Brain : a journal of neurology
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Alzheimer's disease is characterized by the degeneration and loss of cholinergic neurones in the nucleus basalis Meynert, located within the substantia innominata at the ventral surface of the basal forebrain. An in vivo measure of morphological changes in the nucleus basalis Meynert would be of high relevance to better understand the structural correlate of cholinergic dysfunction in Alzheimer's disease. In this study, we applied a newly developed automated technique of image regression analysis, implemented through code written in Matlab 5.3 (MathWorks, Natick, MA), to the analysis of proton density weighted structural MRI of the basal forebrain from 13 patients with Alzheimer's disease (mean age = 77.5 years, SD = 4.4 years, 8 women) and 12 healthy elderly subjects (mean age = 62.3 years, SD = 5.6 years, 6 women). ⋯ The reduction of the signal intensity in an area corresponding to the anterior lateral nucleus basalis Meynert was significantly correlated with reduced grey matter concentration in the bilateral prefrontal cortex, inferior parietal lobule and cingulate gyrus. Our findings suggest that signal changes occur in patients with Alzheimer's disease in the substantia innominata which may be related to the loss or degeneration of cholinergic neurones and correspond to regional cortical grey matter atrophy. If replicated in an independent sample, our technique may be useful to detect degeneration of basal forebrain cholinergic neurones in vivo.
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Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. ⋯ There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination.
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The distribution and tempo of neuronal loss in Parkinson's disease correlates poorly with the characteristic and more widely spread intracellular changes associated with the disease process (Lewy bodies and Lewy neurites). To determine early intracellular changes in regions where cell loss is most marked (dopaminergic A9 substantia nigra) versus regions with Lewy bodies but where cell loss is limited, we assessed 13 patients with definite Parkinson's disease at various disease stages in comparison with controls. Using immunohistochemistry for alpha-synuclein, we confirmed the concentration of this protein in the soma of normal A9 neurons and in Lewy body pathology in brainstem catecholamine neurons in Parkinson's disease. ⋯ The selectivity of the changes observed in A9 nigral neurons suggests that these early intracellular changes predispose these neurons to more rapid cell loss in Parkinson's disease. The increased concentration of neuronal alpha-synuclein and pigment in normal A9 neurons may already predispose these neurons to precipitate alpha-synuclein around pigment-associated lipid under oxidative conditions. Overall, these changes may trigger a cascade of events leading to larger intracellular aggregates of alpha-synuclein and the dispersement of protective pigment to precipitate cell death in Parkinson's disease.
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Multicenter Study Clinical Trial
Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.
Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6-12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. ⋯ These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3-4 years in a large cohort of patients with severe Parkinson's disease.