Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post-Stroke Recovery: The CHIMES and CHIMES-E Studies.

BACKGROUND AND PURPOSE: MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. METHODS: Data from the CHInese Medicine NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. RESULTS: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8 ± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0-1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. CONCLUSIONS: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments.

The professional practice and training of neurology in the Asian and Oceanian Region: A cross-sectional survey by the Asian and Oceanian Association of Neurology (AOAN).

OBJECTIVE: To survey AOAN member countries regarding their organizational structure, postgraduate neurology training program, and resources for neurological care provision. METHODOLOGY: A cross-sectional survey using a 36-item questionnaire was conducted among country representatives to AOAN from August 2015 to August 2016. RESULTS: A total of 18/20 AOAN member countries participated in the survey. All the countries have organized association with regular meetings, election of officers and neurology training program. In 9/18 countries, professionals other than neurologists were eligible for affiliation. In 11/18 countries, prior Internal medicine training (or equivalent postgraduate housemanship) is prerequisite to neurology program. Recertification examination is not a practice, but submission of CME is required in 7/18 countries to maintain membership. 12/18 countries publish peer-reviewed journals with at least 1 issue per year. Subspecialty training is offered in 14/18 countries. The ratio of neurologist to population ranges from 1:14,000 to as low as 1:32 million with 9/18 having <1 neurologist per 100,000 population. 6/18 countries have at least 1 specialized center solely for neurological diseases. In government-funded hospitals, the lag time to be seen by a neurologist and/or obtain neuroimaging scan ranges from 1day to 3months. All except one country have several medical- and lay- advocacy or support groups for different neurological conditions. IMPLICATIONS: The data generated can be used for benchmarking to improve neurological care, training, collaborative work and research in the field of neurosciences among the AOAN member countries. The paper presented several strategies used by the different organizations to increase their number of neurologists and improve the quality of training. Sharing of best practices, academic networking, exchange programs and use of telemedicine have been suggested.

Corrigendum to "Alzheimer's Disease Dementia as the Diagnosis Best Supported by the Cerebrospinal Fluid Biomarkers: Difference in Cut-Off Levels from Thai Experience".

[This corrects the article DOI: 10.1155/2012/212063.].

Prognostic Factors and Pattern of Long-Term Recovery with MLC601 (NeuroAiD™) in the Chinese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study.

BACKGROUND: The Chinese Medicine NeuroAiD Efficacy on Stroke recovery - Extension (CHIMES-E) study is among the few acute stroke trials with long-term outcome data. We aimed to evaluate the recovery pattern and the influence of prognostic factors on treatment effect of MLC601 over 2 years. METHODS: The CHIMES-E study evaluated the 2 years outcome of subjects aged ≥18 years with acute ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score 6-14, pre-stroke modified Rankin Scale (mRS) score ≤1 included in a multicenter, randomized, double-blind, placebo-controlled trial of MLC601 for 3 months. Standard stroke care and rehabilitation were allowed during follow-up with mRS score being assessed in-person at month (M) 3 and by telephone at M1, M6, M12, M18 and M24. RESULTS: Data from 880 subjects were analyzed. There was no difference in baseline characteristics between treatment groups. The proportion of subjects with mRS score 0-1 increased over time in favor of MLC601 most notably from M3 to M6, thereafter remaining stable up to M24, while the proportion deteriorating to mRS score ≥2 remained low at all time points. Older age (p < 0.01), female sex (p = 0.06), higher baseline NIHSS score (p < 0.01) and longer onset to treatment time (OTT; p < 0.01) were found to be predictors of poorer outcome at M3. Greater treatment effect, with more subjects improving on MLC601 than placebo, was seen among subjects with 2 or more prognostic factors (OR 1.65 at M3, 1.78 at M6, 1.90 at M12, 1.65 at M18, 1.39 at M24), especially in subjects with more severe stroke or longer OTT. CONCLUSIONS: The sustained benefits of MLC601 over 2 years were due to more subjects improving to functional independence at M6 and beyond compared to placebo. Selection of subjects with poorer prognosis, particularly those with more severe NIHSS score and longer OTT delay, as well as a long follow-up period, may improve the power of future trials investigating the treatment effect of neuroprotective or neurorestorative therapies.

Targeting Netrin-1 in glioblastoma stem-like cells inhibits growth, invasion, and angiogenesis.

Glioblastoma (GBM) is an aggressive malignant brain tumor that still lacks effective therapy. Glioblastoma stem cells (GBM-SCs) were identified to contribute to aggressive phenotypes and poor clinical outcomes for GBM. Netrin-1, an axon guidance molecule, has been found in several tumors in adults. However, the role of Netrin-1 in GBM-SCs remains largely unknown. In this study, CD133-positive U251 GBM cells were used as a putative GBM-SC population to identify the functions of Netrin-1. Using lentiviral transduction, Netrin-1 miR RNAi vectors were transduced into CD133-positive U251 cells. We demonstrated that cell proliferation and survival were decreased following targeted deletion of Netrin-1. Cell invasion was dramatically diminished in Netrin-1 knockdown GBM-SCs. Moreover, Netrin-1 knockdown GBM-SCs exhibited less proangiogenic activity. In conclusion, Netrin-1 may represent a therapeutic target in glioblastoma.

Stroke burden and stroke care system in Asia.

BACKGROUND: Stroke is a major cause of death and disability. Asia is the largest and mostly populated continent of the world. The Asian Stroke Advisory Panel (ASAP) consists of stroke neurologists from 12 different countries in 13 Asian regions. It has been established for 17 years, and holds regular meetings for reviewing the stroke activities in Asia. It also helps in conducting several multinational research projects. This study is one of the ASAP projects and aims to explore stroke care systems in member countries in Asia. METHODS: The survey is categorized into five main parts including the general country information, stroke epidemiology, stroke risk factors, stroke care systems, and national stroke professional societies. RESULTS: A higher proportion of ischemic stroke in comparison to hemorrhagic stroke was found in all countries. The overall incidence of stroke in Asia is between 116 and 483/100,000 per year.When compared to 1999, a 2-3-fold increase in the number of neurologists was observed in all countries. CONCLUSIONS: There is a favorable trend in all Asian countries regarding the need to increase the number of neurologists and facilities to effectively administer stroke care.

CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy.

BACKGROUND: The CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) study was an international randomized double-blind placebo-controlled trial of MLC601 (NeuroAiD) in subjects with cerebral infarction of intermediate severity within 72 h. CHIMES-E (Extension) aimed at evaluating the effects of the initial 3-month treatment with MLC601 on long-term outcome for up to 2 years. METHODS: All subjects randomized in CHIMES were eligible for CHIMES-E. Inclusion criteria for CHIMES were age ≥18, baseline National Institute of Health Stroke Scale of 6-14, and pre-stroke modified Rankin Scale (mRS) ≤1. Initial CHIMES treatment allocation blinding was maintained, although no further study treatment was provided in CHIMES-E. Subjects received standard care and rehabilitation as prescribed by the treating physician. mRS, Barthel Index (BI), and occurrence of medical events were ascertained at months 6, 12, 18, and 24. The primary outcome was mRS at 24 months. Secondary outcomes were mRS and BI at other time points. RESULTS: CHIMES-E included 880 subjects (mean age 61.8 ± 11.3; 36% women). Adjusted OR for mRS ordinal analysis was 1.08 (95% CI 0.85-1.37, p = 0.543) and mRS dichotomy ≤1 was 1.29 (95% CI 0.96-1.74, p = 0.093) at 24 months. However, the treatment effect was significantly in favor of MLC601 for mRS dichotomy ≤1 at 6 months (OR 1.49, 95% CI 1.11-2.01, p = 0.008), 12 months (OR 1.41, 95% CI 1.05-1.90, p = 0.023), and 18 months (OR 1.36, 95% CI 1.01-1.83, p = 0.045), and for BI dichotomy ≥95 at 6 months (OR 1.55, 95% CI 1.14-2.10, p = 0.005) but not at other time points. Subgroup analyses showed no treatment heterogeneity. Rates of death and occurrence of vascular and other medical events were similar between groups. CONCLUSIONS: While the benefits of a 3-month treatment with MLC601 did not reach statistical significance for the primary endpoint at 2 years, the odds of functional independence defined as mRS ≤1 was significantly increased at 6 months and persisted up to 18 months after a stroke.

