Diffuse Axonal Injury

Diffuse Axonal InjuryDiffuse 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).

PatologiLocations. 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).

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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 patologiThe 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.

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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.

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Clinical issuesEpidemiologi 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.

PresentationDaI 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 follow-up 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.

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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 (2-73). 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

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“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 DiagnosisCortical 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

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