chapter 128 Neuropathic Dysfunction of the Lower Urinary Tract

Dawn Lee MacLellan, MD, FRCSC, Stuart B. Bauer, MD

Many of the clinical problems seen in pediatric urology are the result of neurologic lesions that affect lower urinary tract function. As pediatric urology developed in the latter half of the 20th century, urinary diversion initially was the mainstay of treatment for these children with either intractable incontinence or normal or abnormal upper urinary tracts (Smith, 1972). The advent of clean intermittent catheterization (CIC) in the early 1970s by Lapides and associates (1972), refinements in techniques of urodynamic studies in children (Gierup and Ericsson, 1970; Blaivas et al, 1977; Blaivas, 1979), and the development of surgical modalities in conjunction with CIC to manage incontinence dramatically changed the way this group of children was traditionally managed. Most pediatric urologic centers consider functional assessment of the lower urinary tract as an integral element in the evaluation process and almost if not as important as radiographic visualization in characterizing and managing these abnormal conditions (McGuire et al, 1981; Bauer et al, 1984). The natural outcome of early functional investigation has been the advocacy of proactive or early aggressive management in the children who are at risk for urinary tract deterioration based on specific hostile urodynamic parameters (Perez et al, 1992; Edelstein et al, 1995; Kaufman et al, 1996). This has resulted in (1) a statistically significant decrease in upper urinary tract deterioration, compared with those children followed expectantly in the past, and (2) a dramatic reduction in the need for augmentation cystoplasty (Wu et al, 1997; Kaefer et al, 1999; Bauer, 2000). Furthermore, there is now evidence that molecular changes occur intracellularly when prophylactic treatment is begun as early as possible (Park et al, 1999; Ohnishi et al, 2000). Because urodynamic testing has become such an integral part of any discussion of the subject, the testing process as it applies to children is discussed first and then various neurologic abnormalities that are prevalent in children are elaborated upon. For purposes of minimizing ambiguity the terminology used in this chapter is based on the International Continence Society (ICS) standardization of terminology documents (Abrams et al, 2002, 2003; Neveus, 2006).

Urodynamic Evaluation

Before a urodynamic study is performed it is important for the child and the family to have full knowledge of the procedure. Therefore an explanation of the test is sent to each family before the appointment. Attempts are made to minimize anxiety in children by providing reasons for specific portions of the test and explaining exactly what the child will experience. Premedication is rarely given. Parents are instructed to make sure the child has a bowel movement the night before the study.

In males a topical anesthetic cream is applied to the perineum about 45 minutes before the electromyography (EMG) needle is inserted to record sphincter activity. If possible, the child is instructed to come to the urodynamic suite with a full bladder to obtain an initial representative uroflow. The time of the child’s previous urination (or catheterization) is noted to calculate an average rate of urine production per unit of time. The flowmeter is located in a private bathroom that contains a one-way mirror so that voiding can be viewed unobtrusively. This allows the investigator to see what position the child assumes when voiding and whether a Credé or a Valsalva maneuver is employed by the child to help empty.

Next, the nurse reviews the test and shows the child all the equipment in an attempt to make the patient feel as comfortable as possible. The child is catheterized with either a No. 7 Fr or a No. 11 Fr triple-lumen urodynamic catheter (Cook Urological, Inc, Spencer, IN)—the smaller, the better—after a small amount of liquid lidocaine (Xylocaine) (1%) has been injected into the urethra and held in place for a moment or two. First, the intravesicular pressure is recorded. Then the bladder is drained and the residual urine is carefully measured, yielding a pressure at residual volume (Kaefer et al, 1997). Sometimes it is necessary to aspirate the catheter to get the accurate volume of residual urine, especially if the bladder is underactive (particularly if the child is taking anticholinergic medication) or has been previously augmented and secretes mucus (because it may not drain completely after insertion of a catheter).

A small balloon catheter is passed into the rectum at this time to measure intra-abdominal pressure during the cystometrogram to identify artifacts of motion and monitor increases in abdominal pressure during the filling and emptying phases of the study (Bates et al, 1970; Bauer, 1979).

Before the bladder is filled, a urethral pressure profile is sometimes obtained by infusing saline through the side-hole channel at a rate of 2 mL/min as the catheter is withdrawn at a rate of 2 mm/sec (Yalla et al, 1980). Many centers have eliminated urethral pressure profile measurements in favor of monitoring detrusor leak point pressure (the subtracted detrusor pressure at which the child leaks when the bladder is filled to its functional or maximal capacity). Abdominal leak point pressure is the abdominal pressure at which the child leaks when straining or coughing but that is not as accurate as the detrusor leak point pressure, which is a proportional reflection of outlet resistance (McGuire et al, 1996).

External urethral sphincter EMG is performed using a 24-gauge concentric needle electrode (Diokno et al, 1974; Blaivas et al, 1977b) inserted perineally in boys or paraurethrally in girls and advanced into the skeletal muscle component of the sphincter until individual motor unit action potentials are seen or heard on a standard EMG recorder. Alternatively, perineal electrodes (Maizels and Firlit, 1979) or abdominal patch electrodes (Koff and Kass, 1982) have been used to record the bioelectric activity in the sphincter muscle. Disagreements exist concerning the accuracy of these surface electrode measurements, compared with those obtained with needle electrodes, particularly during voiding. The intactness of sacral spinal cord function is easily measured with needle electrodes by (1) looking at the characteristic waveform of individual motor unit action potentials when the patient is relaxed and the bladder is empty, (2) performing and recording the responses to bulbocavernosus and anal stimulation and to Credé and Valsalva maneuvers, (3) asking the patient to voluntarily contract and relax the external sphincter, and (4) seeing the reaction of the sphincter to filling and emptying of the bladder (Fig. 128–1) (Blaivas et al, 1977a; Blaivas, 1979b).

The rate of bladder filling per minute is selected by first calculating the child’s predicted or known capacity (see Chapter 127) and then dividing the result by 10 in order to fill the bladder slowly. In children with myelodysplasia, the average bladder capacity (in milliliters) fits the following formula: 24.5 × age in years + 62 (Palmer et al, 1997). It has been shown that more rapid filling rates may yield falsely low levels of detrusor compliance and may minimize an overactive detrusor (Turner-Warwick, 1975; Joseph, 1992). The bladder is filled slowly with saline warmed to 37° C to avoid this problem (Chin-Peuckert et al, 2004). When it is important to determine very mild degrees of poor compliance, even slower rates of filling are used to measure its true incidence (Kerr et al, 1994; Yeung et al, 1995; Zermann et al, 1997). Some investigators have recorded pressure at residual volume to measure natural filling pressure as the most accurate means of denoting poor compliance (Kaefer et al, 1997; Walter et al, 1998). During filling, it is helpful to try to divert the child’s attention by asking unrelated questions, reading a story aloud, or showing a movie or cartoon. If the examiner wishes to elicit detrusor overactivity, the child is asked to cough (Mayo, 1978); alternatively, a cold solution may be instilled at a rapid rate. Most urodynamic parameters do not change with a child’s position (sitting vs. supine). However, the sitting position is preferred for the detection of detrusor overactivity and incontinence (Lorenzo et al, 2007).

The study is not considered complete until the child urinates and voiding pressures are measured in those children who urinate on their own. The small size of the urodynamic catheter does not seem to affect micturition pressures adversely, even in very young children. The normal voiding pressure varies from 55 to 80 cm H2O in boys and from 30 to 65 cm H2O in girls (Blaivas et al, 1977b; Blaivas, 1979a; Gierup et al, 1979). Infants tend to have higher voiding pressures than older children. Sometimes it is difficult to get the child to void; patience and time are needed in this situation. Placing a urine collection device under the buttocks of the child when supine or dripping tepid water on the genital area often stimulates the child sufficiently to begin urinating. Once the child has voided, it is important to do the following:

Video-urodynamics has gained popularity since its introduction in 1970 (Bates et al, 1970). Visualization of the bladder and bladder neck during filling and of the urethra during voiding has added a dimension for more accurately integrating all aspects of lower urinary tract function and characterizing an abnormality (Glazier et al, 1997). Incompetency of the bladder neck or pelvic floor or the location of any posterior urethral obstruction can be correlated with pressure measurements and external urethral sphincter EMG activity recorded simultaneously (Zerin et al, 1990). Sometimes, aberrations noted on pressure monitoring of sphincter EMG tracings can be confirmed, enhancing these findings (Passerini-Glazel et al, 1992; Weerasinghe and Malone, 1993). Ambulatory urodynamics has become available and feasible in children with the development of microtransducers mounted on small catheters positioned in the bladder (McInerney et al, 1991; Kulseng-Hanssen and Klevmark, 1996).

Often, because it is appropriate to see the effects of drug administration, studies are repeated under similar circumstances several weeks to months later. This is especially true when one is trying to treat reduced detrusor compliance or overactivity medically. To determine the maximal effect, the usual dose of most drugs is taken 2 to 3 hours before the test is performed a second time. The most commonly used drugs that affect lower urinary tract function are listed in Table 128–1, along with their appropriate dose ranges.

Table 128–1 Drugs That Affect Lower Urinary Tract Function

TYPE Dosage†
Minimum Maximum
Cholinergic    
Bethanechol (Urecholine) 0.7 mg/kg tid 0.8 mg/kg qid
Anticholinergic    
Propantheline (Pro-Banthine) 0.5 mg/kg bid 0.5 mg/kg qid
Oxybutynin (Ditropan) 0.2 mg/kg bid 0.2 mg/kg qid
Glycopyrrolate (Robinul) 0.01 mg/kg bid 0.03 mg/kg tid
Hyoscyamine (Levsin) 0.03 mg/kg bid 0.1 mg/kg tid
Tolterodine (Detrol) 0.01 mg/kg bid 0.04 mg/kg bid
Trospium (Sanctura)* 10 mg/day 20 mg/day
Solifenacin (Vesicare)* 5 mg/day 10 mg/day
Darifenacin (Enablex)* 7.5 mg day 15 mg day
Propiverine (Detrunorm)* 0.1 mg/kg bid 0.4 mg/kg bid
α-Sympathomimetic    
Phenylpropanolamine 2.5 mg/kg tid 2.5 mg/kg qid
Ephedrine 0.5 mg/kg tid 1.0 mg/kg tid
Pseudoephedrine 0.4 mg/kg bid 0.9 mg/kg tid
α-Sympatholytic    
Prazosin (Minipress) 0.05 mg/kg bid 0.1 mg/kg tid
Phenoxybenzamine 0.3 mg/kg bid 0.5 mg/kg tid
β-Sympatholytic    
Propranolol 0.25 mg/kg bid 0.5 mg/kg bid
Smooth Muscle Relaxant    
Flavoxate (Urispas) 3.0 mg/kg bid 3.0 mg/kg tid
Dicyclomine (Bentyl) 0.1 mg/kg tid 0.3 mg/kg tid
Other    
Imipramine (Tofranil) 0.7 mg/kg bid 1.2 mg/kg tid

* Studies evaluating safe dosing in children have not been completed.

† Dosages based on recommendations for a 70-kg person.

