Open access Protocol

How does the intensity of physical

BMJ Open: first published as 10.1136/bmjopen-2019-036630 on 19 July 2020. Downloaded from http://bmjopen.bmj.com/ on June 29, 2022 by guest. Protected by copyright.
therapy affect the Gross Motor Function
Measure (GMFM-66) total score in
children with cerebral palsy? A
systematic review protocol
Mary Rahlin  ‍ ‍,1 Burris Duncan,2 Carol L Howe,3 Heidi L Pottinger2

To cite: Rahlin M, Duncan B, ABSTRACT

Howe CL, et al. How does Strengths and limitations of this study
Introduction  Intensive physical therapy (PT) interventions
the intensity of physical administered to children with cerebral palsy (CP) have
therapy affect the Gross Motor ►► The broad definition of physical therapy intervention
received a significant amount of attention in published
Function Measure (GMFM-66) used in this systematic review will allow for an ap-
literature. However, there is considerable variability in
total score in children with praisal of a large body of research.
cerebral palsy? A systematic therapy intensity among studies and notable lack of
►► This systematic review will use rigorous PRISMA-­P
review protocol. BMJ Open information on optimal intervention dosing. This makes it
guidelines to investigate which interventions admin-
2020;10:e036630. doi:10.1136/ difficult for clinicians to use evidence to inform practice.
istered at what dose, and at what age may result
bmjopen-2019-036630 Many studies use the Gross Motor Function Measure
in the most functional gain in children with cerebral
(GMFM-66) to assess functional progress in children with
►► Prepublication history and palsy of different levels of severity.
CP. The purpose of this systematic review will be to identify
additional material for this ►► Title and abstract screening, as well as the full-­text
paper are available online. To the GMFM-66 change score reported in published studies,
article screening in this systematic review were
view these files, please visit with outcomes based on intervention intensity. Whether
performed by two independent reviewers, with dis-
the journal online (http://​dx.​doi.​ the type of PT intervention, child’s age, and Gross Motor
agreements resolved by consensus.
org/​10.​1136/​bmjopen-​2019-​ Function Classification System level influence the GMFM-
►► During this systematic review, data extraction, risk
036630). 66 scores will be also assessed.
of bias assessment and evaluation of the quality of
Methods and analysis  This systematic review protocol
Received 23 December 2019 evidence will be performed by two independent re-
was developed based on the Preferred Reporting Items
Revised 31 March 2020 viewers and verified by a third reviewer.
for Systematic Reviews and Meta-­Analyses Protocols
Accepted 11 June 2020 ►► It is expected that the heterogeneity of reviewed
(PRISMA-­P) 2015 checklist. In March 2018, nine databases
research reports will preclude the performance of
(PubMed, Ovid MEDLINE, Cochrane Library, Embase,
meta-­analyses of data and may make the study
Scopus, Web of Science, CINAHL, ​ClinicalTrials.​gov, and
groupings and related comparisons difficult.
REHABDATA) were searched for controlled clinical trials
© Author(s) (or their and single-­subject design studies of PT interventions
employer(s)) 2020. Re-­use of any kind and intensity that used the GMFM-66 as interventions varies in its level and quality, as
permitted under CC BY-­NC. No an outcome measure for children with CP, age up to 18 do the PT frequency and duration parame-
commercial re-­use. See rights years. Two authors independently reviewed the titles and
and permissions. Published by ters. Intensive interventions administered to
abstracts and arrived at consensus on paper selection for
BMJ.
a full-­text review. The same process was used for a full-­
children with CP have received a significant
1
Department of Physical text article screening based on further detailed inclusion amount of attention in the published litera-
Therapy, Rosalind Franklin criteria, with a final selection made for those suitable for ture. However, there is considerable variability
University of Medicine and both in the type of therapeutic intervention
data extraction. Prior to commencement of data extraction,
Science, North Chicago, Illinois,
all searches will be updated, and new results re-­screened. and the intensity with which it is administered
USA
2
Department of Health Ethics and dissemination  This study will involve a and at what age,1 and a notable lack of informa-
Promotion Sciences, Mel and systematic review of published articles and no primary tion on the optimal intervention dosing.2 3 This
Enid Zuckerman College of data collection. Therefore, no ethical approval will be makes it difficult for clinicians to use evidence
Public Health, University of necessary. Results will be disseminated in a peer-­reviewed to inform practice and to define the ‘standard
Arizona, Tucson, Arizona, USA publication and presented at scientific conferences. of care’ for this patient population. The ratio-
3
Health Sciences Library, PROSPERO registration number  CRD42020147669
University of Arizona, Tucson, nale for early intensive therapy and examples
Arizona, USA of related studies are provided below.
INTRODUCTION
Correspondence to
Dr Mary Rahlin; Physical therapy (PT) for children with cere-
​Mary.​Rahlin@​rosalindfranklin.​ bral palsy (CP) includes a wide variety of
edu interventions. Evidence supporting these

