Neurourology and Urodynamics 35:365–370 (2016)
Electrical Nerve Stimulation to Promote Micturition in Spinal Cord Injury Patients: A Review of Current Attempts 1
Jian Ren,1,2 Daniel J. Chew,3 Suzanne Biers,1 and Nikesh Thiruchelvam1* Department of Urology, Addenbrookes Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom 2 Department of Urology, China–Japan Friendship Hospital, Beijing, China 3 Department of Neurosciences, Addenbrookes Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom
Aims: In this review, we focus on the current attempts of electrical nerve stimulation for micturition in spinal cord injury (SCI) patients. Methods: A literature search was performed through PubMed using ‘‘spinal cord injury,’’ ‘‘electrical nerve stimulation AND bladder,’’ ‘‘sacral anterior root stimulation/stimulator’’ and ‘‘Brindley stimulator’’ from January 1975 to January 2014. Results: Twenty studies were selected for this review. Conclusion: Electrical nerve stimulation is a clinical option for promoting micturition in SCI patients. Well-designed, randomized and controlled studies are essential for further investigation. Neurourol. Urodynam. 35:365–370, 2016. # 2015 Wiley Periodicals, Inc. Key words: electrical nerve stimulation; neurogenic bladder; sacral anterior root stimulation; spinal cord injury INTRODUCTION
Normal bladder function depends on the integrity of central and peripheral nerve circuitry.1 This circuitry will be disrupted after spinal cord injury (SCI), leading to three main problems in bladder function: (i) detrusor-underactivity; (ii) detrusor-overactivity; and (iii) detrusor-sphincter dyssynergia (DSD).2 According to a UK consultation by questionnaire in 2010, only 21% of 142 SCI patients maintained normal voiding without the need for any other bladder management.3 In fact, most SCI patients will endure the devastating consequences of urinary retention, incontinence and infection. It will result in a poor quality of life (QoL) when the patients can not do clean intermittent selfcatheterization (CISC) but using indwelling transurethral or suprapubic catheter.3 It can also cause vesicoureteral reflux and damage to the upper urinary tract, even renal failure if left untreated for a long period. The Finetech-Brindley stimulator (Vocare1 system in USA), to our knowledge, is the only commercial functional electrical stimulation (FES) device applied clinically for micturition in SCI patients. It has been implanted in more than 2,000 individuals worldwide since 1970s. Although patients can use this equipment to empty their bladder, it seems that this procedure is not well accepted according to this relatively low number of implantations.4 It is important for clinicians and scientists to recognize the ways to improve the QoL, confidence and independence of patients suffering SCI.5 To gain an understanding of attempts to promote micturition in SCI patients, we have undertaken an expert review of electrical nerve stimulation in SCI patients. The aim of this review is to summarise current findings to date and stimulate debate and research in improving ways of enabling micturition among the SCI population. METHODS
A literature review was undertaken through a PubMed search by the primary author (JR) using the terms ‘‘spinal cord injury,’’ ‘‘electrical nerve stimulation AND bladder,’’ ‘‘sacral anterior root stimulation/stimulator’’ and ‘‘Brindley stimulator’’ from January 1975 to January 2014. The search was confined to additional filters, including having the abstract available, human species and in English. After reading the titles and abstracts, clinical #
2015 Wiley Periodicals, Inc.
papers directly relevant to electrical nerve stimulation for micturition in SCI patients were selected. Exclusion criteria were: (i) animal work; (ii) review paper; (iii) case report; and (iv) not relevant to bladder contraction, such as reports that only focused on the surgical techniques for implantation of the hardware or for detrusor overactivity. Manual inspection of the reference list of each selected article was performed to further identify studies that were not captured by the online search but that might be potentially relevant for the review. The second author (DC) and the senior author (NT) undertook a repeat search to ensure inclusion of all possible articles. Any question with regard to inclusion of a particular article, such as concern of bias or selective reporting, was resolved by discussion between the authors. As the number of clinical studies was low, bias was minimized by inclusion of all possible studies. This expert review was constructed by summarizing findings with presentation of results under thematic headings. The discussion was determined by expert consensus by the authors. RESULTS
The search resulted in 137 papers (see Fig. 1). After all abstracts were assessed and after relevant exclusion due to non-relevance, 25 full papers were accessed and reviewed. A further four papers were accessed following manual inspection. A further review of the identified 29 articles led to exclusion of nine papers. Those papers were excluded because: three of them focused on cost-effectiveness or QoL after implantation of the Finetech-Brindley system; one was focused only on the urodynamic result; the other five were relevant works undertaken by the same teams. There were two exceptions, Potential conflicts of interest: Nothing to disclose. Robert Pickard led the peer-review process as the Associate Editor responsible for the paper. Correspondence to: Nikesh Thiruchelvam, Department of Urology, Addenbrookes Hospital, Cambridge University Hospitals NHS Trust, Hills Road, Cambridge CB2 0QQ. E-mail: [email protected] Received 8 September 2014; Accepted 3 December 2014 Published online 8 February 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/nau.22730
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Fig. 1. Results of PubMed literature review (presented according to PRISMA additional records identified through reference sources (n ¼ 4).
one was a case report performed only through the pudendal nerve, and the other was the serial report performed by Brindley himself. Twenty full-text articles were assessed and summarized for this review. Some details were extracted from the papers and listed in Table I. Among these 20 studies, 14 were undertaken with the Brindley device,6–19 two used modified Brindley devices, which were the sacral anterior roots stimulation with anodal block20 and the Neurourology and Urodynamics DOI 10.1002/nau
sacral posterior and anterior roots stimulation (SPARS).21 Two used sacral neuromodulation,22,23 one with pudendal nerve,24 and one paper stimulated the whole or ventral sacral root.25 Sacral Anterior Root Stimulation and Sacral Deafferentation
The first application of a sacral anterior root stimulation (SARS) device was described and tested by GS Brindley in
Neurourology and Urodynamics DOI 10.1002/nau
30 500 47
12
10 96
35 23
5
Madersbacher, 1993 Brindley, 1994 Van Kerrebroeck, 1996
Rijkhoff,1998
Schurch, 1997 Egon, 1998
van der Aa, 1999 Creasey, 2001
Kirkham, 2002
13
29 137
Lombardi, 2009
Lombardi, 2009 Grasm€ ucke, 2013 (Epub)
55 months 14.8 4.8 years
Acute experiment 61 months
Sacral neuromodulation Sacral anterior roots
Sacral neuromodulation
Pudendal nerve trunk
Sacral posterior and anterior roots Sacral anterior roots
4 months 6.6 years
Sacral anterior roots Sacral anterior roots
0.25–12 years 1 year
Selective sacral anterior roots with anodal block Sacral anterior roots Sacral anterior roots
8 years 0.25–16 years 42.2 months Acute experiment 3.4 years 5.4–5.8 years
Sacral anterior roots Sacral anterior roots Sacral anterior roots
5–11 years 3–29 months
Stimulation site Sacral anterior roots Sacral anterior roots Sacral anterior roots The whole sacral root or sacral ventral roots Sacral anterior roots Sacral anterior roots
2–50 months 1–9 years – 6 years
Follow up
None 100%
None
None
94%
None
100% 100%
100% 100%
100%
100% 70% 100%
34% 100%
None 34% – 84%
Rhizotomy
66% 78%
69%
None
95%
20%
100% 78%
70% 89%
–
90% 86% 96%
82% 75%
100% 86% 73% 38%
Use for micturition
a
Other bladder management in those who use Electrical stimulation for micturition.
