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Initial Experience with Sacral Nerve Stimulation as a Treatment for Intractable Urge Incontinence
INITIAL EXPERIENCE WITH SACRAL NERVE STIMULATION AS A TREATMENT FOR INTRACTABLE URGE INCONTINENCE Jeffrey M. Mangel, MD, FRCSC, I John W. Spurlock, MD, FACOG I 1
Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, St. Luke's Hospital, Bethlehem, Pennsylvania
Abstract Objective: To evaluate the efficacy of sacral nerve stimulation using a permanent implantable system in the treatment of intractable urge incontinence, urgency, frequency, and nocturia. Methods: Ten women with varying degrees of urinary urge incontinence, urgency, frequency, and nocturia were implanted with an Interstim® sacral nerve stimulation device. To be eligible for the implant, subjects must have failed biofeedback and pelvic electrical stimulation therapy and at least two anticholinergic drugs. These women had tried at least two of tolterodine, oxybutynin, and imipramine. They then underwent a three to seven day test stimulation involving the placement of a temporary electrode into the S3 foramen, one on each side, attached to a portable external stimulation device. During this period, all subjects kept a voiding diary and noted their number of incontinent episodes, pads used, and symptoms of urgency, frequency, and nocturia. If at least a 50 percent improvement was noted, both objectively and subjectively, the subjects were offered a permanent implant. All procedures were done in the operating room and involved the placement of a permanent electrode into the S3 foramen on one side through a small (5-7 cm) vertical incision over the sacrum. The electrode body was tunneled under the skin and connected to the stimulating device implanted in the upper buttock through a second horizontal incision. Subjects have been followed for an average of 12.2 months (range 7-16 months). Results: The average age of the subjects was 55.1 years (range 30-76 years). All 10 subjects experienced a marked decrease in urge incontinence, urgency, frequency, and nocturia. Eight subjects currently experience no incontinent episodes and are no longer using pads; the other two use only one pad per day. All were using at least four pads daily prior to the implant. All now describe their urgency as "appropriate." Pre-implant urgency descriptions included "moderate," "constant," and "strong" in two, one, and seven subjects respectively. Frequency in all is at least two hours, and reaches four hours in five subjects. Nine of the subjects voided every hour before the implant. Eight subjects experienced three or more episodes of nocturia before the implant; three now void twice
KeyWords Urinary incontinence, overactive bladder, sacral nerve stimulation, Interstim®, pelvic floor dysfunction Competing interests: none declared Received on November 22nd, 2000. Revised and accepted on June 7th, 200 I. JOGe
per night, while the rest get up either once or not at all. Interestingly, one subject who also suffered from fecal incontinence was cured by this therapy. Another subject with a long history of chronic constipation and an average of one bowel movement per week now moves her bowels daily. All 10 subjects reported satisfaction and responded yes to having this procedure again. There were no adverse effects reported. Conclusions: Sacral nerve stimulation is a promising new therapy for women with intractable urge incontinence and associated urgency, frequency, and nocturia. It appears to be both safe and efficacious. Long term studies with larger numbers of subjects will determine its ultimate place in the management of the overactive bladder. The potential role of sacral nerve stimulation in women with bowel dysfunction and pelvic pain also needs to be investigated.
Resume Objectif : Evaluer I'efficacite de la stimulation des nerfs sacres au moyen d'un systeme permanent implantable pour Ie traitement de I'incontinence a I'effort, du besoin imperieux, de la pollakiurie et de la nocturie refractaires. Methode: On a implante Ie dispositif de stimulation des nerfs sacres Interstim® chez dix femmes souffrant, a divers degres, de mictions imperieuses, de besoin imperieux, de pollakiurie et de nocturie. Pour pouvoir recevoir cet implant, les sujets devaient avoir suivi, sans succes, une therapie de stimulation electrique du pelvis et de retroaction (biofeedback) et avoir pris au moins deux medicaments anticholinergiques. Ces dix femmes avaient pris au moins deux des trois medicaments suivants : la tolterodine, I'oxybutynine et I'imipramine. Elles ont alors subi un test de stimulation allant de trois a sept jours pendant lequel on a place deux electrodes temporaires dans I'orifice S3, une de chaque cote, reliees a un appareil portatif externe de stimulation. Pendant cette periode, chaque sujet a note, dans un carnet personnel, chaque miction, chaque incident d'incontinence, Ie nombre de serviettes hygieniques utilisees ainsi que les symptomes de besoin imperieux, de pollakiurie et de nocturie. Si on a constate, objectivement et subjectivement, une amelioration d'au moins 50 pour cent, on a offert aux sujets d'installer un implant permanent. Toutes les interventions ont ete faites en salle d'operation. On a place une electrode permanente d'un cote de I'orifice S3 apres avoir fait une petite incision verticale (de 5 a 7 cm) sur Ie sacrum. Le corps de I'electrode a ete glisse sous la peau et branche a un dispositif de stimulation implante dans la partie superieure de la fesse au moyen d'une seconde incision. Les sujets ont ete suivis, en moyenne, pendant 12,2 mois (de 7 a 16 mois).
AUGUST 2001
Resultats : L'age moyen des sujets etait de 55,1 ans (de 30 it 76 ans). Tous les sujets ont connu une baisse importante des mictions imperieuses, du besoin imperieux, de la pollakiurie et de la nocturie. Huit femmes n'ont maintenant plus d'incidents d'incontinence et ne portent plus de serviettes hygieniques ; les deux autres n'en utilisent qu'une par jour. Chacune de ces femmes utilisait au moins quatre serviettes par jour avant la pose de I'implant. Chacune d'elles decrit maintenant son besoin imperieux comme {( adequat ». La description du besoin imperieux avant I'intervention comprenait : {( modere » (2 sujets), {( constant» (un sujet) et {( fort» (sept sujets). La frequence est maintenant d'au moins deux heures chez chacune des femmes et, chez cinq d'entre elles, elle atteint quatre heures. Neuf d'entre elles urinaient toutes les heures avant I'implant et huit avaient trois episodes ou plus de nocturie. La plupart d'entre elles ne doivent maintenant uriner qu'une fois par nuit. II est aussi interessant de noter qu'une des participantes qui souffrait aussi d'incontinence anale a ete guerie a la suite de cette therapie. Une autre, qui avait de longs antecedents de constipation chronique et qui n'avait des selles qu'une fois par semaine en moyenne, a maintenant des selles quotidiennes. Chacune des dix femmes a indique sa satisfaction et a repondu {( oui » a la question de savoir si elle accepterait encore d'ihre traitee par cette technique. Aucun effet secondaire n'a ete constate. Conclusions: La stimulation des nerfs sacres est une nouvelle therapie prometteuse pour les femmes dont I'incontinence imperieuse ainsi que Ie besoin imperieux, la frequence et la nocturie qui y sont lies, sont refractaires. Cette technique semble a la fois securitaire et efficace. II faudra mener des etudes a long terme portant sur un plus grand nombre de sujets pour en definir Ie role definitif pour Ie traitement de la vessie hyperactive. II faudra aussi examiner Ie role possible de la stimulation des nerfs sac res chez les femmes souffrant de troubles intestinaux et de douleurs pelviennes.
