Skip to main content

Advertisement

SpringerLink
Log in

Spinal Cord Atrophy Correlates with Disability in Friedreich’s Ataxia

  • Original Paper
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Although Friedreich’s ataxia is characterized by spinal cord atrophy, it remains to be investigated the possible correlation of such atrophy with clinical disability and genetic parameters. Thirty-three patients with Friedreich’s ataxia and 30 healthy controls underwent MRI on a 3 T scanner. We used T1-weighted 3D images to estimate spinal cord area and eccentricity at C2/C3 level based on a semi-automatic image segmentation protocol. We quantified severity of ataxia with the Friedreich ataxia rating scale (FARS). Mean cord area in Friedreich’s ataxia was smaller than in controls (38 vs 67.9 mm2, p < 0.001). In contrast, mean cord eccentricity was significantly higher in Friedreich’s ataxia when compared to the controls (0.82 vs 0.76, p < 0.001). There was a significant correlation between cord areas and the FARS scores (r = −0.53, p = 0.002). Cord damage in Friedreich’s ataxia results in atrophy combined with flattening. Cord area is associated to clinical disability and might be useful as a biomarker in the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Campuzano V, Montermini L, Moltò MD, Pianese L, Cossée M, Cavalcanti F, et al. Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science. 1996;271:1423–7.

    Article  PubMed  CAS  Google Scholar 

  2. Pandolfo M. Friedreich Ataxia. Arch Neurol. 2008;65:1296–303.

    Article  PubMed  Google Scholar 

  3. Koeppen AH. Friedreich’s ataxia: pathology, pathogenesis, and molecular genetics. J Neurol Sci. 2011;303:1–12.

    Article  PubMed  CAS  Google Scholar 

  4. Morral JA, Davis AN, Qian J, Gelman BB, Koeppen AH. Pathology and pathogenesis of sensory neuropathy in Friedreich’s ataxia. Acta Neuropathol. 2010;120:97–108.

    Article  PubMed  Google Scholar 

  5. De Michele G, Di Salle F, Filla A, D’Alessio G, Ambrosio G, Viscardi L, et al. Magnetic resonance imaging in “typical” and “late onset” Friedreich’s disease and early onset cerebellar ataxia with retained tendon reflexes. Ital J Neurol Sci. 1995;16:303–8.

    Article  PubMed  Google Scholar 

  6. Wessel K, Schroth G, Diener HC, Müller-Forell W, Dichgans J. Significance of MRI-confirmed atrophy of the cranial spinal cord in Friedreich’s ataxia. Eur Arch Psychiatry Neurol Sci. 1989;238:225–30.

    Article  PubMed  CAS  Google Scholar 

  7. Klockgether T, Petersen D, Grodd W, Dichgans J. Early onset cerebellar ataxia with retained tendon reflexes. Clinical, electrophysiological and MRI observations in comparison with Friedreich’s ataxia. Brain. 1991;114:1559–73.

    Article  PubMed  Google Scholar 

  8. Mascalchi M, Salvi F, Piacentini S, Bartolozzi C. Friedreich’s ataxia: MR findings involving the cervical portion of the spinal cord. AJR Am J Roentgenol. 1994;163:187–91.

    PubMed  CAS  Google Scholar 

  9. Bonati U, Fisniku LK, Altmann DR, Yiannakas MC, Furby J, Thompson AJ, et al. Cervical cord and brain grey matter atrophy independently associate with long-term MS disability. J Neurol Neurosurg Psychiatry. 2011;82:471–2.

    Article  PubMed  CAS  Google Scholar 

  10. Bakshi R, Dandamudi VS, Neema M, De C, Bermel RA. Measurement of brain and spinal cord atrophy by magnetic resonance imaging as a tool to monitor multiple sclerosis. J Neuroimaging. 2005;15(4 Suppl):30S–45S.

    Article  PubMed  Google Scholar 

  11. Lukas C, Hahn HK, Bellenberg B, Hellwig K, Globas C, Schimrigk SK, et al. Spinal cord atrophy in spinocerebellar ataxia type 3 and 6: impact on clinical disability. J Neurol. 2008;255:1244–9.

    Article  PubMed  Google Scholar 

  12. França Jr MC, D’Abreu A, Zanardi VA, Faria AV, Nucci A, Lopes-Cendes I, et al. MRI shows dorsal lesions and spinal cord atrophy in chronic sensory neuronopathies. J Neuroimaging. 2008;18:168–72.

