Sombat Muengtaweepongsa

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.

Effects of MLC601 on Early Vascular Events in Patients After Stroke The CHIMES Study

Background and Purpose— Early vascular events are an important cause of morbidity and mortality in the first 3 months after a stroke. We aimed to investigate the effects of MLC601 on the occurrence of early vascular events within 3 months of stroke onset. Methods— Post hoc analysis was performed on data from subjects included in the CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study, a randomized, placebo-controlled, double-blinded trial that compared MLC601 with placebo in 1099 subjects with ischemic stroke of intermediate severity in the preceding 72 hours. Early vascular events were defined as a composite of recurrent stroke, acute coronary syndrome, and vascular death occurring within 3 months of stroke onset. Results— The frequency of early vascular events during the 3-month follow-up was significantly less in the MLC601 group than in the placebo group (16 [2.9%] versus 31 events [5.6%]; risk difference=−2.7%; 95% confidence interval, −5.1% to −0.4%; P=0.025) without an increase in nonvascular deaths. Kaplan–Meier survival analysis showed a difference in the risk of vascular outcomes between the 2 groups as early as the first month after stroke (Log-rank P=0.024; hazard ratio, 0.51; 95% confidence interval, 0.28–0.93). Conclusions— Treatment with MLC601 was associated with reduced early vascular events among subjects in the CHIMES study. The mechanisms for this effect require further study. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00554723.

Outcomes of Intravenous Thrombolytic Therapy for Acute Ischemic Stroke With an Integrated Acute Stroke Referral Network: Initial Experience of a Community-Based Hospital in a Developing Country

Some of the literature encourages the use of intravenous (IV) thrombolytic therapy for acute ischemic stroke (AIS) in centers with no previous experience with this therapy. The benefits of an acute stroke referral network for IV thrombolytic therapy remain controversial, however. We present outcomes of IV thrombolytic therapy for AIS with an integrated acute stroke referral network at an institution with no previous experience in stroke thrombolysis and compare the results with previously published data. A total of 458 patients with AIS or transient ischemic attack (TIA), referred from a hospital in the acute stroke referral network or walk-ins, admitted to the stroke unit of Thammasat Hospital between October 2007 and January 2009 (16 months) were prospectively assessed. The main outcome measures were IV thrombolytic treatment rate, initial National Institutes of Health Stroke Scale (NIHSS) score, door-to-needle time, onset-to-treatment time (OTT), intracerebral hemorrhage, and morbidity and mortality at 3 months after onset. A total of 100 patients (59 from hospitals in the stroke referral network) received IV recombinant tissue plasminogen activator (rt-PA) therapy (21% of the admissions with AIS and TIA); 41% of the patients referred from a hospital in the network received IV rt-PA. The median NIHSS score before thrombolysis was 15 (range, 3-34). Mean door-to-needle time was 54 minutes (range, 15-125 minutes), and mean OTT was 160 minutes (range, 60-270 minutes). There were 13 asymptomatic intracerebral hemorrhages and 2 symptomatic intracerebral hemorrhages (1 fatal). By 3 months, 42 patients had achieved excellent recovery (modified Rankin Scale score of 0-1), and 14 had died. These outcomes are comparable to data from the National Institute of Neurological Disorders and Stroke and previous studies of IV rt-PA therapy in Thailand. Our findings indicate that integrating an acute stroke referral network into IV thrombolytic therapy for AIS in a community-based setting is safe and feasible and should help increase the rate of thrombolytic therapy. Previously inexperienced community-based centers can reproduce the experience and outcome measures reported by clinical trials and in the landmark literature of IV thrombolytic therapy in patients with stroke.

Pontine warning syndrome: case series and review of literature.

Crescendo transient ischemic attacks (TIAs) are defined as repeated frequent short-lasting episodes of focal neurologic deficit due to cerebral ischemia. The capsular warning syndrome, a subset of crescendo TIA, consists of repetitive episodes of motor dysfunction due to ischemia in the region of internal capsule. It is not clear that patients with ischemia in the pons can have a similar clinical presentation and course. We report 11 cases presenting with crescendo TIA in the form of pure motor hemiparesis or ataxic hemiparesis that later proved to have a paramedian pontine infarct. The presumed mechanism of these infarcts is penetrating basilar artery branch occlusion at their origin, also called basilar branch disease.

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.

Causes of Ischemic Stroke in Young Adults in Thailand: A Pilot Study

There is scarce information about ischemic stroke in young adults in Thailand. The purpose of this study was to explore the causes of ischemic stroke in Thai adults age 16-50 years. All ischemic strokes treated in persons in this age range between August 2006 and December 2008 were prospectively included. Stroke subtypes were classified according to Trial of ORG 10172 in Acute Stroke Treatment criteria as large-artery atherosclerosis (LAA), cardioembolism (CE), small-artery occlusion (SAO), stroke of other determined cause (OC), or stroke of undetermined cause (UND). The study group comprised 99 patients, with a mean age of 40 years and a mean National Institutes of Health Stroke Scale score of 8. In patients age <41 years, UND (32%; P = .0652) and OC (30%; P = .0167) were the most common stroke subtypes. In patients age 41-50 years, SAO (29%; P = .0947) and UND (21%) were the most common subtypes. Antiphospholipid syndrome (6%) and neurosyphilis (4%) were the leading causes of the OC subtype. Hyperlipidemia, smoking, and hypertension were common risk factors. Although the distribution of stroke subtypes was comparable with that found in previous studies from other countries, the identified causes were different.

