Skip to main content

Advertisement

SpringerLink
Log in

Botulinum Toxin A’s Expanding Role in the Management of Pediatric Lower Urinary Tract Dysfunction

  • Pediatric Urology (M Castellan and R Gosalbez, Section Editors)
  • Published:
Current Urology Reports Aims and scope Submit manuscript

Abstract

Botulinum toxin A’s (Onabotulinum toxin A – OnabotA) utility in the pediatric population is evolving, and is currently being used in the treatment of lower urinary tract dysfunction, both in children with neuropathic compromise, and non-neuropathic overactive bladders. The results of having OnabotA injected directly into the bladder wall cystoscopically are: a more compliant bladder with reduced bladder pressure, avoiding renal compromise and upper urinary tract deterioration; increased bladder capacity; and the ability for children to reach an improved degree of urinary continence through a minimally invasive approach. A growing body of research in patients with either neuropathic bladders or overactive bladders (OAB), have shown excellent results when looking at urodynamic parameters, patient satisfaction and improvement in symptomatology. One of the main indications for the use of OnabotA in children with neuropathic bladders is to delay or avoid the need for augmentation cystoplasty. By achieving the aforementioned results, some children can delay or avoid this more invasive and permanent procedure. Prospective studies are needed to answer questions regarding optimal dosage and frequency, ideal patient selection criteria and assessment of long-term outcomes and complications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

ACT:

Anticholinergic therapy

OnabotA:

Onabotulinum toxin A

CIC:

Clean intermittent catheterization

OAB:

Overactive bladder

IC:

Interstitial cystitis

SP:

Substance P

DLPP:

Detrusor leak point pressure

LD50:

Lethal dose in 50 % of subjects

IDI:

Intra-detrusor injection(s)

UDS:

Urodynamic study(ies)

Ab:

Antibody

RTX:

Resiniferatoxin

DESD:

Detrusor external sphincter dyssynergia

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Altaweel W, Jednack R, Bilodeau C, Corcos J. Repeated intradetrusor botulinum toxin type A in children with neurogenic bladder due to myelomeningocele. J Urol. 2006;175(3 Pt 1):1102–5. doi:10.1016/S0022-5347(05)00400-3.

    Article  CAS  PubMed  Google Scholar 

  2. Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford AP, Davis JB, et al. Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol. 2005;174(3):977–82. doi:10.1097/01.ju.0000169481.42259.54. discussion 982-973.

    Article  CAS  PubMed  Google Scholar 

  3. Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, et al. Botulinum toxin as a biological weapon: medical and public health management. [Consensus Development Conference Research Support, Non-U.S. Gov't Review]. JAMA. 2001;285(8):1059–70.

    Article  CAS  PubMed  Google Scholar 

  4. Baldwin CM, Keating GM. Transdermal oxybutynin. [Review]. Drugs. 2009;69(3):327–37. doi:10.2165/00003495-200969030-00008.

    Article  CAS  PubMed  Google Scholar 

  5. Dressler D. Clinical features of antibody-induced complete secondary failure of botulinum toxin therapy. [Research Support, Non-U.S. Gov't]. Eur Neurol. 2002;48(1):26–9.

    Article  CAS  PubMed  Google Scholar 

  6. Ferrara P, D'Aleo CM, Tarquini E, Salvatore S, Salvaggio E. Side-effects of oral or intravesical oxybutynin chloride in children with spina bifida. BJU Int. 2001;87(7):674–8.

    Article  CAS  PubMed  Google Scholar 

  7. Foran PG, Mohammed N, Lisk GO, Nagwaney S, Lawrence GW, Johnson E, et al. Evaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared with the long lasting type A. Basis for distinct durations of inhibition of exocytosis in central neurons. [Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.]. J Biol Chem. 2003;278(2):1363–71. doi:10.1074/jbc.M209821200.

    Article  CAS  PubMed  Google Scholar 

  8. Guerra LA, Moher D, Sampson M, Barrowman N, Pike J, Leonard M. Intravesical oxybutynin for children with poorly compliant neurogenic bladder: a systematic review. [Review]. J Urol. 2008;180(3):1091–7. doi:10.1016/j.juro.2008.05.056.

    Article  CAS  PubMed  Google Scholar 

  9. Hoebeke P, De Caestecker K, Vande Walle J, Dehoorne J, Raes A, Verleyen P, et al. The effect of botulinum-A toxin in incontinent children with therapy resistant overactive detrusor. [Clinical Trial]. J Urol. 2006;176(1):328–30. doi:10.1016/S0022-5347(06)00301-6. discussion 330-321.

    Article  CAS  PubMed  Google Scholar 

  10. Holds JB, Alderson K, Fogg SG, Anderson RL. Motor nerve sprouting in human orbicularis muscle after botulinum A injection. [Research Support, Non-U.S. Gov't]. Invest Ophthalmol Vis Sci. 1990;31(5):964–7.

    CAS  PubMed  Google Scholar 

  11. 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. doi:10.1016/j.urology.2010.09.036.

