bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP124: Comparison of Stent Placement With Best Medical Treatment in Patients With Vertebral Artery Stenosis: A Meta-analysis of Randomized and Non-randomized Studies
Authors: Pandhi Abhi , Ishfaq Ammad , Ishfaq Muhammad F , Ahmed Sundas I , Deep Aman , Singh Savdeep , Qureshi Adnan I
Published: October 2018

Background:
Although offered at many centers, there is lack of evidence regarding whether stent placement is superior to best medical treatment for patients with vertebral artery stenosis in preventing new or recurrent brain ischemic events.

Methods:
Three randomized controlled trials (RCTs) and 1 non randomized comparative study were included. We calculated pooled risk ratio (RR) and 95% confidence intervals (CI) using random effect model. End points were major adverse events including stroke, myocardial infarction (MI) or vascular events within 30 days, new stroke in vascular territory of target vertebral artery; and all cause mortality in follow up period.

Results:
Of the 352 subjects (136 underwent stent placement) analyzed, 26 patients (7.4%) had stroke in the vascular territory of target vertebral artery. The risk of stroke in the vascular territory of target vertebral artery was not significantly different between the two groups (RR = 1.00; 95% CI 0.37-2.70; P =0.99). The risk of major adverse events including stroke, MI, and/or vascular events was non-significantly higher in patients who underwent stent placement (RR 2.62, 95% CI 0.56 - 12.19, p=0.22). No significant difference in all cause mortality was identified between the two groups on follow up at 3 years (RR 1.03, 95% CI 0.61-1.75, p=0.91).

Conclusion:
We did not identify any reduction of stroke in Vascular territory of target vertebral artery in our analysis. Further studies are needed to ensure that stent placement performed in current practice is actually efficacious in patients with vertebral artery stenosis.
Abstract WP149: Women on Hrt With Ischemic Stroke, a Positive Effect on Deficits and Recovery?
Authors: Wells Jordan , Brown Aliza T , Bryant-Smith Gwendolyn , Onteddu Sanjeeva , Joiner Renee , Morgan Tiffany , Benton Tina , Culp William , Lowery Curtis
Published: October 2018

Background:
Hormone replacement therapy (HRT) for post-menopausal women is associated with increased incidence of ischemic stroke risk. Effects of HRT on stroke related deficits and functional outcomes in acute ischemic stroke (AIS) are uncertain. We retrospectively examined female consult data for HRT use and National Institutes of Health Stroke Score (NIHSS) at baseline and recovery for 2015 and 2016 in a large stroke telemedicine program.

Hypothesis:
The age of women on HRT will affect stroke severity and outcomes.

Methods:
We analyzed consult data from two consecutive years for women HRT use, age, and baseline and 24 hour NIHSS’s. We included all treated with IV Activase.

Results:
In two years 235 women received Activase therapy. Women without HRT use numbered 208 and 27 women listed HRT use. All 235 consults regardless of HRT use had significantly improved 24 h NIHSS vs. baseline (7.5 +/- 0.5 vs. 11.2 +/- 0.5, p<0.0001). Women on HRT had significantly improved 24 h NIHSS vs. baseline, (4.9 +/- 1.6 vs. 8.4 +/- 1.2, p=0.0084). Composite NIHSS’s at 24 h for ‘No HRT’ was not different from ‘Yes HRT’ (7.8 +/- 0.6 vs. 4.9 +/- 1.6, p=0.084) when groups included all women regardless of age. The baseline NIHSS’s when divided into specific age ranges showed decreased values when on HRT from 50s through 70s (
figure A
) p=0.028. Women placed in decade age ranges showed that 24 h NIHSS’s (40-80 years) with HRT use were lower vs. women >80 years (
figure B
). p=0.084.

Conclusion:
While controversy persists on the use, route and dosage of HRT for risks of ischemic stroke, positive HRT benefits could include moderation of AIS deficits and improved outcomes in women <80 years of age. Further study is needed.
Abstract WP155: Diabetes Predicts for Poor Long-term Functional Outcome After Acute Ischemic Stroke
Authors: Huang Ian , Allen John C , Ng Szu Chyi , De Silva Deidre A
Published: October 2018

Background:
Stroke and diabetes are important causes of disability. The impact of diabetes on long-term functional outcomes after stroke is unclear. Our primary aim was to compare functional outcomes periodically over 7 years between diabetic and non-diabetic ischemic stroke patients. We also investigated the impact of diabetes on the long-term trajectory of functional outcomes, and the influence of age on the diabetes-functional outcome association.

Methods:
This is a longitudinal observational cohort study of 802 acute ischemic stroke patients recruited from a tertiary hospital in Singapore from 2005 to 2007. Functional outcomes were assessed using the modified Rankin Scale (mRS) with poor functional outcome defined as mRS ≥ 3. Follow-up data was determined at 6 months, a median of 29 months and 86 months.

Results:
Among the 802 ischemic stroke patients studied, 45% were > 65 years old and 42% had diabetes. Diabetic patients were more likely to have poor functional outcomes at 6 months (OR = 2.122, 95% CI: 1.226-3.673), and at median follow-up durations of 29 months (OR = 1.957, 95% CI: 1.366-2.814) and 86 months (OR = 2.269, 95% CI: 1.583-3.253), after adjustment of covariates. Diabetes was not an interaction factor for both mRS distribution and poor functional outcome when comparing between the various follow-up time-points. There was a significant interaction between age and diabetic status in terms of poor functional outcome in the long-term.

