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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 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)
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)
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)