bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP54: High Serum Troponin Levels and Sex Differences With First Time Ischemic Stroke: Findings From the Chronic Renal Insufficiency Cohort Study
Authors: Liu Zuolu , Ng Kwan L
Published: October 2018

Introduction and Hypothesis:
High troponin levels reflect myocardial damage in patients with heart disease and predict poor prognosis in stroke and cardiomyopathies. In the study, we test the hypothesis that high troponin levels in the setting of chronic renal insufficiency (CRI) significantly predict the risk of first time stroke.

Method:
The Chronic Renal Insufficiency Cohort Study enrolled a total of 3,477 patients with no previous history of stroke at baseline were used in this study. High troponin level is defined as troponin levels ≥0.03 ug/L. Incident hemorrhagic and ischemic strokes were classified using ICD-9. The associations between baseline troponin levels and incidence of hemorrhagic and ischemic stroke and risk of all-cause mortality were analyzed prospectively using multivariate Cox’s regression analysis technique.

Results:
With an average (SD) of 7.7 (1.5) years of follow-up, 23 participants developed incident hemorrhagic stroke (HS), and 84 developed incident ischemic stroke (IS). Participants with high troponin had significantly higher IS rate than those with low troponin (9.69% vs. 2.81%, p<.0001). After adjustment for age, race, smoking, body mass index, systolic blood pressure, eGFR, total cholesterol to HDL ratio, diabetes, and myocardial infarction, Cox’s models indicate that participants with high troponin had 2.68 times higher risk of incident IS than those with low troponin (HR: 2.68, 95%CI: 1.55-4.62, p=0.0004). Females with high troponin had a significantly higher risk of IS than males (excess HR=3.41, 95%CI 1.25-8.41, p=0.016). Participants with high troponin had a significantly increased risk of all-cause mortality in both sexes. Of them, females with high troponin had a significantly higher risk of all-cause mortality than males (HR=1.57, 95%CI: 1.15-2.16, p=0.005). No statistical significance was observed for the risk of incident HS.

Conclusion:
In CRI patients elevated serum troponin levels were significantly associated with the risk of first time IS and higher all-cause mortality risk. The risk is further amplified significantly in females compared to males indicating sex differences play an important role in first time stroke risk in CRI. These findings represent an unexplored risk of IS.
Abstract WMP56: Genetics of Acute Ischemic Lesion Volume: the MRI-Genetics Interface Exploration (MRI-GENIE) Study
Authors: Giese Anne-Katrin , Xu Huichun , Schirmer Markus D , Donahue Kathleen L , Dalca Adrian V , Gaynor Brady J , Cole John W , McArdle Patrick F , Broderick Joseph P , Jimenez-Conde Jordi , Jern Christina , Kissela Brett M , Kleindorfer Dawn O , Lemmens Robin , Lindgren Arne , Rundek Tatjana , Sacco Ralph L , Schmidt Reinhold , Sharma Pankaj , Slowik Agnieszka , Thijs Vincent , Woo Daniel , Worrall Bradford B , Kittner Steven J , Meschia James F , Rosand Jonathan , Golland Polina , Mitchell Braxton D , Wu Ona , Rost Natalia S
Published: October 2018

Introduction:
Genome-wide association (GWA) studies have contributed substantially to the understanding of complex vascular traits including ischemic stroke; however, genetic determinants of acute cerebral ischemia remain to be elucidated.

Objective:
To investigate the genetic architecture of cerebral infarct lesion burden in patients with acute ischemic stroke (AIS).

Methods:
Twelve international sites contributed 3,301 AIS subjects with acute MRI and genome-wide genotyping to the MRI-GENIE study. In a preliminary analysis of 657 subjects of European ancestry, acute cerebral infarct lesions were outlined on diffusion-weighted images (DWI) using a semi-automated volumetric method. Standard quality control measures were performed per single nucleotide polymorphism (SNP) and per subject. SNPs were imputed to the Haplotype Reference Consortium v1.1 panel. Natural log-transformed DWI volume was used for GWA analysis with allelic dosage per SNP, age, sex and principal components 1-5 of genetic ancestry as covariates.

Results:
GWA testing for DWI volume in 7.7 million SNPs yielded no signal crossing the Bonferroni-corrected genome-wide significance threshold of
p
<5*10
-8
. However, several loci passed the nominal significance threshold of
p
<1*10
-6
(Figure 1), including a locus on chromosome 2 in the SPATA3-AS1 (spermatogenesis associated 3 antisense RNA 1) gene (lead SNP: rs2368999, MAF=36%,
p
=8.4*10
-7
) and an intronic locus on chromosome 10 in the ATRNL1 (Attractin like 1) gene (lead SNP: rs592284, MAF=10%,
p
=9.1*10
-7
).

Conclusion:
In this first-to-date, preliminary GWAS of acute cerebral infarct volume in AIS patients, we identified several new, nominally significant loci including a locus in ATRNL1, a gene previously linked to carotid plaque burden. Further analyses of the MRI-GENIE cohort to replicate these findings, to include stroke subtype specific analyses, and to increase the overall statistical power of the study are ongoing.
Abstract WMP59: Sleep Apnea is Associated with the Combined Endpoint of Recurrent Stroke and Post-Stroke Mortality
Authors: Brown Devin L , Li Chengwei , Chervin Ronald , Case Erin , Garcia Nelda , Morgenstern Lewis , Lisabeth Lynda
Published: October 2018

Introduction:
No data are available about the relationship between sleep apnea (SA) and recurrent stroke and mortality from population-based studies, large samples, or ethnically diverse populations.

Methods:
In the Brain Attack Surveillance in Corpus Christi (BASIC) project, we identified patients with ischemic stroke between 2010-2015. Subjects who enrolled were offered screening for SA with the ApneaLink Plus device from which an apnea-hypopnea index (AHI) was derived (≥10 defined SA). Demographics and baseline characteristics were determined from chart review and interview. Recurrent ischemic stroke was identified through active and passive surveillance and confirmed by study neurologists. All-cause mortality was identified through Texas Department of State Health Services records. Cox proportional-hazards models were used to assess the association between AHI (modeled linearly) and combined ischemic stroke recurrence and mortality unadjusted and adjusted for multiple potential confounders.

