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Functional magnetic stimulation: A new method for the treatment of girls with primary nocturnal enuresis?
Journal of Pediatric Urology (2006) 2, 415e418
Functional magnetic stimulation: A new method for the treatment of girls with primary nocturnal enuresis? ˇun Varda b,* I. But a, N. Marc a b
Department of Gynecology, Maribor University Hospital, Ljubljanska 5, 2000 Maribor, Slovenia Department of Paediatrics, Maribor University Hospital, Maribor, Slovenia
Received 24 April 2005; accepted 6 September 2005 Available online 2 November 2005
KEYWORDS Primary nocturnal enuresis; Girls; Treatment; Magnetic stimulation; Placebo
Abstract Objective: The aim of our ongoing study was to evaluate the potential clinical and urodynamic effects of functional magnetic stimulation (FMS) compared to a placebo in the treatment of girls with primary nocturnal enuresis (PNE). Patients and methods: Twenty girls with PNE (mean age 10.8 years, range 6e14 years) were included in the study and randomly divided into two groups, the active FMS group (10 girls) and the placebo group (10 girls). All girls were asked to wear Pulsegen stimulators day and night for 2 months. FMS was applied continuously at 18.5 Hz. Clinical parameters were documented and urodynamic evaluation was performed before and after FMS. Data were analyzed using non-parametric statistics. Results: The number of weekly PNE episodes decreased significantly after FMS compared to the placebo (P Z 0.007). In the active group the number of PNE episodes fell from 3.1 to 1.3 per week (P Z 0.028). Three girls from the active group were completely dry and four were significantly improved. In the FMS group a significant (P Z 0.022) increase in bladder volume at the strong desire to void was observed. Also, an increase in bladder volume at the first desire to void was observed, although this was not statistically significant (P Z 0.059). Conclusion: According to the preliminary results of our study, FMS represents a promising new method for the treatment of girls with PNE. ª 2005 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction * Corresponding author. Tel.: C386 23212110; fax: C386 23312393. E-mail address: [email protected] (N.M. Varda).
Primary nocturnal enuresis (PNE) is considered to be a benign, but very common and unpleasant, disorder in healthy children. It is defined as
1477-5131/$30 ª 2005 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2005.09.006
416 monosymptomatic bedwetting in children of at least 5 years of age who have never been dry at night for an uninterrupted period of at least 6 months [1]. A great variety of treatments have been used over the years for bedwetting children, e.g. behavioral therapy (motivation therapy, bladder training, alarm systems) [2,3], pharmacotherapy (desmopressin, imipramine, anticholinergics) [4e6] and anal maximal electric stimulation [7]. None of these treatments has proved to be completely successful, probably because nocturnal enuresis is accepted to be a multifactorial condition, although the exact pathophysiology has yet to be defined [8]. Among possible pathogenic factors in PNE, detrusor instability and a reduction in functional bladder capacity have been suggested by some authors, particularly in those patients with refractory symptoms and treatment failure [9e11]. In recent years functional magnetic stimulation (FMS) has been proposed as an alternative to electrical stimulation for the conservative treatment of bladder overactivity [12,13]. At present, treatment results are available only in women. There are no data available on the potential efficacy of this method for the treatment of PNE in girls. The aim of our pilot study was to establish whether FMS is also effective in the treatment of girls with PNE.
Patients and methods Twenty girls with documented PNE, diagnosed in our Pediatric Nephrology Unit, were included in this randomized, placebo-controlled and doubleblind pilot study. To ensure that the girls had monosymptomatic PNE a detailed voiding history was obtained for each case, with even minor signs of voiding dysfunction being sought [2]. Definitions and recommendations, presented at the first International Children’s Continence Society meeting, were used [1]. The study was approved by the local ethics committee and written informed consent was obtained from each parent. At least 3 months prior to entry into the study all the girls had unsuccessfully undergone at least one mode of treatment. Physical examination, urinalysis, and pre- and post-voiding ultrasound of the urinary tract were normal. In all girls pre-treatment urodynamic studies were performed in the presence of their parents, according to the methods described elsewhere [14]. Active or placebo Pulsegen devices (Fig. 1), identical in appearance and labeled with serial
I. But, N.M. Varda
Figure 1
The Pulsegen device.
