What is the immediate concern and management for a patient with Diffuse Axonal Injury (DAI) presenting with anisocoria?

Anisocoria in Diffuse Axonal Injury

Anisocoria in a patient with DAI represents a sign of brain herniation requiring immediate osmotherapy with either mannitol 20% or hypertonic saline at 250 mOsm infused over 15-20 minutes. 1

Immediate Clinical Concern

Anisocoria in the context of DAI signals threatened or active brain herniation, which is a life-threatening emergency requiring immediate intervention. 1 While DAI itself typically does not cause elevated intracranial pressure in isolation, the presence of anisocoria indicates a critical change suggesting either:

• Concurrent mass lesions (traumatic subarachnoid hemorrhage, subdural hematoma, or intraparenchymal hemorrhage frequently co-occur with DAI) 2
• Secondary brain injury with developing intracranial hypertension 3
• Brainstem compression from herniation 2

Immediate Management Algorithm

First-Line Treatment: Osmotherapy

Administer osmotherapy immediately upon recognition of anisocoria or other herniation signs (mydriasis, neurological deterioration not attributable to systemic causes). 1

Dosing options (equivalent efficacy at equiosmotic doses):

• Mannitol 20% at 250 mOsm infused over 15-20 minutes 1
• Hypertonic saline at 250 mOsm infused over 15-20 minutes 1

Mechanism and timing: Osmotherapy creates an osmotic gradient across the blood-brain barrier, reducing ICP with maximum effect at 10-15 minutes and duration of 2-4 hours, restoring cerebral blood flow. 1 Of available ICP-lowering therapies (mannitol, external ventricular drainage, hyperventilation), only mannitol was associated with improved cerebral oxygenation. 1

Critical Monitoring Requirements

Side effect management differs between agents:

• Mannitol: Causes osmotic diuresis requiring volume compensation; monitor fluid balance 1
• Hypertonic saline: Risk of hypernatremia and hyperchloremia; monitor sodium and chloride levels 1

Cerebral Perfusion Pressure Management

Target CPP 60-70 mmHg while maintaining ICP <20 mmHg. 1

• CPP <60 mmHg is associated with poor outcomes 1
• CPP >90 mmHg worsens outcomes due to aggravation of vasogenic cerebral edema 1
• Maintain systolic blood pressure >110 mmHg to ensure adequate cerebral perfusion 3

Ventilation Management

Control ventilation through intubation and mechanical ventilation with end-tidal CO2 monitoring. 3

Avoid prolonged hypocapnia: Severe and prolonged hypocapnia (PaCO2 25 mmHg for 5 days) worsens neurological outcomes compared to normocapnia (35 mmHg). 1 Hypocapnia exacerbates secondary ischemic lesions by decreasing cerebral blood flow and increasing oxygen extraction. 1

Diagnostic Considerations

Obtain urgent neuroimaging if not already performed:

• Non-contrast CT is first-line to identify mass lesions requiring surgical intervention 4, 3
• CT limitations: Misses microhemorrhages in 90% of DAI cases as most lesions lack macroscopic hemorrhage 4
• MRI with T2-weighted GRE and susceptibility-weighted imaging* is 3-6 times more sensitive for detecting hemorrhagic axonal injuries 4, 2

Critical Pitfalls to Avoid

Do not assume isolated DAI: DAI rarely occurs in isolation; actively search for concurrent traumatic subarachnoid hemorrhage, skull fractures, intraparenchymal hemorrhage, or acute subdural hematoma. 2

Do not use prophylactic osmotherapy: Prophylactic hypertonic saline in patients without evidence of intracranial hypertension is not superior to crystalloids. 1 Osmotherapy is indicated only for threatened herniation or documented elevated ICP.

Avoid 4% albumin: In severe TBI patients, 4% albumin solution increases mortality compared to 0.9% saline (24.5% vs 15.1%, RR 1.62). 1

ICP monitoring considerations: While pure DAI without mass lesions typically does not cause elevated ICP (mean ICP 11.7 mmHg with 89.7% of readings ≤20 mmHg), 5 the presence of anisocoria suggests either concurrent pathology or secondary injury requiring ICP monitoring if GCS ≤8. 5

Prognostic Implications

The presence of dorsolateral brainstem lesions (DAI Grade III) is associated with poor outcomes and highest mortality. 3, 2 Anisocoria suggesting brainstem involvement warrants early multidisciplinary case review and communication with regional neuroscience centers. 3