Skip to main content

Advertisement

SpringerLink
Log in

Quality of Life since Pre-Ataxic Phases of Spinocerebellar Ataxia Type 3/Machado–Joseph Disease

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

Abstract

Although health-related quality of life (HRQoL) has been increasingly valued in healthcare and in clinical trials, there is scarce information about it in spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD). This study describes the HRQoL results obtained from ataxic SCA3/MJD subjects, and their non-ataxic offspring included in the BIGPRO (Biomarkers and genetic modifiers in a study of presymptomatic and symptomatic SCA3/MJD carriers) study. Demographic data, clinical scales, and HRQoL instruments EQ-5D-3L and SF-36 were collected. Subjects at 50% risk were genotyped in a double-blind manner. The time left until the onset of the disease was estimated for mutation carriers with a SARA < 3 and combined with disease duration of ataxic subjects (TimeToAfterOnset). Analyses were performed using PASW Statistics version 18.0, R version 4.0.0, and G*Power 3.1, and p < 0.05 was considered statistically significant. Twenty-three ataxic carriers, 33 pre-ataxic carriers, and 21 controls were enrolled. Significant differences between ataxic carriers and controls were seen in EQ-VAS, EQ-5D Index, and in some domains of EQ-5D-3L and SF-36. EQ-5D Index showed the best effect size between ataxic and controls (Cohen’s d = 2.423). Stepwise changes were seen in pre-ataxic subjects, although not statistically significant. TimeToAfterOnset correlated with EQ-5D Index, EQ-VAS, and SF-36 Physical functioning, Role Physical, Pain, and General Health. EQ-5D Index and EQ-VAS correlated with clinical scales in the ataxic group. These results suggest that HRQoL worsens among carriers since pre-ataxic stages and that they might encompass the underlying disease process. In this cohort, SF-36 Physical Functioning, SF-36 General health, and especially EQ-5D Index and EQ-VAS were the best HRQoL instruments to be used as ancillary evidence to support biological and social meanings for future interventions.

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

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Constitution of the World Health Organization. In: World Health Organization. Geneva; 1948.

  2. Karimi M, Brazier J. Health, health-related quality of life, and quality of life: what is the difference? Pharmacoeconomics. 2016;34:645–9. https://doi.org/10.1007/s40273-016-0389-9.

    Article  PubMed  Google Scholar 

  3. Saute JAM, Jardim LB. Machado Joseph disease: clinical and genetic aspects, and current treatment. Expert Opin Orphan Drugs. 2015;3:517–35. https://doi.org/10.1517/21678707.2015.1025747.

    Article  Google Scholar 

  4. de Oliveira CM, Leotti VB, Bolzan G, et al. Pre-ataxic changes of clinical scales and eye movement in Machado-Joseph disease: BIGPRO study. Mov Disord. 2021. https://doi.org/10.1002/mds.28466.

  5. Jacobi H, du Montcel ST, Romanzetti S, et al. Conversion of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 to manifest ataxia (RISCA): a longitudinal cohort study. Lancet Neurol. 2020;19:738–47. https://doi.org/10.1016/S1474-4422(20)30235-0.

    Article  CAS  PubMed  Google Scholar 

  6. du Montcel ST, Charles P, Ribai P, et al. Composite cerebellar functional severity score: validation of a quantitative score of cerebellar impairment. Brain. 2008;131:1352–61. https://doi.org/10.1093/brain/awn059.

    Article  PubMed  Google Scholar 

  7. Schmitz-Hübsch T, Coudert M, Giunti P, et al. Self-rated health status in spinocerebellar ataxia–results from a European multicenter study. Mov Disord. 2010;25:587–95. https://doi.org/10.1002/mds.22740.

    Article  PubMed  Google Scholar 

  8. Schmitz-Hübsch T, Fimmers R, Rakowicz M, et al. Responsiveness of different rating instruments in spinocerebellar ataxia patients. Neurology. 2010;74:678–84. https://doi.org/10.1212/WNL.0b013e3181d1a6c9.

    Article  PubMed  Google Scholar 

  9. Silva RCR, Saute JAM, Silva ACF, et al. Occupational therapy in spinocerebellar ataxia type 3: an open-label trial. Braz J Med Biol Res. 2010;43:537–42. https://doi.org/10.1590/S0100-879X2010005000009.

    Article  CAS  PubMed  Google Scholar 

  10. Jacobi H, Tezenas S, Bauer P, et al. Long-term evolution of patient-reported outcome measures in spinocerebellar ataxias. J Neurol. 2018;265:2040–51. https://doi.org/10.1007/s00415-018-8954-0.

