Interaction between aging and neurodegeneration in amyotrophic lateral sclerosis

Widespread Microstructural White Matter Involvement in Amyotrophic Lateral Sclerosis: A Whole-Brain DTI Study

“…Moreover, this is not the first study in which ALS effects were manifest as lateralized in the motor system. 4,10,15,20,37,43,44 Our findings are also in agreement with the descriptions of asymmetry in ALS pathology of the CSTs, 45 though a correspondence between the side of greater MR imaging differences and the side of greater muscle strength deficit of the limbs was not found, 10 probably because the muscle-strength score is a result of the upper and lower motor neuron involvement, whereas MR imaging detects only the UMN damage.…”

“…35 According to previous neuropathologic findings, 27,34,36 ALS degenerative changes in the cerebral cortex mainly involve motor areas, though recent whole-brain voxel-based morphometry analyses have largely reported GM abnormalities even in extramotor regions. 12,14,15,20,31,37 Thereby, the trends of MD and RD changes, which largely overlapped in our patients in both the genu and splenium of the CC, may represent an increase in the extracellular volume secondary to axonal loss associated with injury to the myelin sheaths, as previously reported in human and animal models of demyelination and axonal degeneration. 2,38,39 Thus, our results also suggest that in advanced stages of ALS, FA changes in the middle body of the CC reflect the degenerative process of axonal damage, inducing loss of motor function, whereas the increase in RD and MD in both the genu and splenium of the CC reflect more subtle axonal damage that could affect fine motor or extramotor skills.…”

Frontotemporal Cortical Thinning in Amyotrophic Lateral Sclerosis

“…Voxel-based morphometry (VBM) allows a fully automated whole-brain measurement of regional brain atrophy by voxelwise comparison of GM and WM volumes between groups of participants. 21 The most consistent finding of VBM studies in ALS involves GM atrophy in several regions of the frontal (ie, anterior cingulate, middle and inferior frontal gyrus) and temporal lobes (ie, temporal poles, superior temporal gyrus, temporal isthmus, hippocampus), [11][12][13]16,17,19 reporting significant correlations between GM atrophy and cognitive dysfunction mainly in patients with an ALS-plus syndrome (ie, ALS with cognitive and behavioral symptoms). 20 However, the lack of agreement on cortical atrophy distribution 22 has prompted the application of other advanced MR imaging approaches.…”

“…[8][9][10] Structural and functional MR imaging studies have corroborated the theory of a relevant frontotemporal impairment in ALS with approximately half of the patients displaying at least mild abnormalities. [11][12][13][14][15][16][17][18][19][20] The development of advanced automated imaging analysis techniques, on the basis of construction of statistical parametric maps, has allowed detailed anatomic studies of brain morphometry. Voxel-based morphometry (VBM) allows a fully automated whole-brain measurement of regional brain atrophy by voxelwise comparison of GM and WM volumes between groups of participants.…”

Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis

“…The sensorimotor network is composed of the primary motor cortex, anterior cingulate cortex, somatosensory regions, and auditory cortex [80]. Others report reduced functional connectivity in the motor network [81,82]. However, several subsequent studies report increased functional activity between the sensorimotor cortex and extramotor regions [83,84], or subregions of either increased or decreased functional coherence within the sensorimotor network [85].…”