Nijasri C. Suwanwela

Magnetic resonance spectroscopy of the brain in neurologically asymptomatic HIV-infected patients

The CNS involvement is frequently found in human immunodeficiency virus (HIV) infection. The purpose of our study was to determine whether proton magnetic resonance spectroscopy (MRS) could detect early brain involvement in neurologically asymptomatic HIV-infected patients with normal MR imagings and to find the correlation between MRS and the immune status. We performed MRS in 30 HIV seropositive neurologically asymptomatic patients with normal MRI and compared the MRS findings with 13 controls. A statistically significant reduction in N-acetylaspartate (NAA)/creatine (Cr) and N-acetylaspartate (NAA)/choline (Cho) in both centrum semiovale (p < 0.005) and thalamic areas (p < 0.05) was found. There is no statistically significant difference as to choline (Cho)/creatine (Cr) and myoinositol (mI)/creatine (Cr) ratios in both regions. The difference of NAA/Cr was more pronounced in the white matter than in the gray matter. As for the immune status, there was a trend towards correlation between CD4 counts and NAA/Cr but devoid of statistical significance. Our results suggest that MRS is more sensitive than conventional MR imaging in detecting CNS involvement in neurologically asymptomatic HIV patients and may, therefore, be used for early detection of brain damage induced by HIV.

Efficacy and Safety of Combination Antiplatelet Therapies in Patients With Symptomatic Intracranial Atherosclerotic Stenosis

Background and Purpose— An optimal strategy for management of symptomatic intracranial atherosclerotic stenosis (ICAS) has not yet been established. We compared the efficacy of 2 combinations of antiplatelets, aspirin plus cilostazol (cilostazol group) verus aspirin plus clopidogrel (clopidogrel group), on the progression of ICAS, which is known to be associated with clinical stroke recurrence. Methods— In this investigator-initiated double-blind trial, 457 patients with acute symptomatic stenosis in the M1 segment of the middle cerebral artery or the basilar artery were randomly allocated into either a cilostazol group or a clopidogrel group. After 7 months of treatment, follow-up MR angiogram and MRI were performed. The primary end point was the progression of ICAS in comparison with stenosis on the baseline MR angiogram. Secondary end points included the occurrence of new ischemic lesions on MRI, composite of cardiovascular events, and major bleeding complications. Results— Cardiovascular events occurred in 15 of 232 patients (6.4%) in the cilostazol group and 10 of 225 (4.4%) in the clopidogrel group (P=0.312). Cilostazol did not reduce the progression of symptomatic ICAS (20 of 202) compared to clopidogrel (32 of 207) (odds ratio, 0.61; P=0.092), although favorable changes in serum lipoproteins were observed in the cilostazol group. There were no significant differences between the 2 groups with respect to new ischemic lesions (18.7% versus 12.0%; P=0.078) and major hemorrhagic complications (0.9% versus 2.6%; P=0.163). Conclusions— This trial failed to show significant difference in preventing progression of ICAS and new ischemic lesions between the 2 combination antiplatelet therapies in the patients with symptomatic ICAS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00130039.

Thrombolytic therapy in acute ischemic stroke in Asia: The first prospective evaluation

OBJECTIVE Intravenous thrombolytic therapy has been widely recommended as a standard treatment for acute ischemic stroke in most clinical practice guidelines. However, the experience in Asia is still limited. We report the first prospective case series of thrombolytic therapy in a developing Asian country. PATIENTS AND METHODS Consecutive patients with acute ischemic stroke who presented within 3 h of onset were screened under stroke fast track program. Those who were eligible were treated with intravenous recombinant tissue plasminogen activator (rt-PA). General and neurological examinations together with the National Institute of Health stroke scale (NHISS) and modified Rankin scale (MRS) were recorded prior to and after the treatment at 1 h, 24 h, on discharge and at 3 months. Hemorrhagic brain lesion and death within 3 months were also recorded. RESULTS Thirty-four patients or 2.1% of patients with acute stroke received intravenous thrombolysis. The mean pretreatment NIHSS was 18.8 and the majority of patients had stroke in the middle cerebral artery territory. The mean door-to-needle time was 72.6 min (ranged 20-150 min). Major neurological improvement, defined as improving of the NIHSS >8 points or NIHSS of 0 points at 24 h, was observed in 17 patients (50%). Intracerebral hemorrhage was detected in four cases (11.8%), two of them were symptomatic (5.9%) and one was fatal. CONCLUSION Intravenous thrombolysis can be given in patients with acute stroke in our population. Our cases were more severe than other studies. However, half of them experienced major neurological improvement. The risk of hemorrhagic brain lesion is not much higher than previously reported.

