Sacral neuromodulation or sacral anterior root stimulation combined with sacral deafferentation is the most well studied method of triggering bladder emptying via electrical stimulation techniques with many investigators incorporating retrospective case series or prospective pre-post study designs comprising level 4 evidence (Robinson et al. 1988; Van Kerrebroeck et al. 1996; Van Kerrebroeck et al. 1997; Egon et al. 1998; Creasey et al. 2001; Vastenholt et al. 2003; Kutzenberger et al. 2005; Kutzenberger 2007; Lombardi & Del Popolo 2009; Possover 2009). Typical participant characteristics for these studies include: detrusor overactivity; incomplete bladder emptying and frequently recurrent UTI; incontinence; and vesicoureteric reflux, refractory to conservative treatment. In each of these studies, a large percentage of subjects did become continent and were able to successfully void with these devices, whereas bladder compliance was mostly unsatisfactory with preimplantation bladder management methods. These findings appear to persist in that several reports have noted continued improvement with successful continence rates of 73-88% over an average follow-up period up to 8.6 years (Egon et al. 1998; Vastenholt et al. 2003; Kutzenberger et al. 2005; Kutzenberger 2007; Lombardi & Del Popolo 2009). Of note, Lombardi and Del Popolo (2009) conducted a study that included patients with underactive bladder (n=13) in addition to those with overactive bladder (n=11) and reported similar results for both groups (i.e., reduction in incontinence and increased voiding volume). However, 30.8% of persons in the underactive bladder group had a loss of efficacy over the follow-up period (mean of 60.7 months) as compared to none in the overactive bladder group.
Several of these investigators reported a significant decrease in UTIs among participants, even after long-term use (Van Kerrebroeck et al. 1996; Egon et al. 1998; Vastenholt et al. 2003; Creasey et al. 2001; Kutzenberger et al. 2005; Kutzenberger 2007; Martens et al. 2011) and autonomic dysreflexia (Van Kerrebroeck et al. 1996; Egon et al. 1998; Creasey et al. 2001; Kutzenberger et al. 2005; Kutzenberger 2007; Possover 2009). Some investigators performed satisfaction surveys and reported that most participants remained satisfied with the device, even after many years. In particular, Vastenholt et al. (2003) and Martens et al. (2011) gave a Qualiveen questionnaire for assessing bladder health-related QoL and impact of urinary problems. In the study by Vastenholt et al. (2003), the top three advantages noted by stimulator users was a reduction in UTIs (68% reporting), improved social life (54%) and improved continence (54%). Martens et al. (2011) reported improved QoL scores (Qualiveen and SF-36), a significantly better Specific Impact of Urinary Problems score and continence rate, in addition to reduced UTIs for patients undergoing a Brindley procedure.
Posterior rhizotomy was performed in addition to implantation of a sacral root stimulator in most reports (Creasey et al. 2001; Van Kerrebroeck et al. 1996; Egon et al. 1998; Kutzenberger et al. 2005; Kutzenberger 2007; Martens et al. 2011). The stated benefit of this deafferentation is the abolition of dyssynergia and high intravesical pressures, reduced risk of hydronephrosis and reflex incontinence. The cost is the loss of bowel reflexes and reflex erections. Nonetheless, most authors report improved bowel management in many of their patients (since the stimulator is activated during the bowel routine), and a great improvement in autonomic dysreflexia (Van Kerrebroeck et al. 1996; Egon et al. 1998; Creasey et al. 2001; Kutzenberger 2007). In the study by Robinson et al. (1988) sphincterotomies were performed on three patients with persistent reflex incontinence, and/or upper tract deterioration, while three patients were given sphincterotomies pre-implantation to prevent anticipated autonomic dysreflexia. Thus, sphincterotomy has shown some success as an option for producing some of the benefits attributed to posterior rhizotomy.
A primary purpose of posterior rhizotomy is the attainment of an areflexic bladder, thus allowing a more compliant reservoir with the potential for greater bladder capacity under lower pressure. Results from all investigations measuring capacity have shown this to be true with significant increases in bladder capacity at lower pressures associated with combined sacral anterior root stimulation and sacral deafferentation (Creasey et al. 2001; Van Kerrebroeck et al. 1996; Egon et al. 1998; Kutzenberger et al. 2005; Kutzenberger 2007). Several investigations have been conducted using different approaches aimed at conditioning the bladder with different forms of stimulation so as to achieve the same effect of increasing bladder capacity under low-pressure conditions in persons with SCI with overactive bladder and intact dorsal sacral nerves (Madersbacher et al. 1982; Kirkham et al. 2001; Kirkham et al. 2002; Bycroft et al. 2004; Hansen et al. 2005). Additionally, rhizotomy alone (without a stimulator) has shown to result in higher QoL scores over matched controls (Martens et al. 2011).
