Skip to main content

Spinal Cord Damage in Spinocerebellar Ataxia Type 1

Abstract

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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    CAS  Google Scholar 

  8. 8.

    Pedroso JL, Barsottini OG. Spinal cord atrophy in spinocerebellar ataxia type 1. Arq Neuropsiquiatr. 2013;71(12):977.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    Article  PubMed  Google 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.

  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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Liang L, Chen T, Wu Y. The electrophysiology of spinocerebellar ataxias. Neurophysiol Clin. 2016;46(1):27–34.

    Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Marcondes C. França Jr.

Ethics declarations

Conflicts of Interest

The authors report no conflict of interests regarding this research.

Funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)—grant 2013/01766-7.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Martins, C.R., Martinez, A.R.M., de Rezende, T.J.R. et al. Spinal Cord Damage in Spinocerebellar Ataxia Type 1. Cerebellum 16, 792–796 (2017). https://doi.org/10.1007/s12311-017-0854-9

Download citation

Keywords

  • Spinal cord
  • MRI
  • Ataxia
  • Spinocerebellar ataxia type 1
  • Polyglutamine disorders
  • Biomarker