Lokomat Therapy and robot assisted gait training

The content of this document is OFFICIAL. Please note: The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters, they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters

Research question: What is the efficacy of Lokomat therapy to improve gait/gross motor skills in different populations (CP, SCI, ABI)? Is there any particular level of ability that responds more favourably to the therapy, eg in CP, does the Gross Motor Functional Classification Scale level make a difference to outcomes? Is there any evidence for long-term efficacy, i.e. are gains maintained once therapy stops? Is Lokomat more effective than other types of traditional physiotherapy to improve gait? Is there any evidence of a particular intensity of Lokomat therapy being more effective, e.g. once/twice a week therapy is required? Is there any evidence about the duration of therapy required to see meaningful and long-lasting change? Is there any evidence whether Lokomat is more effective as a rehabilitation tool (eg soon after onset of SCI or ABI), compared to a maintenance support (more than 2 years post-onset) or an early intervention support (for children with congenital conditions)?

Date: 22/12/2022 Requestor: Jean redacted: s22(1)(a)(ii) - irrelevant material Endorsed by: Jane redacted: s22(1)(a)(ii) - irrelevant material Researcher: Aaron redacted: s22(1)(a)(ii) - irrelevant material Cleared by: Aaron redacted: s22(1)(a)(ii) - irrelevant material Review date: 6/2024

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Official For Internal Use Only

Lokomat Therapy: 1
- Contents: 2
- Summary: 2
- Lokomat therapy: 3
  - Sub heading: Error! Bookmark not defined.
- Evidence for different conditions: 4
  - Spinal cord injury: 4
  - Acquired Brain Injury (including stroke): 6
  - Multiple Sclerosis: 7
  - Parkinson’s Disease: 8
  - Cerebral Palsy: 8
- Risks and contra-indications: 9
  - Sub heading: Error! Bookmark not defined.
- References: 11

Summary

This paper examines evidence of efficacy for the use of the Lokomat device in improving gait and motor function in people with Cerebral Palsy (CP), Multiple Sclerosis (MS), Parkinson’s disease, Spinal Cord Injury (SCI) and stroke. Most reviews combine results for Lokomat and other types of robot assisted gait training (RAGT). I have noted where results could be separated. Due to the large body of evidence, I have based conclusions on mostly systematic reviews. There are certainly primary or other secondary studies which were not accounted for in this research which may inform different conclusions. RAGT is generally shown to be effective in improving some measures of gait and motor function for the populations reviewed. However, studies disagree on whether RAGT is independently effective or should be combined with other physiotherapy treatments. Evidence is weaker in some areas. For example, we were only able to find two systematic reviews for the use for RAGT for people with Parkinson’s disease, and both reviews were completed by the same team of researchers. Other conditions are more thoroughly researched. For example, there is a significant body of evidence regarding use of RAGT in stroke patients.

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Despite some lack of clarity, the best evidence suggests RAGT improves stroke patient’s chance of independent mobility if delivered within the first 3 months after injury.

Most reviews did not draw conclusions regarding the long-term efficacy of RAGT. One study was able to show that positive effects last for young people with CP up to 3 months post intervention. However these results are not conclusive.

There is some evidence that RAGT could be more effective for people with more significant impairment. Reviews often discuss the specific benefits of robotic exoskeleton assistance for people who cannot walk independently. However these results are not conclusive.

Studies were generally unable to establish appropriate dosage. However, treatment frequency and duration was generally 2 – 5 times per week for 30 – 45 minutes.

Lokomat is considered safe. There is a record of adverse events those these are typically minor bruising or muscle pain.

For detailed consideration of efficacy, refer to individual sections in 4. Evidence for different conditions.

Lokomat therapy

Robot assisted gait training

There are two main distinctions separating different types of RAGT device. Devices can be stationary or ambulatory, meaning the device is either fixed (usually to a treadmill) or unfixed. Unfixed, ambulatory devices allow users to walk around in more typical ways and perform different activities such as sitting or squatting. Stationary RAGT devices are further divided between exoskeleton and end-effector type devices. Users of stationary exoskeleton devices wear a lower limb exoskeleton. Users of end-effector devices have robotic ‘arms’ attached to their feet to move their lower limb on preestablished paths. The Lokomat is a model of stationary exoskeleton RAGT device (Bessler et al, 2020).

