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Int Neurourol J > Volume 27(1); 2023 > Article
Shim and Oh: Updates of Overactive Bladder in Pediatrics

ABSTRACT

Overactive bladder (OAB) is clinically defined as urinary urgency with or without urinary incontinence. It is associated with daytime frequency or constipation and has a prevalence of approximately 5%–12% among 5- to 10-year-olds. The appropriate functional exchange between the pontine micturition center, periaqueductal gray matter, and prefrontal cortex is important for proper micturition control. Several studies on pediatric cases observed a link between OAB and neuropsychiatric problems, such as anxiety, depression, and attention deficit, and treatment of these comorbidities improved patient symptoms. In this review, we present the pathophysiology of OAB, its associated conditions, and aspects related to updates in OAB treatment, and we propose a step-by-step treatment approach following this sequence: behavioral therapy, medical treatment, and invasive treatment. Although anticholinergic drugs are the mainstay of OAB medical treatment, beta-3 agonists and alpha-blockers are now recommended as a result of significant advancements in pharmacologic treatment in the last 10 years. Electrical stimulation techniques and botulinum toxin are also effective and can be used, especially in conventional treatment-refractory cases.

INTRODUCTION

Daytime lower urinary tract dysfunction (LUTD) is a common clinical disorder in the pediatric population, with a prevalence of 1%–20% [15], and comprises 40% of outpatient pediatric urologist clinic visits [6]. LUTD primarily results from dysfunction of the voiding phase, filling phase, or both and can vary in severity. Its 2 main types are overactive bladder (OAB) and dysfunctional voiding (DV).
In children, LUTD mainly results from delayed or incomplete maturation of the lower urinary tract complex (bladder sphincter). The pons is responsible for detrusor and sphincter coordination, while the cortex controls micturition reflex inhibition and voluntary micturition initiation [7]. Therefore, incomplete cortical maturation is proposed as the main reason for pediatric OAB, whereas failure of detrusor and sphincter coordination may be the primary reason for DV [8].
Among storage-phase dysfunctions, OAB is the most common and usually occurs in children between 5 and 7 years old, especially in boys [9]. According to the International Children’s Continence Society guidelines, OAB is defined as urinary urgency, usually accompanied by the frequency of urinary incontinence with or without urinary incontinence, and without any signs of urinary tract infection (UTI) or any other obvious pathology [10]. Some children habitually endure the urge to urinate by performing holding maneuvers, such as Vincent’s curtsy or squatting, leading to voiding postponement and sometimes bladder overdistention. Owing to a high-pressure bladder, recurrent UTI or vesicoureteral reflux may be common [7]. Another important risk factor for OAB that should be assessed separately is constipation. Toilet training involves adequate bowel and bladder storage and emptying at an appropriate place and time and is generally performed at 3–4 years of age. Toilet training problems, when accompanied by incontinence, can lead to low self-esteem in children [8]. In many instances, this can place undue stress on caregivers as a result of more frequent trips to the toilet.

PATHOPHYSIOLOGICAL FEATURES

Urgency

Urinary urgency is the cornerstone symptom for diagnosing OAB. When there is no urine in the bladder, the bladder pressure is almost zero; this rises to 5–10 cm H2O when 30–50 mL of urine accumulates in the bladder. An additional 200–300 mL of collected urine further raises the pressure slightly, and constant intravesical pressure is maintained due to the inherent tone of the bladder wall (compliance) [11]. Urinary contractions usually occur when the bladder is partially filled and disappear after a few seconds. As the bladder continues to fill, the voiding reflex frequency gradually increases, and detrusor contraction intensifies. Patients with OAB who experience a pathologically distinct urge to urinate resulting from a full bladder deviate from this norm and perceive micturition contractions as more intense than normal. This finding is thought to be related to changes in the threshold at which these contractions occur during partial bladder filling (Fig. 1).
The sensation of bladder fullness is transmitted through 2 different types of afferent fibers. Aδ-fibers are activated by low-intensity stimuli, such as bladder distention, and transmit normal sensations of bladder fullness. In contrast, C-fibers, which have a higher threshold, usually transmit pain sensations and play an important role in bladder diseases [12]. Not all patients with urinary urgency experience detrusor overactivity or sense bladder contractions, which are measured by 24-hour urodynamic studies (UDS). Therefore, detrusor overactivity is not a key defining feature of urinary urgency. However, Bael et al. [13] demonstrated that the use of UDS in children with OAB is limited.

Neural Factors

Normal development and immaturity

The pathophysiology of OAB has not been thoroughly studied and is believed to be multifactorial. One representative theory proposes that urinary urgency and related symptoms result from the immaturity of the neural centers controlling urination [14], which is supported by the fact that voiding ability improves with age. In the first few months of life, a child’s voiding pattern is characterized by an intermittent urinary flow [15]. During this period, micturition is controlled by the brainstem, similar to involuntary reflex voiding. At ages 1–3 years, voiding ability improves as the cortical inhibitory pathway, periaqueductal gray matter (PAG), anterior cingulate gyrus (ACG), and autonomic/somatic nervous system develop [6]. As the child matures, the prefrontal cortex (PFC) develops top-down control over more primitive afferent brain pathways, such as the limbic and paralimbic systems. Frontal lobe maturation occurs throughout childhood and adolescence until the mid-20s, which explains the gradual resolution of OAB as children age. Chung et al. [16] reported an age-dependent decrease in OAB prevalence from approximately 23% at 5 years to 12.2% at 13 years of age.

ACG hyperactivation and pontine center deactivation

Urgency is defined as the “intense desire” to urinate, suggesting that higher brain centers are involved in this process. Functional magnetic resonance imaging (MRI) and positron emission tomography revealed differences in brain lesions and activity between patients with normal LUT function and those with detrusor overactivity [17,18]. During the storage phase, the PAG, which is located in the midbrain, receives information from the medial PFC, ACG, thalamus/hypothalamus, and insula (Fig. 2) [17].
An MRI-based study revealed that a small bladder volume is associated with decreased ACG activity, and higher bladder volumes correlate with significantly increased ACG activity [14]. Patients with urgency have increased ACG activity and decreased PFC activity, which leads to more frequent bladder repletion and, therefore, the urge to void.

