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Electrical Stimulation for Bladder Emptying (and Enhancing Volumes)

Although electrostimulation to enhance bladder volume and induce voiding has been studied since the 1950s it was not until the development of the Brindley anterior sacral nerve root stimulator, and subsequent implantation of the first device in a human in 1978 that widespread clinical applications have been available (Egon et al. 1998; Brindley et al. 1982). Others have noted the important role of Tanagho and Schmidt (1982) in developing this approach – also termed sacral neuromodulation – by conducting a series of experiments to elucidate the neuroanatomical basis of electrical stimulation in enhancing bladder function (Hassouna et al. 2003). Although there are several configurations, Creasey et al. (2001) described the system employed in most investigations (i.e., the Finetech-Brindley system) as consisting of an implanted internal stimulator-receiver which is controlled and powered via telemetered radio transmission by an external controller-transmitter. Cables and electrodes are also implanted which are held in contact with sacral nerves (i.e., often S2-S4). This system allows programmable stimulation patterns and permits control of both bowel and bladder function. Often dorsal sacral rhizotomy is performed at the same time as stimulator implantation (Vastenholt et al. 2003; Creasey et al. 2001; Egon et al. 1998; Martens et al. 2011).

Various investigators have examined other forms of stimulation including direct bladder stimulation (Madersbacher et al. 1982; Radziszewski et al. 2009, 2013) or stimulators intended for other purposes such as enhancing muscle functions for improving movement, spasticity or muscle strength (Katz et al. 1991; Wheeler et al. 1986). In addition, multi-functional stimulators may be configured to provide similar stimulation patterns to similar targets as the bladder-specific stimulators. A systematic review of dorsal genital nerve stimulation in a variety of patients with detrusor overactivity (Farag et al. 2012) confirms its utility in improving bladder capacity and incontinence. As noted previously (Section 3.2.1 Electrical Stimulation to Enhance Bladder Volumes), the present section describes studies that assess outcomes associated with both bladder emptying and bladder storage as appropriately configured stimulation may result in improvements in both of these functions.

Table 18 Stimulation Methods to Trigger Bladder Emptying and Enhance Bladder Volume

Author Year

Country
Research Design
Score
Total Sample Size

MethodsOutcome
Systematic Reviews
Ren et al. 2016

United Kingdom

Review of published articles from Jan1975-Jan2014

AMSTAR=6

N=20

Method: Conduct a literature review on electrical nerve stimulation to promote micturition.

Databases: PubMed

Level of evidence: Unknown

Questions/measures/hypothesis: No specific hypotheses were tested by the authors

1. Four methods of electrical nerve stimulation were reviewed, sacral anterior root stimulation and sacral deafferentation, modification of the Finetech-Brindley stimulator, pudendal nerve stimulation (PN), and sacral neuromodulation (SNM).

2. The Finetech-Brindley stimulator is discussed, as well as subsequent iterations of the device. From 1976-1992, 500 individuals were implanted with the device and after a mean follow-up of 4 years, 411 individuals still used their stimulators for micturition.

3. Further iterations of the device include the SARS/SDAF version which of the 440 SCI individuals who received the device, 95% still used it for micturition and 83% maintained continence at follow-up.

4. PN involves the contact of an electrode catheter with the PN trunk. This technique has not been deemed very successful as it could only produce low bladder contractions, which did not result in effective voiding.

5. SNM has had significant positive effects on individuals, such that 69% of individuals significantly improved and 5 no longer needed CISC, there were no major complications and 66% of individuals were still responsive after 55 mo follow-up.

Interventional Studies
Fergany et al. 2017

Egypt

RCT

PEDro=6

N=80

Population: Pulsed electromagnetic field therapy (PEMFT): Mean age=39.45±9.30yr; Gender: males=24, females=16; Etiology: SCI=40; Inclusion criteria: presence of neurogenic overactive bladder.

Transcutaneous electrical nerve stimulation (TENS): Mean age=40.85±8.37yr; Gender: males=26, females=14; Etiology: SCI=40; Inclusion criteria: presence of neurogenic overactive bladder.

Intervention: Participants in the PEMFT group received sacral PEMFT consisting of 5 Hz with a 15% intensity output for 5s/min. Participants in the TENS group received sacral TENS consisting of 10 Hz with a generated pulse of 700 s. Both groups had 20 min/session, 3x/wk, for 20 sessions. Outcome measures were assessed at baseline and post-intervention.

Outcome Measures: urinary flow rate (Qmax); max. cystometric capacity (MCC); volume at first uninhibited detrusor activity (dV).

1. Both groups showed significant increases in MCC (p=0.001), dV (p=0.001), and Qmax (p=0.001).

2. Post-intervention values were significantly greater in PEMFT for MCC (p=0.001), dV (p=0.002), and Qmax (p=0.021).

Jo et al. 2016

Korea

RCT

PEDro=6

N=10

Population: Neurogenic detrusor overactivity; Mean age: 41.2 yr; Gender: males=7, females=3; ASIA classification: A/B.

Intervention: Individuals were randomized to receive percutaneous bipolar radiofrequency neurotomy on both the S2 and S3 nerves (n=5) or conventional medical treatment (n=5). Two-year follow-up of Kim et al. 2015.

Outcome Measures: Frequency of incontinence, volume of incontinence, International Consultation on Incontinence Questionnaire (ICIQ), urinary incontinence quality of life scale (I-QOL), maximum cystometric capacity, maximum detrusor pressure during filling, volume at maximal detrusor pressure during filling, reflex detrusor volume at first contraction.

1. With measurements at baseline, 6 mo, 12 mo, and 24 mo follow-up, daily mean volume of incontinence showed a significant group effect (p<0.05) but no time effect. ICIQ showed a significant time (p=0.000), group (p=0.049), and time by group interaction effect (p=0.000). Frequency of incontinence showed only a significant time effect (p=0.003) and a significant time by group interaction (p=0.001). I-QOL showed only a significant time effect (p=0.025) and a significant time by group interaction (p=0.001).

2. Reflex detrusor volume at first contraction (p=0.009), maximum detrusor pressure during filling (p=0.028), volume at maximal detrusor pressure during filling (p=0.009) and maximum cystometric capacity (p=0.028) all showed significant intergroup differences in terms of improvement from baseline to 24 mo follow-up.

Chen et al. 2015

China

RCT

PEDro=6

Ninitial=100; Nfinal=98

Population: Neurogenic detrusor overactivity; Mean age: 33.2 yr; Gender: males=91, females=6; Level of injury: cervical=28, thoracic=47, lumbar=23; Severity of injury: complete=75, incomplete=23; Mean time post-injury: 3.4 yr.

Intervention: Individuals were randomized to receive 1) percutaneous tibial nerve stimulation (PTNS group), consisting of surface electrodes placed at the ankle over the course of the tibia nerve for 30 min, 2 times per week, for 4 weeks or 2) solifenacin succinate (SS group), with 5 mg once a day for 4 weeks.

Outcome Measures: Clean intermittent catherization (CIC) frequency, fluid intake, volume per catherization, total leakage volume per day, Incontinence Quality of Life (I-QOL), adverse events.

