In 1972, Jennett and Plum named and described the persistent vegetative state (PVS), a syndrome, previously called apallic syndrome or coma vigile, marked by chronic unresponsiveness plus eyes-open wakefulness without awareness. Jennett and Plum sought to describe a syndrome that could be diagnosed behaviorally at the bedside and that would not imply any particular etiology or lesion. They fatefully adopted the term vegetative from archaic usage in the Oxford English Dictionary to “describe ‘an organic body capable of growth and development but devoid of sensation and thought (1764)’” and vegetate, meaning “to live a merely physical life, devoid of intellectual activity or social intercourse (1740)” [1]. The term “vegetative” had been used informally to describe comatose patients for a century. Jennett and Plum intended for the term to indicate to doctors a condition in which autonomic functions continue while “the cerebral cortex is not functioning,” and they sought terminology that laypersons could understand. Unfortunately, it quickly took on a more pejorative connotation, as patients were referred to as “vegetables,” implying that they were not fully human.

Jennett and Plum described PVS patients as hopeless cases, “incapable of communication and without hope of recovery as social human beings.” The “hopeful” cases, they said explicitly, are the ones who awaken from coma with signs of cortical functioning, unlike the PVS patients. In this description and designation of the PVS, the idea of hopelessness makes an early appearance, and Jennett and Plum were well aware of its ethical and social significance:

… the immediate issue is to recognize that there is a group of patients who never show evidence of a working mind… Certainly the indefinite survival of patients in this state presents a problem with humanitarian and socioeconomic implications which society as a whole will have to consider. If it were possible to predict soon after the brain damage had been sustained that, in the event of survival, the outcome would be a vegetative, mindless state, then the wisdom of continuing supportive measures could be discussed. [1]

Thus, early in the history of PVS, ethical questions were raised about whether life is worth living for these “mindless” patients, who were viewed as the unfortunate collateral damage of the effort to save the lives of patients with severe brain damage. Saving those who were not hopeless cases meant saving some who were, because outcomes could not be predicted.

That sense of hopelessness continues to be pervasive and persistent in both medical and bioethical discourses. PVS has been called “a fate worse than death” [2], in which maintaining life support is a “futile endeavor” that cannot benefit the patient [3]. PVS patients are frequently characterized as dead, as in this account that describes a doctor as “non-dead” and “lying in an open grave,” someone who suffers “the ultimate curse” [4]. It has been argued that the patient should be considered dead, because “the body in PVS has lost all forms of personhood” [5]. The humanity of vegetative patients has been challenged on the grounds that “they permanently lack the most essential feature of the human being, which is its undisputed capacity for living the life of a person, or rational self-consciousness” [6]. The perception that the vegetative state is a condition worse than death is widely endorsed by the public [7], with some attributing less mind to the vegetative patient than to the dead and viewing them as “more dead than dead” [7]. Many family members view their loved ones as being in an ambiguous state—not straightforwardly alive and not simply dead [7, 8].

A mere 3 years after the Jennett and Plum paper appeared, the Karen Ann Quinlan case emerged as a pivotal legal and bioethical case involving the right to die for PVS patients. In upholding the right of Quinlan’s parents to withdraw life support, the New Jersey Supreme Court noted that the state had no important interest in compelling Quinlan to “endure the unendurable, only to vegetate a few measurable months with no realistic possibility of returning to any semblance of cognitive or sapient life” [9]. The court considered her condition to be “debilitated and moribund” and “cruel and most unusual” [9]. Those views were echoed several years later by the United States Supreme Court in the Nancy Cruzan case: “If she has any awareness of her surroundings, her life must be a living hell” [10]. Justice Stevens argued for the propriety of considering quality of life in right to die cases:

It is appropriate to consider the quality of life in making decisions about the extraordinary medical treatment. Those who have made decisions about such matters without resort to the courts certainly consider the quality of life, and balance this against the unpleasant consequences to the patient. [10]

In the case of Tony Bland, the British High Court concluded that “To his parents and family he is ‘dead.’ His spirit has left him and all that remains is the shell of his body” [11]. That ruling prompted Jennett to grant the possibility of recovery from the PVS, which he noted would be more curse than blessing: “The recovery of a limited degree of awareness may indeed be worse than non-sentience for the patient.” Jennett praised the High Court for judging that it would be in Bland’s best interests to have artificial nutrition and hydration withdrawn, noting again that the price of saving those patients with a “reasonable probability of meaningful recovery and of regaining life as a social person” is paid by “patients who die after a fruitless fight in intensive care or survive with irreparable brain damage” [12].

