bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP107: Neuroimaging Characteristics of Intracranial Hemorrhages and Microhemorrhages in Infective Endocarditis
Authors: Cho Sung-Min , Marquardt Robert , Zhang Lucy , Thatikunta Prateek , Uchino Ken , Wisco Dolora
Published: June 2021

Introduction:
Intracranial hemorrhage (ICH) is common in infective endocarditis (IE). We explored the imaging characteristics, predictors, and clinical implications of ICHs including intraparenchymal hemorrhage (IPH), and subarachnoid hemorrhage (SAH) and, subdural hematoma (SDH).

Methods:
We reviewed records of 116 consecutive acute IE patients by Duke’s criteria with neurological consultation or admission to stroke neurology service in a single tertiary referral center from January 2015 to July 2016. ICHs were defined as IPH, SAH, or SDH seen on CT. Microhemorrhages were identified on susceptibility weighted imaging (SWI) on MRI. Patient’s radiographic characteristics and complications were collected.

Results:
Of 116 patients, 25 persons (21.6%, median age 58) had ICHs, 14 with IPHs, 7 with SAHs, 3 with both IPH and SAH, and 1 SDH. Of 17 (14.7%) IPHs (median NIH Stroke Scale 6 and median volume 38.6cc), 10 (8.6%) IPHs were symptomatic and 7 IPHs were silent. Eleven persons (65%) with IPH also had ischemic strokes. Mycotic aneurysms were identified only in 1 (4.8%) in 21 persons with ICH who underwent cerebral angiogram. MRIs identified 66 persons with microhemorrhages (56.9%, median age 58.5) among 85 who underwent MRI. Eighteen (72%) of 25 persons with ICHs had microhemorrhages in SWI. In multivariate logistic regression analysis, ICH was associated with the presence of >5 microhemorrhages (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.04-1.50) and staphylococcus aureus (OR: 1.25, 95% CI: 1.03-1.51). Ten persons (40%) with ICH died (7 with IPH and 4 with SAH) in the same hospitalization. Thirteen persons (52%) with ICH (median 21.4cc in 9 IPHs) underwent valve replacement at median of 13.5 days and 2 persons had new non-fatal strokes (1 IPH and 1 ischemic stroke).

Conclusions:
Intracranial macro- or micro-hemorrhages are seen in 73 (63%) persons with IE. The mortality of intracranial hemorrhage is high but the perioperative stroke risk appears low.
Abstract WMP108: A Root-Cause Analysis of Symptomatic Rebleeding With Clot Lysis: Evaluation of Accelerated Resolution of Intraventricular Hemorrhage Phase III Clinical Trial (CLEAR III)
Authors: Fam Maged D , Stadnick Agnieska , Zeineddine Hussein , Girard Romuald , Mayo Steven , Dlugash Rachel , McBee Nichole , Lane Karen , Mould Andrew , Kase Carlos , Ziai Wendy , Hanley Daniel , Awad Issam
Published: June 2021

Background:
Thrombolytic therapy after intraventricular hemorrhage (IVH) is being used with increasing frequency in recent years, and was recently evaluated in a randomized, placebo controlled blinded prospective clinical trial (CLEAR III). Hemorrhagic complications have remained a concern with thrombolysis in hemorrhagic stroke. We herein present a root case analysis of all cases with adjudicated symptomatic rebleeding identified in the CLEAR III Trial.

Methods:
We reviewed safety reports on symptomatic rebleeding events encountered within one year from randomization among subjects enrolled in CLEA III trial, with prospectively articulated definitions and reporting standards. Medical and imaging data were retrieved through the trial database. We analyzed clinical presentation, baseline and follow-up imaging, laboratory abnormalities, medical and surgical management aspects that may have contributed to rebleeding. Subjects were individually analyzed and classified according to onset of (dosing period, early post-dosing and delayed) rebleeding, pattern of bleeding and treatment rendered (alteplase vs. saline), and potential factors contributing the rebleeding.

Results:
Twenty-one subjects developed a secondary symptomatic hemorrhage constituting 4% of subjects in the trial. Symptomatic rebleeding events took place during the dosing protocol (n=9, 6 in the alteplase group), early after the protocol (n=6, 2 in the alteplase group) and late (n=6, none in the alteplase group). Catheter-related hemorrhages were the most common (n=7, 33%) followed by intraventricular (n=6, 30%) and intracerebral hemorrhage (n=5, 25%). Rebleeding during the dosing period resulted from a combination of treatment- and patient-related factors and could be partially attributable to alteplase in 6 of 9 cases. Rebleeding after the dosing protocol was primarily dependent on patients’ risk factors.

Conclusion:
Overall risk of symptomatic hemorrhagic complications are low after intraventricular thrombolysis for IVH as long as safety protocols are followed as deployed in the clinical trial. Secondary prevention strategies are needed following the acute care phase to minimize rebleeds.
Abstract WMP114: The Role of Hypoxemia and Hypercapnia as Risk Factors for Childhood Stroke
Authors: Toutounji Sandra , Narang Indra , Surmava Ann-Marie , Dlamini Nomazulu
Published: June 2021

Background:
Risk factors for childhood stroke differ significantly from those in adults. Obstructive Sleep Apnea (OSA) is an independent risk factor for adult stroke. Children with Sickle Cell Disease (SCD) have a higher prevalence of OSA than the general pediatric population, and nocturnal hypoxemia in these patients is independently predictive of future CNS events. Hypoxemia and hypercapnia secondary to OSA result in a pro-inflammatory and prothrombotic cascade associated with metabolic dysregulation and endothelial dysfunction.

Hypothesis:
We hypothesized that OSA, hypoxemia and/or hypercapnia are associated with an increased stroke risk in a pediatric population.

