Effects of upper extremity surgery on activities and participation of children with cerebral palsy: a systematic review

Aim To evaluate and synthesize the evidence for effects of upper extremity surgery (UES) on activities and participation of children and adolescents with cerebral palsy (CP). Method The databases MEDLINE, Embase, and PsycINFO were searched for publications up to September 2018. Studies included were comparative studies with or without concurrent comparison groups or case series with pretest/posttest outcomes with a minimal sample size of 10 participants; those that reported the effects of UES with a follow‐up time of at least 5 months; those including patients diagnosed with CP aged up to 20 years; and those that used a validated activity‐based instrument. Risk of bias was assessed using the ROBINS‐I (Risk Of Bias In Non‐randomised Studies ‐ of Interventions) tool and quality assessment was performed using the Grading of Recommendations Assessment, Development and Evaluation. Results Twelve studies, involving 310 children and adolescents, were included. The ability and perception of the patient to use the hand(s) and perform activities (measured with the Shriners Hospital Upper Extremity Evaluation, Assisting Hand Assessment, and House Functional Classification) improved significantly after UES. The quality of evidence was very low for each of the activity outcomes of interest. Interpretation The very low evidence prohibits recommendations on the use of UES to guide clinical practice. More high‐quality comparative studies are needed to obtain better insight into the effects of UES on activities and participation. What this paper adds Low quality of evidence for effects of upper extremity surgery (UES) on activities and participation. Limited evidence for improvement in activities and participation after UES.

Children and adolescents with cerebral palsy (CP) represent the largest diagnostic group treated in paediatric rehabilitation. The upper limbs are often affected with significant wrist and hand involvement. 1 The abnormal upper limb tone and hand posture, most frequently forearm pronation, thumb adduction, and/or flexion with limited wrist extension, have an impact on the ability to use the affected hand and both hands together. 2 One of the treatment options for improving functional performance is upper extremity surgery (UES). Unfortunately, there is a substantial emphasis in the medical literature reporting outcomes on the effect of UES relating to the 'body functions and structures' component of the International Classification of Functioning, Disability and Health for Children and Youth: 3 i.e. motor outcomes, active and passive range of motion and spasticity reduction, position of the hand, appearance, and grip function. 4 Less clear and less reported is the effect of UES on the International Classification of Functioning, Disability and Health for Children and Youth component of 'activities and participation'. 3 UES aims to improve muscle balance and hand posture, by releasing or lengthening spastic muscles, transferring tendons, and stabilizing joints. Commonly used procedures are: (1) release of pronator teres muscle to facilitate forearm supination; 5,6 (2) release or transfer of the flexor carpi ulnaris tendon to facilitate or increase wrist extension for functional grip purposes; 7 and (3) correction of a thumbin-palm deformity, preferably by adductor pollicis muscle slide 8 combined with extensor pollicis longus rerouting. 9 In contrast to activity-based interventions, UES is an invasive intervention followed by immobilization in plaster for 5 to 6 weeks and then an intensive therapy programme, depending on the goals and type of surgery.
Over the past decade, more studies have used validated activity-based instruments to evaluate the effect of UES on activities: i.e. the use of the affected hand and perceived performance. The execution of activities can be assessed according to the patient's functional performance (what the patient usually does), by testing what a patient is able to do on request (capacity), or by evaluating the patient's self-perception of the ability to use the affected arm. An overview of evidence about the effect of UES on activities and participation is needed to guide medical professionals in intervention planning and to inform patients on the risks, benefits, and possible outcomes of UES on daily activities.
The aim of this systematic review was to evaluate and synthesize the evidence for the effects of UES on activities and participation in activities of children and adolescents (<20y) 3 with CP. This review will focus on two types of activity-based outcome measure: (1) functional performance outcome measures (clinical-based), which reflect the patient's performance on quantifiable tasks, classification, or questionnaire; and (2) perceived performance outcome measures (patient-reported), which reflect the perception of the patient's ability to use the hand(s) in task performance.

METHOD
This systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 10 The review has been registered in the international prospective register of systematic reviews (PROSPERO CRD42017058753).

