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Progression Rate of Neurological Deficits in a 10-Year Cohort of SCA3 Patients

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Abstract

Spinocerebellar ataxia 3 is an untreatable CAG repeat expansion disorder whose natural history is not completely understood. Our aims were to describe the progression of neurological manifestations in a long-term cohort of spinocerebellar ataxia 3, and to verify if CAG expanded repeat, gender, and age at onset were associated with the rate of progression. Patients entered the study between 1998 and 2005 and were seen until 2007. On each visit, the validated NESSCA scale, an inventory of 18 neurological manifestations, was applied. Scores observed in each year of disease duration produced a Growth Curve, which was analyzed through the random coefficients model. Scores obtained in some individual items were described through multi-state Markov models. One hundred fifty-six patients (78 families) were recruited; 28 were lost, and 23 died. Mean (sd) ages at onset and at baseline were 32.8 (10.6) and 40.7 (12.8) years; median (range) expanded CAGn was 74 (67–85). Three hundred fifteen NESSCA evaluations were performed, comprising disease durations from zero to 34 years. The 105 patients who completed the study were seen over 5 (sd = 2.4) years at intervals of 2.5 (sd = 1.5) years. The trajectory of NESSCA obtained for the overall group increased by 1.26 points per year. This slope increased by 0.15 points per each additional CAG in the expanded repeat (p < 0.0002) and decreased by 0.03 points per each additional year of age at onset (p = 0.005). NESSCA worsened steadily, producing linear trajectories, which were faster among patients with longer expanded repeats (>74) and with lower ages at onset (<34 years).

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Acknowledgments

We are grateful to the patients who agreed to participate in this study. We also thank Maria Luiza Saraiva Pereira, Isabel Silveira, and Jorge Sequeiros for the molecular analyses performed in these patients. This study was supported by CNPq, CAPES, FAPERGS, INAGEMP, and FIPE-HCPA. L.B. Jardim was supported by CNPq.

Conflict of Interest

The authors state that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Laura Bannach Jardim

  2. Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Lisiane Hauser, Renan Xavier & Suzi Camey

  3. Postgraduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Laura Bannach Jardim

  4. Postgraduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Suzi Camey

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

    Laura Bannach Jardim

  6. Neurology Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90.035-903, Porto Alegre, Brazil

    Jonas Alex Morales Saute, Carlos Roberto Mello Rieder & Thais Lampert Monte

  7. Psychiatry Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90.035-903, Porto Alegre, Brazil

    Christian Kieling

  8. Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Vanessa Bielefeld Leotti Torman

Authors
  1. Laura Bannach Jardim
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  2. Lisiane Hauser
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  3. Christian Kieling
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  4. Jonas Alex Morales Saute
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  5. Renan Xavier
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  6. Carlos Roberto Mello Rieder
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  7. Thais Lampert Monte
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  8. Suzi Camey
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  9. Vanessa Bielefeld Leotti Torman
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Corresponding author

Correspondence to Laura Bannach Jardim.

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Table e-1

Parameter estimations used in the adjustment of growth curves (DOC 41 kb)

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Jardim, L.B., Hauser, L., Kieling, C. et al. Progression Rate of Neurological Deficits in a 10-Year Cohort of SCA3 Patients. Cerebellum 9, 419–428 (2010). https://doi.org/10.1007/s12311-010-0179-4

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