Spinal Disorders Associated With Connective Tissue Disorders

General Considerations

In patients with spine disorders associated with CTD, early onset and severity of spinal involvement necessitate early diagnosis and treatment, which poses challenges for spine growth and visceral function. Pediatric growth can be divided into three phases: (1) birth to 5 years of age, (2) 5 to 10 years of age, and (3) older than 10 years of age. Accurately predicting likely growth rate and identifying peak height velocity enables practitioners to intervene when there is a high risk of deformity progression and to cease preventive measures when there is growth cessation. Ways in which growth can be measured include measuring standing and sitting heights, T1 to S1 length, arm span, and the length of the thoracic spine. Spine growth is also correlated with pulmonary development. The size of the thoracic cage, for instance, is closely related to development of the lungs, which has implications for life expectancy and quality of life. Development of the lungs primarily takes place from birth to 8 years of age, which is when growth of the bronchial tree ends. Without adequate space, alveolar proliferation can terminate prematurely and lead to lifelong reduction in the number of functional alveoli. Therefore, interventions that stunt the growth of the thoracic spine during this period can be detrimental to pulmonary development. Growth-friendly options for treatment of early-onset scoliosis, such as traditional and magnetically controlled growing rods, can be used during this period.

Another important consideration is challenging anatomy in patients with CTDs. Surgeons can expect to encounter distortion of the spinal architecture, osseous fragility, and contracture, all of which serve to limit correction and imperil fixation. For instance, pedicles may be absent or insufficient for screw placement. To account for the anatomical distortion, the surgeon may require custom or modified implants. In addition, bone health must be taken into consideration. Patients with CTDs may present with potential fragility because of the nature of the disease, immobility, or inability to obtain adequate nutrition. Bone health can be assessed with dual-energy x-ray absorptiometry. In the pediatric population, bone mineral content that is “low for age” is defined as bone mineral content that is over two standard deviations lower than expected. Patients who have had one or more vertebral fractures in the absence of high-energy trauma or local disease, as well as patients whose bone density is low for age and who have a significant fracture history (at least one long bone fracture in the lower extremity or two long bone fractures in the upper extremity before 19 years of age or at least two long bone fractures before 10 years of age) meet the definition for pediatric osteoporosis.

Given the complexity of the comorbidities, the severity, and the rarity of each CTD, a multidisciplinary approach is necessary to optimize outcome for these patients with spinal disorders. Patients with CTDs are ideally cared for by a team of different specialists in conjunction with the surgical staff that includes respiratory, gastroenterology, and cardiology specialists, dietitians, physical and occupational therapists, neurologists, anesthetists, and nursing staff. Preoperative optimization and postoperative comanagement of patients with CTDs may have a significant impact on limiting perioperative complications of surgery. Pulmonary, cardiac, nutritional, and mobility comorbidities require optimization for safe surgical intervention, and the development of standardized protocols is valuable to ensure high-quality and comprehensive care.

Atlantoaxial Instability

One of the most well-known spinal disorders associated with CTDs in the pediatric population is AAI, which is defined as increased mobility of C2 in relation to C1. The atlas (C1) and axis (C2) are unique in their shape and function compared with the subaxial cervical vertebrae (C3–C7). C1, for instance, is comprised of three ossification centers (an anterior arch and two neural arches), whereas C2 is formed from four ossification centers (two for each neural arch, one for the dens, and one for the body). The atlantoaxial articulation is composed of three joints: the median atlantodental joint and the lateral atlantoaxial facet joints. Because the upper cervical spine is inherently unstable, the ligaments serve as the most important stabilizer for the atlantoaxial joint. Pediatric patients with CTDs can present with pathology that disrupts the ligamentous integrity of the C1–C2 junction.

Down syndrome is the most frequently encountered CTD associated with AAI. In the pediatric population, the incidence of AAI with Down syndrome ranges from 7.6% to 22%, whereas the incidence of symptomatic instability at the same junction can be as high as 2.6%. This is thought to be caused by collagen abnormalities that lead to ligamentous laxity, particularly of the transverse atlantal ligament (TAL) in Down syndrome ( Fig. 51.1 ).

Other conditions, such as Kniest dysplasia, mucopolysaccharidoses such as Morquio disease, and Larsen syndrome, are also associated with AAI and should have a lower threshold for diagnostic workup. Unlike Down syndrome, the AAI seen in mucopolysacchridoses and type II collagenopatheis (e.g., Kniest dysplasia) is caused by odontoid dysplasia. Therefore, evaluation should be performed with magnetic resonance imaging (MRI) instead of radiographs.

Because AAI is difficult to identify from clinical presentation, clinicians should be vigilant for the diagnosis in patients with the aforementioned CTDs and order anteroposterior (AP) and lateral views of the cervical spine, flexion and extension radiographs, and the odontoid open mouth view. Most cases of AAI are discovered incidentally. X-rays are typically the first imaging modality used for diagnosis. In the pediatric population, an atlantodental interval (ADI) of 5 mm or more on the lateral radiograph is indicative of instability. This is greater than the 3-mm adult value because there is increased cartilage content in C1 and C2. In patients with known AAI, the space available for the cord (SAC), which is defined as the distance between the posterior aspect of the odontoid and the anterior aspect of the atlas posterior ring, is a more useful measurement; neurological problems can be seen with a SAC of less than 13 mm. For patients whose x-rays are difficult to interpret, such as patients who are 5 years old or younger, an MRI (e.g., flexion-extension MRI) can be used to further evaluate attenuation of the TAL, ADI, and SAC. For patients with Down syndrome, AAI is attributed to connective tissue laxity, which can be seen through radiographs. For patients with mucopolysaccharidosis and type II collagenopathies, AAI is owing to odontoid dysplasia and should be evaluated with an MRI.

