Traumatic coma was produced in 45 monkeys by accelerating the head without impact in one of three directions. The duration of coma, degree of neurological impairment, and amount of diffuse axonal injury (DAI) in the brain were directly related to the amount of coronal head motion used. Coma of less than 15 minutes (concussion) occurred in 11 of 13 animals subjected to sagittal head motion, in 2 of 6 animals with oblique head motion, and in 2 of 26 animals with full lateral head motion. All 15 concussioned animals had good recovery, and none had DAI. Conversely, coma lasting more than 6 hours occurred in one of the sagittal or oblique injury groups but was present in 20 of the laterally injured animals, all of which were severely disabled afterward. All laterally injured animals had a degree of DAI similar to that found in severe human head injury. Coma lasting 16 minutes to 6 hours occurred in 2 of 13 of the sagittal group, 4 of 6 in the oblique group, and 4 of 26 in the lateral group, these animals had less neurological disability and less DAI than when coma lasted longer than 6 hours. These experimental findings duplicate the spectrum of traumatic coma seen in human beings and include axonal damage identical to that seen in sever head injury in humans. Since the amount of DAI was directly proportional to the severity of injury (duration of coma and quality of outcome), we conclude that axonal damage produced by coronal head acceleration is a major cause of prolonged traumatic coma and its sequelae.

Diffuse axonal injury is one of the most important types of brain damage that can occur as a result of non-missile head injury, and it may be very difficult to diagnose post mortem unless the pathologist knows precisely what he is looking for. Increasing experience with fatal non-missile head injury in man has allowed the identification of three grades of diffuse axonal injury. In grade 1 there is histological evidence of axonal injury in the white matter of the cerebral hemispheres, the corpus callosum, the brain stem and, less commonly, the cerebellum; in grade 2 there is also a focal lesion in the corpus callosum; and in grade 3 there is in addition a focal lesion in the dorsolateral quadrant or quadrants of the rostral brain stem. The focal lesions can often only be identified microscopically. Diffuse axonal injury was identified in 122 of a series of 434 fatal non-missile head injuries--10 grade 1, 29 grade 2 and 83 grade 3. In 24 of these cases the diagnosis could not have been made without microscopical examination, while in a further 31 microscopical examination was required to establish its severity.

Forty-five cases of diffuse axonal injury (DAI) brought about by nonmissile head injury in humans are analyzed and compared with 132 cases of fatal head injury without DAI. All cases were subjected to a comprehensive neuropathological study. In the patients with DAI a statistically significant lower incidence of lucid interval, fracture of the skull, cerebral contusions, intracranial hematoma, and evidence of high intracranial pressure were found, with a higher incidence of head injury due to road traffic accident. Brain swelling and hypoxic brain damage were not statistically different in the two groups. The features of DAI in humans are compared with the DAI that has been produced in subhuman primates by pure inertial loading brought about by angular acceleration of the head. The available evidence indicates that DAI in human beings occurs at the time of head injury and is not due to complicating factors such as hypoxia, brain swelling, or raised intracranial pressure.

The vegetative state is often described clinically as loss of function of the cortex while the function of the brainstem is preserved. In an attempt to define the structural basis of the vegetative state we have undertaken a detailed neuropathological study of the brains of 49 patients who remained vegetative until death, 1 month to 8 years after an acute brain insult. Of these, 35 had sustained a blunt head injury and 14 some type of acute non-traumatic brain damage. In the traumatic cases the commonest structural abnormalities identified were grades 2 and 3 diffuse axonal injury (25 cases, 71%). The thalamus was abnormal in 28 cases (80%), and in 96% of the cases who survived for more than 3 months. Other abnormalities included ischaemic damage in the neocortex (13 cases, 37%) and intracranial haematoma (nine cases, 26%). In the non-traumatic cases there was diffuse ischaemic damage in the neocortex in nine cases (64%) and focal damage in four (29%); the thalamus was abnormal in every case. There were cases in both groups where the cerebral cortex, the cerebellum and the brainstem were of structurally normal appearance. In every case, however, there was profound damage to the subcortical white matter or to the major relay nuclei of the thalamus, or both. These lesions render any structurally intact cortex unable to function because connections between different cortical areas via the thalamic nuclei are no longer functional, and there is also extensive damage to afferent and efferent cerebral connections.

SUMMARY A detailed neuropathological examination has been undertaken on a consecutive series of head injuries dying in the Institute of Neurological Sciences, Glasgow, between 1968-72 (151 cases) and 1981-82 (112 cases)