Stroke awareness and factors influencing hospital arrival time: a prospective observational study.

BACKGROUND: Data concerning stroke awareness and factors associated with time of hospital arrival for acute stroke patients in Thailand are still lacking. OBJECTIVE: To assess stroke awareness and to identify factors influencing hospital arrival time after an acute stroke. MATERIAL AND METHOD: This is aprospective study comprising consecutive acute stroke patients admitted in Siriraj Hospital, Bangkok, Thailand between August 2010 and December 2011. Demographic data, stroke severity using the NIHSS, diagnosis and stroke awareness questionnaire were collected. RESULTS: Of 217 acute stroke patients, mean age was 66 ± 13.7 years. Mean stroke severity was 10 ± 7.6. Patients arrived at the Emergency Department within 4.5 hours (early hospital arrival: EHA) in 38.2% of the cases, 16.6% by ambulance. Only 34.6% of patients recognized that they were having stroke. Factors associated with EHA were 1) stroke awareness (OR 1.96, 95% CI 1.07-3.60, p = 0.030), 2) arrival by ambulance (OR 2.23, 95% CI 1.03-4.81, p = 0.042), and 3) NIHSS >15 (OR 2.26, 95% CI 1.17-4.35, p = 0.015). CONCLUSION: Only one-third of patients were aware of stroke symptoms. Only one in six patients used emergency transportation. Public educational campaign is needed to increase the community awareness of stroke warning symptoms and the urgent emergency medical services.

Dual small-molecule targeting of SMAD signaling stimulates human induced pluripotent stem cells toward neural lineages.

Incurable neurological disorders such as Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD) are very common and can be life-threatening because of their progressive disease symptoms with limited treatment options. To provide an alternative renewable cell source for cell-based transplantation and as study models for neurological diseases, we generated induced pluripotent stem cells (iPSCs) from human dermal fibroblasts (HDFs) and then differentiated them into neural progenitor cells (NPCs) and mature neurons by dual SMAD signaling inhibitors. Reprogramming efficiency was improved by supplementing the histone deacethylase inhibitor, valproic acid (VPA), and inhibitor of p160-Rho associated coiled-coil kinase (ROCK), Y-27632, after retroviral transduction. We obtained a number of iPS colonies that shared similar characteristics with human embryonic stem cells in terms of their morphology, cell surface antigens, pluripotency-associated gene and protein expressions as well as their in vitro and in vivo differentiation potentials. After treatment with Noggin and SB431542, inhibitors of the SMAD signaling pathway, HDF-iPSCs demonstrated rapid and efficient differentiation into neural lineages. Six days after neural induction, neuroepithelial cells (NEPCs) were observed in the adherent monolayer culture, which had the ability to differentiate further into NPCs and neurons, as characterized by their morphology and the expression of neuron-specific transcripts and proteins. We propose that our study may be applied to generate neurological disease patient-specific iPSCs allowing better understanding of disease pathogenesis and drug sensitivity assays.

Factors predicting high estimated 10-year stroke risk: thai epidemiologic stroke study.

BACKGROUND: The purpose of the study was to determine the factors predicting high estimated 10-year stroke risk based on a risk score, and among the risk factors comprising the risk score, which factors had a greater impact on the estimated risk. METHODS: Thai Epidemiologic Stroke study was a community-based cohort study, which recruited participants from the general population from 5 regions of Thailand. Cross-sectional baseline data of 16,611 participants aged 45-69 years who had no history of stroke were included in this analysis. Multiple logistic regression analysis was used to identify the predictors of high estimated 10-year stroke risk based on the risk score of the Japan Public Health Center Study, which estimated the projected 10-year risk of incident stroke. RESULTS: Educational level, low personal income, occupation, geographic area, alcohol consumption, and hypercholesterolemia were significantly associated with high estimated 10-year stroke risk. Among these factors, unemployed/house work class had the highest odds ratio (OR, 3.75; 95% confidence interval [CI], 2.47-5.69) followed by illiterate class (OR, 2.30; 95% CI, 1.44-3.66). Among risk factors comprising the risk score, the greatest impact as a stroke risk factor corresponded to age, followed by male sex, diabetes mellitus, systolic blood pressure, and current smoking. CONCLUSIONS: Socioeconomic status, in particular, unemployed/house work and illiterate class, might be good proxy to identify the individuals at higher risk of stroke. The most powerful risk factors were older age, male sex, diabetes mellitus, systolic blood pressure, and current smoking.

