Pediatr Surg Int (2014) 30:663–668 DOI 10.1007/s00383-014-3503-0
ORIGINAL ARTICLE
Functional electrical stimulation for management of urinary incontinence in children with myelomeningocele: a randomized trial Abdol-Mohammad Kajbafzadeh • Lida Sharifi-Rad Seyedeh Sanam Ladi Seyedian • Ahmad Masoumi
•
Accepted: 2 April 2014 / Published online: 17 April 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose To report the efficacy of transcutaneous functional electrical stimulation (FES) in children with refractory neuropathic urinary incontinence secondary to myelomeningocele (MMC). Methods Thirty children with history of MMC (12 girls and 18 boys, mean age 6.7 ± 3.6 years) with refractory urinary incontinence were enrolled in this study. They were randomly allocated to treatment (FES, 15 children) and control (sham stimulation, 15 children) groups. All patients underwent urodynamic study (UDS) before and 6 months after FES considering detrusor leak point pressure (DLPP), mean maximal detrusor pressure, and mean maximal bladder capacity. Daily incontinence score, frequency of pad changing, and enuresis were also assessed before and 6 months after treatment. A 15-course FES was performed for 15 min and 3 times per week. Children were followed for at least 6 months. Results Of UDS variables, DLPP increased significantly from 32 ± 10.7 cmH2O before treatment to 55.6 ± 24.9 cmH2O in treatment group after 6 months (P \ 0.03). Daily incontinence score (range 0–3) improved significantly in treatment group from 2.7 ± 0.4 before
treatment to 1.3 ± 0.9 after treatment compared with sham stimulation group (P \ 0.02). Conclusion This type of electrical stimulation is a safe, noninvasive, and effective modality to improve urinary incontinence in myelomeningocele children and can be used at home. Keywords Functional electrical stimulation Myelomeningocele Neuropathic bladder Urinary incontinence Abbreviations FES Functional electrical stimulation MMC Myelomeningocele UDS Urodynamic study DLPP Detrusor leak point pressure MMBC Mean maximal bladder capacity MMDP Mean maximal detrusor pressure ICCS International children’s continent society
Introduction
A.-M. Kajbafzadeh (&) S. S. Ladi Seyedian A. Masoumi Pediatric Urology Research Center and Department of Pediatric Urology, Children’s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, 62 Qarib St, Keshavarz Blvd, 1419733151 Tehran, Iran (IRI) e-mail: [email protected] L. Sharifi-Rad Department of Physical Therapy, Children’s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran (IRI)
Myelomeningocele (MMC) is the most common form of spina bifida. Live born infants with MMC have a mortality rate of about 10 % [1]. The survivors will suffer from numerous complications including different types of neurological deficits, paralysis, and bladder and bowel dysfunction. This is important to note that renal failure is the leading cause of death after the first few years of life; therefore, early urologic management of these patients is essential [2]. Medical therapy with anticholinergic drugs either alone or with clean intermittent catheterization (CIC)
123
664
is the first line of treatment in MMC patients. This approach is the most effective treatment for these children; however, different aggressive managements are recommended for patients who are not responding well to supportive therapy. Electrical stimulation has been introduced as an alternative treatment modality for a number of urologic complaints since 1963 [3]. It is hypothesized that electrical stimulation causes action potential in the afferent fibers of pudendal nerve in which lead to efferent outflow causing contraction of the striated pelvic floor muscles [4]. Moreover, detrusor inhibitory reflex might be activated by electrical stimulation. Functional electrical stimulation (FES) is a type of electrical current which uses for the excitable tissue in order to improve function that is lost in neurologically damaged. Our prior study looked at the use of transcutaneous FES in the treatment of urinary incontinence in children with MMC [5]. We reported a decrease in urinary incontinence score after FES therapy. Most of the results proved to be long term, however; there were patients who needed to repeat FES therapy. As this method was introduced for the first time in our previous study, the aim of this study was to reassure the effects of FES therapy on management of urinary incontinence in MMC children by comparing the results with the sham stimulation group.
Pediatr Surg Int (2014) 30:663–668
Patients Twelve girls and eighteen boys with MMC between 3 and 13 years of age, with moderate-to-severe urinary incontinence (score 2 and 3) resistant to conventional treatment (demonstrating adverse effects or unsatisfactory success rate), requiring CIC every 3–4 h and use of pads were registered for this single-center study. All patients were on CIC and anticholinergics. Moreover, they were on maximum medical therapy without acceptable response to medication. Botox or any other therapy had not been tried for all patients previously. In addition, patients who had constipation had been managed with diet and mild laxatives. All patients underwent a detailed medical history and physical examination, urinalysis, renal ultrasonography, and urodynamic study (UDS). Mean maximal bladder capacity (MMBC), mean maximal detrusor pressure (MMDP), and mean detrusor leak point pressure (DLPP) were recorded according to International Children’s Continence Society (ICCS) recommendations [7]. The 30 patients eligible for the study were randomly allocated to treatment (FES, 15 children) and control (sham stimulation, 15 children) groups. Patients were unaware of the group assignment and so was the urodynamic nurse practitioner. They were followed up for the next 6 months.
