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This study investigated the effect and mechanism of electroacupuncture (EA) on the contralesional hemisphere in rats with ischemic stroke. EA of 2 Hz was applied on the contralesionally Luoque (BL8) and Tongtian (BL7) acupoints of the scalp to investigate the neurological status and mechanism in ischemia–reperfusion injury rats. The differences in the neurological deficit score and Rotarod test time between days 3 and 15 after reperfusion were significantly lower in the sham group (0.00 (−1.00, 0.00) and 3.53 (−0.39, 7.48) second, respectively) than in the EA group (−4.00 (−4.00, −3.00) and 44.80 (41.69, 54.13) second, respectively, both p < 0.001 ). The ratio of infarction volume was 0.19 ± 0.04 in the sham group greater than 0.07 ± 0.04 in the EA group ( p < 0.001 ). On day 15, in the cerebral cortex of the lesioned hemisphere, the gamma-aminobutyric acid (GABA)-A/actin ratio in the normal group (1.11 ± 0.36) was higher than that in the sham group (0.38 ± 0.07, p < 0.05 ) and similar to that in the EA group (0.69 ± 0.18, p > 0.05 ); the difference between the EA and sham groups was significant ( p < 0.05 ). EA of 2 Hz on the BL8 and BL7 acupoints on the contralesional scalp can improve motor function and also can reduce infarction volume, and this effect of EA, and that GABA-A, plays at least a partial role in ischemia–reperfusion injury rats.

Background and aim Astragalus membranaceus (AM) is a major Chinese herb used in the treatment of stroke. Astragaloside IV (AS)is a component of AM. This study investigated the effects of AM on the protein expression through proteomics analysis in ischemia-reperfusion injured Sprague Dawley rats. Experimental procedure An animal model of ischemia-reperfusion injury by occlusion of the right middle cerebral artery for 90 min followed by reperfusion for 24 h. The rats were intraperitoneally injected with AM or AS three times at 30 min, 1 day, and 2 days prior to the occlusion of the cerebral blood flow. Results Aldolase C was overexpressed in the cortex, and Dihydrolipoamide dehydrogenase and Triose-phosphate isomerase were overexpressed in the hippocampus. Conclusion Pretreatment with AM or AS can induce the overexpression of Aldolase C in the cerebral cortex and that of Dihydrolipoamide dehydrogenase and Triose-phosphate isomerase in the hippocampus, suggesting that both AM and AS may act as neuroprotectors through regulating the expression of Aldolase C, Dihydrolipoamide dehydrogenase and Triose-phosphate isomerase. However, the underlying neuroprotective mechanisms need more studies.

Aim Chronic kidney disease (CKD) is associated with unfavorable outcomes in patients with ischemic stroke. One major metabolic derangement of CKD is dyslipidemia, which can be managed by statins. This study aimed to investigate whether the association of statins with post-stroke outcomes would be affected by renal function. Methods We evaluated the association of statin therapy at discharge with 3-month outcomes according to the estimated glomerular filtration rate (eGFR) of 50,092 patients with acute ischemic stroke from the Taiwan Stroke Registry from August 2006 to May 2016. The outcomes were mortality, functional outcome as modified Rankin Scale (mRS), and recurrent ischemic stroke at 3 months after index stroke. Results Statin therapy at discharge was associated with lower risks of mortality (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.34 to 0.50) and unfavorable functional outcomes (mRS 3-5; aHR, 0.80; 95% CI, 0.76 to 0.84) in ischemic stroke patients. After stratification by eGFR, the lower risk of mortality associated with statins was limited to patients with an eGFR above 15 mL/min/1.73 m2. Using statins at discharge was correlated with a lower risk of unfavorable functional outcomes in patients with an eGFR of 60-89 mL/min/1.73 m2. Statin therapy in patients with an eGFR of 60-89 mL/min/1.73 m2 may be associated with a higher risk of recurrent ischemic stroke compared with nonusers (aHR, 1.29; 95% CI, 1.07 to 1.57). Conclusions In patients with acute ischemic stroke, the associations of statins with mortality and functional outcomes was dependent on eGFR.

Carotid intima&ndash, media thickness (IMT), plaque, and stenosis are widely used as early surrogate markers of subclinical atherosclerosis and strong predictors of future deaths and cardiovascular events. Albuminuria is an indicator of generalized endothelial dysfunction that speeds up atherosclerosis. However, previous studies reporting these associations cannot rule out the confounding effect of albuminuria. We aimed to examine the independent and joint relationships between IMT markers and 10-year mortality in community-dwelling Taiwanese adults. This work was a community-based prospective cohort study consisting of 2956 adults aged at least 30 years recruited in 2007 and followed up through 2019. Cox proportional hazard regression models were used to examine associations of these subclinical atherosclerosis markers with mortality. During an average of 9.41 years of follow up, 242 deaths occurred. The mortality rate was 8.70 per 1000 person-years. Compared with those with carotid IMT less than 1.0 mm, persons with severely increased carotid IMT (&ge, 2.0 mm) had an increased risk for death (hazard ratio (HR): 1.79, 95% confidence interval (CI): 1.07, 3.00). Compared with those without carotid plaque, persons with carotid plaque were more likely to have an increased risk for death (1.65, 1.21&ndash, 2.32). Compared with those with carotid stenosis less than 25%, persons with carotid stenosis of 25&ndash, 36% had a significant increased risk for death (1.57, 1.12&ndash, 2.22). Considering these three IMT markers along with the traditional risk factors (c-statistic: 0.85) significantly increased their predictive ability of mortality compared with any individual variable&rsquo, s predictive ability (all p-values &lt, 0.001 for comparisons of c-statistic values). Carotid IMT measures, including IMT thickness, carotid plaque, and carotid stenosis were significant independent predictors of mortality. Our study supports evidence of blood pressure-related media thickening markers to assess future mortality risks in Chinese adults of general population.

