eMedicine Specialties > Pediatrics: Surgery > Urology

Myelodysplasia and Neurogenic Bladder Dysfunction

Author: Terry F Favazza, MD, Consulting Staff, Urologic Associates of Southern Arizona
Coauthor(s): Harry P Koo, MD, Chairman of Urology Division and Director of Pediatric Urology, Virginia Commonwealth University; Professor of Surgery, VCU School of Medicine, Medical College of Virginia; Director of Urology, Children's Hospital of Richmond
Contributor Information and Disclosures

Updated: Mar 27, 2008

Introduction

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 and treatment options and describes 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 mcg/d 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 85% of children with a myelomeningocele. 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 (approximately 5%) of patients with myelomeningoceles do not have a neurogenic bladder, but this is an 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. 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 2 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 widely vary, 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.

Frequency

United States

Reported prevalence of spinal dysraphism is 1 case per 1000 live births in the United States.¹ 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. 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

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

Mortality/Morbidity

The meningocele sac is often nothing more than a very thin transparent tissue that may be open and leaking CSF. This is a potential source of 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 rates in patients with myelodysplasia are significant. Myelodysplasia can contribute to voiding dysfunction, urinary tract infections (UTIs), vesicoureteral reflux, 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, requiring dialysis or transplantation.

• UTIs are common in infants with myelodysplasia, and patients must be promptly treated when UTIs are recognized. Recurrent infections, especially associated with poorly compliant bladder and vesicoureteral reflux, can lead to pyelonephritis, renal scarring, and an eventual loss of renal function. In the absence of reflux, patients with infections are usually treated symptomatically, but in children who experience recurrent infections, prophylactic treatment can be instituted.
• Vesicoureteral reflux occurs in 3-5% of infants with myelodysplasia and is usually associated with detrusor hyperreflexia or dyssynergia. If the neurogenic bladder remains untreated, incidence of vesicoureteral reflux increases with time until, by age 5 years, 30-40% of children are affected. Treatment of reflux 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, intermittent catheterization (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 (although rarely), and dialysis or transplantation may be needed.

Race

Studies have not shown a significant difference between races in the prevalence of myelodysplasia. However, a study from California demonstrated a slightly higher prevalence in children born to Hispanic mothers.² White mothers were the second most likely to have children with myelodysplasia, followed by black and Asian mothers.

Sex

Myelodysplasia is more common in females than in males.

Age

• Antenatal detection of myelodysplasia can be made using prenatal ultrasonography. If myelodysplasia is prenatally detected, 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 a 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.

Clinical

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

Physical

• 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 distension. In patients who require ventriculoperitoneal (VP) shunting, communicating hydroceles and hernias need to 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, which is discussed in 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.

Causes

The exact cause of dysraphism is unknown, but many factors appear to be involved. Genetic, environmental, and nutritional factors have been implicated, although 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%. Prevalence of myelodysplasia is increased in children born to mothers older than 30 years. Currently, no genetic markers have been linked to the presence of myelodysplasia.
• 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. Based on these data, the current RDA of 400 mcg/d 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.

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