BRIDGE-US: Bridging Readiness in Deployed Neurotrauma Gaps for Excellence

Penetrating brain injury (PBI) is one of the most devastating and understudied forms of traumatic brain injury (TBI), characterized by the violation of the skull and brain parenchyma by foreign objects such as bullets or shrapnel. Unlike blunt TBI, PBI involves unique mechanical and secondary injury patterns, including direct tissue destruction, vascular damage, hemorrhage, cavitation, and axonal shearing. These injuries often lead to severe disability or death, particularly in military and civilian populations exposed to ballistic trauma. Despite the increasing burden of firearm-related PBI in civilian trauma centers and the operational relevance in military settings, there remains a significant lack of structured data, standardized terminology, and biological understanding to guide prognostication or treatment decisions. This knowledge gap has fostered therapeutic nihilism, resulting in high rates of early withdrawal of life-sustaining therapies and a lack of targeted clinical pathways for these patients.

Emerging biomarker research in blunt TBI has identified several promising molecular indicators that reflect different aspects of brain injury. These include S100 calcium-binding protein B (S100B), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and neurofilament light chain (NFL), which are associated with glial activation, neuronal injury, and axonal damage, respectively. Elevated levels of GFAP and UCH-L1, for example, have been correlated with injury severity and poor outcomes in both civilian and military TBI populations, while NFL has shown potential as a predictor of long-term cognitive deficits. However, biomarker data specific to PBI is extremely limited. The distinct mechanical forces and injury patterns of PBI suggest that biomarker profiles may differ significantly from those seen in blunt trauma, highlighting the need for focused investigation. The temporal profiles of biomarkers have been assessed in blunt TBI but not in PBI. Advancing biomarker discovery in PBI could help identify patients at risk of poor outcomes, support early clinical decision-making, and differentiate PBI from overlapping conditions.

Beyond molecular markers, imaging plays a critical role in the diagnosis and management of PBI. High-resolution structural imaging, including computed tomography (CT) and advanced magnetic resonance imaging (MRI) techniques such as diffusion tensor imaging (DTI), provides critical insights into the extent of parenchymal damage, vascular injury, and axonal disruption. However, imaging access is often limited in prehospital or austere environments, especially in military settings. A combined approach leveraging clinical data, biomarkers, and imaging holds promise for improving the characterization of PBI and guiding treatment decisions across care environments.

The study's integrated approach will create the infrastructure necessary to close critical knowledge gaps, advance biomarker discovery specific to PBI, and provide the foundation for future research aimed at improving prognostication and treatment for patients with this devastating injury.

Inclusion criteria

• Age: Subjects aged 16 years and older
• Injury Type/Evidence: Patients with a confirmed PBI as demonstrated by head imaging or physical exam (evidence of dural penetration by a projectile)
• Timeframe: Patients must be enrolled within 8 hours of injury

Exclusion criteria

No subjects will be excluded based on gender or ethnicity for this study. Subjects under the age of 16 will be excluded. These subjects differ significantly in terms of neurodevelopment, physiology, and trauma response, which introduces heterogeneity that could confound study results. Additionally, pediatric PBI has distinct etiologies, treatment pathways, and prognostic indicators compared to adult PBI (note that age 16 and up are treated medically as adults).

FULL EXCLUSION CRITERIA:

• Dead on Arrival (DOA): Patients who receive CPR with no return of pulse
• Non-penetrating injury: Patients with head injuries that do not include dural penetration
• Polytrauma: Patients with penetrating or blunt injuries to other parts of the body
• Known or suspected pregnancy
• Known or suspected prisoner