Background and aim Astragalus membranaceus (AM) is a major Chinese herb used in the treatment of stroke. Astragaloside IV (AS)is a component of AM. This study investigated the effects of AM on the protein expression through proteomics analysis in ischemia-reperfusion injured Sprague Dawley rats. Experimental procedure An animal model of ischemia-reperfusion injury by occlusion of the right middle cerebral artery for 90 min followed by reperfusion for 24 h. The rats were intraperitoneally injected with AM or AS three times at 30 min, 1 day, and 2 days prior to the occlusion of the cerebral blood flow. Results Aldolase C was overexpressed in the cortex, and Dihydrolipoamide dehydrogenase and Triose-phosphate isomerase were overexpressed in the hippocampus. Conclusion Pretreatment with AM or AS can induce the overexpression of Aldolase C in the cerebral cortex and that of Dihydrolipoamide dehydrogenase and Triose-phosphate isomerase in the hippocampus, suggesting that both AM and AS may act as neuroprotectors through regulating the expression of Aldolase C, Dihydrolipoamide dehydrogenase and Triose-phosphate isomerase. However, the underlying neuroprotective mechanisms need more studies., Graphical abstract Image 1, Highlights • Astragalus membranaceus(AM) is a famous Chinese herb for treating stroke. • This study used Proteomics analysis to investigate the protein biomarkers of brain tissue in AM and its component of Astragaloside (AS) treating ischemic stroke. • The present study found that Aldolase C in the cortex, and Dihydrolipoamide dehydrogenase and Triose- in the hippocampus were overexpression.

Background: The natural history of vertebrobasilar artery (VBA) stenosis or occlusion remains understudied. Methods: Patients with diagnosis of ischemic stroke or transient ischemic attack (TIA) who were noted to have VBA stenosis based on computed tomography or magnetic resonance imaging or catheter-based angiogram were selected from Taiwan Stroke Registry. Cox proportional hazards model was used to determine the hazards ratio (HR) of recurrent stroke and death within 1 year of index event in various groups based on severity of VBA stenosis (none to mild: 0–49%; moderate to severe: 50–99%: occlusion: 100%) after adjusting for differences in demographic and clinical characteristics between groups at baseline evaluation. Results: None to mild or moderate to severe VBA stenosis was diagnosed in 6972 (66%) and 3,137 (29.8%) among 10,515 patients, respectively, and occlusion was identified in 406 (3.8%) patients. Comparing with patients who showed none to mild stenosis of VBA, there was a significantly higher risk of recurrent stroke (HR 1.21, 95% CI 1.01–1.45) among patients with moderate to severe VBA stenosis. There was a nonsignificantly higher risk of recurrent stroke (HR 1.49, 95% CI 0.99–2.22) and significantly higher risk of death (HR 2.21, 95% CI 1.72–2.83), among patients with VBA occlusion after adjustment of potential confounders. Conclusions: VBA stenosis or occlusion was relatively prevalent among patients with TIA or ischemic stroke and associated with higher risk of recurrent stroke and death in patients with ischemic stroke or TIA who had large artery atherosclerosis.

Background and Purpose— The observation that smokers with stroke could have better outcome than nonsmokers led to the term “smoking paradox.” The controversy of such a complex claim has not been fully settled, even though different case mix was noted. Analyses were conducted on 2 independent data sets to evaluate and determine whether such a paradox truly exists. Methods— Taiwan Stroke Registry with 88 925 stroke cases, and MJ cohort with 541 047 adults participating in a medical screening program with 1630 stroke deaths developed during 15 years of follow-up (1994–2008). Primary outcome for stroke registry was functional independence at 3 months by modified Rankin Scale score ≤2, for individuals classified by National Institutes of Health Stroke Scale score at admission. For MJ cohort, mortality risk by smoking status or by stroke history was assessed by hazard ratio. Results— A >11-year age difference in stroke incidence was found between smokers and nonsmokers, with a median age of 60.2 years for current smokers and 71.6 years for nonsmokers. For smokers, favorable outcome in mortality and in functional assessment in 3 months with modified Rankin Scale score ≤2 stratified by the National Institutes of Health Stroke Scale score was present but disappeared when age and sex were matched. Smokers without stroke history had a ≈2-fold increase in stroke deaths (2.05 for ischemic stroke and 1.53 for hemorrhagic stroke) but smokers with stroke history, 7.83-fold increase, overshadowing smoking risk. Quitting smoking at earlier age reversed or improved outcome. Conclusions— “The more you smoke, the earlier you stroke, and the longer sufferings you have to cope.” Smokers had 2-fold mortality from stroke but endured stroke disability 11 years longer. Quitting early reduced or reversed the harms.

