Disorders of Consciousness
Managing patients with disorders of consciousness presents challenging ethical issues for neurologists and neurosurgeons and raises vexing questions. How can physicians be certain that the patient is unconscious and unable to experience pain and suffering? How confidently can physicians prognosticate the probability and quality of the patient’s recovery? What duration of aggressive treatment is necessary before physicians can predict outcome with reasonable certainty? What is the appropriate level of treatment for the patient at each stage of illness? How should physicians counsel family members? Who makes treatment decisions for the incapacitated patient and by what criteria? How do physicians resolve conflicts among family members over medical treatment?
Disorders of consciousness comprise a continuum of severity from the deepest coma to the mildest confusional state and a spectrum of prognosis from the reversible to the permanent. Most physicians aggressively treat patients with coma hoping for improvement (excluding those who are brain dead), at least until their prognosis becomes clear. Irrespective of its cause, true eyes-closed coma usually is a temporary state lasting from between a few hours to a few weeks. Thereafter, most comatose patients achieve one of three outcomes: they die, they enter a vegetative state (VS), or they recover consciousness to a varying degree from a minimally conscious state (MCS) to normality.1 The VS and MCS may be transient stages during recovery after an acute brain injury or illness or may be chronic stable states that persist for months or years without improvement. Patients remaining in chronic VS and MCS account for the most difficult ethical issues encountered in the treatment of unconscious patients.
THE VEGETATIVE STATE AND THE MINIMALLY CONSCIOUS STATE
The vegetative state (VS) is a disorder of consciousness that ironically combines wakefulness and lack of awareness. When it occurs as a chronic stable disorder, it is commonly called the “persistent vegetative state” (PVS). Patients reach a VS after suffering a pathological process that has produced widespread dysfunction of cerebral cortical neurons, thalamic neurons, or the white matter connections between the cortex and thalamus, but that largely spares brain stem and hypothalamic neurons. The most common causes of VS are head trauma, stroke, and neuronal hypoxia and ischemia suffered during cardiopulmonary arrest.2
The VS is an artifact of modern technology because, formerly, most patients with brain injuries sufficient to cause this disorder would have died. Technologically advanced methods of restoring such patients to relatively normal health through cardiopulmonary resuscitation and other treatment often succeed. When these attempts fail to restore normal neurological function, surviving patients may be left in VS, a condition that some physicians have termed “a state worse than death.”3 The tragedy and meaninglessness of a chronically
non-cognitive existence create difficult ethical problems in the management of VS patients. In the United States in March 2005, many of these problems were brought to intense public scrutiny during the sensationalized dying of Theresa Schiavo.
non-cognitive existence create difficult ethical problems in the management of VS patients. In the United States in March 2005, many of these problems were brought to intense public scrutiny during the sensationalized dying of Theresa Schiavo.
History
In 1972, Bryan Jennett and Fred Plum coined the name “persistent vegetative state” and defined its essential clinical features, although others earlier had recognized and provided brief descriptions of similar states.4 Jennett and Plum observed that many patients rendered comatose from head trauma and other brain injuries progressed after several weeks from a typical eyes-closed, comatose state to an eyes-open unresponsive and unaware state. Although sleep-wake cycles returned and they were awake, these patients appeared to be utterly unaware of themselves and their environment. To the fullest extent that could be determined, they were incapable of thinking, remembering, feeling, or experiencing. With adequate medical and nursing care, young patients could remain in this state for many months or years.
Jennett and Plum chose the term “vegetative” to capture the essential characteristic of these patients. As they pointed out, vegetative is defined in the Oxford English Dictionary as “a merely physical life, devoid of intellectual activity or social intercourse … an organic body capable of growth and development but devoid of sensation and thought.” In retrospect, the term “vegetative” was an unfortunate choice because of its unintended similarity to the pejorative term “vegetable,” a term sometimes callously applied to non-cognitive patients. Jennett and Plum chose the adjective “persistent” to indicate that these patients had remained in this noncognitive state for a long time. The authors purposely avoided the term “permanent,” connoting a definite prognosis, because they recognized that often it is impossible to make such a prognosis with a high degree of certainty. Subsequently, other commentators have tried to equate the term “persistent” with the term “permanent” but, because some VS patients ultimately recover awareness, persistence is not synonymous with permanence. Stated another way, persistent vegetative state denotes a diagnosis whereas permanent vegetative state denotes a prognosis.
