- Email: [email protected]
Transcutaneous Parasacral Electrical Neural Stimulation in Children with Primary Monosymptomatic Enuresis: A Prospective Randomized Clinical Trial
Transcutaneous Parasacral Electrical Neural Stimulation in Children with Primary Monosymptomatic Enuresis: A Prospective Randomized Clinical Trial Liliana Fajardo de Oliveira, Dayana Maria de Oliveira, Lidyanne Ilı´dia da Silva de Paula, Avarese de Figueiredo, Jose de Bessa, Jr., Cacilda Andrade de Sa Andre Murillo Bastos Netto* and Jose From the Department of Surgery, Division of Urology, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais (DMdO, LIdSdP, AAdF, CAdS, JMBN) and Department of Surgery, Division of Urology, State University of Feira de Santana, Feira de Santana, Bahia (JdB), Brazil
Purpose: Parasacral transcutaneous electrical neural stimulation is widely used to treat hyperactive bladder in children and adults. Its use in nonmonosymptomatic enuresis has demonstrated improvement in number of dry nights. We assessed the effectiveness of parasacral transcutaneous electrical neural stimulation in the treatment of monosymptomatic primary enuresis. Materials and Methods: This prospective randomized clinical trial included 29 girls and 16 boys older than 6 years with primary monosymptomatic enuresis. Children were randomly divided into 2 groups consisting of controls, who were treated with behavioral therapy, and an experimental group, who were treated with behavioral therapy plus 10 sessions of parasacral transcutaneous electrical neural stimulation. Neural stimulation was performed with the electrodes placed in the sacral region (S2/S3). Sessions always followed the same pattern, with duration of 20 minutes, frequency of 10 Hz, a generated pulse of 700 ms and intensity determined by the sensitivity threshold of the child. Sessions were done 3 times weekly on alternate days. Patients in both groups were followed at 2-week intervals for the first month and then monthly for 6 consecutive months. Results: Rate of wet nights was 77% in controls and 78.3% in the experimental group at onset of treatment (p ¼ 0.82), and 49.5% and 31.2%, respectively, at the end of treatment (p ¼ 0.02). Analyzing the average rate of improvement, there was a significantly greater increase in dry nights in the group undergoing neural stimulation (61.8%) compared to controls (37.3%, p ¼ 0.0038). At the end of treatment percent improvement in children undergoing electrical stimulation had no relation to gender (p ¼ 0.391) or age (p ¼ 0.911). Conclusions: Treatment of primary monosymptomatic enuresis with 10 sessions of parasacral transcutaneous electrical neural stimulation plus behavioral therapy proved to be effective. However, no patient had complete resolution of symptoms.
Abbreviations and Acronyms CG ¼ control group EG ¼ experimental group ICCS ¼ International Children’s Continence Society PTENS ¼ parasacral transcutaneous electrical neural stimulation Accepted for publication March 26, 2013. Funded by CNPQeConselho Nacional de Pesquisa e Desenvolvimento (National Council for Research and Development) and by FAPEMIGeFundac‚~ao de Amparo a Pesquisa do Estado de Minas Gerais (Research Foundation of the State of Minas Gerais, Brazil). Study received approval of institutional ethics committee in clinical research. * Correspondence: Av. Rio Branco, 2985/sl. 605, Juiz de Fora, Minas Gerais, Brazil 36010012 (telephone: 55-32-3218-9899; FAX: 55-32-32189899; e-mail: [email protected]).
Key Words: behavior therapy, electric stimulation therapy, enuresis, transcutaneous electric nerve stimulation, urinary incontinence
ENURESIS is defined by the International Children’s Continence Society as intermittent urinary incontinence
that occurs during sleep.1,2 Although the condition has been described for thousands of years, none of the
0022-5347/13/1904-1359/0 THE JOURNAL OF UROLOGY® © 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.03.108 Vol. 190, 1359-1363, October 2013 Printed in U.S.A.