Methods:
Clinical and radiologic data of consented children seen in the stroke program from 1992-2014 with clinically indicated sleep study/polysomnography (PSG) were retrospectively reviewed and analyzed.

Results:
Thirty-one children (31/947; 14 male, mean age at PSG 8.4 years) were identified. Twenty-three children had arterial ischemic stroke (AIS) (mean age 7.6 years, SEM 0.99 years) and eight were non-stroke arteriopathy patients (mean age 10.5 years, SEM 1.16 years). Children diagnosed with AIS had significantly higher prevalence of OSA than children with no stroke (69% vs. 25%, p=0.0429) regardless of the timing of sleep study (11/15, 73.3% OSA post-stroke diagnosis and 5/8, 62.5% OSA pre-stroke diagnosis). AIS patients had significantly lower minimum SaO2 values overnight (83.19% vs. 94.56%, p=0.0072), and higher overnight mean end tidal (et) and transcutaneous (tc) CO2 levels (et CO2 42.78 vs. 41.75 mmHg, p=0.4940; tc CO2 42.08 vs. 39.67 mmHg, p=0.3544). Primary risk factors of AIS in children with clinically indicated PSG included 3 moyamoya (33% with OSA), 8 cardiac (63% with OSA), 5 SCD (83% with OSA), and 7 other (86% with OSA). Cardiac patients had the lowest nocturnal SaO2 and highest CO2 levels when compared to moyamoya, SCD and others.

Conclusions:
In our study, children with AIS were more likely to have OSA and nocturnal hypoxemia, highlighting these as potential risk factors for stroke in childhood. Future prospective studies are required to explore the relationship between stroke, hypoxemia and hypercapnia.
Abstract WMP119: Evaluating Discharge Patterns in the Stroke Population
Authors: Hamm Theresa
Published: June 2021

Hypothesis:
Determining discharge patterns in the stroke population will assist in directing appropriate resources and patient outcomes.

Methods:
A retrospective review of 917 records was completed at a Joint Commission Certified Primary Stroke Center. Only patients with a confirmed diagnosis of stroke were included. Discharge destination was evaluated as well as NIHSS scores (which were then averaged) and stroke subtype. An assessment of rationale for patients not receiving Activase was also completed.

Results:
The following table illustrates the results of this review.

This subset was further evaluated for non-treatment rationale; 80% arrived outside a treatment window; 13% were mild or rapidly improving; 5% had documented contraindications; the remaining 2% were a combination of patient refusal and missed opportunities. Interestingly, all missed opportunities resulted in discharge to SNF or AR. It appears, based on these data, clinical decisions made to withhold Activase in the setting of rapidly resolving symptoms did not result in further in-patient care in the majority of patients.

Conclusions:
Based on these data, nearly half of all strokes are discharged back into the community; an evaluation of available community and outpatient services may be beneficial. Further evaluation of potential barriers and opportunities to expand access to acute rehabilitation may be warranted. An evaluation of patients discharged to SNF may also be valuable to ensure discharge to most appropriate level of care to ensure best outcomes
Abstract WMP13: Latest Generation of Flat Detector CT as a Periinterventional Diagnostic Tool: A Comparative Study with Multidetector CT
Authors: Leyhe Johanna Rosemarie , Tsogkas Ioannis , Hesse Amelie Carolina , Knauth Michael , Psychogios Marios-Nikos
Published: June 2021

Background and Purpose:
Flat detector CT has been used as a periinterventional diagnostic tool in numerous studies with mixed results regarding image quality and detection of intracranial lesions. We compared the diagnostic aspects of the latest generation flat detector CT to a standard multidetector CT.

Materials and Methods:
One hundred and two patients were included in our retrospective study. All patients had undergone interventional procedures; flat detector CT was acquired periinterventionally and compared to a postinterventional multidetector CT regarding the depiction of ventricular/subarachnoidal spaces, the detection of intracranial hemorrhage and the delineation of ischemic lesions by using an ordinal scale. Ischemic lesions were quantified with the Alberta Stroke Program Early CT score on both exams. Two neuroradiologists of various experience grades and a medical student scored the anonymized images, blinded to clinical history.

Results:
The two methods were diagnostic equal in evaluating the ventricular system and the subarachnoidal spaces. Subarachnoidal, intraventicular and intraparenchymal hemorrhages were detected with a sensitivity of 95%, 94%, 100% and specificity of 97%, 97% and 99% respectively using flat detector CT. Grey-white differentiation was feasible in the majority of flat detector CT scans and ischemic lesions were detected with a sensitivity of 71% on flat detector CT, compared to multidetector CT scans. Alberta Stroke Program Early CT score values correlated highly with a correlation coefficient of r=0,78.

Conclusion:
The latest generation of flat detector CT is a reliable tool for the detection of intracranial hemorrhage and extended ischemic lesions. Flat detector CT acquired with angiography systems could be increasingly used in acute stroke diagnostics (so called one stop imaging) with a massive impact in door to groin times.
Abstract WMP14: Accuracy of Smartphone-based Evaluation of Large Vessel Occlusion on CTA
Authors: Hidlay Douglas T , McTaggart Ryan , Yaghi Shadi , Dibiasio Eleanor , Tung Eric , Baird Grayson , Tung Glenn , Jayaraman Mahesh
Published: June 2021

Introduction:
Since mechanical thrombectomy was established as the gold standard for treatment of stroke caused by an emergent large vessel occlusion (ELVO), comprehensive stroke centers have worked to streamline their workflow and minimize time-to-intervention; the ability to rapidly review CT angiography (CTA) is one hurdle in that process. To that end, we evaluated the diagnostic accuracy and confidence in review of CTA of the head and neck for ELVO via a smartphone-based application (LifeImage) as compared to review on a PACS workstation.

