History of sacral nerve stimulation

M. H. Saxtorph, a Danish general surgeon, introduced the idea of electrical stimulation for the treatment of bladder dysfunction in 1878. Since that time multiple iterations of bladder, spinal cord, pelvic and pudendal nerve, and pelvic floor electrical stimulation techniques have been introduced. Nashold and Jonas demonstrated direct spinal cord stimulation facilitated micturition. However, their work was met with suboptimal outcomes because of concomitant stimulation and contraction of the external urethral sphincter resulting in high outlet resistance. To overcome the problem of simultaneous stimulation of the detrusor and striated urethral sphincter, investigators sought more peripheral targets. As early as 1979, Tanagho and his group performed multiple experiments using a canine model, and determined that stimulation of the ventral portion of the sacral nerve root was most effective in achieving micturition. The finding that a detrusor contraction could be achieved separately from activation of the urethral sphincter allowed them to forsee a feasible electronic “bladder pacemaker” for use in humans. This landmark research, ultimately lead to the technique for sacral nerve stimulation and initiation of clinical trials.

Mechanism of action

Although the exact mechanism of action of SNS in the treatment of voiding and bowel dysfunction is not completely understood, we have gained more insight into the processes at work. One common question is: how does a single intervention remedy both storage and emptying disorders? Addressing this requires an understanding of normal voiding patterns.

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, on reaching the pontine micturition center, simultaneously allows for a coordinated detrusor contraction and concomitant urethral relaxation, thus facilitating urination. 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. 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.

Urgency-frequency and urge incontinence fall under the umbrella term of overactive bladder (OAB). A recent study estimated that one-third of American adults suffer from bothersome symptoms of OAB, and that prevalence increases with age. Most cases of OAB are considered to be idiopathic, however, animal data exist suggesting there may be improper signaling from the bladder urothelium leading to subsequent voiding dysfunction.

Extensive work to help understand the neurophysiology of voiding reflexes has been accomplished by deGroat and colleagues. They demonstrated that sacral preganglionic outflow to the bladder receives inhibitory input from both somatic and visceral afferents. deGroat et al also showed that stimulation of the somatic afferents in the pudendal nerve induces inhibitory mechanisms. This is supported by the finding that interneurons in the sacral autonomic nucleus exhibit firing during bladder activity and are inhibited by stimulation from somatic afferents.

Because of the low level of stimulation delivered with SNS, it most likely functions via the somatic afferents because these nerves are depolarized at much lower levels than the autonomic nerves. For patients with urinary retention, SNS is believed to activate the pudendal nerve afferents originating from the pelvic organs into the spinal cord. At the level of the spinal cord, pudendal afferents may turn on voiding reflexes by suppressing exaggerated guarding reflexes, thus relieving symptoms of patients with urinary retention. In patients with OAB, it is theorized that these same pudendal afferents can activate the inhibitory reflexes that promote bladder storage by inhibiting the afferent limb of an abnormal voiding reflex. This blocks input to the pontine micturition center, thereby restricting involuntary detrusor contractions without interfering with normal voiding patterns. Research comparing the positron emission tomography (PET) scans of urge incontinent individuals with long-term SNS use to those who had activation of stimulation for the first time in the PET scanner found notable differences. In the group with SNS for at least 6 months, blood flow to areas involved in sensorimotor learning was decreased, suggesting that SNS influences brain areas involved in bladder alertness and awareness.

In patients with fecal incontinence, limited information is available to explain the mechanism of action. A small study demonstrated the use of SNS was associated with higher tolerance of rectal distention, but the neurologic mechanism behind this is unclear. Similar to their action in the urinary system, the pudendal afferent somatic fibers are believed to be the primary player, working by inhibiting colonic propulsive activity and activating the internal anal sphincter. A mechanism relating to colonic motility may explain why patients with significant anal sphincter defects may still derive benefit from SNS. Notably, chronic constipation is also an approved indication for Interstim in Europe. Dinning and colleagues have demonstrated increased colonic peristalsis and frequency of bowel movements in slow-transit constipation participants with SNS stimulation. As with the bladder, we are faced with the complexity of understanding how SNS may be effective against abnormalities in both bowel storage and emptying.

Mechanism of action

Although the exact mechanism of action of SNS in the treatment of voiding and bowel dysfunction is not completely understood, we have gained more insight into the processes at work. One common question is: how does a single intervention remedy both storage and emptying disorders? Addressing this requires an understanding of normal voiding patterns.

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, on reaching the pontine micturition center, simultaneously allows for a coordinated detrusor contraction and concomitant urethral relaxation, thus facilitating urination. 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. 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.

Urgency-frequency and urge incontinence fall under the umbrella term of overactive bladder (OAB). A recent study estimated that one-third of American adults suffer from bothersome symptoms of OAB, and that prevalence increases with age. Most cases of OAB are considered to be idiopathic, however, animal data exist suggesting there may be improper signaling from the bladder urothelium leading to subsequent voiding dysfunction.

Extensive work to help understand the neurophysiology of voiding reflexes has been accomplished by deGroat and colleagues. They demonstrated that sacral preganglionic outflow to the bladder receives inhibitory input from both somatic and visceral afferents. deGroat et al also showed that stimulation of the somatic afferents in the pudendal nerve induces inhibitory mechanisms. This is supported by the finding that interneurons in the sacral autonomic nucleus exhibit firing during bladder activity and are inhibited by stimulation from somatic afferents.

