bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP368: Effectiveness and Safety of Luseogliflozin, Sodium-Glucose Cotransporter2 Inhibitor, to Treat Hyperglycemia in an Acute Stroke Stage
Authors: Mori Takahisa , Tanno Yuhei , Kasakura Shigen , Yoshioka Kazuhiro , Nakai Noriyoshi
Published: October 2018

Introduction:
Hyperglycemia found at arrival or after admission must be treated as soon as possible in acute stroke patients, because hyperglycemia impairs their clinical outcome. However, it hasn’t been established how to treat it.

Hypothesis:
Sodium-glucose cotransporter-2 (SGLT2) inhibitors can lower blood glucose level soon and safely in an acute stroke stage.

Patients and Methods:
We included acute stroke patients 1) who were admitted between September 2015 and June 2017, 2) who could orally take food after admission, 3) who presented fasting blood glucose level of higher than 150 mg/dl on the 3rd day, and 4) who received the SGLT2 inhibitor of luseogliflozin 2.5mg on the 3rd day to lower blood glucose level. We excluded patients undergoing enteral feeding or insulin therapy. We didn’t use sulfonylureas nor glinides. We provided food with appropriate calorie, determined according to Harris-Benedict equation, including carbohydrates (carbo) adjusted to 40% of the target calorie. We evaluated blood glucose level, urine glucose and urine ketones at arrival and on the 6th day.

Results:
Fifty-six patients matched our criteria. On admission, their average age was 71 years, average body mass index was 24.1 kg/m2, their average HbA1c was 7.6 %, blood glucose level was 192 mg/dl and creatinine clearance was 64.6 ml/min. Patients take food with average 1400 kcal including carbo of 140 g/day. Average three days after starting luseogliflozin treatment, their average fasting blood glucose level was improved to 117 mg/dl, 54 patients (96%) presented positive urine glucose and 29 patients (52%) positive urine ketones. No symptoms of hypoglycemia or ketoacidosis occurred.

Conclusion:
Luseogliflozin coupled with food including carbo of average 140 g/day could lower blood glucose level soon and safely in acute stroke patients with appropriate conditions.
Abstract TP370: Performance of a New “Code Stroke” Process in Hospitalized Patients in a Comprehensive Stroke Center in Minnesota
Authors: Droegemueller Carol J , Wagner Roberta L , Kashyap Bhavani , Clayton Mitchell W , Fennig Mary W , Hanson Leah R , Hussein Haitham M
Published: October 2018

Background and Purpose:
Literature suggests that recognition and management of stroke of hospitalized patients is difficult, and the morbidity and mortality rates of in-patient strokes exceed those of out of hospital stroke. Timely treatment is an important factor for a favorable prognosis for hospitalized patients suspected of having a stroke. A new protocol for in-patient stroke was implemented as a quality improvement project at our comprehensive stroke center starting January 2017.

Methods:
The new protocol included focused nursing education, replacement of 2-step activation process with 1-step process whereby the bedside nurse activates ‘Code Stroke’ using same criteria as used by EMS and ED triage nurses. Code Stroke activates a specialized stroke team (neurologist, ICU physicians, ICU nurses, pharmacy) and clears the CT scanner. Accurate documentation was encouraged and template notes were provided. Expectations were put forth regarding the relevant quality metrics. Feedback was provided in real-time as well as in writing, to participating care team. This analysis was done utilizing data from a prospectively maintained database of inpatient stroke, feedback communications, and chart review. The following metrics were used to examine the performance of the new process: rate of stroke symptoms identification, errors in paging, errors in documentation, time to CT, and outcome of code activation.

Results:
In the 6 months prior to the new protocol, a ‘Code Stroke’ was activated 5 times, only one was a true stroke and was treated with thrombectomy. In the 6 months after the new protocol, ‘Code Stroke’ was activated 46 times, with 15 confirmed strokes (14 ischemic, 1 hemorrhagic). A change in care occurred for 13 patients, including IV alteplase (n=2), thrombectomy (n=1), change in medical management (n=9), and decompressive hemicraniectomy (n=1). Mean time for Code Stroke to CT was 26 minutes despite errors in pages (wrong call back number, incorrect code designation).

Conclusion:
Our new process increases detection and treatment of in-patient strokes. Elements of success include system-wide organization, simplifying the process, mirroring ED process, and availability of stroke response team.
Abstract TP375: Strength in Numbers: Enhancing Bedside Shift Report with an Advanced Registered Nurse Practitioner
Authors: West Noella C , Pitak Denyse
Published: October 2018

Background and Purpose:
According to research, bedside shift report has a direct correlation with improved nursing communication, patient satisfaction, patient safety and quality of care. Exploring the addition of an advanced practice provider, this innovative quality improvement initiative was implemented on a 47 bed neuroscience unit at a trauma level one hospital. Stroke related patients were targeted with cognitive functioning in mind. The purpose of this evidence based nursing practice and quality enhancement initiative was to improve the patient satisfaction, experience and outcomes as well as improving nursing communication by the involvement of an advanced nurse practitioner.

Methods:
The reengineered plan of care was implemented by incorporating an advanced nurse practitioner to bedside shift report. Stroke patients where the nurse practitioner was the primary provider joined the nurse to nurse communication team during bedside shift report to improve quality measures.

Results:
This interdisciplinary initiative contributed to a steady increase in patient’s ratings of communication with nurses and advanced practice providers. There was also some increase in patients’ better understanding of their plan of care which encouraged participation with active decision making. As a result, nursing staff communication improved and satisfaction as well as enhanced professional relationships among providers and nurses was demonstrated.

