Myelodysplasia and Neurogenic Bladder Dysfunction 

Updated: Jul 09, 2019
Author: Terry F Favazza, MD; Chief Editor: Marc Cendron, MD 

Overview

Background

The term myelodysplasia includes a group of developmental anomalies that result from defects that occur during neural tube closure. Lesions may include spina bifida occulta, meningocele, lipomyelomeningocele, or myelomeningocele. Myelomeningocele is by far the most common defect seen and is the most devastating. This article focuses on identifying neurogenic bladder dysfunction, defining treatment options, and outlining follow-up care in children with myelodysplasia.

Pathophysiology

Spinal cord and vertebra formation begin at approximately 18 days' gestation. Closure of the spinal canal begins at the cephalad end, proceeds caudally, and is complete by 35 days' gestation. The exact cause of neurospinal dysraphism is unknown, but it appears to be multifactorial. Genetic, environmental, and nutritional factors have been implicated; however, no specific etiology has been pinpointed.

An increased frequency of neural tube defects appears to occur in the offspring of mothers who had folic acid deficiency during pregnancy. Based on these data, the current recommended daily allowance (RDA) of 400 μg/day of folic acid was established for women during pregnancy.

Spina bifida is a broad term that may be used to describe a number of open defects of the spinal column. A meningocele occurs when the meningeal sac (the sac that envelops the spinal cord) extends beyond the confines of the vertebral canal but does not contain any neural elements. A myelomeningocele occurs when neural tissue (nerve roots, spinal cord tissue, or both) is included in the sac. A lipomyelomeningocele is defined by the presence of fatty tissue and neural elements within the sac.

Myelomeningoceles account for 90% of open spinal dysraphic states. The overwhelming majority of myelomeningoceles are directed posteriorly, with most defects involving the lumbar vertebrae. In decreasing order of frequency, sacral, thoracic, and cervical vertebrae are affected. In the rare case of an anteriorly directed defect, the sacral vertebrae are most commonly involved.

An Arnold-Chiari malformation is associated in 65-85% of children with a myelomeningocele.[1] This occurs when the cerebellar tonsils herniate through the foramen magnum and obstruct the fourth ventricle, which prevents cerebrospinal fluid (CSF) from entering the subarachnoid space. These children require shunting of the ventricles, most commonly to the peritoneum. A small number (~5%) of patients with myelomeningoceles do not have a neurogenic bladder, but this is the exception.

Congenital defects of spinal column formation that are not open defects are often termed spina bifida occulta. The lesions can be subtle, often with no obvious signs of motor or sensory denervation; however, in many patients, a cutaneous abnormality can be seen overlying the lower spine. This can vary from a dimple or a skin tag to a tuft of hair, a dermal vascular malformation, or an obvious subdermal lipoma.

Alterations may be found in the arrangement or configuration of the toes, along with discrepancies in lower extremity muscle size and strength, weakness, or abnormal gait. Back pain and an absence of perineal sensation are common symptoms in older children. The frequency of abnormal lower urinary tract function in patients with spina bifida occulta has been reported to be as high as 40%.

Sacral agenesis, defined as the absence of two or more lower vertebral bodies, is another defect that can produce voiding dysfunction. Because perineal sensation is usually intact and lower-extremity function is normal, the only clue is often a flattened buttock and a short gluteal cleft. However, in many patients, no external signs are evident. If suspected, diagnosis is made using a lateral film of the lower spine. Even at best, only 50% of affected infants are identified in the newborn period.

The neurologic lesion produced by the dysraphism can vary widely, depending on the neural elements that have everted with the meningocele sac. The bony vertebral level correlates poorly with the neurologic lesion produced.

Additionally, different growth rates between the vertebral bodies and the elongating spinal cord can introduce a dynamic factor to the lesion. Fibrosis may surround the cord at the site of meningocele closure, and the cord can become tethered during growth. This can lead to changes in bowel, bladder, and lower-extremity function. If these are noted, investigation is warranted to exclude cord tethering.

Etiology

The exact cause of dysraphism is unknown, but many factors appear to be involved. Genetic, environmental, and nutritional factors have been implicated, though no specific etiology has been pinpointed.

Genetic

If myelodysplasia is present in one child in a family, the chance of having a second child with the same condition is 2-5%. The prevalence of myelodysplasia is increased in children born to mothers older than 30 years. 

In a 2019 study, whole-exome sequencing identified four loss‐of‐function variants in three genes associated with neural tube defects: MTHFR, DLC1, and ITGB1.[2]

Environmental

Studies of open in-vivo neural tube defects indicate that the exposed tissue in the myelomeningocele sustains secondary injury from mechanical and chemical factors during its prolonged exposure to the uterine environment. The additive effects of the congenital defect and the superimposed trauma appear to combine to determine the total neurologic deficit displayed by the infant.

