title: Breaking the vicious circle: Onabotulinum toxin A in children with therapy-refractory dysfunctional voiding.
abstract: BACKGROUND
  An increased activity of the external urethral sphincter or pelvic floor muscles during voluntary voiding leads to dysfunctional voiding. Frequently reported symptoms are urinary incontinence, urinary tract infections and high post-void residuals. Dysfunctional voiding is a common problem in school-aged children and despite various treatment options, 10-40% of the children remain therapy-refractory.
  
  
  OBJECTIVE
  The aim of this study is to evaluate the effectiveness of Onabotulinum toxin-A (BTX-A) injections in the external urethral sphincter in children with therapy-refractory dysfunctional voiding.
  
  
  METHODS
  Patients with therapy-refractory dysfunctional voiding who have received BTX-A injections in the external urethral sphincter from 2010 to 2013 were analysed. Children with known neuropsychiatric disorders were excluded. All children had abnormal flow patterns and increased pelvic floor tone during uroflowmetry/EMG studies. They had received at least five sessions of urotherapy and two sessions of pelvic floor physical therapy prior to treatment. A total of 100 IU of BTX-A was injected in the external urethral sphincter at the 3, 9 and 12 o'clock positions. Our main outcome measures were urinary incontinence, recurrent urinary tract infections and post-void residual.
  
  
  RESULTS
  A total of twenty patients, of whom 16 girls, with a median age of 9 years (range 5-14) were treated with BTX-A. The median follow-up was 13 months (range 5-34). Post-void residual decreased by 75% after BTX-A, from a median of 47.5 ml (16.3-88.5 ml) to 0 ml (0.0-28.0 ml) (p = 0.001) Six patients had a post-void residual < 20 ml prior to treatment. After BTX-A sixteen patients had a post-void residual <20 ml (Figure). No significant changes in uroflowmetry results was seen. Sixteen children are no longer daily incontinent, of whom 9 became completely dry (p = 0.0001). Eleven patients suffered from recurrent urinary tract infections prior to treatment. After BTX-A five children remained infection free, while the other six experienced only one urinary tract infection during follow-up (p = 0.003). Fourteen patients received additional urotherapy after BTX-A. Repeat injections were necessary in four patients after initial satisfactory results, with repeated good clinical responses. Two children showed no improvement after first BTX-A injection. No serious adverse events were reported.
  
  
  CONCLUSIONS
  The results in this homogenous group of patients confirm the conclusions of previous studies in opting BTX-A in the external urethral sphincter to be a viable treatment option for the therapy-refractory group of patients with dysfunctional voiding. What is new, is that in most of our patients post-injection urotherapy was used to amplify the BTX-A effect. During our long-term follow-up the satisfactory results were sustained, similar to the results of the long-term follow-up presented by Vricella et al. [1]. The retrospective character and relative small sample size are limitations of this study.
  
  
  CONCLUSIONS
  This study shows safe and persistent satisfactory results during our average 13-month follow-up in 90% of our patients with therapy-refractory dysfunctional voiding. A prospective study using validated and standardized measurements will be performed to affirm our results and evaluate the exact role of post-injection urotherapy.
authors: Department of Pediatric Urology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: l.thoen@erasmusmc.nl.
authors: L A
authors: LA
authors: 't Hoen
authors: Department of Pediatric Urology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: j.vandenhoek@erasmusmc.nl.
authors: J
authors: J
authors: van den Hoek
authors: Department of Pediatric Urology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: k.wolffenbuttel@erasmusmc.nl.
authors: K P
authors: KP
authors: Wolffenbuttel
authors: Department of Pediatric Urology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: f.vandertoorn.1@erasmusmc.nl.
authors: F
authors: F
authors: van der Toorn
authors: Department of Pediatric Urology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: j.scheepe@erasmusmc.nl.
authors: J R
authors: JR
authors: Scheepe
mesh_terms: D065087:Acetylcholine Release Inhibitors / Q000627:therapeutic use*; D000293:Adolescent; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D016896:Treatment Outcome; D014521:Urethra; D014555:Urination Disorders / Q000188:drug therapy*
chemical_list: D065087:Acetylcholine Release Inhibitors; D019274:Botulinum Toxins, Type A
keywords: Botulinum toxin type A; Dysfunctional voiding; Paediatrics; Therapy-refractory