NEURAL TUBE DEFECTS PATHOLOGY

Pathology
Spina bifida cystica
The 2 major types of defects seen with spina bifida cystica are myelomeningoceles and meningoceles. Cervical and thoracic regions are the least common sites, and lumbar and lumbosacral regions are the most common sites for these lesions.

Myelomeningocele is a condition in which the spinal cord and nerve roots herniate into a sac comprising the meninges. This sac protrudes through the bone and musculocutaneous defect. The spinal cord often ends in this sac in which it is splayed open, exposing the central canal. The splayed open neural structure is called the neural placode. This type of NTD is the subject of most of this article. Certain neurologic anomalies, such as hydrocephalus and Chiari II malformation (discussed later in this article), accompany myelomeningocele. In addition, myelomeningoceles have a higher incidence of associated intestinal, cardiac, and esophageal malformations, as well as renal and urogenital anomalies. Most neonates with myelomeningocele have orthopedic anomalies of their lower extremities and urogenital anomalies due to involvement of the sacral nerve roots.

A meningocele is simply herniation of the meninges through the bony defect (spina bifida). The spinal cord and nerve roots do not herniate into this dorsal dural sac. These lesions are important to differentiate from a myelomeningocele because their treatment and prognosis are so different from myelomeningocele. Neonates with a meningocele usually have normal examination findings and a covered (closed) dural sac. Neonates with meningocele do not have associated neurologic malformations such as hydrocephalus or Chiari II.

A subtype of spina bifida is called lipomeningocele, or lipomyelomeningocele, which is a common form of NTD treated by pediatric neurosurgeons. These lesions have a lipomatous mass that herniates through the bony defect and attaches to the spinal cord, tethering the cord and often the associated nerve roots. The lipomyelomeningocele can envelop both dorsal and ventral nerve roots, only the dorsal nerve roots, or simply the filum terminale and conus medullaris. These lesions do not have associated hydrocephalus but have a more guarded prognosis than simple meningoceles. The surgical correction of these lesions is more complex, and the retethering rate in which an additional surgery is required is as high as 20% in some series.

In a third rare type of spina bifida cystica called myelocystocele, the spinal cord has a large terminal cystic dilatation resulting from hydromyelia. The posterior wall of the spinal cord often is attached to the skin (ectoderm) and is undifferentiated, thus giving rise to a large terminal skin-covered sac. The vast majority of the lesions are dorsal, although a small minority (approximately 0.5%) are ventral in location. The most common ventral variant is an anterior sacral meningocele, which most often is discovered in females as a pelvic mass.

Spina bifida occulta
In this group of NTDs, the meninges do not herniate through the bony defect. This lesion is covered by skin (ie, closed), therefore rendering the underlying neurologic involvement occult or hidden. These patients do not have associated hydrocephalus or Chiari II malformations. Often, a skin lesion such as a hairy patch, dermal sinus tract, dimple, hemangioma, or lipoma points to the underlying spina bifida and neurologic abnormality present in the thoracic, lumbar, or sacral region. Presence of these cutaneous stigmata above the gluteal fold signifies the presence of an occult spinal lesion. Dimples below the gluteal fold signify a benign, nonneurologic finding such as a pilonidal sinus. This is an important point for differentiating the lesions that have neurologic involvement from those that do not.

An experienced pediatrician or surgeon should examine any neonate with cutaneous stigmata on the back around the gluteus. A good rule of thumb is that a lesion (eg, pit, tract) below the gluteal crease is often a pilonidal sinus and needs no further evaluation. Those tracts, pits, or lesions above the gluteal fold should be evaluated with further study.

Lesions that are questionable can be scanned with ultrasound in a neonate or with MRI in an older child. The ultrasound or MRI delineates the presence or absence of a tethered cord or other spinal anomaly. Plain radiology can reveal a panoply of anomalies, such as fused vertebrae, midline defects, bony spurs, or abnormal laminae. An MRI often is useful in evaluating for a split cord malformation (ie, diastematomyelia), in which a bony spur splits the spinal cord, or a duplication of the spinal cord and nerve roots (diplomyelia). More commonly, the neurosurgeon is searching for tethering of the spinal cord by a sinus tract or thickened filum that can cause traction on the spinal cord with subsequent neurologic deficits as the child grows.

A growing body of evidence indicates that the surgical repair of these lesions is more effectively performed in a prophylactic fashion. Once the patient experiences a significant neurologic deficit such as a neurogenic bladder or leg weakness from these occult spinal lesions, the surgical remedy may not return the patient to previous neurologic status.

