Structural deficits and cognitive impairment in tuberculous meningitis

Abstract

Background: Chronic neuropsychological sequelae may occur in patients with tuberculous meningitis (TBM). The impact of structural abnormalities on the clinical performance of patients with TBM is unknown. This study applied the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) voxel-based morphometry (VBM) to determine if gray matter deficits in TBM are associated with acute presentations and chronic cognitive impairment.

Methods: Seventeen patients with TBM who discontinued their anti-TB therapy for more than six months, and 17 age-, sex-, and education-matched healthy subjects were enrolled. Differences in gray matter volume (GMV) between patients and healthy controls were investigated using DARTEL-VBM to determine structural abnormalities. Disease severity during the acute stage was scored by clinical profiles and conventional imaging findings. Correlations among chronic structural deficits, cognitive impairment, and initial disease severity were assessed.

Results: The patients with TBM had worse neuropsychological subtest performances than the healthy controls. Compared to the controls, the patients showed smaller GMVs in the right thalamus, right caudate nucleus, right superior and middle temporal gyrus, right precuneus, and left putamen (p < 0.001). The smaller GMVs in the right thalamus, right superior temporal gyrus, right precuneus, left putamen, and right caudate nucleus (p < 0.05) were further associated with worse cognitive function. More severe initial disease also correlated with smaller GMVs in the right caudate nucleus (p < 0.05).

Conclusion: Multiple domain cognitive impairment may persist in patients with chronic TBM even after appropriate treatment. Worse initial disease severity may contribute to the vulnerability of brain tissue to damage, with subsequent neuropsychological consequences.

Fig. 1

Results of the VBM comparisons between patients with TBM and healthy controls. On 3D renderings of the brain and representative axial slices through the customized template, patients with TBM had smaller gray matter volumes (GMVs), with highlighted significant areas in the right thalamus, right superior and middle temporal gyrus, right precuneus, and right caudate nucleus

Fig. 2

Significant partial correlations (p < 0.05) were plotted for (a) deep nuclei and (b) cerebral cortex cluster volumes in relation to the NP results (including verbal comprehension, perceptual organization, and working memory). The strongest correlation was between the right thalamus cluster volume and the verbal comprehension index. c In TBM patients, the cluster on the caudate nucleus revealed a significant linear relationship with total disease severity scores based on clinical profiles and conventional MRI findings. Higher total disease severity scores were associated with worse disease conditions and correlated with smaller GMVs in the right caudate nucleus (p < 0.05)