Immunologic Features

Rheumatoid factors are antibodies with specificity for the Fe fragment of immunoglobulin G (IgG).^17,18 The latex agglutination test is positive in 80% of patients meeting the American Rheumatism Association criteria (Table 289-1).¹⁹ High titers are associated with the presence of subcutaneous nodules, extra-articular manifestations, and vasculitis. A negative rheumatoid factor test by routine laboratory procedures does not exclude the diagnosis of RA because 20% of patients who meet the American Rheumatism Association criteria test negative for RA. These patients may have IgG or IgM rheumatoid factor that is not detectable by routine techniques.²⁰

TABLE 289-1 American Rheumatism Association Criteria for Classic or Definite Rheumatoid Arthritis

Antinuclear antibodies have been found in 14% to 28% of patients with RA. Tests that use monoclonal rheumatoid factors in the CLq binding assay are more frequently positive in patients with RA than all the various assays for the detection of immune complexes.¹⁵ Although the assays correlate poorly with indices of disease activity, a positive test is usually associated with an increased incidence of extra-articular manifestations, particularly vasculitis.

More recently, anti–cyclic citrullinated peptide (anti-CCP) antibodies have been identified in patients with RA. These antibodies react to a variety of citrullinated proteins, including filaggrin and keratin. These antibodies have been identified in the serum of patients before the onset of RA symptoms, suggesting that they play a role in the pathogenesis of the disease. Anti-CCP antibodies have a greater specificity for RA than does rheumatoid factor. Taken together, positivity for rheumatoid factor and anti-CCP antibodies is 98% specific for RA.²¹

The cause of RA is unknown. However, it is postulated that the disease is triggered by an infectious agent. Macrophages present this antigen on their surface, inciting the release of cytokines such as tumor necrosis factor (TNF) and initiating the inflammatory cascade. This macrophage activation is dependent on human leukocyte antigen (HLA) molecules, explaining the predisposition for RA in patients with particular HLA haplotypes (HLA-DR4 and HLA-DR1). In addition to macrophages, T cells (predominantly Th1 cells), B cells, plasma cells, natural killer cells, dendritic cells, and mast cells infiltrate the synovium, transforming it into the rheumatoid pannus. T cells interact with B cells, which subsequently secrete autoantibodies that further promote the inflammatory response through the recruitment and activation of complement and neutrophils. In addition, synovial fibroblasts respond, developing into RA synovial fibroblasts, which play an active role in joint destruction. RA synovial fibroblasts, macrophages, and T cells secrete a number of chemokines, including interleukin-1β, interleukin-17, and TNF, which promote the production of matrix metalloproteinases. Other molecules such as cathepsins, collagenases, and stromelysin are secreted and participate in the destructive processes. In addition, the cytokine milieu results in the activation of osteoclasts.^22–24

Rheumatoid pannus forms in the inflamed joints from proliferating fibroblasts and inflammatory cells, leading to granulation tissue.²⁵ The pannus itself produces collagenase and proteolytic enzymes capable of destroying adjacent cartilage, tendons, and bones.²⁶ In addition, some patients develop lymphoid germinal centers within the synovium consisting of follicular aggregates of T cells, B cells, and dendritic cells.²¹ The end result is loss of cartilage, ligamentous laxity, rupture of tendons, and bone erosion. In general, the joints ultimately undergo severe destruction and become symptomatic within the first year of disease onset.

Clinical manifestations of RA include constitutional symptoms; arthritis involving large, medium, and small joints, and extra-articular manifestations that include subcutaneous nodules, nail bed thrombi, pleurisy, pulmonary fibrosis, pericarditis, nerve entrapment syndromes, scleritis, and vasculitis. The most common vascular complications are peripheral cutaneous ulcers and neuropathy.^27–31

The earliest changes in the cervical spine most likely take place at the superficial joints and the lateral margins of the disks. Neurocentral synovitis results in granulation tissue with fibroblasts and capillaries that erode and replace the disk annulus and neighboring disk-bone border. This is not accompanied by active bone formation.³² Therefore, osteophyte formation around disks and apophyseal joints is inconspicuous, enhancing the possibility of dislocation.^13,33,34

