Cervical Subluxation in Rheumatoid Arthritis

7/26/2019 Cervical Subluxation in Rheumatoid Arthritis

1/14

Official reprint from UpToDate2016 UpToDate

AuthorsPeter H Schur, MDBradford L Currier, MD

Section EditorRavinder N Maini, BA, MB BChir,FRCP, FMedSci, FRS

Deputy EditorPaul L Romain, MD

Cervical subluxation in rheumatoid arthritis

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: May 2016. | This topic last updated: Feb 25, 2016.

INTRODUCTION The discovertebral joints in the cervical spine may be affected in patients with rheumatoid arthritis

(RA) with resulting osteochondral destruction [1,2]. A review of the clinical manifestations and treatment of atlantoaxial

(C1 to C2) and subaxial subluxation in RA is 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 of

management of rheumatoid arthritis in adults" and "Evaluation of the patient with neck pain and cervical spine disorders" .)

CERVICAL INVOLVEMENT Cervical joint destruction in patients with rheumatoid arthritis (RA) may lead to vertebral

malalignment (eg, subluxation), causing pain, neurological deficit, and deformity. Risk factors for development of cervical

subluxation include older age at onset of RA, more active synovitis, higher levels of C-reactive protein, rapidly progressive

erosive peripheral joint disease, and early peripheral joint subluxations [3,4]. Both atlantoaxial and subaxial (below C2)joints may be involved.

Atlantoaxial disease Among the joints of the cervical spine, the atlantoaxial joint is prone to subluxation in multiple

directions, potentially leading to cervical myelopathy [5]. The atlas (C1) can move anteriorly, posteriorly, vertically, laterally,

or rotationally relative to the axis (odontoid and body of C2):

Pathogenesis There are two possible mechanisms for involvement of the intervertebral joints in the cervical spine in

RA:

Bursal spaces exist between the cervical interspinous processes. In some rheumatoid patients, bursal proliferation has led

to radiographically demonstrated destruction of the spinous processes [10].

The involvement and severity of cervical spine disease in RA parallels the progression of peripheral joint erosions. As a

result, cervical subluxation is more likely in those with erosions of the hands, feet, hips, and/or knees [ 11,12].

Neurological findings may occur when the space available for the brain stem, spinal cord, or nerve roots is compromised

by vertebral subluxation.

Abnormal anterior movement on the axis is the most common type of subluxation. I t 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 [6].

Posterior movement on the axis can occur only if the odontoid peg has been fractured from the axis or has been

destroyed.

Vertical movement in relation to the axis is least common it results from destruction of the lateral atlantoaxial joints

or of bone around the foramen magnum [7].

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 [8].

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 [9]. This may produce microfractures of the vertebral endplates, disc herniation, and degeneration of

disc cartilage.


2/14

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.

Prevalence Although decreases in rates of hospitalizations for certain manifestations of severe RA (eg, rheumatoid

vasculitis, splenectomy for Feltys syndrome) were recorded in California, no significant decrease in rates of

hospitalization for cervical spine surgery was noted from 1983 to 2001 [ 13]. However, the clinical experience of experts in

spinal surgery is that the rate of occipital-cervical fusion has decreased with the advent of more effective disease-

modifying antirheumatic drugs (DMARDs). The prevalence of cervical involvement among those with RA varies with the

patient subset studied.

An increased risk of radiographic cervical spine involvement has been associated with the presence in serum of

rheumatoid factor and with an elevated C-reactive protein level, but has not been associated with the presence of human

leukocyte antigen (HLA)-DR4 [4,17].

Symptoms 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 towards the occiput [18]. Additional symptoms of subluxation include:

Neurologic findings in patients with atlantoaxial subluxation may also include 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.

Neurologic signs and symptoms often have little relationship to the size of the abnormally widened space between the

arch of the atlas and the anterior aspect of the dens (anterior atlantodental interval [AADI]) or to the amount of subluxation

between subaxial vertebrae. The magnitude of the space available for the cord (SAC) in the subaxial spine or at C1 to C2,where it is known as the posterior atlantodental interval (PADI), does correlate with the incidence of neurological

compromise [20]. The symptoms of spinal cord compression that demand immediate attention and intervention include

[21]:

In one series of 113 patients with RA referred for hip or knee arthroplasty, 61 percent had roentgenographic evidence

of cervical spine instability [12].

