Prognostic factors and treatment effect in the CHIMES study.

BACKGROUND: Stroke trials often analyze patients with heterogeneous prognoses using a single definition of outcome, which may not be applicable to all subgroups. We aimed to evaluate the treatment effects of MCL601 among patients stratified by prognosis in the Chinese Medicine Neuroaid Efficacy on Stroke Recovery (CHIMES) study. METHODS: Analyses were performed using data from the CHIMES study, an international, randomized, placebo-controlled, double-blind trial comparing MLC601 with placebo in patients with ischemic stroke of intermediate severity in the preceding 72 hours. All subjects with baseline data and the modified Rankin Scale (mRS) score at 3 months were included. RESULTS: Data from 1006 subjects were analyzed. The predictive variables for mRS score greater than 1 at month 3 were age older than 60 years (P < .001), baseline National Institutes of Health Stroke Scale score 10-14 (P < .001), stroke onset to initiation of study treatment of more than 48 hours (P < .001), and female sex (P = .026). A higher number of predictors was associated with poorer mRS score at month 3 for both placebo (P < .001) and treatment (P < .001) groups. The odds ratio (OR) for achieving a good outcome increased with the number of predictors and reached statistical significance in favor of MLC601 among patients with 2 to 4 predictors combined (unadjusted OR = 1.44, 95% confidence interval, 1.02-2.03; adjusted OR = 1.60, 95% confidence interval, 1.10-2.34). CONCLUSIONS: Age, sex, baseline National Institutes of Health Stroke Scale score, and time to first dose are predictors of functional outcome in the CHIMES study. Stratification by prognosis showed that patients with 2 or more predictors of poorer outcome have better treatment effect with MLC601 than patients with single or no prognostic factor. These results have implications on designing future stroke trials.

Intravenous Heroin-Associated Delayed Spongiform Leukoencephalopathy: Case Report and Reviews of the Literature.

Heroin-associated spongiform leukoencephalopathy is a rare, and sometimes fatal, condition usually caused by vapor inhalation of heroin. The authors report a 41-year-old man who was diagnosed with delayed spongiform leukoencephalopathy three weeks after injecting heroin intravenously. He had been admitted to another hospital due to acute heroin overdose, which had occurred four hours after intravenous injection of an unknown amount of heroin. His clinical condition showed progressive improvement and he was discharged 12 days after admission. Three weeks after this episode, his cognitive functioning declined. Akinetic mutism, spasticity and hyperreflexia of all extremities were observed. Electroencephalography (EEG) and imaging of the brain showed typical characteristics of spongiform leukoencephalopathy. The three and six-month follow-up of the patient showed clinical improvement and this was corroborated through EEG measures and brain imaging. The discussion summarizes eight previously reported cases of intravenous heroin associated spongiform leukoencephalopathy and compares them to the authors'case.

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.

Prophylactic botulinum type A toxin complex (Dysport®) for migraine without aura.

OBJECTIVE: To evaluate the efficacy, safety, and optimum dose of a highly purified Clostridium botulinum type A toxin-hemagglutinin complex (Dysport) for migraine prophylaxis. BACKGROUND: Botulinum toxin type-A has demonstrated good efficacy in several open-label studies of patients with migraine, involving either individualized or standardized protocols, although data from placebo-controlled trials have been conflicting. METHODS: A 12-week, double-blind, randomized trial of Dysport (120 or 240 units) vs placebo was conducted in 6 centers in Thailand to evaluate the efficacy, safety, and optimum dose of botulinum toxin type-A (Dysport) for migraine prophylaxis. A total of 128 patients with migraine without aura were enrolled. The primary end point was the change in the mean number of migraine attacks per 4-week period from the pre-treatment period to 8-12 weeks post injection. Secondary efficacy measures included the change in the mean total intensity score from the pre-treatment period to 8-12 weeks, the investigator and patient global assessments of change at each visit compared with pre-treatment, and Migraine Disability Assessment and Short Form-36 scores. RESULTS: Change in number of migraine attacks from pre-treatment to weeks 8-12 was not significantly different. There was a greater improvement in total intensity score at weeks 8-12 with Dysport-240 (not significant), and interim visit data showed that this was significant at weeks 0-4 (P = .03 Dysport-240 vs placebo). The mean duration of headache during weeks 0-4 was lower with Dysport-240 (P = .04 vs placebo). Improvements in patient and investigator global assessments of change between weeks 0-4 and 8-12 were significant for the Dysport-240 group (both P < .05 vs placebo). CONCLUSIONS: Limitations in study design and assessment tools employed may have contributed to the inconclusive nature of the primary end point data. Dysport-240 showed significant benefit over placebo at some end points and further trials with more appropriate outcome measures are required to evaluate effectively this treatment.

