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NESSCA Validation and Responsiveness of Several Rating Scales in Spinocerebellar Ataxia Type 2

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Abstract

Spinocerebellar ataxia type 2 (SCA2), caused by a CAG expansion (CAGexp) at ATXN2, has a complex clinical picture. While validated ataxia scales are available, comprehensive instruments to measure all SCA2 neurological manifestations are required. This study aims to validate the Neurological Examination Score for the assessment of Spinocerebellar Ataxias (NESSCA) to be used in SCA2 and to compare its responsiveness to those obtained with other instruments. NESSCA, SARA, SCAFI, and CCFS scales were applied in symptomatic SCA2 patients. Correlations were done with age at onset, disease duration, CAGexp, and between scales. Responsiveness was estimated by comparing deltas of stable to worse patients after 12 months, according to Patient Global Impression of change, and the area under the curve (AUC) of the Receiver Operating Characteristics curve of scores range. Eighty-eight evaluations (49 patients) were obtained. NESSCA had an even distribution and correlated with disease duration (r = 0.55), SARA (r = 0.63), and CAGexp (rho = 0.32): both explained 44% of NESSCA variance. Deltas (95% CI) after 1 year in stable and worse patients were only significantly different for SARA. NESSCA, SARA, SCAFI, and CCFS AUC were 0.63, 0.81, 0.49, and 0.48, respectively. NESSCA is valid to be used in SCA2. However, the only instrument that presented good responsiveness to change in 1 year was SARA. We suggest that NESSCA can be used as a secondary outcome in future trials in SCA2 due to the burden of neurological disabilities related to disease progression.

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References

  1. Velázquez-Pérez L, Rodríguez-Labrada R, García-Rodríguez JC, Almaguer-Mederos LE, Cruz-Mariño T, Laffita-Mesa JM. A comprehensive review of spinocerebellar ataxia type 2 in Cuba. Cerebellum. 2011;10(2):184–98.

    Article  PubMed  Google Scholar 

  2. Pulst SM. Spinocerebellar Ataxia Type 2. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle: University of Washington, Seattle; 1993–2016. 1998.

  3. Auburger GWJ. Spinocerebellar ataxia type 2. In: Subramony SH, Dürr A, editors. Handbook of clinical neurology: ataxic disorders. Edinburgh: Elsevier; 2012. p. 423–36.

    Google Scholar 

  4. Sequeiros J, Martins S, Silveira I. Epidemiology and population genetics of degenerative ataxias. Handb Clin Neurol. 2012;103:227–51.

    Article  PubMed  Google Scholar 

  5. de Castilhos RM, Furtado GV, Gheno TC, Schaeffer P, Russo A, Barsottini O, Pedroso JL, Salarini DZ, Vargas FR, de Lima MA, Godeiro C, Santana-da-Silva LC, Toralles MB, Santos S, van der Linden Jr H, Wanderley HY, de Medeiros PF, Pereira ET, Ribeiro E, Saraiva-Pereira ML, Jardim LB, Rede Neurogenetica. Spinocerebellar ataxias in Brazil—frequencies and modulating effects of related genes. Cerebellum. 2014;13(1):17–28.

    Article  CAS  PubMed  Google Scholar 

  6. Schmitz-Hübsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, Giunti P, Globas C, Infante J, Kang JS, Kremer B, Mariotti C, Melegh B, Pandolfo M, Rakowicz M, Ribai P, Rola R, Schöls L, Szymanski S, van de Warrenburg BP, Dürr A, Klockgether T, Fancellu R. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006;66(11):1717–20.

    Article  PubMed  Google Scholar 

  7. Schmitz-Hübsch T, Giunti P, Stephenson DA, Globas C, Baliko L, Saccà F, Mariotti C, Rakowicz M, Szymanski S, Infante J, van de Warrenburg BP, Timmann D, Fancellu R, Rola R, Depondt C, Schöls L, Zdzienicka E, Kang JS, Döhlinger S, Kremer B, Melegh B, Filla A, Klockgether T. SCA functional index: a useful compound performance measure for spinocerebellar ataxia. Neurology. 2008a;71(7):486–92.

