Accepted Manuscript

Robotic Gait Training For Indiviuals With Cerebral Palsy: A Systematic Review And
Meta-Analysis

Igor da Silveira Carvalho, Srgio Medeiros Pinto, Daniel das Virgens Chagas, Jomilto
Luiz Praxedes dos Santos, Tain de Sousa Oliveira, Luiz Alberto Batista

PII: S0003-9993(17)30474-4
DOI: 10.1016/j.apmr.2017.06.018
Reference: YAPMR 56958

To appear in: ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION

Received Date: 11 May 2017

Revised Date: 17 June 2017
Accepted Date: 19 June 2017

Please cite this article as: da Silveira Carvalho I, Pinto SM, Chagas DdV, Praxedes dos Santos JL, de
Sousa Oliveira T, Batista LA, Robotic Gait Training For Indiviuals With Cerebral Palsy: A Systematic
Review And Meta-Analysis, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2017), doi:
10.1016/j.apmr.2017.06.018.

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 ACCEPTED MANUSCRIPT
Running Head: Robotic Gait Training

Title: Robotic Gait Training For Indiviuals With Cerebral Palsy: A Systematic Review

And Meta-Analysis

Authors: Igor da Silveira Carvalho1, Srgio Medeiros Pinto1, Daniel das Virgens

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Chagas2, Jomilto Luiz Praxedes dos Santos2, Tain de Sousa Oliveira3, Luiz Alberto

Batista4

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1. MSc, Laboratory of Biomechanics and Motor Behavior, Graduate Program in

Medical Sciences - Rio de Janeiro State University (UERJ). Rio de Janeiro, Brazil.

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2. PhD, Laboratory of Biomechanics and Motor Behavior, Institute of Physical
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Education and Sports - Rio de Janeiro State University (UERJ). Rio de Janeiro, Brazil.

3. Laboratory of Biomechanics and Motor Behavior, Institute of Physical Education

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and Sports - Rio de Janeiro State University (UERJ). Rio de Janeiro, Brazil.
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4. Associate professor, Laboratory of Biomechanics and Motor Behavior, Institute of

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Physical Education and Sports - Rio de Janeiro State University (UERJ). Rio de

Janeiro, Brazil. Graduate Program in Medical Sciences - Rio de Janeiro State

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University (UERJ). Rio de Janeiro, Brazil.

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Conflicts of interest: Nothing to disclose.

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Acknowledgements

The first author is supported by the National Counsel of Technological and Scientific

Development (CNPq).
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Corresponding Author: Igor da Silveira Carvalho, Laboratory of Biomechanics and

Motor Behavior, Institute of Physical Education and Sports - Rio de Janeiro State

University (UERJ). E-mail: igorscarvalho0@gmail.com

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1 Robotic Gait Training for Individuals with Cerebral Palsy: A Systematic Review

2 and Meta-Analysis

4 Abstract

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6 Objective: To identify the effects of robotic gait training practices in individuals with

7 cerebral palsy.

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8

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9 Data Sources: The search was performed in the following electronic databases:

10 PubMed, EMBASE (Excerpta Medical), MEDLINE (OvidSP), CDSR (Cochrane

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database of systematic reviews), Web of Science, Scopus, Compendex, IEEE Xplore,
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12 ScienceDirect, Academic Search Premier, and PEDro.

13
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14 Study Selection: Studies were included if they fulfilled the following criteria: (1) they
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15 investigated the effects of robotic gait training, (2) they involved patients with cerebral
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16 palsy, and (3) they enrolled patients classified between levels I and IV using the Gross

17 Motor Function Classification System.

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18

19 Data Extraction: The information was extracted from the selected articles using the
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20 descriptive-analytical method. The "Critical Review Form for Quantitative Studies" was
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21 used to quantitate the presence of critical components in the articles. To perform the

22 meta-analysis, the effects of the intervention were quantified by effect size (Cohen's

23 d).

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25 Data Synthesis: Of the 133 identified studies, 10 met the inclusion criteria. The meta-

26 analysis showed positive effects on gait speed (0.21 [-0.09, 0.51]), endurance (0.21 [-
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27 0.06, 0.49]), and gross motor function in dimension D (0.18 [-0.10, 0.45]) and

28 dimension E (0.12 [- 0.15, 0.40]).

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30 Conclusion: The results obtained suggest that this training benefits people with

31 cerebral palsy, specifically by increasing walking speed and endurance and improving

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32 gross motor functions. For future studies, we suggest investigating device

33 configuration parameters and conducting a large number of randomized controlled

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34 trials with larger sample sizes and individuals with homogeneous impairment.