numbers, were randomly assigned to the girls as they entered the study. The girls were instructed to wear the devices continuously for 2 months, in specially designed underpants, and to keep a detailed written voiding diary, including voiding times, evidence of each dry night, possible treatment side effects and the time when the device was worn. The active device generates a pulsating electromagnetic field of low frequencies. It is in a plastic case and designed for home use (dimensions: 45 mm long, 30 mm wide and 10 mm thick; weight without battery, 9.5 g). The Pulsegen stimulator is powered by a 3 V battery, allowing 8 weeks of continuous FMS (pulse frequency of 18.5 Hz, intensity of B Z 10 mT at a distance of 7.5 cm from the case). The device is turned on by pressing a small switch located on its front, with a green light blinking on the front while the device is active. Shortly after 2 months of continuous treatment, urodynamic studies were repeated and the clinical effect of treatment assessed by the girls and their parents. The girls were considered to have a significant response to the treatment when there was a 50% or greater decrease in the number of wet nights. After termination of treatment all the girls were asked to continue the detailed voiding diary. The study results were analyzed by the statistician, the only person aware of the list of active
Primary nocturnal enuresis: New treatment and placebo devices, using the computer program Statistica 6.0 (Stat Soft Inc. 2001, USA) and basic non-parametric statistical methods to test the intragroup and intergroup differences (Wilcoxon matched pairs test, ManneWhitney U-test). P ! 0.05 was considered statistically significant.
417 first desire to void also increased, although this was not statistically significant (P Z 0.059) (Table 1). Bladder capacity in the FMS group increased by 12% (P Z 0.11), while in the placebo group it was practically unchanged (Table 1). No discomfort or adverse effects were reported by the girls or their parents, and none had their treatment discontinued.
Results The average age of 20 girls with PNE was 10.8 years (6e14 years) and the average number of nocturnal enuretic episodes was 3.7 per week (1e7 wet nights per week). Ten girls were treated with active devices and the remainder with placebo devices. No significant differences were found between the two groups in terms of age, enuretic episodes and urodynamic parameters (P O 0.05). Detrusor overactivity was found in 11 girls, seven from the active group and four from the placebo group. The average maximal bladder capacity before treatment was 244.6 ml in the active group and 215.9 ml in the placebo group. Compared to the placebo, a significant improvement in nocturnal enuretic episodes was observed after FMS (P Z 0.007), with the number of posttreatment nocturnal enuretic episodes per week averaging 1.3 for the active group and 3.0 for the placebo group (Table 1). In girls from the active group the average number of enuretic episodes fell from 3.1 to 1.3 per week (P Z 0.028). In seven out of 10 girls from the active group significant improvement was observed compared to four out of 10 girls from the placebo group (P Z 0.18). After the period of stimulation no PNE episodes were observed in three girls from the FMS group, and in one from the placebo group. Bladder overactivity disappeared in five girls from the active group and in two girls from the placebo group. Compared to pre-treatment levels bladder volume at the maximal desire to void increased significantly after stimulation in girls from the active group (P Z 0.022). Bladder volume at the
Discussion This study was designed to determine the efficacy and safety of FMS in the treatment of girls with PNE. It seems that FMS induces inhibitory effects on detrusor overactivity in a similar manner to electrical stimulation [12], and bladder overactivity is among many factors thought to be associated with PNE [9e11]. Hence, we hypothesized that FMS might be effective in the treatment of PNE in children. We are not aware of any previous study on the use of FMS in children, but electrical stimulation has been used in children with micturition problems. In a review carried out by Bower and Yeung [15], six studies on electromodulation in children with non-neurogenic bladder dysfunction showed clear benefits in clinical and urodynamic parameters. In the study by Trsˇinar and Kralj [7], 75% of the stimulated patients showed at least a 50% improvement, whereas no change was seen in 86% of the control group. In the present study 20 girls with PNE were included in whom a detailed history taken verified that they had no additional daytime urinary symptoms to suggest underlying voiding dysfunction. Ten girls received FMS, the remainder placebo. Both groups did not differ significantly in terms of pre-treatment urodynamic parameters or clinical characteristics. Post-treatment, a significant improvement in nocturnal enuretic episodes was observed only in the active group. The average number of weekly nocturnal episodes fell from 3.1 to 1.3. After the treatment seven girls out of 10
Table 1 Clinical and urodynamic parameters in girls with primary nocturnal enuresis (PNE) before and after treatment with functional magnetic stimulation (FMS) Active device BV at first desire to void (ml) BV at strong desire to void (ml) Bladder capacity (ml) PNE/week (number) BV, bladder volume.
Placebo device
Before FMS
After FMS
P
Before
After
P
106.3 215.3 244.6 3.1
140.5 264.3 273.1 1.3
0.059 0.022 0.11 0.028
94.4 167.4 215.9 3.7
106.7 180.4 210.0 3.0
0.35 0.17 0.74 0.068
418 were significantly improved, which correlates well with response rates reported for other treatment protocols using desmopressin or alarm devices [3,4]. Before treatment, detrusor instability was found in 11 girls (55%). This is in agreement with the report by Medel et al. [16], in which bladder overactivity was found in 49% of children with bedwetting as the only symptom. According to Yeung et al. [10] many children without daytime symptoms suffer from bladder overactivity or a reduced bladder capacity during the night. Therefore, it is possible that a higher prevalence of detrusor overactivity would be observed during a nighttime study. Since detrusor overactivity implies that the detrusor is not perfectly relaxed between voidings, the reservoir capacity of the overactive bladder will be smaller than in a bladder with a normally relaxed detrusor. In our study the average bladder capacity at the maximal desire to void was quite small before FMS (Table 1); however, it increased significantly after FMS verifying the clinical observation that the treatment was effective. After FMS the maximum cystometric capacity also increased, but this change in bladder volume was not significant. FMS has been reported to be safe, non-invasive, painless and easy to use, and without adverse effects [12], making it very suitable for use in children. These observations were confirmed in our study. As our sample size was small, a future study involving a larger number of girls with PNE is recommended. FMS should also be tested in boys with PNE, as there might be differences in the pathogenesis of PNE between the sexes [10]. In conclusion, our study, which is considered a pilot investigation of the device, demonstrated that FMS appears to be a promising new method for the treatment of girls with PNE. The results need to be confirmed in a larger, randomized, placebocontrolled study. If the effectiveness of the method is proven, its place in the management strategy (first-line or second-line therapy) should be defined. In addition, further studies are needed to evaluate the long-term efficacy of this potential treatment.
I. But, N.M. Varda
References [1] Nørgaard JP, van Gool JD, Hja ¨lmas K, et al. Standardization and definitions in lower urinary tract dysfunction in children. Br J Urol 1998;81(Suppl. 3):1e16. [2] Pennesi M, Pitter M, Bordungo A, et al. Behavioral therapy for primary nocturnal enuresis. J Urol 2004;171:408e10. [3] Butler RJ, Robinson JC. Alarm treatment for childhood nocturnal enuresis. Scand J Urol Nephrol 2002;36:268e72. [4] Tullus K, Bergstro ¨m R, Fosdal I, et al. Efficacy and safety during long-term treatment of primary monosymptomatic nocturnal enuresis with desmopressin. Acta Paediatr 1999;88:1274e8. [5] Cendron M, Klauber G. Combination therapy in the treatment of persistent nocturnal enuresis. Br J Urol 1998; 81(Suppl. 3):26e8. [6] La ¨ckgren G, Hja ¨lmas K, van Gool J, et al. Nocturnal enuresis: a suggestion for a European treatment strategy. Acta Paediatr 1999;88:679e90. [7] Trsˇinar B, Kralj B. Maximal electrical stimulation in children with unstable bladder and nocturnal enuresis and/or daytime incontinence: a controlled study. Neurourol Urodyn 1996;15:133e42. [8] Evans J, Shenoy M. Disorders of micturition. In: Webb N, Postlethwaite R, editors. Clinical paediatric nephrology. 3rd ed. New York: Oxford University Press; 2003. p. 163e78. [9] Nørgaard JP, Djurhuus JC, Watanabe H, et al. Experience and current status of research into the pathophysiology of nocturnal enuresis. Br J Urol 1997;79:825e35. [10] Yeung CK, Sit FKY, To LKC, et al. Reduction in nocturnal functional bladder capacity is a common factor in the pathogenesis of refractory nocturnal enuresis. BJU Int 2002;90:302e7. [11] Yeung CK. Nocturnal enuresis (bedwetting). Curr Opin Urol 2003;13:337e43. [12] Yamanishi T, Sakakibara R, Uchiyama T, et al. Comparative study of the effects of magnetic versus electrical stimulation on inhibition of detrusor overactivity. Urology 2000; 56:777e81. [13] But I. Conservative treatment of female urinary incontinence with functional magnetic stimulation. Urology 2003;61:558e61. [14] Hoebeke P, Vande Walle J, Everaert K, et al. Assessment of lower urinary tract dysfunction in children with non-neuropathic bladder sphincter dysfunction. Eur Urol 1999;35: 57e9. [15] Bower WF, Yeung CK. A review of non-invasive electro-neuromodulation as an intervention for non-neurogenic bladder dysfunction in children. Neurourol Urodyn 2004;23: 63e7. [16] Medel R, Ruarte AC, Castera R, et al. Primary enuresis: a urodynamic evaluation. Br J Urol 1998;81(Suppl. 3): 50e2.
Functional magnetic stimulation: A new method for the treatment of girls with primary nocturnal enuresis? ˇun Varda b,* I. But a, N. Marc a b
Department of Gynecology, Maribor University Hospital, Ljubljanska 5, 2000 Maribor, Slovenia Department of Paediatrics, Maribor University Hospital, Maribor, Slovenia
Received 24 April 2005; accepted 6 September 2005 Available online 2 November 2005
KEYWORDS Primary nocturnal enuresis; Girls; Treatment; Magnetic stimulation; Placebo
Abstract Objective: The aim of our ongoing study was to evaluate the potential clinical and urodynamic effects of functional magnetic stimulation (FMS) compared to a placebo in the treatment of girls with primary nocturnal enuresis (PNE). Patients and methods: Twenty girls with PNE (mean age 10.8 years, range 6e14 years) were included in the study and randomly divided into two groups, the active FMS group (10 girls) and the placebo group (10 girls). All girls were asked to wear Pulsegen stimulators day and night for 2 months. FMS was applied continuously at 18.5 Hz. Clinical parameters were documented and urodynamic evaluation was performed before and after FMS. Data were analyzed using non-parametric statistics. Results: The number of weekly PNE episodes decreased significantly after FMS compared to the placebo (P Z 0.007). In the active group the number of PNE episodes fell from 3.1 to 1.3 per week (P Z 0.028). Three girls from the active group were completely dry and four were significantly improved. In the FMS group a significant (P Z 0.022) increase in bladder volume at the strong desire to void was observed. Also, an increase in bladder volume at the first desire to void was observed, although this was not statistically significant (P Z 0.059). Conclusion: According to the preliminary results of our study, FMS represents a promising new method for the treatment of girls with PNE. ª 2005 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction * Corresponding author. Tel.: C386 23212110; fax: C386 23312393. E-mail address: [email protected] (N.M. Varda).
