diffuse brain injury
Four forms of diffuse brain injury may be seen as a consequence of head trauma:
- diffuse iscahemic injury (grey matter);
- diffuse vascular injury;
- diffuse traumatic axonal injury (TAI) (white matter); and
- brain swelling/ oedema.
diffuse ischaemic injury
Focal infarcts are commonly seen after fatal traumatic head injury, and are usually the result of raised intra-cranial pressure. Global ischaemia is less common, and may follow hypotension (e.g. in polytrauma) or massive raised intra-cranial pressure causing reduced cerebral blood flow.
Neurones are selectively vulnerable to the effects of hypoxia/ ischaemia - those most vulnerable being those in the CA1 region of the hippocampi, the cerebellar Purkinje cells and those in layers 3,5 and 6 of the cortex.
The cytoplasm of ischaemic neurones can be a red colour, and the nucleus is generally shrunken and pyknotic. Changes appear within 4-6 hours post-insult, but can be difficult to differentiate from artefact. Vacuolation of the background neuropil may be of assistance in diagnosing hypoxic/ ischaemic encephalopathy.
diffuse vascular injury
This entity consists of multiple small haemorrhages throughout the brain, and is virtually confined to those dying within 24 hours of head injury.
diffuse traumatic axonal injury (TAI)
TAI is a microscopic diagnosis, but can be inferred by the existence of morphological 'markers':
- petechial haemorrhages in the corpus callosum;
- petechial haemorrhages within the dorsolateral quadrants of the rostral brainstem (in an adjacent to the superior cerebellar peduncles); and
- gliding contusions in the para-sagittal white matter of the superior cerebral hemispheres
The mechanism of TAI appears to be shearing forces causing either a primary axotomy (immediate disruption of the axon) or secondary/ delayed axotomy a few hours after the traumatic insult.
Axonal damage is identified by conventional microscopy after approximately 12-24 hours, in the form of axonal swellings or varicosities (optimally visualised by silver stains, but visible as eosinophilic swellings on H&E).
More recently, it has been recognised that ß-amyloid precursor protein (APP) - a uniquitous membraneglycoprotein produced in the cell body and transported by fast anterograde axoplasmic flow - accumulates at the site of axonal damage, and can be identified by immunohistochemistry.
Researchers have shown APP positivity in damaged axons in human brains as early as 1.5 hours post-injury, whilst animal studies have shown earlier positivity. Some researchers claim to have demonstrated APP positivity as early as 35 minutes, utilising antigen retrieval methods; it remains to be seen whether these results can be replicated.
APP positivity highlights axonal damage, but it is not specific to traumatic damage - axons damaged by hypoxia/ ischaemia have also been shown to be positive, and although it is sometimes claimed that a distinction can be made between the 2 modes of axonal injury - based on the pattern of staining - this is not always a straight-forward matter.
Microscopic sampling of fixed brains should follow recommended protocols for demonstrating TAI in head injury fatalities.
Diffuse axonal injury (Wikipedia)
Diffuse axonal injury radiology (Radiopedia.org)
cerebral oedema and intracranial pressure
cerebral oedema after a drugs overdose (from Radiopedia.org)
Brain swelling due to the development of cerebral oedema is a common sequelae of head injury, and leads to raised intra-cranial pressure (normally less than 20 mmHg; >60 mmHg being fatal).
Oedema mainly affects the white matter, resulting in flattening of the gyri against a tense and bulging dura.
Swelling forces the brain against the rigid reflections of the dura within the skull, leading to 'herniation',
- through external defects (including 'bone flaps' raised by neurosurgeons)
- under the falx (para-sagittal)
- under the tentorium (uncal)
- through the foramen magnum (cerebellar herniation or 'coning')
Global brain swelling (flattened gyral crests and obliteration of sulci)