Urodynamic measurement Materials and methods We included 30 MMC children who were referred to our outpatient pediatric urology clinic at Children’s Hospital Medical Center, Tehran University of Medical Sciences, in this prospective and randomized (balance block randomization) trial study between August 2009 and September 2012. Children with additional neurologic abnormalities other than MMC sequelae and children with underlying medical conditions (metabolic diseases, anorectal and urogenital malformations, previous urogenital surgery) were excluded from the study. All parents were instructed to fill out a voiding diary with providing data about the episodes of enuresis (the number of nights that the child involuntarily micturates during sleep in a 1-week period), frequency of pad changing (the number of wetting episodes between 2 consecutive CICs). The daily incontinence score was recorded on a 0–3 scale, as described by Schurch et al. [6]: score 0, completely dry; 1, wet once a day, usually at night (mild); 2, wet for \50 % of the time between CIC (moderate); and 3, wet for [50 % of the time between CIC (severe). A decrement of 2 or more degrees in the daytime incontinence score was considered as ‘‘improvement.’’
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The UDS evaluations (F.M. Wiest Medizintechnik, GmbH, Unterhaching, Germany) were complied with regard to ICCS recommendations in all patients in supine position. A double-lumen catheter and rectal balloon catheter were used to measure the intravesical and intraabdominal pressure simultaneously. Patch electrodes in the perineal area recorded EMG. Special attention was given to DLPP, MMDP, and MMBC. The same protocol was used for the UDSs performed 6 months after FES courses. Patients were asked to discontinue their anticholinergic medication intake at least 7 days prior to both UDS sessions. Success was defined as any significant reduction in each of these UDS parameters compared to our sham stimulation group. In addition, subjective success was assessed using a voiding diary and the results compared between both groups.
Functional electrical stimulation Following pretreatment UDS, anticholinergic medication and CIC were continued. FES was applied for a total of 15 sessions, 15 min each and three times per week. The same electrical stimulation device (Model ISOTERAP 786 DS?,
Pediatr Surg Int (2014) 30:663–668
665 Table 1 Demographic and clinical characteristics of children in the treatment and control groups
Age (years)
Case15
Control15
5.9
7.5
Gender (%) Female
7 (46 %)
5 (34 %)
Male
8 (54 %)
10 (66 %)
5 (34 %)
4 (26 %)
7 (46 %) 3 (20 %)
6 (40 %) 5 (34 %)
4 (26 %)
3 (20 %)
2 (13 %)
3 (20 %)
MMC level no. (%) Sacral Lower lumbar Upper lumbar Movement disorder no. (%) Paraplegia Proximal weakness
Fig. 1 Applying of positive and negative electrodes for FES
Distal weakness
6 (40 %)
7 (46 %)
Normal
3 (20 %)
2 (13 %)
6 (40 %)
7 (46 %)
Hip disorder
4 (26 %)
2 (13 %)
Hydrocephalus
2 (13 %)
4 (26 %)
History of concurrent disability no. (%) Club foot
Tavanbakhsh Novin Tehran, Iran) was used for all patients. The FES delivered a 40 Hz frequency (to cover both the irritative and obstructive symptoms and stimulate striated muscle fibers and urethral sphincter in pelvic floor), a duration of 250 ls, with hold and rest time of 2 s with adjustable amplitude (range 20–65 mA).The FES was applied according to the method of our previous study by a physiotherapist [5]. Two rectangular self-adhesive (2.5 9 3.5 cm) electrodes were applied in which positive electrode was placed on the skin above the pubic symphysis, and the negative one was placed on the skin under urethra (in female over the labia major and in male under the scrotum) (Fig 1). The intensity was increased until the child reported a strong but comfortable level of muscle contractions in the treatment group. In smaller children, an intensity setting of \30 mA was applied. Maximum current intensity was below the pain threshold and well tolerated by the children in the treatment group. All patients in the treatment group received FES for 15 courses, 15 min each and 3 times per week. Patients in control group also underwent an identical setting of procedure without increasing the intensity and conveying the FES therapy for 15 courses, 15 min each session and 3 times per week. After completion of FES courses, patients in both groups were followed for next 6 months.
Statistical analysis Statistical analysis was performed with statistical package of social science software version 17 (SPSS Inc., Chicago, IL, USA). Chi-square test or Wilcoxon signed-rank test
MMC myelomeningocele
was executed for nonparametric statistical comparisons before and after the treatment in both cohorts. Mann– Whitney U test and Student’s t test were performed wherever applicable to compare the values between two groups. Data are expressed as mean ± SD, and P \ 0.05 was considered statically significant.
