia independent of blood pressure lowering.

Methods:
Noninvasive blood pressure monitoring was performed in Sprague-Dawley rats which 0.5 mg/kg of fimasartan or phosphate-buffered saline (PBS) were administered for 4 weeks. Fimasartan (0.5, 1 or 3 mg/kg) was administered intraorally for 4 weeks, and we induced ischemia-reperfusion injury in rats. Infarct volume and the number of TUNEL-positive apoptotic cells were measured at 7 days. Functional outcomes were evaluated by modified limb placing test. To identify the anti-inflammatory effect of fimasartan, the number of inflammatory cells (OX6-positive cells) was measured. To identify mediators, phospho-STAT3 and IkB proteins were measured via Western blot analyses at 48 hours.

Results:
Blood pressures were decreased after administration of 1 mg/kg or 3 mg/kg of fimasartan for 4 weeks, but were not decreased in 0.5 mg/kg group. All doses of fimasartan decrease infarct volumes, and low-dose fimasartan (0.5 mg/kg) maximally reduced infarct volume up to 70% of those of the control group (
p
< 0.05). Quantitative analysis showed that the number of TUNEL-positive cells was remarkably decreased in the low-dose fimasartan group (622 ± 57 cell/mm
3
vs. 235 ± 48 cells/mm
3
;
p
< 0.05). Low-dose fimasartan improved functional outcomes at 14 days (74% recovery in fimasartan group vs. 43% in control group;
p
< 0.05). The low-dose fimasartan group exhibited a lower number of OX6-positive cells (fimsartan group: 157 ± 17 cells/mm
3
; control: 86 ± 11 cell/mm
3
;
p
< 0.05). The IkB degradation as a marker of NF-kB activation, was delayed, and phospho-STAT3 was decreased in the low-dose fimasartan group (
p
< 0.05).

Conclusion:
We demonstrate that long-term treatment with fimasartan improves neurological outcome in transient focal ischemia in rats. This protective effect of fimasartan is independent blood pressure lowering.
Abstract 190: Allogeneic Marrow Stromal Cells Show Differences in Activation After Exposure to Blood From Healthy Subjects versus Stroke Patients
Authors: Parsha Kaushik , Guerrero Waldo , Yang Bing , Mir Osman , Hanley Patrick , Gee Adrian , Savitz Sean I
Published: July 2021

Background:
Systemic administration of marrow stromal cells (MSCs) leads to the release of a broad panel of cytokines and growth factors that may stimulate repair after stroke. However, the activation of MSCs may differ depending on the external environment they encounter after systemic injection. We explored the question whether the secretomes of MSCs, once exposed to systemic blood, differs depending on whether blood is from stroke patients versus healthy controls.

Methods:
Clinical grade bone marrow MSCs from a healthy donor at passage 2 were thawed and re-suspended in PBS. Peripheral blood from healthy subjects (n=4) and stroke patients (n=3) was collected. Blood from stroke patients was collected at 24 hrs after symptom onset. Whole blood or plasma was added to wells. PBS was then added with or without 200,000 MSCs. At various time points, aliquots were collected and probed for cytokines using a MAGPIX reader.

Results:
Placing MSCs in blood from healthy or stroke patients led to a differential release of cytokines (Fig 1). There were no changes in cytokines levels over time from wells that contained MSCs plus blood derived from healthy controls. However, there were significant increases in IL-8, IL-10 and VEGF levels in wells that contained MSCs plus blood from stroke patients (Fig 1). The increase in TNF-α in wells that contained blood alone from stroke patients was reduced by the addition of MSCs. In wells that contained MSCs plus plasma derived from stroke patients, there were very similar cytokine changes compared with wells that contained MSCs plus plasma derived from healthy controls (data not shown).

Conclusion:
The components of circulatory blood in stroke patients may be important to activate MSCs to release soluble factors that could modify brain recovery after stroke. Upon systemic administration, the exposure of MSCs to the microenvironment of blood might lead to different activation patterns depending on the health status of the individual.
Abstract 209: Association Between Pharmacologic Thromboprophylaxis and Hemorrhage Progression in Patients With Hemorrhagic Stroke
Authors: Levy A S , Salottolo Kristin , Coplin William M , Orlando Alessandro , Smith Richard , Santos Patricia , Bar-Or David
Published: July 2021

Background:
There is scant evidence on the safety of pharmacologic thromboprophylaxis (PTP) after hemorrhagic stroke. We sought to assess the association between PTP use and hemorrhage progression in patients who were diagnosed with primary hemorrhagic stroke.

