Repeated botulinum-A toxin injections in the treatment of myelodysplastic children and patients with spinal cord injuries with neurogenic bladder dysfunction.

Objectives: To examine the effects of repeated detrusor injections of botulinum-A toxin (BTX) for possible changes in bladder function, muscular structure of the detrusor, increase in BTX tolerance (tachyphylaxis) and side-effects, as BTX is a new treatment alternative for patients with a neurogenic bladder condition that is difficult to treat and refractory to anticholinergic medication.

Patients And Methods: Between 2000 and 2005, 19 patients with myelodysplasia (MDP) and 25 spinal cord-injured (SCI) patients were treated with repeated suburothelial BTX injections (Dysport, Ipsen-Pharma, Ettlingen, Germany) or injections into the intramural detrusor. The follow-up was > or = 3 years (range 3-5, median 4.5).

Results: Detrusor compliance, bladder capacity, and detrusor pressure at maximum filling improved significantly (P < 0.001) compared to baseline after each BTX injection. There was prolonged efficacy of each BTX administration and all repeated injections in the paediatric and adult patients with neurogenic bladder dysfunction over a median follow-up of 4.5 years. There was no evidence for drug tolerance or changes in the morphological appearance of the bladder. Safety was good: no complications were associated with the injection procedure itself. Early in the treatment programme, three patients who received a dose of 1000 units Dysport showed systemic side-effects and generalized muscle weakness. These resolved without intervention and did not recur after reducing the adult dose to 750 units (paediatric dose 20 units/kg, not >400 units), which seems to be the optimum for good efficacy with an adequate safety margin.

Conclusion: BTX injection is a safe and effective treatment for neurogenic detrusor hyperreflexia. Repeat treatments are as effective as the first: there was no indication of a lack of efficacy due to tachyphylaxis, antibody formation, or fibrosis of the detrusor muscle in this sample.