The Origins of the Vegetative State

Our story begins with the publication of the landmark Lancet paper describing the persistent vegetative state by Bryan Jennett and Fred Plum.^{Footnote 12} These were two giant figures in clinical neuroscience. Jennett was the Scottish neurosurgeon who promulgated the Glasgow Coma and Outcome Scales. Plum was the American neurologist who first identified the Locked-in-State and was the long-time chairman of neurology at Cornell, where he was my teacher. They came together in 1972 to describe a “syndrome in search of a name,” writing of a state of wakeful unresponsiveness in which the eyes are open, but there is no awareness of self, others or the environment, a function of isolated brain stem activity without higher cortical function.

It is interesting to note that the unresponsive wakefulness syndrome (UWS) which has come into vogue amongst European neurologists,^{Footnote 13} derives almost literally from the original description of the vegetative state by Jennett and Plum, but with a critical difference. In their paper, Jennett and Plum observe of the persistent vegetative state that, “it seems wakefulness without awareness.” (Italics added.) While this statement gives authorial provenance to Jennett and Plum for UWS, it also provides a nuanced view on their confidence in definitively asserting that the wakefulness of the vegetative is invariably without underlying awareness. Or put another way, what is observed at the bedside may not correlate with what might actually be going on inside the brain.

Plum was an exceedingly skilled editor and wordsmith. The insertion of “seems” was certainly not accidental but rather an intentional hedge against the possibility of observational error at the bedside producing a discordance with an internal brain state. This degree of semantic precision was exceedingly prescient in 1972, given that functional neuroimaging did not yet exist to query the injured brain and demonstrate such variance.

Jennett and Plum’s caution has been borne out by a history neither lived to see. We now appreciate that a staggering number of patients in chronic care who appear to be in the vegetative state following traumatic brain injury are actually in the minimally conscious state. We also have come to appreciate that patients who appear vegetative at the bedside can harbor covert consciousness and demonstrate volitional responsiveness when given neuroimaging tasks. Both of these groups of patients appear vegetative but are wakeful and responsive. But until they are identified, their covert consciousness is further obscured by labelling them as UWS.

Jennett and Plum understood the limits of the neurological phenotype to fully capture a patient’s actual brain state. Absent some deeper knowledge of brain circuitry or neurological genotype—to borrow a Mendelian analogy^{Footnote 14,Footnote 15} —one could only assert that patients who appeared vegetative seemed awake without awareness. Of course the use of the allegedly more “progressive” UWS designation for this brain state simply asserts unresponsive wakefulness without the critical admission that it might be misleading. While Jennett and Plum’s caution was brilliantly foresighted four decades ago, the invocation of UWS constitutes erroneous usage today when we know that there can be a discordance between one’s behavioral exam and inner state. Renaming the vegetative state as UWS makes the name less precise diagnostically.

The usage of UWS however was not motivated by diagnostic considerations. Instead, it was driven by a desire to counter the perception that the vegetative appellation was demeaning, given its apparent equation of those in that state with a vegetable. Regrettably, this new language has failed to take account of some old history.

In a 1998 essay Plum himself counters this pejorative linkage, explaining the origins of the vegetative state. He asks, “How did the vegetative state gets its name? Not as the reader might think. Patients’ families sometimes challenge us, implying that we have regarded the patient as a vegetable. Not so! The conception of a vegetative nervous system goes a long way back.”^{Footnote 16}

Recently, Zoe Adams and I have recounted the etymology of the vegetative appellation drawing on Plum’s scholarship.^{Footnote 17} Plum traces the origins of the vegetative state to the French physician Xavier Bichat (1771–1802), and the American neurologist and endocrinologist Walter Timme (1874–1956), who draws a line to Aristotle’s De Anima [On the Soul].^{Footnote 18,Footnote 19} To characterize the awake but unresponsive state, Plum invoked a bifurcated nervous system as articulated by Bichat who wrote of a vie de relation (animalic) versus vie de nutrition (vegetative) nervous system. Plum felt that invoking vegetative as a classification was preferable to other names in use at the time such as apallic syndrome or coma vigile.

