Neurodegenerative process in amyotrophic lateral sclerosis (ALS) has been proven to involve several cortical and subcortical brain regions within and beyond motor areas. However, how ALS pathology spreads progressively during disease evolution is still unknown. In this cross-sectional study we investigated 54 ALS patients, divided into 3 subsets according to the clinical stage, and 18 age and sex-matched healthy controls, by using tract-based spatial statistics (TBSS) diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) analyses. We aimed to identify white (WM) and gray matter (GM) patterns of disease distinctive of each clinical stage, corresponding to specific clinical milestones. ALS cases in stage 2A (i.e., at diagnosis) were characterized by GM and WM impairment of left motor and premotor cortices and brainstem at ponto-mesenchephalic junction. ALS patients in clinical stage 2B (with impairment of two functional regions) exhibited decreased fractional anisotropy (FA) (p<0.001, uncorrected) and increased mean (MD) and radial diffusivity (RD) (p<0.001, uncorrected) in the left cerebellar hemisphere and brainstem precerebellar nuclei, as well as in motor areas, while GM atrophy (p<0.001, uncorrected) was detected only in the left inferior frontal gyrus and right cuneus. Finally, ALS patients in stage 3 (with impairment of three functional regions) exhibited decreased FA and increased MD and RD (p<0.05, corrected) within WM underneath bilateral pre and postcentral gyri, corpus callosum midbody, long associative tracts and midbrain, while no significant clusters of GM atrophy were observed. Our findings reinforce the hypothesis that the neurodegenerative process propagates along the axonal pathways and develops beyond motor areas from early stages, involving progressively several frontotemporal regions and their afferents and efferents, while the detection of GM atrophy in earlier stages and its disappearance in later stages may be the result of reactive gliosis.
Pubmed ID: 25793718 RIS Download
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Software package for analysis of brain imaging data sequences. Sequences can be a series of images from different cohorts, or time-series from same subject. Current release is designed for analysis of fMRI, PET, SPECT, EEG and MEG.
View all literature mentionsSoftware library of image analysis and statistical tools for fMRI, MRI and DTI brain imaging data. Include registration, atlases, diffusion MRI tools for parameter reconstruction and probabilistic taractography, and viewer. Several brain atlases, integrated into FSLView and Featquery, allow viewing of structural and cytoarchitectonic standard space labels and probability maps for cortical and subcortical structures and white matter tracts. Includes Harvard-Oxford cortical and subcortical structural atlases, Julich histological atlas, JHU DTI-based white-matter atlases, Oxford thalamic connectivity atlas, Talairach atlas, MNI structural atlas, and Cerebellum atlas.
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