Consciousness has been defined in its most simple terms as awareness of the self and the environment. Putting aside the numerous philosophical views of consciousness, for the neurologist, normal consciousness requires both arousal via the ascending reticular activating system of the pons, posterior hypothalamus, and thalamus, and awareness via the neurons of the cerebral cortex and their projections to and from the subcortical nuclei. Wakefulness is, of course, required for awareness, but wakefulness may occur without the presence of awareness. Coma is a condition of deep pathologic unconsciousness in which there is no arousal and the eyes remain closed despite stimulation. (Coma is discussed throughout several chapters of this book in relation to specific disease processes.) As compared to the unconsciousness of the comatose patient who is not awake, the patient in a vegetative state is wakeful but lacks awareness. Of course, there is some “biologic limitation to the certainty of this definition, since we can only infer the presence or absence of conscious experience in another person” (2). A minimally conscious state also has been described wherein some evidence of awareness is found that precludes a diagnosis of vegetative state (3). The minimally conscious state may be considered to be part of a continuum following coma and vegetative state with perhaps a slightly higher likelihood of improvement to a fully conscious state. Brain death is irreversible coma and apnea with the permanent absence of all brain function, including the brainstem.

Although well known to neurologists and neurosurgeons, several definitions bear clarification. The vegetative state is defined as a complete unawareness of self (presumed) and the environment (as observed by reactions to various stimuli) (2,4, 5 and 6). Sleep-wake cycles usually are preserved, even if in rudimentary form, and there is at least partial preservation of the autonomic functions of the hypothalamus
and brainstem. There should be no evidence of reproducible voluntary responses to any sensory stimuli. There is no language expression or comprehension. Sustained visual pursuit is usually absent and there is no fixation or tracking of an object, although there may be some inconsistent reflexive turning of the head or eyes toward a visual or auditory stimulus. The vegetative state almost always follows an initial period of coma lasting for days to weeks. For the vegetative state to be described as persistent, it has been suggested by several authors that it should be present for at least 1 month. If there is any evidence of voluntary responses to sensory stimuli, the diagnosis of vegetative state should not be used, and perhaps “minimally conscious state” would be a better term (3). Patients with ambiguous or inconsistent responses to sensory stimuli are not uncommon in our experience if sought by careful examination and some of them progress from an apparent vegetative state to the severe dementia of the newly defined minimally conscious state. If consciousness is fully preserved but the patient is immobile, the patient may be in a locked-in state. The locked-in syndrome generally occurs in the setting of a pontine stroke with sparing of vertical eye movements and lid elevation that are used to indicate responsiveness, but may also occur in other conditions such as severe Guillain—Barré syndrome. The clinical setting and communication through eye movement or other limited signals readily distinguishes the locked-in syndrome from the vegetative state.

Electroencephalography (EEG) of a persistently vegetative patient usually shows diffuse polymorphic delta or theta activity not affected by sensory stimulation (7). Positron emission tomography (PET) shows reduced cerebral glucose metabolism by more than 50% compared with normal and locked-in patients but comparable to normal patients during
deep general anesthesia (2,8). Whether this pattern of cerebral blood flow and metabolism can be used as a defining or diagnostic feature of the vegetative state, as indicated by several authoritative authors in the field, is not clear to us. Pathologic findings may include diffuse cortical laminar necrosis, infarcts in the hypothalamus or brainstem and, in the case of trauma, diffuse subcortical and brainstem axonal injury (2). Perhaps the most surprising aspect, concordant with our own examinations, is the high frequency of bilateral thalamic damage rather than diffuse cortical damage as the main pathologic change after both traumatic injury and ischemic-anoxic injury, as in the much-discussed case of Karen Quinlan (9). Premortem magnetic resonance imaging may or may not demonstrate some of these pathologic findings (Fig. 9.1A,B).

A number of factors in a comatose patient have been predictive of a vegetative outcome. After a traumatic brain injury, older age, ventilatory failure, and decorticate posturing have been associated with a poor outcome (10). Coma from a nontraumatic cause generally has a worse prognosis than coma from a traumatic cause. Impairment of eye opening, oculocephalic responses, and motor responses at 2 weeks after a nontraumatic brain injury is associated with a poor outcome (11). Bilateral absence of somatosensory evoked potentials 1 week after the injury is highly predictive of death or vegetative state. On the other hand, some patients with normal evoked potentials may remain in a vegetative state and some posttraumatic patients may recover slight cognitive activity despite absence of somatosensory evoked potentials (12). Prolongation of central conduction time of the somatosensory evoked response and brainstem auditory evoked potentials are not as useful predictors of poor prognosis (13). In one study of postanoxic coma, PET scanning demonstrated a 50% reduction in cerebral glucose metabolism in PVS patients compared with a 25% reduction in those who regained consciousness (14). An abnormal CT or MRI scan is more likely in PVS than in those who recover (15). There is currently not enough evidence, however, to use PET, CT, or MRI scanning for prognostication.