Aristotle, himself a classifier and a botanist, introduces the vegetative faculty in Book II of De Anima. In his taxonomy the first faculty is nutritive or vegetative. It is foundational and modeled on the plant. In Aristotle’s formulation, the vegetative can neither sense nor perceive. Beyond the vegetative, there is sensation, movement and thought, the purview of animals and humans. These are ascending and dependent hierarchical faculties, much like Jennett and Plum conceived the relationship between the autonomic brain stem and the cerebral cortex. But unlike the synergism of the autonomic and higher integrative functions in Jennett and Plum’s formulation, Aristotle held that the vegetative and higher levels of function are binary and distinct. They do not interact as they do in the human brain. An entity, or being, is either one or the other in this dichotomous and static taxonomy. Human consciousness, in contrast, depends on both the brain stem and cortex. The former for arousal the later for integrative functions. If only arousal is present, the patient is wakeful but unresponsive, e.g., vegetative.

In formulating their definition, Jennett and Plum were also concerned about the duration of the vegetative state and how to characterize temporal issues. They chose persistent as the modifier and not permanent to convey the contingency of its duration. This left open the possibility of further recovery over time. They wrote:

Jennett and Plum’s hesitancy to conclude that the vegetative state was permanent, coupled with their insertion that the individual in that state seems to be unaware reflects their caution with respect to categorization and temporality. The redesignation of the permanent vegetative state as chronic speaks to the rigor of Jennett and Plum’s original formulation and the precision of their analysis.

Legacy of Quinlan

Despite these clinical caveats, in jurisprudence the Quinlan decision became all about irrevocability and the futility of the vegetative state. Drawing upon Dr. Plum’s testimony, who served as a court appointed expert, Chief Judge Hughes of the New Jersey Supreme Court delimited a right to die that was closely linked to the futility and irreversibility of the vegetative state. He wrote, … “It was indicated by Dr. Plum that the brain works in essentially two ways, the vegetative and the sapient…We have no hesitancy in deciding…that no external compelling interest of the State should compel Karen to endure the unendurable, only to vegetate a few more measurable months with no realistic possibility of returning to any semblance of cognitive or sapient life.”^{Footnote 21}

Here the moral warrant to withdraw life-sustaining care is the loss of higher cognitive function with no realistic possibility of its return. And yet, it is a curious decision. If the vegetative state was what it purported to be, then how could Ms. Quinlan “endure the unendurable”? It is unlikely that this aside was a misstatement about Ms. Quinlan’s inner state. Judge Hughes had just adjudicated that she had no realistic possibility of recovery based on Plum’s testimony. It is more likely that Judge Hughes’ opinion reflected the discomfort of those around Ms. Quinlan who found life without the return of cognition and sapience a life without meaning and untenable. Those losses, central to the return of personhood, were unendurable for her family and friends. Faced with this tragedy, the withdrawal of life-sustaining therapy became proportionate and indeed, preferable.

This set a precedent for our attitudes toward end-of-life care. Over the ensuing decades, physicians became acculturated to a right to die grounded in the ultimate futility of the vegetative state. It was a condition in which nothing can or should be done. These injuries were immutable, and thus interventions were disproportionate. And the data supported that view. Take the Quinlan autopsy results published in the New England Journal of Medicine in 1994.^{Footnote 22} Her brain was a gelatinous gel with a thin cortex and hydrocephalus ex vacuo. It weighed just 835 grams, just over half of a normal weight, after a decade of degeneration. This was not a biological substrate that could undergird consciousness.

The futility and permanence of the vegetative state became more deeply associated with the right to die. In an editorial accompanying the publication of the autopsy results, Marcia Angell of the New England Journal of Medicine explicitly made the link, thanking the Quinlans “for turning their personal calamity into a public benefit by launching the right-to-die movement.”^{Footnote 23} This association was continued in other cases involving young women in the vegetative state, notably the case of Nancy Beth Cruzan^{Footnote 24} and the national debate over Terri Schiavo.^{Footnote 25} The former was litigated in the US Supreme Court and the latter drew the attention of President George W. Bush and the US Congress.

The presumption was that these people were not going to get better, fostering therapeutic nihilism and a static view of brain injury. In clinical practice, this led to premature decisions to withhold or withdraw life-sustaining therapy, to donate organs, institute palliative care referrals, or discharge to nursing homes ill-equipped to care for patients still acutely recovering from their injuries.

To be clear, I am neither against palliative care nor questioning the right of patients or their surrogates to make choices at life’s end. I wrote a book on the topic and have been an advocate for improved palliative care for dying patients.^{Footnote 26} My point is that these questions need to be informed choices that reflect the possibilities for recovery and which are not engineered to a specific outcome, one way or another. That is, we need to both preserve the right to die and affirm the right to care for those who seek it.^{Footnote 27} Unfortunately, practice patterns have stressed the former at the expense of the later.

