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Degenerative Cervical Spondylosis

The new england journal of medicine

Review Article

Allan H. Ropper, M.D., Editor Degenerative Cervical Spondylosis

Nicholas Theodore, M.D.​​

egenerative cervical spondylosis is a chronic, progressive de- From the Department of , terioration of osseocartilaginous components of the cervical spine that is Johns Hopkins School of Medicine, Balti- more. Address reprint requests to Dr. most often related to aging. Radiographic evidence of degeneration of the Theodore at Johns Hopkins Hospital, D 600 N. Wolfe St., Meyer 7-113, Baltimore, cervical spine occurs in virtually all persons as they age; however, not all persons have the typical symptoms of or neurologic deficits that correspond to MD 21287, or at ­theodore@​­jhmi​.­edu. the mechanical compression of neural elements. Symptomatic cervical spondylosis N Engl J Med 2020;383:159-68. is initially managed with nonsurgical treatment options, which usually result in DOI: 10.1056/NEJMra2003558 Copyright © 2020 Massachusetts Medical Society. abatement of symptoms. Surgical intervention may be indicated if there is clini- cally significant neurologic dysfunction or progressive instability or deformity of the cervical spine. No currently approved therapy addresses the cause of degen- erative cervical spondylosis or reverses the deterioration. In select patients, surgi- cal intervention can lead to favorable outcomes.

Terminology and Epidemiology Degeneration of the cervical spine has acquired many equivalent names, including degenerative cervical spondylosis, cervical degenerative disease, cervical spondylo- sis, cervical , and neck arthritis. The term spondylosis comes from the Greek word spóndylos, meaning . In general, these terms refer to age- related wear and tear that affect elements of the cervical spine over time, including the intervertebral disks, facet joints, and other connective-tissue structures (e.g., cervical spinal ligaments). However, cervical spine degeneration may also have immune inflammatory components.1,2 The disorder may be associated with gener- alized , mechanical or axial neck pain, compression and inflammation of the cervical roots exiting the cervical spine (cervical ), and compression and inflammation of the adjacent cervical (cervical my- elopathy).3 Although age-related degenerative changes of the spine are almost universal, they may begin as early as in the first decade of life.4 Population-based studies have shown that approximately 80 to 90% of people have disk degeneration on magnetic resonance imaging (MRI) by the age of 50 years.5,6 A review of the global burden of low back and neck pain estimated that in 2015, more than a third of a billion people worldwide had mechanical neck pain of at least 3 months’ duration,7 underscoring the global health implications of degenerative cervical spondylosis.8 A much smaller number of people have cervical radiculopathy (esti- mated annual incidence, approximately 83 cases per 100,000 persons)9 and my- elopathy (approximately 4 per 100,000)10 as a result of cervical spondylosis. Clinical features of spondylosis are more common in men than in women, with a peak incidence between the ages of 40 and 60 years for both men and women.11,12