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35

36 Keywords: robotic training; gait; cerebral palsy; systematic review; meta-analysis.

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38 Abbreviations:

39 CP: Cerebral Palsy

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40 PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses

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41 GMFM: Gross Motor Function Measure Dimension

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42 OCEBM: Oxford Centre for Evidence-based Medicine

43 ICF: International Classification of Functioning, Disability and Health

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44 WHO: World Health Organization

45 GMFCS: Gross Motor Function Classification System

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46 10mWT: 10 meter Walk Test

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47 6minWT: six minute Walk Test

48 FAC: Functional Ambulation Categories

49 GTI: Gait Trainer I

50 MCID: Minimal Clinically Important Difference

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52
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53 Introduction

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55 Cerebral palsy (CP) is the most common cause of physical disability in childhood.1,2 It

56 consists of a group of disorders in motor and postural development that result in

57 significant motor limitations for the individual. It is classified as a disease of a

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58 neurological nature and is caused by a non-progressive disorder that affects the brain

59 during fetal development and likely persists through childhood.3

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60

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61 Motor impairments induced by CP are characterized, in part, by the reduced ability to

62 generate strength in certain muscles, resulting in weakness, spasticity, contractures,4

63 and fatigue.5,6
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64

65 For the patient, CP results in significant anatomical and functional changes such as a
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66 reduced range of motion,7 shortening of muscle length,8 muscle weakness,9,10 and

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67 changes in the posture of body segments. An example of this is equinus foot, which is
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68 a condition characterized by the heel being kept high during ambulation, which in turn

69 changes the initial contact of the feet on the ground.11

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70

71 Furthermore, CP affects selective muscle control and muscle synergism, which is a

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72 decisive event in coordination required in the performance of motor skills.12

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73

74 Gait is commonly affected by CP; therefore, people affected tend to have typical

75 changes in body movement pattern. These changes are primarily characterized by a

76 reduction in the magnitude of the displacement velocity13 and stride length.9,14

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78 Changes such as these significantly impair the physical quality of the gait and are

79 associated with the occurrence of undesirable events such as increased instability

80 during ambulation15 and pain,5,6 ultimately leading to a diminished quality of life. Thus,

81 the main goal of rehabilitation programs is to enable and/or restore motor function and

82 promote higher degrees of efficiency and independence in the individual.16,17

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83

84 Scientific evidence suggests that functional therapies, characterized by significantly

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85 similar movements to the motor skills to be enabled or rehabilitated, are effective in

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86 improving a patients motor function.18,19

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Thus, different therapeutic resources emphasizing repetitive movements have been
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89 designed and incorporated into gait treatment programs for individuals with

90 neurological impairment. In this context, the use of robotic devices to facilitate

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91 practicing specific repetitive body movements has provided promising results.20,21

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92
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93 Similar to other therapeutic approaches, the availability of evidence that supports the

94 use of robotic devices is crucial to design the therapeutic process. The

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95 systematization of knowledge produced on the subject is an effective and necessary

96 strategy because it organizes information in a way that facilitates the development of

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97 evidence-based clinical guidelines.22,23

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98

99 The aim of this study was to identify the effects of robotic gait training practices in

100 individuals with cerebral palsy.

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104 Methods

105 This systematic review was conducted according to Preferred Reporting Items for

106 Systematic Reviews and Meta-Analyses (PRISMA) guidelines.22,23 The study did not

107 require ethical approval.

108

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109 Search Strategy

110

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111 The systematic literature search was restricted to full articles that were written in

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112 English, Spanish, or German and published from January 1980 to November 2016.

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114
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The search was performed in the following electronic databases: PubMed, EMBASE
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115 (Excerpta Medical), MEDLINE (OvidSP), CDSR (Cochrane database of systematic

116 reviews), Web of Science, Scopus, Compendex, IEEE Xplore, ScienceDirect,

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117 Academic Search Premier, and PEDro. The terms used in the electronic search were
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118 ''cerebral palsy 'AND' gait 'AND' robot *".

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120 Two researchers (CI and PS or BLA) were responsible for reviewing the titles and
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121 abstracts of the articles found and selecting those that met the inclusion criteria. For

122 the items on which the primary analysts did not reach an agreement, we requested the
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123 opinion of a third reviewer.

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124

125 Inclusion and Exclusion Criteria

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127 Studies were included if they fulfilled the following criteria: (1) they investigated the

128 effects of robotic gait training, (2) they involved patients with cerebral palsy, and (3)
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129 they enrolled patients classified between levels I and IV using the Gross Motor

130 Function Classification System (GMFCS).

131 Articles were excluded from this review if they were case reports and case series

132 studies. Investigations in which any concomitant interventions were used were also

133 excluded.

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134

135 Data Extraction and Quality Appraisal

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136

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137 The "Critical Review Form for Quantitative Studies"24 (Table I) was used to quantitate

138 the presence of critical components in the articles.

