Abstracts of the Annual Conference of the Asia Pacific Stroke Organization (APSO), September 12-14, 2014, Taipei, Taiwan.

Oral Presentations Cerebrovasc Dis 2014;38(suppl 1):1–114 DOI: 10.1159/000367674

Large Clinical Trials (RCTs)

Published online: September 12, 2014

Analysis: Intention to treat. Trial Status: Recruitment commenced in August 2012 with

12 centres now open in Australia and New Zealand and a further 2 sites planned to open in 2014. F01-1

Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial: The EXTEND-IA Trial Campbell1,

Mitchell2,

Neuroprotection and Rehabilitation

Yan1,

Bruce Peter Bernard Leonid Churilov3, Henry Ma3, Mark Parsons4, Geoffrey Donnan3, Stephen Davis1

Dept. Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Australia; 2Dept. Radiology, Royal Melbourne Hospital, University of Melbourne, Australia; 3Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia; 4John Hunter Hospital, University of Newcastle, Australia

Background: The proven benefits of tPA within 4.5 hours of stroke onset are limited by modest reperfusion rates in patients with major vessel occlusion. Endovascular mechanical clot retrieval may increase reperfusion rates in these patients. Objective: EXTEND-IA will test the hypothesis that dual target vessel occlusion and penumbral mismatch can select patients with favourable response to reperfusion using mechanical clot retrieval after standard IV tPA 1.2. Ischemic core volume, assessed using MR-DWI or CT-relative cerebral blood flow, must be 0.05). When both groups were pooled together, the integrity of the frontostriatal tracts of the affected hemisphere was found to correlate with the tracking performance on day 1 and Day 7 (r = –0.564 to Downloaded by: 203.158.221.15 - 5/16/2015 9:29:42 PM

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–0.685, p < 0.05). When the stroke patients were analyzed alone, such correlation also existed (r = –0.875 to –0.928, p ≦ 0.05). Discussion and Conclusions: The findings suggest that better integrity of the frontostriatal fibers predicted better control and better motor sequence learning outcome.

Neuroimaging

F01-4

Comparison of Whole-Brain CTP and Limited-Coverage CTP

OCT4B-190 Exerts Neuroprotection After Stroke by Modulating GSK-3␤ and HDAC-6 Yanting Chen, Zhengzheng Wu, Xiaolei Zhu, Xuefeng Zang, Jiali Jin, Xiaoxi Li, Yun Xu Dept. of Neurology, Affliated Drum Tower Hospital of Nanjing University Medical School, China

Backgrounds and Objectives: OCT4 is a key regulator in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Human OCT4 gene has three mRNA isoforms, termed OCT4A, OCT4B, and OCT4B1. OCT4A mRNA can translate into OCT4A protein. OCT4B mRNA has been recently found to generate three protein isoforms by alternative translation initiation, including the 265-amino-acid protein isoform OCT4B-265, the 190-amino-acid protein isoform OCT4B-190, and the 164-amino-acid protein isoform OCT4B-164. OCT4A is now widely recognized as a transcription factor responsible for the stemness of ESCs, while the biological functions of OCT4B protein isoforms are still not identified. A previous study showed that OCT4B-190 functioned in stress response. In this study, we further investigated biological roles of OCT4B-190 in stroke setting in vivo and in vitro. Methods and Results: Using primary neuron cultures, we demonstrated that OCT4B-190 overexpression enhanced neuronal viability 24 hr after oxygen-glucose deprivation (OGD) treatment, with downregulated OGD-induced histone deacetylase 6 (HDAC6) and glycogen synthase kinase-3β (GSK-3β). Furthermore, it was shown that HDAC6 and GSK3β were co-expressed in the cytosol of neurons, and OCT4 had an effect on interactions between HDAC6 and GSK3β after OGD that could be mimicked by GSK3β inhibitors. Moreover, in male C57BL/6 mice subjected to transit middle cerebral artery occlusion (tMCAO), OCT4B-190 overexpression reduced post-stroke infarct volume and improved neurological functions at 3d after stroke. In addition, OCT4B-190 demonstrated similar impacts on HDAC6 and GSK3β alterations after MCAO treatment. Conclusions: These evidence suggest that OCT4B-190 exerts neuroprotection potentially by regulating GSK-3β/HDAC6 pathway in ischemic stroke.

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Cerebrovasc Dis 2014;38(suppl 1):1–114 DOI: 10.1159/000367674

Longting Lin1, Andrew Bivard1, Venkatesh Krishnamurthy1, Christopher Levi1,2, Mark Parsons1,2 1Hunter

Medical Research Institute, The University of Newcastle, Australia; 2Department of Neurology, John Hunter Hospital, Australia

Background and Objectives: Traditional CT perfusion (CTP) is limited on axial coverage. With new generation CT scanners, whole-brain coverage is achievable. In this study, we aimed to assess whether whole-brain CTP, compared to limited-coverage CTP, had better performance on measuring ischemic penumbra and infarct core. Methods: 266 patients, who presented within 6 hours of ischaemic stroke onset, were included in the study. Those patients were scanned by 320-detector CTP which had brain coverage of 160 mm. Four other commonly used CTP acquisitions were simulated on the same patient data by progressively limiting to 100 mm (128-detector spiral scanner), to 80 mm (256-detector scanner), to 40 mm (64-detector scanner), and to 20 mm (16-detector scanner). Performance of above scanners was compared in predicting true ischemic lesion in terms of accuracy, precision, sensitivity, and specificity. Accuracy and precision were analysed by Lin’s concordance correlation coefficient (CCC); sensitivity and specificity were derived from Receiver Operating Characteristic (ROC) curve regression. Results: The lesion on acute diffusion weighted imaging (DWI) was used as the reference for true infarct core; for penumbra, the 24-hour DWI lesion in patients with no recanalization was the reference. In predicting both true penumbra and infarct core, 320-detector scanner had great accuracy (≥99%), great precision (≥96%), good specificity (≥91%), and reasonable sensitivity (≥78%). By limiting the brain coverage to 100 mm or 80 mm, accuracy was reduced but CTP still had overall good performance. However, by limiting the coverage to 40 mm, CTP significantly underestimated the ischemic volume, resulting in dramatic drop of accuracy (≤85.10%) and sensitivity (≤48.06%). Limitation of coverage to 20 mm resulted in further drop of accuracy and sensitivity. Conclusion: Compared to limited-coverage CTP, wholebrain CTP had better accurate and sensitive on measuring acute penumbra and infarct core.

Oral Presentations

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F01-3

Acute Stroke Management

F01-6

Correlation of Initial Blood Pressure with Admission Cost and One-Year Outcome in Acute Stroke Patients Low Aspects Score Is Associated with Malignant Middle Cerebral Artery Infarction Caroline Maccallum1, Leonid Churilov3, Peter Mitchell2, Richard Dowling2, Bernard Yan1 1Melbourne

Brain Centre at Royal Melbourne Hospital, the University of Melbourne, Melbourne, Australia; 2Department of Radiology at Royal Melbourne Hospital, the University of Melbourne, Melbourne, Australia; 3The Florey Institute of Neuroscience and Mental Health, Melbourne, Australia

Background: Early decompressive hemicraniectomy following malignant middle cerebral artery (MCA) infarction reduces mortality and improves clinical outcome. Imaging predictors of malignant infarction may serve as ‘red flags’, prompting monitoring and intervention. Our objective is to investigate whether lower ASPECTS (Alberta Stroke Program Early CT Score) is associated with malignant MCA infarction. Methods: Retrospective cohort study of patients with MCA territory ischaemic strokes who were admitted to Royal Melbourne Hospital between 1 January 2009 and 31 December 2009. Results: One-hundred-and-eight patients out of 226 (48%) developed malignant MCA infarction. Good (>0.8) inter-rater agreement between observers scoring ASPECTS was observed. We validated that ASPECTS 7 was the optimal cut-off score to determine progression to malignant infarction, providing 50% sensitivity and 86% specificity. One-hundred-and-fifty-six patients had ASPECTS >7 (69%) and 70 patients had ASPECTS ≤7 (31%). With ASPECTS ≤7, 54 out of 70 patients (77%) developed malignant MCA infarction, compared with 54 out of 156 patients (35%) with ASPECTS >7 (age-adjusted OR = 0.12, 95% CI: 0.06, 0.25; p < 0.0001). If ASPECTS ≤7 is a positive result, the positive predictive value is 77% and the negative predictive value is 65. Median ASPECTS for developing malignant MCA infarction was 7.5 (IQR: 5 to 10), while median ASPECTS for not was 10 (IQR: 8 to 10), resulting in a significant age-adjusted median difference of 2 (95% CI: 0.8, 3.2; p = 0.001). Conclusions: ASPECTS ≤7 is associated with the development of malignant MCA infarction. We recommend close monitoring of, and early consideration of decompressive hemicraniectomy for, acute stroke patients with ASPECTS ≤7.

Asia Pacific Stroke Conference 2014

Chi-Hung Liu1, Yi-Chia Wei2, Jr-Rung Lin3, Chien-Hung Chang1, Ting-Yu Chang1, Kuo-Lun Huang1, Yeu-Jhy Chang1, Shan-Jin Ryu1, Leng-Chieh Lin4, Tsong-Hai Lee1 1

Stroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Department of Neurology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 3Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taiwan; 4Department of Emergency Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

Objectives: To investigate the influence of initial blood pressure (BP) on admission cost and one-year outcome in acute ischemic (IS) and hemorrhagic stroke (HS). Methods: Stroke patients admitted within 3 days after onset in 2009 were recruited. The initial BP on admission was divided into high, medium, and low groups and further subgrouped with 25 mm Hg difference in systole and 10 mm Hg difference in diastole for the correlation analyses of BP to demographics, admission cost and one-year modified Rankin scale (mRS). Results: In 1173 IS patients, low diastolic BP group had higher frequency of heart disease (p = 0.001), dehydration (p = 0.03) and low hemoglobin level (Hb) (p < 0.001). The extreme high and low systolic BP subgroups had worse National Institutes of Health Stroke Scale (NIHSS) (p = 0.002), higher admission cost (p < 0.001), and worse one-year mRS (p = 0.004), while extreme high and low diastolic BP subgroups had higher admission cost (p < 0.001). In 282 HS patients, both low systolic and diastolic BP groups had low Hb level (systole: p = 0.04; diastole: p < 0.001). The extreme high and low BP subgroups had worse NIHSS (p = 0.004 and p < 0.001, respectively), worse one-year mRS (p = 0.004 and p = 0.001, respectively), and higher admission cost (diastole: p < 0.001). Conclusion: Extreme high and low BP on admission not only have higher stroke severity but also cause higher admission cost and/or worse one-year outcome in stroke patients. Low admission Hb might contribute to higher cost and worse one-year outcome in these patients with low BP.


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F01-5

Stroke in Asia

Large Clinical Trials (RCTs)

F01-7

F01-8

A GWAS Identifies Potential Susceptibility Variants for Large-Vessel Ischemic Stroke in a Han Chinese Population

Present Status of J-STARS and Substudies

1Chang

Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan; 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; 3These Authors Contributed Equally to this Work

Stroke is a major cause of acquired disability and the second leading cause of death in adults. The large-artery atherosclerosis (LAA) subtype has been shown to be more strongly correlated with family history than other subtypes. To identify novel genetic variations that predispose individuals to large-vessel ischemic stroke, we conducted a genome-wide association study (GWAS) in 475 individuals with a major ischemic stroke subtype (large artery atherosclerosis, LAA), and 1,727 controls in a Han Chinese population residing in Taiwan. In the discovery stage, we found that there was an association of the loci at 7p21.1 (SNP-4, P = 9.33 × 10–7) in HDAC9 (encoding histone deacetylase 9) that was previously reported in GWAS of European and American individuals. In addition, we also identified 7 novel potential susceptibility variants in the loci at Chr2 (SNP-1, P = 8.30 × 10–6; SNP-2, P = 1.55 × 10–6), Chr7 (SNP-3, P = 1.86 × 10–6; SNP-5, P = 2.74 × 10–8), Chr10 (SNP-6, P = 7.64 × 10–6; SNP-7, P = 5.58 × 10–6), and Chr14 (SNP-8, P = 4.76 × 10–6). New LAA subjects are required for replicating these candidate variants. Our findings may provide a preliminary genetic basis of large-vessel ischemic stroke in a Han Chinese Population.

