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. Summary 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.

Metagenomic next generation sequencing for the diagnosis of tuberculosis meningitis: A systematic review and meta-analysis

“…Similar to other types of EPTB, the paucibacillary nature makes early diagnosis of TBM more difficult [26]. Delays in the diagnosis and treatment of TBM can lead to serious complications PLOS ONE such as severe disability or death.…”

Analysis of Tuberculosis Meningitis Pathogenesis, Diagnosis, and Treatment

“…Extrapulmonary TB begins when the bacteria disseminate from the lungs to the lymph nodes, and during this time, there is bacteremia which seed M. tuberculosis to other organs in the body for TB, specifically the meninges and the brain parenchyma [ 17 , 18 ]. During hematogenous dissemination, mycobacteria may be deposited adjacent to the ventricles or subarachnoid space, leading to granuloma formation at those sites of deposition [ 19 , 20 ]. M. tuberculosis can breach the blood brain barrier (BBB) extracellularly or intracellularly via dendritic cells or macrophages [ 17 , 21 ].…”

“…TBM occurs when subependymal or subpial tubercles, also known as “rich foci” seed during bacillemia of primary infection or disseminated disease [ 17 , 18 , 22 , 23 ]. This rupture of the granuloma into the subarachnoid space leads to an intense inflammatory response, which eventually causes meningitis [ 18 , 19 , 21 , 23 ]. The tissue damage seen in the brain is due to a host inflammatory response rather than over-replication in the CSF [ 21 , 23 ].…”

“…The inflammatory response is due to rupture which includes a collection of a tuberculous, thick gelatinous exudate (erythrocytes, mononuclear cells, neutrophils, and bacilli) at the basal brain and vasculitis within the cerebral arterial system, including branches of the middle cerebral artery, the vertebrobasilar system, and the vessels of the Circle of Willis [ 18 , 19 , 24 ]. All of this can lead to long-term neurological defects from either infarction or compression by the exudate, which can encase cranial nerves and cause nerve palsies, entrapment of blood vessels, and blocking of CSF flow in the cerebral aqueduct to cause hydrocephalus.…”

“…All of this can lead to long-term neurological defects from either infarction or compression by the exudate, which can encase cranial nerves and cause nerve palsies, entrapment of blood vessels, and blocking of CSF flow in the cerebral aqueduct to cause hydrocephalus. These processes produce adhesions, obliterative vasculitis (internal carotid, middle cerebral arteries), and encephalitis [ 18 , 19 , 23 ].…”