1. No significant differences were observed post-treatment and between groups in terms of CIC frequency and fluid intake.

2. Compared to baseline, the volume per catherization significantly increased (p<0.05), the total leakage volume per day decreased (p<0.05), and the I-QOL significantly improved (p<0.05) for both groups at 2 wk and 4 wk follow-up. However, no significant differences were observed between 2 wk and 4 wk follow-up within groups, or between groups.

3. No adverse events were reported in PTNS group, compared to 5 participants in SS group reporting dry mouth (2 resulting in study discontinuation).

Kim et al. 2015

Korea

RCT

PEDro=6

N=10

Population: Neurogenic detrusor overactivity; Mean age: 41.2 yr; Gender: males=7, females=3; Level of injury: cervical=5, thoracic=5; ASIA classification: A=7, B=3.

Intervention:  Individuals were randomized to receive percutaneous bipolar continuous radiofrequency ablation of S2/S3 nerves (n=5) or conventional medical treatment (n=5).

Outcome Measures: Frequency of incontinence, volume of incontinence, International Consultation on Incontinence Questionnaire (ICIQ), urinary incontinence quality of life scale (I-QOL), maximum cystometric capacity (MCC), maximum detrusor pressure during filling (MDP), volume at maximal detrusor pressure during filling (volume at MDP), reflex detrusor volume at first contraction (RDV).

1. With measurements at baseline, 1 mo, and 3 mo follow-up, daily mean volume of incontinence showed a significant time effect (0.043) and group effect (0.012), but not a significant time by group interaction. ICIQ showed a significant time effect (p=0.005) and time by group interaction (p=0.020), but not a significant group effect. Frequency of incontinence showed a significant time effect (0.004) and time by group effect (p=0.003), but not a significant group effect. I-QOL showed a significant time effect (0.024) and time by group interaction (p=0.007), but not a significant group effect.

2. RDV (p=0.029) and volume at MDP (p=0.029) showed significant intergroup differences in terms of improvement from baseline to 3 mo follow-up, while MDP and MCC showed no significant differences.

Shendy et al. 2015

Egypt

RCT

PEDro=6

N=30

Population: Transcutaneous electrical nerve stimulation (TENS group): Mean age=28.1 yr; Pelvic floor biofeedback (PFBFB group): Mean age=28.3 yr.

Intervention: Individuals with precipitancy overactive bladder and erectile dysfunction were randomized to 1) TENS, which involved two surface electrodes placed directly over the skin of S2 for 30 min at 50 Hz (n=15) or 2) PFBFB, which involved contraction of the pelvic floor muscles in the fowler lying position while watching the electromyography biofeedback activities (n=15). Both groups performed pelvic floor exercises, 90 contractions per day after training session.

Outcome Measures: Bladder volume at first desire to void, maximum bladder capacity, maximum flow rate, detrusor pressure at maximum flow rate, right side amplitude per time (A/T), left side A/T, right side upper centile amplitude (UCA), left side UCA, International Index of Erectile Function Questionnaire (IIEF-5).

1. After treatment, bladder volume at first desire to void (p=0.001), maximum cystometric capacity (p=0.001), detrusor pressure at maximum flow rate (p=0.002), and maximum flow rate (p=0.001) significantly increased in TENS group but only the maximum flow rate (p=0.042) significantly increased in the PFBFB group. There were no significant differences between groups, except for the detrusor pressure at maximum flow rate being significantly higher in the TENS group both before (p=0.008) and after (p=0.001) treatment.

2. Post-treatment, the TENS group had significantly higher right side A/T (p=0.001), left side A/T (p=0.001), right side UCA (p=0.029), left side UCE (p=0.041), and IIEF-5 (p=0.013) compared to PFBFB group.

3. In terms of right side A/T, left side A/T, right side UCA, left side UCA, and IIEF-5, PFBFB group did not have any significant increases post-treatment while TENS had significant increases post-treatment (p=0.001).

Radziszewski et al. 2013

Poland

*Follow-up study to Radziszewski et al. 2009

Pre-post

N=28

Population: Age range 16-68 yr; Gender: males=22, females=6; Time post-injury: 2-26 mo.

Intervention: Transcutaneous electrical stimulation (ES) of the urinary bladder as a treatment for micturition disorders in individuals after SCI.

Outcome Measures: Bladder capacity, post-void residual urine, opening pressure, intravesical pressure, and maximum flow.

1. Transcutaneous ES of the urinary bladder produced a significant increase in bladder capacity (p=0.001).

2. Post-void residual urine in the urinary bladder decreased by a mean of 81.9 ml (p=0.007).

3. ES reduced bladder opening pressure in 16 individuals (57.1%) immediately after the treatment, by a mean of 4.5 cm H2O.

4. At follow-up (2 yr) intravesical pressure at maximum flow was lower than baseline in 21 individuals (79%), by a mean of 9.6 cm H2O (p>0.05).

Martens et al. 2011

Netherlands

Prospective Controlled Trial

N=101

Population: Gender: males=80, females=21; 73 SCI individuals with dorsal rhizotomy and Brindley stimulator (46 still used stimulator (Brindley group), 27 did not (Rhizotomy group); 28 control; Complete injury and detrusor overactivity.

Brindley group: Mean age: 48 yr, Mean time post-injury: 21 yr, Mean follow-up time: 13 yr. Rhizotomy group: Mean age: 47 yr, Mean time post-injury: 19yr, Mean follow-up time: 14 yr.

Intervention: Brindley stimulator or Rhizotomy.

Outcome Measures: Qualiveen Questionnaire, SF 36, Specific Impact of Urinary Problems score and clinical outcomes, quality of life (QoL).

1. The Brindley group had better QoL scores on every item in Qualiveen scale including limitations, constraints, fears, and bad feelings compared to control group (p=0.046).

2. The Brindley group also had a higher score in SF-36 compared to the rhizotomy and control group. The Brindley group reported a lower rate of urinary tract infection (UTI) and higher continence rate.

3. Fifty two percent of individuals in the brindley group reported complete continence compared to the control group (p=0.002) and the Rhizotomy Group (p=0.214).

Sievert et al. 2010

Germany

Prospective Controlled Trial

N=16

Population: Detrusor areflexia. Mean age: 31yr; Gender: males=16, females=0; Level of injury: T2/3-11=16; Severity of injury: complete=16, incomplete=0.

Intervention: Individuals with areflexic bladder were offered bilateral sacral neuromodulation treatment. Subjects refusing treatment (n=6) served as controls.

Outcome Measures: Bladder pressure, detrusor contractions, erectile function, urinary tract infection rate (UTI).

1. Improvement in bladder pressure and autonomic detrusor contractions was seen in the treatment group.

2. 2 individuals in the treatment group reported improved erectile function.

3. Individuals in the treatment group reported a mean of 0.5 UTIs/yr, while individuals in the control group reported 3.8.

Bycroft et al. 2004

UK

Prospective controlled trial

N=12

Population: SCI: Age range 19-46 yr; Gender: males=7, females=5; Level of injury: thoracic=7; Severity of injury: complete=7; Time post-injury=18-63 mo.