Fibrosis and ankylosis of apophyseal joints are not uncommon in untreated cases, and there is a natural tendency for the disease to terminate in segmental immobilization, with loss of disk and stepwise subluxation in the subaxial cervical region. The active inflammatory lesions with fibrinoid changes are similar to those in the tendons of the hand and are thus seen in the apical ligaments, the transverse ligament of the craniocervical junction, and biopsy specimens of the interspinous ligaments.³⁵ The transverse ligament becomes insufficient because of inflammatory erosion of the posterior surface of the odontoid process by granulation tissue arising in the synovial joints between the transverse ligament and the posterior surface of the odontoid process. Osteoporosis is a frequent finding in the rheumatoid cervical spine and may contribute to weakening of the bone beneath the ligamentous attachments.^35,36

Rheumatoid Involvement of the Spine

The cervical spine is the most common site affected because of the large number of synovial joints. There is a predilection for involvement of the craniocervical junction for this reason. The most common lesion found is atlantoaxial dislocation, followed by cranial settling and then rheumatoid granulation tissue. Subaxial subluxation occurs in 12% to 22% of individuals and is seen predominantly at the C4 and C5 levels.³⁷ Winfield and colleague³⁸ evaluated 100 rheumatoid patients diagnosed within 1 year of the onset of disease. At 5-year follow-up they found that 12 patients had atlantoaxial subluxation of more than 7 mm, and subaxial subluxation had occurred in 20. In 3 individuals, vertical migration of the odontoid process had occurred. Zikou and coworkers³⁹ reported a series of 165 consecutive patients with RA, 66 of whom reported symptoms of cervical spine involvement, including neck pain, neck stiffness, and limited cervical range of motion. Interestingly, 146 of 165 patients had radiographic evidence of rheumatoid disease of the cervical spine, including 80 patients who had no symptoms referable to the cervical spine. The radiographic findings included atlantoaxial subluxation greater than 2.5 mm (20.6%), subaxial subluxation greater than 1 mm (43.6%), and odontoid erosions (2.4%). This same group reported on a series of 51 patients with RA who underwent magnetic resonance imaging (MRI) investigation of the cervical spine. Thirty of these patients had clinical evidence of cervical spine disease, and 40 had other radiographic evidence of cervical spine involvement. On MRI, 88% of the patients demonstrated some degree of pannus formation at the dens, 23.5% had dens erosion, 13.7% had atlantoaxial subluxation, and 10% had subaxial subluxation.⁴⁰ In longitudinal studies, it appears that atlantoaxial subluxation begins with horizontal subluxation, progresses to a combination of vertical and horizontal subluxation, and ultimately develops into vertical subluxation alone in a subset of patients. It is rare for patients to develop vertical subluxation alone without first passing through a stage of horizontal subluxation. More severe atlantoaxial subluxation was observed in patients with more severe systemic disease.⁴¹

Atlantoaxial subluxation is initiated by a loss of tensile strength and stretching of the transverse ligament. Similar changes occur in the synovial joints around the odontoid process as in the joints of the lateral atlantoaxial and occipitoatlantal regions. Thus, there are erosive changes in the adjacent bone, formation of granulation tissue in the synovial joints, loss of bone volume, osteoporosis, angulation of the softened bone, and occasionally fracture. The laxity of the ligaments, together with the bone changes, leads to horizontal or anteroposterior translation as well as rotary luxation of the atlas and the axis vertebrae (Fig. 289-1).^42–49

FIGURE 289-1 Preoperative (A) and postoperative (B) cervical spine radiographs in a 68-year-old individual with Felty’s syndrome. Preoperative atlantoaxial dislocation is evident. This was easily reduced with cervical traction and maintained with interlaminar fusion.

Vertical penetration of the odontoid process into the foramen magnum has been variably termed rheumatoid basilar invagination, odontoid vertical migration, rheumatoid translation, and cranial settling.^9,13 It is caused by the loss of bone and the lateral mass of the atlas vertebra, with rostral migration of the axis. The lateral atlantal masses may fracture in severe cases with lateral displacement.²⁵ The odontoid then penetrates further through the foramen magnum. The destructive changes may be severe enough that the occipital condyles rest on the lateral masses of the axis vertebrae, separating and displacing the anterior and posterior arches of the atlas and their respective directions (Fig. 289-2).⁵⁰ The anterior arch of the atlas settles downward, telescoping onto the axis body, and there is an upward invagination of the odontoid process. This is not basilar invagination or basilar impression but cranial settling.^{9,25,28,51–53} Casey and colleagues⁵⁴ reported on a prospective review of 256 patients with RA. Of the 186 patients with cervical myelopathy, 62% had cranial settling (vertical translocation). The patients with cranial settling had more severe neurological dysfunction than those with horizontal subluxation. In addition, patients with cranial settling experienced pseudostabilization, with a decrease in the atlantodental interval and a resulting decrease in the size of the pannus.

