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Advances in Urogynecology

Sacral Nerve Stimulation for Pelvic Floor Disorders

Michael B. Noone, MD; Brett J. Vassallo, MD

Since humanity has endeavored to facilitate healing to relieve human suffering, many different tools have been applied for this purpose. Approaches have included both plant-derived and chemically and biologically synthesized medications. Physical manipulations of tissue for therapy have evolved into many minimally invasive surgeries and reconstructive techniques with manufactured tissue replacements. One alternative in the manipulation of physiologic events has involved electrical therapy.

Neurophysiologic abnormalities have been described in pelvic floor disorders, and various electrophysiologic techniques have been used to treat these dysfunctions. Kegel exercises are an example of these techniques. Electrical stimulation of the pelvic floor muscles through surface or percutaneous needle electrodes has also been employed.

There is now a more exact means of providing therapy with direct nerve stimulation to permit physiologic manipulation of bladder activity to effect treatment of bladder dysfunctions. Sacral neuromodulation with a permanent, implantable neuroprosthetic device (Interstim) was approved by the US Food and Drug Administration (FDA) in 1997, and was employed in thousands of patients in Europe prior to that date. The evolution of the technique to allow for a less invasive approach is making this type of treatment more readily available. This review discusses patient selection, reviews the theoretical mechanisms of electrophysiologic intervention for bladder dysfunction, describes how the technique has evolved, and provides current outcome data with respect to its use.

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PATIENT SELECTION

The FDA has currently approved sacral neuromodulation for three indications in patients with chronic voiding dysfunction who have inadequate response to more conservative therapies: urinary urge incontinence (UUI), urgency-frequency syndrome, and voiding difficulty (incomplete emptying or complete retention).

Urinary urge incontinence and urgency-frequency syndrome are similar in that they are due to chronic bladder overactivity—ie, the bladder fails to remain relaxed until an appropriate and desirable time to empty. In women with UUI, this overactivity can be due to hyperreflexia of the detrusor muscle or instability from a clinically apparent neurologic disorder. Urodynamically, such a disorder manifests as involuntary detrusor contractions, usually with concomitant loss of urine (motor urgency). Clinically, this disorder is defined as involuntary loss of urine associated with a strong urge to void.

Urgency-frequency syndrome is a related condition in that it is also associated with an unrelenting urge to void, clinically presenting as frequent small voids. Urinary frequency is defined as more than seven voids per day--although patients typically complain of more than one void per hour—and nocturia (two or more episodes of waking urgency to void during sleep). Urodynamically, the condition differs from UUI in that such patients do not display involuntary detrusor contractions and have a small capacity (sensory urgency). However, due to similar etiologic mechanisms, many patients present with both disorders. Interestingly, many such patients also manifest other abnormal sensory conditions, including urethral syndrome, pelvic pain, interstitial cystitis, irritable bowel syndrome, and fibromyalgia.

Many treatment modalities have been directed at these debilitating conditions. Antibiotics, antimuscarinic drugs, nonsteroidal anti-inflammatory medications, narcotics, behavioral modifications, and physical therapy (pelvic floor exercises) are all utilized with varying degrees of success. Patients who are refractory to such conservative interventions are appropriate candidates for more aggressive electrophysiotherapy, including sacral neuromodulation.

Somewhat paradoxically, patients who have the apparently dissimilar problem of nonobstructive urinary retention are also candidates for sacral neuromodulation. There is no strict definition of an abnormal postvoid residual volume, but the general rule for a normal residual volume is less than 50 mL of urine remaining in the bladder after a void of at least 200 mL. A less confusing but clinically similar group of patients are those who cannot initiate voiding (complete urinary retention). Both situations can be due to anatomic or functional abnormalities. Examples of anatomic etiologies include urethral strictures, iatrogenic obstruction (following surgery for incontinence), and obstruction due to advanced pelvic organ prolapse. Nonneurogenic functional cases (no identifiable neurologic disease or injury) have no readily diagnosable etiology. Such individuals have hypocontractile or acontractile detrusor muscles on urodynamic evaluation, and/or may be unable to relax their pelvic floor.