Of note, Kirkham et al. (2002) implanted the same sacral anterior root stimulator used in the majority of investigations (i.e., Finetech-Brindley stimulator) in a small group of patients (n=5) without posterior rhizotomies and therefore configured the stimulator to deliver both anterior and posterior sacral root stimulation. The conditioning posterior root stimulation was effective in producing increased bladder capacity in 3 of 5 subjects and the anterior root stimulation was able to elicit bladder emptying, but with significant residual volumes. It is important to note that the two remaining subjects sustained posterior root damage and were not included in post-operative testing. This preliminary trial suggests there is a possibility of achieving success with sacral anterior root stimulation without necessitating the destructive posterior root ablation.
Others have conducted more mechanistic investigations of conditioning stimuli delivered to the pudenal, dorsal penile or clitoral nerve (Opisso et al. 2013, Martens et al. 2011; Goldman et al. 2008; Opisso et al. 2008; Spinelli et al. 2005; Previnaire et al. 1996; Kirkham et al. 2001; Wheeler et al. 1994) or magnetic stimulation applied over the sacral nerves (Bycroft et al. 2004) and achieved demonstrations of detrusor inhibition or increased bladder capacity under lower pressure. A small (n=11; Opisso et al. 2013) study of three days of dorsal genital nerve stimulation demonstrated the feasibility of at home, self-administered electrical stimulation to increase bladder capacities and void volumes. Previous work by this group (Opisso et al. 2008) showed that training towards self-administration versus automated stimulation was effective in select patients to achieve suppression of undesired detrusor contractions and ultimately increased bladder capacity. Similar results were achieved with conditional stimulation, using implanted or surface electrodes on the dorsal genital nerve to suppress involuntary detrusor contractions (Martens et al. 2011; Horvath et al. 2009; Dalmose et al. 2003). However, further developmental work on larger groups of patients in more rigorous study designs would be required before these or modified approaches could be incorporated clinically as an approach that permits bladder stimulation in the absence of deafferentation. For example, semi-conditional stimulation, which conserves battery life, was also shown to be significantly effective for detrusor overactivity inhibition to increase bladder volume in patients with SCI (Lee et al. 2011). External stimulators, electrodes, cables and tolerance to electrical stimulation in the presence of preserved sensation are considered by patients to be hindrances to acceptability of this intervention (Opisso et al. 2013).
Lee et al. (2005) reported on a group of seven subjects with SCI where transcutaneous versus percutaneous electrical stimulation of the DPN was compared for effectiveness of bladder storage functionality. Although the percutaneous method was superior to the limitations of surface electrodes (e.g., daily donning/doffing, consistent placement and impedance) used for the transcutaneous method, the materials available for percutaneous electrodes are not yet sufficiently durable for long term use. Furthermore, percutaneous stimulation electrodes require precise positioning and potentially introduce a source of infection risk.
In a subsequent report, Lee et al. (2012) presented data from a small (n=6) group of males with SCI and complicated bladder function, using surface electrical stimulation to modulate bladder function. The stimulation paradigm consisted of initial current delivery to the dorsal penile nerve voluntarily triggered after perception of the first bladder contraction and followed by cyclic on-off stimulation parameters pre-determined during a 2-3 day admission to rehabilitation. Vesicoureteral reflux resolved in four cases and bladder wall deformity improved in 5 of the 6 cases, after treatment. Despite the improvement to bladder capacity and compliance, only short-term clinical efficacy was reported. To be a viable longer-term viable solution, not only would long-term follow-up data be required but also patient reported correlates would be required given the potential technical difficulties of this semiconditional stimulation treatment. Dexterity requirements for those with tetraplegia and interference from urine and sweat are among the possible feasibility and acceptability deterrents for this new treatment option.
The importance of current strength of pudendal nerve stimulation for short-term detrusor hyperreflexia inhibition has been explored in chronic suprasacral SCI (Previnaire et al. 1996; Wheeler et al. 1992; Vodusek et al. 1986). During cystometries, current strength at 2.0-3.5 times the bulbocavernosus reflex threshold was required to achieve functional inhibition. However, the subsequent study by Previnaire et al. (1998) determined that daily (i.e., 20 min/day, 5x/wk for 4 wk) stimulation at strengths equal to or above 99 mA applied to the pudendal nerve did not achieve efficacious inhibition of detrusor hyperreflexia.
Yoo et al. 2009 investigated the utility of an intraurethral stimulating catheter to selectively activate the proximal or distal segments of the urethra in 7 individuals with overactive bladder activity secondary to SCI. Although the study confirmed the existence of the pudendal nerve portion of the micturition reflex, further study of the stimulation parameters is required to be able to overcome detrusor dyssynergia and achieve bladder emptying.
Further developmental work would be required before these or modified approaches could be incorporated clinically to improve bladder function when afferent connectivity is intact. Sanders et al. (2011) reported that patients would choose minimally invasive electrode methods to improve bladder function as compared to more invasive methods such as use of the Brindley device (with or without rhizotomy).
Recently, Possover et al. (2009) reported a new surgical technique applied to persons with SCI involving laparoscopic transperitoneal implantation of neural electrodes to pelveoabdominal nerves, which they have termed the ‘‘LION procedure’’ (i.e., Laparoscopic Implantation of Neuroprosthesis). With this method, which is far less invasive than the traditional dorsal approach for stimulator implantation, the risk associated with immediate or long-term complications (e.g., meningitis, encephalitis, infections) is significantly reduced. In addition, the destructive procedures of rhizotomy and laminectomy are not necessary. Possover (2009) conducted this procedure on a series of eight persons previously having an explanted Brindley-Finetech stimulator, six of whom had viable sacral nerves. This resulted in adequate detrusor contractions enabling complete bladder emptying still present at follow-up (3-27 months). Patients undergoing this procedure returned home after only a 3-5 day hospital stay and there were no reported complications.
