Analysis of a Modified Version of the Inventory of Non-Ataxia Signs Over 12 Years in Patients with Friedreich's Ataxia in the EFACTS Study.

BACKGROUND

Friedreich's ataxia is a rare, neurodegenerative, multisystem disorder. While ataxia is a hallmark, non-ataxia signs, including muscle weakness, spasticity, and dysphagia are equally disabling. The Inventory of Non-Ataxia Signs (INAS) is a symptom list transformable to a 16-item count.

OBJECTIVE

To evaluate the responsiveness of a modified INAS in this population.

METHODS

Participants were drawn from the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS). The modified INAS count (presence/absence, 0-16 scale) and modified INAS sum (severity-weighted, 0-84 scale) were evaluated using linear mixed-models and standardized response means (SRMs). Items rare (<5%) and uncharacteristic in Friedreich's ataxia were excluded (chorea, myoclonus, fasciculations, resting tremor, rigidity)

RESULTS

A total of 1129 participants (mean age, 32.3 years) were assessed for up to 12 years. The mean modified INAS count was 4.6 (±2.2) and modified INAS sum 15.1 (± 9.9). Both correlated strongly with existing outcome measures. Longitudinally, the modified INAS count increased by 0.13 points/year (95% CI 0.12, 0.14; P < 0.001) and modified INAS sum by 0.68 points/year (95% CI 0.64, 0.72; P < 0.001). The modified INAS sum demonstrated greater responsiveness, with SRMs of 0.26, 0.38, 0.53, and 0.80 at 1, 2, 3, and 5 years, respectively, compared with 0.16, 0.27, 0.31, and 0.46 for the modified INAS count. In non-ambulatory patients and children, responsiveness of the modified INAS sum was higher (SRM 0.82 and 1.7 at 5 years, respectively).

CONCLUSIONS

The modified INAS sum showed good responsiveness over 5 years but not over 1-3 years. It may supplement existing outcome measures, contributing to holistic assessment of this multisystem disease, especially in non-ambulatory patients, in whom ataxia-focused measures may show ceiling effects, and children, who typically progress faster. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.