Deep brain stimulation for prolonged disorders of consciousness

Informed consent and autonomy

The issue of informed consent underscores some of the most contentious discussions in the present context. Clearly, patients with PDOC lack capacity to provide consent or dissent to treatment. Under the Mental Health Act 2005 (MCA), in the absence of a valid advance decision or a Lasting Powers of Attorney arrangement, all decisions regarding medical treatment for these patients must be made in their best interests. Interestingly, some authors have argued that informed consent is not only impossible to obtain but is in fact unnecessary in this situation. ¹¹ Their rationale was that VS is a special clinical condition produced by prior medical interventions, for which a “start-informed consent” would have already been available either in the form of the patient’s initial informed consent or a decision made by the physician in the case of emergency. By extension, this prior “start-consent” could effectively cover any subsequent “ordinary interventions” such as DBS. This creative line of thinking has yet to receive strong support, and it is generally agreed that any decision should be made on the basis of best interest.

Much has been written about the application of the “best interest test” in PDOC, but the use of DBS in this group of patients produces yet another set of problems. ¹² Firstly, while DBS, mechanical ventilation, and artificial nutrition and hydration (ANH) are all invasive treatments, DBS carries significantly higher risks of known as well as unknown complications. Secondly, while the withdrawal of ANH and mechanical ventilation is invariably fatal, the withholding of DBS is not. Thirdly, while ANH is unequivocally effective in sustaining life, the efficacy of DBS in PDOC has yet to be established. The issue at hand is therefore not so much about treatment futility or the sanctity of life, but whether and how complications and undesirable effects can be justified in these patients, whose interests, if any, remain unclear and debatable both legally and ethically. In this respect, PVS and MCS patients represent two distinct subgroups. Several common law cases, though mainly concerned with futility and non-treatment, may serve as useful references.

DBS for PVS

In the landmark case of Bland, the withdrawal of life-supporting treatments in a PVS patient was found not unlawful on the ground that their continuance was not in the patient’s best interest, and that the patient may not actually have any interest to speak of. ¹³ As such, the provision of any medical treatment may potentially amount to battery. However, the notion that a PVS patient has no interest purely because she lacks capacity is controversial. In the Ashan case, the family sought, successfully, to have a PVS patient being cared for at home rather than being sent to a nursing home, suggesting that the court does on occasions recognize the presence of at least non-medical interest in PVS patients. ¹⁴

Notwithstanding, the general rule post-Bland has been that the provision of medical treatment without prior consent in PVS patients would threaten patient autonomy and is not justified. This calls into question whether DBS, however well intentioned, is legally permissible and morally justified in these patients. In this regard, the case of NHS Trust v. J provides an interesting and relevant exception to the post-Bland rule. ¹⁵ J was a patient in PVS. His family’s request for the removal of ANH was initially not authorized; the court had instead asked for a therapeutic trial of Zolpidem, a hypnotics that had been shown to improve functions in some VS patients. Although the drug trial failed and ANH was subsequently withdrawn, the case illustrates that, in court, PVS patients do retain medical interests that could warrant the trial use of experimental therapy of yet unproven efficacy. The case of Simms v Simms similarly shows that experimental trial can be justified if it offers some hope where there is otherwise none. ¹⁶

Should DBS then be placed under the same category of experimental therapy and be permitted in PVS? Should the court then order patients to undergo such invasive treatment that carries definite risks? Or should patients who are otherwise “allowed to die” because of a lack of interest be allowed the chance to regain it? In justifying the use of invasive treatment in PVS patients, a distinction can be made between DBS, which has the theoretical potential of removing a patient from that clinical state, and ANH, which sustains a patient in it. The relevance and implications of this distinction hinges on diagnostic accuracy, prognostication and therapeutic efficacy.

While recovery from PVS is highly improbable, the necessary prediction of “permanence” lacks absolute certainty and has so far been relying on clinical assessment and past experiences with patients who had received supportive care only. Advanced diagnostic methods such as functional neuroimaging may, in the future, challenge the validity and legal implications of this diagnostic label. It can be argued that DBS, as a novel treatment targeted at the fundamental pathogenic process of PDOC, should be permitted given the possibility that it might alter the condition’s presumed course of permanence in at least some patients, thereby restoring some form of interests and rights in them.

