CHAPTER 38 SPINE AND SPINAL CORD: DEVELOPMENTAL DISORDERS

Valerie S. Tay, Andrew Kornberg, Mark Cook

Developmental disorders of the spine and spinal cord occur because of defects in the development and maturation of the nervous system. A basic understanding of embryology is therefore important in appreciating the nature and scope of these disorders. There are various ways of approaching and thinking about the developmental disorders:

1. Clinicoanatomical: This is a logical viewpoint because the anatomical defect is correlated with the neurological impairment, disabilities experienced, and overall functional outcome. Disorders can be classified anatomically on the basis of the structures (e.g., bony elements, supporting soft tissues, or neural elements) or the level of the neuraxis involved. Clinically, the developmental disorders of the spine and spinal cord can manifest in various domains, and clinical features can generally be thought of as neurological or myelopathic, as orthopedic and biomechanical, or as multisystem features of a widespread developmental disorder.

2. Molecular genetics: In the area of developmental disorders, research into the molecular genetics is increasingly important in advancing knowledge of the mechanisms underlying these disorders, in reclassifying the syndromes, and in providing a common link between some of the disorders.

As knowledge and understanding of these disorders continue to expand, the most reasonable approach is to integrate advances in genetic and etiological models within the traditional phenotypic clinicoanatomical framework. Developmental disorders can be classified anatomically, depending on whether they affect primarily the spinal cord and neural tissues or the spine and supporting structures (Table 38-1).

TABLE 38-1 Developmental Disorders That Can Affect Vertebrospinal Structures

Disorders Affecting the Spine	Disorders Affecting the Spinal Cord and Neural Tissues	Vascular Malformations
Disorders of the craniovertebral junction, including: Klippel-Feil anomaly Basilar invagination and platybasia Occipitalization of the atlas Congenital atlantoaxial dislocation	Chiari malformation Syrinx Neural tube defects Split cord malformations Sacral agenesis Tethered cord syndrome Lipomas Tight filum terminale Dural bands Congenital sinus tracts and intraspinal dermoid, epidermoid	A variety of vascular malformations can affect the spine and spinal cord
Scoliosis	Developmental cysts

There is a wide spectrum of developmental disorders affecting the spine and spinal cord, ranging in age at presentation, in clinical manifestations, and in severity. Although more likely to manifest in the pediatric population, some milder forms may manifest later in life as well. Neurologists for both pediatric and adult populations should have an awareness and appreciation of the range and manifestations of these disorders. The aim of this chapter is to provide a broad overview and appreciation of the developmental disorders affecting the spine and spinal cord, with a few select disorders covered in greater depth. A host of vascular malformations and metabolic conditions may affect the spine and spinal cord; they remain, however, beyond the scope of this chapter and are not discussed.

NORMAL DEVELOPMENT OF THE NERVOUS SYSTEM

The human embryonic period spans the first 8 postfertilization weeks and is classified on the basis of a morphological system. There are 23 distinct Carnegie stages, each stage covering a period of 2 to 3 days. This staging system facilitates an understanding of the timing and sequence of embryonic development. The fetal period spans the 9th week after fertilization to birth. Fetal age is thought of mainly as measurements, inasmuch as a similar morphological staging system is not available. The great majority of congenital malformations begin during the embryonic period.¹^–³

The neural tube is the embryonic structure that develops into the brain and spinal cord. Primary neurulation refers to the development of the neural tube from the neural plate. Complete development and closure of the neural tube occurs from days 17 to 30 after conception and spans Carnegie stages 8 to 12 in the embryonic period (Table 38-2). The caudal eminence is the continuation of the primitive streak and develops into the terminal portions of the notochord, somites, vertebrae, and hindgut. The neural cord arises from the caudal eminence and forms the caudal portion of the spinal cord. This process is secondary neurulation. The level of the junction between primary and secondary neurulation is at the level of the future second sacral vertebra. There is elongation of the previous neural tube together with formation of the lower sacral and coccygeal segments. This part of the development of the nervous system commences in stage 12 at 4 weeks and ends approximately at stage 20.²^–⁶

