Version August 2024
INTRODUCTION — Active rheumatoid arthritis (RA) can destroy the cervical joints. This joint destruction may cause vertebral malalignment, including cervical subluxation (ie, a partial or incomplete dislocation of the vertebrae), which can be associated with pain, neurologic deficits, and deformity [1-3].
Improvements in the management of RA, including the availability of more effective therapies, have decreased the incidence of cervical subluxation. However, failure to recognize cervical subluxation may lead to irreversible consequences, such as respiratory compromise and paralysis.
The clinical manifestations and treatment of cervical 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, are discussed separately:
●(See "Clinical manifestations of rheumatoid arthritis".)
●(See "General principles and overview of management of rheumatoid arthritis in adults".)
●(See "Evaluation of the adult patient with neck pain".)
EPIDEMIOLOGY AND RISK FACTORS
Prevalence — Estimates of the prevalence of cervical subluxation among patients with rheumatoid arthritis (RA) range from 4 to 36 percent [4-12]. These estimates vary depending upon the study population, imaging techniques, degree of subluxation, and other factors.
Atlantoaxial instability accounts for approximately 65 percent of the total subluxations of the spine [13,14].
Experts in spinal surgery note that the rate of cervical subluxation among patients with RA has decreased with the advent of more effective disease-modifying antirheumatic drugs (DMARDs):
●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].
●In a study of patients with early RA who had been treated with a triple combination of conventional synthetic DMARDs, atlantoaxial and subaxial subluxation were each observed in 1.2 percent of patients [15].
●Another study of patients with early RA indicated that the prevalence of atlanto-axial subluxation after 12 years of follow-up was 4.6 percent. However, no patients in this study developed severe subluxation.
Risk factors — Numerous risk factors for the development of cervical subluxation have been identified [16-19].
In a 2017 systematic review and meta-analysis that limited its analysis to moderate- to high-quality studies, the following factors were associated with an increased risk of cervical spine instability [18]:
●Female sex
●Positive rheumatoid factor (RF)
●Long-term glucocorticoid use
●Long RA duration
●Erosive peripheral joint disease (in the hands or feet)
●Higher levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
Similarly, in individual studies, associations with cervical spine instability have been described with the following factors [11,16,17,19-21]:
●Higher disease activity scores
●Previous joint surgery
●Erosions in the hands, feet, hips, and knees
●Rapidly progressive erosive peripheral joint disease and joint space narrowing on hand radiographs [22]
●Early peripheral joint subluxations
●Osteoporosis
●Higher levels of anti-citrullinated protein antibodies (ACPA)
PATHOGENESIS
Pathogenesis of joint injury — Rheumatoid arthritis (RA) causes joint destruction by inducing synovitis in the affected joints. RA may cause cervical subluxation by inducing synovitis of the atlantoaxial, neurocentral (joints of Lushka), or facet joints (also known as apophyseal or zygapophyseal joints). All of these joints may be inflamed simultaneously. However, the degree to which each may play a role in the pathogenesis of cervical subluxation is not clear:
●Atlantoaxial joint synovitis – The atlantoaxial joint includes three separate synovial joints: two typical diarthrodial joints located laterally and one central joint made up of the odontoid (dens) and the posterior aspect of the anterior arch of the atlas.
•RA induces inflammation of the synovial tissue that lines these joints.
•Chronically active inflammation may result in joint destruction.
●Neurocentral joint synovitis – The neurocentral joints (ie, the joints of Luschka) permit flexion and extension of the cervical spine and limit lateral flexion.
•RA induces inflammation of the synovium that lines the neurocentral joints.
•This inflammation spreads to the adjacent intervertebral joints (which lack synovium and therefore cannot be directly affected by RA).
•Inflammation of the intervertebral joints may lead to cervical joint destruction [23]
●Facet joint synovitis – The facet joints (also known as apophyseal or zygapophyseal joints) provide stability to the cervical spine and prevent excessive movement that could damage the intervertebral discs.
•RA induces inflammation of the synovium of the apophyseal joints.
•This inflammation may lead to apophyseal joint destruction.
•Loss of the apophyseal joints causes vertebral malalignment and subluxation.
•This results in increased shear forces on the cervical spine.
•These shear forces induce microfractures of the vertebral endplates, disc herniation, and degeneration of disc cartilage, which further contributes to cervical instability [24].
Mechanisms of neurogenic injury — Neurologic findings may occur when the space available for the brain stem, spinal cord, or nerve roots is compromised by vertebral subluxation or synovial proliferation (ie, pannus formation) posterior to the odontoid. Joint destruction and/or spontaneous fusion often result in reduced range of motion.
The specific mechanism of neurologic injury varies with the anatomic subtype of subluxation:
●Atlantoaxial and occipitoatlantal disease – Among the joints of the cervical spine, the atlantoaxial joint is that which is most prone to subluxation. The atlas (C1) can sublux anteriorly, posteriorly, vertically, laterally, or rotationally, and all of these can cause cord injury [25]. However, anterior atlantoaxial subluxation is substantially more common than the other forms [26].
•Anterior subluxation – Abnormal anterior movement on the axis is the most common type of cervical subluxation (figure 1). It often results from laxity of the transverse ligament induced by proliferative C1 to C2 synovial tissue induced by active RA, but it may also occur as a result of erosion or fracture of the odontoid process (eg, dens, odontoid peg) [27]. Clinically, this causes the head to protrude forward.
•Vertical subluxation – Vertical movement in relation to the axis results from destruction of the lateral atlantoaxial joints or potentially from destruction of the occipitoatlantal joints.
Vertical atlantoaxial subluxation may occur following anterior or posterior subluxation.
As vertical subluxation progresses, the odontoid process penetrates the foramen magnum, and the odontoid may impinge upon the brainstem (figure 2) [28]. This process is known as "cranial settling" (or basilar invagination) and is associated with an increased risk of vertebrobasilar insufficiency and cranial nerve deficits. (See 'Nonurgent surgical evaluation' below.)