Correlation between bispectral index value and modified Glasgow Coma Scale score in dogs with altered level of consciousness.

OBJECTIVE: This study aims to identify the correlation between bispectral index (BIS) value and modified Glasgow Coma Scale (MGCS) score in dogs with altered level of consciousness (ALOC). DESIGN: This prospective, observational, clinical study was conducted from February 2016 to March 2017, and follow-up was conducted until the death of dogs or their discharge from the hospital. SETTING: This study was performed at the Small Animal Teaching Hospital. ANIMALS: A total of 31 client-owned dogs (males, 20; females, 11) with ALOC and MGCS score <18 with no restrictions for age, breed, sex, and body weight were included. Dogs that received neuromuscular blocking agents before MGCS score evaluation were excluded. INTERVENTIONS: BIS values were measured using the Covidien BIS Loc 2 Channel OEM module and a pediatric 4 sensor with a bifrontal application pattern. MEASUREMENTS AND MAIN RESULTS: Minimal databases of initial neurological assessment, blood profiles, and chest and skull radiographs were developed. In addition, MGCS scores and BIS values were recorded. The mean BIS values for mild, moderate, and severe brain injuries were 89.14 ± 6.52, 77.21 ± 9.82, and 50.58 ± 27.04, respectively. Correlation analysis revealed a significantly positive relationship between BIS values and MGCS scores (r = 0.75; P < 0.001). CONCLUSIONS: The significant correlation observed between MGCS scores and BIS values in dogs with ALOC demonstrated the usefulness of BIS as an alternative to MGCS for monitoring consciousness in patients with ALOC caused by traumatic brain injury, encephalitis, etc.

Safety and tolerability of galantamine in possible Alzheimer's disease with or without cerebrovascular disease and vascular dementia in Thai patients.

The purpose of this study was to explore factors that influence the clinical safety and tolerability associated with galantamine administration in Thai Alzheimer's disease patients with or without cerebrovascular disease and vascular dementia. This was an analysis of previous study. Tolerability and safety profile were analyzed according to sex, age, body weight, Thai mental state examination (TMSE) score, Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) score, and Alzheimer's disease cooperative study/activities of daily living (ADCS/ADL) score. The most common adverse events were nausea, dizziness, and weight loss which more often occurred during the dose-escalation phase. Mean body weight lost at week 24 was 0.9 kg. Sex, age, body weight, and ADAS-cog score did not influence the incidence of any adverse events. Dizziness was more likely to occur in patients with low TMSE and high ADCS/ADL score (p = 0.02 and p = 0.050, respectively). Patients with TMSE score equal or higher than 23 more often experienced muscle cramps and fatigue than who had TMSE lower 23 (p < 0.05). However, flexible dose escalation of galantamine with a 4-week schedule was safe and well tolerated in Thai AD patients.

Thai venous stroke prognostic score: TV-SPSS.

