One in four unresponsive coma patients may retain some consciousness

At least 25% of unresponsive patients with impaired consciousness showed signs of brain activity, an estimate that is higher than previous studies had suggested.

“We found that at least one in four patients who were unresponsive to commands were actually quite focused and likely had high cognitive ability,” said Nicholas D. Schiff, MD, PhD, of the Feil Family Brain & Mind Institute and Department of Neurology, Rockefeller University Hospital and Weill Cornell Medicine in New York. Medscape Medical News.

“In other words, if you go to the bedside of a severely brain-injured patient and, upon careful examination, find no signs of response, no one can quantify in advance the likelihood that you will be wrong in thinking that this person is actually unconscious, unable to process language, and unable to perform advanced cognitive tasks. And the answer is currently at least one in four.”

The study results were published online July 14. New England Journal of Medicine.

What are the clinical implications?

Cognitive motor dissociation (CMD) is a condition in which severely brain-injured patients who do not respond to bedside instructions can show brain activity on functional MRI (fMRI) or electroencephalography (EEG) when presented with selective motor imagery instructions such as “imagine you are playing tennis” or “imagine opening and closing your hand.”

Previous studies have shown that CMD occurs in 10% to 20% of people with impaired consciousness, a rate similar to that of patients with acute or chronic brain injury.

Knowing that seemingly unconscious patients can show signs of cognitive processing could change the way clinicians and families interact with such patients: Aware but unresponsive patients may eventually be able to take advantage of new communication technologies such as brain-computer interfaces.

What's more, knowing an individual's CMD status may help predict prognosis: “One study found that patients with cognitive motor dissociation are four times more likely to be functionally independent within a year,” Schiff said.

Whereas most previous CMD studies have been conducted at a single centre and included relatively small cohorts, this new study was conducted across six multinational centres and included 353 adults with impaired consciousness (mean age 37.9 years, 64% male).

Participants were recruited in a variety of ways, including consecutive enrollment of critically ill patients in the intensive care unit and enrollment of patients with chronic illness or trauma following the acute phase of brain injury.

Responding to commands

Study participants were in different stages of recovery from acute brain injuries that occurred an average of eight months before the study began.

To determine whether participants had a visible response to instructions, trained staff used the Coma Recovery Scale–Revised (CRS-R), a tool whose scores range from 0 to 23, with higher scores indicating better neurobehavioral functioning.

Approximately 40% of patients were diagnosed with a coma or vegetative state, 29% with a minimally conscious state minus, and 22% with a minimally conscious state plus. Overall, 10% recovered from a minimally conscious state.

The researchers used fMRI or EEG to assess responses to timed and repeated commands in participants with no observable response to verbal commands and in participants with observable responses to verbal commands, including participants with a behavioral diagnosis of coma, vegetative state, or minimally conscious state minus.

Of the 353 study participants, 61% underwent at least one fMRI assessment and 74% underwent at least one EEG assessment. Both fMRI and EEG were performed in 35% of participants.

Schiff explained that the two types of assessments provide slightly different information because they measure different types of brain signals, and noted that while “every medical center in the world” has an EEG, many don't have fMRIs..

Brain imaging assessment captured brain activity in the motor areas of the frontal cortex when participants were given a task of visualizing a movement.

Of the 241 participants who were determined to be in a coma, vegetative state, or less than a minimally conscious state based on CRS-R scores, 60 (25%) responded to commands for task-based fMRI, task-based EEG, or both.

The percentage of participants with CMD varies from 2% to 45% depending on the study site, but Schiff said it's unclear why.

If all participants had been evaluated with both imaging techniques, the proportion of participants with CMD may have been even higher, he said.

Higher recognition rate than previous surveys

The researchers noted that the proportion of participants with CMD in their study was up to 10 percentage points higher than in previous studies, which they said may be due to the multimodal approach in which participants who were assessed with both fMRI and EEG were classified based on their response to either technique.

The mean age of patients with CMD was lower than that of patients without CMD (30.5 vs. 45.3 years).

Compared with participants without CMD, those with such dissociations were more likely to have brain trauma as an etiology (65% vs. 38%) and were more likely to be diagnosed with a minimally conscious state-negative on the CRS-R (53% vs. 38%).

Of the CMD patients, 18% were assessed with fMRI only, 22% with EEG only, and 60% with both fMRI and EEG.

Schiff noted that using both fMRI and EEG appears to be more sensitive in detecting brain activity during tasks than using either technique alone.

Of 112 participants diagnosed with or who had recovered from a minimally conscious state plus, 38% responded to commands with task-based fMRI, task-based EEG, or both. Of these participants, 23% were assessed with fMRI only, 19% with EEG only, and 58% with both fMRI and EEG.

“It's clear that research shows that patients who have sustained severe brain injuries continue to recover over time,” Schiff noted. “Every month, every week matters, and many of these patients will likely be on the road to recovery. And the later we measure, the more likely we are to find patients with CMD.”

These new results should prompt further research to explore whether detection of CMDs could lead to improved outcomes, the researchers noted: “Furthermore, standardization, validation, and simplification of task-based fMRI and EEG methods used to detect cognitive-motor dissociation are necessary to facilitate widespread clinical integration of these techniques as well as exploration of the bioethical implications of the findings.”

All study participants with chronic brain injury survived their initial illness or injury and had access to research facilities with advanced fMRI and EEG capabilities. “This survival bias may reflect participants' increased cognitive reserve and resilience over time; therefore, our findings may not be generalizable to the entire population of patients with cognitive-motor dissociation,” the researchers write.

Another study limitation is that the participating centers used heterogeneous strategies for data acquisition, analysis, and interpretation, resulting in differences in the number, type, and sequence of cognitive tasks assessed with fMRI and EEG.

“These differences, together with differences in recruitment strategies and participant characteristics, may contribute to the uneven proportion of participants with cognitive-motor dissociation observed at each center; therefore, our findings may not be generalizable to all centers,” the researchers wrote.

Only a few academic medical centers have the specially trained personnel and technology required to evaluate patients with CMD, and the researchers noted that this limits the feasibility of carrying out these evaluations in general practice.

Challenging Research

Leave a Comment Medscape Medical NewsAarti Sarwar, MD, The professor of neurology and chief of the neurocritical care division at Virginia Commonwealth University in Richmond, Virginia, noted that this was an “extremely challenging” study to conduct, given that only a few academic centers are equipped to perform both fMRI and quantitative EEG analysis.

“Typically, finding patients this far away who are able and cared for enough to undergo clinical, radiological and electrophysiological testing is a huge task in itself.”

Sarwal said the study Coma Treatment Campaign is a clinical, scientific and public health initiative by the Neurocritical Care Society that addresses the concept of coma as a treatable medical entity.

“This study continues to highlight the challenges of predicting outcomes in patients with acute brain injury by demonstrating greater cognitive function than previously thought,” she said.

Sarwar believes the study's biggest impact is that it highlights the need for further research to understand the extent and quality of cognitive processing in patients with disorders of consciousness, but also the need for a “healthy debate” about the cost-benefit analysis of pursuing such research, given the limited number of patients with access to resources.

“This discussion needs to include caregivers and family members who are outside the traditional stakeholders who oversee the science.”

While communicating with comatose patients is still “a long way off,” Sarwal said the study is “a step in the right direction.”

The research was funded by the James S. McDonnell Foundation and others. Schiff and Sarwal report no relevant financial disclosures.