Cervical subluxation in rheumatoid arthritis

INTRODUCTION — The discovertebral joints in the cervical spine may be affected in patients with rheumatoid arthritis (RA), with resulting osteochondral destruction [1-3]. Cervical joint destruction in patients with RA may lead to vertebral malalignment, including subluxation, which may cause pain, neurologic deficits, and deformity.

The clinical manifestations and treatment of craniocervical (ie, cranial settling, atlantoaxial impaction, and vertical subluxation), atlantoaxial (C1 to C2), and subaxial subluxation in RA are presented here. The clinical features and general medical management of RA, as well as the differential diagnosis and general evaluation of the patient with neck pain and of cervical spine disorders, are discussed separately. (See "Clinical manifestations of rheumatoid arthritis" and "General principles and overview of management of rheumatoid arthritis in adults" and "Evaluation of the adult patient with neck pain".)

EPIDEMIOLOGY AND RISK FACTORS

Prevalence — Estimates of frequency vary depending upon the study population, imaging techniques, degree of subluxation, and other characteristics. Craniocervical junction involvement has been detected by magnetic resonance imaging (MRI) in 24 percent of patients with early rheumatoid arthritis (RA; less than 12 months' disease duration), particularly in patients with anti-citrullinated protein antibodies (ACPAs), erosive disease, and high disease activity scores [4,5].

A 2015 meta-analysis found a decrease in the prevalence of atlantoaxial subluxation in the 2000s compared with the period before the 1980s (24 versus 36 percent) [6]. These findings are consistent with the clinical experience of experts in spinal surgery that the rate of occipital-cervical fusion has decreased with the advent of more effective disease-modifying antirheumatic drugs (DMARDs) and treatment strategies.

Nonetheless, despite finding decreases from 1983 to 2001 in rates of hospitalizations for certain manifestations of severe RA (eg, rheumatoid vasculitis, splenectomy for Felty syndrome), one state-wide study in California found no significant decrease in rates of hospitalization for cervical spine surgery during this period [7].

As examples of the various studies:

●General RA population:

•An inception cohort study of 103 patients with RA (of whom 69 survived at least 20 years to have lateral radiographs of the cervical spine) that was published in 2000 documented anterior atlantoaxial subluxation and vertical subluxation in 23 and 26 percent, respectively [8]. None of these patients required surgical procedures on the cervical spine.

•A 2014 publication described 100 randomly selected Iranian patients without symptoms of cervical spine disease and a mean disease duration of 12 years that exhibited a 17 percent prevalence of radiographic cervical spine subluxation. Anterior atlantoaxial subluxation (>3 mm) was present in 10 percent, and the remainder demonstrated atlantoaxial impaction and subaxial subluxation [9].

●Hospitalized patients with RA and RA patients referred for hip or knee arthroplasty:

•In one historical review published in 1991 of 113 patients with RA referred for hip or knee arthroplasty at one institution, 61 percent had radiographic evidence of cervical spine instability at the time of such surgery [10].

•In a group of 476 hospitalized patients with RA, vertical subluxation was noted in 4 percent, all of whom were women with severe RA who also had lower cervical involvement, which was also severe in most patients [11].

●Juvenile idiopathic arthritis (JIA):

•In one series, 159 consecutive patients with juvenile chronic arthritis had cervical spine radiographs taken at age 18 [12]. In 62 percent, some changes were noted, including 41 percent with apophyseal ankylosis and 17 percent with anterior atlantoaxial subluxation and 25 percent with atlantoaxial impaction.

•In another study in one center, all consecutive patients with JIA were followed into a transition program, and cervical spine radiographs were performed [13]. Of the 57 JIA patients, 65 percent showed cervical spine lesions, and half had no symptoms. As in other observations, cervical lesions in JIA were similar to those with adult RA, except for ankylosis and hypotrophia [13].

Risk factors — Numerous characteristics have been identified as risk factors for development of cervical subluxation, including a number that are consistent with an association with more severe disease [14-17]. Some associations vary between studies or occasionally conflict, which may relate to differences in populations and cohorts studied and unmeasured confounding variables. In a 2017 systematic review and meta-analysis that limited its analysis to moderate- to high-quality studies, the following factors were associated with increased risk of cervical spine instability [16]:

●Female sex

●Positive rheumatoid factor (RF)

●Long-term glucocorticoid use

●Long RA duration

●Erosive peripheral joint disease (in hands or feet)

●Higher levels of C-reactive protein and erythrocyte sedimentation rate

Similarly, associations with cervical spine instability have been described with the following factors [10,14,15,17-19]:

●Higher disease activity scores

●Previous joint surgery

●Erosions in the hands, feet, hips, and knees, and rapidly progressive erosive peripheral joint disease

●Early peripheral joint subluxations

●Osteoporosis

●Higher levels of ACPA

PATHOGENESIS

Pathogenesis of joint injury — There are two possible mechanisms for involvement of the intervertebral joints in the cervical spine in rheumatoid arthritis (RA):

●Extension of the inflammatory process from adjacent neurocentral joints (the joints of Luschka, which are lined by synovium) into the discovertebral area.

●Chronic cervical instability initiated by apophyseal joint destruction, subsequently leading to vertebral malalignment or subluxation [20]. This may produce microfractures of the vertebral endplates, disc herniation, and degeneration of disc cartilage.

Bursal spaces exist between the cervical spinous processes. In some RA patients, bursal proliferation has led to radiographically demonstrated destruction of the spinous processes [21].

Neurologic findings may occur when the space available for the brain stem, spinal cord, or nerve roots is compromised by vertebral subluxation or pannus formation posterior to the odontoid. (See 'Anatomic outcomes of joint injury' below.)

Asymmetric apophyseal joint erosion may cause scoliosis manifested as head tilt. Joint destruction and/or spontaneous fusion often lead to reduced range of motion. Anterior atlantoaxial or subaxial subluxations may cause the head to protrude forward, leading to positive sagittal balance.

