Motor associations of iron accumulation in deep grey matter nuclei in Parkinson's disease: a cross-sectional study of iron-related magnetic resonance imaging susceptibility

Eur J Neurol. 2017 Feb;24(2):357-365. doi: 10.1111/ene.13208. Epub 2016 Dec 16.

Abstract

Background and purpose: To determine whether iron deposition in deep brain nuclei assessed using high-pass filtered phase imaging plays a role in motor disease severity in Parkinson's disease (PD).

Methods: Seventy patients with mild to moderate PD and 20 age- and gender-matched healthy volunteers (HVs) underwent susceptibility-weighted imaging on a 3 T magnetic resonance imaging scanner. Phase shifts (radians) in deep brain nuclei were derived from high-pass filtered phase images and compared between groups. Analysis of clinical laterality and correlations with motor severity (Unified Parkinson's Disease Rating Scale, Part III, UPDRS-III) were performed. Phase shifts (in radians) were compared between HVs and three PD subgroups divided according to UPDRS-III scores using analysis of covariance, adjusting for age and regional area.

Results: Parkinson's disease patients had significantly (P < 0.001) higher radians than HVs bilaterally in the putamen, globus pallidus and substantia nigra (SN). The SN contralateral to the most affected side showed higher radians (P < 0.001) compared to the less affected side. SN radians positively correlated with UPDRS-III and bradykinesia-rigidity subscores, but not with tremor subscores. ancova followed by post hoc Bonferroni-adjusted pairwise comparisons revealed that SN radians were significantly greater in the PD subgroup with higher UPDRS-III scores compared to both lowest UPDRS-III PD and HV groups (P < 0.001).

Conclusions: Increased nigral iron accumulation in PD appears to be stratified according to disease motor severity and correlates with symptoms related to dopaminergic neurodegeneration. This semi-quantitative in vivo iron assessment could prove useful for objectively monitoring PD progression, especially in clinical trials concerning iron chelation therapies.

Keywords: SWI; Parkinson's disease; iron; motor severity; neurodegeneration.

MeSH terms

  • Adult
  • Aged
  • Cross-Sectional Studies
  • Disease Susceptibility
  • Female
  • Gray Matter / diagnostic imaging
  • Gray Matter / metabolism*
  • Humans
  • Hypokinesia / etiology
  • Hypokinesia / physiopathology
  • Image Processing, Computer-Assisted
  • Iron / metabolism*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Movement Disorders / etiology
  • Movement Disorders / physiopathology*
  • Muscle Rigidity / etiology
  • Muscle Rigidity / physiopathology
  • Parkinson Disease / complications
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / metabolism*
  • Parkinson Disease / physiopathology*
  • Substantia Nigra / diagnostic imaging
  • Substantia Nigra / metabolism

Substances

  • Iron