title: Tuberculous meningitis: advances in diagnosis and treatment.
abstract: BACKGROUND
  Tuberculous meningitis (TBM) is the most severe form of infection caused by Mycobacterium tuberculosis, causing death or disability in more than half of those affected. The aim of this review is to examine recent advances in our understanding of TBM, focussing on the diagnosis and treatment of this devastating condition.
  
  
  METHODS
  Papers on TBM published between 1891 and 2014 and indexed in the NCBI Pubmed. The following search terms were used: TBM, diagnosis, treatment and outcome.
  
  
  RESULTS
  The diagnosis of TBM remains difficult as its presentation is non-specific and may mimic other causes of chronic meningoencephalitis. Rapid recognition of TBM is crucial, however, as delays in initiating treatment are associated with poor outcome. The laboratory diagnosis of TBM is hampered by the low sensitivity of cerebrospinal fluid microscopy and the slow growth of M. tuberculosis in conventional culture systems. The current therapy of TBM is based on the treatment of pulmonary tuberculosis, which may not be ideal. The combination of TBM and HIV infection poses additional management challenges because of the need to treat both infections and the complications associated with them.
  
  
  RESULTS
  The pathogenesis of TBM remains incompletely understood limiting the development of interventions to improve outcome. The optimal therapy of TBM has not been established in clinical trials, and increasing antimicrobial resistance threatens successful treatment of this condition. The use of adjunctive anti-inflammatory agents remains controversial, and their mechanism of action remains incompletely understood. The role of surgical intervention is uncertain and may not be available in areas where TBM is common.
  
  
  CONCLUSIONS
  Laboratory methods to improve the rapid diagnosis of TBM are urgently required. Clinical trials of examining the use of high-dose rifampicin and/or fluoroquinolones are likely to report in the near future.
  
  
  CONCLUSIONS
  The use of biomarkers to improve the rapid diagnosis of TBM warrants further investigation. The role of novel antituberculosis drugs, such as bedaquiline and PA-824, in the treatment of TBM remains to be explored. Human genetic polymorphisms may explain the heterogeneity of response to anti-inflammatory therapies and could potentially be used to tailor therapy.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Box 157, Hills Road, Cambridge CB2 0QQ, UK Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK Public Health England, Clinical Microbiology and Public Health Laboratory, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK et317@medschl.cam.ac.uk estee.torok@addenbrookes.nhs.uk.
authors.forename: M E
authors.initials: ME
authors.lastname: Török
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000379:methods*; D054884:Host-Pathogen Interactions; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D017410:Practice Guidelines as Topic; D011718:Pyrazinamide / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage; D016896:Treatment Outcome; D014390:Tuberculosis, Meningeal / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin
keywords: diagnosis; meningitis; treatment; tuberculosis; tuberculous meningitis