Dexamethasone in TB Meningitis
Adjunctive dexamethasone is strongly recommended for all patients with tuberculous meningitis, particularly those with decreased level of consciousness, as it reduces mortality and neurological sequelae. 1
Dosing Regimen
Adults and Children ≥25 kg
- 12 mg/day for 3 weeks, then taper over the following 3 weeks 1
- Alternative dosing: 0.4 mg/kg/day (maximum 12 mg/day) intravenously 2
Children <25 kg
- 8 mg/day for 3 weeks, then taper over the following 3 weeks 1
Critical Timing
- Initiate dexamethasone before or concurrently with the first dose of anti-tuberculosis medication 2
- This timing is essential to maximize benefit by attenuating the inflammatory cascade before it fully develops 2
Evidence Supporting Use
Mortality Benefit
- Six of eight controlled trials demonstrated benefit in terms of survival, frequency of sequelae, or both 1
- The greatest mortality benefit was observed in patients with Stage II disease (lethargic presentation): 15% mortality with dexamethasone versus 40% in controls (p<0.02) 1
- For Stage III disease (coma), mortality was 64% with dexamethasone versus 76% in controls, though this did not reach statistical significance due to small sample size 1
Long-Term Outcomes
- Two-year survival probabilities tended to be higher with dexamethasone (0.63 versus 0.55; p=0.07), though five-year survival rates were similar 3
- The benefit may be most pronounced in patients with grade 1 TBM (five-year survival 0.69 versus 0.55, p=0.07) 3
- Disability rates among survivors at five years were similar between groups (13.2% versus 14.7%) 3
Mechanism of Benefit
Pathophysiological Effects
- Reduces hydrocephalus: Fewer patients had hydrocephalus after 60 days with dexamethasone compared to placebo 4
- Prevents infarction: The proportion with basal ganglia infarction after 60 days was halved in the dexamethasone group (27% versus 58%, p=0.130) 4
- Decreases CSF MMP-9 concentrations: Dexamethasone significantly reduced CSF matrix metalloproteinase-9 early in treatment, which correlates with CSF neutrophil count and may represent a key mechanism of benefit 5
Important Clinical Caveats
Paradoxical Reactions
- Tuberculomas may develop during therapy in up to 74% of patients, appearing as a paradoxical reaction 4
- This does not indicate treatment failure and occurs equally in both dexamethasone and placebo groups 1, 4
- Tuberculomas are associated with prolonged fever but not with relapse or poor clinical outcome 4
Monitoring Requirements
- Repeated lumbar punctures should be considered to monitor CSF cell count, glucose, and protein, especially early in therapy 1
- Monitor for steroid-related complications including hyperglycemia, gastrointestinal bleeding, and secondary infections 6
Contraindications and Warnings
- The FDA label warns that corticosteroids may mask signs of infection and decrease resistance to new infections 6
- Salt restriction and potassium supplementation may be necessary due to mineralocorticoid effects 6
- Patients should be carefully monitored if they have latent tuberculosis, as reactivation may occur 6
Treatment Duration
Antituberculosis Chemotherapy
- Initial 2-month phase: INH, RIF, PZA, and EMB 1
- Continuation phase: INH and RIF for an additional 7-10 months after discontinuing PZA and EMB 1
- Total treatment duration is 9-12 months, though optimal duration is not definitively established 1
Route Considerations
- Parenteral forms (INH, RIF, aminoglycosides, fluoroquinolones) are available for patients with altered mental status who cannot take oral medications 1
- A recent trial suggested that oral dexamethasone may be as effective as injectable steroids after the first week, though this cannot be applied to Stage IV TBM or patients with complications like vasculitic infarcts 7