Electrical stimulation of the sacral nerves as a treatment for the symptoms of lower urinary tract dysfunction (LUTD) dates back to the mid-1990s, when sacral nerve stimulation (SNS), an alternative term for sacral neuromodulation (SNM), received approval from the US Food and Drug Administration (Marcelissen et al, 2011).
The work of Tanagho and Schmidt (1982) first demonstrated the therapeutic potential of SNS in the early 1980s (Van Kerrebroeck and Marcelissen, 2012). During the past two decades, SNS has been adapted and refined, both in terms of the implantation techniques and the device electronics. SNM leads are now implanted percutaneously and some devices are both safe during magnetic resonance imaging (MRI) and rechargeable.
SNM can be used to treat two LUTD conditions: overactive bladder (OAB) syndrome and female non-obstructive chronic urinary retention (FCUR) (National Institute for Health and Care Excellence (NICE), 2015; Liberman et al, 2017; NICE, 2019).
SNM therapy is also an option for faecal incontinence and constipation and is used by colorectal surgeons (Jones et al, 2016).
Background
SNM is believed to work by electrically stimulating the S3 and/or S4 sacral spinal nerves (Mitchell et al, 2011). Exactly how this produces a decrease in bladder symptoms in humans is not fully understood, but it is likely to involve a complex series of neural interactions (Liberman et al, 2017). Numerous studies have identified that stimulation of the sacral nervous system produces interactions that can both suppress some nerve functions yet simultaneously stimulate other parts into a reaction (Jones et al, 2016).
The stimulation of the sacral spinal nerves that control the bladder and sphincter is accomplished by the placing of an electrode (a tined lead, which allows it to anchor to the body tissue) through the S3 foramen, connecting it to an implantable pulse generator (IPG), the power source for the stimulation. The IPG is implanted under the skin, usually in the buttock.
SNM is an expensive treatment, with the permanent device and implantation costing around £10 000. It is important that patients are carefully selected for this form of treatment.
Overactive bladder
Overactive bladder (OAB) is a common condition that is thought to affect many millions of people throughout the world (Bartley et al, 2013). It has been estimated to affect around 16% of men and 17% of women (Sukhu et al, 2016). However, many people affected by OAB never seek help with their symptoms, making it difficult to understand its true prevalence. OAB syndrome is the name given to a group of symptoms that include urgency, frequency of urination, nocturia and urge incontinence. The underlying cause of OAB is detrusor (bladder muscle) overactivity (Sukhu et al, 2016). The International Continence Society (ICS) defines OAB as urinary urgency, with or without urge incontinence, which highlights that not all OAB patients are incontinent of urine (ICS, 2018). These symptoms affect a patient's lifestyle and have a debilitating effect on quality of life.
NICE has published guidance for the treatment of female urinary incontinence, including a treatment management pathway for OAB (NICE, 2015; 2019). The first-line treatment for OAB is bladder training and education on fluid management. The second-line therapy is the use of a pharmacological interventions in the form of antimuscarinic medications such as oxybutynin, solifenacin or tolterodine, for example. Another pharmacological option is mirabegron, a beta-3 agonist, which is normally offered after an antimuscarinic drug has failed to resolve symptoms (Hashim et al, 2015). Antimuscarinics can be successful in treating OAB, but often their side effect profile of dry mouth, dry eyes, headaches and dizziness can limit their usefulness (Olivera et al, 2016). At least two of the pharmacological options should be tried before progressing to the third-line treatment of surgical intervention. However, the European Association of Urology's (2018) incontinence guidelines caution against the long-term use of antimuscarinics, owing to their link with an increased risk of impairment of cognitive function, especially in older people (Coupland et al, 2019). Surgical interventions include the use of botulinum toxin type A (commonly referred to by the trade name Botox) injections into the muscle of the bladder detrusor muscle, SNM, bladder augmentation (this is also known as clam cystoplasty) or urinary diversion. These first two interventions, Botox and SNM, are minimal interventions when compared with the more major and life-changing surgery of clam cystoplasty or urinary diversion and the formation of a urostomy.
