Deep white matter in Huntington's disease

PLoS One. 2014 Oct 23;9(10):e109676. doi: 10.1371/journal.pone.0109676. eCollection 2014.

Abstract

White matter (WM) abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using Magnetic Resonance Imaging (MRI). In the present study, we examined the microstructure of the long-range large deep WM tracts by applying two different MRI approaches: Diffusion Tensor Imaging (DTI) -based tractography, and T2*weighted (iron sensitive) imaging. We collected Pre-HD subjects (n = 25), HD patients (n = 25) and healthy control subjects (n = 50). Results revealed increased axial (AD) and radial diffusivity (RD) and iron levels in Pre-HD subjects compared to controls. Fractional anisotropy decreased between the Pre-HD and HD phase and AD/RD increased and although impairment was pervasive in HD, degeneration occurred in a pattern in Pre-HD. Furthermore, iron levels dropped for HD patients. As increased iron levels are associated with remyelination, the data suggests that Pre-HD subjects attempt to repair damaged deep WM years before symptoms occur but this process fails with disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cerebrum / pathology
  • Demography
  • Diffusion Tensor Imaging
  • Female
  • Humans
  • Huntington Disease / pathology*
  • Male
  • Middle Aged
  • White Matter / pathology*

Grants and funding

This work was supported by the Italian Ministry of Health grant 204/GR-2009-1606835. Also, support was provided by the European Commission: Marie Curie Fellowship for career development to CS (FP7-PEOPLE-2011-IEF). The authors are grateful for the support they received from the Italian Ministry of Health (Ricerca Corrente), European Huntington's Disease Network for the Registry Study, by the “Italian League for Huntington and related diseases onlus (www.lirh.it)” to FS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors are grateful to all patients for contributing to the work.