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Aim: Although a lower level of non-high-density lipoprotein cholesterol (HDL-C) was reported to be inversely associated with spontaneous intracranial hemorrhage (ICH), no enough evidence has verified whether lipid profiles modify hemorrhagic transformation and functional outcomes in patients with acute ischemic treated with thrombolysis. Methods: This multicenter cohort study included 2373 patients with acute ischemic stroke treated with intravenous thrombolysis between December 2004 and December 2016. Of these, 1845 patients were categorized into either the hyperlipidemia or non-hyperlipidemia group. Symptomatic ICH (SICH) rates within 24–36 h of thrombolytic onset and functional outcomes at 30 and 90 days were longitudinally surveyed. Models of predicting hemorrhagic transformation were used to validate our findings. Results: For enrolled 1845 patients, SICH rates were ≥ 2-fold reduced for the hyperlipidemia group by the NINDS (adjusted RR: 0.488 [0.281–0.846], p = 0.0106), the ECASS II (adjusted RR: 0.318 [0.130–0.776], p = 0.0119), and SITS-MOST standards (adjusted RR: 0.214 [0.048–0.957], p = 0.0437). The favorable functional rates between the two groups were not significantly different. Lower levels of LDL-C were showed in robust association with SICH. With a cut-off LDL-C value of < 130 mg/dL, new models are more robust and significant in predicting hemorrhagic transformation within 24–36 h. Conclusions: This study supports the strong association between reduced LDL-C and increased SICH, but not for functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. LDL-C level of < 130 mg/dL is supposed to a candidate marker for predicting SICH within 24–36 h.

OBJECTIVES Dabigatran etexilate is a direct thrombin inhibitor that clinicians increasingly prescribe to prevent stroke in patients with non-valvular atrial fibrillation (NVAF). Clinicians also commonly prescribe statins for primary and secondary prevention of cardiovascular diseases. Little is known about the bleeding risk in patients taking a statin and dabigatran together. The aim of this study was to evaluate the safety and persistence of dabigatran after co-medication with statins. MATERIALS AND METHODS We performed a prospective, multicenter registry study of stroke patients with NVAF who initiated dabigatran therapy within 3 months after a clinically evident ischemic cerebrovascular event between 2013 and 2017. The main outcome measure was symptomatic bleeding after 90, 180, and 360 days. RESULTS In total, 652 patients (336 statin users, 316 non-users) were followed for 1 year after dabigatran therapy. Cox multivariate analysis demonstrated that male sex, prior use of aspirin, and concurrent use of an antiarrhythmic drug were associated with a higher risk of bleeding at 360 days. After adjusting time-dependent covariates, statin users had a significantly lower bleeding risk (adjusted hazard ratio: 0.11, P

Supplemental Digital Content is available in the text., Background and Purpose: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. Methods: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Results: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001). Conclusions: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429.

Background: Cerebrovascular pathologies and hypertension could play a vital role in Alzheimer disease (AD) progression. However, whether cerebrovascular pathologies and hypertension accelerate the AD progression through an independent or interaction effect is unknown. Objective: To investigate the effect of the interactions of cerebrovascular pathologies and hypertension on AD progression. Method: A retrospective longitudinal study was conducted to compare AD courses in patients with different severities of cerebral White Matter Changes (WMCs) in relation to hypertension. Annual comprehensive psychometrics were performed. WMCs were rated using a rating scale for Age-related WMCs (ARWMC). Results: In total, 278 patients with sporadic AD were enrolled in this study. The mean age of the patients was 76.6 ± 7.4 years, and 166 patients had hypertension. Among AD patients with hypertension, those with deterioration in clinical dementia rating-sum of box (CDR-SB) and CDR had significantly severe baseline ARWMC scales in total (CDR-SB: 5.8 vs. 3.6, adjusted P = 0.04; CDR: 6.4 vs. 4.4, adjusted P = 0.04) and frontal area (CDR-SB: 2.4 vs. 1.2, adjusted P = 0.01; CDR: 2.4 vs. 1.7, adjusted P < 0.01) compared with those with no deterioration in psychometrics after adjustment for confounders. By contrast, among AD patients without hypertension, no significant differences in ARWMC scales were observed between patients with and without deterioration. Conclusion: The effect of cerebrovascular pathologies on AD progression between those with and without hypertension might differ. An interaction but not independent effect of hypertension and WMCs on the progression of AD is possible.

Cardiovascular fitness exerts directly beneficial effects on functional and cognitive outcomes in patients of chronic stroke. However, the effect of early rehabilitation on cardiovascular function has not yet been thoroughly examined. We tested whether complementary rehabilitation program could influence cardiovascular fitness in an early stage of stroke patients. The associations for post-acute stroke functional recovery with cardiovascular fitness were explored. Thirty-seven patients with mean poststroke interval of 8.6 ± 3.8 days underwent inpatient rehabilitation of 22.8 ± 3.8 days. Functional outcomes of 15.3 points (17.2%) in functional independence measure improved after rehabilitation program. The therapeutic cardiovascular fitness was determined in ramp exercise test on a cycling ergometer. Peak oxygen uptake (V˙O2peak) significantly increased by 24.8% after early stroke rehabilitation. Multivariate regression analysis was performed to assess for associations of functional improvement with respect to change in V˙O2peak and extremities motor impairment. V˙O2peak gain accounted for more functional recovery than extremities motor improvement (R2 = 0.42). In conclusion, these results suggest that cardiovascular fitness appears to increase after complementary program in early stroke rehabilitation, and better cardiovascular fitness may be associated with greater functional improvement. Keywords: Fitness, Oxygen uptake, Rehabilitation, 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.