Conclusions:
Reengineering of the interdisciplinary team approach incorporating an advanced practice provider with bedside shift report increased patient satisfaction, patient experience, improved nursing communication and overall improvement of professional relationships. This quality enhancement initiative was vital in increasing patient satisfaction, expediting the plan of care, providing betterdecreasing length of stay and quality of care and a collegial relationship with nurses in the stroke population.
Abstract TP377: Stroke Navigator Program Supports Community Reintegration and Decreases Readmissions
Authors: Juntura Anh , Jett Glen , Cudlip Fern , O’Donnell Christine
Published: October 2018

Background:
Navigating the healthcare system is complex. We believe successful community reintegration for stroke patients requires: 1) overcoming barriers; 2) educating on disease process, risks, medications, and when to seek medical attention; 3) integrating patient support; 4) promoting rehabilitation; and 5) coordinating follow-up care.

Purpose:
We sought to establish the impact value of a Stroke Navigator Program (SNP) in supporting the transition from acute care through community reintegration. Measures utilized to demonstrate program efficacy included patient recall of key information, adherence to medications and appointments, and incidence of hospital readmission.

Methods:
SNP patients were enrolled during initial hospitalization. An assessment was performed to determine baseline knowledge in stroke etiology, symptoms, and medication use; support structures; individual goals; and readmission risk. Follow-up contacts for further assessment and evaluation of patient progress were conducted. These included access to rehabilitation services and completion of medical follow-up appointments. Contacts were planned, managed and documented using workflow management software.

Results:
Between January 1, 2015 and December 31, 2016, 463 patients were enrolled. Interviews were completed with patients, spouses or significant others, family members or caregivers, and others at specific intervals after hospital discharge. A majority of respondents verbalized basic understanding of the stroke diagnosis, with similar results reported in the ability to obtain medications and with medication adherence. Assessment of initial, post-discharge comprehension demonstrated inconsistent recall of specific stroke symptoms, individual risk factors, and when to seek emergency medical assistance. The 30-day, all-cause hospital readmission rate for enrolled patients was 2.6%, compared to an overall stroke patient readmission rate of 6.3% for the period.

Conclusion:
Participation in the SNP correlated with fewer hospital readmissions while reinforcing and validating patient knowledge in areas that can impede successful community reintegration.
Abstract TP378: How Caregivers Potentially Prevent Hospital Readmissions
Authors: Pierce Linda L , Steiner Victoria
Published: October 2018

Background:
Since the Patient Protection and Affordable Care Act law of 2010, hospitals are held accountable by payers for readmissions. Family caregiving is an essential, yet understudied, factor that can hasten, delay, or prevent hospital readmissions. The purpose of this study was to describe what actions family caregivers of persons with stroke take to prevent readmissions, and if actions are taken, the reasons for those actions.

Methods:
Guided by Friedemann’s framework, this study used a qualitative descriptive design. A one-time structured interview was conducted to explore actions taken by family caregivers to prevent hospital readmissions for care recipients with stroke, and reasons for these actions. Participants were adult family caregivers from one Ohio city who had been providing care for at least six months after initial hospitalization. Data were analyzed using Colaizzi’s content analysis and Friedemann’s framework was applied to the emerging themes.

Results:
Caregivers (n=13) indicated actions that encompassed five themes: 1) Enhancing physical health with day-to-day interventions (system maintenance and individuation in Friedemann’s terms), 2) Providing mental and emotional support within the dyad (coherence), 3) Pursuing healthy relationships with others through community involvement (coherence), 4) Utilizing services within the healthcare system (system maintenance), 5) Thinking ahead and making the environment safe (system maintenance and individuation). Reasons underlying caregiver actions were related to four themes: 1) Fearing other health problems will occur if no action is taken (system maintenance), 2) Believing actions will improve or prevent health problems (individuation and system maintenance), 3) Adjusting to challenges based on past experiences (individuation and system change), 4) Recognizing a history together and a commitment to each other (coherence and system maintenance).

Conclusion:
Understanding actions stroke family caregivers take, and the underlying reasons for those actions, enables healthcare providers to deliver targeted education and suggest community resources to potentially prevent hospital readmissions.
Abstract TP381: Health-related quality of life in stroke survivors: The 2015 Korea National Health and Nutrition Examination Survey
Authors: Shin Cha-Nam , Sim Jeongha , Ahn Dongchoon
Published: October 2018

Introduction:
Health-related quality of life (HRQOL) is an important index of poststroke health outcome.

Hypothesis:
We hypothesized that the HRQOL in stroke survivors than individuals without stroke would be worse and associated with sociodemographic status, impaired health behaviors, and comorbidities among stroke survivors in Korea.

Methods:
This cross-sectional, population-based study included 5130 (132 stroke survivors; 4998 individuals without stroke) Korean adults (aged ≥18 years) who had complete data on stroke-related items in the 2015 Korea National Health and Nutrition Examination Survey. Descriptive statistics, χ
2
test, t-test, and regression analyses were used.

Results:
Stroke survivors than adults without stroke were more likely to be older, had lower income and education level, while having more physician-diagnosed diseases (hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, angina, arthritis, osteoporosis, and depression), less meeting aerobic exercise guidelines with more physical activity limit, and more smoking at present or past (p<.001). EQ-5D index and all 5 dimensions of EQ-5D (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) of stroke survivors were much worse than that of adults without stroke (p<.01). Stroke survivors who had lower income and education level, did not meet the aerobic exercise guidelines with more physical activity limit, and had comorbidities (diabetes mellitus, depression) were more likely to have worse HRQOL score (p<.01). Education level, physical activity limit, and depression were predictors of HRQOL in stroke survivors (p<.05).