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) documented anterior atlantoaxial subluxation and vertical subluxation in 23 and 26 percent,

respectively [14]. None of these patients required surgical procedures on the cervical spine.

In a group of 476 hospitalized patients with RA, vertical subluxation was noted in 4 percent [ 15].

In a group of 165 Greek patients in an outpatient setting, with mean age of 60 years and duration of disease of 12

years, the prevalence of atlantoaxial subluxation of 2.5 mm on lateral radiograph was 21 percent, but neurologic

impairment was only present in one patient [16]. Subaxial subluxation 1 mm at one or more levels was present in 44percent.

Spastic quadriparesis is slowly progressive.

Sensory findings are also common, including painless sensory loss in the hands or feet.

In patients with C1 to C2 subluxation, transient episodes of medullary dysfunction (such as respiratory irregularity)

were associated with vertical penetration of the odontoid process of C2 and with probable vertebral artery

compression [19]. Sudden death may occur. The rate, reported as 10 to 20 percent in the older literature, is

uncertain.

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


3/14

However, instead of compression of the spinal cord, some of these symptoms may be due to compression of the vertebral

arteries, which must wind through foramina within the lateral aspects of C1 and C2. Findings on magnetic resonance

imaging (MRI) may help distinguish between these two possibilities.

Physical findings Physical findings relating to the spine which are suggestive of atlantoaxial subluxation include:

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

IMAGING FINDINGS Patients with mild, nonspecific neck or occipital pain can be evaluated initially by conventional

radiography, but patients with evidence of subluxation or of C1 to C2 synovitis require careful observation and magnetic

resonance imaging (MRI) examination if symptoms or signs progress. The use of conventional radiographs, computerized

tomography (CT), and MRI are discussed below. (See 'Symptoms' above and 'Physical findings' above and 'Conventional

radiography'below and 'CT scan' below and 'Magnetic resonance imaging'below.)

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 3 mm of separation between the

odontoid peg and the C1 arch (image 1) [19,22]. 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

[20,23,24]. In addition, if the space available for the spinal cord is less than 13 mm anywhere in the cervical region, there

is an increased risk for neurologic impairment. In symptomatic patients, the films in flexion should be taken only after

radiographs (including an open-mouth view) have excluded an odontoid fracture or severe atlantoaxial subluxation.

These structures may be difficult to visualize effectively 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. In addition, the usual landmarks may be obliterated in advanced disease [ 25].

Since neck positioning required for intubation prior to surgery may be fatal among patients with rheumatoid arthritis (RA)

and unrecognized C1 to C2 disease, and since subluxation is not always symptomatic, 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 [26].

CT scan CT can demonstrate spinal cord compression by revealing the loss of subarachnoid space, attenuation of the

transverse ligament, and bony and soft tissue changes in patients with C1 to C2 subluxation (image 2) [27,28]. However,

not all studies have found that CT is helpful in this setting. In one study of 12 patients, for example, CT provided additional

useful information in only one patient [28]. CT and CT angiography are useful for preoperative planning. The reformatted

sagittal CT scan can precisely document the position of the odontoid with respect to the foramen magnum, the degree of

atlantoaxial dislocation, and the relationships among the upper cervical spine joints [ 29].

CT is also helpful in planning the best surgical technique to be used in each case and in assessing the size of the

implants to be used. It is used to determine the type of fixation that can be used, such as C-1 posterior arch versus lateral

mass screws or C-2 pars, pedicle, or laminar screws [30]. A contrast-enhanced CT scan can be useful to diagnose

inflammatory soft tissue proliferation in patients unable to undergo MRI (eg, those with aneurysm clips, body implants,

Peripheral paresthesias without evidence of peripheral nerve disease or compression

Lhermittes phenomenon, an electric shock-like sensation in the neck radiating down the spine or into the arms,

produced by forward flexion of the neck

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

Increased deep tendon reflexes (seen in myelopathy)

Extensor plantar responses

Hoffmans sign

Muscle weakness, spasticity, or muscle atrophy

Gait disordersDecreased deep tendon reflexes (seen in radiculopathy)


4/14

wires or plates, some heart valves, some implanted electrodes) [31].