Conclusion:
Diabetes is a prognostic factor for poor functional outcomes after ischemic stroke; its impact remained consistent throughout the 7-year follow-up period and was influenced by age in the long-term.
Abstract WP156: A Phase IIa Double-blind, Placebo Controlled Study of Extended-release Niacin for Stroke Recovery
Authors: Russman Andrew N , Silver Brian , Katramados Angelos , Chopp Michael , Burmeister Charlotte , Schultz Lonni , Mitsias Panayiotis
Published: October 2018

Introduction:
In pre-clinical studies, extended-release niacin has been shown to increase neurogenesis, synaptogenesis, and angiogenesis in a rat model of experimental middle cerebral artery (MCA) occlusion. Using this animal model, extended-release niacin has been shown to improve functional outcomes in rats when compared to placebo, beginning 24 hours after experimental stroke.

Methods:
This was a phase IIa double-blind, randomized, placebo controlled study (Henry Ford Health System funded; clinicaltrials.gov NCT00796887). At a single site (Henry Ford Hospital, Detroit, MI), patients with ischemic stroke 3 to 7 days prior and NIHSS 4-20 were randomized to two doses of oral extended-release niacin (500 mg or 1000 mg daily) or placebo. Primary outcome measures were change in mRS or NIHSS from baseline to Week 24.

Results:
There were 27 patients enrolled in this study. Ten patients were randomized to extended-release niacin 500 mg, 7 to 1000mg, and 10 to placebo. No significant differences were seen in baseline characteristics of enrolled patients. Significant increases in HDL-C were seen from baseline to 24 weeks among extended-release niacin treated patients (12.5 mg/dL, p=0.035), but not in placebo-treated patients (6.2 mg/dL, p=0.157). Mean improvement in NIHSS from baseline to 24 weeks of treatment was similar for both extended-release niacin and placebo treated patients (6.5 vs. 6.1, p=0.845). No differences were seen in functional outcome (mRS) at 24 weeks between extended-release niacin and placebo treated patients (2.1 vs. 2.0, p=0.860). There were a total of 40 AEs, with 27 in the extended-release niacin group and 10 in the placebo group. For these AEs, no clear interaction with treatment group could be confirmed.

Conclusions:
Extended-release niacin administered for 24 weeks starting between 3 and 7 days after ischemic stroke demonstrated no improvement in functional outcome as compared to placebo. Extended-release niacin was overall well tolerated. Although this small exploratory study did not identify a signal for potential efficacy, useful sample size estimates were gleaned. Any future clinical investigations may benefit from the collection of additional clinical measures of motor or gait function to differentiate treatment effects.
Abstract WP160: Exome Array Analysis of Early-Onset Ischemic Stroke
Authors: Cole John W , Jaworek Thomas , Ryan Kathy , Gaynor Brady , McArdle Patrick , Stine Oscar C , Aparicio Hugo J , Gao Yan , Lin Xiaochen , Grove Megan L , Kittner Steven J , Wilson James G , Yang Qiong , Seshadri Sudha , Lui Simin , Mitchell Braxton D , Xu Huichun
Published: October 2018

Background:
The genetic architecture of ischemic stroke (IS) is poorly understood and may differ by age of onset. To identify stroke susceptibility variants, genes and pathways for IS in young adults, we genotyped participants in the Genetics of Early-Onset Stroke (GEOS) with an exome array to interrogate the protein-coding portion of genes.

Methods:
The GEOS Study was initiated as a biracial population-based study of cases with first-ever ischemic stroke 15 to 49 years of age (n=828) and controls (n=850). All participants had prior GWAS and underwent Illumina exome-chip genotyping. Mixed model regression in EMMAX was conducted to calculate variant-specific associations using pooled European-Caucasians (EUR) and African-Americans (AA) samples, with population structure controlled by kinship matrix relationships using GWAS data. Gene-based burden testing and meta-analysis were performed using seqMeta with ethnicity-specific GWAS PCs. In both analyses covariates included age and gender. This was followed by Ingenuity Pathway Analyses on the top genes.

Results:
While no individual SNPs reached chip-wide significance (3x10
-7
), several were near, including one exonic variant in
TRAPPC11
(rs67383011, p=1.7*10
-6
). Gene-based burden testing using a filter (cumulative MAC>40, # of SNPs per gene≥2, missingness=0) was performed on 6934 genes in EURs and 9423 genes in AAs. While several interesting genes were identified, notably in methylation pathways, none reached statistical significance in the ethnicity-stratified (p=3.3*10
-4
) or meta-analyses (p=1.1*10
-4
). Pathway analyses on the top 448 genes (p<0.05) from the gene-based results identified several metabolism and signaling pathways, including: (1) those implicated in the risk for vascular diseases: glucose metabolism, lipid metabolism, and inflammation (leukocyte extravasation, IL-17A); (2) neurotrophic signaling: CTNF and NGF, and; (3) neurotransmitter and neuroactive compound signaling: GABA receptor signaling and tryptophan degradation pathways. Efforts in additional data sets to replicate these findings are ongoing.

Conclusion:
Exome-based analyses in the setting of early-onset stroke is a promising methodology to identify novel genetic risk variants, loci and pathways.
Abstract WP161: Pancreatic Beta Cell Function and Prognosis of Nondiabetic Patients With Ischemic Stroke
Authors: Pan Yuesong , Chen Weiqi , Wang Yongjun , He Yan , Wang Yilong
Published: October 2018

Background and Purpose:
Pancreatic β-cell dysfunction is an important factor in the development of type 2 diabetes. This study aimed to estimate the association between β-cell dysfunction and prognosis of nondiabetic patients with ischemic stroke.

Methods:
Patients with ischemic stroke without a history of diabetes in the Abnormal Glucose Regulation in Patients with Acute Stroke across China (ACROSS-China) registry were included. Disposition index (DI) was estimated as computer-based model of homeostatic model assessment (HOMA2)-β%/ HOMA2-IR based on fasting C-peptide level. Outcomes included stroke recurrence, all-cause death and poor outcome (modified Rankin Scale 3-6) at 12 months after onset.