Conclusions:
Clinicians should pay a special attention to stroke survivors with lower sociodemographic status, while improving HRQOL of stroke survivors by intervening physical activity and comorbidities, which is important in planning effective poststroke care.
Abstract TP383: Younger Caregivers of Stroke Survivors Experience Personal Growth through Caregiving
Authors: Mathews Maureen , Liu Tiffany , Beck Judith , Connell Diana , Couri Candace , Jahnel Jan , McNeil Clayton , Machens Nancy , Nair Deepak , Nunley Marylee , Schaer Larry , Upadhyaya Manas , Wang David
Published: October 2018

Title:
Younger Care Givers of Stroke Survivors Experience Personal Growth through Caregiving

Background:
Stroke is the leading cause of disability in the US. One in four patients with stroke is disabled. Providing care to these survivors long term is very burdensome to the family. Wellbeing and respite of care givers (CG) has not been studied well in the past. In this study, we focused on quality of life (QOL) of the young care giver (YCG) of stroke survivors. The Retreat and Refresh Stroke Camp (RRSC), initiated in 2004, offers respite, opportunities to develop new relationships, networking, sharing and education/access to resources.

Methods:
QOL of CG attending the Retreat and Refresh Stroke Camp (RRSC) in 2016 -2017 was assessed using the Adult Carer Quality of Life Questionnaire (ACQOLQ). YCG were defined as 65 years and younger. The ACQOLQ addresses 8 subcategories of QOL. High (11+) subcategory score indicates high QOL in that category, a score (0-5) indicates low QOL and potential difficulties. Emails were sent to all CG with a link to ACQOLQ in Survey Monkey. Results were analyzed using descriptive statistics and unpaired t-test.

Results:
Seventy four CG responded to the survey. Sixty one percent are YCG (mean 61.2 years), 86.49% female. Approximately 40% YCG provided care >70 hours/week. Mean duration of caring 6.36 years. Mean ACQOLQ score 69.23, indicating mid-range QOL. Seven had a high QOL, 4 had low QOL. Of the eight subcategories, support for caring averaged 7.17; caring choice, 7.43; caring stress, 8.52; money matters, 7.96; personal growth, 8.46; sense of value, 9.61; ability to care, 10.41; and care satisfaction, 9.66. Unpaired t-test, showed higher QOL in personal growth (P<0.05) and more financial concerns (P<0.05) for these YCG.

Conclusions:
The ACQOLQ provides a benchmark for QOL assessment for the RRSC CG. RRSC may have played a role in improving the self-worth, confidence, feelings of appreciation of CG. RRSC must reach out to populations of higher stroke incidence and families of stroke survivors. Camp Directors will use this information to develop strategies to improve CG freedom, money management, and general support.
Abstract TP386: Growing Intracranial Aneurysms in Older Patients Tend to Have Higher Annual Growth Rates
Authors: Chang Dennis , Yokota Hajime , Morimoto Emiko , Chang Warren , Szeder Viktor , Villablanca Pablo , Duckwiler Gary , Chien Aichi
Published: October 2018

Introduction:
Numerous previous studies have discussed the correlation between patient age and aneurysm rupture. However, the existing base of knowledge regarding the relationship between patient age and aneurysm growth, specifically growth rate, is significantly smaller. The objective of this study is to examine the correlation between patient age and aneurysm growth in order to help devise better clinical management strategies.

Hypothesis:
Growing aneurysms in older patients will exhibit a higher mean growth rate relative to those in younger patients.

Methods:
In this study, the records of 361 patients between the age of 40 and 97 at the time of initial diagnosis with unruptured intracranial aneurysms in the UCLA Medical Center between January 2005 and December 2015 were reviewed. These patients were continuously followed using CTA neurovascular imaging, ending when the patient either received surgical or endovascular treatment or discontinued follow-up visits.

Results:
A total of 496 UIA in the 361 patients were classified into four groups by patient age (40-49, n=56; 50-59, n=120; 60-69, n=145; 70+, n=175). Incidence of growth was 14.29%, 11.67%, 8.28%, and 12.57% for the 40-49, 50-59, 60-69, and 70+ groups, respectively. Growth rates were 0.30±0.12, 0.58±0.42, 0.90±0.72, and 0.78±0.75 mm/yr for the 40-49, 50-59, 60-69, and 70+ groups, respectively. Differences in growth rates were not significant between the four groups (ANOVA, p=0.15). However, when patients were divided by age 50 years, growth rates were significantly higher in the 50+ group (p<0.05).

Conclusion:
Although there was a high level of variation in growth rate between individual cases, this study found that patients with growing aneurysms over the age of 50 are at a higher risk for rapid aneurysm growth compared to younger patients, a finding that may prove helpful in developing clinical management protocols.
Abstract TP391: Reach Out: An Exploratory Randomized Clinical Trial of Emergency Department-Based Hypertension Management
Authors: Meurer William J , Brown Devin , Skolarus Lesli
Published: October 2018

Introduction:
Hypertension (HTN) is the most important modifiable stroke risk factor. The Emergency Department (ED) represents an opportunity to identify and treat HTN in difficult-to-reach populations. Electronic health records (EHR) can alert clinicians and researchers when parameters, such as elevated blood pressure (BP) are met. Our primary objective was to determine what proportion of ED patients would utilize prompted BP self-monitoring and respond to texts with home readings consistent with persistent HTN.

