Differences That Make a Difference in Disorders of Consciousness

FROM FIXATION TO FLUIDITY

We are grateful to Fischer and Truog (2017) for their thoughtful commentary on our work on the minimally conscious state (MCS), disorders of consciousness, and the rights owed to this patient population. They have provided a serious and scholarly critique, and we are grateful for this opportunity to respond.

Our reply can be framed around two ironies embedded in their title: “the problem with fixating on consciousness in disorders of consciousness.” On the one hand there is an apparent contradiction in terms of wanting to remove the distinguishing aspects of consciousness from a suite of conditions marked by its profound alteration. On the other, there is a less obvious but perhaps more telling problem originating with the use of the verb, “fixating.”

This verb underlies their critique of our concern about the salience of consciousness, but its use also reflects the failure to consider the evolving nature of these conditions, which are not fixed but dynamic. Their approach to disorders of consciousness is atemporal and thus overlooks the critical clinical fluidity of the majority of these conditions, including the vegetative state (VS), at least over time periods in which appropriate allocations of resources remain inadequate. Ironically, by fixating on the metaphysical challenge of knowing the presence or absence of consciousness within a point in time where evidence may be ambiguous, the argument neglects how prognosis should inform the care of patients with disorders of consciousness and our normative obligations to them (Fins 2015).

Their point of view, however, is understandable and common. There is a tendency to think of the vegetative state¹ and minimally conscious state (Giacino et al. 2002) as if they were diagnoses when in fact they are states. States are not fixed, like a diagnosis, but rather conditions that can evolve and change over time (Fins 2008a). For example, the vegetative state can evolve into the minimally conscious state before it becomes chronic, generally understood to be 3 months after anoxic and 12 months after traumatic injury (Multi-Society Task Force on PVS 1994), although such framing is giving way to more biologically based assessments that recognize the limitations of behavioral assessments for even accurately sorting the variance within behavioral examination consistent within the vegetative state (Schiff 2015). For MCS, many notable exceptions exist, where patients erroneously thought vegetative actually remained in MCS and sustained very late recoveries. The best known example is the case of Terry Wallis, who began to speak after 19 years (Fins 2015; Schiff and Fins 2003). A number of papers have indicated that the error rate of misdiagnosing MCS as VS is upward of 40% (Schnakers et al. 2009; Andrews et al. 1996; Childs, Mercer and Childs 1993; Wilson et al. 2002).

The fluidity of these brain states is significant. After simply reaching the behavioral level of MCS, recovery to higher levels of function may be open-ended, as Lammi and colleagues and many other studies have now noted (Lammi et al. 2005). Thus, even chronic MCS denotes a state of potentiality not evident in patients in prolonged vegetative states. (Fins 2015). It is important to note that while patients at the lower end of MCS may not be meaningfully distinct from VS patients at a functional level, their prognoses remain a difference that is important and relevant for future potential recovery. Further confounding the overall picture is the increasing likelihood of hidden integrative cerebral capacities with worsening motoric function; as a result, some patients diagnosed as VS or MCS with low-level examinations may harbor cognitive capacities closer to the locked-in state and may be widely miscategorized without biologically based measures that are slowly coming into focus (Schiff 2015).

BIOLOGICAL DISTINCTIONS

This potentiality has its basis in a biological difference between the vegetative and minimally conscious state when accurately diagnosed, again pointing to why this distinction is critical to our thinking. Unlike the chronic vegetative state, chronic MCS can be an incubator for dynamic structural changes in the brain years after injury. Voss and colleagues (2006) first described very late structural alterations in the brain utilizing diffusion tensor imaging (DTI) of the aforementioned Terry Wallis (Fins 2015; Schiff and Fins 2003), a patient who remained in MCS for more than 19 years. The investigators proposed that axonal sprouting—new connections between remaining neurons—may have accounted for his return of speech nearly two decades after his injury.

