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Review Article

Efficacy of Upper Limb Therapies for Unilateral Cerebral Palsy: A Meta-analysis

Leanne Sakzewski, Jenny Ziviani and Roslyn N. Boyd
Pediatrics January 2014, 133 (1) e175-e204; DOI: https://doi.org/10.1542/peds.2013-0675
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Abstract

BACKGROUND AND OBJECTIVE: Children with unilateral cerebral palsy present with impaired upper limb (UL) function affecting independence, participation, and quality of life and require effective rehabilitation. This study aims to systematically review the efficacy of nonsurgical upper limb therapies for children with unilateral cerebral palsy.

METHODS: Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Embase, the Cochrane Central Register of Controlled Trials, and PubMed were searched to December 2012. Randomized controlled or comparison trials were included.

RESULTS: Forty-two studies evaluating 113 UL therapy approaches (N = 1454 subjects) met the inclusion criteria. Moderate to strong effects favoring intramuscular injections of botulinum toxin A and occupational therapy (OT) to improve UL and individualized outcomes compared with OT alone were identified. Constraint-induced movement therapy achieved modest to strong treatment effects on improving movement quality and efficiency of the impaired UL compared with usual care. There were weak treatment effects for most outcomes when constraint therapy was compared with an equal dose (amount) of bimanual OT; both yielded similar improved outcomes. Newer interventions such as action observation training and mirror therapy should be viewed as experimental.

CONCLUSIONS: There is modest evidence that intensive activity-based, goal-directed interventions (eg, constraint-induced movement therapy, bimanual training) are more effective than standard care in improving UL and individualized outcomes. There is little evidence to support block therapy alone as the dose of intervention is unlikely to be sufficient to lead to sustained changes in UL outcomes. There is strong evidence that goal-directed OT home programs are effective and could supplement hands-on direct therapy to achieve increased dose of intervention.

  • Abbreviations:
    AHA —
    Assisting Hand Assessment
    BoNT-A —
    botulinum toxin A
    CI —
    confidence interval
    cCIMT —
    classic constraint-induced movement therapy
    CIMT —
    constraint-induced movement therapy
    COPM —
    Canadian Occupational Performance Measure
    CP —
    cerebral palsy
    ES —
    effect size
    HABIT —
    hand arm bimanual intensive training
    mCIMT —
    modified constraint-induced movement therapy
    NDT —
    neurodevelopmental treatment
    OT —
    occupational therapy
    PEDro —
    Physiotherapy Evidence Database
    PMAL —
    Pediatric Motor Activity Log
    QUEST —
    Quality of Upper Extremity Skills Test
    RCT —
    randomized controlled trial
    SMD —
    standardized mean difference
    UL —
    upper limb

    • Congenital hemiplegia, the most common form of cerebral palsy (CP), accounts for 1 in 1300 live births.1 For children with unilateral CP, the effect on upper limb (UL) function is often more pronounced than that on lower limb function,2 with resultant limitations in daily independence, participation, and quality of life. Rehabilitation addressing UL dysfunction is paramount to promote better use of the impaired arm and hand in day-to-day bimanual activities and to achieve functional independence in home, school, and community endeavors.

    A number of UL rehabilitation approaches have been reported in children with unilateral CP. Our previous systematic review and meta-analysis identified 12 randomized controlled trials (RCTs) of constraint-induced movement therapy (CIMT), hand arm intensive bimanual training (HABIT), neurodevelopmental treatment (NDT), and intramuscular injections of botulinum toxin A (BoNT-A) augmenting occupational therapy (OT).3 Findings suggested that intramuscular injections of BoNT-A provided a modest supplementary effect to OT on improving UL outcomes and a strong effect on improving individualized goals. The limited studies of NDT indicated weak to moderate effects on improving quality of UL movement and fine motor skills, despite being commonly used in clinical practice.4,5 The small number of trials of CIMT and HABIT at the time, and lack of uniform outcome measures, limited pooling of data across trials. Individually, there appeared to be promising results suggesting that these 2 high-intensity therapies might yield significant gains in UL function. Adequately powered RCTs of CIMT and HABIT using reliable and valid outcome measures were recommended.3

