Summary: Researchers detected brain waves indicative of ‘hidden’ consciousness in 15% of patients with TBI four days after the injury occurred. Among those patients, 50% improved and were able to follow verbal commands before being discharged from hospital compared to just 26% who did not show signs of hidden consciousness.
Source: Columbia University
Close analysis of EEG data reveals that nearly 1 in 7 brain-injured ICU patients shows evidence of hidden consciousness just days after injury. Patients with such signs are more likely to recover, neurologists at Columbia University and NewYork-Presbyterian have found.
In the study, the researchers used a machine learning technique to analyze standard EEG data collected from 104 unresponsive patients to look for patient-specific brain activity indicating that they could understand instructions to move their hands. If the findings are confirmed in larger studies, the technique could help physicians better predict which patients will likely regain consciousness.
“Though our study was small, it suggests that EEG—a tool that’s readily available at the patient’s bedside in the ICU in almost any hospital across the globe—has the potential to completely change how we manage patients with acute brain injury,” says Jan Claassen, MD, PhD, associate professor of neurology at Columbia University Vagelos College of Physicians and Surgeons, lead author of the study, and director of the Neurological Intensive Care Unit at NewYork-Presbyterian/Columbia University Irving Medical Center.
The findings were published today in the New England Journal of Medicine.
Why It’s Important
Currently, there’s no perfect way to accurately predict the chance of recovery for unconscious, brain-injured patients.
Electroencephalography (EEG) is commonly used in intensive care to monitor critically ill patients at risk for seizures and may be a relatively easy and fast way to identify signs of hidden consciousness in unresponsive patients who have recently experienced a brain injury.
Difficult discussions between families and health care providers determine the intensity of medical support for unresponsive patients. The decision to withdraw life-sustaining therapies from patients who appear to have little chance to recover are frequently made within the first weeks following brain injury.
Clinicians use bedside neurological examinations, imaging and electrophysiological studies, and laboratory values to estimate the likelihood of recovery for people who are unresponsive in the days and weeks after sustaining a brain injury. However, these predictions are frequently inaccurate.
Increasingly, however, studies suggest that some unresponsive patients may have hidden cognitive abilities and that delayed recovery is more common than previously thought.
Hidden consciousness was first identified over a decade ago using MRI in a brain-injured patient who had been unresponsive for years. Since then, studies using MRI or EEG have detected signs of hidden consciousness in 14% of chronically unresponsive patients. But MRI is challenging to perform in a critical care setting.
“One of the most challenging problems in the ICU involves predicting recovery, and not just survival, for patients who are unconscious after a brain injury,” says Claassen. “Since the first studies describing hidden consciousness, we’ve been looking for a practical way to do this in the early days after brain injury, when treatment decisions that affect outcomes are often made.”
What the Researchers Did
Claassen and his team studied 104 adult patients in an intensive care unit who had recently sustained a sudden brain injury due to hemorrhage, trauma, or oxygen deprivation. Though none of the patients was paralyzed, they were unable to talk and did not respond to commands to move (e.g., make a fist or wiggle their toes).
Every day, in addition to standard neurological exams, the patients were asked multiple times to open and close their hands or stop opening and closing their hands. A complex algorithm was used to analyze EEG data from these sessions to look for signs that a patient detected a difference between the commands. A reproducibly different pattern of activity between the commands suggested that a patient was able to understand the command but could not perform the movement.
The researchers followed up with patients who were discharged from the hospital a year later.
What the Study Found
Within four days of the injury, 15% of the still-unresponsive patients had brain activity patterns on at least one EEG recording, suggesting hidden consciousness. Among the patients with these patterns, 50% improved and were able to follow verbal commands before being discharged from the hospital versus 26% of those without such brain activity.
A year later, 44% of patients with brain activity patterns were able to function independently for up to eight hours each day, compared with only 14% of those without such signals. Approximately one-third of patients in each group—those with early EEG evidence of hidden consciousness and those without—died.
Hidden consciousness signals were also more common in patients with brain injuries from hemorrhage and trauma than from oxygen deprivation. However, the study lacked sufficient statistical power to determine the predictive value of EEG analysis across different causes of brain injury.