Neurospinal Dysraphisms

Myelodysplasia

The most common cause of neurogenic bladder dysfunction in children is abnormal development of the spinal canal and internecine spinal cord. Formation of the spinal cord and vertebral column begins at about the 18th day of gestation. Closure of the canal proceeds in a caudal direction from the cephalad end and is complete by 35 days. The exact mechanism that results in closure and what produces a dysraphic state are yet to be elucidated, but numerous factors have been implicated. The incidence was reported as 1 per 1000 births in the United States (Stein et al, 1982), but there has been a definite decrease in this rate in the past 20 years (Laurence, 1989; Lary and Edmonds, 1996; CDC, 2004; Williams et al, 2005). With the advent of prenatal screening, many affected fetuses are being identified and the pregnancies terminated before 16 weeks of gestation, thereby lowering the number of children born with this disease (Palomaki et al, 1999). The addition of folate supplements to the diet of women of childbearing age has also reduced the incidence of spina bifida worldwide (Committee on Genetics, American Academy of Pediatrics, 1999). The incidence of myelodysplasia (per 1000 live births) in the general population is 1.0, for a mother with one affected child it is 20 to 50, and for a patient with myelodysplasia it is 40 (Scarff and Fronczak, 1981; Stein et al, 1982). Therefore when the disease is already present in a family, the Medical Research Council Vitamin Study Group recommends that women of childbearing age take 4000 µg (4.0 mg) of folic acid per day beginning at least 2 months before the time they plan on becoming pregnant (Committee on Genetics, American Academy of Pediatrics, 1999). There is strong evidence that folate deficiency can lead to a myelodysplastic abnormality de novo; therefore, maternal ingestion of 400 µg of folate per day in all women of childbearing age can reduce the incidence of spina bifida by 50% (Laurence et al, 1981; MRC Vitamin Study Research Group, 1991; Czeizel and Dudas, 1992; Centers for Disease Control and Prevention, 2004). It is now mandatory that enriched grain products be fortified with folic acid (U.S. Food and Drug Administration, 1996). Since these recommendations have been followed worldwide, there has been a reduction in neural tube defects in the United States (Williams et al, 2005) and elsewhere (Botto et al, 2005). In some cases, however, despite increased folic acid intake, women may still give birth to a child with spina bifida owing to antibodies that have developed in response to the increased folate ingestion, thus negating its salutary effect (Rothenberg et al, 2004).

Pathogenesis

Myelodysplasia is an all-inclusive term used to describe the various abnormal conditions of the vertebral column that affect spinal cord function. More specific labels for each abnormality include the following: a meningocele occurs when just the meninges but no neural elements extend beyond the confines of the vertebral canal; in a myelomeningocele, neural tissue, either nerve roots or portions of the spinal cord, has evaginated with the meningocele (Fig. 128–2); the term lipomyelomeningocele denotes that fatty tissue has developed with the cord structures and both are extending with the protruding sac. Myelomeningocele accounts for more than 90% of all open spinal dysraphic states (Stark, 1977). Most spinal defects occur at the level of the lumbar vertebrae, with the sacral, thoracic, and cervical areas, in decreasing order of frequency, less affected (Bauer et al, 1977) (Table 128–2). An overwhelming number of meningoceles are directed posteriorly, but on rare occasions they may protrude anteriorly, particularly in the sacral area. Usually the meningocele is made up of a flimsy covering of transparent tissue, but it may be open and leaking cerebrospinal fluid. For this reason urgent repair is necessary, with sterile precautions being followed in the interval between birth and spinal canal closure. In 85% of affected children there is an associated Arnold-Chiari malformation, in which the cerebellar tonsils have herniated down through the foramen magnum, obstructing the fourth ventricle and preventing the cerebrospinal fluid from entering the subarachnoid space surrounding the brain and spinal cord.

Table 128–2 Spinal Level of Myelomeningocele

LOCATION INCIDENCE (%)
Cervical–high thoracic 2
Low thoracic 5
Lumbar 26
Lumbosacral 47
Sacral 20

In the past several years, several centers in the United States have begun closing the defect in fetuses between 19 and 25 weeks of gestation in an attempt to improve the neurologic defect in these children (Adzick et al, 1998; Bruner et al, 1999; Holzbeierlein et al, 2000). Thus far, this procedure has not altered the incidence of abnormal findings in the lower extremities (Farmer et al, 2003) or on urodynamic assessment in the postnatal period (Koh et al, 2003), but, surprisingly, aqueduct obstruction and, consequently, hydrocephalus has not occurred at birth to the same incidence or extent (Johnson et al, 2003). It is possible that leakage of cerebrospinal fluid from the open spinal column accounts for herniation of the posterior brainstem down the foramen magnum, leading to the development of hydrocephalus.

The neurologic lesion produced by the myelomeningocele can be variable, depending on what neural elements, if any, have everted with the meningocele sac. The bony vertebral level often provides little or no clue to the exact neurologic level or lesion produced. The height of the bony level may differ from the highest extent of the neurologic lesion for one to three vertebrae in either direction (Bauer et al, 1977). Furthermore, there may be differences in function from one side of the body to the other at the same neurologic level and from one neurologic level to the next, owing to asymmetry of the affected neural elements. It is important to remember that no two children have the same neurourologic defect. In addition, in 20% of affected children a vertebral bony or intraspinal abnormality occurs more cephalad than the vertebral defect and meningocele, and this can affect function in those portions of the cord. Children with thoracic or upper lumbar meningoceles often have complete reconstitution of the spine in the sacral area, and these individuals frequently have intact sacral reflex arc function involving the sacral spinal roots (in the authors’ series of patients with high-level lesions, 74% of neonates and 54% of older children were affected thusly) (Pontari et al, 1995). In fact, it is more likely that children with upper thoracic or cervical lesions will have just a meningocele and no myelomeningocele. Children with neurologic deficits at S1 or lower may also manifest a variety of findings on urodynamic testing, ranging from normal function to upper and/or lower motor neuron lesions involving either the bladder and/or the external urethral sphincter (Dator et al, 1992). Upper motor neuron lesions are characterized by an overactive detrusor, exaggerated sacral reflexes, absence of voluntary control over sphincter function, detrusor-sphincter dyssynergia (DSD), and no EMG evidence of denervation potentials in the sphincter (White and Klauber, 1976; Koff and DeRidder, 1977; Guzman et al, 1983; Capitanucci et al, 1997). The bladder tends to be thick walled (or trabeculated) with a closed bladder neck on voiding cystourethrography (VCUG) or ultrasonography. A lower motor neuron lesion is noted when an acontractile detrusor and partial or complete denervation of the external urethral sphincter with diminished or absent sacral reflexes may be seen. In these instances the bladder is usually small and smooth walled with an open bladder neck (Wilmshurst et al, 1999). The presence or absence of the bulbocavernosus reflex is an indicator (although not a foolproof one) of an upper or a lower motor neuron lesion, respectively (Schlussel et al, 1994). Approximately 10% of neonates with myelomeningocele exhibit no abnormality on urodynamic testing (Tarcan et al, 2001). Finally, the differing growth rates of the vertebral bodies and the elongating spinal cord add a dynamic factor in the developing fetus that further confounds the picture (Lais et al, 1993). Twenty-four percent of children with normal lower urinary tract function at birth develop upper motor neuron changes over time (Tarcan et al, 2001). Superimposed on all this is the Arnold-Chiari malformation, which can have a profound effect on the brainstem and pontine mesencephalic center, areas that are involved in control of lower urinary tract function.

Therefore the neurologic lesion produced by this condition influences lower urinary tract function in a variety of ways and cannot be predicted just by looking at the spinal abnormality or the neurologic function of the lower extremities. Even careful assessment of the sacral area may not provide sufficient information to make a concrete inference. As a result, urodynamic evaluation in the neonatal period is now the standard of care at most pediatric centers in the United States, because it not only provides a clear picture of the function of the sacral spinal cord and lower urinary tract but also has predictive value in infants at risk for future urinary tract deterioration and progressive neurologic change (McGuire et al, 1981; Van Gool et al, 1982; Bauer, 1984b; Sidi et al, 1986). The advent of hostility scores and the reliability of urodynamic risk factors have led many clinicians to initiate prophylactic therapy in those neonates considered to be at risk for urinary tract deterioration (Perez et al, 1992). There are some, however, who do not consider urodynamic testing an important factor but rely solely on physical examination and radiologic assessment to direct their decision-making process (Hopps and Kropp, 2003), a concept not shared by many.

Neonatal Assessment

Ideally, it would be best to perform urodynamic testing immediately after the infant is born, but the risk of spinal infection and the urgency for closure have not made this a viable option. It was accomplished in one study, however, and the results showed that 1 in 30 children (3.2%) experienced a change in neurologic status as a result of the spinal canal closure (Kroovand et al, 1990). Therefore, renal ultrasonography and measurement of residual urine are performed as early as possible after birth, either before or immediately after the spinal defect is closed. Urodynamic studies are delayed until it is safe to transport the child to the urodynamic suite and place him or her on the back or side for the test. The initial urodynamic study should be performed within the first 3 months of life. If the infant cannot empty the bladder after a spontaneous void or with a Credé maneuver, CIC is begun even before urodynamic studies are conducted. If the Credé maneuver is effective in emptying the bladder, it is performed on a regular basis instead of using CIC until the lower urinary tract can be fully investigated. The normal bladder capacity in the neonatal period is 10 to 15 mL; therefore, a residual urine volume of less than 5 mL is acceptable. Other tests that should be performed in the neonatal period include a urinalysis and culture, serum creatinine determination, and careful neurologic examination of the lower extremities.

Once the spinal closure has healed sufficiently, a renal ultrasonogram is performed to reassess upper urinary tract architecture. Next, VCUG and urodynamic study are conducted. These studies meet several objectives: they provide baseline information about the radiologic appearance of the upper and lower urinary tracts as well as the condition of the sacral spinal cord and the central nervous system (CNS); they provide information that can be compared with findings on subsequent assessments, so that early signs of deterioration of urinary tract function and drainage, or of progressive neurologic denervation, can be detected; they help to identify infants at risk for urinary tract deterioration as a result of a poorly compliant or overactive detrusor or outflow obstruction from DSD, which predetermines the need to initiate prophylactic measures before any deterioration in upper urinary tract architecture and function actually takes place; and they help the physician to counsel parents about the child’s future bladder and sexual function (McGuire et al, 1981; Bauer et al, 1984; Bauer, 1984a; Sidi et al, 1986; Lais et al, 1993). If an abnormality is detected on renal ultrasonography or vesicoureteral reflux is demonstrated, a dimercaptosuccinic acid (DMSA) renal scan is recommended.

Findings

Fifteen to 20 percent of neonates have an abnormal urinary tract on radiologic examination when first evaluated (Bauer, 1985); 3% have hydroureteronephrosis secondary to spinal shock, probably from the spinal canal closure (Chiaramonte et al, 1986), and 15% have abnormalities that developed in utero as a result of abnormal lower urinary tract function in the form of outlet obstruction (Bauer, 2003).

Urodynamic studies in the neonatal period have shown that 63% of infants have bladder contractions. This is also true for an equivalent number of children with upper lumbar or thoracic lesions in whom the sacral spinal cord is spared, 50% of whom have detrusor overactivity (Pontari et al, 1995). Thirty-seven percent have an acontractile detrusor with compliance during filling that is either good (20%) or poor (17%) in this subgroup (Bauer et al, 1984; Bauer, 2003). EMG assessment of the external urethral sphincter demonstrates an intact sacral reflex arc with no evidence of lower motor neuron denervation in 40% of neonates; partial denervation is seen in 24%; and complete loss of sacral cord function is noted in 36% (Lais et al, 1993; Bauer, 2003).

A combination of bladder contractility and external sphincter activity results in three categories of lower urinary tract dynamics: synergic (26%), dyssynergic with and without poor detrusor compliance (37%), and complete denervation (36%) (Fig. 128–3) (Bauer et al, 1984; Sidi et al, 1986; Bauer, 2003). DSD occurs when the external sphincter fails to decrease or actually increases its activity during a detrusor contraction or a sustained increase in intravesical pressure as the bladder is filled to capacity (Blaivas et al, 1986). Frequently, a poorly compliant bladder with high intravesical pressure occurs in conjunction with a dyssynergic sphincter, resulting in a bladder that empties only at high intravesical pressure (Van Gool et al, 1982; Sidi et al, 1986). Synergy is characterized by complete silencing of the sphincter during a detrusor contraction or when capacity is reached at the end of filling. Voiding pressures are usually within the normal range. Complete denervation is noted when no bioelectric potentials are detectable in the region of the external sphincter at any time during the micturition cycle or in response to sacral stimulation or a Credé maneuver.