Methods:
Seventy-six head and neck CTA studies performed for potential stroke from one comprehensive and seven primary stroke centers were independently reviewed remotely on smartphone by two blinded neurointerventional radiologists in actual-use circumstances. The presence and location of large vessel occlusion(s), diagnostic quality, and confidence in interpretation were recorded. Comparison was made to blinded review of these studies on a PACS workstation performed at a delayed interval. Kappa statistics were calculated to evaluate intra- and inter-observer reliability.

Results:
Over 76 studies, occlusion of the M1 segment was demonstrated in 14 (18%); carotid artery in 2 (3%); tandem carotid and M1 in 2 (3%); basilar artery in 2 (3%); and no large vessel occlusion in 56 (73%). There was complete agreement between CTA interpretations on smartphone and on PACS with excellent intra- and inter-observer reliability (Table 1). No ELVOs were missed on smartphone review of these studies.

Conclusion:
In actual-use circumstances, experienced neurointerventional radiologists are able to utilize a smartphone application to diagnose an ELVO on CTA as accurately as on a PACS workstation with similar levels of confidence. These findings support the use of mobile electronic devices by stroke networks to rapidly triage patients for mechanical thrombectomy.
Abstract WMP23: Enhanced Collaterals in Patients with Large Vessel Stroke from Intracranial Atherosclerosis: An Automated CT Perfusion-based Study
Authors: Haussen Diogo C , Bouslama Mehdi , Dehkharghanii Seena , Bowen Meredith , Faggard Jason , Grossberg Jonathan A , Moyer Larry , Frankel Michael R , Nogueira Raul G
Published: June 2021

Background and Purpose:
Patients with intracranial atherosclerotic disease (ICAD) are believed to have enhanced collateral flow. We have anecdotally perceived that large vessel occlusion acute strokes (LVOS) patients due to ICAD have more benign automated CT perfusion (CTP) defect profiles, potentially reflecting improved collateralization in comparison to embolic LVOS.

Methods:
Retrospective review of a prospectively collected interventional stroke database from Sep 2010-Mar 2015. Patients were dichotomized into ICAD vs. other etiology. Patients with a technically adequate CTP and an intracranial ICA, MCA M1 or M2 occlusion were included. Tandem extracranial carotid occlusions were excluded due to the known effects on bolus dispersion and delay of bolus passage. Ischemic core (relative CBF<30%) and perfusion defects were estimated by RAPID automated CTP. The primary endpoint was to compare the ratio of CTP Tmax>4s (“benign oligemia”) / Tmax>6s (“territory at risk”) between the two groups.

Results:
A total of 250 patients fit inclusion criteria, of whom 21 (8%) were classified as ICAD and 229 had other stroke etiologie. Baseline characteristics were similar between the two groups, except for higher hemoglobin A1c levels (p<0.01), higher baseline systolic blood pressure (p<0.01); and lower rates of atrial fibrillation (p<0.01) in the ICAD group. There were no differences in ischemic core (p=0.51), perfusion defect Tmax>4s (p=0.86), Tmax>6s (p=0.57) and Tmax>10s (p=0.17). ICAD patients had a median ratio of Tmax>4s/ Tmax>6s of 2. A Tmax>4s/ Tmax>6s ratio≥2 showed a specificity of 83% and a sensitivity of 52%, and was more common in the ICAD group (p=0.1). Multivariate logistic regression analysis revealed that higher rates of Tmax>4s/ Tmax>6s ratio≥2 (OR 3.36 95% CI 1.05-10.71, p=0.04), lower rates of atrial fibrillation(OR 0.17 95% CI 0.04-0.86, p=0.03), and higher systolic pressure (OR 1.03 95% CI 1.01-1.05, p=0.002) were independently associated with ICAD.

Conclusion:
A RAPID CTP Tmax>4s/ Tmax>6s ratio≥2 profile is an independent and highly specific indicator of underlying ICAD LVOS etiology.
Abstract WMP29: Trends of Angioplasty for Cerebral Vasospasm in Endovascularly Treated Aneurysmal Subarachnoid Hemorrhages
Authors: Mehta Tapan V , Patel Smit , Hussain Mohammed , Narwal Priya , Mirtchev Dimitre , Nouh Amre , Ollenschlegher Martin , Kureshi Inam
Published: June 2021

Introduction:
Treatment of the sequale following aSAH such as vasospasm has evolved to include different options ranging from endovascular angioplasty to administration of intra-arterial calcium channel blockers and permissive hypertension. Our study examines trends of angioplasty for cerebral vasospasm usage in endovascularly treated aSAH.

Methods:
We used Nationwide Inpatient sample data from 2002 to 2012. ICD9 codes 430, 431 and 432 in conjunction with ICD9 procedure code 39.72 (endovascular repair/embolization of head and neck vessel) were used to identify endovascularly treated aSAH patients (Excluding ICD9 747.81 - cerebral AVM). Cerebral vasospasm treated with angioplasty was identified with ICD procedure code 00.62 and 39.50. Patients requiring external ventricular drain (EVD) were also identified to stratify higher severity of aSAH. Comorbidities were controlled using Charlson’s Index. The population was divided into Age <50 and Age >=50 groups to understand differences in angioplasty trends in these groups, as there is evidence of increased risk of cerebral vasospasm in patients with age less than 50 years. Trend of angioplasty were evaluated using a multivariate model with survey logistics using SAS 9.2.

Results:
We identified 9,856 hospitalizations with 62.6% in Age > 50 and 37.4% in Age < 50 group. Overall 4.04% in Age >50 and 5.80% in Age <50 group required angioplasty. In Age >50 group, Increasing year from 2002 to 2012 predicted decreased requirement of angioplasty with Odds Ratio(OR) of 0.935 (95% Confidence Interval (CI) 0.879-0.995, p=0.03) after controlling for increasing age, Chanrlson’s co-morbidity index and EVD placement; however the same trend was not statistically significant for Age < 5o (OR - 0.967, 95%CI 0.917-1.020, p=0.2150).

Conclusion:
Decreasing trend of angioplasty for aSAH related cerebral vasospasm was observed during the past decade in population with age more than 50 years in our study. Advances in endovascular care such as administration of intra arterial calcium channel blockers as well as enhanced neuro-critical management of vasospasm may have contributed to a decrease in the trend of angioplasty treatment of vasospasm after aSAH.
Abstract WMP31: Integration of MRA and CTA for Brain Aneurysm Follow up
Authors: Chien Aichi , Ruan Dan
Published: June 2021

Introduction:
Because MR does not involve ionizing radiation and may be used without contrast, recently there has been a trend towards monitoring aneurysms primarily with MRA and then use CTA as needed. Our goal is to establish a machine learning technique for aneurysm evaluation that can generate images with comparable image quality to CTA based on time of flight (TOF) MRA.

Methods:
TOF MRA and CTA images acquired less than 2 weeks apart were used. A set of clinical TOF MRA and CTA were used for training and five additional sets were used for testing. TOF was obtained with gradient recalled echo (TR = 33ms, TE=3.2ms) on 1.5T scanners. CTA scans were acquired using 64 slice scanner (pitch=1.0, reconstruction kernel H30f). During the training stage, cross modality registration was performed to maximize mutual information between TOF and the corresponding CTA. To generate machine learning angiography (MLA) images, the input TOF were divided into sliding patches and their coefficient was estimated and used as an input to the neural network to infer voxelwise CTA values. Figure: images used for learning (aneurysm, right ICA; greyscale, CTA; red, TOF MRA).

Results:
The MLA images enhanced visibility of artery structures from the original TOF. High geometric agreement was achieved between MLA images and CTA. In comparison to CTA, MLA images had sub-mm Hausdorff distance and pairwise distance of 0.24±0.12mm for all aneurysm localities for all tested image sets. With an aneurysm growth threshold defined as size change more than 0.6 mm in CTA, MLA provides sufficient resolution for cross modality follow up comparisons.

Conclusions:
This pilot study has demonstrated promise to enhance artery visibility and interpretation from MRA using machine learning techniques to yield CTA-like images. The performance of the current method is affected by the dependence of flow enhancement with respect to imaging planes in TOF and requires consistent imaging protocols for training and testing subjects.
Abstract WMP33: Peri-operative Dual Antiplatelet Therapy for the Coil Embolization of Unruptured Brain Aneurysms: The Efficacy and the Side Effect
Authors: Sakuta Kenichi , Yuki Ichiro , Ishibashi Toshihiro , Kaku Shogo , Sasaki Yuichi , Murayama Yuichi
Published: June 2021

Backgrounds:
Optimal dose and duration of antiplatelet therapy before / after the coil embolization of unruptured aneurysm has not been established, yet. The dual antiplatelet therapy (DAPT) using aspirin and clopidogrel started 3 to 7 days before operation has been a commonly used antiplatelet protocol, although few studies have done to evaluate the relationship between the duration of the pre-operative DAPT and its efficacy / side effects. In the present study, the different durations of the pre-operative DAPT and their related “efficacy / side effect” was retrospectively analyzed.

Method:
A total of 232 unruptured brain aneurysm patients (male, n=62; median age, 61 y) who underwent coil embolization were enrolled in this study. Fifty-two (22%) patients underwent stent assisted coil embolization. The patients were categorized into 3 different groups depending on the duration of the DAPT: Group A (within 3days), Group B (4-6 days) and Group C (7 days or longer). The platelet aggregation profiles are evaluated on the day of procedure. Post-operative MRI, the neurological findings and the peri-operative hemorrhagic events between the 3 groups were compared.

Results:
Diffusion weighted image (DWI) performed the day after the operation showed that 169 (73%) patients had any high intensity lesion in the ipsilateral perfusion area of the treated artery, and 8 (3%) represented symptomatic infarction. The both adenosine diphosphate (ADP) and collagen aggregation were significantly decreased in the group of longest DAPT period (vs Group A (ADP; 45% vs 15%,
P
<0001, collagen 99% vs 90%
P
=0.008), vs Group B (ADP; 45% vs 27%,
P
=0.032, collagen 99% vs 94%,
P
=0.137)). The symptomatic infarction after operation tended to decrease with longer DAPT period without statistical significance. The rate of hemorrhagic complication was not increased by the longer DAPT period during the observation period.

Conclusion:
Longer DAPT period significantly reduced both the ADP and collagen aggregation. The rate of symptomatic thromboembolic event tended to decrease with longer DAPT period without statistical significance. With increased number of patient, longer DAPT protocol may reduce the thromboembolic event without increasing the hemorrhagic complication rate.
Abstract WMP34: Low Yield of Further Angiographic Follow-up in Adequately Occluded Aneurysms After Flow Diversion
Authors: Chalouhi Nohra , Barros Guilherme , Tjoumakaris Stavropoula , Kumar Ayan , Lang Michael , Rosenwasser Robert , Jabbour Pascal
Published: June 2021

Background:
Aneurysm recurrence after coil therapy remains a major shortcoming in the endovascular management of cerebral aneurysms. Flow diversion has emerged as a promising treatment for intracranial aneurysms. The safety and efficacy of this new technology is under investigation. The current study assesses the yield of further angiographic follow-up in aneurysms that have achieved adequate occlusion after treatment with the Pipeline Embolization Device (PED).

