- Email: [email protected]
Sacral Neuromodulation with an Implantable Pulse Generator in Children with Lower Urinary Tract Symptoms: 15-Year Experience
Sacral Neuromodulation with an Implantable Pulse Generator in Children with Lower Urinary Tract Symptoms: 15-Year Experience Luitzen-Albert Groen,* Piet Hoebeke, Nele Loret, Charles Van Praet, Erik Van Laecke, Raes Ann, Johan Vande Walle and Karel Everaert From the Pediatric Urologic Nephrologic Center, Ghent University Hospital, Ghent, Belgium
Purpose: Sacral nerve modulation with an implantable pulse generator is not an established treatment in children. This therapy has been described for dysfunctional elimination syndrome and neurogenic bladder. We report 2 new indications for this approach in children, ie bladder overactivity and Fowler syndrome. The aim of this study was to improve the results of future treatment for sacral neuromodulation in children by describing factors favorable for good outcomes with this method. Materials and Methods: A total of 18 children 9 to 17 years old were studied. Mean ⫾ SD followup was 28.8 ⫾ 43.8 months. Of the patients 16 underwent S3 sacral neuromodulation and 7 underwent pudendal stimulation (5 as a revision, 2 from the beginning). Results: Initial full response was achieved in 9 of 18 patients (50%) and partial response in 5 (28%). In patients presenting with incontinence mean ⫾ SD number of incontinence episodes weekly improved significantly from 23.2 ⫾ 12.4 to 1.3 ⫾ 2.63 (p ⬍0.05). In patients requiring clean intermittent catheterization there was a significant decrease in mean ⫾ SD daily frequency of catheterization from 5.2 ⫾ 1.6 to 2.0 ⫾ 1.9 (p ⬍0.05). At the end of the study 6 of 15 patients (40%) had a full response and 5 (33%) had a partial response, while 4 implantable pulse generator devices (27%) were explanted because of failure. Conclusions: Sacral neuromodulation is feasible in the pediatric population, with good short-term (78% full or partial response) and satisfactory long-term results (73%). Sacral neuromodulation can offer good results for overactive bladder, dysfunctional elimination syndrome and Fowler syndrome. Pudendal nerve stimulation is a feasible salvage treatment that can be useful in cases when S3 implantation is impossible or unsuccessful.
Abbreviations and Acronyms CIC ⫽ clean intermittent catheterization DES ⫽ dysfunctional elimination syndrome IPG ⫽ implantable pulse generator MMC ⫽ meningomyelocele OAB ⫽ overactive bladder PNE ⫽ percutaneous nerve evaluation SNM ⫽ sacral nerve modulation UTI ⫽ urinary tract infection Submitted for publication November 30, 2011. Study received institutional review board approval (BE670201110913). *E-mail: [email protected].
See Editorial on page 1076.
Key Words: implantable neurostimulators; pediatrics; urinary bladder, neurogenic; urinary bladder, overactive; urination disorders SACRAL nerve modulation with an implantable pulse generator was approved by the Food and Drug Administration for use in adults in 1997. However, as evidenced by the lack of publications regarding its use in patients younger than 18 years,1 this method is not an established treat-
ment in children. This approach has previously been described for treating dysfunctional elimination syndrome and neurogenic bladder dysfunction.2– 6 We studied the use of sacral nerve modulation to treat for dysfunctional elimination syndrome and neurogenic bladder, as well as for 2 not previ-
0022-5347/12/1884-1313/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
http://dx.doi.org/10.1016/j.juro.2012.06.039 Vol. 188, 1313-1318, October 2012 RESEARCH, INC. Printed in U.S.A.
AND
www.jurology.com
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SACRAL NEUROMODULATION IN CHILDREN WITH URINARY SYMPTOMS
ously described indications in children, namely bladder overactivity and Fowler syndrome. At our referral center for pediatric urology and nephrology, which treats a large population of children with lower urinary tract symptoms, neuromodulation was used as a last treatment option for 18 patients with severe therapy resistant conditions. The aim of this study was to improve the results of future SNM treatment in children by detecting patient characteristics favorable for good outcomes with this treatment.
