Spastic Ataxia Composite (SPAXCOM): A Scale to Evaluate the Progression of Subjects with Spasticity and Ataxia

Abstract

Background: Current clinical scales that track disease progression are more tailored to spasticity or ataxia, with limited sensitivity to change.

Objectives: The aim was to develop a sensitive and valid scale specifically geared towards optimized sensitivity to change and adapted to patients presenting with both spasticity and ataxia.

Methods: Longitudinal data from 127 spastic paraplegia type 7 (SPG7) and 112 autosomal recessive spastic ataxia Charlevoix-Saguenay (ARSACS) patients were collected within the multicenter PROSPAX study. Sensitivity to change over 2 years of 30 items from the Scale for the Rating and Assessment of Ataxias (SARA), Spastic Paraplegia Rating Scale (SPRS), and the Activities of Daily Living subscale of the Friedreich's Ataxia Rating Scale (FARS-ADL) was evaluated. Items that demonstrated the highest sensitivity to change were used to build the Spastic Ataxia Composite scale (SPAXCOM).

Results: With seven items, the SPAXCOM showed an effect size of 0.71, higher than reference scales (SARA: 0.43, SPRS: 0.42, FARS-ADL: 0.27). The SPAXCOM had a similar sensitivity to change for both genotypes and was more sensitive in participants with a SARA lower than 10 and within the intermediate disease stage (FARS-Disease Staging: 2-3.5). The SPAXCOM showed a high correlation with disease duration (r = 0.67 [0.60; 0.72]) and disease stage (r = 0.86 [0.83; 0.89]). Perception of improvement, stagnation, and worsening were associated with a mean yearly SPAXCOM change of 0.44 (-0.14; 1.01), 0.61 (0.19; 1.03), and 1.22 (0.96; 1.49), respectively.

Conclusion: The SPAXCOM is more sensitive to change and homogeneous across genotypes than the reference scales, allowing a reduction of the required sample size in future clinical trials. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: SPG7; ataxia; disease progression; spastic ataxia; spastic ataxia Charlevoix‐Saguenay type.

FIG. 1

Graphical summary of the methodology to build and assess the Spastic Ataxia Composite scale (SPAXCOM). ARSACS, autosomal recessive spastic ataxia of Charlevoix‐Saguenay; SARA, Scale for the Rating and Assessment of Ataxias; SPRS, Spastic Paraplegia Rating Scale; FARS‐ADL, Friedreich's Ataxia Rating Scale‐Activities of Daily Living; CI, confidence interval; IRT, item response theory. [Color figure can be viewed at wileyonlinelibrary.com]

FIG. 2

Effect sizes of the 30 items for the Scale for the Rating and Assessment of Ataxias (SARA), Spastic Paraplegia Rating Scale (SPRS), and Friedreich's Ataxia Rating Scale‐Activities of Daily Living (FARS‐ADL) scales. Effect sizes are reported for spastic paraplegia type 7 (SPG7) + autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) participants (all) and for each genotype separately. Items are sorted by their effect size on all participants. The effect size is the mean standardized annual change in score, calculated using linear regression for each patient separately. [Color figure can be viewed at wileyonlinelibrary.com]

FIG. 3

Effect sizes for the Spastic Ataxia Composite (SPAXCOM), Scale for the Rating and Assessment of Ataxias (SARA), Spastic Paraplegia Rating Scale (SPRS), and Friedreich's Ataxia Rating Scale‐Activities of Daily Living (FARS‐ADL) total scores, and their bootstrapped confidence intervals. (A) On all data. (B) Assessed separately according to baseline SARA scores. (C) Assessed separately on patients’ FARS Stage. The boxplot corresponding to patients with Mild stage is not shown, due to insufficient data (N = 25). Whiskers correspond to 1.5 times the interquartile range. (D) Assessed separately on both genotypes. [Color figure can be viewed at wileyonlinelibrary.com]

FIG. 4

Correlation between the Spastic Ataxia Composite scale (SPAXCOM), disease duration, and disease stage. (A) Scatterplot displaying the SPAXCOM score depending on disease duration, computed as the difference between age at baseline visit and age at symptoms onset (N = 232). (B) Scatterplot displaying the SPAXCOM score depending on Friedreich's Ataxia Rating Scale (FARS) Stage (N = 239). [Color figure can be viewed at wileyonlinelibrary.com]