Tuberculous Meningitis in Children and Adults: New Insights for an Ancient Foe

Abstract

Purpose of review: Tuberculous meningitis is the most devastating manifestation of infection with Mycobacterium tuberculosis and represents a medical emergency. Approximately one half of tuberculous meningitis patients die or suffer severe neurologic disability. The goal of this review will be to review the pathogenic, clinical, and radiologic features of tuberculous meningitis and to highlight recent advancements in translational and clinical science.

Recent findings: Pharmacologic therapy includes combination anti-tuberculosis drug regimens and adjunctive corticosteroids. It is becoming clear that a successful treatment outcome depends on an immune response that is neither too weak nor overly robust, and genetic determinants of this immune response may identify which patients will benefit from adjunctive corticosteroids. Recent clinical trials of intensified anti-tuberculosis treatment regimens conducted in Indonesia and Vietnam, motivated by the pharmacologic challenges of treating M. tuberculosis infections of the central nervous system, have yielded conflicting results regarding the survival benefit of intensified treatment regimens. More consistent findings have been observed regarding the relationship between initial anti-tuberculosis drug resistance and mortality among tuberculous meningitis patients. Prompt initiation of anti-tuberculosis treatment for all suspected cases remains a key aspect of management. Priorities for research include the improvement of diagnostic testing strategies and the optimization of host-directed and anti-tuberculosis therapies.

Keywords: Central nervous system infections; Meningitis; Mycobacterial infections; Tuberculosis; Tuberculous meningitis.

Fig. 1

Effect of high-dose intravenous rifampin on survival of Indonesian tuberculous meningitis patients (Reprinted from Lancet Infectious Diseases, Vol 13(1), Rovina Ruslami, A Rizal Ganiem, Sofiati Dian, Lika Apriani, Tri Hanggono Achmad, Andre J van der Ven, George Borm, Rob E Aarnoutse, Reinout van Crevel, Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial, page nos. 27–35, Copyright (2013), with permission from Elsevier)

Fig. 2

Differential efficacy of adjunctive dexamethasone among tuberculous meningitis patients based on LTA4H promoter genotype (Reprinted from Cell, Vol 148(3), David M. Tobin, Francisco J. Roca, Sungwhan F. Oh, Ross McFarland, Thad W. Vickery, John P. Ray, Dennis C. Ko, Yuxia Zou, Nguyen D. Bang, Tran T.H. Chau, Jay C. Vary, Thomas R. Hawn, Sarah J. Dunstan, Jeremy J. Farrar, Guy E. Thwaites, Mary-Claire King et al., Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections, Pages No. 434–46, Copyright (2012), with permission from Elsevier). a Effect of adjunctive dexamethasone on survival across all genotypes. b Survival of patients not treated with dexamethasone, stratified by LTA4H promoter genotype. c Survival of patients treated with dexamethasone, stratified by LTA4H promoter genotype

Fig. 3

Survival of New York City, USA, tuberculous meningitis patients according to initial drug susceptibility testing (C Vinnard et al., Long-term mortality of patients with tuberculous meningitis in New York City: a cohort study, Clinical Infectious Diseases, 2017, volume 64, issue 4, pages 401 to 407, by permission of Oxford University Press). (Fig. 2, panel C, from [113•])