| | Functional Outcomes of Intramuscular Botulinum Toxin Type A and Occupational Therapy in the Upper Limbs of Children With Cerebral Palsy: A Randomized Controlled TrialPresented in part to the OT Australia 22nd National Conference, April 6–9, 2003, Melbourne, Australia, and the Australasian Academy of Cerebral Palsy and Developmental Medicine, March 19–20, 2004, Melbourne, Australia. Abstract Wallen M, O’Flaherty SJ, Waugh MC. Functional outcomes of intramuscular botulinum toxin type A and occupational therapy in the upper limbs of children with cerebral palsy: a randomized controlled trial. ObjectiveTo investigate the functional outcomes of botulinum toxin type A (BTX-A) injections to the upper limb in combination with occupational therapy (OT) in children with cerebral palsy (CP). DesignRandomized controlled trial with follow-up at 2 weeks, 3 months, and 6 months. SettingSpecialist outpatient physical disabilities clinic within a public pediatric teaching hospital. ParticipantsEighty children with spastic quadriplegic, triplegic, or hemiplegic CP from these clinics were randomly assigned to BTX-A plus OT, BTX-A alone, OT alone, or a no-treatment control group. InterventionsSingle set of BTX-A (Botox) injections and 12 weeks of OT. Main Outcome MeasuresCanadian Occupational Performance Measure (COPM) and Goal Attainment Scale (GAS). ResultsThe combination of BTX-A and OT resulted in accelerated attainment of functional goals measured by the COPM and GAS. There were no differences between groups on the Melbourne Assessment of Unilateral Upper Limb Function, Quality of Upper Extremity Skills Test, Pediatric Evaluation of Disability Inventory, Child Health Questionnaire, or active and passive range of motion. As expected, there was a significant reduction in muscle tone at follow-up 2 weeks after injection, which returned to baseline level by 6 months. ConclusionsOT enhanced individualized functional outcomes following BTX-A injections in the upper limbs of children with CP. INTRAMUSCULAR BOTULINUM toxin type A (BTX-A) injections chemically denervate a muscle affected by spasticity and hypertonicity by inhibiting acetylcholine release from the terminal junction. The denervation temporarily reduces muscle tone and provides an opportunity to effect changes in motor learning and cortical motor organization.1, 2 The principal aim of treatment using BTX-A injections to the upper limb of children with cerebral palsy (CP) is to enhance function by allowing recipients to employ their treated arm in daily activities more efficiently and effectively. Further aims are to decrease hypertonicity and increase range of motion (ROM), thus preventing contracture formation and delaying the need for surgery.3 Two reviews3, 4 of the existing literature on upper-limb BTX-A injections in children with CP concluded that there was sufficient evidence that these injections reduced hypertonicity and had the potential to improve functional outcomes. Both reviews raised 2 important research issues. The first was whether provision of therapy during the postinjection period could enhance the outcomes of BTX-A injections. The second research issue was whether the reduced hypertonicity caused by BTX-A injections changes children’s ability to use their arm in daily activity; that is, it cannot be assumed that a reduction in hypertonicity is associated with a change in the functional abilities of the upper limb.5 Functional changes are more difficult to define and measure than outcomes such as tone and ROM, especially when related to the upper limb. To be meaningful, functional changes should be specific to individuals’ goals for intervention.1, 6 Clinical reasoning and expert opinion7 suggest that providing occupational therapy (OT) following injections complements the effects of BTX-A and enhances outcomes. The rationale for this therapy is that the period of denervation following injections provides an opportunity for the spastic muscles to be stretched and the usual dominating spasticity patterns to be controlled. Concurrently, motor and physical interventions (eg, casting, motor learning techniques) can be used to guide and direct children’s responses to altered muscle states and to assist them to learn new and more functional motor patterns.3, 7 Completing this therapy involves additional time and resources, both for the provider and for the child and family, and this extra commitment must be accompanied by enhanced outcomes. We have found no studies that have examined the influence of therapy as an adjunct to BTX-A injections to the upper limbs, and thus no evidence that this therapy achieves the aim of enhancing functional outcomes.8, 9 Rather, existing studies have evaluated the add-on effects of BTX-A to the standard provision of therapy.10, 11, 12 This is the first known study, therefore, to