Neural Tube Defects

Neural tube defects (NTDs) are a group of birth defects which are associated with a defective closure of the neural tube and the subsequent development of the central nervous system (brain and spinal cord). It is one of the most common birth defects occurring in approximately 0.7-1.0 per 1000 live birth each year (1,2). There are three types of NTDs: anencephaly, encephalocele, and spina bifida. Spina bifida, the most common NTD, means "split spine" in Latin and is a result of failure of the neural tube to close during the 3rd-5th week of pregnancy. The terminology can be confusing since multiple terms have been used for various conditions depending on the extent of the involvement of the spinal cord and surrounding structures.

Spinal dysraphism and spina bifida apply to a heterogeneous group which has defects of closure affecting the spinal canal (which may encompass the meninges and spinal cord itself in addition to bony vertebral elements). Myelodysplasia refers to defects of spinal cord development, which commonly occurs with spina bifida; however not necessarily associated with failure of fusion of the arches of the vertebral spine, so this could include entities such as syringomyelia and diastematomyelia. Spina bifida occulta is the simple failure of fusion of the spinal arches (i.e., bony involvement only), such that the neural elements are covered by skin and do not protrude above the level of the back. Occult spinal dysraphism means that spina bifida occulta is present with overlying cutaneous markers such as dimple, fistula, hair patch, and hemangioma. These markers may indicate the presence of cord tethering with a lipoma or a dermoid cyst. Spina bifida cystica is the commonest type of NTD which includes meningocele, meningomyelocele/myelomeningocele, lipomyelomeningocele. A meningocele is a lesion which does not involve neural elements in the cystic outpouching of the meninges. Meningomyelocele or myelomeningocele means that dysplastic neural elements protrude through the unfused vertebral arches. It can be completely covered with meninges and skin (closed meningomyelocele) or there may be a connection of spinal fluid to outside (open meningomyelocele). Lipomeningocele and lipomyelomeningocele are closed meningomyelocele with overgrowth of fatty tissue involving the meninges alone or including the spinal cord. The term spina bifida is ambiguous in that it is often used to describe conditions from spina bifida occulta to spina bifida with myelomeningocele.

The manifestations of the spina bifida depend on the level of the spinal cord involvement at which neural tube closure was incomplete. The lesion is located in lumbosacral area in more than 80% of the cases (3).

Children with the less common thoracic lesions, have flaccid paralysis of lower extremities with variable weakness in abdominal and trunk musculature. These defects are frequently associated with serious complications (e.g., respiratory compromise). Children with high lumbar lesions (L1, L2) have flaccid paralysis of knees and ankles and may walk with extensive braces and crutches. Children with midlumbar lesions (L3) have paralyzed ankles and toes. These children can accomplish independent ambulation with braces. Children with low lumbar lesions (L4, L5) often have weak ankle and toe mobility. They are particularly prone to ankle or foot deformities and often need orthosis for independent ambulation.

Bladder and bowel problems are present in more than 90% of children with meningomyelocele regardless of the level of lesion (1). Some children may have problems with bladder emptying, while others may have problems with storing the urine adequately. Despite the type of neurogenic bladder, it is crucial to prevent urinary tract infections and protect the upper urinary tract since renal failure is one of the important causes of death among these children. Bowel continence requires normal external sphincter control, internal sphincter reflex relaxation, rectal sensation and colonic motility. Lack of sensation and inability to control external sphincters makes these children unable to sense or control stool passage. Bowel management programs with regularly scheduled toileting, use of stool softeners, and dietary measures (i.e., additional fiber) are important to avoid constipation and soiling.

Spina bifida is often not only an isolated birth defect of the spinal cord and spine, but there commonly are associated congenital malformations of the brain. Hydrocephalus is a major complication of meningomyelocele and is present at birth in 85-95% of cases as shown by ultrasonography (3,4). These children with hydrocephalus require ventriculoperitoneal shunt (VP shunt) placement. Shunt malfunction and infection are frequent complications and most children eventually require shunt revision (30-40% within one year of insertion of the shunt). Lethargy, vomiting, irritability, bulging and tense fontanelle, and headache, are common symptoms of shunt malfunction. Seizures also occur in up to 17% of the children with meningomyelocele and almost always occur in those with hydrocephalus (5).

Arnold-Chiari II malformation (the cause of the hydrocephalus) is present in the majority of children with meningomyelocele. The cerebellum and medulla oblongata are shifted caudally, so this resultant packing into the cervical spinal canal results in deformation. The symptoms are due to progressive hydrocephalus (if untreated) and dysfunction of the lower cranial nerves, respiration and swallowing. Hydrocephalus occurs in most children secondary to aqueductal stenosis or obstruction to CSF flow around the medulla.

