Skip to main content
SpringerLink
Log in

Pharmacologic Management of Neurogenic Lower Urinary Tract Dysfunction

  • Chapter
  • First Online:
Book cover Neuro-Urology

  • 832 Accesses

Abstract

Lower urinary tract function requires complex and coordinated signaling between central and peripheral nervous systems. In patients with neurologic lesions, the development of neurogenic lower urinary tract dysfunction (NLUTD) can include neurogenic detrusor overactivity (NDO), detrusor areflexia, detrusor sphincter dyssynergia (DSD), or sphincter underactivity depending on the locations and extent of the lesion. The pharmacologic management of NLUTD is reviewed in this chapter following a brief summary of neurologic control of micturition and assessment of NLUTD. Antimuscarinics with or without intermittent catheterization are the first-line management of NDO, but mirabegron is a newer agent that has also shown efficacy in this population. Botulinum toxin A (BTX-A) injections into the detrusor muscle can be considered if medical therapy fails. Medical therapy for DSD has not been demonstrated as efficacious, but intrasphincteric BTX-A can be considered as an alternative to sphincterotomy. No medical therapy has been shown effective for the management of detrusor areflexia or sphincter underactivity. Lifelong follow-up is necessary to prevent the development of secondary complications, such as renal failure.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mansfield KJ, Liu L, Mitchelson FJ, et al. Muscarinic receptor subtypes in human bladder detrusor and mucosa, studied by radioligand binding and quantitative competitive RT-PCR: changes in ageing. Br J Pharmacol. 2005;144:1089–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. de Groat WC, Griffiths D, Yoshimura N. Neural control of the lower urinary tract. Compr Physiol. 2015;5:327–96.

    PubMed  PubMed Central  Google Scholar 

  3. Andersson K-E, Arner A. Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev. 2004;84:935–86. https://doi.org/10.1152/physrev.00038.2003.

    Article  PubMed  CAS  Google Scholar 

  4. Yoshimura N, Chancellor MB. Neurophysiology of lower urinary tract function and dysfunction. Rev Urol. 2003;5:S3–S10.

    PubMed  PubMed Central  Google Scholar 

  5. Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci. 2008;9:453–66. https://doi.org/10.1038/nrn2401.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Thor KB, Donatucci C. Central nervous system control of the lower urinary tract: new pharmacological approaches to stress urinary incontinence in women. J Urol. 2004;172:27–33. https://doi.org/10.1097/01.ju.0000118381.04432.22.

    Article  PubMed  CAS  Google Scholar 

  7. McCloskey KD. Interstitial cells of cajal in the urinary tract. In: Andersson K-E, Michel MC, editors. Urinary tract. Berlin: Springer; 2011. p. 233–54.

    Chapter  Google Scholar 

  8. Juszczak K, Maciukiewicz P, Drewa T, Thor P. Cajal–like interstitial cells as a novel target in detrusor overactivity treatment: true or myth? Cent Eur J Urol. 2013;66:1–5. https://doi.org/10.5173/ceju.2013.04.art5.

    Article  CAS  Google Scholar 

  9. Chai TC, Birder LA. Physiology and pharmacology of the bladder and urethra. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, editors. Campbell-Walsh urology, 11th ed. 2016. p. 1631–84.

    Google Scholar 

  10. Pakzad M, Ikeda Y, McCarthy C, et al. Contractile effects and receptor analysis of adenosine-receptors in human detrusor muscle from stable and neuropathic bladders. Naunyn Schmiedeberg’s Arch Pharmacol. 2016;389:921–9. https://doi.org/10.1007/s00210-016-1255-1.

    Article  CAS  Google Scholar 

  11. Jean-Xavier C, Sharples SA, Mayr KA, et al. Retracing your footsteps: developmental insights to spinal network plasticity following injury. J Neurophysiol. 2017. https://doi.org/10.1152/jn.00575.2017.

  12. McGuire EJ, Woodside JR, Borden TA, Weiss RM. Prognostic value of urodynamic testing in myelodysplastic patients. J Urol. 1981;126:205–9.

    Article  CAS  PubMed  Google Scholar 

  13. Weld KJ, Graney MJ, Dmochowski RR. Difference in bladder compliance with time and associations of bladder management with compliance in spinal cord injured patients. J Urol. 2000;163:1228–33.

    Article  CAS  PubMed  Google Scholar 

  14. Tarcan T, Sekerci CA, Akbal C, et al. Is 40 cm H2O detrusor leak point pressure cut-off reliable for upper urinary tract protection in children with myelodysplasia? Neurourol Urodyn. 2016;36:759–63. https://doi.org/10.1002/nau.23017.

