Kc Teo

Monoamine oxidase-B (MAO-B) inhibitors: implications for disease-modification in Parkinson’s disease

There is a substantial amount of evidence from experimental parkinsonian models to show the neuroprotective effects of monoamine oxidase-B (MAOB) inhibitors. They have been studied for their potential disease-modifying effects in Parkinson’s disease (PD) for over 20 years in various clinical trials. This review provides a summary of the clinical trials and discusses the implications of their results in the context of disease-modification in PD. Earlier clinical trials on selegiline were confounded by symptomatic effects of this drug. Later clinical trials on rasagiline using delayed-start design provide newer insights in disease-modification in PD but success in achieving the aims of this strategy remain elusive due to obstacles, some of which may be insurmountable.

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases – Relationships and comparisons with vascular markers of atherosclerosis

BACKGROUND Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. METHODS We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. RESULTS After a mean 81 ± 12 months follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P<0.01). BPV significantly correlated with all of the vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P<0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). CONCLUSIONS Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases.

Visit-to-visit systolic blood pressure variability predicts all-cause and cardiovascular mortality after lacunar infarct

Both blood pressure (BP) and its variability (BPV) are established risk factors for development of atherosclerotic disease and are associated with an increased risk for cardiovascular and all‐cause mortality. The prognostic implications of outpatient clinic visit‐to‐visit BPV amongst patients with lacunar infarction are nevertheless unknown.

Warfarin associated intracerebral hemorrhage in Hong Kong Chinese

Abstract Objectives: Warfarin-associated intracerebral hemorrhage (WICH) is a serious neurological condition associated with significant mortality and morbidity. We aimed to study the clinical features and factors that predict clinical outcome of Chinese patients with WICH. Methods: Medical records of patients with spontaneous intracerebral hemorrhage (ICH) admitted to our hospital between July 2001 and June 2010 were reviewed and those with WICH were studied in detail retrospectively. Results: Fifty-one patients with WICH were studied. The mean age was 74·3 ± 10·5 years and 52·9% of the patients were female. The mean international normalized ratio (INR) on presentation was 2·9 ± 1·0. The median ICH volume was 23·3 (10·4–59·3) ml. The mortality rate at 3–6 months for WICH was 62·0%. Multivariate logistic analysis revealed that an initial ICH volume of > 20 ml (OR 34·4, P  =  0·037) and presence of intraventricular hemorrhage (OR 22·9, P  =  0·046) were independently associated with poor outcome. Supratherapeutic INR (INR > 3·0) on admission (P  =  0·724) and complete correction of INR within 24 hours after admission (P  =  0·486) were not independent predictors of poor outcome. The median ICH volumes did not differ between INR groups (18·2 (9·4–61·1) ml for INR ≤ 3 vs 27·3 (13·7–58·5) ml for INR > 3, P  =  0·718). Neurological deterioration (ND) was documented in 19 (63·3%) of the 30 patients included in a smaller sub-cohort, and was associated with poor neurological outcome (OR 20·7, P  =  0·027). Warfarin was resumed in 7 of the 20 survivors. There were two episodes of recurrent WICH and one episode of ischemic stroke during a mean follow-up duration of 5·4 years. In survivors who were not resumed on warfarin, there were two episodes of recurrent ICH and 12 episodes of ischemic vascular events (nine ischemic strokes) during a mean follow-up duration of 2·6 years. Conclusion: Warfarin-associated intracerebral hemorrhage is a very serious complication of warfarin therapy with high mortality and morbidity. Initial ICH volume, presence of intraventricular hemorrhage, and ND are independent predictors of clinical outcome.

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]; P trend<0.0001), but the relationship of microbleed burden and risk of recurrent ischemic stroke was not significant (P trend=0.054). Similar findings were noted in the 862 of 1003 patients treated with antiplatelet agents only (ICH: P trend<0.0001; ischemic stroke P trend=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.