CSF, Cerebrospinal fluid; CIC, Clean intermittent catheterization; –, Date not reported or can not be concluded in the reference.
2
Yoo, 2007
440
50 12
Brindley, 1990 Sauerwein, 1990
Kutzenberger, 2005
11 50 22 19
Patients number
Brindley, 1982 Brindley, 1986 Robinson, 1988 Tanagho, 1989
Publications
TABLE I. Site of Stimulation and the Details From the Included References
4 patients with CIC, mean CISC number was 0.8 0.7 times daily – 22 condom catheters
–
3 with CIC 5 with CIC, 1 with indwelling catheter 3 with CIC, 1 with indwelling catheter –
– 10 with CIC
– 1 by CIC, 1 by indwelling catheter, 1 by abdominal straining 2 with Credes method – 4 patients with CIC 1 or 2 times daily –
– – – 1 with condom catheter
Combined bladder managementsa
– 62%
–
–
83%
–
84%
80% 89%
–
93% – 91%
77% 64%
59% 62% 68% 82%
Continence
None CSF leaks, 4 second deafferentation, implants removed CSF leaks, 3 receiver failures patients with stress incontinence
– 80 surgical revisions, 10 artificial sphincters, 4 second deafferentation
6 revisions for battery depletion
70 defects of the implant, 34 repair surgeries needed –
3 with persisting DSD
3 2 3 4
5 patients needed second rhizotomy 95 ops to remedy implants faults One implant infection needed remove, 3 second rhizotomy –
2 CSF leaks needed operation 14 CSF leaks 10 implant failures 6 DSD needed sphincterotomy 7 with pudendal neurotomy, 5 with levatorotomy 18 implant failures 1 CSF leak, 2 second rhizotomy needed
Main complications or other surgeries
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baboons in the 1970s, and then implanted in SCI patients in 1976. This device, which is now marketed as the FinetechBrindley stimulator, includes three intracorporeal components and an extracorporeal transmitter. The intracorporeal part has four slots, three cables and a receiver block. Each slot has three platinum foil electrodes. The external stimulator must be placed onto the position of the receiver block to evoke the device with low frequency (10–30Hz) waves. The electrodes can be placed intradurally or extradurally on the sacral roots S2-S4. For patients with intact EUS, electrical stimulation of the sacral roots especially in S3 and S4, generated contraction not only in the detrusor muscle but also in the EUS itself. If stimulation persisted, the sphincter permanently closed the bladder outlet and prevented micturition.6 In order to avoid this, an intermittent stimulation pattern was applied to induce poststimulus voiding. During the intermittent period (off stimulation), the striated muscle of EUS will relax immediately, but the detrusor smooth muscle undergoes a prolonged contraction emptying the bladder at a low pressure. Patients often need several courses of stimulation and subsequent flow to empty their bladder.26 Post-stimulus voiding by intermittent 30 Hz stimulation induced onto the sacral anterior roots allows the bladder to contract, while the sphincter undergoes periods of relaxation during the intermittent period to prevent dyssynergia. In order to eliminate the neurogenic detrusor overactivity, sacral deafferentation (SDAF) of the posterior roots of S2-S4/5 was applied.27 SDAF then became a routine procedure combined with SARS to improve bladder capacity, compliance and continence since the late 1980s. However, a severe consequence is that patients irreversibly lose their reflex erection and ejaculation in males and vaginal lubrication in females.28 It is important to note that this procedure demands surgical expertise for implantation, which may be another reason for the restricted use of this device. In 1986, Brindley reported implantation of the SARS in the first 50 patients.7 At the end of 1 to 9 years follow up, 43 patients still used the device regularly for micturition. In 91% (40/44) of patients, the residual volume of urine was less than 60 ml. Only two patients had deterioration of their upper urinary tract and four patients had three infections or more a year. Sacral deafferentation was not a routine step at that time, and only 10 patients underwent sacral posterior root rhizotomy. Another nine patients presented with increased bladder volume, and this may be partly attributed to the accidental injury of the posterior roots during implantation. From 1976 to 1992, Finetech-Brindley stimulators were implanted in 500 patients across 28 centers, mainly in the UK, Germany, France, Netherlands, New Zealand and Australia. After follow-up from 3 months to 16.1 years (mean 4 years), 411 patients still used their stimulators for micturition. 45 patients refrained from using the stimulator mainly because of weak detrusor responses. Most of them went back to CISC. Twentyone patients had died, due to circumstances unrelated to the device.12 Another large follow-up study was conducted by Kutzenbergen and colleagues, from 1986 to 2002. Of 440 SCI patients who received SARS/SDAF, 95% still used the device for micturition with a daily frequency of 4.7 times, and 83% maintained continence. Urinary tract infection (UTI) rates reduced from 6.3 to 1.2 times per year. Kidney function was € cke evaluated the results of stable.18 More recently, Grasmu SARS/SDAF by urodynamic tests. Among 137 patients, 107 (78%) were still using the device, the number of patients suffering from elevated detrusor pressure, low detrusor compliance, limited bladder capacity or incontinence were significantly reduced after implantation.19 Neurourology and Urodynamics DOI 10.1002/nau
Table I illustrates that most of the patients (70%–100%, when data available) would continue using their stimulator for micturition at the end of follow-up. Continence was also achieved in most of the reports were accompanied with SDAF, especially in the three larger studies.12,18,19 However, information on bladder management was not included in two of these three studies, and so we could not know exactly if the patients were completely free from clean intermittent catheterization (CIC) or used CIC as well as stimulation. Device faults and surgical revisions of the implants were the most common complications in long-term follow-ups. CSF leak became rare after the 1990s, possibly due to advancement of surgical technique. In the same period as Brindley’s 1970s studies, a team at the University of California, San Francisco evaluated the potential for evacuating the bladder by electrical stimulation of the bladder wall, pelvic nerve, spinal cord and sacral nerve29. Tanagho and colleagues reported 22 SCI patients with the stimulation of the whole sacral roots or the sacral ventral roots. However, the result was not satisfactory because only 38% of patients could use the stimulator for micturition. Half of patients needed pudendal neurotomy or levatorotomy even combined with rhizotomy, which were not common in the Brindley procedure.
