What are the diagnostic criteria and treatment options for tubercular (tuberculosis) meningitis?

Diagnostic Criteria and Treatment of Tuberculous Meningitis

Tuberculous meningitis should be diagnosed using a combination of clinical features, CSF analysis, and microbiological testing, followed by prompt treatment with a four-drug regimen plus adjunctive corticosteroids to reduce mortality. 1

Diagnostic Criteria

Clinical Presentation

• Subacute onset with nonspecific symptoms such as fever, headache, vomiting, and altered mental status developing over days to weeks 2
• Cranial nerve palsies, focal neurological deficits, and signs of increased intracranial pressure may develop as the disease progresses 2
• History of TB exposure or evidence of TB in other sites (particularly lungs) should raise suspicion 1, 2

Cerebrospinal Fluid Analysis

• CSF should be collected prior to initiating antimicrobial therapy whenever possible 1
• Typical CSF findings include:
  • Clear, colorless appearance 2
  • Lymphocytic pleocytosis (predominantly lymphocytes) 1, 2
  • Elevated protein levels 1
  • Low glucose levels (CSF to serum glucose ratio <0.5) 2, 3
• Cell counts and chemistries should be performed on CSF specimens from suspected tuberculous meningitis cases (conditional recommendation, very low-quality evidence) 1

Microbiological Testing

• Multiple CSF samples (large volume, ≥5 mL) should be collected to increase diagnostic yield 1
• Diagnostic tests should include:
  • Acid-fast bacilli (AFB) smear microscopy (sensitivity 40-60% in patients who received prior treatment) 1
  • Mycobacterial culture (gold standard, but sensitivity only 25-70%) 1, 2
  • Nucleic acid amplification tests (NAATs) such as Xpert Ultra (improved sensitivity over conventional methods) 4
  • Adenosine deaminase (ADA) testing in CSF (sensitivity 79%, specificity 91%) 1

Adjunctive Diagnostic Methods

• Blood cultures should be obtained if bacterial meningitis is suspected 1
• Neuroimaging (CT/MRI) may show basal meningeal enhancement, hydrocephalus, tuberculomas, or infarcts 2
• Testing for TB from extraneural sources (sputum, lymph nodes) may support diagnosis 2
• Tuberculin skin test or interferon-gamma release assay may provide supportive evidence 2

Diagnostic Algorithm

When tuberculous meningitis is suspected:

1. Obtain CSF for cell count, chemistry, AFB smear, culture, and molecular testing 1
2. Collect blood cultures and specimens from potential extraneural TB sites 1
3. Perform neuroimaging to identify complications and rule out other causes 2
4. If lumbar puncture is contraindicated (e.g., signs of increased intracranial pressure), start empiric therapy immediately after obtaining blood cultures 5

Treatment Recommendations

Antimicrobial Therapy

• Initial phase (2 months): Isoniazid, rifampin, pyrazinamide, and ethambutol 1
• Continuation phase (7-10 months): Isoniazid and rifampin 1
• Total treatment duration: 9-12 months (longer than pulmonary TB due to severity) 1
• For children, the American Academy of Pediatrics recommends an initial 4-drug regimen of isoniazid, rifampin, pyrazinamide, and either an aminoglycoside or ethionamide, followed by 7-10 months of isoniazid and rifampin 1

Adjunctive Corticosteroid Therapy

• Strong recommendation: Initial adjunctive corticosteroid therapy with dexamethasone or prednisolone tapered over 6-8 weeks for patients with tuberculous meningitis (strong recommendation; moderate certainty in the evidence) 1
• Prednisolone is FDA-approved for tuberculous meningitis with subarachnoid block or impending block (appropriate antituberculous chemotherapy must be used concurrently) 6

Management of Complications

• Monitor for development of hydrocephalus, which may require neurosurgical intervention 7
• Repeated lumbar punctures should be considered to monitor changes in CSF cell count, glucose, and protein, especially early in treatment 1
• Maintain euvolemia and adequate cerebral perfusion pressure in patients with increased intracranial pressure 5

Monitoring and Follow-up

• Clinical improvement should be monitored closely, particularly neurological status 5
• In children, continued growth and development while on treatment usually predicts a positive outcome 1
• If poor treatment response is suspected, consider drug-resistant TB and obtain additional specimens for culture and drug susceptibility testing 1

Important Considerations

• Delay in diagnosis and treatment significantly increases mortality and morbidity 2, 4
• Outcome is closely related to the stage of disease at presentation and patient age 2
• Corticosteroids reduce mortality but may not prevent all neurological sequelae 8
• If TB meningitis is suspected but cannot be confirmed, empiric treatment should be initiated promptly while diagnostic evaluation continues 4