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The pathophysiology and biological mechanisms of cervical spondylotic myelopathy
Institution:1. Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD;2. Department of Orthopedics, Georgetown University School of Medicine, Washington, DC;1. Combined Massachusetts General Hospital/Brigham and Women''s Hospital, Orthopaedic Spine Surgery Fellowship, Boston, MA;2. Orthopaedic Spine Service, Brigham and Women''s Hospital, 75 Francis Street, Boston, MA 02115;3. Harvard Medical School, Boston, MA;1. Cleveland Clinic Center for Spine Health, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA;2. Case Western Reserve University School of Medicine, 2109 Adelbert Rd, Cleveland, OH 44106, USA;3. Cleveland Clinic Lerner College of Medicine, 9500 Euclid Ave., Cleveland, OH 44195, USA;4. Department of Quantitative Health Sciences, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA;5. Neurological Center for Pain, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA;6. Carolina Neurosurgery & Spine Associates, 225 Baldwin Ave, Charlotte, NC 28204, USA;7. Department of Neurological Surgery, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA;1. Department of Nephrology, Kartal Research and Training Hospital, Istanbul, Turkey;2. Department of Transplantation, Kartal Research and Training Hospital, Istanbul, Turkey;3. Department of Immunology, Bilim University, Istanbul, Turkey
Abstract:Cervical spondylotic myelopathy (CSM) is a common degenerative disease of the spine that is the direct result of spinal cord compression. With age, the spine undergoes natural degenerative changes that can affect its basic anatomy and lead to stenosis of the spinal canal. Various pathologies involving the vertebrae, intervertebral discs, facet joints, and ligaments of the vertebral column can all contribute to the manifestation of this disease and can be categorized into either static or dynamic mechanisms. Of the static mechanisms, degeneration of the intervertebral discs is one of the most characteristic processes associated with CSM. The formation of osteophytes, ossification of the posterior longitudinal ligament (OPLL), ossification of the ligamentum flavum (OLF), and a genetic predisposition to have a tightened spinal canal are also static pathologies that can contribute to the presentation of myelopathic symptoms in patients. Dynamic mechanisms primarily involve excessive motion of the cervical spine due to traumatic injuries, such as motor vehicle collisions. On a macroscopic level, damage to blood vessels and soft tissue can occur due to the previously described mechanisms; however, on a microscopic level, the pressure from constant spinal cord compression can result in ischemia, an underlying mechanism of CSM and the primary molecular cause of the disease. When the neurons of the spinal cord are deprived of oxygen and essential nutrients due to compression, they initiate an irreversible apoptotic cascade in the affected tissue. This molecular sequence of events is believed to target oligodendrocytes and cause the demyelination of adjacent neurons. As oligodendrocytes die, chronic demyelination of the neurons in the spinal cord occurs, causing residual or even permanent nerve damage after surgical decompression. The exact molecular pathway that results in the debilitating symptoms associated with this disease is not yet fully understood. A better understanding of both the biologic and mechanical mechanisms that cause CSM will significantly improve physicians׳ ability to treat patients diagnosed with this disease and decrease the prevalence of patients suffering from spinal cord impairment.
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