Diffusion MRI Captures White Matter Microstructure Alterations in PRKN Disease

J Parkinsons Dis. 2021;11(3):1221-1235. doi: 10.3233/JPD-202495.

Abstract

Background: Although pathological studies usually indicate pure dopaminergic neuronal degeneration in patients with parkin (PRKN) mutations, there is no evidence to date regarding white matter (WM) pathology. A previous diffusion MRI study has revealed WM microstructural alterations caused by systemic oxidative stress in idiopathic Parkinson's disease (PD), and we found that PRKN patients have systemic oxidative stress in serum biomarker studies. Thus, we hypothesized that PRKN mutations might lead to WM abnormalities.

Objective: To investigate whether there are WM microstructural abnormalities in early-onset PD patients with PRKN mutations using diffusion tensor imaging (DTI).

Methods: Nine PRKN patients and 15 age- and sex-matched healthy controls were recruited. DTI measures were acquired on a 3T MR scanner using a b value of 1,000 s/mm2 along 32 isotropic diffusion gradients. The DTI measures were compared between groups using tract-based spatial statistics (TBSS) analysis. Correlation analysis was also performed between the DTI parameters and several serum oxidative stress markers obtained in a previously conducted metabolomic analysis.

Results: Although the WM volumes were not significantly different, the TBSS analysis revealed a corresponding decrease in fractional anisotropy and an increase in mean diffusivity and radial diffusivity in WM areas, such as the anterior and superior corona radiata and uncinate fasciculus, in PRKN patients compared with controls. Furthermore, 9-hydroxystearate, an oxidative stress marker, and disease duration were positively correlated with several parameters in PRKN patients.

Conclusion: This pilot study suggests that WM microstructural impairments occur in PRKN patients and are associated with disease duration and oxidative stress.

Keywords: Diffusion MRI; Parkinson’s disease; magnetic resonance imaging (MRI); metabolomics; oxidative stress.

MeSH terms

  • Case-Control Studies
  • Diffusion Magnetic Resonance Imaging
  • Humans
  • Parkinson Disease* / genetics
  • Parkinson Disease* / pathology
  • Pilot Projects
  • Ubiquitin-Protein Ligases* / genetics
  • White Matter* / diagnostic imaging
  • White Matter* / pathology
  • White Matter* / ultrastructure

Substances

  • Ubiquitin-Protein Ligases