SNM or intradetrusor Botox?
SNM and intradetrusor Botox for the treatment of OAB have been found to be comparable in their success rate and cost effectiveness. However, the ROSETTA trial, which compared both treatments, reported that Botox patients gave their treatment a higher satisfaction rate (Amundsen et al, 2018). Almost all urological centres in the UK will offer intradetrusor Botox as a treatment for OAB, but only a small number offer the option of SNM. This tends to result in OAB patients being steered towards choosing intradetrusor Botox and can mean some patients are offered SNM as an option following failed Botox treatment. In some cases, intradetrusor Botox is too effective in paralysing the bladder, which causes urine retention or an inability to empty the bladder sufficiently. This is a factor for some patients when presented with this treatment option (Chen, 2010). Some patients cannot contemplate or physically undertake self-catheterisation.
The relative costs of Botox and SNM over a 5-year period have been comparable in the past as Botox injections need to be repeated every 6 to 9 months (Leong et al, 2011a). However, as more centres have progressed to delivering Botox injections under local anaesthetic via flexible cystoscopy in outpatient department settings, this has greatly reduced the cost of delivery by removing the procedure from the expensive-to-run operating theatre setting, on which original comparisons were made (Leong et al, 2011a). In the COVID-19 era there may be advantages to SNM over Botox since SNM does not generally require repeated attendance at the hospital and the very latest SNM devices are programmable over a telephone link.
Female non-obstructive chronic urinary retention
FCUR is a complicated condition and often young women with an established inability to void have complex psychosocial issues. Many of these patients are said to have Fowler's syndrome (Fowler et al, 1985), named after Professor Clare Fowler of the National Hospital for Neurology and Neurosurgery in London, who first described the condition back in 1985 (Elneil, 2010). However, this term may be too readily applied to many young women with urinary retention. Fowler's syndrome may only account for voiding difficulties in a small proportion of the young women with urinary retention (Tawadros et al, 2015). Fowler's syndrome is not easy to diagnose since there is no single test that establishes the diagnosis.
The profile of these patients is young women who go into sudden urinary retention without any clear pathological or anatomical reason (Liberman et al, 2017). What is noted in these patients is an excessively painful catheterisation experience when used to relieve their urinary retention. This limits the option to teach these patients to perform clean intermittent self-catheterisation (CISC) to manage their situation. These patients often describe a gripping sensation as the catheter is passed (Elneil, 2010). This is believed to be caused by the inability of the external urinary sphincter to relax, not allowing micturition and making the catheterisation painful (Elneil, 2010). The ‘overactive’ sphincter activity in Fowler's syndrome may have a secondary inhibitory effect on the bladder muscle (Elneil, 2010). In some cases, the retention in these patients seems to be precipitated by general anaesthesia and some form of pelvic surgery or having had a degree of emotional or psychological stress in their life (Van Kerrebroeck and Marcelissen, 2012).
The use of SNM as a treatment for FCUR gives this group of patients another option other than the use of some form of catheterisation. Most of these patients are young—in their late teens or mid-twenties—when they present in painless retention. As with the OAB patients, the next line of treatment options are major surgical interventions such as supra-pubic catheterisation, the Mitrofanoff procedure or even urinary diversion should catheterisation or SNM not be suitable treatments (Elneil et al, 2014). However, given the difficulty of diagnosis and the complex psychosocial aspects of this condition, such surgical interventions are best avoided.
SNM trial phase
The process of assessing a patient's suitability for treatment with SNM begins with a trial. There are two trial options:
All antimuscarinics and beta-3 agonist (mirabegron) medication must be stopped prior to implantation to remove any doubt about the outcome of the trial (Siegel et al, 2015).
PNE versus an advanced trial
The PNE lead can be sited under local or general anaesthesia, with the trial phase lasting 7 to 10 days and a bladder diary used to record the effects on urinary symptoms for assessment.