•Lateral subluxation – Lateral movement on the axis may be caused by asymmetric apophyseal joint erosion. Clinically, this may result in scoliosis and/or a head tilt.
•Posterior subluxation – Posterior movement on the axis can occur only if the odontoid process has been fractured/destroyed or if the C1 ring has been fractured. Clinically, this may cause the head to extend backwards.
●Subaxial disease – Instability of the subaxial (C3 to C7) joints, which may affect more than one level, occurs when there is synovitis of the facet joints with damage to the intervertebral discs and interspinous ligaments. This results in horizontal subluxation of one vertebral body upon another.
Clinically, subaxial disease may result in compression of the spinal cord, a cervical nerve root, or both [1]. Subaxial subluxation may also cause the head to protrude forward.
CLINICAL FEATURES
Neurologic manifestations — Cervical subluxation can result in a cervical radiculopathy, myelopathy, brainstem compression, and vertebrobasilar insufficiency.
Any rheumatoid arthritis (RA) patient who presents with a new sign or symptoms that suggests myelopathy, brainstem compression, or vertebrobasilar insufficiency requires immediate evaluation by a spine surgeon with experience evaluating and managing cervical spine instability. (See 'Immediate spine surgery evaluation' below.)
Clinical findings associated with these diagnoses include the following:
●Myelopathy – Cervical myelopathy may be associated with the following findings that may present suddenly, usually in relation to trauma. More often, these develop insidiously:
•Weakness in the arms, legs, or both
•Sensory loss and/or paresthesias in the arms or legs
•Urinary and/or rectal sphincter dysfunction
•Increased deep tendon reflexes
•Extensor plantar responses
•Hoffman sign
•Finger escape sign
•Muscle weakness, spasticity
•Gait disorders, including broad based gait, and difficulty with tandem gait
The Ranawat classification system grades the severity of cervical myelopathy as follows [29,30]:
•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
Cervical myelopathy, including physical examination findings, is discussed in detail elsewhere (see "Cervical spondylotic myelopathy", section on 'Clinical presentation'):
●Radiculopathy – Radiculopathy, which may occur in atlantoaxial or subaxial subluxation, produces weakness, sensory loss, and/or decreased deep tendon reflexes in one arm. The specific muscles and sensory areas affected depend on the specific nerve root that is impacted (table 1).
Compression of the greater (C2) or lesser (C1) occipital nerves may cause occipital neuralgia, and ear pain may be caused by compression of the greater auricular nerve, which derives from the C2 to C3 nerve roots.
Cervical radiculopathy is discussed in detail elsewhere. (See "Clinical features and diagnosis of cervical radiculopathy".)
●Vertebrobasilar insufficiency – Vertical subluxation of the odontoid process of C2 and C1 to C2 instability may cause vertebral artery compression, leading to vertebrobasilar insufficiency [1,31-33]. The compression can be complicated by in situ thrombus, arterial dissection, and/or rotational artery occlusion (bow hunter syndrome).
Vertebrobasilar insufficiency may be associated with the following findings:
•Dizziness
•Syncope
•Vertigo
•Bilateral leg weakness
•"Drop attacks" (ie, sudden weakness in the lower extremities)
•Diplopia and vision loss
•Oscillopsia (ie, a sensation that surroundings are in constant motion)
•Oropharyngeal dysfunction
Vertebrobasilar insufficiency is discussed in detail elsewhere. (See "Posterior circulation cerebrovascular syndromes".)
●Brainstem compression - Vertical subluxation of the odontoid process of C2 (figure 2) may cause compression of the lower brainstem leading to cranial nerve dysfunction, which may be associated with the following manifestations [29]:
•Loss of facial sensation, facial pain, or facial spasm (cranial nerve V)
•Tinnitus and vertigo (cranial nerve VIII)
•Dysphagia from compression of vagus and glossopharyngeal nerves (cranial nerve IX)
•Dysarthria from compression of hypoglossal nerve (cranial nerve XII)
Vertical subluxation of the odontoid process of C2 may also cause transient episodes of medullary dysfunction (such as respiratory irregularity). The frequency of sudden death due to medullary dysfunction is unknown [34,35].
Atlantoaxial subluxation is less likely to lead to brainstem compression but can be associated with cranial nerve V dysfunction.
The clinical manifestations of brainstem lesions are described in greater detail elsewhere. (See "Evaluation of the adult with acute weakness in the emergency department", section on 'Differential diagnosis of acute weakness'.)
Non-neurologic manifestations — Patients with cervical subluxation may not have non-neurologic manifestations. When present, these non-neurologic manifestations are nonspecific and may be subtle.
●Neck pain – A high level of suspicion for cervical subluxation in patients with RA is necessary because many may be asymptomatic. In one study from Finland of RA patients on the waiting list for orthopedic surgery, 59 of 154 (38 percent) had cervical subluxation. Neck pain was reported by 69 percent of those patients and by 65 percent of the 95 patients without subluxation [36].
The earliest and most common symptom of cervical subluxation is pain radiating towards the occiput [37]. Patients with active RA and cervical subluxation frequently complain of neck pain both with movement and at rest [38]. However, none of these symptoms are specific for cervical subluxation; patients often may have myelopathy without neck pain. The frequency of neck pain is variable; in one review, it is mentioned as occurring in 40 to 88 percent of patients [39].
Rarely, patients with cervical subluxation may also note a sensation of the head falling forward or "clunking" upon flexion of the cervical spine.
●Abnormal cervical spine curvature – Inspection of the cervical spine may demonstrate physical findings suggestive of cervical subluxation. The normal cervical spine demonstrates "cervical lordosis," meaning that the cervical spine curves anteriorly. Flattening of the cervical spine, cervical kyphosis, or other abnormal curvature of the cervical spine (ie, cervical scoliosis) may suggest cervical subluxation.