Neuropsychiatric Problems

While the pathophysiology of urgency has not been fully elucidated, the relationship between LUTD, behavioral aspects, and constipation reaffirms the close association of the bladder–gut–brain axis [19]. In a longitudinal study, anxiety disorder was observed in children as young as 6 months old, and up to one-third of social anxiety persisted until the age of 15 [20]. Functional MRI data revealed thinning of PFC lesions in children with refractory OAB, while cortical thickening was observed as a compensatory mechanism for anxiety in children with improved symptoms. A relationship between irritable bowel syndrome (IBS) and OAB has also been observed, especially in IBS with chronic constipation. Similar to OAB, psychiatric comorbidities are prevalent in children with IBS [21]. Evidence of cortical thinning in the frontal lobe of patients with IBS supports the possibility of these comorbidities [22].
Children who delay urination may experience behavioral problems. Similar to learning and psychiatric disorders, such as panic, anxiety, attention deficit hyperactivity disorder, and oppositional defiant disorder [19,23], voiding postponement may be the reason for behavioral problems. Children with oppositional defiant disorder sometimes refuse to go to the toilet, which leads to functional fecal incontinence [24]. Although only a few studies on the neuroassessment of these patients have been published, PFC hypoactivation should be suspected [25,26].

Constipation

Several pelvic organs share an afferent innervation pathway (e.g., hypogastric nerve) that enables the crosstalk of neurons innervating other organs [2729]. Children with OAB often experience urethral, vaginal, or penile discomfort, suggesting that pain is induced by a variety of anatomical lesions. Yoshimura et al. [30] reported that problems with the pelvic organs, such as the colon or uterus, affect urinary continence. Chronic colon distention due to constipation, which is a well-recognized cause of lower urinary tract symptoms (LUTS) in children, affects the bladder afferent signaling pathway, which prevents accurate recognition of the sensation of bladder fullness [31].

CLINICAL HISTORY AND PHYSICAL EXAMINATION

An in-depth medical history and physical examination should be performed when a child with OAB symptoms visits a hospital. Several papers have been published regarding the clinical workup of children with OAB [20,32]. When identifying symptoms suggestive of OAB, it is important to check for the presence of sacral dysraphism at the first examination. Excluding UTI from the diagnosis is also crucial and can be achieved by performing appropriate methods, such as urinalysis or, if necessary, a urine culture [20]. Checking for behaviors suggesting urgency (e.g., crossing of legs, running to the bathroom, grabbing the penis, rubbing the clitoris, squatting, or sitting on heels) is equally fundamental, and keeping a voiding diary may be necessary [33]. Abdominal palpation or radiographic assessment of constipation is paramount because parents are usually reluctant to admit that their child is constipated. In some children, a rectal diameter of approximately 3–4 cm suggests constipation, and this can be utilized instead of radiography [34]. Additionally, assessment of neuropsychiatric problems may be indicated for children, siblings, parents, and close relatives, as this can help clinicians immediately determine a child’s response to conventional treatment.
Over the past 20 years, several validated questionnaires have been developed to enable uniform history taking in children with LUTD. These questionnaires can help standardize clinical data reported in the literature and help clinicians measure outcomes. The followings are some of the validated questionnaires for evaluating LUTS in children:
  • (1) DV Symptom Score (first designed in 2000): This assessment tool is based on the American Urological Association Symptom Index [35].

  • (2) DV and Incontinence Scoring System: It consists of 14 questions, with a maximum score of 35+3 and a cutoff value of 9 points to determine abnormality [36].

  • (3) Pediatric Urinary Incontinence Quality of Life Score: Developed by Bower et al. [37], this tool has excellent internal validity, content validity, and test-retest reliability.

In addition to these, the Incontinence Symptom Index–Pediatric [38] and Child Behavior Checklist [39] can also be used. The Bristol stool chart [40] and Rome IV criteria [41] are references for evaluating bowel dysfunction. Because several LUTS may coexist, many children experience only partial symptom resolution with treatment. Therefore, the use of the abovementioned assessment tools may improve overall treatment benefits [32].

TREATMENT

Conservative Treatment

Urotherapy

Urotherapy is a nonsurgical, nonpharmacological approach (rehabilitation) that is considered a first-line treatment for OAB. Standard urotherapy begins with educating the child and family to explain and understand the child’s specific dysfunction. Motivation is an integral determinant of treatment success. A child who cannot anticipate the benefits of treating his or her dysfunction may not be ready to initiate treatment [42]. Timed voiding, approximately 6 times a day, can help relieve symptoms. For relatively large amounts of residual urine, double voiding is recommended. Fluid intake should be regular during the day and minimized before bedtime. In the presence of urinary urgency, DV, or abnormal defecation dynamics caused by problems with the pelvic floor or sphincter muscle relaxation during elimination, pelvic floor muscle training may be the next step [43]. For this, proper education should be provided to ensure an adequate voiding or defecation position where the feet are supported on a flat surface, with attention to the pelvic musculature to improve the coordination between bladder contraction and pelvic muscle relaxation [20]. A simple behavioral treatment can improve frequency and urgency rates in 50% of children [44]. For children unresponsive to simple urotherapy and those without cystourethrogram- or uroflowmetry-confirmed DV, pharmacotherapy is the treatment of choice.

Management of constipation

There are no standard evaluation and management protocols for constipation. Simple constipation may be treated by increasing hydration, adding high-sorbitol juices (e.g., prune, pear, or apple juice), or increasing the number of vegetables in a child’s normal diet. Avoiding excessive milk consumption is also helpful. Currently, there is no evidence supporting the treatment of constipation with pre/probiotic supplements [14]. If dietary interventions fail, polyethylene glycol (PEG), lactulose, or sorbitol may be administered. PEG may be introduced at an initial dose of 1.5 g/kg/day for 6 days, followed by 0.5–0.7 g/kg/day after 24 days.

Pelvic floor muscle retraining and biofeedback

Treatment-refractory OAB in children can be addressed using second-line approaches, such as biofeedback, transcutaneous electrical nerve stimulation, and botulinum toxin. In a study involving 24 children with standard urotherapy- and antimuscarinic therapy-resistant OAB, Pekbay et al. [45] reported that biofeedback-assisted pelvic floor muscle therapy provided symptomatic relief and increased functional bladder capacity.
Nonneurogenic voiding dysfunction in children is a dysmotility disorder related to external sphincter dysfunction. A recent systematic review revealed that biofeedback is effective in alleviating UTI symptoms or constipation. Moreover, biofeedback can improve postvoid residual and electromyography during voiding and has a longer-term effect [46].