    Article  PubMed  Google Scholar 

  15. Weld KJ, Graney MJ, Dmochowski RR. Clinical significance of detrusor sphincter dyssynergic type in patients with post-traumatic spinal cord injury. Urology. 2000;56:565–8.

    Article  CAS  PubMed  Google Scholar 

  16. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn. 2002;21:167–78. https://doi.org/10.1002/nau.10052.

    Article  PubMed  Google Scholar 

  17. Wein AJ. Classification of neurogenic voiding dysfunction. J Urol. 2081;125:605–9.

    Article  Google Scholar 

  18. Agrawal S, Agrawal RR, Wood HM. Establishing a multidisciplinary approach to the management of neurologic disease affecting the urinary tract. Urol Clin North Am. 2017;44:377–89. https://doi.org/10.1016/j.ucl.2017.04.005.

    Article  PubMed  Google Scholar 

  19. Feneley RCL, Hopley IB, Wells PNT. Urinary catheters: history, current status, adverse events and research agenda. J Med Eng Technol. 2015;39:459–70. https://doi.org/10.3109/03091902.2015.1085600.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Lapides J, Diokno AC, Silber SJ, Lowe BS. Clean, intermittent self-catheterization in the treatment of urinary tract disease. J Urol. 1972;107:458–61.

    Article  CAS  PubMed  Google Scholar 

  21. Chen TYH, Ponsot Y, Carmel M, et al. Multi-Centre study of Intraurethral valve-pump catheter in women with a hypocontractile or acontractile bladder. Eur Urol. 2005;48:628–33. https://doi.org/10.1016/j.eururo.2005.04.020.

    Article  PubMed  Google Scholar 

  22. Finkbeiner AE. Is bethanechol chloride clinically effective in promoting bladder emptying? A literature review. J Urol. 1985;134:443–9.

    Article  CAS  PubMed  Google Scholar 

  23. Riedl CR, Stephen RL, Daha LK, et al. Electromotive administration of intravesical bethanechol and the clinical impact on acontractile detrusor management: introduction of a new test. J Urol. 2000;164:2108–11.

    Article  CAS  PubMed  Google Scholar 

  24. Hindley RG, Brierly RD, Thomas PJ. Prostaglandin E2 and bethanechol in combination for treating detrusor underactivity. BJU Int. 2004;93(1):89–92. https://doi.org/10.1046/j.1464-410X.2004.04563.x.

    Article  PubMed  CAS  Google Scholar 

  25. Madhuvrata P, Singh M, Hasafa Z, Abdel-Fattah M. Anticholinergic drugs for adult neurogenic detrusor overactivity: a systematic review and meta-analysis. Eur Urol. 2012;62:816–30. https://doi.org/10.1016/j.eururo.2012.02.036.

    Article  PubMed  CAS  Google Scholar 

  26. Madersbacher H, Murtz G, Stohrer M. Neurogenic detrusor overactivity in adults: a review on efficacy, tolerability and safety of oral antimuscarinics. Spinal Cord. 2013;51:432–41. https://doi.org/10.1038/sc.2013.19.

    Article  PubMed  CAS  Google Scholar 

  27. Andersson K-E, Wein AJ. Pharmacologic management of lower urinary tract storage and emptying failure. In: Campbell-Walsh urology. 11th ed. Philadelphia: Elsevier; 2016. p. 1836–1874.e23.

    Google Scholar 

  28. Davila GW, Daugherty CA, Sanders SW. A short-term, multicenter, randomized double-blind dose titration study of efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J Urol. 2001;166:140–5.

    Article  CAS  PubMed  Google Scholar 

  29. Kennelly MJ, Lemack GE, Foote JE, Trop CS. Efficacy and safety of oxybutynin transdermal system in spinal cord injury patients with neurogenic detrusor overactivity and incontinence: an open-label, dose-titration study. Urology. 2009;74:741–5. https://doi.org/10.1016/j.urology.2009.05.008.

    Article  PubMed  Google Scholar 

  30. Krause P, Fuhr U, Schnitker J, et al. Pharmacokinetics of intravesical versus oral oxybutynin in healthy adults: results of an open label, randomized, prospective clinical study. J Urol. 2013;190:1791–7. https://doi.org/10.1016/j.juro.2013.05.011.

    Article  PubMed  CAS  Google Scholar 

  31. Schröder A, Albrecht U, Schnitker J, et al. Efficacy, safety, and tolerability of intravesically administered 0.1% oxybutynin hydrochloride solution in adult patients with neurogenic bladder: a randomized, prospective, controlled multi-center trial. Neurourol Urodyn. 2015;35:582–8. https://doi.org/10.1002/nau.22755.