    Article  PubMed  Google Scholar 

  13. Filla A, De Michele G, Cavalcanti F, Pianese L, Monticelli A, Campanella G, Cocozza S. The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. Am J Hum Genet. 1996;59:554–60.

    PubMed  CAS  Google Scholar 

  14. Subramony SH, May W, Lynch D, Gomez C, Fischbeck K, Hallett M, et al. Measuring Friedreich ataxia: interrater reliability of a neurologic rating scale. Neurology. 2005;64:1261–2.

    Article  PubMed  CAS  Google Scholar 

  15. Bergo FPG (2011) SpineSeg—Semi-Automatic Spinal Cord Segmentation—Usage Guide. http://www.liv.ic.unicamp.br/∼bergo/spineseg/; access date: 12 February 2012.

  16. Bergo FPG, Falcão AX, Miranda PAV, et al. Automatic image segmentation by tree pruning. J Math Imaging Vis. 2007;29:141–62.

    Article  Google Scholar 

  17. Fitzgibbon A, Pilu M, Fisher RB. Direct least square fitting of ellipses. IEEE Trans Patt Anal Mach Intel. 1999;21:476–80.

    Article  Google Scholar 

  18. Lamarche JB, Lemieux B, Lieu HB. The neuropathology of “typical” Friedreich’s ataxia in Quebec. Can J Neurol Sci. 1984;11(4 Suppl):592–600.

    PubMed  CAS  Google Scholar 

  19. Chevis CF, França Jr MC, Bergo FPG, D’Abreu A, Guimarães RP, Lopes-Cendes I, et al. Distinct patterns of spinal cord atrophy in Machado-Joseph Disease and Friedreich’s ataxia. Neurology. 2011;76:A413.

    Google Scholar 

  20. Rüb U, Brunt ER, Deller T. New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado–Joseph disease). Curr Opin Neurol. 2008;21:111–6.

    Article  PubMed  Google Scholar 

  21. Rizzo G, Tonon C, Valentino ML, Manners D, Fortuna F, Gellera C, et al. Brain diffusion-weighted imaging in Friedreich’s ataxia. Mov Disord. 2011;26:705–12.

    Article  PubMed  Google Scholar 

  22. Akhlaghi H, Corben L, Georgiou-Karistianis N, Bradshaw J, Storey E, Delatycki MB, et al. Superior cerebellar peduncle atrophy in Friedreich’s ataxia correlates with disease symptoms. Cerebellum. 2011;10:81–7.

    Article  PubMed  Google Scholar 

  23. Pagani E, Ginestroni A, Della Nave R, Agosta F, Salvi F, De Michele G, et al. Assessment of brain white matter fiber bundle atrophy in patients with Friedreich ataxia. Radiology. 2010;255:882–9.

    Article  PubMed  Google Scholar 

  24. Della Nave R, Ginestroni A, Tessa C, Salvatore E, Bartolomei I, Salvi F, et al. Brain white matter tracts degeneration in Friedreich ataxia. An in vivo MRI study using tract-based spatial statistics and voxel-based morphometry. Neuroimage. 2008;40:19–25.

    Article  PubMed  Google Scholar 

  25. Fahey MC, Corben L, Collins V, Churchyard AJ, Delatycki MB. How is disease progress in Friedreich’s ataxia best measured? A study of four rating scales. J Neurol Neurosurg Psychiatry. 2007;78:411–3.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).

Conflict of Interest

The authors report no conflict of interests regarding this research. This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).

Author information

Authors and Affiliations

  1. Department of Neurology and Neuroimaging Laboratory, Faculty of Medicine, University of Campinas—UNICAMP, Rua Tessália Vieira de Camargo, 126. Cidade Universitaria “Zeferino Vaz”, Campinas, São Paulo, Brazil, 13083-887

    Camila F. Chevis, Cynthia B. da Silva, Anelyssa D’Abreu, Fernando Cendes, Felipe P. G. Bergo & Marcondes C. França Jr

  2. Department of Medical Genetics, Faculty of Medicine, University of Campinas—UNICAMP, Campinas, São Paulo, Brazil

    Iscia Lopes-Cendes

Authors
  1. Camila F. Chevis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cynthia B. da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anelyssa D’Abreu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Iscia Lopes-Cendes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fernando Cendes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Felipe P. G. Bergo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marcondes C. França Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcondes C. França Jr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chevis, C.F., da Silva, C.B., D’Abreu, A. et al. Spinal Cord Atrophy Correlates with Disability in Friedreich’s Ataxia. Cerebellum 12, 43–47 (2013). https://doi.org/10.1007/s12311-012-0390-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-012-0390-6

Keywords

Search

Navigation