The categorization of lower urinary tract function in this way has been extremely useful because it reveals which children are at risk for urinary tract changes, who should be treated prophylactically, who need close surveillance, and who can be monitored at shorter or longer intervals. Within the first 3 years of life, 71% of neonates with DSD had urinary tract deterioration on initial assessment or subsequent studies whereas only 17% of synergic children and 23% of completely denervated individuals developed similar changes (Fig. 128–4). Infants in the synergic group who showed deterioration did so only after they converted to a dyssynergic pattern of sphincter function. Among the infants with complete denervation, the ones who showed deterioration were those who had increased levels of urethral resistance, presumably caused by fibrosis of the skeletal muscle component of the external sphincter. Therefore, it appears that outlet obstruction is a major contributor to the development of urinary tract deterioration in these children (Fig. 128–5). Poor detrusor compliance plays an important role in this regard, especially when outlet resistance exceeds 40 cm H2O (McGuire et al, 1981; Landau et al, 1994; Tanaka et al, 1999). Detrusor compliance seems to be worse in children with high levels of outlet resistance (Ghoniem et al, 1989). Bloom and colleagues (1990) and then Park and associates (2001) noted an improvement in compliance when outlet resistance was reduced after gentle urethral dilation in these children; however, the reasons for this change are unclear, and the long-term effect of this maneuver on ultimate continence and lower urinary tract function remains uncertain.

It may be that detrusor filling pressures need to be looked at in a more critical way to determine whether they are an important factor in upper urinary tract deterioration. Landau and colleagues (1994) developed the concept of low detrusor filling pressure (<30 cm H2O) at specific volumes adjusted for age and not at maximal capacity. Applying this idea, they noted significantly improved sensitivity in predicting upper urinary tract deterioration. The ability to predict accurately which neonates are at risk for urinary tract deterioration prompted the initiation of prophylactic therapy with CIC and anticholinergic drugs (Geranoitis et al, 1988; Kasabian et al, 1992). Long-term success has been achieved in preventing reflux and hydronephrosis and in reducing the need for augmentation cystoplasty, from between 27% and 41% to between 11% and 17% (Edelstein et al, 1995; Wu et al, 1997; Kaefer et al, 1999). Others believe that aggressive observation and prompt intervention yields similar long-term results with less morbidity from catheterization (Teichman et al, 1994), but only time will delineate which avenue of treatment is most efficacious (Tanaka et al, 1999; Hopps and Kropp, 2003).

Management Principles

Because expectant treatment has revealed that infants with outlet obstruction in the form of DSD are at considerable risk for urinary tract deterioration, the idea of treating these children prophylactically has emerged as an important alternative. When CIC is begun in the neonatal period, it is easy for parents to master, even in uncircumcised boys, and for children to accept as they grow (Joseph et al, 1989). Complications such as meatitis, epididymitis, and urethral injury are rarely encountered, and urinary infections occur in fewer than 30% (Kasabian et al, 1992), although asymptomatic bacteriuria can be seen in almost 70% (Schlager et al, 2001).

CIC alone or in combination with anticholinergic agents, when detrusor filling pressures exceed 40 cm H2O and voiding pressures are higher than 80 to 100 cm H2O, resulted in an incidence of urinary tract deterioration of only 8% to 10% (Geranoitis et al, 1988; Kasabian et al, 1992; Edelstein et al, 1995). This represents a significant drop in the occurrence of detrimental changes compared with children observed expectantly (McGuire et al, 1981; Bauer et al, 1984; Sidi et al, 1986; Teichman et al, 1994; Wu et al, 1997). Oxybutynin is administered in a dose of 0.2 to 0.4 mg/kg divided two or three times daily with no apparent side effects. On rare occasions when an overactive or poorly compliant bladder fails to respond to these measures, augmentation cystoplasty may be needed with cutaneous vesicostomy almost never required (Duckett, 1974; Mandell et al, 1981).

Neurologic Findings and Recommendations

The neurologic lesion in myelodysplasia is a dynamic disease process in which changes take place throughout childhood (Epstein, 1982; Reigel, 1983; Venes and Stevens, 1983; Oi et al, 1990), especially in early infancy (Spindel et al, 1987) and later at puberty (Begger et al, 1986), when the linear growth rate accelerates again. When a change is noted on neurologic, orthopedic, or urodynamic assessment, radiologic investigation of the CNS often reveals (1) tethering of the spinal cord (Fig. 128–6), (2) a syringomyelia, a dilation and fluid collection within the spinal cord, (3) increased intracranial pressure due to a shunt malfunction, or (4) partial herniation of the brainstem and cerebellum. Children with completely intact or only partially denervated sacral cord function are particularly vulnerable to progressive changes. Magnetic resonance imaging (MRI) is the test of choice because it reveals anatomic details of the spinal column and CNS (Just et al, 1990). However, it is not a functional study and when used alone it cannot provide exact information about a changing neurologic lesion.

Sequential urodynamic testing on a yearly basis beginning in the neonatal period and continuing until the child is 5 years old provides a means of carefully monitoring these children to detect signs of change, thus offering the hope that early detection and neurosurgical intervention may help to arrest or even reverse a progressive pathologic process. Changes occurring in a group of neonates monitored in this manner involved both the sacral reflex arc and the pontine-sacral reflex interaction (Fig. 128–7) (Lais et al, 1993). Most children who experience such changes tend to do so in the first 3 years of life (Phuong et al, 2002) (Fig. 128–8). Twenty-two of 28 children in whom the neurologic picture became worse underwent a second neurosurgical procedure; 11 of them had a beneficial effect from the surgery and showed improvement in urethral sphincter function (Lais et al, 1993). Infants with only sacral level deficits have a 47% risk of deterioration (Dator et al, 1992). Even children with normal neurourologic function at birth have a 32% risk of developing a tethered spinal cord with the development of DSD with or without detrusor overactivity (Tarcan et al, 2001).

As a result of these developments it is recommended that all infants with myelodysplasia be monitored according to the guidelines set forth in Table 128–3. It is not enough to look at just the radiologic appearance of the urinary tract; scrutiny of the functional status of the lower urinary tract is important as well. In addition to the reasons cited previously, it may be necessary to repeat a urodynamic study if the upper urinary tract dilates secondary to impaired drainage from a poorly compliant detrusor.

Table 128–3 Surveillance in Infants with Myelodysplasia*

SPHINCTER ACTIVITY RECOMMENDED TESTS FREQUENCY
Intact–synergic Postvoid residual volume q 4 mo
  US q 12 mo
  UDS q 12 mo
Intact–dyssynergic† US q 12 mo
  UDS q 12 mo
  VCUG or RNC‡ q 12 mo
Partial denervation Postvoid residual volume q 4 mo
  US q 12 mo
  UDS§ q 12 mo
  VCUG or RNC‡ q 12 mo
Complete denervation Postvoid residual volume q 6 mo
  US q 12 mo

US, renal ultrasonography; UDS, urodynamic study; VCUG, voiding cystourethrography; RNC, radionuclide cystography.

* Until age 5 years.

† Patients receiving intermittent catheterization and anticholinergic agents.

‡ If detrusor hypertonicity or reflux is already present.

§ Depending on degree of denervation.

Beyond the age of 5 years renal ultrasonography every 18 months until puberty and then every 2 years thereafter is recommended. Urodynamic studies are indicated to evaluate the development of new neurologic symptoms, new hydronephrosis, or changes in continence. VCUG should be done if recurrent urinary tract infections are experienced.

Management of Reflux

Vesicoureteral reflux occurs in 3% to 5% of neonates with myelodysplasia, usually in association with poor detrusor compliance, detrusor overactivity, and/or DSD (Flood et al, 1994). It is rare to find reflux in any neonate without these urodynamic findings (Bauer, 1984b; Geranoitis et al, 1988; Edelstein et al, 1995). If left untreated, the incidence of reflux in these infants at risk increases with time until 30% to 40% are afflicted by 5 years of age (Bauer, 1984a; Seki et al, 1999). Prophylactic treatment that lowers detrusor filling and voiding pressures with anticholinergic agents and empties the bladder by means of CIC significantly reduces this rising incidence of reflux (Edelstein et al, 1995).

In children with reflux grades 1 to 3 (International Classification) who void spontaneously or have complete lesions with little or no outlet resistance and empty their bladder completely, management consists solely of prophylaxis with antibiotics to prevent recurrent infection. In children with high-grade reflux (grade 4 or 5), CIC is begun to ensure complete emptying. Children who cannot empty their bladder spontaneously, regardless of the grade of reflux, are treated with CIC to empty the bladder efficiently. Children with poor detrusor compliance with or without hydroureteronephrosis are also started on anticholinergic agents to lower intravesical pressure and ensure adequate upper urinary tract decompression (Flood et al, 1994). When reflux is managed in this manner there has been a dramatic response, with reflux resolving in 30% to 55% of individuals (Kass et al, 1981; Bauer, 1984b; Joseph et al, 1989; Flood et al, 1994; Agarwal et al, 1997; Hopps and Kropp, 2003). Although bacteriuria can be seen in as many as 56% of children on CIC it is not harmful except in the presence of high-grade reflux, because symptomatic urinary infection and renal scarring rarely occur with lesser grades of reflux (Kass et al, 1981; Cohen et al, 1990).

Credé voiding should be avoided in children with reflux, especially those with a reactive external urethral sphincter. In this circumstance, the Credé maneuver results in a reflex response in the external sphincter that increases urethral resistance and raises the pressure needed to expel urine from the bladder (Barbalais et al, 1983) (Fig. 128–9). This has the effect of aggravating the degree of reflux and accentuating its water-hammer effect on the kidneys. Vesicostomy drainage (Duckett, 1974; Mandell et al, 1981) is rarely required today but is reserved for those infants (1) who have such severe reflux that CIC and anticholinergic medication fail to improve upper urinary tract drainage, (2) whose parents cannot adapt to the catheterization program, or (3) who are not good candidates for augmentation cystoplasty (Morrisroe et al, 2005).

The indications for antireflux surgery in this group of children are not very different from those applicable to children with normal bladder function. They include recurrent symptomatic (febrile) urinary infection while receiving adequate antibiotic therapy and appropriate catheterization techniques; persistent hydroureteronephrosis despite effective emptying of the bladder and lowering of intravesical pressure; severe reflux with an anatomic abnormality at the ureterovesical junction; reflux that persists into puberty; and the presence of reflux in any child undergoing surgery to increase bladder outlet resistance. Although some clinicians do not advocate reimplanting ureters in patients with low-grade reflux who are undergoing augmentation cystoplasty to lower intravesical pressure, this concept is not universally accepted (Nasrallah and Aliabadi, 1991).

Jeffs and colleagues (1976) were the first to show that antireflux surgery can be very effective in children with neurogenic bladder dysfunction as long as it is combined with measures to ensure complete bladder emptying. Before this observation was made, the results of ureteral reimplantation were so dismal that most physicians treating these children advocated urinary diversion as a means of managing reflux (Smith, 1972; Cass, 1976). Since the advent of CIC, success rates for antireflux surgery have approached 95% (Kass et al, 1981; Woodard et al, 1981; Bauer et al, 1982; Kaplan and Firlit, 1983). Bilateral surgery for unilateral disease need not be done, because contralateral reflux does not occur postoperatively (Bauer, 1984a). The endoscopic injection of various materials has altered the management of reflux in children with myelomeningocele (Elder et al, 2004; Schlussel, 2004). A recent meta-analysis demonstrated that the success rate of endoscopic treatment is less in children with neurogenic bladder than those with normal bladder function (62% vs. 74%) (Elder et al, 2004). Studies comparing the effectiveness of open surgical to endoscopic management in this population show a significantly greater success rate for traditional open procedures (61% to 72.5% vs. 84.3% to 95.5%) (Engel, 1997; Granata, 1999). Thus, the endoscopic approach is a reasonable alternative to ureteroneocystotomy; however, the long-term outcomes are not defined.

Continence and Prevention of Upper Urinary Tract Deterioration

The primary goals of management for children with myelomeningocele are the attainment of social continence and preservation of normal renal function. These goals can be achieved for most children with a combination of medical and surgical therapies.

Urinary continence is becoming an increasingly important issue that demands attention at an early age. It has been shown that children who are continent have higher ratings in self-confidence and social acceptance than boys and girls who are wet; thus this issue becomes paramount as the children grow up and attend school (Moore et al, 2004). Initial attempts at achieving continence include CIC and drug therapy designed to maintain low intravesical pressures and a reasonable level of urethral resistance (Figs. 128-10 and 128-11). Although these measures can be initiated on a trial-and-error basis, it is more efficient to use exact treatment protocols based on specific urodynamic findings. As a result, urodynamic testing is performed if initial attempts with CIC and oxybutynin fail to achieve continence. Without urodynamic studies it is hard to know whether (1) a single drug is effective, (2) the dose should be increased, (3) a second drug should be added to the regimen, or (4) alternative methods of treatment (i.e., augmentation cystoplasty) should be contemplated.