There are no clinical parameters to predict which patients will succeed with sacral neuromodulation. Therefore, all patients who may be candidates for this intervention should undergo a trial of conservative therapy prior to permanent implantation. Because the same quadripolar lead is used for both the testing period and the permanent implantation phase, the test stimulation has great utility.

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MECHANISM

Our understanding of the mechanism of action for sacral neuromodulation is limited. The pathophysiology of overactive detrusor symptoms and dysfunctions of bladder emptying have not been completely defined. Local detrusor myogenic factors, as well as pelvic and suprasacral neurologic dysfunctions, have been implicated. Suppression of overactive excitatory and inhibitory activity would be required for any therapy to treat both urgency-frequency/urge incontinence and inhibited bladder emptying. Restoration of the equilibrium of excitatory and inhibitory neurologic activity affecting bladder storage and micturition reflexes may be mediated by sacral nerve neuromodulation.¹ Thus, a single modality can treat both storage and micturition dysfunctions.

Patients with idiopathic voiding dysfunction are felt to respond to this therapy via suppression of an overactive guarding reflex. Elevated pelvic floor tone or spasticity with a resultant functional detrusor-sphincter dyssynergia can create this condition. For example, the inhibition of voiding after gynecologic surgery, vaginal delivery, or even hemorrhoid surgery may be related to a reactive increase in pelvic floor tone and engagement of the guarding reflex. Most patients overcome such acute insults and achieve resolution of normal function, but some have overactive suppression of normal voiding even in the absence of pelvic floor trauma or observed pelvic floor spasticity. In such individuals, sacral neuromodulation would act to block or down-regulate the overactive inhibition via pudendal nerve reflexes.

Overactive bladder symptoms have been attributed to excessive excitatory activity in either afferent or efferent arms of the pudendal nerve. Sacral nerve stimulation has been reported to provide somatic afferent inhibition of sensory processing in the spinal cord.^{3, 3} This action is also thought to inhibit supraspinally mediated overactive voiding via suppression of ascending sensory pathways.

Alternatively, the clinical reduction in symptoms may be via action of the efferent arm of pudendal nerve reflexes and the interaction of higher control mechanisms. As volitional pelvic floor contraction can suppress unstable bladder contractions, stimulation of sacral nerve roots may act on the pelvic floor to create this effect, reducing detrusor overactivity. This has been demonstrated in animal models.⁴

The actual mechanism for each individual may be as variable as the degrees of nerve dysfunction. Some patients may be responding because of action at the efferent arm mediated through the pudendal nerve, allowing stabilization of the pelvic floor. Others are responding via afferent stimulation. Beyond the immediate effects of sacral nerve stimulation are the unknown reactive effects of neurologic activity in autonomic systems subjected to chronic stimulation.

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TECHNIQUE

The origin of this technology goes back to the early 1970s, as years of study utilizing animal models gave way to feasible therapeutic approaches for human subjects. Over the past decade, there has been a remarkable evolution in how this treatment has been employed, improving the efficacy of the intervention and making the technique simpler and less invasive.

Early versions of sacral neuromodulation required placement of a percutaneous monopolar wire through a foramen needle. This was typically performed in the office. Proper placement of the needle (most typically in the third sacral foramen) was confirmed by visualization of the appropriate sensory and motor reflexes. Such placement was often assisted with ultrasonography and confirmed by postprocedure radiography. Patients then wore an external stimulating unit for approximately 1 week to determine whether they would be good candidates for placement of a permanent lead and stimulator. Such patients subsequently underwent surgery involving general anesthesia and a long, midline incision over the sacrum. Dissection was carried laterally to the sacral foramina. The lumbosacral fascia was opened, and the spinous muscle retracted to expose the periosteum (Figure 1). A foramen needle was advanced and, if proper motor responses were observed, the needle was removed and a permanent quadripolar lead was advanced into the foramen and tested. If good motor responses were observed again, this lead was anchored to the periosteum with permanent suture. The lead was then tunneled to another location—typically on the superior aspect of the ipsilateral buttocks—where a subcutaneous pocket was developed and a permanent generator was placed and attached to the lead. The patient would return several weeks later for programming.

While often clinically successful, this early technique had several drawbacks. As the nonpermanent test leads could not be tunneled under the skin or easily fixed in place, test periods were limited by concerns over lead migration and infection. One concern about the short 5- to 7-day test period was the inability to be certain if the benefit observed was authentic or due to placebo effect. Additionally, the dissection required for the permanent lead was extensive, necessitating general anesthesia and limiting the clinical assessment to the motor response as the patient was unable to verify any sensory response. Also, as a second lead was involved, the correlation between the test period and permanent treatment period was poor in some cases.

To overcome such limitations, a staged test/implant procedure with a single lead was developed. This became possible with the advent of a permanent, tined, quadripolar lead (Figure 2). This lead is placed for the test stimulation, and if successful, left in place and attached to the permanent stimulator—which is typically implanted 3 weeks later (Figure 3). The lead is placed percutaneously using a foramen needle, negating the need for a large incision and extensive dissection (Figure 4). Proper placement is greatly facilitated by fluoroscopy. There is no need to suture this lead to the periosteum because the lead is fixed in place by tines that are deployed by retracting the hollow foramen needle through which the lead is passed once proper placement is confirmed. The lead is tunneled through the subcutaneous fat to the future site of the permanent stimulator at the time of the initial lead placement, permitting longer testing periods. Because only mild sedation and local anesthesia are required, both motor and sensory responses can be assessed, and programming is typically performed in the operating room at the time of the implantation of the permanent stimulating device.

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CLINICAL RESULTS

Given that the patients who receive this therapy have failed most other customary treatments, the clinical results of sacral neuromodulation appear to be impressive. A prospective, randomized trial involving 98 patients who underwent permanent implantation after successful test stimulation for refractory urge incontinence found that 52% of subjects had no incontinent episodes for up to 18 months from the initiation of treatment. Another 24% of subjects reported a 50% or greater reduction in the number of incontinent episodes in the same follow-up period.5 A smaller study from Norway had similar results after 3 years; 14 subjects were followed for this length of time, of whom eight (57%) reported continence and five (36%) reported greater than 50% improvement.⁶

A prospective study of 51 patients with urgency-frequency syndrome followed for up to 2 years revealed that 88% of stimulated subjects (compared with 32% of controls) had a good clinical result as defined by significant differences on a validated quality-of-life measurement tool.⁷ There were also significant differences in the clinical parameters of volume voided (64% significant increase in the stimulation group versus 8% in controls) and number of voids per day (56% significant reduction versus 4%).

The efficacy of this technology for the treatment of urinary retention was shown in a prospective, randomized study of 68 subjects in which results from 24 subjects with implants were evaluated by comparing baseline symptoms with 18-month voiding-diary results. Fifty-eight percent of these patients were no longer using catheters, and an additional 13% had a greater than 50% reduction in the volume catheterized compared with baseline.⁸

One detail that may be easily lost in the interpretation of these studies, which for the most part included patients treated with the older technique (monopolar test stimulation and separate permanent quadripolar implant), is that only about 50% of the subjects studied actually had a good enough response to the test stimulation to warrant permanent implantation. When interpreting these results, it is important to realize that only the subset of patients who successfully responded to the test stimulation were included in the analysis. However, the newer technique appears to have a much higher test-to-implant rate, which may ultimately translate into greater degrees of successful treatment. In fact, data suggest that outcomes are improved with the newer technique. A study of 26 subjects comparing the traditional approach with the tined-lead approach found the test-to-implant rate was 52% compared with 94%.⁹ The reoperation rate was reduced from 43% to 0% due to the ability to assess the sensory response at the time of implantation, another benefit of the newer approach.

There have been some pilot studies that suggest new uses for this technology as well. Results for the use of sacral neuromodulation to treat fecal incontinence have been promising. One study showed a decrease in percentage of incontinent bowel movements from 40% to 3%, and these results correlated with improvements in objective functional testing of the anal sphincter.¹⁰ Leroi et al¹¹ have published findings from a small number of patients that suggest this technology may be efficacious in treating dual fecal and urinary incontinence as well.

Interstitial cystitis (IC) and other chronic pelvic pain syndromes have also been studied as possible indications for this therapy. Several studies have shown significant decreases in pain, narcotic usage, and irritative bladder symptoms.^{9, 12-15} Interestingly, as in the case of fecal incontinence, objective clinical correlates that can be used as markers for response to therapy have been identified for IC. Chai et al¹⁶ showed that neurostimulation not only improved symptoms in patients with IC, but also normalized levels of urinary heparin-binding epidermal growth factor and antiproliferative activity, two factors known to be altered in IC.

