Repeat upper limb botulinum toxin A injections: a reflection of clinical practice

Management of upper limb spasticity in children with congenital hemiplegia has gained increased attention in the last decade owing to the impact of this type of spasticity on day-to-day functional activities and burden of care. Intramuscular injections of botulinum toxin A (BoNT-A) to the upper limb forms part of the treatment repertoire adjunctive to upper limb training in the management of spasticity. Single dose injections to the upper limb have been reported in a number of randomized controlled trials. Results of a recent systematic review and meta-analysis indicated a small treatment effect favouring BoNT-A and upper limb training compared with upper limb training alone to improve unimanual capacity, and a moderate to strong treatment effect in the achievement of individualized outcomes for children with cerebral palsy.1 However, single dose BoNT-A and upper limb training does not accurately reflect current clinical practice as many children receive repeat injections over time. The study by Olesch et al.2 reports the first randomized controlled trial evaluating three successive cycles of BoNT-A injections and occupational therapy for a young group of children with congenital hemiplegia. Similar to the findings of other single dose studies, BoNT-A injections to the upper limb provided a supplementary effect to occupational therapy for the achievement of individualized goals. Whilst spasticity was progressively reduced over the intervention cycles, this did not translate into gains in unimanual capacity. In contrast, a non-randomized trial of three cycles compared with two cycles of repeat BoNT-A injections to the upper limb for children with hemiplegia yielded a significant treatment effect for unimanual capacity in addition to the achievement of individualized goals.3 The variable impact of BoNT-A and upper limb training to improve unimanual capacity of the impaired limb warrants further scrutiny. First, in many of the single dose trials and in the current study by Olesch et al, the control group received the same amount of upper limb training to the BoNT-A group. The small treatment effect, therefore, reflects the ‘add-on’ effect of BoNT-A already achieved from children receiving upper limb training. Second, a distributed model of upper limb training across single dose BoNT-A studies has been reported with varied duration (4wk–6mo) and frequency (fortnightly to 3 times/wk) with large total dose variance (4h–12h). It is unknown whether a more intensive short duration intervention paradigm (e.g. constraint induced movement therapy or hand arm bimanual intensive training in conjunction with BoNT-A will yield greater treatment effects compared with these distributed models of upper limb training. Third, the variable impact on unimanual abilities may be attributed to lack of sensitivity in the outcome measures used.4 Finally, preliminary evidence is emerging that the type of cortical lesion and cortical re-organization may have an impact on treatment response.5 Further analysis of the characteristics of children who have a greater response to intervention is required. The moderate to strong treatment effect (Canadian Occupational Performance Measure and Goal Attainment Scaling respectively) favouring BoNT-A and upper limb training to achieve individualized outcomes is important.1 It could be argued that individualized outcome measures present problems of reporting bias; however, intervention focused on important functional goals identified by children and their caregivers reflects current clinical practice. Adverse events in response to BoNT-A for upper limb spasticity have been reported in both single and repeat dose studies, which were however, mild, short acting, and reversible.1 Limitations of the study by Olesch et al. and previous upper limb BoNT-A studies are the small sample size and brevity of follow-up. The meta-analysis addresses some of the issues around sample size; however, longer-term follow-up of efficacy and the long-term impact on muscle development are needed. Questions remain about the minimum dosage of therapy required to elicit a treatment effect, particularly relating to unimanual capacity and bimanual performance. Further exploration of the type of upper limb training coupled with BoNT-A is required. A greater understanding of all of these factors can only lead to optimizing the investment of time and resources for both service providers and children with congenital hemiplegia.

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