Made available in DSpace on 2019-10-04T12:41:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-02 National Health and Medical Research Council of Australia Background-The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence-based processes of care for acute ischemic stroke (AIS) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Methods and Results-Use of 8 AIS processes of care were considered: reperfusion therapy in eligible patients; acute stroke unit care; antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation; dysphagia assessment; and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0-2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or defect-free care, was associated with improved outcome (odds ratio, 1.40; 95% CI, 1.18-1.65) and better survival (odds ratio, 2.23; 95% CI, 1.62-3.09). Defect-free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0-1) (odds ratio, 1.22; 95% CI, 1.04-1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and individual rates. Conclusions-Use of evidence-based care is associated with improved clinical outcome in AIS. Strategies are required to address regional variation in the use of proven AIS treatments. Univ New South Wales, Fac Med, George Inst Global Hlth, Sydney, NSW, Australia Ctr Estudios Clin, Inst Ciencias & Innovac Med, Santiago, Chile Clin Alemana Univ Desarrollo, Fac Med, Serv Neurol, Dept Neurol & Psiquiatria, Santiago, Chile Peking Univ, Hlth Sci Ctr, George Inst Global Hlth, Beijing, Peoples R China Australian Catholic Univ, Nursing Res Inst, St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Univ Cent Lancashire, Fac Hlth & Wellbeing, Preston, Lancs, England Univ Chile, Fac Med, Dept Ciencias Neurol, Santiago, Chile Univ Sao Paulo, Ribeirao Preto Med Sch, Stroke Serv Neurol Div, Ribeirao Preto, Brazil Fukuoka Univ, Fac Med, Dept Prevent Med & Publ Hlth, Fukuoka, Fukuoka, Japan Univ Leicester, Dept Cardiovasc Sci, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Leicester, Natl Inst Hlth Res, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland George Inst Global Hlth, Sydney, NSW, Australia Univ Desarrollo, Serv Neurol, Dept Neurol & Psiquiatria Clin Alemana Santiago, Santiago, Chile St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Australian Catholic Univ, Sydney, NSW, Australia Univ Cent Lancashire, Stroke Practice Res Unit, Sch Hlth, Lancashire Clin Trials Unit, Preston, Lancs, England Univ Leicester, Dept Cardiovasc Sci, Cardiovasc Res Ctr, British Heart Fdn, Leicester, Leics, England Univ Kelaniya, Dept Pharmacol, Fac Med, Colombo, Sri Lanka Christian Med Coll & Hosp, Dept Neurol, Ludhiana, India Kaohsiung Med Univ & Hosp, Dept Neurol, Kaohsiung, Taiwan Linkou Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan Peking Union Med Coll Hosp, Beijing, Peoples R China Univ Sao Paulo, Ribeirao Preto Sch Med, Ribeirao Preto, Brazil Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia Univ Cent Lancashire, Sch Hlth Sci, Coll Hlth & Wellbeing, Preston, Lancs, England Univ Desarrollo, Santiago, Chile Univ New South Wales, Neurosci Res Australia, Sydney, NSW, Australia Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore Bradford Royal Infirm, Bradford Inst Hlth Res, Leeds, W Yorkshire, England Christian Med College, Ludhiana, Punjab, India RemediumOne Pvt Ltd, Kandy, Sri Lanka Kaohsiung Med Univ, Chung Ho Mem Hosp, Kaohsiung, Taiwan Calvary Publ Hosp Bruce, Bruce, Australia Royal North Shore Hosp, St Leonards, NSW, Australia Royal Prince Alfred Hosp, Camperdown, NSW, Australia Concord Repatriat Gen Hosp, Camperdown, NSW, Australia Fiona Stanley Hosp, Camperdown, NSW, Australia Macquarie Base Hosp, Melbourne, Vic, Australia Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, Sao Paulo, Brazil Hosp Governador Celso Ramos, Florianopolis, SC, Brazil Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil Yangquan Coalmine Grp Gen Hosp, Yangquan, Peoples R China Nanjing Med Univ, Nanjing Hosp 1, Nanjing, Jiangsu, Peoples R China 85 Hosp Peoples Liberat Army, Beijing, Peoples R China Chifeng Univ, Affiliated Hosp, Chifeng, Peoples R China Beijing Pinggu Hosp, Beijing, Peoples R China Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Peoples R China Soochow Univ, Affiliated Hosp 2, Suzhou, Peoples R China Hebei Med Univ, Hosp 3, Shijiazhuang, Hebei, Peoples R China Capital Med Univ, Xuanwu Hosp, Beijing, Peoples R China Jining Med Univ, Affiliated Hosp, Jining, Peoples R China Third Peoples Hosp Huizhou, Huizhou, Peoples R China Second Cangzhou Cent Hosp, Cangzhou, Peoples R China Shanghai Jiao Tong Univ, Hosp Affiliated, Sch Med, Shanghai, Peoples R China Baogang Hosp, Baotou, Peoples R China Harbin Med Univ, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China Shanghai Jiao Tong Univ Sch, Tong Ren Hosp, Peoples Hosp Hejian City, Shanghai, Peoples R China Peking Univ, Shougang Hosp, Beijing, Peoples R China Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China Second Hosp Nanchang, Nanchang, Jiangxi, Peoples R China Bethune Int Peace Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China Shanghai Jiao Tong Univ, Sch Med, Shanghai Ninth Peoples Hosp, Shanghai, Peoples R China Shijiazhuang Cent Hosp, Shijiazhuang, Hebei, Peoples R China Hosp Base San Jos de Osorno, Osorno, Chile Christian Med Coll & Hosp, Ludhiana, Punjab, India Unit Narayana Hrudayalaya Ltd, Mazumdar Shaw Med Ctr, Bangalore, Karnataka, India Dr Ramesh Cardiac & Multispecial Hosp Pvt Ltd, Guntur, India Post Grad Inst Med Educ & Res, Chandigarh, India Baby Mem Hosp Ltd, Calicut, Kerala, India Sree Chitra Tirunal Inst Med Sci & Technol, Thiruvananthapuram, Kerala, India Sri Jayawardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka Colombo North Teaching Hosp, Colombo, Sri Lanka Colombo South Coching Hosp, Colombo, Sri Lanka Linkou Chang Gung Mem Hosp, Taoyuan, Taiwan Taipei Med Univ, Shuang Ho Hosp, Taipei, Taiwan En Chu Kong Hosp, New Taipei, Taiwan Natl Cheng Kung Univ Hosp, Tainan, Taiwan Queen Alexandra Hosp, Portsmouth, Hants, England Portsmouth Hosp NHS Natl Hlth Serv iTrust, Portsmouth, Hants, England Univ Coll London Hosp NHS Fdn Trust, London, England Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England Southend Univ Hosp NHS Fdn Trust, Southend On Sea, England Kings Coll Hosp London, London, England York Teaching Hosp NHS Fdn Trust, York, N Yorkshire, England Nottingham Univ Hosp NHS Trust, Nottingham, England Blackpool Teaching Hosp NHS Fdn Trust, Blackpool, England Gloucestershire Hosp NHS Fdn Trust, Gloucestershire Royal Hosp, Gloucester, England Teaching Hospi NHS Fdn Trust, London, England Royal Cornwall Hosp NHS Trust, Truro, England Royal London Hosp, Barts Hlth NHS Trust, London, England Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge, England Royal Victoria Hosp, Belfast Hlth & Social Care Trust, London, England Pinderfields Gen Hosp, Mid Yorkshire Hosp NHS Trust, Wakefield, England Royal Devon & Exeter NHS Fdn Trust, London, England Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England Great Western Hosp NHS Fdn Trust, Swindon, Wilts, England Watford Dist Gen Hosp, Watford, England Imperial Coll Healthcare NHS Trust, London, England Medway NHS Fdn Trust, Gillingham, England Royal Liverpool & Broadgreen Univ NHS Trust, Liverpool, Merseyside, England Calderdale & Huddersfield NHS Fdn Trust, Huddersfield, W Yorkshire, England Hywel Dda Univ Hlth Board, Haverfordwest, Wales Chesterfield Royal Hosp NHS Fdn Trust, Calow, England Luton & Dunstable Univ Hosp NHS Fdn Trust, Luton, Beds, England Countess Chester Hosp NHS Fdn Trust, Chester, Cheshire, England Peterborough City Hosp, Peterborough, Cambs, England Univ Hosp Leicester NHS Trust, Leicester Royal Infirm, Leicester, Leics, England Dist Hosp NHS Fdn Trust, London, England Barnsley Hosp NHS Fdn Trust, Barnsley, England Dorset Cty Hosp NHS Fdn Trust, Dorchester, England Royal Bournemouth & Christchurch Hosp NHS Fdn Tru, Royal Bournemouth Hosp, Bournemouth, Dorset, England Southern Hlth & Social Care Trust, Craigavon Area Hosp, Portadown, England United Lincolnshire Hosp NHS Trust, Pilgrim Hosp, Lincoln, England Bedford Hosp NHS Trust, Bedford, England Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil National Health and Medical Research Council of Australia: 1066966

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis and conveys a significant health burden globally. Critical limb ischaemia encompasses the most severe consequence of PAD. Our previous studies indicate that microRNA let‐7g prevents atherosclerosis and improves endothelial functions. This study aimed to investigate whether and how let‐7g therapy may improve blood flow to ischaemic limbs. The present study shows that let‐7g has multiple pro‐angiogenic effects on mouse ischaemic limb model and could be a potential therapeutic agent for PAD. Mice receiving intramuscular injection of let‐7g had more neovascularization, better local perfusion and increased recruitment of endothelial progenitor cells after hindlimb ischaemia. The therapeutic effects of let‐7g's on angiogenesis are mediated by multiple regulatory machinery. First, let‐7g increased expression of vascular endothelial growth factor‐A (VEGF‐A) and VEGF receptor‐2 (VEGFR‐2) through targeting their upstream regulators HIF‐3α and TP53. In addition, let‐7g affected the splicing factor SC35 which subsequently enhanced the alternative splicing of VEGF‐A from the anti‐angiogenic isoform VEGF‐A165b towards the pro‐angiogenic isoform VEGF‐A164a. The pleiotropic effects of let‐7g on angiogenesis imply that let‐7g may possess a therapeutic potential in ischaemic diseases.

