What are the characteristic cerebrospinal fluid findings in tuberculous meningitis and what is the recommended anti‑tuberculosis treatment regimen?

Tuberculous Meningitis: CSF Findings and Treatment

Characteristic CSF Findings

Tuberculous meningitis typically presents with a lymphocytic-predominant pleocytosis, elevated protein (>1 g/L), and low glucose (<2.2 mmol/L) in the cerebrospinal fluid. 1

Key CSF Parameters

• Cell count: 10–500 cells/μL with lymphocytic predominance (>50% lymphocytes) in most cases 2

  • Early in disease, neutrophil predominance (>50%) may occur in 54% of cases and is highly specific (98% specificity) for TBM 2
  • Lymphocytic shift typically develops as disease progresses 1

• Protein: Elevated above 1 g/L in 66% of confirmed cases, with 84% specificity 2

  • Protein levels change slowly over time during treatment 3

• Glucose: Depressed below 2.2 mmol/L in 58% of cases, with very high specificity (98%) 2

  • Glucose normalizes rapidly with treatment in an exponential manner 3

• Adenosine deaminase (ADA): Values >6 U/L strongly support TBM diagnosis with 95% specificity and positive likelihood ratio of 10.7, though sensitivity is only 55% 4

Diagnostic Approach

• At least two of the four independent parameters (protein >1 g/L, glucose <2.2 mmol/L, cell count 10–500/μL, neutrophil predominance >50%) are present in 84% of TBM cases versus only 10% of controls 2

• Acid-fast smear and culture have low sensitivity but yield improves with multiple large-volume CSF samples 1

• PCR has high specificity but suboptimal sensitivity; a negative test does not rule out TBM 1

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Anti-Tuberculosis Treatment Regimen

Initiate immediate four-drug therapy with isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid plus rifampicin for an additional 7–10 months, for a total duration of 9–12 months (preferably 12 months). 56

Intensive Phase (First 2 Months)

• Daily dosing of isoniazid, rifampicin, pyrazinamide, and ethambutol 56

  • Ethambutol is the preferred fourth drug in adults over streptomycin or aminoglycosides 56
  • In children, replace ethambutol with ethionamide or an aminoglycoside because visual-acuity monitoring is unreliable 56

• Daily dosing is strongly preferred over intermittent regimens 56

Continuation Phase (7–10 Additional Months)

• Continue isoniazid plus rifampicin daily after discontinuing pyrazinamide and ethambutol (when isolate is confirmed susceptible) 56

Critical Treatment Duration Error

• A 6-month regimen adequate for pulmonary TB is insufficient for CNS disease and represents the most common critical error in TBM management 56
  • Total treatment must be 9–12 months regardless of CSF normalization 56

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Adjunctive Corticosteroid Therapy

Adjunctive corticosteroids reduce mortality by approximately 25% and must be started immediately before or concurrently with the first anti-TB dose. 567

Adult Dosing

• Dexamethasone 12 mg IV daily (or 0.4 mg/kg/day, maximum 12 mg) for 3 weeks, then taper gradually over the next 3 weeks (total 6-week course) 567

• Alternative: Prednisolone 60 mg oral daily, tapered over 6–8 weeks (e.g., 60 mg × 4 weeks → 30 mg × 4 weeks → 15 mg × 2 weeks → 5 mg × 1 week) 567

  • Oral prednisolone is acceptable when IV access is unavailable 57

Pediatric Dosing

• Children ≥25 kg: Dexamethasone 12 mg IV daily (same as adults) 567
• Children <25 kg: Dexamethasone 8 mg IV daily 567
• Same tapering schedule: 3 weeks full dose, then 3 weeks taper 567

Steroid Benefit by Disease Stage

• Greatest mortality benefit occurs in Stage II (lethargic) disease, reducing mortality from ~40% to ~15% 67

Critical Steroid Safety Points

• Never discontinue steroids abruptly—complete the full 6–8-week taper regardless of clinical improvement to prevent life-threatening adrenal crisis 567

  • Prolonged high-dose corticosteroids suppress the hypothalamic-pituitary-adrenal axis; abrupt cessation causes acute adrenal insufficiency 7

• Development of tuberculomas or paradoxical radiologic worsening does NOT indicate treatment failure and is NOT a reason to stop steroids 67

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Monitoring During Treatment

• Perform repeat lumbar punctures early in therapy to monitor CSF cell count, glucose, and protein 567

  • PMN cells and glucose normalize rapidly (exponential change), allowing early assessment of treatment response 3
  • Lymphocyte count and protein change slowly and have limited clinical utility for monitoring 3

• Monitor liver function tests for hepatotoxicity from isoniazid, rifampicin, and pyrazinamide 56

• Watch for steroid-related complications: hyperglycemia, gastrointestinal bleeding, and secondary bacterial infections 56

• Conduct regular neurological examinations to detect improvement or deterioration 56

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Special Populations

HIV-Positive Patients

• Delay antiretroviral therapy (ART) for 8 weeks after starting anti-TB treatment, even when CD4 <50 cells/μL, to reduce risk of severe or fatal neurological immune reconstitution inflammatory syndrome (IRIS) 56

• For moderate-to-severe paradoxical TB-IRIS, prednisone 1.25 mg/kg/day significantly lowers hospitalization need 56

Drug-Resistant TB

• Manage suspected or confirmed drug-resistant TBM in specialized centers using ≥5 effective drugs, including a fluoroquinolone and an injectable agent 6

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Neurosurgical Referral Indications

Immediate neurosurgical consultation is required for: 56

• Hydrocephalus requiring shunt placement 56
• Tuberculous cerebral abscesses needing drainage 56
• Paraparesis or spinal cord compression from tuberculous lesions 56