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Fanfare — and Caution — Greet Report that Patients with Consciousness Disorders Understand and Respond to Language

ARTICLE IN BRIEF

Investigators reported that fMRI showed cortical activity in response to visual images in five patients who had consciousness disorders, indicating they could follow a command.

Some people who appear to have lost conscious thought and have been diagnosed with a persistent vegetative state (PVS) or minimally conscious state (MCS) may actually understand language but have no means of obvious expression. At least that is what Adrian Owen, PhD, of the MRC Cognition and Brain Sciences Unit of the University of Cambridge in the United Kingdom and Steven Laureys, MD, PhD, of the Coma Science Group at the University of Liege in Belgium, and their colleagues reported in a Feb. 3 study published online ahead of the print edition of the New England Journal of Medicine (NEJM).

The investigators used functional MRI (fMRI) to test whether the patients were responding willfully to mental-imagery tasks. Of 54 patients, five (10 percent) who had traumatic brain injury (TBI) could control their brain activity to provide the scientists with an electrical inkling — a specific pattern on the scan — that they can follow a command. Four of these patients had been previously diagnosed as being in a PVS— meaning they had no meaningful conscious thought — and one was in a MCS, that is, there was limited but deliberate conscious behavior. No responses were indicated in patients with non-TBI.

When they realized that these five people might actually be able to understand and respond to language they conducted lengthy clinical testing. Three of them had subtle signs of awareness, and their PVS diagnosis was changed to a MCS. One of these patients — three years after his initial TBI from a car accident —was able to learn the study design and mentally answer five of six questions with 100 percent accuracy. But in two of the five patients, clinical testing after the fMRI showed no evidence of voluntary behavior.

THE STUDY PROTOCOLS

Dr. Owen and his colleagues in the UK began their investigations in normal volunteers to see whether there was a way to capture a person thinking about something with an intention to match that thought with a “yes” or “no” answer. They found that asking an individual to think about playing tennis led to activation in the supplemental motor area of the brain. Thinking about moving around the house sparked activity in the spatial region, the parahippocampal gyrus.

In other experiments, they asked the volunteers to use one particular image to answer any “yes” questions and the other image to answer “no” and they had raters blinded to the answers guess, based on the activity on the scans, whether they said “yes” or “no.” They created brain maps or patterns that correlated with thoughts of playing tennis or having a person think about walking around their house.

The investigators compared scans from healthy controls to those of the patients who were unconscious to see whether there was evidence that their brains would show similar patterns.

RETHINKING THE DIAGNOSIS

This latest study may lead doctors to rethink how much certainty they can put to any diagnosis. In an editorial in the same issue of the NEJM, Allan H. Roper, MD, professor of neurology and executive vice chair of neurology at Brigham and Women's Hospital, said that even in this preselected population brain activity was infrequent “but it occurred often enough that it will now be difficult for physicians to tell families confidently that their unresponsive loved ones are not in there somewhere.'”

What that points to, he said, is that clinicians should diagnose the state of consciousness “only after detailed and repeated examinations,” and further that “cortical activation in response to meaningful stimuli and imagined activities indicates a likelihood of awakening.”

Few neurologists know this better than Nicholas Schiff, MD, associate professor of neurology and neuroscience at Weill Cornell Medical Center in New York City. He studied the brain of Terry Wallis, who in 2003 had emerged into a wakeful state 19 years after he was injured in a car accident and diagnosed with MCS. He regained fluent speech and some movement after his long silence and inactivity.

“I think these findings have extremely broad implications, not just for concerns about the accurate assessment of vast numbers of patients in custodial care situations whether they are in a vegetative state or a minimally conscious state. The results invite careful scrutiny of some patients in the context of any clinical encounter where we currently rely on behavioral assessment alone to identify consciousness,” said Dr. Schiff, whose landmark study was published in Nature in 2007.

Dr. Schiff, who was not involved in the NEJM study, said this study shows that it may be possible that “a patient who shows no evidence of communication can be identified to communicate or attempt to by these methods.”

He added: “It is important, however, to appreciate the complexity of these measurements and assessments of such severely brain injured patients. Obtaining this type of result is only the starting point and creates urgency to further investigate and assist such patients.”

What is so interesting, and what begs further investigation, said Dr. Schiff, is why a computer scan can pick up a person's thoughts but that the door is closed so tightly that the professional has no clue to that inner awareness. We'd like to know what accounts for the stunning dissociation of behavior and integrative brain function, he said. “I think we can be sure that as the biological answers underlying this question become clearer there may be a major shift in thinking that comes together from the collective efforts of investigators in this field.”

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DR. NICHOLAS SCHIFF: “I think these findings have extremely broad implications, not just for concerns about the accurate assessment of vast numbers of patients in custodial care situations whether they are in a vegetative state or a minimally conscious state. The results invite careful scrutiny of some patients in the context of any clinical encounter where we currently rely on behavioral assessment alone to identify consciousness.”

Such testing is not ready for re-evaluating the 100,000 or so people in this country alone languishing in nursing homes in such unconscious states, experts said. The ethical questions are enormous. “If you ask a patient whether he or she wants to live or die and the answer is die, would you be convinced that the answer was sufficient?” asked Joseph A. Fins, MD, chief of the medical ethics division at Weill Cornell. “We don't know that. We know that they are responding but what if they didn't understand the question.”