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Awareness in vegetative patients

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“A man who was presumed to be in a vegetative state for five years has answered questions using his thoughts alone”, reported The Times. It said the research could allow some patients who are “locked in” by brain injuries to communicate.

The news is based on a three-year study in 54 patients in a vegetative or minimally conscious state. The patients’ brains were scanned with a technique called functional magnetic resonance imaging (fMRI) to detect signs of awareness. In one man, previously thought to be in a persistent vegetative state, the researchers were able to elicit the correct responses to five out of six questions.

These results confirm that some patients who meet the current criteria for being in a vegetative state are diagnosed incorrectly and retain thinking and awareness. It should be highlighted that this occurred in only one of the patients tested, and it is unknown how many people are likely to be in the same state.

The researchers say there is a high rate of error (approximately 40%) in diagnosing this group of patients. It appears the use of fMRI scanning may add another layer of safety in the diagnosis of consciousness following brain injury. The potential that the technique will lead to better care for patients in vegetative states, for example by allowing them to communicate their wishes, will need further research.

Where did the story come from?

This study was carried out by Dr Martin Monti and colleagues from the Medical Research Council Cognition and Brain Sciences Unit, the Impaired Consciousness Study Group and the Division of Academic Neurosurgery, all in Cambridge, along with international colleagues from the University of Liege and University Hospital of Liege in Belgium. The study was supported by several organisations and received grants from the Medical Research Council and the European Commission.
The study was published in the peer-reviewed New England Journal of Medicine.

Some newspapers have incorrectly used the terms ‘coma’, ‘vegetative state’ and ‘locked in’ outside their technical definitions. For example, it is wrong to say that the study shows that “patients in ‘vegetative’ state can think and communicate” or “that one-in-five patients in a persistent vegetative state may be able to communicate,” as the Telegraph does. The number of people who may be able to communicate usefully may be quite small. The newspapers reported that there are normally fewer than 100 patients in the UK in a permanent vegetative state (PVS) at any time.

What kind of research was this?

The aim of this study was to investigate ways of improving diagnostic testing for vegetative and minimally conscious states. This built on the researchers’s previous research. This has shown it is possible for someone tested using conventional movement responses, and who meets the clinical criteria for being in a vegetative state, to have intact awareness when tested with fMRI.

The researchers wanted to investigate how many patients in a vegetative or minimally conscious state could reliably and repeatedly modulate their brain activity as shown by their fMRI responses. The researchers say the ability to do this suggests awareness. They also wanted to test if these patients could communicate yes or no responses by modulating their brain activity without training and without the need for any movement.

The researchers say that awareness distinguishes minimally conscious patients from those in a vegetative state and has important healthcare, ethical and legal implications. The usual tests to distinguish between these conditions involves movement responses. However, these methods face several problems, such as muscle weakness, inconsistent responses and a difficulty distinguishing between automatic reflexes and voluntary movement. They say there is a high rate of error (approximately 40%) in the diagnosis in this group of patients.

What did the research involve?

This was an experimental study with cross-sectional analysis in 23 patients in a vegetative state and 31 patients in a minimally conscious state. The patients had all been referred to two hospitals that are major referral centres for this type of brain injury. These hospitals already routinely evaluate brain injury patients with fMRI to assess their performance on motor and spatial imagery tasks.

The researchers say that the classification of conscious disorders can be complex.

Coma

After severe head injury patients may enter a state of coma, defined as a profound state of unconsciousness in which they cannot respond normally to pain, light or sound and do not have sleep-wake cycles.

Vegetative state

Patients may then progress to a vegetative state following coma. In this state, they are ‘awake’ in the sense they have sleep-wake cycles, but without detectable awareness. As the time spent in a vegetative state increases, the chance of regaining awareness decreases.

Persistent vegetative state

After a period in a vegetative state, patients are said to be in a persistent vegetative state. Some stay in this state long-term with little chance of recovery.

Minimally conscious state

Others can progress to a minimally conscious state, and show inconsistent but reproducible signs of awareness, tested by behavioural responses to stimuli, including the ability to follow commands. However, they remain unable to communicate.