Exoskeleton-type devices are more common in the literature than end-effector type devices (Calabro et al, 2021b; Bowman et al, 2021). Lokomat is the most common type of stationary exoskeleton RAGT device (Calafiore et al, 2022; Llamos-Ramos et al, 2022; Calabro et al, 2021b; Cumplido et al, 2021). For example, in a review from Calabro et al (2021), all stationary exoskeleton studies (13 in total) used the Lokomat. In a review from Carvalho et al (2017), nine out of 10 studies used the Lokomat.

Only one systematic review found compared use of Lokomat with other RAGT devices (Zhang et al, 2022). Most reviews suggest that there is insufficient data to directly compare the effectiveness of different RAGT devices (Name et al, 2017; Hayes et al, 2018; Llamos-Ramos et al, 2022).

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Dosage

Calabrò et al (2021a) note that there is no consensus on protocols for treatment of people lower limb motor function in people with stroke. Timing, frequency, training session duration and the characteristics of those who could benefit are still disputed. Mehrholz et al (2020) were also unable to determine dosage for people with symptoms of stroke. Where reviews for other conditions attempted to establish dosage, most were unable (Bowman et al, 2021; Cumplido et al, 2021). Carvalho et al (2017) find benefits in young people with CP where frequency of training was at least 4 days per week with a duration of at least 30 minutes. Across all reviews, sessions frequency was usually 30-45 minutes for 2 – 5 times per week.

Time after injury

Clinical practice guidelines for treatment of people with stroke, SCI or TBI suggest that RAGT should not be offered to improve walking speed or distance in ambulatory patients after 6 months since the injury occurred (Hornby et al, 2020). Mehrholz et al (2020) found some evidence suggesting effect was greater for patients who receive treatment within 3 months of injury. Nam et al (2017) found some evidence of improvement in patients with SCI even at 1 year post-injury.

Evidence for different conditions

Spinal cord injury

Six systematic reviews between 2019 and 2022 have examined the use of RAGT by people with SCI. All reviews report limitations including heterogeneity of study designs and treatment protocols which make summarising effects difficult (Zhang et al, 2022). Nam et al (2017) reviewed 10 studies describing a total of 502 people with incomplete spinal cord injury with the aim of assessing the effects of RAGT on improvement in walking related functional outcomes. They found mobility-related outcomes (walking distance, lower limb strength, functional mobility and independence) improved to a greater extent with RAGT compared to typical over-ground training for people who received treatment within 6 months of their spinal cord injury. For people who received RAGT at least one year after their injury, treatment improved gait speed and balance compared to no treatment, but no difference was found for improvements in gait distance, leg strength or functional mobility and independence when compared with over-ground training. Hayes et al (2018) reviewed 12 studies describing a total of 512 participants, 496 with either complete or incomplete SCI and 16 with no injury. The authors found inconsistent evidence around walking speed and walking distance. No evidence reviewed by Hayes et al suggests that use of RAGT can improve walking speed or to a sufficient degree to facilitate community ambulation. The authors conclude that RAGT is likely an effective companion treatment for people with both complete and incomplete SCI when used in conjunction with other therapies.

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Aguirre-Güemez et al (2019) included 20 studies in their systematic review of the efficacy of RAGT on gait, strength and functioning in people with incomplete SCI. Six of those studies, representing 222 participants were included in the meta-analysis. Good quality evidence shows a moderate effect of RAGT on strength, and a large effect on gait and functioning. There was no effect for walking speed.

Fang et al (2020) reviewed 7 RCTs and 11 other studies of varied designs to assess the effects of RAGT on walking ability, spasticity and pain in people with SCI. The authors suggest RAGT can decrease spasticity and improve walking ability but they found no effect on pain. However, results are complicated by separately pooled RCT and non-RCT studies. For example, while results of non-RCTs showed a significant reduction in spasticity after treatment, RCTs did not show the same effect.