FIGURE 289-2 A, Midline polytomogram of craniocervical junction and line drawing illustrating the odontoid process penetrating the posterior fossa. The anterior atlas arch is at the C2-3 disk interspace. B, Frontal tomogram through the plane of the odontoid process in a patient with cranial settling. The lateral atlantal masses are widely separated. The occipital condyles appear to rest on the slopes of the axis.

Excessive proliferation of granulation tissue may lead to complete destruction of the odontoid process, with the granulation mass and pannus emanating out of the rest of the synovial joints.³¹ This causes ventral and lateral cervicomedullary compression with gross dislocation in all directions (Fig. 289-3). At times the bony spicule of the odontoid process may be left as a ghost and can penetrate the tectorial membrane, subsequently embed in the ventral aspect of the pons and the medulla, and attach itself to the vertebrobasilar arterial tree. Occasionally, rheumatoid dural nodules and pachymeningitis occur secondary to the rheumatoid process. The rheumatoid pannus may be associated with granulation tissue and become tough and fibrotic.³¹ This does not usually recede with immobilization. In contrast, active pannus that resembles the active disease in other joints recedes with cervical immobilization.^53,55–57

FIGURE 289-3 Midline sagittal polytomogram with iohexol contrast outlining the subarachnoid space and spinal cord. The odontoid process is atrophic. There is a large ventral mass behind the axis body and the odontoid process, representing tough pannus, and marked compression of the ventral cervicomedullary junction. This patient underwent ventral decompression and dorsal occipitocervical fusion.

Subluxation below the second cervical vertebra occurs in 17% to 29% of patients with RA, most commonly at the C3-4 and C4-5 levels. Serial cervical subluxations producing a staircase appearance are common.^12,58

The natural history of rheumatoid disease of the cervical spine is grim. Fujiwara and associates⁴¹ reported on a series of 173 patients with RA followed from 1992 to 1997. Initially, 29% of the patients had atlantoaxial subluxation. Over the 5-year period, 63% of these patients experienced progression of their atlantoaxial disease. In addition, 39% of the patients who initially had no atlantoaxial subluxation developed upper cervical spine disease over the course of the study. At the beginning of the study period, no patients had neurological deficits; by the end of the study, 10 patients were myelopathic. Pellicci and coworkers⁵⁹ studied RA patients over a 5-year period and found a mortality rate of 17%, as opposed to a 9% mortality rate for the same age group without rheumatoid disease. Subluxation worsened in 80%, and new subluxation occurred in 27%. Mikulowski and associates⁶⁰ reported on a postmortem study of 104 patients with RA and found the cause of death in 11 patients to be atlantoaxial dislocation with cervicomedullary compression. This had not been suspected antemortem. Two patients had myelomalacia, and three others had cervical vertebral artery vascular complications related to dislocation. In 1981 Marks and Sharp³³ reported on 31 patients with RA and upper cervical spine involvement with dislocation. Fifteen deaths occurred within 6 months of presentation. All those who were untreated died, as did 50% of those treated with a soft cervical collar alone. Only fusion provided a reasonable chance of survival. Delamarter and Bohlman³ performed a postmortem analysis of patients with paralysis secondary to RA of the cervical spine and found cervical cord compression to be the main cause of death in 10. Thus, once cervical myelopathy sets in, the natural history is grave unless surgical intervention takes place.^31,61–63