Any clinical changes in children with meningomyelocele should prompt a search for an underlying cause. By far, the most common cause of deterioration is shunt malfunction. Another important cause is tethering of the spinal cord. Up to one third of children with myelodysplasia may experience spinal cord tethering. A tethered spinal cord results from traction on the conus medullaris and cauda equina, which causes spinal cord stretching and ischemia with subsequent loss of neurological function. Symptoms of a tethered spinal cord include spasticity, weakness, decreased sensation in the lower extremities, changes in urinary and bowel functions, or back pain, progressive scoliosis and foot deformity. Some children with occult spinal dysraphism (i.e., no overlying meningomyelocele) are asymptomatic and truly have an occult spinal cord condition. An MRI scan will identify the spinal abnormality. Surgery is indicated in symptomatic patients. Prophylactic intervention among asymptomatic children can prevent the long-term disabilities associated with this condition.

Mastery of bowel and bladder continence is crucial to optimal functioning and is of the major importance for social acceptance. The voiding program may include medications, intermittent catheterization, and possibly operative reconstruction. Clean intermittent catheterization is the most commonly used method to help urinary continence. It is used to remove residual urine, improve urinary drainage, and provide decompression. The goal is to have this task accomplished by early school age. A child's physical abilities and psychological readiness for toileting should be assessed and continued assistance may be necessary for some children.

Children with physical disabilities are often described by their disabilities, and not by their strengths or abilities, which are also important. Children with spina bifida are often automatically placed in regular classes or classes for children with orthopedic problems. Although this is frequently the best placement, there are children whose orthopedic problems are secondary and their learning disability associated with spina bifida may be the major disability. Children with spina bifida and hydrocephalus may have problems with motor skills, attention, memory and organization. These issues should be understood and addressed in the Individualized Education Program (IEP).

Latex allergy has been common among children with spina bifida (about 20-70%) (6). Although the cause of latex allergy in children with spina bifida is not known, it may be due to the early, intense, constant exposure to rubber products among these children. Latex comes from the sap of the rubber tree Hevea brasiliensis. After the commercial purification process there are small amount of residual proteins that could cause allergy symptoms ranging from mild skin rashes or sneezing to hives, respiratory distress and anaphylactic shock. 

Many products contain rubber components of which we are unaware and environmental exposure to rubber products in both the community and hospital is widespread (e.g., rubber bands, erasers, gym mats, certain paints and glues, elastic waist or leg bands in clothing and disposable diapers). There are some food items (e.g., bananas, avocado, chestnuts) which can also cause cross-reactions. Prevention is the best approach. This allergic condition should be documented on medical and school records, communication devices such as medical alert bracelet should be provided as well as auto-injectable epinephrine as a part of the emergency plan for these children. In fact, it is commonly recommended that all children with spina bifida and/or myelodysplasia be kept latex free even if allergy has not yet been demonstrated.

The initial treatment for spina bifida is early surgical closure of the defect. Because of the multisystem involvement of this condition as stated above, management of this condition requires a comprehensive, multidisciplinary team approach. This team may include pediatricians, nurses, specialists (neurologists, neurosurgeons, urologists, orthopedists, developmental-behavioral pediatricians), physical therapists, occupational therapists, social workers, and special education teachers.

Alpha-fetoprotein (AFP) is elevated in maternal serum (MSAFP) and amniotic fluid (AFAFP) in open NTDs such as encephalocele, meningomyelocele and anencephaly. It is also increased in other conditions such as abdominal wall defects (gastroschisis and omphalocele). AFP becomes measurable in maternal serum at the end of first trimester. Maternal blood sample measurements are collected between 16-18 weeks of gestation to provide enough time for more definitive testing as necessary and to allow sufficient time for decision making regarding continuation or termination of an affected pregnancy. The MSAFP level is affected by gestational age and the number of fetuses. Elevated AFP level in amniotic fluid is more definitive than MSAFP, identifying 90-95% of affected fetuses with open NTDs. Acetylcholinesterase assay is more specific for neural tissue with a 99% accuracy rate. Ultrasonography also has been increasingly accurate in prenatal diagnosis of fetal anomalies.

Folic acid is a synthetic compound used in dietary supplements and fortified foods. The term folate includes all compounds that have the vitamin properties of folic acid (folic acid and naturally occurring compounds in food). The average diet in the United States contains 200 microgram of naturally occurring folate, which is less bioavailable than folic acid. Studies have demonstrated that 50% or more NTDs can be prevented if women consume a folic acid supplement before and during the early weeks of pregnancy. The American Academy of Pediatrics endorses the US Public Health Service recommendation that all women capable of becoming of pregnant consume 400 microgram of folic acid to prevent NTDs.

Studies have shown improved long term outcome regarding ambulation, urinary continence, and social continence of stool. One of the studies also showed that about 60% of children with spina bifida attended regular school programs. These outcomes depend on the level of lesion and the severity of complications. 

Department of Pediatrics, University of Hawaii John A. Burns School of Medicine.

Mari Uehara, MD 

October 2002