In PBS, the bladder is thick walled and there is a large urachal remnant that gives it an hourglass appearance (Fig. 13.3). Histologically, the bladder demonstrates an altered connective tissue to smooth muscle ratio. There is smooth muscle hypertrophy, but the majority of the bladder thickness is due to fibrocytes and collagen. There is no abnormality in the distribution of ganglion cells. Classically, these bladders store urine well, and the urodynamic curve is shifted to the right with a range of voiding pressures noted. In less severe cases, there may be normal bladder pressures, and on the other end of the spectrum, there can be complete DUA.

There is no medical treatment for the DUA in PBS, and surgical intervention for the megacystis involves reduction cystoplasty, which was thought to lead to improved bladder emptying. Initially, it does lead to some improvements, but there appears to be no benefit between those that have undergone reduction cystoplasties and those that have not (Bukowski and Perlmutter 1994). Given these findings, reduction cystoplasty has fallen out of favor in these children. Most are relegated to emptying either by abdominal straining or intermittent catheterization when DUA is present.

In imperforate anus and cloacal anomalies, it was thought for many years that DUA was a result of surgical intervention and that it did not exist prior to surgical repair. After the posterior sagittal approach was popularized, preoperative testing was instituted since it was felt that the approach would not lead to the development of a neurogenic bladder. Much to the astonishment of investigators, it was found that the males with high imperforate anus have a high rate of neurogenic detrusor abnormalities that approaches 80 % preoperatively, and postoperatively, that number could be higher depending on the procedure performed.

In the case of the cloacal anomalies, some patients have detrusor underactivity prior to repair, and others seem to develop it after surgical correction (Camanni et al. 2009; Matsui et al. 2009). In these two studies, underactivity postoperatively was present in almost all patients who underwent total urogenital mobilization. This does not appear to be as prevalent in patients undergoing partial urogenital mobilization. We see a corollary with adults who undergo pelvic surgical dissection for an abdominal perineal pull through or extensive dissection between the bladder and the uterus, and these bladders are affected by the damage to the pelvic plexus, which leads to iatrogenic underactivity. Unfortunately, many of these patients probably have abnormal development of the pelvic plexus or sacral nerve roots and/or spinal cord as seen in the classic Vater syndrome. If we add on the potential for injury from extensive mobilization of the bladder, we have a high rate of DUA in these patients with imperforate anus and cloacal anomalies.

The scenario that is most commonly encountered is the child with DUA due to functional voiding problems. As previously mentioned, it makes up about 4–9 % of the children with lower urinary tract problems seen in large practices that care for these children. Many will present with urgency and urge incontinence. It is not unusual that they also present with recurrent urinary tract infections due to incomplete emptying and stasis. What is noteworthy is that some will have tower flows consistent with high Qmax and then not empty all the way leaving behind large residual urine. In this scenario, there may be a shortening of the effective contraction time of the void resulting in incomplete emptying. In some cases, we may see external sphincter dyssynergia along with evidence of bladder neck dysfunction or isolated bladder neck dysfunction. On VCUG and videourodynamics, we can see delay in opening of the bladder neck and then a narrow and contracted prostatic urethra and external sphincter in some of these children. In this scenario, there is a loss of energy during the contraction that cannot be recovered, and this leads to incomplete emptying and eventual muscle hypertrophy of the bladder. The detrusor contraction along with abdominal straining can lead to these tower curves and therefore give the impression of good voiding pressures even though DUA can exist.

The other pattern that is not unusual is the patient with the plateau flow curve and low Qmax, which is what we would think is most synonymous with these patients that have DUA. In this scenario, the detrusor is not contracting at its full potential and leading to the delay in emptying and usually incomplete emptying. It is also possible that the bladder neck fails to adequately open, along with some degree of detrusor hypocontractility in some patients. We have seen this scenario in some patients with associated autonomic dysfunction. Again there is very little data on these patients with DUA since they make up the minority of the patients that have urodynamics, and recently, there has been a move to refrain from doing urodynamics in children. Moving forward we may have even less data available to define this entity.

It is not uncommon that in cases where the bladder neck is involved, we have seen a large number of patients present with evidence of autonomic dysfunction complaining of dizziness on standing, and in a subgroup that was tested with tilt table testing, we saw clear evidence of autonomic dysfunction. This dysfunction can be affecting the micturition reflexes at Onuf’s nucleus where serotonergic input is responsible for the relaxation of the sphincter. These pathways emanate from the frontal lobes in the anterior cingulate gyrus and the prefrontal cortex, and they are long uninterrupted serotonergic pathways. It is conceivable that in this subset of patients, there could be some form of autonomic dysregulation possibly due to frontal lobe dysfunction. We have some data that points to serotonin being involved in this process from a series of patients that had a history of OAB and elevated PVRs who responded to 5-HT4 agonists (Franco et al. 2010). In the vast majority of patients that exhibit the aforementioned patterns, we can improve emptying by reducing outlet resistance either by correcting the EDSD and/or the internal sphincter dyssynergia (IDSD). In some instances, correction of constipation is all that is necessary to obtain a complete resolution of symptoms.

