New System Combines Biomarkers, Imaging and Modifiers for Accurate TBI Diagnosis

In the United States, traumatic brain injury (TBI) led to around 70,000 fatalities in 2021 and contributes to about half a million cases of permanent disability each year. Common causes include motor vehicle accidents, falls, and assaults. For over 50 years, trauma centers have relied on the Glasgow Coma Scale (GCS) to assess TBI patients, categorizing them into mild, moderate, or severe based on their level of consciousness and other clinical symptoms. This diagnosis determined the level of care provided in the emergency department and afterward, and in severe cases, it influenced the decisions regarding life support withdrawal. However, doctors have long recognized that the GCS does not fully capture the complexity of TBI. For instance, some patients diagnosed with concussion experience ongoing, debilitating symptoms, yet are dismissed without follow-up care, while others diagnosed with severe TBI may lead full lives, despite families being advised to consider life-sustaining treatment withdrawal. Now, after over 50 years, TBI assessment is set for a significant update.

A new approach for assessing TBI is being tested at trauma centers across the United States, promising more accurate diagnoses and more appropriate treatment and follow-up care for patients. This new framework was developed by a coalition of experts and patients from 14 countries, including researchers from the University of California, San Francisco (UCSF, San Francisco, CA, USA and the Medical College of Wisconsin (Milwaukee, WI, USA. The updated framework goes beyond the immediate clinical symptoms to include additional criteria, such as biomarkers, CT and MRI scans, and factors like other medical conditions and the nature of the trauma. Clinicians believe this revised approach will lead to more precise diagnoses, providing more effective care for some patients while avoiding premature life support discussions for others.

The new framework, known as CBI-M, is detailed in Lancet Neurology and is built on four key pillars: clinical, biomarker, imaging, and modifiers. The clinical pillar retains the Glasgow Coma Scale’s score as a central element for assessing consciousness, pupil reactivity, and other symptoms such as amnesia, headache, dizziness, and noise sensitivity. This pillar expands upon the traditional GCS by including responses to eye, verbal, and motor commands or stimuli. The second pillar focuses on biomarkers detected in blood tests to provide objective signs of tissue damage, addressing the limitations of clinical assessments that might include symptoms unrelated to TBI. Crucially, low levels of these biomarkers help identify patients who do not need CT scans, reducing unnecessary radiation exposure and healthcare costs, while allowing for earlier discharge. For patients with more severe injuries, the third pillar involves the use of CT and MRI scans to detect blood clots, bleeding, and lesions that could signal both present and future symptoms.

Additionally, biomarkers can help identify patients suitable for clinical trials aimed at developing new TBI treatments, which have seen little progress in the past three decades. A recently launched trial across 18 trauma sites may finally lead to the development of new treatments for TBI. The final pillar, modifiers, takes into account how the injury occurred—whether from a fall, a blow, or sharp object penetration—and includes factors like pre-existing conditions, medications, health care access, prior TBIs, substance abuse, and living conditions. This pillar ensures that all these factors are considered when interpreting the patient’s clinical, biomarker, and neuroimaging results. For example, a patient with existing cognitive impairments may require closer monitoring for deterioration, regardless of their initial clinical assessment findings. The new framework is being gradually tested at trauma centers, where it will be refined and validated before full implementation.

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