ABSTRACT
Introduction
Neurogenic detrusor overactivity (NDO) results in involuntary detrusor contractions during bladder filling or storage risking transmission of pressure to the upper urinary tracts and/or significant incontinence. The goals of bladder management in children with NDO prioritize the preservation of renal function, prevention of UTIs, and optimizing quality of life. First-line measures include intermittent catheterization and anticholinergic medication. However, when conservative measures fail, surgical intervention may be indicated. Historically, the next step was major reconstructive surgery to create a low-pressure urinary reservoir. The introduction of intravesical botulinum neurotoxin A (BoNT/A) for use in children in 2002 offered a less invasive option for management. However, its exact role is still evolving.
Areas covered
This article summarizes the mechanism of action of BoNT/A for management of NDO and evaluates the current literature defining common practice and clinical efficacy in children with NDO. The findings of the recently completed phase III trial for intravesical onabotulinumtoxinA in children are discussed in detail.
Expert opinion
As the first BoNT/A approved for use in children with NDO, onabotulinumtoxinA appears to be a safe and less invasive alternative to major reconstructive surgery. However, data defining appropriate patient selection and its role as a long-term treatment option continue to develop.
Article highlights
Neurogenic detrusor overactivity causes involuntary detrusor contractions during bladder filling and storage that can transmit high pressures to the upper urinary tracts and/or lead to significant incontinence.
Initial management consists of clean intermittent catheterization and anticholinergic medication to maintain low intravesical pressures, but if these fail and renal function is at risk, surgical management may be indicated.
Botulinum neurotoxin A offers a less invasive option to maintain a low-pressure urinary reservoir compared to anatomy-altering reconstructive surgery. The toxin is generally injected into the bladder wall and acts to prevent acetylcholine release at the neuromuscular junction, leading to flaccid paralysis.
OnabotulinumtoxinA has been shown to be efficacious and safe after single and repeat injection cycles in children ≥5 years with neurologic dysfunction of the lower urinary tract in a large, phase III randomized control trial. However, its effect is temporary and requires repeat procedures at regular intervals to maintain effect.
Very few adverse events have been reported following intravesical botulinum neurotoxin A injection in children. Although apparently safe for use in this population, this may also reflect reporting bias.
Current literature questions the efficacy of botulinum neurotoxin A for use in fibrotic, end-stage bladders, as well as its role as a lifelong treatment option.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Abbreviations
BoNT | = | – Botulinum neurotoxin |
CIC | = | – Clean intermittent catheterization |
FDA | = | – Food and Drug Administration |
NDO | = | – Neurogenic detrusor overactivity |
SV2 | = | – Synaptic vesicle protein 2 |
SNAP 25 | = | – synaptosomal nerve associated protein 25 |
U | = | – Units |
UDS | = | – Urodynamic studies |
UI | = | – Urinary incontinence |
U.S.A. | = | United States of America |
UTI | = | Urinary tract infection |
Y | = | Years |