TABLE 38-2 Important Stages in Primary Neurulation and the Formation and Closure of the Neural Tube

Development Stage No.	Days in Embryonic Life	Nervous System Development
8	17-19	Development of the neural plate
9	19-21	Development of the neural folds
10	22-23	First steps in the fusion of the neural folds: There are two initial sites of fusion: fusion proceeds bidirectionally from the lower medullary rhombencephalic site and in a caudal direction from the higher prosencephalic site. The fusions terminate in two neuropores: the rostral and caudal neuropores.
11	23-26	Closure of the rostral neuropore
12	26-30	Closure of the caudal neuropore

Based on a table from Lemire RJ: Neural tube defects. JAMA 1988; 259:558-562 Copyright © 1988 American Medical Association. All rights reserved; and on information from O’Rahilly R, Muller F: The two sites of fusion of the neural folds and the two neuropores in the human embryo. Teratology 2002; 65:162-170.

The vertebral bodies of the spine are generated from the mesenchymal cells. The process of gastrulation occurs at day 14 in embryonic life to generate the mesenchymal cells that will in turn develop into the head, cardiac, and the paraxial and lateral mesoderm. At 20 to 30 days in embryonic life, the paraxial mesoderm, in a process of somatogenesis, subdivides into spherical somite segments on each side of the spinal cord in a rostral-to-caudal direction. The somites first appear in stage 9; differentiation commences at stage 10. The somites mature and further subdivide into the sclerotome to form the vertebral bodies, the myotome to form the musculature, and the dermatome to form the dermis. The sclerotome undergoes a resegmentation process in which the caudal end of one somite links with the rostral end of the next somite to form a vertebral body.⁷^–⁹

DEVELOPMENTAL DISORDERS AFFECTING THE SPINE

The developmental disorders affecting the spine that are covered in this chapter include scoliosis and a cluster of disorders originating primarily at the craniocervical junction. Some of the other generalized spinal disorders, including metabolic disorders, are covered in other chapters.

Klippel-Feil Anomaly

Management

Diagnostic investigations center on imaging studies. Good-quality radiographs and computed tomographic (CT) scans of the cervical spine are necessary to show the extent of cervical fusion and to evaluate potential instability (Fig. 38-1). Magnetic resonance imaging (MRI) studies, including flexion and extension views, are useful for evaluating instability or stenosis in the cervical spine and for assessing neurocompression of the spinal cord. MRI should be performed on the whole neuraxis in order to look for the associated developmental anomalies. Further evaluation is targeted at the associated conditions, including audiology assessments and cardiac and renal investigations.⁸

Figure 38-1 Computed tomographic image of a Klippel-Feil anomaly. The coronal image (A) shows fusion of C2 and C3 and a large block fusion from C5 to T2. B, A three-dimensional reconstruction in the same patient.

Management depends on the symptoms and the presence of other malformations. Treatment modalities may include simple measures of modifying activities and the use of traction and bracing to alleviate deformities. Surgical intervention to stabilize the spine is indicated if there is neurological impairment or symptomatic cervical instability. Surgical options include occipitocervical arthrodesis and combined atlantoaxial and subaxial arthrodesis.⁸

Basilar Impression

Definition

Basilar impression (or basilar invagination) occurs when there is an abnormal upward displacement of the basilar and condylar portions of the occipital bone. This leads to invagination of the foramen magnum into the posterior cranial fossa with associated translocation of the upper cervical vertebrae into this depression. We believe the terms basilar impression and basilar invagination are interchangeable, but some authors differentiate basilar impression from basilar invagination on the basis of differences in anatomical definitions and causation (e.g., acquired or primary).^10,¹¹ Some texts include platybasia in the spectrum of basilar impression. Platybasia is an abnormal flattening of the base of the skull with an abnormally obtuse angle between the plane of the clivus and the plane of the anterior fossa. This may occur together with basilar impression but is of no real clinical significance.