    Article  PubMed  Google Scholar 

  8. du Montcel ST, Charles P, Ribai P, Goizet C, Le Bayon A, Labauge P, Guyant-Maréchal L, Forlani S, Jauffret C, Vandenberghe N, N’guyen K, Le Ber I, Devos D, Vincitorio CM, Manto MU, Tison F, Hannequin D, Ruberg M, Brice A, Durr A. Composite cerebellar functional severity score: validation of a quantitative score of cerebellar impairment. Brain. 2008;131(Pt 5):1352–61.

    Article  PubMed  Google Scholar 

  9. Schmitz-Hübsch T, Coudert M, Bauer P, Giunti P, Globas C, Baliko L, Filla A, Mariotti C, Rakowicz M, Charles P, Ribai P, Szymanski S, Infante J, van de Warrenburg BP, Dürr A, Timmann D, Boesch S, Fancellu R, Rola R, Depondt C, Schöls L, Zdienicka E, Kang JS, Döhlinger S, Kremer B, Stephenson DA, Melegh B, Pandolfo M, di Donato S, du Montcel ST, Klockgether T. Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms. Neurology. 2008;71(13):982–9.

    Article  PubMed  Google Scholar 

  10. Kieling C, Rieder CR, Silva AC, Saute JA, Cecchin CR, Monte TL, Jardim LB. A neurological examination score for the assessment of spinocerebellar ataxia 3 (SCA3). Eur J Neurol. 2008;15(4):371–6.

    Article  CAS  PubMed  Google Scholar 

  11. Furr RM, Bacharach VR. Psychometrics: an introduction. Los Angeles: Sage Publications; 2008.

    Google Scholar 

  12. Streiner DL, Norman GR. Health Measurement scales, a practical guide to their development and use. 4th ed. Oxford: Oxford University Press; 2008. p. 247–74.

    Book  Google Scholar 

  13. Rüb U, Schöls L, Paulson H, Auburger G, Kermer P, Jen JC, Seidel K, Korf HW, Deller T. Clinical features, neurogenetics and neuropathology of the polyglutamine spinocerebellar ataxias type 1, 2, 3, 6 and 7. Prog Neurobiol. 2013;104:38–66.

    Article  PubMed  Google Scholar 

  14. Bürk K, Abele M, Fetter M, Dichgans J, Skalej M, Laccone F, Didierjean O, Brice A, Klockgether T. Autosomal dominant cerebellar ataxia type I. Clinical features and MRI in families with SCA1, SCA2 and SCA3. Brain. 1996;119:1497–505.

    Article  PubMed  Google Scholar 

  15. Bürk K, Globas C, Bosch S, Gräber S, Abele M, Brice A, Dichgans J, Daum I, Klockgether T. Cognitive deficits in spinocerebellar ataxia 2. Brain. 1999;122:769–77.

    Article  PubMed  Google Scholar 

  16. Cancel G, Dürr A, Didierjean O, Imbert G, Bürk K, Lezin A, Belal S, Benomar A, Abada-Bendib M, Vial C, Guimaraes J, Chneiweiss A, Stevanin G, Yvert G, Abbas N, Saudou F, Lebre AS, Yahyaoui M, Hentati F, Vernant JC, Klockgether T, Mandel JL, Agid Y, Brice A. Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families. Hum Mol Genet. 1997;6:709–15.

    Article  CAS  PubMed  Google Scholar 

  17. Charles P, Camuzat A, Benammar N, Sellal F, Destee A, Bonnet AM, Lesage S, Le Ber I, Stevanin G, Durr A, Brice A, French Parkinson’s Disease Genetic Study Group. Are interrupted SCA2 CAG repeat expansions responsible for parkinsonism? Neurology. 2007;69:1970–5.

    Article  CAS  PubMed  Google Scholar 

  18. Jacobi H, Bauer P, Giunti P, et al. The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study. Neurology. 2011;77:1035–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Klockgether T, Ludtke R, Kramer B, Abele M, Burk K, Schols L, Riess O, Laccone F, Boesch S, Lopes-Cendes I, Brice A, Inzelberg R, Zilber N, Dichgans J. The natural history of degenerative ataxia: a retrospective study in 466 patients. Brain. 1998;121:589–600.

    Article  PubMed  Google Scholar 

  20. Schols L, Amoiridis G, Büttner T, Przuntek H, Epplen JT, Riess O. Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? Ann Neurol. 1997;42:924–32.