Two systematic reviews investigated Lokomat specifically (Alashram et al, 2021; Zhang et al, 2022). Alashram et al (2021) reviewed 16 studies representing 658 people with incomplete SCI. They found the Lokomat may improve gait speed, walking distance, strength, range of motion and mobility. However, the authors suggest Lokomat is no better than over-ground training or bike interventions at improving gait speed. Lokomat combined with conventional physiotherapy may be superior to over-ground training and conventional therapy for improving mobility, walking distance and muscle strength. Alashram et al found insufficient evidence for effects on balance, and non-mobility related outcomes such as depression, cardiorespiratory fitness and quality of life.

Zhang et al (2022) is the only systematic review to compare the effectiveness of Lokomat with other RAGT devices. In this case, the authors compared Lokomat as a stationary RAGT device, with a variety of ambulatory RAGT devices (Ekso, HAL, Indego, REX, ReWalk, and SMA). Most of the participants in the ambulatory RAGT studies had complete SCI, whereas most of the participants in the Lokomat studies had incomplete SCIs. This could suggest benefits of the devices for different populations, however there is insufficient evidence to rely on this judgement. While both types of device improved walking distance, speed and function, the authors conclude that ambulatory RAGT devices are more effective than Lokomat in stimulating muscle activity and may be more cost-effective. Cost-effectiveness was not a targeted outcome of the study and so conclusions regarding this preference for ambulatory RAGT devices should not be relied upon.

Zhang et al is significant as the only review to compare different types of RAGT devices. However there are some quality issues which suggest we should treat the results with caution. For example, the number of studies reviewed is reported differently in different places in the report with no explanation.

Stroke

Use of RAGT technology for stroke patients is growing and a significant body of research investigates the use of RAGT for people who have experienced stroke. Calabrò et al (2021a) note a discrepancy between the implementation of RAGT for stroke patients and the research that supports this. In contrast, Mehrholz et al (2020; 2021) assert with a high degree of confidence that RAGT in combination with conventional treatment can support stroke patients to walk independently. The weight of evidence so far supports the use of RAGT for stroke patients up to 3 months after injury.

Evidence does not so far support the use of RAGT for patients in the chronic stage of stroke (Calabrò et al, 2021a; Hornby et al, 2020; Mehrholz et al, 2020). However, evidence is emerging for the use of RAGT in combination with conventional therapy for patients in the acute or sub-acute stages of injury. Calabrò et al (2021a) note evidence that RAGT can improve chances of independent gait in people with more severe impairments and in early stages of recovery, especially when combined with other treatments. From a review of 13 papers, Baroncheli et al (2021) produced positive results for improvements in balance after treatment using Lokomat. The largest review to date (Mehrholz et al, 2020; Mehrholz et al, 2021), including 62 studies and 2440 patients, found with a high degree of confidence that patients who receive RAGT in combination with conventional treatment are more likely to achieve independent walking than patients who receive gait training without the robotic device. They also note less certain evidence that the effect is more pronounced for people who receive treatment within 3 months of injury.

However, other reviews provide more mixed evidence. Lorusso et al (2022) focus on ambulatory RAGT device (not Lokomat) and find that use of these devices does not improve balance or activities of daily living more than conventional treatment. Nedergård et al (2021) found mixed results of low certainty in a review of 13 papers investigating the effect of RAGT on biomechanical measures of gait. They found no significant difference from conventional therapy for gait speed, cadence, spatial asymmetry and step length on the non-affected side. There were slight improvements over conventional therapy for stride length, step length on the affected side and temporal asymmetry calculated in ratio values. Calafiore et al (2022) show that while RAGT combined with conventional treatment can be effective in improving gait for people who have experienced stroke within 6 months, it has not been demonstrated that it is superior to conventional treatment alone. Only one out of the 9 Lokomat RCTs that Calafiore et al reviewed showed a significant improvement of RAGT with conventional treatment compared to conventional treatment alone. Three RCTs showed superiority of conventional treatment compared with RAGT alone and six RCTs showed no significant difference between RAGT combined with conventional treatment and conventional treatment alone.