Existing evidence, however, does not support the above line of argument. DBS has not been shown to provide benefits to any confirmed cases of PVS, and, more importantly, there is no sound scientific reason to suggest that it will. If one adopts the principle that, in order to justify a treatment in PVS patients, the treatment must “have the real prospect of curing it or at least palliating the life-threatening disease or illness from which the patient is suffering”, then DBS may be considered futile in PVS, its use is unlikely to be in a patient’s best interest, and therefore not justified as a routine or experimental therapy. ¹⁷

DBS for MCS

When compared with PVS, MCS has received somewhat different judicial treatment. In W v. M and others, the fact that the patient appeared to have some awareness and could possibly derive some benefits from being kept alive prompted the court to decide against treatment withdrawal. ¹⁸ Whether this provides legal grounds for allowing active interventions, such as DBS is debatable. ¹⁹ What is known is that MSC patients have preserved neural networks that is subject to activation and manipulation. Unlike PVS, natural recovery from MSC is not improbable, with close to a third of patients being able to improve. Available clinical evidence also suggests possible benefits from DBS. ⁹ To intervene accordingly with a view to further enhance recovery is consistent with the principle of beneficence. Some authors have in fact argued that “the patient’s inability to provide consent should not deter doctors from trying to remove those impairments that have prevented them from being able to participate in care decisions in the first place”. ²⁰ As such, in this author’s opinion, DBS is justified as a form of experimental therapy for MCS.

Potential harm of DBS in PDOC

DBS is an invasive therapy and an appraisal of its potential risks is necessary. As in all surgical treatments, the infliction of pain is a concern. Electrophysiological studies have demonstrated activities in the brain’s sensory cortex upon peripheral painful stimulation in PDOC patients, suggesting the possibility of pain sensation. ²¹ Regarding surgical complications of DBS, the overall incidence can be as high as 25%. ²² The commonest complications include bleeding, epilepsy and infection, the treatment of which may require re-operations. Harm may also result from side-effects due to the potency of the intervention itself. For instance, DBS is known to cause cognitive, psychiatric and behavioural problems in the treatment of Parkinson’s disease. Although these are of little immediate significance to PDOC patients, the possibility that DBS can cause long-term adverse effects must be entertained. Paradoxically, it is the primary goal of this treatment approach, namely, an improvement in awareness, that has attracted most controversies.

DBS in PDOC is sometimes seen as a “halfway technology” that addresses symptom manifestations without any attempt at curing the underlying disease. A historical example is the use of the iron lung in ventilating patients with poliomyelitis. It prolonged life but only at the high cost of the quality of life prolonged. In PDOC, DBS may improve cognitive or even physical functions while leaving patients severely disabled still. A frequently voiced criticism is that the treatment may create a state that is “worse than death.” The awareness of cognitive and physical impairments that are otherwise unperceived by the patient may become a significant burden that can outweigh any potential benefit. In fact, it may even be questioned if any of the so-called “benefits” (e.g. being able to recognize relatives) are genuinely patient-centred in nature. ²³ In this regard, PVS and MCS patients should be considered separately.

According to current understanding, PVS patients are unaware of their clinical states. DBS treatment, if successful, would impose on them a low state of awareness that is unlikely to improve further but which is, at the same time, highly unpleasant and, arguably, intolerable. For these patients whose primary “right-to-die” is already the focus of contemporary ethical discourse, it is important to ask if any improvement in consciousness is actually maleficent rather than beneficent. This contrasts with the case of MCS, in which patients already possess some awareness albeit only transiently. An intervention that can potentially propel them to a higher state of awareness and enhance their abilities to interact and communicate is more likely to be beneficial to and preferred by the patient. A duty can even be said to exist for physicians to remove them from a state of isolation to one that allows integration. The difficulty is that the level of restored consciousness could vary along a wide spectrum. A delicate balance between avoiding harm and providing preferred improvement can be difficult, if not impossible to predict and engineer.

Impact on personhood

There are also concerns about the potential impact of DBS on a person’s identity once consciousness has been restored. A detailed discussion on the philosophical concepts of identity, self and authenticity, and how they may relate to neurological diseases and treatment is beyond the scope of this paper. In theory, DBS may improve cognition to an extent that reaches the threshold of decision-making capacity. Should the patient then be asked to re-consent for the treatment? And what if the patient asks for the discontinuation of DBS, or even the withdrawal of life-sustaining treatments? As for any competent subjects, the patient’s regained right to self-determination must be respected, although the said decisions could be challenged on the ground that they have been made under the influence of DBS.

What matters most with regard to patient autonomy and what is also not known is how DBS will affect cognition and personal values. The ethico-legal dilemma in this situation is amply illustrated by the recent case of a Dutch patient who developed severe psychiatric symptoms following DBS. ²⁴ Under the effect of DBS, the patient became mentally incompetent but also found himself to have better quality of life than when the DBS was deactivated. He chose to remain in the former state at the expense of his mental competence and autonomy. One can but only imagine the challenges that may arise if similar situations occur with PDOC patients.