Following this trial period, the leads are easily removed in the clinic, using simple traction, with little discomfort felt by the patient. Patients in whom the trial has been successful are listed for insertion of a permanent SNM device.
The advanced trial patients have a tined lead sited either under local or general anaesthesia, usually with some additional sedation if under local anaesthesia. These patients are assessed at week 2 and week 4 of the trial. Following this, the successful advanced trial patients are converted to a full permanent SNM implantation by connecting an internal pulse generator (IPG), which is surgically placed subcutaneously into the buttock region, to the already implanted tined lead. For those who are unfortunately unsuccessful during the trial, the tined lead is surgically removed.
Both these procedures are either performed under general anaesthesia or local anaesthesia/sedation. The choice of which method of trial is dependent on individual centres, which must weigh up the issues of the cost of the more expensive advanced trial, and the availability of potential extra theatre time that may be required, against the fact that is it more reliable than the PNE trial because of the higher-quality construction of the tined lead (Leong et al, 2011b).
Motor verses sensory response
The choice of local anaesthesia, with or without sedation, or general anaesthesia, affects the method of assessing the placement of the lead. When siting the lead under local anaesthesia, the clinician relies on the patient describing the sensory response to stimulation, helping to guide the placement of the lead through their description of the location of the sensation (Peters et al, 2011). Under general anaesthesia, a motor response is used, where an anal bellows and a flexing of the big toe are used to assess the correct location of the lead under stimulation (Rice and Paquette, 2017). This occurs due to stimulation of the S2–S3 nerves, which control the rectal and urinary sphincter muscles as well as causing the big toe to flex. Studies have shown that both methods of lead placement are of similar efficacy, with no noticeable difference between sensory or motor response as a guide to siting leads and the success rates (Mitchell et al, 2011; Prapasrivorakul et al, 2014). This potentially allows the choice of anaesthetic to be discussed between patients and clinicians.
Evaluation of the trial
The trial period is usually in the order of 7 to 14 days for a PNE trial, with a review at the conclusion of this period, and 4 weeks for the advanced trial, with a review 2 weeks into this period. The benchmark for success is generally taken to be a 50% improvement in urinary symptoms (Elneil et al, 2014; Peeters et al, 2014). This is assessed by comparing bladder diaries, records of voided volumes, frequency of voids and any episode of incontinence. In FCUR a patient's requirement to self-catheterise during the trial period is monitored. The information before and during the SNM trial allows for comparison and a decision can be made about proceeding to a permanent SNM device. It is important to take into consideration the patient's perspective on how the trial has affected their LUTD. A small reduction in urinary frequency or the need for self-catheterisation may be regarded by some patients as a great success but other patients may be less impressed. The bladder diary will not always capture the effect on urgency, for example.
Evidence suggests that between 50% and 70% of patients experience an improvement in their OAB symptoms, dependent on which trial method is used, and in FCUR 64% to 86% experience an improvement (Leong et al, 2011b; Elneil et al, 2014).
In the author's experience, a complete resolution in symptoms with SNM is rare. This may seem disappointing, but it should be remembered that patients undergoing SNM are a difficult group to treat and their symptoms have already proved resistant to first- and second-line treatments.
Implantation of the permanent device
The position of the permanent device can be seen in Figure 1. The procedure for implanting a permanent SNM device depends upon the nature of the trial undertaken. If PNE was used to assess suitability then a full implantation will be undertaken. When siting the tined lead, fluoroscopy X-ray is used to ensure the optimum depth of lead implantation. Patients who have progressed through an advanced trial already have a tined lead in position so only require the connection and implantation of the IPG. For the PNE patients, the tined lead and IPG will be sited in one procedure.
