What is the most specific diagnosis for a 21-year-old intravenous drug user presenting with fever, photophobia, neck rigidity, no rash, low cerebrospinal fluid glucose with a CSF‑to‑serum glucose ratio <0.4, and lymphocytic pleocytosis?

Tuberculous Meningitis is the Most Specific Diagnosis

In a 21-year-old IV drug user presenting with fever, photophobia, neck rigidity, no rash, CSF glucose of 2.5 mmol/L (at the lower limit of normal), lymphocytic pleocytosis, and a CSF:serum glucose ratio <0.4, tuberculous (TB) meningitis is the most specific diagnosis. The combination of lymphocytic predominance with a very low CSF:serum glucose ratio is pathognomonic for TB meningitis rather than viral meningitis 1.

Critical Diagnostic Discriminators

CSF:Serum Glucose Ratio is the Key Differentiator

• **A CSF:serum glucose ratio <0.5 is highly suggestive of TB meningitis**, distinguishing it from viral meningitis where the ratio remains >0.36 1, 2, 3.
• A ratio <0.4 in this patient places TB meningitis at the top of the differential, as viral meningitis typically maintains normal or near-normal glucose ratios 1, 4.
• The absolute CSF glucose of 2.5 mmol/L, while technically at the lower limit of normal range, becomes diagnostically significant when the ratio is calculated—a CSF glucose <2.2 mmol/L has 68% sensitivity and 96% specificity for TB meningitis 1, 3.

Lymphocytic Pleocytosis Pattern

• Lymphocytic predominance is characteristic of TB meningitis, though neutrophils may predominate early in the disease course 1, 5.
• Viral meningitis also shows lymphocytic pleocytosis, but the critical difference is the preserved CSF glucose in viral infections (ratio >0.36) 1, 6.
• Bacterial meningitis would typically show neutrophil predominance of 80-95%, not lymphocytic predominance 1, 6.

Why Not Viral Meningitis?

• Viral meningitis maintains a CSF:serum glucose ratio >0.36 and often has completely normal CSF glucose 1, 2, 4.
• The very low glucose ratio (<0.4) effectively excludes viral meningitis as the primary diagnosis 1.
• While viral meningitis can present with fever, photophobia, and neck rigidity with lymphocytic pleocytosis, the low glucose ratio is incompatible with this diagnosis 6, 4.

High-Risk Population Context

• IV drug users have increased risk for TB meningitis due to higher rates of HIV infection, which should be tested immediately 1.
• This patient's risk profile further supports TB meningitis over viral causes 1.

Immediate Management Algorithm

Start Empiric Treatment Immediately

• Initiate four-drug anti-tuberculous therapy (isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin) immediately based on clinical suspicion supported by CSF findings, without waiting for microbiological confirmation 1, 5, 7.
• Simultaneously start IV acyclovir (500 mg/m² every 8 hours) and broad-spectrum antibiotics (ceftriaxone + vancomycin + ampicillin) until bacterial meningitis and HSV encephalitis are definitively excluded 1, 6.

Essential Diagnostic Workup

• Obtain 6 mL of CSF for AFB smear, TB culture, and TB PCR—PCR has 87-100% sensitivity and 98-100% specificity for Mycobacterium tuberculosis 1.
• Measure simultaneous plasma glucose to confirm the CSF:serum ratio calculation 1, 2.
• Send HSV PCR on CSF (>95% sensitivity) to exclude herpes simplex encephalitis 1, 6.
• Perform bacterial cultures and Gram stain to exclude partially treated bacterial meningitis 1, 6.
• Order brain MRI with contrast to evaluate for basal meningeal enhancement, tuberculomas, or infarcts characteristic of TB meningitis 1, 7.
• Test for HIV immediately given the patient's IV drug use history 1.

Common Pitfalls to Avoid

• Do not rely on absolute CSF glucose alone—the CSF:serum ratio is more diagnostically useful than absolute values, especially when serum glucose may be abnormal 1, 2, 3.
• Do not wait for microbiological confirmation before starting anti-TB therapy—delay worsens outcomes, and TB culture can take weeks 1, 5, 7.
• Do not assume viral meningitis based solely on lymphocytic predominance—the glucose ratio is the critical discriminator 1, 6.
• Do not stop empiric antibiotics prematurely—continue until bacterial cultures are negative at 48-72 hours and TB studies are available 1, 6.

Additional Differential Considerations

• Fungal meningitis (Cryptococcus, Histoplasma) can present identically with lymphocytic pleocytosis, low glucose, and elevated protein—obtain cryptococcal antigen, India ink staining, and fungal cultures 1, 6.
• Partially treated bacterial meningitis can shift to lymphocytic predominance after antibiotics, but typically not with such a low glucose ratio 1, 6.
• Listeria monocytogenes can present with lymphocytic predominance in 20-40% of immunocompromised patients, which is why ampicillin must be included in empiric coverage 6.