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The hybrid assistive limb is the world’s first wearable robot device that provides effective gait assistance according to voluntary intention.
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Rehabilitation does not only assist ALS patients in managing disease-related symptoms, but help them enjoy a fulfilling life despite the shortened lifespan.
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Walking distance significantly increased on the 2 min walk test after HAL training.
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HAL can possibly preserve gait ability in ALS patients.
Abstract
Objective
The Hybrid Assistive Limb (HAL; CYBERDYNE, Inc., Japan) is a wearable robot device that provides effective gait assistance according to voluntary intention by detecting weak bioelectrical signals of neuromuscular activity on the surface of the skin. We used HAL for patients with amyotrophic lateral sclerosis (ALS) to determine whether HAL training had an effect on their gait ability.
Methods
We conducted a single-center, single-arm, observational study. Patients with ALS underwent HAL training once per day (20–40 min per session) for 9–10 days for at least 4 weeks. Gait ability was evaluated using the 2-minute walk test, the 10-meter walk test without the assistance of HAL, and activities of daily living (ADL) using the Barthel Index and Functional Independence Measures before and after a full course of HAL training.
Results
There were no dropouts or adverse events during the observation period. Gait function improved after HAL training. The 2-minute walk test revealed a mean gait distance of 73.87 m (36.65) at baseline and 89.9m (36.70) after HAL training (p = 0.004). The 10-meter walk test showed significantly improved cadence, although gait speed, step length on the 10-m walk, or ADL measurements did not change significantly.
Conclusions
Although HAL is not a curative treatment for ALS, our data suggest that HAL may be effective in ameliorating and preserving gait ability in patients with ALS.
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease characterized by the degeneration of both upper and lower motor neurons, leading to muscle weakness, dysphagia, and respiratory disorders. It generates substantial burden on patients and caregivers. The mechanisms underlying the development of ALS are poorly understood. Two approved disease-modifying drug therapies, riluzole and edaravone, are known to slow its progression. Nevertheless, its management is primarily symptomatic, including muscle relaxants for spasticity, speech therapy for dysarthria, swallowing training for dysphagia, and conventional physical therapy for reducing pain and loss of muscle strength or function [
]. However, recent studies indicate that rehabilitation can assist ALS patients in managing disease-related symptoms, thereby helping patients perform their activities more independently and safely and enjoy a fulfilling life despite the shortened lifespan [
]. Most studies evaluated the effect of the interventions on gait through functional scales, and only one study quantitively evaluated the effectiveness of the intervention by using measurements such as 6 min walk tests [
]. Endurance/aerobic exercise improved the ALS Functional Rating Scale-Revised (ALSFRS-R), and all types of intervention improved the forced vital capacity (%FVC). However, there were no changes in quality of life, muscle strength, and fatigue. The effect of the type and magnitude of rehabilitation on motor units in patients with ALS remains unclear. The spectrum and progression of the condition varies across patients, suggesting that the rehabilitation approach should be planned individually and changed carefully according to the disease stage of each patient. The rehabilitation approach appears to be the most important in ALS; nevertheless, there are very limited interventions because of the progressive nature of ALS.
The Hybrid Assistive Limb (HAL-ML05; CYBERDYNE, Inc. Japan) is a unique wearable exoskeleton robot device that provides physical gait assistance according to bioelectrical signals (BES) of neuromuscular activity on the surface of the skin caused by voluntary intention [
]. HAL was developed based on the interactive biofeedback theory; it allows both voluntary and autonomous modes of action to support gait training, permitting patients with severe disabilities to receive higher dosages and intensities of gait training compared to those available with conventional physical therapy [
]. Several previous studies have shown its efficacy for disorders such as stroke, spinal cord injuries, musculoskeletal diseases, and other diseases affecting gait ability [
A randomized and controlled crossover study investigating the improvement of walking and posture functions in chronic stroke patients using HAL exoskeleton - the HALESTRO study (HAL-Exoskeleton STROke Study).
HAL® exoskeleton training improves walking parameters and normalizes cortical excitability in primary somatosensory cortex in spinal cord injury patients.
A newly developed robot suit hybrid assistive limb facilitated walking rehabilitation after spinal surgery for thoracic ossification of the posterior longitudinal ligament: a case report.
The voluntary driven exoskeleton Hybrid Assistive Limb (HAL) for postoperative training of thoracic ossification of the posterior longitudinal ligament: a case report.
Mizui D, Nakai Y, Okada H, Kanai M, Yamaguchi K: [A case of spinal and bulbar muscular atrophy with improved walking ability following gait training using the hybrid assistive limb (HAL)]. Rinsho Shinkeigaku 2019, 59(3):157-159.
