Introduction
Background
Diffuse axonal injury (DAI) is a frequent result of traumatic deceleration injuries and a frequent cause of persistent vegetative state in patients. DAI is the most significant cause of morbidity in patients with traumatic brain injuries, which most commonly result from high-speed motor vehicle accidents.
DAI is a significant medical problem because of the high level of debilitation that is suffered by the patient, the stress that must be endured by the patient's family when the patient is in a persistent vegetative state, and the staggering medical cost of sustaining the patient in this state. DAI typically consists of several focal white-matter lesions measuring 1-15 mm in a characteristic distribution (see below).
Pathophysiology
The pathophysiology of DAI first was described by Holbourn in 1943, using 2-dimensional gelatin molds.1 His work led to the understanding that shear injury is not induced by linear or translational forces but rather by rotational forces. Sudden acceleration-deceleration impact can produce rotational forces that affect the brain. The injury to tissue is the greatest in those areas where the density difference is the greatest. For this reason, approximately two thirds of DAI lesions occur at the gray-white matter junction.
When shearing forces occur in areas of greater density differential, the axons suffer trauma; this results in edema and in axoplasmic leakage (which is most severe during the first 2 weeks following injury). The exact location of the shear-strain injury depends on the plane of rotation and is independent of the distance from the center of rotation. Conversely, the magnitude of injury depends on the following 3 factors:
- The distance from the center of rotation
- The arc of rotation
- The duration and intensity of the force
The true extent of axonal injury typically is worse than that visualized using current imaging techniques. On the microscopic level, the axon may not be completely torn by the initial force, but the trauma still can produce focal alteration of the axoplasmic membrane, resulting in impairment of axoplasmic transport. This would lead to axoplasmic swelling, with the axon subsequently splitting into 2 pieces and a retraction ball — a pathologic hallmark of shearing injury — forming. The axon would then undergo wallerian degeneration. Dendritic restructuring might occur, with some regeneration possible in mild to moderate injury.
Within the basal ganglia, the effect of DAI produces parenchymal atrophy brought on by shrinkage of astrocytes in the lateral and ventral nuclei, with sparing of the anterior and dorsomedial nuclei, the pulvinar, the centromedian nuclei, and the lateral geniculate bodies. Cholinergic neurons have been found to be slightly more susceptible to trauma than are neurons belonging to other neurotransmitters. Peripheral lesions usually are smaller than central lesions. The lesions typically are ovoid or elliptical, with the long axis parallel to the direction of the involved axonal tracts. A high association is seen between thalamic injury and DAI.
Both silver staining and beta-amyloid precursor protein immunohistochemical staining have proven useful in the pathologic identification of DAI lesions.
DAI was classically believed to represent a primary injury (occurring at the instant that the trauma occurred). It has become apparent, however, that the axoplasmic membrane alteration, transport impairment, and retraction ball formation may represent secondary (or delayed) components of the disease process.
Frequency
United States
DAI represents approximately one half of all intra-axial traumatic lesions.
Mortality/Morbidity
DAI rarely results in death. As many as 90% of patients remain in a persistent vegetative state.
Race
No racial predilection exists.
Sex
No sex predilection exists.
Age
DAI can occur at any age. Some studies suggest that DAI may occur in utero if a pregnant woman is subjected to sufficient force.
Anatomy
Typically, the process is diffuse and bilateral, involving the lobar white matter at the gray-white matter interface. The corpus callosum frequently is involved, as is the dorsolateral rostral brainstem. The most commonly involved area is the frontal and temporal white matter, followed by the posterior body and splenium of the corpus callosum, as well as the caudate nuclei, thalamus, tegmentum, and internal capsule. Internal capsule lesions are associated more frequently with hemorrhage than are the other lesions and are secondary to the proximity of the lenticulostriate vessels.The following stages of involvement have been described by Adams and colleagues according to the anatomic location of the lesions4 :
- Stage I - This involves the parasagittal regions of the frontal lobes, the periventricular temporal lobes, and, less likely, the parietal and occipital lobes, internal and external capsules, and cerebellum.
- Stage II - This involves the corpus callosum in addition to the white-matter areas of stage I. Stage II is observed in approximately 20% of patients. Most commonly, the posterior body and splenium are involved; however, the process is believed to advance anteriorly with increasing severity of disease. Both sides of the corpus callosum may be involved; however, involvement more frequently is unilateral and may be hemorrhagic. The involvement of the corpus callosum carries a poorer prognosis.
- Stage III - This involves the areas associated with stage II, with the addition of brainstem involvement. A predilection exists for the superior cerebellar peduncles, medial lemnisci, and corticospinal tracts.
Presentation
Classically, DAI has been considered a primary-type injury, with damage occurring at the time of the accident. Research has shown that another component of the injury comprises the secondary factors (or delayed component), since the axons are injured, secondary swelling occurs, and retraction bulbs form. Of patients with DAI, 80% demonstrate multiple areas of injury on computed tomography (CT) scans.
The degree of microscopic injury usually is considered to be greater than that seen on diagnostic imaging, and the clinical findings reflect this point. DAI is suggested in any patient who demonstrates clinical symptoms disproportionate to his or her CT-scan findings. DAI results in instantaneous loss of consciousness, and most patients (>90%) remain in a persistent vegetative state, since brainstem function typically remains unaffected. DAI rarely causes death.
Compared with patients who have an epidural hematoma, patients with DAI are less likely to have a lucid interval. There is little association between DAI and the presence of skull fractures; in addition, the existence of DAI has no bearing on whether a subarachnoid or subdural hemorrhage is present.
The chance that a patient will remain in a persistent vegetative state is greater when lesions are observed in the supratentorial white matter, corpus callosum, and corona radiata. The prognosis also worsens as the number of lesions increases. For the almost 10% of patients who experience a return to any form of normal function, this improvement will be seen within the first year. DAI lesions can result in deficits in information transfer between the 2 sides of the corpus callosum, commonly resulting in auditory deficits.
Preferred Examination
Magnetic resonance imaging (MRI) is the preferred examination for DAI (particularly with gradient-echo sequences), although CT scanning may demonstrate findings suggestive of DAI and is more practical and available. Studies have indicated that MRI can play a role in predicting the length of coma in DAI patients.
Limitations of Techniques
MRI is contraindicated in patients with implanted pacemakers or certain types of metallic prostheses, as well as in patients who have metallic foreign bodies, such as bullet fragments, in their head or neck or near important vascular structures. In addition, MRI is difficult to perform on patients who have claustrophobia and on ventilator-dependent patients.
Differential Diagnoses
Other Problems to Be Considered
Cavernous angioma of the brain
Embolic and/or hemorrhagic stroke
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References
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Further Reading
Keywords
DAI, axonal shear injury, axonal shear-strain injury, traumatic brain injuries
