**6. Treatment of DV**

febrile UTI, thickened bladder wall on ultrasound, children older than 5 years with day and

nighttime incontinence, or children at puberty with persistent enuresis.

98 Recent Advances in the Field of Urinary Tract Infections

**Figure 2.** A 6-year old female child with spinning top urethra and right grade 4 VUR on VCUG.

pattern, or elevated residual urine.

In patients with suspicion of anatomical abnormalities of the lower urinary tract, a diagnos‐ tic cystoscopy may be performed. Routine diagnostic cystoscopy is not recommended [52]. Urodynamic evaluation remains an uncomfortable test for children. Cooperation of the child and the narrow size of the urethra are the major hurdles. A relaxed child-friendly environment and patience on the part of the technician are paramount. Full urodynamic studies are considered invasive and should be reserved for children with neurogenic bladder dysfunction, severe DV, myogenic failure, or symptoms that do not improve with therapy [8, 52]. Urodynamic criteria for DV include too large or small bladder ca‐ pacity, poor bladder compliance, detrusor overactivity or premature contractions, an un‐ sustained voiding contraction, excessive voiding pressure, an intermittent uroflow Urotherapy is the nonsurgical, nonpharmacologic treatment of lower urinary tract function and can be defined as a bladder re-education or rehabilitation program aiming at correction of filling and voiding difficulties. Standard urotherapy is a combination of informing the child and the family about the normal lower urinary tract function and what is abnormal in the patient's voiding and correcting the abnormal voiding habits, lifestyle with regard to flu‐ id intake and diet.

In the setting of discomfort with voiding or dysuria, all efforts should be made to eliminate any dietary irritants, such as caffeine, carbonated beverages, citrus juices, and chocolate. Furthermore, skin care should be initiated in children with eroded or irritated perineal areas from incontinence.

Education emphasizing timed voiding, fluid management, and pelvic floor exercises are key components of the initial management for DV. In addition, education concerning proper posture during voiding should be emphasized to minimize abdominal musculature strain‐ ing. Proper sitting technique with buttock and foot support and comfortable hip position is necessary to enable voiding without recruitment of the abdominal muscles [53, 54]. Hygiene education is also important to limit local skin inflammation that may contribute to holding maneuvers and DV. In this way, coordinated voiding with a relaxed pelvic floor can be fa‐ cilitated at the initiation of management.

Treatment of constipation is also important component of the initial management for DV [55]. Fecal impaction must be managed prior to maintenance therapy. For this purpose laxa‐ tives, stool softeners, and enemas is recommended. Maintenance with balanced diet, fibre supplementation, and oral medications such as mineral oil, polyethylene glycol and lactu‐ lose are recommended to maintain a goal of one bulky bowel movement a day. Treatment of constipation alone has been shown to resolve lower urinary tract abnormalities. Enuresis re‐ solved in 63% and daytime incontinence in 89% of patients presenting with constipation and incontinence in one study [56]. In the same study, resolution of constipation also resolved recurrent UTIs.

Biofeedback therapy is the next line of treatment after conservative approaches have been initiated. Biofeedback is a specific treatment modality that aims to retrain the patient's void‐ ing with the assistance of a computer game. Biofeedback has been used in children as young as four years of age [57]. There is no standard protocol for the correct teaching of biofeed‐ back, but in general there are 2 methods. Real-time uroflowmetry allows the patient to view the urine flow rate that in turn can be used to teach the child to relax his/her pelvic floor musculature with voiding. This method is recommended in children with pelvic floor hy‐ peractivity and no OAB symptoms. Sphincter or pelvic floor electromyography can also be used to teach patients how to voluntarily control their pelvic floor musculature during void‐ ing and thus reduce or prevent detrusor-sphincter incoordination. The advantage in using this method lies in its ability to teach a guarding reflex in addition to the relaxation of the pelvic floor during voiding.

Improvement in incontinence, UTIs, VUR, and constipation with biofeedback therapy is well documented in the literature. Upwards of 80% children will experience improvement marked by a reduction in incontinence and recurrent urinary infection [58] (Figure 3). Fac‐ tors that have been found to improve efficacy of biofeedback include compliance, normal bladder capacity, number of sessions, and use of animation. Independent risk factors to pre‐ dict failure identified by Herndon and colleagues are small bladder capacity and compliance to therapy [40]. Results appear durable at three years and the treatment also seems to help those children in whom urotherapy has failed [59]. The inclusion of biofeedback in urothera‐ py is more likely to lead to an improvement in residual urine [60].

ing with a large post-void residual urine volume. It proved to be well tolerated and allowed patients to rapidly attain continence and eliminate recurrent UTI by achieving more effec‐

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Alpha-adrenergic blockade of receptors at the bladder neck and urethra results in relaxation of smooth muscle and theoretically enables more complete bladder emptying. Although the results have been somewhat mixed, several studies have shown efficacy in reducing subjec‐ tive symptoms and improving objective urinary parameters in children with DV and in‐ creased PVR [64, 65]. Dramatic improvement in flow, initiation of voiding, and PVR was documented in one study by Donohoe and colleagues [66]. All children that met the criteria of primary bladder neck dysfunction (low flow rate, low EMG activity, and delayed initia‐ tion of voiding) improved with alpha-blocker therapy and those that discontinued therapy

