nacin, are selective for the M3 receptor and thus offer the potential of reduced side-effects.

–Intravesical oxybutynin was shown to have increased efficacy and reduced side effects. Compared with oral oxybutynin, intravesical oxybutynin has more potent and longeracting detrusor suppressive effects with good tolerance and should be used prior to considering surgical therapies.

–The usual dose regimen of oral oxybutynin is 0.3–0.6 mg/kg per day in three doses.

–In children with insufficient response or significant systemic side effects to oral oxybutynin, intravesical instillation of oxybutynin has been shown to be a highly efficacious, reliable, and well-tolerated therapy for children who would otherwise require surgical therapy.

–Intravesical oxybutynin is used in dosages between 0.3 and 0.6 mg/kg per day in two or three doses. Given its better tolerability compared with oral treatment, if required, intravesical dosages can be further increased up to doses of 0.9 mg/kg per day.

•Tolterodine L-tartrate (Detrol and Detrol LA):

–Tolterodine L-tartrate is a competitive muscarinic receptor antagonist for overactive bladder.

–It differs from other anticholinergic types in that it has selectivity for urinary bladder over salivary glands.

–It exhibits high specificity for muscarinic receptors and has minimal activity or affinity for other neurotransmitter receptors and other potential targets such as calcium channels.

–In clinical studies, the mean decrease in urge incontinence episodes was 50 % and the mean decrease in urinary frequency was 17 %.

•Trospium (Sanctura):

–Trospium is a quaternary ammonium compound that elicits antispasmodic and antimuscarinic effects.

–It antagonizes acetylcholine effect on muscarinic receptors.

–Parasympathetic effect reduces smooth muscle tone in the bladder.

–Trospium is indicated to treat symptoms of overactive bladder (e.g., urinary incontinence, urgency, frequency).

•Fesoterodine (Toviaz):

–Fesoterodine is a competitive muscarinic receptor antagonist.

–The antagonistic effect results in decreased bladder smooth muscle contractions.

–It is indicated for symptoms of overactive bladder (e.g., urinary urge incontinence, urgency, and frequency).

11.10 Botulinum Toxin Type A

•It binds to the presynaptic nerve endings of cholinergic neurons, resulting in a marked reduction in bladder contractions.

•Botulinum A toxin injections into the detrusor muscle have been shown to be a potentially valuable approach in the neurogenic overactive bladder.

•It is also associated with reduced requirement for oral medication and improved quality of life.

•Urodynamic efficacy lasts for about 6 months, after which repeated injections are necessary.

•Repeated botulinum A toxin injections could be considered to postpone or avoid surgical procedures in the small minority of children not responding to standard therapy with CIC and anticholinergics.

•However, further investigations are required, given remaining concerns about costs and long-term efficacy and safety of prolonged botulinum A toxin administration.

11.11Tricyclic Antidepressant Drugs

•These drugs are used to treat major depression; however, they have an additional use that is treatment of bladder dysfunction.

•They function to increase norepinephrine and serotonin levels.

•In addition, they exhibit anticholinergic and direct muscle relaxant effects on the urinary bladder.

•Imipramine hydrochloride (Tofranil)

–Imipramine hydrochloride is a typical tricyclic antidepressant.

–It facilitates urine storage by decreasing bladder contractility and increasing outlet resistance.

–It has alpha-adrenergic effect on the bladder neck and antispasmodic effect on detrusor muscle.

–Imipramine hydrochloride has a local anesthetic effect on bladder mucosa.

•Amitriptyline hydrochloride (Elavil)

–Amitriptyline hydrochloride is a tricyclic antidepressant with sedative properties.

–It increases circulating levels of norepinephrine and serotonin by blocking their reuptake at nerve endings and is ineffective for use in urge incontinence.

–However, it is extremely effective in decreasing symptoms of urinary frequency in women with pelvic floor muscle dysfunction.

–Amitriptyline hydrochloride restores serotonin levels and helps break the cycle of pelvic floor muscle spasms.

•Infection:

–In the absence of reflux, patients with UTIs are treated symptomatically.

–Patients with vesicoureteral reflux are often placed on prophylactic antibiotics to reduce the chance of upper UTI or pyelonephritis.

–Bacteriuria is seen in as many as 55 % of patients who have received clean intermittent catheterization (CIC).

–Patients who are completely asymptomatic do not need treatment.

•Vesicoureteral Reflux (VUR):

–VUR occurs in 3–5 % of infants with myelodysplasia and is usually associated with detrusor hyperreflexia or DSD.

–Treatment consists of:

•Antibiotic prophylaxis to prevent infection

•Anticholinergic medications to lower detrusor filling and voiding pressures

•A method of bladder emptying, most commonly CIC

–In children with lower-grade reflux who empty their bladders completely, treatment may be limited to prophylactic antibiotics.

–In children with high-grade reflux, CIC is started to ensure complete emptying.

–Children unable to empty their bladders, regardless of reflux, are treated with CIC.

