Curr Urol Rep (2011) 12:413–418 DOI 10.1007/s11934-011-0218-9
Updates in the Management of the Overactive Bladder in Patients with Myelomeningocele
OVERACTIVE BLADDER (GOPAL BADLANI, SECTION EDITOR)
Gregory E. Dean & Christopher Long
Published online: 25 October 2011 # Springer Science+Business Media, LLC 2011
G. E. Dean (*) : C. Long Department of Urology, Temple University, Philadelphia, PA 19140, USA e-mail: gedean951@hotmail.com
G. E. Dean 120 Carnie Boulevard, Suite 2, Voorhees, NJ 08043, USA
Abstract Overactive bladder secondary to myelomeningo- cele provides a unique management problem to the health care provider. A randomized prospective trial has called into question the standard postnatal treatment closure of myelomeningocele, with antenatal closure acting as an acceptable alternative, although caution for maternal and fetal risks must be further delineated. While traditional techniques such as the Mitrofanoff procedure have become standard of care in allowing patient independence from care providers, modifications of the technique in addition to assimilation of minimally invasive approaches have further improved quality-of-life measurements for this patient population. Intravesical botulinum-toxin injection therapy has provided acceptable outcomes, albeit transiently, in terms of improving bladder compliance and decreasing bladder pressures. Bladder neck revision, both endoscopi- cally and surgically, have shown promise with minimal upper tract deterioration. Nerve rerouting for neurogenic bladder is a novel, albeit unproven, approach, its use remaining experimental at this point. Utilization of the multitude of emerging techniques will serve to optimize treatment in this otherwise complicated patient population, although consideration of the long-term consequence of each therapy has yet to be elucidated.
Keywords Overactive bladder . Myelomeningocele . Botulinum toxin injection . Mitrofanoff procedure . Malone procedure . Bladder neck reconstruction . Sacral neuromodulation . Bladder rerouting
Introduction
Myelomeningocele is the most common cause of congenital neurologic anomalies compatible with life. Its incidence has decreased with the advent of folate supplementation as well as antenatal screening, and now has a prevalence of 3.1 per 10,000 live births in the United States [1]. The urologic management of patients with spina bifida remains complex and much remains to be elucidated regarding ideal management of this complex issue. Despite these chal- lenges, new data related to the etiology and management of these patients continue to emerge. The past year has seen the publication of a landmark article demonstrating the potential advantage of antenatal closure of myelomeningo- cele as well as several other notable publications applicable to this condition. This review will summarize these recent advances and identify directions for further development.
Antenatal Intervention
The recent publication of the Management of the Myelo- meningocele Study (MOMS) [2••] has provided a signifi- cant step forward in the management of patients with spina bifida. This multicenter collaborative study between the Children’s Hospital of Philadelphia, Vanderbilt University Medical Center, and the University of California, San Francisco, with data analysis support provided by George Washington University, demonstrated the potential advan- tage of antenatal myelomeningocele closure as opposed to standard postnatal closure. This prospective randomized
study accumulated patients from February 2003 and December 2010 and randomly assigned them to either prenatal or postnatal closure. Among the inclusion criteria were a singleton pregnancy, myelomeningocele with an upper boundary between T1 and S1, a gestational age between 19 and 26 weeks, and evidence of hindbrain herniation. Among the exclusion criteria were maternal body mass index of 35 or more, severe kyphosis, any other major fetal anomalies, and high risk of preterm labor. While this study was being conducted, there was a moratorium preventing other centers from performing fetal myelome- ningocele closure, thereby improving the quality of this watershed study. All children underwent physical, neuro- logic, and developmental exams at the ages of 12 and 30 months to determine whether any difference in outcomes existed. Maternal, fetal, and neonatal secondary outcomes also were evaluated. These included the presence of Chiari II malformations, the presence of maternal or fetal surgical complications, and mortality. Other factors examined included the time to placement of a ventriculoperitoneal shunt, the ability to ambulate, and the presence or degree of physical disability. A total of 183 eligible women underwent random assignment during the study, which closed early due to efficacy of prenatal intervention.
The results of the study demonstrated that by the first year of life, 98% of the children treated with postnatal closure required shunting, compared to 68% of those patients    who    had    undergone    prenatal    closure    (P < 0.001). The incidence and degree of hindbrain herniation also was lower in the prenatal surgery group. Prenatal intervention resulted in a level of function that was two or more levels better than anticipated by anatomic prediction (32% vs 12%). The prenatal surgery group also exhibited better motor function and were more likely to walk without orthotics (42% vs 21%). Ability for self-care was improved in this group, although no difference in cognitive ability was demonstrated.