J Obstet
Gynaecol 200 I;23(8):667-72
Sacral nerve stimulation is proposed as a new therapy for consideration by women with urge incontinence who have failed standard therapies. Its mechanism of action remains unclear. Sacral nerve stimulation is thought to involve modulation of various neural pathways, resulting in enhancement of inhibitory impulses to the detrusor muscle. 15,16 It may decrease spasticity of the pelvic floor by converting fast-twitch fibres to slow-twitch ones, or by interrupting chronically established pathologic reflex arcs. It may work in a manner similar to cardiac pacemakers by delivering constant or intermittent impulses, thereby overriding nervous control of the bladder. We report our initial experience with sacral nerve stimulation in women with intractable urge incontinence. MATERIALS AND METHODS ,
Women were recruited from the Continence Management Institute of St. Luke's Hospital, a urogynaecologic referral practice, between December 1998 and December 1999. To be eligible for sacral nerve stimulation therapy, the women had to have failed conservative therapy and at least two anticholinergic medication trials. All subjects had urge incontinence with varying degrees of urgency, frequency, and nocturia. Subjects underwent a complete history and physical examination, uroflowmetry, urinalysis, and a post-void residual determination by ultrasound. Subjects also kept a three day voiding diary prior to their initial visit. Women with neurological conditions, post-void residuals greater than 100 cc or who had demonstrable stress urinary incontinence with a comfortably full bladder were excluded. Test stimulation was done in the office under local anesthesia (Figure 1), and involved the placement of temporary electrodes into S3 foramen bilaterally, attached to a portable external FIGURE I
INTRODUCTION
TEST STIMULATION
Fifteen to 30 percent of women over the age of 65 in the United States are incontinent. l The annual cost to care for women with urinary incontinence is estimated at $11.2 billion (US D) in the community and $5.2 billion in nursing homes. l Urinary urge incontinence is particularly distressing for many women, as urine leakage is often unpredictable and can be of large volume. Women with urge incontinence often have additional symptoms of frequency, nocturia, and occasionally enuresis that can be debilitating and lead to social isolation. Standard treatment for urge incontinence includes behavioural therapy,2,3 dietary modification,4 pelvic muscle exercises,5 biofeedback,5,6 pelvic floor electrical stimulation,7,8 and the use of various medications. 9-11 While many women respond well to these therapies, 15 to 40 percent are either refractory or do not reach their goals of improvement. 12, 13 Previously, these women were left to either live with their symptoms or to consider a major surgical intervention such as augmentation cystoplasty. 12,14 JOGC
AUGUST 2001
stimulation device. Stimulation of the S3 nerve produces a characteristic levator ani contraction, which manifests as a "bellowing" of the vagina and rectum. The stimulated S3 nerve also causes flexion of the great toe. These signs, along with the patient's reporting of a sensation of pulling in the vagina and rectum, are used to confirm correct placement of the electrodes. Twenty-one women with intractable urge incontinence underwent a three to seven day test stimulation. 17,18 The range of duration for each test was based on when each woman would return to the office for subsequent follow-up, with no difference in test success based on its duration. Subjects completed a detailed voiding diary for three days immediately prior to and then throughout the test period. The diary contained information on episodes of incontinence and pad use, as weJJ as symptoms of urgency, frequency, and nocturia. Stimulation was always unilateral, but subjects were instructed to switch sides about halfWay through the test period and document on their diaries when they did so. The test stimulation was considered positive if the woman had at least a 50 percent improvement, both objectively and subjectively; in her symptoms. Those women who had positive test stimulations were then offered a permanent implant. Thirteen out of21 women (62%) had positive test stimulations, and 10 decided to have the implant. This procedure was done in the operating room under general anesthesia without neuromuscular blockade (Figure 2). A permanent electrode was placed in the S3 foramen on one side through a small (5-7 cm) vertical incision over the sacrum. The side that was found to be more effective during the test stimulation was usually chosen. Localization of the S3 nerve was accomplished in a manner similar to that described for the test stimulation. The electrode was secured to the sacrum with a bone anchor. The electrode body FIGURE 2 PERMANENT IMPLANT
was then tunneled underneath the skin and connected to the stimulating device implanted in the upper buttock through a second small (5-7 em) horizontal incision. The stimulating device was usuaJJy implanted on the woman's dominant side. Subjects remained in hospital overnight. They returned to the office one to two weeks post-operatively to have the device turned on and programmed. The subjects have been followed for an average of 12.2 months (range 7-16 months). To be eligible for sacral nerve stimulation, all subjects underwent weekly outpatient treatments of pelvic muscle reeducation, biofeedback, and pelvic floor electrical stimulation for six to 12 weeks. These 30 minute treatments were carried our in our office by trained nurses and included dietary modification, bladder retraining, and a bowel program if appropriate. All women who had previously demonstrated levator muscle weakness were able to isolate and improve pelvic floor elevation after this therapy. In addition, all women had trials of at least two of tolterodine, oxybutynin or imipramine. Medications were discontinued in all cases either because of a lack of efficacy or due to unwanted side effects, particularly dry mouth. RESULTS
The average duration of bladder symptoms was 6.8 years (range 2.1 to 20.0 years). One woman had a successfullaparoscopic Burch procedure at a different institution for stress urinary incontinence approximately one year prior to presentation. No other subjects had undergone previous incontinence surgery. Physical examinations were unremarkable except for weakness of the levator ani muscles in seven women initially, associated with an inability to significantly elevate the pelvic floor on demand. Interestingly, these women reported having done Kegel exercises in the past. None of the women had demonstrable stress incontinence or any significant pelvic organ prolapse. Uroflowmetry revealed decreased mean flow rates (less than 10 cclsec) in three women with straining patterns. All FIGURE) PAD USE . .. . ,'
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nl Ilmpl nl