Methods:
We reviewed patients with non-traumatic/spontaneous subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) from 1/2010 - 12/2012. We examined hemorrhage progression in two populations: patients with a stable initial f/u CT (no progression within one day of admission), and patients with an unstable initial f/u CT. Multivariate stepwise logistic regression was used to examine the association between hemorrhage progression and PTP.

Results:
In the 245 patients identified, 117 (48%) experienced hemorrhage progression. In the sub-group with unstable initial f/u CT (n=79, 32%) 24 patients (30%) had subsequent hemorrhage progression. Only one patient with an unstable initial f/u CT received PTP; thus, the association between PTP and subsequent hemorrhage progression was not analyzed further. Only SAH was independently associated with subsequent hemorrhage progression (OR: 4.3, p=0.03). In the sub-group with stable initial f/u CT (n=166, 68%), 38 patients (23%) had later hemorrhage progression; the rates of hemorrhage progression were similar for patients who received PTP and those who did not (26% vs. 22%, p=0.54). Variables that were independently associated with hemorrhage progression in the stable initial f/u CT group include non-ambulatory status (OR: 7.8, p=0.002), minor stroke (NIHSS<8, OR: 4.1, p=0.02), male gender (OR: 4.4, p= 0.01), and hospital LOS (OR: 1.1/day, p< 0.001); receiving PTP was not a predictor (OR: 0.6, p=0.42).

Conclusions:
This study demonstrated that in patients whose initial f/u CT was stable, the use of PTP was not associated with an increased risk of hemorrhage progression. There was insufficient evidence to determine the relationship between PTP and subsequent progression in the unstable f/u CT population. These data suggest that PTP may be safe in patients with hemorrhagic stroke whose initial f/u CT is stable.
Abstract 216: Risk of Thrombosis Remains Elevated for 12 Weeks After Labor and Delivery
Authors: Kamel Hooman , Navi Babak B , Sriram Nandita , Hovsepian Dominic A , Elkind Mitchell S
Published: July 2021

Background:
The risk of arterial and venous thrombosis remains elevated during the conventionally defined 6-week postpartum period, but it is unknown whether heightened risk persists beyond this point. Given the magnitude of postpartum thrombotic risk, we hypothesized that it remains elevated beyond 6 weeks after labor and delivery.

Methods:
Using administrative claims data from all nonfederal acute care EDs and hospitals in California, we compared the risk of thrombotic events during sequential 6-week periods after delivery. We used validated ICD-9-CM codes to identify women hospitalized for ischemic stroke, acute MI, PE, or DVT; in a sensitivity analysis we included a broader list of thrombosis codes, including cerebral sinus thrombosis. We compared each patient’s likelihood of labor and delivery in the 0-to-6 week period before a thrombotic event (case period) versus a 6-week period exactly 1 year prior (control period). We repeated this case-crossover analysis for the 6-to-12 week, 12-to-18 week, and 18-to-24 week periods before the thrombotic event. Odds ratios for each time period were calculated with conditional logistic regression because each patient was matched to her own control period.

Results:
Of 648,148 women with a first documented thrombotic event between 2007 and 2011, 1,620 had delivered during the prior 24 weeks. Their mean age was 30 (±7) years; 16% were black and 35% Hispanic. The risk of thrombosis was markedly higher in the 0-to-6 week period after delivery (OR, 6.6; 95% CI, 5.1-8.4) versus 1 year prior. Notably, thrombotic risk remained elevated during the 6-to-12 week period after delivery (OR, 2.3; 95% CI, 1.8-3.1). The risk then essentially normalized in the 12-to-18 week period (OR, 1.2; 95% CI, 0.9-1.6) and fully resolved in the 18-to-24 week period (OR, 0.9; 95% CI, 0.7-1.2). This pattern was similar in our sensitivity analysis and when we assessed the specific endpoints of stroke, acute MI, and PE or DVT.

