Metachromatic leukodystrophy: natural course of cerebral MRI changes in relation to clinical course
- 928 Downloads
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.
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.
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).
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.
KeywordsMotor Deterioration Cerebral Atrophy Leukodystrophy Arylsulfatase Juvenile Form
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.
- Kehrer C, Blumenstock G, Gieselmann V, and Krägeloh-Mann I (2011a) The natural course of gross motor deterioration in metachromatic leukodystrophy. Dev Med Child Neurol. accepted for publication.Google Scholar
- van der Knaap MS, Valk J (2005) Magnetic resonance in myelin, myelination, and myelin disorders. Springer, Berlin Google Scholar
- von Figura K, Gieselmann V, and Jacken J (2001) Metachromatic leukodystrophy. In Scriver CR, Beaudet AL, Sly WS et al., eds. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill, 3695–3724Google Scholar