evaluate the impact of therapy as an adjunct to BTX-A injections on functional outcomes. The World Health Organization’s (WHO) International Classification of Functioning, Disability and Health (ICF)13 gives health care providers a conceptual framework within which to evaluate clients, plan intervention, and measure outcomes.14 The ICF proposes that the health and well-being of people is related to an interaction between their body function and structure, their ability to complete activities, and their ability to fulfill life roles (termed participation). These factors are also considered within the environment in which they live and in relation to personal factors such as motivation and cognition. Ideally, client management and research would incorporate assessment of the various components of the ICF to determine comprehensively the outcomes of intervention and the real impact on the lives of patients and their caregivers. The ultimate goal of intervention should be to increase participation and, particularly, participation in roles and activities that are meaningful to the client. Despite their relationship to participation in daily life, functional outcomes have infrequently been measured in studies of BTX-A in the upper limb in children with spastic CP. Studies to date have measured muscle tone (eg, Modified Ashworth Scale [MAS], Tardieu scale), ROM, and often grip strength as outcomes.10, 12, 15, 16, 17, 18 These are measures at the level of body function and structure and do not indicate how well children use their arms to carry out activities of daily living. Measures of fine motor performance (eg, Jebsen-Taylor Hand Function Test, Bruininks-Oseretsky Test of Motor Proficiency) and quality of upper-limb movement (Quality of Upper Extremity Skills Test [QUEST], Melbourne Assessment) have been included in some studies10, 11, 12, 15, 16, 17, 18 and can provide important information about changes that occur in upper-limb activity. These assessments are inadequate to conclude that meaningful participation in functional day-to-day activities is achieved. They can only be assumed to have an association with the use of the limb in functional activities.5 The Pediatric Evaluation of Disability Inventory (PEDI) has been used to explore the impact of BTX-A on children’s ability to complete self-care activities.10, 11, 12, 16, 17 There is also a need to explore the impact of BTX-A on children’s performance at school and in leisure activities. It is especially necessary to measure change in those activities that the child and family identify as being important to participation in their life roles. Central goals of intervention in CP should focus on ability and participation.6 Lowe et al11 are the only researchers to include measures of this kind. Both the Lowe11 study and this study include the Canadian Occupational Performance Measure (COPM)19 and Goal Attainment Scale (GAS)20 to objectively measure change on individualized functional outcomes that are important to children and their families. This randomized controlled trial (RCT) addressed the important research issues identified by experts and reviewers.3, 4, 7 Those issues are the impact of therapy in the postinjection period and the impact of BTX-A, with or without therapy, on functional outcomes that are meaningful to children and families. The main objectives of this study were to determine (1) if BTX-A is effective in improving individualized functional outcomes, and (2) if BTX-A in conjunction with OT is more effective than BTX-A alone. Methods  Participants We identified participants from the Physical Disabilities Clinic of The Children’s Hospital at Westmead (Sydney, Australia) and by advertising the study through various pediatric therapy networks. A rehabilitation pediatrician (M-CAW) and a research nurse assessed potential participants to determine eligibility and to collect written informed consent from their families. Children were potentially eligible to participate if they (1) were aged 2 to 14 years and (2) had spastic CP affecting 1 or both upper limbs. One “study limb” was selected, in consultation with the family, for each potentially eligible child. This “study limb” needed to meet additional eligibility and exclusion criteria. The eligibility criteria were: (1) MAS score of 2 or 3 (moderate to significant muscle tone) in at least 1 study limb muscle group, (2) goals identified by the family that were related to the study limb (eg, improve function, hygiene, splint tolerance, or limb positioning), and (3) stable spasticity management intervention (eg, therapy, splints, medications) for at least 6 weeks before trial commencement. Exclusion criteria included (1) significant contracture at the elbow, wrist, or fingers that interfered with completing daily activities as determined subjectively