Background and aims This study investigated risks of short-term (1 and 3 months) and long-term (1-year) recurrent stroke associated with glomerular filtration rate (eGFR) in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we identified 45,876 acute ischemic stroke patients from April 2006 to April 2014 and classified them into 4 groups based on the eGFR at admission: ≥ 90, 60–89, 30–59, and Results Both the risks of short-term and long-term recurrent stroke increased as the eGFR levels declined. The 1-month recurrent incidence rates increased steadily from 0.54 to 0.59, 0.84 and 0.89 per 1000 person-days, as the eGFR declined from ≥90 to 60–89, 30–59, and Conclusions There is an independent graded association between an increased risk of recurrent stroke and declining eGFR levels in patients with acute ischemic stroke.

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Background: Stroke is one of the leading causes of mortality and neurologic deficits. Management measures to improve neurologic outcomes are in great need. Our previous intervention trial in elderly subjects successfully used salt as a carrier for potassium, demonstrating a 41% reduction in cardiovascular mortality by switching to potassium-enriched salt. Dietary magnesium has been associated with lowered diabetes and/or stroke risk in humans and with neuroprotection in animals.Objective: Because a large proportion of Taiwanese individuals are in marginal deficiency states for potassium and for magnesium and salt is a good carrier for minerals, it is justifiable to study whether further enriching salt with magnesium at an amount near the Dietary Reference Intake (DRI) amount may provide additional benefit for stroke recovery.Design: This was a double-blind, randomized controlled trial comprising 291 discharged stroke patients with modified Rankin scale (mRS) ≤4. There were 3 arms: 1) regular salt (Na salt) (n = 99), 2) potassium-enriched salt (K salt) (n = 97), and 3) potassium- and magnesium-enriched salt (K/Mg salt) (n = 95). The NIH Stroke Scale (NIHSS), Barthel Index (BI), and mRS were evaluated at discharge, at 3 mo, and at 6 mo. A good neurologic performance was defined by NIHSS = 0, BI = 100, and mRS ≤1.Results: After the 6-mo intervention, the proportion of patients with good neurologic performance increased in a greater magnitude in the K/Mg salt group than in the K salt group and the Na salt group, in that order. The K/Mg salt group had a significantly increased OR (2.25; 95% CI: 1.09, 4.67) of achieving good neurologic performance compared with the Na salt group. But the effect of K salt alone (OR: 1.58; 95% CI: 0.77, 3.22) was not significant.Conclusions: This study suggests that providing the DRI amount of magnesium and potassium together long term is beneficial for stroke patient recovery from neurologic deficits. This trial was registered at clinicaltrials.gov as NCT02910427.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Additional file 1: Figure S1. Time points of the data collection for the Taichung Community Health Study (TCHS), Taichung Community Health Study-Elder (TCHS-E), and Family Study of TCHS and TCHS-E. Table S1. Multivariate analysis of carotid intima-media thickness for serum cystain C, albumin-to-creatinine ration, and estimated glomerular filtration rate along with traditional risk factors. Table S2. Multivariate analysis of carotid intima-media thickness for serum cystain C, albumin-to-creatinine ration, and serum creatinine along with traditional risk factors.

L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid β (Aβ) stimulates platelet aggregation, we studied whether L5 and Aβ function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Aβ, and platelet LOX-1 expression were significantly higher in acute ischemic stroke patients than in controls without metabolic syndrome (P < .01). In mice subjected to focal cerebral ischemia, L5 treatment resulted in larger infarction volumes than did phosphate-buffered saline treatment. Deficiency or neutralizing of LOX-1 reduced infarct volume up to threefold after focal cerebral ischemia in mice, illustrating the importance of LOX-1 in stroke injury. In human platelets, L5 but not L1 (the least electronegative LDL subfraction) induced Aβ release via IκB kinase 2 (IKK2). Furthermore, L5+Aβ synergistically induced glycoprotein IIb/IIIa receptor activation; phosphorylation of IKK2, IκBα, p65, and c-Jun N-terminal kinase 1; and platelet aggregation. These effects were blocked by inhibiting IKK2, LOX-1, or nuclear factor-κB (NF-κB). Injecting L5+Aβ shortened tail-bleeding time by 50% (n = 12; P < .05 vs L1-injected mice), which was prevented by the IKK2 inhibitor. Our findings suggest that, through LOX-1, atherogenic L5 potentiates Aβ-mediated platelet activation, platelet aggregation, and hemostasis via IKK2/NF-κB signaling. L5 elevation may be a risk factor for cerebral atherothrombosis, and downregulating LOX-1 and inhibiting IKK2 may be novel antithrombotic strategies.