Autopsy analyses of spinal cords from rheumatoid patients suffering from paralysis secondary to atlantoaxial dislocation or cranial settling have shown abnormal histology within the spinal cord at the site of compression.³ Common to all patients were gliosis and axonal degeneration, with nuclear damage within the ganglion cells frequently appearing in different stages of progression. No parenchymal hemorrhage was seen. Delamarter and Bohlman³ identified three histologic types of spinal cord compression. In the first type, four patients with severe, chronic mechanical cord compression exhibited distortion with flattening and destruction of the cord and secondary wallerian degeneration of the ascending and descending tracts, without anoxic or ischemic neural changes, suggesting that the damage was due to chronic mechanical compression. In the intermediate stage of compression (type II), there was vascular compression showing ischemic damage to the cord, with necrosis of the lateral columns and the ischemic watershed regions supplied by the anterior and posterior spinal arteries. In the patients with mild mechanical compression (type III), there was only focal gliosis at the site of compression, without ascending or descending tract injury. Nakano and coworkers⁴⁵ analyzed two autopsy cases and found that maximal changes occurred in the central gray matter and adjacent posterior and lateral columns. This was thought to be due to direct intermittent compression and narrowing of the transverse branches of the anterior spinal artery. This was previously observed by Bland² and confirmed more recently by Casey and colleagues.⁶² Thus, the available space for the spinal cord at the craniocervical junction is of great prognostic significance.^4,62,63

In addition to the cervical involvement described earlier, patients with RA are at higher risk for the development of compression fractures in other areas of the spine. Orstavik and associates⁶⁴ showed that patients with RA had a significantly higher risk of multiple thoracic and lumbar compression fractures than matched controls (odds ratio 2.60). In this study, presence of RA, bone mineral density, and corticosteroid use were independent predictors of vertebral deformities. In addition, there are reports of spontaneous (nontraumatic) odontoid fractures in patients with RA. Although rare, this condition should be considered in RA patients with neck pain whose work-up is otherwise unrevealing.^65,66

Extra-articular Manifestations

Extra-articular manifestations are myriad in patients with severe RA and high titers of rheumatoid factor. Pericarditis, myocarditis, and coronary vasculitis are not infrequent.^20,29,30,67 RA can present in the lungs as pleural effusions and pleuritis, intraparenchymal rheumatoid nodules, and Caplan’s syndrome (rheumatoid nodules with pneumoconiosis, diffuse pulmonary fibrosis, bronchiolitis, and pulmonary hypertension out of proportion to coexisting lung disease).^{18,29,68–70} Pleuritis is the most common thoracic manifestation (5% to 15%), and rheumatoid effusions occur in 50% of patients in the first 5 years after the onset of arthritis.⁷¹ Pulmonary fibrosis was seen in 10 of 18 patients with RA who underwent thin-section computed tomography (CT) scanning of the chest, but the plain radiographs were reported as normal.⁷² Thus, it is important that pulmonary function tests be performed in RA patients before any operative procedure and general anesthesia.

Pharyngeal dysfunction may be a manifestation of neurological involvement or floppy arytenoid cartilages, with an abnormal swallowing mechanism as a result of the disease process.

Medical Treatment

Current recommendations for the medical management of RA include the use of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs). NSAIDs and cyclooxygenase-2 (COX-2) inhibitors provide symptomatic relief but do not alter the course of the disease. A substantial number of patients are placed on corticosteroids, although the use of this class of medications is limited by side effects. The current mainstay of RA management is DMARDs. Synthetic DMARDs include methotrexate, leflunomide, sulfasalazine, minocycline, intramuscular gold, penicillamine, chloroquine, and hydroxychloroquine. Biologic DMARDs are newer agents that target the immune response. Currently, there are four such medications, three of which inhibit TNF-α (infliximab, etanercept, adalimumab) and one that inhibits interleukin-1 (anakinra). Previously, single DMARD therapy was preferred, but more recent studies have shown a substantial advantage to using combination DMARD therapy.⁷³ A recent study showed that combination DMARD therapy reduces the incidence of atlantoaxial subluxation in patients with RA compared with DMARD monotherapy.⁷⁴

Clinical Presentation

Atlantoaxial subluxation may present within 2 years of the disease, but it is unusual for myelopathy to develop early.^50,59,75 The most frequent symptom of rheumatoid abnormalities of the craniocervical junction is occipital headaches.³¹ This is typically described as occipital pain radiating to the skull vertex and aggravated by an upright posture. It was present in 60% of patients with atlantoaxial subluxation and 90% of individuals with cranial settling. Between 1977 and 1994, 780 symptomatic patients with RA affecting the craniocervical region were evaluated by Menezes.³¹ Three main categories of abnormalities were recognized from a radiographic standpoint: atlantoaxial instability, cranial settling, and primary granulation tissue masses.

