bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP13: The Rate of Hemicraniectomy Utilization for Acute Ischemic Stroke Patients Undergoing Endovascular Treatment is Decreasing in the United States
Authors: Chaudhry Saqib A , Hassan Ameer E , Afzal Mohammad R , Riaz Riaz , Rahman Haseeb , Malik Ahmed , Jani Vishal , Razak Anmar , Qureshi Ihtesham A , Qureshi Adnan I
Published: July 2021

Background and Purpose:
Hemicraniectomy is carefully selected for patients with acute ischemic stroke in whom endovascular treatment has failed to prevent adverse outcomes of large hemispheric stroke. We evaluated trends in the utilization of hemicraniectomy in patients who underwent endovascular therapy according to the availability of three generations of thrombectomy devices and analyzed the associated rates of death and disability among them over a nine year period.

Methods:
We obtained data for patients admitted to hospitals in the United States from 2004 to 2012 with a primary diagnosis of ischemic stroke using a large national database. We determined the rate and pattern of hemicraniectomy utilization, and associated in-hospital outcomes of endovascular treatment among ischemic stroke patients. Outcomes were compared between three time periods: 2004-2006 (post MERCI), 2007-2009 (post Penumbra) and 2010-2012 (post Solitaire stent retriever) approvals.

Results:
Of the 6,021,636 patients admitted with ischemic stroke, 28,956 (0.48%) underwent endovascular treatment. Of the patients who underwent endovascular therapy, 2,219 (7.6%) required subsequent hemicraniectomy. There was a 7 fold decrease in the utilization of hemicraniectomy in these patients between 2004 and 2009 (25.6% in 2004 vs. 3.5% in 2009, p < 0.001) with a yearly trend towards decreased utilization of hemicraniectomy [OR 0.7, 95% CI 0.6- 0.8, p <.0001].

In multivariate logistic regression analysis there was a reduction in the rate of in hospital mortality of the 2007-2009 and the 2010-2012 groups when compared to the 2004-2006 interval group (2007-2009, odds ratio (OR) 0.9, 95% confidence interval (CI) (0.7- 1.2) and 2010-2012, [OR 0.9, 95%CI 0.7- 1.1]). The rate of moderate to severe disability increased for patients treated during 2007-2009 and 2010-2012.

Conclusion:
In the last 9 years there has been a significant decrease in the utilization of hemicraniectomy in acute ischemic stroke patients who underwent endovascular treatment. Despite reduction in use of hemicraniectomy, the mortality rate in endovascularly treated patients have shown a reduction, but there was an increase in rate of moderate to severe disability.
Abstract WP138: Effects of Intensive Medical Management (IMM) and Encephaloduroarteriosynangiosis (EDAS) On VEGFA165a/b Ratios in Patients With Intracranial Atherosclerosis (ICASi
Authors: Gonzalez Nestor R , Liou Raymond , Ooi Yinn , Hinman Jason D , Rao Neal , Toscano Juan , Laiwalla Azim , Martin Neil , Liebeskind David S , Ali Latisha , Restrepo Lucas , Saver Jeffrey
Published: July 2021

Objective:
VEGFA isoforms 165a and 165b are pro and antiangiogenic, respectively. We aimed to evaluate the effects of IMM and EDAS in the VEGFA165a/b ratio in patients with ICAS.

Methods:
This is a prospective observational study of VEGFA165a and b in patients with stenosis greater than 70% due to ICAS. All patients received IMM. Patients with persistent symptoms underwent EDAS while maintaining IMM. Serum samples were collected at baseline, 1 week, 1, 3, and 6 months. VEGFA isoforms were quantified using multiplex sandwich ELISA. All samples were run in duplicate and accepted as valid if the intersample variability was less than 20%. A mixed model was built for the outcome variable VEGFA165a/b ratio using the predictor variables timepoint, treatment, and the interaction of time and treatment. The restricted maximum likelihood method was used to fit the model with random effects to account for the repeated measurements and intersubject variability.

Results:
A total of 72 patients were enrolled, of which 58 had IMM alone and 14 had EDAS. Mean age was 61.8 ± 12.3, 53% were females. The regression model demonstrated that there were no significant differences in the VEGFA165a/b ratio at baseline and 1 month after enrollment. Significant differences in VEGFA165a/b ratio were found at one week with higher levels in the surgical group (EDAS: 0.46 ± 0.22, IMM: 0.24 ± 0.07, p=0.03) and at 3 and 6 months with higher levels in the IMM group (3m: EDAS: 0.29 ± 0.14, IMM: 0.45 ± 0.20, p=0.03, 6m: EDAS:0.19 ± 0.11, IMM 0.37 ± 0.19 p=0.01).

Conclusion:
While the surgical event may well explain the early elevation of the VEGFA165a/b ratio one week after surgery, the elevation of a proangiogenic profile by the 3rd and 6th month in the IMM group is relevant. None of the patients in the IMM or EDAS groups had strokes at the last 6 months follow-up, and the peak (early for EDAS and at 3 and 6 months for IMM) of the VEGFA165a/b ratio may indicate a protective effect, averting stroke.
Abstract WP14: Identifying Potential Sliding Dichotomy Cutpoints for Thrombectomy Trials Using Baseline Age, Deficit Severity, and Core Lesion Volume
Authors: Tarpley Jason , Albers Greg , Mlynash Michael , Lansberg Maarten , Gornbein Jeffrey , Saver Jeffrey ,   The DEFUSE 2 investigators
Published: July 2021

Introduction:
In sliding dichotomy (SD) stroke trial analysis, each patient’s win criterion is tailored to their prognosis. SD is generally more powerful in detecting treatment effects than crude dichotomy (CD), in which the same win criterion is used for all patients. Potential SD cutpoints for endovascular therapy (ET) trials have not been well-delineated.