Anatomic outcomes of joint injury

●Atlantoaxial and occipitoatlantal disease – Among the joints of the cervical spine, the atlantoaxial joint is prone to subluxation in multiple directions, potentially leading to cervical myelopathy [22]. The atlas (C1) can move anteriorly, posteriorly, vertically, laterally, or rotationally relative to the axis (odontoid and body of C2):

•Abnormal anterior movement on the axis is the most common type of subluxation (figure 1). It often results from laxity of the transverse ligament induced by proliferative C1 to C2 synovial tissue, but may also occur as a result of erosion or fracture of the odontoid process (eg, dens, odontoid peg) [23].

•Posterior movement on the axis can occur only if the odontoid process has been fractured from the axis or been destroyed or if the C1 ring has been fractured.

•Vertical movement in relation to the axis is least common; it results from destruction of the lateral atlantoaxial joints or potentially from destruction of the occipitoatlantal joints. Penetration of the odontoid process into the foramen magnum reduces the space available for the (spinal) cord (SAC) and may cause the odontoid to impinge upon and deform the brainstem (figure 2) [24].

•Vertical atlantoaxial subluxation may occur in those with initial anterior-posterior subluxation. Vertical subluxations are believed to have a worse prognosis than the other varieties [25].

●Subaxial disease – Instability of the subaxial (C3 to C7) joints, which may affect more than one level, results from synovitis of the facet joints together with damage to the intervertebral discs and interspinous ligaments. This results in horizontal subluxation of one vertebral body upon another. Compression of the spinal cord, a cervical nerve root, or both may result [1].

CLASSIFICATION OF MYELOPATHY — The severity of myelopathy in patients with rheumatoid arthritis (RA) and cervical spine instability is most commonly classified according to criteria described by Ranawat in 1979, which have been termed the Ranawat classification for cervical myelopathy [26,27]:

●Class I – No neurologic deficit

●Class II – Subjective weakness with hyperreflexia and dysesthesia

●Class IIIA – Objective weakness with long-tract signs; remains ambulatory

●Class IIIB – Objective weakness with long-tract signs; nonambulatory and quadriparetic

These criteria are widely used in research to describe the neurologic severity of disease in patients under study.

CLINICAL MANIFESTATIONS

Symptoms — Involvement of cervical joints may result in significant pain; the earliest and most common symptom of cervical subluxation is pain radiating superiorly towards the occiput [28]. However, passive range of motion may be normal in the absence of muscle spasm. (See 'Physical findings' below.)

Symptoms of spinal cord compression that indicate a need for immediate attention and intervention are described below. (See 'Symptoms requiring immediate attention and intervention' below.)

Some symptoms of cord compression may not be distinguishable without imaging from those of vertebral artery compression. (See 'Diagnosis and diagnostic evaluation' below.)

Symptoms of subluxation depend upon the affected anatomic region; in addition to pain, the symptoms may include:

●A sensation of the head falling forward or a "clunking" sensation upon flexion of the cervical spine.

●In patients with atlantoaxial subluxation, symptoms may include those of a myelopathy, sensory loss, paresthesias in the C2 area (greater occipital neuralgia), decreased sensation in the distribution of the fifth cranial nerve, and nystagmus.

●Subaxial subluxations, which narrow the intervertebral foramina, may cause radiculopathy, with symptoms and findings depending upon the affected nerve root (table 1), in addition to myelopathy from central stenosis. Subaxial disease may involve more than one level and can occur without concomitant myelopathy.

●Vertical subluxation of the odontoid process of C2 may cause transient episodes of medullary dysfunction (such as respiratory irregularity) and the potential for vertebral artery compression [1,29,30]. While sudden death due to medullary dysfunction from compression has been reported to occur in up to 10 percent of cases, the true frequency is unknown due to the difficulty in studying the cause of death [31,32].

Symptoms of vertebrobasilar insufficiency (VBI) may be present and include dizziness (present in approximately 60 percent), sometimes with a syncopal episode; vertigo; bilateral leg weakness, "drop attacks" (in which the patient feels suddenly weak in the knees and falls), and hemiparesis; diplopia and visual loss; numbness and paresthesia; and oscillopsia (a sensation that surroundings are in constant motion) due to involvement of cranial nerve VIII [33]. (See "Posterior circulation cerebrovascular syndromes".)

Physical findings — Physical findings relating to the spine suggestive of subluxation include:

●Loss of cervical lordosis

●Scoliosis

●Resistance to passive spine motion

●Abnormal protrusion of the anterior arch of the atlas felt by the examining finger on the posterior pharyngeal wall

●Torticollis in children with juvenile idiopathic arthritis (JIA) [34]

In addition, neurologic findings appropriate to the symptoms described above may be seen, including:

●Signs of myelopathy (see "Cervical spondylotic myelopathy", section on 'Clinical presentation'):

•Increased deep tendon reflexes

•Extensor plantar responses

•Hoffman sign

•Finger escape sign

•Pronator drift

•Muscle weakness, spasticity, or muscle atrophy

•Gait disorders, including broad based gait, and difficulty with tandem gait

●Signs of radiculopathy (seen in subaxial subluxation) (table 1) (see "Clinical features and diagnosis of cervical radiculopathy", section on 'Clinical features'):

•Decreased deep tendon reflexes (seen in radiculopathy)

•Weakness

•Sensory loss

•Positive Spurling sign

●Signs of cranial nerve dysfunction (from compression of the brainstem or descending tract of cranial nerve V) [26]:

•Dysphagia from compression of vagus and glossopharyngeal nerves

•Dysarthria from compression of hypoglossal nerve

•Loss of facial sensation

•Tinnitus and vertigo

●Signs of vertebrobasilar compromise, such as the following [35] (see "Posterior circulation cerebrovascular syndromes"):

•Limb weakness

•Gait and limb ataxia

•Oculomotor palsies

•Oropharyngeal dysfunction

IMAGING FINDINGS

Conventional radiography — Among patients with atlantoaxial subluxation, plain radiographic views of the cervical spine (anteroposterior, lateral, open-mouth, flexion, and extension) may reveal more than the normal separation between the odontoid process (eg, dens, odontoid peg) and the C1 arch, referred to as the atlantodental interval (ADI), which in adults is abnormal if greater than 3 mm or in children if greater than 5 mm (image 1) [29,36]. Separation between C1 and C2 (anterior subluxation) of 9 mm or more or a posterior atlantodental distance of less than 14 mm is associated with an increased incidence of cord compression [37-39]. In addition, if the space available for the (spinal) cord (SAC) is less than 13 mm anywhere in the cervical region, there is an increased risk for neurologic impairment.