Rahlin M, et al. BMJ Open 2020;10:e036630. doi:10.1136/bmjopen-2019-036630 1

Open access

Rationale for PT started early and administered with intensity et al.13 Changes are maximised and have long-­term reten-

BMJ Open: first published as 10.1136/bmjopen-2019-036630 on 19 July 2020. Downloaded from http://bmjopen.bmj.com/ on June 29, 2022 by guest. Protected by copyright.
The rationale for an intensive series of active, repetitive, tion if rehabilitation is repetitive, intensive, and meaningful
task-­
specific therapies is based on what is known about or skill oriented. For example, the cortical map represen-
brain plasticity as seen in animal studies,4 rehabilitation tation of the index finger of a Braille reader is larger than
interventions in adult stroke survivors5 and investigations in that represented by the adjacent fingers and is larger than
children with unilateral CP, often secondary to a ‘perinatal on the ipsilateral cortex. A person with bilateral upper
stroke’.6 7 Cortical reorganisation is influenced by several extremity amputation who has learnt to use his right great
factors: the precise location and size of the lesion, the age toe to paint or sculpt shows an enlargement of the cortical
at which the injury occurred, and the nature and extent of area represented by the right great toe.14
the rehabilitative training.4 Some basic principles are pertinent15 to the argument
Reorganisation can occur in one of three ways: by recruit- for early, intensive intervention: (1) There are critical
ment of undamaged neurons adjacent to the injured times during neural development when a certain task is
neurons, by recruitment of neurons from supplemental most easily learnt; (2) Reorganisation and reprogramming
non-­primary motor areas, or by stimulation of ipsilateral of neural tissue is use dependent (‘use it or lose it’), and
neurons.4 If the lesion involves a small area, the imme- repetitive active movement has the greatest potential for
diate adjacent territory is reprogrammed for the lost stimulating neural growth; and (3) A young brain is more
function. If the lesion is larger and involves the adjacent adaptable than an older brain.15
territory, reprogramming may recruit premotor cortical
areas. Surgical lesions in newborn monkeys initially result Examples of evidence for intensive intervention administered
in motor dysfunction, but function gradually returns early
as the areas adjacent to the damaged ones are repro- In 2010, Arpino et al16 reported on a meta-­analysis of inten-
grammed to assume the function of damaged neurons. sive PT in children with CP and found only three studies
If the lesion is very large, the intact opposite hemisphere that satisfied their criteria for a randomised clinical trial
may be recruited.4 The latter situation is most dramatic in (RCT), which included having the word ‘intensive’ in the
the young child who has undergone a hemispherectomy as title, involving therapy frequency greater than three times
radical treatment for uncontrolled seizures.8 Within days, a week, and using the Gross Motor Function Measure
the child is walking and shows only mild signs of hemipa- (GMFM)17 as the outcome measure.16 Bower et al18 19 eval-
resis. This is probably the result of intact ipsilateral connec- uated 56 children between 3 and 12 years of age, Gross
tions but also of the removal of abnormal discharges from Motor Function Classification System (GMFCS) level III or
the contralateral dysfunctional hemisphere.8 greater, all treated by a different therapist. These children
The pathophysiology of an adult stroke is very similar to showed a trend for improvement, but it did not reach statis-
a perinatal stroke that has resulted in hemiparetic CP. Even tical significance.18 19 The RCT by Tsorlakis et al20 involved
in the older brain, repetitive motor skill–directed rehabil- 34 children between 3 and 14 years of age with mild to
itation promotes brain plasticity, can restore some func- moderate CP (GMFCS levels I–III). There was a statistically
tion, and is represented by an enlarged area of the motor significant difference found for the group that received the
cortex.9 With no rehabilitation, there is scant improvement most intensive therapy (50 min sessions, 5 times a week,
in function and no increase in the cortical map representa- for 16 weeks).20 Shamir et al21 used a cross-­over design to
tion. Restriction of movement in the strong arm and hand evaluate 10 patients, 12–22 months of age, and reported a
of a stroke survivor for as little as 10 days improves function gain of 7.8% on the GMFM for those receiving an inten-
of the paretic arm, and a corresponding enlargement of the sive intermittent approach compared with a gain of 1.2% in
cortical representation of that upper extremity is observed. those who received the standard of care therapy. The inten-
In contrast, non-­use of the paretic limb results in a decrease sive intermittent therapy was administered four times per
in the corresponding cortical representation.9 Similar find- week for 90 min in week 1, followed by a 3-­week rest period.
ings have been reported in children with unilateral CP, with The standard of care therapy included one 90 min session
constraint-­induced therapy administered for just 6 hours a per week.21
day for 10 days.10
The fact that a young brain is more adaptable, with Rationale for targeting the GMFM-66 change score in this
greater neural plasticity potential than an older brain, is review
due to several factors.10 11 Because there is less myelin in Many of the published studies of PT interventions use the
the young brain, the neurons have a better potential to GMFM17 to assess progress in gross motor functional skills
repair themselves.11 This, combined with the abundance of in children with CP. The GMFM-66 is a version of this instru-
trophic factors that stimulate nerve growth, supports neural ment that is scored using a Gross Motor Ability Estimator
plasticity in the younger compared to an older brain.10 11 (GMAE), a computer program that yields an interval-­level
Cortical reorganisation based on the principles of motor total GMFM-66 score based on the individual test item
learning leads to sprouting of dendrites, formation of new scores entered by the examiner.17 Intervention intensity can
synapses, alternation in existing synapses, and production be defined as a combination of intervention frequency and
of neurochemicals.12 The type of rehabilitative therapies duration of therapy sessions provided over a specific period
that will induce neural reorganisation was reviewed by Arya of time.22 23 Conducting a review of literature to identify the