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CONCLUSION

While this technology clearly does not represent a panacea for all maladies of the pelvic floor, it is a novel approach that has proved to be clinically effective in significant percentages of patients who have failed all other therapies. For this reason, it behooves physicians caring for patients with these frustrating disorders to become familiar with this treatment. In the past, there has been a reluctance to embrace this technology because of the loss of efficacy from test to implant and the extent of the surgery required for the permanent implant. The modifications made to the procedure have addressed these concerns. Not only have they better enabled physicians to offer this modality to more patients, but they have also made the technique accessible to more physicians.

Michael B. Noone, MD, and Brett J. Vassallo, MD, are clinical assistant professors of obstetrics and gynecology, University of Illinois, Chicago.

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References

1. Schmidt RA. Advances in genitourinary neurostimulation. Neurosurgery. 1986;19(6):1041-1044.
2. Lavelle JP, Teahan S, Kim DY, Chancellor MB. Medical and minimally invasive treatment of incontinence. Rev Urol. 1999;1:111-120.
3. de Groat WC. Neuroanatomy and neurophysiology: innervation of the lower urinary tract. In: Raz S, ed. Female Urology, 2nd ed. Philadelphia, Pa: WB Saunders: 1996:28-42.
4. Mersdorf A, Schmidt RA, Tanagho EA. Urodynamic evaluation and electrical and pharmacologic neurostimulation. The rat model. Urol Res. 1993;21(3):199-209.
5. Schmidt RA, Jonas U, Oleson K, et al. Sacral nerve stimulation for the treatment of refractory urinary urge incontinence. Sacral Nerve Stimulation Study Group. J Urol. 1999; 162(2):352-357.
6. Hedlund H, Schultz A, Talseth T, Tonseth K, van der Hagen A. Sacral neuromodulation in Norway: clinical experience of the first three years. Scand J Urol Nephrol Suppl. 2002; 210:87-95.
7. Hassouna MM, Siegel SW, Nyeholt AA, et al. Sacral neuromodulation in the treatment of urgency-frequency syndromes: a multicenter study on efficacy and safety. J Urol. 2000; 163(6):1849-1854.
8. Jonas U, Fowler CJ, Chancellor MB, et al. Efficacy of sacral nerve stimulation for urinary retention; results 18 months after implantation. J Urol. 2001;165(1):15-19.
9. Peters KM, Carey JM, Konstandt DB. Sacral neuromodulation for the treatment of refractory interstitial cystitis: outcomes based on technique. Int Urogynecol J Pelvic Floor Dysfunct. 2003;14(4):223-228.
10. Matzel KE, Stadelmaier U, Hohenfellner M, Hohenberger W. Chronic sacral spinal nerve stimulation for fecal incontinence: long-term results with foramen and cuff electrodes. Dis Colon Rectum. 2001;44(1):59-66.
11. Leroi A, Michot F, Grise P, Denis P. Effect of sacral nerve stimulation in patients with fecal and urinary incontinence. Dis Colon Rectum. 2001;44(6):779-789.
12. Comiter CV. Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis: a prospective study. J Urol. 2003;169(4):1369-1373.
13. Peters K, Konstandt D. Sacral neuromodulation decreases narcotic requirements in refractory interstitial cystitis. BJU Int. 2004;93(6):777-779.
14. Everaert K, Devulder J, De Muynck M, et al. The pain cycle: implications for the diagnosis and treatment of pelvic pain syndromes. Int Urogynecol J Pelvic Floor Dysfunct. 2001;12(1):9-14.
15. Siegel S, Paszkiewicz E, Kirkpatrick C, Hinkel B, Oleson K. Sacral nerve stimulation in patients with chronic intractable pelvic pain. J Urol. 2001;166(5):1742-1745.
16. Chai TC, Zhang C, Warren JW, Keay S. Percutaneous sacral third nerve root neurostimulation improves symptoms and normalizes urinary HB-EGF levels and antiproliferative activity in patients with interstitial cystitis. Urology. 2000; 55(5):643-646.

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