The transurethral injection of botulinum toxin into the striated urethral sphincter has been beneficial in spinal cord injury patients with detrusor sphincter dyssynergia [67]. Several small studies have demonstrated improvement [68-70]. Botulinum toxin has also been pro‐ posed as a potentially new treatment regimen to improve bladder emptying for children with DV who have failed standard therapy. Petronijevic et al examined the role of combined the injection of botulinum toxin-A (BTX-A) and biofeedback in the management of the fe‐ male children with DV who were refractory to standard therapy, and analyzed their clinical outcomes. The dose of 500 units of BTX-A was diluted in 2.5 ml saline and injected transper‐ ineally around the urethral meatus at the 3, 6, 9 and 12 o'clock positions, 1 to 2 cm deep into the external urinary sphincter. After treatment the mean voided volume increased while post-void residual urine volume decreased significantly. Significant differences in other uro‐ flowmetry parameters were not found [71]. In another study, Radojicic et al. investigated the results of BTX-A into the urethral sphincter and/or pelvic floor muscle injection combined with behavioural and biofeedback therapy in children with DV resistant to previous treat‐ ments, including behavioural, biofeedback and alpha-blockers in 8 boys and 12 girls. The dose of 100 IU BTX-A was diluted in 4 ml saline and injected by a transperineal 21 or 23 gauge needle in the pelvic floor, including the external sphincter. Six months after treatment residual urine decreased significantly in 17 of 20 patients. Nine patients re-established a nor‐ mal voiding curve and 8 showed improvement. Three did not manifest any significant im‐ provement [72]. The limitations of the studies advocating the use of botulinum toxin are

Sacral neuromodulation has been successful in children with refractory DV, but the invasive‐ ness of this modality has limited its use in children without neurologic deficits [73]. Its feasibili‐ ty and efficacy has been well demonstrated [74]. Storage symptoms resolve in about threefourths of children [74]. The response of DV to neuromodulation with the Interstim neuromodulation device was modest. In a single centre study, urinary incontinence, urgency and frequency, nocturnal enuresis and constipation were improved or resolved in 88%, 69%, 89%, 69% and 71% of the patients, respectively [74]. In a multi-institutional study, about 60% of children with voiding difficulty had some benefit [75]. Neuromodulation offers the additional incentive of a potential improvement in constipation and irritable bowel symptoms [74, 76].

small sample size, lack of standard dosing, and nonrandomization.

tive bladder emptying.

returned to baseline symptoms.

For patients who fail to respond to the above conservative measures, medical therapy is of‐ ten helpful. Anticholinergic agents serve to decrease detrusor overactivity and increase functional bladder capacity in patients with urge syndrome or a detrusor overactivity. Anti‐ cholinergics have been shown to provide effective long-term management of detrusor over‐ activity and may also contribute to a quicker resolution of VUR in the setting of DV [61, 62].

**Figure 3.** The results of the biofeedback after 4 sessions of treatment in the same child; the appearance of ure‐ thra normalized, right grade 4 VUR disappeared on VCUG, and flow curve and EMG activity became normal on Uroflow-EMG.

For patients with small bladder capacity and low PVR in which DV did not improve with 3 sessions of biofeedback, oxybutynin is effective. For children with small capacity bladders and high PVR, a full biofeedback session is often necessary to isolate pelvic floor muscles and lower PVR before initiation of anticholinergics. About 87% of these patients with smallcapacity bladders who do not improve with biofeedback will improve with the addition of anticholinergics [40].

Clean intermittent catheterization (CIC) has been shown to be useful in children with high PVR volumes or myogenic failure that do not improve with standard therapy. This thera‐ peutic approach has become routine in many patients with DV of various aetiologies. Pohl et al. [63] described their experience with using CIC in the treatment of dysfunctional void‐ ing with a large post-void residual urine volume. It proved to be well tolerated and allowed patients to rapidly attain continence and eliminate recurrent UTI by achieving more effec‐ tive bladder emptying.

Improvement in incontinence, UTIs, VUR, and constipation with biofeedback therapy is well documented in the literature. Upwards of 80% children will experience improvement marked by a reduction in incontinence and recurrent urinary infection [58] (Figure 3). Fac‐ tors that have been found to improve efficacy of biofeedback include compliance, normal bladder capacity, number of sessions, and use of animation. Independent risk factors to pre‐ dict failure identified by Herndon and colleagues are small bladder capacity and compliance to therapy [40]. Results appear durable at three years and the treatment also seems to help those children in whom urotherapy has failed [59]. The inclusion of biofeedback in urothera‐

For patients who fail to respond to the above conservative measures, medical therapy is of‐ ten helpful. Anticholinergic agents serve to decrease detrusor overactivity and increase functional bladder capacity in patients with urge syndrome or a detrusor overactivity. Anti‐ cholinergics have been shown to provide effective long-term management of detrusor over‐ activity and may also contribute to a quicker resolution of VUR in the setting of DV [61, 62].

