Upward Gaze Palsy: a Valuable Sign to Distinguish Spinocerebellar Ataxias

Abstract

Spinocerebellar ataxias (SCAs) represent a large group of heredodegenerative diseases, with great phenotypic and genotypic heterogeneity. However, in the clinical neurological practice, some symptoms and signs might help differentiate the SCAs. This study’s aims were to evaluate the frequency of upward gaze palsy (UGP) and investigate its role in assisting in the clinical differentiation of SCAs. We included 419 patients with SCAs (248 with SCA3, 95 with SCA10, 38 with SCA2, 22 with SCA1, 12 with SCA7, and 4 with SCA6). This study compared UGP with other known markers of disease severity—age of onset, disease duration, SARA score, and size of CAG expansion, and also other semiologic features, as bulging eyes. This sign was significantly more prevalent in SCA3 (64.11%), compared with SCA10 (3.16%; p < 0.001) and other SCAs (SCA1, SCA2, SCA7–11.84%; p < 0.001). UGP showed very high sensibility ins SCA3 (92.9), although lacking of specificity (64.1%). The odds ratio (OR) of UGP were also very high, 23.52 (95% CI 12.38–44.69), and was significantly correlated with larger CAG expansions, age, and disease duration in SCA3 patients, but not with age of onset or severity of the ataxic syndrome. This study showed that UGP is highly suggestive of SCA3 and has high sensitivity for the differential diagnosis among SCAs, and it could be of great value for bedside semiologic tool.

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

Fig. 1

References

  1. 1.

    Marcoglis RL. Dominant spinocerebellar ataxias: a molecular approach to classification, diagnosis, pathogenesis and the future. Expert Rev Mol Diagn. 2003;3(6):715–32. https://doi.org/10.1586/14737159.3.6.715.

    Article  Google Scholar 

  2. 2.

    Durr A. Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol. 2010;9(9):885–94. https://doi.org/10.1016/S1474-4422(10)70183-6.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Teive HAG, Ashizawa T. Primary and secondary ataxias. Curr Opin Neurol. 2015;28(4):413–22. https://doi.org/10.1097/WCO.0000000000000227.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Rossi M, Perez-Lloret S, Doldan L, Cerquetti D, Balej J, Millar Vernetti P, et al. Autosomal dominant cerebellar ataxias: a systematic review of clinical features. Eur J Neurol. 2014;21(4):607–15. https://doi.org/10.1111/ene.12350.

    CAS  Article  Google Scholar 

  5. 5.

    Moscovich M, Okun MS, Favilla C, Figueroa KP, Pulst SM, Perlman S, et al. Clinical evaluation of eye movements in spinocerebellar ataxias. J Neuro-Ophthalmol. 2015;35(1):16–21. https://doi.org/10.1097/WNO.0000000000000167.

    CAS  Article  Google Scholar 

  6. 6.

    Coutinho P Doença de Machado-Joseph: Tentativa de Definição. Tese de Doutoramento 1992. https://repositorio-aberto.up.pt/bitstream/10216/10229/7/644_TD_01_P.pdf. Accessed 15 Jun 2020

  7. 7.

    Schmitz-Hü T, Du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, et al. Scale for the assessment and rating of ataxia development of a new clinical scale. Neurology. 2006;66(11):1717–20. https://doi.org/10.1212/01.wnl.0000219042.60538.92.

    Article  Google Scholar 

  8. 8.

    Braga-Neto P, Godeiro-Junior C, Dutra LA, Pedroso JL, Barsottini OGP. Translation and validation into Brazilian version of the Scale of the Assessment and Rating of Ataxia (SARA). Arq Neuropsiquiatr. 2010;68(2):228–30. https://doi.org/10.1590/S0004-282X2010000200014.

    Article  Google Scholar 

  9. 9.

    Nascimento FA, Garcia BCM, Teive HAG. Teaching video Neuroimages: Upward gaze palsy is a sign of spinocerebellar ataxia type 3. Neurology. 2018;91(5):e-494. https://doi.org/10.1212/WNL.0000000000005913.

    Article  Google Scholar 

  10. 10.

    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. https://doi.org/10.1007/s12311-011-0292-z.

    Article  Google Scholar 

  11. 11.

    Jardim LB, Hauser L, Kieling C, Saute JAM, Xavier R, Rieder CRM, et al. Progression rate of neurological deficits in a 10-year cohort of SCA3 patients. Cerebellum. 2010;9(3):419–28. https://doi.org/10.1007/s12311-010-0179-4.

    Article  Google Scholar 

  12. 12.

    Schmitz-Hübsch T, Coudert M, Bauer P, Giunti P, Globas C, Baliko L, et al. Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms. Neurology. 2008;71(13):982–9. https://doi.org/10.1212/01.wnl.0000325057.33666.72.

    Article  Google Scholar 

  13. 13.

