Metachromatic Leukodystrophy: spatial and temporal pattern of MRI changes and their association with motor deterioration

Objectives: Metachromatic Leukodystrophy (MLD) is a rare disorder leading to progressive cerebral demyelination and neurological impairment, especially deterioration of motor function. Standardised MRI and motor function scores, recently introduced for MLD, are applied to a large cohort of patients with MLD in order to characterize the temporal and spatial pattern of MRI changes and their association with motor decline.

Methods: 109 MR images of 64 patients (33 late-infantile, 31 juvenile) were analysed in a both cross-sectional and longitudinal setting. A MR severity scoring system was applied and intra- and interrater reliability were tested. Furthermore, an adaptation of groß motor function measure to MLD was used to assess motor deterioration in the patients.

Results: The temporal and spatial pattern of MR severity scores are found to differ between late-infantile and juvenile patients. For the late-infantile form of MLD MR scores increase uniformly with disease duration and deterioration of motor function. This progression occurs in a very uniform fashion across these patients, within a narrow age range (between 2 and 3.5 years of age). Clear early and late signs could be distinguished on MRI. For the juvenile form MR scores are found to be more variable and can already have high values even at the onset of first symptoms and even in patients with normal or only mild motor deficit.

Conclusions: The MR severity scoring system enables the systematic characterization of the natural course of MRI changes. Understanding these MRI changes and their clinical significance not only gives insight into pathomechanisms in late-infantile and juvenile MLD but are also of prognostic value for patients and allow evaluation of possible therapeutic interventions.