Basics of Spina Bifida

1. Introduction

Spina bifida refers to a group of congenital deformities of the spine. Spina bifida is closely related to cranium bifidum, a congenital deformity of the skull. Both spina bifida and cranium bifidum result from failure of neural tube development and are referred to as neural tube defects (NTDs). NTDs represent the second most common type of congenital defect in the United States, only second to cardiac defects. The nervous system begins to develop early in embroygenesis. At the 3rd week of gestation, a mass of ectodermal cells comprising the neural plate envaginate to form the neural groove. The neural groove first closes along its length, followed by closure of the anterior neuropore by day 25 or 26 and of the posterior neuropore a few days after that. The failure of normal neural tube closure 25 to 28 days after conception results in NTDs.

2. Presentation

Spina bifida can take many forms. Commonly, spina bifida is classified as Spina bifida occulta, which is less severe, and spina bifida cystica, which is more severe. Spina bifida cystica can be further divided into meningocele and myelomeningocele. Cranium bifidum can be classified as anencephaly and encephalocele.

Spina bifida occulta is a very common congenital birth defectI which consists of a defect in only a few vertebrae while the spinal cord and meninges are unaffected. There is no opening of the back and thus the defect is said to be“hidden” hence the name “occulta”. However, on clinical exam one may find a tuft of hair or a dimple. This condition is usually asymptomatic, though it may present with more severe accompanying malformations, including syringomyelia (cystic cavitation of the spinal cord), diastematomyelia (midline sagittal clefting of the spinal cord), or a tethered cord (tip of the conus medullaris is prevented from ascending in the spinal cord). When spina bifida occulta occurs with associated malformations, it may be termed occult spinal dysraphism. Patients with occult spinal dysraphism commonly present with hemangioma, pit, lump or hairy patch on the lower back. In absence of other malformations, spina bifida occulta commonly remains undetected until x-rays are taken for unrelated reasons.

Meningocele occurs when the meninges herniate through a defect in the posterior vertebral arch. The herniated meninges protrude from the infant’s back and form a sac filled with cerebrospinal fluid (CSF). The neural tissue is generally unaffected, through meningocele may present with syringomyelia, diasemtomyelia, or a tethered chord, as in occult spinal dysraphism. Skin or a thin membrane can cover the protruding sac. If the covering is thick, complications are less likely and treatment may be delayed. However if there is only a thin covering, immediate treatment is required to prevent meningitis. The spinal lesions are most commonly found in the lumbosacral region. In some cases, the meningocele may protrude into the pelvis through a defect in the sacrum. This is associated with constipation and genital track anomalies.

Myelomeningocele is the most severe and most common form of spina bifida cystica. It occurs when both the meninges and the neural tissue herniate through a malformation of the vertebrae. In severe cases, the neural plate can be visualized as a raw, fleshy plate through a defect in both the vertebrae and integument. Nerve impulses are attenuated at the site of the lesion, which most commonly occurs at the lumbar or lumbrosacral region. The clinical effects depend on the location and size of the lesion. Higher lesions show increased levels of morbidity, decreased intelligence and greater disability. Myelomeningocele generally results in disturbances in motor, sphincter, and bladder function. Furthermore, lack of fetal movement in utero may result in orthopedic abnormalities of the lower extremities. Hydrocephalus and associated type II Chiari malformations are seen in 75% of myelomeningocele cases. Hydrocephalus, an excessive amount of CSF, is due to an obstructed ventricular system and may lead to increased intracranial pressure. The risk of hydrocephalus increases with higher lesions, however, the possibility of developing hydrocephalus should be considered regardless of level of lesion.

Anencephaly is a congenital defect resulting from a failure of closure of the anterior neuropore. This results in an extremely underdeveloped brain, usually consisting of only the residue of the brainstem, a hypoplastic pituitary gland and lacking the cerebral hemispheres and cerebellum. Anencaphaly is commonly associated with other malformations. Liveborn infants with this condition are rare and do not survive beyond the first few weeks.