–Children with detrusor hyperreflexia (with or without hydronephrosis) are started on anticholinergic therapy to decrease intravesical pressures and possibly decompress the upper urinary tracts.

•Reflux treated in this manner has shown a dramatic response, resolving in 30–55 % of children.

•Avoid the Crede maneuver (voiding by suprapubic pressure) in children with reflux because it can increase pressures and aggravate the degree of reflux.

•Inability to empty bladder:

–Because most patients with myelodysplasia are unable to spontaneously empty their bladders, numerous methods have been devised to potentiate bladder emptying.

–CIC on a regular basis is a safe, effective method of emptying the bladder and, if performed under clean conditions, does not appear to significantly increase the risk of infection.

–The practice of CIC has changed the treatment of and approach to patients with neurogenic bladders.

–Currently, urinary diversion is rarely performed in pediatric patients.

•Incontinence:

–Medical therapy consists of anticholinergic medications to increase the functional bladder volume and to reduce involuntary contractions.

–Additionally, alpha agonists have been used infrequently in children to increase sphincter tone.

•Impaired bowel function:

–Often, children with myelodysplasia have disturbances of bowel as well as urinary function.

–This is managed most commonly with mild laxatives, such as mineral oil, combined

with enemas or digital stimulation to facilitate removal of bowel contents.

–Constipation can affect bladder emptying adversely

–The need for a program to combat constipation by maintaining soft stools and facilitating complete evacuation of bowel contents is an integral part of treatment in children with myelodysplasia.

•Consider all patients with myelodysplasia of spina bifida to have a latex allergy and make every effort to avoid exposure to latex from birth. Gloves, catheters, crib pads, and bottle nipples are all potential sources and may exacerbate hypersensitivity.

11.12 Surgical Management

•Surgery for neurogenic bladder, although once performed on most patients, is now primarily reserved for patients:

–Who have progressive renal damage despite maximal medical therapy

–With extremely noncompliant bladders

–Who wish to improve their continence

•Most procedures are designed to allow adequate low-pressure bladder storage (thereby protecting the upper urinary tract), to correct persistent reflux and prevent renal scarring, or to aid with continence.

•Procedures to correct vesicoureteral reflux:

–Ureteral reimplantation

•Ureteral reimplantation can be performed in patients with recurrent symptomatic UTIs despite adequate bladder drainage and antibiotic prophylaxis or in patients with persistent high-grade reflux with demonstrated renal scarring.

•The purpose of the procedure is to create a nonrefluxing connection between the ureter and the bladder.

•This treatment is very effective, provided that a regimen is implemented to ensure a low-pressure reservoir and bladder emptying.

–Dextranomer/hyaluronic acid (Deflux) injection

•This is a much less invasive way to address vesicoureteral reflux.

•Deflux (a viscous gel consisting of dextranomer microspheres and hyaluronic acid) is injected cystoscopically just beneath the ureteral orifice to prevent reflux.

•It is performed as an outpatient procedure with excellent success rates (70–85 % with a single injection) and can be repeated if necessary.

–Vesicostomy

•In infants who cannot be catheterized or who demonstrate worsening renal function despite medical therapy and CIC, cutaneous vesicostomy can be performed to establish adequate bladder drainage.

•Vesicostomy is an effective temporary procedure that may be reversed at any time.

•Bladder augmentation:

–Bladder augmentation is an option in patients with small bladder capacity and poor bladder compliance despite maximal medical therapy.

–The bladder capacity is increased by anastomosing a detubularized segment of bowel to the bladder. As a result of this, the storage pressures can be lowered, minimizing upper urinary tract deterioration and improving continence.

–This can be associated with complications including metabolic derangements, mucous production, stone formation, and hematuria.

–If incontinence is a significant problem, a bladder neck sling procedure can be performed along with bladder augmentation.

•Urinary diversion:

–Formal urinary diversion for neurogenic bladder is very rarely performed today.

–The risks of major abdominal surgery, metabolic derangements, and long-term upper

urinary tract deterioration are present with urinary diversion.

–Since the advent of CIC, some patients who underwent incontinent urinary diversion as infants have undergone successful undiversion with bladder augmentation.

•Procedures for incontinence:

–As patients get older, continence becomes an issue in their lives.

–Several procedures have been developed to improve continence, with the hope to promote more-independent living.

–Dextranomer/hyaluronic acid (Deflux) bladder neck injection

•This procedure consists of cystoscopically injecting dextranomer/hyaluronic acid into the bladder neck to increase outlet resistance.

•It has been shown to improve continence, but complete cures are unpredictable and the durability of the procedure is still being evaluated.

–Bladder neck sling

•This procedure entails placing a sling of either autologous tissue or synthetic polypropylene mesh beneath the urethra in order to increase outlet resistance.

•There are several variations to the procedure, but overall success rates range from 60% to greater than 85%, with a number of patients becoming fully continent.

–Detrusor myoplasty

•Though uncommon, this procedure has the possibility of increasing bladder contractility in some patients.

•It is performed by harvesting the patient’s latissimus dorsi muscle and microsurgically transplanting it so that it wraps around the bladder.

