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

Sahama I, Sinclair K, Fiori S, Doecke J, Pannek K, Reid L, Lavin M, Rose S - Neuroimage Clin (2015)

Bottom Line: 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.Mean diffusivity was significantly elevated in anterior tract locations but was reduced within cerebellar peduncle regions of all patient tracts (p < 0.001).In addition, reduced apparent fiber density in the left and right corticospinal and right somatosensory tracts (p < 0.006) occurred in patients.

View Article: PubMed Central - PubMed

Affiliation: University of Queensland, School of Medicine, Brisbane, Australia.

ABSTRACT

Background: Our 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.

Methods: Diffusion 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.

Results: Reduced 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.

Conclusions: Whole 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.

No MeSH data available.


Related in: MedlinePlus

Smooth estimates of the average mean diffusivity (MD) of all controls (blue) and patients (red) are plotted versus position from tract origin (cerebral motor cortex (0%) − cerebellar peduncles (100%)), faceted by tract name (corticospinal (CST), somatosensory (Somato), cortico-ponto-cerebellar (CPC), cerebellar-thalamo-cortical (CTC)) and hemisphere (left (L) and right (R) ± pointwise 99% confidence range (light gray shading)). Tract position at 0–5% represents precentral and postcentral gyrus layers, at 47–58% represents thalamic layers in all tracts and at 95–100% represents the spinal cord in CST and somatosensory tracts, and position of the medial cerebellar and superior cerebellar peduncles connecting the brainstem and cerebellum for the CPC and CTC tracts respectively. ‘N’ denotes tract locations with non-significant values.
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f0020: Smooth estimates of the average mean diffusivity (MD) of all controls (blue) and patients (red) are plotted versus position from tract origin (cerebral motor cortex (0%) − cerebellar peduncles (100%)), faceted by tract name (corticospinal (CST), somatosensory (Somato), cortico-ponto-cerebellar (CPC), cerebellar-thalamo-cortical (CTC)) and hemisphere (left (L) and right (R) ± pointwise 99% confidence range (light gray shading)). Tract position at 0–5% represents precentral and postcentral gyrus layers, at 47–58% represents thalamic layers in all tracts and at 95–100% represents the spinal cord in CST and somatosensory tracts, and position of the medial cerebellar and superior cerebellar peduncles connecting the brainstem and cerebellum for the CPC and CTC tracts respectively. ‘N’ denotes tract locations with non-significant values.

Mentions: A significant increase in MD in all A–T WM pathways was recorded at the level of the cerebral cortex (0%–50% of tract length), however, a paradoxical decrease in MD was observed at the level of the cerebellar peduncles (50%–100% of tract length) in all tracts (p < 0.001, Fig. 4). To cross-check the decrease in MD, a cross-examination of ROIs at the cerebral (precentral and postcentral gyrus) and cerebellar peduncle levels in patients and controls was conducted and revealed neither an increase nor decrease in MD at the cerebral and cerebellar levels in these ROIs respectively, in patients (data not shown). In addition, static change in average MD magnitude (approximated to two decimal places and averaged across age) between the control and patient groups was observed along all analyzed corticomotor tracts (Inline supplementary material Table 2). Areas of non-significant MD change in the right CPC tract at 32% of the tract length and in the right CTC tract at 0% and 37% of the tract length were observed in patients (Fig. 4, denoted by ‘N’).


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

Sahama I, Sinclair K, Fiori S, Doecke J, Pannek K, Reid L, Lavin M, Rose S - Neuroimage Clin (2015)

Smooth estimates of the average mean diffusivity (MD) of all controls (blue) and patients (red) are plotted versus position from tract origin (cerebral motor cortex (0%) − cerebellar peduncles (100%)), faceted by tract name (corticospinal (CST), somatosensory (Somato), cortico-ponto-cerebellar (CPC), cerebellar-thalamo-cortical (CTC)) and hemisphere (left (L) and right (R) ± pointwise 99% confidence range (light gray shading)). Tract position at 0–5% represents precentral and postcentral gyrus layers, at 47–58% represents thalamic layers in all tracts and at 95–100% represents the spinal cord in CST and somatosensory tracts, and position of the medial cerebellar and superior cerebellar peduncles connecting the brainstem and cerebellum for the CPC and CTC tracts respectively. ‘N’ denotes tract locations with non-significant values.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561673&req=5

f0020: Smooth estimates of the average mean diffusivity (MD) of all controls (blue) and patients (red) are plotted versus position from tract origin (cerebral motor cortex (0%) − cerebellar peduncles (100%)), faceted by tract name (corticospinal (CST), somatosensory (Somato), cortico-ponto-cerebellar (CPC), cerebellar-thalamo-cortical (CTC)) and hemisphere (left (L) and right (R) ± pointwise 99% confidence range (light gray shading)). Tract position at 0–5% represents precentral and postcentral gyrus layers, at 47–58% represents thalamic layers in all tracts and at 95–100% represents the spinal cord in CST and somatosensory tracts, and position of the medial cerebellar and superior cerebellar peduncles connecting the brainstem and cerebellum for the CPC and CTC tracts respectively. ‘N’ denotes tract locations with non-significant values.
Mentions: A significant increase in MD in all A–T WM pathways was recorded at the level of the cerebral cortex (0%–50% of tract length), however, a paradoxical decrease in MD was observed at the level of the cerebellar peduncles (50%–100% of tract length) in all tracts (p < 0.001, Fig. 4). To cross-check the decrease in MD, a cross-examination of ROIs at the cerebral (precentral and postcentral gyrus) and cerebellar peduncle levels in patients and controls was conducted and revealed neither an increase nor decrease in MD at the cerebral and cerebellar levels in these ROIs respectively, in patients (data not shown). In addition, static change in average MD magnitude (approximated to two decimal places and averaged across age) between the control and patient groups was observed along all analyzed corticomotor tracts (Inline supplementary material Table 2). Areas of non-significant MD change in the right CPC tract at 32% of the tract length and in the right CTC tract at 0% and 37% of the tract length were observed in patients (Fig. 4, denoted by ‘N’).

Bottom Line: 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.Mean diffusivity was significantly elevated in anterior tract locations but was reduced within cerebellar peduncle regions of all patient tracts (p < 0.001).In addition, reduced apparent fiber density in the left and right corticospinal and right somatosensory tracts (p < 0.006) occurred in patients.

View Article: PubMed Central - PubMed

Affiliation: University of Queensland, School of Medicine, Brisbane, Australia.

ABSTRACT

Background: Our 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.

Methods: Diffusion 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.

Results: Reduced 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.

Conclusions: Whole 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.

No MeSH data available.


Related in: MedlinePlus