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. 2023 Oct;10(10):1833-1843.
doi: 10.1002/acn3.51875. Epub 2023 Aug 17.

Disease progression of spinocerebellar ataxia types 1, 2, 3 and 6 before and after ataxia onset

Heike Jacobi  1 , Tamara Schaprian  2 , Tanja Schmitz-Hübsch  3 , Matthias Schmid  2   4 , Thomas Klockgether  2   5 ; EUROSCA and RISCA Study Groups
Affiliations

Disease progression of spinocerebellar ataxia types 1, 2, 3 and 6 before and after ataxia onset

Heike Jacobi et al. Ann Clin Transl Neurol. 2023 Oct.

Abstract

Objective: Our aim was to study the evolution of ataxia and neurological symptoms before and after ataxia onset in the most common spinocerebellar ataxias (SCAs), SCA1, SCA2, SCA3 and SCA6. We therefore jointly analysed the data of the EUROSCA and RISCA studies, which recruited ataxic and non-ataxic mutation carriers.

Methods: We used mixed effect models to analyse the evolution of Scale for the Rating and Assessment of Ataxia (SARA) scores, SCA Functional Index (SCAFI) and Inventory of Non-Ataxia Signs (INAS) counts. We applied multivariable modelling to identify factors associated with SARA progression. In the time interval 5 years prior to and after ataxia onset, we calculated sensitivity to change ratios (SCS) of SARA, SCAFI and INAS.

Results: 2740 visits of 677 participants were analysed. All measures showed non-linear progression that was best fitted by linear mixed models with linear, quadratic and cubic time effects. R2 values indicating quality of the fit ranged from 0.70 to 0.97. CAG repeat was associated with faster progression in SCA1, SCA2 and SCA3, but not SCA6. 5 years prior to and after ataxia onset, SARA had the highest SCS of all measures with a mean of 1.21 (95% CI: 1.20, 1.21) in SCA1, 0.94 (0.93, 0.94) in SCA2 and 1.23 (1.22, 1.23) in SCA3.

Interpretation: Our data have important implications for the understanding of disease progression in SCA1, SCA2, SCA3 and SCA6 across the lifespan. Furthermore, our study provides information for the design of interventional trials, especially in pre-ataxic mutation carriers close to ataxia onset and patients in early disease stages.

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Conflict of interest statement

None of the authors reports conflicts of interest regarding this manuscript.

Figures

Figure 1
Figure 1
Individual trajectories of SARA evolution in SCA1, SCA2, SCA3 and SCA6. INAS, Inventory of Non‐Ataxia Signs; SARA, Scale for the Assessment and Rating of Ataxia; SCA, spinocerebellar ataxia; SCAFI, SCA Functional Index.
Figure 2
Figure 2
Loess plots of progression of COAs for each SCA type. SCA, spinocerebellar ataxia; SARA, Scale for the Assessment and Rating of Ataxia; SCAFI, SCA Functional Index; INAS, Inventory of Non‐Ataxia Signs.
Figure 3
Figure 3
Progression of COAs by linear mixed models for each SCA type. INAS, Inventory of Non‐Ataxia Signs; SARA, Scale for the Assessment and Rating of Ataxia; SCA, spinocerebellar ataxia; SCAFI, SCA Functional Index.
Figure 4
Figure 4
Effect of the expanded allele on SARA progression in SCA1, SCA2, SCA3 and SCA6. SARA, Scale for the Assessment and Rating of Ataxia; SCA, spinocerebellar ataxia.
See this image and copyright information in PMC

References

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