women had post-void residual urine volumes less than 100 cc and negative urinalyses. The average age of the 10 women who chose the permanent implant was 55.1 years (range 30-76 years). All women were using at least four pads daily before the implant (Figure 3). The average follow-up for the implanted women was 12.2 months (range 7-16 months). Three women who had positive tests chose not to pursue the permanent implant. Two of these women had interstitial cystitis and opted for continued medical therapy and periodic bladder instillations. The other had chronic constipation, averaging one bowel movement per week. During the test period, she had daily bowel movements, bur did not want her bowel function to change. All 10 women had a marked improvement in their bladder symptoms as determined by their histories and voiding diaries. In all cases, the improvement with the permanent implant was at least as good or better than the results of the test stimulation. Eight women were completely continent after the implant and no longer used pads; the other two used only one pad per day. Prior to and after the surgical implantation, subjects were asked to describe their sensations of urgency from a list of several descriptive words (Table 1). All now label their urgency as "appropriate." Preimplant descriptions included "moderate," "constant," and "strong" in two, one, and seven women respectively. All women subjectively reported that they are now able to postpone voiding, whereas eight were unable to do this prior to the implant. Nine patients voided at least every hour prior to the implant. On post-implant assessment, all were able to hold at least two hours, and five women were able to hold four hours between voiding episodes (Figure 4). The mean number of voids per 24 hours decreased from 16.2 (range 6-25) to 8.4 (range 5-12) (p < 0.001). Nocturia was also reduced by the implant. Prior to surgery, eight women had at least three episodes of nocturia before surgery. After surgery, three women awakened twice per night on average to void post-implant; the rest got up either once or not at all (Figure 5). Several other clinical observations were noted. One woman who complained of fecal incontinence pre-operatively was cured by the implant. Another woman with a history of
r GURE .. URINARY FREQUENCY
o
chronic constipation and an average of one bowel movement per week now moves her bowels daily. Three out of the 10 women had cystoscopically diagnosed interstitial cystitis, and all three have achieved substantial improvement in their symptoms. One of these women turned the unit off for several days to undergo an unrelated surgical procedure, approximately one year after she had received the implant. Her irritative bladder symptoms returned almost immediately, and were then corrected again after the device was turned back on. There were no major complications during this study. All subjects were discharged on the first post-operative day withour incident. At time of writing, all women were still using the implant, although one woman is considering having it removed because of discomfort over the generator site when she sits. Her symptoms remain well controlled, however. There has not been any reduction in bladder control over time, and all subjects continue to be followed every three to six months.
FIGURE S NOCTURIA
e
TABLE I
URINARY URGENCY: DESCRIPTIVE WORDS • None • Appropriate • Mild • Moderate • Strong • Constant
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AUGUST 2001
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DISCUSSION
Urinary urge incontinence remains a challenging problem for both patients and clinicians. Standard behavioural and pharmacological therapies fail to provide adequate symptom control in 15 to 40 percent of women suffering from urge incontinence. l2 •l3 Among those women in whom standard treatments had failed, sacral nerve stimulation produced excellent therapeutic results. The pathophysiology of urge incontinence and overactive bladder is poorly understood, but may involve sacral neuropathy. 15.16 It is thus not surprising that a therapy targeting sacral nerves rather than the bladder might provide a dramatic improvement in symptoms. There do not seem to be any parameters in a patient's history, physical examination or investigations that predict positivity of the sacral nerve stimulation test procedure: 50 to 60 percent of women with urge incontinence will test positive.14.19-21 Patients either experience a dramatic reduction in urge incontinence, pad use, nocturia, and voids per day, or virtually no change at all. It is possible that poor lead placement or lead migration during the test may in part explain why some patients have little to no improvement. 20.21 As our understanding of how sacral nerve stimulation works in this setting is theoretical, it is not surprising that some women with overactive bladder symptoms and urge incontinence would be refractory to this therapy. As a routine, we did not carry out multichannel urodynamic testing in our patients prior to test stimulation or the surgical implant procedure. There are several reasons for this. First, the presence or absence of detrusor instability has no bearing on the management of a woman with purely overactive bladder symptoms.22,23 Such a woman is a candidate for conservative treatment or pharmacological therapy based on her hisrory, physical examination, voiding diary, normal uroflowmetry, normal post-void residual measurement, and negative urinalysis. Second, demonstrable detrusor instability on urodynamic testing is of no help in predicting success or failure with sacral nerve stimulation therapy.19 To our knowledge, the only reliable pre-operative indicator of sacral nerve stimulation efficacy is a positive test stimulation. While we do not discount the value of extensive testing in some women with overactive bladders, the results of any further work-up or urodynamic testing were unlikely to have influenced their management. We do acknowledge that pre- and post-implant urodynamics could have been useful in elucidating how sacral nerve stimulation affects various bladder parameters. We did not routinely offer cystoscopy as part of our evaluation unless the woman had hemaruria on urinalysis, in the absence of infection. Five women in our series, however, did undergo cystoscopic evaluation. Three women with interstitial cystitis were successfully treated by sacral nerve stimulation, suggesting sacral nerve stimulation to be an important treatment option for women with this chronic and often debilitating condition. Two other JOGC