Nutritional

Prevalence of neural tube defects appears to be increased in the offspring of mothers who had folic acid deficiency during pregnancy. On the basis of these data, the current RDA of 400 μg/day of folic acid was established for women during pregnancy.

Diabetes

Sacral agenesis appears to be associated with diabetes—specifically, with the presence of insulin during fetal development. Maternal diabetes mellitus is seen in 12-18% of patients with sacral agenesis, and 1% of children born to mothers who are insulin-dependent have the condition. Although the mechanism is unknown, the defect has been reproduced when chick embryos are exposed to insulin.

Epidemiology

Old Content

United States statistics

The reported prevalence of spinal dysraphism in the United States is 1 case per 1000 live births.[3] For unknown reasons, spinal dysraphism is more common in the eastern United States. Studies conflict regarding whether a seasonal variation occurs in prevalence. A genetic component to the disease appears to be present; if spinal dysraphism is present in one child, the chance of having a second child with the same condition is 2-5%. In addition, prevalence is increased in children born to mothers older than 30 years.

Spina bifida is the most common permanently disabling birth defect in the United States, affecting about one out of every 1400 to 1500 newborns.[4] Each year, about 1645 babies are born with spina bifida in the United States.[5]  The Spina Bifida Association has conservatively estimated that there are 70,000 people in the United States living with this condition. At present, its prevalence appears to be decreasing, in part because of preventive measures followed by expectant mothers before and during pregnancy, as well as prenatal testing.[4]

The prevalence of spina bifida occulta (myelodysplasia with a closed vertebral canal) is 1 case per 4000 live births. Prevalence of sacral agenesis in children of mothers with insulin-dependent diabetes mellitus is higher than average (1%).

International statistics

A large range in prevalence has been recorded internationally. Studies have demonstrated rates ranging from 0.12 to 4.5 cases per 1000 live births. The prevalence of spinal dysraphism appears to be lower in Asian countries.

Age-related demographics

Myelodysplasia can be detected before birth by means of antenatal ultrasonography (US). If myelodysplasia is detected antenatally, cesarean delivery may improve neurologic function by reducing the trauma caused by vaginal delivery. Neural tube defects can be suspected if amniocentesis shows increased levels of alpha-fetoprotein, but these results can be misleading, with large numbers of both false-positive and false-negative results.

In many infants, myelodysplasia is detected immediately at birth; however, spina bifida occulta may not become apparent until later in life, and voiding dysfunction may be the only sign of occult disease.

Sex-related demographics

Myelodysplasia is more common in females than in males.

Race-related demographics

A study from California demonstrated a slightly higher prevalence in children born to Hispanic mothers.[6]  White mothers were the second most likely to have children with myelodysplasia, followed by black and Asian mothers.

In a study that used data from 12 state-based birth defects tracking programs from 1997-2007 to estimate the total number of pregnancies affected by spina bifida as compared with the total number of live births (ie, the prevalence of spina bifida), Hispanic women were found to be more likely to have a child affected by spina bifida than either non-Hispanic white women or non-Hispanic black womenwere.[5] Figures for each racial/ethnic group were as follows:

  • Hispanic - 3.80 per 10,000 live births
  • Non-Hispanic black or African American - 2.73 per 10,000 live births
  • Non-Hispanic white - 3.09 per 10,000 live births

Prognosis

The prognosis for patients with myelodysplasia has improved dramatically over the past decades. Neurosurgical techniques and antibiotics have improved, and far fewer infants die of CNS infections and complications related to closure of the defect.

Since the introduction of intermittent catheterization (IC), incontinent urinary diversion is no longer performed with the same frequency as in the past, with the result that operative morbidity and mortality have been greatly reduced. Many patients can be treated with clean IC (CIC) alone or with adjunctive pharmacotherapy, without ever requiring surgery.

In selected patients, bladder augmentation and continence surgery may provide medical benefits and an improvement in the patient's quality of life.

Patient Education

Starting at birth and as the patient ages, parents and patients need to be educated regarding the many issues associated with living with myelodysplasia.

Teach parents and patients the skills of catheterization, how to recognize infection, the need to alleviate constipation, the importance of watching for changes in symptoms, and the facts regarding sexual issues. Constantly remind parents and patients of the need to adapt to new problems and the need for lifelong observation by health care providers. When patients are able to become involved in their own care, encourage them to do so, because eventually they will be responsible for looking after themselves.

Sexuality, though not an issue in childhood, becomes a progressively more important concern as the patient ages. It has historically been ignored in individuals with myelodysplasia; nevertheless, patients with myelodysplasia have sexual encounters, and studies indicate that at least 15-20% of males are capable of fathering children and that 70% of females can conceive and carry a pregnancy to term.

Additionally, although puberty in boys with myelodysplasia appears to occur at the same age as puberty in healthy boys, menarche can begin 2 years earlier than usual in girls.

For these reasons, counseling patients in early adolescence regarding sexual development is important.