Intervention: A multi-pulse magnetic stimulator and coil was used to apply magnetic stimulation to sacral nerve roots at half capacity and near full capacity through single and intermittent bursts. In spinal cord injured individuals, stimulation was during neurogenic detrusor overactivity; while normal individuals received stimulation during voiding.

Outcome Measures: Bladder pressure, suppression of detrusor contractions.

1. No significant bladder pressure rise was seen in either single or intermittent bursts of magnetic stimulation of the sacral nerve roots.

2. Magnetic stimulation in spinal cord injured individuals resulted in suppressed detrusor overactivity and suppressed voiding in normal individuals.

Previnaire et al. 1996

France

Prospective Controlled Trial

N=20

Population: Mean age at injury: 32.4 yr; Gender: males=18, females=2; Time post-injury: 43.55mo; Level of injury: C4-T12; Severity of injury: tetraplegia complete=8, tetraplegia incomplete=4, paraplegia complete=4, paraplegia incomplete=4.

Intervention: Continuous electrical stimulation of dorsal penile or clitoris nerve via surface electrodes.

Outcome Measures: Bladder capacity and perineal contraction, adverse effects.

1. No significant difference in bladder capacity between T1, T2, T2.

2. No significant difference between the mean bladder capacities.

3. Significant increase in bladder capacity with electrical stimulation at twice the threshold compared with baseline and threshold cystometries.

4. The current of twice the threshold evoked a clinical perineal contraction in all individuals, threshold stimulation did not.

5. No adverse effects.

Goldman et al. 2008

USA

Prospective Controlled Trial

N=21

Population: Mean age: 52.7 yr (range 31-78 yr); Gender: males=0, females=21.

Intervention: Dorsal genital nerve stimulation.

Outcome Measures: Bladder diaries, 24hr pad tests, and adverse event queries.

1. 47% of subjects reported ≥50% reduction in incontinence episodes.

2. Pad weight was reduced by ≥50%

3. 7 subjects experienced 9 adverse events.

Bourbeau et al. 2018

USA

Pre-Post

N=5

Population: Mean age=66±8.4yr; Gender: N/S; Etiology: SCI=5; Time since injury=25.6±17.3yr.

Intervention: Participants received genital nerve stimulation (GNS). GNS was delivered through two circular electrodes applied to the dorsum of the penis. The cathode was placed at the base of the penis and the anode 2 cm distally. For females, one electrode was placed above the clitoris and the other on the lower labia majora or inner thigh. Participants underwent three one-month testing periods (baseline, stimulation, post-stimulation). A portable stimulator was used at home by the participants during the stimulation phase only (one-month duration). Outcome measures were assessed at baseline, and at the end of the stimulation and post-stimulation periods (each lasting one month).

Outcome Measures: Incontinence episodes (IE); bladder capacity

1. There was a significant decrease in IE from baseline to stimulation period (p<0.001).

2. There was a significant increase in IE at post-stimulation compared to the stimulation phase. Moreover, IE were still significantly lower than baseline (p<0.001).

3. There was no significant difference in bladder capacity across all time periods (p>0.05). However, bladder capacity did increased acutely during each urodynamics in response to GNS regardless of time period (p<0.001).

Brose et al. 2018

USA

Pre-Post

N=24

Population: Mean age=60±11yr; Etiology: SCI=24. Time since injury=13±4 yr; Inclusion criteria: presence of neurogenic detrusor over-activity (NDO).

Intervention: Genital nerve stimulation (GNS) was applied across two round surface electrodes. The cathode was placed on the proximal, dorsal end of the penis and the anode 2 cm distally (alternatively, the anode was a surface electrode placed on the mon pubis). For the female participants, the cathode was placed directly superior to the clitoris and the anode on the left lateral labia majora. Biphasic, charge-balanced, catholic-leading pulses were delivered at 20 Hz. Outcome measures were assessed at baseline and post-intervention.

Outcome Measures: Bladder capacity; bladder contractile inhibition.

1. Bladder capacity increased significantly (p=0.007).

2. 19 of 24 participants had delayed bladder contractions.

Gad et al. 2018

USA

Pre-Post

N=7

Population: Mean age=38.57±7.71yr; Gender: males=4, females=3; Etiology: SCI=7; Time since injury=5.66±7.23yr; Inclusion criteria=SCI at T11 or above; use intermittent catheterization to manage lower urinary tract (LUT).

Intervention: Participants received transcutaneous spinal cord stimulation (TSCS) delivered by 2.0 cm-diameter electrodes. Day1: Spinal stimulation was delivered at 0.5 Hz (individually at T11 and L1) with current starting at 10 mA and increasing at increments of 10-200 mA until tolerable or responses plateaued. Day 2: Transcutaneous electrical spinal stimulation for LUT functional augmentation (TESSLA) was delivered at 30 Hz and the bladder was filled until a detrusor contraction occurred. Stimulation was subsequently turned off and the bladder was emptied fully. The bladder was then filled to 75% and TESSLA was delivered at 1 Hz at T11 to initiate voiding. Outcome measures were assessed at baseline and during TESSLA.

Outcome Measures: Volume at first detrusor contraction (Vdet); voiding efficiency (VE); post-void residual (PVR); sensation of fullness; sensation of detrusor contraction; detrusor-sphincter dyssenergia; max. change in detrusor pressure during voiding; max. change in Pura during voiding.

1. TESSLA delivered at 1 HZ resulted in improved VE, flow rate, detrusor-sphincter coordination, and decreased PVR (p<0.05).

2. TESSLA delivered at 30 HZ at T11 resulted in significant improvements in bladder capacity and improved detrusor sphincter coordination during voiding (p<0.05).

3. When urodynamic studies were repeated after TESSLA was turned off, there was a reversal to baseline values.

Knight et al. 2017

UK

Pre-Post

N=6

Population: Gender: males=6; females=0; Etiology: SCI=8; Inclusion criteria: male subjects between the ages of 18-75 with a complete or incomplete supra-sacral SCI of at least 24 mo duration; presence of neurogenic detrusor overactivity (NDO).

Intervention: Conditional neuromodulation (CN) was applied using biphasic balanced pulses. Amplitude for each participant was determined based on sensory threshold or maximum tolerated. The bladder was filled at a physiological rate (15 mL/min) with CN applied simultaneously. A 60 s stimulation was triggered each time EMG threshold was met. Outcome measures were assessed at baseline and during CN.

Outcome Measures: Maximum cystometric capacity (MCC); maximum detrusor pressure (Pdet).

1. There was a significant increase in MCC (p<0.03) during NC.

2. There was a significant decrease Pdet (p<0.03) during NC.

Castano-Botero et al. 2016

Colombia

Pre-Post

N=104

Population: Neurogenic detrusor overactivity; Mean age: 38.0 yr; Gender: males=95, females=9; Level of injury: cervical=34, thoracic=68, lumbar=2; ASIA classification: A=96, B=8; Mean time post-injury: 72.8 mo; Injury etiology: traumatic spinal cord injury=103, other=1.

Intervention: Sacral anterior root stimulation (SARS), which involved laminectomy, posterior rhizotomy, implantation of electrodes, and tunneling.