A paper from Neurology by Wijicks and Rubinstein entitled, “The family conference: End-of-life guidelines at work for comatose patients” is reflective of these attitudes. The authors provide their readers with the following guidance:

This is problematic on multiple scores. First, is time course. The title of the piece speaks to advice related to comatose patients. We know that coma is a self-limited state, generally lasting two weeks unless it is medically prolonged. These recommendations indicate that the prognosis will become clear this early during the course of care. Second, there is a presumption of futility, when it may not exist, and the paternalistic directive to convince families to lower their expectations and withhold or withdraw aggressive care that is proportionate to the patient’s condition. Of course, in many cases, the patient’s prognosis remains unknown while still in coma.^{Footnote 29}

A narrative from Rights Come to Mind provides a graphic illustration of the counsel offered by Wijicks and Rabinstein. The patient was a young Marine who was struck by a car as a pedestrian just before his deployment. In an IRB-approved study of family narratives of patients with disorders of consciousness done to research my book, she recounted the following exchange with her son’s neurologist:

Needless to say, this is a troubling account. The language is horrific. The allusion to a pithed frog from high school biology is a rather callous way to describe his brain state. And the time course is premature, so soon after the injury.

Beyond the anecdotal, there is epidemiological evidence that these attitudes have had an impact on outcomes. A study from Canada indicated the impact of decisions to withdraw life-sustaining therapy on hospital mortality in patients with traumatic brain injury. Overall in-hospital mortality was 31.7 percent with decisions to withdraw life-sustaining therapy, accounting for 70.2 percent of these deaths.^{Footnote 31}

How do we account for these practice patterns? I believe they are shaped by broader cultural perceptions dating to Quinlan, and flawed analogic reasoning. I do not think it stems from the mal-intent of physicians. Instead, I believe these practices originate in concluding that the loss of consciousness which characterizes severe brain injury is analogous to its loss in end-stage disease.^{Footnote 32} In most areas of clinical practice, the loss of consciousness represents the sequela of a terminal illness, end-stage dementia, advanced cancer, or renal disease. Surrogates take the patient’s loss of consciousness, and inability to interact, as a prompt to make decisions to withhold or withdraw life-sustaining therapy.

In contrast, TBI patients present with a loss of consciousness. That is where the process begins, not necessarily where it ends. While an initial loss of consciousness can be a terminal event, it can also be the pathway to recovery. To presume that the loss of consciousness in TBI is analogous to that in other areas of practice is to misconstrue its prognostic significance. This error, coupled with the presumption that the treatment of severe brain injury is invariably futile, leads to the high rates of withdrawals of life-sustaining therapies early in the course of care and the placement of many patients in what is euphemistically described as “custodial care,” where they are deprived of adequate rehabilitation.^{Footnote 33}

A Counter-Narrative

Although it was out of our gaze, there was a counter narrative to the presumptive futility of brain injury. In an undated manuscript from his archives housed at New York Weill Cornell Medicine from the 1970s, Plum sought to risk-stratify patients with severe brain injury who might be helped. He wrote that:

For Plum, the identification of the vegetative state was more than helping to advance a right to die, which he endorsed, but also the prompt to classify and distinguish brain states and prognosis. It was not just about the futility of care but its possible utility.

In 1977, just two years after Ms. Quinlan’s overdose, which placed her into the vegetative state, Plum was profiled in The New York Times, conducting a study, with Jennett in Glasgow, on outcomes from severe brain injury.^{Footnote 35} They tracked over 1,000 comatose patients treated in New York and Glasgow for at least two years to assess treatments, improve prognostication, and develop practice guidelines to help inform family choices. As Plum described it, the task was to articulate “the scientific basis of tomorrow’s medical ethics.”^{Footnote 36} Through these efforts, he was tightly linking ethics to empiricism, implicitly acknowledging that the right to die was not the only plausible option.^{Footnote 37}

By 1994, the state of knowledge had progressed to further refine the vegetative state into persistent and permanent subcategories. The Multi-Society Task Force (MSTF) determined that the vegetative state became persistent once it has persisted for one month and that it became permanent three months following anoxic injury and 12 months after traumatic brain injury.^{Footnote 38} But even here, there is more nuance than first appears. While the notion of permanence is often taken as self-fulfilling, the distinction is contingent and probabilistic. James L. Bernat, a distinguished neurologist and participant in the efforts that scripted the MSTF, spoke about the debate on the new nomenclature and its limits. He told me that:

In this frame, permanence becomes probabilistic. It is not a diagnosis but rather a prognosis about a future state. This language was prompted, in part, by the rare outlier cases who seemed to recover outside the aforementioned temporal markers for permanence.