139
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140 Table 1: Methodological quality of articles: Critical Review Form for Quantitative

141 Studies.
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142
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143 The information was extracted from the selected articles using the descriptive-
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144 analytical method.25 The collected data included author(s), year of publication,

145 research design, level of evidence, number of participants, participant characteristics,

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146 age (range), intervention, parameters for intervention, outcome measures, dimensions

147 according to the International Classification of Functioning, Disability and Health (ICF),
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148 and results.

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149

150 Statistical Analysis

151 To perform the meta-analysis, the effects of the intervention were quantified by effect

152 size (Cohen's d) and standardized with mean difference and 95% confidence intervals

153 (CI). Heterogeneity was obtained by q Cochran (Q < 1, absence of heterogeneity; Q >

154 1, presence of heterogeneity) and I metric (I <25%, low heterogeneity; I = 25-50%,

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155 moderate heterogeneity; I> 50%, large or extreme heterogeneity). For a negative

156 result, the value is set to zero. The variables used in the meta-analysis were a 10-

157 meter walk test, six-minutes walk test, Gross Motor Function Measure Dimension D

158 (GMFM D), and Gross Motor Function Measure Dimension E (GMFM E). The

159 statistical analysis and graphic visualization were performed using R (http://www.r-

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160 project.org) with the Rcmdr packages and the RcmdrPlugin.MA plugin.

161

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162 Results

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163

164 This systematic review identified 300 articles. After removal of duplicate articles, two

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reviewers independently evaluated 133 titles and found that 75 of these met the
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166 requirements to proceed to the abstract-reading stage. In the abstract-reading stage,

167 30 abstracts were determined by consensus to meet the predetermined manuscript

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168 criteria, which qualified them for the full-text reading stage. The implementation of this
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169 last procedure resulted in the selection of 10 articles that were classified as eligible for
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170 qualitative review (Figure1).

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172 Figure1: PRISMA flow diagram.

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174
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175 To confirm the presence of critical components of methodological quality, the selected

176 articles were evaluated using the "Critical Review Form" (Table 2).

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178 Table 2: Results of methodological quality of articles: Critical Review Form for

179 Quantitative Studies.

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181 0, no; 1, yes; NA, Not applicable.

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183 Concerning the study design, we identified one cohort study, one case-control study,

184 one prospective cohort study, two randomized clinical trials and five before and after

185 studies, which suggest a low level of evidence according to the Oxford Centre for

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186 Evidence-based Medicine (OCEBM).26

187 With regard to patient characteristics, we identified a wide range of age range, from 4

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188 to 22 years. We also found an extensive diversity of motor impairment in the

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189 participants, ranging from levels I to IV on the GMFCS.

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Using the criteria of the ICF proposed by the World Health Organization (WHO), seven
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192 studies investigated individuals with limitations in activity, two studies investigated

193 individuals with limitations in function and activity, and one study investigated
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194 individuals with limited function.

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195
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196 Two gait training devices were used in the studies. The Lokomat (Hocoma,

197 Switzerland) was used in nine studies and the GaitTrainer I (Reha-Stim, Germany)
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198 was used in one study.

199
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200 To identify the effects of training using robotic devices, researchers used different
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201 strategies. Functional tests were used in six studies, with the Gross Motor Function

202 Measure (GMFM) used in dimension D (Standing) and dimension E (Walking,

203 Running, and Jumping). Five studies used the 10-meter Walk Test (10mWT), six

204 studies used the six-minute Walk Test (6minWT), and one study used the Functional

205 Ambulation Categories (FAC)27. Four studies analyzed gait kinematic parameters. The
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206 summaries of study characteristics are presented in two tables, Table 3 for Single

207 Subject Research Designs and Table 4 for Group Research Designs.

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209 Table 3: Summary of study characteristics: Single Subject Research Designs

210 Table 4: Summary of study characteristics: Group Research Designs.

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211

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212 Meta-analysis

213 We performed a meta-analysis of four functional tests, 6minWT (Figure 2), 10mWT

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214 (Figure 3), the GMFM D (Figure 4), and the GMFM E (Figure 5). In the forest plot,

215 studies are arranged in alphabetical order by article title.

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217 The Q Cochran test and I metric showed low heterogeneity between the included
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218 studies. For 6minWT, Q = 0.977 and I = 0, for 10mWT, Q = 0.964 and I = 0, for

219 GMFM D, Q = 1.0 and I = 0, and for GMFM E, Q = 0.998 and I = 0. However, we
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220 chose to use the random-effect model for statistical analysis because the samples
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221 used in the studies included in this review presented important differences with

222 respect to motor impairment.

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223
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224 Discussion
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225 This systematic review aimed to identify the effects of robotic gait training practices in

226 individuals with cerebral palsy.

