# 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

## TL;DR

Researchers evaluated a modified version of a symptom inventory for Friedreich's ataxia over 12 years, finding it useful for tracking non-ataxia signs in patients.

## Contribution

The study introduces a modified INAS sum that shows better responsiveness in tracking disease progression over time.

## Key findings

- The modified INAS sum increased by 0.68 points/year over 12 years, showing significant progression.
- The modified INAS sum had higher responsiveness (SRM) in non-ambulatory patients and children compared to other groups.
- The modified INAS sum correlated strongly with existing outcome measures but showed better responsiveness over 5 years.

## Abstract

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.

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

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)

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).

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.