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1Department

of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan; 2Translational Research Informatics Center, Kobe, Japan; 3National Cerebral and Cardiovascular Center, Osaka, Japan; 4Division of Biostatistics and Clinical Epidemiology, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan; 5Clinical Research Center, International University of Health and Welfare, Center For Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center, Tokyo, Japan; 6Seiai Rehabilitation Hospital, Fukuoka, Japan

Background: In Japan, it is still unclear whether hyperlipidemia is a risk factor of recurrent stroke in the ischemic stroke patients, though statin therapy could decrease the incidence of coronary heart disease and first occurrence of stroke in Japanese patients with hypercholesterolaemia (MEGA study). The neuroprotective mechanism beyond cholesterol-lowering effects could be expected to attenuate cerebrovascular inflammation and atherosclerosis. Objective: This study hypothesizes if the treatment with a low-dose pravastatin (10 mg/day) prevents recurrent stroke in Japanese patients with ischemic stroke with safety. Design: J-STARS is a multicenter, prospective, randomized, open label, blinded-endpoint, active controlled, parallel group trial. Population Studied: Eligibility includes, 1) ischemic stroke from 1 month to 3 years after the onset, except for cardiogenic embolism, 2) 45–80 years old, and 3) total cholesterol level of 180–240 mg/dL without the prescription of statin. Exclusion criteria includes, ischemic stroke of other determined cause according to the TOAST classification, ischemic heart disease necessary to require statin, and hemorrhagic disorders. Interventions: Patients were randomized into the group receiving pravastatin 10 mg/day or that having no statin. Outcome Measures: The primary outcome for this study is cerebrovascular events. The secondary outcomes include the events of ischemic or hemorrhagic stroke, cardiovascular events, death of all causes, hospital admission, dementia, and cognitive impairment. Statistical Analysis: The final analysis will be performed by employing Kaplan-Meier survival method, a stratified log-rank test and Cox proportional hazard model. Trial Status: A total of 1578 patients were recruited from 123 centers by 2009, and completed follow-up at February, 2014

Oral Presentations

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Tsong-Hai Lee1,3, Tai-Ming Ko2,3, Chien-Hsiun Chen2, Ming-Ta Michael Lee2, Yeu-Jhy Chang1, Chien-Hung Chang1, Ko-Lun Huang1, Ting-Yu Chang1, Ku-Chou Chang1, Min-Shen Wen1, Ying-Ting Chen2, Chia-San Hsieh2, Shu-Yu Chou2, Yi-Min Liu2, Hui-Wen Chen2, Hung-Ting Liao2, Chia-Wen Wang2, Shih-Ping Chen2, Yuan-Tsong Chen2, Jer-Yuarn Wu2

Masayasu Matsumoto1, Naohisa Hosomi1, Shiro Aoki1, Masanori Fukushima2, Yoji Nagai2, Kazuo Minematsu3, Chiaki Yokota3, Hideki Origasa4, Shinichiro Uchiyama5, Setsuro Ibayashi6

(mean 4.7 years at January, 2014). Mean age 66.2 years; 25.4% atherothrombotic infarction, 64.2% lacunar infarction. The protocol paper including baseline data has been published (Nagai Y et al., Int J Stroke, 2013). The latest status including substudies (e.g. J-STARS Echo, hsCRP and Genomics) will be presented at the conference.

P = 0.001), but not the low-dose group with HR = 0.85 (95% CI = 0.70–1.03, P = 0.096). Rehabilitation services worked better for ischemic stroke patients rather than hemorrhagic stroke patients. The benefits of rehabilitation seemed applicable to various age groups, sex, stroke severities and comorbidities. Conclusion: This study demonstrated the potential dose-dependent effects of rehabilitation services on reducing the risk of readmission or mortality after stroke irrespective of age, sex, stroke severity or comorbidity in a health care level. However, the effects were not identified in hemorrhagic stroke patients.

Neuroprotection and Rehabilitation Hemorrhage – Intraparenchymal F01-9

Hsuei-Chen Lee1, Ku-Chou Chang2, Chung-Lin Yang1, Jen-Wen Hung3, Ching-Yi Wu4, Yu-Ching Huang2, Pei-Chun Lin5, Hui-Hsuan Wang6 1

Department of Physical Therapy and Assistive Technology, National Yang-ming University, Taiwan; 2Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Taiwan; 3Department of Rehabilitation Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan; 4 Department of Occupational Therapy & Graduate Institute of Behavioral Science, Chang Gung University, Taiwan; 5 Department of Rehabilitation, Tri-service General Hospital, Taipei Clinic Center, Taiwan; 6Department of Health Care Management, Chang Gung University, Taiwan

Background and Objectives: Stroke rehabilitation aims to minimize functional disability and prevent complications. This study explored the impacts of rehabilitation services on morbidity and mortality outcomes after stroke in a health care level. Methods: This retrospective cohort study utilized claims data of the National Health Insurance program in Taiwan. A cohort of first-ever acute stroke patients with onset between 2004 and 2005, and survived from initial hospitalization (N = 4,594) were assembled to be followed up until the occurrence of first outcome event (OE) or the end of 2007. OE1 was defined as all-cause readmissions/mortality, while OE2 was all-cause mortality. The volume of rehabilitation services was categorized into none, low-dose and high-dose groups according to the combined amount of inpatient and outpatient rehabilitation. Cox proportional hazards regression model was used to estimate the dose-dependent effects of rehabilitation services on OE1 and OE2 after adjusting for other demographic, clinical and facility characteristics. Results: Within the mean follow-up period of 19 months, the utilization rate of inpatient or outpatient rehabilitation was 45.8%, including: 47.2%, 58.6%, 53.9%, 19.6%, and 36.2%, in SAH, ICH, CI, TIA and unspecified patients, respectively. As compared with none-rehabilitation, OE1 was reduced in high-dose group with HR = 0.90 (95% CI = 0.82–0.99, P = 0.026) and low-dose dose group with HR = 0.70 (95% CI = 0.64–0.77, P < 0.001). OE2 was reduced in high-dose group with HR = 0.73 (95% CI = 0.60–0.88,


F02-1

The Pilot Clinical Study of PG2 Injection on Hemorrhagic Stroke Chun Chung Chen, Der Yang Cho Department of Neurosurgery, China Medical University Hospital, Taiwan

Background and Objectives: Intracerebral hemorrhage (ICH) is a subtype of stroke with high morbidity and mortality, accounting for approximately 15% of all deaths from stroke. PG2 is a sterile powder of polysaccharides isolated from Astragalus membranaceus (AM). The aim of this double-blind, randomized, placebo-controlledclinical trial was to test the efficacy of PG2 on hemorrhagic stroke. Methods: Patients with acute hemorrhageic stroke were randomized within 24 hours of sympotoms onset to control group (saline solution) or treatment group (PG2 500 mg in 500 ml saline) given as intravenous infusion for 3 days per week x 2 weeks from second day of admission, in addition to standard ordinary treatment. The patients were followed up to 12 weeks. The primary outcome measures were the differences in patients’ scores on several clinical scales, between baseline (within 7±1 days after the onset of stroke) and week 4 (28±4 days), and between at baseline and week 12 (84±10 days). The scales we used FIM, BI, Glasgow Outcome Scale (GOS), and Modified Rankin Scale (MRS). Result: A total of 47 patients (Control Group 25, Treatment Group 22) completed the trial. No statistically significant difference were found between the two groups in baseline datas. In the 84 th days, the percentage of GOS in 4-5 in placebo group was 56%, and 86.4% in treatment group. The percentage of MRS in 0-2 in placebo group was 56%, and 81.8% in treatment group (p = 0.05). Conclusion: Hemorrhagic stroke patients who received PG2 injection were highly improved the ability of daily activities (GOS 4-5, mRS 0-2) compared with those without received PG2 injection with significantly difference in the 84th day after stroke. This pilot study have a limitation of poor simple size, a further large study is need to confirm the efficiency of PG2 Injection in hemoeehage stroke.


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Rehabilitation after Stroke Reduced the Incidence of Readmission and Mortality

Stroke in Asia

F02-2

Increased Risk of Stroke Among Patients with Crohn’s Disease in Taiwan: A Population-Based Matched-Cohort Study Joseph Keller1, Jui Wang1, Chia-Chi Chou2,3, Li-Hsuan Wang4, Jung-Lung Hsu5,6,7, Chyi-Huey Bai8, Hung-Yi Chiou1,9,10 1School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taiwan; 2Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan; 3School of Medicine, Chang Gung University, Taiwan; 4School of Pharmacy, College of Pharmacy, Taipei Medical University, Taiwan; 5Graduate Institute of Biomedical Informatics, Taipei Medical University, Taiwan; 6Department of Neurology, Shin Kong Wu Ho-su Memorial Hospital, Taiwan; 7Institute of Biomedical Engineering, National Taiwan University, Taiwan; 8School of Public Health, College of Medicine, Taipei Medical University, Taiwan; 9Stroke Research Center, Taipei Medical University, Taiwan; 10Health and Clinical Research Data Center, Taipei Medical University, Taiwan

Results: After adjusting for selected medical co-morbidities and recent prescriptions of selected pharmaceuticals, the hazard ratio (HR) for subsequent stroke among patients with CD was found to be 1.911 (95% CI = 1.65–2.22) that of comparison subjects. While we did not detect an association between stroke and CD among patients aged 30–40 years, we did detect increased risks for stroke among CD patients aged 40–50 years (HR = 2.29) and those aged over 50 years (HR = 1.88). We also found women (HR = 2.39) to be at a greater risk than men (HR = 1.50). Conclusion: This is study reports an increased HR for subsequent stroke among CD patients when compared to matched comparison patients without IBD in an Asian population.

Hemorrhage – Intraparenchymal

F02-3

Withdrawn

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Oral Presentations

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Background: The risk of venous thromboembolism (VTE) and the development of atherosclerosis are increased in patients with inflammatory bowel disease (IBD). Crohn’s disease (CD) is one type of IBD, however there is controversial information in the literature regarding the association between CD and stroke with no reports being made from an Asian population. The present cohort study estimated the risk of subsequent stroke among CD patients compared with matched comparison subjects drawn from a population-based dataset in Taiwan. Method: This investigation analyzed administrative claims data sourced from the Taiwan National Health Insurance Database. Our study consisted of a study cohort comprising 3,309 CD patients, and a comparison cohort of 13,236 subjects without IBD. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses investigating the risk of subsequent stroke by age group and gender.

TIA and Minor Stroke

Experimental and Translational Neuroscience

F02-4

Tomoyuki Ohara, Toshiyuki Uehara, Rieko Suzuki, Shoichiro Sato, Mikito Hayakawa, Kazunori Toyoda, Kazuo Minematsu Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Japan

Background and Objectives: Identification of atrial fibrillation (AF) and initiation of anticoagulant therapy in transient ischemic attack (TIA) patients are efficient strategies for stroke prevention. The aim of this study was to identify clinical and radiological predictors of AF in TIA patients. Methods: We enrolled 1,338 TIA patients (69±12 years old, men 65%) within 7 days after onset from July 2011 through December 2013 in a multicenter prospective TIA registry, excluding 22 non-AF patients with prosthetic valve or pacemaker implantation. Clinical and radiological features associated with AF in TIA patients were analyzed using multiple regression analysis. Results: Of 1,338 TIA patients, 226 (17%) had AF. AF was previously known or documented at the first presentation in 200 patients, whereas paroxysmal AF was newly identified by monitoring after presentation in 26 patients. In multivariable analysis, age ≥78 years (AF 46% vs. non-AF 24%; Odds ratio [OR] 1.94, 95% confidence interval [CI] 1.38–2.70), absence of dyslipidemia (51% vs. 34%; OR 1.79, 95% CI 1.30–2.45), cortical symptom for TIA symptoms (35% vs. 17%; OR 2.16, 95% CI 1.52–3.04), single TIA episode before presentation (88% vs. 74%; OR 2.19, 95% CI 1.41–3.54) and acute infarcts on diffusion weighted images (DWI) (48% vs. 30%; OR 2.18, 95% CI 1.59–2.99) were associated with AF in TIA patients. Of 1136 patients without known AF at entry, 279 patients had 3 or more of these 5 factors; of these, 18 patients (6.5%) were later diagnosed as having AF. The OR (95% CI) of having 3 or more factors for new identification of AF was 7.34 (3.26–18.06) [sensitivity/specificity; 69%/ 77%]. Conclusion: Advanced age, absence of dyslipidemia, single TIA episode, cortical sign and positive DWI findings were independently associated with the presence of AF in TIA patients. When TIA patients have these factors, extensive examination for identifying AF may be needed.


F02-5

Intracerebral Implantation of Autologous (CD34) in Old Ischemic Stroke Patients: Aphase II Randomized Controlled Trial Der-cherng Chen1,3,4, Shinn-zong Lin1,3, Der-yang Chou1,3, Woei-cherng Shyu2,3 1Dep.

of Neurosurgery, China Medical University and Hospital, Taiwan; 2Dep. of Neurology, China Medical University and Hospital, Taiwan; 3Center for Neuopsychiatry, China Medical University and Hospital, Taiwan; 4Graduate Institute of Clinicalmedical Science, China Medical University, Taiwan

Background: We have demonstrated that peripheral blood hematopoietic stem cells (CD34+ PBSCs) transplantation have been shown to improved the neurological deficit after old cerebral infarction in a previous animal study. 1 We next examined thefeasibility and efficacy of using intracerebral implantation of PBSCs mobilized by granulocyte colony stimulating factor (G-CSF) to treat patients suffering from old stroke. Methods: We did a randomized, controlled study in 30 patients suffered from old cerebral infarction (middle cerebral artery territory as documented on the T2 weighted image [T2WI] of MRI) between 6 months and 5 years of onset who had initial scores on the National Institute of Health stroke scale (NIHSS) of between 9 and 20. After determining eligibility, we randomly assigned them into two groups: PBSC implantation group (n = 15) and control group (n = 15). The PBSC-treated group received subcutaneous G-CSF injections (15 μg/kg per day) for five consecutive days was operated for stereotactic implantation of CD34+ immunosorted PBSCs. We used the following clinical scales as primary end point to assess neurological recovery: National Institute of Health Stroke Scale (NIHSS), European Stroke Scale (ESS), and ESS Motor Subscale (EMS) and Modified Rankin Scale (mRS). In this trial, all clinical information and evaluation data from each patient were assessed blindly by the data recorders and clinicians. Patients have been followed for 12 months. The primary outcomes were assessed by group percentage changes between baseline and 12-month follow-up in mean group scores on 4 clinical scales. In the secondary end point, we also monitored the asymmetry indices of fiber numbers (FNA) in corticospinal tract (CST) integrity using diffusion tensor image tractography (DTI), and examined the electrophysiological conductance in motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS).


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Predictors for Atrial Fibrillation in Patients with Transient Ischemic Attack

Vascular Cognitive Impairment/ Vascular Dementia


F02-7

Association between Carotid Stenosis/ Lacunar Infarction and Incident Dementia in Patients with Vascular Risk Factors Kazuo

Kitagawa1,2,

Shinichiro

Uchiyama1,3

1Department

of Neurology, Tokyo Womens Medical University, Japan; 2Department of Neurology, Osaka University, Japan; 3Clinical Research Center, International University of Health and Welfare, Japan

Background and Purpose: Involvement of vascular risk factors on dementia has attracted much attention. Several prospective studies have shown that the presence of cerebral small vessel disease (SVD) is associated with incident dementia. However, the significance of cerebral large vessel disease (LVD) on dementia development has not been examined thoroughly. Methods: Between 2001 and 2009, 1,106 outpatients who had vascular risk factors were enrolled for prospective study. Among them, 600 patients who underwent brain MRI and had normal cognitive function were included in this study. Follow-up data for dementia occurrence were collected in June 2011. Baseline MRI was used to determine lacunar infarction as a sign of SVD. The presence of carotid stenosis as a sign of cerebral LVD was defined with 50% or more stenosis in carotid ultrasound. Results: Among 600 subjects (mean: 68 years, male: 57%), 264 patients (44%) had lacunar infarction, and 94 patients (16%) showed carotid stenosis. During the follow-up period of median 7.5 years, 50 patients had incident dementia (24 AD, 18 vascular dementia, 5 mixed types, 3 others). The presence of lacunar infarction had close association with dementia in Kaplan-Meier plots analysis (p < 0.001). The association remained significant after adjustment with modifiable factors including history of stroke, APOE genotype and education year. However, the presence of carotid stenosis was not associated with incident dementia after adjustment with age and sex. Conclusion: This study suggested that carotid stenosis have little association with future dementia while lacunar infarction had significant association. The impact of SVD on dementia could be much greater than that of cerebral LVD.

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EP1 Deletion Exacerbate Hemorrhagic Injury by Delaying Microglial Phagocytosis Nilendra Singh1, Sylvain Dore2 1Novel

Drug Discovery and Development, Lupin Research Park, Pune, India; 2Dept. of Anesthesiology, Neuroscience, Neurology, and Psychiatry, University of Florida, Gainesville, FL, United States of America

Background: Prostaglandin E2 (PGE2) has been reported to have various cytoprotective or toxic properties in neurological conditions. The role of the PGE2 EP1 receptor in intracerebral hemorrhage (ICH) induced brain injury has not yet been fully investigated so we performed this study to investigate the role of the EP1 G-protein-coupled receptor in hemorrhagic stroke. Methods: ICH was induced in 2.0–2.5 month-old male C57BL/6 (WT) and EP1 knockout mice by intrastriatal injection of collagenase. Functional outcomes were evaluated at 24, 48, and 72 h post-ICH. Lesion volume, cell survival and death, were assessed using Cresyl Violet, and Fluoro-Jade staining, respectively. Microglial activation and phagocytosis were estimated using Iba1 immunoreactivity and fluorescently-labeled microspheres. All values are expressed in (mean±SEM), and the number of cells/field was provided by averaging four different regions around the hematoma. Results: Collagenase produced a reproducible hematoma that was primarily restricted to the striatum. Following 72 h post-ICH, EP1–/– mice showed deteriorated functional outcomes compared to the WT mice as indicated by elevated neurological deficits, exacerbated lesion volume, and significantly worsened sensorimotor functions. Fluoro-Jade staining showed significantly increased numbers of degenerating neurons and reduced neuronal survival in EP1–/– compared to WT mice. Quantification using Iba1 immunostaining demonstrated a 72% increase in the number of immunoreactive microglia appearing in WT than in EP1 mice. Further, to assess in vivo phagocytosis, the number of microspheres phagocytosed by Iba1-positive cells was 145.4±15.4% greater in WT compared to EP1–/– mice. Conclusion: These data demonstrate that EP1 deletion exacerbates neuro-behavioral impairments and worsen hemorrhagic injury potentially by impairing microglial phagocytosis.

Oral Presentations

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F02-6

Experimental and Translational Neuroscience

F02-8

Experimental Model of Lacunar Infarcts in Mice with Long-Lasting Functional Disabilities Hiroki Uchida1, Hiroyuki Sakata1, Miki Fujimura1, Kuniyasu Niizuma1, Mari Dezawa2, Teiji Tominaga1 1Department

of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Japan

Background: Lacunar infarcts account for 25% of all ischemic strokes. Once thought to be a small vessel disease with a favorable outcome, recent studies have shown the relatively poor long-term prognosis after lacunar infarcts. Limited pre-clinical modeling has hampered understanding of the etiology and development of treatments for this disease. Therefore, we aimed to develop a new experimental model of lacunar infarcts in mice to investigate the pathophysiological changes in the corticospinal tract and to assess the long-term behavioral performance. Method: The vasoconstrictor peptide, endothlin-1 (ET-1), in combination with nitric oxide synthase inhibitor, N(G)-nitro-Larginie methyl ester (L-NAME), was injected in the internal capsule in mice. Histological and behavioral tests were examined from weeks 0–8 after injection. Result: ET-1/ L-NAME injection resulted in severe neurological deficits which continued for up to 8 weeks. Loss of axons and myelin surrounded by reactive gliosis was identified in the region of injection where vasoconstriction of the microvessels was observed. Moreover, tract tracing study revealed the interruption of the axonal flow at the internal capsule. Conclusion: These results indicate that the present novel model in mice, which exhibits long-lasting neurological deficits, is a simple and reproducible approach for using in further investigation for preclinical studies in lacunar infarcts.

repression and show great potential for ischemic stroke therapy. However, the effect of MSCs regarding the protection of ischemiainduced blood-brain barrier (BBB) breakdown is unknown. In the present study, we tested whether MSC therapy benefited bloodbrain barrier integrity and explored the molecular mechanism of aquaporin-4 on blood-brain barrier integrity. Adult CD1 male mice underwent 90 minutes transient middle cerebral artery occlusion and then received 2X105 MSCs transplantation. Neurological severity score, blood-brain barrier permeability and edema formation were evaluated after transient ischemia. We investigated the relationship between MSC transplantation and ischemia-induced apoptotic astrocytes, aquaporin-4 and inflammatory cytokines IL-1β, IL-6, and TNF-α expression in vivo. We then used a conditional medium from LPS-activated microglia to stimulate cultured astrocytes and determined the effect of aquaporin-4 on blood-brain barrier integrity in vitro. Moreover, we explored the regulatory mechanism of aquaporin-4 in relation to the MAPK signaling pathway. We demonstrated that the neurological severity score was greatly improved and ischemia-induced brain edema, IgG protein and Evans Blue leakage were greatly reduced in MSC treated mice compared to the control mice after transient middle cerebral artery occlusion (p < 0.05). MSC therapy efficiently decreased astrocyte apoptosis and inhibited ischemia-induced aquaporin-4 over-expression (p < 0.05). We further demonstrated that conditional medium from LPS-activated microglia effectively enhanced aquaporin-4 expression, p38 and JNK phosphorylation and apoptosis in cultured astrocytes (p < 0.05). MSC treatment resulted in less inflammatory cytokine expression in LPS-activated microglia, which thereby induced milder up-regulation of aquaporin-4 in astrocyte cultures and less apoptosis. Knockdown of aquaporin-4 in cultured astrocytes also reduced apoptosis (p < 0.05). Treatment with p38 and JNK inhibitors demonstrated that p38, but not the JNK signaling pathway is responsible for the aquaporin-4over-expression (p < 0.05). MSCs protected BBB integrity by reducing the apoptotic astrocytes, which was due to attenuated inflammatory response and down-regulated aquaporin-4 expression after ischemic attack. Moreover, mechanistic study showed that inflammatory response up-regulated aquaporin-4 by activating the p38 signaling pathway.