By the late 1990s, it was becoming clear that nested within the vegetative cohort were minimally conscious (MCS) patients who did not behave like classic vegetative state patients.^{Footnote 40} They seemed to defy the definition of permanence, and demonstrated rare behaviors that betrayed the vegetative diagnosis. Unlike the wakeful unresponsiveness of the vegetative patient, MCS patients were responsive to the environment, albeit episodically and inconsistently. They might reach for a cup, say their names, or look up at someone who entered the room.

First described in 1997,^{Footnote 41} with the classification codified in 2002,^{Footnote 42} MCS patients were biologically distinct from vegetative ones. On functional neuroimaging MCS patients had widely distributed neural networks,^{Footnote 43} in contrast to vegetative patients who did not exhibit these network responses.^{Footnote 44} This was a key distinction with functional implications with respect to the processing of language and perception of sensory input, including pain.^{Footnote 45,Footnote 46}

Beyond demonstrating the differing neurophysiologic substrates of the vegetative and minimally conscious states, neuroimaging also revealed the limitations of behavioral assessment at the bedside. In 2006 Owen and colleagues demonstrated “awareness” in a patient who was clinically vegetative on examination. When asked to imagine herself playing tennis, walking about her house and disaggregating linguistically similar words, she lit up motor, spatial and language regions of interest on volitional imaging.^{Footnote 47}

This was a highly significant finding because it revealed covert consciousness. This was exactly what Jennett and Plum had so presciently anticipated back in 1972.^{Footnote 48} With the advent of modern neuroimaging, a patient who seems wakeful and unresponsive can be revealed as harboring covert consciousness. With my colleague, Nicholas D. Schiff, I described such patients as being in a nonbehavioral minimally conscious state, noting the discordance between what was observed and the underlying brain state of the patient.^{Footnote 49}

Schiff has since expanded this concept to a broader range of patients with cognitive motor dissociation (CMD).^{Footnote 50} CMD patients are unresponsive at the bedside but demonstrate volitional responses on fMRI. They can range from those in MCS up to those in the Locked-in-State. More recently, Edlow and colleagues have demonstrated covert consciousness in TBI patients while still in the intensive care unit.^{Footnote 51} Both of these findings have clinical and normative implications for patient assessment and care. They suggest the need for a new nosology that accounts for the possibility of covert consciousness in patients with both acute and chronic injury.^{Footnote 52}

Nosologic Humility and Neuroscience

As I reflect upon the normative importance of covert consciousness, I can not help but recall the story of Terry Wallace, an Arkansan man who sustained a severe head injury following a motor vehicle accident in 1984. For nearly two decades he was thought to have been in the vegetative state. That is, until 2003 when he began to speak spontaneously, demonstrating that he was minimally conscious. A subsequent review of his medical records suggested that he had been in the minimally conscious state for most of the time following his injury. His covert consciousness only became apparent when he began to speak.

But there is chilling evidence from 1993 that he was aware and yet unresponsive.^{Footnote 53} As told to me by his mother, Angilee, and recounted in Rights Come to Mind, Terry was residing in a nursing home. A roommate with advanced dementia got tangled up in his bedsheets and asphyxiated himself. Although it was clinically impossible for a vegetative patient to be upset by the tragedy, a nurse’s aide intuited that Terry was distressed and called his mother to come by. When Mrs. Wallis arrived, “Terry was lying there with his eyes open wide, he would not go to sleep, I mean he was making no noise at the time.” Only later, after he began to talk and was told that he had likely been minimally conscious at that time did Mrs. Wallis appreciate that Terry had been able to appreciate the night’s events. In retrospect, she realized, “So I don’t know what he saw, I know he saw something. And I know it had, now, I knew then it had to be something bad.”

Nosologically, there was not a name for Terry’s condition. He was diagnosed as being in the vegetative state but had covert consciousness. The minimally conscious state would not be codified for another decade. This should give us pause and harkens back to the original nosological humility of Jennett and Plum, when they cautioned that patients seem wakeful and unresponsive. Our descriptive nosology is still but a poor proxy for the circuit-based mechanisms that inform the patient’s functional status.

