Botulinum Toxin in the Management of Children with Cerebral Palsy

Abstract

During the past 25 years, botulinum toxin type A (BoNT-A) has become the most widely used medical intervention in children with cerebral palsy. In this review we consider the gaps in our knowledge in the use of BoNT-A and reasons why muscle morphology and function in children with cerebral palsy are impaired. We review limitations in our knowledge regarding the mechanisms underlying the development of contractures and the difficulty in preventing them. It is clear from this review that injection of BoNT-A in the large muscles of both the upper and lower limbs of children with cerebral palsy will result in a predictable decrease in muscle activity, which is usually reported as a reduction in spasticity, for between 3 and 6 months. These changes are noted by the use of clinical tools such as the Modified Ashworth Scale and the Modified Tardieu Scale. Decreased muscle over-activity usually results in improved range of motion in distal joints. Injection of the gastrocnemius muscle for toe-walking in a child with hemiplegia or diplegia usually has the effect of increasing the passive range of dorsiflexion at the ankle. In our review, we found that this may result in a measurable improvement in gait by the use of observational gait scales or gait analysis, in some children. However, improvements in gait function are not always achieved and are small in magnitude and short lived. We found that some of the differences in outcomes in clinical trials may relate to the use of adjunctive interventions such as serial casting, orthoses, night splints and intensive therapy. We note that the majority of clinical trials of the use of BoNT-A in children with cerebral palsy have focussed on a single injection cycle and this is insufficient to understand the balance between benefit and harm. Most outcomes were reported in terms of changes in muscle tone and there were fewer studies with robust methodology that reported improvements in function. Changes in the domains of activities and participation have rarely been reported in studies to date. There were no clinical reviews to date that consider the findings of studies in human volunteers and in experimental animals and their relevance to clinical protocols. In this review we found that studies in human volunteers and in experimental animals show muscle atrophy after an injection of BoNT-A for at least 12 months. Muscle atrophy was accompanied by loss of contractile elements in muscle and replacement with fat and connective tissue. It is not currently known if these changes, mediated at a molecular level, are reversible. We conclude that there is a need to revise clinical protocols by using BoNT-A more thoughtfully, less frequently and with greatly enhanced monitoring of the effects on injected muscle for both short-term and long-term benefits and harms.

Joint and Muscle Assessments of the Separate Effects of Botulinum NeuroToxin-A and Lower-Leg Casting in Children With Cerebral Palsy

“…Therefore, we found little evidence that the reduction in hyperactive stretch reflex of the MG post BoNT-A induced muscle remodeling. It is known that the muscle needs more time than the current shortterm (two weeks) follow-up to adapt and no conclusions can be drawn about the medium-and long-term effect of BoNT-A on muscle length (43). Furthermore, muscle remodeling might take place after combining with casting.…”

Botulinum Toxin Injection in Children with Hemiplegic Cerebral Palsy: Correction of Growth through Comparison of Treated and Unaffected Limbs

“…Muscle force-generating capacity is influenced by muscle cross-sectional area [3,4,10,11,17]. Muscle cross-sectional area is highly correlated with muscle thickness, and muscle thickness measured using ultrasonography can be used as a surrogate marker of change in muscle strength [3].…”

“…Recently, Multani et al reported that human volunteers and experimental animals showed muscle atrophy after injections of BoNT-A for at least 12 months [17]. It is unclear whether these changes, mediated at the molecular level, are reversible; muscle atrophy was accompanied with the loss of muscle contraction and replacement by fat and connective tissue [17].…”

“…Recently, Multani et al reported that human volunteers and experimental animals showed muscle atrophy after injections of BoNT-A for at least 12 months [17]. It is unclear whether these changes, mediated at the molecular level, are reversible; muscle atrophy was accompanied with the loss of muscle contraction and replacement by fat and connective tissue [17]. Multani et al concluded that clinical protocols for using BoNT-A must be revised so that it is used more carefully and less frequently and the effects of muscle injection must be monitored more carefully for short-and long-term benefits and harm [17].…”

“…It is unclear whether these changes, mediated at the molecular level, are reversible; muscle atrophy was accompanied with the loss of muscle contraction and replacement by fat and connective tissue [17]. Multani et al concluded that clinical protocols for using BoNT-A must be revised so that it is used more carefully and less frequently and the effects of muscle injection must be monitored more carefully for short-and long-term benefits and harm [17]. As the number of BoNT-A injections increase in spastic CP, the percentage of type 2 fibers in muscles increases and the percentage of type 1 fibers decreases [8].…”