women had normal cystoscopies. Since a prerequisite for sacral nerve stimulation is urge incontinence refractory to standard treatment, many such women will be suspicious for interstitial cystitis and will undergo cyStoscopy. This is particularly true in younger women with a longstanding history of irritative bladder symptoms. These women may wish to try other therapies, such as pentosan polysulfate (Elmiron®) or bladder instillations, prior to considering sacral nerve stimulation. It is reasonable, however, to proceed directly to a test stimulation in such patients, since confirming the diagnosis of interstitial cystitis is not predictive of success or failure with this therapy. If the woman has a positive test, our experience suggests a permanent implant will dramatically improve her bladder symptoms regardless of the findings at cystoscopy. While it is possible that certain conditions, such as bladder tumours, stones, and sutures from prior surgeries may have been missed by not performing cystoscopy routinely, we feel that this is highly unlikely. Such patients would not be expected to benefit from sacral nerve stimulation, since the pathophysiology is unrelated to their sacral nervous system. We question the likelihood of discovering these anatomical findings in the face of a normal urinalysis. The unexpected finding in our study of improved bowel function in two women, one with fecal incontinence and the other with chronic constipation, raises interesting questions regarding other potential indications for sacral nerve stimulation. It is possible that the pathophysiology of chronic bowel dysfunction, like that of urge incontinence, may be a result of worsening sacral neuropathy. It is biologically plausible that the sacral nervous system of a woman with chronic constipation might stimulate the distal colon and rectum. Many women with urge incontinence and overactive bladder also suffer from poor bowel motility and incomplete fecal evacuation. Similarly, fecal incontinence, in the face of an anatomically normal anal sphincter, may be explained by abnormal sacral nerve impulses or aberrant reflex pathways to the rectum and anus. It would be reasonable to suggest that modulation of these impulses may therefore improve both bladder and bowel function. This finding requires further study. We have not seen the same rate oflead migration with the permanent implant that has been reported by other groups,20.21 and did not have to reoperate on any of the women in our study. It is possible that our approach of securing the electrode to the sacrum with a bone anchor may reduce the incidence of migration. Further, in our study, intraoperative fluoroscopy was used in addition to anatomical landmarks and characteristic motor responses, to confirm lead placement. This study is limited by the small number of subjects, the lack of a control group, and the unblinded nature of the intervention for both the subjects and the investigators. Blinding the subjects would be difficult to achieve, as we believe it unethical to carry out a sham surgical procedure. It is, however, an encouraging initial experience with a new therapy that has potential AUGUST 2001
application to several pelvic floor disorders. Further study is warranted to investigate the role of sacral nerve stimulation therapy in the treatment of refractory urge incontinence. CONCLUSION
Sacral nerve stimulation is a promising new therapy for women with intractable urge incontinence and associated urgency, frequency, and nocturia. It appears to be both safe and efficacious. Long term studies with larger numbers of subjects will determine its ultimate place in the management of the overactive bladder. The potential role of sacral nerve stimulation in women with bowel dysfunction and pelvic pain also needs to be investigated. REFERENCES I.
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United States Department of Health and Human Services. Urinary Incontinence in Adults:Acute and Chronic Management. Public Health Service.Agency for Health Care Policy and Research:AHCPR Publication No. 96-0682. March 1996. Fantl )A.Wyman)F. McClish OK. Harkins Sw. Elswick RK.Taylor JR. et al. Efficacy of bladder training in older women with urinary incontinence. JAm Med Assoc 1991 ;265:609-13. Jarvis GJ. and Millar DR. Controlled trial of bladder drill for detrusor instability. Br Med J 1980;281 :322-33. Weinberger MW. Goodman BM. Carnes M. Long-term efficacy of nonsurgical urinary incontinence treatment in elderly women.J Gerontol A Bioi Sci Med Sci I999;54(3):M 117-21. Wyman JF. Fantl JA. McClish OK. Bump RC. Comparative efficacy of behavioral interventions in the management of female urinary incontinence. Continence Program for Women Research Group.Am J Obstet Gynecol 1998; 179(4):999-1 007. Burgio KL. Locher JL. Goode PS. Hardin JM. McDowell BJ. Dombrowski M. et al. Behavioral vs. drug treatment for urge urinary incontinence in older women: a randomized controlled trial. JAm Med Assoc 1998;280(23): 1995-2000. Brubaker L. Benson JT. Bent A, ClarkA, Shott S.Transvaginal electrical stimulation for female urinary incontinence.Am J Obstet Gynecol 1997; 177(3):536-40. Caputo RM. Benson JT. McClellan E. Intravaginal maximal electrical stimulation in the treatment of urinary incontinence.J Repro Med 1993;38(9):667-71. Abrams P, Freeman R.Anderstrom C. Mattiasson A. Tolterodine. a new anti muscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Br J Urol 1998;81 (6): 80 I-I O. Goldenberg MM.An extended-release formulation of oxybutynin chloride for the treatment of overactive urinary bladder. Clin Ther 1999;21 (4): 634-42. Appell RA. Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis. Urol I997;50(Suppl GA):90-6. Clinical Practice Guideline: Urinary Incontinence in Adults. Rockville. Maryland: US Department of Health and Human Services. 1992; pp.38-43. National Association for Continence (NAFC). Consumer Focus '96: A Survey of Community Dwelling Incontinent People. 1996. Bosch JL. Groen J. Sacral (S3) segmental nerve stimulation as a treatment for urge incontinence with detrusor instability: results of chronic electrical stimulation using an implantable neural prosthesis. J Urol 1995; 154:504-7. Thon WF. Baskin LS.Jonas U. Tanagho EA, Schmidt RA. Neuromodulation of voiding dysfunction and pelViC pain. World J Urol 1991 ;9: 138-41.
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16. Bosch R. Groen J. Effects of sacral segmental nerve stimulation on urethral resistance and bladder contractility: how does neuromodulation work in urge incontinence patients! Neurourol Urodynam 1995; 14: 502. 17. Schmidt RA. Senn E.Tanagho EA. Functional evaluation of sacral nerve root integrity: report of a technique. Urol 1990;35:388-92. 18. Siegel SW Management of voiding dysfunction with an implantable neuroprosthesis. Urol Clin N Am 1992; 19: 163-70. 19. Koldewijn EL. Rosier PF. Meuleman EJ. Koster AM. Debruyne FM. van Kerrebroeck PE. Predictors of success with neuromodulation in lower urinary tract dysfunction: results of trial stimulation in 100 patients. J Urol 1994; 152: 2071-5. 20. Janknegt RA.Weil EH. Eerdmans PH. Improving neuromodulation technique for refractory voiding dysfunctions: two-stage implant. Urol 1997;49:358-62. 21. Schmidt RA.Jonas U. Oleson KA.Janknegt RA. Hassouna MM. Siegel Sw. et al. Sacral nerve stimulation for the treatment of refractory urinary urge incontinence.) Urol 1999;162:352-7. 22. Karram MM. Partoll L. Rahe J. Efficacy of nonsurgical therapy for urinary incontinence.J Repro Med 1996;41 (4):215-9. 23. Wyman JF. Fantl JA. McClish OK. Harkins Sw. Uebersax JS. Ory MG. Quality of life following bladder training in older women with urinary incontinence.lnt Urogynecol J Pelvic Floor Dysfn 1997;8(4):223-9.
