I. DEFINITIONS AND PATHOLOGY. The central nervous system (CNS) starts as a neural tube and folds into the brain and spinal cord by a complex mechanism during early embryologic development. Failure of normal closure results in neural tube defects, one of the most serious congenital malformations in newborns. The term refers to a group of disorders that is heterogeneous with respect to embryologic timing, involvement of specific nervous system elements, clinical presentation, and prognosis.

1. Primary neural tube defects constitute the majority of neural tube defects and can be viewed as due to primary failure of closure of the neural tube or disruption of an already closed neural tube between 18 and 25 days’ gestation. The resulting abnormality usually manifests in two anatomic lesions: an exposed (open or aperta) neural placode along the midline of the back caudally and rostrally and the Arnold-Chiari II (ACII) malformation (malformation of pons and medulla, with downward displacement of cerebellum, medulla, and fourth ventricle into the upper cervical region), with associated aqueductal stenosis and hydrocephalus.

a. Myelomeningocele is the most common primary neural tube defect. It involves a saccular outpouching of neural elements (neural placode), typically through a defect in the bone and the soft tissues of the posterior thoracic, sacral, or lumbar regions—the latter comprising 80% of lesions. Arachnoid is typically included in the sac (meningo), which contains
visible neural structures (myelo), and the skin is discontinuous over the sac. Hydrocephalus occurs in around two-thirds of these children; Chiari II malformation occurs in approximately 90%, although the link between hydrocephalus and the malformation has been significantly reevaluated in recent years, with therapeutic implications discussed in the following text. Various associated anomalies of the CNS are noted, most importantly, cerebral cortical dysplasia in up to 92% of cases.

b. Encephalocele. This defect of anterior neural tube closure is an outpouching of dura with or without brain, noted in the occipital region, in 80% of cases for North America and Europe, and less commonly in the frontal, parietal, or temporal regions. It may vary in size from a few millimeters to many centimeters.

c. Anencephaly. In the most severe form of this defect, the cranial vault and posterior occipital bone are defective, and derivatives of the neural tube are exposed, including both brain and bony tissue. The defect usually extends through the foramen magnum and involves the brainstem. It is not compatible with long-term survival. Rachischisis is a more severe form in which the spine is also involved due to nonfusion of the majority of the primary neural tube.

2. Secondary neural tube defects. Five percent of all neural tube defects result from abnormal development of the lower sacral or coccygeal segments during secondary neurulation. This leads to defects primarily in the lumbosacral spinal region. These heterogeneous lesions are rarely associated with hydrocephalus or the Chiari II malformation, and the skin is typically intact over the defect. Because the hindbrain abnormality of the Chiari II malformation is evident on prenatal scans, this radiographic finding is useful in distinguishing open from closed neural tube abnormalities.

a. Meningocele is a spinal fluid-filled sac causing an outpouching of skin and dura without involvement of the neural elements aside from a commonly associated dorsal band of neurovascular tissue adherent to the sac. Meningoceles may be associated with bone and contiguous soft tissue abnormalities.

b. Lipomeningocele is a lipomatous mass usually in the lumbar or sacral region, occasionally off the midline, typically covered with full-thickness skin. Adipose tissue frequently extends through the defect into the spine and dura and adheres extensively to a distorted spinal cord or nerve roots.

c. Filum lipoma, sacral agenesis/dysgenesis, diastematomyelia, myelocystocele, all may have varying degrees of bony involvement. Although rarely as extensive as with primary neural tube defects, neurologic manifestations may be present representing distortion or abnormal development of neural structures. These lesions may be inapparent on physical examination of the child, resulting in the use of the term occulta to describe them.