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228 Level of evidence

229 In evaluating the OCEBM level of evidence of the selected articles, we identified five

230 before and after studies, one prospective cohort, and one case control; these study
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231 design types were classified as level IV. In addition, we found one study cohort design

232 that was classified as level III. Randomized clinical trials were conducted only in two

233 cases; however, because the sample size was less than 100, they only reached the

234 level II classification. This low level of evidence makes it difficult to generalize the

235 results and establish cause and effect relationships.38

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236

237 Samples characteristics

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238 Participants in the selected studies had spastic diplegia, quadriplegia, hemiplegia,

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239 double hemiplegia or ataxia. In the study by Smania et al (2011)35, participants had

240 spastic diplegia and tetraplegia, with GMFCS classification levels between II and IV.

241
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Meyer-Heim et al (2009)29 included subjects with GMFCS levels between II and IV. In
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242 the study by Borggraefe et al (2010, b)30 individuals showed the highest variability in

243 GMFCS levels, which ranged from I to IV.

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244
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245 The range of motor impairment limits this systematic review because the difference
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246 between the categories of GMFCS classification is significant.39 Individuals who are

247 classified as level I are able to walk without the aid of devices but with reduced gait
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248 speed and impaired balance and coordination. Individuals classified at level IV can

249 only walk with assistive devices and short distances.

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250
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251 Robotic devices

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253 In this review, we identified the use of two devices for gait training. The Lokomat was

254 used in nine studies, and the Gait Trainer I (GTI) was used in the remaining one.

255 Although the objective of this study was not to compare the effects of equipment on

256 gait, the fact that there were only two devices necessitates a brief comment.
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257 According to the data provided, the study that used the GTI35 identified statistically

258 significant positive effects by using the device. There were six studies using the

259 Lokomat that identified statistically significant positive results and three studies that

260 obtained positive but not statistically significant results.

261

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262 Unfortunately, these results do not achieve value-establishment about the advantages

263 of one device compared with the other because the difference in equipment training

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264 frequency prevents this type of conclusion.

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265

266 Parameters for intervention

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There are some important parameters to be considered in the design of an exercise
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268 regime and/or motor technique, some of which are inherent to the intervention

269 process.
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270
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271 Eight articles stated the total number of sessions, weekly frequency, and duration of
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272 each session. The studies of Drubicki et al (2013),37 Shroeder et al (2014),33 and

273 Arellano-Martinez (2013)32 did not report the weekly frequency, thus making it difficult
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274 to understand the training volume.

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276 It can be observed in the included studies that the total number of sessions varied
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277 between 10 and 40, the weekly frequency varied between two and five and the

278 training duration varied between 20 and 60 minutes. The optimal level of intensity in

279 intervention programs for cerebral palsy is still being debated,40 and the results of the

280 studies on the subject are dissonant.41,42

281
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282 The weekly frequency analysis of intervention programs used in the studies could not

283 be used to establish a consensus. The data suggest that in general, a weekly

284 frequency of training greater than or equal to four days per week (observed in four

285 studies), results in significantly improved gait speed and endurance and step length.

286 Only one study showed improvements in gait with a training frequency less than four.

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287 This frequency intervention can be classified as intensive because it is greater than

288 three times per week.43 Thus, this finding is in agreement with Tsorlakis et al (2004),42

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289 who found that therapeutic intervention programs with intensive training achieve

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290 significantly higher motor gains than non-intensive training.

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Concerning the duration of training, only two studies proposed training for 20 minutes,
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293 and they did not show satisfactory results. Studies that presented significant positive

294 results proposed training lasting 30 minutes or longer. However, Mehrholz et al

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295 (2007)44 in their systematic review studying the effect of robotic training for stroke
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296 patients did not conclude what duration would be the most effective and suggested
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297 further studies about this training parameter.

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299 Device configuration parameters

300
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301 The device configuration is defined as the possibility of adjusting the equipment
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302 parameters for gait training, such as body weight support, step length, cadence,

303 walking speed, and adjustments in the angular variation of the hip, knee and ankle

304 joints.

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306 Regarding device configuration for gait training, only studies by Arellano-Martinez et al

307 (2013),32 Borggrfe et al (2010),30 and Borggrfe et al (2010b)31 contained information

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308 that would allow the replication of the experiment. It should also be noted that the

309 criteria for the device configuration varied between studies.

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311 It is known that anthropometric variables of an individual influence gait kinematic

312 behavior.45 The studies of Druzbicki et al (2013)37 and Arellano-Martnez et al (2013)32

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313 accounted for the anthropometric measurements of the subjects for the device

314 configuration. Anthropometric variables are related to gait motor behavior and interfere

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315 with the dimensions of the step and stride.46

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316

317 Another study that described device configuration was that by Smania et al (2011).35

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The equipment was adjusted according to the gait parameters collected from
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319 individuals in the pretest. However, in other studies included in this review, it was not

320 possible to identify the criteria that were used to select the device configuration
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321 parameters, thus making it difficult to establish valid standards for scientifically
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322 adequate training using robotic devices.