Uncommon Stroke Disorders F02-9 F03-1

Airplane Stroke Syndrome

Guanghui Tang, Yanqun Liu, Zhijun Zhang, Yongting Wang, Guo-Yuan Yang

Hani Humaidan, Nawaf Yassi, Louise Weir, Stephen Davis, Atte Meretoja

Neuroscience and Neuroengineering Research Center, Med-x Research Institute Shanghai Jiao Tong University, China

Melbourne Brain Centre at the Royal Melbourne Hospital, Australia

Cerebral ischemia up-regulates aquaporin-4 expression, increases blood-brain barrier permeability, and induces brain edema. Mesenchymal stem cells (MSCs) exhibit inflammatory cytokine

Background and Objectives: Stroke can occur during or soon after long haul flights, but only 18 cases have been published to date as small series or single case reports. To further understand



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Mesenchymal Stem Cells Maintain Blood-Brain Barrier Integrity by Inhibiting Aquaporin-4 During Cerebral Ischemia

this condition, we describe all identified cases treated at the Royal Melbourne Hospital, Australia. Methods: In this retrospective, observational, single-center study we searched our local prospective stroke database and all discharge summaries from 9/2003 to 4/2014 for flight-related strokes and included any strokes that occurred during or within 2 weeks of a flight. We describe the patient, stroke, and flight characteristics. Results: During the study period, 23 million international and 103 million domestic passengers arrived at Melbourne Airport. We identified 38 patients with flight-related stroke, median age 64 years (range 41–87), baseline NIHSS 10 (1–25), 53% male. Median flight duration was 10:42 (1:30–21:30) and distance 8204 km (713 km; Sydney – 16898 km; London). The stroke occurred inflight (n = 11), within 2 days post flight (n = 15), or 3–14 days post flight (n = 12). Six patients had intracerebral haemorrhage. The TOAST etiology of the remaining strokes was large artery atherosclerosis (n = 2); cardioembolic (n = 12); small vessel disease (n = 1); dissection (n = 3); or undetermined (n = 14). The cardioembolic group included 6 patent foramen ovale (PFO), 1 atrial septal defect (ASD), 3 atrial fibrillation, 1 endocarditis, and 1 aortic arch atheroma cases. Paradoxical embolism was confirmed in 2 patients (PFO + deep venous thrombosis; ASD + pulmonary embolism). Patients were discharged home (47%), to interstate/overseas hospitals (29%), or to local rehabilitation (24%). Conclusions: Stroke related to air travel is a rare occurrence, probably less than 1 in a million. In our series, most strokes occurred during or within 2 days of the flight, which was typically long. Distribution of stroke etiologies was diverse as one would expect in this relatively young age group.

performed when neurological deteriorated or 24–36 hours after thrombolysis. Modified Rankin Scale was evaluated at 90 days. Result: A total of 77 patients had any parenchymal hemorrhage (20.4%), 14 of those had sICH (3.7%) per Safe Implementation of Treatments in Stroke definition, 19 (5.0%) per National Institute of Neurological Disorders and Stroke definition, and 18 (4.8%) per European Cooperative Acute Stroke Study II; 67.5% of patients had a dependent outcome (mRS >= 2). In logistic regression, HbA1c was associated with parenchymal hemorrhage (OR: 4.74, CI: 0.52–0.97, p = 0.03); onset glucose was associated with independent outcome (OR: 3.47, CI: 0.99–1.00, p = 0.063). Conclusion: In our study, HbA1c was tending to be an important predictor of sICH and onset glucose of better functional outcome after thrombolysis for acute stroke. sICH after thrombolysis may be a consequence of long-term vascular injury rather than of acute hyperglycemia, and HbA1c may be a better parameter than acute blood glucose to predict sICH. Hyperglycemia is associated with enhanced cortical toxicity and larger infarct volumes following focal cerebral ischemia and onset glucose may be a better predictor for independent outcome.

Cerebrovascular Occlusive Disease

F03-3

Clinical and Angiographic Features and Stroke Types in Adult Moyamoya Disease


Dong-Kyu Jang1, Kwan-Sung Lee2, Hyung-Kyun Rha3, Pil-Woo Huh4, Ji-Ho Yang5, Ik Seong Park6, Jae-Geun Ahn7, Jae Hoon Sung8, Young-Min Han1 1

Glycated Hemoglobin A1c and Onset Glucose Level Predicts the Safety and Efficacy after Stoke Thrombolysis Meng-Tsang Hsieh1, Chih-Hung Chen1,2 1

Department of Neurology, National Cheng-kung University Hospital, Taiwan; 2Stroke Center, National Cheng-kung University Hospital, Taiwan

Background: Symptomatic intracerebral hemorrhage (sICH) is one of life-threatening complications after intravenous thrombolysis. Onset hyperglycemia was associated with sICH and poor stroke outcome after thrombolysis. The aim of this study was to determine the association between glycosylated hemoglobin A1 (HbA1c) and onset glucose level and safety and efficacy after stroke thrombolysis. Method: In this retrospective study, 378 ischemic stroke patients were treated with intravenous thrombolysis. Onset glucose level was determined when admission and HbA1c was obtained within hospital stay. The second head computed tomography was

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Purpose: The association between clinical and angiographic characteristics and stroke types in adult MMD has been rarely evaluated. Materials and Methods: We analyzed the clinical and radiological data obtained from a retrospective adult MMD cohort with acute strokes, which were classified into 7 categories: largeartery infarct, hemodynamic infarct, perforator infarct, deep intracerebral hemorrhage, lobar intracerebral hemorrhage, intraventricular hemorrhage, and SAH. With conventional angiography, which

Oral Presentations

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F03-2

Incheon St. Mary’s Hospital, the Catholic University of Korea, College of Medicine, Korea; 2Seoul St. Mary’s Hospital, the Catholic University of Korea, College of Medicine, Korea; 3Yeouido St. Mary’s Hospital, the Catholic University of Korea, College of Medicine, Korea; 4 Uijeongbu St. Mary’s Hospital, the Catholic University of Korea, College of Medicine, Korea; 5Daejeon St. Mary’s Hospital, the Catholic University of Korea, College of Medicine, Korea; 6Bucheon St. Mary’s Hospital, the Catholic University of Korea, College of Medicine, Korea; 7 St. Paul’s Hospital, the Catholic University of Korea, College of Medicine, Korea; 8St. Vincent’s Hospital, the Catholic University of Korea, College of Medicine, Korea

was performed in the hemispheres with acute strokes, the Suzuki angiographic stage, major artery occlusion, and collateral vessel development were confirmed within 1 month of stroke onset. Results: This study included 79 acute ischemic and 96 acute hemorrhagic patients. The angiographic stage had a strong tendency to be more advanced in the hemorrhagic than the ischemic patients (P = 0.061). Intracranial aneurysms were more frequently found in the hemorrhagic than ischemic or control hemispheres (P = 0.002). Occlusions of the anterior cerebral artery and development of fetal-type posterior cerebral artery were more frequently observed in the hemorrhagic than the ischemic (P = 0.001 and 0.01, respectively) or control hemispheres (P = 0.011 and 0.013, respectively). MCA occlusion (P = 0.039) and collateral flow development, including the ethmoidal Moyamoya vessels (P = 0.036) and transdural anastomosis of the external carotid artery (P = 0.022), occurred more often in the hemorrhagic than the ischemic hemispheres. Anterior cerebral artery occlusion occurred more frequently in patients with deep intracerebral hemorrhage or intraventricular hemorrhage than with lobar intracerebral hemorrhage (P = 0.009). Conclusions: In adult Moyamoya disease, major artery occlusion and collateral compensation occurred more often in the hemorrhagic than in the ischemic hemispheres. Thus, anterior cerebral artery occlusion with or without MCA occlusion and intracranial aneurysms may be the main contributing factors to hemorrhagic stroke in adult patients with Moyamoya disease.


Timothy Ang1,4, Christopher Levi1,4,6, Henry Ma2,9, Chung Hsu5,10, Bruce Campbell3,8, Geoffrey Donnan7,8, Stephen Davis3,8, Mark Parsons1,4 2

John Hunter Hospital, Australia; Monash Medical Centre, Australia; 3Royal Melbourne Hospital, Australia; 4University of Newcastle, Australia; 5China Medical University, Taiwan; 6 Hunter Medical Research Institute, Australia; 7Florey Neuroscience Institute, Australia; 8University of Melbourne, Australia; 9Monash University, Australia; 10National Health Research Institute, Taiwan

Background: Multimodal CT to guide decision-making for thrombolysis is increasingly used but there remains a perceived risk of contrast-induced nephropathy (CIN). At our centre, patients being assessed for thrombolysis have multimodal CT (total contrast dose 150 mL for perfusion CT and CT angiography) without waiting for baseline serum creatinine, so as not to delay treatment. We routinely give intravenous saline 80–125 mL/hour for the first 24 hours after multimodal CT. We investigated the incidence of contrast-induced nephropathy (CIN), defined as a 25% or more

The PLAN Score Predicts Poor Outcome Following Intracerebral Hemorrhage Wanliang Du, Gaifen Liu, Xingquan Zhao, Yongjun Wang Beijing Tiantan Hospital, Capital Medical University, China

Background and Purpose: The PLAN clinical prediction rule identifies patients who will have a poor outcome after hospitalization for acute ischemic stroke (AIS). We aimed to validate the PLAN score for death and severe disability after intracerebral hemorrhage (ICH). Methods: We analyzed data from a registry of 2453 patients hospitalized with ICH and included in the China National Stroke Registry (CNSR) (September 2007 to August 2008; 132 urban hospitals in China). Outcome measures were 30-day and 1-year mortality and a modified Rankin score of 5 to 6 at discharge. Results: Overall 30-day mortality was 11.5%. The PLAN score (derived from preadmission comorbidities, level of consciousness, age, and neurologic deficit) predicted 30-day mortality (C statistic, 0.82), death or severe dependence at discharge (0.84), and 1-year mortality (0.82). Conclusions: The PLAN score can predict 30-day mortality, death or severe dependence at discharge after ICH in a similar way to the AIS, identify patients who will have a poor outcome after hospitalization for ICH.


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Multi-Modal CT in Acute Stroke: Wait for a Serum Creatinine Before Giving Intravenous Contrast? No!



F03-5

F03-4

1

increase in baseline creatinine levels within 72 hours of contrast administration, and persistent renal impairment in patients receiving multimodal CT. Methods: We analysed 667 patients who underwent multimodal CT studies for evaluation of acute ischemic or hemorrhagic stroke at a tertiary referral stroke centre during the last 5 years. Retrospectively, we analysed serial creatinine levels (baseline to day 3) and later values (≥day 4). The incidences of CIN and/or development of persistent renal impairment (>25% in serum creatinine after day 4) were documented. Results: None of the 667 patients developed symptomatic renal disease or required dialysis. Of 601 patients with serial creatinine measurements between baseline and day 3, seventeen (2.8%) developed CIN. None had a clinically significant deterioration in renal function. All but two of the CIN patients had improvement in renal function after day 4. Of the 667 patients (all had baseline and a repeat serum creatinine ≥day 4), only five (0.7%) had a persistent >25% increase in serum creatinine, none were symptomatic (in fact, none had an eGFR 0.05). Set by Tmax >6 s threshold, good agreement was achieved between CTP and MRP (CCC >0.90). Cross-modality reperfusion, calculated by Tmax >6 s, strongly predicted good clinical outcome at 90 days (AUC = 0.98, P < 0.05). Reperfusion index >77% predicted the good outcome with 94.12% sensitivity and 93.33% specificity. Conclusion: With the right setting, reperfusion can be measured accurately across imaging modalities.