The discrepancy between Nedergård et al (2021) and Calafiore et al (2022) on the one hand, and the more comprehensive study from Mehrholz et al (2020; 2021) could be related to smaller samples and lower quality studies for Nedergård et al and Calafiore et al. It could also relate to failure to separate out sub-groups (ambulatory, non-ambulatory) or differing Lokomat therapy

Research paper

Multiple Sclerosis

Five systematic reviews between 2019 and 2022 have examined the use of RAGT by people with MS. Sattelmayer et al (2019) found walking speed and level of disability (as measured by did the Expanded Disability Status Scale) were slightly but not significantly improved in RAGT compared to conventional overground walking therapy. The authors emphasise that their meta-analysis is compatible with no real difference in effect between RAGT and conventional therapy. Yeh et al (2020) found RAGT was comparable to conventional walking therapy in improving walking performance, quality of life, pain and activities of daily living. RAGT was found to be superior to conventional treatment in improving perceived fatigue, spasticity and global mobility. Bowman et al (2021) found RAGT was superior to unspecific balance and gait intervention but showed similar improvements in balance, gait speed, walking ability, and stride length when compared to specific rehabilitation training programs like conventional walking training or sensory integration balance training. Sattelmayer et al (2019) were unable to determine whether effects of RAGT depend on severity of symptoms of MS (as measured by EDSS). More recently, Calabrò et al (2021b) found RAGT was superior to other treatments in improving non-motor outcomes such as spasticity, fatigue, pain, psychological well-being and quality of life and comparable to conventional treatment for gait and mobility for users with mild to moderate symptoms of MS. However, they also found RAGT is more effective for people with more severe symptoms (EDSS 6-7.5) compared to conventional treatment. This is further supported by Binshalan et al (2022), who found RAGT is more effective for people with severe MS compared to conventional treatment. They found that RAGT had the most supporting evidence of all physiotherapy interventions considered for this cohort. The authors did not distinguish models of RAGT devices in their review. They found statistically significant improvements in the 6 minute walk test, 10 metre walk test, Berg Balance Scale and Fatigue Severity Scale. They found no significant results on the Timed Up and Go test. Binshalan et al interpret the results on these outcome measures as suggesting RAGT can improve aerobic capacity, endurance and walking speed for people with severe MS. They also suggest RAGT is unlikely to improve capacity to transfer or sit-to-stand in people with severe MS, and therefore RAGT should be supplemented with other physiotherapy interventions. However, the authors also note that there is little evidence for the effectiveness of other physiotherapy interventions on mobility in people with severe MS.

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Parkinson’s Disease

There is evidence that RAGT can improve gait and motor skills in people with Parkinson’s disease, though it is not clear whether RAGT is better than conventional therapy.

Alwadat and Etoon (2019) reviewed three case studies and an uncontrolled pilot study with a combined population of 26. The case studies all used the Lokomat. The pilot study did not report the type of RAGT device used. The authors found RAGT improves freezing of gait in people with Parkinson’s disease. However, the authors note quality issues and low level of evidence from the included studies.

Alwadat et al (2018) reviewed 7 randomly controlled trials investigating the effectiveness of RAGT on motor impairments in people with Parkinson’s Disease. Only two of the 7 studies used the Lokomat with a combined total of 68 subjects. Both Lokomat studies showed significant improvement in outcomes measure for RAGT compared to the regular exercise. However, they showed improvement in different measures. One study showed significant improvement in the 10-metre walk test (10mWT) and Unified Parkinson Disease Rating Scale Part III (UPDRS-III). The other did not show improvement in UPDRS-III but did show improvement in 10mWT and the Timed Up and Go (TUG) test.

Across all seven studies, RAGT was significantly better than regular exercise or treadmill training according to UPDS-III, Berg Balance Scale, 10mWT, and stride length. Significant results were not found for TUG, stride time, cadence, or Activities-Specific Balance Confidence scale. In sum, the authors conclude that RAGT can improve some gait and motor skills but that it was not shown to be superior to regular physiotherapy intervention for improving motor skills in people with Parkinson’s disease.

