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Intensive Mobility Training in Cerebral Palsy

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Intensive Mobility Training in Cerebral Palsy

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leidiana Eugenia da Paz

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Received: 9 January 2024 | Accepted: 19 June 2024

DOI: 10.1111/dmcn.16040

SYSTE M ATIC R EV I EW

Efficacy and threshold dose of intensive training targeting

mobility for children with cerebral palsy: A systematic review
and meta-analysis

Isabella Pessóta Sudati1,2 | Leanne Sakzewski2 | Carolina Fioroni Ribeiro da Silva1 |

1
Physical Therapy Department, Federal
University of São Carlos, São Carlos, São Abstract
Paulo, Brazil Aim: To systematically review the evidence for intensive mobility training in cerebral
2
Queensland Cerebral Palsy and palsy (CP) and to determine the minimum effective dose to improve mobility.
Rehabilitation Research Centre, Faculty of
Medicine, Child Health Research Centre, The Method: Randomized controlled trials (RCTs) or quasi-RCTs that included par-
University of Queensland, Brisbane, Australia ticipants with CP, and which used intensive task-oriented training (TOT) mobil-
3
Cerebral Palsy Alliance Research Institute, ity interventions and reported mobility outcomes, were included. Five databases
University of Sydney, Sydney, Australia were searched; two independent reviewers selected studies and extracted data. The
4
Physiotherapy Department, Perth Children's Grading of Recommendations Assessment, Development, and Evaluation system and
Hospital, Perth, Western Australia, Australia
5
the Cochrane Risk of Bias 2 tool were used to rate the certainty of evidence at the
The Healthy Strides Foundation, Perth,
Western Australia, Australia outcomes level and to determine the risk of bias respectively. Meta-analyses were con-
ducted with clinically homogeneous studies. Threshold dose was analysed through
Correspondence meta-regression.
Isabella Pessóta Sudati, Physical Therapy
Department, Federal University of São Carlos, Results: Forty-six RCTs with 1449 participants (mean age range 1 year 2 months to
Rodovia Washington Luís, km 235 -SP-310, 16 years 4 months) were included. TOT had statistically and clinically significant ef-
São Carlos, São Paulo, Brazil. fects on walking speed (p = 0.001), cadence (p = 0.02), gross motor function (p = 0.03),
Email: [email protected];
[email protected] and functional mobility (p = 0.009) compared with control interventions. The thresh-
old dose was undeterminable owing to the high heterogeneity of studies.
Funding information Interpretation: TOT may improve walking speed, walking endurance, and balance.
National Health and Medical Research
Council, Grant/Award Number: 1037220;
Studies with homogeneous samples and outcomes are needed to support clinical rec-
Cerebral Palsy Alliance Research Foundation, ommendations for intensive mobility interventions.
Grant/Award Number: PHD02221

[Correction added on 29 August 2024 after first online publication: The fourth affiliation was removed and the rest were reordered.]
Abbreviations: GMFM, Gross Motor Function Measure; RCT, randomized controlled trial; TOT, task-oriented training.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the
original work is properly cited.
© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

Dev Med Child Neurol. 2024;00:1–16. wileyonlinelibrary.com/journal/dmcn | 1

Cerebral palsy (CP) is a group of disorders of posture and

movement attributed to a permanent and non-progressive
disturbance to the developing brain, causing activity and What this paper adds
mobility limitations.1 Mobility is defined as the displace-
ment of the individual across a variety of environments, such • Intensive task-oriented training (TOT) improves
as home, school, and/or community, supporting the perfor- general mobility in children with cerebral palsy.
mance of daily activities.2 Considering the International • TOT may promote clinically important changes
Classification of Functioning, Disability and Health catego- on walking endurance and balance.
ries, mobility includes activities such as maintaining and/or • Treadmill training is effective to improve walking
changing body position, walking and moving, and carrying speed.
and moving objects.3 • Mobility protocols showed highly heterogeneous
parameters.
Treatment goals reported by children and adolescents • Studies with consistent reporting of outcome data
with CP and their families often target mobility.4 Although and intervention parameters are necessary.
a variety of treatments have been proposed to address these
goals,5 there are currently conflicting levels of evidence for
the available interventions and few studies that summarize
their efficacy with a high level of evidence to support reha- This study aimed to systematically review the available
bilitation clinicians.6 evidence for intensive TOT approaches to improve mobility
In the past few years, interventions using task-oriented, of children and adolescents with CP and to determine the
goal-directed activities have been suggested to provide minimum effective dose of treatment to achieve functional
greater benefit than general interventions.7,8 Task-oriented gains.
training (TOT) follows motor learning principles and in-
cludes activity training based on the goals set by the child
and/or family, and is delivered with specific parameters of M ET HOD
intensity, repetition, dose, and feedback, preferably in con-
text.9 TOT has been shown to be effective in improving gross Design and ethical approval
motor function,10 balance,11 and general mobility12 in chil-
dren with CP, with the promise of improving motor develop- This systematic review and meta-analysis followed the guide-
ment of infants up to 2 years of age diagnosed with, or at risk lines of the Cochrane Handbook for Systematic Reviews of
of, CP.13 Previous clinical practice guidelines have also sup- Interventions.20 A MeaSurement Tool to Assess systematic
ported general TOT, including walking or treadmill train- Reviews 2 (AMSTAR-2) recommendations21 were followed
ing, to improve walking speed and distance for children and and data were reported using the Preferred Reporting Items
young people with CP classified in Gross Motor Function for Systematic Reviews and Meta-Analyses (PRISMA) state-
Classification System (GMFCS) levels I to III.6 Similarly, ment.22 The review was registered in international prospec-
overground walking practice has been recommended to im- tive register of systematic reviews (PROSPERO), number
prove assisted walking distance for those with CP classified CRD42022371274.
in GMFCS level IV.6 Despite the available evidence, there is
still a gap in the literature about the effectiveness of TOT,
including different approaches to mobility training, and Search strategy
knowledge of the recommended dose to improve mobility
outcomes of children with CP. A comprehensive, systematic search was completed by inves-
Intervention dose includes the frequency, intensity, dura- tigator IPS in the following databases: PubMed/MEDLINE
tion, and type of intervention.14,15 The total amount of inter- (through the National Library of Medicine); Embase
vention hours has been reported as an important predictor (Elsevier); Central/Cochrane Library; SciELO Citation
of functional gains.14,16,17 Additionally, intensive training, Index (Web of Science); CINAHL (EBSCO). These databases
involving at least two sessions per week for a period of time,18 were searched from their inception to October 2023. Search
is recommended as being preferable to regular distributed updates were done every month as well as manual searches
therapy. A recent systematic review found that an average of from studies' references.
30 to 40 hours was a sufficient dose to improve general upper The search strategy comprised the following population,
limb function, and an average of 14 to 25 hours of practice intervention, comparison outcome (PICO) question: For in-
was sufficient to achieve individual goals of children with fants, children with CP and age up to 18 years (P), what is
CP.19 The minimum effective dose of mobility interventions the effectiveness and minimum effective threshold dose of
to achieve clinically meaningful changes in mobility out- intensive task-oriented mobility training (I) compared with
comes is currently unclear. Establishing the minimum dose other types of intervention or low-dose TOT (C) to improve
of treatment for functional mobility gains in children with mobility (O)?
CP is important to support the decision-making process and For this review, ‘mobility training’ included all active
to optimize health service delivery.14,18 activities (e.g. walking, running, going up and down steps,
EFFICACY AND THRESHOLD DOSE OF INTENSIVE TRAINING TARGETING MOBILITY FOR