Methods:
This was a randomized, controlled trial of patients recruited from a university ED with a volume of about 70,000 adult patient visits per year. Real-time EHR alerts identified patients with systolic BP ≥160 or a diastolic BP ≥100 (stage II HTN) who were likely to be discharged from the ED. At enrollment, all subjects were provided a home BP cuff and were sent weekly text messages to check their BP and text back the values to the study team. Subjects responding to texts and indicating persistent HTN during the 3-week run-in period were randomized to control or a 12-week intervention consisting of healthy behavior text messages and reminders to check BP and text the result back to investigators. We conducted secondary analyses evaluating change in BP over 12 weeks based on the self-reported assessments.

Results:
Over 9,300 patients with elevated BP were identified through the EHR alerts over 7 months; data were abstracted on 1,908 patients. Of these, 169 were approached and 104 patients enrolled (64%). Of those enrolled, 73 (70%) texted back at least 1 BP reading during the run-in period of which 55 (53% of the 104) subjects had persistent HTN; this was higher than pre-specified goal of 25.5%. In those randomized (n=55), SBP decreased 8.9 mm Hg in the intervention group compared to an increase of 8.3 mm Hg in controls (p=0.039, see table).

Conclusion:
Real-time, ED EHR based patient selection combined with mobile health monitoring of BP is feasible and promising.
Abstract TP392: Evaluation of the CHADS
2
, CHA
2
DS
2
-VASc, and R
2
CHADS
2
Risk Assessment Scores in Continuous Flow LVADs
Authors: Lamba Harveen , Santiago Adriana , Hyak Jonathan , Kim Mary , Alnajar Ahmed , Kawabori Masashi , Sugira Tadahisa , Kurihara Chitaru , Civitello Andrew , Ono Masahiro , Loor Gabriel , Frazier O.H. , Cheema Faisal H , Morgan Jeffrey
Published: October 2018

Background:
The development of stroke while on continuous flow left ventricular assist device (CF-LVAD) remains a source of significant morbidity and mortality. The ability to risk stratify these patients can improve postoperative management.

Objective:
To describe the overall experience of cerebrovascular accidents in CF-LVAD patients at a large volume tertiary center and compare the utility of CHADS
2
, CHA
2
DS
2
-VASc, and R
2
CHADS
2
scores.

Methods:
A retrospective analysis of 522 patients (524 CF-LVADs: HeartMate-II=402; Heartware=122), between 2003 and 2016, was conducted. Post-operative heparin for 2-3 days, warfarin (goal INR 2-3), and 80-325mg aspirin were administered daily. Cerebrovascular vascular accident (CVA) was defined as any focal or global deficit with positive imaging. The CHADS
2
, R
2
CHADS
2
and CHA
2
DS
2
-VASc scores were calculated. Baseline characteristics and risk assessment scores were compared between patients with ischemic CVA (ICVA) and no CVA (nCVA). Kaplan-Meier analysis was conducted.

Results:
Mean age was 54.7±13.6 years, 21.8% were female and 44.8% had ischemic cardiomyopathy. Eighty patients (15.3%) had 98 events of ICVA. Median duration between implant and ICVA was 127 [range 1-2226] days. Hemorrhagic conversion occurred in 9 (9.2%) patients. The CHADS
2
(ICVA=2.4±1.0, nCVA=2.3±1.1, p-value=0.53), CHA
2
DS
2
-VASc (ICVA=3.2±1.3, nCVA=2.9±1.3, p-value=0.08) and R
2
CHADS
2
(ICVA=3.5±1.5, nCVA=3.2±1.6, p-value=0.22) were all higher for ICVA cohort. Patients with multiple ICVAs had a mean CHADS
2
score of 2.5±0.74, CHA
2
DS
2
-VASc score of 3.5±1.1, and R
2
CHADS
2
score of 4±1.2. Freedom from stroke was significantly lower in the CHA
2
DS
2
-VASc ≥3 compared to the CHA
2
DS
2
-VASc <3 [Figure: Kaplan-Meier log-rank p-value=0.009].

Conclusion:
CHA
2
DS
2
-VASc of ≥3 was associated with ICVA in this cohort of CF-LVAD patients. Specifically tailored risk-scores are needed to better predict those at risk for neurological events in CF-LVADs
Abstract TP394: Comparison of Major Bleeding Endpoints Between Non-vitamin K Antagonist Oral Anticoagulants and Aspirin: A Network Meta-Analysis
Authors: Huang Wen-yi , Singer Daniel E , Wu Yi-Ling , Weng Hsu-Huei , Lee Meng , Ovbiagele Bruce
Published: October 2018

Background:
The favorable risk-benefit of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) vs. warfarin among individuals at high thrombotic risk is well established. However, relatively few trials have directly compared NOACs to aspirin with regard to bleeding outcomes. A Network meta-analysis integrates data from direct comparisons of treatments within trials and from indirect comparisons of interventions assessed against a common comparator in different trials, to compare all investigated treatments.

Objective:
To conducted a network meta-analysis to comprehensively investigate the risks of ICH, major bleeding, and fatal bleeding, for NOACs vs. aspirin.

Methods:
Pubmed and EMBASE from 1966 to June 2017 were searched to identify relevant studies. We included randomized controlled trials that included a comparison of (1) NOACs vs placebo, (2) NOACs vs aspirin, and (3) warfarin vs aspirin, and in which the number of patients and ICH or major bleeding events were reported. Only trials with treatment duration of 3 months or longer were included. We conducted the network meta-analysis utilizing a frequentist model with Stata version 14.

