Projects per year
Background: Friedreich ataxia is a recessively inherited, progressive neurological disease characterized by impaired mitochondrial iron metabolism. The dentate nuclei of the cerebellum are characteristic sites of neurodegeneration in the disease, but little is known of the longitudinal progression of abnormalities in these structures. Methods: Using in vivo magnetic resonance imaging, including quantitative susceptibility mapping, we investigated changes in iron concentration and volume in the dentate nuclei in individuals with Friedreich ataxia (n = 20) and healthy controls (n = 18) over a 2-year period. Results: The longitudinal rate of iron concentration was significantly elevated bilaterally in participants with Friedreich ataxia relative to healthy controls. Atrophy rates did not differ significantly between groups. Change in iron concentration and atrophy both correlated with baseline disease severity or duration, indicating sensitivity of these measures to disease stage. Specifically, atrophy was maximal in individuals early in the disease course, whereas the rate of iron concentration increased with disease progression. Conclusions: Progressive dentate nucleus abnormalities are evident in vivo in Friedreich ataxia, and the rates of change of iron concentration and atrophy in these structures are sensitive to the disease stage. The findings are consistent with an increased rate of iron concentration and atrophy early in the disease, followed by iron accumulation and stable volume in later stages. This pattern suggests that iron dysregulation persists after loss of the vulnerable neurons in the dentate. The significant changes observed over a 2-year period highlight the utility of quantitative susceptibility mapping as a longitudinal biomarker and staging tool.
- dentate nucleus
- Friedreich ataxia
- quantitative susceptibility mapping
- 3 Finished
Egan, G., Rosa, M., Lowery, A., Stuart, G., Arabzadeh, E., Skafidas, E., Ibbotson, M., Petrou, S., Paxinos, G., Mattingley, J., Garrido, M., Sah, P., Robinson, P. A., Martin, P., Grunert, U., Tanaka, K., Mitra, P., Johnson, G., Diamond, M., Margrie, T., Leopold, D., Movshon, J., Markram, H., Victor, J., Hill, S. & Jirsa, V.
Australian National University , ETH Zurich, Australian Research Council (ARC), Karolinska Institute, QIMR Berghofer Medical Research Institute, Ecole Polytechnique Federale de Lausanne (Swiss Federal Institute of Technology in Lausanne) , Monash University, University of Melbourne, University of New South Wales, University of Queensland , University of Sydney, Monash University – Internal University Contribution, National Institutes of Health (United States), Cornell University, New York University, MRC National Institute for Medical Research, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Duke University, Cold Spring Harbor Laboratory, RIKEN
25/06/14 → 31/12/21
A longitudinal neuroimaging study investigating reorganisation of cerebellar-cerebral networks in Friedreich ataxia
1/01/13 → 31/12/16