BACKGROUND AND OBJECTIVE: Prognosis of cerebral venous sinus thrombosis (CVST) has never been studied in Thailand. A simple prognostic score to predict poor prognosis of CVST has also never been reported. The authors are aiming to establish a simple and reliable prognostic score for this condition. MATERIAL AND METHOD: The medical records of CVST patients from eight neurological training centers in Thailand who received between April 1993 and September 2005 were reviewed as part of this retrospective study. Clinical features included headache, seizure, stroke risk factors, Glasgow coma scale (GCS), blood pressure on arrival, papilledema, hemiparesis, meningeal irritation sign, location of occluded venous sinuses, hemorrhagic infarction, cerebrospinal fluid opening pressure, treatment options, length of stay, and other complications were analyzed to determine the outcome using modified Rankin scale (mRS). Poor prognosis (defined as mRS of 3-6) was determined on the discharge date. RESULTS: One hundred ninety four patients' records, 127 females (65.5%) and mean age of 36.6 +/- 14.4 years, were analyzed Fifty-one patients (26.3%) were in the poor outcome group (mRS 3-6). Overall mortality was 8.4%. Univariate analysis and then multivariate analysis using SPSS version 11.5 revealed only four statistically significant predictors influencing outcome of CVST They were underlying malignancy, low GCS, presence of hemorrhagic infarction (for poor outcome), and involvement of lateral sinus (for good outcome). Thai venous stroke prognostic score (TV-SPSS) was derived from these four factors using a multiple logistic model. CONCLUSION: A simple and pragmatic prognostic score for CVST outcome has been developed with high sensitivity (93%), yet low specificity (33%). The next study should focus on the validation of this score in other prospective populations.

Migraine disability awareness campaign in Asia: migraine assessment for prophylaxis.

OBJECTIVES: This study aimed to survey the headache diagnoses and consequences among outpatients attending neurological services in 8 Asian countries. METHODS: This survey recruited patients who consulted neurologists for the first time with the chief complaint of headache. Patients suffering from headaches for 15 or more days per month were excluded. Patients answered a self-administered questionnaire, and their physicians independently completed a separate questionnaire. In this study, the migraine diagnosis given by the neurologists was used for analysis. The headache symptoms collected in the physician questionnaire were based on the diagnostic criteria of migraine proposed by the International Classification of Headache Disorders, second edition (ICHD-2). RESULTS: A total of 2782 patients (72% females; mean age 38.1 15.1 years) finished the study.Of them, 66.6% of patients were diagnosed by the neurologists to have migraine, ranging from 50.9% to 85.8% across different countries.Taken as a group, 41.4% of those patients diagnosed with migraine had not been previously diagnosed to have migraine prior to this consultation. On average, patients with migraine had 4.9 severe headaches per month with 65% of patients missing school,work, or household chores. Most (87.5%) patients with migraine took medications for acute treatment. Thirty-six percent of the patients had at least one emergency room consultation within one year. Only 29.2% were on prophylactic medications. Neurologists recommended pharmacological prophylaxis in 68.2% of patients not on preventive treatment. In comparison, migraine prevalence was the highest with ICHD-2 "any migraine" (ie, migraine with or without migraine and probable migraine) (73.3%) followed by neurologist-diagnosed migraine (66.6%) and ICHD-2 "strict migraine" (ie, migraine with or without aura only) (51.3%). About 88.6% patients with neurologist-diagnosed migraine fulfilled ICHD-2 any migraine but only 67.1% fulfilled the criteria of ICHD-2 strict migraine. CONCLUSIONS: Migraine is the most common headache diagnosis in neurological services in Asia. The prevalence of migraine was higher in countries with higher referral rates of patients to neurological services. Migraine remains underdiagnosed and under-treated in this region even though a high disability was found in patients with migraine. Probable migraine was adopted into the migraine diagnostic spectrum by neurologists in this study.

The effect of Galantamine on sleep quality in Thai Alzheimer's disease patients.