We are just beginning to appreciate the neurophysiologic dimensions of classification. At a structural level, functional neuroimaging has suggested dynamic white matter changes in his brain that might account for his recovery into the minimally conscious state.^{Footnote 54} Using diffusion tensor imaging, Voss et al. demonstrated axonal sprouting and pruning in Wallis’s brain, 19 years after his injury. These new white matter connections between remaining neurons may have been the biological basis for his recovery and ability to interact, decades after his injury. More recently, Thengone et al. reported similar longitudinal white matter changes in another subject, Maggie Worthen, who is profiled in Rights Come to Mind. Over a 54 month period, her brain demonstrated white matter changes across the hemispheres and in Broca’s area that correlated with an improved ability to communicate.^{Footnote 55}

These findings suggest that brain injuries are potentially dynamic and not static.^{Footnote 56} Remarkably, in the process of recovery, the brain is recapitulating a normal developmental process of sprouting and pruning in the service of brain repair. This suggests that the current time frame allocated to rehabilitation is inconsistent with the time course of biological recovery. It suggests that we should recast rehabilitation as education.^{Footnote 57,Footnote 58}

Moving from the biology of these brain states to their epidemiology, Terry’s experience also prompts a question: How many people are in nursing homes, like Wallis, unidentified with covert consciousness?^{Footnote 59} Schnakers et al. provide a sober response. She and her colleagues found that 41 percent of TBI patients in chronic care, thought to be vegetative, were in fact in the minimally conscious state when assessed behaviorally with the Coma Recovery Scale-Revised.^{Footnote 60} Often invisible, these patients have the potential to perceive and engage, even if they are ignored and assumed not to be there. One can only imagine the sense of isolation and loneliness that these patients experience.

Recovery, Resilience, and Rights

The great American pragmatist, John Dewey observed the power of science to transform categories and recast normative responsibilities. He wrote, “Inventions of new agencies and instruments create new ends. They created new consequence that stir men and woman to form new purposes.”^{Footnote 61} Neuroimaging and our deepening understanding of the circuitry of consciousness, notably the description of the meso-circuit,^{Footnote 62} have led to pharmacologic and device dependent interventions to harness the potentiality of the injured brain. Early progress has been made with: the advent of deep brain stimulation^{Footnote 63} and derivative approaches such as transcranial magnetic stimulation^{Footnote 64} and directed ultrasound;^{Footnote 65} as well as pharmaceutical interventions (Amantadine) that have accelerated^{Footnote 66} or (Zolpidem) that have prompted state changes^{Footnote 67} resulting in the recovery of consciousness. While much of this progress is in the proof-of-principle stage, the dawn of a therapeutic era for disorders of consciousness is fast approaching.

Now that we can appreciate that there is covert consciousness and have a means to identify it and intervene, we can not turn away. Writing the majority opinion in the Obergefell decision which decriminalized gay marriage, Justice Anthony Kennedy wrote that, “New insights and societal understanding can reveal unjustified inequality within fundamental institutional that once passed and unnoticed and unchallenged.”^{Footnote 68}

These patients suffer from a degree of inequality unseen elsewhere in society. They remain segregated in chronic care, far from the advances in neuroscience where their conditions could be better identified and ameliorated. It was to this health disparity that the AAN/ACRM/NIDDLR practice guideline spoke.^{Footnote 69} But the challenge is not just one of access to care.^{Footnote 70} Instead it is a question of rights, of fundamental equality, necessitated by new scientific insights, to borrow Justice Kennedy’s formulation.

As I have written elsewhere,^{Footnote 71,Footnote 72,Footnote 73,Footnote 74} the neglect and marginalization of patients with disorders of consciousness is a violation of the Americans with Disabilities Act,^{Footnote 75,Footnote 76} and the UN Convention on the Treatment of Persons with Disabilities.^{Footnote 77} To ignore their consciousness is a fundamental violation of their personhood.

History has been kind to the careful contingency of Jennett and Plum’s original formulation.^{Footnote 78} They were categorical neither about their certainty about the apparent wakefulness and unresponsiveness of the vegetative state nor its permanence. History will judge our generation too and ask how we perpetuated the fundamental injustice of treating conscious individuals as if they were not.