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Combined Cerebellar Proton MR Spectroscopy and DWI Study of Patients with Friedreich’s Ataxia

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Abstract

Friedreich’s ataxia (FRDA) is the commonest autosomal recessive ataxia, caused by GAA triplet expansion in the frataxin gene. Neuropathological studies in FRDA demonstrate that besides the primary neurodegeneration of the dorsal root ganglia, there is a progressive atrophy of the cerebellar dentate nucleus. Diffusion-weighted imaging (DWI) detected microstructural alterations in the cerebellum of FRDA patients. To investigate the biochemical basis of these alterations, we used both DWI and proton MR spectroscopy (1H-MRS) to study the same cerebellar volume of interest (VOI) including the dentate nucleus. DWI and 1H-MRS study of the left cerebellar hemisphere was performed in 28 genetically proven FRDA patients and 35 healthy controls. In FRDA mean diffusivity (MD) values were calculated for the same 1H-MRS VOI. Clinical severity was evaluated using the International Cooperative Ataxia Rating Scale (ICARS). FRDA patients showed a significant reduction of N-acetyl-aspartate (NAA), a neuroaxonal marker, and choline (Cho), a membrane marker, both expressed relatively to creatine (Cr), and increased MD values. In FRDA patients NAA/Cr negatively correlated with MD values (r = −0.396, p = 0.037) and with ICARS score (r = −0.669, p < 0.001). Age-normalized NAA/Cr loss correlated with the GAA expansion (r = −0.492, p = 0.008). The reduced cerebellar NAA/Cr in FRDA suggests that neuroaxonal loss is related to the microstructural changes determining higher MD values. The correlation between NAA/Cr and the severity of disability suggests that this biochemical in vivo MR parameter might be a useful biomarker to evaluate therapeutic interventions.

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Acknowledgments

We thank Dr. Simonetta Righi (Biblioteca Centralizzata Clinica—University of Bologna) for her support in bibliographic research.

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Authors and Affiliations

  1. Functional MR Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy

    Laura Ludovica Gramegna, Caterina Tonon, David Neil Manners, Stefano Zanigni, Claudio Bianchini, Stefania Evangelisti, Claudia Testa & Raffaele Lodi

  2. Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy

    Laura Ludovica Gramegna, Caterina Tonon, David Neil Manners, Stefano Zanigni, Claudio Bianchini, Stefania Evangelisti, Filippo Fortuna, Valerio Carelli, Claudia Testa & Raffaele Lodi

  3. Child Neurology Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, Italy

    Antonella Pini

  4. Neurology Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy

    Rita Rinaldi

  5. Neurology Unit, IRCCS Istitute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy

    Valerio Carelli

Authors
  1. Laura Ludovica Gramegna
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  2. Caterina Tonon
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Corresponding author

Correspondence to Caterina Tonon.

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The S. Orsola-Malpighi Hospital Ethics Committee approved the study, and the written informed consent was obtained from each participant in accordance with the Declaration of Helsinki.

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The authors declare that they have no conflict of interest.

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Gramegna, L.L., Tonon, C., Manners, D.N. et al. Combined Cerebellar Proton MR Spectroscopy and DWI Study of Patients with Friedreich’s Ataxia. Cerebellum 16, 82–88 (2017). https://doi.org/10.1007/s12311-016-0767-z

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  • DOI: https://doi.org/10.1007/s12311-016-0767-z

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