Pathological Spectrum and β-APP Immunoreactivity as a Diagnostic Tool of Diffuse Axonal Injury following Traumatic Brain Injury: A Novel Classification.

 Different deposition patterns and grading systems used to define and identify DAI remain discordant and to date these are a challenge in clinical practice. Our main objective was to study the post-mortem axonal changes and develop a grading system to identify DAI on the basis of histopathological and immunoreactive β-amyloid precursor protein (β-APP) observations in severe TBI cases.  Prospective study with 35 decedents with sTBI (GCS score ≤ 8) was conducted and samples were collected from three different sites-corpus callosum, thalamus and brain stem. Serial sections from each site were stained with hematoxylin and eosin (H&E), and immunohistochemistry (IHC) of β-APP.  We developed a grading system based on histopathological characteristics to assess the overall damage of axonal injury. We found maximum histopathological changes in cases with prolonged stay. Corpus callosum showed maximum changes in both gradings. Curiously, we also detected axonal swellings with H&E staining. Usually neglected, the thalamus also showed significant histopathological and immunoreactive changes for sTBI.  Our study based on histopathological and β-APP scoring system to define and identify DAI thus facilitates accurate diagnosis of DAI post mortem, which has forensic implications, and may further contribute toward survival and improvement of quality of life of sTBI patients.