Concussion refers to an immediate, usually reversible episode of brain dysfunction after TBI. A clinical spectrum is recognized ranging from mild concussion, in which consciousness is often preserved, to severe diffuse traumatic axonal injury resulting in the vegetative state (Gennarelli 1993). The anatomical basis of concussion syndromes is currently considered to be traumatic axonal pathology and, in particular, axonal disruption resulting in disconnection between areas involved in consciousness: cerebral cortex, brainstem reticular activating areas, thalamus, and hypothalamus. Patients in a vegetative state refers to patients who have loss of meaningful cognitive function and awareness but retain spontaneous breathing and periods of wakefulness. The neuropathological basis of the vegetative state has been explored in a study that examined 49 patients in a vegetative state, 35 of whom had experienced TBI (Adams et al. 2000). In the trauma-related cases, diffuse traumatic axonal injury of grade 2 or 3 was found in 71% of cases, and thalamic pathology was found in 80% of cases. In cases with minimal brainstem and cerebral cortical pathology, thalamic pathology was always present. Therefore, damage to the thalamic nuclei and/or the afferent and efferent white matter pathways of the thalamus appear to play a major role in the genesis of the vegetative state after head injury. The thalamic nuclei showed differing degrees of loss, with cognitive and executive function nuclei being most severely affected (Maxwell et al. 2006). White matter (Wallerian) degeneration is a consequence of severe diffuse traumatic axonal injury. The axonal loss results in gliosis and macrophage activation, which may be under genetic control, as discussed later. In contrast, the structural basis of moderate disability after TBI is more likely to be a focal lesion rather than diffuse brain pathology, usually an evacuated intracranial hematoma (Adams et al. 2001). In a study of 30 patients with severe disability, 50% had focal brain pathology only. Some severely disabled patients did show diffuse brain pathology similar to vegetative state patients, and it may be that there is a greater quantitative amount of damage in the vegetative cases. In assessment of the pathology of moderate and severe disability, case selection may be important, and it must be remembered that autopsy-based studies may not be a true reflection of the clinical spectrum associated with both moderate and severe disability.