Historical Perspective

There is some evidence that rheumatoid arthritis was described in the 17th and 18th centuries.^6,7 More concrete evidence points to a period around 1800, according to a description by Landré-Beauvais, a French medical student, in his doctoral thesis.⁸ The description of rheumatoid arthritis of the cervical spine occurred much later, with a report in 1890 by Garrod.⁹

Interest increased in the 1950s and 1960s with reports describing cervical instability.^10–13 Articles on the surgical treatment of cervical instability in patients with rheumatoid arthritis followed in the 1960s and 1970s.^14–18 For the most part, C1-2 fusion with Gallie-type¹⁹ wiring and graft techniques were used early on. Brooks and Jenkins,²⁰ Wertheim and Bohlman,²¹ and Clark and colleagues²² subsequently described modified wiring techniques. Other types of C1-2 fixation emerged later with the use of the Halifax interlaminar clamp,²³ the Magerl transarticular screw technique,^24–28 and posterior C1 lateral mass–C2 pedicle screw fixation.²⁹

Foerster³⁰ originally described occipitocervical procedures in 1927. Kahn and Yglesias³¹ were the first to add iliac crest bone graft to occipitocervical fusion in 1935. Hamblen¹⁶ later described the combined use of wires and iliac crest graft for occipitocervical fusion in four patients with rheumatoid arthritis and cervical instability in 1967. In a 1976 report, Brattström and Granholm¹⁴ modified the wiring technique for occipitocervical fusion by adding methyl methacrylate. Modifications of occipitocervical fusion techniques continued in the 1980s with the emergence of the looped rod with iliac crest bone graft, as described by Ransford ³² and Flint ³³ and their colleagues and later occipitocervical plating, as described by Grob^34,35 and Smith³⁶ and their colleagues. Current use of plate or rod fixation extends to the subaxial spine, especially with fixation of the lateral masses described by Magerl and Roy-Camille.^25–27

Pathophysiology

The inflammatory process in the cervical spine mirrors the inflammatory process in other sites of the body and consists predominantly of T lymphocytes, macrophages, and plasma cells in a hypervascular synoviocyte pannus.^37,38 The inflammatory reaction has a predilection for synovial joints, and the multiple synovial joints³⁹ of the cervical spine (facets, uncovertebral, atlanto-occipital, atlantodens) are particularly affected. In contrast to the thoracic and lumbar spine, the cervical spine relies heavily on ligaments and joint congruency for stability and so is at greater risk for instability. With significant inflammation, pannus formation and erosion of the joint and capsular structures can occur. Progressive instability can result, manifesting as atlantoaxial (C1-2) instability, subaxial subluxation, cranial settling (also known as basilar invagination or atlantoaxial impaction), or a combination thereof. Rheumatoid discitis may also occur at the discovertebral junctions with noninfectious erosion of the endplates.³

Atlantoaxial instability is the most common instability pattern in the rheumatoid cervical spine and may be the result of the development of periodontoid pannus and progressive inflammatory destruction of the upper cervical spine.^39–41 Pannus formation localizes around the synovial joint formed between the transverse ligament, the posterior arch of the atlas, and the base of the odontoid. The soft tissue may compress the spinal cord and often distends and erodes the surrounding periodontoid-ligamentous structures (alar, apical, and transverse ligaments), the odontoid process (dens), and the lateral articular masses between C1 and C2.⁴² Erosion of the dens may lead to the development of occult, atraumatic odontoid fractures.⁴³ Subsequent static or dynamic instability or subluxation occurs in 50% to 70% of patients.^18,44 Most often, the subluxation is anterior (70%), but lateral, posterior, and rotational subluxations can also occur.^45,46 Anterior subluxation of 0 to 3 mm is normal in adults, subluxation of 3 to 6 mm suggests instability with disruption of the transverse ligament, and subluxation of 9 mm or more suggests disruption of the entire periodontoid-ligamentous and capsular structures with gross instability and is a clear indication for surgery.^18,47,48