Primary nocturnal enuresis (PNE) is considered to be a benign, but very common and unpleasant, disorder in healthy children. It is defined as
1477-5131/$30 ª 2005 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2005.09.006
416 monosymptomatic bedwetting in children of at least 5 years of age who have never been dry at night for an uninterrupted period of at least 6 months [1]. A great variety of treatments have been used over the years for bedwetting children, e.g. behavioral therapy (motivation therapy, bladder training, alarm systems) [2,3], pharmacotherapy (desmopressin, imipramine, anticholinergics) [4e6] and anal maximal electric stimulation [7]. None of these treatments has proved to be completely successful, probably because nocturnal enuresis is accepted to be a multifactorial condition, although the exact pathophysiology has yet to be defined [8]. Among possible pathogenic factors in PNE, detrusor instability and a reduction in functional bladder capacity have been suggested by some authors, particularly in those patients with refractory symptoms and treatment failure [9e11]. In recent years functional magnetic stimulation (FMS) has been proposed as an alternative to electrical stimulation for the conservative treatment of bladder overactivity [12,13]. At present, treatment results are available only in women. There are no data available on the potential efficacy of this method for the treatment of PNE in girls. The aim of our pilot study was to establish whether FMS is also effective in the treatment of girls with PNE.
Patients and methods Twenty girls with documented PNE, diagnosed in our Pediatric Nephrology Unit, were included in this randomized, placebo-controlled and doubleblind pilot study. To ensure that the girls had monosymptomatic PNE a detailed voiding history was obtained for each case, with even minor signs of voiding dysfunction being sought [2]. Definitions and recommendations, presented at the first International Children’s Continence Society meeting, were used [1]. The study was approved by the local ethics committee and written informed consent was obtained from each parent. At least 3 months prior to entry into the study all the girls had unsuccessfully undergone at least one mode of treatment. Physical examination, urinalysis, and pre- and post-voiding ultrasound of the urinary tract were normal. In all girls pre-treatment urodynamic studies were performed in the presence of their parents, according to the methods described elsewhere [14]. Active or placebo Pulsegen devices (Fig. 1), identical in appearance and labeled with serial
I. But, N.M. Varda
Figure 1
The Pulsegen device.
numbers, were randomly assigned to the girls as they entered the study. The girls were instructed to wear the devices continuously for 2 months, in specially designed underpants, and to keep a detailed written voiding diary, including voiding times, evidence of each dry night, possible treatment side effects and the time when the device was worn. The active device generates a pulsating electromagnetic field of low frequencies. It is in a plastic case and designed for home use (dimensions: 45 mm long, 30 mm wide and 10 mm thick; weight without battery, 9.5 g). The Pulsegen stimulator is powered by a 3 V battery, allowing 8 weeks of continuous FMS (pulse frequency of 18.5 Hz, intensity of B Z 10 mT at a distance of 7.5 cm from the case). The device is turned on by pressing a small switch located on its front, with a green light blinking on the front while the device is active. Shortly after 2 months of continuous treatment, urodynamic studies were repeated and the clinical effect of treatment assessed by the girls and their parents. The girls were considered to have a significant response to the treatment when there was a 50% or greater decrease in the number of wet nights. After termination of treatment all the girls were asked to continue the detailed voiding diary. The study results were analyzed by the statistician, the only person aware of the list of active
Primary nocturnal enuresis: New treatment and placebo devices, using the computer program Statistica 6.0 (Stat Soft Inc. 2001, USA) and basic non-parametric statistical methods to test the intragroup and intergroup differences (Wilcoxon matched pairs test, ManneWhitney U-test). P ! 0.05 was considered statistically significant.
417 first desire to void also increased, although this was not statistically significant (P Z 0.059) (Table 1). Bladder capacity in the FMS group increased by 12% (P Z 0.11), while in the placebo group it was practically unchanged (Table 1). No discomfort or adverse effects were reported by the girls or their parents, and none had their treatment discontinued.