Basilar impression has traditionally been defined on the basis of a deviation from set anatomical and radiological parameters:

1. Chamberlain’s line is drawn from the dorsal edge of the hard palate to the dorsal lip of the foramen magnum.

2. McGregor’s line is from the upper surface of the posterior edge of the hard palate to the lowest level of the occipital bone.

3. McRae’s line is a line from the anterior to the posterior border of the foramen magnum.

4. Bull’s angle is an angle at the intersection of the plane of the hard palate and the plane of the atlas (line formed by joining the midpoints of the anterior and posterior arches of the atlas). The normal upper limit for this angle is 13 degrees.

For instance, if Chamberlain’s line is the defining parameter, basilar impression is present when more than one third of the odontoid process lies above this line.^10,¹²

Epidemiology

Basilar impression is the most common of the craniocervical malformations; clinical manifestations usually occur from the second decade onward.¹¹ The true incidence is unclear.

Clinical Features

Basilar impression may be asymptomatic or may manifest with deformities, including a shortened neck. Movement or exercise-induced occipital headache is a common feature. Oculomotor features include horizontal and upward-beat or downward-beat nystagmus. Other cranial nerve symptoms include facial nerve spasm, trigeminal sensory symptoms, and trigeminal neuralgia. Pontomedullary compression can lead to pyramidal tract signs, with the lower limbs typically more affected than the upper limbs. Sleep apnea and respiratory depression have been described.^11,¹²

Primary basilar impression is often associated with other developmental anomalies, including occipitalization of the atlas, the Klippel-Feil anomaly, the Arnold-Chiari malformation, and syringomyelia or syringobulbia.¹²

Etiology and Pathophysiology

Neurological manifestations occur in basilar impression as a result of direct compression on the brainstem and of vascular abnormalities. Basilar impression can be classified on the basis of etiology into two categories:

1. Primary basilar impression, a primary developmental defect with a familial tendency in which there is no underlying bone abnormalities.

2. Secondary basilar impression, in which an underlying generalized bone disorder leads to bone softening. Secondary basilar impression has been described with achondroplasia, osteogenesis imperfecta, osteomalacia, hyperparathyroidism, Paget’s disease, Hurler’s syndrome, and Hajdu-Cheney syndrome.^11,¹²

Management

Imaging studies are necessary to fully evaluate basilar impression and associated anomalies. CT scans are useful in reviewing the bony anatomy, whereas MRI is particularly useful in evaluating neural structures for neurocompression, cerebellar tonsillar herniation, and syrinx. Other investigations for an underlying systemic disorder include measurements of calcium, phosphate, and alkaline phosphatase.

The treatment goal is to relieve current compression, and to prevent future compression, of the neuraxis. The treatment modalities for symptomatic basilar impression include cervical traction and surgical intervention. Cervical traction has been reported to cause vertebral artery dissection, as well as potentially causing infection, cranial fractures, and hemorrhage. Anterior compression is managed with an anterior surgical approach; posterior or circumferential compression is managed with a posterior approach. The role of prophylactic surgery or prolonged immobilization with asymptomatic lesions is unclear.^10,¹²

Atlantoaxial Dislocation

Definition

A variety of congenital anomalies can affect the atlantoaxial junction and cause atlantoaxial dislocation. These anomalies include the following:

1. Congenital C1 anomalies, which may include partial or complete agenesis or dysgenesis of the posterior arch and hypoplasia of the atlas with an intact arch.¹⁴

2. Abnormalities of the dens, including hypoplasia, bifid dens, and tripartite dens.

3. Os odontoideum, in which the odontoid process fails to fuse to the body of the axis.

Epidemiology

The various degrees of C1 malformations have a quoted prevalence rate of 4%, which is based on autopsy studies.¹⁴

Clinical Features

Abnormalities in this region may be asymptomatic and found incidentally, or they may manifest with pain. The vertebral anomalies may lead to atlantoaxial instability and dislocation. This may result in cervicomedullary compression, which may manifest either spontaneously or after trauma. Affected individuals are especially prone to cord compression during extension injuries: for instance, with intubation or after neck injuries. These anomalies should be considered when a child presents with a neurological deficit or neck pain after minor trauma.^14,¹⁵

