Cerebrospinal Fluid characteristic in Tuberculous Meningitis Patients With and Without Hydrocephalus

Cerebrospinal Fluid characteristic in Tuberculous Meningitis Patients With and Without Hydrocephalus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cerebrospinal Fluid characteristic in Tuberculous Meningitis Patients With and Without Hydrocephalus Paulus Sugianto, Robiah Al Adawiyah This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7017619/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Objective Tuberculous meningitis is the most severe kind of extrapulmonary tuberculosis, impacting around 1–5% of patients with pulmonary tuberculosis globally. Hydrocephalus represents the most common complication, suggest that approximately 80% of TBM patients. This study examined the characteristics of cerebrospinal fluid (CSF) in patients with TBM, with or without hydrocephalus. Methods A retrospective analysis of patient diagnosed with TBM from January 2022 to January 2025 was conducted, collecting demographic details, clinical features, and laboratory results of 39 patients. Patients with TBM diagnosed with CSF Xpert MTB/RIF. Analysis of CSF characteristics and the incidence of TBM with hydrocephalus, using nominal data and the fisher-exact test. Results A total of 39 patients enrolled in this study. Hydrocephalus was noted in 14 (35.9%) of with tuberculous meningitis (TBM). A predominance of lymphocytes greater than 50% in the cerebrospinal fluid (CSF) was identified as a significant characteristic associated with the development of hydrocephalus in TBM. Conclusion Lymphocyte levels exceeding 50% in CSF appear to be a significant predictor of hydrocephalus in patients with tuberculous meningitis. cerebrospinal fluid hydrocephalus meningitis tuberculous meningitis tuberculosis INTRODUCTION Tuberculous meningitis (TBM) is caused by the dissemination of Mycobacterium tuberculosis (MTB) to the meninges, leading to inflammation of the membranes surrounding the brain or spinal cord[ 1 ]. It typically occurs as a disseminated condition resulting from a primary pulmonary tuberculosis infection[ 2 ]. TBM is the most severe form of extrapulmonary tuberculosis, affecting approximately 1–5% of patients with pulmonary tuberculosis worldwide[ 3 ]. The World Health Organization (WHO) estimates that between 30,000 and 490,000 individuals are diagnosed with TBM each year[ 4 ]. Among adult patients, the mortality rate is reported to be as high as 50%, with a significant proportion experiencing long-term neurological sequelae[ 3 ]. Hydrocephalus is the most common complication associated with tuberculous meningitis (TBM). Studies suggest that approximately 80% of TBM patients exhibit ventricular enlargement in the early stages, with hydrocephalus identified as a significant prognostic indicator[ 5 ]. Raut et al. conducted a study involving 80 TBM patients and found that hydrocephalus was present in 65% of cases[ 6 ]. It is a frequent complication and is also associated with poor outcomes[ 7 ]. Hydrocephalus typically presents as elevated intracranial pressure or is detected through imaging techniques[ 8 ]. It is classified into two types: communicating hydrocephalus and non-communicating (obstructive) hydrocephalus . In communicating hydrocephalus, obstruction to cerebrospinal fluid (CSF) flow occurs at the basal cisterns or due to impaired absorption at the arachnoid granulations. In non-communicating hydrocephalus, the obstruction occurs at the cerebral aqueduct or the outflow tract of the fourth ventricle[ 6 ]. Hydrocephalus can be readily diagnosed using CT or MRI scans. MRI is considered the preferred modality for detecting hydrocephalus and for identifying associated features such as tuberculomas, basal exudates, and infarcts[ 6 ]. This study aimed to evaluate the cerebrospinal fluid (CSF) characteristics in TBM patients with and without hydrocephalus. METHODS Study Design This was a retrospective, cross-sectional observational study conducted at a single institution. The study included adult patients with tuberculous meningitis (TBM) who were admitted to the Department of Neurology at Dr. Soetomo Academic Hospital between January 2022 and January 2025. It aimed to evaluate cerebrospinal fluid (CSF) characteristics in TBM patients with and without hydrocephalus. Additionally, clinical characteristics were analysed, including age, gender, disease onset, headache, level of consciousness, neck rigidity, hemiparesis, hyponatremia (serum sodium < 135 mmol/L), and pulmonary TB status. Participants The inclusion criteria for this study were patients aged 18 years or older with a diagnosis of tuberculous meningitis (TBM) confirmed by cerebrospinal fluid (CSF) Xpert MTB/RIF testing. Eligible patients were those who had undergone head imaging using contrast-enhanced CT scans or MRI, routine blood and electrolyte testing, cerebrospinal fluid (CSF) analysis, and chest X-ray examinations. The exclusion criterion was the presence of secondary bacterial infection confirmed through CSF culture. The diagnosis of tuberculous meningitis (TBM) in this study was confirmed using Xpert MTB/RIF[ 4 ]. Xpert MTB/RIF is an automated, cartridge-based polymerase chain reaction (PCR) test that enables rapid diagnostics for tuberculosis. A 2014 review conducted by the World Health Organization (WHO) focusing on TBM determined that Xpert MTB/RIF demonstrates a sensitivity of 80.5% (95% CI 59.0–92.2%) and a specificity of 97.8% (95% CI 95.2–99.0%) as