Quality of acute ischemic stroke care in Thailand: a prospective multicenter countrywide cohort study.

BACKGROUND: Data concerning quality of acute stroke care and outcome are scarce in developing countries. OBJECTIVE: This study aimed to evaluate quality of acute stroke care and stroke outcomes in Thailand. METHODS: We performed a multicenter countrywide prospective cohort study. Consecutive patients with an acute ischemic stroke admitted to the participating institutions between June 2008 and November 2010 were included. Baseline characteristics, process measures including thrombolysis use, acute stroke unit admission, initiation of aspirin within 48 hours, and antithrombotic and/or anticoagulation medication at discharge were recorded. Main outcome measures were death and disability at discharge as well as in-hospital complications. RESULTS: A total of 1222 patients were included with a mean (±SD) age of 65.0 ± 13 years, and 55.0% were men. Median National Institutes of Health Stroke Scale score was 6.5. Patients were given aspirin within 48 hours, admitted to acute stroke unit, and given thrombolytic therapy in 71.1%, 24.6%, and 3.8%, respectively. Good recovery at discharge (modified Rankin scale score 0-1) was found in 26.1%, and 3.2% of patients died during hospitalization. The median length of stay was 4 days. Factors predicting poor outcome (modified Rankin scale score 5-6) at discharge included: age (by 10-year increments: adjusted odds ratio [OR] 1.23; 95% confidence interval [CI], 1.06-1.43), female sex (adjusted OR 1.52; 95% CI, 1.05-2.19), initial National Institutes of Health Stroke Scale score (adjusted OR 1.35; 95% CI, 1.27-1.43), and in-hospital complications (adjusted OR 3.16; 95% CI, 1.58-6.35). CONCLUSIONS: Limited access to acute ischemic stroke care interventions were observed in many domains especially thrombolysis and stroke unit admission. These findings emphasize an urgent need for strategies to improve standard acute stroke care among developing countries.

Chinese medicine neuroaid efficacy on stroke recovery: a double-blind, placebo-controlled, randomized study.

BACKGROUND AND PURPOSE: Previous clinical studies suggested benefit for poststroke recovery when MLC601 was administered between 2 weeks and 6 months of stroke onset. The Chinese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study tested the hypothesis that MLC601 is superior to placebo in acute, moderately severe ischemic stroke within a 72-hour time window. METHODS: This multicenter, double-blind, placebo-controlled trial randomized 1100 patients with a National Institutes of Health Stroke Scale score 6 to 14, within 72 hours of onset, to trial medications for 3 months. The primary outcome was a shift in the modified Rankin Scale. Secondary outcomes were modified Rankin Scale dichotomy, National Institutes of Health Stroke Scale improvement, difference in National Institutes of Health Stroke Scale total and motor scores, Barthel index, and mini-mental state examination. Planned subgroup analyses were performed according to age, sex, time to first dose, baseline National Institutes of Health Stroke Scale, presence of cortical signs, and antiplatelet use. RESULTS: The modified Rankin Scale shift analysis-adjusted odds ratio was 1.09 (95% confidence interval, 0.86-1.32). Statistical difference was not detected between the treatment groups for any of the secondary outcomes. Subgroup analyses showed no statistical heterogeneity for the primary outcome; however, a trend toward benefit in the subgroup receiving treatment beyond 48 hours from stroke onset was noted. Serious and nonserious adverse events rates were similar between the 2 groups. CONCLUSIONS: MLC601 is statistically no better than placebo in improving outcomes at 3 months when used among patients with acute ischemic stroke of intermediate severity. Longer treatment duration and follow-up of participants with treatment initiated after 48 hours may be considered in future studies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00554723.

Reliability and validity of the Canadian neurological scale, Thai version.

