Neurodegenerative patterns in Wilson disease with hepatic or neurological manifestation assessed by morphometric magnetic resonance imaging

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.

Publication History

Article published online:
26 May 2020