Methods:
Inclusion criteria were as follows: 1) treatment of one or more aneurysms with the PED, 2) available short-term (<12 months) follow-up digital subtraction angiography (DSA), 3) complete (100%) or near-complete (>95%) occlusion on short-term follow-up DSA, and 4) available further angiographic follow-up (DSA or MRA).

Results:
A total of 175 patients matching the inclusion criteria were identified. Aneurysm size was 9.0 mm on average. Mean angiographic follow-up was 23.4 months. On short-term follow-up DSA images, 154 (88%) had complete aneurysm occlusion and 21 (12%) had near-complete occlusion. Seven patients (4%) had further DSA follow-up alone, 39 patients (22%) had further DSA and MRA follow-up, and 129 patients (74%) had further MRA follow-up alone. On further angiographic follow-up (DSA or MRA), no patient had a decrease in the degree of aneurysm occlusion (recurrence) or required retreatment. Of the 21 patients with near-complete occlusion on initial DSA images, 5 patients (24%) progressed to complete aneurysm occlusion on further angiographic follow-up. No patient had evidence of new in-stent stenosis on further angiographic follow-up.

Conclusion:
In this study, the diagnostic yield of repeat angiography in adequately occluded aneurysms with the PED was very low. Based on these findings, we do not recommend further angiographic follow-up once aneurysms have achieved adequate occlusion with the PED.
Abstract WMP36: Inhibition of the Endothelial Shear Stress Sensor, P2x4 Purinoceptor Drastically Reduces Cerebral Aneurysm Formation
Authors: Fukuda Shunichi , Fukuda MIyuki , Ando Joji , Yamamoto Kimiko , Tuskahara Tetsuya , Ito Yuki , Hasegawa Koji
Published: June 2021

Background and purpose:
Although the assumption that wall shear stress-related hemodynamics is closely involved in cerebral aneurysm formation is now widely accepted, direct evidence still remains to be presented. Here, we examine a role of shear stress in cerebral aneurysm development, focused on a vascular endothelial shear sensor, P2X4 purinoceptor.

Methods:
P2X4 knockout mice and wild type mice were subjected to cerebral aneurysm-generating surgery with ligation of unilateral common carotid artery and renal hypertension. Damage to the internal elastic lamina, early phase aneurysm development, and the incidence of aneurysm induction were examined by light microscope. The expression of biochemical contributors to aneurysm formation was immunohistochemically examined. Additionally, the P2X4 purinoceptor inhibitor, paroxetine (10mg/kg/day) was administered to Sprague-Dawley rats after aneurysm-inducing surgery, and the incidence of aneurysm formation was examined.

Results:
Damage to the internal elastic lamina and the frequency of CA induction were significantly diminished in P2X4 knockout mice compared to control wild-type mice after CA-inducing surgery (
p
=0.027 and 0.018, respectively). Expression levels of known contributors to aneurysm formation, iNOS, MCP-1, cathepsin L, and COX-2, were immunohistochemically weakened in P2X4 KO mice compared to wild-type mice. Moreover, paroxetine significantly attenuated the incidence of induced aneurysms in rats (
p
=0.031).

Conclusions:
Disruption of the endothelial shear stress sensor, P2X4 purinoceptor drastically reduces cerebral aneurysm formation, suggesting that shear stress-related hemodynamics initiates cerebral aneurysm formation. The P2X4 purinoceptor inhibitor paroxetine, which is also prescribed to human as an antidepressant, may be a potential clinical prophylactic agent against cerebral aneurysm formation.
Abstract WMP58: Blacks Have Higher Risk of 1-Year Recurrent Ischemic Stroke: An Analysis of White and Black Medicare Beneficiaries 1999-2013
Authors: Albright Karen C , Huang Lei , Blackburn Justin , Howard George , Mullen Michael , Bittner Vera , Muntner Paul , Howard Virginia
Published: June 2021

Introduction:
Blacks have a higher incidence of stroke compared with whites. Most stroke survivors in the United States are 65 years and older but few data are available on racial differences in recurrent stroke risk in this age group.

Methods:
We conducted a retrospective cohort of Medicare beneficiaries in the 5% sample from 1999-2013 to compare 1-year recurrent stroke risk in older black and white Americans following hospitalization for ischemic stroke. We studied beneficiaries with Medicare fee-for-service coverage for 182 days before the index stroke hospitalization with no claims for stroke-related events. Patients were divided into two age groups (66-74, 75 years and above) and stratified into 3 calendar periods (1999-2001, 2002-2006, 2007-2013) allowing for implementation of secondary stroke prevention trial findings (PROGRESS, 2001; SPARCL, 2006). Hazard ratios for recurrent ischemic stroke comparing blacks to whites were calculated with adjustment for demographics, risk factors, and the competing risk of death.

Results:
Of 128,789 ischemic stroke patients (mean age 80 years [SD 8], 11.1% black, 60.4% male), 7.8% of whites and 11.0% of blacks had a recurrent ischemic stroke overall (Table 1). For each time period, blacks had a higher risk of recurrent stroke compared with whites (Figure 1). This disparity increased over time among patients age 66-74 years (p=0.038) but no trend was present for those 75 years and above (p=0.301).

Conclusion:
The risk of stroke recurrence among older Americans hospitalized for ischemic stroke is higher for blacks than whites, regardless of age group.
Abstract WMP60: Association Between Liver Cirrhosis and Stroke in a Nationally Representative Cohort
Authors: Parikh Neal S , Navi Babak B , Schneider Yecheskel , Kamel Hooman
Published: June 2021

Introduction:
Liver cirrhosis is characterized by a coagulopathy associated with both hemorrhagic and thrombotic complications. However, the risk of stroke - hemorrhagic and ischemic - in patients with cirrhosis has not been rigorously assessed.

