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

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.

Figures

Figure 1. Common MRI findings in adults with tuberculous meningitis

A: Contrast enhanced axial T1-weighted image reveals thick leptomeningeal enhancement in suprasellar cistern extending into sylvian fissures and ambient cisterns. Temporal horns are also dilated. B: Contrast enhanced axial T1-weighted image reveals leptomeningeal enhancement within cortical sulci and sylvian fissures. Diffuse low signal around sylvian fissures suggests oedematous change. C: Axial T1-weighted image reveals hydrocephalus with dilated lateral and third ventricles. D: Sagittal T1-weighted image following intravenous contrast administration. There is prominent enhancement in the pituitary fossa and along the hypothalamus. The aqueduct of sylvius is clearly patent and third ventricle is dilated. E: Contrast enhanced coronal T1-weighted image. Multiple enhancing nodules, principally parenchymal but also ependymal and leptomeningeal. F: Contrast enhanced coronal T1-weighted image. Marked basal and right sylvian fissure leptomeningeal enhancement is present. Lateral ventricles are dilated. G: Enhanced axial T1-weighted image. There is a large nodular focus of enhancement within the left sylvian fissure extending into the left temporal lobe associated with substantial low-signal change. H: Axial T2-weighted image reveals extensive high signal within left cerebral hemisphere with large heterogeneous signal tuberculoma in sylvian fissure. I: Gadolinium-enhanced T1 coronal imaging showing extensive basal meningeal enhancement and established left capsulostriate lacunar infarct.

Figure 2. Effect of dexamethasone on MRI appearances of tuberculous meningitis during treatment

Proportions of patients with post-contrast enhancement (A), cerebral infarcts (B), tuberculomas (C), and hydrocephalus (D) before and after treatment with dexamethasone (blue bars) or placebo (red bars).