Botulinum Toxin A Era: Little Steps Towards A Better Understanding

Main Category: Urology / Nephrology
Also Included In: Neurology / Neuroscience
Article Date: 15 Nov 2008 - 1:00 PST

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UroToday.com - Despite an absence of regulatory approval, botulinum toxin A (BoNTA) has been used in a large number of neurogenic patients since its first appearance for the treatment of neurogenic detrusor overactivity (NDO) in patients with spinal cord lesions. Giulio Del Popolo from Florence, Italy, in a thoughtful editorial this year, crystallizes the current state of the art of BoNTA and notes the better understanding about its efficacy and how it works, at least in the short-term. It has become a routine treatment option for NDO after first-line anticholinergic therapy has failed.

Extended indications such as idiopathic detrusor overactivity (IDO), benign prostatic hypertrophy, and bladder pain syndrome are in ongoing trials. The effect of fast paralysis due to BoNTA injection is evident in the detrusor and lasts for up to nearly a year in some patients. How it loses efficacy in the detrusor is under investigation. There appears to be a primary effect on the release of acetylcholine and a secondary effect on bladder afferent pathways, by reducing sensory receptors in the suburothelium, and a central desensitization through a decrease in central uptake of substance P. Urgency is most rapidly and consistently affected, suggesting an early effect on bladder afferent pathways.

These two effects (afferent and efferent) of the drug have to be considered with regard to how it is employed. Patients with spinal cord lesions commonly use intermittent catheterization, and this type of bladder emptying is well accepted by this population. It would be far less acceptable for patients with bladder pain syndrome. In bladder pain syndrome, the secondary effect of BoNTA on bladder afferent pathways must be considered and investigated to improve bladder filling parameters and the clinical impact of urgency, preserving bladder voiding parameters and reducing the risk of urinary retention due to an over-effect on bladder efferent pathways. Dosage and injection sites, intradetrusor or submucosal, and trigone or bladder wall still need further investigation.

Popolo points out that few studies in the literature consider the possible development of drug resistance in patients who have undergone multiple intradetrusor injections. The need for additional basic research studies to better understand suburothelial function and to assess various ways of administration and optimal dosages for different pathologic conditions is evident.

Popolo concludes that BoNTA has extraordinary efficacy in patients with spinal cord lesions, even after repeated infections. In terms of idiopathic detrusor overactivity, benign prostatic hyperplasia, and bladder pain syndrome, it can ameliorate symptoms in the short term, but there is much more to be learned before it finds its place in the armamentarium.

Del Popolo G
European Urology, 54:25-27, 2008
Written by UroToday.com Contributing Editor Philip M. Hanno, MD, MPH

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