Medications

General concept for pharmacologic therapy

Although stepwise therapy, such as behavioral treatment, is important, pharmacotherapy remains the mainstay of treatment. A well-balanced micturition cycle consists of coordinated sympathetic and parasympathetic activities; a reduced parasympathetic tone and an increased sympathetic tone may improve urgency. Muscarinic receptor blockers can be administered to regulate the parasympathetic tone; alpha or beta-agonists may be indicated for sympathetic tone regulation because, during the storage phase, the pontine micturition center is continuously activated and sends descending signals to the hypogastric nerve, which subsequently relaxes the detrusor muscle through beta-adrenoceptor (AR) activation and contracts the internal sphincter through alpha AR activation [10]. However, in practice, alpha agonists are not recommended for OAB because of their systemic effects (especially on vascular smooth muscles). In human bladder smooth muscles, 96% of sympathetic receptors are beta-3 receptors, which represent 97% of the total beta AR mRNA expression in the bladder [18]. Several studies have revealed that beta-3 AR stimulation is associated with increased micturition capacity without aggravating residual volume or contraction power. Targeting beta-3 ARs, therefore, increases the bladder storage volume without affecting the contraction amplitude [4749].

Antimuscarinic agents

Antimuscarinics (also known as anticholinergics) are generally used as the first-line treatment in children who remain symptomatic after urotherapy. Currently, only 2 antimuscarinic agents have received formal approval for use in children (oxybutynin by the U.S. Food and Drug Administration [FDA] and European Medicines Agency [EMA]; tolterodine by the EMA). While several studies have reported significant results with fesoterodine, propiverine [50,51], solifenacin [52,53], and trospium [54], the administration of these drugs, which depends on age and national discipline, has not received official permission.
Although antimuscarinics are the mainstay of medical treatment, their use is associated with significant side effects, such as dry mouth, constipation, and blurred vision, especially at high doses [55]. Many antimuscarinics, including oxybutynin, cross the blood-brain barrier and bind to M2 receptors, negatively affecting cognitive functions in the central nervous system [56]. Adverse events include sedation, confusion, amnesia, and abnormal dreams, which are more common in children [57].

Oxybutynin

Oxybutynin is the most commonly used medication in the pediatric population, despite the absence of randomized clinical trials (RCTs) comparing it with a placebo. However, like adults, many children do not adequately respond to this drug [53]. Oxybutynin may be administered in either immediate-release (IR; 0.3–0.6 mg/kg recommended) or extended-release (ER; 5 mg or 10 mg, up to 20 mg/day) form. Various studies have demonstrated that ER formulations are superior to IR forms, with improved efficacy [5860]. Unfortunately, they need to be swallowed intact. Intravesical instillation is an alternative formulation that allows for higher doses with fewer systemic side effects; however, the application scope is narrow because most children do not use intermittent catheters. Additionally, medical adherence to oxybutynin is not high. In their study, Van Arendonk et al. [61] reported that oxybutynin did not produce significant effects in any more than 20% of patients with daily incontinence; this is the main reason for discontinuing the medication and accounts for approximately 10% of cases [62]. Chapple et al. [63] reported a discontinuation rate with oxybutynin of approximately 32%.

Tolterodine

Tolterodine is also available in 2 formulas (IR and ER), and several studies have reported good efficacy and tolerability in children [64,65]. An RCT confirmed the safety, but not the efficacy, of tolterodine [66]; however, Medhi et al. [67] showed that tolterodine was as effective as oxybutynin and was associated with fewer side effects.

Fesoterodine

Fesoterodine is a long-acting antimuscarinic that can be administered in 4- or 8-mg doses. It is recommended for children weighing >25 kg and is well tolerated by children and adolescents [68].

Solifenacin

Solifenacin is a slow-acting antimuscarinic that is available at 5 or 10 mg. A recent open-label safety extension study by Newgreen et al. [69] confirmed the efficacy of solifenacin, with constipation (12%) and electrocardiogram QT prolongation (9%) as side effects. The same authors also published a phase 3 RCT demonstrating that once-daily oral suspension of solifenacin was superior to a placebo in improving voiding volume parameters [70]. As an extension of this study, the study by Blais et al. [71] revealed that solifenacin was effective and well tolerated in children.

Propiverine

An RCT published in 2009 showed that propiverine significantly improved urinary frequency, urinary incontinence episodes, and mean voided volume [72]. Kim et al. [51] reported an overall response rate of 86.8% in a retrospective review involving 68 children. Moreover, a multicenter observational cohort study demonstrated that propiverine was as effective as oxybutynin, and the tolerability profile of propiverine was more favorable [73].

Beta-3 AR agonists

Beta-3 AR agonists, which were approved for their favorable tolerability profile in pivotal phase 2 and 3 studies, are currently one of the main treatment options for adult patients with OAB. Their use in children with neurogenic detrusor overactivity has only recently been approved by the FDA [50,63,74]. Beta-3 AR agonists increase bladder capacity without changing the bladder pressure or postvoid residual volume by promoting the relaxation of bladder smooth muscles [14]. Compared with antimuscarinics, beta-3 AR agonists show adequate efficacy and have fewer adverse effects (dry mouth 2.0%, constipation 1.6%, headache 2.0%) [74].
The generally accepted mechanism of smooth muscle relaxation comprises downstream adenyl cyclase activation and subsequent cyclic adenosine monophosphate (cAMP) production, followed by Rho-kinase pathway inhibition [75,76]. Additionally, increased cAMP levels lead to protein kinase A activation, which activates large-conductance, calcium-dependent K+ (BK) channels. These activated BK channels hyperpolarize bladder smooth muscles, which increases detrusor stability [77]. Despite the paucity of literature, promising results have recently been reported. In their study, Blais et al. [71] demonstrated that mirabegron is safe and effective in children (median age, 10.1 years) with idiopathic, antimuscarinic-refractory OAB. The results showed that the median bladder capacity (150 → 200 mL), continence rate (89.6%), and quality of life significantly improved without noticeable side effects (P < 0.001).
Having fewer treatment options for pediatric OAB creates significant problems, especially in treating refractory OAB because the next level of therapy is frequently more invasive. In a prospective, off-label study, Morin et al. [78] employed a combination of mirabegron and a standard, maximized antimuscarinic for a mean of 16 months to treat 35 children (median age, 10.3 years) who had an inadequate response or refractory side effects during a 6-month trial of escalating doses of oxybutynin-ER, solifenacin, or fesoterodine. Continence improved in all children, and the median bladder capacity increased from 50% to 74% of that expected for age; 12 remained completely dry, and 2 were withdrawn owing to side effects.
Including the above 2 studies, Kim et al. [79] recently reported the first systematic review (3 prospective and 5 retrospective studies) suggesting the therapeutic role of beta-3 agonists in children: beta-3 agonists significantly improve urodynamic parameters and self-reported outcomes, such as incontinence. After treatment, the pooled effect estimates for maximum cystometric capacity had a mean difference of +99 mL (95% confidence interval, 74.72–122.96).

