Thursday, August 2, 2007

Implant boosts activity in injured brain

Brain function has been improved in a patient who was in a minimally conscious state, by electrically stimulating a specific brain region with implanted electrodes. The achievement raises questions about the treatment of other patients who have been in this condition for years, the researchers say.

Patients in a minimally conscious state, often the result of severe brain trauma, show only intermittent evidence of awareness of the world around them. Typically, they are assumed to have little chance of further recovery if they show no improvement during their initial 12-month rehabilitation programme.

In the latest case study, neuroscientists describe how they implanted electrodes in the brain of a 38-year-old man who had been in a minimally conscious state for more than six years following a serious assault. By electrically stimulating a brain region called the central thalamus, they were able to help him name objects on request, make precise hand gestures, and chew food without the aid of a feeding tube...

Nicholas Schiff of Weill Cornell Medical College in New York, and his colleagues chose the patient because they believed his condititon was due to impairment of the arousal system, and that despite considerable damage to his cerebral cortex, many essential areas were preserved.

"There will be a subset of patients who are responsive to this approach," says Schiff. But he adds that patients with different brain injuries may not benefit from electrostimulation. "Not every patient in a minimally conscious state will fit this profile," Schiff says, and it is difficult for neurologists to identify those patients who will show recovery.

Nevertheless, the case shows that many patients currently seen as beyond hope of rehabilitation might benefit from the results of further research. ..."Although based on a study of only a single patient, it suggests that DBS may be adapted to benefit at least some patients in the minimally conscious state. And it emphasizes that improvements can be made by patients even long after an injury.

"Although we do not know precisely which brain connections are important, we may expect that some specific connections must be intact for DBS to have a beneficial effect."


Haul out the qualifiers: the study was of one patient; the patient's status was "minimally conscious" and not "persistent vegetative state"; the subject's cortex showed capacity for activity. etc. There is still much to learn about the nature of the subset of patients potentially responsive to this intervention. There is an enormous risk that a result of this sort will be hyped and overgeneralized for political purposes and will stimulate unrealistic near-term hopes likely to be disappointed.

All that said, this report serves as a critical reminder of the tendency of some, including physicians and scientists, to overstate their knowledge of what is not possible--a tendency perhaps particularly in evidence in the domain of brain function. Much is not understood, and the lack of knowledge is not equivalent to knowledge of "lack". Some of the neurologists who have been prominent in public controversies over the definition of death (particularly advocates of "higher brain" or "higher function" proposed definitions) or the poorly framed "right to die" have been, uh, imprecise in acknowledging the limits of their (and our collective) expertise, and others (mostly non-physicians) have played fast and loose in their formulations, dropping critical qualifications and making unwarranted generalizations in support of their advocacy positions. There is a professional bioethics literature on these issues, and some scholars have long made the point that discussions of impaired brain function must be scrupulous in their honesty and candor about the limits of our knowledge and prognostic abilities.

None of this, of course, answers the question of what level of certainty is necessary to resolve issues of public policy, at the bedside, in courts, or in legislative and regulatory arenas. That is not primarily a scientific question.

The original abstract from Nature follows:
Widespread loss of cerebral connectivity is assumed to underlie the failure of brain mechanisms that support communication and goal-directed behaviour following severe traumatic brain injury. Disorders of consciousness that persist for longer than 12 months after severe traumatic brain injury are generally considered to be immutable; no treatment has been shown to accelerate recovery or improve functional outcome in such cases1, 2. Recent studies have shown unexpected preservation of large-scale cerebral networks in patients in the minimally conscious state (MCS)3, 4, a condition that is characterized by intermittent evidence of awareness of self or the environment5. These findings indicate that there might be residual functional capacity in some patients that could be supported by therapeutic interventions. We hypothesize that further recovery in some patients in the MCS is limited by chronic underactivation of potentially recruitable large-scale networks. Here, in a 6-month double-blind alternating crossover study, we show that bilateral deep brain electrical stimulation (DBS) of the central thalamus modulates behavioural responsiveness in a patient who remained in MCS for 6 yr following traumatic brain injury before the intervention. The frequency of specific cognitively mediated behaviours (primary outcome measures) and functional limb control and oral feeding (secondary outcome measures) increased during periods in which DBS was on as compared with periods in which it was off. Logistic regression modelling shows a statistical linkage between the observed functional improvements and recent stimulation history. We interpret the DBS effects as compensating for a loss of arousal regulation that is normally controlled by the frontal lobe in the intact brain. These findings provide evidence that DBS can promote significant late functional recovery from severe traumatic brain injury. Our observations, years after the injury occurred, challenge the existing practice of early treatment discontinuation for patients with only inconsistent interactive behaviours and motivate further research to develop therapeutic interventions.

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