Outcome Measures: Urinary infection, urinary incontinence, autonomic dysreflexia, cystometric bladder capacity, post-void residual (PVR) volume, adverse events.

1. The percentage of urinary infection (p<0.001), urinary incontinence (p<0.001), and autonomic dysreflexia (p<0.001) significantly decreased post-treatment.

2. Post-treatment, the mean bladder capacity was 362 mL, with 94% of participants having a bladder capacity greater than 400 mL and 91% of participants achieving effective voluntary voiding (PVR<50 ml).

3. In terms of adverse events, 6% required a suburethral mesh, 2% had an infection, 2% had electrode extrusion, 2% had receiver block extrusion, and 1% had device failure at 6 mo.

McCoin et al. 2015

United States

Pre-Post

N=10

 

Population: Bladder and sphincter spasticity; Gender: males=9, females=1; Level of injury: cervical=5, thoracic=5; ASIA classification: A=4, B=4, C=1, D=1.

Intervention: The bladder was filled with sterile saline at 20 ml/min until reflexive bladder contractions were observed. During reflex contractions, patterned electrical stimulation was randomly applied to the S2/S3 dermatome in 25 sec intervals.

Outcome Measures: Urethral sphincter pressure, vesical pressure, adverse events.

1. Of the six participants with detectable urethral reflex activity, none demonstrated urethral reflex suppression in response to any of the stimulation patterns. Stimulation did not have any significant effect on urethral pressure or bladder pressure.

2. No participants reported pain or adverse sensation during stimulation. One participant experienced two episodes of elevated blood pressure with a filled bladder, and three participants experienced one or more lower limb spasms.

Ojha et al. 2015

India

Pre-Post

N=15

Population: Detrusor overactivity; Posterior tibial nerve (PTN group): Mean age: 32.3 yr, Gender: males=9, females=1; Level of injury: C6-T3=1, T4-T10=6, T11-L3=3; Severity of injury: complete=6, incomplete=4; ASIA classification: A=5, B=1, C=3, D=1; Median time post-injury: 9.5 mo. Dorsal penile nerve (DPN group): Mean age: 42.8 yr; Gender: male; Level of injury: T4-T10=3, T11-L3=2; Severity of injury: complete; ASIA classification: A=4, B=1.

Intervention: Individuals with intact F-wave were recruited into the PTN study (n=10) and those with an absent F-wave were recruited into the DPN study (n=5). Individuals received electrical stimulation for 20 min per session each day for 14 consecutive days at the assigned site.

Outcome Measures: Reflex volume, cystometric capacity, maximum detrusor pressure, voiding diary improvement (no change or an increase in number of leaks and decrease in maximum volume of urine voided were considered to denote lack of improvement).

1. In the PTN study, the post-intervention mean reflex volume increased by 37.9 ml, the mean maximum pressure decreased by 8 cm H2O, and the mean cystometric capacity increased by 56 ml. There were no significant differences for any parameter comparing pre- and post-treatment.

2. In the DPN study, the post-intervention mean reflex volume increased by 46.8 ml, the mean maximum pressure decreased by 42.4 cm H2O, and the mean cystometric capacity increased by 59.6 ml. There were no significant differences for any parameter comparing pre- and post-treatment.

3. In the PTN study, 9 participants improved and 1 did not, with a statistically significant binomial distribution test (p=0.021).

4. In the DPN study, 5 participants improved and 0 did not, with a non-statistically significant binomial distribution test (p=0.062).

Lee et al. 2012

Korea

Pre-Post

N=6

Population: Age range 33-59 yr; Gender: males=6, females=0.

Intervention: Semi-conditional stimulation parameters were set during cystometry (CGN) and semi-conditional stimulation on dorsal penile nerve (DPN) by surface electrodes applied from 14 to 28 d, at home.

Outcome Measures: Bladder contraction, clinical bladder capacity, bladder compliance, initial bladder volume, maximum bladder volume.

1. The capacity of the bladder increased in all individuals after 2–4 wk of treatment.

2. Clinical bladder capacity measured by the voiding volume upon reflex voiding, and clean IC increased from 201.67±106.10ml to 383.33±51.64ml after treatment.

3. Bladder compliance improved from 3.30±1.89 ml per cm H2O before treatment to 11.26±9.18ml per cm H2O after treatment.

4. Vinitial increased from 45.17±23.84 to 165.5±156.5ml after treatment.

5. Vmaximum increased from 203.67±77.55 to 359.50±70.43ml after treatment.

Possover 2009

Switzerland

Pre-Post

N=8

Population: Mean age: 42±9 yr; Level of injury: Thoracic; Severity of injury: complete.

Intervention: SCI individuals with previous explantation of a dorsal implanted Brindley Finetech controller underwent the LION procedure, a laparoscopic transperitoneal technique of implantation of neural electrodes.

Outcome Measures: Urodynamic assessment (Detrusor contraction), complications collected during follow-up for 3-27 mo.

1. 6 of 8 individuals were able to have procedure (remaining 2 had damage to sacral nerves).

2. Immediate detrusor contraction of up to 60cm of H2O in women and 90cm in men was seen after bilateral stimulation of S3/S4.

3. At follow-up (up to 27 mo), complete bladder emptying still occurred.

4. Complete control of spasticity and autonomic dysreflexia was seen with bilateral implantation of the neuromodulation electrodes.

5. No complications were seen postoperatively.

Radziszweski et al. 2009

Poland

Pre-Post

N=22

Population: Mean age: 32 yr; Gender: males=18; females=4; Level of injury: C=3, L=19.

Intervention: SCI individuals were administered transcutaneous electrical stimulation of bladder for 15 min over 30 successive days.

Outcome Measures: Urodynamics (cystometric capacity, flow velocity, residual urine), adverse events. Urodynamic assessment conducted pre- and immediately following 30 d treatment period and 2 mo post-treatment.

1. A significant increase in cystometric capacity of urinary bladder (p=0.001) and peak flow velocity (p<0.001), while a significant decrease of residual urine (p=0.008) was seen immediately after electrical stimulation and at 2 mo follow-up compared to baseline. However, no significant change was seen between immediately post stimulation and after 2 mo.

2. No significant changes were seen in opening pressure and intravesical pressure at peak urine flow.

3. No adverse events were reported.

Kutzenberger 2007

Germany

Pre-Post

N=464

Population: SCI individuals with neurogenic detrusor overactivity. Mean age: 33, Gender: males=244, females=220; Level of injury: paraplegia=274, tetraplegia=190.

Intervention: SCI individuals underwent sacral deafferentation and implantation of a sacral anterior root stimulator for neurogenic detrusor overactivity.

Outcome Measures: Continence, urinary tract infections (UTIs).

1. Sacral deafferentation (SDAF) resulted in treatment of detrusor overactivity in 442 individuals.

2. 385 individuals achieved continence.