2 Rahlin M, et al. BMJ Open 2020;10:e036630. doi:10.1136/bmjopen-2019-036630

 Open access

GMFM-66 change score reported in published studies of PT Search strategy

BMJ Open: first published as 10.1136/bmjopen-2019-036630 on 19 July 2020. Downloaded from http://bmjopen.bmj.com/ on June 29, 2022 by guest. Protected by copyright.
intervention provided to children with CP, with outcomes An information specialist (CLH) searched the following
based on PT intensity, may serve as a useful step toward databases from the year 2002, when the GMFM-66 was
determining which interventions administered at what introduced, to the date the searches were run (14–15
dose and at what age may result in the most gross motor March 2018): Ovid/MEDLINE, Elsevier/Embase, Else-
gain in children functioning at different GMFCS levels. It vier/Scopus, Wiley/Cochrane Library, Clarivate/Web of
is important to note that a GMFM-66 score is a measure of Science (WOS), EBSCO/Cumulative Index of Nursing
motor capacity (what the child is capable of doing) and and Allied Health Literature (CINAHL), C ​ linicalTrials.​gov
not a measure of motor performance that is defined by a and National Rehabilitation Information Center/REHAB-
combination of the child’s observed physical activity and DATA. An English-­language filter was applied.
sedentary behaviour.24 25 Furthermore, changes in motor The Ovid MEDLINE search strategy, on which the
capacity after an intensive intervention may not be neces- other database search strategies were based, is presented
sarily accompanied by changes in motor performance.24 26 in online supplementary appendix. All records identified
Thus, the GMFM-66 change score targeted by this review through the database searches were exported to the refer-
will not reflect the effects of PT intervention on activity ence managing software EndNote versions X8–X9 (Clari-
performance. vate Analytics, Philadelphia, PA, USA) which was used to
document and delete the duplicate records.
Objectives Two independent reviewers (MR and BD) screened
The purpose of this systematic review will be to identify the all titles and abstracts for relevance, with disagreements
GMFM-66 change score reported in published studies of PT resolved by consensus. Full texts of all references that
interventions provided to children with CP, with outcomes met the screening eligibility were similarly independently
based on intervention intensity. For the purposes of this screened for inclusion by MR and BD according to the
review, intensive protocols will be defined as those admin- following inclusion/exclusion criteria, with disagreements
istered at least three times per week, and their outcomes, resolved by consensus.
described as the GMFM-66 change score, will be compared
to those administered less frequently. Data on the dura- Inclusion criteria
tion of therapy sessions and the length of time over which 1. GMFM-66 used as an outcome measure.
the intervention was provided will be extracted and added 2. GMFM-66 total score reported.
to these comparisons if specific related groupings can be 3. Children of any age up to 18 years who had CP of any
identified. The review will also assess how the type of PT type and functional level.
intervention, as well as the child’s age and GMFCS level may 4. Completed controlled clinical trials of PT intervention
