What is the diagnosis and management for a patient with a CSF profile showing pleocytosis, normal glucose, and slightly elevated protein?

CSF Analysis: Mild Pleocytosis with Normal Glucose and Mildly Elevated Protein

This CSF profile (27 cells/µL, glucose 60 mg/dL, protein 77 mg/dL) is most consistent with viral meningitis or early viral encephalitis, and you should immediately send CSF PCR for HSV-1, HSV-2, VZV, and enteroviruses while starting empiric acyclovir if any neurological symptoms are present. 1, 2

Immediate Interpretation

• Bacterial meningitis is highly unlikely because CSF protein in bacterial meningitis typically exceeds 220 mg/dL, and a level below 60 mg/dL makes bacterial disease very unlikely—your value of 77 mg/dL falls in the intermediate zone but closer to the viral pattern 1

• The mild pleocytosis (27 cells/µL) with normal glucose and mildly elevated protein is the classic triad of viral meningitis, where protein is mildly elevated with normal or slightly low glucose 1, 3

• Critical missing information: You must obtain a simultaneous plasma glucose to calculate the CSF:plasma glucose ratio (normal >0.66), as the absolute CSF glucose value alone is insufficient for diagnosis 1, 4

• The CSF white cell differential is absolutely essential—lymphocytic predominance confirms viral etiology, while neutrophil predominance (80-95%) would suggest bacterial meningitis 1, 4

Immediate Diagnostic Workup

Send these CSF studies immediately:

• CSF PCR for HSV-1, HSV-2, VZV, and enteroviruses—these account for 90% of viral CNS infections and must be identified rapidly 5, 2

• CSF bacterial culture and Gram stain—to exclude partially treated bacterial meningitis, which can present with lymphocytic pleocytosis and minimal symptoms 2, 6

• CSF lactate level—values <2 mmol/L effectively rule out bacterial disease 1, 2

• CSF cell count with differential—to confirm lymphocytic vs. neutrophilic predominance 1

• Simultaneous plasma glucose—to calculate CSF:plasma glucose ratio 1, 4

Risk-Stratified Additional Testing

If immunocompromised, endemic TB exposure, or subacute presentation (>5 days):

• Send CSF for tuberculosis studies (AFB smear, culture, TB PCR on 6 mL CSF)—TB meningitis classically shows CSF:plasma glucose ratio <0.5, markedly elevated protein (typically >100 mg/dL), and lymphocytic pleocytosis 4, 2

• However, your protein of 77 mg/dL makes TB meningitis less likely, as TB typically shows protein >100 mg/dL 4

If immunocompromised:

• Send CSF cryptococcal antigen and fungal culture—fungal meningitis typically presents with low CSF glucose, which is not present here 1, 2

If considering autoimmune etiology:

• Send CSF oligoclonal bands and IgG index to evaluate for ADEM or multiple sclerosis 1, 2

Empiric Treatment Decision

Start acyclovir 10 mg/kg IV every 8 hours (or 500 mg/m² IV every 8 hours) immediately if ANY of the following are present: 2, 3

• Altered mental status
• Focal neurological deficits
• Seizures
• Inability to closely monitor for clinical deterioration while awaiting PCR results (typically 24-48 hours)

Rationale: 5-10% of HSV encephalitis cases have normal or minimally abnormal initial CSF, and early acyclovir initiation provides potential clinical benefit even if VZV or HSV is ultimately not confirmed 2, 3

Critical Differential Diagnoses to Exclude

Partially treated bacterial meningitis:

• Can present with lymphocytic pleocytosis and minimal symptoms after antibiotic exposure 2
• CSF bacterial culture and Gram stain are essential to exclude this 2

Tuberculous meningitis:

• Your protein of 77 mg/dL is lower than typical TB meningitis (usually >100 mg/dL), making this less likely 4
• If CSF:plasma glucose ratio is <0.5, start empiric four-drug anti-tuberculous therapy immediately without waiting for microbiological confirmation 4

Post-ictal pleocytosis:

• Seizures alone can cause transient CSF pleocytosis (up to 80 cells/µL) with mildly elevated protein 7
• Maximal leukocyte count typically occurs the day after cessation of convulsions 7
• If recent seizure activity, consider this benign cause but still exclude infectious etiologies first 7

Status epilepticus:

• Non-infectious status epilepticus rarely causes CSF pleocytosis (only 6% of cases), but commonly causes elevated protein (44%) and blood-brain barrier dysfunction (55%) 8
• Detection of CSF pleocytosis should prompt further diagnostics for infectious or neoplastic etiology 8

Neuroimaging Requirements

• Obtain brain MRI with and without contrast to identify: 2
  • Temporal lobe enhancement (suggests HSV encephalitis)
  • Basilar meningeal enhancement (suggests TB or fungal meningitis)
  • Demyelinating lesions (suggests autoimmune disease)
  • Leptomeningeal enhancement (suggests malignancy)

Follow-Up Strategy

• Repeat lumbar puncture in 24-48 hours if initial CSF is non-diagnostic and clinical suspicion remains high—HSV PCR can be negative early in disease course 2

• Monitor with serial neurological examinations every 4-6 hours until diagnosis is established 2

• If all infectious workup is negative and patient improves clinically, consider post-ictal pleocytosis or non-infectious causes 8, 7

Common Pitfalls to Avoid

• Do not assume normal CSF excludes bacterial meningitis—early or developing bacterial meningitis can present with minimal or no initial CSF abnormality 6

• Do not rely on absolute CSF glucose alone—always calculate CSF:plasma glucose ratio, as serum glucose abnormalities can mislead interpretation 1, 4

• Do not delay acyclovir if neurological symptoms are present—waiting for PCR results can worsen outcomes in HSV encephalitis 2, 3

• Do not attribute pleocytosis to seizures without excluding infectious causes first—infectious etiologies must be rigorously searched for before diagnosing post-ictal pleocytosis 7