The cervical spine may be difficult to visualize effectively in patients with rheumatoid arthritis (RA) using conventional radiographic techniques because of osteopenia, the small size of the multiple joints in the cervical spine, the large mass of soft tissue surrounding the spine, and the lower borders of the occipital bones, which obscure visualization. In addition, the usual landmarks may be obliterated in advanced disease [40].

CT scan — Computed tomography (CT) can demonstrate bony anomalies such as osseous erosions not seen well on plain films or magnetic resonance imaging (MRI), although CT is not as useful as MRI for soft tissue imaging, such as evaluation of the neural structures and degree of pannus formation. In patients with C1 to C2 subluxation, CT can demonstrate spinal cord compression by revealing the loss of subarachnoid space, attenuation of the transverse ligament, and bony and soft tissue changes (image 2) [41,42].

The reformatted sagittal CT scan can precisely document the position of the odontoid with respect to the foramen magnum and the relationships among the upper cervical vertebrae [43]. Thus, CT can help determine the best surgical technique to be used, including the type, size, and trajectory of implants. (See 'Treatment' below.)

A contrast-enhanced CT scan can demonstrate vascular anomalies and inflammatory soft tissue proliferation in patients unable to undergo MRI, although an MRI is generally superior for imaging such tissues [44].

MRI — Magnetic resonance imaging (MRI) is particularly valuable in the assessment of cervical spine disease in RA and for the detection of spinal cord compression because it permits visualization of the pannus producing cord compression, the spinal cord, nerve roots, and bone (image 3) [45,46]. MRI has high sensitivity for detecting inflammatory changes in the joints even before instability develops [47]. The development of neurologic dysfunction is strongly associated with MRI evidence of spinal canal stenosis, particularly in patients with evidence of upper cervical cord or brainstem compression or evidence of subaxial myelopathy (figure 2) [48].

In a prospective study of 41 consecutive patients with RA who had an MRI of the cervical spine for neurologic symptoms or neck pain (with or without plain radiographic evidence of subluxation), 58 percent had clinical evidence of myelopathy (Ranawat class II or III). There was a strong correlation between the presence of myelopathy and MRI evidence of stenosis of the spinal canal (posterior atlantodental interval [PADI] <14 mm), compression of the spinal cord, and high signal intensity in the spinal cord on T2-weighted and/or short tau inversion recovery (STIR) images [48]. (See 'Classification of myelopathy' above.)

Bone marrow edema (BME) can be observed by MRI in patients with early cervical spine involvement as high signal intensity in the marrow on T2-weighted images with fat suppression and/or STIR images; the edema may be seen in the odontoid process, in the vertebral endplates, and in the subaxial interapophyseal joints [49].

A dynamic (flexion-extension) MRI clearly delineates the relationship between the odontoid, foramen magnum, and cervical spinal cord, but prolonged flexion should be performed with caution because of the risk of cord compression [40]. In addition, gradient-echo MRI pulse sequences provide reliable visualization of the transverse atlantal ligament, permitting the clinician to distinguish rupture from stretching of the ligament and to visualize pannus compressing the cord [50].

One drawback of MRI is that it often underestimates the degree of atlantoaxial subluxation when compared with flexion-extension plain film radiography. This discrepancy was illustrated in a series of 23 patients with RA or juvenile idiopathic arthritis (JIA) who had both radiographs and MRI with flexion and extension views performed within a one-month time frame [51]. After accounting for magnification on the plain films, the measured atlantoaxial subluxation by MRI was less than that noted on radiographs in 19 of the 23 patients; in the most extreme case, the measured distance differed by 7 mm. The main reason for the difference is attributed to the different position of the patient during these two examinations. Radiographs are taken with the patient sitting or standing and gravity pulls the head downwards when the neck is flexed, which helps the maximal extent of atlantoaxial subluxation to be reached. MRI is performed with the patient supine, making it difficult to attain an adequate degree of neck flexion to elicit the full extent of atlantoaxial subluxation.

SYMPTOMS REQUIRING IMMEDIATE ATTENTION AND INTERVENTION — The symptoms of spinal cord compression that demand immediate attention and intervention by a surgical specialist with expertise in cervical spine instability include [52]:

●A sensation of the head falling forward upon flexion of the cervical spine

●Changes in levels of consciousness

●"Drop" attacks, a sudden fall without loss of consciousness or a physical trigger

●Loss of sphincter control

●Respiratory dysfunction

●Dysphagia, vertigo, convulsions, hemiplegia, dysarthria, or nystagmus

●Peripheral paresthesias without evidence of peripheral nerve disease or compression

●Lhermitte phenomenon, an electric shock-like sensation in the neck radiating down the spine or into the arms, produced by forward flexion of the neck

●Imbalance not explained by rheumatoid involvement of the hips, knees, ankles, and feet

●Hand clumsiness and dropping objects not explained by rheumatoid hand involvement

Some of these symptoms may be due to compression of the vertebral arteries, which wind through foramina within the lateral aspects of C1 and C2. Findings on magnetic resonance imaging (MRI) and angiography (magnetic resonance angiography [MRA] or computed tomography angiography [CTA]) may help distinguish between spinal cord or brainstem compression and vertebral artery insufficiency. (See 'Imaging findings' above.)

