Tissue atrophy and elevated iron concentration in the extrapyramidal motor system in Friedreich ataxia: the IMAGE-FRDA study

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

+Author Affiliations

  1. 1School of Psychological Sciences & Monash Institute of Cognitive and Clinical Neuroscience, Monash University, Melbourne, Victoria, Australia
  2. 2Monash Biomedical Imaging, Monash University, Melbourne, Victoria, Australia
  3. 3Bruce Lefroy Centre, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
  4. 4Department of Clinical Genetics, Austin Health, Melbourne, Victoria, Australia
  5. 5Monash Medical Centre, Monash Health, Melbourne, Victoria, Australia
  6. 6Department of Medicine, Monash University, Melbourne, Victoria, Australia
  1. Correspondence toDr Ian H Harding, School of Psychological Sciences, Level 5, 18 Innovation Walk, Monash University, Melbourne, VIC 3800, Australia; ■■■■■■■■■■■■■■■■■■■■■■
  • Received 10 November 2015
  • Revised 29 February 2016
  • Accepted 9 March 2016
  • Published Online First 24 March 2016


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).

Full article can be obtained via http://jnnp.bmj.com/content/early/2016/03/24/jnnp-2015-312665.extract