    Article  PubMed  Google Scholar 

  11. Lo RY, Figueroa KP, Pulst SM, et al. Depression and clinical progression in spinocerebellar ataxias. Parkinsonism Relat Disord. 2016;22:87–92. https://doi.org/10.1016/j.parkreldis.2015.11.021.

    Article  PubMed  Google Scholar 

  12. Mastammanavar VS, Kamble N, Yadav R, et al. Non-motor symptoms in patients with autosomal dominant spinocerebellar ataxia. Acta Neurol Scand. 2020;142:368–76. https://doi.org/10.1111/ane.13318.

    Article  PubMed  Google Scholar 

  13. Jacobi H, Reetz K, du Montcel ST, et al. Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: analysis of baseline data. Lancet Neurol. 2013;12:650–8. https://doi.org/10.1016/S1474-4422(13)70104-2.

    Article  PubMed  Google Scholar 

  14. Souza GN, Kersting N, Krum-Santos AC, et al. Spinocerebellar ataxia type 3/Machado–Joseph disease: segregation patterns and factors influencing instability of expanded CAG transmissions. Clin Genet. 2016;90(2):134–40. https://doi.org/10.1111/cge.12719.

    Article  CAS  PubMed  Google Scholar 

  15. Schmitz-Hübsch T, du Montcel ST, Baliko L, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006;66:1717–20. https://doi.org/10.1212/01.wnl.0000219042.60538.92.

    Article  PubMed  Google Scholar 

  16. Kieling C, Rieder CRM, Silva ACF, et al. A neurological examination score for the assessment of spinocerebellar ataxia 3 (SCA3). Eur J Neurol. 2008;15:371–6. https://doi.org/10.1111/j.1468-1331.2008.02078.x.

    Article  CAS  PubMed  Google Scholar 

  17. Trouillas P, Takayanagi T, Hallett M, et al. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci. 1997;145:205–11. https://doi.org/10.1016/s0022-510x(96)00231-6.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  19. Schmitz-Hübsch T, Giunti P, Stephenson DA, et al. SCA Functional Index: a useful compound performance measure for spinocerebellar ataxia. Neurology. 2008;71:486–92. https://doi.org/10.1212/01.wnl.0000324863.76290.19.

    Article  PubMed  Google Scholar 

  20. EuroQol Group. EuroQol–a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199–208. https://doi.org/10.1016/0168-8510(90)90421-9.

    Article  Google Scholar 

  21. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83.

  22. Andrade V, Kind P, Maia AC, et al. Societal preferences for EQ-5D Health States from a Brazilian population survey. 2013;2:2–9. https://doi.org/10.1016/j.vhri.2013.01.009.

  23. Augustovski FA, Irazola VE, Velazquez AP, et al. Argentine valuation of the EQ-5D Health States. Value Health. 2009;12:587–96. https://doi.org/10.1111/j.1524-4733.2008.00468.x.

    Article  PubMed  Google Scholar 

  24. de Mattos EP, Leotti VB, Soong B-W, et al. Age at onset prediction in spinocerebellar ataxia type 3 changes according to population of origin. Eur J Neurol. 2019;26:113–20. https://doi.org/10.1111/ene.13779.

    Article  PubMed  Google Scholar 

  25. de Mol CL, Jansen PR, Muetzel RL, et al. Polygenic multiple sclerosis risk and population-based childhood brain imaging. Ann Neurol. 2020;87:774–87. https://doi.org/10.1002/ana.25717.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ascef B de O, Haddad JPA, Álvares J, et al. Health-related quality of life of patients of Brazilian primary health care. Rev Saúde Pública. 2017;51:22s. https://doi.org/10.11606/S1518-8787.2017051007134.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rezende TJR, de Paiva JLR, Martinez ARM, et al. Structural signature of SCA3: from presymptomatic to late disease stages. Ann Neurol. 2018;84:401–8. https://doi.org/10.1002/ana.25297.

    Article  PubMed  Google Scholar 

  28. 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;23:321–8. https://doi.org/10.1111/cns.12676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. França MCJ, D’Abreu A, Friedman JH, et al. Chronic pain in Machado-Joseph disease: a frequent and disabling symptom. Arch Neurol. 2007;64:1767–70. https://doi.org/10.1001/archneur.64.12.1767.

    Article  PubMed  Google Scholar 

  30. Pedroso JL, França MC, Braga-Neto P, et al. Nonmotor and extracerebellar features in Machado-Joseph disease: a review. Mov Disord. 2013;28:1200–8. https://doi.org/10.1002/mds.25513.