MATERIALS AND METHODS Three boys and 15 girls with a mean age of 15 years (range 9 to 17) who were consecutively treated with sacral neuromodulation between 1996 and 2011 made up the population of this retrospective study. Individuals chosen to undergo SNM were selected on a case-by-case basis. In all patients videourodynamic evaluation was performed preoperatively. Indications for neuromodulation were OAB, DES, Fowler syndrome and neurogenic bladder. These evaluations were done after approval of the institutional review board (BE670201110913), and after obtaining patient and parental informed consent. A total of 13 patients with nonneurogenic symptoms completed an in-house protocol consisting of outpatient urotherapy/medical therapy and subsequently 2 weeks of in-hospital training by a pediatric urotherapist, with screening and support offered by a child psychologist. At the end of the protocol symptoms persisted in 24% of the patients.7 Only some of these patients were eligible for SNM. Urotherapy consisted of concomitant or subsequent combinations of multiple treatment modalities, including cognitive bladder training, capacity increasing exercises, daytime alarm, biofeedback training, percutaneous nerve stimulation and transcutaneous nerve stimulation tailored to the specific needs of individual patients.8,9 In patients with low bladder capacity or urgency anticholinergic drugs were added when OAB was suspected. Of the patients 10 were treated with off-label use of solifenacin or duloxetine and 2 received intravesical injections of botulinum toxin A. If Fowler syndrome was suspected, qualitative needle electromyography was performed to confirm the diagnosis. A test phase was performed by placing a PNE wire or tined lead percutaneously in the S3 foramen. The PNE wire is connected directly to the external pulse generator, and the tined lead is connected via an intermediary connection cable that is tunneled to the opposite side to prevent infection of the tined lead. The tined lead is connected in a second stage directly to the IPG in case of good results during the test phase (fig. 1). Criteria for IPG placement were 50% reduction of incontinence episodes, 50% decrease in post-void residual volume, 50% reduction of necessity for CIC and 50% improvement in urinary frequency. Implantation rate after a positive test was 83% (15 of 18 cases). The procedure was performed by an experienced functional urologist accord-
Figure 1. Flow chart of test phase and implantation
ing to the technique of Spinelli et al,10 –12 with the IPG implanted in the buttock position.13 Seven patients underwent pudendal nerve stimulation (fig. 2). Two patients underwent a successful pudendal 2-stage implant from the beginning, 1 because PNE could not achieve S3 stimulation and 1 because of a sacral lipoma. On revision 5 cases were converted to pudendal stimulation following dislocation (2) or unsuccessful S3 neuromodulation (3). Daytime incontinence was evaluated based on number of incontinence episodes, with quantity of urine loss measured as grams per day on 24-hour pad test. Voided volumes were documented in voiding diaries, with post-void residual measured by ultrasound or by post-void CIC volume in patients on CIC. Outcome was defined as 1) full response, ie 100% patient satisfaction and greater than 90% objective improvement for at least 1 implantation criterion; 2) partial response, ie patient satisfaction and 50% to 90% objective improvement for at least 1 implantation criterion, and 3) failure, ie less than 50% objective improvement or no patient satisfaction. Mean ⫾ SD followup was 28.8 ⫾ 43.8 months (median 11, range 0.5 to 180). Statistical analysis was done using the Wilcoxon signed rank test. Results are presented as means and standard deviation.
RESULTS SNM offered improvement in daytime continence (decreased number of incontinence episodes and quantity of urine loss measured as grams per day on 24-hour pad test), urgency, enuresis, encopresis and/or need for CIC (fig. 3). A full response was achieved in 9 of 18 patients (50%) and a partial response in 5 (28%). In patients presenting with incontinence mean ⫾ SD weekly episodes improved
SACRAL NEUROMODULATION IN CHILDREN WITH URINARY SYMPTOMS
Figure 2. Flow chart of sacral/pudendal neuromodulation
from 23.2 ⫾ 12.4 to 1.3 ⫾ 2.63 (Wilcoxon test, p ⬍0.05). Mean ⫾ SD incontinence volume decreased from 227 ⫾ 139.1 gm to 3.1 ⫾ 3.1 gm (Wilcoxon test, p not significant). In patients presenting with urgency or
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residual volume, improvement was not statistically significant due to low patient numbers. In patients requiring CIC mean daily frequency of catheterization decreased from 5.2 ⫾ 1.6 to 2.0 ⫾ 1.9 (Wilcoxon test, p ⬍0.05). In 2 patients presenting with encopresis and in 1 presenting with enuresis as associated complaints these conditions resolved with IPG (fig. 3). Complications were observed in 10 patients, with infection noted in 2, dislocation/loss of effect in 6 and pain at the implantation site in 2. Eight patients underwent reoperation for complications, consisting of infection in 2 and dislocation/ loss of effect in 6. Two patients required reintervention because of battery depletion, which should not be considered a complication, but rather a sign of success (long-term use of the battery). At the end of the study 6 of 15 patients (40%) had a full response and 5 (33%) had a partial response, while the IPG devices were explanted because of failure in 4 (27%). As mentioned previously, patients underwent sacral nerve modulation for 4 different indications, ie OAB, DES, Fowler syndrome and neurogenic bladder. Three of 4 patients in the OAB group suffered from severe incontinence. These patients pre-
Figure 3. Symptoms present before treatment with external (test) and internal (implantable) pulse generator. LUTS, lower urinary tract symptoms.