Results A total of 30 MMC children with mean age of 6.7 ± 3.6 years were enrolled in this study. The treatment group comprised of 8 boys and 7 girls with mean age of 5.9 ± 3.5 years and control group included 10 boys and 5 girls with mean age of 7.4 ± 3.6 years. Both treatment and control groups were similar with regard to age, gender, and pre-intervention voiding diary (P [ 0.05). All patients in both groups completed the study protocol until follow-up. The baseline demographic data of treatment and control groups are shown in Table 1. Daily incontinence score (range 0–3) improved significantly in treatment group from 2.7 ± 0.4 before treatment to 1.3 ± 0.9 after treatment compared with sham stimulation group (P \ 0.02, Table 2). Comparing the two groups, 3 of 15 patients in treatment group became completely dry between two consecutive CICs and daily incontinence score was improved from 3 to 1 in four patients in treatment group at follow-up. Two of 15 patients in treatment group and 8/15
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Table 2 Urodynamic and voiding diary parameters of children before and after 6 months following FES (treatment) and sham stimulation (control) Variables
Groups
Before FES therapy
6 mon. after FES therapy
Pc value
Detrusor leak point pressure (cmH2O)
Treatment
32 ± 10.7
55.6 ± 24.9
0.000
control
33.5 ± 9
37 ± 11
0.261
Pab
0.682
0.03
Mean maximal bladder capacity
Treatment
183 ± 91
260 ± 87
0.01
control
193 ± 78
204 ± 87
0.433
(ml)
Pab
0.765
0.110
Mean maximal detrusor pressure (cmH2O)
Treatment
59 ± 31
38 ± 16
0.004
control
44 ± 22
50 ± 27
0.316
Pab
0.145
0.158
Mean detrusor compliance (ml/cmH2O)
Treatment control
6.7 ± 4.9 8.3 ± 4.7
12.4 ± 5.7 10.2 ± 5.2
Pab
0.386
0.286
Daily incontinence score (range 0–3)
Treatment
2.7 ± 0.4
1.3 ± 0.9
0.000
control
2.5 ± 0.5
2 ± 0.6
0.105
P
ab
0.002 0.018
0.438
0.02
Frequency of pad changing (times/day)
Treatment
5.2 ± 1.6
2.4 ± 1.4
0.000
control
4.3 ± 1.7
3.5 ± 1.6
0.005
Pab
0.169
0.03
Enuresis (night/week)
Treatment
4.1 ± 2.5
2.7 ± 0.9
0.02
control
5.6 ± 2.7
4.5 ± 3.3
0.116
Pab
0.191
0.205
Bold numbers show significant P values a
Mann–Whitney U test, bStudent’s t test, cWilcoxon signed-rank test
patients in control group remained unchanged for their daily incontinence score (P \ 0.02). Frequency of pad changing was significantly decreased in treatment group in comparison with control group. This characteristic decreased from (5.2 ± 1.6 times/day versus 4.3 ± 1.7 times/day) before FES therapy to (2.4 ± 1.4 times/day versus 3.5 ± 1.6 times/day) after FES therapy at follow-up (P \ 0.03). Of UDS parameters, DLPP increased from 32 ± 10.7 cmH2O before treatment to 55.6 ± 24.9 cmH2O after 6 months of FES therapy (P \ 0.03). MMDP decreased in treatment group compared with controls (38 ± 16 versus 50 ± 27 cmH2O), but this finding was not significant. The details of voiding diary and UDS parameters before and after treatment are shown in Table 2. Moreover, children and their parents did not report any significant adverse effects after the treatment.
Discussion Myelomeningocele is one of the most serious congenital defects with an incidence of 1.6 per 1,000 live births in Iran
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[8]. This defect is caused by the inability of neural tube to close during early gestational period and usually presents by lower limb paresis and bowel and bladder dysfunction. One of the most serious complications of MMC is renal damage due to the poor bladder compliance and detrusor overactivity [9]. Thus, early treatment of bladder dysfunction is crucial to avoid these sequelae. Currently most urologists treat the overactive bladder with oral anticholinergic drugs along with CIC [10]; unfortunately, not all patients respond to anticholinergics and, moreover, CIC carries a high risk for chronic urinary tract infection. If these strategies fail to respond, the patients may undergo surgical procedures [11, 12] but the side effects are not negligible; for example, bladder augmentation with gastrointestinal segments which is a common procedure performed on these patients may lead to metabolic abnormalities such as metabolic acidosis, increased risk of calculi production and mucus formation, and enhanced risk of malignancy [13]. Electrical stimulation as a treatment option for urinary incontinence was first introduced by Caldwell and colleagues [3]. Since then, many other investigators around the world have used this treatment modality for a variety of urological conditions; however, there is not much published data considering the use of this therapy in children with MMC. The primary aim of this study was to assess the effectiveness of transcutaneous FES on resolution of urinary incontinence in pediatric patients with myelomeningocele. Previously, we have observed promising results from this treatment modality in a pilot study [5]; this randomized study substantiates our former report. The results demonstrate the improvement of daily incontinence score in treatment group after FES therapy compared to the sham stimulation group. Interestingly, the DLPP was improved significantly after applying electrical stimulation. Of UDS parameters, MMBC was also increased compared to the sham stimulation group. The rationale behind using FES in overactive bladder is the observation that FES of pelvic floor muscles can effectively inhibit the detrusor overactivity [14, 15], but unlike the drug therapy, it does not interact with cholinergic receptors [16, 17]. It is suggested that the electrical stimulation recruits the rapid conduction nerve fibers and thereby causes the hypertrophy of striated muscles of pelvic floor, including the external urethral sphincter. Another mechanism which is postulated is the activation of hypogastric inhibitory neural fibers to the bladder and central inhibition of ascending afferent pathway from the bladder. None of these reflex pathways are activated during the voluntary contraction of the pelvic floor muscles [18]. In this study, all the patients had an organic neurologic insult (MMC). Our findings are not solely based on the