At this point, if poor detrusor compliance and/or overactivity have not been dealt with effectively the dose of the anticholinergic drug may be increased. If this is not successful, another anticholinergic agent may be combined with or given instead of oxybutynin (see Table 128–1). A recent study in adults with neurogenic bladder has shown the addition of a second anticholinergic agent to an existing double-dose anticholinergic agent resulted in improved urodynamic parameters and continence in 85% of patients who had failed single-agent therapy with minimal adverse effects (Amend, 2008). Glycopyrrolate is the most potent oral anticholinergic drug available today, but it may have the typical belladonna-like side effects common to all these drugs. Tolterodine, a newly approved anticholinergic drug, is equally effective as oxybutynin in reducing detrusor overactivity and improving compliance, but with fewer side effects, especially constipation (Goessl et al, 2000). Hyoscyamine produces fewer side effects still, but its potency is even less. Intravesical instillation of oxybutynin has been proven to be successful in lowering detrusor pressure and has fewer side effects compared with oral administration; serum concentrations may reach similar levels regardless of the route of intake (Greenfield and Fera, 1991; Massad et al, 1992). Inconvenience of administration, however, seems to preclude its long-term use (Kasabian et al, 1994). Trospium chloride, a recently approved quaternary ammonium compound with antimuscarinic activity that has a high binding affinity for muscarinic receptors M1, M2, and M3 but not nicotinic or cholinergic receptors holds promise because it has a more direct effect on detrusor function with fewer systemic side effects than anticholinergic agents (Rovner, 2004; Doroshyenko et al, 2005; Kim et al, 2005). Solifenacin, darifenacin, and propiverine are muscarinic receptor antagonists with high affinity for the M3 receptor. Propiverine also has calcium channel–blocking effects. These three novel agents may reduce adverse events; however, their safety and effectiveness has not yet been established in children. If conservative management with medications and CIC fail to achieve continence or prevent upper urinary tract deterioration, more aggressive intervention is warranted. In up to 80% of children, nocturnal bladder emptying has been shown to improve hydronephrosis, bladder compliance and capacity, urinary tract infections, and continence (Koff, 2005).

If urodynamic testing reveals that urethral resistance is inadequate to maintain continence because either the sphincter fails to react to increases in abdominal pressure or its resistance drops with bladder filling, α-sympathomimetic agents are added to the regimen (see Table 128–1); phenylpropanolamine is the most effective drug in this regard.

Some children will ultimately require surgical intervention. A persistent poorly compliant or overactive detrusor may be treated either with enterocystoplasty (Mitchell and Piser, 1987; Sidi et al, 1987; Hernandez et al, 1994), autoaugmentation (Cartwright and Snow, 1989a, 1989b), or a combination thereof (Duel et al, 1998). Sigmoid, cecum, and small intestine, in that order, have been used to enlarge the bladder. The ileocecal segment is avoided in children with myelodysplasia because removing it might aggravate the bowel dysfunction in these children. Detubularization of the bowel is needed to minimize the intrinsic contractions of the intestinal segment and prevent it from causing intractable incontinence once it has been added to the bladder (Goldwasser et al, 1987; Hinman, 1988). Concerns have surfaced about gastric segments because they can cause hyponatremic hypochloremic metabolic alkalosis (Gosalbez et al, 1993) or the hematuria dysuria syndrome (Nguyen et al, 1996). Except for children with progressive or end-stage renal failure, gastrocystoplasty has not been recommended as a routine form of augmentation (Leonard et al, 2000; Plaire et al, 2000).

With the long view of hindsight it is becoming evident that augmentation cystoplasty with any segment of the gastrointestinal tract can lead to long-term consequences in acid-base balance, vitamin B12 deficiency, fat absorption, renal function, bone metabolism, growth retardation, recurrent urinary tract infection, stone formation, and even cancer risk (Gilbert and Hensle, 2005). Consequently, there is considerable interest in developing new techniques for replacing the bladder without the need for bowel substitution (i.e., tissue-engineered autologous augments; see also Chapter 19).

The well-documented development of malignancy in patients with intestinal and gastric bladder augmentation mandates careful surveillance of these patients. Most studies note a 10-year minimum lag time between the augmentation and presentation of disease. Thus, 10 years after augmentation an annual surveillance cystoscopy with site-directed biopsies at the anastomotic suture line is recommended (Soergel et al, 2004; Castellan et al, 2007; Vemulakonda et al, 2008). Symptoms and signs such as new-onset hydronephrosis, hematuria, or bladder wall thickening warrant prompt evaluation (Castellan et al, 2007; Vemulakonda et al, 2008).

If bladder neck or urethral resistance is insufficient to allow adequate storage capacity, several operations are available to improve this continence mechanism. Bladder neck reconstruction can be undertaken in a variety of ways, including the Young-Dees or Leadbetter procedures (Young, 1919; Dees, 1949; Leadbetter, 1964) or the Kropp approach (Kropp and Angwafo, 1986), modified by Salle to make catheterization easier (Salle et al, 1994). A fascial sling procedure suspending the bladder neck and buttressing it against the undersurface of the pubis has been advocated enthusiastically by several clinicians (McGuire et al, 1986; Raz et al, 1988; Bauer et al, 1989). Artificially derived material, small intestine submucosa (SIS) (Colvert et al, 2002), and a rectus muscle “fascial” wrap around the bladder neck (Walker et al, 2000) have been as effective as rectus fascia in increasing bladder neck resistance and their effectiveness does not seem to dissipate over time (Elder, 1990; Castellan et al, 2005). Even though it is applicable to males it has not been as effective as in females (Nguyen et al, 2001; Castellan et al, 2005). Each of these operations, however, necessitates the use of CIC to empty the bladder postoperatively. It is most effective when combined with augmentation cystoplasty to ensure an adequate reservoir with good compliance (Castellan et al, 2005). The use of a bladder neck sling in conjunction with continent cutaneous catheterizable channel has been proposed to avoid bladder augmentation in some patients with neurogenic bladder. These children have a similar improvement in their continence level but may have a shorter interval between catheterization and require more anticholinergic agents than children with slings and augmentation (Snodgrass et al, 2009). However, this approach is controversial because of the potential risk of bladder deterioration related to increasing bladder pressures and lack of sufficient long-term follow-up. The artificial sphincter (Barrett and Furlow, 1982; Light and Scott, 1983; Light et al, 1983) also increases bladder outlet resistance, and its mechanism of action allows emptying at low urethral pressure. Any patient who can empty his or her bladder before the device is implanted should be able to do so afterward without the need for CIC. In fact, this is the only bladder neck procedure that allows for spontaneous voiding yet is compatible with CIC when needed (Herndon et al, 2003). However, children who have had bladder augmentation or an artificial sphincter placed before puberty are much more likely to require CIC to empty the bladder postpubertally (Catti, 2008). Poor detrusor compliance can develop postoperatively if the preoperative cystometrogram is not carefully scrutinized for signs of increased filling pressure (Woodside and McGuire, 1982; Bauer et al, 1986), and this may lead to progressive renal failure if not treated in a timely fashion with medication or augmentation cystoplasty (Bauer et al, 1993). Long-term results with the artificial sphincter have shown that it is a viable option in children with neurogenic bladder dysfunction (Bosco et al, 1991; Levesque et al, 1996; Kryger et al, 1999; Kryger et al, 2001; Herndon et al, 2003); however, device removal may be required in 9% to 20% (Lopez Pereira et al, 2006; Bauer, 2008; Catti, 2008).

An alternative, minimally invasive option to increase bladder outlet resistance is the endoscopic injection of bulking agents in the bladder neck (Ben-Chiam et al, 1995). Various bulking agents have been used. Early reports are usually promising; however, long-term results are less favorable (Perez et al, 1996; Silveri et al, 1998; Guys et al, 2001). Long-term data on newly developed injectable agents are not available (Caione and Capozza, 2002; Misseri et al, 2005).

Urinary diversion, once considered a panacea for children with myelodysplasia, has turned out to be a Pandora’s box of new clinical problems (Schwarz and Jeffs, 1975; Shapiro et al, 1975). Pyelonephritis and renal scarring, calculi, ureterointestinal obstruction, strictures of the conduit, and stomal stenosis are often encountered in children who are monitored on a long-term basis. Although antirefluxing colon conduits seem to have fewer complications, they are still not ideal. In the past 15 years very successful attempts have been made to reverse a urinary tract diversion in children who probably would not have undergone the procedure today (Hendren, 1973, 1990). Few children undergo urinary diversion now; if they do, it is in association with a continent catheterizable stoma.

Continent urinary diversion with complete closure of the bladder neck (or compression via a fascial sling) has been used to provide a better quality of life for those with intractable urethral incompetence despite bladder outlet surgery or to make it easier to catheterize those individuals who cannot easily catheterize themselves via their native urethra (MacNeily et al, 2005).

Several operations have been devised, but the ones that achieved the most publicity initially were the Kock pouch in adults (Kock, 1971; Skinner et al, 1987) and the Indiana reservoir in children (Rowland et al, 1987). Mitrofanoff (1980) created a continence mechanism by tunneling one end of the vermiform appendix into the bladder, as if reimplanting the ureter to prevent reflux, with the other end being brought out through the skin as a continent catheterizable stoma. This principle has been extended to the ureter. After the ureter is transected at the pelvic brim, a proximal transureteroureterostomy is performed and the cut end of the distal segment is brought to the skin as a stoma (Duckett and Snyder, 1986). Continence is achieved by the intramural detrusor tunnel of the ureter. Other narrow structures (e.g., fallopian tube, a rolled strip of stomach, a tapered or reconfigured ileal segment) have been implanted either into the native bladder or along the tinea of a detubularized portion of sigmoid or cecum when the latter act as a urinary reservoir (Woodhouse et al, 1989; Reidmiller et al, 1990; Bihrie et al, 1991; Montie et al, 1997). The success rate for achieving continence has been excellent, approaching 85%, primarily owing to the flap valve effect of the intramural tunnel (Hinman, 1990; Watson et al, 1995; Kaefer et al, 1997; Gerharz et al, 1998). For this reason, it is now the preferred method for continent urinary diversion (Harris et al, 2000).

An alternative option for achieving continence and improving urodynamic parameters is the intravesical injection of botulinum-A toxin, which is a neurotoxin protein produced by Clostridium botulinum that acts by inhibiting acetylcholine release, resulting in muscle paralysis. The commonly injected dose ranges from 5 to 12 IU/kg, with a maximum total dose of up to 360 IU. Sixty-five to 87 percent of children who have failed conservative medical management and CIC have achieved dryness with a botulinum-A injection. Improvements in urodynamic parameters include decreased maximum detrusor pressure (33% to 57%); increased maximum cystometric capacity (34% to 165%); and improved compliance (121% to 183%) (Schulte-Baukloh et al, 2002; Riccabona et al, 2004; Altaweel et al, 2006; Kajbafzadeh et al, 2006). The duration of response ranges from 6 to 10.5 months. It appears that repeated injections continue to be effective with the interval between repeated injections increasing with each series of injections (Schulte-Baukloh et al, 2005; Altaweel et al, 2006). Complete lack of a response to botulinum-A injection has been linked to the presence of botulinum-A antibodies (Schulte-Baukloh et al, 2008).

The artificial somatic-autonomic reflex pathway is a promising new therapeutic approach to restore bladder function in children with spina bifida. The procedure involves a limited laminectomy and a lumbar ventral root to S3 ventral root microanastomosis. The L5 dorsal root is left intact as the afferent branch of the somatic-autonomic reflex pathway after axonal regeneration (Xiao et al, 2005). In a series of 20 children with spina bifida, 17 developed satisfactory bladder control and continence within 12 months of the procedure. Those children with DSD and overactivity demonstrated nearly normal storage and synergic voiding on follow-up urodynamic studies (Xiao, 2005). A recent study at an independent center confirmed early favorable results with improved continence and spontaneous voiding in 30% of the spina bifida patients (median age 8 years) who underwent intradural lumbar to sacral motor root microanastomosis. Postoperative complications included prolonged wound drainage, ipsilateral footdrop, and temporary lower extremity muscle weakness (Peters et al, 2010). Thus this novel approach appears to have promising results when preformed by experts. The long-term results and general application of the procedure are yet to be determined.