www.jurology.com
j
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treatments currently available is sufficiently effective, perhaps due to lack of knowledge about the etiology, intervening factors, and lack of uniformity regarding concepts and definitions.3,4 Current therapeutic modes consist of medical treatment with desmopressin, imipramine or oxybutynin, and use of alarms and behavioral therapy, in which changes in the daily routine related to urination are recommended.5e8 Of the treatments described the best long-term results are achieved with alarms, with a success rate of about 77%,9 followed by desmopressin, with a complete response of approximately 37%.10 Daytime incontinence in children is usually due to overactive bladder, and treatment with PTENS is an option that can achieve excellent results.1114 A recent systematic review showed a scarcity and lack of uniformity in the parameters of PTENS in the treatment of overactive bladder.15 It is believed that PTENS has an effect on physiological reconditioning, which enables remodulation of synapses through the mechanism of neuroplasticity, hopefully achieving neural reconditioning.16 Its therapeutic effect is achieved through the recovery of cerebral activity associated with self-regulation and attenuation of activity of the cingulate gyrus, reinnervating the muscle fibers, which are partly denervated.16 To our knowledge parasacral transcutaneous eletrical neural stimulation has never been tested in the treatment of monosymptomatic enuresis. However, it has been used in nonmonosymptomatic enuresis, with improvement in number of dry nights in 63% of children and complete resolution of symptoms in 42%.17 Up to 30% of children with enuresis display nocturnal bladder overactivity.18 Due to the satisfactory results of PTENS in patients with daytime incontinence caused by overactive bladder and in those with nonmonosymptomatic enuresis,1115,17 we evaluated the efficacy of PTENS in the treatment of patients with primary monosymptomatic enuresis.
MATERIALS AND METHODS In this randomized prospective clinical trial we evaluated children older than 6 years with primary monosymptomatic enuresis. Diagnosis was made by clinical history, physical examination and voiding diary. Urinalysis was used to exclude urinary tract infection. Exclusion criteria were age younger than 6 years, presence of nonmonosymptomatic or secondary enuresis, history of treatment for enuresis within 6 months before entering the study and the presence of neurological, psychiatric or renal disease. Patients excluded from the study were followed and treated at our enuresis clinic and received other treatments for enuresis. The study was approved by the ethics committee in clinical research of our institution, and individuals responsible for the children signed an informed consent.
At the first clinical appointment a standardized clinical interview was done, consisting of questions about general health status and urinary symptoms to understand the characteristics of the enuresis. Also the parents were instructed to keep a voiding diary to help classify the enuresis as monosymptomatic or nonmonosymptomatic by evaluating frequency, bladder volumes and presence of urgency or incontinence. To quantify the number of wet nights, and to represent a start point marker for evolution and efficacy of treatment, we used a diary of wet nights in which the participants were instructed to write down the episodes of enuresis for 2 weeks before beginning treatment. Urinalysis was done to rule out urinary tract infection. Only after assessment of these data were the children randomized into 2 groups using Research Randomizer (http://www.randomizer.org). Children in the CG underwent behavioral therapy. These orientations consisted of guidance about decreasing evening liquid intake and avoiding liquids 2 hours before bedtime, curbing intake of foods and liquids containing caffeine, keeping a diary of dry nights, use of rewards for dry nights and bladder training consisting of emptying the bladder before going to bed, immediately after waking up and every 3 to 4 hours during the day, regardless of need or desire to urinate.9,19 These orientations were verbally reinforced at every clinical visit after beginning treatment (biweekly for the first month and monthly for the next 6 months) and were also printed at the back of the diary of wet nights. Children in the EG likewise underwent behavioral therapy and also underwent PTENS using a Neurodyn Evolution electrical stimulator (Ibramed, Amparo, S~ ao Paulo, Brazil). The treatment was carried out in a reserved room with the children accompanied by their parents. The child was put in the prone position and 2 electrodes were placed in the sacral region at the S2/S3 vertebral level on opposite sides of the lumbar column. The sessions lasted 20 minutes under a frequency of 10 Hz, pulse width of 700 mS and intensity determined by the sensitivity threshold of the child. A total of 10 sessions were done 3 times weekly on alternate days.12,17,20 During PTENS sessions no reinforcement of orientations was done. After completing the 10 sessions the patients were followed and reassessed every 2 weeks for the first month and monthly during the subsequent 6 months. The results were evaluated according to the ICCS standardization,1,2 in which decrease of wet nights by less than 50% signifies absence of response, reduction by 50% to 89% constitutes partial response and decrease by more than 89% indicates response. To calculate the average rate of improvement in wet nights in each group, we used the formula, improvement in % ¼ [100 e (wet days after treatment/wet days before treatment)]. Continuous variables were analyzed using the Student t test and Mann-Whitney U test. Fisher exact test was used for comparison of categorical data. Results were considered statistically significant at p <0.05.