] Minor and transient side effects have occurred; however, severe adverse events have not been reported till date.
In Japan, HAL was officially approved in 2015 as a new medical treatment device for patients with rare intractable neuromuscular diseases, including ALS, spinal muscular atrophy, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth disease, muscle dystrophy, distal myopathy, and sporadic inclusion body myositis. These neuromuscular diseases are very rare, and therefore there is limited data on the efficacy of HAL. The efficacy of HAL-based training for improving gait ability and its benefits in patients with ALS has not been clarified.
The principal aim of this study was to determine whether HAL training was effective for rehabilitation of gait ability in ALS patients, and to clarify its expected effect.
2. Methods
2.1 Experimental subjects
Patients who were diagnosed with ALS by board-certified neurologists in our department from January to December 2019 were eligible for this study. The inclusion criteria were as follows: (1) age ≥ 18 years; (2) unsteady gait with the ability to walk more than 10 m with assistance from a caregiver and/or a walker; (3) stable gait ability for the previous 3 months; and (4) ability to fit the wearable robot suit HAL (height 150–190 cm; weight 40–100 kg). The exclusion criteria were as follows: (1) communication difficulties due to impaired consciousness and/or cognitive dysfunction (mini-mental state examination [MMSE] score < 20 points); (2) difficulty performing gait training exercises due to severe dyspnea, and heart or orthopedic disease; (3) severe hepatic/renal failure; (4) gait impairment due to cerebral or muscle disorders other than ALS; (5) new treatment within one month of study initiation, including gait training rehabilitation program, all steroid treatments except inhaled and topical medications, riluzole, sodium valproate, and other drugs for the control of ALS progression; (6) history of bruising, fractures, trauma, and other diseases requiring hospitalization within 3 months of study initiation; (7) pregnancy or plans for pregnancy; (8) skin trouble precluding attachment of the HAL sensor pad; and (9) dementia.
2.2 Ethical approval
This single-center, single-arm observational study was conducted at the Department of Neurology and the Department of Rehabilitation Medicine, Toho University Faculty of Medicine (Tokyo, Japan). This study protocol was approved by the Ethics Committee of Toho University Omori Medical Center (approval number: M18122). Written informed consent was obtained from all participants.
2.2 Experimental design and procedures
The training was performed by two physiotherapists and a doctor who was trained to use the HAL system. The gait training program using HAL in our hospital consisted of one session per day (20–40 min per session), 2–3 days a week for at least 4 weeks but no more than 5, according to the patients’ conditions. One course of HAL training consisted of a total of 9–10 days. On other days of HAL training, patients underwent conventional gait training without HAL and physical therapy.
The gait training program with HAL was implemented using a treadmill. Training started with Cybernic Voluntary Control mode providing suit operation using BES generated by muscle activities and recorded by skin-surface electromyographic electrodes placed on the patients’ iliopsoas, quadriceps, hamstrings, and gluteal muscles. The settings were determined according to the severity of muscle contraction for each patient so that the patients could easily raise their lower extremities. During training, the physiotherapist checked the BES and adjusted the motor assist level for each patient. For safety reasons, support from the handrail of the treadmill and a walking device with a harness were used, and two physiotherapists supported the patients and prevented falls. If patients experienced respiratory discomfort during training, or fatigue and muscle pain on the day following training, the treadmill speed was adjusted appropriately (Fig. 1).
Fig. 1HAL-based gait training. The patient wears HAL and walks on the treadmill with the body weight support system suspended. Training started with the Cybernic Voluntary Control mode. Patients were protected from falls using a mobile hoist during HAL training and were supported by physiotherapists who checked the speed of the treadmill and the motor assist level of HAL. Moreover, the speed and assist level were adjusted to the patients’ conditions as needed.
Baseline measures included demographic data pertaining to the following: lesion of onset, duration of disease, riluzole prescription, percutaneous gastrostomy feeding tube (PEG), noninvasive ventilation (NIV), MMSE score, ALS severity, and %FVC. The gait ability (2-minute walk test [2 MWT] and 10 m walk test [10 MWT]), and activities of daily living (ADL) were assessed prior to the start of HAL training. In the 2 MWT, the distance that patients could walk for 2 min was measured. In the 10 MWT, the walking time was measured and the number of steps required to walk 10 m was counted in order to calculate walking speed (m/s) and step length (m/step). The cadence (steps/s) was calculated from the walking time and number of steps. In both the 2 MWT and 10 MWT, the patients walked on a flat floor at their self-selected maximum speed without wearing HAL. Assistance such as handrails, walkers, and caregivers’ help were allowed if needed. ADL was assessed using the Barthel Index (BI) and Functional Independence Measure (FIM). ALS severity was assessed using the ALSFRS-R. Gait ability assessments were conducted by physical therapists trained to perform standardized assessment procedures. These outcome measures were evaluated before and after the full course of HAL training.
