Long-Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients With Ischemic Stroke.

BACKGROUND: This study was performed to determine the clinical correlates and long-term prognostic implications of microbleed burden and location in Chinese patients with ischemic stroke. METHODS AND RESULTS: We recruited 1003 predominantly Chinese patients with ischemic stroke who received magnetic resonance imaging at the University of Hong Kong. We determined the clinical correlates of microbleeds and the long-term risks (3126 patient-years of follow-up) of recurrent ischemic stroke and intracerebral hemorrhage (ICH) by microbleed burden (0 versus 1, 2-4, and ≥5) and location, adjusting for age, sex, and vascular risk factors and stratified by antithrombotic use. Microbleeds were present in 450 of 1003 of the study population (119/450 had ≥5, 187/450 had mixed location). Having ≥5 microbleeds was independently associated with prior antiplatelet and anticoagulant use, whereas microbleeds of mixed location were independently associated with hypertension and prior anticoagulant use (all P<0.05). Microbleed burden was associated with an increased risk of ICH (microbleed burden versus no microbleeds: 1 microbleed: multivariate hazard ratio: 0.59 [95% confidence interval, 0.07-5.05]; 2-4 microbleeds: multivariate hazard ratio: 2.14 [95% confidence interval, 0.50-9.12]; ≥5 microbleeds: multivariate hazard ratio: 9.51 [95% confidence interval, 3.25-27.81]; Ptrend<0.0001), but the relationship of microbleed burden and risk of recurrent ischemic stroke was not significant (Ptrend=0.054). Similar findings were noted in the 862 of 1003 patients treated with antiplatelet agents only (ICH: Ptrend<0.0001; ischemic stroke Ptrend=0.096). Multivariate analysis revealed that, independent of vascular risk factors, antithrombotic use, and other neuroimaging markers of small vessel disease, having ≥5 microbleeds (multivariate hazard ratio: 6.08 [95% confidence interval, 1.11-33.21]; P=0.037) was identified as an independent predictor of subsequent ICH, but neither microbleed burden nor location was predictive of recurrent ischemic stroke risk. CONCLUSIONS: In Chinese patients with ischemic stroke, a high burden of cerebral microbleeds was significantly associated with an increased risk of ICH; however, neither microbleed location nor burden was associated with recurrent ischemic stroke risk.

Increased Risk of Stroke in Patients with Isolated Third, Fourth, or Sixth Cranial Nerve Palsies: A Nationwide Cohort Study.

BACKGROUND AND PURPOSE: The aim of this nationwide cohort study was to evaluate whether the occurrence of isolated 3rd, 4th or 6th cranial nerve (CN) palsies is associated with a higher risk of ischemic stroke. METHODS: This study utilized data from Taiwan Longitudinal Health Insurance Database during 1995-2012. Subjects aged 20 years or older who had isolated CN 3/4/6 palsies diagnosed by a neurologist or ophthalmologist between January 2000 and December 2011 were included. A set of propensity score matched, randomly sampled patients who had never been diagnosed with CN 3/4/6 palsies were extracted to constitute the control group (cases and controls = 1:4). All subjects were followed until death, loss due to follow-up or completion of the study. Cox proportional hazard regression model stratified by matched pairs was used to estimate the hazards ratio (HR) of ischemic stroke. RESULTS: A total of 657 patients with isolated CN 3/4/6 palsies (61.1% male, mean age 54.8 years) were identified. Compared with control group, the patients with isolated CN 3/4/6 palsies exhibited an increased risk of ischemic stroke (CN3: adjusted HR 3.69 (95% CI 2.20-6.19); CN4: 2.71 (95% CI 1.11-6.64); CN6: 2.15 (95% CI 1.31-3.52)). The association between CN 3/4/6 palsies and ischemic stroke was detected in both separate subgroup and sensitivity analyses. CONCLUSIONS: The patients with CN 3/4/6 palsies exhibited an increased risk of developing ischemic stroke. Therefore, isolated ocular motor nerves palsies appear to represent an unrecognized risk factor for ischemic stroke, and these require further confirmation and exploration.

Neuroprotective effect of honokiol and magnolol, compounds from Magnolia officinalis, on beta-amyloid-induced toxicity in PC12 cells.

Amyloid ß peptide (Aß) induced toxicity is a well-established pathway of neuronal cell death which might play a role in Alzheimer's disease. In this regard, the toxic effect of Aß on a cultured Aß-sensitive neuronal cell line was used as a primary screening tool for potential anti-Alzheimer's therapeutic agents. The effects of nine pure compounds (vitamin E, α-asarone, salidroside, baicolin, magnolol, gastrodin, bilobalide, honokiol and ß-asarone) from selected Chinese herbs on neuronal cell death induced by Aß in NGF-differentiated PC12 cells were examined. Only two of the studied compounds, honokiol and magnolol, significantly decreased Aß-induced cell death. Further experiments indicated that their neuroprotective effects are possibly mediated through reduced ROS production as well as suppression of intracellular calcium elevation and inhibition of caspase-3 activity. The results provide for the first time a scientific rationale for the clinical use of honokiol and magnolol in the treatment of Alzheimer's disease.