Results:
Of the 842 subjects, the median age was 65 (IQR: 57, 76), 47% were female, 58% were Mexican American, and 34% were non-Hispanic white. The median AHI was 14 (IQR: 6, 26); 63% had SA. SA was associated with male sex, Mexican American ethnicity, being insured, nonsmoking status, diabetes, hypertension, lower educational attainment, and higher BMI. In the time period (median time to event 584 days), 90 (10.7%) recurrent strokes and 125 (14.8%) deaths occurred with a cumulative incidence of recurrence or death of 202 (24%). AHI was associated with the combined endpoint in unadjusted (HR=1.09 per one unit increase in AHI (95%CI: 1.08, 1.10)) and fully adjusted models (HR=1.09 (95%CI: 1.08, 1.10)). Mexican American ethnicity was associated with the endpoint (HR=1.71 (95%CI: 1.16, 2.54) in the fully adjusted model.

Conclusion:
SA is associated with the combined endpoint of recurrent ischemic stroke and mortality in this population-based study. Mexican Americans are also at higher risk of recurrent stroke and death following ischemic stroke than non-Hispanic whites. SA may therefore represent an important modifiable risk factor for poor stroke outcomes and a target to reduce ethnic stroke disparities.
Abstract WMP61: Predictors of Diagnostic Yield of Implanted Loop Recorder in Patients With Cryptogenic Stroke: a Systemic Review and Meta-analysis
Authors: Bhatnagar Udit B , Sethi Prince , Gedela Maheedhar , Thompson Paul A , Pham Roman , Pham Scott
Published: October 2018

Background:
Implantable Loop Recorders (ILR) are increasingly being used for detection of atrial fibrillation (AF) after cryptogenic stroke (CS). There is limited data on determinants of diagnostic yield in this population.

Objective:
To systematically review prior available trials studying ILRs in CS to look for predictors of diagnostic yield of ILR over time.

Methods:
We searched MEDLINE and Cochrane Central Register of Controlled Trials. We included studies of ILRs on patients who presented with acute CS. We excluded studies which did not analyze baseline characteristics of patients with and without AF detection.

Results:
Our search revealed six prospective studies which met inclusion criteria with a total of 344 patients. All patients had at least 24 hour ambulatory EKG prior to ILR implantation. The mean duration of ILR monitoring was 445.2 days. On an average 24.4% of patients had new AF detected with an average time to detection of 85.5 days. Table 1 shows summary statistics and meta-analysis combinations of studies. Comparing covariates among patients with and without AF detection, a basic combination of individual study p-values (Z score) revealed age, CHADS-Vasc score, left atrial (LA) volume and ectopy to be significantly different in the two groups. Analyzing significance with χ
2
combination methods and combinations of effect size values suggested only CHADS-Vasc score to be significant. Ectopy was presented in terms of burden of APCs in two studies which showed significant difference between groups; and in terms of proportions of cases with “excessive” atrial ectopy in two other studies which did not show significance.

Conclusions:
Overall AF was detected in 24.4% of patients with ILR implantation after CS. CHADS-Vasc score was found to be a significant predictor in detecting AF. Older age, increased LA volumes and excessive ectopy on holter were found to be significant in some studies but on overall computation did not show statistical significance.
Abstract WMP63: Neuroimaging Findings and Incidence of Atrial Fibrillation on Follow-up in Patients With Embolic Stroke of Undetermined Source
Authors: Zurru Maria C , Balian Natalia , Alonzo Claudia , Brescacin Laura , Pigretti Santiago , Colla Machado Pedro , Luzzi Ariel , Camera Luis , Waisman Gabriel
Published: October 2018

Background and purpose:
paroxysmal AF is detected during follow-up in approximately 30% of ESUS. We aim to identify patterns of brain lesions suggestive of embolic events and to evaluate the incidence of AF during 4-years of follow-up.

Design and method:
acute ischemic stroke patients were prospectively included in a multidisciplinary secondary stroke prevention program. Cardioembolic stroke was ruled out with 12-lead ECG, 48-hour cardiac monitoring and transesophageal echocardiography. Large artery disease of intracranial and extracranial vessels was evaluated with MR or CT angiography or cervical duplex plus transcranial doppler ultrasonography. After this thorough evaluation, patients without cardioembolic or large artery disease and non-lacunar lesion on MRI were defined as ESUS.

Results:
479 (34%) of 1376 ischemic strokes included from September 2009 to December 2016 were ESUS; median age 78 years (IQR 69-84), 55% female. Pre-stroke VRF profile: 80% HT, 66% dyslipidemia, 14% DM, 51% obesity, 39% smoking, 34% CKD, 3% history of paroxysmal AF, 14% CHD and 10% previous stroke or TIA. Twenty-four patients (5%) died during hospitalization or within the next 30 days. There were 25 % (CI 95% 22-29) of recurrent strokes during 4-years of follow-up after stroke. The AF was detected in 15% of patients in the first year, 28% in the second year, 38% in the third year and 41% in the fourth year. Neuroimaging findings on-admission MRI are shown in the table.

Conclusion:
ESUS patients with AF during follow-up had higher incidence of hemorrhagic transformation during the acute phase as well as multiple lesions in different territories of the anterior and posterior cerebral circulation. As these findings are often seen in strokes of indubitable embolic origin the presence of these features should raise the suspicion of an underling embolic source.
Abstract WMP64: Atrial Dysfunction Markers Predicted AF in Elderly Cryptogenic Stroke Patients
Authors: Pagola Jorge , Juega Jesus , Bustamante Alejandro , Peñalba Anna , Gonzalvez Borja , Moniche Francisco , Escudero-Martinez Irene , de Torres Reyes , Cabezas Juan Antonio , Arenillas Juan Francisco , Usero Maria , De Lera Mercedes , Montaner Joan , Molina Carlos
Published: October 2018

Introduction:
Traditional predictors of paroxysmal AF (PAF) including left atria size, CHADSVASC score or rate of atria premature beats are inaccurate to predict PAF in elderly stroke patients. We aimed to evaluate the yield of atrial dysfunction markers such as NT-ProBNP and Left atrial deformability in acute elderly cryptogenic stroke patients to predict PAF.