Results:
Among 1171 patients, 37.2% were female with a mean age of 62.4 years. At 12 months, 167(14.8%) patients had recurrent stroke, 110(9.4%) died, and 294(25.6%) had a poor outcome. The first quartile of the DI was associated with an increased risk of stroke recurrence (adjusted hazard ratio [HR] 3.57, 95% confidence interval [CI] 2.13-5.99); both the first and second quartiles of the DI were associated with an increased risk of death (adjusted HR 5.09, 95% CI 2.51-10.33; adjusted HR 2.42, 95% CI 1.17-5.03) and poor outcome (adjusted odds ratio [OR] 3.83, 95% CI 2.27-6.48; adjusted OR 2.06, 95% CI 1.25-3.42) compared with the fourth quartile. Using a multivariable regression model with restricted cubic spline, we observed an L-shaped association between the DI and the risk of each endpoint.

Conclusions:
In this large-scale registry, β-cell dysfunction was associated with an increased risk of 12-month poor prognosis in nondiabetic patients with ischemic stroke.
Abstract WP168: Socioeconomic Status and Stroke Severity
Authors: Selvik Henriette Aurora , Naess Halvor , Kvistad Christopher Elnan
Published: October 2018

Background:
Stroke has been shown to disproportionately strike those of lower income, either inhabitants of low-income countries, or low-income groups within high-income countries. Norway is a social democratic welfare state where every citizen has the same access to health care services, including acute stroke treatment. The aim of this prospective study was to assess if stroke severity and short-term functional outcome is affected by socioeconomic status (SES).

Methods:
All ischemic stroke patients admitted to the stroke unit at Haukeland University Hospital, Norway, between February 2006 and December 2008 were sent a questionnaire 6 months after stroke ictus. The questionnaire included information regarding SES as well as subjective opinion of quality of life post stroke. SES data was self-reported and included gender, age, marital status, education, individual net income and occupation. Stroke severity was determined by use of National Institutes of Health Stroke Scale Score (NIHSS) on admission and short-term functional outcome was defined using the modified Rankin Scale (mRS) score on day 7 after ictus. NIHSS and mRS were dichotomized in high/low depending on their mean values; respectively NIHSS score ≤ 6 / > 6 and mRS score ≤ 2 / > 2. Logistic regression was chosen for multivariate analysis and SES factors (income, education and marital status) were forced into all regression models.

Results:
A total of 328 patients with ischemic stroke were included in the study; mean age was 67.7 years (SD 13.3) at the time of stroke ictus, and 63 % were male. Patients with a high net income were more often married (
P
< .01 ) than those of lower income, and as expected, had a higher level of education (
P
< .001 ). On logistic regression analysis lower net income level was the only SES factor associated with a more severe stroke (
OR
= 0.64,
95 % CI
0.44 - 0.92,
P
= 0.02). SES did not affect short-term functional outcome.

Conclusion:
Preliminary results show that lower net income predicts a more severe stroke. This was found in a Norwegian stroke population despite equal access to health care services and free education for all citizens.
Abstract WP170: Chronic Kidney Disease as a Risk Factor for Enlarged Perivascular Spaces, and Relation to Racial Group
Authors: Penton Ashley , Lau Helena , Babikian Viken L , Greer David , Aparicio Hugo , Nguyen Thanh , Cervantes-Arslanian Ana , Mercado Melissa , Beesen Ayshe A , Takahashi Courtney , Romero Jose R
Published: October 2018

Purpose:
Enlarged perivascular spaces (EPVS) are brain MRI markers of subclinical small vessel disease (SVD). Recent studies suggest that basal ganglia (BG) EPVS represent hypertensive vasculopathy, while centrum semiovale (CSO) EPVS represent cerebral amyloid angiopathy. Increasing evidence links chronic kidney disease (CKD) to SVD, but the relation to EPVS topography has not been studied, and data are lacking among racial groups. In this study, we explore the relationship between CKD and burden of EPVS across racial groups.

Methods:
We included 894 consecutive stroke patients who underwent brain MRI admitted to an academic stroke center. EPVS were rated in the BG, and CSO following a standardized method, where severe burden of EPVS is considered when counts are 20 or greater. Race was assessed by self-report based on US census procedures and categorized as White, Black or Other racial groups (ORG). CKD was defined by past medical history or GFR < 60mL/min/1.73m
2
. We used multivariable logistic regression analysis to relate CKD and EPVS severity (mild [<20] vs severe [20 or greater]), adjusting for age, sex, hypertension, smoking and diabetes.

Results:
CKD was present in 22% of the sample, in 17.7% Whites, 27.9% Blacks and 13.2% ORG. Severe EPVS prevalence for Whites, Blacks and ORG was for BG 19.6%, 18%, and 15.4%; and for CSO 38.8%, 42.6%, and 33.6%, respectively. In multivariate analysis, CKD was associated with severe EPVS in the CSO in the entire sample (OR 1.39, 95% CI 1, 1.94). The relation differed depending on EPVS topography and racial group. For BG, Whites had lower odds of severe EPVS compared to Blacks and ORG (OR 0.33, 9%% CI 0.12, 0.95), while for CSO, Whites with CKD had higher odds of severe EPVS (OR 2.18, 95% CI 1.03, 4.63).

Conclusion:
CKD was associated with severity of EPVS in our sample of stroke patients. The relation differed across racial groups and by EPVS topography, suggesting that CKD may relate differently to the main forms of SVD (hypertensive and cerebral amyloid angiopathy) according to race. In Whites, the strong association of CKD with EPVS severity in the CSO may result from impaired amyloid clearance, but this hypothesis requires further study.
Abstract WP172: Stroke Incidence and Outcomes in Northeastern Greece: the Evros Stroke Registry
Authors: Tsivgoulis Georgios , Patousi Athanasia , Pikilidou Maria , Birbilis Theodosis , Katsanos Aristeidis H , Mantatzis Michael , Asimis Aristeidis , Papanas Nikolaos , Skendros Panagiotis , Terzoudi Aikaterini , Zebekakis Pantelis , Maltezos Efstratios , Piperidou Charitomeni , Vadikolias Konstantinos , Heliopoulos Ioannis
Published: October 2018

Introduction:
Data are scarce on both stroke incidence rates and outcomes in Greece and in rural areas in particular. We performed a prospective population-based study evaluating the incidence of first-ever stroke in the Evros perfecture, a region of a total 147,947 residents located in North Eastern Greece.

