A widely available technique that measures electrical activity in the brain may provide a more accurate means of characterizing the extent of consciousness in brain-injured patients, Weill Cornell Medical College researchers report. If it is broadly adopted for this purpose, the technology, electroencephalography (EEG), could help detect increased awareness in potentially thousands of patients previously classified as unresponsive to the world around them.
Assessing cognitive function in severely brain-injured patients with limited signs of consciousness is challenging for clinicians, as the traditional diagnostic tools often produce unreliable results. In a study published in the Annals of Neurology in October, the investigators demonstrate that the EEG, otherwise mainly used as a diagnostic test for epilepsy, captured potential preservation of cognitive functions in patients that was typically imperceptible at their bedsides or through other imaging techniques. EEG is easily repeatable across medical centers, has no side effects and doesn’t require a patient’s active participation.
"EEGs allow for a reliable, repeatable and accurate diagnosis," said senior author Dr. Nicholas Schiff, the Jerold B. Katz Professor of Neurology and Neuroscience at the Feil Family Brain and Mind Research Institute and a professor of medical ethics in medicine. "If someone looks awake on an EEG but is determined at the bedside to be in a vegetative state, we can show the evidence for the risk that some harbor high levels of cognition. EEGs provide an operational step forward and also help to frame and assign a risk that someone may be misdiagnosed."
The findings underscore the complexity of distinguishing disorders of consciousness from one another. Because the differences are subtle to discern, patients can be misdiagnosed and fail to receive the most appropriate treatment.
The differences between the conditions are significant. Patients who are comatose can’t be aroused; those who are in a vegetative state intermittently open their eyes but don’t respond to external stimuli; and patients who are in a minimally conscious state show intermittent, inconsistent responses to the world.
Clinicians seeking to characterize the awareness of these patients need to determine their brain activity. That has historically meant observing a patient’s physical cues and responses to stimuli. But motor function can oftentimes be undetectable, increasing the risk of misclassification.
"The main problem with bedside examination is that it heavily relies on movement," said first author Dr. Peter Forgacs, an instructor in neurology at Weill Cornell and an instructor of clinical investigation at The Rockefeller University. "If you imagine you cannot move at all, even your eyes, there is no way just at the bedside to assess how much preserved function there is."
Researchers have previously eyed functional magnetic resonance imaging (fMRI) to compensate for these shortcomings. But the procedure, which gauges brain activity through the measurement of blood flow fluctuations, can be problematic since the test requires a patient’s active responses to commands. In fact, the results of fMRI have often been inconsistent with those of behavioral assessments, the authors write.
EEG, however, doesn’t use voluntary factors to determine brain activity. For that reason, it could be used as a broad screening tool — a test to accompany bedside analyses — and direct some patients to fMRI and more specialized behavioral evaluations to ensure a more accurate diagnosis.
"EEG is an indirect method, independent of movement because it measures brain activity directly," Dr. Forgacs said. "It measures the electrical activity the brain is producing, so if somebody has an overwhelming injury to their motor system, but their brain is relatively intact, that’s a patient whom EEG can help."
For their study, the investigators conducted bedside assessments and administered days-long EEGs for 44 patients with severe brain injuries caused by trauma, oxygen deprivation, stroke or brain hemorrhage. In addition to EEG and bedside assessments, 26 of the 44 patients underwent fMRIs to determine if they could follow investigators’ commands to, say, visualize a tennis match. Researchers also correlated EEG with brain energy metabolism using positron emission tomography, or PET scans.
Using EEGs, the team looked for organized brain patterns during wake and sleep cycles. During sleep, the researchers looked for specific burst patterns of activity that require functional connection in regions important to preservation of consciousness. Researchers determined that many of the patients with limited observable cognitive functions maintained normal or near-normal brain rhythms during wakefulness and sleep, underscoring the potential that they had some consciousness.
The team found that in some instances, EEG outcomes correlated with neuroimaging findings that unequivocally contradicted diagnoses yielded from bedside characterizations. In four patients who appeared in vegetative or minimally conscious states who showed preserved cognitive abilities during fMRI studies, the EEG outcomes demonstrated preservation of normal wake and sleep patterns, reinforcing the use of EEG to clarify results from other diagnostic techniques.
"Those patients who have evidence of reliable command only in the fMRI scanner, but not at the bedside, many times are called vegetative or minimally conscious when they shouldn’t be," Dr. Forgacs said. "Doing an EEG for overnight or even for a couple of hours can be an assessment on the possibility or chances that there may be a higher connection not present at the bedside."