Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disease that commonly presents with polyarthropathy, systemic symptoms, and cervical spine involvement. Some reports state that RA was first described by A.J. Landre-Beauvais, whereas others credit Robert Adams. Robert Adams described it as a separate entity from gout in the nineteenth century in Dublin. The term rheumatoid arthritis was coined by A.B. Garrod, and its predilection for the cervical spine was first highlighted by his son, A.E. Garrod.¹

RA presents as a chronic disabling disease with intermittent flares and remissions. It reduces life expectancy, and half of all afflicted patients become disabled within 10 years of diagnosis. The cervical spine is the second most commonly affected site after the hands and feet. Cervical spine involvement is particularly concerning because of the neurological manifestations. Once the patient develops myelopathic symptoms, prognosis is poor.

The natural history can be modified by early and aggressive medical management. With the introduction of corticosteroids and DMARDs (disease-modifying antirheumatic drugs), people can be managed nonoperatively. However, once a patient starts developing myelopathic signs, surgical intervention becomes a consideration. Depending on each surgeon’s philosophy and the individual case, the timing of surgery may be controversial. However, studies show that patients with progressive myelopathy benefit from an early decompression and stabilization.

Patients with RA have a complicated presentation and require a multidisciplinary approach. Patients can often present with inability to grasp fine objects. This could be caused by cervical myelopathy, peripheral joint involvement in the hand and fingers, or both. Therefore, a treating physician must have a comprehensive understanding of the natural history, physical exam, radiologic findings, and treatment strategies associated with RA.

Epidemiology and Natural History

The prevalence of RA is up to 1% to 3% of the United States population. It is commonly seen in those 40 to 70 years of age, and the male to female ratio is approximately 1:3. Symptomatic cervical spine disease is present in 40% to 80% of patients with RA. Up to 86% of patients have radiographic evidence of cervical spine involvement. In a study that evaluated patients with RA undergoing hip and knee arthroplasty, over 60% had cervical spine involvement.²

Cervical subluxation can be identified in 15% of these patients within 3 years of being diagnosed with RA. Atlantoaxial subluxation develops in 5% to 73% of patients within 10 years of diagnosis. Subaxial subluxation develops in 20% of patients and can be at multiple levels. Neurological symptoms are found in 17% of patients. Of those who develop myelopathy, 50% die within 1 year if left untreated. In those left untreated, patients with atlantoaxial subluxation may progress to more complex instability patterns like cranial settling. The natural history of cranial settling is more aggressive with a poorer prognosis than that of isolated atlantoaxial instability. Ten percent of myelopathic patients with RA die a sudden death. It is thought that this is due to brain stem compression or vertebrobasilar insufficiency.

Predictors of disease progression and severity of cervical involvement include disease duration, rapid joint erosion, arthritis mutilans, history of high-dose corticosteroid use, high seropositivity, subcutaneous nodules, vasculitis, and male sex. Other postulated factors include elevated C-reactive protein and certain HLA positivities.

Pathophysiology

Rheumatoid arthritis is a chronic immune-mediated response. Unknown antigens, perhaps viral, trigger a cell-mediated response resulting in the release of various inflammatory mediators. The inflammatory response is put into motion by the CD4+ lymphocytes, which activate the B lymphocytes to produce immunoglobulins that are found in the rheumatoid synovium. The rheumatoid synovium contains two distinct cell types: type A cells are morphologically similar to macrophages and type B cells are similar to fibroblasts. Type A cells are mainly for phagocytosis, whereas type B cells are highly metabolic and are equipped with organelles for protein synthesis. These cells produce multiple inflammatory mediators, such as TNF-α, metalloproteinases, collagenases, progelatinases, and IL-1.³ These mediators are targets for DMARDs.

This inflammatory reaction has an affinity for synovial joints. In the cervical spine, these joints include the atlantooccipital, atlantoaxial, facets, and uncovertebral joints. The atlantooccipital and atlantoaxial articulations are the only two segments in the spine without intervertebral discs, which may account for the great tendency for instability at these regions. Once this inflammation, pannus formation, and ligamentous and bony erosions occur, progressive cervical instability ensues. It is seen in the cervical spine, in order of frequency, as atlantoaxial subluxation, subaxial subluxation, and cranial settling.

