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FMRI Accurately Predicts which Patients can Recover from Vegetative State

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According to new research published in The Lancet, a functional brain imaging (fMRI) method known as positron emission tomography (PET) is a promising tool for determining which severely brain damaged individuals in vegetative states have the potential to recover full consciousness.

It is the very first time that researchers have tested the diagnostic accuracy of fMRI techniques in clinical practice.


"Our findings suggest that PET imaging can reveal cognitive processes that aren't visible through traditional bedside tests, and could substantially complement standard behavioral assessments to identify unresponsive or "vegetative" patients who have the potential for long-term recovery," said study leader Professor StevenLaureys from the University of Liége in Belgium.


In gravely brain-damaged individuals, evaluating the level of consciousness has proved quite difficult. Conventionally, bedside clinical examinations have been utilized to determine whether patients are in a minimally conscious state (MCS), in which there is some evidence of awareness and response to stimuli, or are in a vegetative state (VS) also known as unresponsive wakefulness syndrome, where there is neither, and the chance of recovery is much lower. But up to 40% of patients are misdiagnosed using these examinations.


"In patients with substantial cerebral oedema [swelling of the brain], prediction of outcome on the basis of standard clinical examination and structural brain imaging is probably little better than flipping a coin," writes Jamie Sleigh from the University of Auckland, New Zealand, and Catherine Warnaby from the University of Oxford, UK.


The study evaluated whether two new fMRI methods, PET with the imaging agent fluorodeoxyglucose (FDG) and fMRI during mental imagery tasks, could differentiate between vegetative and MCS in 126 patients with severe brain injury (81 in a MCS, 41 in a VS, and four with locked-in syndrome, a behaviorally unresponsive but conscious control group) referred to the University Hospital ofLiége, in Belgium, from across Europe.


The researchers then juxtaposed their results with the well-established standardized Coma Recovery Scale-Revised (CSR-R)behavioral test, considered the most authenticated and sensitive method for discerning very low awareness levels.


Overall, FDG-PET was better than fMRI in distinguishing conscious from unconscious patients. Mental imagery fMRI was less sensitive at diagnosis of a MCS than FDG-PET (45% vs. 93%), and had less agreement with behavioral CRS-R scores than FDG-PET (63% vs. 85%). FDG-PET was about 74% accurate in predicting the extent of recovery within the next year, as opposed to 56% for fMRI.


Notably, a third of the 36 patients diagnosed as behaviorallyunresponsive on the CSR-R test who were scanned with FDG-PETdemonstrated brain activity consistent with the presence of some consciousness. Nine patients of this cohort later recovered a reasonable level of consciousness.


"We confirm that a small but substantial proportion of behaviorallyunresponsive patients retain brain activity compatible with awareness. 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,” saidLaureys.


The authors note that the study was conducted in a specialist unitconcentrating on the diagnostic neuroimaging of disorders of consciousness and therefore roll out might be more challenging in less specialist units.


"From these data, it would be hard to sustain a confident diagnosis of unresponsive wakefulness syndrome solely on behavioral grounds, without PET imaging for confirmation. This work 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 practice without it,” commented Sleigh and Warnaby.

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