Conclusions:
The risk of thrombosis remains elevated beyond the traditional 6-week postpartum period, and persists for at least 12 weeks after delivery. This should be considered when evaluating postpartum women with symptoms of possible thrombosis, or making recommendations about postpartum thrombosis prophylaxis or treatment.
Abstract 22: New Silent Brain Infarcts after Coronary Artery Bypass Graft Surgery: Lesion Patterns, Mechanism, and Predictors
Authors: Nah Hyun-Wook , Lee Jae-Won , Chung Cheol-Hyun , Choo Suk-Jung , Kwon Sun U. , Kim Jong S. , Warach Steven , Kim Eung-Gyu , Kang Dong-Wha
Published: July 2021

Objectives:
To investigate the lesion patterns and predictors of silent brain infarction after coronary artery bypass graft (CABG) surgery and propose a mechanism.

Background:
New brain infarcts after CABG are markedly more frequent than clinically evident stroke and are thought to be associated with postoperative cognitive decline. Thus, identification of the mechanism and risk factors of postoperative silent brain infarction may be clinically relevant.

Methods:
This was a prospective pre- and postoperative brain MRI study in consecutive patients who underwent isolated CABG. Preoperative MRI included diffusion-weighted imaging (DWI) and magnetic resonance angiography. DWI was repeated on postoperative day 3. Clinical variables, intraoperative findings, and laboratory findings were compared between patients with and without new brain infarcts on DWI.

Results:
Of a total of 127 included patients, 35 (27.6%) showed new brain infarcts on DWI. Most lesions were clinically silent, were located in the cortical territory (80%), were small (<1.5 cm) in diameter (89%), and were not related to the underlying cerebral arterial abnormality (80%) (Figure). Old age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.03-1.15), use of cardiopulmonary bypass (OR, 3.12; 95% CI, 1.13-8.57), a moderate to severe aortic plaque (OR, 21.17; 95% CI, 2.01-222.58), and high levels of high-sensitivity C-reactive protein (OR, 1.35; 95% CI, 1.08-1.70) were independent predictors of new brain infarction.

Conclusions:
New brain infarcts on DWI after CABG are frequent and mostly silent. Aortogenic embolisms and a systemic inflammatory response may contribute to the pathogenesis of new brain infarcts.
Abstract 25: Paroxysmal Atrial Fibrillation is Common in Patients With Defined Etiology for Stroke: Prolonged Monitoring of Cardiac Rhythm for Detection of Atrial Fibrillation After a Cerebral Ischemic Event (PEAACE) Study
Authors: Ghrooda Esseddeeg M , Dobrowolski Peter , Basir Ghazala , Yaseen Ibrahim , khan Nazim , Ahmad Aftab , Hasan Mustafa , GulamHusain Sajad , Mohammad Askar , SHUAIB Ashfaq
Published: July 2021

Introduction:
Atrial fibrillation (AF) related cardioembolic stroke accounts for over 20% of ischemic stroke. Recent reports using prolonged cardiac rhythm monitoring (PCRM) in cryptogenic stroke reveal paroxysmal AF (PAF) in an additional 20% of patients. We report our findings with PCRM in patients with and without cryptogenic stroke patients in whom an initial 24-h Holter was negative.

Methods:
Patients admitted to the stroke service with no previous history of AF and no AF on Holter monitoring were enrolled for 3 weeks of PCRM. We used a PAF predictive score to determine the risk of the arrhythmia. All studies were interpreted by the stroke team prior to final review by the cardiologist.

Results:
Between Sept 2012 and June 2013, 96 patients were evaluated. Over all PAF was diagnoses in 37.5 % of patients. PAF was diagnosed in 32% of patients with cryptogenic stroke and 36 % of patients where an additional etiology may account for the stroke diagnosis. The AF prediction score was not useful in the recognition of patients that were more likely to be at risk for AF. 96 of 98 recordings were correctly identified by the stroke team prior to final diagnosis by the cardiologist.

Interpretation:
PAF is more common in stroke patients than was previously suspected. It occurs with similar frequency in patients with and without cryptogenic stroke. Our data strongly supports the need for prolonged cardiac rhythm monitoring in all stroke patients to diagnose this important preventable cause of ischemic stroke.
Abstract 28: “Defining The Undefined”- Rapidly Improving Stroke Symptoms: A Systematic Review of the Literature.
Authors: Piran Pirouz , Balucani Clotilde , Ramkishun Charles , Tariq Sara , Lederman Yitzchok S , Tark Brian E , Levine Steven R
Published: July 2021

Background:
“Rapidly Improving Stroke Symptoms” (RISS) is a major exclusion criterion for tPA treatment in acute ischemic stroke (AIS).