Glassberg’s group (Van Batavia et al. 2014) describes a subset that engages in voiding postponement volitionally but does not exhibit DUA as specifically described by the ICCS guidelines which includes straining to void, fractionated stream, or low detrusor pressure on urodynamics. They term them DUD (detrusor underutilization disorder). They claim that these patients do not have detrusor underactivity on urodynamics and the majority exhibited normal bell curve patterns. These patients responded well to conventional urotherapy measures. Therefore, we should be weary of the criteria of large bladder capacity and infrequent voiding as a primary definer of DUA in children.

A viral illness that can affect the motor tracts and lead to detrusor areflexia with an intact sensation is the poliomyelitis. However, certain group A and B Coxsackie viruses (especially A7), several echoviruses, and enterovirus type 71 may produce similar findings, and typically these will be temporary. West Nile virus infection can also cause an acute flaccid paralysis that is clinically indistinguishable from paralytic poliomyelitis due to polioviruses.

Lyme’s disease can also present with micturition problems via two mechanisms. The first is direct invasion of the organism into the bladder, and the second is related to neuroborreliosis, leading to meningoencephalopathy, transverse myelitis, myeloradiculitis, and demyelinating lesions of the spinal cord. Micturition disorders can appear in diverse forms such as detrusor hyperreflexia, detrusor-sphincter dyssynergia, and detrusor areflexia (Chancellor et al. 1993). One out of four Lyme encephalomyelitis patients can present with urinary dysfunction (Ackermann et al. 1988).

Vitamin B12 deficiency causes posterior long tract disease by demyelination of the lateral and dorsal (posterior) spinal columns as well as peripheral nerves leading to loss of proprioception with signs of upper motor neuron disease such as Babinski’s response. There is a loss of bladder sensation and increased residual urine due to detrusor areflexia. Sphincteric EMG is intact since the corticospinal tracts are not involved. Erectile function will also be affected. These findings will also be seen in neurosyphilis and vitamin E deficiency.

Wolfram syndrome is a syndrome that manifests with diabetes insipidus, diabetes mellitus, optic atrophy, neurosensory deafness, urinary tract dilatation, and bladder dysfunction which will usually result in death in the third to fourth decade of life. The causative gene (WFS1) which encodes the wolframin protein (in the endoplasmic reticulum) has been identified, and a number of loss-of-function mutations have been described. In a publication in 1998, 6 out of 14 patients (42 %) had atonic bladders, and in a more recent publication, 45 % had elevated post-void residual. In our own experience, bladder emptying can be improved in some by improving outlet resistance, but residuals persist due to DUA.

Weber et al. (2011) describe a homozygous loss-of-function mutation of muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) in five brothers with a PBS-like syndrome. CHRM3 encodes the M3 subtype of muscarinic acetylcholine (ACh) receptors. This mutation leads to a megacystis and prune-like abdominal wall defects. Aside from the DUA in the bladder, all of the brothers exhibited dilated pupils that reacted poorly to light and dry mouth. The mother, father, and sister of the boys were all heterozygous for the mutation. Unfortunately, their bladder function was not tested so we do not know if the heterozygous state can lead to some degree of hypocontractility.

Another mutation has been identified in ACTA2, R179H, that causes a syndrome characterized by dysfunction of smooth muscle cells throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation and hypoperistalsis of the gut, and pulmonary hypertension (Milewicz et al. 2010). The urinary and gastrointestinal problems found in these patients are similar to complications of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), an autosomal recessive condition typically lethal shortly after birth. MMHIS is characterized by megacystis and hydronephrosis, microcolon/short bowel with malrotation, and hypoperistalsis. The underlying genetic defect has not been identified, but the overlap of MMIHS with the ACTA2 R179H phenotype suggests a defect of smooth muscle cell contractile function, possibly from recessive or de novo ACTA2 mutations. Interestingly, congenital mydriasis has been reported in a patient with MMIHS.

Certain medications may be capable of producing DUA. Drugs with known anticholinergic activities are at risk for producing DUA. Other drugs not commonly thought of as having negative effects on detrusor activity include nonsteroidal anti-inflammatories (Minami et al. 2007), and its mode of action is on the PGE2 receptors in the bladder. Ketorolac, which is used commonly for its ability to suppress bladder spasms in children who underwent reflux surgery, is an indicator of this groups potential for a relaxing effect on the detrusor.

We have seen children have a marked change in bladder emptying with the introduction of cetirizine, a histamine h1 receptor antagonists. The whole group of h1 receptor antagonists is capable of producing this effect and is something that the clinician needs to be aware of.

Medications that cause constipation can have an indirect effect on the detrusor via rectal dilation. It is known that rectal dilation can inhibit bladder contractions and impair bladder emptying (Godec 1980; Miyazato et al. 2005).