    Article  PubMed  Google Scholar 

  12. Kajbafzadeh AM, Moosavi S, Tajik P, Arshadi H, Payabvash S, Salmasi AH, et al. Intravesical injection of botulinum toxin type A: management of neuropathic bladder and bowel dysfunction in children with myelomeningocele. [Clinical Trial]. Urology. 2006;68(5):1091–6. doi:10.1016/j.urology.2006.05.056. discussion 1096-1097.

    Article  PubMed  Google Scholar 

  13. Kajbafzadeh AM, Nikfarjam L, Mahboubi AH, Dianat S. Antibody formation following botulinum toxin type A (Dysport) injection in children with intractable bladder hyper-reflexia. Urology. 2010;76(1):233–7. doi:10.1016/j.urology.2010.03.023. This study showed that repeated injections of OnabotA did not stimulate antibody formation. This is important because we now have an idea of the possible long-term effects of frequent OnabotA injections.

    Article  PubMed  Google Scholar 

  14. Karsenty G, Elzayat E, Delapparent T, St-Denis B, Lemieux MC, Corcos J. Botulinum toxin type a injections into the trigone to treat idiopathic overactive bladder do not induce vesicoureteral reflux. [Clinical Trial]. J Urol. 2007;177(3):1011–4. doi:10.1016/j.juro.2006.10.047.

    Article  PubMed  Google Scholar 

  15. Kask M, Rintala R, Taskinen S. Effect of onabotulinumtoxinA treatment on symptoms and urodynamic findings in pediatric neurogenic bladder. J Pediatr Urol. 2013. doi:10.1016/j.jpurol.2013.09.004.

    PubMed  Google Scholar 

  16. Krause P, Fuhr U, Schnitker J, Albrecht U, Stein R, Rubenwolf P. Pharmacokinetics of intravesical versus oral oxybutynin in healthy adults: results of an open label, randomized, prospective clinical study. [Comparative Study Randomized Controlled Trial]. J Urol. 2013;190(5):1791–7. doi:10.1016/j.juro.2013.05.011. This is a study that showed that intravesical administration of oxybutynin is an alternative to oral oxybutynin in patients who cannot tolerate adverse effects of the oral preparation. It is also important because it can also be used as an alternative to OnabotA injections in children.

    Article  CAS  PubMed  Google Scholar 

  17. Manecksha RP, Cullen IM, Ahmad S, McNeill G, Flynn R, McDermott TE, et al. Prospective randomised controlled trial comparing trigone-sparing versus trigone-including intradetrusor injection of abobotulinumtoxinA for refractory idiopathic detrusor overactivity. [Randomized Controlled Trial]. Eur Urol. 2012;61(5):928–35.

    Article  CAS  PubMed  Google Scholar 

  18. Mokhless I, Gaafar S, Fouda K, Shafik M, Assem A. Botulinum A toxin urethral sphincter injection in children with nonneurogenic neurogenic bladder. J Urol. 2006;176(4 Pt 2):1767–70. doi:10.1016/j.juro.2006.03.119. discussion 1770.

    Article  CAS  PubMed  Google Scholar 

  19. Painter KA, Vates TS, Bukowski TP, Fleming P, Freedman AL, Smith CA, et al. Long-term intravesical oxybutynin chloride therapy in children with myelodysplasia. J Urol. 1996;156(4):1459–62.

    Article  CAS  PubMed  Google Scholar 

  20. Pang X, Marchand J, Sant GR, Kream RM, Theoharides TC. Increased number of substance P positive nerve fibres in interstitial cystitis. [Research Support, U.S. Gov't, P.H.S.]. Br J Urol. 1995;75(6):744–50.

    Article  CAS  PubMed  Google Scholar 

  21. Payne CK, Mosbaugh PG, Forrest JB, Evans RJ, Whitmore KE, Antoci JP, et al. Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. [Clinical Trial Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't]. J Urol. 2005;173(5):1590–4. doi:10.1097/01.ju.0000154631.92150.ef.

    Article  CAS  PubMed  Google Scholar 

  22. Petronijevic V, Lazovic M, Vlajkovic M, Slavkovic A, Golubovic E, Miljkovic P. Botulinum toxin type A in combination with standard urotherapy for children with dysfunctional voiding. [Clinical Trial]. J Urol. 2007;178(6):2599–602. doi:10.1016/j.juro.2007.08.027. discussion 2602-2593. This study used a maximum dose of 500 units of OnabotA in pediatric patients. This is the highest dose ever experimented on in pediatric urology patients, and was shown to be safe.

  23. Radojicic ZI, Perovic SV, Milic NM. Is it reasonable to treat refractory voiding dysfunction in children with botulinum-A toxin? J Urol. 2006;176(1):332–6. doi:10.1016/S0022-5347(06)00298-9. discussion 336.

