Robot-assisted gait training for patients with hereditary ATTR amyloidosis: a single-arm study

Background Patients with advanced-stage hereditary ATTR (ATTRv) amyloidosis who develop gait disturbance as a result of progressive polyneuropathy often respond suboptimally to current disease-modifying agents. This study aimed to evaluate the potential effects and safety of gait training with the Hybrid Assistive Limb (HAL) in patients with ATTRv amyloidosis. Methods All participants had a genetically and pathologically confirmed diagnosis of ATTRv amyloidosis. Participants completed 9 days of robot-assisted gait training (RAGT) with HAL. The primary outcome was the 10-m walking time (10MWT), and the secondary outcomes were the 2-min walking distance (2MWD) and the Neuropathy Impairment Score (NIS). All measurements were performed before the first training session on day 1 and again on the day after the final session. Results Ten participants were enrolled. The mean age at enrollment was 56.9 ± 9.2 years (mean ± standard deviation, SD). Five of the ten participants had undergone pacemaker implantation. At baseline, the mean 10MWT was 15.2 ± 6.1 s, the mean 2MWD was 88.3 ± 32.8 m, and the mean total NIS score was 55.8 ± 24.2 (mean ± SD). The absolute pre–post changes were 3.8 s ± 3.9 s for the 10MWT, 16.9 m ± 11.0 m for the 2MWD, and 2.5 points ± 3.6 points for the NIS (mean ± SD). Improvement rates were 22.1% ± 13.4% for the 10MWT, 23.9% ± 21.3% for the 2MWD, and 4.3% ± 5.0% for the NIS (mean ± SD). The effect sizes, expressed as Hedges’ g, were largest for the 2MWD (1.40, 95% confidence interval [CI]: 0.53–2.24), followed by the 10MWT (−0.89, 95% CI: −1.57 – −0.17) and the NIS (−0.63, 95% CI: −1.25 – 0.02). No serious adverse events occurred, and no pacemaker abnormalities or interference were detected. Conclusion RAGT with HAL was associated with short-term improvements in gait function among patients with ATTRv amyloidosis and gait disturbance. However, the durability of these improvements remains unknown. Clinical trial registration https://jrct.mhlw.go.jp/latest-detail/jRCTs032240462 , jRCTs032240462.