B. Etiologies. The exact cause of failed neural tube closure remains unknown, and proposed etiologies for both primary and secondary neural tube defects are heterogeneous. Factors implicated include folic acid deficiency; maternal ingestion of the anticonvulsants carbamazepine and valproic acid and
folic acid antagonists such as aminopterin and certain antimalarial drugs; maternal diabetes; and disruptive influences such as prenatal irradiation and maternal hyperthermia. A genetic component is supported by the fact that there is concordance for neural tube defect in monozygotic twins and an increased incidence with consanguinity and with a positive family history. Neural tube defects can occur with trisomies 13 and 18, triploidy, and Meckel syndrome (autosomal recessive syndrome of encephalocele, polydactyly, polycystic kidneys, cleft lip and palate), as well as other chromosome disorders. Although specific genes (particularly those in the folatehomocysteine pathway as well as in genes involved in planar cell polarity) have been implicated as risk factors, the genetics are likely complex and multifactorial (see Chapter 10).

C. Epidemiology and recurrence risk. The incidence of neural tube defects varies significantly with geography and ethnicity. In the United States, the overall frequency of neural tube defects is approximately 1 in 2,000 live births. The literature may underestimate the true prevalence because of the effects of terminating prenatally diagnosed pregnancies. A well-established increased incidence is known among individuals living in parts of Ireland and Wales and carries over to descendants of these individuals who live elsewhere in the world. This may be true also for other ethnic groups, including Sikh Indians and certain groups in Egypt. More than 95% of all neural tube defects occur to couples with no known family history. Primary neural tube defects carry an increased empiric recurrence risk of 2% to 3% for couples with one affected pregnancy, with a higher risk if more than one sibling is affected. Similarly, affected individuals have a 3% to 5% risk of having an offspring with a primary neural tube defect. Recurrence risk is strongly affected by the level of the lesion in the index case, with risks as high as 7.8% for lesions above T11. In 5% of cases, neural tube defects may be associated with uncommon disorders; some, such as Meckel syndrome, are inherited in an autosomal recessive manner, resulting in a 25% recurrence risk. Secondary neural tube defects are generally sporadic and carry no known increased recurrence risk. In counseling families for recurrence, however, it is critical to obtain a careful family history and history of drug exposure.

D. Prevention. Controlled, randomized clinical studies of prenatal multivitamin administration both for secondary prevention in mothers with prior affected offspring and for primary prevention in those without a prior history have shown a 50% to 70% reduced incidence of neural tube defects in women who take multivitamins for at least 3 months prior to conception and during the first month of pregnancy.¹ The Centers for Disease Control and Prevention recommends that women of childbearing age who are capable of becoming pregnant consume 0.4 mg of folic acid per day to reduce their risks of having a fetus affected with myelomeningocele or other neural tube defects. Higher doses are recommended for women with prior affected offspring. In addition, folate supplementation of enriched cereal-grain products has been mandated by the U.S. Food and Drug Administration (FDA); however, the level of folate intake from this source is not high enough to forgo additional supplementation in the large majority of women.

A. Prenatal diagnosis. The combination of maternal serum α-fetoprotein (AFP) determinations, prenatal ultrasonography, rapid-acquisition fetal magnetic resonance imaging (MRI) scans, and AFP and acetylcholinesterase determinations on amniotic fluid where indicated, greatly improves the ability to make a prenatal diagnosis and to distinguish from abdominal wall defects. Maternal serum AFP measurements of 2.5 multiples of the median (MoM) in the second trimester (16 to 18 weeks) have a sensitivity of 80% to 90% for myelomeningocele. The exact timing of this measurement is critical as AFP levels change throughout pregnancy. Karyotype may also be performed at the time of amniocentesis to detect associated chromosomal abnormalities. Ultrasonographic diagnosis through direct visualization of the spinal defect or through indirect signs related to Arnold-Chiari malformation has a sensitivity of >90%. The Chiari malformation is seen as a flattened cerebellum called a “banana sign” and a transient frontal bone anomaly called a “lemon sign.” Ultrasound can also demonstrate the level of termination of the normal cord and placode. Prenatal MRI may define the defect more accurately. Determining the prognosis based on prenatal ultrasonography remains difficult, except in obvious cases of encephalocele or anencephaly (see Chapter 1) but an appreciation of the level of disruption can be helpful in that higher spinal levels within the thoracolumbar range portend a correspondingly higher level of neurologic deficit. Some patients with higher thoracic or cervical lesions, however, have remarkable preservation of function; often, restitution of the spinal cord below the lesion is evident by MRI in these cases.

