CHAPTER 9 THE PERSISTENT VEGETATIVE STATE (PROLONGED POSTCOMA UNRESPONSIVENESS) AND POSTHYPOXIC BRAIN INJURY
Prolonged survival in a vegetative state is one of the most harrowing events encountered in modern medicine. Although the condition provides intellectual challenges to the expertise of medical ethicists, legal practitioners, and legislators, the patient’s family members and others intimately involved in the daily care of the patient are usually caught in a web of despair, unresolved grief, anger, a pervading sense of futility, and fading hope. Adversarial relationships between medical staff and family may arise, especially if iatrogenic issues such as anesthetic catastrophes are present. Family members may clutch at slim hopes offered by media reports of recovery after prolonged coma or vegetative states. Physicians may be torn by the conflict between limited resources and the pressure to persevere with intensive support, potentially restricting access to patients with substantially better chances of recovery. Decisions to continue or withdraw support are often charged with ethical and medicolegal implications, inasmuch as either course of action can be construed to be contrary to the “best interests” of the patient.
The various terms vegetative state (persistent and permanent) and postcoma unresponsiveness are used to describe the clinical emergence of the patient from deep coma to a state in which the sleep-wake cycle is reestablished but the patient shows no clinical evidence of cognitive interaction with the world around him or her. When the state is deemed to be unremitting (more than 3 months after anoxic brain damage* or more than 12 months after traumatic brain injury) the term permanent vegetative state is recommended. Expert groups in the United States1 and Europe have suggested using only the terms vegetative state and permanent vegetative state because the term persistent has become shrouded with ambiguity. The terms vegetative state and persistent vegetative state do not imply irreversibility; however, the term permanent vegetative state carries prognostic implications.
For the situation in which some minimal level of purposeful response to environmental stimuli is observed, the term minimally conscious state has been advocated.4 The terminological uses vary, and some authors5 have advocated avoiding the term vegetative in view of its potentially pejorative connotations, but the original description6 remains widely accepted.
CRITERIA
Vegetative State
The salient features of the vegetative state† are as follows:
The Minimally Conscious/Responsive State
Patients may improve from the vegetative state to demonstrate clearly discernible evidence of self or environmental awareness. The term minimally conscious state4 or minimally responsive state7 has been proposed to describe the condition of such patients. Minimal criteria such as the ability to follow a simple command, the presence of intelligible verbalization, or sustained visual following have been proposed to identify this state. Such responses may be intermittent and more easily evoked by family than by medical staff. Repeated observations may be necessary to distinguish this state from the vegetative state. Such purposeful responses clearly exclude a diagnosis of vegetative state, but difficulties defining the level of cognitive function sufficient to exceed a diagnosis of the minimally conscious state have limited widespread application of the term. The reestablishment of interactive communication, including orientation to place, the ability to give accurate autobiographical information, and the appropriate use of objects, are generally considered to indicate that the patient is functioning at a level higher than the minimally conscious state.
It is important to note that the lack of behavioral manifestations of self or external awareness cannot by themselves prove the absence of a residual or rudimentary subjective awareness. It may not be possible clinically to distinguish a minimally responsive patient with residual cognitive function from one who lacks adequate afferent processing or efferent control to reliably demonstrate understanding or performance of a requested task. Indeed, Owen and colleagues8 reported three patients with clinical diagnoses of persistent vegetative state who demonstrated “covert cognitive processing” in positron emission tomographic scanning with a facial recognition task. It is also conceivable that patients may satisfy the criteria for the minimally conscious state on a “good” day and, perhaps as a consequence of infection, electrolyte disturbance, or fatigue, show no sign of awareness on a “bad” day.9 Because of such patients, the boundary between the vegetative state and the minimally conscious state may not be as discontinuous as the definitions suggest.
Locked-In Syndrome
The locked-in syndrome refers to a state in which cognitive processing is clearly evident but severe paralysis prevents articulation or gestural expression of awareness. Communication may be achieved by encoding eyelid or ocular movement. In severe cases, the diagnosis may depend on the demonstration of a normal reactive alpha rhythm on the electroencephalogram (EEG).10 Such patients usually have isolated lesions of the ventral pons with preserved cerebral hemispheres. Locked-in syndrome may also occur as a consequence of severe peripheral nerve or muscle disease.
Akinetic Mutism
The term akinetic mutism has been used to describe a range of cases in which varying degrees of consciousness, paralysis, and mutism may be present. Various pathological findings have been described,11 including infarction of the anterior cingulate gyrus.12 Cairns and associates13 described an adolescent with a craniopharyngioma who developed repeated episodes of “silent immobility” with open and apparently attentive eyes and occasional whispered monosyllables whose state was reversed on several occasions by aspiration of the tumor. A similar case with improvement after shunting has been described more recently.14 Akinetic mutism has been divided into frontal and mesencephalic types, the latter distinguished by the presence of vertical gaze palsy or ophthalmoplegia. Cyclosporine neurotoxicity15 and baclofen toxicity16 may each cause a reversible state of akinetic mutism. Severe frontal abulia (for example, caused by bilateral anterior cerebral artery infarction or a ruptured anterior communicating aneurysm) may be impossible to distinguish on clinical criteria from either akinetic mutism or the minimally conscious state.
