Pediatr Nephrol (2008) 23:717–725 supports its safety also in newborns and infants [33]. Oxybutynin is a tertiary amine with a well-documented therapeutic effect on detrusor hyperactivity, and its effec- tiveness is attributed to a combination of anticholinergic (M3-selective receptor subtype antagonism), antispasmod- ic, local anesthetic and calcium-channel-blocking activity [34]. Several studies have shown its efficacy for decreasing the filling pressure, increasing the capacity of the neuro- genic bladder, and preserving renal function [35–37]. The usual dose regimen of oral oxybutynin is 0.3–0.6 mg/kg per day in three doses. In children with insufficient response or significant systemic side effects to oral oxybutynin, intravesical instil- lation of oxybutynin has been shown to be a highly efficacious, reliable, and well-tolerated therapy for children who would otherwise require surgical therapy [38–43]. Because a solution suitable for intravesical instillation was not available, crushed oxybutynin tablets were used in the earlier trials, with consequent problems of inconvenience and impracticability, and it was the belief of several authors that poor patient compliance could be resolved by an optimized drug preparation [40, 44]. It was subsequently shown that, indeed, eliminating the complex crushing preparation by child or parent makes intravesical oxy- butynin therapy easy to use and acceptable for long-term therapy [41]. The mechanisms underlying the more potent and longer- acting detrusor-suppressive effects of intravesical oxybu- tyinin, as well as its better tolerability, have been investigated by several groups. It was demonstrated that a reduced first-pass metabolism of oxybutynin after intra- vesical instillation, resulting in a reduced generation of the N-desethyl metabolite, may explain the clinically relevant reduction of systemic side effects that characterizes intra- vesical compared with oral oxybutynin therapy [45]. In addition, these pharmacokinetic studies provided first evidence for a direct local rather than a systemic effect of intravesical oxybutynin on detrusor muscle [45]. Further evidence for a local effect of intravesically administered oxybutynin was provided by studies showing local (urothelial) accumulation, suppression of muscarinic recep- tor-mediated detrusor muscle contractions, and blocking of muscarinic receptors in bladder-afferent pathways [46, 47]. In most reports, intravesical oxybutynin is used in dosages between 0.3 and 0.6 mg/kg per day in two or three doses. Given its better tolerability compared with oral treatment, if required, intravesical dosages can be further increased up to doses of 0.9 mg/kg per day [43]. To date, the vast majority (∼ 90%) of patients can be treated successfully with the gold standard treatment of oxybutynin (oral or intravesical) and CIC. Other bladder- relaxant drugs include propiverine (10–15 mg b.i.d. or t.i.d., adult dose), trospium (20 mg b.i.d., adult dose), extended- 721 release oxybutynin, and tolterodine (children 0.25–1 mg b.i.d., adults 1–2 mg b.i.d.). The current experience with compounds other than oxybutynin is still limited in children with neurogenic bladder [48, 49]. Botulinum A toxin injections into the detrusor muscle have been shown to be a potentially valuable approach in the neurogenic overactive bladder [50]. Repeated botulinum A toxin injections (as an alternative for or an additive to anticholinergics) could be considered to postpone or avoid surgical procedures in the small minority of children not responding to standard therapy with CIC and anticholinergics [51]. However, further investigations are required, given remaining concerns about costs and long-term efficacy and safety of prolonged botulinum A toxin administration. Although some authors have advocated alfa-receptor stimulation of the bladder neck, no validated medical treatment is available to enhance the bladder outlet. Medical management of NBSD in clinical practice Optimal management involves first, early diagnosis, in- cluding recognition of high-risk subtypes, and second, proactive institution of adequate treatment. Early proactive treatment of high-pressure dyssynergic lower urinary tracts is important in the long term, not only to preserve renal function [52] but also to prevent poor bladder compliance and the subsequent need for bladder augmentation [35]. Urodynamic assessment is used in newborns and infants to come to a functional classification of NBSD, allowing presymptomatic interventions in the high-risk groups and individualized treatment planning according to the type of dysfunction [6, 29, 53]. In clinical practice, four major subtypes can be used to describe NBSD (Fig. 1): sphincter overactivity combined with detrusor underactivity (type A) or overactivity (type B), and sphincter underactivity combined with detrusor underactivity (type C) or with detrusor overactivity (type D). The easiest type to treat is type A. This bladder type requires early treatment because of urine retention with high filling pressure and continuous leaking. Here, CIC alone is effective and sufficient and will make the bladder safe and infection free, and the patient will be dry in between (social continence). Good care to empty the bladder totally is most important to avoid bladder infections caused by residual urine. Dysfunctional type B will have high filling and high voiding pressures, being very unsafe from birth onward due to DSD. Here, the act of voiding has to be prevented. With oxybutynin, the overactive detrusor can be “pharmacologically converted” to an inactive reservoir (situation similar to type A), which has to be emptied with CIC. In type C, CIC reduces the degree of incontinence and offers much better control over urinary tract infections. To achieve continence, this type will at a