The treatment of NLUTD centers on protecting the upper urinary tract, managing urinary incontinence, and ultimately improving the patient’s quality of life. In order to avoid renal injury, it is necessary to maintain intravesical pressure within safe limits during both the filling and voiding phase of bladder function.9
Identifying exacerbating factors, modifying behavior patterns, reducing infections, biofeedback, and pelvic floor strengthening are the mainstay of conservative management. Current and emerging treatments for NLUTD are summarized in .
Summary of current and emerging therapeutic options for neurogenic lower urinary tract dysfunction
Pharmacologic treatment of NLUTD using antimuscarinic drugs is well established. Muscarinic receptor antagonists act by binding to post-synaptic muscarinic receptors, thereby stabilizing the detrusor muscle and reducing involuntary contractions. A recent systematic review found greater symptomatic improvement and significant reduction in intravesical pressures when compared with placebo.10
Our systematic review did not find any studies reporting quality of life outcomes. It must also be noted that because muscarinic receptors are not confined to the urinary tract, side effects such as dry mouth and constipation limit their tolerability and long-term patient compliance with treatment. This is even moreso the case in patients with NLUTD because higher doses of antimuscarinic agents are required compared with a non-neurogenic population.11
Drugs may also be required to decrease the outlet resistance by relaxing the external urinary sphincter. However, these do not exist and so alpha antagonists may be used in selected cases to relax the bladder neck sphincter instead, which may improve bladder emptying.12
In a small cohort of 10 men with spinal cord injury and upper tract stasis, use of alpha blockers has been shown to resolve upper tract stasis in men who used reflex voiding.13
Other methods to improve emptying and keep intravesical pressures low involves use of reflex voiding with suprapubic tapping and catheterization, utilizing either intermittent or indwelling catheters. Intermittent catheterization is performed by the patient or carers 4–6 times a day. The suitability of this depends on correct aseptic technique, good hand function, motivation, and adequate frequency to ensure bladder volumes of less than 400 mL.5
There is a significant risk of urinary tract infection in patients who are unable to empty their bladder, and intermittent catheterization may be suitable in these patients. Complications include urethral trauma, false passages, and urine infections. Occasionally, indwelling catheters may be the only practical option in patients with poor hand function not suitable for surgery. These should be avoided long term due to their risk of infection, trauma, and malignant change in the bladder.14
Bladder rehabilitation techniques using electrical and magnetic stimulation both externally and intravesically have been shown to have benefits, albeit primarily in pilot studies with small cohorts of patients.15
There is a need for larger studies to further evaluate this as a treatment option. Where conservative measures have failed, more invasive treatment options are used. Procedures to decrease detrusor contractility include botulinum toxin injection into the detrusor, cystoplasty, and bladder autoaugmentation. Only sacral neuromodulation has been used to increase detrusor contractility. In patients with sphincteric incontinence, sphincter augmentation, artificial urinary sphincter, and bladder neck/urethral reconstruction are valid interventions, but only where detrusor function is under control and bladder pressures are low. Finally, procedures to decrease sphincteric resistance include an external sphincterotomy, urethral stenting, and botulinum toxin injection into the sphincter.
In patients with increased intravesical pressures who are able to empty the bladder, bladder augmentation by replacing or increasing the bladder capacity and thereby reducing intravesical pressure is a well established treatment. A Clam cystoplasty incorporates small intestine into a small contracted bladder. It must be noted that patients are often young, so long-term complications in particular need to be carefully considered. These include recurrent infection, stone formation, metabolic disturbance, perforation, and potential malignant changes.16
Nevertheless, success rates at 5 years are in excess of 90%.17
Beyond bladder augmentation, urinary diversion may be considered in order to protect the upper urinary tract, especially in the context of high detrusor pressures without an adequate method of urethral emptying. This should be a continent diversion primarily, although incontinent diversions may be appropriate in some patients where catheterization is not possible.
Of increasing use in patients refractory to conservative and medical management but prior to significant surgery is sacral nerve stimulation or sacral neuromodulation. First described by Schmidt and Tanagho in 1979, the technique stimulates afferents at the sacral level in order to reduce detrusor overactivity.18
Success rates are in the region of 60%–70%, and this technique may be effective for overactive and underactive detrusor function.19
In patients with sphincteric incontinence, techniques to increase outlet resistance may be employed only if bladder pressures are low. The least invasive of these are bulking agents, but their success rates are in the region of 20%–50%.20
The artificial urinary sphincter has the highest success rate of around 70%, although the procedure suffers from the complications listed for a foreign body implant and requires revision after a number of years.21
Lastly, procedures to decrease sphincteric resistance include sphincterotomy and urethral stents. External sphincterotomy is the gold standard for treating detrusor sphincter dyssynergia and often needs repeating. Stents may be temporary (Memokath®
) or permanent (Urolume®
). Complications include encrustation, migration, development of autonomic dysreflexia, and subsequent stricture formation.22
For patients in whom pharmacological treatment is not efficacious or is poorly tolerated, botulinum toxin is often considered before undertaking invasive surgery. It may be used to reduce detrusor overactivity or to relax the external urinary sphincter in detrusor sphincter dyssynergia. The remainder of this review considers the mechanism of action and evidence for botulinum toxin in the treatment of these two conditions.