with the family, (2) absence of movement, and (3) fluctuating muscle tone of the study limb. Design and Procedure The study was approved by the Ethics Committee of The Children’s Hospital at Westmead, their recommendations adhered to, and the families and caregivers of all participants gave written informed consent to participate in the study and to have the results disseminated. For this RCT, consenting participants contacted a third party, who was independent of the selection and consent process and who randomly allocated the participant into 1 of 4 groups: OT plus BTX-A, BTX-A alone, OT alone, or a no-treatment control group. This process ensured allocation concealment. Participants were randomly allocated in blocks of 16 (4 participants for each of the 4 groups). The participant’s group allocation was drawn from a large envelope containing 16 sealed envelopes. Block allocation allowed research clinics to be organized so that those children receiving injections were seen on the same day, streamlining access to appropriate injection and sedation facilities. We collected data from June 2000 until May 2002. Outcome measures were completed on 4 occasions: at baseline (the same day as injections if received), and at 2 weeks, 3 months, and 6 months following baseline. Experienced pediatric occupational therapists, a rehabilitation pediatrician, and a research nurse collected the data. The quality of upper-limb function measures were scored from a videotape by independent occupational therapists blinded to group membership and timing of follow-up. Other outcomes were not blinded; however, data collectors and families were not given any access to previously collected data. All allocated participants were accounted for at the end of the trial and intention-to-treat analyses completed. Sample Size A sample size of 19 children per group gives an 80% probability of detecting an effect of 2 points on the 10-point COPM scale.19 In our sample size calculations we estimated the standard deviation (SD) of this outcome (2 points) using data from our phase II trial21 and an estimated drop-out rate of 15%. Interventions BTX-A injections See Wallen et al21 for details of muscle selection, injection site identification, injection procedure, and dosing. At baseline, children in the BTX-A plus OT and BTX-A groups received 1 set of injections of Botox to identified muscles, under local anesthesia and nitrous oxide sedation. Doses were 0.5 to 2U of Botox per kilogram of body weight per muscle with a maximum dose of approximately 12U/kg. OT intervention Starting 1 week after baseline assessments, children allocated to a group involving OT received 1 hour a week of therapy for 12 weeks. The selection of 1 hour a week was based on convention as well as the amount of therapy that is generally feasible for families to attend and therapists to provide. Therapy over 12 weeks was selected to take advantage of the period of denervation.1, 3 Therapy was provided by the children’s usual occupational therapist or at The Children’s Hospital at Westmead. Current practice associated with post BTX-A therapy was that children receiving injections at The Children’s Hospital at Westmead were followed up by their usual therapists. These children were, therefore, exposed to a broad range of intervention modalities. This trial aimed to mirror usual clinical practice so to generalize findings to the true clinical situation. The therapy component of the intervention, therefore, was not standardized but determined by the treating clinicians to ensure that intervention was appropriate for participants to meet their individual goals. Intervention techniques included those aimed at improving impairment (eg, stretching, casting, splinting), and enhancing activities (eg, motor training, environmental modification, practice of specific goal activities). We asked families and therapists to maintain pre-existing levels of therapy through the 6-month study period. Some of the control and BTX-A groups, therefore, received varying amounts of therapy. Those allocated to the 2 OT groups received the twelve 1-hour sessions as part of their group allocation as well as their regular therapy for the remainder of the 6-month study period. Primary Outcomes The COPM19 and GAS20, 22 are described elsewhere.21 The COPM has 2 domains—performance and satisfaction with performance—each of which is rated on a 0 to 10 rating scale. The GAS is reported in normalized T scores, whereby a score of 50 means that goals, on average, are achieved. Secondary Outcomes The Melbourne Assessment of Unilateral Upper Limb Function23 and the Australian Authorised Adaptation of the Child Health Questionnaire (CHQ)24 are described elsewhere.21 Quality of Upper Extremity Skills Test The QUEST25, 26 evaluates quality of upper-limb function in 4 