Because of the low level of stimulation delivered with SNS, it most likely functions via the somatic afferents because these nerves are depolarized at much lower levels than the autonomic nerves. For patients with urinary retention, SNS is believed to activate the pudendal nerve afferents originating from the pelvic organs into the spinal cord. At the level of the spinal cord, pudendal afferents may turn on voiding reflexes by suppressing exaggerated guarding reflexes, thus relieving symptoms of patients with urinary retention. In patients with OAB, it is theorized that these same pudendal afferents can activate the inhibitory reflexes that promote bladder storage by inhibiting the afferent limb of an abnormal voiding reflex. This blocks input to the pontine micturition center, thereby restricting involuntary detrusor contractions without interfering with normal voiding patterns. Research comparing the positron emission tomography (PET) scans of urge incontinent individuals with long-term SNS use to those who had activation of stimulation for the first time in the PET scanner found notable differences. In the group with SNS for at least 6 months, blood flow to areas involved in sensorimotor learning was decreased, suggesting that SNS influences brain areas involved in bladder alertness and awareness.

In patients with fecal incontinence, limited information is available to explain the mechanism of action. A small study demonstrated the use of SNS was associated with higher tolerance of rectal distention, but the neurologic mechanism behind this is unclear. Similar to their action in the urinary system, the pudendal afferent somatic fibers are believed to be the primary player, working by inhibiting colonic propulsive activity and activating the internal anal sphincter. A mechanism relating to colonic motility may explain why patients with significant anal sphincter defects may still derive benefit from SNS. Notably, chronic constipation is also an approved indication for Interstim in Europe. Dinning and colleagues have demonstrated increased colonic peristalsis and frequency of bowel movements in slow-transit constipation participants with SNS stimulation. As with the bladder, we are faced with the complexity of understanding how SNS may be effective against abnormalities in both bowel storage and emptying.

Procedure

SNS involves a 2-stage procedure. The initial phase is considered the test stimulation period where the patient is allowed to evaluate whether the therapy is effective. There are 2 techniques that exist to perform the test stimulation.

• 1.
  

  The first is an office-based procedure termed the percutaneous nerve evaluation (PNE). This involves placing a temporary electrode wire through the S3 sacral foramen under local anesthesia, with or without fluoroscopic guidance. The wire is connected to an external generator worn for a trial period of 3-7 days ( Figures 1 and 2 ). Those with at least 50% improvement in symptoms during the test phase are candidates for chronic implant of the lead and implantable pulse generator (IPG). The advantage of the PNE is that it is an incision free procedure performed in the office using local anesthesia. The disadvantage is that the wire is not securely anchored in place and has the propensity to migrate away from the nerve with physical activity.

  
  

  
  

  
  

  

  
  

  
  

  Proper placement of needle at the S3 foramen

  
  

  Optimal placement of the needle is at approximately a 60 degree angle, into the medial and superior portion of the S3 foramen.

  
  

  Reprinted, with permission, from Medtronic, Inc.

  
  

  
  

  
  

  

  
  

  
  

  Components of Interstim SNS system during trial period

  
  

  During the trial period, the device consists of the chronic lead wire connected to the temporary wire extension in the future site of the implantable pulse generator should the trial be deemed successful. The temporary wire exits the skin to connect to the stimulator box. InterStim; Medtronic Inc, Minneapolis, MN.

  
  

  SNS , sacral nerve stimulation.

  
  

  Reprinted, with permission, from Medtronic, Inc.

  
  
  
  
• 2.
  

  The second option is a staged implant introduced by Spinelli in 2003 that is typically performed as an outpatient procedure using local anesthesia, intravenous sedation, and intraoperative fluoroscopy ( Figure 3 ). This procedure involves placement of the chronic quadripolar lead wire adjacent to a sacral nerve root (typically S3). The lead is self-anchoring and therefore reduces the potential for migration. The patient goes through a test phase for 7-14 days. The advantage of this technique is that it allows for a longer trial period with minimal risk of lead migration. The chronic wire also has 4 electrodes, each of which can be trialed as the active electrode to achieve optimal outcomes. During the second stage, or final implant, the previously placed tined-lead remains in place and is simply connected to the IPG. This eliminates the chance of variable lead placement between the test and implantation phases. The disadvantage of the staged implant is that it requires 2 visits to the operating room and may be more costly to the health care system. However, in a prospective study comparing the PNE with the staged implant, there was a significantly higher rate of conversion to implant with the staged procedure vs the PNE (88% vs 46%).

  
  

  
  

  
  

  
  

  
  

  Proper placement of quadripolar lead wire through the S3 foramen

  
  

  The most proximal of the 4 electrodes is seen just anterior to the sacrum.

  
  

  Noblett. Sacral nerve stimulation review. Am J Obstet Gynecol 2014 .

  
  

To determine optimal lead placement, both motor and sensory responses are desired. The typical sensory response is a tapping or vibratory sensation in the vagina, rectum, or perineum. The motor response includes a pulling in of the pelvic floor muscles known as a “bellows” response, and/or flexion of the great toe. There has been no definitive study to determine which factor is more predictive of success. One small, prospective study did report that a positive motor response was more predictive than a sensory response in achieving a successful trial stimulation. A larger retrospective analysis reported both to be highly predictive. Recent investigation comparing patients evaluated with both sensory and motor response to those evaluated with motor response alone demonstrated similar rates of successful trial stimulation and device explant between groups with 4-year follow-up. Although these findings may suggest that motor response alone may be adequate, the best predictor of a successful response is still not known, and many surgeons prefer to have both motor and sensory as guides for optimal placement.

The most common nerve targeted for stimulation is the S3 nerve root. Benson et al, through electrodiagnostic techniques, demonstrated that the third sacral nerve root provided the majority of innervation to the pelvic organs of interest. However, the sacral anatomy is extremely variable and thus occasionally the S4 or S2 nerve roots are stimulated.