●Restricted passive range of motion – Patients with cervical subluxation may have restricted passive range of motion at the cervical spine. Normal range of motion for the cervical spine varies but is typically as follows:
•The cervical spine can rotate an average of 90 degrees (picture 1)
•The cervical spine can bend an average of 45 degrees laterally (picture 2)
-The cervical spine can forward flex to 60 degrees
-The cervical spine can extend backward 75 degrees
However, restricted passive range of motion of the cervical spine is nonspecific and may also be associated with cervical strain, cervical discogenic pain, cervical facet syndrome, and diffuse skeletal hyperostosis. Cervical spine range of motion (active or passive) should not be assessed in patients with severe pain, neurologic signs or symptoms, or a history of trauma.
Moreover, some patients with cervical subluxation will have normal, painless passive range of motion.
IMAGING TO ESTABLISH DIAGNOSIS IN SPECIFIC SCENARIOS — Imaging studies are central to diagnosing cervical subluxation (table 2). In addition to identifying the presence of subluxation, imaging is also used to identify neurologic complications and assess the stability of the spine.
Imaging leading to a diagnosis of cervical subluxation is typically obtained in one of the following scenarios:
●Asymptomatic patients undergoing preoperative evaluation
●Patients with symptoms suggestive of cervical myelopathy or nerve root impingement
●Patients with rheumatoid arthritis (RA) who present with persistent or recurrent neck or occipital pain
The selection of the appropriate imaging test is guided by the clinical presentation, especially if there is a history of trauma or neurologic compromise. Previously obtained imaging tests, if available, may also guide the selection of additional imaging studies. Imaging should be ordered in coordination with a spine surgeon as discussed in the sections that follow.
Following trauma
●Severe pain and/or neurologic signs or symptoms – These patients require urgent assessment with imaging in an emergency department because they may have a fracture or spinal instability. Spine precautions should be followed until the patient can be evaluated by a spine surgeon. (See "Cervical spinal column injuries in adults: Evaluation and initial management", section on 'Initial evaluation and management' and 'Spinal immobilization' below and 'Immediate spine surgery evaluation' below.)
●New-onset neck or occipital pain – Patients presenting with new-onset neck or occipital pain following trauma should undergo a sequential series of imaging, as outlined below (algorithm 1):
•Computed tomography of the cervical spine for all patients – Computed tomography (CT) of the cervical spine should be obtained first.
If a fracture or instability is identified, the patient should be immobilized immediately and transferred to an emergency department for urgent surgical evaluation. (See 'Spinal immobilization' below and 'Immediate spine surgery evaluation' below.)
We start with a CT of the cervical neck because CT is superior to magnetic resonance imaging (MRI) for identifying bony abnormalities, such as fracture, which may occur following trauma.
The posterior atlanto-dental interval (PADI) may be measured on CT or plain radiographs. The PADI is defined as the distance between posterior aspect of dens and anterior aspect of posterior arch of C1. PADI reflects the width of the spinal canal at C1-C2 level and typically measures between 19 and 27 mm. PADI <14 mm has been correlated with adverse surgical outcomes and is more associated with vertical subluxation (image 1) [40,41].
•Plain radiographs to assess subluxation – If fracture or instability is not identified on CT, plain radiographs with flexion and extension of the cervical spine should then be obtained to assess atlantoaxial subluxation.
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 a normal CT of the cervical neck, we obtain plain radiographs because CT (and MRI) may underestimate atlantoaxial subluxation when compared with flexion-extension plain film radiography [42]. Radiographs are taken with the patient sitting or standing; gravity pulls the head downwards when the neck is flexed, which reveals the maximal extent of atlantoaxial subluxation. CT and MRI are performed with the patient supine, making it difficult to attain an adequate degree of neck flexion to elicit the full extent of atlantoaxial subluxation.
•MRI for patients at high risk for cord compression – Risk factors for cord compression on CT or plain radiographs include (image 2) [43-45]:
-Separation between C1 and C2 (ie, anterior subluxation) >9 mm
-Space available for the (spinal) cord (ie, the distance between the posterior aspect of the dens and the anterior aspect of the posterior arch of the atlas) <13 mm
-Anterior atlantodental interval (ADI) >5 mm, which indicates clinically significant atlantoaxial instability (image 1) [46].
-Width of the subaxial central spinal canal (ie, C3 to C7) <14 mm [47].
-Cervical-medullary angle <135 degrees. The cervical-medullary angle is formed by a line drawn along the anterior aspect of the cervical-medullary cord and another line along the medulla. The normal angle is 135 to 175 degrees; angles less than 135 degrees indicate cranial settling [48].
Patients with any of these findings should undergo MRI to evaluate for evidence of possible cord compression or myelopathy. (See 'Possible cord compression or radiculopathy' below.)
●No pain or neurologic findings – Patients who have no neck or occipital pain following trauma, and have no new neurologic findings, do not require imaging of the cervical spine unless the patient is undergoing a procedure that requires a general anesthetic (algorithm 2). (See 'Persistent or recurrent occipital/neck pain or need for general anesthetic' below.)
Possible cord compression or radiculopathy — The symptoms associated with cord compression and radiculopathy are discussed above. (See 'Neurologic manifestations' above.)
Patients who present with signs or symptoms consistent with spinal cord compression should be immobilized immediately and transferred to an emergency department for urgent neurosurgical evaluation. (See 'Spinal immobilization' below and 'Immediate spine surgery evaluation' below.)
In patients who may have spinal cord compression or radiculopathy, our approach to imaging is as follows (algorithm 3):
●Non-contrast MRI for all patients – MRI is better than CT for visualization of the spinal cord and nerve roots (image 3) [49,50]. Myelopathy may present with high signal intensity in the spinal cord on T2-weighted images [51]. Gadolinium-containing contrast is generally necessary only when a tumor or infection is suspected.
●Add STIR sequences for neck/occipital pain – We add sagittal-plane short inversion tau recovery (STIR) sequences to a non-contrast MRI in patients who have neck or occipital pain or who have other reasons to assess cord compression. STIR can help identify inflammatory changes consistent with active RA (eg, inflamed synovium, bony erosions), which may help differentiate pain from cervical subluxation versus pain from active RA.
In addition, MRI with STIR is highly sensitive for detecting inflammatory changes (eg, bone marrow edema) that typically precede joint instability [52,53].