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SACRAL NEUROMODULATION IN CHILDREN WITH URINARY SYMPTOMS
sented with mean ⫾ SD daily incontinence episodes of 4.3 ⫾ 1.53 with a mean ⫾ SD total daily volume of 142 ⫾ 51.6 gm. Mean ⫾ SD daily incontinence episodes were improved to 2.4 ⫾ 1.25 and volume to 4.8 ⫾ 2.84 gm with the test stimulator. After definitive IPG implantation 2 of 3 patients had a full response regarding incontinence, and enuresis resolved in 1. Urgency symptoms resolved in 3 of 4 patients. In this group all 4 patients had suffered from recurrent UTIs before IPG, and none had recurrence after IPG. In the 2 patients with DES mean ⫾ SD daily voiding frequency improved from 8 ⫾ 1 to 6.2 ⫾ 0.21. Post-void residual volume decreased from 360 to 30 ml in 1 patient, resulting in a dramatic decrease in the number of UTIs. In the remaining patient postvoid residual volume decreased less dramatically, although pelvic pain and dysuria resolved. In the 7 patients with Fowler syndrome incontinence and need for CIC were the main criteria for implantation. Three patients had a full response to SNM for incontinence, 2 had a partial response and 2 did not meet implantation criteria. Urinary retention requiring daily CIC was present in 3 subjects, of whom 1 achieved cure and could stop CIC entirely. Of the 5 patients with neurogenic bladder 3 suffered from urinary incontinence, 2 from enuresis, 2 from encopresis and 4 from recurrent UTIs. In all 3 patients with MMC the IPG was removed because of disappointing results. The patient with anal atresia had a full response, with greater than 90% decrease
in incontinence episodes, and the patient with Guillain-Barre syndrome had less urgency, incontinence and enuresis (see table).
DISCUSSION In a highly selected patient population suffering with extreme therapy resistant lower urinary tract conditions we could achieve a full response in 50% (9 of 18 patients) and a partial response in 28% (5) using SNM. This outcome can be considered an encouraging result for a patient population with no remaining treatment options. The success rate might increase with more selective use of SNM for specific indications. Subgroup analysis was performed to detect patient characteristics/indications favorable for good outcomes. Results for overactive bladder, dysfunctional elimination syndrome, Fowler syndrome and neurogenic bladder were compared. A positive experience for overactive bladder, Fowler syndrome and DES was observed. The results for DES confirm the findings of Humphreys et al,2 who observed 16% resolution and 68% improvement of incontinence. The series of Roth at al demonstrated a higher success rate, with complete resolution of incontinence in 75% of cases.3 The experience with MMC as a cause of neurogenic bladder was disappointing in our study and confirmed the results of Guys et al, who found no statistical difference in a prospective study comparing IPG implantation in 21 patients
Patient data Implantation Criteria
Pt No.
Diagnosis
1 2
MMC Guillain-Barre syndrome
Not met Urgency
3
OAB
Incontinence
4 5 6 7
MMC Anal atresia Fowler syndrome Fowler syndrome
Incontinence Incontinence Not met Need for CIC
8
Fowler syndrome
Incontinence
Fowler Fowler Fowler MMC DES DES Fowler OAB OAB OAB
Not met Incontinence Incontinence Incontinence Residual vol Residual vol Incontinence Incontinence Incontinence Frequency
9 10 11 12 13 14 15 16 17 18
syndrome syndrome syndrome
syndrome
Neuromodulation Type Pudendal nerve stimulation S3, revision to pudendal nerve stimulation Pudendal nerve stimulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation, revision to S3 sacral neuromodulation contralateral unsuccessful, revision to pudendal nerve stimulation successful Revision to pudendal nerve stimulation unsuccessful S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation Revision to pudendal nerve stimulation Revision to pudendal nerve stimulation Revision S3 sacral neuromodulation
Results Failure Partial response Full response, infection/explantation, new pudendal nerve stimulation implant contralateral Failure Full response, long-term full response Failure Full response, long-term response
Partial response, failure after revision Failure Full response, no revisions Partial response Partial response, infection, failure after new implant Partial response Full response Full response, long-term failure Full response, full response after revision Full response, initial full response after revision, long-term failure Full response, persistent enuresis
SACRAL NEUROMODULATION IN CHILDREN WITH URINARY SYMPTOMS
with MMC and controls.5 Similar results were observed in adults with neurogenic bladder in the series by Hohenfellner et al, who described 27 test stimulations and 11 IPG implantations.14 Unfortunately the reoperation rate in our series was high, mainly because of lead dislocation and infection. The high dislocation rate (6 of 15 cases) was cumbersome and probably the result of growth and more active movement in children compared to adults. Efforts should be made to improve the tined lead and adapt it for use in children. The infection rate was 13% (2 of 15 patients) and could be explained in 1 patient by the extended test period and 2-stage procedure. However, the test interval was not significantly longer in patients with an infection (Mann-Whitney test, p ⫽ 0.2). Nevertheless, efforts should be made to keep the interval as short as possible to prevent infection of the implant.