compared to culture results[ 9 ]. Study Methods All subjects in the medical records who met the inclusion and exclusion criteria had their basic demographic data recorded in a structured data collection sheet. Data collection was carried out by two research assistants: one documented the CSF results, while the other compiled the clinical characteristics. Data on clinical features included age, gender, disease onset, headache, level of consciousness, neck rigidity, hemiparesis, hyponatremia (serum sodium < 135 mmol/L), head imaging findings from CT or MRI, and pulmonary TB status. Statistical Analysis Statistical analysis was performed using SPSS version 29.0 (IBM Corp, Armonk, NY, USA). Numerical variables were presented as means and standard deviations, while nominal variables were expressed as counts and percentages. The CSF criteria referenced in this study were based on the Lancet Consensus Scoring System, which includes: clear appearance, cell counts of 10–500/µL, lymphocytic predominance exceeding 50%, protein concentration > 1 g/L, and a CSF-to-plasma glucose ratio 0.5 g/L for analysis. Nominal data were represented using frequency tables and graphical diagrams, while continuous variables were described using mean ± standard deviation. Comparisons of CSF profiles in TBM patients with and without hydrocephalus were analyzed using Fisher’s exact test. A p-value < 0.05 was considered statistically significant. A completed STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for cross-sectional studies is provided as Supplementary Material to ensure adherence to reporting guidelines. RESULTS A total of 72 patients were enrolled in the study; however, 33 were excluded based on the eligibility criteria. Among the remaining 39 patients, 21 (53.8%) were female and 18 (46.2%) were male, with ages ranging from 18 to 57 years. We observed that 28 patients (71.8%) had symptom onset ≥ 5 days prior to admission. Clinical findings included decreased consciousness in 34 patients (87.2%), hyponatremia in 31 (79.5%), headache in 25 (64.1%), nuchal rigidity in 23 (59.0%), pulmonary TB in 19 (48.7%), hydrocephalus in 14 (35.9%), and hemiparesis in 8 (20.5%) (Table 1 ). All patients underwent CSF analysis using the Xpert MTB/RIF assay as the diagnostic tool for TBM. Among the 14 TBM patients with hydrocephalus, 100% had clear CSF appearance, lymphocytic predominance, and cell counts of 10–500/µL. A CSF-to-plasma glucose ratio 0.5 g/L (Table 2 ). A lymphocytic predominance > 50% was found to be significantly associated with hydrocephalus (p = 0.018). DISCUSSION In this study, hydrocephalus was present in 14 (35.9%) of the 39 patients with TBM. All identified cases were of the communicating type. Our findings suggest that a lymphocytic predominance > 50% in CSF is significantly associated with the presence of hydrocephalus ( P = 0.018). To our knowledge, no previous study has directly examined the association between CSF characteristics and hydrocephalus in TBM. However, increased lymphocytic predominance and reduced CSF glucose levels have been consistently linked with TBM. In 2024, Anand et al. reported that hydrocephalus, lymphocyte predominance, and low CSF glucose were significantly associated with positive Xpert MTB/RIF results in TBM patients[ 10 ]. Similarly, a 2023 study by Xiaolin Zhu et al. found that hydrocephalus was more prevalent among elderly TBM patients (≥ 60 years), accompanied by lower CSF glucose and chloride levels, reduced CSF-to-blood glucose ratios, and higher nucleated cell counts[ 11 ]. Table 1 Clinical Characteristics in Patients with Tuberculous Meningitis (n = 39) Demographic Data n(%) Age Mean ± SD Range (year) 31.38±10.747 18–57 Gender Female Male 21 (53.8%) 18 (46.2%) Onset < 5 days ≥5 days 11 (28.2%) 28 (71.8%) Headache 25 (64.1%) Decreased of consciousness 34 (87.2%) Nuchal rigidity 23 (59.0%) Hemiparesis 8 (20.5%) Hyponatremia 31 (79.5%) Pulmonary TB 19 (48.7%) Hydrocephalus 14 (35.9%) Raut et al. conducted a prospective study involving 80 patients and found that vision impairment, cranial nerve palsies, and basal meningeal enhancement were significant predictors of hydrocephalus development over a 6-month follow-up period[ 12 ]. Mycobacterium tuberculosis can form subependymal collections known as Rich foci. These foci may rupture into the subarachnoid space, triggering a severe inflammatory response that manifests as meningitis. The resulting exudates may obstruct CSF flow, leading to hydrocephalus[ 1 ]. Table 2 Cerebrospinal Fluid Characteristics in TBM Patients With and Without Hydrocephalus Features of CSF Meningitis TB, n(%) P -Value a OR (95% CI) With hydrocephalus (n = 14) Without hydrocephalus (n = 25) Clear appearance 14 (100%) 23 (92.0%) 0.405 0.920 (0.820–1.033) Lymphocyte predominant > 50% 14 (100%) 17 (68.0%) 0.018* 0.680 (0.520–0.890) Cells (10–500 /microliter) 14 (100%) 23 (92.0%) 0.405 0.920 (0.820–1.033) Protein > 5 g/L 0 (0%) 2 (8.0%) 0.405 0.920 (0.820–1.033) Glucose CSF:Plasma Ratio < 50% 13 (92.9%) 19 (76.0%) 0.192 0.818 (0.629–1.066) CI: confidence interval a Using fisher-exact test: *p < 0.05 indicates statistical significance Once M. tuberculosis invades the central nervous system, the immune system responds primarily through CD4⁺ T cells (lymphocytes), which secrete interferon-γ and TNF-α to activate macrophages[ 13 ]. A significant lymphocyte presence in CSF is a hallmark of TBM. However, an exaggerated immune response can lead to additional brain injury