TY - JOUR
T1 - Cerebral gray and white matter changes and clinical course in metachromatic leukodystrophy
AU - Groeschel, Samuel
AU - í Dali, Christine
AU - Clas, Philipp
AU - Böhringer, Judith
AU - Duno, Morten
AU - Krarup, Christian
AU - Kehrer, Christiane
AU - Wilke, Marko
AU - Krägeloh-Mann, Ingeborg
PY - 2012/10/16
Y1 - 2012/10/16
N2 - Objective: Metachromatic leukodystrophy (MLD) is a rare metabolic disorder leading to demyelination and rapid neurologic deterioration. As therapeutic options evolve, it seems essential to understand and quantify progression of the natural disease. The aim of this study was to assess cerebral volumetric changes in children with MLD in comparison to normal controls and in relation to disease course. Method: Eighteen patients with late-infantile MLD and 42 typically developing children in the same age range (20-59 months) were analyzed in a cross-sectional study. Patients underwent detailed genetic, biochemical, electrophysiologic, and clinical characterization. Cerebral gray matter (GM) and white matter (WM) volumes were assessed by multispectral segmentation of T1- and T2-weighted MRI. In addition, the demyelinated WM (demyelination load) was automatically quantified in T2-weighted images of the patients, and analyzed in relation to the clinical course. Results: WM volumes of patients did not differ from controls, although their growth curves were slightly different. GM volumes of patients, however, were on average 10.7% (confidence interval 6.0%-14.9%, p < 0.001) below those of normally developing children. The demyelination load (corrected for totalWMvolume) increased with disease duration (p < 0.003) and motor deterioration (p < 0.001). Conclusion: GM volume in patients with MLD is reduced when compared with healthy controls, already at young age. This supports the notion that, beside demyelination, neuronal dysfunction caused by neuronal storage plays an additional role in the disease process. The demyelination load may be a useful noninvasive imaging marker for disease progression and may serve as reference for therapeutic intervention.
AB - Objective: Metachromatic leukodystrophy (MLD) is a rare metabolic disorder leading to demyelination and rapid neurologic deterioration. As therapeutic options evolve, it seems essential to understand and quantify progression of the natural disease. The aim of this study was to assess cerebral volumetric changes in children with MLD in comparison to normal controls and in relation to disease course. Method: Eighteen patients with late-infantile MLD and 42 typically developing children in the same age range (20-59 months) were analyzed in a cross-sectional study. Patients underwent detailed genetic, biochemical, electrophysiologic, and clinical characterization. Cerebral gray matter (GM) and white matter (WM) volumes were assessed by multispectral segmentation of T1- and T2-weighted MRI. In addition, the demyelinated WM (demyelination load) was automatically quantified in T2-weighted images of the patients, and analyzed in relation to the clinical course. Results: WM volumes of patients did not differ from controls, although their growth curves were slightly different. GM volumes of patients, however, were on average 10.7% (confidence interval 6.0%-14.9%, p < 0.001) below those of normally developing children. The demyelination load (corrected for totalWMvolume) increased with disease duration (p < 0.003) and motor deterioration (p < 0.001). Conclusion: GM volume in patients with MLD is reduced when compared with healthy controls, already at young age. This supports the notion that, beside demyelination, neuronal dysfunction caused by neuronal storage plays an additional role in the disease process. The demyelination load may be a useful noninvasive imaging marker for disease progression and may serve as reference for therapeutic intervention.
U2 - 10.1212/WNL.0b013e31826e9ad2
DO - 10.1212/WNL.0b013e31826e9ad2
M3 - Journal article
C2 - 22993277
SN - 0028-3878
VL - 79
SP - 1662
EP - 1670
JO - Neurology
JF - Neurology
IS - 16
ER -