 

Presentation

History

Obtain a birth history from the parents. Asking about any difficulties with pregnancy or delivery is important, as is obtaining a history of spinal dysraphism in either parent, their families, or siblings.

When myelodysplasia is present, observe the voiding patterns of the child and gather a specific voiding history from caregivers. Admittedly, this may be difficult in newborns.

Pay attention to the presence of straining, the force and caliber of the urinary stream, dry diaper intervals, a history of urinary tract infections (UTIs), and attempted treatments (if any).

Often, the urologist sees the newborn before discharge from the hospital, either before or after closure of the spinal defect, and voiding habits may not be known. In this setting, check postvoiding residual volumes, and if they are elevated, institute the use of intermittent catheterization (IC) or an indwelling catheter in the perioperative period.

Physical Examination

The open myelodysplastic defect is obvious, and contents of the sac can often be detected within the membrane, helping to establish the diagnosis. If the patient is stable, closure of the spinal defect usually takes precedence over other issues. Once closure is complete, a full physical examination is necessary.

Search for any other abnormalities and assess neurologic function. Careful inspection of the genitalia is necessary to evaluate for any ambiguities regarding the sex of the child and to look for hypospadias and cryptorchidism in males. Pay attention to the abdominal musculature, lower-extremity function, anal sphincter tone, and the presence of a sacral reflex arc (bulbocavernosus reflex), which is tested for by gently squeezing the penis or clitoris and watching for an anal wink.

Additionally, during the abdominal examination, attempt to assess renal size and the presence and degree of bladder distention. In patients who require ventriculoperitoneal (VP) shunting, communicating hydroceles and hernias must be identified for surgical correction.

If the child is apparently unable to spontaneously empty the bladder, the use of IC is initiated. The expected bladder capacity of the newborn is 10-15 mL, and residual volume should be less than 5 mL. The definitive examination of bladder function is a urodynamic study (see Other Tests).

Although physical examination focuses on looking for other anomalies and assessing neurologic function in patients with open defects, the presence of skin discoloration, a mole, a tuft of hair, or a dimple may be the only sign of underlying spinal defect in patients with occult dysraphic states. Evaluate these children with the appropriate imaging studies and a urodynamic study to define the defects (see Workup).

Complications

The meningocele sac is often nothing more than a very thin transparent tissue that may be open and leaking cerebrospinal fluid (CSF). This is a potential source of central nervous system (CNS) infection, which can lead to death if untreated in the perinatal period. Prompt closure of the defect is imperative. The closure itself producing neurologic symptoms is a concern, but this appears to happen in fewer than 5% of patients.

Urologic morbidity in patients with myelodysplasia is significant. Myelodysplasia can contribute to voiding dysfunction, UTIs, vesicoureteral reflux (VUR), and renal scarring. Surgery may be required to establish adequate bladder drainage. If not managed appropriately, myelodysplasia can cause significant urologic problems that can potentially lead to progressive renal failure, necessitating dialysis or transplantation.

UTIs are common in infants with myelodysplasia, and patients must be promptly treated when recognized. Recurrent infections, especially those associated with a poorly compliant bladder and VUR, can lead to pyelonephritis, renal scarring, and an eventual loss of renal function.[7]  In the absence of reflux, patients with infections are usually treated symptomatically, but in children who experience recurrent infections, prophylactic treatment can be instituted.

VUR occurs in 3-5% of infants with myelodysplasia and is usually associated with detrusor hyperreflexia or dyssynergia. If the neurogenic bladder remains untreated, the incidence of VUR increases with time until, by age 5 years, 30-40% of children are affected.

Treatment of VUR consists of antibiotic prophylaxis to prevent infection, anticholinergic medications to lower detrusor filling pressures, and use of a method to empty the bladder (most commonly, IC). In the most severe cases of reflux or if evidence of progressive renal scarring is apparent, surgery can be performed to lower bladder storage pressures or to provide an antireflux mechanism.

Renal damage or failure can occur as a product of repeated infections with progressive renal scarring and damage or as a result of obstruction caused by inability to empty the bladder. This can occur slowly over a period of years or with surprising rapidity, underscoring the need for regular lifelong follow-up care in patients with myelodysplasia. Even with maximal medical and surgical therapies, renal failure can occur (albeit rarely), and dialysis or transplantation may be needed.

 

DDx

Diagnostic Considerations

Other problems to be considered include the following:

  • Spina bifida occulta
  • Sacral agenesis
  • Nonneurogenic/neurogenic bladder
  • Vesicoureteral reflux

Differential Diagnoses

 

Workup

Laboratory Studies

Obtain urinalysis, urine culture, and serum electrolytes with blood urea nitrogen (BUN) and creatinine levels before the infant leaves the hospital. BUN and creatinine levels should be tested at least 24 hours after birth to reflect the infant's levels rather than the mother's.

