Treatment of Encephalitis
Immediately initiate intravenous acyclovir 10 mg/kg every 8 hours for all patients with suspected encephalitis, without waiting for diagnostic confirmation, as this dramatically improves outcomes in herpes simplex encephalitis (HSE)—the most important treatable cause. 1, 2, 3
Immediate Empiric Antiviral Therapy
Start IV acyclovir 10 mg/kg every 8 hours immediately upon suspicion of encephalitis, before any diagnostic test results return, given the life-threatening nature of HSE and the remarkable safety profile of acyclovir 1, 2, 4
Continue treatment for 14-21 days for confirmed HSE 5
Do not delay treatment even if lumbar puncture or imaging cannot be performed immediately—the mortality of untreated HSE reaches 70%, while early acyclovir reduces this dramatically 2, 4
Diagnostic Workup (Performed Concurrently with Treatment)
Lumbar Puncture Priority
Perform LP as soon as possible after hospital admission unless contraindications exist (signs of raised intracranial pressure with brain shift) 6
If CT is needed first due to concern for raised ICP, perform imaging emergently, then reassess LP safety on a case-by-case basis 6
In anticoagulated patients, reverse anticoagulation adequately before LP (protamine for heparin; vitamin K, prothrombin complex concentrate, or FFP for warfarin) 6
Essential CSF Studies
HSV-1 and HSV-2 PCR (diagnostic method of choice with very high sensitivity/specificity) 2, 4, 5
VZV PCR and enterovirus PCR 6
CSF protein, glucose, and cell count with differential 2
Additional testing in immunocompromised patients: EBV PCR, CMV PCR, cryptococcal antigen, acid-fast bacillus staining, toxoplasma antibodies, syphilis serology 6
Imaging
MRI is preferred over CT and should be performed as soon as possible (either before LP if no contraindications, or immediately after) 6, 2
MRI may show characteristic temporal lobe involvement in HSE or hippocampal changes in autoimmune encephalitis 6
Pathogen-Specific Treatment Adjustments
Herpes Simplex Virus (HSV)
Continue IV acyclovir 10 mg/kg every 8 hours for 14-21 days 1, 5
In immunocompromised patients, viral clearance may be harder and prolonged treatment may be needed 6
After completion, repeat CSF PCR can confirm elimination of replicating virus 5
Varicella-Zoster Virus (VZV)
IV acyclovir may be effective, though evidence is less robust than for HSV 2
Dose: 10 mg/kg every 8 hours 1
Cytomegalovirus (CMV)
Ganciclovir, valganciclovir, foscarnet, or cidofovir based on open-label studies 6
Most relevant in immunocompromised patients 6
Enterovirus
- Pleconaril may be considered, though evidence is limited (Class IV) 2
Autoimmune Encephalitis Recognition and Treatment
When to Suspect Autoimmune Etiology
Subacute presentation with prominent psychiatric features, movement disorders (orofacial dyskinesia, choreoathetosis, faciobrachial dystonia), intractable seizures, or hyponatremia 6
These patients have poor outcomes if untreated, so early recognition is critical 6
Antibody Testing
Request VGKC-complex antibodies and NMDA receptor antibodies in serum when clinical features suggest autoimmune encephalitis 6
CSF antibodies may not always be detectable even when serum is positive 6
Immunotherapy for Confirmed Autoimmune Encephalitis
High-dose IV methylprednisolone (1g daily for 3-5 days) as initial treatment 7
IV immunoglobulin (0.4 g/kg/day) in conjunction with steroids—combination therapy is more effective than monotherapy 6, 7
Plasma exchange if response to steroids and IVIG is suboptimal 7
For refractory cases: rituximab or cyclophosphamide 7
Screen all patients with proven antibody-mediated encephalitis for underlying neoplasm (especially thymoma or small cell lung cancer) 6
Tumor removal combined with early immunosuppression improves outcomes 6
Critical Supportive Care Measures
Renal Protection During Acyclovir Therapy
Ensure adequate hydration to prevent acyclovir crystal precipitation in renal tubules (maximum solubility 2.5 mg/mL) 1
Administer acyclovir by slow IV infusion only—never by bolus injection 1
Monitor renal function and adjust dosing based on creatinine clearance 1
Avoid concomitant nephrotoxic drugs when possible 1
Neurological Monitoring
Approximately 1% of patients on IV acyclovir develop encephalopathic changes (lethargy, confusion, seizures, coma) 1
Use acyclovir with caution in patients with underlying neurologic abnormalities, renal/hepatic dysfunction, or significant hypoxia 1
Ensure easy access to intensive care for management of seizures, raised intracranial pressure, or respiratory compromise 2
Surgical Intervention
- Decompressive surgery is indicated for impending uncal herniation or increased intracranial pressure refractory to medical management 2
Special Populations
Immunocompromised Patients
Treat in an HIV center if HIV-positive 6
Perform broader microbiological testing even if CSF is acellular, as immunocompromised patients often lack typical inflammatory response 6
May require prolonged acyclovir courses for HSV clearance 6
Elderly Patients
HSV encephalitis is more common in elderly than younger adults, making prompt consideration essential 6
Dose reduction may be required due to age-related renal impairment 1
Recognition is more difficult as stroke and systemic sepsis are common confounders 6
Common Pitfalls to Avoid
Never delay acyclovir while awaiting diagnostic confirmation—the window for effective treatment is narrow 2, 4
Do not rely on CSF pleocytosis to diagnose encephalitis in immunocompromised patients—CSF may be acellular despite active infection 6
Negative HSV PCR early in disease course does not exclude HSE—interpret in clinical context and consider repeat LP if suspicion remains high 5
Do not use serum HSV antibodies for acute diagnosis in adults—they are not useful 5
Corticosteroids are not generally effective for acute viral encephalitis and remain controversial, though they are essential for confirmed autoimmune encephalitis 2