Prospective Study of Transcutaneous Parasacral Electrical Stimulation for Overactive Bladder in Children: Long-Term Results

Prospective Study of Transcutaneous Parasacral Electrical Stimulation for Overactive Bladder in Children: Long-Term Results Patrícia Lordêlo, Paulo Vitor Lima Soares, Iza MacIel, Antonio Macedo, Jr. and Ubirajara Barroso, Jr.* From the Department of Urology, Section of Pediatric Urology, Bahiana School of Medicine and Public Health, Salvador-Bahia, Brazil Abbreviations and Acronyms ICCS International Children s Continence Society LUTD lower urinary tract dysfunction OAB overactive bladder TCPSE transcutaneous parasacral electrical stimulation UTI urinary tract infection Submitted for publication April 6, 2009. * Correspondence: Av. Juracy Magalhães Jr., 2096, Sala 306, Salvador-Bahia, Brazil. Purpose: We evaluated the long-term success of transcutaneous parasacral electrical stimulation for overactive bladder in children. Materials and Methods: We prospectively evaluated children who underwent transcutaneous parasacral electrical stimulation for overactive bladder. All patients had symptoms of overactive bladder, bell curve in uroflowmetry and low post-void residual urine. The procedure was performed using a frequency of 10 Hz for 20-minute sessions 3 times weekly for a maximum of 20 sessions. Initial and long-term (more than 6 months) success rates were evaluated. Results: Transcutaneous parasacral electrical stimulation was performed in 36 girls and 13 boys with a mean age of 10.2 years (range 5 to 17). Mean followup was 35.3 months (range 6 to 80). Before treatment urgency, daytime incontinence and urinary tract infection were seen in 100%, 88% and 71% of cases, respectively. Initial success (full response) was demonstrated in 79% of patients for urgency, 76% for incontinence and 77% for all symptoms. Continued success was seen in 84% of patients for urgency, 74% for daytime incontinence and 78% for all symptoms. If the 30 patients with at least 2 years of followup were considered, treatment was successful in 73%. Recurrence of symptoms after a full response was seen in 10% of cases. Two of 33 patients (6%) with urinary tract infection before the procedure still had infection after treatment. Conclusions: Transcutaneous parasacral electrical stimulation is well tolerated, and demonstrates short and long-term effectiveness in treating overactive bladder in children. Symptoms eventually will recur in 10% of patients. Key Words: child; electric stimulation therapy; pelvic floor; urinary bladder, overactive LOWER urinary tract dysfunction is a common problem in children, appearing in about 6% of girls and 3.8% of boys by age 7. 1 This entity is classified as overactive bladder, dysfunctional voiding, postponed voiding and underactive bladder. Overactive bladder is characterized clinically by urgency that may be followed by daytime incontinence, frequency and holding maneuvers. 2 Overactive bladder must be treated due to the association with internalizing and externalizing psychological problems, as well as urinary tract infection and vesicoureteral reflux. 3 5 Recent studies have revealed that many adults with lower urinary tract symptoms had bladder dysfunction as children. 6,7 Traditionally OAB has been treated with anticholinergics. However, their usage is based on nonrandomized 2900 www.jurology.com 0022-5347/09/1826-2900/0 Vol. 182, 2900-2904, December 2009 THE JOURNAL OF UROLOGY Printed in U.S.A. Copyright 2009 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/j.juro.2009.08.058

PARASACRAL ELECTRICAL STIMULATION FOR OVERACTIVE BLADDER 2901 clinical trials and they are associated with a low rate of complete resolution of symptoms. 8 Additionally drug treatment has several drawbacks, including the need for long-term administration, poor compliance and side effects. 9,10 Electrotherapy has emerged as an alternative to treat patients with OAB. However, most published studies have used electrotherapy at sites that are uncomfortable for children (penile, anal and percutaneous sites). 11,12 Hoebeke 13 and Bower 14 et al were the first to use TCPSE in children with LUTS, reporting a good success rate. Nevertheless, their results are confounded by concomitant administration of anticholinergics in many patients. Also, duration of treatment was long (several months), which makes diffusion of the method difficult. Recently we published a pilot study of children with OAB using ambulatory TCPSE at 10 Hz frequency for 20-minute sessions 3 times weekly for a maximum of 20 sessions. 15 In that series no patient took anticholinergics before or during treatment. We observed that 63% of patients had complete symptomatic improvement and 20% had significant improvement. The objective of the current study was to evaluate the long-term results of this ambulatory short course TCPSE. MATERIALS AND METHODS We prospectively evaluated children with OAB symptoms who underwent TCPSE with a minimum followup of 6 months. OAB was defined as presence of urgency with or without urge incontinence, an associated bell curve in uroflowmetry, post-void residual urine less than 10% of expected bladder capacity on ultrasound and more than 3 voids daily recorded in the voiding diary. Post-void residual urine was less than 5 ml in 44 patients, 5 to 20 ml in 3 and not recorded in 2. No child presented with post-void residual urine greater than 20 ml. A rigorous voiding history was taken using a structured nonvalidated questionnaire. The severity of daytime incontinence and nocturnal enuresis was divided into the 4 categories of 5 to 7 episodes, 3 to 4 episodes, 1 to 2 episodes and less than 1 episode weekly. Speech, motor coordination, limb sensitivity, bulbocavernosus and ischiocavernosus reflex, and tonicity of the anal sphincter were routinely examined. The lumbosacral area was evaluated for signs of spina bifida. All children with a suspected neurological disorder were evaluated by a neurologist and excluded from the study, as were those with anatomical anomalies of the lower urinary tract or less than 6 months of followup. TCPSE was performed at the office using 2 superficial 3.5 cm electrodes placed on each side of S3 (see figure), with electrical energy produced by a generator (Dualpex Uro 961, Quark ). A frequency of 10 Hz was used with a generated pulse of 700 s. Frequency was increased to the maximum level tolerated by the child. TCPSE was performed 3 times weekly for 20-minute sessions. Number of Parasacral superficial electrode placement for electrical stimulation. sessions varied according to outcome, with a maximum of 20. One month before TCPSE and during followup we recommended behavioral training consisting of voiding every 3 hours or at onset of desire to void and avoidance of tea, coffee, sodas and chocolate. The training is described in a booklet with illustrations indicating the need to void before sleeping, increase daily volume of ingested liquid, eat foods rich in fiber and avoid postponing voiding when symptoms of urgency are present. Girls are asked to prioritize voiding comfort by avoiding sitting on a toilet seat with an overly large opening. The booklet suggests options of toilet seat adapters and foot supports to adjust for height issues. Only patients who do not improve significantly with this approach progress to TCPSE. To evaluate the effectiveness of the method, caregivers were asked about the presence of OAB symptoms according to ICCS definition, as follows. 2 Initial outcome was defined as nonresponse (0% to 49%), partial response (50% to 89%), significant response (90% or greater) or full response (100%) in decreasing symptoms. Long-term outcome was defined as relapse (symptom recurrence more than monthly), continued success (no relapse at 6 months after treatment) and complete success (no relapse at 2 years after treatment). Outcome concerned only daytime symptom resolution. Persistence of nocturnal enuresis as the only symptom was not considered a failure because it may have a different physiopathological process. Children were asked to return for evaluation 1 month after the last treatment session. Parents were asked to rate symptom improvement as complete, significant, mild or no improvement. Also, parents were asked to rate the percentage of improvement on a scale of 0% to 100%. Return visits were scheduled at 3-month intervals during the first 2 years and 6-month intervals thereafter. Patients who did not return were contacted by telephone.

