Botulinum-A toxin for pediatric neurogenic bladder dysfunction

Three clinical trials are underway at St. Louis Children’s Hospital and Washington University School of Medicine to evaluate the long-term effectiveness of Botulinum-A toxin (Botox) for the treatment of overactive bladder and urinary incontinence in children under age 18.

St. Louis Children’s Hospital, a worldwide center for pediatric incontinence research and treatment, is building upon more than a decade of clinical research focused on the use of Botox in the pediatric population. Botox was approved in 2012 by the Food and Drug Administration to treat overactive bladders in adults and has been evaluated here for use in children since 2006.

Pediatric urologist Paul Austin, MD, professor of urologic surgery, is an international leader in the evaluation and use of Botox in children. His research has shown that Botox can play a significant role in the treatment of overactive or spastic bladders in children, particularly those diagnosed with neurogenic bladder dysfunction as a result of congenital neural tube defects such as spina bifida. He was among a handful of pediatric urologists who first evaluated Botox injections into the bladder wall. He now is a leading authority on a more novel use of Botox:  injecting it into the external urethral sphincter.

In a longitudinal study published recently in the Journal of Urology, Austin found that two-thirds of young patients that failed urotherapy and medical management and subsequently underwent Botox injections into the external urinary sphincter saw significant improvement in bladder control. Patients in the study, treated between 2006 and 2012, ranged from age 4 to 19.

“The vast majority of children respond to standard therapy, such as anti-cholinergic medications,” Austin says. “But if they have refractory dysfunctional voiding or if they develop significant side effects from the use of anti-cholinergic drugs, they can be a candidate for Botox.”

In the neurogenic patient population, overactive or spastic bladder is fairly common. At St. Louis Children’s Hospital, the Pediatric Urology clinic sees approximately 1,000 patients annually with lower urinary tract dysfunction. A subset of those will be unresponsive to bladder relaxant medications. Some may develop a stiff or rigid bladder that makes it difficult to void entirely, resulting in an increase in storage pressure within the bladder, a complication that significantly increases the risk for renal damage.

“You have to be more aggressive in managing bladder dysfunction to avoid that elevated risk of a deterioration in kidney function or, worse, renal failure,” he says. “So there are really two criteria I use for Botox — children with elevated bladder pressure and those who have bladder over-activity who are nonresponsive to other urotherapy.”

Some patients require more than one Botox injection to treat their incontinence. The ability to use this minimally invasive procedure, though, has proven to increase overall patient satisfaction and quality of life.

“In my patients, there are the accompanying issues of low self-esteem, anxiety or depression about incontinence. Secondly, there are a lot of hygiene issues resulting from incontinence, such as excoriated skin or infections, which can impact health and daily living,” Austin says. “One of the most rewarding aspects of caring for children with incontinence is seeing them in dry underwear for the first time in their life. They are making eye contact with me and holding their head up high. It’s a huge, positive change in children, especially those who are school age and who want to spend time with their friends without worrying about incontinence issues.”

Austin cautions that even with the significant positive outcomes noted in his multiple studies, approximately 20 percent of spina bifida patients will fail to respond to either standard urotherapy or Botox. In those cases, surgical intervention should be considered, such as enterocystoplasty or the Mitrofanoff procedure, which uses a portion of the appendix to create an outflow port from the bladder.

Austin, who has spent his entire career on pediatric incontinence issues and is the current General Secretary of the International Children’s Continence Society, says, “To avoid significant complications such as renal disease, any child with neurogenic bladder should be referred to a specialist. In our experience at St. Louis Children’s Hospital, we have found that Botox will either prevent those kids from needing bladder augmentation entirely or it may bridge and extend the time as to when such a procedure is needed.”