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Pathogenesis and annulus and decreased yield strength predis- Pathophysiology poses the annulus to fissuring, with resultant herniation of the nucleus pulposus (the common Although degenerative cervical spondylosis can condition of disk herniation), which impinges affect any component of the cervical spine, such on the spinal cord or nerve roots. as bone quality and joint structures,13 the most In addition, disk desiccation is associated with clinically significant changes occur in the inter- loss of disk height, which is one reason that vertebral disks and facet joints. The interverte- people “shrink” with age. Loss of disk height also bral disk consists of the annulus fibrosus on the narrows the foramina, through which nerve roots exterior border of the disk and the nucleus exit the spinal column, and leads to circumfer- pulposus in the interior.14 Like most dense con- ential bulging of the annulus. nective tissue (e.g., ligaments), the intervertebral Finally, nociceptive nerve fibers that are pres- disk is essentially avascular.15,16 Nutrient and ent in the annulus and nucleus pulposus become waste exchange occur primarily through diffu- sensitized by the cytokine milieu of the degen- sion across the capillary beds in the adjacent erative disk, putatively leading to a syndrome of superior and inferior vertebral end plates.17 The pure diskogenic pain.24,25 Mechanical neck pain intervertebral disks are metabolically active tis- is more often due to the distortion of surround- sues, and cells deep within the disk, where oxy- ing soft tissues, including muscles and liga- gen is scarce, have adopted mechanisms to ments, and the cause of pain in patients with compensate for the relative hypoxia, including degenerative cervical spondylosis is often diffi- the up-regulation of hypoxia-inducible factors cult to determine. It has been suggested that the (e.g., HIF-1α).18,19 Inner intervertebral disk cells central nervous system may become sensitized (nucleopulpocytes) exist in a precarious state and perpetuate neck discomfort in patients with and may die in the presence of age-related chronic spinal pain.26,27 changes such as vertebral bony end-plate calcifi- Degeneration of the cervical facet joints, a set cation that decrease the limited exchange of of two synovial joints that stabilize adjacent ver- nutrient and waste products.17 tebrae at every spinal level below C1, may occur The loss of intervertebral disk cells is thought as a result of — or independent of — degenera- to contribute to a shift from tissue homeostasis tion of the intervertebral disk. Such degenera- toward net catabolism, leading to intervertebral tion leads to pain and radiculopathy. disk deterioration.20 However, the events trigger- occurs if vertebral bodies are dis- ing catabolic processes within the intervertebral placed, a condition termed .4 disk have not been clearly defined. Such events This process is the result of damage to several may have a genetic basis or may be related to elements of the spinal architecture. Normally, previous spinal trauma, including subclinical the cervical facet joints provide load-bearing and unnoticed injuries.21,22 Up-regulation of pro- support alongside the intervertebral disk and inflammatory cytokines within the disk, includ- stabilize the neck during flexion, extension, and ing tumor necrosis factor α, interleukin-1β, and rotation. In the context of disk degeneration, the interleukin-6, occurs concomitantly with the facet joints may be subjected to increased load loss of matrix-producing cells, further promot- bearing, which leads to osseocartilaginous al- ing the loss or senescence of native matrix-pro- terations and destabilizes the joints.13 Degenera- ducing cells and subsequent replacement with tion of the facet joints is similar to degeneration fibroblast-like cells.20 As a result, the production seen in other diarthrodial joints, such as the of hydrophilic proteoglycans is decreased, lead- knee, and may be characterized by joint-space ing to gradual desiccation of the disk and the narrowing, subchondral sclerosis, and osteo- transfer of biomechanical loads from the nucle- phyte formation. These changes narrow the us pulposus to the surrounding annulus.13 Fur- spinal canal and neural foramina and decrease thermore, this degenerative process is accompa- neck mobility. Like the intervertebral disk, the nied by the secondary up-regulation of matrix facet joints are innervated by nociceptive nerve metalloproteinases by resident disk cells, which fibers and may be sources of cervical spine lowers the yield strength of the annulus.23 The pain.28 Cervical syndrome, which is combination of increased load sharing by the focal pain caused by degeneration of a cervical

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Table 1. Worrisome Signs and Symptoms in the Evaluation of Patients with Degenerative Cervical Spondylosis.*

Signs and Symptoms Cause Physical Examination History of cancer (especially breast, prostate, Cancer Variable findings, neurologic deficit, or lung), weight loss, night sweats, fever, exquisite tenderness over vertebral nocturnal neck pain body History of intravenous drug use, immunocom- Spinal abscess Usually severe local pain promised status, fever, diabetes, recent sepsis Decreased dexterity in hands or feet, gait and Spondylitic myelopathy Hyperreflexia, clonus, ataxia, Romberg’s balance instability, increased urinary sign, atrophy of intrinsic hand frequency and urgency muscles