●Add contrast to assess synovitis – We use contrast-enhanced MRI if it is not clear whether the patient’s RA is in remission. Contrast-enhanced MRI helps both characterize and quantify the atlantoaxial pannus.
●CT myelography when MRI is not feasible – In patients unable to undergo MRI, CT myelography may be used to identify myelopathy caused by cord compression [54]. CT myelography requires the introduction of iodinated contrast subarachnoid space through lumbar puncture. CT myelography obtains images with a higher spatial resolution than typical MRI studies and can visualize the cerebrospinal fluid spaces and adjacent soft tissue in great detail, without being subject to metallic artifacts [55]. However, CT myelography is more invasive than MRI and requires exposure to both ionizing radiation and iodinated contrast.
●CT with contrast when CT myelography and MRI are not feasible – When CT myelography is not feasible, a CT scan with intravenous contrast may be able to visualize the surrounding soft tissues (eg, ligaments) enough to delineate the space available for the spinal cord. A CT scan with intravenous contrast can also detect inflammatory soft tissue proliferation from active rheumatoid arthritis, although MRI is superior at detecting both pannus and synovitis [49,50,56].
Possible brainstem compression — The symptoms associated with brainstem compression are discussed above (see 'Neurologic manifestations' above). Such patients should be immobilized immediately and transferred to an emergency department for urgent neurosurgical evaluation. (See 'Spinal immobilization' below and 'Immediate spine surgery evaluation' below.)
Our approach to imaging is as follows (algorithm 3):
●Non-contrast MRI for all patients – MRI is better than CT for visualization of the brainstem and cranial nerves (figure 1 and image 2).
Gadolinium-containing contrast is generally necessary only when a tumor or infection is suspected. In other cases, STIR images alone have been shown to be as sensitive and reliable for detecting inflammation as T1-weighted post-contrast MRI. Omitting the administration of contrast (when unnecessary) saves time and is associated with lower cost [57,58].
●CT with contrast when MRI is not feasible – When MRI is not feasible, a CT scan with intravenous iodinated contrast may provide evidence of subluxation and/or inflammatory soft tissue proliferation from active RA.
Possible vertebrobasilar insufficiency — The symptoms associated with vertebrobasilar insufficiency are discussed above. (See 'Neurologic manifestations' above.)
Patients presenting with vertebrobasilar insufficiency require urgent evaluation by a vascular neurologist.
In patients who may have vertebrobasilar insufficiency, we suggest two separate studies (algorithm 3):
●MRI of the cervical spine – The MRI should be non-contrast and fat saturated. Fat-saturated MRI suppresses the signal from the normal adipose tissue that surrounds the vertebral artery, and it enhances the ability of MRI to detect intramural hematoma consistent with arterial dissection [59]. Other considerations regarding the use of MRI for the evaluation of cervical subluxation are described in the table (table 2).
Synovitis, as proposed by the OMERACT (Outcome Measures in Rheumatology) group, is defined as thickening of the synovial membrane at the atlantoaxial joint and demonstrates hyperintensity on STIR sequences or abnormal contrast enhancement on T1-weighted MRI. However, it should be noted that STIR images alone have been shown to be as sensitive and reliable for detecting inflammation as T1-weighted post-contrast MRI. Some argue that omitting the administration of contrast saves time and is associated with lower cost [57,58].
●Angiography of the posterior circulation – The choice of modality for angiography (ie, CT, MR, conventional) depends on local expertise. Dynamic cervical angiography, which is performed with a rotated neck to identify dynamic compromise of the vertebral arteries, is best performed with conventional angiography. Otherwise, noninvasive modalities are adequate to evaluate the posterior circulation.
Persistent or recurrent occipital/neck pain or need for general anesthetic — We obtain a series of cervical spine plain radiographs for all patients who need to receive a general anesthetic, regardless of how long the patient has had RA or the extent of their disease. Subluxation is not always symptomatic, and in a patient with undiagnosed cervical subluxation, neck positioning required for intubation may cause paralysis or death [36].
We also obtain a series of cervical spine plain radiographs for patients with RA who have persistent or recurrent occipital/neck pain, given the potential risks associated with undiagnosed cervical subluxation.
The use of plain radiographs to evaluate cervical subluxation is summarized in the table (table 2).
Asymptomatic patients — Patients with RA who have no signs or symptoms of cervical subluxation, and no history of trauma affecting the neck, do not require imaging studies unless the patient is undergoing a procedure that requires a general anesthetic (algorithm 2). (See 'Persistent or recurrent occipital/neck pain or need for general anesthetic' above.)
DIFFERENTIAL DIAGNOSIS — Rheumatoid arthritis (RA) patients may present with vertebrobasilar insufficiency, myelopathy, radiculopathy, or neck pain that is unrelated to cervical subluxation.
Given the potential for serious, permanent neurologic morbidity, the possibility of cervical subluxation should always be investigated. However, the presence of one of these syndromes in a patient without radiographic evidence of cervical subluxation should prompt an evaluation for alternate causes.
●Cervical myelopathy – The symptoms associated with cervical myelopathy are discussed above. (See 'Non-neurologic manifestations' above.)
The differential diagnosis of cervical myelopathy is extensive and includes cervical disc herniation, cervical osteophytes, and ossification of the posterior longitudinal ligament and ligamentum flavum. (See "Disorders affecting the spinal cord".)
The evaluation of cervical myelopathy is discussed elsewhere. (See "Cervical spondylotic myelopathy", section on 'Diagnosis' and "Anatomy and localization of spinal cord disorders", section on 'Evaluation'.)
●Cervical radiculopathy – The symptoms associated with cervical radiculopathy are discussed above. (See 'Non-neurologic manifestations' above.)
In addition to cervical subluxation, other causes of cervical radiculopathy include cervical disc herniation and multiple infectious or inflammatory diagnoses (table 3).
The evaluation of cervical radiculopathy is discussed elsewhere. (See "Clinical features and diagnosis of cervical radiculopathy", section on 'Diagnostic evaluation'.)
●Brainstem compression – The symptoms associated with brainstem compression are discussed above. (See 'Possible brainstem compression' above.)
