title: White and gray matter alterations in adults with Niemann-Pick disease type C: a cross-sectional study.
abstract: OBJECTIVE
  Niemann-Pick disease type C (NPC) is a progressive neurovisceral disorder with disrupted intracellular cholesterol metabolism that results in significant alterations to neuronal and axonal structure. Adult patients present with ataxia, gaze palsy, impaired cognition, and neuropsychiatric illness, but the neural substrate has not been well-characterized in vivo. Our aim was to investigate a well-characterized sample of adults with confirmed NPC for gray and white matter abnormalities.
  
  
  METHODS
  We utilized a combination of optimized voxel-based morphometry of T1-weighted images and tract-based spatial statistics of diffusion tensor images to examine gray matter volume and white matter structural differences in 6 adult patients with NPC and 18 gender- and age-matched controls.
  
  
  RESULTS
  Patients with NPC demonstrated bilateral gray matter reductions in large clusters in bilateral hippocampus, thalamus, superior cerebellum, and insula, in addition to smaller regions of inferoposterior cortex. Patients demonstrated widespread reductions in fractional anisotropy in major white matter tracts. Subsequent analysis of measures of axial and radial diffusivity suggest that these changes are contributed to by both impaired myelination and altered axonal structure.
  
  
  CONCLUSIONS
  Findings in gray matter areas are broadly consistent with human and animal studies of selective vulnerability of neuronal populations to the neuropathology of NPC, whereas more widespread white matter changes are consistent with the hypothesis that disrupted myelination and axonal structure predate changes to the neuronal cell body. These findings suggest that volumetric analysis of gray matter and diffusion tensor imaging may be useful modalities for indexing illness stage and monitoring response to emerging treatment.
authors.affiliation: Melbourne Neuropsychiatry Centre & Department of Psychiatry, University of Melbourne and North Western Mental Health Program, Sunshine Hospital and Royal Melbourne Hospital, Melbourne, Australia. mark.walterfang@mh.org.au
authors.forename: M
authors.initials: M
authors.lastname: Walterfang
authors.forename: M
authors.initials: M
authors.lastname: Fahey
authors.forename: P
authors.initials: P
authors.lastname: Desmond
authors.forename: A
authors.initials: A
authors.lastname: Wood
authors.forename: M L
authors.initials: ML
authors.lastname: Seal
authors.forename: C
authors.initials: C
authors.lastname: Steward
authors.forename: C
authors.initials: C
authors.lastname: Adamson
authors.forename: C
authors.initials: C
authors.lastname: Kokkinos
authors.forename: M
authors.initials: M
authors.lastname: Fietz
authors.forename: D
authors.initials: D
authors.lastname: Velakoulis
mesh_terms: D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology*; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D052556:Niemann-Pick Disease, Type C / Q000473:pathology*; D055815:Young Adult