What is the role of dexamethasone (corticosteroid) in the treatment of Tuberculous (TB) meningitis?

Role of Dexamethasone in Tuberculous Meningitis

Adjunctive dexamethasone therapy is strongly recommended for all patients with tuberculous meningitis, particularly those with decreased level of consciousness, as it reduces mortality and neurological sequelae. 1

Rationale and Evidence

• Tuberculous meningitis is associated with high mortality and morbidity despite prompt initiation of adequate antituberculous chemotherapy 1
• Dexamethasone reduces mortality from tuberculous meningitis by approximately 25% in the short term (RR 0.75,95% CI 0.65 to 0.87) 2
• Six of eight controlled trials have shown benefit of corticosteroid therapy in terms of survival, frequency of sequelae, or both 1
• The greatest benefit was observed in patients with Stage II disease (lethargic) with mortality of 15% in the dexamethasone group versus 40% in the control group (p<0.02) 1

Mechanism of Action

• Dexamethasone may improve outcomes by:
  • Reducing hydrocephalus development during treatment 3
  • Preventing infarction, particularly in the basal ganglia 3
  • Modulating acute cerebrospinal fluid protein concentrations 4
  • Marginally reducing IFN-gamma concentrations in CSF 4

Dosing Recommendations

• For adults and children weighing ≥25 kg: 12 mg/day initially 1
• For children weighing <25 kg: 8 mg/day initially 1
• Initial dose given for 3 weeks, then decreased gradually over the following 3 weeks 1

Treatment Duration

• The recommended regimen includes an initial 3 weeks at full dose followed by 3 weeks of gradual dose reduction 1
• Long-term follow-up (5 years) shows that the survival benefit may not persist beyond 2 years in all patients 5
• The benefit may be more sustained in patients with grade 1 (mild) tuberculous meningitis 5

Special Considerations

Timing of Administration

• Dexamethasone should be started concurrently with antituberculous therapy 1
• The FDA label notes that dexamethasone use in active tuberculosis should be restricted to cases of fulminating or disseminated tuberculosis where corticosteroids are used for management of the disease in conjunction with appropriate antituberculous regimen 6

Precautions

• Corticosteroids may mask signs of infection and decrease resistance to new infections 6
• If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur 6
• During prolonged corticosteroid therapy, patients should receive chemoprophylaxis 6

Impact on Disability and Long-term Outcomes

• Dexamethasone may have little or no effect on disabling neurological deficits among survivors (RR 0.92,95% CI 0.71 to 1.20) 2
• At five years, there was no significant difference in the proportion of severely disabled patients between dexamethasone and placebo groups (13.2% vs 14.7%) 5
• Tuberculomas may develop during treatment in approximately 74% of patients regardless of dexamethasone use and are associated with long-term fever but not with poor clinical outcomes 3

Conclusion

Dexamethasone is a valuable adjunctive therapy in tuberculous meningitis that reduces mortality, particularly in the first two years after diagnosis. The greatest benefit appears to be in patients with moderate disease severity, though all patients with tuberculous meningitis should receive dexamethasone unless contraindicated.