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 Neurosurgery, 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 neck pain 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 osteoarthritis, and neck arthritis. The term spondylosis comes from the Greek word spóndylos, meaning vertebra. 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 neck pain, mechanical or axial neck pain, compression and inflammation of the cervical nerve roots exiting the cervical spine (cervical radiculopathy), and compression and inflammation of the adjacent cervical spinal cord (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 n engl j med 383;2 nejm.org July 9, 2020 159 The New England Journal of Medicine Downloaded from nejm.org at CMU LIBRARIES - library.cmich.edu on July 8, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved. The new england journal of medicine 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- Myelopathy occurs if vertebral bodies are dis- ing catabolic processes within the intervertebral placed, a condition termed spondylolisthesis.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 facet joint syndrome, which is combination of increased load sharing by the focal pain caused by degeneration of a cervical 160 n engl j med 383;2 nejm.org July 9, 2020 The New England Journal of Medicine Downloaded from nejm.org at CMU LIBRARIES - library.cmich.edu on July 8, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved. Degenerative Cervical Spondylosis 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