DIAGNOSIS AND DIAGNOSTIC EVALUATION

Diagnosis — The diagnosis of cervical subluxation is made by radiologic imaging, which is typically performed in asymptomatic patients undergoing preoperative evaluation and in patients with pain or other symptoms or findings suggesting cervical myelopathy or nerve root impingement. The degree of subluxation at a given site can provide an estimate of the risk of clinically significant instability that may result in neurologic compromise. (See 'Conventional radiography' above and 'MRI' above.)

Diagnostic evaluation — Patients suspected of cervical subluxation should undergo a detailed history and exam with particular attention to symptoms and findings of myelopathy, nerve root compression, and vertebrobasilar insufficiency (VBI). (See 'Symptoms' above and 'Physical findings' above and 'Symptoms requiring immediate attention and intervention' above.)

The assessment, including the imaging evaluation, is guided by the clinical presentation and initial imaging findings, and particularly by whether symptoms or signs of neurologic compromise are present:

●Asymptomatic patients and those requiring a general anesthetic – Routine imaging is not required for asymptomatic patients without neurologic findings; however, we obtain a plain radiograph cervical spine series in all patients who need a general anesthetic because subluxation is not always symptomatic [53], and neck positioning required for intubation may be fatal or cause paralysis in the setting of spinal instability. The appropriate images include upright (preferably standing) anteroposterior, open-mouth odontoid, and lateral radiographs of the cervical spine with additional lateral images taken in flexion and extension.

In patients with deformity, instability, or narrowing (<14 mm) of the space available for the (spinal) cord (SAC), magnetic resonance imaging (MRI) of the cervical spine is indicated to assess the spinal cord and brainstem [39,54]. Significant widening of the atlantodental interval (ADI) is often cited as an indication for surgery to fuse C1 to C2. There is no consensus on the magnitude of the ADI that should mandate surgery. The guidelines for ADI are variable because the SAC and the likelihood of paralysis are not correlated with ADI. The posterior atlantodental interval (PADI), by contrast, is closely related to the SAC and risk of paralysis [39].

Spinal deformity and instability may not be evident on MRI alone, and plain radiographs are required even if an MRI has already been done.

●Mild nonspecific neck or occipital pain (without neurologic abnormalities and no history of trauma) – Patients with rheumatoid arthritis (RA) with mild, nonspecific neck or occipital pain who lack any neurologic abnormality and have not sustained trauma should be evaluated in the same way as asymptomatic patients who need a general anesthetic. The initial step in such patients is by performing plain radiographs of the cervical spine, as described.

Patients who have radiographic subluxation >5 mm and/or atlantoaxial instability but minimal symptoms should be followed clinically; if there is symptomatic progression, repeat imaging should be done to confirm changes, and patients should undergo surgical consultation.

The frequency of follow-up in patients who do not require further intervention initially is individualized. Patients should be followed for signs of myelopathy; we generally see patients back in six months to one year with repeat plain radiographs and MRI, or sooner if symptoms progress. If there has been no change in signs, symptoms, and imaging, the follow-up interval may be increased. Patients should be referred for a surgical opinion if signs or symptoms have developed, pain cannot be controlled, or deformity, instability, or stenosis has progressed (SAC <14 mm), or if signal changes in the spinal cord are evident. Patients should be instructed to make their home safe to avoid falls and referred to physical therapy for gait training. (See 'General care' below.)

●Mild neck or occipital pain, with history of trauma – Patients presenting with minor symptoms following trauma should undergo computed tomography (CT) of the cervical spine. If a fracture or instability is identified, the patient should immediately be immobilized and transferred to an emergency department for spine surgery evaluation.

●Severe pain and/or neurologic signs or symptoms following trauma – These patients should immediately be immobilized and transferred to an emergency department for spine surgery evaluation.

●Symptoms or signs suggesting possible cord compression or radiculopathy without trauma – MRI is the radiologic modality of choice in evaluating for possible spinal cord compression [55]. Plain radiographs as described above for asymptomatic patients who need a general anesthetic should also be ordered to rule out deformity and dynamic instability.

●Patients unable to undergo MRI – A contrast-enhanced CT scan can be useful to exclude vascular anomalies and diagnose inflammatory soft tissue proliferation in patients unable to undergo magnetic resonance imaging (MRI; eg, those with aneurysm clips, body implants, wires or plates, some heart valves, some implanted electrodes) [44].

●Patients with symptoms of vertebrobasilar insufficiency – In addition to the plain films and MRI recommended above for asymptomatic patients requiring general anesthesia, patients with signs or symptoms of VBI should undergo a CT angiogram, MR angiogram, or formal angiogram. Consulting with a neuroradiologist is helpful to determine the best choice at your institution. The study may also need to be done in neutral, as well as with head rotation and/or flexion/extension to identify dynamic compromise of the vertebral arteries. Close communication will assure that an invasive study is warranted and is performed correctly.

●Role of EMG – Electromyography (EMG) is not indicated for problems limited to the craniocervical or atlantoaxial regions. If the history or exam suggest radiculopathy, an EMG of the affected extremity may be useful to localize the lesion and to differentiate radiculopathy from myelopathy and peripheral neuropathy.

MRI is the modality of choice for early diagnosis of cervical involvement because it has high sensitivity in detecting inflammatory changes in the joints even before instability develops [47]. The information gained from MRI is sufficiently additive to warrant the increased cost of this procedure, particularly if surgery is contemplated.

Differential diagnosis — RA patients presenting with neck pain, myelopathy, radiculopathy, or VBI may be symptomatic from myriad conditions unrelated to cervical spine instability. The differential diagnosis for each complaint is the same as that for patients without RA. (See "Evaluation of the adult patient with neck pain" and "Cervical spondylotic myelopathy", section on 'Differential diagnosis' and "Clinical features and diagnosis of cervical radiculopathy", section on 'Differential diagnosis' and "Posterior circulation cerebrovascular syndromes".)

TREATMENT

Indications for surgery — Patients with cervical subluxation are treated medically and/or surgically based largely upon the presence or absence of signs of spinal cord compression and the degree of spinal instability or hypermobility [26].