Objectives:
To explore various definitions used for RISS and reported clinical outcomes of RISS patients, treated and untreated with tPA.

Methods:
A systematic review of the literature(through Aug 5, 2013)for studies reporting definition or outcome data for RISS or both, was performed by 3 independent reviewers using prespecified medical subjects heading (MeSH) terms, Boolean logic and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

Results:
From 97 potentially eligible articles identified via abstract review, 35 were excluded for inadequate data. Of the 62 articles remaining: 38 did not provide definitions for RISS; 9 reported data of RISS with minor stroke together while 15 considered them separately and reported 5 different definitions of RISS: 1) physician judgment (n=9); 2) ≥4 point reduction in NIHSS score from initial to tPA decision time (n=3); 3) general impression of significant improvement before tPA(n=1); 4)major symptoms rapidly improving by the time of decision (n=1); 5) documented significant improvement in at least 4of the following items - motor paresis of arm, - leg or - facial muscles, - aphasia - dysarthria and - sensory deficit - (n=1). RISS outcome data was reported separately from minor stroke in 5/62 (8%) studies: 1) favorable outcome (mRS=0-1, NIHSS= 0-1) at 3 months were reported in 15/19 (78%) of RISS patients given tPA; 2) 25/57 (44%) of RISS patients were dependent/died at discharge; 3)13/27 (48%) of RISS had favorable outcome; 4) 4/10 (40%) RISS patients were discharged home; RISS patients were more likely than non-RISS to have large-artery occlusion (5/10 versus 3/31; P=0.01); 5)In 39 RISS patients there was an association between NIHSS ≥10 and unfavorable outcome at 3 months (p=0.026).

Conclusions:
There is no generally accepted definition for RISS and in most cases it is left to the physician’s judgment, which varies. A high proportion of AIS patients excluded from tPA solely because of RISS have poor outcome. Future research needs to validate RISS definitions and determine how different definitions predict clinical outcome.
Abstract 29: The Surgical Trial in Lobar Intracerebral Haemorrhage - Analysis of Crossover Patients
Authors: Gregson Barbara A , Rowan Elise , Mendelow A D ,   STICH II Investigators
Published: July 2021

Background:
STICH II was an international multicentre pragmatic randomised parallel group trial to establish whether a policy of early surgery (ES) improved outcome compared to a policy of initial conservative treatment (ICT) for patients with superficial lobar intracerebral haemorrhage (ICH). The results of the “intention to treat analysis” have been published and showed a non-significant trend in favour of early surgery. However, as observed in other surgical trials, there was a substantial crossover of patients from the ICT group with 21% having surgery within 14 days of randomisation. This paper investigates these patients and their effect on outcome.

Methods:
Patients from the ICT group who underwent surgery within 14 days were identified and compared with patients who continued to receive conservative treatment and with patients randomised to ES. The protocol defined “early surgery” as within 12 hours of randomisation so analyses were also conducted using this definition. Per protocol and treatment received analyses were conducted.

Results:
For this analysis there are 285 ICT patients with outcome assessed, 233 had no surgery and 62 patients had surgery within 2 weeks: 23 within 12 hours. Of 297 patients randomised to ES, 278 had surgery within 12 hours. Surgical ICT patients had lower GCS (13 v 14) and larger volumes (54ml v 32ml) of haematoma at randomisation (p<0.0001) than non-surgical ICT. They also showed lower GCS and larger volumes (54ml v 40ml) than per protocol ES patients. Surgical ICT patients were much more likely to have an unfavourable outcome than non-surgical (84% v 63%, p < 0.002). If the surgery was after 12 hours the unfavourable outcome was higher (89%). There were no differences in outcome between per protocol ES and non-surgical ICT but there were major differences in baseline measures between these patients.

Death rates were highest in ICT patients having surgery within 12 hours (48%) compared with later surgery (31%), non-surgical ICT patients (20%) and ES patients (17%).