Pediatr Surg Int (2014) 30:663–668
subjective patient satisfaction questionnaires. In fact, to evaluate the patient improvement, we have assessed both the subjective and objective (UDS) measures regarding the chief complaint, i.e., urinary incontinence, and thus our results are more to be relied upon. The number of wet nights was lower in comparison with the control group. The patients’ caregivers also reported a lower frequency of pad changing after FES therapy compared to the sham stimulation group. The UDS findings are consistent with subjective reports. We observed an improvement in both UDS parameters, although FES showed to be more effective in increasing DLPP. None of the patients reported any serious side effect during or after treatment. There is not much published study considering the use of transcutaneous electrical stimulation in treatment of urinary incontinence caused by MMC. However, its ability to enhance the quality of life of patients in a number of urologic diseases is proved by investigators. Tomonori and colleagues reported the use of electrical stimulation in urinary incontinence after radical prostatectomy in adult patients results in earlier recovery though it does not change the final result. They suggested that a combination of pelvic floor muscle exercises and electrical stimulation in the first 3–6 months after radical prostatectomy may help the patients to gain continence earlier [18]. In a study by Radziszewski, the effect of transcutaneous electrical stimulation on urinary incontinence in patients after spinal cord injury has been evaluated. Patients underwent 30 sessions of electrical stimulation (five sessions per week). The outcomes of electrical stimulation were assessed by comparing the results of urodynamic study performed before treatment, immediately on completion of the treatment and at 24 months post-treatment. Results showed that 6 weeks of transcutaneous electrical stimulation can effectively improve urinary tract function. Moreover, improved urinary tract function is seen 2 years following completion of the electrical stimulation treatment [19]. In a single-blind randomized trial, Wang and colleagues have compared the efficacy of three treatments: pelvic floor muscle training, biofeedback-assisted pelvic floor muscle training, and electrical stimulation in management of overactive bladder. The results show that electrical stimulation is the most effective treatment among the three to improve the subjective measures of quality of life [20]. This study shows that the use of FES is quite successful in improving both the subjective complaints and objective measures in urinary incontinence caused by MMC. However, larger prospective trials with longer-term follow-up are needed to include this modality in management algorithms for MMC patients. However, this preliminary data in conjunction with our previous study show that this
667
treatment might be quite effective in the management of urinary incontinence in MMC patients.
Conclusion This type of electrical stimulation is safe, effective, reproducible, noninvasive, and cost-effective modality to improve urinary incontinence in children with history of MMC and neuropathic urinary incontinence and also can be used at home. According to our previous study, the FES therapy could be performed every 6 months or more and whenever the symptoms relapsed. Acknowledgments We are highly grateful to Dr. Kourosh Afshar Associate Professor of Pediatric Urology at the Department of Urology, British Columbia’s Children’s Hospital, Vancouver, Canada, for his final editing and invaluable comments on this manuscript. Conflict of interest
None.
References 1. Manning SM, Jennings R, Madsen JR (2000) Pathophysiology, prevention, and potential treatment of neural tube defects. Ment Retard Dev Disabil Res Rev 6(1):6–14 2. Zickler CF, Richardson V (2004) Achieving continence in children with neurogenic bowel and bladder. J Pediatr Health Care 18:276–283 3. Caldwell KP (1963) The electrical control of sphincter incompetence. Lancet 2:174–175 4. Cheˆne G, Mansoor A, Jacquetin B, Mellier G, Douvier S, Sergent F et al (2013) Female urinary incontinence and intravaginal electrical stimulation: an observational prospective study. Eur J Obstet Gynecol Reprod Biol 170(1):275–280. doi:10.1016/j. ejogrb 5. Kajbafzadeh A-M, Sharifi-Rad L, Dianat S (2010) Efficacy of transcutaneous functional electrical stimulation on urinary incontinence in myelomeningocele: results of a pilot study. Int Braz J Urol 36(5):614–620 6. Schurch B, Stohrer M, Kramer G, Schmid DM, Gaul G, Hauri D (2000) Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? preliminary results. J Urol 164:692–697 7. Neveus T, von Gontard A, Hoebeke P, Hjalmas K, Bauer S, Bower W et al (2006) 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 176:314–324 8. Baradaran N, Ahmadi H, Nejat F, El Khashab M, Mahdavi A (2008) Nonneural congenital abnormalities concurring with myelomeningocele: report of 17 cases and review of current theories. Pediatr Neurosurg 44:353–359. doi:10.1159/000149900 9. Larijani FJ, Moghtaderi M, Hajizadeh N, Assadi F (2013) Preventing kidney injury in children with neurogenic bladder dysfunction. Int J Prev Med Dec 4(12):1359–1364 10. Lehnert T, Weisser M, Till H, Rolle U (2012) The effects of longterm medical treatment combined with clean intermittent catheterization in children with neurogenic detrusor overactivity. Int Urol Nephrol Apr 44(2):335–341. doi:10.1007/s11255-011-0030-y
