**4. Association of LUTD with UTI and VUR**

are often believed to originate from behavioural issues. These behavioural traits may evolve from adverse events that occur around or after the time of toilet training and/or personal stresses [13]. Severe emotional stressors, such as sexual abuse mainly in girls, has been asso‐ ciated with DV, and should be considered in a child, especially a girl, who presents with

Detrusor overactivity as a component of DV may represent a persistence of the normal in‐ fant voiding pattern after toilet training. It may be that a mild delay in the maturation of the central nervous system disrupts the ability of these children to learn true voluntary control over the micturition reflex [5, 14]. An alternative theory to the development of the urge syn‐ drome hypothesizes that detrusor overactivity is caused by the transient obstruction that oc‐ curs with DV [15]. In support of the belief that the roots of DV may be grounded in behavioural issues or central nervous system developmental delays, an association has been demonstrated between DV and attention deficit hyperactivity disorder (ADHD). Higher rates of enuresis, urinary incontinence, constipation, and other voiding symptoms have been

As a result of studies of DV diagnosed in infancy, a congenital or genetic component to the disorder has also been postulated. Small series of infants with signs and symptoms consistent with NNNB syndromes have been reported [18, 19]. Furthermore, DV has been linked to the Ochoa syndrome, a genetic disorder with an autosomal recessive in‐ heritance pattern. The gene locus at chromosome 10q23-q24 is identified as the defective gene in Ochoa syndrome. It is postulated to be the possible gene locus of the NNNB de‐ scribed by Hinman and Allan [20]. This information casts doubt on the commonly held belief that disturbance of behaviour is the sole cause of NNNB because these findings

At least some patients with DV represent occult neurogenic problems that will manifest provided these patients are followed longitudinally [21]. In all individuals with unex‐ plained severe DV, search for an unidentified neurological lesion must be made. A sub‐ tle neurological insult could present as DV. Such lesions may or may not be detectable with current imaging technologies. Routine magnetic resonance imaging in children with lower urinary tract problems without overt neurological signs and symptoms has a low yield of 7.5% but this may be improved by targeting children with abnormal cutaneous findings [22]. Tethered cord syndrome may be identified in some patients with subtle neurological signs and symptoms. Classical tethered cord has been diagnosed on the ba‐ sis of pathologically elongated conus or conus that lies below the L2 level. However, an‐ ecdotal successful outcomes following surgical division of the filum in children with apparently normally located cords suggest that the cord may sometimes be abnormally stretched without being at an abnormal location [23]. Such subtle lesions might also ex‐ plain the occasional presentation in infancy when the problem has its onset before toilet training has commenced [19]. Surgical division of the filum terminale in such patients is

Another possible indirect evidence for an unidentified neurological lesion in these pa‐ tients is the association of a peculiar facial expression in some children with DV [25].

controversial but may yield improvements in bladder dysfunction [24].

new onset DV and no other identifiable etiologic factor [4, 5].

described in children with ADHD [16, 17].

92 Recent Advances in the Field of Urinary Tract Infections

are present at or near the time of birth.

There is not sufficient reported data on the relationship between the type of LUTD with UTI and VUR. The earliest studies of LUTD mostly dealt with either OAB or DV. This is a some‐ what artificial distinction, as these conditions are often combined and sometimes difficult to separate. For that reasons this association will be presented in LUTD children as a whole.