Risks associated with this approach included an in- creased incidence of premature delivery (mean gestational age of 34 vs 37 weeks). Of patients in the prenatal surgical group, 13% delivered before 30 weeks gestation, whereas none of the postnatal group delivered before 30 weeks. Other risks associated with prenatal surgery included chorioamniotic separation (26%), an increased risk of blood transfusion at delivery, and evidence of uterine wall thinning in the mother.
Urologic parameters, including need for clean intermit- tent catheterization, continence status, or bladder wall changes, were not examined. Notably, a subset of those patients who had undergone prenatal closure was studied by separate authors due to geographic proximity [3]. This limited nonrandomized study found that prenatal closure was associated with complete denervation of the external
sphincter and detrusor overactivity in all five patients. The results were compared to a similar cohort of postnatally closed patients, in which they found a complete denervation rate of 39% and detrusor overactivity of 38%. The authors cautioned that patients undergoing intervention required early and close urodynamic evaluation. Countering these concerns is an earlier study from Vanderbilt University that demonstrated that patients who had undergone prenatal closure had identical urodynamic parameters when com- pared to those who had undergone postnatal closure [4]. The MOMS report likely will encourage continued prenatal closure of patients with spina bifida, and it will be important to define any potential long-term urologic side effects of this approach to more clearly answer the question of the appropriate time for bladder closure intervention.
Botulinum Toxin Therapy
Several papers exploring the developing role of intravesical botulinum toxin injection for the treatment of the neuro- genic bladder have emerged. One of the more novel articles described the use of electromotive botulinum toxin in the treatment of children with myelomeningocele [5&#8226;]. In this study, 15 children (mean age 7.8 years) had 10 IU/kg of electromotive botulinum toxin type A delivered via transurethral catheter into a distended bladder. While connected to the catheter and two dispersive pads, a pulsed current generator delivered 10 mA for a total of 15 min. Urodynamic parameters then were measured to assess maximal bladder capacity, maximal detrusor pressure, and end-filling pressure. The urine and fecal continence status as well as vesicoureteral grade were evaluated at several time points, including before and at 1, 4, and 9 months post-treatment. The mean maximal bladder capacity in- creased    significantly    from    121 ± 39    mL    to    262 ± 41    mL    (P < 0.001). In addition, treatment resulted in a decrease of mean maximal    detrusor    pressure    from    75 ± 16    cm    H2O    to    39 ± 10 cm H2O and a reduction in the pressure at maximum capacity from 22±7 cm H2O to 13±2 cm H2O after treatment. Improvement in urinary incontinence score was seen in 80% of patients. The reflux grade decreased in 7 of the 12 children (mean vesicoureteral reflux [vur] grade 2.25 ±1.3 vs 1.37±0.7; P=0.001). Complications were limited to skin erythema and a burning sensation, noted in 6 of 15 children.
This approach is notable in that it offers the potential for a treatment protocol that avoids general anesthesia. One of the barriers to long-term and widespread adoption of botulinum toxin for the treatment of patients is the need for retreatment, and hence, exposure to general anesthesia, every 6 to 12 months. Should the electromotive approach prove to be as effective as injection therapy, the avoidance
of general anesthesia normally required in children would make this technique very attractive. A related publication that examined the histologic distribution of botulinum toxin in rabbits treated with the same electromotive technique noted even distribution within the urothelium, interstitium, and muscularis layers of the bladder, suggesting that this delivery system is effective [6].
Another paper looking at a more traditional approach examined the role of injecting botulinum toxin into the detrusor muscle and compared it with detrusor therapy plus additional injection into the urethral sphincter [7]. Both techniques resulted in improvement in bladder capacity, maximal detrusor pressure, and detrusor sphincter dyssy- nergia at 3 and 6 months, but postvoid residual was significantly less in the group who also underwent sphincteric injection. While this may be of benefit in select populations, most patients with myelomeningocele are on intermittent catheterization, minimizing the benefit of a reduced postvoid residual.
While the benefits of detrusor botulinum toxin injection in patients with spina bifida and neurogenic bladder are well recognized, this may not be a panacea for all patients with poor detrusor compliance. A study looking at a group of 11 children with impaired compliance secondary to neuropathic bladder dysfunction were treated with intra- vesical botulinum toxin injection and evaluated with urodynamics at 3- and 12-months post-treatment. At 3 months postinjection, bladder pressures decreased by 17% and bladder capacity increased by 33%; however, compliance remained poor in all but one patient. Indeed, at 12-month evaluation, patients still were experiencing effects of botulinum toxin, but values were approaching preinjection levels, although repeat injections were equally effective [8&#8226;]. These findings support the notion that once fibrotic changes secondary to deposition of collagen occurs, reversing these changes becomes difficult.
While this may be the case after severe fibrosis has occurred, evidence that treatment does not result in progression of fibrosis, or may in fact decrease it in those patients undergoing multiple treatments, has come to light [9, 10&#8226;&#8226;]. This study [9] examined bladder biopsies of 40 children between the ages of 2 and 18 years in conjunction with detrusor injection with botulinum toxin type A. All had neurogenic bladder dysfunction that had failed conser- vative management and exhibited leak point pressures greater than 40 cm H20. Biopsies were performed at the time of injection and were stratified according to number of prior injections; those with the greatest number of injections were noted to have a decrease in the amount of inflamma- tion and fibrosis. Unfortunately, these biopsies were not matched against the same patient over time (comparisons were made to different patients), so a selection bias may have been present.
In virtually all protocols employing intravesical injections of botulinum toxin, the trigone has been spared, based on fear of iatrogenic VUR. Despite this clinical pattern, little evidence exists to support the elimination of the trigone in injection therapy. Recent evidence has challenged the theory that botulinum toxin acts via blockade of presynaptic cholinergic transmission, suggesting a more global blockade of both sensory and motor pathways, as well as direct muscle effects, as the mechanism of action. This blockade occurs through inhibition of neurotransmitters and neuropeptides as well as downregulation of the expression of capsaicin and purinergic receptors on afferent neurons [10&#8226;&#8226;]. The trigone is rich in sensory fibers with muscles sensitive to small changes in pressure [11]. This information led one group to hypothesize that injection into the trigone may be beneficial, prompting a prospective randomized trial of 36 adult patients with neurogenic bladder due to spinal cord injury, subjected to botulinum toxin A injection of either 300 IU into the detrusor only or 200 IU into the detrusor and 100 IU into the trigone [12]. A significant improvement was seen in those patients whose treatment included the trigone injection. Complete continence was achieved in 66.7% of those treated with trigone injection compared to 33.3% of those with only detrusor    injection    (P < 0.001).    Those    in    the    trigone-injected group also required less oral anticholinergic therapy, im- proved continence, and improved quality-of-life scores. Importantly, no patient experienced new-onset VUR or exacerbation of preexisting VUR [12]. This provocative study suggests that patients who do not undergo trigone injection in conjunction with detrusor injection of botulinum toxin may be inadequately treated.
Standard detrusor injection of botulinum toxin also has been shown to correct VUR in children with neurogenic bladders who have failed prior endoscopic Deflux (Oceana Therapeutics, Ltd., Dublin, Ireland) therapy. This study looked at 13 children (mean age of 5.3 years) with myelomeningocele, refractory neurogenic bladder, and VUR [13]. All patients received intradetrusor injection of botuli- num toxin A in addition to submucosal Deflux injection. The authors reported significant increases in bladder capacity, decreased maximal detrusor pressure, complete continence between catheterizations for 7 of 8 patients, and a remarkable 95% of VUR resolution. These results were confounded by the addition of the Peristeen anal irrigation system (Coloplast UK Ltd., Peterborough, England, United Kingdom) into the treatment protocol, although suggest that combination therapy is possible, safe, and effective.
Sacral Neuromodulation
Sacral neuromodulation has been utilized for sphincter disorders in adults, but few studies have specifically
addressed its utility in the pediatric population. Haddad et al. [14] performed a multicenter, open-label, randomized, crossover study in children over 5 years, and found sacral neuromodulation to be effective in patients with both bladder and bowel dysfunction. A total of 33 children were randomly assigned after a satisfactory trial period and device implantation. Bladder capacity improvement was the sole significant urodynamic improvement, while bladder overactivity and clinical response rate were significantly improved with modulation. A total of 10 patients with spina bifida were among the study population, although no specific subgroup analysis was provided. Complication rate was 18.8%, with two infection events and two electrode migrations, all requiring surgical intervention [14]. This study proposed the potential utility of a less invasive method as treatment of urinary and fecal incontinence, although long-term effectiveness and complications remain to be elucidated.
Rerouting
Initially developed in China, bladder rerouting is a novel procedure that creates an artificial somatic–autonomic reflex arc to restore neurologic control of bladder filling and emptying in patients with spina bifida [15]. In summary, a midline approach exposes the lumbar and sacral spinal column and a limited laminectomy is performed between L4 and S2. After identification of the L5 and S3 vertebral roots, the arc is created by anastomos- ing the proximal end of the ventral root of L5 to the distal end of the ventral root of S3. Xiao et al. [15] reported a success rate in 87% of 110 patients at 1 year of follow-up, with nearly all patients achieving continence. Peters et al. [16] were the first group in North America to report their experience with the technique. A total of nine patients enrolled in the study, with seven patients experiencing a response in bladder pressure with dermatome stimulation (suggesting successful rerouting). All patients were able to remain off antimuscarinic therapy postoperatively, although no patients achieved complete continence. The authors also noted improved bowel function for the patient population. Nearly all participants experienced increased bladder and bowel sensation, although consistent improvement docu- mented by urodynamic analysis was lacking [16]. Motor weakness of L5 is a complication highlighted in both studies, ranging from partial weakness (that eventually was shown to recover) to persistent full foot drop [15, 16]. While this approach promises much, no recent published studies have confirmed the degree of success reported by Xiao et al. [15]. Caution should be employed by any clinician who pursues this approach given the lack of confirming data at this point in time.
Surgical Approach
The advent of the Mitrofanoff procedure [17] changed the course of bladder management in patients with spina bifida, allowing independent catheterization in many patients in whom it otherwise would not be possible. As the use of this technique has been widely adopted, derivatives of the technique have emerged. The extravesical reimplantation of the appendix simplifies this procedure and has been used by many to facilitate ease of construction of this continent channel, particularly when bladder augmentation is not required. The Indiana group has cataloged their approach using this technique and provided insight into this applica- tion [18&#8226;&#8226;]. Of their 394 continent catheterizable channels performed between 1999 and 2009, 84 were performed extravesically. The channel was constructed using the appendix in 47 and a Monti ileovesicostomy in 37 of patients. The extravesical technique theoretically reduces patient morbidity by reducing the cystotomy and, therefore, hematuria and bladder spasm. Of note was that the incidence of complications was no greater in those who underwent an extravesical reimplant, with a 26% surgical revision rate.
Assessment of urologic management of patients with myelomeningocele includes the suggestion by Snodgrass et al. [19] that bladder augmentation may be overutilized. This paper reviewed the experience of 26 patients who had undergone a 360° fascial wrap around the bladder neck with appendicovesicostomy but without augmentation. These patients were followed for a mean of 39 months, with the authors noting that none of the patients subse- quently required bladder augmentation. Some of the patients initially demonstrated uninhibited contractions, but subsequently responded to aggressive anticholinergic therapy. None of the patients demonstrated evidence of trabeculation, reflux, or hydronephrosis on cystoscopy. All patients had detrusor areflexia and had diminished leak point pressures. The authors challenge the commonly held belief that corrective bladder outlet reconstruction may place the patient with a neurogenic bladder and open bladder neck at risk of upper tract deterioration. While this is a provocative perspective, the paper is not completely convincing in light of incontinence or incomplete conti- nence in 38.5% of their patients. These patients were not subject to the full bladder pressures that a therapeutic continence procedure achieves. Recognition of the incom- plete nature of continence achieved by the fascial wrap was recognized by a follow-up article describing improved continence by adding a Leadbetter-Mitchell procedure to the bladder wrap in an attempt to further improve continence [20]. We recently described a minimally invasive suburethral sling for the treatment of the incom- petent bladder neck [21] and have witnessed deterioration
of bladder capacity and compliance in one patient who has undergone this procedure. With this in mind, continued due diligence in monitoring for signs of deterioration in any patient with a neurogenic bladder undergoing a bladder outlet reconstruction is warranted.
The theme of bladder augmentation in children with spina bifida continues with the careful analysis of the effect that this technique has on serum chemistry [22&#8226;]. This paper provided a longitudinal analysis of serum chemistry on 113 patients who had undergone intestinal bladder augmentation. The patients were matched with their preoperative values to act as their own controls. Of note was that augmentation had no effect on serum pH, serum bicarbonate levels, partial pressure of CO2, or electrolytes, and the authors highlighted that no patient developed metabolic acidosis. These data run counter to the traditional understanding of the metabolic effects of interposing bowel in the urinary tract with the expected absorption of chloride and ammonium with the matching loss of bicarbonate. While these results are surprising, it was noted by the authors that no patients with renal insufficiency were included in the study. They suggest full work-up for patients developing metabolic acidosis after bladder augmentation, suggesting that it should no longer be attributed to enteroplasty.
A recent paper from Atlanta explored a minimally invasive approach to urinary and fecal continence in patients with an open bladder neck by combining an antegrade bladder neck bulking procedure with a Malone procedure [23]. This was an expansion of our earlier paper, which first described the use of antegrade bladder neck bulking in a pediatric population [24]. While the addition of the laparoscopic antegrade continence enema is a reason- able approach, in our own hands, we maintain the opinion that endoscopic bulking as simply a temporizing measure for most patients before a more definitive outlet-resistance procedure. This was brought about by our findings that while some measure of continence can be achieved in 80% of patients, 1.6 injection procedures per year on average are required to maintain this result. In the face of the very high cost of the bulking agent used (Deflux) and an average of 5 mL injected per treatment, this therapeutic approach is cost-prohibitive when compared to other techniques that do not require periodic reinjection.
While endoscopic bulking may have a limited long-term success in its current iteration, the role of the Malone procedure in improving the quality of life in these patients is quite clear. A study from Turkey demonstrates that in a group of 32 patients who had undergone an ACE procedure, all but 1 reported an improvement in quality of life. Stomal stenosis was the most commonly reported complication, followed by stomal leakage, but overall there was a significant improvement in continence [25].
Conclusions
The past year has seen many new developments in the treatment of neurogenic bladder in children with myelome- ningocele. Arguably, the most significant was the report of the randomized, prospective, blinded study examining the role of prenatal closure on functional outcomes. While no direct bladder effects were noted, time will tell whether this management helps or impedes bladder health. Many of the other papers discussed employed a minimally invasive approach that mirrors the current direction of urologic practice. While this direction is appropriate when therapeutic outcomes improve, care must be taken to continue to be proactive in the treatment of this difficult patient population.
Disclosures    No potential conflicts of interest relevant to this article were reported.
References
Papers of particular interest, published recently, have been highlighted as: &#8226; Of importance, &#8226;&#8226; Of major importance
1. Shin M, Besser LM, Siffel C, Kucik JE, Shaw GM, Lu C, et al. Prevalence of spina bifida among children and adolescents in 10 regions in the United States. Pediatrics. 2010;126(2):274–9.
2. &#8226;&#8226; Adzick NS, Thom EA, Spong CY, Brock JW, 3rd, Burrows PK, Johnson MP, et al. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011 Mar 17;364 (11):993–1004. This prospective randomized trial compared prenatal myelomeningocele repair to standard postnatal closure. Prenatal intervention resulted in decreased rate of shunting, albeit with increased maternal and fetal risks.
3. Koh CJ, DeFilippo RE, Borer JG, Khoshbin S, Bauer SB. Bladder and external urethral sphincter function after prenatal closure of myelomeningocele. J Urol. 2006;176(5):2232–6.
4. Holzbeierlein J, Pope JI, Adams MC, Bruner J, Tulipan N, Brock 3rd JW. The urodynamic profile of myelodysplasia in childhood with spinal closure during gestation. J Urol. 2000;164(4):1336–9.
5. &#8226; Kajbafzadeh AM, Ahmadi H, Montaser-Kouhsari L, Sharifi-Rad L, Nejat F, Bazargan-Hejazi S. Intravesical electromotive botulinum toxin type A administration–part II: Clinical application. Urology. 2011 Feb;77(2):439–45. The authors describe a novel technique for intravesical instillation of botulinum toxin that does not require general anesthesia and suggests improvements in bladder function parameters similar to direct detrusor injection therapy.
6. Kajbafzadeh AM, Montaser-Kouhsari L, Ahmadi H, Sotoudeh M. Intravesical electromotive botulinum toxin type A administration: part I–Experimental study. Urology. 2011;77(6):1460–4.
7. Safari S, Jamali S, Habibollahi P, Arshadi H, Nejat F, Kajbafzadeh AM. Intravesical injections of botulinum toxin type A for management of neuropathic bladder: a comparison of two methods. Urology. 2010;76(1):225–30.
8. &#8226; Horst M, Weber DM, Bodmer C, Gobet R. Repeated Botulinum-A toxin injection in the treatment of neuropathic bladder dysfunction
and poor bladder compliance in children with myelomeningocele. Neurourol Urodyn. 2011 Jun 14. The authors examined effects of botulinum toxin on detrusor muscle, and found no evidence of fibrosis or inflammation, even with increased number of injections.
