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Introduction¹

Traumatic brain injury (TBI) is a complex condition with differing mechanisms and severities of injury, affecting all ages and populations. This heterogeneity makes it challenging to accurately assess injury, effectively deliver care, and optimize outcomes for people and families that experience a TBI. To advance care and research, an ongoing goal for the field has been to identify and validate a tool kit of biomarkers that are able to more precisely and objectively diagnose and categorize a suspected TBI, better guide and monitor treatment and recovery after injury, and refine the design of future research studies. This remains an active and important area of investigation and clinical implementation.

There are four major classes of biomarkers applicable to TBI: markers identifiable through neuroimaging, proteins that can be measured in blood and other bodily fluids, electrophysiological indicators, and other types of physiological markers that can be identified by using sensors. These biomarkers are in various stages of development—neuroimaging through computed tomography (CT) and magnetic resonance imaging (MRI) are frequently used after a head injury, and the TBI field continues to refine methods for visualizing the signatures of brain injury in greater detail. A variety of blood-based biomarkers are actively being researched, with

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¹ The planning committee’s role was limited to planning the workshop, and the Proceedings of a Workshop has been prepared by the workshop rapporteurs as a factual summary of what occurred at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants and are not necessarily endorsed or verified by the National Academies of Sciences, Engineering, and Medicine, and they should not be construed as reflecting any group consensus.

assays measuring several proteins available for use in acute TBI evaluation. But further progress remains to continue developing and refining available tools, validating existing biomarkers in expanded contexts of use, and investigating new types of sensors and markers. These developments and remaining questions and needs are summarized in this proceedings.

TBI CONTINUUM OF CARE

As a recent report from the National Academies described, a person can experience a complex journey after a TBI, involving multiple phases of care and recovery (see Figure 1-1; NASEM, 2022). Depending on the nature and severity of the injury, the stages of care include recognition of the injury, which may involve prehospital assessment by emergency medical services (EMS); acute care and classification of the nature of the TBI in settings such as emergency departments; provision of rehabilitation interventions and ongoing follow-up; and longer-term recovery and reintegration back into society.

Some people recover quickly from a TBI, but for many the journey is not continuous, and barriers or setbacks may be encountered along the way. While details of the care pathway depend on the injury and how and where it was experienced (e.g., sports-related event, assault, military service, or civilian accident), the development of guidance, interventions, and tools applicable at each stage of the recovery process is important to achieve the best possible outcomes for patients and families. Workshop discussions also touched on the persistence of symptoms, use of biomarkers, and recovery from TBI at different time points after injury—including acute, post-acute, and chronic periods. The workshop did not define these periods precisely, but as defined by the moderator of the final session, they can generally be considered as approximately within the first few days (acute), from 3 days to 6 months (post-acute), and over 6 months (chronic or long term).

BIOMARKER CONSIDERATIONS

Stuart Hoffman, Department of Veterans Affairs, introduced the theme of the workshop. No single biomarker is likely to capture the full pathophysiology of all traumatic brain injuries across all phases of care, particularly the dynamic and longer-term nature of recovery. Approaches to analyze and monitor information from multiple sources are necessary, as well as the continued translation and effective implementation of biomarkers into clinical practice. These efforts may include additional validation of biomarker candidates across diverse patient populations (including in children and older adults, as well as patients across the spectrum of injury mechanisms and severities) and the incorporation of approved biomarkers into TBI classification and into clinical guidance in different care settings. Hoffman shared key dimensions of biomarkers that will need to be considered when assessing their uses for TBI care and research; these are summarized in Figure 1-2 and include the type of marker, purpose to which the marker can be applied, and the phase of care during which the marker’s information is most relevant.

ORGANIZATION OF THE WORKSHOP

The newly created Forum on Traumatic Brain Injury at the National Academies of Sciences, Engineering, and Medicine hosted a 1-day workshop that explored the use of biomarkers to diagnose and classify a suspected TBI, guide and monitor treatment after injury, and refine future research studies. The workshop presentations and discussions summarized the landscape of TBI biomarkers, described the impact that biomarkers can have on phases of TBI care and research, and identified potential opportunities to further advance the field.

The workshop was held virtually and in person on September 29, 2022. The first session introduced the workshop topics and provided examples of clinical needs that may be addressed through further biomarker development and implementation. Later sessions explored the state of the science in major classes of biomarkers, the research and development pathways, and opportunities for advancing biomarker use, including emerging initiatives at the national level. Finally, discussions centered on where the TBI community wants to go moving forward and how to realize these goals. Appendix A contains the reference list. See Appendix B for the workshop statement of task and agenda and Appendix C for brief biographies of speakers and planning committee members.

ORGANIZATION OF THE PROCEEDINGS

This proceedings summarizes presentations and discussions during the workshop and is organized into five chapters. Following the introduction, Chapter 2 discusses examples of unmet needs in care and research identified by the TBI community, along with lessons from the development and use

of biomarkers in cardiac care. Chapter 3 outlines the state of the science for neuroimaging markers, blood-based biomarkers, electrophysiological markers, and other physiological indicators. Chapter 4 highlights several near-term opportunities to advance the implementation of biomarkers in TBI clinical practice, including an updated classification approach. Finally, Chapter 5 identifies thematic areas and key messages discussed by workshop speakers and participants during the meeting, along with remaining challenges and questions to be addressed.

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