Methods:
Adult patients with first ever stroke were registered during a 24-month period (2010-2012) and followed up for 12 months. To compare our stroke incidence with that observed in other studies, we standardized our incidence rate data according to the European Standard Population (ESP) of 2013 and applied criteria of data quality, as proposed by the Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) project. Stroke diagnosis and classification was performed using WHO criteria on the basis of neuroimaging and/or autopsy data.

Results:
We prospectively documented 703 stroke cases (mean age: 75±12 years; 52.8% males; ischemic stroke (IS): 80.8%, intracerebral hemorrhage (ICH): 11.8%, subarachnoid hemorrhage (SAH): 4.4%, undefined: 3.0%) with a total follow-up time of 119,805 person-years. The unadjusted and ESP adjusted incidences of all strokes were 586.8 (95%CI: 543.4-630.2) and 534.3 (95%CI: 532.3-536.3) per 100,000 person-years, respectively. The unadjusted incidence rates for IS, ICH and SAH were 474.1 (95%CI: 435-513), 69.3 (95%CI: 54-84) and 25.8 (95%CI: 25.7-25.9) per 100,000 person-years, respectively. The corresponding ESP-adjusted incidence rates per 100,000 person-years were 425.9 (95%CI: 424-427), 63.3 (95%CI: 63-63.5) and 25.8 (95%CI: 25.7-25.9) for IS, ICH and SAH, respectively. The overall 30-day case fatality rate was 21.3% (95%: 18.3-24.4%) for all strokes, and was higher in hemorrhagic strokes than IS (40.4%, 95%CI: 31.3-49.4% vs 16.2%, 95%CI: 13.2%-19.2%).

Conclusion:
This is the largest to date population-based study in Greece documenting one of the highest stroke incidences in South-Eastern Europe.
Abstract WP174: Factors Associated With Medication Knowledge Among Stroke Survivors
Authors: Park Ji Hyun , Goldmann Emily , Parikh Nina S , Appleton Noa , Boden-Albala Bernadette
Published: October 2018

Introduction:
Adequate medication knowledge among stroke patients has been shown to be associated with a reduction in vascular risk factors and recurrent stroke. Yet, limited research has investigated the clinical and sociodemographic factors associated with adequate medication knowledge among stroke survivors.

Methods:
The Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) trial was an RCT of a skills-based educational intervention in a multi-ethnic cohort of mild stroke/TIA patients. As part of the trial, patients randomized to the intervention arm were called 72 hours post-discharge and asked about their knowledge of the discharge medications reported in their medical record. They received 1 point each for correctly reporting the name, purpose and dosage of the medication; medication knowledge scores ranged from 0 to 3 for each medication. For each patient, medication knowledge scores were averaged across all of their medications, and the average score was categorized as “adequate” (score ≥ 2) and “inadequate” (score < 2). Multivariable logistic regression analysis was used to evaluate the independent associations between having adequate medication knowledge and select sociodemographic and clinical factors measured pre-discharge.

Results:
A total of 235 patients were included in the analysis. On average, patients were able to accurately recall 50% of their medication names, 57% of their medication purposes, and 39% of their medication dosages. Thirty-seven percent had adequate medication knowledge. In the adjusted model, the odds of having adequate medication knowledge was higher for patients taking less than 5 medications vs. those taking 11 medications or more (odds ratio [OR]: 9.99; 95% confidence interval [CI]: 4.01-24.88), patients younger than 60 years vs. those 60 years or older (OR: 2.05; 95% CI: 1.10-3.80), and patients who had no stroke history vs. those who previously had a stroke (OR: 2.66; 95% CI: 1.25-5.64).

Conclusion:
Understanding the factors associated with medication knowledge among stroke survivors can help tailor discharge education plans to maximize medication adherence and improve stroke outcomes.
Abstract WP177: Alcohol Consumption: Benefit versus Harm in Vascular Events and Overall Mortality
Authors: Kim Do Yeon , Jeong Han-Gil , Kim Chi Kyung , Yang Wookjin , Kang Dong-Wan , Park Eun Sun , Lee Seung-Hoon
Published: October 2018

Background:
Alcohol consumption is associated with negative consequences including liver disease, major trauma and various cancers. However, a paradoxical beneficial effect of alcohol has been documented for cardiovascular disease in a large meta-analysis. On the other hand, a similar relationship has not been consistently documented or modest for the risk of stroke due to its heterogeneity in subtypes and pathophysiology. In this context, more comprehensive approaches using a representative dataset and composite outcomes are required to clarify the differential effects of alcohol on cardio-cerebrovascular disease (CCVD).

Methods:
The Korean National Health Insurance Service (NHIS) is the sole provider of full-coverage health insurance for Korean citizens. NHIS-National Sample Cohort (NHIS-NSC) was a standardized cohort representative of Korean population. Based on biennial health exam at 2003 and 2004, we investigated the relationship between alcohol consumption and the incidence of CCVDs [ischemic stroke (IS), hemorrhagic stroke (HS) and myocardial infarction (MI)] and all-cause mortality until 2013, using multivariable Cox proportional hazards models.