Over the past few decades, a number of case reports, a small series of patients, and several reviews have highlighted the clinical features and natural history of VS.5 Further, VS has been the subject of much writing in clinical ethics6 and the focus of several landmark high court rulings in the United States involving termination of life-sustaining treatment, most notably the cases of Karen Ann Quinlan, Paul Brophy, Nancy Beth Cruzan, and Theresa Schiavo.7 Despite the quantity of such writings, nagging areas persist in which lack of consensus has confounded discussion, especially surrounding the diagnostic criteria and prognosis of the VS.
In an attempt to address the medical and ethical problems in the management of VS patients, several medical societies have formulated diagnostic criteria and propounded prognostic assessments for VS.8 Although these efforts have been welcomed, they have not been accepted universally. Critics point out that statements of medical societies are learned assertions that do not necessarily result from an evidence-based review of the scientific literature.
The Multi-Society Task Force on PVS was impaneled in 1991 to try to achieve an evidence-based consensus on the medical aspects of VS. The Task Force was composed of experts representing the American Academy of Neurology, the American Neurological Association, the American Association of Neurological Surgeons, the American Academy of Pediatrics, and the Child Neurology Society. In formulating their report, the Task Force members reviewed the world literature on VS and studied relevant databases such as the National Institute of Neurological Disorders and Stroke Traumatic Coma Data Bank. Drafts of the report were circulated widely among other experts in the field of consciousness disorders to assure that the Task Force findings and conclusions represented the mainstream of current thought. The 1994 Task Force report was the most authoritative summary of medical facts on VS at that time.9 In the
United Kingdom, the Royal College of Physicians Working Group [on “Permanent Vegetative State”] published their findings in 1996 with a clarification in 2003 that reached many of the same conclusions as the Task Force.10
United Kingdom, the Royal College of Physicians Working Group [on “Permanent Vegetative State”] published their findings in 1996 with a clarification in 2003 that reached many of the same conclusions as the Task Force.10
Although the Task Force report generally was regarded as authoritative,11 it was criticized in some circles for failing to include representatives from rehabilitation medicine (who provide care for most VS patients), for overstating the confidence with which it asserted that VS patients were noncognitive,12 and for using circular reasoning about awareness in the definition of VS.13 The Quality Standards Subcommittee of the American Academy of Neurology subsequently derived practice parameters for the management of patients in VS from the Task Force report.14 The American Academy of Neurology is revisiting the subject of VS and is expected to publish an updated report in 2008 or 2009.
The terminology of the vegetative state has been plagued with confusion since it was coined. The modifiers “persistent” and “permanent” cause ambiguity. I agree with Bryan Jennett that it is best to use the term “VS” as a diagnosis without a preceding modifier such as “persistent” or “permanent.”15 The prognosis for a VS patient’s recovery of awareness is a critically important issue but it should be addressed separately, not by incorporating it into the name of the syndrome. In this chapter, I use “VS” to describe the syndrome and “PVS” only when necessary for historical accuracy.
