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Metachromatic leukodystrophy: natural course of cerebral MRI changes in relation to clinical course

  • Samuel Groeschel
  • Christiane Kehrer
  • Corinna Engel
  • Christine í Dali
  • Annette Bley
  • Robert Steinfeld
  • Wolfgang Grodd
  • Ingeborg Krägeloh-Mann
Original Article

Abstract

Objective

Metachromatic Leukodystrophy (MLD) is a rare disorder leading to demyelination and neurological impairment. A natural history study within the German leukodystrophy network analyzed MRI changes with respect to the clinical course.

Methods

113 MR images of 68 patients (33 late-infantile, 35 juvenile) were studied cross-sectionally and longitudinally. MRI and motor deterioration were assessed using standardized scoring systems.

Results

The temporal and spatial patterns of MR severity scores differed between the late-infantile and juvenile form. Although early (involving central white matter, corpus callosum) and late signs (involving pons, cerebellum, cerebral atrophy) were similar, high MRI scores (mean 18, SD 1.2, p < 0.001) were evident in the juvenile form already at the onset of first symptoms and even in presymptomatic patients. The progression rate of the MRI score was clearly higher and more uniform in the late-infantile (on average 8 per year, p < 0.0001) than in the juvenile patients (on average 0.4 per year, p < 0.08). In late-infantile patients, MRI changes correlated highly with motor deterioration (rho = 0.73, p < 0.001), this was less remarkable in the juvenile form (rho = 0.50, p < 0.01). Severe motor dysfunction was associated with U-fiber involvement and cerebellar changes (p < 0.05).

Conclusions

MRI showed a typical spatial pattern, which evolved gradually and uniformly during disease progression in late-infantile MLD. In juvenile MLD MRI changes were already observed at disease onset and temporal patterns were more variable. As therapeutic options for MLD are evolving, these findings are not only important for patient counseling but also for the evaluation of therapeutic interventions.

Keywords

Motor Deterioration Cerebral Atrophy Leukodystrophy Arylsulfatase Juvenile Form 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The work was supported by a grant from the German Federal Ministry of Education and Research (LEUKONET). In addition we thank Professor Martin Staudt, Dr Marko Wilke and Professor Thomas Naegele (University Hospital Tübingen, Germany) for participating in the inter-rater test, and Professor Volkmar Gieselmann (Department of Physiology, University of Bonn, Germany, coordinator of the Leukonet) for critical and helpful comments on the manuscript. And we do thank the children and their families for their participation.

Supplementary material

10545_2011_9361_MOESM1_ESM.ppt (38 kb)
Supplementary material Fig. 1 MR Severity score of patients with MLD according to chronological age. Lines connect follow-up scans of patients. Empty circles indicate MR scans of patients before the onset of first symptoms. (PPT 38 kb)
10545_2011_9361_MOESM2_ESM.ppt (58 kb)
Supplementary material Fig. 2 Mean of subscores for the early, middle and late phase of the disease (scaled between 0–1). The numbers indicate specific brain areas depicted by the score. (1 parieto-occipital WM – central, 2 splenium of corpus callosum, 3 frontal WM – central, 4 parieto-occipital WM – periventricular, 5 temporal WM – central, 6 genu of corpus callosum, 7 frontal WM - periventricular, 8 temporal WM – periventricular, 9 pons, 10 parieto-occipital WM – subcortical, 11 posterior limb of internal capsule, 12 frontal WM – subcortical, 13 cerebellar atrophy, 14 cerebellar WM changes, 15 temporal WM – subcortical, 16 cerebral atrophy, 17 anterior limb of internal capsule) (PPT 58 kb)
10545_2011_9361_MOESM3_ESM.doc (25 kb)
Supplementary material Table 1 MR Severity Scoring System for MLD (Eichler et al. 2009). (DOC 25 kb)
10545_2011_9361_MOESM4_ESM.doc (27 kb)
Supplementary material, Table 2 Gross Motor Function Classification system for MLD (GMFC-MLD) (Kehrer et al. 2011b). (DOC 27 kb)
10545_2011_9361_MOESM5_ESM.doc (48 kb)
Supplementary material, Table 3 Correlation coefficients (Spearman’s rank) and their correlation p-value are given for the whole MR Severity Score and its subscores with the motor function score (GMFC-MLD) for the late-infantile and juvenile form of MLD. Highlighted correlation coefficients (in bold font) are remarkably high. (DOC 48 kb)

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Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  • Samuel Groeschel
    • 1
  • Christiane Kehrer
    • 2
  • Corinna Engel
    • 3
  • Christine í Dali
    • 4
  • Annette Bley
    • 5
  • Robert Steinfeld
    • 6
  • Wolfgang Grodd
    • 7
  • Ingeborg Krägeloh-Mann
    • 2
  1. 1.Department of Pediatric Neurology & Developmental Medicine and Experimental Pediatric NeuroimagingUniversity Children’s HospitalTübingenGermany
  2. 2.Department of Pediatric Neurology & Developmental MedicineUniversity Children’s HospitalTübingenGermany
  3. 3.Center for Pediatric Clinical Studies, BiometryUniversity Children’s HospitalTübingenGermany
  4. 4.Department of Clinical Genetics, RigshospitaletCopenhagenDenmark
  5. 5.Children’s HospitalUniversity Medical Center Hamburg-EppendorfHamburg-EppendorfGermany
  6. 6.Department of Pediatrics and Pediatric NeurologyUniversity Hospital GöttingenGöttingenGermany
  7. 7.Department of Psychiatry and PsychotherapyUniversity Hospital AachenAachenGermany

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