Methods:
We performed a retrospective cohort study of Medicare beneficiaries ≥66 years of age using a 5% sample of inpatient and outpatient claims from 2008-2014. Our predictor was liver cirrhosis, defined by presence of at least two
ICD-9-CM
inpatient or outpatient claims for liver cirrhosis or its complications, a validated algorithm previously used to study cirrhosis in Medicare beneficiaries. The primary outcome was stroke, and the secondary outcomes were ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Outcomes were defined by validated
ICD-9-CM
algorithms. Patients were censored at the time of an outcome, death, or on December 31, 2014. We used survival analysis to compare stroke incidence in patients with and without liver cirrhosis. Cox proportional hazards analysis was used to evaluate the association between cirrhosis and stroke while adjusting for demographics and established stroke risk factors.

Results:
Among the 1,564,277 beneficiaries in our sample, we identified 10,512 (0.7%) patients with liver cirrhosis. The mean age of patients with cirrhosis was 74.1 (±6.5) years. Over a median follow-up of 5 years, 76,195 patients were hospitalized with a stroke. The incidence of stroke was 1.9% (95% confidence interval [CI], 1.7-2.1%) per year in patients with cirrhosis and 1.1% (95% CI, 1.1-1.1%) per year in patients without cirrhosis. After adjusting for demographics and vascular risk factors, patients with cirrhosis experienced a higher risk of stroke (hazard ratio [HR], 1.4; 95% CI, 1.2-1.5); however, associations appeared more robust for intracerebral hemorrhage (HR, 2.2; 95% CI, 1.7-2.8) and subarachnoid hemorrhage (HR, 2.0; 95% CI, 1.2-3.1) than for ischemic stroke (HR, 1.3; 95% CI, 1.1-1.4).

Conclusions:
We found that liver cirrhosis was associated with an increased risk of stroke, particularly hemorrhagic stroke. Our results build on recent work investigating the hemorrhagic and thrombotic complications of liver cirrhosis outside of the portal circulation.
Abstract WMP64: Utility of Left Atrial Abnormality on Admission Electrocardiography in Acute Ischemic Stroke
Authors: Sugiyama Yukio , Ohara Nobuyuki , Watanabe Kotaro , Kobayashi Junya , Takahashi Daisuke
Published: June 2021

Introduction and Hypothesis:
Clinical categorization of ischemic stroke is very important to select the antithrombotic therapy for preventing the recurrent stokes. However, about 25% of ischemic stroke is the stroke for undetermined cause, termed as cryptogenic stroke. Recently, proactive detecting of paroxysmal atrial fibrillation (PAF) in cryptogenic stroke has gained attention. P-wave terminal force in lead V1 (PTFV1) of electrocardiography (ECG) is a specific indicator of left atrial abnormality. In this study, we tested PTFV1 for the utility of PAF detection and further clinical categorization in acute ischemic stroke.

Methods:
One hundred forty eight consecutive acute ischemic stroke patients were admitted to our hospital from September 2014 to March 2016. We included 105 patients (mean age 72.8±13.4 years), who had sinus rhythm on admission 12-lead ECG without atrial fibrillation, or cardiac pacing. PTFV1 (mmхsec) of participants was assessed, and had analyzed the association with PAF detection in a 24-hour ECG monitoring and clinical categories of ischemic stroke.

Results:
PTFV1 was significantly higher in the patients with PAF (n=11) than in those without PAF (0.049±0.024 vs 0.031±0.027; p<0.05). Multiple logistic regression analysis revealed that PTFV1 was an independent predictor for PAF detection (odds ratio, 1.46; 95% confidence interval, 1.02-2.08; p<0.05). According to the clinical categorization, PTFV1 of cardioembolic stroke (0.061±0.022) was significantly higher, compared to lacunar stroke (0.018±0.019; p<0.01), atherothrombotic stroke (0.035±0.026; p<0.05), and cryptogenic stroke (0.031±0.029; p<0.05). The proportion of patients with left atrial abnormality defined by PTFV1 (≧0.04), was 10 out of 11 (91%) for cardioembolic stroke, and 10 out of 27 (37%) for cryptogenic stroke.

Conclusions:
PTFV1 on admission ECG in acute ischemic stroke was a strong predictor for PAF detection and cardioembolic stroke diagnosis. Extended ECG monitoring may be useful in cryptogenic stroke with left atrial abnormality defined by PTFV1.
Abstract WMP68: Evidence of Cardiac Stress in Acute Cerebral Venous Thrombosis
Authors: Johansen Michelle C , Gottesman Rebecca , Urrutia Victor
Published: June 2021

Background:
Plasma cardiac troponin (cTnI) elevation has been associated with death after ischemic stroke and elevation has been theorized to result from an exaggerated sympathetic response. To our knowledge, no investigation into the cardiac effects of cerebral venous thrombosis (CVT) has been conducted. We hypothesized that acute CVT could result in similar cardiac stress manifesting as electrocardiogram (ECG) changes or cTnI elevation.

Methods:
In this retrospective cohort study of all consecutive patients admitted to Johns Hopkins Hospital from 2005-2015 with CVT by ICD9/10 code, patient data (sex, race, risk factors, CVT location/number, venous bleed/stroke, cTnI, ECG) were obtained from hospital records.

Results:
Of 81 patients identified with CVT, 53 (66%) had clot in at least one vein and had available ECG data; this group constituted our study population. Included patients had an average age of 41 years (range 1-80); 71% were white and 66% female. The left transverse sinus was most commonly involved (47%) and 66% of patients had >2 clots. 22(41%) had cTnI elevation, defined as >0.06. Odds of cTnI elevation increased per each additional vein involved (age-adjusted OR 2.64, 95%CI 1.14, 6.13] Of those with deep clots (deep veins, straight sinus; n=8), 37.5% had cTnI elevation compared to 4.44% without deep clots (p=0.02). The mean cTnI of those individuals with venous infarct (n=15) was higher than those without (0.14 vs 0.02, p=0.009) but lost significance after adjusting for age/race. cTnI elevation was not associated with venous hemorrhage. No significant association was found between ECG parameters and clot number/venous infarct.

