Diffuse axonal injury in non-missile head injury.

Brain damage brought about by a non-missile head injury takes two forms-focal and diffuse. ' The principal types of focal brain damage are contusions on the surface of the brain, intracranial haematoma and the various types of brain damage secondary to intracranial expanding lesions and a high intracranial pressure. In this era of sophisticated scanning, the clinician usually knows that lesions of this type are present during life, and their nature. Diffuse brain damage is more subtle and consists of axonal injury, hypoxic brain damage, brain swelling and vascular injury. The clinician usually suspects that diffuse brain damage is present when faced with an unconscious patient who does not have an intracranial haematoma. Although in the last decade computed tomography has played a very important role in the diagnostic evaluation of head injured patients, the advent of magnetic resonance imaging has been found to be particularly useful in the detection and classification of traumatic lesions in closed head injury2 but it may be very difficult to define the type ofdamage during life. It may also be difficult to define diffuse brain damage post mortem unless the brain is properly fixed before dissection and the appropriate histological studies are carried out. As a result of a comprehensive clinical study on head injuries carried out in the University of Pennsylvania, it became apparent that two lesions-acute subdural haematoma and diffuse axonal injury-were responsible for two thirds of the deaths, that is, more than all other lesions combined.3 It could, however, be argued that diffuse axonal injury (DAI) is of particular importance in governing the outcome in anyone who sustains a non-missile head injury. Certainly patients who sustain severe DAI are unconscious from the moment of injury, do not experience a lucid interval and remain unconscious, vegetative or at least severely disabled until they die. The first publication to focus attention on this type of brain damage was by Strich in 19564 when she described four cases of "diffuse degeneration of the cerebral white matter in severe dementia following head injury". The term "vegetative state"5 would amost certainly now be the term used to describe what Strich referred to as severe dementia. Other authors in the 1960s, particularly Nevin,6 and Peerless and Rewcastle,7 stressed the importance of damage to white matter in head injury. During this period the term "shearing" injury was introduced. Later this type of brain damage was referred to as diffuse damage to white matter of immediate impact type8 or diffuse white matter shearing injury.9 Currently the term DAI is used internationally to describe this type of brain damage. The structural features of DAI and their time course were reviewed and redefined by Adams and his associates in Glasgow in 198210 when they described a series of 45 fatal cases. In its most severe form, DAI has three distinctive structural features: a focal lesion in the corpus callosum; a focal lesion or lesions in the rostral brain stem; and diffuse damage to axons. The first two of these can often be identified macroscopically post mortem and increasingly by modern neuro-imaging techniques during life. "1 12 In patients of short survival the focal lesions are usually haemorrhagic but with the passage ofweeks or months they come to be represented by shrunken scars that may be difficult to identify at necropsy but they are often brown in colour because of the persistence of haemosiderin. The lesion in the corpus callosum typically occurs in its inferior part and to one side of the midline. It may, however, extend to the midline and, if this occurs, there is often disruption of the interventricular septum resulting frequently in some blood within the lateral ventricles. On occasion the splenium is particularly affected. In the rostral brain stem the lesions characteristically occur in the dorsolateral quadrant or quadrants adjacent to a superior cerebellar peduncle. The clinical state is not attributable to these focal lesions but to the diffuse damage to axons that accompanies them. This damage can be seen only on microscopical examination and takes three forms depending on the duration of survival. In patients of short (days) survival there are large numbers of axonal swellings in the white matter: they are not restricted to the corpus callosum and the dorsolateral quadrant of the rostral brain stem but occur throughout the cerebral hemispheres, the cerebellum and the brain stem. In patients of intermediate (weeks) survival, there are many small clusters of microglia throughout the white matter: these are thought to occur in relation to small tissue tears and degenerating axons. And in patients who survive for many months severely disabled or in the vegetative state the typical feature-as originally described by Strich4-is the occurrence of Wallerian-type degeneration in the white matter throughout the cerebral hemispheres, the brain stem and the spinal cord. If a patient with DAI survives for several months, there is progressive enlargement of the ventricular system as a result of loss of bulk of the white matter. By this stage the focal lesions may be very difficult to identify and unless the pathologist is acquainted with the entity of DAI he might think that he is simply faced with a case of post-traumatic hydrocephalus. The 45 cases described by Adams et al 10 were compared with a group of 112 fatal non-missile head injuries encountered over a similar period in the same centre but who did not have DAI. In the patients with DAI there was a statistically significant lower incidence of lucid interval (indeed not one of the patients with DAI in this series had experienced a lucid interval), fracture of the skull, cerebral contusions, intracranial haematoma and evidence of a high intracranial pressure. There was also a higher frequency of head injury due to road traffic accidents in comparison to falls. Brain swelling and hypoxic brain damage were not 481