Longitudinal Changes in White Matter Fractional Anisotropy in Adult-Onset Niemann-Pick Disease Type C Patients Treated with Miglustat

  • Elizabeth A. Bowman
  • Dennis Velakoulis
  • Patricia Desmond
  • Mark Walterfang
Research Report
Part of the JIMD Reports book series (JIMD, volume 39)

Abstract

Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. This longitudinal diffusion tensor imaging (DTI) study examined how the rate of white matter change differed between treated and non-treated adult-onset NPC patient groups. Nine adult-onset NPC patients (seven undergoing treatment with miglustat, two not treated) underwent DTI neuroimaging. Rates of change in white matter structure as indexed by Tract-Based Spatial Statistics (TBSS) of fractional anisotropy were compared between treated and untreated patients. Treated patients were found to have a significantly slower rate of white matter change in the corticospinal tracts, the thalamic radiation and the inferior longitudinal fasciculus. This is further evidence that miglustat treatment may have a protective effect on white matter structure in the adult-onset form of the disease.

Keywords

Diffusion tensor imaging Fractional anisotropy Miglustat Niemann-Pick type C White matter 

References

  1. Bowman EA et al (2015) Longitudinal changes in cerebellar and subcortical volumes in adult-onset Niemann-Pick disease type C patients treated with miglustat. J Neurol 262:2106–2114CrossRefPubMedGoogle Scholar
  2. German DC et al (2002) Neurodegeneration in the Niemann-Pick C mouse: glial involvement. Neuroscience 109:437–450CrossRefPubMedGoogle Scholar
  3. Goodrum JF, Pentchev PG (1997) Cholesterol reutilization during myelination of regenerating PNS axons is impaired in Niemann-Pick disease type C mice. J Neurosci Res 49:389–392CrossRefPubMedGoogle Scholar
  4. Lee R et al (2014) Corpus callosum diffusion tensor imaging and volume measures are associated with disease severity in pediatric Niemann-Pick disease type C1. Pediatr Neurol 51:669–674. e5CrossRefPubMedPubMedCentralGoogle Scholar
  5. March PA et al (1997) GABAergic neuroaxonal dystrophy and other cytopathological alterations in feline Niemann-Pick disease type C. Acta Neuropathol 94:164–172CrossRefPubMedGoogle Scholar
  6. Masingue M et al (2017) Evolution of structural neuroimaging biomarkers in a series of adult patients with Niemann-Pick type C under treatment. Orphanet J Rare Dis 12:22CrossRefPubMedPubMedCentralGoogle Scholar
  7. Patterson MC et al (2007) Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study. Lancet Neurol 6:765–772CrossRefPubMedGoogle Scholar
  8. Sarna JR et al (2003) Patterned purkinje cell degeneration in mouse models of Niemann-Pick type C disease. J Comp Neurol 456:279–291CrossRefPubMedGoogle Scholar
  9. Scheel M et al (2010) Eye movement and diffusion tensor imaging analysis of treatment effects in a Niemann-Pick Type C patient. Mol Genet Metab 99(3):291–295CrossRefPubMedGoogle Scholar
  10. Sedel F et al (2016) Normalisation of brain spectroscopy findings in Niemann-Pick disease type C patients treated with miglustat. J Neurol 263:927–936CrossRefPubMedPubMedCentralGoogle Scholar
  11. Sevin M et al (2007) The adult form of Niemann-Pick disease type C. Brain 130:120–133CrossRefPubMedGoogle Scholar
  12. Smith SM et al (2004) Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23(Suppl 1):S208–S219CrossRefPubMedGoogle Scholar
  13. Stein VM et al (2012) Miglustat improves purkinje cell survival and alters microglial phenotype in feline Niemann-Pick disease type C. J Neuropathol Exp Neurol 71:434–448CrossRefPubMedPubMedCentralGoogle Scholar
  14. Suzuki K et al (1995) Neurofibrillary tangles in Niemann-Pick disease type C. Acta Neuropathol 89:227–238CrossRefPubMedGoogle Scholar
  15. Taniguchi M et al (2001) Sites and temporal changes of gangliosides GM1/GM2 storage in the Niemann-Pick disease type C mouse brain. Brain and Development 23:414–421CrossRefPubMedGoogle Scholar
  16. Walterfang M et al (2006) The neuropsychiatry of Niemann-Pick type C disease in adulthood. J Neuropsychiatry Clin Neurosci 18:158–170CrossRefPubMedGoogle Scholar
  17. Walterfang M et al (2010) White and gray matter alterations in adults with Niemann-Pick disease type C: a cross-sectional study. Neurology 75:49–56CrossRefPubMedGoogle Scholar
  18. Walterfang M et al (2011) Size and shape of the corpus callosum in adult Niemann-Pick type C reflects state and trait illness variables. AJNR Am J Neuroradiol 32:1340–1346CrossRefPubMedGoogle Scholar
  19. Walterfang M et al (2013) Cerebellar volume correlates with saccadic gain and ataxia in adult Niemann-Pick type C. Mol Genet Metab 108:85–89CrossRefPubMedGoogle Scholar
  20. Winkler AM et al (2014) Permutation inference for the general linear model. NeuroImage 92:381–397CrossRefPubMedPubMedCentralGoogle Scholar
  21. Zervas M et al (2001) Neurons in Niemann-Pick disease type C accumulate gangliosides as well as unesterified cholesterol and undergo dendritic and axonal alterations. J Neuropathol Exp Neurol 60:49–64CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Elizabeth A. Bowman
    • 1
  • Dennis Velakoulis
    • 2
    • 3
  • Patricia Desmond
    • 4
    • 5
  • Mark Walterfang
    • 2
    • 3
    • 6
  1. 1.Brain, Mind and Markets LaboratoryUniversity of MelbourneMelbourneAustralia
  2. 2.Neuropsychiatry UnitRoyal Melbourne HospitalMelbourneAustralia
  3. 3.Melbourne Neuropsychiatry CentreUniversity of MelbourneMelbourneAustralia
  4. 4.Department of RadiologyUniversity of MelbourneMelbourneAustralia
  5. 5.Department of RadiologyRoyal Melbourne HospitalMelbourneAustralia
  6. 6.Florey Institute of Neurosciences and Mental HealthMelbourneAustralia

Personalised recommendations