Magnetic resonance imaging MRI is particularly valuable in the assessment of cervical spine disease in RA, because

it permits visualization of the pannus producing cord compression, the spinal cord, and bone (image 3) [32-35]. 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 [36]. MRI can provide information about neural tissue (spinal cord

and nerve roots) and the contents of the epidural space and is the radiological modality of choice in evaluating for possible

spinal cord compression [37].

The development of neurological dysfunction is strongly associated with MRI evidence of spinal canal stenosis,

particularly in patients with evidence of upper cervical cord or brainstem compression or of subaxial myelopathy [38]. Bone

marrow edema (BME) can be observed by MRI in patients with early cervical spine involvement the edema may be seen

in the odontoid process, in the vertebral endplates, and in the subaxial interapophyseal joints [ 39]. Higher erythrocyte

sedimentation rates were associated with more severe atlantoaxial joint synovitis.

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 [ 25].

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 [40].

The information gained from MRI is sufficiently additive to warrant the increased cost of this procedure, particularly if

surgery is contemplated [33,41]. However, one drawback of MRI is that it often underestimates the degree of atlantoaxial

subluxation when compared with flexion-extension plain film radiography. This 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 [42]. 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 worst case, the measured

distance differed by 7 mm. Thus, unless flexion and extension MR images document excessive subluxation, plain film

flexion-extension radiography is still needed to assess atlantoaxial stability, especially in patients with RA scheduled to

undergo surgery requiring manipulation of the neck for either anesthesia or surgery. (See 'Conventional radiography'

above.)

NATURAL HISTORY As noted above, the onset of atlantoaxial subluxation alone is not inexorably associated with

neurologic dysfunction or with an increased risk of death [43]. Although radiographic progression is common, it does not

always correlate with neurologic deterioration [18,44-47]. Patients with plain film radiographic evidence of cervical

subluxation, with or without neurologic symptoms, have a five-year mortality rate of 17 percent [ 7].

However, some patients with severe dislocation may be at risk of death. In one series of 104 consecutive autopsies of

patients with rheumatoid arthritis (RA), 11 cases of severe dislocation were found [48]. In all 11, the odontoid protruded

posterosuperiorly and impinged on the medulla within the foramen magnum. In five, 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 progresses rapidly, and death may quickly ensue [49,50]. 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 [51]. 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 neurological deficit) treated nonoperatively. The 10-year overall survival

rate was 40 percent [50].

Magnetic resonance imaging (MRI) findings may be more helpful than plain film radiography in determining prognosis. As

an example, among 82 patients with MRI evidence of cord compression at the level of C1 to C2, 60 percent deteriorated

with conservative management over a median of 12 months [52]. Those with subaxial cord compression fared better, with

only 18 percent worsening with time. Among all patients, nine eventually required surgical intervention (six due to a

combination of pain and progressive neurologic deficits, two due to pain only, and one due to painless neurologic

deterioration).

An inability to walk preoperatively also confers a poor prognosis. In one study, only 20 percent of such patients improved

after treatment [53].


5/14

PREVENTION Limited evidence suggests that the administration of combination therapy consisting of disease

modifying antirheumatic drugs (DMARDs) may help prevent the development of cervical spine subluxation. As an

example, 195 patients with rheumatoid arthritis (RA) of recent onset (two years or less) were randomly assigned to a

regimen of sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone or to sulfasalazine alone [54]. 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 significantly associated with initial

single DMARD therapy [55]. 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).

In a study of 91 patients with RA treated with biologicals, 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) [56].

An overview of the management of RA is presented elsewhere. (See "General principles of management of rheumatoid

arthritis in adults".)

TREATMENT Patients with cervical subluxation are treated medically and/or surgically based largely upon the

presence or absence of signs of spinal cord compression.

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. Although thesubject 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. Spinal manipulation is contraindicated.

The role of neck muscle strengthening exercises is uncertain. A decrease in anterior atlantoaxial subluxation was noted in

a subgroup of seven patients with rheumatoid arthritis (RA) and unstable atlantoaxial joints during active isometric neck

flexor muscle contraction [59]. While this suggests 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 were 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 "Overview of the treatment of chronic pain"). These patients may

obtain some benefit from local nerve blocks, although the relief is generally temporary.

