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CC BY-NC-ND 4.0 · Neuropediatrics 2023; 54(04): 244-252
DOI: 10.1055/a-2073-4178
Original Article

Clinical Significance of Diffusion Tensor Imaging in Metachromatic Leukodystrophy

Lucas Bastian Amedick
1   Department of Pediatric Neurology and Developmental Medicine, University of Tuebingen, Tuebingen, Germany
,
Pascal Martin 
2   Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University Hospitals Tubingen, Tubingen, Germany
,
Judith Beschle
3   Department of Pediatric Neurology and Developmental Medicine, University Hospital Tübingen, Tuebingen, Germany
,
Manuel Strölin
1   Department of Pediatric Neurology and Developmental Medicine, University of Tuebingen, Tuebingen, Germany
,
Marko Wilke
4   Department of Pediatric Neurology, Children's Hospital, Tübingen, Germany
,
Nicole Wolf 
5   Department of Child Neurology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
,
Petra Pouwels
6   Department of Radiology and Nuclear Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, Noord-Holland, The Netherlands
,
Gisela Hagberg
7   Max-Planck-Institut für Biologische Kybernetik, Tubingen, Baden-Württemberg, Germany
,
Uwe Klose
8   Department of Diagnostic and Interventional Neuroradiology, Radiological Clinic, University of Tübingen, Tübingen, Germany
,
Thomas Naegele
9   Department für Diagnostische und Interventionelle Neuroradiologie, Universitätsklinikum Tübingen, Tubingen, Baden-Württemberg, Germany
,
Ingeborg Kraegeloh-Mann
10   Kinderklinik - University Tübingen, Tübingen, Germany
,
Samuel Groeschel
1   Department of Pediatric Neurology and Developmental Medicine, University of Tuebingen, Tuebingen, Germany
› Author Affiliations Funding The work was supported by an institutional research grant from Takeda Pharma AG (IIR-DEU-002540) and the German Research Foundation (GR 4688/2–1).
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Abstract

Background Metachromatic leukodystrophy (MLD) is a lysosomal enzyme deficiency disorder leading to progressive demyelination and, consecutively, to cognitive and motor decline. Brain magnetic resonance imaging (MRI) can detect affected white matter as T2 hyperintense areas but cannot quantify the gradual microstructural process of demyelination more accurately. Our study aimed to investigate the value of routine MR diffusion tensor imaging in assessing disease progression.

Methods MR diffusion parameters (apparent diffusion coefficient [ADC] and fractional anisotropy [FA]) were in the frontal white matter, central region (CR), and posterior limb of the internal capsule in 111 MR datasets from a natural history study of 83 patients (age: 0.5–39.9 years; 35 late-infantile, 45 juvenile, 3 adult, with clinical diffusion sequences of different scanner manufacturers) as well as 120 controls. Results were correlated with clinical parameters reflecting motor and cognitive function.

Results ADC values increase and FA values decrease depending on disease stage/severity. They show region-specific correlations with clinical parameters of motor and cognitive symptoms, respectively. Higher ADC levels in CR at diagnosis predicted a disease course with more rapid motor deterioration in juvenile MLD patients. In highly organized tissues such as the corticospinal tract, in particular, diffusion MR parameters were highly sensitive to MLD-associated changes and did not correlate with the visual quantification of T2 hyperintensities.

Conclusion Our results show that diffusion MRI can deliver valuable, robust, clinically meaningful, and easily obtainable/accessible/available parameters in the assessment of prognosis and progression of MLD. Therefore, it provides additional quantifiable information to established methods such as T2 hyperintensity.

Keywords

metachromatic leukodystrophy - DTI - ADC - FA - diffusion

Note

S.G., I.K.-M., and N.W. are members of the ERN-RND, project ID 739510.


MRI data used in the preparation of this manuscript were obtained from the National Institute of Mental Health (NIMH) Data Archive (NDA). NDA is a collaborative informatics system created by the NIH to provide a national resource to support and accelerate research in mental health. Dataset identifier(s): DOI 10.15154/1528588. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or of the Submitters submitting original data to NDA.


Ethics Approval

The study was approved by the local ethics committees of the University of Tuebingen, Germany, and VU University Medical Center, Amsterdam, the Netherlands (401/2005 and 2018.300). Written informed consent was given by the parents of the patients or the patients themselves as appropriate.


Supplementary Material



Publication History

Received: 11 July 2022

Accepted: 22 March 2023

Accepted Manuscript online:
13 April 2023

Article published online:
10 May 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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