Case-control studies have shown that noxious thermal stimulation (TS) can improve arm function in patients with stroke. However, the neural mechanisms underlying this improvement are largely unknown. We explored functional neural activation due to noxious and innocuous TS intervention applied to the paretic arm of patients with stroke. Sixteen participants with unilateral cortical infarctions were allocated to one of two groups: noxious TS (8 patients; temperature combination: hot pain 46°C to 47°C, cold pain 7°C–8°C) or innocuous TS (n = 8; temperature combination: hot 40°C–41°C, cold 20°C–21°C). All subjects underwent fMRI scanning before and after 30 min TS intervention and performed a finger tapping task with the affected hand. Immediate brain activation effects were assessed according to thermal type (noxious vs. innocuous TS) and time (pre-TS vs post-TS). Regions activated by noxious TS relative to innocuous TS (P

Background and purpose The optimal dose of alteplase for acute ischemic stroke among geriatric patients is unclear. We aimed to assess the efficacy and safety of a low-dose (0.6 mg/kg) and standard-dose (0.9 mg/kg) alteplase for varying severity of Asian geriatric stroke patients. Methods The favorable functional outcome on day 90 after stroke onset, and the symptomatic intracranial hemorrhage (SICH) rate following 24–36 h of intravenous alteplase were measured. The baseline NIHSS of 4–8, 9–13, ≥14 were defined as mild, moderate, and high severity, respectively. Results Totally, 249 geriatric patients treated with low-dose (n = 108) and standard-dose (n = 141) alteplase. Compared to standard-dose alteplase, low-dose alteplase had decrease in favorable functional outcome (22.2% versus 34.8%), and no difference in SICH rates was observed. For mild severity patients, the mortality was significantly increased with standard-dose alteplase (the NNT/NNH = 22.9/8.0 for mild severity, the NNT/ NNH = 15.0/14.7 for moderate severity, and the NNT/NNH = 13.5/19.6 for high severity). Conclusions Standard-dose and low-dose alteplase were comparable in reducing major disability, but low-dose alteplase for mild stroke showed much reduced mortality on day 90 for octogenarians.

Poorly controlled blood glucose was reported to cause deterioration of acute ischemic stroke. In this study, we investigated whether an elevated admission serum glucose level in the 3-h time window of intravenous thrombolysis for acute ischemic stroke determined poor functional outcomes among Chinese population.This was a prospective cohort study. From December 1, 2004 to December 31, 2016, a total of 2370 patients were enrolled and categorized into two cohorts by blood glucose levels of ≥200 and200 mg/dl in the 3 h after stroke onset. The primary objective was to determine whether admission hyperglycemia increased major disability and death at 30 and 90 days, which was defined by a modified Rankin Scale of 3-6. The secondary objective was to determine whether admission hyperglycemia increased the symptomatic intracranial hemorrhage (SICH) at 90 days. The number needed to harm (NNH) and patient expected event rate (PEER) were evaluated for both the primary and secondary objectives.The primary outcome occurred in 216 of 305 patients (70.8%) in the blood glucose ≥200 mg/dl cohort and in 951 of 1587 patients (59.9%) in the blood glucose200 mg/dl cohort at 30 days, and in 191 of 287 patients (66.6%) in the blood glucose ≥200 mg/dl cohort and in 827 of 1517 patients (54.5%) in the blood glucose200 mg/dl cohort at 90 days. Patients with admission hyperglycemia had significantly increased major disability and death at 30 (adjusted relative risk (RR): 1.194 [1.073-1.329], p = 0.0012) and 90 days (adjusted RR: 1.203 [1.079-1.340], p = 0.0008). Admission hyperglycemia increased the risk of the occurrence of SICH by nearly 2-fold (adjusted RR: 1.891 [0.977-3.657], p = 0.0585 with the SITS-MOST criteria and adjusted RR: 1.884 [1.138-3.121], p = 0.0139 with the NINDS criteria). NNH values of admission hyperglycemia in major disability and death at 30 and 90 days were 9 and 10, and NNH values of SICH by the SITS-MOST NINDS criteria were 44 and 34, respectively.The study evidenced the association and temporal relationship of admission hyperglycemia causing deterioration of functional outcomes and increased SICH among Chinese population with acute ischemic stroke treated with intravenous thrombolysis.

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.

The early identification of patients with large hemisphere infarctions (LHIs) at risk of fatal brain edema may result in better outcomes. A quantitative model using parameters obtained at admission may be a predictor of in-hospital mortality from LHI. This prospective study enrolled all patients with LHI involving >50% of the middle cerebral artery (MCA) admitted to our neurological intensive care unit within 48 hours of symptom onset. Early clinical and radiographic parameters and the baseline CHADS2 score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke [double weight]) were analyzed regarding their ability to predict patient outcomes. Seventy-seven patients with LHIs were identified, 33 (42.9%) with complete MCA infarction (CMCA), and 44 (57.1%) with incomplete MCA infarction (IMCA). The predictors of CMCA score included: >1/3 early hypodensity in computed tomography findings, hyperdense MCA sign, brain edema, initial National Institutes of Health Stroke Scale (NIHSS) score ≥17, and stroke in progression during the 1st 5 days of admission. The cutoff CMCA score was 2, with a sensitivity of 81.8% and specificity of 70.5%. Mortality score 1, used for predicting in-hospital mortality from LHI, included CMCA and CHADS2 scores ≥4 (sensitivity 100.0%, specificity 57.4%), and mortality score 2 included CMCA and CHADS2 scores ≥4, and NIHSS score ≥26, during the 1st 5 days (sensitivity 100.0%, specificity 91.7%). Patients qualifying for a mortality score of 2 were at high-risk of in-hospital mortality from LHI. These findings may aid in identifying patients who may benefit from invasive therapeutic strategies, and in better describing the characteristics of those at risk of mortality.

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 (

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.

Vertigo can be a major presentation of posterior circulation stroke and can be easily misdiagnosed because of its complicated presentation. We thus prospectively assessed the predictive value of vertebral artery extracranial color-coded duplex sonography (ECCS) for the prediction of ischemic stroke-related vertigo. The inclusion criteria were: (1) a sensation of whirling (vertigo); (2) intractable vertigo for more than 1 hour despite appropriate treatment; and (3) those who could complete cranial magnetic resonance imaging (MRI) and vertebral artery (V2 segment) ECCS studies. Eventually, 76 consecutive participants with vertigo were enrolled from Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan between August 2010 and August 2011. Demographic data, neurological symptoms, neurologic examinations, and V2 ECCS were assessed. We chose the parameters of peak systolic velocity (PSV), end diastolic velocity (EDV), PSV/EDV, mean velocity (MV), resistance index (RI), and pulsatility index (PI) to represent the hemodynamics. Values from both sides of V2 segments were averaged. We then calculated the average RI (aRI), average PI (aPI), average PSV (aPSV)/EDV, and average (aMV). Axial and coronal diffusion-weighted MRI findings determined the existence of acute ischemic stroke. We grouped and analyzed participants in two ways (way I and way II analyses) based on the diffusion-weighted MRI findings (to determine whether there was acute stroke) and neurological examinations. Using way I analysis, the “MRI (+)” group had significantly higher impedance (aRI, aPI, and aPSV/EDV ratio) and lower velocity (aPSV, aEDV, and aMV(PSV + EDV/2)), compared to the “MRI (–)” group. The cutoff value/sensitivity/specificity of aPSV, aEDV, aMV, aPI, aRI, and aPSV/EDV between the MRI (+) and MRI (–) groups were 41.15/61.5/66.0 (p = 0.0101), 14.55/69.2/72.0 (p = 0.0003), 29.10/92.1/38.0 (p = 0.0013), 1.07/76.9/64.0 (p = 0.0066), 0.62/76.9/64.0 (p = 0.0076), and 2.69/80.8/66.0 (p = 0.0068), respectively. Using way II analysis, lower aEDV and aMV, and higher aRI, aPI, and aPSV/EDV ratio could determine the “MRI (+) without focal signs” group. The cutoff value/sensitivity/specificity of aEDV, aMV, aPI, aRI, and aPSV/EDV between the MRI (+) without focal signs and MRI (–) groups were 9.10/71.4/96.0 (p = 0.0005), 15.65/57.1/96.0 (p = 0.0124), 1.10/100/70.0 (p = 0.0002), 0.64/100/70.0 (p = 0.0023), and 2.80/100/70.0 (p = 0.0017), respectively. In conclusion, using demographic data and clinical symptoms, it was difficult to determine the patients with ischemic stroke-related vertigo. Although neurological examinations still have diagnostic value, the high impedance and low velocity pattern of V2 ECCS can be an add-on method for the screening of acute ischemic stroke-related vertigo, even for those without focal neurological signs.