Cost and distributive justice

DBS is an expensive treatment. It entails the costs of the electrical implant, the labour of skilled surgeons and hospitalization. Some of the patients in PDOC may never improve and those who do may still require intensive medical care. On the other hand, cognitive improvement may enable a patient to communicate more effectively about otherwise undetectable symptoms; more timely treatment and prevention of complications can be provided. Improvement in mobility and swallowing may also reduce nursing costs. A detailed cost-benefit analysis is essential, and would necessitate prospective study using an appropriately sized cohort, and the proper weighting of fixed and variable costs for this specific group of patients. Ultimately, it is about whether limited medical resources are allocated fairly so that members of society will share healthcare benefits and burdens in a reasonable manner.

It may be argued that DBS in this group of patients is not justified unless there is convincing evidence of its benefit. Withholding expensive treatment in these patients would serve to promote access to scarce resources by others. However, from a duty ethics point of view, denying PDOC patients the chance of recovery, however slim and costly, speaks against the medical community’s duty to care. It may also cause secondary harm by propagating a societal neglect of disabled patients and minimizing the value of their lives. Since many of these patients have survived because of prior treatment (e.g. aggressive neurosurgical intervention), it can be argued that the medical community (and society as a whole) does owe a duty to continue to innovate and care for them. From a utilitarian point of view, the key consideration is how to maximize public utility, and patient selection should be targeted at patients in whom DBS is most likely to provide, for example, more quality-adjusted life years. Based on forgoing discussions, DBS can be said to be justifiable in MCS patients but less so, if at all, in PVS patients. In future, patient selection may be further facilitated by advanced functional neuroimaging, although the latter is not without its limitations. ⁶ Another potential concern is that DBS is, and is likely continue to be, delivered in an inequitable manner, in that its high cost would limit its use to patients from affluent countries and those with health insurance.

Research

Whether the use of DBS in PDOC should be regarded as research or experimental therapy is subject to debate. According to the World Medical Association Declaration of Helsinki, any new intervention must be tested against the best proven intervention. ²⁵ While this may be possible and desirable in cases of Parkinson’s disease, where effective medical treatment exists, it is not feasible for PDOC, for which there is no existing effective treatment.^2,5 In the UK, the MCA 2005 provides that, as a form of research, DBS can be authorized for use in incompetent subjects only if it will produce some conceivable benefits. It is therefore critical for investigators to first be able to measure patient outcome in both clinical and ethical terms. Unfortunately, reported studies tended to rely on improved awareness or physiological changes as outcome measures; patients’ subjective responses were not subject to evaluation. The inability to know in the first instance what might actually constitute benefit or burden poses an unusual and significant challenge in terms of clinical trial design and ethics oversight. This is not often discussed and may call into question the ethicality of enrolling PDOC patients in related clinical trials.

The fact that MCS patients are more likely to “improve’ with DBS may render them more suitable as research subjects. However, some authors have argued that experimental surgery such as xenotransplantation may also be justified in PVS patients for the very reason that they lack all interest. ²⁶ The fact that DBS is likely to be ineffective in PVS patients should not, according to those authorities, deter researchers from including them in “proof of principle” studies (and indeed it had not). To protect these vulnerable patients with impaired decision-making capacity, the United States National Bioethics Advisory Commission recommended that neuromodulation research should not be allowed when there is more than minimal risk of harm and no demonstrated prospect of direct medical benefit. ²⁷ This raises questions about including PDOC patients as research subjects for an invasive surgical treatment such as DBS. While this risk-aversion approach has it own merit, it may hamper advances in neuroscience and deny potential medical benefits to patients whom the regulation seeks to protect. ²⁸

It must be emphasized that available clinical evidence was mainly derived from head-injured patients; the tendency to over-generalize it to other disease groups must be resisted. Another technical issue is the choice of therapeutic window. For MCS patients, it would be preferable to include only those who have been in MCS for at least one year to avoid interfering with the natural recovery process. The pay-off is that such “delayed” treatment is less likely to be effective. Furthermore, eager researchers can inadvertently put desperate family members under pressure or induce therapeutic misconception. To counter this, a clear distinction between MCS and PVS patients is critical but is unfortunately rarely entertained. The involvement of commercial companies to support the use of expensive devices such as DBS must also be addressed since potential conflict of interest can undermine the validity and acceptability of research findings. Lastly, research protocol must sufficiently cater for situations where the patient, once having regained capacity, may request to be withdrawn from the study and for the DBS to be discontinued. From a moral point of view, investigators may also be required to bear the clinical and fiscal responsibilities to continue to care for their research subjects following DBS implantation as opposed to “abandoning” them to, say, community hospitals that lack the necessary expertise. ²⁹