Results:
Literature search identified 34 trials with 110,127 participants. The population varied (e.g. atrial fibrillation, stroke, ischemic heart disease, venous thromboembolism) across trials. Two trials compared NOACs with aspirin, 10 trials compared NOACs with warfarin, and 22 trials compared warfarin with aspirin. Direct comparison showed that both NOACs and aspirin had lower risks of ICH than warfarin (NOAC vs warfarin: OR 0.45, 0.39-0.53; aspirin vs warfarin: OR 0.53, 0.37-0.76) while NOACs and aspirin had similar risk of intracranial hemorrhage (OR 0.87, 0.42-1.80). Network meta-analysis combining direct and indirect comparisons showed NOACs and aspirin had similar risks of intracranial hemorrhage (OR 0.98, 0.32-3.00). Network meta-analysis combing direct and indirect comparisons also showed NOACs and aspirin had similar risks of major bleeding (OR 0.99, 0.20-4.94) and fatal bleeding (OR 0.99, 0.55-1.78).

Conclusions:
This network meta-analysis of randomized controlled trials showed that risks of major bleeding endpoints were not different between NOACs and aspirin across broad populations.
Abstract TP395: Lateralized Periodic Discharges are Predictive of Seizures in Patients With Intracerebral Hemorrhage
Authors: George Pravin , Newey Christopher R
Published: October 2018

Background:
Patients with intracerebral hemorrhages (ICH) have a higher incidence of seizures. Previous studies have suggested that the location and size of hemorrhage may increase epileptogenicity. We aim to evaluate seizure development risk factors from clinical examination, imaging, and continuous electroencephalography (CEEG) in critically ill patients with ICH.

Methods:
We reviewed 57 consecutive patients with ICH admitted to a neurocritical intensive care unit over a 24-month period who were monitored on CEEG. Their demographic and examination data, ICH score, Glasgow coma scale (GCS), location of bleed, CEEG patterns, and discharge status were analyzed.

Results:
Sixteen (28%) patients from our study cohort had seizures at a mean duration of 7.46 hours from CEEG hookup. Fifteen (93%) of those patients had electrographic only seizures. The finding of lateralized periodic discharges (LPDs) was significantly (p=0.019) associated with seizures. Other variables, such as ICH score, size and location of hemorrhage, GCS, mental status, and other CEEG patterns, were not significantly associated with seizures.

Conclusion:
We found that LPDs were predictive of seizures in ICH patients. CEEG for longer than 24-hours is preferred for detection of seizures as they occurred at a mean later than seven hours and most were without clinical signs.
Abstract TP397: Modified Graeb Score Predicts Stress-Induced Hyperglycemia After Subarachnoid Hemorrhage
Authors: Greenert John C , Ross Stephen R , Ford Lance , Thompson David M , Ray Bappaditya
Published: October 2018

Introduction:
Post-hemorrhagic hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH) that can result in homeostatic derangement including stress induced hyperglycemia (SIH). Modified Graeb score (MGS) is a semi-quantitative scoring system that can estimate extent of hydrocephalus and amount of intraventricular blood.

Hypothesis:
We assessed whether MGS can predict SIH after aSAH.

Methods:
On the basis of our previous research with this same cohort, SIH was defined as a ratio of admission serum glucose (AG) to glycated hemoglobin, HbA1c (AG:HbA1c) of 26 or higher. This retrospective study reviewed charts of aSAH patients admitted to a tertiary care hospital. MGS was calculated retrospectively using admission computed tomography (CT) scans. Exploratory loess regression was used to characterize the association between MGS and SIH. Non-parametric tests were used to investigate difference in MGS between those with and without SIH. Fisher’s exact tests assessed differences in prevalence of SIH between patient groups.

Results:
Average age of cohort was 52.3±13.1 years with 65% women. SIH was observed in 72/165 (43.6%) patients. One hundred and eight of the 165 patients (65.5%) were modified Fisher grade 3-4 on admission CT scans. Fifty-five patients (50.9%) with modified Fisher grade 3-4 developed SIH as compared to 17 (29.8%) of patients with modified Fisher grade 1-2 (p=0.013). Locally weighted or LOESS regression showed a positive relationship between the AG:HbA1c ratio at MGS up to about 12. MGS threshold of ≥10 predicted SIH with 88.2% specificity. Although median MGS was higher in patients developing SIH (4; interquartile range or IQR 5.5) as compared to those without SIH (2; IQR 6.0), the difference did not reach statistical significance (p=0.079).

Conclusion:
Higher MGS, indicative of more severe obstructive hydrocephalus, is associated with increased incidence of SIH. This alludes to contribution of hydrocephalus in neurohumoral derangement and associated dysglycemia after aSAH.
Abstract TP404: A Novel Adipokine DPPIV Induces Inflammation and Apoptosis of Carotid Artery Smooth Muscle Cells: Implications for Atherosclerotic Plaque Instability
Authors: Wesley Umadevi V , Jaeger Jacob W , Hatcher James F , Dempsey Robert J
Published: October 2018

Background:
Carotid Atherosclerotic (CA) plaque rupture is associated with ischemic stroke. Smooth muscle cells (SMC) play key role in plaque development. SMC also produce collagen fibers and maintain the fibrous cap thickness and strength, and SMC apoptosis and inflammation can lead to plaque rupture. Molecular mechanisms leading to plaque instability and stroke are not completely understood. Our study has shown that an adipokine dipeptidyl peptidase (DPPIV) is significantly upregulated in post-stroke rat brain, and in the plasma of over 75% of CA patients, suggesting a role for DPPIV in CA and stroke. In this study, we examined the effects of DPPIV on SMC viability, apoptosis, and identified responsible signaling pathways.

