Incidence of cranial and ophthalmic nerve palsy and associated risk factors in tuberculous meningitis: A systematic review and meta-regression analysis

Abstract

Background: Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis, frequently complicated by cranial nerve palsy (CNP) and ophthalmic nerve palsy (ONP), which are associated with poor prognosis. Understanding their incidence and associated risk factors is essential for timely diagnosis and improved management. Method: This study conducts a systematic review and meta-analysis of research on CNP and ONP in TBM patients. Several medical databases were searched from the earliest records to April 2025. Eligible studies included cohort studies, cross-sectional studies, case-control studies, and baseline data from clinical trials. Two independent reviewers extracted data and assessed quality. Pooled incidence rates were estimated using random-effects models. Univariable meta-regression explored potential risk factors. Result: Forty-seven diverse studies published between 1977 and 2025 from around the world with varying samples sizes were included. The pooled prevalence of CNP in TBM patients was 26.5 (95 CI: 22.4-31.1 ), while ONP prevalence was 23.9 (95 CI: 18.7-30.0 ). Between-study heterogeneity was substantial. In univariable meta-regression, hydrocephalus was associated with higher incidence of both outcomes, whereas cerebral infarction and higher CSF protein were additionally associated with CNP. These findings represent study-level associations and should be interpreted cautiously. Conclusion: Around one-quarter of TBM patients experience cranial nerve palsy and approximately one-quarter develop ophthalmic nerve palsy. Hydrocephalus emerged as the most consistent correlate of both outcomes. Cerebral infarction and higher CSF protein were also associated with higher CNP incidence. Early identification and management of these complications may improve neurological outcomes, but variability across settings should be interpreted cautiously. Registration number: PROSPERO CRD42025649903