Risk Factors for Atherosclerosis of Cervicocerebral Arteries: Intracranial versus Extracranial

Objectives: To search for factors determining the site of atherosclerosis of the cervicocerebral arteries in patients from Bangkok (Thailand) with ischemic stroke in the carotid territory. Material and Methods: Patients with the clinical syndrome of stroke or transient ischemic attack in the carotid territory or with ocular stroke were retrospectively studied. They were divided into an intracranial and an extracranial carotid stenosis group based on their vascular imaging. The stroke risk factors were then compared. Results: There were 49 cases with extracranial carotid stenosis and 51 with intracranial stenosis. Among the patients with extracranial stenosis, 98% had associated intracranial disease, whereas none of those with intracranial stenosis had more than 50% of extracranial carotid stenosis. The presence of diabetes mellitus and a history of ischemic heart disease were found to be significantly more prevalent among patients with extracranial internal carotid artery stenosis. Conclusion: Diabetes mellitus as well as a history of ischemic heart disease were found to be more significantly prevalent in patients with combined extracranial internal carotid artery and intracranial stenosis. Extracranial carotid stenosis might represent a more severe atherosclerotic process of the cervicocerebral circulation when compared with intracranial stenosis.

Transcranial Doppler Ultrasound Criteria for Hemodynamically Significant Internal Carotid Artery Stenosis Based on Residual Lumen Diameter Calculated From En Bloc Endarterectomy Specimens

BACKGROUND AND PURPOSE Transcranial Doppler (TCD) is often used in conjunction with carotid duplex ultrasonography (CDUS) to evaluate the hemodynamic significance of internal carotid artery (ICA) stenosis. We examined the sensitivity and specificity of TCD criteria for detection of a hemodynamically significant stenosis (residual lumen diameter < 1.5 mm) at the origin of the ICA. METHODS We selected patients who underwent carotid end-arterectomy (CEA) and had preoperative TCD data available. Eighty-one patients underwent transorbital evaluation, 49 of whom also had transtemporal TCD performed. The endarterectomy specimens were removed en bloc and sectioned, and the minimal residual lumen diameter calculated by computer analysis. RESULTS For the transorbital approach, the strongest indicators of a residual lumen diameter < 1.5 mm were reversed flow in the ipsilateral ophthalmic artery and a > 50% peak systolic velocity difference between the carotid siphons (distal ICAs) in patients with unilateral ICA origin stenosis. They were 100% specific and 31% and 26% sensitive, respectively. For the transtemporal approach in patients with a unilateral stenosis, a > 35% difference in ipsilateral middle cerebral artery (MCA) peak systolic velocity relative to the contralateral MCA or a > 50% difference in contralateral anterior cerebral artery (ACA) peak systolic velocity relative to the ipsilateral ACA were 100% specific for identifying a residual lumen diameter of < 1.5 mm. Sensitivities were 32% and 43%, respectively. Irrespective of contralateral stenosis, a > 35% difference in ipsilateral MCA peak systolic velocity relative to the ipsilateral posterior cerebral artery had a 100% specificity and a 23% sensitivity for detecting a < 1.5 mm minimal residual lumen diameter. CONCLUSIONS Although the TCD sensitivity for detecting a hemodynamically significant stenosis is relatively low, it can be highly specific (up to 100%). We conclude that TCD enhances the specificity of highly sensitive CDUS criteria for detecting a hemodynamically significant ICA stenosis.

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.