3. SDAF and sacral anterior root stimulation (SARS) resulted in decrease incidence of UTIs from 6.3/yr to 1.2/yr.

Lee et al. 2005

Korea

Pre-Post

N=7

Population: Mean age: 39.85 yr; Gender: male=7, female=0; Mean time post-injury: 67.28 mo; Level of injury: C6-T11; Severity of injury: ASIA A=2, ASIA B=2, ASIA C=3.

Intervention: Percutaneous or transcutaneous electrical stimulation for 1 minute.

Outcome Measures: Infused volume of saline, duration of suppression at first and last reflex, peak detrusor pressure.

1. No significant difference of infused volume of saline at first or last reflex contraction.

2. No significant difference for duration of suppression for first and last reflex contraction.

3. No significant difference in Pini, Pmax and Psup.

4. Peak detrusor pressure was effectively suppressed by both percutaneous and transcutaneous electrical stimulation.

5. No medical complications in either stimulation technique.

Hansen et al. 2005

Denmark

Pre-Post

N=16

Population: Gender: males=14, females=2; Level of SCI: C4/5-L4/5; Severity of injury: complete=8, incomplete=6; Time post-injury=3 mo–36 yr.

Intervention: Stimulation of the penile/clitoral nerve was performed on individuals with a custom made battery driven stimulator. Amplitude of stimulation was increased until the bulbocavernosus reflex was elicited and an event driven stimulation of amplitude of 2 times bulbocavernosus was used.

Outcome Measures: Bladder capacity, bladder pressure, prevalence of leakage, tolerance.

1. At least 1 inhibited detrusor contraction was seen in 13 out of 16 individuals who underwent penile/clitoral nerve stimulation.

2. Automatic event driven electrical stimulation resulted in 40% increase in bladder capacity and 69% decrease in storage pressure.

3. Only one individual had leakage.

4. Stimulation was tolerated by all but one individual.

Kutzenberger et al. 2005

Germany

Pre-Post

N=464

Population: Gender: males=244, females=220; Level of injury: paraplegic=464.

Intervention: Individuals underwent sacral deafferentation and implantation of anterior root stimulator.

Outcome Measures: Success rate, continence, voiding, urinary tract infection (UTI) prevalence. Mean follow-up time= 6.6 yr (minimum>6 mo).

1. 437 individuals had successful sacral deafferentation.

2. 385 achieved continence.

3. Voiding voluntarily through anterior sacral root stimulation was seen in 420 individuals.

4. There was a decrease in urinary tract infections from 6.3/yr preoperatively to 1.2/yr postoperatively.

Spinelli. et al. 2005

Italy

Pre-Post

N=15

Population: Neurogenic detrusor overactivity; Mean age: 38 yr; Gender: males=8, females=7.

Intervention: Individuals with neurogenic detrusor overactivity underwent chronic pudendal nerve stimulation. Measures were assessed at baseline and 6 mo post-treatment.

Outcome Measures: Urodynamic evaluation measuring cystometric capacity and maximum pressure.

1. Urodynamic evaluation for 7 individuals who completed 6 mo follow-up:

2. Maximum cystometric capacity, ↑ from 153.3±49.9 to 331.4±110.7mL (p<0.01).

3. Maximum pressure, decreased from 66.0±24.3 to 36.8±35.9 cm H2O (p=0.059).

Kirkham et al. 2002

UK

Pre-Post

N=5

Population: Age Range 32-46 yr; Level of injury: thoracic=5; Severity of injury: complete=5.

Intervention: Finetech-Brindley stimulator was implanted in individuals without rhizotomy of the posterior roots.

Outcome Measures: Bladder capacity, bladder pressures.

1. Postoperatively 2 individuals no longer presented with detrusor hyperreflexia.

2. Neuromodulation resulted in increased bladder capacity of all individuals.

3. 2 of 3 individuals had their bladder capacity increase more than double through continuous stimulation.

4. Intense stimulation in 3 individuals resulted in bladder pressures greater than 70cm H20.

Hohenfellner et al. 2001

Germany

Pre-Post

N=27

Population: Mean age: 44.9 yr (18-63 yr); Gender: males=8, females=19; Underlying neurological disorder: lesions of spinal cord=16; pelvic surgery=6; cerebral lesions=3; inflammatory disease of central nervous system (CNS)=2.

Intervention: Investigate the therapeutic value of sacral neuromodulation for rehabilitation of hypersensitive, hyperreflexic, or areflexic bladders.

Outcome Measures: Day and night time frequency; first desire to void (mL); bladder capacity (mL).

1. Test simulation was successful in 13 individuals.

2. In 2 of 3 individuals with failure to empty, the residual urine volume was reduced from 30 mL to 0 mL.

3. Therapeutic effect lasted 11 to 96 mo (mean 54 mo).

Creasey et al. 2001

USA

Pre-Post

N=23

Population: SCI: Mean age: 40 yr; Gender: males=16, females=7; Severity of injury: Complete; Level of injury: suprasacral (C4-T12); Median time post-injury=7 yr.

Intervention: Implantation of externally controlled neuroprosthesis for stimulating the sacral nerves and posterior sacral rhizotomy. Collected at baseline, 3 mo and 12 mo post-implantation.

Outcome Measures: Voided and residual volumes, catheter use, urinary tract infections (UTIs), anticholinergic use, autonomic dysreflexia, incontinence, satisfaction.

1. At 3 mo, 19/21 were successful in voiding more than 200mL of urine on demand, while 17/21 achieved residual volumes of less than 50mL. These results were maintained at 12 mo and were compared to 4/23 and 3/23 respectively prior to implantation (p<0.001).

2. Median voided volume  (p<0.001) and residual volume ↓ (p<0.001) as compared to baseline.

3. Continence was improved in 12 of 17 who completed 12 mo diaries

4. By 12 mo 18/23 people used the system as their primary bladder management method.

5. Decrease in median number of reported UTIs/person/yr from 3 to 2 at 12 mo, number of people using anticholinergics (17 to 2 at 12 mo) and number of people experiencing autonomic dysreflexia (8 to 2 at 12 mo).

6. Most people were satisfied with device.

7. Also helped with bowel management. 15 of 17 reduced time spend on bowel management; median time was halved (p<0.001).

Kirkham et al. 2001 England

Pre-Post

N=14

Population: SCI: Gender: males=14, females=0; Level of injury: C6 – L1; Time post-injury>1 yr.

Intervention: Different patterns of dorsal penile nerve stimulation (continuous or conditional which was a one minute burst triggered by a rise in detrusor pressure of 10cm H2O) assessed during urodynamic evaluation.

Outcome Measures: Urodynamic parameters (bladder capacity, bladder compliance). Collected prior and during/following stimulation.

1. Both continuous and conditional stimulation increased bladder capacity.

2. Continuous stimulation increased bladder compliance.

3. Of 6 subjects in which both stimulation methods were tested, 4 showed increased bladder capacity with the conditional versus continuous method but the difference was not significant.

4. The authors suggest the conditional neuromodulation method would be effective for use in an implanted device.

Egon et al. 1998

France

Pre-Post

N=96

Population: SCI: Mean age: 34.3 yr (males), 31.4 yr (females); Gender: males=68, females=28; Level of injury: paraplegia=55, tetraplegia=41; Time post-injury: 6.9 yr (males), 6.1 yr (females); Follow-up time=5.4 yr (males), 5.8 yr (females).