Methods:
We prospectively evaluated cryptogenic stroke patients <72 hours from stroke symptoms. All patients underwent NT-ProBNP level measurement and left atrial strain (LAS) assessment by speckle tracking echocardiography. We performed a continuous wearable Holter monitoring from the admission up to 4 weeks after stroke.

Results:
Out of 150 cryptogenic stroke patients, one hundred and ten patients fulfilled 4 weeks of Holter monitoring. Median age was 75 years (69-83).The percentage of PAF detection was 24.5%. Age, sex, hypertension, diabetes, CHADSVASC score, NIHSSS, left atria volume, left ventricle ejection fraction and rate of atria premature beats were comparable between patients with and without PAF detection. Admission NT-ProBNP levels were higher (346.9 pg/ml [175-685]) in whom PAF was detected compared to those who did not (203.5 pg/ml [76.75-453.95] (p=0.028). Conversely, LAS was lower 18.66% [13.98-26.71] in PAF compared to no PAF detected patients 27.43% [21.28-36-56] (p=0.003). Both markers were inversely correlated (Spearman Rho -0.31) (p=0.007). The AUC of NT-ProBNP was 0.65 (0-53-0.76) with cut-off point of NT-ProBNP> 102 pg/ml (sensitivity 96%, specificity 33%) and LAS was 0.73 (0.59-0.86) with cut-off point of LAS <19.28% (sensitivity 50%, specificity 80.4%). The combination of both atrial dysfunction markers showed an AUC of 0.76 (0.69-0.88) with cut-off point of 0.23 (sensitivity 94%, specificity 50%).

Conclusions:
The combination of both NT-ProBNP and LAS markedly improve the predictive accuracy for PAF detection in elderly cryptogenic stroke patients.
Abstract WMP68: Clinical and Radiological Characteristics of Intracranial Artery Dissection Using Recently Proposed Diagnostic Criteria
Authors: Nakamura Yuki , Yamaguchi Yoshitaka , Koga Masatoshi , Morita Yoshiaki , Makita Naoki , Ide Toshihiro , Wada Shinichi , Shimohama Shun , Ihara Masafumi , Toyoda Kazunori
Published: October 2018

Background and purpose:
A group of international experts on intracranial artery dissection (IAD) recently reported a consensus statement and criteria about the diagnosis of IAD (Debette S, et al: Lancet Neurol 2015). But there are little data showing clinical features of IAD based on the new criteria. We aimed to elucidate clinical and radiological characteristics based on the criteria.

Methods:
Patients with suspected IAD were retrospectively enrolled using a prospective single-center stroke registry between 2011 and 2016. Baseline characteristics and radiological findings including conventional MRI sequences, MRA, 3D-T1 weighted TSE blood black (3DT1BB) sequence and digital subtraction angiography (DSA) were reviewed.

Results:
Of 147 patients with suspected IAD, 63 patients (15 women; mean age, 51±12 years) finally met the criteria of definite (n=47), probable (n=14) or possible (n=2) idiopathic IAD. Thirty-five (56 %) had a history of hypertension, 21 (33 %) had dyslipidemia, and 39 (62 %) had smoking habit. Ischemic stroke alone was found in 50 %, subarachnoid hemorrhage plus ischemic stroke in 6 %, TIA in 3 %, and head or neck pain alone in 41 % on admission. Vertebral artery was affected in 66 %, basilar artery in 2 %, posterior inferior cerebral artery in 5 %, anterior cerebral artery in 11 %, middle cerebral artery in 6 %, intracranial internal carotid artery in 2 % and multi-vessels in 8 %. Intimal flap, double lumen and aneurysmal dilatation were similarly observed between 3DT1BB and MRI/MRA/DSA. Intramural hematoma was more frequently detected in 3DT1BB sequence than conventional MRI/MRA (initial image, 53 % vs. 14 %, P < 0.001; follow-up image, 59 % vs. 22 %, P < 0.001). Follow-up image was essential to fulfill the criteria in 12 patients; rapid morphological change of aneurysmal dilation in 3, a newly detection of intramural hematoma in 3, double lumen in 2, pearl and string sign in 2, and aneurysmal dilation without change in morphology in 2 on follow-up images. Modified Rankin Scale score of ≤ 1 at 90 days was observed in 54 patients (86 %).

Conclusions:
Intracranial vertebral artery was most frequently affected. 3DT1BB sequence was apparently useful in detecting intraluminal hematoma in the recently proposed diagnostic criteria of idiopathic IAD.
Abstract WMP69: Imaging Analysis to Assess Stroke Mechanism in Aortic Dissection
Authors: Teleg Ericka Samantha , Menon Bijoy , Appoo Jehanggir , Fichdaya Akash , Mina Fady , Gregory Alex
Published: October 2018

Introduction:
Stroke is a frequent complication in patients having surgery for Acute Type A Aortic Dissection (ATAAD) where a variety of neurocirculatory techniques are used to reconstruct the arch. In order for surgeons to prevent stroke, first an understanding of the dynamic hemodynamic processes that cause stroke is required. Objective of this study is to determine radiological characteristics and mechanisms of stroke in ATAAD. So far, surgical literature has only reported on incidence.

Methods:
From 2006-2016, of 189 ATAAD patients at a single centre, 42 had a stroke. Charts and brain imaging were reviewed by 2 Neurologists. Great vessel pathology along with willisian collateral status was identified. Stroke territory (anterior or posterior circulation), distribution (unilateral or bilateral) and number of lesions were identified. Mechanism of stroke was classified as hypoperfusion (water-shed, borderzone pattern), embolic (cortical multiple or wedge shaped) or combined.