9. Pascali MP, Mosiello G, Boldrini R, Salsano ML, Castelli E, De Gennaro M. Effects of botulinum toxin type a in the bladder wall of children with neurogenic bladder dysfunction: a comparison of histological features before and after injections. J Urol. 2011;185 (6 Suppl):2552–7.
10. &#8226;&#8226; Apostolidis A, Jacques TS, Freeman A, Kalsi V, Popat R, Gonzales G, et al. Histological changes in the urothelium and suburothelium of human overactive bladder following intradetru- sor injections of botulinum neurotoxin type A for the treatment of neurogenic or idiopathic detrusor overactivity. Eur Urol. 2008 Jun;53(6):1245–53. The authors examined bladder biopsies in conjunction with botulinum-toxin injection therapy and reported no evidence of fibrosis. They also found the mechanism of botulinum-toxin effects to be more global than originally thought.
11. Klein LA. Urge incontinence can be a disease of bladder sensors. J Urol. 1988;139(5):1010–4.
12. Abdel-Meguid TA. Botulinum toxin-A injections into neurogenic overactive bladder–to include or exclude the trigone? A prospective, randomized, controlled trial. J Urol. 2010;184(6):2423–8.
13. Neel KF. Total endoscopic and anal irrigation management approach to noncompliant neuropathic bladder in children: a good alternative. J Urol. 2010;184(1):315–8.
14. Haddad M, Besson R, Aubert D, Ravasse P, Lemelle J, El Ghoneimi A, et al. Sacral neuromodulation in children with urinary and fecal incontinence: a multicenter, open label, randomized, crossover study. J Urol. 2010;184(2):696–701.
15. Xiao CG. Reinnervation for neurogenic bladder: historic review and introduction of a somatic-autonomic reflex pathway procedure for patients with spinal cord injury or spina bifida. Eur Urol. 2006;49 (1):22–8. discussion 8–9.
16. Peters KM, Girdler B, Turzewski C, Trock G, Feber K, Nantau W, et al. Outcomes of lumbar to sacral nerve rerouting for spina bifida. J Urol. 2010;184(2):702–7.
17. Mitrofanoff P. Trans-appendicular continent cystostomy in the management of the neurogenic bladder. Chir Pediatr. 1980;21 (4):297–305.
18. &#8226;&#8226; VanderBrink BA, Kaefer M, Cain MP, Meldrum KK, Misseri R, Rink RC. Extravesical implantation of a continent catheterizable channel. J Urol. 2011 Jun;185(6 Suppl):2572–5. The authors note that extravesical catheterizable channel is feasible with acceptable complication rate. Patients have the benefit of less-invasive procedure and, theoretically, less hematuria and bladder spams.
19. Snodgrass W, Barber T, Cost N. Detrusor compliance changes after bladder neck sling without augmentation in children with neurogenic urinary incontinence. J Urol. 2010;183(6):2361–6.
20. Snodgrass W, Barber T. Comparison of bladder outlet procedures without augmentation in children with neurogenic incontinence. J Urol. 2010;184(4 Suppl):1775–80.
21. Dean GE, Kunkle DA. Outpatient perineal sling in adolescent boys with neurogenic incontinence. J Urol. 2009;182(4 Suppl):1792–6.
22. &#8226; Adams RC, Vachha B, Samuelson ML, Keefover-Hicks A, Snodgrass WT. Incidence of new onset metabolic acidosis following enteroplasty for myelomeningocele. J Urol. 2010 Jan;183(1):302–5. The authors matched patients with self- controls both before and after bladder augmentation and found no significant changes in electrolytes or development in metabolic acidosis postoperatively.
23. Kaye JD, Jafri SM, Cuda SP, Kalisvaart JF, Cerwinka WH, Kirsch AJ. Same setting laparoscopic antegrade continence enema and antegrade bladder neck injection for constipation and urinary incontinence in the spina bifida population. J Urol. 2010;184(4 Suppl):1644–50.
24. Dean GE, Kirsch AJ, Packer MG, Scherz HC, Zaontz MR. Antegrade and retrograde endoscopic dextranomer/hyaluronic Acid bladder neck bulking for pediatric incontinence. J Urol. 2007;178(2):652–5.
25. Tiryaki S, Ergun O, Celik A, Ulman I, Avanoglu A. Success of Malone’s antegrade continence enema (MACE) from the patients’ perspective. Eur J Pediatr Surg. 2010;20(6):405–7.