Surgery Patients with subluxation and signs of spinal cord compression have a grave prognosis without surgical

intervention to provide stability to the spine [ 1,19,50]. Although surgery for atlantoaxial subluxation has attendant risks,

some data indicate that early operative treatment may delay the detrimental course of cervical myelopathy in RA [ 50,60].

(See 'Natural history' above.)

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 an observational study that compared 19 patients with symptomatic

atlantoaxial subluxation who underwent laminectomy and occipitocervical fusion with 21 others who were managed

conservatively [51]. 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


6/14

neurologic symptoms [61]. Such symptoms were associated with increased risk of death during the course of the study.

There were reduced survival for patients with subaxial subluxations and an association of increased vertical settling with

sudden death. There were few perioperative or postoperative complications.

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 if symptoms develop, which is

not uncommon. 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 [ 44].

Some data support the hypothesis that early C1 to C2 fusion for atlantoaxial subluxation, before the development of

superior migration of the odontoid, 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 [62]:

A limiting factor is that the incidence of sustained neurologic deterioration related to surgery may be as high as 6 percent

[63]. As a result, a skilled surgical team and a careful assessment of each patient are important elements of any

therapeutic regimen.

Fortunately, the prognosis for patients with surgery appears to be improving due, in part, to earlier referral, enhanced

technique, and better perioperative management. 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) [64]. 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 systematic literature review identified 23 observational studies describing the neurologic outcome after surgery for 752

patients [50]. Patients with Ranawat I (asymptomatic patients with no neurologic deficit) and II (patients with subjective

weakness with hyperreflexia and dysesthesia) neurologic status rarely deteriorated. Ranawat III patients (those with

objective weakness and long tract signs) typically did not recover completely. The 10-year survival rates mirrored the

Ranawat class and ranged from 77 percent to 30 percent for Ranawat I (no deficit) and IIIB (nonambulatory patients with

objective weakness and long tract signs), respectively [50]. 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). The evidence is weak, however, and the ideal treatment for asymptomatic patients with radiographic

instability awaits the results of a randomized control trial [65].

Even though Ranawat IIIB patients have a significantly worse outcome than all other groups [ 50], surgery may still offer

the best quality of life and survival for these severely disabled patients [66]. 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

brain stems and spinal cords 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 [67].

Transpedicle screw fixation using stereotactic guidance has also been used for stabilization [ 68]. Because the diameter of

cervical pedicles is very small, this is considered a procedure with significant risk. However, use of full-scale, three-

dimensional models in preoperative planning may lessen morbidity [69].

Occipitocervical fixation has also been employed to treat patients with unstable cervical spines. When this procedure was

employed in 163 RA patients, 88 percent improved, 7 percent remained unchanged, and 5 percent progressed [ 70].

Complications included infection (10 percent) and progressive subluxation that required reoperation (4 percent).

Fifteen percent developed cervical instability this occurred in 5.5 percent of those with atlantoaxial subluxation and

in 36 percent of those with 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.


7/14

SUMMARY AND RECOMMENDATIONS

Cervical joint destruction in patients with rheumatoid arthritis (RA) may lead to vertebral malalignment (eg,

subluxation), causing pain, neurological deficit, and deformity. Risk factors for cervical subluxation include older age

at onset of RA, more active synovitis, higher levels of C-reactive protein, 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 appear to

require surgery since the 1990s. (See 'Cervical involvement' above and 'Prevalence' 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 'Atlantoaxial disease' above.)

The two possible mechanisms for involvement of the intervertebral joints in the cervical spine in RA are 1) extension

of the inflammatory process from adjacent neurocentral joints (the joints of Luschka, which are lined by synovium)

into the discovertebral area and 2) chronic cervical instability initiated by apophyseal joint destruction, subsequently

leading to vertebral malalignment or subluxation. (See 'Pathogenesis' 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 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 symptoms of spinal cord compression that demand

immediate attention and intervention include (see 'Symptoms' 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 nystagmusPeripheral paresthesias without evidence of peripheral nerve disease or compression

Lhermittes phenomenon, an electric shock-like sensation in the neck radiating down the spine or into the arms,

produced by forward flexion of the neck

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

Hoffmans sign muscle weakness, spasticity, or muscle atrophy gait disorders and decreased deep tendon reflexes

(seen in radiculopathy). (See 'Physical findings' above.)

