Neuropediatrics 2012; 43 - FV11_09
DOI: 10.1055/s-0032-1307053

Metachromatic Leukodystrophy – cerebral grey and white matter volume changes and clinical course

S Gröschel 1, C i Dali 2, P Clas 1, C Kehrer 3, M Wilke 1, I Krägeloh-Mann 3
  • 1Experimentelle Pädiatrische Neurobildgebung, Neuropädiatrie Unikinderklinik Tübingen, Tübingen, Germany
  • 2Clinical Genetics, Rigshospitalet, Kopenhagen, Kopenhagen, Denmark
  • 3Neuropädiatrie Unikinderklinik Tübingen, Tübingen, Germany

Aims: Metachromatic Leukodystrophy (MLD) is a rare metabolic disorder leading to demyelination and rapid neurological deterioration. As therapeutic options evolve, it seems essential to understand and quantify progression of the natural disease course. The aim of this study was to assess cerebral volumetric changes in comparison to normal controls and in relation to the disease course.

Methods: 18 patients (19 MRIs) with late-infantile MLD and 48 typically developing children of the same age range were analyzed. Cerebral grey matter (GM) and white matter (WM) volumes were assessed by automated multispectral segmentation of T1- and T2-weighted MRI sequences using SPM8. Within the WM of T2-weighted images of the patients, the 'demyelination load' (volume of demyelinated WM) was quantified by applying an automated intensity threshold. These volumetric parameters were validated using manual segmentation and analyzed in relation to the clinical course.

Results: WM volumes of the patients did not differ from controls, although their growth curves appeared different. GM volume of patients, however, was clearly below those of normally developing children (p<0.001). The demyelination load (corrected by the total WM volume) was found to increase after disease onset and correlated positively with motor deterioration (p<0.001) and disease duration (p<0.003). Validation yielded good agreement between manual and automated measurements of the demyelination load.

Conclusion: GM volume in patients with MLD is reduced early during the disease course when compared with healthy controls. This supports the idea that neuronal dysfunction caused by neuronal storage plays an additional role in the disease process besides demyelination. The demyelination load increased with disease duration and motor deterioration and might be a useful parameter for the progression of the disease. These data may serve as reference for therapeutic intervention.

Metachromatic Leukodystrophy - demyelination load - volumetry - MRI