Minimally invasive treatments
Patients with NGB who have refractory detrusor overactivity may benefit from minimally invasive treatment. Refractory detrusor overactivity is marked by persistent urgency, frequency, and incontinence, and remains bothersome despite oral pharmacologic therapy.
Sacral neuromodulation. Although this approach is approved by the U.S. Food and Drug Administration (FDA) for the treatment of urinary retention and the symptoms of overactive bladder, its safety and efficacy have not been established for patients with neurologic disease origins. An alternative treatment option in patients with voiding dysfunction and chronic pelvic pain, it is generally performed in stages to identify responders; those who respond proceed to full implantation of pulse generator and leads.
Intravesical drug delivery. Neurogenic overactivity can be decreased for several months by intravesical instillation of agents that desensitize afferent C-fibers in the bladder. Sensation is restored when the sensory nerves regenerate. Higher levels of anticholinergics such as oxybutynin can be increased and adverse effects decreased by avoiding hepatic first-pass metabolism.24
Vanilloid compounds, capsaicin, and resiniferatoxin have been shown to be effective in refractory urge incontinence in adults with SCI and MS. Further studies are needed to determine long-term efficacy and safety.25 Advances in development of intravesical drug delivery, including the use of liposomal nanoparticles, will help improve management of symptoms of the lower urinary tract.26
Botulinum neurotoxin (BoNT) injection.Cystoscopic injections of BoNT modulate acetylcholine and other biochemical messengers at presynaptic nerve terminals and noncholinergic mechanisms in the detrusor smooth muscle,27 preventing detrusor contraction and leading to transient smooth muscle paralysis and symptom alleviation. A broader mechanism of action has been proposed that suggests BoNT blocks release of acetylcholine, ATP, and substance P, leading to central desensitization and effectiveness in detrusor overactivity.28
In August 2011, the FDA approved the use of onabotulinumtoxinA (Botox) injection to treat urinary incontinence in patients with NDO who have failed or cannot tolerate the adverse effects of anticholinergic therapy.29 Although three other BoNT serotype preparations are available—abobotulinumtoxinA (Dysport), incobotulinumtoxinA (Xeomin), and rimabotulinumtoxinB (Myobloc)—they are not approved to treat NDO and cannot be used interchangeably.30
An initial 24-week study found that onabotulinumtoxinA 200 U and 300 U clinically significantly decreased signs and symptoms of urinary incontinence caused by NDO in 59 patients due to SCI or MS vs. placebo.31
The FDA approval was based on results of two subsequent phase 3 randomized clinical studies involving 691 patients.32,33 The studies assigned patients with NDO resulting from SCI or MS not adequately managed with anticholinergics to onabotulinumtoxinA 200 U, 300 U, or placebo. Primary end point was changed from baseline in weekly urinary incontinence episodes at week 6. Patients in the onabotulinumtoxinA 200 U and 300 U arms had significant decreases in weekly frequency of incontinence episodes vs. placebo and had similar improvements in incontinence episodes, urodynamic parameters, and health-related quality-of-life scores (Figure 1).32-34
OnabotulinumtoxinA is injected intramuscularly at multiple sites throughout the bladder,35 in an outpatient procedure. The recommended dose of onabotulinumtoxinA is 200 U per treatment and should not be exceeded. Patients may be considered for reinjection when the clinical effect of the previous injection diminishes (median 42-48 weeks in clinical studies) but no sooner than 12 weeks from the prior bladder injection.36
The most common adverse events associated with intravesical BoNT injection are incomplete bladder emptying and urinary tract infections.27 Contraindications to onabotulinumtoxinA are active infection and known hypersensitivity to agents; relative contraindications include preexisting neuromuscular disorders and concomitant use of agents interfering with neuromuscular transmission; pregnancy (Class C) and nursing mothers; and bladder outlet obstruction. Incidence of autonomic dysreflexia may occur in patients treated for detrusor overactivity associated with a neurologic condition that requires prompt medical therapy.36
Surgical options include transurethral sphincterotomy, endourethral stents, urethral and bladder neck procedures, bladder augmentation, and urinary diversion (Table 3). Long-term follow-up of patients with NDO must be conducted, as changes in detrusor compliance and urodynamic patterns may occur over time.37