Extending these observations, Thengone and colleagues (2016) prospectively tracked structural and functional changes in the brain of Maggie Worthen, a young woman whose story was told in Rights Come to Mind (Fins 2015). Over a multiyear period the region for expressive speech, Broca's area, showed marked structural and functional changes in Maggie's brain, including similar DTI changes emanating from Broca's area within the left hemisphere and across the hemispheres. These changes occurred in a graded fashion over a nearly 3-year period and correlated with her recovery of a narrow communication channel utilizing the left eye (Fins 2015, 2017a; Thengone et al. 2016).

Appreciating the neurobiological differences between the vegetative and minimally conscious states is rapidly becoming the basis for improved discrimination between these conditions, notwithstanding Fischer and Troug's contentions to the contrary, with many studies existing that support this emerging science. A full review of disorders is beyond the scope of this essay, and we refer the reader to a review article in Nature Reviews Neuroscience that we co-authored (Giacino et al. 2014), but simply put, the difference between the vegetative and minimally conscious states is one of functional integration.

The vegetative brain is dis-integrated and unable to work as a coherent unit (whether as a result of a reversible functional alteration or permanent loss of functional connectivity) (Laureys et al. 2002), while the MCS brain demonstrates, or retains the potential for, a network response at any time such behaviors are evident (Schiff et al. 2005). This distinction can be correlated with both passive and active language paradigms on functional magnetic resonance imaging (fMRI), among many other methods (Giacino et al. 2014; Laureys and Schiff 2012). Indeed, of note is the use of volitional paradigms where patients are asked to respond to a command and imagine themselves playing tennis, swimming, or walking through a house (Owen et al. 2006; Bardin et al. 2011). This likely provides evidence of not only consciousness but a level of preserved integrative cerebral function typically correlated with much higher level behaviors in patients with intact motor systems (Schiff 2015).

These neuroimaging data cross-correlate with emerging electroencephalographic studies that indicate that MCS patients show preservation of electrical sleep–wake dynamics not seen in VS (Sitt et al. 2014). Beyond electroencephalography (EEG) and fMRI evidence, there is also emerging data that positron emission tomography (PET) imaging can meaningfully distinguish the vegetative from the minimally conscious state (Demerzi et al. 2015). The reinforcing nature of these cross-platform studies further strengthens the contention that there is a difference between the vegetative and minimally conscious states.

CLINICAL AND ETHICAL IMPLICATIONS

The intact cerebral networks present in MCS are also the predicate for emerging therapies. These interventions seek to activate these dormant or underactive circuits, most notably the anterior forebrain mesocircuit in which evidence supports the linkage of restored function to graded levels of recovery of consciousness (Schiff 2010).

To date, such activation has been achieved using neuroprosthetics with thalamic deep brain stimulation (DBS) (Schiff et al. 2007), drugs like amantadine (Giacino et al. 2012) and zolpidem (Brefel-Courbon et al. 2007), and more recently transcranial magnetic stimulation, which targets the same connected network within the anterior forebrain (Monti et al. 2016). These clinical effects are increasingly being correlated with changes in the underlying cerebral metabolism (Chatelle et al. 2014a; Schiff 2016). In the aggregate these data have profound clinical, ethical, and legal implications (Fins 2015; 2016).

Most fundamentally, the intact networks present in MCS point to the potential to perceive pain (Chatelle et al. 2014b). This calls for an immediate acknowledgment of the neuro-palliative care needs of members of this population (Fins 2008b; Fins and Pohl 2015; Fins and Master 2017), whose state is often conflated with insensate vegetative patients, often to their peril.

Structural changes seen longitudinally in the recovering brain, which may recapitulate important aspects of the normal developmental process, suggests that we should recast rehabilitation (Fins 2015) as an educational effort (Wright and Fins 2016). And if we accept that this process is temporally more akin to the education of children, then we need to reconsider public policies that dictate how much and how long this re-education process, essential to recovery, should be (Fins 2012). This calls for the reform of “improvement standards” that constrain access to adequate rehabilitation and ongoing care (Fins et al. 2016).

