Evaluation, treatment & intervention in the pediatric neuropathic bladder Paul F. Austin, MD, FAAP Professor of Urologic Surgery Department of Surgery Division of Urologic Surgery St. Louis Children’s Hospital Washington University School of Medicine

Department of Surgery Division of Urologic Surgery ICCS Standardisation Documents

Department of Surgery Division of Urologic Surgery ICCS Standardisation Documents

Department of Surgery Division of Urologic Surgery Disclaimers and limitations Not a systematic literature review There is a paucity of level I or level II ‘‘levels of evidence’’ publications These recommendations are a consensus of a compilation of best practices Review of the literature Relevant research Expert opinion Current understanding on the pathophysiology of neuropathic bladder and bowel Draft review document was open to all the ICCS members via the ICCS web site Feedback was considered by the core authors and by agreement, amendments were made as necessary

Department of Surgery Division of Urologic Surgery Objectives Neuropathic bladder & bowel documents To create an educational reference document that will guide healthcare providers in the evaluation and management of children with neuropathic bladder & bowel dysfunction To provide a consensus view of the members of the ICCS in the evaluation and management of children with neuropathic bladder & bowel dysfunction

Department of Surgery Division of Urologic Surgery Initial evaluation Determined by several factors: Timing of presentation or diagnosis – infancy vs. older child Etiology

Department of Surgery Division of Urologic Surgery Open spinal cord lesion Initial evaluation Check PVR Ultrasound or catheter Urodynamics Usually 2 -3 months of age Screening for: High pressure DO contractions Elevated detrusor filling &/or voiding pressures

Department of Surgery Division of Urologic Surgery Open spinal cord lesion Initial evaluation Renal & bladder U/S Screening for: Hydronephrosis, Ureteral dilation

Department of Surgery Division of Urologic Surgery Open spinal cord lesion Initial evaluation Renal & bladder U/S Screening for: Discrepancy in renal size or contour RK: 9.2 cmLK: 6.7 cm

Department of Surgery Division of Urologic Surgery Open spinal cord lesion Initial evaluation Renal & bladder U/S Screening for: Bladder wall thickness

Department of Surgery Division of Urologic Surgery Open spinal cord lesion Initial evaluation VCUG Not routine Indicated when: Abnormal U/S imaging of kidneys Bladder urodynamic studies reveal high risk Detrusor overactivity Poor detrusor compliance Elevated leak point pressure and DSD

Department of Surgery Division of Urologic Surgery Neuropathic bladder – Video-urodynamics

Department of Surgery Division of Urologic Surgery Follow-up of NBD dysfunction Newborn to toddler Urodynamic studies High risk CIC +/- anticholinergics Low risk Diaper voiding Repeat UDS (with RBUS) in 2 – 3 months after initiating therapeutic interventions RBUS every 6 months for child with DO UDS yearly unless changes seen on RBUS or with lower extremities Rationale: Elevated risk of developing tethered cord

Department of Surgery Division of Urologic Surgery Follow-up of NBD dysfunction Toddler to adolescent Cord tethering risk lessens RBUS yearly or every 6 months UDS Changes on RBUS Changes in ambulation or lower extremity function Changes in continence Increased UTIs

Department of Surgery Division of Urologic Surgery Follow-up of NBD dysfunction Adolescent to adult 2 nd time period of growth spurt and increased risk of tethering RBUS yearly May consider every 2 years after growth velocity diminishes UDS Changes on RBUS Changes in ambulation or lower extremity function Changes in continence Increased UTIs

Department of Surgery Division of Urologic Surgery Follow-up of NBD dysfunction Adulthood RBUS every 3 years UDS Changes on RBUS Changes in continence Increased UTIs

Department of Surgery Division of Urologic Surgery Evaluation of neuropathic bowel dysfunction History Frequency of bowel movements Consistency of feces: Hard Soft Watery Current use of laxatives Frequency of fecal incontinence Child’s ability: To feel the urge to defecate To sit on the toilet To cooperate with bowel regimen or program Determine the child’s response to prior treatments Dietary measures Digital rectal stimulation Enemas Suppositories