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668 11. Kajbafzadeh AM, Ahmadi H, Montaser-Kouhsari L, Sharifi-Rad L, Nejat F, Bazargan-Hejazi S (2011) Intravesical electromotive botulinum toxin type A administration–part II: clinical application. Urology 77(2):439–445. doi:10.1016/j.urology.2010.06.003 12. MacDonald R, Fink HA, Huckabay C, Monga M, Wilt TJ (2007) Botulinum toxin for treatment of urinary incontinence due to detrusor overactivity: a systematic review of effectiveness and adverse effects. Spinal Cord 45:535–541 13. McDougal WS (1992) Metabolic complications of urinary intestinal diversion. J Urol 147:1199–1208 14. Schreiner L, Santos TG, Souza AB, Nygaard CC, Silva Filho IG (2013) Electrical stimulation for urinary incontinence in women: a systematic review. Int Braz J Urol 39(4):454–464. doi:10.1590/ S1677-5538.IBJU.2013.04.02 15. Knorst MR, Resende TL, Santos TG, Goldim JR (2013) The effect of outpatient physical therapy intervention on pelvic floor muscles in women with urinary incontinence. Braz J Phys Ther 17(5):442–449. doi:10.1590/S1413-35552012005000117
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Pediatr Surg Int (2014) 30:663–668 16. Brubaker L (2000) Electrical stimulation in overactive bladder. Urology 55:17–23 discussion 31–2 17. Fall M, Lindstro¨m S (1991) Functional electrical stimulation: physiological basis and clinical principles. Urol Clin North Am 18(2):393–407 18. Yamanishi T, Mizuno T, Watanabe M, Honda M, Yoshida K (2007) Randomized, placebo controlled study of electrical stimulation with pelvic floor muscle training for severe urinary incontinence after radical prostatectomy. J Urol 184(5): 2007–2012 19. Radziszewski K (2013) Outcomes of electrical stimulation of the neurogenic bladder: results of a two-year follow-up study. NeuroRehabilitation 32(4):867–873. doi:10.3233/NRE-130911 20. Wang AC, Wang Y-Y, Chen M-C (2004) Single-blind, randomized trial of pelvic floor muscle training, biofeedback-assisted pelvic floor muscle training, and electrical stimulation in the management of overactive bladder. Urology 63:61–66
ORIGINAL ARTICLE
Functional electrical stimulation for management of urinary incontinence in children with myelomeningocele: a randomized trial Abdol-Mohammad Kajbafzadeh • Lida Sharifi-Rad Seyedeh Sanam Ladi Seyedian • Ahmad Masoumi
•
Accepted: 2 April 2014 / Published online: 17 April 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose To report the efficacy of transcutaneous functional electrical stimulation (FES) in children with refractory neuropathic urinary incontinence secondary to myelomeningocele (MMC). Methods Thirty children with history of MMC (12 girls and 18 boys, mean age 6.7 ± 3.6 years) with refractory urinary incontinence were enrolled in this study. They were randomly allocated to treatment (FES, 15 children) and control (sham stimulation, 15 children) groups. All patients underwent urodynamic study (UDS) before and 6 months after FES considering detrusor leak point pressure (DLPP), mean maximal detrusor pressure, and mean maximal bladder capacity. Daily incontinence score, frequency of pad changing, and enuresis were also assessed before and 6 months after treatment. A 15-course FES was performed for 15 min and 3 times per week. Children were followed for at least 6 months. Results Of UDS variables, DLPP increased significantly from 32 ± 10.7 cmH2O before treatment to 55.6 ± 24.9 cmH2O in treatment group after 6 months (P \ 0.03). Daily incontinence score (range 0–3) improved significantly in treatment group from 2.7 ± 0.4 before
treatment to 1.3 ± 0.9 after treatment compared with sham stimulation group (P \ 0.02). Conclusion This type of electrical stimulation is a safe, noninvasive, and effective modality to improve urinary incontinence in myelomeningocele children and can be used at home. Keywords Functional electrical stimulation Myelomeningocele Neuropathic bladder Urinary incontinence Abbreviations FES Functional electrical stimulation MMC Myelomeningocele UDS Urodynamic study DLPP Detrusor leak point pressure MMBC Mean maximal bladder capacity MMDP Mean maximal detrusor pressure ICCS International children’s continent society
Introduction
A.-M. Kajbafzadeh (&) S. S. Ladi Seyedian A. Masoumi Pediatric Urology Research Center and Department of Pediatric Urology, Children’s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, 62 Qarib St, Keshavarz Blvd, 1419733151 Tehran, Iran (IRI) e-mail: [email protected] L. Sharifi-Rad Department of Physical Therapy, Children’s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran (IRI)
Myelomeningocele (MMC) is the most common form of spina bifida. Live born infants with MMC have a mortality rate of about 10 % [1]. The survivors will suffer from numerous complications including different types of neurological deficits, paralysis, and bladder and bowel dysfunction. This is important to note that renal failure is the leading cause of death after the first few years of life; therefore, early urologic management of these patients is essential [2]. Medical therapy with anticholinergic drugs either alone or with clean intermittent catheterization (CIC)
123
664
is the first line of treatment in MMC patients. This approach is the most effective treatment for these children; however, different aggressive managements are recommended for patients who are not responding well to supportive therapy. Electrical stimulation has been introduced as an alternative treatment modality for a number of urologic complaints since 1963 [3]. It is hypothesized that electrical stimulation causes action potential in the afferent fibers of pudendal nerve in which lead to efferent outflow causing contraction of the striated pelvic floor muscles [4]. Moreover, detrusor inhibitory reflex might be activated by electrical stimulation. Functional electrical stimulation (FES) is a type of electrical current which uses for the excitable tissue in order to improve function that is lost in neurologically damaged. Our prior study looked at the use of transcutaneous FES in the treatment of urinary incontinence in children with MMC [5]. We reported a decrease in urinary incontinence score after FES therapy. Most of the results proved to be long term, however; there were patients who needed to repeat FES therapy. As this method was introduced for the first time in our previous study, the aim of this study was to reassure the effects of FES therapy on management of urinary incontinence in MMC children by comparing the results with the sham stimulation group.