Methods:
Mouse carotid artery SMC were exposed to oxygen glucose deprivation (OGD). Cells were treated with either physiological (200-500 ng/ml) or high (1000-2000 ng/ml) dose of DPPIV. Using transcriptome array, we examined the expression profile of apoptotic and inflammatory pathway specific genes in these cells. DPPIV levels were examined by PCR and immunofluorescence staining. MTT assay was used to assess cell viability. Live/dead cell assay detected apoptosis. Mitochondrial membrane potential was detected using tetra-methyl-rhodamine ethyl ester (TMRE).

Results:
Ischemia/hypoxia upregulates DPPIV mRNA and protein levels in association with increased pro-apoptotic genes including caspase 7, Nod1, and Gadd45a. Transcriptome array data demonstrated that higher dose of exogenous DPPIV results in significant increase in same pro-apoptotic pathway genes including caspase 3,7, Nod1, Trp63, and Gadd45a. On the other hand, DPPIV decreased the expression of anti-apoptotic genes including Atf5 and Birc3. Levels of pro-inflammatory cytokines including IL1-beta and Ccl26/Eotaxin were increased in both DPPIV and ischemic SMCs. Higher dose of DPPIV increased apoptosis, decreased viability and mitochondrial membrane potential in SMCs.

Conclusion:
Higher levels of DPP4 activates the inflammatory and apoptotic signaling cascade resulting in the apoptosis of SMC. Further research in this area will enhance our understanding of the mechanism of CA progression and may provide clues to efficient therapeutic intervention for CA.
Abstract TP405: Drastic Changes of Blood-brain Barrier Biomarkers After Direct Bypass Surgery for Moyamoya Angiopathy - A Preliminary Study -
Authors: Ishii Daizo , Matsushige Toshinori , Okazaki Takahito , Shinagawa Katsuhiro , Sakamoto Shigeyuki , Oshita Jumpei , Kurisu Kaoru
Published: October 2018

Objective:
Drastic hemodynamic change can be expected after direct bypass surgery for moyamoya angiopathy (MMA). However hemodynamic hyperperfusion could be observed presumably because of the increased permeability of blood-brain barrier (BBB). The assessment of BBB related molecular proteins has never been investigated. The purpose of this study was to evaluate the perioperative serum levels of biomarkers representing BBB function in MMA patients based on the hypothesis that postoperative hemodynamic change may cause the instability of BBB.

Methods:
A total of 13 hemispheres in 12 patients with MMA were prospectively investigated. A superficial temporal artery - middle cerebral artery direct bypass was performed in all cases. All patients had blood examinations before and postoperative day (POD) 1, 4 and 7, respectively. The serum levels of tight juction proteins (occludin [OCLN] and claudin 5 [CLDN5]) and an adherence junction protein (vascular endothelial [VE]-cadherin) were measured quantitatively using enzyme linked immunosorbent assay. The percent change of these proteins compared to preoperative was calculated.

Results:
Successful patency of the direct bypass was obtained in all cases. No apparent hemorrhagic or ischemic changes were observed on CT and MR image in this study. The mean percent changes of OCLN, CLDN5 and VE-Cadherin on POD 1 were 523.3 ± 598.0%, 108.7 ± 297.0% and -23.9 ± 25.5%, respectively. The following changes of OCLN and CLDN were decreased; -7.7 ± 63.8% and 80.0 ± 320.9% on POD 4 and -9.1 ± 54.2% and 36.3 ± 209.1% on POD 7, respectively. On the other hand, there was no remarkable fluctuation on those of VE-Cadherin in this series. The serum levels of OCLN and CLDN5 on POD 1 were markedly elevated over 10 folds higher than baseline in two patients, who had transient neurological symptoms within 13 days after the surgery.

Conclusion:
In patients with MMA undergone direct bypass surgery, drastic changes of biomarkers representing tight junction of BBB were observed. These preliminary results suggested that marked hemodynamic change and temporary neurological symptom in some patients might be associated with the instability of BBB after direct bypass surgery for MMA.
Abstract TP407: Combination of Minocycline and Neural Stem Cells Ameliorates Neurological Deficit in Aged Stroke Mice With Delayed Tpa Treatment
Authors: Eckert Auston , Hamblin Milton , Lee Jean-Pyo
Published: October 2018

The great promise of using stem cells to treat stroke has been inhibited by challenges to stem cell survival in the toxic environment of post-stroke tissue. Reperfusion (removal of clot) can be achieved mechanically (thrombectomy, <6-8hrs or by tissue plasminogen activator (tPA, <4.5 hrs), but ischemia/reperfusion injury limits the treatment time window. Furthermore, deleterious non-thrombolytic off-target effects of delayed tPA infusion (e.g., >4.5hrs) have been shown within brain parenchyma, increasing vascular injury and death of neurons. Previously, we reported that human neural stem cell (hNSC) transplantation 24hrs after stroke shows multiple beneficial short-term effects within 48hrs post-stroke, reducing inflammation, blood-brain barrier (BBB) damage, and infarct size. Since delayed tPA administration exacerbates BBB damage and increases hemorrhage, we reasoned that ameliorating inflammation and BBB damage by pretreating with neuroprotectants (i.e., minocycline) prior to tPA might synergize to expand the time window for tPA and provide a better environment for NSC survival, thus increasing NSC efficacy. We utilized the middle cerebral artery occlusion stroke mouse model to induce focal cerebral ischemia followed by reperfusion (MCAO/R). 6hrs post-MCAO, we administered tPA intravenously. Minocycline was administered intraperitoneally at various time points prior to tPA injection. One day post-stroke, we injected hNSCs intracranially. Previously, we reported that minocycline pretreatment prior to tPA and hNSC transplantation reduced the mortality of delayed tPA-treated aged mice within 48hrs post-stroke. In this study, we investigated the effect of hNSCs treated with minocycline-plus-delayed tPA treatment on long-term benefits on neurological function. We performed a behavioral test of motor function beginning 24hrs after hNSC transplantation. Rotarod test was carried out 3 days(d) consecutively pre-stroke (as training) and from 2d to 28d post-stroke. Here, we report that by combining minocycline prior to tPA significantly ameliorates neurological deficit in aged mice. Furthermore, transplanting hNSCs ameliorated the pathophysiology caused by delayed tPA.
Abstract TP408: Uric Acid and the Risk of Recurrent Vascular Events and Mortality in Ischemic Stroke Patients: A 5-year Analysis
Authors: Ng Geelyn , Ng Mei Yen , The Ei Zune , Er Bernadette , Quek Amy , Teoh Hock Luen , Chan Bernard , Paliwal Prakash , Sharma Vijay , Seet Raymond
Published: October 2018

Background:
Women have generally lower levels of uric acid compared with men, yet their long-term prognostic impact is unclear in ischemic stroke patients. This study aims to investigate the significance of serum uric acid in relation to 5-year recurrent vascular events and mortality in ischemic stroke patients.

Methods:
Consecutive patients with acute ischemic stroke were recruited from the National University Hospital, Singapore, between January 2011 and December 2012. Demographic, risk factor, stroke etiology and severity information were compared with the development of vascular events (defined as stroke, myocardial infarction, and vascular-related death) and all-cause mortality. Blood samples were collected during their acute hospitalization; in a subset of patients, repeated samples were collected 3-6 months later. Uric acid was measured in serum using the Cobas c111 analyzer (Roche, Germany). The effects of uric acid on vascular events and death were evaluated by Cox proportional hazard models.

Results:
A total of 531 ischemic stroke patients (mean age 59.2 years; 72% men; mean uric acid 357 mmol/l [men], 319 mmol/l [women]) were followed for a mean of 3 years. During this period, 136 vascular events (72% stroke and transient ischemic attack, 18% myocardial infarction and 10% vascular-related death) and 51 deaths were recorded. In women, significant associations were observed between uric acid levels and vascular-related deaths and all-cause deaths (adjusted hazard ratios 1.01 [95% CI 1.00-1.01;
p
=0.008] and 1.01 [1.00-1.01;
p
=0.001] respectively); no association was observed with vascular events. By contrast, no significant association was observed between vascular-related events and deaths in men. 176 patients had uric acid levels repeated. Overall, there was an increase in uric acid levels (326 vs 360 mmol/l; p<0.001, paired t-test) approximately 4 months following stroke onset. These changes, however, did not correlate with subsequent development of vascular and death events in men and women.

Conclusions:
In women, uric acid levels predict long-term vascular death and all-cause mortality in ischemic stroke patients. The sex-specific differences in the association between uric acid and stroke outcomes warrant further investigations.
Abstract TP410: Microcirculatory Impairment is Caused by Independent Mechanisms From Major Arterial Spasm Both in the Acute and Chronic Phase After Experimental SAH
Authors: Kikkawa Yuichiro , Kamide Tomoya , Uramaru Kouichi , Suzuki Kaima , Takeda Ririko , Tsuchiya Ryosuke , Ikeda Shunsuke , Shibata Aoto , Kurita Hiroki
Published: October 2018

Background & Objectives:
The mechanism of microcirculatory disturbance following subarachnoid hemorrhage (SAH) remains to be elucidated. In this study, we investigated the correlation between the cerebral microcirculatory change and the time-dependent alteration of major arterial vasoconstriction after SAH using rabbit SAH model.

Methods:
CT angiography and perfusion were repeated at 0, 1, 6, 24, 48 hours after first hemorrhage for acute changes observation group (n=8), and on days 0, 3, 5, 7 for chronic changes observation group (n=8) using multi-detector raw CT. Regional cerebral blood flow (rCBF), cerebral blood volume (CBV), mean transit time (MTT) and basilar artery (BA) diameter were calculated at each time point.

Results:
In acute group, immediately after hemorrhage, BA narrowed, both CBV and rCBF were decreased and MTT was increased, transiently. After 6 hours, BA narrowed again and both CBV and rCBF were increased progressively. MTT restored over 24 hours. In chronic group, BA narrowing reached a peak on day 5 and restored after day 7. Both CBV and rCBF were persistently decreased after day 3, while MTT was increased after day 5. In both groups, no significant changes were observed in CBV, rCBF and MTT between in BA territory and other territory.

Conclusions:
Delayed cerebral ischemia may be caused by the microcirculatory disturbance which is regulated by independent mechanisms from major arterial vasospasm both in the acute and chronic phase after SAH in rabbit model.
Abstract TP412: Blood Pressure at Presentation of Acute Ischemic Stroke
Authors: Marcus Brian , Wong Ka-Ho , Chauhan Nabeel , de Havenon Adam
Published: October 2018

Introduction:
Blood pressure on presentation and control of blood pressure are known to have associations with functional outcome and stroke severity. The investigators in this study looked to see if certain systolic blood pressures are associated with specific neurological deficits on presentation of acute ischemic stroke.