The prognosis for persistent vegetative state (PVS) depends in part on the etiology. The most common causes in both adults and children are head trauma and hypoxic ischemic encephalopathy (Table 9.1) (2,7). Recovery of consciousness from posttraumatic PVS is highly unlikely in an adult after 1 year. Recovery from nontraumatic PVS is unlikely after 3 months. There are, of course, exceptions but they are quite rare and the high degree of certainty of a poor prognosis should be conveyed to families of affected individuals. Young children, however, may do far better than predicted after many months of unresponsiveness. It can be said with confidence that patients that are vegetative secondary to a degenerative disease have a uniformly dismal prognosis (2). Most patients in PVS do not survive longer than 2 to 5 years. Death occurs from infection, generalized systemic failure, respiratory failure, and in some cases, sudden death of unknown etiology. It is also worth-while
noting, particularly in discussions with the family, that the Multi-Society Task Force on PVS reviewed the unusual cases of late recovery of consciousness from the literature and popular media reports and found that the total number of these patients was quite small considering the prevalence of PVS, and, perhaps more important, all were left with severe disability (2).

Management of the patient depends on accurate determination of diagnosis and prognosis. Decision-making issues regarding level of care for these patients are discussed in Chapter 23. The estimated prevalence of PVS in the United States is 10,000 to 25,000 adults and 4,000 to 10,000 children and total annual costs for the care of these patients are estimated to be between 1 and 7 billion dollars (2).

The Uniform Determination of Death Act allows that death can be diagnosed on a neurological basis, that is, brain death, in the United States (similar views are held elsewhere with minor modifications) but the United States Act does not delineate the specific criteria for the diagnosis (16). The main causes for brain death in adults are traumatic brain injury and subarachnoid hemorrhage, and in children are abuse, motor vehicle accidents, and asphyxia (17,18). Brain death generally occurs as the result of cerebral herniation with intracranial pressure simultaneously rising above mean arterial pressure and cerebral blood flow stopping.

Before performing an examination for brain death, certain confounding factors should be determined to be absent. Most important, the patient’s core temperature should be at least 33°C. In actuality, the likelihood of hypothermia simulating brain death at even slightly lower levels is unlikely but some limits should be set in order to avoid a false-positive diagnosis and the difficulty that such an error produces. The patient’s systolic blood pressure generally should be greater than 100 mm Hg, again, a somewhat arbitrary level but one on which there is general agreement. Certainly, entertaining the diagnosis of brain death when the blood pressure is substantially lower is tenuous. The cause and irreversibility of the coma should be known. Drug intoxication, especially with barbiturates, tricyclic an-tidepressants, or neuromuscular blocking agents should be ruled out by appropriate blood and urine testing, even if the source of brain injury is obvious, as in head trauma. The issue of admissible levels of therapeutic agents that may confound the neurological examination and EEG has not been satisfactorily resolved. We have taken the position that levels below those known to be soporific are acceptable but these have not been established for all barbiturate and sedative-like drugs and others have expressed the view that these drugs should be absent from the blood. There should be no significant electrolyte, acid-base, or endocrine abnormalities, but again, mild degrees of hypernatremia or hyponatremia and similar disturbances do not preclude the diagnosis. Severe metabolic abnormalities, such as hyponatremia or hypernatremia or hypophosphatemia should be corrected prior to determining brain death.

The clinical examination for brain death traditionally includes ascertainment of deep unresponsive coma, absence of brainstem reflexes, and apnea. The patient should be comatose with no responsiveness even to deep pain. Deep pain may be applied by sternal rub, supraorbital nerve compression, or nail bed pressure. There should be no eye opening or motor response present, including extensor or flexor posturing. This last item has also been a point of contention but well-formed posturing is not consistent with brain death because it most likely requires suprasegmental input from brainstem centers. Occasionally, a triple flexion response in the lower extremities or a brief flexion of the fingers may be elicited. Perhaps surprisingly, Babinski signs are uncommon in brain dead patients; instead a slow flexion and fanning of the toes is more frequent; however, there is no proscription of the diagnosis if a classic extensor toe sign is found (17,19, 20, 21, 22 and 23).