Advanced tools offer improved insights into brain injury patients’ condition and their potential for recovery

Trauma centers nationwide will begin to test a new approach for assessing traumatic brain injury (TBI) that is expected to lead to more accurate diagnoses and more appropriate treatment and follow-up for patients.

The new framework, which was developed by a coalition of experts and patients from 14 countries and spearheaded by the National Institutes of Health, expands the assessment beyond immediate clinical symptoms. Added criteria would include biomarkers, CT and MRI scans, and factors, such as other medical conditions and how the trauma occurred.

The framework appears in Lancet Neurology.

For 51 years, trauma centers have used the Glasgow Coma Scale to assess patients with TBI, roughly dividing them into mild, moderate and severe categories, based solely on their level of consciousness and a handful of other clinical symptoms.

That diagnosis determined the level of care patients received in the emergency department and afterward. For severe cases, it also influenced the guidance doctors gave the patients’ families, including recommendations around removal of life support. Yet, doctors have long understood that those tests did not tell the whole story.

“There are patients diagnosed with concussion whose symptoms are dismissed and receive no follow-up because it’s ‘only’ concussion, and they go on to live with debilitating symptoms that destroy their quality of life,” said corresponding author Geoffrey Manley, MD, Ph.D., professor of neurosurgery at UC San Francisco and a member of the UCSF Weill Institute for Neurosciences.

“On the other hand, there are patients that were diagnosed with ‘severe’ TBI, leading full lives, whose families had to consider removing life-sustaining treatment.”

In the United States, TBI resulted in approximately 70,000 deaths in 2021 and accounts for about half-a-million permanent disabilities each year. Motor vehicle accidents, falls, and assault are the most common causes.

New system will better match patients to treatments

Known as CBI-M, the framework comprises four pillars—clinical, biomarker, imaging, and modifiers—that were developed by working groups of federal partners, TBI experts, scientists, and patients.

“The proposed framework marks a major step forward,” said co-senior author Michael McCrea, Ph.D., professor of neurosurgery and co-director of the Center for Neurotrauma Research at the Medical College of Wisconsin in Milwaukee.

“We will be much better equipped to match patients to treatments that give them the best chance of survival, recovery, and return to normal life function.”

The framework was led by the NIH National Institute of Neurological Disorders and Stroke (NIH-NINDS), for which Manley, McCrea, and their co-first and co-senior authors are members of the steering committee on improving TBI characterization.

The clinical pillar retains the Glasgow Coma Scale’s total score as a central element of the assessment, measuring consciousness along with pupil reactivity as an indication of brain function. 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.

“This pillar should be assessed as first priority in all patients,” said co-senior author Andrew Maas, MD, Ph.D., emeritus professor of neurosurgery at the Antwerp University Hospital and University of Antwerp, Belgium.

“Research has shown that the elements of this pillar are highly predictive of injury severity and patient outcome.”

Biomarkers, imaging, modifiers offer critical clues to recovery

The second pillar uses biomarkers identified in blood tests to provide objective indicators of tissue damage, overcoming the limitations of clinical assessment that may inadvertently include symptoms unrelated to TBI.

Significantly, low levels of these biomarkers determine which patients do not require CT scans, reducing unnecessary radiation exposure and health care costs. These patients can then be discharged. In those with more severe injuries, CT and MRI imaging—the framework’s third pillar—are important in identifying blood clots, bleeding, and lesions that point to present and future symptoms.

The biomarkers also identify the appropriate patients to enroll in clinical trials to develop new TBI medications, which have not advanced in the last 30 years. A recently launched trial that will roll out in 18 trauma sites nationwide may finally give rise to new treatments.

“These biomarkers are crucial in clinical trials,” Manley said. “In the past, we couldn’t tell the difference between a knock on the head and a TBI. Thanks to biomarkers, we can make this distinction and ensure that it’s the TBI patient who enrolls in the trial.”

The final pillar, modifiers, assesses how the injury occurred, such as a fall, blow or sharp object penetration. It also includes existing conditions and medications, health care access, prior TBIs, substance abuse, and living circumstances.

“This pillar summarizes the factors that research tells us need to be considered when we interpret a patient’s clinical, blood biomarker, and neuroimaging exams,” said co-first author Kristen Dams-O’Connor, Ph.D., professor of rehabilitation and human performance, and neurology, and director of the Brain Injury Research Center at the Icahn School of Medicine at Mount Sinai in New York.

“One example is a patient with underlying cognitive impairment who may require acute monitoring for risk of clinical deterioration, regardless of findings on the initial clinical exam,” she said.

The proposed framework is being phased in at trauma centers on a trial basis. It will be refined and validated before it is fully implemented.