Annals of neurology
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Annals of neurology · Aug 2009
Randomized Controlled Trial Multicenter StudyPhase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III.
Amyotrophic lateral sclerosis (ALS) is a devastating, and currently incurable, neuromuscular disease in which oxidative stress and mitochondrial impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice, and in clinical trials for neurodegenerative diseases other than ALS. Our aims were to choose between two high doses of CoQ10 for ALS, and to determine if it merits testing in a Phase III clinical trial. ⋯ CoQ10 at 2,700 mg daily for 9 months shows insufficient promise to warrant Phase III testing. Given this outcome, the adaptive Phase II design incorporating a dose selection and a futility test avoided the need for a much larger conventional Phase III trial.
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To investigate the association between the number of fast food restaurants and ischemic stroke in neighborhoods. ⋯ Controlling for demographic and SES factors, there was a significant association between fast food restaurants and stroke risk in neighborhoods in this community-based study.
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To identify design elements of clinical trials leading to US Food and Drug Administration approval of drugs for neurological diseases with and without orphan indications. ⋯ The US Food and Drug Administration has approved orphan drugs for neurological diseases without randomized, doubled-blind, placebo-controlled pivotal trials. As orphan drug development grows, demand will likely increase for alternative designs for conducting adequate and well-controlled studies to demonstrate drug efficacy.
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Annals of neurology · Aug 2009
Circulating endothelial microparticles as a marker of cerebrovascular disease.
Circulating endothelial microparticles (EMPs) have been reported to reflect vascular damage. Detailed profiling of these blood endothelial markers may adumbrate the pathogenesis of stroke or enable determination of the risk for stroke. We investigated EMP profiles in patients at risk for cerebrovascular disease. ⋯ Circulating EMP phenotypic profiles reflect distinct phenotypes of cerebrovascular disease and are markers of vascular pathology and an increased risk for ischemic stroke.
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Annals of neurology · Aug 2009
Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber syndrome.
The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are unknown. We explored the properties of neurons from human pediatric SWS cortex in vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites neurons in SWS cortex, as has been suggested for various types of epilepsies. ⋯ SWS cortical neurons have a relatively depolarized resting membrane potential and spontaneously fire action potentials that may contribute to increased network excitability. In contrast to previous data depicting excitatory and proconvulsive actions of GABA in certain pediatric and adult epilepsies, GABA plays mainly an inhibitory and anticonvulsive role in SWS pediatric cortex.