Definition, Criteria, and Clinical Features of the Vegetative State
The Multi-Society Task Force on PVS operationally defined the VS as “a condition of complete unawareness of the self and the environment accompanied by sleep-wake cycles with either complete or partial preservation of brain stem and hypothalamic autonomic functions.” A VS may be a transient stage in the recovery from a diffuse brain insult or may be a chronic condition. The Task Force followed the 1972 usage of Jennett and Plum by defining PVS as a VS lasting longer than one month.16
The Task Force developed clinical diagnostic criteria for VS as listed in Table 12-1. The possible behavioral repertoire of VS patients is listed in Table 12-2. Patients in VS thus demonstrate intact sleep-wake cycles and can blink, move their eyes, swallow, vocalize sounds, breathe, grimace, and move their limbs. They may exhibit unsustained visual pursuit for a few seconds as well. Stereotyped movements resulting from intact subcortical motor reflexes may be present. Despite their repertoire of motor activities, VS patients execute none in response to command nor do they execute movements in a purposeful way that would suggest the presence of an aware, experiencing, responsive intellect.17
TABLE 12-1 Criteria for Diagnosing the Vegetative State | ||||||||||||||||||||
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TABLE 12-2 Potential Behavioral Repertoire of Patients in a Vegetative State | ||||||||||||||||||||||||||||||||
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The intact subcortical motor functions, brain stem reflexes, breathing, and generally preserved autonomic functions in VS patients result because brain stem and hypothalamic neurons are largely spared by the pathological process that destroyed or disconnected cerebral cortical and thalamic neurons. The VS patient retains wakefulness and alertness because the ascending reticular activating system of the brain stem is spared. Because the cerebral cortex or thalami are diffusely damaged or disconnected, awareness of self and environment is abolished and all cognition is absent despite wakefulness.
Patients in VS commonly are classified as unconscious, but the use of the term “consciousness” in this context is ambiguous. In their famous monograph, Fred Plum and Jerome Posner pointed out that normal consciousness has two necessary components: (1) wakefulness or alertness, served by the ascending reticular activating system of the brain stem and its thalamic and hemispheric projections; and (2) awareness of self and environment served by the cerebral cortex and its connections with itself, the thalami, and other subcortical structures.18
Patients in a typical eyes-closed coma are classified as unconscious because they lack both the wakefulness and awareness components of consciousness. Patients in VS possess wakefulness but lack awareness; thus they possess only one component of consciousness. Because both components are necessary for normal consciousness, and the absence of awareness is the most relevant characteristic of unconsciousness,19 VS patients reasonably may be classified as unconscious. That the VS patient possesses a relatively intact alerting mechanism is of no functional value in the absence of the capacity for awareness and cognitive experience.
The VS is distinct from other states of unconsciousness or severe paralysis. Brain death (chapter 11) requires the irreversible loss of all clinical functions of the brain, including those of the hypothalamus and brain stem. Coma is a pathological state of eyes-closed unconsciousness without sleep-wake cycles, which results from impairment of the ascending reticular activating system in the brain stem. The apallic syndrome is a particularly severe form of PVS.20 Akinetic mutism is a state of severe abulia with preserved awareness following bilateral orbitofrontal or bilateral cingulate gyrus lesions.21 The locked-in syndrome (chapter 14) is a state of pseudocoma featuring profound paralysis but preserved awareness; it usually caused by an acute, large lesion of the pons, usually of vascular origin, though similar states of profound paralysis with intact awareness can result from advanced states of neuromuscular diseases. In a clever turn of phrase, Hannah Kinney and Martin Samuels called the VS a “locked out” syndrome because the cerebral cortex is disconnected from the external world, in contrast to the “locked in” syndrome in which the patient has preserved awareness but profound paralysis.22 Because the criteria of VS have become accepted it is desirable to abandon using the overlapping terms apallic syndrome and akinetic mutism.
Definition, Criteria, and Clinical Features of the Minimally Conscious State
Just as patients evolve from coma to VS several weeks following a diffuse brain insult, some patients may recover from VS weeks or months later to enter a state of unresponsiveness in which awareness is present, at least to some extent, and at some times. This state recently has been called the minimally conscious state (MCS).
Although patients in this condition have been described for years, classifying them as MCS, primarily by experts in traumatic brain injury rehabilitation, is a product only of the past decade.23 The Aspen Neurobehavioral
Conference impaneled a task force to study the available literature and seek consensus-based recommendations regarding the diagnosis, prognosis, and management of MCS. The report of the Aspen Neurobehavioral Conference defines the MCS as “a condition of severely altered consciousness in which minimal but definite behavioral evidence of self or environmental awareness is demonstrated.” They require that patients in MCS show “limited but clearly discernable self or environmental awareness on a reproducible or sustained basis” by demonstrating one or more behaviors, including following simple commands, gesturing yes/no answers to questions, intelligible verbalizations, purposeful behavior, appropriate smiling or crying, reaching for and touching objects, and pursuit eye movements.24 The criteria for MCS are listed in Table 12-3 and the potential behavioral repertoire of a patient with MCS is listed in Table 12-4. The differential characteristics of VS, MCS, coma, brain death, and locked-in syndrome are displayed in Table 12-5.
