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Diffuse Axonal Injury

Fassil B. Mesfin; Nishant Gupta; Angela Hays Shapshak; Roger S. Taylor.

Author Information
Last Update: May 2, 2022.

Continuing Education Activity

Diffuse axonal injury (DAI) is a type of traumatic brain injury (TBI) that results from a blunt
injury to the brain. In the United States, traumatic brain injury is a leading cause of death and
disability among children and young adults. The Center for Disease Control and Prevention
(CDC) estimates that there are over 1.5 million reported cases of traumatic brain injury every
year in the United States. Traumatic brain injury is classified as mild, moderate, and severe based
on the Glasgow coma scale (GCS). Traumatic brain injury patients with GCS of 13 to 15 are
classified to be mild, which includes the majority of traumatic brain injury patients. Patients with
a GCS of nine to 12 are considered to have a moderate traumatic brain injury, while patients with
a GCS below eight are classified as having a severe traumatic brain injury. This activity reviews
the workup of diffuse axonal injury and the role of health professionals working together to
managing this condition.

Objectives:

Outline the Adams classification for axonal injury.

Review the management of axonal injuries.

Describe the presentation of axonal injury.

Outline the workup of diffuse axonal injury and the role of health professionals working
together to manage this condition.

Access free multiple choice questions on this topic.

Introduction
Diffuse axonal injury (DAI) is a type of traumatic brain injury (TBI) that results from a blunt
injury to the brain.[1] In the United States, traumatic brain injury is a leading cause of death and
disability among children and young adults. The Center for Disease Control and Prevention
(CDC) estimates that there are over 1.5 million reported cases of traumatic brain injury every
year in the United States. Traumatic brain injury is classified as mild, moderate, and severe based
on the Glasgow coma scale (GCS). Traumatic brain injury patients with GCS of 13 to 15 are
classified to be mild, which includes the majority of traumatic brain injury patients. Patients with
a GCS of nine to 12 are considered to have a moderate traumatic brain injury, while patients with
a GCS below eight are classified as having a severe traumatic brain injury.

The GCS measures the following three functions:

1. Eye Opening (E): 4-spontaneous, 3-to voice, 2-to pain, 1-none

2. Verbal Response (V): 5-normal conversation, 4-oriented conversation, 3-words, but not
coherent, 2-no words, only sounds, 1-none

3. Motor Response (M): 6-normal, 5-localized to pain, 4-withdraws to pain, 3-decorticate

posture, 2-decerebrate

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Diffuse axonal injury (DAI) primarily affects the white matter tracts in the brain. Clinically,
patients with DAI can present in a spectrum of neurological dysfunction. This can range from
clinically insignificant to a comatose state. However, most patients with DAI are identified to be
severe and commonly have a GCS of less than 8. A diffuse axonal injury is a clinical diagnosis.

Etiology
The most common etiology of diffuse axonal injury involves high-speed motor vehicle accidents.
[2] The most common mechanism involves an accelerating and decelerating motion that leads to
shearing forces to the white matter tracts of the brain. This leads to microscopic and gross
damage to the axons in the brain at the junction of the gray and white matter. Diffuse axonal
injury commonly affects white matter tracts involved in the corpus callosum and brainstem.
Interestingly, there is no association between diffuse axonal injury and underlying skull fractures.

Epidemiology
The true incidence of DAI is unknown. However, it is estimated that roughly 10% of all patients
with TBI admitted to the hospital will have some degree of DAI.[3] Of the patients with DIA, it
is estimated that roughly 25% will result in death. This statistic may be underestimated as
patients with subdural hematomas, epidural hematomas, and other forms of TBI will not carry a
true diagnosis of DAI. Postmortem studies have shown that patients with severe TBI have a
significant incidence of diffuse axonal injury.

Pathophysiology
The primary insults of diffuse axonal injury lead to disconnection or malfunction of neuron's
interconnection.[4] This affects numerous functional areas of the brain. Usually, patients with
diffuse axonal injury present with bilateral neurological examination deficits frequently affecting
the frontal and temporal white matter, corpus callosum, and brainstem. The Adams classification
of diffuse axonal injury utilizes pathophysiological lesions in the white matter tracts and clinical
presentation.

The Adams Diffuse Axonal Injury Classification

Grade 1: A mild diffuse axonal injury with microscopic white matter changes in the
cerebral cortex, corpus callosum, and brainstem

Grade 2: A moderate diffuse axonal injury with gross focal lesions in the corpus callosum

Grade 3: A severe diffuse axonal injury with finding as Grade 2 and additional focal
lesions in the brainstem

Histopathology
Axonal portions of neurons have a mechanical disruption of cytoskeletons resulting in
proteolysis, swelling, and other microscopic and molecular changes to the neuronal structure.

History and Physical

DAI is a clinical diagnosis. Typically, DAI is considered in patients with a GCS of less than 8 for
over six hours. The clinical presentation of patients with diffuse axonal injury relates to the
severity of a diffuse axonal injury. For example, patients with mild diffuse axonal injury present
with signs and symptoms that reflect a concussive disorder. These symptoms most commonly
include a headache. The other post-concussive symptoms can include dizziness, nausea,
vomiting, and fatigue. However, patients with a severe diffuse axonal injury may also present
with a loss of consciousness and remain in a persistent vegetative state. A very small number of

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those patients with severe diffuse axonal injury will regain consciousness in the first year after
the injury.

Other common neurological manifestations include dysautonomia. Dysautonomic

symptoms commonly include tachycardia, tachypnea, diaphoresis, vasoplegia, hyperthermia,
abnormal muscle tone, and posturing.

Evaluation
In general, diffuse axonal injury is a severe form of traumatic brain injury.[5] Therefore, the
implementation of an advanced trauma life support protocol is a standard of care for all head-
injured patients.