Objective Single nucleotide polymorphisms (SNPs) located at microRNA (miRNA) binding sites (miR-SNPs) can affect the expression of genes. This study aimed to identify the miR-SNPs associated with atherosclerosis and stroke. Methods Patients with ischemic stroke ( n = 657) and stroke- and myocardial infarction-free volunteers ( n = 1571) were enrolled. The carotid intima-media thickness (IMT) was measured in the control participants. Seventy-nine stroke susceptibility genes were initially selected and 13 genes were predicted to have miR-SNPs at their 3′ untranslated regions (3′UTR). The miRNA arrays were used to further identify potential miR-SNPs. The miR-SNP rs3735590 at the paraoxonase 1 (PON1) gene was finally selected and its associations with stroke and carotid IMT were evaluated. The 3′UTR reporter and SNP functional assays were then performed to validate the results. Results Compared with CC genotype, patients with CT or TT genotype at rs3735590 had lower risk of ischemic stroke (OR = 0.72, p = 0.036; OR = 0.83, p = 0.077, respectively). Among the healthy participants, the CT or TT genotype was associated with thinner IMT in the internal carotid arteries in comparison with CC genotype ( β = −0.76, p = 0.003; β = −0.022, p = 0.452, respectively). Our findings suggested that the minor allele T had a protective effect on atherosclerosis. Results from 3′UTR reporter assays showed that PON1 is a direct target gene of miR-616. In plasmid constructs carrying the risk allele C at rs3735590, miR-616 inhibited the genetic expression of PON1. However, substitution of C by T at rs3735590 reduced the miR-616 binding affinity, leading to overexpression of the PON1 gene. Conclusion Our study is the first to show that the miR-SNP at PON1 could affect genetic expression and is associated with an elevated risk for ischemic stroke and subclinical atherosclerosis.

Autonomic cardiac dysfunction is a common complication after acute ischemic stroke (IS). We recruited 75 patients with acute IS with measurements of autonomic cardiac function, including heart rate variability (HRV) and associated parameters, and compared them with 81 controls. Of the 75 patients, 28 had right hemispheric infarctions (RH), 29 had left hemispheric infarctions (LH), and 18 had brainstem infarctions (BS). A comparison of HRV in all patients with stroke and in control subjects showed significant differences between IS subgroups and controls in low frequency (LF), high frequency (HF), normalized LF, normalized HF, and LF/HF ranges. A post-hoc comparison identified significant differences between patients with IS with BS infarctions and the control group in LF, HF, and LF/HF ranges. BS infarction may cause a much greater increase in sympathetic modulation and reduced vagal activity compared to RH or LH infarction. Our findings provide evidence that acute IS causes significant damage to the cardiovascular autonomic system, manifesting as abnormalities of HRV. BS stroke might correlate with a significant reduction in parasympathetic and an increase in sympathetic influence on HRV.

Circadian variation of the onset time of acute ischemic stroke has been well studied. However, little is mentioned about the circadian variation of discharge-stroke severity and discharge-functional status. This study evaluated the impact of onset time on discharge-stroke severity and the functional status of acute ischemic stroke. Brain magnetic resonance imaging was performed on 274 acute ischemic stroke patients (66.42% male; mean age = 64.81 ± 12.80 years). All times of onset were assigned to 4-hourly periods (six groups) starting from midnight. Stroke severity/functional status was evaluated on admission and discharge using the National Institute of Health Stroke Scale (NIHSS) score/modified Rankin Scale (mRS) and Barthel Index (BI), respectively. Using mRS, but not NIHSS score and BI, it was possible to differentiate the best and worst groups on discharge. Patients in group 2 (4 to

Background/Aims: MicroRNA miR-21, miR-221 and miR-145 have been implicated in the cardiovascular system. We aimed to compare the serum levels of the three microRNAs (miRNAs) in different severities of cerebrovascular diseases and evaluate the feasibility of using these miRNAs as biomarkers for stroke. Methods: We enrolled 167 subjects with ischemic stroke, 66 atherosclerosis subjects with any carotid plaque score and 157 healthy controls. These three types of subjects represent three levels of severity in cerebrovascular diseases. Analysis of covariance was used to evaluate the relationship between miRNAs and disease severity with adjustment for conventional risk factors. To test the prediction for stroke, we built regression models containing the serum miRNA levels and risk factors. Prediction capabilities were compared by the receiver operating characteristic curves. Results: Stroke patients and atherosclerosis subjects had significantly higher miR-21 and lower miR-221 serum levels than healthy controls, while the miR-145 expression was too low to provide useful information in this regard. The best model showed that miR-21 and miR-221 were independent predictors. There was a 6.2-fold increase for stroke risk when miR-21 levels increase by log102-ΔCt = 1, while a 10.4-fold increase was observed as miR-221 decreases by log102-ΔCt = 1. Conclusions: Serum miR-145 was not detected in over 50% of the patients and it may not be an ideal marker to predict stroke. MiR-21 and miR-221 are novel biomarkers for atherosclerosis and stroke.

Background Thermal stimulation (TS) has been developed and incorporated into stroke rehabilitation. However, whether noxious and innocuous TS induce the same effects on motor function recovery after stroke is still unknown. A comparative study of different temperature combination regimens is needed. Objective To compare the short- and long-term effectiveness between noxious and innocuous TS on motor recovery of upper extremity in patients with acute stroke. Design Randomized, controlled trial with concealed allocation, intention-to-treat analysis and blinded outcome assessors. Setting A university hospital rehabilitation department in Taiwan. Participants A total of 79 patients with acute ischemic stroke were recruited. The majority had moderate to severe motor impairment of the upper extremity (UE). Intervention In addition to traditional rehabilitation, the experimental group (n = 39) underwent noxious TS (heat pain 46-47°C/cold pain 7-8°C), and the control group (n = 40) received innocuous TS (heat 40-41°C/cold 20-21°C). TS intervention was applied for 30 minutes once per day and for a total of 20-24 times during hospital stay. A custom-made TS instrument, comprising 2 thermal stimulators and their respective thermal pads constructed in a closed-loop system, was used. Outcomes The Fugl-Meyer upper extremity score (the primary outcome), Action Research Arm Test, Motricity Index, Barthel Index, and modified Ashworth scale (the secondary outcomes) were administered by a blinded assessor at baseline, post–12th TS, post-intervention, 1-month, and 6-month follow-ups. Results No significant differences between groups were found on the primary outcome at postintervention and follow-up assessments. At 1-month follow-up, the innocuous group showed a small effect (partial η 2 = 0.02) that was greater than that of the noxious group, but that effect was eliminated at 6 months. Both groups presented significant within-group improvements over time (both P Conclusions Combining noxious TS with traditional rehabilitation did not yield better short-term or long-term results than combining innocuous TS with traditional rehabilitation on UE functional recovery for individuals with acute stroke. Level of Evidence II

AIM: Atherosclerotic diseases are the leading cause of death worldwide. Longitudinal changes in carotid intima-media thickness (IMT) and plaque are being increasingly used as markers of atherosclerosis progression and may predict future cardiovascular events. This study aimed to investigate the predictors of carotid IMT and plaque progression in a Chinese population and to determine whether these predictors differ by gender. METHODS: Segment-specific carotid IMT and plaque were measured in 712 stroke- and myocardial infarction-free subjects at baseline and after an average interval of 4.3 ± 0.9 years. Multivariate linear regression and logistic regression analyses were conducted to investigate the predictive effect of age, gender, and cardiovascular risk factors on carotid IMT and plaque progression. Gender-specific analyses were also performed. RESULTS: Overall, age and smoking were predictors of common carotid artery IMT progression (adjusted p < 0.001 and p = 0.045, respectively). Age, hypertension, and use of antihypertensive medication were predictors of bifurcation IMT progression (adjusted p < 0.001, p = 0.033, and p

Background and Purpose Large artery stiffness is considered to be a marker for cardiovascular disease. Serum matrix metalloproteinase-9 (MMP-9) level has been found to correlate with arterial stiffness and predict cardiovascular risk. This study was aimed to investigate the relationship between the MMP-9 genotypes and artery stiffness, and to examine whether the genetic effect is sex specific. Methods Three carotid stiffness modalities were assessed in 1218 (704 females) stroke- and myocardial infarction-free volunteers aged 21–86 years old. The genotypes of MMP-9 promoter polymorphism (-1562C/T) were determined using the polymerase chain reaction-restriction fragment length polymorphism method. Analysis was conducted to test for the overall and sex specific effect using multivariate regression model. Results T allele carriers (CT and TT) had stiffer arteries than CC homozygotes after adjusting for age and sex ( p = 0.013, 0.028, and 0.017 for Ep, β , and PWV, respectively). Further sex-stratified analysis showed that the significant association only existed in women. Women with the T allele had significantly stiffer arteries than CC homozygotes after adjusting for age ( p = 0.003, 0.018, and 0.006 for Ep, β , and PWV, respectively), and this association remained significant after adjusting for known covariates. When menopausal status was further considered, all three carotid stiffness modalities were significantly different between T allele carriers and CC homozygotes in menopausal but not in pre-menopausal women. Conclusions This study indicates that individuals carrying the -1562T allele are predisposed to stiffer arteries, especially among menopausal women. Women with the T allele should be considered at high risk for cardiovascular disease.

Aims Proliferation and migration of vascular smooth muscle cells (VSMCs) can cause atherosclerosis and neointimal formation. MicroRNAs have been shown to regulate cell proliferation and phenotype transformation. We discovered abundant expression of microRNA-195 in VSMCs and conducted a series of studies to identify its function in the cardiovascular system. Methods and results MicroRNA-195 expression was initially found to be altered when VSMCs were treated with oxidized low-density lipoprotein (oxLDL) in a non-replicated microRNA array experiment. Using cellular studies, we found that microRNA-195 reduced VSMC proliferation, migration, and synthesis of IL-1β, IL-6, and IL-8. Using bioinformatics prediction and experimental studies, we showed that microRNA-195 could repress the expression of Cdc42, CCND1, and FGF1 genes. Using a rat model, we found that the microRNA-195 gene, introduced by adenovirus, substantially reduced neointimal formation in a balloon-injured carotid artery. In situ hybridization confirmed the presence of microRNA-195 in the treated arteries but not in control arteries. Immunohistochemistry experiments showed abundant Cdc42 in the neointima of treated arteries. Conclusions We showed that microRNA-195 plays a role in the cardiovascular system by inhibiting VSMC proliferation, migration, and proinflammatory biomarkers. MicroRNA-195 may have the potential to reduce neointimal formation in patients receiving stenting or angioplasty.

Introduction Early diagnosis and treatment of central nervous system (CNS) tuberculosis (TB) are very important because of its high morbidity and mortality characteristics. However, the clinical symptoms, laboratory and neuroimaging findings of CNS TB are nonspecific, no matter whether they are the common form, tuberculous meningitis (TBM), or the rare form, intracranial tuberculomas. We report a case of TBM with miliary pattern of intracranial tuberculomas, although the initial diagnosis was masked by an atypical neuropsychiatric presentation, cerebrospinal fluid (CSF) finding, and other medical comorbidity. Case report A 51-year-old man was brought to the emergency room due to a traffic accident. The initial impression was Wernicke encephalopathy due to his alcohol use history and the clinical triad. After admission, fever and mental confusion lead to the suspicion of CNS infection. Although the initial CSF analysis was inconclusive, the miliary pattern of intracranial tuberculomas was highly suspected by brain magnetic resonance imaging finding. The diagnosis of TBM and miliary TB was finally confirmed by positive CSF and sputum culture of Mycobacterium tuberculosis. The patient had a good response to standard antituberculous therapy, although paradoxical expansion of cerebral tuberculomas occurred during treatment. Conclusions TB is still a major public health problem in the world, and there is a rising tendency of extrapulmonary TB incidences in the developed countries. Because of the high mortality and treatable characteristics of CNS TB, physicians should be familiar with it and keep the diagnosis in mind.

Introduction Connexin 37, encoded by the GJA4 gene, protects against atherosclerosis. A recent study reported an association between polymorphism rs1764391 at GJA4 and ischemic stroke in a Chinese population. We aimed to replicate this result. Materials and Methods A total of 958 ischemic stroke patients and 2196 controls were enrolled for the study. All participants were Chinese residing in Taiwan. Logistic regression analysis with adjustment for traditional risk factors was used to estimate the genetic effect. We also performed stratification analyses by sex and stroke subtypes. Literature reviews were conducted for available genetic association studies investigating rs1764391 and cardiovascular phenotypes. Results We did not find any significant association for overall stroke (p = 0.87) or from any subset analyses. Eight studies addressing the associations between rs1764391 and cardiovascular phenotypes had a sample size greater than 1000. Including the present study, five out of the eight large-scale studies found no association. Conclusions GJA4 polymorphism is not associated with stroke risk in the Taiwanese population.

Decompressive craniectomy reduces fatality in patients with space-occupying infarctions. However, mortality remains high. We aimed to identify predictors of in-hospital mortality and outcomes in a cohort of patients with large hemispheric stroke receiving decompressive craniectomy.We retrospectively reviewed all patients diagnosed with complete middle cerebral artery infarction and receiving decompressive craniectomy. Hospital characteristics were compared among different groups (survivors versus non-survivors, good outcome versus poor outcome). A total of 71 consecutive patients were enrolled.From 2004 January to 2010 April, 71 patients were enrolled whose mean age was 65.11 ± 13.13 years and 33 (46.5%) of these were men. The in-hospital mortality was 28.2% overall. Of the patients who survived and were discharged, 37 (77.1%) had poor outcome (mRS 4-6) and 11 (22.9%) had good outcome (mRS 0-3). Pre-operation brain computed tomography (CT) hypodensity volume (p = 0.001) was significantly associated with mortality. In binary logistic regression model, pre-operation brain CT hypodensity volume (OR = 1.015; 95% CI, 1.001 to 1.030) and age (OR = 1.112; 95% CI, 1.017 to 1.215) were both significantly associated with outcomes.In patients with large hemispheric stroke receiving decompressive craniectomy, pre-operation brain CT hypodensity volume was significantly associated with in-hospital mortality whereas age was not. Pre-operation brain CT hypodensity volume and age were predictors of outcomes in those who survived the acute phase.

