Resource: Neurogenic Detrusor Overactivity

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Resource:
Neurogenic Detrusor Overactivity

Epidemiology and description of indication


Neurogenic bladder is a dysfunction due to alterations in the neural control of bladder function, often leading to urinary incontinence. It is observed in patients with a neurological disease, such as multiple sclerosis, Parkinson’s disease and stroke, but is particularly frequent after spinal cord injury (SCI), affecting up to 85-90% of this patient population [1- Cameron AP et al. J Urol. 2010]. While the average age at injury is 40 years, two peaks are observed, with the first concerning young men between the ages of 15 and 29 years and the second concerning older adults.

Depending on the location of the injury along the spinal cord, different patterns of neurogenic bladder are observed. Above the level of the L1-L2 vertebrae, the lesions are said supra-sacral and most often lead to neurogenic detrusor overactivity (NDO). This condition is characterized by irregular and uncontrolled contractions of the detrusor, the muscle that lines the bladder, and is responsible for various degrees of incontinence. In addition, supra-sacral spinal cord injuries are often associated with a loss of coordination between detrusor contraction and external striated urethral sphincter relaxation for voiding, a condition termed detrusor-sphincter dyssynergia (DSD), which, together with NDO, leads to urine retention and high bladder pressure, causes urine reflux to the kidneys and favors the development of recurrent urinary tract infections (UTIs), both of which lead to renal damage over time.

Urological complications are the major reason for rehospitalization of SCI patients, their leading cause of mortality in developing countries and a significant economic burden on healthcare systems [2-Paker N. et al, International Journal of Rehabilitation Research 2006, 3-DeJong G. et al,Archives of Physical Medicine and Rehabilitation 2003, 4 - World Health Organization (WHO). International perspectives on spinal cordinjury; 2013, 5- White B. A. B. et al, Journal of Neurotrauma 2017]. From a humane point of view, the management of bladder dysfunctions severely compromises a patient’s well-being: it is time-consuming, often complicated and may require assistance from a caregiver, but above all, it impacts on an individual’s social life, independence and dignity. Treating NDO must therefore aim at preventing complications, preserving renal function and decreasing incontinence, while taking into consideration the patient’s expectations and ultimately improving their quality of life.


Current management of NDO

Over the past decades, the incidence of death in SCI patients as a consequence of urological complications has greatly decreased due to important progress in treating lower urinary tract dysfunctions and in particular NDO [6- Capoor J, Stein AB. Phys Med Rehabil Clin N Am. 2005]. Several treatment options are available for NDO, all of which include an approach to counter uncontrolled detrusor contractions, and a method for bladder drainage. The latter is preferentially achieved with clean intermittent catheterization (CIC), a catheter that is inserted by either the patient or their caregiver several times a day to empty the bladder. Although no better alternative currently exists, CIC increases the incidence of UTIs [7- Wyndaele JJ. Nat Rev Urol. 2016]. Several options exist however to prevent uncontrolled detrusor contractions.

Pharmacological approaches
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Oral antimuscarinics have been the method of choice to treat detrusor overactivity for decades in both adults and pediatric patients with SCI as a first line treatment. Antimuscarinics, also called anticholinergics, act by binding muscarinic receptors on the detrusor, preventing binding of acetylcholine, a neurotransmitter that normally triggers detrusor muscle contraction. As a result, antimuscarinics inhibit involuntary bladder contractions.

The most common antimuscarinic agent is oxybutynin, which displays a proven efficacy, but is associated with a number of side effects that include dry mouth, constipation, urinary retention, dizziness, blurred vision and importantly, an increased risk of dementia [7- Wyndaele JJ. Nat Rev Urol. 2016, 8-Harnod T. et al, Sci Rep, 2021].

Other antimuscarinics include trospium chloride, propiverine, tolterodine, which are slightly better tolerated than oxybutynin, albeit with a similar efficacy and an equivalent panel of side effects.

Key treatment options for the management of neurogenic detrusor overactivity, together with their advantages and disadvantages.

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While considerable progress have been achieved in the management of NDO, additional efforts are still required to minimize side effects, prevent medical complications such as recurrent UTIs, and significantly improve the patients’ quality of life by ultimately alleviating the need for CIC.

