Neurocognitive outcomes of tuberculous meningitis in a primarily HIV-positive Ugandan cohort

Abstract

Background: The toll of tuberculous meningitis (TBM) in both mortality and disability is considerable, but advancements in rehabilitation have the potential to improve the functional abilities and the quality of survivors' lives. However, the typical phenotype of neurocognitive impairment in TBM survivors remains unstudied in HIV-predominant populations in sub-Saharan Africa. Methods: We tested 36 survivors of TBM in Uganda with a comprehensive battery of neurocognitive assessments at 8 and 24 weeks after diagnosis, and compared results to a representative cohort of HIV-uninfected Ugandans. Results: While participants had a broad range of impairments at eight weeks, there was marked improvement by 24 weeks, when a phenotype of impairment including deficits in motor functioning, verbal learning and memory, processing speed, and executive function emerged. These deficits were present despite good clinician-rated functional status. The majority (23/27, 85%) had evidence of moderate to severe depression at week 8, and at week 24 (18/24, 75%). Conclusion: These findings highlight the need for more comprehensive neurocognitive assessment in the survivors of TBM, and further investment in and study of rehabilitation, including management of depression, to improve long-term outcomes in this population.

Keywords: HIV; Tuberculous Meningitis; depression; functional; neurocognitive; psychiatric.

Figure 1.. Enrollment in this nested sub-study from the parent randomized RIFT trial.

Figure 2.. Impairment in neurocognitive domains at eight and 24 weeks in survivors of TBM.

Mean cohort Z-scores in each neurocognitive assessment and the summary score (QNPZ-8) at both time points show improvement in most domains. A Z-score <-1 signifies impairment, and a Z-score <-2 signifies severe impairment. Error bars represent standard error. DSF: Digit Span Forward, DSB: Digit Span Backward, AVLT: WHO-UCLA Audio Verbal Learning Test Total, AVLTR: WHO-UCLA Audio Verbal Learning Test Recall, SDM: Symbol Digit Modality, GPB: grooved pegboard, QNPZ-8: Quantitative neurologic performance on eight modalities.

Figure 3.. Proportions of the cohort that are no longer impaired in each assessment at week 24.

Bars approaching 1 signify few participants with impairment in that domain. Majorities of the cohort have impairment in AVLT, AVLTR, SDM, Finger tapping, Color Trails 1, Color Trails 2, Timed Gait, and the summary score (QNPZ-8). Impairment on any given assessment is defined as a Z-score <-1. DSF: Digit Span Forward, DSB: Digit Span Backward, AVLT: WHO-UCLA Audio Verbal Learning Test Total, AVLTR: WHO-UCLA Audio Verbal Learning Test Recall, SDM: Symbol Digit Modality, GPB: grooved pegboard, QNPZ-8: Quantitative neurologic performance on 8 modalities.