domains: dissociated movement, grasp, protective extension, and weight bearing. It is validated for children aged 18 months to 8 years and was used with participants up to 5 years of age in this study. Only the study limb was assessed, so the scoring was modified to accommodate this. As a consequence the range for the total score was minus 12 to 106. The QUEST has excellent interrater and test-retest reliability26 and good construct and criterion validity. Pediatric Evaluation of Disability Inventory We interviewed parents to complete the functional skills and caregiver assistance scales for the self-care domain of the PEDI.27 These scales measure functional capability in areas such as eating, grooming, dressing, bathing, and toileting. The PEDI is norm-referenced for children aged 6 months to 7.5 years, but can be used with older children if their functional capabilities are less than those expected of a 7.5-year-old child. A normative score is thus available for children aged 6 months to 7.5 years (range of scores, 5–90) and a scaled score can be calculated for all children (range of scores, 0–100). The PEDI has good internal consistency, interrater reliability and validity28 and appears sensitive to change in children with CP.29 Tardieu scale We used the Tardieu scale30 to measure the dynamic component of elbow flexor, wrist flexor, and pronator spasticity. In this study, the score was determined by moving a joint as fast as possible through its full ROM and measuring the angle when the muscles first “catch,” that is, when the stretch reflex is elicited. The difference between the “catch” angle (termed R1) and full passive ROM of the joint (R2) reflects the potential ROM available to the child if spasticity could be eliminated. Proportional change was calculated by the formula: (baseline [R2−R1]−postassessment [R2−R1])×100/baseline (R2−R1). Proportional change measures the proportion of the potentially available change that was actually achieved.31 It has been recommended as a means of reporting change in research where the baseline values of a sample are not homogeneous.31 The dynamic component of the Tardieu scale is clearly responsive to the effects of botulinum toxin injections in the upper limbs of children with CP.21 Because the stability of the Tardieu scale has not been established,32 the same rater assessed each child at each follow-up point to optimize the stability of the data collected. Adverse events Each participant’s medical and research records were retrospectively audited, blinded to group membership. Any events were recorded and then categorized according to whether they could be attributed to BTX-A injections or nitrous oxide sedation. Finally, the groups were compared on the frequency of these events. Data Analysis To account for the group differences at baseline on the COPM, we evaluated the mean change from baseline scores for all outcome measures at each follow-up. In the instances of missing data, data were not carried forward due to length of time between follow-up visits. While some of the data were found to be normally distributed, the data were largely non-normal; thus, nonparametric analyses of variance (ANOVA) were completed. For consistency, ease of interpretation and potential to contribute to a meta-analysis, however, summary statistics of mean, SD, and 95% confidence intervals (CIs) are presented throughout. A separate ANOVA was conducted across the 4 comparison groups at each follow-up. Post hoc testing of between-group differences was completed using nonparametric methods where a significant difference on ANOVA existed. We set the overall α level for the ANOVA models for the primary outcomes (COPM, GAS) at .05. For ANOVA of secondary outcomes and for pairwise comparisons of treatment groups, the Bonferroni adjustment was made to the overall α level of .05, so that only P values less than .01 were considered statistically significant. Wrist flexion data for the Tardieu scale and for ROM were excluded from analyses because there was a significant amount of missing data. Results Eighty children were randomized into 4 groups. Eight children withdrew from the study after randomization and prior to baseline data collection. See figure 1 for the trial profile, which tracks participants and drop-outs through the trial. The remaining 72 children received their intended intervention and their data were analyzed in the group to which they were allocated. Some children missed scheduled appointments due to illness, holiday, or family reasons. Data were missing for some outcomes for some participants due to a consistent carer being unable to complete questionnaires (n=1), missing data collection form (n=1), or due to video-recording errors (n=4). Participant Demographics Demographic and clinical characteristics of the participants are