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Abstract Objective: To evaluate the efficacy of sacral nerve stimulation using a permanent implantable system in the treatment of intractable urge incontinence, urgency, frequency, and nocturia. Methods: Ten women with varying degrees of urinary urge incontinence, urgency, frequency, and nocturia were implanted with an Interstim® sacral nerve stimulation device. To be eligible for the implant, subjects must have failed biofeedback and pelvic electrical stimulation therapy and at least two anticholinergic drugs. These women had tried at least two of tolterodine, oxybutynin, and imipramine. They then underwent a three to seven day test stimulation involving the placement of a temporary electrode into the S3 foramen, one on each side, attached to a portable external stimulation device. During this period, all subjects kept a voiding diary and noted their number of incontinent episodes, pads used, and symptoms of urgency, frequency, and nocturia. If at least a 50 percent improvement was noted, both objectively and subjectively, the subjects were offered a permanent implant. All procedures were done in the operating room and involved the placement of a permanent electrode into the S3 foramen on one side through a small (5-7 cm) vertical incision over the sacrum. The electrode body was tunneled under the skin and connected to the stimulating device implanted in the upper buttock through a second horizontal incision. Subjects have been followed for an average of 12.2 months (range 7-16 months). Results: The average age of the subjects was 55.1 years (range 30-76 years). All 10 subjects experienced a marked decrease in urge incontinence, urgency, frequency, and nocturia. Eight subjects currently experience no incontinent episodes and are no longer using pads; the other two use only one pad per day. All were using at least four pads daily prior to the implant. All now describe their urgency as "appropriate." Pre-implant urgency descriptions included "moderate," "constant," and "strong" in two, one, and seven subjects respectively. Frequency in all is at least two hours, and reaches four hours in five subjects. Nine of the subjects voided every hour before the implant. Eight subjects experienced three or more episodes of nocturia before the implant; three now void twice
KeyWords Urinary incontinence, overactive bladder, sacral nerve stimulation, Interstim®, pelvic floor dysfunction Competing interests: none declared Received on November 22nd, 2000. Revised and accepted on June 7th, 200 I. JOGe
per night, while the rest get up either once or not at all. Interestingly, one subject who also suffered from fecal incontinence was cured by this therapy. Another subject with a long history of chronic constipation and an average of one bowel movement per week now moves her bowels daily. All 10 subjects reported satisfaction and responded yes to having this procedure again. There were no adverse effects reported. Conclusions: Sacral nerve stimulation is a promising new therapy for women with intractable urge incontinence and associated urgency, frequency, and nocturia. It appears to be both safe and efficacious. Long term studies with larger numbers of subjects will determine its ultimate place in the management of the overactive bladder. The potential role of sacral nerve stimulation in women with bowel dysfunction and pelvic pain also needs to be investigated.
Resume Objectif : Evaluer I'efficacite de la stimulation des nerfs sacres au moyen d'un systeme permanent implantable pour Ie traitement de I'incontinence a I'effort, du besoin imperieux, de la pollakiurie et de la nocturie refractaires. Methode: On a implante Ie dispositif de stimulation des nerfs sacres Interstim® chez dix femmes souffrant, a divers degres, de mictions imperieuses, de besoin imperieux, de pollakiurie et de nocturie. Pour pouvoir recevoir cet implant, les sujets devaient avoir suivi, sans succes, une therapie de stimulation electrique du pelvis et de retroaction (biofeedback) et avoir pris au moins deux medicaments anticholinergiques. Ces dix femmes avaient pris au moins deux des trois medicaments suivants : la tolterodine, I'oxybutynine et I'imipramine. Elles ont alors subi un test de stimulation allant de trois a sept jours pendant lequel on a place deux electrodes temporaires dans I'orifice S3, une de chaque cote, reliees a un appareil portatif externe de stimulation. Pendant cette periode, chaque sujet a note, dans un carnet personnel, chaque miction, chaque incident d'incontinence, Ie nombre de serviettes hygieniques utilisees ainsi que les symptomes de besoin imperieux, de pollakiurie et de nocturie. Si on a constate, objectivement et subjectivement, une amelioration d'au moins 50 pour cent, on a offert aux sujets d'installer un implant permanent. Toutes les interventions ont ete faites en salle d'operation. On a place une electrode permanente d'un cote de I'orifice S3 apres avoir fait une petite incision verticale (de 5 a 7 cm) sur Ie sacrum. Le corps de I'electrode a ete glisse sous la peau et branche a un dispositif de stimulation implante dans la partie superieure de la fesse au moyen d'une seconde incision. Les sujets ont ete suivis, en moyenne, pendant 12,2 mois (de 7 a 16 mois).
AUGUST 2001
Resultats : L'age moyen des sujets etait de 55,1 ans (de 30 it 76 ans). Tous les sujets ont connu une baisse importante des mictions imperieuses, du besoin imperieux, de la pollakiurie et de la nocturie. Huit femmes n'ont maintenant plus d'incidents d'incontinence et ne portent plus de serviettes hygieniques ; les deux autres n'en utilisent qu'une par jour. Chacune de ces femmes utilisait au moins quatre serviettes par jour avant la pose de I'implant. Chacune d'elles decrit maintenant son besoin imperieux comme {( adequat ». La description du besoin imperieux avant I'intervention comprenait : {( modere » (2 sujets), {( constant» (un sujet) et {( fort» (sept sujets). La frequence est maintenant d'au moins deux heures chez chacune des femmes et, chez cinq d'entre elles, elle atteint quatre heures. Neuf d'entre elles urinaient toutes les heures avant I'implant et huit avaient trois episodes ou plus de nocturie. La plupart d'entre elles ne doivent maintenant uriner qu'une fois par nuit. II est aussi interessant de noter qu'une des participantes qui souffrait aussi d'incontinence anale a ete guerie a la suite de cette therapie. Une autre, qui avait de longs antecedents de constipation chronique et qui n'avait des selles qu'une fois par semaine en moyenne, a maintenant des selles quotidiennes. Chacune des dix femmes a indique sa satisfaction et a repondu {( oui » a la question de savoir si elle accepterait encore d'ihre traitee par cette technique. Aucun effet secondaire n'a ete constate. Conclusions: La stimulation des nerfs sacres est une nouvelle therapie prometteuse pour les femmes dont I'incontinence imperieuse ainsi que Ie besoin imperieux, la frequence et la nocturie qui y sont lies, sont refractaires. Cette technique semble a la fois securitaire et efficace. II faudra mener des etudes a long terme portant sur un plus grand nombre de sujets pour en definir Ie role definitif pour Ie traitement de la vessie hyperactive. II faudra aussi examiner Ie role possible de la stimulation des nerfs sac res chez les femmes souffrant de troubles intestinaux et de douleurs pelviennes.
