Neural Tube Disorders

Neural tube defects are the most common severe central nervous system anomalies, second only to cardiovascular abnormalities in causing congenital morbidity and mortality. The nervous system is ectodermal in origin. The central nervous system consists of the brain and spinal cord formed by folding of dorsal part neural plates under the influence of underlying notochord and prechordal mesoderm and closure anterior (cranial) and posterior (caudal) neuropores by a process called neurulation that begins as early as 3 and 4 weeks of conception—failure to complete neurulation results in neural tube defects (NTDs). Neurulation consists of two phases; primary and secondary neurulation. Primary neurulation is defined as folding the dorsal part of the neural tube and lengthening of neural plates in the longitudinal axis, and narrowing the cross-section by the phenomenon called convergent extension forming the brain and spinal cord. Primary neurulation is followed by canalization of neural tubes, forming the distal part of the spinal cord by a process called secondary neurulation.

Fibroblast growth factor (FGF) signaling concordant with suppression of bone morphogenetic protein 4 (BMP4), which is a transforming growth factor, induces neural plate formation. Also, retinoic acid organizes the cranial-caudal axis by regulating the expression of homeobox genes. Neural tube defects can be present anywhere from the brain to the end of the spinal cord. Open NTDs are due to failure of primary neuralation and associated with hydrocephalus, Chiari II malformation, etc. Neural tissue is exposed to and associated with cerebrospinal fluid (CSF) leakage. Closed NTDs are due to failure of secondary neuralation and are generally confined to the Spinal cord. Neural tissue is not exposed. The closed neural tube defects occur post neurulation and include lipoma with a dorsal defect (lipomyelomeningocele, lipomyelocele), especially when a subcutaneous mass is present. Common variants of NTDs are as follows:

1. Spina bifida occulta: failure of caudal neuropore to close. The spinal cord, meninges, and overlying skin remain intact, with no herniation.

2. Spina bifida cystica: meningocele (herniation of meninges only) and myelomeningocele (herniation of both meninges and neural tissue)

3. Myeloschisis: exposed neural tissue without skin or meninges covering.

4. Anencephaly: failure of rostral neuropore to close; thus, the brain and cranial vault are grossly malformed with normal hindbrain development.