Introduction
Diffuse Axonal Injury (DAI) is considered one of the most common and detrimental forms of traumatic brain injury (TBI).
The resistant inertia that occurs to the brain at the time of injury, preceding and following its sudden acceleration against the solid skull, causes shearing of the axonal tracts of the white matter.
Road traffic accidents (RTAs) are the most frequent cause of DAI, with assault or falls also common aetiologies. DAI may also present as a consequence of child abuse, particularly in shaken baby syndrome and abusive head trauma.
The patient population most susceptible to DAI is the equivalent cohort most vulnerable to traumatic brain injury, thus young males are often significantly over-represented.
Grading Classification
A classification for grading of DAI characterises into 3 distinct categories, based upon histological findings in the anatomical distribution of injury:
| Grade | Pathology |
Effect on Consciousness |
| Grade 1 | Diffuse axonal damage within the white matter of the cerebral hemispheres and grey-white matter interfaces | Brief loss of consciousness |
| Grade 2 | Tissue tear haemorrhages present; axonal damage of the white matter including grade 1 regions and the territory of the corpus callosum | Variable recovery process, coma of unclear duration |
| Grade 3 | Grade 2 findings in addition to tissue tear haemorrhages within the brainstem | Instant coma with posturing and incomplete recovery |
Pathophysiology
From the initial event or insult (e.g. accident, fall, assault), the rapid acceleration or deceleration of the head results in traumatic shearing forces. The grey and white matter of the axons are of distinct specific gravities, therefore the axons present at the grey-white matter junction are particularly susceptible to injury.
Axonal disconnection and mechanical disruption to axonal cytoskeletal structure results in immediate severe brain injury. Destroyed axon microtubules will align incorrectly, with Tau and amyloid precursor protein (APP) are aberrantly deposited.
The delayed secondary axonal disconnection develops in a progressive manner, accounting for a significant proportion of DAI damage. Secondary physiological alterations include disrupted axonal transport, diffuse swelling, and axonal degeneration.
Figure 1 – The three parts of the brainstem
Histopathology
The pathognomonic histological findings of axons with DAI are:
- Axonal varicosities – periodic swelling along the axonal length at the site of injury, secondary to the interrupted axonal transport
- Axonal bulb – Single large swellings at the site of disconnection, following complete axonal severance
Clinical Features
Patients will have loss of consciousness at the time of injury with a prolonged post-traumatic coma (often attributed to co-existent injury, e.g. acute haemorrhage or cerebral contusions)
The diagnosis is often only suspected when patients do not make a neurological recovery, based on initial imaging.
Differential Diagnoses
The main differential in cases of head injury are cortical contusions, typically found superficially at the cortical level, not concentrated to the grey-white matter junction.
Other differential diagnoses, from imaging, include diffuse vascular injury, amyloid angiopathy, and chronic hypertensive encephalopathy
Imaging
Whilst non-contrast CT imaging of the head is the mainstay initial investigation following head injury, DAI is poorly picked up through this modality. Even severe cases of DAI can have relatively normal CT imaging.
MRI imaging serves as the best imaging modality for DAI detection. Artefact regions are seen at the junctions of the grey-white matter, such as in the corpus callosum or brainstem.
Figure 2 – MRI imaging demonstrating diffuse axonal injury following motorcycle accident (day 3)
Management
Following any trauma, patients should be appropriately resuscitated and stabilised, prior to transfer to a neuro-trauma centre.
Therapeutic interventions for DAI are limited. Treatment options are all aimed to preventing secondary effects such as cerebral oedema or haemorrhage, however guidelines in treatment for DAI are variable
Patients will warrant close monitoring, including intracranial pressure monitoring, however the role of surgical intervention is also variable.
Management via steroids and short-term anticonvulsant therapy can be considered on a case by case basis.
Physiotherapy, speech therapy, and occupational therapy within brain injury rehabilitation programs should be provided to optimise patient follow-up.
Prognosis
A spectrum of clinical consequences may follow DAI, dependent on the severity of the pathology ranging from very minor to extensively diffuse damage.
Long-term vegetative state appears at the severe end of the spectrum. There is a predictive correlation between the extent of brainstem DAI and likelihood of persistent vegetative state.
Key Points
- Diffuse Axonal Injury is often fatal and one of the major causes of morbidity and mortality following traumatic brain injury
- Diffuse white matter tract lesions are histopathological and neuroimaging hallmarks of DAI
- A spectrum of severity for DAI exists, ranging from concussion in milder forms to coma in cases involving widespread axonal damage
- Treatment options are limited to preventing secondary effects such as cerebral oedema or haemorrhage.