The indications for surgery include:

●Neurologic compromise (myelopathy and/or radiculopathy)

●Vertebrobasilar insufficiency (VBI)

●Radiographic spinal instability [39,56]:

•Cranial settling with brainstem compression

•Atlantoaxial subluxation with posterior atlantodental interval (PADI) <13 mm on magnetic resonance imaging (MRI)

•Subaxial subluxation with space available for the (spinal) cord (SAC) <13 mm on MRI

●Unstable fractures

●Stenosis with spinal cord signal changes on MRI

●Severe unremitting pain.

Patients with minimal neurologic symptoms and minor degrees of radiographic subluxation can be followed periodically (initially in six months to one year, and then less frequently if follow-up exams are stable). Plain radiographs (including flexion and extension) and an MRI are recommended, along with a careful physical exam.

Timing of surgery — Progressive myelopathy, unstable fractures, and VBI are the most worrisome conditions and mandate urgent referral. The timing of surgery must be individualized based upon the severity of the findings and the patient's general health. Although surgery is still beneficial in patients with myelopathy, the risk of surgery, including mortality, is substantial when it is delayed [30]. Surgery is indicated for radiographic evidence of instability and should be considered before patients become neurologically impaired.

Comorbidities such as osteoporosis, heart disease, and malnutrition may need to be addressed to optimize the status of the patient before surgery.

Medications, including anticoagulants and disease-modifying antirheumatic drugs (DMARDs), also influence the timing of surgery. Close coordination between surgeon, rheumatologist, and other medical care providers is essential to assure timely intervention and to decrease complications. (See "Preoperative evaluation and perioperative management of patients with rheumatic diseases".)

Temporary versus permanent spinal immobilization — Patients with instability who are awaiting surgery, or in whom surgery is contraindicated, can be immobilized in a hard or soft collar to diminish neck pain and prevent repeated spinal cord irritation with neck flexion.

A hard collar provides somewhat more protection of the neural structures than a soft collar, but neither option provides rigid immobilization, or absolute safety in the event of a motor vehicle collision or fall. The collar typically does not need to be worn at night or at rest, but it is important to avoid neck flexion by using only thin pillows.

A halo is occasionally required in severe cases of instability or fracture, but respiratory compromise may occur, especially in older adult patients and those with preexisting pulmonary disease. We rarely use halos for an extended time due to problems with pin site infection and loosening.

General care — All patients should be advised to make their home environment safe to prevent falls and look out for the warning symptoms that should prompt further evaluation (eg, increased neurologic complaints, severe pain, or deformity of their neck). Physical and occupational therapists can help with gait training and provide ambulatory aids and other assistive devices. Social workers may be consulted to determine the safest and most appropriate living arrangements before and after surgery, or when surgery is not an option.

All patients should be "medically optimized," including treatment to optimize control of their rheumatoid arthritis (RA), and treating underlying osteoporosis, vitamin deficiency (especially low vitamin D to prevent fractures and allow healing of fusions), malnutrition, and infection (eg, urinary tract, dental, skin, and other infections).

Anesthetic considerations for all procedures — When anesthesia is indicated for any procedure, the stability of the spine should be assessed radiographically, if feasible (see 'Diagnostic evaluation' above). If instability is present or the question has not been resolved prior to the procedure, we consider video laryngoscopy to avoid neck manipulation.

Indications for nonurgent surgery — Patients with intractable neck pain, occipital neuralgia, and minor degrees of hypermobility and spinal stenosis may be candidates for nonurgent surgery. These patients should be "medically optimized" and referred semielectively.

We recommend a surgical consultation for patients whose SAC is <14 mm at any level on plain radiographs, or <13 mm on advanced imaging (MRI or computed tomography [CT]). The PADI is a direct measurement of the SAC and is a better predictor of paralysis than the atlantodental interval (ADI), which is an indirect surrogate for the SAC [39].

Other indications for referral to a surgeon include evidence of hypermobility on flexion/extension films at a relatively stenotic segment or signal change in the cord on MRI. Cranial settling (vertical subluxation) is a worrisome finding and mandates a surgical referral. Atlantoaxial subluxation occasionally appears to decrease over time, but this may be a manifestation of progressive cranial settling. As the ring of C1 descends on the odontoid (increasing Clark station) (figure 3), the ADI may decrease, but the projection of the odontoid process into the foramen magnum is a greater concern than atlantoaxial subluxation. Prophylactic surgery in these cases may avoid a neurologic catastrophe, and earlier intervention may decrease the magnitude of surgery and diminish complications.

Surgical options and trends — Surgical evaluation and operative procedures should be performed by an orthopedic or neurosurgical expert in surgical techniques for cervical spine instability, given their complexity and nuances [26]. As examples, anterior procedures are occasionally required for cases of severe deformity and stenosis, but surgery is generally performed posteriorly in patients with RA. Decompression is indicated for stenosis, unless it is mild and asymptomatic. Decompression can sometimes be accomplished indirectly through realigning and fusing the spine. Only rarely would a decompression without a fusion be considered. Fusions (permanently joining vertebrae together) may include C1 to C2 alone or extend into the subaxial and thoracic spine and/or to the occiput.

Improvements in the management of RA, including the availability of more effective therapies, has decreased the need for surgery and markedly diminished the need for transoral odontoidectomy and fusion to the occiput. Most vertical subluxation occurs at C1 to C2. This recognition has allowed fewer fusions to the occiput, since fusing C1 to C2 typically arrests further vertical subluxation.

Subaxial subluxation was historically a common finding after occipital C2 or C3 fusions. Although this complication happens less commonly with C1 to C2 fusions, the tendency now is to fuse the entire cervical spine from C1 to the upper thoracic spine to treat neck pain and avoid adjacent segment disease with neurologic compromise, worsening pain, subluxation, and deformity. Traction is still occasionally used to realign the spine, though less frequently than in the past. Traction may be administered preoperatively, intraoperatively, or between stages in multistage cases. Subaxial instability may also develop from adjacent segment disease due to spontaneous ankylosis, especially in patients with juvenile idiopathic arthritis (JIA) [56].