Hypothesis:
In ET patients, we tested whether the most informative cutpoints on the modified Rankin Scale (mRS) of global disability vary with age, deficit severity, and pretreatment core lesion volume.

Methods:
Among DEFUSE 2 trial patients, we compared 3 month outcomes between reperfusers (TICI 2b/3) and non-reperfusers (0-2a). Treatment effect profile maps delineated how prognostic subgroups influenced 5 dichotomizations of the 90D mRS.

Results:
Among 105 patients, mean age was 65.4 (±16.1), NIHSS 15.2 (±5.3), and median pretreatment DWI core lesion volume 15.4 ml (IQR 7-32.8). Treatment effect profile maps (Figure) showed better prognosis features tended slightly to increase the absolute difference in outcomes assessed by less disabled mRS cutpoints, including for younger vs older age, milder vs more severe NIHSS, and intermediate vs large core volume. However, crude dichotomization at mRS 0-3 performed well across all subgroups, indicating strong clustering of reperfusion effect across the population. Very small DWI core lesion patients showed a paradoxical effect, with greater treatment benefit at the more disabled mRS levels; high rates of good outcome among both recanalizers and nonrecanalizers made better mRS cutpoints less informative.

Conclusions:
Thrombectomy trials tend to enroll homogenously severe patients in whom reperfusion benefits cluster, especially at the mRS 4 to 3 transition; so sliding dichotomies based on single variables do not substantially increase trial power. Further analysis will examine if combinations of prognostic variables confers additional sliding dichotomy power.
Abstract WP153: Establishing Kinimatic Age-referenced Normative Values of the Upper Extremity Using the InMotion 2 Robot
Authors: Creelman Carly A , Kim Grace J , Taub Michael , O'Dell Michael W
Published: July 2021

Introduction:
The use of technology in stroke rehabilitation is growing rapidly. Upper extremity robotic devices provide both therapeutic intervention as well as objective kinematic assessment to evaluate arm ability of individuals with stroke. The InMotion 2® is a shoulder/elbow robot widely used in the clinic and within stroke rehabilitation research. It has the capability to provide kinematic assessment of the arm, however there are no age-referenced normative values available for comparison to a healthy population. The aim of this study was to establish normative kinematic values for the InMotion 2 robot.

Hypothesis:
Not Applicable.

Methods:
Forty healthy individuals with no history of stroke or other neurological conditions with full passive and active range of motion in both upper extremities were recruited from the community. Subjects were recruited based on age (40-49, 50-59, 60-69, 70-80), 10 subjects per group (5 males and 5 females). Subjects were assessed on circle and clock drawing tasks with their dominant and non-dominant arm over three trials. The kinematic parameters measured included smoothness, joint independence, hold deviation, and displacement. The mean (M) and standard deviation (SD) of dominant hand test 1 and 2 were averaged together for combined scores across age groups.

Results:
The following age referenced normative values were determined for each kinematic parameter: smoothness (m/s), mean and SD for 40-49 age group (.585; .027), 50-59 (.566; .033), 60-69 (.540; .048), and 70-80 (.561; .033); joint independence: 40-49 (.861; .019), 50-59 (.858; .0394), 60-69 (.839; .030), and 70-80 (.853; 024); hold deviation (meters), 40-49 (.017; .005), 50-59 (.019; .004), 60-69 (.019; .006), and 70-80 (.022; .004); displacement (meters), 40-49 (.132; .001), 50-59 (.132; .001), 60-69 (.132; .001), and 70-80 (.131; .0004).

Conclusion:
The analysis demonstrated that age, sex, and hand dominance did not have a significant effect on normative kinematic outcomes, however age referenced normative values establish baseline and ceiling levels which provide more meaning when interpreting scores for individuals with stroke. Further research investigating the reliability of the kinematic parameters is currently underway.
Abstract WP165: Silent Brain Infarction and Risk of Future Stroke: A Systematic Review and Meta-Analysis
Authors: Gupta Ajay , Giambrone Ashley , Gialdini Gino , Finn Caitlin B , Delgado Diana , Gutierrez Jose , Wright Clinton , Beiser Alexa B , Seshadri Sudha , Pandya Ankur , Kamel Hooman
Published: July 2021

Introduction:
Silent brain infarction (SBI) on magnetic resonance imaging (MRI) is relatively frequently detected but of uncertain clinical significance.

Hypothesis:
We hypothesized that a pooled estimate from all relevant published and unpublished sources will demonstrate SBI to be an independent risk factor for future stroke.

Methods:
We performed a systematic review and meta-analysis to summarize the association between MRI-defined SBI and future stroke. We searched for relevant literature in Ovid MEDLINE, Ovid Embase, and the Cochrane Library Database from inception to April 3, 2015. All cohort studies involving adults with MRI detection of SBI who were subsequently followed for incident clinically-defined stroke were eligible. Study data and quality assessment was recorded in duplicate with disagreements in data extraction resolved by a third reader.

Results:
We studied 14,764 subjects from 13 studies with a mean follow-up ranging from 25.7 to 174 months. SBI predicted the occurrence of stroke with a random effects crude relative risk of 2.94 (95% CI 2.24-3.86, P<0.0001; Q=39.649, P<0.0001, Figure Panel A). In the 8 studies of 10,427 subjects providing cardiovascular risk factor-adjusted hazard ratios (HR), SBI was an independent predictor of incident stroke (HR of 2.08 [95% CI 1.69-2.56, P<0.0001, Figure Panel B]; Q=8.99, P=0.253). In a subgroup analysis pooling 9,483 stroke-free individuals from large population-based studies, SBI was present in ∼18% of participants and remained a strong predictor of future stroke (HR 2.06 [95% CI 1.64-2.59], p<0.01). A potential limitation of the existing literature was that MRI techniques for detecting SBI were variable across studies and were detected using older generation MRI equipment.

