31 Repeated onabotulinum neurotoxin A injections for drooling in children with neurodisability 1 DISCUSSION This study evaluated the effect of repeated onabotulinum neurotoxin A injections in children with drooling. Although there was continued improvement after repeated injections in the vast majority of children, this study also revealed a significant (but slight) objective (drooling quotient) and subjective (VAS) decrease in effect when comparing the first injection to the second and third injection. Moreover, treatment success rates seemed to decline between the first and second, but not between the second and third injection. Each injection showed similar adverse events and no serious adverse events, supporting the safe use of onabotulinum neurotoxin A, also after repeated injections. There are several explanations for the decrease in effect after repeated injections. The second and third baselines for both VAS and drooling quotient were lower than the first baseline. This could be due to an ongoing treatment effect at the baseline measurement of the subsequent injection, gland atrophy, or children who mature and outgrow drooling. However, baselines before each injection have been corrected for in the analysis. Moreover, although one could expect a lower 8-week outcome after the second injection due to: (1) a lower baseline, (2) survivor bias, or (3) presumably gland atrophy, both 8-week drooling quotient and VAS were slightly higher at the second injection compared to the first injection. Therefore, the decrease in effect cannot be neglected. Another explanation for the decrease in effect could be parotid compensational hypersalivation. One study mentioned dilated ducts and more mucus accumulation in parotid glands after resection of the submandibular glands in rabbits.20 Another study revealed increased parotid salivary flow rate after botulinum neurotoxin A injections in the submandibular glands, which indicated parotid gland compensation.13 Correspondingly, most children in our study received onabotulinum neurotoxin A injections in the submandibular glands only, leaving the parotid glands untreated, which could have led to compensational hypersalivation of the alternative glands. This would, however, have resulted in higher subsequent
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