Sacral Neuromodulation
Karen L. Noblett
Carly Crowder
Introduction
Sacral neuromodulation (SNM) is a guideline-recommended therapy by both the American Urological Association (AUA) and the American Society of Colon and Rectal Surgeons, with proven long-term success for urinary urgency incontinence (UUI), urinary urgency frequency, nonobstructive urinary retention (NOUR), and fecal incontinence. SNM was first approved for voiding dysfunction in the United States in 1997 (urgency incontinence) and 1999 (urinary urgency frequency and NOUR). In the United States, it took another 12 years before it gained the additional indication for the treatment of fecal incontinence in 2011. Initially, the therapy involved a more invasive surgical approach that included a large cutdown over the sacrum to secure the lead to the periosteum. This initial procedure was performed under general anesthesia and was typically reserved for the most refractory patients. However, early physician-initiated innovation evolved the therapy into a minimally invasive procedure that allowed it to be performed under local anesthesia in an outpatient setting.1 Historically, there has been only one commercially available SNM device (InterStim, Medtronic, Dublin, Ireland), which is a nonrechargeable neurostimulator with an estimated lifespan of 4.4 years.2 In late 2019, a second SNM device was approved by the U.S. Food and Drug Administration (FDA) for the bowel and bladder indications listed earlier. The Axonics device (Axonics Modulation Technologies, Irvine, CA) is a miniaturized, rechargeable neuromodulation system qualified to last a minimum of 15 years in the body. In mid-2020, Medtronic also gained FDA approval for InterStim Micro, their miniaturized, rechargeable SNM device, which is also designed to last 15 years. In early 2022, both Axonics and Medtronic received FDA approval for nonrechargeable SNM devices, the Axonics F15 recharge-free SNM system and the Medtronic InterStimX system, respectively. These devices have longer projected life in the body compared to the legacy device. Depending on program settings, the devices are expected to last 10 to 20 years.
This chapter reviews recent advancements in SNM therapy including updates in best practices for implant technique, technological innovations, and the new clinical literature relevant to contemporary practice. This chapter also provides some insight into potential future directions of neuromodulation for pelvic floor disorders.
DEFINITION, INDICATIONS AND MECHANISM OF ACTION
SNM involves placing a quadripolar lead adjacent to a sacral nerve root (typically S3) that is connected to a neurostimulator that delivers nonpainful, electrical pulses to the sacral nerves to modulate the reflexes that influence the bladder, bowels, sphincters, and pelvic floor musculature to improve or restore function (Fig. 17.1).
Currently approved and available devices in the United States include InterStim II, InterStim Micro, and InterStimX (Medtronic, Minneapolis, MN) and the Axonics R15 (rechargeable) and F15 (nonrechargeable) SNM systems (Axonics, Irvine, CA) which are shown in Figure 17.2. The features of these systems are compared in Figure 17.3.
Indications for Sacral Neuromodulation
Although SNM is not considered a first-line therapy for bladder or bowel control disorders, it is a minimally invasive treatment with proven long-term success. Current FDA-approved indications for SNM use include urgency incontinence, urinary urgency frequency, NOUR, and fecal incontinence.