    Article  CAS  PubMed  Google Scholar 

  21. Storey E, Forrest SM, Shaw JH, Mitchell P, Gardner RJ. Spinocerebellar ataxia type 2: clinical features of a pedigree displaying prominent frontal-executive dysfunction. Arch Neurol. 1999;56:43–50.

    Article  CAS  PubMed  Google Scholar 

  22. Pedroso JL, de Freitas ME, Albuquerque MV, Saraiva-Pereira ML, Jardim LB, Barsottini OG. Should spinocerebellar ataxias be included in the differential diagnosis for Huntington’s diseases-like syndromes? J Neurol Sci. 2014;347(1–2):356–8.

    Article  PubMed  Google Scholar 

  23. Velázquez-Pérez L, Seifried C, Santos-Falco N, Abele M, Ziemann U, Almaguer LE, Martınez-Gongora E, Sánchez-Cruz G, Canales N, Perez-Gonzalez R, Velazquez-Manresa M, Viebahn B, von Stuckrad-Barre S, Fetter M, Klockgether T, Auburger G. Saccade velocity is controlled by polyglutamine size in spinocerebellar ataxia 2. Ann Neurol. 2004;56:444–7.

    Article  PubMed  Google Scholar 

  24. Pedroso JL, Braga-Neto P, Escorcio-Bezerra ML, Abrahão A, de Albuquerque MV, Filho FM, de Souza PV, de Rezende Pinto WB, Borges FR Jr, Saraiva-Pereira ML, Jardim LB, Barsottini OG. Non-motor and extracerebellar features in spinocerebellar ataxia type 2. Cerebellum. 2016.

  25. Castilhos RM, Souza AF, Furtado GV, Gheno TC, Silva AL, Vargas FR, Lima MA, Barsottini O, Pedroso JL, Godeiro Jr C, Salarini D, Pereira ET, Lin K, Toralles MB, Saute JA, Rieder CR, Quintas M, Sequeiros J, Alonso I, Saraiva-Pereira ML, Jardim LB. Huntington disease and Huntington disease-like in a case series from Brazil. Clin Genet. 2014;86(4):373–7.

    Article  CAS  PubMed  Google Scholar 

  26. Jacobi H, du Montcel ST, Bauer P, Giunti P, Cook A, Labrum R, Parkinson MH, Durr A, Brice A, Charles P, Marelli C, Mariotti C, Nanetti L, Panzeri M, Rakowicz M, Sulek A, Sobanska A, Schmitz-Hübsch T, Schöls L, Hengel H, Baliko L, Melegh B, Filla A, Antenora A, Infante J, Berciano J, van de Warrenburg BP, Timmann D, Szymanski S, Boesch S, Kang JS, Pandolfo M, Schulz JB, Molho S, Diallo A, Klockgether T. Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study. Lancet Neurol. 2015;14(11):1101–8.

    Article  PubMed  Google Scholar 

  27. Tezenas du Montcel S, Charles P, Goizet C, Marelli C, Ribai P, Vincitorio C, Anheim M, Guyant-Maréchal L, Le Bayon A, Vandenberghe N, Tchikviladzé M, Devos D, Le Ber I, N’Guyen K, Cazeneuve C, Tallaksen C, Brice A, Durr A. Factors influencing disease progression in autosomal dominant cerebellar ataxia and spastic paraplegia. Arch Neurol. 2012;69(4):500–8.

    Article  PubMed  Google Scholar 

  28. Jacobi H, Rakowicz M, Rola R, Fancellu R, Mariotti C, Charles P, Dürr A, Küper M, Timmann D, Linnemann C, Schöls L, Kaut O, Schaub C, Filla A, Baliko L, Melegh B, Kang JS, Giunti P, van de Warrenburg BP, Fimmers R, Klockgether T. Inventory of non-ataxia signs (INAS): validation of a new clinical assessment instrument. Cerebellum. 2013;12(3):418–28.

    Article  CAS  PubMed  Google Scholar 

  29. Schmitz-Hübsch T, Fimmers R, Rakowicz M, Rola R, Zdzienicka E, Fancellu R, Mariotti C, Linnemann C, Schöls L, Timmann D, Filla A, Salvatore E, Infante J, Giunti P, Labrum R, Kremer B, van de Warrenburg BP, Baliko L, Melegh B, Depondt C, Schulz J, du Montcel ST, Klockgether T. Responsiveness of different rating instruments in spinocerebellar ataxia patients. Neurology. 2010;74(8):678–84. doi:10.1212/WNL.0b013e3181d1a6c9.