* The information is from Childress and Becker.31

facet joint, is recognized by some clinicians as a or upper back to the proximal arm, is the most subcategory of degenerative cervical spondylosis common symptom of cervical degenerative ra- that calls for distinct treatment.29,30 diculopathy.9 Radicular neck pain may also be accompanied by painful neck spasms. Patients Clinical Presentation and with cervical degenerative radiculopathy may Diagnosis have , numbness, or weakness that often — but not always — corresponds to der- Patients with degenerative cervical spondylosis matomal distributions of the affected cervical may present with mechanical neck pain, radicu- nerve root.31 Diminished deep-tendon reflexes, lopathy, myelopathy, or a combination of these such as those of the biceps (C6 nerve root) or symptoms. Mechanical neck pain may be iso- triceps (C7 nerve root), are corroborative of lated to the neck or may radiate broadly, such nerve-root compression. as to the shoulders, head, chest, and back. The Provocative tests used to aid in the diagnosis source of the pain is often difficult for patients of cervical degenerative radiculopathy include to pinpoint. This complicates management, the Spurling test, the shoulder-abduction test, since the pain could stem from the degenerated and the cervical-traction test.33,34 In the typical intervertebral disk (pure diskogenic pain), the application of the Spurling test, the patient’s degenerated facet joints, or the muscular and neck is turned to the side of the ligamentous structures. The pain is often wors- and is then slightly extended. Downward pres- ened by neck motion and relieved by rest and sure is applied to the top of the patient’s head, immobilization. However, neck pain is relatively which narrows the neural foramina on the af- common in the general population, affecting an fected side. If the pain is elicited or worsened, it estimated 15% of people at any time, and is not can be attributed to radiculopathy. The test may specific to degenerative cervical spondylosis.3 A be repeated by turning the patient’s head to the patient presenting with neck pain may be asked side opposite the pain; if the pain is worsened by about red-flag signs and symptoms, such as a this maneuver, a musculoskeletal cause is sug- history of cancer, gait instability or sensory loss gested. The shoulder-abduction test is another associated with myelopathy, and fever with noc- useful diagnostic tool. This test is performed by turnal pain suggestive of spinal abscess — all of placing the palm or forearm of the affected arm which require rapid evaluation (Table 1). on top of the patient’s head. If the radicular pain Cervical radiculopathy from spondylosis is is relieved, radiculopathy is the likely source of caused by mechanical compression and inflam- the pain. Manual cervical traction may be used mation of a cervical nerve root, most commonly as a test to expand the neural foramina; if ra- C6 or C7.31,32 The compression may be acute (e.g., dicular pain is relieved in this way, then radicu- caused by an abruptly herniated disk) or chronic lopathy is suggested. (e.g., the result of hypertrophied facet joints). Cervical degenerative myelopathy is the least Pain arising from the compressed and inflamed common but most worrisome presentation of nerve root, mainly radiating from the shoulder degenerative cervical spondylosis. It is caused by

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Table 2. Differential Diagnosis for Cervical Degenerative Spondylosis.*

Clinical Feature Acute Conditions Chronic Conditions Neck pain Cervical strain or sprain, painful interverte- Fibromyalgia, failed surgical fusion, referred visceral bral disk, painful facet joint pain, hypochondriasis and somatoform disorders Radiculopathy Intervertebral disk herniation, brachial Intervertebral disk herniation, shoulder disorder, plexitis entrapment neuropathy, focal facet hypertrophy Myelopathy Intervertebral disk herniation, pathologic Intervertebral disk herniation, spinal instability, central fracture, Guillain–Barré syndrome canal stenosis, multiple sclerosis, neoplasm, infec- tion, myopathies, syringomyelia, arteriovenous malformation, vitamin B12 deficiency

* The information is from Voorhies.3

mechanical compression and is associated with that virtually all patients older than 50 years of inflammation and edema of the spinal cord; age have cervical degenerative changes on one or inflammation and edema lead to slow, progres- more forms of imaging, and many findings are sive deterioration of neurologic function as a not specific. For these reasons, diagnostic imag- result of narrowing of the spinal canal and com- ing is often not recommended for patients who pression of the long tracts and local segmental initially present with nontraumatic neck pain elements of the spinal cord.35 Both static (at rest) without neurologic symptoms or signs or red and dynamic (repetitive motion) compressive fac- flags. tors contribute to deterioration.36,37 For example, For patients with persistent neck, shoulder, or an already compressed spinal cord may sustain arm pain and suspected radiculopathy, an initial further compression on neck flexion, which in- radiographic evaluation may be performed, with creases tension on the spinal cord because of its the use of anteroposterior, lateral, and oblique relatively fixed longitudinal position, maintained radiographs, which are relatively inexpensive by the dentate ligaments and cervical nerve and provide information pertaining to degenera- roots. Patients with myelopathy may present tive changes and alignment.40 Lateral flexion or with a variety of subtle neurologic findings, extension views may also be obtained during the which they may attribute to natural loss of func- initial evaluation and may disclose cervical in- tion with age. These include loss of manual stability, limited range of motion, and fused dexterity; gait and balance disturbances, espe- cervical spine segments.41 For patients with pro- cially in the absence of visual cues (Romberg’s gressive neurologic impairments or any feature sign); sensory loss in the hands or feet; arm or that suggests myelopathy, cervical spine MRI hand weakness; and defecatory or urinary fre- without the administration of contrast material quency, urgency, or hesitancy. There may be up- is the preferred imaging technique, since it pro- per-motor-neuron signs, including clonus, hyper- vides information about osseous, soft-tissue, reflexia, Hoffmann’s sign, and Babinski’s sign.38 and spinal cord structures (Fig. 1).42 The pres- Patients with symptoms of myelopathy almost ence of an abnormal signal within the cervical always have associated neck pain and stiffness cord or adjacent to the level of compression by and may have pain in the arms or shoulders. spondylosis is considered a serious finding, Radicular features, mentioned above, are also which may signify a less satisfactory outcome common in the context of cervical degenerative with surgical decompression than would other- myelopathy. Some persons have Lhermitte’s sign wise be expected. On the other hand, in some (electrical sensations radiating down the spine cases the spinal cord seems able to withstand a or across the shoulders) on neck flexion, and substantial degree of deformation, with few re- other signs and symptoms that are occasionally sulting symptoms, if the deformation develops attributable to cervical myelopathy but have slowly. The decision to surgically decompress many alternative causes.38 the spinal canal in cases of cervical spondylosis Table 2 outlines the differential diagnosis for incorporates, but does not entirely depend on, the main presentations of cervical spondylosis, such factors as the degree of disability (e.g., with or without myelopathy.3,31,39 In evaluating impairment of activities of daily living) and the patients with neck pain, it is useful to recognize rapidity of symptom progression. If MRI is con-

