Myelomeningocele and Associated Anomalies

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Chapter 117 Myelomeningocele and Associated Anomalies

Myelomeningocele, or spina bifida aperta, is defined as a dorsally protruding open spinal cord defect that usually is associated with spinal nerve paralysis and anomalies throughout the spinal axis. The goal of this chapter is to discuss and provide a description of the current management of myelomeningocele and its common associated anomalies in general, with special emphasis on associated spinal anomalies.

History and Epidemiology

Many epidemiologic studies have combined myelomeningocele with other defects such as anencephaly under the term neural tube defect (NTD). This grouping makes sense embryologically, because both myelomeningocele and anencephaly are open lesions that arise as a result of failure of primary neurulation and are separated in time by only one embryonic stage (2 days).

When describing NTD at birth, the term incidence is more clinically descriptive than is the term prevalence, because many affected fetuses abort spontaneously. NTDs exhibit wide geographic, ethnic, and gender variation. In the United States, NTD rates have declined from 1.3 per 1000 births in 1970 to 0.6 per 1000 births in 1989.¹ Worldwide, numbers range from 1 to 6 per 1000 births.² Superimposed on a general worldwide decrease in the incidence at birth of myelomeningocele, a number of influences cause both a reduction in prevalence at birth and an increased prevalence in the general population. Reduction of myelomeningocele at birth may result from maternal supplementation with folates and a higher rate of pregnancy termination due to availability of maternal serum α-fetoprotein testing and refined resolution of ultrasound for in utero fetal examination.

Recent improvements in neonatal and postoperative care have resulted in increased survival rates and, therefore, an increased prevalence in the general population. Zachary ³ believed that all affected infants should be operated on, even though many survivors inevitably will suffer from multiple handicaps. Worldwide, there are several variables considered and degrees of selection for candidacy for myelomeningocele treatment. The predominant factors are the level of the myelomeningocele and associated paralysis, the severity of associated hydrocephalus, and the presence of gross deformities. The overwhelming majority of untreated infants with myelomeningocele will die early in life.⁴

The evolution of myelomeningocele treatment over the last few decades also has led to a tremendous change in quality of life in affected patients. McLone ⁵ estimated that more than 75% of surviving infants with myelomeningocele will have normal intelligence; however, the frequency of learning disabilities is likely to be high. More than 80% will be ambulators by school age, while more than 90% will have bladder and bowel control.

Embryogenesis and Pathophysiology

During the last 100 years, various hypotheses have been proposed concerning the embryogenesis of myelomeningocele. Multiple experimental models and autopsy specimens were studied thoroughly. Myelomeningocele was produced in animal models genetically (e.g., curly tail mouse)⁶ or induced by medical or environmental factors such as vitamin A,⁷ valproic acid,⁸ salicylates,⁹ insulin,¹⁰ and hyperglycemic¹¹ and hyperthermic¹² conditions.

Current theories regarding the embryogenesis of dysraphic spinal lesions in general, and of myelomeningocele in particular, invoke a primary disorder of early neural tube development. This early defect of embryogenesis occurs in the fourth week of gestation. In normal embryos, the CNS originates from the neural tube, which is the thickening of the dorsal ectoderm. By the gradual elevation of the lateral margins of the neural tube, which are termed neural folds, the neural groove is formed. The neural folds meet in the midline and then form the neural tube. This process begins at the mesencephalic level and proceeds rostrally and caudally, with latest tube formation in the caudal spine at the caudal level.

Four different theories have been described: simple nonclosure, overgrowth and nonclosure, reopening (overdistention), and primary mesodermal insufficiency.⁷ Since its introduction, the nonclosure theory has gained almost universal acceptance because of its consistency with observations of early human embryos in which NTDs have been studied during or shortly after neural tube closure. Additional support has been provided by animal models of dysraphism, virtually all of which displayed a primary defect of neural tube closure.¹³

Myelomeningocele includes other consistent anomalies through the CNS axis, including Chiari II malformation and hydrocephalus. After studying the initial developmental defects of the Chiari II malformation using a genetically mutated NTD mouse model, McLone and Knepper ¹⁴ proposed a unified theory that describes and emphasizes the developmental sequence of associated anomalies. This pathophysiologic sequence starts with cerebrospinal fluid (CSF) leakage from the unclosed spinal defect. As a result, the usual distention and expansion of the developing ventricular system fails. The lack of distention of rhombencephalic vesicles alters the inductive effect of pressure on the surrounding mesenchyme and endochondral bone formation and results in small posterior fossa. Consequently, the development of the cerebellum and brainstem with a small posterior fossa leads to upward herniation and a dysplastic tentorium. Downward herniation results in a large foramen magnum and cerebellar vermis and brainstem displacement into the cervical segments (Chiari II malformation). Hydrocephalus is secondary to maldevelopment of the CSF pathways in the posterior fossa.

Most myelomeningoceles (85%) occur in the distal thoracic to lumbosacral spine. About 10% are detected in the higher thoracic area, and an additional 5% in the cervical area.¹⁵ Typically, a neural placode (plaque), which is unfolded neural tissue, appears at the center with a pia mater on the ventral surface. The ventral and dorsal nerve roots arise from the central surface of the placode, with the dorsal roots originating more laterally. Rostrally, the placode is continuous with the normal spinal cord within the spinal canal. At the periphery of the defect, the placode is circumscribed by arachnoid membrane that fuses with the free margins of the skin, fascia, and dura mater (Fig. 117-1). At involved levels, pedicles of vertebrae are displaced laterally, creating a widened spinal canal diameter. Vertebral bodies may be normal or wedge-shaped in the anteroposterior diameter, resulting in a kyphotic deformity.¹⁶

FIGURE 117-1 Preoperative photograph of a typical myelomeningocele.

