Background Clinical presentation of Wilson disease (WD) is heterogeneous and includes hepatic
and neurologic disease manifestations. Genotype-phenotype correlations failed to identify
factors associated with disease expression. WD is known to cause specific qualitative
neuroradiologic changes with hypo-intensities in basal ganglia. The aim of the present
study was to test if WD patients with predominantly hepatic or neurological phenotypic
presentation show quantitative differences when MRI results were analyzed by automated
whole-brain segmentation procedure.
Methods Segmentation of subcortical regions from T1-weighted 3-D-structural MRI data and
estimation of structure volumes were carried out using the FreeSurfer tool (version
6.0, http://surfer.nmr.mgh.harvard.edu/). The volumes of the specific brain regions
were expressed as Z-scores to correct for age and gender specific variations in the
volume of specific brain segments. The study included 20 patients diagnosed with WD
(13 patients with hepatic and 7 with neurologic WD).
Results Patients with predominantly neurological presentation showed a significant reduction
in age and sex-adjusted volume of the caudate (z-score -4.64 vs -0.93, p = 0.024)
and the putamen (z-score -3.72 vs -1.52, p = 0.014) when compared with the group of
patients with predominantly hepatic disease manifestation. In contrast, the latter
showed a significant reduction of the middle cerebellar peduncle volume (z-score -1.20
vs -0.65, p = 0.024). When all patients were compared with age and sex-matched controls,
significantly reduced volumes in several brain regions could be identified. The most
severe neurodegeneration was present in cerebellar white matter, the pallidum and
cerebellar cortex. In most severely affected brain regions no difference between patients
with hepatic and neurologic disease manifestations were noted.
Conclusion This is the first study to quantitative evaluate segmentation of subcortical regions
in patients with WD. Although distinct changes were present in basal ganglia of patients
with neurologic or hepatic WD, our findings indicate that WD is associated with more
general pattern of neurodegeneration in patients with WD.
