Cognitive Impairment in Tuberculous Meningitis

Abstract

Background Cognitive impairment is reported as a common complication in adult tuberculous meningitis (TBM), yet few studies have systematically assessed the frequency and nature of impairment. Moreover, the impact of impairment on functioning and medication adherence is not described. Methods A cognitive test battery (10 measures assessing 7 cognitive domains) was administered to 34 participants with HIV-associated TBM 6 months post-diagnosis. Cognitive performance was compared to a comparator group of 66 people living with HIV (PLWH) without a history of TB. A secondary comparison was made between TBM cases and 26 participants with HIV 6-months post diagnosis of TB outside the central nervous system (CNS). Impact on functioning was evaluated, including through assessment of medication adherence. Results In TBM, 16/34 (47%) of participants had low performance on cognitive testing. Cognition was impaired across all domains. Global cognitive performance was significantly lower in TBM cases compared to PLWH (mean T-score 41 vs 48, p < 0.001). TBM cases also had lower global cognition compared to those with non-CNS TB (mean global T score 41 vs 46, p = 0.016). Functional outcomes did not significantly correlate with cognitive performance in the sub-group of participants where this was assessed (n = 19). Conclusions Low cognitive performance following HIV-associated TBM is common. This effect is independent of, and additional to, effects of HIV and non-CNS TB disease. Further studies are needed to understand longer term outcomes, clarify the association with treatment adherence, a key predictor of outcome in TBM, and develop context-specific tools to identify individuals with cognitive difficulties to improve outcomes in TBM.

Acute ischemic stroke in tuberculous meningitis

“…Fourth, our study was focused on the complications caused by stroke in TBM patients. Previous studies have shown that other TBM complications, such as myelitis ( 22 ), vision impairment ( 23 ), cognitive dysfunction ( 24 ), and seizure ( 25 ), similarly affect patients' quality of life. Long-term follow-up and neurological monitoring may be necessary for TBM patients.…”

Interactions between CNS and immune cells in tuberculous meningitis

“…showed that microRNA-124 modulates the proliferation of Mycobacterium by inhibiting the signal transducer and activator of transcription 3 signaling pathway ( 72 ). Although microglia play an immune supervisor role in the CNS, the long-lasting activation of microglia induces hyper-neuroinflammation, which may induce neurotoxicity and impair the cognitive ability in TB patients ( 73 ). As the main component of myeloid cells, microglia infiltration reflects the brain inflammatory activation status in TBM ( 74 ).…”

Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia

“…A retrospective study showed that 144 of 559 (25.8%) patients admitted with TBM had cerebral infarcts diagnosed with brain imaging, with three-quarters of them being acute or subacute [ 30 ]. In addition, hyponatremia and tuberculous brain abscesses are common macroscopic manifestations of TBM, and cognitive impairment occurs in approximately half of the patients with TBM concurrently infected with HIV, which cannot be ascribed to limited focal structural deficits such as tuberculomas [ 6 ]. These characteristics can exist separately or in combination and may not be detected radiographically until the disease has progressed ( Fig.…”

“…Much of the damage caused by TBM results from host-derived inflammatory responses, frequently due to non-productive neuroinflammation, in which microglia play a major initiating role [ 5 ]. Although microglia serve as immune supervisors in the central nervous system (CNS), their prolonged activation causes hyper neuroinflammation, which has the potential to be neurotoxic and impair the cognition of patients [ 6 ].…”