influence the functional outcome of intervention measured of any kind and any intensity, with the control group
by the GMFM-66. This systematic review will be conducted receiving any of the following:
to answer the following specific questions: –– No intervention.
1. Do PT interventions provided to children with CP with –– A different type of PT intervention.
a frequency of three times per week or greater result –– The same PT intervention of different frequency or
in a greater improvement in gross motor function, as supplemented with a medical intervention.
measured by the change in GMFM-66 total score, than –– An alternative or complementary intervention.
PT interventions provided less frequently? 5. Completed single-­ subject research design studies
2. Are greater GMFM-66 change scores reported in stud- (SSRDs) of PT intervention, of any kind and inten-
ies of PT interventions conducted in children with CP sity, with effects replicated across at least three sub-
younger than 5 years of age compared to the GMFM- jects.
66 change scores of those who are 5 years of age and 6. Only English-­language publications.
older? 7. Year of publication during or after 2002.
3. Are children with mild to moderate CP (GMFCS levels
Exclusion criteria
I–III) more responsive to PT as indicated by the report-
1. Children who developed typically or had conditions
ed change in GMFM-66 total score than children with
other than CP.
more severe CP (GMFCS levels IV and V)?
2. Children identified as being at risk for CP.
4. Which PT interventions produce the highest GMFM-
3. Individuals with CP who were older than 18 years of
66 change scores, as indicated by the results of pub-
age.
lished studies?
4. Non-­experimental research
–– Correlation studies
METHODS AND ANALYSIS –– Reliability studies
Design –– Review papers
This systematic review protocol was developed based on –– Survey studies
the Preferred Reporting Items for Systematic Reviews and 5. Non–English-­language publications.
Meta-­Analyses Protocols (PRISMA-­P) 2015 checklist.27 6. Published protocols, results not yet reported.

Rahlin M, et al. BMJ Open 2020;10:e036630. doi:10.1136/bmjopen-2019-036630 3

Open access

Table 1  Data extraction variables

BMJ Open: first published as 10.1136/bmjopen-2019-036630 on 19 July 2020. Downloaded from http://bmjopen.bmj.com/ on June 29, 2022 by guest. Protected by copyright.
Participants Intervention Comparators Outcomes
Age Specific PT intervention used in In group comparison studies GMFM-66 total score
the study (controlled clinical trials,
randomised and non-­randomised)
►► <5 years Frequency of intervention ►► No intervention ►► Initial
►► >5 years ►► <3 times per week ►► A different type of PT ►► Final
intervention
Severity of cerebral palsy ►► ≥3 times per week ►► The same PT intervention ►► Change
of different frequency or
supplemented with a medical
intervention
►► Mild to moderate (GMFCS Duration of PT sessions (min) ►► An alternative or  
levels I–III) complementary intervention
►► Severe (GMFCS levels IV–V) Length of time intervention was In SSRDs, participants serve as  
administered (weeks) their own controls
  Adherence to protocol (% of the    
time)

GMFCS, Gross Motor Function Classification System; GMFM-66, Gross Motor Function Measure; PT, physical therapy; SSRD, single-­subject
research design.