Results:
All strokes were ischemic. Mean patient age 60.1 +/- 13.1 years. Stroke was diagnosed a median 3.0 days (IQR = 5.1) post operatively. NIHSS classification was mild in 7%, moderate in 81% and 12% had severe. Most strokes were multiple (65%) and in the anterior circulation (88% vs. 32 % posterior). Most patients had an embolic pattern of stroke (45% vs. 36% hypoperfusion vs 17% mixed). Detailed clinical and radiologic data are shown in Table 1.

Conclusion:
Stroke after ATAAD is ischemic, predominantly embolic, involves both hemispheres and results in significant morbidity. It remains unclear if stroke is a result of the dissection disease process extending to the brain vs. iatrogenically caused by choice and methodology of intraoperative surgical neurocirculatory management strategies used to reconstruct the aorta. Further studies will look for associations between pre-operative cerebrovascular abnormalities, intra-operative management, and mechanisms of stroke.
Abstract WMP70: Yield of Screening Tests for Systemic Vasculitis in Ischemic Stroke in Young Adults
Authors: Yoon Cindy W , Rha Joung-Ho , Park Hee-Kwon
Published: October 2018

Background and Purpose:
The causes of ischemic stroke in young adults are more heterogeneous than in the elderly. Sometimes ischemic stroke in young adults is complicated by a systemic vasculitis, which can involve the brain. Therefore, a panel for systemic vasculitis could be considered as one of the etiological work-up of ischemic stroke in young adults. However, little is known about the yield of screening tests for systemic vasculitis in young ischemic stroke patients.

Methods:
Consecutive patients aged 18 to 45 years with ischemic stroke between January 2011 and June 2017 were included. They all underwent screening tests for systemic vasculitis including rheumatoid factor (RF), antinuclear antibody (ANA), antineutrophil cytoplasmic antibodies (ANCAs), anticardiolipin antibody, lupus anticoagulant, antiphospholipid antibody, anti-DNA antibody, and anti-Ro/SSA and La/SSB antibodies.

Results:
Among consecutive 2,938 acute ischemic stroke patients during study period, 177 patients (6.0%) were aged 18-45 years. The mean age was 39.0 years. Vasculitis panel screening results were positive in three patients (1.7%). They all had other symptoms or signs of systemic vasculitis. Two female patients with positive ANA and anti-DNA antibody were finally diagnosed as systemic lupus erythematosus (SLE). One patient was compatible with the diagnosis of anti-phospholipid antibody syndrome, and the other patient’s stroke was thought to be related to SLE vasculitis. They all had clinical symptoms of SLE including malar rash and Raynaud phenomenon. One male patient showed positive pANCA. A year previously, he was diagnosed with asthma. Inflammation markers in peripheral blood exams were elevated (CRP 8.21 mg/dl, leukocyte count 17.7/nl), the rate of eosinophilic cells increased (42%). He fulfilled the criteria for the diagnosis of Churg-Strauss syndrome.

Conclusions:
In the absence of systemic symptoms or signs of vasculitis, vasculitis panel screening in young ischemic stroke patients has a low yield. It’s better to consider individual clinical features and cost effectiveness before screening tests for systemic vasculitis in ischemic stroke in young adults.
Abstract WMP74: Therapeutic Effect of Human Dental Pulp Stem Cells Overexpressing Hepatocyte Growth Factor in Experimental Ischemic Stroke
Authors: Sowa Kota , Nito Chikako , Nakajima Masataka , Suda Satoshi , Nishiyama Yasuhiro , Takahashi Aki , Kasahara Yuko , Imagawa Kiwamu , Hirato Tohru , Ueda Masayuki , Okada Takashi , Kimura Kazumi
Published: October 2018

Objective:
Human dental pulp stem cell (DPSC) is an attractive cell source because they can be easily obtained as medical waste without ethical and logistical problems. Transplantation of DPSC decreases tissue injury in the rat brain and enhances motor function recovery after the middle cerebral artery occlusion (MCAO). We aimed increasing therapeutic effects combining DPSC and
ex vivo
human hepatocyte growth factor (HGF) gene transfer with adeno-associated virus (AAV) vector.

Methods:
Male Sprague-Dawley rats were subjected to transient 90 minute MCAO, followed by intravenous administration of 1 x 10
6
cells of DPSC, AAV-1/HGF transferred DPSC (DPSC/HGF) or vehicle immediately after reperfusion (each, n=8). Infarct volumes, neurological deficits and immunochemistry were assessed at 24 and 72 h after reperfusion. We also detected concentrations of TNF-α and IL-1β in the brain tissue extracts from the ischemic hemisphere by ELISA.

Results:
Infarct volumes at 24 h after reperfusion were diminished in both DPSC (155.7 ± 35.6 mm
3
, p < 0.01) and DPSC/HGF (110.2 ± 34.7 mm
3
, p < 0.01) transplantation compared with vehicle (213.1 ± 29.1 mm
3
). DPSC/HGF transplantation showed more reduction of infarct volume compared with DPSC (110.2 ± 34.7 mm
3
vs 155.7 ± 35.6 mm
3
, p < 0.05). Motor function recovery was also observed at 24 and 72 h by both DPSC and DPSC/HGF transplantation. Furthermore, we determined that DPSC/HGF transplantation significantly suppressed expression of Iba-1 and TNF-α compared with DPSC in the cortical ischemic boundary zone (p < 0.05, p < 0.01). Also, DPSC/HGF markedly decreased brain tissue TNF-α (11.5 ± 4.2 pg/ml) and IL-1β (22.2 ± 4.2 pg/ml) concentrations compared with vehicle (TNF-α, 54.6 ± 9.8 pg/ml, p < 0.01; IL-1β, 95.2 ± 9.8 pg/ml, p < 0.01) and DPSC (TNF-α, 26.8 ± 11.2 pg/ml, p < 0.05; IL-1β, 40.6 ± 11.2 pg/ml, p < 0.05) in the ischemic hemisphere. Both DPSC and DPSC/HGF group improved neuronal degeneration compared with vehicle (p < 0.05, p < 0.01).