Modification of the Finetech-Brindley Stimulator
As mentioned before, activation of the detrusor muscle was by accompanied stimulation induced DSD through the Brindley stimulator. Over the past 20 years, there have been a number of attempts to eliminate DSD or avoid rhizotomy for this procedure. In one acute experiment with 12 SCI patients during the implantation of a Finetech-Brindley stimulator combined with rhizotomy,20 the current through the larger nerve fiber was selectively blocked near the anodes due to the anodal current. This was achieved in eight patients. The sphincter was prevented from contraction with a 6.0 mA current, while the sphincter could also be switched on and off by a short duration current, which indicated that relaxation of the sphincter was not caused by fatigue nor damage to the nerve roots. However, anodal blocking could not be obtained in four patients. The author speculated that this could be due to excessive manipulation of the nerve roots during identification and electrode placing. Kirkham used the Finetech-Brindley device to set up SPARS in order to eliminate rhizotomy in an acute model.21 SPARS was implanted to the mixed sacral roots in five patients without rhizotomy. In three patients with postoperative bladder hyperreflexia, SPARS successfully inhibited hyperreflexia. Bladder contraction with a detrusor pressure more than 70 cm H2O could also be achieved by intense stimulation. However, DSD during the stimulation gap prevented the bladder from emptying. Only less than 50% amount of the urine was evacuated from the bladder.
Pudendal Nerve Stimulation
Pudendal nerve (PN) stimulation was conducted by a percutaneous catheter electrode in contact with the PN trunk. Two cases were tested acutely under this setting.24 In case 1, stimulation evoked a transient but relatively high (30 cm H2O) pressure. Urine leak could be achieved around the urethral catheter by repeated stimulation. In case 2, stimulation could only produce a low (9 cmH2O) bladder contraction, which did not result in effective voiding.
Electrical Nerve Stimulation to Promote Micturition in SCI Bladder Sacral Neuromodulation (SNM)
Lombardi reported the experience of SNM in 13 incomplete SCI patients with neurogenic non-obstructive urinary retention (NNOR).22 The SNM was permanently implanted 5.4 years (1–12 years) after the neurological diagnosis. Nine patients emptied their bladder completely by CIC before implantation, and the other four by Valsalva maneouver with increased residuals. Mean follow-up was 61 months (18–132 months). Nine (69%) patients were significantly improved by SNM, five of them no longer needed CISC, another four used mean CISC 0.8 0.7 times daily. Four patients were not improved after implantation due to detrusor underactivity. There were no major complications except for six revisions for battery depletion. However, a more recent study showed only 29 (38%) out of 77 incomplete SCI patients with N-NOR had a response to first stage SNM.23 Permanent implantation was performed in these patients. Nineteen (66%) patients were still responsive after 55 (6–107) months follow-up. Ten patients returned to baseline symptoms. The result was inconclusive because no effectiveness of the micturition by SNM and other bladder management were mentioned at the end point of the study. DISCUSSION
Regaining bladder function is the first shared priority of quadriplegics and paraplegics, even above the restoration of locomotion.30 Unfortunately, there is no simple solution to re-establishing and optimizing micturition for SCI patients. There is a lack of safe and effective drugs to treat bladder underactivity.31 Catheterization is a burden on the patient and has a social stigma affecting QoL,3 which is accompanied with a high prevalence of retrograde infection, urethral pain, haematuria and urethral stricture. Although it is the only commercial FES for bladder contraction until now, the Finetech-Brindley stimulator has not been well accepted across the world, when compared to the large numbers of patients with SCI who are catheter-dependent.4 The reason may be the unfamiliarity with this procedure by the patients and their doctors; fear of major spinal surgery, the prerequisition for and permanence of posterior root rhizotomy, and doubts about the effects of surgery. The cost of the Brindley device (42,803 euro in the first 12 months after implantation32) is a huge burden on healthcare providers and insurers, and prohibitive to patients in the poorer regions of the world. With respect to long term effectiveness and ease of use across a patient’s life time, complete and voluntary micturition by the Brindley procedure is much improved compared to conventional neurogenic bladder treatment.32 After implantation, the advantages of the Brindley procedure were reported as: reduction of infection rate (68%), improved social life (54%) and continence (54%), which were coincident with patients’ expectations, and accompanied with improved QoL.33 Despite advantages, defective stimulators or implants, inconvenience of leg spasms during stimulation, removal of infected implants and preference of other bladder emptying methods were the main reasons for no longer using the device.34 Refinement of the Finetech-Brindley system may advance re-uptake in the medical community. Subsequent DSD is still a big problem, and the results from this clinical review suggest its treatment is variable and inconclusive. SNM has some effect on bladder contraction without the need for rhizotomy. However, only preliminary data exists on this. Stimulation of the PN in animal models through different frequencies can achieve bladder contraction, EUS relaxation and stability of the detrusor muscle concurrently.35 This is a promising work, but the result of the only human test available was disappointing.24 Neurourology and Urodynamics DOI 10.1002/nau
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This review highlighted potential future avenues for research: (i) selective activation of the detrusor muscle, although excessively tested in animal model (data not shown) is too immature for clinical use; (ii) modification of the Finetech-Brindley stimulator to minimize the difficulty of implantation and complications; (iii) further study on other stimulation sites, for example, pudendal nerve stimulation; (iv) the mechanism of SNM on SCI-induced bladder dysfunction; and (v) combining available techniques with new strategies. This latter point may enable closed loop refinement in bladder electrical neuromodulation through recording bladder activity,36 whereby a stimulator or block will be reactive to the state of bladder fullness. CONCLUSION