Oral Presentations

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Huaguang Zheng1, Dapeng Mo1, Yilong Wang1, Shiqing Mu1, Jingjing Lu1, Yi Ju1, Hui Qu1, Qidong Chen1, Heng Zhou2, Liping Liu1, Zhonghua Yang1, Xinghu Zhang2, Chunxue Wang1, Kehui Dong1, Xingquan Zhao1, Zhongrong Miao1, Yongjun Wang1

TIA and Minor Stroke

Heart and Brain

F03-8

S03-O1

Factors Affecting Motor Deterioration in Acute Deep White Matter Infarction

Antiepileptic Drug and Cardiovascular Risk in Patients with Epilepsy

Moamina Ismail1, Wing Chi Fong1, Kwok Wing Tang2, Hiu Ming John Chan1, Chung Ki Patrick Li1

Cheng-Yang Hsieh1,2, Chin-Wei Huang3, Yea-Huei Kao Yang2

of Medicine, Queen Elizabeth Hospital, Hong Kong; 2Department of Radiology and Imaging, Queen Elizabeth Hospital, Hong Kong

Background and Objective: A substantial amount of patients with acute deep white matter infarction suffered from progressive motor deficits. This study aims to determine its predictors, so as to generate hypothesis of the underlying pathogenesis and potential preventive or therapeutic strategies. Methods: 54 patients with acute deep white matter infarction were prospectively evaluated by daily National Institutes of Health Stroke Scale (NIHSS) motor score. Motor deterioration was defined as drop in NIHSS motor score of more than or equal to 1 point during the first 7 days. Patients with and without motor deterioration were compared on their clinical and radiological parameters. Results: 11 patients (20.4%) had motor deterioration. They had higher mean diastolic blood pressure in the first 24 hours (88.1±17.2 mm Hg; vs. 79.0±10.9 mm Hg, p = 0.033); elevated haemoglobin level (14.6±1.2 g/dL vs. 13.2±1.6 g/dL, p = 0.007); elevated haematocrit level (0.433±0.035 vs. 0.392±0.043, p = 0.005); elevated white cell count (7.1 [6.0–7.9]; vs. 8.5 [7.3–9.2], p = 0.025); elevated total protein level (73 [70–75] vs. 76 [73–81], p = 0.03); elevated total cholesterol (5.5±1.5 mmol/L; vs. 4.6±1.0 mmol/L, p = 0.01); elevated low density lipoprotein (LDL) cholesterol (3.6±1.3 mmol/L vs. 2.7±0.8 mmol/L, p = 0.005) and elevated urine albumin to creatinine ratio (5.1 mg/mmol [2.0–8.4]; vs. 1.45 mg/mmol [0.7–2.6], p = 0.019). After logistic regression analysis, LDL cholesterol higher than 3.2 mmol/L (relative risk 11.85; 95% CI 1.95–72.09; p = 0.007; table 2) and urine albumin to creatinine ratio higher than 3.5 (relative risk 8.02; 95% CI 1.32– 48.8; p = 0.024) were independent predictive factors for progressive motor deterioration. Conclusion: Progressive motor deterioration in acute deep white matter infarction was independently associated with elevated LDL cholesterol and urine albumin to creatinine ratio, supporting the role of endothelial dysfunction as the underlying mechanism of such deterioration.


1Department

of Neurology, Tainan Sin Lau Hospital, Tainan, Taiwan; 2Institute of Clinical Pharmacy and Pharmaceutical Science, National Cheng Kung University, Tainan, Taiwan; 3Department of Neurology, National Cheng Kung University Hospital, Tainan, Taiwan

Background: Antiepileptic drugs (AEDs) with highly inducing enzyme activity may produce metabolic abnormalities and increase cardiovascular risk. The objective of this study was to evaluate the risk of acute ischemic stroke (AIS) and myocardial infarction (AMI) in adult patients with epilepsy who newly initiate AEDs that highly induce cytochrome P450 activity (EI-AEDs) compared with those who initiate other AEDs. Methods: Consecutive patients were retrieved from the Taiwan’s National Health Insurance Research Database who had epilepsy and initiated AEDs between 2005 and 2010. A baseline period of 6 months was used to ensure no prior exposure of any AEDs and no episodes of AIS or AMI. Patients were divided into cohorts of EI-AEDs or other AEDs. We explored the incidence rate (per 1000 person-year) of combined cardiovascular (CV) events, AIS, and AMI in each cohort. A 1:1 propensity score (PS)-matched analysis was used to adjust potential confounding by indication. Cox-proportional hazard models were used to determine the odds ratios (ORs) and 95% confidence intervals (CIs). Results: For the 732,180 unmatched patients, the incidences of combined CV events were 16.2 and 6.3 per 1,000 person-years in cohorts of EI-AEDs and other AEDs. For the 492,294 patients after 1:1 PS-matching, the incidences of combined CV events were 10.3 and 5.1 per 1,000 person-years in cohorts of EI-AEDs and other AEDs. The OR of EI-AEDs for combined CV events was 1.95 (95% CI: 1.81–2.10) in the unmatched cohorts and 1.87 (95% CI: 1.71–2.04) in the PS-matched cohorts. For the PS-matched cohorts, the magnitude of increase for AIS among initiators of EIAEDs (OR: 1.93; 95% CI: 1.76–2.12) was higher than that of increase for AMI (OR: 1.56; 95% CI: 1.25–1.94). Conclusion: EI-AEDs increased CV risk, while the different magnitude of increased risks in AIS and AMI may suggest the interaction of brain disease and drug.


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1Department

S03-O2

Cerebrovascular Occlusive Disease

Propranolol Decreases Tachycardia but Does Not Improve Postural Stability and Cerebral Blood Flow in POTS Che-Wei Su1, Chuang-Chien Chiu1,2, Shoou-Jeng Yeh3 1

Ph.D. Program of Electrical and Communications Engineering, Feng Chia University, Taiwan; 2Department of Automatic Control Engineering, Feng Chia University, Taiwan; 3Section of Neurology and Neurophysiology, Taichung Cheng-ching General Hospital, Taiwan

Background and Objectives: Postural orthostatic tachycardia syndrome (POTS) is characterized by orthostatic tachycardia in the absence of orthostatic hypotension. Patients with POTS may experience lightheadedness, dizziness and instability while standing. Previous study indicates the low-dose oral propranolol significantly attenuated tachycardia and improved symptoms in POTS. Our study showed postural stability and cerebral blood flow simultaneously decreased during standing or tilting in patients with POTS. The aim of this study is to test low-dose oral propranolol can improve postural stability and cerebral blood flow. Subject and Methods: Fourteen cases with POTS underwent this study. Supine and tilting HR, BP and CBF were recorded before and one hour after taking 10 mg propranolol orally. Postural stability was measured by Center of pressure (CoP) which were collected for 300 seconds using Wii Balance Board during standing. Results: There was a significant difference of heart rate increase during tilting after propranolol treatment (HR increase = 38.9±13.2 to 29.4±9.2; p = 0.001). CoP sway was not significantly different during standing (389.9±200.2 to 383.5±199.1 Unit; p > 0.05) and CBF was also not significantly different (CBF drop % = 29.5±10.8 to 29.5±11.0; p > 0.05). Conclusion: This indicates that the low-dose oral propranolol may attenuate tachycardia and improve some symptoms in POTS but does not improved postural stability and CBF. Further research is needed in this area, particularly concerning the mechanisms of interaction between CoP, CBF and symptoms in POTS. We would like to thank the Ministry of Science and Technology for the support and funding of this research under contract number NSC102-2221-E-035-004-MY3.

S09-O1

Apearance of Extracranial Carotid Arteries in the Patients with Moyamoya Disease Chiharu Yasuda1, Shuji Arakawa1, Noriko Hagiwara1, Yuka Kanazawa1, Takafumi Shimogawa2, Tetsuro Sayama2, Takato Morioka2 1Division

of Cerebrovascular Medicine, Japan Labour Health Welfare Organization, Kyushu Rosai Hospital, Japan; 2Division of Neurosurgery, Japan Labour Health Welfare Organization, Kyushu Rosai Hospital, Japan

Background and objectives: The champagne bottle neck sign (CBNS) is a characteristic feature of extracranial carotid arteries in moyamoya disease. We investigated whether the CBNS is related to clinical stage, clinical symptom or cerebral hemodynamics in moyamoya disease. Methods: Patients with moyamoya disease who underwent cerebral angiography, carotid US, and single photon emission computed tomography (SPECT) before surgical treatment were enrolled in this study. Internal carotid artery (ICA)/common carotid artery (CCA) diameter ratio was measured using carotid US or cerebral angiography and 50% stenosis. Results: Twenty patients were included in the study. Results showed that 75% (15 out of 20) of patients with vertebrobasilar infarctions have intracranial stenosis in MRA. Out of the 15 patients with vertebrobasilar stenosis detected by MRA, 6 of them registered high mean flow velocity on TCD. TCD showed high specificity (100%) but less sensitivity (40%) in the detection of vertebrobasilar stenosis Conclusion: TCD can be suggested as a screening tool in detecting intracranial stenosis in patients with acute vertebrobasilar infarctions.


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flow on the affected side. The diagnosis of ICA hypoplasia bases on color-coded carotid duplex sonography (CCD) and further angiography, including CT angiography (CTA), MR angiography (MRA), or digital subtraction angiography (DSA). However, other vasculopathy such as dissection, Moyamoya syndrome and fibromuscular dysplasia should be distinguished from hypoplasia. Asymmetry of carotid canals implies a developmental defect of the ICA. Small carotid canal demonstrated by skull base CT provides a major diagnostic clue for ICA hypoplasia. Methods: A retrospective review of a total of 24000 carotid duplex sonographic studies was conducted at our laboratory from 2005 to 2014. ICA hypoplasia was suspected when CCD found long segmental small caliber of ICA associated with decreased flow volume in ICA but without significant intraluminal atherosclerosis or false lumen. Further clinical information was obtained from chart review and final diagnosis was confirmed by CTA, MRA, or DSA. Results: Four patients were finally diagnosed as ICA hypoplasia and each had different clinical presentations. Patient 1 suffered from a corpus callosum and intraventricular hemorrhage owing to rupture of posterior medial choroidal artery which serves as collateral flow for left ICA hypoplasia. Patient 2, who had a history of rheumatic heart disease and old cerebral infarct, was admitted for a new ischemic stroke with left hemiparesis. Image studies disclosed a left ICA hypoplasia. Patient 3 experienced two episodes of thunderclap headache. Bilateral ICA hypoplasia was noted with multiple silent lacunar infarcts. Right ICA hypoplasia was found in patient 4 during health examination. Conclusion: Although most ICA hypoplasia is asymptomatic, three out of four patients in our series are symptomatic. Recognition of this unusual abnormality is important, particularly in interpretation of CCD or angiographic results.

Poster Presentations

1. Acute Stroke Management

PA-02

Does the Presence of CTP Mismatch Predict Better Outcomes in Thrombolysis-Treated Patients? PA-01

Stroke Thrombolysis: Tissue Is More Important Than Time Andrew Bivard1, Venkatesh Krishnamurthy2, Christopher Levi2, Patrick Mcelduff2, Ferdi Miteff2, Neil Spratt2, Grant Bateman2, Geoffrey Donnan1, Stephen Davis1, Mark Parsons2

Andrew Bivard1, Venkatesh Krishnamurthy2, Christopher Levi2, Patrick Mcelduff2, Ferdi Miteff2, Neil Spratt2, Grant Bateman2, Geoffrey Donnan1, Stephen Davis1, Mark Parsons2 1

Melbourne Brain Centre, Florey Neuroscience Institute, University of Melbourne, Australia; 2Departments of Neurology, John Hunter Hospital, University of Newcastle, Australia

1

Background and Aim: Non-contrast CT (NCCT) provides minimal information on tissue and vascular pathophysiology in hyperacute stroke. Whether advanced brain imaging criteria, such as the presence and extent of irreversible and reversible ischemia, and collateral status, are more important to outcome than clinical factors, is unknown. Methods: We prospectively collected baseline, 24 hour, and day 90 clinical and imaging data from acute ischemic stroke patients being assessed for acute thrombolytic therapy at a centre where multimodal CT (NCCT, perfusion CT, and CT angiography) is used routinely as part of the decision-making process for thrombolysis. Results: Over 5 years data was collected from 646 patients with sub-4.5 hour ischemic stroke assessed by ‘standard clinical criteria’ as being potentially thrombolysis eligible. IV thrombolysis was administered to 376 patients, with 268 excluded based on CTP (small (2). Secondly, we applied specific study mismatch criteria including the EXTEND criteria (acute infarct core 1.2, absolute MM >10 mL); and DEFUSE2 criteria (acute infarct core 1.8, absolute MM >15 mL, Tmax 10 s 1 (OR mRS 0-1 1.682, mRS 0-2 1.776 and mRS 5-6 1.404), MM >1.5 (OR mRS 0-1 1.771, mRS 0-2 1.86 and mRS 5-6 1.287), and MM >2 (OR mRS 0-1 1.663, mRS 0-2 1.586 and mRS 5-6 0.235, p = 0.137). Patients who met the EXTEND criteria (72% of 378) had improved outcomes (mRS 0-1 OR 3.481, mRS 0-2 was 2.241 and mRS 5-6 0.764, p < 0.001). Patients who met the DEFUSE criteria (74% of 378) showed better outcomes (mRS 0-1 was 9.11, mRS 0-2 was 3.84 and mRS 5-6 0.532, p < 0.001). Discussion: Patients who fulfilled the specific MM selection criteria had much better outcomes with IV thrombolysis than those who did not. However the ratio of mismatch tissue in isolation did not explain the benefit of MM selection suggesting that other factors (e.g. volumes of infarct core and tissue with severely delayed perfusion) are more important.

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PA-03

PA-04

Better Stroke Outcomes Despite Worse Baseline Stroke Severity with Combined Clinical and CTP Assessment

Intravenous Thrombolysis Is Beneficial for Stroke Patients with Renal Dysfunction

Bivard1,

Krishnamurthy2,

Andrew Venkatesh Christopher Levi2, Patrick Mcelduff2, Ferdi Miteff2, Neil Spratt2, Grant Bateman2, Geoffrey Donnan1, Stephen Davis1, Mark Parsons2 1


Background: Stroke mortality rates are increasingly applied as hospital performance measures, however, the use of such data to compare stroke centres is misleading if stroke severity and case selection methods for thrombolysis are not considered. Methods: We prospectively studied 378 ischaemic stroke patients who were given intravenous rtPA at the John Hunter Hospital (JHH) using combined clinical and multimodal CT selection, and compared their outcomes to the Australian SITS registry with 545 patients given rtPA according to standard guidelines. We compared mortality rate, as well as the rates of excellent, and poor patient outcome at 3 months (mRS 0-1 and 5-6) with rtPA and major neurological improvement (MNI, NIHSS decrease >7 at 24 hours). We also compared the distribution of the acute NIHSS scores in the two datasets. Results: The JHH median Onset/door-to-needle time was 171/50 min and SITS 142/78 min. The median NIHSS of JHH rtPA patients was 15 and for SITS was 13 (p < 0.001). Only 20% of JHH patients were NIHSS 19 was associated with 60% 3 month mortality. Mortality at 3 months was lower for JHH (15.8%), compared to the SITS data of 18.7%. JHH patients had a higher rate of MNI (34%) compared to SITS (26%, p < 0.001). JHH patients were more likely to achieve excellent outcome (40% vs. SITS 35%, OR 1.23) with lower rates of poor outcome (25% vs. SITS 30%, OR 0.79). Discussion: Access to detailed information on baseline stroke severity and clinical outcome allows valid comparisons. Despite higher baseline stroke severity and later onset to treatment time, JHH rtPA treated patients had higher excellent outcomes and lower mortality.

Cheng-Yang Hsieh1,2, Huey-Juan Lin3, Sheng-Feng Sung4, Han-Chieh Hsieh5, Chih-Hung Chen5 1

Department of Neurology, Tainan Sin Lau Hospital, Tainan, Taiwan; 2Institute of Clinical Pharmacy and Pharmaceutical Science, National Cheng Kung University, Tainan, Taiwan; 3 Department of Neurology, Chi-mei Medical Center, Tainan, Taiwan; 4Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-yi Christian Hospital, Chia-yi City, Taiwan; 5Department of Neurology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Background: Renal dysfunction is a common comorbidity of acute ischemic stroke patients and may complicate intravenous thrombolysis (IVT). However, effects of IVT have not been accessed in Asian stroke patients with renal dysfunction using patients without IVT as comparator. We aimed to compare outcomes between those with and without IVT in Taiwanese stroke patients with renal dysfunction. Methods: Consecutive stroke patients with renal dysfunction and admitted within 4.5 hours of onset were recruited. Renal dysfunction was defined as estimated glomerular filtration rate (GFR) 0.5 mg/dl if the base-line value is 1 mg/dl if the base-line value is >2 mg/dl. Results: The 14 patients (14%) were diagnosed as mannitol induced ARI. From mannitol use to ARI development, median hospital days are 5 (range 3–9). The patients’ groups did not showed significant differences in demographics, neurological state, past history related with stroke, baseline renal function, and baseline osmolality. Additionally, treatment-related risks for ARI (total mannitol dosage, maximum daily dosage) also did not differ between the two groups. But, glucose level before use of mannitol and peak osmolarity during mannitol treatment were associated with ARI in univariate analysis. In logistic regression analysis with suspected factors (p value 60 minutes group (44.9±27.9 vs. 70.9±41.2 minutes, p = 0.05). Conclusions: Our study result revealed that benefit to improve DTN within 60 minutes for acute ischemic stroke patients could shorten days of hospitalization and reduce medical costs. On the other hand, avoiding in-hospital delay was more important for early iv-tPA thromboytic therapy.

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Minimizing Time To Thrombolysis: Multimodal Strategy in the Successful Implementation of a ‘Code Stroke’ Gar-Ling Lai1, Min-Jung Huang2, Hui-Hsun Chiang2, Wei-Chen Chang2, Shu-Yuan Liu2, Ming-Shiou Wang2, Chun-Hung Chen2 1

Division of Performance Management, Kaohsiung Medical University Hospital, Taiwan; 2Department of Neurology, Kaohsiung Medical University Hospital, Taiwan

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Background and Objectives: Time to thrombolytic therapy is a critical determinant of favorable outcomes in acute isch-

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Serum Pentosidine, an Advanced Glycation End Product, Indicates Progressing Stroke with Small Vessels Occlusion Toshiki Ikeda1, Keisuke Maruyama2, Ririko Takeda1, Yu-ichiro Kikkawa1, Goji Fushihara1, Yohei Yamaguchi1, Ryu Ueno1, Suguru Yokosako1, Shunsuke Ikeda1, Tomomichi Kayahara1, Hiroki Kurita1 1 Department of Cerebrovascular Surgery, International Medical Center, Saitama Medical University, Japan; 2 Department of Neurosurgery, Kyorin University Faculty of Medicine, Japan

Background: Despite the similar presentation in acute phase of ischemic stroke, patients with branch atheromatous disease (BAD) are more likely to show progressive neurologic deterioration compared to lacunar infarction (LI). The authors investigated the relationship between serum pentosidine, one of the advanced glycation end product (AGEs), and BAD. Methods: Serum pentosidine levels were measured in 39 patients with small vessels occlusion (BAD: n = 25 and LI: n = 14)


at initial hospitalization as well as other risk factors of stroke. BAD was defined as an intracerebral lesion of ≥15 mm in diameter and more than 3 slices or a lesion extending to the surface of the pontine base observed on diffusion-weighted magnetic resonance imaging, and a >2-point increase in the National Institutes of Health Stroke Scale within 48 hours of stroke onset. Outcome of patients were assessed by modified Rankin Scale score (mRS) 30 days after the onset. Univariate and multivariate logistic regression analyses were performed to analyze the factors associated with BAD. Results: Serum pentosidine in BAD group was significantly higher than LI group (BAD: 0.08±0.08 μg/ml, LI: 0.04±0.03 μg/ ml). In univariate analysis, BAD was significantly related to the high serum pentosidine level (p = 0.01), and absence of dyslipidemia (p = 0.04). Multivariate logistic regression analyses showed that high level of serum pentosidine was the only independent risk factor for BAD (p = 0.03). Conclusions: High serum level of pentosidine in patients with acute stage of stroke with small vessel occlusion indicates high risk of progressing neurological deterioration. This new biomarker provides precise information in differentiation between BAD and LI.

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Clinical Evaluation of Intravenous rt-PA Therapy for Penetrating Arterial Infarction Ryuta Morihara, Yoshiaki Takahashi, Hisashi Narai, Yasuhiro Manabe Department of Neurology, National Hospital Organization Okayama Medical Center, Japan

Background and Objectives: A recombinant tissue plasminogen activator (rt-PA), alteplase, was approved for patients with acute ischemic stroke within 4.5 h of onset in Japan at a dose of 0.6 mg/kg. The aim was to assess efficacy of alteplase for penetrating arterial infarction. Methods: Analyses were carried out in 18 patients of penetrating arterial infarction among 104 consecutive patients who admitted to our hospital received intravenous rt-PA from October 2005 to July 2013. Clinical backgrounds and outcomes were investigated. Results: The breakdown of the 18 patients was 14 males and 4 females, and the average age was 65 years. Of these patients, 12 had supratentorial infarction, 6 had infratentorial infarciton, and there was no hemorrhagic infarction. We assessed the prognosis by mRS at 3 months from onset. mRS = 0-2 were difined as good and mRS = 3-6 were difined as poor. Patients with poor outcome (n = 5, average 70 years, 3 males) showed significantly higher score of NIHSS on admission, 24 hours and 7 days after admission (P < 0.05) than patients with good outcome (n = 13, average 63 years, 11 males) and showed larger infarction volume. Conclusion: These data suggest that higher score of NIHSS on admission, 24 hours and 7 days after admission could be poor prognostic factors in intravenous rt-PA therapy for penetrating arterial infarction.


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emic stroke patients. Therefore, a coordinated multidisciplinary acute stroke team will likely avoid delays in intravenous tissue plasminogen activator (IV-tPA) administration. The aim of our study was to investigate the quality of our ‘code stroke’ protocol and its impact on door-to-needle (DTN) time, onset-to-needle (OTN) time, and clinical outcome. Methods: We developed a streamlined code stroke system, such as the computerized physician order entry (CPOE) system, 24/7 availability of neurologist, point-of-care laboratory testing, radiologist brain imaging interpretation, and video-assisted therapeutic risk communication. And we discuss each acute stroke patient in stroke meeting every month. During a period of 3 years (2011~2013), we included acute ischemic patients treat with IVtPA and compared data before and after implementation of a code stroke. Data collected were demographics, tPA dosage, time points (stroke symptom onset, presentation to ED, neuroimaging and thrombolysis), clinical outcome (90th days modified Rankin Scale (mRS), change of National Institute of Health Stroke Scale (NIHSS) at discharge, length of admission (LOA), intracerebral hemorrhage and death during admission). Results: We enrolled 13 ‘pre-code stroke’ thrombolysed patients (2011) and 40 ‘code stroke’ thrombolysed patients (2012~2013). There were no significant difference in demographics data, tPA dosage, and clinical outcome. The DTN and OTN were reduced annually, from 87.8±17.5 and 141.1±27 minutes in 2011, to 53.6±20 and 127.4±39.6 minutes in 2012, further 51±27.7 and 107.8±37.8 minutes in 2013. The IV-tPA thrombolytic rate increased from 1.93-fold (1.49% vs. 2.87%) to 2.21-fold (1.49% vs. 3.3%). Conclusions: Our clinical data revealed that standard streamlined ‘code stroke’ system rapid access protocol decreased door-to-needle and door-to-onset time and possibly contributed to the increased iv-tPA usage. On the other hand, persistent and effective supervision were necessary, in order to maintain the system in good working.

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Daily Blood Glucose Fluctuation and Neurological Outcome in Acute Ischemic Stroke Patients with Diabetes Mellitus

Factors Influencing Outcome of Patients with Intravenous Thrombolytic Therapy for Acute Ischemic Stroke

Satoshi Kubo1, Naohisa Hosomi1, Takeshi Yoshimoto2, Shuichiro Neshige2, Takahiro Himeno2, Ryuhei Kono2, Shinichi Takeshima2, Yutaka Shimoe2, Kazuhiro Takamatsu2, Taisei Ota2, Masaru Kuriyama2, Masayasu Matsumoto1

Suparus Wangtongkum, Panpisa Nantawang, Sasitorn Sirimaharaj

Background: Although hyperglycemia in acute stroke is associated with poor stroke outcomes, it remains unclear whether blood glucose fluctuations are also associated with stroke outcomes. In this study, we examined the relationships between daily blood glucose variability and early neurological outcome in acute ischemic stroke patients with diabetes mellitus. Methods: Subjects were a total of 329 acute ischemic stroke patients (216 male, 70.9±9.6 years) who were either already undergoing treatment for diabetes or had a hemoglobin A1c level of >5.8% at admission from July 2006 to June 2009. The consecutive morning fasting blood glucose (BG) levels were evaluated during 7 days from admission and described as mean and successive variation (SV). The unfavorable outcome was defined by a modified Rankin Scale score of 4 to 6 at discharge. Results: The patients with unfavorable outcome (n = 86) were older (75.7±10.5 vs. 69.2±8.6 years, p < 0.001), more frequently female (47.7% vs. 29.6%, p = 0.003), less commonly had dyslipidemia (40.7% vs. 60.9%, p = 0.001), and had higher NIHSS scores (median 9 vs. 3, p < 0.001) than those without. The mean BG levels and SV levels in patients with unfavorable outcome were higher than those in patients without (163.3±39.0 vs. 147.9±34.0 mg/ dl; p < 0.001 and 33.7±24.9 vs. 23.2±15.3 mg/dl; p < 0.001, respectively). Initial NIHSS scores and SV levels in patients with cardioembolic stroke were higher than those with other stroke subtype. After multivariate analysis with age, sex, comorbidity, stroke subtype (cardioembolic stoke or not) and initial NIHSS scores, SV levels was independently associated with unfavorable outcome (OR 1.023, 95% CI 1.004–1.042, p = 0.015), although there was no significant association between mean BG and unfavorable outcome on multivariate analysis. Conclusion: Increased blood glucose fluctuation was independently related to unfavorable outcome at discharge in acute ischemic stroke patients with diabetes mellitus.