Invasive Treatment

Botulinum toxin

Clinical trials involving intravesical injections of botulinum toxin A (BoNTA) in children with OAB are currently underway. Despite its off-label use, BoNTA is an alternative for anticholinergic-intolerant patients. BoNTA blocks acetylcholine release at the parasympathetic presynaptic neuromuscular junction, leading to decreased regional muscle contractility and injection site atrophy. Subsequent chemical denervation is a reversible reaction, and inactivation and removal occur over time. The clinical effect appears after approximately 5–7 days, and the maximum effect appears after 4–6 weeks [80]. The paralytic effect varies depending on the muscle type at the injection site; however, it is known that it usually lasts for 3–9 months with no apparent tachyphylaxis [81]. The major disadvantage of BoNTA injections is the need for re-treatment due to temporary chemical denervation, which occurs because synaptic respouting occurs after approximately 6 months. According to a preliminary study, repeated BoNTA injections are safe for children and do not cause additional bladder wall fibrosis [82]. In another histological study, no ultrastructural changes were noted in the bladder muscles after Botox injection [83].
Other studies used varying Botox doses, ranging from 50 to 200 units (up to 200–300 units is commonly used for neurogenic OAB) [8486]. Botox should be used in children over 3 years old at a dose of 5–10 units/kg of body weight [87]. Furthermore, because the effect of Botox is cumulative when treating a child with spasticity, precautions should be taken to determine a history of BoNTA administration at another site within the same period [9]. The full clinical response, defined by complete continence in pediatric patients, was 44%–95% in 2 level 3 studies [84,88]. Moreover, urodynamic improvements (38%–70%) were also reported in 2 laboratory studies [75,76].

Neuromodulation

Over the last 2 decades, neuromodulation has been employed to treat children with nonneurogenic LUTD (Table 1), and several studies have reported that it can significantly improve bladder volume, decrease urgency severity, improve continence, and decrease UTI incidence [8991]. Urodynamic parameters, including bladder compliance, episodes of detrusor overactivity, and volume at first detrusor contraction, also significantly improved [92].
Neuromodulation delivers electrical stimulation that changes existing neural transmission patterns and modulates detrusor activity. It also rebalances excitatory and inhibitory information to put the neural drive into a more neutral state. Although the exact mechanism of action remains unclear, data from many studies reveal that this approach is effective. A meta-analysis has reported that neuromodulation may lead to better partial improvement in children with nonneurogenic OAB; however, a complete response is not guaranteed [93]. The EAU guidelines recommend various neuromodulation modalities only in cases refractory to standard therapy [94]. Despite an initial successful response, a high recurrence rate that warrants long-term follow-up has been reported [95]. Additionally, many children may present with other forms of LUTD as adults [96].

CONCLUSION

OAB is characterized by the inability to properly suppress the urge to urinate. It is a bothersome syndrome that usually begins during childhood and continues into adulthood. Evidence suggests that this condition is primarily related to abnormalities in bladder sensation; therefore, adequate knowledge of neurophysiology may help in OAB management. More studies analyzing the central nervous system as the primary site of voiding dysfunction and the appropriate site for targeted treatment are required. Furthermore, continued research on functional neuroimaging is vital if greater advances are to be made in this field.

NOTES

Funding/Grant Support
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2021R1G1A1014047).
Conflict of Interest
MMO, a member of the Editorial Board of International Neurourology Journal, is the corresponding author of this article. However, she played no role whatsoever in the editorial evaluation of this article or the decision to publish it. No potential conflict of interest relevant to this article was reported.