Conclusion:
SBI is present in approximately 1 in 5 stroke-free older adults and is associated with 2-fold increased risk of future stroke.
Abstract WP177: Bacterial Endocarditis and Acute Stroke: a Population-based Study
Authors: Flaherty Matthew L , Kleindorfer Dawn O , Khoury Jane C , Alwell Kathleen , Moomaw Charles J , Woo Daniel , Adeoye Opeolu , Ferioli Simona , Mackey Jason , Khatri Pooja , Martini Sharyl , De Los Rios La Rosa Felipe , Kissela Brett M
Published: July 2021

Background:
Bacterial endocarditis is a rare but important cause of stroke, as treatment strategies and prognosis differ compared with other stroke mechanisms. We sought to determine the incidence of stroke associated with endocarditis and the clinical characteristics and course of affected patients.

Methods:
This study was carried out as part of a population-based epidemiologic study of all stroke subtypes conducted every five years in the Greater Cincinnati/Northern Kentucky region. All residents of our five-county region admitted to local hospitals with ischemic or hemorrhagic stroke in 2005 and 2010 were identified via ICD-9 codes 430-436 from hospital and emergency room discharge lists. Patients with an active diagnosis of endocarditis at the time of stroke or a new diagnosis during their acute hospitalization for stroke were identified by study nurse and physician review of clinical data. The incidence of stroke associated with endocarditis was calculated and age-, sex-, and race-adjusted to the 2000 US population.

Results:
Presumed bacterial endocarditis was associated with 26 of 5311 strokes (0.5%). The incidence of stroke associated with endocarditis was 1.2 (95% CI 0.7-1.7) cases per 100,000 persons per year. Two strokes were perioperative at the time of valve repair. A majority of cases (24/26) were primary ischemic stroke; symptomatic hemorrhagic conversion occurred in 3 of the 24 ischemic cases. Only 7 of 26 patients had a known diagnosis of endocarditis at the time of stroke. A minority of patients had fever (8/26) or systolic blood pressure <120 (7/26) at first medical encounter, while a majority (15/26) had leukocytosis. Compared with stroke patients without endocarditis, those with endocarditis were younger (58 vs. 72, p < .001), more likely to be black (42% vs. 22%, p = .02), and more likely to die (30-day all-cause case-fatality 31% vs 16%, p =.06). No endocarditis patients were treated with IV tPA.

Conclusions:
Endocarditis is an uncommon cause of stroke associated with a high case-fatality. Patients presenting with acute stroke due to endocarditis often lack classic signs of infection such as fever or hypotension.
Abstract WP178: Acute Stroke Ischemic Symptom Onset-to-Arrival Time in Michigan Hospitals
Authors: Farooq Muhammad U , Thomas Kathie
Published: July 2021

Objectives:
Stroke is the fifth-leading cause of death and the leading cause of disability in the United States. One of the primary goals of the American Heart Association/American Stroke Association is to increase the number of acute stroke patients arriving at emergency departments (EDs) within 1-hour of symptom onset. Earlier treatment with thrombolysis in patients with acute ischemic stroke translates into improved patient outcomes. The objective of this abstract is to examine the association between the use of emergency medical services (EMS) and symptom onset-to-arrival time in patients with ischemic stroke.

Methods:
A retrospective review of ischemic stroke patients (n = 8873) from 25 Michigan hospitals from January 2012-December 2014 using Get With the Guidelines databases was conducted. Symptom onset-to-ED arrival time and arrival mode were examined.

Results:
It was found that 17.4% of ischemic stroke patients arrived at the hospitals within 1-hour of symptom onset. EMS transported 69.1% of patients who arrived within 1-hour of symptom onset. During this 1-hour period African American patients (22%) were less likely to use EMS transportation as compared to White patients (72%). The majority of patients, 41.8%, arrived after 6-hours of symptom onset. EMS transported only 40% of patients who arrived after 6-hours of symptom onset. As before, during this 6-hour period African American patients (20%) were also less likely to use EMS transportation as compared to White patients (75%). Symptom onset-to-ED arrival time was shorter for those patients who used EMS. The median pre-hospital delay time was 2.6 hours for those who used EMS versus 6.2 hours for those who did not use EMS.

Conclusions:
The use of EMS is associated with a decreased pre-hospital delay, early treatment with thrombolysis and improved patient outcomes in ischemic stroke patients. Community interventions should focus on creating awareness especially in minority populations about stroke as a neurological emergency and encourage EMS use amongst stroke patients.
Abstract WP192: The Association Between Carotid Artery Atherosclerosis and Silent Brain Infarction: a Systematic Review and Meta-analysis
Authors: Finn Cailtin , Giambrone Ashley , Gialdini Gino , Delgado Diana , Baradaran Hediyeh , Kamel Hooman , Gupta Ajay
Published: July 2021

Introduction:
Silent brain infarctions (SBI) are asymptomatic lesions whose presence is associated with a two-fold increased risk of future stroke. Though carotid atherosclerosis is responsible for ∼20% of ischemic strokes, the strength of association between carotid disease and SBI is unclear based on estimates from individual studies.

Hypothesis:
We hypothesized that a synthesis of the existing literature would show that two separate manifestations of carotid atherosclerosis, carotid intima-media thickening (IMT) and luminal stenosis, are associated with SBI.

Methods:
We searched multiple online literature databases from their inception to April 2015. Articles were included if they reported an association between MRI defined SBI and carotid IMT or stenosis, excluding SBI evaluation after a procedure. The association between SBI and IMT or stenosis was estimated using pooled random-effects (RE) standard mean difference (SMD) or odds ratio, respectively.

