What is the optimal management approach for a patient with suspected diffuse axonal injury?

Management of Suspected Diffuse Axonal Injury

Patients with suspected diffuse axonal injury require immediate transfer to a specialized neurosurgical center with urgent non-contrast CT followed by MRI within 24 hours, aggressive physiological stabilization targeting systolic BP >110 mmHg and normocapnia, and early multidisciplinary rehabilitation planning. 1, 2

Immediate Triage and Transfer

Transfer all severe TBI patients with suspected DAI to a specialized center with neurosurgical facilities immediately. 1 Mortality rates are significantly lower in neurosurgical centers compared to non-specialized centers, even for patients who do not require neurosurgical procedures, due to accumulated expertise and availability of specialized monitoring. 1

• Pre-hospital management should be conducted by a medicalized team capable of airway management and hemodynamic stabilization. 1
• Do not delay transfer for extensive workup at non-specialized facilities. 1

Diagnostic Imaging Protocol

Initial CT Imaging

Perform non-contrast CT of the brain and cervical spine without delay upon arrival. 1, 2 This is a Grade 1+ recommendation despite CT detecting only 10% of DAI cases, as it remains essential for excluding surgical mass lesions and guiding immediate management. 2, 3

• Use inframillimetric sections reconstructed with thickness >1mm, visualized with double fenestration (CNS and bone windows). 1
• Consider CT angiography of supra-aortic and intracranial arteries in patients with risk factors for traumatic dissection. 1

MRI Imaging

Obtain MRI within 24 hours when CT is normal but unexplained neurological findings persist (Class I recommendation). 2, 4, 3 MRI detects DAI in approximately 27% of patients with normal CT and improves prediction of 3-month outcomes. 2, 3

The optimal MRI protocol includes: 2, 3

• Susceptibility-weighted imaging (SWI) - 3-6 times more sensitive than conventional sequences for hemorrhagic axonal injuries
• T2-weighted gradient-echo (GRE)* - detects microhemorrhages in acute, subacute, and chronic stages
• Diffusion-weighted imaging (DWI) - visualizes non-hemorrhagic axonal injuries
• Thin-slice 3D T1-weighted sequences and FLAIR T2 sequences

Critical caveat: Do not use gadolinium-based contrast agents routinely, as they are not necessary for conventional MRI in TBI (Class IIb recommendation). 3

Acute Physiological Management

Blood Pressure Management

Maintain systolic blood pressure >110 mmHg at all times. 1, 2, 4 This is a Grade 2+ recommendation from the American College of Cardiology. 2 Hypotension compounds secondary brain injury and adversely affects neurological outcomes. 1

• Use direct arterial blood pressure monitoring with the transducer at the level of the tragus (especially with head-up positioning). 1
• Reverse hypovolemia aggressively before transfer. 1
• Use isotonic crystalloid (0.9% saline) to maintain hydration while preventing volume overload. 1

Ventilation Management

Intubate and mechanically ventilate patients with severe DAI, targeting PaO2 ≥13 kPa and PaCO2 4.5-5.0 kPa. 1, 2, 4 This is a Grade 1+ recommendation. 1

• Monitor end-tidal CO2 continuously, maintaining EtCO2 between 30-35 mmHg prior to arterial blood gas confirmation. 1
• Avoid hypocapnia: PaCO2 <4.0 kPa causes cerebral vasoconstriction and increases brain ischemia risk. 1, 4
• Use minimum 5 cmH2O PEEP to prevent atelectasis; PEEP up to 10 cmH2O does not adversely affect cerebral perfusion. 1
• Only use hyperventilation (PaCO2 not less than 4 kPa) as a temporizing measure for impending uncal herniation, combined with mannitol (0.5 g/kg) or hypertonic saline (2 ml/kg of 3% saline). 1

Intracranial Pressure Management

Monitor ICP in patients with severe TBI (GCS <9), with intervention threshold typically at ICP >20 mmHg. 2, 4 This recommendation comes from the Neurocritical Care Society. 4

• Consider external ventricular drainage for persistent intracranial hypertension despite sedation and correction of secondary insults (Grade 2+ recommendation). 2
• Decompressive craniectomy may be considered for refractory intracranial hypertension in multidisciplinary discussion (Grade 2+ recommendation). 2

Sedation and Positioning

Position patients with 20-30° head-up tilt while maintaining spinal immobilization. 1

• Maintain continuous sedation and analgesia (preferably by infusion or target-controlled infusion if available). 1
• Use neuromuscular blockade as needed. 1
• Consider processed EEG monitors for titration of sedation. 1

Prognostic Assessment

DAI grading strongly correlates with outcomes: 2, 3

• Grade III DAI (dorsolateral brainstem lesions) is associated with poor outcomes and highest mortality
• Presence of both a contusion and >4 foci of hemorrhagic axonal injury on MRI is an independent prognostic predictor
• Location and extent of lesions correlate with clinical outcomes

Key prognostic factors in multivariate analysis: 5

• Dysautonomia (OR 4.17)
• Hyperglycemia ≥8 mmol/L (OR 3.84 for mortality, OR 5.55 for poor outcome)
• Subdural hematoma (OR 3.99)
• Glasgow Coma Scale <8 (OR 3.55 for poor outcome)
• DAI count ≥6 (OR 3.33 for poor outcome)

Important caveat: The number of microhemorrhages alone is not currently associated with injury severity or outcomes. 2, 3

Biomarkers

Do not use biomarkers in clinical routine to assess initial severity (Grade 2- recommendation). 1 While associations exist between neurological outcomes and biomarkers (S100b, NSE, UCH-L1, GFAP, MBP, tau protein), uncertainties remain regarding normal ranges and clinical utility. 1

Early Rehabilitation

Initiate physical therapy immediately to prevent joint contractures and muscle atrophy. 2, 4 This recommendation comes from the American Physical Therapy Association. 4

Specific interventions include: 2

• Proper positioning and frequent repositioning
• Range of motion exercises
• Splinting as needed
• Regular neurological assessments to detect clinical deterioration

Multidisciplinary Management

Conduct regular multidisciplinary case reviews for all patients with severe DAI. 2, 4, 3 Early communication with regional neuroscience centers is essential for patients with perceived devastating brain injury. 1, 2, 4

• Allow a period of physiological stabilization and observation (typically 72 hours minimum) before prognostic discussions to improve decision-making quality. 1
• Establish patient values and preferences early to guide end-of-life care planning if needed. 4
• Consider early palliative medicine consultation for elderly patients with severe injuries unlikely to be fully recoverable, as this improves outcomes, reduces mortality and length of stay, and improves family communication. 2
• Decouple conversations about neurological testing or withdrawal of life-sustaining treatment from organ donation discussions. 1

Follow-up Imaging

Obtain repeat imaging only with neurological deterioration, not routinely. 2, 4 Repeat CT is recommended for patients with epidural, subdural, and parenchymal hematomas, but may be less likely to alter management in patients with subarachnoid hemorrhage alone. 2

Common Pitfalls

• Do not rely on CT alone: 90% of DAI cases are missed on conventional CT because most lesions lack macroscopic hemorrhage. 2, 3
• Do not make early prognostic determinations: Allow adequate time for physiological stabilization before discussing long-term prognosis. 1
• Do not use routine hyperventilation: This causes cerebral vasoconstriction and worsens outcomes; reserve for impending herniation only. 1
• Do not permit hypotension or hypoxia: Even brief episodes compound secondary brain injury. 1