and posture transfer activities) and self-initiated mobility independent reviewers (IPS, CFRS). Disagreements were re-
activities (e.g. self-initiated stepping, even if followed by as- solved by consensus and, when necessary, a third reviewer's
sistance), except assisted mobility (e.g. powered mobility). opinion (ACC) was requested.
‘Functional training’ encompassed all task-oriented inter- Study design, sample characteristics, and intervention
ventions focused on promoting functional skills, including parameters were tabulated. If needed, study authors were
everyday activities and exercises.6,23–25 Search terms are contacted to obtain additional information. In case of no re-
available in Appendix S1. sponse, the article was excluded. More details are outlined
in Appendix S3.
At the outcomes level, the certainty of evidence of seven
Selection criteria main outcomes was made using Grading of Recommendations
Assessment, Development and Evaluation (GRADE)28 by
Inclusion criteria for the systematic review were as follows: (1) two independent reviewers (IPS, MH) and disagreements
randomized controlled trial (RCT) or quasi-RCT; (2) at least were resolved by consensus.
50% of participants had CP; (3) the mean age of the cohort
was up to 18 years; (4) studies reported mobility outcomes
(tools included are listed in Appendix S2); (5) interventions Data analysis
included active mobility (e.g. overground walking training;
treadmill training with or without partial-weight suspen- Meta-analyses were conducted for the clinically homogene-
sion; cycling training; functional strengthening; dual-task ous studies. The analyses were based on the postintervention
training; plyometric training); (6) intervention frequency mean and standard deviation outcome scores, which could be
of at least two sessions per week;18,26 and (7) at least 50% of extracted or calculated from the studies. Only results of the
experimental intervention was TOT. There were no restric- time point immediately after the intervention were included.
tions for language or publication period. Additionally, studies were divided into subgroups according
Studies were excluded if they were (1) review studies to outcome measures reported (e.g. Gross Motor Function
of any type, protocol or feasibility studies; (2) non-peer- Measure [GMFM] dimensions D and E) and CP subgroups
reviewed publications (e.g. conference abstract or paper, (GMFCS levels, motor types, and motor distributions).
thesis, dissertation, commentary, letter to editor); (3) de- Review Manager software (RevMan 5.4), developed by
signed as non-randomized or crossover studies; (4) not Cochrane Collaboration in London, UK, was used for quan-
focused on mobility outcomes; (5) studies that included titative data analysis to determine effect sizes from each
only a neurodevelopmental approach and/or those where study. Effect sizes for continuous outcomes were considered
active mobility activities were a minor part of the session; small (0.2), moderate (0.5), large (0.8), and very large (1.3).29
(6) focused on pharmacological (e.g. botulinum neurotoxin, Mean differences and standardized mean differences with
lidocaine), invasive (e.g. needling, acupuncture), or post- 95% confidence intervals (CI) were calculated for treatment
surgical approaches (e.g. tenotomy, rhizotomy); (7) studies and control group comparisons. Pooled treatment effects
where mobility was not the main aspect of interest when were calculated across trials by using a fixed-effects model
comparing groups (e.g. treadmill training vs treadmill when trials used similar interventions and outcomes on
training plus functional electrical stimulation; transcuta- similar populations. Statistical heterogeneity was assessed
neous electrical nerve stimulation or transcranial direct by the I2 statistic and considered as not important (0–40%),
current stimulation; overground walking vs overground moderate (30–60%), substantial (50–90%), or considerable
walking plus orthosis; pedometer-based gait training); or (75–100%).20 When substantial or considerable heterogene-
(8) intervention not based on self-initiated mobility (e.g. ity (I2 > 50%) between studies was evident, a random-effects
suit therapy; aquatic therapy; passive stretching; virtual re- model was used. Forest plots were used to graphically illus-
ality interventions where the participant remained seated; trate the results of meta-analysis. The effectiveness of each
hippotherapy; vibration therapy). intervention was assessed by between-groups effect sizes and
Two reviewers (IPS, ACC) independently selected studies statistical significance. Sensitivity analyses explored the ro-
on the basis of title and abstract. Abstracts meeting inclu- bustness of the results by excluding high risk of bias studies
sion criteria or those that required more information to de- from the meta-analysis.
termine inclusion were retained for full-text review. Articles A meta- regression was conducted to investigate the
were included when 100% agreement between reviewers was threshold dose using Stata SE version 18.0 (StatCorp, College
achieved. Covidence software was used in all stages. Station, TX, USA). GMFM, 6-Minute Walk Test, Timed Up
and Go Test, Pediatric Balance Scale, and walking speed
were the outcomes included for this analysis. A random-
Quality assessment, data extraction, and effects linear mixed method was used, with treatment dose
evidence-based recommendations as the moderator and using mean difference or standard
mean difference (Cohen's d) according to the available data
The methodological quality of included studies was assessed for each outcome. A p-value of less than 0.05 was considered
using the Cochrane Risk of Bias 2 tool (RoB 2),27 by two significant.
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4 | SUDATI et al.

