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Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
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Everolimus alters white matter diffusion in tuberous sclerosis complex.

Jan-Mendelt Tillema1, James L Leach, Darcy A Krueger

  • 1Department of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Neurology
|January 21, 2012
PubMed
Summary

Everolimus treatment in tuberous sclerosis complex (TSC) patients showed significant white matter changes. Diffusion tensor imaging revealed altered fractional anisotropy and radial diffusivity in normal-appearing white matter.

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Area of Science:

  • Neuroimaging
  • Neurology
  • Pharmacology

Background:

  • Tuberous sclerosis complex (TSC) is a genetic disorder affecting multiple organs, including the brain.
  • Subependymal giant cell astrocytomas (SEGAs) and seizures are common neurological manifestations in TSC.
  • Everolimus, an mTOR inhibitor, has shown efficacy in reducing SEGA volume and seizure frequency in TSC patients.

Purpose of the Study:

  • To investigate changes in normal-appearing white matter using diffusion tensor imaging (DTI) in patients with TSC treated with everolimus.
  • To assess the impact of everolimus on white matter microstructure in TSC.

Main Methods:

  • Subgroup analysis of DTI data from a phase I/II trial of everolimus in TSC patients with SEGA.
  • DTI parameters (fractional anisotropy, axial, radial, and mean diffusivity) were calculated in regions of interest.

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  • Baseline DTI scans were compared to scans obtained 12-18 months post-treatment and to a control group.

    • Main Results:

    • Significant changes in fractional anisotropy (FA) were observed in the corpus callosum, internal capsule, and geniculo-calcarine region after everolimus treatment (p < 0.05).
    • The mean change in FA was 0.04 (p < 0.01), primarily due to a decrease in radial diffusivity.
    • Mean diffusivity showed a slight decrease (p < 0.05), while axial diffusivity remained stable. No changes were observed in the control group.

    Conclusions:

    • Everolimus treatment led to significant alterations in FA and radial diffusivity in the normal-appearing white matter of TSC patients.
    • These findings suggest that everolimus may pharmacologically modify the underlying genetic defect of TSC in the brain's white matter.