The Cerebellum

, Volume 16, Issue 4, pp 792–796 | Cite as

Spinal Cord Damage in Spinocerebellar Ataxia Type 1

  • Carlos Roberto MartinsJr
  • Alberto Rolim Muro Martinez
  • Thiago Junqueira Ribeiro de Rezende
  • Lucas Melo Teixeira Branco
  • José Luiz Pedroso
  • Orlando G. P. Barsottini
  • Iscia Lopes-Cendes
  • Marcondes C. FrançaJrEmail author
Original Paper


Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder caused by a CAG repeat expansion, characterized by progressive cerebellar ataxia and pyramidal signs. Non-motor and extracerebellar symptoms may occur. MRI-based studies in SCA1 focused in the cerebellum and connections, but there are no data about cord damage in the disease and its clinical relevance. To evaluate in vivo spinal cord damage in SCA1, a group of 31 patients with SCA1 and 31 age- and gender-matched healthy controls underwent MRI on a 3T scanner. We used T1-weighted 3D images to estimate the cervical spinal cord area (CA) and eccentricity (CE) at three C2/C3 levels based on a semi-automatic image segmentation protocol. The scale for assessment and rating of ataxia (SARA) was used to quantify disease severity. The groups were significantly different regarding CA (47.26 ± 7.4 vs. 68.8 ± 5.7 mm2, p < 0.001) and CE values (0.803 ± 0.044 vs. 0.774 ± 0.043, p < 0.05). Furthermore, in the patient group, CA presented significant correlation with SARA scores (R = −0.633, p < 0.001) and CAGn expansion (R = −0.658, p < 0.001). CE was not associated with SARA scores (p = 0.431). In the multiple variable regression, CA was strongly associated with disease duration (coefficient −0.360, p < 0.05) and CAGn expansion (coefficient −1.124, p < 0.001). SCA1 is characterized by cervical cord atrophy and anteroposterior flattening. Morphometric analyses of the spinal cord MRI might be a useful biomarker in the disease.


Spinal cord MRI Ataxia Spinocerebellar ataxia type 1 Polyglutamine disorders Biomarker 


Compliance with Ethical Standards

Conflicts 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)—grant 2013/01766-7.


