What is the treatment for meningoencephalitis?

Treatment of Meningoencephalitis

Immediately initiate intravenous acyclovir (10 mg/kg every 8 hours in adults with normal renal function; 20 mg/kg every 8 hours in neonates) in all patients with suspected meningoencephalitis as soon as possible, pending diagnostic results, because early treatment of herpes simplex encephalitis dramatically reduces mortality and serious sequelae. 1, 2

Empirical Treatment Approach

Immediate Antimicrobial Therapy

• Start IV acyclovir immediately upon suspicion of meningoencephalitis, before any diagnostic confirmation, as this is the single most critical intervention for reducing morbidity and mortality 1, 3
• The FDA-approved dosing is 10 mg/kg IV every 8 hours in adults and children with normal renal function, and 20 mg/kg IV every 8 hours in neonates 2
• Never delay acyclovir while awaiting diagnostic confirmation, as HSV encephalitis has devastating consequences if untreated 3

Additional Empirical Coverage

• Add appropriate therapy for bacterial meningitis if clinically indicated (altered mental status with meningeal signs and CSF pleocytosis) 1
• Add doxycycline if there is clinical suspicion of rickettsial or ehrlichial infection during appropriate season 1
• Consider epidemiologic and clinical factors when determining additional empirical antimicrobial agents 1

Diagnostic Workup During Treatment

Essential Testing

• Perform lumbar puncture with CSF analysis including cell count, protein, glucose, and PCR for HSV-1, HSV-2, VZV, enterovirus, and other relevant viruses 1, 3
• Obtain MRI with contrast of brain (and spinal cord if indicated) within 48 hours 3
• CSF PCR is the gold standard for confirming viral meningoencephalitis 1

Important Caveat on PCR Testing

• A negative initial CSF PCR does not exclude HSV encephalitis, particularly if obtained very early in disease course 1
• If clinical suspicion remains high for HSV encephalitis with temporal lobe lesions on neuroimaging, repeat CSF PCR 3-7 days later on a second specimen 1
• Only a negative repeat PCR may allow safe discontinuation of acyclovir 1

Duration and Discontinuation of Empirical Acyclovir

When to Continue Acyclovir

• Continue acyclovir until CSF PCR results return negative for HSV 3
• In confirmed HSV encephalitis, mortality at 18 months remains 28% even with treatment, emphasizing the importance of full treatment course 1
• Predictors of adverse outcome include age >30 years, Glasgow coma score <6, and duration of symptoms >4 days before starting acyclovir 1

When to Stop Acyclovir

• Discontinue acyclovir if CSF PCR is negative for HSV/VZV and an alternative diagnosis is established 1
• Stop antibiotics once viral diagnosis is confirmed and prioritize expediting discharge 1
• Common pitfall: Many patients receive unnecessary prolonged acyclovir courses when viral meningitis (not encephalitis) is the diagnosis 4, 5

Distinguishing Meningitis from Encephalitis

Key Clinical Distinction

• Altered mental status (changes in personality, behavior, cognition, or consciousness level) is the critical distinguishing feature of encephalitis versus meningitis 1, 4
• Pure viral meningitis (without encephalitis features) typically does not require acyclovir, as it is usually a benign self-limited illness 1, 6
• If any suggestions of encephalitis develop, immediately give IV acyclovir for suspected HSV encephalitis 1

Treatment for Viral Meningitis Alone

• No proven benefit exists for acyclovir or valacyclovir in HSV or VZV meningitis without encephalitis features 1
• Treatment should be supportive with analgesia and fluids 1
• The risks of drug side effects and prolonged hospitalization should be weighed against lack of efficacy evidence 1

Etiology-Specific Treatment

Herpes Simplex Virus Encephalitis

• Acyclovir is the treatment of choice for HSV encephalitis 1, 2
• Standard treatment duration is 10 days for confirmed HSV encephalitis 2
• Mortality decreased to 8% in patients treated early (within 4 days of symptom onset) 1

Varicella Zoster Virus

• Although no established efficacy data exist for VZV-associated encephalitis, treatment with acyclovir is recommended based on case reports 1
• Use same dosing as for HSV encephalitis 1

Other Viral Causes

• No specific antiviral therapy exists for most other viral causes of encephalitis (West Nile virus, enterovirus, influenza) 1
• Ribavirin for West Nile virus showed potentially deleterious effects and is not recommended 1
• IFN-α for West Nile virus encephalitis showed inconclusive results and is not routinely recommended 1

Acute Disseminated Encephalomyelitis (ADEM)

• High-dose IV methylprednisolone (1 g daily for at least 3-5 days) is recommended once infection is ruled out 1, 3
• Consider plasma exchange in patients who respond poorly to corticosteroids 1
• Follow with oral corticosteroid taper over minimum 4-6 weeks to prevent relapse 3

Special Populations

Immunocompromised Patients

• Enteroviral meningoencephalitis in agammaglobulinemia should be treated with high-dose IVIG with measurable antibody to the infecting virus, maintaining IgG trough levels >1000 mg/dL 1
• Consider intraventricular IgG in refractory cases 1

Cryptococcal Meningoencephalitis

• This requires amphotericin B-based induction therapy, not acyclovir 1
• Liposomal amphotericin B (3-4 mg/kg/day) plus flucytosine is preferred 1

Critical Pitfalls to Avoid

• Never delay acyclovir while awaiting diagnostic studies—start immediately upon clinical suspicion 1, 3
• Do not rely on a single negative CSF PCR to exclude HSV encephalitis if clinical suspicion remains high 1
• Avoid premature discontinuation of acyclovir before CSF PCR results are available 3
• Do not use acyclovir for isolated viral meningitis without encephalitis features, as this exposes patients to unnecessary nephrotoxicity and neurotoxicity 1, 4
• Recognize that altered mental status is essential for diagnosing encephalitis—fever and headache alone suggest meningitis 1, 4