References

  1. Cameron AP, Wallner LP, Tate DG, Sarma AV, Rodriguez GM, Clemens JQ. Bladder management after spinal cord injury in the United States 1972 to 2005. J Urol. 2010 Jul;184(1):213-7. doi: 10.1016/j.juro.2010.03.008. Epub 2010 May 15. PMID: 20478597.

  2. Paker, N., Soy, D., Kesikta, N., Nur Bardak, A., Erbil, M., Ersoy, S., & Ylmaz, H. (2006). Reasons for rehospitalization in patients with spinal cord injury: 5 years’ experience. International Journal of Rehabilitation Research, 29(1), 71–76. https://doi.org/10.1097/01.mrr.0000185953.87304.2a

  3. DeJong, G., Tian, W., Hsieh, C.-H., Junn, C., Karam, C., Ballard, P. H., Smout, R. J., Horn, S. D., Zanca, J. M., Heinemann, A. W., Hammond, F. M., & Backus, D. (2013). Rehospitalization in the First Year of Traumatic Spinal Cord Injury After Discharge From Medical Rehabilitation. Archives of Physical Medicine and Rehabilitation, 94(4), S87–S97. https://doi.org/10.1016/j.apmr.2012.10.037

  4. World Health Organization (WHO). International perspectives on spinal cordinjury; 2013 [Cited: 2021 January; available from: http://apps.who.int/iris/bitstream/10665/94190/1/9789241564663_eng.pdf?ua=1]

  5. White, B. A. B., Dea, N., Street, J. T., Cheng, C. L., Rivers, C. S., Attabib, N., Kwon, B. K., Fisher, C. G., & Dvorak, M. F. (2017). The Economic Burden of Urinary Tract Infection and Pressure Ulceration in Acute Traumatic Spinal Cord Injury Admissions: Evidence for Comparative Economics and Decision Analytics from a Matched Case-Control Study. Journal of Neurotrauma, 34(20), 2892–2900. https://doi.org/10.1089/neu.2016.4934

  6. Capoor J, Stein AB. Aging with spinal cord injury. Phys Med Rehabil Clin N Am. 2005 Feb;16(1):129-61. doi: 10.1016/j.pmr.2004.06.016. PMID: 15561548.

  7. Wyndaele JJ. The management of neurogenic lower urinary tract dysfunction after spinal cord injury. Nat Rev Urol. 2016 Dec;13(12):705-714. doi: 10.1038/nrurol.2016.206. Epub 2016 Oct 25. PMID: 27779229.

  8. Harnod, T., Yang, YC., Chiu, LT. et al. Use of bladder antimuscarinics is associated with an increased risk of dementia: a retrospective population-based case–control study. Sci Rep 11, 4827 (2021). https://doi.org/10.1038/s41598-021-84229-2

  9. Schurch B. Botulinum toxin for the management of bladder dysfunction. Drugs. 2006;66(10):1301-18. doi: 10.2165/00003495-200666100-00001. PMID: 16903766.

  10. Hsieh PF, Chiu HC, Chen KC, Chang CH, Chou EC. Botulinum toxin A for the Treatment of Overactive Bladder. Toxins (Basel). 2016 Feb 29;8(3):59. doi: 10.3390/toxins8030059. PMID: 26938559; PMCID: PMC4810204.

  11. Schurch B, Stöhrer 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. J Urol. 2000 Sep;164(3 Pt 1):692-7. doi: 10.1097/00005392-200009010-00018. PMID: 10953127.

  12. Mehta S, Hill D, McIntyre A, Foley N, Hsieh J, Ethans K, Teasell RW, Loh E, Welk B, Wolfe D. Meta-analysis of botulinum toxin A detrusor injections in the treatment of neurogenic detrusor overactivity after spinal cord injury. Arch Phys Med Rehabil. 2013 Aug;94(8):1473-81. doi: 10.1016/j.apmr.2013.04.011. Epub 2013 Apr 28. PMID: 23632286.

  13. Wyndaele JJ, Van Dromme SA. Muscular weakness as side effect of botulinum toxin injection for neurogenic detrusor overactivity. Spinal Cord. 2002 Nov;40(11):599-600. doi: 10.1038/sj.sc.3101318. PMID: 12411968.

  14. Chen LC, Kuo HC. Current management of refractory overactive bladder. Low Urin Tract Symptoms. 2020 May;12(2):109-116. doi: 10.1111/luts.12304. Epub 2020 Feb 19. PMID: 32073742.