Journal of Neurology

, Volume 262, Issue 9, pp 2106–2114

Longitudinal changes in cerebellar and subcortical volumes in adult-onset Niemann–Pick disease type C patients treated with miglustat

  • Elizabeth A. Bowman
  • Mark Walterfang
  • Larry Abel
  • Patricia Desmond
  • Michael Fahey
  • Dennis Velakoulis
Original Communication

DOI: 10.1007/s00415-015-7819-z

Cite this article as:
Bowman, E.A., Walterfang, M., Abel, L. et al. J Neurol (2015) 262: 2106. doi:10.1007/s00415-015-7819-z


Niemann–Pick disease type C (NPC) is a rare neurovisceral disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment available to date is miglustat, an iminosugar inhibiting the accumulation of lipid by-products in neurons. This study explored how changes in cerebellar grey and white matter volumes, and in subcortical volumes, related to patient treatment status and disability and ataxia ratings. Nine adult-onset NPC patients and 17 matched controls underwent T1-weighted MRI. One patient was not receiving miglustat, and pre-treatment data were available for a further patient. Semi-automated cerebellar and subcortical segmentation was undertaken, and the rates of change in putamen, hippocampal, thalamic and caudal volumes, and grey and white matter cerebellar volumes, were compared to rates of change in Iturriaga disability score, Brief Ataxia Rating Scale (BARS), and horizontal saccadic gain. Untreated NPC patients appeared to lose cerebellar grey and white matter, bilateral thalamic volume, and right caudate volume faster than treated patients. Cerebellar grey matter volume loss and volume loss in the left thalamus were significantly correlated with Iturriaga disability scale changes. Change in both cerebellar grey and white matter was correlated with decrease in horizontal saccadic gain, but not with change in BARS. This is the first study to examine longitudinal treatment effects of miglustat on cerebellar and subcortical volumes in patients with adult-onset NPC, and is evidence that miglustat may have a protective effect on cerebellar and subcortical structure and function.


Cerebellum Niemann–Pick type C Lysosomal Ataxia Thalamus Saccades 

Funding information

Funder NameGrant NumberFunding Note
Actelion Pharmaceuticals

    Copyright information

    © Springer-Verlag Berlin Heidelberg 2015

    Authors and Affiliations

    • Elizabeth A. Bowman
      • 1
    • Mark Walterfang
      • 2
    • Larry Abel
      • 3
    • Patricia Desmond
      • 4
    • Michael Fahey
      • 5
    • Dennis Velakoulis
      • 6
    1. 1.Department of Medicine, Royal Melbourne Hospital, Melbourne Brain CentreUniversity of MelbourneMelbourneAustralia
    2. 2.Royal Melbourne Hospital, Melbourne Neuropsychiatry CentreUniversity of Melbourne and Melbourne HealthParkvilleAustralia
    3. 3.Department of Optometry and Vision SciencesUniversity of MelbourneMelbourneAustralia
    4. 4.Department of RadiologyThe Royal Melbourne HospitalParkvilleAustralia
    5. 5.Department of PediatricsMonash UniversityClaytonAustralia
    6. 6.Melbourne Neuropsychiatry CentreUniversity of Melbourne and Melbourne HealthParkvilleAustralia

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