Everolimus alters white matter diffusion in tuberous sclerosis complex

Jan-Mendelt Tillema, James L. Leach, Darcy A. Krueger, David Neal Franz

Research output: Contribution to journalArticle

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Abstract

Objective: Diffusion tensor imaging (DTI) analysis was performed on patients with tuberous sclerosis complex (TSC) to investigate potential changes in normal-appearing white matter after treatment with everolimus, a mammalian target of rapamycin (mTOR) inhibitor. Methods: Recently, a phase I/II trial of everolimus demonstrated significant reductions in sub-ependymal giant cell astrocytoma (SEGA) volume and decreased seizure frequency. Subgroup analysis was performed on DTI data available from this study. TSC patients with SEGA received everolimus, titrated to tolerability to achieve target trough concentrations of 5-15 ng/mL. DTI (1.5 T, 15 directions) was used to calculate fractional anisotropy (FA) and axial, radial, and mean diffusivity within regions of interest (ROIs). Baseline scans were compared to 12-18 months post-treatment and compared to a TSC age- and gender-matched nontreatment control cohort. Results: Of 28 enrolled patients, 20 had sufficient DTI data. Comparing baseline values with those acquired 12-18 months after treatment, a significant change in FA was observed in the corpus callosum, internal capsule, and geniculo-calcarine region (p < 0.05). Mean change in FA was 0.04 (p < 0.01), driven primarily by a significant decrease in radial diffusivity. Mean diffusivity of the combined ROIs decreased slightly (p < 0.05), axial diffusivity remained stable. The control group showed no change over time. Conclusion: Significant changes in FA and radial diffusivity were observed after treatment with everolimus in patients with TSC, suggesting that the genetic defect of TSC in the brain may be modified pharmacologically, even in normal-appearing white matter.

Original languageEnglish (US)
Pages (from-to)526-531
Number of pages6
JournalNeurology
Volume78
Issue number8
DOIs
StatePublished - Feb 21 2012
Externally publishedYes

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Tuberous Sclerosis
Diffusion Tensor Imaging
Anisotropy
Astrocytoma
Giant Cells
Internal Capsule
Corpus Callosum
Sirolimus
Therapeutics
Cell Size
Seizures
Everolimus
White Matter
Control Groups
Imaging
Brain

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Everolimus alters white matter diffusion in tuberous sclerosis complex. / Tillema, Jan-Mendelt; Leach, James L.; Krueger, Darcy A.; Franz, David Neal.

In: Neurology, Vol. 78, No. 8, 21.02.2012, p. 526-531.

Research output: Contribution to journalArticle

Tillema, Jan-Mendelt ; Leach, James L. ; Krueger, Darcy A. ; Franz, David Neal. / Everolimus alters white matter diffusion in tuberous sclerosis complex. In: Neurology. 2012 ; Vol. 78, No. 8. pp. 526-531.
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