Medical therapy — Patients with severe subluxation but without signs of cord compression are at risk for severe injury and perhaps death due to a variety of insults. These include minor falls, whiplash injuries, and intubation. Stiff cervical collars are used primarily for symptoms of discomfort; however, they do not adequately prevent flexion of the cervical spine. Although the subject of some controversy, stiff cervical collars may be prescribed for stability; in one report, more than 50 percent of such patients benefited from this modality [57,58]. In some patients, halo traction may be of benefit, typically followed by surgery.

Collars that are not rigid (and, therefore, that are more comfortable for the patient) give reassurance to both the clinician and the patient but provide little structural support. Soft collars may help remind the patient to restrict certain activities that may be detrimental. There is no evidence that collars change the natural history of the disease, and they are not helpful for atlantoaxial impaction.

Spinal manipulation is contraindicated in patients with cervical spine instability.

The role of neck muscle strengthening exercises is uncertain. A decrease in anterior atlantoaxial subluxation was noted in a subgroup of seven patients with RA and unstable atlantoaxial joints during active isometric neck flexor muscle contraction, but there was no significant change in those without anterior atlantoaxial subluxation and those with stable joints [59]. While these data suggest that isometric neck flexor exercise is probably safe, the efficacy of neck flexor muscle strengthening for symptoms related to subluxation, radiographic progression, and other important patient outcomes was not assessed in this study. In contrast with the neck flexors, isometric neck extensor muscle tightening worsened radiographically apparent atlantoaxial subluxation in those with unstable articulations. Thus, while further investigation of neck flexor strengthening may be warranted, isometric exercise of the neck extensors should be avoided.

Patients who have pain due to irritation of C2 nerve root but who do not have evidence of cord compression may benefit from agents used for chronic neuropathic pain (see "Approach to the management of chronic non-cancer pain in adults", section on 'General approach'). These patients may obtain some benefit from local nerve blocks, although the relief is generally temporary.

Surgery

Preoperative planning for cervical spine surgery — CT is particularly useful for surgical planning [54]. Although CT has been largely replaced by MRI as the modality of choice to evaluate the neural structures and degree of pannus formation, CT can demonstrate bony anomalies not seen well on plain films or MRI and can help determine the best surgical technique to be used, including the type, size, and trajectory of implants. For example, depending on the patient's anatomy, the surgeon may elect to use screws placed into the pars interarticularis, pedicle, or lamina of C2 [60]. These screws in the axis are typically connected to screws placed into the lateral masses of C1 by small rods. Alternatively, cables placed around the posterior elements of C1 and C2 can be used alone or in combination with screw/rod fixation, or with transarticular screws, which cross the C1 to C2 joints.

Benefits of surgical intervention — Patients with subluxation and signs of spinal cord compression have a grave prognosis without surgical intervention to provide stability of the spine [29,61]. Although surgery for atlantoaxial subluxation has attendant risks, early operative treatment may delay the detrimental course of cervical myelopathy in RA [30,61,62]. (See 'Prognosis' below.)

The benefits offered by surgical management of patients with atlantoaxial subluxation who have myelopathy include an improved survival rate, an improvement in myelopathy in some patients, and a decreased risk of neurologic progression. The beneficial effects of surgery were illustrated in a 2003 observational study that compared 19 patients with symptomatic atlantoaxial subluxation who underwent laminectomy and occipitocervical fusion with 21 others who were managed conservatively [63]. The 5- and 10-year survival rates for those who underwent surgery were 84 and 37 percent, respectively. In contrast, none of the 21 patients managed conservatively survived more than eight years. Neurologic improvement was noted in 68 percent following surgery, while, in the nonoperative group, 76 percent had neurologic deterioration.

Surgery is generally well tolerated. In a prospective study of 532 patients with RA and with subluxations of the cervical spine seen between 1974 and 1999, 217 underwent surgery, of whom only 11 (5 percent) experienced residual neck pain or neurologic symptoms; however, the mortality rate was significant in high-risk, neurologically impaired patients [30].

Surgery should be considered carefully and on an individualized basis among patients with subluxation but without signs or symptoms of cord compression. In this setting, operative stabilization may be considered for radiographic evidence of instability to prevent neurologic deterioration, or for unremitting neck pain. In one series of 84 patients with some form of subluxation but without cord or brainstem lesions, one-fourth worsened, and one-fourth improved without surgery over 5 to 14 years of follow-up [64].

Some data support the hypothesis that early C1 to C2 fusion for atlantoaxial subluxation, before the development of superior migration of the odontoid (also known as cranial settling or vertical subluxation), decreases the risk of further progression of cervical spine instability. A retrospective study of 110 patients with RA who underwent cervical spine fusion noted two major findings on follow-up [65]:

●Fifteen percent developed cervical instability; this occurred in 5.5 percent of those with an initial C1 to C2 fusion for atlantoaxial subluxation and in 36 percent of those with an initial occiput to C3 fusion for atlantoaxial subluxation and superior migration of the odontoid.

●No patient with C1 to C2 fusion for atlantoaxial subluxation subsequently developed superior migration of the odontoid.

A limiting factor is that the incidence of sustained neurologic deterioration related to surgery may be as high as 6 percent [66]. As a result, a skilled surgical team and a careful assessment of each patient are important elements of any therapeutic regimen.

Surgical outcomes — The prognosis for patients with surgery appears to be improving due, in part, to earlier referral, enhanced technique, and better perioperative management [67-69]. As an example, the outcomes of 27 patients with RA who had cervical fusions in the period of 1991 to 1996 (late cohort) were compared with those of 32 individuals whose surgery occurred in the period of 1974 to 1982 (early cohort) [67]. Only 7 percent of patients in the more recent group had severe cervical myelopathy prior to surgery, versus 34 percent in the earlier cohort. Compared with the early group, the late cohort had fewer early postoperative deaths (0 versus 9 percent), complications (22 versus 50 percent), failed surgeries (15 versus 28 percent), and reoperations (11 versus 20 percent). Among patients in the more recent cohort in whom there was sufficient information to judge a change in neurologic status with surgery (18 patients), improvement in and maintenance of the preoperative level of function were noted three months after surgery in one-third and two-thirds, respectively. A subsequent analysis of 224 cases managed surgically over 30 years (between 1981 and 2011) at the same institution revealed that patients treated in the later cohort had surgery at an earlier stage and were more likely to be treated with C1 to C2 fusion than occipital-cervical fusion. Over time, outcomes improved and the mortality rate decreased [68].

