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White and gray matter alterations in adults with Niemann-Pick disease type C: a cross-sectional study

Version 2 2024-06-05, 05:14
Version 1 2019-08-07, 08:49
journal contribution
posted on 2024-06-05, 05:14 authored by M Walterfang, M Fahey, P Desmond, Amanda WoodAmanda Wood, ML Seal, C Steward, C Adamson, C Kokkinos, M Fietz, D Velakoulis
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.

History

Journal

Neurology

Volume

75

Pagination

49-56

Location

Philadelphia, Pa.

ISSN

0028-3878

eISSN

1526-632X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2010, AAN

Issue

1

Publisher

American Academy of Neurology

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