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The limitations of this study were the heterogeneity of population and the retrospective character, with less standardized followup compared to a prospective study. Therefore, a prospective study is actually planned based on the encouraging results of this retrospective series.
CONCLUSIONS Sacral neuromodulation is feasible in a pediatric population, with good short-term (78% full or partial response) and satisfactory long-term results (73%). Overactive bladder, DES and Fowler syndrome are promising indications. Neurogenic bladder caused by MMC is probably a less promising indication. Pudendal nerve stimulation is a feasible salvage solution and can be useful in cases when S3 implantation is impossible or unsuccessful.
REFERENCES 1. De Gennaro M, Capitanucci ML, Mosiello G et al: Current state of nerve stimulation technique for lower urinary tract dysfunction in children. J Urol 2011; 185: 1571.
6. Haddad M, Besson R, Aubert D et al: Sacral neuromodulation in children with urinary and fecal incontinence: a multicenter, open label, randomized, crossover study. J Urol 2010; 184: 696.
2. Humphreys MR, Vandersteen DR, Slezak JM et al: Preliminary results of sacral neuromodulation in 23 children. J Urol 2006; 176: 2227.
7. Hoebeke PB, Renson C, De Schryver M et al: Prospective evaluation of clinical voiding reeducation or voiding school for lower urinary tract conditions in children. J Urol 2011; 186: 648.
3. Roth TJ, Vandersteen DR, Hollatz P et al: Sacral neuromodulation for the dysfunctional elimination syndrome: a single center experience with 20 children. J Urol 2008; 180: 306. 4. McGee SM, Routh JC, Granberg CF et al: Sacral neuromodulation in children with dysfunctional elimination syndrome: description of incisionless first stage and second stage without fluoroscopy. Urology 2009; 73: 641. 5. Guys JM, Haddad M, Planche D et al: Sacral neuromodulation for neurogenic bladder dysfunction in children. J Urol 2004; 172: 1673.
8. Hoebeke PB, Renson C, Petillon L et al: Percutaneous electrical nerve stimulation in children with therapy resistant nonneuropathic bladder sphincter dysfunction: a pilot study. J Urol 2002; 168: 2605. 9. Hoebeke PB, Van Laecke E, Everaert K et al: Transcutaneous neuromodulation for the urge syndrome in children: a pilot study. J Urol 2001; 166: 2416. 10. Spinelli M, Giardiello G, Arduini A et al: New percutaneous technique of sacral nerve stimula-
tion has high initial success rate: preliminary results. Eur Urol 2003; 43: 70. 11. Spinelli M, Giardiello G, Gerber M et al: New sacral neuromodulation lead for percutaneous implantation using local anesthesia: description and first experience. J Urol 2003; 170: 1905. 12. Spinelli M, Malaguti S, Giardiello G et al: A new minimally invasive procedure for pudendal nerve stimulation to treat neurogenic bladder: description of the method and preliminary data. Neurourol Urodyn 2005; 24: 305. 13. Scheepens WA, Weil EH, van Koeveringe GA et al: Buttock placement of the implantable pulse generator: a new implantation technique for sacral neuromodulation—a multicenter study. Eur Urol 2001; 40: 434. 14. Hohenfellner M, Humke J, Hampel C et al: Chronic sacral neuromodulation for treatment of neurogenic bladder dysfunction: long-term results with unilateral implants. Urology 2001; 58: 887.
EDITORIAL COMMENT This interesting study adds to the literature evaluating IPG for functional lower urinary tract disorders. The main strength of the study and what differentiates it from others is that the authors categorized the lower urinary tract dysfunction into groups, enabling us to understand how IPG works in different situations. They confirmed that IPG may work for patients with underactive bladder and that it may be used in patients with refractory OAB. Also, they found that IPG failed in 3 patients with MMC. However, despite my belief that the neurogenic cases are unsuitable for this kind of treatment, the small numbers do not allow for any
definitive conclusions to be drawn regarding the level of effectiveness of IPG in these cases. Patients with incomplete neural disease might have a better outcome. The authors showed that at the end of the study 11 of 15 patients had a full or partial response, giving a 73% success rate. However, for the intentto-treat analysis the 3 patients who did not pass through the test phase should also be included for the calculation of the final outcome. When these individuals are included, the success rate decreases to 61%, which is still a good outcome for these difficult cases.
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SACRAL NEUROMODULATION IN CHILDREN WITH URINARY SYMPTOMS
The complication rate was in accordance with that reported in the literature, at around 25%.1 It would be interesting in the future to know the recurrence rate after device deactivation. The rate reported by Roth et al was 60% (3 of 5 cases, reference 3 in article). Finally, I encourage the authors to pursue their research, and I look for-
ward to future updates with more patients and longer follow-up. Ubirajara Barroso, Jr. Federal University of Bahia Bahiana School of Medicine and Public Health Salvador, Brazil
REFERENCE 1. Barroso U Jr, Tourinho R, Lordêlo P et al: Electrical stimulation for lower urinary tract dysfunction: a systematic review of the literature. Neurourol Urodyn 2011; 30: 1429.
Purpose: Sacral nerve modulation with an implantable pulse generator is not an established treatment in children. This therapy has been described for dysfunctional elimination syndrome and neurogenic bladder. We report 2 new indications for this approach in children, ie bladder overactivity and Fowler syndrome. The aim of this study was to improve the results of future treatment for sacral neuromodulation in children by describing factors favorable for good outcomes with this method. Materials and Methods: A total of 18 children 9 to 17 years old were studied. Mean ⫾ SD followup was 28.8 ⫾ 43.8 months. Of the patients 16 underwent S3 sacral neuromodulation and 7 underwent pudendal stimulation (5 as a revision, 2 from the beginning). Results: Initial full response was achieved in 9 of 18 patients (50%) and partial response in 5 (28%). In patients presenting with incontinence mean ⫾ SD number of incontinence episodes weekly improved significantly from 23.2 ⫾ 12.4 to 1.3 ⫾ 2.63 (p ⬍0.05). In patients requiring clean intermittent catheterization there was a significant decrease in mean ⫾ SD daily frequency of catheterization from 5.2 ⫾ 1.6 to 2.0 ⫾ 1.9 (p ⬍0.05). At the end of the study 6 of 15 patients (40%) had a full response and 5 (33%) had a partial response, while 4 implantable pulse generator devices (27%) were explanted because of failure. Conclusions: Sacral neuromodulation is feasible in the pediatric population, with good short-term (78% full or partial response) and satisfactory long-term results (73%). Sacral neuromodulation can offer good results for overactive bladder, dysfunctional elimination syndrome and Fowler syndrome. Pudendal nerve stimulation is a feasible salvage treatment that can be useful in cases when S3 implantation is impossible or unsuccessful.
Abbreviations and Acronyms CIC ⫽ clean intermittent catheterization DES ⫽ dysfunctional elimination syndrome IPG ⫽ implantable pulse generator MMC ⫽ meningomyelocele OAB ⫽ overactive bladder PNE ⫽ percutaneous nerve evaluation SNM ⫽ sacral nerve modulation UTI ⫽ urinary tract infection Submitted for publication November 30, 2011. Study received institutional review board approval (BE670201110913). *E-mail: [email protected].
See Editorial on page 1076.
Key Words: implantable neurostimulators; pediatrics; urinary bladder, neurogenic; urinary bladder, overactive; urination disorders SACRAL nerve modulation with an implantable pulse generator was approved by the Food and Drug Administration for use in adults in 1997. However, as evidenced by the lack of publications regarding its use in patients younger than 18 years,1 this method is not an established treat-
ment in children. This approach has previously been described for treating dysfunctional elimination syndrome and neurogenic bladder dysfunction.2– 6 We studied the use of sacral nerve modulation to treat for dysfunctional elimination syndrome and neurogenic bladder, as well as for 2 not previ-
0022-5347/12/1884-1313/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
http://dx.doi.org/10.1016/j.juro.2012.06.039 Vol. 188, 1313-1318, October 2012 RESEARCH, INC. Printed in U.S.A.
AND
www.jurology.com
1313
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SACRAL NEUROMODULATION IN CHILDREN WITH URINARY SYMPTOMS
ously described indications in children, namely bladder overactivity and Fowler syndrome. At our referral center for pediatric urology and nephrology, which treats a large population of children with lower urinary tract symptoms, neuromodulation was used as a last treatment option for 18 patients with severe therapy resistant conditions. The aim of this study was to improve the results of future SNM treatment in children by detecting patient characteristics favorable for good outcomes with this treatment.
MATERIALS AND METHODS Three boys and 15 girls with a mean age of 15 years (range 9 to 17) who were consecutively treated with sacral neuromodulation between 1996 and 2011 made up the population of this retrospective study. Individuals chosen to undergo SNM were selected on a case-by-case basis. In all patients videourodynamic evaluation was performed preoperatively. Indications for neuromodulation were OAB, DES, Fowler syndrome and neurogenic bladder. These evaluations were done after approval of the institutional review board (BE670201110913), and after obtaining patient and parental informed consent. A total of 13 patients with nonneurogenic symptoms completed an in-house protocol consisting of outpatient urotherapy/medical therapy and subsequently 2 weeks of in-hospital training by a pediatric urotherapist, with screening and support offered by a child psychologist. At the end of the protocol symptoms persisted in 24% of the patients.7 Only some of these patients were eligible for SNM. Urotherapy consisted of concomitant or subsequent combinations of multiple treatment modalities, including cognitive bladder training, capacity increasing exercises, daytime alarm, biofeedback training, percutaneous nerve stimulation and transcutaneous nerve stimulation tailored to the specific needs of individual patients.8,9 In patients with low bladder capacity or urgency anticholinergic drugs were added when OAB was suspected. Of the patients 10 were treated with off-label use of solifenacin or duloxetine and 2 received intravesical injections of botulinum toxin A. If Fowler syndrome was suspected, qualitative needle electromyography was performed to confirm the diagnosis. A test phase was performed by placing a PNE wire or tined lead percutaneously in the S3 foramen. The PNE wire is connected directly to the external pulse generator, and the tined lead is connected via an intermediary connection cable that is tunneled to the opposite side to prevent infection of the tined lead. The tined lead is connected in a second stage directly to the IPG in case of good results during the test phase (fig. 1). Criteria for IPG placement were 50% reduction of incontinence episodes, 50% decrease in post-void residual volume, 50% reduction of necessity for CIC and 50% improvement in urinary frequency. Implantation rate after a positive test was 83% (15 of 18 cases). The procedure was performed by an experienced functional urologist accord-
Figure 1. Flow chart of test phase and implantation
ing to the technique of Spinelli et al,10 –12 with the IPG implanted in the buttock position.13 Seven patients underwent pudendal nerve stimulation (fig. 2). Two patients underwent a successful pudendal 2-stage implant from the beginning, 1 because PNE could not achieve S3 stimulation and 1 because of a sacral lipoma. On revision 5 cases were converted to pudendal stimulation following dislocation (2) or unsuccessful S3 neuromodulation (3). Daytime incontinence was evaluated based on number of incontinence episodes, with quantity of urine loss measured as grams per day on 24-hour pad test. Voided volumes were documented in voiding diaries, with post-void residual measured by ultrasound or by post-void CIC volume in patients on CIC. Outcome was defined as 1) full response, ie 100% patient satisfaction and greater than 90% objective improvement for at least 1 implantation criterion; 2) partial response, ie patient satisfaction and 50% to 90% objective improvement for at least 1 implantation criterion, and 3) failure, ie less than 50% objective improvement or no patient satisfaction. Mean ⫾ SD followup was 28.8 ⫾ 43.8 months (median 11, range 0.5 to 180). Statistical analysis was done using the Wilcoxon signed rank test. Results are presented as means and standard deviation.
RESULTS SNM offered improvement in daytime continence (decreased number of incontinence episodes and quantity of urine loss measured as grams per day on 24-hour pad test), urgency, enuresis, encopresis and/or need for CIC (fig. 3). A full response was achieved in 9 of 18 patients (50%) and a partial response in 5 (28%). In patients presenting with incontinence mean ⫾ SD weekly episodes improved
SACRAL NEUROMODULATION IN CHILDREN WITH URINARY SYMPTOMS
Figure 2. Flow chart of sacral/pudendal neuromodulation
from 23.2 ⫾ 12.4 to 1.3 ⫾ 2.63 (Wilcoxon test, p ⬍0.05). Mean ⫾ SD incontinence volume decreased from 227 ⫾ 139.1 gm to 3.1 ⫾ 3.1 gm (Wilcoxon test, p not significant). In patients presenting with urgency or
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residual volume, improvement was not statistically significant due to low patient numbers. In patients requiring CIC mean daily frequency of catheterization decreased from 5.2 ⫾ 1.6 to 2.0 ⫾ 1.9 (Wilcoxon test, p ⬍0.05). In 2 patients presenting with encopresis and in 1 presenting with enuresis as associated complaints these conditions resolved with IPG (fig. 3). Complications were observed in 10 patients, with infection noted in 2, dislocation/loss of effect in 6 and pain at the implantation site in 2. Eight patients underwent reoperation for complications, consisting of infection in 2 and dislocation/ loss of effect in 6. Two patients required reintervention because of battery depletion, which should not be considered a complication, but rather a sign of success (long-term use of the battery). At the end of the study 6 of 15 patients (40%) had a full response and 5 (33%) had a partial response, while the IPG devices were explanted because of failure in 4 (27%). As mentioned previously, patients underwent sacral nerve modulation for 4 different indications, ie OAB, DES, Fowler syndrome and neurogenic bladder. Three of 4 patients in the OAB group suffered from severe incontinence. These patients pre-
Figure 3. Symptoms present before treatment with external (test) and internal (implantable) pulse generator. LUTS, lower urinary tract symptoms.