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323

324 Training effects

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325 In the 10 articles selected for this review, seven studies showed statistically significant

326 positive effects on gait speed and endurance in patients with cerebral palsy.
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327
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328 Seven studies examined gait kinematics. Arellano-Martinez et al (2013)32 identified

329 improvements in the gait speed and the step size by videography. Smania et al

330 (2011)35 showed more appropriate timing in the angular variation of the hip joint during

331 the initial contact, midstance, and initial swing, and they also found an improvement in

332 gait speed and the step size. Corroborating this study, Patritti et al (2009) 47 also

333 observed improvements in the angular variation of the hip.

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334

335 The gait speed was also measured in the 10mWT.28,29,31,34,35 Significant improvement

336 was observed in five studies. Mayer-Heim et al (2007)48 showed an increase in gait

337 speed in patients with neurological damage, including cerebral palsy. This

338 improvement may be related to the increased muscle strength from training.20,49

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339 Although muscle strength was not measured in these studies, in previous studies,

340 subjects reported feeling muscle fatigue after treatment; this suggests that training

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341 with a robotic device produces an active response in lower limb muscles.20 The results

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342 obtained by Gizzi et al (2012)50 reinforce this conclusion because the

343 electromyographic signals obtained in their examination showed that training with a

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robotic device induces muscle activity similar to that of walking.
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345

346 Another possible cause for increased gait speed is modification of the intersegmental
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347 pattern coordination of the lower limbs, as suggested by the data obtained by
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348 Wagenaar and van Emmerik (2000),51 who identified a positive association between
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349 gait speed and intersegmental coordination in healthy individuals, and Meyns et al

350 (2012),52 who undertook a similar study in individuals with cerebral palsy. Krishnan et
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351 al (2012)53 reported improved muscle coordination in stroke patients who underwent

352 robotic gait training.

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353
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354 Individuals affected by cerebral palsy have a higher energy expenditure when walking

355 than non-affected individuals.54-56 Cardiovascular and respiratory ability while walking

356 were measured using the 6minWT, which has been validated for this purpose.57 The

357 variables associated with these skills were measured in six studies; the studies of

358 Borggrfe et al (2007),28 Borggrfe et al (2010b),31 and Smania et al (2011)35 reported

359 an improvement in cardiovascular function, corroborating the study of Mayer-Heim et

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360 al (2007),48 which identified improvement in performance on the 6minWT in individuals

361 with neurological injury, including cerebral palsy. This evidence was reinforced by

362 findings by Turiel et al (2007),58 who suggested that cardiovascular function improves

363 in individuals with spinal cord injury after training, and by Chang et al (2012),59 who

364 found an increased VO2 in patients with subacute stroke.

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365

366 Studies show a positive association between the best performance, characterized by

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367 the greatest distance, and a decrease in energy expenditure to perform the task.60 The

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368 reduction in energy cost may be related to decreased co-contraction of the spastic

369 muscle and a more efficient gait pattern.61,62 This reduction allows greater mobility,

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activity, and participation because the decrease in energy expenditure during walking
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371 is strongly associated with increased GMFM.63

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373 Among the observed effects, changes in gross motor skills were measured by GMFM-
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374 66 for dimensions D and E. In six studies, four showed significant improvements in
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375 both dimensions. The study of Mayer-Heim et al (2009)29 showed improvements only

376 in dimension D. Romei et al (2012)36 did not identify statistically significant

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377 improvements.

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379 A positive correlation was found between the improvement in the score of dimension E
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380 of the GMFM-66, the distance traveled and the time during gait training, which

381 suggests that training has an effect on gait function optimization. 31

382

383 It should be noted that in studies in which the results are stratified by participant

384 GMFCS function, a greater improvement in gross motor function was observed in

385 patients classified as GMFCS I or II than in patients classified as GMFCS III or IV.
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386 These findings are consistent with those of other studies that indicate a lower potential

387 for gains in motor function in GMFCS III and IV subjects. 64

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389 Regarding GMFCS, Veraluce-Rodriguez et al (2014)33 and Arellano-Martnez et al

390 (2013)32 identified changes before and after training. Specifically, patients tended to

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391 improve by one level after training. Therefore, we suggest that in these studies, the

392 participants achieved gains in gross motor function.

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393

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394 The minimum clinically important difference (MCID) is the smallest change that an

395 instrument can detect, making it possible to interpret whether this observed change

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results in improvement or worsening of the individual's symptoms.65,66 Oeffinger et al
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397 (2008)67 identified the MCID in the dimensions D and E of GMFM-66 for individuals

398 with cerebral palsy. Their data point to a large effect size in studies that demonstrate
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399 an increase equal to or greater than 1.8 in dimension D. The articles selected by this
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400 review showed an amplitude in the improvement of gross motor function between 2.7
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401 and 6.3, demonstrating a large effect size in dimension D. With regard to dimension E,

402 Oeffinger et al (2008)67 indicate significant clinical effects; an increase of 1.6 for
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403 medium-effect size and 2.6 for large-effect size. The data obtained in our study shows

404 that all articles selected reached a large effect size when evaluating the E dimension
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405 of GMFM-66.
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406

407 With regard to the tests 10mWT and 6minWT, we identified studies that established

408 the MCID for stroke 68,69 and spinal cord injury70; however, we did not find studies with

409 this information involving individuals with cerebral palsy. This made it infeasible to

410 analyze the results obtained by this review. Therefore, we suggest future studies be
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411 performed to determine the MCID of the respective tests for people with cerebral

412 palsy.