    Article  PubMed  Google Scholar 

  24. Riccabona M, Koen M, Schindler M, Goedele B, Pycha A, Lusuardi L, et al. Botulinum-A toxin injection into the detrusor: a safe alternative in the treatment of children with myelomeningocele with detrusor hyperreflexia. [Comparative Study]. J Urol. 2004;171(2 Pt 1):845–8. doi:10.1097/01.ju.0000108892.35041.2d. discussion 848.

    Article  CAS  PubMed  Google Scholar 

  25. Sanchez Freire V, Burkhard FC, Kessler TM, Kuhn A, Draeger A, Monastyrskaya K. MicroRNAs may mediate the down-regulation of neurokinin-1 receptor in chronic bladder pain syndrome. [Research Support, Non-U.S. Gov't]. Am J Pathol. 2010;176(1):288–303. doi:10.2353/ajpath.2010.090552.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Schulte-Baukloh H, Michael T, Schobert J, Stolze T, Knispel HH. Efficacy of botulinum-a toxin in children with detrusor hyperreflexia due to myelomeningocele: preliminary results. [Clinical Trial]. Urology. 2002;59(3):325–7. discussion 327–28. First and landmark study to report the effects of OnabotA in children with neuropathic bladders.

  27. Schulte-Baukloh H, Michael T, Sturzebecher B, Knispel HH. Botulinum-a toxin detrusor injection as a novel approach in the treatment of bladder spasticity in children with neurogenic bladder. Eur Urol. 2003;44(1):139–43.

    Article  CAS  PubMed  Google Scholar 

  28. Schulte-Baukloh H, Priefert J, Knispel HH, Lawrence GW, Miller K, Neuhaus J. Botulinum toxin A detrusor injections reduce postsynaptic muscular M2, M3, P2X2, and P2X3 receptors in children and adolescents who have neurogenic detrusor overactivity: a single-blind study. [Comparative Study Randomized Controlled Trial]. Urology. 2013;81(5):1052–7. doi:10.1016/j.urology.2012.12.021.

    Article  PubMed  Google Scholar 

  29. Schurch B, Stohrer M, Kramer G, Schmid DM, Gaul G, Hauri D. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. [Research Support, Non-U.S. Gov't]. J Urol. 2000;164(3 Pt 1):692–7.

    Article  CAS  PubMed  Google Scholar 

  30. Scott AB, Suzuki D. Systemic toxicity of botulinum toxin by intramuscular injection in the monkey. [Research Support, U.S. Gov't, P.H.S.]. Mov Disord. 1988;3(4):333–5. doi:10.1002/mds.870030409.

    Article  CAS  PubMed  Google Scholar 

  31. Shaban AM, Drake MJ. Botulinum toxin treatment for overactive bladder: risk of urinary retention. [Review]. Curr Urol Rep. 2008;9(6):445–51.

    Article  PubMed  Google Scholar 

  32. Shaw GL, Patel HR. Transdermal oxybutynin: a review. [Review]. Expert Opin Drug Metab Toxicol. 2007;3(3):435–9. doi:10.1517/17425255.3.3.435.

    Article  CAS  PubMed  Google Scholar 

  33. 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. doi:10.1016/j.juro.2010.02.029.

    Article  PubMed  Google Scholar 

  34. Sobel J. Botulism. [Review]. Clin Infect Dis. 2005;41(8):1167–73. doi:10.1086/444507.

    Article  CAS  PubMed  Google Scholar 

  35. Szallasi A, Blumberg PM. Resiniferatoxin and its analogs provide novel insights into the pharmacology of the vanilloid (capsaicin) receptor. [Review]. Life Sci. 1990;47(16):1399–408.

    Article  CAS  PubMed  Google Scholar 

  36. Wyndaele JJ, Van Dromme SA. Muscular weakness as side effect of botulinum toxin injection for neurogenic detrusor overactivity. [Case Reports]. Spinal Cord. 2002;40(11):599–600. doi:10.1038/sj.sc.3101318.

    Article  CAS  PubMed  Google Scholar 

  37. Yarker YE, Goa KL, Fitton A. Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability. [Comparative Study Review]. Drugs Aging. 1995;6(3):243–62.

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Dr. Tarek Hassouna and Dr. Joseph M. Gleason each declare no potential conflicts of interest.

Dr. Armando J. Lorenzo is a consultant for and has received travel/accommodations expenses covered or reimbursed by Allergan.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Division of Paediatric Urology, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Tarek Hassouna, Joseph M. Gleason & Armando J. Lorenzo

  2. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Armando J. Lorenzo

Authors
  1. Tarek Hassouna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph M. Gleason
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Armando J. Lorenzo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Armando J. Lorenzo.

Additional information

This article is part of the Topical Collection on Pediatric Urology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hassouna, T., Gleason, J.M. & Lorenzo, A.J. Botulinum Toxin A’s Expanding Role in the Management of Pediatric Lower Urinary Tract Dysfunction. Curr Urol Rep 15, 426 (2014). https://doi.org/10.1007/s11934-014-0426-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11934-014-0426-1

Keywords

Search

Navigation