New technique spots patients misdiagnosed as being in ‘vegetative state’

November 9, 2011

All the patients had the same terrible diagnosis: brain damage that marooned them in a “vegetative state” — alive but without any sense of awareness of themselves or the world around them.

But then an international team of scientists tried an ambitious experiment: By measuring electrical activity in the patients’ brains with a relatively simple technique, the researchers attempted to discern whether, in fact, they were conscious and able to communicate.

In most of the cases, there was nothing — no signs that any sentience lingered. But then one man, and another, and, surprisingly, a third repeatedly generated brain activity identical to that of healthy volunteers when they were asked to imagine two simple things: clenching a fist and wiggling their toes.

The findings, reported online Wednesday by the journal the Lancet, provide startling — and in some ways disturbing — new evidence confirming previous indications that a significant proportion of patients diagnosed as being vegetative may in fact be aware.

But, most important, the widely available, portable technology used in the research offers what could be the first practical way for doctors to identify and finally communicate with perhaps thousands of patients who may be languishing unnecessarily in isolation. Doctors could, for example, find out whether patients are in pain.

“You spend a week with one of these patients and at no point does it seem at all they know what you are saying when you are talking to them. Then you do this experiment and find it’s the exact opposite — they do know what’s going on,” said Damian Cruse, a postdoctoral neuroscientist at the University of Western Ontario in Canada who helped conduct the research. “That’s quite a profound feeling.”

The results and similar findings could also provide crucial insights into human consciousness — one of the most perplexing scientific puzzles — and lead to ways to better provide diagnoses and possibly rehabilitate brain-injury patients, the researchers said.

“Can you imagine spending years without being able to interact with anyone around you?” Cruse said. “We can ask them what it’s like to be in this condition. Do they know where they are? Do they know who is around them? What do they need?’ This will lead to very profound implications.”

Other experts, while praising the research, cautioned that much more work is needed to confirm the findings and refine the technology.

“Laypeople will interpret these experimental results as a clinical test, and they are not ready to be used that way,” said Nicholas D. Schiff, a neurologist at the Weill Cornell Medical College in New York.

As many as 20,000 Americans are in a vegetative state, meaning they are alive and awake but without any apparent sense of awareness, and 100,000 to 300,000 are in a related condition known as a minimally conscious state, in which they exhibit impaired or intermittent awareness. A growing body of evidence in recent years has indicated that a significant proportion might have more awareness than had been thought.

“It doesn’t mean all vegetative patients are aware. It is only some. But when you think of the number of patients that there are around the world in this situation, it is quite a lot,” said Adrian M. Owen, a neuroscientist at the University of Western Ontario who is the senior researcher involved in the work.

In 2006, Owen and his colleagues described a young woman thought to be in a vegetative state. Her brain responded identically to a normal brain when scanned with functional magnetic resonance imaging (fMRI) as researchers asked her to imagine playing tennis or exploring her home. The case electrified neuroscientists. But it remained unclear whether it was a fluke.

Then in February 2010, Owen’s team reported similar testing on 23 vegetative patients and 31 minimally conscious patients. Five repeatedly fired their brains in precisely the same way as normal volunteers as they underwent
fMRIs while being asked to imagine hitting a tennis ball and wandering through their homes. One patient was able to answer yes or no to a series of questions by thinking about tennis for yes and touring his home for no.

But fMRIs are expensive and difficult to perform, and the equipment is not portable. “Many of these patients are vulnerable, and it’s difficult to move them around. So it’s difficult to get access to this technology,” Owen said.

So the researchers decided to try using a technique called electroencephalography (EEG), a time-tested way to precisely measure activity in different parts of the brain that is relatively easy and portable.

“We can take it to the patient, which effectively means that almost any patient in the community, in care homes and residential homes and hospitals, we can get to them,” Owen said. “We can establish how many of those patients are conscious.”

Between July 2010 and June 2011, the scientists tested 16 patients ages 14 to 63 at Addenbrooke’s Hospital in Britain and the University Hospital of Liege in Belgium who had been declared in a vegetative state. For some, the diagnoses had come eight years ago; for others, within the previous month. They had suffered head injuries in a car crash or some other accident, or oxygen had been cut off to their brains, such as from a stroke.

The scientists asked the subjects to imagine making a fist with their right hand and then relaxing it and wiggling all their toes on both feet and then relaxing them. Twelve healthy volunteers were tested for comparison imagining the same things.

Three of the 16 — a surprisingly high 19 percent — generated normal EEG responses hundreds of times in response to the requests. The scientists could find nothing else unusual about them. All were men, ages 29, 35 and 45, who had been declared in a vegetative state three, nine and 23 months earlier.

“It’s like the scenario we’ve seen in medical dramas where the doctor takes the hand of a patient on the side of the road and says, ‘If you can hear me, squeeze my hand,’ ” Owen said. “What we’ve done is exactly the same thing, except we know they can’t move, so we ask them to respond using nothing but their brains. If someone on the side of the road could squeeze your hand more than 200 times, I don’t think anyone would have any doubt that they know where they were and what was going on.”

Owen acknowledged that the findings are both exciting and disturbing.

“We’re all disturbed at the idea of being locked or trapped. It’s like being buried alive,” Owen said. “We’d rather hope that doesn’t exist. But that’s not a reason to turn away from it. It’s really a wake-up call to do something about it.”

Finding a way to communicate with brain-damaged patients has long been a goal of neuroscientists. It has also been the subject of literature and films, including the 2007 film “The Diving Bell and the Butterfly,” which told the story of French editor Jean-
Dominique Bauby. Bauby, paralyzed in a “locked-in syndrome” by a stroke, could communicate only by blinking his left eye.

The research inevitably raises questions about patients such as Terri Schiavo, a Florida woman in a persistent vegetative state whose family’s dispute over whether to discontinue her care ignited a national debate over the right-to-die issue and congressional intervention in 2005. Schiavo’s brother, Bobby Schindler, said the new study highlights the limits of medicine in providing an accurate diagnosis.

“Regrettably, Terri was never afforded these types of exams,” Schindler wrote in an e-mail to The Washington Post. “Such testing could not have hurt Terri but could have helped her.”

Schindler and others called for a reconsideration of such diagnoses.

“These findings only reinforce our family’s contention that the PVS diagnosis needs to be eliminated — particularly given the fact that it not only dehumanizes the cognitively disabled, but it is being used in some instances to decide whether or not a person should live or die, as it was used in Terri’s case. None of us deserves to be deprived of food and water,” he said.

But experts stressed that the research does not indicate that many patients in vegetative states are necessarily aware or have any hope of recovery.

“Expanded use of EEGs in this population will lead to a new class of very thorny questions,” said Kenneth W. Goodman, a University of Miami bioethicist. “It would be very sad indeed if this and related research engendered doubts that lead to prolonged treatment of the large majority of patients who are accurately diagnosed as vegetative.”

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