Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis: an observational study

Guy E. Thwaites, Jeremy Macmullen-Price, Tran Thi Hong Chau, Pham Phuong Mai, Nguyen Thi Dung, Cameron P. Simmons, Nicholas J. White, Tran Tinh Hien, David Summers, Jeremy J. Farrar

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Adjunctive dexamethasone increases survival from tuberculous meningitis, but the underlying mechanism is unclear. We aimed to determine the effect of dexamethasone on cerebral MRI changes and their association with intracerebral inflammatory responses and clinical outcome in adults treated for tuberculous meningitis. Methods: Cerebral MRI was undertaken, when possible, at diagnosis and after 60 days and 270 days of treatment in adults with tuberculous meningitis admitted to two hospitals in Vietnam. Patients were randomly assigned either dexamethasone (n=24) or placebo (n=19) and received 9 months of treatment with standard first-line antituberculosis drugs. We assessed associations between MRI findings, treatment allocation, and resolution of fever, coma, cerebrospinal fluid inflammation, and neurological outcome. Findings: 83 scans were done for 43 patients: 19 given placebo, 24 given dexamethasone. Basal meningeal enhancement (82%) and hydrocephalus (77%) were the most common presenting findings. Fewer patients had hydrocephalus after 60 days of treatment with dexamethasone than after placebo treatment (p=0·217). Tuberculomas developed in 74% of patients during treatment and in equal proportions in the treatment groups; they were associated with long-term fever, but not relapse or poor clinical outcome. The basal ganglia were the most common site of infarction; the proportion with infarction after 60 days was halved in the dexamethasone group (27% vs 58%, p=0·130). Interpretation: Dexamethasone may affect outcome from tuberculous meningitis by reducing hydrocephalus and preventing infarction. The effect may have been under-estimated because the most severe patients could not be scanned.

Original languageEnglish
Pages (from-to)230-236
Number of pages7
JournalLancet Neurology
Volume6
Issue number3
DOIs
Publication statusPublished - 1 Mar 2007

Cite this

Thwaites, Guy E. ; Macmullen-Price, Jeremy ; Chau, Tran Thi Hong ; Phuong Mai, Pham ; Dung, Nguyen Thi ; Simmons, Cameron P. ; White, Nicholas J. ; Hien, Tran Tinh ; Summers, David ; Farrar, Jeremy J. / Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis : an observational study. In: Lancet Neurology. 2007 ; Vol. 6, No. 3. pp. 230-236.
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abstract = "Background: Adjunctive dexamethasone increases survival from tuberculous meningitis, but the underlying mechanism is unclear. We aimed to determine the effect of dexamethasone on cerebral MRI changes and their association with intracerebral inflammatory responses and clinical outcome in adults treated for tuberculous meningitis. Methods: Cerebral MRI was undertaken, when possible, at diagnosis and after 60 days and 270 days of treatment in adults with tuberculous meningitis admitted to two hospitals in Vietnam. Patients were randomly assigned either dexamethasone (n=24) or placebo (n=19) and received 9 months of treatment with standard first-line antituberculosis drugs. We assessed associations between MRI findings, treatment allocation, and resolution of fever, coma, cerebrospinal fluid inflammation, and neurological outcome. Findings: 83 scans were done for 43 patients: 19 given placebo, 24 given dexamethasone. Basal meningeal enhancement (82{\%}) and hydrocephalus (77{\%}) were the most common presenting findings. Fewer patients had hydrocephalus after 60 days of treatment with dexamethasone than after placebo treatment (p=0·217). Tuberculomas developed in 74{\%} of patients during treatment and in equal proportions in the treatment groups; they were associated with long-term fever, but not relapse or poor clinical outcome. The basal ganglia were the most common site of infarction; the proportion with infarction after 60 days was halved in the dexamethasone group (27{\%} vs 58{\%}, p=0·130). Interpretation: Dexamethasone may affect outcome from tuberculous meningitis by reducing hydrocephalus and preventing infarction. The effect may have been under-estimated because the most severe patients could not be scanned.",
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Thwaites, GE, Macmullen-Price, J, Chau, TTH, Phuong Mai, P, Dung, NT, Simmons, CP, White, NJ, Hien, TT, Summers, D & Farrar, JJ 2007, 'Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis: an observational study' Lancet Neurology, vol. 6, no. 3, pp. 230-236. https://doi.org/10.1016/S1474-4422(07)70034-0

Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis : an observational study. / Thwaites, Guy E.; Macmullen-Price, Jeremy; Chau, Tran Thi Hong; Phuong Mai, Pham; Dung, Nguyen Thi; Simmons, Cameron P.; White, Nicholas J.; Hien, Tran Tinh; Summers, David; Farrar, Jeremy J.

In: Lancet Neurology, Vol. 6, No. 3, 01.03.2007, p. 230-236.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis

T2 - an observational study

AU - Thwaites, Guy E.

AU - Macmullen-Price, Jeremy

AU - Chau, Tran Thi Hong

AU - Phuong Mai, Pham

AU - Dung, Nguyen Thi

AU - Simmons, Cameron P.

AU - White, Nicholas J.

AU - Hien, Tran Tinh

AU - Summers, David

AU - Farrar, Jeremy J.

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N2 - Background: Adjunctive dexamethasone increases survival from tuberculous meningitis, but the underlying mechanism is unclear. We aimed to determine the effect of dexamethasone on cerebral MRI changes and their association with intracerebral inflammatory responses and clinical outcome in adults treated for tuberculous meningitis. Methods: Cerebral MRI was undertaken, when possible, at diagnosis and after 60 days and 270 days of treatment in adults with tuberculous meningitis admitted to two hospitals in Vietnam. Patients were randomly assigned either dexamethasone (n=24) or placebo (n=19) and received 9 months of treatment with standard first-line antituberculosis drugs. We assessed associations between MRI findings, treatment allocation, and resolution of fever, coma, cerebrospinal fluid inflammation, and neurological outcome. Findings: 83 scans were done for 43 patients: 19 given placebo, 24 given dexamethasone. Basal meningeal enhancement (82%) and hydrocephalus (77%) were the most common presenting findings. Fewer patients had hydrocephalus after 60 days of treatment with dexamethasone than after placebo treatment (p=0·217). Tuberculomas developed in 74% of patients during treatment and in equal proportions in the treatment groups; they were associated with long-term fever, but not relapse or poor clinical outcome. The basal ganglia were the most common site of infarction; the proportion with infarction after 60 days was halved in the dexamethasone group (27% vs 58%, p=0·130). Interpretation: Dexamethasone may affect outcome from tuberculous meningitis by reducing hydrocephalus and preventing infarction. The effect may have been under-estimated because the most severe patients could not be scanned.

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