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A B

Figure 1. MRI Scans of the Cervical Spine in a Patient with Cervical Spondylosis. A 75-year-old man presented with a 2-year history of progressive upper-extremity and radicular pain. He reported having dropped items recently from both hands and noted dexterity and balance deficits but no bowel or bladder incontinence. A sagittal T2-weighted MRI scan shows stenosis of the central spinal canal at C4–C7, with an , deformation of the cord, disk material, and spondylolisthesis at C5–C6 (Panel A, arrow). An axial T2- weighted image shows severe foraminal stenosis (Panel B, arrow) and severe encroachment on the spinal canal by osteophyte, ligamentous, and facet hypertrophy.

traindicated or unavailable, a computed tomo- the absence of signs of nerve-root or spinal cord graphic (CT) study or CT myelography of the compression. The care of patients with chronic, cervical spine (Fig. 2) is an alternative imaging degenerative neck pain can be challenging and approach.43,44 Electrodiagnostic testing may be frustrating for both patient and health care pro- helpful in evaluating cervical radiculopathy by vider, especially given the difficulty in identify- showing denervation in muscles specifically refer- ing the cause. Many patients benefit from a re- able to a single cervical nerve root.45,46 Guide- ferral to a specialist in chronic pain management, lines for the use of injections and other ap- and many have improvement when coexisting proaches, including advanced imaging studies psychiatric disorders, including anxiety and de- such as single-photon emission CT to identify pression, are treated.52-54 In general, surgical “pain generators,” are ill defined and lack evi- outcomes for patients with chronic neck pain dence-based support.3,47,48 are limited, especially when the source of the pain cannot be identified. Treatment Approaches Most patients with degenerative cervical ra- and Outcomes diculopathy have reduced pain and improved neurologic function with nonsurgical care, in- Various treatment algorithms have been created cluding oral analgesics, epidural glucocorticoid for managing degenerative cervical spondylosis injections, physical therapy, cervical traction or and mechanical neck pain, radiculopathy, or brief immobilization in a cervical orthosis, and myelopathy.31,49-51 The management of degenera- other options, such as massage.9,31,55 Few high- tive neck pain in patients who have no neuro- quality studies have evaluated these conservative logic deficit is typically a “tincture of time,” therapies to provide a recommendation, and the along with analgesics and other conservative various approaches may offer similar rates of options, including physical therapy.3 Some pa- symptomatic improvement. tients have worsening or chronic pain, even in The severity and rate of progression of neuro-

