Use of Botulinum Toxin in Exstrophy

The management of children with exstrophy has changed significantly over the last several decades. It was not that long ago that urinary diversion with an ileal conduit, continent reservoir, or ureterosigmoidostomy was replaced by anatomic bladder reconstruction and the possible use of bladder augmentation as standard management for many children born with exstrophy. Achieving continence in this patient group remains a challenge.

Current standard therapy for the management of patients with exstrophy involves staged or integrated (complete) primary anatomic reconstruction. Following these efforts, children are followed closely with further medical or surgical intervention as indicated. Urinary incontinence can be caused by an inadequate urethral sphincter function, low bladder capacity, and/or bladder instability. Treatment for incontinence is tailored to the underlying cause(s) of incontinence as a result.

For those unresponsive to standard management for bladder instability, botulinum-A toxin administered as intravesical injection may be an option as an alternative to surgical treatment options such as enterocystoplasty (bladder augmentation) Although life-saving in many respects, bladder augmentation introduces life-long risks of its own including an increased long-term risk of malignancy, bladder stones, metabolic imbalance, and rupture of the augment. Currently, our management goal is to decrease the need for bladder augmentation while achieving continence and a safe urinary tract.

Botulinum toxin A (also known as BotoxR in the United States and DysportR in Europe) is derived from a bacteria, Clostridium botulinum. It is a potent neurotoxin that paralyzes muscles by preventing transmission of nerve signals from the end of the nerves to the muscles. It does this by blocking the release of acetylcholinsterase in a noncompetetive fashion. The effects of the neurotoxin can last for months. Botulinum toxin A is used medically to treat skeletal muscular spasticity associated with cerebral palsey or blepharospasm. It is used cosmetically to reduce the appearance of wrinkles.

Several clinical studies have demonstrated botulinum-A toxin can be used successfully to treat bladder spasticity caused by neurogenic bladder conditions in both children and adults. [1-6] These studies also have shown the use of botulinum toxin-A for neurogenic bladder conditions to be safe.

Botulinum toxin-A injection also may play an important therapeutic role in a select group of patients with refractory bladder instability unresponsive to standard therapy with anticholinergic medications. Botulinum toxin A also has been used to treat refractory urge urinary incontinence caused by bladder hyperactivity in adults.

For patients with exstrophy who have urinary incontinence at least partly attributed to bladder overactivity, botulinum toxin A can be considered a treatment option. Urge urinary incontinence is characterized by the overwhelming urge to urinate without the ability to stop it from happening. The diagnosis is usually confirmed by urodynamic evaluation. The first line of therapy involves oral or topical anticholinergic medications like oxybutinin, tolterodine, or hyoscamine.

A patient would be a candidate for botulinum toxin A if these medications are not effective or if the medications are poorly tolerated. Botulinum toxin A is adminstered by direct cystoscopic injection just under the lining of the bladder in 20 to 30 different locations in the bladder. The effect of the injections may take days to weeks and typically last 6 to 12 months. One of the potential adverse side-effects of botulinum toxin-A injection is urinary retention that could require catheterization to empty the bladder. Botulinum toxin A remains a novel treatment choice for urianry incontinence. The best application of botulinum toxin A remains a question to be answered.

Richard Grady MD CRHMC, 11.08

1. Schurch, B., D.M. Schmid, and M. Stohrer, Treatment of neurogenic incontinence with botulinum toxin A. N Engl. J. Med. 2000. 342(9): p. 665.

2. Mall, V., et al., Treatment of neuropathic bladder using botulinum toxin A in a 1-year-old child with myelomeningocele. Pediatr. Nephrol. 2001. 16(12): p. 1161-2.

3. Schulte-Baukloh, H., H.H. Knispel, and T. Michael, Botulinum-A toxin in the treatment of neurogenic bladder in children. Pediatrics , 2002. 110(2 Pt 1): p. 420-1.

4. Smith, C.P., G.T. Somogyi, and M.B. Chancellor, Emerging role of botulinum toxin in the treatment of neurogenic and nonneurogenic voiding dysfunction. Curr. Urol. Rep. 2002. 3(5): p. 382-7.

5. Grosse, J., G. Kramer, and M. Stohrer, Success of repeat detrusor injections of botulinum a toxin in patients with severe neurogenic detrusor overactivity and incontinence. Eur. Urol. 2005. 47(5): p. 653-9.

6. Bagi, P. and F. Biering- Sorensen, Botulinum toxin A for treatment of neurogenic detrusor overactivity and incontinence in patients with spinal cord lesions. Scand. J. Urol. Nephrol.