Cervical subluxation is an uncommon cause of brainstem compression. Acute brainstem compression (ie, developing over minutes to hours) may be caused by trauma and hematoma [60]. Subacute brainstem compression (ie, developing over days to weeks) may be caused by neoplasm, abscess, and (rarely) vertebral artery abnormalities [61,62].
●Vertebrobasilar insufficiency – The symptoms associated with vertebrobasilar insufficiency are discussed above. (See 'Non-neurologic manifestations' above.)
Cervical subluxation is an uncommon cause of vertebrobasilar insufficiency. More common causes of vertebrobasilar insufficiency are atherosclerosis, cardiogenic embolism, and vascular dissection.
The evaluation of vertebrobasilar insufficiency is discussed elsewhere. (See "Posterior circulation cerebrovascular syndromes", section on 'Extracranial vertebral arteries'.)
●Neck pain – It is not always possible to reliably determine the cause of neck pain. Therefore, the evaluation should focus on excluding serious conditions that require intervention.
In an RA patient with neck pain, the presence of a "red flag" listed in the table (table 4), including recent trauma, should prompt an urgent evaluation (algorithm 4).
Neck pain may also be a feature of vertebrobasilar insufficiency, cervical radiculopathy, and cervical myelopathy.
After these diagnoses have been excluded, differentiating among various musculoskeletal conditions (eg, cervical strain, cervical discogenic pain, cervical facet osteoarthritis, myofascial pain syndrome) is less critical, particularly if symptoms resolve with symptomatic management.
The evaluation of neck pain is discussed elsewhere. (See "Evaluation of the adult patient with neck pain", section on 'Evaluation'.)
MANAGEMENT
Indications for surgery — The definitive treatment of cervical subluxation is surgical stabilization of the cervical spine. Medical therapy may help slow disease progression but cannot reverse cervical subluxation.
The timing of surgery depends largely upon the presence or absence of signs of spinal cord compression and the degree of spinal instability or hypermobility [29].
In patients with minimal symptoms and no evidence of instability, spinal stenosis or brainstem compromise may not progress and can be monitored clinically in lieu of surgery. (See 'Patients without risk factors' below.)
However, in patients with evidence of neurologic compromise, surgery may prevent both morbidity and mortality. (See 'Patients with cord/brainstem compression, vertebrobasilar insufficiency, or cervical spine instability' below.)
Preoperative considerations
Spinal immobilization — Spinal immobilization should take place in consultation with a spine surgeon experienced in the management of cervical subluxation.
●Hard collar for most patients – For patients with cervical spine instability who are awaiting surgery, we suggest immobilization with a hard collar to diminish neck pain and to prevent repeated spinal cord irritation with neck flexion. Whether the hard collar should be used continuously is determined by the spine surgeon, based on the degree on instability, neurologic findings, and patient adherence.
A hard collar likely provides more protection of the neural structures than a soft collar. In one study of 50 rheumatoid arthritis (RA) patients with unstable atlantoaxial subluxation, a stiff cervical collar radiographically stabilized atlantoaxial subluxation in over 50 percent of patients [63]. However, these findings have not been replicated by all studies [64]. Also, there is no evidence that hard collars prevent progression of cervical subluxation.
●Halo for severe instability – A halo brace is the most rigid form of external fixation of the upper cervical spine. A ring ("halo") is affixed to the skull and attached to a vest that fits around the chest. External halo fixation is occasionally required in severe cases of instability or fracture, or in patients with vertical subluxation. Halos are generally used only in cases of severe instability because of the risk of serious and sometimes life-threatening complications. When a halo is required, it is rare to use it for more than 6 to 12 weeks due to problems with pin-site infection and loosening.
External halo fixation causes a 10 to 30 percent reduction in forced vital capacity due to restriction of chest wall expansion [65]. Therefore, halos are associated with a high rate of complications among those with preexisting pulmonary disease.
Halo fixation is also associated with a high rate of complications among older adults. In a retrospective study of 22 older adult patients who underwent placement of a halo device, there were 31 complications (including respiratory compromise, pin-related issues, dysphagia, and death) [66]. However, the high rate of complications may be due to a high rate of comorbid conditions (eg, pulmonary disease) among older adults.
●Soft collars provide little support – Soft collars are more comfortable for the patient but provide little structural support. Soft collars may help remind the patient to restrict certain activities that may be detrimental and may be used when a hard collar is contraindicated (ie. risk of pressure sores) or not feasible due to poor patient compliance.
Preoperative imaging — We evaluate all patients undergoing surgery for cervical subluxation with both a CT and MRI [46].
CT can demonstrate bony anomalies that may not be apparent on plain films or MRI. A 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 [67]. Thus, CT can help determine the best surgical technique to be used, including the type, size, and trajectory of implants.
However, MRI is better at visualizing soft tissue, including abnormalities affecting the brainstem, spinal cord, nerve roots, ligaments, and discs. When deciding whether to pursue surgery, MRI may be useful to demonstrate evidence of early instability or myelopathy, which may require surgical intervention.
The role of CT and MRI in the evaluation of patients with cervical subluxation is summarized in the table (table 2).
Other considerations
●Home safety – 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.
●No spinal manipulation – Spinal manipulation is contraindicated in patients with cervical spine instability.
●Pain management – Patients who have pain due to irritation of C2 nerve root 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 also obtain some benefit from local nerve blocks, although the relief is generally temporary.
●Traction – Traction in patients with cervical subluxation is controversial. However, it 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.
●Anesthesia considerations – When anesthesia is indicated for any procedure, stability of the cervical spine should be assessed radiographically, if feasible.
If cervical spine instability is present or the question has not been resolved prior to the procedure, we consider video laryngoscopy to avoid neck manipulation.
●Multidisciplinary care – Close coordination between surgeon, rheumatologist, and other medical care providers is essential to assure timely intervention and to decrease complications. Perioperative considerations for patients with rheumatic disease are discussed elsewhere. (See "Preoperative evaluation and perioperative management of patients with rheumatic diseases".)