Eligibility criteria
Published studies investigating the effect of UES in children and adolescents with CP were included if they met the following criteria: (1) They were (pseudo-)randomized controlled trials, comparative studies with concurrent comparison groups (including a non-randomized experimental trial, prospective and retrospective cohort study, case-control study, and interrupted time series with a comparison group), comparative studies without comparative individuals (including a historical control study, two or more single-arm studies, and interrupted time series without a parallel comparison group), or case series with either posttest or pretest/posttest outcomes with a minimal sample size of 10 participants (because smaller studies are associated with a very high risk of [selection] bias); (2) A validated activity-based instrument was used to measure the effect of UES on activities and participation; (3) The UES intervention was not combined with botulinum neurotoxin A injections 6 months before surgery; and (4) More than 75% of the participants were children or adolescents diagnosed with CP aged up to 20 years or, if data on the children/adolescents with CP were reported separately, to ensure that study results were generalizable to CP. Studies were excluded if no full-text was available in English.

Search strategy
The comprehensive literature search started with a reference set collected through citation analysis (cited by tracking) in Google Scholar. References in the included articles were checked and used to complete the reference set up to 45 articles. This reference set was used to derive the following major search concept combination: [cerebral palsy]

AND ([releasing/lengthening] OR {[surgery/therapy] AND [anatomic region]}).
The literature search was conducted in three electronic databases indexing health-related journals, for publication up to September 2018: MEDLINE, Embase, and PsycINFO.
The search strategy was adapted to match the controlled vocabulary and search syntax of each database (see Appendix S1 [online supporting information] for details). The search strategy was developed to maximize the sensitivity of article identification. All items in the reference set had to be retrieved by the systematic search strategy in all databases if present.
Review authors also searched reference lists of included studies and other narrative reviews, identifying no additional reference titles. All duplicates were removed. The search strategy was designed in collaboration with a clinical librarian according to the recommendations of the PRISMA guidelines. 10

Study selection
Titles and abstracts were initially screened for study eligibility/relevance by the first author (AL) with the last author (AB) screening excluded titles and abstracts to ensure that no relevant papers were omitted. After the initial identification and screening, full-text articles reporting the effect of UES in children/adolescents with CP were reviewed and independently assessed for eligibility according to the inclusion and exclusion criteria by two reviewers (AL and AB). Cases of disagreement were discussed until consensus was reached.

Data extraction
Two reviewers (AL and AB) extracted information from each included study independently and reported their findings on a data extraction sheet on the basis of the Oxford Centre for Evidence-Based Medicine Scale V2.1. 11 Disagreements were resolved by discussion between the two review authors. No authors were contacted to provide additional data.

Risk of bias in individual studies
The risk of bias for non-randomized observational interventional studies with validated outcome measures was evaluated by two reviewers (AL and AB) working independently using the ROBINS-I (Risk Of Bias In Non-What this paper adds • Low quality of evidence for effects of upper extremity surgery (UES) on activities and participation.
• Limited evidence for improvement in activities and participation after UES.
randomised Studies -of Interventions) measurement tool. 12 Each article was assessed as having low, high, or unclear risk for six criteria and is reported in the tables of characteristics of included studies (Table SI, online supporting information) and risk of bias (Table I).

Assessment of the quality of evidence
The quality of the body of evidence for each outcome was examined by two assessors (AB and AL) according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group criteria. 13 GRADE was used to summarize the body of evidence and to enable quicker interpretation of the findings of the review for clinical practice. The overall quality of evidence was determined to be high, moderate, low, or very low using a stepwise, structural methodology. This was done for outcomes of interest across the studies, as well as for the strength of recommendation for using the UES intervention. The scores were compared and disagreements were resolved by discussion and consensus.

Data synthesis
Given the heterogeneity of UES interventions (within and between studies) and reported outcomes on activities and participation, a meta-analysis could not be performed. Therefore a narrative synthesis of results is presented.

Study selection
The electronic search provided a total of 8552 citations. After adjusting for duplicates, 6501 remained. Of these, 6366 studies were discarded because, after reviewing the abstracts, it seemed that these papers were not published with a full text in English (n=603) or did not meet the criteria (n=5763). The full text of the remaining 140 citations was examined in more detail. One hundred and fourteen studies did not meet the inclusion criteria as described, mainly because of a different outcome or population and small numbers of participants. Fourteen studies were excluded because data were not presented separately or fewer than 75% of the participants were patients diagnosed with CP aged up to 20 years. Finally, a total of 12 studies were identified for inclusion in the review (Fig. S1, online supporting information).

