An evaluation of onobotulinumtoxinA as a therapeutic option for pediatric neurogenic detrusor overactivity.

INTRODUCTION: Neurogenic detrusor overactivity (NDO) results in involuntary detrusor contractions during bladder filling or storage risking transmission of pressure to the upper urinary tracts and/or significant incontinence. The goals of bladder management in children with NDO prioritize the preservation of renal function, prevention of UTIs, and optimizing quality of life. First-line measures include intermittent catheterization and anticholinergic medication. However, when conservative measures fail, surgical intervention may be indicated. Historically, the next step was major reconstructive surgery to create a low-pressure urinary reservoir. The introduction of intravesical botulinum neurotoxin A (BoNT/A) for use in children in 2002 offered a less invasive option for management. However, its exact role is still evolving. AREAS COVERED: This article summarizes the mechanism of action of BoNT/A for management of NDO and evaluates the current literature defining common practice and clinical efficacy in children with NDO. The findings of the recently completed phase III trial for intravesical onabotulinumtoxinA in children are discussed in detail. EXPERT OPINION: As the first BoNT/A approved for use in children with NDO, onabotulinumtoxinA appears to be a safe and less invasive alternative to major reconstructive surgery. However, data defining appropriate patient selection and its role as a long-term treatment option continue to develop.

Understanding factors influencing primary treatment with intradetrusor onabotulinumtoxinA versus augmentation cystoplasty in patients with spina bifida.

PURPOSE: Surgical interventions in the urologic management of children with neurogenic bladder secondary to spina bifida aim to preserve upper tract function, prevent urinary tract infections, and optimize quality of life. However, since the introduction of intravesical onabotulinumtoxinA (Botox) in the management of these patients, the indications for choosing Botox over augmentation cystoplasty (AC) remain undefined. The objective of this study was to determine which factors lead patients to undergo Botox versus AC as a primary surgical treatment after failing medical management. METHODS: We retrospectively reviewed the records of pediatric patients with myelomeningocele undergoing either primary Botox or primary AC at our institution between 2013 and 2018. We recorded demographic and clinical information. We identified 10 important clinical decision-making factors: bladder trabeculation, vesicoureteral reflux, or hydronephrosis on imaging; end-filling pressure (EFP) ≥40 cm H2O, detrusor overactivity, detrusor-sphincter dyssynergia, or reduced capacity on urodynamic studies; physician-perceived bladder hostility; and patient/family desire for continence and independence. The presence of these factors was compared between patients undergoing either primary Botox or primary AC. RESULTS: We identified 14 and 50 myelomeningocele patients who underwent primary AC and primary Botox, respectively. We found no significant differences in age, sex, race, or history of reconstructive surgery (antegrade continence enema or catheterizable channel). For the 10 decision-making factors, desire for independence/continence (p = <0.001) and reduced capacity (p = 0.002) were significantly associated with AC, while trabeculation (p = 0.006), EFP ≥40 cm H2O (p = 0.029), rising slope (p = 0.019), and physician-perceived hostility (p = 0.012) were significantly more common with Botox. CONCLUSIONS: At our institution, quality of life measures prompted AC over objective urodynamic or imaging findings before attempting Botox. These findings support a shared decision-making approach when considering surgical intervention for neurogenic bladder secondary to myelomeningocele.

Pelvic floor biofeedback therapy in children: Assessment of symptom scores in responders and non-responders.

