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Superior Cerebellar Peduncle Atrophy in Friedreich’s Ataxia Correlates with Disease Symptoms

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Abstract

Friedreich’s ataxia (FRDA) is the most common early onset inherited ataxia with clinical manifestations, including gradual progression of unremitting cerebellar–sensory ataxia, peripheral sensory loss, loss of lower limb tendon reflexes and hypertrophic cardiomyopathy. Although atrophy of the superior cerebellar peduncle (SCP) has been reported in several magnetic resonance imaging (MRI) studies of FRDA, the relationship of SCP changes to genetic and clinical features of FRDA has not been investigated. We acquired T1-weighted MRI scans in 12 right-handed individuals with FRDA, homozygous for a GAA expansion in intron 1 of FXN, as well as 13 healthy age-matched controls. The corrected cross-sectional areas of the right (left) SCP in the individuals with FRDA (R, 20 ± 7.9 mm2; L, 25 ± 5.6 mm2) were significantly smaller than for controls (R, 68 ± 16 mm2; L, 78 ± 17 mm2) (p < 0.001). The SCP volumes of individuals with FRDA were negatively correlated with Friedreich’s ataxia rating scale score (r = −0.553) and disease duration (r = −0.541), and positively correlated with the age of onset (r = 0.548) (p < 0.05). These findings suggest that structural MR imaging of the SCP can provide a surrogate marker of disease severity in FRDA and support the potential role of structural MRI as a biomarker in the evaluation of neurodegenerative diseases and therapies.

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Acknowledgments

We thank the participants for taking part in this study. This study was supported by funding from the Friedreich Ataxia Research Association (Australasia), Friedreich Ataxia Research Alliance (USA) and Murdoch Childrens Research Institute. HA received a Melbourne International fee remission scholarship and a Melbourne International Research scholarship. MBD is an NHMRC practitioner fellow. GFE is an NHMRC research fellow.

Conflict of Interest

Dr. Hamed Akhlaghi received a Melbourne International Fee Remission Scholarship and a Melbourne International Research Scholarship.

Professor Elsdon Storey has received honoraria (payable to his institution) from Pfizer for lecturing on non-drug-related issues at an education course. He is a co-investigator on an NIH trial for which Merck is providing active drug (aspirin and placebo).

Professor Martin B. Delatycki is associate editor for BMC Neurology; he receives grants from NHMRC, Friedreich Ataxia Research Alliance, Friedreich Ataxia Research Association, and he is on the Pfizer Australia Neuroscience Grant Panel.

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Authors and Affiliations

  1. Florey Neurosciences Institute, Centre for Neurosciences, University of Melbourne, Parkville, VIC, Australia

    Hamed Akhlaghi & Gary F. Egan

  2. Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, VIC, Australia

    Louise Corben & Martin B. Delatycki

  3. Experimental Neuropsychology Research Unit, School of Psychology and Psychiatry, Monash University, Clayton, VIC, Australia

    Louise Corben, Nellie Georgiou-Karistianis & John Bradshaw

  4. Department of Medicine (Neurosciences), Monash University (Alfred Hospital Campus), Prahran, VIC, Australia

    Elsdon Storey

  5. Department of Clinical Genetics, Austin Health, Heidelberg, VIC, Australia

    Martin B. Delatycki

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  1. Hamed Akhlaghi
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Correspondence to Hamed Akhlaghi.

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Akhlaghi, H., Corben, L., Georgiou-Karistianis, N. et al. Superior Cerebellar Peduncle Atrophy in Friedreich’s Ataxia Correlates with Disease Symptoms. Cerebellum 10, 81–87 (2011). https://doi.org/10.1007/s12311-010-0232-3

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  • DOI: https://doi.org/10.1007/s12311-010-0232-3

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