The association between LUTD and UTI has been established, though the causal relationship is not clear. Recurrent UTI has been shown in any studies to be higher in VUR patients with LUTD than in those without such dysfunction [3, 27, 28]. It has been demonstrated that ade‐ quate management of LUTD not only decreases the rate of UTI but also increases resolution of the VUR [27, 29]. Traditionally, recurrent UTI and pyelonephritis have been recognized as potential causes of permanent renal damage [30]. Current opinion is that VUR alone is not sufficient to cause UTI or renal damage. Holland et al. reported that girls with primary VUR followed up for 10 years, with no recurrent UTI, did not develop renal scars [31]. Linshaw showed that VUR does not threaten the kidney as long as UTI is promptly treated [32]. The results of these studies suggest that the association between VUR and UTI is necessary for renal damage to occur, mainly in situations of low detrusor pressure. However, VUR may predispose invasion of the renal parenchyma by bacteria. It has been reported that LUTD is an important risk factor for VUR and renal damage [33]. In addition, current studies have showed that increased intravesical pressure associated with LUTD is a primary factor for in‐ ducing reflux and renal damage [12, 34]. In patients who had UTI the presence of reflux in‐ creased the rate of renal damage [12].

VUR in LUTD is theorized to be not the result of a short mucosal tunnel, but to be the consequence of the high filling and voiding pressures. In patients with LUTD, uninhibit‐ ed detrusor contractions and voluntary constriction of the sphincter, causing a functional obstruction, increase the intravesical pressure. Increased intravesical pressure can pro‐ mote VUR through a possible marginal competence in the valve mechanism [34, 35]. Re‐ cent studies have shown that the prevalence of VUR among children with idiopathic LUTD is between 14% and 46% [11, 12]. Some reports have emphasized bilateral reflux associated with LUTD [12, 36].

pertrophy can lead to an increase in risk factors that predispose the urinary tract to more UTIs and more severe VUR including anatomic bladder abnormalities, constipation, in‐ creased residual urine, higher voiding pressures, and increased urethral bacteria coloniza‐ tion secondary to turbulent flow [41, 42]. Turbulent flow is of particular importance as eddy currents formed by nonlaminar flow leads to reflux of periurethral bacteria to the proximal

Developments Regarding Dysfunctional Voiding and Urinary Tract Infections in Children

http://dx.doi.org/10.5772/53569

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The pelvic floor musculature is closely related to bowel and bladder. Isolated contraction of the pelvic floor musculature was found to lead to spontaneous contraction of the bladder. The cycle of pelvic floor dysfunction contributing to recurrent UTIs and VUR can cause wor‐ sening bladder and bowel symptoms, and increased pelvic floor dysfunction with functional obstruction. Eventually this can lead to a hypertrophied, small-capacity bladder with highpressure voiding that will lead to renal damage. The integral relationship between the pelvic floor activity with UTIs and VUR can be used as a model for developing treatment strategies in affected children to address the cognitive and behavioural aspects of DV and prevent irre‐

Clinical symptoms may vary from mild incontinence to severe disorders with endpoints of irreversible bladder dysfunction with VUR, UTI and resulting nephropathy [8]. Children with DV voiding often present with urinary incontinence both during the day as well as at night. They may have urinary frequency, urgency, urge incontinence or nocturnal enuresis. Such storage symptoms may result from associated detrusor overactivity, urinary infection or reduced bladder capacity consequent to large residual urine and may be aggravated by constipation or behavioural disorders. A distinctive facial expression may be noted in some

Diagnosis relies heavily on a good history and physical examination, but also includes radi‐ ologic and urodynamic evaluation. The history should be directed towards the identification of children with neurologic or anatomic causes of their symptoms, and then distinguish be‐ tween which form or pattern of voiding dysfunction is present. Components of this history include maternal medical issues, perinatal history, developmental milestones, scholastic per‐ formance, behavioural history, specifics around toilet training, patterns of voiding and bow‐ el movements, history of UTI, and family history of voiding dysfunction. The use of a 3-day voiding diary is often helpful to identify the frequency of voiding, voided volumes, and tim‐

Clinical examination must include an assessment of higher mental functions and their ageappropriateness and basic neurological evaluation. On physical examination, attention should be paid to the back and lower spine for cutaneous manifestations of an occult spinal dysraphism and/or sacral agenesis. Neurologic examination should include assessment of lower extremity function, rectal tone, perineal/anal sensation, and intactness of bulbocaver‐

urethra and bladder (milk back phenomenon), causing recurrent infections.

versible damage to the upper urinary tract [40].