Cervical myelopathy is insidious, and disability may be mistaken for progression of rheumatoid disease, rheumatoid joint dysfunction, hypothyroidism, or poor nutritional habits.^{13,25,61,76,77} The clearest indication of cervical myelopathy is progressive physical disability and the inability to carry out daily tasks.^45,61 It is difficult to detect abnormal neurological signs of myelopathy in rheumatoid patients with deforming painful arthritis and associated neuropathy. The peripheral neuropathy itself can cause areflexia. Thus, the presence of normal reflexes in a patient with advanced RA should raise the suspicion of myelopathy. We have found neurophysiologic testing with somatosensory evoked potentials to be of no use in this situation, despite some reports to the contrary.⁹

Limb paresthesia, numbness, weakness, and sphincter disturbance may herald myelopathy. Dizziness, vertigo, and syncope may be associated with vertebrobasilar ischemia. Nystagmus may be evident in this situation. Transient blackout spells were reported by 55% of individuals with cranial settling.²⁵ Gradual, progressive difficulty with ambulation was a chief complaint in 76% of individuals with cervical myelopathy. In 15% of individuals, an acute onset of quadriparesis was seen.³¹

Abnormal neurological signs in Menezes’³¹ series included brainstem evidence of internuclear ophthalmoplegia, facial diplegia, nystagmus, spastic quadriparesis, and sleep apnea, especially in patients with cranial settling. These signs, either singly or in combination, were present in 20% of individuals. An additional 20% had loss of pain and touch sensation in the distribution of the trigeminal nerve, and each patient had invagination of the odontoid process in excess of 10 mm above the foramen magnum. The cranial nerves most affected by cranial settling were the glossopharyngeal, vagus, and hypoglossal. With cranial settling, 20% of individuals had evidence of dysfunction of one or more cranial nerves.⁷⁸ Nine individuals with cranial settling had undergone previous tracheostomy for the diagnosis of rheumatoid pharyngeal dysfunction.

Radiologic Features of Cervical Spine Involvement

Radiographic changes reflect the pathologic processes described. Plain lateral cervical spine radiographs as well as anteroposterior and open-mouth views are usually obtained. At times, dynamic flexion-extension views are obtained, with the extended and flexed positions assumed by the patient without forced extremes of head position. Neurological deficits, predental space of 7 to 8 mm, abnormal radiographic pathology such as cranial settling, atrophy of the odontoid process, and subaxial subluxation justify MRI. This identifies the relationship of the cervical spine to the contained cervicomedullary junction and cervical spinal cord. It is important that MRI scans be obtained in the sagittal and axial planes using both T1- and T2-weighted modes. Dynamic views in the flexed and extended positions identify the instability as well as the manner of compression (Fig. 289-4).^56,58,79,80 Active synovitis with ligamentous involvement is best identified with the spin echo technique. Contrast-enhanced T1-weighted spin echo MRI can discriminate between joint effusion and various forms of pannus in patients with RA of the craniocervical junction. With joint effusions, Stiskal and coworkers⁵⁷ found a low signal intensity on unenhanced T1-weighted images and a high signal intensity on T1-weighted enhanced images, with a rim-like zone at the periphery in all lesions; this was redistributed with delayed images (Fig. 289-5). In hypervascular pannus, T2-weighted graded images showed high intensity, as did contrast-enhanced images. However, in fibrous pannus, there was reduced signal intensity in both T2-weighted GRE images and pre- and postcontrast T1-weighted spin echo images.⁸⁰ This is important from a surgical standpoint. In the case of fibrous hypovascular pannus, craniocervical immobilization with fusion does not result in disappearance of the ventral mass (see Fig. 289-3). However, active pannus with hypervascular tissue, like active synovitis, resolves with dorsal stabilization.

FIGURE 289-4 A, Midsagittal T1-weighted magnetic resonance image of the brain and cervical cord in the flexed position in a 42-year-old individual with rheumatoid arthritis. There is atlantoaxial dislocation with ventral compression on the cervicomedullary junction. B, Midsagittal T1-weighted image in extension. Note the reduction of the atlantoaxial dislocation.

FIGURE 289-5 A, Composite of midsagittal (left) and axial (right) magnetic resonance images through the plane of the odontoid in a 67-year-old with rheumatoid arthritis. The gadolinium-enhanced T1-weighted image shows a rim-like zone at the periphery of the lesion, with ventral cervicomedullary compression. This represents active pannus. B, Composite of midsagittal magnetic resonance images of the craniocervical junction with T1 (left) and T2 (right) weighting 3 months after dorsal occipitocervical fusion with titanium loop instrumentation and rib grafts. The pannus has completely regressed.