Prior to commencement of data extraction, all searches ►► Duration of PT sessions and the length of time (weeks)
will be updated and new results re-­screened. While we did over which the intervention was administered.
not initially plan for a two-­step search and selection process, These PT intervention parameters contribute to its
it soon became evident that the overall time required to intensity.22 23 However, defining intensive protocols
reach the data extraction stage would be considerably longer based on all three related variables (frequency, dura-
than initially projected. In order to maintain currency and tion and length of time over which the intervention was
have our review be as up to date as possible, we realised we administered) may be difficult because of the antici-
would need to rerun the searches and have included that pated high variability in intervention parameters among
step in this protocol. Citations from relevant review articles
the studies. Nevertheless, if specific related groupings
and citations to and from all initially included articles will
of published studies can be identified, the results of
be searched and screened as well.
this review related to intervention intensity may be
Data extraction strengthened.
The variables that will be sought for group comparison ►► The age of the child defined as ‘younger than 5 years’
studies and SSRDs are listed in table 1 for each of the or ‘5 years and older’.
PICO items (Participants, Intervention, Comparators, and This variable was prioritised based on the current
Outcomes). Data extraction will be completed by two inves- understanding of brain plasticity, as dormant neurons are
tigators (BD, HLP), independently of each other, and veri- better stimulated and activated in ‘younger’ versus ‘older’
fied by the third investigator (MR) who will lead a discussion brains.10 15
of any identified discrepancies to reach consensus. ►► The severity of CP defined by the GMFCS levels I, II
Outcomes and prioritisation or III (mild to moderate) or levels IV and V (severe).
Primary outcome An assumption has been made that children with CP
The primary outcome will be the change in total of greater severity may have a larger-­sized brain injury
GMFM-66 scores in children of any age up to 18 years, or a different precise area of injury.4 As discussed in
with a diagnosis of CP of any severity, who have had any the Introduction section of this paper, based on the
type of PT with a frequency equal to or greater than three current understanding of brain plasticity, the size and
times per week, compared to a frequency of fewer than area of the injury determines the type of potential
three times per week. This was prioritised based on the reprogramming.4
current understanding of brain plasticity, as dormant
►► Specific PT intervention used in the study.
neurons are best stimulated and activated or recruited by
As stated previously, there is a wide variety of PT inter-
the frequency of active movement.10 28
ventions that are used in children with CP. Identifying
Additional outcomes which of these interventions have been documented to
We will also determine if the change in the GMFM-66 produce higher GMFM-66 change scores may provide
total scores based on intervention frequency is influenced valuable evidence that can be used to inform clinical
by the following variables: practice.