    In the past 4 years, a large number of RCTs particularly investigating CIMT and modified CIMT (mCIMT) have emerged. Classic CIMT (cCIMT), described in earlier studies, involved placing a full arm cast on the unimpaired UL for 21 consecutive days, accompanied by intensive training for 6 hours each day.6 Modifications to the classic protocol (mCIMT) have been made to make it more child-friendly.7 mCIMT protocols similarly involve restraint of the unimpaired UL, with variations in the type of restraint applied (eg, glove, mitt, sling), and are accompanied by repetitive unimanual task practice. mCIMT departs from cCIMT in terms of the model of therapy delivery (intensive short duration, longer duration distributed model) and dose of intervention. Recently, hybrid models sequentially applying mCIMT followed by bimanual training have been reported.8,9 As a result of the increase in RCTs of UL therapies, conclusions of our previous systematic review need updating. The aim of this systematic review was to determine the efficacy of all nonsurgical UL therapies for children and youth (aged 0–18 years) with unilateral CP on UL outcomes, achievement of individualized goals, and self-care skills.

    Methods

    Search Strategy

    Five databases were searched from inception to December 2012 (Medline, CINAHL [Cumulative Index to Nursing and Allied Health Literature], Embase, PubMed, and the Cochrane Central Register of Controlled Trials). Exploded Medical Subject Heading (MeSH) terms and key words used were as follows: (1) cerebral palsy OR hemipleg*, AND (2) child OR infant OR adolescent, AND (3) physical therapy/physiotherapy OR occupational therapy OR neurodevelopmental therapy/bobath OR functional therapy OR motor learning OR splints OR casts, surgical or botulinum toxin A/neurotoxin OR functional electrical stimulation/neuromuscular electrical stimulation OR resistance training/strength* OR conductive education OR virtual reality OR constraint induced movement therapy OR bimanual training OR action observation OR mirror therapy, AND (4) UL OR upper extremity OR arm OR hand, AND (5) randomized controlled trial/randomized trial OR random sampling OR double-blind method OR single blind method OR placebo. Additional hand searching of reference lists was performed. A language restriction to publications in English was included due to lack of translation services.

    Inclusion Criteria

    Eligibility for inclusion, based on title and abstract, was assessed independently by 2 reviewers (L.S. and R.N.B.). Abstracts meeting inclusion criteria or requiring more information from the full text to clarify inclusion were retained. Articles were included when 100% agreement between reviewers was achieved. Inclusion criteria were as follows: (1) study was an RCT, (2) population comprised children 0 to 18 years of age with unilateral CP, (3) study evaluated the efficacy of a nonsurgical UL therapy or adjunctive treatment in combination with UL therapy, (4) outcomes measured UL unimanual or bimanual capacity and performance, achievement of individualized goals, or self-care skills. Articles were excluded if they used quasi-randomization methods, did not include a subset of children with unilateral CP, provided general developmental therapy without specified UL training, or outcomes assessed impairment, quality of life, or participation.

    Data Extraction, Quality Assessment, and Analyses

    Structured data extraction forms were developed. For studies that did not have the required data published, authors were contacted to request relevant information. Study methodology, number of participants, and intervention and control group details were summarized (Table 1). The methodologic quality of included studies was rated independently by 2 reviewers (L.S. and R.F.) by using the Physiotherapy Evidence Database (PEDro) scale.10 Ten criteria were each scored as either 0 or 1, with a possible total score of 10. Disagreements were resolved by a third reviewer (J.Z.).