**5. Diagnosis and evaluation**

of these patients [8].

ing of incontinent episodes [9].

Van Gool et al. addressed the relationship between DV and reflux for the first time with a retrospective questionnaire in 1992 [37]. The prevalence of uncoordination between the de‐ trusor and urethral sphincter approached 18% and included voiding pattern abnormalities such as urge syndrome, staccato voiding, fractionated and incomplete voiding, and voiding postponement. They also found that, in those children who had spontaneous resolution of their VUR, there was a lower prevalence of DV.

It is important to carefully assess all children with reflux for subtle signs of DV. Chil‐ dren with DV are more likely to have recurrent UTIs, have mild bilateral reflux with less spontaneous resolution, and are less likely to have success with surgical management. The treatment of DV in such children can improve the chances of spontaneous resolution of the reflux and may also reduce recurrent urinary infection. Koff et al. [3] reported on their series of children with VUR, who either resolved spontaneously or were surgically treated, and found that DES was observed in 43% of children with primary VUR and in 77% of a subset of these children who had breakthrough UTI. The presence of DES pat‐ terns was associated with a longer time for spontaneous resolution of low-grade reflux and with unsuccessful surgical outcomes. Of children in the surgically treated group, on‐ ly those with DES developed recurrent and/or contralateral reflux. Children with untreat‐ ed DV undergoing ureteral re-implantation may be at a higher risk for developing recurrent reflux or a new bladder diverticulum [38].

Contrary to these results, Chen and colleagues reported that VUR and UTI are not inde‐ pendent of DV [39]. Their findings are new observations contradicting the previous belief that both UTI and VUR are independently associated with DES. Chen et al. performed a multivariate analysis on 2759 paediatric urology patients, further examining the relationship between DES, VUR, and UTI. Their data demonstrated a higher rate of DES in girls than in boys: 43.7% compared with 23.8%. This group also found that there was no difference in the presence of DES in patients with unilateral and bilateral VUR. Surprisingly, they observed no association of VUR or UTI individually with DES but rather DES was only noted when both of these issues were present. Although this large-scale multivariate analysis is a more statistically powerful study than previous smaller retrospective analyses, the data could be potentially skewed in that all of the patients were recruited from a paediatric urology popu‐ lation, which is not representative of the general paediatric population. Patients with known reflux could potentially be protected from DES by prophylactic antibiotics or continued clin‐ ical follow-up in a specialty setting. On the other hand, it is suggested that there may be two types of reflux: one that is primary or congenital in nature and another that is secondary and in part due to DES and UTI. This study is in line with the neuroplastic theory that postulates that hypertrophy of the bladder and bowel musculature is caused by trophic factors re‐ leased during pelvic floor hyperactivity secondary to central nervous disturbances [40]. Hy‐ pertrophy can lead to an increase in risk factors that predispose the urinary tract to more UTIs and more severe VUR including anatomic bladder abnormalities, constipation, in‐ creased residual urine, higher voiding pressures, and increased urethral bacteria coloniza‐ tion secondary to turbulent flow [41, 42]. Turbulent flow is of particular importance as eddy currents formed by nonlaminar flow leads to reflux of periurethral bacteria to the proximal urethra and bladder (milk back phenomenon), causing recurrent infections.

The pelvic floor musculature is closely related to bowel and bladder. Isolated contraction of the pelvic floor musculature was found to lead to spontaneous contraction of the bladder. The cycle of pelvic floor dysfunction contributing to recurrent UTIs and VUR can cause wor‐ sening bladder and bowel symptoms, and increased pelvic floor dysfunction with functional obstruction. Eventually this can lead to a hypertrophied, small-capacity bladder with highpressure voiding that will lead to renal damage. The integral relationship between the pelvic floor activity with UTIs and VUR can be used as a model for developing treatment strategies in affected children to address the cognitive and behavioural aspects of DV and prevent irre‐ versible damage to the upper urinary tract [40].