    Article  PubMed  CAS  Google Scholar 

  32. De Wachter S, Wyndaele J. Intravesical oxybutynin: a local anesthetic effect on bladder C afferents. J Urol. 2003;169:1892–5. https://doi.org/10.1097/01.ju.0000049903.60057.4b.

    Article  PubMed  CAS  Google Scholar 

  33. van Kerrebroeck PEVA, Amarenco G, Thuroff JW, et al. Dose-ranging study of tolterodine in patients with detrusor hyperreflexia. Neurourol Urodyn. 1998;17:499–512.

    Article  PubMed  Google Scholar 

  34. Ethans KD, Nance PW, Bard RJ, et al. Efficacy and safety of tolterodine in people with neurogenic detrusor overactivity. J Spinal Cord Med. 2004;27:214–8.

    Article  PubMed  Google Scholar 

  35. Watanabe M, Yamanishi T, Honda M, et al. Efficacy of extended-release tolterodine for the treatment of neurogenic detrusor overactivity and/or low-compliance bladder. Int J Urol. 2010;17:931–6. https://doi.org/10.1111/j.1442-2042.2010.02635.x.

    Article  PubMed  CAS  Google Scholar 

  36. Madhuvrata P, Cody JD, Ellis G, Herbison GP, Hay-Smith J. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database Syst Rev. 2012;1:CD005429. https://doi.org/10.1002/14651858.CD005429.

    Article  PubMed  Google Scholar 

  37. Nilvebrant L, Andersson KE, Gilberg PG, et al. Tolterodine—a new bladder-selective antimuscarinic agent. Eur J Pharmacol. 1997;327:195–207.

    Article  CAS  PubMed  Google Scholar 

  38. Bycroft J, Leaker B, Wood S, et al. The effect of darifenacin on neurogenic detrusor overactivity in patients with spinal cord injury. International Continence Society. 2003.

    Google Scholar 

  39. Carl S, Laschke S. Darifenacin is also effective in neurogenic bladder dysfunction (multiple sclerosis). Urology. 2006;68(Suppl):250–1. https://doi.org/10.1016/j.urology.2006.08.736.

    Article  Google Scholar 

  40. Amarenco G, Sutory M, Zachoval R, et al. Solifenacin is effective and well tolerated in patients with neurogenic detrusor overactivity: results from the double-blind, randomized, active- and placebo-controlled SONIC urodynamic study. Neurourol Urodyn. 2017;36(2):414–21. https://doi.org/10.1002/nau.22945.

    Article  CAS  PubMed  Google Scholar 

  41. Stohrer M, Bauer P, Giannetii BM, et al. Effect of trospium chloride on urodynamic parameters in patients with detrusor hyperreflexia due to spinal cord injuries. Urol Int. 1991;47:138–43.

    Article  CAS  PubMed  Google Scholar 

  42. Madersbacher H, Stohrer M, Richter R, et al. Trospium chloride versus oxybutynin: a randomized, double- blind, multicentre trial in the treatment of detrusor hyper- reflexia. Br J Urol. 1995;75:452–6.

    Article  CAS  PubMed  Google Scholar 

  43. Menarini M, Del Popolo G, Di Benedetto P, et al. Trospium chloride in patients with neurogenic detrusor overactivity: is dose titration of benefit to patients? Int J Clin Pharmacol Ther. 2006;44:623–32.

    Article  CAS  PubMed  Google Scholar 

  44. Stohrer M, Madersbacher H, Richter R, et al. Efficacy and safety of propiverine in SCI-patients suffering from detrusor hyperreflexia—a double-blind, placebo-controlled clinical trial. Spinal Cord. 1999;37(3):196–200.

    Article  CAS  PubMed  Google Scholar 

  45. Stohrer M, Murtz G, Kramer G, et al. Efficacy and tolerability of propiverine hydrochloride extended-release compared with immediate-release in patients with neurogenic detrusor overactivity. Spinal Cord. 2013;51:419–23. https://doi.org/10.1038/sc.2012.174.

    Article  PubMed  CAS  Google Scholar 

  46. Stöhrer M, Mürtz G, Kramer G, et al. Propiverine compared to oxybutynin in neurogenic detrusor overactivity—results of a randomized, double-blind, multicenter clinical study. Eur Urol. 2007;51:235–42. https://doi.org/10.1016/j.eururo.2006.03.016.