A systematic literature review identified 23 observational studies describing the neurologic outcome after surgery for 752 patients [61]. Patients with Ranawat I (asymptomatic patients with no neurologic deficit) and II (patients with subjective weakness with hyperreflexia and dysesthesia) had only rare deterioration of their neurologic status. Ranawat III patients (those with objective weakness and long-tract signs) typically did not recover completely (see 'Classification of myelopathy' above). The 10-year survival rates mirrored the Ranawat class and ranged from 77 to 30 percent for Ranawat I (no deficit) and IIIB (nonambulatory patients with objective weakness and long-tract signs), respectively [61]. Outcomes were better with surgery than conservative treatment in all patients with neurologic involvement, but were similar for asymptomatic patients with no neurologic deficit (Ranawat I). Given the limits of observational data, randomized trials have been proposed, but have not been reported, and the ideal treatment for asymptomatic patients with radiographic instability remains to be determined [70].

Even though patients falling in the Ranawat IIIB class have a significantly worse outcome than all other groups [61], surgery may still offer the best quality of life and survival for these severely disabled patients [71]. Ideally, surgery should be offered before a significant neurologic deficit occurs.

The decompression and stabilization may need to extend into the subaxial spine. In one series, histopathologic studies of the brain stem and spinal cord of nine patients with end-stage RA revealed significant subaxial myelopathy in the cervical spine related directly to compression, stretching, and movement of the spinal cord [72].

Lateral mass screws are generally used in the subaxial spine, but osteoporosis, synovitis, and bone erosion may cause the fixation to be suboptimal. Pedicle screw fixation using stereotactic guidance has been used for stabilization [73]. Because the diameter of cervical pedicles is very small, this is considered a procedure with significant risk. The use of full-scale, three-dimensional models in preoperative planning may lessen morbidity [74].

Patients with RA requiring spine surgery present special challenges related to the disease itself as well as the medical management. Glucocorticoid treatment increases the risk of osteoporosis, which in turn leads to a higher rate of pseudarthrosis. The immunosuppressive effects of glucocorticoids, conventional DMARDs, and biologic agents increase the risk of infection and wound healing problems, and the DMARDs and biologic agents should be temporarily held in the perioperative period. Cardiovascular and pulmonary involvement increase the risk of surgery, and medical management must be optimized before, during, and after surgery. The joint manifestations of RA limit postoperative mobility and self-care and complicate rehabilitation. Despite these problems, a careful, team approach to care will mitigate the risks, and good outcomes can be achieved [75].

PREVENTION — In patients with rheumatoid arthritis (RA) who lack cervical subluxation, optimizing RA treatment by use of disease-modifying antirheumatic drugs (DMARDs) may help prevent or substantially delay such injury (see "General principles and overview of management of rheumatoid arthritis in adults"). Limited evidence suggests that the early administration of combination therapy consisting of DMARDs may help prevent the development of cervical spine subluxation. As an example, 195 patients with RA of recent onset (two years or less) were randomly assigned to a regimen of sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone or to sulfasalazine alone [76]. Atlantoaxial impaction or anterior subluxation developed in 2 and 7 percent of the sulfasalazine alone group, respectively, but in none of those receiving combination therapy after two years of treatment. DMARD treatment was unrestricted after two years. At five years of follow-up, the occurrence of anterior atlantoaxial subluxations was associated with initial single DMARD therapy [77]. Atlantoaxial impaction or anterior subluxation developed more often in the initial single-therapy group compared with the initial combination therapy group (6 and 14 percent versus 1 and 3 percent, respectively). These results support the notion that early aggressive treatment of RA with the goal of achieving disease control reduces the subsequent development of cranial instability.

In a study of 91 patients with RA treated with biologic DMARDs, the 44 patients without neck involvement at baseline were much less likely to develop neck radiographic progression than those 47 RA patients who had already developed neck involvement (7 versus 72 to 79 percent), implying that treatment before neck involvement occurs may delay onset [78].

PROGNOSIS — The early aggressive treatment of rheumatoid arthritis (RA) appears to reduce the incidence of cervical spine involvement and thus improves prognosis. However, once cervical spine involvement occurs, medical therapy may not improve the prognosis [77,79]. The onset of atlantoaxial subluxation alone is not inexorably associated with neurologic dysfunction or with an increased risk of death [80]. Although radiographic progression is common, it does not always correlate with neurologic deterioration [28,64,81-83]. Patients with plain film radiographic evidence of cervical subluxation, with or without neurologic symptoms, have a five-year mortality rate of 17 percent [24].

However, some patients with severe dislocation may be at risk of death. In one series of 104 consecutive autopsies of patients with RA, 11 cases of severe dislocation were found [32]. In all 11, the odontoid protruded posterosuperiorly and impinged on the medulla within the foramen magnum. In 5, spinal cord compression was determined to be the only cause of death.

Patients with subluxation and signs of spinal cord compression have a poor prognosis without surgery. In this setting, myelopathy may progress rapidly, and death may quickly ensue [61,84]. As an example, in a study of 21 patients with atlantoaxial subluxation and with signs of myelopathy who were managed medically, neurologic deterioration occurred in 16 of 21 (76 percent), and all were unable to walk within three years of follow-up [63]. None survived more than eight years. A systematic review of the literature revealed neurologic deterioration was almost inevitable in Ranawat II, IIIA, and IIIB patients (ie, those with findings to indicate a neurologic deficit) treated nonoperatively. The 10-year overall survival rate was 40 percent [61].