Signs and symptoms of occult spinal disorders in children include the following:
• Radiologic signs
o Lamina defects
o Hemivertebrae
o Scoliosis
o Widening of interpedicular distance
o Butterfly vertebrae

• Cutaneous stigmata
o Capillary hemangioma
o Caudal appendage
o Dermal sinus
o Hypertrichosis

• Orthopedic findings
o Extremity asymmetry
o Foot deformities

• Neurological problems
o Weakness of leg or legs
o Leg atrophy or asymmetry
o Loss of sensation, painless sores
o Hyperreflexia
o Unusual back pain
o Abnormal gait
o Radiculopathy

• Urologic problems
o Neurogenic bladder
o Incontinence

Cranium bifida
Several types of midline skull defects are classified under this term, ranging from simple, with minimal clinical significance, to serious life-threatening conditions. The most benign type of cranium bifidum occultum is the persistent parietal foramina or persistent wide fontanelle. The parietal foramina can be transmitted as an autosomal dominant trait via a gene located on the short arm of chromosome 11. The condition is sometimes called "Caitlin marks," after the family for which it was described. Both parietal foramina and a persistent anterior fontanelle are generally asymptomatic and a pediatric neurosurgeon may be asked to evaluate the child for skull fracture, craniosynostosis, or some other reason related to these findings. The best management is observation over time, as these skull defects often close over time.

Cranium bifidum such as an encephalocele is much more serious. Encephaloceles are theorized to occur when the anterior neuropore fails to close during days 26-28 of gestation. Incidence of this anomaly is 10% of the incidence of spina bifida cystica. In the United States, approximately 80% of lesions are found on the dorsal surface of the skull, with most near the occipital bone. In contradistinction, most encephaloceles in Asia are ventral and involve the frontal bone. In the Philippines and other Pacific countries, incidence of anterior encephaloceles that present as hypertelorism, obstructed nares, anterior skull masses, and cleft palate, among other presentations, is high. In most lesions, the sac that has herniated through a midline skull defect is covered with epithelium.

A small number of encephaloceles are associated with syndromes such as Meckel-Gruber syndrome. This syndrome is characterized by an occipital encephalocele that is associated with holoprosencephaly, orofacial clefts, microphthalmia, polycystic kidneys, and cardiac anomalies. This condition is autosomal recessive and has been mapped to chromosome bands 17q21-q24. In the United States, only about 30% of occipital encephaloceles contain cerebral cortex. The rest contain cerebellar tissue, dysplastic tissue with little normal function, glial tissue, or are simple meningeal sacs filled with CSF (as in cranial meningocele).

An MRI is invaluable in planning a surgical approach. The surgeon needs to know the contents of the sac, which can be quite large. In addition, the surgeon needs to know the relationship of the major cerebral venous sinuses to the sac in order to plan a safe operative approach. Finally, the surgeon needs to know if the patient has hydrocephalus. Approximately 60% of these patients require placement of a ventricular peritoneal (VP) shunt after the removal of their encephalocele. Children whose encephaloceles contain large quantities of cerebral cortex often become microcephalic and display significant developmental and learning disabilities.

Anencephaly
Anencephaly is the most severe form of NTD. Rachischisis and craniorachischisis, often used as synonyms, refer to a severe deformity in which an extensive defect in the craniovertebral bone causes the brain to be exposed to amniotic fluid. Neonates with anencephaly rarely survive more than a few hours or days. Historically, these children have been the subject of myths, folklore, and superstitions, and have been referred to as monsters based on their unusual and frightening appearance. More recently, scientists have studied this malformation because it serves as a paradigm of the other dysraphic states.

The fetus has a partially destroyed brain, deformed forehead, and large ears and eyes with often relatively normal lower facial structures. Both genetic and environmental insults appear to be responsible for this outcome. The defect normally occurs after neural fold development at day 16 of gestation but before closure of the anterior neuropore at day 24-26 of gestation.

A variety of teratogens have been implicated, including radiation, folic acid deficiency, drugs, and infections. Regardless, 3 basic defects occur in the developing fetus. The first is the defect in notochord development, which results in failure of the cephalic folds to fuse in the midline and make a normal neural tube. The next defect is failure of the mesoderm to develop; mutual induction of all 3 germ layers in a temporally related sequence fails to occur. Therefore, the calvarium and vertebrae (mesoderm) fail to form correctly, exposing the brain to further insult. Finally, this skull and dural defect permits the brain to be exposed to amniotic fluid, thus destroying the developing forebrain neural cells.

Anencephaly is the most common major central nervous system (CNS) malformation in the Western world, and no neonates survive. It is seen 37 times more frequently in females than in males. The recurrence rate in families can be as high as 35%. The incidence is highest in Ireland, Scotland, Wales, Egypt, and New Zealand and lowest in Japan.