    View this table:
    TABLE 1

    Study Characteristics and Methods of RCTs of Nonsurgical Interventions in Children With Congenital Hemiplegia

    Data management and analyses were performed by using RevMan 5.1 (Cochrane Collaboration, Oxford, England). Continuous outcomes for each study were summarized by using means, effect sizes (ESs), and 95% confidence intervals (CIs). An ES of 0.2 was considered small, 0.4 to 0.6 moderate, and 0.8 large. For meta-analyses, standardized mean differences (SMDs) and 95% CIs were calculated. Pooled treatment effects were calculated across trials by using a fixed-effects model when trials used similar interventions and outcomes on similar populations. When substantial heterogeneity between studies was evident from the I2 statistic, a random-effects model was used.11 Data partly or in whole duplicated in a number of publications were scrutinized, and only the most complete data set was included. Outcomes with inadequate reported validity and/or reliability were excluded from meta-analysis.

    Results

    Description of Studies

    A total of 302 unique references were identified, and 55 full-text articles retrieved for full appraisal. Forty-nine publications reporting 42 trials were included (Fig 1). Study characteristics and methods of included RCTs are summarized in Table 1.

    FIGURE 1
    FIGURE 1

    Results of search strategy of UL systematic review. QOL, quality of life.

    Thirteen types of UL interventions and numbers of participants were identified: NDT (2 studies; n = 122),12,13 intramuscular injections of BoNT-A and OT (11 studies; n = 322),14–24 cCIMT (3 studies; n = 56),6,25–28 mCIMT (15 studies; n = 578),7,29–47 hybrid model (mCIMT and bimanual training; 2 studies; n = 68),8,9 forced-use therapy (2 studies; n = 54),48,49 HABIT (1 study; n = 20),50 OT home programs (1 study; n = 35),51 UL lycra splints (1 study; n = 16),52 context-focused therapy (1 study; n = 128),53 mirror box therapy (1 study; n = 10),54 acupuncture combined with OT (1 study; n = 75),55 and action observation training (1 study; n = 15).56 A number of studies reported different domains of outcome (eg, activity, participation)25,33,36 or different times for follow-up34,39,43 in separate papers. Details of each intervention and duration, frequency, and intensity of intervention for control and comparison groups are summarized in Table 2.

    View this table:
    TABLE 2

    Structure and Content of Nonsurgical UL Intervention Programs for Children With Congenital Hemiplegia

    Age of participants across trials ranged from 7 months to 16 years; the majority were preschool- to school-aged children. One study reported outcomes for infants <1 year of age,6 and 10 studies reported on children <2 years of age.12,13,20,29,30,37,40,47,53,55 Most studies targeted children with unilateral CP, and 13 included children with other subtypes of CP (eg, quadriplegia).

    Overall dose, frequency, intensity, and duration of therapy varied across studies. OT after UL injections of BoNT-A ranged from 1 session per fortnight14 to 3 times per week15,24 for a minimum of 4 weeks19 to a maximum of 6 months.15,24 Home programs were provided in 4 studies, with minimal detail.16,17,20,22 Total doses of therapy ranged from 4 to 78 hours.15,19,24 Higher intensities and dosage of intervention were reported in studies of cCIMT, mCIMT, HABIT, and hybrid therapy. Short-duration, high-intensity programs ranged from 2 to 3 weeks’ duration providing 6 hours of daily therapy, with totals of 60 to 126 hours.6,26,27,50 Less-intensive, longer-duration models delivered intervention over 4 to 10 weeks, ranging from 1 to 3 sessions per week, 1 to 4 hours per session.8,29–31,37,38,40,42,44–47 These models often relied on caregivers to provide varying amounts of home practice to achieve the required dosage of intervention, with the expected total ranging from 15 to 168 hours.31,37,40,42,44,47 Studies delivered intervention in context at home/preschool,26,31,37,40,43,44 in a clinic,6–8,35,41,50 or in the community.32

    Qualitative Assessment

    Quality ratings of the study design are reported in Table 3. Twelve studies were of very high methodologic quality, scoring ≥8 on the PEDro scale.10 Fourteen studies were of poor methodologic quality, scoring <6 on the PEDro scale (BoNT-A,21–23 cCIMT,6,25,26 mCIMT,7,29,30,38,44 forced-use therapy,48 and other UL interventions50,54,56). Twenty-six studies (57%) did not report concealed allocation. Baseline equivalence between groups was not present in 12 studies (26%). Data from 6 studies (9 publications) were not included in meta-analyses. One study reported median scores,15 6 did not present summary statistics of central tendency and variability,21,22,25,28,38,56 and 2 reported change scores with or without SDs.41,55

    View this table:
    TABLE 3

    Methodologic Quality Assessment of Included Studies of Nonsurgical UL Interventions for Children With Congenital Hemiplegia: PEDro Scale

    For quantitative comparison of outcomes, data were available to pool across trials and 2 main comparisons were performed: (1) BoNT-A and OT versus OT alone and (2) cCIMT or mCIMT versus (a) a control group or therapy group receiving a lesser dosage of therapy or (b) a comparison group receiving an equivalent dosage of an alternative intervention.

    Primary Outcomes: Unimanual and Bimanual UL Function

    Results of studies reporting UL outcomes are summarized in Table 4. All meta-analyses are summarized in Table 5 and depicted in forest plots in Figs 2 and 3. Data from 4 studies of BoNT-A and OT (n = 55) compared with OT alone (n = 53) scored an SMD of 0.35 (95% CI: −0.03 to 0.73; P = .07) for quality of UL movement on the Quality of Upper Extremity Skills Test (QUEST). This difference was not sustained at 6 to 8 months postintervention. QUEST scores on the Grasp Domain were pooled for 3 studies comparing mCIMT (n = 72) with a control group (n = 65) and yielded an SMD of 0.30 (95% CI: −0.04 to 0.64; P = .08). When mCIMT (n = 60) was compared with a group receiving an equal dose of an alternate intervention (n = 54), the effect on the QUEST Grasp Domain was an SMD of 0.11 (95% CI: −0.26 to 0.47; P = .57). Movement efficiency measured on the Bruininks-Oseretsky Test of Motor Proficiency subtest 8 achieved a strong treatment effect favoring mCIMT compared with a control group (SMD: 1.95; 95% CI: −1.01 to 4.95; P = .20) and compared with an equal-dose comparator (SMD: 0.82; 95% CI: 0.12 to 1.52; P = .02). There was a negligible effect of mCIMT compared with an equal dose of bimanual training on bimanual outcomes measured on the Assisting Hand Assessment (AHA) (SMD: −0.04; 95% CI: −0.42 to 0.35; P = .86) and a weak effect when compared with a control group (SMD: 0.13; 95% CI: −0.39 to 0.66; P = .62).

    View this table:
    TABLE 4

    Summary of Results of Studies of Nonsurgical UL Interventions Reporting on UL Outcomes

    View this table:
    TABLE 5

    Summary of Meta-analyses

    FIGURE 2

    Meta-analyses of the effect of BoNT-A and OT versus OT alone. A and B, Results of UL quality of movement postintervention and 6 to 8 months postintervention, respectively: QUEST. C, Results of UL quality of movement 6 months postintervention: Melbourne Assessment. D and E, Results of individualized outcomes postintervention and 6 months postintervention, respectively: COPM performance. F and G, Results of individualized outcomes postintervention and 6 months postintervention, respectively: COPM satisfaction. H and I, Results of individualized outcomes postintervention and 6 to 9 months postintervention, respectively: GAS. J and K, Results of self-care outcomes postintervention and 6 months postintervention, respectively: PEDI Self-Care Functional Skills Scale. GAS, Goal Attainment Scale; IV, inverse variance; PEDI, Pediatric Evaluation of Disability Inventory.