Results:
We pooled 6 IMT studies reporting on 1434 subjects with SBI and 5058 subjects without SBI. Subjects with SBI had a larger mean IMT compared to subjects without SBI (pooled RE SMD, 0.36; 95% CI, 0.21 to 0.51; P<0.0001, Figure Panel A). We pooled 9 carotid stenosis studies reporting on 11,177 subjects (1839 subjects with and 9338 subjects without carotid stenosis). In total, 141 (22.5%) of the subjects with carotid stenosis had SBI, while 1568 (16.8%) of the subjects without carotid stenosis had SBI. Our pooled RE analysis showed a significant positive relationship between carotid stenosis and SBI (OR, 2.62; 95% CI, 2.04 to 3.36; P<0.0001, Figure Panel B).

Conclusions:
Both carotid IMT and stenosis are significantly associated with the presence of SBI. Patients with SBI and carotid atherosclerosis may represent a group at higher risk of clinically overt stroke and who may therefore benefit from more intensive stroke prevention measures.
Abstract WP214: Transcranial Color Coded Sonography versus Transcranial Doppler for the Detection of Right-to-left Shunt and Patent Foramen Ovale in Young Patients With Stroke
Authors: Libardi Milena C , Camilo Millene R , Fabio Soraia R , Martins Filho Rui Kleber V , Rocha Letícia J , Santos Renata S , Barreira Clara M , Cougo-Pinto Pedro T , Alessio-Alves Frederico F , Dias Francisco A , Abud Daniel G , Pontes-Neto Octávio M
Published: July 2021

Introduction:
Patent Foramen Ovale (PFO) is the most common right-to-left shunt (RLS) and is often found in young patients with stroke related to paradoxical embolism. Contrast-Enhanced Transesophageal Echocardiography (TEE) is considered a gold standard to visualize PFO. Transcranial Doppler (TCD) with bubble test is often used to detect RLS with good correlation to TEE for the diagnostic of PFO. More recently, Transcranial Color Coded Sonography (TCCS) which included B-mode and color coded imaging has overcome TCD in many clinical applications but the accuracy of TCCS for detection of RLS and PFO has not been systematically evaluated.

Hypothesis:
To determine if the TCCS is an accurate tool to identify both PFO and RLS.

Methods:
We investigate 106 patients with ischemic stroke under 55 years-old admitted from 2012 to 2014 in a tertiary academic hospital. Patients were evaluated with TEE, TCD and TCCS, and all exams included a saline bubble test. The examiners were blinded for the other tests results. Kappa agreement was calculated inter-examiners for TCCS and TCD. Accuracy of TCCS was calculated in comparison to TEE.

Results:
We detected a RLS in 54 (50.9%) patients (age mean 43.9 ± 8.2) with kappa agreement 0.92 (95%CI 0.78-1.0) when performed TCCS and TCD. TEE and TCSS were positive in 23/98 (23.4%) and TEE did not reveal contrast in 20/98 (20.4%). In 30 (28.3%) patients only TEE revealed a PFO. TCSS had a sensitivity of 88.4% (95%CI 0.68-0.97), specificity of 72.2% (95%CI 0.60-0.81) and positive likelihood ratio of 3.18 (2.14-4.73) of the diagnosis of PFO.

Conclusion:
TCCS and TCD had an excellent agreement. TCCS has a good accuracy for the detection of PFO and RLS in young patients with stroke.
Abstract WP224: Transverse Sinus Hypoplasia as a Predisposing Factor for Cerebral Venous Thrombosis
Authors: Chavarria-Medina Monica , Barboza Miguel , Varela Elizabeth , Patriño-Rdoriguez Hernán M , Becerril Mayra , Arauz Antonio
Published: July 2021

Background:
Transverse sinuses (TS) are frequently asymmetric. Hypoplasia or aplasia of TS is a common anatomical variation, right TS is dominant in 61% of cases. The relationship between hypoplastic TS and cerebral venous thrombosis is not well established.

Hypothesis:
Transverse sinus hypoplasia is a predisposing factor for ipsilateral transverse sinus thrombosis

Methods:
We retrospectively evaluated 27 confirmed cases with isolated transverse sinus thrombosis and 54 age-and-sex matched controls, treated in a Neurological tertiary center from 2010 to 2015. A stroke neurologist and a neuroradiologist measured TS using an MRI sequence (Inhance 3D Inflow IR); interrater reliability was calculated using Bland-Altman plots. Hypoplasia was defined as a transverse sinus diameter less than 50% of the cross-sectional diameter of the lumen of the distal superior sagittal sinus. Univariate analysis was performed to evaluate the association between transverse sinus hypoplasia (TSh) and thrombosis.

Results:
There was a good inter-rater reliability (p=0.55 on the Bland-Altman plot by ANOVA test). There were a total of 45 left hypoplastic transverse sinuses (TS) (19 [70.4%] cases vs. 26 [48.1%] controls), and 16 right hypoplastic TS (11 [40.7%] cases vs. 5 [9.3%] controls). Ipsilateral thrombosis was present in 9 (33.3%) right and 15 (55.5%) left hypoplastic transverse sinuses. Transverse sinus thrombosis was more likely to be present when associated with left TSh (RR 2.57, 95% CI 1.17-5.69; p=0.001), than right TSh and ipsilateral thrombosis (RR 0.15, 95% CI 0.04-0.57; p<0.001).

Conclusion:
Isolated transverse sinus hypoplasia might be a predisposing factor for ipsilateral transverse sinus thrombosis.
Abstract WP259: Metabolomic Analysis of Ischemic Brain Tissue to Explore Specific Metabolic Pathway Assosiated With Cerebral Ischemia
Authors: Yamamoto Yusuke , Hosoda Kohkichi , Irino Yasuhiro , Tanaka Jun , Imahori Taichiro , Nakai Tomoaki , Kohmura Eiji
Published: July 2021

Objectives:
We investigated metabolic profiles of brain tissue in middle cerebral artery occlusion (MCAO) model of rats to explore the specific changes associated with acute ischemia.

