Cockayne syndrome (CS) is a rare disorder characterized by severe brain atrophy, white matter (WM) hypomyelination and basal ganglia calcifications. This study aimed to quantify atrophy and WM abnormalities using diffusion tensor imaging (DTI) and volumetric analysis, to evaluate possible differences between CS subtypes and to determine whether DTI findings may correspond to a hypomyelinating disorder.
14 patients with CS and 14 controls underwent brain MRI including DTI and a volumetric three-dimensional T1 weighted sequence. DTI analysis was made through regions of interest within the whole brain to obtain fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and in the left centrum semiovale to obtain DTI eigenvalues. The Student's t-test was used to compare patients and controls, and CS subtypes. Given the small number of patients with CS, they were pooled into two groups: moderate (CS1/CS3) and severe (CS2/cerebro-oculo-facio-skeletal syndrome).
Total brain volume in CS was reduced by 57%, predominantly in the infratentorial area (68%) (p < 0.001). Total brain volume reduction was greater in the severe group, but there was no difference in the degree of infratentorial atrophy in the two groups (p = 0.7). Mean FA values were lower, whereas ADC was higher in most of the WM in patients with CS (p < 0.05). ADC in the splenium of the corpus callosum and the posterior limb of the internal capsule and FA in the cerebral peduncles were significantly different between the two groups (p < 0.05). Mean ADC values corresponded to a hypomyelinating disorder. All DTI eigenvalues were higher in patients with CS, mainly for transverse diffusivity (+51%) (p < 0.001).
DTI and volumetric analysis provide quantitative information for the characterization of CS and may be particularly useful for evaluating therapeutic intervention. Advances in knowledge: DTI combined with volumetric analysis provides additional information useful for not only the characterization of CS and distinction of clinical subtypes but also monitoring of therapeutic interventions.