Cardiac autonomic dysfunction is a common complication after acute ischemic stroke (IS). Prior investigators have emphasized that infarction of brain stem or hemispheres with insular involvement is related to this dysfunction and may predict poor clinical outcome. From the viewpoint of stroke physicians, however, all stroke patients, particularly large-artery atherosclerosis (LAA) should be monitored for possible cardiac complications after acute IS. This study aimed to investigate cardiac autonomic impaction in patients with acute IS and to make the comparison between LAA and small-vessel occlusion (SVO) subtypes. Of the 126 acute IS patients prospectively enrolled in this study, 32 had LAA, 56 had SVO, and 38 had undetermined etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Cardiac autonomic function of all patients was assessed by measuring heart rate variability (HRV). The low- and high-frequency components of HRV in all stroke patients were significantly lower than those of control subjects after comparing multivariable models, including additional adjustments for age, gender, and all risk factors. There were no significant differences on HRV between LAA and SVO although post hoc comparisons showed that stroke patients of SVO had increased sympathetic modulation and reduced vagal activity. In conclusion, in acute IS patients, both LAA and SVO are predisposed to have cardiac autonomic dysfunction, manifesting as abnormalities in HRV, whether in hemispheric or brain stem lesions. Stroke patients of SVO are at higher risks of cardiac abnormalities, which might suggest an early cardiac dysfunction because of long-term hypertension. The HF component of HRV thought to be for vagal control might be a cardinal marker for predicting cardiac autonomic dysfunction after acute IS. Short-term HRV spectral analysis is a convenient approach for stroke clinicians to assess autonomic function in acute stroke. Long-term follow-up for HRV and clinical outcome relative to LAA and SVO stroke subtypes is warranted, particularly when an abnormal HRV is found at admission.

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.

Objective We assessed the correlation between intima-media thickness (IMT) and stiffness and test whether they are independent risk factors for atherosclerotic diseases. Methods We enrolled 2333 participants from the general population. Among the study subjects, 197 subjects had a history of stroke or myocardial infarction (MI) and were treated as patients, and the rest were the control subjects. Intima-media thickness was measured at the common carotid artery (CCA), bifurcation, and internal carotid artery. Three parameters (arterial stiffness [β], elastic modulus, and pulse wave velocity) were measured for carotid stiffness. Correlation between IMT and stiffness was first calculated. Multivariate regression model was used to evaluate whether inclusion of both IMT and stiffness can increase the prediction of cardiovascular events. Results Only CCA and bifurcation IMTs were significantly and positively correlated with stiffness. After adjusting for age and sex, the correlations were substantially attenuated. Common carotid artery IMT was most significantly associated with stroke and MI ( P = 2.6 × 10−8) followed by bifurcation IMT ( P = 5.5 × 10−6), and internal carotid artery IMT was least significant ( P = 0.02). For stiffness, β was most significant ( P = 3.6 × 10−8) for stroke and MI, followed by elastic modulus ( P = 1.1 × 10−6) and pulse wave velocity ( P = 6.8 × 10−6). The best model for the combined effect was from β ( P < 0.03) and CCA ( P = 0.056) or bifurcation IMT ( P = 0.057). Conclusions Carotid IMT and stiffness represent different properties of atherosclerotic vessel wall. Measuring both traits provides a better characterization of atherosclerosis.

Background and purpose The metabolic syndrome (MS) is associated with a high risk for cardiovascular disease. Intima-media thickness (IMT) and stiffness reflect structure and functional alterations in arteries. We investigated the relationship of MS on IMT and stiffness and also dissected its gender and age specific effect. Methods Carotid segment-specific IMT and stiffness were obtained in 1245 stroke- and myocardial infarction free volunteers between the ages of 15 and 87. The MS was defined according to the National Cholesterol Education Program Adult Treatment Panel III with Asian modification. Results The prevalence of MS was 22.2% in our study population. The MS was associated with increased IMT in the common carotid artery (CCA IMT) and stiffness modalities (including Ep, β , and PWV), but was not associated with bifurcation and internal carotid artery IMT. The relationship of MS on atherosclerosis was more prominent in women than in men. Only women revealed a significant interaction between MS and age for CCA IMT ( p =0.013), which was more pronounced in young women (≤45 years) than in elderly. Comparing the risk components between young and elderly women in regard to MS, high triglycerides were more common in the affected young women ( p =0.007). Conclusions MS is associated with a risk for increased CCA IMT and stiffness, and this relationship is particularly pronounced in women. Age can modify the MS impact on atherosclerosis. Young women with MS who often have high triglycerides experience the highest risk to associate with atherosclerosis. Young MS women who are easily overlooked for atherosclerotic diseases need more detailed assessment for atherosclerosis to prevent premature cardiovascular disease.

Objectives Early diagnosis and monitoring of disease progression have become vital in clinical practice as disease modifying treatments for Alzheimer’s disease (AD) become available. This one-year prospective study aimed to clarify the usefulness of event-related potentials (ERPs) in cognitive decline and elucidate their cognitive significance in AD. Methods Using the Cognitive Abilities Screening Instrument (CASI) and ERPs, probable AD patients, mild cognitive impairment (MCI) patients, and normal controls were recruited. Results The AD and MCI patients had significantly decreased cognitive function and manifested a delay of P300 latency. The P300 latencies demonstrated significantly more prolongation than their baseline values in probable AD and MCI patients, although their CASI scores showed no statistically significant decline. Whereas N100, P200, and N200 components did not reach statistical differences between groups either in the baseline or follow-up assessments and did not show significant change on follow-up. Conclusion The combination of neuropsychological tests and P300 measurements proved useful in improving reliability and increasing sensitivity to early cognitive decline or disease progression in AD patients. Significance The P300 latency may reflect cognitive decline more sensitively than neuropsychological tests in the longitudinal follow-up of AD patients.

Background: Growing evidence suggests that white matter hyperintensities (WMHs) are implicated in stroke recurrence and mortality, and their location can be a critical factor. This study evaluated the impact of periventricular WMHs (PVWMHs) and subcortical WMHs (SWMHs) on poststroke functional outcomes. Methods: Brain MRI was performed on 187 acute ischemic stroke patients (57.8% male; mean age = 64.3 years) recruited from the Kaohsiung Municipal Hsiao-Kang Hospital from February 2007 to January 2008. A Fazekas score ≥2 in the periventrcular or subcortical white matter was taken as presence of WMHs. Demographic data and risk factors for stroke were assessed. Functional stroke outcomes were evaluated 30 days after stroke using the Barthel Index (BI) and the modifiedRankin Scale (mRS). Results: WMHs were inversely linked to favorable functional outcome measured by mRS (p = 0.001) and BI (p = 0.003). Evaluating different locations, PVWMHs were associated with unfavorable functional outcomes (p = 0.002, mRS; p = 0.001, BI). SWMHs were related to mRS (p = 0.026) but not BI (p = 0.069). After controlling other stroke risk factors, infarct volumes and initial stroke severity, PVWMHs were a significant indicator for both mRS (OR = 2.76; 95% CI = 1.03–7.40) and BI (OR = 3.07; 95% CI = 1.13–8.40), but SWMHs were not. Conclusions: Unfavorable functional stroke outcome is associated with MRI WMHs. In terms of location, PVWMHs but not SWMHs are related to functional stroke outcome.

BackgroundFunctional limitation of the upper extremities is common in patients with stroke. An upper-extremity measure with sound psychometric properties is indispensable for clinical and research use.ObjectiveThe purpose of this study was to compare the psychometric properties of 4 clinical measures for assessing upper-extremity motor function in people with stroke: the upper-extremity subscale of the Fugl-Meyer Motor Test (UE-FM), the upper-extremity subscale of the Stroke Rehabilitation Assessment of Movement, the Action Research Arm Test (ARAT), and the Wolf Motor Function Test.DesignThis was a prospective, longitudinal study.MethodsFifty-three people with stroke were evaluated with the 4 measures at 4 time points (14, 30, 90, and 180 days after stroke). Thirty-five participants completed all of the assessments. The ceiling and floor effects, validity (concurrent validity and predictive validity), and responsiveness of each measure were examined. Interrater reliability and test-retest reliability also were examined.ResultsAll measures, except for the UE-FM, had significant floor effects or ceiling effects at one or more time points. The Spearman ρ correlation coefficient for each pair of the 4 measures was ≥.81, indicating high concurrent validity. The predictive validity of the 4 measures was satisfactory (Spearman ρ, ≥.51). The responsiveness of the 4 measures at 14 to 180 days after stroke was moderate (.52 ≤ effect size ≤ .79). The 4 measures had good interrater reliability (intraclass correlation coefficient [ICC], ≥.92) and test-retest reliability (ICC, ≥.97). Only the minimal detectable changes of the UE-FM (8% of the highest possible score) and the ARAT (6%) were satisfactory.LimitationsThe sample size was too small to conduct data analysis according to type or severity of stroke. In addition, the timed component of the Wolf Motor Function Test was not used in this study.ConclusionsAll 4 measures showed sufficient validity, responsiveness, and reliability in participants with stroke. The UE-FM for assessing impairment and the ARAT for assessing disability had satisfactory minimal detectable changes, supporting their utility in clinical settings.