  1. 1.
    Bürk K, Abele M, Fetter M, Dichgans J, Skalej M, Laccone F, et al. Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3. Brain. 1996;119(Pt 5):1497–505.CrossRefPubMedGoogle Scholar
  2. 2.
    Bürk K, Fetter M, Abele M, Laccone F, Brice A, Dichgans J, et al. Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3. J Neurol. 1999;246:789–97.CrossRefPubMedGoogle Scholar
  3. 3.
    Schöls L, Bauer P, Schmidt T, Schulte T, Riess O. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004;3:291–304.CrossRefPubMedGoogle Scholar
  4. 4.
    Banfi S, Servadio A, Chung MY, Kwiatkowski Jr TJ, McCall AE, Duvick LA, et al. Identification and characterization of the gene causing type 1 spinocerebellar ataxia. Nat Genet. 1994;7:513–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Chong SS, McCall AE, Cota J, Subramony SH, Orr HT, Hughes MR, et al. Genetic and somatic tissue-specific heterogeneity of the expanded SCA1 CAG repeat in spinocerebellar ataxia type 1. Nat Genet. 1995;10:344–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Robitaille Y, Lopes-Cendes I, Becher M, Rouleau G, Clark AW, et al. The neuropathology of the CAG repeat diseases: review and update of genetic and molecular features. Brain Pathol. 1997;7:901–26.CrossRefPubMedGoogle Scholar
  7. 7.
    Iwabuchi K, Tsuchiya K, Uchihara T, Yagishita S. Autosomal dominant spinocerebellar degenerations. Clinical, pathological and genetic correlations. Rev Neurol (Paris). 1999;155:255–70.Google Scholar
  8. 8.
    Pedroso JL, Barsottini OG. Spinal cord atrophy in spinocerebellar ataxia type 1. Arq Neuropsiquiatr. 2013;71(12):977.CrossRefPubMedGoogle Scholar
  9. 9.
    Pedroso JL, de Souza PV, Pinto WB, Braga-Neto P, Albuquerque MV, Saraiva-Pereira ML, et al. SCA1 patients may present as hereditary spastic paraplegia and must be included in spastic-ataxias group. Parkinsonism Relat Disord. 2015;21(10):1243–6.CrossRefPubMedGoogle Scholar
  10. 10.
    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(8):1244–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Chevis CF, da Silva CB, D’Abreu A, Lopes-Cendes I, Cendes F, França Jr MC, et al. Spinal cord atrophy correlates with disability in Friedreich’s ataxia. Cerebellum. 2013;12:43–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Branco LM, De Albuquerque M, De Andrade HM, Bergo FP, Nucci A, França Jr MC. Spinal cord atrophy correlates with disease duration and severity in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:93–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Fahl CN, Branco LM, Bergo FP, D'Abreu A, Lopes-Cendes I, França Jr MC. Spinal cord damage in Machado-Joseph disease. Cerebellum. 2015;14(2):128–32.CrossRefPubMedGoogle Scholar
  14. 14.
    Braga-Neto P, Godeiro-Junior C, Dutra LA, Pedroso JL, Barsottini OG. Translation and validation into Brazilian version of the Scale of the Assessment and Rating of Ataxia (SARA). Arq Neuropsiquiatr. 2010;68:228–30.CrossRefPubMedGoogle Scholar
  15. 15.
    Bergo FPG, França MC Jr., Chevis CF, Cendes F. SpineSeg: a segmentation and measurement tool for evaluation of spinal cord atrophy. In: CISTI’2012 (7ª Conferencia Ibérica de Sistemas y Tecnologia de Información); Madrid, Spain. IEEE. 2012;400–403.Google Scholar
  16. 16.
    Klockgether T, Lüdtke R, Kramer B, Abele M, Bürk K, Schöls L, et al. The natural history of degenerative ataxia: a retrospective study in 466 patients. Brain. 1998;121:589–600.CrossRefPubMedGoogle Scholar
  17. 17.
    Wüllner U, Reimold M, Abele M, Bürk K, Minnerop M, Dohmen BM, et al. Dopamine transporter positron emission tomography in spinocerebellar ataxia type 1, 2, 3, and 6. Arch Neurol. 2005;62:1280–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Yokota T, Sasaki H, Iwabuchi K, Shiojiri T, Yoshino A, Otagiri A, et al. Electrophysiological features of central motor conduction in spinocerebellar atrophy type 1, type 2, and Machado-Joseph disease. J Neurol Neurosurg Psychiatry. 1998;65(4):530–4.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Liang L, Chen T, Wu Y. The electrophysiology of spinocerebellar ataxias. Neurophysiol Clin. 2016;46(1):27–34.CrossRefPubMedGoogle Scholar
  20. 20.
    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.CrossRefPubMedGoogle Scholar
  21. 21.
    Jacobi H, Hauser TK, Giunti P, Globas C, Bauer P, Schmitz-Hübsch T, et al. Spinocerebellar ataxia types 1, 2, 3 and 6: the clinical spectrum of ataxia and morphometric brainstem and cerebellar findings. Cerebellum. 2012;11(1):155–66.CrossRefPubMedGoogle Scholar
  22. 22.
    Matilla-Dueñas A, Goold R, Giunti P. Clinical, genetic, molecular, and pathophysiological insights into spinocerebellar ataxia type 1. Cerebellum. 2008;7(2):106–14.CrossRefPubMedGoogle Scholar
  23. 23.
    Rezende TJ, de Albuquerque M, Lamas GM, Martinez AR, Campos BM, Casseb RF, et al. Multimodal MRI-based study in patients with SPG4 mutations. PLoS One. 2015;10(2):e0117666.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Carlos Roberto MartinsJr
    • 1
  • Alberto Rolim Muro Martinez
    • 1
  • Thiago Junqueira Ribeiro de Rezende
    • 1
  • Lucas Melo Teixeira Branco
    • 1
  • José Luiz Pedroso
    • 2
  • Orlando G. P. Barsottini
    • 2
  • Iscia Lopes-Cendes
    • 3
  • Marcondes C. FrançaJr
    • 1
    • 4
    Email author
  1. 1.Department of Neurology and Neuroimaging Laboratory, School of Medical SciencesUniversity of Campinas—UNICAMPCampinasBrazil
  2. 2.Department of Neurology, Ataxia UnitFederal University of São Paulo—UNIFESPSão PauloBrazil
  3. 3.Department of Medical Genetics, School of Medical SciencesUniversity of Campinas—UNICAMPCampinasBrazil
  4. 4.Department of NeurologyUniversity of Campinas—UNICAMPCampinasBrazil

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