Results The average age of 20 girls with PNE was 10.8 years (6e14 years) and the average number of nocturnal enuretic episodes was 3.7 per week (1e7 wet nights per week). Ten girls were treated with active devices and the remainder with placebo devices. No significant differences were found between the two groups in terms of age, enuretic episodes and urodynamic parameters (P O 0.05). Detrusor overactivity was found in 11 girls, seven from the active group and four from the placebo group. The average maximal bladder capacity before treatment was 244.6 ml in the active group and 215.9 ml in the placebo group. Compared to the placebo, a significant improvement in nocturnal enuretic episodes was observed after FMS (P Z 0.007), with the number of posttreatment nocturnal enuretic episodes per week averaging 1.3 for the active group and 3.0 for the placebo group (Table 1). In girls from the active group the average number of enuretic episodes fell from 3.1 to 1.3 per week (P Z 0.028). In seven out of 10 girls from the active group significant improvement was observed compared to four out of 10 girls from the placebo group (P Z 0.18). After the period of stimulation no PNE episodes were observed in three girls from the FMS group, and in one from the placebo group. Bladder overactivity disappeared in five girls from the active group and in two girls from the placebo group. Compared to pre-treatment levels bladder volume at the maximal desire to void increased significantly after stimulation in girls from the active group (P Z 0.022). Bladder volume at the
Discussion This study was designed to determine the efficacy and safety of FMS in the treatment of girls with PNE. It seems that FMS induces inhibitory effects on detrusor overactivity in a similar manner to electrical stimulation [12], and bladder overactivity is among many factors thought to be associated with PNE [9e11]. Hence, we hypothesized that FMS might be effective in the treatment of PNE in children. We are not aware of any previous study on the use of FMS in children, but electrical stimulation has been used in children with micturition problems. In a review carried out by Bower and Yeung [15], six studies on electromodulation in children with non-neurogenic bladder dysfunction showed clear benefits in clinical and urodynamic parameters. In the study by Trsˇinar and Kralj [7], 75% of the stimulated patients showed at least a 50% improvement, whereas no change was seen in 86% of the control group. In the present study 20 girls with PNE were included in whom a detailed history taken verified that they had no additional daytime urinary symptoms to suggest underlying voiding dysfunction. Ten girls received FMS, the remainder placebo. Both groups did not differ significantly in terms of pre-treatment urodynamic parameters or clinical characteristics. Post-treatment, a significant improvement in nocturnal enuretic episodes was observed only in the active group. The average number of weekly nocturnal episodes fell from 3.1 to 1.3. After the treatment seven girls out of 10
Table 1 Clinical and urodynamic parameters in girls with primary nocturnal enuresis (PNE) before and after treatment with functional magnetic stimulation (FMS) Active device BV at first desire to void (ml) BV at strong desire to void (ml) Bladder capacity (ml) PNE/week (number) BV, bladder volume.
Placebo device
Before FMS
After FMS
P
Before
After
P
106.3 215.3 244.6 3.1
140.5 264.3 273.1 1.3
0.059 0.022 0.11 0.028
94.4 167.4 215.9 3.7
106.7 180.4 210.0 3.0
0.35 0.17 0.74 0.068
418 were significantly improved, which correlates well with response rates reported for other treatment protocols using desmopressin or alarm devices [3,4]. Before treatment, detrusor instability was found in 11 girls (55%). This is in agreement with the report by Medel et al. [16], in which bladder overactivity was found in 49% of children with bedwetting as the only symptom. According to Yeung et al. [10] many children without daytime symptoms suffer from bladder overactivity or a reduced bladder capacity during the night. Therefore, it is possible that a higher prevalence of detrusor overactivity would be observed during a nighttime study. Since detrusor overactivity implies that the detrusor is not perfectly relaxed between voidings, the reservoir capacity of the overactive bladder will be smaller than in a bladder with a normally relaxed detrusor. In our study the average bladder capacity at the maximal desire to void was quite small before FMS (Table 1); however, it increased significantly after FMS verifying the clinical observation that the treatment was effective. After FMS the maximum cystometric capacity also increased, but this change in bladder volume was not significant. FMS has been reported to be safe, non-invasive, painless and easy to use, and without adverse effects [12], making it very suitable for use in children. These observations were confirmed in our study. As our sample size was small, a future study involving a larger number of girls with PNE is recommended. FMS should also be tested in boys with PNE, as there might be differences in the pathogenesis of PNE between the sexes [10]. In conclusion, our study, which is considered a pilot investigation of the device, demonstrated that FMS appears to be a promising new method for the treatment of girls with PNE. The results need to be confirmed in a larger, randomized, placebocontrolled study. If the effectiveness of the method is proven, its place in the management strategy (first-line or second-line therapy) should be defined. In addition, further studies are needed to evaluate the long-term efficacy of this potential treatment.
I. But, N.M. Varda
References [1] Nørgaard JP, van Gool JD, Hja ¨lmas K, et al. Standardization and definitions in lower urinary tract dysfunction in children. Br J Urol 1998;81(Suppl. 3):1e16. [2] Pennesi M, Pitter M, Bordungo A, et al. Behavioral therapy for primary nocturnal enuresis. J Urol 2004;171:408e10. [3] Butler RJ, Robinson JC. Alarm treatment for childhood nocturnal enuresis. Scand J Urol Nephrol 2002;36:268e72. [4] Tullus K, Bergstro ¨m R, Fosdal I, et al. Efficacy and safety during long-term treatment of primary monosymptomatic nocturnal enuresis with desmopressin. Acta Paediatr 1999;88:1274e8. [5] Cendron M, Klauber G. Combination therapy in the treatment of persistent nocturnal enuresis. Br J Urol 1998; 81(Suppl. 3):26e8. [6] La ¨ckgren G, Hja ¨lmas K, van Gool J, et al. Nocturnal enuresis: a suggestion for a European treatment strategy. Acta Paediatr 1999;88:679e90. [7] Trsˇinar B, Kralj B. Maximal electrical stimulation in children with unstable bladder and nocturnal enuresis and/or daytime incontinence: a controlled study. Neurourol Urodyn 1996;15:133e42. [8] Evans J, Shenoy M. Disorders of micturition. In: Webb N, Postlethwaite R, editors. Clinical paediatric nephrology. 3rd ed. New York: Oxford University Press; 2003. p. 163e78. [9] Nørgaard JP, Djurhuus JC, Watanabe H, et al. Experience and current status of research into the pathophysiology of nocturnal enuresis. Br J Urol 1997;79:825e35. [10] Yeung CK, Sit FKY, To LKC, et al. Reduction in nocturnal functional bladder capacity is a common factor in the pathogenesis of refractory nocturnal enuresis. BJU Int 2002;90:302e7. [11] Yeung CK. Nocturnal enuresis (bedwetting). Curr Opin Urol 2003;13:337e43. [12] Yamanishi T, Sakakibara R, Uchiyama T, et al. Comparative study of the effects of magnetic versus electrical stimulation on inhibition of detrusor overactivity. Urology 2000; 56:777e81. [13] But I. Conservative treatment of female urinary incontinence with functional magnetic stimulation. Urology 2003;61:558e61. [14] Hoebeke P, Vande Walle J, Everaert K, et al. Assessment of lower urinary tract dysfunction in children with non-neuropathic bladder sphincter dysfunction. Eur Urol 1999;35: 57e9. [15] Bower WF, Yeung CK. A review of non-invasive electro-neuromodulation as an intervention for non-neurogenic bladder dysfunction in children. Neurourol Urodyn 2004;23: 63e7. [16] Medel R, Ruarte AC, Castera R, et al. Primary enuresis: a urodynamic evaluation. Br J Urol 1998;81(Suppl. 3): 50e2.