Thin-section CT and three-dimensional CT of the affected area provide additional information regarding the osseous integrity, as well as the relationships and extent of osteoporosis and osteopenia (Fig. 289-6).³¹

FIGURE 289-6 A, Midsagittal T2-weighted magnetic resonance image of the craniocervical junction in a 68-year-old individual with advanced rheumatoid arthritis. This patient presented with quadriparesis and a marked head tilt to the right. Note the hourglass constriction of the subarachnoid sac at the C1 level. B, Three-dimensional reconstruction of the skull and cervical spine in the patient in A. There is lateral dislocation of C1 and C2 with a 35-degree angulation. C, Composite of axial computed tomography scans through the upper (left) and lower (right) rims of the atlas arch. There is an odontoid fracture, with the superior segment adjacent to the odontoid stub. Note the fixed atlantoaxial dislocation.

Overall, MRI is the preferred method for evaluating patients with suspected rheumatoid involvement of the cervical spine. In one study, plain radiographs identified craniocervical junction disease in 32.6% of patients, CT showed disease in 41.3% of patients, and MRI identified craniocervical junction disease in 61% of patients with RA. Therefore, the false-negative rate for both plain radiography and CT was high.⁸¹

Cranial settling is reducible in 77% to 80% of individuals by means of positioning or cervical traction of up to 9 to 10 pounds over 4 to 5 days (Fig. 289-7). Cranial settling is irreducible in individuals who exhibit odontoid penetration through the foramen magnum greater than 15 mm, large pannus, fracture of the odontoid process, or cranial settling complicated by lateral or rotational dislocation in addition to the primary phenomenon (Fig. 289-8).^31,78 Complex cranial settling with posterior dislocation is considered potentially lethal at any time owing to the distraction of the vertebral artery complex. In such individuals, a fusion procedure should be done immediately.

FIGURE 289-7 A, Midsagittal T1-weighted magnetic resonance image of the brain and cervical cord in a patient with cranial settling and vertical odontoid penetration into the posterior fossa. B, Midsagittal T1-weighted image of the craniocervical junction in the same patient 48 hours after halo traction. There is reduction of the vertical odontoid penetration into the foramen magnum and relief of the cervicomedullary compression.

FIGURE 289-8 A, Composite of midline sagittal craniovertebral junction tomogram and a line drawing illustrating odontoid penetration into the foramen magnum and fracture of the odontoid process. B, Composite of axial computed tomography scans made 1 cm (left) and 3 cm (right) above the plane of foramen magnum. The subarachnoid space is opacified with iohexol. The tip of the odontoid process is anchored into the ventral medulla at the formation of the basilar artery and the two vertebral arteries.

Operative Indications

There is wide variation among natural history studies, including the results. Failure to identify and appreciate cranial settling²⁵ makes it difficult to draw conclusions about the efficacy of surgical intervention. Likewise, the identification of abnormal pathology without attempted reduction in potentially reducible lesions has led to an increased incidence of ventral decompression and dorsal occipitocervical fusion. However, there is a consensus that surgical intervention must be advocated in patients with progressive neurological dysfunction, cranial settling, and intractable pain.^{4,35,36,45,49,50,75,82} Cervical myelopathy and instability after decompressive laminectomy are urgent indications for operative intervention.

Atlantoaxial dislocation greater than 8 to 9 mm must be carefully examined with MRI. Boden,⁶³ in a 1994 publication, showed that a posterior atlantodental interval greater than 14 mm (on plain films) was generally safe. This does not include the presence of pannus or other tissues that reduce the effective diameter of the subarachnoid space. If the posterior atlantodental interval was greater than 14 mm, there was a 94% chance the patient would have no paralysis. Unfortunately, a patient with a posterior atlantodental interval of 13 mm could have a much smaller available space for the spinal cord, depending on the thickness of pannus.

