INTRODUCTION
Cerebral palsy (CP) is a neurodevelopmental disorder caused by brain damage during early development, clinically manifested by postural and motor dysfunction [1]. Sensory, perceptual, cognitive and communication deficits, as well as behavioral problems, epilepsy and secondary musculoskeletal problems, often accompany this CP-related motor dysfunction. CP exhibits clinical features that fall into four categories: spastic, irregular, atactic, or mixed [1]. The prevalence of CP ranges from 0.20 to 0.35% among living infants. In 2023, the number of people with CP reached 17 million worldwide [1]. About 40% of these patients cannot walk independently, significantly affecting their daily functioning [2]. Clinical rehabilitation interventions for CP patients mainly include neurodevelopmental therapy, physiotherapy and hydrotherapy, which succeeded but they are less effective in treating gait and balance functions [2].
Robot-assisted gait training (RAGT) is a new rehabilitation intervention that facilitates repetitive and effective gait training with external mechanical support [3]. In patients with crouch gait, the robotic exoskeleton has improved knee range of motion in patients with spastic cerebral palsy [4]. Training on a robot-assisted treadmill significantly improved in standing and walking function [5].
The studies are still few, outcome measures and treatment effects vary, clinical effectiveness remains controversial, and more high-quality evidence-based medicine is needed to support this [6]. Meta-analysis is a statistical method that quantifies several interventions and prioritizes the effects of interventions based on different outcome measures. In this study, we used the meta-analysis method to search for RAGT studies for patients with CP, extract relevant outcome measures to assess their effectiveness, and provide evidence-based references for the clinical application of RAGT training.
Material and methods
This study was registered on the PROSPERO platform CRD4202346954. The search time window lasted from 6.10.2023 to 4.11.2023. Three reviewers conducted the main search independently (A.K., M.D., M.M.).
Search strategy
The authors conducted a meta-analysis after a systematic search of all relevant articles in Med of Science, Cochrane, PubMed, Science, EBSCO, and Embase databases (Supplementary File) with a limitation of the search by language-only English-language publications, a range of 10 years and only publications published as articles or book chapters based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was conducted from 2013 to 2023. Three independent reviewers conducted the leading search, and keywords included:
- — 1# “Cerebral palsy” OR “cerebral paralysis” OR “spastic cerebral paralysis” OR “monoplegic cerebral palsy” OR “diplegic cerebral palsy” OR “hemiplegic cerebral palsy” OR “tetraplegic cerebral palsy”.
- — 2# “Robot-assisted gait therapy” OR “Robotic gait rehabilitation” OR “exoskeleton” OR “HAL” OR “trexo” OR “Lokomat” OR “ekso” OR “RoboGait” OR “wearable robot”.
- — 1# AND 2#.
The condition was limited to studies measuring GMFM, UP& GO and 6MWT. After completing the search, the results were checked, and, in case of discrepancies, the decision was discussed with a third researcher (Fig. 1).
Three reviewers screened and independently checked the titles and abstracts (AK, MD, MM). After combining studies from six databases and removing duplicates, we obtained texts of potentially relevant articles. Three independent reviewers evaluated each article for eligibility based on the purpose of the study. Articles were included based on the following:
- — population (people with CP);
- — Gross Motor Function Classification System (GMFCS) I–IV;
- — type of intervention (robot-assisted gait training with or without other rehabilitation);
- — outcomes (GMFM, 6MWT, UP&GO).
Any discrepancies were assessed and resolved by discussion among three reviewers. We collected relevant data from each study included in the analysis using a standard data recording form. The form included details such as publication title, authors and year. Further information collected included the number and age of participants, the intervention protocol (including intervention duration, comparators, number of sessions and any additional interventions), and outcome measures and results (mean and standard deviation). After extraction, studies were excluded if they included non-CP populations, did not include a mean score and standard deviation for 6MWT, UP& GO and GMFM, and had fewer than five patients.
Assessing the risk of bias
Three review authors (A.K., M.D., M.M.) independently assessed the risk of bias using the Risk Of Bias In Non-Randomized Studies 1 (ROBINS 1). The discussion between the three reviewers resolved any disagreements. The following areas were evaluated: bias due to confounding, bias in selecting participants for the study, bias in intervention classification, bias due to deviations from the intended intervention, bias due to missing data, bias in reported results selection, and overall risk of bias. Each area was addressed and labeled: low, moderate and serious. For randomized trials, RoB 2 was used. The following areas were assessed: bias arising from the randomization process, bias due to deviations from the intended intervention, bias due to missing outcome data, bias in the measurement of the outcome, and bias in the selection of the reported result. The answers are the same as in ROBINS 1; each domain was answered: low, moderate and severe (Fig. 2) [7, 8].
Data analysis
Several comparisons of the collected results were made: comparison 1 - the effects of robot-assisted gait training alone compared to the conditions of robot-assisted training and conventional rehabilitation; comparison 2 - the maintenance of the effects of robot-assisted gait training in randomized trials compared to the effects in non-randomized trials. The comparisons included results such as gait distance in the 6MWT, gait speed in the UP & GO test, and GMFM functional test score in domains D (standing) and E (walking, running and jumping).
The mean difference (MD) was chosen as the effect size metric for this meta-analysis. The results were presented as MD, with a 95% confidence interval (95% CI). To account for potential heterogeneity, a random effects model was employed. A random effects model was employed to account for potential heterogeneity. The I2 index, also known as the inconsistency index, was used to quantify the proportion of total variation across studies due to heterogeneity rather than chance. The publication bias was assessed with funnel plots and the Egger’s test. Additionally, sub-analyses were conducted based on whether the study was observational or randomized, as well as whether physiotherapy was administered solely by a robot or with the support of a physiotherapist.