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logic deficits are the main aspects of the evalu- Figure 3 (facing page). Cervical Spine Decompression ation of patients with degenerative cervical ra- and Fusion. diculopathy, since clinically significant motor Anterior cervical diskectomies at C3–C4 and C4–C5, weakness or worsening neurologic symptoms with the placement of bone-graft spacers where disks usually indicate the need for surgical evaluation. were removed and stabilizing screw–plate instrumen- The timing for surgical evaluation is not clear, tation, are shown schematically in Panel A and in a lat- eral radiograph in Panel C. Posterior although advancing nerve-root compression in and lateral mass screw–rod instrumentation and fu- association with weakness, atrophy, or sensory sion at C3–C6 are shown schematically in Panel B and loss, in addition to deteriorating neurologic sta- in an anteroposterior radiograph in Panel D. tus at any time, generally prompts referral to a spine surgeon. In patients with identifiable causes of nerve-root compression — for exam- In view of the progressive natural history of ple, a herniated disk — surgical outcomes are nerve-root or spinal cord compression or pain in often good.56 most patients, surgical treatment for degenera- Patients with degenerative cervical myelopa- tive cervical myelopathy can be a good op- thy are also typically referred to a spine surgeon. tion.35,36 For patients with moderate-to-severe

A B

C

Figure 2. Postmyelography CT Scans of the Cervical Spine. A 68-year-old woman had increasing hand weakness, intrinsic hand-muscle atrophy, and hand numbness. She had begun falling and had Romberg’s sign. She was unable to undergo MRI. A midsagittal CT myelogram (Panel A) shows multilevel cervical spondylosis with , disk protrusion, and cord compression at C4–C5 (arrow). An axial image at the C3–C4 disk space shows a right lateral osteophyte (Panel B, arrow) encroaching on the neural foramen, and a similar image at the C4–C5 disk space shows marked cord compression (Panel C).

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A B

C1 C1

C2 C2

C3 C3

C4 Bone Bone spacer C4 graft Metal rod and screws C5 C5

C6 C6

C7 Metal plate C7 and screws

C D

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neurologic deficits, consensus statements have hypertrophy. Why only some patients have symp- suggested that nonsurgical management, as toms after these changes occur is unclear. Cer- compared with surgery, leads to inferior clinical tain anatomical configurations, such as a con- outcomes. However, data from well-performed genitally narrow spinal canal, short pedicles, randomized trials, such as those that have been and small neural foramina, are almost certainly conducted for lumbar spine disease, are lacking, contributors to the development of symptoms and so this suggestion is driven largely by clini- for a given degree of spondylosis. Staying physi- cal experience.57 cally active, maintaining good posture, and pre- Surgical approaches to the treatment of de- venting neck injuries may all help prevent symp- generative cervical radiculopathy, myelopathy, or tomatic degenerative cervical spondylosis. In both include anterior, posterior, and anteropos- addition, smoking and obesity have been found terior techniques (Fig. 3).58-60 Each technique has to be associated with spondylosis; therefore, its proponents and inherent drawbacks, related managing these risk factors may offer benefits.62 mainly to the adequacy of decompression of the spinal cord and nerve roots, maintenance of Conclusions and stability of the spinal column, duration of the Recommendations procedure and blood loss, and time required to recover from surgery and be discharged from Degenerative cervical spondylosis is caused by the hospital. In some instances, the surgeon’s arthritic changes in the osseocartilaginous com- facility and experience with a certain procedure ponents of the cervical spine, which may com- are considerations in choosing the approach. press roots, the spinal cord, or both, The goals of surgery are to decompress the nerve causing neck pain, radiculopathy, or myelopathy. roots or spinal cord and stabilize the spine, Treatment is generally nonsurgical, especially while attempting to restore or maintain rela- for pain and mild radiculopathy, which are typi- tively normal spinal alignment. Outcomes de- cally self-limiting. However, surgery is generally pend on the severity and duration of the neuro- indicated to treat myelopathy and may be indicated logic deficit at the time of surgery. Advanced for persistent and severe nerve-root compression. age, smoking, and coexisting conditions such as obesity and diabetes mellitus have been shown Dr. Theodore reports receiving royalties and consulting fees 61 from Globus Medical and royalties from Depuy Synthes; and to negatively affect outcomes. holding patent US20130345718A10 on a surgical robot platform, licensed to Globus Medical, for which royalties are received, and holding patent US 2019/0090907 A1 on a revision connector for Prevention spinal constructs, licensed to Depuy Synthes, for which royalties are received. No other potential conflict of interest relevant to In general, virtually all people have some degree this article was reported. of cervical degeneration with age, including in- Disclosure forms provided by the author are available with the full text of this article at NEJM.org. tervertebral disk desiccation, neural foraminal I thank Dr. Ethan Cottrill for assistance with the literature narrowing, osteophyte formation, and facet joint review and preparation of an earlier version of the manuscript.

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