Pediatr Surg Int (2014) 30:663–668
Patients Twelve girls and eighteen boys with MMC between 3 and 13 years of age, with moderate-to-severe urinary incontinence (score 2 and 3) resistant to conventional treatment (demonstrating adverse effects or unsatisfactory success rate), requiring CIC every 3–4 h and use of pads were registered for this single-center study. All patients were on CIC and anticholinergics. Moreover, they were on maximum medical therapy without acceptable response to medication. Botox or any other therapy had not been tried for all patients previously. In addition, patients who had constipation had been managed with diet and mild laxatives. All patients underwent a detailed medical history and physical examination, urinalysis, renal ultrasonography, and urodynamic study (UDS). Mean maximal bladder capacity (MMBC), mean maximal detrusor pressure (MMDP), and mean detrusor leak point pressure (DLPP) were recorded according to International Children’s Continence Society (ICCS) recommendations [7]. The 30 patients eligible for the study were randomly allocated to treatment (FES, 15 children) and control (sham stimulation, 15 children) groups. Patients were unaware of the group assignment and so was the urodynamic nurse practitioner. They were followed up for the next 6 months.
Urodynamic measurement Materials and methods We included 30 MMC children who were referred to our outpatient pediatric urology clinic at Children’s Hospital Medical Center, Tehran University of Medical Sciences, in this prospective and randomized (balance block randomization) trial study between August 2009 and September 2012. Children with additional neurologic abnormalities other than MMC sequelae and children with underlying medical conditions (metabolic diseases, anorectal and urogenital malformations, previous urogenital surgery) were excluded from the study. All parents were instructed to fill out a voiding diary with providing data about the episodes of enuresis (the number of nights that the child involuntarily micturates during sleep in a 1-week period), frequency of pad changing (the number of wetting episodes between 2 consecutive CICs). The daily incontinence score was recorded on a 0–3 scale, as described by Schurch et al. [6]: score 0, completely dry; 1, wet once a day, usually at night (mild); 2, wet for \50 % of the time between CIC (moderate); and 3, wet for [50 % of the time between CIC (severe). A decrement of 2 or more degrees in the daytime incontinence score was considered as ‘‘improvement.’’
123
The UDS evaluations (F.M. Wiest Medizintechnik, GmbH, Unterhaching, Germany) were complied with regard to ICCS recommendations in all patients in supine position. A double-lumen catheter and rectal balloon catheter were used to measure the intravesical and intraabdominal pressure simultaneously. Patch electrodes in the perineal area recorded EMG. Special attention was given to DLPP, MMDP, and MMBC. The same protocol was used for the UDSs performed 6 months after FES courses. Patients were asked to discontinue their anticholinergic medication intake at least 7 days prior to both UDS sessions. Success was defined as any significant reduction in each of these UDS parameters compared to our sham stimulation group. In addition, subjective success was assessed using a voiding diary and the results compared between both groups.
Functional electrical stimulation Following pretreatment UDS, anticholinergic medication and CIC were continued. FES was applied for a total of 15 sessions, 15 min each and three times per week. The same electrical stimulation device (Model ISOTERAP 786 DS?,
Pediatr Surg Int (2014) 30:663–668
665 Table 1 Demographic and clinical characteristics of children in the treatment and control groups
Age (years)
Case15
Control15
5.9
7.5
Gender (%) Female
7 (46 %)
5 (34 %)
Male
8 (54 %)
10 (66 %)
5 (34 %)
4 (26 %)
7 (46 %) 3 (20 %)
6 (40 %) 5 (34 %)
4 (26 %)
3 (20 %)
2 (13 %)
3 (20 %)
MMC level no. (%) Sacral Lower lumbar Upper lumbar Movement disorder no. (%) Paraplegia Proximal weakness
Fig. 1 Applying of positive and negative electrodes for FES
Distal weakness
6 (40 %)
7 (46 %)
Normal
3 (20 %)
2 (13 %)
6 (40 %)
7 (46 %)
Hip disorder
4 (26 %)
2 (13 %)
Hydrocephalus
2 (13 %)
4 (26 %)
History of concurrent disability no. (%) Club foot
Tavanbakhsh Novin Tehran, Iran) was used for all patients. The FES delivered a 40 Hz frequency (to cover both the irritative and obstructive symptoms and stimulate striated muscle fibers and urethral sphincter in pelvic floor), a duration of 250 ls, with hold and rest time of 2 s with adjustable amplitude (range 20–65 mA).The FES was applied according to the method of our previous study by a physiotherapist [5]. Two rectangular self-adhesive (2.5 9 3.5 cm) electrodes were applied in which positive electrode was placed on the skin above the pubic symphysis, and the negative one was placed on the skin under urethra (in female over the labia major and in male under the scrotum) (Fig 1). The intensity was increased until the child reported a strong but comfortable level of muscle contractions in the treatment group. In smaller children, an intensity setting of \30 mA was applied. Maximum current intensity was below the pain threshold and well tolerated by the children in the treatment group. All patients in the treatment group received FES for 15 courses, 15 min each and 3 times per week. Patients in control group also underwent an identical setting of procedure without increasing the intensity and conveying the FES therapy for 15 courses, 15 min each session and 3 times per week. After completion of FES courses, patients in both groups were followed for next 6 months.
