Functional PET Flags Recovery Potential in Vegetative Patients

Megan Brooks

April 17, 2014

Functional brain imaging with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) may help determine whether a patient in a vegetative state has the potential to recover consciousness, according to a new study.

"Our findings suggest that PET imaging can reveal cognitive processes that aren't visible through traditional bedside tests, and could substantially complement standard behavioural assessments to identify unresponsive or 'vegetative' patients who have the potential for long-term recovery," lead author Steven Laureys, PhD, from the Coma Science Group, University of Liège in Belgium, said in a Lancet news release.

"We showed that in about a third of the patients we can find signs of consciousness that we didn't expect based on the bedside examination," Dr. Laureys said in an interview with Medscape Medical News.

The study was published online April 16 in the Lancet.

Unexpected Signs of Consciousness

Detecting unambiguous signs of consciousness in severely brain-damaged patients is challenging, the authors note. Up to 40% of patients with unresponsive wakefulness syndrome (vegetative state) may be misdiagnosed with bedside clinical examinations.

Dr. Laureys and colleagues tested the hypothesis that neuroimaging with FDG-PET at rest and functional magnetic resonance imaging (fMRI) during mental tasks can complement bedside clinical detection of consciousness and prediction of recovery.

The study included 41 patients with unresponsive wakefulness syndrome, 81 in a minimally conscious state, and 4 with locked-in syndrome (a brain-damaged yet conscious control group). Including patients with locked-in syndrome "allows internal validity to be controlled by verifying the ability of the tests to detect awareness in fully conscious but physically incapacitated patients," they explain.

The researchers calculated the diagnostic accuracy of both imaging methods, using the standard Coma Recovery Scale-Revised (CRS-R) diagnosis as reference.

They report that FDG-PET had high sensitivity for identifying patients in a minimally conscious state (93%; 95% confidence interval [CI], 85% - 98%) and high agreement with behavioral CRS-R scores (85%; 95% CI, 77% - 90%).

fMRI during mental activation tasks was less sensitive at diagnosis of a minimally conscious state (45%; 95% CI, 30% - 61%) and had lower overall agreement with CRS-R scores (63%; 95% CI, 51% - 73%) than PET imaging.

PET correctly predicted outcome in 75 (74%; 95% CI, 64% - 81%) of 102 patients, and fMRI in 36 (56%; 95% CI, 43% - 67) of 65 patients.

Of note, the authors say 13 (32%) of 42 patients diagnosed as unresponsive by CRS-R showed brain activity suggestive of minimal consciousness on at least 1 neuroimaging test, and 9 of these patients (69%) subsequently recovered consciousness.

"Repeated testing with the CRS-R complemented with a cerebral FDG-PET examination provides a simple and reliable diagnostic tool with high sensitivity towards unresponsive but aware patients. fMRI during mental tasks might complement the assessment with information about preserved cognitive capability, but should not be the main or sole diagnostic imaging method," Dr. Laureys added in the journal news release.

In talking with Medscape Medical News, Dr. Laureys acknowledged that neuroimaging tests "are expensive, but the care of these patients who can survive for many decades is also very expensive, so to me it's definitely worthwhile to use these neuroimaging techniques to reduce the uncertainty regarding the diagnosis and prognosis of these very challenging patients."

"We need to think how we can make this more widely available and also, I think, develop cheaper tests that are portable and will probably be [electroencephalography]-based. The problem of quantifying consciousness is so difficult that I think it's important to combine different complementary technologies, and this is a first step. Others will need to confirm it or not," Dr. Laureys said.

The authors point out that the study was done in a specialist unit focusing on the diagnostic neuroimaging of disorders of consciousness, and therefore roll-out might be more challenging in less-specialist units.

Serves as a Signpost

In an accompanying comment in the Lancet, Jamie Sleigh, MD, from the University of Auckland, New Zealand, and Catherine Warnaby, PhD, from the University of Oxford, United Kingdom, note that in patients with substantial cerebral edema, "prediction of outcome on the basis of standard clinical examination and structural brain imaging is probably little better than flipping a coin."

In the future, we will probably look back in amazement at how we were ever able to practice without it.

Based on this study, they write, "it would be hard to sustain a confident diagnosis of unresponsive wakefulness syndrome solely on behavioural grounds, without PET imaging for confirmation."

This study, they conclude, "serves as a signpost for future studies. Functional brain imaging is expensive and technically challenging, but it will almost certainly become cheaper and easier. In the future, we will probably look back in amazement at how we were ever able to practise without it."

The study was funded by The Belgian National Funds for Scientific Research, Fonds Léon Fredericq, the European Commission, the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action, the University of Copenhagen, and the University of Liège. The authors and commentators have disclosed no relevant financial relationships.

Lancet. Published online April 16, 2014. Article abstract, Comment extract


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