In a patient presenting with a first‑episode status epilepticus and a fever 10 days ago, whose cerebrospinal fluid shows a total cell count of 17 cells/µL with 90 % lymphocytes, normal glucose (99 mg/dL) and normal protein (41 mg/dL), what is the most likely diagnosis and initial management?

Post-Infectious Viral Meningoencephalitis with Status Epilepticus

This presentation is most consistent with post-infectious viral meningoencephalitis, and you should immediately initiate empiric acyclovir for HSV encephalitis while simultaneously covering for bacterial meningitis with ceftriaxone + vancomycin + ampicillin until definitive testing excludes these diagnoses. 1, 2

Why This is Likely Viral Meningoencephalitis

The CSF profile strongly suggests a viral etiology:

• Lymphocytic predominance (90%) with mild pleocytosis (17 cells/µL) is the hallmark pattern of viral CNS infection 1, 2
• Normal glucose (99 mg/dL) essentially rules out tuberculous meningitis, fungal infection, and untreated bacterial meningitis, all of which typically show CSF:plasma glucose ratio <0.5 2, 3
• Normal-to-mildly elevated protein (41 mg/dL) fits viral infection; bacterial and tuberculous meningitis typically show protein >100 mg/dL 1, 3
• Fever 10 days ago followed by status epilepticus suggests a post-infectious encephalitic process rather than acute bacterial meningitis 1, 4

Critical Management Algorithm

Immediate Actions (Within 1 Hour)

1. Start empiric acyclovir immediately for presumed HSV encephalitis, as 5-10% of HSV encephalitis cases have completely normal initial CSF including negative PCR, and a second LP at 24-48 hours may be needed 1, 5

2. Add broad-spectrum antibiotics (ceftriaxone + vancomycin + ampicillin) until bacterial meningitis is definitively excluded 2, 3

   • Ampicillin is non-negotiable because Listeria monocytogenes can present with identical lymphocytic pleocytosis and accounts for 20-40% of bacterial meningitis in elderly/immunocompromised patients 2, 3
   • Listeria is resistant to cephalosporins 2

3. Continue antiepileptic management for status epilepticus per standard protocols

Diagnostic Workup

Send immediately:

• CSF PCR for HSV-1/2, VZV, and enteroviruses (identifies 90% of viral CNS infections) 1, 2
• CSF bacterial culture and Gram stain 1
• Blood cultures 2
• Serum and CSF glucose (simultaneous) to calculate CSF:plasma ratio 1

Obtain within 24 hours:

• Brain MRI with contrast to evaluate for temporal lobe involvement (HSV), parenchymal lesions, or autoimmune patterns 1, 2
• EEG to detect nonconvulsive seizures and assess for temporal lobe abnormalities suggestive of HSV 2

Consider if diagnosis remains unclear:

• Repeat LP at 24-48 hours if initial HSV PCR negative but clinical suspicion remains high 1, 5
• Autoimmune encephalitis antibody panel (NMDA, LGI1, GFAP) if psychiatric symptoms or movement disorders present 2
• HIV testing, as immunocompromised patients can have atypical presentations 3

Critical Pitfalls to Avoid

Do Not Assume Seizures Caused the CSF Pleocytosis

• Status epilepticus does NOT cause CSF pleocytosis 6
• A prospective study of 200 children with fever-associated status epilepticus confirmed that FSE rarely causes pleocytosis; any CSF abnormality must be attributed to an underlying CNS infection 6

Do Not Exclude Bacterial Meningitis Based on Lymphocytic Predominance Alone

• 32% of bacterial meningitis cases with WBC <1,000/mm³ show lymphocytic predominance 7
• Bacterial meningitis can present with lymphocytic CSF, particularly Listeria, partially treated meningitis, and early disease 2, 7
• 10% of bacterial meningitis patients have fewer than 100 cells/mm³ 2, 5

Do Not Wait for PCR Results to Start Treatment

• Treatment must begin within one hour when bacterial or HSV meningitis/encephalitis is suspected 2
• Delayed treatment leads to poor outcomes and increased mortality 2

When to Narrow or Stop Antibiotics

De-escalate antibiotics after 48-72 hours if:

• CSF bacterial culture remains negative 2
• HSV PCR is positive, confirming viral etiology 1
• Clinical improvement on acyclovir alone 1
• No features suggesting tuberculous or fungal infection (normal glucose, lack of basilar meningeal enhancement on MRI) 3

Continue acyclovir for 14-21 days if HSV encephalitis is confirmed or remains the leading diagnosis despite negative initial PCR 1

Alternative Diagnoses to Consider

If the patient does not improve on acyclovir and bacterial cultures are negative:

• Autoimmune encephalitis (anti-NMDA receptor, LGI1): Consider if prominent psychiatric symptoms, movement disorders, or refractory seizures 2
• Tuberculous meningitis: Unlikely given normal glucose, but consider if subacute course >2 weeks, basilar meningeal enhancement on MRI, or endemic exposure 3
• Post-infectious autoimmune process: Can occur after viral infections and present with seizures and mild CSF pleocytosis 2