    FIGURE 3

    Meta-analyses of the effect of CIMT or mCIMT versus control (unequal dose) or comparison (equal dose). A and B, Results of grasp postintervention and 6 months postintervention, respectively: QUEST Grasp Domain. C and D, Results of unimanual and bimanual movement efficiency postintervention and 3 to 6 months postintervention, respectively: BOTMP subtest 8. E and F, Results of bimanual performance postintervention and 6 months postintervention, respectively: AHA. G, Results of individualized outcomes postintervention: COPM performance. H, Results of individualized outcomes postintervention: COPM satisfaction. BOTMP, Bruininks-Oseretsky Test of Motor Proficiency; IV, inverse variance.

    Achievement of Individualized Goals

    Results of studies reporting individualized outcomes are summarized in Table 6. Canadian Occupational Performance Measure (COPM) performance scores were pooled from 3 studies comparing BoNT-A and OT (n = 55) with OT alone (n = 53), with an SMD of 0.30 (95% CI: −0.09 to 0.70; P = .14). Goal Attainment Scale scores were pooled from 4 studies that compared BoNT-A and OT (n = 73) with OT alone (n = 71) and received an SMD of 0.92 (95% CI: 0.57 to 1.27; P < .0001). At 6 months postintervention, a moderate effect was sustained (SMD: 0.56; 95% CI: −0.01 to 1.13; P = .06). A small treatment effect favoring bimanual training (n = 39) over an equal dose of mCIMT (n=40) was found with pooled data from 2 studies on the COPM performance and satisfaction scales (SMD [95% CI]: −0.13 [−0.58 to 0.31; P = .55] and −0.24 [−0.68 to 0.20; P = .29], respectively). There was a negligible effect of mCIMT compared with a comparison group (unequal dose) for data pooled from 2 studies for COPM performance (SMD: 0.05; 95% CI: −0.38 to 0.48; P = .83).

    View this table:
    TABLE 6

    Summary of Results of Studies Reporting on Individualized Outcomes

    Self-Care Outcomes

    Results of studies reporting self-care outcomes are summarized in Table 7. Data were pooled from 3 studies of BoNT-A and OT (n = 62) compared with OT alone (n = 60), with an SMD of −0.03 (95% CI: −1.09 to 0.22; P = .94).

    View this table:
    TABLE 7

    Summary of Results of Studies Reporting on Self-Care Outcomes

    Adverse Events and Clinical Feasibility and Acceptability

    Short-acting and reversible adverse events reported after BoNT-A injections included nausea and vomiting18,19,47 and transient weakness.14,19,20,47 Minor skin irritations were reported after casting for cCIMT.6 Poor tolerance with wearing a mitt/constraint in mCIMT was reported in 5 studies (8%–20% of cohort).7,29,31,37,40 Difficulties achieving the proposed dose of home practice/constraint wear were reported in studies of mCIMT,7,30,37,40,47 ranging from achievement of 50%7,30 to 80%35 of the anticipated dose.

    Discussion

    This updated systematic review of nonsurgical UL interventions in children with unilateral CP highlighted an almost fourfold increase in publications since the previous review published in 2009. Forty-two RCTs reporting 14 types of UL rehabilitation with a total of 1454 participants met a priori inclusion criteria.

    The greatest increase in publications has been for contemporary, motor-learning–based approaches (cCIMT, mCIMT, hybrid models, HABIT). Individually, these studies have predominantly reported improved UL outcomes compared with usual care delivered at a substantially lower dosage. Results of meta-analyses revealed modest to large effects of mCIMT on improving efficiency and quality of movement of the impaired UL compared with usual care. Two studies, however, found minimal differences between groups. One compared an average of 114 hours of mCIMT to 47 hours of bimanual OT47; the other compared 72 hours of mCIMT to 44 hours of bimanual OT.37 Together, these results suggest that 40 hours of therapy was adequate to yield meaningful clinical changes in UL and individualized outcomes. One study directly compared 126 with 63 hours of cCIMT in a small group of 3- to 6-year-old children and found that no benefit was conferred by the additional time.27,28 The exact critical threshold dose of intervention required to achieve meaningful changes in UL function remains unknown.

