Traumatic brain injury (TBI) is one of the more common neurological disorders. The incidence is estimated to be 101 per 100,000 for severe injuries and 540 per 100,000 for mild injuries. Because many patients with TBI are young, and almost all survive, the prevalence is very high—approximately 2% of the U.S. population has some TBI-related disability. The great majority of injuries are mild and recovery is the rule, so the prevalence of symptomatic patients is surely much lower, but not known with certainty. TBI can occur at any age. The common mechanisms of injury differ at different ages: motor vehicle accidents at all ages; accidents and abuse in young children; accidents and sports in school-age children and young adults; and falls in the elderly. Age and mechanism interact to affect outcome. Falls in the elderly have a poorer overall prognosis than other combinations. TBI is often due to alcohol-related accidents.

Various mechanisms of injury may produce different profiles of neuropathology, but rapid deceleration is common to most. The skull stops suddenly, but the brain continues to move within the skull. Those parts of the brain tightly tethered to the skull and adjacent to the falx—the venous sinuses and the large basal arteries—probably stop with the skull. Other regions less tightly tethered—particularly the frontal poles, the temporal poles, and the cerebellar hemispheres—may continue to move. The distances are very small but the times are very brief, so deceleration may produce substantial g-forces. Rotational forces produce more injury than purely translational forces.

Deceleration creates gradients of movement or potential movement within the brain, and these gradients generate shearing forces that damage fragile structures—axons and small blood vessels. Rotational gradients are the dominant force. This injury is called diffuse axonal injury (DAI). It is maximal in the frontal and anterior temporal white matter, distributed centripetally from the cortical-white matter boundary into the deeper white matter. Axons are not literally sheared, but the force disrupts function; membrane stability, intracellular transport, and metabolic integrity are all affected. If damaged near the cell body, the nerve may die (apoptosis). Small blood vessels may be damaged enough to leak, contributing to cerebral edema and even small hemorrhages, usually in white matter. The severity of DAI may vary from only transiently interrupted axonal function to severe structural injury, extensive cell death, and multifocal hemorrhages. Concussion is the mildest end of DAI. Based on animal experiments it remains unclear whether a single concussion is often or ever associated with structural brain injury. At a minimum, however, in both concussions and more definitive but mild TBI, there is some injury to axons that can be detected on late diffusion tensor imaging magnetic resonance imaging (DTI MRI) as regional reduction in fractional anisotropy. There is a period of altered cortical function demonstrated on functional MRI (fMRI) by abnormal patterns of activation during working memory tasks.

The same deceleration forces can propel portions of the cortex over rough, bony surfaces. The orbital frontal cortex and temporal poles are particularly susceptible. This injury is focal cortical contusion (FCC). The location of FCC may also be affected by skull deformation at the point of contact (coup) or opposite that point (contrecoup), but brain movement and irregular bony surfaces are the key elements of cortical deformation because anterior contusions are much more common than occipital contusions. In addition, depressed skull fractures can produce FCC underlying a fracture wherever it occurs, although fractures may actually absorb force and reduce brain injury. TBI may result in FCC in patients who otherwise appear to have a mild injury (defined blow), but the presence of FCC customarily excludes a patient from a diagnosis of mild TBI or concussion.

Patients with head injuries may also have subdural hematoma (SDH) or epidural hematoma (EDH). SDHs are commonly associated with subjacent FCC in young people, but in the elderly may occur without direct brain injury. If so, and if properly managed, there need be no brain consequence to the SDH alone. EDHs are usually caused by a fracture across the middle meningeal artery. They are extracerebral and, if recognized and evacuated, do not produce brain injury. Either EDH or SDH may, however, be sufficiently large that it causes underlying compression, vascular compromise (ischemia), and local edema. If very large, particularly if accompanied by FCC and edema, they may lead to increased intracranial pressure (ICP) and even cerebral herniation. These add local and even global hypoperfusion and ischemic injury into the TBI mix. These factors are the main mechanisms of delayed deterioration after TBI.