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. Zachary3 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. McLone5 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 Knepper14 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

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.

Surgical Repair

After identification of the neural placode and cerebrospinal fluid flowing from the central canal, dissection begins and is continued in a circumferential fashion, dividing the placode from the epithelial layer. This will allow the surgeon to see the pia-arachnoid attached at the periphery of the neural placode. It is essential to understand that, developmentally, the lateral edges of the ventral surface of the placode are the alar plate or the dorsal root entry zones. Dorsal nerve roots (sensory) are observed in this region. The medial portion of the ventral surface of the placode is the basal plate, which contains the ventral nerve roots (motor). Thus, the pia-arachnoid meets the neural placode at the lateral margin of the ventral surface of the placode.

The neural tissue is then gently freed from any ventral arachnoid adhesions, using microdissection techniques. When this has been completed, the flat neural placode should be free throughout its circumference and ready for dorsal reapproximation. Beginning rostrally, the pia-arachnoid neural junction of each lateral edge should be brought together in the dorsal midline. Care should be taken to engage only the pia with each pass of the suture, avoiding injury to the sensory roots.

The dura mater is located just beneath the skin edge laterally. Its lateral attachment is incised and the epidural space identified (often marked by the presence of epidural fat). The dura mater should be freed rostrally and caudally to the apices of the defect on each side so that the free edges come together in the midline dorsally. The dura mater is closed in a watertight fashion. The closure should be patulous to prevent spinal cord ischemia and tethering. Occasionally, a dural graft may be required. Intradural hemostasis should be meticulous to minimize late fibrosis and scarring. With all these surgical procedures, latex reactions should be considered.34

Reapproximation of the paraspinous muscles over the repair may require some lateral dissection for mobilization. In the presence of a kyphos, the paraspinous muscles can act as spine flexors because of their lateral position, which, owing to the deformity, is ventral to the neural axis of the spine. The paraspinous muscles may then be repositioned in the normal anatomic location: dorsal and paramedian. The dorsal fascia can now be reapproximated. A continuous suture with intermittent, interrupted sutures can be used for this layer to further reinforce the watertight dural closure. It is important to note that adequate mobilization of the paraspinous muscles is crucial to prevent constriction of the underlying neural elements.15

Closure of the skin in the midline can be facilitated by a generous blunt subcutaneous dissection for mobilization. The proper plane for this blunt dissection is just superficial to the dorsal fascia. Continuous monofilament suture is used for skin closure, which further reinforces the layer by watertight closure. Occasionally, the defect is so large that skin closure cannot be accomplished without undue tension. Consultation with a plastic surgeon may be obtained if adequate skin closure is difficult or even impossible. Several surgical techniques have been used in this situation, including local rotated skin flaps, tissue expansion,35 relaxation of the lateral incisions with a skin graft,36 and a Limberg-latissimus dorsi myocutaneous flap.37

A recent development in myelomeningocele closure involves the in utero closure of myelomeningocele defects. The rationale for fetal repair of myelomeningoceles and initial clinical outcomes have been discussed over the last few years. The development of techniques to close open neural tube malformations prior to birth has generated great interest and hope for fetal interventions and their outcomes. In most recent series of patients, intrauterine myelomeningocele repair appeared to decrease the incidence of hindbrain herniation and shunt-dependent hydrocephalus in infants with myelomeningocele, but increased the incidence of premature delivery. Long-term improvement of neurologic outcome and prevention of hindbrain herniation and hydrocephalus has yet to be proven.3841

Associated Anomalies

A multitude of associated anomalies are common in infants with myelomeningocele. CNS anomalies are more common than other systemic anomalies. Microgyria, polygyria, enlargement of the massa intermedia, agenesis or dysgenesis of the corpus callosum, and cerebellar dysgenesis, along with Chiari II malformation, are common findings that can be encountered on MRI. The midbrain, especially the tectal area, can be beaked, and the aqueduct of Sylvius can be anomalous. The pons and medulla oblongata are bowed dorsally and often extend into the rostral cervical spinal canal along with the cerebellar vermis and tonsils.15

In a series of autopsies on infants with the myelomeningocele and Chiari malformations, cerebral and cerebellar cortical malformations were found in 92% and 72% of cases, respectively. Heterotopias (i.e., displaced, well-formed gyri and folia), heterotaxias (i.e., disordered combinations of mature neurons and germinal cells), immature germinal cell collections, microgyria, and polymicrogyria were observed. Ventricular system anomalies were present in 92% of cases in the same series, including atresia, stenosis, and forking of the cerebral aqueduct. Atresia of the third ventricle and stenosis of the fourth ventricle occurred rarely. Other uncommon findings included septum pellucidum cysts and agenesis of the olfactory tracts and bulbs.42

Systemic anomalies also occur and should be considered independently when assessing infants with myelomeningocele and Chiari malformations for surgical intervention. Associated systemic anomalies appear in the gastrointestinal, pulmonary, and cardiovascular systems and in the craniofacial structures.43 The most common anomalies in the genitourinary system include hydroureter and hydronephrosis, which usually occur after long-standing neurogenic bladder. Gastrointestinal anomalies include inguinal hernia, Meckel diverticulum, malrotation, omphalocele, and imperforate anus. Cardiovascular anomalies include ventricular or atrial septal defects, patent ductus arteriosus, and coarctation of the aorta.44

Hydrocephalus

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