REFERENCES

1. Bakker E, van Sprundel M, van der Auwera JC, van Gool JD, Wyndaele JJ. Voiding habits and wetting in a population of 4,332 Belgian schoolchildren aged between 10 and 14 years. Scand J Urol Nephrol 2002;36:354-62. crossref
2. Bloom DA, Seeley WW, Ritchey ML, McGuire EJ. Toilet habits and continence in children: an opportunity sampling in search of normal parameters. J Urol 1993;149:1087-90. crossref
3. Sureshkumar P, Craig JC, Roy LP, Knight JF. Daytime urinary incontinence in primary school children: a population-based survey. J Pediatr 2000;137:814-8. PMID: 11113838
crossref pmid
4. Sureshkumar P, Jones M, Cumming R, Craig J. A population based study of 2,856 school-age children with urinary incontinence. J Urol 2009;181:808-15 ; discussion 815–6. PMID: 19110268
crossref pmid
5. Vaz GT, Vasconcelos MM, Oliveira EA, Ferreira AL, Magalhães PG, Silva FM, et al. Prevalence of lower urinary tract symptoms in school-age children. Pediatr Nephrol 2012;27:597-603. PMID: 21969094
crossref pmid pdf
6. Feldman AS, Bauer SB. Diagnosis and management of dysfunctional voiding. Curr Opin Pediatr 2006;18:139-47. PMID: 16601493
crossref pmid
7. Tekgul S, Stein R, Bogaert G, Undre S, Nijman RJM, Quaedackers J, et al. EAU-ESPU guidelines recommendations for daytime lower urinary tract conditions in children. Eur J Pediatr 2020;179:1069-77. PMID: 32472266
crossref pmid pdf
8. Franco I. Pediatric overactive bladder syndrome: pathophysiology and management. Paediatr Drugs 2007;9:379-90. PMID: 18052408
pmid
9. Ramsay S, Bolduc S. Overactive bladder in children. Can Urol Assoc J 2017;11(1–2Suppl1):S74-9. PMID: 28265325
crossref pmid pmc pdf
10. Beckel JM, Holstege G. Neurophysiology of the lower urinary tract. Handb Exp Pharmacol 2011;(202):149-69. PMID: 21290226
crossref pmid
11. Hall JE, Hall ME. Guyton and hall textbook of medical physiology. 14th Ed. Philadelphia (PA): Elsevier Health Sciences; 2020.
12. Michel MC, Chapple CR. Basic mechanisms of urgency: preclinical and clinical evidence. Eur Urol 2009;56:298-307. PMID: 19523751
crossref pmid
13. Bael A, Lax H, de Jong TP, Hoebeke P, Nijman RJ, Sixt R, et al. The relevance of urodynamic studies for Urge syndrome and dysfunctional voiding: a multicenter controlled trial in children. J Urol 2008;180:1486-93 ; discussion 1494–5. PMID: 18710726
crossref pmid
14. Franco I. Overactive bladder in children. Nat Rev Urol 2016;13:520-32. PMID: 27530266
crossref pmid pdf
15. Iguchi N, Malykhina AP, Wilcox DT. Early life voiding dysfunction leads to lower urinary tract dysfunction through alteration of muscarinic and purinergic signaling in the bladder. Am J Physiol Renal Physiol 2018;315:F1320-8. crossref
16. Chung JM, Lee SD, Kang DI, Kwon DD, Kim KS, Kim SY, et al. Prevalence and associated factors of overactive bladder in Korean children 5–13 years old: a nationwide multicenter study. Urology 2009;73:63-7 ; discussion 68–9. PMID: 18829077
crossref pmid
17. Fowler CJ, Griffiths DJ. A decade of functional brain imaging applied to bladder control. Neurourol Urodyn 2010;29:49-55. PMID: 19412958
crossref pmid pdf
18. Yamaguchi O, Chapple CR. Beta3-adrenoceptors in urinary bladder. Neurourol Urodyn 2007;26:752-6. PMID: 17600372
crossref pmid
19. Drake MJ, Fowler CJ, Griffiths D, Mayer E, Paton JF, Birder L. Neural control of the lower urinary and gastrointestinal tracts: supraspinal CNS mechanisms. Neurourol Urodyn 2010;29:119-27. PMID: 20025025
crossref pmid pdf
20. Santos JD, Lopes RI, Koyle MA. Bladder and bowel dysfunction in children: an update on the diagnosis and treatment of a common, but underdiagnosed pediatric problem. Can Urol Assoc J 2017;11(1–2 Suppl 1):S64-72. PMID: 28265323
pmid pmc
21. Franco I, Cagliostro S, Collet-Gardere T. Treatment of lower urinary tract symptoms in children with constipation using tegaserod therapy. Urotoday Int J 2010;3(3): https://doi.org/10.3834/uij.1944-5784.2010.06.17 . crossref
22. Blankstein U, Chen J, Diamant NE, Davis KD. Altered brain structure in irritable bowel syndrome: potential contributions of pre-existing and disease-driven factors. Gastroenterology 2010;138:1783-9. PMID: 20045701
crossref pmid
23. Milsom I, Coyne KS, Nicholson S, Kvasz M, Chen CI, Wein AJ. Global prevalence and economic burden of urgency urinary incontinence: a systematic review. Eur Urol 2014;65:79-95. PMID: 24007713
crossref pmid
24. Logan BA, Correia K, McCarthy J, Slattery MJ. Voiding dysfunction related to adverse childhood experiences and neuropsychiatric disorders. J Pediatr Urol 2014;10:634-8. PMID: 25082714
crossref pmid pmc
25. Griffiths D, Derbyshire S, Stenger A, Resnick N. Brain control of normal and overactive bladder. J Urol 2005;174:1862-7. PMID: 16217325
crossref pmid
26. Griffiths D, Tadic SD. Bladder control, urgency, and urge incontinence: evidence from functional brain imaging. Neurourol Urodyn 2008;27:466-74. crossref
27. Pezzone MA, Liang R, Fraser MO. A model of neural cross-talk and irritation in the pelvis: implications for the overlap of chronic pelvic pain disorders. Gastroenterology 2005;128:1953-64. PMID: 15940629
crossref pmid
28. Ustinova EE, Fraser MO, Pezzone MA. Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical and chemical stimuli: an afferent origin of pelvic organ cross-sensitization. Am J Physiol Renal Physiol 2006;290:F1478-87. PMID: 16403832
crossref pmid
29. Ustinova EE, Gutkin DW, Pezzone MA. Sensitization of pelvic nerve afferents and mast cell infiltration in the urinary bladder following chronic colonic irritation is mediated by neuropeptides. Am J Physiol Renal Physiol 2007;292:F123-30. PMID: 16926445
crossref pmid
30. Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, editors. Campbell-Walsh urology. 10th ed. Philadelphia: Saunders; 2012.
31. Wyndaele M, De Wachter S, De Man J, Minagawa T, Wyndaele JJ, Pelckmans PA, et al. Mechanisms of pelvic organ crosstalk: 1. Peripheral modulation of bladder inhibition by colorectal distention in rats. J Urol 2013;190:765-71. PMID: 23524199
crossref pmid
32. Franco I. Functional bladder problems in children: pathophysiology, diagnosis, and treatment. Pediatr Clin North Am 2012;59:783-817. PMID: 22857829
pmid
33. Herz D, Weiser A, Collette T, Reda E, Levitt S, Franco I. Dysfunctional elimination syndrome as an etiology of idiopathic urethritis in childhood. J Urol 2005;173:2132-7. PMID: 15879866
crossref pmid
34. Berger MY, Tabbers MM, Kurver MJ, Boluyt N, Benninga MA. Value of abdominal radiography, colonic transit time, and rectal ultrasound scanning in the diagnosis of idiopathic constipation in children: a systematic review. J Pediatr 2012;161:44-50e1-2. PMID: 22341242
crossref pmid
35. Farhat W, Bägli DJ, Capolicchio G, O’Reilly S, Merguerian PA, Khoury A, et al. The dysfunctional voiding scoring system: quantitative standardization of dysfunctional voiding symptoms in children. J Urol 2000;164(3 Pt 2):1011-5. PMID: 10958730
crossref pmid
36. Akbal C, Genc Y, Burgu B, Ozden E, Tekgul S. Dysfunctional voiding and incontinence scoring system: quantitative evaluation of incontinence symptoms in pediatric population. J Urol 2005;173:969-73. PMID: 15711352
crossref pmid
37. Bower WF, Sit FK, Bluyssen N, Wong EM, Yeung CK. PinQ: a valid, reliable and reproducible quality-of-life measure in children with bladder dysfunction. J Pediatr Urol 2006;2:185-9. PMID: 18947606
crossref pmid
38. Nelson CP, Park JM, Bloom DA, Wan J, Dunn RL, Wei JT. Incontinence Symptom Index-Pediatric: development and initial validation of a urinary incontinence instrument for the older pediatric population. J Urol 2007;178(4 Pt 2):1763-7 ; discussion 1767. crossref