RESULTS A total of 45 children with primary monosymptomatic enuresis were enrolled in the study,
PARASACRAL ELECTRICAL NERVE STIMULATION FOR MONOSYMPTOMATIC ENURESIS
with 18 (6 boys) in control group and 27 (10 boys) in experimental group. Mean SD age was 9.9 2.7 years (range 6.2 to 16.3) in the CG and 9.8 2.9 years (6.3 to 14.1) in the EG (p ¼ 0.92). In the CG boys had a mean age of 9.9 2.7 years and girls 9.8 2.9 years (p ¼ 0.94). In the EG boys had a mean age of 9.6 2.7 years and girls 10.0 3.2 years (p ¼ 0.70). All children completed the voiding diary and attended all scheduled clinic visits. Percentage of wet nights before treatment was 77.0% in the CG and 78.3% in the EG (p ¼ 0.82). After 6 months of followup these percentages decreased to 49.5% and 31.2%, respectively (p ¼ 0.02, fig. 1). Improvement in wet nights was 37.3% in the CG and 61.8% in the EG (p ¼ 0.0038, fig. 2). According to ICCS standardization criteria, we observed that 15% of patients in the EG responded to treatment, while 56% displayed partial response and 30% had no response. Meanwhile, in the CG these percentages were 6%, 33% and 61%, respectively. No patient in either group had complete resolution of symptoms (fig. 3). When assessed by age, in the EG the rate of wet nights before treatment was 66.7% in children older than 10 years and 79.6% in children 10 years or younger (p ¼ 0.693). After treatment these rates were 29.7% and 32.7%, respectively (p ¼ 0.911). When assessed by gender, the rate of wet nights before treatment was 88.0% in boys and 72.6% in girls (p ¼ 0.032). At the end of 6 months of followup these rates were 36.7% and 28.0%, respectively (p ¼0.391).
DISCUSSION Studies of monosymptomatic enuresis have progressed steadily. However, to date, no treatment proposed for resolution of enuresis has been observed to be completely effective, with more than a third of patients exhibiting an unsatisfactory
Figure 1. Percentage of wet nights in each group during treatment. d, days.
1361
Figure 2. Percentage of improvement in wet nights (p ¼ 0.0038)
response.17,21 Thus, we sought a new treatment modality for primary monosymptomatic enuresis, which is painless and carries no side effects. We observed that the combination of PTENS and behavioral therapy decreases the percentage of wet nights compared to behavioral therapy alone in children with monosymptomatic enuresis. This positive result can also be confirmed through analysis of average percent improvement, a variable created to better visualize the final results. According to this variable, children in the CG had an average percent improvement of 37.3%, while those undergoing PTENS and behavioral therapy had a 61.8% improvement, confirming the efficacy of this method (p ¼ 0.0038). The use of PTENS in children with enuresis was first applied by Lord^elo et al in 2010.17 Their study included only children with nonmonosymptomatic enuresis and verified that 42% of the patients were dry, 21% exhibited significant improvement of symptoms, 32% did not display any changes and 5%
Figure 3. Treatment response according to ICCS standardization.1,2 Absence of response indicates decrease of wet nights by less than 50%, partial response reduction by 50% to 89% and response decrease by more than 89%.