TA BL E 1 Study design and sample characteristics.

Experimental intervention Control intervention

Sample size Sample size

References Study design (n) Mean age (SD) / GMFCS / CP type (n) Mean age (SD) / GMFCS / CP type
39
Ameer et al. RCT 10 6.2 (1.07) / I; II / BCP 10 6.2 (1.35) / I; II / BCP
40
Aras et al. RCT 10 NM / II; III / Mixed 10 NM/ II; III / Mixed
Arnoni et al.48 RCT 11 8.56 (2.4) / I / UCP 11 8.24 (2.1) / I / UCP
Badaru et al.73 RCT 23 8.7 (3) / I–III / Mixed 23 7.9 (3.1) / I; III / Mixed
74
Bar-haim et al. RCT 38 8.93 (1.7) / II; III / BCP 38 8.79 (1.7) / II; III / BCP
Mattern-Baxter et al.41 Quasi-RCT 9 1.72 (0.51) / I; II / BCP 10 1.70 (0.44) / I; II / BCP
Bjornson et al.36 RCT 6 7.7 (2.3) / II; III / BCP 6 9.4 (2) / II; III / BCP
Bleyenheuft et al.75 Quasi-RCT 10 10.5 (2.8) / II–IV / BCP 10 11.4 (3.9) / II–IV / BCP
42
Bryant et al. SB-RCT 12 13.5 (2.6) / IV; V / BCP 12 C1: 13.8 (2.3)
C2: 14.3 (1.9)a/ IV; V / BCP
Chaovalit et al.30 SB-RCT 19 7.1 (2.1)b / III; IV / Mixed 19 8.7 (2.6)b / III; IV / Mixed
56
Chen et al. RCT 13 8.7 (2.1) / I–II / Mixed 15 8.5 (2.2) / I; II / Mixed
58
Chen et al. RCT 13 8.7 (2.1) / I–II / Mixed 14 8.6 (2.2) / I; II / Mixed
Cho and Lee72 RCT 13 5.54 (1.81) / I–III / BCP 12 7.17 (2.17) / I–III / BCP
Chrysagis et al.44 SB-RCT 11 15.9 (1.97) / I–III / BCP 11 16.09 (1.51) / I–III / BCP
31
Crompton et al. SB-RCT 8 11.2 (1.9) / I–II / BCP 7 9.9 (2.5) / I–III / BCP
Damiano et al.57 RCT 12 9.2 (2.9) / I–III / BCP 13 11.4 (4) / I–III / BCP
37 b
Fowler et al. SB-RCT 29 11.1 (3.3) / I–III / BCP 29 11.6 (2.7)b / I–III / BCP
60 b
Franki et al. SB-RCT 23 5.7 (1.4) / I–III / BCP 23 6.4 (1.3)b / I–III / BCP
Gibson et al.32 SB-RCT 21 12.4 (2.7) / I–III / Mixed 21 12.5 (2.8) / I; II / Mixed
Goswami et al.76 RCT 30 6.1 (2.7)b / II–III / BCP 29 5.9 (1.8)b / II; III / BCP
Grecco et al.38 SB-RCT 7 6.8 (2.6) / I–III / NM 7 6 (1.5) / I; III / NM
Grecco et al.43 SB-RCT 17 6.8 (2.6) / I–III / NM 17 6 (1.5) / I; III / NM
77
Gurusamy et al. DB-RCT 20 8.2 (2.3) / I–III / BCP 20 8.75 (2.78) / I; III / BCP
Hilderley et al.78 SB-RCT 10 11.75 (2.58) / I–II / Mixed 8 12.17 (2.75) / I; II / Mixed
Hurd et al.59 SB-RCT 12 1.18 (0.42)b / I–II / UCP 13 C1: 1.93 (0.81)b
C2: 1.76 (0.57)a,b / I; II / UCP
Johnston et al.33 RCT 14 9.6 (2.1)b / II–IV / BCP 12 9.5 (2.3)b / III; IV / BCP
49
Jung et al. SB-RCT 5 12.8 (1.6) / I–II / BCP 5 12 (2.53) / I; II / BCP
Kimoto et al.61 SB-RCT 10 10.8 (4.3)b / I–II / BCP 11 10.9 (4.1) / I; II / BCP
62
Ko et al. SB-RCT 9 4.9 (1.1) / I–III / Mixed 9 5.1 (1.5) / I–III / Mixed
Kusumoto et al.63 SB-RCT 8 16.3 (2.1) / I–III / BCP 8 15 (2) / I–III / BCP
65
Lee et al. RCT 13 6.3 (2.1) / II–III / Mixed 13 6.3 (2.9) / II; III / Mixed
Lee et al.64 SB-RCT 9 6.1 (2.7) / I–III / Mixed 8 6.9 (2.5) / I–III / Mixed
34
Liao et al. SB-RCT 10 7.13 (1.7) / I–II / BCP 10 7.6 (1.46) / I; II / BCP
Mitchell et al.35 RCT 51 11.3 (2.3) / I–II / UCP 50 11.3 (2.5) / I; II / UCP
66
Ogwumike et al. RCT 23 8.7 (3) / I–III / Mixed 23 7.9 (3.1) / I–III / Mixed
Peungsuwan et al.67 RCT 8 13.5 (3.3) / I–III / Mixed 7 13 (4.16) / I–III / Mixed
Ren et al.50 RCT 19 4.5 (1.16)b / I–II / BCP 16 4.75 (0.8) / I; II / BCP
Sajan et al.51 SB-RCT 10 10.6 (3.78) / II–IV / BCP 10 12.4 (4.93) / I–IV / BCP
Salem et al.68 SB-RCT 5 6.3 (1.72) / I–III / BCP 5 6.76 (2.05) / I–III / BCP
53
Saussez et al. RCT 20 9.0 (3.1) / I–II / UCP 20 9.1 (2.9) / I; II / UCP
Scholtes et al.69 SB-RCT 24 10.3 (1.9) / I–III / Mixed 24 10.2 (2.2) / I–III / Mixed
70
Schranz et al. RCT 15 13.4 (2.4) / I; II / Mixed 12 12.2 (2.7) / I; II / Mixed
EFFICACY AND THRESHOLD DOSE OF INTENSIVE TRAINING TARGETING MOBILITY FOR