39. Achenbach TM, Ruffle TM. The Child Behavior Checklist and related forms for assessing behavioral/emotional problems and competencies. Pediatr Rev 2000;21:265-71. PMID: 10922023
crossref pmid pdf
40. Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol 1997;32:920-4. PMID: 9299672
crossref pmid
41. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology 2016 Feb 19;S00165085(16)00223-7. doi: 10.1053/j.gastro.2016.02.032. [Epub]. PMID: 27144617
crossref pmid
42. Butler RJ, Redfern EJ, Holland P. Children’s notions about enuresis and the implications for treatment. Scand J Urol Nephrol Suppl 1994;163:39-47. PMID: 7878383
pmid
43. Franco I, Austin P, Bauer S, von Gontard A, Homsy Y. Pediatric incontinence: evaluation and clinical management. Hoboken (NJ): Wiley-Blackwell; 2015.
44. Wiener JS, Scales MT, Hampton J, King LR, Surwit R, Edwards CL. Long-term efficacy of simple behavioral therapy for daytime wetting in children. J Urol 2000;164(3 Pt 1):786-90. PMID: 10953156
crossref pmid
45. Pekbay Y, Ergin O, Topuz B, Sarikaya S, Acar ZZ, Irkilata HC, et al. The effects of pelvic floor muscle therapy on symptoms, voiding, and pelvic floor muscle activity parameters in children with overactive bladder. Neurourol Urodyn 2019;38:1430-42. PMID: 31006136
crossref pmid pdf
46. Qi W, Zhou Y, Zhong M, Lv G, Li R, Wang W, et al. The effect of biofeedback treatment for children with non-neurogenic voiding dysfunction: a systematic review and meta-analysis. Neurourol Urodyn 2022;41:868-83. PMID: 35191548
crossref pmid pdf
47. Andersson KE. Prospective pharmacologic therapies for the overactive bladder. Ther Adv Urol 2009;1:71-83. PMID: 21789056
crossref pmid pmc pdf
48. Leon LA, Hoffman BE, Gardner SD, Laping NJ, Evans C, Lashinger ES, et al. Effects of the beta 3-adrenergic receptor agonist disodium 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316243) on bladder micturition reflex in spontaneously hypertensive rats. J Pharmacol Exp Ther 2008;326:178-85. PMID: 18413856
crossref pmid
49. Tyagi P, Tyagi V. Mirabegron, a β3-adrenoceptor agonist for the potential treatment of urinary frequency, urinary incontinence or urgency associated with overactive bladder. IDrugs 2010;13:713-22. PMID: 20878594
pmid
50. Khullar V, Amarenco G, Angulo JC, Cambronero J, Høye K, Milsom I, et al. Efficacy and tolerability of mirabegron, a β(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial. Eur Urol 2013;63:283-95. PMID: 23182126
crossref pmid
51. Kim WJ, Lee DG, Lee SW, Lee YK, Lee JS, Park KH, et al. Efficacy and safety of propiverine in children with overactive bladder. Korean J Urol 2012;53:275-9. PMID: 22536472
crossref pmid pmc
52. Bolduc S, Moore K, Nadeau G, Lebel S, Lamontagne P, Hamel M. Prospective open label study of solifenacin for overactive bladder in children. J Urol 2010;184(4 Suppl):1668-73. PMID: 20728124
crossref pmid
53. Hoebeke P, De Pooter J, De Caestecker K, Raes A, Dehoorne J, Van Laecke E, et al. Solifenacin for therapy resistant overactive bladder. J Urol 2009;182(4 Suppl):2040-4. PMID: 19695608
crossref pmid
54. Lopez Pereira P, Miguelez C, Caffarati J, Estornell F, Anguera A. Trospium chloride for the treatment of detrusor instability in children. J Urol 2003;170:1978-81. PMID: 14532838
crossref pmid
55. Maman K, Aballea S, Nazir J, Desroziers K, Neine ME, Siddiqui E, et al. Comparative efficacy and safety of medical treatments for the management of overactive bladder: a systematic literature review and mixed treatment comparison. Eur Urol 2014;65:755-65. PMID: 24275310
crossref pmid
56. Kay GG, Abou-Donia MB, Messer WS Jr, Murphy DG, Tsao JW, Ouslander JG. Antimuscarinic drugs for overactive bladder and their potential effects on cognitive function in older patients. J Am Geriatr Soc 2005;53:2195-201. PMID: 16398909
crossref pmid
57. Soliman MG, El-Abd SA, Tawfik AM, Radwan MH, El-Abd AS. Efficacy and safety of mirabegron versus solifenacin as additional therapy for persistent OAB symptoms after tamsulosin monotherapy in men with probable BPO. World J Urol 2021;39:2049-54. PMID: 32869151
crossref pmid pdf
58. Reinberg Y, Crocker J, Wolpert J, Vandersteen D. Therapeutic efficacy of extended release oxybutynin chloride, and immediate release and long acting tolterodine tartrate in children with diurnal urinary incontinence. J Urol 2003;169:317-9. PMID: 12478180
crossref pmid
59. Van Arendonk KJ, Austin JC, Boyt MA, Cooper CS. Frequency of wetting is predictive of response to anticholinergic treatment in children with overactive bladder. Urology 2006;67:1049-53 ; discussion 1053–4. PMID: 16698366
crossref pmid
60. Youdim K, Kogan BA. Preliminary study of the safety and efficacy of extended-release oxybutynin in children. Urology 2002;59:428-32. PMID: 11880086
crossref pmid
61. Van Arendonk KJ, Knudson MJ, Austin JC, Cooper CS. Improved efficacy of extended release oxybutynin in children with persistent daytime urinary incontinence converted from regular oxybutynin. Urology 2006;68:862-5. PMID: 17070368
crossref pmid
62. Nijman R, Hoebeke P. ICS course 3: urinary incontinence in children. International UroGynecological Association 34th Annual Meeting. 2004 Aug 25–27; Paris, France. Burnsville (MN): International UroGynecological Association; 2004.
63. Chapple CR, Kaplan SA, Mitcheson D, Klecka J, Cummings J, Drogendijk T, et al. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a β(3)-adrenoceptor agonist, in overactive bladder. Eur Urol 2013;63:296-305. PMID: 23195283
crossref pmid
64. Bolduc S, Upadhyay J, Payton J, Bägli DJ, McLorie GA, Khoury AE, et al. The use of tolterodine in children after oxybutynin failure. BJU Int 2003;91:398-401. PMID: 12603422
crossref pmid
65. Podnar S, Vodušek DB. Lower urinary tract dysfunction in patients with peripheral nervous system lesions. Handb Clin Neurol 2015;130:203-24. PMID: 26003246
crossref pmid
66. Nijman RJ, Borgstein NG, Ellsworth P, Djurhuus JC. Tolterodine treatment for children with symptoms of urinary urge incontinence suggestive of detrusor overactivity: results from 2 randomized, placebo controlled trials. J Urol 2005;173:1334-9. PMID: 15758796
crossref pmid
67. Medhi B, Mittal N, Bansal D, Prakash A, Sarangi SC, Nirthi B. Comparison of tolterodine with standard treatment in pediatric patients with non-neurogenic dysfunctional voiding/over active bladder: a systematic review. Indian J Physiol Pharmacol 2013;57:343-53. PMID: 24968572
pmid
68. Malhotra B, El-Tahtawy A, Wang EQ, Darekar A, Cossons N, Crook TJ, et al. Dose-escalating study of the pharmacokinetics and tolerability of fesoterodine in children with overactive bladder. J Pediatr Urol 2012;8:336-42. PMID: 22417681
crossref pmid
69. Newgreen D, Bosman B, Hollestein-Havelaar A, Dahler E, Besuyen R, Snijder R, et al. Long-Term Safety and Efficacy of Solifenacin in Children and Adolescents with Overactive Bladder. J Urol 2017;198:928-36. PMID: 28506854
crossref pmid
70. Newgreen D, Bosman B, Hollestein-Havelaar A, Dahler E, Besuyen R, Sawyer W, et al. Solifenacin in children and adolescents with overactive bladder: results of a phase 3 randomised clinical trial. Eur Urol 2017;71:483-90. PMID: 27687820
crossref pmid
71. Blais AS, Nadeau G, Moore K, Genois L, Bolduc S. Prospective pilot study of mirabegron in pediatric patients with overactive bladder. Eur Urol 2016;70:9-13. PMID: 26876327
crossref pmid
72. Marschall-Kehrel D, Feustel C, Persson de Geeter C, Stehr M, Radmayr C, Sillén U, et al. Treatment with propiverine in children suffering from nonneurogenic overactive bladder and urinary incontinence: results of a randomized placebo-controlled phase 3 clinical trial. Eur Urol 2009;55:729-36. PMID: 18502028
crossref pmid
