Some brain injury patients may appear to be in a coma but are not, suggest scientists, who said a routine clinical care technique could help identify those with cognitive motor dissociation or “hidden consciousness”, improving survival and recovery odds.
These patients may be processing at least some of what is happening around them but cannot physically respond – and without a physical response, a physician might assume a patient hasn’t understood, said Sudhin Shah, a neuroscientist at Weill Cornell Medicine in New York City.
“Unfortunately, it could be that you are processing, you are understanding, you are wanting to talk to me. You just can’t.”
This break between understanding and responding is called cognitive motor dissociation (CMD), a disorder of consciousness after brain injury.
About 15% of patients believed to be unresponsive are predicted to be experiencing CMD, but most do not get a diagnosis because that requires both advanced equipment and training, reports The Washington Post.
Now, researchers have used structural magnetic resonance imaging (MRI) – a technique that is already part of routine clinical care – to identify brain lesion patterns specific to patients with CMD.
These MRI scans could be used as a screening tool to identify patients likely to have CMD, improving their chance of not being removed from life support too soon and recovering.
CMD diagnosis possible only in a few labs
Today, if someone arrives at an emergency room with a brain injury, medical staff will often use CT scans or structural MRI – which generates pictures of the person’s brain – to identify issues, including swelling, fluid leaks or haemorrhaging, that need to be dealt with immediately.
An EEG will often also be performed to look for electrical activity, a good indicator of overall brain health.
Depending on the results of those tests, patients will be given medication, to prevent seizures for example, and will possibly be placed on life support.
“Right now, diagnosis for CMD requires access to a handful of labs around the world,” said Shah, who was not involved in the study.
To diagnose CMD, there are two main options: functional EEG, a far more advanced approach than traditional EEG, and functional magnetic resonance imaging (fMRI), which measures changes in blood flow throughout the brain.
Over the course of about 30 minutes, the patients are repeatedly asked to respond to carefully chosen questions or commands, for instance, “Open and close your hand,” and “Imagine opening and closing your hand.”
Scientists and physicians need extensive training to analyse and interpret the patients’ brain activity data collected during questioning.
Making CMD diagnosis accessible
Jan Claassen, a neurocritical care physician and the director of Critical Care Neurology at Columbia University/New York-Presbyterian Hospital, and whose laboratory led the recent study, was determined to make CMD diagnosis simpler by incorporating equipment already available in most hospitals.
He and his colleagues turned to structural MRI to look for brain lesions – a classic approach to understanding brain function – in patients with CMD, Claassen said.
But before bringing structural MRI data into the equation, they used the current functional EEG approach to confidently identify 21 CMD patients within a group of 107 brain injury patients. Then they compared EEG and structural MRI data among and between the two groups and were able to identify two patterns of brain lesions only seen in CMD patients.
Those lesion patterns were, not surprisingly, in areas of the brain important for motor output but not in regions important for command comprehension or arousal, indicating that patients with CMD would be able to process information but be unable to physically respond.
Replicating and refining these results in a larger group of patients is essential, Claassen said, but knowing which lesion patterns are more likely in patients with CMD could ultimately be used as a screening tool when someone enters a hospital with a brain injury.
Some of those patients are children.
Even less known about paediatric CMD
Aidan Galaska suffered a severe brain injury in a car accident, in 2013, at age nine. His older brother Cole died at the scene.
In the months after the accident, Aidan underwent a battery of tests, including those where he was asked to respond to questions.
“After a brief five-minute assessment, they would decide that he was in a persistent vegetative state,” said Laura Galaska, Aidan’s mother. But, Galaska said, she had a gut feeling that “Aidan was in there”.
On a few occasions, she had seen her son move or laugh in a way that she felt indicated he was aware of his surroundings, even if the doctors thought it was a random bodily reflex. “On paper, it looked very grim,” she admitted.
After years, Galaska found scientists and physicians who listened, and who would introduce her to Shah, in 2018.
Aidan was enrolled in studies, including one with Shah, to learn what might be happening in his brain. Finally, they received news: Aidan had CMD. He was the first child to receive that diagnosis.
“That's five years,” Shah said. “Five years of that family trying to find an answer to what should be a basic question: is my child hearing or understanding what I'm saying?”
And for Galaska, those five years of waiting were also filled with doctors who, she said, treated her son not just as if he were unconscious, but sub-human. “It is never appropriate to talk about a patient in front of him as if his future doesn’t matter, as if there is no hope,” Galaska said.