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Objectives: To search for the factors which effect to the outcome of acute ischemic stroke patient after received intravenous rt-PA. Methods: The retrospectively reviewed the prospective stroke database for the acute ischemic stroke patient who admitted and treated with intravenous rt-PA in acute stroke unit between May 2007 to Sep 2013. The management of all stroke patients were followed the Thai clinical practice guidelines for ischemic stroke which corresponded to ASA/AHA guideline. The rt-PA was administered in the ischemic stroke patients who had the acute neurological deficit within 4.5 hr. Demographic data, atherosclerotic risk factors, blood test, NIHSS score, Barthel index, mRS on admission and discharge from hospital were recorded. The patients were classified in three groups which the first group was the favorable outcome (mRS 0-1) and second group was the independent group (mRS 2) and last group was the poor outcome or dependent (mRS 3-6). The data was analyzed the several variables using univariate and multivariate regression analyses to determine influencing factors of clinical outcomes. Results: 1,080 acute stroke patients and only 79 patients (7.3%) were received intravenous rt-PA. Twelve patients were died (15.2%) and 14 patients (17.7%) had intracranial hemorrhage (ICH) which seven patients (8.9%) had symptomatic ICH (sICH). On univariable analysis, AF and NIHSS scale, Barthel index on admission were associated with the clinical outcomes. AF was the poor prognositic factor. Low NIHSS scale and high Barthel index was the good influencing factor. And on multivariable analysis, age, NIHSS scale, Barthel index on admission and discharge of hospital and mRS on admission were the independent predictor of the clinical outcome. Increasing in age was the bad prognostic factor. Conclusion: Decreasing of age, low NIHSS scale and high Barthel index on admission and discharge from hospital and low mRS on admission were the good independent predictor of clinical outcome (mRs 0-1).


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1 Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan; 2Department of Neurology, Brain Attack Center Ota Memorial Hospital, Fukuyama, Japan

Chiangmai Neurological Hospital, Thailand

Stroke Code Improves Intravenous Thrombolysis Administration in Acute Ischemic Stroke Chih-Hao Chen1,2, Sung-Chun Tang1, Li-Kai Tsai1, Shin-Joe Yeh1, Ming-Ju Hsieh1, Kuang-Yu Huang1, Jiann-Shing Jeng1 1 2

National Taiwan University Hospital, Taiwan; Far-eastern Memorial Hospital, Taiwan

Background and Purpose: Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with ‘Stroke Code’ (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis. Methods: The study period was divided into the ‘pre-SC era’ (January 2006 to July 2010) and ‘SC era’ (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras. Results: During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of 10 (SEDAN) were associated with sICH by univariate analysis (p-value = 0.003, 75 years-old and NIHSS >10 were 1.365, 2.503, 1.107, 1.532 and 1.263 respectively. Atrial fibrillation was a predictive factor for sICH with odds ratio 2.492. Conclusions: The SEDAN score and atrial fibrillation were practical to use and predictive in Thai population. Each parameter of the SEDAN score was an independent risk factor for sICH after treatment with i.v. rt-PA.

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Beneficial Effects of Diabetes-Specific Formula on Acute Ischemic Stroke Patients Xin Zhang, Yun Xu Nanjing Drum Tower Hospital, China

Background and Aims: In this study, we investigated the effects of diabetes-specific formulas on acute ischemic stroke patients.


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carotid artery can result in disastrous outcome. But we also observed patients with ipsilateral internal carotid artery occlusion had only minor symptoms. Therefore, it seems that revasculization of the occluded internal carotid artery in patients with some collateral circulation is feasible and safe. Materials and Methods: From May 2013 to February 2014, 16 patients presented with acute internal carotid artery occlusion were screened and 7 of them were treated with mechanical thrombolysis or carotid stenting. Results: A total of 9 patients with ICA occlusion but not treated were because no adequate collateral flow. The 9 patients were all dead in a few days. The 7 patients who were all treated with penumbra aspiration system. Two of them were also treated with carotid stenting because of carotid stenosis. One patient died after failing to recanalize the ICA. Four patients can achiever favorable outcome of mRS 0-2. The other two patients were dependent with mRS 3-4. Conclusion: Through highly selected criteria such as brain CTA or CT perfusion study, some patients with suboptimal collateral flow can benefit a lot from mechanical thrombolytic therapy.

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Tirofiban Injection after Solitaire Stent Deployment as Rescue Technique in Intra-Arterial Thrombectomy: Single Center Experience Eung Kim, Jung Seo Inje University, Paik Hospital, Neurology, Korea

Background: Mechanical thrombectomy using solitaire stent (ev3 Inc, Irvine, CA, USA) has been introduced effective method in acute ischemic stroke. However, there were no consensuses on treatment strategies after the failure of the thrombectomy using solitaire stent. We described experiences about tirofiban injection after solitaire stent deployment as a rescue therapy after the failure of thrombectomy. Material and Method: Data on 11 patients treated with mechanical thrombectomy using solitaire stent were collected, retrospectively. Solitaire stent was used as primary thrombectomy method in all 11 patients. If more two times thrombectomy with solitaire stent failed, we performed the tirofiban injection after solitaire stent deployment as rescue method. Result: Median age and initial NIHSS was 68 years (range, 50–87) and 14 (range, 6–20). Female was 4 (36.3%). Mean time of FAT was 78.5 minutes. The vessel occlusions were 8 cases in


the middle cerebral artery, 1 in distal internal carotid artery, and 2 in basilar artery. Successful recanalization (TICI grade 2b and 3) using rescue method was achieved in 9 (81.8%) of all 11 patients. In two patients with no successful recanalization after rescue method, angioplasty with stent insertion was performed and successful recanalization was achieved in all 2 patients. Periprocedural complications occurred in 3 patients (distal embolization, n = 2; wire perforation, n = 1). Mortality occurred in one patient. Eight patients experienced the neurological improvement. Conclusion: We suggest that tirofiban injection after solitaire stent deployment may be effective and safe for successful recanalization after the failure of thrombectomy using solitaire stent in acute ischemic stroke.

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Impact of Weight-Change on Clinical Outcomes in Acute Ischemic Stroke Yerim Kim, Seunguk Jung, Chi Kyung Kim, Sang-Bae Ko, Seung-Hoon Lee, Byung-Woo Yoon Seoul National Univsersity Hospital, Korea

Introduction: Although there are some previous reports that mild obesity has been shown better prognosis in stroke patients, little is known about the impact of weight-change during acute ischemic stroke (IS) on the clinical outcomes. Aims: We sought to investigate the association between weight-changes and clinical short-term outcomes in IS patients. Methods: A total of 684 patients from SNUH with IS were enrolled from Mar 2010 through May 2013. Weights were measured at admission and discharge from department of neurology. Weight-change was predefined as weight-gain or weight-loss from baseline of >0.05 kg per baseline BMI-unit. Patients were divided into five groups with regard to weight-change: pronounced (>0.1 kg/baseline BMI-unit), moderate (≥0.05–0.1 kg/baseline BMI-unit), and stable group. In addition, we evaluated the clinical outcomes using modified Rankin Scale (mRS) at 3 months after stroke onset. Results: Among the 684 patients, a total of 429 patients (62.8%) were included in the stable weight-change group. Patients with weight-changes were more likely to have poor functional outcomes. We dichotomized 3-month mRS into favorable and unfavorable (3-month mRS 0-2 vs. 3-6) outcomes. After categorizing all patients into the 2 levels of initial stroke severity (NIHSS 0-3, and ≥4), the pronounced weight-loss group had a higher risk of having unfavorable outcomes (OR 2.36; 95% CI 1.03–5.41) in level of NIHSS at admission ≥4 compared to the stable weightchange group. Conclusions: In our study, patients with pronounced weightloss were associated with unfavorable short-term outcomes. Therefore, initial fluid or nutritional support should be considered when managing acute stroke patients.


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Methods: In this prospective, randomized, controlled study 104 acute ischemic patients with swallow problems were enrolled. All patients were randomly allocated into two groups, Group A (54 patients), an intervention group receiving a diabetes-specific formula (Diason, Netherlands) and Group B (51 patients), receiving a standard enteral formula. All patients were followed by 30 days. At the beginning, after 30 days, several parameters were assessed. Results: Higher percentage of CD3+ T cells and lower level of LDL was correlation with the better 30 day prognosis for acute ischemic stoke patients. After 30-day follow-up, Group A patients showed no significant nutritional changes, but an obvious decrease of triglyceride (4.58±1.11 vs. 3.81±0.96 mmol/L, P < 0.05) and low density lipoprotein (2.46±0.76 vs. 1.92±0.70 mmol/L, P < 0.05) as compared to base line. An obvious suppression of immune state was observed in severe acute ischemic patients. As following 30 days, the percentage of CD3+ T cells, CD3+CD4+ T cells and CD4+/CD8+ T cells all had significant increases in Group A after 30 days of treatment as compared to base line (P < 0.05). However, in Group B, only the CD3+CD4+ T cells subgroup had significant change after treatment. The HOMA-IR to the diabetesspecific feed was much lower at the 30 days as compared to base line (4.82±3.12 vs. 3.99±3.10, p < 0.05), but this difference was no found in standard feed group. The postprandial glucose response in diabetes-specific formula was lower as compared to base line (P < 0.05). Conclusion: A diabetes-specific formula may not only provide adequate nutrition for acute ischemic stroke patients, but may also have the effect of adjusting serum lipid, improving insulin resistance and adjusting the immune-state. A diabetes specific formula might be a suitable enteral nutrition for serve acute ischemic stroke patients.

Intravenous Thrombolysis in Acute Ischemic Stroke Patients with Thrombocytopenia Hui-Chen Su, Chih-Hung Chen Department of Neurology and Stroke Center, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

Background and Objectives: Intravenous thrombolysis in ischemic stroke is contraindicated in patients with thrombocytopenia (platelet count less than 100,000/mm3). It was supposed to increase the risk of symptomatic intracerebral hemorrhage (SICH), but there were only few reports regarding the effects of thrombolysis on stroke patient with thrombocytopenia. We report the characteristics and outcome of 3 thrombocytopenic patients treated with systemic recombinant tissue-type plasminogen activator (rtPA). Methods: We identified acute stroke patients who received intravenous rt-PA in a medical center from Sep 2006 to Apr 2014. We collected the characteristics of patients and their initial platelet blood level at emergency room. ICH was defined using ECLASS classification. Clinical outcome was determined by modified Rankin Scale (mRS). Results: There were 392 patients with acute ischemic stroke receiving rt-PA. Three (0.76%) patients were identified as thrombocytopenia (88,000/mm3, 79,000/mm3, and 56,000/mm3, respectively). One patient had ICH at day 3 of stroke. The discharge mRS was 3 in all patients. Conclusion: The ICH risk was high and outcome was poor in thrombocytopenic patients receiving rt-PA. Until more evidence was available, thrombocytopenia should be regarded as a contraindication for stroke thrombolysis.