Results:
Among 204,557 participants (median follow up, 9.1 years), the following events were observed: IS 3,274; HS 1,056; MI 1,065 ; and all-cause mortality 8,771 cases. The hazards for IS and MI remained below the null point for the moderate alcohol consumption, but the risk for HS increased in heavy drinkers. In composite outcome indices, moderate consumption was associated with a lower risk for CCVD and all-cause mortality; however, the risk for all-cause mortality was significantly elevated in cases of heavy drinkers.

Conclusions:
Alcohol consumption was associated with a decreased risk of both CCVD, specifically ischemic vascular disease, and all-cause mortality at moderate dose, but this protective relationship was offset by an increase in the risk for HS and mortality at heavy dose.
Abstract WP185: The Influence of Diabetes on Subtype, Treatment and Outcome in Stroke Patients in Scotland
Authors: Sterling Kadie-Ann , Turner Melanie , MacLeod Mary J ,   Scottish Stroke Care Audit
Published: October 2018

Background:
Diabetic patients are at a higher risk of stroke than non-diabetic patients. However, the consensus of the effect of diabetes on stroke prognosis is still ongoing.

Aims:
This study aims to investigate whether diabetes influences the type, treatment and mortality outcomes in stroke patients in Scotland using the Scottish Stroke Care Audit.

Methods:
The Scottish Stroke Care Audit was used to identify 58,099 stroke cases in Scotland from January 2005 to December 2013. Baseline characteristics, stroke subtypes, six simple variable (SSV) assessment scores, acute treatment and mortality outcomes were examined in persons with and without a corresponding diabetes diagnosis in hospital coding. Statistical tests were used to compare these characteristics in the two groups, with logistic regression and cox-proportional hazards to evaluate the odds ratios and hazard ratios for mortality outcomes up to one year after first time stroke event.

Results:
The Scottish Stroke Care Audit stroke population included 6119 (10.5%) with a hospital based code of diabetes. These patients had significantly more ischaemic strokes and less haemorrhagic strokes than non-diabetic patients (P < 0.0001), they also had better SSV scores indicating less severe strokes. Diabetic patients were less likely to receive thrombolysis for ischaemic stroke (P = 0.001), but were more likely to be given aspirin (P < 0.0001), with both groups treated similarly with antiplatelet therapy in-hospital (P = 0.566), and anticoagulant therapy upon discharge (P = 0.247). Less diabetic patients died up to 9 months after stroke, but at one year the mortality cases were similar in both groups (P = 0.061). Diabetes was not an independent risk factor for mortality, but when the cox proportional hazard model was adjusted for age, gender, stroke subtype and SSVs, the mortality risk increased in diabetics with HR 1.06 (95% CI: 1.01 - 1.12, p = 0.018)

Conclusions:
Diabetes impacts on the type, treatment and mortality outcomes in stroke patients in Scotland, with a predisposition for milder ischaemic strokes in this group. As diabetes increases the risk of recurrent strokes, improving treatment of even mild events may reduce disease burden longer term.
Abstract WP187: Diagnostic Significance of Connective Tissue Dysplasia Signs in Patients With Cervical Artery Dissection
Authors: Gubanova Mariia , Kalashnikova Ludmila , Shamtieva Kamila , Dobrynina Larisa
Published: October 2018

Introduction:
Cervical artery dissection (CeAD) is the most frequent cause of ischemic stroke in young adults. It is suggested that connective tissue dysplasia (CTD) underlies in the arterial wall weakness predisposing to dissection.
The aim
: to elucidate CTD signs that have prognostic and diagnostic significance for CeAD.

Methods:
We examined 80 patients (mean age 38,5±13,5; 49 females, 61,2%) with CeAD, verified by MRI/MRA and 20 healthy volunteers (mean age 30,3±6,7; 12 females 60%). We assessed 48 signs selected from criteria of the vascular type of Ehlers-Danlos syndrome, Marfan syndrome, Beighton criteria of joint hypermobility and other. In addition we estimated arterial hypotension (≤100/70 mm Hg), and headache in the past history. Each sign was counted as present or absent, resulting in an individual CTD score. On the basis of linear regression analysis these signs were divided into major and minor signs.

Results:
CTD signs were found more frequently in CeAD patients than in the control (mean score 7,9 ± 3,6 vs 4,6 ± 2,5; p<0.0039). The following CTD signs were significantly more often in patients than in control: arterial hypotension (51% vs 20%, Р=0,018), extensive bruising (40% vs 10%, Р=0,016), widened atrophic scars (23% vs 0%, Р=0,02), headache in the past history (60% vs 35%, p=0,027) - major signs; translucent skin (29% vs 5%, Р=0,037), hight palate (20% vs 0%, Р=0,037), nasal bleeding (34% vs 15%, Р=0,044), blue sclera (20% vs 5%, Р=0,05), propensity to constipation (30% vs 0%, Р=0,05) - minor signs. If there were 4 major and 2 small signs logistic regression model gave 75% predictive value of dissection. The reliability of these signs was confirmed by ROC analysis (AUC 0,90 [95% CI 0,84-0,96], sensitivity - 86%, specificity - 85%).

Conclusion:
CTD signs are highly prevalent in patients with CeAD that is in accordance with our morphological data that arterial wall dysplasia is a main cause of spontaneous dissection. The presence of 4 major and 2 minor signs may be used to estimate the predisposition to CeAD and in some cases as additional argument at clinical diagnosis.
Abstract WP220: Onset to Needle Times Differ in Patients with Varying Stroke Severity: A Retrospective Review of a National Stroke Audit
Authors: Lau Lina , Turner Melanie , Barber Mark , Langhorne Peter , Dennis Martin , MacLeod Mary J ,   Scottish Stroke Care Audit
Published: October 2018

Introduction:
Outcomes following stroke thrombolysis have been observed to be largely dependent on time to treatment. Patients with more severe strokes have more obvious symptoms and are easily diagnosed while patients with milder strokes are often in a grey area where misdiagnosis (particularly as resolving TIA) is common, therefore leading to delayed thrombolysis. Time to treatments are not only influenced by in-hospital factors, but pre-hospital factors as well. Delaying treatment in minor stroke patients might have detrimental effects and diminish chances of good outcome. We wished to examine the effects of stroke severity on onset to needle times (OTN) and door to needle times (DTN) using a national stroke data set.