1362
PARASACRAL ELECTRICAL NERVE STIMULATION FOR MONOSYMPTOMATIC ENURESIS
had worsening of symptoms after treatment. Despite the positive results of PTENS, in addition to enuresis the children had daytime symptoms, unlike the present study, in which we evaluated only children with monosymptomatic enuresis. Improvement of daytime overactive bladder symptoms with PTENS has already been well documented, and with the resolution of overactive bladder contractions many children stop wetting the bed.12,17 By comparison, a study evaluating behavioral therapy in 23 children revealed that the number of enuretic episodes decreased by at least 1 night per week in 16 (70%), wet nights were reduced by at least 50% in 9 (39%) and full recovery was observed in 5 (22%), demonstrating the lack of sufficient effectiveness of behavioral therapy alone.22 Despite the fact that the etiology of enuresis is not well understood, it is known that nocturnal continence depends on 3 factors, namely production of nocturnal urine (nocturnal polyuria), nocturnal bladder function (nocturnal bladder overactivity), and sleep and arousal mechanisms. Therefore, any child will display enuresis if he or she produces a larger volume of urine than normal bladder capacity and/or has nocturnal detrusor overactivity associated with the inability to wake up with imminent bladder contraction and desire to void.23 These factors can be caused by an alteration of the brainstem.24 Treatment with behavioral therapy would mainly act on extrinsic factors of the body, since changes in food ingestion and habits (sleeping, voiding) would produce secondary effects on the body, normalizing bladder function through active cooperation of the child.22 By comparison, PTENS would act directly on the neurological system, resulting in physiological changes with consequent neural reconditioning. Thus, it is believed that the results observed at the end of treatment are due to the fact that the combination of the 2 therapies benefits children with enuresis by acting on different etiological factors. However, new studies must be done in this field to further confirm the efficacy of this approach. In the present study neither gender nor age influenced the effects of PTENS on improving percentage of wet nights. One would imagine that age might be a determining factor in treatment, since older children are more mature, which would enable them to follow the instructions more thoroughly
with consequent better participation and execution of the orientations. These children also show less dependency on their parents for supervision and are not affected as much if the parents cannot guide them through the training process. Complete resolution of enuresis was not found in any child in the EG after 6 months of monitoring, and 1 child (5.6%) did not display any change in symptoms, with the remainder achieving at least some improvement. The combination of PTENS and behavioral therapy in the experimental group was chosen because the recommendations used in behavioral therapy are always used when treating enuresis. It is important to add that despite the positive results found in this study, the number of sessions performed (10) might not have been enough to achieve better neuromodulation and, consequently, better results. We believe that with a greater number of PTENS sessions the results would have been better, which opens the way for new studies. Another possible flaw of the study is that children undergoing PTENS had constant contact with the researcher (3 times weekly for 10 sessions), while children treated with behavioral therapy alone had contact with a health professional only at their monthly appointment. Therefore, the clinical significance of the difference found in the outcomes between groups might be narrow, since achieving good results with behavioral therapy depends on the number of visits to professionals. To our knowledge this is the first study in which PTENS was used to treat children with monosymptomatic nocturnal enuresis. Our results, although consisting of partial response in the majority of cases, open the way for new research in this field and establish PTENS as a new therapeutic method for treating children with enuresis.
CONCLUSIONS In children with primary monosymptomatic enuresis PTENS plus behavioral therapy decreased the number of wet nights more than behavioral treatment alone. However, no patient in our series had a complete response to treatment. Therefore, new studies using PTENS for longer periods or in combination with other therapeutic modalities are needed to better understand its role in the treatment of enuresis.
REFERENCES 1. 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.
2. Neveus T, Eggert P, Evans J et al: Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International
PARASACRAL ELECTRICAL NERVE STIMULATION FOR MONOSYMPTOMATIC ENURESIS
Children’s Continence Society. J Urol 2010; 183: 441.
randomized crossover study. J Urol 2010; 184: 2521.
3. Hellstr€om AL, Hanson E, Hansson S et al: Micturition habits and incontinence in 7-year-old Swedish school entrants. Eur J Pediatr 1990; 149: 434.
11. Barroso U Jr, Lord^elo 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.
4. Hj€amas K: Enuresis in children. Int Braz J Urol 2002; 28: 232. 5. Stenberg A and L€ackgren G: Desmopressin tablets in the treatment of severe nocturnal enuresis in adolescents. Pediatrics 1994; 94: 841. 6. Rappaport L: Prognostic factors for alarm treatment. Scand J Urol Nephrol Suppl 1997; 183: 55. 7. Houts AC: Nocturnal enuresis as a biobehavioral problem. Behav Ther 1991; 22: 133.
12. Barroso U Jr, Teles A, Veiga ML et al: Superficial parasacral electrical stimulation to overactive bladder in children. A randomized clinical trial. J Pediatr Urol, suppl., 2009; 5: S74. 13. Humphreys MR, Vandersteen DR, Slezak JM et al: Preliminary results of sacral neuromodulation in 23 children. J Urol 2006; 176: 2227.
8. Zaffanello M, Giacomello L, Brugnara M et al: Therapeutic options in childhood nocturnal enuresis. Minerva Urol Nefrol 2007; 59: 199.