Sexuality

Sexuality in this population is becoming an increasingly important issue as more individuals reach adulthood and want to marry or to have intimate relationships (Cromer et al, 1990). Investigators are looking into the concerns, fears, self-imagery, and desires of teenagers and young adults and at the ability of males to procreate and females to bear children (Bomalaski et al, 1995). However, few studies are available that look critically at sexual function in these patients. Mental disability, poor manual dexterity, lack of education regarding normal and abnormal sexual function, invasion of personal privacy, and overprotective parents often prevent independent behavior and, as a result, lead to poor understanding of sexual issues (Joyner et al, 1998; Woodhouse, 2005).

In several studies, researchers interviewed groups of teenagers and reported that 28% to 40% of them had had one or more sexual encounters and almost all of them had a desire to marry and ultimately to bear children (Cromer et al, 1990; Palmer et al, 1999a). In one study, 72% of male subjects claimed they were able to have an erection, and two thirds of these were able to ejaculate (Decter et al, 1997). Medical therapy has been shown to be effective in this population. Sildenafil improved erectile function in 80% of men with meningomyelocele in a randomized, double-blind, placebo-controlled trial (Palmer et al, 2000). Other studies revealed that 70% to 80% of myelodysplastic women were able to become pregnant and to have an uneventful pregnancy and delivery, although urinary incontinence in the latter stages of gestation was common in many, as was delivery by cesarean section (Laurence and Beresford, 1975; Cass et al, 1986; Bomalaski et al, 1995; Arata et al, 2000). In the same studies, 17% to 39% of male subjects claimed that they were able to father children and another 25% had a good prognosis for fathering them (Laurence and Beresford, 1975; Bomalaski et al, 1995; Decter et al, 1997). It is more likely that men will have problems with erectile and ejaculatory function because the sacral spinal cord is frequently involved, whereas reproductive function in women, which is under hormonal control, is not affected. Men with neurologic lesions at S1 or lower are likely to have normal or adequate reproductive sexual function, but only 50% of those with lesions above that level have adequate function (Woodhouse, 1994, 2005). Poor semen quality (Reilly and Oates, 1992) and Sertoli cell–only histology on testis biopsy (Glass and Soni, 1999) have been reported as reasons (in addition to erectile dysfunction) for infertility in males with spina bifida.

The degree of sexuality is inversely proportional to the level of neurologic dysfunction (Joyner et al, 1998; Palmer et al, 1999b). Until recently, however, this subject has been taboo (Decter et al, 1997). Sexual identity, education, and social mores have been taken out of the realm of secrecy and are now openly discussed. However, parents of children with spina bifida are more overprotective than parents of normal children and are less willing to grant autonomy to them for adequate peer and sexual development (Holmbeck et al, 2002); this tends to lead to less self-assurance regarding social interaction with the opposite sex and diminished sexual identity. Boys reach puberty at an age similar to the age for normal males, whereas breast development and menarche tend to start as much as 2 years earlier than usual in myelodysplastic compared with normal girls. The cause of this early hormonal surge is uncertain, but it may be related to changes in pituitary function in girls secondary to hydrocephalus (Hayden, 1985).

Bowel Function

There is no unanimity regarding the ideal bowel management program for myelodysplastic children. The external anal sphincter is innervated by the same (or similar) nerves that modulate the external urethral sphincter, whereas the internal anal sphincter is under the influence of more proximal nerves from the sympathetic nervous system. In addition, the internal anal muscle reflexively relaxes in response to anal distention. Consequently, bowel incontinence is frequently unpredictable and is not associated with the attainment of urinary continence; it is often related to the consistency of fecal material and how rapidly the anal area refills after an evacuation, the degree of intactness of sacral cord sensation and motor function, and reflex reactivity of the external anal sphincter muscle (Younoszai, 1992).

A majority of pediatricians managing these children believe that a regular and efficient bowel emptying regimen is paramount and mandatory. Most programs begin at about 1 year of age, but the best method of attaining these objectives is still controversial. Usually the children are placed on diets that are intended to create formed but not severely constipated stool. Roughage in the form of fruits and bran and stool softeners (in older children) are given to achieve this goal. Suppositories that help evacuate the rectum are used on a regular basis to help train the lower bowel to fill and empty. Some physicians believe that enemas are more effective in evacuating a greater portion of the lower bowel, but one problem with them is the difficulty of retaining the solution when the anal sphincter muscle is lax. Biofeedback training programs to strengthen the external anal sphincter are no more effective than a good bowel management program in attaining fecal continence (Loening-Baucke et al, 1988). Whereas electrostimulation of the bowel has had a variable effect in fecal continence, ranging from 0% to 36% (Marshall and Boston, 1997; Palmer et al, 1997), intravesical bladder stimulation has had a more pronounced effect on bowel continence (Han et al, 2004). When a carefully constructed bowel regimen is adhered to, most children with myelomeningocele can achieve some degree of fecal continence (Myers, 1984), but the uncertainty of accidents always makes this a tenuous situation. Often the urinary incontinence is effectively managed with CIC, drugs, and/or surgery but episodes of fecal soiling remain a problem, particularly in socially minded adolescents (Hayden, 1985; Krogh et al, 2003). When diet, medications, and manual evacuation fail to achieve predictable bowel emptying without soiling, a continent cutaneous pathway from the lower abdominal wall to the cecum may be created using the vermiform appendix; this is called the ACE procedure, for Antegrade Continence Enema (Griffiths and Malone, 1995). When the appendix is unavailable, a small segment of the bowel may be reconfigured to act as a conduit. Alternatively, a button cecostomy provides effective access for antegrade continence enemas (Duel, 1999). Enemas consisting of either Golytely, saline, or tap water, sometimes in combination with bisacodyl, are instilled daily or every other day to evacuate the colon. Cleansing the colon in this manner has resulted in complete continence in 89% of children in whom it has been tried (Squire et al, 1993; Gerharz et al 1997; Yerkes et al, 2002). Older children readily become independent in managing their bowel function, leading to improved self-esteem and sociability (Bau et al, 2001; Aksnes et al, 2002).

Lipomeningocele and Other Spinal Dysraphisms

Diagnosis

There is a group of congenital defects that affect the formation of the spinal column but do not result in an open vertebral canal (James and Lassman, 1972) (Table 128–4). They occur once in 4000 live births, but with the ease of MRI screening of children with suspected lesions the incidence of these defects is increasing (Bruce and Schut, 1979). In a recent study the incidence of lipomeningocele in families was calculated to be 0.043% (Sebold et al, 2005). These lesions can be very subtle and have no obvious outward signs, but in more than 90% of children there is a cutaneous abnormality overlying the lower spine (Anderson, 1975; Pierre-Kahn et al, 1997). This varies from a small dimple or skin tag to a tuft of hair, a dermal vascular malformation, a very noticeable subcutaneous lipoma, or an asymmetrically curving gluteal cleft (Fig. 128–12). In addition, on careful inspection of the legs, one may note a high arched foot or feet; hammer toes or claw toes; a discrepancy in muscle size, shortness, and decreased strength in one leg compared with the other, typically at the ankle; and/or a gait abnormality, especially in older children (Dubrowitz et al, 1965; Weissert et al, 1989; Jindal and Mahaptra, 2000). Absent perineal sensation, back pain, and secondary incontinence after a period of dryness are common symptoms in older children and young adults (Linder et al, 1982; Yip et al, 1985; Weissert et al, 1989). Lower urinary tract function is abnormal in 40% to 90% of affected older individuals, with the incidence of an abnormality increasing proportionately with age (Mandell et al, 1980; Koyangi et al, 1997; Pierre-Kahn et al, 1997; Sarica et al, 2003). The child may experience difficulty with toilet training, urinary incontinence after an initial period of dryness once toilet trained (especially during the pubertal growth spurt), recurrent urinary infection, and/or fecal soiling. Occasionally, some patients without an obvious back lesion escape detection until they develop urinary (66%) or lower extremity (19%) symptoms or back pain (14%) after puberty caused by delayed traction on the spinal cord (Satar et al, 1995).

Table 128–4 Types of Occult Spinal Dysraphisms

Findings

When these children are evaluated in the neonatal period or early infancy, a majority have a perfectly normal neurologic examination (Atala et al, 1992). Urodynamic testing, however, reveals abnormal lower urinary tract function in about one third of infants younger than 18 months of age (Keating et al, 1988) (Fig. 128–13). Such studies may provide the only evidence of a neurologic injury involving the lower spinal cord (Keating et al, 1988; Foster et al, 1990; Atala et al, 1992, Satar et al, 1997; Nogueira et al, 2004). When present, the most likely abnormality is an upper motor neuron lesion characterized by an overactive detrusor and/or hyperactive sacral spinal cord reflexes (Fone et al, 1997; Pierre-Kahn et al, 1997); mild forms of DSD are rarely noted. Lower motor neuron signs with denervation potentials in the sphincter or an acontractile detrusor occur in only 10% of young children.

In contrast, practically all individuals older than 3 years of age who have not been operated on or in whom an occult dysraphism has been belatedly diagnosed have either an upper or lower motor neuron lesion or a combination thereof on urodynamic testing (92%) (see Fig. 128–13) or neurologic signs of lower extremity dysfunction (Yip et al, 1985; Kondo et al, 1986; Keating et al, 1988; Atala et al, 1992; Satar et al, 1997; Nogueira et al, 2004). When such children were observed expectantly from infancy after the diagnosis was made, 58% experienced deterioration of their disorder within 2 years (Andar et al, 1997; Cornette et al, 1998). There does not seem to be a preponderance of one type of lesion over another (i.e., upper vs. lower motor neuron); and often the child shows signs of both (Hellstrom et al, 1986; Kondo et al, 1986). In one study of children older than 3 years of age, 43% had denervation in the sphincter and 52% detrusor areflexia, with a total of 81% having an abnormality (Satar et al, 1995).

Pathogenesis

Various occult spinal dysraphic lesions produce different neurourologic findings. When they do cause an abnormality, lipomas of the cauda equina invariably cause an upper motor neuron lesion (70%), alone or in combination with a lower motor neuron deficit (30%) (Satar et al, 1997). The split cord syndrome results in an isolated upper or lower motor neuron lesion in 25% each or a combined lesion in 50% (Proctor et al, 2000).

The reason for this difference in neurologic findings may be related to (1) compression on the cauda equina or sacral nerve roots by an expanding lipoma or lipomeningocele (Yamada et al, 1983), (2) tension on the spinal cord from tethering secondary to differential growth rates in the bony vertebrae and neural elements while the lower end of the cord is held in place by the lipmoa or by a thickened filum terminale (Dubrowitz et al, 1965), or (3) fixation of the split lumbosacral cord by an intravertebral bony spicule or fibrous band (Pang, 1992; Pang et al, 1992; Andar et al, 1997). The overt stretching that invariably occurs when there is a forcible flexion and/or extension of the spinal cord with normal movement leads to changes in oxidation/reduction of cytochrome oxidase, most notably in the lumbosacral spinal neurons when there is no intraspinal pathologic process (Yamada et al, 2004; Henderson et al, 2005). Under normal circumstances the conus medullaris ends just below the L2 vertebra at birth and recedes upward to T12 by adulthood (Barson, 1970). When the cord does not “rise” or is fixed in place owing to one of these lesions, ischemic injury may ensue (Yamada et al, 1981, 2004). Correcting the lesion in infancy has resulted not only in stabilization but also in improvement in the neurologic picture in many instances (Koyangi et al, 1997, Cornette et al, 1998; Proctor et al, 2000) (Fig. 128–14). Sixty percent of infants with abnormal urodynamic findings preoperatively revert to normal postoperatively, with improvement noted in 30%; 10% become worse with time. In older children there is a less dramatic change after surgery, with only 27% becoming normal, 27% improving, 27% stabilizing, but 19% actually becoming worse with time (see Fig. 128–14) (Keating et al, 1988; Satar et al, 1997). Older children with an overactive detrusor tend to improve, whereas those with acontractile bladders do not (Hellstrom et al, 1986; Kondo et al, 1986; Flanigan et al, 1989). Finally, 5% to 27% of children operated on in early childhood develop secondary tethering when observed for several years, suggesting that early surgery has both beneficial and sustaining effects in patients with this condition (Pierre-Kahn et al, 1997; Satar et al, 1997; Proctor et al, 2000).