Intravenous Thrombolysis in Thai Patients with Acute Ischemic Stroke: Role of Aging

BACKGROUND Intravenous thrombolysis is a standard treatment in eligible acute ischemic stroke (AIS) patients. However, the advisability of treating patients >80 years of age is still debated. The aim of this study was to evaluate the role of aging on the outcomes in Thai patients treated with intravenous thrombolysis. METHODS Patients with AIS treated with intravenous recombinant tissue-plasminogen activator (rtPA) between June 2007 and November 2010 were included. The demographics and measured outcome variables were compared between patients ≤70 and >70 years of age. Patients were also classified into 4 subgroups by the age ranges: ≤60 years, 61 to 70 years, 71 to 80 years, and ≥81 years of age. RESULTS Two hundred sixty-one patients were included. Seventeen patients (6.5%) were >80 years old. Higher mortality (20.2% vs 5.1%; P < .001) and symptomatic intracerebral hemorrhage (7.7% vs 1.2%; P = .004) were found in the patients >70 years of age when compared with younger patients, and the rate of favorable outcome was lower (38.1% vs 55.4%; P = .010). Higher mortality rates were seen with increasing age: 3%, 8%, 20%, and 21% in patients aged ≤60, 61 to 70, 71 to 80, and ≥81 years of age, respectively. CONCLUSIONS Thai stroke patients >70 years of age may carry a higher risk of mortality when treated with intravenous rtPA compared to patients ≤70 years of age.

Outcomes of Thai patients with acute ischemic stroke after intravenous thrombolysis

UNLABELLED The purpose of this study was to assess outcomes in Thai patients after treatment with intravenous recombinant tissue plasminogen activator (rtPA) and to determine the factors associated with good outcome and death. METHODS Patients with acute ischemic stroke who were treated with intravenous rtPA at Thammasat University Hospital between June 2007 and April 2010 were included. The measured outcome variables were good outcome (mRS 0,1) and death at 3 months. Stepwise multivariable analyses were performed by including the prespecified factors that were associated with the measured outcome variables in the univariate analysis. RESULTS The sample size was 197 patients. At 3 months, 93 patients (47%) had good outcomes while 23 patients (12%) died within the same period. Severe stroke (OR 0.19, 95% CI 0.08-0.44, p-value <0.0001) and history of hypertension (OR 0.39, 95% CI 0.16-0.93, p-value=0.033) were independently related to bad outcome at 3 months, while receiving intravenous nicardipine (OR 2.76, 95% CI 1.09-6.94, p-value=0.032) was associated with good outcome. Severe stroke (OR 5.89, 95% CI 1.29-26.85, p-value=0.022) and pretreatment high blood glucose levels (OR 8.06, 95% CI 1.21-53.62, p-value=0.031) each were independently associated with patient death. CONCLUSIONS Standard-dose intravenous rtPA in a cohort of Thai patients led to better clinical outcomes and comparable death rates when compared to other Asian cohorts receiving intravenous rtPA. Several factors were independently associated with patient outcomes at 3 months.

Intracerebral hemorrhage following intravenous thrombolysis in Thai patients with acute ischemic stroke

In Asia, there is limited information regarding symptomatic intracerebral hemorrhage (ICH) in patients treated with intravenous (iv) recombinant tissue plasminogen activator (rtPA). The aim of this study was to identify independent factors associated with symptomatic ICH following iv rtPA. The study included 192 patients with acute ischemic stroke who were treated with iv rtPA. Baseline characteristics were compared between patients with or without ICH. Symptomatic ICH occurred in 5.7% of patients and asymptomatic ICH in 13.0% of patients. An international normalized ratio (INR) ≥1.0 (odds ratio [OR]=4.89, p=0.036), atrial fibrillation (OR=7.21, p=0.009) and blood glucose concentration >8.325 mmol/L (OR=9.00, p=0.004), were independent risk factors for symptomatic ICH. Atrial fibrillation (OR=3.56, p=0.012) and severe stroke (National Institutes of Health Stroke Scale ≥15; OR=8.94, p<0.001) were independent risk factors for asymptomatic ICH. The prevalence of symptomatic ICH following iv rtPA in Thai patients was comparable to previous studies.

A novel ECGF1 mutation in a Thai patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive, multisystem disorder, which is clinically defined by ptosis, ophthalmoparesis, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and leukoencephalopathy. MNGIE is caused by mutations in the nuclear gene, endothelial cell growth factor 1 (ECGF1), encoding thymidine phosphorylase (TP). ECGF1 mutations cause severe loss of TP activity, abnormal accumulations of thymidine and deoxyuridine in plasma, and alterations of mitochondrial DNA. Here, we report the first Thai patient with MNGIE confirmed genetically by the identification of a homozygous novel ECGF1 gene mutation, c.100insC, which causes a frameshift and premature truncation of TP protein.