Another approach has been to apply stimulation to the bladder itself, most appropriately done during initial rehabilitation (Madersbacher et al. 1982; Radziszewski et al. 2009). Radziszweski et al. (2009) applied daily 15 minute bouts of transcutaneous electrical stimulation directly to the bladder for 30 days in patients seen by the Rehabilitation Department of a Military Hospital (time since injury not reported). These authors demonstrated significant increases in bladder capacity and peak flow velocity and a significant decrease in residual urine volume immediately following stimulation and persisting at two months follow-up compared to baseline. Continued efficacy was reported by the same group in 2013 (Radziszewski et al. 2013).
A similar approach was reported by Madersbacher et al. (1982) in which stimulation, in the form of impulse packages applied to a saline filled bladder, was administered over a variable treatment period after which the treatment effect persisted up to one year when most subjects reported a definite waning of the benefits. Unlike other studies involving sacral neuromodulation, this was conducted on those more recently injured with 17 of 29 becoming continent and 10 others becoming socially dry without need for pads and urinals. This study involved a case series design but would have been much more powerful with the inclusion of a control group, given the potential for natural bladder recovery in individuals with more recent injuries. Further research would also be needed to examine safety information related to bladder pressure during voiding, and follow-up of any potential renal changes before considering this intervention.
Sievert et al. (2010) also capitalized on the concept of neural plasticity through early (upon confirmation of bladder acontractility) sacral neuromodulation and reported no instances of detrusor overactivity and urinary incontinence with normal bladder capacity, reduced UTI rates and improved bowel and erectile functionality without nerve damage. Although follow-up was reported for greater than 2 years, further investigations are needed to augment the small sample size (n=10) and involve fMRI to confirm plastic changes within the brain of those patients undergoing sacral neuromodulation versus those pharmacologically treated.
Other investigators have examined the effects on the urinary system associated with stimulation directed towards other targets For example, Katz et al. (1991) tested the effect of epidural dorsal spinal cord stimulation, intended primarily for spasticity relief, at T1 (for those with tetraplegia) or T11-T12 (for those with paraplegia). Wheeler et al. (1986) investigated the effect of 4 to 8 weeks of quadriceps muscle reconditioning by surface electrical stimulation (FES) bilaterally, intended primarily for strength and spasticity. In each case, these techniques had marginal effects on bladder function. However, in the latter experiment it was noted that some subjects did achieve beneficial changes in bladder function and that these tended to be most noticeable in the same subjects that showed positive improvements in strength and spasticity.
There is level 4 evidence (from six pre-post studies, one case series, and one observational study) that ongoing use of sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) is an effective method of bladder emptying resulting in reduced incontinence for the majority of those implanted. This is associated with increased bladder capacity and reduced post-void residual volume.
There is level 4 evidence (from four pre-post studies and one case series study) that sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) may be associated with reducing UTIs and autonomic dysreflexia.
There is level 4 evidence (from one pre-post study and one case series study; Madersbacher et al. 1982; Radziszweski et al. 2009) that direct bladder stimulation may result in reduced incontinence, increased bladder capacity and reduced residual volumes (with two year efficacy data from one study group) but requires further study as to its potential for larger scale clinical use.
There is level 4 evidence (from various single studies) that other forms of neuroanatomically-related stimulation (e.g., electrical conditioning stimulation to posterior sacral, pudenal, dorsal penile or clitoral nerve or surface magnetic sacral stimulation) may result in increased bladder capacity but require further study as to their potential clinical use. These non- or minimally invasive techniques are preferred by patients over more invasive methods such as use of the Brindley device, with or without rhizotomy.
There is level 2 evidence (from a one prospective controlled trial; Sievert et al. 2010) that repforts early sacral neuromodulation may improve management of lower urinary tract dysfunction. Further investigation is required to confirm the results and substantiate the hypothesis of resultant plastic changes of the brain.
There is level 4 evidence (from one case series study; Katz et al. 1991) that epidural dorsal spinal cord stimulation at T1 or T11 originally intended for reducing muscle spasticity may have little effect on bladder function.
There is level 4 evidence (from one pre-post study; Wheeler et al. 1986) that a program of functional electrical stimulation exercise involving the quadriceps muscle originally intended for enhancing muscle function and reducing muscle spasticity has only marginal (if any) effects on bladder function.
Sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) enhances bladder function and is an effective bladder management technique though the program (surgery and followup) requires significant expertise.
Direct bladder stimulation may be effective in reducing incontinence and increasing bladder capacity but requires further study.
Posterior sacral, pudenal,dorsal penile or clitoral nerve stimulation may be effective to increase bladder capacity but requires further study.
Early sacral neural modulation may improve management of lower urinary tract dysfunction but requires further study.