Electrical nerve stimulation, mainly conducted with the Finetech-Brindley stimulator, is a considerable option for bladder management in SCI patients. However, there are as yet no randomized or controlled clinical trials, making it difficult to draw conclusions on optimal efficacy for neurogenic bladder treatment. Further work, both pre-clinically and clinically, is needed to refine neuromodulation treatment options for SCI patients. REFERENCES 1. Craggs MD, Balasubramaniam AV, Chung EAL, et al. Aberrant reflexes and function of the pelvic organs following spinal cord injury in man. Auton Neurosci Basic Clin 2006; 126–127:355–70. 2. Craggs MD. Pelvic somato-visceral reflexes after spinal cord injury: Measures of functional loss and partial preservation. Prog Brain Res 2006; 152:205–19. 3. Liu C-W, Attar KH, Gall A, et al. The relationship between bladder management and health-related quality of life in patients with spinal cord injury in the UK. Spinal Cord 2010; 48:319–24. 4. Wein AJ. Re: Quality of life in complete spinal cord injury patients with a brindley bladder stimulator compared to a matched control group. J Urol 2013; 189:613. 5. French JS, Anderson-Erisman KD, Sutter M. What do spinal cord injury consumers want? A review of spinal cord injury consumer priorities and neuroprosthesis from the 2008 neural interfaces conference. Neuromodulation J Int Neuromodulation Soc 2010; 13:229–31. 6. Brindley GS, Polkey CE, Rushton DN. Sacral anterior root stimulators for bladder control in paraplegia. Spinal Cord 1982; 20:365–81. 7. Brindley GS, Polkey CE, Rushton DN, et al. Sacral anterior root stimulators for bladder control in paraplegia: The first 50 cases. J Neurol Neurosurg Psychiatry 1986; 49:1104–14. 8. Robinson LQ, Grant A, Weston P, et al. Experience with the Brindley anterior sacral root stimulator. Br J Urol 1988; 62:553–7. 9. Brindley GS, Rushton DN. Long-term follow-up of patients with sacral anterior root stimulator implants. Paraplegia 1990; 28:469–75. 10. Sauerwein D, Ingunza W, Fischer J, et al. Extradural implantation of sacral anterior root stimulators. J Neurol Neurosurg Psychiatry 1990; 53:681–4. 11. Madersbacher H, Fischer J. Sacral anterior root stimulation: prerequisites and indications. Neurourol Urodyn 1993; 12:489–94. 12. Brindley GS. The first 500 patients with sacral anterior root stimulator implants: General description. Paraplegia 1994; 32:795–805. 13. Van Kerrebroeck PE, Koldewijn EL, Rosier PF, et al. Results of the treatment of neurogenic bladder dysfunction in spinal cord injury by sacral posterior root rhizotomy and anterior sacral root stimulation. J Urol 1996; 155: 1378–81. 14. Schurch B, Rodic B, Jeanmonod D. Posterior sacral rhizotomy and intradural anterior sacral root stimulation for treatment of the spastic bladder in spinal cord injured patients. J Urol 1997; 157:610–4. 15. Egon G, Barat M, Colombel P, et al. Implantation of anterior sacral root stimulators combined with posterior sacral rhizotomy in spinal injury patients. World J Urol 1998; 16:342–9. 16. Van der Aa HE, Alleman E, Nene Snoek AG. Sacral anterior root stimulation for bladder control: clinical results. Arch Physiol Biochem 1999; 107:248–56. 17. Creasey GH, Grill JH, Korsten M, et al. An implantable neuroprosthesis for restoring bladder and bowel control to patients with spinal cord injuries: A multicenter trial. Arch Phys Med Rehabil 2001; 82:1512–9. 18. Kutzenberger J, Domurath B, Sauerwein D. Spastic bladder and spinal cord injury: Seventeen years of experience with sacral deafferentation and implantation of an anterior root stimulator. Artif Organs 2005; 29:239–41.
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19. Grasm€ ucke D, Krebs J, van Ophoven A, et al. Urodynamic results, clinical efficacy, and complication rates of sacral intradural deafferentation and sacral anterior root stimulation in patients with neurogenic lower urinary tract dysfunction resulting from complete spinal cord injury. Neurourol Urodyn 2013; doi:10.1002/nau.22486 20. Rijkhoff NJ, Wijkstra H, van Kerrebroeck PE, et al. Selective detrusor activation by sacral ventral nerve-root stimulation: results of intraoperative testing in humans during implantation of a Finetech-Brindley system.. World J Urol 1998; 16:337–41. 21. Kirkham APS, Knight SL, Craggs MD, et al. Neuromodulation through sacral nerve roots 2 to 4 with a Finetech-Brindley sacral posterior and anterior root stimulator. Spinal Cord 2002; 40:272–81. 22. Lombardi G, Del Popolo G. Clinical outcome of sacral neuromodulation in incomplete spinal cord injured patients suffering from neurogenic lower urinary tract symptoms. Spinal Cord 2009; 47:486–91. 23. Lombardi G, Musco S, Celso M, et al. Intravesical electrostimulation versus sacral neuromodulation for incomplete spinal cord patients suffering from neurogenic non-obstructive urinary retention. Spinal Cord 2013; 51:571–8. 24. Yoo PB, Klein SM, Grafstein NH, et al. Pudendal nerve stimulation evokes reflex bladder contractions in persons with chronic spinal cord injury. Neurourol Urodyn 2007; 26:1020–3. 25. Tanagho EA, Schmidt RA, Orvis BR. Neural stimulation for control of voiding dysfunction: a preliminary report in 22 patients with serious neuropathic voiding disorders. JURO 1989; 142:340–5. 26. Brindley GS. An implant to empty the bladder or close the urethra. J Neurol Neurosurg Psychiatry 1977; 40:358–69.
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27. Sauerwein D. Funktionelle Elektrostimulation der Harnblase: Erste Erfahrungen mit sakraler Deafferentation und Vorderwurzelstimulation nach Brindley in Deutschland. Verh Dtsch Ges Urol 1988; 39:595–7. 28. Ragnarsson KT. Functional electrical stimulation after spinal cord injury: Current use, therapeutic effects and future directions. Spinal Cord 2008; 46:255–74. 29. Schmidt RA. The winding path to sacral foramen neural modulation: A historic chronology. Int Urogynecology J 2010; 21 Suppl:S431–8. 30. Anderson KD. Targeting recovery: Priorities of the spinal cord-injured population. J Neurotrauma 2004; 21:1371–83. 31. Andersson K-E. Bladder underactivity. Eur Urol 2014; 65:399–401. 32. Benard A, Verpillot E, Grandoulier AS, et al. Comparative cost-effectiveness analysis of sacral anterior root stimulation for rehabilitation of bladder dysfunction in spinal cord injured patients. Neurosurgery 2013; 73:600–8. Discussion 608. 33. Vastenholt JM, Snoek GJ, Buschman HP, et al. A 7-year follow-up of sacral anterior root stimulation for bladder control in patients with a spinal cord injury: Quality of life and users experiences. Spinal Cord 2003; 41:397–402. 34. Martens FMJ, den Hollander PP, Snoek GJ, et al. Quality of life in complete spinal cord injury patients with a Brindley bladder stimulator compared to a matched control group. Neurourol. Urodyn. 2011; 30:551–5. 35. Yang G, Wang J, Shen B, et al. Pudendal nerve stimulation and block by a wireless-controlled implantable stimulator in cats. Neuromodulation 2014;17:490–6. 36. Chew DJ, Zhu L, Delivopoulos E, et al. A microchannel neuroprosthesis for bladder control after spinal cord injury in rat. Sci Transl Med 2013; 5:210ra155.