Patients with mild, nonspecific neck or occipital pain can be evaluated initially by conventional radiography, butpatients 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.)

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 dislocation 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 'Natural

history' above.)


8/14

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Bland J. Rheumatoid arthritis of the cervical spine. J Rheumatol 1974 1:319.

2. Ball J. Enthesopathy of rheumatoid and ankylosing spondylitis. Ann Rheum Dis 1971 30:213.

3. Neva MH, Isomki P, Hannonen P, et al. Early and extensive erosiveness in peripheral joints predicts atlantoaxialsubluxations in patients with rheumatoid arthritis. Arthritis Rheum 2003 48:1808.

4. Paimela L, Laasonen L, Kankaanp E, Leirisalo-Repo M. Progression of cervical spine changes in patients withearly rheumatoid arthritis. J Rheumatol 1997 24:1280.

5. Santavirta S, Kankaanp U, Sandelin J, et al. Evaluation of patients with rheumatoid cervical spine. Scand JRheumatol 1987 16:9.

6. Kauppi M, Sakaguchi M, Konttinen YT, et al. Pathogenetic mechanism and prevalence of the stable atlantoaxialsubluxation in rheumatoid arthritis. J Rheumatol 1996 23:831.

7. Chang DJ, Paget SA. Neurologic complications of rheumatoid arthritis. Rheum Dis Clin North Am 1993 19:955.

8. Davidson RC, Horn JR, Herndon JH, Grin OD. Brain-stem compression in rheumatoid arthritis. JAMA 1977238:2633.

9. Martel W. Pathogenesis of cervical discovertebral destruction in rheumatoid arthritis. Arthritis Rheum 1977 20:1217.

10. Bywaters EG. Rheumatoid and other diseases of the cervical interspinous bursae, and changes in the spinousprocesses. Ann Rheum Dis 1982 41:360.

11. Winfield J, Young A, Williams P, Corbett M. Prospective study of the radiological changes in hands, feet, andcervical spine in adult rheumatoid disease. Ann Rheum Dis 1983 42:613.

12. Collins DN, Barnes CL, FitzRandolph RL. Cervical spine instability in rheumatoid patients having total hip or knee

arthroplasty. Clin Orthop Relat Res 1991 :127.13. Ward MM. Decreases in rates of hospitalizations for manifestations of severe rheumatoid arthritis, 1983-2001.

Arthritis Rheum 2004 50:1122.

14. Neva MH, Kaarela K, Kauppi M. Prevalence of radiological changes in the cervical spine--a cross sectional studyafter 20 years from presentation of rheumatoid arthritis. J Rheumatol 2000 27:90.

15. Henderson DR. Vertical atlanto-axial subluxation in rheumatoid arthritis. Rheumatol Rehabil 1975 14:31.

16. Zikou AK, Alamanos Y, Argyropoulou MI, et al. Radiological cervical spine involvement in patients with rheumatoidarthritis: a cross sectional study. J Rheumatol 2005 32:801.

17. Fujiwara K, Fujimoto M, Owaki H, et al. Cervical lesions related to the systemic progression in rheumatoid arthritis.Spine (Phila Pa 1976) 1998 23:2052.

18. Stevens JC, Cartlidge NE, Saunders M, et al. Atlanto-axial subluxation and cervical myelopathy in rheumatoidarthritis. Q J Med 1971 40:391.

19. Nakano KK, Schoene WC, Baker RA, Dawson DM. The cervical myelopathy associated with rheumatoid arthritis:analysis of patients, with 2 postmortem cases. Ann Neurol 1978 3:144.

20. Boden SD, Dodge LD, Bohlman HH, Rechtine GR. Rheumatoid arthritis of the cervical spine. A long-term analysiswith predictors of paralysis and recovery. J Bone Joint Surg Am 1993 75:1282.