Conclusions:
Patients randomised to conservative treatment who deteriorate and have surgery differ considerably from those that do not deteriorate and from those who are randomised to early surgery. Further work is needed to develop ways of analysing these data.
Abstract 39: Infection, Vaccination, and Childhood Stroke: Preliminary Results of the Vascular Effects of Infection in Pediatric Stroke (VIPS) Study
Authors: Hills Nancy K , DeVeber Gabrielle A , Glaser Carol A , Wintermark Max , Elkind Mitchell S , Fullerton Heather J ,   on behalf of the VIPS Investigators
Published: July 2021

Background:
Acute minor infection was associated with childhood arterial ischemic stroke (AIS) in a retrospective study. In a prospective study, we tested the hypothesis that acute infection increases stroke risk, while vaccination against infection is protective.

Methods:
VIPS is an international multi-center prospective case-control study with a target enrollment of 350 cases of AIS (28 days-18 years old); parental interviews were conducted within 3 weeks of stroke occurrence in cases. Unmatched controls were identified and interviewed within 3 weeks of routine clinic visits for annual check-ups, migraine, or developmental delay, or urgent visits for trauma. Data were collected on recent infections and routine childhood vaccines. We explored attitudes toward vaccination by asking if the child had received all, most, some, few, or none of the routine vaccines expected for his/her age.

Results:
Data were available for 310 cases and 289 controls. Median (IQR) age was 7.5 (2.8, 14.2) and 8.2 (3.3, 12.8) years respectively (p=0.96). Infection ≤1week prior to stroke/interview date conferred a 6.5-fold risk of AIS (p<0.0001); the most common type of infection reported in this time period was upper respiratory (75% of controls and 50% of cases). In general, cases were under-vaccinated compared to controls (Table). Children reported to have had some/few/no routine vaccinations were at higher risk of AIS than those receiving all or most (OR 6.72, 95% CI 2.30, 19.6, p<0.0001). In logistic regression adjusted for age, ever having received an MMR, polio, or pneumococcus vaccine were each significantly protective against stroke.

Conclusions:
Recent infection confers an increased risk of childhood AIS, while routine vaccinations appear protective. This finding has positive implications for both primary and secondary stroke prevention.
Abstract 4: Excellent Collaterals in STAR: Minimal Infarct Core Trumps the Degree of Hypoperfusion
Authors: Liebeskind David S , Scalzo Fabien , Johnson Mark S , Dávalos Antoni , Bonafé Alain , Castaño Carlos , Chapot René , Arnold Marcel , Sztajzel Roman , Liebig Thomas , Goyal Mayank , Besselmann Michael , Moreno Antonio , Schroth Gerhard , Gralla Jan , Pereira Vitor M , Nogueira Raul G ,   for the STAR Investigators
Published: July 2021

Background:
Collateral grade on DSA before acute endovascular therapy of stroke predicts revascularization. Excellent collaterals were a potent predictor of good clinical outcomes at 90 days after treatment in Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR). We studied whether excellent collaterals could be detected with either CT or MR perfusion imaging acquired immediately before treatment.

Methods:
Independent angio and CT/MRI core labs analyzed baseline DSA ASITN/SIR collateral grade and CT/MR perfusion imaging volumes (equivalent definitions of infarct core and Tmax > 4, 6, 8, 10, 12, 14 s). Hypoperfusion was defined as Tmax > 6s, with Tmax hypoperfusion intensity ratios of 10/6 and 14/6, and target and malignant profiles based on DEFUSE-2. Excellent collateral grade (3-4) was analyzed by pretreatment CT/MRI patterns.

Results:
64 of 202 cases in STAR (mean age 67.9 ± 13.1 years; 53% women; median baseline NIHSS 15 (8-25)) had CT/MR perfusion volumes and ASITN/SIR collateral grade analyzed. Distribution of collateral grade (0, n=2; 1, n=31; 2, n=14; 3, n=15; 4, n=2) was similar to the entire STAR population. Excellent collaterals were unrelated to age and gender, with a trend towards lower NIHSS (OR 0.9, p=0.12). Excellent collaterals in 17/64 (27%) demonstrated very small core volumes (0 cc, n=8; 1-25 cc, n=8; > 25 cc, n=1) compared to other cases. Similarly, clinical-core mismatch (defined as baseline NIHSS ≥8-16 and core ≤ 25 cc; baseline NIHSS ≥17 and ≤ 50 cc) was noted in 16/17 (94%). The extent of hypoperfusion (Tmax > 6s) and degrees of hypoperfusion (Tmax 4-14, 10/6, and 14/6) were not related to the presence of excellent collaterals. Target mismatch (n=53/64, 83%) showed an OR 4.32 (p=0.18) for excellent collaterals and no malignant profiles were associated with grade 3-4.

