Abstract
Tuberculous meningitis (TBM) results from dissemination of M. tuberculosis to the cerebrospinal fluid (CSF) and meninges. Ischaemia, hydrocephalus and raised intracranial pressure frequently result, leading to extensive brain injury and neurodisability. The global burden of TBM is unclear and it is likely that many cases are undiagnosed, with many treated cases unreported. Untreated, TBM is uniformly fatal, and even if treated, mortality and morbidity are high. Young age and human immunodeficiency virus (HIV) infection are potent risk factors for TBM, while Bacillus Calmette-Guérin (BCG) vaccination is protective, particularly in young children. Diagnosis of TBM usually relies on characteristic clinical symptoms and signs, together with consistent neuroimaging and CSF parameters. The ability to confirm the TBM diagnosis via CSF isolation of M. tuberculosis depends on the type of diagnostic tests available. In most cases, the diagnosis remains unconfirmed. GeneXpert MTB/RIF and the next generation Xpert Ultra offer improved sensitivity and rapid turnaround times, and while roll-out has scaled up, availability remains limited. Many locations rely only on acid fast bacilli smear, which is insensitive. Treatment regimens for TBM are based on evidence for pulmonary tuberculosis treatment, with little consideration to CSF penetration or mode of drug action required. The World Health Organization recommends a 12-month treatment course, although data on which to base this duration is lacking. New treatment regimens and drug dosages are under evaluation, with much higher dosages of rifampicin and the inclusion of fluoroquinolones and linezolid identified as promising innovations. The inclusion of corticosteroids at the start of treatment has been demonstrated to reduce mortality in HIV-negative individuals but whether they are universally beneficial is unclear. Other host-directed therapies show promise but evidence for widespread use is lacking. Finally, the management of TBM within health systems is sub-optimal, with drop-offs at every stage in the care cascade.
Highlights
Tuberculous meningitis (TBM) is an extra-pulmonary form of tuberculosis (TB) characterised by sub-acute or chronic inflammation of the meninges as a result of invasion of the sub-arachnoid space by the bacilli M. tuberculosis
Other forms of central nervous system (CNS) TB such as tuberculoma, cerebral abscess, and spinal TB are not categorised as TBM, even though treatment is similar
In this review we describe the current global situation for TBM in terms of our understanding of the pathogenesis and natural history, epidemiology, diagnosis, and treatment
Summary
Tuberculous meningitis (TBM) is an extra-pulmonary form of tuberculosis (TB) characterised by sub-acute or chronic inflammation of the meninges as a result of invasion of the sub-arachnoid space by the bacilli M. tuberculosis. Autopsy studies in adults with HIV have found high proportions of TB co-infection, commonly with extrapulmonary disease, including meningitis, which is frequently undiagnosed and untreated prior to death[40] Even those cases diagnosed may not be appropriately reported as individuals with TBM are usually diagnosed in hospitals, which in some contexts, are less likely to be reporting units for TB41. Use of adjunctive aspirin has been shown to be beneficial in adults with TBM103,104, with one recent study of high dose aspirin demonstrating prevention of new cerebral infarction in adults[105] This effect, has not been demonstrated in children and requires larger randomised trials in adults[106]. No linezolid in treatment regimen at Survival within five years n/s any point
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