21. Mayer JW, Messner RP, Kaplan RJ. Brain stem compression in rheumatoid arthritis. JAMA 1976 236:2094.

22. MARTEL W. The occipito-atlanto-axial joints in rheumatoid arthritis and ankylosing spondylitis. Am J RoentgenolRadium Ther Nucl Med 1961 86:223.

23. Weissman BN, Aliabadi P, Weinfeld MS, et al. Prognostic features of atlantoaxial subluxation in rheumatoid arthritispatients. Radiology 1982 144:745.

24. Lipson SJ. Rheumatoid arthritis in the cervical spine. Clin Orthop Relat Res 1989 :121.

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. Such patients may

benefit from rigid cervical collars. Surgery should be considered carefully and on an individualized basis among

patients with subluxation but without signs or symptoms of cord compression. 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.)


9/14

25. Bell GR, Stearns KL. Flexion-extension MRI of the upper rheumatoid cervical spine. Orthopedics 1991 14:969.

26. Neva MH, Hkkinen A, Mkinen H, et al. High prevalence of asymptomatic cervical spine subluxation in patientswith rheumatoid arthritis waiting for orthopaedic surgery. Ann Rheum Dis 2006 65:884.

27. Raskin RJ, Schnapf DJ, Wolf CR, et al. Computerized tomography in evaluation of atlantoaxial subluxation inrheumatoid arthritis. J Rheumatol 1983 10:33.

28. Braunstein EM, Weissman BN, Seltzer SE, et al. Computed tomography and conventional radiographs of thecraniocervical region in rheumatoid arthritis. A comparison. Arthritis Rheum 1984 27:26.

29. Holmes JF, Akkinepalli R. Computed tomography versus plain radiography to screen for cervical spine injury: ameta-analysis. J Trauma 2005 58:902.

30. Joaquim AF, Ghizoni E, Anderle DV, et al. Axis instrumentation: surgical results. Arq Neuropsiquiatr 2012 70:857.

31. Czerny C, Grampp S, Henk CB, et al. Rheumatoid arthritis of the craniocervical region: assessment andcharacterization of inflammatory soft tissue proliferations with unenhanced and contrast-enhanced CT. Eur Radiol2000 10:1416.

32. Breedveld FC, Algra PR, Vielvoye CJ, Cats A. Magnetic resonance imaging in the evaluation of patients withrheumatoid arthritis and subluxations of the cervical spine. Arthritis Rheum 1987 30:624.

33. DAVIS FW Jr, MARKLEY HE. Rheumatoid arthritis with death from medullary compression. Ann Intern Med 195135:451.

34. Stiskal MA, Neuhold A, Szolar DH, et al. Rheumatoid arthritis of the craniocervical region by MR imaging: detectionand characterization. AJR Am J Roentgenol 1995 165:585.

35. Glew D, Watt I, Dieppe PA, Goddard PR. MRI of the cervical spine: rheumatoid arthritis compared with cervical

spondylosis. Clin Radiol 1991 44:71.

36. Tehranzadeh J, Ashikyan O, Dascalos J. Magnetic resonance imaging in early detection of rheumatoid arthritis.Semin Musculoskelet Radiol 2003 7:79.

37. Joaquim AF, Ghizoni E, Tedeschi H, et al. Radiological evaluation of cervical spine involvement in rheumatoidarthritis. Neurosurg Focus 2015 38:E4.

38. Narvez JA, Narvez J, Serrallonga M, et al. Cervical spine involvement in rheumatoid arthritis: correlation betweenneurological manifestations and magnetic resonance imaging findings. Rheumatology (Oxford) 2008 47:1814.

39. Narvez JA, Narvez J, de Albert M, et al. Bone marrow edema in the cervical spine of symptomatic rheumatoidarthritis patients. Semin Arthritis Rheum 2009 38:281.

40. Dickman CA, Mamourian A, Sonntag VK, Drayer BP. Magnetic resonance imaging of the transverse atlantalligament for the evaluation of atlantoaxial instability. J Neurosurg 1991 75:221.

41. Martel W. Fatal atlanto-axial luxation in rheumatoid arthritis. Arthritis Rheum 1963 6:224.42. Laiho K, Soini I, Kautiainen H, Kauppi M. Can we rely on magnetic resonance imaging when evaluating unstable

atlantoaxial subluxation? Ann Rheum Dis 2003 62:254.

