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This study is a combination of narrative and systematic review.Clinicians who deal with cervical spondylotic myelopathy (CSM) should be up-to-date with the emerging knowledge related to the cascade of pathobiological secondary events that take place under chronic cervical spinal cord compression. Moreover, by performing a systematic review, we aim to (1) describe the natural history and (2) determine potential risk factors that affect the progression of CSM.The pathophysiology, natural history, as well as the factors associated with clinical deterioration have not been fully described in CSM.For the first part of the study, a literature review was performed. To answer key questions 1 and 2 of the second goal, a systematic search was conducted in PubMed and the Cochrane Collaboration Library for articles published between January 1, 1956, and November 7, 2012. We included all articles that described the progression and outcomes of CSM for which no surgical intervention was given.By performing a narrative literature review, we found that the assumption that acute traumatic spinal cord injury and CSM share a similar series of cellular and molecular secondary injury events was made in the past. However, recent advances in basic research have shown that the chronic mechanical compression results in secondary injury mechanisms that have distinct characteristics regarding the nature and the temporal profile compared with those of spinal cord injury. For the purpose of the systematic review, 10 studies yielding 16 publications met inclusion criteria for key questions 2 and 3. Moderate-strength evidence related to the natural history of CSM suggests that 20% to 60% of patients will deteriorate neurologically over time without surgical intervention. Finally, there is low-strength evidence indicating that the area of circumferential compression is associated with deteriorating neurological symptoms.CSM has unique pathobiological mechanisms that mainly remain unexplored. Although the natural history of CSM can be mixed, surgical intervention eliminates the chances of the neurological deterioration.Evidence-Based Clinical Recommendations.Recommendation. Evidence concerning the natural history of CSM suggests that 20% to 60% of patients will deteriorate neurologically over time without surgical intervention. Therefore, we recommend that patients with mild CSM be counseled regarding the natural history of CSM and have the option of surgical decompression explained.Overall Strength of Evidence. ModerateStrength of Recommendation. StrongSummary Statements. Chronic compression of the spinal cord results in progressive neural cell loss related to secondary mechanisms including apoptosis, neuroinflammation, and vascular disruption.