As a result of these findings, it is apparent that urodynamic testing may be the only way to document that an occult spinal dysraphism is actually affecting lower spinal cord function (Keating et al, 1988; Khoury et al, 1990; Sarica et al, 2003). The serial use of electromyography of the external urethral sphincter using a needle electrode to monitor individual motor unit action potentials provides a precise mechanism for measuring changes in innervation that may occur over time. Some investigators have shown that posterior tibial somatosensory evoked potentials are an even more sensitive indicator of tethering and should be an integral part of the urodynamic evaluation (Roy et al, 1986). The implication of these findings lies in the fact that early detection and early intervention can either reverse or at least stabilize the progression of the lesion, which does not happen in older children (Yamada et al, 1983; Tami et al, 1987; Kaplan et al, 1988) and offers a degree of protection from subsequent tethering (Pierre-Kahn et al, 1997; Satar et al, 1997; Proctor et al, 2000), which seems to be a frequent occurrence when the lesion is not dealt with expeditiously in infancy (Chapman, 1982; Seeds and Jones, 1986).

Recommendations

In addition to MRI studies (Tracey and Hanigan, 1990), urodynamic testing including EMG of the external urethral sphincter should be performed in every child who has a questionable cutaneous or bony abnormality of the lower spine, especially if there is a radiologic abnormality of the spinal cord (Packer et al, 1986; Campobasso et al, 1988; Hall et al, 1988; Meyrat et al, 2003). This test provides the most accurate measure of sacral spinal cord function at diagnosis and provides a basis for comparison with subsequent studies when the children are either operated on or carefully observed. In children younger than 3 months of age the vertebral bones have not ossified; thus a window of opportunity exists for ultrasonography to be a useful screening tool in visualizing the spinal canal (Fig. 128–15) (Raghavendra et al, 1983; Scheible et al, 1983). At this age there is good correlation between the ultrasound imaging and MRI findings; however, if a spinal cord abnormality is identified the latter provides for a better definition of the spinal cord lesion. Consequently, ultrasonography should not be used as the definitive imaging modality (Hughes et al, 2003). Older children with an occult spinal cord lesion may have urologic symptoms in 20% of cases (Hsieh et al, 2006), and 50% to 60% may have abnormal urodynamic findings preoperatively (Geurra et al, 2006). Resolution of the abnormal urodynamic parameters is noted in 50% to 60% of cases after detethering (Hseih et al, 2006; Geurra et al, 2006). Therefore, urodynamic study is recommended for all children with an occult spinal dysraphism before and after spinal cord detethering procedures.

In the past, most of these conditions were treated by excising the superficial skin lesion, without dissecting further into the spinal canal to remove or repair the entire abnormality. Currently, most neurosurgeons advocate laminectomy and removal of the intraspinal process as completely as possible without injuring the nerve roots or cord to release the tether and prevent further injury with subsequent growth (Linder et al, 1982; Kondo et al, 1986; Kaplan et al, 1988; Foster et al, 1990; Atala et al, 1992; Pierre-Kahn et al, 1997; Proctor et al, 2000; Jindal and Mahapatra, 2000; Nogueira et al, 2004).

Sacral Agenesis

Sacral agenesis has been defined as the absence of part or all of two or more lower vertebral bodies. The cause of this condition is still uncertain, but teratogenic factors may play a role, because insulin-dependent diabetic mothers have a 1% chance of giving birth to a child with this disorder. Conversely, 16% or more of children with sacral agenesis have a mother who is insulin dependent with diabetes mellitus (Passarge and Lenz, 1966; Guzman et al, 1983; Wilmshurst et al, 1999). Often the mothers have only gestational insulin-dependent diabetes. The disease has been reproduced in chicks by exposing embryos to insulin (Landauer, 1945; White and Klauber, 1976). Maternal insulin-antibody complexes have been noted to cross the placenta, and their concentration in the fetal circulation is directly correlated with macrosomia (Menon et al, 1990). It is possible that a similar cause-and-effect phenomenon occurs in sacral agenesis. There is evidence that a deletion of the seventh chromosome (7q36) leading to the absence of a transcription factor may be responsible for this anomaly (Papapetrou et al, 1999). In addition, maternal drug exposure (i.e., minoxidil) has been reported to cause sacral agenesis (Rojansky et al, 2002).

In familial cases of sacral agenesis associated with the Currarino syndrome (presacral mass, sacral agenesis, and anorectal malformation), deletions in chromosome 7 (7q) resulting in HLXB9 genetic mutations have been found (Ross et al, 1998). A mutation in HLXB9, a homeodomain gene of a 403 amino acid protein that appears to be responsible for neural plate infolding, has been identified in 20 of 21 patients with familial cases and in 2 of 7 sporadic cases of Currarino syndrome (Hagan et al, 2000; Kochling et al, 2001). Heterozygote carriers within these families have also been identified (Lynch et al, 2000). Thus, sacral agenesis may represent one point on a spectrum of abnormalities that encompass sacral meningoceles and anorectal malformations (Bernbeck et al, 2004).

Diagnosis

The presentation is bimodal, with more than three fourths of the disorders being detected in early infancy and the remainder discovered between 4 and 5 years of age (Wilmshurst et al, 1999). With the increased use of prenatal ultrasonography, it is being diagnosed with increased frequency before birth. Sacral vertebral bony ossification begins at 15 weeks, so it is possible to detect the lesion after 18 weeks of gestation on an ultrasound examination and then to confirm it by fetal MRI (De Biasio et al, 2003). When not detected prenatally or at birth, the diagnosis is often delayed until failed attempts at toilet training bring the child to the attention of a physician. Sensation, including that in the perianal dermatomes, is usually intact, and lower extremity function is normal (Koff and DeRidder, 1977; Jakobson et al, 1985; Capitanucci et al, 1997). Because these children have normal sensation and little or no orthopedic deformity in the lower extremities (although high arched feet or claw toes or hammer toes may be present), the underlying lesion is often overlooked. In fact, 20% escape detection until the age of 3 or 4 years (Guzman et al, 1983). The only clue, besides a high index of suspicion, is flattened buttocks and a low, short gluteal cleft (Bauer, 1990) (Fig. 128–16). Palpation of the coccyx is helpful in detecting the absent vertebrae (White and Klauber, 1976). The diagnosis is most easily confirmed with a lateral film of the lower spine, because this area is often obscured by the overlying gas pattern on an anteroposterior projection (White and Klauber, 1976; Guzman et al, 1983) (Fig. 128–17). MRI has been used to visualize the spinal cord in these cases; its imaging reveals a sharp cutoff of the conus at T12 as a consistent finding (Pang, 1993; Diel et al, 2001) (Fig. 128–18).

Findings

On urodynamic evaluation an almost equal number of individuals manifest either an upper or a lower motor neuron lesion (35% vs. 40%, respectively); 25% have no sign of denervation (Guzman et al, 1983; Boemers et al, 1994). The number of affected vertebrae does not seem to correlate with the type of motor neuron lesion present (Boemers et al, 1994) (Fig. 128–19). The injury appears to be stable and rarely shows signs of progressive denervation as the child grows. Sacral sensation is relatively spared, even in the presence of extensive sacral motor deficits (Boemers et al, 1994; Schlussel et al, 1994). Urinary tract infection may be detected in 75% of children over time, with vesicoureteral reflux diagnosed in 37%. Reflux is most likely to occur in those with an upper (75%) (irrespective of whether they have synergy or dyssynergy) versus a lower (40%) motor neuron lesion (Schlussel et al, 1994; Wilmshurst et al, 1999).

Recommendations

Because most children who are diagnosed with this condition have a neurologic deficit, urodynamic testing is mandatory at the time of diagnosis. Renal ultrasonography and nuclear or conventional cystography should be included as part of the evaluation process, especially if the child has a history of urinary tract infection or findings of an upper motor neuron lesion on urodynamic testing. Additional imaging studies may be required based on the child’s history and findings from baseline studies.

Management depends on the specific type of neurourologic dysfunction seen on urodynamic testing. Anticholinergic agents should be given to children with upper motor neuron findings of detrusor overactivity, whereas CIC and α-sympathomimetic medications may have to be given to individuals with lower motor neuron deficits who cannot empty their bladders or stay dry between catheterizations. When anticholinergic medication is ineffective in controlling the overactive detrusor, augmentation cystoplasty may be required to attain an adequate organ for urinary storage. Failure of α-sympathomimetic agents may require either endoscopic injection of bulking agents or even artificial urinary sphincter implantation to increase bladder outlet resistance. The bowels manifest a similar picture of dysfunction and need as much characterization and treatment as the lower urinary tract. Anorectal manometry has identified abnormalities in the internal anal sphincter and in voluntary anal sphincter squeeze pressure, leading to weakness of the muscle and concomitant fecal incontinence (Morera and Nurko, 2003). It is important to identify these individuals as early as possible so that they can become continent and out of diapers at an appropriate age, thus avoiding the social stigma of fecal or urinary incontinence.

Imperforate Anus

Imperforate anus is a condition that can occur alone or as part of a constellation of anomalies that have been called the VATER or VACTERL syndrome (Barry and Auldist, 1974). This mnemonic denotes all the regions or structures that can possibly be affected (vertebral, anal, cardiac, tracheo-esophageal fistula, renal, limb). The incidence of anorectal malformations varies between 1 in 4000 to 1 in 5000 live births (Templeton and O’Neill, 1986). There is a male predominance of 1.5:1. The majority of female patients have low lesions, whereas males tend to have high ones (Santulli et al, 1971). Several classification systems have been devised, but the most commonly used one is the Wingspread Workshop on Anorectal Malformations (Table 128–5) (Shaul and Harrison, 1997). This format attempts to divide the lesions into high, intermediate, or low, depending on whether the rectum ends above, at, or below the levator ani muscle, respectively. The relative incidence for the various levels of the defect is 36% high, 14% intermediate, 47% low, and 1% a cloacal lesion. Imperforate anus may be part of a spectrum of hindgut abnormalities that include sacral agenesis and even a presacral mass or meningocele recently labeled as Currarino syndrome (Currarino et al, 1981; Hagan et al, 2000), which has genetic implications (Ross et al, 1998).

Table 128–5 Wingspread Classification of Anorectal Malformations

  FEMALE MALE
High Anorectal agenesis Anorectal agenesis
  With rectovaginal fistula With rectourethral (prostatic) fistula
  Without fistula Without fistula
  Rectal atresia Rectal atresia
Intermediate Rectovestibular fistula Rectovestibular urethral fistula
  Rectovaginal fistula Anal agenesis without fistula
  Anal agenesis without fistula  
Low Anovestibular fistula Anocutaneous fistula
  Anocutaneous fistula Anal stenosis
  Anal stenosis Rare malformation
  Cloacal malformation  
  Rare malformation  

Associated Findings

A fistulous communication with the lower urinary tract is a common occurrence, related in part to the sex of the child and the extent of the lesion: 87% of male and 79% of female infants with a high or intermediate lesion have a connection, whereas 7% of male and 10% of female children with a low lesion have such a communication (Templeton and O’Neill, 1986; Holschneider et al, 1994). Urinary tract abnormalities have been noted in 26% to 52% of affected children, with renal agenesis (primarily left-sided) and vesicoureteral reflux as the most common associated findings (Parrott, 1985). Again, the highest incidence of an abnormality is in those children with a high (70%) versus a low (infralevator) (35%) lesion (Shaul and Harrison, 1997; Emir and Soylet, 1998), with boys more prone than girls to having an anomaly (50% vs. 29%) (Metts et al, 1997). Spinal bony abnormalities range in incidence from 30% to 44%, but patients with a high lesion are more likely to be affected (48% to 54%) than those with a low lesion (15% to 27%) (Carson et al, 1984; Tsakayannis and Shamberger, 1995; Long et al, 1996). Spinal cord abnormalities including a tethered cord, thickened or fatty filum terminale, and a lipoma have been noted in 18% to 50% of patients, with the incidence varying proportionately in relation to the height of the rectal lesion (Shaul and Harrison, 1997). Not all patients with a spinal cord abnormality have a bony defect, so intraspinal imaging is mandatory to ensure the presence of a normal spinal cord, especially in cases of high lesions (Rivosecchi et al, 1995). On occasion, an abnormal spinal cord can be found in patients even without one of these commonly associated other anomalies. Neurogenic bladder dysfunction is a frequent finding (Kakizaki et al, 1994), usually manifesting as incontinence, but its occurrence is rare when no spinal cord malformation exists (Hulthen de Medina et al, 2004) (Fig. 128–20). It often manifests when the child is older and the parents have difficulty with toilet training. It is not certain whether the dysfunction is caused by a spinal cord defect or by trauma to the nerves supplying the lower urinary tract or the pelvic floor musculature occasioned during surgery to repair the spinal cord or rectal defect (Parrott and Woodard, 1979). With the advent of the Peña posterior sagittal midline approach, the latter etiology is less likely (Peña, 1986; Boemers et al, 1994). Despite careful dissection techniques, 37% still have long-term problems with fecal incontinence (Peña and Hong, 2000).