14. Siegel SW, Catanzaro F, Dijkema HE et al: Longterm results of a multicenter study on sacral nerve stimulation for treatment of urinary urge incontinence, urgency-frequency, and retention. Urology, suppl., 2000; 56: 87.
9. Houts AC: Behavioral treatment for enuresis. In: Evidence-Based Psychotherapies for Children and Adolescents. Edited by AE Kazdin and JR Weisz. New York: Guilford Press 2003; p 389.
15. Barroso U Jr, Tourinho R, Lord^elo P et al: Electrical stimulation for lower urinary tract dysfunction in children: a systematic review of the literature. Neurourol Urodyn 2011; 30: 1429.
10. Kwak KW, Lee YS, Park KH et al: Efficacy of desmopressin and enuresis alarm as first and second line treatment for primary monosymptomatic nocturnal enuresis: prospective
16. Dasgupta R, Critchley HD, Dolan RJ et al: Changes in brain activity following sacral neuromodulation for urinary retention. J Urol 2005; 174: 2268.
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17. Lord^elo P, Benevides I, Kerner EG et al: Treatment of non-monosymptomatic nocturnal enuresis by transcutaneous parasacral electrical nerve stimulation. J Pediatr Urol 2010; 6: 486. 18. Hj€almas K, Arnold T, Bower W et al: Nocturnal enuresis: an international evidence based management strategy. J Urol 2004; 171: 2545. 19. Fowler CJ: Integrated control of lower urinary tractdclinical perspective. Br J Pharmacol, suppl., 2006; 147: S14. 20. Fall M and Lindstr€om S: Transcutaneous electrical nerve stimulation in classic nonulcer interstitial cystitis. Urol Clin North Am 1994; 21: 131. 21. Meneses RP: Monosymptomatic nocturnal enuresis. J Pediatr (Rio J) 2001; 77: 161. 22. Robson LM and Leung AK: Urotherapy recommendations for bedwetting. J Natl Med Assoc 2002; 94: 577. 23. Neveus T, L€ackgren G, Tuvemo T et al: Enuresis: background and treatment. Scand J Urol Nephrol Suppl 2000; 206: 1. 24. Neveus T: Nocturnal enuresisdtheoretic background and practical guidelines. Pediatr Nephrol 2011; 26: 1207.
Purpose: Parasacral transcutaneous electrical neural stimulation is widely used to treat hyperactive bladder in children and adults. Its use in nonmonosymptomatic enuresis has demonstrated improvement in number of dry nights. We assessed the effectiveness of parasacral transcutaneous electrical neural stimulation in the treatment of monosymptomatic primary enuresis. Materials and Methods: This prospective randomized clinical trial included 29 girls and 16 boys older than 6 years with primary monosymptomatic enuresis. Children were randomly divided into 2 groups consisting of controls, who were treated with behavioral therapy, and an experimental group, who were treated with behavioral therapy plus 10 sessions of parasacral transcutaneous electrical neural stimulation. Neural stimulation was performed with the electrodes placed in the sacral region (S2/S3). Sessions always followed the same pattern, with duration of 20 minutes, frequency of 10 Hz, a generated pulse of 700 ms and intensity determined by the sensitivity threshold of the child. Sessions were done 3 times weekly on alternate days. Patients in both groups were followed at 2-week intervals for the first month and then monthly for 6 consecutive months. Results: Rate of wet nights was 77% in controls and 78.3% in the experimental group at onset of treatment (p ¼ 0.82), and 49.5% and 31.2%, respectively, at the end of treatment (p ¼ 0.02). Analyzing the average rate of improvement, there was a significantly greater increase in dry nights in the group undergoing neural stimulation (61.8%) compared to controls (37.3%, p ¼ 0.0038). At the end of treatment percent improvement in children undergoing electrical stimulation had no relation to gender (p ¼ 0.391) or age (p ¼ 0.911). Conclusions: Treatment of primary monosymptomatic enuresis with 10 sessions of parasacral transcutaneous electrical neural stimulation plus behavioral therapy proved to be effective. However, no patient had complete resolution of symptoms.