The combination of periodontoid pannus buildup and instability may cause spinal cord and root impingement leading to myeloradiculopathy and sudden death. Delamarter and Bohlman⁴⁹ conducted postmortem studies suggesting that paralysis can be due to mechanical neural compression, vascular impairment of the neural structures, or both. Henderson and colleagues⁵⁰ reported that diffuse axonal injury with or without frank necrosis may irreversibly affect the spinal cord owing to mechanical damage. These findings may partly explain the smaller diameter and cross-sectional area of the spinal cord found in patients with severe disease.⁵¹ Some evidence suggests that instability promotes worsening periodontoid pannus formation and that stabilization reverses the buildup.⁴⁰

Posterior atlantoaxial subluxation is rare and should raise the possibility of an anterior arch defect of the atlas or erosion or fracture of the odontoid.⁴⁸ Patients usually present with myelopathy and posterior kinking of the cord without radiographic compression.⁵² Lateral subluxation is defined as more than 2 mm of lateral displacement of the C1-2 lateral masses and occurs in 21% of atlantoaxial subluxations.⁴⁸ Lateral subluxations occur more commonly in patients with spinal cord compression than patients without compression and are often accompanied by rotational subluxation.⁵³

Subaxial subluxation is the second most common instability pattern and results from destruction of the facet joints, interspinous ligaments, and discovertebral joints.^44,54 These pathologic changes can lead to longitudinal collapse, bony erosion, soft tissue hypertrophy, and sagittal plane instability along multiple spinal segments, causing a “stepladder”-type pattern of deformity. Concurrent spondylodiscitis may occur with pain, neural compression, and instability.

Cranial settling occurs primarily because of bone and cartilage destruction of the atlantoaxial and occipitoatlantal joints in contrast to ligamentous laxity. Although the least common of the three instability patterns, it is the most ominous form. Caudad settling of the cranium and apparent cranial migration of the odontoid are characteristic. As a result, there is an increased risk of sudden death from either static or dynamic stenosis of the foramen magnum and compression of the medulla oblongata (brainstem). Other sequelae include obstructive hydrocephalus or syringomyelia presumably from direct mechanical blockage of normal cerebrospinal fluid flow. In some cases, fixed rotation of the head may occur because of unilateral involvement of the atlantoaxial and occipitoatlantal joints.

Natural History

It is difficult to study the natural history of rheumatoid arthritis because patients are usually treated at some stage of the disease and it would be unethical to do otherwise. From studies on rheumatoid arthritis, it seems consistent that the inflammatory processes in the cervical spine begin early after the onset of rheumatoid arthritis and progress along with peripheral involvement. Atlantoaxial instability may be detected within 2 to 10 years of disease onset in most patients,⁵⁵ and there is a strong correlation between cervical spine subluxation and peripheral erosions of the hands and feet.⁵⁶ Approximately 10% of patients with cervical spine involvement eventually require surgery.⁵⁷

The natural history of rheumatoid arthritis of the spine without surgical intervention, especially in patients with myelopathy, seems to be progressive disability and risk of sudden death. In one study of 21 patients treated medically, 76% showed deterioration at an average of 6 years of follow-up. All patients in the study became bedridden within 3 years of developing myelopathy, and all died within 7 years with one third dying suddenly for unknown reasons.⁵⁸ Risk factors for progression include mutilating articular disease, history of high-dose corticosteroid use, high seropositivity, rheumatoid subcutaneous nodules, vasculitis, and male gender. Other potential but unproven risk factors for cervical involvement include high C-reactive protein level and HLA-Dw2 or HLA-B27 positivity.^59,60 As the disease progresses, pain, neurologic deficits, and sudden death are the primary risks.

