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Fulltext Clinical profile, risk factors and aetiology of young ischaemic stroke patients in Asia: A prospective, multicentre, observational, hospital-based study in eight cities

Kay, Sin Tan, Navarro, Jose C, Ka, Sing Wong, Yi, Ning Huang, Hou, Chang Chiu, Poungvarin, Niphon, et al.

Neurology Asia, 2014;19(2):117-127.
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Background and Objective: There is a lack of international collaborative studies on young adults with ischaemic stroke in Asia. The aim of this study was to investigate risk factors, aetiology and outcome at hospital discharge of these patients across 8 participating countries in Asia. Methods: This was a prospective, observational, multicentre, hospital based cohort study. Consecutive young stroke patients with confirmed cerebral infarction between the ages of 18-49 were recruited from December 2011 to May 2012. Data was collected for patient demography, risk factors, investigations, clinical profile and TOAST classification. Outcome measures were death and independence (modified Rankin score≤ 2) at hospital discharge. Results: Two hundred and eighteen patients with the mean age was 40.8±6.7 years were recruited. There was a larger proportion of male patients with a ratio of 1.9:1. Traditional risk factors observed were hypertension (n=103; 47.3%), dyslipidaemia (n=93; 42.4%), smoking (n=85; 38.8%), diabetes (n=53; 24.3%), alcohol use (n=33; 15.0%), a previous history of stroke and transient ischaemic attacks (6.4%), family history (n=12; 5.5%), migraine (n=6;2.8%), pregnancy related (n=5; 2.3%) and numerous cardiac risk factors (0.9-5.5%). The majority suffered arterial infarction; n=216 (99.4%) while n=2 (0.6%) had venous strokes. The predominant stroke subtypes were large artery atherosclerosis (LAA); 29.8% and small vessel occlusion (SVO); 20.2%. LAA and SVO accounted for 37.5% of all stroke subtypes in the ≤36 year age-group. Cardioembolism (15.1%) and stroke of determined aetiology (14.7%) contributed to the other categories of identified stroke subtypes. Mortality on hospital discharge was 3.1% while 65.1% of patients were independent on discharge. Conclusion: This study demonstrated the substantial presence of premature atherosclerosis and conventional risk factors in young ischaemic stroke patients from 8 Asian cities. Venous infarction from cerebral venous thrombosis was rare in this study. Outcome on hospital discharge was poorer compared to Western studies. Detection of vascular risk factors and primary prevention measures should be initiated during late adolescence or early adulthood in urban Asia.
Fulltext Stroke Epidemiology in South, East, and South-East Asia: A Review

Venketasubramanian N, Yoon BW, Pandian J, Navarro JC

J Stroke, 2017 Sep;19(3):286-294.
PMID: 29037005 DOI: 10.5853/jos.2017.00234

Asia, which holds 60% of the world's population, comprises some developing countries which are in economic transition. This paper reviews the epidemiology of stroke in South, East and South-East Asia. Data on the epidemiology of stroke in South, East, and South-East Asia were derived from the Global Burden of Disease study (mortality, disability-adjusted life-years [DALYs] lost because of stroke), World Health Organization (vascular risk factors in the community), and publications in PubMed (incidence, prevalence, subtypes, vascular risk factors among hospitalized stroke patients). Age- and sex-standardized mortality is the lowest in Japan, and highest in Mongolia. Community-based incidence data of only a few countries are available, with the lowest rates being observed in Malaysia, and the highest in Japan and Taiwan. The availability of prevalence data is higher than incidence data, but different study methods were used for case-finding, with different age bands. For DALYs, Japan has the lowest rates, and Mongolia the highest. For community, a high prevalence of hypertension is seen in Mongolia and Pakistan; diabetes mellitus in Papua New Guinea, Pakistan, and Mongolia; hypercholesterolemia in Japan, Singapore, and Brunei; inactivity in Malaysia; obesity in Brunei, Papua New Guinea, and Mongolia; tobacco smoking in Indonesia. Hypertension is the most frequent risk factor, followed by diabetes mellitus and smoking. Ischemic stroke occurs more frequently than hemorrhagic stroke, and subarachnoid hemorrhages are uncommon. There are variations in the stroke epidemiology between countries in South, East, and South-East Asia. Further research on stroke burden is required.
Fulltext A systematic-search-and-review of registered pharmacological therapies investigated to improve neuro-recovery after a stroke

Lee TH, Uchiyama S, Kusuma Y, Chiu HC, Navarro JC, Tan KS, et al.

Front Neurol, 2024;15:1346177.
PMID: 38356890 DOI: 10.3389/fneur.2024.1346177

BACKGROUND: Stroke burden is largely due to long-term impairments requiring prolonged care with loss of productivity. We aimed to identify and assess studies of different registered pharmacological therapies as treatments to improve post-stroke impairments and/or disabilities.
METHODS: We performed a systematic-search-and-review of treatments that have been investigated as recovery-enhancing or recovery-promoting therapies in adult patients with stroke. The treatment must have received registration or market authorization in any country regardless of primary indication. Outcomes included in the review were neurological impairments and functional/disability assessments. "The best available studies" based on study design, study size, and/or date of publication were selected and graded for level of evidence (LOE) by consensus.
RESULTS: Our systematic search yielded 7,801 citations, and we reviewed 665 full-text papers. Fifty-eight publications were selected as "the best studies" across 25 pharmacological classes: 31 on ischemic stroke, 21 on ischemic or hemorrhagic stroke, 4 on intracerebral hemorrhage, and 2 on subarachnoid hemorrhage (SAH). Twenty-six were systematic reviews/meta-analyses, 29 were randomized clinical trials (RCTs), and three were cohort studies. Only nimodipine for SAH had LOE A of benefit (systematic review and network meta-analysis). Many studies, some of which showed treatment effects, were assessed as LOE C-LD, mainly due to small sample sizes or poor quality. Seven interventions had LOE B-R (systematic review/meta-analysis or RCT) of treatment effects.
CONCLUSION: Only one commercially available treatment has LOE A for routine use in stroke. Further studies of putative neuroprotective drugs as adjunctive treatment to revascularization procedures and more confirmatory trials on recovery-promoting therapies will enhance the certainty of their benefit. The decision on their use must be guided by the clinical profile, neurological impairments, and target outcomes based on the available evidence.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376973, PROSPERO, CRD42022376973.
Fulltext Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post-Stroke Recovery: The CHIMES and CHIMES-E Studies

Suwanwela NC, Chen CLH, Lee CF, Young SH, Tay SS, Umapathi T, et al.

Cerebrovasc Dis, 2018;46(1-2):82-88.
PMID: 30184553 DOI: 10.1159/000492625

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.