Abbreviations and Acronyms CG ¼ control group EG ¼ experimental group ICCS ¼ International Children’s Continence Society PTENS ¼ parasacral transcutaneous electrical neural stimulation Accepted for publication March 26, 2013. Funded by CNPQeConselho Nacional de Pesquisa e Desenvolvimento (National Council for Research and Development) and by FAPEMIGeFundac‚~ao de Amparo a Pesquisa do Estado de Minas Gerais (Research Foundation of the State of Minas Gerais, Brazil). Study received approval of institutional ethics committee in clinical research. * Correspondence: Av. Rio Branco, 2985/sl. 605, Juiz de Fora, Minas Gerais, Brazil 36010012 (telephone: 55-32-3218-9899; FAX: 55-32-32189899; e-mail: [email protected]).
Key Words: behavior therapy, electric stimulation therapy, enuresis, transcutaneous electric nerve stimulation, urinary incontinence
ENURESIS is defined by the International Children’s Continence Society as intermittent urinary incontinence
that occurs during sleep.1,2 Although the condition has been described for thousands of years, none of the
0022-5347/13/1904-1359/0 THE JOURNAL OF UROLOGY® © 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.03.108 Vol. 190, 1359-1363, October 2013 Printed in U.S.A.
www.jurology.com
j
1359
1360
PARASACRAL ELECTRICAL NERVE STIMULATION FOR MONOSYMPTOMATIC ENURESIS
treatments currently available is sufficiently effective, perhaps due to lack of knowledge about the etiology, intervening factors, and lack of uniformity regarding concepts and definitions.3,4 Current therapeutic modes consist of medical treatment with desmopressin, imipramine or oxybutynin, and use of alarms and behavioral therapy, in which changes in the daily routine related to urination are recommended.5e8 Of the treatments described the best long-term results are achieved with alarms, with a success rate of about 77%,9 followed by desmopressin, with a complete response of approximately 37%.10 Daytime incontinence in children is usually due to overactive bladder, and treatment with PTENS is an option that can achieve excellent results.1114 A recent systematic review showed a scarcity and lack of uniformity in the parameters of PTENS in the treatment of overactive bladder.15 It is believed that PTENS has an effect on physiological reconditioning, which enables remodulation of synapses through the mechanism of neuroplasticity, hopefully achieving neural reconditioning.16 Its therapeutic effect is achieved through the recovery of cerebral activity associated with self-regulation and attenuation of activity of the cingulate gyrus, reinnervating the muscle fibers, which are partly denervated.16 To our knowledge parasacral transcutaneous eletrical neural stimulation has never been tested in the treatment of monosymptomatic enuresis. However, it has been used in nonmonosymptomatic enuresis, with improvement in number of dry nights in 63% of children and complete resolution of symptoms in 42%.17 Up to 30% of children with enuresis display nocturnal bladder overactivity.18 Due to the satisfactory results of PTENS in patients with daytime incontinence caused by overactive bladder and in those with nonmonosymptomatic enuresis,1115,17 we evaluated the efficacy of PTENS in the treatment of patients with primary monosymptomatic enuresis.
MATERIALS AND METHODS In this randomized prospective clinical trial we evaluated children older than 6 years with primary monosymptomatic enuresis. Diagnosis was made by clinical history, physical examination and voiding diary. Urinalysis was used to exclude urinary tract infection. Exclusion criteria were age younger than 6 years, presence of nonmonosymptomatic or secondary enuresis, history of treatment for enuresis within 6 months before entering the study and the presence of neurological, psychiatric or renal disease. Patients excluded from the study were followed and treated at our enuresis clinic and received other treatments for enuresis. The study was approved by the ethics committee in clinical research of our institution, and individuals responsible for the children signed an informed consent.