    Jacobi H, Bauer P, Giunti P, Labrum R, Sweeney MG, Charles P, et al. The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study. Neurology. 2011;77(11):1035–41. https://doi.org/10.1212/WNL.0b013e31822e7ca0.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Paulson H. Machado-Joseph disease/spinocerebellar ataxia type 3. Handb Clin Neurol. 2012;103:437–49. https://doi.org/10.1016/B978-0-444-51892-7.00027-9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Jardim LB, Pereira ML, Silveira I, Ferro A, Sequeiros J, Giugliani R. Neurologic findings in Machado-Joseph disease. Arch Neurol. 2001;58(6):899–904. https://doi.org/10.1001/archneur.58.6.899.

    CAS  Article  Google Scholar 

  16. 16.

    Teive H, Munhoz R, Arruda W, Lopes-Cendes I, Raskin S, Werneck L, et al. Spinocerebellar ataxias – genotype-phenotype correlations in 104 Brazilian families. Clinics. 2012;67(5):443–9.

    Article  Google Scholar 

  17. 17.

    Nascimento FA, Rodrigues VOR, Pelloso FC, Camargo CHF, Moro A, Raskin S, et al. Spinocerebellar ataxias in Southern Brazil: genotypic and phenotypic evaluation of 213 families. Clin Neurol Neurosurg. 2019;184:105427. https://doi.org/10.1016/j.clineuro.2019.105427.

    Article  Google Scholar 

  18. 18.

    Domingues BMD, Nascimento FA, Meira AT, Moro A, Raskin S, Ashizawa T, et al. Clinical and genetic evaluation of spinocerebellar ataxia type 10 in 16 Brazilian families. Cerebellum. 2019;18(5):849–54. https://doi.org/10.1007/s12311-019-01064-y.

    Article  Google Scholar 

  19. 19.

    Moro A, Munhoz RP, Arruda WO, Raskin S, Teive HAG. Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias. Arq Neuropsiquiatr. 2013;71(7):428–30. https://doi.org/10.1590/0004-282X20130056.

    Article  Google Scholar 

  20. 20.

    Wu C, Chen DB, Feng L, et al. Oculomotor deficits in spinocerebellar ataxia type 3: potential biomarkers of preclinical detection and disease progression. CNS Neurosci Ther. 2017;23(4):321–8. https://doi.org/10.1111/cns.12676.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Lloyd-Smith SA, Rizzo JR, Rucker JC. Clinical approach to supranuclear brainstem saccadic gaze palsies. Front Neurol. 2017;8:429. https://doi.org/10.3389/fneur.2017.00429.

    Article  Google Scholar 

  22. 22.

    Geiner S, Horn AKE, Wadia NH, Sakai H, Büttner-Ennever JA. The neuroanatomical basis of slow saccades in spinocerebellar ataxia type 2 (Wadia-subtype). Prog Brain Res. 2008;171:575–81. https://doi.org/10.1016/S0079-6123(08)00683-3.

    CAS  Article  Google Scholar 

  23. 23.

    Rüb U, Bürk K, Schöls L, et al. Damage to the reticulotegmental nucleus of the pons in spinocerebellar ataxia type 1, 2, and 3. Neurology. 2004;63(7):1258–63. https://doi.org/10.1212/01.WNL.0000140498.24112.8C.

    Article  Google Scholar 

Download references

Acknowledgments

Professor Márcia Olandowski provided the statistical analysis of the study.

Author information

Affiliations

Authors

Contributions

Research project: conception—Gustavo L. Franklin, Fabio Nascimento, Hélio A. G. Teive; organization—Gustavo L. Franklin, Alex T. Meira, Carlos Henrique F. Camargo, Fabio Nascimento, Hélio A. G. Teive; execution—Gustavo L. Franklin, Alex T. Meira, Carlos Henrique F. Camargo, Fabio Nascimento, Hélio A. G. Teive

Manuscript preparation: writing of the first draft—Gustavo L. Franklin, Fabio Nascimento, Hélio A. G. Teive; review and critique—Gustavo L. Franklin, Alex T. Meira, Carlos Henrique F. Camargo, Fabio Nascimento, Hélio A. G. Teive

Statistics: acquisition of data—Gustavo L. Franklin; analysis—Gustavo L. Franklin, Carlos Henrique F. Camargo; interpretation of data—Gustavo L. Franklin, Alex T. Meira, Carlos Henrique F. Camargo

Corresponding author

Correspondence to Gustavo L. Franklin.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Highlights

The presence of upward gaze palsy (UGP) is statistically higher in SCA3 patients.

UGP is characteristic of SCA3 and of great value to distinguish from others spinocerebellar ataxias

“Coutinho’s sign” should be used to describe the UGP in SCA3 patients.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Franklin, G.L., Meira, A.T., Camargo, C.H.F. et al. Upward Gaze Palsy: a Valuable Sign to Distinguish Spinocerebellar Ataxias. Cerebellum (2020). https://doi.org/10.1007/s12311-020-01154-2

Download citation

Keywords

  • Cerebellar ataxia
  • Ophthalmoplegia
  • Ocular motility disorders
  • Upward gaze palsy