The right to die debate and DoC have thus been entwined from the beginning, and it was the utter hopelessness of the PVS that inspired and gave fuel to those who fought for the legal right to die with dignity, without medical interventions maintaining a life some view to be pointless, perhaps even worse than death. Indeed, when Jennett and Plum wrote of the PVS [1], it was a seemingly hopeless condition, an artifact of medical progress that saved many lives, but did so indiscriminately, without the capacity to distinguish those who would go on to have “reasonable” recoveries and those who would remain forever trapped in a meaningless existence.

Twenty-two years after the PVS was named and defined, temporal criteria were established to distinguish the persistent vegetative state from the permanent vegetative state [13]. By then, it was understood that some patients do recover from a VS.¹ Unfortunately, the persistent and the permanent VS have the same initials, which continues to cause confusion among the public and popular press. The temporally, diagnostically, prognostically, and ethically distinct states continue to be conflated in the bioethics literature as well.

The diagnostic criteria for the minimally conscious state (MCS) were formally defined in 2002 [14]. The ethical significance of the MCS is difficult to overstate. First, because some patients progress from the VS to the MCS, its existence is proof that the VS is not always permanent, and not so certainly hopeless. Second, because the prospect of further recovery is better in the MCS, it shows that even severe brain injuries are not as hopeless as once thought. Finally, it is evidence of a significant problem of misdiagnosis—one that has resisted improvement for decades. The rate of misdiagnosis in DoC is estimated to be 39–43 % [15, 16], which would be unacceptably high in any area of medicine but is of special concern with DoC, where there is a type II or false-negative error: patients are diagnosed as unconscious when they are in fact conscious. The error occurs because the MCS can be exceedingly difficult to distinguish from the VS and because of a kind of self-fulfilling prophecy: when the VS is believed to be permanent, subtle signs of recovery are ignored or unnoticed. The diagnostic and prognostic error can prompt limitations or withdrawals of care for patients, on the belief that further care would be of no benefit. This creates a cycle of neglect, as patients who are believed to be permanently vegetative do not receive the care that might alter their prognosis or uncover signs of recovery.

In recent years, active neuroimaging paradigms using mental imagery tasks have revealed behaviorally unresponsive, covertly aware patients diagnosed in a VS who can willfully modulate their brain activity on command, indicating consciousness [17–19]. Given the problem of misdiagnosis in DoC, the ability to detect a misdiagnosis or effect a rediagnosis through neuroimaging would be tremendously valuable, especially for that subset of patients who regain consciousness undetected. Bedside behavioral diagnosis is susceptible to type II errors but so too neuroimaging. The essential problem, known to philosophers as the problem of other minds, is that the subjective consciousness of others cannot be directly observed. It can only be inferred from indirect evidence, such as behaviors. If neuroimaging provides indirect, objective, and reliable evidence of consciousness in the form of apparently willful brain behaviors [20], it does not provide similarly reliable evidence of unconsciousness. Thus, active neuroimaging paradigms are not immune to false negatives—they might also fail to detect consciousness in some conscious subjects. The “gold standard” for diagnosis of DoC, the bedside behavioral exam, cannot confirm consciousness in behaviorally unresponsive patients, so there is for now no way to completely eliminate false negatives or to disentangle whether the causes of negative neuroimaging findings are a failure of the imaging technique or a confounding factor such as aphasia or agnosia in an individual patient. Nonetheless, from the inference that some behaviorally unresponsive patients are conscious and capable of intentional brain behavior, there is a further inference to be made: there must be other patients whose consciousness remains undetected.