Urinary urgency frequency, urinary urgency incontinence (overactive bladder)
SNM is indicated for patients with overactive bladder (OAB) with and without incontinence who fail conservative therapy and/or medical management, including those who experience intolerable side effects. The AUA guidelines for the treatment of OAB recommend SNM as a third-line therapy; however, a recent update to the guidelines suggests that it is not necessary for all patients to go through each line of treatment in a specific order because there are many factors to consider when deciding on the best treatment option for a particular patient. The AUA
guidelines specifically state, “The patient does not need to proceed through each line of therapy before considering the next. In other words, the lines of therapy, while representing a successive increase in risk or invasiveness, are not intended to represent a strict algorithm.” This would suggest that patients with OAB do not necessarily have to trial and fail medications before being offered SNM.3
guidelines specifically state, “The patient does not need to proceed through each line of therapy before considering the next. In other words, the lines of therapy, while representing a successive increase in risk or invasiveness, are not intended to represent a strict algorithm.” This would suggest that patients with OAB do not necessarily have to trial and fail medications before being offered SNM.3
 FIGURE 17.1 INS connected to the quadripolar lead at S3. (Courtesy of Axonics, Inc.) |
Nonobstructive urinary retention
SNM is also indicated as a treatment option for patients with NOUR.4 Urinary retention has historically been a challenging condition to manage with few viable treatment options available. Prior to the introduction of SNM, NOUR was typically managed with intermittent or continuous bladder catheterization, both of which can be uncomfortable and are associated with increased risk of bladder infections. SNM has proven to be an effective alternative to catheterization and has been shown to significantly improve the quality of life for this patient population.4
Fecal incontinence
SNM is indicated as a second-line therapy for fecal incontinence in patients who have failed conservative therapies. SNM can be ideal and is preferred in patients who have both urinary and bowel disorders. SNM can also be offered to patients with anal sphincter defects and is approved for sphincter defects up to 120°. Generally, 2 weeks of bowel symptoms are documented prior to, and during therapy (e.g., bowel diary), to assess efficacy of SNM treatment. Further anorectal physiology testing may be helpful in comprehensive evaluation of bowel disorders and identification of additional components of dysfunction but has not been shown to be predictive of success with SNM. Although this testing is not necessary prior to SNM, it may prove useful in guiding management.4
Further indications
Although considered off-label, other indications that have been treated with SNM include neurogenic bladder, bladder pain syndrome (BPS), chronic pelvic pain, and chronic constipation.
Neurogenic bladder
Although most SNM trials exclude patients with underlying neurologic conditions, there is no data to support this strategy, and, in fact, there is a growing body of evidence to support the use of SNM in this population and that overall safety outcomes are similar for both groups.5,6,7,8,9,10 Peters et al.11 reported OAB responder rates in both neurogenic and nonneurogenic patients. In this study, the test responder rate was similar for both patient populations, with an implantation rate of 89% and 89.6%, respectively, and the long-term therapy responder rate was 86% for neurogenic patients and 63% for nonneurogenic patients. These data suggest that SNM works well for patients with underlying neurologic conditions and also has a similar safety profile.
Bladder pain syndrome/interstitial cystitis
Although not FDA approved for this condition, SNM is an option for BPS/interstitial cystitis (IC) that is refractory to conservative therapies. SNM provides an effective long-term treatment option for refractory BPS.12 In a study by Maher et al.,13 13 of 15 patients (87%) reported a 50% reduction in bladder pain. Similarly, in a study of 17 patients conducted by Comiter,14 bladder pain was evaluated by visual analogue scale. In this noncontrolled study, patients reported a reduction in pain from 5.8 to 1.6 (P < .01), with 87% of patients reporting symptomatic improvement.14 In another study of 21 patients by Peters and Konstandt,15 a 36% reduction in morphine dose equivalents was demonstrated in their population, where 22% became narcotic free, and 95% reported moderate to marked reduction in pain. A systematic review and meta-analysis completed in 2017 indicated that SNM may be a safe and effective for treatment of refractory BPS/IC.16 Overall, 60% to 98% (pooled analysis demonstrated 84%) of patients report
symptom improvement, and explant rates are reported between 3% and 13%.16 The AUA endorses SNM in its treatment algorithm for BPS as the consensus of the review panel is that there is adequate data in the literature to support its endorsement.17
symptom improvement, and explant rates are reported between 3% and 13%.16 The AUA endorses SNM in its treatment algorithm for BPS as the consensus of the review panel is that there is adequate data in the literature to support its endorsement.17
 FIGURE 17.2 Available SNM devices in the United States. A: Axonics R15 INS and Axonics F15 INS. B: Medtronic Micro and Interstim II. C: Medtronic InterstimX. (A, courtesy of Axonics, Inc. B and C, © 2022 Medtronic. All rights reserved. Used with the permission of Medtronic.) |
Constipation
Although off-label in the United States, SNM is approved in Europe for the treatment of chronic constipation for patients with refractory symptoms for over 1 year and no evidence of a mechanically correctable cause. In studies evaluating SNM for use in constipation, it has been shown to induce pan-colonic propagating pressure waves and to increase bowel movement frequency.18,19 A recent study, evaluating the use of SNM for slow-transit constipation, showed a significant improvement in both colorectal transit time and Cleveland Clinic Constipation Scores at 6 months. However, at 60 months, 48% of patients had the neuromodulator removed.20 In a review article from 2013 that included 10 prior studies evaluating SNM in the treatment of constipation, a total of 225 SNM trials were performed with 125 going to permanent implant (55.5%).21 Of those implanted, 89.6% of patients with
permanent implants reported satisfaction with their SNM device. Overall, data on SNM therapy for constipation is conflicting and further studies to evaluate long-term efficacy are warranted.
