What is the most likely causative pathogen in an elderly patient presenting with confusion, somnolence, and intermittent holocranial headache, with cerebrospinal fluid (CSF) analysis showing lymphocytic predominance, elevated protein, and low glucose?

Mycobacterium tuberculosis is the Most Likely Causative Pathogen

In this elderly patient presenting with subacute confusion, somnolence, and headache with CSF showing lymphocytic predominance (89%), markedly elevated protein (197 mg/dL), low glucose (31 mg/dL with CSF:plasma ratio of 0.30), and elevated opening pressure (300 mm H₂O), Mycobacterium tuberculosis is the most likely diagnosis (Answer A). 1, 2, 3

Key Diagnostic Features Supporting Tuberculous Meningitis

The CSF profile is classic for tuberculous meningitis:

• Low CSF:plasma glucose ratio (<0.5) with lymphocytic pleocytosis strongly suggests tuberculosis, fungal infection, or partially treated bacterial meningitis 1
• Markedly elevated protein (197 mg/dL) is characteristic of tuberculous meningitis, typically ranging 100-200 mg/dL or higher 1
• Subacute presentation over 2 weeks with confusion and somnolence fits the typical indolent course of TB meningitis, unlike the acute presentation of bacterial meningitis 1, 2
• Elevated opening pressure (300 mm H₂O) is common in tuberculous meningitis due to basilar meningeal inflammation 2

Why Other Options Are Less Likely

Neisseria meningitidis (Option B) is excluded because:

• Bacterial meningitis presents acutely (hours to 1-2 days), not over 2 weeks 1
• Neutrophilic predominance (not 89% lymphocytes) would be expected 1, 3
• The patient would be critically ill with high fever and rapid deterioration 1

Schistosoma haematobium (Option C) is unlikely because:

• This parasite primarily causes genitourinary disease, not CNS infection 4
• CNS schistosomiasis would show eosinophilic pleocytosis, not lymphocytic 4
• No mention of endemic exposure or travel history

Human alphaherpesvirus 3/VZV (Option D) is less likely because:

• VZV encephalitis typically shows normal CSF glucose, not the markedly low glucose (31 mg/dL) seen here 5, 6, 7
• VZV CNS infection usually presents more acutely and often follows dermatomal herpes zoster rash 5, 6
• CSF protein elevation in VZV is typically mild to moderate, not 197 mg/dL 5, 8
• The subacute 2-week course with progressive confusion is atypical for VZV 6, 8

Critical Management Considerations

Immediate empiric treatment is essential:

• Start anti-tuberculous therapy immediately without waiting for confirmatory tests, as delays worsen outcomes 2, 3
• Add empiric antibiotics (ceftriaxone + vancomycin + ampicillin) until bacterial meningitis is definitively excluded, as Listeria can present identically with lymphocytic pleocytosis and low glucose in elderly patients 1, 3
• Ampicillin is critical because Listeria accounts for 20-40% of bacterial meningitis in elderly patients and is resistant to cephalosporins 1, 3

Diagnostic workup:

• CSF AFB smear and culture (though sensitivity is only 10-20%) 4
• CSF PCR for M. tuberculosis (higher sensitivity than culture) 4
• Brain MRI with contrast to identify basilar meningeal enhancement characteristic of TB meningitis 3
• HIV testing, as HIV increases risk of tuberculous meningitis 2

Common Pitfalls to Avoid

• Never assume lymphocytic CSF with low glucose is "just viral" - TB meningitis, partially treated bacterial meningitis, and Listeria all present with this pattern 1, 3
• Do not delay treatment waiting for culture confirmation - TB cultures take 2-8 weeks, and untreated TB meningitis has high mortality 2
• Remember that severely immunocompromised patients may have acellular or minimally cellular CSF despite active TB meningitis 2