Methods:
A retrospective analysis was done on patients who were eligible for and treated with recombinant tissue-type plasminogen activator (rt-PA). Data for all patients in Scotland treated with alteplase between 2010 and 2013 was available from the Scottish Stroke Care Audit (SSCA). Components of the thrombolysis service delivery pathway was compared between minor (NIHSS score of ≤5) and more severe stroke (NIHSS score of ≥6) patients.

Results:
OTNs and DTNs are both negatively correlated to pre-treatment NIH scores. However, OTN shows greater correlation to pre-treatment NIH scores (r=-0.212 p<001) than did DTN (r=-0.057, p=0.021). Minor stroke patients have longer onset to admission times (105.5 vs. 83 minutes; p<0.001), OTNs (180 vs. 160 minutes; p<0.001), admission to scan times (37 vs. 31 minutes; p=0.004), and were younger (71.22 vs. 74.18 years; p<0.001).

Conclusion:
This study confirms evidence that minor stroke patients are experiencing delayed thrombolysis, which could reduce the opportunity for benefit for stroke survivors. The reasons for this delay appear to include pre-hospital stroke recognition and response, and also in-hospital patient/clinician decision making as the risks and benefits may be viewed differently in milder strokes. Stroke care guidelines could consider using OTNs as a stroke care standard instead of DTNs in future reviews of management standards.
Abstract WP231: Documentation of Last Known Well Time in the Michigan Stroke Coverdell Registry
Authors: Demel Stacie L , Nickles Adrienne V , O’Brien Suzanne , Ibrahim Ghada , Szabo Zsuzsanna , Quartermus Krystal , Kinnucan Sherry , Wahl Robert , Scorcia-Wilson Teri , Reeves Mathew J
Published: October 2018

Background:
Last known well (LKW) time is critical information when determining eligibility for acute stroke treatments, but is often unknown or not documented. Our aim was to use the Michigan Stroke Coverdell Registry to identify independent predictors of missing LKW and the association between missingness and outcomes.

Methods:
Forty hospitals contributed data to the registry between 2008-2017. Patients were excluded from the analysis if they had an in-hospital stroke or arrived via transfer from another healthcare facility. Independent factors associated with missing LKW time documentation were identified using multivariable logistic regression.

Results:
Out of total of 51,066, LKW was missing in 24,675 (48.3%) of the cases. Characteristics of cases and their association with LKW missingness are shown in the Table. Missing LKW documentation was higher among non-Caucasians, those with an onset in a health care facility (versus home), those who arrived via private vehicle (vs EMS), those with hemorrhagic strokes and those who presented with aphasia or weakness. Documentation of LKW was lower in those who presented with TIA or had a history of atrial fibrillation or prior TIA. LKW missingness varied widely between hospitals (Range: 10.3 - 72.5%) (Figure). Patients without documentation of LKW had longer lengths of stay, higher in-hospital mortality, and were more likely to have missing NIHSS data (63% versus 37% for those with documented LKW).

Conclusions:
Documentation of LKW time is common, varies substantially between hospitals and is associated with poor outcomes. These data provide an opportunity for education and quality improvement efforts to improve documentation.
Abstract WP243: Use of Wearable Technology in Remote Evaluation of Acute Stroke Patients: Feasibility and Reliability of Xpert Eye™: A Google Glass Based Solution
Authors: Noorian Ali Reza , Bahr Hosseini Mersedeh , Avilda Gilda , Gerardi Richard , Andrle Anne-Fleur , Su Michael , Starkman Sidney , Saver Jeffrey L , Sharma Latisha K
Published: October 2018

Background:
Tele-stroke has been an efficient cost-effective way to standardize care and improve access to immediate neurologic care for rural hospitals and other areas underserved by neurologists. Virtual telestroke support is commonly used in the Emergency Department. Hands-free wearable technology allows for seamless communication and faster more informed decisions. It can advance the triage of stroke patients into the pre-hospital setting at the scene or in the ambulance and facilitate the routing of patients to comprehensive stroke centers.

Objective:
To assess the feasibility and reliability of Xpert Eye
TM
solution, a Google Glass- based wearable solution in evaluating patients with suspected acute stroke.

Methods:
Consecutive patients with suspected stroke were evaluated concurrently by an on-site neurologist wearing Xpert Eye
TM
solution and a remotely located neurologist through Xpert Eye
TM
platform. Inter-rater reliability in calculating the NIH Stroke Scale (NIHSS) scores was evaluated.

Results:
Seventeen patients were included. There was a high degree of correlation in total NIHSS score (ICC 0.99 and weighted kappa 0.88) and across all NIHSS sub-items (ICC 0.81-1 and weighted kappa 0.68-1) between the two examiners. The maximum difference between the two NIHSS scores was 3.

Conclusion:
The use of Xpert Eye
TM
solution in tele-stroke is feasible and reliable. Using wearable solutions in tele-stroke can advance the care faster to the pre-hospital setting, at the scene or in the ambulance and can potentially facilitate triaging patients to appropriate stroke centers in the community.
Abstract WP250: Evaluating & Optimizing the Model of Thrombotic MCAO in Mice
Authors: Zhang Rongrong , Zhang Wenting , Stetler Ruth A , Hu Xiaoming , Chen Jun , Gao Yanqin
Published: October 2018

Background:
The embolic model of middle cerebral artery occlusion (MCAO) by thrombus mimics the ischemic stroke in human and is amenable to thrombolytic therapies with recombinant tissue plasminogen activator. However, this model has not been thoroughly investigated and standardized. The present study was performed to optimize this model in mice.