43. Pellicci PM, Ranawat CS, Tsairis P, Bryan WJ. A prospective study of the progression of rheumatoid arthritis of thecervical spine. J Bone Joint Surg Am 1981 63:342.

44. Smith PH, Benn RT, Sharp J. Natural history of rheumatoid cervical luxations. Ann Rheum Dis 1972 31:431.

45. Isdale IC, Conlon PW. Atlanto-axial subluxation. A six-year follow-up report. Ann Rheum Dis 1971 30:387.

46. Mathews JA. Atlanto-axial subluxation in rheumatoid arthritis. A 5-year follow-up study. Ann Rheum Dis 197433:526.

47. Winfield J, Cooke D, Brook AS, Corbett M. A prospective study of the radiological changes in the cervical spine inearly rheumatoid disease. Ann Rheum Dis 1981 40:109.

48. Mikulowski P, Wollheim FA, Rotmil P, Olsen I. Sudden death in rheumatoid arthritis with atlanto-axial dislocation.Acta Med Scand 1975 198:445.

49. Meijers KA, Cats A, Kremer HP, et al. Cervical myelopathy in rheumatoid arthritis. Clin Exp Rheumatol 1984 2:239.

50. Wolfs JF, Kloppenburg M, Fehlings MG, et al. Neurologic outcome of surgical and conservative treatment ofrheumatoid cervical spine subluxation: a systematic review. Arthritis Rheum 2009 61:1743.

51. Matsunaga S, Sakou T, Onishi T, et al. Prognosis of patients with upper cervical lesions caused by rheumatoidarthritis: comparison of occipitocervical fusion between c1 laminectomy and nonsurgical management. Spine (PhilaPa 1976) 2003 28:1581.

52. Hamilton JD, Johnston RA, Madhok R, Capell HA. Factors predictive of subsequent deterioration in rheumatoidcervical myelopathy. Rheumatology (Oxford) 2001 40:811.

53. Casey AT, Crockard HA, Bland JM, et al. Surgery on the rheumatoid cervical spine for the non-ambulant


10/14

myelopathic patient-too much, too late? Lancet 1996 347:1004.

54. Neva MH, Kauppi MJ, Kautiainen H, et al. Combination drug therapy retards the development of rheumatoidatlantoaxial subluxations. Arthritis Rheum 2000 43:2397.

55. Kauppi MJ, Neva MH, Laiho K, et al. Rheumatoid atlantoaxial subluxation can be prevented by intensive use oftraditional disease modifying antirheumatic drugs. J Rheumatol 2009 36:273.

56. Kaito T, Ohshima S, Fujiwara H, et al. Predictors for the progression of cervical lesion in rheumatoid arthritis underthe treatment of biological agents. Spine (Phila Pa 1976) 2013 38:2258.

57. Kauppi M, Anttila P. A stiff collar for the treatment of rheumatoid atlantoaxial subluxation. Br J Rheumatol 199635:771.

58.Althoff B, Goldie I F. Cervical collars in rheumatoid atlanto-axial subluxation: a radiographic comparison. Ann RheumDis 1980 39:485.

59. Hakkinen A, Makinen H, Ylinen J, et al. Stability of the upper neck during isometric neck exercises in rheumatoidarthritis patients with atlantoaxial disorders. Scand J Rheumatol 2008 37:343.

60. Schmitt-Sody M, Kirchhoff C, Buhmann S, et al. Timing of cervical spine stabilisation and outcome in patients withrheumatoid arthritis. Int Orthop 2008 32:511.

61. Paus AC, Steen H, Rislien J, et al. High mortality rate in rheumatoid arthritis with subluxation of the cervical spine:a cohort study of operated and nonoperated patients. Spine (Phila Pa 1976) 2008 33:2278.

62.Agarwal AK, Peppelman WC, Kraus DR, et al. Recurrence of cervical spine instability in rheumatoid arthritisfollowing previous fusion: can disease progression be prevented by early surgery? J Rheumatol 1992 19:1364.

