“…These results are consistent with previous DTI correlation analyses between FA and clinical measure of disease severity and progression within the pyramidal system. 2,10,16,46 However, not all previous MR imaging studies reported significant correlations between diffusivity parameters and clinical scores in ALS, 4,7,11,15 probably due to the following: 1) the intrinsic heterogeneity of the pathologic process (in ALS, degeneration of fiber tracts may not be a classic wallerian degeneration in terms of the contribution from intra-and extracellular changes, astrocytosis, disorders of axonal transport, and accumulation of axonal spheroids 29 ); 2) the different clinical characteristics of the patients, with predominantly upper or lower motor neuron signs and different disease duration and disability; 3) the lack of clinical scores highly specific for the detection of UMN impairment (associations between clinical symptoms and pathologic findings are weak because it has been shown that prominent clinical disability may occur even in the absence of impairment of the CSTs, and vice versa) 29 ; and 4) the different methodologies used.…”