permanent implants reported satisfaction with their SNM device. Overall, data on SNM therapy for constipation is conflicting and further studies to evaluate long-term efficacy are warranted.
 FIGURE 17.3 Comparison of the available SNM systems. (Courtesy of Axonics, Inc.) |
Mechanism of Action
Normal voiding
For infants and toddlers who have not yet achieved voluntary control over bladder function, a critical level of bladder distention is required to stimulate the voiding reflex. This sensory input, upon reaching the pontine micturition center, simultaneously allows for a coordinated detrusor contraction and concomitant urethral relaxation, thus facilitating urination. This is a primordial reflex pathway that allows for effective and efficient bladder emptying and prevents the bladder from over distending, causing injury. Gaining voluntary control over, and learning to suppress, this voiding reflex is a complex process that is mediated at a higher level in the cerebral cortex and generally begins to mature around age 2 years and can take as long as 7 years to fully develop. Continence is also maintained via an intact guarding reflex, which is a progressive, involuntary increase in the activity of the external urethral sphincter during bladder filling resulting in increased outlet resistance. Voluntary voiding is facilitated through stimulation of the excitatory efferent pathway, resulting in inhibition of the sympathetic system and pudendal nerve, and activation of the sacral parasympathetics.22
The causes of OAB, NOUR, and fecal incontinence can be multifactorial and are not completely understood. SNM treats bladder and bowel dysfunction by electrically modulating neural pathways via stimulation of a sacral nerve root (typically S3). For OAB, SNM most likely functions through two main pathways, with a third pathway that has also been suggested to play a role. These three pathways include the following:
Spinal reflex pathways that inhibit detrusor overactivity
Supraspinal areas in the brain that normalize bladder function
Direct and indirect effects on the urethral sphincter
Taken together, these indicate that SNM most likely works through local reflex pathways that influence bladder activity and also at higher levels in the brain that govern bladder function.
Spinal reflex pathway mechanism of action
In a study by DeGroat and Saum,23 it was demonstrated that sacral preganglionic outflow to the bladder receives inhibitory input from both somatic and visceral afferents. This suggests that nerves going to the bladder from the sacral nerve roots can be influenced by input from the pudendal nerve before actually affecting the bladder. Thus, activating these somatic afferents can inhibit detrusor/bladder function and improve OAB symptoms.