BACKGROUND: The Canadian Neurological Scale (CNS) is one of the most reliable stroke severity assessment scales. There is a strong need for a simple and well validated stroke severity assessment scale among Thais. OBJECTIVE: To translate and perform a reliability and validity study of the Canadian Neurological Scale, Thai version (CNS-T). MATERIAL AND METHOD: Forward and backward translations of the original CNS version were independently performed. The final version of the CNS-T was prospectively tested for reliability and validity in acute ischemic stroke setting. Consecutive series of acute stroke patients were assessed by one of the six raters from three different types of healthcare providers: 2 stroke nurses, 2 internal medicine residents and 2 stroke fellows. Each patient was independently assessed twice at 3 weeks interval using video tape by all raters. Extent of infarction was measured by MRI lesion volume. Clinical outcome at 3 months was measured using modified Rankin Score (mRS). Correlation among the CNS-T and 3-mo mRS and MRI lesion volume were assessed. Inter and intra-observer reliabilities were evaluated. RESULTS: A total of 38 patients were enrolled. Median CNS-T was 8.5. Intra-observer reliability demonstrated a high agreement with an intraclass correlation (ICC) of 0.99, 0.97, 0.98, 0.96, 0.93 and 0.98 for 2 stroke fellows, 2 internal medicine residents and 2 stroke nurses respectively. Inter-observer reliability between the 6 raters was excellent: ICC 0.87 (95% CI; 0.81-0.92). The Spearman rank correlation coefficient was -0.55 (p = 0.001) between the initial CNS-T score versus initial MRI lesion volume and -0.61 (p < 0.001) between the initial CNS-T score versus 3-mo mRS. CONCLUSION: The CNS-T can be performed by trained nurses, internists and neurologists with an excellent reliability. The CNS-T is a valid and simple clinical tool for stroke severity assessment among Thais.

CHIMES-I: sub-group analyzes of the effects of NeuroAiD according to baseline brain imaging characteristics among patients randomized in the CHIMES study.

RATIONALE: The clinical effects of neuroprotective and/or neurorestorative therapies may vary according to location and size of the ischemic injury. Imaging techniques can be useful in stratifying patients for trials that may be beneficial against particular ischemic lesion characteristics. AIM: To test the hypothesis that the efficacy of NeuroAiD compared with placebo in improving functional outcome and reducing neurological deficit in patients with cerebral infarction of intermediate severity varies between sub-groups of patients randomized in the main Chinese Medicine Neuroaid Efficacy on Stroke study when categorized according to baseline imaging characteristics. DESIGN: This is a retrospective cohort sub-group analysis of patients who participated in the main Chinese Medicine Neuroaid Efficacy on Stroke study, a multicenter, double-blind, placebo-controlled trial that recruited 1100 patients within 72 h of ischemic stroke onset with National Institutes of Health Stroke Scale 6-14 and were randomized to either NeuroAiD or placebo taken four capsules three times daily for three months. Review of the baseline images to classify the acute stroke lesions in terms of size, location, and extent of involvement will be performed retrospectively by two readers who will remain blinded as to treatment allocation and outcomes of the subjects. STUDY OUTCOMES: The primary efficacy end-point in the main Chinese Medicine Neuroaid Efficacy on Stroke study is the modified Rankin Scale grades at three-months. Secondary efficacy end-points are the National Institutes of Health Stroke Scale score at three-months; difference of National Institutes of Health Stroke Scale scores between baseline and 10 days and between baseline and three-months; difference of National Institutes of Health Stroke Scale sub-scores between baseline and 10 days and between baseline and three-months; modified Rankin Scale at 10 days, one-month, and three-months; Barthel index at three-months; and Mini Mental State Examination at 10 days and three-months. Analysis of these primary and secondary end-points will be performed for sub-groups defined in this study after review of the baseline brain imaging: nonlacunar and lacunar, cortical and sub-cortical, hemispheric vs. brainstem, Alberta Stroke Program Early CT score <7 and 7-10, and score <8 and 8-10.

The Dementia and Disability Project in Thai Elderly: rational, design, methodology and early results.