4 Rahlin M, et al. BMJ Open 2020;10:e036630. doi:10.1136/bmjopen-2019-036630

 Open access

Risk of bias in individual studies Data synthesis

BMJ Open: first published as 10.1136/bmjopen-2019-036630 on 19 July 2020. Downloaded from http://bmjopen.bmj.com/ on June 29, 2022 by guest. Protected by copyright.
Group comparison studies Group comparison studies assigned a ‘low’ and ‘very low’
To assess the risk of bias in group comparison studies, we risk of bias rating, and the SSRDs rated as ‘low risk’ will be
will use the Physiotherapy Evidence Database (PEDro) included in the data synthesis. It is anticipated that data
scale to rate the methodological quality of RCTs that eval- may not be appropriate for quantitative synthesis because
uate PT interventions.29–32 Maher et al31 demonstrated a of the expected heterogeneity of the reviewed studies.
fair to good reliability of the PEDro total score. In addi- Therefore, the majority or the entire report will be a
tion, de Morton32 found the PEDro scale to be a valid narrative synthesis. However, if a subset or several subsets
instrument for assessing methodological quality of clin- of the studies provide homogeneous data, we will perform
ical trials, and demonstrated that the PEDro total score partial meta-­analyses of that data. We recognise that phys-
can be considered interval-­level data, which warrants the ical therapy for children with CP includes a wide variety of
use of parametric methods of statistical analysis. interventions. Therefore, we anticipate that data appro-
The PEDro scale consists of 11 items rated on a dichot- priate for meta-­analyses may include so-­called ‘hands-­on’
omous scale (yes/no), with each ‘yes’ answer, except therapeutic approaches that involve direct handling of
for item 1, assigned a score of 1, and each ‘no’ answer the child by the therapist or ‘hands-­off,’ equipment-­based
assigned a score of 0.29 30 The total score is calculated by gait training interventions. Even then, we expect to find
adding the individual item scores for items 2–11. Item 1 a high level of heterogeneity of data within each of these
pertains to the external validity of the clinical trial and is two groups of studies.
not used to calculate the PEDro score.29 30
Confidence in cumulative evidence
SSRD studies The appropriate level of evidence (1 through 5) for
To assess the methodological quality of SSRDs, we will each of the group comparison studies will be assigned
use the rating scale developed by Romeiser Logan et according to the Oxford Centre for Evidence-­ Based
al33 specifically for single-­subject design research. The Medicine.36 The level of evidence of SSRDs will be deter-
scale authors reported a 75% agreement in obtaining mined using levels I through V proposed specifically for
the total score, which was comparable with the scales this type of studies by Romeiser Logan et al.33 Two inves-
that are used to assess the methodological quality of tigators (HLP, MR) will assign the levels of evidence to
group-­design studies. The SSRD rating scale consists of group comparison studies independently of each other,
and the third investigator (BD) will verify their findings
14 items scored on a dichotomous scale (yes/no), with
and lead the discussion of any identified discrepancies to
a ‘no’ answer receiving a score of 0 and a ‘yes’ answer
reach consensus. Similarly, two investigators (BD, HLP)
assigned one point except for items 5 and 8. Each of
will assign the levels of evidence to the SSRDs, to be veri-
these two items represents a two-­part question, and a
fied by the third investigator (MR) who will lead a discus-
‘yes’ answer obtained for each part is assigned a score of
sion of any identified discrepancies to reach consensus.
0.5. The total score is obtained by adding the individual
item scores.33
Patient and public involvement
The development of this systematic review protocol was
Other bias informed by the authors’ clinical practice and academic
All studies will be assessed for whether participants’ evalu- and research experience gained from working with chil-
ations using the GMFM-66 were performed following the dren with cerebral palsy and their families. No patients
specifications outlined in the test manual, including the will be involved in this systematic review.
use of the GMAE.21 In addition, the number of GMFM-66
items used to obtain the total score and whether this infor- Ethics and dissemination
mation was reported in the reviewed studies will be taken Because this study will involve a systematic review of
into account as an important quality criterion. Avery et already published articles, and no primary data collec-
al34 found that a valid estimate of the child’s gross motor tion will take place, no ethical approval is necessary.
function could be made by testing only 13 GMFM-66 This systematic review protocol was registered in the
items, which led to the development of the short forms International Prospective Register of Systematic Reviews
of this test.35 Nevertheless, the GMFM-66 authors recom- (PROSPERO) on June 19, 2020, registration number
mend testing as many items as possible to obtain the most CRD42020147669. Results will be submitted for publica-
accurate total score, especially when measuring change tion to a peer-­reviewed journal and presented at scientific
over time is the main priority.17 conferences.
Two investigators (MR, BD) will complete the risk of bias
assessments for group comparison studies independently Contributors  BD initiated the idea for the systematic review and MR heads the
of each other, and the third investigator (HLP) will verify research team. MR and BD developed the selection criteria and completed the
initial screening. CLH provided guidance, developed the search strategies and
their findings and lead the discussion of any identified
conducted the database searches. MR, BD, HLP and CLH developed the protocol. All
discrepancies to reach consensus. Similarly, BD and HLP four authors participated in the protocol manuscript writing, provided feedback to
will assess and MR will verify the risk of bias in the SSRDs. all, and approved its final version.

Rahlin M, et al. BMJ Open 2020;10:e036630. doi:10.1136/bmjopen-2019-036630 5

 Open access

Funding  BD and HLP are supported by a grant from the Eunice Kennedy Shriver 14 Nolte J. The human brain: an introduction to its functional anatomy.