Methods:
Focal cerebral ischemia was induced in rats using filament occlusion of the MCA. Tissue samples from the ischemic lesion were collected before and after ischemia(0, 30, 60, 120min, n=7-10). Sham operated rats were treated in the same way except MCAO (n=10). Water-soluble metabolites were extracted and analyzed using gas-chromatography/mass-spectrometry(GS/MS). The obtained data were analyzed by multivariate statistics to explore metabolic pathways associated with ischemia. The associated metabolic enzymes were investigated with RT-PCR and Western blot.

Results:
About ninety metabolites were identified by GC/MS. Principal component analysis and heatmap demonstrated clear separation between ischemia and control group (Figures). The most significant changes were decrease of fructose-6-phosphate and ribulose-5-phosphate, increase of hydroxybutyrate, and increase of GABA with time. These results suggested acceleration of pentose phosphate pathway to increase NADPH, upregulation of keton metabolism and neuroprotection by GABA. RT-PCR and Western blot did not indicate significant changes of transcription and protein level of the enzymes involved in these pathways and suggested changes of the enzyme activity by modification after transcription or translation such as phosphorylation.

Conclusions:
These results suggested the presence of neuroprotective metabolic change in the ischemic brain.
Abstract WP262: White Matter Stroke and Alzheimer’s Pathology Synergize to Worsen Outcomes in the First Clinically Relevant Mouse Model of Mixed Vascular and Alzheimer’s Disease Dementia
Authors: Huang Julia , Nunez Stefanie , Cole Gregory , Teng Edmond , Hinman Jason D
Published: July 2021

Introduction:
Microvascular stroke and Alzheimer’s disease (AD) account for the majority of dementia diagnoses with 50% of patients having mixed dementia with features of both microvascular stroke in white matter and AD pathology. Clinico-pathologic studies indicate that white matter hyperintensities present on magnetic resonance imaging correlate with the degree of AD pathology in patients supporting pathologic overlap. This significant co-morbidity indicates an interactive neurobiologic relationship yet it is unclear if these two pathologies synergize or simply co-exist. Prior studies to model stroke and AD pathology have struggled to identify clinically relevant paradigms and time courses that could reasonably link the two disorders.

Hypothesis:
Subcortical white matter stroke synergizes with AD to worsen outcomes.

Methods:
We have established a clinically relevant model of mixed dementia by introducing subcortical white matter stroke into EFAD transgenic mice that harbor 5 common AD-associated mutations and knock-in human ApoE alleles under control of the murine ApoE promoter. Strokes were introduced either before or after significant amyloid plaque accumulation and the additive effect of stroke determined.

Results:
In E4FAD mice (with ApoE4 allele) that have already developed amyloid pathology (>6 months of age), white matter strokes are 70% larger in size (p=0.06) but not associated with worsening gliosis or impaired survival of oligodendrocytes in the peri-infarct region. The molecular organization of axons adjacent to stroke is markedly worse in mice with AD pathology. In younger E4FAD mice, the introduction of a white matter stroke prior to the significant accumulation of amyloid pathology results in worsening plaque burden both globally and in overlying cortex.

Conclusions:
These data suggest that AD and white matter stroke synergize to worsen both the outcome of stroke occurring in the setting of AD. Similarly early stroke synergizes with amyloid generation to accelerate plaque deposition. This clinically relevant model of mixed dementia will be useful in both preclinical drug disease for both AD and stroke therapies as well as crucial to the discovery of neurobiologic pathways that combine to promote stroke and AD pathologies.
Abstract WP266: Deficiency of Angiotensin Converting Enzyme 2 Causes Deterioration of Cognitive Function
Authors: Iwanami Jun , Mogi Masaki , Wang Xiao-Li , Tsukuda Kana , Higaki Akinori , Kukida Masanori , Nakaoka Hirotomo , Yamauchi Toshifumi , Bai Hui-Yu , Shan Bao-Shuai , Min Li-Juan , Horiuchi Masatsugu
Published: July 2021

Introduction:
The classical renin-angiotensin system (RAS), known as the angiotensin (Ang) converting enzyme (ACE)/Ang II/Ang II type 1 (AT1) receptor axis, induces various organ damage including cognitive decline. On the other hand, the ACE2/Ang-(1-7)/Mas receptor axis has been highlighted as exerting antagonistic actions against the classical RAS axis in the cardiovascular system. However, the roles of the ACE2/Ang-(1-7)/Mas axis in cognitive function largely remain to be elucidated, and we therefore examined possible roles of ACE2 in cognitive function.

Methods:
Male 10-week-old C57BL6 (wild-type: WT) mice and ACE2 knockout (KO) mice were subjected to the Morris water maze task to evaluate spatial cognitive function. Vascular dementia model were induced by bilateral common carotid artery stenosis (BCAS). The Morris water maze task was performed 6 weeks after BCAS operation.

Results:
ACE2KO mice exhibited significant impairment of spatial cognitive function, compared with that in WT mice, without significant difference in cerebral blood flow determined by laser speckle flowmetry and morphological changes in the hippocampus between both strains. Superoxide anion production in the hippocampus tended to be increased in ACE2KO mice, with increased mRNA levels of NADPH oxidase subunit in the hippocampus of ACE2KO compared with WT mice. Protein level of superoxide dismutase (SOD) 3 tended to be decreased in ACE2KO mice compared with WT mice. AT1 receptor mRNA level in the hippocampus was higher in ACE2KO mice compared with WT mice. In contrast, AT2 receptor mRNA level in the hippocampus did not differ between the two strains. Mas receptor mRNA was highly expressed in the hippocampus compared with the cortex, with no significant difference between ACE2KO and WT mice. Brain-derived neurotrophic factor (BDNF) mRNA was lower in the hippocampus in ACE2KO mice compared with WT mice. Escape latency after BCAS was prolonged in WT mice compared with sham operated mice, whereas impaired cognitive function in ACE2 KO mice was not further exaggerated after BCAS.

