Diffusion tensor imaging in metachromatic leukodystrophy

Diane F. van Rappard, Marsh Königs, Marjan E. Steenweg, Jaap Jan Boelens, Jaap Oosterlaan, Marjo S. van der Knaap, Nicole I. Wolf, Petra J.W. Pouwels

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Objective: We aimed to gain more insight into the pathomechanisms of metachromatic leukodystrophy (MLD), by comparing magnitude and direction of diffusion between patients and controls at diagnosis and during follow-up. Methods: Four late-infantile, 16 juvenile and 8 adult onset MLD patients [of which 13 considered eligible for hematopoietic cell transplantation (HCT)] and 47 controls were examined using diffusion tensor imaging. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were quantified and compared between groups using tract-based spatial statistics (TBSS). Diffusion measures were determined for normal-appearing white matter (NAWM), corpus callosum, thalamus (all based on subject-wise segmentation), and pyramidal tracts, determined with probabilistic tractography. Measures were compared between HCT-eligible patients, non-eligible patients and controls using general linear model and nonparametric permutation analyses (randomise) for TBSS data, considering family-wise error corrected p OpenSPiltSPi 0.05 significant. Results: Throughout white matter (WM), FA was decreased and MD and RD increased in both patient groups compared to controls, while AD was decreased in NAWM and corpus callosum. In the thalamus, no differences in FA were observed, but all diffusivities were increased in both patient groups. Differences were most pronounced between controls and patients non-eligible for HCT. Longitudinally (median follow-up 3.9 years), diffusion measures remained relatively stable for HCT-treated patients, but were progressively abnormal for non-eligible patients. Interpretation: The observed diffusion measures confirm that brain microstructure is changed in MLD, reflecting different pathological processes including loss of myelin and sulfatide accumulation. The observation of both increased and decreased AD probably reflects a balance between myelin and axonal loss vs. intracellular sulfatide storage in macrophages, depending on region and disease stage.

Original languageEnglish
Pages (from-to)659-668
Number of pages10
JournalJournal of Neurology
Volume265
Issue number3
Early online date30 Jan 2018
DOIs
Publication statusPublished - Mar 2018

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Metachromatic Leukodystrophy
Diffusion Tensor Imaging
Cell Transplantation
Anisotropy
Sulfoglycosphingolipids
Corpus Callosum
Myelin Sheath
Thalamus
Pyramidal Tracts
Pathologic Processes
Linear Models
Macrophages
Observation

Keywords

  • Axial diffusivity
  • Diffusion weighted imaging
  • Radial diffusivity
  • Sulfatide storage
  • White matter disorder

Cite this

van Rappard, D. F., Königs, M., Steenweg, M. E., Boelens, J. J., Oosterlaan, J., van der Knaap, M. S., ... Pouwels, P. J. W. (2018). Diffusion tensor imaging in metachromatic leukodystrophy. Journal of Neurology, 265(3), 659-668. https://doi.org/10.1007/s00415-018-8765-3
van Rappard, Diane F. ; Königs, Marsh ; Steenweg, Marjan E. ; Boelens, Jaap Jan ; Oosterlaan, Jaap ; van der Knaap, Marjo S. ; Wolf, Nicole I. ; Pouwels, Petra J.W. / Diffusion tensor imaging in metachromatic leukodystrophy. In: Journal of Neurology. 2018 ; Vol. 265, No. 3. pp. 659-668.
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van Rappard, DF, Königs, M, Steenweg, ME, Boelens, JJ, Oosterlaan, J, van der Knaap, MS, Wolf, NI & Pouwels, PJW 2018, 'Diffusion tensor imaging in metachromatic leukodystrophy' Journal of Neurology, vol. 265, no. 3, pp. 659-668. https://doi.org/10.1007/s00415-018-8765-3

Diffusion tensor imaging in metachromatic leukodystrophy. / van Rappard, Diane F.; Königs, Marsh; Steenweg, Marjan E.; Boelens, Jaap Jan; Oosterlaan, Jaap; van der Knaap, Marjo S.; Wolf, Nicole I.; Pouwels, Petra J.W.

In: Journal of Neurology, Vol. 265, No. 3, 03.2018, p. 659-668.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - van Rappard, Diane F.

AU - Königs, Marsh

AU - Steenweg, Marjan E.

AU - Boelens, Jaap Jan

AU - Oosterlaan, Jaap

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AU - Wolf, Nicole I.

AU - Pouwels, Petra J.W.

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KW - Sulfatide storage

KW - White matter disorder

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