**Figure 3.** The results of the biofeedback after 4 sessions of treatment in the same child; the appearance of ure‐ thra normalized, right grade 4 VUR disappeared on VCUG, and flow curve and EMG activity became normal on

For patients with small bladder capacity and low PVR in which DV did not improve with 3 sessions of biofeedback, oxybutynin is effective. For children with small capacity bladders and high PVR, a full biofeedback session is often necessary to isolate pelvic floor muscles and lower PVR before initiation of anticholinergics. About 87% of these patients with smallcapacity bladders who do not improve with biofeedback will improve with the addition of

Clean intermittent catheterization (CIC) has been shown to be useful in children with high PVR volumes or myogenic failure that do not improve with standard therapy. This thera‐ peutic approach has become routine in many patients with DV of various aetiologies. Pohl et al. [63] described their experience with using CIC in the treatment of dysfunctional void‐

Uroflow-EMG.

anticholinergics [40].

py is more likely to lead to an improvement in residual urine [60].

100 Recent Advances in the Field of Urinary Tract Infections

Alpha-adrenergic blockade of receptors at the bladder neck and urethra results in relaxation of smooth muscle and theoretically enables more complete bladder emptying. Although the results have been somewhat mixed, several studies have shown efficacy in reducing subjec‐ tive symptoms and improving objective urinary parameters in children with DV and in‐ creased PVR [64, 65]. Dramatic improvement in flow, initiation of voiding, and PVR was documented in one study by Donohoe and colleagues [66]. All children that met the criteria of primary bladder neck dysfunction (low flow rate, low EMG activity, and delayed initia‐ tion of voiding) improved with alpha-blocker therapy and those that discontinued therapy returned to baseline symptoms.

The transurethral injection of botulinum toxin into the striated urethral sphincter has been beneficial in spinal cord injury patients with detrusor sphincter dyssynergia [67]. Several small studies have demonstrated improvement [68-70]. Botulinum toxin has also been pro‐ posed as a potentially new treatment regimen to improve bladder emptying for children with DV who have failed standard therapy. Petronijevic et al examined the role of combined the injection of botulinum toxin-A (BTX-A) and biofeedback in the management of the fe‐ male children with DV who were refractory to standard therapy, and analyzed their clinical outcomes. The dose of 500 units of BTX-A was diluted in 2.5 ml saline and injected transper‐ ineally around the urethral meatus at the 3, 6, 9 and 12 o'clock positions, 1 to 2 cm deep into the external urinary sphincter. After treatment the mean voided volume increased while post-void residual urine volume decreased significantly. Significant differences in other uro‐ flowmetry parameters were not found [71]. In another study, Radojicic et al. investigated the results of BTX-A into the urethral sphincter and/or pelvic floor muscle injection combined with behavioural and biofeedback therapy in children with DV resistant to previous treat‐ ments, including behavioural, biofeedback and alpha-blockers in 8 boys and 12 girls. The dose of 100 IU BTX-A was diluted in 4 ml saline and injected by a transperineal 21 or 23 gauge needle in the pelvic floor, including the external sphincter. Six months after treatment residual urine decreased significantly in 17 of 20 patients. Nine patients re-established a nor‐ mal voiding curve and 8 showed improvement. Three did not manifest any significant im‐ provement [72]. The limitations of the studies advocating the use of botulinum toxin are small sample size, lack of standard dosing, and nonrandomization.

Sacral neuromodulation has been successful in children with refractory DV, but the invasive‐ ness of this modality has limited its use in children without neurologic deficits [73]. Its feasibili‐ ty and efficacy has been well demonstrated [74]. Storage symptoms resolve in about threefourths of children [74]. The response of DV to neuromodulation with the Interstim neuromodulation device was modest. In a single centre study, urinary incontinence, urgency and frequency, nocturnal enuresis and constipation were improved or resolved in 88%, 69%, 89%, 69% and 71% of the patients, respectively [74]. In a multi-institutional study, about 60% of children with voiding difficulty had some benefit [75]. Neuromodulation offers the additional incentive of a potential improvement in constipation and irritable bowel symptoms [74, 76].

Less invasive neuromodulatory devices such as tibial nerve stimulation and transcutaneous electrical nerve stimulation (TENS) have been proposed as treatment modalities. Capitanuc‐ ci et al. evaluated the efficacy of percutaneous tibial nerve stimulation for different types of paediatric LUTD. A total of 14 children with idiopathic OAB, 14 with DV, 5 with underac‐ tive bladder, 4 with underactive valve bladder and 7 with neurogenic bladder resistant to conventional therapy underwent percutaneous tibial nerve stimulation weekly for 30 min on a weekly schedule for 12 weeks. Patients with DV were significantly more likely to bene‐ fit as compared to those with OAB at rates of up to 100 % [77]. TENS has had success in the treatment of OAB syndrome when compared with placebo in one prospective trial [78]. The use of neuromodulation as treatment modality in refractory LUTD is promising, but larger prospective trials will be necessary to solidify its role as a treatment modality.

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