    Article  PubMed  Google Scholar 

  30. Chan E, Charles P, Ribai P, Goizet C, Marelli C, Vincitorio CM, Le Bayon A, Guyant-Maréchal L, Vandenberghe N, Anheim M, Devos D, Freeman L, Le Ber I, N’Guyen K, Tchikviladzé M, Labauge P, Hannequin D, Brice A, Durr A, du Montcel ST. Quantitative assessment of the evolution of cerebellar signs in spinocerebellar ataxias. Mov Disord. 2011;26(3):534–8. doi:10.1002/mds.23531.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank the families who agreed to participate in this study. This work was supported by the following Brazilian agencies: CNPq—Conselho Nacional de Desenvolvimento Científico e Tecnológico—by the Project 78057/2012-1, FIPE-HCPA—Fundo de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre—by the Projects GPPG HCPA 12-0357 and 12-0396, and by INAGEMP—Instituto Nacional de Genética Médica Populacional. M.A. and L.D.L.C. were supported by FAPERGS. ERR, MA, ASPS, MLSP, and LBJ were supported by CNPq.

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Authors and Affiliations

  1. Serviço de Neurologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil

    Thais L. Monte

  2. Programa de Pós-Graduação em Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Thais L. Monte & Laura Bannach Jardim

  3. Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Estela R. Reckziegel, Marina C. Augustin, Amanda S. P. Silva & Lucas D. Locks-Coelho

  4. Setor de Neurologia Geral e Ataxias, Disciplina de Neurologia Clínica da UNIFESP—Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

    Orlando Barsottini & José L. Pedroso

  5. Laboratório de Epidemiologia de Malformações Congênitas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

    Fernando R. Vargas

  6. Departamento de Genética e Biologia Molecular, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

    Fernando R. Vargas

  7. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil

    Maria-Luiza Saraiva-Pereira & Laura Bannach Jardim

  8. Laboratório de Identificação Genética, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil

    Maria-Luiza Saraiva-Pereira & Laura Bannach Jardim

  9. Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Maria-Luiza Saraiva-Pereira

  10. Departamento de Matemática e Estatística, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Vanessa Bielefeldt Leotti

  11. Programa de Pós-Graduação em Epidemiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Vanessa Bielefeldt Leotti & Laura Bannach Jardim

  12. Departamento de Medicina Interna, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Laura Bannach Jardim

  13. Instituto Nacional de Genética Médica Populacional INAGEMP, Porto Alegre, Brazil

    Laura Bannach Jardim

  14. Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, 90.035-903, Brazil

    Maria-Luiza Saraiva-Pereira & Laura Bannach Jardim

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  1. Thais L. Monte
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  2. Estela R. Reckziegel
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  3. Marina C. Augustin
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  6. Orlando Barsottini
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  7. José L. Pedroso
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  10. Vanessa Bielefeldt Leotti
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  11. Laura Bannach Jardim
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on behalf of Rede Neurogenética

Contributions

1. Research project: (A) conception, (B) organization, (C) execution. 2. Statistical analysis: (A) design, (B) execution, (C) review and critique. 3. Manuscript preparation: (A) writing of the first draft, (B) review and critique.

T.L.M.: 1 B and C; 2 C; 3 B. E.R.R.: 1 C; 3 B. M.A.: 1 C; 3 B. A.S.P.S.: 1 C; 3 B. L.D.L.C.: 1 C; 3 B. O.B.: 1 C; 3 B. J.L.P.: 1 C; 3 B. F.R.V.: 1 C; 3 B. M.L.S.P.: 1 C; 3 B. V.B.L.T.: 1 B; 2 A, B, and C; 3B. L.B.J.: 1 A and B; 2 A and C; 3 A and B.

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Correspondence to Laura Bannach Jardim.

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Monte, T.L., Reckziegel, E.R., Augustin, M.C. et al. NESSCA Validation and Responsiveness of Several Rating Scales in Spinocerebellar Ataxia Type 2. Cerebellum 16, 852–858 (2017). https://doi.org/10.1007/s12311-017-0855-8

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