TA BL E 1 (Continued)

Experimental intervention Control intervention

Sample size Sample size

References Study design (n) Mean age (SD) / GMFCS / CP type (n) Mean age (SD) / GMFCS / CP type
71
Surana et al. RCT 12 5.8 (2.3) / I; II / UCP 12 5.1 (2.6) / I; II / UCP
Swe et al.45 SB-RCT 15 13.03 (3.56) / II; III / Mixed 15 13.37 (3.32) / II; III / Mixed
Uysal and Baltaci52 SB-RCT 12 9.13 (2.57) / I; II / UCP 12 10.11 (2.62) / I; II / UCP
Willoughby et al.46 SB-RCT 12 10.35 (3.14) / III; IV / NM 14 11.24 (4.17) / III; IV / NM

Ages are presented in decimal years as presented in original studies.

See Table S1 for more details.
Abbreviations: BCP, bilateral cerebral palsy; C1, control intervention 1; C2, control intervention 2; DB-RCT, double-blind randomized controlled trial; F, female; GMFCS,
Gross Motor Function Classification System; M, male; NM, not mentioned; quasi-RCT, quasi-randomized controlled trial; RCT, randomized controlled trial; SB-RCT, single-
blind randomized controlled trial; SD, standard deviation; UCP, unilateral cerebral palsy.
a
Second control intervention.
b
Calculated by the authors.

R E SU LT S Treadmill training

Summary of studies A total of 11 studies investigated the effectiveness of tread-

mill training.33,37,38–46 Partial bodyweight-supported tread-
A total of 3079 studies were identified by the comprehensive mill training was compared against overground training,
search, 2532 being screened by titles and abstracts. Of these, functional training, or assisted mobility (n = 4);33,40,45,46
46 RCTs, ranging from publication years 2007 to 2023, met treadmill training alone versus overground training, con-
the inclusion criteria (Figure S1). A summary of included trol intervention, or cycling training (n = 4);38,42–44 tread-
studies' characteristics is presented in Table 1 and a com- mill training plus control intervention in comparison with
plete version is shown in Table S1. The 46 studies included control intervention alone (n = 1);39 and comparisons across
a total of 1449 participants. Mean ages ranged from 1 year different treadmill training frequencies (n = 2).36,41 The total
2 months to 16 years 4 months and GMFCS levels from I dose varied between 7 hours and 27 hours, and the study
to V, with a higher predominance of levels I to III (n = 40 lasted from 2 weeks to 12 weeks. The frequency and duration
studies). of sessions ranged from two to 10 sessions per week, and 20
Risk of bias was high for 29 studies (Figure 1). The most to 45 minutes per session, respectively (Table 2 and Table S2).
common reasons for high risk were biases due to deviations The treadmill training was effective when compared with
from intended intervention and outcome measurement control intervention for walking speed (standardized mean
(Appendix S4). difference 0.83 [95% CI 0.33–1.34], p = 0.001) (Figure 2a).
All included studies had a high level of intervention Gross motor function and walking endurance were also in-
acceptability among the participants. The overall drop- cluded for meta-analysis; however, no significant differences
out rates ranged from 0% to 40%, with most occurring were found (Figure 2b,c respectively). The mean effect on
before the intervention started, and not because of ad- walking endurance, however, exceeded the 23-metre min-
verse effects. Only 17% of studies reported adverse imal clinically important change for the 6-Minute Walk
health effects, with pain and fatigue being the most fre- Test.47 The effect of treadmill training on walking speed,
quently mentioned. 30–37 Feasibility results are reported in walking endurance, and gross motor function outcomes was
Appendix S5. rated as low certainty evidence (Table 3).

Summary of effectiveness findings Virtual reality

A total of 23 studies were eligible for meta- analyses. Six studies investigated the effectiveness of virtual real-
Interventions were grouped into four categories: treadmill ity plus control intervention versus control intervention
training; virtual reality training; cycling training; and func- alone.48–53 The total dose of virtual reality training varied
tional training. A general description of the interventions' between 12 and 40 hours, ranging from a frequency of two
content and parameters is presented in Table 2, with more to six sessions per week, duration of 20 to 50 minutes per
details given in Table S2. Detailed mobility results are re- session, and a study duration of 2 to 12 weeks (Table 2 and
ported in Appendix S6. Table S2).
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6 | SUDATI et al.

Virtual reality was effective in improving cadence com-

pared with control intervention (mean difference 6.33 [95%
CI 1.10–11.56], p = 0.02) (Figure 3a). The mean difference
exceeded the five steps per minute minimal clinically im-
portant change for cadence.54 The effect of virtual reality
on cadence was rated as low certainty evidence (Table 3).
Improvements in dynamic balance measured by the Pediatric
Balance Scale favoured virtual reality over control; however,
it did not reach statistical significance (Figure 3b). The mean
difference, however, exceeded the 3.6 points minimal clini-
cally important change.55 Walking speed was also included
for meta-analysis; however, no significant effects were found
(Figure 3c).

Cycling training

Five studies investigated the effectiveness of cycling train-

ing delivered in community- based clinics or at home
against control intervention, treadmill training, elliptical
training, or no intervention.37,42,56–58 The total dose varied
from 9 to 30 hours, with a frequency of two to five sessions
per week, and 6 to 12 weeks' duration; each session varied
from 20 to 60 minutes (Table 2 and Table S2). Owing to the
large heterogeneity of outcomes, meta-analysis was not
possible.

