Lack of response to botulinum toxin A in patients with hypertrophic pyloric stenosis

Received: 8 September 1998 /Accepted in revised form:16 September 1998Sir: Intramuscular injection of botulinum toxin A is an e•ectivetherapy for children and adults with dystonic and spastic move-ment disorders as well as with achalasia [2, 3, 4]. We report on theuse of botulinum toxin in two infants with hypertrophic pyloricstenosis, neither of whom responded to this treatment. Our resultssuggest that: (1) botulinum toxin A is not a treatment option inhypertrophic pyloric stenosis in infants and (2) the release ofacetylcholine does not play a major role in the pathophysiology ofthis condition.Two unrelated infants (a 3-week-old male and a 5-week-oldfemale) were diagnosed with hypertrophic pyloric stenosis, con-firmed by ultrasound. Following approval by the Ethics committee(Freiburg University) and by the parents who were informed aboutthe experimental nature of this therapy, botulinum toxin A wasdelivered into the pyloric muscle using a flexible, upper gastro-intestinal, endoscopically-guided injection. The dose of botulinumtoxin A was adapted from previous experience in patients withdystonic conditions for the first patient (5 U Dysport/kg bodyweight; total 20 U) and patients with spasticity for the secondpatient (12 U Botox/kg body weight, total 44 U).Neither patient showed either clinical or sonographic responseto treatment during the following 4 days, although this periodshould have been su†cient to achieve a detectable e•ect. Correctadministration application was confirmed by reviewing videorecordings of the procedure. The given dose used for our secondpatient was the same as that used e•ectively for the treatment ofchildren with achalasia [3]. In both of our patients surgicalintervention (Ramstedt procedure) was performed with a successfuloutcome.Acetylcholine is considered to be the primary neurotransmitterwith excitatory e•ects upon smooth muscle [1]. In achalasia the lossor dysfunction of inhibitory neurons which contain vasoactivepolypeptide and nitric oxide results in a predominantly excitatorycholinergic innervation that can be suppressed by botulinum toxinA [4]. In hypertrophic pyloric stenosis the inability to relax thepyloric muscle has been considered to be due to deficiency of nitricoxide synthetase [5]. The lack of e•ect of botulinum toxin Asuggests that the gastric outlet obstruction in hypertrophic pyloricstenosis is not due to a predominantly cholinergic excitatoryinnervation. Instead, hypertrophic pyloric stenosis could be causedby development-related denervation a•ecting both inhibitory andexcitatory pathways.