Dexamethasone and Long-Term Outcome of Tuberculous Meningitis in Vietnamese Adults and Adolescents

Abstract

BackgroundDexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown.MethodsVietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability.Results545 patients were randomised to receive either dexamethasone (274 patients) or placebo (271 patients). 50 patients (9.2%) were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07) but five-year survival rates were similar (0.54 versus 0.51, p = 0.51) in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07) but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36). The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7%) and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32).ConclusionsAdjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM.Trial RegistrationClinicalTrials.gov NCT01317654 NCT01317654?term = tuberculous+meningitis&rank = 3

Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis

“…The disability outcome was assessed with the use of the "simple questions" score (based on the answers to two yes-or-no questions regarding the patient's dependency on others in daily activities and whether the illness has left the patient with any other problems) and the modified Rankin score (a disability score that ranges from 0 [no symptoms] to 5 [totally dependent on others]) and was classified as "good outcome," "intermediate outcome," "severe disability," or "death," as described previously. 16,17,19 Patients were assessed at 2, 6, and 9 months after randomization; the worst score from either questionnaire was taken as the outcome. If the 9-month disability assessment was missing, the previous assessment was used instead.…”

Tuberculous Meningitis in Children and Adults: New Insights for an Ancient Foe

“…In the subset of HIV-infected adults enrolled in this trial, there was no benefit of adjunctive corticosteroids on survival or rates of neurologic disability. In a follow-up evaluation of participants in this trial, the survival benefit of dexamethasone continued over a 2-year period from the time of enrollment but was again concentrated among patients with early stage disease [71]. …”

“…Among participants in the clinical trial of dexamethasone in Vietnam, 14% demonstrated severe disability at 5 years of follow-up, with no difference between the dexamethasone and placebo arms [71]. Among HIV-uninfected tuberculous meningitis patients in New York City who successfully completed treatment, there was no additional mortality burden when compared to population age- and sex-matched controls over a 10-year follow-up period, although differences in neurologic morbidities that did not impact survival were not measured [113•].…”

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“…After initial skepticism, steroids are now recommended in TBM [41], based on several clinical trials showing reductions in death and disability [42,43]. There is no evidence of benefit in using steroids in viral encephalitis.…”