SCI is associated with severe physical, psychological, social, and economic burdens on patients and their families. With an annual incidence rate of 15 to 40 persons per million, it has been estimated that at least 10,000 to 15,000 North Americans will suffer a SCI each year (2). With the average acute-care and rehabilitation charges of approximately $60,000.00 for each of these phases of care, the societal expense associated with the medical management, as well as lost earnings of this disorder over the course of one’s life is significant (3). Besides the economic burden, it is important to consider the severe psychological challenge for the patients and their families. For this and many other reasons, SCI has been considered a major public health problem. It has been estimated that the lifetime cost of medical care and other injury-related expenses for a 25-year-old patient with SCI who suffers a high cervical quadriplegia to be approximately $3 million (4). SCI predominantly occurs in young, otherwise healthy individuals, with injury occurring with the greatest frequency in those between 15 and 25 years of age; the male-to-female ratio for SCI is approximately 4 to 1 (5) Common causes of SCI in the United States are motor vehicle accidents (50%), falls and work-related injuries (30%), violent crime (11%), and sports-related injuries (9%) (6). Injuries most commonly occur in the cervical spine, and are associated with the most devastating neurologic impairments (e.g., quadriplegia). A recent report from the US National Spinal Cord Injury Database found that 56% of all SCI cases occur in the cervical spine.

A detailed understanding of the pathophysiologic processes occurring following SCI is paramount to the development of effective therapies for SCI. The pathophysiology of SCI is best described as biphasic, consisting of a primary and secondary phase of injury (7). The primary phase involves the initial, immediate mechanical injury during which failure of the spinal column occurs, and includes compression, contusion, shear, or laceration due to penetrating injury, and acute stretching of the spinal cord as a result of vertebral distraction or sudden acceleration-deceleration of the spinal column. The most common underlying primary injury mechanism results from the acute compression and contusion of the spinal cord due to bone or disk displacement within the spinal column during fracture dislocation or burst fracture of the spine (2). Multiple mechanisms of injury exist, which include damage to the spinal cord from direct trauma, compression (from bony fragments, hematoma, or disk material), and ischemia related to
damage or impingement on the spinal arteries. The primary mechanical trauma to the spinal cord, along with subsequent persistent compression, triggers a complex and delayed pathologic cascade, termed the “secondary injury” phase, which involves vascular dysfunction, edema, ischemia, excitotoxicity, electrolyte shifts, free radical production, inflammation, and delayed apoptotic cell death (8). Although neurologic deficits are present immediately following the initial injury, the secondary injury phase results in a protracted period of neuroinflammation and tissue destruction. The spatial extent of secondary injury events spreads both radially and longitudinally along the spinal cord in a rostral-caudal manner, resulting in neuronal and glial cell death. The end result is cavitation of central gray matter, along with partial or complete loss of adjacent white matter tracts.

The pathophysiology of SCI has been extensively studied in many experimental animal models, including mice, rats, cats, and primates, in order to understand the cellular and molecular mechanisms of tissue damage and the consequent disability (2). Traumatic SCI initiates a series of destructive cellular inflammatory processes that accentuate tissue damage at and beyond the original site of trauma, and cystic cavitation inevitably occurs due to these secondary injury events. Contusion SCI in animals produces a predictable pattern of progressive injury resulting in neuronal and glial cell death, vascular injury, axonal destruction, and demyelination, which is analogous to the human spinal cord contusion injury, the most common type of the human SCI (Fig. 53.1) (7,9). The progressive expansion of the injury from gray to white matter causes secondary damage to initially intact axons within hours to several weeks after injury. The cellular inflammatory response, predominated by macrophages, has been implicated as the primary mediator of progressive secondary injury. The major targets for spinal cord repair include severed and/or demyelinated axons, inflammatory cells and proinflammatory cytokines, and glial scar components.