INTRODUCTION: Pelvic Floor Biofeedback Therapy (PFBT) can be an effective treatment for pediatric lower urinary tract symptoms (LUTS). Due to differing perceptions of efficacy and practice patterns, we sought to further evaluate PFBT in our practice. We hypothesized that PFBT results in quiescence of EMG activity during voiding and improves questionnaire scores in patients with LUTS. METHODS: We retrospectively reviewed all patients undergoing PFBT and refined the analysis to females ≥6 years old with ≥2 sessions with completed voiding questionnaires pre- and post-treatment, active EMG during voiding, with non-neurogenic urinary tract complaints refractory to standard urotherapy. Validated Bladder Bowel Dysfunction (BBD) questionnaires were collected at each visit. Quiescence of EMG activity and changes in BBD score were the primary outcomes. RESULTS: 229 patients underwent ≥1 PFBT session, of which 64 females ≥6 years of age with ≥2 PFBT sessions and completed pre and post PFBT voiding questionnaires were identified. In this group, mean age at PFBT start was 10.1 (6.2-17.0). Patients completed 3.1 sessions (2-6). No difference was seen in post-void residual (PVR) between first and last session (23.8 vs 22.6 mL, P = 0.55). Median questionnaire score decreased from 18 (4-42) before to 13 (2-28) following PFBT (P < 0.0001). Responders, characterized by silencing of the EMG after PFBT, occurred in 31% (20/64). Non-responders were younger (P = 0.007) with higher pre-PFBT questionnaire scores. CONCLUSION: The use of PFBT appears to result in a significant reduction in symptom scores, though quiescence of EMG was observed following therapy in less than 1/3 of patients.

Prospective Evaluation of Sacral Neuromodulation in Children: Outcomes and Urodynamic Predictors of Success.

PURPOSE: Sacral neuromodulation has been demonstrated to improve refractory bowel bladder dysfunction in children. The purpose of the current study was to determine whether results are durable in children after longer followup, whether children with a lower body mass index are at risk for device failure and whether pretreatment urodynamic evaluation can predict posttreatment outcome. MATERIALS AND METHODS: Pediatric patients with refractory bowel bladder dysfunction were enrolled following informed consent and followed prospectively. All patients underwent preoperative videourodynamic evaluation and a 2-stage implantation procedure. Validated questionnaires were used to assess symptom severity and quality of life. Complications were analyzed with regard to treatment required and patient body mass index. RESULTS: During 45 months 30 patients were enrolled. Median age was 8.3 years at enrollment. Median followup was 14.8 months. Patients had significant improvement in quality of life and symptom scores, which persisted at the most recent followup. Patients who had uninhibited detrusor contractions on preoperative urodynamic assessment had significantly greater improvement in symptoms. Of the patients 23% had a complication requiring reoperation, most commonly neurostimulator lead breakage in those with a significantly lower body mass index. CONCLUSIONS: Sacral neuromodulation significantly improves quality of life and symptom severity in children with refractory bowel bladder dysfunction. Children gain greater benefit if they show uninhibited bladder contractions on preoperative urodynamic evaluation. Children have a high rate of lead breakage requiring operative revision, which was seen after minor trauma in those with a lower body mass index.

Outcomes of incontinent ileovesicostomy in the pediatric patient.

PURPOSE: Ileovesicostomy is a reconstructive option in complex urological cases but pediatric specific outcomes are lacking. We report our results with pediatric ileovesicostomy. MATERIALS AND METHODS: We retrospectively evaluated patients younger than 18 years undergoing incontinent ileovesicostomy at Vanderbilt University. History, urinary tract management and operative course were reviewed in the electronic medical record. Particular attention was given to immediate and long-term postoperative complications. RESULTS: Nine patients underwent incontinent ileovesicostomy between 2000 and 2013 at a mean age of 10.3 years (range 1.4 to 15.5). Surgical indication was sequelae of neurogenic or nonneurogenic neurogenic bladder (such as infection or worsening hydronephrosis) in 5 patients, reversal of vesicostomy in 3 and closure of cloacal exstrophy in 1. All 9 patients were thought incapable of reliable clean intermittent catheterization due to family unwillingness, poor social support or patient refusal. Median followup was 11.5 months (mean 48.2, range 1.3 to 144.8). Immediate postoperative complications included ileus requiring total parenteral nutrition and a wound infection in 1 patient. Long-term complications included urinary tract infection in 2 patients (febrile in 1 and positive culture for foul smelling urine in 1), stomal issues in 2 and temporary urethral leakage in 1. Constipation affected 3 children in long-term followup (all with neurogenic bowel preoperatively). Postoperative creatinine was stable or improved in all patients. CONCLUSIONS: Ileovesicostomy is a viable approach in children left with few other options, particularly those who are noncompliant or physically/socially unable to handle catheterization. This operation can help keep such patients out of diapers.