2902 PARASACRAL ELECTRICAL STIMULATION FOR OVERACTIVE BLADDER RESULTS TCPSE was performed in 36 girls and 13 boys with an average age of 10.2 years (range 5 to 17). Followup ranged from 6 to 80 months (average 35.3). Before treatment all patients presented with symptoms of urgency and holding maneuvers to avoid urinary loss. Of the patients 43 (88%) also had daytime incontinence. Distribution of patients according to daytime incontinence and nocturnal enuresis severity is outlined in table 1. UTI was detected in 35 patients (71%), of whom 54% had 3 or more episodes. Initial Success Two patients did not have outcome registered immediately after treatment. The majority of patients reported a full response for urgency, incontinence and all symptoms. When we asked parents about percentage of symptom improvement 25 reported 100%, 6 reported 90% to 99%, 2 reported 80% to 89%, 3 reported 50% to 59% and 1 reported less than 50% improvement. Data for 12 patients were missing. Long-Term Success Table 2 outlines long-term success of TCPSE. For urgency 41 cases had continued success, 3 had persistent symptoms and 5 improved only after anticholinergics. For daytime incontinence 32 cases had continued success, 3 had significant improvement, 4 had persistent symptoms and 4 had resolution after anticholinergics. Continued resolution of all symptoms was reported in the majority of patients. A small percentage of patients with UTI before TCPSE still had infection after treatment. Nocturnal enuresis was present in 32 patients (65%) before treatment, with 5 to 7 episodes in 21, 3 to 4 episodes in 5, 1 to 2 episodes in 3 and less than 1 episode weekly in 3. Of these patients 24 (75%) had resolution of symptoms and 8 (25%) had persistent symptoms. A total of 30 patients had 2 years or more of followup available. Complete success was reported in 22 patients (73%), while 8 (16%) had relapses. After a full response to TCPSE 3 patients (10%) had symptoms recur soon after the procedure. Table 1. Initial success after TCPSE Symptoms No. Full Response (%) No. Response or Partial Response (%) No. Nonresponse (%) Urgency 37 (79) 3 (6) 7 (15) Incontinence 31 (76) 2 (5) 8 (20) episodes/wk: 5 7 16 (76) 1 (5) 4 (19) 3 4 5 (56) 1 (11) 3 (33) 1 2 6 (100) 0 (0) 0 (0) Less than 1 4 (80) 0 (0) 1 (20) All symptoms 36 (77) 3 (6) 8 (17) Table 2. Long-term success after TCPSE Symptoms No. Continued Success (%) No. Relapse (%) Urgency 41 (84) 8 (16) Incontinence episodes/wk: 32 (74) 11 (26) 5 7 14 (64) 8 (36) 3 4 8 (89) 1 (11) 1 2 5 (83) 1 (17) Less than 1 5 (83) 1 (17) All symptoms 38 (78) 11 (22) Urinary tract infection 33 (94) 2 (6) DISCUSSION This prospective study demonstrates the long-term efficacy of TCPSE in treating OAB symptoms. Anticholinergics were used only when treatment failed. Results of long-term studies of children with LUTD may be criticized because patients may show marked spontaneous improvement of symptoms. Also, continuation of bladder training (urotherapy) in followup sessions could have a positive influence on success rates. However, these results confirm our previous data, in which TCPSE was effective even shortly after the procedure. 15 According to our data, in the first month after treatment the majority of children had a full response for daytime incontinence and urgency. These results were maintained through time. Considering only cases with at least 2 years of followup, 73% had complete success and 27% relapsed. Global rate of UTI after treatment was only 4%. To our knowledge this study of electrical stimulation for children with OAB has the longest reported followup. Caldwell was the first to describe the results of electrical therapy for LUTD in children. 16 However, despite the initial success, invasive techniques of electrical stimulation preclude its widespread use in children. 11,12 Hoebeke 13 and Bower 14 et al reported the first 2 series of TCPSE over S3 for children with OAB. Hoebeke et al evaluated 15 girls and 26 boys. The sessions used a frequency of 2 Hz and were performed daily for 2 hours each for a period of 6 months. The patients studied had not achieved initial significant improvement with other types of treatment for daytime incontinence. Of the patients 13 did not respond to treatment. At 1 year the rate of complete resolution of daytime incontinence was 51.2%. Bower et al applied home TCPSE in 17 children, using 1 or 2 sessions daily with a frequency of 10 to 150 Hz. Of children with daytime urinary incontinence 47% had the symptom resolve. Our series differs from these studies due to the decreased number and duration of sessions (3 times weekly, 20 minutes each), decreased frequency (10 Hz) and lack of medication administered simulta-