Conclusions:
These findings show that overexpression of HGF by AAV vector would enhance the neuroprotective effects of DPSC transplantation through the modulation of inflammation after acute ischemic stroke.
Abstract WMP75: Functional Role of Hemojuvelin in Acute Ischemic Stroke
Authors: Tang Sung-Chun , Young Guang-Huar , Jeng Jiann-Shing
Published: October 2018

Background and Purpose:
Hemojuvelin (HJV)-hepcidin axis has been shown an important pathophysiological mechanism in acute liver and kidney injuries, but little is known about the role of HJV in acute stroke. Our aim was to establish the temporal expression and function of HJV during acute ischemic stroke (AIS).

Methods:
C57BL/6J mice receiving 1-hour middle cerebral artery occlusion (MCAO) and primary cortical neurons subjected to oxygen and glucose deprivation (OGD) were performed to determine the expression profile of HJV after AIS. Infarct sizes and behavior scores at 72 hours post MCAO on HJV knockout (129S-Hfe2tm1Nca/J) and wild type (129S) mice were compared to determine the role of HJV. In addition, patients with AIS were recruited and plasma samples were collected for the measurement of HJV.

Results:
The expression of HJV protein in mice brain was noted early at 3 hours after MCAO and increased significantly at 72 hours after MCAO, along with the appearance of its downstream protein- hepcidin at the same time point. In cultured cortical neurons, the expression of HJV protein also increased remarkably at 24-48 hours after 3 hours OGD stimulation. Importantly, HJV knockout mice had significantly less infarct size and expression of cleaved caspase-3 protein compared with wild type mice at 72 hours post MCAO. In human subjects, HJV expression can be seen in autopsy brain tissues from stroke patients with mortality outcome. In addition, among 112 AIS patients, plasma level of HJV within 48 hours after stroke was an independent poor prognostic predictor of functional outcome at 3 months post-stroke (odds ratio: 1.780; 95% confidence intervals: 1.032-3.073;
p
=0.038).

Conclusions:
HJV- hepcidin axis is existing in mice brain and participating in the mechanisms of post stroke neuronal injury. Clinically, plasma HJV may be a potential outcome indicator in patients with AIS.
Abstract WMP76: Post-Ischemic Accumulation of Ubiquitinated Proteins Induced by Free Radicals and Proteasomal Inhibition Promotes Cell Survival
Authors: Kahles Timo , Zhou Ping , Blanco Ismary , Qian Liping , Rodney-Sandy Reunet , Iadecola Costantino , Hochrainer Karin
Published: October 2018

Background:
Ubiquitination supports cell homeostasis and cell survival particularly under stress conditions, e.g. in the presence of reactive oxygen species (ROS). We previously found that focal cerebral ischemia leads to reperfusion-dependent ubiquitin aggregation. The mechanisms driving post-ischemic ubiquitination and whether it contributes to cell survival remain elusive. The proteasome, responsible for degradation of ubiquitinated proteins, is suppressed after ischemia, but it is unclear whether this contributes to ubiquitin accumulation. Here we investigate the relationship between post-ischemic ubiquitination, ROS and proteasome inhibition, and the impact of ubiquitination on post-ischemic cell fate.

Methods:
Organotypic hippocampal slices (HS) prepared from neonatal male C57BL6 mice underwent oxygen-glucose deprivation (OGD; 95%N
2
/5%CO
2
for 60 min followed by recovery) or H
2
O
2
treatment. Ubiquitination and ROS were assessed by Western blotting or dihydroethidium (DHE), respectively, and proteasome activity either by cleavable proteasome substrates or by an AAV-transfected GFPu reporter in live cells. Cell death was monitored with propidium iodide.

Results:
OGD increased ubiquitination at 60 min recovery (1.5±0.1-fold of normoxia (Nx), P<0.05, n=3-7), an effect not observed without O
2
during recovery, or in presence of ROS scavengers, suggesting involvement of ROS. Accordingly, H
2
O
2
-mediated ROS production also induced ubiquitination (1.8±0.2-fold of untreated, P<0.05, n=3-7). OGD suppressed proteasome activity by 49±3% (P<0.05, n=3) and augmented GFPu levels during recovery (1.13±0.03-fold of Nx, P<0.05, n=12), suggesting that post-ischemic proteasome inhibition contributes to ubiquitin accumulation. Finally, treatment with the E1 enzyme inhibitor PYR41 reduced OGD-induced ubiquitination by 51±5% and enhanced cell death (+23% at 24 hours, n=12-18), implying a protective effect of ubiquitination.

Conclusions:
We identify ROS and proteasome suppression as key players in regulating post-ischemic ubiquitination. Furthermore we establish for the first time that post-ischemic ubiquitination supports cell survival, a finding that may have implications for the development of novel stroke therapies.
Abstract WMP78: Brain Ischemia Induces Diversified Neuroantigen-Specific T Cell Responses That Exacerbate Brain Injury
Authors: Jin Wei-Na , Gonzales Rayna , Feng Yan , Wood Kristofer , Chai Zhi , Dong Jing-Fei , La Cava Antonio , Shi Fu-Dong , Liu Qiang
Published: October 2018

Background:
Autoimmune responses can occur when antigens from the central nervous system (CNS) are presented to lymphocytes in the periphery or CNS. However, whether autoimmune responses emerge after brain ischemia remains controversial. Similarly, it is debated whether genesis of autoimmune responses can impact outcome of ischemic stroke. We hypothesized that that brain ischemia can diversify T cell responses against CNS antigens, and that expanded CNS antigen-specific T cells can promote ischemic brain injury.

