Spinal Dysraphisms

Summary

This chapter reviews open and closed neural tube defects. We discuss imaging evaluation as well as physical exam findings. Finally, we discuss current trends in treatment and perinatal care.

Introduction

Neural tube defects (NTD) are the second-most common birth defect after congenital heart defects, affecting 1-2 in 1000 pregnancies worldwide. Spinal dysraphisms are a subset of neural tube defects and are classified as open or closed. The most common open spinal dysraphisms are meningocele and myelomeningocele. Closed spinal dysraphisms include a wider range of conditions, including spina bifida occulta, tethered cord, lipomyelomeningocele, split cord malformations, neuroenteric cyst, and several other conditions. Although open spinal dysraphisms are usually compatible with postnatal survival, they can result in severe neurologic impairment correlating with the level of the lesion: inability to ambulate, urinary incontinence, hydrocephalus, scoliosis, and gastrointestinal (GI) disorders. Closed spinal dysraphisms are often less severe and sometimes asymptomatic but can cause severe neurologic impairment secondary to spinal cord tethering. Given both the neurologic complexity and severity of these conditions, it is paramount to understanding the embryology, screening, management, and treatment to offer the best neurologic outcome for these patients.

Embryology

Understanding the embryology of spinal dysraphisms has helped in making advancements to improve the technology used when treating patients with spinal dysraphisms. Spinal dysraphisms result from a failure of one of the following processes: gastrulation, primary neurulation, disjunction, or secondary neurulation. Gastrulation is the process by which the bilaminar embryonic disc becomes trilaminar: consisting of mesoderm, endoderm, and ectoderm. When gastrulation occurs, a neuroenteric canal forms, creating a temporary connection between the dorsal and ventral surface of the trilaminar disc. Conditions such as split cord malformations and neuroenteric cysts are thought to arise from a persistent neuroenteric canal. Neurulation begins with the notochord-inducing formation of the central nervous system by signaling the ectodermal tissue to differentiate into the neuroectoderm and form the neural plate. The neural plate then folds inward until the edges of the plate contact one another, a process referred to as primary neurulation. Primary neurulation is thought to be initiated at multiple closure sites and proceeds in a zipperlike fashion, bidirectionally. At the end of primary neurulation, the neural tube separates from the surface ectoderm in a process called disjunction. During disjunction, the mesoderm migrates between the surface ectoderm and neural tube, forming the meninges, vertebrae, skull, and paraspinal muscles. Premature or incomplete disjunction can lead to lipomyelomeningocele and dermal sinus, respectively. Secondary neurulation represents the formation of spinal cord caudal to the midsacral region. During this process, multipotent cells come together to form a tail bud, which undergoes canalization to form the secondary neural tube. Open spinal dysraphisms result from a severe delay or cessation of the progression of primary neurulation along the body axis. When the neural fold does not close properly the sclerotome is unable to cover the neuroepithelium, and a bifid vertebral canal results, leading to an open spinal dysraphism. Although unclear, it is believed that some closed spinal dysraphisms are a result of abnormalities of secondary neurulation, causing malformation of the lower sacral and coccygeal regions. This is thought to be the case, because these dysraphisms do not open to the external environment, resulting in tethering of the spinal cord because of faulty tissue separation, and the cell types contained within these dysraphisms usually have multiple germ layers, owing to the multipotential nature of the tail bud formed in secondary neurulation.

Several signaling pathways and cellular functions are involved in the development of neural tube defects; these include planar cell polarity signaling (PCP), sonic hedgehog signaling (SHH), bone morphogenic signaling (BMP), grainyhead-like genes (GHRL), retinoid signaling (RA), and many cellular functions such as apoptosis and cellular proliferation. Several factors are responsible that can increase the risk of developing neural tube defects and include both environmental and genetic factors. Environmental factors that affect the embryology of the central nervous system (CNS) and lead to an increased risk of development of NTDs include valproic acid, fumonisin (a fungal product), carbamazepine, trimethoprim, folate or vitamin B12 deficiency, inositol, and maternal diabetes mellitus. Genetic factors include the C67TT and a1298C polymorphisms of the gene methylenetetrahydrofolate reductase, which result in a 1.8-fold increased risk of NTDs and several modifier genes.

Pathology

Understanding the pathology of spinal dysraphisms is important in diagnosis and management, including both surgical and nonsurgical treatments. Spinal dysraphisms are typically divided into open and closed dysraphisms. Open dysraphisms include meningocele and myelomeningocele ( Table 58.1 ).