Kevin R. Moore

Embryology and Developmental Anatomy

Formation of the spine begins early in gestation, commencing at the end of the second gestational week with formation of the Hensen node and continuing into the beginning of the third week with the appearance of the neural plate during gastrulation. The notochordal process forms at day 16 or 17, with transient communication of the amnion through the notochordal canal to the yolk sac and through the neurenteric canal of Kovalevsky. The spine develops in a mostly orderly progression, and the vertebral axis and spinal cord develop synchronously. The rostral spinal cord (to about the level of S2) forms by the process of primary neurulation, whereas the caudal spinal cord (below the S2 level) forms by secondary neurulation, also referred to as canalization and retrogressive differentiation. Most congenital spinal anomalies can be explained by one or more events going awry during these processes.

The neural tube folds and closes at the end of the third gestational week, during primary neurulation; this leaves temporary cranial and caudal openings called neuropores. Normal neural tube closure by day 25 to 27 signals the end of primary neurulation. Meanwhile, the neural tube separates from the overlying ectoderm during the related process of dysjunction. If dysjunction occurs prematurely, perineural mesenchyme is permitted access to the neural groove and ependymal lining. This mesenchyme may differentiate into fat and prevent complete neural tube closure, which leads to the lipomatous malformation spectrum. If dysjunction fails to occur (nondysjunction), an ectodermal–neuroectodermal tract forms that prevents mesenchymal migration. Nondysjunction results in posterior dysraphism, producing the open neural tube defect spectrum of myelomeningocele (MMC), dorsal dermal sinus, and myelocystocele.

The neuroepithelial cells (neuroblasts) around the inner neural tube form the mantle layer, which produces the spinal cord gray matter. The outermost layer forms the marginal layer, which subsequently myelinates to produce the spinal cord white matter. The central neuroepithelial cells differentiate into ependymal cells along the central canal. Neural crest cells along each side of the neural tube form the dorsal root ganglia (DRG), autonomic ganglia, Schwann cells, leptomeninges, and adrenal medulla.

Concurrent with the neural tube folding during primary neurulation, spinal cord development below the caudal neuropore commences within the pluripotent tissue at the caudal eminence in the process of secondary neurulation. The initially solid cell mass canalizes and becomes contiguous with the rostral neural tube that was formed by primary neurulation. By day 48, a transient ventriculus terminalis appears in the future conus. If this persists after birth, it is noted incidentally as a normal variant ventriculus terminalis (“fifth ventricle”), usually of no clinical significance (see Chapter 40). Failure of proper secondary neurulation leads to caudal spine anomalies in the caudal regression, tethered cord, or sacrococcygeal teratoma (SCT) spectra in addition to terminal myelocystocele and anterior sacral meningocele (ASM).

By the third gestational month, the spinal cord extends the entire length of the developing spinal column. In fact, the more rapid elongation of the vertebral column and dura relative to the cord produces the apparent ascent of the cord during the remainder of gestation. Most importantly, the conus should be at adult level soon after birth, and persistent cord termination below L2–L3 after the first month of life in a full-gestation infant is probably abnormally low-lying.

Occurring simultaneously with spinal cord development is vertebral formation. During neurulation, the notochord induces the surrounding paraxial mesoderm derived from the primitive streak to form paired somite blocks (myotomes, sclerotomes). The myotomes form the paraspinal muscles and skin cover, and the sclerotomes divide into medial and lateral formations to produce the vertebral bodies, intervertebral disks, meninges, spinal ligaments (medial), and posterior spinal elements (lateral). Failure of correct notochordal induction leads to incomplete splitting of the neural plate from the notochord, producing the split notochord syndromes (neurenteric cyst and diastematomyelia [DSM]).

From day 24 until the fifth week, sclerotomal resegmentation commences, during which a horizontal sclerotomal cleft appears in the vertebra, and the caudal half of one vertebra combines with the rostral half of the vertebra below to form a “new” vertebral body. The notochord within the vertebral body degenerates, and the intervertebral notochord remnant becomes the intervertebral disk nucleus pulposus. Between days 40 and 60, the vertebrae undergo chondrification followed by subsequent ossification at distinct centers within the vertebral body and arches. This process continues past birth and into young adulthood. Ossification begins in the lower thoracic and upper lumbar regions and diverges cranially and caudally. In the cervical region, the vertebral primary ossification centers appear after the neural arch centers, beginning in the lower cervical spine (C6, C7) and proceeding rostrally. Aberrances occurring during the chondrification and ossification process produce myriad segmentation and fusion anomalies (SFAs; hemivertebrae, butterfly vertebrae, block vertebrae).