    Individually, studies comparing intensive unimanual therapy (CIMT, mCIMT) or hybrid therapy with standard care of a lesser dose have revealed modest to strong treatment effects across most UL outcomes.6,8,26,45,46 In contrast, trials comparing intensive unimanual therapy (eg, mCIMT) with an equivalent dose of bimanual training have reported weak to modest treatment effects on most outcomes.31,32,35,38 Results of meta-analyses confirmed minimal differences between these approaches, because both yielded similar UL improvements. Findings suggest that meaningful clinical outcomes may be related to dose of therapy rather than the specific treatment approach. Since our previous systematic review, a greater number of studies have reported valid and reliable outcomes, allowing pooling of data for meta-analyses. The Pediatric Motor Activity Log (PMAL) has been used in 8 studies of cCIMT or mCIMT, with strong ESs reported across individual trials. However, we chose to exclude the PMAL from meta-analysis. Significant concerns have been raised about the measure.57 The original version6 lacks sufficient evidence of reliability and validity. Subsequently, a revised version submitted to Rasch analysis was reported58 in addition to a second alternative revision.59 Both revisions were called PMAL-R, causing confusion over the version used in each study. A further validity study of the original PMAL found only fair criterion validity for the how well domain (how well the child uses their impaired UL) but suggested that the measure was markedly sensitive to change.60 Because each version of the PMAL, however, has different items, rating scales, mode of administration, and overall limited psychometric data,58 we chose to exclude these data from meta-analysis. Future studies using the PMAL to evaluate real-world use of the impaired UL should accurately cite the relevant version used.

    Efforts to adapt CIMT to make the approach more clinically feasible have included reliance on home programs to augment direct therapy. Between 50% and 80% of the anticipated dose was achieved across studies relying on home practice. Qualitative data from 1 study indicated that ∼30% of caregivers found implementing home practice of mCIMT either difficult or very difficult.37 In contrast, home practice of bimanual training (HABIT) achieved 85% of the dose, which may suggest that bimanual home practice is easier to implement than mCIMT. Reported difficulties surrounding tolerance with wearing constraint may contribute to adherence to mCIMT home programs. Results of 1 high-quality RCT of OT home programs provided clinicians with guidelines on developing home programs that have been adopted in a number of mCIMT studies.37,47 Five steps in developing home programs have been proposed, including collaborative partnerships between therapist and caregivers, mutually agreed-upon goals, activity selection to achieve goals, supporting caregivers, and evaluating outcomes.51 Results, again, highlight the importance of activity-based, goal-directed therapy as integral in UL rehabilitation for children with unilateral CP.

    Variation across studies of mCIMT, cCIMT, HABIT, and hybrid interventions was present in the following models of therapy: (1) short-duration, highly intensive group- or individual-based treatment versus a distributed longer-duration, less-intensive intervention; and (2) clinic-based versus home/context-based intervention. One study directly compared home- with clinic-based mCIMT in a small group of children with unilateral CP. Findings suggested some additional benefit of home- over clinic-based therapy in continued improvement in UL function to 3 months postintervention.44 Embedding intervention in natural environments (eg, home, preschool/school) has been suggested to lead to meaningful, generalizable improvements in function.51 Home-based mCIMT and bimanual OT were investigated, with promising results.31,37,40,47 It remains unclear whether there are differences in efficacy of intensive versus distributed models of therapy, and between interventions primarily providing direct hands-on therapy by therapists and indirect therapy relying on caregivers delivering intervention via home programs.

