Article Text

PDF
Letter
Tissue atrophy and elevated iron concentration in the extrapyramidal motor system in Friedreich ataxia: the IMAGE-FRDA study
  1. Ian H Harding1,
  2. Parnesh Raniga2,
  3. Martin B Delatycki1,3,4,
  4. Monique R Stagnitti1,
  5. Louise A Corben1,3,5,
  6. Elsdon Storey6,
  7. Nellie Georgiou-Karistianis1,
  8. Gary F Egan2
  1. 1 School of Psychological Sciences & Monash Institute of Cognitive and Clinical Neuroscience, Monash University, Melbourne, Victoria, Australia
  2. 2 Monash Biomedical Imaging, Monash University, Melbourne, Victoria, Australia
  3. 3 Bruce Lefroy Centre, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
  4. 4 Department of Clinical Genetics, Austin Health, Melbourne, Victoria, Australia
  5. 5 Monash Medical Centre, Monash Health, Melbourne, Victoria, Australia
  6. 6 Department of Medicine, Monash University, Melbourne, Victoria, Australia
  1. Correspondence to Dr Ian H Harding, School of Psychological Sciences, Level 5, 18 Innovation Walk, Monash University, Melbourne, VIC 3800, Australia; ian.harding{at}monash.edu

Statistics from Altmetric.com

Introduction

Friedreich ataxia (FRDA) is an autosomal recessive disorder defined by progressive motor incoordination. FRDA results from reduced expression of the protein, frataxin, which is involved in cellular iron homeostasis and metabolism, antioxidant protection, and iron-sulfur cluster biogenesis. Disruption of one or more of these processes putatively underpins the pathophysiology of FRDA, which manifests in cell death preferentially targeted to tissues with high rates of frataxin transcription.1

In the brain, accumulation or redistribution of iron within, and atrophy of, the cerebellar dentate nuclei have been reported.1–3 The dentate nuclei are iron-laden structures pivotal to movement coordination. However, basal ganglia and midbrain structures also have high iron content, express high levels of frataxin, and play key roles in motor regulation. Furthermore, the dentate nuclei directly innervate the thalamus and red nuclei, and indirectly project to the striatum. This biology motivates the hypothesis that iron-related pathology and/or degeneration within these extrapyramidal stations may also feature in FRDA. To test this hypothesis, we analysed tissue volume and iron concentration within the dentate nuclei, midbrain (red nuclei, substantia nigra), basal ganglia (caudate, putamen and pallidum), and thalami in individuals with FRDA and healthy controls using magnetic resonance imaging (MRI).

Methods

Data collection

Whole-brain 3 T MRI were acquired from 30 individuals with genetically-confirmed FRDA (35.7±12.2 years; 17 males) and 33 healthy controls (36.9±13.1 years; 18 males; see online supplementary table S1): (1) dual-echo gradient-echo (GRE) images: TA=11.5 min; TR=30 ms, TE1=7.38 ms, …

View Full Text

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.