Conclusions:
CT/MR perfusion patterns prior to endovascular therapy are associated with excellent collaterals, evident as very small infarct core, target mismatch, and clinical-core mismatch. The degree of Tmax hypoperfusion severity alone cannot be used to identify presence of excellent collaterals.
Abstract 65: Effect of Prestroke Statin Use on Stroke Severity and Early Functional Recovery
Authors: Choi Jay Chol , Hong Keun-Sik , Lee Ji Sung , Park Tai Hwan , Park Jong-Moo , Kang Kyusik , Cho Yong-Jin , Lee Soo-Joo , Ko Youngchai , Lee Jun , Kim Joon-Tae , Yu Kyung-Ho , Oh Mi-Sun , Lee Byung-Chul , Cha Jae-Kwan , Kim Dae-Hyun , Lee Juneyoung , Kim Dong-Eog , Jang Myung Suk , Kim Beom Joon , Bae Hee-Joon
Published: July 2021

Background:
Experimental studies suggest that prestroke statin treatment has dual effect of neuroprotection during ischemia and neurorestoration after ischemic injury. However, human clinical stroke studies of small to modest sample sizes have shown inconsistent results regarding these effects.

Methods:
We analyzed the Clinical Research Center for Stroke-5 data set for patients hospitalized with acute ischemic stroke in 12 academic hospitals between April 1, 2008 and January 31, 2012. Primary endpoint was the initial stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS) score. Secondary endpoints were mRS 0-2 proportion and overall distribution of mRS outcomes at discharge. Propensity score (PS) analysis were used to adjust baseline characteristics between statin users and non-users in addition to multivariable analyses.

Results:
Among 8,340 patients included in this study (age, 67±13 years; men, 59.6%; initial median NIHSS score [interquartile range, IQR], 3 [2-7]), 964 patients (11.6%) were taking statins before the index stroke. Prestroke statin users had significantly lesser initial NIHSS score than that of non-users (unadjusted mean [95% CI], 4.6 [4.3-4.9] versus 5.4[5.3-5.6], p <0.0001; median [IQR]), 3 (IQR, 1-6) versus 3 (IQR, 2-7) , p <0.0001).The difference remained significant after adjustment for covariates (adjusted mean, 6.0 [5.5-6.5] versus 6.6 [6.1-7.0]; p=0.0062) as well as PS-matched cohort (adjusted mean, 4.8[4.3-5.2] versus 5.4[5.1-5.7], p=0.0298). After adjusting for covariates including initial NIHSS score, statin users had more frequent mRS 0-2 outcome (adjusted OR [95% CI], 1.50 [1.21-1.86]; p=0.0002) and greater favorable shift on the mRS score at discharge than those of non-users (adjusted OR [95% CI], 1.26 [1.08-1.48]; p=0.003). In PS-matched cohort, similar associations were also found for dichotomized outcomes (adjusted OR [95% CI], 1.55 [1.22-1.97]; p=0.0003) and for ordinal outcomes (adjusted OR [95% CI], 1.28 [1.07-1.52]; p=0.0058).

Conclusions:
Prestroke statin use was independently associated with lesser stroke severity at presentation and better early functional outcome, suggesting dual effect of neuroprotection and neurorestoration in human clinical strokes.
Abstract 7: Differential Effect of Baseline Cta Collateral Status on Clinical Outcomes in Patients Enrolled in the Ims-3 Trial
Authors: Menon Bijoy K , Qazi Emmad , Nambiar Vivek , Foster Lydia D , Yeatts Sharon , Liebeskind David , Jovin Tudor , Hill Michael D , Goyal Mayank , Tomsick Tom , Broderick Joseph , Demchuk Andrew M
Published: July 2021

Introduction:
In the IMS 3 trial, we test the hypothesis that a differential effect of endovascular therapy on clinical outcome will be most apparent in patients with severely ischemic but salvageable brain tissue (moderate collaterals on baseline CTA).

Methods:
Data is from patients in the IMS 3 study. Of 656 patients in the study, 306 patients had baseline CTA and 204 patients had M1 MCA +/_ intracranial ICA occlusion where baseline collaterals could be measured. Collateral status was assessed by consensus using 3 different scores and categorized as good, intermediate and poor. Details of the IMS 3 study protocol are described in the primary paper.