In order to evaluate the effectiveness of training with HAL on gait ability, the outcome measures including the walking distance of 2 MWT, walking speed, step length, cadence of 10 MWT, and the scores of BI and FIM, were compared before and after training using the paired t-test. Statistical significance was set at p < 0.05.
3. Results
We included 11 ALS patients with gait disorders (three men and eight women). At baseline, (the time of study enrolment) the mean age (SD) was 63.9 (11.5) years. The details of patient characteristics and demographics are summarized in Table 1. The onset lesions were as follows: one patient with a bulbar lesion, three patients with disorders of the upper extremities, six patients with disorders of the lower extremities, and one patient with respiratory disorders. The mean duration of ALS was 42.0 (25.7) months. The mean ALSFRS-R was 34.73 (6.44); mean %FVC was 84.6% (26.74%); mean BI score was 75.45 (18.09) (range, 45–95); and mean FIM score was 108.45 (15.81) (range, 79–122). Out of the 11 participants, one received nutritional support by PEG, and two used NIV intermittently. None of the patients started using PEG or NIV during the observation period. All patients were assessed using the MMSE and they had no cognitive dysfunction. None of the patients who fulfilled the study criteria declined participation, and there were no dropouts. No training-related severe adverse events or accidents occurred.
Data from the assessments at baseline and immediately after the completion of training are presented in Table 2 and Fig. 2. On the 2 MWT, 10 out of 11 patients showed an improvement in walking distance. The mean walking distance changed significantly from 73.87 m (36.65) (range, 10.0–132.9) at baseline to 89.94 m (36.70) (range, 31.8–147.0) after training (p = 0.004). On the 10 MWT, eight out of 11 patients showed improved walking speed from baseline to after training. The average speed was 0.84 m/sec (0.43) (range, 0.24–1.70) at baseline and 0.92 m/sec (0.43) (range, 0.26–1.54) after training (p = 0.07). All but two patients increased their step length or remained the same. The average step length was 0.46 m (0.1) (range, 0.22–0.67) at baseline and 0.48 m (0.13) (range, 0.19–0.60) after training (p = 0.17). Significant improvements were observed in the cadence. The mean cadence increased from 1.71 steps/sec (0.50) (range, 0.84–2.56) at baseline to 1.81 steps/sec (0.50) (range, 0.96–2.56) after training (p = 0.04). ADL was maintained at almost the same condition, without significant worsening in both BI and FIM. The average scores after training were 78.18 (16.17) (range, 50–100) for BI (p = 0.05) and 110.1 (16.73) (range, 80–124) for FIM (p = 0.20) . The severity of ALS did not change significantly throughout the observation period. The mean ALSFRS-R scores remained constant before and after training, at 34.55 (7.06) (range, 23–45) after training (p = 0.62). Respiratory function remained stable, mean %FVC was 84.64% (26.74%) (range, 39.2–122.1) at baseline, and 84.59 (27.31%) (range, 37.2–122.3) after the course of training (p = 0.99).
Fig. 2Change of functional mobility of gait, and activities of daily living for patients after HAL training. On the 2-minute walk test, an increased walking distance was observed in 10 of the 11 patients. Furthermore, the mean walking distance significantly improved after HAL training. On the 10-m walk test, nine of 11 patients increased cadence and significantly improved the average cadence after the training. However, the average walking speed and step length did not significantly change after the training. Both the Barthel Index (BI) and the Functional Independent Measure (FIM) showed no significant difference between the periods before and after HAL training. Despite the absence of a significant difference, there was an improvement or preservation trend in both.
The walking distance significantly increased on the 2 MWT after HAL training. Cadence also improved significantly on the 10 MWT. Although the speed and step length did not improve significantly, the trend improved, or was maintained, in most patients after HAL training. In the ADL evaluation, neither BI nor FIM showed significant differences from before to after HAL training. Despite the absence of a significant difference, a tendency towards improvement was observed on both scales. The total BI score slightly increased in six and remained stable in four of 11 patients. A similar tendency was seen in FIM: the total score increased in five patients and remained stable in four patients. The mean ALSFRS-R scores remained stable, suggesting that the condition of the disease did not change during the observation period.