Clinical Presentation

Neck pain is the most common symptom in patients with cervical spine involvement. Peripheral erosive changes similarly occur along the apophyseal joints and surrounding soft tissues and may be a source of pain. Cervical instability may cause secondary impingement of the posterior rami of the lesser and greater occipital nerves, which may lead to occipital headaches. Pain in the suboccipital region generally suggests atlantoaxial pathology or cranial settling. Middle or lower cervical pain should suggest subaxial subluxation. These are not hard and fast rules because pain localization in rheumatoid cervical disease may be poor. Subaxial involvement may also lead to painful neck deformity with loss of sagittal plane supporting structures, which may later become fixed deformities owing to postinflammatory ankylosis. Patients may complain of a “clunking” sensation in the neck with neck motion. This sensation is most common in patients with C1-2 instability, owing to spontaneous reduction of the subluxation with neck extension (known as the Sharp-Purser test).⁶¹

Progressive instability leads to decreased effective canal diameter and brainstem compression. Myelopathy and vertebrobasilar dysfunction may result because of mechanical and ischemic damage to the white and gray matter evidenced on histologic specimens by long tract demyelinization, lateral column necrosis, and focal gliosis.⁴⁹ According to Bell,⁶² C1-2 instability may lead to a phenomenon termed cruciate paralysis, characterized by upper motor neuron dysfunction of the upper extremities with paresis and paralysis and normal lower extremities similar to a mild central cord syndrome after trauma. Pathologically, there is selective injury to the decussating corticospinal tracts of the upper extremities at the level of the cervicomedullary junction with sparing of the uncrossed lower extremity pyramidal and extrapyramidal tracts.

Additional neurovascular changes may occur because of vertebral artery occlusion with decreased flow into the posterior inferior cerebellar artery and cephalad brainstem circulation. Without adequate collateral blood flow, these patients may develop Wallenberg syndrome or lateral medullary infarction. These clinical syndromes are characterized by ipsilateral cranial nerve palsies (cranial nerves V, IX, X, and XI), cerebellar ataxia, Horner syndrome (ptosis, miosis, anhidrosis, and enophthalmos), facial pain, and contralateral loss of pain and temperature sensation.⁶³ Rarely, patients may develop quadriplegia, quadriplegia with facial muscle paralysis (locked-in syndrome),⁶⁴ and sudden death.^38,58

In contrast to pain symptoms, neurologic signs are less straightforward. Myelopathy is progressive but may not be evident by loss of fine motor control, gait imbalance, or global numbness of the hands, but rather by the slow onset of deteriorating independence and becoming wheelchair bound. In many instances, hand deformities mask motor deficits in the upper extremities, and the patients’ deteriorating ambulatory status may be attributed to large joint involvement rather than myelopathy. Patients must be assessed keeping their global disease in mind. Progression of myelopathy, especially early disease, may be misinterpreted as progression of peripheral disease. A high index of suspicion is necessary in these patients to detect early myelopathy because patients do poorly without early surgical intervention.^38,58

The Ranawat grading system may provide some useful clinical information in assessing patients with neurologic deficits (Table 34–1).⁶⁵ This system classifies pain as none (grade 0), mild (1), moderate (2), or severe (3). Neurologic function falls into three classes: Class I has no neurologic deficit; class II has subjective weakness, dysesthesia, and hyperreflexia; and class III has objective weakness and long tract signs. This last class is subdivided further into class IIIA, in which patients are ambulatory, and class IIIB, in which patients have quadriparesis and are unable to walk. Casey and colleagues⁶⁶ reported that only 25% of 55 Ranawat class IIIB patients who underwent surgical decompression and stabilization had a favorable outcome. The mortality rate was 13% after 30 days and 60% by 4 years.

TABLE 34–1 Ranawat Criteria for Pain and Neural Assessment

Adapted from Ranawat CS, O’Leary P, Pellici P, et al: Cervical spine fusion in rheumatoid arthritis. J Bone Joint Surg Am 61:1003-1010, 1979.

Radiologic Evaluation

Plain radiographs are an effective screening tool for identifying patients with atlantoaxial instability, cranial settling, or subaxial subluxations. Standard anteroposterior, open-mouth (odontoid view), lateral, and controlled flexion-extension plain views should suffice. The flexion-extension views are the most important in detecting whether there is dynamic or static instability in the upper or lower cervical spine and allow for measurement of the anterior atlantodental interval (AADI) and posterior atlantodental interval (PADI). AADI is measured from the anterior surface of the dens to the posterior margin of the anterior ring of the atlas along a transverse axis of the atlas, whereas PADI is the distance between the posterior surface of the dens and the anterior margin of the posterior ring of the atlas.