Results:
Of 204 patients, 138 received endovascular therapy (85.7% recanalized, 44.2% achieved 90-day mRS 0-2) and 66 received IV tPA only (57.1% recanalized, 36.4% achieved 90-day mRS 0-2). Proportion of patients with 90-day mRS 0-2 in good, intermediate and poor collateral categories between endovascular therapy and IV tPA across the 3 scores were: score 1(good: 56.5% vs. 41.7%, intermediate: 45.2% vs. 22.2%, poor: 18.4% vs. 23.5%); score 2 (good: 57.4% vs. 42.3%, intermediate: 40% vs. 23.1%, poor: 5.3% vs. 14.3%); score 3 (good: 51.6% vs. 42.3%, intermediate: 43.3% vs. 23.5%, poor: 20.6% vs. 18.8%). Using the van-Elteren test, a significant shift in 90-day mRS distribution in favor of endovascular therapy was noted only for subjects with intermediate collaterals. (p=0.01 for scores 1 and 2, Figure 1) Clinical outcome was poor with no differential effect of therapy in patients with poor collaterals.

Conclusion:
Patients with baseline intermediate collaterals have the highest likelihood of showing better clinical response to endovascular therapy. Future clinical trials testing IV tPA vs. endovascular therapy may have a higher likelihood of showing differential treatment effect if patients with baseline poor collaterals are excluded.
Abstract 70: Risk of Hemorrhage in Veterans Who Switch to Dabigatran for Stroke Prevention in Atrial Fibrillation
Authors: Vaughan Sarrazin Mary , Jones Michael , Cram Peter , Mazur Alexander
Published: July 2021

BACKGROUND:
The REL-Y trial found similar rates of hemorrhage for dabigatran and warfarin in patients with atrial fibrillation (AF). These findings have not been evaluated in real world clinical settings. OBJECTIVE: We used national administrative Veterans Affairs (VA) data from 2011-2012 to evaluate the risks of any bleeding, intracranial bleeding, and gastrointestinal bleeding for patients who switched to dabigatran after at least 6 months on warfarin, compared to patients remained on warfarin.

DATA:
We identified 93,950 patients with AF who had been on warfarin for at least 180 days during the data period, including 1419 (1.5%) who subsequently received dabigatran. Baseline and time-dependent patient characteristics identified included comorbid conditions, CHADS2 stroke risk score, HAS-BLED bleeding risk score, and INR time in therapeutic range. For each type of bleed, the date of the first bleeding event after June 2011 was identified. The use of dabigatran or warfarin during the follow up period was identified using VA National Pharmacy Extracts.

ANALYSIS:
Marginal structural models (MSM) were used to determine the hazard of bleeding with dabigatran relative to warfarin. MSM use weights to reduce bias in observational data caused by nonrandom censoring or treatment assignment. The weighted logistic regression models were fit using generalized estimating equations, and reflected baseline and time dependent covariates (e.g., HAS-BLED, CHADS2), weekly indicators of anticoagulant type (warfarin or dabigatran), and censoring events (e.g., ceasing anticoagulation therapy, death).

RESULTS:
Compared to patients who never used dabigatran, patients who used dabigatran at least once were younger, more likely to be white, had lower INR time in therapeutic range on warfarin, lower CHADS2 scores, and similar HAS-BLED scores. A total of 21,083 patients experienced bleeding events, including 129 events after dabigatran use. Risk adjusted rates of any bleeding and intracranial bleeding were similar for warfarin and dabigatran. However, the likelihood of gastrointestinal bleeding was 70% higher with dabigatran use.

CONCLUSIONS:
Dabigatran may increase the likelihood of gastrointestinal bleeds, but is not associated with other bleeding.
Abstract 74: Early Arterial Recanalization After Intra-venous Tissue-Plasminogen-Activator Treatment in the Interventional Management of Stroke-3 Study
Authors: Von Kummer Ruediger , Demchuk Andrew M , Foster Lydia D , Yan Bernard , Schonewille Wouter J , Goyal Mayank , Broderick Joseph P , Tomsick Thomas A
Published: July 2021

Background:
Data on arterial recanalization after IV t-PA treatment are rare. IMS-3 allows the study of variables affecting arterial recanalization after IV t-PA in acute ischemic stroke patients with CTA-proved major artery occlusions.