In the era of thrombolytic therapy for hyperacute ischemic stroke, most investigators have focused their attention on the factors influencing mortality and functional outcomes in patients treated with thrombolysis, but very few have focused on these factors among patients not receiving thrombolysis. The aim of this study was to investigate the prognostic factors for mortality in all hyperacute stroke patients with or without thrombolysis. In 2005, we enrolled 101 ischemic stroke patients (43 females, 58 males; mean age, 68 years) who were transported to the emergency department (ED) within 4 hours of symptom onset. The overall in-hospital mortality rate was 17.8% (18/101). According to t test analysis, age (p = 0.034), time interval from neurologist consultation (p < 0.0001) and ED to ward admission (p = 0.001), Glasgow coma scale (GCS) (p = 0.001), National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001) and the sum of major risk factors of cerebrovascular disease (CVD) (p < 0.0001) were significantly different between mortality and survivor groups. Further χ2 test analysis revealed significant differences in the presenting consciousness disturbance (p = 0.001), place of attack (p = 0.04), and referral transportation (p = 0.008) between these groups. In conclusion, old age, delay between neurologist consultation and ward admission, severity of stroke, and multiple risk factors of CVD are significant risk factors for in-hospital mortality. Conversely, being free of initial consciousness disturbance, living in an urban area, and having direct transportation to a stroke center are protective factors in survivors. The concept of “brain attack” should be re-emphasized among ED physicians. The interconnection between stroke centers and emergency medical systems (EMS) should be more tightly built to promote timely management for hyperacute stroke care.

Background Estrogen is involved in neuron plasticity and can promote neuronal survival in stroke. Its actions are mostly exerted via estrogen receptor alpha (ERα). Previous animal studies have shown that ERα is upregulated by DNA demethylation following ischemic injury. This study investigated the methylation levels in the ERα promoter in the peripheral blood of ischemic stroke patients. Methods The study included 201 ischemic stroke patients, and 217 age- and sex-comparable healthy controls. The quantitative methylation level in the 14 CpG sites of the ERα promoter was measured by pyrosequencing in each participant. Multivariate regression model was used to adjust for stroke traditional risk factors. Stroke subtypes and sex-specific analysis were also conducted. Results The results demonstrated that the stroke cases had a lower ERα methylation level than controls in all 14 CpG sites, and site13 and site14 had significant adjusted p-values of 0.035 and 0.026, respectively. Stroke subtypes analysis showed that large-artery atherosclerosis and cardio-embolic subtypes had significantly lower methylation levels than the healthy controls at CpG site5, site9, site12, site13 and site14 with adjusted p = 0.039, 0.009, 0.025, 0.046 and 0.027 respectively. However, the methylation level for the patients with small vessel subtype was not significant. We combined the methylation data from the above five sites for further sex-specific analysis. The results showed that the significant association only existed in women (adjusted p = 0.011), but not in men (adjusted p = 0.300). Conclusions Female stroke cases have lower ERα methylation levels than those in the controls, especially in large-artery and cardio-embolic stroke subtypes. The study implies that women suffering from ischemic stroke of specific subtype may undergo different protective mechanisms to reduce the brain injury.

Neurologic signs and symptoms are common in acute malarial infection. However, after the parasites have been cleared from the blood and patients recover full consciousness, neurologic or psychiatric symptoms may occur or recur within 2 months after the acute illness. This phenomenon is called “postmalaria neurologic syndrome” (PMNS). We present a 50-year-old man who returned from the Republic of Malawi and soon developed Plasmodium falciparum malaria. Cerebral malaria, renal failure, hepatic failure, diffuse intravascular coagulation with thrombocytopenia, and upper gastrointestinal bleeding were noted during the acute stage. He was admitted to the infectious diseases ward and treated for 3 weeks. He was free from clinical general symptoms and parasites in blood smear when discharged. However, 2 weeks after discharge, he began to experience severe headache, dizziness, diplopia, mild hand tremor, unsteady gait, and easy falling. When readmitted to the neurologic ward, he presented with irritability, delirium, visual hallucination, and strange behavior. Neurologic examination was normal except for mild general weakness and evident truncal ataxia when walking. Brain magnetic resonance imaging revealed no structural lesions, and electroencephalography showed diffuse cortical dysfunction. Cerebral spinal fluid profile exhibited cytoalbuminologic dissociation. Brain single photon emission computed tomography showed diffuse cerebral parenchymal disorder. Nerve conduction studies revealed early sensory predominant polyneuropathy. The unsteadiness persisted for the initial 2 weeks of hospitalization until corticosteroid was administered. Intravenous methylprednisolone (80 mg/day) was continued for 3 days, followed by oral prednisolone (45 mg/day). His unsteadiness improved gradually after medication, and he absconded from the hospital on the 9th day of corticosteroid treatment with clear consciousness and free ambulation. The manifestation of PMNS is diverse and may present as an acute confusional state or psychosis, generalized seizure, fine tremors, cerebellar syndromes, postural hypotension, or malarial polyneuritis. Although the neurologic syndrome is primarily self-limited in most cases, corticosteroid may be beneficial in reversing PMNS.

Cognitive impairment in Parkinson's disease (PD) has been determined to be due to the interruption of frontal-subcortical neural circuits. To evaluate which kind of frontal-subcortical dysfunction may be present and the relationship of this dysfunction with P300 in PD patients, non-demented PD patients and controls were rendered for comprehensive Frontal Test Battery and P300 assessments. PD patients manifested significantly with frontal dysfunction and revealed a good correlation between P300 and executive dysfunction. We conclude that PD patients may manifest with cognitive impairment related to frontal dysfunction, and P300 may be an indicator reflecting the evolution of dysexecutive syndrome.

Although the Blessed Dementia Rating Scale (BDRS), a clinical screening instrument, has been applied extensively, no suitable cut-off values and clinical application have been proposed, particularly in mild cognitive impairment (MCI), the precursor of dementia. The BDRS, Mini Mental State Examination (MMSE), and Clinical Dementia Rating Scale (CDR) were administrated in people aged 65 years and above, who were enrolled from southern Taiwan with multistep stratified random sampling and followed-up for 2 years. All subjects (total number = 3,027), with new onset of MCI (defined as CDR = 0.5) in the first year and dementia (defined as CDR > or = 1) in the second and third years were subjected to statistical analysis. In distinguishing normal from MCI, except in the literate group aged 65-74 years, MMSE was superior to BDRS, with cut-off values of 1 in both literate groups aged 65-74 years and > or = 75 years, and 1.5 and 2 in less educated groups aged 65-74 and > or = 75 years, respectively. In distinguishing MCI from dementia, BDRS had cut-off values of 2.5 in both literate groups aged 65-74 and > or = 75 years, and 2.5 and 3 in less educated groups aged 65-74 and > or = 75 years, respectively. These values were better than those for MMSE in all groups. BDRS might be considered as a better tool than MMSE to screen for MCI and dementia in the increasing proportion of literate elderly aged 65-74 years in the aging population.

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.

Cerebral venous thrombosis (CVT) is not uncommon, but CVT associated with bilateral internal jugular vein stenosis (BIJVS) is rare. Bilateral internal jugular vein stenting is also a rare procedure. We report on a patient with CVT associated with BIJVS, who was treated successfully using direct thrombolysis and bilateral internal jugular vein stenting.