Methods:
We quantified the presence and status of T cells from brain slices of ischemic patients. Using a mouse strain that harbor a transgenic T cell receptor (TCR) to a CNS antigen, the myelin oligodendrocyte glycoprotein (MOG
35-55
) epitope (2D2), we determined the anatomic location and involvement of antigen presentation cells in the development of T cell reactivity after brain ischemia and how T cell reactivity impacts stroke outcome. Transient middle cerebral artery occlusion (MCAO) and photothrombotic stroke models were used in this study.

Results:
By coupling transfer of labeled myelin oligodendrocyte glycoprotein (MOG)
35-55
-specific (2D2) T cells with tetramer tracking, we show an expansion in reactivity of 2D2 T cells to MOG
97-108
and MOG
103-125
in transient MCAO and photothrombotic stroke models. This reactivity and T cell activation occur in the brain and not in the peripheral lymphoid organs after ischemia. Also, microglia act as antigen-presenting cells (APCs) that effectively present MOG antigen, and depletion of microglia ablates expansion of 2D2 reactive T cells. Notably, the adoptive transfer of neuroantigen-experienced 2D2 T cells exacerbates Th1/Th17 responses and brain injury. Finally, T cell activation and MOG-specific T cells can be seen in the brain of ischemic stroke patients.

Conclusion:
Our findings suggest that brain ischemia activates and diversifies T cell responses locally, which exacerbates ischemic brain injury.
Abstract WMP80: Cystathionine β Synthase Deficiency Exacerbates Cerebral Ischemia Reperfusion Injury Through Activation of the NMDA Receptor and Loss of Blood Brain Barrier Integrity in Mice
Authors: Gu Sean X , Sonkar Vijay , Kumar Rahul , Erland Arning , Bottiglieri Teodoro , Kruger Warren , Lentz Steven , Dayal Sanjana
Published: October 2018

Hyperhomocysteinemia is a risk factor for stroke; however the mechanisms by which elevated homocysteine leads to stroke are poorly defined. In a murine model of cystathionine β synthase (CBS) deficiency, we tested the hypothesis that mild to severe elevation in plasma total homocysteine (tHcy) increases susceptibility to cerebral infarction through N-methyl-D-aspartate (NMDA) receptor activation and is associated with altered permeability of the blood brain barrier. We studied male
Cbs
-/- mice conditionally expressing a zinc-inducible mutated human
CBS
(I278T) transgene along with
Cbs+/-
and
Cbs+/+
littermates at 10-14 weeks of age. The human transgene was allowed to express only until weaning to overcome the early mortality of
Cbs-/-
mice. A mild to severe increase in plasma total homocysteine levels (tHcy) were observed in
Cbs
+/- and
Cbs
-/- mice (6.1±0.3 and 309±18 μM respectively) compared with
Cbs+/+
littermates (3.1±0.6 μM, P<0.01). Experimental stroke was induced with middle cerebral artery occlusion for one hour followed by 24 hours of reperfusion. Both
Cbs
+/- and
Cbs
-/- mice exhibited significant increase in cerebral infarct size following ischemia-reperfusion (12.2±3% in
Cbs+/+
mice, vs 35.1±7.7% in
Cbs+/-
and 27.7±7.8% in
Cbs-/-
mice, P<0.05). BBB integrity was tested with Evan’s blue (EB) permeation, and a significant increase in EB extravasation was observed in
Cbs+/-
and
Cbs
-/- mice (3.8±0.8 and 4.8±0.2 EB/g respectively) compared to
Cbs+/+
mice (1.7±0.4 EB/g, P<0.05). Treatment for 2 weeks with a NMDA receptor antagonist (memantine) rescued
Cbs+/-
mice from cerebral ischemia reperfusion injury and reduced blood brain barrier permeability in
Cbs+/-
mice. These data provide evidence that both NMDA receptor activation and blood brain barrier disruption contribute to the mechanism of stroke in hyperhomocysteinemia and that modulation of the NMDA pathway may represent a novel therapeutic target.
Abstract WMP84: Immune Response Mediates Brain- Heart Interaction After Subarachnoid Hemorrhage
Authors: Yan Tao , Li Ran , Chopp Micheal , Chen Jieli
Published: October 2018

Background:
Cardiac dysfunction is evident after Subarachnoid Hemorrhage (SAH). Patients with cardiovascular complications after SAH have 3.5 times increased risk of death compared with non-cardiac complication SAH patients. The immune system may contribute to the cardiac pathological processes post-SAH.This study investigates the possible role of the immune system in mediating cardiac dysfunction after SAH in mice.

Methods:
Adult male C57BL/6J mice were subjected to SAH model or sham-control. The experimental groups includes (n=15/group): 1) Sham-control; 2) SAH alone; 3) SAH+splenectomy (SAH+SP). Splenectomy was performed one week before SAH. Cardiac hemodynamics and function were measured by echocardiography at 3 days after SAH. The Garcia behavior score was performed . Mice were sacrificed at the third day after SAH. Cardiac tissue immunostaining (n=10/group) and flow cytometry (n=5/group) were performed.

Results:
We found that: 1) SAH alone induces significant neurological deficit and vasospasm compared to sham-control. SAH+SP significantly decrease neurological deficit, but no significant improvement in the vasospasm compared to SAH mice (p<0.05). 2) SAH mice exhibit significant cardiac dysfunction identified by a decline cardiac ejection fractions (EF) and fraction shortening (FS) compared to the sham. SAH+SP significantly improves cardiac function by increasing EF and FS compared to SAH mice (P<0.05). 3) SAH significantly increases inflammatory cells (CD11b+/CD45+/F480+ macrophages) infiltration into the heart compared to sham-control (p<0.05). The amount of macrophages within the heart tissue was significantly decreased in SAH+SP group when compared with the SAH group. 4) MCP1 expression in the heart was significantly increased in SAH group compared to sham; SAH+SP significantly decreased MCP1 expression compared to SAH (p<0.05).

