Clinical correlation of brain MRI and MRS abnormalities in patients with Wilson disease.

Abstract

The progression of Wilson disease (WD), a disorder of copper metabolism, can be arrested by chelation therapy. However, neurologic deficits may persist despite adequate treatment. MRI is used to assess patients with WD, but previous attempts to correlate clinical progression with the investigation findings have often been unsuccessful. To identify MR visible markers that could help stratify disease severity and to clarify the mechanism of persistent neurologic deficit after treatment. MRI and proton MR spectroscopy (1H-MRS) were performed in 17 patients with WD. MRI was assessed semiquantitatively and used to locate volumes of interest (voxels) in the striatum for 1H-MRS. MRI showed abnormalities predominantly confined to those patients with neurologic features of WD. The 1H spectra demonstrated a reduction of N-acetylaspartate and N-acetylaspartylglutamate (2.05 mM; p < 0.01) in those patients with neurologic features but not in patients without clinical neurologic involvement (0.42 mM; p > 0.1) in comparison with age-matched normal control subjects. Choline was also reduced in both patient groups (0.08 mM; p < 0.01) compared with age-matched controls. There may be a biochemical correlate of tissue-specific dysfunction in patients with Wilson disease who develop neurologic features. These changes appear to be present despite prior clinical improvement and may imply a need for additional treatment.