Methods:
Male C57BL/6 mice (8-10 week old) were subjected to MCAO induced by autologous or allogeneic thrombus measuring 5, 10, or 15 mm in length. Blood was placed in a tube (20μm diameter) with thrombin before injecting with sterile saline into internal carotid artery (ICA). Cerebral blood flow (CBF) was monitored by laser-Doppler or laser speckle before MCAO. Infarct was assessed by TTC staining 24 hours after MCAO. Neurological deficits were evaluated by modified neurological severity score (mNSS), rotarod test and corner test 1-7 days after ischemia.

Results:
Thrombus injection resulted in an abrupt drop of CBF to less than 30% of baseline in the MCA territory. The areas with more than 50% CBF decrease at 3 h after thrombus injection was significantly correlated to infarct volume at 24 h after MCAO (r=0.792, P=0.019, Pearson′s correlation analysis), suggesting that continuous decrease in CBF within 3 h can predict brain damage after stroke. No significant differences in infarct volume between autologous and allogeneic thrombus were observed (25.31±6.45 mm
3
vs 23.00±6.31 mm
3
, p>0.05). Allogeneic thrombi of 10 mm and 15 mm lengths caused reproducible infarct with detectable neurological deficits in mice. The 10 mm thrombus was chosen as the optimal thrombus length as it caused similar morphological and functional alterations compared with 60 min suture model of MCAO. In contrast, 15 mm thrombus resulted in significantly larger infract volume, worse sensorimotor functions and higher mortality in mice.

Conclusion:
Embolic MCAO did not yield stable CBF reduction compared to the classical suture MCAO. However, continuous decrease in CBF in the embolic model for at least 3 h resulted in successful infarct induction. The 10 mm autologous thrombus is suitable to induce reproducible infarct with neurological deficits in adult mice.
Abstract WP251: Neuroprotective Effect of a New Endovascular Hypothermia: Intrajugular Cooling Infusion in Experimental Ischemic Stroke
Authors: Duan Yunxia , Ding Yuchuan , Wu Di , Mitchell Huber , Shi Jingfei , Ji Xunming
Published: October 2018

Introduction:
Induction of cerebral hypothermia is a well-known therapy for ischemic stroke. However, its use is highly limited by the technical requirements. Intrajugular (IJ) cannula placement is a frequently conducted procedure in the Emergency Room. The purpose of this study was to determine the neuroprotective efficacy of IJ cold saline infusion compared to intracarotid (IC) infusion by microcatheter.

Methods:
Middle cerebral artery (MCA) occlusion (2 h) was achieved by an intraluminal filament in rats. Rats were randomized to 4 groups (n=56 total): sham surgery, stroke only, stroke with IC or IJ. In IC and IJ, 6 ml of isotonic 0°C saline was perfused into the right common carotid artery or internal jugular vein for over 30 minutes. The temperature of rectum, cortex and striatum was recorded for 100 min. The extent of brain injury was determined by infarct volume and neurological deficit. The BBB damage was assessed by the leakage of Evans Blue and brain edema .Expressions of apoptotic proteins (Bcl-2, Caspase-3), as well as BBB function associated molecules, including matrix metalloproteinase (MMP)-9 and aquaporin (AQP)-4 were evaluated by Western blotting.

Results:
The temperature of rectum, cortex, and striatum from the control group remained normal. Both IC and IJ induced a rapid drop of temperature, especially in the cortex and striatum with the lowest temperature of 34.5±0.9°C/33.5±0.8°C, or 34.6±0.7°C/33.5±0.9°C, respectively, at 40 minutes later. Both IC(35.05±0.05%) and IJ (35.56±0.07%)reduced infarct volumes compared to the control (48.08±0.04%).The neurological deficits were reduced by both IC and IJ treatment. IC reduced brain edema by 61%, while IJ by 52%. IC and IJ both significantly reduced the Evans Blue leakage as compared to control (1.04 ug/g and1.05 ug/g vs.1.11ug/g). Increased Bcl-2 and decreased caspase-3 were found in IC and IJ groups. MMP-9 and AQP-4 were also reduced by IC and IJ cooling perfusion.

Conclusion:
As compared to IC, IJ exerted a similar hypothermia and neuroprotection against ischemic stroke. Both IC and IJ reduced edema. Due to easy access to IJ injection, brain cooling by IJ could be developed as a promising hypothermia therapy due to its safe, quick, and effective features.
Abstract WP254: Inhibition of Calcium/Calmodulin-Dependent Protein Kinase Kinase (CaMKK) Exacerbates Endothelial Cell Impairment After Cerebral Ischemia
Authors: Sun Ping , Liu Lin , Koellhoffer Edward , McCullough Louise , Li Jun
Published: October 2018