Imaging Studies

Abdominal ultrasonography

Perform abdominal ultrasonography (US) as soon as possible after birth to detect hydronephrosis or other upper genitourinary (GU) tract pathology. Once the child has recovered from the closure of the spinal defect and is stable for transportation, renal US is performed to evaluate upper GU tract anatomy.

Voiding cystourethrography

After US, voiding cystourethrography (VCUG) is performed to evaluate the lower GU tract. These studies provide a baseline for the appearance of the upper and lower GU tracts, can facilitate the diagnosis of hydronephrosis or vesicoureteral reflux (VUR), and can help identify children at risk for upper GU tract deterioration.

VCUG is the radiographic test of choice to evaluate for VUR. The procedure is as follows:

  • A supine film of the abdomen is obtained first, including the bladder and kidneys
  • A small catheter is placed in the child's bladder, and the bladder is filled with contrast
  • A cystogram is obtained with the patient in the supine and oblique positions; the size, shape, and capacity of the bladder are evaluated, as is the presence of trabeculae or diverticula.
  • The next film is obtained as the child voids or leaks; when VUR is present, the bladder, urethra, and ureters are demonstrated; in higher-grade reflux, the renal collecting system also may be seen
  • A final film is obtained after the bladder has been emptied; the presence of reflux is an indication for starting prophylactic antibiotics

Lateral spine radiography

In suspected sacral agenesis, a lateral spine film is the appropriate imaging study.

Magnetic resonance imaging

Although US of the spinal canal can be useful in infants younger than 5 months, it becomes much less sensitive once the vertebrae begin to ossify. The criterion standard for evaluation of spinal cord anatomy is magnetic resonance imaging (MRI). This is the test of choice when a change in neurologic symptoms causes cord tethering to be suspected.

Other Tests

Measure of residual urine

As soon as possible, measure the residual urine to determine if intermittent catheterization (IC) is necessary. The normal capacity of the newborn bladder is 10-15 mL, and consistent catheterized residual volumes of 10 mL or more should raise concerns regarding detrusor areflexia.

Urodynamic study

This test provides the most information regarding the impact of myelodysplasia on bladder function and is used to assess bladder function and guide treatment. Because the bony level often does not always correspond with the neurologic defect that is present, and because the effect of the lesion on bladder function cannot be entirely determined by radiographic studies or physical examination, the information gained from a urodynamic study is invaluable.

The urodynamic study provides a measurement of several variables related to bladder function. Bladder capacity, compliance, detrusor and abdominal storage, voiding pressures, urine flow rate, postvoiding residual volume, and the relationship between detrusor contraction and the urinary sphincter can be evaluated. In addition, if contrast is instilled in the bladder, the anatomy can be imaged during voiding.

The core of the urodynamic study is cystometrography (CMG). A small catheter is placed in the bladder, and the bladder is slowly filled with liquid. Pressures within the bladder (intravesical) and the abdominal compartment are measured, and by subtracting the abdominal pressure from the intravesical pressure, the pressure generated by the detrusor muscle can be calculated. Because the child is monitored through a filling and voiding phase, bladder capacity can be quantified, and the urine flow rate, postvoiding residual volume, and the force generated by a bladder contraction can be measured.

Electromyography

If more information is desired, electromyography (EMG) can be used to demonstrate the relation between the detrusor muscle and the external urinary sphincter.

During normal voiding, the sphincter relaxes as the detrusor contracts to allow unobstructed urinary flow. Spinal cord injury can lead to discoordination so that the sphincter is closed when the detrusor contracts, creating high pressures within the bladder but low flow rates. This is known as detrusor-sphincter dyssynergy. In infants with detrusor-sphincter dyssynergy, increased EMG activity occurs during voiding. The presence of this dyssynergy places infants at a much greater risk of upper GU tract deterioration.

Fluoroscopy

Fluoroscopy can be used to perform video-urodynamic imaging with contrast enhancement of the bladder, which allows the bladder to be depicted during voiding. In addition, reflux may be revealed (identical to findings in VCUG), or if a closed sphincter is revealed during voiding, findings strongly suggest the presence of detrusor-sphincter dyssynergy, often obviating the need for EMG studies.

Remember that a great number of artifacts can be introduced into urodynamic studies when they are performed in infants and children.

Comparison of adjunctive data from radiographic studies and voiding or catheterized volume diaries is always advisable during planning of individualized bladder management.