J Obstet
Gynaecol 200 I;23(8):667-72
Sacral nerve stimulation is proposed as a new therapy for consideration by women with urge incontinence who have failed standard therapies. Its mechanism of action remains unclear. Sacral nerve stimulation is thought to involve modulation of various neural pathways, resulting in enhancement of inhibitory impulses to the detrusor muscle. 15,16 It may decrease spasticity of the pelvic floor by converting fast-twitch fibres to slow-twitch ones, or by interrupting chronically established pathologic reflex arcs. It may work in a manner similar to cardiac pacemakers by delivering constant or intermittent impulses, thereby overriding nervous control of the bladder. We report our initial experience with sacral nerve stimulation in women with intractable urge incontinence. MATERIALS AND METHODS ,
Women were recruited from the Continence Management Institute of St. Luke's Hospital, a urogynaecologic referral practice, between December 1998 and December 1999. To be eligible for sacral nerve stimulation therapy, the women had to have failed conservative therapy and at least two anticholinergic medication trials. All subjects had urge incontinence with varying degrees of urgency, frequency, and nocturia. Subjects underwent a complete history and physical examination, uroflowmetry, urinalysis, and a post-void residual determination by ultrasound. Subjects also kept a three day voiding diary prior to their initial visit. Women with neurological conditions, post-void residuals greater than 100 cc or who had demonstrable stress urinary incontinence with a comfortably full bladder were excluded. Test stimulation was done in the office under local anesthesia (Figure 1), and involved the placement of temporary electrodes into S3 foramen bilaterally, attached to a portable external FIGURE I
INTRODUCTION
TEST STIMULATION
Fifteen to 30 percent of women over the age of 65 in the United States are incontinent. l The annual cost to care for women with urinary incontinence is estimated at $11.2 billion (US D) in the community and $5.2 billion in nursing homes. l Urinary urge incontinence is particularly distressing for many women, as urine leakage is often unpredictable and can be of large volume. Women with urge incontinence often have additional symptoms of frequency, nocturia, and occasionally enuresis that can be debilitating and lead to social isolation. Standard treatment for urge incontinence includes behavioural therapy,2,3 dietary modification,4 pelvic muscle exercises,5 biofeedback,5,6 pelvic floor electrical stimulation,7,8 and the use of various medications. 9-11 While many women respond well to these therapies, 15 to 40 percent are either refractory or do not reach their goals of improvement. 12, 13 Previously, these women were left to either live with their symptoms or to consider a major surgical intervention such as augmentation cystoplasty. 12,14 JOGC
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stimulation device. Stimulation of the S3 nerve produces a characteristic levator ani contraction, which manifests as a "bellowing" of the vagina and rectum. The stimulated S3 nerve also causes flexion of the great toe. These signs, along with the patient's reporting of a sensation of pulling in the vagina and rectum, are used to confirm correct placement of the electrodes. Twenty-one women with intractable urge incontinence underwent a three to seven day test stimulation. 17,18 The range of duration for each test was based on when each woman would return to the office for subsequent follow-up, with no difference in test success based on its duration. Subjects completed a detailed voiding diary for three days immediately prior to and then throughout the test period. The diary contained information on episodes of incontinence and pad use, as weJJ as symptoms of urgency, frequency, and nocturia. Stimulation was always unilateral, but subjects were instructed to switch sides about halfWay through the test period and document on their diaries when they did so. The test stimulation was considered positive if the woman had at least a 50 percent improvement, both objectively and subjectively; in her symptoms. Those women who had positive test stimulations were then offered a permanent implant. Thirteen out of21 women (62%) had positive test stimulations, and 10 decided to have the implant. This procedure was done in the operating room under general anesthesia without neuromuscular blockade (Figure 2). A permanent electrode was placed in the S3 foramen on one side through a small (5-7 cm) vertical incision over the sacrum. The side that was found to be more effective during the test stimulation was usually chosen. Localization of the S3 nerve was accomplished in a manner similar to that described for the test stimulation. The electrode was secured to the sacrum with a bone anchor. The electrode body FIGURE 2 PERMANENT IMPLANT
was then tunneled underneath the skin and connected to the stimulating device implanted in the upper buttock through a second small (5-7 em) horizontal incision. The stimulating device was usuaJJy implanted on the woman's dominant side. Subjects remained in hospital overnight. They returned to the office one to two weeks post-operatively to have the device turned on and programmed. The subjects have been followed for an average of 12.2 months (range 7-16 months). To be eligible for sacral nerve stimulation, all subjects underwent weekly outpatient treatments of pelvic muscle reeducation, biofeedback, and pelvic floor electrical stimulation for six to 12 weeks. These 30 minute treatments were carried our in our office by trained nurses and included dietary modification, bladder retraining, and a bowel program if appropriate. All women who had previously demonstrated levator muscle weakness were able to isolate and improve pelvic floor elevation after this therapy. In addition, all women had trials of at least two of tolterodine, oxybutynin or imipramine. Medications were discontinued in all cases either because of a lack of efficacy or due to unwanted side effects, particularly dry mouth. RESULTS
The average duration of bladder symptoms was 6.8 years (range 2.1 to 20.0 years). One woman had a successfullaparoscopic Burch procedure at a different institution for stress urinary incontinence approximately one year prior to presentation. No other subjects had undergone previous incontinence surgery. Physical examinations were unremarkable except for weakness of the levator ani muscles in seven women initially, associated with an inability to significantly elevate the pelvic floor on demand. Interestingly, these women reported having done Kegel exercises in the past. None of the women had demonstrable stress incontinence or any significant pelvic organ prolapse. Uroflowmetry revealed decreased mean flow rates (less than 10 cclsec) in three women with straining patterns. All FIGURE) PAD USE . .. . ,'
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nl Ilmpl nl
