Progress in the Diagnosis and Treatment of Tuberculous Meningitis

Tuberculous meningitis (TBM) is the most severe form of tuberculosis, with high mortality and neurological disability in survivors. Recent advances include improved nucleic-acid diagnostics for cerebrospinal fluid (CSF), refined pediatric regimens, and emerging intensified/adjunctive treatments. Narrative synthesis of current guidelines and peer-reviewed articles (priority on 2019–2025), with an emphasis on pathophysiology, diagnostics, treatment (drug-susceptible and drug-resistant TBM), and age-specific issues. Xpert MTB/RIF or Xpert Ultra should be the first-line CSF tests in adults and children with suspected TBM; the latter has greater sensitivity in paucibacillary syndrome. The use of adjunctive corticosteroids (mortality benefit) remains supported, and trials of high-dose rifampicin and fluoroquinolone add-on have shown mixed clinical outcome improvements, even with improved pharmacokinetics. A 6-month intensive regimen of HRZE-ethionamide has been added as an alternative to the usual 12-month course of treatment for carefully selected, drug-susceptible TBM. With MDR–TB, linezolid and fluoroquinolones have desirable CNS penetration; bedaquiline demonstrates a quantifiable CSF exposure and is being increasingly used as part of MDR–TBM regimens. Early empiric therapy and steroids remain the cornerstone. Quick molecular diagnosis, individualized therapy with CNS-penetrant agents, and adjuncts (e.g., aspirin to decrease infarcts) are transforming care, and large trials are being conducted to clarify the best intensified therapy, particularly in children and in HIV co-infection.