Dexamethasone in CNS Tuberculosis
Adjunctive dexamethasone should be given to all patients with tuberculous meningitis, tapered over 6-8 weeks, as it provides a significant mortality benefit. 1
Definitive Recommendation
The American Thoracic Society/CDC/IDSA provides a strong recommendation with moderate certainty in evidence for adjunctive corticosteroid therapy with dexamethasone or prednisolone in all patients with tuberculous meningitis, based on systematic review demonstrating mortality benefit. 1, 2
Dosing Regimen
Adults and Children ≥25 kg
- 12 mg/day for 3 weeks, then taper gradually over the following 3 weeks 1, 3, 4
- Alternative approach: taper over 6-8 weeks total duration 1, 2
Children <25 kg
Critical Timing
Initiate dexamethasone before or concurrently with the first dose of anti-tuberculosis medication to maximize benefit by attenuating the inflammatory cascade before it fully develops. 3 Do not delay corticosteroid therapy while awaiting microbiological confirmation—TBM is a medical emergency. 5
Evidence Supporting Use
Mortality Benefit by Disease Severity
The greatest mortality benefit occurs in Stage II disease (lethargic patients): mortality decreased from 40% in controls to 15% with dexamethasone (p=0.02). 1, 3, 4 Six of eight controlled trials demonstrated benefit in terms of survival, frequency of sequelae, or both. 1, 3
For Stage III disease (coma), the mortality benefit was less pronounced but sample sizes were small, potentially precluding detection of effect. 1 For Stage I disease (alert), too few patients were studied to determine effectiveness. 1
Despite this stratified data, all patients with TBM should receive dexamethasone regardless of disease severity, as the overall systematic review demonstrates mortality benefit. 1, 4
Concurrent Anti-Tuberculosis Therapy
Dexamethasone must be given alongside appropriate anti-tuberculosis chemotherapy:
- Initial 2-month intensive phase: Isoniazid, rifampicin, pyrazinamide, and ethambutol (preferred fourth drug for adults) 1, 2
- Continuation phase: Isoniazid and rifampicin for 7-10 additional months 1, 2, 3
- Total treatment duration: 9-12 months (not the 6 months used for pulmonary TB) 2, 5
Monitoring Requirements
- Repeated lumbar punctures to monitor CSF cell count, glucose, and protein, especially early in therapy 1, 3, 4
- Regular neurological assessment for improvement or deterioration 2
- Hepatotoxicity monitoring given the hepatotoxic potential of isoniazid, rifampicin, and pyrazinamide 2
Special Considerations
CNS Tuberculomas Without Meningitis
For isolated CNS tuberculomas (without meningitis), the evidence is less clear. 6 One case series suggests that tuberculomas may require prolonged corticosteroid therapy extending several months to 18 months, as attempts to taper according to standard TBM recommendations led to clinical deterioration with seizures or new lesions. 6 However, this is based on limited case series data and requires verification in controlled studies. 6
The British Infection Society recommends the same treatment approach (including corticosteroids) for both TBM and tuberculomas. 5
Mechanism of Action
Importantly, dexamethasone's clinical benefit in TBM does not appear to work through measurable attenuation of peripheral or local immune responses—the mechanism remains incompletely understood. 7 This challenges previous theories but does not diminish the proven mortality benefit. 7
Critical Pitfalls to Avoid
- Do not withhold dexamethasone while awaiting diagnostic confirmation—start empirically when TBM is suspected 5
- Do not use the 6-month pulmonary TB regimen—CNS TB requires 9-12 months of treatment 2, 5
- Do not taper corticosteroids too rapidly—complete the full 6-8 week taper 1
- Do not use dexamethasone alone—it must be combined with appropriate anti-tuberculosis chemotherapy 1, 5
Neurosurgical Referral Indications
Immediate neurosurgical consultation is warranted for: