Motor pathway degeneration in young ataxia telangiectasia patients: A diffusion tractography study

Abstract

BackgroundOur understanding of the effect of ataxia–telangiectasia mutated gene mutations on brain structure and function is limited. In this study, white matter motor pathway integrity was investigated in ataxia telangiectasia patients using diffusion MRI and probabilistic tractography.MethodsDiffusion MRI were obtained from 12 patients (age range: 7–22 years, mean: 12 years) and 12 typically developing age matched participants (age range 8–23 years, mean: 13 years). White matter fiber tracking and whole tract statistical analyses were used to assess quantitative fractional anisotropy and mean diffusivity differences along the cortico-ponto-cerebellar, cerebellar-thalamo-cortical, somatosensory and lateral corticospinal tract length in patients using a linear mixed effects model. White matter tract streamline number and apparent fiber density in patient and control tracts were also assessed.ResultsReduced fractional anisotropy along all analyzed patient tracts were observed (p < 0.001). Mean diffusivity was significantly elevated in anterior tract locations but was reduced within cerebellar peduncle regions of all patient tracts (p < 0.001). Reduced tract streamline number and tract volume in the left and right corticospinal and somatosensory tracts were observed in patients (p < 0.006). In addition, reduced apparent fiber density in the left and right corticospinal and right somatosensory tracts (p < 0.006) occurred in patients.ConclusionsWhole tract analysis of the corticomotor, corticospinal and somatosensory pathways in ataxia telangiectasia showed significant white matter degeneration along the entire length of motor circuits, highlighting that ataxia–telangiectasia gene mutation impacts the cerebellum and multiple other motor circuits in young patients.

DNA damage in the oligodendrocyte lineage and its role in brain aging

“…Additional MRI studies have identified hypomyelinated foci in the cerebrum (Ciemins and Horowitz, 2000), as well as in the cerebellum in A-T patients of different ages (Firat et al, 2005). Indeed, MRI-DTI study on a larger cohort of young patients found that the WM tracts projecting to the cortex, including corticomotor, corticospinal and somatosensory pathways, undergo degeneration (Sahama et al, 2015; Sahama et al, 2014). These clinical findings provide evidence that wide-spread defects in myelination and most likely OL function are part of the A-T phenotype that can be found in additional to the neuronal cell death.…”

Structural and functional brain changes following four weeks of unimanual motor training: evidence from fMRI-guided diffusion MRI tractography

“…The nature of axonal 'all-or-nothing' signalling and relationships between activity and subsequent myelination [Demerens et al, 1996;Ishibashi et al, 2006] imply that genuine changes in white matter should occur throughout the entire length of a tract. To confirm that any detected changes reflected genuine change throughout the length of the corticomotor tract, each streamline was binned into seven equal-length sections, using a method previously described [Sahama et al, 2015], and intensities were sampled for each section. An example of this binning is shown in Figure 2.…”

Ataxia telangiectasia: a review

“…In addition to cerebellar atrophy, MRI studies have demonstrated cerebral, white matter abnormalities in older patients, including hemosiderin deposits and deep cerebral telangiectatic vessels, as well as degenerative changes in white matter corticomotor tracts extending from the cerebellum in younger patients with A-T [17–19]. …”