How can neuromodulation be so efficacious? The answer lies in its mechanism of action.
How can neuromodulation be so efficacious in patients who have already failed conventional therapy? The answer lies in its mechanism of action.
SNS modulates afferent neural activity, activating specific inhibitory pathways. Low-stimulation currents applied to the A-delta myelinated sacral roots excite central inhibitory pathways, which modulate the activity of somatic nerves in the external urethral sphincter and pelvic floor. SNS indirectly inhibits the afferent-mediated excitatory reflexes by suppressing inter-neuronal transmission within the sacral cord without inhibiting voluntary voiding.
Efforts to miniaturize the implantable device have spurred development of a less-invasive pudendal nerve stimulation (PNS) system, which is currently under clinical investigation (see article). The theory of efficacy is similar to that for SNS: Direct inhibitory input to the bladder preganglionic nerves via stimulation of the pudendal nerve suppresses bladder overactivity. Pudendal afferent input to the sacral cord can inhibit supra-spinally mediated voiding dysfunction.
Data on a leadless, rechargeable, implantable micro-stimulator, which is percutaneously placed at the pudendal nerve, were presented at the recent AUA annual meeting in Atlanta. The device, known as bion (Advanced Bionics, Santa Clarita, CA) is currently being evaluated in a prospective, randomized, sham-controlled study for the chronic treatment of frequency, urgency, and urge incontinence.
In addition, researchers have shown the feasibility of placing the SNS quadripolar lead at the pudendal nerve, via a posterior approach. Early results demonstrate efficacy that may be superior to that of conventional SNS.
Finally, neuromodulation is an attractive treatment for voiding dysfunction associated with interstitial cystitis. In the only prospective evaluation of this approach in patients with IC refractory to standard therapies, >85% of patients in the University of Arizona cohort showed >50% improvement in voiding dysfunction and pelvic pain.
However, longer follow-up has demonstrated that neuromodulation is often not satisfactory as a monotherapy, but, rather, must be combined with behavioral treatments, pharmacotherapy, hydrodistention, and/or intravesical instillations. With multimodal therapy, 70% to 75% of the IC cohort remains >50% improved at a median of 4 years follow-up.
In conclusion, neuromodulation is becoming more popular as a treatment of voiding dysfunction with or without pelvic pain. Pudendal nerve stimulation may offer an alternative to SNS, with the potential advantages of more focused afferent stimulation, miniaturization, minimal invasiveness, and MRI safety.
Dr. Comiter, is chief, section of urology; director, female urology and urodynamics; and associate professor of surgery and instructor in obstetrics and gynecology at the University of Arizona Health Sciences Center, Tucson.