Department of Surgery Division of Urologic Surgery Evaluation of neuropathic bowel dysfunction History 2-week bowel diary Validated assessment of a child’s defecation habits Although not mandatory, it is an excellent supplement to history taking

Department of Surgery Division of Urologic Surgery Treatment: Neuropathic bladder & bowel

Department of Surgery Division of Urologic Surgery Pharmacotherapy Anticholinergics Mainstay of drug therapy Level I evidence Target muscarinic receptors M2 & M3 Systemic implications M1-M5 Improve bladder wall compliance Diminish storage pressures Convert NGB from high to low risk Abolishes detrusor overactivity Provides time for CIC Provides urinary continence M3 M2 M1M4M2 ACh Anticholinergics

Department of Surgery Division of Urologic Surgery Pre-treatmentPost-treatment Anticholinergic effects Detrusor overactivity

Department of Surgery Division of Urologic Surgery Anticholinergic effects Detrusor compliance Pre-treatmentPost-treatment

Department of Surgery Division of Urologic Surgery Pharmacotherapy Botulinum-A-Toxin Inhibits ACh release at NMJ Botox may modulate both sensory & motor pathways Small, uncontrolled studies in children with NGB Improved clinical and urodynamic parameters: Improved continence Reduced max detrusor pressure Increased detrusor compliance Not approved by FDA or the EMEA for the treatment of NBD BTX-A use is off-label requiring informed consent FDA approval in adults 2011 Treatment of urinary incontinence due to DO associated with a neurologic condition in adults who have an inadequate response to or are intolerant of an anticholinergic medication Spinal cord injury Multiple sclerosis Adult Max dose = 200 U

Department of Surgery Division of Urologic Surgery Pharmacotherapy Antibiotics No level I evidence of medical benefit to using antibiotic prophylaxis in children with NBD who perform CIC. No difference in the rate of symptomatic or total UTIs Alters the normal skin and bladder flora Increased selection of virulent bacterial isolates Klebsiella and Pseudomonas Antibiotic prophylaxis – selective and individualized Focus on better emptying with CIC

Department of Surgery Division of Urologic Surgery Catheterization Non-latex catheters are employed exclusively Cochrane Review - incidence of UTI Lack of evidence that one catheter type, technique, or strategy is better Modification of catheters and catheter regimens should be made on an individual basis for children with NBD

Department of Surgery Division of Urologic Surgery Neuromodulation therapy Intravesical electrical stimulation Labor intensive & controversial Only one randomized, placebo-controlled trial No efficacy demonstrated in children with NBD

Department of Surgery Division of Urologic Surgery Neuromodulation therapy Sacral nerve stimulation Primarily been reported in the treatment of patients with non-neuropathic bladder Sacral nerve stimulation is considered investigational at this time

Department of Surgery Division of Urologic Surgery Neuromodulation therapy Biofeedback No significant studies of biofeedback have been reported in children with NBD

Department of Surgery Division of Urologic Surgery Surgical intervention Patients who fail medical management Goals: Attaining safe bladder storage pressures & capacity Increasing bladder outlet resistance

Department of Surgery Division of Urologic Surgery Attaining safe bladder storage pressures & capacity Urethral dilation Mixed efficacy Selected patients Technically easiest in females Vesicostomy Excellent temporizing procedure Ideal in infants and toddlers

Department of Surgery Division of Urologic Surgery Bladder augmentation Achieves complete continence in children with neuropathic bladder Allows independence & self-esteem Requires patient commitment & compliance

Department of Surgery Division of Urologic Surgery Bladder augmentation Definitive method of creating a safe, low-pressure storage Small bowel Most commonly employed Large bowel Ureter Auto-augmentation

Department of Surgery Division of Urologic Surgery Bladder augmentation Associated complications Acid-Base imbalances UTIs Stones Bladder augment perforation Cancer risk