Finally, if patients can demonstrate a response to language through neuroimaging platforms and evidence of ongoing rewiring of key areas of the brain linked to language, we must strive to give their thoughts voice through ongoing efforts to restore functional communication. (Fins 2015). As the biology of their brain integrates, so too they should, as individuals, be reintegrated into the nexus of their families and communities, as consistent with the mandates of the Americans with Disability Act (Americans with Disabilities Act of 1990 1990) and the UN Convention on the Rights of Persons with Disability (Fins 2015; United Nations 2006). If overcoming the biological dis-integration caused by injury is a scientific and clinical objective (Fins 2017b), overcoming societal segregation is an ethical and legal imperative (Fins 2010; 2015).

IN SEARCH OF SILENT MINDS

Fischer and Truog have fixated on the metaphysical challenge of knowing the consciousness of another—a perennial question in philosophy—and in doing so neglected critical biological and clinical distinctions that can make a real-world difference for the lived experience of patients.

While our technologies are evolving and our efforts at discrimination are not perfect, the perfect should not be the enemy of the good. We need ask what sort of errors are worse than others. Like all things in medicine, we have to decide what sort of imprecision we are willing to accept. Is it worse to think consciousness is there, when it is not? Or to mischaracterize a conscious individual as unconscious?

What we fear most is the latter, a Type II error: failing to identify consciousness when it is present and to abridge future potentialities that current evidence indicates we cannot exclude. This risk is compounded when consciousness is taken out of the picture, as Fischer and Truog suggest. And that risk can be catastrophic for those conscious individuals mischaracterized, with grievious consequences for prognostication, pain management, neuro-palliative care, communication, community, and basic human rights.

Ultimately, this will be a question of sensitivity versus specificity, and the difference between clinical thinking and ethical reasoning. And in embracing the former, when it comes to patient care, we are reminded of the words of our teacher Fred Plum, who co-descibed the vegetative state in 1972 with Scottish neurosurgeon Bryan Jennett (Jennett and Plum 1972). Years ago in an unpublished and undated manuscript, Dr. Plum wrote of “absolute versus probabilities in ethical decisions. Probably the most difficult yet crucial point to be discussed is the one of relativism. When one can rely on the probabilities of an occurrence in reaching an ethical decision rather than await the definitive event, no matter how unlikely. Many ethicists hold to beliefs that are at least stated in absolute terms. By contrast, an increasing number of medical problems tend to be decided in relative terms” (Plum n.d.).

When it comes to taking care of patients, we can neither be purists nor absolutists. If we seek certainty in all we do, we will be unable to act and meet human needs. We will be captured by stasis and fixated.

We prefer to embrace the uncertainty, seek to diminish it incrementally and make progress in the service of those in need. While our efforts may be open to theoretical critique in some quarters, we prefer this over the critique of inaction or the neglect of a vulnerable population. For now, we will continue to be in search of consciousness and of silent minds (Fins and Schiff 2016).

ACKNOWLEDGMENTS

We are grateful to Lisa Mix and the New York Presbyterian Weill Cornell Medicine Archives for assistance with the Fred Plum Papers.

FUNDING

This commentary is funded by a grant to the Consortium for the Advanced Study of Brain Injury (CASBI), at Weill Cornell Medical College from the Jerold B. Katz Foundation. ▪

Notes

1. We use the vegetative state here and not the “unresponsive wakefulness syndrome” to avoid further confusion about nomenclature and given the rich history in medicine, bioethics and the law related to the vegetative state dating from Quinlan, Cruzan, and Schiavo. Furthermore, we believe that changing the name negates the seminal contributions of Jennett and Plum, who wrote about wakeful unresponsiveness in their seminal Lancet paper in 1972 first describing the condition (see Jennett and Plum 1972; Adams and Fins 2016).