Magnetic resonance imaging (MRI) findings are helpful in determining prognosis. As an example, among 82 patients with MRI evidence of cord compression, 11 deteriorated and 9 required surgical intervention. Of those that required surgery, 6 had axial impingement/compression and 2 had subaxial impingement/compression. One other patient had vertical impingement/compression [85]. Surgery was performed due to a combination of pain and progressive neurologic deficits.

Patients with juvenile idiopathic arthritis (JIA) require close monitoring with repeat MRIs because they may experience progressive osseous and structural changes with minimal symptoms [86].

An inability to walk preoperatively also confers a poor prognosis. In one study, only 20 percent of patients with atlantoaxial subluxation who were nonambulant at the time of surgery improved after treatment [87].

SUMMARY AND RECOMMENDATIONS

●Cervical joint destruction in patients with rheumatoid arthritis (RA) may lead to vertebral malalignment (eg, subluxation), causing pain, neurologic deficit, and deformity. Risk factors for cervical subluxation include longer duration of RA, more active synovitis, higher levels of inflammatory markers, rapidly progressive erosive peripheral joint disease, and early peripheral joint subluxations. Both atlantoaxial and subaxial (below C2) joints may be involved. Estimates of the prevalence of cervical involvement among those with RA vary widely; fewer patients in the era of biologic therapy appear to require surgery compared with the 1990s. (See 'Epidemiology and risk factors' above.)

●The atlantoaxial joint is prone to subluxation in multiple directions, potentially leading to cervical myelopathy. The atlas (C1) can move anteriorly, posteriorly, vertically, laterally, or rotationally relative to the axis (odontoid and body of C2). Abnormal anterior movement on the axis is the most common type of subluxation; it often results from laxity of the transverse ligament induced by proliferative C1 to C2 synovial tissue, but may also occur as a result of erosion or fracture of the odontoid process. (See 'Anatomic outcomes of joint injury' above.)

●The two possible mechanisms for involvement of the intervertebral joints in the cervical spine in RA are extension of the inflammatory process from adjacent neurocentral joints (the joints of Luschka, which are lined by synovium) into the discovertebral area; and chronic cervical instability initiated by apophyseal joint destruction, subsequently leading to vertebral malalignment or subluxation. (See 'Pathogenesis of joint injury' above.)

●Involvement of cervical joints may result in significant pain. However, passive range of motion may be normal in the absence of muscle spasm. The earliest and most common symptom of cervical subluxation is pain radiating superiorly toward the occiput. Additional signs and symptoms of subluxation include slowly progressive spastic quadriparesis; sensory findings, including painless sensory loss in the hands or feet; transient episodes of medullary dysfunction (such as respiratory irregularity); and others. Sudden death may occur. Symptoms of spinal cord compression may also result from compression of the vertebral arteries. The signs and symptoms of spinal cord compression that demand immediate attention and intervention include (see 'Symptoms' above and 'Symptoms requiring immediate attention and intervention' above):

•A sensation of the head falling forward upon flexion of the cervical spine

•Changes in levels of consciousness

•"Drop" attacks

•Loss of sphincter control

•Respiratory dysfunction

•Dysphagia, vertigo, convulsions, hemiplegia, dysarthria, or nystagmus

•Peripheral paresthesias without evidence of peripheral nerve disease or compression

•Lhermitte phenomenon, an electric shock-like sensation in the neck radiating down the spine or into the arms, produced by forward flexion of the neck

•Imbalance not explained by rheumatoid involvement of the hips, knees, ankles, and feet

•Hand clumsiness and dropping objects not explained by rheumatoid hand involvement

●Physical findings relating to the spine, which are suggestive of atlantoaxial subluxation, include loss of cervical lordosis, scoliosis, resistance to passive spine motion, and abnormal protrusion of the anterior arch of the atlas felt by the examining finger on the posterior pharyngeal wall. Neurologic findings appropriate to the symptoms described above may be seen, including increased deep tendon reflexes (seen in myelopathy); extensor plantar responses; Hoffman sign; muscle weakness, spasticity, or muscle atrophy; gait disorders; and decreased deep tendon reflexes (seen in radiculopathy). (See 'Physical findings' above.)

●Routine imaging is not required for asymptomatic patients without neurologic findings unless they need to undergo a procedure or anesthetic that requires passive movement of the neck (see 'Imaging findings' above and 'Diagnosis and diagnostic evaluation' above). Patients with mild, nonspecific neck or occipital pain can be evaluated initially by conventional radiography with dynamic (flexion/extension) radiographs, but patients with evidence of subluxation or C1 to C2 synovitis require careful observation and magnetic resonance imaging (MRI) examination if symptoms or signs progress. Radiographic evaluation of the cervical spine is advised for all patients with RA scheduled to undergo surgery requiring manipulation of the neck for either anesthesia or surgery. (See 'Imaging findings' above and 'Diagnosis and diagnostic evaluation' above.)

●Atlantoaxial subluxation alone is not inexorably associated with neurologic dysfunction or with an increased risk of death. Although radiographic progression is common, it does not always correlate with neurologic deterioration. However, some patients with severe subluxation may be at risk for death. Patients with plain film radiographic evidence of cervical subluxation, with or without neurologic symptoms, have a five-year mortality rate of 17 percent. Patients with subluxation and signs of spinal cord compression have a poor prognosis without surgery. (See 'Prognosis' above.)

●Patients with instability but without signs of cord compression are at risk for severe injury and perhaps death due to a variety of insults. These include minor falls, whiplash injuries, and intubation. Such patients may benefit from rigid cervical collars. Surgery should be considered carefully and individualized for patients with subluxation but without signs or symptoms of cord compression. If surgery is not performed, patients should be followed on a regular basis with neurologic exams and repeat imaging and counseled about the warning signs of deterioration. Patients with subluxation and signs of spinal cord compression have a grave prognosis without surgical intervention to provide stability to the spine. (See 'Treatment' above and 'Medical therapy' above and 'Surgery' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledges Peter Schur, MD, who contributed to an earlier version of this topic review.