There is a wide range of treatment options for those diagnosed with AAI. For patients with recent or progressive neurological deficit, surgery with posterior cervical fusion is recommended. A posterior occiput–C2 fusion is indicated for AAI associated with atlantooccipital anomalies. In rare cases, nonoperative management may be elected by asymptomatic patients. In these cases, patients are serially monitored and advised to avoid contact sports or other activities that may place them at risk for catastrophic injury. Nonoperative management consists of treatment with a cervical collar, braces, or traction.

Notable risks of surgical treatment for AAI patients with concomitant CTDs include nonunion, infection, and death. Given the risk of surgical stabilization, the risks and benefits of surgery should be carefully discussed with the patient’s family and care providers.

Basilar Invagination

BI is another spinal disorder that can be present in the setting of a CTD. BI is an abnormality of the craniocervical junction caused by the upward displacement of vertebral elements (e.g., dens) into the foramen magnum, further limiting the space available for the brain stem and spinal cord. This phenomenon can either occur with normal bone at the base of the skull (BI) or with acquired softening of bones at the base of the skull (basilar impression). In general, the terms BI and basilar impression can be used interchangeably.

Osteogenesis imperfecta (OI) is a congenital disorder of type I collagen that is most frequently associated with BI. Patients with OI, particularly Sillence type III ( Table 51.1 ), present with characteristic bone fragility that manifests as softening of the bone at the base of the skull (basilar impression), allowing the upper cervical elements to migrate cephalad. Patients with BI can present with a wide range of signs and symptoms, such as cranial nerve palsies, dysmetria, nystagmus, and ataxia based on the anatomical structure compressed at the level of the foramen magnum. One pathognomonic sign is exertional headaches with cough, laughing, postural changes, or lifting weights.

Patients suspected of BI should be worked up with lateral cervical spine radiographs or MRI. Abnormal Chamberlain, McGregor, or McRae lines are deemed to be diagnostic for BI ( Fig. 51.2 ). The Chamberlain line starts at the posterior edge of the hard palate and ends on the opisthion. If the dens is greater than 3 mm above this line, this is diagnostic of BI. The McGregor line is a modification of the Chamberlain line that starts at the posterior edge of the hard palate and ends at the most caudal point of the occipital curve. If the tip of the dens lies greater than 4.5 mm above the McGregor line, this is diagnostic of BI. The McRae line is drawn from the basion to the opisthion, and it is diagnostic of BI if the tip of the dens crosses the McRae line. Normally, the tip of the dens is 5mm below the McRae line. Ranawat’s line, which is the distance between the center of the C2 pedicle and a line connecting the anterior and posterior C1 arches, can also be helpful in diagnosis.

Although there is no treatment consensus in the literature, patients who present with BI typically require procedural intervention. For pediatric OI patients, treatment can start with halo traction. Surgical intervention can be a posterior-only decompression and fusion or a combined anterior decompression and posterior stabilization approach. Treatment algorithm is predicated on whether or not the BI can be reduced. If it is reducible, halo traction and closed reduction with posterior stabilization is sufficient. Up to 82% of patients can experience rapid clinical improvement after treatment. Complete recovery, however, is not always attainable, with frequent reports of residual neurological deficits.

Cervical Failure of Segmentation

Patients with CTDs can also be predisposed to cervical failure of segmentation, which is part of the vertebral developmental process. There are six stages of vertebral embryological development: gastrulation, formation of somites, formation of dermomyotomes and sclerotomes, vertebral formation through membranous somites and resegmentation, vertebral chondrification, and ossification. Any disruption in the development of the vertebral column during gestation can lead to structural malformations, which can either be asymptomatic or have neurological manifestations. Patients with symptomatic malformations are at risk for spinal canal narrowing, myelopathy, and death.

Klippel–Feil syndrome is the pediatric disorder that best exemplifies defective vertebral segmentation. Patients with Klippel–Feil have partial or complete fusion of at least two adjacent cervical vertebrae and clinically present with a short neck, limited neck motion, and a low posterior hairline ( Fig. 51.3 ). In addition, they often have Sprengel deformity (in which one scapula is abnormally high), syringomyelia, tethered cord, Chiari malformation type I, and diastematomyelia. These characteristics, such as reduced neck mobility, increase the risk of trauma to the spinal cord with even minor injury, and make endotracheal intubation difficult.

Workup for patients with Klippel–Feil syndrome includes cervical AP, lateral, and odontoid radiographs, as well as cervical MRI. In addition, patients with Klippel–Feil are also predisposed to BI and AAI. Treatment for Klippel–Feil syndrome patients with cervical failure of segmentation depends on the level of fusion and the presenting symptoms. Asymptomatic patients with fusions below C3 are amenable to observation and participation in contact sports. However, asymptomatic patients with fusions at or above C2 are recommended to avoid sports with a high likelihood of collision. Surgical intervention is reserved for patients with concomitant BI, AAI, and myelopathic changes or chronic pain.