Traumatic axonal injury describes axonal injury directly attributable to trauma, usually involving acceleration and deceleration of the head. When widespread, the term diffuse (traumatic) axonal injury is used, and describes a clinicopathologic syndrome where patients are unconscious from the moment of injury and typically remain that way until death. Microscopically, early changes (2-4h) include focal axonal accumulations of amyloid precursor protein (identified by immunohistochemistry). By 12h, axonal varicosities may be evident on routine histology, appearing as eosinophilic spheroids. These can be highlighted by APP or neurofilament immunohistochemistry or by silver impregnation. Later findings include microglial clusters (weeks) and Wallerian degeneration with loss of myelinated fibres (months). The main regions affected are the superior parasagittal white matter, corpus callosum, subcortical white matter, and brainstem white matter tracts. In this case, axonal spheroids can be seen in the superior cerebellar peduncle, cerebral peduncle (corticospinal tract), medial lemniscus, and central tegmental tract. See Related Content for labelled diagram of midbrain structures.