Background Clopidogrel was thought to be superior to aspirin for secondary prevention of vascular diseases in clinical trials. In this study we assessed the safety and efficacy of clopidogrel versus aspirin in real‐world practice by using the Taiwan Stroke Registry. Methods and Results Patients with ischemic stroke (2006–2016) on aspirin or clopidogrel for secondary stroke prevention were identified in the Taiwan Stroke Registry. Stroke recurrence and mortality rates in patients receiving aspirin (N=34 679) were compared with those receiving clopidogrel (N=7611) during a 12‐month follow‐up period. Propensity score matching and conditional Cox proportional hazards regression model were applied to control confounding factors with 6443 patients in each group. After propensity score matching, stroke recurrence rates were comparable between groups, with 223 patients in the aspirin (3.46%) and 244 in the clopidogrel group (3.79%) (hazard ratio=1.13, 95% confidence interval=0.89–1.43, P =0.311). However, the mortality rate was significantly higher in the clopidogrel group (362 patients, 5.62%) than in the aspirin group (302 patients, 4.69%) (hazard ratio=1.30, 95% confidence interval=1.07–1.58, P =0.008). Results were consistent before and after propensity score matching. Conclusions Clopidogrel was as effective as aspirin for prevention of recurrent stroke in real‐world practice. However, the mortality rate was significantly higher in the clopidogrel than in the aspirin group.

Background: The risk of recurrent stroke in patients with ischemic stroke with vertebral/basilar artery stenosis remains to be systematically studied. Methods: We analyzed data from Taiwan Stroke Registry (TSR), with stroke registries provided by 59 hospitals. Patients who had diagnosis of ischemic stroke and were categorized into the “large artery atherosclerosis” group by TOAST who underwent CTA, MRA, or catheter- based angiography were identified for the present study. The patients were divided into 3 groups based on the extent of vertebral (VA) and/or basilar artery (BA) stenosis as follows: 0-49%, 50-99%, and 100% (total occlusion). Cox proportional hazards model was used to determine the hazard ratios (HRs) of recurrent stroke within 1 year of index event after adjusting for all relevant risk factors by univariable Cox model. Results: In the TSR data base, 84,831patients were in the ischemic stroke group. Based on TOAST, 20,220 patients were in the large-artery atherosclerosis group. Among these patients, a total of 10,515 were of age 18 or greater who had CTA, MRA or angiographic studies that included VA/BA. There were 6,972 subjects with VA/BA stenosis in the 0-49%, 3,137 in the 50-99% and 406 in the 100% (total occlusion) groups respectively. With VA/BA stenosis in the 0-49% range as the reference, HRs of recurrent stroke in one year by multivariable modeling with adjustment of all relevant risk factors by univariable Cox model was 1. 29 (95% CI, 1.05 - 1.58, p Conclusions: Vertebral or basilar artery stenosis or occlusion was relatively prevalent among patients with ischemic stroke categorized in the large artery artherosclerosis group by TOAST with greater extent of VA/BA stenosis carrying greater risk of recurrent stroke within 1 year after stroke.

Objective: This study was to assess the 30-day and 1-year mortality associated with serum triglyceride levels on admission for patients with acute ischemic stroke using the Taiwan Stroke registry (TSR) data. Patients and methods: From the TSR database, we identified 45931 acute ischemic stroke patients from April 2006 to April 2014 and stratified them into 3 groups by the serum triglyceride level measured on admission: 200 mg/dL, those with triglyceride levels

Background Pulse pressure (PP) is related to cardiac function, arterial stiffness, fluid status, and vascular events. This study aimed to explore the prognostic role of PP upon admission in patients with acute ischemic stroke (AIS) based on a nation‐wide stroke registry. Methods and Results We evaluated the association between PP upon admission and outcomes 3 months after a stroke in patients who had an AIS registered in the Taiwan Stroke Registry, including 56 academic and community hospitals between 2006 and 2013. Three months after the stroke, unfavorable outcomes were defined using a modified Rankin scale of 3 to 6. Of 33 530 patients (female, 40.6%; mean age, 68.8±13.3 years) who had an AIS, PP upon admission had a reverse J‐curve association with an unfavorable outcome. After adjusting for clinical variables, including AIS subtypes, initial National Institutes of Health Stroke Scale, and systolic and diastolic blood pressure upon admission, a PP of P Conclusions Low PP upon admission was associated with unfavorable patient outcomes in AIS.