Spinal Dysraphism

Congenital spinal anomalies are classified both by clinical appearance (presence or absence of back mass) and by embryologic origin. Because the embryologic approach is easier to conceptualize, it will be emphasized here.

Spinal dysraphism is a broad term that encompasses a variety of disorders that have as a common feature abnormal dorsal spine formation; it is defined as incomplete or absent fusion of midline mesenchymal, bony, and neural structures. This term refers to large spinal defects, and not to the common spina bifida occulta, in which there is only a small cleft within a spinous process or a minor incomplete fusion of laminae at L5 or S1. Use of the term spina bifida occulta is strongly discouraged in favor of the preferred term incomplete posterior element fusion, because this finding is generally incidental and without clinical significance.

The osseous abnormalities associated with true spinal dysraphism may involve multiple vertebrae. Spina bifida (Latin, “cleft into two parts”) is characterized by incomplete neural arch fusion with absence of all or parts of the affected posterior elements (laminae and spinous processes). Associated segmentation anomalies of the vertebral bodies—such as hemivertebrae, butterfly vertebrae, and block vertebrae—may be present.

Children with spinal dysraphism may come to medical attention with a back mass, abnormal cutaneous manifestations, gait disturbance, and bowel and bladder incontinence. Classically, spinal dysraphism is classified into two categories, based on the clinical presence or absence of a back mass. The first category is spinal dysraphism with back mass that is not covered by skin (e.g., spina bifida aperta or cystica, MMC, myelocele); the second is spinal dysraphism with skin-covered back mass (e.g., lipomyelomeningocele [LMMC], myelocystocele, dorsal meningocele).

Abnormalities of Primary Neurulation

Primary neurulation abnormalities result from premature dysjunction, nondysjunction, or a combination of both.

Anomalies of the Caudal Cell Mass

Caudal cell mass anomalies are a diverse group of anomalies that result from aberrant secondary neurulation, postulated to be an insult to the caudal cell mass before the fourth gestational week. Most cases are sporadic, although a dominantly inherited defect in the HLXB9 gene has been described. The mothers of 15% to 20% of these infants are diabetic, the offspring of 1% of diabetic mothers are afflicted, and an association has been found with VACTERL syndrome (vertebral, anal atresia, cardiac, tracheal, esophageal, renal, limb), omphalocele, bladder extrophy, imperforate anus, and the Currarino triad. The range of severity is substantial, from clinically unapparent mild dysgenesis to absence of the lower body.

Hypogenesis or agenesis of the caudal cell mass produces caudal regression syndrome (CRS; Fig. 43-6). Two types are described. The more severe CRS, type 1, features a foreshortened terminal vertebral column, high-lying wedge-shaped conus termination, and more severe associated visceral and orthopedic anomalies. The less severe CRS, type 2, has a low-lying tethered spinal cord with milder associated malformations. In general, the higher the cord termination, the more severe the sacral anomalies. The most severe CRS presentations are lumbosacral agenesis, in which the spine terminates at the lower thoracic level, and severe sacral dysgenesis, with fused lower extremities in a “mermaid” configuration (sirenomyelia). In contrast, the mildest CRS cases may manifest merely as a missing terminal sacral segment identified on imaging that is clinically asymptomatic. CRS is associated with myriad other visceral abnormalities, including renal or pulmonary hypoplasia and anorectal malformations. Other commonly associated spinal malformations include open dysraphism, vertebral SFAs, and split-cord malformations.

Segmental spinal dysgenesis (SSD) is a very rare dysraphic anomaly characterized by segmental thoracolumbar or lumbar vertebral and spinal cord dysgenesis or agenesis. Congenital thoracic or lumbar kyphosis is characteristic, with a palpable dorsal bone spur located at the gibbous apex. The upper spinal cord is normal, but the cord segment below the dysgenetic segment is bulky, thickened, and low-lying. The spinal canal proximal and distal to the dysgenetic level is of normal caliber. Some authors believe that SSD and CRS represent different phenotypes along a single malformation spectrum, and that spinal morphology depends on the level of developmental disruption. If development is affected distally, CRS results, but if the lesion occurs more proximally, SSD is observed.