OBJECTIVE: To study the effect of Galantamine on sleep quality in Thai Alzheimer's disease (AD) patients with or without cerebrovascular disease. MATERIAL AND METHOD: A 6 month, multicenter open-label, uncontrolled trial was undertaken in 75 mild to moderate Alzheimer's disease patients with or without cerebrovascular disease. Eligible patients received a flexible-dose of Galantamine 16 or 24 mg/day for 24 weeks. The Pittsburgh Sleep Quality Index (PSQI) with self-analysis questionnaires were used to evaluate sleep quality. Analyses were based on the intent-to-treat population. RESULTS: Seventy-five eligible patients with mild to moderate Alzheimer's disease with or without cerebrovascular disease (male:female = 32:43, age range 74.5 +/- 0.9) were included and 58 patients (79%) completed the present study. The global PSQI scores showed some improvement over baseline (week 0 = 5.10 +/- 3.08, week 4 = 4.37 +/- 2.48, week 8 = 4.65 +/- 2.71, week 24 = 3.70 +/- 2.12) but were not yet statistical significant. In contrast, most of each component scores such as sleep quality, sleep latency, sleep duration, sleep disturbances, sleep medication, and daytime dysfunction except sleep efficiency, showed significant differences from baseline after week 8. Moreover, there were no significant differences in global PSQI and component scores between mild and moderate stages of Thai AD patients or between men and women patients. CONCLUSION: The result of the present study may be consistent with Galantamine being safe and can maintain good sleep quality for mild to moderate Thai AD patients with or without VaD. Galantamine doses of 16-24 mg/day were well tolerated.

Health utilities of patients with multiple sclerosis and neuromyelitis optica spectrum disorders in Thailand.

BACKGROUND: Multiple sclerosis (MS) and neuromyelitis optica spectrum (NMOSD) cause several symptoms that negatively impact on patient's quality of life. No study has ever conducted to examine the quality of life of MS and NMOSD patients, especially in terms of health utility, among the non-western population. This study aims to examine health utility among MS and NMOSD patients in Thailand. METHODS: A multicenter cross-sectional study including 104 MS and 186 NMOSD patients was conducted. Health utility was measured using EQ-5D questionnaire. Demographic data, clinical data and Expanded Disability Status Scales (EDSS) were also collected. RESULTS: Health utility scores of MS or NMOSD were 0.41 ±â€¯0.36 and 0.41 ±â€¯0.32, respectively. No significant difference between MS and NMOSD in term of health utility score was found. Pain, mobility, and anxiety/depression are the three most affected domains among both MS and NMOSD patients. Age at onset less than 40 years and EDSS score less than or equal to 2.5 were significantly associated with higher health utility score in MS and NMOSD patients. CONCLUSION: Our findings clearly demonstrated the negative impact of MS and NMOSD on patients' health-related quality of life. Effective interventions that target pain, mobility, and anxiety/depression should be provided to improve quality of life of these patients. Health utility estimates from this study can be used as an important input for economic evaluations of treatments for MS and NMOSD to inform resource-allocation decisions.

Effect of doses on the bioavailability of phenytoin from a prompt-release and an extended-release preparation: single dose study.

OBJECTIVE: To determine the effect of doses on the bioavailability of a prompt-release and an extended-release phenytoin capsule after given as single doses. MATERIAL AND METHOD: Eight healthy male volunteers were given single oral doses of 100, 200, and 300 mg of a prompt-release preparation (Ditoin) and an extended-release phenytoin (Dilantin Kapseals) preparation in a crossover design with a two weeks washout period after an overnight fast. Serial blood samples were collected over 72 h post-dose. Plasma phenytoin concentrations were determined by HPLC and pharmacokinetic parameters were analyzed by non-compartmental model. RESULTS: Rate of phenytoin absorption from the prompt-release preparation was more prolonged after the 300mg dose (T(max) 4.5 h) than those of the 100- and 200-mg doses (T(max) 3.5 and 3 h, respectively). Similarly, the T(max) of the 200- and the 300-mg extended-release preparation (5.5 and 4 h) were more prolonged than the 100-mg dose (3 h). Bioequivalence analysis showed that the C(max) of all doses of the prompt-release preparation were higher than those values of the extended-release preparation with the mean C(max) ratio (90% CI) of 1.32 (1.24-1.40), 1.26 (1.14-1.40), and 1.29 (1.10-1.51) for the 100-, 200- and 300-mg doses, respectively. The extent of absorption (AUC(0-infinity)) of 100-mg phenytoin was bioequivalent between the two preparations [mean AUC ratio (90% CI) of 1.15 (1.11-1.18)], however, for higher doses, the prompt-release products produced higher bioavailability than the extended-release products [mean AUC ratio (90% CI) of 1.19 (1.07-1.33) and 1.17 (0.98-1.38), respectively for the 200- and 300-mg doses]. The difference in the bioavailability did not affect the elimination of phenytoin and their half-lives were comparable (11-13 h). CONCLUSION: The bioavailability of phenytoin from both preparations increased proportionally over the dose range of 100-300-mg, however, the bioavailability of the prompt-release preparation was higher than the corresponding doses of the extended-release product.