EPIDEMIOLOGY
The incidence and prevalence of vegetative state in the community vary widely in accordance with the sources of the data. A comprehensive review3 of the epidemiology of vegetative state revealed prevalence rates in the United States ranging from 24 to 168 per million of the population in studies dating from 1990 to 1994. The Multi-Society Task Force on Persistent Vegetative State (1994) accepted an estimate from Ashwal and colleagues17 of 56 to 140 per million.
The incidence of vegetative survivors after all acute causes at 1, 3, and 6 months has been estimated for the United Kingdom, the United States, and France.3 The incidence falls with time as patients either die or attain higher levels of function and is also heavily influenced by the level of head injury in the community. At 1 month after injury, the incidence ranges from 14 per million in the United Kingdom to 67 per million in France. By 6 months after the cerebral insult, the incidence of survival in a vegetative state is 5 per million in the United Kingdom, 17 per million in the United States, and 25 per million in France. The relative contribution of traumatic to nontraumatic causes of vegetative state also varies considerably, depending on the source of the data. Studies have shown the contribution of head injury ranging from 24%18 to 72%.1 Some studies include patients who decline into a vegetative state as a consequence of progressive neurodegenerative disorders, as opposed to progressing to a vegetative state from coma caused by an acute cerebral insult. This and other case ascertainment issues continue to complicate the epidemiological data.
PATHOLOGY
In the setting of cerebral anoxia or diffuse ischemia, there is usually extensive neocortical laminar necrosis and bilateral hippocampal, amygdalar, and thalamic damage.19,20 The Purkinje cell layer of the cerebellum is similarly vulnerable to diffuse ischemic injury. A second pattern of brain damage occurs after a short episode of profound hypotension, in which the ischemic damage is confined to the arterial boundary zones. This produces wedge-shaped zones of ischemia with additional bilateral thalamic damage and varying involvement of the hippocampus.
After severe traumatic brain injury, the brunt of the pathology is subcortical and conforms to the diffuse shearing injuries now known as diffuse axonal injury (DAI), as described by Strich in 195621 and 1961.22 DAI is graded into types I to III; grade I is defined as diffuse subcortical shearing injury without callosal or brainstem involvement, grade II indicates additional focal lesions in the corpus callosum, and grade III indicates additional lesions in both the corpus callosum and the dorsolateral region of the rostral brainstem. Patients with DAI grade I are unlikely to remain in a prolonged vegetative state unless there is coexisting evidence of a hypoxic/ischemic insult. Coexisting evidence of hypoxic/ischemic damage in posttraumatic cases is not an uncommon finding.20 It is thought to reflect respiratory or circulatory failure at the time of head injury, although disturbances of cerebral autoregulation may also play a role. On the other hand, significant brainstem damage is a rare finding in prolonged survival in a vegetative state, which explains the recovery of sleep-wake function and autonomic cardiorespiratory control in this state.
It appears that thalamic damage may play a critical role in the genesis of prolonged postcoma unresponsiveness, as cases with relatively little cortical damage are well described. Adams and associates20 published detailed studies of the pathological findings in both nontraumatic and traumatic cases and compared the latter group with 35 traumatic cases in which patients recovered to a state better than vegetative state before death. In summary, patients who remained in a vegetative state generally had more extensive DAI, thalamic damage, or both. Patients with lesser degrees of subcortical damage nearly always had extensive thalamic damage. Higher functioning patients rarely had both bilateral thalamic damage and extensive DAI, and if thalamic damage was present, it was considered to be of a lesser degree. Thus, extensive bilateral damage to the thalamus appears to be critical for the development of the vegetative state, especially if damage elsewhere is minimal.
DIAGNOSIS
Misdiagnoses of the vegetative state and the minimally conscious state appear to be common.23 Repeated clinical assessments are necessary to clearly establish whether reliable evidence of cognitive function is present in a severely brain-damaged patient. Patients are often in an intensive care environment when the diagnosis is first considered, and varying levels of potentially sedating medications may complicate the assessment. Similarly, metabolic manifestations of other major organ involvement may confound the clinical picture. Neurologists and intensive care physicians may disagree as to whether visual fixation or tracking is present or whether a particular movement is purposeful or reflexive. Nursing staff are often particularly helpful in determining whether an orienting or purposeful response can be consistently linked to a particular stimulus, especially if there is some fluctuation caused by extraneous factors such as seizures or bolus doses of anticonvulsants.
NEUROPHYSIOLOGICAL ASSESSMENT
Electroencephalography
Certain electroencephalographic patterns are known to be associated with extremely grave outcomes. Care must be taken to ensure that sedative medications, hypothermia, and severe metabolic disturbances are not confounding the interpretation of the record. In the setting of anoxic/ischemic cerebral injury, several electroencephalographic patterns have been associated with either a fatal outcome or, at best, survival with severe neurological sequelae.24 Of these patterns, the isoelectric or “flat” EEG after the first 24 hours is invariably associated with a poor outcome. The burst-suppression pattern (Fig. 9-1), especially if accompanied by generalized (typically facial and axial) myoclonic status25; the continuous bilateral periodic EEG or generalized epileptiform EEG (Fig. 9-2); and alpha (Fig. 9-3) and theta coma (Fig. 9-4) patterns usually but not invariably indicate a poor prognosis. Serial EEGs are sometimes necessary to identify a deteriorating trend.