    Article  PubMed  Google Scholar 

  31. Brooks J, Tracey I. From nociception to pain perception: imaging the spinal and supraspinal pathways. J Anat. 2005;207:19–33. https://doi.org/10.1111/j.1469-7580.2005.00428.x.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Velly AM, Mohit S. Epidemiology of pain and relation to psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2018;87:159–67. https://doi.org/10.1016/j.pnpbp.2017.05.012.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the subjects and families who contributed to this study.

Funding

This study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (CAPES-Probral grant number 99999.008137/2015–03), Fundação do Amparo à Pesquisa do Rio Grande do Sul (FAPERGS) (grant numbers 17/2551–0001 035–3 and 17/2551–0001 1463–4), and Fundo de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre (FIPE-HCPA) (grant numbers 17–0014, 17–0015, and 17–0201). G.B. and C.M.O. were supported by CAPES. A.G.R., G.E., and J.A.S. were supported by FAPERGS. A.H.C., L.S.S., A.C.M., M.L.S.P., and L.B.J. were supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil.

Author information

Authors and Affiliations

  1. Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Porto Alegre, 91501-970, Brazil

    Gabriela Bolzan, Lucas Schenatto de Sena, Ana Carolina Martins, Maria-Luiza Saraiva-Pereira & Laura Bannach Jardim

  2. Centros de Pesquisa Clínica e Experimental, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, 90035-903, Brazil

    Gabriela Bolzan, Camila Maria de Oliveira, Nathalia Kersting, Mariana Rieck, Lucas Schenatto de Sena, Ana Carolina Martins, Maria-Luiza Saraiva-Pereira & Laura Bannach Jardim

  3. Departamento de Estatística, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Porto Alegre, 91501-970, Brazil

    Vanessa Bielefeldt Leotti

  4. Programa de Pós-Graduação em Epidemiologia, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Porto Alegre, 91501-970, Brazil

    Vanessa Bielefeldt Leotti

  5. Programa de Pós-Graduação em Ciências Médicas, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2400, Porto Alegre, 90.035-002, Brazil

    Camila Maria de Oliveira & Laura Bannach Jardim

  6. Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2400, Porto Alegre, 90.035-002, Brazil

    Gabriela Ecco, Amanda Henz Cappelli, Anastacia Guimarães Rocha & Laura Bannach Jardim

  7. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, 90035-903, Brazil

    Maria-Luiza Saraiva-Pereira & Laura Bannach Jardim

  8. Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, Porto Alegre, 90035-003, Brazil

    Maria-Luiza Saraiva-Pereira

  9. Departamento de Medicina Interna, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2400, Porto Alegre, 90.035-002, Brazil

    Laura Bannach Jardim

Authors
  1. Gabriela Bolzan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vanessa Bielefeldt Leotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Camila Maria de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriela Ecco
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amanda Henz Cappelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anastacia Guimarães Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nathalia Kersting
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mariana Rieck
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lucas Schenatto de Sena
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ana Carolina Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Maria-Luiza Saraiva-Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Laura Bannach Jardim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

G.B., V.B.L., and L.B.J. contributed to the conception and design of the study; G.B., V.B.L., C.M.O., A.H.C., A.G.R., G.E., J.A.S., N.K., M.R., A.C.M., L.S.S., M.L.S.P., and L.B.J. contributed to the acquisition and analysis of data; G.B., V.B.L., M.L.S.P., and L.B.J. contributed to drafting the text and preparing the figures. All authors reviewed the manuscript.

Corresponding author

Correspondence to Laura Bannach Jardim.

Ethics declarations

Conflicts of Interest

The authors declare no competing interests.

Ethics Approval

This study was approved by the Institutional Ethics Committee (Comissão de Ética em Pesquisa do Hospital de Clínicas de Porto Alegre) and by the Brazilian Board (Comissão Nacional de Pesquisa, CONEP) by the number CAAE 60751916.3.0000.5327. The present protocol was registered at the Clinical Trials under the number NCT04419974.

Consent to Participate

Written informed consent was obtained from all study participants.

Additional information

Publisher’s Note

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

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bolzan, G., Leotti, V.B., de Oliveira, C.M. et al. Quality of Life since Pre-Ataxic Phases of Spinocerebellar Ataxia Type 3/Machado–Joseph Disease. Cerebellum 21, 297–305 (2022). https://doi.org/10.1007/s12311-021-01299-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-021-01299-8

Keywords

Search

Navigation