Cybernic treatment with wearable cyborg Hybrid Assistive Limb (HAL) improves ambulatory function in patients with slowly progressive rare neuromuscular diseases: a multicentre, randomised, controlled crossover trial for efficacy and safety (NCY-3001)

Takashi Nakajima,Toshio Saitô ,Yusuke Ando ,Yoshihiro Ishikawa ,Takashi Maéno ,Takeshi Miura ,Yôko Kobayashi ,Shigeo Takata ,Masashi Akiyama ,Koichiro Komai ,Michiya Ito,Jun Matsuda,Chiho Ishida,Akira Tamaoka,Tetsuhiko Ikeda,Takako Saotome,Masanori Nakagawa,Masahiro Shingu,Mitsuya Morita,Kayoko Saito,Yoshiyuki Sankai,Kazuhiro Ishii,Shinichiro Maeshima,Yumiko Kawaguchi,Tatsuya Mima,Hisako Endo,Tetsuo Ikai,Tomohiro Hayashi,Hiroaki Kawamoto

doi:10.1186/s13023-021-01928-9

Abstract

BackgroundRare neuromuscular diseases such as spinal muscular atrophy, spinal bulbar muscular atrophy, muscular dystrophy, Charcot-Marie-Tooth disease, distal myopathy, sporadic inclusion body myositis, congenital myopathy, and amyotrophic lateral sclerosis lead to incurable amyotrophy and consequent loss of ambulation. Thus far, no therapeutic approaches have been successful in recovering the ambulatory ability. Thus, the aim of this trial was to evaluate the efficacy and safety of cybernic treatment with a wearable cyborg Hybrid Assistive Limb (HAL, Lower Limb Type) in improving the ambulatory function in those patients.ResultsWe conducted an open-label, randomised, controlled crossover trial to test HAL at nine hospitals between March 6, 2013 and August 8, 2014. Eligible patients were older than 18 years and had a diagnosis of neuromuscular disease as specified above. They were unable to walk for 10 m independently and had neither respiratory failure nor rapid deterioration in gait. The primary endpoint was the distance passed during a two-minute walk test (2MWT). The secondary endpoints were walking speed, cadence, and step length during the 10-m walk test (10MWT), muscle strength by manual muscle testing (MMT), and a series of functional measures. Adverse events and failures/problems/errors with HAL were also evaluated. Thirty patients were randomly assigned to groups A or B, with each group of 15 receiving both treatments in a crossover design. The efficacy of a 40-min walking program performed nine times was compared between HAL plus a hoist and a hoist only. The final analysis included 13 and 11 patients in groups A and B, respectively. Cybernic treatment with HAL resulted in a 10.066% significantly improved distance in 2MWT (95% confidence interval, 0.667–19.464; p = 0.0369) compared with the hoist only treatment. Among the secondary endpoints, the total scores of MMT and cadence at 10MWT were the only ones that showed significant improvement. The only adverse effects were slight to mild myalgia, back pain, and contact skin troubles, which were easily remedied.ConclusionsHAL is a new treatment device for walking exercise, proven to be more effective than the conventional method in patients with incurable neuromuscular diseases.Trial registration: JMACTR, JMA-IIA00156

Highlights

Rare neuromuscular diseases such as spinal muscular atrophy, spinal bulbar muscular atrophy, muscular dystrophy, Charcot-Marie-Tooth disease, distal myopathy, sporadic inclusion body myositis, congenital myopathy, and amyotrophic lateral sclerosis lead to incurable amyotrophy and consequent loss of ambulation
Six patients were excluded for the following reasons: in group A, one patient voluntarily withdrew from the trial prior to the last 2-min walk test (2MWT) during the treatment period, and one patient was excluded because of an unmet 2MWT; in group B, one patient withdrew from the trial before the last 2MWT owing to pneumonia, one was excluded owing to an unmet 2MWT, and two discontinued the trial prior to the last 2MWT owing to the investigators’ judgment that it was too difficult for these subjects to continue the trial
This study showed significant improvements in gait function in patients with incurable neuromuscular diseases after nine interactive biofeedback (iBF)-based cybernic treatments with Hybrid Assistive Limb (HAL)-HN01 compared with walking exercises with a hoist only

Summary

Introduction

Rare neuromuscular diseases such as spinal muscular atrophy, spinal bulbar muscular atrophy, muscular dystrophy, Charcot-Marie-Tooth disease, distal myopathy, sporadic inclusion body myositis, congenital myopathy, and amyotrophic lateral sclerosis lead to incurable amyotrophy and consequent loss of ambulation. The motor units are controlled by descending tracts of the central nervous system. There are a number of diseases that impair voluntary movements, and can occur at specific sites from the central nervous system to the motor unit. Previous studies, such as Ramón y Cajal [2], showed that in animal models, damaged neurons in the central nervous system (CNS) did not regenerate and synapses did not reconnect. Most rehabilitation programs for patients with motor impairment have not directly aimed to restore the function but rather only used the residual function to acquire compensatory activities [3]

Methods

Results

Discussion

Conclusion