Claassen agreed, and said he tells every doctor he trains, “When you’re at the bedside, in the room of a patient who is apparently unresponsive, assume they are actually conscious. When you have a meeting with a family at the bedside, integrate the patient even though they can’t actually take part in the discussion.”
Aidan died last year of Covid-19 after a lung infection.
CMD diagnosis could be lifesaving, life-changing
A study last year, also led by Claassen, showed that patients with CMD have a higher chance of recovery than unresponsive patients without CMD, and so being able to identify patients with CMD would reduce the risk that life-sustaining therapies are withdrawn prematurely.
Knowing if a loved one has CMD will also allow families to make better decisions about care: for instance, whether they should put their resources toward a rehabilitation programme, said Jose Suarez, director of the Neurocritical Care Division at Johns Hopkins University.
For CMD patients, “we want to be aggressive and continue with care”, said Suarez, who was not involved in the study.
Knowing which patients have CMD could lead to CMD-specific clinical trials to evaluate the effectiveness of different brain stimulation techniques or therapeutics such as the drug amantadine, he added.
Amantadine has been shown to help with recovery in patients in a vegetative or minimally conscious state. “We could replicate the trial in CMD patients,” Suarez said, “and see whether those who received amantadine had a more accelerated pace of recovery.”
CMD patients may one day also be able to use technologies such as brain-computer interfaces (BCI), Claassen said, which take signals from a person’s brain and translate them into commands, allowing the person to control an external device.
Claassen and his colleagues are hoping to adapt a BCI for patients with CMD “to build a communication bridge”, he said.
“There are people potentially locked in for decades,” Shah said, “with none of their family and the rest of the world knowing what’s going on.”
Being able to more easily identify people with CMD is crucial, she said, but “that doesn’t mean anything if we don’t then go and try to get them out.”
Study details
Injury patterns associated with cognitive motor dissociation
Eva Franzova, Qi Shen, Jan Claassen, et al.
Published in Brain on 14 August 2023
Abstract
In unconscious appearing patients with acute brain injury, wilful brain activation to motor commands without behavioural signs of command following, known as cognitive motor dissociation (CMD), is associated with functional recovery. CMD can be detected by applying machine learning to EEG recorded during motor command presentation in behaviourally unresponsive patients. Identifying patients with CMD carries clinical implications for patient interactions, communication with families, and guidance of therapeutic decisions but underlying mechanisms of CMD remain unknown.
By analysing structural lesion patterns and network level dysfunction we tested the hypothesis that, in cases with preserved arousal and command comprehension, a failure to integrate comprehended motor commands with motor outputs underlies CMD. Manual segmentation of T2-fluid attenuated inversion recovery and diffusion weighted imaging sequences quantifying structural injury was performed in consecutive unresponsive patients with acute brain injury (n = 107) who underwent EEG-based CMD assessments and MRI. Lesion pattern analysis was applied to identify lesion patterns common among patients with (n = 21) and without CMD (n = 86).
Thalamocortical and cortico-cortical network connectivity were assessed applying ABCD classification of power spectral density plots and weighted pairwise phase consistency (WPPC) to resting EEG, respectively.
Two distinct structural lesion patterns were identified on MRI for CMD and three for non-CMD patients. In non-CMD patients, injury to brainstem arousal pathways including the midbrain were seen, while no CMD patients had midbrain lesions. A group of non-CMD patients was identified with injury to the left thalamus, implicating possible language comprehension difficulties. Shared lesion patterns of globus pallidus and putamen were seen for a group of CMD patients, which have been implicated as part of the anterior forebrain mesocircuit in patients with reversible disorders of consciousness. Thalamocortical network dysfunction was less common in CMD patients [ABCD-index 2.3 (interquartile range, IQR 2.1–3.0) versus 1.4 (IQR 1.0–2.0), P < 0.0001; presence of D 36% versus 3%, P = 0.0006], but WPPC was not different. Bilateral cortical lesions were seen in patients with and without CMD.
Thalamocortical disruption did not differ for those with CMD, but long-range WPPC was decreased in 1–4 Hz [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.7–0.9] and increased in 14–30 Hz frequency ranges (OR 1.2; 95% CI 1.0–1.5).
These structural and functional data implicate a failure of motor command integration at the anterior forebrain mesocircuit level with preserved thalamocortical network function for CMD patients with subcortical lesions. Amongst patients with bilateral cortical lesions preserved cortico-cortical network function is associated with CMD detection. These data may allow screening for CMD based on widely available structural MRI and resting EEG.
Brain article – Injury patterns associated with cognitive motor dissociation (Open access)
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