presented in table 2. The mean age overall ± SD was 5 years, 11 months, ± 3 years, 2 months (range, 2–14y) and 64% were boys. Ninety-six percent of study limbs were the nondominant arm and 56% were the left arm. The dominant arm was selected as the study arm for 3 children, all of whom had quadriparesis and whose preferred outcome was to improve the ability of the better functioning limb. There were no significant differences between groups at baseline on the primary outcome measure: the COPM satisfaction scale. The BTX-A plus OT group, however, had a significantly lower score on the COPM performance scale than the OT and control groups at baseline (see table 2). There were no significant differences between groups on any of the demographic characteristics (ie, age, sex, study limb, diagnostic group, MAS score, cognitive status, Tardieu angle of first catch or sensation). Dosages The 40 injected participants received injections in 1 (n=2), 2 (n=11), 3 (n=12), 4 (n=14), or 5 (n=1) muscle groups. The maximum dose ranged from 2.0 to 13U/kg (mean, 8.1±2.9U/kg) (table 3). Clinical indications overrode the study protocol in 2 participants, both of whom weighed over 40kg and who received a total dose of 410U (9.8U/kg and 9.1U/kg, respectively). Primary Outcomes Canadian Occupational Performance Measure The BTX-A plus OT group had the largest change from baseline at both 3 and 6 months and was the only group to have a clinically significant change (mean change as well as the entire 95% CI) of at least 2 points at both follow-up assessments (table 4). This change was significantly different from control for both performance (P=.002) and satisfaction (P=.005) scales at 3 months. The percentage of participants in the BTX-A plus OT group whose COPM score increased by 2 points or more appeared higher in the BTX-A plus OT group than the control group. Goal Attainment Scaling Each participant identified between 3 and 5 goals. The largest category of goals was leisure-related and the most frequently cited goals were for a child to be able to push their arm through a sleeve when dressing, and catching a ball (table 5). At 3 months the only group to achieve a mean normalized T score of 50 was the BTX-A plus OT group, indicating that on average these participants’ goals were achieved. There was a significant difference between the BTX-A plus OT group and the control group (table 6). By 3 months, 55% of participants in the BTX-A plus OT group had achieved a normalized T score of 50; this was significantly different from the control group (P=.003). By 6 months all the treatment groups (but not the control group) had achieved a mean T score of 50. There were no statistically significant differences between groups, however, or between the percentages of participants in each group who had achieved a T score of 50 at 6 months (see table 6, fig 2). Secondary Outcomes Melbourne Assessment Forty-four children aged 5 years and over completed the Melbourne Assessment. There was no difference between groups at baseline and no difference in the amount of change between groups at 2 weeks and 3 or 6 months. The BTX-A plus OT group made statistically significant within-group change at 3 months (mean change, 5.2; P=.004), as did the OT group at 6 months (mean change, 3.9; P=.008). The amount of change, however, was smaller than the clinically significant level of 12% or more recommended in the assessment manual.23 Quality of Upper Extremity Skills Test Twenty-eight children under 5 years completed the QUEST. There were no differences between or within groups in the amount of change from baseline to any of the follow-up points for the QUEST total score. Pediatric Evaluation of Disability Inventory Normative scores could be calculated for 47 children aged up to 7.5 years for both the functional skills and caregiver assistance scales. The range of possible scores is 0 to 100. There were no between-group or within-group differences in the amount of change from baseline in either scale. Scaled scores, which do not adjust for development, were calculated for the entire sample of 72 children. Using scaled scores, there were no significant differences between groups for either the functional skills or caregiver assistance scales at 3 or 6 months. Child Health Questionnaire There were no significant differences between groups on any of the scales of the CHQ. Tardieu scale Data were available for elbow flexors and pronators. Overall, the results indicated that the proportional change in the Tardieu scale for the elbow flexors and pronators of both groups treated with BTX-A was significantly greater than the OT and control groups at both 2 weeks and less so at 3 months. There were no differences between groups in the proportional change on the Tardieu scale at 6 months (table 7). Range of motion Data were available