Tuberculous meningitis remains the most lethal form of tuberculosis. Despite significant physiological differences adults and children with tuberculous meningitis receive similar treatment and are often grouped together in research. Consequently, differences in tuberculous meningitis characteristics across the lifespan are poorly understood but may be relevant to developing more effective and age-appropriate interventions. In this review we discuss potential age-specific considerations in pathogenesis and pathophysiology, and review literature over the last 5 years to describe clinical characteristics, management, and outcomes across age groups. Children aged <5 years are vulnerable to tuberculosis disease and dissemination due to an immature immune system and the developing brain is highly susceptible to injury associated with neuroinflammation, leading to a greater likelihood of disability that has lifelong impact. Amongst adults, those with human immunodeficiency virus and older people are at greatest risk of death, but more research into the frequency of neurocognitive disability is needed.

Understanding neuroimmune responses during brain infections remains challenging because the site of disease (i.e., the brain) is difficult to access, immune responses within the central nervous system (CNS) are spatially and temporally compartmentalized, and peripheral immune cells have largely served as a proxy for the neuroimmune response. Cerebrospinal fluid (CSF) occupies a unique anatomical and immunological position at the interface between the brain parenchyma, CNS border compartments, and the peripheral immune system, making it an important window through which neuroinflammatory processes can be investigated in living patients. In this review, we examine evidence from CNS infections, with particular emphasis on tuberculous meningitis, demonstrating that CSF contains cellular and transcriptional profiles that differ from those observed in peripheral blood and vary according to the anatomical sampling site. We consider how CNS-resident cells, border-associated immune populations, and recruited leukocytes contribute to the neuroimmune environment of CSF. Importantly, we distinguish evidence derived from cells directly recovered from CSF from soluble biomarkers that may reflect activity in parenchymal or border compartments, and from cellular processes inferred from transcriptomic studies. We also discuss how CSF sampling and analytical approaches influence interpretation and highlight the potential of high-dimensional profiling to resolve compartmentalized neuroimmune responses during CNS infection.