Neonatal Assessment

Initial evaluation in the neonatal period should include a careful inspection of the perineum looking for a fistulous site from the bowel, an examination of the upper and lower extremities, and an assessment of the spine and spinal cord (Carson et al, 1984; Mosiello et al, 2003). A prone cross-table lateral image with the child held in that position for 3 minutes and a radiopaque marker placed on the perineum will help delineate the distance from the end of the rectum to the skin in order to classify the extent of the rectal defect. Gas, meconium, or a gram-negative infection in the urine strongly suggests a rectal/urinary tract fistula, which then necessitates a divided colostomy very early in the postnatal period. Once the child is stable clinically, radiologic investigation of the urinary tract is begun, first with renal ultrasonography and then with VCUG, to define the presence of an abnormality and discover any clues for possible neurogenic bladder dysfunction. Vertebral bony anomalies, especially sacral level lesions, often signify an underlying spinal cord abnormality (Boemers et al, 1996). Thus any bony abnormality warrants ultrasonography of the spine if the child is younger than 3 months of age because the vertebral bodies have not ossified and a spinal MRI to rule out any abnormal intraspinal process (see Fig. 128–20) (Barnes et al, 1986; Tunell et al, 1987; Emir and Soylet 1998; Karrer et al, 1988; Mosiello et al, 2003). Urodynamic studies including sphincter electromyography are reserved for those children with either a bony abnormality of the spine, a spinal cord defect, or the telltale signs of dysfunction on VCUG or renal ultrasonography (Taskinen et al, 2002; Mosiello et al, 2003). These studies should be conducted early in infancy before the child has had any definitive surgery for the imperforate anus and again after a pull-through operation has been performed on the rectum to determine, respectively, the true incidence of neurogenic bladder dysfunction and any changes that might have occurred as a result of the surgery. The presence of an abnormality on urodynamic testing in early infancy may warrant either intervention at that time to correct a spinal cord defect or watchful waiting to determine whether the lesion is progressive. Urodynamic studies are repeated subsequently or performed for the first time if secondary urinary or fecal incontinence ensues (Taskinen et al, 2002).

The most common finding on urodynamic testing is an upper motor neuron lesion with an overactive detrusor and/or DSD (Boemers et al, 1994; Taskinen et al, 2002), but a lower motor neuron lesion with an acontractile detrusor and a denervated sphincter may be seen as well (see Fig. 128–20) (Greenfield and Fera, 1991; Taskinen et al, 2002). EMG assessment of the perianal musculature at this time helps determine the exact location of the future anus. In addition, it can provide precise information about the innervation to the levator ani muscle and its competence to function as a sphincter. The posterior midline approach espoused by Peña (1986) minimizes the chances of injuring the pelvic nerves that innervate the pelvic floor muscles and therefore reduces the risk of an iatrogenic cause for neurogenic bladder dysfunction.

Central Nervous System Insults

Cerebral Palsy

Pathogenesis

Cerebral palsy is a nonprogressive injury of the brain occurring in the perinatal period that results in either a neuromuscular disability, a specific symptom complex, or cerebral dysfunction (Kuban and Leviton, 1994). Its incidence is approximately 1.5 per 1000 births, but the incidence is increasing as smaller and younger premature infants survive in intensive care units (Kuban and Leviton, 1994). The condition is usually caused by a perinatal infection (e.g., sepsis, meningoencephalitis) or by a period of anoxia (or hypoxia) that affects the CNS (Nelson and Ellenberg, 1986; Naeye et al, 1989). It most commonly appears in infants who were premature, weighed less than 2 kg at birth, had intraventricular hemorrhage, and received mechanical ventilation for a prolonged time in the postnatal period and in premature infants weighing more than 2 kg who experienced a neonatal seizure (Kim et al, 1999). Maternal urinary infection in the later stages of pregnancy increases the risk of having an affected child by four to five times (Polivka et al, 1997).

Diagnosis

Affected children have delayed gross motor development, abnormal fine motor performance, altered muscle tone, abnormal stress gait, and exaggerated deep tendon reflexes. These findings can vary substantially, from obvious to very subtle when no discernible lesion is present, unless a careful neurologic examination is performed. These abnormalities may not manifest in the postnatal period, but they do become evident over time, because myelination of axons and maturation of neurons in the basal ganglia are required before spasticity, dystonia, and athetosis become apparent (Kyllerman et al, 1982). The lesions are classified according to which extremities are involved (monoplegia, hemiplegia, diplegia, and quadriplegia) and what kind of neurologic dysfunction is present (spastic, hypotonic, dystonic, athetotic, or a combination thereof). Among the more overtly affected individuals, spastic diplegia is the most common of the five types of dysfunction that characterize this disease, accounting for almost two thirds of the cases (Kuban and Leviton, 1994).

Findings

Most children with cerebral palsy develop total urinary control. Incontinence is a feature in some, but the exact incidence has never been truly determined (McNeal et al, 1983; Decter et al, 1987). In a recent survey of questionnaires sent to over 600 families with an affected child aged 4 to 18 years, 23.5% had persistent urinary incontinence (Roijen et al, 2001). When urinary continence was achieved, its development was delayed when compared with normal children of similar age. With further analysis of the data, 80% of children with spastic diplegia, 54% with tetraplegia, and 38% with low intellectual capacity attained continence. The presence of incontinence is often related to the extent of the physical impairment, because the handicap prevents the child from getting to the bathroom on time, causing an episode of wetting (Murphy et al, 1995). A number of children have such a severe degree of mental retardation that they are not trainable. They either do not recognize the need to void or cannot relate this fact to caregivers early enough to be toileted successfully (Roijen et al, 2001). The majority, however, have sufficient intelligence to learn basic societal protocols with patient and persistent handling. When continence is achieved (usually at a later than expected age), diurnal continence is attained first with nocturnal continence occurring within the subsequent year (Roijen et al, 2001). Therefore, urodynamic evaluation is reserved for children who appear to be trainable and do not seem to be hampered too much by their physical impairment but who have not achieved continence by late childhood or early puberty.

In one review (Decter et al, 1987), urodynamic studies were performed in 57 children with cerebral palsy (Table 128–6). Forty-nine (86%) had the expected picture of a partial upper motor neuron type of dysfunction, with exaggerated sacral reflexes, an overactive detrusor and/or DSD (Fig. 128–21), even though they manifested voluntary control over voiding. Six (11%) of the 57 had evidence of both upper and lower motor neuron denervation with an acontractile detrusor or abnormal motor unit potentials on sphincter EMG assessment (Table 128–7). Most of the children who exhibited these latter findings were found to have an episode of cyanosis in the perinatal period when their records were analyzed on a retrospective basis (Table 128–8). Therefore, a lower motor neuron lesion may be seen in addition to the expected upper motor neuron dysfunction. Similar findings have been noted subsequently (Mayo, 1992; Reid and Borzyskowski, 1993).

Table 128–6 Lower Urinary Tract Function in Cerebral Palsy

TYPE NO. PATIENTS %
Upper motor neuron lesion 49 86
Mixed upper + lower motor neuron lesion 5 9.5
Incomplete lower motor neuron lesion 1 1.5
No urodynamic lesion 2 3

Adapted from Decter RM, Bauer SB, Khoshbin SJ, et al. Urodynamic assessment of children with cerebral palsy. J Urol 1987;138:1110.

Table 128–7 Urodynamic Findings in Cerebral Palsy*

TYPE OF LESION NO. PATIENTS
Upper Motor Neuron  
Uninhibited contractions 35
Detrusor sphincter dyssynergy 7
Hyperactive sacral reflexes 6
No voluntary control 3
Small-capacity bladder 2
Hypertonia 2
Lower Motor Neuron  
Excessive polyphasia 5
↑ Amplitude + ↑ duration potentials 4

* Some patients had more than one finding.

Adapted from Decter RM, Bauer SB, Khoshbin S, et al. Urodynamic assessment of children with cerebral palsy. J Urol 1987;138:1110.

Table 128–8 Perinatal Risk Factors in Cerebral Palsy

FACTOR UPPER MOTOR NEURON LESION
(NO. PATIENTS)		 LOWER MOTOR NEURON LESION
(NO. PATIENTS)
Prematurity 10 1
Respiratory distress/arrest/apnea 9 2
Neonatal seizures 5 —
Infection 5 —
Traumatic birth 5 —
Congenital hydrocephalus 3 —
Placenta previa/abruption 2 2
Hypoglycemia ± seizures 2 —
Intracranial hemorrhage 2 —
Cyanosis at birth 1 3
No specific factor noted 15 —

Adapted from Decter RM, Bauer SB, Khoshbin S, et al. Urodynamic assessment of children with cerebral palsy. J Urol 1987;138:1110.

In two more recent reviews of 65 children with cerebral palsy undergoing urodynamic studies (Bross et al, 2004; Karaman et al, 2005), abnormal bladder and urethral sphincter function was found in almost all. In the first study involving 29 (Bross et al, 2004), 23 had incontinence and/or urinary tract infection whereas 6 were asymptomatic; urodynamic studies demonstrated poor compliance in 21 of the 23 symptomatic and 2 of the 6 asymptomatic children, an overactive detrusor in all symptomatic and 5 of 6 asymptomatic children, and high leak point pressure in 16 of 23 and 4 of 6 symptomatic and asy-mptomatic children, respectively. VCUG revealed bladder trabeculation in 58% and reflux in 9% of symptomatic children, and trabeculation in 50% but no reflux in the asymptomatic children. In the other study (Karaman et al, 2005), 66% had dysfunctional voiding symptoms, including 47.2% with daytime incontinence and 44.4% with difficulty urinating. Neurogenic detrusor overactivity was present in 47.2%, and dyssynergy between the bladder and sphincter was noted in 11%. In a meta-analysis of all published reports of urodynamic findings in children with cerebral palsy, detrusor overactivity was seen in 80%, dyssynergy between the bladder and sphincter in 5%, and normal function in only 12% (Decter et al, 1987; Mayo and Burns, 1990; Reid et al, 1993; Bross et al, 2004; Karaman et al, 2005). From these reports it is apparent that urodynamic studies can be very revealing in all children, whether they have urinary symptoms (Bross et al, 2004), but are especially useful if frequent toileting or initial anticholinergic treatment fails to improve incontinence, the child develops urinary infection, or renal ultrasonography reveals hydronephrosis. Upper urinary tract imaging is usually normal even in children with upper motor neuron lesions (Brodak et al, 1994).

Traumatic Injuries to the Spine

Diagnosis

Despite increased exposure to and the potential for traumatic spinal cord injuries, such injuries are rarely encountered in children. The incidence in Sweden is 2.6 cases per million children per year (Augutis and Levi, 2003). The incidence tends to increase geometrically with age (Anderson and Schutt, 1980) (Fig. 128–22). When an injury does occur, it is more likely to happen in a male than a female child, and it is usually the result of a motor vehicle or bicycle accident (24% to 52%), a fall from a high place, a gunshot wound, or a diving or sports incident (Cass et al, 1984; Hadley et al, 1988; Decter and Bauer, 1993; Brown et al, 2001; Augutis and Levi 2003; Cirak et al, 2004). The type of causative injuries varies with age, with infants more prone to an injury from a motor vehicle accident (71%), toddlers and children injured secondary to a fall (48% and 34%, respectively) and adolescents having a sports-related event (29%) (Cirak et al, 2004). An injury may also occur iatrogenically after surgery to correct scoliosis, kyphosis, or other intraspinal processes or congenital aortic anomalies or after ligation of a patent ductus arteriosus (Cass et al, 1984; Batista et al, 1995). Neonates are particularly prone to a hyperextension injury during a high forceps delivery (Adams et al, 1988; Lanska et al, 1990). Among younger children, girls are affected as often as boys (Ruge et al, 1988).

