Steenweg, Marjan E.

AbstractObjectiveMetachromatic leukodystrophy (MLD) is an inherited lysosomal disorder due to a deficiency in arylsulfatase A with progressive demyelination and neurological decline. This retrospective MRI study investigated the extent of cortical involvement at time of diagnosis, and clinical correlates to both conventional and regional volumetric measures of brain involvement.Methods3D‐T1‐weighted MRI scans were used to determine cortical thickness and surface‐based cerebral cortical gray matter (GM) and cerebral white matter (WM) volume (GMV and WMV), WM lesions, thalamus, and cerebellum. MRI‐MLD severity scores were obtained from FLAIR images. Associations between clinical and imaging data were examined using correlation coefficients.ResultsTwenty patients with MLD (mean age 13.7 years, range 2–35) and 20 controls (mean age 13.9 years, range 2–40) were included. Compared with control subjects, late‐infantile, and juvenile patients (n = 14) had significantly diminished cerebral cortical GMV and thalamus volume (P < 0.05), but did not differ in WMV and cortical thickness. Adult patients (n = 6) showed significantly reduced GMV, WMV and cortical thickness (all P < 0.05). Regional analysis showed statistically significant cortical thinning in the cingulate gyrus and most pronounced thinning with age in the frontal lobe of MLD patients. Intelligence quotient (IQ) correlated with MRI‐MLD scores (r = −0.87, P < 0.001).InterpretationSignificant cerebral cortical GMV loss is already present in early stages of MLD. IQ correlates with WM severity scores and lesion volume, but not with volumetric measures. In adult presentations, there is more pronounced global atrophy with GMV and WMV loss and accelerated cortical thinning, most prominently in the cingulate gyrus and frontal lobes.