Electrical Nerve Stimulation to Promote Micturition in Spinal Cord Injury Patients: A Review of Current Attempts 1
Jian Ren,1,2 Daniel J. Chew,3 Suzanne Biers,1 and Nikesh Thiruchelvam1* Department of Urology, Addenbrookes Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom 2 Department of Urology, China–Japan Friendship Hospital, Beijing, China 3 Department of Neurosciences, Addenbrookes Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom
Aims: In this review, we focus on the current attempts of electrical nerve stimulation for micturition in spinal cord injury (SCI) patients. Methods: A literature search was performed through PubMed using ‘‘spinal cord injury,’’ ‘‘electrical nerve stimulation AND bladder,’’ ‘‘sacral anterior root stimulation/stimulator’’ and ‘‘Brindley stimulator’’ from January 1975 to January 2014. Results: Twenty studies were selected for this review. Conclusion: Electrical nerve stimulation is a clinical option for promoting micturition in SCI patients. Well-designed, randomized and controlled studies are essential for further investigation. Neurourol. Urodynam. 35:365–370, 2016. # 2015 Wiley Periodicals, Inc. Key words: electrical nerve stimulation; neurogenic bladder; sacral anterior root stimulation; spinal cord injury INTRODUCTION
Normal bladder function depends on the integrity of central and peripheral nerve circuitry.1 This circuitry will be disrupted after spinal cord injury (SCI), leading to three main problems in bladder function: (i) detrusor-underactivity; (ii) detrusor-overactivity; and (iii) detrusor-sphincter dyssynergia (DSD).2 According to a UK consultation by questionnaire in 2010, only 21% of 142 SCI patients maintained normal voiding without the need for any other bladder management.3 In fact, most SCI patients will endure the devastating consequences of urinary retention, incontinence and infection. It will result in a poor quality of life (QoL) when the patients can not do clean intermittent selfcatheterization (CISC) but using indwelling transurethral or suprapubic catheter.3 It can also cause vesicoureteral reflux and damage to the upper urinary tract, even renal failure if left untreated for a long period. The Finetech-Brindley stimulator (Vocare1 system in USA), to our knowledge, is the only commercial functional electrical stimulation (FES) device applied clinically for micturition in SCI patients. It has been implanted in more than 2,000 individuals worldwide since 1970s. Although patients can use this equipment to empty their bladder, it seems that this procedure is not well accepted according to this relatively low number of implantations.4 It is important for clinicians and scientists to recognize the ways to improve the QoL, confidence and independence of patients suffering SCI.5 To gain an understanding of attempts to promote micturition in SCI patients, we have undertaken an expert review of electrical nerve stimulation in SCI patients. The aim of this review is to summarise current findings to date and stimulate debate and research in improving ways of enabling micturition among the SCI population. METHODS
A literature review was undertaken through a PubMed search by the primary author (JR) using the terms ‘‘spinal cord injury,’’ ‘‘electrical nerve stimulation AND bladder,’’ ‘‘sacral anterior root stimulation/stimulator’’ and ‘‘Brindley stimulator’’ from January 1975 to January 2014. The search was confined to additional filters, including having the abstract available, human species and in English. After reading the titles and abstracts, clinical #
2015 Wiley Periodicals, Inc.
papers directly relevant to electrical nerve stimulation for micturition in SCI patients were selected. Exclusion criteria were: (i) animal work; (ii) review paper; (iii) case report; and (iv) not relevant to bladder contraction, such as reports that only focused on the surgical techniques for implantation of the hardware or for detrusor overactivity. Manual inspection of the reference list of each selected article was performed to further identify studies that were not captured by the online search but that might be potentially relevant for the review. The second author (DC) and the senior author (NT) undertook a repeat search to ensure inclusion of all possible articles. Any question with regard to inclusion of a particular article, such as concern of bias or selective reporting, was resolved by discussion between the authors. As the number of clinical studies was low, bias was minimized by inclusion of all possible studies. This expert review was constructed by summarizing findings with presentation of results under thematic headings. The discussion was determined by expert consensus by the authors. RESULTS
The search resulted in 137 papers (see Fig. 1). After all abstracts were assessed and after relevant exclusion due to non-relevance, 25 full papers were accessed and reviewed. A further four papers were accessed following manual inspection. A further review of the identified 29 articles led to exclusion of nine papers. Those papers were excluded because: three of them focused on cost-effectiveness or QoL after implantation of the Finetech-Brindley system; one was focused only on the urodynamic result; the other five were relevant works undertaken by the same teams. There were two exceptions, Potential conflicts of interest: Nothing to disclose. Robert Pickard led the peer-review process as the Associate Editor responsible for the paper. Correspondence to: Nikesh Thiruchelvam, Department of Urology, Addenbrookes Hospital, Cambridge University Hospitals NHS Trust, Hills Road, Cambridge CB2 0QQ. E-mail: [email protected] Received 8 September 2014; Accepted 3 December 2014 Published online 8 February 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/nau.22730
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Fig. 1. Results of PubMed literature review (presented according to PRISMA additional records identified through reference sources (n ¼ 4).
one was a case report performed only through the pudendal nerve, and the other was the serial report performed by Brindley himself. Twenty full-text articles were assessed and summarized for this review. Some details were extracted from the papers and listed in Table I. Among these 20 studies, 14 were undertaken with the Brindley device,6–19 two used modified Brindley devices, which were the sacral anterior roots stimulation with anodal block20 and the Neurourology and Urodynamics DOI 10.1002/nau
sacral posterior and anterior roots stimulation (SPARS).21 Two used sacral neuromodulation,22,23 one with pudendal nerve,24 and one paper stimulated the whole or ventral sacral root.25 Sacral Anterior Root Stimulation and Sacral Deafferentation
The first application of a sacral anterior root stimulation (SARS) device was described and tested by GS Brindley in
Neurourology and Urodynamics DOI 10.1002/nau
30 500 47
12
10 96
35 23
5
Madersbacher, 1993 Brindley, 1994 Van Kerrebroeck, 1996
Rijkhoff,1998
Schurch, 1997 Egon, 1998
van der Aa, 1999 Creasey, 2001
Kirkham, 2002
13
29 137
Lombardi, 2009
Lombardi, 2009 Grasm€ ucke, 2013 (Epub)
55 months 14.8 4.8 years
Acute experiment 61 months
Sacral neuromodulation Sacral anterior roots
Sacral neuromodulation
Pudendal nerve trunk
Sacral posterior and anterior roots Sacral anterior roots
4 months 6.6 years
Sacral anterior roots Sacral anterior roots
0.25–12 years 1 year
Selective sacral anterior roots with anodal block Sacral anterior roots Sacral anterior roots
8 years 0.25–16 years 42.2 months Acute experiment 3.4 years 5.4–5.8 years
Sacral anterior roots Sacral anterior roots Sacral anterior roots
5–11 years 3–29 months
Stimulation site Sacral anterior roots Sacral anterior roots Sacral anterior roots The whole sacral root or sacral ventral roots Sacral anterior roots Sacral anterior roots
2–50 months 1–9 years – 6 years
Follow up
None 100%
None
None
94%
None
100% 100%
100% 100%
100%
100% 70% 100%
34% 100%
None 34% – 84%
Rhizotomy
66% 78%
69%
None
95%
20%
100% 78%
70% 89%
–
90% 86% 96%
82% 75%
100% 86% 73% 38%
Use for micturition
a
Other bladder management in those who use Electrical stimulation for micturition.