    Article  PubMed  CAS  Google Scholar 

  47. Wollner J, Pannek J. Initial experience with the treatment of neurogenic detrusor overactivity with a new beta-3 agonist (mirabegron) in patients with spinal cord injury. Spinal Cord. 2016;54:78–82. https://doi.org/10.1038/sc.2015.195.

    Article  PubMed  CAS  Google Scholar 

  48. Wada N, Shimizu T, Takai S, et al. Combinational effects of muscarinic receptor inhibition and β3-adrenoceptor stimulation on neurogenic bladder dysfunction in rats with spinal cord injury. Neurourol Urodyn. 2016;36:1039–45. https://doi.org/10.1002/nau.23066.

    Article  PubMed  CAS  Google Scholar 

  49. Nitti VW, Auerbach S, Martin N, et al. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol. 2013;189:1388–95. https://doi.org/10.1016/j.juro.2012.10.017.

    Article  PubMed  CAS  Google Scholar 

  50. Nitti VW, Rosenberg S, Mitcheson DH, et al. Urodynamics and safety of the β3-Adrenoceptor agonist mirabegron in males with lower urinary tract symptoms and bladder outlet obstruction. J Urol. 2013;190:1320–7. https://doi.org/10.1016/j.juro.2013.05.062.

  51. Pacher P, Kecskemeti V. Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns? Curr Pharm Des. 2004;10:2463–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Amend B, Hennenlotter J, Schäfer T, et al. Effective treatment of neurogenic detrusor dysfunction by combined high-dosed antimuscarinics without increased side-effects. Eur Urol. 2008;53:1021–8. https://doi.org/10.1016/j.eururo.2008.01.007.

    Article  PubMed  CAS  Google Scholar 

  53. Cameron AP, Clemens JQ, Latini JM, McGuire EJ. Combination drug therapy improves compliance of the neurogenic bladder. J Urol. 2009;182:1062–7. https://doi.org/10.1016/j.juro.2009.05.038.

    Article  PubMed  Google Scholar 

  54. Tanaka I, Nagase K, Tanase K, et al. Improvement in neurogenic detrusor overactivity by peripheral C fiber’s suppression with cyclooxygenase inhibitors. J Urol. 2010;183:786–92. https://doi.org/10.1016/j.juro.2009.09.071.

    Article  PubMed  CAS  Google Scholar 

  55. Kumar A, Prabha R, Paul T, et al. Tramadol inhibits the contractility of isolated caprine detrusor muscle. Auton Autacoid Pharmacol. 2012;32:15–22. https://doi.org/10.1111/j.1474-8673.2012.00470.x.

    Article  PubMed  CAS  Google Scholar 

  56. Schurch B, Stohrer M, Kramer G, et al. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol. 2000;164:692–7.

    Article  CAS  PubMed  Google Scholar 

  57. Rovner E, Kohan A, Chartier-Kastler E, et al. Long-term efficacy and safety of onabotulinumtoxinA in patients with neurogenic detrusor overactivity who completed 4 years of treatment. J Urol. 2016;196:801–8. https://doi.org/10.1016/j.juro.2016.04.046.

    Article  PubMed  CAS  Google Scholar 

  58. Pannek J, Blok B, Castro-Diaz D, et al. Guidelines on neurogenic lower urinary tract dysfunction. Eur Urol. 2009;56(1):81–8.

    Article  PubMed  Google Scholar 

  59. Agrawal M, Joshi M. Urodynamic patterns after traumatic spinal cord injury. J Spinal Cord Med. 2015;38:128–33.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Blaivas JG, Sinha HP, Zayed AAH, Labib KB. Detrusor-external sphincter dyssynergia. J Urol. 1981;125:542–4.

    Article  CAS  PubMed  Google Scholar 

  61. Stoffel JT. Detrusor sphincter dyssynergia: a review of physiology, diagnosis, and treatment strategies. Trans Androl Urol. 2016;5:127–35.

    Article  Google Scholar 

  62. Bushman W, Steers WD, Meythaler JM. Voiding dysfunction in patients with spastic paraplegia: urodynamic evaluation and response to continuous intrathecal baclofen. Neurourol Urodyn. 1993;12:163–70.

    Article  CAS  PubMed  Google Scholar 

  63. Hackler RH, Broecker BH, Klein FA, Brady SM. A clinical experience with dantrolene sodium for external urinary sphincter hypertonicity in spinal cord injured patients. J Urol. 1980;124:78–80.

    Article  CAS  PubMed  Google Scholar 

  64. Chancellor MB, Erhard MJ, Rivas DA. Clinical effect of alpha-1 antagonism by terazosin on external and internal urinary sphincter function. J Am Paraplegia Soc. 1993;16:207–14.