Conclusions:
SAH induces cardiac dysfunction; SAH with splenectomy decreases heart inflammatory cell infiltration, inflammatory factor expression as well as decreases cardiac dysfunction after SAH. Immune response may play an important role in SAH-induced cardiac dysfunction.
Abstract WMP86: Less Than Ideal: Trends in Cardiovascular Health Among US Stroke Survivors
Authors: Lin Amy , Lin Michelle P , Markovic Daniela , Ovbiagele Bruce , Sanossian Nerses , Towfighi Amytis
Published: October 2018

Background:
The American Heart Association defines ideal cardiovascular health through the achievement of seven medical and behavioral metrics, dubbed “Life’s Simple 7s” (LS7): abstaining from smoking; maintaining regular physical activity, normal body mass index, blood pressure, glucose, and total cholesterol levels, and eating a healthy diet. We previously reported poor cardiovascular health among US stroke survivors; however, recent prevalence and predictors of cardiovascular health remain unknown.

Objectives:
To determine the prevalence, pattern, and predictors of ideal LS7 among stroke survivors in the United States.

Design/Methods:
We analyzed prevalence and predictors of achieving ideal LS7 goals in a nationally representative sample of 1,597 US adults (≥18 years) with self-reported stroke, who participated in NHANES from 1988 through 2014. We assessed odds of low (0-1) vs. high (4+) LS7 scores according to sex, race, poverty income ratio (PIR), and education level, before and after adjusting for key sociodemographic and medical covariates.

Results:
Few participants (<1%) met all 7 ideal LS7 metrics. The proportion with low LS7 increased from 18% in 1988-1994 to 34% in 2005-2010 (p<0.001) where it remained stable. From 1988-1994 to 2011-2014, BP and cholesterol control improved (proportion with BP ≥140/90 mmHg decreased from 45% to 26% and cholesterol ≥240 mg/dL decreased from 37% to 10%); however, the proportion with obesity increased from 27% to 40%, prediabetes/diabetes increased from 49% to 56%, and healthy diet score >80% decreased from 22% to 1% (all p<0.05). After adjustment, those with low scores were more likely to be black (OR 2.41, 95% CI 1.22-4.76), have PIR ≤200% (OR 2.10, 95% CI 1.09-4.04), and have <12
th
grade education (OR 4.62, 95% CI 2.38-8.97).

Conclusions:
Fewer than 1% of US stroke survivors display ideal cardiovascular health. Although BP and lipid control has improved over the last three decades, rates of obesity, diabetes, and poor diet have increased. Stroke survivors who are black, socioeconomically disadvantaged, or less educated, have greater odds of having poor cardiovascular health, highlighting the need for targeted interventions
Abstract WMP89: Long-Term All-Cause Healthcare Costs for Stroke Differ by Stroke Severity
Authors: Milentijevic Dejan , Lin Jennifer H , Chen Yen-Wen , Bisht Deepti , Kogan Emily , Twyman Kathryn , Alberts Mark
Published: October 2018

Background:
While several studies have evaluated healthcare costs of stroke, limited data are available on long-term costs by stroke severity.

Objective:
To assess healthcare costs in relation to stroke severity over 3 years following stroke diagnosis.

Methods:
Patients with newly diagnosed stroke were assessed using OPTUM de-identified Integrated Claims-Medical Record Database (2007-2016). The National Institutes of Health Stroke Scale (NIHSS) score, imputed by 100 clinically relevant predictors selected by a random forest method, was used to group patients by severity: no impairment (<1, NI), minor (1-5, Min), moderate (>5-16, Mod), moderately severe (>16-21, MS), severe (>21-42, S). All-cause medical and pharmacy costs were estimated in patients for up to 3 years following diagnosis. Mean cumulative costs were evaluated by partitioning the follow-up period into 2-week intervals. The average cost incurred in each interval was then weighted by the Kaplan-Meier survival probability at the beginning of each interval, after which costs were summed across all intervals.

Results:
We identified 8512 patients with a mean age of 69 years at first stroke diagnosis; 1396, 4783, 1927, 215 and 191 were in the NI, Min, Mod, MS, and S cohorts, respectively. Mortality was 3%, 13%, 33%, 88% and 100% at Year 3 following stroke diagnosis in the NI, Min, Mod, MS, and S cohorts, respectively. In year 1 following diagnosis, the cumulative total healthcare costs were the highest in the Mod cohort (mean ± SE; $67365±$1234) and lowest in the S cohort ($15945±$647). Healthcare costs increased in year 3 substantially compared to year 1, with the NI cohort showing the greatest increase in healthcare costs (116% increase), followed by the Min (86%), Mod (39%), MS (9%) and S (0%) cohorts. Hospitalization was the costliest healthcare service across all cohorts and ranged in Year 3 from $62100 in the Mod cohort to $13241 in the S cohort; outpatient services were the second most costly.

Conclusion:
Majority of patients with severe strokes (MS and S) incurred high healthcare costs within a month whereas patients with less severe strokes (Min and NI) accrued more costs over time due to better survival outcomes, underscoring short and long-term economic burden of various degrees of stroke severity.
Abstract WMP9: Real-World Outcomes of Patients Presenting with Acute Ischemic Stroke >6 Hours Since Symptom Onset Treated With Endovascular Therapy
Authors: Beaulieu Marie-Claude , Karkri Fatine , Poppe Alexandre Y , Gioia Laura , Deschaintre Yan , Jacquin Grégory , Daneault Nicole , Stapf Christian , Odier Céline
Published: October 2018

Introduction:
Endovascular therapy(EVT) is proven effective for patients with acute ischemic stroke with proximal vessel occlusion, treated within 6 hours since symptom onset. However, up to 30% of stroke patients wake up with their symptoms (“wake-up stroke” (WUS)) or have an unknown time of onset. Canadian guidelines suggest that EVT may also be effective up to 12 hours after onset and yet-to-be published data from the DAWN trial also suggest a strong benefit of EVT for these patients if selected by perfusion imaging. We aimed to examine the real-world effectiveness of EVT in late-presenting stroke patients selected for EVT with a simple non-contrast CT (NCCT) and simple phase CT angiogram (CTA).