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SACRAL NEUROMODULATION IN CHILDREN WITH URINARY SYMPTOMS
sented with mean ⫾ SD daily incontinence episodes of 4.3 ⫾ 1.53 with a mean ⫾ SD total daily volume of 142 ⫾ 51.6 gm. Mean ⫾ SD daily incontinence episodes were improved to 2.4 ⫾ 1.25 and volume to 4.8 ⫾ 2.84 gm with the test stimulator. After definitive IPG implantation 2 of 3 patients had a full response regarding incontinence, and enuresis resolved in 1. Urgency symptoms resolved in 3 of 4 patients. In this group all 4 patients had suffered from recurrent UTIs before IPG, and none had recurrence after IPG. In the 2 patients with DES mean ⫾ SD daily voiding frequency improved from 8 ⫾ 1 to 6.2 ⫾ 0.21. Post-void residual volume decreased from 360 to 30 ml in 1 patient, resulting in a dramatic decrease in the number of UTIs. In the remaining patient postvoid residual volume decreased less dramatically, although pelvic pain and dysuria resolved. In the 7 patients with Fowler syndrome incontinence and need for CIC were the main criteria for implantation. Three patients had a full response to SNM for incontinence, 2 had a partial response and 2 did not meet implantation criteria. Urinary retention requiring daily CIC was present in 3 subjects, of whom 1 achieved cure and could stop CIC entirely. Of the 5 patients with neurogenic bladder 3 suffered from urinary incontinence, 2 from enuresis, 2 from encopresis and 4 from recurrent UTIs. In all 3 patients with MMC the IPG was removed because of disappointing results. The patient with anal atresia had a full response, with greater than 90% decrease
in incontinence episodes, and the patient with Guillain-Barre syndrome had less urgency, incontinence and enuresis (see table).
DISCUSSION In a highly selected patient population suffering with extreme therapy resistant lower urinary tract conditions we could achieve a full response in 50% (9 of 18 patients) and a partial response in 28% (5) using SNM. This outcome can be considered an encouraging result for a patient population with no remaining treatment options. The success rate might increase with more selective use of SNM for specific indications. Subgroup analysis was performed to detect patient characteristics/indications favorable for good outcomes. Results for overactive bladder, dysfunctional elimination syndrome, Fowler syndrome and neurogenic bladder were compared. A positive experience for overactive bladder, Fowler syndrome and DES was observed. The results for DES confirm the findings of Humphreys et al,2 who observed 16% resolution and 68% improvement of incontinence. The series of Roth at al demonstrated a higher success rate, with complete resolution of incontinence in 75% of cases.3 The experience with MMC as a cause of neurogenic bladder was disappointing in our study and confirmed the results of Guys et al, who found no statistical difference in a prospective study comparing IPG implantation in 21 patients
Patient data Implantation Criteria
Pt No.
Diagnosis
1 2
MMC Guillain-Barre syndrome
Not met Urgency
3
OAB
Incontinence
4 5 6 7
MMC Anal atresia Fowler syndrome Fowler syndrome
Incontinence Incontinence Not met Need for CIC
8
Fowler syndrome
Incontinence
Fowler Fowler Fowler MMC DES DES Fowler OAB OAB OAB
Not met Incontinence Incontinence Incontinence Residual vol Residual vol Incontinence Incontinence Incontinence Frequency
9 10 11 12 13 14 15 16 17 18
syndrome syndrome syndrome
syndrome
Neuromodulation Type Pudendal nerve stimulation S3, revision to pudendal nerve stimulation Pudendal nerve stimulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation, revision to S3 sacral neuromodulation contralateral unsuccessful, revision to pudendal nerve stimulation successful Revision to pudendal nerve stimulation unsuccessful S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation S3 sacral neuromodulation Revision to pudendal nerve stimulation Revision to pudendal nerve stimulation Revision S3 sacral neuromodulation
Results Failure Partial response Full response, infection/explantation, new pudendal nerve stimulation implant contralateral Failure Full response, long-term full response Failure Full response, long-term response
Partial response, failure after revision Failure Full response, no revisions Partial response Partial response, infection, failure after new implant Partial response Full response Full response, long-term failure Full response, full response after revision Full response, initial full response after revision, long-term failure Full response, persistent enuresis
SACRAL NEUROMODULATION IN CHILDREN WITH URINARY SYMPTOMS
with MMC and controls.5 Similar results were observed in adults with neurogenic bladder in the series by Hohenfellner et al, who described 27 test stimulations and 11 IPG implantations.14 Unfortunately the reoperation rate in our series was high, mainly because of lead dislocation and infection. The high dislocation rate (6 of 15 cases) was cumbersome and probably the result of growth and more active movement in children compared to adults. Efforts should be made to improve the tined lead and adapt it for use in children. The infection rate was 13% (2 of 15 patients) and could be explained in 1 patient by the extended test period and 2-stage procedure. However, the test interval was not significantly longer in patients with an infection (Mann-Whitney test, p ⫽ 0.2). Nevertheless, efforts should be made to keep the interval as short as possible to prevent infection of the implant.
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The limitations of this study were the heterogeneity of population and the retrospective character, with less standardized followup compared to a prospective study. Therefore, a prospective study is actually planned based on the encouraging results of this retrospective series.