Characteristics of included studies
A summary of the included studies is presented in Table SI. The three prospective studies stated measurement time points in advance [14][15][16] and two retrospective studies described the use of a standard protocol which included follow-up time-points. 17,18 Five studies provided information about missing data and loss to follow-up (Table SI). 14,15,[17][18][19] Ten studies included only children and adolescents with CP aged up to 24 years. [14][15][16][17][19][20][21][22][23][24] From the two studies including patients older than 20 years of age, 18,25 the percentage patients to include (>75% of the participants were aged up to 20y) could be derived from the reported mean and range. Four studies included participants with unilateral CP, 14,17,19,21 of which three involved those described as having spastic CP. 17,19,21 Indications were based on presentation of pronation deformity, deficient active wrist extension with adequate digital control, wrist flexion deformity with the flexor carpi ulnaris as the primary deforming force, and adduction of the thumb ray with flexion at the thumb.

Risk of bias within studies
There was an overall high risk of bias within the included studies (Table I). In all retrospective studies the risk of bias  20 C C S C S S S C Donadio et al. 22 C C S C S S S C House et al. 23 C C S C S S M C Libberecht et al. 18 C C S C S M M C Louwers et al. 15 S M S S L M M S Matsou et al. 24 C C S C S S S C Matsou et al. 25 C C S C S S S C Ponten et al. 16 C S S S L S M C Roth et al. 21 C C S C S S S C Smitherman et al. 17  was critical for the items on selection (owing to lack of allocation concealment, loss to follow-up), confounding (inherently to non-controllable studies, different baseline characteristics), and measurement of outcomes (blinding of outcome assessment). Three studies 14,15,17 were judged to be at serious risk of bias in at least one domain, but not at critical risk of bias in any domain.

GRADE assessment of the quality of evidence
The quality of evidence was very low for each postoperative activity-based outcome after UES in children and adolescents with CP (Table II). The scarcity of comparative studies, the selection of participants, and the lack of blinding in outcome assessment introduced a high risk of bias, which was accounted for in the GRADE analysis.  18,[20][21][22][23][24][25] ranging from 0 (no use of the hand) to 8 (complete spontaneous use of the hand). The mean House Functional Classification score changed significantly in the studies, suggesting that the affected arm/hand changed from a (fair) passive assist before surgery to a (fair) active assist after surgery. 23 Scoring of the JHFT and the BBT is based on the time it takes the patient to perform the unimanual tasks. No change after UES was found in the speed of performing a unimanual task performed with the affected hand. For interpretation of change, knowledge about the minimal clinically important difference is important. Unfortunately, these differences are not known for the JHFT, BBT, and House Functional Classification.

DISCUSSION
This systematic review has shown that there is very low quality of evidence for the effects of UES on activities and participation of children and adolescents with CP. The methodological quality of the 12 included studies was poor and evidence for comparative effects is limited. Previous reviews have demonstrated positive effects of UES in children and adolescents with CP on upper limb function (i.e. dexterity, range of motion at the wrist and forearm, and grip strength). [38][39][40] Our review evaluated the effect on patients' functional and perceived performance measured with validated activity-based outcome measurements rated by clinicians or patients/caregivers. Patients' functional performances were measured in five studies [14][15][16][17]19 on quantifiable tasks with the SHUEE, AHA, JHFT, or BBT and in seven studies 17,18,21-25 by a classification.
After UES, improvements were reported in patients' functional performance (what the patient usually does) (SHUEE, AHA, and ABILHAND) and on patients' selfperception of the ability to use the affected arm (COPM). No improvements were noted for speed of hand skills or what a patient is able to do on request (capacity) (JHFT and BBT). However, interpreting these findings is limited in view of the methodological limitations of the studies.  15 Significant 31 b Jebsen-Taylor Hand Function Test 27 Van Heest et al. 19 Not significant Unknown c House Functional Classification 23 Carlson et al. 20 Significant Unknown c Libberecht et al. 18 Significant Unknown c Roth et al. 21 Significant Unknown c Donadio et al. 22 Significant Unknown c House et al. 23 Significant Unknown c Matsou et al. 24 Significant Unknown c Matsuo et al. 25 Significant Unknown c Measuring performance Assisting Hand Assessment [28][29][30][31] Ponten et al. 16 Significant 56 d Van Heest et al. 14 Significant Unknown a,d Louwers et al. 15 Significant 71 d SHUEE SFA 32 Van Heest et al. 19 Significant Unknown c Smitherman et al. 17 Significant Unknown c Van Heest et al. 14 Significant Outcome measures Study Improvement MCID (% of participants) COPM-P 15 Louwers et al. 15 Significant 80 e ABILHAND(-kids) 15 Louwers et al. 15 Significant 55 f Visual Analogue Scale 15 Louwers et al. 15 Significant 62 g SHUEE SFA, Shriners Hospital Upper Extremity Evaluation spontaneous functional analysis; COPM-P, Canadian Occupational Performance Measure performance scale. a Minimal clinically important differences (MCIDs) are unknown, because no individual data are given in the paper. b The percentage with a true change (with 95% certainty) of at least six blocks per minute (measured by the same rater before and after the intervention). c MCIDs are unknown for this outcome measure. d The percentage with at least the smallest detectable change of five Assisting Hand Assessment units (with 95% certainty), which reflects a true change (not measurement error alone) with a standard deviation of 1.96. e The percentage with at least a 2-point change, which is considered to be a clinically meaningful difference between groups of patients. f The percentage with at least the smallest detectable change of 1.18 logits (with 95% certainty), which reflects a true change (not measurement error alone) with a standard deviation of 1.96. g The percentage with at least the minimal clinically important difference of 1.37cm.

