eMedicine Specialties > Radiology > Brain/Spine

Diffuse Axonal Injury

Jeffrey R Wasserman, DO, Staff Physician, Department of Diagnostic Radiology, Medical College of Pennsylvania-Hahnemann University Hospital
Robert A Koenigsberg, DO, MSc, FAOCR, Director of Neuroradiology, Professor, Department of Radiology, Drexel University College of Medicine

Updated: Jul 26, 2007

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

Brain, Multiple Sclerosis

Other Problems to Be Considered

Cavernous angioma of the brain
Embolic and/or hemorrhagic stroke

Radiography

Findings

No specific findings related to DAI can be made using conventional radiography; however, other signs of head trauma can be appreciated, such as facial bone fractures or fluid levels within the paranasal sinuses.

Degree of Confidence

The degree of confidence is low, since conventional radiography cannot demonstrate subtle soft-tissue changes. While radiographs can clearly demonstrate skull fracture, this is not helpful in DAI, since DAI is rarely associated with skull fracture.

False Positives/Negatives

Many false negatives are possible, since a negative skull radiograph in no way excludes a parenchymal brain injury.

Computed Tomography

Findings

Among patients eventually proven to have DAI, 50-80% demonstrate a normal CT scan upon presentation. Delayed CT scanning may be helpful in demonstrating edema or atrophy, which are later findings. Small petechial hemorrhages, located at the gray-white matter junction, as well as in the corpus callosum and brainstem, are characteristic of CT-scan findings in the acute setting.

The following CT-scan criteria have been suggested by Wang and colleagues² :

• One or more small intraparenchymal hemorrhages less than 2 cm in diameter, located in the cerebral hemispheres
• Intraventricular hemorrhage
• Hemorrhage in the corpus callosum
• Small focal areas of hemorrhage less than 2 cm in diameter, adjacent to the third ventricle
• Brainstem hemorrhage

One may also observe small focal areas of low density on CT scans; these correspond to areas of edema occurring where shearing injury took place.

MRI is more sensitive in the detection of subtle soft-tissue abnormalities; however, CT scanning is more available and practical in the current medical environment and is therefore, according to Teasdale, the "mainstay of acute investigation of head injury."³

Degree of Confidence

The degree of confidence in CT scanning is moderate, since the only finding may be petechial hemorrhage, and fewer than 20% of patients with DAI demonstrate this finding on CT scanning alone. When petechial hemorrhages are observed with the appropriate clinical findings, the sensitivity of CT scanning in the detection of DAI is high.

False Positives/Negatives

As with conventional radiographs, frequent false negatives are possible, since normal CT-scan findings are common in patients with DAI.

Magnetic Resonance Imaging

Findings

Recommended sequences include T1-weighted, T2-weighted, T2 – gradient-echo, proton density – weighted, and diffusion-weighted images.

• T1-weighted images are helpful for anatomic localization; however, nonhemorrhagic lesions may be isointense to surrounding tissue. Hemorrhagic lesions appear hyperintense on T1-weighted images. Nonhemorrhagic lesions appear hyperintense on T2-weighted sequences. Diffusion-weighted sequences can reveal hyperintensities in areas of axonal injury.
• Gradient-echo sequences are particularly useful in demonstrating the paramagnetic effects of petechial hemorrhages. Gradient-echo imaging can often demonstrate signal abnormality in areas that appear normal in T1- and T2-weighted spin-echo sequences. For this reason, gradient-echo imaging has become a mainstay of MRI exams for patients with suggested shearing-type injuries. The abnormal signal on gradient-echo images can persist for many years after the injury.
• The most common MRI finding is the presence of multifocal areas of abnormal signal (bright on T2-weighted images) at the white matter in the temporal or parietal corticomedullary junction or in the splenium of the corpus callosum.
• Other areas that frequently are abnormal include the dorsolateral rostral midbrain and the corona radiata (see DAI stages in Anatomy).
• Eventually, nonspecific atrophic changes are observed.

One area of research has been magnetization transfer imaging. Studies have reported that the magnetic transfer ratio has shown promise in identifying areas of injury not visible on the above MRI pulse sequences. This may allow the radiologist to appreciate a truer representation of the degree of microscopic injury. Studies have indicated that MRI can play a role in predicting the length of coma in DAI patients. The volume of white-matter lesions has been correlated to the degree of injury, as measured by MRI. MRI has also been used to quantify cerebral blood flow in damaged areas of the brain, thus predicting injury severity.

Degree of Confidence

The degree of confidence is high, since abnormal signal in the characteristic locations, discovered in the clinical setting of recent trauma, leaves little doubt about the diagnosis of DAI.

Multiple sclerosis (MS) is a progressive neurologic disorder that can involve multiple foci of white-matter signal abnormality on MRI; however, MS lesions typically are oval or oblong and are oriented in a direction perpendicular to the border of the lateral ventricles (Dawson fingers). In addition, MS lesions may involve the spinal cord, a finding not associated with DAI, and the clinical course of MS is dramatically different from that of DAI.

Nuclear Imaging

Findings

Nuclear medicine currently has no role in the routine diagnostic workup of patients with possible DAI; however, studies have suggested that iodine-123 single-photon emission CT (SPECT) imaging demonstrates areas of hypoperfusion in areas of known injury and reveals additional areas of injury not visualized with MRI.

Intervention

Medicolegal Pitfalls

• False negatives are common with CT scans. In fact, CT-scan findings frequently are normal or almost normal on initial presentation (see Image 5). For this reason, when CT-scan findings are negative and DAI is suggested clinically, MRI may be performed, since this modality can demonstrate lesions not observed through CT scanning.
• False negatives may occur with MRI if only routine sequences are performed. A sequence (such as gradient echo) that accentuates the susceptibility artifact arising from blood products must be performed in order to recognize small petechial hemorrhages.

Multimedia

Media file 1: Noncontrast computed tomography (CT) scan of a trauma patient demonstrates multiple petechial hemorrhages (arrows) consistent with diffuse axonal injury. Note that the hemorrhages are characteristically located at the gray-white matter interface.

Media file 2: Magnetic resonance imaging (MRI) diffusion sequence demonstrating multiple foci of abnormal increased signal at the gray-white matter junction (arrow) and within the corpus callosum in a patient with diffuse axonal injury

Media file 3: Gradient-echo axial magnetic resonance image demonstrating numerous small foci of diminished signal consistent with the paramagnetic effect of the hemoglobin content of many acute hemorrhages

Media file 4: Fluid-attenuated inversion recovery sequence demonstrating edema within the corpus callosum (arrow) secondary to traumatic shearing injury. Note that other areas of edema are observed in this patient with diffuse axonal injury.

Media file 5: Noncontrast axial computed tomography (CT) scan demonstrates why magnetic resonance imaging (MRI) is the study of choice in diagnosing diffuse axonal injury. This CT scan appears normal, although on closer examination, punctate hypodensities can be observed in the right frontal and left parietal white matter.

References

1. Holbourn AHS. Mechanics of head injuries. Lancet. 1943;2:438-41.

2. Wang H, Duan G, Zhang J, et al. Clinical studies on diffuse axonal injury in patients with severe closed head injury. Chin Med J (Engl). Jan 1998;111(1):59-62. [Medline].

3. Teasdale GM. Head injury. J Neurol Neurosurg Psychiatry. May 1995;58(5):526-39. [Medline].

4. Adams JH, Jennett B, McLellan DR, et al. The neuropathology of the vegetative state after head injury. J Clin Pathol. Nov 1999;52(11):804-6. [Medline]. [Full Text].

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8. Gentry LR, Godersky JC, Thompson B, et al. Prospective comparative study of intermediate-field MR and CT in the evaluation of closed head trauma. AJR Am J Roentgenol. Mar 1988;150(3):673-82. [Medline].

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10. Gleckman AM, Bell MD, Evans RJ, et al. Diffuse axonal injury in infants with nonaccidental craniocerebral trauma: enhanced detection by beta-amyloid precursor protein immunohistochemical staining. Arch Pathol Lab Med. Feb 1999;123(2):146-51. [Medline].

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14. Osborn AG. Diagnostic Neuroradiology. St Louis, Mo: Mosby-Year Book; 1994:212-5.

15. Wilson JT, Hadley DM, Wiedmann KD, et al. Neuropsychological consequences of two patterns of brain damage shown by MRI in survivors of severe head injury. J Neurol Neurosurg Psychiatry. Sep 1995;59(3):328-31. [Medline].

16. Yamamoto T, Koeda T, Ishii S, et al. A patient with cerebral palsy whose mother had a traffic accident during pregnancy: a diffuse axonal injury?. Brain Dev. Jul 1999;21(5):334-6. [Medline].

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Keywords

DAI, axonal shear injury, axonal shear-strain injury, traumatic brain injuries

Contributor Information and Disclosures

Author

Jeffrey R Wasserman, DO, Staff Physician, Department of Diagnostic Radiology, Medical College of Pennsylvania-Hahnemann University Hospital
Jeffrey R Wasserman, DO is a member of the following medical societies: American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Koenigsberg, DO, MSc, FAOCR, Director of Neuroradiology, Professor, Department of Radiology, Drexel University College of Medicine
Robert A Koenigsberg, DO, MSc, FAOCR is a member of the following medical societies: American Osteopathic Association, American Society of Interventional & Therapeutic Neuroradiology, American Society of Neuroradiology, and Radiological Society of North America
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey L Creasy, MD, Associate Professor, Associate Section Head, Division of Neuroradiology, Director, Neuroradiology Fellowship, Department of Radiology, Vanderbilt University
Jeffrey L Creasy, MD is a member of the following medical societies: American College of Radiology, American Society of Neuroradiology, and Radiological Society of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

Robert L DeLaPaz, MD, Director, Professor, Department of Radiology, Division of Neuroradiology, Columbia University
Robert L DeLaPaz, MD is a member of the following medical societies: American Society of Neuroradiology, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

James G Smirniotopoulos, MD, Professor of Radiology, Neurology, and Biomedical Informatics, Chairman, Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences
James G Smirniotopoulos, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, American Society of Head and Neck Radiology, American Society of Neuroradiology, American Society of Pediatric Neuroradiology, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

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