Philip E. V. van Kerrebroeck1 and Martijn A. C. Smits1
Department of Urology, Maastricht University Medical Centre, P. Debyelaan 25, Maastricht, 6229 HX, The Netherlands
Philip E. V. van Kerrebroeck
Sacral neurostimulation (SNS) is a minimally invasive treatment option for symptoms of overactive bladder (OAB) when non-invasive therapies such as behavioural modification, pelvic floor rehabilitation and pharmacological therapy have failed. The efficacy of SNS in patients with idiopathic OAB has been shown in clinical trials, with a reported long-term success rate of approximately 70 % and a 5-year patient satisfaction of up to 90 %. The largest systematic review evaluating SNS for neurogenic lower urinary tract dysfunction calculated an overall success rate of 68 %. It follows from these data that in spite of its potential, SNS still offers no solution to the problems of a considerable number of patients with symptoms of (neurogenic) OAB.
Sacral neurostimulation (SNS) is a minimally invasive treatment option for symptoms of overactive bladder (OAB) when non-invasive therapies such as behavioural modification, pelvic floor rehabilitation and pharmacological therapy have failed. The efficacy of SNS in patients with idiopathic OAB has been shown in clinical trials, with a reported long-term success rate of approximately 70 % [1, 2] and a 5-year patient satisfaction of up to 90 % . The largest systematic review evaluating SNS for neurogenic lower urinary tract dysfunction calculated an overall success rate of 68 % . It follows from these data that in spite of its potential, SNS still offers no solution to the problems of a considerable number of patients with symptoms of (neurogenic) OAB.
Sacral neuromodulation consists of implantation of a tined electrode in the S3 sacral foramen with subsequent connection to an implantable pulse generator. The working mechanism of SNS is unclear, but it is indicated that electrical stimulation of the S3 sacral nerve root leads to modulation of the afferent signals and micturition reflex pathways in the central nervous system . One limitation of the selection of S3 is that only one of the pathways inducing the inhibitory reflex is stimulated.
The pudendal nerve (PN) originates from S2, S3 and S4 sacral nerve roots. Therefore selection of the pudendal nerve, as a site for stimulation, provides afferent stimulation of S2, S3 and S4 nerve roots. Since more afferents are stimulated with direct pudendal nerve stimulation (PNS) than with SNS, chronic PNS may be an alternative option in patients in whom SNS fails .
The Pudendal Nerve
The pudendal nerve (PN) is a peripheral nerve, and consists mainly of afferent sensory fibres from sacral nerve roots S1, S2 and S3. Human cadaveric studies have shown that 50 % of the pudendal nerves contain nerve fibres originating from the roots S2, S3 and S4, 40 % only from S2 and S3 and 10 % from S3 and S4 only . Consequently, the PN is a major contributor to bladder afferent regulation and hence bladder function. Pudendal nerve entrapment often leads to significant voiding dysfunction, including urinary incontinence and detrusor overactivity [8–10].
Anatomy of the Pudendal Nerve
The PN originates in the sacral plexus and derives its fibres from the ventral rami of second, third and fourth sacral nerves (S2, S3 and S4). The nerve also gets contributions from the adjacent roots of S1 and S5 . The pudendal nerve roots emerge from the anterior sacral foramina containing both somatic and autonomic fibres. The PN together with the internal pudendal artery exits the pelvis through the greater sciatic foramen, travelling anterior to the piriformis muscle and posterior to the coccygeal muscle and the sacrospinous ligament. At this point the PN winds posteriorly around the ischial spine, medial to the pudendal vessels and deep to the sacrotuberous ligament in the biligamentary tunnel. It swings anteriorly through the lesser sciatic foramen and the Alcock’s canal to enter the perineum. Here the PN terminally branches into the dorsal genital nerve (DGN), the inferior rectal nerve and the perineal nerve [7, 11]. The DGN eventually runs through the suspensory ligament to the dorsum of the penis or clitoris. The inferior rectal nerve extends motor branches to the levator ani muscle and the external anal sphincter, and sensory branches to the perianal region and the scrotum. Alongside these branches to the scrotum runs the scrotal branch of the perineal nerve into the common scrotal branch, which innervates the scrotal skin. The other branches of the perineal nerve, the bulbocavernosus branch and the medial urethral sphincter branch, run down to the striated urethral sphincter [11, 12].
Pudendal Nerve Stimulation
Stimulation of nerve fibres can be achieved by implanting an electrode close to the nerve. The initial nerve localisation and implanting techniques used were initially complex and have recently been replaced by minimally invasive, percutaneous approaches. The percutaneous procedures can be performed with use of the quadripolar tined lead that is also used for SNS, connected to an implantable pulse generator. Using the combination of this tined lead and an implantable pulse generator gives the opportunity for a staged implant procedure. During the first stage the lead is implanted adjacent to the PN and connected to external stimulator. If during the testing period the stimulation is successful, the second stage consists of implanting an implantable pulse generator.
An alternative to this ‘electrode’ system is a lead-less mini-neurostimulator with integrated electrodes, which can be implanted at its target location (Alcock’s canal) .
Surgical Access to the Pudendal Nerve
The anatomy of the PN and its branches enables the implantation of an electrode at several sites. At the ischial spine, the PN is a relatively isolated structure and stimulation at this site theoretically diminishes the risk of unwanted activation of S2 motor fibres to sciatic nerve . The PN can be accessed percutaneously for stimulation at the ischial spine by a posterior or perineal approach for insertion of the electrode. With the perineal approach the PN can also be reached at the Alcock’s canal .
When implanting an electrode by the posterior approach at the ischial spine, the ischial spine can be located by palpating the lower margin of the sacrotuberous ligament where it forms an angle with the ischial tuberosity [14–16]. The electrode can also be inserted perpendicularly at the intersection of a horizontal line from the greater trochanter and a vertical line from the ischial tuberosity tip (using fluoroscopy) [13, 14].
The perineal approach is performed by insertion of the electrode perpendicularly to the perineum between the ischial tuberosity and the anus. A finger is placed into the rectum or the vagina to prevent puncturing the bowel or vagina and then used to guide the needle to the ischial spine or Alcock’s canal [6, 17, 18].
EMG Recordings for Ensuring Correct Electrode Placement
Since the outcome of PNS depends on the proximity of the electrode to the nerve , it has been suggested at the time of the development of the percutaneous placement techniques that placement of the electrode needs electrophysiological confirmation. Anal sphincter electromyography (EMG) and measurement of amplitude and latency during acute stimulation have been used . In practice, the positioning of the electrode based on EMG recordings appears to be difficult. A recent study combining clinical results with cadaver studies has shown that the electrode can also be positioned satisfactorily without EMG confirmation. The authors conclude that lead placement can be based on evidence of visible and palpable sphincter contraction .
Dorsal Genital Nerve Stimulation
As an alternative method to direct stimulation of the PN, stimulation of nerve branches originating from the PN can be used. For this purpose, the DGN has been used as a peripheral stimulation site of the PN. The DGN can be accessed either using surface electrodes, as part of the DGN is localised superficially to the skin outside the pelvis, or with an electrode inserted more proximal along the tract of the DGN. In addition to using sensory function of the nerve to locate the stimulus in the glans penis or the clitoris, electrodes can be positioned near the DGN using the genito-anal reflex .
Mechanism of Action
Stimulation of the PN is different from SNS, as it provides afferent stimulation not only of the S3 sacral nerve root but also of the S2 and S4 roots. Both forms of stimulation, however, seem to rely on the same neurophysiological mechanisms. The working mechanism of stimulation of sacral nerve roots is not fully understood. In OAB, neurostimulation is supposed to act by inhibiting bladder afferent activity through its action on somatic afferent pathways, and hence blocking abnormal sensory input to spinal cord and brain. Neurostimulation may also block interneuron transmission of bladder sensory input and can directly inhibit bladder preganglionic neurons of bladder efferent pathways as well [5, 21].
The modulatory effects of PNS have been studied in normal and spinal animals, and important aspects of the spinal mechanism of action have been identified. These mechanisms rely on spinal interaction between somatic afferent fibres of the pudendal nerve and autonomic pathways controlling the bladder and bladder neck [22–26]. Projection of pudendal pathways into spinal sympathetic and sacral parasympathetic systems has been found in several animal experiments but also in humans [27–29].
The number of published studies and the experience with PNS are limited compared to SNS. In SNS, in a single blinded crossover trial 30 patients randomly received a test with SNS and PNS (both tined quadripolar lead) by the perineal approach for OAB and urinary retention (10 %). The overall reduction in symptoms was 63 % for PNS and 46 % for SNS. PNS was chosen as a superior lead in 79.2 % of patients . Another study evaluating the success of PNS with a percutaneous nerve evaluation test included 14 female patients with idiopathic OAB. Six patients (42 %) responded positively (>50 % improvement in urodynamic parameters) and received permanent PNS with a lead-less mini-neurostimulator . One of the first relevant clinical studies on the effect of PNS with use of intermittent (weekly) needle stimulation was performed in a heterogeneous group of patients with idiopathic and neurogenic detrusor overactivity (n = 29). These authors succeeded in showing a significant increase in functional bladder capacity in all patients and a 30 % decrease of frequency in 11 patients . There is only one other study that has evaluated the effect of PNS in patients with neurogenic OAB. In this study test stimulation has been performed with a tined quadripolar lead in 15 patients. Eight patients regained continence during the test phase and two patients improved by more than 88 %. Two patients reduced the number of incontinence episodes by 50 % and three patients had no improvement .
Clinical Experience with DGN
Studies using stimulation of the DGN have been performed in acute and experimental settings, without long-term chronic trials. Only one larger study using continuous stimulation during 1 week is available. Of 21 female patients with urgency incontinence 55 % showed an increase in cystometric capacity and 47 % experienced a greater than 50 % reduction in incontinence episodes .
As with SNS, the effect of PNS has also been evaluated for other (urological) indications. In a small (21 patients) prospective, single blind, randomised crossover trial of SNS versus PNS for bladder pain syndrome, 77 % of patients had a significant improvement in the outcome of pain questionnaires and received a permanent implant. PNS was chosen as the better method of stimulation in 77 % . In one study the effect of PNS on non-obstructive urinary retention was evaluated in three patients as part of a study mixed with patients suffering from OAB . Faecal incontinence is currently being evaluated as a novel indication for PNS. One study showed a success rate of 70 %, considering a more than 50 % symptom reduction as success . This indicates that patients suffering from OAB in combination with faecal incontinence, not responding to SNS for both problems, could be candidates for PNS.
PNS is considered an interesting alternative form of electrical stimulation for the treatment of OAB when non-invasive therapies have failed. As the pudendal nerve (PN) contains afferent fibres of S2, S3 and S4 nerve roots, more afferents are stimulated with PNS than with sacral nerve stimulation (SNS), and therefore may be an alternative option in patients in whom SNS fails. Anatomically the PN can be approached in different ways and clinical research indicates better overall results with PNS than with SNS. However only a limited number of permanent implantations have been performed and long-term results are lacking. Therefore further research has to clarify the exact place of PNS in the treatment of lower urinary tract dysfunction.
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