What are botulinum toxin injections to treat neurogenic detrusor overactivity?

Updated: Mar 06, 2019
  • Author: Pamela I Ellsworth, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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This topic addresses the use of botulinum toxin injections to treat neurogenic detrusor overactivity (NDO). Various neurologic conditions may cause detrusor overactivity and urinary incontinence. In select conditions, such as spinal cord injury, the attendant risk of upper tract deterioration exists as a result of pyelonephritis and increased intravesical pressure as a result of poor bladder compliance and detrusor sphincter dyssynergia.

Initial management of patients with detrusor overactivity related to a neurologic condition consists of behavioral therapy, when feasible, and anticholinergic therapy. In those patients with increased postvoid residuals, clean intermittent catheterization is often used in conjunction with anticholinergic therapy.

However, the side effects of anticholinergic therapy have led to poor compliance with long-term use. In attempts to improve the efficacy and tolerability of anticholinergic therapy, several newer therapies have been developed that are available in sustained-release formulations and variable doses.

Despite these modifications, patients whose response to anticholinergic therapy may be unsatisfactory in terms of either efficacy or tolerability exist. Historically, such individuals were faced with more invasive surgical interventions to lower detrusor pressure or promote continence, including bladder augmentation. Bladder augmentation is not without significant long-term risks, including infections, stones, malignancy, and perforation.

A form of botulinum toxin A known as onabotulinumtoxinA (BOTOX; Allergan, Irvine, CA) has been approved by the US Food and Drug Administration (FDA) for the treatment of urinary incontinence due to NDO in adults who have an inadequate response to or are intolerant of anticholinergic therapy.

Botulinum toxin A blocks neuromuscular transmission by binding to acceptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. The inhibition occurs as the neurotoxin cleaves synaptosomal-associated protein 25 (SNAP-25), a protein critical to the successful docking and release of acetylcholine from presynaptic vesicles located within the nerve endings.

When injected into the muscle at therapeutic doses, botulinum toxin A produces partial chemical denervation of the muscle, resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy, axonal sprouting may occur, and extra junctional acetylcholine receptors may develop. Evidence exists that reinnervation of the muscle may occur, thus slowly reversing the muscle denervation produced by botulinum toxin A.

Also proposed is that the effect of botulinum toxin A on detrusor overactivity may be related to its effect on sensory receptor expression in suburothelial fibers. [1] The expression of TRPV1, P2X3, substance P, and calcitonin gene-related peptide by these fibers has also been proposed to play a role in the pathophysiology of detrusor overactivity. [1] Decreased levels of TRPV1 and P2X3-IR have been demonstrated in submucosal biopsies obtained after intravesical injection of botulinum toxin A. [1]

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