July 2, 2008 — New techniques that allow imaging of so-called "default networks" are helping to differentiate patients in a minimally conscious state or with locked-in syndrome (LIS) from those in a coma or persistent vegetative state, new research shows.
A default network is defined as a set of areas in the brain, including the posterior-cingulate/precuneus, anterior-cingulate/mesiofrontal cortex, and the temporoparietal junctions, that show more activity on functional MRI (fMRI) at rest than during tasks that require attention.
In the new study, researchers led by Steven Laureys, MD, PhD, head of the Coma Science Group at the Cyclotron Research Center, University of Liège, in Belgium, showed significant differences in default-network activity between both healthy people and those in a minimally conscious state vs patients in a coma or persistent vegetative state.
"We could identify a correlation of the integrity of that network and the level of consciousness," Dr. Laureys told Medscape Neurology & Neurosurgery. "It is obviously most intact when you are normal; decreases when you look at minimally conscious, vegetative coma; and again looks normal in patients with locked-in syndrome."
In a separate presentation, these researchers used a quality-of-life questionnaire altered to accommodate patients with LIS, a combination of quadriplegia and anarthria that does not allow patients to speak or move despite being fully conscious. A vast majority, 92%, of these patients "never or seldom" think of suicide and report a meaningful quality of life.
Both reports were presented recently at the 18th Meeting of the European Neurological Society, in Nice, France.
Default Networks
Besides being less active during tasks that require attention, the default network has been shown to be involved in higher cognitive functions such as self-related processes, emotion, and memory, the authors note. Recent studies have shown it is possible to reliably identify the network in healthy volunteers in the absence of any task using resting-state connectivity analyses, they write.
In the present study, first author Mélanie Boly, MD, a researcher at the Belgian national Funds for Scientific Research, and colleagues in the Coma Science Group used fMRI to assess default-network activity in the resting state in 13 acutely brain-damaged patients and 12 healthy controls. Brain-damaged patients included 1 in brain death, 5 in a coma, 3 in a vegetative state, 3 in a minimally conscious state, and 1 with locked-in syndrome.
Significantly less activity was observed within all areas of the default network for the coma and vegetative-state patients than controls, they report, while minimally conscious and LIS patients were not significantly different from controls. "All default network-area connectivity was shown to be clearly correlated with the degree of clinical-consciousness impairment of the patients, ranging from coma, to vegetative state, minimally conscious state, and locked-in syndrome," they write.
No cortical spatial map could be identified in the patient with brain death.
If this approach is validated in a larger number of patients, imaging of default networks may be of some diagnostic or even prognostic clinical use. "The first aim is to show that this network is different when we take patients who are well-studied behaviorally and with other tools, and how that it is helpful in diagnosis," Dr. Laureys noted. "This is done now, but we need many more; when we have really big samples, then we can say something about the outcome."
Although default activity is a "hot topic" now, he added, "it's a bit controversial what it really means. For some it doesn't mean anything, just an artifact related to changes in breathing and blood pressure and heart rate," he said. "Herealso, studying these patients in coma helps us better understand what it means even in normal people."
In a press statement from the European Neurological Society (ENS), Gustave Moonen, MD, also from the University of Liège and president-elect of the ENS, pointed out that these researchers showed significant differences in default-network activity between healthy controls and those in various states of consciousness. "However, much work remains to be done so that the prognostic value of this and other imaging procedures can assist in more exact diagnosis of patients after coma."
Surveying LIS Patients
In a separate presentation in Nice, Dr. Laureys's team, with first author Marie-Aurélie Bruno, a PhD student in the Coma Science Group, also funded by the Belgian Funds for Scientific Research, examined quality of life in patients with locked-in syndrome. "We tend to consider this life, which is the most important motor deficit that is still compatible with life, as not worth living," Dr. Laureys said. "But very few studies have asked these patients themselves how they feel, so this is a study where we're trying to answer that question."
LIS patients have also classically been considered unable to make decisions for themselves because of cognitive deficits, but to date, neuropsychological testing of these patients has not been possible.
For this study, they adapted classical testing batteries so that patients could answer using a blink of the eye to indicate responses to tests of attention, short-term memory, intelligence, and language. Quality of life was assessed using the Anamnestic Comparative Self Assessment scale.
Responses were obtained in 65 LIS patients; the mean duration in this condition was 9 + 5 years. In 41% of these cases, they note, it was a relative of the patient and not the treating physician who first realized that the patient was conscious and could communicate with eye movements.
Results of the quality-of-life questionnaire indicated that the "vast majority" of patients, 92%, never or only occasionally had suicidal thoughts and more than half, 54%, wanted resuscitation to be attempted in the event of a cardiac arrest. Of the patients, 55% never considered or discussed euthanasia, although a small group, about 5%, reported they wanted euthanasia at the time of the study.
The quality-of-life scores were in fact not significantly different from those of healthy matched controls (1.02 + 3.05 vs 1.69 + 1.82), they write.
Patients with LIS cause by a brain-stem lesion have intact cognition, Dr. Laureys said, "so the patients themselves can and should make decisions about treatment options or end-of-life decisions."
These results were a surprise, even to his group, he added, who have worked with these patients for a long time. "Clinicians should realize that quality of life often equates with social rather than physical capacity," they conclude. "It's important to emphasize that only the medically stabilized, informed LIS patient is able to accept or to refuse life-sustaining treatment."
This work was done in collaboration with the French Association for Locked-in Syndrome, an organization launched after the success of the book The Diving Bell and the Butterfly, now a successful film, written by Jean-Dominique Bauby, perhaps the most famous LIS patient. Bauby wrote the book 1 letter at a time, blinking his left eyelid to indicate the letter he wanted as an assistant recited the alphabet. Bauby died of pneumonia soon after his book was published, but the association now has a membership of more than 300 LIS patients, Dr. Laureys said.
"Contrary to what many lay people, and also many doctors, would assume, many LIS patients find meaning and quality in their lives," Dr. Moonen said of these findings in the ENS statement. "Patients who suffer locked-in syndrome should not be denied the right to die, but even less should they be denied the right to the best possible care in living."
18th Meeting of the European Neurological Association: Abstracts 179, 111. Presented June 9, 10, 2008.
Medscape Medical News © 2008 Medscape
Cite this: Susan Jeffrey. Imaging Default Networks Differentiates Minimally Conscious States from Coma - Medscape - Jul 02, 2008.
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