Historically, the AADI was used to screen patients who required surgical stabilization for atlantoaxial instability based on an AADI greater than 9 mm, with AADI 0 to 6 mm suggesting instability and AADI 0 to 3 mm being normal.⁴⁸ AADI is limited by the occasional difficulty of obtaining accurate measurements in some patients because of erosive changes that distort the normal anatomic landmarks and because it has not been correlated clinically with the mass effect of retrodental pannus that may compress the spinal cord. Boden and colleagues⁶⁷ showed that PADI may be more reliable in predicting neurologic outcome because it is a more accurate indicator of the space available for the cord. Patients with a PADI of at least 14 mm were more likely to have neurologic recovery after surgical stabilization, whereas patients with a PADI less than 10 mm had no neurologic recovery. These observations can also be explained by the anatomy of the spinal cord at the C1 level because the dura requires an average space of 1 mm on the anterior and posterior sides, the cerebrospinal fluid requires 2 mm, and the cord requires 10 mm for a total space of 14 mm.⁶⁸

The open-mouth view is useful to identify lateral subluxation, defined as more than 2 mm of lateral displacement of C1-2 lateral masses, which occurs more commonly in patients with spinal cord compression than in patients without compression.^48,53 Erosive changes of the dens and C1-2 articulations may also be visualized. Taniguchi and colleagues⁶⁹ defined the atlantodental lateral shift (ADLS) as a means of assessing lateral atlantoaxial instability. Using dynamic open-mouth odontoid views (taken in maximal left and right lateral bending), ADLS is calculated by dividing the distance from the center of the dens to the medial edge of the C1 lateral mass (in the direction of lateral bending) by the distance between the medial borders of the bilateral C1 lateral masses and is expressed as a percentage. With this method, these investigators noted that in patients with rheumatoid arthritis, the ADLS averaged 14.8% compared with 6.1% in control patients. Among the subgroup of patients with rheumatoid arthritis and increased AADI, the ADLS averaged 20.6% versus 12.7% in patients without anterior atlantoaxial instability.

Posterior subluxation, although rare, may be seen on lateral radiographs of the cervical spine and should be suspected in patients with an absent or fractured odontoid process.⁵² The AADI decreases with worsening cranial settling as the arch of the atlas approaches the wider base of the odontoid process and is a potential source of mistaken radiographic improvement.

Cranial settling carries the greatest risk of neurologic deficits and sudden death, especially when superimposed on atlantoaxial instability. As a consequence, several measurement techniques have been used with varying sensitivity and specificity, based on lateral plain radiographs of the upper cervical spine (Fig. 34–1).⁷⁰ Most of these techniques assess the relationship between the tip of the odontoid, the hard palate, and the base of the skull. Traditionally, McGregor line (drawn from the posterosuperior tip of the hard palate to the caudad base of the occiput) has been widely used for its simplicity. Cranial settling occurs when the tip of the dens is more than 4.5 mm above this line.

FIGURE 34–1 Drawing of lines for measurements of basilar invagination. Chamberlain line: Odontoid tip greater than 6 mm above line. McCrae line: Odontoid tip above this line. McGregor line: Men, odontoid tip greater than 8 mm above line; women, odontoid tip greater than 9.7 mm above line. Redlund-Johnell distance: Men, less than 34 mm; women, less than 29 mm.

Erosive changes in the odontoid anatomy may make it difficult to analyze many of the measurement techniques, so Redlund-Johnell and Pettersson⁷¹ described a technique that measured the vertical line from the midpoint of the caudad margin of C2 to McGregor line. Cranial settling occurs when the distance is less than 34 mm in men or less than 29 mm in women. Ranawat and colleagues⁶⁵ described a similar technique in which the distance along the odontoid was measured from the C2 pedicle to the transverse axis of the ring of C1. This technique avoided problems with changes in odontoid anatomy and identifying the bony landmarks at the base of the skull and hard palate. Cranial settling was positive if the distance was less than 15 mm in men or less than 13 mm in women. Clark and colleagues²² defined the “station of the atlas” (Fig. 34–2), which indicates the position of the anterior ring of C1 to parts of the body of the axis divided into thirds. Normally, the atlas is adjacent to the upper third (station I) of the axis. Riew and colleagues⁷⁰ noted that none of the current radiographic measurements alone had a sensitivity, specificity, or negative or positive predictive value greater than 90% and recommended the combination of the Clark station, Redlund-Johnell criteria, and Ranawat criteria with sensitivity and negative predictive values of 94% and 91%.