Efficacy and safety of piribedil in early combination with L-dopa in the treatment of Parkinson's disease: a 6-month open study.

BACKGROUND: Piribedil is a non-ergot D2/D3 dopamine agonist with antagonistic effect on alpha2-adrenoceptors and lack of agonist properties at 5-HT2A/2C receptors. Previous studies indicated its efficacy in monotherapy as well as in combinatio' s disease in L-dopa-treated parkinsonian patients. PATIENTS AND METHOD: A 6-month, open-labeled, multicenter study was conducted in Thai Parkinsonian patients who were insufficiently controlled by L-dopa (< or = 600 mg/day). Piribedil 50 mg in retard form was titrated upward to 150 mg/day (50 mg tid) by the 5th week and up to 6 months as an add-on treatment. L-dopa daily dose was kept stable until the 3rd month and could be adjusted afterwards. The main efficacy parameter was the change in UPDRS part III score versus baseline over Full Analysis Set, score variation, and percentage of responders defined by at least 30% decrease from baseline of total UPDRS part III score. The secondary efficacy criteria were changes in L-dopa dose between the third month and the end of the study, UPDRS part II score variation, Hoehn and Yahr stage variation and Schwab and England Activities of Daily Living Scale variation. The acceptability of piribedil was assessed by physical examination, weight, blood pressure and heart rate as well as the reported adverse events. RESULTS: Twenty-nine patients (55.2% male) with the mean age of 64.0 +/- 7.2 years and mean duration of disease of 18.3 +/- 8.2 months were recruited The mean UPDRS part III score at baseline was 19.8 +/- 11.4. After 6-month treatment with piribedil, mean UPDRS part III score significantly decreased to 6.6 +/- 4.7 (p < 0.0001) with mean score variation of 13.3 +/- 10.3. Twenty-seven patients (93.1%) were responders. Mean UPDRS part II score was significantly decreased from 7.2 +/- 5.4 at baseline to 2.7 +/- 2.1 at the end of 6 months (p < 0.0001). Hoehn and Yahr stage and Schwab and England Activities of Daily Living Scale were also significantly improved Reported adverse events were mainly gastrointestinal symptoms. Blood pressure and heart rate were not significantly changed during the study period. Peak dose dyskinesia was reported only in one patient. Two patients (6.9%) were withdrawn because of adverse events. CONCLUSION: Piribedil was effective on motor symptoms during a 6-month treatment in early parkinsonian patients insufficiently controlled by L-dopa and it was well tolerated.

Management of cholesterol to reduce the burden of stroke in Asia: consensus statement.

Stroke is a major cause of morbidity and mortality in Asia, and its pattern is changing. The incidence of haemorrhagic stroke is declining while the incidence of ischaemic stroke caused by large artery atherothromboembolism is increasing secondary to an increase in the prevalence of hypercholesterolaemia. The Working Group on Stroke and Lipids Management in Asia Consensus Panel assembled leading experts from the region to reach a consensus on how to address this challenge. The group discussed the observational epidemiology of the relationship between cholesterol and risk of stroke, the clinical trial evidence base for cholesterol-lowering for stroke prevention, and issues specific to stroke and lipid management for Asian doctors and patients. Stroke guidelines from many of the Asian countries have recently recommended consideration of statins for recurrent stroke prevention in patients with previous ischaemic stroke or transient ischaemic attack. However, because these recommendations have yet to be implemented widely, there is a need to educate Asian physicians and patients about the importance of adequate control of hypercholesterolaemia. Further trials of statins in Asian patients are also needed, particularly in those with intracranial stenosis.