Conference impaneled a task force to study the available literature and seek consensus-based recommendations regarding the diagnosis, prognosis, and management of MCS. The report of the Aspen Neurobehavioral Conference defines the MCS as “a condition of severely altered consciousness in which minimal but definite behavioral evidence of self or environmental awareness is demonstrated.” They require that patients in MCS show “limited but clearly discernable self or environmental awareness on a reproducible or sustained basis” by demonstrating one or more behaviors, including following simple commands, gesturing yes/no answers to questions, intelligible verbalizations, purposeful behavior, appropriate smiling or crying, reaching for and touching objects, and pursuit eye movements.24 The criteria for MCS are listed in Table 12-3 and the potential behavioral repertoire of a patient with MCS is listed in Table 12-4. The differential characteristics of VS, MCS, coma, brain death, and locked-in syndrome are displayed in Table 12-5.
Like the VS, the MCS may occur as a transient stage in the recovery after severe head injury or other brain insult, or it may be a chronic, stable condition. With continued recovery, some patients emerge from MCS to a higher state of awareness. Evidence for this improvement is present if the patient can engage in functional interactive communication or use two different objects functionally. It is essential for clinicians to distinguish VS from MCS.
TABLE 12-3 Criteria for Diagnosing the Minimally Conscious State | ||||||||||||||
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TABLE 12-4 Potential Behavioral Repertoire of Patients in a Minimally Conscious State | ||||||||||||||||||
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Critics of the term “MCS” point out that the mere fact that these patients were poorly responsive did not necessarily imply that their consciousness was deficient. I believe that the term “minimally responsive state” more accurately describes their behavior.25 This term was used for these patients in the neuro-rehabilitation literature before “MCS” was coined.26 It is unclear why the more descriptive term “minimally responsive state” was abandoned in favor of “MCS.” Other critics worry that the category called MCS was created from within the continuum of brain-injured patients to accelerate the devaluation of their lives and to permit a more casual decision to discontinue their treatment.27
Patients with impaired consciousness, in whom the diagnosis of VS or MCS is being considered, need to be examined carefully and systematically to assess their level of awareness. Several clinical assessment scales that target responses of conscious awareness have been developed, tested, and validated in brain-injured patients.28 Physicians should examine patients in a distraction-free environment after tapering sedative medications to maximize the patients’ alertness.29 Commands to follow tasks should attempt to elicit responses that lie within patients’ capacities. Visual, auditory, tactile, noxious, and olfactory stimuli should be administered. Raising patients upright to 85 degrees on a tilt table can improve their responsiveness.30 Nurses and caregivers should be interviewed to determine if they have witnessed patient behaviors suggesting awareness. If so, they should be asked to elicit them for the examiner.
TABLE 12-5 A Comparison of Vegetative State, Minimally Conscious State, and Related Disorders* | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Limits of Diagnostic Certainty: The Role of Functional Neuroimaging Studies
By definition, VS patients are unaware. But how can physicians be certain that they are utterly unaware and incapable of thinking, suffering, or having any cognitive experience? Is it possible that VS patients are aware but we simply lack the means to detect evidence of their cognitive life and thus erroneously deny its presence?31 Do the motor responses of VS patients to noxious stimuli, such as limb withdrawal or facial grimace, indicate that they can consciously perceive pain and thus suffer?32 Of course, if the patient is found to be aware, the correct diagnosis must change from VS to MCS.
There is a fundamental and irreducible biological limitation in knowing for certain whether any other person possesses a conscious life. No person can directly experience the consciousness of another. We can ascertain another person’s quality and quantity of consciousness solely by inference. We interact with others and infer in them a particular level of conscious life on the grounds of their behavior and, in particular, the quality and quantity of their responses to our stimuli. If patients’ responses to our stimuli are markedly deficient or absent, we may reasonably infer a reduction in the quality and quantity of their consciousness.
