Neuropathological findings in disabled survivors of a head injury.

We investigated how the occurrence and severity of the main neuropathological types of traumatic brain injury (TBI) influenced the severity of disability after a head injury. Eighty-five victims, each of whom had lived at least a month after a head injury but then died, were studied. Judged by the Glasgow Outcome Scale (GOS), before death 35 were vegetative, 30 were severely and 20 were moderately disabled. Neuropathological assessment showed that 71 (84%) victims had sustained cerebral contusions, 49 (58%) had diffuse axonal injury (DAI), 57 (67%), had ischemic brain damage (IBD), 58 (68%) had symmetrical ventricular enlargement, and in 47 (55%) intracranial pressure (ICP) had been increased. Thirty-five (41%) had undergone evacuation of an intracranial hematoma. Brainstem damage was seen in only 11 (13%). Analysis (χ(2) test for trends) of the relationship between these features and outcome showed that findings of DAI, raised ICP, thalamic damage, or ventricular enlargement (all p<0.005), and IBD (p=0.04) were associated with an increasingly worse outcome. Conversely, moderate or severe contusions (p=0.001) were increasingly associated with better outcomes, and evacuation of a hematoma was associated (p=0.001) with outcomes likely to be better than vegetative. We conclude that diffuse or multifocal neuropathological patterns of TBI from primary axonal injury or secondary ischemic damage are most likely to be associated with the most severely impaired outcomes after a head injury.

Novel aspects of the neuropathology of the vegetative state after blunt head injury.

A detailed neuropathological study was undertaken of the brains of patients who had been assessed clinically as vegetative after blunt head injury. There were 35 cases, (33 male; median age 38 years) with a survival of 6.5-19 months (median 9): 17 were injured in a road traffic accident, 9 after assault and 6 after a fall; 3 were recorded as having had a lucid interval. There was an intracranial hematoma in 9 and the median contusion index was 4; raised intracranial pressure was identified in 25, grades 2 and 3 diffuse traumatic axonal injury was present in 25, ischemic damage in 15 and hydrocephalus in 27. Thalamic and hippocampal damage was present in 28 and stereological studies revealed a differential loss of neurons in three principal nuclei of the thalamus and in different sectors of the hippocampus. Immunohistochemistry provided evidence of an inflammatory reaction and in situ DNA fragmentation, features that are strongly indicative of a continuing neuronal loss in subcortical gray matter. These findings provide evidence for the importance of diffuse brain damage to white matter as the structural basis of the vegetative state after blunt head injury with contributions from neuronal loss in the thalami and the hippocampus. Although amyloid plaques and tau inclusions were identified in some, their contribution did not seem important in the ultimate clinical outcome.

Thirty years of the vegetative state: clinical, ethical and legal problems.

The vegetative state is the rarest form of disability in patients now frequently rescued from life-threatening severe brain damage by resuscitation and intensive care. Many doctors have never seen such cases, yet it provokes great interest among professionals and the public because of the paradox of a person who is awake yet not aware. The commonest cause is head injury and it is more common in countries with a high incidence of severe head injury. The most consistent brain damage is in the subcortical white matter of the cerebral hemispheres and in the thalami; although the cerebral cortex is often severely damaged, it may be relatively spared. Diagnosis depends on prolonged expert observation to determine that there is no evidence of awareness in spite of a wide range of reflex responses, some of which may involve cortical activity. Functional imaging confirms that there is some residual cortical function in many vegetative patients. Mistaken diagnosis is less likely since the recent definition of clinical criteria for the vegetative state and for the minimally conscious state. Many patients recover consciousness and even regain independence after a month in a vegetative state after head injury, but few do so after non-traumatic insult. The longer the state persists the less likely the recovery, and eventually permanence can be declared. Patients can survive for many years in a vegetative state. Many consider that indefinite survival in a vegetative state is of no benefit to the patient and that there is no moral or legal obligation to continue life-sustaining treatment, including artificial nutrition and hydration. Ethical issues include how to respect the autonomy of the legally incompetent patient, and uphold the right to refuse unwanted treatment. Many cases have been brought to court in several North American, Northern European and some other jurisdictions where it has been ruled that it is legally permissible to withdraw life-sustaining treatment once a patient is declared permanently vegetative, and such withdrawal seems likely to be what that person would want done.