Better Care, Better Outcomes: New TBI Characterization System Aims to Improve Diagnoses and Treatment

The medical community has taken another step toward implementing a new, more robust traumatic brain injury (TBI) characterization system.

In May, a coalition of experts from 14 countries proposed a new way to evaluate TBI patients that is expected to lead to more accurate diagnoses and more appropriate treatment plans. The proposed TBI characterization system, referred to as the CBI-M framework and published in Lancet Neurology, expands the assessment beyond a patient’s immediate clinical symptoms. In addition to assessing clinical symptoms (the C in CBI-M), new assessment criteria include blood-based biomarkers (B), imaging such as CT and MRI scans (I), and modifiers (M) – factors such as a patient’s age, sex, preexisting medical conditions, and environmental influences.

“This new approach to characterizing traumatic brain injury will advance our ability to understand the initial injury,” said John D. Corrigan, PhD, National Research Director for the Brain Injury Association of America and professor in the Department of Physical Medicine and Rehabilitation at The Ohio State University. “People who have had a traumatic brain injury will welcome our abandonment of the overly simplistic ‘mild, moderate, severe’ because for many that nomenclature mischaracterized the lived experience of these injuries.”

For more than 50 years, trauma centers have used the Glasgow Coma Scale (GCS) to assess and categorize TBI patients as having sustained a mild, moderate, or severe TBI. While the GCS remains an important tool for assessing brain injury patients, the classification of patients based solely on the patient’s GCS score has been criticized as outdated, inaccurate, and ineffective.

In 2022, the National Academies of Sciences, Engineering, and Medicine published a report calling for the creation and implementation of an updated classification system for TBI. The report cited the need for a more nuanced, personalized, and evidence-guided taxonomy for TBI that uses clinical and biological markers to support more effective assessment, treatment, prognosis, and rehabilitation.

Geoffrey Manley, MD, PhD, Chief of Neurosurgery at Zuckerberg San Francisco General Hospital and Professor and Vice Chairman of Neurological Surgery at the University of California, San Francisco (UCSF), and a lead author of the Lancet Neurology report, pointed out that other disease states, such as cancer, are not classified or categorized using similarly crude framework, and decades ago created a framework similar to CBI-M – the TNM Staging System, which describes the size of the tumor and any spread of cancer into nearby tissue; spread of cancer to nearby lymph nodes; and metastasis, or the spread of cancer to other parts of the body – that is still utilized to this day.

“Who would ever develop a drug or treatment for ‘severe’ cancer? And yet here we are, trying to develop drugs and treatment for ‘severe’ TBI,” he said. “Would we be where we are with cancer treatment today if we had not taken a more rigorous and detailed approach to describing these patients? I think the answer to that is, if we were still out there saying everyone had mild, moderate, or severe cancer, I’m 99.9 percent sure we wouldn’t have the treatments we have today.”

Dr. Manley said the crude categorization of TBI patients has been a problem for years, and is often not reflective of a patient’s long-term recovery.

“We began hearing from patients. They were saying, ‘Somebody told me I had a mild TBI, but I can’t work anymore, I’m tired all the time but I can’t sleep, my cognition isn’t very good,’” he said. He pointed to the TRACK-TBI research initiative and CENTERTBI, two large observational studies conducted in the U.S. and Europe, respectively, which both found that nearly half of patients diagnosed with mild TBI had not fully recovered after one year. “There’s a disconnect there,” he noted.

That disconnect is not limited to mild TBI patients who experience chronic symptoms. “Today, ‘severe’ is often misinterpreted as a death sentence,” Dr. Manley explained, pointing out that approximately half of people who die from severe TBI die because someone withdrew life support. However, a study published in JAMA Neurology found that one in five people who were diagnosed with a severe TBI had recovered to their pre-injury function after 12 months.

By developing a new characterization system for TBI patients, the hope is to create a framework to describe patients that does not create terms of bias. And, Dr. Manley added, “I think that mild, moderate, and severe are terms that are fraught with bias for individual patients.”

The CBI-M Pillars

CBI-M consists of four pillars: clinical, biomarker, imaging, and modifiers.

Clinical: The clinical pillar retains the GCS score – which evaluates a person’s level of consciousness along with pupil reactivity – as a central element of the assessment. The framework recommends including the scale’s responses to eye, verbal, and motor commands or stimuli, presence of amnesia, and symptoms like headache, dizziness, and noise sensitivity.

Biomarker: The biomarker pillar uses biomarkers identified in blood tests to provide objective indicators of tissue damage. Low levels of these biomarkers determine which patients don’t require CT scans, helping to reduce unnecessary radiation exposure and health care costs. Biomarkers can also identify patients to enroll in clinical trials to develop new medications for TBI.

Imaging: CT and MRI imaging are important in identifying blood clots, bleeding, and lesions, particularly in patients with more severe injuries, that can point to present and future symptoms.

Modifiers: While the C, B, and I pillars look at what a brain injury does to a patient, the modifiers pillar looks at what the patient brings to the injury. This can include things like age, sex, and preexisting conditions, such as medications a person is taking, their health care access, history of prior TBI, substance abuse, or mental health issues.