Misdiagnosis in patients who are behaviorally unresponsive, or minimally responsive, can take years or decades to discover. It takes on average 2.5 months to diagnose locked-in syndrome, which behaviorally mimics the VS although consciousness is intact; there are cases in the literature of diagnosis after 6 years, during which time the patient was thought to be unconscious [21]. Terry Wallis’ progression from VS to MCS remained undetected for almost two decades—until he began to speak—although his family long suspected that he was conscious [22]. There are many cases of unexpected recoveries in the literature, including patients who recover to states of partial disability, functional independence, and return to school or work, even after periods of altered consciousness lasting years [23–25]. Such cases raise questions about diagnostic accuracy, as well as the time-specific permanence of the VS.

In 2010, the European Taskforce proposed changing the name of the VS to unresponsive wakefulness syndrome (UWS), in part to end confusion about the permanent/persistent distinction and in part to ease the stigma attached to the term vegetative, which popularly implies a less-than-human status [26]. The new name would also describe the syndrome’s defining features—unresponsiveness and wakefulness—without implying that the patient is unconscious. This is a significant and controversial departure from the Jennett and Plum nomenclature. It grants the inherent uncertainty of unconsciousness, where previously there was implied certainty. UWS also abandons the certainty of permanence in light of the rare cases of late recovery from VS/UWS.

The erosion of diagnostic and prognostic certainty about DoC generates ethical uncertainties. Prognostication is ethically disquieting when it leads to self-fulfilling prophecies that in turn influence future prognostications. Physicians tend to overestimate poor outcomes and underestimate good outcomes, particularly when making early predictions [27–29]. Withdrawal of life-sustaining treatment (LST) is the leading factor in neurocritical intensive care unit deaths and precedes up to 70 % of neuro-ICU deaths [30–33]. When a high proportion of deaths follow from decisions to limit or withdraw LST, self-fulfilling prophecies create an epistemic challenge to prognostication: is there high mortality in the population of patients with severe brain injuries, or is high mortality caused by predictions of high mortality and morbidity that prompt the withdrawal of care? When predictions of mortality after brain injury are overestimated because of withdrawals of care, a false sense of hopelessness can result.

Given attitudes about the intrinsic badness of VS/UWS, there is a dilemma about what would be the worst possible outcome: life with severe disability or death when life could have been acceptable. This dilemma generates belief in a “window of opportunity,” a period of uncertainty soon after acute brain injury, when withdrawal of LST is very likely to lead to death, but when prognosis for survival or recovery with continued care is uncertain [34]. The window of opportunity creates a sense of urgency regarding withdrawal decisions, with the perceived risk being that the patient might recover sufficiently to be independent of LST—thus closing the window—but will survive with severe disability that might not be acceptable to the patient. Waiting for more prognostic certainty risks the closing of the window, and the resulting time pressure is costly, because avoiding the worst outcome for the patient—survival when death would be preferable—requires forgoing any possibility of an acceptable outcome [35]. The short window of opportunity forces early prognostication, which commingles with value judgments concerning acceptable outcomes. Death is a well-defined endpoint, but “poor functional outcomes” are more subjectively evaluative [36]. The prospect of a VS/UWS as one of the “poor functional outcomes”—it is one tick above death on the Glasgow Outcome Scale—certainly factors into decisions to withdraw LST [36]. Pressure to act before the window closes comes not from the possibility of an avoidable death but rather the chance that an opportunity to die will be missed [37], resulting in an avoidable survival in a condition worse than death. Yet, even if we accept the hopelessness of the permanent VS, many decisions to withdraw treatment occur within the first 72 h following injury [32], months before a diagnosis of permanent VS—and hopelessness—can be made. Here the words of Jennett and Plum prove prophetic: if it could be predicted soon after a brain injury that “the outcome would be a vegetative, mindless state, then the wisdom of continuing supportive measures could be discussed” [1]. Given the prevalence of withdrawal of care following severe brain injury, false hope appears not to be a problem, but perhaps false hopelessness is.