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Background and purpose Physical activity is associated with a reduced incidence of first-time stroke. However, few studies have examined the effect of pre-stroke physical activity on post-stroke complications and clinical outcomes. Methods A total of 39 835 cases of stroke registered in the nationwide stroke registry system of Taiwan between 2006 and 2009 were analyzed according to five levels of severity as determined by National Institutes of Health Stroke Scale score upon hospital admission. Pre-stroke physical activity was defined in the Taiwan Stroke Registry as dedicated leisure-time physical activity for at least 30 min/day for 3 days/week for more than 6 months. A Cox model was used to compare complications and outcomes between active and inactive groups. Results The active and inactive groups were similar in age distribution and stroke type distribution, but the active group had better National Institutes of Health Stroke Scale scores upon admission. The active group also had significantly fewer post-stroke complications. Active patients had lower hospital mortality and better functional outcomes upon discharge as per the modified Rankin Scale. Improved functional status in the active group was significant at 1, 3 and 6 months post-stroke. Conclusion Dedicated leisure-time physical activity for at least 30 min/day, at least three times per week for more than 6 months was associated with decreased stroke severity, fewer post-stroke complications, lower mortality and better outcomes.

Rationale It is not uncommon for patients with ischemic stroke to have peripheral arterial disease (PAD). Patients with polyvascular diseases carry greater burden of atherosclerosis and higher risks of developing vascular events and death. More effective regimens, such as dual antiplatelet agents, may be more effective for controlling progression of atherosclerosis in secondary prevention. Aim This study aims to evaluate whether cilostazol plus aspirin is more efficacious than aspirin alone for preventing progression of atherosclerosis in patients with ischemic stroke or transient ischemic attack (TIA) who also have peripheral arterial disease. Design The Safety and Efficacy of Cilostazol in Ischemic Stroke Patients with Peripheral Arterial Disease (SPAD) study is a randomized double-blinded placebo-controlled trial. Patients with previous ischemic stroke or TIA who had been taking aspirin (100 mg per day), aged 50 years or older, with PAD in the lower limbs based on ankle-brachial index (ABI) Study outcomes Patients will be evaluated at 1, 3, 6, 9 and 12 months after randomization. The primary endpoint is difference in change in ABI between groups. The secondary and tertiary endpoints are the difference between groups in change in carotid intima-media thickness (IMT) and incidence rate of major cardiovascular events, including recurrent stroke, myocardial infarction, unstable angina, other vascular events, and death; and the safety measures, including major bleeding events, hemorrhagic stroke and death of any cause. Conclusion The SPAD trial is the first study to evaluate the safety and efficacy of dual antiplatelet agents, aspirin plus cilostazol, in comparison with aspirin alone in patients with both ischemic stroke or TIA and PAD. Results from this trial will provide important information on the merit of adding cilostazol to aspirin for slowing down progression of atherosclerosis in patients with ischemic stroke and PAD.

We investigated the relationship between Chinese medicine pattern (CMP) types, their severity, and prognosis in patients (n = 187) with acute cerebral infarct (ACI). Six CMPs (wind, phlegm, fire-heat, blood stasis, qi deficiency, and yin deficiency and yang hyperactivity) were evaluated according to inspection, listening and smelling, inquiry, and palpitation. The severity and prognosis of each pattern type was determined according to the Glasgow Coma Scale (GCS), Modified Rankin Scale (MRS), National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), and Functional Independence Measure (FIM), recorded at stroke onset and 12 weeks after stroke onset. The phlegm pattern (PP) patients displayed lower GCS, BI, and FIM scales scores, and higher MRS and NIHSS scales scores, than the nonphlegm pattern (N-PP) patients at, and 12 weeks after stroke onset, suggesting the clinical severity is greater and the prognosis is worse in PP patients with ACI than in non-PP patients with ACI.

Background Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). Methods Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with 200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC 15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41-2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11-1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI)

Background and purpose Astragalus membranaceus (AM) is the first-choice herb for fatigue treatment in traditional Chinese medicine and the main herb used for stroke treatment in China and Taiwan. The purpose of this study was to evaluate the effect of AM on poststroke fatigue (PSF). Materials and methods This study was designed as a double-blind, randomized, controlled preliminary study. Sixty-four patients with PSF were assigned to treatment group (TG; 31 patients), which received oral administration of AM (2.8 g three times per day) for 28 days, and a control group (CG; 33 patients), which received a placebo. The primary outcome measures were the changes in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Brief Fatigue Index (BFI) scores Results A total of 61 patients (29 patients in the TG and 32 patients in the CG) completed the trial. The difference in BFI scores between Visit 2 and Visit 1 was –17.83±17.70 in the TG, which was greater than that in the CG (–8.03±9.95; p=0.01); additionally, the difference in BFI scores between Visit 3 and Visit 1 was –16.48±16.41 in the TG, which was also greater than that in the CG (–9.47±13.39; p=0.05). In the EORTC QLQ-C30, the difference in cognitive functioning scores between Visit 2 and Visit 1 was 14.37±13.89 in the TG, which was greater than that in the CG (3.65±19.74; p=0.02); additionally, the difference in these scores between Visit 3 and Visit 1 was 14.37±16.50 in the TG, which again was greater than that in the CG (6.25±19.74; p=0.04). The difference in social functioning scores between Visit 3 and Visit 1 was 9.77±15.12 in the TG, which was greater than that in the CG (–1.56±20.46; p=0.01). The difference in global quality of life (QOL) scores between Visit 2 and Visit 1 was 14.08±18.78 in the TG, which was also greater than that in the CG (1.56±18.14; p=0.003); moreover, the difference in these scores between Visit 3 and Visit 1 was 10.92±17.55 in the TG, and this was greater than that in the CG (1.82±15.8; p=0.05). Conclusion AM can improve BFI scores; cognitive functioning, social functioning, and global QOL scores in the EORTC QLQ-C30. Our results suggest that physicians should pay close attention to the unmet medical needs of patients with PSF. AM is helpful for treating patients with PSF; however, additional studies with a larger sample and a longer period of investigation are required.

