What is the treatment for Epstein-Barr Virus (EBV) encephalitis?

Treatment of Epstein-Barr Virus (EBV) Encephalitis

For EBV encephalitis, acyclovir is not recommended as first-line treatment, but rather a combination of corticosteroids and supportive care should be used, with consideration of antiviral therapy in severe cases. 1

Diagnostic Considerations

• EBV encephalitis should be considered in patients presenting with altered mental status, fever, and neurological symptoms, particularly in immunocompromised patients 2
• Diagnosis requires CSF examination with PCR testing for EBV, along with serology to determine acute infection versus reactivation 2
• MRI should be performed as soon as possible in all patients with suspected encephalitis 2
• CSF typically shows pleocytosis with mononuclear cell predominance 3

Treatment Algorithm

First-line Treatment

• According to the American Academy of Neurology, acyclovir has limited benefit for EBV encephalitis and is not routinely recommended 1
• The Infectious Diseases Society of America suggests that corticosteroids may be beneficial in selected patients with EBV-associated neurological complications 1
• Consider a course of corticosteroids (e.g., prednisolone 60-80 mg daily for 3-5 days) for the inflammatory component of the disease 2

For Immunocompromised Patients

• In immunocompromised patients, particularly post-transplant patients with EBV-related complications:
  • Rituximab 375 mg/m² once weekly until EBV DNA-emia negativity (typically 1-4 doses) is recommended 2
  • Reduction of immunosuppression should be combined with rituximab when possible 2
  • Consider EBV-specific cytotoxic T lymphocytes (CTL) if available 2

For Severe Cases

• In severe or refractory cases with neurological deterioration:
  • Consider antiviral therapy despite limited evidence 4
  • For CNS EBV disease post-transplant, options include rituximab ± chemotherapy, systemic or intrathecal rituximab monotherapy, anti-EBV T-cell therapy, or radiotherapy 2
  • In cases with significant cerebral edema, decompressive craniectomy may be life-saving 5, 6

Supportive Care

• Manage seizures appropriately with antiepileptic medications 7
• Monitor for and treat increased intracranial pressure 6
• Consider transfer to a specialist neuroscience unit for patients with falling level of consciousness or who fail to improve with therapy 2

Special Considerations

• In immunocompromised patients, the differential diagnosis is broader, and additional testing for CMV, HHV-6/7, toxoplasmosis, and cryptococcus should be considered 2
• Recent case reports suggest potential benefit of ganciclovir in some cases of EBV encephalitis, particularly those presenting with status epilepticus 8
• Some case reports have shown successful outcomes with combined therapy of corticosteroids and acyclovir, despite guidelines not recommending acyclovir 5, 4

Monitoring and Follow-up

• Consider repeating CSF examination to monitor viral clearance 4
• Patients should have access to assessment for rehabilitation, as neurological sequelae may persist 7
• Monitor for potential complications including seizures, raised intracranial pressure, and cognitive impairment 6

Common Pitfalls

• Delaying treatment in severe cases while awaiting confirmatory testing can lead to worse outcomes 9
• EBV encephalitis can sometimes mimic HSV encephalitis clinically and on EEG, leading to diagnostic confusion 3
• Normal initial neuroimaging does not exclude the diagnosis of encephalitis if clinical presentation is suggestive 6