Perhaps the most common entity within the caudal cell mass dysplasia spectrum is tethered cord syndrome (TCS), which manifests clinically as gait spasticity, low back and leg pain that is worse in the morning, lower extremity sensory abnormalities, and/or bladder difficulties. TCS patients are most likely to come in during periods of rapid somatic growth. TCS refers strictly to patients with a low-lying cord and thickened filum, not those with other spine and cord abnormalities, although in fact those patients may be similar in clinical presentation and may be considered “tethered.” It is important to consider TCS a distinct clinical diagnosis, with imaging relegated to the role of preoperative planning rather than establishing the primary diagnosis. On imaging, TCS manifests either as a taut spinal cord without definitive conus or a low-lying conus (Fig. 43-7). The filum is frequently thickened and shortened, and an associated terminal lipoma may be present. Symptomatic patients may benefit from surgery, but it is crucial to exclude other associated anomalies before surgery.

Two other important rare presentations of caudal cell mass dysplasia are the ASM and the terminal myelocystocele. ASM features a large anterior meningocele outpouching that traverses an enlarged sacral foramen and produces a presacral cystic mass. This may be clinically mistaken for a SCT and may prompt neuroimaging. Most ASMs are sporadic, but a minority show an inherited predisposition within the Currarino triad or in syndromes that feature dural dysplasia, such as neurofibromatosis type 1 (NF1) and Marfan syndrome. As with other caudal cell mass dysplasias, additional congenital abnormalities may be found, such as anorectal malformations, caudal dysgenesis, and dermoid or epidermoid cysts. Fortunately, imaging is highly characteristic in the more common simple form, with a presacral cystic mass that connects to the thecal sac through an enlarged sacral neural foramen (Fig. 43-8). Complex ASMs with fat or neural elements are also recognized by their extension through the neural foramen. Terminal myelocystocele is a very rare malformation that manifests as a hydromyelic spinal cord that traverses a meningocele to terminate in a skin-covered myelocystocele (e-Fig. 43-9). These abnormalities are rarely imaged, until the infant survives the commonly associated anorectal and visceral anomalies that drive early management and produce most of the morbidity and mortality. Infants with terminal myelocystocele may be neurologically intact at birth but subsequently lose neurologic function.

Finally, if the primitive streak incompletely regresses and leaves a caudal totipotential cell rest remnant, an SCT (Fig. 43-10) may result. SCTs demonstrate tissue from all three cell layers and contain varying proportions of mature and immature elements. These are surgically graded, according to the American Academy of Pediatrics (AAP) classification, based on proportion of internal (pelvic) and external components; prognosis is determined by the AAP grade and by the presence or absence of mature or malignant components. External tumors, mature elements, and younger patient age predict a better outcome. The surgeon must resect the coccyx to prevent recurrence. Fetal and early infancy morbidity and mortality are related mostly to cardiac failure from intratumoral shunting and associated visceral anomalies, whereas later mortality is related to lesion malignancy.

MRI is the best modality for preoperative planning and staging for all caudal cell mass anomalies. Computed tomography (CT) has a more limited role, such as in screening for visceral organ anomalies or evaluating bones. Ultrasonography may be helpful for initial newborn screening, because it can be performed portably in the newborn nursery or intensive care nursery, thereby eliminating transport issues in unstable infants, but it usually does not provide all the necessary information for surgical planning.

Anomalies of Notochord Development

Neurenteric cyst (e-Fig. 43-11) consists of an intraspinal cyst lined by enteric mucosa, and it is most common in the thoracic spine, followed by the cervical spine. Such cysts putatively arise from an abnormal connection between primitive endoderm and ectoderm that persists beyond the third embryonic week. Whereas normally the notochord separates ventral endoderm (foregut) and dorsal ectoderm (skin, spinal cord) during embryogenesis, in a neurenteric cyst, a separation failure “splits” the notochord and hinders the development of mesoderm, which traps a small piece of primitive gut within the developing spinal canal. This gut remnant may become isolated, forming a cyst, or it may maintain connections with gut or skin (or both); this produces the spectrum of fistulas and sinuses that constitute the spectrum of dorsal-enteric spinal anomalies. The most severe malformations remain in communication through the primitive vertebral osseous canal of Kovalevsky, but even mild cases usually show some vertebral segmentation anomalies on close inspection. Multiplanar MRI best demonstrates the cyst and its relationship to the spinal cord, as well as connections to the mediastinal or abdominal viscera. CT, particularly with multiplanar and three-dimensional reformats, optimally demonstrates osseous vertebral anomalies for preoperative planning.

DSM arises from an aberrant process similar to that of the neurenteric cyst and results in a splitting of the spinal cord into two hemicords, each with one ventral and one dorsal root. The hemicords may be symmetric, or they may be asymmetric, known as partial DSM; one or both may feature hydromyelia or be tethered. The much rarer (perhaps mythical) diplomyelia, or duplicated spinal cord, is the only other differential entity to consider; it occurs probably in the context of a duplicated spinal axis, and many authorities think it most likely represents a very severe DSM rather than true spinal cord duplication.

Because the notochord influences vertebral development, vertebral segmentation anomalies are very commonly associated with DSM. Therefore important factors for preoperative planning include the presence (type 1 DSM; Fig. 43-12) or absence (type 2 DSM; Fig. 43-13) of an osseous or fibrous spur and whether the cords reside in separate or single dural tubes (see also Chapter 42). Occasionally in type 2 DSM, a nerve root or roots may become adherent to the dura and may tether the spinal cord, producing the meningocele manqué. DSM may be isolated or found in conjunction with other spinal anomalies, particularly MMC, thus it is critical to search for DSM before any spinal anomaly repair or scoliosis correction. A patient with MMC whose symptoms progress after surgical closure is a relatively common presentation of undiagnosed DSM. Cutaneous abnormalities such as skin dimples or discoloration, vascular lesions, or hair patches are sometimes present and can guide attention to the most likely level of DSM.

Other Congenital and Developmental Anomalies

Other uncommon but important congenital spinal anomalies whose etiology is not definitively known include the simple dorsal meningocele and the lateral meningocele.

Dorsal meningoceles (e-Fig. 43-14) by definition occur dorsally, most often over the lumbosacral spine, and feature a skin-covered meningocele devoid of neural elements that protrudes through a posterior dysraphic defect. In practice, however, it is not uncommon to find a dysplastic nerve root or other neural tissue within a meningocele.

Lateral meningoceles (e-Fig. 43-15) manifest as paraspinal masses filled with cerebrospinal fluid that are contiguous with the thecal sac and extend through the neural foramen, with adjacent pedicular and foraminal osseous remodeling. They are generally “simple,” but some may contain fat or neural tissue and are then better termed “complex.” Important associations include Marfan syndrome and NF1.

In both anomalies, multiplanar MRI is the best modality to demonstrate the soft tissue components. CT is helpful for clarifying the osseous anatomy, and usually this is done before surgery. If MRI is contraindicated or inconclusive, CT myelography can demonstrate the meningocele and confirm its continuity with the dural sac.

Vertebral Formation and Segmentation Anomalies

Anomalies of vertebral formation and segmentation arise from aberrancies in vertebral column formation. These are generally divided into anomalies that result from either partial or total failure of vertebral formation (Fig. 43-16) and failure to correctly segment after vertebral formation (vertebral segmentation failure; e-Fig. 43-17). The abnormal vertebra may be supernumerary, or it may replace a normal vertebral body. Abnormal PAX1 expression is a postulated etiology in the development of segmentation anomalies, and other visceral and neuraxis anomalies are also commonly identified. More severe SFAs tend to have a higher incidence of concurrent visceral organ or other neuraxis anomalies. The degree and location of vertebral formation failure predicts morphology; unilateral chondral center deficiency and failure of ossification produces a hemivertebra, whereas central failure of ossification centers to unite produces a butterfly vertebra. Conversely, vertebral segmentation failure presents with composite or “block” vertebra and posterior element fusions (Fig. 43-18). Not surprisingly, block vertebrae frequently coexist with hemivertebrae and butterfly vertebrae (Fig. 43-19), leading many to lump these various vertebral anomalies together into the working term SFAs. Many clinical syndromes prominently feature SFAs, including Klippel-Feil and Jarcho-Levin (spondylothoracic dysplasia) syndromes. Therefore SFAs are not findings that confirm a specific disorder, but rather they are imaging markers that prompt further consideration of a possible syndromic process.

Conclusions

Pediatric congenital spinal anomalies demonstrate myriad variations and are potentially confusing. However, with understanding of simplified spinal embryology and anatomy, it is usually possible to identify a few characteristic features that permit a more specific diagnosis and alert for other possible associated anomalies.

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