BACKGROUND: A strong inverse relationship of functional limitation and socioeconomic status has been established in western ageing society. Functional limitation can be related to chronic diseases, disuse, cognitive decline, and ageing. Among chronic diseases in the Thai population, cerebrovascular diseases, diabetes, and arthritis are common. These factors are known to contribute to disability and poor quality of life in the elder population. Neuropsychiatric problems, cognitive decline, dementia, and cultural issues in elderly people also can alter the quality of life of the elderly. METHODS: The Dementia and Disability Project in Thai Elderly (DDP) aims at comprehensively assessing community dwelling Thai elderly to understand the relationship between disability and motor function, neuropsychiatric symptoms, cognitive function, and chronic diseases. The DDP is the first study to look at the prevalence and etiology of dementia and of mild cognitive impairment (MCI) in Thai elders and to explore the relationship of cognition, disability, small vessel diseases and cortical degeneration with neuroimaging in Thai elderly people. 1998 Thai elders were screened in 2004-2006 and diagnosed as having MCI or dementia. 223 elders with MCI or dementia and cognitively normal elderly had brain magnetic resonance imaging (MRI) or at baseline. 319 elders from the 3 groups had blood tests to investigate the risks and possible etiologies of dementia including genotyping at baseline. RESULTS: The mean age of elders in this study is 69.51(SD=6.71, min=60, max=95) years. 689(34.9%) are men and 1284(65.1%) are women. Mean body weight was 58.36(SD=11.20) kgs. The regression model reveals that performance on gait and balance and serum triglyceride predicts activity of daily living performance (adjusted r2 = 0.280, f=2.644, p=0.003). The majority of abnormal gait in Thai elders was lower level gait disturbance. Only 1.5% (29/1952) had highest level gait disorders. 39.5% of 1964 subjects were free of chronic diseases. Treatment gap (indicating those who have untreated or inadequate treatment) of diabetes mellitus and hypertension in Thai elders in this study was 37% and 55.5% respectively. 62.6% of Thai elders have ApoE3E3 allele. Prevalence of positive ApoE4 gene in this study is 22.85%. 38.6% of Thai elders who had MRI brain study have moderate to severe white matter lesions. CONCLUSION: The large and comprehensive set of measurements in DDP allows a wide-ranging explanation of the functional and clinical features to be investigated in relation to white matter lesions or cortical atrophy of the brain in Thai elderly population. An almost 2 year follow up was made available to those with MCI and dementia and some of the cognitively normal elderly. The longitudinal design will provide great understanding of the possible contributors to disability in the elderly and to the progression of cognitive decline in Thai elders.

Risk of metabolic syndrome for stroke is not greater than the sum of its components: Thai Epidemiologic Stroke (TES) study.

Limited information is available on the association between the metabolic syndrome (MetS) and stroke. Whether or not MetS confers a risk greater than the sum of its components is controversial. This study aimed to assess the association of MetS with stroke, and to evaluate whether the risk of MetS is greater than the sum of its components. The Thai Epidemiologic Stroke (TES) study is a community-based cohort study with 19,997 participants, aged 45-80 years, recruited from the general population from 5 regions of Thailand. Baseline survey data were analyzed in cross-sectional analyses. MetS was defined according to criteria from the National Cholesterol Education Program (NCEP) Adult Treatment Panel III, the American Heart Association/National Heart, Lung, and Blood Institute (revised NCEP), and International Diabetes Federation (IDF). Logistic regression analysis was used to estimate association of MetS and its components with stroke. Using c statistics and the likelihood ratio test we compared the capability of discriminating participants with and without stroke of a logistic model containing all components of MetS and potential confounders and a model also including the MetS variable. We found that among the MetS components, high blood pressure and hypertriglyceridemia were independently and significantly related to stroke. MetS defined by the NCEP (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.32-2.04), revised NCEP (OR, 2.27; 95% CI, 1.80-2.87), and IDF definitions (OR, 1.70; 95% CI, 1.37-2.13) was significantly associated with stroke after adjustment for age, sex, geographical area, education level, occupation, smoking status, alcohol consumption, and low-density lipoprotein cholesterol. After additional adjustment for all MetS components, these associations were not significant. There were no statistically significant difference (P=.723-.901) in c statistics between the model containing all MetS components and potential confounders and the model also including the MetS variable. The likelihood ratio test also showed no statistically significant (P=.166-.718) difference between these 2 models. Our findings suggest that MetS is associated with stroke, but not to a greater degree than the sum of its components. Thus, the focus should be on identification and appropriate control of its individual components, particularly high blood pressure and hypertriglyceridemia, rather than of MetS itself.