PARASACRAL ELECTRICAL STIMULATION FOR OVERACTIVE BLADDER 2903 neously with the procedure. Use of a high frequency of energy (more than 20 Hz) may be hazardous because it excites the neuromotor system, which increases pelvic floor muscle tension. Gladh et al demonstrated in cats that a frequency of 5 to 10 Hz better inhibited bladder function. 11 Our success rate is similar to some series of electrical stimulation and better than others. 11 14 Possible reasons for this discrepancy include differences in study populations (some prior series had less rigid restrictions and included dysfunctional voiding cases, and some included only refractory OAB) and difference in treatment method. As ICCS recommends, our series stratifies type of LUTD and standardizes final measurements. 2 Only patients with OAB were included in the study. All patients exhibited urgency, the hallmark symptom of OAB, and also had a coordinating void. The outcome was also evaluated using the ICCS recommendation, which allows comparison with other series. No side effects were detected in our study, and compliance with treatment was good. Usually children experience a tolerable pins and needles sensation in the sacral area. When a child reports any uncomfortable sensation the intensity of the stimulus is reduced. A limitation of our study is the lack of a control group. However, we performed a randomized clinical trial comparing children with OAB who underwent TCPSE (test group) with a sham group (control group) who underwent scapular stimulation. 17 All patients underwent 20 sessions of 20 minutes each, 3 times weekly. A total of 33 patients completed treatment (test group 19, sham group 14). In the test group 63.2% and 37.8% of parents, respectively, reported complete resolution and significant improvement of symptoms. In the sham group complete resolution and significant improvement were reported by 0% and 21.4%, respectively (p 0.001). Toronto score improved significantly in the test group and did not improve in the sham group. The mechanism of action of electrical stimulation for OAB has not been established, but we know that it acts directly on the muscle fibers as well as the reflexes. 18 One theory is that electrical stimulation would inhibit the detrusor contraction by activating the sympathetic plexus or inhibiting the parasympathetic neurons. 19 The reflexogenic mechanism of action of intracavitary electrical stimulation has been observed in animals. 20 22 However, recent studies have revealed a supraspinal action of electrical stimulation. Liao et al investigated whether brain reorganization occurred along with clinical improvement after sacral root stimulation. 23 Six patients 33 to 68 years old with idiopathic OAB were included in the study. All exhibited clinical improvement after sacral root stimulation. Transcranial magnetic stimulation was applied to study motor cortex excitability and the brain mapping of the muscle. Motor cortex excitability and area of representation for the flexor hallucis brevis muscle increased for at least 30 minutes after sacral root stimulation was terminated. These results show that sustained sacral root stimulation may reorganize the human brain and its ability to excite the motor cortex, modulating lower urinary tract function. CONCLUSIONS TCPSE is a well tolerated and effective method for treating OAB in children in short and long-term followup. Rate of complete response with this treatment is about 73%. Only 6% of patients with a history of UTI still had infection after the procedure. We expect that 10% of the patients will have recurrence of OAB symptoms after TCPSE with time. REFERENCES 1. Hellstrom AL, Hanson E, Hansson S et al: Micturition habits and incontinence in 7-year-old Swedish school entrants. Eur J Pediatr 1990; 149: 434. 2. Neveus T, von Gontard A, Hoebeke P et al: The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children s Continence Society. J Urol 2006; 176: 314. 3. von Gontard A, Lettgen B, Olbing H et al: Behavioural problems in children with urge incontinence and voiding postponement: a comparison of a paediatric and child psychiatric sample. Br J Urol, suppl., 1998; 81: 100. 4. Koff SA, Lapides J and Piazza DH: Association of urinary tract infection and reflux with uninhibited bladder contractions and voluntary sphincteric obstruction. J Urol 1979; 122: 373. 5. Barroso U Jr, Jednak R, Barthold JS et al: Outcome of ureteral reimplantation in children with the urge syndrome. J Urol 2001; 166: 1031. 6. Fitzgerald MP, Thom DH, Wassel-Fyr C et al: Childhood urinary symptoms predict adult overactive bladder symptoms. J Urol 2006; 175: 989. 7. Minassian VA, Lovatsis D, Pascali D et al: Effect of childhood dysfunctional voiding on urinary incontinence in adult women. Obstet Gynecol 2006; 107: 1247. 8. Sureshkumar P, Bower W, Craig JC et al: Treatment of daytime urinary incontinence in children: a systematic review of randomized controlled trials. J Urol 2003; 170: 196. 9. Youdim K and Kogan BA: Preliminary study of the safety and efficacy of extended release oxybutynin in children. Urology 2002; 59: 428. 10. Nijman RJ: Role of antimuscarinics in the treatment of nonneurogenic daytime urinary incontinence in children. Urology 2004; 63: 45. 11. Gladh G, Mattsson S and Lindstrom S: Anogenital electrical stimulation as treatment of urge incontinence in children. BJU Int 2001; 87: 366. 12. De Gennaro M, Capitanucci ML, Mastracci P et al: Percutaneous tibial nerve neuromodulation is