Thus, it remains possible that VS patients are actually aware, and neurologists erroneously make an incorrect diagnosis by asserting that their awareness and cognitive life is absent when it is actually present.33 This type of diagnostic error has been made in the past, most commonly by the careless examiner of a patient with locked-in syndrome who, because of lack of response and pinpoint pupils, is erroneously labeled as unconscious (see chapter 14). Two studies of patients diagnosed as VS who then were carefully examined by experienced clinicians showed that 37% and 43% of the patients actually were aware and therefore in a MCS, not in a VS.34 It is probable these patients initially were in a VS but that they had improved over time to MCS and evidence for their awareness was not detected until they were re-examined.
Family members commonly assert that VS patients respond to them even when physicians cannot detect evidence of it.35 It is essential for neurologists to carefully examine patients with impaired responsiveness searching for any evidence of awareness. Routinely, I ask family members or nurses who have detected awareness behaviors to demonstrate them to me. Only if awareness is unequivocally absent should physicians diagnose VS.
In the previous edition of this book, I concluded that, despite an irreducible limitation of proof, we could justifiably conclude that properly diagnosed VS patients were incapable of any conscious experience, including the experience of pain or suffering. Now, in light of several recent provocative functional neuroimaging reports discussed below, I am no longer so certain. Previously, I cited three lines of empirical evidence that VS patients were unaware.36 First, the motor responses exhibited by VS patients to verbal, visual, auditory, somasthetic, or noxious stimuli achieve a level of complexity no greater than primitive involuntary subcortical reflexes seen in unequivocally comatose patients. VS patients respond to verbal and auditory stimuli by opening or randomly moving their eyes. They follow no commands. Their eyes and head can follow a visual stimulus briefly, but they show no signs of purpose, attention, planning, recognition, or sustained optical tracking or visual fixation. In response to noxious or other somatosensory stimuli, they assume stereotyped motor postures and have increased autonomic activity. The repertoire of VS patients’ motor responses to stimuli, thus, while not
excluding the presence of cognitive life, shows no convincing evidence of it.
excluding the presence of cognitive life, shows no convincing evidence of it.
Second, pathological studies of VS reveal diffuse cortical laminar or pseudolaminar necrosis or widespread bilateral thalamic necrosis in the majority of nontraumatic cases of VS and diffuse axonal injury in those cases in which VS was caused by head trauma.37 Based on our understanding of the anatomical structures necessary for awareness, we would expect the extent and severity of these lesions to produce a disorder so profound that VS patients could not retain any degree of awareness.38 There is obvious circularity in this reasoning, however, because our knowledge of the anatomy of consciousness is based on clinical-anatomic correlation.
Third, early functional neuroimaging studies revealed that VS patients had markedly diminished resting rates of cortical glucose consumption suggesting severe diffuse impairment of cortical function. Regional cerebral metabolic rates of glucose consumption (rCMRglc) measured by positron emission tomography (PET) scanning, a reliable indicator of cerebral cortical metabolism, are depressed to levels less than one-half normal values, a range seen in comatose patients and in normal individuals in the deepest planes of general anesthesia.39 The cerebral cortical functioning in VS patients thus is similar to that of normal patients in deep general anesthesia, who, as everyone agrees, are insensate and utterly incapable of experience.
More recent functional neuroimaging studies using PET and functional MRI (fMRI) to assess cortical responses to stimulation have further clarified the physiology of consciousness. That resting cerebral neuronal metabolism is abnormally depressed in VS patients does not necessarily mean that it might not be appropriately increased in response to stimulation. In a study of auditory processing in VS, Steven Laureys and colleagues used PET scanning to test for increases in regional cerebral blood flow and cerebral metabolism in response to auditory stimulation. They found that auditory click stimuli activated auditory cortex bilaterally but did not activate the contralateral auditory association cortex, the posterior parietal association area, the anterior cingulate cortex, or the hippocampus of patients in VS. They concluded that the activation of auditory cortices in isolation, without the multimodal and limbic areas, could not lead to the integrative processes believed to be necessary for awareness.40 In a subsequent study, they showed evidence for the return of normal thalamocortical conductivity after recovery from VS.41
Reviews of over a decade of functional neuroimaging studies in VS with PET and fMRI by Steven Laureys and colleagues and by Nicholas Schiff and colleagues have reached common conclusions.42 In VS patients, auditory, visual, and somatosensory stimuli can activate primary sensory areas but generally fail to activate secondary cortical areas and distributed cortical networks believed to be necessary for awareness. The absence of activation of higher order multimodal association cortices that provide the brain’s integrated, distributed neuronal networks is evidence that VS patients lack awareness.