73. Sacco E, Bientinesi R. Mirabegron: a review of recent data and its prospects in the management of overactive bladder. Ther Adv Urol 2012;4:315-24. PMID: 23205058
crossref pmid pmc pdf
74. Nitti VW, Auerbach S, Martin N, Calhoun A, Lee M, Herschorn S. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol 2013;189:1388-95. PMID: 23079373
crossref pmid
75. Frazier EP, Mathy MJ, Peters SL, Michel MC. Does cyclic AMP mediate rat urinary bladder relaxation by isoproterenol? J Pharmacol Exp Ther 2005;313:260-7. PMID: 15576470
crossref pmid
76. Uchida H, Shishido K, Nomiya M, Yamaguchi O. Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via beta-adrenoceptors. Eur J Pharmacol 2005;518:195-202. PMID: 16054622
pmid
77. Kobayashi H, Adachi-Akahane S, Nagao T. Involvement of BK(Ca) channels in the relaxation of detrusor muscle via beta-adrenoceptors. Eur J Pharmacol 2000;404:231-8. PMID: 10980283
pmid
78. Morin F, Blais AS, Nadeau G, Moore K, Genois L, Bolduc S. Dual therapy for refractory overactive bladder in children: a prospective open-label study. J Urol 2017;197:1158-63. PMID: 27914999
crossref pmid
79. Kim JK, De Jesus MJ, Lee MJ, Dos Santos J, Dy JS, Ming JM, et al. β3-Adrenoceptor agonist for the treatment of bladder dysfunction in children: a systematic review and meta-analysis. J Urol 2022;207:524-33. PMID: 34850638
crossref pmid
80. Gamé X, Mouracade P, Chartier-Kastler E, Viehweger E, Moog R, Amarenco G, et al. Botulinum toxin-A (Botox) intradetrusor injections in children with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review. J Pediatr Urol 2009;5:156-64. PMID: 19264554
crossref pmid
81. Riccabona M, Koen M, Schindler M, Goedele B, Pycha A, Lusuardi L, et al. Botulinum-A toxin injection into the detrusor: a safe alternative in the treatment of children with myelomeningocele with detrusor hyperreflexia. J Urol 2004;171(2 Pt 1):845-8 ; discussion 848. PMID: 14713840
crossref pmid
82. Pascali MP, Mosiello G, Boldrini R, Salsano ML, Castelli E, De Gennaro M. Effects of botulinum toxin type a in the bladder wall of children with neurogenic bladder dysfunction: a comparison of histological features before and after injections. J Urol 2011;185(6 Suppl):2552-7. PMID: 21527192
crossref pmid
83. Figueroa V, Romao R, Pippi Salle JL, Koyle MA, Braga LH, Bägli DJ, et al. Single-center experience with botulinum toxin endoscopic detrusor injection for the treatment of congenital neuropathic bladder in children: effect of dose adjustment, multiple injections, and avoidance of reconstructive procedures. J Pediatr Urol 2014;10:368-73. PMID: 24280272
crossref pmid
84. Hoebeke P, De Caestecker K, Vande Walle J, Dehoorne J, Raes A, Verleyen P, et al. The effect of botulinum-A toxin in incontinent children with therapy resistant overactive detrusor. J Urol 2006;176:328-30 ; discussion 330–1. PMID: 16753434
crossref pmid
85. Lahdes-Vasama TT, Anttila A, Wahl E, Taskinen S. Urodynamic assessment of children treated with botulinum toxin A injections for urge incontinence: a pilot study. Scand J Urol Nephrol 2011;45:397-400. PMID: 21740110
crossref pmid
86. Marte A, Borrelli M, Sabatino MD, Balzo BD, Prezioso M, Pintozzi L, et al. Effectiveness of botulinum-A toxin for the treatment of refractory overactive bladder in children. Eur J Pediatr Surg 2010;20:153-7. PMID: 20112186
crossref pmid
87. Apostolidis A, Dasgupta P, Denys P, Elneil S, Fowler CJ, Giannantoni A, et al. Recommendations on the use of botulinum toxin in the treatment of lower urinary tract disorders and pelvic floor dysfunctions: a European consensus report. Eur Urol 2009;55:100-19. PMID: 18823697
crossref pmid
88. Greer T, Abbott J, Breytenbach W, McGuane D, Barker A, Khosa J, et al. Ten years of experience with intravesical and intrasphincteric onabotulinumtoxinA in children. J Pediatr Urol 2016;12:94e1-6. PMID: 26472538
crossref pmid
89. Bower WF, Moore KH, Adams RD. A pilot study of the home application of transcutaneous neuromodulation in children with urgency or urge incontinence. J Urol 2001;166:2420-2. PMID: 11696802
crossref pmid
90. Hoebeke P, Van Laecke E, Everaert K, Renson C, De Paepe H, Raes A, et al. Transcutaneous neuromodulation for the urge syndrome in children: a pilot study. J Urol 2001;166:2416-9. PMID: 11696801
crossref pmid
91. Roth TJ, Vandersteen DR, Hollatz P, Inman BA, Reinberg YE. Sacral neuromodulation for the dysfunctional elimination syndrome: a single center experience with 20 children. J Urol 2008;180:306-11 discussion 311. PMID: 18499169
crossref pmid
92. De Gennaro M, Capitanucci ML, Mastracci P, Silveri M, Gatti C, Mosiello G. Percutaneous tibial nerve neuromodulation is well tolerated in children and effective for treating refractory vesical dysfunction. J Urol 2004;171:1911-3. PMID: 15076308
crossref pmid
93. Fernandez N, Chua ME, Ming JM, Silangcruz JM, Zu’bi F, Dos Santos J, et al. Neurostimulation therapy for non-neurogenic overactive bladder in children: a meta-analysis. Urology 2017;110:201-7. PMID: 28823638
crossref pmid
94. Groen LA, Hoebeke P, Loret N, Van Praet C, Van Laecke E, Ann R, et al. Sacral neuromodulation with an implantable pulse generator in children with lower urinary tract symptoms: 15-year experience. J Urol 2012;188:1313-7. PMID: 22902022
crossref pmid
95. Beksac AT, Koni A, Bozacı AC, Dogan HS, Tekgul S. Postvoidal residual urine is the most significant non-invasive diagnostic test to predict the treatment outcome in children with non-neurogenic lower urinary tract dysfunction. J Pediatr Urol 2016;12:215.e1-8. PMID: 27233211
crossref pmid
96. Bower WF, Christie D, DeGennaro M, Latthe P, Raes A, Romao RL, et al. The transition of young adults with lifelong urological needs from pediatric to adult services: an international children’s continence society position statement. Neurourol Urodyn 2017;36:811-9. PMID: 27177245
crossref pmid pdf
97. Barroso U Jr, Viterbo W, Bittencourt J, Farias T, Lordêlo P. Posterior tibial nerve stimulation vs parasacral transcutaneous neuromodulation for overactive bladder in children. J Urol 2013;190:673-7. crossref
98. Sillén U, Arwidsson C, Doroszkiewicz M, Antonsson H, Jansson I, Stålklint M, et al. Effects of transcutaneous neuromodulation (TENS) on overactive bladder symptoms in children: a randomized controlled trial. J Pediatr Urol 2014;10:1100-5. PMID: 24881806
crossref pmid
99. Patidar N, Mittal V, Kumar M, Sureka SK, Arora S, Ansari MS. Transcutaneous posterior tibial nerve stimulation in pediatric overactive bladder: a preliminary report. J Pediatr Urol 2015;11:351.e1-6. PMID: 26279104
crossref pmid
100. Boudaoud N, Binet A, Line A, Chaouadi D, Jolly C, Fiquet CF, et al. Management of refractory overactive bladder in children by transcutaneous posterior tibial nerve stimulation: a controlled study. J Pediatr Urol 2015;11:138.e1-10. PMID: 25979217
crossref pmid
101. Quintiliano F, Veiga ML, Moraes M, Cunha C, de Oliveira LF, Lordelo P, et al. Transcutaneous parasacral electrical stimulation vs oxybutynin for the treatment of overactive bladder in children: a randomized clinical trial. J Urol 2015;193(5 Suppl):1749-53. PMID: 25813563
crossref pmid
102. Veiga ML, Costa EV, Portella I, Nacif A, Martinelli Braga AA, Barroso U Jr. Parasacral transcutaneous electrical nerve stimulation for overactive bladder in constipated children: the role of constipation. J Pediatr Urol 2016;12:396.e1-396.e6. PMID: 27426685
crossref pmid
103. Borch L, Hagstroem S, Kamperis K, Siggaard CV, Rittig S. Transcutaneous electrical nerve stimulation combined with oxybutynin is superior to monotherapy in children with urge incontinence: a randomized, placebo controlled study. J Urol 2017;198:430-5. PMID: 28327453
crossref pmid