CSF, Cerebrospinal fluid; CIC, Clean intermittent catheterization; –, Date not reported or can not be concluded in the reference.
2
Yoo, 2007
440
50 12
Brindley, 1990 Sauerwein, 1990
Kutzenberger, 2005
11 50 22 19
Patients number
Brindley, 1982 Brindley, 1986 Robinson, 1988 Tanagho, 1989
Publications
TABLE I. Site of Stimulation and the Details From the Included References
4 patients with CIC, mean CISC number was 0.8 0.7 times daily – 22 condom catheters
–
3 with CIC 5 with CIC, 1 with indwelling catheter 3 with CIC, 1 with indwelling catheter –
– 10 with CIC
– 1 by CIC, 1 by indwelling catheter, 1 by abdominal straining 2 with Credes method – 4 patients with CIC 1 or 2 times daily –
– – – 1 with condom catheter
Combined bladder managementsa
– 62%
–
–
83%
–
84%
80% 89%
–
93% – 91%
77% 64%
59% 62% 68% 82%
Continence
None CSF leaks, 4 second deafferentation, implants removed CSF leaks, 3 receiver failures patients with stress incontinence
– 80 surgical revisions, 10 artificial sphincters, 4 second deafferentation
6 revisions for battery depletion
70 defects of the implant, 34 repair surgeries needed –
3 with persisting DSD
3 2 3 4
5 patients needed second rhizotomy 95 ops to remedy implants faults One implant infection needed remove, 3 second rhizotomy –
2 CSF leaks needed operation 14 CSF leaks 10 implant failures 6 DSD needed sphincterotomy 7 with pudendal neurotomy, 5 with levatorotomy 18 implant failures 1 CSF leak, 2 second rhizotomy needed
Main complications or other surgeries
Electrical Nerve Stimulation to Promote Micturition in SCI Bladder 367
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baboons in the 1970s, and then implanted in SCI patients in 1976. This device, which is now marketed as the FinetechBrindley stimulator, includes three intracorporeal components and an extracorporeal transmitter. The intracorporeal part has four slots, three cables and a receiver block. Each slot has three platinum foil electrodes. The external stimulator must be placed onto the position of the receiver block to evoke the device with low frequency (10–30Hz) waves. The electrodes can be placed intradurally or extradurally on the sacral roots S2-S4. For patients with intact EUS, electrical stimulation of the sacral roots especially in S3 and S4, generated contraction not only in the detrusor muscle but also in the EUS itself. If stimulation persisted, the sphincter permanently closed the bladder outlet and prevented micturition.6 In order to avoid this, an intermittent stimulation pattern was applied to induce poststimulus voiding. During the intermittent period (off stimulation), the striated muscle of EUS will relax immediately, but the detrusor smooth muscle undergoes a prolonged contraction emptying the bladder at a low pressure. Patients often need several courses of stimulation and subsequent flow to empty their bladder.26 Post-stimulus voiding by intermittent 30 Hz stimulation induced onto the sacral anterior roots allows the bladder to contract, while the sphincter undergoes periods of relaxation during the intermittent period to prevent dyssynergia. In order to eliminate the neurogenic detrusor overactivity, sacral deafferentation (SDAF) of the posterior roots of S2-S4/5 was applied.27 SDAF then became a routine procedure combined with SARS to improve bladder capacity, compliance and continence since the late 1980s. However, a severe consequence is that patients irreversibly lose their reflex erection and ejaculation in males and vaginal lubrication in females.28 It is important to note that this procedure demands surgical expertise for implantation, which may be another reason for the restricted use of this device. In 1986, Brindley reported implantation of the SARS in the first 50 patients.7 At the end of 1 to 9 years follow up, 43 patients still used the device regularly for micturition. In 91% (40/44) of patients, the residual volume of urine was less than 60 ml. Only two patients had deterioration of their upper urinary tract and four patients had three infections or more a year. Sacral deafferentation was not a routine step at that time, and only 10 patients underwent sacral posterior root rhizotomy. Another nine patients presented with increased bladder volume, and this may be partly attributed to the accidental injury of the posterior roots during implantation. From 1976 to 1992, Finetech-Brindley stimulators were implanted in 500 patients across 28 centers, mainly in the UK, Germany, France, Netherlands, New Zealand and Australia. After follow-up from 3 months to 16.1 years (mean 4 years), 411 patients still used their stimulators for micturition. 45 patients refrained from using the stimulator mainly because of weak detrusor responses. Most of them went back to CISC. Twentyone patients had died, due to circumstances unrelated to the device.12 Another large follow-up study was conducted by Kutzenbergen and colleagues, from 1986 to 2002. Of 440 SCI patients who received SARS/SDAF, 95% still used the device for micturition with a daily frequency of 4.7 times, and 83% maintained continence. Urinary tract infection (UTI) rates reduced from 6.3 to 1.2 times per year. Kidney function was € cke evaluated the results of stable.18 More recently, Grasmu SARS/SDAF by urodynamic tests. Among 137 patients, 107 (78%) were still using the device, the number of patients suffering from elevated detrusor pressure, low detrusor compliance, limited bladder capacity or incontinence were significantly reduced after implantation.19 Neurourology and Urodynamics DOI 10.1002/nau
Table I illustrates that most of the patients (70%–100%, when data available) would continue using their stimulator for micturition at the end of follow-up. Continence was also achieved in most of the reports were accompanied with SDAF, especially in the three larger studies.12,18,19 However, information on bladder management was not included in two of these three studies, and so we could not know exactly if the patients were completely free from clean intermittent catheterization (CIC) or used CIC as well as stimulation. Device faults and surgical revisions of the implants were the most common complications in long-term follow-ups. CSF leak became rare after the 1990s, possibly due to advancement of surgical technique. In the same period as Brindley’s 1970s studies, a team at the University of California, San Francisco evaluated the potential for evacuating the bladder by electrical stimulation of the bladder wall, pelvic nerve, spinal cord and sacral nerve29. Tanagho and colleagues reported 22 SCI patients with the stimulation of the whole sacral roots or the sacral ventral roots. However, the result was not satisfactory because only 38% of patients could use the stimulator for micturition. Half of patients needed pudendal neurotomy or levatorotomy even combined with rhizotomy, which were not common in the Brindley procedure.