63. Yonenobu K, Hosono N, Iwasaki M, et al. Neurologic complications of surgery for cervical compression myelopathy.

Spine (Phila Pa 1976) 1991 16:1277.64. Hamilton JD, Gordon MM, McInnes IB, et al. Improved medical and surgical management of cervical spine disease

in patients with rheumatoid arthritis over 10 years. Ann Rheum Dis 2000 59:434.

65. Wolfs JF, Peul WC, Boers M, et al. Rationale and design of The Delphi Trial--I(RCT)2: international randomizedclinical trial of rheumatoid craniocervical treatment, an intervention-prognostic trial comparing 'early' surgery withconservative treatment [ISRCTN65076841]. BMC Musculoskelet Disord 2006 7:14.

66. Nannapaneni R, Behari S, Todd NV. Surgical outcome in rheumatoid Ranawat Class IIIb myelopathy. Neurosurgery2005 56:706.

67. Henderson FC, Geddes JF, Crockard HA. Neuropathology of the brainstem and spinal cord in end stage rheumatoidarthritis: implications for treatment. Ann Rheum Dis 1993 52:629.

68. Rath SA, Moszko S, Schffner PM, et al. Accuracy of pedicle screw insertion in the cervical spine for internalfixation using frameless stereotactic guidance. J Neurosurg Spine 2008 8:237.

69. Mizutani J, Matsubara T, Fukuoka M, et al. Application of full-scale three-dimensional models in patients withrheumatoid cervical spine. Eur Spine J 2008 17:644.

70. Zygmunt SC, Christensson D, Sveland H, et al. Occipito-cervical fixation in rheumatoid arthritis--an analysis ofsurgical risk factors in 163 patients. Acta Neurochir (Wien) 1995 135:25.

Topic 7518 Version 11.0


11/14

GRAPHICS

Anterior subluxation of C1 on C2 in rheumatoid arthritis on radiography

A lateral examination of the cervical spine (A) shows anterior subluxation of C1 on C2. The magnified vi

shows a 12 mm separation between the posterior border of the arch of C1 (arrowhead) and the anterior b

of the odontoid process of C2 (arrow).

RA: rheumatoid arthritis.

Graphic 100051 Version 2.0


12/14

Anterior dislocation of C1 on C2 in rheumatoid arthritis on CT

A sagittal reconstruction of a CT scan (A) shows a 7.5 mm separation between the posterior part of

the arch of C1 (arrowhead) and the anterior aspect of the dens (arrow). Image B is a coronal

reconstruction of a CT scan and shows a large erosion on the lateral aspect of the dens (arrowhead).

Image C is an axial image and shows a large erosion (arrowhead) on the eccentrically positioned

dens. Image D is an axial image using soft tissue windows through the same region as C, and shows

extensive pannus formation around the dens (asterisks), which impinges on the CSF space (arrow)

surrounding the spinal cord (arrowhead).

CT: computed tomography.



13/14

Anterior subluxation of C1 on C2 in rheumatoid arthritis with cord indentatio

on MRI

A T2-weighted image of the cervical spine in the sagittal plain (A) shows a 5 mm separation (arrows)

between the posterior border of C1 arch (anterior arrow) and the anterior border of the dens (posterior

arrow). Multilevel spondylosis is also present between C3 and C7. Image B is a magnified view of image

and shows the C1-C2 separation (arrows), pannus formation posterior to the dens (asterisk), withimpingement on the cord and the anterior CSF space (dashed arrow), and the cord (arrowhead).

MRI: magnetic resonance imaging.



14/14

Contributor Disclosures

Peter H Schur, MD Nothing to disclose. Bradford L Currier, MD Consultant/Advisory Boards: Zimmer Spine [Spinesurgery (Cervical spinal implants)]. Patent Holder: DePuy Spine [Spine surgery (Cervical spinal implants)]. Ravinder NMaini, BA, MB BChir, FRCP, FMedSci, FRS Patent Holder: Inventor [Inventor's share of royalties received by theKennedy Trust for Rheumatology Research for anti-TNF treatment of RA: Janssen-Centocor, AbbVie, Hospira, andCelltrion]. Paul L Romain, MD Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed byvetting through a multi-level review process, and through requirements for references to be provided to support the content.

Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

Cervical Subluxation in Rheumatoid Arthritis

Documents

Transcript of Cervical Subluxation in Rheumatoid Arthritis