Mechanisms of Traumatic Spinal Cord Injury AIS Grade Conversion

Spinal cord injury (SCI) remains a major unsolved problem that permanently impairs the lives of innumerable individuals worldwide. Although advances in the basic, pre-clinical and clinical sciences of SCI hold promise for patients, clinicians may lack a full insight into the relevant cellular and molecular events, and laboratory researchers may underappreciate how cellular and molecular phenomena translate into meaningful functional outcomes. To help bridge these perspectives, we first review the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, which is the principal instrument used to gauge clinical outcomes in SCI, and the clinically important concept of AIS grade "conversion" (improvement), which occurs in some but not all patients. We then review underlying mechanisms that contribute to the AIS grade and its conversion, including mechanisms of transient neurological dysfunction (neuronal and axonal "stunning"), mechanisms of secondary cell loss (apoptosis, pyroptosis, and necroptosis), and mechanisms of axonal loss (primary axotomy and secondary axonal degeneration). Finally, we briefly review approaches to clinical management that may ameliorate identified mechanisms of secondary tissue loss and neurological dysfunction following SCI.