Cerebral gray and white matter volume changes and clinical course in metachromatic leukodystrophy (MLD)

Introduction: Metachromatic leukodystrophy (MLD) is a rare lysosomal disorder leading to demyelination and consecutively to a rapid neurological deterioration. The aim of this study was to quantify cerebral volumetric changes in this disorder.

Patients and Methods: A total of 18 patients with late-infantile MLD and 48 typically developing children of the same age range were analyzed and cerebral gray matter (GM) and white matter (WM) volumes were assessed. Within the WM of the patients, the “demyelination load” (volume of demyelinated WM) was quantified.

Results: WM volumes of the patients did not differ from controls. Their GM volume, however, was clearly reduced (p < 0.001). The demyelination load correlated positively with motor deterioration (p < 0.001) and disease duration (p < 0.003).

Conclusion: This supports the notion that besides demyelination, neuronal dysfunction caused by neuronal storage plays an additional role in the disease process. The demyelination load was used as noninvasive imaging marker for disease progression and for therapeutic intervention (stem cell transplantation).

References

Groeschel S, I Dali C, Clas P, et al. Cerebral gray and white matter changes and clinical course in metachromatic leukodystrophy. Neurology 2012;79:1662 – 1670

Krägeloh-Mann I, Groeschel S, Kehrer C, et al. Juvenile metachromatic leukodystrophy 10 years post transplant compared with a non-transplanted cohort. Bone Marrow Transplantation 2012;48:369 – 375