What is the treatment for acute hemorrhagic leukoencephalitis?

Treatment for Acute Hemorrhagic Leukoencephalitis

High-dose intravenous corticosteroids followed by plasma exchange is the recommended first-line treatment for acute hemorrhagic leukoencephalitis (AHLE), though mortality remains high despite aggressive therapy. 1

Initial Management

• Immediate high-dose intravenous methylprednisolone (1 g intravenously daily for at least 3-5 days) should be administered as soon as AHLE is suspected, even before definitive diagnosis 1
• Plasma exchange should be considered early, particularly in patients who respond poorly to corticosteroids 1
• If herpes simplex virus (HSV) infection is suspected or cannot be ruled out, intravenous acyclovir (10-15 mg/kg every 8 hours) should be administered empirically 1, 2
• Patients with declining consciousness require urgent ICU assessment for airway protection, ventilatory support, and management of raised intracranial pressure 1

Diagnostic Approach

• Neuroimaging with MRI is essential and should be performed immediately to identify characteristic hemorrhagic white matter lesions 1, 3
• Lumbar puncture for CSF analysis is critical to exclude infectious causes and support diagnosis 1, 4
• Brain biopsy may be necessary for definitive diagnosis in unclear cases, revealing inflammatory demyelination and hemorrhagic foci 3

Treatment Algorithm

1. First-line therapy:

   • High-dose IV methylprednisolone (1 g/day for 3-5 days) 1
   • Continue aggressive supportive care including airway management and ICP control 1

2. If inadequate response within 48-72 hours:

   • Initiate plasma exchange (typically 5-7 exchanges) 1, 5
   • Consider adding cyclophosphamide, though evidence is limited 1

3. Supportive measures:

   • Manage cerebral edema with mannitol or hypertonic saline 4, 3
   • Seizure prophylaxis with antiepileptic medications 4
   • Maintain appropriate cerebral perfusion pressure 1

Special Considerations

• AHLE is often considered a hyperacute form of acute disseminated encephalomyelitis (ADEM) but with much higher mortality 6, 3
• In cases with suspected viral triggers (particularly HSV), acyclovir should be administered at 10-15 mg/kg every 8 hours for at least 14 days 1, 2
• Unlike typical ADEM, AHLE can progress rapidly to brain herniation and death within days despite aggressive treatment 4, 3

Prognosis and Monitoring

• AHLE has a very poor prognosis with mortality rates exceeding 70% in most series 3
• Repeat neuroimaging is essential to monitor disease progression and development of complications such as herniation 4, 3
• The few survivors often have significant residual neurological deficits 5, 3

Emerging Therapies

• Intravenous immunoglobulin (IVIG) has been used in some cases, though evidence for efficacy is limited 5, 3
• Combined immunosuppressive approaches (steroids plus plasma exchange plus cyclophosphamide) have been attempted in severe cases 5
• Early diagnosis and aggressive immunomodulatory treatment offer the best chance for survival 2, 3