Congenital atlantoaxial instability may be seen in association with Down’s syndrome. Other congenital craniovertebral junction and spinal disorders may occur in tandem as well, including Chiari type I and SCMs. It is important to be aware that atlantoaxial instability may not be congenital in nature but may be caused by an underlying condition, such as rheumatoid arthritis.^14,¹⁵

Etiology and Pathophysiology

The craniovertebral junction malformations arise from defects during the ossification process. The malformations lead to instability in the atlantoaxial joint with subsequent dislocation. Subluxation usually occurs in the horizontal plane, with C1 moving anteriorly to C2. In other settings, progressive cervical myelopathy rarely occurs above C2; the usual scenario of a myelopathy is in the context of acquired degenerative change and usually occurs below C3. The risk of neurocompression depends on the underlying malformation and the joint stability. The actual degree of neurocompression depends on the extent of the subluxation and the width of the spinal canal. The normal sagittal diameter of the spinal canal is 16 to 25 mm at the level of the atlas; the spinal cord is at risk when the canal diameter is less than 14 mm.¹⁴

Management

The use of high-quality imaging with plain radiographs, CT scans (including fine cuts), and MRI is necessary in the evaluation of atlantoaxial dislocation and craniocervical anomalies. Flexion and extension views are especially useful for assessing joint stability. MRI is crucial in the assessment of the neural structures, especially with regard to cord compression. Surgery is indicated in order to decrease the possibility that significant neurological deficits may develop and should be considered when there is neurocompression or when the individual is symptomatic. Surgery for atlantoaxial and craniocervical instability is a challenging field, especially because surgeons have to work with abnormal anatomy while taking into account the ongoing growth potential for the child. Depending on the underlying malformation, surgical management consists of decompression procedures and joint fusion and stabilization.¹⁴^–¹⁷

Scoliosis

Definition

Scoliosis is diagnosed on the basis of a 10-degree lateral curve with associated vertebral rotation. Scoliosis may be either primary (idiopathic scoliosis) or secondary. Neurogenic scoliosis is usually secondary to a developmental disorder, including the Chiari malformation, hydrosyringomyelia, and neural tube defects (NTDs).

Epidemiology

Idiopathic scoliosis affects 2% to 4% of children aged 10 to 16 years. The incidence is equal in boys and girls for curves of less than 20 degrees. Girls, however, significantly outnumber boys, at 5:1, for curves of more than 20 degrees. Secondary neurogenic scoliosis is more common in the younger population. For instance, of patients with the Chiari malformation and syringomyelia, 82% younger than 20 years have scoliosis, as opposed to only 16% of those older than 20 years.^18,¹⁹

Clinical Features

Individuals with scoliosis may present with back pain or, more obviously, with the spinal curvature deformity. In evaluating scoliosis, it is imperative to be aware that the spinal deformity may be the presenting feature of an underlying spinal cord or brainstem anomaly in 4% to 58% of affected patients. Individuals with scoliosis may present with the neurological or orthopedic features of the underlying developmental disorder.^18,¹⁹

Etiology and Pathophysiology

Secondary scoliosis is thought to arise from a generalized paresis of truncal musculature or congenital changes in the vertebrae. In addition, scoliosis in the Chiari-syringomyelia complex may be caused by the abnormal intramedullary pressures within the spinal cord that interfere with the postural tonic reflexes.^18,¹⁹

Management

It is important to treat or rule out an underlying spinal cord or brainstem disorder in a young patient with scoliosis. Evaluation includes the use of radiographs (Fig. 38-2) to chart the pattern of scoliosis and MRI to look for associated anomalies in the neural elements. Posterior fossa decompression for the Chiari-syringomyelia malformation can lead to an improvement in the scoliosis, especially if done early in the patient’s life. Initial treatment may involve use of a spinal orthotic brace as well. Spinal fusion surgery may ultimately be required for surgical correction of the scoliosis.^18,¹⁹