Neurocognitive outcomes of HIV-associated tuberculous meningitis

Carson M Quinn,Mable Kabahubya,Fiona V Cresswell,David R Boulware,David B Meya,John Kasibante,Sarah Lofgren,Alice Namudde,Ananta S Bangdiwala,Noeline Nakasujja,Alison Elliott

doi:10.12688/wellcomeopenres.16967.1

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.

Highlights

Tuberculous meningitis (TBM) continues to incur unacceptably high mortality, especially in people living with HIV, in whom it can exceed 50%1,2
Among the 21 who completed the questionnaire at both time points, moderate and severe depression was present in 17 (81%) at week 8, and 15 (71%) at week 24. In this prospective study of 36 survivors of tuberculous meningitis (TBM) in Uganda, we have reaffirmed the high degree of early functional disability present, demonstrated neurocognitive and functional improvement between two and six months, and described a phenotype of neurocognitive impairment predominantly in executive functioning, information processing speed, and verbal learning and memory
This phenotype is less apparent at eight weeks, when patients are often still recovering from their acute illness and are broadly impaired, but by 24 weeks becomes clear as some neurocognitive domains approach population norms while others remained impaired

Summary

Introduction

Tuberculous meningitis (TBM) continues to incur unacceptably high mortality, especially in people living with HIV, in whom it can exceed 50%1,2. Comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale in 17 TBM patients in Taiwan showed impairment in multiple domains including working memory and verbal comprehension[6] These studies in HIV-negative populations may not be representative of TB-HIV coinfection, as HIV, both independently and in conjunction with TB, contributes to neurocognitive impairment[13,14]; yet, TBM in HIV-infected persons is less inflammatory[15]. 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 clinicianrated functional status. Conclusion: These findings highlight the need for more comprehensive neurocognitive assessment in the survivors of TBM, Invited Reviewers version 1

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Conclusion