Modification of the Finetech-Brindley Stimulator
As mentioned before, activation of the detrusor muscle was by accompanied stimulation induced DSD through the Brindley stimulator. Over the past 20 years, there have been a number of attempts to eliminate DSD or avoid rhizotomy for this procedure. In one acute experiment with 12 SCI patients during the implantation of a Finetech-Brindley stimulator combined with rhizotomy,20 the current through the larger nerve fiber was selectively blocked near the anodes due to the anodal current. This was achieved in eight patients. The sphincter was prevented from contraction with a 6.0 mA current, while the sphincter could also be switched on and off by a short duration current, which indicated that relaxation of the sphincter was not caused by fatigue nor damage to the nerve roots. However, anodal blocking could not be obtained in four patients. The author speculated that this could be due to excessive manipulation of the nerve roots during identification and electrode placing. Kirkham used the Finetech-Brindley device to set up SPARS in order to eliminate rhizotomy in an acute model.21 SPARS was implanted to the mixed sacral roots in five patients without rhizotomy. In three patients with postoperative bladder hyperreflexia, SPARS successfully inhibited hyperreflexia. Bladder contraction with a detrusor pressure more than 70 cm H2O could also be achieved by intense stimulation. However, DSD during the stimulation gap prevented the bladder from emptying. Only less than 50% amount of the urine was evacuated from the bladder.
Pudendal Nerve Stimulation
Pudendal nerve (PN) stimulation was conducted by a percutaneous catheter electrode in contact with the PN trunk. Two cases were tested acutely under this setting.24 In case 1, stimulation evoked a transient but relatively high (30 cm H2O) pressure. Urine leak could be achieved around the urethral catheter by repeated stimulation. In case 2, stimulation could only produce a low (9 cmH2O) bladder contraction, which did not result in effective voiding.
Electrical Nerve Stimulation to Promote Micturition in SCI Bladder Sacral Neuromodulation (SNM)
Lombardi reported the experience of SNM in 13 incomplete SCI patients with neurogenic non-obstructive urinary retention (NNOR).22 The SNM was permanently implanted 5.4 years (1–12 years) after the neurological diagnosis. Nine patients emptied their bladder completely by CIC before implantation, and the other four by Valsalva maneouver with increased residuals. Mean follow-up was 61 months (18–132 months). Nine (69%) patients were significantly improved by SNM, five of them no longer needed CISC, another four used mean CISC 0.8 0.7 times daily. Four patients were not improved after implantation due to detrusor underactivity. There were no major complications except for six revisions for battery depletion. However, a more recent study showed only 29 (38%) out of 77 incomplete SCI patients with N-NOR had a response to first stage SNM.23 Permanent implantation was performed in these patients. Nineteen (66%) patients were still responsive after 55 (6–107) months follow-up. Ten patients returned to baseline symptoms. The result was inconclusive because no effectiveness of the micturition by SNM and other bladder management were mentioned at the end point of the study. DISCUSSION
Regaining bladder function is the first shared priority of quadriplegics and paraplegics, even above the restoration of locomotion.30 Unfortunately, there is no simple solution to re-establishing and optimizing micturition for SCI patients. There is a lack of safe and effective drugs to treat bladder underactivity.31 Catheterization is a burden on the patient and has a social stigma affecting QoL,3 which is accompanied with a high prevalence of retrograde infection, urethral pain, haematuria and urethral stricture. Although it is the only commercial FES for bladder contraction until now, the Finetech-Brindley stimulator has not been well accepted across the world, when compared to the large numbers of patients with SCI who are catheter-dependent.4 The reason may be the unfamiliarity with this procedure by the patients and their doctors; fear of major spinal surgery, the prerequisition for and permanence of posterior root rhizotomy, and doubts about the effects of surgery. The cost of the Brindley device (42,803 euro in the first 12 months after implantation32) is a huge burden on healthcare providers and insurers, and prohibitive to patients in the poorer regions of the world. With respect to long term effectiveness and ease of use across a patient’s life time, complete and voluntary micturition by the Brindley procedure is much improved compared to conventional neurogenic bladder treatment.32 After implantation, the advantages of the Brindley procedure were reported as: reduction of infection rate (68%), improved social life (54%) and continence (54%), which were coincident with patients’ expectations, and accompanied with improved QoL.33 Despite advantages, defective stimulators or implants, inconvenience of leg spasms during stimulation, removal of infected implants and preference of other bladder emptying methods were the main reasons for no longer using the device.34 Refinement of the Finetech-Brindley system may advance re-uptake in the medical community. Subsequent DSD is still a big problem, and the results from this clinical review suggest its treatment is variable and inconclusive. SNM has some effect on bladder contraction without the need for rhizotomy. However, only preliminary data exists on this. Stimulation of the PN in animal models through different frequencies can achieve bladder contraction, EUS relaxation and stability of the detrusor muscle concurrently.35 This is a promising work, but the result of the only human test available was disappointing.24 Neurourology and Urodynamics DOI 10.1002/nau
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This review highlighted potential future avenues for research: (i) selective activation of the detrusor muscle, although excessively tested in animal model (data not shown) is too immature for clinical use; (ii) modification of the Finetech-Brindley stimulator to minimize the difficulty of implantation and complications; (iii) further study on other stimulation sites, for example, pudendal nerve stimulation; (iv) the mechanism of SNM on SCI-induced bladder dysfunction; and (v) combining available techniques with new strategies. This latter point may enable closed loop refinement in bladder electrical neuromodulation through recording bladder activity,36 whereby a stimulator or block will be reactive to the state of bladder fullness. CONCLUSION
