title: 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. guy.thwaites@btinternet.com
authors.forename: Guy E
authors.initials: GE
authors.lastname: Thwaites
authors.forename: Jeremy
authors.initials: J
authors.lastname: Macmullen-Price
authors.forename: Thi Hong Chau
authors.initials: TH
authors.lastname: Tran
authors.forename: Phuong Mai
authors.initials: PM
authors.lastname: Pham
authors.forename: Thi Dung
authors.initials: TD
authors.lastname: Nguyen
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Tinh Hien
authors.initials: TH
authors.lastname: Tran
authors.forename: David
authors.initials: D
authors.lastname: Summers
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Farrar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000209:etiology; D015331:Cohort Studies; D003907:Dexamethasone / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006849:Hydrocephalus / Q000188:drug therapy / Q000209:etiology; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000134:cerebrospinal fluid; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014375:Tuberculoma / Q000188:drug therapy / Q000209:etiology; D014390:Tuberculosis, Meningeal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*
chemical_list: D000893:Anti-Inflammatory Agents; D000995:Antitubercular Agents; D018836:Inflammation Mediators; D003907:Dexamethasone