Methods:
We analyzed a prospectively collected registry of epidemiological, clinical and imaging data of patients treated for acute ischemic stroke ≥6 hours since symptom onset or WUS in a tertiary stroke center (Hôpital Notre-Dame, Montréal) between 2016 and 2017. Eligibility for EVT was based on a combination of disabling neurological deficit, a NCCT with salvageable brain tissue (ASPECTS >5), and presence of a LVO on CTA.

Results:
Over a 16-month period, a total of 366 patients were treated with IV thrombolysis and/or EVT. Of these, 46 had WUS or presented ≥ 6 hours since symptom onset and received EVT. Median age was 70, median baseline mRS score 1, median NIHSS at arrival 17 and median ASPECTS 9. Good collaterals on CTA were noted in 63%(29) of patients. 5 patients had posterior circulation stroke with basilar occlusion. Median time from last time seen normal to admission was 9h17(IQR, 6h44-12h46). 31 (67.4%) NCCTs were done at a referent center and not repeated locally to avoid treatment delays. At 3-month follow-up, functional autonomy(mRS
≤
2) was found in 15 (32.6%) patients while 15 (32,6%) died (mRS=6). Symptomatic hemorrhagic transformation occurred in 3(6.5%) patients.

Conclusions:
In a real-world setting, EVT is feasible in late-presenting stroke patients selected by NCCT and yields favorable outcomes similar to those seen in the more pragmatic EVT trials.
Abstract WMP91: Post-Stroke Healthcare Utilization: Patterns in Stroke Follow-up Care in a Community Hospital System - A Preliminary Analysis From the Greater Cincinnati/Northern Kentucky Stroke Study
Authors: Buchberger David , Sucharew Heidi , Alwell Kathleen , Moomaw Charles J , Haverbusch Mary , Woo Daniel , Flaherty Matthew L , Demel Stacie L , Ferioli Simona , Mackey Jason , De Los Rios La Rosa Felipe , Walsh Kyle , Gillow Sabreena , Star Michael , Kleindorfer Dawn O , Kissela Brett
Published: October 2018

Introduction:
Immediate post-stroke discharge destination is easily determined. Long-term disposition and healthcare utilization is more difficult to study due to the variability in outcomes, including multiple transitions for many patients. We sought to longitudinally determine place of residence and physician follow-up in a defined population.

Methods:
Our population-based stroke epidemiology study retrospectively ascertains hospitalized ischemic and hemorrhagic strokes via ICD-9/10 codes within 5 counties in the greater Cincinnati metropolitan region. For this study, post-stroke dispositions and physician encounters for ischemic strokes that presented to one healthcare system of 4 community hospitals from 1/1/15 to 12/31/15 were analyzed by mining patient electronic medical records (EMRs). Disposition was analyzed at discharge, 3, and 6 months post-stroke, and outpatient and emergency department (ED) visits, and hospital admissions, were tabulated at 3, 6, and 12 months. The first post-discharge physician encounter was also assessed, and time to encounter was considered. Previous analysis has shown that this network is relatively self-contained with few transfers to other health systems, making it ideal for this study.

Results:
See figure for details. Only 17% of the cohort saw a neurologist within 1 year, whereas 73% saw a primary care provider (PCP) and 37% saw a cardiologist. PCPs accounted for 56% of the first post-stroke encounters. Over 24% of the cohort visited the ED or were re-hospitalized before having their first outpatient visit.

Conclusions:
In a community setting, PCPs are responsible for the majority of post-stroke care, and fewer than one in five patients sees a neurologist post-stroke. Future work will include additional analysis to determine whether the results from this health system are consistent with others in our region.
Abstract WMP92: Towards High-Precision Stroke Classification Using Natural Language Processing
Authors: Majersik Jennifer J , Mowery Danielle , Zhang Mingyuan , Hill Brent , Cannon-Albright Lisa A , Chapman Wendy
Published: October 2018

Introduction:
Case identification for genetic epidemiologic stroke studies relies upon diagnostic codes or laborious hand-adjudication. Natural language processing (NLP) can extract discerning characteristics of a patient phenotype from clinical texts to support high-precision phenotyping. In this pilot study, we aimed to support large-scale analysis of stroke pedigrees by developing an NLP algorithm to accurately identify stroke patients from the electronic health record.

Methods:
We randomly sampled 500 stroke cases (400 ischemic, IS, and 100 hemorrhagic, HS) and 100 non-stroke neurologic controls from a neuroICU database; 2 content experts validated diagnoses. We divided the dataset into train (n=400) and test (n=200) sets and applied 5-fold cross validation analyses to the train set. We leveraged 2 text-processing approaches: n-grams (creating word features of 1-4 word window lengths from clinical notes, e.g., 1-gram = “tpa”) and NLP that adds ConText to n-grams (e.g.,
negation
). In both approaches, we applied feature selection to identify the most informative n-grams (top 1% ranked by X
2
) associated with the diagnoses. We trained each classifier using varying note types: 1) radiology, 2) radiology + discharge, 3) radiology + discharge + others and report mean positive predictive value (PPV) for IS vs HS/Other and HS vs IS/Other, using a) n-grams and b) NLP.

Results:
Using n-grams alone, there was consistently high PPV for discerning all Stroke vs Other for all text sources (Figure). N-gram PPV improved dramatically for IS vs HS/Other by adding more note types. NLP consistently out-performed n-grams alone, with high PPV for all Stroke vs Other and for IS vs HS/Other. Both approaches performed poorly for HS vs IS/Other.

Conclusions:
NLP is a promising method to accurately phenotype stroke cases. Determining the optimal number of notes required will allow for more streamlined data processing. Future work will focus on improving discrimination of HS vs IS/Other.