Diffuse Axonal Injury

Diffuse Axonal Injury

Diffuse axonal injury (DAI) is the second most common parenchymal lesion seen
in traumatic brain injury, exceeded only by cortical contusions. Patients with DAI
often exhibit an apparent discrepancy between clinical status (often moderately to
severely impaired) and initial imaging findings (often normal or minimally
abnormal).
Terminology
Diffuse axonal injury is also known as traumatic axonal stretch injury. As most
DAIs are stretch-not frank shearing-lesions, the term shearing lesion should be
avoided. True shearing injury with frank axonal disconnection is uncommon
and typically occurs only with very severe trauma.
Etiologi:
Direct head impact is not required to produce DAI. Most DAIs are not associated
with skull fracture.
Most DAIs are caused by high-velocity auto accidents and are non-impact
injuries resulting from the inertial forces of rotation generated by sudden changes
in acceleration/deceleration. The cortex moves at different speed in relationship to
underlying deep brain structures (white matter, deep gray nuclei). This results in
axonal stretching, especially where brain tissues of different density intersect,i.e,
the gray-white matter interface.
Traumatic axonal stretching causes impaired axoplasmic transport, depolarization,
ion fluxes, spreading depression, and release of excitatory amino acids. Celular
swelling with citotoxic edema ensues, altering anisotropy of the brain. Significant
and widespread alterations of brain metabolites occur as a result of traumatic brain
injury (TBI).
Patologi
Locations. DAIs occurs in highly predictable locations. The cortex is typically
spared;it is the subcortical and deep white matter tracts such as the corpus
callosum, especially the genu and splenium, fornix, and internal capsule, are less
common sites of DAI (2-67,2-68).

2-67. Sagital graphic depicts common sites of axonal injury in the corpus
callosum and midbrain. Traumatic intraventicular and subarachnoid hemorrhage is
present.
2-68. Graphics depict the most common sites of axonal injury in red. Frequent but
relatively less common locations are shown in green. Injury to the midbrain/upper
pons(purple) is uncommon but often lethal.

Gross patologi
The vast majority of DAIs are microscopic and nonhemorrhagic. Tears of
penetrazing vessels may cause small round to ovoid or linear hemorrhanges that
sometimes are the only gross indications of underlying axonal injury (2-69).
These visible lesions are truly just the "tip of the iceberg".
Microscopic features. axonal swellings or "retractions balls" form, leaving
microscopic gaps in white matter (2-70). Neuronal apoptosis and microglial
reaction ensue. Chronic upregulation of activated microglial immunoreactive for
galectin -3/mac -2 and nerve growth factor has been demostrated following DAI.

2-69. A utopsy case shows typical findings of diffuse axonal injury with
linear hemorrhages in the subcortical and deep periventricular white
matter
2-70. H & E microscopy shows numerous white gaps or bare areas
caused by axonal injury.
(Courtesy R. Hewlett, MD.)
2-71 A. NECT in a partienr with severe nonimpact head injury shows
diffuse brain swelling with small ventricles, effaced sulci and cisterns.
DAIis present, seen as several punctate and linier hemorrhagic foci in the
subcortical WM, midbrain, and left thalamus
2-71 B. More cephalad scan in the same patients shows additional
hemorrhagic foci in the corona radiata , subcortical WM

Staging, grading and classification. The adams and gennarelli classification

defines mild,moderate,severe grades of TBI.
In mild TBI, lesions are seen in the frontotemporal gray-white matter
interfaces,injury is designated as moderate when the lobar white matter and
corpus callosum are affected. In severe TBI, lesions are present in the dorsolateral
midbrain and upper pons. More than half of all TBI cases with DaI are designated
as moderate to severe.

Clinical issues
Epidemiologi and demografi. DaI is present in vistually all fatal TBIs and is
found in almost three quarters of patients with moderate or severe injury who
survive the acute stage. DaI may occur at any age,but peak incidence is in young
adults (15-24 years old). Males are at least twice as often afflicted with TBI as
females.
Presentation
DaI typically causes much more significant impairment compared to extracerebral
hematomas and cortical contusions. DAI often causes immediate loss of
consciousness (LOC). LOC may be transient (in the case of mild TBI) or progress
to coma (with moderate to severe injury)
Natural History. Mild TBI may result in persisting headaches, mild
neurocognitive impairment, and memory difficulties. DAI is more common in
moderate to severe injuries. While DAI itself rarely causes death, severe DAI may
result in persistent vegetative state. Prognosis correlates with thenumber anf
severity of lesions as well as the presence of other abnormalities such as cortical
contusions and herniation syndromes.
Treatment Options. Management of intracranial pressure is the most serious
issue. In some cases with impending herniation, craniectomy may be a last resort.
Imaging
General features. One of the most striking features of DAI is the discrepancy
between clinical symptoms and imaging findings. NECT scans are almost always
the initial imaging study obtained in TBI (2-71), although MR is much more
sensitive in detecting changes of DAI. CT is very useful in detecting comorbid
injuries such as extracerebral hemorrhage and parenchymal hematomas.
DAI typically evolves with time, si lesions are usually more apparent on followup scans. Between 10-20% evolve to gross hemorrhages with edema and mass
effect.
CT Findings. Initial NECT is often normal or minimally abnormal (2-72A). mild
diffuse brain swelling with sulcal effacement may be present. Gross hemorrhages
are uncommon immediately following injury. A few small round or ovoid
subcortical hemorrhages may be visible (2-71), but the underlying damage is
typically much more diffuse and much more severe than these relatively modest
abnormalities would indicate.

MR Findings. As most DAIs are nonhemorrhagic, TI scan are often normal,

especially in the early stages of TBI. T2WI and FLAIR may show hyperintense
foci in the subcortical white matter and corpus callosum. Multiple lesions are the
rule, and a combination of DAI and ci=ontusions or hemoatomas is very common.
T2* scans are very sensitive to the microbleeds of DAI and tipically show
multifocal ovoid and linear hypointensities (2-72B). SWI sequences typically
demonstrate more lesions than GRE. Residua from DAI may persist for years
following the traumatic episode.
DWI may show restricted diffusion, particularly within the corpus callosum (273). DTI tractography may be useful in depicting white matter disruption. MRS
shows widespread decrease of NAA with increased Cho.

2-72 A. NECT scan in a patient wiyh closed head injury from high-speed motor
vehicle collision shows no definite abnormalities.
2-72 B. Because of the discrepancy between imaging findings and the patients
clinical status (GCS = 8), MR was obtained. T2* GRE scan shiws multiple

blooming foci in the subcortical/deep white matter and corpus callosum ,

characteristic of hemorrhagic axonal injury.
2-73 A. NECT scan in a head trauma patient with low GCS shows diffuse brain
swelling with small vantricles, sulcal effacement. Hyperdense foci in the deep
gray nuclei and fornix suggest axonal injury.
2-73 B. DWI in the same patient shows restricted diffusion in the right fornix
and corpus callosum
, characteristicof diffuse axonal injury.

Differential Diagnosis
Cortical contusions often coexist with DAI in moderate to severe TBI. Cortical
contusions are typically superficial lesions, usually located along gyral crests.
Multifocal hemorrhages with blooming on T2* (GRE, SWI) scan can be seen in
numerous pathologies, including DAI. Diffuse vascular injury (see below)
appears as multifocal parenchymal black dots. Pneumocephalus may cause
multifocal blooming lesions in the subarachnoid spaces. Parenchymal lesions
are rare.
Several nontraimatic lesions also appear as multifocal T2* parenchymal
hypointensities. Cerebral amyloid angiography and chronic hypertensive
encephalopathy are common in older patients. Zabramski type 4 cavernous
malformation are also seen as black dots on T2* MR scans