Common findings are as follows:

  • A common diagnosis made using urodynamic studies is detrusor areflexia or a bladder that does not generate a contraction; the result is that the bladder will not empty (stasis); these patients can occasionally void with abdominal straining, but except in rare cases, they need to be managed with IC
  • Another possible diagnosis is detrusor-sphincter dyssynergy, in which increased sphincter activity occurs during detrusor contraction; this finding is important because DSD has been associated with an increased risk of upper GU tract deterioration in as many as 70% of patients; it is typically managed with IC and anticholinergic medications
  • In older patients, sphincterotomy (surgical ablation of the urinary sphincter) can be considered, but this procedure dramatically reduces outlet resistance and usually renders patients incontinent and reliant on an external collection device
  • Detrusor hyperreflexia, defined as the presence of involuntary detrusor contractions (usually at low volumes), can produce symptoms of urgency and urge incontinence; treatment is composed of anticholinergic medications to reduce contractions and timed voiding or use of IC
  • Urodynamic studies can also reveal outflow obstruction; in patients with obstruction, high voiding and/or storage pressures are seen, which have been correlated with increased risk of upper GU tract deterioration; this is managed with IC, surgical resection of the obstructing tissue, or urinary diversion (in extreme cases)

Genetic testing

If multiple anomalies are present, if the sex of the child is in question, or if a specific genetic syndrome is suspected, a karyotype may be of value but is not routinely required.

 

Treatment

Medical Care

Medical care of children with myelodysplasia who have a neurogenic bladder requires constant vigilance and adaptation to new problems. Therapy is based on a few basic goals, as follows:

  • To ensure safe intravesical pressures
  • To prevent urinary stasis and urinary tract infections (UTIs)
  • To promote urinary continence

The ultimate goal of medical therapy is to preserve renal function. In older children, medication may help maintain continence.

Infection

UTIs are common in children with myelodysplasia. Antibiotics are used when indicated to treat acute infections. In the absence of reflux, patients with UTIs are treated symptomatically. Patients with vesicoureteral reflux (VUR) are often placed on prophylactic antibiotics to reduce the chance of upper UTI or pyelonephritis. Bacteriuria is seen in as many as 55% of individuals who have received clean intermittent catheterization (CIC). Patients who are completely asymptomatic do not need treatment.

Reflux

Reflux occurs in 3-5% of infants with myelodysplasia and is usually associated with detrusor hyperreflexia or detrusor-sphincter dyssynergy.

Treatment consists of antibiotic prophylaxis to prevent infection, anticholinergic medications to lower detrusor filling and voiding pressures, and a method of bladder emptying (most commonly, CIC). In children with lower-grade reflux who empty their bladders completely, treatment may be limited to prophylactic antibiotics. In children with high-grade reflux, CIC is started to ensure complete emptying.

Children who are unable to empty their bladders, regardless of reflux, are treated with CIC (see below). Children with detrusor hyperreflexia (with or without hydronephrosis) are started on anticholinergic therapy to decrease intravesical pressures and possibly decompress the upper genitourinary (GU) tract. Reflux treated in this manner has shown a dramatic response, resolving in 30-55% of children. Avoid the Crede maneuver (voiding by suprapubic pressure) in children with reflux, because it can increase pressures and aggravate the degree of reflux.

Inability to empty bladder

Because most patients with myelodysplasia are unable to empty their bladders spontaneously, numerous methods have been devised to potentiate bladder emptying. Initially, large numbers of patients underwent urinary diversion; however, the frequency of renal failure was substantial. This changed dramatically with the introduction of CIC.

Bladder catheterization on a regular basis is a safe, effective method of emptying the bladder and, if performed under clean conditions, does not appear to significantly increase the risk of infection. More than any single concept, the practice of CIC has changed the treatment of and approach to patients with neurogenic bladders.[8]

Currently, urinary diversion is rarely performed in pediatric patients.

Incontinence

Although not an issue in infancy, continence becomes more important as patients age. When children reach school age and social interactions increase, managing incontinence becomes a larger priority.

Medical therapy consists of anticholinergic medications to increase the functional bladder volume and to reduce involuntary and uninhibited bladder contractions. This serves to decrease urgency and incontinence and potentially to increase the bladder's functional storage capacity.

Additionally, alpha agonists have been used infrequently in children to increase sphincter tone at the bladder neck, initiating a state of urinary retention in an effort to decrease incontinence. Thus far, the therapy has had limited use in patients with myelodysplasia.

Studies have reported the use of botulinum toxin directly injected into the detrusor of children with myelodysplasia as being successful in treating incontinence.[9, 10, 11, 12, 13, 14]  However, this treatment is not yet widely used.

Impaired bowel function

Often, children with myelodysplasia have disturbances of bowel as well as urinary function. This is managed most commonly with mild laxatives, such as mineral oil, combined with enemas or digital stimulation to facilitate removal of bowel contents.

Constipation can affect bladder emptying adversely via a mechanism that is not yet fully understood but is likely to be related to altered tone of the pelvic floor musculature or the physical compression of hard stool distorting the geometry of the bladder. The need for a program to combat constipation by maintaining soft stools and facilitating complete evacuation of bowel contents is an integral part of treatment in children with myelodysplasia.

Special concerns

A remarkable number (in some studies, as many as 45%) of patients with myelodysplasia develop hypersensitivity to latex, a phenomenon believed to be related to recurrent exposure of peritoneal and mucosal surfaces to medical devices containing latex throughout childhood. Reactions range from contact dermatitis to anaphylaxis and cardiovascular collapse.