Cerebral Palsy

Six systematic reviews between 2017 and 2022 have examined the efficacy of RAGT for people with CP. Three of the reviews only considered children and adolescents by design (Llamos-Ramos, 2022; Olmos-Gómez, 2021; Cumplido et al, 2021). Of the other three systematic reviews, the majority of participants in the majority of studies were under 18 years. Volpini et al (2022) reviews only one study with participants aged up to 19 years. Conner et al (2022) reviews one study with participants aged 15 - 35, though the other seven reviewed papers included only participants under 18 years. Carvalho et al (2017) reviews studies for participants up to the age of 21. The results reported below are likely only valid for children and adolescents and caution should be used applying them to older adult populations.

One of the first reviews of RAGT for people with CP(Carvalho et al, 2017) found suggestive evidence that RAGT could improve gait speed, endurance and gross motor function in children and young adults with CP. Benefits were found in studies where frequency of training was at least 4 days per week with a duration of at least 30 minutes. Studies which divided participants by GMFCS classification provided some evidence that RAGT is of greater benefit to people with lower GMFCS classifications (I – II) than higher (III – IV). However, due to low levels of

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The evidence and significant heterogeneity in sample characteristics (e.g., wide variation in GMFCS classification) mean that authors’ generalizations are not wholly reliable.

Meta-analyses by Olmos-Gomez et al. (2020) and Conner et al. (2022) found RAGT offers no improvement over standard care based on their reviews of RCTs. Olmos-Gomez (2020) reviewed eight studies with a combined population of 217 subjects, finding no difference between RAGT and conventional physiotherapy or for RAGT combined with physiotherapy alone in dimensions D and E of the GMFM, gait speed, resistance, and step length. Conner et al. (2022) reviewed eight studies with a combined population of 188 subjects, finding no improvement above conventional treatment according to the 6mWT, walking speed or GMFM dimensions D and E. They also found that RAGT using the Lokomat was not more effective than conventional physiotherapy treatment.

Both reviews cautioned that their meta-analyses results may not generalize due to heterogeneous presentation of CP and differences in comparison interventions.

Llamos-Ramos (2022) and Cumplido et al. (2021) found inconsistent evidence, with studies showing variously no benefit, significant benefit compared to conventional treatment or equal benefit compared to conventional treatment. Llamos-Ramos concludes that while evidence does not support the use of RAGT alone, it is likely a useful tool to complement other therapies for children with CP. Cumplido et al. (2021) agree that there is suggestive evidence of some benefit from RAGT but emphasize that positive results may not generalize as most studies represented low levels of evidence and considered different types of RAGT devices together, often mixed with other interventions such as conventional walking training and virtual reality devices.

Volpini et al. (2022) is the first study to review maintenance of effects of RAGT over the long term, defined as 3 months after treatment. They found that RAGT improves walking distance in the short term and these benefits were maintained in the long term. They also found clinically but not statistically significant improvements in gait speed and gross motor function which were also maintained in the long term. However, it should be noted that most studies reviewed had a high risk of bias and the meta-analysis considered only 77 subjects. Also, few studies reported on how the long-term follow-up was controlled or whether subjects continued using RAGT or received other therapies during follow-up.

Risks and contraindications

Injuries have been associated with use of RAGT devices. Bessler et al. (2020) reviewed 50 studies of RAGT devices, finding that out of these, 27 studies including 489 subjects investigated the Lokomat and reported 12 adverse events. Types of adverse events included muscle pain, joint pain, skin erythema, open skin lesions, skin abrasions, tendinopathy, discomfort, redness, giddiness, bruises, fear of device, skin irritation, proximal tibial fracture, and atypical autonomic dysreflexia. On average, there were 16.6 occurrences of adverse events per 100 subjects.

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The majority of adverse events were minor soft-tissue (muscle pain, bruising, skin lesions) or musculoskeletal injuries. Cumplido et al (2021) suggest RAGT is safe for children with CP. Their review found no reports of adverse events.

