Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. Study of TBM pathogenesis is hampered by a lack of experimental models that recapitulate all the features of the human disease. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. Antibiotic regimens for TBM are based on those used to treat pulmonary tuberculosis, which probably results in suboptimal drug levels in the cerebrospinal fluid, owing to poor blood–brain barrier penetrance. The role of adjunctive anti-inflammatory, host-directed therapies — including corticosteroids, aspirin and thalidomide — has not been extensively explored. To address this deficit, two expert meetings were held in 2009 and 2015 to share findings and define research priorities. This Review summarizes historical and current research into TBM and identifies important gaps in our knowledge. We will discuss advances in the understanding of inflammation in TBM and its potential modulation; vascular and hypoxia-mediated tissue injury; the role of intensified antibiotic treatment; and the importance of rapid and accurate diagnostics and supportive care in TBM.

结核病仍然是一个全球性健康问题，2015 年估计有 1,040 万病例和 180 万人因此病死亡。最致命和致残的结核病是结核性脑膜炎 (TBM)，估计新增病例超过 10 万例每年。在合并感染 HIV-1 的患者中，TBM 的死亡率接近 50%。由于缺乏概括人类疾病所有特征的实验模型，TBM 发病机制的研究受到阻碍。 TBM 的诊断常常因疾病确认所需的不敏感且冗长的培养技术而被延误。 TBM 的抗生素治疗方案基于治疗肺结核的治疗方案，由于血脑屏障渗透性差，这可能会导致脑脊液中的药物水平不理想。辅助抗炎、针对宿主的治疗——包括皮质类固醇、阿司匹林和沙利度胺——的作用尚未得到广泛探索。为了解决这一缺陷，2009 年和 2015 年召开了两次专家会议，分享研究结果并确定研究重点。本综述总结了 TBM 的历史和当前研究，并指出了我们知识中的重要差距。我们将讨论对 TBM 炎症及其潜在调节的理解进展；血管和缺氧介导的组织损伤；强化抗生素治疗的作用；以及 TBM 中快速、准确的诊断和支持护理的重要性。