Current status of intravenous thrombolysis for acute ischemic stroke in Asia

Background Data regarding thrombolysis for acute ischemic stroke in Asia are scarce and only a small percentage of patients are thrombolysed. The dose of intravenous tissue plasminogen activator (IV-tPA) in Asia remains controversial. Case-controlled observation studies in Asia included only Japanese patients and suggested the clinical efficacy and safety of low-dose IV-tPA (0·6 mg/kg body weight; max 60 mg) comparable to standard dose (0·9 mg/kg body weight; max. 90 mg). Reduced treatment cost, lower symptomatic intracerebral hemorrhage risk and comparable efficacy encouraged many Asian centers to adopt low-dose or even variable-dose IV-tPA regimens. We evaluated various Asian thrombolysis studies and compared with SITS-MOST registry and NINDS trial. Methods We included the published studies on acute ischemic stroke thrombolysis in Asia. Unadjusted relative risks and 95% Confidence intervals were calculated for each study. Pooled estimates from random effects models were used because the tests for heterogeneity were significant. Results We found only 18 publications regarding acute ischemic stroke thrombolysis in Asia that included total of 9300 patients. Owing to ethnic differences, stroke severity, small number of cases in individual reports, outcome measures and tPA dose regimes, it is difficult to compare these studies. Functional outcomes were almost similar (to Japanese studies) when lower-dose IV-tPA was used in non-Japanese populations across Asia. Interestingly, with standard dose IV-tPA, considerably better functional outcomes were observed, without increasing symptomatic intracerebral hemorrhage rates. Conclusions Variable dose regimens of IV-tPA are used across Asia without any reliable or established evidence. Establishing a uniform IV-tPA regimen is essential since the rapid improvements in health-care facilities and public awareness are expected to increase the rates of thrombolysis in Asia.

Comparison of Short (3-Day) Hospitalization followed by Home Care Treatment and Conventional (10-Day) Hospitalization for Acute Ischemic Stroke

This prospective randomized controlled study was designed to compare the treatment efficacy, safety and quality of life of ischemic stroke patients treated with conventional (10-day) hospitalization or short (3-day) hospitalization followed by home care treatment. One hundred and two patients with acute ischemic stroke who arrived within 48 h after symptom onset and met the inclusion criteria were studied. Patients were randomly assigned to either of two groups of treatment. Patients in the ‘hospitalization’ group were hospitalized for 10 days, whereas those in the ‘home care’ group were admitted only for the first 3 days and were followed at home under the home care program. The baseline characteristics were similar in the two groups. There was no difference in the number of deaths or dependency defined by the Modified Rankin scale more than or equal to 3 between the two groups at 6 months. The relative risk was 0.85 with a 95% confidence interval between 0.35 and 2.04. There was also no difference in the number of patients who had good outcome (NIHSS between 0 and 2 and Barthel index between 75 and 100) at 6 months. One patient in the home care group died due to massive intracerebral hemorrhage. Seventy-nine percent of patients in the home care group were satisfied with the home treatment program.

Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R

BACKGROUND Oxidation, inflammation, and apoptosis are three critical factors for the pathogenic mechanism of cerebral ischemia/reperfusion (I/R) injury. Curcumin exhibits substantial biological properties via anti-oxidation, anti-inflammation and anti-apoptotic effects; however, the molecular mechanism underlying the effects of curcumin against cerebral I/R injury remains unclear. OBJECTIVE To investigate the effects of curcumin on cerebral I/R injury associated with water content, infarction volume, and the expression of nuclear factor-kappa-B (NF-κB) and nuclear factor-erythroid-related factor-2 (Nrf2). METHODS Middle cerebral artery occlusion (MCAO, 1-hour occlusion and 24-hour reperfusion) was performed in male Wistar rats (n=64) as a cerebral I/R injury model. In the MCAO+CUR group, the rats were administered curcumin (300mg/kg BW, i.p.) at 30min after occlusion. The same surgical procedures were performed in SHAM rats without MCAO occlusion. At 24h post-operation, the parameters, including neurological deficit scores, blood brain barrier (BBB) disruption, water content, and infarction volume, were determined. Brain tissue NF-κB and Nrf2 expression levels were assayed through immunohistochemistry. RESULTS Compared with the SHAM group, BBB disruption, neurological deficit, and increased brain water content and infarction volume were markedly demonstrated in the MCAO group. NF-κB expression was enhanced in the MCAO group. However, in the MCAO+CUR group, the upregulation of Nrf2, an anti-oxidation related protein, was consistent with a significant decline in the water content, infarction volume, and NF-κB expression. CONCLUSION The protective effects of curcumin against cerebral I/R injury reflect anti-oxidation, anti-inflammation and anti-apoptotic activities, resulting in the elevation of Nrf2 and down-regulation of NF-κB.

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.