Patients with cord/brainstem compression, vertebrobasilar insufficiency, or cervical spine instability
Immediate spine surgery evaluation — Any patient with RA who is suspected of having cervical subluxation with evidence of cord compression, brainstem compression, vertebrobasilar insufficiency, or cervical spine instability requires immediate surgical evaluation. Imaging should be ordered in coordination with a spine surgeon experienced in the management of cervical spine instability. Signs and symptoms associated with these complications, and the imaging of these complications, are discussed above. (See 'Neurologic manifestations' above and 'Imaging to establish diagnosis in specific scenarios' above.)
The timing of surgery must be individualized based upon the severity of the findings and the patient's general health. However, surgery should be considered before the degree of neurologic impairment or stenosis become severe. alone analysis showed that the prognosis for neurological recovery after surgery was predicted based on the severity of the preoperative deficit [45]. The posterior atlanto-dental interval (PADI) was the most useful predictor of neurologic recovery after surgery. Patients with atlantoaxial instability and a PADI of <10 mm had no recovery, whereas when the PADI was >10mm, at least one Ranawat class of recovery always occurred. There are no randomized trials comparing surgical intervention with observation.
Left untreated, atlantoaxial instability can lead to poor clinical outcomes, morbidity, and possibly even death. In a case series of 21 patients with RA who declined surgery, no patient demonstrated spontaneous improvement. In addition, 16 (76 percent) showed deterioration at follow-up. Interestingly, the probability of survival at seven years was 0 percent following the onset of myelopathy [20]. This underscores the importance of timely treatment. In addition, it is postulated that untreated atlantoaxial instability can result in upward migration of the dens and cervical spine due to the incompetence of the C1 lateral masses and decreased distance between the odontoid process and cranial cavity [2,44].
Prophylactic atlantoaxial fusion may prevent vertical subluxation. In one case series, 20 patients with RA were treated with atlantoaxial fusion for atlantoaxial instability on the basis of unsuccessful adequate conservative treatment. After five years of follow-up, no patient had progressed to vertical cranial migration [29,45].
Surgical options and outcomes — Surgical evaluation and operative procedures should be performed by a surgeon with expertise in the management of cervical spine instability, given their complexity [29].
●Fusion – For most patients, C1 is fused to C2 using a posterior approach. C1 to C2 fusion is generally adequate to prevent further vertical subluxation.
Occipitocervical fusion (ie, fusion of the occiput through to C2 or C3) may be required in patients with severe deformity and/or cranial settling with brainstem compression. Occipitocervical fusions are associated with more complications, including an increased risk of subaxial subluxation (compared with patients who undergo C1 to C2 fusions).
Fusion of the entire cervical and upper thoracic spine may be required in patients with subaxial subluxation. This is especially true for patients with active RA despite appropriate treatment with disease-modifying antirheumatic drugs (DMARDs). Fusion of the cervical to the thoracic spine in patients with subaxial subluxation may prevent subluxation of additional spinal levels.
●Decompression – Spinal decompression refers to surgical intervention designed to reduce pressure on the spinal cord or its roots. Decompression is indicated for cervical stenosis unless it is mild and asymptomatic. Decompression can sometimes be accomplished indirectly by realigning and fusing the spine. Only rarely would decompression without a fusion be considered (ie, C1 laminectomy alone may be reasonable in a case of stenosis and neurologic impairment from atlanto-axial subluxation with spontaneous fusion in the subluxed position). Occasionally, gentle traction may be used in an awake patient to provide indirect decompression as a temporizing measure while preparing for the definitive operation.
Patients with cervical spine subluxation and signs of spinal cord compression have a grave prognosis without surgical intervention to stabilize the spine [31,68].
●Improved survival with surgery – In patients with myelopathy due to atlantoaxial subluxation, surgery is associated with improved survival. A 2003 observational study compared 19 patients with RA who had symptomatic atlantoaxial subluxation who underwent laminectomy and occipitocervical fusion with 21 others who were managed conservatively [69]. The 5- and 10-year survival rates for those who underwent surgery were 84 and 37 percent, respectively. By contrast, none of the 21 patients managed conservatively survived longer than eight years.
The prognosis for RA patients who undergo surgery appears to be improving in part, due to earlier referral, enhanced technique, and better perioperative management [70-72]. An analysis of 224 RA patients managed surgically over 30 years (between 1981 and 2011) demonstrated an overall improvement in survival between the first and last decades (35 versus 55 percent 10-year survival).
●Improvements in neurologic outcomes – In patients with myelopathy due to cervical subluxation, surgery may improve the myelopathy and/or slow neurologic progression in some patients [45]. Postoperative outcomes after cervical spine surgery among RA patients were variable. Improvement in Ranawat scale by a least one class was noted from 0 to 54 percent of cases. This is consistent with published reports stating that patients typically improve by one class after undergoing cervical spine fusion [39,73,74].
●Patient-reported outcomes – Excellent results were reported in a retrospective analysis of prospectively collected data of 126 patients undergoing C1 to C2 fusions [75]. Twenty (16 percent) of the patients had surgery for rheumatoid disease and the results were comparable to patients undergoing surgery for osteoarthritis and better than those treated for trauma (in terms of how much the patients perceived the operation helped). Outcomes were assessed using the Core Outcome Measures Index (COMI) for the neck. This instrument is a validated, multidimensional outcome tool. The questionnaire was completed at multiple timepoints, with 94 percent completing the questionnaire at the two-year timepoint. Seventy-five percent of patients in the entire cohort achieved the Minimal Clinically Important Change (≥2.2 points out of 10) from preoperation to two years postoperation. Mean COMI scores for the entire cohort reduced significantly from baseline to two years postoperation: 6.9 ± 2.4 to 2.7 ± 2.5 (p<0.0001), and the reduction in COMI score did not differ significantly between the diagnostic categories (p = 0.27). Of the patients with RA, 94.7 percent were satisfied with their care, 89.5 percent felt that the operation helped a lot, and 78.9 percent were satisfied or very satisfied to spend the rest of their lives with the current symptoms.