“With the four pillars, we hope for a better characterization, which will then lead to improved understanding of the disease in a particular patient or group of patients, and allows for more targeted interventions,” said Andrew Maas, MD, PhD, emeritus professor of neurosurgery at Antwerp University Hospital in Belgium and co-author of the Lancet Neurology report.

Dr. Maas noted that the idea is not to follow a rigid sequence – that is, collecting clinical data, then biomarker data, then imaging, then looking at modifiers. “It can be mixed up. Or if someone’s condition mandates a quick CT, that takes preference, by definition,” he explained. “For instance, biomarkers do have an added value in the sense of a patient’s prognosis, but does it mean you need to do it? No. But it gives you insight. Which of the pillars or various components will be the most relevant? We don’t know yet. There’s more work to be done.”

Dr. Manley provided an example of how collecting information based on the pillars would help him determine a treatment plan: “By using CBI-M, rather than talking about a patient with mild TBI, I would be able to say, I have a patient a with GCS score of 14, a GFAP [glial fibrillary acidic protein, a biomarker that indicates damage to a specific brain cell] of 1,000, and frontal lobe contusions. Here’s the way this patient should be treated. And that treatment may be modified based upon their modifiers.”

Using this more detailed framework, Dr. Manley believes, will allow for better patient care and, ultimately, better outcomes.

An Ongoing Process

People have had a lot of questions about what this new framework means.

Dr. Corrigan noted that while there is a general consensus that the brain injury community needs to move past the language of “mild, moderate, severe,” there are questions about what language will be used moving forward. “We used to say mild TBI, now what do we say? Is ‘concussion’ now going to be used where we used to say ‘mTBI’? There’s some trepidation as the field is trying to decide how it’s going to talk,” he said. That, I see as something that is imminently addressable.”

Dr. Manley pointed out that the work is far from finished, and that CBI-M is not meant to be a finished product at this point.

“This is the first iteration,” he explained. “This is meant to be the first step in the evolution of a better characterization of TBI. To try to have better treatment.”

Further building out this system will require thinking about pathways of care based on the CBI-M framework, Dr. Manley explained. “For example, when you come into an acute care setting, how are we assessing your clinical pillar? How are we using the blood-based biomarkers? How are we implementing the imaging content? How are we starting to collect modifiers?”

He acknowledged this will be a big hurdle – particularly collecting a patient’s modifiers. While many medical facilities are already assessing a patient’s GCS or collecting imaging like CTs, modifiers are rarely collected – especially in a busy emergency room.

“Now, we’re not going to ask an ER physician to collect 40 modifiers,” he said, adding that research can help determine which modifiers are the most important to collect. “There’s the understanding that, if we collect the top five, we’re going to miss the other 35, but if we at least collect those top five, that will be better than what we’re doing today, which is often none.”

There is also a need to develop better systems of follow-up care, Dr. Manley said, explaining that most TBI patients do not receive any follow-up care. “They might go to acute rehab for a week or two if they’re lucky, and then after that, who takes care of them? We’ve got a lot of things to create and build and develop in order to do a better job with this, but every journey starts with a first step, and I think that this is the first step to rethinking things, and getting out of this rut that we’ve been in for the last 20 to 30 years.”

Using Research to Move Forward

Dr. Maas said conducting a retrospective analysis of existing datasets, such as TRACK-TBI and CENTER-TBI, to see how well the CBI-M model performs, as well as identifying associations between the pillars, will be an important next step. “This will provide an evidence base on which the concept can be refined,” he explained.

Collectively, TRACK-TBI and CENTER-TBI have detailed, granular data on more than 6,000 patients of all severities. “Most of the elements of the pillars were collected in those data sets,” Dr. Maas noted. “We have a unique opportunity to look at how those elements are associated with clinical decision making, how they can be combined, associated with outcome, and put that into models to classify patients and predict outcomes.”

In addition to exploring the CBI-M framework through retrospective data analysis, Dr. Maas believes the new framework can help existing TBI survivors retrospectively, particularly those whose initial categorization does not reflect their long-term journey.

“It’s not only researchers and clinicians who say we need to move toward a more detailed characterization – it’s the patients themselves,” he explained. “In a patient who is seen in the ER with a ‘mild’ injury, is sent home, and is not able to return to work because of a number of issues – he was given a stamp of ‘mild’ at the moment he left the ER. He never gets rid of that stamp. So during the course of this disease, doctors, friends, lawyers – they don’t take him seriously. And that’s a major obstacle to the recovery of such patients.”

Conversely, this label can be harmful to patients who are diagnosed as having a severe TBI yet make an excellent recovery. “People will always look at him or her and say, ‘You had a severe brain injury, are you sure you can do this?’ If they apply for a new job, will they be accepted or will they be turned down? This stamp of severe TBI totally disregards the situation of the patient at the time. The stamp given at the hospital remains with them for rest of their lives, and indeed impacts the rest of their lives, mostly in a negative way,” Dr. Maas said.