Ischaemia in tuberculous meningitis: update on pathophysiology, clinical predictors and management.

purpose of reviewTuberculous meningitis (TBM) is a severe manifestation of Mycobacterium tuberculosis infection, associated with high mortality and long-term neurological disability. Cerebral ischaemia and infarction are major contributors to poor outcomes, yet the underlying mechanisms remain incompletely understood. This review summarises current understanding of the pathophysiology, predictors, and emerging therapies for TBM-associated ischaemia, highlighting critical research priorities. RECENT

findingsStroke in TBM reflects a complex interplay of neuroinflammation, immunothrombosis, and raised intracranial pressure (ICP). Key emerging mediators include neutrophil extracellular traps, matrix metalloproteinases, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), platelet hyperactivation, and dysregulated tryptophan metabolism. Advanced neuroimaging, particularly vessel wall imaging, may improve infarction risk prediction and patient stratification, potentially supported by machine learning approaches. Large trials of adjunctive antiplatelet therapy show limited or inconsistent benefit, while small studies suggest anti-TNF therapy may be beneficial. SUMMARY: Despite progress in characterizing inflammation, thrombosis, and vascular injury in TBM, significant gaps remain in understanding mechanisms and timing of stroke. Improved mechanistic insight, integrated translational research, and trials of novel host-directed therapies are needed to prevent stroke and improve neurological outcomes. In parallel, efforts should focus on optimising existing strategies, particularly defining effective approaches to management of raised ICP.