Patients with intractable pain or with asymptomatic spinal stenosis
Nonurgent surgical evaluation — Nonurgent surgical evaluation is indicated for RA patients who present with intractable neck/occipital pain or asymptomatic spinal stenosis.
●Intractable neck/occipital pain – We refer patients with intractable neck pain or occipital neuralgia (without neurologic deficits) for imaging and nonurgent surgical evaluation. (See 'Persistent or recurrent occipital/neck pain or need for general anesthetic' above.)
●Asymptomatic spinal stenosis – Imaging of the cervical spine is sometimes obtained while evaluating issues other than cervical subluxation. We refer asymptomatic patients for nonurgent surgical evaluation when any of the following imaging findings are present:
•Minor spinal stenosis without symptoms
-PADI <14 mm at any level on plain radiographs
-Spinal cord <13 mm on MRI or CT
•Cranial settling
•Hypermobility on flexion/extension films at a relatively stenotic segment
•Signal change in the cord on MRI
The degree of C1 to C2 subluxation may be reported as either the PADI or the atlantodental interval (ADI) (image 4). The PADI is a direct measurement of the spinal cord and is a better predictor of paralysis than the ADI. The ADI is an indirect measurement of the spinal cord and is a less reliable indicator of the size of the spinal canal due to variability in the diameter of the atlas [45].
Serial imaging demonstrating that the ADI has decreased over time may create a false sense of security. However, it indicates greater risk of neurologic compromise due to the onset of cranial settling from destruction of the atlantoaxial joints [73]. The diameter of the lower portion of the odontoid is greater than that of the upper aspect. As C1 settles on C2 (higher Clark station), the ADI may become smaller (figure 3). This should prompt an MRI to assess the degree of cranial settling and brainstem compression. (See 'Mechanisms of neurogenic injury' above.)
Surgical options and rationale — Surgical options for patients with intractable neck pain, occipital neuralgia, or asymptomatic spinal stenosis are the same as those for patients with more serious neurologic manifestations. These options are described above. (See 'Surgical options and outcomes' above.)
If a patient elects not to pursue surgery, we follow the patient clinically, as described below. (See 'Patients without risk factors' below.)
Surgery should be considered carefully and on an individualized basis for patients with subluxation but without signs or symptoms of cord compression. Operative stabilization may provide symptomatic relief from intractable neck or occipital pain. However, it is not clear whether surgical intervention is required to prevent disease progression.
Neurologic deterioration is not common in asymptomatic or minimally symptomatic patients. In a series of 752 patients with RA, patients who were asymptomatic or presented only with hyperreflexia or dysesthesia (ie, Ranawat I and II) only rarely experienced deterioration of their neurologic status and did not benefit from surgery [68].
However, some data support the hypothesis that early C1 to C2 fusion for atlantoaxial subluxation, before the development of significant superior migration of the odontoid (ie, cranial settling, vertical subluxation, or basilar invagination), decreases the risk of further progression of cervical spine instability. A retrospective study of 110 RA patients who underwent cervical spine fusion noted that patients who underwent prophylactic C1 to C2 fusion for atlantoaxial subluxation were less likely to develop cervical instability than patients who underwent occiput to C3 fusion following superior migration of the odontoid [76]:
A limiting factor is that the incidence of sustained neurologic deterioration related to surgery may be as high as 6 percent [77]. As a result, a skilled surgical team and careful preoperative assessment of each patient are important elements of any surgical plan.
Patients without risk factors — We follow patients clinically, without surgical intervention, if the following criteria are met:
●The evaluation does not suggest cord compression, brainstem compression, or vertebrobasilar insufficiency
●The patient does not have intractable neck or occipital pain
●Imaging does not demonstrate cervical spine instability
●The spinal canal is minimally reduced (ie, PADI >14 mm on plain radiographs or spinal cord >13 mm on MRI at all levels)
For example, a patient with tolerable pain or occipital neuralgia due to minor cervical subluxation, but without evidence of cord compression, cervical spine instability, or spinal stenosis, could be followed clinically.
We reevaluate such patients every 6 to 12 months. New imaging is obtained if clinically indicated (ie, neurologic findings or increasing pain). The frequency of evaluations may be reduced if the examination remains stable after the first year of follow-up.
A soft cervical collar may be used to help manage pain. However, there is no evidence that immobilization prevents instability or neurologic risk secondary to trauma, and it may lead to weakened neck muscles.
Patients for whom surgery is indicated but who cannot tolerate an operation because of their medical condition, or who choose nonoperative treatment, must be followed carefully. A hard or soft collar may be used as needed for symptomatic care. Until more data are available, we do not recommend that RA patients with cervical instability perform cervical strengthening exercises. One small study found that isometric neck extensor muscle tightening worsened radiographically apparent atlantoaxial subluxation in patients with cervical instability [78].
All RA patients with cervical spine involvement should be assessed for fall risk and advised to avoid activities that may place them at greater risk for falls or for head or neck trauma, including spine manipulation.
PREVENTION — In patients with rheumatoid arthritis (RA) who lack cervical subluxation, optimizing RA treatment with disease-modifying antirheumatic drugs (DMARDs) may help to prevent or substantially delay the onset of cervical subluxation. (See "General principles and overview of management of rheumatoid arthritis in adults".)
Limited evidence suggests that the early use of intensive medical treatment, particularly with biologic DMARDs, may help to prevent the development of cervical spine subluxation [15,79-81]. These studies support the approach of employing early aggressive treatment for RA to achieve disease control reduces the subsequent development of cervical instability. However, once cervical spine involvement occurs, medical therapy may not improve the prognosis [80,82].
However, even with early and aggressive DMARD treatment, cervical subluxation may still occur in patients with persistently active RA. In a study of 272 patients who were enrolled in a clinical trial designed to tightly control RA disease activity, 7 percent developed significant atlantoaxial subluxation over 10 years of follow-up [83].