Fig. 1
Transition of bladder accommodation during filling. Bladder accommodation during filling is a passive process whereby bladder tone and intravesical pressure are maintained as urine accumulates. In patients with overactive bladder, a pathologic urge to urinate occurs in the initial maintenance phase owing to a decreased threshold.
inj-2244228-114f1.jpg
Fig. 2
A preliminary brain neural circuit model during the storage phase. Ascending afferent synapses from the sacral spinal cord reach the PAG. These signals are relayed through the thalamus and hypothalamus to the dorsal ACG on one side and the right insula/lateral PFC on the other side. Subsequently, they move to the medial PFC, which is a decision-making area. When the decision to not urinate is made, chronic PAG inhibition through the long pathway is maintained; as a result, PMC is also suppressed and voiding does not occur. In children with urgency, ACG and insula activity increase while PFC activity decreases, thereby antagonizing chronic PAG inhibition. PAG, periaqueductal gray matter; ACG, anterior cingulate gyrus; PMC, pontine micturition center; PFC, prefrontal cortex.
inj-2244228-114f2.jpg
Table 1
Recent studies on neuromodulation for treating overactive bladder in children
Study ES type No. of patients Treatment protocol Frequency amplitude Treatment period Outcome
Barroso et al. [97] PTNS 22 30 min/session 20 Hz Weekly PTNS: 2 cured
TENS 37 S2–S3: 20 min/session 10 Hz/not stated 3×/wk TENS: 15 cured
Sillén et al. [98] TENS 30 S2–S3: 20 min/session 10 Hz/up to 40 mA 2×/day for 12 wk 19 Improved
Patidar et al. [99] PTNS 40 30 min/session 20 Hz/0–10 mA Weekly for 12 wk 13 Cured, 4 improved
Boudaoud et al. [100] PTNS 11 30 min/session 10 Hz/under 10 mA 12 wk 6 Improved
Quintiliano et al. [101] TENS 13 S2–S3: 20 min/session 10 Hz/not stated 3×/wk 6 Cured
Veiga et al. [102] TENS 69 S2–S4: 20 min/session 10 Hz/not stated 7 wk Cured: 12 after the 10th session, 38 after the 20th session
Borch et al. [103] TENS 21 S2–S3: 2 hr/day 10 Hz/up to 40 mA 10 wk 4 Improved

ES, electrical stimulation; PTNS, percutaneous tibial nerve stimulation; TENS, transcutaneous electrical nerve stimulation; S, sacral level.

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