Casey and colleagues,⁶² reporting on Crockard’s series, recognized high rates of postoperative morbidity and mortality in patients classified as Ranawat class IIIB (Table 289-2).⁸³ They cited a detailed investigation of a cohort of 55 such patients. The early postoperative mortality was 12.7%, and one quarter of the patients were dead within 6 months. When the spinal cord area was less than 44 mm², a poor outcome was more likely; this also correlated with patients who had an increased degree of vertical translocation. Weissman and associates,⁸⁴ in an earlier publication before the MRI era, actually proposed the same idea without a true statistical analysis. Boden⁶³ likewise recognized that when the posterior atlantodental interval was less than 10 mm preoperatively, the prognosis for return of motor function was poor. In contrast, significant motor recovery could be appreciated after surgery in patients who had preoperative intervals of 14 mm or more.

TABLE 289-2 Ranawat Classification of Neurological Deficit

Surgical Treatment

The primary treatment goals for patients with RA at the craniocervical junction are relief of neuraxial compression and elimination of instability.²⁵ Achievement of these goals is dependent on the precise identification of the pathology and motion mechanics. For treatment purposes, these lesions are divided into reducible and irreducible lesions.⁴ A reducible lesion is defined as one in which relief of compression on the cervicomedullary neural structures can be obtained by restoring the craniovertebral junction to a more anatomic relationship. This may be accomplished by positioning or cervical traction. A stabilization procedure then becomes paramount. In irreducible lesions, the basic tenet is decompression in the manner in which encroachment occurred before dorsal fixation.

All patients who require surgical attention must first be evaluated for articular and extra-articular involvement by the rheumatoid process. Nutritional status is best evaluated with a total lymphocyte count and liver function tests.³¹ A lymphocyte count less than 1000 is indicative of protein deficiency. All salicylate and NSAIDs must be discontinued for 1 week before any surgical intervention. During this time it is imperative to maintain drugs such as methotrexate and steroids for the symptomatic relief of pain. Cardiac status and pulmonary function are always evaluated in the senior author’s unit.

The senior author strongly believes that before patients undergo any other treatment for rheumatoid involvement of the craniocervical junction, an attempt should be made to align the osseous anatomy to relieve the neural compression. Traction is contraindicated only when there is a complex rotary luxation or posterior occipitoatlantoaxial dislocation.³¹ These individuals actually require an immediate stabilization procedure. All patients undergoing cervical traction should be observed in a monitored nursing setting with pulse oximetry and the capacity to monitor respiratory function. Traction is applied via a crown halo ring. This is started at 5 to 7 pounds and gradually increased to a maximum of 10 to 11 pounds, achieved at 36 hours. Periodic radiographic evaluation is essential to identify the degree of reduction and to adjust the vector of force for distraction. Mild extension to a neutral position is necessary in most individuals. If reduction is not achieved in 4 to 5 days, this should be considered an irreducible state, especially in the conditions previously described. Dorsal fusion in the face of ventral irreducible pathology can have adverse results (Fig. 289-9).

FIGURE 289-9 A, Lateral cervical radiograph in a 54-year-old individual with rheumatoid arthritis and difficulty swallowing, diplopia, and quadriparesis. Dorsal occipitocervical fusion with plate and screws and iliac crest bone graft had been performed previously to treat ventral pontomedullary compression with cranial settling, without addressing the ventral pathology. B, T2-weighted magnetic resonance image in the midsagittal plane of the craniocervical junction reveals odontoid penetration into the foramen magnum, compressing the ventral pontomedullary junction. Note the position of the vertebrobasilar arterial tree and the acquired hindbrain herniation. C, Axial T2-weighted image made 1 cm above the plane of the foramen magnum. The odontoid process is posterior to the vertebrobasilar system and compresses the ventral and right lateral medulla.

Irreducible pathology causing ventral cervicomedullary neural compression (e.g., cranial settling with odontoid invagination into the medulla) requires ventral removal of the offending pathology first.^31,78 The transoral transpharyngeal route provides a rapid, safe, and effective approach to the ventral craniovertebral junction. This procedure must be accompanied by dorsal fixation. Cranial settling mandates occipitocervical arthrodesis.²⁵