The choice of which side of the body the IPG is implanted is dependent on the response to stimulation. In general IPG is positioned on the patient's dominant hand side, since this makes it easier for the patient to use the hand-held controller. The controller allows the patient to communicate with their implant. This is achieved by placing the controller directly over the battery site, thus communicating with the IPG through the skin, allowing the patient to make some limited adjustments to the settings. For most patients this manoeuvre is easier with the dominant hand. These adjustments can sometimes improve programmed settings and the ability to void (for FCUR patients) or reduce the strong sensation to void or an incontinence episode (OAB patients). As with the trial phase, the implantation can be undertaken under general anaesthesia or local anaesthesia/sedation and is dependent on the individual centre's preference, patient choice and comorbidities.
Follow up and management
A patient implanted with a permanent SNM device either has their device switched on and programmed at the time of implantation or, in some centres, they are seen 2 weeks postoperatively in clinic. During the consultation, with a nurse, clinical scientist, technician or other allied health professional, their device is switched on and programmed. Dependent on the make of the device, there may be multiple programs for the patient to try and they can select the best one for their symptoms. The patient will receive education on their patient controller that enables them to adjust or switch programs as applicable. Importantly, patient are informed that they can switch off the IPG completely should there be an issue with pain or when going through airport security scanners, for example, as this theoretically could affect the device. Patients are given safety advice regarding certain activities they should avoid to reduce risk of damage to their implant. These include skiing, water skiing, trampolining, mountain biking and horse riding as there is a risk of lead fracture from these activities.
Patients are then seen annually but are given details on who to contact should any issues arise. For some patients, these may be issues with their device or lead that require further surgery to replace the damaged component, or they may feel that there has been a change in their symptoms. Reassurance can be all patients require at times.
SNM is not licensed for use during pregnancy so patients should be advised to switch off the IPG during this time and restart the therapy after the birth.
Overall SNM is a relatively safe treatment with the author's implanting centre recording no serious incidents or complications in 20 years of implanting.
Recent and future developments
For many years, the only SNM devices available were from Medtronic, which has provided devices for more than 20 years. The InterStim II model was introduced in 2005. This was a reduced-size IPG with an average lifespan of approximately 5 years and which will then need to be replaced, requiring surgery and the incurred cost of a new IPG at around £7000. In the past 2 years, Axonics has entered the market, bringing competition with a smaller rechargeable IPG that, with its lead, also allows for a greater ability for patients to undergo MRI scanning if required for any other health issue. The InterStim II device has greater limits on its MRI compatibility due to its lead technology, which is restricted to head and neck MRI scans only. However, Medtronic has recently introduced a smaller rechargeable device, the InterStim Micro, which was unveiled in January 2020. This has a similar MRI status to the Axonics device. Medtronic has also developed a new lead for the InterStim II to enable it to have greater MRI compatibility.
These developments herald a new era for patient choice in this area. The rechargeable devices offer the potential for fewer surgical procedures as both companies claim a 15-year lifespan for their respective IPGs. However, some patients still prefer the InterStim II option, which requires less input from them as opposed to the rechargeable option, which requires the patient to attach a recharging device over their implanted IPG once a week for approximately 1 hour to keep it operational.
Summary
SNM treatment can provide life-changing improvements for patients who have suffered years of intractable OAB symptoms or urinary retention. SNM is generally very safe and completely reversible, unlike the major surgical options of clam cystoplasty or urinary diversion. SNM should be offered to patients with resistant OAB symptoms who may be considering a urinary diversion or cystoplasty. Young women with chronic urinary retention are often difficult to diagnose and manage but SNM may be an option in well-selected patients. An improvement in quality of life can be delivered by this treatment but caution must be applied in advertising this as a cure for the patient. It should be seen as a method to improve or reduce the patient's symptoms. Before arriving at SNM as a treatment these patients will have endured a journey of assessments and failed treatments, therefore managing the patients themselves, not just their symptoms, is essential.
The new era of choice when selecting a SNM device adds greater complexity for clinicians. Should the choice of device be down to the patient, after being given the relevant information, or should the clinician lead? Time and research will tell on the advantages and disadvantages of these new developments in SNM.