for elbow flexors and pronators. There were no between- or within-group differences in change from baseline for passive ROM of elbow extension or supination at any time points. The only between-group differences in change in active ROM from baseline was a significant increase in active supination in the BTX-A plus OT and BTX-A groups when compared with the control group at 6 months (BTX-A plus OT: mean change, 16.5; BTX-A: mean change, 9.3; OT: mean change, 1.5; control: mean change, −19.5; ANOVA, P=.008). Parent questionnaire Parents were asked to rate how their child’s arm compared with baseline (much worse, a bit worse, much the same, a bit better, much better) (fig 3). Parents perceived more improvement in the BTX-A plus OT group at 2 weeks and improvement in all the treatment groups compared with the control group by 6 months. The majority of the BTX-A plus OT and the BTX groups reported they definitely (BTX-A plus OT, 74%; BTX, 67%) or probably (BTX-A plus OT, 21%; BTX, 11%) would have injections again. Only 1 family in each of these groups reported they would probably not or definitely not have injections again and 3 families reported they would “have to think about it.” Adverse events The frequency of adverse events for each group that may have been associated with injections or sedation was as follows: BTX-A plus OT, 5 (nausea and vomiting 3d postinjection, unsettled a few days after injection, vomiting post nitrous oxide, flu symptoms 2wk postinjection, sick and coughing 2–3wk postinjection); and BTX, 4 (fever overnight 2wk postinjection, sore wrist 2wk postinjection, upper respiratory tract infection, sore hand at 2d postinjection). No child or family reported excessive weakness in their upper limb following injections. The OT group who were not given any sedation also had 4 events reported (illness at 1wk, illness at 2wk post baseline, ill at 2wk appointment, sick with rash at 2–4wk post baseline). The control group did not report any adverse events. Discussion This RCT explored the influence of upper-limb BTX-A injections and OT on family-focused functional outcomes in children with CP, specifically to determine whether OT enhanced the outcomes of BTX-A. Our study design also allowed us to determine the effects of BTX-A when compared with standard OT or no intervention. Our primary outcome measures were the COPM and GAS, individualized measures of activity and participation. We know that changes on clinical measures are not always transferred to client benefits.5 The COPM, a parent/child report measure of activities and participation, ensured that participant benefits were explored. Further, using these individualized measures resolved some of the difficulties of finding consistent measurement tools across our clinically representative but heterogenous group of children with CP.6 The BTX-A plus OT group had significantly more functional gains compared with the control group on the COPM and GAS at 3 months. This early gain was maintained at 6 months. Of note is that the control group also made some gains; however, these gains only reached clinical significance at 6 months on the satisfaction scale. Similarly, the control group did not reach a mean normalized T score of 50 on the GAS, indicating that, on average, goals were not achieved. The changes made by the control group may reflect change associated with time and development, the “usual” therapy received by the control group, or may be a consequence of clearly identifying goals to focus on. It is possible that identifying goals and priorities through a process such as the GAS may be therapeutic in itself.6, 33 The data for the COPM and GAS measures indicated no significant differences between the OT and BTX groups. This might appear that the relative advantages and disadvantages of each form of intervention (ie, cost of blocks of therapy, access to injections and/or therapy, invasive nature of injections) could be considered in selecting between them. Because we did not withhold pre-existing therapy arrangements, some of the children in the BTX group received their routine therapy; thus the equivalence of treatment effects for these 2 groups needs to be considered with caution. Families had no difficulty in identifying several functional goals and indicated that the process (collaboratively identifying goals for intervention that were functional in nature) was very positive. This outcome has also been reported by others.33 It has been enlightening to note that the largest category of goals was related to leisure activities. This reinforces the need to consider leisure as an important focus for intervention. The Melbourne Assessment and QUEST, measures of quality of upper-limb function, were included as secondary outcome measures. There were no differences between groups at any time point. There