Functional training

A total of 26 studies were included under this cate-

gory. 30,31,34,35,59–78 The studies within this category used
a diverse range of intervention elements, including re-
sistance training, endurance training, and circuit train-
ing, some of which were administered in a home setting.
The total dose of functional training varied between 6
hours and 84.5 hours, with a frequency of two to seven
sessions per week, a duration of 2 to 20 weeks, and each
session ranging from 15 to 390 minutes (Table 2 and
Table S2).
When aiming to improve gross motor function for children
with CP, functional training alone was effective when com-
pared with control intervention (standardized mean differ-
ence 0.30 [95% CI 0.03–0.58], p = 0.03) (Figure 4a). The effect
of functional training on gross motor function outcome was
rated as low certainty evidence (Table 3). One meta-analysis
assessing the effectiveness of functional training in improv-
ing general mobility, measured by the Timed Up and Go
Test, showed a significant overall effect favouring functional
training (mean difference − 3.37 [95% CI −5.90 to −0.83],
p = 0.009) (Figure 4b) and the mean effect exceeded the min-
imal clinically important change for Timed Up and Go Test,
which ranges from 0.22 to 5.31 seconds depending on GMFCS
level.79 The effect of functional training on Timed Up and Go
Test was rated as very low certainty evidence (Table 3).
FIGU R E 1 Risk of bias of included studies.
EFFICACY AND THRESHOLD DOSE OF INTENSIVE TRAINING TARGETING MOBILITY FOR

TA BL E 2 Experimental and control interventions.

Experimental intervention

Reference Content Intervention parameters

39
Ameer et al. TT + CT 8w; 3x/w; 20 min/session; 8 total hours +18 hours of CT
Aras et al.40 PBWSTT 4w; 5x/w; 45 min/session; 15 total hours
Arnoni et al.48 VR + CT 8w; 2x/w; 45 min/session; 12 total hours +13.3 hours of CT
73
Badaru et al. FT 12w; 2x/w; 40 min/session; 16 total hours
Bar-haim et al.74 FT 12w; 3x/w; 60 min/session; 36a total hours
41
Mattern-Baxter et al. HP; High-intensity TT 6w; 5x/w; 20 min/session; 10a total hours
36
Bjornson et al. TT 4w; 5x/w; 30 min/session; 10a total hours
Bleyenheuft et al.75 FT; HABIT-ILE 2w; 7x/w; 390 min/session; 84.5 total hours
Bryant et al.42 TT 6w; 3x/w; 30 min/session; 9a total hours
Chaovalit et al.30 FT + CT 6w; 5x/w; 30 min/session; 15 total hours +15 hours of CT
Chen et al.56 HP; Cycling 12w; 3x/w; 40 min/session; 24a total hours
Chen et al.58 HP; Cycling 12w; 3x/w; 40 min/session; 24a total hours
72
Cho and Lee FT 6w; 3x/w; 30 min/session;9a total hours
Chrysagis et al.44 TT 12w; 3x/w; 45 min/session; 27a total hours
31
Crompton et al. FT; LL 6w; 2x/w; 60 min/session; 12a total hours
Damiano et al.57 HP; Cycling 12w; 5x/w; 20 min/session; 20a total hours
37
Fowler et al. Cycling 12w; 3x/w; 60 min/session; 30a total hours
60
Franki et al. FT; Individually defined training 10w; 3.7 x/w; 43.3 min/session; 26.7a total hours
Gibson et al.32 HP; Running 12w; 2x/w; 60 min/session; 24a total hours + 24a hours of CT
76
Goswami et al. HP; FT; Parent-supervised NM; 15x/w; NM; NM
38
Grecco et al. TT 7w; 2x/w; 30 min/session; 7a total hours
43
Grecco et al. TT 7w; 2x/w; 30 min/session; 7a total hours
Gurusamy et al.77 FT 6w; 3x/w; 45–60 min/session; 18a total hours
78
Hilderley et al. FT; Speed, agility, and coordination LL 6w; 2–3w; 45 min/session; 12a total hours
Hurd et al.59 FT (immediate) 12w; 4x/w; 60 min/session; 48a total hours
33
Johnston et al. PBWSTT 2w; 10x/w; 30 min/session; 10a total hours
49
Jung et al. VR + CT 6w; 3x/w; 40 min/session; 12a total hours + 12a hours of CT
Kimoto et al.61 HP; FT; Loaded sit-to-stand training 8w; 3x/w; NM; NM
Ko et al.62 FT 8w; 2x/w; 60 min/session; 16a total hours
Kusumoto et al.63 HP; FT; Loaded sit-to-stand training 6w; 3–4x/w; 15 min/session; 6a total hours
65
Lee et al. FT 5w; 3x/w; 60 min/session; 15a total hours
Lee et al.64 FT + CT 6w; 3x/w; 30 min/session; 9a total hours; + 9a hours of CT
34
Liao et al. HP; FT + CT; Loaded sit-to-stand 6w; 3x/w; 20–30 min/session; 9a total hours + CT
programme
Mitchell et al.35 HP; FT 20w; 6x/w; 30 min/session; 32.4 total hours
66
Ogwumike et al. FT + CT 12w; 2x/w; 40 min/session; 16a total hours
67
Peungsuwan et al. FT + CT 8w; 3x/w; 70 min/session; 28a total hours
Ren et al.50 VR + CT 12w; 5x/w; 40 min/session; 40a total hours; + 40a hours of CT
51
Sajan et al. VR + CT 3w; 6x/w; 45 min/session;13.5a total hours; + 36 hours of CT
68
Salem et al. FT 5w; 2x/w; NM; NM
53
Saussez et al. VR during HABIT-ILE 1w; 5x/w; NM; 37 total hours + 53a hours of HABIT-ILE alone
69
Scholtes et al. FT 12w; 3x/w; 45–60 min/session; 36a total hours
Schranz et al.70 FT; High-intensity circuit training 8w; 3x/w; 28 min/session; 11.2a total hours
71
Surana et al. HP; FT; LL 9w; 5x/w; 120 min/session; 90 total hours
45
Swe et al. PBWSTT 8w; 2x/w; 30 min/session; 8a total hours

(Continues)
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8 | SUDATI et al.