women had post-void residual urine volumes less than 100 cc and negative urinalyses. The average age of the 10 women who chose the permanent implant was 55.1 years (range 30-76 years). All women were using at least four pads daily before the implant (Figure 3). The average follow-up for the implanted women was 12.2 months (range 7-16 months). Three women who had positive tests chose not to pursue the permanent implant. Two of these women had interstitial cystitis and opted for continued medical therapy and periodic bladder instillations. The other had chronic constipation, averaging one bowel movement per week. During the test period, she had daily bowel movements, bur did not want her bowel function to change. All 10 women had a marked improvement in their bladder symptoms as determined by their histories and voiding diaries. In all cases, the improvement with the permanent implant was at least as good or better than the results of the test stimulation. Eight women were completely continent after the implant and no longer used pads; the other two used only one pad per day. Prior to and after the surgical implantation, subjects were asked to describe their sensations of urgency from a list of several descriptive words (Table 1). All now label their urgency as "appropriate." Preimplant descriptions included "moderate," "constant," and "strong" in two, one, and seven women respectively. All women subjectively reported that they are now able to postpone voiding, whereas eight were unable to do this prior to the implant. Nine patients voided at least every hour prior to the implant. On post-implant assessment, all were able to hold at least two hours, and five women were able to hold four hours between voiding episodes (Figure 4). The mean number of voids per 24 hours decreased from 16.2 (range 6-25) to 8.4 (range 5-12) (p < 0.001). Nocturia was also reduced by the implant. Prior to surgery, eight women had at least three episodes of nocturia before surgery. After surgery, three women awakened twice per night on average to void post-implant; the rest got up either once or not at all (Figure 5). Several other clinical observations were noted. One woman who complained of fecal incontinence pre-operatively was cured by the implant. Another woman with a history of
r GURE .. URINARY FREQUENCY
o
chronic constipation and an average of one bowel movement per week now moves her bowels daily. Three out of the 10 women had cystoscopically diagnosed interstitial cystitis, and all three have achieved substantial improvement in their symptoms. One of these women turned the unit off for several days to undergo an unrelated surgical procedure, approximately one year after she had received the implant. Her irritative bladder symptoms returned almost immediately, and were then corrected again after the device was turned back on. There were no major complications during this study. All subjects were discharged on the first post-operative day withour incident. At time of writing, all women were still using the implant, although one woman is considering having it removed because of discomfort over the generator site when she sits. Her symptoms remain well controlled, however. There has not been any reduction in bladder control over time, and all subjects continue to be followed every three to six months.
FIGURE S NOCTURIA
e
TABLE I
URINARY URGENCY: DESCRIPTIVE WORDS • None • Appropriate • Mild • Moderate • Strong • Constant
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DISCUSSION
Urinary urge incontinence remains a challenging problem for both patients and clinicians. Standard behavioural and pharmacological therapies fail to provide adequate symptom control in 15 to 40 percent of women suffering from urge incontinence. l2 •l3 Among those women in whom standard treatments had failed, sacral nerve stimulation produced excellent therapeutic results. The pathophysiology of urge incontinence and overactive bladder is poorly understood, but may involve sacral neuropathy. 15.16 It is thus not surprising that a therapy targeting sacral nerves rather than the bladder might provide a dramatic improvement in symptoms. There do not seem to be any parameters in a patient's history, physical examination or investigations that predict positivity of the sacral nerve stimulation test procedure: 50 to 60 percent of women with urge incontinence will test positive.14.19-21 Patients either experience a dramatic reduction in urge incontinence, pad use, nocturia, and voids per day, or virtually no change at all. It is possible that poor lead placement or lead migration during the test may in part explain why some patients have little to no improvement. 20.21 As our understanding of how sacral nerve stimulation works in this setting is theoretical, it is not surprising that some women with overactive bladder symptoms and urge incontinence would be refractory to this therapy. As a routine, we did not carry out multichannel urodynamic testing in our patients prior to test stimulation or the surgical implant procedure. There are several reasons for this. First, the presence or absence of detrusor instability has no bearing on the management of a woman with purely overactive bladder symptoms.22,23 Such a woman is a candidate for conservative treatment or pharmacological therapy based on her hisrory, physical examination, voiding diary, normal uroflowmetry, normal post-void residual measurement, and negative urinalysis. Second, demonstrable detrusor instability on urodynamic testing is of no help in predicting success or failure with sacral nerve stimulation therapy.19 To our knowledge, the only reliable pre-operative indicator of sacral nerve stimulation efficacy is a positive test stimulation. While we do not discount the value of extensive testing in some women with overactive bladders, the results of any further work-up or urodynamic testing were unlikely to have influenced their management. We do acknowledge that pre- and post-implant urodynamics could have been useful in elucidating how sacral nerve stimulation affects various bladder parameters. We did not routinely offer cystoscopy as part of our evaluation unless the woman had hemaruria on urinalysis, in the absence of infection. Five women in our series, however, did undergo cystoscopic evaluation. Three women with interstitial cystitis were successfully treated by sacral nerve stimulation, suggesting sacral nerve stimulation to be an important treatment option for women with this chronic and often debilitating condition. Two other JOGC