    There was a modest supplementary effect of BoNT-A as an adjunct to OT to improve quality of movement of the impaired UL. Results were not replicated on the Melbourne Assessment; however, data were pooled from only 2 studies with small sample sizes. The sensitivity of the Melbourne Assessment to capture change has been questioned, because most UL studies failed to show the extent of change that would be considered clinically meaningful.8,18,32 There remains a large treatment effect of BoNT-A and OT compared with OT alone on achieving individualized outcomes, which was sustained at 6 to 8 months postintervention. Intramuscular injections of BoNT-A to the UL is an approach that targets body structure and function; however, the accompanying OT focuses on activity-based outcomes. OT differed in intensity, frequency, duration, and content across studies; however, many studies reported goal-directed training as a component of intervention.14–20,24 This finding reinforces that activity-based therapy focusing on goals identified as important by children and their caregivers is an integral aspect of UL intervention. Results of this review concur with the findings of a large Cochrane systematic review of UL BoNT-A61 that OT alone is beneficial and BoNT-A provides a supplementary effect to enhance UL and individualized outcomes.

    There remains limited evidence to support the use of NDT in clinical practice. This approach aims to remediate impairments and facilitate more normal movement patterns62 with the assumption of translation into improved activity performance. No further investigations of NDT have been conducted since the previous systematic review; however, a recent trial compared context-focused with child-focused therapy for children with CP.53 Child-focused therapy targeted impairments and included some elements of NDT, such as facilitation of normal movement patterns and postural control using physical handling techniques provided through practice of functional activities.53 When compared with a context-focused intervention, which involved goal-directed, activity-based training, task, and environmental modifications, there were no significant differences between the interventions.

    Adjunctive therapies in combination with direct therapy were reported for splinting and functional electrical stimulation. Splints are generally not used as a stand-alone intervention but as an adjunct to other UL approaches. Two broad aims of splinting include prevention of contractures and deformities and enhancing UL function through better positioning of the arm and hand. A number of BoNT-A studies have included static night splints as a component of UL intervention.15,16,21,22,24 One study evaluated the additional effect of static night splints accompanying BoNT-A and OT and found improved quality of UL movement at 6 months postintervention compared with BoNT-A and OT alone.21 This was a small study with poor methodologic quality, and findings need to be replicated in an adequately powered trial. The use of functional electrical stimulation as part of an integrated UL therapy program including BoNT-A, OT, and night splint was evaluated in a small trial and found a supplementary effect on UL function.22 The sample size of this study was small and methodologic quality poor; therefore, results should be viewed cautiously. Splinting aimed to improve UL function was evaluated in 1 small study of dynamic lycra UL splints worn for 3 months and accompanied by goal-directed training.52 Findings showed improved goal attainment compared with a control group.

    Two new interventions, mirror therapy and action observation training, have been investigated first in adult stroke rehabilitation and then in small pilot trials for children with unilateral CP.54,56 Mirror therapy creates a visual illusion of a functional impaired arm using a mirror reflection of the unimpaired arm. Movements of the unimpaired limb are performed while watching its reflection in a mirror that shows the image of the unimpaired limb superimposed over the impaired limb. Studies of adults poststroke have shown improved UL motor function and reduced pain after mirror therapy.63 Action observation training involves watching a motor action performed by another person, followed by execution of that motor action, and is believed to tap into the mirror neuron system.64 There is some evidence in adults poststroke that action observation training leads to improved UL motor function.65,66 The 2 pilot trials of mirror therapy54 and action observation training56 in children with unilateral CP showed some preliminary benefits on UL function; however, these approaches should continue to be viewed as experimental until further larger trials can be performed.

    A number of potential limitations exist with the current evidence for UL interventions. Generally, studies continue to report small sample sizes. Compared with the previous review, there is improved consistency in outcome measures. The AHA67 (measure of bimanual performance) has been increasingly used in mCIMT, cCIMT, HABIT, and hybrid models, although the impact of BoNT-A and OT on bimanual performance remains unclear. Bimanual performance should be seen as a key outcome of UL intervention, reflecting that most functional tasks in daily life are bimanual in nature. The importance of bimanual performance was confirmed across a range of UL interventions that highlighted that most goals identified by caregivers and children were bimanual self-care, leisure, and productivity related.18,20,33,35,37,51 The AHA is a valid and reliable performance measure for children with unilateral CP,67 has demonstrated sensitivity to change in clinical trials,32,35,40,47 and is a useful clinical tool for program planning.40,47 As a measure of performance, the AHA is more reflective of actual real-world use of the impaired UL as an assisting hand in bimanual tasks as opposed to unimanual capacity measures that target the child’s best effort in a standardized environment. Greater measurement of individualized outcomes has occurred across UL intervention trials, which is important given the heterogeneity of the population, and reflects a greater focus on goal-directed training.