TA BL E 2 (Continued)

Experimental intervention

Reference Content Intervention parameters

52
Uysal and Baltaci VR + CT 12w; 2x/w; 30 min/session; 12a total hours + 18a hours of CT
46
Willoughby et al. PBWSTT 9w; 2x/w; 30 min/session; 9a total hours
a
Calculated by the authors.
See Table S2 for more details.
Abbreviations: CT, conventional therapy; FT, functional training; HABIT, hand-a rm bimanual intensive therapy; HABIT-ILE, hand-a rm bimanual intensive therapy
including lower extremity; HP, home programme; LL, lower limb training; NM, not mentioned; PBWSTT, partial bodyweight-supported treadmill training; TT, treadmill
training; UL, upper limb training; VR, virtual reality; W, weeks; X, times.

F I G U R E 2 Comparison of effectiveness of treadmill training versus control interventions. (a) Treadmill training versus control intervention on
walking speed measured by self-selected velocity during gait. (b) Treadmill training versus control intervention on gross motor function measured by
Gross Motor Function Measure. (c) Treadmill training versus control intervention on walking endurance measured by 6-Minute Walk Test.

Two meta-analyses were conducted for mobility limita- Recommended threshold dose for mobility
tions, assessed by the Mobility Questionnaire (MobQues28) training
and walking speed, with no significant differences found
between functional training and control intervention With the available data, it was not possible to determine the
(Figure 4c,d respectively). The effect of functional training recommended threshold dose for mobility training. None of
on walking speed was rated as very low certainty evidence the outcomes showed a significant result for dose implemen-
(Table 3). A meta-analysis was conducted to assess the ef- tation and outcome change (Appendix S8).
fectiveness of general functional training on gross motor
function. It included studies delivering functional training
alone or functional training plus control intervention, both DISC US SION
compared with control intervention alone. No significant
differences were found (Figure 4e). This systematic review aimed to investigate the effectiveness
and minimum effective threshold dose of intensive TOT
compared with control interventions to improve mobility
Sensitivity analysis in children with CP. Owing to large heterogeneity, the TOT
interventions were grouped into four categories (treadmill,
We conducted sensitivity analyses by excluding studies virtual reality, cycling, and functional training). Compared
with high risk of bias from the meta-analyses whenever with control interventions, TOT overall showed statistically
possible. Only one meta-analysis, comparing the effect of significant and clinically meaningful changes in mobility
treadmill training versus control on walking speed, main- outcomes.
tained the significance of the results after sensitivity analysis Our meta-analysis favoured treadmill training as an ef-
(Appendix S7). fective intervention for improving walking speed, although
TA BL E 3 Certainty of evidence according to Grading of Recommendations, Assessment, Development and Evaluations.

Certainty assessment

Publication
Outcomes Number of studies Risk of bias Inconsistency Indirectness Imprecision bias Absolute effect (95% CI) Certainty
Category: treadmill training versus control
Walking speed (m/s) 3 Seriousa Not serious Not serious Seriousb None SMD 0.83 SD (0.33 to 1.34) ⨁⨁◯◯
Low
Gross motor function 2 Not serious Seriousc Not serious Seriousb None SMD 1.11 SD (−0.33 to 2.54) ⨁⨁◯◯
(GMFM total score) Low
Walking endurance 2 Not serious Seriousc Not serious Seriousb None MD 59.74 (−45.6 to 165.09) ⨁⨁◯◯
(6MWT) Low
Category: virtual reality training versus control
Cadence 2 Seriousa Not serious Not serious Seriousb None MD 6.33 SD (1.1 to 11.56) ⨁⨁◯◯
Low
CHILDREN WITH CEREBRAL PALSY: A SYSTEMATIC REVIEW AND META-A NALYSIS

Category: functional training versus control

EFFICACY AND THRESHOLD DOSE OF INTENSIVE TRAINING TARGETING MOBILITY FOR

Walking speed (m/s) 4 Very seriousd Not serious Not serious Seriousb None MD 0.36 (−0.06 to 0.77) ⨁◯◯◯
Very low
Gross motor function 5 Seriousa Not serious Not serious Seriousb None SMD 0.3 SD (0.03 to 0.58) ⨁⨁◯◯
(GMFM total score) Low
Mobility (Timed Up and 3 Very seriousd Not serious Not serious Seriousb None MD −3.37 (−5.9 to −0.83) ⨁◯◯◯
Go Test) Very low

Abbreviations: 6MWT, 6-M inute Walk Test; CI, confidence interval; GMFM, Gross Motor Function Measure; MD, mean difference; SD, standard deviation; SMD, standardized mean difference.
a
High risk of bias in at least one study (just one domain in each study).
b
Fewer than 200 participants per group.
c 2
I heterogeneity statistic is large.
d
High risk of bias in more than two domains in the same study (e.g. Badaru et al.73).
|
9

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10 | SUDATI et al.

F I G U R E 3 Comparison of effectiveness of virtual reality versus control interventions. (a) Virtual reality versus control intervention on cadence
measured by self-selected velocity during gait. (b) Virtual reality versus control intervention on balance measured by Pediatric Balance Scale. (c) Virtual
reality versus control intervention on walking speed measured by self-selected velocity during gait.