Uncaria rhynchophylla(UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus

In this paper we propose a novel scheme able to automatically detect the intima and adventitia of both near and far walls of the common carotid artery in dynamic B-mode RF (radiofrequency) image sequences, with and without plaques. Via this automated system the lumen diameter changes along the heart cycle can be detected. Three image sequences have been tested and all results are compared to manual tracings made by two professional experts. The average errors for near and far wall detection are 0.058 mm and 0.067 mm, respectively. This system is able to analyze arterial plaques dynamically which is impossible to do manually due to the tremendous human workload involved.

Background— Stroke is a leading cause of death around the world. Improving the quality of stroke care is a global priority, despite the diverse healthcare economies across nations. The American Heart Association/American Stroke Association Get With the Guidelines-Stroke program (GWTG-Stroke) has improved the quality of stroke care in 790 US academic and community hospitals, with broad implications for the rest of the country. The generalizability of GWTG-Stroke across national and economic boundaries remains to be tested. The Taiwan Stroke Registry, with 30 599 stroke admissions between 2006 and 2008, was used to assess the applicability of GWTG-Stroke in Taiwan, which spends ≈1/10 of what the United States does in medical costs per new or recurrent stroke. Methods and Results— Taiwan Stroke Registry, sponsored by the Taiwan Department of Health, engages 39 academic and community hospitals and covers the entire country with 4 steps of quality control to ensure the reliability of entered data. Five GWTG-Stroke performance measures and 1 safety indicator are applicable to assess Taiwan Stroke Registry quality of stroke care. Demographic and outcome figures are comparable between GWTG-Stroke and Taiwan Stroke Registry. Two indicators (early and discharge antithrombotics) are close to GWTG-Stroke standards, while 3 other indicators (intravenous tissue plasminogen activator, anticoagulation for atrial fibrillation, lipid-lowering medication) and 1 safety indicator fall behind. Preliminary analysis shows that compliance with selected GWTG-Stroke guidelines is associated with better outcomes. Conclusions— Results suggest that GWTG-Stroke performance measures, with modification for ethnic factors, can become global standards across national and economic boundaries for assessing and improving quality of stroke care and outcomes. GWTG-Stroke can be incorporated into ongoing stroke registries across nations.

Paeoniflorin, a component in Paeonia lactiflora Pall, inhibits nuclear factor-κB expression in chronic hypoperfusion rat and has anti-inflammatory properties. Therefore, the aim of the present study was to investigate the effect of paeoniflorin on cerebral infarct, and the involvement of anti-inflammation. We established an animal model of cerebral infarct by occluding both the common carotid arteries and the right middle cerebral artery for 90 min, followed by reperfusion of 24 hours. The ratios of cerebral infarction area to total brain area, and neuro-deficit score were used as an index to observe the effects of paeoniflorin on cerebral infarct. ED1 (mouse anti rat CD68), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), intercellular adhesion molecular-1 (ICAM-1), myeloperoxidase (MPO) immunostaining and apoptotic cells in the cerebral infarction region also were studied. The results indicated that both pre-treatment and post-treatment with paeoniflorin reduced the ratio of cerebral infarction area; pre-treatment with paeoniflorin also reduced the neurological deficit score. The counts of ED1, IL-1β, TNF-α, ICAM-1 of microvessels and MPO immunoreactive cells and apoptotic cells were increased in the cerebral infarction region; however, these increases were reduced by Paeoniflorin pre-treatment.In conclusion, Paeoniflorin reduced cerebral infarct and neurological deficit in ischemia-reperfusion injured rats, suggesting that paeoniflorin may have a similar effect in humans and might be a suitable treatment for stroke. Paeoniflorin reduced cerebral infarct, at least in part, involves the anti-inflammatory properties.