BMJ Open: first published as 10.1136/bmjopen-2019-036630 on 19 July 2020. Downloaded from http://bmjopen.bmj.com/ on June 29, 2022 by guest. Protected by copyright.
National Institute of Child Health and Human Development (NICHD), National 6th ed. Philadelphia, PA: Elsevier, 2008.
Institutes of Health (NIH), Project number R01 HD079498, and receive institutional 15 Kolb B, Gibb R. Critical periods for functional recovery after cortical
injury during development. In: Lomber S, Eggermont J, eds.
support from Mel and Enid Zuckerman College of Public Health, University of
Reprogramming the cerebral cortex: plasticity following central
Arizona. MR receives institutional support from Rosalind Franklin University of and peripheral lesions. New York, NY: Oxford University Press,
Medicine and Science (RFUMS), North Chicago, IL. CLH receives institutional 2006: 297–307.
support from the University of Arizona Health Sciences Library. No designated 16 Arpino C, Vescio MF, De Luca A, et al. Efficacy of intensive versus
funding has been received specifically for this project. nonintensive physiotherapy in children with cerebral palsy: a meta-­
analysis. Int J Rehabil Res 2010;33:165–71.
Competing interests  None declared. 17 Russell DJ, Rosenbaum PL, Wright M, et al. Gross Motor Function
Patient and public involvement  Patients and/or the public were not involved in Measure (GMFM-66 & GMFM-88) User’s Manual. 2nd. Devon: Mac
the design, or conduct, or reporting, or dissemination plans of this research. Keith Press, 2013.
18 Bower E, McLellan DL, Arney J, et al. A randomised controlled trial
Patient consent for publication  Not required. of different intensities of physiotherapy and different goal-­setting
procedures in 44 children with cerebral palsy. Dev Med Child Neurol
Provenance and peer review  Not commissioned; externally peer reviewed. 1996;38:226–37.
Open access  This is an open access article distributed in accordance with the 19 Bower E, Michell D, Burnett M, et al. Randomized controlled trial
Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which of physiotherapy in 56 children with cerebral palsy followed for 18
permits others to distribute, remix, adapt, build upon this work non-­commercially, months. Dev Med Child Neurol 2001;43:4–15.
20 Tsorlakis N, Evaggelinou C, Grouios G, et al. Effect of intensive
and license their derivative works on different terms, provided the original work is neurodevelopmental treatment in gross motor function of children
properly cited, appropriate credit is given, any changes made indicated, and the use with cerebral palsy. Dev Med Child Neurol 2004;46:740–5.
is non-­commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. 21 Shamir M, Dickstein R, Tirosh E. Intensive intermittent physical
therapy in infants with cerebral palsy: a randomized controlled pilot
ORCID iD study. Isr Med Assoc J 2012;14:737–41.
Mary Rahlin http://o​ rcid.​org/​0000-​0001-​5126-​4338 22 Rahlin M. An individualized intermittent intensive physical therapy
schedule for a child with spastic quadriparesis. Physiother Theory
Pract 2011;27:512–20.
23 Rahlin M. Therapy frequency, duration, and intensity issues. In:
Physical therapy for children with cerebral palsy: an evidence-­based
REFERENCES approach. Thorofare, NJ: SLACK Incorporated, 2016: 275–82.
1 Bailes AF, Succop P. Factors associated with physical therapy 24 Halma E, Bussmann JBJ, van den Berg-­Emons HJG, et al.
services received for individuals with cerebral palsy in an outpatient Relationship between changes in motor capacity and objectively
pediatric medical setting. Phys Ther 2012;92:1411–8. measured motor performance in ambulatory children with spastic
2 Gannotti ME, Christy JB, Heathcock JC, et al. A path model for cerebral palsy. Child Care Health Dev 2020;46:66–73.
evaluating dosing parameters for children with cerebral palsy. Phys 25 Bussmann JBJ, van den Berg-­Emons RJG. To total amount of
Ther 2014;94:411–21. activity and beyond: perspectives on measuring physical behavior.