FIGURE 34–2 Station of atlas is determined by dividing odontoid process into thirds in sagittal plane. Normally, anterior ring of atlas should be adjacent to cephalad third of axis (station I). If ring of atlas is adjacent to middle third of axis, mild cranial settling is indicated (station II). If anterior ring of atlas is adjacent to base of axis, it is considered evidence of severe cranial settling (station III).

(From Clark CR, Goetz DD, Menezes AH: Arthrodesis of the cervical spine in rheumatoid arthritis. J Bone Joint Surg Am 71:381-392, 1989.)

Subaxial subluxation is the second most common instability pattern and occurs secondary to inflammatory destruction of the apophyseal and discovertebral joints and supporting soft tissues. White and Panjabi⁷² defined radiographic cervical instability as 3.5 mm or more of vertebral translation and greater than 11 degrees of angular changes between adjacent motion segments, although their study is more representative of acute conditions. The space available for the cord should also be considered in these patients because critical stenosis may be present with or without instability. Boden and colleagues⁶⁷ correlated anatomic measurements with neurologic findings and reported that a sagittal diameter of less than 14 mm was considered critically stenotic in the rheumatoid subaxial spine. This is in contrast to 13 mm in cervical spondylotic patients who do not have pannus in the canal.

Computed tomography (CT), especially with intrathecal contrast medium, is a valuable addition to plain radiographs in delineating the bony anatomy and identifying cord compression and cranial settling. The degree of medullary compression on CT scans has been shown to correlate with myelopathy.⁴⁰ Static or dynamic magnetic resonance imaging (MRI) is the best option, however, to assess the soft tissues and to look for the presence of periodontoid pannus (Fig. 34–3) and spinal cord or brainstem compression.^73–75 MRI is also useful for postoperative evaluation of the periodontoid pannus, which has been shown to decrease after stabilization.⁴⁰ Myelopathic signs correlate with MRI findings⁷⁵ of a cervicomedullary angle of less than 135 degrees (normal 135 to 175 degrees). This angle measures the intersection of vertical lines drawn along the anterior surface of the brainstem and the cord on sagittal MRI.

FIGURE 34–3 Illustration showing forward subluxation of atlas on axis, pannus formation around odontoid process, and osseous erosions. There is severe compression of spinal cord between pannus anteriorly and arch of atlas posteriorly.

(From Boden SD, Dodge LD, Bohlman HH, et al: Rheumatoid arthritis of the cervical spine: A long term analysis with predictors of paralysis and recovery. J Bone Joint Surg Am 75:1282-1297, 1993.)

Nonsurgical Treatment

Although life expectancy is lower in patients with rheumatoid arthritis, many are living longer with their disease because of more aggressive medical therapy that has slowed disease progression with fewer side effects.⁵⁹ Only a few of these patients eventually need surgical stabilization. Patients with early cervical disease and intermittent pain without radiographic instability or myelopathy can be managed with a soft cervical orthosis or trials of physical therapy. Medication options include nonsteroidal anti-inflammatory drugs (NSAIDs); oral steroids (prednisone); and disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, gold, sulfasalazine, hydroxychloroquine, penicillamine, and azathioprine.

In recent years, biologic agents such as tumor necrosis factor (TNF)-α and interleukin-1 antagonists have become increasingly available. The addition of antiresorptive osteopo-rosis therapy may improve vertebral bone strength in patients with rheumatoid arthritis.⁷⁶ Patients should be followed closely for neurologic or radiographic changes. Cervical collars provide support, warmth, some pain relief, and a feeling of stability; however, rigid collars are often poorly tolerated, especially in patients with temporomandibular disease, dental problems, and skin sensitivity, and may have further detrimental effects by blocking spontaneous reduction of anterior atlantoaxial subluxation in extension.

Surgical Management