This study aims to clarify the association between apolipoprotein E gene (ApoE) polymorphism, ischemic cerebrovascular diseases (ICVD) and vascular dementia (VaD) in Taiwan Chinese. 277 patients with ICVD, 49 patients with probable VaD and 112 controls were recruited for this study. Distributions of ApoE Ε4 carriers and allele frequencies were 28.5 and 14.5% for patients with ICVD, 20.4 and 10.2% for patients with VaD, whereas these values were 22.9 and 11.6% for controls. Distributions of ApoE Ε2 carriers and allele frequencies were 10.1 and 5.2% for ICVD patients, 6.1 and 3.1% for VaD patients, but 12.5 and 8.0% for controls. There were no differences between ICVD patients and controls, or VaD patients and controls in their Ε4 carriers. Those patients aged 65 and under, carrying the Ε2 allele, had a lower risk of developing ICVD and VaD than did their counterparts. These findings suggest that ApoE Ε4 plays no significant role in the development of ICVD and VaD, but that ApoE Ε2 has a protective effect with regard to the development of ICVD and VaD for Taiwan Chinese below the age of 65.

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.

In an aim to detect the dysfunction of central nervous system among rats with varied durations of hypothyroidism and to elucidate the recovery potential after thyroxine replacement, a series of BAEP were conducted and compared with age-matched controls. BAEP was performed in five groups of the hypothyroid animals 1, 3, 5, 7, and 9 months after thyroidectomy respectively. Following initial electrophysiological assessment, thyroxine replacement was administered to each group of hypothyroid rats, and BAEP was performed at two month intervals, up to two successive normal studies or six months after the initiation of therapy, whichever came first. Before thyroxine treatment, prolonged I-V interpeak latency was the most consistent abnormal finding in all groups of hypothyroid rats, and longer hypothyroid state correlated well with more severe central conduction disorder. Hearing impairment was also noted among those with long duration of hypothyroidism. After thyroxine replacement, the central conduction dysfunction usually returned to normal if the hypothyroid state was not more than 5 months in duration. However, when hypothyroid state persisted over 7 months or more, there would be an incomplete recovery for central conduction disorder. The present study brings out the concept of 'therapeutic window' in reversing the central nervous dysfunction caused by hypothyroidism in adult rats.

To determine the prevalence and subtypes of dementia in southern Taiwan, a two-phase study consisting of a phase I screening survey using the Mini-Mental Status Examination (MMSE) and a phase II diagnostic examination using the CERAD neuropsychological battery and the neurobehavioral examination was conducted. According to the household records, stratified random sampling by the degree of urbanization of the community was used, and 2915 inhabitants aged 65 and over participated in this study. The ICD-10NA criteria for dementia, NINCDS-ADRDA guidelines for Alzheimer's disease (AD), and NINDS-AIREN criteria for vascular dementia (VaD) were employed. Three hundred and ninety-eight persons who had MMSE scores below the cutoff values were recruited into the phase II study, of whom 108 had dementia. The prevalence rate (PR) of dementia was 3.7%, increasing from 1.3% in people 65-69 years old to 16.5% in people 85 years old and older. The age-standardized PR (ASPR) was 4.0%. AD (58 cases, 53.7%, PR=2.0%, ASPR=2.3%) was the most common cause of dementia, followed by VaD (25 cases, 23.1%, PR=0.9%, ASPR=0.9%), and mixed dementia (eight cases, 7.4%). After adjusting for age, sex and education using logistic regression analysis, aging was a significant risk factor for AD, VaD and total dementia. Female sex and illiteracy were significant risk factors for AD only. We concluded that the prevalence of dementia in Taiwan is lower than in the developed countries, which could be due to a relatively young elderly population and a high mortality from dementia in Taiwan. AD is the leading cause of dementia in Taiwan. Considering the high stroke prevalence, the relatively lower prevalence of VaD in Taiwan deserves further investigation.

In order to detect the dysfunction of central and peripheral nervous systems among rats with varied duration of hypothyroidism and to elucidate the pattern of recovery after thyroxine replacement, a series of BAEP and PNCS (Peripheral Nerve Conduction Study) were conducted and compared with age-matched controls. BAEP and PNCS were performed in three groups of hypothyroid animals 1, 3 and 5 months after thyroidectomy, respectively. Following initial electrophysiological assessment, thyroxine replacement was administered to each group of hypothyroid rats, and BAEP and PNCS were performed at two month intervals, up to two successive normal studies, or six months after the initiation of therapy, whichever came first. For BAEP, prolonged I-V interpeak latency was the most consistent abnormal finding in all groups of hypothyroid rats, and longer hypothyroid states correlated well with more severe central conduction disorder. Nevertheless, these abnormalities usually returned to normal after thyroxine replacement if the duration of hypothyroidism was less than 5 months. Regarding PNCS, all groups of thyroidectomized rats showed normal conduction before and after thyroxine therapy. The present study indicates that, in rats: (1) the peripheral nervous system seems to be more resistant to hypothyroidism than the central nervous system, or (2) the pathogenesis of central and peripheral nerve dysfunction in hypothyroid rats may occur through different mechanisms.

Susceptibility weighted imaging (SWI) is a newly developed magnetic resonance (MR) protocol. Recent studies have found that SWI may be useful in the field of cerebrovascular diseases, especially for detecting the presence of prominent veins, microbleeds and the susceptibility vessel sign (SVS). Some authors have even suggested that SWI can be used to predict outcome. We conducted a prospective study of patients hospitalized with middle cerebral artery territory infarction receiving MRI within 2 days of stroke onset. The presence of prominent veins, microbleeds and SVS in SWI was analyzed along with hospital characteristics of the patients. A total of 44 patients were enrolled. Among the 44 patients, 15 (34.1%) patients showed prominent veins, 19 (43.2%) showed SVS, and 14 (31.8%) showed microbleeds. The presence of SVS and prominent veins was not associated with prognosis. Though not statistically significant (p = 0.06), patients with SVS were more likely to develop later brain edema. SVS was significantly associated with arterial occlusion (p = 0.008) based on the MR angiogram, and microbleeds were significantly associated with later hemorrhagic transformation (p = 0.018). In our study, SWI could not be used to predict outcome as previously suggested. However, the presence of microbleeds may predict further hemorrhagic transformation, and the presence of SVS could be used to detect intra-arterial thrombus. Patients with SVS were also more likely to develop later brain edema. Including SWI in routine MR protocols for major acute ischemic stroke would be worthwhile.

BackgroundEstrogen receptor α (ERα) has been shown to protect against atherosclerosis. Methylation of the ERα gene can reduce ERα expression leading to a higher risk for cardiovascular disease. Recently, microRNAs have been found to regulate DNA methyltransferases (DNMTs) and thus control methylation status in several genes. We first searched for microRNAs involved in DNMT-associated DNA methylation in the ERα gene. We also tested whether statin and a traditional Chinese medicine (San-Huang-Xie-Xin-Tang, SHXXT) could exert a therapeutic effect on microRNA, DNMT and ERα methylation.Methodology/principal findingsThe ERα expression was decreased and ERα methylation was increased in LPS-treated human aortic smooth muscle cells (HASMCs) and the aorta from rats under a high-fat diet. MicroRNA-152 was found to be down regulated in the LPS-treated HASMCs. We validated that microRNA-152 can knock down DNMT1 in HASMCs leading to hypermethylation of the ERα gene. Statin had no effect on microRNA-152, DNMT1 or ERα expression. On the contrary, SHXXT could restore microRNA-152, decrease DNMT1 and increase ERα expression in both cellular and animal studies.Conclusions/significanceThe present study showed that microRNA-152 decreases under the pro-atherosclerotic conditions. The reduced microRNA-152 can lose an inhibitory effect on DNA methyltransferase, which leads to hypermethylation of the ERα gene and a decrease of ERα level. Although statin can not reverse these cascade proatherosclerotic changes, the SHXXT shows a promising effect to inhibit this unwanted signaling pathway.