women had normal cystoscopies. Since a prerequisite for sacral nerve stimulation is urge incontinence refractory to standard treatment, many such women will be suspicious for interstitial cystitis and will undergo cyStoscopy. This is particularly true in younger women with a longstanding history of irritative bladder symptoms. These women may wish to try other therapies, such as pentosan polysulfate (Elmiron®) or bladder instillations, prior to considering sacral nerve stimulation. It is reasonable, however, to proceed directly to a test stimulation in such patients, since confirming the diagnosis of interstitial cystitis is not predictive of success or failure with this therapy. If the woman has a positive test, our experience suggests a permanent implant will dramatically improve her bladder symptoms regardless of the findings at cystoscopy. While it is possible that certain conditions, such as bladder tumours, stones, and sutures from prior surgeries may have been missed by not performing cystoscopy routinely, we feel that this is highly unlikely. Such patients would not be expected to benefit from sacral nerve stimulation, since the pathophysiology is unrelated to their sacral nervous system. We question the likelihood of discovering these anatomical findings in the face of a normal urinalysis. The unexpected finding in our study of improved bowel function in two women, one with fecal incontinence and the other with chronic constipation, raises interesting questions regarding other potential indications for sacral nerve stimulation. It is possible that the pathophysiology of chronic bowel dysfunction, like that of urge incontinence, may be a result of worsening sacral neuropathy. It is biologically plausible that the sacral nervous system of a woman with chronic constipation might stimulate the distal colon and rectum. Many women with urge incontinence and overactive bladder also suffer from poor bowel motility and incomplete fecal evacuation. Similarly, fecal incontinence, in the face of an anatomically normal anal sphincter, may be explained by abnormal sacral nerve impulses or aberrant reflex pathways to the rectum and anus. It would be reasonable to suggest that modulation of these impulses may therefore improve both bladder and bowel function. This finding requires further study. We have not seen the same rate oflead migration with the permanent implant that has been reported by other groups,20.21 and did not have to reoperate on any of the women in our study. It is possible that our approach of securing the electrode to the sacrum with a bone anchor may reduce the incidence of migration. Further, in our study, intraoperative fluoroscopy was used in addition to anatomical landmarks and characteristic motor responses, to confirm lead placement. This study is limited by the small number of subjects, the lack of a control group, and the unblinded nature of the intervention for both the subjects and the investigators. Blinding the subjects would be difficult to achieve, as we believe it unethical to carry out a sham surgical procedure. It is, however, an encouraging initial experience with a new therapy that has potential AUGUST 2001
application to several pelvic floor disorders. Further study is warranted to investigate the role of sacral nerve stimulation therapy in the treatment of refractory urge incontinence. CONCLUSION
Sacral nerve stimulation is a promising new therapy for women with intractable urge incontinence and associated urgency, frequency, and nocturia. It appears to be both safe and efficacious. Long term studies with larger numbers of subjects will determine its ultimate place in the management of the overactive bladder. The potential role of sacral nerve stimulation in women with bowel dysfunction and pelvic pain also needs to be investigated. REFERENCES I.
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United States Department of Health and Human Services. Urinary Incontinence in Adults:Acute and Chronic Management. Public Health Service.Agency for Health Care Policy and Research:AHCPR Publication No. 96-0682. March 1996. Fantl )A.Wyman)F. McClish OK. Harkins Sw. Elswick RK.Taylor JR. et al. Efficacy of bladder training in older women with urinary incontinence. JAm Med Assoc 1991 ;265:609-13. Jarvis GJ. and Millar DR. Controlled trial of bladder drill for detrusor instability. Br Med J 1980;281 :322-33. Weinberger MW. Goodman BM. Carnes M. Long-term efficacy of nonsurgical urinary incontinence treatment in elderly women.J Gerontol A Bioi Sci Med Sci I999;54(3):M 117-21. Wyman JF. Fantl JA. McClish OK. Bump RC. Comparative efficacy of behavioral interventions in the management of female urinary incontinence. Continence Program for Women Research Group.Am J Obstet Gynecol 1998; 179(4):999-1 007. Burgio KL. Locher JL. Goode PS. Hardin JM. McDowell BJ. Dombrowski M. et al. Behavioral vs. drug treatment for urge urinary incontinence in older women: a randomized controlled trial. JAm Med Assoc 1998;280(23): 1995-2000. Brubaker L. Benson JT. Bent A, ClarkA, Shott S.Transvaginal electrical stimulation for female urinary incontinence.Am J Obstet Gynecol 1997; 177(3):536-40. Caputo RM. Benson JT. McClellan E. Intravaginal maximal electrical stimulation in the treatment of urinary incontinence.J Repro Med 1993;38(9):667-71. Abrams P, Freeman R.Anderstrom C. Mattiasson A. Tolterodine. a new anti muscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Br J Urol 1998;81 (6): 80 I-I O. Goldenberg MM.An extended-release formulation of oxybutynin chloride for the treatment of overactive urinary bladder. Clin Ther 1999;21 (4): 634-42. Appell RA. Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis. Urol I997;50(Suppl GA):90-6. Clinical Practice Guideline: Urinary Incontinence in Adults. Rockville. Maryland: US Department of Health and Human Services. 1992; pp.38-43. National Association for Continence (NAFC). Consumer Focus '96: A Survey of Community Dwelling Incontinent People. 1996. Bosch JL. Groen J. Sacral (S3) segmental nerve stimulation as a treatment for urge incontinence with detrusor instability: results of chronic electrical stimulation using an implantable neural prosthesis. J Urol 1995; 154:504-7. Thon WF. Baskin LS.Jonas U. Tanagho EA, Schmidt RA. Neuromodulation of voiding dysfunction and pelViC pain. World J Urol 1991 ;9: 138-41.
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16. Bosch R. Groen J. Effects of sacral segmental nerve stimulation on urethral resistance and bladder contractility: how does neuromodulation work in urge incontinence patients! Neurourol Urodynam 1995; 14: 502. 17. Schmidt RA. Senn E.Tanagho EA. Functional evaluation of sacral nerve root integrity: report of a technique. Urol 1990;35:388-92. 18. Siegel SW Management of voiding dysfunction with an implantable neuroprosthesis. Urol Clin N Am 1992; 19: 163-70. 19. Koldewijn EL. Rosier PF. Meuleman EJ. Koster AM. Debruyne FM. van Kerrebroeck PE. Predictors of success with neuromodulation in lower urinary tract dysfunction: results of trial stimulation in 100 patients. J Urol 1994; 152: 2071-5. 20. Janknegt RA.Weil EH. Eerdmans PH. Improving neuromodulation technique for refractory voiding dysfunctions: two-stage implant. Urol 1997;49:358-62. 21. Schmidt RA.Jonas U. Oleson KA.Janknegt RA. Hassouna MM. Siegel Sw. et al. Sacral nerve stimulation for the treatment of refractory urinary urge incontinence.) Urol 1999;162:352-7. 22. Karram MM. Partoll L. Rahe J. Efficacy of nonsurgical therapy for urinary incontinence.J Repro Med 1996;41 (4):215-9. 23. Wyman JF. Fantl JA. McClish OK. Harkins Sw. Uebersax JS. Ory MG. Quality of life following bladder training in older women with urinary incontinence.lnt Urogynecol J Pelvic Floor Dysfn 1997;8(4):223-9.
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