Intervention: ≥6 mo follow-up of those implanted with Finetech-Brindley sacral anterior root stimulator and in most cases posterior sacral rhizotomy.

Outcome Measures: Urodynamic assessment prior and at follow-up as noted above.

1. Bladder capacity increased from 242±120 to 567±51mL for males and from 118±80 to 560±43 ml for females.

2. 56 of 65 surviving males and 26 of 28 females were all continent. All but 1 female was incontinent prior. 5 individuals required an anticholinergic for continence.

3. 58 males and 25 females used the stimulator for bladder emptying with a residual volume of<50 ml.

4. Urinary tract infections (UTIs) ↓. 4 reported at least 1 UTI after, 35 prior.

5. Some reported ↑ spasticity which was transitory, pre-existing autonomic dysreflexia in 22 with bladder filling ceased.

6. 2 stimulators became infected, 5 stimulators failed, 3 had cable failures.

Previnaire et al. 1998

France

Pre-Post

N=6

Population: Mean age: 41.7±13.0 yr; Gender: males=5, females=1; Time post-injury: 9.3±5.5 mo; Severity of injury: tetraplegia incomplete ASIA B=3, tetraplegia incomplete ASIA C=1, paraplegia incomplete ASIA B=2.

Intervention: Pudendal nerve maximal electrical stimulation (MES) consisting of daily stimulation periods of 20 min, repeated five times a week, during 4 weeks, with continuous electrical stimulation of the penis or of the clitoris via bipolar surface electrodes (rectangular stimuli of 0.5 ms pulse duration, 5 Hz frequency).

Outcome Measures: Bladder capacity (mL) before and after MES.

1. There were no differences between cystometric bladder capacity volumes before or after MES.

 

Van Kerrebroeck et al. 1997

Netherlands

Pre-Post

N=52

Population: Mean age: 28.5 yr; Gender: males=41, females=11; Level of injury: cervical=11, thoracic=41; Mean time post-injury=6.4 yr.

Intervention: A Finetech-Brindley sacral anterior root stimulator was implanted and a complete posterior sacral root rhizotomy was performed on all individuals.

Outcome Measures: Bladder capacity, compliance, continence, urinary tract infections. Individuals were followed up 6 weeks after surgery, every 3 mo in the first yr, every 6 mo in the second yr, and once a yr afterwards.

1. Significant increase postoperatively was seen in bladder capacity at 6 wk and 6 mo (p=0.000) and compliance at 6 mo (p=0.000).

2. Complete continence at 6 mo was achieved in 38 individuals during the day and 45 during the night.

3. 38 individuals had no infection since the operation at 6 mo.

Van Kerrebroeck et al. 1996

Netherlands

Pre-Post

N=52

Population: Mean age: 32.9 yr; Gender: males=29, females=23; Etiology of injury: trauma=50; Level of injury: cervical=11, thoracic=41; Severity of injury: complete=52.

Intervention: Individuals underwent complete posterior sacral root rhizotomy and had a Finetech-Brindley sacral anterior root stimulator implanted.

Outcome Measures: Bladder capacity, continence, residual urine, urinary tract infections, complications. Follow up was done 6 wk after surgery and every 3 mo during the first yr.

1. Bladder capacity increased significantly in all individuals.

2. Complete continence was seen in 43 of the 52 individuals.

3. 41 individuals were able to use the stimulator alone to empty the bladder.

4. The prevalence of urinary tract infections decreased from 4.2 per yr to 1.4 per yr.

5. One individual had the implant removed due to infection.

 

 

Wheeler et al. 1994

USA

Pre-Post

N=9

Population: Mean age: 33.6 yr; Time post-injury: 2-26 yr.

Intervention: Pelvic floor stimulation via dorsal penile stimulation, consisting of stimulation frequencies of 2 and 5 pps and a max current of 50 mA.

Outcome Measures: Cystometric (CMG) bladder evaluation (filling bladder pressure and capacity, bladder contractile activity and sphincter electromyographic activity) and urologic status.

1. Two subjects successfully completed the study.

2. The most effective stimulating parameters was 5pps, 250msec pulse width and 40ma current.

3. In one of the individual who was satisfied with the protocol, bladder filling volumes increased from 110 to 150mL.

Wheeler et al. 1992

USA

Pre-Post

N=6

Population: Mean age: 36 yr; Gender: males=6, females=0; Time post-injury: 2-11 yr (mean 5.3 yr); Injury level: C6-T12

Intervention: Dorsal penile stimulation using a stimulation parameter of 5 pulses per second and pulse duration of 0.35 msec.

Outcome Measures: Cystometrographic filling volumes [baseline to post stimulation volumes (mL), percent of volume change from baseline to stimulation].

1. There was a significant increase in filling volume from before to during stimulation (127mL to 328 mL; mean 76% increase).

 

Robinson et al. 1988 England

Pre-Post

N=22

Population: SCI: Mean age: 30 yr; Gender: males=20, females=2; Level of injury: paraplegia=15, tetraplegia=7.

Intervention: Implantation of Brindley anterior sacral root stimulator.

Outcome Measures: Urodynamics, intravenous urography, continence. Collected prior and following implantation. Length of follow-up not stated.

1. No group results reported.

2. 16/22 using implant (11 continent, 5 incontinent).

3. Of 5 incontinent, 4 had hyperreflexia and these were unable to use stimulator with sufficient frequency.

4. 4 had hydronephrosis; 2 resolved after implant while 2 required sphincterotomy.

5. Total of 6 individuals required sphincterotomy.

6. 6 were able to sustain an erection, though not useful for intercourse due to associated stimulator induced muscle spasm.

7. Dyssynergia was noted as the main complication (n=6).

Wheeler et al. 1986

USA

Pre-Post

N=15

Population: SCI: Mean age: 47 yr; Gender: males=15; Level of injury: C5-T12; Time post-injury=4 mo–16 yr.

Intervention: 4 to 8 wk of quadriceps muscle reconditioning by functional electrical stimulation (FES) bilaterally intended for strength and spasticity.

Outcome Measures: Urodynamic assessment, strength (force transducer), spasticity (pendulum test). Collected prior and following stimulation program.

1. No group results reported.

2. In general, slightly more individuals had enhanced bladder function with treatment than those with no change or reduced bladder function.

3. 7 people had increased bladder capacity with pressure that decreased or stayed the same.

4. 6 people had decreased bladder capacity with pressure that increased or stayed the same; however 2 of these results were confounded by resolution of spinal shock.

5. Changes in bladder function were correlated with changes in strength and spasticity.

Vodusek et al. 1986

USA

Pre-Post

N=10

Population: Mean age: 24.9 yr; Gender: males=8, females=2; Time post-injury 5-96 mo (mean 30.2 mo); Level of injury: T=6, C=4.

Intervention: Electrical stimulation via the dorsal of the penis or dorsal clitoral nerve consisting of a repetitive stimulation (1Hz) with rectangular stimuli (0.2 or 0.5ms) and rate of 5 to 10Hz during bladder filling.