The HAL for medical use (lower limb type) is a wearable robot designed to support the paretic limb, predict voluntary control of the knee and hip joint by detecting BES on the surface of the skin, and assist in muscle movement. This system estimates motion intention, enhances the wearer’s motions in real time, and is a well-controlled appropriate burden for each patient. The device allows the wearer with gait disturbances due to muscle weakness of the lower extremities to walk passively and repeatedly [
]. Intentionally repeated movements with HAL enable wearers to walk almost normally, leading to a type of errorless learning and training based on synaptic plasticity, known as Hebbian theory [
]. The adjusted burden provides the wearers with training that is pleasant and increases the amount of training per unit time. This results in use-dependent plasticity and prevents disuse of muscle atrophy. After HAL training, patients regain almost normal gait ability and can maintain the muscle strength needed to walk normally. The amelioration of endurance led to an increased walking distance on the 2 MWT.
In ALS, the upper motor neurons increase synaptic stimuli to spinal motor neurons for maintaining muscle strength. This overactivity is thought to cause the progression of the degeneration of motor neurons [
]. By adjusting the stimulation for each motor unit according to the degree of motor unit degeneration, not only do the symptoms improve, but the speed of degeneration of motor neurons may also be reduced. The interactive biofeedback effect of HAL from the perspective of changes in cortical activity may contribute to the improvement and preservation of gait ability in patients with ALS. The process of motor learning using HAL is closely related to the sensory signals sent back through the thalamus to the frontoparietal networks, involving the primary sensory cortex. Output signals from the motor cortex to the muscles are reciprocally interconnected by the basal ganglia and cerebellar circuits. HAL was formulated using a hypothesis of the brain network model including cortico-cortical, cortico-striatal-thalamic, and cortico-cerebellar-thalamic networks, all of which are potentially activated by the biofeedback effect. The amelioration of cadence in our study may have been caused by intentionally repeated movements and the interactive biofeedback effect of HAL [
Several studies have demonstrated the efficacy of neurorehabilitation programs addressing use-dependent neuroplasticity, including constraint-induced movement therapy and robot rehabilitation, including HAL in stroke patients. Repetitive training eliciting voluntary movement is thought to result in more effective functional recovery than that elicited by passive exercise training. In this context, HAL-assisted treatment may facilitate neuroplasticity associated with comprehensive motor learning in patients with ALS and stroke [
]. Considering the progressive nature of ALS, our study demonstrated the effect of neuroplasticity-induced HAL-assisted rehabilitation and amelioration of gait ability with improvement of walking distance and cadence in patients with ALS. Throughout the observation period, there were no adverse events, and all participants completed the course.
Our study has several limitations. This was a single-arm observational study with a small number of patients. There was no control group of patients treated with conventional physical therapy without HAL. Because we analyzed patients with only one course of HAL training and did not include a follow-up, this study did not demonstrate the long-term efficacy of HAL training for ALS patients. Well-designed controlled studies, followed by larger studies using qualitative approaches, are needed to explore the effect of HAL. The detailed mechanism of preservation of gait ability in patients with ALS was not investigated in this study. Considering the progressive nature of ALS, the long-term effects of HAL, the validation of upper and lower neuron signs in each patient may have resulted differently from those of this study. Further evaluation of the adaptation criteria for patients with ALS is needed.
In conclusion, we report the possibility that the use of the HAL system for ALS patients is effective when used for gait training in rehabilitation settings. It can bring about temporary amelioration and preservation of gait ability. Although HAL is not a curative treatment for ALS, our data suggest that such training may improve gait function in patients with ALS.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
A randomized and controlled crossover study investigating the improvement of walking and posture functions in chronic stroke patients using HAL exoskeleton - the HALESTRO study (HAL-Exoskeleton STROke Study).
HAL® exoskeleton training improves walking parameters and normalizes cortical excitability in primary somatosensory cortex in spinal cord injury patients.
A newly developed robot suit hybrid assistive limb facilitated walking rehabilitation after spinal surgery for thoracic ossification of the posterior longitudinal ligament: a case report.
The voluntary driven exoskeleton Hybrid Assistive Limb (HAL) for postoperative training of thoracic ossification of the posterior longitudinal ligament: a case report.
Mizui D, Nakai Y, Okada H, Kanai M, Yamaguchi K: [A case of spinal and bulbar muscular atrophy with improved walking ability following gait training using the hybrid assistive limb (HAL)]. Rinsho Shinkeigaku 2019, 59(3):157-159.
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