A definitive diagnosis of diffuse axonal injury can be made in the postmortem pathologic
examination of brain tissue. However, in clinical practice, a diagnosis of diffuse axonal injury is
made by implementing clinical information and radiographic findings. Understanding the
mechanism of head injury facilitates a differential diagnosis of DAI. Patients who experience
rotational or acceleration-deceleration closed head injury should be suspected to have DAI.
Generally, DAI is diagnosed after a traumatic brain injury with GCS less than 8 for more than six
consecutive hours.

Radiographically, computed tomography (CT) head findings of small punctate hemorrhages to

white matter tracts can indicate diffuse axonal injury in the setting of an appropriate clinical
presentation. Overall, CT head has a low yield in detecting diffuse axonal injury-related injuries.
Currently, magnetic resonance imaging (MRI), specifically diffuse tensor imaging (DTI), is the
imaging modality of choice for the diagnosis of diffuse axonal injury. A recent report suggests
that acute gradient-recalled echo (GRD) MRI will enhance the detection of axonal injury in grade
3 diffuse axonal injury patients, suggesting that it is most likely a better diagnostic tool.

It should be of note that DAI should be strongly considered in patients that fail to improve after
receiving surgical evacuation of subdural or epidural hematomas. Conversely, if patients
drastically improve after surgical evacuation of a subdural or epidural hematoma, DAI may not
be present.

Currently, there are no laboratory tests for the diagnosis of DAI.[6] However, there is current
research on identifying molecular markers in the serum of traumatic brain injury patients to help
aid the diagnosis of DAI.

Treatment / Management
Treatment of patients with diffuse axonal injury is geared toward the prevention of secondary
injuries and facilitating rehabilitation. It appears to be the secondary injuries that lead to
increased mortality. These can include hypoxia with coexistent hypotension, edema, and
intracranial hypertension. Therefore, prompt care to avoid hypotension, hypoxia, cerebral edema,
and elevated intracranial pressure (ICP) is advised.

Initial treatment priority in traumatic brain injury is focused on resuscitation. In a non-neuro

trauma center, trauma surgeons and emergency physicians may perform the initial resuscitation
and neurologic treatment to stabilize and transport the patient to a designated neurotrauma center
expeditiously. ICP monitoring is indicated in patients with a GCS of less than 8 after consultation
with neurosurgery. Other considerations for ICP monitoring include patients that cannot have
continual neurologic evaluations. These are typically in patients receiving general anesthesia,
opioid analgesia, sedation, and prolonged paralysis for other injuries. Cerebral oxygen saturation
monitoring can be used with ICP monitoring to assess the degree of oxygenation. Short-term,
usually seven days, anticonvulsant treatment can be used to prevent early post-traumatic
seizures. There is no evidence that this will prevent long-term post-traumatic seizures, however.

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There is emerging evidence that progesterone treatment in acute traumatic brain injury may
reduce morbidity and mortality. This cannot be routinely recommended at this time.

Overall, the goal of the treatment of patients with diffuse axonal injury is supportive care and
prevention of secondary injuries.

Differential Diagnosis

Subdural hematoma

Epidural hematoma

Subarachnoid hemorrhage

Various Intracerebral hemorrhage types

Ischemic and hemorrhagic cerebrovascular accident

Concussion/post-concussive syndrome

Hypoglycemia

Prognosis
Prognosis is considered to be poor in patients with severe DAI.

Complications
Dysautonomia is frequently encountered. Unfortunately, no definitive treatment exists, and
supportive care is advised.[7][8][9]

Postoperative and Rehabilitation Care

Postoperative care, if operative intervention is pursued, typically is aimed at reducing ICP and
improving cerebral blood flow.

Patients and families should expect prolonged rehabilitative therapies after severe DAI. This can
include physical, occupational, speech, and other psychosocial therapies.

Consultations
Typically neurosurgery, neurology, trauma surgery, and intensive care can help guide therapies.

Pearls and Other Issues

A diffuse axonal injury is a type of severe traumatic brain injury that affects patients and their
families. Patients with diffuse axonal injury have a range of multiple neurological deficits that
affect the physical and mental status of the patient. These changes usually compromise social
reintegration, return to productivity, and quality of life of patients and their families. For most
patients and families, the clinical status of patients with diffuse axonal injury will continue to
persist for a minimum of two years. Then, most patients and families will achieve and accept a
new baseline. Recent epidemiological studies indicate that the outcomes of patients with diffuse
axonal injury are associated with the number of lesions identified through imaging. There are
emerging studies suggesting that during the acute phase of diffuse axonal injury, hypoxia, and
hypotension are associated with increased mortality. Therefore, it is important to continue
investigating the clinical, pathophysiological, and radiographic studies to advance the
management of patients with diffuse axonal injury.

Enhancing Healthcare Team Outcomes

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Patients with DAI often have a severe brain injury and are best managed by an interprofessional
team that includes a neurologist, neurosurgeon, physical and occupational therapist, speech
therapist, intensivist, internist, ICU nurses, neuroscience nurses, and rehabilitation nurses.
[10] Pharmacists review prescribed medications, including anticonvulsants, and check for drug-
drug interactions. Nurses monitor patients and inform the team about changes in status. Patients
with diffuse axonal injury have a range of multiple neurological deficits that affect the physical
and mental status of the patient. These changes usually compromise social reintegration, return to
productivity, and quality of life of patients and their families. For most patients and families, the
clinical status of patients with diffuse axonal injury will continue to persist for a minimum of two
years.[11]

The outcome for patients with DAI is generally poor. The recovery is long, and complete
recovery is usually not possible in cases of severe injury. For many, there is life long disability
with a poor quality of life.[12][13][14][Level 5]

Review Questions

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References
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