B. Postnatal diagnosis. Except for some secondary neural tube defects, most neural tube defects, especially meningomyelocele, are immediately obvious at birth. Occasionally, some saccular masses, usually in the low sacrum, including sacrococcygeal teratomas, can be mistaken for a neural tube defect. Rarely, anterior sacral meningoceles can occur that are not evident at birth.

A. History. Obtain a detailed family history. Ask about the occurrence of neural tube defects and other congenital anomalies or malformation syndromes. Note should be made of any of the risk factors described in the preceding text, including maternal medication use in the first trimester or maternal diabetes.

B. Physical examination. It is important to perform a thorough physical examination, including a neurologic examination. The following portions of the examination are likely to reveal abnormalities.

1. Back. Inspect the defect and note if it is leaking cerebrospinal fluid (CSF). Use a sterile nonlatex rubber glove when touching a leaking sac (in most circumstances, only the neurosurgeon needs to touch the back). Note the location, shape, and size of the defect and the thin “parchment-like” overlying skin, although it has little relation to the size of the sac. Often, the sac is deflated and has a wrinkled appearance. It is important to note the curvature of the spine and the presence of a
bony gibbus underlying the defect. For suspected closed lesions, document hemangioma, hairy patch, deep dimple, or sinus tract, if present; ultrasonography of the lower spine can show the level of the conus and presence of normal root movement in cases where this is in question.

2. Head. Record the head circumference and plot daily until stable postoperatively. At birth, some infants will have macrocephaly because of hydrocephalus, and still, more will develop hydrocephalus after closure of the defect on the back. Ultrasonography is useful to assess ventricular size. Assess the intracranial pressure (ICP) with the baby sitting upright by palpating the anterior fontanel and tilting the head and torso forward until the midportion of the anterior fontanel is flat. The fontanels may be quite large and the calvarial bones widely separated (see Chapter 54).

3. Eyes. Abnormalities in conjugate movement of the eyes are common and include esotropias, esophorias, and abducens paresis.

4. Neurologic examination. Observe the child’s spontaneous activity and response to sensory stimuli in all extremities. Predicting ambulation and muscle strength based on the “level” of the neurologic deficit can be misleading, and very often, the anal reflex, or “wink,” will be present at birth and absent postoperatively, owing to spinal shock and edema.

5. Lower extremities. Look for deformities (e.g., clubfeet) as well as muscle weakness and limited range of motion. Examine the thigh positions and skinfolds and perform the Ortolani and Barlow maneuvers for evidence of congenital dysplasia of the hips. With open lesions, this exam should be deferred until after the repair of the meningomyelocele. Dislocation of the hips can also be diagnosed by ultrasonography (see Chapter 58).

Repeated neurologic examinations at periodic intervals is more helpful in predicting functional outcome than a single newborn examination. Similarly, sensory examination of the newborn can be misleading because of the potential absence of a motor response to pinprick. Carefully examine deep tendon reflexes (see Table 57.1).

6. Bladder and kidneys. Palpate the abdomen for evidence of bladder distension or kidney enlargement. Observe the pattern of urination and check the infant’s response to the Credé maneuver to evaluate residual urine in the bladder.

C. General newborn assessment. Evaluate all newborns with neural tube defects for the presence of congenital heart disease (especially ventricular septal defect [VSD]), renal malformation, and structural defects of the airway, gastrointestinal tract, ribs, and hips. Although uncommon in primary neural tube defects, these can be encountered and should be considered before beginning surgical treatment or before discharge from the hospital. Other findings of associated chromosomal anomalies may be noted. In addition, plan an ophthalmologic examination and hearing evaluation during the hospitalization or following discharge.

IV. CONSULTATION. The care of an infant with a neural tube defect requires the coordinated efforts of a number of medical and surgical specialists as well as


specialists in nursing, physical therapy, and social service. Some centers have a neural tube defect team to help coordinate the following specialists.