were, however, gains in participation in upper limb functional activities and a reduction in muscle tone. These changes were not reflected in the Melbourne Assessment score, suggesting that it may not be responsive to change in this context in children with CP. Other studies of BTX-A in the upper limb in CP have reported no change on the Melbourne Assessment both in the absence of changes in other upper limb outcomes12 and despite functional and spasticity changes.21 The results for the QUEST contrast with those from the RCT of Fehlings et al10 using BTX-A in the upper limb of children with CP. Fehlings reported change in the QUEST total score at 1 month postinjection whereas in our study there were no differences between groups. Despite the changes on the COPM and the achievement of goals, especially in the BTX-A plus OT group, there were no differences between groups on the PEDI. Speth et al12 also found no change in the self-care component of the PEDI following BTX-A injections. The failure to detect change on this measure reinforces the need to select outcome measures of specific goals of importance to families, and where actual achievement is compared with participants’ expected achievements. Change on those areas targeted by families may have been subsumed into the large number of items of the PEDI, many of which were not targeted as goals for intervention.33 As expected, the Tardieu findings reflected the pharmacologic effects of the BTX-A. That is, in the 2 groups treated by BTX-A, muscle tone decreased significantly during the period of expected chemodenervation. The effects started to taper off by the 3-month assessment. However, the improvements seen on the COPM and GAS were not lost because the muscle tone returned to baseline levels at 6 months, nor did these changes in muscle tone influence scores obtained on the quality of movement tests: the Melbourne Assessment and the QUEST. These results reinforce the notion that the links between body structure and function and change in activities and participation cannot be assumed.5 It may be argued that the self-report nature of the COPM may have facilitated expectation bias in the parent raters. This seems less likely given the coupling of the GAS with the COPM. The GAS involves setting goals that include objective and measurable outcomes. Thus, the possibility of expectation bias for the GAS is low. The lack of change in passive ROM was expected because study selection criteria required absence of contracture. At baseline the mean passive elbow extension ± SD was 175°±9° and mean passive supination was 170.7°±14.8° indicating close to full passive ROM at the outset. The mean active elbow extension at baseline was 153.4°±24°, with little margin for improvement, especially given that the elbow movement required for functional activities is rarely at full extension. The baseline active supination was 81.4°±47.8°, that is, less than the neutral mid-position and with a large degree of variability. The improvement in active supination in the groups treated with BTX-A and especially the BTX-A plus OT group is a promising outcome for enhanced function. We sought parents’ global perceptions of change in upper-limb function. This gives us an “aggregate judgment” that families make in considering the overall intervention experience and its value in relation to any adverse experiences.5 The parents’ perceptions confirmed the general satisfaction with intervention versus control, and the worthwhile nature of BTX-A injections generally. Particularly noteworthy was the parental report that they considered BTX-A injections sufficiently worthwhile to consider repeating them in the future. The adverse events for all groups were blindly categorized as to the likelihood of being related to injections. The 3 treatment groups (but not control group) had a similar rate of adverse events. These included 1 possible reaction to nitrous oxide sedation and 2 cases of soreness at the injection sites. The failure to detect any adverse events in the control group is likely to be due to the low incidence of ongoing contact with the research team, because no ongoing therapy was provided and because events may not specifically have been recorded, given these participants’ lack of exposure to BTX-A injections. In this study, the BTX-A plus OT group made clear and earlier gains in the primary, functional outcomes compared with all other groups. This provides good evidence for justifying occupational therapy as part of postinjection practice. The survey by Lannin et al8 of OT and physiotherapy practice with children with CP post BTX-A injections found that therapists did not complete measurement of functional outcomes following intervention. Nor did they particularly focus on achieving functional outcomes. With evidence that OT enhances