“This study shows that some patients who are unresponsive for days or longer may have cognitive processing capabilities sufficient to distinguish commands, and those patients have a higher chance of recovering,” says Claassen.
Bigger studies—especially in patients with a single cause of brain injury—are needed to determine the utility of EEG monitoring in predicting patient outcomes.
There are some technical challenges with EEG monitoring: Neurological exams must be performed at least once or twice a day as consciousness fluctuates after a brain injury; spoken commands must be highly synchronized with EEG recordings; and additional computers are needed to do the analysis.
“It’s important to begin monitoring with EEG as early as possible and to assess at several time points as recovery after a severe brain injury is a complex process,” Claassen says.
Most importantly, he says, these assessments have to be designed meticulously because artifacts may be misinterpreted as brain activation if the testing paradigm is poorly designed or the computational analysis is applied incorrectly.
Funding: The study was supported by the Dana Foundation and the James S. McDonnell Foundation.
Dr. Rohaut received postdoctoral grants from Amicale des Anciens Internes des Hôpitaux de Paris and Syndicat des Chefs de Cliniques et Assistants des Hôpitaux de Paris, Assistance Publique–Hôpitaux de Paris, and the Philippe Foundation.
The authors report no relevant financial or other conflicts of interest.
Additional authors are Kevin Doyle (Columbia University Irving Medical Center and NewYork-Presbyterian), Adu Matory (CUIMC-NYP), Caroline Couch (CUIMC-NYP), Kelly Burger (CUIMC-NYP), Angela Velazquez (CUIMC-NYP), Joshua Okonkwo (CUIMC-NYP), Jean-Remi King (New York University), Soojin Park (CUIMC-NYP), Sachin Agarwal (CUIMC-NYP), David Roh (CUIMC-NYP), Murad Megjhani (CUIMC-NYP), Andrew Eliseyev (CUIMC-NYP), E. Sander Connolly (CUIMC-NYP), and Benjamin Rohaut (CUIMC-NYP).
Jan Claassen – Columbia University
The image is in the public domain.
Original Research: Closed access
“Detection of Brain Activation in Unresponsive Patients with Acute Brain Injury”. Jan Claassen, M.D., Kevin Doyle, M.A., Adu Matory, B.A., Caroline Couch, B.A., Kelly M. Burger, B.A., R.E.E.G.T., Angela Velazquez, M.D., Joshua U. Okonkwo, M.D., Jean-Rémi King, Ph.D., Soojin Park, M.D., Sachin Agarwal, M.D., David Roh, M.D., Murad Megjhani, Ph.D., Andrey Eliseyev, Ph.D., E. Sander Connolly, M.D., and Benjamin Rohaut, M.D..
New England Journal of Medicine. doi:10.1056/NEJMoa1812757
Detection of Brain Activation in Unresponsive Patients with Acute Brain Injury
Brain activation in response to spoken motor commands can be detected by electroencephalography (EEG) in clinically unresponsive patients. The prevalence and prognostic importance of a dissociation between commanded motor behavior and brain activation in the first few days after brain injury are not well understood.
We studied a prospective, consecutive series of patients in a single intensive care unit who had acute brain injury from a variety of causes and who were unresponsive to spoken commands, including some patients with the ability to localize painful stimuli or to fixate on or track visual stimuli. Machine learning was applied to EEG recordings to detect brain activation in response to commands that patients move their hands. The functional outcome at 12 months was determined with the Glasgow Outcome Scale–Extended (GOS-E; levels range from 1 to 8, with higher levels indicating better outcomes).
A total of 16 of 104 unresponsive patients (15%) had brain activation detected by EEG at a median of 4 days after injury. The condition in 8 of these 16 patients (50%) and in 23 of 88 patients (26%) without brain activation improved such that they were able to follow commands before discharge. At 12 months, 7 of 16 patients (44%) with brain activation and 12 of 84 patients (14%) without brain activation had a GOS-E level of 4 or higher, denoting the ability to function independently for 8 hours (odds ratio, 4.6; 95% confidence interval, 1.2 to 17.1).
A dissociation between the absence of behavioral responses to motor commands and the evidence of brain activation in response to these commands in EEG recordings was found in 15% of patients in a consecutive series of patients with acute brain injury. (Supported by the Dana Foundation and the James S. McDonnell Foundation.)