Statistical analysis Statistical analysis was performed with statistical package of social science software version 17 (SPSS Inc., Chicago, IL, USA). Chi-square test or Wilcoxon signed-rank test
MMC myelomeningocele
was executed for nonparametric statistical comparisons before and after the treatment in both cohorts. Mann– Whitney U test and Student’s t test were performed wherever applicable to compare the values between two groups. Data are expressed as mean ± SD, and P \ 0.05 was considered statically significant.
Results A total of 30 MMC children with mean age of 6.7 ± 3.6 years were enrolled in this study. The treatment group comprised of 8 boys and 7 girls with mean age of 5.9 ± 3.5 years and control group included 10 boys and 5 girls with mean age of 7.4 ± 3.6 years. Both treatment and control groups were similar with regard to age, gender, and pre-intervention voiding diary (P [ 0.05). All patients in both groups completed the study protocol until follow-up. The baseline demographic data of treatment and control groups are shown in Table 1. Daily incontinence score (range 0–3) improved significantly in treatment group from 2.7 ± 0.4 before treatment to 1.3 ± 0.9 after treatment compared with sham stimulation group (P \ 0.02, Table 2). Comparing the two groups, 3 of 15 patients in treatment group became completely dry between two consecutive CICs and daily incontinence score was improved from 3 to 1 in four patients in treatment group at follow-up. Two of 15 patients in treatment group and 8/15
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Table 2 Urodynamic and voiding diary parameters of children before and after 6 months following FES (treatment) and sham stimulation (control) Variables
Groups
Before FES therapy
6 mon. after FES therapy
Pc value
Detrusor leak point pressure (cmH2O)
Treatment
32 ± 10.7
55.6 ± 24.9
0.000
control
33.5 ± 9
37 ± 11
0.261
Pab
0.682
0.03
Mean maximal bladder capacity
Treatment
183 ± 91
260 ± 87
0.01
control
193 ± 78
204 ± 87
0.433
(ml)
Pab
0.765
0.110
Mean maximal detrusor pressure (cmH2O)
Treatment
59 ± 31
38 ± 16
0.004
control
44 ± 22
50 ± 27
0.316
Pab
0.145
0.158
Mean detrusor compliance (ml/cmH2O)
Treatment control
6.7 ± 4.9 8.3 ± 4.7
12.4 ± 5.7 10.2 ± 5.2
Pab
0.386
0.286
Daily incontinence score (range 0–3)
Treatment
2.7 ± 0.4
1.3 ± 0.9
0.000
control
2.5 ± 0.5
2 ± 0.6
0.105
P
ab
0.002 0.018
0.438
0.02
Frequency of pad changing (times/day)
Treatment
5.2 ± 1.6
2.4 ± 1.4
0.000
control
4.3 ± 1.7
3.5 ± 1.6
0.005
Pab
0.169
0.03
Enuresis (night/week)
Treatment
4.1 ± 2.5
2.7 ± 0.9
0.02
control
5.6 ± 2.7
4.5 ± 3.3
0.116
Pab
0.191
0.205
Bold numbers show significant P values a
Mann–Whitney U test, bStudent’s t test, cWilcoxon signed-rank test
patients in control group remained unchanged for their daily incontinence score (P \ 0.02). Frequency of pad changing was significantly decreased in treatment group in comparison with control group. This characteristic decreased from (5.2 ± 1.6 times/day versus 4.3 ± 1.7 times/day) before FES therapy to (2.4 ± 1.4 times/day versus 3.5 ± 1.6 times/day) after FES therapy at follow-up (P \ 0.03). Of UDS parameters, DLPP increased from 32 ± 10.7 cmH2O before treatment to 55.6 ± 24.9 cmH2O after 6 months of FES therapy (P \ 0.03). MMDP decreased in treatment group compared with controls (38 ± 16 versus 50 ± 27 cmH2O), but this finding was not significant. The details of voiding diary and UDS parameters before and after treatment are shown in Table 2. Moreover, children and their parents did not report any significant adverse effects after the treatment.