In this research, two imagery tasks were first tested in 16 healthy control subjects (nine men and seven women) with no history of neurologic disorders. In the motor imagery task, participants were asked to imagine they were playing tennis. In the spatial imagery task, they were asked to imagine walking from room to room in their home and to visualise all that they would ‘see’ if they were there. Carrying out these tasks stimulates different areas of the brain that can be viewed using an fMRI scanner. For example, the motor cortex area of the brain is responsible for movement, and when a person thinks about movement this will show up on the scan. These tasks were also performed on all of the patients referred.

In a communication task, the control subjects were asked to try to answer questions by thinking about the two tasks. They were asked to think about tennis (motor imagery) for each time they wanted to say yes and about checking the rooms in the house (spatial imagery) if they wanted to say no.
The communication test was given to all healthy control patients. It was also given to the one patient who had been able to modulate his brain activity in the first two imagery tasks.

What were the basic results?

Of the 54 patients enrolled in the study, five were able to wilfully modulate their brain activity. Three of these patients  demontratedsome sign of awareness in bedside testing, but the other two showed no voluntary behaviour such as movement that could be detected by means of clinical assessment.

One of the patients who was able to wilfully modulate his brain activity was given the communication task. The fMRI scans showed brain activity giving the correct answer to five out of six yes or no-type questions. The researchers say that it still remained impossible to establish any form of communication with this man.

Among the 23 patients who had been given a diagnosis of being in a vegetative state on admission, four demonstrated awareness in the mental imagery tests suggesting that they had been misdiagnosed.

How did the researchers interpret the results?

The researchers say that their results show that movement can be so impaired that bedside tests based on the presence or absence of a behavioural response may not reveal awareness, regardless of how thoroughly and carefully they are administered.

They say that in these patients functional MRI complements existing diagnostic tools by providing a method for detecting covert signs of residual thinking and awareness.

Conclusion

These results suggest that some patients, who meet the current criteria for being in a vegetative state, are diagnosed incorrectly and retain thinking and awareness. False-negative (misdiagnoses due to a test being negative when someone has a condition) and false-positive results (misdiagnoses due to a test being positive when someone does not have a condition) are possible with any test. Combining tests can improve their accuracy and it is possible that the combination of bedside tests and fMRI scans would provide improve diagnostic accuracy.

There are some points to note:

  • As only one patient in a vegetative state was tested for his communication ability, this will need to be repeated in others to find how many false negative and false positives this test has. The researchers say that even in healthy volunteers false negatives when using fMRI imaging are common, and therefore negative findings cannot be used as evidence for a lack of awareness. In this study, negative responses were shown by 49 of the 54 patients and it is not clear if this is due to low sensitivity of the test in detecting awareness, or if the patients were sometimes unconscious during scanning.
  • Only five of the six questions elicited a correct response from the patient in a vegetative state. The last question was not answered, the researchers say that they cannot tell from the lack of brain activity if the patient fell asleep, did not hear the question, elected not to answer it or lost consciousness.

The patient in this study and another woman described by the same researchers in 2006, suggest that, though rare, there are cases where people thought to be in a vegetative state are aware to some degree.

This study suggests a method by which some of these non-communicative patients, including those diagnosed as vegetative, minimally conscious, or locked in, may in the future be able to use their residual cognitive capabilities to communicate their thoughts to those around them.

Links to the headlines

Coma victim talks via brain scanner. Financial Times, February 4 2010

Patient in a vegetative state ‘talks’ to scientists. Daily Mail, February 4 2010

Think tennis for yes, home for no: how doctors helped man in vegetative state. The Guardian, February 4 2010

Patients in ‘vegetative’ state can think and communicate. The Daily Telegraph, February 4 2010

Patient ‘locked in’ by brain injury answers question using thoughts alone. The Times, February 4 2010

Brain scan shows awareness in vegetative patients. BBC news, February 4 2010

Scientist on ‘brain scan breakthrough’. BBC news, February 4 2010

I think..I’m alive. The Sun, February 4 2010

Links to the science

Mont MM, Vanhaudenhuyse A, Coleman MR, et al. Willful Modulation of Brain Activity in Disorders of Consciousness. NEJM 2010 February 3

 

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