The hidden lesion: multimodal forensic evaluation of diffuse axonal injury in traumatic brain death

Abstract Background Diffuse axonal injury (DAI) is a severe form of traumatic brain injury associated with high-velocity impact, acceleration–deceleration forces, and rotational trauma. Despite its clinical and forensic importance, DAI frequently eludes detection on gross examination at autopsy, rendering it a “hidden lesion” that necessitates microscopic evaluation and advanced neuroimaging for accurate diagnosis. In forensic practice, DAI plays a pivotal role in determining the mechanism and timing of injury, particularly in fatal trauma and suspected non-accidental head injury. This review aims to synthesize current evidence on the pathophysiology, neuropathological features, diagnostic modalities, and forensic and medicolegal implications of DAI in traumatic brain injury, with particular emphasis on its role in death investigation. Main body The pathophysiology of DAI involves shearing forces that disrupt axons at interfaces of differing brain densities, particularly within the corpus callosum, brainstem, and subcortical white matter. Histopathological findings include axonal swellings and retraction bulbs, with enhanced detection through immunohistochemical markers such as β-amyloid precursor protein (β-APP) and neurofilaments. Radiologically, magnetic resonance imaging (MRI) demonstrates superior sensitivity compared to computed tomography (CT), especially with advanced techniques including susceptibility-weighted imaging (SWI) and diffusion tensor imaging (DTI). From a forensic perspective, DAI is central to the evaluation of traumatic brain injury, including cases of abusive head trauma (AHT), where it contributes to the assessment of both mechanism and timing of injury. Conclusion Diffuse axonal injury remains a diagnostically challenging yet forensically significant entity in traumatic brain injury. Accurate identification requires a multidisciplinary approach integrating clinical context, advanced neuroimaging, and targeted histopathology. Improved recognition enhances the accuracy and reliability of medicolegal determinations, particularly in complex trauma and suspected abuse, reinforcing its value in forensic practice.