Tuberculous Meningitis Across the Lifespan

Abstract

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.

Keywords: adults; children; outcome; pathogenesis; tuberculous meningitis.

Figure 1.

Factors contributing to a vulnerability to tuberculous meningitis across the lifespan. Children have immature immune systems, making them more susceptible to developing active tuberculosis and dissemination of tuberculosis to the brain. The diagnosis of tuberculous meningitis is difficult, often resulting in delayed and severe presentation of the disease. This, together with the inflammatory process in the brain and risk of ischemia, lead to poor neurodevelopmental and neurocognitive outcomes. Adults with tuberculous meningitis are frequently coinfected with human immunodeficiency virus (HIV). The compromised immune system caused by HIV increases the risk of active tuberculosis disease and dissemination. The initiation of antiretroviral therapy to treat HIV puts tuberculous meningitis patients at risk to develop an immune reconstitution inflammatory syndrome (IRIS). Tuberculous meningitis IRIS, together with the ongoing inflammatory process in the brain, and the risk of ischemia leads to unfavorable outcomes. Older people are also at increased risk of late presentation and poor tuberculous meningitis outcomes. Created in BioRender. Rohlwink, U. (2025) https://BioRender.com/b86q069

Figure 2.

Commonly reported characteristics of tuberculous meningitis. Clinical characteristics include fever, vomiting, a decreased level of consciousness, malnourishment, and seizures, headache, meningism, and signs of pulmonary tuberculosis. Imaging findings often show hydrocephalus, basal meningeal enhancement, and infarcts. Cerebrospinal fluid characteristics include elevated white blood cell count, lymphocyte predominance, and increased protein. Created in BioRender. Rohlwink, U. (2025) https://BioRender.com/a03y524