Encephalocele is the herniation of the cranial contents through a defect in the skull. Less severe cases involve herniation of only the meninges, while more severe cases involve both the brain and meninges. Survival rate is high for liveborn infants and death usually occurs within the first 24 hours for infants who die. Encephalocele commonly occurs with associated malformations, particularly cerebral malformations. Hydrocephalus (described in myelomengocele) occurs in one-half of occipital encaphalocele legions. The extent of disability in survivors depends on extent of lesion and associated malformations. If the lesion involves only the meninges, the patient may develop normally, without mental or motor impairments. More severe lesions may result in disabilities such as mental retardation, ataxia, seizures, and blindness.

3. Etiology and Risk Factors:

The cause of NTDs is unknown, however certain environmental and dietary factors and a genetic predisposition have been noted.

Folic acid deficiency: Folic acid plays a role in synthesis of nucleic acids and certain amino acids and is essential for cell division. Diets deficient in folic acid have been associated with increased risk of all NTDs, while folate supplementation beginning prior to conception and through the first trimester notably decreases risk of NTDs.

Vitamin B12 deficiency: Pregnancies complicated by NTDs have a decreased serum vitamin B12 level, though this requires further study.

Environmental factors: Certain drugs (including valproic acid, carbamazepine, and folic acid antagonists), hypothermia, diabetes mellitus and obesity have been linked to increased frequency of NTDs.

Genetic Factors: Genetic factors in development of NTDs are not well defined. Genes involved in folate metabolism and transport have been studied and variation in several of these genes appear to confer risk of NTDs. No single, causal, gene has been has been identified in humans, though mutations in Scrb1 cause NTDs in mice.

4. Prenatal screening and diagnosis

Maternal serum Alpha-fetoprotein (AFP) screening: Screening for elevated maternal serum AFP is efficient for detection of spina bifida cystica and anencephaly, but not spina bifida occulta. Maternal serum is screened at 15 to 20 weeks gestation. AFP levels 2.0 to 2.5 times above the median level are considered abnormal and requires further evaluation

Ultrasound diagnosis: Routine ultrasound examination in the second or third trimester provide highly accurate diagnosis. However, some NTDs may be missed depending on the size and location of the defect, the position of the fetus, the volume of amniotic fluid, maternal habits and the skill and equipment of the sonographer.

Amniocentesis diagnosis: In cases of ambiguous ultrasound results, amniocentesis may be necessary. Elevated levels of both AFP and acetylcholinesterase in the amniotic fluid are indicative of spina bifida cystica.

Current literature recommends maternal AFP screening followed by ultrasound and amniocentesis if the screen is positive. Amniocentesis is not required when the ultrasound is able to provide a conclusive diagnosis.

5. Outcomes:

The prognosis of children with spina bifida depends on the severity and level of the lesion, management decisions as well as associated central nervous system anomalies. Complications of spina bifida vary according to severity but can include bladder dysfunction, fecal incontinence, infections, orthopedic problems, hydrocephalus and poor brain development. Children will often require shunts to treat the hydrocephalus.

With aggressive therapy, most patients (~85%) survive the neonatal period. Long term survival may be related to the need for CSF diversion. New studies are being conducted looking at outcomes of children who receive intrauterine repair of their NTD.

Reference

Carr J, Althea P, Miles H. The GLC Spina Bifida Survey: follow-up at 11 and 12 years. London, 1983.

Fishman, MA, Villarreal, GB. Myelomeningocele. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2008.

Hochberg, L, Stone, J. Prenatal screening and diagnosis of neural tube defects. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2008.

Kleigman RM, Marcdante KJ, Jenson HB, Behrman RE. Nelson Essentials of Pediatrics 5th Edition. Elsevier Saunders, 2006.

McMillan, JA, Feigin, RD, Oski, FA, Jones, MD. Oski’s Pediatrics: Principles & Practice. Lippincott Williams & Wilkins, 2006.

Acknowledgements

Written by: Jesse Bittman

Edited by: Anne Marie Jekyll