    Article  CAS  PubMed  Google Scholar 

  65. Dykstra DD, Sidi AA, Scott AB, et al. Effects of botulinum a toxin on detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol. 1988;139:919–22.

    Article  CAS  PubMed  Google Scholar 

  66. Chen S, Bih L, Huang Y, et al. Effect of single botulinum toxin A injection to the external urethral sphincter for treating detrusor external sphincter dyssynergia in spinal cord injury. J Rehabil Med. 2008;40:744–8. https://doi.org/10.2340/16501977-0255.

    Article  PubMed  Google Scholar 

  67. Utomo E, Groen J, Blok BF. Surgical management of functional bladder outlet obstruction in adults with neurogenic bladder dysfunction. Cochrane Database Syst Rev. 2014;(5):CD004927. https://doi.org/10.1002/14651858.CD004927.pub4.

  68. Dykstra DD, Sidi AA. Treatment of detrusor-sphincter dyssynergia with Botulinum A toxin: a double-blind study. Arch Phys Med Rehabil. 1990;71(1):24–6.

    PubMed  CAS  Google Scholar 

  69. Phelan MW, Franks M, Somogyi GT, et al. Botulinum toxin urethral sphincter injection to restore bladder emptying in men and women with voiding dysfunction. J Urol. 2001;165:1107–10.

    Article  CAS  PubMed  Google Scholar 

  70. Mariappan P, Alhasso A, Ballantyne Z, et al. Duloxetine, a serotonin and noradrenaline reuptake inhibitor (SNRI) for the treatment of stress urinary incontinence: a systematic review. Eur Urol. 2007;51:67–74. https://doi.org/10.1016/j.eururo.2006.08.041.

    Article  PubMed  CAS  Google Scholar 

  71. Wilson JLL, Miranda CA, Knepper MA. Vasopressin and the regulation of aquaporin-2. Clin Exp Nephrol. 2013;17:751–64. https://doi.org/10.1007/s10157-013-0789-5.

    Article  PubMed  CAS  Google Scholar 

  72. Bosma R, Wynia K, Havlikova E, et al. Efficacy of desmopressin in patients with multiple sclerosis suffering from bladder dysfunction: a meta-analysis. Acta Neurol Scand. 2005;112:1–5. https://doi.org/10.1111/j.1600-0404.2005.00431.x.

    Article  PubMed  CAS  Google Scholar 

  73. Goh MY, Millard MS, Wong ECK, et al. Diurnal blood pressure and urine production in acute spinal cord injury compared with controls. Spinal Cord. 2017;55:39–46. https://doi.org/10.1038/sc.2016.100.

    Article  PubMed  CAS  Google Scholar 

  74. Szollar SM, Dunn KL, Brandt S, Fincher J. Nocturnal polyuria and antidiuretic hormone levels in spinal cord injury. Arch Phys Med Rehabil. 1997;78:455–8.

    Article  CAS  PubMed  Google Scholar 

  75. Eldahan KC, Rabchevsky AG. Autonomic dysreflexia after spinal cord injury: systemic pathophysiology and methods of management. Auton Neurosci. 2017;209:1–12. https://doi.org/10.1016/j.autneu.2017.05.002.

    Article  Google Scholar 

  76. Chancellor MB, Erhard MJ, Hirsch IH, Stass WE Jr. Prospective evaluation of terazosin for the treatment of autonomic dysreflexia. J Urol. 1994;151:111–3.

    Article  CAS  PubMed  Google Scholar 

  77. Chan YY, Sandlin SK, Kurzrock EA, Osborn SL. The current use of stem cells in bladder tissue regeneration and bioengineering. Biomedicine. 2017;5:4. https://doi.org/10.3390/biomedicines5010004.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    Casey G. Kowalik, Sophia Delpe & Roger Dmochowski

Authors
  1. Casey G. Kowalik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sophia Delpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roger Dmochowski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roger Dmochowski .

Editor information

Editors and Affiliations

  1. Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA

    Roger Dmochowski

  2. Department of Urology, Radboud University, Nijmegen, The Netherlands

    John Heesakkers

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kowalik, C.G., Delpe, S., Dmochowski, R. (2018). Pharmacologic Management of Neurogenic Lower Urinary Tract Dysfunction. In: Dmochowski, R., Heesakkers, J. (eds) Neuro-Urology. Springer, Cham. https://doi.org/10.1007/978-3-319-90997-4_21

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-90997-4_21

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-90995-0

  • Online ISBN: 978-3-319-90997-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation