Marking a New Age in Characterization of Acute Traumatic Brain Injury: The National Institute of Neurological Disorders and Stroke Traumatic Brain Injury Classification and Nomenclature Initiative

Abstract

This special issue of the Journal of Neurotrauma features a series of articles reporting the findings and recommendations of each of the six NINDS Initiative Working Groups. The collective efforts of the Working Groups with input from the broader TBI community mark a major step toward gaining more precise characterization of TBI and offer significant advantages over the current state of characterization for both clinicians, researchers, and people with lived experience. On behalf of all those who contributed to what marks a new era of improved characterization of TBI, we express our gratitude to NINDS for spearheading this effort and to the Journal of Neurotrauma for showcasing this important work.

Longstanding challenges inherent to the diagnosis, prognosis, and treatment of traumatic brain injury (TBI) are all too familiar to neurotrauma clinicians and researchers, most notably the Journal of Neurotrauma readership. Several decades of progress have substantially advanced our scientific understanding of the complex pathophysiology of TBI, and major technological advances in imaging and biomarkers can now aid in its evaluation and treatment. However, approaches to acute characterization and classification of TBI remain very rudimentary, stymieing efforts to develop targeted treatments and more accurate and actionable prognosis.

TBI is most commonly classified according to the Glasgow Coma Scale (GCS) as mild (GCS 13–15), moderate (GCS 9–12), or severe (GCS ≤8). While the value of the GCS since its inception 50 years ago is without question, the limitations of a unidimensional approach to classifying TBI based on the GCS sum score alone are widely known to clinicians, researchers, patients, and caregivers alike. In the age of precision medicine, no modern treatable condition is reduced to a nomenclature of “mild, moderate, severe,” certainly none as complex and heterogenous as TBI. This nomenclature can also be misleading (e.g., when a “mild” TBI results in chronic symptoms and disability). Furthermore, these categories are of limited pathophysiological relevance and are therefore poorly suited to informing treatments or clinical trial stratification. The need for an improved system for classification of TBI was underscored as one of the main recommendations in a 2022 report of the National Academies of Science, Engineering and Medicine (NASEM), entitled “Traumatic Brain Injury: A Roadmap for Accelerating Progress.”

In response to the NASEM call, the National Institute of Neurological Disorders and Stroke (NINDS) launched an initiative in the fall of 2022 to develop a novel comprehensive TBI classification and nomenclature framework and to identify research topics that may inform further refinement and updating of this new framework. This global effort was undertaken with contributions from nearly 100 TBI clinicians, researchers, federal partners, and people with lived experience. As part of this effort, dedicated Working Groups were formed to gather multidisciplinary expertise to select elements critical to realizing an improved system for characterization and classification of TBI, culminating in a publicly open NINDS workshop hosted in January 2024.

A major output of this initiative was the development of a new framework ¹ for the characterization of TBI in the early, acute (first 24 h) phase: The “CBI-M” framework integrates four pillars: Clinical (full GCS and pupillary reactivity), ² Biomarkers (blood-based biomarkers), ³ Imaging (pathoanatomical features), ⁴ and Modifiers (patient modifiers that affect clinical presentation and outcome). ⁵ This framework represents a multidimensional approach that is applicable across all injury severities in the acute phase and marks a major improvement over existing approaches. The NINDS Initiative, however, went beyond characterization in the acute phase and also addressed subacute and chronic phases, ⁶ as well as retrospective classification when patients do not present for evaluation during the acute phase. Finally, the initiative also addressed strategies for successful implementation of recommendations into clinical practice and applied research. ⁷

This special issue of the Journal of Neurotrauma features a series of articles reporting the findings and recommendations of each of the six NINDS Initiative Working Groups. The collective efforts of the Working Groups with input from the broader TBI community mark a major step toward gaining more precise characterization of TBI and offer significant advantages over the current state of characterization for clinicians, researchers, and people with lived experience.

On behalf of all those who contributed to what marks a new era of improved characterization of TBI, we express our gratitude to NINDS for spearheading this effort and to the Journal of Neurotrauma for showcasing this important work.