Consider all patients with myelodysplasia of spina bifida to have a latex allergy, and make every effort to avoid exposure to latex from birth. Gloves, catheters, crib pads, and bottle nipples are all potential sources and may exacerbate hypersensitivity.

Surgical Care

Surgery for neurogenic bladder, though once performed on most patients, is now primarily reserved for patients who have progressive renal damage despite maximal medical therapy, those with extremely noncompliant bladders, or those who wish to improve their continence.

Most procedures are designed to allow adequate low-pressure bladder storage (thereby protecting the upper GU tract), to correct persistent reflux and prevent renal scarring, or to aid with continence. Experimental intrauterine fetal surgery performed to limit future morbidity is under investigation at some centers.[15, 16, 17, 18]

Intrauterine surgery

Studies of surgically created neural tube defects in rats demonstrate that the exposed tissue in the myelomeningocele sustains secondary injury from mechanical and chemical factors during its prolonged exposure to the uterine environment. This has led to research on the effects of in-utero closure of the defect.

Although intrauterine closure is considered experimental because of the limited numbers performed, preliminary findings appear to indicate that it can be accomplished with minimal morbidity to the fetus and the mother and that it may decrease the need for ventriculoperitoneal (VP) shunting later in life.

Whether in-utero repair improves the neurologic outcome in these patients remains unclear.

Procedures to correct vesicoureteral reflux

Ureteral reimplantation

Ureteral reimplantation can be performed in patients who have recurrent symptomatic UTIs despite adequate bladder drainage and antibiotic prophylaxis or in patients who have persistent high-grade reflux with demonstrated renal scarring.

The purpose of the procedure is to create a nonrefluxing connection between the ureter and the bladder. Most often, the procedure is performed by tunneling the ureter beneath the detrusor muscle. This treatment is very effective, provided that a regimen is implemented to ensure a low-pressure reservoir and bladder emptying.

Dextranomer/hyaluronic acid (Deflux) injection

This is a much less invasive way to address VUR. Deflux (a viscous gel consisting of dextranomer microspheres and hyaluronic acid) is injected cystoscopically just beneath the ureteral orifice to prevent reflux. It is performed as an outpatient procedure with excellent success rates (70-85% with a single injection) and can be repeated if necessary.[19, 20]

Vesicostomy

In infants who cannot be catheterized or who demonstrate worsening renal function despite medical therapy and CIC, cutaneous vesicostomy can be performed to establish adequate bladder drainage. In this procedure, the bladder is brought out to the skin, and urine drains continually into a diaper. Vesicostomy is an effective temporary procedure that may be reversed at any time.

Bladder augmentation

Bladder augmentation is an option in patients with small bladder capacity and poor bladder compliance despite maximal medical therapy.[21]  By anastomosing a detubularized segment of bowel to the bladder, capacity can be increased and storage pressures can be lowered, minimizing upper GU tract deterioration and improving continence.

Depending on the segment of bowel used, problems with metabolic derangements, mucous production, stone formation, and hematuria can develop but usually respond to medical therapy. If incontinence is a significant problem, a bladder neck sling procedure can be performed along with bladder augmentation.

Urinary diversion and undiversion

In current practice, formal urinary diversion for neurogenic bladder is very rarely performed. The risks of major abdominal surgery, metabolic derangements, and long-term upper GU tract deterioration are present with urinary diversion. Since the advent of CIC, some patients who underwent incontinent urinary diversion as infants have undergone successful undiversion with bladder augmentation.

Procedures for incontinence

As patients grow older, continence begins to play a larger role in their lives. Several procedures have been developed to improve continence, with the hope to promote more independent living.

Dextranomer/hyaluronic acid (Deflux) bladder neck injection

This procedure consists of cystoscopically injecting dextranomer/hyaluronic acid into the bladder neck to increase outlet resistance. It has been shown to improve continence, but complete cures are unpredictable, and the durability of the procedure contineus to be evaluated.[22, 23, 24, 25, 26]

Bladder neck sling

This procedure entails placing a sling of either autologous tissue or synthetic polypropylene mesh beneath the urethra in order to increase outlet resistance. There are several variations to the procedure, but overall success rates range from 60% to greater than 85%, with a number of patients becoming fully continent.

Detrusor myoplasty

This procedure, though not commonly done, has the possibility of increasing bladder contractility in some patients. It is performed by harvesting the patient's latissimus dorsi muscle and microsurgically transplanting it so that it wraps around the bladder. This has allowed some patients to spontaneously void and reduce their dependence on catheterization.[27]

Stem cell injection

Stem cell injection remains experimental in this setting, but preliminary studies showed some promise. In this procedure, stem cells are cystoscopically injected into the urinary sphincter. The goal of therapy is to increase sphincter activity and improve continence. Animal and early human trials have been encouraging.[28]

Diet

Generally, dietary management is the first step to achieving fecal continence. Both constipation and diarrhea must be avoided. The goal is to provide enough bulk to have one bowel movement per day at a socially acceptable time. Usually, digital stimulation, suppositories, or enemas are used to regulate the timing of bowel movements.

If the child has difficulty with constipation, altering the diet to include more fiber and adding bowel lubricants (eg, mineral oil) may help regulate bowel movements. Adequate bowel and bladder management are crucial for optimizing social, school, and work activities.

In addition, because of neurologic and orthopedic issues, mobility is limited, reducing the patient's ability to exercise. These patients are at high risk for obesity.

Activity

Children with myelodysplasia often have limited development or motion of the extremities; however, no specific activity limitations are required. Children are encouraged to be as active as possible within the limitations of the defect.

Consultations

Patients with myelodysplasia have a multitude of issues that require constant observation. The following consultations may be warranted:

  • Intervention by a neurosurgeon is needed, starting at birth; patients require initial closure of the spinal defect, cerebrospinal fluid (CSF) shunting, and monitoring for cord tethering or shunt malfunction
  • Often, consultation with a neurologist is required to define defects and watch for any change in symptoms
  • If significant bone abnormalities are present, consultation with an orthopedist may be necessary
  • Parents, and eventually the child, undoubtedly need the support of a psychologist to help deal with the struggles inherent in raising a child or growing up with myelodysplasia
  • Physical therapy may also be needed

Long-Term Monitoring

General follow-up care

That patients require lifelong supervision and monitoring of renal function cannot be stressed enough. Renal failure can progress slowly or occur with startling rapidity.

Check postvoiding residual volumes every 6-12 months and renal function (blood urea nitrogen [BUN] and creatinine levels) yearly. Perform renal ultrasonography yearly. Many advocate a yearly urodynamic study for the first 5 years of life, followed by biennial evaluation. Perform a repeat urodynamic study any time the patient experiences any change in neurologic symptoms.

Tethered cord

As children age, differing growth rates of the vertebral bodies and the spinal cord can add a dynamic element to the lesion. Fibrosis surrounding the cord at the site of meningocele closure can tether it during growth. This can lead to changes in bowel, bladder, and lower-extremity function. If these are noted, evaluation with magnetic resonance imaging (MRI) is indicated. From the urologic standpoint, MRI and a repeat urodynamic study are warranted when the patient has a change in symptoms or undergoes any neurosurgical procedure.

 

Medication

Medication Summary

Pharmacologic therapy plays an integral role in the treatment of patients with neurogenic bladder dysfunction. Treatment usually centers around 3 major elements: the use of antibiotics to prevent infection, the use of anticholinergic medications to relax the bladder and (hopefully) to increase storage capacity, and the use of alpha agonists to attempt to improve continence.

Antibiotics are used when indicated to treat acute infections and, in vesicoureteral reflux, are used as prophylaxis to prevent UTIs, pyelonephritis, and renal damage. Anticholinergic medications help suppress involuntary and uninhibited bladder contractions. This decreases urgency and incontinence and increases the bladder's functional storage capacity.

The role of alpha agonists is to increase smooth muscle tone at the bladder neck, initiating a state of urinary retention in an effort to alleviate incontinence. Thus far, the use of alpha agonists has had limited use and limited success in patients with myelodysplasia.

Anticholinergic Agents

Class Summary

The major stimulus for bladder contraction is activation of the detrusor muscle via muscarinic cholinergic neuronal connections. Anticholinergic medications help suppress bladder contractions, especially involuntary and uninhibited contractions. This serves to decrease urgency and incontinence and to potentially increase the bladder's functional storage capacity.

Oxybutynin (Ditropan)

Synthetic tertiary amine that, similar to atropine, antagonizes the muscarinic actions of acetylcholine. Also has a direct spasmolytic effect on the detrusor muscle and the small intestine, as well as local anesthetic action. Reduces the incidence of uninhibited bladder contractions.

Tolterodine (Detrol)

Competitive muscarinic receptor antagonist for overactive bladder. Differs from other anticholinergic types because it is selective for the urinary bladder over salivary glands. Exhibits a high specificity for muscarinic receptors, and has minimal activity or affinity for other neurotransmitter receptors and other potential targets (eg, calcium channels).

Solifenacin succinate (VESIcare)

Elicits competitive muscarinic receptor antagonist activity, which results in anticholinergic effect and inhibition of bladder smooth muscle contraction. Indicated for overactive bladder with symptoms of urgency, frequency, and urge incontinence.

Darifenacin (Enablex)

Extended-release product eliciting competitive muscarinic receptor antagonistic activity. Reduces bladder smooth muscle contractions. Has high affinity for M3 receptors involved in bladder and GI smooth muscle contraction, saliva production, and iris sphincter function. Indicated for overactive bladder with symptoms of urge incontinence, urgency and frequency. Swallow whole; do not chew, divide, or crush.

