Should anti-tubercular therapy (ATT) be considered in a patient with cerebral venous thrombosis (CVT) and venous hemorrhagic infarct, and cerebrospinal fluid (CSF) studies showing elevated protein, low sugar, and lymphocytic predominance, but a normal adenosine deaminase (ADA) level, given a concern for tuberculous meningitis?

Should Anti-Tubercular Therapy Be Initiated?

Yes, anti-tubercular therapy (ATT) should be initiated immediately in this patient despite the normal CSF ADA level of 6 U/L, because the clinical presentation of CVT with fever and the CSF profile showing elevated protein (167 mg/dL), low glucose (25 mg/dL), lymphocytic pleocytosis (12 cells with 90% lymphocytes) are highly suggestive of tuberculous meningitis, and the mortality benefit of early treatment far outweighs the risk of delayed diagnosis. 1, 2

Why the Normal ADA Should Not Exclude TB Meningitis

• CSF ADA has significant limitations in sensitivity - while it provides good specificity (91%), the sensitivity is only 79% when using thresholds around 9-10 U/L, meaning approximately 1 in 5 TB meningitis cases will have normal or low ADA levels 2

• The diagnostic accuracy of ADA is threshold-dependent - lower thresholds around 4 U/L provide higher sensitivity (>93%) but your patient's ADA of 6 U/L falls in an intermediate zone where TB cannot be reliably excluded 2

• ADA must be interpreted in the entire clinical context, not as a standalone test - the American Thoracic Society/Infectious Diseases Society of America/CDC guidelines emphasize that ADA provides supportive evidence rather than definitive diagnosis 2

The CSF Profile Strongly Supports TB Meningitis

• Classic TB meningitis CSF findings are present: elevated protein (167 mg/dL), low glucose (25 mg/dL), and lymphocytic predominance (90% lymphocytes) - this triad is characteristic of tuberculous meningitis 1, 3

• The combination of CVT and these CSF findings further supports TB - tuberculous meningitis is a recognized cause of cerebral venous thrombosis, and case reports document this specific presentation 4

Treatment Regimen to Initiate Immediately

Initial Intensive Phase (First 2 Months)

• Four-drug regimen: Isoniazid, rifampin, pyrazinamide, and ethambutol should be started immediately 5, 1, 6, 7, 8

• Dosing for adults 6, 7, 8:

  • Isoniazid: 5 mg/kg up to 300 mg daily
  • Rifampin: Standard dosing per tuberculosis treatment protocols
  • Pyrazinamide: As part of standard four-drug regimen
  • Ethambutol: 15 mg/kg daily (preferred as fourth drug for adults over streptomycin) 5

Continuation Phase (Additional 7-10 Months)

• Two-drug regimen: Continue isoniazid and rifampin for 7-10 additional months after the initial 2-month intensive phase, for a total treatment duration of 9-12 months 5, 1, 9

• This extended duration is critical for CNS tuberculosis - tuberculous meningitis requires longer treatment than pulmonary TB due to poor CNS penetration and high risk of relapse 5, 1

Adjunctive Corticosteroid Therapy is Mandatory

• Dexamethasone should be initiated immediately - adjunctive corticosteroid therapy is strongly recommended for all patients with tuberculous meningitis as it reduces mortality by approximately 30% 5, 1, 9

• Dosing regimen for adults 9:

  • Dexamethasone 12 mg/day (or 0.4 mg/kg/day) for 3 weeks
  • Then taper gradually over the following 3 weeks

• Critical timing: Initiate dexamethasone before or concurrently with the first dose of anti-tuberculosis medication to maximize benefit by attenuating the inflammatory cascade 9

• The mortality benefit is substantial - in Stage II disease, mortality was 15% with dexamethasone versus 40% in controls (p<0.02) 9

Management of the CVT Component

• Anticoagulation should be considered - the case report of CVT secondary to TB meningitis documents successful treatment with low-molecular-weight heparin alongside ATT and steroids 4

• Monitor closely for hemorrhagic transformation - given the venous hemorrhagic infarct already present on MRV, careful neuroimaging follow-up is essential

Monitoring Requirements

• Repeated lumbar punctures should be performed to monitor CSF cell count, glucose, and protein, especially early in therapy 5, 9

• Serial neuroimaging is important given the CVT and hemorrhagic infarct to assess for hydrocephalus, progression of thrombosis, or development of tuberculomas 10

• Drug susceptibility testing should be sent on CSF culture, though treatment should not be delayed while awaiting results 6, 7

Critical Pitfalls to Avoid

• Do not wait for positive AFB smear or culture - CSF AFB smear sensitivity is very low (<5%), and culture sensitivity is only 45-70%, so negative results do not exclude TB meningitis 2, 3

• Do not delay treatment based on normal ADA alone - untreated TB meningitis has devastating morbidity and mortality, and early treatment is crucial for favorable outcomes 1, 2

• Do not use shorter treatment courses - the 6-month regimen adequate for pulmonary TB is insufficient for CNS involvement; 9-12 months is required 5, 1