At the first clinical appointment a standardized clinical interview was done, consisting of questions about general health status and urinary symptoms to understand the characteristics of the enuresis. Also the parents were instructed to keep a voiding diary to help classify the enuresis as monosymptomatic or nonmonosymptomatic by evaluating frequency, bladder volumes and presence of urgency or incontinence. To quantify the number of wet nights, and to represent a start point marker for evolution and efficacy of treatment, we used a diary of wet nights in which the participants were instructed to write down the episodes of enuresis for 2 weeks before beginning treatment. Urinalysis was done to rule out urinary tract infection. Only after assessment of these data were the children randomized into 2 groups using Research Randomizer (http://www.randomizer.org). Children in the CG underwent behavioral therapy. These orientations consisted of guidance about decreasing evening liquid intake and avoiding liquids 2 hours before bedtime, curbing intake of foods and liquids containing caffeine, keeping a diary of dry nights, use of rewards for dry nights and bladder training consisting of emptying the bladder before going to bed, immediately after waking up and every 3 to 4 hours during the day, regardless of need or desire to urinate.9,19 These orientations were verbally reinforced at every clinical visit after beginning treatment (biweekly for the first month and monthly for the next 6 months) and were also printed at the back of the diary of wet nights. Children in the EG likewise underwent behavioral therapy and also underwent PTENS using a Neurodyn Evolution electrical stimulator (Ibramed, Amparo, S~ ao Paulo, Brazil). The treatment was carried out in a reserved room with the children accompanied by their parents. The child was put in the prone position and 2 electrodes were placed in the sacral region at the S2/S3 vertebral level on opposite sides of the lumbar column. The sessions lasted 20 minutes under a frequency of 10 Hz, pulse width of 700 mS and intensity determined by the sensitivity threshold of the child. A total of 10 sessions were done 3 times weekly on alternate days.12,17,20 During PTENS sessions no reinforcement of orientations was done. After completing the 10 sessions the patients were followed and reassessed every 2 weeks for the first month and monthly during the subsequent 6 months. The results were evaluated according to the ICCS standardization,1,2 in which decrease of wet nights by less than 50% signifies absence of response, reduction by 50% to 89% constitutes partial response and decrease by more than 89% indicates response. To calculate the average rate of improvement in wet nights in each group, we used the formula, improvement in % ¼ [100 e (wet days after treatment/wet days before treatment)]. Continuous variables were analyzed using the Student t test and Mann-Whitney U test. Fisher exact test was used for comparison of categorical data. Results were considered statistically significant at p <0.05.
RESULTS A total of 45 children with primary monosymptomatic enuresis were enrolled in the study,
PARASACRAL ELECTRICAL NERVE STIMULATION FOR MONOSYMPTOMATIC ENURESIS
with 18 (6 boys) in control group and 27 (10 boys) in experimental group. Mean SD age was 9.9 2.7 years (range 6.2 to 16.3) in the CG and 9.8 2.9 years (6.3 to 14.1) in the EG (p ¼ 0.92). In the CG boys had a mean age of 9.9 2.7 years and girls 9.8 2.9 years (p ¼ 0.94). In the EG boys had a mean age of 9.6 2.7 years and girls 10.0 3.2 years (p ¼ 0.70). All children completed the voiding diary and attended all scheduled clinic visits. Percentage of wet nights before treatment was 77.0% in the CG and 78.3% in the EG (p ¼ 0.82). After 6 months of followup these percentages decreased to 49.5% and 31.2%, respectively (p ¼ 0.02, fig. 1). Improvement in wet nights was 37.3% in the CG and 61.8% in the EG (p ¼ 0.0038, fig. 2). According to ICCS standardization criteria, we observed that 15% of patients in the EG responded to treatment, while 56% displayed partial response and 30% had no response. Meanwhile, in the CG these percentages were 6%, 33% and 61%, respectively. No patient in either group had complete resolution of symptoms (fig. 3). When assessed by age, in the EG the rate of wet nights before treatment was 66.7% in children older than 10 years and 79.6% in children 10 years or younger (p ¼ 0.693). After treatment these rates were 29.7% and 32.7%, respectively (p ¼ 0.911). When assessed by gender, the rate of wet nights before treatment was 88.0% in boys and 72.6% in girls (p ¼ 0.032). At the end of 6 months of followup these rates were 36.7% and 28.0%, respectively (p ¼0.391).
DISCUSSION Studies of monosymptomatic enuresis have progressed steadily. However, to date, no treatment proposed for resolution of enuresis has been observed to be completely effective, with more than a third of patients exhibiting an unsatisfactory
Figure 1. Percentage of wet nights in each group during treatment. d, days.
1361
Figure 2. Percentage of improvement in wet nights (p ¼ 0.0038)
response.17,21 Thus, we sought a new treatment modality for primary monosymptomatic enuresis, which is painless and carries no side effects. We observed that the combination of PTENS and behavioral therapy decreases the percentage of wet nights compared to behavioral therapy alone in children with monosymptomatic enuresis. This positive result can also be confirmed through analysis of average percent improvement, a variable created to better visualize the final results. According to this variable, children in the CG had an average percent improvement of 37.3%, while those undergoing PTENS and behavioral therapy had a 61.8% improvement, confirming the efficacy of this method (p ¼ 0.0038). The use of PTENS in children with enuresis was first applied by Lord^elo et al in 2010.17 Their study included only children with nonmonosymptomatic enuresis and verified that 42% of the patients were dry, 21% exhibited significant improvement of symptoms, 32% did not display any changes and 5%
Figure 3. Treatment response according to ICCS standardization.1,2 Absence of response indicates decrease of wet nights by less than 50%, partial response reduction by 50% to 89% and response decrease by more than 89%.
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PARASACRAL ELECTRICAL NERVE STIMULATION FOR MONOSYMPTOMATIC ENURESIS
had worsening of symptoms after treatment. Despite the positive results of PTENS, in addition to enuresis the children had daytime symptoms, unlike the present study, in which we evaluated only children with monosymptomatic enuresis. Improvement of daytime overactive bladder symptoms with PTENS has already been well documented, and with the resolution of overactive bladder contractions many children stop wetting the bed.12,17 By comparison, a study evaluating behavioral therapy in 23 children revealed that the number of enuretic episodes decreased by at least 1 night per week in 16 (70%), wet nights were reduced by at least 50% in 9 (39%) and full recovery was observed in 5 (22%), demonstrating the lack of sufficient effectiveness of behavioral therapy alone.22 Despite the fact that the etiology of enuresis is not well understood, it is known that nocturnal continence depends on 3 factors, namely production of nocturnal urine (nocturnal polyuria), nocturnal bladder function (nocturnal bladder overactivity), and sleep and arousal mechanisms. Therefore, any child will display enuresis if he or she produces a larger volume of urine than normal bladder capacity and/or has nocturnal detrusor overactivity associated with the inability to wake up with imminent bladder contraction and desire to void.23 These factors can be caused by an alteration of the brainstem.24 Treatment with behavioral therapy would mainly act on extrinsic factors of the body, since changes in food ingestion and habits (sleeping, voiding) would produce secondary effects on the body, normalizing bladder function through active cooperation of the child.22 By comparison, PTENS would act directly on the neurological system, resulting in physiological changes with consequent neural reconditioning. Thus, it is believed that the results observed at the end of treatment are due to the fact that the combination of the 2 therapies benefits children with enuresis by acting on different etiological factors. However, new studies must be done in this field to further confirm the efficacy of this approach. In the present study neither gender nor age influenced the effects of PTENS on improving percentage of wet nights. One would imagine that age might be a determining factor in treatment, since older children are more mature, which would enable them to follow the instructions more thoroughly
with consequent better participation and execution of the orientations. These children also show less dependency on their parents for supervision and are not affected as much if the parents cannot guide them through the training process. Complete resolution of enuresis was not found in any child in the EG after 6 months of monitoring, and 1 child (5.6%) did not display any change in symptoms, with the remainder achieving at least some improvement. The combination of PTENS and behavioral therapy in the experimental group was chosen because the recommendations used in behavioral therapy are always used when treating enuresis. It is important to add that despite the positive results found in this study, the number of sessions performed (10) might not have been enough to achieve better neuromodulation and, consequently, better results. We believe that with a greater number of PTENS sessions the results would have been better, which opens the way for new studies. Another possible flaw of the study is that children undergoing PTENS had constant contact with the researcher (3 times weekly for 10 sessions), while children treated with behavioral therapy alone had contact with a health professional only at their monthly appointment. Therefore, the clinical significance of the difference found in the outcomes between groups might be narrow, since achieving good results with behavioral therapy depends on the number of visits to professionals. To our knowledge this is the first study in which PTENS was used to treat children with monosymptomatic nocturnal enuresis. Our results, although consisting of partial response in the majority of cases, open the way for new research in this field and establish PTENS as a new therapeutic method for treating children with enuresis.
CONCLUSIONS In children with primary monosymptomatic enuresis PTENS plus behavioral therapy decreased the number of wet nights more than behavioral treatment alone. However, no patient in our series had a complete response to treatment. Therefore, new studies using PTENS for longer periods or in combination with other therapeutic modalities are needed to better understand its role in the treatment of enuresis.
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