Etiology

The etiology of myelomeningocele is multifactorial and heterogeneous. Experimental teratology has shown that several agents can increase occurrence rates: alcohol, carbamazepine,¹⁷ valproic acid,¹⁸ salicylates,⁹ insulin,¹⁰ clomiphene, influenza virus,¹⁹ and chemotherapeutic agents have all been incriminated. Population studies, however, have provided strikingly little evidence to suggest the role of a single teratogen as the sole cause of a significant number of myelomeningoceles.²⁰ Maternal age and birth order also may contribute to the risk of NTDs. Most studies show an excess of first-born children in the population of NTDs.²¹ In addition, most mothers of affected children are younger than 20 years of age or older than 35.²²

Although rarely clustered in families, a mendelian pattern of inheritance is evident. The recurrence risk for siblings of an affected individual is 2% to 5%, representing a 25- to 50-fold increase in recurrence risk compared with that of the general population.²³ A multicenter NTD genetic study reviewed the identification of genes predisposing to NTD through linkage analysis and candidate gene analysis along with characteristics of a large nationally ascertained cohort of families. Results from specific assessments of p53, PAX3, and MTHFR failed to suggest that these genes play a major role in NTD development in these families.²⁴ A frequent association was found between trisomy 13 and 18 and myelomeningocele in the fetus before 24 weeks (as high as 14%) but was rare in full-term infants, suggesting fetal demise.²⁵

Dietary factors related to NTDs were investigated extensively after several studies showed a progressive increase in the prevalence rate of NTDs in lower socioeconomic classes. Zinc deficiency has been considered because of a known increased risk of congenital defects in the offspring of animals fed a zinc-deficient diet,²⁶ but human studies have been inconclusive so far.²⁰

Folic acid antagonists, such as aminopterin, were shown to cause NTDs in animal studies, and since the publication of these studies, the effect of folic acid on prevention of myelomeningocele has been studied. In one study, serum and red blood cell levels of folate were decreased in mothers of children with myelomeningocele compared with controls.²⁷ Folic acid and multivitamin supplementation to high-risk mothers has been demonstrated to reduce the prevalence at birth of myelomeningocele in some populations.^27,²⁸ However, adherents to the folic acid prevention philosophy acknowledge that they cannot provide a reasonable mechanism of action.¹⁸

Repair of Myelomeningocele

Evaluation of the Newborn

Prenatal diagnosis and counseling have a significant effect on the preparation and decision-making process in cases of myelomeningocele.²⁹ Prenatal diagnosis of myelomeningocele involves the combined use of maternal serum α-fetoprotein screening and fetal ultrasonography.³⁰ Advances in ultrasound imaging have led to an increased rate of identification of myelomeningocele before birth. On detection, obstetricians usually refer the mother and family to a multidisciplinary team that includes a pediatric neurosurgeon, neonatologist, social worker, and spina bifida team coordinator. This referral facilitates postnatal treatment, including surgery, to be planned in a timely fashion, and informs and educates the family about the nature of myelomeningocele and its associated anomalies.¹⁵

Early closure of the spinal defect remains an important part of the modern management of children born with myelomeningocele. The rationale for early closure includes the prevention of ascending infection; preservation of motor, sensory, and intellectual function; establishment of a suitable environment for continued development of neural tissue; and cosmetic reconstruction.³¹ Most pediatric neurosurgeons agree that closure of the open myelomeningocele within the first 24 to 48 hours after birth decreases morbidity and mortality rates. Initiating surgery after 72 hours carries a significant risk of meningitis and ventriculitis,³² a decrease of motor function, and an increase in neurologic deficits.¹⁵

Postnatally, the myelomeningocele defect should be covered with a sterile dressing (wet or nonadherent dressing) before the infant is transferred to the neonatal intensive care unit. The newborn is kept in a prone or lateral recumbent position to protect the neural tissue by avoiding pressure on the placode. A thorough examination of the neonate should be conducted to assess the degree of neurologic deficit, the functional level, and associated concerns such as hydrocephalus and cardiopulmonary, genitourinary, and gastrointestinal conditions that could interfere with surgery of the myelomeningocele. Early urologic consultation is obtained with intermittent catheterization until adequate bladder function is ascertained.

A segmental motor examination should be obtained for future comparison. Observation of spontaneous hip flexion (L1-3), knee extension (L2-4), knee flexion (L5-S1), foot dorsiflexion (L4-5), and foot plantar flexion (S1-2) should be noted. If painful stimulus is required to elicit movement, it should be applied in a sensory dermatome well above those related to the lesion. Painful stimuli applied below the level of the lesion may elicit stereotypical reflex movements, which may be falsely interpreted as a functional motor segment. Gross asymmetry between the two lower extremities may indicate a more proximal lesion in the spinal cord (e.g., diastematomyelia, hemimyelocele).

More than 90% of neonates with myelomeningocele have some form of neurogenic bladder. Dribbling of urine as the neonate cries or moves is a strong indicator of future urinary incontinence, whereas periodic micturition with a good stream suggests a possibility of partial incontinence.³³ These infants also should be carefully inspected for characteristic external features that point to severe chromosomal abnormalities. Examination of the placode includes noting its shape and circumference, skin integrity, and extent of the cutaneous and epithelialized layers. The spinal column is examined for early congenital scoliosis, kyphosis, and palpable prominent laminae at the lateral margin of the lesion.