Hyperglycemia-related FAS gene and hsa-let-7b-5p as markers of poor outcomes for ischaemic stroke.

BACKGROUND AND PURPOSE: Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia-associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia-induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA-messenger RNA (mRNA) biomarkers in addition to using traditional risk factors. METHODS: After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression. RESULTS: The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa-let-7b-5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system. CONCLUSIONS: Combined analyses of Fas and has-let-7b-5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia-induced stroke outcomes.

Efficacy of phenytoin, valproic acid, carbamazepine and new antiepileptic drugs on control of late-onset post-stroke epilepsy in Taiwan.

BACKGROUND AND PURPOSE: To assess the efficacy of various antiepileptic drugs (AEDs) for controlling post-stroke epilepsy. METHODS: This nationwide cohort study was conducted by using data from 2004 to 2008 on new occurrence of post-stroke epilepsy obtained from the National Health Insurance Research Database of Taiwan. The examined AEDs were phenytoin (PHT), valproic acid (VPA), carbamazepine (CBZ) and new AEDs. Recurrent seizures requiring either emergency room (ER) visits or hospitalization were used to measure the efficacy of seizure control. The Kaplan-Meier failure curve and Cox proportional hazard regression analyses were used to compare the risk of seizure recurrence in patients taking various AEDs. RESULTS: In all, 3622 late-onset post-stroke epilepsy patients were selected. Overall, 1.05 and 0.70 recurrent seizure incidences occurred per 100 person-months based on ER visits [95% confidence interval (CI) 0.95-1.15] and hospitalizations (95% CI 0.62-0.78), respectively. The incidences of ER visits for patients using different AEDs were 1.26, 0.70, 0.43 and 0.38 per 100 person-months for PHT, VPA, CBZ and new AEDs, respectively. Compared with patients using PHT, the adjusted hazard ratios for ER visits were 0.56 (95% CI 0.42-0.74; P < 0.001), 0.37 (95% CI 0.18-0.75; P = 0.006) and 0.28 (95% CI 0.15-0.52; P < 0.001) for patients using VPA, CBZ and new AEDs, respectively. The adjusted hazard ratios of hospitalizations for seizure recurrence yielded similar results. CONCLUSIONS: This large nationwide, population-based study demonstrated that late-onset post-stroke epilepsy patients using VPA and new AEDs have better seizure control than those using PHT as demonstrated by lower risks of ER visits and hospitalization.

Central nervous system infections and stroke -- a population-based analysis.

BACKGROUND: Chronic central nervous system (CNS) infections have been found to associate with cerebrovascular complications. Acute CNS infections are more common than chronic CNS infections, but whether they could increase the risk of vascular diseases has not been studied. METHODS: The study cohort comprised all adult patients with diagnoses of CNS infections from Taiwan National Health Insurance Research Database during 2000-2009 (n = 533). The comparison group were matched by age, sex, urbanization, diagnostic year, and vascular risk factors of cases (cases and controls = 1:5). Patients were tracked for at least 1 year. Kaplan-Meier analysis was used to compare the risk of stroke and acute myocardial infarction (AMI) after adjusting censoring subjects. RESULTS: After adjusting the patients demographic characteristics and comorbidities, the risk of patients with CNS infections developing stroke was 2.75-3.44 times greater than their comparison group. More than 70% of the stroke events were occurring within 1 year after CNS infections. The risk of AMI was not found as we compared patients with and without CNS infections. CONCLUSIONS: The population-based cohort study suggested that adult patients with CNS infections have higher risk to develop stroke but not AMI, and the risk is marked within a year after infections.

Effects of the apolipoprotein E ε4 allele on functional MRI during n-back working memory tasks in healthy middle-aged adults.

BACKGROUND AND PURPOSE: APOE4 is the best-documented genetic risk factor for sporadic AD. Previous research showed that APOE4 is associated with increased risk of occurrence and earlier onset of AD in a gene dose-dependent manner. However, the specific role of APOE4 in processing of brain functions requires further investigation. Investigators have used fMRI to measure brain activity on the basis of the blood oxygen level-dependent contrast. This study investigates the effects of APOE4 on fMRI during n-back WM tasks in healthy middle-aged adults. MATERIALS AND METHODS: From 110 participants, 81 individuals without objective or subjective cognitive impairment underwent APOE genotyping. Nine APOE4 carriers and 9 age- and sex-matched non-APOE4 controls were recruited for fMRI examinations during WM tasks. RESULTS: Both groups displayed increased brain activation in response to increases in WM loads. During low-WM-load tasks, the APOE4 carriers recruited significantly greater additional processing resources than the non-APOE4 carriers. During moderate- and high-WM-load tasks, the APOE4 carrier group displayed fewer increases in activation than the non-APOE4 carrier group. CONCLUSIONS: APOE genetic polymorphisms may affect brain functioning in subjects without dementia. The patterns of brain activation during different levels of WM load suggest possible subclinical impairment of WM capacity in APOE4 carriers (ClinicalTrials.gov registration: NCT01287819).