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Ischemic Stroke Secondary to Isolated Posterior Inferior Cerebellar Artery Dissection: A Report of Ten Cases Junpei Kobayashi1, Tomoyuki Ohara1, Kazuo Minematsu1, Kazuyuki Nagatsuka2, Kazunori Toyoda1 1

Departments of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Japan; 2Departments of Neurology, National Cerebral and Cardiovascular Center, Japan

Background: The purpose of this study is to describe clinical and radiological characteristics and functional outcome in patients with ischemic stroke due to isolated dissection of the posterior inferior cerebellum artery (PICA). Methods: We retrospectively reviewed inpatients with ischemic stroke due to isolated dissection of the PICA from our stroke database between January 2004 and December 2013. Results: A total of 4,239 patients with acute ischemic stroke were admitted to our hospital during the study period. Among them, 10 (0.2%) consecutive patients (3 women; mean age,

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48.1±7.1 years) developed stroke due to isolated PICA dissection. Headache at onset was confirmed in 70%. The location of dissection was on the left side in 80%, and was the proximal portion of the PICA in 100%. PICA territory infarctions were distributed in the cerebellum (70%), lateral medulla (10%), or both of them (20%). Either one or both of pearl and string sign or intimal flap, which strongly suggested an arterial dissection, could be confirmed by magnetic resonance angiography in 80% and digital subtraction angiography in 100%. PICA dissection, which had not be identified on initial imaging, was confirmed by follow-up imaging revealing pearl and string sign in 6 cases (60%). The modified Rankin scale score at discharge was 0 in 6 patients and 1 in the other. In the follow-up period (median, 1.5 years; interquartile range 0.5–6.3), there was no recurrent ischemic or hemorrhagic stroke event. Conclusions: Stroke patients with PICA dissection were predominant in middle-aged men, having headache at onset, and usually showed favorable functional outcome. The diagnosis of PICA dissection is sometimes difficult, and requires close and repeated morphological evaluation. We should carefully identify PICA dissection as a possible cause of PICA territory infarction.

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Intravenous Thrombolysis in Acute Ischemic Stroke after Recent Major Surgery: A Case Report Weipin Hong1, Chih-Hung Chen2 1

Department of Neurology, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan; 2Department of Neurology, National Cheng Kung University, College of Medicine, Tainan, Taiwan

Background: Intravenous tissue plasminogen activator (IV t-PA) is a standard therapy for acute ischemic stroke within 3 hours of onset. There are some relative contra-indications for IV t-PA and one of which was ‘major surgery or serious trauma within recent 14 days’. However, there is no clear definition about major surgery. We introduce a patient who received IV t-PA 8 hours after recto-sigmoid colon surgery without wound bleeding. Case Presentation: A 60-year-old woman was admitted for Hartmann’s procedure (resection of recto-sigmoid colon with creation of a colostomy) due to rectal tumor. Eight hours after operation, she complained about acute onset of slurred speech and right hemiparesis with NIHSS 08. After discussion with surgeon and family, we decided to use IV t-PA in considering benefits over the risk of bleeding. Her dysarthria was improved later and right hemiparesis was improved transiently but deteriorated after 24 hours of t-PA injection. During hospitalization there was no intracranial or extracranial bleeding under close observation. She was transferred to post-acute stroke care for enhanced rehabilitation program on 19 days after operation with mRS 4. Conclusion: For acute ischemic stroke after certain major surgery, IV t-PA may be safe under close observation for bleeding events.


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The 8-Year Experience of Intravenous Thrombolytic Therapy for Acute Ischemic Stroke in a Medical Center Ya-Ju Lin1,2, Helen Po1, Chao-Liang Chou1,2, Yi-Min Chen1, Lu-An Chen1,2 1

Department of Neurology, Mackay Memorial Hospital, Taiwan; 2Mackay Medical College, Taiwan

Background and Objective: Intravenous thrombolytic therapy with tissue plasminogen activator (tPA) has been widely recommended as a standard treatment for acute ischemic stroke (AIS) in most clinical practice guidelines and has been proven in Taiwan since 2004 but still few patients received IV tPA. This study was to report our 8-year experience in the treatment of consecutive patients who had an ischemic stroke. Methods: All consecutive patients attended at the emergency department within 2 hours of symptoms onset from Jul 01, 2005 to Jun 30, 2013 were prospectively registered. All eligible patients were treated with IV tPA followed the NINDS protocol. Clinical demographics, time to treatment, NIHSS and neuroimaging were recorded by our acute stroke team. The 3-month functional outcome was described by modified Ranking scale (MRS). Results: A total of 207 patients were treated in the study period. Their mean age was 65±11.8 years; 57.5% were male. This represented 3.83% of all AIS patients admitted at our hospital (over the first 2 years, only 1.27% of all AIS patients but increased to be 7.17% within the final 2 years). The mean NIHSS score was 14±6, mean door-to-needle time was 75±27 minutes and onset-toneedle time was 123±36 minutes. 44% of patients had favorable outcome (MRS ≦2), mortality was 7.7% and 9.2% of symptomatic Intracranial hemorrhage (ICH). Conclusion: Considerably better functional outcomes were observed after IV tPA therapy without increasing symptomatic ICH. It could be given in more eligible AIS patients after better education of treating team and public awareness.

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Effect of Prior Antiplatelet Therapy on the Functional Outcome in Ischemic Stroke Patients after Thrombolysis Seunguk Jung, Chi-Kyung Kim, Yerim Kim, Sang-Bae Ko, Seung-Hoon Lee, Byung-Woo Yoon Department of Neurology, Seoul National University Hospital, Korea

Background and Purpose: There is some uncertainty whether prior use of antiplatelet (AP) drugs affects functional outcome in patients with ischemic stroke after intravenous thrombolysis. Some previous reports showed a slight but significant increase in symptomatic ICH, but no different functional outcomes in patients with prior AP therapy. But, other reports concluded the prior AP therapy was associated with a good functional outcome. The aim of this study was to estimate the effect of


prior AP therapy on functional outcome in patients with acute ischemic stroke. Background: We reviewed consecutive series of 233 patients with acute ischemic stroke who were received intravenous thrombolysis between January 2003 and April 2013. We excluded patients with oral anticoagulants, two or more antiplatelet drugs, unavailable medication history and mRS score at discharge. We used an end-point analytic technique to evaluate the association between prior AP therapy and functional outcomes: dichotomized analysis for ‘functional dependency’ (a discharge mRS score ≥3). For the multivariate analyses, we used the logistic regression models. Results: Of the 233 patients who received intravenous thrombolysis, 67 (28.7%) were on single AP therapy at stroke onset. Forty of the 67 patients (59.7%) in single AP group and 80 of the 166 patients (48.5%) in no AP group were functionally independent at discharge (p = 0.12). In the multivariate analyses, prior single AP therapy was not significantly associated with a favorable outcome at discharge (adjusted OR, 0.62; 95% CI, 0.28 to 1.35). In the subgroup analysis, a significant association between the prior AP therapy and favorable outcome was observed in the patients with cardioembolic stroke (adjusted OR, 0.34; 95% CI, 0.12 to 0.96). Conclusion: In this study, we demonstrated the beneficial effects of the prior AP on functional outcome in patients with cardioembolic stroke. However, we failed to show its beneficial effects in overall stroke patients.

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Impact of Hemoglobin Levels on the Functional Outcome in Acute Ischemic Stroke after Intravenous Thrombolysis Seunguk Jung, Chi-Kyung Kim, Yerim Kim, Sang-Bae Ko, Seung-Hoon Lee, Byung-Woo Yoon Department of Neurology, Seoul National University Hospital, Korea

Background and Purpose: Hemoglobin (Hb) levels have prognostic significance in cardiovascular diseases. However, Hb level has not been investigated as a prognostic factor after thrombolysis. In this context, we assessed whether Hb levels was related to stroke outcome after intravenous thrombolysis. Methods: A consecutive series of 140 patients with acute ischemic stroke who underwent intravenous thrombolysis were enrolled from November 2002 through April 2013. Hb levels were categorized into three groups: below 13 g/dL, 13–15 g/dL, and above 15 g/dL. We used an end-point analytic technique to evaluate the association between Hb level and functional outcomes: dichotomized analysis for ‘functional dependency’ as poor outcome (a discharge modified Rankin Scale (mRS) score ≥3). Results: Of the 140 patients, 77 (55%) were functionally dependent (mRS ≥3). In the low Hb group (n = 48, 15 g/dL), 20 (71.4%) had functional dependency. Compared with the normal Hb group and after controlling


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possible confounders, the risks of poor outcome were significantly increased in the low Hb group and the high Hb group (odds ratio for low Hb group 2.84, 95% confidence interval 1.21–6.70; odds ratio for high Hb group 5.66, 95% confidence interval 1.82– 17.6). Conclusion: From our study, we concluded that low or high Hb levels were associated with poor outcome in patients with acute ischemic stroke who underwent intravenous thrombolysis.

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Factors Associated with Changes in Stroke Severity in Patients Receiving Thrombolytic Therapy Shih-Mei Hsiao1, Ming-Zu Huang2, Ching-Wei Lin1,2, Li-Chi Hsu3, Yi-Chen Tsou4 1

PA-38

Gender Differences in the Use of Intravenous rt-PA Thrombolysis Treatment for Acute Ischemic Stroke Ying-Ting Huang1, Hui-Fen Yu2, Hsiao Chu Lin2, Ya-Ju Lin1, Helen L. Po1,2, Chao-Liang Chuo1 1 Department of Neurology, Mackay Memorial Hospital, Taiwan; 2Stroke Center, Mackay Memorial Hospital, Taiwan

Background and Objectives: Women experienced worse outcome after stroke than men. But some reports showed that women would have more frequent recanalization and better recovery after IV t-PA treatment for acute stroke compared with men. To clarify the discrepancy, we evaluated gender differences in the efficacy and safety outcomes of IV t-PA using a clinical registry. Methods: Since Jul 2005 to Jun 2013, we collected baseline characteristics, efficacy and safety outcomes for all consecutive patients who received intravenous t-PA in our center. We compared demographics, clinical features, symptom-to-needle and baseline National Institutes of Health Stroke Severity score, radiological and laboratory data, stroke mechanism, and outcome between the sexes. Results: Of all 207 treated patients, 42.5% (n = 88) were female. Compared to men, women were older (68±11.4 y/o v.s. 62±11.5, p = 0.027). They were also more likely to have a past medical history of atrial fibrillation (28.5% vs. 23.2%, p = 0.000) but no difference in hypertension, diabetes, ischemic heart disease or dyslipidemia. The NIHSS score in women was higher (15±5.8 vs. 13±5.6, p = 0.012) and longer waiting time to treatment (doorto-needle time: 80±31 vs. 71±24, p = 0.021). There’s no difference in favorable outcome (MRS ≦2, male: 44.5%, female 43.0%) but higher rate of severe disability and mortality (MRS ≧5) among female patients (male: 10.9% vs. 19.3%, p = 0.048). Conclusion: Women usually seek for emergent stroke care while having more severe cerebral ischemic symptoms and may be hesitant to receive IV tPA in time. As they were older with Af, the overall outcome after thrombolytic therapy was not so good as men.

National Taipei University of Nursing and Health Sciences Graduate Institute of Nursing, Taiwan; 2National Taipei University of Nursing and Health Sciences College of Nursing, Taiwan; 3National Taipei University of Nursing and Health Sciences Graduate Institute of Long-term Care, Taiwan; 4National Yang Ming University School of Medicine, Taiwan

Background and Objectives: The purpose of this study was to investigate factors related to change of ischemic stroke severity in patients receiving thrombolytic therapy. Methods: A sample spanning five years from Feb. 2007 to Jan. 2012 was drawn from the stroke registry database of a tertiary medical center. National Institutes of Health Stroke Scale (NIHSS) was used for the assessment of stroke severity. SPSS version 14.0 was used for statistical analysis. A p value of

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