The statistical analysis was performed using Rstudio version 2023.06.0 (2009–2023 posit software) using R-4.2.2 software incorporating packages readxl, ggplot2, meta, and robvis. All tests were significant at p < 0.05 except Cochran’s Q statistic. Given its low power, heterogeneity was deemed significant if p < 0.10.
Results
Studies selection
We identified 892 articles using an electronic search strategy during this systematic review. A cross-analysis of 17 full texts using a standardized data entry form that included outcome measures followed the identification process. The cross-analysis verified exclusion criteria and facilitated data extraction.
Figure 1 shows a detailed study of our qualitative analysis after extracting eligible studies. Seventeen articles in this systematic review and meta-analysis covered 464 people with cerebral palsy. These studies examined the effects of RAGT through assessments such as the 6MWT, the UP&GO test and the measurement of GMFM.
Qualitative analysis
Study quality was assessed based on risk of bias using the ROBINS 1 tool for non-randomized trials and Risk of Bias 2 (RoB 2) for randomized trials. Figure 2 shows the results.
Study quality assessment classifies randomized trials of four [9–12] as low risk and three [16–15] as medium risk. Among the non-randomized studies, eight studies [16–23] were rated as low risk and two papers [24, 25] as medium risk.
Quantitative analysis
The meta-analyses included 17 studies. Ten studies analyzed gait speed using the 6MWT (10,11,13,15,16,19–21,26,27)a controlled force was applied to the pelvis and legs during treadmill walking. For participants who were assigned to the treadmill only group, manual assistance was provided as needed. Each participant trained 3 times/wk for 6 wks. Outcome measures included walking speed, 6-min walking distance, and clinical assessment of motor function, which were evaluated before, after training, and 8 wks after the end of training, and were compared between two groups. Results Significant increases in walking speed and 6-min walking distance were observed after robotic training (P = 0.03. Ten articles analyzed the GMFM total [9, 12, 15, 17, 18, 21, 23, 25], and the D and E dimensions of the GMFM were presented in eight papers [9, 10, 12, 13, 15, 17, 19, 23]. The meta-analysis results for all variables are shown in Figures 3–6, respectively. For 6MTW, the publications discussed the results; the vast majority achieved improvements; the vast majority achieved improvements, but the meta-analysis shows a high degree of heterogeneity. When considering randomized and non-randomized trials separately, a decrease in heterogeneity is in the non-randomized group. According to the publication groups with RAGT alone and RAGT with conventional rehabilitation, heterogeneity shows only low levels in the RAGT alone group. Observers reported significant improvements in functional status when using the GMFM scale for functional assessment. There was minimal variation in the results of each analysis, regardless of whether randomized or non-randomized trials were considered. The same was true for publications describing RAGT alone or RAGT with conventional therapy. We observe average heterogeneity in the total works analyzed in the D and E dimensions of the GMFM scale.
Discussion
This systematic review aimed to provide a comprehensive overview of RAGT therapy’s effectiveness in increasing total gait distance and functional status among people with CP at different levels of the GMFCS. The results showed that RAGT led to an increase in total gait distance as measured by 6MWT and improved functional abilities as assessed by the measurement of GMFM. The systematic review found a positive clinical effect for gait speed and GMFM total in the D and E dimensions. These findings align with results from other studies that specifically assessed the short-term effects of RAGT [27–29]. The observed lack of statistically significant differences may be due to the sample size. The literature shows that meter increments of 20, 50 meters in 6MTW are rated as small to medium effects in the adult population [30]. Therefore, when the meta-analysis showed a mean improvement of 29.65m, the results of 6MWT should be considered clinically non-significant. Improvements in GMFM may indicate that RAGT has the potential to generate greater independence and functionality for these individuals. A study by van Hedel et al. found that the more significantly reduced a child’s walking ability (GMFCS IV), the greater the benefit gained from RAGT, including improvements in physical and cardiorespiratory fitness [19].
Currently, no objective data are available regarding the optimal RAGT protocol. Larger controlled studies are required to determine the optimal timing and protocol design that will maximize efficacy and long-term outcomes in cerebral palsy patients. Another important issue is the availability and cost of these devices. At present, their usage is limited to highly specialized centers with the required space and resources. Therefore, more compact and affordable devices for home use are needed.
Conclusions
Evidence from this systematic review with meta-analysis showed that RAGT can clinically improve balance, gait distance, and function in people with CP. The results show that both 6MWT and GMFM improve after the therapies. Therefore, RAGT is a valid intervention to benefit balance, gait distance, walking distance and functional ability in people with CP. Our findings reinforce the importance and need for more randomized clinical trials that examine outcome maintenance.
Acknowledgements
Most appreciation goes to the team that searched databases and analyzed articles that qualified for systematic review.
Author contributions
A.KK.: designed the study, conducted database searches, then analysis, prepared data for processing by a statistician and wrote the manuscript with support from M.D., M.M., M.M., M.J. M.D.: conducted database searches, then analyzed and prepared data for processing by a statistician. M.M.: conducted database searches, then analyzed and prepared data for processing by a statistician. M.M.: made statistical calculations and performed advisory functions. M.J.: supervised the findings of this work.
Conflict of interest
The authors report no conflicts of interest.
Funding
The work was done as part of scientific development without financial support.