Review 25
Implications for practice and research Considering the overall very low quality of the evidence, it is not possible to make clinical recommendations on the effect of UES. However, the positive results of the effect of UES on activities and participation presented in all included studies certainly justify future controlled studies.
A core set of validated outcome measures Different validated activity-based outcome measures were used in the included studies, which showed that clinicians and patient/caregivers were positive about the effect on activities and participation after UES. To enhance the comparability of studies and to perform pooled analysis, the use of a core set of validated outcome measures to gather and share data in international databases is recommended. This information will be important to improve selection criteria, to indicate specific surgical procedures, and to predict outcomes for UES. On the basis of the findings of this review, we suggest adding at least the three activity-based outcome measures to the core set when evaluating the effect of UES on activity and participation: the AHA, SHUEE, and COPM. The SHUEE and AHA should be included because they evaluate the use of both hands together; the SHUEE has more components of measuring capacity and the AHA of measuring performance. The COPM can be used to measure patient-related outcomes of perceived performance and satisfaction of the ability to perform the activity.
Apart from these activity-based outcome measures, more assessments at all levels of the International Classification of Functioning, Disability and Health ('body function and structure', 'activity and participation') are needed to recognize the impact of the changes after UES on patients' functioning and the possibilities for engaging fully in their lives.

Effect of postoperative therapies after UES
To be able to interpret the effect of UES it is necessary to have consensus about postoperative therapy, because the use of different therapies is likely to influence the outcomes after UES on activites and participation. Future studies should compare postoperative therapies to identify the optimal frequency, duration, intensity, and focus (to improve function and/or activities and participation). A period of postoperative immobilization in plaster will always follow UES. However, there is a lack of knowledge about the effect of immobilization in plaster on the results after UES. More knowledge is also needed about aspects such as the optimal position of the arm/hand (e.g. the degree of any over-correction) and the duration of casting.

Long-term outcomes after UES
Future studies should also evaluate long-term outcomes. It is not well known whether UES interventions continue to add benefit over years or whether the gains are lost with ageing. More high-quality comparative effect studies with a large number of participants are needed to determine optimal patient selection criteria and the indications for specific UES procedures.

Limitations
The findings of this systematic review should be interpreted in the context of its limitations. Furthermore, the retrospective case-series design used in most studies means the evidence is initially rated low, and has a high risk of bias, such as recall and publication bias which may have limited the available evidence.
Many studies were excluded because they used unique, individualized, and often qualitative activity-based outcome measures. For example, daily activities were evaluated as a qualitative measure of function, or a questionnaire was used in which participants were asked about the change in hand use after UES. A lack of reported statistical precision (e.g. no estimates of effects with confidence intervals) was found within the included studies, making pooled analyses impossible.

CONCLUSIONS
This systematic review has shown that there is very low quality of evidence for the effects of UES on activities and participation of children and adolescents with CP. In all 12 included studies, the ability and perception of the patient to use the hand(s) and perform activities improved significantly after UES. However, studies had poor methodological quality and reported very low quality of evidence for the effects of UES on activities and participation of children and adolescents with CP. More high-quality multidisciplinary studies are needed to obtain better insight into the comparative effects of UES on activities and participation in this group.

SUPPORTING INFORMATION
The following additional material may be found online: Appendix S1: Search strategy. Table SI: Summary of included studies Figure S1: Flow diagram of studies identified for inclusion in the review.