Fiber-specific white matter reductions in amyotrophic lateral sclerosis

Impaired glymphatic function in the early stages of disease in a TDP-43 mouse model of amyotrophic lateral sclerosis

“…The corticospinal tract is the major neuronal pathway controlling movement and has previously been implicated in DWI studies of ALS [ 13 , 24 , 25 , 39 ]. Using connectivity-based fixel analysis, a whole-brain exploratory method, we found significantly reduced FDC in the left corticospinal tract of TDP-43 mice over time.…”

Segmental alterations of the corpus callosum in motor neuron disease: A DTI and texture analysis in 575 patients

“…With respect to DTI analysis, the identification of the signature of FA decrease relative to healthy controls in the motor callosal fibres in ‘classical‘ ALS was also consistent with a previous study by Spinelli and colleagues ( Spinelli et al, 2020 ) who argued that WM microstructural rearrangements occur early in ALS disease course and that once WM degeneration of the callosal fibres has started, this tends towards a greater rate of deterioration ( Spinelli et al, 2020 ). Additionally, by use of a fixel-based analytical method, patients with ALS showed decreased fibre density values (assessing WM microstructural changes), as well as decreased fibre-bundle cross-section (assessing WM macrostructural changes) and decreased fibre density and cross-section values (assessing both microstructural and macrostructural changes) in the middle posterior body of the CC as compared with healthy controls ( Cheng et al, 2020 ). Our approach, however, combined the DTI data with texture measures derived from structural T1w MRI by a SVM and could, thus, substantially increase the discrimination sensitivity and specificity of MND patients and controls.…”

Neuropathology and neuroanatomy of TDP-43 amyotrophic lateral sclerosis

“…Clearly, although the morphology and regional distribution of pTDP-43 aggregates within selected types of cells have received much attention, the pTDP-43 inclusions alone cannot adequately explain the pathogenesis of sALS [80]. This is perhaps best exemplified by conflicting findings in the corpus callosum, which displays prominent anomalies in neurophysiological and neuroimaging studies, although pTDP-43 disease there is nonexistent or rare [74,[81][82][83][84][85], and by the fact that interneurons (i.e. local circuit neurons with short axons) do not develop pTDP inclusions, although they may also be lost in parallel with a-motor neurons in ALS [86] (Table 1).…”