Uncaria rhynchophylla (Miq) Jack (UR) is a traditional Chinese herb and is used for the treatment of convulsive disorders, including epilepsy. Our previous study has shown that UR, as well as its major component rhynchophylline (RH), has an anticonvulsive effect and this effect is closely related to its scavenging activities of oxygen free radicals. The purpose of the present study was to investigate the effect of (UR) on the expression of proteins using a proteomics analysis in Sprague-Dawley (SD) rats with kainic acid (KA)-induced epileptic seizures. We profiled the differentially expressed proteins on two-dimensional electrophoresis (2-DE) maps derived from the frontal cortex and hippocampus of rat brain tissue 24 hours after KA-induced epileptic seizures. The results indicated that macrophage migration inhibitory factor (MIF) and cyclophilin A were under expressed in frontal cortex by an average of 0.19- and 0.23-fold, respectively. In the frontal cortex, MIF and cyclophilin A were significantly decreased in the KA group and these decreases were confirmed by the Western blots. However, in the hippocampus, only cyclophilin A was significantly decreased in the KA group. In addition, in real-time quantitative PCR (Q-PCR), MIF and cyclophilin A gene expressions were also significantly under expressed in the frontal cortex, and only the cyclophilin A gene was also significantly under expressed in the hippocampus in the KA group. These under expressions of MIF and cyclophilin A could be overcome by the treatment of UR and RH. In conclusion, the under expressions of MIF and cyclophilin A in the frontal cortex and hippocampus in KA-treated rats, which were overcome by both UR and UH treatment, suggesting that both MIF and cyclophilin A at least partly participate in the anticonvulsive effect of UR.

SUMMARY Background: The cutoff of abdominal circumference for metabolic syndrome (MS) defined by the Bureau of Health Promotion (BHP) of Taiwan for Taiwanese (men, 90 cm; women, 80 cm) and by the International Diabetes Federation (IDF) for Japanese (men, 85 cm; women, 90 cm) differs. This study aimed to examine the impact of this difference on the prevalence of MS and the impact of an MS diagnosis on the projected risk of stroke in hypertensive Taiwanese. Methods: MS was examined in a sample of 3,472 hypertensive patients (aged 55–80 years; 1,709 women) across Taiwan. The 10-year probability of stroke estimated from the Framingham equation was compared between MS and non-MS patients. Results: The prevalence of MS using the BHP criteria was 59.2% using the BHP criteria (95% confidence interval, CI, 57.6–60.8%; men, 52.5%; women, 66.1%) and 48.9% by the IDF criteria (95% CI, 47.2–50.5%; men, 61.3%; women, 36.1%). Both criteria showed that, compared with non-MS, MS has higher predicted 10-year probability of stroke (BHP, 0.153 ± 0.115 vs. 0.133 ± 0.105; IDF, 0.159 ± 0.109 vs. 0.132 ± 0.112; both p < 0.001) because of the difference in women (BHP, 0.143 ± 0.124 vs. 0.102 ± 0.091; IDF, 0.147 ± 0.121 vs. 0.118 ± 0.110; both p < 0.001) rather than men (BHP, p = 0.21; IDF, p = 0.29). Conclusion: Both criteria demonstrate that MS is highly prevalent in elderly hypertensive patients in Taiwan. Additionally in women, but not men, the predicted probability of stroke is higher in MS than in non-MS patients. The diagnosis of MS is potentially useful for identifying elderly hypertensive females with an elevated risk of stroke in Taiwan. [International Journal of Gerontology 2009; 3(4): 233–240]

Both Moutan cortex of Paeonia suffruticosa Andrews (MC) and the root of Paeonia lactiflora Pall (PL) are important Traditional Chinese herbs used commonly to treat inflammatory and pyretic disorders. Paeonol, a common component of MC causes anti-platelet aggregation and scavenges free radicals. Therefore, the aim of the present study is to investigate the effects of Paeonol on cerebral infarct. A total of 60 male Sprague-Dawley (SD) rats were studied. An animal model of cerebral infarct was established by occluding both common carotid arteries and the right middle cerebral artery for 90 min, followed by a 24 h period of reperfusion. The percentage of cerebral infarction area to total brain area in each piece of brain tissue, and neuro-deficit score were measured. Superoxide anion was determined by the number of lucigenin-chemiluminescence (CL) counts. ED1 (mouse anti rat CD68) and interleukin-1beta (IL-1beta) immunostaining in the cerebral infarction region were also investigated for activation of microglia. The results indicated that Paeonol 15 and 20 mg/kg pretreatment and 20 mg posttreatment reduced the cerebral infarction area; Paeonol 15 and 20 mg/kg pretreatment reduced the neuro-deficit score. In addition, Paeonol 20 mg/kg pretreatment reduced the lucigenin-CL counts at 2 h period of reperfusion. The number of ED1 and IL-1beta immunoreactive cells also reduced in the cerebral infarction region; there were no significant changes in blood sugar levels. The results show that Paeonol reduced cerebral infarct and neuro-deficit in rat, suggesting Paeonol might play a similar role in reducing cerebral infarction in humans. Paeonol suppresses and scavenges superoxide anion, and inhibit microglia activation and IL-1beta in ischemia-reperfusion injured rats.

