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We report a natural history study of 216 patients with primary progressive (PP)- multiple sclerosis defined by at least 1 year of exacerbation-free progression at onset. This represents 19.8% of a largely population-based patient cohort having a mean longitudinal follow-up of 23 years. This subgroup of PP-multiple sclerosis patients had a mean age of onset(More)
The purpose of this study was to examine whether mental fatigue influences the perceived effort required to complete fairly light and hard effort self-paced exercise challenges. 12 participants completed 2 trials in a randomised cross-over design. Each participant was required to complete a time-matched pre-exercise task: 1) a continuous cognitive activity(More)
The chronological accumulation of mitochondrial dysfunction has been proposed as a potential mechanism in the physiological processes of aging. Cytochrome c oxidase deficient, succinate dehydrogenase positive muscle fibers containing high copy numbers of a mitochondrial DNA mutation are a pathological hallmark of mitochondrial DNA disorders. We show that(More)
OBJECTIVE To determine whether hippocampal neurons and choroidal epithelial cells demonstrate a mitochondrial enzyme deficiency in AD more frequently than in normal aging. BACKGROUND High levels of mutant mitochondrial DNA (mtDNA) cause a deficiency in cytochrome c oxidase (COX) (complex IV activity) because three of its 13 subunits are encoded for by(More)
Defects of mitochondrial function have been proposed as a potential mechanism in the development and pathogenesis of Alzheimer's disease (AD) and neuronal apoptosis. Mitochondrial enzyme-deficient pyramidal neurones are found in greater quantities in the hippocampus of AD patients than in age-matched controls. The presence of these neurones indicates that(More)
Mitochondrial abnormalities, in particular the accumulation of mitochondrial DNA mutations, have been proposed as a potential cause of normal ageing. One group of patients with mtDNA disorders have a nuclear DNA defect which accelerates the chronological accumulation of mitochondrial DNA mutations. These patients provide an ideal means of investigating(More)
BACKGROUND The promising utility of multi-modality evoked potential batteries to objectively measure multi-tract dysfunction has been evaluated by several groups using different methods. OBJECTIVE To independently evaluate the use of multi-modality evoked potential batteries as surrogate biomarkers for both physical and cognitive status in a cohort of(More)
The natural history of primary progressive multiple sclerosis (PP-multiple sclerosis) recently has been defined in a geographically based multiple sclerosis population. For a series of prognostically defined hypothetical entry criteria based upon current trends in presentation to the London Multiple Sclerosis Clinic, we determined the number of patients who(More)
The identification of cytochrome c oxidase (COX)-deficient/succinate dehydrogenase (SDH)- positive cells using sequential histochemistry has proved important in the identification of cells with high mitochondrial DNA (mtDNA) mutant load. We demonstrate large numbers of COX-deficient/SDH-positive neurons in a mosaic pattern throughout the CNS of a patient(More)
This paper describes the use of a hierarchical design representation standard, CHDStd, as part of the architecture of the Chip Hierarchical Design System (CHDS). Details are given on CHDStd-based hierarchy mechanisms and processes required to support Forward Timing-Driven Hierarchical Design capabilities needed for chip design using 0.25u-0.18u technologies(More)