Methods:
Of 656 acute ischemic stroke patients in IMS-3, 306 were examined with baseline CTA and randomized either to IV t-PA (N=95) or to IV t-PA followed by digital subtraction angiography (DSA) and endovascular therapy (EVT) (N=211). Comparison of baseline CTA to DSA within 5 hours of stroke onset assessed early arterial recanalization after IV t-PA. A central core lab categorized DSA vessel occlusion as “no, partial, or complete”. We studied the association between arterial occlusion sites on baseline CTA with early recanalization for the endovascular group and analyzed its impact on clinical outcome at 90 days.

Results:
In the EVT group, 22 patients (10.4%) had no CTA intracranial occlusions, but 1 extracranial occlusion; 42 patients (19.9%) had occlusions of intracranial internal carotid artery (ic-ICA); 10 patients (4.7%) had tandem occlusions of the cervical ICA and middle cerebral artery (MCA); 95 patients (45.0%) had MCA-trunk (M1) occlusions, 33 patients (15.6%) had M2 occlusions, 3 patients (1.4%) had M3/4 occlusions, and 6 patients (2.8%) occlusions within posterior circulation. Partial or complete recanalization occurred in 28.6% of patients before DSA and was marginally associated with occlusion site (p=0.0525) (8 patients (19.0%) with ic-ICA occlusion, 0 patients with tandem ICA/MCA occlusions, 34 patients (35.8%) with M1 occlusions, 11 patients (33.3%) with M2 occlusions, 0 patients with M3/4 occlusions, and 1 patient (16.7%) with occlusion within posterior circulation). Three CTA negative patients had intracranial occlusions on DSA. Thirty-two patients (59.3%) with early recanalization achieved mRS of 0-2 at 90 days compared to 51 patients (38.4%) without early recanalization (p=0.0099). There was no relationship between early recanalization and time to IV t-PA or mean t-PA dose.

Conclusion:
Before EVT, IV rt-PA may facilitate arterial recanalization and better clinical outcome in about one third of patients.
Abstract 77: Comparative Efficacy of Different Acute Reperfusion Therapies for Acute Ischemic Stroke: A Comprehensive Meta-analysis of Clinical Trials
Authors: Tsivgoulis Georgios , Alleman John , Barreto Andrew D , Molina Carlos A , Alexandrov Andrei V
Published: July 2021

Background&Purpose:
There are limited data directly comparing acute reperfusion therapies (RPT) for the treatment of acute ischemic stroke (AIS) in the setting of randomized controlled trials. We conducted a comprehensive meta-analysis of available clinical studies of acute RPT to indirectly compare them using a benefit-to-risk analysis.

Subjects&Methods:
We abstracted data from 16 RPT studies evaluating intravenous thrombolysis (IVT) using alteplase or tenecteplase (TAAIS, NINDS), sonothrombolysis (CLOTBUST) intra-arterial thrombolysis (PROACT I&II, IMS III, SYNTHESIS pilot&expansion study) and acute thrombectomy/thromboaspiration using different retrievers (MERCI, Multi-MERCI, PENUMBRA Pivotal Stroke Trial & Post Market Experience, SWIFT, TREVO, TREVO 2, MR Rescue). The benefit-to-risk ratio (BRR) was estimated separately for each study using the following formula: BRR= (% of 3-month mRS of 0-1/ % of 3-month mRS of 6) x (median baseline NIHSS of study of interest/median baseline NIHSS of all evaluated studies).

Results:
The BRRs of all analyzed studies (median pre-treatment NIHSS 17 points) plotted against time to intervention are shown in Figure. The BRRs ranged from 0.31 in the MR Rescue endovascular arm to 5.80 in the high-dose of tenecteplase in TAAIS. The most effective RPTs were: IVT with tenecteplase in TAAIS (BRR 5.80), sonothrombolysis (BRR 2.75), followed by IVT with alteplase in SYNTHESIS expansion trial (BRR 2.68). The endovascular arm of TREVO had the highest BRR (1.70) among the acute thrombectomy studies evaluating different devices. BRR strongly correlated with time to treatment from symptom onset (R2:0.640; p<0.0001)

Conclusions:
IVT with a novel agent followed by sonothrombolysis appear to be associated with the highest BRR. Almost two thirds of the variation of BRR can be explained by differences in onset-to-treatment time between studies indicating a strong time-dependency of BRR in acute RPT.