Department of Surgery Division of Urologic Surgery Increasing bladder outlet resistance Variety of surgical approaches Fascial sling Artificial urinary sphincter Bladder neck reconstruction Bladder neck closure Pump Cuf f Reservoir

Department of Surgery Division of Urologic Surgery Treatment Neuropathic bowel High fiber diet Digital stimulation / glycerin suppositories Laxatives Transanal irrigation – e.g. cone enema Colonic irrigation ACE or MACE Chait tube / Cecostomy tube

Department of Surgery Division of Urologic Surgery Summary Neuropathic bladder & bowel documents Provide a guideline for appropriate evaluation and timely surveillance of the various neuro-urologic conditions that affect children Underscore the variability and complexity of patients with NBD & bowel Non-surgical intervention is promoted before undertaking major surgery CIC +/- anticholinergics are mainstay interventions Dietary fiber, laxatives and enemas are common in bowel management Surgical intervention After failure of medical therapy Requires patient commitment and compliance

Department of Surgery Division of Urologic Surgery Surgical reconstruction Neuropathic bladder & bowel

Department of Surgery Division of Urologic Surgery Bowel segments

Department of Surgery Division of Urologic Surgery Bowel segments

Department of Surgery Division of Urologic Surgery Mitrofanoff principal *

Department of Surgery Division of Urologic Surgery

Department of Surgery Division of Urologic Surgery Surgical reconstruction Neurogenic bladder & bowel

Department of Surgery Division of Urologic Surgery Bowel segments Preparation

Department of Surgery Division of Urologic Surgery Monti Catheterizable channel

Department of Surgery Division of Urologic Surgery Bowel segments

Department of Surgery Division of Urologic Surgery Catheterizable channels & augmentation

Department of Surgery Division of Urologic Surgery Continence mechanism How does it work?

Department of Surgery Division of Urologic Surgery MACE Malone Antegrade Continence Enema

Department of Surgery Division of Urologic Surgery Refractory constipation Neuropathic bladder & bowel Myelodysplasia Anorectal malformations

Department of Surgery Division of Urologic Surgery Patient selection Refractory constipation Failed all “conservative measures” Underlying pathology Chronic idiopathic constipation = poorly Neuropathic bowel & anorectal malformations = good Age > 5 yo = good results Compliance & Motivation

Department of Surgery Division of Urologic Surgery Continence mechanism MACE

Department of Surgery Division of Urologic Surgery Appendiceal mesentery MACE

Department of Surgery Division of Urologic Surgery Mesenteric windows Dissection

Department of Surgery Division of Urologic Surgery Mesenteric windows MACE

Department of Surgery Division of Urologic Surgery Pre-cecal wrap MACE

Department of Surgery Division of Urologic Surgery Cecal wrap MACE

Department of Surgery Division of Urologic Surgery MACE Cecal wrap

Department of Surgery Division of Urologic Surgery Mitrofanoff & MACE (Appendix)

Department of Surgery Division of Urologic Surgery Mitrofanoff & MACE (Appendix)

Department of Surgery Division of Urologic Surgery Spiral Monti Casale, J Urol, 162:1743, 1999

Department of Surgery Division of Urologic Surgery Spiral Monti

Department of Surgery Division of Urologic Surgery Spiral Monti

Department of Surgery Division of Urologic Surgery Spiral Monti

Department of Surgery Division of Urologic Surgery MACE alternatives Appendectomy

Department of Surgery Division of Urologic Surgery Colon tube

Department of Surgery Division of Urologic Surgery

Department of Surgery Division of Urologic Surgery

Department of Surgery Division of Urologic Surgery

Department of Surgery Division of Urologic Surgery

Department of Surgery Division of Urologic Surgery

Department of Surgery Division of Urologic Surgery Appendiceal pedicle Limitations

Department of Surgery Division of Urologic Surgery Stoma construction V-flap

Department of Surgery Division of Urologic Surgery Stomas MACE & Mitrofanoff

Department of Surgery Division of Urologic Surgery Thank you!