718 incontinence but also will cause secondary damage and dysfunction of both the upper and lower urinary tracts. Key elements in optimal NBSD management are early diagnosis (including NBSD typology) and early (pre- symptomatic) institution of adequate medical treatment. There is indeed growing evidence that management decisions made during infancy, which prevent both renal damage and secondary bladder-wall changes, potentially impact long-term outcomes for renal function and safe urinary continence. After describing the pathophysiology of NBSD and its possible consequences, this paper focuses on diagnosis (including early identification of patients at risk), treat- ment goals, treatment tools, and practical management of NBSD. Historical evolution The management of NBSD in children has undergone major changes over the years. A first milestone was the introduction of clean intermittent catheterization (CIC) in 1972 [1]. CIC (combined with anticholinergics if required) has made “conservative” (medical) management a suc- cessful treatment option, with a good outcome for quality of life and kidney protection. Further important break- throughs were the wider application of urodynamic testing in the evaluation of infants and young children with suspected NBSD [2–4] and the better pathophysiological understanding of the natural history of NBSD in patients with spina bifida. In spina bifida, the natural history of the urinary tract in untreated NBSD is one of progressive deterioration by the age of 3 years in up to 58% of patients [5]. Several reports have shown this deterioration to be directly related to increased intravesical pressure. In 1981, the bladder pressure at which urethral leakage occurred was found to be a useful predictor of unsafe bladder function [2]. The leak-point pressure, as it is now commonly referred to, has become accepted as one of the urodynamic parameters that allows clinicians to differentiate patients with relatively low or high risk for subsequent upper urinary tract deterioration. In 1984, detrusor external sphincter dyssynergia (DSD) was iden- tified as an important factor leading to functional obstruc- tion, and intravesical pressure was recognized as the pathophysiological mechanism of subsequent upper uri- nary tract deterioration [3]. Shortly thereafter, urodynamics in infants and children was shown to allow a functional classification of NBSD that correlated with clinical entities of incontinence and obstruction, an approach that has allowed the concept of individualized and presymptomatic therapy in high-risk patients [6]. Pediatr Nephrol (2008) 23:717–725 Pathophysiology of the neurogenic bladder Under normal conditions, the detrusor muscle, bladder neck, and striated external sphincter function as a synergistic unit for adequate storage and complete evacuation of urine. In healthy bladders, the change in bladder-filling pressure between empty and full is normally less than 10–15 cm H2O. Normal voiding pressures for males and females are from 50 to 80 cm H2O and from 40 to 65 cm H2O, respectively [7]. In patients with NBSD, disordered innervation of the detrusor musculature and external sphincter adversely affects bladder function. In recent years, it has become clear that children with this condition can be categorized into high- and low-risk groups for secondary damage from a neurogenic bladder based on intravesical pressure. When the detrusor (filling) pressure exceeds 40 cm H2O, glomerular filtration rate decreases and pyelocaliceal and ureteral drainage deteriorates, leading to obstructive hydronephrosis and/or vesicoureteral reflux [2, 8–10]. Even in the absence of reflux or upper urinary tract dilatation, high intravesical pressure can impair drainage of urine into the bladder. Any pathophysiologic process that causes either intermittent or continuous elevation of bladder pressure above 40 cm H2O places the child at risk for upper urinary tract dysfunction, urinary tract infections, and ultimately renal failure. Intermittent elevation of bladder pressure may occur from detrusor hypertonia, hyperreflexia, or both. Hyperreflexia may cause intermittent elevation of bladder pressure, especially if the external sphincter acts reflexively and tightens rather than relaxes in an attempt to prevent micturition [detrusor sphincter dyssynergia (DSD)]. Over a long period of time, hyperreflexia with pressures greater than 40 cm H2O may result in detrusor decompen- sation (areflexia from myogenic failure) or in detrusor hypertrophy with associated sacculations and subsequent diverticula formation. These pathophysiologic changes affect the elastic and vesicoelastic properties of the bladder and also result in mechanical ureterovesical junction obstruction. Continuous elevation of bladder pressure above 40 cm H2O may occur from a hypertonic detrusor or a hypertrophic small-capacity bladder secondary to outflow obstruction [11]. Bladder outlet obstruction is caused by DSD, or by fibrosis of the external urethral sphincter secondary to partial or complete denervation [3, 12, 13]. Bladder outlet obstruction will lead to elevated (pathologic) voiding pressures, which will contribute to either detrusor decompensation or hypertrophy. Finally, recurrent urinary tract infections due to bladder residue may aggravate damage to the neurogenic bladder through processes of transmural inflammation and fibrosis. Together with high intravesical pressures and/or vesicoureteral reflux, these lower urinary tract infections will lead to