Conclusion:
Taken together ACE2 deficiency resulted in impaired cognitive function probably due to enhanced oxidative stress and a decrease in BDNF.
Abstract WP275: Hemorrhagic Transformation in Large Cerebral Infarction of Rats Pretreated With Dabigatran or Warfarin
Authors: An Sunho , Kwon Il , Kim Jayoung , Yoo Joonsang , Lee Kijeong , Baek Jang-Hyun , Kim Young Dae , Yang Seung-Hee , Choi Hyun-Jung , Nam Hyo Suk , Heo Ji Hoe
Published: July 2021

Introduction:
Dabigatran is effective in preventing stroke and reduces the risk of intracerebral hemorrhage when comparing with warfarin in patients with atrial fibrillation. However, it is uncertain whether hemorrhagic transformation (HT) after large cerebral infarction is also less frequent in dabigatran users than warfarin users.

Hypothesis:
We hypothesized that intracerebral HT would occur less frequently following large cerebral infarction in rats pretreated with dabigatran than those with warfarin. We also compared the change of matrix metalloproteinases (MMPs), which play a key role in HT.

Methods:
We performed randomized, double-blind experiments comparing warfarin and dabigatran in rats. After treatment with warfarin (0.2 mg/kg), dabigatran (20 mg/kg), or normal saline for 7 days, male wistar rats were subjected to permanent middle cerebral artery occlusion (MCAO) using a nylon thread. After 22 hours of MCAO, magnetic resonance imaging (MRI) was undergone (9.4T MR scanner, slice thickness = 0.5 mm). Operative procedures and assessment of MRI findings were performed by investigators who were blind to the group information. The presence of HT was assessed on gradient recalled-echo and infarction volume was measured on diffusion-weighted image. The MMP-2 and MMP-9 activities in brain tissues (obtained 24 hours after MCAO) were investigated using gelatin zymography.

Results and Conclusions:
Of the 33 rats with MRI, HT was observed less frequently in the dabigatran group than the warfarin group (placebo 14% [2/14], dabigatran 0% [0/10], and warfarin 100% [9/9], p < 0.001 [dabigatran vs warfarin]). The volume of infarction was similar between the groups (placebo 432.45 ± 78.35 mm3, dabigatran 432.42 ± 60.27 mm3, and warfarin 446.55 ± 73.55 mm3). MMP-2 and MMP-9 activities were not different between the groups. In the placebo, dabigatran, and warfarin groups, mean international normalized ratio were 1.38 ± 0.13, 1.73 ± 0.20, and 4.72 ± 2.92, respectively; mean activated partial thromboplastin times were 30.20 ± 7.49, 31.14 ± 7.02, and 55.06 ± 24.05, respectively. The risk of HT after large cerebral infarction was remarkably reduced in rats pretreated with dabigatran. MMPs did not seem to play a major role in reduced risk of HT.
Abstract WP3: EMS Routing for Endovascular Patients- One Health Care Systems Successful Model
Authors: Martin Coleman O , Hawkins Angela M , Olds Karin , Akhtar Naveed , Holloway William , King Shelleen , McClintick Jay
Published: July 2021

Background:
Annually, over 1500 stroke patients are seen within a large metropolitan health system. The health system encompasses a designated comprehensive (CSC) and multiple primary (PSC) stroke hospitals with varying capabilities to manage stroke patients, resulting in varied care delivery. While CSCs mitigate inconsistencies by establishing a standard of stroke care, one shortcoming of the CSC model is lack of regulation in transfer of patients between centers within a health system containing multiple stroke designations.

Purpose:
The purpose of the project was to create a streamlined, emergency stroke work-up process across the various levels of stroke hospitals and to apply rapid routing practices for EMS when transferring stroke patients between facilities. These changes could reduce treatment times and optimize resources to facilitate transportation of stroke patients to the appropriate center.

Methods:
The system stroke steering team, in collaboration with regional EMS directors initiated 5 primary processes to reduce delays. These included 1) door in to door out times of 60 minutes, 2) loading radiology images into a cloud environment, 3) development of EMS algorithms, 4) prompt follow-up reports on stroke transfers, and 5) rapid loop-closure on gaps in the process. A reduction in door-to-therapy time and measures of patient outcome were used as indicators for effectiveness.

Results:
Implementation of a streamlined ED process and new routing protocol was associated with improved door-to-door times, door-to-treatment times and EMS transport times. Additionally, risk-adjusted mortality decreased from 0.7 in 2012 to 0.3 in 2014. Similarly, thrombolytic complications in intravenous and endovascular patients decreased from 7.5% in 2012 to 1.7% in 2014, while treatment rates in both increased.

Conclusion:
Within a large health system, utilizing a consistent ED process and new EMS routing protocol could contribute to improved outcomes. This raises the possibility that implementing system routing practices may improve collaboration within stroke systems of care and advance the CSC model.
Abstract WP30: Incorporation of Automated CT Perfusion-based Core Volume Measurement in a Prognostic Tool for Anterior Large Vessel Occlusions: Pittsburgh Response to Endovascular Score-2 (PRE-2)
Authors: Rangaraju Srikant , Haussen Diogo , Rebello Leticia C , Frankel Michael , Jovin Tudor , Nogueira Raul
Published: July 2021

Background:
Endovascular therapy (ET) benefits patients with proximal anterior large vessel occlusions (LVO) provided ischemic core volume (CV) is not large. CT ASPECTS is a surrogate of CV and along with age and NIHSS, strongly predicts 3-month clinical outcomes and features in prognostic scores (PRE, HIAT-2). CV measured by CT perfusion (CTP) may overcome the low inter-rater reliability and subjectivity of ASPECTS.