CaMKK (α and β) is a major kinase activated by elevated intracellular calcium. We have previously demonstrated CaMKK is neuroprotective in stroke. Pharmacological inhibition of CaMKK exacerbated outcome while overexpression reduced brain injury in mice. Brain microvascular endothelial cells play an essential role in maintaining BBB integrity, disruption of which aggravates ischemic injury. Interestingly, CaMKK activates a key endothelial protectant Sirtuin1 (SIRT1), although this interaction has never been studied in stroke. We hypothesized that CaMKK protects brain endothelial cells (EC) through activation of SIRT1 after ischemia. Oxygen-glucose deprivation (OGD, 18 hours) with reoxygenation (24 hours) was performed in human brain microvascular endothelial cells (HBEC-5i). Cell viability was assessed using a CCK-8 assay. Middle cerebral artery occlusion (MCAO, 90 mins) was used to induce stroke in male mice (20 to 25 g). The CaMKK inhibitor STO-609, SIRT 1 inhibitor EX-527, or CaMKK β siRNA was added to EC before OGD. Data are presented as mean±SEM. STO-609 treatment reduced cell viability (%) after OGD (vehicle 71.45 ± 5.60 vs. STO-609 55.06 ± 5.02, n=4, p<0.05). Knockdown of CaMKK β using siRNA increased cell death following OGD. Mechanistically, inhibition of CaMKK by STO-609 led to significant down-regulation of phosphorated SIRT1 (Ser-27) after OGD. Levels of total SIRT1 were also reduced by STO-609, consistent with the notion that phosphorylation prevents the degradation of this protein. Changes in downstream targets (e.g., eNOS) of SIRT1 were accordingly observed with STO-609 treatment. Further, the effect of STO-609 on cell viability after OGD was absent when SIRT1 was concurrently inhibited by EX-527 (STO-609+EX-527 45.19 ± 2.09 vs. EX-527 44.42 ± 2.89, n=4, p>0.05). Finally, in a MCAO model, intracerebroventricular injection of STO-609 (pre-stroke) significantly worsened BBB integrity (Evans blue assay) after 24-hour reperfusion (MCAO+DMSO 17.83 ± 6.34 versus MCAO+STO-609 55.74 ± 8.88, n=5/6;
P
<0.05). In conclusion, we demonstrate that CaMKK inhibition reduces EC viability after ischemia via SIRT 1. Our data suggest CaMKK attenuates ischemic brain injury by protecting the microvascular system and preserving BBB integrity.
Abstract WP256: Paradoxical Neuronal Survival Against Cerebral Ischemia in Lactate Dehydrogenase B Knock-out Mice via Vascular Adaptation
Authors: Lee Jin Soo , Han Song Mi , Yoon Bok Seon , Son Keoung Sun , Lee Seong-Joon , Hong Ji Man , Park Chan Bae
Published: October 2018

Background:
Among several routes of neuronal energy source, astrocyte-neuron lactate shuttle is known to be the main pathway in brain. After lactate is formed in astrocytes, it is transferred into neurons via monocarboxyl transportase. In neurons, lactate is transformed into pyruvate mainly by lactate dehydrogenase (LDH) 1, which consists of 4 units of LDH B (LDHB). To evaluate the effects of lactate shuttle pathway alteration on cerebral ischemia, we developed LDHB knock-out (KO) mouse. We hypothesized that ischemic neuronal damage would be more severe in LDHB KO mice compared with wild-type (WT) mice.

Methods:
LDHB KO and WT mice (age, 12-14 weeks) were used for this study. Bilateral common carotid arteries were transiently occluded for 10 minutes, and mice were sacrificed after 3 days. Cresyl violet staining was performed for histological analysis. Immunohistochemistry was performed for GFAP, Iba-1, TUNEL, etc. For evaluation of vascular collateral status, diameters of basilar artery posterior communicating artery, and the ratio of posterior communicating artery diameter to basilar artery was measured.

Results:
Contrary to our hypothesis, the ischemic damage was less pronounced in the LDHB KO mice compared to WT mice. The number of surviving neurons in the hippocampal CA 1 region was significantly higher in LDHB KO than in WT. The number of activated astrocytes in the hippocampus was also significantly higher in LDHB KO than in WT. The number of microglia in the hippocampus, however, was significantly lower in LDHB KO group than in WT group. TUNEL-stained neuronal cells in the hippocampus was significantly less in LDHB KO group than in WT group. In analysis of vascular collateral status, the diameter of the basilar artery did not differ; however, the ratio of the posterior communicating artery to basilar artery was significantly higher in LDHB KO group than in WT group. The ratio did not differ in LDHB KO and WT mice without cerebral ischemia.

Conclusions:
The brain of LDHB KO mice appeared to be more resistant to ischemic insults compared to WT mice. The mechanism of ischemic resistance in LDHB KO mice is thought to result from better vascular response for collateral supplies. Further analyses to prove the mechanism of ischemic resistance are warranted.
Abstract WP260: Uric Acid Reduces Infarct and Improves Neurological Function in Female Mice One Week After Transient Cerebral Ischemia
Authors: Dhanesha Nirav , Cintron-Perez Coral J , Thedens Daniel , Kort Alexa J , Chuong Vicky , Rivera-Dompenciel Adriana M , Chauhan Anil , Leira Enrique C , Pieper Andrew A
Published: October 2018

Background & Purpose:
Exogenous administration of uric acid, a naturally occurring antioxidant that scavenges reactive oxygen species in vasculature, has shown protective efficacy in both rodent models of stroke and in human stroke patients in Spain as an adjuvant treatment to mechanical thrombectomy. In accordance with STAIR-RIGOR criteria, confirmation of efficacy in alternative preclinical models is required before clinical trials can be initiated in the United States. To date, preclinical efficacy has only been established in the acute setting in male rodents.

Methods:
Seven to nine week old ovariectomized female mice were subjected to filament-induced right middle cerebral artery ischemia and reperfusion, an established preclinical model of mechanical thrombectomy. Fidelity of the procedure was monitored by laser Doppler flowmetry in all animals. A separate lab randomly assigned animals to vehicle vs uric acid infusion, which was initiated immediately after 45 minutes of reperfusion. Post-stroke analysis of infarction size and neurological function were conducted by investigators blind to treatment group, with a 7 day primary endpoint and intermediary analysis at 1and 3 days.

Results:
Infarct size and neurological function at 7 days post-stroke was significantly improved in uric acid-treated animals, relative to vehicle.

Conclusions:
Efficacy of uric acid in preclinical models of stroke is now expanded to include female mice analyzed at a more chronic time point than has been investigated previously. These results supports STAIR-RIGOR driven determination of the suitability of acute administration of uric acid as an adjuvant to mechanical thrombectomy in clinical trials for patients with stroke.