Use of botulinum toxin in individuals with neurogenic detrusor overactivity: state of the art review

Abstract

Background: Botulinum neurotoxin (BoNT) injection into the bladder wall has been shown to be an effective alternative to anticholinergic (antimuscarinic) medications and more invasive surgery in those with multiple sclerosis and spinal cord injury with neurogenic detrusor overactivity (NDO) and urinary incontinence who are not tolerating anticholinergic medications. In August 2011, Botox(®) (onabotulinumtoxinA) received Food and Drug Administration (FDA) approval for this use. Clinically, intradetrusor injection of BoNT has been found to decrease urinary incontinence and improve quality of life. Its impact on urodynamic parameters is an increase in the maximum cystometric (bladder) capacity and decrease in the maximum detrusor pressures. The most common side effects are urinary tract infections and urinary retention. There have been rare reports and a black box warning of distant spread of BoNT. BoNT has gained popularity because of its effectiveness and long duration of action, relative ease of administration, easy learning curve, reproducibility of results on repeated administration, and low incidence of complications.

Objective: To discuss the structure and function, mechanisms of action, clinical and urodynamic studies, injection technique, potential beneficial and adverse effects, and potential areas of research of BoNT.

Methods: Literature search focused on botulinum toxin in MEDLINE/PubMed. Search terms included botulinum toxin, neurogenic bladder, NDO, botox bladder, botox spinal cord injury, botox, FDA, botox side effects. All papers identified were English language, full-text papers. In addition, English abstracts of non-English papers were noted. The reference list of identified articles was also searched for further papers.

Conclusion: Botulinum toxin is an alternative treatment for individuals with NDO who fail to tolerate anticholinergic medications. Its popularity has increased because of the literature, which has supported its effectiveness, safety, easy use and learning curve, reproducibility of results on repeated use, and recent FDA approval of Botox(®) (onabotulinumtoxinA).

Figure 1

ACh-filled synaptic vesicles with an attached synaptobrevin protein. VAMP combine with SNAP 25 and syntaxin combine to form the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. This complex causes calcium influx, membrane depolarization, and ACh exocytosis from the presynaptic nerve terminal into the synaptic cleft.

Figure 2

Once the BoNT molecule complex (heavy chain and light chain attached by a disulfide bond) has entered into the neuron, the BoNT light chain disrupts the proteins that form the SNARE complex located at the presynaptic nerve terminal. This prevents the ACh-filled synaptic vesicles from attaching to the SNARE complex so that there is no membrane depolarization or exocytosis of the ACh from the presynaptic nerve terminal. Different serotypes of BoNT cleave different proteins of the SNARE complex.