According to the manufacturer (Legal Notes, 2016), the following risk factors should lead to additional safety measures or may indicate that use of the Lokomat is not appropriate:

arthroplasty (especially hip arthroplasty or arthroplasties where external hip rotation is contraindicated for the patient)
uncontrolled hip, knee or ankle instability that would still pose a danger despite the body weight support (especially lateral instability when training with the FreeD module).
lack of head control
joint contractures or limitations in the range of motion due to spasticity that can’t be reduced
differences in leg length correctable with an insole
skin lesions (including pressure sores) in areas of contact with harness support, robotic orthosis (buttocks and along lower extremities) or lower extremity loading (feet).
sensory impairment in the lower limbs and trunk, especially reduced pain sensation
risk of autonomic dysreflexia (level at or above T6; history of AD increases the risk of having a reoccurring episode)
recent history or elevated risk of seizures
cardiac conditions, e.g., cardiac insufficiency and thoracotomy, uncontrolled orthostatic hypotension or other circulatory problems, vascular disorders of the lower limbs
uncooperative or (self-)aggressive behaviour (e.g., transitory psychotic syndrome)
mechanical ventilation
long-term infusions (e.g., baclofen pump, intrathecal pumps, PEG tube…) or stimulators (e.g. pacemakers, nerve stimulators).

A person should not use Lokomat if they:

have, have had, or can be suspected of having significantly reduced bone density loss or increased risk of fractures
are heavier than 135kg, lighter than 10kg or taller than 2m

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have an upper leg length of less than 21 cm or more than 35 cm for the paediatric orthosis or less than 35 cm and more than 47 cm for the adult orthosis
have non-consolidated bone fracture
fixed joint contractures that limit the range of motion of the orthosis
any condition that prevents proper and pain-free adjustment of the harness or orthosis (e.g. pregnancy, colostomy bag, unprotected skin lesions, uncorrectable difference in leg length)
any condition preventing active rehabilitation (e.g. respiratory disease, pregnancy, orthopedic conditions, cognitive deficits limiting communication, neuro-psychological conditions, infections or inflammatory disorders, osteomyelitis).

References

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Calafiore, D., Negrini, F., Tottoli, N., Ferraro, F., Ozyemisci-Taskiran, O., & de Sire, A. (2022). Efficacy of robotic exoskeleton for gait rehabilitation in patients with subacute stroke: a systematic review. European Journal of Physical and Rehabilitation Medicine, 58(1), 1–8. https://doi.org/10.23736/S1973-9087.21.06846-5
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Cumplido, C., Delgado, E., Ramos, J., Puyuelo, G., Garcés, E., Destarac, M. A., Plaza, A., Hernández, M., Gutiérrez, A., & García, E. (2021). Gait-assisted exoskeletons for children with cerebral palsy or spinal muscular atrophy: A systematic review. NeuroRehabilitation, 49(3), 333–348. https://doi.org/10.3233/NRE-210135

Fang, C.-Y., Tsai, J.-L., Li, G.-S., Lien, A. S.-Y., & Chang, Y.-J. (2020). Effects of robot-assisted gait training in individuals with spinal cord injury: A meta-analysis. BioMed Research International, 2020, 2102785. https://doi.org/10.1155/2020/2102785

Hayes, S. C., James Wilcox, C. R., Forbes White, H. S., & Vanicek, N. (2018). The effects of robot-assisted gait training on temporal-spatial characteristics of people with spinal cord injuries: A systematic review. The Journal of Spinal Cord Medicine, 41(5), 529–543. https://doi.org/10.1080/10790268.2018.1426236

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Lokomat Therapy and robot assisted gait training

Lokomat Therapy and robot assisted gait training

Research paper

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Contents

Summary

Research paper

Lokomat therapy

Robot assisted gait training

Research paper

Dosage

Time after injury

Evidence for different conditions

Spinal cord injury

Research paper

Stroke

Research paper

Multiple Sclerosis

Parkinson’s Disease

Cerebral Palsy

Research paper

Risks and contraindications

Research paper

Research paper

References

Research paper

OFFICIAL For Internal Use Only

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