Hypothesis:
Systolic blood pressure at presentation of acute ischemic stroke will be associated with focal neurological symptoms.

Methods:
We analyzed the 17,398 patients from the International Stroke Trial with confirmed ischemic stroke. Blood pressure was measured immediately before randomization and a neurological examination was performed with seven categories of focal neurological findings. For each neurological finding, a Student’s t-test was used to evaluate for differences in blood pressure mean between patients with or without the finding. Many of the neurological findings were not examined in all patients.

Results:
See attached image.

Conclusions:
Lower systolic blood pressure on presentation of acute ischemic stroke are associated with visual and neglect deficits as compared to motor, brainstem, and cerebellar deficits.
Abstract TP413: Longitudinal Structural Brain Alterations in Cerebral Amyloid Angiopathy
Authors: Fotiadis Panagiotis , Charidimou Andreas , Pasi Marco ,   Alzheimer’s Disease Neuroimaging Initiative, Lee Myung J , Schwab Kristin , Goldstein Joshua N , Rosand Jonathan , Viswanathan Anand , Greenberg Steven M , Gurol M. Edip
Published: October 2018

Background/Purpose:
Cross-sectional studies show associations between cerebral amyloid angiopathy (CAA) and cortical as well as white matter atrophy. We hypothesized that CAA patients also have hastened gray and white matter atrophy in longitudinal follow up.

Methods:
We compared multimodal MRIs from 49 prospectively enrolled non-demented patients with probable CAA (per Boston criteria) scanned at two different time points, to two other longitudinal cohorts: 49 Healthy Controls (HC) and 49 patients with Alzheimer’s Disease (AD) from the AD Neuroimaging Initiative. Validated
FreeSurfer
algorithms were used to calculate Gray Matter (GMV) and White Matter Volumes (WMV), expressed as percentage of intracranial volume (ICV). Cognitive assessments were done for 34 CAA patients during their baseline and follow up visits, and z scores for executive function, processing speed and memory were calculated. Multivariable models were adjusted for age, sex, presence of hypertension, and baseline variable of interest.

Results:
Patients with CAA were of similar age (baseline mean age: 71.1) to HC (72.8, p=0.183) but younger than patients with AD (77.3, p<0.001). In all cohorts, the follow up scans were performed 1.1 years after the initial MRIs. The GMV percent decrease was significantly larger in CAA than HC (1.21%, p=0.030), but significantly worse in AD than CAA (1.52%, p=0.029). The WMV percent decrease was significantly higher in patients with CAA when compared to both HC (1.82%, p=0.006) and patients with AD (1.69%, p=0.016). All of these associations remained significant in multivariable models. The WMV percent decrease within the CAA cohort correlated strongly with the longitudinal percent decrease in executive cognitive scores both in univariable (r=0.58, p=0.0003) and multivariable regression models (p=0.0006).

Conclusions:
Patients with CAA have worse gray matter atrophy than HC as well as worse white matter atrophy than both HC and AD longitudinally, results in line with previous cross-sectional work. The rates of atrophy in CAA also correlated strongly with measures of worsening cognitive function. Our findings support the projected cause-effect relationship between CAA and global brain atrophy leading to cognitive impairment.
Abstract TP417: Cortical Microinfarcts on 3T MRI in Cerebral Amyloid Angiopathy: Associations With MRI Burden and Cognitive Dysfunction
Authors: van den Brink Hilde , Zwiers Angela , Charlton Anna , Switzer Aaron R , McCreary Cheryl R , Goodyear Brad , Frayne Richard , Biessels Geert J , Smith Eric E
Published: October 2018

Background:
Cerebral amyloid angiopathy (CAA) causes vascular cognitive impairment, possibly due to ischemic lesions that are caused by impaired cerebral blood flow. Cerebral microinfarcts (CMIs) are small ischemic lesions that are found in CAA patients at autopsy.

Hypothesis:
Cortical CMIs can be detected on
in vivo
3T MR images in CAA and will correlate with markers of CAA-related vascular brain injury and cognitive function.

Methods:
We analysed data from CAA cases and neurologically healthy controls participating in the Functional Assessment of Vascular Reactivity (FAVR) study. All participants underwent a standardized clinical, neuropsychological and 3T MR assessment. Cortical CMIs were rated according to standardized criteria, by a single rater blinded to clinical information.

Results:
There were 36 CAA patients (mean age 73.0±9.0 years) and 22 healthy controls (69.0±8.3 years). Cortical CMIs were found in significantly more patients with CAA (50%) (median number: 1, range: 1-9) than in healthy controls (18%) (
p
=0.02). In CAA, patients with cortical CMIs had higher white matter hyperintensity volumes (median 29.5 mL vs 13.0 mL,
p
=0.04) and cerebral microbleed counts (median 28 vs 5.5,
p
=0.049). CAA patients with cortical CMIs also showed lower occipital fMRI activation (median BOLD change 1.97% vs 2.57%,
r
=0.24,
p
=0.15) and worse memory performance (mean
z
-score -0.60 vs -0.05,
p
=0.12), although both effects were non-significant. No significant association of cortical CMIs with age, sex or vascular risk factors was found.

Conclusions:
Cortical CMIs are frequently detected on 3T MRI in CAA. They relate to well-established ischemic and hemorrhagic MRI markers of CAA. Therefore
in vivo
cortical CMIs can be regarded as a new marker of CAA disease severity. Additional, larger studies are needed to determine the relationship between CMI and clinical outcomes in CAA.