Functional neuroimaging studies in MCS patients show very different results. Cortical activation to spoken voice studies in MCS patients show generally intact distributed language networks.43 In my recent review of these studies, I concluded “These preliminary functional imaging data suggest that some MCS patients retain sufficient cortical connectivity to support cognitive and linguistic processes, and may not be as ‘minimally conscious’ as their impaired responsiveness suggests.”44
Two recent provocative functional neuroimaging reports raise fascinating and disturbing questions about the sensitivity of the neurological examination to detect awareness. Adrian Owen and colleagues studied a 23-year-old woman in VS five months after a traumatic brain injury. When she was told to imagine playing tennis and think about the ball being hit back and forth across the net, her supplementary motor area was activated. When she was asked to imagine visiting each room in her house, activity was recorded in her parahippocampal gyrus, posterior parietal lobe, and lateral premotor cortex. Both findings were similar to the cortical activations recorded in normal controls with the same stimuli. The investigators concluded that “beyond any
doubt [the patient] was consciously aware of herself and her surroundings.” Six months later, she began to show clinical evidence of awareness.45 In retrospect, given this evidence that she was aware, it is reasonable to conclude that she was in a MCS despite her clinical diagnosis of VS made by competent examiners.
doubt [the patient] was consciously aware of herself and her surroundings.” Six months later, she began to show clinical evidence of awareness.45 In retrospect, given this evidence that she was aware, it is reasonable to conclude that she was in a MCS despite her clinical diagnosis of VS made by competent examiners.
H.B. Di and colleagues reported two patients clinically diagnosed as VS who showed cortical activation of perisylvian language cortex, similar to findings recorded in MCS patients, evoked by hearing their names spoken by a familiar voice. The small subgroup of VS patients who showed evoked cortical activation later developed clinical evidence for awareness whereas the larger subgroup of VS patients showing no activation did not.46 In an accompanying editorial, David Rottenberg and I opined that, although it is difficult to draw important conclusions from a few isolated reports, these cases suggested that the neurological examination, at times, may be insensitive to determine awareness. We predicted that once fMRI stimulation techniques become standardized and validated as a result of carefully studying many more patients, they will become an important ancillary test to the neurological examination in determining the diagnosis and prognosis of patients with VS and MCS.47
Pathogenesis, Pathology, and Epidemiology
Patients may reach a VS or MCS following diffuse brain injury or illness. The most common and poignant cases are young, previously healthy patients who have suffered massive head trauma. The second most common etiology is a nontraumatic event such as hypoxic-ischemic neuronal damage resulting from cardiopulmonary arrest. Infants born with anencephaly are in VS but poorly responsive infants born with hydranencephaly or other severe congenital malformations typically show fragments of awareness behavior and thus usually are in MCS.48
Formerly, VS was believed to be the common endpoint of chronic neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Creutzfeldt-Jakob, or Huntington’s disease.49 Although most experienced neurologists have seen cases of neurodegenerative diseases so far advanced that the patient was unresponsive, a study examining the frequency of such instances found that cases of true VS are rare. Ladislav Volicer and colleagues carefully examined 88 patients with the most advanced Alzheimer’s disease in an Alzheimer’s chronic care facility. Of three independent examiners, two diagnosed VS in two patients and one examiner diagnosed VS in five patients. The examinations were repeated two months later after they had better standardized their examination procedures. In the second examination, VS was diagnosed by one examiner in six patients and not at all by the other two.50 Thus, MCS is a more common diagnosis than VS in patients with endstage neurodegenerative diseases.
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