Reducible atlantoaxial dislocation is best managed with transarticular screw fixation if the lateral atlantal masses are intact and the quality of bone is satisfactory, as in a younger individual (Fig. 289-10).^{9,27,31,85–87} However, all fusions must be supplemented with bone; in the senior author’s practice, this is done with dorsal interlaminar fixation using rib graft.⁷⁸ The reported fusion rate is 98.2%.⁸⁷ The Halifax clamp for atlantoaxial dorsal fixation is associated with failure in 17% to 20% of individuals.⁷⁸ Placement of a large rectangle of iliac crest between the posterior arch of C1 and C2 with cable retention also has a high failure rate (Fig. 289-11). Internal fixation obviates the need for postoperative halo immobilization and similar measures. Dorsal occipitocervical fusion is necessary in all individuals with rheumatoid cranial settling and in those who have had resection of the rheumatoid pannus. In a few individuals with active pannus, dorsal fixation allows stabilization and reduction of the ventral soft tissue mass because the active process abates immediately with stabilization (as with active effusion in other joints). Dorsal occipitocervical stabilization necessitates the placement of bone to anchor the cervical spine to the occiput as far laterally as possible; this prevents lateral rotation as well as flexion and extension and provides for axial loading.^78,88–90 In most rheumatoid individuals undergoing dorsal occipitocervical fusion, instrumentation is essential. This is handled with a custom-contoured threaded titanium loop fixed to the skull and the upper cervical spine.^31,90 This allows bone supplementation for long-term osseous integration. Use of calvarial bone in a disabled rheumatoid patient does not add to morbidity or mortality, as questioned by several authors.^9,50 The success rate of occipital bone grafts has been well documented.^91–93 In the senior author’s experience, a modified custom-built occipitocervical shell brace has proved satisfactory for occipitocervical stabilization. This custom-molded orthosis is similar to a modified Minerva brace and has a high degree of patient acceptance and compliance.

FIGURE 289-10 Lateral cervical spine radiograph in a 72-year-old individual with severe atlantoaxial dislocation that reduced in traction. Note the transarticular screw fixation and bone obtained from the calvaria for dorsal occipitocervical fusion.

FIGURE 289-11 A, Lateral cervical radiograph in a 62-year-old woman with rheumatoid arthritis who had undergone atlantoaxial arthrodesis and postoperative halo immobilization. There is failure of the reduction, and the subsequent fusion mass has added to the cervicomedullary compression. The patient presented with quadriparesis. B, T1-weighted magnetic resonance image of the patient in A demonstrating ventral and dorsal compression of the cervicomedullary junction. This was irreducible. C, Reformatted computed tomography reconstruction of the craniocervical region through the plane of the odontoid process. The atlantoaxial dislocation is still present, and the fusion mass has slipped ventral to the posterior arch of C1. The inferior aspect of the graft had incorporated with the posterior arch of C2. The patient required ventral odontoid resection as well as dorsal bony decompression and fusion.

Transarticular screw fixation between C2 and C1 requires satisfactory width of the pars interarticularis at C2 and integrity of the lateral mass of C1—that is, no compromise by atrophy, compression, or significant osteoporosis.²⁷ Unfortunately, in about 25% to 30% of individuals who fulfill these criteria for transarticular screw fixation, the vertebral artery groove may encroach on the pars, risking injury even in the most experienced hands.⁸⁶ This can be readily identified as a potential problem by preoperative CT scans through the area of screw placement.

Several difficult situations can arise in RA patients with debilitating symptoms. For instance, with a bedridden patient who is not mobile, one must weigh the ideal treatment (transoral odontoid resection) against the practicalities of the situation. Such an individual would have a poor outcome, so the operative procedure should be tailored to his or her needs. Pain may be handled with fusion; however, significant ventral pathology would need to be addressed first. The quality of bone also plays a large part, as does the patient’s nutritional status. Likewise, the fusion may not take owing to the quality of recipient bone, tissue vascular changes, and the inability to achieve satisfactory postoperative immobilization. These are just a few of the difficulties that may be encountered in the management of patients with RA.

Following occipitocervical or cervical arthrodesis, careful follow-up is required. Clarke and coworkers⁹⁴ found that 39% of RA patients undergoing surgery for atlantoaxial subluxation subsequently developed subaxial subluxation; 54% of these patients required fusion for this new condition. Ronkainen and associates⁹⁵ reported long-term follow-up in a series of patients who underwent surgery for RA involvement of the cervical spine. Perioperative mortality was within the range reported by other authors (5.6%). However, long-term mortality over the median follow-up time of 7.5 years was 37%. In this study, age and postoperative complications were associated with higher mortality. In addition, patients with horizontal atlantoaxial subluxation fared better than those with other forms of atlantoaxial subluxation.