Objective:
To determine whether the prognostic accuracy of the PRE score for good outcome (3-month mRS 0-2) is improved if CT ASPECTS is replaced by CV (cerebral blood flow <30%) measured by Rapid processing of Perfusion and Diffusion (RAPID) software.

Methods:
Consecutive patients (Oct 2010-Feb 2015) with carotid terminus, M1 and M2 MCA occlusions who had CTP with RAPID processing prior to ET were included. A multivariable model with age, NIHSS and CT ASPECTS as covariates was compared to a model containing age, NIHSS and CV measured by RAPID to predict good outcome. After weighting each variable by regression coefficients, a revised score with RAPID CV instead of CT ASPECTS (PRE-2) was derived. AUCs of the PRE and PRE-2 scores for good outcome were compared.

Results:
188 patients were included (mean age 62.5±15 years, median NIHSS 18 [IQR 13-21], median ASPECTS 8 [IQR 7-9]). TICI2B/3 reperfusion was achieved in 82.4% and good outcome in 59.3% of patients. Age, NIHSS and ASPECTS independently predicted good outcome (p<0.001). After replacing CT ASPECTS with CV, age, NIHSS and CV were found to independently predict good outcome (p<0.05). Predicted probabilities for good outcome in both models were strongly correlated. The PRE-2 score had similar predictive power for good outcome (AUC=0.79) as compared to the original PRE score (AUC=0.81). PRE-2≥130 predicted 0% (0/18) chance of good outcome.

Conclusions:
CV measured by RAPID can substitute CT ASPECTS in the PRE score without any change in predictive accuracy. Validation of the PRE-2 score is warranted.
Abstract WP313: Quality of Ischemic Stroke-related Care in Patients With Chronic Kidney Disease (CKD) on Dialysis: Findings From Get With the Guidelines-stroke
Authors: El Husseini Nada , Fonarow Gregg C , Smith Eric E , Ju Christine , Schwamm Lee H , Hernandez Adrian F , Schulte Phillip , Xian Ying , Goldstein Larry B
Published: July 2021

Objectives:
To assess the quality of ischemic stroke-related care based on American Heart Association (AHA) Get With The Guidelines (GWTG)-Stroke metrics for patients receiving dialysis compared to those with less severe or no CKD .

Methods:
The analysis is based on data from 232,236 Medicare-eligible fee-for-service patients admitted to 1581 GWTG-Stroke participating hospitals between January 2009 and December 2012. GFR was determined based on the MDRD study equation. Patients receiving dialysis were identified by ICD-9 diagnosis codes (V45.11 renal dialysis status, 585.6 end stage renal disease, V56.X encounter for dialysis and dialysis catheter care).

Results:
Compared to no CKD, dialysis patients received fewer guideline-based therapies (Table). Compared to other CKD stages, dialysis patients less often received VTE prophylaxis, timely treatment with IV-tPA, and defect free care. Treatment with early antithrombotics, discharge on antithrombotics, anticoagulation for atrial fibrillation, and statin use were lowest in patients with CKD stage 5.

Conclusion:
Among Medicare beneficiaries with acute ischemic stroke, guideline-adherent care is less frequent in patients on dialysis compared to those with less severe or no CKD. Additional work is needed to determine the reasons for these differences.
Abstract WP342: Antithrombotics Within 24 Hours After Recanalization Treatment: Is it Safe?
Authors: Kim Beom Joon , Jeong Han-Gil , Yang Mi-Hwa , Han Moon-Ku , Park Seong-Ho , Bae Hee-Joon
Published: July 2021

Background:
Majority of hemorrhagic transformation (HTf) occurs within 24 hours after IV or IA treatment, and earlier antithrombotics may be useful in preventing early reocclusions or ischemic neurologic deteriorations. However, the safety of early antithrombotics ≤24-hour after recanalization treatment is not sufficiently evaluated.

Methods:
From a total of 6777 stroke cases who admitted to Seoul National University Bundang Hospital between July 2007 and March 2015, the authors collected eligible cases with the following inclusion criteria; (1) Lesion-documented ischemic strokes (N=5451); (2) received recanalization treatments (N=792). We excluded 72 cases with (1) missing in the time information (N=19), (2) ultraearly bleeding complications (N=41), (3) extremely grave prognosis (N=5), and (4) surgical treatment (N=7). We systemically gathered the exact timing of antithrombotics use from a database of electronic bar-code medication administration system.

Results:
Of the 720 analyzable cases, male was 57% (n=407), mean age was 68.9 ± 12.8, and median NIHSS score was 12 [7 - 19] point. Recanalization treatment was consisted of 34% (n=243) of IV-only, 32% (=231) of IA-only, and 34% (n=246) of combined IV-IA strategies. Outcomes after stroke was as following; 218 (30%) any HTf, 31 (4%) symptomatic HTf, and 266 (37%) mRS score 0 - 1 at 3 months. In this population, antithrombotics were initiated within 24 hours after recanalization treatment in 64% (n=458) of cases and within 12 hours in 24% (n=170) of patients. Multivariable analyses revealed that early initiation of antithrombotics within 24 hours after recanalization treatment was significantly associated with lower odds of having any HTf (adjusted OR, 0.69; 95% CI, 0.48 - 0.98). Early initiation was not significantly associated with symptomatic HTf (0.71; 0.34 - 1.46) and mRS score 0 - 1 at 3 months after stroke (1.41; 0.97 - 2.06).