Conclusions:
Clots in multiple veins and deep veins increased odds of cTnI elevation in a retrospective cohort of acute CVT patients irrespective of age and race. The cardiac effects of acute CVT should be recognized and further investigated to elucidate pathophysiology, and significance.
Abstract WMP70: Enhancement of Atherosclerosis Prediction by Interaction of Circulating mir-212 with Hemoglobin A1c, Lipoprotein(a), and High-density Lipoprotein Cholesterol
Authors: Jeong Hye Seon , Kim Jeeyeon , Lee Seo Hyun , Hwang Junha , Shin Jong Wook , Lee Sukhoon , Kim Jei
Published: June 2021

Background and Objectives:
The present study aimed to identify atherosclerosis-related circulating miRNAs and to evaluate their interaction with other cardiovascular risk markers to improve the prediction of atherosclerosis presence.

Methods:
We used miRNA profiling to identify atherosclerosis-related miRNAs using serum of 8 non-atherosclerotic and 7 severe atherosclerotic ischemic stroke patients. Expression of the target miRNAs identified was validated in 38 non-atherosclerotic and 37 atherosclerotic patients. Associations of the target miRNAs with other cardiovascular risk markers to predict atherosclerosis presence were analyzed using forward logistic regression analysis. Interactions of miRNAs with risk markers in the prediction of atherosclerosis presence were analyzed using accuracy and discrimination analysis.

Results:
miR-212, -30c, -372, -454, and, -744 were identified as atherosclerosis-related miRNAs. Only miR-212 showed a significant increase in expression in atherosclerotic patients of the validation population. Of various established markers tested, hemoglobin A1c, high-density lipoprotein cholesterol, and lipoprotein(a) were independently related with atherosclerosis presence in the validation population. miR-212 significantly increased the accuracy (three markers, 78.55%; three markers+miR-212, 84.6%) and area under the receiver operating characteristic curve (three markers, 0.8258; three markers+miR-212, 0.8646) of atherosclerosis prediction by the three existing markers.

Conclusion:
We identified circulating miR-212 as a novel marker of atherosclerosis. miR-212 synergistically enhanced the prediction of atherosclerosis-presence in combination with hemoglobin A1c, high-density lipoprotein cholesterol, and lipoprotein(a). Thus, miR-212 is expected to improve the prediction of atherosclerosis using peripheral blood of patients.
Abstract WMP71: Moyamoya-atherosclerosis Syndrome: Clinical and High-resolution Magnetic Resonance Imaging Features
Authors: Duan Lian , Xu Wei-Hai , Han Cong
Published: June 2021

Introduction:
The diagnosis in the patients with angiographic moyamoya findings and atherogenic risk factors is challenging. In this study, we try to incorporate high-resolution magnetic resonance imaging (HRMRI) into the diagnostic process of intracranial atherosclerosis associated moyamoya syndrome.

Methods:
From March 2013 to March 2014, HRMRI was consecutively performed on adult patients with angiographic moyamoya. The patients were classified as moyamoya - plaques (MMD-P) if a plaque could be identified or as moyamoya - no plaques (MMD-NP) if a plaque could not be identified. The angiography, HRMRI findings and atherogenic risk factors of these patients were analyzed.

Results:
Fifty-one patients (mean age 39±9, 20 males) were enrolled. On traditional angiography, probable intracranial atherosclerosis was identified in 5 patients, no definite diagnosis in 12 patients, and moyamoya disease in 34 patients. On HRMRI, 15 out of 32 patients with risk factors and 4 out of 19 patients without risk factors were found to have plaques and were diagnosed as MMD-P, while the other 32 patients were diagnosed as MMD-NP. The MMD-P patients were more likely to be older and male and were less likely to have cerebral hemorrhage and a history of disease progression.

Conclusions:
Our study suggests that HRMRI can help diagnose intracranial atherosclerosis more accurately in moyamoya disease patients with atherogenic risk factors. The distinct clinical features between MMD-P and MMD-NP patients suggest different underlying pathophysiology and therefore potentially different treatment strategies.
Abstract WMP72: Peptide Composition of Stroke Causing Emboli Correlate With Serum Predictors of Atherosclerosis
Authors: Rao Neal M , Capri Joseph , Cohn Whitaker , Abdaljaleel Maram Y , Restrepo-Jimenez Lucas , Gornbein Jeffrey A , Yong William H , Liebeskind David S , Whitelegge Julian P
Published: June 2021

Introduction:
The specific protein composition of stroke-causing emboli is unknown. Because ischemic stroke has a varied etiology, it is possible that the composition of the thrombus from which an embolus originated will have distinctive molecular characteristics reflective of the underlying pathophysiology. In this study, we used mass spectrometry to evaluate the protein composition of retrieved emboli from patients with differing stroke etiologies and correlated the protein levels to serum predictors of atherosclerosis.

Methods:
Emboli from 20 consecutive acute stroke patients were retrieved by embolectomy during routine stroke care. Thrombus proteins were extracted, digested and multidimentional fractionation of peptides was performed. Fractionated peptides underwent nano-liquid chromatography with tandem mass spectrometry. Spectra were searched using Mascot software in which results with p<0.05 (95% confidence interval) were considered significant and indicating identity. The results were correlated to A1C, LDL, and ESR taken on admission.