CONCLUSIONS Sacral neuromodulation is feasible in a pediatric population, with good short-term (78% full or partial response) and satisfactory long-term results (73%). Overactive bladder, DES and Fowler syndrome are promising indications. Neurogenic bladder caused by MMC is probably a less promising indication. Pudendal nerve stimulation is a feasible salvage solution and can be useful in cases when S3 implantation is impossible or unsuccessful.
REFERENCES 1. De Gennaro M, Capitanucci ML, Mosiello G et al: Current state of nerve stimulation technique for lower urinary tract dysfunction in children. J Urol 2011; 185: 1571.
6. Haddad M, Besson R, Aubert D et al: Sacral neuromodulation in children with urinary and fecal incontinence: a multicenter, open label, randomized, crossover study. J Urol 2010; 184: 696.
2. Humphreys MR, Vandersteen DR, Slezak JM et al: Preliminary results of sacral neuromodulation in 23 children. J Urol 2006; 176: 2227.
7. Hoebeke PB, Renson C, De Schryver M et al: Prospective evaluation of clinical voiding reeducation or voiding school for lower urinary tract conditions in children. J Urol 2011; 186: 648.
3. Roth TJ, Vandersteen DR, Hollatz P et al: Sacral neuromodulation for the dysfunctional elimination syndrome: a single center experience with 20 children. J Urol 2008; 180: 306. 4. McGee SM, Routh JC, Granberg CF et al: Sacral neuromodulation in children with dysfunctional elimination syndrome: description of incisionless first stage and second stage without fluoroscopy. Urology 2009; 73: 641. 5. Guys JM, Haddad M, Planche D et al: Sacral neuromodulation for neurogenic bladder dysfunction in children. J Urol 2004; 172: 1673.
8. Hoebeke PB, Renson C, Petillon L et al: Percutaneous electrical nerve stimulation in children with therapy resistant nonneuropathic bladder sphincter dysfunction: a pilot study. J Urol 2002; 168: 2605. 9. Hoebeke PB, Van Laecke E, Everaert K et al: Transcutaneous neuromodulation for the urge syndrome in children: a pilot study. J Urol 2001; 166: 2416. 10. Spinelli M, Giardiello G, Arduini A et al: New percutaneous technique of sacral nerve stimula-
tion has high initial success rate: preliminary results. Eur Urol 2003; 43: 70. 11. Spinelli M, Giardiello G, Gerber M et al: New sacral neuromodulation lead for percutaneous implantation using local anesthesia: description and first experience. J Urol 2003; 170: 1905. 12. Spinelli M, Malaguti S, Giardiello G et al: A new minimally invasive procedure for pudendal nerve stimulation to treat neurogenic bladder: description of the method and preliminary data. Neurourol Urodyn 2005; 24: 305. 13. Scheepens WA, Weil EH, van Koeveringe GA et al: Buttock placement of the implantable pulse generator: a new implantation technique for sacral neuromodulation—a multicenter study. Eur Urol 2001; 40: 434. 14. Hohenfellner M, Humke J, Hampel C et al: Chronic sacral neuromodulation for treatment of neurogenic bladder dysfunction: long-term results with unilateral implants. Urology 2001; 58: 887.
EDITORIAL COMMENT This interesting study adds to the literature evaluating IPG for functional lower urinary tract disorders. The main strength of the study and what differentiates it from others is that the authors categorized the lower urinary tract dysfunction into groups, enabling us to understand how IPG works in different situations. They confirmed that IPG may work for patients with underactive bladder and that it may be used in patients with refractory OAB. Also, they found that IPG failed in 3 patients with MMC. However, despite my belief that the neurogenic cases are unsuitable for this kind of treatment, the small numbers do not allow for any
definitive conclusions to be drawn regarding the level of effectiveness of IPG in these cases. Patients with incomplete neural disease might have a better outcome. The authors showed that at the end of the study 11 of 15 patients had a full or partial response, giving a 73% success rate. However, for the intentto-treat analysis the 3 patients who did not pass through the test phase should also be included for the calculation of the final outcome. When these individuals are included, the success rate decreases to 61%, which is still a good outcome for these difficult cases.
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SACRAL NEUROMODULATION IN CHILDREN WITH URINARY SYMPTOMS
The complication rate was in accordance with that reported in the literature, at around 25%.1 It would be interesting in the future to know the recurrence rate after device deactivation. The rate reported by Roth et al was 60% (3 of 5 cases, reference 3 in article). Finally, I encourage the authors to pursue their research, and I look for-
ward to future updates with more patients and longer follow-up. Ubirajara Barroso, Jr. Federal University of Bahia Bahiana School of Medicine and Public Health Salvador, Brazil
REFERENCE 1. Barroso U Jr, Tourinho R, Lordêlo P et al: Electrical stimulation for lower urinary tract dysfunction: a systematic review of the literature. Neurourol Urodyn 2011; 30: 1429.