PROGNOSIS
●Mortality – Cervical subluxation is not a common cause of death among patients with rheumatoid arthritis (RA). In a prospective study of 46 patients with cervical subluxation due to RA, 21 patients died during follow-up [84]. None of the deaths were attributed to cervical subluxation. Patients with evidence of cervical subluxation on plain radiographs, regardless of the presence of neurologic symptoms, have a five-year mortality rate of 17 percent [28].
Deaths due to cervical subluxation are generally caused by cord or brainstem compression. In one series of 104 consecutive autopsies of patients with RA, 11 cases of severe cervical subluxation were found [35]. In all 11 patients, the odontoid protruded posterosuperiorly and impinged on the medulla within the foramen magnum. In five patients, spinal cord compression was determined to be the only cause of death.
●Morbidity – Atlantoaxial subluxation alone is not always associated with neurologic dysfunction [84]. Although radiographic progression is common, it does not always correlate with neurologic deterioration [37,85-88].
Patients with severe cervical subluxation are at risk for severe injury due to a variety of insults (eg, minor falls, whiplash, intubation), even if they are asymptomatic.
The inability to walk preoperatively confers a poor prognosis for recovery after surgical intervention. In one study, only 20 percent of patients with atlantoaxial subluxation who were not ambulatory at the time of surgery improved after treatment [89].
All forms of cervical subluxation have the potential to impact the spinal cord. However, in general, vertical subluxation (cranial settling) is associated with a worse prognosis than anterior or lateral subluxation. Vertical subluxation may lead to medullary dysfunction and/or vertebrobasilar insufficiency [90].
●Impact of inflammatory arthritis on prognosis – Appendicular joint inflammation increases the risk of falling and limits postoperative mobility and self-care, and complicates rehabilitation.
The immunosuppressive effects of glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs increase the risk of infection and may impair wound healing.
Glucocorticoid treatment increases the risk of osteoporosis, which in turn may lead to a higher rate of pseudarthrosis and potential for fracture.
SUMMARY AND RECOMMENDATIONS
●Epidemiology and risk factors – Estimates of the prevalence of cervical involvement among patients with rheumatoid arthritis (RA) vary widely; since the introduction of biologic disease-modifying antirheumatic drugs (DMARDs), fewer RA patients appear to have required surgery than before.
Risk factors for cervical subluxation include longer disease duration and high disease activity. (See 'Epidemiology and risk factors' above.)
●Clinical manifestations – Cervical subluxation may present with cervical myelopathy, radiculopathy, vertebrobasilar insufficiency, or brainstem compression (see 'Neurologic manifestations' above):
The earliest and most common symptom of cervical subluxation is pain radiating superiorly toward the occiput. Patients may also demonstrate loss of normal cervical lordosis or restricted passive range of motion. These findings are not specific for cervical subluxation. (See 'Non-neurologic manifestations' above.)
●Imaging evaluation – The evaluation depends on the patient's symptoms and whether the patient presents in the setting of trauma.
•Patients with RA who have severe pain and/or neurologic signs or symptoms following trauma require immobilization and urgent surgical evaluation prior to imaging (algorithm 1). (See 'Following trauma' above.)
•Patients with RA who have new neck or occipital pain following trauma should undergo CT of the cervical spine to look for evidence of instability or fracture (algorithm 1). (See 'Following trauma' above.)
•Patients with RA who present with suspicion of cord or brainstem compression, radiculopathy, or vertebrobasilar insufficiency should be evaluated with a non-contrast MRI (algorithm 3). (See 'Possible cord compression or radiculopathy' above.)
•Routine imaging is not required for asymptomatic patients without neurologic findings unless they need to undergo a procedure or be administered an anesthetic that requires passive movement of the neck (algorithm 2). (See 'Asymptomatic patients' above.)
•For patients with RA who require general anesthesia or have persistent or recurrent neck/occipital pain, we obtain a series of plain radiographs of the cervical spine. 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 (algorithm 2). (See 'Persistent or recurrent occipital/neck pain or need for general anesthetic' above.)
●Differential diagnoses – In a patient with RA, cervical subluxation is an important initial consideration among patients who present with vertebrobasilar insufficiency, cervical radiculopathy, cervical myelopathy, or neck pain. However, other causes are more common and should be considered after cervical subluxation has been excluded. (See 'Differential diagnosis' above.)
●Treatment approach
•Preoperative considerations – Most RA patients awaiting surgery for cervical subluxation (and all patients with cervical spine instability) should receive a hard collar, which may diminish the symptoms associated with cervical subluxation and reduce the risk of neurologic morbidity.
Before surgery, we evaluate most patients with both CT and MRI. A CT scan is generally used to plan the surgical approach, while an MRI is better at evaluating soft tissues, such as the brainstem and spinal cord.
Patients should avoid cervical spine manipulation of the spine and have their home environment evaluated to minimize the risk of falls. (See 'Preoperative considerations' above.)
•Urgent surgical indications – Patients with RA who have progressive myelopathy, brainstem compression, vertebrobasilar insufficiency, or cervical spine instability require urgent surgical evaluation. (See 'Patients with cord/brainstem compression, vertebrobasilar insufficiency, or cervical spine instability' above.)
•Patients with intractable neck/occipital pain or asymptomatic spinal stenosis – Patients with RA who have intractable neck/occipital pain or asymptomatic spinal stenosis should receive a nonurgent surgical evaluation. (See 'Patients with intractable pain or with asymptomatic spinal stenosis' above.).
•Minor cervical subluxation without risk factors – For patients with RA who lack specific risk factors (ie, no clinical evidence of cord/brainstem compression or vertebrobasilar insufficiency, no radiographic evidence of cervical instability, no intractable neck/occipital pain, minimal spinal stenosis), we follow the patient clinically (initially in six months to one year, and then less frequently if follow-up examinations are stable). (See 'Patients without risk factors' above.)
●Surgical options – For most patients, C1 is fused to C2 using a posterior approach. Occipitocervical fusion (ie, fusion of the occiput through to C2 or C3) may be required for patients with severe deformity and/or cranial settling with brainstem compression. Fusion of the entire cervical and upper thoracic spine may be required for patients with subaxial subluxation.
ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledges Peter Schur, MD, who contributed to an earlier version of this topic review.
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