Conclusions:
Earlier initiation of antithrombotics within 24 hours after recanalization treatment may not increase hemorrhagic complications after stroke. Further clinical research is warranted to clarify which subgroup of stroke patients will benefit of earlier antithrombotics.
Abstract WP376: Using the Plan-Do-Study-Act Model to Improve IV TPA Administration Times
Authors: Page Ashley , Motz Deb , Hansen Sara , Cline Beth , Patterson Michele , Moore Tracy , Huey Dicky , Austin Tommye
Published: July 2021

Background:
Current guidelines for management of acute ischemic stroke include distinct recommendations regarding IV Tissue Plasminogen Activator (TPA) administration times. While 75% of all strokes are ischemic, over 70% of patients are treated after the 3 hour window, placing them at an increased risk for stroke complications. From FY 2014 to FY 2015, Baptist Health System Emergency Departments (ED) had proven that the implementation of the Plan-Do-Study-Act (PDSA) Performance Improvement Model can significantly improve IV TPA Administration Times.

Purpose:
The purpose of this poster is to describe the use of the Plan-Do-Study-Act Model in improving IV TPA Administration times within Baptist Health System Emergency Departments.

Methods:
Emergency Departments (Physician Champions, Directors, and Nursing staff) collaborated to standardize processes using lean methodology. Actions taken to improve IV TPA administration times through use of the PDSA include analyzing all TPA fallouts, reporting monthly findings at the regional ED service line (nursing), and submitting findings to the Stroke Coordinator, CNO, and ED Physician Quality Director for follow-up. In addition to the previously used processes of stroke alert notification and evaluating the patient at the door, TPA administration would no longer be held if there was a delay in the telemedicine response. If the ED Physician determined that the patient was a candidate for TPA therapy, the order would be given to administer TPA and the ED Physician would be able to cancel the telemedicine consult if the TPA was administered before reaching the neurologist. The ED Physician would then document the delay in treatment, as appropriate.

Results:
BHS received the Target Stroke Honor Roll and significantly improved Door to IV TPA therapy within 60 minutes from 53.8% (57/106) in 2013 to 70.5% (62/88) in 2015.

Conclusion:
In conclusion, BHS showed significant improvement in TPA Administration times through the use of the PDSA Method. Administrative, Physician, Stroke Leadership, and Nursing collaboration with performance improvement items were instrumental in reducing IV TPA administration times in Emergency Departments.
Abstract WP412: Neurovascular Imaging is not Always Normal in Neonatal Arterial Ischemic Stroke
Authors: Askalan Rand , Siddiq Ishita , Armstrong Derek , deVeber Gabrielle , MacGregor Daune , Moharir Mahendranath
Published: July 2021

Background:
Neonatal arterial ischemic stroke (AIS) is the most common pediatric stroke occurring in more than 1/4000 live births with a risk of recurrence of less than 1%. The presence of an arteriopathy is associated with high risk of recurrence in childhood stroke. However, The prevalence and risk factors of an arteriopathy in neonatal stroke are not known.

Objective:
We sought to characterize the subgroup of neonates with AIS who have abnormal vasculature.

Patients and Methods:
This is a single center retrospective case-control study of patients with neonatal stroke from 1991-2012. Charts were reviewed for neonates with AIS and neuroimaging that included vascular imaging (MRI/MRA). Clinical data of patients with abnormal MRA was compared to the control group of neonates with AIS but a normal MRA.

Results:
A total of 142 cases of neonatal AIS were identified of which 82 patients had MRI/MRA. Among the neonates with vascular neuroimaging, 30 had abnormal vessels (minimum prevalence rate of 36%). The majority of vascular abnormalities were stenotic or hypoplastic branches. Two patients (7%) had dissection. Young maternal age, positive maternal GBS, C-section delivery, low APGAR scores, low Hgb, and cardiac defects were significantly (p < 0.05) more common in neonates with abnormal vessels.

Conclusion:
Neurovascular imaging is challenging in neonates so often not performed. However, we recommend that an MRA to be performed in neonates with AIS who have any of the risk factors identified in this study. Early diagnosis of their vasculopathy may change their stroke management and impact outcome.
Abstract WP418: Outcome Comparison Between Patients Suffering a Stroke/TIA or a Moderate/major Bleed: Data From the ‘Triple Antiplatelets for Reducing Dependency After Ischaemic Stroke’ (TARDIS) Trial
Authors: Woodhouse Lisa , Sprigg Nikola , Bath Philip M
Published: July 2021

Introduction:
After ischaemic stroke (IS) or TIA, recurrence and moderate/major bleeding are each associated with worse outcome. We compared baseline characteristics and outcomes for patients who did and did not have recurrence or bleeding using data from the ongoing TARDIS trial.

Method:
TARDIS is assessing the safety and efficacy of intensive vs guideline antiplatelet agents in 4,100 patients with acute non-cardioembolic IS or TIA. Information on bleeding, and recurrent IS and TIA is collected up to day 90. Functional outcome are assessed centrally with blinding to treatment assignment at day 90. Data are unadjusted odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI), and do not take account of treatment assignment.

Results:
In 2697 recruited patients (of a planned 4100), recurrent events (178, 6.6%) were more common in patients with a qualifying event of TIA (p=0.017). Major (51 patients, 1.9%), including fatal (7 patients, 0.3%) bleeding were uncommon. Patients with a recurrence or moderate/major bleeding event had worse outcomes at day 90 than those without such events: more deaths, dependency (modified Rankin Scale), disability (Barthel Index), cognitive impairment (TICS-M), worse quality of life (EQ-5D HUS) and more mood disturbance (Zung depression scale) - all comparisons p<0.001.

Conclusion:
Recurrent events are more common after TIA. Both recurrence and bleeding are associated with a worse outcome.