the functional outcomes of BTX-A injections, it is incumbent upon therapists to routinely elicit and promote the families’ and child’s goals during post BTX-A intervention. There are several ways in which this study may inform future research. Restriction of the age group to allow use of 1 measure of upper-limb function across the full age range of participants would provide more meaningful information about this important outcome. Full blinding of outcomes assessors is desirable. The sample size was inadequate to undertake subgroup analysis by diagnosis to determine any differences in the responses of children with different types of CP. Most studies to date have evaluated BTX-A in children with hemiplegia. Children with quadriparesis are intrinsically a heterogeneous group. Studies specifically of children with quadriparesis, however, are also required to answer important clinical questions about their management, responsiveness, and the measurement of meaningful outcomes. Valuable information could be provided by examining outcomes of BTX-A injections in relation to the extent of upper-limb involvement determined by a tool such as the Manual Abilities Classification System34 or the Assisting Hand Assessment.35 It would be useful to explore the relationship of sensation, cognitive ability, and severity of motor involvement (among other variables) to functional outcomes, in order to target children most likely to benefit by intervention. Future research may also explore the aspects of therapy that contribute to enhanced outcomes. Specific approaches such as motor learning principles or constraint-induced movement therapy are worthy of evaluation as specific techniques to enhance function of hemiplegic limbs in CP after BTX-A injections. Conclusions The combination of OT and BTX-A injections enhances the self-reported, individualized, functional outcomes of children with CP. Service providers can be confident that resource allocation toward provision of therapy that is goal directed and family focused following injections is worthwhile. Acknowledgments We gratefully acknowledge the invaluable contributions of the following colleagues for data collection, providing therapy to participants, blinded ratings of videotapes and assisting with preparation of the manuscript: Susan Allan, BAppSc(OT), Katrina Beissel, BAppSc(OT), Betina Fratzia, BAppSc(OT), Christine Imms, BAppSc(OT), MSc(RehabSc), Natasha Lannin, PhD, Suzanne Mackay, BAppSc(OT), Lynn McCartney, RN, BHSc(Nursing), Anna McCauley, BAppSc(OT), Fiona Nelson, Grad Dip (Ch&FamHealth), Rachel Rolinson, BAppSc(OT), Fiona Sampson, BAppSc(OT), Adam Scheinberg, FRACP, FAFRM, MD, and Alison Wesley, BAppSc(OT). References 1. 1Jefferson RJ. Botulinum toxin in the management of cerebral palsy. Dev Med Child Neurol. 2004;46:491–499. MEDLINE 2. 2National Institutes of Health Consensus Development. Clinical use of botulinum toxin. Arch Neurol. 1991;48:1294–1298. MEDLINE 3. 3Hoare B, Imms C. Upper-limb injections of botulinum toxin-A in children with cerebral palsy: a critical review of the literature and clinical implications for occupational therapists. Am J Occup Ther. 2004;58:389–397. MEDLINE 4. 4Wasiak J, Hoare B, Wallen M. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy. Cochrane Database Syst Rev. 2004;(4):. 5. 5Jankovic J, Esquenazi A, Fehlings D, Freitag F, Lang AM, Naumann M. Evidence-based review of patient-reported outcomes with botulinum toxin type A. Clin Neuropharmacol. 2004;27:234–244. MEDLINE |
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7. 7Graham HK. Botulinum toxin A in cerebral palsy: functional outcomes. J Pediatr. 2000;137:300–303. Full Text |
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8. 8Lannin N, Clark K, Scheinberg A. New South Wales therapy practices for children with cerebral palsy who have received botulinum toxin-A. Aust Occup Ther J. 2004;51:208–212. 9. 9Lannin N, Scheinberg A, Clark K. AACPDM systematic review of the effectiveness of therapy for children with cerebral palsy after botulinum toxin A injections. Dev Med Child Neurol. 2006;48:533–539. MEDLINE |
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10. 10Fehlings DL, Rang M, Glazier J, Steele C. An evaluation of botulinum-A toxin injections to improve upper extremity function in children with hemiplegic cerebral palsy. J Pediatr. 2000;137:331–337. Abstract | Full Text |
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Supported by The Children’s Hospital Fund of The Children’s Hospital at Westmead and Allergan Australia. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Reprints are not available from the author. PII: S0003-9993(06)01425-0 doi:10.1016/j.apmr.2006.10.017 © 2007 American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved. | |
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