and worsen clinical symptoms 2 . Initially, CSF may show neutrophil predominance in early TBM, but this pattern typically shifts to lymphocytic dominance as the disease progresses[ 14 ]. LIMITATIONS This study has several limitations. First, the retrospective design and relatively small sample size may have introduced selection bias. Data were obtained solely from medical records, and no long-term patient follow-up was conducted. Additionally, no multivariate analysis was performed to adjust for potential confounders. CONCLUSION Lymphocyte levels exceeding 50% in cerebrospinal fluid are significant predictors of hydrocephalus in patients with tuberculous meningitis. Abbreviations CSF: Cerebrospinal Fluid TBM: Tuberculous Meningitis MTB: Mycobacterium Tuberculosis WHO: World Health Organization CT: Computed Tomography MRI: Magnetic Resonance Imaging PCR: Polymerase Chain Reaction TB: Tuberculosis CI: Confidence Interval Declarations Ethical approval and consent to participate The Ethics Committee of Dr. Soetomo Academic Hospital under approval number 1948/LOE/301.4.2.III/2025. Approved this retrospective study, which involved the anonymous analysis of patient data. This enabled the board to waive the requirement for written informed consent. Consent for publication All authors have approved of and have agreed to submit the manuscript to BMC Neurology and this manuscript has not been published and is not under consideration for publication elsewhere. Availability of data and material The required sample size for estimating sensitivity in a population is calculated using the formulaprovided in the book of Sample Size Determination in Health Studies. https://iris.who.int/handle/10665/40062. Competing interest The authors declare that they have no known competing financial interests or personal relationships to influence the work reported in this paper. Funding The authors declare that no funding was received for this study. Authors’ contributions Conceptualization: PS; Data curation: RAA; Formal analysis: RAA; Methodology: RAA; Software: RAA; Supervision: PS; Validation: PS; Visualization: PS; Writing – original draft: RAA; Writing – review & editing: PS Acknowledgements The authors would like to thank all who have contributed to the process and completion of this report, including the teaching staff of the Department of Neurology of the Faculty of Medicine, UNIVERSITAS AIRLANGGA and Dr. Soetomo Academic Hospital, Surabaya, Indonesia. References Slane VH, Unakal ChG. Tuberculous Meningitis [Internet]. StatPearls [Internet]. 2024 [cited 2024 Oct 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541015/ Manyelo CM, Solomons RS, Walzl G, Chegou NN. Tuberculous Meningitis: Pathogenesis, Immune Responses, Diagnostic Challenges, and the Potential of Biomarker-Based Approaches. Kraft CS, editor. J Clin Microbiol [Internet]. 2021;59. Available from: https://journals.asm.org/doi/10.1128/JCM.01771-20 Milburn J, Ntwayagae O, Ngoni K, Suresh R, Lemme N, Northcott C, et al. The Impact of GeneXpert Cerebrospinal Fluid Testing on Tuberculous Meningitis Diagnosis in Routine Care in Botswana. Open Forum Infect Dis [Internet]. 2024;11. Available from: https://academic.oup.com/ofid/article/doi/10.1093/ofid/ofae489/7743304 Huynh J, Donovan J, Phu NH, Nghia HDT, Thuong NTT, Thwaites GE. Tuberculous meningitis: progress and remaining questions. Lancet Neurol [Internet]. 2022;21:450–64. Available from: www.thelancet.com/neurology Zhang X, Li P, Wen J, Chang J, Chen Y, Yin R, et al. Ventriculoperitoneal shunt for tuberculous meningitis-associated hydrocephalus: long-term outcomes and complications. BMC Infect Dis [Internet]. 2023;23:742. Available from: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08661-7 Paliwal VK, Garg RK. Hydrocephalus in Tuberculous Meningitis - Pearls and Nuances. Neurol India [Internet]. 2021;69:S330–5. Available from: https://journals.lww.com/10.4103/0028-3886.332275 Hasanah NC, Imron A, Ganiem AR. Outcomes of Tuberculous Meningitis Patients with Hydrocephalus with or without Cerebrospinal Fluid Diversion. Althea Med J [Internet]. 2021;8:210–5. Available from: http://journal.fk.unpad.ac.id/index.php/amj/article/view/2300 Pinzon RT, Veronica V. Hydrocephalus Caused by Tuberculous Meningitis in an Immunocompetent Young Adult: A Case Report. Int Med Case Rep J [Internet]. 2023;Volume 16:187–92. Available from: https://www.dovepress.com/hydrocephalus-caused-by-tuberculous-meningitis-in-an-immunocompetent-y-peer-reviewed-fulltext-article-IMCRJ Foppiano Palacios C, Saleeb PG. Challenges in the diagnosis of tuberculous meningitis. J Clin Tuberc Other Mycobact Dis [Internet]. 2020;20:100164. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2405579420300280 Anand RP, Tandon R, Jha S. Clinical, Laboratory and Radiological Correlates of Xpert MTB/RIF Assay Study in Cerebrospinal Fluid in CNS Tuberculosis. Neurol India [Internet]. 2024;72:546–52. Available from: https://journals.lww.com/10.4103/neuroindia.NI_1476_20 Zhu X, He N, Tong L, Gu ZH, Li H. Clinical characteristics of tuberculous meningitis in older patients compared with younger and middle-aged patients: a retrospective analysis. BMC Infect Dis [Internet]. 2023;23:699. Available from: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08700-3 Raut T, Garg RK, Jain A, Verma R, Singh MK, Malhotra HS, et al. Hydrocephalus in tuberculous meningitis: Incidence, its predictive factors and impact on the prognosis. J Infect [Internet]. 2013;66:330–7. Available from: https://linkinghub.elsevier.com/retrieve/pii/S016344531200391X Rock RB, Olin M, Baker CA, Molitor TW, Peterson PK. Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects. Clin Microbiol Rev [Internet]. 2008;21:243–61. Available from: https://journals.asm.org/doi/10.1128/CMR.00042-07 Marais S, Thwaites G, Schoeman JF, Török ME, Misra UK, Prasad K, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis [Internet]. 2010;10:803–12. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1473309910701389 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7017619","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":495931629,"identity":"186e7973-09ae-410c-8252-ccf9e1d384c3","order_by":0,"name":"Paulus Sugianto","email":"data:image/png;base64,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","orcid":"","institution":"Dr Soetomo Academic Hospital","correspondingAuthor":true,"prefix":"","firstName":"Paulus","middleName":"","lastName":"Sugianto","suffix":""},{"id":495931630,"identity":"de508036-7554-4f41-9878-78ca57de774f","order_by":1,"name":"Robiah Al Adawiyah","email":"","orcid":"","institution":"Dr Soetomo Academic Hospital","correspondingAuthor":false,"prefix":"","firstName":"Robiah","middleName":"Al","lastName":"Adawiyah","suffix":""}],"badges":[],"createdAt":"2025-07-01 08:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7017619/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7017619/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88461496,"identity":"f888c9cf-6ea6-40ff-b0b4-0cfe9c0ac780","added_by":"auto","created_at":"2025-08-06 16:36:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":655068,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7017619/v1/ab9addea-8abc-404f-a473-090f0300bfdd.pdf"},{"id":88461014,"identity":"c0482627-b136-4fe9-8471-cd7fd996d011","added_by":"auto","created_at":"2025-08-06 16:28:28","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":87552,"visible":true,"origin":"","legend":"","description":"","filename":"STROBEchecklist.doc","url":"https://assets-eu.researchsquare.com/files/rs-7017619/v1/4310c80338fb2929d2d3b2cb.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cerebrospinal Fluid characteristic in Tuberculous Meningitis Patients With and Without Hydrocephalus","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eTuberculous meningitis (TBM) is caused by the dissemination of \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e (MTB) to the meninges, leading to inflammation of the membranes surrounding the brain or spinal cord[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It typically occurs as a disseminated condition resulting from a primary pulmonary tuberculosis infection[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. TBM is the most severe form of extrapulmonary tuberculosis, affecting approximately 1–5% of patients with pulmonary tuberculosis worldwide[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The World Health Organization (WHO) estimates that between 30,000 and 490,000 individuals are diagnosed with TBM each year[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Among adult patients, the mortality rate is reported to be as high as 50%, with a significant proportion experiencing long-term neurological sequelae[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cb\u003eHydrocephalus\u003c/b\u003e is the most common complication associated with tuberculous meningitis (TBM). Studies suggest that approximately 80% of TBM patients exhibit ventricular enlargement in the early stages, with hydrocephalus identified as a significant prognostic indicator[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Raut et al. conducted a study involving 80 TBM patients and found that hydrocephalus was present in 65% of cases[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. It is a frequent complication and is also associated with poor outcomes[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHydrocephalus typically presents as elevated intracranial pressure or is detected through imaging techniques[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It is classified into two types: \u003cem\u003ecommunicating hydrocephalus and non-communicating (obstructive) hydrocephalus\u003c/em\u003e. In communicating hydrocephalus, obstruction to cerebrospinal fluid (CSF) flow occurs at the basal cisterns or due to impaired absorption at the arachnoid granulations. In non-communicating hydrocephalus, the obstruction occurs at the cerebral aqueduct or the outflow tract of the fourth ventricle[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Hydrocephalus can be readily diagnosed using CT or MRI scans. MRI is considered the preferred modality for detecting hydrocephalus and for identifying associated features such as tuberculomas, basal exudates, and infarcts[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This study aimed to evaluate the cerebrospinal fluid (CSF) characteristics in TBM patients with and without hydrocephalus.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cb\u003eStudy Design\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis was a retrospective, cross-sectional observational study conducted at a single institution. The study included adult patients with tuberculous meningitis (TBM) who were admitted to the Department of Neurology at Dr. Soetomo Academic Hospital between January 2022 and January 2025. It aimed to evaluate cerebrospinal fluid (CSF) characteristics in TBM patients with and without hydrocephalus. Additionally, clinical characteristics were analysed, including age, gender, disease onset, headache, level of consciousness, neck rigidity, hemiparesis, hyponatremia (serum sodium \u0026lt; 135 mmol/L), and pulmonary TB status.\u003c/p\u003e\u003cp\u003e\u003cb\u003eParticipants\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe inclusion criteria for this study were patients aged 18 years or older with a diagnosis of tuberculous meningitis (TBM) confirmed by cerebrospinal fluid (CSF) Xpert MTB/RIF testing.\u003c/p\u003e\u003cp\u003eEligible patients were those who had undergone head imaging using contrast-enhanced CT scans or MRI, routine blood and electrolyte testing, cerebrospinal fluid (CSF) analysis, and chest X-ray examinations. The exclusion criterion was the presence of secondary bacterial infection confirmed through CSF culture.\u003c/p\u003e\u003cp\u003eThe diagnosis of tuberculous meningitis (TBM) in this study was confirmed using Xpert MTB/RIF[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Xpert MTB/RIF is an automated, cartridge-based polymerase chain reaction (PCR) test that enables rapid diagnostics for tuberculosis. A 2014 review conducted by the World Health Organization (WHO) focusing on TBM determined that Xpert MTB/RIF demonstrates a sensitivity of 80.5% (95% CI 59.0–92.2%) and a specificity of 97.8% (95% CI 95.2–99.0%) as compared to culture results[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cb\u003eStudy Methods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll subjects in the medical records who met the inclusion and exclusion criteria had their basic demographic data recorded in a structured data collection sheet. Data collection was carried out by two research assistants: one documented the CSF results, while the other compiled the clinical characteristics. Data on clinical features included age, gender, disease onset, headache, level of consciousness, neck rigidity, hemiparesis, hyponatremia (serum sodium \u0026lt; 135 mmol/L), head imaging findings from CT or MRI, and pulmonary TB status.\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed using SPSS version 29.0 (IBM Corp, Armonk, NY, USA). Numerical variables were presented as means and standard deviations, while nominal variables were expressed as counts and percentages. The CSF criteria referenced in this study were based on the Lancet Consensus Scoring System, which includes: clear appearance, cell counts of 10–500/µL, lymphocytic predominance exceeding 50%, protein concentration \u0026gt; 1 g/L, and a CSF-to-plasma glucose ratio \u0026lt; 50%. Since all samples had protein levels below 1 g/L, the threshold was modified to \u0026gt; 0.5 g/L for analysis.\u003c/p\u003e\u003cp\u003eNominal data were represented using frequency tables and graphical diagrams, while continuous variables were described using mean ± standard deviation. Comparisons of CSF profiles in TBM patients with and without hydrocephalus were analyzed using Fisher’s exact test. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\u003cp\u003e A completed STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist for cross-sectional studies is provided as Supplementary Material to ensure adherence to reporting guidelines.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 72 patients were enrolled in the study; however, 33 were excluded based on the eligibility criteria. Among the remaining 39 patients, 21 (53.8%) were female and 18 (46.2%) were male, with ages ranging from 18 to 57 years. We observed that 28 patients (71.8%) had symptom onset\u0026thinsp;\u0026ge;\u0026thinsp;5 days prior to admission. Clinical findings included decreased consciousness in 34 patients (87.2%), hyponatremia in 31 (79.5%), headache in 25 (64.1%), nuchal rigidity in 23 (59.0%), pulmonary TB in 19 (48.7%), hydrocephalus in 14 (35.9%), and hemiparesis in 8 (20.5%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAll patients underwent CSF analysis using the Xpert MTB/RIF assay as the diagnostic tool for TBM. Among the 14 TBM patients with hydrocephalus, 100% had clear CSF appearance, lymphocytic predominance, and cell counts of 10\u0026ndash;500/\u0026micro;L. A CSF-to-plasma glucose ratio\u0026thinsp;\u0026lt;\u0026thinsp;50% was found in 13 patients (92.9%). None of the hydrocephalus patients had a CSF protein concentration\u0026thinsp;\u0026gt;\u0026thinsp;0.5 g/L (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). A lymphocytic predominance\u0026thinsp;\u0026gt;\u0026thinsp;50% was found to be significantly associated with hydrocephalus (p\u0026thinsp;=\u0026thinsp;0.018).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, hydrocephalus was present in 14 (35.9%) of the 39 patients with TBM. All identified cases were of the communicating type. Our findings suggest that a lymphocytic predominance\u0026thinsp;\u0026gt;\u0026thinsp;50% in CSF is significantly associated with the presence of hydrocephalus (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018). To our knowledge, no previous study has directly examined the association between CSF characteristics and hydrocephalus in TBM.\u003c/p\u003e\u003cp\u003eHowever, increased lymphocytic predominance and reduced CSF glucose levels have been consistently linked with TBM. In 2024, Anand et al. reported that hydrocephalus, lymphocyte predominance, and low CSF glucose were significantly associated with positive Xpert MTB/RIF results in TBM patients[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Similarly, a 2023 study by Xiaolin Zhu et al. found that hydrocephalus was more prevalent among elderly TBM patients (\u0026ge;\u0026thinsp;60 years), accompanied by lower CSF glucose and chloride levels, reduced CSF-to-blood glucose ratios, and higher nucleated cell counts[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical Characteristics in Patients with Tuberculous Meningitis (n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDemographic Data\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en(%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\u003cp\u003eRange (year)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31.38\u0026plusmn;10.747\u003c/p\u003e\u003cp\u003e18\u0026ndash;57\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003cp\u003eFemale\u003c/p\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (53.8%)\u003c/p\u003e\u003cp\u003e18 (46.2%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOnset\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u0026lt;\u0026thinsp;5 days\u003c/p\u003e\u003cp\u003e\u0026ge;5 days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (28.2%)\u003c/p\u003e\u003cp\u003e28 (71.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHeadache\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25 (64.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDecreased of consciousness\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e34 (87.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNuchal rigidity\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23 (59.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHemiparesis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8 (20.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHyponatremia\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e31 (79.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePulmonary TB\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19 (48.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHydrocephalus\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (35.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eRaut et al. conducted a prospective study involving 80 patients and found that vision impairment, cranial nerve palsies, and basal meningeal enhancement were significant predictors of hydrocephalus development over a 6-month follow-up period[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e can form subependymal collections known as Rich foci. These foci may rupture into the subarachnoid space, triggering a severe inflammatory response that manifests as meningitis. The resulting exudates may obstruct CSF flow, leading to hydrocephalus[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCerebrospinal Fluid Characteristics in TBM Patients With and Without Hydrocephalus\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eFeatures of CSF\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eMeningitis TB, n(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e-Value\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eWith hydrocephalus (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eWithout hydrocephalus (n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClear appearance\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23 (92.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.405\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.920\u003c/p\u003e\u003cp\u003e(0.820\u0026ndash;1.033)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymphocyte predominant\u0026thinsp;\u0026gt;\u0026thinsp;50%\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e17 (68.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.018*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.680\u003c/p\u003e\u003cp\u003e(0.520\u0026ndash;0.890)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCells (10\u0026ndash;500 /microliter)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (100%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23 (92.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.405\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.920\u003c/p\u003e\u003cp\u003e(0.820\u0026ndash;1.033)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eProtein\u0026thinsp;\u0026gt;\u0026thinsp;5 g/L\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (8.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.405\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.920\u003c/p\u003e\u003cp\u003e(0.820\u0026ndash;1.033)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGlucose CSF:Plasma Ratio\u0026thinsp;\u0026lt;\u0026thinsp;50%\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (92.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19 (76.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.192\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.818\u003c/p\u003e\u003cp\u003e(0.629\u0026ndash;1.066)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eCI: confidence interval\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003eUsing fisher-exact test: *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicates statistical significance\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eOnce \u003cem\u003eM. tuberculosis\u003c/em\u003e invades the central nervous system, the immune system responds primarily through CD4⁺ T cells (lymphocytes), which secrete interferon-γ and TNF-α to activate macrophages[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. A significant lymphocyte presence in CSF is a hallmark of TBM. However, an exaggerated immune response can lead to additional brain injury and worsen clinical symptoms\u003csup\u003e2\u003c/sup\u003e. Initially, CSF may show neutrophil predominance in early TBM, but this pattern typically shifts to lymphocytic dominance as the disease progresses[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cb\u003eLIMITATIONS\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, the retrospective design and relatively small sample size may have introduced selection bias. Data were obtained solely from medical records, and no long-term patient follow-up was conducted. Additionally, no multivariate analysis was performed to adjust for potential confounders.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eLymphocyte levels exceeding 50% in cerebrospinal fluid are significant predictors of hydrocephalus in patients with tuberculous meningitis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCSF:\u003c/em\u003e\u003c/strong\u003e Cerebrospinal Fluid\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTBM:\u003c/em\u003e\u003c/strong\u003e Tuberculous Meningitis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMTB:\u003c/em\u003e\u003c/strong\u003e Mycobacterium Tuberculosis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eWHO:\u003c/em\u003e\u003c/strong\u003e World Health Organization\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCT:\u003c/em\u003e\u003c/strong\u003e Computed Tomography\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMRI:\u003c/em\u003e\u003c/strong\u003e Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePCR:\u003c/em\u003e\u003c/strong\u003e Polymerase Chain Reaction\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTB:\u003c/em\u003e\u003c/strong\u003e Tuberculosis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCI:\u003c/em\u003e\u003c/strong\u003e Confidence Interval\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe Ethics Committee of Dr. Soetomo Academic Hospital under approval number 1948/LOE/301.4.2.III/2025. Approved this retrospective study, which involved the anonymous analysis of patient data. This enabled the board to waive the requirement for written informed consent.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eAll authors have approved of and have agreed to submit the manuscript to BMC Neurology and this manuscript has not been published and is not under consideration for publication elsewhere.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and material\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe required sample size for estimating sensitivity in a population is calculated using the formulaprovided in the book of Sample Size Determination in Health Studies.\u0026nbsp;https://iris.who.int/handle/10665/40062.\u003c/p\u003e\n\u003ch2\u003eCompeting interest\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships to influence the work reported in this paper.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThe authors declare that no funding was received for this study.\u003c/p\u003e\n\u003ch2\u003eAuthors’ contributions\u003c/h2\u003e\n\u003cp\u003eConceptualization: PS; Data curation: RAA; Formal analysis: RAA; Methodology: RAA; Software: RAA; Supervision: PS; Validation: PS; Visualization: PS; Writing – original draft: RAA; Writing – review \u0026amp; editing: PS\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eThe authors would like to thank all who have contributed to the process and completion of this report, including the teaching staff of the Department of Neurology of the Faculty of Medicine, UNIVERSITAS AIRLANGGA and Dr. Soetomo Academic Hospital, Surabaya, Indonesia.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSlane VH, Unakal ChG. Tuberculous Meningitis [Internet]. StatPearls [Internet]. 2024 [cited 2024 Oct 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK541015/\u003c/li\u003e\n\u003cli\u003eManyelo CM, Solomons RS, Walzl G, Chegou NN. Tuberculous Meningitis: Pathogenesis, Immune Responses, Diagnostic Challenges, and the Potential of Biomarker-Based Approaches. Kraft CS, editor. J Clin Microbiol [Internet]. 2021;59. Available from: https://journals.asm.org/doi/10.1128/JCM.01771-20\u003c/li\u003e\n\u003cli\u003eMilburn J, Ntwayagae O, Ngoni K, Suresh R, Lemme N, Northcott C, et al. The Impact of GeneXpert Cerebrospinal Fluid Testing on Tuberculous Meningitis Diagnosis in Routine Care in Botswana. Open Forum Infect Dis [Internet]. 2024;11. Available from: https://academic.oup.com/ofid/article/doi/10.1093/ofid/ofae489/7743304\u003c/li\u003e\n\u003cli\u003eHuynh J, Donovan J, Phu NH, Nghia HDT, Thuong NTT, Thwaites GE. Tuberculous meningitis: progress and remaining questions. Lancet Neurol [Internet]. 2022;21:450\u0026ndash;64. Available from: www.thelancet.com/neurology\u003c/li\u003e\n\u003cli\u003eZhang X, Li P, Wen J, Chang J, Chen Y, Yin R, et al. Ventriculoperitoneal shunt for tuberculous meningitis-associated hydrocephalus: long-term outcomes and complications. BMC Infect Dis [Internet]. 2023;23:742. Available from: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08661-7\u003c/li\u003e\n\u003cli\u003ePaliwal VK, Garg RK. Hydrocephalus in Tuberculous Meningitis - Pearls and Nuances. Neurol India [Internet]. 2021;69:S330\u0026ndash;5. Available from: https://journals.lww.com/10.4103/0028-3886.332275\u003c/li\u003e\n\u003cli\u003eHasanah NC, Imron A, Ganiem AR. Outcomes of Tuberculous Meningitis Patients with Hydrocephalus with or without Cerebrospinal Fluid Diversion. Althea Med J [Internet]. 2021;8:210\u0026ndash;5. Available from: http://journal.fk.unpad.ac.id/index.php/amj/article/view/2300\u003c/li\u003e\n\u003cli\u003ePinzon RT, Veronica V. Hydrocephalus Caused by Tuberculous Meningitis in an Immunocompetent Young Adult: A Case Report. Int Med Case Rep J [Internet]. 2023;Volume 16:187\u0026ndash;92. Available from: https://www.dovepress.com/hydrocephalus-caused-by-tuberculous-meningitis-in-an-immunocompetent-y-peer-reviewed-fulltext-article-IMCRJ\u003c/li\u003e\n\u003cli\u003eFoppiano Palacios C, Saleeb PG. Challenges in the diagnosis of tuberculous meningitis. J Clin Tuberc Other Mycobact Dis [Internet]. 2020;20:100164. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2405579420300280\u003c/li\u003e\n\u003cli\u003eAnand RP, Tandon R, Jha S. Clinical, Laboratory and Radiological Correlates of Xpert MTB/RIF Assay Study in Cerebrospinal Fluid in CNS Tuberculosis. Neurol India [Internet]. 2024;72:546\u0026ndash;52. Available from: https://journals.lww.com/10.4103/neuroindia.NI_1476_20\u003c/li\u003e\n\u003cli\u003eZhu X, He N, Tong L, Gu ZH, Li H. Clinical characteristics of tuberculous meningitis in older patients compared with younger and middle-aged patients: a retrospective analysis. BMC Infect Dis [Internet]. 2023;23:699. Available from: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08700-3\u003c/li\u003e\n\u003cli\u003eRaut T, Garg RK, Jain A, Verma R, Singh MK, Malhotra HS, et al. Hydrocephalus in tuberculous meningitis: Incidence, its predictive factors and impact on the prognosis. J Infect [Internet]. 2013;66:330\u0026ndash;7. Available from: https://linkinghub.elsevier.com/retrieve/pii/S016344531200391X\u003c/li\u003e\n\u003cli\u003eRock RB, Olin M, Baker CA, Molitor TW, Peterson PK. Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects. Clin Microbiol Rev [Internet]. 2008;21:243\u0026ndash;61. Available from: https://journals.asm.org/doi/10.1128/CMR.00042-07\u003c/li\u003e\n\u003cli\u003eMarais S, Thwaites G, Schoeman JF, T\u0026ouml;r\u0026ouml;k ME, Misra UK, Prasad K, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis [Internet]. 2010;10:803\u0026ndash;12. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1473309910701389\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"cerebrospinal fluid, hydrocephalus, meningitis, tuberculous meningitis, tuberculosis","lastPublishedDoi":"10.21203/rs.3.rs-7017619/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7017619/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTuberculous meningitis is the most severe kind of extrapulmonary tuberculosis, impacting around 1\u0026ndash;5% of patients with pulmonary tuberculosis globally. Hydrocephalus represents the most common complication, suggest that approximately 80% of TBM patients. This study examined the characteristics of cerebrospinal fluid (CSF) in patients with TBM, with or without hydrocephalus.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective analysis of patient diagnosed with TBM from January 2022 to January 2025 was conducted, collecting demographic details, clinical features, and laboratory results of 39 patients. Patients with TBM diagnosed with CSF Xpert MTB/RIF. Analysis of CSF characteristics and the incidence of TBM with hydrocephalus, using nominal data and the fisher-exact test.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 39 patients enrolled in this study. Hydrocephalus was noted in 14 (35.9%) of with tuberculous meningitis (TBM). A predominance of lymphocytes greater than 50% in the cerebrospinal fluid (CSF) was identified as a significant characteristic associated with the development of hydrocephalus in TBM.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eLymphocyte levels exceeding 50% in CSF appear to be a significant predictor of hydrocephalus in patients with tuberculous meningitis.\u003c/p\u003e","manuscriptTitle":"Cerebrospinal Fluid characteristic in Tuberculous Meningitis Patients With and Without Hydrocephalus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-06 16:20:23","doi":"10.21203/rs.3.rs-7017619/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-08-22T17:11:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-15T06:01:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"91227773800798343827910777756901532053","date":"2025-08-11T17:30:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-11T07:51:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"67713454175402293400475068956253176921","date":"2025-08-11T05:47:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"308020311345498254181499274231708515819","date":"2025-08-07T09:15:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-04T18:01:28+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-04T16:43:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-03T23:18:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-03T23:18:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-07-01T07:59:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e30effec-5697-4a7f-b85c-946c82b80b08","owner":[],"postedDate":"August 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-08-06T16:20:23+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-06 16:20:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7017619","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7017619","identity":"rs-7017619","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}