title: Motor pathway degeneration in young ataxia telangiectasia patients: A diffusion tractography study.
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.
authors.affiliation: University of Queensland, School of Medicine, Brisbane, Australia.
authors.forename: Ishani
authors.initials: I
authors.lastname: Sahama
authors.affiliation: Neurology, The Royal Children's Hospital, Brisbane, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Sinclair
authors.affiliation: IRCCS Stella Maris, Calambrone, Pisa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Fiori
authors.affiliation: Digital Productivity Flagship/The Australian E-Health Research Centre, Commonwealth Scientific and Industrial Research Organization, Brisbane, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Doecke
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Pannek
authors.affiliation: Digital Productivity Flagship/The Australian E-Health Research Centre, Commonwealth Scientific and Industrial Research Organization, Brisbane, Australia.
authors.forename: Lee
authors.initials: L
authors.lastname: Reid
authors.affiliation: University of Queensland Centre for Clinical Research, Brisbane, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Lavin
authors.affiliation: Digital Productivity Flagship/The Australian E-Health Research Centre, Commonwealth Scientific and Industrial Research Organization, Brisbane, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rose
mesh_terms: D000293:Adolescent; D000328:Adult; D001260:Ataxia Telangiectasia / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D004525:Efferent Pathways / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: Ataxia telangiectasia; Cerebellum; Diffusion magnetic resonance imaging; Whole tract statistics