Elsevier

Journal of Pediatric Urology

Volume 12, Issue 2, April 2016, Pages 118.e1-118.e6
Journal of Pediatric Urology

The role of urinary nerve growth factor for the diagnosis and assessment of the biofeedback success in children with dysfunctional voiding

https://doi.org/10.1016/j.jpurol.2015.09.015Get rights and content

Summary

Introduction

Dysfunctional voiding (DV) occurs in neurologically normal children who are not able to establish brain control on detrusor muscle contractions (DMCs). It is also reported to be the result of incorrect voiding habits during toilet training. Children contract pelvic floor muscles (PFMs) to suppress DMC and DV begins. Urinary nerve growth factor (uNGF) is necessary for the synthesis and regulation of neurotransmitters, development of dorsal root ganglia (sensory neurons), and development of sympathetic cells during embryonic and post-natal life. uNGF has also a role in the intracellular signal transduction in nerve cells towards the target organ. To our knowledge, no study has investigated the association between uNGF, biofeedback treatment and DV in children.

Objectives

The aim was to examine the potential effect of uNGF in the assessment of the effectiveness of biofeedback success in children with lower urinary tract disorders.

Study design

Fifty-two children with the suspicion of DV and 48 children from a primary school reporting no urinary complaints were enrolled in this study from October 2010 to April 2013 in the Urology Department. uNGF levels were compared.

Results

The mean uNGF/creatinine (Cr) level was 0.23 ± 0.26 in the control group and 0.96 ± 0.88 in the DV group (p < 0.001). The mean uNGF/Cr levels in the DV group at baseline and at the end of biofeedback therapy at 6 and 12 months were 0.90 ± 0.78, 0.26 ± 0.32, and 0.40 ± 0.50, respectively (p < 0.001) (Figure).

Discussion

To our knowledge this study is the first to show the correlations between uNGF levels and biofeedback therapy in children with DV. Tissue NGF in 12 patients with overactive bladder (OAB)/detrusor overactivity and 15 healthy women was previously compared and it was suggested that there was no correlation between bladder tissue NGF and OAB. uNGF levels in the bladder in patients with interstitial cystitis and idiopathic sensorial urgency were evaluated previously, and uNGF levels reported. Similar to these reports, most of the previous studies handled uNGF in patients with diseases such as interstitial cystitis, OAB, urinary tract infections, urolithiasis, spinal cord injury, and prostate cancer, and found significantly higher uNGF levels. These studies were generally in adults. A previous study about uNGF comprised 40 children with OAB, in contrast to other studies. According to this study, 40 children diagnosed with OAB were administered anti-muscarinic therapy (oxybutynin 0.3–0.5 mg/kg/day). It was reported that uNGF/Cr levels of the OAB group were higher than control group. In the current study, we evaluated the uNGF difference in DV and the effect of biofeedback treatment on uNGF levels.

Conclusions

uNGF levels were higher in children with DV and decreased after biofeedback therapy. uNGF levels could be used for the diagnosis and the assessment of biofeedback success in these children.

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Figure. The mean uNGF/Cr levels in the DV group at the baseline, at the end of biofeedback therapy (6 and 12 months).

Introduction

Dysfunctional voiding (DV) occurs in neurologically normal children who are not able to establish brain control on detrusor muscle contractions (DMCs) [1]. It is also reported to be the result of incorrect voiding habits during toilet training [1]. Children contract pelvic floor muscles (PFMs) to suppress DMCs and DV begins. The common symptoms of DV are daytime urinary incontinence, enuresis, urgency, frequency, infrequency, urgency incontinence, straining, pain while urinating, staccato voiding, and constipation [1]. Abnormal DMCs and PFM contractions cause post-void residual urine (PVR). Urinary tract infections (UTIs) and vesicoureteral reflux (VUR) occur due to PVR. Renal parenchymal damage and chronic renal failure can also be seen as a result of frequent UTIs and VUR [2].

DV has two subgroups: storage disorders and emptying disorders. Overactive bladder (OAB) syndrome, urinary incontinence, and giggle incontinence are the storage disorders. Lazy bladder syndrome, Hinmann syndrome, and post-micturition dribbling are the emptying disorders [3]. The diagnosis of DV is made with the dysfunctional voiding and incontinence symptom scoring system (DVISSS), a bladder diary, and some urodynamic studies. Within a confidence interval of 96.2%, patients with a DVISSS score of 8.5 or greater had DV, with a sensitivity of 90% and a specificity of 90% [4]. Urodynamic studies for the diagnose of DV usually include uroflowmetry, electromyography (UF-EMG), and PVR measurements [4], [5].

Urinary nerve growth factor (uNGF) is necessary for the synthesis and regulation of neurotransmitters, development of dorsal root ganglia (sensory neurons), and development of sympathetic cells during embryonic and post-natal life. uNGF also has a role in intracellular signal transduction in nerve cells towards the target organ. As a response to inflammatory processes, mast cells, urothelium, and detrusor muscles can also release uNGF [6], [7]. There are some studies about uNGF and voiding dysfunction. However, all of these studies are about OAB in adults and children. Elevated uNGF levels are reported in OAB, interstitial cystitis, painful bladder syndrome, detrusor over activity (DOA), bladder outlet obstruction (BOO), urinary tract cancer, ureteral stones, and UTIs [8], [9], [10]. To our knowledge, no study has investigated the association between uNGF, biofeedback treatment, and lower urinary tract disorders (LUTDs) in children. In this study, we aimed to examine the potential effect of uNGF in the assessment of effectiveness of biofeedback success in children with DV.

Section snippets

Patients

This is a cross-sectional and quasi-experimental study. The institutional review board and ethics committee approved this study. Fifty-two children with the suspicion of DV and 48 children from a primary school reporting no urinary complaints were enrolled in this study from October 2010 to April 2013 at our Urology Department. They were between 5 and 15 years old. Initial evaluations of all the children started with taking the history and physical examination. Urine analysis, urine culture,

Statistical analysis

Statistical analysis was done using Statistical Package for Social Sciences 15.0 software (SPSS 15.0 for Windows, Chicago, IL, USA). Descriptive statistics were noted with numbers: mean ± standard deviation with minimum–maximum. Shapiro–Wilk, Kurtosis, and skewness tests were used to assess the normalization of the variables. The Mann–Whitney U test was used to compare groups. A p value < 0.05 was accepted to be statistically significant. We also performed Bonferoni–corrected pairwise

Results

The mean ages of the control and patients groups were 9.26 ± 2.87 and 8.84 ± 2.54 years, respectively (p > 0.05). There were 19 girls and 29 boys in the control group and 30 girls and nine boys in patients group. The DVISSS questions answered for the patient group and the control group are depicted in Fig. 1.

uNGF and uNGF/Cr levels were significantly higher in the DV group than in the control group. The mean uNGF/Cr level was 0.96 ± 0.88 (0.01–4.11) in DV group and 0.23 ± 0.26 (0.003–1.20) in

Discussion

The bladders of the children are affected at different levels due to the different periods and severity of DV. If DV continues for a long time, the upper urinary tract begins to be affected and life-threatening complications such as chronic kidney disease may emerge.

To our knowledge, this study is the first to show the correlation between uNGF levels and biofeedback therapies in children with DV. Birder et al. [12] compared tissue NGF levels between 12 patients with OAB/detrusor overactivity

Conclusion

uNGF levels were higher in children with DV and decreased after biofeedback therapies. Despite the diagnosis and determination of treatment, effectiveness of DV should be based on clinical assessment; the uNGF levels can be used as an adjunct tool to explain the pathophysiology of DV.

Conflict of interest

None.

Funding

None.

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