Steroids in TB Meningitis
Adjunctive corticosteroids (dexamethasone or prednisolone) should be routinely administered to all patients with tuberculous meningitis, tapered over 6-8 weeks, as they reduce mortality by approximately 25%. 1, 2
Strength of Recommendation
The American Thoracic Society, CDC, and Infectious Diseases Society of America provide a strong recommendation for adjunctive corticosteroids in TB meningitis based on moderate certainty evidence. 1 This recommendation is supported by Cochrane meta-analysis showing corticosteroids reduce death (RR 0.75,95% CI 0.65-0.87) when analyzing 1337 participants across nine trials. 3
Dosing Regimens
Adult Dosing - Two Options:
Dexamethasone (preferred for IV administration):
- Initial dose: 0.4 mg/kg/day (maximum 12 mg/day) given intravenously for 3 weeks 1
- Tapering: Gradually decrease over the following 3 weeks (total 6 weeks) 1
Prednisolone (oral alternative):
- Initial dose: 60 mg/day orally 1
- Alternative tapering schedule: 60 mg/day for 4 weeks → 30 mg/day for 4 weeks → 15 mg/day for 2 weeks → 5 mg/day for week 11 1
- Total duration: 6-8 weeks with gradual taper 1, 2
Pediatric Dosing:
- Children <25 kg: Dexamethasone 8 mg/day 1
- Children ≥25 kg: Dexamethasone 12 mg/day (adult dose) 1
- Duration: 3 weeks at initial dose, then taper over 3 weeks 1
Critical Timing
Corticosteroids must be initiated before or concurrently with the first dose of anti-tuberculosis medication for maximum benefit. 1 Delaying steroid initiation reduces the mortality benefit.
Anti-TB Therapy Backbone
Corticosteroids are adjunctive therapy and must be combined with standard anti-TB treatment:
- Initial phase (2 months): Isoniazid, rifampin, pyrazinamide, and ethambutol 1, 2
- Continuation phase (7-10 months): Isoniazid and rifampin 1, 2
- Total duration: 9-12 months (longer than pulmonary TB due to CNS involvement) 1, 2
Why Tapering is Non-Negotiable
The gradual taper over 6-8 weeks serves two critical physiological purposes:
Prevents adrenal crisis: High-dose corticosteroids for 6-8 weeks suppress the hypothalamic-pituitary-adrenal axis, and abrupt discontinuation can cause life-threatening adrenal insufficiency. 1
Maintains anti-inflammatory effect: The taper maintains therapeutic corticosteroid levels during the critical inflammatory period while allowing adrenal glands to resume normal cortisol production. 1
Common Pitfalls to Avoid
Never stop corticosteroids abruptly, even if the patient appears clinically improved—complete the full 6-8 week tapered course regardless of clinical response. 1
Paradoxical tuberculomas may develop during therapy—this represents an immune reconstitution phenomenon and is NOT treatment failure or a reason to discontinue steroids. 1
Complete the full tapered course even in comatose patients (Stage III disease), as the mortality benefit applies across all disease severity stages. 1
Effect on Outcomes
Mortality reduction: Corticosteroids reduce death by approximately 25% (RR 0.75,95% CI 0.65-0.87), with the most pronounced benefit in Stage II disease (lethargic presentation). 1, 3
Disability: The effect on disabling neurological deficit is less clear, with steroids showing no significant reduction (RR 0.92,95% CI 0.71 to 1.20), though this outcome is less common than death. 3 One older trial from 1996 suggested prednisolone was not beneficial in patients with severe brain lesions or increased intracranial pressure, but this contradicts the stronger, more recent guideline evidence. 4
HIV-Positive Patients
The evidence for HIV-positive patients is limited but suggests similar benefit. One trial showed no heterogeneity by HIV status, with point estimates for death (RR 0.90) similar to HIV-negative participants. 3 However, the European Respiratory Society recommends using corticosteroids with caution in HIV-infected patients. 1 Given the limited data, the same dosing regimen should be used but with heightened monitoring for opportunistic infections.
Monitoring During Treatment
- Monitor for adverse events including gastrointestinal bleeding, bacterial/fungal infections, and hyperglycemia—these are generally mild and treatable. 5, 3
- Consider repeated lumbar punctures to monitor CSF parameters, especially early in therapy. 1
- Monitor neurological status closely for treatment response. 2
Long-Term Outcomes
One trial with 5-year follow-up showed the mortality benefit was no longer apparent at this extended time-point (RR 0.93,95% CI 0.78 to 1.12), suggesting the primary benefit is in reducing early mortality during the acute inflammatory phase. 3