Etiology and risk factors of stroke in HIV-infected patients in Siriraj Hospital: a case-control study.

BACKGROUND: Stroke and HIV infection are major health problems in Thailand. There is limited data regarding the etiology and risk factors of stroke in HIV-infected Thai patients. OBJECTIVE: To study the risk factors, types, and mechanisms of stroke in HIV-infected patients. MATERIAL AND METHOD: The authors reviewed records of consecutive HIV-infected patients with acute first stroke in a large urban medical center from August 1, 2009 through December 31, 2010. Age-matched controls of HIV-infected patients without stroke were consecutively recruited at a 2:1 ratio. Data collection included demographics, stroke subtypes, risk factors of stroke, and HIV disease parameters. Multiple logistic regression analysis (p < 0.05) identified factors associated with stroke in HIV-infected patients. RESULTS: There were 37 subjects and 74 controls. In HIV-positive stroke patients, 81.1% were males and mean age was 50.5 years. There were 33 and 4 cases of ischemic and hemorrhagic strokes respectively. HIV infection was previously diagnosed in 70%, mean CD4 count was 287 cells/uL and 33% had CD4 counts < 200 cells/uL. Prior antiretroviral medications were used in 49%. TOAST classification of stroke was as follows: large artery atherosclerosis 2 (6.1%), small vessel occlusion 9 (27.3%), cardioembolism 2 (6.1%), other determined etiology 9 (27.3%) (vertebral artery dissection 1, anti-thrombin III deficiency 1, thrombotic thrombocytopenic purpura 1, tuberculous meningitis 4, cryptococcal meningitis 1, intravenous heroin 1) and undetermined 11 (33.2%) (incomplete evaluation 10, negative evaluation 1). Multivariate analysis demonstrated the following to be significant risk factors of stroke: smoking p = 0.001, adjusted OR 6.9 (95% CI 12.3, 21.1) and tuberculous meningitis p = 0.034, adjusted OR 11.9 (95% CI 1.2, 117.2). CONCLUSION: Stroke etiology in HIV-infected patients is more heterogeneous than in non-immunocompromised hosts. Smoking and concurrent tuberculous meningitis were significantly associated with stroke in HIV-infected Thai patients. Further prospective cohort studies should be performed in a larger population of more severely immunocompromised patients in Thailand.

Siriraj Acute Stroke Unit: 10 years experience.

BACKGROUND: Stroke is the second most common cause of death and leading cause of adult disability worldwide. The recent publication guidelines suggest that there are treatment strategies for optimizing the management of acute stroke patients including thrombolytic therapy, antiplatelet drugs and the establishment of a stroke unit. In Thailand, the first stroke unit has been established since May 1997 and was named Siriraj Acute Stroke Unit (SASU). MATERIAL AND METHOD: The authors retrospectively analyzed the data of stroke patients who were admitted in the SASU from May 1997 to May 2007, as well as hyper acute stroke (within 3 hours after onset). The statistical analysis was performed by using SPSS 11.0. RESULTS: There were 2,109 patients admitted to the SASU during 10 year-period. The mean age of all patients was 65.35 years (range 14-94 years, median 69.2 years). Stroke subtypes were classified as infarction (including transient ischemic attack) in 1799 patients (86.7%) and hemorrhage in 310 patients (13.26%). The most common stroke mechanism was small vessel disease (38.97%). The mainly ischemic stroke distribution was middle cerebral artery territory (77.14%). Risk factors of stroke were as follow: hypertension (61.79%), diabetes mellitus (35.47%), hyperlipidaemia (46.58%), smoking (21.02%) and prior stroke or coronary heart disease (23.74%). Mortality rate was 3.4% mainly due septicemia (26 patients). The mean total hospital stay of stroke patients at the SASU was 13.81 days (ranging from 1-120 days). There were thirty hyper-acute ischemic stroke patients who received intravenous thrombolytic therapy (between August 2005 and May 2007) for which the mean age was 70.7 years (ranges 48-88 years, median 74.5 years). Mean initial National Institutes of Health Stroke Scale (NIHSS) was 14.27. Intracranial hemorrhage after intravenous thrombolytic therapy was found in 8 patients which include 3 patients with symptomatic hemorrhage. CONCLUSION: The standard of care in SASU is not inferior to other stroke unit worldwide. Admission of acute stroke patient to the SASU provides a better chance of survival as well as a shorter length of hospital stay.

Extensive bilateral ischemic stroke after platelet transfusion in thrombotic thrombocytopenic purpura (TTP): a case report.

A 36-year-old woman presented with abdominal pain followed by fever, confusion, right sided weakness and nuchal rigidity. The investigation showed severe anemia, thrombocytopenia and left middle cerebral artery (MCA) territory infarction. The platelet was given before the lumbar puncture. After that, the patient's clinical was deteriorating to quadriplegia and stuporous. Then the patient was referred to Siriraj Hospital. The patient was diagnosed thrombotic thrombocytopenic purpura (TTP) following pentad of clinical features: microangiopathic hemolytic anemia, thrombocytopenia, fever neurologic, and renal abnormalities. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of brain showed extensive bilateral MCA and mid basilar artery stenosis. That was uncommon findings in TTP. The authors believed that platelet transfusion made the clinical deterioration and develop extensive intracranial vessels stenosis. Even the plasma exchange was performed but the neurological symptoms did not improved. Finally, the patient succumbed from ventilator associated pneumonia at 2 months after diagnosis.

Assessment of cerebrospinal fluid (CSF) beta-amyloid (1-42), phosphorylated tau (ptau-181) and total Tau protein in patients with Alzheimer's disease (AD) and other dementia at Siriraj Hospital, Thailand.

BACKGROUND: The combination of decreased cerebrospinal fluid (CSF) levels of beta-amyloid (1-42) and increased levels of phosphorylated tau (ptau-181) or total tau protein are known to be biomarkers ofAlzheimer's disease (AD). These biomarkers can also be used as predictors of disease progression in persons with mild cognitive impairment. Utilizing biomarkers to differentiate Alzheimer's disease (AD) against non-Alzheimer dementia (non-AD) needs to be explored. OBJECTIVE: To evaluate the clinical use ofCSF biomarker: beta-amyloid (1-42), phosphorylated tau (ptau-181) and total tau protein for distinguishing Alzheimer's disease (AD) from non-Alzheimer dementia (non-AD) in Thai patients. MATERIAL AND METHOD: Thirty patients diagnosed of dementia during 2005-2007 at Siriraj hospital were offered CSF analysis for beta-amyloid (1-42), phosphorylated tau (ptau-181) and total tau protein. Diagnosis of dementia was performed by a concensus diagnostic group utilizing a standard criteria for diagnosis of AD and other dementia. All CSF testing was performed by Enzyme-Linked Immunoassay (ELISA) technique of the INNOTESTM to analyze these biomarkers. RESULTS: Thirty demented patients were recruited in the study. Fourteen had AD and 16 had non-AD including 5 vascular dementia, 5 normal pressure hydrocephalus, 4 frontotemporal lobar degeneration and others. Mean age of the AD group was 67.79 (12.30) and that of non-AD group was 65.75 (15.04). Twelve AD had decreased levels of CSF /3-amyloid (1-42) (less than 487 pg/ml). Only one patient with AD had increased CSF phosphorylated tau (ptau-181) (more than 61 pg/ml). None of theAD patient had increased CSF total tau (more than 425 pg/ml). Eight patients with non-AD had decreased levels of CSF p-amyloid (1-42), one had increased CSF total tau protein, and none had increased CSF phosphorylated tau (ptau-181) protein. The sensitivity of decreased level of CSF beta-amyloid (1-42) in AD against non-AD dementia was 85.71%. Those of increased CSF total tau and phosphorylated tau (ptau-181) protein in AD against non-AD dementia were 7.14% and 0% consecutively. The specificity of decreased level of CSF beta-amyloid (1-42) in AD against non-AD dementia was 50%. The specificity of increased CSF total tau and phosphorylated tau (ptau-181) protein in AD against non-AD dementia were 100% and 93.75% sequentially. The combination of 2 biomarkers would increase specificity but decrease sensitivity. CONCLUSION: CSF biomarker analysis should be encouraged to use as diagnostic aid in memory clinic especially to help diagnosis of atypical presentation of AD. The usefulness of longitudinal data needs to be explored.