Integrative Diagnostic and Prognostic Paradigms in Diffuse Axonal Injury: Insights from Clinical, Histopathological, Biomolecular, Radiological, and AI-Based Perspectives

Diffuse axonal injury (DAI) is one of the most severe consequences of traumatic brain injury (TBI), characterized by widespread axonal damage in the cerebral white matter. DAI plays a crucial role in determining clinical outcomes, significantly contributing to long-term disability and mortality in severe cases. Despite advancements in neuroscience and clinical management, the diagnosis and prognosis of DAI remain challenging due to its complex pathophysiology and the difficulty of detecting axonal damage in its early stages. This study critically analyzes the clinical and post-mortem methodologies used to assess DAI, highlighting their strengths and limitations. Traditional histopathological grading systems provide valuable insights into disease progression, yet their correlation with long-term functional outcomes remains controversial. Advanced neuroimaging techniques, such as diffusion-weighted MRI, have improved lesion detection, although their routine clinical application is still limited. Additionally, emerging approaches involving biomarkers and artificial intelligence-based models hold promise for enhancing diagnostic accuracy and prognostic predictions. By synthesizing current knowledge on DAI, this work aims to outline a comprehensive framework for improving diagnosis and outcome assessment. Furthermore, it seeks to foster collaboration among clinicians and researchers, ultimately advancing the understanding of DAI and refining strategies to improve patient care.