Fesoterodine (Toviaz)

Competitive muscarinic receptor antagonist. Antagonistic effect results in decreased bladder smooth muscle contractions. Indicated for symptoms of overactive bladder (eg, urinary urge incontinence, urgency, and frequency). Available as 4- or 8-mg extended-release tab.

Trospium (Sanctura)

Quaternary ammonium compound that elicits antispasmodic and antimuscarinic effects. Antagonizes acetylcholine effect on muscarinic receptors. Parasympathetic effect reduces smooth muscle tone in the bladder. Indicated to treat symptoms of overactive bladder (eg, urinary incontinence, urgency, frequency).

Hyoscyamine (Levbid, Levsin)

Blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS, which, in turn, has antispasmodic effects.

Propantheline (Pro-Banthine)

Blocks action of acetylcholine at postganglionic parasympathetic receptor sites.

Anticholinergic Agent, Transdermal

Class Summary

The major stimulus for bladder contraction is activation of the detrusor muscle via muscarinic cholinergic neuronal connections. Anticholinergic medications help suppress bladder contractions, especially involuntary and uninhibited contractions. This serves to decrease urgency and incontinence and to potentially increase the bladder's functional storage capacity.

Oxybutynin chloride 10% gel (Gelnique)

Oxybutynin chloride is a synthetic tertiary amine that, similar to atropine, antagonizes the muscarinic actions of acetylcholine. It also has a direct spasmolytic effect on the detrusor muscle and the small intestine, as well as local anesthetic action. Oxybutynin chloride reduces the incidence of uninhibited bladder contractions.

Neuromuscular Blocker Agent, Toxin

Class Summary

BOTOX blocks neuromuscular transmission by binding to acceptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. This inhibition occurs as the neurotoxin cleaves SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings. When injected intramuscularly at therapeutic doses, BOTOX produces partial chemical denervation of the muscle, resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by BOTOX.

Following intradetrusor injection, BOTOX affects the efferent pathways of detrusor activity via inhibition of acetylcholine release. In addition, BOTOX is believed to inhibit afferent neurotransmitters and sensory pathways.

Botulinum toxin type A

BOTOX blocks neuromuscular transmission by binding to acceptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. When injected intramuscularly at therapeutic doses, BOTOX produces partial chemical denervation of the muscle, resulting in a localized reduction in muscle activity.

Following intradetrusor injection, BOTOX affects the efferent pathways of detrusor activity via inhibition of acetylcholine release. In addition, BOTOX is believed to inhibit afferent neurotransmitters and sensory pathways. It is typically effective for 6-12 months.

Alpha agonists

Class Summary

The tone of the musculature at the bladder neck is mitigated by alpha-adrenergic stimulation. The role of alpha agonists is to increase tone at the bladder neck, initiating a state of urinary retention, in an effort to decrease incontinence. However, these therapies are often not very effective.

Pseudoephedrine (Sudafed)

Stimulates vasoconstriction by directly activating alpha-adrenergic receptors of the respiratory mucosa. Induces bronchial relaxation and increases heart rate and contractility by stimulating beta-adrenergic receptors.

BPH, Alpha Blockers

Class Summary

These agents may decrease outlet resistance and reduce leak point pressures in patients with neurogenic bladder.

Tamsulosin (Flomax)

Tamsulosin is a selective alpha1-antagonist for the treatment of BPH. It has been used off-label on a study basis in an attempt to decrease outlet resistance and reduce leak point pressures in patients with neurogenic bladder.

Tricyclic antidepressants

Class Summary

These medications work by directly inhibiting bladder contractions through a mechanism unrelated to anticholinergic effects. They act to decrease bladder spasms and increase storage capacity.

Imipramine (Tofranil)

Facilitates urine storage by decreasing bladder contractility and increasing outlet resistance. Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine [5-HT]) at presynaptic neurons.

Antibiotics

Class Summary

These agents are used when indicated to treat acute infections. In patients with vesicoureteral reflux, they are often used as prophylaxis to prevent UTIs, which can potentially lead to pyelonephritis and renal damage.

Of the many antibiotics, 4 agents commonly used in the pediatric population are discussed below.

Trimethoprim and sulfamethoxazole (Bactrim, Septra)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity includes common urinary tract pathogens except Pseudomonas aeruginosa.

Amoxicillin (Trimox, Amoxil)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Nitrofurantoin (Furadantin, Macrodantin)

Synthetic nitrofuran that interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.

Antibiotic, Quinolone

Class Summary

UTIs are common in myelodysplasia and may require antibiotic treatment.

Ciprofloxacin (Cipro, Cipro XR, ProQuin XR)

Ciprofloxacin is a fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Ciprofloxacin has no activity against anaerobes. Continue treatment for at least 2 days (7-14 d typical) after signs and symptoms have disappeared.