Herpes Simplex Encephalitis
In this 25-year-old woman presenting with fever, confusion, lethargy, mild neck stiffness, and a CT scan showing low attenuation in the right temporoparietal region, herpes simplex encephalitis (HSE) is the most likely diagnosis.
Clinical Reasoning
The constellation of findings strongly points to HSE rather than the other options:
- Temporal lobe involvement is nearly pathognomonic for HSV-1 encephalitis, with bilateral temporal lobe abnormalities seen in >90% of laboratory-confirmed cases 1
- The classic triad of fever, altered mental status (confusion/lethargy), and temporal lobe abnormalities on imaging is characteristic of HSE 2, 1
- HSV-1 accounts for 25-40% of all sporadic encephalitis cases worldwide, making it the most common identified cause 1, 3
Why Not the Other Diagnoses?
Brain Abscess
- Brain abscesses typically present with more focal neurological deficits and a longer prodrome of weeks rather than 4 days 2
- The imaging pattern and clinical tempo do not fit 2
Pneumococcal Meningitis
- Pneumococcal meningitis would show more pronounced meningismus and typically does not produce focal temporal lobe lesions on CT 2
- The 4-day history with confusion suggests parenchymal involvement (encephalitis) rather than pure meningitis 2
Listeria Meningoencephalitis
- Listeria typically affects the brainstem (rhombencephalitis) rather than the temporal lobes 4, 5
- Listeria encephalitis usually presents with a biphasic course: flu-like prodrome followed by brainstem dysfunction 4
- When Listeria does cause encephalitis with RBCs in CSF (mimicking HSV), elevated CSF lactic acid distinguishes Listeria from HSV (elevated in Listeria, normal in HSV) 5
- The temporoparietal location makes Listeria much less likely 4, 5
Immediate Management Algorithm
1. Empiric Antiviral Therapy (Do Not Wait for Confirmation)
- Start IV acyclovir 10 mg/kg every 8 hours immediately without awaiting PCR results 2, 1, 3
- Early treatment is critical: mortality without acyclovir exceeds 70%, versus approximately 40% with treatment 6, 7
- Patients treated early (before coma) have 65% chance of normal recovery versus <30% if treatment is delayed 6
2. Diagnostic Workup
- Perform lumbar puncture for CSF HSV PCR (sensitivity 96-98%, specificity 95-99%) 1, 3
- Send CSF for cell count, protein, glucose, and bacterial culture to exclude bacterial meningitis 1
- Optimal timing for HSV PCR is days 2-10 of illness; false negatives can occur if sampled too early 1, 3
- Obtain MRI brain (preferred over CT): MRI has ~90% sensitivity within 48 hours versus CT's 25% sensitivity 2, 1
- Consider EEG: periodic lateralizing epileptiform discharges in temporal regions occur in ~80% of HSE cases 1
3. Duration of Therapy
- Continue IV acyclovir for 14-21 days in adults with confirmed HSE 1, 3, 7
- Adjust dose for renal impairment and maintain adequate hydration 1
Critical Pitfalls to Avoid
- Never delay acyclovir while awaiting imaging or PCR confirmation—this increases mortality and morbidity dramatically 1, 6
- Do not rely on a single negative HSV PCR to exclude HSE, especially if obtained early (<72 hours) or late in disease course 8, 3
- Do not use CT as the sole imaging modality—its poor sensitivity (25%) means normal CT does not exclude encephalitis 2, 1
- Be aware that herpetic skin lesions are more confusing than diagnostic, as fever from other causes can precipitate recurrent herpes labialis unrelated to CNS infection 6
Expected Outcomes
Even with optimal early treatment, approximately 30% of patients will either die or have severe neurological deficits 7. Among survivors who regain independence (70%), most have persistent neurological symptoms including: