32 CHAPTER 1 baseline outcomes which it did not. Alternatively, NAb against botulinum neurotoxin A have been suggested to play a role in secondary treatment failure, mostly injected in muscles to decrease spasticity.10–12 One case report described secondary non-response of botulinum neurotoxin B injections in drooling after three successful injections. NAb against neurobotulinum toxin B were identified and additional onabotulinum neurotoxin A injection did not show treatment response either.21 Some children included in this study may also have been treated with botulinum neurotoxin A injections in their limbs because of spasticity which may have induced NAb before the first intraglandular onabotulinum neurotoxin A injection. In a recent cross-sectional study, the prevalence of NAb against onabotulinum neurotoxin A in children treated for spasticity was found to be 15.2%. Also, the study found the most influencing factor to be the single dose per session.9 As this study was done retrospectively, data on whether children were treated with botulinum neurotoxin injection for other indications could not be assessed thoroughly. Although this study certainly revealed a significant reduction in effect between the second and first injection, there was no ongoing decrease in reduction after the second injection while NAb development during onabotulinum neurotoxin A treatment most likely increases with treatment duration.9 Yet, the study was subject to survivor bias, so children with loss of treatment effect after the second injection will presumably not undergo a third injection, indicating that only responders are included for subsequent injections. In summary, there was presumably an ongoing effect of onabotulinum neurotoxin A on drooling which resulted in a lower second and third baseline outcome. Though there was no ongoing decrease in objective effect after the third injection, the decrease in effect compared to the first injections is not neglectable. Future research should evaluate whether NAb play a role in the decrease in effect after repeated botulinum neurotoxin injections in a prospective setting. Despite the decrease in effect after repeated injections, onabotulinum neurotoxin A still
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