title: Assessment of whole-brain white matter by DTI in autosomal recessive spastic ataxia of Charlevoix-Saguenay.
abstract: OBJECTIVE
  Extension and characteristics of WM involvement other than the brain stem remain inadequately investigated in ARSACS. The aim of this study was to investigate whole-brain WM alterations in patients with ARSACS.
  
  
  METHODS
  Nine Turkish unrelated patients with ARSACS and 9 sex- and age-matched healthy control participants underwent neurologic examination, molecular studies, electrophysiologic studies, and DTI of the brain. TBSS was used for whole-brain voxelwise analysis of FA, AD, RD, mean diffusivity of WM. Tractographies for the CST and TPF were also computed.
  
  
  RESULTS
  Molecular studies revealed 8 novel mutations (3 nonsense, 4 missense, and 1 frameshift insertion) and a missense variation in the SACS gene. Thick TPF displaced and compressed the CST in the pons. The TPF had increased FA, decreased RD, and increased AD, which may be attributed to hypertrophy and/or hypermyelination. Widespread decreased FA and increased RD, suggesting demyelination, was found in the limbic, commissural, and projection fibers. In addition to demyelination, CST coursing cranial and caudal to the pons also showed a marked decrease in AD, suggesting axonal degeneration. Electrophysiologic studies revealed findings that concur with demyelination and axonal involvement.
  
  
  CONCLUSIONS
  In addition to developmental changes of the TPF and their effects on the CST in the brain stem, axonal degeneration mainly along the pyramidal tracts and widespread demyelination in WM also occur in patients with ARSACS. Widespread tissue damage may be associated with extensive loss of sacsin protein in the brain and may explain a wide range of progressive neurologic abnormalities in patients with ARSACS.
authors.affiliation: National Magnetic Resonance Research Center, Bilkent University, Bilkent, Ankara, Turkey.
authors.forename: K K
authors.initials: KK
authors.lastname: Oguz
authors.forename: G
authors.initials: G
authors.lastname: Haliloglu
authors.forename: C
authors.initials: C
authors.lastname: Temucin
authors.forename: R
authors.initials: R
authors.lastname: Gocmen
authors.forename: A C
authors.initials: AC
authors.lastname: Has
authors.forename: K
authors.initials: K
authors.lastname: Doerschner
authors.forename: A
authors.initials: A
authors.lastname: Dolgun
authors.forename: M
authors.initials: M
authors.lastname: Alikasifoglu
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D056324:Diffusion Tensor Imaging / Q000379:methods*; D019054:Evoked Potentials, Motor; D005073:Evoked Potentials, Somatosensory; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009128:Muscle Spasticity / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D020125:Mutation, Missense; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011149:Pons / Q000473:pathology / Q000502:physiology; D011712:Pyramidal Tracts / Q000473:pathology* / Q000502:physiology; D020754:Spinocerebellar Ataxias / Q000151:congenital* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D006360:Heat-Shock Proteins; C404403:SACS protein, human