Abstract
Objective
To investigate risk factors associated with long-term mortality in patients with stage II and III tuberculous meningitis (TBM).
Methods
This retrospective analysis examined patients who were first diagnosed with stage II and III TBM at West China Hospital of Sichuan University between January 1, 2018 and October 1, 2019. Patients were followed via telephone and categorized into survival and mortality groups based on 4-year outcomes. Multivariate logistic regression identified independent risk factors for long-term mortality in stage II and III TBM.
Results
In total, 178 patients were included, comprising 108 (60.7%) males and 36 (20.2%) non-survivors. Mean age was 36 ± 17 years. Compared to survivors, non-survivors demonstrated significantly higher age, heart rate, diastolic blood pressure, blood glucose, rates of headache, neurological deficits, cognitive dysfunction, impaired consciousness, hydrocephalus, and basal meningeal inflammation. This group also exhibited significantly lower Glasgow Coma Scale (GCS) scores, blood potassium, albumin, and cerebrospinal fluid chloride. Multivariate analysis revealed age (OR 1.042; 95% CI 1.015–1.070; P = 0.002), GCS score (OR 0.693; 95% CI 0.589–0.814; P < 0.001), neurological deficits (OR 5.204; 95% CI 2.056–13.174; P < 0.001), and hydrocephalus (OR 2.680; 95% CI 1.081–6.643; P = 0.033) as independent mortality risk factors. The ROC curve area under age was 0.613 (95% CI 0.506–0.720; P = 0.036) and 0.721 (95% CI 0.615–0.826; P < 0.001) under GCS score.
Conclusion
Advanced age, reduced GCS scores, neurological deficits, and hydrocephalus were identified as independent risk factors for mortality in stage II and III TBM patients.
Introduction
Tuberculosis (TB) represents a leading cause of infectious disease related deaths globally. TB mortality continues to rise, with untreated cases resulting in up to 50% fatalities [1]. Per the WHO, over 100,000 individuals develop tuberculous meningitis (TBM) annually [2]. As the most severe manifestation of TB, TBM confers substantial neurological morbidity and high mortality. Approximately 80,000 adults were estimated to die from TBM in 2019, with around 30% average mortality [3, 4]. Overall mortality risk reaches 23% by 3 months and 25% by 12 months post-diagnosis [5], with associated disability or death approaching 50% [6,7,8,9]. This confers tremendous personal and public health burden.
Due to ambiguous initial presentation and diagnostic challenges, most TBM patients fail to receive timely intervention [10, 11]. Moreover, many present at later stages of illness (stage II/III) [12, 26]. Peripheral neurological deficits may manifest as hemiplegia, vision or hearing loss, ataxia, unresponsiveness, among others [27, 28]. In our study, 63.9% of long-term deceased patients presented with peripheral neurological symptoms, such as numbness, facial asymmetry, limb weakness, fine motor dysfunction, and urinary and fecal incontinence. These symptoms significantly impaired the patients’ self-care ability and negatively impacted their quality of life, leading to feelings of inferiority, guilt, and loneliness [29]. Quality of life and mental well-being significantly influence disease progression, and strong familial and social support are crucial in enhancing treatment adherence [30]. Therefore, it is essential to mobilize resources for patients diagnosed with advanced TBM to provide psychological support, alleviate negative emotions, and improve their motivation and confidence in adhering to their treatment regimen.
Existing literature suggests a strong association between hydrocephalus and adverse outcomes, including mortality, in TBM patients [31,32,33], particularly those with higher MRC classification. Our study reaffirms these findings. The inflammatory response elicited by mycobacterium tuberculosis infection in the subarachnoid space can lead to a viscous exudate obstructing the subarachnoid space at the brain base, causing hydrocephalus [21]. This common intracranial complication can occur at any stage of TBM and often results in increased intracranial pressure [34]. This may be a primary contributor to elevated intracranial pressure in TBM patients, leading to functional impairments affecting learning, memory, and movement [35], and in severe cases, coma, brain herniation, or death. Head CT/MRI is a reliable tool for diagnosing and assessing the severity of hydrocephalus in TBM patients [36, 37]. Medical professionals should closely monitor imaging results, especially signs of hydrocephalus, in Stage II/III TBM patients. Prompt review of CT or MRI scans is crucial if changes in consciousness level or pupils are observed.
Limitations
The present study has several limitations, including its retrospective design, single-site sampling, reliance on our hospital’s patient records, and relatively small sample size. Future investigations would benefit from a larger sample size and a multi-center, prospective study design.
Conclusions
Age, GCS score, peripheral neurological dysfunction, and hydrocephalus are independent predictors of long-term mortality in advanced TBM patients. Therefore, healthcare professionals should pay close attention to these clinical manifestations, enhance assessment procedures, and provide timely intervention.
Data availability
All data generated or analyzed during this study are included in this article.
Abbreviations
- BMRC:
-
British Medical Research Council
- TB:
-
Tuberculosis
- TBM:
-
Tuberculosis meningitis
- GCS:
-
Glasgow Coma Scale
- SBP:
-
Systolic blood pressure
- DBP:
-
Diastolic blood pressure
- CSF:
-
Cerebrospinal fluid
- OR:
-
Odds ratio
- CI:
-
Confidence interval
- ROC:
-
Receiver Operating Characteristic
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Acknowledgements
We express our gratitude to all the participants for their cooperation.
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Ling Wang conceptualized the study, drafted the manuscript, analyzed the data, and critically revised the manuscript for important intellectual content. Zhihan Gu and **aoli Chen contributed to data analysis. **aomin Yu was involved in the diagnosis and confirmation of tuberculosis meningitis patients. The corresponding author was responsible for study concept design, data analysis and interpretation, manuscript preparation, and intellectual content review. All authors read and approved the final.
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This study was by the Human Ethics Committee of West China Hospital of Sichuan University (Ethics No.: 2018 − 598) and was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants and/or their legal guardian(s). All methods were carried out following the relevant guidelines and regulations.
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Wang, L., Gu, Z., Chen, X. et al. Analysis of risk factors for long-term mortality in patients with stage II and III tuberculous meningitis. BMC Infect Dis 24, 656 (2024). https://doi.org/10.1186/s12879-024-09561-0
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DOI: https://doi.org/10.1186/s12879-024-09561-0