the certainty of evidence was low. We highlight that, even which are important modulators of neuroplasticity in chil-
after conducting sensitivity analysis, our results remained dren.9,86 Nevertheless, as virtual reality is delivered in indoor
statistically significant, in agreement with recommenda- environments and often within restricted areas, mobility
tions from Jackman et al.6 Treadmill training showed a practice may be limited. Virtual reality may therefore be
trend for improving walking endurance. The effect size, recommended as a complementary intervention to improve
however, exceeded the 23-metre threshold for clinically im- balance and walking cadence. Virtual reality interventions
portant change.47 Treadmill training may therefore be rec- could supplement TOT in real-life environments for appro-
ommended for improving walking speed and endurance for priate context-focused practice and carry over into daily
children with CP. Our findings are consistent with previous function and participation.87
systematic reviews.80–82 Treadmill training, however, was Even though meta-analysis was not possible for cycling
shown not to improve gross motor function. The GMFM training, significant improvements in endurance, gross
assesses multiple areas of gross motor ability, not just walk- motor function,37 and strength37,57 were found in the studies
ing.83 With current understandings of goal-directed and that included ambulatory children. Only one of the stud-
task-specific practice, outcome changes are expected in the ies42 included non-ambulatory children, demonstrating that
same area as the specific intervention that is being prac- the mean change in GMFM-88 dimension D was higher in
tised. Consequently, improvements in walking ability from those practising cycling training than in those in the tread-
a walking-specific intervention may not be reflected by a mill training and control groups. As cycling training can
broader assessment such as the GMFM. This intervention be a feasible opportunity for physical activity participation
presents several advantages including good implementation and functional task practice in non-ambulatory children,88
feasibility and contextual flexibility by means of portable studies with more homogeneous outcomes are needed so
treadmills which can be used in a clinic, home, or school set- stronger recommendations can be made. Only one current
ting. Treadmill training can be a valuable option to promote protocol study was found to explore cycling training in
a gradual transition to real-life environments, and to safely moderate-to-severe bilateral CP,89 highlighting the need for
increase the dose of walking practice.6,84 additional research in this area.
Virtual reality was shown to be effective in improving Functional training was the most prevalent and miscella-
walking cadence in CP when compared with control inter- neous intervention category in our review. Owing to the lack
ventions. It demonstrated a clinically meaningful change in of consensus definition,90 we considered ‘functional train-
cadence54 and balance,55 even though the result for balance ing’ as a diverse range of active interventions that did not re-
was not statistically significant. Previous studies have sup- quire specific technological equipment to be delivered.23 In
ported virtual reality to encourage autonomy and reduce this category, there were two subcategories of interventions:
pain and anxiety.81 A key benefit of virtual reality is the po- those exclusively focused on functional training and those
tential for motivation and enjoyment of the intervention,85 combining functional training and conventional training
EFFICACY AND THRESHOLD DOSE OF INTENSIVE TRAINING TARGETING MOBILITY FOR

F I G U R E 4 Comparison of effectiveness of functional training versus control interventions. (a) Functional training alone versus control intervention
on gross motor function measured by Gross Motor Function Measure. (b) Functional training versus control intervention on functional mobility
measured by Timed Up and Go Test. (c) Functional training versus control intervention on Mobility Questionnaire MobQues28 and MobQues47. (d)
Functional training versus control intervention on walking speed measured by self-selected velocity during gait. (e) General functional training versus
control intervention on gross motor function measured by Gross Motor Function Measure.

(e.g. routine physiotherapy, neurodevelopmental therapy). however, is required to improve the strength of this recom-
No previous systematic reviews in similar topics have cat- mendation. The effects of functional training are heteroge-
egorized different types of functional intervention, limiting neous,18,91–93 which may be caused by the large variability
the comparison with the current systematic review results. in definitions of functional therapy, intervention types, or
Functional training alone was effective in improving motor learning principles incorporated in the interventions.
gross motor function and general mobility, while protocols Additional challenges include notable heterogeneity in du-
combining functional training with conventional training ration, frequency, and intensity of the interventions, which
showed no statistically significant effect in reducing mobil- further limit grouping and accurate recommendations on
ity limitations and improving walking speed in the meta- threshold dose. Even though these intervention parame-
analyses, despite trends being observed. Functional training ters are believed to increase the efficacy of interventions,9,94
alone can therefore be recommended to improve gross motor strategies used to promote children's motivation and en-
function and general mobility outcomes compared with gagement, to progress the task challenge level task, and to
control interventions. Research with robust methodology, implement the planned intervention dose are infrequently
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12 | SUDATI et al.

reported. Future studies should therefore implement these We highlight that dose is one of the many important
parameter definitions and appropriately describe these in parameters to make an intervention effective. Studies are
methodology. encouraged to follow appropriate reporting guidelines for
Although TOT is based on motor learning theory in- intervention studies, facilitating the reproduction of the
corporating key principles such as the active involvement intervention by therapists and researchers, and favouring
of the individual while performing a specific context-based standardized reporting of outcomes for future systematic
task, studies usually provided limited descriptions of the reviews and meta-analyses.
strategies used to meet these principles.95,96 This lack of To our knowledge, this is the first systematic review
information limits the reproducibility of interventions.97 summarizing intensive interventions that aimed to improve
We highlight the importance of pilot or feasibility studies mobility in CP, where the children played an active role in
reporting implementation data and detailed intervention task-oriented activities. In addition, this is the first study
protocols to facilitate and encourage reproducibility by ther- that aimed to find the threshold dose for mobility interven-
apists in their clinical practice. In addition, studies reporting tions for children with CP, which so far is only available for
the type of motor learning strategies adopted (e.g. feedback, interventions targeting upper limb function.19 Assessing
task progression) and how they were implemented are also the effectiveness of mobility interventions may offer valu-
encouraged. able guidance to clinicians in selecting the best treatment
In addition to choosing the most effective intervention for each outcome while adhering to recommended dosage
according to the desired outcome, one must also consider parameters. This study followed the highest methodological
the intervention's potential adverse effects and acceptabil- recommendations for systematic review designs.
ity. Lower limb training involves activities that generate The contribution of the findings is limited by the inabil-
impactful joint movements and may require large ranges ity to provide stronger recommendations owing to the sub-
of motion, with the involvement of larger muscle groups. stantial heterogeneity in outcome measures, which limited
Participants receiving these interventions may therefore be a grouping of results. The high variability in reporting the
susceptible to pain, fatigue, and other adverse effects. In this results of the same outcome posed challenges in reaching
review, only eight studies reported adverse effects related to a comprehensive conclusion for each category of training
the training, such as pain and fatigue.30–37 In addition, feasi- (e.g. reporting the GMFM percentage rather than score,
bility components, such as positive and challenging aspects using metres per minute instead of metres per second in the
of intervention implementation, adverse effects, adherence, 10 Meter Walk Test), which usually affected ability to con-
and acceptability, were not frequently reported or explored. vert standard deviations, as well as reporting group mean/
Future intensive mobility intervention studies are encour- median and standard deviation/interquartile range data at
aged to explore and report these components to increase the pre-and postintervention and not just mean differences). In
reproducibility of interventions and better understand the addition, some meta-analyses showed a high heterogeneity
safety and acceptability of different interventions for vary- of participants' characteristics. Our study also encountered
ing populations. limitations stemming from small sample sizes within indi-
Among the feasibility parameters that should be consid- vidual studies and the scarcity of high-quality research. For
ered, the intervention dose is highlighted. In this review, we future research, we strongly recommend conducting inves-
faced significant challenges in defining the threshold dose tigations of the individual response to interventions, using
for intensive mobility training. The high heterogeneity and single-subject design followed by RCTs that adhere to rigor-
variability in reported outcomes results, coupled with in- ous methodological standards. Adopting validated and re-
consistencies and biases in study reporting, presented ob- liable assessment tools, along with substantial sample sizes,
stacles to establish a clear threshold dose. In addition, the would enhance the quality and robustness of subsequent
people with CP exhibit a notably higher variability in char- studies. In our review, we sought to include interventions
acteristics between individuals compared with some other where the child played an active role during goal-directed
conditions.98,99 The extent and combination of motor im- activities, following the main TOT principles.9 As child-
pairments, including muscle tone, movement control, and generated goal-directed activities are less frequently imple-
coordination, differ significantly from one child to another. mented in children with severe mobility limitations, our
Additionally, factors such as cognitive function, sensory im- results should be interpreted with caution in this popula-
pairments, communication abilities, and associated medi- tion. This is particularly relevant considering that nearly all
cal conditions contribute to the vast array of characteristics the studies included involved children functioning with CP
observed within the population with CP.100,101 Future stud- classified in GMFCS levels I to III. Future systematic reviews
ies with consistent reporting of outcomes, consistent data and robust RCTs are encouraged to address these gaps.
collection, and information about individual participants'
characteristics are necessary, preferably following standard
guidelines. Single-subject studies may be a pilot alternative C ONC LUSION
to understand this variability, potentially helping future
RCTs to select more representative outcomes and to recruit Task-oriented mobility training through treadmill training,
more homogeneous samples.102 virtual reality, and functional training potentially improves
EFFICACY AND THRESHOLD DOSE OF INTENSIVE TRAINING TARGETING MOBILITY FOR