•This has allowed some patients to spontaneously void and reduce their dependence on catheterization.

–Stem cell injection

•This is still purely experimental, but preliminary studies have shown some promise.

•In this procedure, stem cells are cystoscopically injected into the urinary sphincter.

•The goal of therapy is to increase sphincter activity and improve continence.

Further Reading

1. Amark P, Bussman G, Eksborg S. Follow-up of longtime treatment with intravesical oxybutynin for neurogenic bladder in children. Eur Urol. 1998;34: 148–53.

2. Apostolidis A, Dasgupta P, Denys P, Elneil S, Fowler CJ, Giannantoni A, et al. Recommendations on the use of botulinum toxin in the treatment of lower urinary tract disorders and pelvic floor dysfunctions: a European consensus report. Eur Urol. 2009;55(1):100–19.

3. Baskin LS, Kogan BA, Benard F. Treatment of infants with neurogenic bladder dysfunction using anticholinergic drugs and intermittent catheterisation. Br J Urol. 1990;66:532–4.

4. Buyse G, Verpoorten C, Vereecken R, Casaer P. Treatment of neurogenic bladder dysfunction in infants and children with neurospinal dysraphism with clean intermittent (self) catheterisation and optimized intravesical oxybutynin hydrochloride therapy. Eur J Pediatr Surg. 1995;5:31–4.

5. Buyse G, Waldeck K, Verpoorten C, Björk H, Casaer P, Andersson KE. Intravesical oxybutynin for neurogenic bladder dysfunction: less systemic side effects due to reduced first pass metabolism. J Urol. 1998;160:892–6.

6. De Wachter S, Wyndaele JJ. Intravesical oxybutynin: a local anesthetic effect on bladder C afferents. J Urol. 2003;169:1892–5.

7. Edelstein RA, Bauer SB, Kelly MD, Darbey MM, Peters CA, Atala A, Mandell J, Colodny AH, Retik AB. The long-term urological response of neonates with myelodysplasia treated proactively with intermittent catheterization and anticholinergic therapy. J Urol. 1995;154:1500–4.

8. Fernandes E, Reinberg Y, Vernier R, Gonzales R. Neurogenic bladder dysfunction in children: review of pathophysiology and current management. J Pediatr. 1994;124:1–7.

9.Frenkl TL, Rackley RR. Injectable neuromodulatory agents: botulinum toxin therapy. Urol Clin N Am.

2005;32(1):89–99.

10. Goessl C, Sauter T, Michael T, Bergé B, Staehler M, Miller K. Efficacy and tolerability of tolterodine in children with detrusor hyperreflexia. Urology. 2000; 55:414–8.

11. Jeruto A, Poenaru D, Bransford R. Clean intermittent catheterisation: overview of results in 194 patients with spina bifida. Afr J Pediatr Surg. 2004;1:20–3.

12. Kaefer M, Pabby A, Kelly M, Darbey M, Bauer SB. Improved bladder function after prophylactic treatment of the high risk neurogenic bladder in newborns with myelomeningocele. J Urol. 1999;162: 1068–71.

13. Kasabian NG, Bauer SB, Dyro FM, Colodny AH, Mandell J, Retik AB. The prophylactic value of clean intermittent catheterization and anticholinergic medication in newborns and infants with myelodysplasia at risk of developing urinary tract deterioration. Am J Dis Child. 1992;146:840–3.

14. Kessler TM, Lackner J, Kiss G, Rehder P, Madersbacher H. Early proactive management improves upper urinary tract function and reduces the need for surgery in patients with myelomeningocele. Neurourol Urodyn. 2006;25:758–62.

15. Kurzrock EA, Polse S. Renal deterioration in myelodysplastic children: urodynamic evaluation and clinical correlates. J Urol. 1998;159:1657–61.

16.Madersbacher H. Neurogenic bladder dysfunction in patients with myelomeningocele. Curr Opin Urol. 2002;12:469–72.

17. McKibben MJ, Seed P, Ross SS, Borawski KM. Urinary tract infection and neurogenic bladder. Urol Clin N Am. 2015;42(4):527–36.

18.Snodgrass WT, Adams R. Initial urologic management of myelomeningocele. Urol Clin N Am. 2004;31:427–34.

19. Sutherland RS, Kogan BA, Baskin LS, Mevorach RA. Clean intermittent catheterization in boys using the LOFric catheter. J Urol. 1996;156:2041–3.

20. van Gool JD, Dik P, de Jong TP. Bladder sphincter dysfunction in myelomeningocele. Eur J Pediatr. 2001;160:414–20.

21. Wein AJ, Rackley RR. Overactive bladder: a better understanding of pathophysiology, diagnosis and management. J Urol. 2006;175(3 Pt 2):S5–10.

22. Zegers B, Uiterwaal C, Kimpen J, et al. Antibiotic prophylaxis for urinary tract infections in children with spina bifida on intermittent catheterization. J Urol. 2011;186(6):2365–71.