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健康问题，2015 年估计有 1,040 万例病例和 180 万例死亡。结核病最致命和致残的形式是结核性脑膜炎 (TBM)，估计会出现超过 100,000 例新病例每年。在合并感染 HIV-1 的患者中，TBM 的死亡率接近 50%。由于缺乏能够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 的诊断通常会因疾病确认所需的不敏感和冗长的培养技术而延迟。TBM 的抗生素方案基于用于治疗肺结核的方案，由于血脑屏障渗透性差，这可能导致脑脊液中的药物水平不理想。辅助抗炎、宿主导向疗法——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。为了解决这一问题，2009 年和 2015 年召开了两次专家会议，以分享研究结果并确定研究重点。本评论总结了 TBM 的历史和当前研究，并确定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方面的进展；血管和缺氧介导的组织损伤；强化抗生素治疗的作用；以及在 TBM 中快速准确的诊断和支持性护理的重要性。2009 年和 2015 年举行了两次专家会议，以分享研究结果并确定研究重点。本评论总结了 TBM 的历史和当前研究，并确定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方面的进展；血管和缺氧介导的组织损伤；强化抗生素治疗的作用；以及在 TBM 中快速准确的诊断和支持性护理的重要性。2009 年和 2015 年举行了两次专家会议，以分享研究结果并确定研究重点。本评论总结了 TBM 的历史和当前研究，并确定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方面的进展；血管和缺氧介导的组织损伤；强化抗生素治疗的作用；以及在 TBM 中快速准确的诊断和支持性护理的重要性。