Articles: amyotrophic-lateral-sclerosis-pathology.
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To evaluate basal ganglia changes along the amyotrophic lateral sclerosis (ALS)-ALS-frontotemporal dementia (FTD) continuum using multiple, complementary imaging techniques. ⋯ We demonstrate correlations between basal ganglia measures and structure-specific neuropsychological performance and a gradient of incremental basal ganglia pathology across the ALS-ALS-FTD spectrum, suggesting that the degree of subcortical gray matter pathology in C9orf72-negative ALS is closely associated with neuropsychological changes.
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J. Neurol. Neurosurg. Psychiatr. · Sep 2015
Comparing brain structural MRI and metabolic FDG-PET changes in patients with ALS-FTD: 'the chicken or the egg?' question.
Our previous voxel based morphometry (VBM) studies in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (ALS-FTD) showed reduced motor and extramotor grey matter (GM) volume when compared to neurological controls. However, erroneously high GM values can result because VBM analysis includes both cortical gyri and sulci as a single GM region. In addition, the relationship between structural and functional changes is unknown. Therefore, we determined whether GM volumetric changes seen in patients with ALS-FTD were due to changes in cortical thickness, area or both, and compared these structural changes with metabolic changes as revealed by positron emission tomography (PET). ⋯ Metabolic changes corresponded well with structural changes in motor and extramotor areas, and sometimes occurred even in the absence of GM volume reduction. Coincident structural and functional GM changes suggest that neurodegeneration may occur as "neuronopathy" in patients with ALS-FTD.
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Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease leading to progressive and lethal paralysis. The disease process is multi-factorial and is characterized by selective motor neuron degeneration. Previous work demonstrated that the local concentration of various growth factors can influence motor neuron survival and disease progression. ⋯ By means of grip strength and nerve conductance analysis we show that kit(w-sh/w-sh) mice have diminished strength and slightly impaired compound muscle action potential latency, although the number of neurons is similar across genotypes. Decreasing kit gene expression in SOD1(G93A) mice is detrimental and our results imply that this effect is independent of mast cells, as tested by ketotifen administration. To conclude, our data expand on the protective role of growth factors in ALS, as decreasing c-kit by approximately 70% is detrimental in SOD1(G93A) mice.
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In this study, we analyzed the spatiotemporal alterations of phospholipid composition in the spinal cord of an amyotrophic lateral sclerosis (ALS) mouse model (G93A-mutated human superoxide dismutase 1 transgenic mice [SOD1(G93A) mice]) using imaging mass spectrometry (IMS), a powerful method to visualize spatial distributions of various types of molecules in situ. Using this technique, we deciphered the phospholipid distribution in the pre-symptomatic stage, early stage after disease onset, and terminal stages of disease in female SOD1(G93A) mouse spinal cords. These experiments revealed a significant decrease in levels of docosahexaenoic acid (DHA)-containing phosphatidylcholines (PCs), such as PC (diacyl-16:0/22:6), PC (diacyl-18:0/22:6), and PC (diacyl-18:1/22:6) in the L5 anterior horns of terminal stage (22-week-old) SOD1(G93A) mice. ⋯ Thus, our study showed a significant decrease in DHA-containing PCs, but not other PCs, in the terminal stage of ALS in model mice, which is likely to be a reflection of neuronal loss in the anterior horns of the spinal cords. Given its enrichment in dorsal sensory regions, the preservation of PC (diacyl-16:0/16:0) may be the result of spinal sensory neurons being unaffected in ALS. Taken together, these findings suggest that ALS spinal cords show significant alterations in PC metabolism only at the terminal stage of the disease, and that these changes are confined to specific anatomical regions and cell types.
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J Magn Reson Imaging · May 2015
Reduced structural connectivity within a prefrontal-motor-subcortical network in amyotrophic lateral sclerosis.
To investigate white matter structural connectivity changes associated with amyotrophic lateral sclerosis (ALS) using network analysis and compare the results with those obtained using standard voxel-based methods, specifically Tract-based Spatial Statistics (TBSS). ⋯ These findings suggest that white matter degeneration in ALS is strongly linked to the motor cortex, and that impaired structural networks identified using NBS have a strong correspondence to affected white matter tracts identified using more conventional voxel-based methods.