Outcome Measures: Micronutrient threshold (before, during and after stimulation; cc and percent).

1. Micronutrient threshold increased on stronger stimulation in seven individuals.

2. Post stimulation cystometry revealed a much lower micronutrient threshold than that obtained during stimulation.

Krebs et al. 2017

Switzerland

Post-Test

N=111

Population: Median age=50yr (28-77); Gender: males=59; females=52; Etiology: SCI=111; Time since injury=11.7yr; Inclusion criteria: individuals who received sacral intradural deafferentation of S2-S5 and implantation of an intradural anterior root stimulator after laminectomy from L4 to S2.

Intervention: Medical records of individuals who underwent sacral deafferentation (SDAF) and implantation of a sacral route stimulator were reviewed.  Outcome measures were assessed at 10 different time points post-intervention.

Outcome Measures: Max. detrusor pressure (Pdet); detrusor compliance (Dcom);

1. Pdet during stimulation showed a significant decrease over time (p<0.001).

2. Men had a significantly higher Pdet during stimulation compared to women (p<0.001).

3. There was no significant interaction effect between gender and time on Pdet during stimulation (p>0.05).

4. Pdet during the storage phase showed a significant decrease over time (p<0.001).

5. Dcom showed a significant increase over time (p<0.001).

6. Dcom was was not significantly different in males and females (p>0.05).

Yoo et al. 2009

USA

Post-Test

N=7

Population: Age range 22-66 yr; Gender: males=6, females=1; Level of injury: C5-T12.

Intervention: Randomized sequence of 6 trials that combined two stimulus amplitudes and three stimulation frequencies of intra-urethral electrical stimulation.

Outcome Measures: Distension evoked (DE) bladder contractions; bulbocavernosus reflex (BCR), proximal versus distal urethra activity, and detrusor pressure.

1. A DE bladder contraction was observed in 6/7 individuals.

2. A BCR was elicited in 5/7 participants

3. Electrical stimulation of the proximal urethra evoked sustained bladder activity in 3/7 participants

4. In 2 of the 7 participants, electrical stimulation of the distal urethra evoked excitatory bladder responses.

5. Pdet of proximal urethra was significantly greater than “non-responsive” bladder activity (p<0.05)
-Pdet of distal urethra was significantly greater than “non-responsive” bladder activity (p<0.05).

Wollner et al. 2016b

Switzerland

Case Series

N=50

Population: Neurogenic lower urinary tract dysfunction; Mean age: 46.3 yr; Gender: males=20, females=30; Level of injury: cervical=16, thoracic=7, lumbar=12, sacral=4; ASIA classification: A=3, B=2, C=11, D=19; Mean time post-injury: 9.5 yr; Injury etiology: spinal cord injury=35, myelomeningocele=2, multiple sclerosis=2, morbus Parkinson=1, other=10.

Intervention: Charts were reviewed for individuals who had received sacral neuromodulation (SNM) using bilateral tined leads implanted in the S3 or S4 sacral foramina. Successful test stimulation with >50% symptom improvement and individual satisfaction resulted in individuals receiving permanent implantation.

Outcome Measures: Test success, continence, frequency of bladder drainage per 24 hr, pad use in 24 hr, maximum bladder capacity, maximum detrusor pressure, compliance, individual satisfaction, post-void residual, complications.

1. Of the 50 participants undergoing the test phase, 26/39 neurogenic detrusor overactivity (NDO) participants and 9/11 urinary retention participants experienced test success and received permanent implantation.

2. There were 8 complications, with 2 infections and 6 technical defects.

3. In neurogenic overactive bladder participants, there were significant decreases in frequency of bladder drainage per 24 hr (p<0.05) and pad use in 24 hr (p<0.01) post-treatment, while there was a significant increase for compliance (p<0.046). There were no significant changes in terms of maximum bladder capacity or maximum detrusor pressure.

4. For the 26 successful NDO participants, 21 reported complete continence and 5 were incontinent.

5. For participants with chronic neurogenic urinary retention, all nine successes were able to void spontaneously and achieve continence. Post-treatment, there was a significant decrease in post void residual, while pad use, frequency of bladder evacuation, maximum bladder capacity, detrusor pressure, and compliance did not show significant changes.

6. Of the 32 participants with SNM use at last follow-up, 21 were very satisfied, 9 were satisfied, 1 was unchanged, and 1 was unsatisfied.

Chinier et al. 2016

France

Case Series

N=96

Population: Mean age: 36 yr; Gender: males=72, females=24; Level of injury: C7-C8=29, T1-T9=54, T10-L2=13; ASIA classification: A=89, B-D=7; Mean time post-injury: 6.5 yr.

Intervention: Records were reviewed for individuals who had received a Brindley neurostimulator implantation.

Outcome Measures: Stress incontinence, maximum urethral closure pressure (MUCP).

1. Compared to 93.8% of participants being incontinent prior to treatment, 10.4% experienced stress incontinence at one year post-treatment.

2. Compared to baseline, there was a significant decrease in the mean MUCP at 2-6 mo post-treatment.

3. Incompetent bladder neck (p<0.001) and previous urethral surgery (p=0.003) were significantly associated with stress incontinence. Age, gender, injury level, compliance, and MUCP were not significant predictors of stress incontinence.

Krebs et al. 2016

Switzerland

Case Series

N=130

Population: Charcot spinal arthropathy (CSA) group (n=11): Mean age: 36 yr; Gender: males=6, females=5; Level of injury: paraplegia=9, tetraplegia=2; Severity of injury: complete; Mean time post-injury: 13.7 yr.

Intervention: Medical records were reviewed for individuals who had underwent sacral deafferentation and sacral anterior root stimulation (SDAF/SARS), also known as the Brindley procedure.

Outcome Measures: Occurrence of CSA, time to diagnosis of CSA, stimulation failure or inadequate SARA-driven micturition (SARS dysfunction).

1. The proportion of CSA occurrence was significantly higher in participants with SARS dysfunction (7/41) compared to those without (4/89) (p=0.036).

2. The proportion of CSA occurrence was significantly higher in participants with SARS (11/130) compared to those without (17/3735) (p<0.00001).

3. CSA occurred a median of 8 yr after SDAF/SARS or 21 yr after spinal cord injury.

Krasmik et al. 2014

Switzerland

Case Series

N=137

 

Population: Mean age: 40.0 yr; Gender: males=81, females=56; Level of injury: cervical=53, thoracic=81, lumbar=3; Severity of injury: complete=132, incomplete=5; ASIA classification: A=132, B=4, C=1; Mean time post-injury: 11.6 yr.

Intervention: Charts were reviewed for individuals who had underwent sacral deafferentation and sacral anterior root stimulation (SDAF/SARS), also known as the Brindley procedure.

Outcome Measures: Detrusor pressure >40 cm H2O or detrusor compliance <20 ml/cm H2O or renal reflux (deafferentation failure), residual urine >100 mL or stimulator defect (stimulation failure), urinary incontinence, symptomatic urinary tract infection (UTI), urodynamic risk factors, antimuscarinic treatment, autonomic dysreflexia, complications.

