Table 1. Challenges in tuberculous meningitis.

	Challenges	Implication
Pathogenesis	Mechanism of dissemination from lungs to CSF unclear Mechanisms of CSF invasion unclear	Possible preventative steps/interventions are unclear
Natural History	Why some individuals develop TBM unclear	Focussed prevention therapy not possible
Epidemiology	No good estimates of global TBM incidence No good estimates of overall mortality/ morbidity Unclear differentiation between adult and childhood TBM	Inadequate research funding, inadequate local, country and international health system investment in treatment and diagnosis of TB meningitis Management tailored for children/adults
Diagnosis	Inadequate ability to rule-out TBM Incomplete market penetration of the most effective tests Relatively expensive tests	Many missed cases of TBM Late diagnosis and potentially preventable long-term neurologic disability or mortality Testing unavailable in some settings due to cost
Treatment	Pulmonary TB treatment regimens adapted (with minimal change) to TBM Incomplete understanding of the best treatment for host immune inflammation	Likely inadequate TBM treatment regimens Uncertainty regarding dosing, optimal anti-tuberculous medications Uncertain efficacy/harm of corticosteroids in some populations
Health Systems	Poor community awareness Inadequate diagnostic device access	Missed diagnoses Inadequate resources committed to TBM Missed diagnoses and poor outcomes

CSF, cerebrospinal fluid; TBM, tuberculous meningitis; TB, tuberculosis.