Concussions and other forms of traumatic brain injury (TBI) are hardly unknown in the world of sports. Until recently, however, reports of associations between TBI and later-onset neurodegenerative disease were anecdotal, and causation remained unproven. New research is now revealing the cumulative impact of multiple neurologic insults in young people. These investigations have suggested that, compared with healthy people, athletes who suffer multiple brain injuries as young adults may be at increased risk of serious neurologic disorders (such as Alzheimer’s disease [AD], Parkinson’s disease [PD], and amyotrophic lateral sclerosis [ALS]) later in adulthood.

TBIs can occur when forces are applied to the head during sports-related activities. The neurologic sequelae of such injuries have been the focus of increasing attention in recent years. Of particular interest has been the growing recognition that neuropathologic consequences of TBI may manifest years after the index events. Even though the situations under which the brain can suffer traumatic damage are varied and multifaceted, the mechanisms by which such injury occurs are beginning to be elucidated.

Classifications of TBI are shown in Table 1. Primary TBI (such as diffuse axonal or vascular damage) is induced by mechanical forces and occurs at the moment of injury.¹ Secondary TBI (such as hypoxia-ischemia and edema) is superimposed on a brain that has already been injured via a mechanical insult.¹

The types of brain damage occurring in TBI are classified as either focal or diffuse (ie, multifocal; Table 2).¹ Focal injury results from the forces of head acceleration and contact caused by direct blunt trauma.² Diffuse injury results from the inertial effects of either a mechanical blow to the head or of the acceleration and deceleration caused by a blow or a fall.² Although a combination of factors may be involved in any individual occurrence of TBI, focal damage generally results from a fall, whereas diffuse damage usually results from acceleration/deceleration.¹

The initial characteristics of a TBI reflect the distribution of the energy applied to the head.² As noted, the 2 major mechanisms of TBI are contact and acceleration/deceleration. ³ (Of note are recent data from Taylor et al⁴ gathered by simulations of explosive blasts, such as those encountered by soldiers and civilians during war, that suggest that TBI from blast exposure and blunt impact can also be caused by focal developments of stress and strain energy induced by early-time wave interactions that occur prior to the linear or rotational accelerations normally attributed to TBI.) Brain injuries due to contact tend to result from either an object striking the head or contact between the brain and skull.¹ Brain injury due to acceleration or deceleration results from unrestricted movement that leads to shear, tensile, or compression strain.¹

Much of the morbidity and mortality associated with TBI is caused by diffuse axonal injury (DAI), which results from dynamic deformations due to linear and rotational acceleration.^4,5,6 This type of injury involves a multifocal process that may be pervasive throughout the white matter tracts and other areas of the brain.⁷ The pathology of DAI is characterized by cytoskeletal disruptions, alterations in membrane permeability, the potential for axonal transections, and axonal swelling.^8,9 Although older concepts held that severed axons observed after TBI were the result of mechanical shearing or tearing, newer research has shown that most axonal transections reflect a progressive sequence of self-destruction following the initial trauma.^4,8,9,10 Despite the fact that the axon is injured by the trauma, initially it remains in continuity; subsequently, however, over a period of at least several hours, the axon fails at 1 or more foci and disconnects.² The pathologic process in the injured axon is believed to involve loss of homeostatic mechanisms responsible for maintaining the differential ionic gradients needed for normal electrical activity.² Axonal failure is followed by reactive swelling.¹¹