Discussion Myelomeningocele is one of the most serious congenital defects with an incidence of 1.6 per 1,000 live births in Iran
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[8]. This defect is caused by the inability of neural tube to close during early gestational period and usually presents by lower limb paresis and bowel and bladder dysfunction. One of the most serious complications of MMC is renal damage due to the poor bladder compliance and detrusor overactivity [9]. Thus, early treatment of bladder dysfunction is crucial to avoid these sequelae. Currently most urologists treat the overactive bladder with oral anticholinergic drugs along with CIC [10]; unfortunately, not all patients respond to anticholinergics and, moreover, CIC carries a high risk for chronic urinary tract infection. If these strategies fail to respond, the patients may undergo surgical procedures [11, 12] but the side effects are not negligible; for example, bladder augmentation with gastrointestinal segments which is a common procedure performed on these patients may lead to metabolic abnormalities such as metabolic acidosis, increased risk of calculi production and mucus formation, and enhanced risk of malignancy [13]. Electrical stimulation as a treatment option for urinary incontinence was first introduced by Caldwell and colleagues [3]. Since then, many other investigators around the world have used this treatment modality for a variety of urological conditions; however, there is not much published data considering the use of this therapy in children with MMC. The primary aim of this study was to assess the effectiveness of transcutaneous FES on resolution of urinary incontinence in pediatric patients with myelomeningocele. Previously, we have observed promising results from this treatment modality in a pilot study [5]; this randomized study substantiates our former report. The results demonstrate the improvement of daily incontinence score in treatment group after FES therapy compared to the sham stimulation group. Interestingly, the DLPP was improved significantly after applying electrical stimulation. Of UDS parameters, MMBC was also increased compared to the sham stimulation group. The rationale behind using FES in overactive bladder is the observation that FES of pelvic floor muscles can effectively inhibit the detrusor overactivity [14, 15], but unlike the drug therapy, it does not interact with cholinergic receptors [16, 17]. It is suggested that the electrical stimulation recruits the rapid conduction nerve fibers and thereby causes the hypertrophy of striated muscles of pelvic floor, including the external urethral sphincter. Another mechanism which is postulated is the activation of hypogastric inhibitory neural fibers to the bladder and central inhibition of ascending afferent pathway from the bladder. None of these reflex pathways are activated during the voluntary contraction of the pelvic floor muscles [18]. In this study, all the patients had an organic neurologic insult (MMC). Our findings are not solely based on the
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subjective patient satisfaction questionnaires. In fact, to evaluate the patient improvement, we have assessed both the subjective and objective (UDS) measures regarding the chief complaint, i.e., urinary incontinence, and thus our results are more to be relied upon. The number of wet nights was lower in comparison with the control group. The patients’ caregivers also reported a lower frequency of pad changing after FES therapy compared to the sham stimulation group. The UDS findings are consistent with subjective reports. We observed an improvement in both UDS parameters, although FES showed to be more effective in increasing DLPP. None of the patients reported any serious side effect during or after treatment. There is not much published study considering the use of transcutaneous electrical stimulation in treatment of urinary incontinence caused by MMC. However, its ability to enhance the quality of life of patients in a number of urologic diseases is proved by investigators. Tomonori and colleagues reported the use of electrical stimulation in urinary incontinence after radical prostatectomy in adult patients results in earlier recovery though it does not change the final result. They suggested that a combination of pelvic floor muscle exercises and electrical stimulation in the first 3–6 months after radical prostatectomy may help the patients to gain continence earlier [18]. In a study by Radziszewski, the effect of transcutaneous electrical stimulation on urinary incontinence in patients after spinal cord injury has been evaluated. Patients underwent 30 sessions of electrical stimulation (five sessions per week). The outcomes of electrical stimulation were assessed by comparing the results of urodynamic study performed before treatment, immediately on completion of the treatment and at 24 months post-treatment. Results showed that 6 weeks of transcutaneous electrical stimulation can effectively improve urinary tract function. Moreover, improved urinary tract function is seen 2 years following completion of the electrical stimulation treatment [19]. In a single-blind randomized trial, Wang and colleagues have compared the efficacy of three treatments: pelvic floor muscle training, biofeedback-assisted pelvic floor muscle training, and electrical stimulation in management of overactive bladder. The results show that electrical stimulation is the most effective treatment among the three to improve the subjective measures of quality of life [20]. This study shows that the use of FES is quite successful in improving both the subjective complaints and objective measures in urinary incontinence caused by MMC. However, larger prospective trials with longer-term follow-up are needed to include this modality in management algorithms for MMC patients. However, this preliminary data in conjunction with our previous study show that this
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treatment might be quite effective in the management of urinary incontinence in MMC patients.
Conclusion This type of electrical stimulation is safe, effective, reproducible, noninvasive, and cost-effective modality to improve urinary incontinence in children with history of MMC and neuropathic urinary incontinence and also can be used at home. According to our previous study, the FES therapy could be performed every 6 months or more and whenever the symptoms relapsed. Acknowledgments We are highly grateful to Dr. Kourosh Afshar Associate Professor of Pediatric Urology at the Department of Urology, British Columbia’s Children’s Hospital, Vancouver, Canada, for his final editing and invaluable comments on this manuscript. Conflict of interest
None.
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