Given the low level of stimulation associated with SNM, it likely functions through the somatic afferents including the pudendal afferents because we know these nerves depolarize at lower levels than autonomic nerves. Studies have shown that activation of these somatic afferent nerves inhibits bladder sensory pathways and reflex bladder hyperactivity, thereby decreasing symptoms of OAB.24,25,26,27,28
Supraspinal pathway mechanism of action
Stimulating the somatic afferent nerves in a sacral spinal root (S3, S4, and/or pudendal) also sends signals to the higher centers in the central nervous system (CNS) that may restore normal communication between the brain and the bladder and thus normal function. SNM appears to normalize brain activity that is responsible for detrusor overactivity, bladder filling sensation, the sense of urge, and timing of micturition. One study using positron emission tomography scans has demonstrated changes in brain activity with SNM stimulation both in the on and off settings in patients with OAB. This study indicates that there is abnormal brain activity in these areas which become normalized with SNM active stimulation.29
Activation of the urethral sphincter
Direct activation of motor neurons innervating the striated urethral sphincter can lead to increased outlet resistance which ultimately is inhibitory to bladder reflex activity at the CNS level. In a similar manner, when you have an urge to urinate, if you contract your pelvic floor muscles, this leads to increased resistance/pressure in the urethra. This increased pressure triggers a reflex pathway back to the bladder that promotes bladder relaxation. This is the same concept with SNM. Indirect activation of the urethral sphincter may also occur via activation of afferent projections that influence the sympathetic tone to the urethral striated sphincter, thus promoting bladder relaxation.30
IMPLANT PROCEDURE
One of the advantages of SNM is that patients can undergo a test procedure to determine if the therapy is right for them. For surgeons, there is no other existing procedure that offers this advantage. Therapy for SNM is generally completed in two phases: The first phase is when a temporary lead (percutaneous nerve evaluation [PNE] lead) or a tined lead is placed along a sacral nerve root (generally S3) and stimulation of the nerve is conducted for a period of 3 to 14 days depending on the type of trial. Using a shared decision-making model, the patient and physician are able to determine if this therapy is effective and appropriate for their condition. If patients have a ≥50% improvement in symptoms and they are satisfied with their response, they go on to the second phase where the implantable neurostimulator (INS) is implanted. If the trial is inconclusive with a temporary (PNE) trial, patients can go on to a longer tined lead trial, or they may choose to pursue other treatment modalities.
The least invasive trial type is the PNE, also known as a basic evaluation. This type of trial can be completed in an office or surgery center and typically only requires local anesthesia, but monitored anesthesia care is also commonly used. The procedure is completed by placement of a temporary electrode wire in the S3 foramen without or without fluoroscopic guidance and is generally done bilaterally. The wire is then connected to a temporary, external pulse generator and worn by the patient for 3 to 7 days to evaluate if the therapy is effective.31 The PNE has several benefits including being less costly and less invasive and may require only one trip to the operating room (OR). Limitations of the PNE include lead migration because there is nothing internal to secure the lead, a shorter trial period, and potentially suboptimal wire placement if fluoroscopy guidance is not used. However, a recent randomized clinical trial demonstrated that the outcomes for PNEs performed without fluoroscopy was noninferior to those performed with fluoroscopy arguing against that last point.32
The second option for nerve stimulation testing is a staged procedure, where a tined lead is placed parallel to a sacral nerve root, typically S3, under fluoroscopic guidance. The S3 nerve root is the preferred target for
SNM because S3 is the main contributor to pelvic floor innervation.33 Patients are positioned prone in the OR to allow visualization of the S3 nerve responses including great toe dorsiflexion and bellows response. General anesthesia with paralytics and regional anesthesia must be avoided in order to visualize these responses.4
SNM because S3 is the main contributor to pelvic floor innervation.33 Patients are positioned prone in the OR to allow visualization of the S3 nerve responses including great toe dorsiflexion and bellows response. General anesthesia with paralytics and regional anesthesia must be avoided in order to visualize these responses.4
 FIGURE 17.4 Ideal needle placement in AP (A) and lateral (B) views. In the AP view, a needle is placed parallel and along the medial border of the foramen. In the lateral view, the needle is parallel to the fusion plate of S3 (red dotted line) and is approximately 1 cm above and sitting just at the anterior surface of the sacrum. |
After identification of the bony landmarks, a 3.5- or 5-inch foramen needle is placed such that it is parallel to the medial border of the foramen on the anteroposterior (AP) image and 1 cm above and parallel to the fusion plate on the lateral image (Fig. 17.4). The needle is only advanced to the anterior surface of the sacrum where the stimulation threshold is tested and considered acceptable if ≤2 mA.4 If greater than 2 mA, the needle should be redirected to find a better location in the foramen (tip: going back to the AP position on fluoroscopy can be helpful to troubleshoot if not getting the desired response). Once proper response is confirmed, the lead introducer is placed over a directional guide and advanced such that the radiolucent marker is approximately halfway through the bony plate (Fig. 17.5). This can be done under live fluoroscopy or with incremental advancement. Care should be taken not to advance the introducer too deep as this may create a false path for the lead to follow. It is recommended to use the curved stylet when introducing the lead so that it is able to follow the natural path of the nerve. Use of the curved stylet has been shown to have overall less amplitude requirements and is associated with better long-term outcomes as compared to the straight stylet.34,35 The quadripolar lead, which is self-anchored via deployable tines, is then placed such that ideal motor responses are achieved on all four electrodes, ideally at less than 2 mA. The length of the staged lead placement trial is generally 7 to 14 days,4,36 and there has been no evidence demonstrating benefit of performing a bilateral over a unilateral tined lead trial.37 Patients with at least a 50% improvement in symptoms during the trial period for either PNE or staged lead placement are considered a success and a candidate to progress to implant of the INS. PNE versus a staged trial was evaluated in a prospective trial by Borawski et al.38 This study showed a significantly
increased progression to implant placement with staged procedure versus PNE (88% vs. 46%, P < .02). Banakhar and Hassouna39 evaluated sensitivity, specificity, and predictive values for a staged implant versus PNE. For PNE, positive and negative predictive values were 99% and 82.1%, respectively, and for staged test were 90% and 92.9%, respectively.39 This study showed that PNE has a high positive predictive value which, in conjunction with the potential of a simple office-based procedure, may be preferable for certain patients. Although the staged procedure may be more costly and require two OR visits, it has the advantage of a higher conversion rate to implant and potential for a longer trial period. The decision for PNE versus staged procedure should be individualized for each patient and practice model. Preoperatively, patients should be counseled regarding procedure risks including infection, implant site or leg pain, and potential need for revision or reprogramming.4
increased progression to implant placement with staged procedure versus PNE (88% vs. 46%, P < .02). Banakhar and Hassouna39 evaluated sensitivity, specificity, and predictive values for a staged implant versus PNE. For PNE, positive and negative predictive values were 99% and 82.1%, respectively, and for staged test were 90% and 92.9%, respectively.39 This study showed that PNE has a high positive predictive value which, in conjunction with the potential of a simple office-based procedure, may be preferable for certain patients. Although the staged procedure may be more costly and require two OR visits, it has the advantage of a higher conversion rate to implant and potential for a longer trial period. The decision for PNE versus staged procedure should be individualized for each patient and practice model. Preoperatively, patients should be counseled regarding procedure risks including infection, implant site or leg pain, and potential need for revision or reprogramming.4
 FIGURE 17.5 Passing lead introducer with radiolucent marker halfway through the sacral plate. (Courtesy of Axonics, Inc.) |
 FIGURE 17.6 Placement of quadripolar lead wire along S3 nerve with curved stylet. A: AP view. B: Lateral view. |
Routine use of intraoperative fluoroscopy is recommended for staged lead positioning in order to optimize lead placement. Both AP and lateral fluoroscopy views should be used to assess needle and final tined lead wire placement. The ideal lead placement in the AP view is shown with the trajectory of the lead curving out from medial to lateral, and on the lateral view having a gentle curvature from cephalad to caudad (Fig. 17.6). Proper lead placement can be confirmed by appropriate sensory and motor responses (Table 17.1). Achieving bellows response before toe flexion at ≤2 mA on all four electrodes is considered ideal.4
TABLE 17.1 Sacral Nerve Sensory and Motor Responses | ||||||||||||||||||||||
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