Results:
Demographics: 55% had atrial fibrillation, 20% had significant proximal vessel atherosclerosis, 10% were cryptogenic, and three had other identified etiologies (left ventricular thrombus, dissection, endocarditis). Eighty-one common proteins (eg hemoglobin, fibrin, actin) were found in all 20 emboli. Serum LDL levels correlated with Septin-2 (r
s
=0.78, p=0.028), Phosphoglycerate Kinase 1 (r
s
=0.75, p=0.036), Integrin Alpha-M (r
s
=0.68, p=0.033) and Glucose-6-phosphate dehydrogenase (r
s
=0.63, p=0.05). Septin-7 levels inversely correlated to ESR (r
s
= -0.84, p=0.01). No significant protein correlations to A1C were found.

Conclusion:
To our knowledge, this study is the first mass spectrometry analysis of thrombi retrieved from acute stroke patients and the first to correlate the thrombus proteome to clinical features of the patient. Notably, we found proteins associated with inflammation (eg Integrin Alpha–M) in emboli from patients with high LDL. Although these findings are tempered by a small sample size, we provide preliminary support for the feasibility of utilizing proteomic analysis of emboli to discover proteins that may be used as markers for stroke etiology.
Abstract WMP77: Combination of Metabolic and Transcriptional Profiling Identifies Pentose Phosphate Pathway Activation by Heat Shock Protein 27 Phosphorylation During Cerebral Ischemia
Authors: Yamamoto Yusuke , Hosoda Kohkichi , Imahori Taichiro , Irino Yasuhiro , Shinohara Masakazu , Tanaka Jun , Nakai Tomoaki , Sato Naoko , Kohmura Eiji
Published: June 2021

Objectives:
The metabolic pathophysiology of ischemic stroke remains poorly understood. We performed a comparative omics analysis to identify the effects of cerebral ischemia on metabolism of cerebral cortex in the rat model with middle cerebral artery occlusion (MCAO).

Methods:
MCAO was induced with suture occlusion technique. After the desired period of MCAO (30, 60, 120min), the rats were sacrificed. Tissue samples from the ischemic lesion were collected. Sham operated rats were treated in the same way except MCAO. Water-soluble metabolites were extracted and measured by gas-chromatography/mass-spectrometry (GC/MS). The obtained data were analyzed using multivariate statistics to explore metabolic pathways involved in ischemia. The associated metabolic enzymes were investigated with real-time polymerase chain reaction (RT-PCR) and Immunoblot analysis.

Results:
Metabolic profiling by GC/MS analysis showed clear separation between the ischemia and control group (Figure A, B). The decrease of fructose 6-phosphate and ribulose 5-phosphate suggested enhancement of the pentose phosphate pathway (PPP) during cerebral ischemia. Transcriptional profiling by microarray hybridization indicated that Toll-like receptor and mitogen-activated protein kinase (MAPK) signaling pathway were upregulated during cerebral ischemia. In relation to PPP, upregulation of heat shock protein 27 (HSP27) was observed in the MAPK signaling pathway and was confirmed through RT-PCR. Immunoblotting showed a slight increase in HSP27 protein expression and a marked increase in HSP27 phosphorylation (FigureC). Corresponding upregulation of glucose 6-phosphate dehydrogenase (G6PD) activity and an increase in the NADPH/NAD+ ratio were also observed (Figure D, E).

Conclusions:
G6PD activation via ischemia-induced HSP27 phosphorylation may be part of an endogenous antioxidant neuroprotection mechanism during the earliest stages of ischemia.
Abstract WMP9: Endovascular Thrombectomy Impact in the First Three “Golden” Hours
Authors: Sarraj Amrou , Veznedaroglu Erol , Budzik Ronald F , English Joey D , Baxter Blaise W , Bartolini Bruno M , Krajina Antonin , Shields Ryan D , Nogueira Raul G , Gupta Rishi , Spiegel Gary R , Savitz Sean I , McCullough Louise D , Farrell Christine M , Liebeskind David S
Published: June 2021

Background:
Endovascular thrombectomy (EVT) substantially increases the likelihood of good outcome in acute ischemic strokes due to large vessel occlusion (LVO). Expediting EVT to achieve faster reperfusion is an important factor that correlates with good outcome. Ultra-early intervention in the first 3 “golden” hours from onset was not well characterized in recent trials.

Objective:
We sought to assess the impact of early treatment within the first 3 hours on clinical outcomes in large, real life, world-wide practice.

Methods:
We analyzed a multicenter international prospective cohort study of LVO patients treated with stent retriever thrombectomy (TREVO Registry) between11/2013 and 4/2016. We stratified patients based on treatment time, onset to groin puncture (GP), into 3 groups: 0-3, 3-6, >6 hrs. 90 day mRS was the primary outcome (0-2 good outcome). Logistic regression modeling was performed to evaluate the impact of treatment within the golden 3 hours on outcomes and to determine the independent factors associated with EVT initiation within 3 hours.

Results:
In the 905 patients, GP occurred in: 23.1% 0-3 hrs, 44.3% 3-6 hrs and 32.6% >6 hrs. Table 1 shows similar baseline characteristics among the groups. Patient-level predictors of treatment within 3 hrs were age (aOR 1.1 per decade of age ≥18) and good ASPECTS (aOR 1.2 per point). No hospital-level predictors of early treatment were found. Patients treated within 3 hrs have a higher likelihood of good outcome as compared to those treated >3 hrs (aOR 2.0, 95% CI 1.4-2.9;
p
<0.001) after adjustment for age, NIHSS, IV tPA and mTICI ≥2b (Table 2). No differences were found in mortality and sICH. Treatment in the golden hours had the highest impact on excellent outcome rates (mRS 0-1) (Fig 1).

Conclusion:
Early thrombectomy of LVO strokes, within the first three hours provides the highest impact compared with later time windows. Streamlining processes to deliver rapid intervention within 3 hours would improve clinical outcomes.