Electrical nerve stimulation, mainly conducted with the Finetech-Brindley stimulator, is a considerable option for bladder management in SCI patients. However, there are as yet no randomized or controlled clinical trials, making it difficult to draw conclusions on optimal efficacy for neurogenic bladder treatment. Further work, both pre-clinically and clinically, is needed to refine neuromodulation treatment options for SCI patients. REFERENCES 1. Craggs MD, Balasubramaniam AV, Chung EAL, et al. Aberrant reflexes and function of the pelvic organs following spinal cord injury in man. Auton Neurosci Basic Clin 2006; 126–127:355–70. 2. Craggs MD. Pelvic somato-visceral reflexes after spinal cord injury: Measures of functional loss and partial preservation. Prog Brain Res 2006; 152:205–19. 3. Liu C-W, Attar KH, Gall A, et al. The relationship between bladder management and health-related quality of life in patients with spinal cord injury in the UK. Spinal Cord 2010; 48:319–24. 4. Wein AJ. Re: Quality of life in complete spinal cord injury patients with a brindley bladder stimulator compared to a matched control group. J Urol 2013; 189:613. 5. French JS, Anderson-Erisman KD, Sutter M. What do spinal cord injury consumers want? A review of spinal cord injury consumer priorities and neuroprosthesis from the 2008 neural interfaces conference. Neuromodulation J Int Neuromodulation Soc 2010; 13:229–31. 6. Brindley GS, Polkey CE, Rushton DN. Sacral anterior root stimulators for bladder control in paraplegia. Spinal Cord 1982; 20:365–81. 7. Brindley GS, Polkey CE, Rushton DN, et al. Sacral anterior root stimulators for bladder control in paraplegia: The first 50 cases. J Neurol Neurosurg Psychiatry 1986; 49:1104–14. 8. Robinson LQ, Grant A, Weston P, et al. Experience with the Brindley anterior sacral root stimulator. Br J Urol 1988; 62:553–7. 9. Brindley GS, Rushton DN. Long-term follow-up of patients with sacral anterior root stimulator implants. Paraplegia 1990; 28:469–75. 10. Sauerwein D, Ingunza W, Fischer J, et al. Extradural implantation of sacral anterior root stimulators. J Neurol Neurosurg Psychiatry 1990; 53:681–4. 11. Madersbacher H, Fischer J. Sacral anterior root stimulation: prerequisites and indications. Neurourol Urodyn 1993; 12:489–94. 12. Brindley GS. The first 500 patients with sacral anterior root stimulator implants: General description. Paraplegia 1994; 32:795–805. 13. Van Kerrebroeck PE, Koldewijn EL, Rosier PF, et al. Results of the treatment of neurogenic bladder dysfunction in spinal cord injury by sacral posterior root rhizotomy and anterior sacral root stimulation. J Urol 1996; 155: 1378–81. 14. Schurch B, Rodic B, Jeanmonod D. Posterior sacral rhizotomy and intradural anterior sacral root stimulation for treatment of the spastic bladder in spinal cord injured patients. J Urol 1997; 157:610–4. 15. Egon G, Barat M, Colombel P, et al. Implantation of anterior sacral root stimulators combined with posterior sacral rhizotomy in spinal injury patients. World J Urol 1998; 16:342–9. 16. Van der Aa HE, Alleman E, Nene Snoek AG. Sacral anterior root stimulation for bladder control: clinical results. Arch Physiol Biochem 1999; 107:248–56. 17. Creasey GH, Grill JH, Korsten M, et al. An implantable neuroprosthesis for restoring bladder and bowel control to patients with spinal cord injuries: A multicenter trial. Arch Phys Med Rehabil 2001; 82:1512–9. 18. Kutzenberger J, Domurath B, Sauerwein D. Spastic bladder and spinal cord injury: Seventeen years of experience with sacral deafferentation and implantation of an anterior root stimulator. Artif Organs 2005; 29:239–41.
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19. Grasm€ ucke D, Krebs J, van Ophoven A, et al. Urodynamic results, clinical efficacy, and complication rates of sacral intradural deafferentation and sacral anterior root stimulation in patients with neurogenic lower urinary tract dysfunction resulting from complete spinal cord injury. Neurourol Urodyn 2013; doi:10.1002/nau.22486 20. Rijkhoff NJ, Wijkstra H, van Kerrebroeck PE, et al. Selective detrusor activation by sacral ventral nerve-root stimulation: results of intraoperative testing in humans during implantation of a Finetech-Brindley system.. World J Urol 1998; 16:337–41. 21. Kirkham APS, Knight SL, Craggs MD, et al. Neuromodulation through sacral nerve roots 2 to 4 with a Finetech-Brindley sacral posterior and anterior root stimulator. Spinal Cord 2002; 40:272–81. 22. Lombardi G, Del Popolo G. Clinical outcome of sacral neuromodulation in incomplete spinal cord injured patients suffering from neurogenic lower urinary tract symptoms. Spinal Cord 2009; 47:486–91. 23. Lombardi G, Musco S, Celso M, et al. Intravesical electrostimulation versus sacral neuromodulation for incomplete spinal cord patients suffering from neurogenic non-obstructive urinary retention. Spinal Cord 2013; 51:571–8. 24. Yoo PB, Klein SM, Grafstein NH, et al. Pudendal nerve stimulation evokes reflex bladder contractions in persons with chronic spinal cord injury. Neurourol Urodyn 2007; 26:1020–3. 25. Tanagho EA, Schmidt RA, Orvis BR. Neural stimulation for control of voiding dysfunction: a preliminary report in 22 patients with serious neuropathic voiding disorders. JURO 1989; 142:340–5. 26. Brindley GS. An implant to empty the bladder or close the urethra. J Neurol Neurosurg Psychiatry 1977; 40:358–69.
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27. Sauerwein D. Funktionelle Elektrostimulation der Harnblase: Erste Erfahrungen mit sakraler Deafferentation und Vorderwurzelstimulation nach Brindley in Deutschland. Verh Dtsch Ges Urol 1988; 39:595–7. 28. Ragnarsson KT. Functional electrical stimulation after spinal cord injury: Current use, therapeutic effects and future directions. Spinal Cord 2008; 46:255–74. 29. Schmidt RA. The winding path to sacral foramen neural modulation: A historic chronology. Int Urogynecology J 2010; 21 Suppl:S431–8. 30. Anderson KD. Targeting recovery: Priorities of the spinal cord-injured population. J Neurotrauma 2004; 21:1371–83. 31. Andersson K-E. Bladder underactivity. Eur Urol 2014; 65:399–401. 32. Benard A, Verpillot E, Grandoulier AS, et al. Comparative cost-effectiveness analysis of sacral anterior root stimulation for rehabilitation of bladder dysfunction in spinal cord injured patients. Neurosurgery 2013; 73:600–8. Discussion 608. 33. Vastenholt JM, Snoek GJ, Buschman HP, et al. A 7-year follow-up of sacral anterior root stimulation for bladder control in patients with a spinal cord injury: Quality of life and users experiences. Spinal Cord 2003; 41:397–402. 34. Martens FMJ, den Hollander PP, Snoek GJ, et al. Quality of life in complete spinal cord injury patients with a Brindley bladder stimulator compared to a matched control group. Neurourol. Urodyn. 2011; 30:551–5. 35. Yang G, Wang J, Shen B, et al. Pudendal nerve stimulation and block by a wireless-controlled implantable stimulator in cats. Neuromodulation 2014;17:490–6. 36. Chew DJ, Zhu L, Delivopoulos E, et al. A microchannel neuroprosthesis for bladder control after spinal cord injury in rat. Sci Transl Med 2013; 5:210ra155.
