The Neuropathological Basis of a Poor Outcome After Non-Missile Head Injury

The main purpose of this thesis was to identify the pathological processes underlying a poor outcome after non-missile head injury. To achieve this, comprehensive neuropathological studies were undertaken in a postmortem series of 48 fatal cases of non-missile head injury who had survived more than one month and were classified as comatose, vegetative or severely disabled. There had been a fracture of the skull in 26 cases (54%). Cerebral contusions were present in 43 cases (90%). Contusions were quantified by the "contusion index" method and their anatomical distribution and relationship to other lesions examined. Intracranial haematomas had been present in 26 cases (54%) and had been evacuated neurosurgically in 21 cases (44%). Diffuse axonal injury was present in 25 cases (52%) and was the most common finding apart from cerebral contusions. Focal lesions in the corpus callosum and rostral brain stem occurring in cases of diffuse axonal injury were analysed and formed the basis of a method for grading the severity of diffuse axonal injury. Diffuse axonal injury was shown to be associated with various lesions apparently of vascular origin, including sulcal infarcts, gliding contusions and other parenchymal lesions. It is suggested that these features are manifestations of "diffuse vascular injury". There was evidence of a previously high intracranial pressure, in the form of pressure necrosis in one or both parahippocampal gyri, in 28 cases (58%). Lesions in the brain stem due to a high intracranial pressure were considered to be present in 14 cases (29%). In 8 of these the lesions were large and took the form of a haematoma or infarcts. In the other 6 cases, however, the secondary lesions could only be detected microscopically and comprised minute infarcts or foci of gliosis. Brain damage of hypoxic or ischaemic origin was present in 27 cases (56%). This was diffuse in 2 cases, of boundary-zone distribution in 5 cases, and occurred within main arterial territories or in the region of the basal ganglia in the remaining 20 cases. Diffuse axonal injury, cerebral contusions, hypoxic/ ischaemic brain damage and secondary lesions in the brain stem were thus identified as the principal types of structural damage. There was considerable overlap since there was more than one type of lesion in 40 cases. One type of lesion only was found in 8 cases, but in no case was a secondary lesion in the brain stem the only type of lesion present. Four main categories of structural damage were identified as contributing most to the clinical outcome. These were: diffuse axonal injury in 25 cases (52%); hypoxic/ ischaemic brain damage in 11 cases (23%); a combination of a macroscopic secondary lesion in the brain stem and hypoxic/ ischaemic brain damage in 8 cases (17%); and, cerebral contusions in 4 cases (8%). There was a relationship between the grade of diffuse axonal injury and the clinical outcome. Diffuse axonal injury was the most frequent cause of a vegetative state (68% of cases). A macroscopic secondary lesion in the brain stem together with hypoxic/ischaemic brain damage was the most common finding in cases of prolonged coma (50% of cases), and hypoxic/ischaemic brain damage was the most common cause of severe disability (44% of cases). Diffuse axonal injury was the next most frequent cause of both prolonged coma (33% of cases) and severe disability (38% of cases). Diffuse axonal injury was thus found to be the most common cause of a poor outcome after non-missile head injury. Ventricular enlargement was quantified by a point-counting method. Hydrocephalus was deemed to be present in 65% of cases assessed. In general there was a relationship between the size of the ventricles and duration of survival. Apart from one patient of long survival who died as a result of a cerebellar haematoma, a definite cause of obstructive hydrocephalus or evidence of a terminally high intracranial pressure was not found in any case although one patient had been treated clinically for obstructive hydrocephalus. Cerebral atrophy appeared to be the most important factor leading to ventricular dilatation. Some complications of late onset were identified. These comprised cerebrovascular disease, central pontine myelinolysis associated with Marchiafava-Bignami disease, and pellagra