Diffuse Axonal Injury (DAI) 

Definition

Diffuse Axonal Injury (DAI) is a form of traumatic brain injury (TBI) characterized by widespread microscopic damage to axons in the cerebral hemispheres, corpus callosum, and brainstem, caused by rotational or acceleration–deceleration forces, often without a large focal lesion.

It is a major cause of prolonged coma, persistent vegetative state, and severe disability following head injury.

Epidemiology

• Accounts for ~40–50% of severe TBI
• Common in:
  • Road traffic accidents
  • High-velocity trauma
  • Falls from height
  • Assaults with rotational force
• Often seen in young adults

Mechanism of Injury 

Primary Injury (Immediate)

• Shearing forces due to:
  • Rapid acceleration–deceleration
  • Rotational movement of the head
• Differential movement between:
  • Grey matter (denser)
  • White matter (less dense)
• Leads to stretching and tearing of axons

Secondary Axonal Injury (Hours–Days)

• Disruption of axonal cytoskeleton:
  • Microtubules
  • Neurofilaments
• Axonal transport failure
• Calcium influx → mitochondrial dysfunction
• Axonal swelling → retraction bulbs
• Eventual axonal disconnection

# Key exam point: DAI is not truly “diffuse”, but multifocal, involving characteristic locations.

Pathology

Microscopic Features

• Axonal swelling
• Axonal bulbs (retraction balls)
• Myelin damage
• Seen best with:
  • β-amyloid precursor protein (β-APP) immunostaining

Gross Pathology

• Often normal or minimal findings
• Small petechial hemorrhages may be present

Common Anatomical Sites Involved

1. Parasagittal white matter
2. Corpus callosum (especially splenium)
3. Internal capsule
4. Brainstem (dorsolateral midbrain, pons)
5. Cerebellar peduncles

#Brainstem involvement → poor prognosis

Classification (Adams Classification )

Clinical Features

Immediate Presentation

• Loss of consciousness at the time of injury
• Coma lasting:
  • 6 hours (classic definition)
• No lucid interval

Neurological Findings

• Low GCS disproportionate to CT findings
• Decorticate or decerebrate posturing
• Abnormal pupillary responses (if brainstem involved)
• Autonomic instability (later)

Course

• Prolonged coma
• Persistent vegetative state or minimally conscious state
• Severe cognitive and behavioral deficits in survivors

—>Exam pearl: Severe coma with normal or near-normal CT → think DAI

Imaging

CT Scan (Initial)

• Often normal or subtle
• May show:
  • Small punctate hemorrhages
  • Loss of gray–white differentiation
• Poor sensitivity

MRI – Gold Standard

Best modality for diagnosis

MRI Findings

• T2 / FLAIR:
  • Hyperintense lesions in white matter
• Gradient Echo (GRE) / SWI:
  • Detects microhemorrhages (very sensitive)
• Diffusion-weighted imaging (DWI):
  • Restricted diffusion in acute axonal injury
• DTI (Diffusion Tensor Imaging):
  • Research tool
  • Demonstrates white matter tract disruption

—> Most sensitive sequence: SWI

Differential Diagnosis

• Hypoxic-ischemic brain injury
• Metabolic encephalopathy
• Central pontine myelinolysis
• Fat embolism syndrome
• Acute demyelinating disorders

Management of DAI

Core Principle

—> No specific treatment reverses axonal injury
Management is supportive and neuroprotective

Acute Management (ICU)

1. Airway and Ventilation

• Early intubation for GCS ≤8
• Avoid hypoxia (PaO₂ >60 mmHg)
• Avoid hypercapnia

2. Hemodynamic Optimization

• Maintain CPP ≥60–70 mmHg
• Avoid hypotension (SBP <90 mmHg worsens outcome)

3. ICP Management

• Head elevation 30°
• Adequate sedation and analgesia
• Osmotherapy (mannitol / hypertonic saline if ICP raised)
• Avoid routine hyperventilation

4. Sedation

• Propofol / midazolam
• Prevent agitation and secondary injury

5. Seizure Prophylaxis

• Levetiracetam or phenytoin (first 7 days)

6. Temperature Control

• Avoid fever
• Target normothermia

Role of Surgery

—> No role for decompressive surgery unless:

• Associated mass lesion
• Raised ICP refractory to medical therapy

Prognosis

Factors Affecting Outcome

• Duration of coma
• GCS on admission
• Brainstem involvement
• Age
• Associated hypoxia/hypotension

Outcome Spectrum

• Mild DAI → good recovery
• Severe DAI:
  • Persistent vegetative state
  • Severe disability
  • Death

—> Brainstem lesions = worst prognosis

Long-Term Sequelae

• Cognitive impairment
• Memory loss
• Attention deficits
• Behavioral changes
• Emotional lability
• Parkinsonism (rare, late)

#One-Liners

• DAI is caused by rotational acceleration–deceleration injury
• CT may be normal despite severe coma
• MRI (SWI) is most sensitive
• β-APP staining confirms axonal injury
• No focal mass lesion
• Management is supportive
• Brainstem involvement predicts poor outcome

Comparison: DAI vs Contusion

Key References

• Harrison’s Principles of Internal Medicine
• Adams & Victor’s Principles of Neurology
• Brain Trauma Foundation Guidelines
• Irwin & Rippe – Intensive Care Medicine
• Vincent – Critical Care