Electroacupuncture (EA) is widely used to treat disorders of the nervous system, such as stroke. The aim of the present study was to investigate the effect of EA on cerebral blood flow (CBF) in cerebral ischemic rats. We developed an animal model of cerebral ischemia (CI) by occluding the blood flow of both common carotid arteries in Sprague-Dawley (SD) rats; 2 or 15 Hz EA was applied to both Zusanli acupoints. The levels of nitric oxide (NO) in the peripheral blood and amounts of calcitonin gene-related peptide (CGRP) in the cerebral cortex and thalamus were measured. In addition, L-N (G)-nitro arginine methyl ester (L-NAME) was used to measure the changes in CBF induced by EA in rats with and without CI. The results indicated that both 2 and 15 Hz EA increase the mean CBF in rats with and without CI. However, neither 2 nor 15 Hz EA induced changes in levels of NO in peripheral blood or changes in CGRP levels in cerebral cortex and thalamus. In addition, L-NAME did not change the increase in CBF. We concluded that both 2 and 15 Hz EA at both Zusanli acupoints induced the increase of CBF in rats with and without CI. Whether the effect of EA is related to NO or CGRP will be investigated in a future study.

Acupuncture has been used widely to treat disease; however, the time course for acupuncture to have an effect remains unclear. Therefore, the aim of the present study was to investigate the time course of changes in nail fold microcirculation (NFM) induced by acupuncture stimulation (AS) at the right and left Waiguan acupoints (WAs). A total of 38 healthy female volunteers, age range from 21 to 33, were studied. We recorded NFM of the right middle finger before, and 5 min, 10 min, 15 min and 20 min after initiating AS; NFM was also recorded 5 min and 10 min after secessions of AS. Nitric oxide (NO) and endothelin-1 levels were measured from the left cubital vein, before AS and 10 min after stopping AS. The results indicated that capillary density of NFM increased 5 min after AS at the right Waiguan acupoint (WA); however, similar changes were not noted at the left WA. The capillary density decreased beginning 15 min after AS at the right and left WA. Capillary red blood cell velocity increased 5 min and 10 min after AS at the right and left WAs, but decreased 5 min and 10 min after stopping AS at the left WA. NO and endothein-1 levels were similar before AS and 10 min after stopping AS. Therefore, we suggest that a segmental effect of the spinal nerve contributes to the increasing capillary density of NFM induced by AS. The effect of acupuncture on NFM lasts about 10–15 min. The changes of balance between the sympathetic nerve activities and parasympathetic nerve activities may be induced by AS.

Background Discharge disposition planning is vital for poststroke patients. We investigated clinical factors associated with discharging patients to nursing homes, using the Taiwan Stroke Registry data collected from 39 major hospitals. Methods We randomly assigned 21,575 stroke inpatients registered from 2006 to 2008 into derivation and validation groups at a 3-to-1 ratio. We used the derivation group to develop a prediction model by measuring cumulative risk scores associated with potential predictors: age, sex, hypertension, diabetes mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types, and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing home care and odds ratio (OR) of nursing home care relative to home care by cumulative risk scores were measured for the prediction. The area under the receiver operating characteristic curve (AUROC) was used to assess the model discrimination against the validation group. Results Except for hypertension, all remaining potential predictors were significant independent predictors associated with stroke patient disposition to nursing home care after discharge from hospitals. The risk sharply increased with age and NIHSS. Patients with a cumulative risk score of 15 or more had an OR of 86.4 for the nursing home disposition. The AUROC plots showed similar areas under curves for the derivation group (.86, 95% confidence interval [CI], .85-.87) and for the validation group (.84, 95% CI, .83-.86). Conclusions The cumulative risk score is an easy-to-estimate tool for preparing stroke patients and their family for disposition on discharge.

The relationship between low estimated glomerular filtration rate (eGFR) and the outcome of ischemic stroke remains controversial, despite the close association between kidney dysfunction and atherosclerosis.This study conducted subgroup analysis using data from the prospective Taiwan Stroke Registry to investigate the relationship between eGFR at the time of admission and 6-month functional outcomes in patients with the large artery atherosclerotic (LAA) subtype of acute ischemic stroke. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), and outcomes were defined as modified Rankin Scale and mortality status at 6 months post stroke.Of the 8052 patients with the LAA subtype of acute ischemic stroke in this study, 3312 (41.1%) had eGFR60 mL/min/1.73 m(2). The adjusted odds ratios of worse functional outcomes following a stroke were 1.10 (95% confidence interval [CI], 0.95-1.28), 1.60 (95% CI, 1.22-2.11) and 1.60 (95% CI, 1.10-2.33) in patients with eGFR 30-59, 15-29, and15 as compared with those with eGFR 60-119 mL/min/1.73 m(2), respectively. Increased risk of mortality was closely and independently related to high NIHSS scores and low eGFR levels. Stroke severity and eGFR were also synergistically related to 6-month mortality, with an adjusted hazard ratio of 21.19 (95% CI, 9.69-46.35) in patients with NIHSS15 and eGFR15 mL/min/1.73 m(2), compared with those with NIHSS 0-5 and eGFR 60-119 mL/min/1.73 m(2).Low eGFR was significantly and independently associated with 6-month functional outcomes and mortality in patients with the LAA subtype of acute ischemic stroke. The deleterious relationship between low eGFR levels and mortality following stroke was exacerbated by its synergistic association with stroke severity.