Prospective evaluation of sacral nerve modulation in children with validated questionnaires.

PURPOSE: Sacral neuromodulation for refractory urinary dysfunction in pediatrics shows promising results. We prospectively evaluated patients undergoing sacral neuromodulation using validated quality of life and bladder dysfunction questionnaires. MATERIALS AND METHODS: All patients were prospectively enrolled in the study. Two validated questionnaires were completed preoperatively, after lead placement and at all followups. The PedsQL™ 4.0 Generic Core Scale, which assesses quality of life and bladder dysfunction, was quantified using the Vancouver Nonneurogenic Lower Urinary Tract Dysfunction/Dysfunctional Elimination Syndrome (NLUTD/DES) questionnaire. The Wilcoxon matched pairs test was used for statistical analysis with p <0.05 considered significant. RESULTS: A total of 14 patients with a median age of 10 years were enrolled in the study. Median followup was 6 months. All patients underwent generator placement. No significant difference was seen in physical quality of life. Before and after lead placement mean ± SD psychosocial quality of life scores were 70.6 ± 17.4 and 81.43 ± 14.8 (p = 0.02), mean total quality of life scores were 75 ± 15.3 and 84.04 ± 13.2 (p = 0.006) and median NLUTD/DES scores were 23 ± 7.8 and 10.5 ± 7.0 (p <0.001), respectively. One month postoperatively a significant difference was seen in total quality of life and NLUTD/DES scores. Two patients required replacement of the temporary lead or generator. There were no infections. CONCLUSIONS: Patients undergoing sacral neuromodulation had significant improvement in NLUTD/DES scores, and psychosocial and overall total quality of life. Results were durable at 1 month. Continuing to follow these patients in a prospective manner with validated questionnaires will strengthen the current evidence supporting sacral neuromodulation in the pediatric population.

Factors that influence outcomes of the Mitrofanoff and Malone antegrade continence enema reconstructive procedures in children.

PURPOSE: Surgical techniques that provide adequate urinary and fecal continence in children with neurogenic bladder and bowel dysfunction are becoming increasingly used. We reviewed our experience and discuss factors that influence outcome. MATERIALS AND METHODS: Between 1994 and 2000, 65 stomal procedures were performed in 47 patients. For the urinary continent catheterizable channel we used appendix in 60% of cases, a continent bladder tube in 20%, a Yang-Monti tube in 16% and ureter in 4%. For the antegrade continence enema continent catheterizable channel we used appendix in 85% of cases, a Yang-Monti tube in 5% and a cecal tube in 10%. In the 19 patients who underwent simultaneous Mitrofanoff and antegrade continence enema procedures the urinary continent catheterizable channel was appendix in 21%, a Yang-Monti tube in 32% and continent vesicostomy in 47%. Patients were divided into 2 groups based on compliance status. In addition, percentile body weight for age was evaluated. RESULTS: Stomal continence was achieved in 63 of the 65 cases (97%). Of the patients who underwent the antegrade continence enema procedure 95% achieved continence via the rectum. Except for ureter stenosis rates according to continent catheterizable channel type did not differ greatly, namely 19% for appendix, 11% for the Yang-Monti tube, 22% for the bladder tube, 50% for ureter and 0% for the cecal tube. Infectious complications developed in 16 patients and 4 had stones. The rates of infection (p = 0.004), stomal stenosis (p = 0.001) and revision (p = 0.004) were statistically lower in the compliant group and the stone formation rate showed a trend favoring the compliant group (p = 0.11). No significant difference was noted for incontinence. Percentile weight predicted a higher rate of stomal stenosis with the highest rate of stomal stenosis overall in the greater than 100th percentile group. CONCLUSIONS: The Mitrofanoff and antegrade continence enema procedures are reliable and effective. Proper patient selection and surgical technique with a tension-free anastomosis are essential. The choice of tissue for constructing the continent catheterizable channel is not as important as patient compliance, age and possibly body habitus. This report reinforces the importance of careful screening, and rigorous preoperative and postoperative teaching to achieve overall patient success.