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414 Regarding the meta-analysis, the forest-plot of the variables is shown in different-

415 sized boxes plotted for each of the individual studies. The area of the box representing

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416 the weight that the study takes in the analysis provides a visual representation of the

417 relative contribution that each study makes to the overall effect.71 The area of the

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418 black squares reflects the weight of the study in the meta-analysis. Methods used for

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419 meta-analysis employ a weighted average of the results in which the larger trials

420 generally have more influence than the smaller ones. In practice, the weights are often

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the inverse of the variance of the treatment effect, which relates closely to sample
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422 size.72 The representative diamond shows a positive effect of gait training using

423 robotic devices. However, the confidence intervals indicated a low significance. This
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424 may have occurred because of the small sample sizes. Therefore, future studies with
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425 larger sample sizes and individuals with homogeneous levels of motor impairment
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426 should be conducted.

427
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428 Implications for practice

429 The evidence in this review suggests that, despite the heterogeneity and the small
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430 sample size, robotic gait training is effective in individuals with cerebral palsy. The
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431 main findings show improvements in gait speed, gait endurance, and gross motor

432 function. Furthermore, the data suggest that this improvement is best observed in

433 people with cerebral palsy classified at levels I and II of GMFCS.

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435

436
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437 Study limitations

438 This systematic review is limited by the low level of evidence observed and the wide

439 range of GMFCS levels. Furthermore, none of the reviewed articles reported a priori

440 sample size calculation

441

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442 Conclusion

443 Regarding the study limitations, we cannot establish a cause-effect relationship

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444 between robotic gait training and improvements in gait function. However, the results

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445 obtained by the meta-analysis suggest that the training benefits people with cerebral

446 palsy, specifically by increasing walking speed and endurance and improving gross

447
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motor function. These benefits were observed in studies with a weekly frequency of
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448 training greater than or equal to four days per week and with a duration of training

449 greater than or equal to 30 minutes.

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450
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451 Despite the variability in the frequency and duration of training regimens, it is possible
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452 to identify significant positive results in studies that have proposed more intense

453 training.
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455 Regarding device configuration, it was not possible to identify the criteria for
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456 adjustment, thus making it difficult to establish evidence-based standards for

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457 scientifically adequate training using robotic devices.

458

459 For future studies, we suggest investigating device configuration parameters and

460 conducting a large number of randomized controlled trials with larger sample sizes

461 and individuals with homogeneous impairment.

462
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463 Disclosure of interests

464 The authors have stated that they had no interests which might be perceived as

465 posing a conflict or bias.

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764 changes in walking after stroke. Journal of neurologic physical therapy: JNPT.
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776 for undertaking reviews in health care. Centre for Reviews and Dissemination;
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780 meta-analysis in context. John Wiley & Sons; 2008.

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794 List of Figures
795
796 Figure1: PRISMA flow diagram.

797 Figure 2: Forest Plot of 6 minutes Walk Test.

798 Figure 3: Forest Plot of 10 meters Walk Test.

799 Figure 4: Forest Plot of GMFM D.

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800 Figure 5: Forest Plot of GMFM E.

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821 List of Tables

822 Table 1: Methodological quality of articles: Critical Review Form for Quantitative

823 Studies.

824 Table 2: Results of methodological quality of articles: Critical Review Form

825 Quantitative Studies

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826 Table 3: Summary of study characteristics: Single Subject Research Designs

827 Table 4: Summary of study characteristics: Group Research Designs

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Table 1

Critical Review Components

Study purpose

1- Was the purpose clearly stated?

Literature

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2- Was relevant background literature reviewed?

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Design

3-Was the design appropriate for the study question?

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Sample

4- Was the sample described in detail?

5- Was sample size justified?

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6- Were the outcome measures reliable?

7- Were the outcome measures valid?

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8- Was intervention described in detail?

9- Was contamination avoided?

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10-Was co-intervention avoided?

Results
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11-Were results reported in terms of statistical significance?

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12-Were the analysis methods appropriate?

13-Was clinical importance reported?

14-Were drop-outs reported?

Conclusions and clinical implications

15-Were conclusions appropriate given study methods and

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results?