2904 PARASACRAL ELECTRICAL STIMULATION FOR OVERACTIVE BLADDER well tolerated in children and effective for treating refractory vesical dysfunction. J Urol 2004; 171: 1911. 13. Hoebeke P, Van Laecke E, Everaert K et al: Transcutaneous neuromodulation for the urge syndrome in children: a pilot study. J Urol 2001; 166: 2416. 14. Bower WF, Moore KH and Adams RD: A pilot study of the home application of transcutaneous neuromodulation in children with urgency or urge incontinence. J Urol 2001; 166: 2420. 15. Barroso U Jr, Lordelo P, Lopes AA et al: Nonpharmacological treatment of lower urinary tract dysfunction using biofeedback and transcutaneous electrical stimulation: a pilot study. BJU Int 2006; 98: 166. 16. Caldwell KP, Martin MR, Flack FC et al: An alternative method of dealing with incontinence in children with neurogenic bladders. Arch Dis Child 1969; 44: 625. 17. Barroso U, Teles A, Veiga ML et al: Superficial parasacral electrical stimulation to overactive bladder in children. A randomized clinical trial. Presented at annual meeting of European Society of Pediatric Urology, Amsterdam, The Netherlands, May 6 9, 2009. 18. Trontelj JV, Janko M, Godec C et al: Electrical stimulation for urinary incontinence: a neurophysiological study. Urol Int 1974; 29: 213. 19. Godec C, Cass AS and Ayala GF: Bladder inhibition with functional electrical stimulation. Urology 1975; 6: 663. 20. Lindstrom S, Fall M, Carlsson CA et al: The neurophysiological basis of bladder inhibition in response to intravaginal electrical stimulation. J Urol 1983; 129: 405. 21. Sundin T and Carlsson CA: Reconstruction of severed dorsal roots innervating the urinary bladder. An experimental study in cats. I. Studies on the normal afferent pathways in the pelvic and pudendal nerves. Scand J Urol Nephrol 1972; 6: 176. 22. Sundin T, Carlsson CA and Kock NG: Detrusor inhibition induced from mechanical stimulation of the anal region and from electrical stimulation of pudendal nerve afferents. An experimental study in cats. Invest Urol 1974; 11: 374. 23. Liao KK, Chen JT, Lai KL et al: Effect of sacralroot stimulation on the motor cortex in patients with idiopathic overactive bladder syndrome. Neurophysiol Clin 2008; 38: 39 EDITORIAL COMMENTS I congratulate the authors on a nice study with good long-term followup. There are several issues that could have been addressed but were lacking. The explanation regarding how this treatment modality works is interesting but the references cited date back to the early 1970s. Much has been learned since then, especially with newer neuroimaging techniques in humans. One wonders whether the authors would have had the same success rate as other studies cited if they had treated the same class of patients (references 12 to 14 in article). Does the 26% incontinence rate at 2 years apply to the same class of patients the other authors were dealing with when they began treatment? This is an important question that will need to be answered in future studies. What is appealing and intriguing is that a large number of patients responded to this treatment and remained symptom-free without medications. If we see this modality as modifying supraspinal pathways or in the simplest form, it may just be leading to a reduction of urgency during the treatment period. It may be that elimination of the urgency (guarding reflex) leads to normalization of voiding without the presence of abnormally increased outlet resistance, and the eventual return of normal detrusor and/or possibly up-regulated receptors and/or neurotransmitters in the bladder or spinal cord. Israel Franco Department of Urology New York Medical College Valhalla, New York This report concerns the prospective study of transcutaneous parasacral electrical stimulation to treat symptoms of overactive bladder in children. The significance of the article is that it is a long-term study from a series first published in 2006. The parasacral cutaneous pads and use of transcutaneous electrical nerve stimulation at 10 Hz 3 times weekly for 20 minutes for a maximum of 20 sessions is significantly less onerous than previously published studies. The authors report success rates for the symptoms of overactive bladder in the 70% or better range, which is an improvement over recently published studies. The results are based on reported percentile improvements in symptoms of overactive bladder rather than strict urodynamic criteria. They recognize the lack of strict science that might have been derived from followup urodynamics but suggest that patient satisfaction may be more critical in this group. Additionally although there is no specific placebo group in this series, the authors interestingly compared the parasacral group to a group of patients who underwent scapular stimulation, and observed a clear benefit in the former. A possible weakness of the study was that cases with successful stimulation were continued on conservative management (bladder training). One wonders whether the positive effects seen in the long term were due to conservative urotherapy in addition to stimulation. The 2-year followup and excellent results achieved with this therapy are noteworthy. This technique may be helpful in patients with failed conservative urotherapy for overactive bladder. William E. Kaplan Division of Pediatric Urology Northwestern University Feinberg School of Medicine Chicago, Illinois