Atlantoaxial instability is the most commonly seen (40% to 70%) affliction in the rheumatoid spine. The formation of periodontoid pannus leads to erosion of the transverse, alar, and apical ligaments. The weight of the head combined with flexion and extension at this level leads to stretching and eventual rupture of these ligaments. The odontoid itself and the lateral atlantoaxial articulations are commonly eroded as well, leading to further instability. Depending on the pattern and location of bony and ligamentous erosion, the subluxation may present as anterior, posterior, lateral, or rotational. Anterior is the most common (70%). Anterior subluxation of 0 to 3 mm is normal in adults, 3 to 6 mm is suggestive of instability and rupture of the transverse ligaments, and greater than 9 mm suggests gross instability and incompetence of all periodontoid stabilizing structures. Posterior subluxation is rare and may be associated with a defect in the anterior C1 arch or fracture or erosion of the odontoid. Lateral subluxation is defined as 2 mm of lateral displacement at the atlantoaxial articulation.

Subaxial subluxation is the second most common (20% to 25%) manifestation in the cervical spine. Erosions of the facet joints, uncovertebral joints, and interspinous ligaments result in anterior subluxation of the subaxial vertebrae. It is most commonly seen at the C2-3 and C3-4 levels and typically affects multiple levels resulting in a “staircase” deformity. Subaxial subluxation also occurs at adjacent levels after an atlantoaxial fusion.

Cranial settling, or basilar invagination, is a late finding that is due not only to ligamentous and capsular erosion, but mainly to bone and cartilage destruction of the atlantoaxial and atlantooccipital articulations (Figure 31-1). Cranial settling carries an ominous prognosis. Anterior compression of the medulla oblongata can lead to injury to cranial nerve nuclei, syringomyelia, or obstructive hydrocephalus. Sudden death may also occur due to brainstem compression or vertebrobasilar dysfunction.

FIGURE 31-1 Lateral view of the upper cervical spine, demonstrating basilar invagination (arrow) of the odontoid process into the foramen magnum. Note the compression of the spinal cord.

(Reproduced with permission from Boden SD, Dodge LD, Bohlman HH, Rechtine GR: 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.)

Clinical Presentation

Patients with RA present with general symptoms specific to RA as well as symptoms due to spinal involvement. General symptoms include fatigue, weight loss, malaise, morning stiffness, and anorexia. Rheumatoid arthritis of the cervical spine may often be asymptomatic. Neck pain, however, is the most common symptom (40% to 80%). Patients often have facial, temporal, and occipital pain due to irritation of the C1-2 nerve roots, trigeminal nerve, greater auricular nerve, and greater occipital nerve. Occasionally, patients may complain of a “clunking” sensation on flexion and extension corresponding to subluxation and reduction at the C1-2 level (positive Sharp-Purser test).

Objective neurological signs occur in 7% to 34% of patients. Patients may present with simple radiculopathy or more complex myelopathy. Radiculopathy may manifest as paresthesias, numbness, or weakness in specific nerve root distributions. Myelopathic signs are seen, and significant spinal cord compression occurs. Clinical signs and symptoms include a wide-based spastic gait, clumsy hands (difficulty grasping coins or buttoning one’s shirt), and change in handwriting. Loss of bowel and bladder function occurs late. Compression of the pyramidal tract may occur, leading to a “cruciate paralysis” with varying degrees of upper extremity weakness.

Physical examination reveals general signs of RA and those specific to cervical spine involvement. The general exam reveals peripheral joint involvement characterized by stiffness, redness, warmth, and bogginess. Some patients may have nodules over the extensor surfaces of joints (typically elbows); this occurs in 20% of patients. On exam of the cervical spine, the patient may present with torticollis, lateral head tilt, tenderness to palpation, and painful, restricted range of motion. Neurological abnormalities are seen in 7% to 10%. Patients may present with weakness or paresthesias. Myelopathic findings include hyperreflexia, hypertonia, clonus, positive Babinski test, and positive Hoffman sign.

Careful examination is necessary, as neurological deficit can be masked by weakness from peripheral joint involvement. Myelopathy is progressive and often goes unnoticed because of peripheral involvement. Fine motor skill deterioration may be mistaken for hand involvement, or decreasing ambulatory status may be mistaken for large joint involvement. As patients become more myelopathic, prognosis worsens. The Ranawat grading system for neural assessment may be used to appropriately classify the severity of myelopathy and can be used as a prognostic tool (Table 31-1).

TABLE 31-1 Ranawat Grading Scale for Myelopathy

Laboratory Data

Abnormal laboratory findings include anemia, elevated erythrocyte sedimentation rate, and an increase in serum globulin level. Thrombocytosis may also be seen in patients with active disease. Rheumatoid factors (antibodies directed at other host antibodies) are present in 80% of patients. Antinuclear antibodies may be present in 30% of patients. Potential risk factors for cervical involvement include elevated C-reactive protein and HLA-Dw2 or HLA-B27 positivity.

Radiographic Analysis