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Table 2
Studies Questions

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Total

Borggrfe et al.27 1 1 1 0 0 1 1 0 1 1 1 1 1 1 1 12
28
Meyer-Heim et al. 1 1 1 1 0 1 1 0 1 1 1 1 1 1 1 13

Borggrfe et al.29 1 1 1 1 0 1 1 1 1 1 1 1 1 1 1 14
30
Borggrfe et al.(b) 1 1 1 1 0 1 1 1 1 1 1 1 1 1 1 14

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Arellano-Martnez et al.31 1 1 1 1 0 1 1 1 1 1 1 1 1 1 1 14

Verazaluce-Rodrguez et al.32 1 1 1 1 0 1 1 0 1 1 1 1 NA 1 1 12

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33
Schroeder et al. 1 1 1 0 0 1 1 0 1 1 1 1 1 1 1 12

Smania et al.29 1 1 1 1 0 1 1 0 1 1 1 1 1 1 1 13

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35
Romei et al. 1 1 1 0 0 1 1 0 1 1 1 1 1 1 1 12

Drubicki et al.36 1 1 1 1 0 1 1 0 1 1 1 1 1 1 1 13

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Number of Results Effect Size

Research Level of Participant Age Parameters for Outcome ICF
Study participants Equipment Intervention (Cohens d
design evidence characteristics (Range) intervention measures Dimension
Borggrfe Before After IV 24 Bilateral 4 - 21 Lokomat 12 sessions, 3 weeks, No reports 1. GMFM Function 1. GMFM 66 1. GMFM 66

et al., design spastic 4 sessions per week Dimension D and Dimension D Dimension D

200728 Ataxic 20 to 43 minutes per Dimension E Activity p = 0.003 d = 0.1986115

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GMFCS I-IV session.

2. 10mWT Dimension E. Dimension E

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p = 0.004 d = 0.1740771

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3. 6minWT

2. 10mWT 2. 10mWT

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p = 0.005 d = 0.2714188

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3. 6minWT 3. 6minWT

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p = 0.005 d = 0.2392387

D
Meyer- Before After IV 22 Bilateral 4 - 12 Lokomat 20 sessions, 3 to 5 No reports. 1. GMFM-66 Activity 1. GMFM-66 1. GMFM 66

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Heim et al., Design spastic sessions per week, 45 Dimension D. Dimension D. Dimension D

200929 GMFCS II - minutes per session. Dimension E. p < 0.05 d = 0.2098031

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IV

2. 10MWT Dimension E. Dimension E.

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p = 0.169 d = 0.0705761
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3. 6minWT

2. 10MWT 2. 10mWT

4. FAC p < 0.01 d = 0.2078338

3. 6minWT 3. 6minWT
p = 0.093 d = 0.154707
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4. FAC 4. FAC

p = 0.063 d = 0.242

Borggraefe Before - After IV 20 Bilateral 4,5 20,7 Lokomat 12 sessions, 4 sessions 1. BWS was 1. GMFM - 66 Activity 1. GMFM 66 1. GMFM 66

et al., Design Spastic per week, 50 minutes started at 100% Dimension D Dimension D Dimension D

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201030 GMFCS I-II per session and then reduced Dimension E p = 0.001 d = 0.1973145

(10) as much as

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GMFCS III- possible. Dimension E Dimension E.

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IV (10) p < 0.001 d = 0.1884934
2. The guidance

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individually

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adapted according

to clinical

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judgment.

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3. Walking speed

was initially set at

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km/h.

Borggraefe Before IV 14 Bilateral 4,5 19,2 Lokomat 12 sessions 1. Walking speed 1. GMFM - 66 Function 1. GMFM 66 1. GMFM 66

et al., 2010 After Design Spastic 3 weeks initially set at 1.1 Dimension D and Dimension D Dimension D

(b)31 GMFCS I-IV 4 sessions per week km/h increased to Dimension E Activity p = 0.003 d = 0.1457511

Mean 34 (+ 4) 1.8 km/h.

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minutes per session 2. 10mWT Dimension E. Dimension E

2. BWS reduce p = 0.004 d = 0.0838051

until the knee 3. 6minWT

collapse in 2. 10mWT 2. 10mWT

flexion during p = 0.005 d = 0.3518987

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stance.

3. 6minWT 3. 6minWT

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3. Force guidance p = 0.005 d = 0.3303943

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was set at 5%

higher than stop

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Arellano- Case Control IV 14 Hemiplegic 4 14 Lokomat 10 sessions 1. DGO group 1. GMFCS Activity GMFCS from II No raw data

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Martnez et GMFCS II 30 minutes Based on weight to I provided for

al., 201332 and 2. Gait Analysis: p = 0.042 calculation.