    Research Implications

    Despite the rapid increase in evaluation of UL therapies for children with unilateral CP, a number of key questions remain:

    1. What is the optimum mode and dose of UL training to accompany intramuscular injections of BoNT-A and how does intervention impact bimanual performance?

    2. What are the most effective interventions to improve UL function in infants <1 year of age?

    3. What is the critical threshold dose of intervention and is there a dose-age relationship?

    4. Is there additional benefit of intensive short-duration interventions versus distributed models of care and does the context of therapy delivery (home, school, clinic, community) impact outcomes?

    5. What are the characteristics of children who achieve clinically meaningful outcomes after intervention? Individual studies have attempted to elucidate predictors of a clinically meaningful response in post hoc analyses7,26,47,50,68; however, findings have not been consistent. An individual patient data meta-analysis may allow greater exploration of subgroups and unique child and intervention factors that might lead to clinically meaningful outcomes.

    Conclusions

    This review highlighted a growing body of evidence for a variety of UL interventions in children with unilateral CP. Synthesizing results of these studies provides therapists with some clear clinical guidelines: (1) therapy should be goal-directed, working on the goals identified by children and their caregivers; (2) goals should be measured objectively; (3) contemporary motor learning approaches that use activity-based therapy should be used; (4) the UL outcomes of therapy should be measured objectively by using reliable and valid outcome measures; and (5) intervention should provide an adequate dose of therapy. Although the exact critical threshold dose of therapy remains unclear, it is certainly more than current standard care. The evidence allows flexibility in how intervention is delivered, due to the variations in models of intervention that have been investigated. Therapists augmenting their direct therapy with home programs should be guided by the work of Novak.51

    Acknowledgments

    We thank Ms Rachel Feeney for performing independent quality review of the included studies and thank Iona Novak, Sue Reid, and Ann-Kristin Elvrum for sharing data for this review.

    Footnotes

      • Accepted September 19, 2013.
    • Address correspondence to Leanne Sakzewski, PhD, BOcc Thy, Queensland Cerebral Palsy and Rehabilitation Research Centre, Level 7, Block 6, Royal Brisbane Hospital, Herston Rd, Herston QLD 4029, Australia. E-mail: l.sakzewski1{at}uq.edu.au

    • Dr Sakzewski conceptualized and designed the review protocol, performed the initial database searches, rated the quality of included trials and extracted data and performed all statistical analyses, and drafted the initial manuscript; Dr Ziviani assisted with the quality ratings of included reviews and reviewed and revised the manuscript; Dr Boyd conceptualized and reviewed the protocol and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted.

    • FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article.

    • FUNDING: Dr Sakzewski received support from National Health and Medical Research Council (NHMRC) TRIP Fellowship 1036183; Dr Boyd received support from NHMRC Career Development grant 1037220.

    • POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

    • COMPANION PAPER: A companion to this article can be found on page e215, online at www.pediatrics.org/cgi/doi/10.1542/peds.2013-3411.

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    Pediatrics
    Vol. 133, Issue 1
    1 Jan 2014
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    Efficacy of Upper Limb Therapies for Unilateral Cerebral Palsy: A Meta-analysis
    Leanne Sakzewski, Jenny Ziviani, Roslyn N. Boyd
    Pediatrics Jan 2014, 133 (1) e175-e204; DOI: 10.1542/peds.2013-0675
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