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92. Ryan JM, Cassidy EE, Noorduyn SG, O'Connell NE. Exercise Appendix S1: Databases search strategies.
interventions for cerebral palsy. Cochrane Database Syst Rev. Appendix S2: Mobility assessments considered for the
2017;2017(6). review.
93. Liang X, Tan Z, Yun G, Cao J, Wang J, Liu Q, et al. Effectiveness
Appendix S3: Study methodology details.
of Exercise Interventions for Children With Cerebral Palsy: a
Systematic Review and Meta-A nalysis of Randomized Controlled Appendix S4: Weighted bar plots of the distribution of risk-
Trials. J Rehabil Med. 2021;53(4):1–10. of-bias judgements of included studies.
94. Carr JH, Shepherd RB. A Motor Learning Model for Stroke Appendix S5: Feasibility results.
Rehabilitation. Physiother (United Kingdom) [Internet]. Appendix S6: Detailed outcomes on mobility assessments.
1989;75(7):372–80. Available from: https://doi.org/10.1016/S0031-
Appendix S7: Sensitivity analysis.
9406(10)62588-6
95. Taghizadeh A, Webster KE, Bhopti A, Carey L, Hoare B. Are they Appendix S8: Threshold dose results.
really motor learning therapies? A scoping review of evidence- Figure S1: Study flow diagram.
based, task- focused models of upper limb therapy for chil- Table S1: Study design and sample characteristics.
dren with unilateral cerebral palsy. Disabil Rehabil [Internet]. Table S2: Experimental and control interventions.
2023;45(9):1536–48. Available from: https://doi.org/10.1080/0 9638
288.2 022.2 063414
96. Beckers LWME, Geijen MME, Kleijnen J, Rameckers EAA,
Schnackers MLAP, Smeets RJEM, et al. Feasibility and effective-
ness of home-based therapy programmes for children with cerebral How to cite this article: Sudati IP, Sakzewski L,
palsy: A systematic review. BMJ Open. 2020;10(10):1–52. Fioroni Ribeiro da Silva C, Jackman M, Haddon M,
97. Bowen DJ, Kreuter M, Spring B, Linnan L, Weiner D, Bakken Pool D, et al. Efficacy and threshold dose of intensive
S, et al. How We Design Feasibility Study. Am J Prev Med. training targeting mobility for children with cerebral
2009;36(5):452–7.
palsy: A systematic review and meta-analysis. Dev
98. Burgess A, Reedman S, Chatfield MD, Ware RS, Sakzewski L, Boyd
RN. Development of gross motor capacity and mobility perfor- Med Child Neurol. 2024;00:1–16. https://doi.
mance in children with cerebral palsy: a longitudinal study. Dev org/10.1111/dmcn.16040
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Intensive Mobility Training in Cerebral Palsy

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Intensive Mobility Training in Cerebral Palsy

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Received: 9 January 2024 | Accepted: 19 June 2024

Efficacy and threshold dose of intensive training targeting

Isabella Pessóta Sudati1,2 | Leanne Sakzewski2 | Carolina Fioroni Ribeiro da Silva1 |

Dev Med Child Neurol. 2024;00:1–16. ﻿ wileyonlinelibrary.com/journal/dmcn | 1

Cerebral palsy (CP) is a group of disorders of posture and

TA BL E 1 Study design and sample characteristics.

Experimental intervention Control intervention

Sample size Sample size

Experimental intervention Control intervention

Sample size Sample size

Ages are presented in decimal years as presented in original studies.

Summary of studies A total of 11 studies investigated the effectiveness of tread-

Summary of effectiveness findings Virtual reality

Virtual reality was effective in improving cadence com-

Five studies investigated the effectiveness of cycling train-

A total of 26 studies were included under this cate-

TA BL E 2 Experimental and control interventions.

Reference Content Intervention parameters

Reference Content Intervention parameters

Category: functional training versus control

6. Jackman M, Sakzewski L, Morgan C, Boyd RN, Brennan SE,

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Dev Med Child Neurol. 2024;00:1–16. wileyonlinelibrary.com/journal/dmcn | 1