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anthropometrics Step length

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meausure Stride length Gait speed

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Lesft stride

p = 0.025
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Veraluce- Before After IV 33 Tetraplegic Mean age Lokomat 40 sessions, Blocks of 1. Gait velocity 1. GMFCS Activity 1. GMFCS No raw data

Rodriguez Design and 7,2 years 10 sesions, 2 sessions was initially set at 8 pacients provided for

et al., Double per week, 20 minutes 0.7-0.8 km/h and 2. Body Weight requalified as II calculation.

201433 Hemiplegia per session. the leading force Support (BWS) (24%).

GMFCS II at 100%.

and III 3. Speed 2.BWS

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p = 0.442

4. Guiding force

3. Speed

p = 0.081

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4. Guiding force

p = 0.662

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Schroeder Prospective IV 18 Bilateral 5 21,8 Lokomat 12 sessions, 3 weeks 1. BWS was 1. GMFM-66 Activity 1.GMFM 66 1. GMFM 66

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et al., Cohort Spastic training, 30 to 60 started at 100% Dimension D p < 0.001 Dimension D

201434 GMFCS I to minutes per session. and then reduced Dimension E d = 0.1270163

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possible. 2. 10mWT p < 0.01

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Dimension E

d = 0.1012577

2. The guidance 3. 6minWT Dimension E:

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force was p < 0.01 2. 10mWT

D
individually 4. COPM d=0

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adapted according 2. 10mWT

to clinical p > 0.05 3. 6minWT

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judgment d = 0.111111

3. 6minWT:
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p = 0.076
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4. COPM

Performance

p = 0.010

Satisfaction
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p = 0.046

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Table 4

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Number of Effect Size

Level of Participants Results (Cohens d)
Participant Age Parameters for Outcome ICF
Study Research design Evidence Equipment Intervention
characteristics (Range) intervention measures Dimension
(OCEBM) Treatment Control
Group Group
Diplegic or 10 - 18 Gait 10 sessions, 5 sessions 1. Step length and 1. 10mWT Activity and 1. 10mWT 1. 10mWT:

Smania et Randomized IIb 9 9 Tetraplegic Trainer I per weeks, 40 minutes gait speed were Function p = 0.008 d = 0.558

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al., 201135 Controlled Trial. GMFCS II -IV (GTI) per session. individually set 2. 6minWT

according to the gait 2. 6minWT 2. 6minWT:

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Experimental Group parameters recorded 3. Gait p = 0.008 d = 0.438

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30 min + 10 passive at the Analysis:

joint movement pre-treatment gait Sagittal plane 3. Gait Analysis

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analysis. The experimental

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Control Group Spatiotemporal group showed

40 min. Conventional 2. Walking speed gait parameters significant

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increased over the cadence, and speed and step

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course of the 2 step length). length

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weeks.

EP 3. The PBWS was

progressively
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to 0% over the

duration of the

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Romei et Cohort design III 9 10 Bilateral 4-16 Lokomat 40 sessions, 10 weeks, 1.body-weight 1. GMFM-66 Activity 1. GMFM-66: 1. . GMFM-88.

al., 201236 Spastic CP for 30 minutes per support fixed at 50% p > 0.05 Dimension D

GMFCS I - III session for the 2. GMFM-88 d = 0.356

entire duration of the Dimension D 2. GMFM-88.

RAGT+TOP group training and the Dimension E Dimension D Dimension E

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20 sessions of RAGT leading force at Dimension E d = 0.170

(2 sessions / week) + 100% 3. 6minWT p > 0.05

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20 of task-oriented 2. 6minWT

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physiotherapy 2. Gait velocity was 4. Gait 3. 6minWT: d = 0.084

(2 sessions / week). initially set at 1.2 Analysis p > 0.05

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km/h for all the (3DGA).

ITOP group children and was Walking speed, 4. 3DGA data:

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40 sessions gradually increased step length, p > 0.05

exclusively of task- to 1.6 stride length

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oriented physiotherapy km/h for the and cadence. 5. Gillette Gait

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(4 sessions/week). youngest children Index:

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(10% every 5 5. Gillette Gait p > 0.05

sessions) and Index

EP to 2.0 km/h for the

oldest children (20%

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Druzbicki Randomized IIb 26 9 Spastic 6 - 13 Lokomat 20 sessions, 4 sessions 1. Based on the 1.Gait Activity 1.Gait Analysis. No raw data

et al., Controlled Trial. Diplegia per weeks, 45 minutes measurement Analysis. Temporospatial provided for

201337 GMFCS II - per session. of the length of Temporospatial parameters: calculation.

III limbs, the range of parameters: p > 0.05

motion in the joints Stance phase

of the lower length 2. Gait Kinematic

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limbs, muscle tone, Double support parameters:

and body weight. length p > 0.05

Mean step

width

Mean gait

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speed

Mean step

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length

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Gait Kinematic

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parameters:

Range of pelvic

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motion.

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Highlights

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Highlights

Robotic gait training improves walking speed and endurance.

Robotic gait training improves gross motor function.

Consistent standards for the robotic device settings could not be

established.

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