Long-term Cognitive Outcomes in Tuberculous Meningitis

Abstract

Objective: Data on cognitive changes in patients with tuberculous meningitis (TBM) are sparse. We aimed to study the cognitive profiles of patients with grade I TBM and correlate them with the cytokine values.

Methods: Prospectively, 60 patients (M:F-31:29) with grade I TBM were recruited. Clinical details were collected; CSF estimation of cytokines, neuropsychological assessment, and correlation were performed.

Results: Mean age at presentation was 32.2 years (32.2 ± 10.1), and the duration of symptoms was 29.9 days (29.9 ± 25.9), respectively. Definitive evidence of mycobacterial infection was observed in 28.3% of the patients. Mean levels of tumor necrosis factor-α (TNF-α), interferon (IFN-γ), and interleukin-6 (IL-6) were 11.57 ± 30.35, 197.02 ± 186.64, and 127.03 ± 88.71 pg/mL, respectively. TNF-α levels were significantly elevated in definitive TBM (p = 0.044). Neuropsychological tests revealed an impaired auditory verbal learning test (88.3%), followed by complex figure test (50%), spatial span test (50%), clock drawing test (48.3%), digit span test (35%), color trail tests 1 and 2 (30% and 33.3%, respectively), and animal naming test (28.3%). Elevated levels of IFN-γ and IL-6 in TBM directly correlated with the number of impaired neuropsychological tests. During follow-up, significant improvement was noticed in animal naming test (p = 0.005), clock drawing test (p = 0.003), color trail test 2 (0.02), spatial span test (p = 0.012), and digit span test (0.035). Verbal learning did not show any significant change. Overall, the neuropsychological tests showed better recovery of attention, working memory, and category fluency and showed minimal recovery of verbal learning.

Conclusions: There is subclinical evidence of cognitive impairment in patients with TBM, and this correlated with elevated cytokines. Both the frontal and temporal lobes showed varying degrees of cognitive impairment.

Figure 1. Comparison of Severity of Neuropsychological Impairment During Baseline and Follow-up (N = 43)

Figure 2. Correlation of Baseline Neuropsychological Tests and Cytokines in all the TBM Cases (N = 60)

IFN-γ = interferon-γ; IL-6 = interleukin-6; TBM = Tuberculous meningitis; TNF-α = tumor necrosis factor-α.