1. With a mean follow-up of 14.8 yr, compared to pre-operatively, there were significantly fewer participants with high detrusor pressure (p<0.001), low detrusor compliance (p<0.001), renal reflux (p<0.001), one of more urodynamic risk factor (p=0.002), antimuscarinic treatment (p=0.03), urinary tract infections (p<0.001), and incontinence (p<0.001).

2. There were 17 participants with deafferentation failure, 14 participants with stimulation failure, and 6 participants with deafferentation and stimulation failure.

3. Mean bladder capacity significantly increased (p<0.001) and mean number of symptomatic UTI significantly decreased (p<0.001).

4. There were 84 complications leading to surgical revisions and 43 participants required additional urological interventions.

Lombardi et al. 2014

Italy

Case Series

N=85

Population: Neurogenic non-obstructive urinary retention (N-NOR); Mean age: 38.8 yr; Gender: males=52, females=33; Severity of injury: incomplete; ASIA classification: C=61, D=22; Etiology of injury: traumatic=62, vascular=3, myelitis=21.

Intervention: Data were reviewed for individuals who had undergone the percutaneous first stage of sacral neuromodulation (SNM).

Outcome Measures: Success of first stage SNM (responder), first sensation of bladder filling, volume of first sensation of bladder filling per ml, compliance, ability to void, maximum flow rate, detrusor pressure at maximum flow rate (PdetQmax), post void residual (PVR), or maximum urethral closure pressure.

1. At the end of the first stage of SNM, there were 36 responders and 49 non-responders.

2. For non-responders post-treatment, there were no significant differences compared to baseline in terms of first sensation of bladder filling, volume of first sensation of bladder filling per ml, compliance, ability to void, maximum flow rate, PdetQmax, PVR, or maximum urethral closure pressure.

3. For responders post-treatment, there were significant increases for first sensation of bladder filling (p<0.01), ability to void (p<0.01), maximum flow rate (p<0.01), PdetQmax (p<0.01), and PVR (p<0.01). Significant decreases compared to baseline were observed for PVR (p<0.01), and no significant differences were observed in terms of bladder capacity, compliance, or maximum urethral closure pressure.

4. The only significant predictive parameter for first stage SNM success was reported first sensation of bladder filling during cystometric filling at baseline (p=0.02). Complete N-NOR, duration of N-NOR, age over 40 yr, female gender, ASIA D, and traumatic etiology had no significant effect.

Gurung et al. 2012

England

*Follow-up from Khastgir et al. 2003

Case Series

N=19

Population: Mean age: 28.9 yr (12-52); Gender: males=12, females=7; Mean follow-up time: 14.7 yr (10.5-20.3); Mean time from injury to surgery: 4.5 yr (0.3-22 yr); Level of injury: Suprasacral=19.

Intervention: Augmentation ileocystoplasty (AIC).

Outcome Measures: Mean maximum cystometric capacity (MCC), Maximum detrusor pressure (MDP), and quality of life (QoL) questionnaire.

1. The increase in MCC was significant (p<0.001).

2. The reduction of MDP was significant (p<0.001).

3. QoL questionnaire showed 13/14 were satisfied with the outcome of the procedure, 1 individuals described being ‘unhappy’, 14 individuals reported no change in sexual function, 2 individuals reported being more constipated in recent years.

Lombardi & Del Popolo 2009

Italy

Case Series

N=24

Population: Mean age: 46 yr; Gender: males=14, females=10; retrospectively divided into 2 groups – urinary retention group with urodynamic evidence of underactive bladder and overactive bladder syndrome group.

Intervention: SCI individuals implanted with a sacral neuromodulation system (Medtronic).

Outcome Measures: Voiding symptoms collected with diary (number of voids, voided volume per void, number of urinary leakage episodes, pad use and nocturia for the overactive category, number of clean intermittent self-catheterization (CISC) for retention category) and adverse events collected at 1, 3, 6 mo and every 6 mo thereafter for a mean follow-up period of 60.7 mo (range=18-132 mo).

1. Individuals in the urinary retention group:

2. Increase in catheterized volume per catheterization, mean urinary frequency, mean voided volume, p<0.05.

3. Decrease in mean number of CISC, p<0.05

4. Individuals in the overactive bladder syndrome group:

5. Decrease in mean urinary frequency, mean number of urinary incontinence, mean pads used and nocturia, p<0.05

6. Increase in mean voided volume, p<0.05

7. 22 adverse events were reported – most prevalent were change in stimulation sensation (n=8), loss of efficacy (n=4) and pain/spasticity in leg (n=3).

Vastenholt et al. 2003 Netherlands

Case Series

N=37

Population: SCI: Mean age: 43 yr; Gender: males=32, females=5; Severity of injury: paraplegia=23, tetraplegia=14; Mean time post-injury=87 mo; Mean follow up time=86 mo.

Intervention: Long-term follow-up of those implanted with sacral anterior root stimulator.

Outcome Measures: Qualliveen questionnaire for quality of life (QoL) and impact of urinary problems, plus questions about effectiveness, side effects, advantages.

1. 32 of 37 still use the stimulator – complete continence for 21 during day and 26 at night. 27 reported an overall improvement in continence.

2. Urinary tract infections (UTIs) decreased with stimulator with majority saying they had>3/yr before and 0-2/yr after.

3. Significant increase in QoL as compared to a SCI reference group reported previously with various methods of management.

4. External technical failures=1/17 yr for cable breaks and 1/38 yr for transmitter defects.

5. Internal technical failures=1/66 user-yr.

6. Top advantages included reduction of UTI by 68%, increased social life by 54%, and increased continence by 54%.

Katz et al. 1991

USA

Case Series

N=33

Population: SCI: Mean age: 40 yr; Gender: males=31, females=2; Level of injury: paraplegia=12, tetraplegia=21; Mean time post-injury=83.6 mo.

Intervention: Implantation of epidural dorsal spinal cord stimulator at T1 (tetraplegia) or T11-T12 (paraplegia) intended primarily for spasticity relief.

Outcome Measures: Urodynamic parameters. Collected prior and 3 mo to 1 yr post-implantation.

1. For the most part, 17 of 23 evaluable individuals had no change in urodynamic values and mean urodynamic parameters showed no change (p>0.05).

2. 6 of these subjects had changes in lower urinary tract function but these changes were not systematic.

Madersbacher et al. 1982

Austria

Case Series

N=29

Population: SCI: Age range=8-60 yr; Gender: males=26, females=3; Level of injury: C5-S1; Severity of injury: incomplete; Time post-injury=3 mo.

Intervention: Impulse packages applied to a saline filled bladder. Minimum of ~50 stimulations for up to 90 min daily until maximal improvement is attained. Data collected prior to treatment and at un-specified follow-up time.

Outcome Measures: Urodynamic assessment, incontinence.

1. No group results reported.

2. 17 of 29 became continent, 10 others became socially dry without need for pads and urinals.

3. 26 gained perfect bladder sensation. 25 achieved satisfactory bladder contractions.

4. 28 had residual urine below 50 cc.

5. At one yr, individuals reported a reduced effect.

Discussion

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.

Conclusion

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.