3 Kolobe THA, Christy JB, Gannotti ME, et al. Research Summit III Front Psychol 2013;4:463.
proceedings on dosing in children with an injured brain or cerebral 26 Duran I, Stark C, Martakis K, et al. Reference centiles for the gross
palsy: executive summary. Phys Ther 2014;94:907–20. motor function measure and identification of therapeutic effects in
4 Rouiller EM, Wannier T, Schmidlin E, et al. Reprogramming the motor children with cerebral palsy. J Eval Clin Pract 2019;25:78–87.
cortex for functional recovery after neonatal or adult unilateral lesion 27 Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for
of the corticospinal system in the macaque monkey. In: Lomber S, systematic review and meta-­analysis protocols (PRISMA-­P) 2015:
Eggermont J, eds. Reprogramming the cerebral cortex: plasticity elaboration and explanation. BMJ 2015;350:g7647.
following central and peripheral lesions. New York, NY: Oxford 28 Kleim JA, Jones TA. Principles of experience-­dependent neural
University Press, 2006: 309–24. plasticity: implications for rehabilitation after brain damage. J Speech
5 Hallett M. Plasticity of the human motor cortex and recovery from Lang Hear Res 2008;51:225–39.
stroke. Brain Res Brain Res Rev 2001;36:169–74. 29 PEDro. PEDro scale. Available: https://www.​pedro.​org.​au/​wp-​
6 Sterling C, Taub E, Davis D, et al. Structural neuroplastic change content/​uploads/​PEDro_​scale.​pdf [Accessed 2 Jun 2019].
after constraint-­induced movement therapy in children with cerebral 30 PEDro. Frequently asked questions. PEDro website. Available:
palsy. Pediatrics 2013;131:e1664–9. https://www.​pedro.​org.​au/​english/​faq/ [Accessed 2 Jun 2019].
7 Charles JR, Gordon AM. A repeated course of constraint-­induced 31 Maher CG, Sherrington C, Herbert RD, et al. Reliability of the PEDro
movement therapy results in further improvement. Dev Med Child scale for rating quality of randomized controlled trials. Phys Ther
Neurol 2007;49:770–3. 2003;83:713–21.
8 de Bode S, Mathern GW, Bookheimer S, et al. Locomotor training 32 de Morton NA. The PEDro scale is a valid measure of the
remodels fMRI sensorimotor cortical activations in children methodological quality of clinical trials: a demographic study. Aust J
after cerebral hemispherectomy. Neurorehabil Neural Repair Physiother 2009;55:129–33.
2007;21:497–508. 33 Romeiser Logan L, Hickman RR, Harris SR, et al. Single-­subject
9 Liepert J, Bauder H, Wolfgang HR, et al. Treatment-­iInduced cortical research design: recommendations for levels of evidence and quality
reorganization after stroke in humans. Stroke 2000;31:1210–6. rating. Dev Med Child Neurol 2008;50:99–103.
10 Johnston MV. Plasticity in the developing brain: implications for 34 Avery LM, Russell DJ, Raina PS, et al. Rasch analysis of the gross
rehabilitation. Dev Disabil Res Rev 2009;15:94–101. motor function measure: validating the assumptions of the Rasch
11 Boghdadi AG, Teo L, Bourne JA. The involvement of the myelin-­ model to create an interval-­level measure. Arch Phys Med Rehabil
associated inhibitors and their receptors in CNS plasticity and injury. 2003;84:697–705.
Mol Neurobiol 2018;55:1831–46. 35 Avery LM, Russell DJ, Rosenbaum PL. Criterion validity of
12 Mulder T, Hochstenbach J. Adaptability and flexibility of the human the GMFM-66 item set and the GMFM-66 basal and ceiling
motor system: implications for neurological rehabilitation. Neural approaches for estimating GMFM-66 scores. Dev Med Child Neurol
Plast 2001;8:131–40. 2013;55:534–8.
13 Arya KN, Pandian S, Verma R, et al. Movement therapy induced 36 OCEBM Levels of Evidence Working Group. The Oxford 2011 Levels
neural reorganization and motor recovery in stroke: a review. J of Evidence. Oxford Centre for Evidence-­Based Medicine website.
Bodyw Mov Ther 2011;15:528–37. Available: http://www.​cebm.​net/ [Accessed 26 Jul 2019].

6 Rahlin M, et al. BMJ Open 2020;10:e036630. doi:10.1136/bmjopen-2019-036630