Corticosteroids for managing tuberculous meningitis

BACKGROUND Tuberculous meningitis, a serious form of tuberculosis that affects the meninges covering the brain and spinal cord, is associated with high mortality and disability among survivors. Corticosteroids have been used as an adjunct to antituberculous drugs to improve the outcome, but their role is controversial. OBJECTIVES To evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis. SEARCH STRATEGY In September 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE, EMBASE, LILACS, and Current Controlled Trials. We also contacted researchers and organizations working in the field, and checked reference lists. SELECTION CRITERIA Randomized controlled trials comparing a corticosteroid plus antituberculous treatment with antituberculous treatment alone in people with clinically diagnosed tuberculosis meningitis and which include death and/or disability as outcome measures. DATA COLLECTION AND ANALYSIS We independently assessed search results and methodological quality, and independently extracted data. We analysed the data using relative risks (RR) with 95% confidence intervals (CI) and the fixed-effect model. We also conducted complete-case and best-worst case analyses. MAIN RESULTS Seven trials involving 1140 participants (with 411 deaths) met the inclusion criteria. All used dexamethasone or prednisolone. Overall, corticosteroids reduced the risk of death (RR 0.78, 95% CI 0.67 to 0.91; 1140 participants, 7 trials). Data on disabling residual neurological deficit from three trials showed that corticosteroids reduce the risk of death or disabling residual neurological deficit (RR 0.82, 95% CI 0.70 to 0.97; 720 participants, 3 trials). Adverse events included gastrointestinal bleeding, bacterial and fungal infections and hyperglycaemia, but they were mild and treatable. AUTHORS' CONCLUSIONS Corticosteroids should be routinely used in HIV-negative people with tuberculous meningitis to reduce death and disabling residual neurological deficit amongst survivors. However, there is not enough evidence to support or refute a similar conclusion for those who are HIV positive.