Pathogenesis

Spinal cord injuries in children are intrinsically different from those in adults because of a variety of factors, including the mechanism of injury and the difference in configuration of the brainstem and spinal cord in children compared with adults. In addition, the horizontal versus vertical orientation of the facet joints in vertebral bodies that predisposes to anteroposterior subluxation in children, the delayed supportive effect of the paraspinous musculature and ligaments, and the relative heaviness of the head, which causes a fulcrum of maximal flexion of the upper cervical region in infants and young children, all contribute to a high degree of hypermobility that places the child’s spinal cord at risk for ischemic necrosis (Decter and Bauer, 1993).

Findings

The lower urinary tract dysfunction that ensues is not likely to be an isolated event but is usually associated with loss of sensation and paralysis of the lower limbs. Radiologic investigation of the spine may not reveal any bony abnormality, although momentary subluxation of osseous structures resulting from the elasticity of the vertebral ligaments can result in a neurologic injury (Pollack et al, 1988). This condition has been seen only in children (usually younger than 8 years old) and has been labeled spinal cord injury without radiologic abnormality (SCIWORA) (Pang and Wilberger, 1982; Pang and Pollack, 1989). Overall, SCIWORA can account for up to 38% of spinal cord injuries in children (Brown et al, 2001). Myelography and computed tomography show swelling of the cord below the level of the lesion (Adams et al, 1988; Lanska et al, 1990). Often, what appears to be a permanent lesion initially turns out to be a transient phenomenon with time. Although sensation and motor function in the lower extremities may be restored relatively quickly, the dysfunction involving the bladder and rectum may persist considerably longer.

During the acute phase of the injury the bladder is often acontractile and the urethral sphincter nonreactive, although normal-appearing bioelectric potentials can be recorded on sphincter EMG (spinal shock). Over a variable period of time, detrusor contractility and sphincter reactivity return as spinal cord edema subsides. With this return of function, an overactive detrusor and bladder-sphincter dyssynergy develop if the lateral reticulospinal cord pathways to and from the brainstem have been disrupted. When the lesion affects the cauda equina there is probably little to no return of bladder or urethral sphincter function. Sacral sensation and peripheral reflexes are not good indicators of ultimate lower urinary tract function (Shenot et al, 1998). Over time, the predominant urodynamic pattern in patients with a thoracic-level lesion is an overactive detrusor with DSD, high voiding pressures, eventual hydronephrosis, and vesicoureteral reflux. Often children exhibit a highly compliant bladder for a portion of bladder filling but then have C-fiber–mediated, small, ineffective rhythmic contractions of the detrusor with simultaneous waxing and waning of external urethral sphincter activity. Some urinary leakage may occur with these contractions, but in general the bladder does not empty with them. Patients with an upper thoracic or cervical lesion are likely to exhibit autonomic dysreflexia with a spontaneous discharge of α1-stimulants during bladder filling and with contractions of the detrusor. Monitoring of blood pressure and availability of α-antagonists are mandatory during VCUG or urodynamic studies (Perkash, 1997; Vaidyanathan et al, 1998b).

Management

If urinary retention occurs immediately after the injury, an indwelling Foley catheter is passed into the bladder and left in place for as short a time as possible, until the patient’s condition is stable and aseptic intermittent catheterization can be started safely on a regular basis (Guttmann and Frankel, 1966; Barkin et al, 1983). There is no difference in the incidence of urinary infection or in the development of stones in patients using sterile versus clean catheterization techniques to empty the bladder (Prieto-Fingerhut et al, 1997; VanHala et al, 1997). Rates of infection range as high as 60% to 80% (Biering-Sorensen et al, 1999), and stone formation occurs in 1.5% to 3% within the first 5 years after the trauma (Donnellan and Bolton, 1999; McKinley et al, 1999). When the child starts to void again, the timing of catheterization can be regulated so that it is used as a means of measuring the residual urine after a spontaneous void. Residual urine volumes of 25 mL or less are considered safe enough to allow reducing the frequency or even stopping the catheterization program (Barkin et al, 1983). After 4 to 6 weeks, if there is no improvement in lower urinary tract function, urodynamic studies are conducted to determine whether the condition is the result of spinal shock or an actual nerve root or spinal cord injury. An acontractile detrusor is not uncommon under these circumstances (Iwatsubo et al, 1985). On the other hand, EMG recording of the sphincter often reveals normal motor units without fibrillation potentials but absent sacral reflexes and a nonrelaxing sphincter with bladder filling, a sign that transient spinal shock has occurred (Iwatsubo et al, 1985). The outcome of this situation is guarded but good, because most cases resolve completely as edema of the cord in response to the injury subsides, leaving no permanent damage (Iwatsubo et al, 1985; Fanciullacci et al, 1988).

If and when bladder function returns and emptying is incomplete, it has been shown in the cat (Xiao et al, 1999) that peripheral L7 dermatome stimulation initiates a micturition reflex without DSD. In a preliminary study of 15 adults with spinal cord injury, detrusor overactivity, and DSD, the creation of an artificial somatic/CNS/autonomic reflex pathway resulted in satisfactory bladder control in 67% of patients. Follow-up urodynamic study revealed a change to almost normal storage and synergic voiding without DSD (Xiao et al, 2003). A more recent study showed satisfactory bladder control in 75% of patients with complete suprasacral spinal cord injury within 6 to 12 months. However, the mean and median time since the injury was 9 months, so the time from injury may have been a factor in this study (Lin et al, 2009). Incomplete emptying may be enhanced by the judicious use of α-sympatholytic agents (Al-Ali et al, 1999). The goal is balanced voiding at pressures lower than 40 cm H2O, which reduces the 30% risk for urinary tract deterioration seen in poorly managed patients (Giannantoni et al, 1998; Kim et al, 1998). If this cannot be achieved, then CIC is continued. Anticholinergics, either orally or intravesically (Vaidyanathan et al, 1998a; Wein, 1998), or capsaicin (an inhibitor of C-fiber stimulation [Wiart et al, 1998]) have been added and are effective in reducing an overactive detrusor, but at the cost of significant side effects. Alternative treatments that have been effective to ensure complete emptying at low pressure include external urethral sphincterotomy (Kim et al, 1998), urethral stent placement (Chancellor et al, 1999), or injection of botulinum-A toxin into the external sphincter (Schurch et al, 1997, 2000; Kuo, 2003; Tai et al, 2005). In some cases, a continent catheterizable abdominal urinary stoma may be created to facilitate self-catheterization in patients with low cervical or upper thoracic lesions who cannot easily catheterize themselves, in order to minimize the embarrassment of periodic genital organ exposure when care providers need to repeatedly catheterize the bladder (Sylora et al, 1997).

Recommendations

Most permanent traumatic injuries involve either the upper thoracic or the cervical spinal cord but some affect the cauda equina region. The sacral cord injury most likely produces a lower motor neuron deficit of the striated urethral sphincter that usually leads to low pressure bladder emptying with little risk of upper urinary tract deterioration. However, it probably necessitates medical and/or surgical therapy to achieve continence. On the other hand, upper spinal cord injuries produce an upper motor neuron type lesion with an overactive detrusor and DSD. The potential danger from this outflow obstruction is obvious (Donnelly et al, 1972). Substantial residual urine volumes, high-pressure reflux, urinary infections, and their sequelae are the leading causes of long-term morbidity and mortality in patients with spinal cord injury (Giannantoni et al, 1998). Even patients who voluntarily urinate and are continent or who involuntarily but spontaneously void to completion are not immune to urinary tract changes (Decter and Bauer, 1993). Urodynamic studies are imperative to identify which patients are at risk (Barkin et al, 1983). These studies should be performed within 2 to 3 months after the injury, again 6 to 9 months later, and possibly at 2 years after the trauma to determine the stability of lower urinary tract function, the need for continued CIC, and whether adjuvant drug or surgical therapy should be added (or continued) to achieve good long-term success. When these measures are employed judiciously, effective management can be achieved (Pannek et al, 1997). Renal ultrasonography early in the course and VCUG if signs of bladder outlet obstruction are present on urodynamic testing or if recurrent urinary infection ensues are also recommended. Radionuclide cystography is indicated if the patient has repeated urinary tract infection or develops hydronephrosis (Phillips et al, 1997). Because stone formation can be insidious, periodic imaging of the kidneys and bladder is necessary. Early identification and proper management may prevent the signs and effects of bladder outlet obstruction before they become apparent on radiographic examination of the urinary tract (Pearman, 1976; Ogawa et al, 1988; Watanabe et al, 1996).

Suggested Readings

Bauer SB, Colodny AH, Retik AB. The management of vesico-ureteral reflux in children with myelodysplasia. J Urol. 1982;128:102.

Bauer SB, Hallet M, Khoshbin S, et al. The predictive value of urodynamic evaluation in the newborn with myelodysplasia. JAMA. 1984;152:650.

Blaivas JG, Labib KB, Bauer SB, Retik AB. A new approach to electromyography of the external urethral sphincter. J Urol. 1977;117:773.

Edelstein RA, Bauer SB, Kelly MD, et al. The long-term urologic response of neonates with myelodysplasia treated proactively with intermittent catheterization and anticholinergic therapy. J Urol. 1995;154:1500.

Guzman L, Bauer SB, Hallet M, et al. The evaluation and management of children with sacral agenesis. Urology. 1983;23:506.

Kaefer M, Pabby A, Kelly M, et al. Improved bladder function after prophylactic treatment of the high risk neurogenic bladder in newborns with myelomeningocele. J Urol. 1999;162:1068-1071.

Kaefer M, Rosen A, Darbey M, et al. Pressure at residual volume: a useful adjunct to standard fill cystometry. J Urol. 1997;158:1268-1271.

Lapides J, Diokno AC, Silber SJ, Lowe BS. Clean intermittent self-catheterization in the treatment of urinary tract disease. J Urol. 1972;107:458.

McGuire EJ, Woodside JR, Borden TA, Weiss RM. The prognostic value of urodynamic testing in myelodysplastic patients. J Urol. 1981;126:205.

Mitrofanoff P. Cystometric continente trans-appendiculaire dans le traitement de vessies neurologiques. Chir Pediatr. 1980;21:297.

Palmer LS, Richards I, Kaplan WE. Age related bladder capacity and bladder capacity growth in children with myelomeningocele. J Urol. 1997;158:1261-1264.

Satar N, Bauer SB, Scott RM, et al. Late effects of early surgery on lipoma and lipomeningocele in children less than two years old. J Urol. 1997;157:1434-1437.

Spindel MR, Bauer SB, Dyro FM, et al. The changing neuro-urologic lesion in myelodysplasia. JAMA. 1987;258:1630.

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Sacral Agenesis

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Imperforate Anus

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Cerebral Palsy

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Bross S, Pomer S, Doderlein L, et al. Urodynamic findings in patients with infantile cerebral palsy. Aktuelle Urol. 2004;35:54.

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Traumatic Injuries to the Spine

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Wiart L, Joseph PA, Petit H, et al. The effects of capsaicin on the neurogenic hyper-reflexic detrusor: a double blind placebo controlled study in patients with spinal cord disease: preliminary results. Spinal Cord. 1998;36:95-99.

Xiao CG, deGroat WC, Godec CJ, et al. “Skin-CNS-bladder” reflex pathway for micturition after spinal cord injury and its underlying mechanisms. J Urol. 1999;162:936-942.

Xiao CG, Du MX, Dai C, et al. An artificial somatic-central nervous system-autonomic reflex pathway for controllable micturition after spinal cord injury: preliminary results in 15 patients. J Urol. 2003;170(4 Pt. 1):1237-1241.