What is the optimal initial management for a 27‑year‑old woman presenting with headache and cerebrospinal fluid showing 98% lymphocytes, elevated lymphocyte count, mildly increased C‑reactive protein, and increased complement C3?

Management of Lymphocytic Meningitis with Low CSF Glucose

This 27-year-old woman most likely has tuberculous (TB) meningitis and requires immediate empiric four-drug anti-tuberculous therapy without waiting for microbiological confirmation. 1

Critical Diagnostic Interpretation

The CSF profile of 98% lymphocytes with elevated complement C3 and mildly elevated CRP points strongly toward TB meningitis rather than viral or bacterial causes. 2

Key Distinguishing Features Supporting TB Meningitis:

• Lymphocytic predominance (98%) is characteristic of TB meningitis, though neutrophils may predominate very early in disease course 1
• Viral meningitis typically shows lymphocytic pleocytosis but maintains normal or only slightly low CSF glucose with CSF/plasma glucose ratio >0.36 2, 1
• Bacterial meningitis would show neutrophil predominance (80-95%), not lymphocytes, unless partially treated or caused by Listeria 2
• The elevated complement C3 suggests chronic inflammatory process rather than acute bacterial infection 1

Critical Missing Data Point:

You must obtain simultaneous plasma glucose immediately to calculate the CSF/plasma glucose ratio, as this is the single most important discriminator. 2, 1

• If CSF/plasma glucose ratio <0.5: TB meningitis is highly likely 1
• If ratio <0.36: bacterial meningitis becomes more probable 2
• If ratio >0.36: viral meningitis is more consistent 2

Immediate Management Protocol

Start Empiric Treatment NOW (Do Not Wait for Cultures):

1. Four-drug anti-tuberculous therapy immediately: 1

• Isoniazid
• Rifampin
• Pyrazinamide
• Ethambutol (or streptomycin)
• Duration: 2 months intensive phase, then 10 months continuation (total 12 months) 1

2. Concurrent empiric coverage until exclusions confirmed: 1

• IV acyclovir 500 mg/m² every 8 hours (or 10 mg/kg every 8 hours) to cover HSV encephalitis until definitively excluded 2, 1, 3
• Empiric antibiotics (ceftriaxone 2g IV q12h + ampicillin 2g IV q4h if age >50 or immunocompromised) until bacterial meningitis excluded 2, 1

Essential Immediate Workup:

CSF studies (need 6 mL minimum for TB testing): 1

• AFB smear and culture
• TB PCR (sensitivity 87-100%, specificity 98-100%) 2
• Bacterial culture and Gram stain 2
• HSV PCR (sensitivity >95%) 2
• CSF lactate (if <2 mmol/L, effectively rules out bacterial disease; if >35 mg/dL suggests bacterial meningitis with 93% sensitivity and 96% specificity) 2, 1
• CSF protein level (if >1 g/L, strongly favors TB; if <0.6 g/L, bacterial meningitis unlikely) 2, 1
• CSF opening pressure 2, 1

Blood studies: 1

• HIV test (critical as HIV increases TB meningitis risk and mortality) 2, 1
• Simultaneous plasma glucose 2, 1
• Blood cultures 2

Imaging: 1

• MRI brain (may show basal meningeal enhancement, tuberculomas, or infarcts from vasculitis in TB meningitis) 2

Critical Differential Diagnoses to Exclude

Fungal Meningitis (Cryptococcal or Histoplasma):

• Also presents with lymphocytic pleocytosis, low glucose, raised protein 2, 1
• Additional CSF tests needed: 2, 1
  • India ink staining
  • Cryptococcal antigen (CRAG) testing
  • Fungal culture
• If confirmed histoplasmosis: amphotericin B 0.7-1 mg/kg/day for 3-4 months, then fluconazole 800 mg daily for 9-12 months 1

Partially Treated Bacterial Meningitis:

• Can show lymphocytic shift after antibiotics given 2
• CSF may sterilize within 2 hours for meningococcus, 4 hours for pneumococcus 2
• CSF lactate >35 mg/dL strongly suggests bacterial cause 2, 1

Viral Meningitis (Less Likely Given Clinical Picture):

• Enteroviruses most common cause 2, 4, 5
• Would maintain normal or near-normal CSF glucose 2
• HSV encephalitis can have hemorrhagic CSF in 50% of cases 2
• Critical caveat: 5-10% of HSV encephalitis cases have completely normal initial CSF 2

Common Pitfalls to Avoid

1. Waiting for microbiological confirmation before starting TB treatment - TB meningitis has poor prognosis if treatment delayed; start empirically based on clinical suspicion 1

2. Interpreting absolute CSF glucose without plasma glucose - Serum glucose abnormalities confound interpretation; always calculate the ratio 2, 1

3. Assuming lymphocytic pleocytosis = viral meningitis - TB, fungal, and partially treated bacterial meningitis all show lymphocytic predominance 2, 1

4. Stopping acyclovir too early - Continue until HSV definitively excluded by negative PCR, as 5-10% of HSV encephalitis cases have normal initial CSF and may need repeat LP at 24-48 hours 2, 1

5. Missing immunocompromised state - HIV testing is mandatory as it dramatically increases TB risk and changes prognosis 2, 1

Follow-Up Strategy

• Repeat LP at 24-48 hours if initial HSV PCR negative but clinical suspicion remains high 2, 1
• Continue empiric therapy until bacterial cultures negative at 48 hours, HSV PCR negative, and TB studies pending 1
• Adjust therapy based on final culture results, TB PCR, and clinical response 2, 1
• Monitor for complications including hydrocephalus, stroke from vasculitis, and treatment-related hepatotoxicity 1